Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411020EnglishN2018October26HealthcareVEGF in Renal Cell Carcinoma -  A Mini Review English0105Deepika ChandrasekaranEnglish Sandhya SundaramEnglish Kadhiresan N.English Padmavathi R.EnglishAngiogenesis is a very important process in the progression of the tumor growth. Vascular endothelial growth factor (VEGF) is a key factor in angiogenesis. The main function is vascular permeability, angiogenesis and endothelial cell growth. An inactivated or impaired tumor suppressor gene Von Hipple Lindaue(VHL) causes accumulation of hypoxia inducible factor (HIF-1A) and leads to increased production of VEGF. The more the expression of VEGF, the worse is the survival and recurrence in many malignancies like Renal Cell Carcinoma. VEGF-targeted therapy plays a major role in various carcinomas involving VEGF pathway for their cancerous growth.  English Angiogenesis, VEGF, CarcinomaIntroduction: Cancer is rapidly becoming a major cause of death both in developed and developing nations(1). Kidney cancers are high in western population and low in eastern countries. But recent studies have found the increasing incidence of renal tumors in Asian countries(2) Among the various adult tumors, 3% of the tumors occur in the kidney of which common is the renal cell carcinoma about 90%. The incidence rate is about 2,00,000/year worldwide(2). The estimated incidence of RCC in India among males is about 2/100,000 population and among females is about 1/100,000 population(3). Etiology includes both internal factors like genetic involvement (mutations), poor immune status and external environmental factors like food habits, pollution, industrialization etc(4). Renal cell carcinoma (RCC) is a heterogenous type of tumor showing variation in histological features, clinical multiplicity and unpredictable behavior. RCC having high mortality-incidence ratio constitutes 2-3% of adult malignancies(5) It is common in men than women, often in the elderly age group. Surgical treatment is effective only in tumors localized to the kidney (5,6). Initial treatment is radical or partial nephrectomy, which is a most successful intervention. When the cancer is limited to the renal parenchyma, the 5 year survival rate is about 60-70%. Renal cell carcinoma being resistant to radiation and chemotherapy, responds targeted therapy in some cases(6). This helps to shrink the tumor to half of its size. Malignant tumors grow due to abnormal cell signaling, proliferation, apoptosis inhibition, and supporting angiogenesis (7,8). Molecular targeting plays a potential role in treatment as it helps in designing new anti angiogenic remedies. It is therefore of therapeutic significance to define the VEGF expression(9). Activation of an oncogene or inactivation of a tumor suppressor gene is essential to bring about a genetic alteration in RCC. The tumor suppressor gene VHL inactivation leads to accumulation of hypoxia inducible factor (10). This induces the mRNA transcription of growth factor and produces anti-apoptotic signaling which leads to angiogenesis. Angiogenesis: Angiogenesis is the process of new capillary formation. They are the outgrowths of endothelial cells from the already existing vessels. The early event in tumorigenesis is the onset of angiogenesis (11). This facilitates tumor growth and metastasis. Folkman and coworkers demonstrated that the tumors can grow up to 1.75mm when the required nutrition is available. But growth beyond this size requires additional new blood vessels. Angiogenesis is brought about by hypoxia or increased angiogenic stimulators(12). It is essential for the modification of tumor from dormant state to malignant state. Tumor development occurs by two important steps such as tumor avascular phase and tumor vascular phase. During the avascular phase, the tumor remains localized whereas in vascular phase, metastasis begins (12,13). Then new capillaries begin to grow, extending their supply throughout the tumor and it grows rapidly. The important step in this process is the vascular endothelial growth factor(VEGF). It helps in secretion of proteases, migration and proliferation. It is an independent prognostic tumor marker. Cancers expressing VEGF grow and metastatise at a faster rate(14). Vascular Endothelial Growth Factor: It is a disulfide bonded dimeric glycoprotein. Its molecular mass is 34-46 kDa. Its main role is stimulating vascular permeability and proliferation of the endothelial cell. During the Embryonic stage VEGF helps in endothelial cell differentiation, migration and maturation of the nephron. In the adult stage VEGF plays an important role in vascular permeability, regulation of glomerular permeability, maintaining basement membrane composition, podocyte survival and mediates endothelium dependant vasodilatation (14). VEGF is the key mediator of angiogenesis in cancer. The main function is vascular permeability, angiogenesis and endothelial cell growth. The four members in the VEGF family areVEGF-A VEGF-B VEGF-C VEGF-D. All members of the family perform important functions both in normal and tumor conditions (15). VEGF-A: The prototype member of this family is VEGF–A. Its main function is anigiogenesis. VEGF-A is a potential factor in the growth of endothelial cells. VEGF-A is located on the chromosome 6p23.1. Using the reverse transcription polymerase chain reaction, various isoforms of VEGF identified are VEGF 121, VEGF 165 VEGF 189 and VEGF 206. VEGF–A plays an important role in binding with the receptors. It is mainly present in lungs, kidneys and heart. Molecular mass is 34-45 kDa(14,15). VEGF-B: VEGF-B is located on the chromosome 11q3.3. It is the second member in VEGF family. Its isoforms are VEGF B167 and VEGF B 186. Its main function is embryogenic angiogenesis. It is expressed in cardiac and skeletal muscles. Molecular mass is 21-30 kDa(14,15). VEGF-C: VEGF-C is located on the chromosome 4q34.3. It has multiple isoforms like VEGF C62, VEGF C129 and VEGF C184. VEGF C62 plays major role in kinase phosphorylation and cell adhesion in epithelial cells of the proximal tubule. It mainly takes part in lymphangiogenesis. It is expressed in breast cancer, gastric and colon cancer. VEGF B and C are less expressed in RCC. Molecular mass is 20-21kDa(14,15). VEGF –D: VEGF-D is located on chromosome Xp22.31.VEGF-D is synthesized as an immature protein. It has N and C terminal propeptides which are absent in other VEGF family members. It is expressed in lung, heart, muscle and colon. Molecular mass is 20-21kDa(14,15). VEGF receptors: The VEGF family members act by binding with receptors. There are three important receptors. They are VEGFR-1, VEGFR-2 and VEGFR-3. 