Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524152EnglishN2013January26General SciencesURBAN INDUSTRIALIZATION IS A CAUSE FOR MIGRATION: AN EVIDENCE FROM NORTH - KARNATAKA
English0107Guruprasad GaneshkarEnglish Rama B. GoudaEnglishIndustrialization is used as synonym for the development and might also be used for urbanization which creates a wide range of job, business trade opportunities in urban areas. Industrialization in urban areas is leading the rural people to migrate to urban area and there are various reasons for migration. In this connection, an attempt is made in this paper is to analyze the reasons or causes for migration of rural people to urban areas, mainly to industrial sector. With this background, the main objective of the present study is to understand the role and impact of urbanization in migration of rural poor to urban areas. As the study is based on primary data, 220 labours working in different types of industries were interviewed. The present study has been undertaken in Belgaum District of North Karnataka, which is considered as less developed compared to South Karnataka in Karnataka state. This study found that the employment (in industries) related reasons had led the rural people to migrate to urban areas.
EnglishLabours, Migration, Industrialization, Urbanization, Employment.INTRODUCTION
In a over populated and developing country, like ours, Industrial development play a vital role in the upliftment of the region. The Government, at the Centre had made a clear announcement of the importance of this sector which is utilizing the massive manpower in both the rural and urban areas. Urban industrialization generally can be defined as the development of all kind of industries in the urban area. It contributes and helps in the involvement and empowerment of common people by demolishing the geographical boundaries. It leads to an equitable distribution of employment opportunities and helps in reducing inequality in per capita income among different regions. Urban industrialization has generated opportunities for the employment seekers and is also attracting rural people to urban areas. Hence, it helps to check rural-urban migration. Thus the present paper attempts to know the impact and role of urban industrialization, which is leading to migration of people from rural areas to urban areas.
Meaning of Migrant
An individual or household member whose last usual place of residence (UPR), anytime in the past, was different from the present place of enumeration was considered as a migrant member in a household. (NSSO, 2011).
Review of Literature
NSS 64th ROUND (2010), in its study found that, rural people are migrating towards urban areas and nearly 67 per cent of households have migrated to urban areas. Mainly these people are been migrated for employment related reasons. Ram B. Bhagat (2005 and 2011), revealed that the rural poor mainly migrate to the near by towns and cities and not mainly to metros. This is due to enormous increase in the cost of living in metros and some big cities. As the rural poor get low wages in subsistence sector in rural areas, are migrating to near by towns and cities which are industrially developing. A huge number of new towns emerged during the last decade with development in basic amenities are attracting rural poor to urban areas. Subhash Chandra Garg (2005), Massive development in the urban infrastructure services had boosted the economics activities in the urban areas. And it has led for the development of industrial and service sectors in those areas. This has in turn increased the employment opportunities in urban areas. Hence, overall development leads to the migration of people from rural to urban areas. Thus number of studies mentioned different types of reasons or causes for migration of rural population to urban areas. In particular to Belgaum district there is no any particular study to relation to the impact of urbanization (industrialization) on rural to urban migration. In this connection, the main objective of this paper is to analyze the causes for migration of rural people to urban areas, mainly to industrial sector.
DATABASE AND METHODOLOGY
The present study is based on both primary and secondary data. Primary data is collected from labours or workers from different industries located in Belgaum city of Karnataka state. Belgaum city falls in North Karnataka was selected for the present study. North Karnataka is considered as less developed compared to South Karnataka as reported by “High Powered Committee on Regional Imbalance and Redressal in Karnataka’ (2002). The selected city which is a large district place having wide industrial base in North Karnataka, with continuously increasing urban population since past two decades. 220 samples were selected from different industry sectors like manufacturing, construction, transport and garments industries in Belgaum city for this case study. The structured schedules were used to collect the relevant data from the labours (migrated people) in different industries. To make the study reliable and efficient equal number of respondents were selected from manufacturing (55), construction (55), transport (55) and garments (55) industries for the present study. Simple statistical tools like percentages, averages etc. were computed to make comparative study and needful analysis. With the above database and methodology the present study mainly concentrates to find the various reasons for migration of people (labours) from rural to Urban Area
. RESULTS AND DISCUSSION
Many studies have mentioned different types of causes or reasons for migration of rural people to urban areas. In this section an attempt is being made to analyze and discuss the various causes and reasons that lead and sometime force the rural people (labours/workers) to migrate to urban areas. With the sample size of 220 respondents, here the extent of impact of urban industrialization on rural workers/peoples migration to urban area (Belgaum) is analyzed and discussed with the help of table no-1. The causes or reasons for migration are subdivided into two sub aspects they are A) Employment or Industry Related Reasons and B) Other SocioEconomic Reasons. These reasons are explained with the help of Table no.1 and discussed in detail below. And the following discussion shows that the employment or industry related reasons (69.1%) to a large extent had led for the migration of rural people to urban area (Belgaum) from their native. And 30.9% of respondents have revealed the socioeconomic reasons for their migration to urban area. Hence, analysis and discussion made below shows the vital causes for the migration of people from rural to urban area (Belgaum).
REASON FOR MIGRATION
Table no-1 shows the different reasons revealed by the respondents for their migration from rural to urban areas. With the help of results in the table following analysis and discussion is being made
A. Employment or Industry related reasons or causes Employment or industry related reasons are the reasons putforth by the respondents which shows that, people migrated to urban area (Belgaum) in search of employment in industries, in search of business opportunities, to enhance their skills and others which are discussed below. i) In search of direct employment in industries: Total of 19.5(43) percent of respondents proposed that they have migrated to Belgaum city in search of direct employment in industries. Where as 21.8 percent (12), 16.4percent (9) and 23.6 percent (13) of respondents from manufacturing, Construction, and Garments industries mentioned the same cause or reason for there migration
. ii) In search of better employment : People who were working in agriculture field and allied activities where their wages were low, due to this dissatisfaction they had come to the city of enumeration in search of better employment, in terms of emoluments, job satisfaction, etc. Respondents from Manufacturing (14.5 percent), Construction (21.8 percent), Transport (10.9 percent) and Garments (14.5 percent) have give this reason for their migration to urban area. This shows that wage level in rural areas is below satisfaction point. However total of 15.5 percent (34) of total respondents had given this reason for their migration to Belgaum city.
iii) In search of Business opportunities: Table 1 depicts that people had migrated to start a new business in city. Thus out of 220 respondents 6.4 percent of respondents revealed this as the important cause for their migration. From transport industry 16.4 percent (9) respondents have revealed their interest of undertaking their business. Whereas only 3.6 percent (2) respondents from Manufacturing and construction industry shown equal interest for the same.
iv) Expectation of higher Income/ Wage level: Another important cause or reason for migration from rural to urban is the people’s expectation of higher Income/ Wage level in urban area. 21.8 percent (12) of respondents from Transport industries, 20.0 percent (11) from Garment industry, 12.7 percent (07) of Construction and remaining 10.9 percent (06) from manufacturing industry respondents migrated to Belgaum city due to the Expectation of higher Income/ Wage level.
v) To Enhance Skill and experience for self employment: For the purpose of their skill development and experience the respondents are working in different industry sectors, so that after enhancement of their skill and experience they want to be self employed. 5.5 percent (3)from both manufacturing and Construction, and 1.8percent (1) and 3.6 percent(2) of respondents from Transport and Garments industries respectively mentioned the same cause for their migration.
vi) Transfer of service/ contract: Transfer of service/ contract included persons who as part of the employment contract or service liability migrate from one place of posting to another. 9.1 percent (5) respondents from Transport industries, 10.9 percent (06) from Garment industry, 3.6 percent (02) of Construction and remaining 5.5 percent (03) from manufacturing industry respondents migrated to Belgaum city due to transfer of service or contract of job.
B. Other Socio-Economic Causes or Reasons which lead to Migration:
There are some socio-economic factors or causes that led for migration of rural people to urban area. These causes or reasons are discussed briefly below with the help of Table -1.
iii. Natural disaster (drought, flood, tsunami, etc) : 9.1 percent of respondents from manufacturing, 7.3 percent, 1.8 percent and 5.5 percent from construction, transport and garments industry had migrated due to natural disaster caused by earthquake, drought, flood, cyclone, tsunami, etc., were covered under this category. Where as, total of 5.9 percent of respondents have migrated from rural due to this reason.
iv. Social / political problems (riots, terrorism, political refugee, bad law and order, etc.) are also one o f the important cause for migration from rural to urban i.e Belgaum. Only 3 respondents (1.4%) had given this as the reason for their migration to urban areas.
v. Displacement by development project: Sometime undertaking development projects, such as construction of dams, power plants, or starting a new factory, etc., might result in eviction of persons and those affected by such displacements may migrate to other village/ town. Such types of migration were included in this category. 07 respondents have migrated due to this cause in Almatti of Bagalkot district. 7.2 percent of respondents out of 220 respondents had migrated due to this reason.
vi. Children Education / Studies: For the purpose of their children’s higher education some of the respondents are migrated to Belgaum city. 5.9 percent (13) respondents revealed this cause or reason for their migration to Belgaum.
vii. Housing Problems: Certain persons moved from their natives or rural areas to Belgaum due to the problems of getting suitable accommodation, poor amenities in rural areas etc. 5.0 percent (11) of total respondents have mentioned this cause as the reason for their migration.
viii. Health Care: Persons sometimes moved from one place to another due to the availability of better medical facilities for treatment or conditions in urban city. And due to this factor cause or reason 5.0 percent (11) of total respondents migrated to urban area i.e. Belgaum.
ix. Migration of parent/ earning member of the family: Sometimes the family members, parent or earning member of the family were passive movers form their village or rural area to urban area. 4.1 percent (9) respondents have given this as the cause for their migration. Thus after analyzing the above table-1 it is found that the employment and business opportunities in different industrial sectors of Belgaum urban area motivate the people to migrate from nearby urban area i.e. Belgaum.
Respondents plan for Migration
With the help of Table no-2 respondents plan for migration is discussed. This shows the extent to which the respondents migrated to urban area (Belgaum) i.e, whether migration is permanent or yet they are planning to migrate or not migrating permanently. From the study it was found that more than 50 percent respondents had completely migrated to urban area (Belgaum). From table-2 it is found that 51.8 percent (114) respondents have already settled in Belgaum city, where as among them 56.4 percent (31) respondents from Garments industry, 52.7 percent (29), 36.4 percent (20) and 61.8 percent (34) respondents from construction, transport and garments have already or permanently settled i.e. migrated to Belgaum urban area. Mainly Garments (61.8 percent) and manufacturing (56.4 percent) have to a large extent migrated. In case of people who are temporarily settled/migrated in Belgaum are about 38.2 percent (21), 25.5 percent (14), 21.8 percent (12) and 20.0(11) from construction, manufacturing, transport and garment industries respectively. 14.5 percent (32) of the total respondents revealed that they are migrating completely only after getting permanent job in some industry or any kind of business in Belgaum urban area. Among These respondents majority of them were from transport (27.3 percent) and Garments (14.5 percent). 7.3 percent (16) of the respondents are not planning to settle or migrate in Belgaum and they are going back to their native villages. From the above analysis it is found that majority of the respondents are supposed to settle in Belgaum urban city.
SUGGESTIONS
Migration from rural to urban is acceptable from the point of rural people’s expectation for higher wages in urban areas. But migration from rural to urban is not good from the point of view of rural economy, as rural agriculture and their allied activities will be affected severely. Hence, few suggestion are put forth here which could control the migration or which could lead to limited migration from rural to urban areas. ? Increasing the employment/ job/business opportunities in rural areas through promotion and development of micro, cottage and small industries in rural areas. ? Agriculture should be developed providing new technologies, so that enough production or income from this sector would not lead to migration of rural people. And along with the agriculture, its allied activities need to be promoted and developed. These allied activities are the best source of income generating activities to the rural people. ? Development of infrastructural and basic amenities like health, sanitation, education, transport, communication, ICT etc in rural areas. Increasing the trade opportunities in rural areas is also necessary. ? Providing financial assistance, functional and vocational training, entrepreneurship development training to the young generation to start up their own enterprises or ventures like cottage and micro industries, stationary or petty shops etc. Hence, Government should also take necessary measures in relation to above discussed suggestion by framing and implementing new policies and programmes.
CONCLUSION
The present study made an attempt to understand the role of industrialization in urban areas which has led to migration of rural people to urban areas. As industrialization has led to increase in wage levels of labours which is more than or above subsistence level (as it is very low in rural agricultural). Higher employment, business opportunities and development of infrastructural, basic amenities in urban areas caused for the migration of rural people/labours to urban areas.
ACKNOWLEDGEMENT
We authors are thankful to all the researchers and authors of whom we have made references for their significant contributions in connection with SSI sector. And we are also grateful to IJCRR editorial board members, team of reviewers who have helped us to bring quality to this present paper
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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524152EnglishN-0001November30General SciencesPHYTOCHEMISTRY, ANTIOXIDANT AND ANTIBACTERIAL ACTIVITIES OF MEDICINAL PLANTS- A COMPARATIVE STUDY
English0819Rajamurugan R.English Deepa V.English Sivashanmugam M.English Raghavan C. M.EnglishPlants are the most important sources of medicines. Today the large number of drugs in use is derived from plants. The important advantages for therapeutic uses of medicinal plants in various ailments are their safety besides being economical, effective and easy availability. The present investigation was aimed to screen phytochemicals, antioxidant and antibacterial activities of ethanolic extracts of leaves of Aegle marmelos, Ocimum sanctum, Alternanthera sessilis, Eclipta alba, and Acalypha indica. The phytochemical analysis revealed the presence of terpenoids, phenols, flavonoids, tannins, alkaloids, cardiac glycosides, and steroids in all the extracts. The antioxidant activity of the extracts was evaluated by DPPH, ABTS and reducing power assay. All the extracts showed significant antioxidant activity. The plant preparations were also screened individually for antibacterial activity against three selected bacterial sp by agar-well diffusion method. Results showed that all the extracts were effective against bacterial sp tested.
EnglishAegle marmelos, Ocimum sanctum, Alternanthera sessilis, Antioxidant activity, Antimicrobial activity.INTRODUCTION
Current advancements in drug discovery technology and search for novel chemical diversity have intensified the efforts for exploring leads from Ayurveda, the traditional system of medicine in India. Ayurvedic system of medicine has its long history of therapeutic potential. The use of plant extracts and phytochemicals both with known antimicrobial properties is of great significance, in the past few years several investigations have been conducted worldwide to prove antioxidant and antimicrobial activities from medicinal plants (Alonso-Paz et al., 1995; Nascimento et al., 1990). For a long period of time, plants have been a valuable source of natural products for maintaining human health, especially in the last decade, with more intensive studies for natural therapies (Sukanya et al., 2009). The medicinal plants are rich in secondary metabolites which are potential sources of drugs (Nadeem et al., 2010). It has been reported the free radical scavenging and antimicrobial activity of many medicinal plants are responsible for therapeutic effects against cancer, inflammatory, cardiovascular and infectious diseases. Since the use of medicinal plants have seconded a wide range in treating diseases, the present study concentrates on antioxidant and antibacterial activities of commonly available medicinal plants Aegle marmelos, Ocimum sanctum, Alternanthera sessilis, Eclipta alba, and Acalypha indica. Aegle marmelos (L) (Rutaceae) is growing wild throughout deciduous forest of India. Its fruits and leaves are valued in indigenous medicine (Charakbraty et al., 1960). The plant has been employed for long time in folk therapy. Poultice made of leaves are used for ophthalmia and ulcers. The leaves are use to lowering the blood glucose levels (Ayurvedic Pharmacopoeia of India, 1988). Other actions like antifungal (Renu, 1983), antibacterial (Banerji and Kumar, 1980), antiprotozoal (Banerjee, 1980), antispermatogenic (Sur et al, 1999) are also reported. Ocimum sanctum Linn. (Labiatae), commonly known as holy basil, is an herbaceous plant found throughout the South Asian region (Hannan et al 2007). The oil of Ocimum sanctum possesses antibacterial, antifungal, antioxidant and radioprotective properties (Sharma et al., 2002). Ancient Hindu literature is rich with the medical actions of Ocimum sanctum (Ubiad et al., 2002). Alternanthera sessilis is a prostrate or perennial herb. The branches are raised from the root and are up to 50 cm long. This plant is found in damp places, wet headlands, roadsides and sometimes as weed of plantations. In South East Asia this plant is taken as vegetables. In India it is used for treatment of gastrointestinal problems (Archana et al., 2011). Eclipta alba L. Hassk. (Asteraceae) has been reported for treating liver was cirrhosis and infective hepatitis (Chopra et al., 1966). In Ayurveda, the root powder is used for viz. treating hepatitis, enlarged spleen and skin disorders. Mixed with a little oil when applied to the head, the herb relieves headache. The extract of its leaves is mixed honey and given to infants, for to expel worms. Eclipta alba is also given to children in case of urinary tract infections (Prabu et al., 2011). Acalypha indica belongs to the family Euphorbiaceae. The leaf can be used for the treatment of throat infections and wound healing, and also used as anti-venom and migraine pain relief. (Oudhia, 2003; Valsara, 1994).
MATERIALS AND METHODS
Extraction of plant material
The plant materials (Aegle marmelos (AM), Ocimum sanctum (OS), Alternanthera sessilis (AS) Eclipta alba (EA), and Acalypha indica (AI)) were collected locally. Authentication of the plant materials was made by Dr.M.Shivashanmugam, Asst professor in Botany, M.G.R College, Hosur. Leaves were detached and dried in shade. About 100 gms of dried leaves were ground to powder and exhaustively extracted with 600 ml ethanol separately using soxhlet apparatus and extracts were concentrated under reduced pressure and then stored in an air tight container for further study.
Phytochemical screening
Phytochemical screening was performed using standard procedures (Sofowora et al., 1993; Trease, 1989).
Evaluation of antioxidant activity
DPPH radical scavenging assay The free radical scavenging activity of all the extracts was measured by decrease in the absorbance of ethanolic solution of DPPH (Braca et al., 2001). Different concentration of extracts (10-500 µg/ml) and positive control ascorbic acid was added to 2 ml of freshly prepared DPPH. The measurement was performed in triplicates. After incubation for about 30 min at room temperature in the dark, the absorbance was measured at 520 nm using spectrophotometer (RAYLEIGH).
Radical scavenging activity (%) was calculated using the following formula:-
ABTS radical cation-scavenging activity
The antioxidant activities of extracts were determined by the improved ABTS. + radical cation scavenging ability as described by Baltrusaityte et al (2007) with minor modifications. ABTS + radical cation was produced by mixing 7 mM 2,2'- azino-bis (3- ethylbenzothiozoline-6-sulphonic acid) diammonium salt (ABTS) and 2.45 mM potassium persulfate (K2S2O8), incubated at room temperature in dark. To determine the ABTS radical scavenging activity, 3.9 ml of ABTS+ solution was mixed thoroughly with 0.1 ml of different concentration (10-500 µg/ml) of extracts. The reaction mixture was allowed to stand at room temperature for 6 min and the absorbance was immediately measured at 734 nm. Appropriate blank was prepared and the percentage decrease in absorbance was calculated by the following formula:
Reducing power assay
The reducing power of the extracts determined as per Oyaizu et al. (1986) method. Different concentrations of the extract (10-500 µg/ ml) in 1ml of ethanol were mixed with phosphate buffer (2.5 ml, 0.2M, pH 6.6) and potassium ferrocyanide (2.5 ml, 1%). The mixture was incubated at 50 C for 20 min. To a portion (2.5 ml) of the reaction mixture, trichloroacetic acid (10%) was added, which was then centrifuged at 3000 rpm for 10 minute upper layer of the solution (2.5 ml) was mixed with distilled water (2.5 ml) and ferric chloride (0.5ml, 0.1%) and the absorbance was measured at 700 nm and compared with reference standard ascorbic acid. Increase in absorbance of the reaction mixture indicates reducing power of the sample extracts.
Determination of antimicrobial activity
Test microbial cultures Test bacterial cultures such as Escherichia coli (E.coli), Staphylococcus aureus (S. aureus), and Proteus mirabilis (Pr. mirabilis) were obtained from Post Graduate and research department of Microbiology, M.G.R College, Hosur. Test organisms were sub cultured periodically and maintained on their respective growth media for further study. temperature in dark. To determine the ABTS radical scavenging activity, 3.9 ml of ABTS+ solution was mixed thoroughly with 0.1 ml of different concentration (10-500 µg/ml) of extracts. The reaction mixture was allowed to stand at room temperature for 6 min and the absorbance was immediately measured at 734 nm. Appropriate blank was prepared and the percentage decrease in absorbance was calculated by the following formula:
Screening of antimicrobial activity
The modified (Collins et al., 1995) agar-well diffusion method was employed to determine the antimicrobial activities of all the leaf extracts against three bacterial strains E. coli, Pr. mirabilis, and S. aureus. The bacterial cultures were inoculated into Muller Hinton agar and incubated at 37 ?C. Approximately, 10ml of sterile Muller Hinton agar was poured in to sterile culture plates and allowed to set wells of about 8 mm in diameter were punched on the plates. About 25-500 μg/ml of the extracts were dispensed in to the wells and the plates were incubated at 37 ?C and observed after 24 h.
Statistical analysis
Results are expressed as the mean ± S.D. of three independent experiments (n=3). Student’s t-test was used for statistical analysis; P values > 0.05 were considered to be significant. IC50 was calculated by linear regression analysis using Graph pad prism statistical software.
RESULTS AND DISCUSSION
Phytochemical screening
Presence of bioactive constituents such as phenols, terpenoids, tannins, flavonoids, and saponins in the crude extracts of plant origin contribute to the antimicrobial, antifungal and DPPH radical scavenging activity Free radicals have been a subject of significant interest among scientists in the past decade and their possible role in human diseases has gained importance nowadays (Maxwell, 1995; Jovanovic and Simic, 2000). Antioxidants neutralize free radicals that are defined as atoms or groups of atoms having an unpaired electron (Finkel and Holbrook, 2000). These also include related reactive oxygen species (ROS) that leads to free radical generation, causes the cascading chain reaction in biological system. Antioxidants present in various dietary supplements offered their beneficial effects by neutralizing these ROS during various disease conditions. DPPH radical is widely used as a model to investigate the scavenging potential of several natural compounds such as phenolics or crude extract of plants (Veerapur et al., 2009). In the present study, the ethanolic extracts of Aegle marmelos, Ocimum sanctum, Alternanthera sessilis, Eclipta alba, and Acalypha indica exhibited marked DPPH radical scavenging activity significantly. Lower absorbance of the reaction mixture indicates higher the free radical scavenging activity. Fig. 1 shows that % inhibition decreases the concentration of DPPH radical due to scavenging ability of standard ascorbic acid, as a reference compound and that of the ethanolic extracts. The scavenging effect of AM, OS, AS, EA, and AI and standard ascorbic acid on the DPPH radical decreased in the order: ascorbic acid > AM > AI > OS > EA >AS. The IC50 values for these compounds were found to be 92 μg/ml, 98 μg/ml, 154 μg/ml, 178 μg/ml, 324 μg/ml and 522 μg/ml respectively (Table 3). The results also show that the ethanolic extract of AM possesses significantly higher DPPH scavenging activity than other extracts and were most potent among the five extracts.
ABTS radical scavenging activity
The ABTS assay is based on the inhibition of the radical cation ABTS+ , which has a characteristic long wavelength absorption spectrum (SanchezMoreno, 2002). The ABTS chemistry involves direct generation of ABTS radical mono cation with no involvement of any intermediary radical, it is a decolorization assay, thus the radical cation is formed prior to addition of antioxidant test system rather than the generation of radical taking place continually in the presence of antioxidant. This method is used for the screening of antioxidant activity of herbal preparations, is applicable to both lipophilic and hydrophilic antioxidants (Long et al., 2000). In this study, ABTS radical was effectively scavenged by the ethanloic extract of AM, followed by AI, OS, EA, and AS in a concentration dependent manner but the scavenging effect was lesser than that of the reference compound ascorbic acid (Fig.2). IC50 values were 102 μg/ ml, 110 μg/ ml, 252 μg/ ml, 288 μg/ ml, and 364 μg/ ml for AM, AI, OS, EA, and AS respectively. Similarly IC50 for standard was 96 μg/ ml (Table 4).
Reductive ability
The reducing capacity of a compound may serve as a significant indicator of its potential antioxidant activity (Blazovics et al, 2003). Reducing power is to the measure of the reductive ability of antioxidant and it is evaluated by the transformation of Fe3+ to Fe2+ in the presence of sample extracts (Gulcin et al., 2003).
In this study, the reducing capacities of the extracts were also determined. Results of the reducing power of standard antioxidant ascorbic acid and the ethanolic extracts of AM, OS, AS, EA and AI are shown in Fig. 3. The data show an increase in the reducing power of the extracts with increase in dosage. However, the ethanolic extract of OS presents better activity at a concentration of 500 µg/ml followed by EA, AS, AM, and AI (Table 5).
Antibacterial activity
Plant based antimicrobial compounds have enormous therapeutical potential as they can serve the purpose without any side effects that are often associated with synthetic antimicrobials. The active ingredients of the plant parts are better extracted with alcohol than other solvents. The alcohol extracts contain alkaloids, coumarins and tannins (Okemo, 1996). Coumarins and tannins have antibacterial and antihelminthic properties (Hedberg et al., 1983). Eloff (1998) and Cowan (1999) found that alcohol was more efficient than acetone in extracting phytochemicals from plant materials. In the present work antibacterial effect of leaf extracts from five plants were studied on bacterial cultures (two gram negative bacteria, Proteus mirabilis and Escherichia coli and one gram positive bacterium Staphylococcus aureus). Results of this study revealed that the ethanolic extracts exhibited better antibacterial activity towards all bacterial isolates tested. There was a significant variation in the antibacterial activities of the leaf extracts. The ethanolic extract of AM exhibited highest antibacterial activity followed by OS, AS, EA and AI with diameter of inhibition zone values between 5 and 26 mm. Maximum inhibitory effect was recorded for E. coli 26 mm by AM; followed by Pr. mirabilis 25 mm by OS; for S. aureus, 24 mm by AS (Table 6 and Figures 4, 5, 6 and 7). Tannins were found to be excellent antibacterial compounds (Cowan, 1999). They have diverse effects on biological systems because they are potential metal ion chelators, protein precipitating agents and biological antioxidants (Hagerman, 2002). A number of mechanisms have been proposed to explain the tannin’s antimicrobial activity which includes extracellular microbial enzymes and proteins, deprivation of iron as substances for microbial growth or direct action towards its membranes (Scalbert, 1991). Condensed tannins have been determined to bind cell walls of luminal bacteria, preventing growth and protease activity (Jones et al., 1994). From the results of this investigation, it is therefore postulated that tannins present in the crude extracts were responsible for the antibacterial activity.