30 exons are involved in coding of these receptors. Exon 1 encodes the secretary region and exon 2-15encode the extracellular region. The exon 16 encodes the Transmembrane- spanning polypeptide and exons 17-30 encode the tyrosine kinase. All different types of VEGF bind with different receptors and exert their response at cellular level. VEGFR 1 and VEGFR 2 play major role in angiogenesis whereas VEGFR3helps in lymphogenesis. VEGF A binds with VEGFR1 and 2, and is highly expressed in RCC. VEGFR 3 binds with VEGF C and D. It is mainly found in the lymphatic endothelial cells (15,16). VEGF and the Kidney: VEGF is expressed in the glomerular podocytes and tubular epithelial cells present in the proximal, distal and collecting ducts. VEGF receptors are localized in the mesangium, glomerular and peritubular capillaries. By double label immune histochemistry, VEGF receptor proteins were identified in the endothelial cells of preglomerular, glomerular and post glomerular vessels in the adult (17). An inactivated or impaired tumor suppressor gene (VHL) causes accumulation of hypoxia inducible factor (HIF-1A) and leads to production of VEGF(18). The more the expression of VEGF the worse is the survival and recurrence in many malignancies like RCC. VHL gene inactivation in most of clear cell RCC tumors (approximately 60%) leading to VEGF overexpression promotes tumor angiogenesis, development and growth. Molecular mechanism of VEGF action: VEGF A is the important member of the family. It binds to VEGFR 1 and VEGFR2. VEGFR2 appears to mediate almost all of the cellular responses to VEGF. The three important domains of the receptor are: seven extracellular immunoglobulin Ig domains, a single transmembrane region and an intracellular tyrosine kinase (TK) domain. The VEGF family members initiate cellular responses by binding to these tyrosine kinase receptors present on the cell surface. Then they become activated through transphosphorylation(19). The phophorylation occurring in the receptor activates phosphoinositol 3 kinase (PI3K)/Akt and mitogen activated protein kinase(MAPK). PI3K/Akt signaling pathway mediates angiogenesis(19). The production of the secondary messenger phosphatidylinositol-3, 4, 5-triphosphate and the serine/threonine kinase(Akt) is catalyzed by PI3K. VEGFR1 binds to the p85 regulatory subunit of PI3K on Tyr1213 and 1333. This helps in controlling angiogenesis. Similarly VEGFR2 binds to p85 subunit of PI3K on Tyr799 and 1­­­­­173.Akt is activated by the products of phosphatidylinositol 3 phosphates kinase. Dysregulated Akt activity occurs in many tumors by tumor suppressor gene inactivation (19,20). Factors that alter functions of VEGF: VEGF is the important angiogenic factor. The VEGF pathway recognition and regulation is the important step in targeted approaches. The control of angiogenesis is a promising factor in the treatment of cancer. Activators of VEGF: Cigarette smoking: Smoking increases the RCC risk through chronic ­­­­tissue hypoxia and increased DNA damage due to sensitivity to tobacco carcinogens. Tobacco smoking is an important source of cadmium (nephrotoxic agent) exposure. An individual inhales 10% of cadmium through smoking(21). Cigarette smoking is the principal factor in cancer progression. Nicotine is the major chemical component responsible for addiction in tobacco products. All tobacco products contain carcinogenic substances like polycyclic hydrocarbons (PAH) and tobacco specific nitrosoamines(TSNA), which play a vital role in development of cancer. It causes carcinogenesis through initiation, promotion and progression. These factors stimulate endothelial cells to proliferate, migrate and enhance angiogenesis and metastasis (22). Hypoxia: The up-regulation of VEGF expression is stimulated by hypoxia. Thereby new blood vessels form and supply the deoxygenated area with the needed nutrition. Obesity: It is hypothesized to induce oxidative stress and chronic tissue hypoxia (23). Hypertension: It is hypothesized to include formation of reactive oxygen species and chronic renal hypoxia, thereby leading to HIF upregulation(24). Reactive oxygen species: VEGF stimulates Reactive oxygen species(ROS) production. VEGFR2-mediated signaling involves ROS followed by endothelial cell proliferation. Other factors include stress and environmental factors(25). RNA and protein microarray studies show the high expression of VEGF in all RCCs. This over expression increases the vascularity leading to tumor growth and poor survival. Blocking this factor results in regression of the tumor. VEGF also suppress antitumor immune responses by inhibiting dendritic cell activation. This supports the fact that VEGF blockade can enhance the immune response against the tumor. Based on this property, VEGF targeted therapy has become a promising treatment for RCC (26). Suppressor of VEGF: Several factors suppress the angiogenesis by inhibiting the VEGF pathway. The most promising anti-VEGF approach is antisense oligodeoxynucleotides (AS-ODN) (27). Suppression by AS-ODN was reported in many cancers. Anti-angiogenesis or angiogenesis inhibitor therapy: Many anti-angiogenesis agents were developed to target cell proliferation, growth and induce regression of the existing vessels. They were all developed to target the various malignant tumors and non-neoplastic conditions which benefit from anti VEGF therapy, suggesting the influence of VEGF as a pathophysiologic mechanism in the disease processes (27). Metastatic renal cell carcinoma is resistant to radio and chemotherapy. Immune mechanisms are found to be useful in regulating tumor growth.Interleukin-2 and IFN-alpha are the immunotherapeutic agents used.               The two main targeted therapies are the monoclonal antibody eg: bevacizumab (Avastin), and small-molecule tyrosine kinase inhibitor eg:sorafenib (BAY 43-9006). Mechanism of action of bevacizumab is found to be through the following processes such as microvasculature regression, angiogenic normalization and inhibition of new vessel formation (28). The continued use of bevacizumab can prevent the new vessel formation and thereby improving the duration of response, and delaying disease progression(29). The treatment with bevacizumab is beneficial but cause side effects like hypertension, gastrointestinal perforation etc. Targeting VEGF as a Therapeutic Strategy: The rationale for targeting VEGF is because of its action in tumor vascularisation. VEGF circulating in the blood acts on the endothelial cells. It need not penetrate tumor tissue to inhibit tumor vasculature through VEGF. Angiogenesis has limited importance in normal physiology like wound healing and female reproduction. Therefore inhibition of VEGF would not be expected to cause any side effects that can occur with other cancer treatments, particularly chemotherapy(29,30).It acts on endothelial cells, which are stable, dormant and have a long lifespan. This stability means the cells are less likely to mutate to a treatment-resistant phenotype making them a potential target for long-term therapy (30). Anti VEGF agents are currently used for malignant tumors like renal cell carcinoma, Rheumatoid arthritis and other inflammatory conditions and other non-neoplastic conditions. Conclusion: VEGF is found to play