CONCLUSION
From the results of this study it could be concluded that all the five medicinal plants contain bioactive principles and found to have a strong antioxidant and antibacterial activities specifically in the ethanolic extract of leaves. Results of our findings further confirm the use of these herbs as traditional medicine and may be used as effective and potential sources of novel antioxidant and antimicrobial drugs
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Fig. 2. Scavenging activity (%) on ABTS radicals of the extracts. Each value is expressed as mean ± standard deviation (n = 3). Am- Aegle marmelos, Os- Ocimum sanctum, As- Alternanthera sessilis, Ea- Eclipta alba, and AiAcalypha indica; and ASC- Ascorbic acid
Fig. 3. Reducing power of the extracts (higher absorbance indicates higher reducing power). Each value is expressed as mean ± standard deviation (n = 3). Am- Aegle marmelos, Os- Ocimum sanctum, As- Alternanthera sessilis, Ea- Eclipta alba, and AiAcalypha indica; and ASC- Ascorbic acid
Fig.4. Antibacterial activities of the extracts against E. coli (agar-well diffusion method). Am- Aegle marmelos, Os- Ocimum sanctum, As- Alternanthera sessilis, Ea- Eclipta alba, and Ai- Acalypha indica
Fig.5. Antibacterial activities of the extracts against S. aureus (agar-well diffusion method). Am- Aegle marmelos, Os- Ocimum sanctum, As- Alternanthera sessilis, Ea- Eclipta alba, and Ai- Acalypha indica
Fig.6. Antibacterial activities of the extracts against Pr. mirabilis (agar-well diffusion method). AmAegle marmelos, Os- Ocimum sanctum, As- Alternanthera sessilis, Ea- Eclipta alba, and Ai- Acalypha indica.
Fig.7. Antibacterial activities of the extracts (agar-well diffusion method). 7 A- Aegle marmelos, S.aureus; 7 B- Aegle marmelos Pr. mirabilis; 7 C- Aegle marmelos, E. coli; 7 D- Ocimum sanctum, S.aureus; 7 E- Ocimum sanctum, Pr. mirabilis; 7 F- Ocimum sanctum, E. coli; 7 G- Alternanthera sessilis, S.aureus; 7 H- Alternanthera sessilis, Pr. mirabilis; 7 I- Alternanthera sessilis, E. coli; 7 JEclipta alba, S.aureus; 7 K- Eclipta alba, Pr. mirabilis; 7 L- Eclipta alba, E. coli; 7 M- Acalypha indica, S.aureus; and 7 N- Acalypha indica, Pr. mirabilis;7 O- Acalypha indica, E. coli.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524152EnglishN2013January26General SciencesMEDICINAL IMPORTANCE OF GENUS INULA- A REVIEW
English2026Samar AminEnglish Zahoor A KalooEnglish Seema SinghEnglish Tabinda AltafEnglishGenus Inula is important medicinally as it has anticancerous, antibacterial, hepatoprotective, cytotoxic and anti-inflammatory properties. The species growing in East Asia are widely used by the local people for varied medicinal properties which have prompted many workers to study the phytochemistry of these species which has ultimately resulted in the extraction of a number of novel bioactive molecules. This emphasizes on the need of extensive study for revealing the medicinal importance of the other species of Inula.
EnglishAlkaloids, Bioactive molecules, Himalaya, Medicinal plant, Sesquiterpenes.INTRODUCTION
In Tunisia, anthocyanins are mainly manufactured from grape marc. Their extraction period is limited to that of the date of harvest which lasts from 15 to 21 days according to years'. The search for other products containing these compounds can be a significant objective. We were initially interested in vine leaves (7). The results showed that certain types contain a foliar anthocyanin compounds with high levels. So their leaves could represent a promising source. In addition, and according to type of vines, the dates of harvests of the raw material, marc and leaves, are not the same ones, which allows their use. Anthocyanin extraction from the leaves would be promising. However, the search for a biotechnological process or a mechanism producing these secondary metabolites is a significant objective. We developed a technique for anthocyanin production in grape leaves (Vitis vinifera L.) cuttings (8). But, this experimental technique presents disadvantages: If we don’t harvest the leaves and the stems induced at the convenient period, yellowing and disturbances of the leaves because of a calcium disorder may occur. Calcium disorder is reviewed (18). Certain plants express this disorder: the tip-burn development in lettuce leaves (1), the bitter-pit in apples (5, 17), the blossom-end rot in pepper fruit, the apex rot potato (4) and the apex necrosis of cabbages (14), the black core of celery (19). Calcium is far from being mobile in the phloem (6, 10, 16) and its distribution depends mainly on xylem (10, 11), which can lead to disorders particularly in fabrics supplied with phloem and in fabrics which transpire little (10). According to Palzkill et al., (14, 15), root pressure can promote water and ions absorption during the night, when there is little water loss following the closing of stomata. Calcium deficiencies of the vine are induced by hydroponic culture (3). Thus, it seems that the migration of calcium is a passive phenomenon assured mainly by transpiration and to some extent by root pressure. We report here to induct a calcium deficiency from the pretreatment by total darkness.
Englishhttp://ijcrr.com/abstract.php?article_id=1430http://ijcrr.com/article_html.php?did=1430Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524152EnglishN2013January26General SciencesINDUCTION OF A CALCIUM DEFICIENCY IN CUTTINGS OF GRAPE VINE (Vitis vinifera L.)
English2837Bechir EzziliEnglishRooted cuttings of grape vine, cvs. ‘Black Grenache’, ‘Carignane’ and ‘Alicante Bouschet’, kept at 25 ± 2° C in the dark, I transferred it 30-days after budburst to a greenhouse at 25°C (day), 20°C (night) and 12 hr light. A week after, foliar growth started and normal green pigmentation appeared. 21 days later, the synthesis of anthocyanins appeared in the leaves and stems. After 28 days, calcium content, expressed as the percentage of dry matter in the shoot apex, decreased and symptoms of calcium deficiency appeared. A hypothesis was proposed to explain the mechanism inducing calcium deficiency by the pretreatment to darkness.
EnglishCutting one eye, pretreatment by darkness, calcium deficiency.INTRODUCTION
In Tunisia, anthocyanins are mainly manufactured from grape marc. Their extraction period is limited to that of the date of harvest which lasts from 15 to 21 days according to years'. The search for other products containing these compounds can be a significant objective. We were initially interested in vine leaves (7). The results showed that certain types contain a foliar anthocyanin compounds with high levels. So their leaves could represent a promising source. In addition, and according to type of vines, the dates of harvests of the raw material, marc and leaves, are not the same ones, which allows their use. Anthocyanin extraction from the leaves would be promising. However, the search for a biotechnological process or a mechanism producing these secondary metabolites is a significant objective. We developed a technique for anthocyanin production in grape leaves (Vitis vinifera L.) cuttings (8). But, this experimental technique presents disadvantages: If we don’t harvest the leaves and the stems induced at the convenient period, yellowing and disturbances of the leaves because of a calcium disorder may occur. Calcium disorder is reviewed (18). Certain plants express this disorder: the tip-burn development in lettuce leaves (1), the bitter-pit in apples (5, 17), the blossom-end rot in pepper fruit, the apex rot potato (4) and the apex necrosis of cabbages (14), the black core of celery (19). Calcium is far from being mobile in the phloem (6, 10, 16) and its distribution depends mainly on xylem (10, 11), which can lead to disorders particularly in fabrics supplied with phloem and in fabrics which transpire little (10). According to Palzkill et al., (14, 15), root pressure can promote water and ions absorption during the night, when there is little water loss following the closing of stomata. Calcium deficiencies of the vine are induced by hydroponic culture (3). Thus, it seems that the migration of calcium is a passive phenomenon assured mainly by transpiration and to some extent by root pressure. We report here to induct a calcium deficiency from the pretreatment by total darkness.
MATERIALS AND METHODS
Grape cultivation
The type of vines tested are Black Grenache, Carignane and Alicante Bouschet resulting from selection massale and carried by 99 Richter, planted in 1975 in the area of El Khenguet AOC Sidi Salem delegation of Grombalia, Department of Nabeul, Tunisia, latitude 10°25’; longitude 36° 37 W; rise: 20 m. Vines were planted 2 m within and 3m between the rows, and trained to north African goblet. Fertilization, pest control and other vineyard operations were consistent with accepted commercial vineyard practices. 2000 cuttings of the cultivars (Black Grenache, Carignane and Alicante Bouschet) coming from apical fragment were cut to a length of 20 cm, disbudded so as to retain only the bud of rank 8, then planted in jars of 1 l containing city water whose composition is as presented (table 1). All cuttings were rooted with a preliminary plastering; the bud is covered with absorbent cotton, a plastic ring covers them, a band plasters is applied to the unit. The hardening of the plaster makes it possible for the bud not to strip. Routing the cutting was done then without problem. The removal of plaster then made it possible for the bud to regain its development. The cuttings were maintained at a total darkness under a relative humidity of 60% and a constant temperature of 23°C ? 2 (fig 1). By daily observations, we identified the number of buds that had reached the stage of bursting called D0. The first appearance of root occurred at the end of 35-40 days at this temperature. After appearing three roots, the buds were removed the plaster (Fig. 2). Bud bursting and branch growth in the darkness were done then without any problem (Fig.3). After 30 days, the stripped buds form then stems with highly reduced 5-6 leaves (fig. 4), characterized by the absence of chlorophyll and anthocyanin pigment. The diameter of the seedling increased. We measured it with a slide caliper. Then, we compared the section of the stem to that of the surface. If D was the diameter of the internodes n°3 in mm, the sectional area of the internodes n° 3 would be given by the formula 3.14 D2 / 4. Measures of the seedlings length and leaf area on this date of the evolution were carried out. The seedlings developed thus, exactly old 30 days, were transferred in to the greenhouse thermo regulated to 25°C day, 20°C night, 12 hours light, 12 hours darkness. After a couple of weeks, a foliar growth was noted and a normal green pigmentation appeared (Fig. 6). After 21 days, reddening of the sheets in red vines appeared (fig. 7). After 28 days in the greenhouse, calcium deficiency took place (fig. 8). They were too, of the measures of length, of the diameter of the internode’s n°3 and the leaf area are carried out. In all the cases, the length of the stem was measured. The leaf area was estimated in the following way: the leaves were detached from the seedling and were photocopied. We used the graph paper and operated with an image division, which we weighed. If P1 is the weight of the sheet image on the graph paper and P0, the weight of 100mm 2 , the surface of the sheet was then estimated by the formula 100P1 /P0 in mm 2 . For the analysis of calcium, the extraction was carried out at a stage of a 28-day stay in the greenhouse. Out of 2000 cuttings placed in the darkness, we retained 30 prototypes for each condition, gathered in a batch. The internodes of the apical and basal part were separated from the leaves which constituted 4 parts different: ISWA= Internodes subjacent with the apex, IB = Internodes of the base. SLA = subjacent leaves of the apex, LB = leaves of the base. The analyses were carried out on each part and we operated five repetitions
Proportioning of calcium
Calcium is proportioned on the product of a nitric extraction at a rate of 25 ml of nitric acid with 0,5% per 20 dry powder matter. Proportioning is done by atomic absorption in flame air-acetylene using standard photometer of flame Pye UnicamPU 9000 Philips. Certain conditions of use of the apparatus are mentioned (Table 2).
RESULTS
Total response of the seepages test screw a live treatment recommended
The growth of seedlings which were cultivated since the departure in the greenhouse had a normal development and did not show any red pigmentation of breaking of the branches at the final stage of their evolution. The pretreatment "darkness" involves symptoms of calcium deficiency to differing degree according to the vine type. For Black Grenache, 41% of the cuttings were affected; this effect was totally absent in Alicante Bouschet (table 3) and significantly less pronounced in Carignane (10%). The symptoms started with surface beaches which were more or less brownish and sunk into the youngest internodes. At this stage, the summit of small size could be still alive. Thereafter, the necrotic zones extended and the tips reached are desiccated. The apex died. Drying gained an apical part of the stem. We will analyse the various parameters, which are responsible for this phenomenon.
Effect of the total darkness on the characteristics of the growth of seedlings
Total darkness induced an increase in the length growth of the branches of vines tested. The darkness caused as a growth in thickness which was definitely as significant as that obtained under the conditions of the greenhouse for black Grenache and Carignane, but not for Alicante Bouschet. Finally darkness reduced of 8-13 times the leaf area according to vine type, compared to the conditions of greenhouse (table 4). There were significant differences between the fresh matter weight of the seedlings cultivated under darkness and in the greenhouse for Grenache, Carignane and Alicante Bouschet. There was no difference between the fresh matter weight of the seedlings cultivated under darkness and in the greenhouse for the same type of vine. There was a significant difference between the dry matter weight of the growths cultivated in darkness and those in greenhouse for three types of vines (table 5). Darkness reduced significantly dry matter production as because of photosynthesis inhibition under this condition. There was more calcium in the basal part than the apical whatever the treatment was, in the greenhouse or in the darkness for the three types of vines. The darkness involved a reduction in the leaf area, and an increase in calcium content. These caracteristics were more pronounced in Grenache and Carignane than in Alicante Bouschet.
Effect of the pretreatment to darkness on the characteristics of the seedlings
Observation after 21 days in the greenhouse The transfer of the cuttings from darkness to the white light has not assigned to then the growth in their shoots length when comparing percentages of the increase between 30 and 51 days compared to the shoots of the cuttings cultivated directly in the greenhouse. Conversely to the length seedlings, the stem section had decreased for all groups. The etiolating shoot acquired different characters and when we returned to the greenhouse, it tended to acquire its origin characters. The transfer from the total darkness to the greenhouse for 21 days induced an increase of the leaf area of 1000%, but it did not allow recapturing the leaf area shoot average of cultivated in the greenhouse since the beginning during 51 days (Table 4 and 6). Concerning the anthocyanin compound leaves of vines, five compounds were detected: Delphinidin 3-O glucoside, Cyanidin, Petunidin, Paeonidin and Malvidin. They were presented in the free and combined form by acetic and coumaric acids (8).
Observation after 28 days in greenhouse
We found the same conclusions concerning the vegetative growth as those done for 21 days in the greenhouse. The principal element was the appearance of calcium deficiency symptoms,with the ultimate ones implying a cellular disintegration membrane of the apical part of the branch what disaggregates intercellular cement by dissociating the tissue structures. In the greenhouse, the growth was normal and there was no synthesis of anthocyanin compounds. There was no significant difference neither of the fresh matter weight nor the dry matter weight between the growths maintained in darkness and those in the greenhouse. There was a modification in the calcium contents particularly in the zone of the apex which decreased by 4 times for black Grenache and by 3 times for Carignane. For Alicante Bouschet, the calcium content was not significantly affected (table7). In the darkness, the dry matter weight is 12% for Grenache and Carignane and 14 % for Alicante Bouschet (table 5). When the growths condition was changed to the greenhouse, the dry matter weight became 13% for Grenache, 14% for Carignane and 15 % for Alicante Bouschet (table 7). There was not variation in the change of the matter fresh weight between the growths exposed directly in the greenhouse and those pretreated by the total darkness. The transfer of the batch from total darkness to the greenhouse had not affected the calcium contents of the basal part of the growth (table 7). In our program two periods were followed: the first was characterized by total darkness during 30 days (phase I) and the second by the transfer in to the greenhouse during 28 days (phase II). In phase I, the stomata closing and the reduced surface of the leaves suggested that water loss by transpiration was weak and the root pressure was dominant. In phase II was characterized by the transfer of the batch from total darkness to the greenhouse and mainly by a resumption of the leaf growth, the transpiration would over ridded it this time on the root pressure and the calcium deficiency was observed. In addition, under temperature conditions, moisture and stationary photoperiod, different calcium absorption happens in the vines stems according to vine type. For black Grenache the calcium contents expressed as the percentage of the dry matter are a quarter, for a one third for Carignane when there was appearance of the necrosis apical symptoms. On the other hand, differences in calcium contents are not significant between treated and witnesses; whereas growth in width stems was practically the same in treated as in the greenhouse, although the foliar growth in the treated seedlings was reduced in the same way as that of two other vine types.
DISCUSSION AND CONCLUSION
The calcium transport for the plants was studied (9, 12, 13, 20). We retain the following data: - Water penetrates through the hair absorbants, gets to the vessels by the bark and the central cylinder: It follows the way of the apoplasm, the symplasm and transcellular transport. - The migration of calcium at long distance is assured passive fact a mainly by transpirant leaves. The root pressure is a way additional or a replacement of transpirant leaves. It determines an ascending transport. - The crude sap distribuates calcium to the various parts of the plant. The calcium content in the elaborate sap is weak. Calcium is not mobile, it is not distributed the oldest leaves towards young. - The apex is supplied with calcium by migration on sites of exchanges. Mitosis and the growth of cells generate new sites of fixation at the level of the plasmalemn and average plate that calcium will occupy by cationic reaction of exchange while following the apoplasmic way. On the basis of these data, we propose an explanation of the manifestation of the calcium deficiency. The pretreatment of the seedlings in total darkness induced etiolation responsible for three vine types, a lengthening of the stem, an abnormal thickness growth and a considerable reduction of the leaf area as well as a blocking of the anthocyanins synthesis. These conditions are due to phototropism and far UV (2). The ascending transport of calcium is done mainly by the root pressure. This means of transport is thus able to feed the growth equipped with their leaves for their calcium apex. It is then the means of transport at long distance from this element under this condition. However it is generally allotted a palliative or complementary function to transpiration (12, 13). In the greenhouse, the growth is normal and there is no synthesis of anthocyanin compounds, the transport of calcium is done by transpiration for the diurnal period and probably by the root pressure at the night. For the vine, the root pressure is effective only if the transpiration feeds it. During the night, It contributes to the continuation of the routing of the calcium imported beforehand in the branches by the transpirant leaves for the diurnal period. Radicular flow would be a temporary vehicle relay of calcium requiring a regular restocking. The passage from total darkness to the greenhouse is followed by a resumption of the seedlings (leaf biomass), a reduction of the stem section and an induction of the biosynthesis of anthocyanins. The physiological state is regained by the conditions of the greenhouse. When the seedlings undergo a preprocessing the darkness followed by that of the greenhouse, the root pressure initially generates an ascending transport of calcium and ensures calcic food for the whole seedlings. During the first days, after the transfer into the greenhouse, the apex is probably supplied with calcium by the root pressure. As the leaf area of the base seedlings increases, the top of the growth is insufficiently fed. The flow of calcium is directed preferentially towards the base, and the symptoms of deficiency appear at the top. As soon as the transpiration of the basal sheets becomes intense, there are deficiency on the apex and appearance of the symptoms of calcium disorder. The migration of water leaves of the base have a relatively large leaf area, the transpiration takes over. The diversion of the flow of calcium towards the mature leaves is probably at the origin of the symptoms of calcium deficiency, which appear on the level of the apical part of the cutting.
Englishhttp://ijcrr.com/abstract.php?article_id=1431http://ijcrr.com/article_html.php?did=14311. Barta, D. J., Tibbits, T. W. (2000). Calcium localization and Tipp burn development in lettuce leaves during early enlargement. J. Am. Soc. Hort. Sci. 125: 294-298.
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Legende of figures
Procedure for the induction of a calcic deficiency at the laboratory
1 Bud is plastered in order to induce roots.
2 When there are at least 3 roots the bud is removed the plaster.
3 bud bursting in darkness
4 Stage six very reduced sheets stage 30 days in darkness
5 Stage 30 days in darkness and in greenhouse. On the left, shoots in total darkness can have 7, 8, 9, 12 very reduced a pale yellow sheets. On the right, cuttings are cultivated in greenhouse give normal axes with spread out and rather large sheets. To note here the difference of lengthening of the branches and growth of the appreciable sheets.
6 Cutting transferred from the darkness to the greenhouse during 15 days. Note here the beginning of colouring of the stems.
7 Cutting transferred from the darkness to the greenhouse during 22 days. To note Curve of the stem of approximately 45°C and sunk red colouring of the carrying branch.
8 Cutting transferred from the darkness to the greenhouse during 30 days. To note the curve of an angle equal to 135°C and beginning of the drying of the apex which starts approximately at a point located at the third of the branch.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524152EnglishN2013January26General SciencesEVALUATION OF INTERLEUKIN-1 IN PATIENTS WITH ORAL SQUAMOUS CELL CARCINOMA AS A MARKER OF PERIODONTITIS
English3841Uma SudhakarEnglish Akila SivaranjaniEnglish Manoj Chand DayanEnglishNew insight regarding the etiology as well as the strategies for prevention of oral cancer is needed. This study was carried out in the Department of Periodontics Thai moogambigai dental college, Chennai and Department of Oncology Apollo Research institute Chennai. Study reveals that there was a significant increase in the level of IL-1 in patients with carcinoma and chronic periodontits.
EnglishINTRODUCTION
The given statistics of oral cancer incidence and survival have remained essentially unchanged over the past three decades despite the accessibility of the oral cavity to direct examination, promotion effects against known risk factors of oral cancer, and advances in the treatment and diagnosis arguing forcibly for new approaches [1] . New insight regarding the etiology as well as the strategies for prevention is needed. Considerable evidence indicates that chronic infections and persistent inflammation are associated with increased cancer risk2 . Periodontitis is a chronic oral infections thought to be caused by gram negative anaerobic bacteria in the dental biofilm 3 .Recent evidence also suggests a significant role for viruses in the initiation and progression of periodontitis .It leads to irreversible destruction of tissue supporting teeth, clinically detectable as periodontal pockets and alveolar bone loss. Periodontitis results in a continuous release of bacterial and inflammatory markers into the saliva and to a lower degree into the blood 4 .The mediators travel to distant sites and adversely affect systemic health. Periodontitis, characterized by epithelial proliferation and migration, results in chronic release of inflammatory cytokines, chemokines, prostaglandins, growth factors and enzymes all of which are closely associated with carcinogenesis5 . Cytokines produced locally have an influence on the development of a particular immune response 6 . Major advances have been made in the field of cytokines regulation of t cell function and so called Type -1 and Type-2 cytokines may play a predominant roles in determining the outcome of the infection7 .IL-1, is a key mediator of chronic inflammatory disease with the potential to initiate tissue destruction and bone loss in periodontal disease 8 . Studies have shown that patients with oral cancer have elevated levels of inflammatory cytokines in their saliva.(Brailo 2011) IL-1 is also used as a marker for early diagnosis of oral cancer using salivary diagnostics methods (Y.Shing 2011).Number of studies suggests a synergy between chronic periodontitis and squamous cell carcinoma independent of smoking status age, race and ethinicity which generates a hypothesis about a possible relationship between periodontal disease and oral neoplasms 9 . In the present study the level of IL-1 in patients with periodontitis and oral cancer was estimated. The aim of this study was to assess the level of IL-1 in patients with oral cancer as a marker of periodontitis using saliva as a diagnostic tool.
MATERIALS AND METHODS
Ethical Considerations: Approval from the ethical committee has been obtained and informed concern was taken from the patient. . Patient care throughout the study was conducted in accordance with the principles of the Helsinki Declaration of 1975, as revised in 2000.
Patients: The study population consisted of patients seen in the Department of Periodontics Thai moogambigai dental college, Chennai and Department of Oncology Apollo Research institute Chennai. The subjects were grouped under four major categories like chronic periodontits, chronic periodontitis with oral squamous cell carcinoma and squamous cell carcinoma alone and the control. Each group consisted of 10 subjects each. Unstimulated whole saliva was collected from each subject. Subjects were asked to rinse their mouth with normal water and then were asked to expectorate whole saliva in the sterile tube. IL-1 in saliva was measured by enzyme linked immunosorbent assay [Human Dental ELISA kit KOREA]. This IL-1β enzyme linked immunosorbent assay (ELISA) applies a technique called quantitative sandwich immunoassay. The microtiter plate provided in this kit has been pre-coated with a monoclonal antibody specific to IL-1β. Standards or samples are then added to the appropriate microtiter plate wells and incubated. After washing to remove unbound IL-1β and other components of the sample, biotin-conjugated polyclonal antibody specific to IL-1β is added and incubated. Laboratory technicians determined the concentrations of salivary biomarkers IL-1.The resulting yellow colour was then read on an ELISA reader and a standard curve was generated to calculate the results.
STATISTICAL ANALYSIS
Chi-square test was used to assess the P-value.
DISCUSSION
Periodontitis is a chronic oral infection caused by inflammatory reactions to gram negative anaerobic bacteria 10 which results in continuous release of toxins and inflammatory markers in the blood stream and saliva. In the present study, IL-1 was significantly more in patients with cancer and periodontitis than patients with only cancer. When compared with the normal subjects IL-1 value was significantly more in subjects with carcinoma (0.016).This is to our knowledge is one of the first study to estimate the level of IL-1 in both oral cancer and chronic periodontitis. Recent evidence suggests a significant role for viruses in the initiation and progression of periodontitis. More interestingly ,studies suggests that periodontal pockets acts as a reservoir for Human papilloma Virus (HPV), 8 cytomegalovirus and Epstein bar virus which are the suspected agents associated with oral cancer. The question of how infection and inflammation can influence carcinogenesis has interested scientists for the past one and half centuries but only now have come up with the certain principles and currently the complexities of this association are emerging. Chronic periodontitis can play a direct or indirect role in carcinogenesis11: 1. Direct effect of micro organism: Micro organisms and their products such as endotoxins, metabolic by products and enzymes [collagenase proteases etc] are toxic to surrounding cells and may directly induce mutations in tumor suppressor genes or alter the signaling path ways that affect the cell proliferation. 2. Indirect effect through inflammation-chronic infection may stimulate the formation of epithelialized tumors through an indirect mechanisms involving activation of surrounding inflammatory cells. Micro organisms activate, [A] The host cells like macrophages, monocytes, lymphocytes to generate reactive O2 species (H2O2 +OXY RADICALS) and matrix metalloproteases which can induce DNA damage in epithelial cells [B] Produce cytokines, chemokines, growth factors and other signals that provide an environment for cell survival, proliferation, migration, angiogenesis and inhibition of apoptosis. This environment may help epithelial cells to accumulate mutations and drive these mutant epithelial cells to proliferate, migrate and give them a growth advantage.