a major role in angiogenesis and maintenance of immature vessels. This coordination is lost in tumor tissues stimulated by VEGF, leading to prolific growth of disordered vessels. VEGF increases the permeability of blood vessels, resulting in poorly perfused tumors, followed by hypoxia stimulating further VEGF production. These effects make it difficult for chemotherapy to access to tumor tissue. Inhibition of VEGF results in normalization of permeability, improving ease of access for treatments such as chemotherapy. Hence the role of VEGF in tumor progression and whose inhibition leading to regularization is understood. Acknowledgement: This research was supported by the Indian Council of Medical Research – Talent Search Scheme and Sri Ramachandra Institute of Higher Education & Research (Deemed University). We acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. We thank the authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed. Conflicts of interest: nil Englishhttp://ijcrr.com/abstract.php?article_id=2534http://ijcrr.com/article_html.php?did=2534 GP Abraham, T Cherian, P Mahadevan, TS Avinash, D George, E Manuel, Detailed study of survival of patients with renal cell carcinoma in India. Indian journal of cancer. 2016, Volume:53, Issue:4,Page:572-574. Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics, 1999. CA Cancer J Clin 1999;49:8 31. Imran Ali, Waseem A. Wani and Kishwar Saleem, cancer scenario in India with future perspectives. Cancer therapy volume 8, November 1 2011,56-70. Ljungberg B, Campbell SC, Cho HY, et al. The epidemiology of renal cell carcinoma. EurUrol 2011;60:29-36. Borje Ljungberg, Nigel C Cowan, Damian C Hanbury, Milan Hora, Markus A Kuczyk, Axel S Merseburger et al, EAU Guidelines on RCC 2010 updates, European urology vol 58, july 12 2010,398-406 Herbert T. Cohen, McGovern FJ, Medical progress renal cell carcinoma, The New England journal of medicine vol 353, November 12 2005, 2477-2490. Allan J Pantuck, Ammon Zisman, Arie S Belldegrun, The changing natural history of renal cell carcinoma. Journal of urology. Vol 166, issue 5. Nov 2011, 1611 – 1623. David S. Finley , Allan J Pantuck, Arie S Belldegrun, Tumor biology and prognostic factors in renal cell carcinoma. The official journal of the society for translational oncology. Vol 16 supplements 2, Feb 2011, 4-13. Napoleone Ferrara, Role of vascular endothelial growth factors in regulation of angiogenesis. Kidney international vol 56, july 1999, 794-814.  Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 2003;3:721–732. Mehdi Rajabi and Shaker A. Mousa.The Role of Angiogenesis in Cancer Treatment Biomedicines. 2017 Jun; 5(2): 34. Mousa S.A., Davis P.J. Angiogenesis and anti-angiogenesis strategies in cancer. In: Mousa S.A., Davis P.J., editors. Anti-Angiogenesis Strategies in Cancer Therapies. 1st ed. Academic Press; Amsterdam, The Netherlands: 2016. Lamszus K., Ulbricht U., Matschke J., Brockmann M.A., Fillbrandt R., Westphal M. Levels of soluble vascular endothelial growth factor (VEGF) receptor 1 in astrocytic tumors and its relation to malignancy, vascularity, and VEGF-a. Clin. Cancer Res. 2003;9:1399–1405. J.Jacobsen K, Grankvist K, Rasmuson T, Bergh A, Landberg G, Ljungberg B, Expression of vascular endothelial growth factor protein in human renal cell carcinoma, B J U International 2004, vol 93, 297 – 302. Lawerence F. Brown, Berse B, Jackman RW, Tognazzi K, Manseau EJ, Dvorak HF, Senger DR, increased expression of vascular permeability factor and its receptors in kidney and baldder carcinoma. American journal of pathology vol 143, 5 November 1993, 1255-1263. McMahon G, VEGF receptor signaling in tumor angiogenesis. Oncologist. 2000;5 Suppl 1:3-10. Bieke FF. Schrijvers,  Flyvbjerg A, De Vriese AS., role of vascular endothelial growth factor in renal pathophysiology. Kidney international vol 65, 2004, 2003-2017 Kallio PJ, Pongratz I, Gradin K, McGuire J, Poellinger L. Activation of hypoxia-inducible factor 1α: posttranscriptional regulation and conformational change by recruitment of the Arnt transcription factor. Proc Natl Acad Sci USA. 1997;94:5667–5672.   Dai J., Peng L., Fan K., Wang H., Wei R., Ji G., Cai J., Lu B., Li B., Zhang D., et al. Osteopontin induces angiogenesis through activation of PI3K/AKT and ERK1/2 in endothelial cells. Oncogene. 2009;28:3412–3422. doi: 10.1038/onc.2009.189.  Karar J, Maity A. PI3K/AKT/mTOR Pathway in Angiogenesis. Front Mol Neurosci. 2011 Dec 2;4:51. Ejaz S, Lim CW. Toxicological overview of cigarette smoking on angiogenesis. Environ Toxicol Pharmacol. 2005 Sep;20(2):335-44. Hakuoh Konishi, Jenny Wu, John B Cooke, chronic exposure to nicotine impairs cholinergic angiogenesis. Vascular medicine vol 15, January 2009, 47-54. S. Miyazawa-Hoshimoto, elevated serum VEGF is associated with visceral fat accumulation in human obese subjects. Diabetologiavol 46, October 8, 2003, 1483-1488. Stojanovic M, Goldner B, Ivkovic D. Renal cell carcinoma and arterial hypertension. Clin Exp Nephrol. 2009 Aug;13(4):295-299. Karthigayan Shanmugasundaram and Karen Block, Renal Carcinogenesis, Tumor Heterogeneity, and Reactive Oxygen Species: Tactics Evolved Antioxid Redox Signal. 2016 Oct 20; 25(12): 685–701. T Kamba, DM McDonald, Mini review, Mechanism of adverse effects of anti-VEGF therapy for cancer, British Journal of Cancer 2007, vol 96, 1788-1795. T. Kamba, DM McDonald, Mechanism of adverse effects of anti VEGF therapy for cancer. British journal of cancer, vol 96, April 2007,1788-1795. Napoleone Ferrara, Bevacizumab, a humanized anti VEGF monoclonal antibody for cancer therapy. Biochemical and biophysical research communications, vol 333, June 2005,328-335. Brian I. Rini, Vascular Endothelial Growth Factor Targeted Therapy in Renal Cell Carcinoma: Current Status and Future Directions Clinical Cancer Res 2007; 13 (4) February 15, 2007. Gordana Djordjevic, Vladimir Mozetic, Danijela Vrdoljak Mozetic, VanjaLicul, Koviljka MatusanIlijas, Elvira Mustac, et al, Prognostic significance of vascular endothelial growth factor expression in clear cell renal cell carcinoma, Pathology – Research and Practice Vol 203 (2007)99–106. Nguyen Ba Phuoc, Hidetoshi Ehara, Takahiro Gotoh, Masahiro Nakano, Shingo Kamei,  Takashi Deguchi and Yoshinobu Hirose, Prognostic value of co-expression of carbonic anhydrase ix and vascular endothelial growth factor in patients with clear cell renal cell carcinoma, Oncology Reports 20: 525-530, 2008. Yousef H Aldebasi, Arshad H Rahmani, Amjad A Khan, and Salah Mesalhy Aly: The effect of vascular endothelial growth factor in the progression of bladder cancer and diabetic retinopathy. International Journal of Clinical Experiment Medicine 2013; 6(4): 239-251. Naoyuki Fujita, Takatsugu Okegawa, Yuichi Terado, Mitsuhiro Tambo, Eiji Higashihara, and Kikuo Nutahara,. Serum level and immunohistochemical expression of vascular endothelial growth factor for the prediction of postoperative recurrence in renal cell carcinoma, BMC Research Notes 2014, 7:369 Thomas Powlesa, Michael Staehlerb, Börje Ljungbergc, Karim Bensalahd, Steven E. Canfielde, Saeed Dabestanif, et al Updated EAU Guidelines for Clear Cell Renal Cancer Patients Who Fail VEGF Targeted Therapy, European Urology, Volume 69, Issue 1, January 2016, Pages 4-6