CONCLUSION
In the present study there was a significant increase in the level of IL-1 in patients with carcinoma and chronic periodontits. This study present us to our knowledge the first evidence of association between level of salivary biomarker interleukin 1 in subjects with periodontitis and in oral squamous cell carcinoma. The present study had a smaller sample size, the association needs to be compared by larger studies with a more comprehensive assessment. A specific association between chronic periodontitis and oral cancer is possible .There is a growing need to and explore this possibility, which will have a potential impact on understanding the etiology of oral cancer as well as on its prevention and control.
Englishhttp://ijcrr.com/abstract.php?article_id=1432http://ijcrr.com/article_html.php?did=14321. Canto MT, Devesa SS.Oral cavity and pharynx cancer incidence rates in United States 1975-1998.Oral oncology 2002; 38: 610-617.
2. Karin M, Lawrence T, Nizet V, Innate immunity gone away:linking microbial infection to chronic inflammation and cancer.Cell.2006;124:823-835.
3. Mine Tezal, Mayreen A, Sullivan, Andrew Hyland et al, Chronic periodontitis and the head and neck squamous cell carcinoma, Cancer epidemiology biomarkers prevention 2009;18(9) September 2009.
4. Champagne CME,Buchanan W,Reddy MS,Pressier JS,Beck JD,Offenbaxher S.Potential for gingival crevice fluid measures as predictors of risk of periodontal disease.Periodontal 2000,2003;31:167-80.
5. Loesche WJ, Grossman NS,Periodontal diseases as a specific,albeit chronic infection :diagnosis and treatment .Clinical microbiology Rev 2001;14:727-752.
6. E.Gemmell and GJ.Seymour, cytokine profiles of extracted from humans with periodontal diseases; J Dental Research 77(1):16-26,January 1998.
7. Cytokine profiles of cells extracted from humans with periodontal diseases,E.Gemmel and G.J.Seymour,J Dent Res 77(1):16-26.
8. Horimia M,Willberg J,Ruokonen H,Syrjanen S,Marginal periodontium as a potential reservoir of human papilloma virus in oral mucosa.J Periodontal.2005;76(3):358-363.
9. SaygunI,Kubar A,Ozdemir A,et al Periodontitis lesions are source of cytomegalovirus and Epstein Barr Virus .J.Periodontal Res.2005;40:187-191.
10. Tezal M, Grossi SG, Genco RJ, Is Periodontitis associated with oral neoplasms?J Periodontology 2005:76:406- 10.
11. Chronic periodontitis and risk of tongue cancer Mine Tezal, DDS, Phd ;MaureenA.Sullaivan, DDS; Mary E.et al; Arch Otolaryngol Head Neck Surg. 2007; 133: 450-454.
STATISTICAL ANALYSIS:
Chi-square test was used to assess the P-value.
RESULTS
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524152EnglishN-0001November30HealthcareUNUSUAL FINDING OF CYSTIC CHANGES IN HASHIMOTO'S THYROIDITIS: A REPORT
English4244Ashwini B.R.English Sunita VernekarEnglish Rajeshwari BhuttannavarEnglishHashimoto’s thyroiditis(HT) is a chronic autoimmune thyroiditis affecting women more commonly. It is characterized by lymphoplasmacytic infiltration of thyroid follicular cells, hurthle cells resulting in atrophy of the follicular cells and fibrosis. Cystic change is an unusual finding in Hashimoto’s thyroiditis. A 35 year old female presented as nodular goiter clinically with ultrasound showing multiple cystic areas. Histopathological examination of the specimen after thyroidectomy showed features of Hashimoto’s thyroiditis with cystic areas. We report a rare case of Hashimoto’s thyroiditis with cystic changes in for the first time to the best of our knowledge. A more detailed study in this regard is warranted to understand the pathogenesis of cystic changes in HT.
EnglishHashimoto’s thyroiditis, cystic changesINTRODUCTION
Hashimoto’s thyroiditis (HT) is an autoimmune disorder, characterized histologically by lymphoplasmacytic infiltration of thyroid follicular cells, hurthle cells resulting in fibrosis and atrophy of the cells. Cystic changes are an unusual finding in HT. We report the first case of HT with cystic changes.
CASE REPORT
A 35 year old female patient presented to our hospital with history of swelling in front of the neck from 2 years. Swelling was gradually increasing in size. There were no symptoms of hypothyroidism or hyperthyroidism in the patient. On examination there was a firm swelling with nodular surface measuring 9x6 cms. Patients pulse rate was 80/min, and BP was 120/82 mm of Hg. A clinical diagnosis of nodular goiter was made. Ultrasound showed enlargement of both lobes with multiple cystic areas with thick internal contents. Fine needle aspiration cytology of thyroid showed follicular cells in clusters, Hurthle cells with scant lymphocytic infiltration in the background of thin colloid. Diagnosis of nodular goiter was made. Thyroid function tests showed T3 162.8ngm/dl, T4 8.7µgms/dl and TSH 2.4 µIU/dl. Subtotal thyroidectomy was done. Post operatively the thyroid specimen was sent to the department of pathology. The specimen consisted of both lobes of thyroid with isthmus and was nodular. Cut section was gray white with lobular and cystic areas as in Figure 1. Histopathology showed dense lymphocytic infiltration with destruction of follicular cells. Hurthle cells, cystic areas with colloid and cyst macrophages were also seen. The cystic spaces did not have any lining epithelium as in figure 2. Immunohistochemistry showed polymorphous population of lymphocytes surrounding the follicular cells.
Figure 2: [A]- Thyroid follicles with dense lymphocytic infiltration and germinal center formation (4x). [B]- Lymphoplasmacytic infiltration with destruction of the follicles (10x). [C]- Hurthle cells with atrophic follicles with cystic space in the left upper corner (40x). [D]- Cystic spaces showing cyst macrophages and colloid with no lining epithelium (40x). Diagnosis of Hashimoto’s thyroiditis with cystic changes was made. Post-operative evaluation of the patient showed seropositivity for antithyroglobulin antibodies.
DISCUSSION
Lymphoplasmacytic infiltration of follicular cells causes atrophy of the cells with fibrosis and sclerosis. Autoimmune B and T lymphocytes along with reactive intermediates induce apoptosis and also damage the thyrocyte cell membrane causing thyrocyte necrosis1 . Cystic changes occurs in nodular goiter is due to vascular compromise, ischemia and necrosis. Cystic change can be seen in HT associated with secondary pathology like papillary carcinoma and malignant lymphoma. Matsuzuka et al reported a case of HT who developed small cyst like pattern on serial ultrasound2 . Histopathology showed features of malignant lymphoma with HT. Mitteldoff et al reported a case, seropositive for Human immunodeficiency virus (HIV) showing bilateral complex cysts with high titers of antimicrosomal antibodies. Cysts showed heterogenous
lymphocytic population and occasional groups of immature squamous cells with cytological features of autoimmune thyroiditis3 . True cysts lined by squamous epithelium, bordered by a row of lymphoid follicles in thyroid is been reported by Louis et al4 . Our case was sero-negative for HIV and the cystic spaces had no lining epithelium.
CONCLUSION
Cystic changes in HT are of rare occurrence. The lymphocytic infiltration in HT induces fibrosis rather than cystic degeneration. A case with cystic changes in HT being reported for the first time to the best of our knowledge.
RECOMMENDATIONS
A more detailed study in this regard is warranted to understand the pathogenesis of cystic change in HT.
ACKNOWLEDGEMENT
The authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors/editors/publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed. DECLARATION ON CONFLICT OF INTEREST: Nil
Englishhttp://ijcrr.com/abstract.php?article_id=1433http://ijcrr.com/article_html.php?did=14331. Dimitry A Chistiakov. Immunogenetics of Hashimoto’s thyroiditis. Journal of Autoimmune Diseases 2005;2:1
2. FurmioMatzuzuka, Nobuyuki Amino, Kanji Kuma, Akira Miyauchi. Serial changes in thyroid ultrasonogram in a patient with Hashomoto’s thyroiditis who developed malignant lymphoma. Thyroid 2005;15(7):742- 43
3. Cristina A.T.S Mitteldorf, Antonio Carlos de OliveriaMisiara, Iara Emiko de Carvalho. Multicystic Autoimmune thyroiditis-like disease associated with HIV infection a case report. Acta cytol 1999;43:862-66
4. Multiple Branchial cleft like cysts in Hashimoto’s thyroiditis. American journal of surgi Pathol 1989;13(1)
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524152EnglishN2013January26HealthcareFAMILY AND CHILD CORRELATES OF MOTOR DEVELOPMENT OF TODDLERS IN INDIA
English4557Balasubramanian SundaramEnglish Y. S. SiddegowdaEnglishPurpose: To analyze the family- related and child- related factors that are related to the motor development of toddlers and to determine the most significant factors among them.
Methods: Fifty urban and fifty rural families with children aged one to three years old were recruited through multi-stage cluster random sampling from Bangalore urban and Bangalore rural districts respectively. Suitable and valid measurement tools were used to assess the family-related and child- related factors. The gross motor and fine motor development of toddlers were measured by using Psychosocial Development Screening Test. A multiple logistic regression analysis was done to identify the factors influencing the motor development of toddlers.
Results and Interpretation: The toddlers brought up in a non – stimulating home environment had 4.25 times and 4.75 times delayed gross motor and fine motor development respectively, than those brought up in a stimulating home environment. The toddlers brought up by authoritative parents had 0.54 times normal gross motor development compared to those brought up by authoritarian and permissive parents.
Conclusion: A stimulating home environment and authoritative parenting style are significant correlates of gross motor development of toddlers, whereas only the stimulating home environment is significantly correlated with fine motor development of toddlers in India.
EnglishGross Motor Development, Fine Motor Development, Home EnvironmentINTRODUCTION
During toddlerhood, though remarkable advances occur in language and cognitive development the progress is obvious in all the developmental domains including motor development.1 Motor development refers to changes in motor behavior that are related to age and assists the children to control their body movements. It emerges from infants’ initial impulsive waving and kicking movements to the adaptive control of reaching, locomotion, and complex sport skills.2 The term ‘motor behavior’ describes all movements of the body and can be classified into gross motor and fine motor behavior. When performing gross motor skills such as standing, walking, jumping, running, jogging, and throwing a ball children use large muscles of their legs and arms or the entire body, whereas during fine motor behaviors such as the eye movements to follow objects and movements of fingers to grasp and manipulate objects, the small muscles of eyes and fingers are involved respectively. 3 Unlike newborns, toddlers’ bodies have a more cylindrical shape, and they have a larger ratio of muscle mass to body fat, predominantly in the legs. These changes in weight, size, percentage of body fat, and muscle strength endow with perceptual/motor challenges to toddlers as they practice a variety of motor actions.4 During the toddler years, the gross motor skills develop rapidly. By 18 months, most children walk without assistance and soon, they learn to walk faster with a few falls. Around 2 years old, they walk steadily with an adult-like heel-toe progression. By 36 months, they will develop their balance and can stand on one foot momentarily. Toddlers delight in their new-found skills and often can be seen experimenting with them. As any person who has cared for a toddler can attest, they climb, they jump, and they run. Supervision is essential for preventing injury because toddlers sometimes test their skills beyond their abilities in an attempt to learn and do more.1 Increasing fine motor abilities during toddlerhood result from refinements in reaching, grasping, and manipulating small objects. The average 18- month-old can make a tower of four blocks. Just one year later, with practice and improved control, he or she can stack eight blocks. Most 18-month olds have developed an interest in crayons and, if given the opportunity, will hold the crayon in a fist and scribble spontaneously on paper (or anywhere else). After one and half years, toddler will develop the control and sophistication to pick up a crayon by placing the thumb at the left and fingers at the right of the shaft and make a circle; by age three, the child even may begin to draw a primitive stick figure.1 Family is the first environment with which children interact from birth and is significantly important in providing children with stimulation, support, and nurturance.5 The toddlers select an optimal movement required for a new motor ability after exploring a variety of movement options and this process needs an interaction between multiple elements of toddler, and the environment, and the task.6 Thus the physical condition of the home and provision of toys encourage the toddlers to practice a variety of sensory experiences and to be able to develop gross and fine motor skills.7 Parenting styles are the collection of parents’ behaviors which create an atmosphere of parentchild interactions across situations.8 Baumrind outlined three typologies of parenting styles known as authoritative, authoritarian, and permissive parenting. Authoritative parenting offers a balance between high nurturance and high control, allowing the child room to exercise autonomy. Authoritarian parenting restricts autonomy through high coercive control and low nurturance and support. Permissive parenting is high in nurturance and support while being low in control, allowing an excess of autonomy without engendering responsibility.9,10 Each style has a different influence to each child development areas. The socioeconomic status (SES) of the family and family relationship also influence the children’s development, for those with high economical status and good family relationship had better development than those in low economic status and poor family relationship.6,11 A greater part of the Indian population lives in villages.12 The toddlers get fewer opportunities to develop their full prospective as their mothers lack knowledge regarding scientific child care, stimulatory activities and conducive environment which are essential for hale and hearty development.13 The parents’ educational levels have an important impact on children’s achievement,14 and higher levels of adult education have a positive bearing on both the educational future and the income level of the children in a family.15 Being early in the birth order may be rewarding for child development, because a child that is early in the birth order lives in a smaller family for a longer time and hence may get a larger share of the family resources when young than its younger siblings. The dilution may not be limited to quantity of resources but may also occur for the quality of the investments received by a child.16-19 Even though all the above factors are related to the motor development of toddlers, the decisive factors among them are yet to be identified. Therefore, this study was conducted to determine the most significant factors among the familyrelated (parental literacy status, location of residence, home environment, preferred parenting style, family type, family’s economic status and maternal employment) and child- related factors (number of siblings and order of birth) that are associated with the motor development of toddlers through a suitable regression analysis.
METHODS
In this explanatory cross-sectional study, a multistage cluster random sampling technique was used for data collection. All the taluks of Bangalore urban (Bangalore North, Bangalore South, Bangalore East and Anekal) and Bangalore rural (Nelamangala, Dodballpura, Devanahalli, Hosakote) districts were included for the study. By using computer generated random numbers, three villages were randomly selected from each taluk in Bangalore rural district, and then hundred households were randomly selected from each village. In the similar way three towns were selected from the Bangalore urban district and from each town hundred households were randomly selected. A preliminary survey was conducted during February and March of year 2008 to identify the families with children aged one to three years. Then based on the literacy status of the parents the households were categorized as families with both the parents literates, families with both the parents illiterates and families with one of the parents literate or illiterate. The families with one of the parents literate or illiterate were not included in the study. In Bangalore urban district, 367 families were identified with children aged between one and three years, among them in 207 families both the parents were literates, in 127 families both the parents were illiterates, and in 33 families one of the parents were literate or illiterate, who did not participate in the study. Among 207 families with both the parents literates, 146 met the selection criteria and 98 were willing to participate in the study and from these 98 families 25 families were selected randomly by using computer generated random numbers to form the Urban Literate group. Among 127 families with both the parents illiterates, 99 fulfilled the selection criteria and 82 were willing to participate in the study and from these 82 families 25 families were randomly selected by using computer generated random numbers to form the Urban Illiterate group. In Bangalore rural district, 312 families were identified with children aged between 1 and 3 years, among them in 156 families both the parents were literates, in 133 families both the parents were illiterates, and in 23 families one of the parents were literate or illiterate, who did not participate in the study. Among 156 families with both the parents literates, 130 families met the selection criteria and 108 were willing to participate in the study and from these 108 families 25 families were selected randomly by using computer generated random numbers to form the Rural Literate group. Among 133 families with both the parents illiterates, 110 families fulfilled the selection criteria and 103 were willing to participate in the study and from these 103 families 25 families were randomly selected by using computer generated random numbers to form the Rural Illiterate group. Thus totally four groups were formed.
Participants:
From these four groups, at least one of the parents with their children aged between one and three years old had participated in the study. If there were more than one child in that age group in the same family, one of the children was selected randomly by using lottery method. After being approved by the Institution’s Review Committee, an informed written consent was obtained from all the participants (parents) who were willing to participate in the study after explaining the purpose and procedure of the study. After completing the preliminary assessment, the information regarding parenting style, observation of family environment and screening of the target child’s motor development was done from those families who were ready to devote time (one and half to two hours) during the first visit itself. From the remaining families, an appointment was received based on their convenience to collect the whole data. The phone number was also received during the first visit to remind them about the appointment prior day and to ensure the presence of primary caretaker during the subsequent visits.
Selection Criteria:
The toddlers from both the genders, born in term with normal birth weight (2.5 to 3.5 kg) and appropriate for gestational age, and having age appropriate anthropometric measurements such as height, weight and head circumference were included in the study and the toddlers with a history of any congenital anomalies, neonatal seizures, perinatal asphyxia, neonatal hypoglycemia, intracranial hemorrhage, neonatal hyperbilirubinaemia (bilirubin > 20mg/dl and untreated), hypothermia, neonatal infections and septicaemia were excluded from the study and if the parents were not sure about the above features or no medical reports were available, the parents were asked whether the child was admitted in the Neonatal Intensive Care Unit (NICU), as admission of a newborn in NICU may be due to any of the above mentioned causes.
Assessment Tools
The literacy status of the parents was assessed by using the UNESCO’s operational definition of literacy.20 To assess the parenting style, Parenting Style Questionnaire [PSQ]21 was used. The illiterate parents answered the questions in PSQ by schedule method. The Infant/Toddler HOME Inventory22 was used to observe the home environment of the toddlers and the gross motor and fine motor development of the toddlers were assessed by using the Psychosocial Development Screening Test [PDST].23-25
DATA ANALYSIS AND RESULTS
The data analysis was performed by using the statistical software SPSS 16 (Inc., Chicago, IL) for windows. Descriptive statistics were calculated for all the basic characteristics like age, gender, height, weight, and head circumference. One way ANOVA and chi-square test were used to determine the homogeneity of the four groups, which revealed that all the four groups were homogenous in terms of age, gender, height, weight, and head circumference at p>0.05 (Table 1). The descriptive analysis for familyrelated factors (home environment, preferred parenting style, family type, economic status, maternal employment), and child- related factors (order of birth, and number of siblings) is displayed in Table 2. Kruskal – Wallis test showed a statistically significant (pEnglishhttp://ijcrr.com/abstract.php?article_id=1434http://ijcrr.com/article_html.php?did=14341. Eve R. Colson, Paul H. Dworkin. Toddler Development. Pediatrics in Review. 1997;18(8):255-259.
2. Adolph KE, Weise I, Marin L. Motor Development. In, Encyclopedia of Cognitive Science. London, Macmillan; 2003.
3. Adolph KE. Learning in the Development of Infant Locomotion. Monographs of the Society for Research in Child Development. 1997;62(3).
4. Adolph KE, Berger SE. Motor Development. In, Damon W, Lerner R (eds). Handbook of Child Psychology, Cognition, Perception, and Language, 6th edition, vol. 2. New York, John Wiley and Sons; 2006.
5. Ross D. Parke, Virginia Otis Locke. Child Psychology, Updated 5th edition. McGrawHill Higher Education; 2003. 6. Zill N. Parental schooling and children’s health. Public Health Rep. 1996;111:34-43.
7. Bronfenbrenner U. Ecology of the family as a context for human development: Research perspectives. Dev Psychol. 1986;22(6):723- 741.
8. Mize J, Pettit GS. Mothers' social coaching, mother-child relationship style, and children's peer competence: Is the medium the message? Child Dev. 1997;68(2): 312-332.
9. Baumrind D. Current Practices of Parental Authority. Developmental Psychology Monograph. 1971;4:1-2.
10. Baumrind D. Child care practices anteceding three patterns of preschool behavior. Genet Psychol Monogr. 1967;75:43-88.
11. Bronfenbrenner U. The Ecology of Human Development: Experiments by Nature and Design. Cambridge, MA, Harvard University Press; 1981:348.
12. Goldy Chopra, Shubhangna Sharma, Shipra Nagar. The Impact of Intervention on Motor and Mental Development of Rural Female Infants in District Kangra of Himachal Pradesh. J Hum Ecol. 2004;15(3):223-225.
13. Vander Z, James W. Human Development. Academic Press, New York; 1977.
14. Davie Ronald, Butler Neville R, Goldstein Harvey. From birth to seven. New York, Humanities press; 1972.
15. DeBruin-Parecki A, Paris S, Siedenburg J. Family literacy: Examining practice and effectiveness. J Adolesc Adult Literacy. 1997;40:596-605.
16. Blake J. Family Size and the Quality of Children. Demography. 1981;18(4):421-442.17. Leibovitz A. Parental Inputs and Children’s Achievement. Journal of Human Resources. 1977;12:247-249.
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19. Becker GS, Lewis HG. On the Interaction between the Quantity and Quality of Children. Journal of Political Economy. 1973;81(2):279-288.
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27. Evans GW. Child Development and the Physical Environment. Annu Rev Psychol. 2006;57(1):423-451.
28. Bradley RH, Caldwell BM, Rock, SL, Barnard K, Gray C, Hammond M, et al. Home environment and cognitive development in the first 3 years of life: A collaborative study involving six sites and three ethnic groups in North America. Dev Psychol.1989;25:217-235.
29. Bober SJ, Humphry R, Carswell HW, Core AJ. Toddlers' persistence in the emerging occupations of functional play and selffeeding. Am J Occup Ther. 2001;55:369-376.
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31. Malik M, Pradhan SK, Prasuna JG. Screening for psychosocial development among infants in an urban slum of Delhi. Ind Pediatr. 2007;74:841-845.
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33. Berger L, Paxson C, Waldfogel J. Income and Child Development. Mimeo, University of Princeton; 2005.
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SD: Standard deviation; Min, Max: Minimum and Maximum. a p values were calculated using ANOVA; b p value was calculated using chi-square test
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524152EnglishN2013January26HealthcareANALYSIS OF Por AND TbpB GENES OF NEISSERIA GONORRHOEAE TO IDENTIFY POTENTIAL MOLECULAR SIGNATURE FOR DETECTING RAPE ACCUSED
English5865Arvind Kumar RajanEnglish Dhairyawant KushwahaEnglish Vijay KumarEnglish Gireesh Babu K.EnglishSexually transmitted infections are a major public health problem. The French laboratories participated on voluntary basis in the RENAGO (Réseau National du Gonocoque) network and sent all of their collected strains to the National Reference Center for Neisseria gonorrhoeae. Gonorrhoea, caused by the gram-negative bacterium Neisseria gonorrhoeae, remains one of the most common sexually transmitted infections (STIs), causing cervicitis, urethritis, ano-rectitis, and conjunctivitis of the newborn. Over the last few years, the number of gonorrhoea cases has increased regularly in many European countries (Fenton, K. A., and C. M. Lowndes. 2004). Since the first report of tetracycline resistance in 1985, gonococci that are resistant to tetracycline have spread globally, coexisting chromosomally and plasmid-mediated resistanc isolates (Starnino, S., A. Neri, and P. Stefanelli. 2008.). At present, there is no effective vaccine against N. gonorrhoeae. The control of gonococcal infections depends on in pursuing of our populations at risk, on public health measures to limit the spread of infection, and on early intervention to treat infected individuals. Any kind of methods have been used for molecular epidemiology studies of N. gonorrhoea. Some of these methods are based on growth requirements for specific nutrients, antibiotic susceptibility, differences in multilocus enzyme electrophoresis, and serological reactivity against surface antigens. Because the above approaches present several limitations, molecular typing methods have been developed with improved discrimination among gonococcal isolates. Of the currently available sequence-based methods, N. gonorrhoeae multiantigen sequence typing (NG-MAST) is one of the most useful because it generates a simple numerical sequence type (ST) based on the combined sequences of two genes (por and tbpB). In addition, an internationally accessible web database allows strain comparison worldwide (Martin, I. M., S. Hoffmann, and C. A. Ison 2006).
EnglishINTRODUCTION
A crime that typically produces physical evidence. Often, only the victim and the perpetrator are present when the crime occurs, so this evidence is critical. Sexual assault includes rape, both heterosexual and homosexual, child rape and abuse, and elder abuse. Sexual assault can also be part of other crimes such as burglary and murder. The key points of evidence collection are at the scene and also at the hospital or other medical facility where the victim is examined. This collection can also occur during autopsy. In either case, sexual assault evidence collected by medical personnel centers on the sexual assault kit, which consists of blood, body fluids (principally semen and saliva), and many other items. Trace evidence can be significant as well since an assault try to edit lends itself to rich transfer of fibers, broken fingernails, and forcibly removed hair, for example are playing an increasingly important role in sexual assault cases.
There are also many advantages to using DNA fingerprinting in sexual assault or rape cases. DNA fingerprinting is accurate at identifying a rapist based on evidence left behind on the victim. Detectives can simply match the DNA of the specimen found at the crime scene/ after the crime time, with the DNA of the alleged suspect determine who is guilty of the crime. DNA samples from the alleged rapist can be collected through a vaginal swab from the victim or on other semen found in the scene or from the clothing. By applying molecular-biology methods, DNA profiling uses repetitive ("repeat") sequences that are highly variable (Accessexcellence.org) called variable number tandem repeats (VNTRs), particularly short tandem repeats (STRs). VNTR loci are very similar between closely related DNA samples, but so variable that unrelated individuals are extremely unlikely to have the same VNTRs. Besides these repeats PCR-RFLP might also be useful for the aforesaid purpose. Sexual assault is a violent crime that affects men, women, and children of all ages. Sexually transmitted diseases (STDs) may be transmitted during sexual assault. In children, isolation of sexually transmitted organism may be the first indication that abuse has occurred. The bacterium Neisseria gonorrhoeae causes gonorrhoea, a disease which is almost exclusively transmitted during sexual intercourse. Currently, isolation and identification of the causative organism remains the gold standard for a definitive diagnosis. Although tests requiring cultures of the bacterium are considered to be best for a definative diagnosis, molecular methods relying on only bacterial DNA are improving in sensitivity and specificity. However, nucleic-acid based techniques are being used more frequently as sensitivity and specificity of the newer tests are improved (Palmer et al., 2003), although none have been licensed for use with specimens from non-genital sites, including the rectum and the pharynx. There is also little validation of molecular methods for diagnosis of gonorrhoea in children and they should be used with caution as the prevalence of infection is likely to be low (Hammerschlag, 2001).These can permit detection and typing of N. gonorrhoeae in situations where the bacterium cannot be cultured. For medico-legal cases there is a need to not only confirm the presence of N. gonorrhoeae, but to prove a link, or the absence of one, between the strains isolated from each individual. DNA markers therefore need be selected so that they accumulate variation sufficiently rapidly to exclude unlinked individuals who happen to suffer from gonorrhoea, while still allowing identification of individuals who are sexual contacts or part of a short transmission chain. A database of suitable DNA markers for N. gonorrhoeae acceptable in a court of law is not yet available. However, researchers have a database from two of the bacterium’s most variable genes containing information on over 4,000 different strains. This is the N. gonorrhoeae multi-antigen sequence typing database (NG-MAST), but since the strains were collected during specific studies, they do not give a complete picture of all the types present within a particular geographical area. However, researchers were recently faced with a request for N. gonorrhoeae confirmation that utilized NGMAST, and provided the first reported typing of gonococcal DNA from clothing for medico-legal reasons. In medico-legal cases, such as sexual abuse of a child or rape, it is necessary not only to confirm the presence of the infecting organism but also to attempt to prove linkage between the isolates from each individual involved. Typing of gonococcal isolates has been used try to edit because it can support or dispute the likelihood of transmission between individuals, and newer molecular methods offer greater discrimination compared to phenotypic methods (Ison, 1998). A genotypic method needs to be based on a target that accumulates genetic variation quickly so individuals that are sexual contacts or part of a short transmission chain should demonstrate an indistinguishable type, while individuals that are unlinked should have different types. N. gonorrhoeae multi-antigen sequence typing (NGMAST) is a sequence-based method examining the diversity in two outer-membrane proteins, Por and TbpB (transferrin binding protein B), allowing the precise characterization and comparison of gonococcal samples, with all analysis performed via a website (http://www.ngmast.net). The method has been shown to identify epidemiologically linked individuals and distinguish between individuals that are not linked (Martin et al., 2004). Ideally, variation in hyper-variable genes, resulting from genetic exchange and recombination during mixed infection, should produce a changing population of molecular types over time. Highly diverse populations have been identified (Choudhury et al., 2006) but persistence of molecular types within a population has also been shown (Ward et al., 2000) and may reflect a lower rate of partner change and hence chance of mixed infection. The Sexually Transmitted Bacteria Reference Laboratory (STBRL) at the Health Protection Agency Centre for Infections uses molecular methods for confirmation of identity and typing when isolates are received from potentially linked sources, to support or dispute the likelihood of transmission of gonorrhoea. This short report describes the first use of molecular methods to confirm the presence of N. gonorrhoeae from adult clothing and provide evidence of possible linkage to an isolate from a child (Martin et al. 2007). Since there are major reports on the presence of molecular candidate markers which can detect or discriminate the rape accused from rape victims while using the sexually transmitted agents, the present study is designed with the following
• Retrieval of Por and TbpB genes sequences of Nesseria gonohorroea strains. Identification of DNA based signature by comparative in-silico analysis of retrieved Por and TbpB genes sequences.
• In silico validation of selected DNA signatures.
MATERIAL AND METHOD
N. gonorrhoeae isolates.
A first group of 67 isolates (group I) was selected from different antibiotic resistance phenotypes and then from different geographic origins, from male and female patients, and finally from different sampling locations (cervix, urethra, urine, and knee fluid), identify possible clusters. A second group of 26 isolates (group II) was selected from rectal samples from men who have sex with men (MSM), without of antibiotic phenotype restriction criteria, in order to identify specific clusters in this high-risk population.
Culture and identification
The isolates were cultured on PVX chocolate agar (bioMérieux, Marcy-l'Étoile, France) supplemented with 1% IsoVitaleX and incubated overnight at 37°C with 5% carbon dioxide. Identification was performed with the API NH system (bioMérieux, Marcy-l'Étoile, France).
Phenotypic analysis
Isolates were tested by routine analysis for antibiotic susceptibility and serotype. Susceptibility to six antibiotics (penicillin, ceftriaxone, tetracycline, ciprofloxacin, spectinomycin, and erythromycin) was measured using the disk diffusion method (bioMérieux, Marcy-l'Étoile, France). β-Lactamase production was detected by the cefinase test (bioMérieux, Marcy-l'Étoile, France). Etests (AB Biodisk, Sweden) were used to determine MICs of penicillin, ceftriaxone, tetracycline, ciprofloxacin, and spectinomycin. Results were interpreted according to the Clinical and Laboratory
Standards Institute (CLSI). Isolates were serotyped with the Phadebact GC serovar test using monoclonal antibodies (Orgentec SAS, Trappes, France).
DNA extraction
Isolates were retrieved from storage at −80°C in glycerol broth, cultured on PVX chocolate agar supplemented with 1% IsoVitaleX, and incubated overnight at 37°C with 5% carbon dioxide. A turbid suspension of the gonococcal subculture was made in phosphate-buffered saline (optical density of ~2.0). The bacteria were pelleted by centrifugation at 2,000 × g for 5 min, washed once, resuspended in phosphate-buffered saline, and boiled for 5 min to lyse the cells. The lysate was centrifuged for 5 min at 2,000 × g, and the supernatant was stored at −20°C until required.
Molecular typing by NG-MAST
Briefly, internal regions of the por and tbpB genes were amplified by PCR from the DNA extracts, and both strands were sequenced using with Big Dye v.1.1 chemistry on an ABI3730XL capillary sequencer (Applied BioSystems). Sequences were aligned, edited, and trimmed to a fixed length from conserved positions as described previously (Martin, I. M., S. Hoffmann, and C. A. Ison. 2006.) using BioNumerics software (Applied Maths, Belgium). Alleles were assigned to each sequence variant of por and tbpB, and the corresponding ST was assigned through the NG-MAST website (http://www.ngmast.net) based on the combination of the alleles of the two loci.
RESULTS
The 67 group I isolates (from a heterosexual population and various geographic and clinical sources) came from India and its surroundings (25 isolates [37%]) and from other regions (42 isolates [63%]). Sixty-one isolates were from males and 6 from women. This low number of isolates from women could be explained by the asymptomatic or paucisymptomatic gonococcal infections observed in women who did not attend an STI clinic. The diagnosis of N. gonorrhoeae infection is more often casual, generally a gynecological checkup carriage in women is characterized by a low number of bacteria, which are particularly difficult to isolate, among the commensal vaginal bacteria. The ages were known for 56 men (mean, 32 years; range, 18 to 57 years) and 5 women (mean, 31 years; range, 18 to 62 years) and unknown for 6 other patients (5 men and 1 woman). Fifty-six isolates were obtained from male urethra, 6 from cervix, 4 from male urine, and 1 from the fluid of a male's knee. The last isolate was included because it was collected from an exceptional location and characterized by the rare antibiotic resistance phenotype 2. The majority of the group II isolates (MSM) came from India and its surrounding area (88%), with an average patient age of 33 years (range, 20 to 54 years). Based on the MICs obtained for penicillin (with or without β-lactamase production), tetracycline, ciprofloxacin, ceftriaxone, and spectinomycin, the 93 isolates could be classified into six phenotypes representing an overview of the diversity of antibiotic resistance phenotypes observed in France. Thirty-nine (42%) isolates had antibiotic susceptibility phenotype 3, characterized by a susceptibility to all tested antibiotics, whereas 31 (33%) isolates had phenotype 4 (with reduced susceptibility to ceftriaxone and high-level resistance to ciprofloxacin). The remaining isolates were divided into the four other susceptibility phenotypes, which was distinguish by their combination of resistance to tetracycline, ciprofloxacin, and ceftriaxone. Based on NG-MAST, the 93 isolates were subdivided into 53 different STs, including previously described STs as well as new STs. Most STs (75%) were only represented by single isolate, whereas the remaining STs were represented by 2 to 16 isolates. The 13 most common STs were ST225 (16 isolates [17.2%]);
ST1479 (9 isolates [9.7%]); ST880 (4 isolates [4.3%]); ST26, ST437, ST975, and ST1986 (3 isolates [3.2%]); and ST2, ST211, ST292, ST359, ST1813, and ST1987 (2 isolates [2.1%]). Among the 67 group I isolates, we could identify 36 different STs, 10 of which included more than one isolate (ST225, ST1479, ST26, ST975, ST437, ST1986, ST2, ST1987, ST211, and ST880), together clustering 61% of the isolates.Regarding the 26 isolates from group II, six STs were found with more than one isolate (ST225, ST880, ST292, ST359 and ST1813), grouping 38% of the isolates. The diversity indices were similar in the two groups (Simpson's index, 92.3% versus 94.7%, respectively). Fourteen isolates from group I and two isolates from group II belonged to ST225, among which 14 isolates were characterized by antibiotic resistance phenotype 4. ST1479 grouped eight isolates from different geographic regions from group I and one isolate from group II. The eight isolates presented the two similar antibiotic resistance phenotypes 1 and 2 (differing by the presence or absence of a β-lactamase). Of note, the isolate from knee fluid was ST1479. ST880 was represented by two isolates from group I and two isolates from group II, all of which exhibited antibiotic phenotype 4. Antibiotic resistance phenotype 5 (with a reduced susceptibility to ceftriaxone) was observed only in two isolates from group I (ST21 and ST1985). These STs were closely related, since they share the same tbpB allele (allele 33) and their porB alleles differed by two single nucleotide polymorphisms (allele 14 for ST21 and allele 467 for ST1985). Antibiotic phenotype 6 (resistance to tetracycline and ciprofloxacin) was observed only in group II, in five isolates of distinct STs. Notably, the genetic diversity differed according to the susceptibility phenotype of the isolates. Isolates with antibiotic phenotype 3 (susceptible to all tested antibiotics) were associated with many single STs, whereas a majority (22/31 [71%]) of isolates with antibiotic phenotype 4 (with reduced susceptibility to ceftriaxone and high resistance to ciprofloxacin) were clustered in the STs ST225, ST880, and ST437. In addition, these three STs were closely related, as the allele sequences of tbpB gene were identical (allele 4). Moreover, the por allele of ST225 (allele 4) differed from that of ST437 (allele 14) and ST880 (allele 489) by a single nucleotide polymorphism. These observations indicate a common ancestral origin of these isolates, from which they acquired their phenotype.
CONCLUSION
Finding the fact in crimes against physical integrity is not possible without using forensic techniques. In order to find the fact in every case, there is a set of methods which are usually inter related. Forensic sciences can be used in three main stages; first the establishment of the criminal conduct and its effects, second the determination of the offender and third identification of the victim. The development of scientific means and testing in the context of crime detection has led to a higher quality of forensic techniques; DNA testing is a good example in this respect. However Forensic experts should take into account every trivial thing that may be relevant in the course of the criminal conduct. An examination after rape requires the use of a reliable semen detection test that is sensitive and has very good negative predictive power. Previous studies have shown that cytology allows the detection of some but not all types of sperm up to 72 h whereas a search for acid phosphatases does detect all types of sperm but only in the first 24 h. Regarding the PSA detection kit, it allowed all types of semen to be detected up to 48 h (Schieferstein 1999). The commercialization of rapid detection kits would make the routine search for PSA more viable. There is an excellent concordance between the PSA-Check 1® kit and the spermogram, with very good negative predictive values even at 48 h. In our opinion, the PSA test is the best marker of the presence of semen and is well suited for use in emergency consultations. If necessary, a cytological test could be performed during the consultation if the PSA result were to be negative after 48 h. Rape is indexed as the second-most-frequent violent crime, yet it also is considered the crime that is least reported. Rape is a serious offense against the person, assaulting both body and psyche, and victims may suffer short- or longterm impairment as well. As primary care providers, nurse practitioners are in a position to identify rape victims and begin interventions to alleviate suffering, provide supportive care and plan for follow-up in order to prevent devastating effects on the individual's life. The purpose of this article is to better acquaint nurse practitioners with the scope of rape and rape issues, and the impact rape has on adult female victims and their families. The article discusses the definition of rape; rape myths; prevalence and reporting; responses of practitioners, victims and families; and primary care interventions in the areas of counseling, physical assessment and treatment, and police/legal considerations. And suggested some molecular typing methods to detect presence of N. gonorrheae which is a sexually transmitted disease implanted by accused in victims.
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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524152EnglishN2013January26HealthcareA STUDY OF THE CONDYLAR CANAL AND ITS INCIDENCE, MORPHOLOGY AND CLINICAL SIGNIFICANCE
English6670S. KavithaEnglish A. AnandEnglishThe posterior condylar canal is one among the largest and inconstant emissary foramina in the human skull. The canal, if present, may be single or multiple. It transmits the posterior condylar vein and meningeal branch of occipital artery. The present study was conducted to observe the incidence of posterior condylar canal and its morphological variations in dry adult human skulls. The dimensions and shape of the condylar fossa were also studied. In 78.9 % cases, it shows bilateral presentation where as in 21.1 % cases it presents unilaterally. Single canal or multiple smaller canals in clusters were also observed. Knowledge of such anatomical variations is important in case of treatment of dural arterio venous fistula involving the posterior condylar canal.
EnglishCondylar fossa, canal, foramenINTRODUCTION
The posterior part of the occipital condyles exhibits a depression known as the condylar fossa. The superior articular facet of the atlas is accommodated within this fossa during movements of the atlanto occipital joint. Rarely within this fossa does a foramen be present which is called as the condylar canal or the posterior condylar canal . This foramen can be either unilateral or bilateral and the foramen may or may not be patent. If the foramen is patent, it usually transmits an emissary vein to the sigmoid sinus and nerves which supply the dura mater of the posterior cranial fossa. This emissary vein is called as the posterior condylar vein which connects the veins present in the sub occipital triangle with that of the sigmoid sinus The posterior condylar emissary vein communicates posteriorly with the vertebral venous plexus in the condylar fossa and anteriorly with the jugular bulb or the vein in the hypoglossal canal . The posterior condylar canal may also present itself as a doubled entity . Many canals exist in and around the occipital condyles which are grouped as paracondylar canals . These paracondylar canals when patent transmit emissary veins which can communicate with other veins The posterior condylar canal also transmits meningeal branches of the occipital artery . Anatomically the occipital dural venous sinus inside the falx cerebelli and occasionally it may present as a paired structure. This sinus usually drains into the confluence of sinus which is present close to the internal occipital protuberance and at the junction of falx cerebri and falx cerebelli. The posterior condylar vein which passes through the posterior condylar canal drains into the occipital sinus Compression of structures passing through the foramen can occur during movements of the atlanto occipital joint because the posterior margin of the atlas fits itself into the condylar fossa when the neck is fully extended . Such pressure on neurovascular structures can result in clinical symptoms. However there are reported cases of dural arteriovenous fistulas of the posterior condylar vein The lateral transcondylar approach is a surgical approach for skull base surgery. Particularly this approach involves extensive dissection and may cause injure the neurovascular structures . Many studies exist about the occipital condyles and its variations but there are not many studies about the posterior condylar canal and its variations of Indian ethnicity in literature. Therefore a thorough knowledge of the bony architecture of the posterior condylar canal and its variations is needed to be known before any procedure.
MATERIALS AND METHODS
About 156 human skulls were obtained from the department of Anatomy, Vinayaka Missions Kirupananda Variyar Medical College, Salem for the purpose of study. The equipments used for the purpose of study were hand lens, vernier calipers, measuring tape and digital photography equipment. The parameters studied were presence and absence of the foramina, whether the foramina were unilateral or bilateral, whether the foramina were patent or not, predominance of patency, dimensions of the condylar fossa and any abnormal bony variations in architecture were documented.
Statistical Analysis
Standard deviation, mean values and the range were calculated from the obtained results and parameters measured were evaluated by the paired sample t test to differentiate between the right and the left sides. The resultant p value was less than 0.05 making it statistically significant.
RESULTS
Of the 156 skulls studied, in 09 skulls the foramen was absent bilaterally (Table 1). In the remaining 147 skulls the foramen was present unilaterally in 31 skulls and bilaterally in 116 skulls (Table 2). Among the unilaterally present foramina it was more predominant on the left side (Table 3) and patent foramina were more on the right side (Table 4).Also foramina were not patent more on the right side (Table 5). Multiple foramina were present only in 05 skulls examined (Table 6).The dimensions of the condylar fossa were more on the right side than the left. Variations were also observed in the shape of the condylar fossa and appearance of the foramina (Table 8).
DISCUSSION
The posterior condylar canal is almost a constant entity in the condylar fossa and only in a miniscule percentage the canal is absent making it and the structures traversing through it clinically significant. In the present study, out of a 156 skulls studied, the foramen was absent bilaterally in 5.76% of the skulls therefore the structure is clinically important because the foramen is present in 94.2% and it connects the xtracranial veins with the intracranial dural venous sinuses. In the present study there is preponderance towards bilaterally present foramen (78.9%) and unilateral being (21.1%). Surprisingly when the foramen was unilateral more orientation was shown on the left side (61.3%) than the right (38.7%). Of the examined skulls more number of foramina was patent on the right side (69.5%) than the left (30.4%). In the skulls where the foramina were not patent there is a significant shift to the right (67.2%) than the left side (32.72%). Going by the significant number of patent foramina, planning and execution of any surgical procedure should consider any venous vascular abnormality which can produce serious repercussions intracranially either be it a fistula or a bleed. Planning any invasive procedures in specific cases of dural arteriovenous fistulas, the dimensions of condylar fossa are important for limiting the field of exposure. Of the examined skulls the crescent shaped condylar fossa was the most common (58.9%) followed by oval shaped (34.6%) and oblong shape (6.4%). The measurements of space where the articulation of the atlas takes place the mean length and breadth is more on the right (15mm and 7mm) than the left side (12mm and 6mm). The present study indicates that condylar fossa is broader on the right side than the left side. Surgical approaches to the foramen magnum and the craniocervical junction like the far lateral approach will involve extensive dissection of structures related to the posterior condylar canal and particularly the posterior condylar canal. Findings of the present study will serve as a bench mark as it pertains to Indian ethnicity and thorough knowledge of the surgical anatomy of this region and its reported variations should be disseminated to surgeons who perform difficult and complicated surgical procedures.
ACKNOWLEDGEMENTS
The authors sincerely wish to thank the management, administrators and the Professor and Head of the department of Anatomy of Vinayaka Missions Kirupananda Variyar Medical College, Salem for their whole hearted support and permissions to utilize their resources and conduct this study. The authors acknowledge the great help received from the scholars whose articles cited and included in references of this manuscript. The authors are also grateful to authors/editors/publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed. Authors are grateful to IJCRR editorial board members and IJCRR team of reviewers who have helped to bring quality to this manuscript.
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5. Tuli. A; et al, Incidence, morphology and Clinical relevance of bony canals and vascular grooves in the paracondylar region of adult human skull. J Clin Neurosci. 2008 Jun; 15(6): 689 92. Epub 2008 Apr 10.
6. H. Kiyosue, et al ; Dural Arteriovenous Fistula Involving the posterior condylar canal; Am J Neuroradiol 28: 1599 601, Sep 2007.
7. SanMillan Ruiz D, Gaillound P, Rufenacht DA, et al. The Cranio cervical venous system in relation to cerebral venous drainage. AJNR Am J Neuroradiol 2002; 23: 1500 08.
8. Emel AVCI et al; Anatomical Variations of the foramen Magnum, occipital condyle and Jugular Tubercle; Turkish Neurosurgery 2011, Vol: 21, No: 2, 181 190.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524152EnglishN2013January26HealthcareNEW DRUG TARGETS TO TREAT THE OBESITY
English7182Dabhade SanjayEnglish Dabhade S.S.English Tiwari S.A.English Rane B.T. Meenakshi SableEnglishBackground: The incidence of obesity is increasing dramatically to epidemic proportions. There are few approved anti-obesity pharmacological treatments and their modest efficacy and safety concern. Presently two drugs approved by US FDA for treatment of obesity are Phentermine and Orlistat.
Objective: The aim of this review is to discuss the new pharmacological agents that are under development and that may be eventually used for treatment of obesity.
Low doses of topiramate and phentermine: The rational for combining topiramate with phentermine is to minimise the required dose of each of the medication thereby opening up more than one pathway to satiety in hope of achieving great efficacy.
Bupropion and Naltriaxone: Monotherapy with bupropion shown weight loss of 2.8 kg at 52 weeks and this does not meet FDA criteria for an antiobesity drug. Naltriaxone alone is associated with minimal weight loss. Combination would be associated with weight reduction.
Zonisamide and Bupropion: Zonisamide induces weight loss as a side effect. It was thought that bupropion when added to zonisamide decreases the depressive and sedative properties associated with zonisamide while the latter might reduce the likelihood of bupropion-induced seizures.
Liraglutide: Victoza (liraglutide) is a once-daily version of the new-generation GLP-1(glucagon like peptide) analogs. Victoza reduces body weight and body fat mass through mechanisms involving reduced hunger and lowered energy intake. Cetilistat: an inhibitor of pancreatic lipase, an enzyme that breaks down triglycerides in the intestine. This drug is similar to the currently FDA-approved drug orlistat. Phase III trials of cetilistat are currently under way in Japan.
TTP 435:TTP435 is a potent and selective inhibitor of AgRP. TTP435 was shown to reduce food intake and body weight gain, reduce fat composition, and reduce insulin levels in a dose-dependent fashion.
GSK 598809: GSK 598809 is a D3 antagonist that blocks dopamine. It is thought that blocking dopamine may reduce the intake of foods high in fat and sugar.
Conclusion: Many factors have mitigated against active drug development, including the poor safety and efficacy of previous antiobesity drugs. The new generation of antiobesity drugs offers hope for the management of obesity, although no single agent is likely to be a solution.
Englishphentermine, fenfluramine, orlistat, obesityINTRODUCTION
The incidence of obesity is increasing dramatically to epidemic proportions in almost all societies of the world and with it come the major pathological complications including hypertension, type 2 diabetes.1 DM, osteoarthritis, dyslipidemia, obstructive sleep apnoea and some cancers.2 Many of these diseases can be prevented or ameliorated with a reduction in body weight. Despite dramatic advances in our understanding of central regulation of energy balance and obesity, there are few approved antiobesity pharmacological treatments and their modest efficacy and safety concern.3
Regulatory authorities
European Union: a mean weight loss of 10% from the baseline after 1 year of treatment.
US FDA : >5 % placebo subtracted weight loss difference after 1 year. 4 Obesity is a fetal chronic relapsing disease, the most prevalent of 21st century .Despite rigorous attempts at behavioural change, many patients are unable to achieve long term maintenance of weight loss through lifestyle alone and the growing number of patients forced to undergo bariatric surgery points the need for effective drug treatments.5 So there is need of continuous dialogue between obesity researchers, pharmaceutical industries and regulatory authorities to stimulates research and drug development based on the clinical need of the patients and recognising the true clinical endpoints should be the priority to allow appropriate risk: benefit assessment.6 There are two drugs approved by US FDA for treatment of obesity 7, 3
Phentermine, approved in 1959, is the most commonly prescribed antiobesity agent in the United States.
Orlistat, approved in 1999, is an oral lipase inhibitor that reduces absorption of dietary fat. Orlistat can have significant gastrointestinal side effects, especially if dietary fat intake is much more than 30% of total daily caloric intake; this limits its tolerability in many patients.7
Limitations: valvulopathy: fenfluramine and dexfenfluramine, Abuse potential and psychiatric side effects: rimonabant,
Cardiac adverse events: sibutramine. 8
New targets have been identified as more research has been performed to understand the complex circuitry controlling energy homeostasis. The aim of this review is to discuss the new pharmacological agents that are under development and that may be eventually used for treatment of obesity
Hypothalamus and the central control of feeding and energy homeostasis
The hypothalamus is the key processing area within the brain for the integration of numerous signals related to energy homeostasis. Peripheral signals of satiety are integrated and passed on to other areas of the brain via nuclei in the hypothalamus
Circuits implicated in the central control of feeding. AcbSH, nucleus accumbens shell; AgRP, agouti gene-related peptide; ARC, arcuate nucleus; CART, cocaine-amphetamine regulated transcript; CCK, cholecystokinin; CRH, corticotrophin releasing hormone; LHA, lateral hypothalamus; α-MSH, alpha-melanocyte stimulating hormone; MCH, melanin-concentrating hormone; MC4R, melanocortin 4 receptor; NPY, neuropeptide Y; NTS, tractus solitari; ORX-orexin (hypocretin); OXY, oxytocin; POMC, pro-opiomelanocortin; PVN, periventricular nucleus.
Peripheral signals from adipose stores, the gastrointestinal tract and endocrine system influence the activity of neurons within the arcuate nucleus of the hypothalamus. When fat stores are reduced and energy levels are low, hunger signals mediated via an increase in the gut hormone, ghrelin, and reductions in insulin, glucose, leptin and cholecystokinin (CCK) cause increases in the activity of both neuropeptide Y (NPY) and agouti-related protein (AgRP) neurons, which in turn leads to decreased activity of the melanocortin system, leading to disinhibition of melanin-concentrating hormone (MCH) and orexin (ORX) signalling producing a marked orexigenic effect. Following a meal the reverse occurs, with high levels of glucose, insulin, CCK and reduced ghrelin levels leading to increases in pro-opiomelanocortin (POMC), in turn increasing α-melanocyte-stimulating hormone (α-MSH) release and decreasing MCH/ORX activity, leading to satiation and a termination of feeding.6
Combination Therapy
Low doses of topiramate and phentermine (Qnexa): Phentermine, an amphetamine derivative, has been on the market for more than 30 years for short-term treatment of obesity. Topiramate has been approved for migraine prophylaxis and the treatment of seizure disorders. Early studies of topiramate, when used for other indications, demonstrated an unexpected weight-loss benefit. Topiramate is a weak carbonic anhydrase inhibitor, inhibits isoforms II and IV; it also modulates GABA –A receptors which causes inactivation of Na channels. The modulation of γ-amino butyric acid may have a role in the reduction of food intake.9 The rational for combining topiramate with phentermine is to minimise the required dose of each of the medication thereby opening up more than one pathway to satiety in hope of achieving great efficacy. In oct.2010 ,the FDA did not approved QNEXA because of the elevated heart rate associated with its use , teratogenic potential of drug .In Jan. 2011 VIVUS announced that FDA had requested additional information regarding teratogenecity and company will continue to work with FDA in an effort to secure approval. VIVUS has completed three Phase III studies of Quinexa. Results of this trial are given in the table.