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411020EnglishN2018October26HealthcareAssessment of Nutritional Status of Teenage Adolescent Girls in Urban Slum of Varanasi   English0610Divya RaniEnglish Jitendra Kumar SinghEnglish Mona SrivastavaEnglish Pragya VermaEnglish Deepali SrivastavaEnglish S. P. SinghEnglishAim: India has one of the fastest growing youth populations in the world and adolescent girls of age 13 to 19 year constitute nearly to 66 million. Nutritional deficiencies have far reaching consequences, especially in adolescent girls. Adolescents are more vulnerable to malnutrition. 1. To assess the nutritional status of teenage adolescent girls and 2. To determine the association between socio demographic profile and nutritional status. Methodology: A cross sectional study   was carried out to assess the association between socio demographic profile and nutritional status of teen age adolescent girl in Varanasi city. A total no 418 teen age adolescents of 13 to 19 years were selected from urban slum of Varanasi during 2016. Results & Discussion: Nutritional status was assessed by anthropometric measurements. Result shows that 60.3% of adolescent girls were undernourished l 35.2% were normal and only 4.6% were overweight. Age and socio economic status of adolescent girls were significantly associated with their nutritional status (p < 0.05). Conclusion: It was found that higher proportions of adolescent girls were undernourished. This indicates that adolescents in urban slums need health awareness and importance of nutrition to maintain nutritional status.  EnglishMalnutrition, Adolescent, Nutritional statusIntroduction       Adolescence is the transitional period between childhood and adulthood. During this period individual move towards physical and psychological maturity, and economic independence and acquire their adult identity. According to World Health Organization, adolescent is the period of life spanning the ages between 10 to 19 years. [1] And it constitutes about 22.8 per cent of the population in India. [2] In general adolescent girls are the worst sufferers of the ravages of various forms of malnutrition because of their increased nutritional needs and low social power. [3]       Nutritional deficiencies have far reaching consequences, especially in adolescent girls. If their nutritional needs are not met, they are likely to give birth to undernourished children, thus transmitting under nutrition to future generation. Unfortunately assessment of nutritional status of adolescent girls has been the latest explored area of research particularly in India. [4] The urban slum adolescent girl is subjected to more physical and mental challenges on a day-to-day basis due to ever increasing pressure of modernization as compared to the rural set up. Malnutrition prevails in slum area due to low economic status, less awareness about healthy diet of adolescent girls. Hence it is essential to assess the nutritional status of adolescent girls, especially in slum area. Objectives: 1. To assess the nutritional status of teenage adolescent girls. 2. To determine the association between socio demographic profile and nutritional status. Material Methods: A community based cross-sectional study was carried out in slum areas of Varanasi, Uttar Pradesh on 418 adolescent girls aged between 13-19 years. Out of the 210 slums, five slums (Indrapur, Gilat Bajar, Bhogabeer chupepur karundi) were selected by use of stratified random sampling methods. Study participants (Teen age girls aged 13-19 years and unmarried) present in a family at the time of interview were included in the study. Girls suffering from severe illness and unable to communicate during interview were excluded from the study. Tools for data collection includes Performa for demographic characteristics i.e. age, religion, residence, type of family, education, occupation and per capita income, and anthropometric measurements (Height, Weight and Body Mass Index (BMI). This study was approved by Institute Ethical Committee, Institute of Medical Sciences, and Banaras Hindu University. Measurements: Height: Height was measured in centimeters that were marked on a wall with the help of measuring tape. All girls were measuring against the wall without footwear and with heels to getter and their heads positioned so that the live of vision was perpendicular to the body. A glass scale was brought down to the top most point on the head. [5] Weight: The weight was measured using a weighing machine (Libra) with an accuracy of +100 guess the subjects were asked to remove their footwear before measuring thin weight. The scales were recalibrated after each measurement. Accuracy of the weighing scale was verified from time to time against known weights. [6] BMI: BMI was calculated as weight in (kg) divided by height in (m2) and classified under standard criteria of Asian Criteria. Statistical Analysis: Data has been coded and was entered into the MS Excel. For the analysis of data Statistical Package of Social Science (SPSS 21.00 Version) was used. Percentage for all variables was calculated. Association between Nutritional status with independent variables was tested by applying Chi square test. P-value less than 0.05 were considered as statistical significant. Ethical clearance: The study protocol was approved by the Ethical Committee of Banaras Hindu University, India (Approval number: ECR/526.Inst/UP/2014 Dt.31.1.14). The study purpose and the procedure used for collecting information were clearly explained to each participant and they were all informed that they were free to leave the study at any time without prejudice. Written informed consent was obtained from all study participants. Privacy and confidentiality were maintained throughout and personal identifiers were removed prior to the data analysis. Out of 418 adolescent girls participated in the study, 48.3% belonged to 17-19 years of age group. Majority (96.7) of subjects was Hindu and almost half of them (48.3%) were from SC/ST category. More than three-fourth (78.7%) was from nuclear families and only 21.3% were from joint families. Table 2 represents the socio-economic characteristics of the study participants. Majority (96.9%) of the adolescent were literate and few (11.1%) were discontinued their education. In regard to education of fathers and mothers of study subjects, 21.8% and 39.2% were illiterate respectively. Occupational status of study subject shows, 13.9% adolescent girls were working outside (involve in service, business) and majority of 86.1% of the girls were students. In regard to occupation of fathers, 39.0% were in govt./pvt.Service, one fourth (25.1%) were lobour and 22.0% involved in business where as 4.6% involved in agriculture. Similarly, In regard to occupation of mothers, 76.1 %  were house wife and 12.4% were engaged in lobour work and few involved in business/service (9.1%). The maximum percentage (44%) of fathers was labourers, 22% had small businesses, and 10% were in the service sector. It was found that about 47% of the participants belong to upper lower class of socio-economic status followed by lower middle (25.8%), upper middle (14/8%) and upper class (11.5%). Regarding BMI, more than half (60.3%) were found to be under nourished,  among them 20.3% were in grade III, 15.1% in grade II & 24.9% in grade I under nutrition.  Around one third (35.2 %) were normal or well nourished, and overweight and pre- obese constitute only 3.6% and 1.0% respectively. Table 4 describes association between nutrition status and socio demographic variables of teen age girls in urban slum area. The nutritional status of study subjects were significantly associated with  age (pEnglishhttp://ijcrr.com/abstract.php?article_id=2535http://ijcrr.com/article_html.php?did=25351. Ghai O.P., Gupta P. & Paul Vk: Essential Paediatrics; 6th ed. CBS Publishers and Distributors, 2004:66-7. 2. Dasgupta, A., Butt, A., Saha, T.K., Basu, G., Chattopadhyay, A and Mukherjee A.  Assessment of malnutrition among adolescents: Can BMI be replaced by MUAC. Indian Journal of Medicine, 2010, 35, (2), 276-279. 3.Choudhary S, Mishra CP, Shukla KP. Nutritional status of adolescent girls in rural area of Varanasi. Indian J Prev Soc Med.2003; 34(1):53-61). 4.Shivramkrishna HR, Deepa AV, Sarithareddy M. Nutritional status of adolescent girls in rural area of Kolar district – A cross sectional study. Al Ameen J Med Sci. 2011; 4(3):243-246. 5.Soumyajit M. Chatterjee K, Kazi AM, Devidas G, Shampad AP; Assessment of Nutritional status of Rural Eraly Adolescent School Girls in Dantan-II Block Paschin Medinipur District, West Bangal; National Journal of community medicine, Vol.2, issue 1, pp 14-18 National J of com. Med. 2011; 2(1):14-18. 6. Deshmukh PR, Gupta SS, Bhasambe MS, Donge MC, Kaur S, Garg BS et al. Nutritional status of adolescents in rural Wardha; IJ Pediatr. 2006; 73(2):139-141. 7. Patil SN, Wasnik V, Wadke R. Health problems amongst adolescent girls in rural areas of Ratnagiri district of Maharashtra. Indian J of clinical and diagnostic research. 2009; (3):1784-1790. 7. Kaur TJ, Kochar GK, Agarwal T. Impact of nutrition education on nutrient adequacy of adolescent girls. Stud Home Comm Sci, 2007; 1:51-55. 8.Rahmathullah L, Underwood BA, Thulasiraj RD, Milton RC, Ramaswamy K, Rahmathullah R, Babu G. Reduced mortality among children in Southern India receiving a small weekly dose of vitamin A. N Engl J Med, 1990; 323: 929-935. 9.Singh S,  Kansal S, kumar A(2012) Assessment of Nutritional Status of Adolescent Girls in Rural area of District Varanasi; Indian  Journal of Research, Issue 6,30-34 10. Ramya R and Anooja Thomas(2015), Nutritional Status And Dietary Pattern Of Adolescent Girls Of Kottayam Taluk.  International Journal of Advanced Research. Volume 3, Issue 4: 949-955. 11.Mosarrof Hossain, Md. Tanvir Sarwar,  M. Hafizur Rahman, Shakh M. A. Rouf, Salim Raza, Asad Ud- Daula, Sabir Hossain(2013): A study on nutritional status of the adolescent girls at Khagrachhari district in Chittagong hill tracts, Bangladesh, American Journal of Life Sciences,Vol-1.Issue-6:278-282 12.Patanwar Pratibha, Sharma KKN(2013): Nutritional status of Kurmi adolescent girls of Raipur city Chhattisgarh, India; International Journal of Scientific and Research Publications, Volume 3, Issue 11:1-6. 13.Shahid A., Siddiqui F.R., Bhatti M.A., Ahmed M., Khan M.W. :(2009) Assessment of Nutritional Status of Adolescent College Girls at Rawalpindi. Annals; Vol. 15, Issue 1, Jan-Mar: 11-16 14. Tamanna S, Rana MM, Ferdoushi A, Ishtiyaq Ahmad SA, Rahman M, Rahman A,(2013) Assessment of Nutritional Status among Adolescent Garo in Sherpur District, Bangladesh; Bangladesh Journal of Medical Science Vol. 12 No.3: 269-275 15. Sushama A. Khopkar, Suvi M. Virtanen, and Sangita Kulathinal(2014,); Anthropometric Characteristics of Underprivileged Adolescents: A Study from Urban Slums of India. Journal of Anthropology :1-9

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411020EnglishN2018October26HealthcareContemporary Orthodontic Office:  A Review English1114Navaneetha NambiEnglish Xavier DhayananthEnglish N. R. ShrinivasanEnglish Shahul Hameed FaizeeEnglishTechnological changes affect most areas of our lives, and our orthodontic practices are no different. As these changes mount, orthodontists and their teams have many questions. How can we possibly adapt to these rapid changes? Is now the right time, or should we wait to see what others do who know more than me? Will something better come along? Will we be left behind if we don&#39;t jump in now? Areas currently being influenced by technology in our orthodontic practices include education, personnel management, marketing, communication, diagnosis and treatment planning, and treatment. We have chosen to use an integrated technology solution when possible to avoid many of the above problems and to provide a certain sense of comfort for my team and myself by having a single source for customer support. We will describe our choices in this article.  EnglishPaperless orthodontic office, Computers ion orthodontics, Digital management of orthodontics, Paperless practiceINTRODUCTION When orthodontists discuss the practice of the future, the conversation usually turns to the problem of eliminating paper from daily operations. In a busy practice, trying to keep track of patient files and treatment records is both cumbersome and difficult. Many of today&#39;s practices use computers in selected areas, but are far from "paperless". Several progressive orthodontists, however, have discovered that a paperless operation can be a reality, and that it does increase practice efficiency. This article will examine the factors involved in making such a transition towards establishing a Contemporary Orthodontic Office. TECHNOLOGICAL CONSIDERATIONS As a famous quote given by Bill Gates “A computer was born to solve problems that did not exist before.” “The great thing about a computer notebook is that no matter how much you stuff into it, it doesn&#39;t get bigger or heavier”. Disadvantages of conventional Orthodontic office:- Maintaining records, Preserving Casts without getting damaged. Space constraint due to increasing quantity of records. Confusion within patients with same name All these reduce the efficiency of the working environment. Adds stress to the doctors. IDEAL REQUIREMENTS FOR PAPERLESS OFFICE The first requirement for paperless operation is that you must be willing to change your practice into a high-tech operation. Must be easy to use, Stable & compatible with other software. It must also have the capacity to be upgraded and to be adaptable to work with new software and hardware. The ability of