Bupropion and Naltriaxone (Contrave)
A dual antiobesity agent .It is combination of bupropion and naltriaxone. Buproprion is inhibitor of DA and NA used for treating depression and inducing smoking cessation. During initial trials it was noted that it suppressed appetite and food craving. Monotherapy with bupropion shown weight loss of 2.8 kg at 52 weeks as single agent and this does not meet FDA criteria for an antiobesity drug.10 As monotherapy naltriaxone is associated with minimal weight loss.3 Thus combining these two agents would associate with clinically meaningful and sustained pattern of weight reduction.
In a double-blind placebo-controlled study, enrolling 419 obese subjects BMI 30–40 kg/m2 g over a period of 24 weeks. The subjects were receiving one of the following: Placebo, Naltrexone 48 mg alone, Bupropion slow-release (SR) 400 mg alone, or combinations of Bupropion 400 mg with varying doses of Naltrexone (16 mg, 32 mg, and 48 mg). 11 At 24 weeks, the average weight loss in each of the groups was as, 0.9 kg 1.1 kg; 2.6 kg; for alone drug and With (400 mg Bupropion) + (Naltrexone 16 mg, 32mg, 48mg, ) 5.1 kg; 5.1 kg, and 4kg respectively. At a 48-week extension time point, the weight loss increased to 7.4 kg, 8.2 kg, and 10 kg, respectively, in the three combinations treatment groups. These data endorse the hypothesis that two drugs working synergistically and in combination provide greater weight loss than either of them singly.
Zonisamide and Bupropion (Empatic)
Empatic is the combination drug of zonisamide and bupropion. Clinically, it has been shown to induce weight loss as a side effect. However, a possible mechanism is sodium channel modulation and enhancement of dopamine and serotonin neurotransmission, potentially resulting in weight loss. Bupropion, has also been linked to weight loss. With this drug, the weight loss is thought to be caused by a drug-induced increase in the level of dopamine, which could lead to a reduction in appetite. 12 The addition, it was thought that bupropion when added to zonisamide decreases the depressive and sedative properties associated with zonisamide while the latter might reduce the likelihood of bupropion-induced seizures. 7 In September 2009, Orexigen released data from a 24-week phase IIb double-blind, placebocontrolled trial of Empatic in 729 obese patients with BMI range 27–45 kg/m2 . The patients were randomized to one of six arms: Two groups: 1) Bupropion IR 360 mg + Zonisamide SR 120 mg 2) Bupropion IR 360 mg + Zonisamide SR 360 mg, Three single-treatment groups 1) Bupropion IR 360 mg, 2) Zonisamide SR 360 mg, 3) Zonisamide SR 120 mg and 4) Placebo. The combination therapy containing zonisamide 120 mg, 360mg given weight loss of 6.1% and 7.5%. No patient experienced serious adverse events due to Empatic. The occurrence of depression, impaired cognitive function, anxiety, and suicidality were not significantly different between the placebo and Empatic groups. Plans for phase III Empatic trials have not yet been announced.
Pramlintide/metreleptin
Leptin is a hormone produced by adipocytes, and early studies linked leptin deficiency in mice leads to massive obesity. At first here was hope that leptin would be a successful treatment option to combat obesity. However, many clinical trials failed to demonstrate any benefit of treatment with recombinant human leptin. In fact, leptin levels have been shown to be up to 10-fold higher in obese individuals. Amylin is a peptide hormone with both glucoseregulatory and anorexigenic actions. Amylin is stored in the pancreatic A-cell secretory vesicles and secreted in response to food intake. It acts in the hindbrain area postrema and central nucleus of the amygdala to reduce food intake, by acting as a satiety signal. 2 Clinical studies have shown that pramlintide, (Synthetic amylin) currently approved in the United States for the treatment of type 1 or 2 diabetes, leads to reduction in food intake and body weight in obese humans.13 The results of mechanistic studies in rats pretreated with amylin suggested that leptin signaling within the hypothalamus and caudal hindbrain may modulate the observed weight-loss synergy, such the presence of amylin may “prime” the hypothalamus to respond better to leptin. In a 28-week, double-blind, placebo-controlled study enrolled 608 obese BMI 27–45 kg/m2 . After a 1-week placebo lead-in period, the subjects were randomized to twice-daily therapy with eight regimens: (i) placebo + placebo, (ii) pramlintide 360 µg + placebo, (iii) metreleptin 5 mg + placebo, (iv) pramlintide 180 µg + metreleptin 2.5 mg, (v) pramlintide 180 µg + metreleptin 5 µg, (vi) pramlintide 360 µg + metreleptin 1.25 mg, (vii) pramlintide 360 µg + metreleptin 2.5 mg, or (viii) pramlintide 360 µg + metreleptin 5 mg. The magnitude of the weight loss was found to be dependent on dose and baseline BMI. Treatment with the highest pramlintide + metreleptin doses had an average weight loss of 11% (P < 0.01), when compared with placebo group (1.8%) and in the groups that received either of the agents singly.
Monotherapy in Phase II/III Trials
Lorcaserin Lorcaserin is a 5HT-2C receptor agonist. Fenfluramine, a previously marketed non selective 5HT agonist, was highly successful in inducing weight loss. Fenfluramine targeted 5HT-2C in addition to 5HT-2B and 5HT-2A. It has been seen that 5HT-2A receptors are hallucinogenic14 where as 5HT-2B receptor activation is associated with the development of valvulopathy and primary pulmonary hypertension. Lorcaserin have a high affinity for the 5HT-2C subtype and very less for 5HT-2A and 5HT-2B; therefore become a target of interest. DM patients who were overweight or obese. (N=604)
In January 2011, the manufacturer of the drug announced that discussions with the FDA to finalize protocols for action designed to address the issues raised by the FDA, and that it hopes to resubmit the new drug application for lorcaserin by the end of 2011.
Liraglutide: GLP-1 is a humoral gut peptide that improves insulin secretion, and the currently available analogs have been approved for the treatment of diabetes. GLP-1 also delays gastric emptying and suppresses appetite, resulting in decreased energy intake and weight loss. Exenatide and liraglutide are FDA approved GLP-1 analog given DM. In a double-blind placebo-controlled 20-week trial with open-label orlistat comparator in 19 sites in Europe. 564 individuals were randomly assigned, to one of four liraglutide doses (1·2, 1·8, 2·4 or 3·0 mg, n=90-95) or to placebo (n=98) administered once a day subcutaneously, or orlistat (120 mg, n=95) three times a day orally. All individuals had a 500 kcal per day energydeficit diet, including the 2-week run-in. An 84- week open-label extension followed.15 Mean weight loss with liraglutide was 4·8 , 5·5 , 6·3 , and 7·2 kg respectively as compared with 2·8 kg and 4·1 kg with placebo and orlistat. Nausea and vomiting more in liraglutide than in placebo, but mainly transient and rarely led to discontinuation of treatment. "This is one that is fulfilling a true medical need in the field of medical obesity -- where people are either very obese, or are obese and have prediabetes or other metabolic disturbances," Krogsgaard said. Victoza (liraglutide) is a once-daily version of the new-generation GLP-1 type of drug which stimulates cells to release insulin when blood sugar levels are high.
Semaglutide, a once-weekly GLP-1 analogue, Semaglutide, is based on a different molecule than Victoza, has finished phase II trials. Taspoglutide, under development by Roche Holding AG and Ipsen SA, is another GLP-1 drug for type-2 diabetes.16 Novo Nordisk remains committed to the development of a longer-acting GLP-1 analogue. Victoza lowers blood glucose by stimulating the release of insulin and lowering of glucagon secretion when blood sugar levels are high and also by slowing gastric emptying. Victoza also reduces body weight and body fat mass through mechanisms involving reduced hunger and lowered energy intake. Victoza is a once-daily injection taken any time of day independent of meals.
Cetilistat: Is an inhibitor of pancreatic lipase, an enzyme that breaks down triglycerides in the intestine. This drug is similar to the currently FDA-approved drug orlistat. orlistat's gastrointestinal side effects are a principal cause for discontinuation, cetilistat may become a preferred lipase inhibitor for achieving weight loss. Phase III trials of cetilistat are currently under way in Japan. Evidence of the safety and efficacy of cetilistat has been established through extensive Phase I and Phase II clinical trials in Europe, the US and Japan in over 1,000 subjects (over 800 subjects on active drug). In a second Phase IIb study involving 612 clinically obese diabetic patients, along with weight loss Cetilistat was also shown to cause statistically significant reductions in HbA1c. Furthermore, the proportion of subjects discontinuing treatment for adverse events was lower with cetilistat than with placebo and with Orlistat, confirming earlier studies showing that cetilistat has a superior tolerability profile. Cetilistat has begun a Phase III trial in Japan. 17
Tesofensine: Tesofensine is a triple monoamine reuptake inhibitor that blocks the reuptake of 5HT, DA, and NA.Originally, this drug was developed for the treatment of Alzheimer's and Parkinson's diseases, and it was noted in clinical trials that there was a persistent weight loss in patients . The drug is believed to induce weight reduction through both appetite suppression and increased thermogenesis. A phase II proof-of-concept study was conducted by Astrup and colleagues. This randomized, double-blind, placebo-controlled study enrolled 203 subjects with baseline BMI 30–40 kg/m2 . The subjects were randomized to receive 24 weeks of treatment with tesofensine 0.25, 0.5, or 1 mg, or placebo, after a 2-week run-in period. Analysis demonstrated that the weight reductions were dose-dependent.The weight losses of 4.7, 9.1, and 10.6 kg, respectively. Adverse effects of tesofensine include dry mouth, nausea, dizziness, constipation, and abdominal pain. There was a notable dose-dependent increase in heart rate up to 8.5 beats per minute at the highest dose (1.0 mg). In addition, there was a 1–2 mm Hg increase in blood pressure that was not statistically significant. Given these findings, further phase III trials might limit the dose to 0.25 and 0.5 mg so as to reduce the impact on heart rate and blood pressure.18 Preclinical data from diet-induced obese rats supported the hypothesis that tesofensine reduces body weight. In phase II clinical trials with tesofensine in obese individuals, dose-related reductions in body weight, body fat and waist circumference, as well as improvements in other obesity-related endocrine factors, were observed. Neuro Search has decided that a phase 3 program including two obesity studies of one year each is the best way to proceed. This phase 3 program must also include a study for more than a two year period in order to determine the drug's cardiovascular safety profile.
Velneperit: NPY (neuropeptide Y) stimulates food intake, inhibits energy expenditure, and increases body weight by activating the hypothalamic NPY receptors Y1 and Y5.Velneperit, a once-daily, oral neuropeptide Y5 receptor antagonist, blocks the binding of centrally acting NPY to its Y5 receptor, thereby controlling energy balance and food consumption.
In a double-blind, multi-center , randomized, parallel-group study to assess the efficacy and safety of 400 mg of velneperit (S-2367) and 120 mg of orlistat administered Individually or combined orally three times per day with a reduced calorie diet (RCD) in obese subjects . Results of this trial are same as of orlistst in relation to weight loss.20 Shinogi has completed the phase II trials, and planning for phase III trials is under way.
Obinepitide: Obinepitide is a synthetic analogue of two naturally occurring human hormones: PYY3-36 and pancreatic polypeptide. These hormones are normally released during a meal and are known to play a role in the regulation of food intake and appetite, acting as satiety signals. Initial studies in humans have shown that infusion of PYY3-36 reduced food intake in both obese and lean subjects. Obinepitide's unique characteristic is that it targets both the Y2 and Y4 receptors without showing an affinity for the Y1 receptor and Y1 receptor is associated with cardiovascular side effects. In March 2006, 7TM Pharmaceutical announced positive results from obinepitide's proof-ofconcept phase I/II study. Subcutaneous injections of once- and twice-daily obinepitide were well tolerated and inhibited food consumption for up to 9 hrs. after drug administration relative to placebo. Obinepitide is under development.
Early-Phase Drugs (Phase I)
TTP 435: Agouti-related protein (AgRP) is a neuropeptide produced in the arcuate nucleus of the hypothalamus. It is coexpressed with NPY and works by increasing appetite and decreasing metabolism and energy expenditure. TransTech Pharmaceutical identified TTP435 as a potent and selective inhibitor of AgRP. In vivo, TTP435 is orally bioavailable, with high brain penetration. In several studies of animal models of obesity ranging in duration from overnight administration to 4-week treatment, TTP435 was shown to reduce food intake and body weight gain, reduce fat composition, and reduce insulin levels in a dose-dependent fashion. TTP435 is currently being assessed in obese subjects in phase II clinical trials
ZGN-433: ZGN-433 is a methionine aminopeptidase 2 inhibitor. Originally developed as a treatment for solid tumors, it was initially thought to block angiogenesis and reduce adipose tissues by blocking blood supply. However, that administration of the drug caused profound weight loss in mice, which thereafter achieved ideal body weight. The drug may play a role in altering the mechanism by which the body metabolizes fat. In dogs receiving ZGN-433,
weight loss is associated with improved glycemic control and an apparent reduction in demand for insulin secretion. In January 2011, Zafgen reported positive results from its phase Ib study using ZGN-433. A double-blind, placebo-controlled, multipleascending-dose study was performed in women with BMI 32–35 kg/m2 , with 24 subjects enrolled in the core study. Primary objective: to evaluate the safety and tolerability of the compound. Second objective: to obtain information on weight loss in subjects exposed to eight doses of IV ZGN-433 administered over 4 weeks. Subjects receiving ZGN-433 had a reduction in median body weight of 1 kg per week and 3.1% of initial body weight over 26 days. In addition, there was a decline in hunger, 38% reduction in triglyceride levels, and 23% reduction in LDL cholesterol. Zafgen plans to initiate phase IIa studies in 2011.21 PP 1420: PP 1420 is a pancreatic polypeptide analog that is thought to increase satiety. Previous studies of PP1420 have shown that injections of human PP have the effect of reducing appetite and food intake. Human PP has a short half-life. PP 1420 is a synthetic form of PP with a longer half-life. Phase I trials have been completed by Wellcome Trust, but the results have not yet been released.22
GSK 598809: GSK 598809 is a D3 antagonist that blocks dopamine. It is thought that blocking dopamine may reduce the intake of foods high in fat and sugar, and may be a potential treatment option for compulsive overeaters and/or binge eaters. The medication is being developed for the treatment of substance dependence and other impulsive disorders. GlaxoSmithKline is currently completing phase I study designed to examine the behavioural and physiological effects of a single dose of GSK 598809 on food reward and reinforcement in relation to foodseeking behaviour under conditions of fasting, using neurocognitive and metabolic end points in subjects with obesity. The study was scheduled to be completed in mid-2011; no further data have been released
Ezlopitant: Ezlopitant is a neurokinin receptor-1 antagonist that has been implicated in both learned appetitive behaviours and addiction to alcohol and opioids. Recent evidence from rodent studies suggests that ezlopitant reduces the appetite for sucrose, thereby decreasing the consumption of sweetened foods and drinks. It has been suggested that sweet foods and drinks can be addictive in the same way as alcohol; this drug may therefore have a role in obesity treatment. Further studies have yet to be done.23 To evaluate the selectivity of the NK1-receptor antagonist in decreasing consumption of sweetened solutions, they compared the effects of ezlopitant on water, saccharin-, and sodium chloride (NaCl) solution consumption. Ezlopitant decreased intake of saccharin, but had no effect on water or salty solution consumption.
Thyroid hormone receptor agonists
Thyroid hormone affects in a myriad of biological processes such as development, growth, and metabolic control. Triiodothyronine (T3) is the biologically active form of thyroid hormone that acts through nuclear receptors, TRα and TRβ, regulating gene expression. The distribution of these receptors is heterogeneous amongst the different tissues, it is not surprising that some physiological effects of T3 are isoform specific. For example, while TRα is the dominant receptor in the brain and skeletal system and mediates most of the synergism between T3 and the sympathetic signaling pathway in the heart, TRβ is abundant in liver and is probably the isoform that mediates most of the T3 effects on lipid metabolism. Thus, it makes sense to develop compounds that selectively act on either one of the TRs, allowing for the activation of specific T3-dependent pathways. The available studies indicate that achieving selective activation of different TR-mediated pathways is a promising strategy for treating lipid disorders and obesity.
GC-1, a selective TRβ agonist, when administered to rats, demonstrated a normalization of serum cholesterol and triglyceride levels. In addition, GC-1 was found to accelerate energy expenditure in rats and lower body weight in primates without cardiac side effects. The accelerated metabolic rate was followed by a decrease in fat but not in lean mass. In other studies, KB2115, a selective TRβ agonist, was administered to moderately overweight and hypercholesterolemic human subjects. It was found to be safe and well tolerated, and it caused a 40% lowering of both total and LDL cholesterol. Phase II trials are under way to investigate the efficacy of TRβ receptor agonists in treating dyslipidemia, but they may become a potential target for antiobesity treatment soon 24
11β-HSD1 inhibitor: 11β-HSD1 is a bidirectional enzyme that interconverts hormonally inactive cortisone to cortisol. Preclinical animal studies have shown proof of concept, with improved glucose tolerance and weight reduction reported in many diabetic and obese mouse models treated with 11β-HSD1 inhibitors. Phase I and II clinical data reported at the American Diabetes Association's Scientific Sessions in June 2008 were equally encouraging.25
PPAR gamma (ϒ): PPAR ϒ plays a major role in differentiation of preadipocyte to adipocyte, the process of adipogenesis. Thus PPAR ϒ agonists like pioglitazone enhance differentiation of adipocyte which caused weight gain in animals and humans. PPAR modulators are to develop agents that modulate PPAR ϒ in such a way that the compounds improve insulin sensitivity without any promotion of weight gain. Another approach to try to overcome the increase in body weight seen with full PPAR ϒ agonists is to develop agonists that act on two or all three of the PPARs, the hypothesis stimulating PPAR δ, PPAR ϒ will activate fatty acid activation and cancel out the adipogenic effects of PPAR ϒ agonism.26
PPAR-γ coactivator-1 α: Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α is a member of a family of transcription coactivator that plays a central role in the regulation of cellular energy metabolism. It is strongly induced by cold exposure, linking this environmental stimulus to adaptive thermogenesis. It participates in the regulation of both carbohydrate and lipid metabolism. It is highly likely that PGC-1α is intimately involved in disorders such as obesity, diabetes, and cardiomyopathy. Its regulatory function in lipid metabolism makes it an inviting target for pharmacological intervention in the treatment of obesity and Type 2 diabetes.27 PGC-1α also interacts with other nuclear hormone receptors such as PPAR-α, retinoic acid receptor, and thyroid receptor in BAT to enhance the expression of brown fat-specific uncoupling protein 1 (UCP1) . UCP1 action leads to dissipation of the proton gradient and the uncoupling of oxidative phosphorylation, thereby increasing heat production.
Metformin: Metformin is a biguanide that is approved for the treatment of diabetes mellitus, a disease that is exacerbated by obesity and weight gain. Although, the cellular mechanism for the effects of metformin are poorly understood. It has three effects at the clinical level---
1) It reduces hepatic glucose production, which is a major source of circulating glucose.
2) It reduces intestinal absorption of glucose, which is a second source of circulating glucose.
3) It increases the sensitivity to insulin, thus increasing peripheral glucose uptake and utilization. Metformin has been associated with significant weight loss when compared to sulfonylureas or placebo. Campbell et al. compared metformin and glipizide (Mylan, Morgantown, WV) in a randomized double-blind study of Type II
diabetic individuals who had failed on diet. The 24 subjects receiving metformin lost weight and had better diabetic control of fasting glucose and glycohemoglobin than did the glipizide group. 28 In a double-blind placebo-controlled trial in subjects with the insulin resistance syndrome, metformin also increased weight loss. Fontbonne et al. reported the results from the BIGPRO study, a 1-yr French multicenter study that compared metformin with placebo in 324 middleaged subjects with upper body obesity and the insulin resistance syndrome. The subjects on metformin lost significantly more weight (1–2 kg) than the placebo group. Although metformin may not give enough weight loss to receive an indication from the USFDA for treating obesity, it certainly deserves consideration in obese Type II diabetic individuals who have failed diet and exercise treatment for their diabetes, and it has been used in children .29
CONCLUSION
The vast gap in the current pharmacological treatment options for obesity is surprising given the high prevalence and economic burden of obesity. Many factors have mitigated against active drug development, including the poor safety and efficacy of previous antiobesity drugs. However, compelling targets are now on the horizon .The new generation of antiobesity drugs offers hope for the management of obesity, although no single agent is likely to be a panacea. If sustained success is to be achieved, obesity will need to be managed like many other chronic diseases, with combination therapies and longterm treatment.
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23. Steensland P, Simms JA, Nielsen CK, Holgate J, Bito-Onon JJ, Bartlett SE.The neurokinin 1 receptor antagonist, ezlopitant, reduces appetitive responding for sucrose and ethanol. PLoS One. 2010 Sep 1;5(9). pii: e12527.
24. Ribeiro MO.Effects of thyroid hormone analogs on lipid metabolism and thermogenesis. Thyroid: 18(2):197-203, Feb 2008/
25. Paul M. Stewart,Jeremy W. Tomlinson. Selective Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1 for Patients with Metabolic Syndrome .Is the Target Liver, Fat, or Both?
26. Am. society for pharmacology and experimental therapeutics vol .70 no 3 ,2006,779-785
27. Huiyun Liang and Walter F. Ward PGC-1α: a key regulator of energy metabolism .Adv Physiol Educ 30:145-151, 2006© 2006 American Physiological Society
28. Expand+Kara M. Levri, , Elizabeth Slaymaker, , Allen Last, Juli Yeh, Jonathan Ference, Frank D’Amico, Stephen A. Wilson Metformin as Treatment for Overweight and Obese Adults: A Systematic Review: Ann Family Med September 1, 2005 vol. 3 no. 5 457-461
29. Min Hae Park, Sanjay Kinra,Kirsten J. Ward,Billy White ,Russell M. Viner, Metformin for Obesity in Children and Adolescents: A Systematic Review, Diabetes Care. 2009;32(9):1743-1745.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524152EnglishN2013January26HealthcareRISK FACTORS FOR BREAST CARCINOMA: A CASE CONTROL STUDY, CENTRAL INDIA
English8393Namrata ThakurEnglish Arun HumneEnglishBackground: The upward trend in breast cancer globally and in India has become a matter of great concern. Breast cancer is the most common site-specific cancer in women. Geographical variations in incidence and mortality rates of breast cancer suggest the known risk factors for breast cancer may vary in different parts of the world and that environmental factors are of greater importance than genetic factors. It is important to identify these factors in order to bring down the incidence, morbidity and mortality due to this disease.
Aim: To study some risk factors associated with breast carcinoma and to assess their strength of association. Setting,
Design and Period: This was a case control study carried out in Government Medical College, Nagpur from August 2010 to February 2011. Material and Methods: we have studied 240 women which included 120 histopathologically confirmed cases of breast carcinoma and 120 age (?5 years) and residence (rural / urban) matched controls. The risk factors studied were religion, education, socioeconomic status, diet, marital status, age at marriage, age at menarche, parity, age at first childbirth, duration of breastfeeding, use of oral contraceptive pills, age at menopause, duration of reproductive life, hormone replacement therapy, exposure to radiation, previous benign breast condition, family history and time since initiation of breastfeeding after delivery.
Results and conclusion: After adjusting with known risk factors, the strongest risk was observed in women having past H/O breast condition followed by Bouddha religion, age at menarche < 14 years, cumulative duration of breastfeeding ? 36 months, upper socioeconomic status and duration of reproductive life > 30 years.
Englishbreast carcinoma, risk factors, case control, India.INTRODUCTION
Urbanization, industrialization, changes in life style, population growth and ageing all have contributed for epidemiological transition in the country. The absolute number of new cancer cases is increasing rapidly, due to growth in the size of the population and increase in the proportion of elderly persons because of improved life expectancy following control of communicable diseases.2 Breast cancer is the most common site-specific cancer, and is the leading cause of death from cancer in women.3 Breast cancer incidence has been increasing in the general population all over the world and particularly in areas of low incidence such as Asia.4Breast cancer is second to cancer of the cervix among women in India. Cancer of the breast has replaced cancer of the cervix as the leading site of cancer in all urban PBCRs, except Chennai.5 The incidence of cancer varies substantially according to age, sex, socioeconomic status (SES), race or ethnicity, geographic location, and time period. These variations have provided strong evidence that much of cancer is caused by environmental factors and is potentially avoidable.6 Another well established risk factor is a family history of breast cancer. Ovarian hormones, particularly estrogens, play a major role in breast cancer development. Many of the other established risk factors are surrogate measures of a woman’s cumulative exposure to estrogen and possibly, progesterone. These include early age at menarche, late age at menopause, nulliparity or late age at first birth, lack of or short-term breast-feeding, alcohol intake of at least one drink per day, obesity after menopause, and long-term use of hormone replacement therapy (HRT) 7 . The effects of diet on breast cancer risk still are being debated.8 It is important to identify these factors to bring down the incidence, morbidity and mortality due to this disease. Only few epidemiological studies have been conducted to determine the risk factors of breast cancer in Indian women. In central India they are even less. Hence, this study was undertaken to review the breast cancer patients at a tertiary care center with respect to their sociodemographic characteristics and risk factors that contributed to develop the disease.
METHODOLOGY
A retrospective case-control study was conducted to assess the relationships between some clinicosocial variables and breast cancer risk in central India. Cases comprised of 120 histologically confirmed female breast cancer patients who presented in the inpatients and outpatients departments of Oncology from August 2010 to February 2011. Control subjects were matched one for one with age (? 5 years) and place of residence (rural or urban). They were selected from the community. The controls for urban cases were selected from field practice area of urban health training centre of study institution. For rural cases, to get controls the nearest Taluka was selected purposively. There are 4 PHCs in the selected Taluka. Out of that one PHC was selected by simple random sampling by lottery method. In the selected PHC, there are 7 subcentres. Out of that, one subcentre was selected by simple random sampling by lottery method. The eligible women were then examined clinically in their home ensuring privacy and those without lump in breast were selected as controls. Those with a palpable lump were referred to our tertiary care centre for further investigation and management. Exclusion criteria for controls were those with known malignant diseases, those who are pregnant or who are lactating their offsprings. A structured questionnaire was prepared in English and in-person interviews were conducted for both cases and controls. Written informed consent was taken from every patient. The questionnaires were divided into several sections comprising socio-demography, reproductive history and established and potential risk factors for breast cancer. Age at menarche was defined as the chronological age when the woman first had her menses. Menopausal status was defined when there have been no menses for a year (natural menopause) 9 or those undergone hysterectomy. Age at first full-term pregnancy was defined as the age of the woman at the last date of her first pregnancy that extended into completed 28 weeks, regardless of the outcome of the pregnancy. Socioeconomic status for urban and rural study subjects was assessed by modified Kuppuswamy’s classification and B G Prasad’s classification respectively. For purpose of analysis, socioeconomic status I was labeled for study subjects belonging to Class I of Prasad’s Classification and Upper Class of Kuppuswamy classification; socioeconomic status II was labeled for study subjects belonging to Class II of Prasad’s Classification and Upper Middle Class of Kuppuswamy classification; and so on. The sample size was based on OR for age at first full term birth ? 25 years of 2.59 with case: control = 1:1. A sample size of 232 was calculated including 116 subjects in each group with 80% precision and 95% confidence. The actual sample studied was 240 (120 per each group).10 All data entry and analyses were conducted using STATA 10.1, 2009. Means and standard deviations (SD) for continuous variables and frequencies and percentages for categorical variables were calculated. Differences of proportions between cases and controls for categorical variables were analysed by simple conditional logistic regression.Crude odds ratios (OR) for variables in the model were drawn from simple conditional logistic regression. The level of significance was set at p < 0.05 for all hypotheses tests in this study. Significant predictors for breast cancer were determined using multiple conditional logistic regression analysis in order to control possible confounders. All variables found significant at alpha=0.02 were included in the saturated model of multivariate analysis. All possible risk factors were independent variables and cases and controls were the dichotomous binary outcomes. The analysis was started by removing the largest p-value one at a time. The adjusted odds ratios were estimated with 95% confidence intervals (CI).
OBSERVATIONS
Table I shows the socio-demographical characteristics of the subjects. There were no significant differences in education level and dietary habits between cases and controls. Buddhist women and those with higher education were at risk of breast carcinoma than others. Table II shows the reproductive characteristics of the subjects. Age at marriage, age at menarche, parity, age at 1st childbirth, duration of breastfeeding, duration of reproductive life were found to be significant. From the figure 1 it is clearly evident that as age at menarche increased, risk of developing breast carcinoma decreased. Thus a declining trend between age at menarche and risk of breast carcinoma was observed, value 0.0001 The declining trend between parity and risk of breast carcinoma is clearly evident from the figure 2. The figure 3 shows rising trend between age at first childbirth and risk of breast carcinoma. As the age at first childbirth increases, the OR for breast carcinoma increases. 19.744, p value 0.0001 Table III shows the results of multiple conditional logistic regression analysis of risk factors of female breast cancer. After adjusting with known risk factors, the strongest risk was observed in women having past H/O breast condition, AOR = 8.43 (1.70-41.75); followed by Bouddha religion, AOR = 4.41 (1.74-11.14). Next stronger risk factors were age at menarche < 14 years, AOR = 4.00 (2.09 – 7.66); cumulative duration of breastfeeding ≤ 36 months, AOR = 2.60 (1.34 – 5.04); upper socioeconomic status, AOR = 2.48 (1.31-4.70) and duration of reproductive life > 30 years, AOR = 2.13 (1.03 – 4.40). Thus all the above mentioned factors had independent risk of their own in development of breast carcinoma and the AOR indicated the respective strength of the risk. Only one case has received hormone replacement therapy. Also only 4 cases and 1 control had family history of breast cancer, hence their association with breast carcinoma could not be assessed.
DISCUSSION
Much of the increase of breast cancer in India has been associated with greater urbanization and changing life styles. The rural: urban case ratio in present study reaffirms the fact that this disease is no longer confined to an urban setting. Amongst the well established risk factors for breast carcinoma, only past H/O breast condition, early menarche, no or less duration of breastfeeding, upper socioeconomic status and longer duration of reproductive life were significantly associated with higher risks of breast cancer in this study. Although several variables, such as age at marriage, parous after 23 years old, were significant in univariate analyses, they were not found significant in multivariate analysis. Traditionally, women in India would marry in their mid-teens; bear children at earlier ages and breastfeed their children for long periods, which were protective lifestyles against breast cancer. There is an increasing trend to abandon these traditional habits of reproduction. There are increasing occupational and tertiary educational opportunities for women that influence their marital status and childbearing. Many have postponed marriages or having children and some may not be able to get partners at all and remained childless. The number of children the women had and the age they had their first child were related closely to each other. Those who had their first child at earlier ages tend to have more children than those who had their first child at later ages. The marrying age of women has an influence on their fertility, namely the number of children and age at first birth of these women. If this pattern of reproductive behavior is not monitored, there will be an increasing proportion of women with reproductive risk factors of breast cancer that will lead to a higher incidence of breast cancer. Buddhist women were at a greater risk of developing breast carcinoma than Hindu women. While Muslim and other religion were not having any significant risk. However as in this study cases were taken from hospital; a community based study is further needed to generalize the finding. It is a known fact that the disease risk is high among Parsi women mainly due to certain favorable risk factors such as late age at marriages, lack of breastfeeding and nulliparity or low parity.11 Only one case was Parsi in the present study this may be because, Parsis usually belong to higher socioeconomic group and hence they may not be attending government hospitals. In our study, it was observed the risk of developing breast carcinoma did not vary significantly as far as the level of education is concerned. Similar findings were noted by Montazeri A et al 12, Norsa’adah B et al 13 , Ebrahimi M et al .14 Although few authers1,15,16 have found that higher education was a significant risk factor for breast carcinoma. Delayed marriage and tendency to have small family in high educated women might explain the risk in high educated women. In the present study it was noted that women belonging to upper socioeconomic status were at a risk of developing breast carcinoma than women in lower socioeconomic status. Findings are consistent with other studies 15,17 . The risk level for non-vegetarians was higher than for vegetarians, but the difference was not statistically significant. Vegetarians who totally avoid animal meat, fish and poultry products generally consume less fat than non-vegetarians. In this context, the odds ratio was expected to be higher among the non-vegetarian group than among the vegetarian group since a diet with a high animal fat intake has been shown to increase the risk of breast cancer. Further studies are required to identify the association of dietary factors in breast cancer. When the group of married women was compared against others, no significant association was found between marital status and risk of breast carcinoma. The findings are consistent with other authors 2,12,13,14,20 . Jussawala D J et al 11 had noticed higher risk of breast cancer in unmarried women. Although association of breast cancer with unmarried state is well known, the finding in present study may be due to fact that, the number of unmarried women in the present study was less. In the present study, the mean age at marriage of cases (19.83 yrs) was found to be significantly higher than the mean age at marriage of controls (18.72 yrs). In the present study, out of 117 married cases, 48 (41.03%) were married on or before 18 yrs and 64 (53.33%) controls were married on or before 18 yrs. Women married at or after 23 yrs were at highly significant risk of developing breast carcinoma than those married before that. Similarly Meshram II et al 2 found that 82.18% cases and 90.38% controls were married at or before 20 years old. The risk was found to be 2.04 times higher in women married after 20 yrs of age than those before. Also, the findings are consistent with Rao D N et al 20 , Gajlakshmi C K et al 21 . In the present study, Women who attained menarche at > 14 yrs were at significant decreased risk of breast carcinoma as compared with those attaining it between 13 -14 yrs. Also a linear decreasing trend was observed between the age of attaining menarche and the risk of developing breast carcinoma. Meshram II et al 2 , Hadjisavvas A et al 22 also had similar findings. However few authors 18,12,14,21 did not find any association between age at menarche and risk of breast cancer. It has been estimated that during most of the 20th century age at menarche has been falling by about 3 months per decade.23 This may contribute to future burden of disease. Nulliparas were at of risk of breast carcinoma compared to parous women,. As the parity increased, risk of breast carcinoma decreased. Meshram II et al 1 and Gajalakshmi V et al 15 had also observed decreasing trend with parity and risk of breast carcinoma. Norsa’adah B et al 13 , Ebrahimi M et al 14 also found protective effect of parity for breast carcinoma. The women who had age at first childbirth < 23 yrs were having significant protection against breast carcinoma. Also there is a rising trend between age at first childbirth and risk of breast carcinoma. Meshram II et al2 Harrison AP et al19 , Gajalakshami V et al15 also had similar findings. However Hadjisavvas A et al22 , Pakseresht S et al18, Montazeri A et al12 had not got such association. The most well established and documented data about endocrinological factors that decrease breast cancer risk are ever having breast fed and longer durations of breast feeding (2, 22, 18, 15) . Many studies showing a longer duration of breast feeding decreases breast cancer risk; findings from present study are consistent with them. The explanation given by Byers T et al26 for protective effect of breastfeeding on breast cancer that process of lactation per se could be seen as somewhat beneficial. This effect could be either direct causing changes within the breast which protect against cancer or indirect via modulation of pituitary and/or ovarian activity and alternatively successful lactation could be seen as an indicator of normally balanced endocrine system and unsuccessful lactation as a correlate of underlying normal imbalance which might cause increased risk of breast cancer. No association was found between initiation of breastfeeding after delivery and breast carcinoma. The milk from the unsuckled breasts had a slightly higher pH27..It has been suggested that an alkaline milieu surrounding epithelial cells plays an important role in carcinogenesis of epithelial surfaces28.An alkaline milieu surrounding epithelial cells causes hyperplasia, cell atypia and a marked increase in mitotic activity, changes which are a prelude to neoplasia. No association was found between H/O oral contraceptive pill use and risk of breast cancer was found in present study. Some Indian 2, 18 and foreign 12, 14 studies also have noted similar findings. However studies by Yavari P et al29 , Daud N A 17 have found increased risk of breast cancer in OC pill users. In the present study, the no significant risk was observed; this may be due to small sample in both cases and controls.
The mean age at menopause was comparable in cases and controls. The findings are consistent with previous authers.18,12,14 However few studies2,21 have got such association. The duration of reproductive life in majority of the study subjects; 65 (54.17%) cases and 83 (69.17%) controls; was 21 – 30 yrs. The women who had the duration of reproductive life ? 30 yrs were at a risk of breast carcinoma than those having it < 30 yrs. The findings of current study are consistent with others2,30 . However Yavari P et al29 have not found such association. No association was found between exposure to chest radiation and risk of breast carcinoma in present study. Although Yavari P et al29 had found such association, it could not be seen in present study because of fewer samples in case and control groups. Women who had history of breast diseases in past were at a significant greater risk for breast carcinoma than those who had not. Our findings are consistent with findings of other authors 2,31 However Daud N A17, Yavari P et al29 have not found such association. No significant association was found between family history of breast cancer and risk of breast carcinoma in present study. Pakseresht S et al18 . Montazeri A et al12, Daud N A17 found that family history of breast cancer was not associated with risk of breast cancer. Many authors 22,12,29,14 had found association between family history of breast cancer and risk of breast cancer. The association may not be evident in present study due to less number of subjects with positive family history. In the present study only one case had ever received hormone replacement therapy. So the association between exogenous estrogen and risk of breast carcinoma could not be assessed. However Daud N A17 has not got such type of association. The major drawback of this study was the reliance on recall and self-reported information. Recall bias was unavoidable, especially for elderly women recalling past events such as age at menarche. However, recall bias of reproductive history was less likely, since factors such as breastfeeding and taking OC were related closely to major events in a woman’s life. Women tended to remember accurately pregnancy-related events and were unlikely to under-report such occasions. As this study was a hospital-based study, there was selection bias in hospital utilisation and the intake of cases, which might not be representative of all women with breast cancer. There is an increased probability of hospitalisation among severe and advanced cases, compared to those with fewer complications and those at an early stage of breast cancer. This might be the reason that majority of cases in this study were at advanced stages. Hospital-based cases represent a selective population because going to a hospital is culturally influenced and dependent upon perception of hospital facilities, reputation, policies and staff competency. Cases and controls were from the same source of population that may have the same probability of exposure, thus improving comparability. Careful criteria were applied to eliminate patients with conditions that shared the same known or potential exposure for breast cancer.
CONCLUSIONS
Factors related to reproductive life like early menarche, late marriage, late childbirth, nulliparity and longer duration of reproductive life are found to be significant risk factors for development of breast carcinoma. Longer duration of breastfeeding is a protective factor for development of breast carcinoma. Women having past history of breast condition are at significant risk of developing breast carcinoma. Bouddha religion and higher socioeconomic status are significantly associated with risk of development of breast carcinoma.
RECOMMENDATIONS
Increasing duration of breastfeeding was found to be protective factor for development of breast carcinoma; hence breastfeeding for a longer duration should be promoted. As women with past H/O breast condition were found to be at greater risk of development of breast carcinoma and the time lag between detection of lump by women and presentation to hospital was high; there is need for health education on self breast examination and early presentation to health facility for better management. Also periodic checkups are recommended for those women with past H/O breast condition
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8. Friedenreich C, Bryant HE, Courneya KS. Case-control study of lifetime physical activity and breast cancer risk. Am JEpidemiol. 2001;154:336–347.
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11. Jussawala D J, Yeole B B, Natekar M V. Histological and epidemiological feature of breast cancer in different religion groups in Greater Bombay. J of Surgical Oncology 1981;18: 269 – 79.
12. Montazeri A, Sadighi J, Farzadi F, Maftoon F, Vahdaninia M, Ansari M et al. Weight, height, body mass index and risk of breast cancer in postmenopausal women: a casecontrol study. BMC Cancer 2008, 8:278
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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524152EnglishN2013January26HealthcareACCURACY OF ULTRASOUND GUIDED FINE NEEDLE ASPIRATION CYTOLOGY IN THE EVALUATION OF THYROID NODULES
English94100Senthil PanneerselvamEnglish Rajan K. VaithianathanEnglish Ramachandran SanthanamEnglishBackground: Thyroid nodules are a common problem which requires an accurate cytological diagnosis for proper management. An essential investigation modality is fine needle aspiration cytology (FNAC) with a sensitivity ranging between 80-90%. Recommendations vary regarding the use of ultrasound in improving the accuracy of free hand fine needle aspiration biopsy. Objective: The aim of our study was to investigate the role and accuracy of ultrasound guided fine needle aspiration cytology in the evaluation of patients with thyroid nodules.
Methods: Forty four patients with nodular thyroid disease who were assessed by ultrasound guided fine needle aspiration cytology (US-FNAC) followed by thyroidectomy were identified. Retrospective analysis of data on the cytology specimens and histological results was carried out.
Results: The sensitivity and specificity of US-FNAC for diagnosing thyroid neoplasms were 91.7% and 93.3% respectively. The diagnostic accuracy was 92.8%, with the rate of inadequate smears as 4.6%.
Conclusions: Ultrasound guided fine needle cytology of thyroid nodules yields more accurate results, with a decrease in the number of inadequate sample category. Precise targeting of lesions in both palpable and non palpable thyroid nodules by the FNA needle under ultrasound guidance will increase the diagnostic accuracy, thereby avoiding or reducing the number of unnecessary thyroid surgeries.
Englishthyroid nodule, ultrasound guided, FNAC, neoplasmINTRODUCTION
Nodular thyroid disease is found in approximately 5% of the population at palpation screening. Routine ultrasound screening of thyroid in clinically normal individuals suggests a prevalence rate of 50% for thyroid nodules 1, 2 . Fine needle aspiration cytology (FNAC) of the thyroid gland is over 50 years old and is the single most important method of establishing a diagnosis in both adults and children. Recent guidelines published by the British Thyroid Association/Royal College of Physicians and the American Association of Clinical Endocrinologists (AACE)/Association Medici Endocrinologi(AME) emphasize that FNAC should be considered as the early investigation of choice for thyroid nodules and specifically for thyroid cancer 4,5 FNAC requires careful aspiration technique and meticulous interpretation of the findings by a skilled cytologist. Studies have suggested a sensitivity and specificity for predicting thyroid malignancies averaging 83% and 92% respectively 5, 6 . Unfortunately, FNAC can miss malignancies with a false negative rate of approximately 5% . Current guidelines recommend the usage of ultrasound guided FNAC (US FNAC) to reduce this error 1,5 .Studies have shown that US FNAC significantly reduces the number of inadequate fine needle aspirates and improves the diagnostic yield for malignancies 1,10 US FNAC also improves the yield of cancer found at surgery 11 The aim of our study was to investigate the role and accuracy of ultrasound guided fine needle aspiration cytology in the management of patients with thyroid nodules.
PATIENTS AND METHODS
Two hundred and eighty two FNACs of thyroid nodules were carried out at Mahatma Gandhi Medical College and Research Institute and the results reviewed. Out of this, 44 patients had US FNAC for assessment of thyroid nodules followed by thyroidectomy. A retrospective analysis of the data was carried out that included patient demographics, US FNAC results and the final histopathological reports. All patients had baseline thyroid function tests followed by ultrasound examination and guided FNAC of the thyroid nodules. A high resolution 7.5 MHz probe was used to guide a 23/25 gauge needle attached to a syringe to obtain cellular aspirates from the lesions. Cytological diagnosis was correlated with histopathology and the accuracy of ultrasound guided FNAC
Study parameters:
Demographic data
Sensitivity, specificity
Positive and negative predictive values
Diagnostic accuracy rate
Inadequate sample category
RESULTS
Data regarding 44 patients who had undergone US FNAC of the thyroid nodules followed by thyroidectomy was retrospectively analyzed. There were 3 men and 41 women in the study group, with age ranging from 18 to 51 years. The mean age was 39.6 years with male to female ratio of 1:13.7(Table 1). 29(63.6%) patients had non neoplastic lesions (nodular/colloid goiter, thyroiditis) and 14(31.8%) had neoplastic lesions on cytological examination. Overall, US FNAC yielded satisfactory cell samples in 42(95.4%) patients and inadequate material in 2(4.6%) patients (Table 2). An aspirate was considered adequate by the presence of 5 to 6 clusters of cells with each cluster containing 10 or more cells. Nodular goiter constituted the majority (55.2%) in the non neoplastic category and papillary carcinoma was the commonest (61.5%) cytological diagnosis in the neoplastic group as shown in Tables 3 and 4. On comparing the US FNAC reports of the 29 non neoplastic nodules with the final histological diagnosis, it was observed that 26 patients had same cytological diagnosis, 1 had papillary carcinoma (false negative) and 2 had Hashimoto’s thyroiditis (Table 5). The US FNAC results for the 13 neoplastic lesions were compared with the corresponding histological diagnoses. 8 patients had papillary carcinoma confirmed by histological study and out of 4 cases of follicular neoplasm, 2 were confirmed as follicular adenoma and 1 each of colloid goiter (false positive) and follicular carcinoma. One patient diagnosed as Hurthle cell neoplasm by US FNAC turned out to be Hashimoto’s thyroiditis on final histological study (false positive), Table 6. The sensitivity and specificity of US FNAC for diagnosing neoplastic lesions were 91.7% and 93.3% respectively. The diagnostic accuracy was 92.8%, positive predictive value (PPV) was 86.5% and negative predictive value (NPV) 96.5% (Table 7 and Table 8).
DISCUSSION
FNAC is considered as the gold standard in the evaluation of thyroid nodules. Major problems associated with free hand FNAC are significant false negatives (missed neoplasms) and difficulties in accurate identification of follicular lesions leading to wrong FNAC diagnoses 12 . Possible reasons cited for this include the technique of aspiration, smear preparation and experience of the cytopathologist. The AACE/AME has suggested that ultrasound should be employed routinely to detect features suspicious of malignancy in thyroid nodules and to identify lesions that would be suitable for FNAC . Ultrasound (US) is useful to guide the needle for fine needle aspiration of a thyroid nodule; it improves the quality of diagnosis in pre operative assessment of thyroid nodules and to appropriately select patients for thyroidectomy. Ultrasound guidance allows continuous visualization of the needle during insertion and sampling, which results in pinpoint accuracy with a high evel of safety. Some of the potential advantages of US FNAC in the evaluation of nodular thyroid disease are selecting the suspicious nodule for biopsy in a multinodular goiter and guiding the needle to take samples from nonpalpable nodules. A recent review of studies that evaluated the role of US FNAC in the detection of thyroid cancer revealed a sensitivity of 76%–98%, specificity of 71%–100%, false negative rate of 0%–5%, false positive rate of 0–5.7%, and overall accuracy of 69%–97% 13 23 . Another report based on a systematic review of 12 studies had shown a median sensitivity and specificity of 88% and 90.5% 24 . A large prospective cohort study had reported a marked increase in the diagnostic accuracy of FNAC from 85% to 95% when FNAC was combined with US guidance 25 . Our results have shown a sensitivity and specificity of US FNAC for diagnosing neoplastic lesions as 91.7% and 93.3% respectively. The false negative rate was 2.3%, PPV 86.5%, NPV 96.5% and the diagnostic accuracy was 92.8%. The accuracy of FNAC depends crucially on the technique, operator performing the aspiration and the cytopathologist analyzing it. Even under optimal conditions, the false negative rate for thyroid neoplasms can vary from 1% to 6% due to wrong diagnosis or sampling errors . Danese et al in their study have observed the false negative rate much lower for US FNAC when compared with free hand FNAC 27 . In our analysis, there was one patient who had cytological picture of nodular goiter whereas the histological study showed a small focus of papillary carcinoma in a background of multinodular goiter(false negative 2.3%). The majority of thyroid FNAC is now performed under US guidance and this has become mandatory at some of the centers. The major benefit of this technique is accurate sampling of small or multiple nodules 28 30 . Certain sonologic features of thyroid lesions are predictive of malignancy and hence such lesions can be accurately biopsied 31 . Another crucial benefit of using US FNAC is significant reduction in the number of inadequate aspirates 32 . Case series have reported rates of inadequate samples in the order of 15 30% for free hand FNAC. Many published studies have shown US FNAC to decrease the rate of inadequate samples from 15% to 3% when compared to free hand FNAC 17,33,34 . In a recent study, the authors have noted a prevalence rate of 8.5% for thyroid cancer in patients with inadequate samples and they recommended repeat aspirations by US FNAC technique 35 . It is possible that reduced number of inadequate aspirates may potentially lead to increase in the yield of cancer and the diagnostic accuracy of FNAC. The rate of inadequate specimens in our retrospective study was 4.5 % (2 out of 44 samples), which is comparable to the above quoted studies.
CONCLUSION
In conclusion, US FNAC greatly facilitates the precise and adequate sampling of tissues from thyroid lesions thus enabling the cytopathologist to make an accurate diagnosis. This may lead to the elimination of the cost and potential morbidity of unnecessary thyroidectomy.
Ultrasound guidance helps in the selection of the most suspicious focus within the nodule especially with a background of multinodularity. It is therefore desirable that practice guidelines recommend universal use of ultrasound guided FNAC for all nodular thyroid lesions, especially for inadequate smears from free hand FNAC, for small or nonpalpable nodules and multinodular goiters. US FNAC is the most accurate and cost effective method for diagnostic evaluation of thyroid nodules.
ACKNOWLEDGEMENTS
Authors acknowledge the immense help received from the scholars whose articles are citied and included in references of this manuscript. The authors are also grateful to authors/ editors/publishers of all those articles, journals and books from where the literature for this article has been review and discussed. Authors are grateful to IJCRR editorial board members and IJCRR team of reviewers who have helped to bring quality to this manuscript. The authors also thank all the residents and staff in the Department of Surgery, Departments of Pathology and Radiology, Dean and Vice Chancellor of Mahatma Gandhi Medical College & Research Institute for their support.
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5. Cobin RH, Gharib H, Bergman DA, Clark OH, Cooper DS, Daniels GH, et al. AACE/AAES medical/surgical guidelines for clinical practice: management of thyroid carcinoma. American Association of Clinical Endocrinologists. American College of Endocrinology. Endocr Pract. 2001; 7:202– 20.
6. Gharib H. Fine needle aspiration biopsy of thyroid nodules: Advantages, limitations, and effect. Mayo Clin Proc. 1994; 69:44–9.
7. Castro MR, Gharib H. Thyroid fine needle aspiration biopsy: Progress, practice, and pitfalls. Endocr Pract. 2003; 9:128–36.
8. Gharib H, Goellner JR. Fine needle aspiration biopsy of thyroid nodules. Endocr Pract. 1995;1:410–17.
9. Jeffrey PB, Miller TR. Fine needle aspiration cytology of the thyroid. Pathology (Phila) 1996;4:319–35.
10. Ahmet Selcuk Can and Kamil Peker. Comparison of palpation versus ultrasound guided fine needle aspiration biopsies in the evaluation of thyroid nodules. BMC Research Notes 2008; 1:12
11. Dilip K Sankhala, Samir S Hussein, Haddia Bererhi, Omeima El Shafie, Nicholas J Woodhouse, V Nirmala. Are scintigraphy and Ultrasonography necessary before fine needle aspiration cytology for thyroid nodules? Squ journal for scientific research Medical sciences 2001; 1: 29 33.
12. Kopald KH, Layfield LJ, Mohrmann R, Foshaq LJ, Giuliano AE. Clarifying the role of fine needle aspiration cytologic evaluation and frozen section examination in the operative management of thyroid cancer. Arch Surg 1989;124:1201–5.
13. Wu HH, Jones JN, Osman J. Fine needle aspiration cytology of the thyroid: ten years experience in a community teaching hospital. Diagn Cytopathol 2006;34:93–96.