a system to produce automatic letters or information that is otherwise laborious or difficult to collect will encourage the user to enter the data. Ability to search for information quickly. All paper records and manual systems must be replaced by a central, computerized practice management program. Thus, all patient records will be available at every workstation, to everyone with access to the computer system. These records include: Demographic (patient information forms) Diagnostic (health histories, photographs, models, x-rays) Treatment (charts, plans, notes) Scheduling (appointment book) Financial (ledger cards) Ancillary tools may include imaging, cephalometrics, insurance-benefits data bases, credit reporting, scanning, inventory and electronic ordering, and CD-ROM systems for patient education, case presentations, and staff training. All operations, including treatment delivery, are centralized around the primary computer program. Even if you do not want to go completely paperless, integrating all the practice tools into one system will enhance your efficiency. The computer company entrusted to provide such a system must have: Considerable experience with paperless operations. A record of providing software that keeps up with the changing needs of orthodontic practices. A program that does not limit choices to the products of any one company, which may be popular today, but fail to keep up with new technology. A program allowing selection of ancillary practice tools, such as imaging systems,  that are compatible with present or anticipated equipment. An efficient method of electronically converting existing patient data to the new format. Systems designed to minimize hardware failures and downtime. Systems designed to accommodate growth of the practice and staff. DISCUSSION:- MANAGING PATIENT DATA A Complete database of patients and other consultants is available to be viewed from every work station. Everything that you need to know about a patient should be neatly displayed. Allows you to communicate directly with patients automatically via sms or e-mail. View financial summaries, appointment recalls and post-dated data immediately on patient files. FINANCIAL CONSIDERATIONS The initial investment in hardware and software is the first cost factor to be considered in developing a paperless office. Ongoing expenses will depend on the system selected and the size of the practice. PHYSICAL CONSIDERATIONS An axiom in office design is that "work patterns determine the floor plan". Therefore, the first step in designing a perfect floor plan whether the practice is paperless or not is for the doctor and staff to step back and analyze the way they work. It is important to recognize and build on efficient work patterns, but to be willing to substitute new methods in areas of weakness. Many offices that are now using computers are actually in an intermediate stage toward becoming a paperless office. The same basic floor plan can be converted to a paperless office without much structural change. Switching to a paperless mode can be gradual, or with the right system and proper preparation, can be done immediately. When establishing a new facility, it is usually advisable to make a complete change before moving into the new office. Many specific needs of the practice must be determined when making a transition within an existing facility: Number and location of work stations Location of the file server Operating system requirements. Present and future software requirements The number and location of work stations becomes important in the determination of the computer hardware and the capacity required. Automated records should be available for access at the following locations: Front desk Financial/business areas Key areas throughout the operatory Chairside units Satellite offices Doctor&#39;s home When practical, the main server should be located near the center of the office, thus reducing the distance to the work stations. If the server is placed in a closet, as is often done, the closet must be well ventilated. A vent in the door is acceptable, because a server does not make enough noise to interfere with clinical operations. If the server is located in a mechanical room, it should be mounted on a wall rather than placed on the floor, to avoid water contamination from the suction, compressor, or other equipment. A myriad of practice management software programs are available, including everything from electronic scheduling to computerized time clocks and payroll systems. The management system should have the ability to link branch offices if necessary. In addition, if the doctor has access to patient information at home, it will eliminate the need to take patient charts out of the office, with the potential of lost or misplaced records. Office work can then be done at home on a laptop computer. INSTALLATION AND WIRING If the building is under construction, the cable or conduit should be installed during framing, before the walls are finished or concrete is poured. Wiring from the server can pass upward into the ceiling space and be threaded down between walls to the various work-station sites. It is often efficient and economical to route the wiring through concrete or wooden floors, but if you have a concrete floor and are on the ground level, trenching will be required to gain access to chairside units or to central islands in an open-bay operatory. The computer-wire conduit can be placed in the same trench used to supply operatory units with air, water, and electricity. The design should allow ready access to conduits or wires, since future technological advances may require changing the wiring. PATIENT FLOW The floor plan should indicate the primary location Problems that can interrupt patient flow include inability to locate patients, questions about treatment status, and lost records or charts. An effective paperless practice carefully controls patient flow and keeps doctors and staff fully informed of each patient&#39;s location and treatment status. Upon arrival, the patient checks in the reception area. This information is instantly relayed to the on-deck screen, which displays patients in the order they are normally taken-first by appointment time, and second by check-in time. The patient may be seated in the reception room, as is often done with adults, or may proceed to an on-deck area in view of the assistants in the operatory. Any screen can be checked to determine whether a patient is early or late, or to find out who is seated in which chair. Thus, the doctor always knows which chairs require his or her presence, and in what order. RECORDS STORAGE Traditional office designs allot considerable space to paper product storage and filing cabinets, increasing the practice&#39;s rental costs. As storage space fills up, many large practices have to purge their files two to three years into retention. With more practices prescribing long-term retention, however, records must legally be kept longer than in the past. In a paperless office, the scanning system stores all patient records in the computer. The storage problem is eliminated, and long-term retention information can be instantly retrieved. Scanned records can be transferred to off-site storage on a regular schedule, or whenever computer disk capacity is reached. The doctor or a designated staff member can leave the office each day with a backup copy of all the patient records in the practice an important security advantage. In case of a disaster such as fire or flood, the complete practice records can be available for use within hours. Orthodontists using paperless systems report backing up their patient records every month and storing them off-site at archiving services. While alteration of traditional paper records can be a legal issue, this electronic system prevents any entries on treatment charts from being altered after storage. REDUCING STRESS As with any major change, a few problems will arise during the transition to a paperless operation, and a learning curve will be experienced. Nevertheless, those who have made this transition report that any initial apprehension is quickly overcome by the reduced stress of treating patients. Instant access to patient data by any staff member, at work stations throughout the office, will be a welcome improvement over past routines. Now, pictures of pretreatment casts or changes in facial profiles could be instantly flashed on the chairside screens. Increased interaction and communication with patients and parents naturally occurred, especially in explaining treatment progress. CD-ROM educational materials on brushing techniques and the like could be used routinely. Paperless records also offer advantages outside the office. Some of the doctors have found it convenient to update patient records at home, at night and on weekends. They feel this gives them an unhurried time in which to review treatment plans or enter notes regarding treatment and progress. One way to do this is to connect a home computer to the office system via modem. Another method is to take the entire office data base home on a laptop computer. After changes are made, the revised data is simply loaded back into the office system. SHORTFALLS OF THIS PAPERLESS OFFICE Since everything is computer based, we also need to have proper back-up facility for all the records. All the computers are prone to virus attacks and loss of data due to crashing of the system should be avoided. Hence ideal back-up plan should be kept and should be periodically updated with necessary changes. CONCLUSION A permanent conversion to paperless office is a significant change. Doctors and staff members who have made the change, however, believe it increases practice efficiency, enhances patient communication, and reduces stress in the practice. The computer system actually elevates the level of personal contact with patients, instead of reducing it. Advantages being, hassle free record maintenance, patient follow-up becomes easier, which are two main laborious process in an Orthodontic office. Before choosing a company or system, you should be certain that it can be integrated with all your other electronic tools, such as imaging. Only the proper hardware and software will make it possible to achieve the ultimate goal of the paperless practice. ACKNOWLEDGEMENT:- We thank our fellow staffs of our Department of Orthodontics and dentofacial orthopedics, Sathyabama Dental College & hospital. Englishhttp://ijcrr.com/abstract.php?article_id=2536http://ijcrr.com/article_html.php?did=25361.Lewis, C.A. and Moorish, J.A. Jr.: The "paperless" orthodontic practice, Orthod. Prod.2:44-47, 1996. 2.Hamula, W.: Orthodontic Office Design: Developing a floor plan, J. Clin. Orthod. 18:719-725, 1984. 3.Lewis, C.A.: System needs analysis: Part II--Evaluating orthodontic software, Orthod. Prod. 3:38- 44, 1997. 4. Weekes WT, Computers and the orthodontist, Aust Orthod J. 1993 Oct;13(1):47 5. Sloan RF, Computer applications in orthodontics, Int Dent J. 1980 Sep;30(3):189-200. 6.  Ned Tijdschr Tandheelkd. 2003 Jan;110(1):25-30. Digitalizing in the orthodontic practice Schols JG 7. Müller H, Michoux N, Bandon D, Geissbuhler A, A review of content-based image retrieval systems in medical applications-clinical benefits and future directions, Int J Med Inform. 2004 Feb;73(1):1-23. 8. Duffy P, McLendon K., Understanding computers or some of the things you always wanted to know about computers ... but were afraid to ask, J Am Med Rec Assoc. 1991 Aug;62(8):37-51, 54.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411020EnglishN2018October26HealthcareRole of Candida in Catheter Associated Urinary Tract Infection English1519Swati SahaiEnglish Amit KumarEnglishBackground: UTI in hospitalised patients due to Candida spp. is becoming increasingly common in ICU setting. There is always a dilemma as to differentiate colonisation from true infection and whether to treat candiduria or not. The choice of antifungal is also controversial due to low urinary concentration of many antifungal drugs. Objective: This study was conducted to assess the significance of Candida spp. as the causative agent of symptomatic CAUTI in medical ICU patients and perform microbiological characterisation of Candida and their antifungal susceptibility pattern. Methods: A total of 100 patients admitted in medical ICU and put on Foley’s catheter were included in the study and followed up for the development of symptomatic CAUTI. The urine samples from the catheter were collected on day 1 and then on day 3,5,7,10,14 and every weekly till the patient was discharged, expired, catheter removed or developed bacteriuria or candiduria. The samples positive for Candida spp. were identified and processed as per standard guidelines. Results: In this study, it was found that 23% (6/26) of the symptomatic CAUTI was caused by Candida spp. Candida species comprised 15% of the causative organisms. Among the candida species, non-albicans Candida spp. contributed to 83.3% of the isolates and only 16.7% of isolates were Candida albicans. All Candida isolates were sensitive to fluconazole, voriconazole, amphotericin B and itraconazole. Conclusion: Symptomatic catheter associated urinary tract infection with Candida spp. is becoming increasingly common. Among Candida spp., non-albicans Candida is emerging as the predominant pathogen causing CAUTI. EnglishCandida, Candiduria, Catheter associated urinary tract infection, Nosocomial, Intensive Care UnitINTRODUCTION             Catheter associated urinary tract infection (CAUTI) is the most common hospital acquired infection which accounts for more than 80% of nosocomial urinary tract infections (UTIs)[1]. The risk factors associated with CAUTI in adults mainly include intensive care unit (ICU) admission, broad-spectrum antibiotics, diabetes mellitus, increased age, and female sex.