14. Serna de la Saravia C, Cuellar F, Saravio Day E, Harach HR. Accuracy of aspiration cytology in thyroid cancer: a study in 1 institution. Acta Cytol 2006;50:384–387.
15. Sangalli G, Serio G, Zampatti C, Bellotti M, Lomuscio G. Fine needle aspiration cytology of the thyroid: a comparison of 5469 cytological and final histological diagnoses. Cytopathology 2006;17: 245–250.
16. Sahin M, Sengul A, Berki Z, Tutuncu NB, uvener ND. Ultrasound guided fine needle aspiration biopsy and ultrasonographic features of infracenti metric nodules in patients with nodular goiter: correlation with pathological findings. Endocr Pathol 2006;17:67–74.
17. Cai XJ, Valiyaparambath N, Nixon P, Waghorn A, Giles T, Helliwell T. Ultrasound guided fine needle aspiration cytology in the diagnosis and manage ment of thyroid nodules. Cytopathology 2006;17: 251–256.
18. Zagorianakou P, Malamou Mitsi V, Zagorianakou N, Stefanou D, Tsatsoulis A, Agnantis NJ. The role of fine needle aspiration biopsy in the management of patients with thyroid nodules. In Vivo 2005;19: 605–609.
19. Sclabas GM, Staerkel GA, Shapiro SE, et al. Fine needle aspiration of the thyroid and correlation with histopathology in a contemporary series of 240 patients. Am J Surg 2003;186:702–709; dis cussion 709– 710.
20. Ogawa Y, Kato Y, Ikeda K, et al. The value of ultrasound guided fine needle aspiration cytology for thyroid nodules: an assessment of its diagnostic potential and pitfalls. Surg Today 2001;31:97–101.
21. Mittendorf EA, Tamarkin SW, McHenry CR. The results of ultrasound guided fine needle aspiration biopsy for evaluation of nodular thyroid disease. Surgery 2002;132:648–653; discussion 653–654.
22. Kessler A, Gavriel H, Zahav S, et al. Accuracy and consistency of fine needle aspiration biopsy in the diagnosis and management of solitary thyroid nod ules. Isr Med Assoc J 2005;7:371–373.
23. Blanco Carrera C, Garcia Diaz JD, Maqueda Villaizan E, Martinez Onsurbe P, Pelaez Torres N, Saavedra Vallejo P. Diagnostic efficacy of fine needle aspiration biopsy in patients with thyroid nodular disease: analysis of 510 cases [in Spanish]. Rev Clin Esp 2005; 205:374–378.
24. Belfiore A, La Rosa GL. Fine needle aspiration biopsy of the thyroid. Endocrinol Metab Clin North Am 2001;30:361–400.
25. Koike E, Yamashita H, Noguchi S, Murakami T, Ohshima A, Maruta J, et al. Effect of combining ultrasonography and ultrasound guided fine needle aspiration biopsy findings for the diagnosis of thyroid nodules. Eur J Surg2001;167:656 1.
26. Mazzaferri EL. Management of a solitary thyroid nodule. N Engl J Med 1993;328:553 9.
27. Danese D, Sciacchitano S, Farsetti A, Andreoli M, Pontecorvi A. Diagnostic accuracy of conventional versus sonography guided fine needle aspiration biopsy of thyroid nodules. Thyroid 1998;8:15–21.
28. Cai XJ, Valiyaparambath N, Nixon Pet al. Ultrasound guided fine needle aspiration cytology in the diagnosis and management of thyroid nodules. Cytopathology 2006;17:251–6.
29. Robinson IA, Cozens NJA. Does a joint ultrasound guided cytology clinic optimize the cytological evaluation of head and neck masses?. Clin Radiol 1999;54:312–6.
30. Kojic Katovic S, Halbauer M, Tomic Brzac H. Importance of FNAC in the detection of tumours within multinodular goiter of the thyroid. Cytopathology 2004;15:206–11.
31. Kovacevic O, Skurla MS. Sonographic diagnosis of thyroid nodules: correlation with the results of sonographically guided fine needle aspiration biopsy. J Clin Ultrasound 2007;35:63–7.
32. Cesur M, Corapcioglu D, Bulut S, et al. Comparison of palpation guided fine needle aspiration biopsy to ultrasound guided fine needle aspiration biopsy in the evaluation of thyroid nodules. Thyroid 2006; 16:555–61.
33. Baskin HJ. Ultrasound guided fine needle aspiration biopsy of thyroid nodules and multinodular goiters. Endocr Pract 2004; 10:242 5.
34. Izquierdo R, Arekat MR, Knudson PE, Kartun KF, Khurana K, Kort K, Numann PJ: Comparison of palpation guided versus ultra sound guided fine needle aspiration biopsies of thyroid nodules in an outpatient endocrinology practice. Endocr Pract 2006; 12:609 14.
35. Orija IB, Pineyro M, Biscotti C, Reddy SS, Hamrahian AH: Value of repeating a non diagnostic thyroid fine needle aspiration biopsy. Endocr Pract 2007; 13:735 42.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524152EnglishN2013January26HealthcareAN EPIDEMIOLOGIC STUDY OF AWARENESS AND ATTITUDE ABOUT HIV/AIDS AMONG LONG DISTANCE TRUCK DRIVERS
English101104Ravi A. BhoviEnglish Santosh M. BiradarEnglishBackground: Long- distance truck drivers to ease their loneliness often engage in high risk sexual behavior by having unsafe sex with fellow crew members or visiting commercial sex workers (CSW). Objectives: To study the awareness and attitude about HIV / AIDS among long distance truck drivers. Methodology: 440 long distance truck drivers parking their vehicles at dhabas near National Highway passing through Bijapur were interviewed. Data was collected using pretested questionnaire. Analysis was done using proportions and percentages. Results: Overall knowledge of the truck drivers about mode of spread of HIV/AIDS is good. 7% of the respondents did not know the role of mother to child transmission. Some of the respondents had the misconception that AIDS can be contacted by mosquito bite (20.90%) and kissing (33.63%). 76% of the respondents were exposed to CSWs and their practice of using condoms was not found to be satisfactory. Half of the respondents have positive attitude towards HIV/AIDS patients. Conclusion: The knowledge about HIV/AIDS is good among the respondents. Their exposure to CSWs is high but use of condoms is not satisfactory. They have average attitude towards the HIV/AIDS patient. There is a need promote safe sex and consistent condom use. IEC activities need to be strengthened for creating better awareness and attitude towards HIV/AIDS infection.
EnglishCondom , HIV/AIDS, Truck drivers, Unsafe Sexhttp://ijcrr.com/abstract.php?article_id=1440http://ijcrr.com/article_html.php?did=1440Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524152EnglishN2013January26HealthcarePROTEIN ENERGY MALNUTRITION AND ITS ASSOCIATION WITH IMMUNIZATION STATUS AND COMMON MORBIDITIES AMONG 1-5 YEAR AGED CHILDREN IN SOUTHERN PART OF INDIA, MYSORE
English105110Santosh Kumar A.English Sunil Kumar D.English N.C. AshokEnglish Ragavendraswamy KoppadEnglishBackground: Protein Energy Malnutrition (PEM) is widely prevalent form of malnutrition among under five children and is still the major problem in our country especially in urban slums. Objectives: 1) To estimate the prevalence of PEM in children aged 1 to 5 years. 2) To study the association of immunization status and common morbidities on PEM of children aged 1 to 5 years Methods: A cross sectional study of 600 children of 1-5 year age group in urban slums of Mysore city was carried out with cluster random sampling method. The data was collected using a predesigned and pretested proforma. Clinical examination and anthropometry was used to assess nutritional status. WHO child growth standards, 2006 reference data were used to classify malnutrition. Results: Among 600 children examined, 285 (47.5%) were males and 315 (52.5%) were females. 560 (93.3%) had received primary immunization, while 40 (6.7%) children were partially immunized.Diarrhoea and ARI werereported in 222 (36.9%) and 83(13.8%) of children respectively during the past one month. The prevalence of underweight, stunting and wasting was 129 (21.5%), 135 (22.5%) and 9 (7.5%) respectivelyPrevalence of PEM was found to be higher in children who were partially immunized and was statistically significant. Among the children with history of ARI 64 (77.1%) were found to be underweight, 57 (38.7%) were stunted and 24 (58.9%) were wasted and was statistically significantly (p < 0.05). Underweight, stunting and wasting were seen in 119 (53.6%), 120 (54.1%) and 38 (17.1%) children respectively among children with history of diarrhoea and it was statistically significant. Conclusion: Immunization status and common avoidable morbidities like Acute respiratory tract infection and diarrhea plays an important role in nutritional status of the child.
EnglishPEM, Immunization status, common morbiditieshttp://ijcrr.com/abstract.php?article_id=1441http://ijcrr.com/article_html.php?did=1441Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524152EnglishN2013January26HealthcareCOMPARATIVE EVALUATION OF SHEAR BOND STRENGTHS OF ZIRCONIA CORE AND VENEER WITH LITHIUM DISILICATE CORE AND VENEER - AN INVITRO STUDY
English111117Shukoor UmerEnglish Hariharan AnnapoorniEnglish Abby AbrahamEnglish Plato PalathingalEnglishThe purpose of the study was to compare the shear bond strengths of Zirconia core and veneer with Lithium Disilicate core and veneer. In the study 20 all ceramic bilayered specimens were fabricated and divided into two test groups containing 10 specimens each. Materials used were Zirconia samples and Lithium Disilicate samples. Nominally identical bar shaped core (Cercon and Lithium Disilicate) specimens of 5.0 mm length, 5.4 mm width and 13.0 mm height were produced following Schmitz-Schulmeyer method. After a thin layer was fired, veneering ceramic was built up to final dimensions (4.0 mm length, 5.4 mm width, 3.0 mm height) using a metal mold according to Schmitz-Schulmeyer method. Load was applied parallel to the long axis of the specimen through a wedge in an instron universal testing machine at the core-veneer interface at a crosshead speed of 5 mm/min until delamination of the veneering ceramic occurred. The results of the study demonstrated Zirconia having better bond strength compared to Lithium disilicate.
EnglishShear bond strength, Schmitz-Schulmeyer method, Delamination, Thermocycling.http://ijcrr.com/abstract.php?article_id=1442http://ijcrr.com/article_html.php?did=1442Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524152EnglishN2013January26HealthcareCOMPARATIVE STUDY OF PULMONARY FUNCTION TESTS ON DIFFERENT TRIMESTERS OF PREGNANCY
English118122Sushma JadhavEnglish V.B. DudhamalEnglish S.S. KaradkhedkarEnglish Sayeeda AfrozEnglish N.A. RazviEnglishThe Pulmonary function tests were carried out in 70 normal pregnant women attending Antenatal clinic at government medical college Nanded. Out of 70 pregnant women, 16 were of first trimester, 22 were of second trimester and 32 were of third trimester. The aim of the study was to see whether any changes occur in pulmonary function tests in the 3 trimesters of pregnancy.The pregnant ladies were from age group of 16 to 30 years. Their weight and height were recorded. Using computerized med spiror instrument, following paramesters were studied i.e. FVC, FEV 1% FEV3, PEFR and MVV were recorded. 30 non pregnant women of same age group were taken as control group. The readings were compared of first and second trimester, second and third trimester and first and second trimester. Following observations were noted. PEFR was found to be significantly decreased in first trimester while other readings were not significantly decreased in first trimester as compared to second and third trimester. All the parameters also compared with control group. It showed that there was decline in all the values compared to control values, which was highly significant.
EnglishTrimester PEFR, FEV 1%, FEV 3%, FVC, MVVINTRODUCTION
The pulmonary function tests were carried out in different trimesters of pregnancy, on 70 normal pregnant women attending antenatal clinic at Govt. Medical College, Nanded. Out of 70 pregnant women, 16 were of first trimester, 22 were of second trimester and 32 were of third trimester. 30 non pregnant women of same age group were taken as control group. The aim of the study was to see whether any changes occur in pulmonary function test in the 3rd trimesters of pregnancy as compared with that of control group. The pregnant ladies were from age group of 16 to 30 years. Their weight and height were recorded. Using computerized med spiror instrument, following parameters were studied i.e. FVC, FEV1, FEV3, PEFR and MVV were recorded.
METHODS
The study was conducted on 70 normal pregnant women attending antenatal clinic at Govt. Medical College Nanded,by prior permission of institutional Ethical committee. The pulmonary function tests were carried out in 1st, 2nd & 3rd trimesters of pregnancy. Age group of pregnant ladies were from 16 to30 yrs. Control group of 30 nonpregnant women of same age group & belonging to same socio-economic status were taken. The anthropometric measurements like height (cm), weight (kg) were recorded. The subjects were made to sit comfortably on a chair and were asked to breathe through mouthpiece of computerized medspiror instruments, with nose clip. All the procedures were carried out in respiratory laboratory during morning hours between 8am to 12pm in quite laboratory set up in order to alleviate the emotional and psychological stress. During the test subject was adequately encouraged to perform at their optimum level. Test was repeated at least three times and the best matching results were considered for analysis. All the recordings were done at the BTPS.
RESULTS
The results showed that mean height (152+3.5 cms), weight (49+5.8kg) of the subject were considerably lower than the western standards. All the subjects were coming from periphery of Nanded district which is considered as a tribal area. It was the cause of lower height and weight. Four respiratory parameters FVC (forced vital capacity %), FEV1 (forced expiratory volume in first second), FEV3 (forced expiratory volume is third second) MVV (maximum ventilator volume) and PEFR (peak expiratory flow rate) were determined. Table 1 showed that all the parameters were compared with control group. It showed that there was decline in all the values compared to control values, which was highly significant. Table 2 showed that all the parameters were compared between first and second trimesters, second and third trimesters, first and third trimesters. The parameters compared between first and second showed that decline in values in first trimester as compared to second trimester which was not significant. Only that PEFR shows significant decline values. The parameters compared between second and third trimester showed that only PEFR and MVV decreases from second to third trimester. The parameters compared between first and third trimester showed that there was decline in all parameters from first to third trimesters
DISCUSSION
Four respiratory parameters PVC, FEV1, FEV3, MVV and PEFR were determined in both 70 pregnant women and control group of 30 non pregnant women of same age group. Our results shows highly significant decline in FVC, FEV1, FEV3, MVV and PEFR in all trimesters, of pregnancy as compared to control group. Similar results have been reported by other coworkers. The above declining in the first trimester can be attributed to morning sickness , lack of nutrition and to lodging of trophoblast cells in the alveoli from the maternal uterine sinuses [1], whereas in second and third trimester it may be due to mechanical pressure of enlarging gravid uterus. Elevating the diaphragm and restricting movements of lungs [1] [2] and thus hampening forceful expiration, it may be also due to brochoconstrictor effect of decrease alveolar pco2 on the bronchial smooth muscles. PEFR was found to be significantly decreased in first trimester as compared to second and third trimester. According to reference [3] PEFR is more sensitive to muscular element in respiration and as anemia produces muscle weakness, it reflects in lowering the PEFR. In the first trimester there was anemia due to more sickness and lack of supplementation of iron and calcium as compared to second and third trimester in which the subject were taking the iron and calcium supplementation.[4] FEV1 & FEV1/FVC% were significantly lower in third trimester pregnant women than that of non- pregnant & FEV1/FVC% gradually decrease from 1st to 3rd trimester of pregnant women.(5) FEV1 ,FVC decrease in pregnant group which is a restrictive condition & not obstructive.PEFR decrease states that it might caused by upward displacement of diaphragm, reduced strength of expiratory muscles & mechanical effects of growing uterus. Other factors as morning weakness, lack of motivation & resistance to exertion contribute in decrease MVV.(6) The study showed significant decrease in all as compared to nonpregnant group.(7)
CONCLUSION
Comparative study of pulmonary function tests on different trimesters of pregnancy showed that respiratory parameters like PEFR significantly compromised due to mechanical pressure of gravid uterus, diaphragm restricting the movement of lungs especially in third trimester of pregnancy. There was decrease in respiratory parameters from first to third trimesters of pregnancy due to poor nutrition because all the subjects coming from middle class and poor socio-economic status. Poor nutrition may cause decrease in functions of respiratory muscles. To establish the cause of decrease in respiratory parameters, further studies are to be undertaken by hormonal assay in different trimesters to know effect of increase of hormones on respiratory parameters.
Englishhttp://ijcrr.com/abstract.php?article_id=1443http://ijcrr.com/article_html.php?did=14431. Pandy MR. Nishith SD, Bhatt RV, pulmonary functions in pregnancy.J obstel Gynac India 1972;22;1-3.
2. Puranic BM, Kurhade GA, Kaore SWB, Patwardhan SA, Kher Jr. PEFR in pregnancy –A Longitudinal study. Indian J physiol pharmacol 1995; 39 (2)(135-139).
3. Singhal V, Saxena K Effect of anemia on respiratory and metabolic during 3rd trimester of pregnancy. Indian J physiol pharmacol 1987; 3[2]; 130-135.
4. Knuttgen HG, Emerson K, physiological response to pregnancy at rest and during exercise. J. Appl. Physiol. 1974; 36;549.
5. Monga U, kumari K. pulmonary function in Punjabi pregnant women. Indian J physiol pharmacol 2000; 44 (1); 115-116.
6. Dr Lata Gupta. Evaluation of PFT in normal pregnant (2nd and 3rd trimester) and non pregnant women.
7. John Pramod- effect of advanced gestation on cellular activity in respiratory systems in females.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524152EnglishN2013January26HealthcareTUBULO-VILLOUS ADENOMA OF FIRST PART OF DUODENUM-AN UNUSUAL PRESENTATION
English123126Vishwas JohriEnglish Syed Javed ArshiEnglishTubulo-villous tumours of the duodenum are rare tumours which account for less than 1% of duodenal neoplasms, 88% of which are located in the second part of duodenum. The remaining 12% are equally distributed in first and third part of the duodenum [1, 2]. A high rate of malignant transformation complicates management with surgical treatment options ranging from wide local excision to radical pancreaticoduodenectomy [1]. A case of duodenal villous adenoma of the first part of duodenum presenting with vague generalized abdominal pain, nausea and weight loss is reported because of its rarity.
EnglishTubulo-Villous adenoma, duodenal tumourINTRODUCTION
Neoplastic growth in the small intestine is relatively uncommon. Its incidence is usually one-tenth that of a similar lesion of the colon. According to prospective endoscopic studies on elevated lesions of the duodenum, the incidence of duodenal adenoma in all patients referred to diagnostic endoscopy was only 0.4% [3] Tubulovillous adenomas of the duodenum are rare tumours comprising less than 1% of duodenal neoplasms [1,3]. The widespread use of upper gastrointestinal endoscopy has resulted in more frequent reporting of patients with duodenal adenomas. The clinical presentation is variable, with duodenal obstruction a late feature of large tumours. The coexistence of malignancy, in 21% to 53% of tumors [1, 4] complicates surgical management. Various surgical procedures, ranging from simple local excision to radical pancreatic duodenectomy are done depending on the case per se [5].
Case Report
A 35-year old female presented with a 6-month history of vague abdominal pain, nausea, sour eructation and decreased appetite. Abdominal pain was diffuse in nature and spread all over the abdomen. The pain was mild to moderate in nature; simultaneously patient also developed sensation of nausea though it never leads to an episode of vomiting. She also had loss of appetite. She received treatment for acid peptic disease (APD), without any relief for 4 months. There was no history of dysphagia, heart burn, blood in stools or alteration of bowel habits. Her routine clinical examination was unremarkable. Her blood counts, urine and stool examination was normal. The stool was negative for occult blood. She was HIV negative. Abdominal sonography was normal. Upper GI endoscopy showed a polypoid mass in the first part of duodenum (Fig.1). Subsequently CT scan of abdomen was done. It revealed well defined round nonenhancing isodense filling defect measuring 17 × 18 ×14 mm on the medial aspect of the first part of duodenum. No other lesion was noted in any of the bowel loops. Lower GI endoscopy was normal. A provisional diagnosis of solitary duodenal polyp was made. The patient was taken up for laparotomy. Intraoperative a soft mass was felt in first part of duodenum. Duodenotomy was done, a papillomatous mass was found, it was excised enbloc from the base. Then Heineke-Mikulicz pyloroplasty was done. Histopathologic examination revealed a polypoid tumour with numerous branching villi (Fig.2). These were lined by long columnar epithelium with nuclei showing stratification at places. . Underlying lamina propria showed hyperplastic Brunner’s glands (Fig.3) and slight mucosal inflammation. There was no pathologic evidence of H pylori infection in stomach and duodenum. The tubulo-villous glands were positive for PAS. It was diagnosed as tubulo-villous adenoma of first part of duodenum. The patient did well postoperatively and was discharged on 10th postoperative day. The patient has been followed up by doing upper GI endoscopy at 6 monthly intervals to look for any recurrence. The patient remains disease free after 4 years.
DISCUSSION
Villous tumor of the duodenum (VTD) was first described by Perry in 1893 as a broad-based cauliflower-like mass that he referred to as a duodenal papilloma. These lesions are relatively uncommon with only 73 cases reported by Komorowski and Cohen in a 1981 review [5, 6]. Pathologic descriptions have included the terms villous adenoma, villous papilloma, papillary adenoma, tubulovillous adenoma, and villoglandular polyp [5]. The male: female ratio was 1:1, with a mean patient age of 60 years (range: 29-81 years) [2]. Duodenal villous adenomas tend to be large lesions. In a previous review, 22 of 23 villous adenomas were greater than 3 cm in diameter. As small VTD can easily be missed by barium swallow examinations, today the most useful and accurate diagnostic tool is probably fiberoptic endoscopy with full visualization of the duodenum which enables both visual identification and biopsy of the tumour. The other methods that can be used in diagnosis and staging are ERCP, USG, CT and endoscopic USG [7]. 88% of the adenomas are found in the second portion of the duodenum while remaining 12% are equally distributed in first and third part of duodenum [2]. The most frequent presenting symptoms are jaundice, weight loss, epigastric pain, melena or guaiac+ stool, partial intestinal obstruction or may remain asymptomatic. Other less frequent symptoms include diarrhoea, anaemia, fatigue, fever (secondary to cholangitis from biliary obstruction), and recurrent episodes of pancreatitis. The high incidence of malignancy in villous lesions of the duodenum as well as the frequent involvement of the ampulla of Vater has resulted in considerable controversy regarding proper management. A 21-53% rate of cancer in villous adenomas of the duodenum has been reported in duodenal villous adenomas and much less in tubulo villous and tubular adenomas [1, 4, 7]. VTD may occur in most of the patients with Gardner’s syndrome and FAP. Polyps in the duodenum occur in 40-91% of FAP patients, and are true dysplastic lesions at risk of cancer. Peri ampullary carcinoma is now the leading cause of death after proctocolectomy in patients with FAP which is affecting up to 12% of patients. For these reasons patients with FAP should have routine Upper GI endoscopy [7]. Based on this data our patient was evaluated and no FAP was found. We concur with the opinion of others who have recommended that all villous adenomas of the duodenum be considered potentially malignant until proven otherwise. Depending on the localization, extension of tumour endoscopic snare excision or ablation, local submucosal excision, full thickness excision, pancreas sparing duodenectomy and pancreaticoduodenectomy (PD) is recommended. Complete excision is mandatory though opinions differ as to the best method of resection.
CONCLUSION
Tubulo-villous adenomas of the duodenum are rare tumours comprising less than 1% of duodenal neoplasms. But with widespread and increased availability of upper gastrointestinal endoscopy their incidence is bound to increase. In our opinion, endoscopically obtained tissue biopsy should guide the management protocol in the adenomas of the first part of duodenum as the distance from papilla of vater endows them with a wider margin of safety. If malignant transformation has not taken place yet, then complete local excision followed by biannual endoscopic examination to rule out recurrence remains the best approach as it preserves the functional integrity. Even in selected cases with dysplasia or carcinoma in situ complete local excision may be tried before resorting to a radical procedure like pancreaticoduodenectomy.
ACKNOWLEDGEMENT
Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed. Conflict of interest The authors report no conflict of interest.
Englishhttp://ijcrr.com/abstract.php?article_id=1444http://ijcrr.com/article_html.php?did=14441. Michael E.C. Mcfarlane. Villous tumour of the duodenum: report of a case and review of the literature. J hepatobiliary pancreat surg (2001) 8:107–109.
2. Galandiuk S, Hermann RE, Jagelman DG, Fazio VW, Sivak MV. Villous tumors of the duodenum. Ann surg 1988; 207: 234-9.
3. Ji Hoon Kim, Jung Woo Choi, Yeon Seok Seo, Beom Jae Lee, Jong Eun Yeon, Jae Seon Kim et al. Inverted cystic tubulovillous adenoma involving Brunner’s glands of duodenum. World J Gastroenterol 2007 June 21; 13(23): 3262-3264
4. Dupont-Lampert V, Landmann J.Tubulovillous adenoma of the duodenum: case report and review of the literature. Schweiz Med Wochenschr. 1989 Jul 29;119(30):1057- 9
5. Charles W. Chappuis, M.D., Frank C. Divincenti, M.D. and Isidore Cohn, jr., M.D. villous tumours of the duodenum. Annals of surgery; 207:1989: 593-598.
6. Perry EC. Papilloma of the duodenum. Trans Pathol Soc (London) 1893; 44:84-88.
7. Sabahattin Aslan, Bahadir Çetin, Fatma Markoç, Abdullah Çetin. A duodenal villous adenoma associated with in situ carcinoma: A case report. Turkish Journal of Cancer 2001; 31(4):162-167.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524152EnglishN2013January26HealthcareSTUDY OF PROGNOSTIC SIGNIFICANCE OF SERUM C-REACTIVE PROTEIN AND ESR IN ACUTE ISCHEMIC STROKE
English127134Krishna Murthy H.A.English Renuka Prasad Y.S.EnglishBackground of the study: The stroke is defined as rapidly developing clinical signs of focal or global disturbance of cerebral function, lasting more than 24 hrs or leading to death, with no apparent cause other than vascular origin.1,2 An increasing body of evidence has linked inflammation with the pathogenesis of atherothrombotic stroke. The serum C-reactive protein (CRP) and ESR are acute-phase reactants, are indicators of underlying inflammation of endothelium and novel plasma markers for atherothrombotic disease.3,4,5
Aims and objectives: 1. To study the serum concentration of C-Reactive Protein [CRP] and ESR in patients of Acute ischemic stroke. 2. To compare it with that of age and sex matched controls. 3. One month follow up of the cases to know the results of stroke.
Methods: It is a case control study, in this 50 cases, who has CT brain confirmed, first attack of Acute ischemic stroke and 50 healthy controls were taken. For all patients CRP and ESR levels were measured, with in 72 hours of onset of stroke and followed up for one month to know the results of cases.
Results: The mean serum CRP level among the cases was 4.5±2.58mg/L and that among the controls it was 0.88±0.41 mg/L with the p value of < 0.001. There were 88% (44) of cases and 24% (12) of controls has CRP levels >0.8mg/L and 12%(6) of cases and 76%(38) of controls has CRP levels EnglishAcute ischemic stroke, CRP, ESR.INTRODUCTION
The WHO defined, stroke as “rapidly developing clinical signs of focal or global disturbance of cerebral function, lasting more than 24 hrs or leading to death, with no apparent cause other than vascular origin”. The stroke manifests by various neurological signs and symptoms depends on the area, extent of involvement and the underlying causes. These include hemiplegia, monoplegia, cranial nerve palsy, sensory impairment, paraplegia and speech disturbances etc. Of these, about 90% of patients have hemiplegia as the most common presentation. 1,2 The many studies have shown that, the inflammation has a significant role with the pathogenesis of atherosclerotic stroke. The inflammation may induce atherosclerosis by increasing the serum levels of cytokines, fibrinogen, clotting factors, and leukocytes by altering the functions of endothelial cells.The serum C-reactive protein (CRP) and ESR are acute-phase reactants, are markers of underlying systemic inflammation and novel plasma indicators for atherosclerosis. Some clinical trials have shown, an association between high concentration of serum C-Reactive Protein [CRP], ESR and ischemic strokes.3,4,5 Not many studies are available on rise in serum CRP and ESR levels in acute ischemic stroke. It was therefore, planned to study serum CRP and ESR levels in acute ischemic stroke, and to compare these levels with those obtained in healthy controls.
C-Reactive protein
C-reactive protein was discovered by Tillet and Francis in 19306 . Inflammation is an important feature of atheroma and is associated with activation and proliferation of macrophages, endothelial cells and smooth muscle cells7 . The serum CRP and ESR are the earliest acute phase reactants to increase during the inflammatory response. Today, however, the best single test of acute inflammation is a serum CRP level that can be readily quantified by nephelometry.8 The median circulating concentrations of C - reactive protein is 0.8 mg/L. Normal range may be as low as 0.07 mg/L and among apparently healthy individuals 90% have less than 3 mg/L .9 The rate of CRP synthesis and secretion increases within hours of an acute injury or the onset of inflammation10, probably under the influence of humoral mediators such as leucocyte endogenous mediator (endogenous pyrogen) 11 and prostaglandin PGE. The serum CRP concentration may reach peak levels as much as 300mg/ml within 24-48 hours12. The Edward T.H. Yeh, MD showed that both statins and finofibrates can inhibit CRP induced MCP-1 induction.13
The Erythrocyte Sedimentation Rate (ESR);14,15
ESR is a simple and inexpensive laboratory test for assessing the inflammatory or acute response.The ESR was also an independent predictor of short-term stroke outcome. An ESR > 28mm/hr was associated with a poorer prognosis.
Aims and objectives
1. To study the serum C - reactive protein [CRP] level and ESR in patients of acute ischemic stroke.
2. To compare it with that of age and sex matched controls
3. One month follow up of cases to know the results.
MATERIALS AND METHODS
Source of data:
Patients with clinical and CT Brain diagnosed first ischemic stroke admitted to VICTORIA and BOWRING AND LADY CURZON Hospitals, BMC ,Bangalore were studied with equal number of age and sex matched healthy volunteers as controls with one month of followup for cases.
Method of collection of data
Study Design: The study is the case control study in which cases and controls were selected by considering of inclusion and exclusion criteria. Detailed history was taken, clinical examination was done as per proforma and the necessary investigations were done for both cases and controls.
Inclusion Criteria:
All patients of clinical and CT scan brain confirmed first ischemic stroke admitted within 72hrs of symptom onset and healthy age and sex matched volunteers who are relatives of the patient.
Acute infectious disease
All patients of stable or unstable angina, acute myocardial infarction.
Immunological disorders.
Known or suspected neoplastic disorders
Recent [less than 3 months] major trauma, surgery, burns
Osteoarthrosis, costochondritis, rheumatoid arthritis, ankylosing spondylitis.
Sample Size:
50 cases were studied with equal number of controls.
Protocol of the study:For every case and control selected, clinical data and results of routine investigations were prospectively recorded.In both cases and controls, blood for CRP and ESR was taken by performing venipuncture and estimation was done in Clinical Microbiology Laboratory, BMC, Bangalore with the follow up of patients for one month to know the condition and results.
Procedure: The serum C - reactive protein and ESR estimation.
Principle: The serum CRP is a rapid slide agglutination procedure for the direct detection and semiquantitation of C-reactive protein. The reagent, a latex particle suspension coated with specific antihuman C- reactive protein antibodies, agglutinates in the presence of CRP in patients serum.8,16,17,18
Positive Results: The presence of agglutination indicates content of CRP in the sample equal to or greater than 0.8mg/L.
Negative Results: Homogenous suspension of fluid (lack of agglutination) indicates a CRP level lower than 0.8mg/L. The detection limit of this test is 0.8 mg/L. therefore, values of less than 0.8 mg/L were taken as normal concentration of CRP. Values of more than 0.8 mg/L were taken as elevated CRP.16,17,19 .
ESR Level Estimation; 20
METHOD; The International Committee for Standardization in Hematology (ICSH) recommends the use of the Westergren method. Normal values are 15 mm/hr or less for men and 20 mm/hr or less for women.20 The ethical clearance was taken from Bangalore Medical College Ethical Commitee,Bangalore. The written consent from all the participants was taken after explaining in their own language about the study , methods used on them and risks involved.
RESULTS AND OBSERVATIONS
In this study majority of cases were in the age group of 42-70years constituting 58% of cases. In the control group majority were in the age group of 41-60 years, constituting 64%. The mean age for cases and controls were 55.60±14.68years and 51.50±8.36 years respectively. In the present study the most common mode of presentation of CVA was hemiplegia in 88% followed by cranial nerve palsy [VII] in 44%, aphasia in 36% and altered sensorium in 28%. Headache was present in 56% of cases. Seizure was a symptom in 38% of cases along with other complaints (table1). In the present study of 50cases and equal number of controls, the risk factors seen are smoking, constituting [50% Vs.28%], hypertension [ 46% vs. 20%], diabetesmellitus [27%Vs.16%], Familyhistory [59%Vs.44%], Mixeddiet [85%Vs.84%] among cases and controls respectively(graph1). TIA was present in 27% of cases only. The mean CRP level in the present study is 4.5±2.58mg/L among the cases and 0.88±0.41mg/L among the controls respectively, which is statistically significant with the p value of 0.8mg/L was present in 88% compared to controls who had 0.8mg/L in 24% respectively (table3). In this study ESR was raised in 90% of cases and 44% of controls, with the mean value of 32.33±11.80mm/hr and 19.80±6.80mm/hr respectively (table4). In 50% (23) cases CRP level was more than 0.8mg/l with in 24hours of onset of Stroke.In16.66% of cases between 24 to 48 hours and in 33.33% of cases between 48 to 72hours, the serum CRP level was raised above the normal level.But time of Stroke was not statistically associated with elevated CRP levels (table5). After one month of follow up 12%(6) of cases with CRP value of 5.4mg/L and ESR of 38mm/hr were died, the 26%(13) of patients with CRP value of 3.2mg/L and ESR of 25mm/hr were recovered from neurological features and 62%(31) patients with CRP value of 4.9mg/L and ESR of 34mm/hr were remained with same neurological features, which was statistically significant with the p value of 0.8mg/l. In the study done by Dhamija R K et al, 25 the 77.7% of cases and 12.54% of controls has CRP>0.6mg/L (table6). By these observations we can be sure that inflammation is an important risk factor of endothelial damage. The mean ESR level among the cases and controls in the present study is 32.33±11.80mm /hr and19.80±6.80mm/hr respectively.Which was comared with the study done by Agarwal et al24 ,where the values were 33.92mm /hr and 14.08mm /hr among the cases and controls respectively (table7). In follow up of for one month,the 12% cases with serum CRP value of 5.4mg/L and ESR of 38mm/hr were died and 62% patients with serum CRP value of 4.9mg/L and ESR of 34mm/hr were remained with same neurological features.The death was seen in highly raised serum CRP and ESR cases. Again this proves that, the inflammation is an imporatant risk factor of endothelial damage. A study done by Muir et al. had shown that CRP levels within the first 72 hours after an acute ischemic stroke are an independent marker for predicting survival26 . Our study had shown that the third day CRP levels of patients who died within the first 30 days were significantly higher than the surviving patients. It has been proved that a large cortical infarcts patients have a higher CRP values than normal at the time of presentation and the prognosis is worse in patients with increased CRP levels. 3 Our study shows that patients who could walk independently at the end of the study duration have the lowest CRP value. The increased CRP levels in patients who died and the lowest CRP levels in the walking group may be an indicator of the level of underlying inflammation. By our study and other new literature suggests that CRP and ESR are prognostic markers of atherosclerosis.
CONCLUSION
The serum CRP and ESR levels were higher in the cases compared to controls and the statistically significant results were also seen with the follow up of the cases.Hence it can be concluded that, inflammation is an important risk factor of endothelial damage and atherosclerosis. So measures to reduce the inflammation of endothelium and atherosclerotic plaque of blood vessels, in the long run can significantly reduce the incidence of stroke and its consequences in predisposed individuals.
ACKNOWLEDGEMENT
Authors acknowledge the great help received from the scholars, whose articles cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed. Authors are grateful to IJCRR editorial board members and IJCRR team of reviewers who have helped to bring quality to this manuscript.
Englishhttp://ijcrr.com/abstract.php?article_id=1445http://ijcrr.com/article_html.php?did=14451. WHO, Technical Report Series 1976:469.
2. Aho K, Harmsen P, Hatano S, et al. Cerebrovascular disease in the community: results of a WHO collaborative study. Bull World Health Organ 1980; 58(1): 113-130
3. Natalia S .Roast, Philip A Wolf, Carlos S, Kase et al,’’Plasma concentration of Creactive protein and risk of ischemic stroke and trancient ischemic attack’’. The Framingham Study. Stroke Nov 2001;32;2575-2579
4. Guo Y, Jiang X, Zhou Z, Chen S, Zhao H, Li F ‘’Relationship between levels of serum creactive protein,leucocyte count and carotid plaque in patients with ischemic stroke’’ JHuazhong Univ Sci Technolog Med Sci . 2003;23[3];263-5.
5. Di Napoli M, Papa F, Bocola V. “Prognostic Influence of increased CRP and fibrinogen levels in ischemic stroke”. Stroke 2001;32:133-138;917-924
. 6. Tillet WS, Francis T, “Serological reactions in peneumonia with a non protein somatic fraction of pneumococcus”, J Exp Med., 1930;52;561-571.
7. Paul M Ridker, MD; Peter W.F. Wilson, MD; Scott M. Grundy, MD.”Should C-Reactive Protein be added to metabolic syndrome and to Assessment of Global Cardiovascular Risk?”. Criculation 2004;109:2818-2825
8. David F Keren, Jeffrey S. Warren. “Diagnostic immunology” 1992; 57-58.
9. Pepys MB, “The acute phase response and Creactive protein”, Chapter 11, 13.3 in Oxford Text book of Medicine, 3rd Edition, Weathurall DJ, Ledingham JGG, Warrell DA, Tokyo: Oxford University Press, 1906; 1527-1533.
10. Kushner I, Feld Man G, “Control of acute phase response Demonstration of C-reactive protein sysnthesis and secretion by hepatocytes during acute inflammation in the rabbit”, J. Exp Med, 1978, 148;466-77.
11. Merriman CR, Pulliam LA, Kampschmidt RF, “Effect of leukocytic endogenous mediator on C-reactive protein in rabbits” Proc Soc Exp Bio Med 1975;149;782-84.
12. Wade S. Smith, Stephen L. Hauser, Donald Easton. Cerebrovascular diseases. Harrison’s principles of internal medicine.16th edition. (Eds). Dennis L. Casper, Anthony L. Fauci, Dan L. Longo, Eugene Braunwald, Stephen L. Hauser. McGraw-Hill 2004.
13. Edward T.H. Yeh, MD. “CRP as a Mediator of Disease”. Circulation 2004; 109(Suppl II):II-11-II-14.
14. Sox HC, Liang MH: The erythrocyte sedimentation rate. Ann Intern Med 1986; 4:515-523
15. A.Chamorro, Md; N. vila, Md; Early prediction of stroke severity, role of the erythrocyte sedimentation rate. STROKE. 1995;26:573-576.
16. Shine B, De Beer FC, Pepys MB, “Solid phase radioimmuno assays for CReactive protein”, Clin CHem Acta 1981;117;13-23.
17. Oliveria EB, GOtschlich EC, Liu T, “Comparative studies on the binding properties of human and rabbit C-reactive protein”, J Immunol 1980;124;1396-402.
18. Tsujimoto M, Inoue K, Mojima S, “Creactive proteininduced agglutination of lipid suspensions prepared in the presence and absence of phosphatidlyl choline”, J. Biochem 1980;87;1531-37.
19. S C Mahapatra,PK Pillai,PK Hui,SK Tripathy, BK Behera,KK Samal “C-Reactive proteins in Thrombotic stroke” JAPI. Vol50;Dec2002
20. International Council for Standardization in Haematology (Expert Panel on Blood Rheology): ICSH recommendations for measurement of erythrocyte sedimentation rate. J Clin Pathol 1993; 46:198-208
21. Bernard Rosner (2000), Fundamentals of Biostatistics, 5th Edition, Duxbury.
22. M. Venkataswamy Reddy (2002), Statistics for Mental Health Care Research, NIMHANS publication, INDIA
23. J.David Curb, Robert D Abbott, Beatriz L Rodriguez et al ‘’CRP and the future risk of Thrombo embolic stroke in healthy men.’’Circulation April 2003,22,107[15].
24. Agarwal MP, Singh NR, Kaur IR. “CReactive Protein in acute cerebralinfarction”.JAPI. Vol51;Dec 2003
25. Dhamija RK, Gaba P, Jais M, Kumar M, Sherwal BL ‘’A Study of C-Reactive Protein levels in patients of Acute Ischemic Stroke and its correlation with lipids’’ JAPI.Vol51,Dec2003.
26. Muir KW, Weir CJ, Alwan W, Squire IB, Lees KR. C-reactive protein and outcome after ischemic stroke. Stroke. 1999;30(5):981–985.
List of abbreviations used; CRP-Creactiveprotein; ESR-Erythrocyte sedimentation rate.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524152EnglishN2013January26HealthcareEVALUATION OF ANTIOXIDANT LEVEL AND TRACE METALS IN ANEMIA
English135139Naila MasoodEnglish Imran Ali ShaikhEnglish Ali Raza MemonEnglish Saira BalochEnglishBackground: Anemia is a disorder characterized by reduction in hemoglobin concentration of blood
below the normal level.
It is a global problem, mainly affecting poor people in developing countries.
Methods: to determine trace metals fifty intravenous blood samples anemic patients and normal
subjects were collected and immediately centrifuged to obtain the supernatant liquid, serum of both the
groups for analysis.
Results: The mean serum levels of magnesium, zinc, copper, and iron and
antioxidant activity in anemic patients were 16.05±1.14ppm, 4.33±0.28 ppm, 2.5±0.2ppm,
1.50±0.28ppm and 1.27±0.05ppm respectively. Serum magnesium, zinc, iron and antioxidant levels
were significantly lower whereas, the higher level of Copper was observed in anemic patients
compared to the controls.
Conclusion: Supplementation with deficient trace elements may reduce the
severity of symptoms and complications associated with anemia.
EnglishAnemia, Iron, Zinc, Copper, Magnesium, Antioxidant Activity.INTRODUCTION
Anemia is one of the world’s most prevalent health problems, especially among adult and pregnant females approximately 35% to 75% (56% on average) are anemic in developing countries (1). “The World Health Organization has identified that iron and folic acid deficiency is a severe problem in Pakistan and it has devastating impacts on health and survival. It has been estimated that iron deficiency leads to 22,000 maternal deaths for the last 10 years (2). There are various other nutritional and communicable causes of anemia, iron (Fe) deficiency is often a causative aspect in many of these cases (3). Fe deficiency anemia leads to weakness (4), poor physical growth (5), and delayed psychomotor development (6). A recent study on the prevalence and etiology of nutritional anemia in urban areas of Hyderabad, Pakistan indicated a high prevalence of anemia and Fe deficiency in 60% of adults (7). Zinc (Zn) deficiency in humans has been found in infants, schoolchildren and adults (8). Zinc deficiency associates with Fe deficiency anemia in areas where Fe deficiency is a problem (9). It was investigated that anemia is one, of the major manifestations of copper (Cu) deficiency both in animals and human beings (10). It is essential to maintain Fe homeostasis in the human body; its deficiency leads to anemia and neutropenia (11). Cuassisted enzymes are necessary for the utilization of Fe to make hemoglobin, a main component of red blood cells (11). Recent attention has been directed to the element chromium (Cr); it can improve insulin sensitivity and therefore may be involved in carbohydrate and lipid metabolism (12). The determination of trace quantities of metals in biological samples requires the use of sensitive and selective techniques such as atomic absorption spectrometry. In this study, we evaluate whether Fe, Cu, Mg and Zn deficiency is related to increased level of toxic metals in blood samples of anemic and controls of both gender with age range 16– 50 years. The samples were prepared method. Fe, Cu, Mg and Zn concentrations in samples under study were evaluate by atomic absorption spectrometer, while antioxidant activity was analyzed by spectrophotometer. In this study, we aimed to evaluate the levels of Cu, Mg, Zn, and Fe and antioxidant activity in serum of anemic patients.
MATERIAL AND METHODS
This investigation has been conducted among three medical units of Liaquat University of Medical and Health Sciences (LUMHS) Jamshoro. The group of patients were been selected within the age range of 16-50years of both gender. The metals copper, iron, magnesium, and zinc in the blood serum were determined by Atomic Absorption Spectrometry (AAS) (Model, A-20 Varian). Whereas anti oxidative activity was measured as a ratio of Fe (II)/Fe (III) present in the blood serum. Iron (II) was determined spectrophotometrically as Fe (II)- TPTZ (2, 4, 6-tris (2-pyridyl)-s-triazine) colored complex formed at pH 4-5 and measured at 595nm wavelength. Whereas, for the determination of total iron, iron (III) was first reduced to Fe++ using vitamin C as reducing agent and then complexed with TPTZ .The complex so produces is directly proportional to the concentration of Fe (II) produced and Fe (II) already present i.e. total iron in the blood sample in presence of antioxidant. The difference of the total iron and the iron (II) present in the serum is the measure of iron (III). Trace metals were determined using air-acetylene flame. The standards from 1 to 5 ppm for each of the metal separately were run on the spectrometer and the calibration curves were obtained prior to run the samples for the determination of metals in the blood serum of normal subjects and the malarial patients. Blood samples were collected from 50 healthy controls in fasting conditions and a similar condition was maintained while taking blood samples of anemic patients. Each blood sample was centrifuged at 5000 rpm for 20 minutes. The supernatant blood serum was used for the analysis of metals copper, iron, magnesium, and zinc using Atomic Absorption Spectrometer inserting appropriate hollow cathode lamp in it. All standards used were of analytical grade.
Chemicals and reagents
Sulphosalicylic acid was obtained from Merck, Damstadt, Germany and other chemicals to prepare standards were purchased from Sigma Chemical Co. All chemicals were of analytical grade.
Stock Solutions and working
Metal standards Stock solution of 1000 ppm Cu, Fe, Mg, and Zn for each were prepared for corresponding sulphate salts of analytical grade (Sigma Chem.). Working standards were prepared from the stock solutions by diluting with appropriate volume of deionized water and addition of few drops of corresponding concentrated acid.
Statistical Analysis
All statistical analyses were performed using computer program Excel X State (Microsoft Corp., Redmond, WA) Student’s t test was used to assess the significance. Results are expressed as mean ± SD.
RESULTS AND DISCUSSION
Table 1 shows the blood serum levels of trace metal and antioxidant levels in anemic patients with compare to control subjects. The results show significant increase in serum copper levels, where as serum iron, magnesium, zinc and antioxidant levels were decreased in anemic patients compared to the controls.
The Table 1 show the levels of trace metals (Fe,Cu, Mg and Zn) and antioxidant activity evaluated in blood samples of anemic patients as compared to controls. Fe deficiency is probably the most common nutritional disorder in the world. Presently estimate based on the WHO criteria specify that around 600–700 million people worldwide have a marked Fe deficiency anemia and about half the adults in developing countries are affected (13). The data of the trace metals under study in blood samples of control and anemic patients are shown in Table 1 and Figure 1(a) to 3(a). The results are given as mean values with standard deviation (±SD) for each metal and antioxidant activity. The mean values of iron in the anemic patients were significantly lower compared to healthy controls (Fig: 1(b). The results indicate the prevalence of Fe deficiency anemia in both genders. In the population of developing countries, the amount of Fe absorbed from the diet is not sufficient to meet many individuals’ requirements. The consumption of a predominantly cereal-based diet, rich in phytate, oxalate, phosphate, fiber, and other inhibitors of Fe absorption, was the main cause of Fe deficiency diseases. Phytates strongly inhibit Fe absorption in a dosedependent fashion, and even small amounts of phytates have a marked effect (14). If the amount of absorbable Fe in the diet cannot be immediately improved, Fe supplement must be included in the diet to control Fe deficiency anemia (15). The concentrations of Zn in anemic patients were found to be significantly lower compared to healthy controls (Fig: 2(a). Zn deficiency may be a contributing factor in anemia (16). Zn deficiency in developing countries is due to low consumption of meat and fish along with food rich in phytate. Food rich in phytate significantly reduce the absorption of Zn, increasing the chance of Zn deficiency. The higher level of Cu was observed in anemic patients as compared to the healthy controls (Fig: 2(b) Copper is required for normal infant development, red and white blood cell maturation, Fe transport, bone strength, cholesterol metabolism, myocardial contractility, glucose metabolism, brain development, and immune function (17). A deficiency of either Fe or Cu will result in anemia, namely, Fe deficiency anemia or Cu deficiency anemia. Copper is essential for the functioning of many Cu-dependent enzymes (18) such as ceruloplasmin (responsible for antioxidant protection, Fe metabolism, and Cu transport), and it was established that the anemia appears to be related to defects in Fe mobilization due to the combined defect of both red ceruloplasmin ferroxidase activity and intracellular utilization (19). Cu is a major component of catalytic centers of different redox enzymes, and thus, its presence is essential for normal physiologic function such as cellular respiration, free radical defense, synthesis of melanin pigment, connective tissue biosynthesis, and cellular Fe metabolism (20). About 95% of the Cu in the blood is bound to ceruloplasmin. These enzymes play a role in the regulation of Fe metabolism. The mean values of magnesium in the anemic patients were significantly lower compared to healthy controls (Fig: 1(a). Low serum magnesium causes potassium, calcium and neuromuscular disturbances, central nervous system and cardiovascular alterations, like arrhythmias (21). Also it can alter glucose homeostasis, increase atherosclerosis, hypertension, myocardial infarction, osteoporosis, migraine, asthma, chronic fatigue syndrome, among others (21, 22). More research on the effects of magnesium deficiency on the health of people is needed to warrant interventions to prevent it. The mean values of Anti-oxidant activity in the anemic patients were significantly lower compared to healthy controls (Fig: 3(a). Antioxidant activity which shows decreasing tendency in patients and this parameter could be used as a biomarker for obtains the status of these patients under medical therapy and its affectivity.
CONCLUSION
It suggests that use of magnesium as a supplementary diet and use antioxidant activity as the status of drug response to greater number of patients. The decreased levels of iron and zinc can be maintained by given supplement of these metals as therapy.
Englishhttp://ijcrr.com/abstract.php?article_id=1446http://ijcrr.com/article_html.php?did=14461. Hall A, Miguel E (2001) Anemia in schoolchildren in eight countries in Africa and Asia. Public Health Nutr 4(3):749–756.
2. ADB to pilot project to combat nutritional problems Pakistan. [Online]. 2006 Mar 26[2007 April 5]. Available fr om : htt p://www.adb.org/ Media /Articl/2006/9538. Pakistan-flourfortification/default.asp.
3. Lanzkowsky P (1995) Pediatric hematology and oncology, 2nd edn. Churchill Livingstone, New York.
4. Haas JD, Brownlie TT (2001) Iron deficiency and reduced work capacity: a critical review of the research to determine a causal relationship. J Nutr 131:676S–688S.
5. Grantham-McGregor S, Ani C (2001) A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr 131:649S–666S.
6. Sherriff A, Emond A, Bell JC, Golding J (2001) Should infants be screened for anaemia? A prospective study investigating the relation between haemoglobin at 8, 12, and 18 months and development at 18 months. Arch Dis Child 84:480–485.
7. Afridi HI, Kazi TG, Kazi GH (2005) Evaluation of status of trace and toxic metals in scalp hair samples of normal and anemic human subjects. American Biot Lab 23(8):27.
8. Castillo-Duran C, Garcia H, Venegas P (1994) Zinc supplementation increases growth velocity of male children and adolescents with short stature. Acta Paediatr 83:833.
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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524152EnglishN2013January26General SciencesCLIMATE CHANGE IMPACT: THE NEED OF ECO-EARTH STEWARDSHIP IN INDIA
English2727V. SivakumarEnglishBalanced ecosystem is very important for sustainance of life on earth. In this short communication, author has highlighted on importance of eco system and climate change impact.
Englishhttp://ijcrr.com/abstract.php?article_id=1486http://ijcrr.com/article_html.php?did=1486