[2,3] The microorganisms causing CAUTI range from Gram negative bacteria to Gram positive cocci to Candida. UTI in hospitalised patients due to Candida spp. is becoming increasingly common in ICU setting[27]. There is always a dilemma as to differentiate colonisation from true infection and whether to treat candiduria or not[28]. Symptomatic CAUTI is considered when symptoms / signs consistent with UTI exists along with candiduria in a catheterized patient [2]. The signs and symptoms either are localized to the urinary tract or can include otherwise unexplained systemic manifestations, such as fever[2]. The accepted threshold for bacteriuria/candiduria varies from 103colony forming units per millilitre (cfu/mL) to 105 cfu/mL[2]. The choice of antifungals is also controversial due to low urinary concentration of many antifungal drugs[28]. This study was conducted to assess the significance of Candida spp. as the causative agent of symptomatic CAUTI in medical ICU patients and perform microbiological characterisation of Candida and their antifungal susceptibility pattern. MATERIALS AND METHODS             Approval of the Institutional Ethics Committee was obtained before starting the study. Informed written consent was taken from all the patients included in the study. This was a cross-sectional study conducted at the Institute of Microbiology, Madras Medical College in association with Medical ICU, Rajiv Gandhi Government General Hospital, Chennai. It was of one year duration from October 2014 to September 2015 which included a total of 100 patients admitted to medical ICU. Those who were 18 years and above and put on Foley’s catheter were included in the study. The exclusion criteria included patients less than 18 years of age, those catheterised prior to admission in ICU, those confirmed to have UTI on 1st day and whose Foley’s catheter was removed or who were discharged before the 3rd day of catheterisation.             Data were collected from the patients using a preformed structured questionnaire. Physical examination findings and details of clinical diagnosis was also noted. Daily examination of the patients were done to look for any evidence of urinary tract infection. The patients were followed till they developed bacteriuria/candiduria or discharged, expired or catheter was removed. Patients who were shifted to different ward were followed for up to 48 hrs for the developments of symptoms of CAUTI [3]. Urine specimens were collected aseptically from the Foley’s catheter, approximately (minimum) 3ml of urine was taken as a sample in a flat bottomed universal container. The samples were taken to laboratory within 1 hour of collection. Day 1 sample was taken to rule out prior presence of UTI. The samples were repeated on 3rd, 5th, 7th, 10th, 14th day and then every weekly until catheter removal, or patient developed bacteriuria, or until discharge/death of the patient [1,3]. The patients were diagnosed as symptomatic CAUTI as per Centre for disease Control (CDC) guidelines January, 2014 which included  the development of UTI caused by Candida spp., with a culture of ≥103 CFU/ml on a specimen collected at least 48 hrs after hospital admission and a previous Candida spp.-negative culture [2]. Direct Gram’s stain of uncentrifuged urine was done to observe for the presence of bacteria or candida. Detection of nitrites and leucocyte esterase was done on uncentrifuged urine using dipstick test. Then the urine sample was centrifuged at 3000rpm for 3-5 minutes. A wet mount of the sediment was done and the number of pus cells / high power field was counted under 40 x objective. More than 5 WBC/hpf was considered significant for diagnosing CAUTI [1,4].             The specimens were cultured by semi-quantitative method using Mac Conkey Agar and Blood Agar as culture medium. The plates were read after 24 hours of incubation for any growth[1].  Based on colony morphology on 5% sheep blood agar and no growth on Mac Conkey agar, the colonies were suspected to belong to Candida species. Gram stained smear showed Gram positive budding yeast cell with pseudohypahae. Candida was speciated based on germ tube test as Candida albicans and non-albicans Candida[5,6].  The candida species were identified on Dalmau plate culture method by the presence of hyphae, blastoconidia and chlamydospores [7,8]. Further speciation of Candida was done by sugar fermentation and sugar assimilation tests [5,6,8]. In sugar fermentation tests, 2% sugars were used which included glucose, maltose, sucrose and lactose. For sugar assimilation test, carbohydrate discs -glucose, maltose, sucrose, lactose, cellibiose, galactose, trehalose, raffinose, xylose, inositol and dulcitol were placed on the yeast nitrogen agar and incubated for 24-48 hours at 25°C. The assimilation of the particular carbohydrate by the yeast was indicated by the growth around the discs. The pattern of assimilation was noted [1].             Speciation of Candida spp. was also done using Candida Chrom Agar [5,8,9]. Candida spp. was subcultured onto Sabouraud’s Dextrose Agar and then streaked onto Chrom agar plate. This was incubated for 48 hours at 37°C and the colour and morphology of the colonies were noted.            The antifungal susceptibility test was done by disc diffusion method and minimum inhibitory concentration (MIC) method [10,11]. The drugs fluconazole (25µg) and voriconazole (1µg) were tested by Kirby Bauer Disk diffusion method on supplemented Mueller Hinton Agar which contained Mueller Hinton agar supplemented with 2% glucose and 0.5 μg/ml methylene blue. MIC by microbroth dilution was done for fluconazole, itraconazole and amphotericin B. RESULTS  In this study, among 100 patients enrolled, 26 developed symptomatic CAUTI. It was found that 23% (6/26) of the symptomatic CAUTI was caused by Candida spp. A total of 40 organisms were isolated. Majority of the organisms isolated belonged to Enterobacteriaceae (34.5%) and nonfermenters (32.5%). Candida species comprised 15% of the causative organisms. Among the candida species, non-albicans Candida spp. contributed to 83.3% of the isolates and only 16.7% of isolates were Candida albicans. Among non-albicans Candida, 2 patients had Candida tropicalis and one patient each had Candida krusei, Candida parapsilosis and Candida glabrata isolate. All Candida isolates were sensitive to fluconazole, voriconazole, amphotericin B and itraconazole. DISCUSSION Catheter associated urinary tract infection is the commonest device associated nosocomial infection. The rate of device associated infections shows variation in India. According to a study conducted by Angshuman Jana et al (2015) [12], the incidence was 31.85%. A study by Priya Datta et al (2014) [13] found the CAUTI rate as 10.75% , by Kamat et al (2009) [14] as 33.6%, and Al Jebouri et al (2006) [15] as 28.1 %.  In this study, out of 100 patients, 26 patients were diagnosed to develop symptomatic CAUTI during their course of hospitalisation. Therefore, the incidence was 26% and the CAUTI rate was calculated as 25.67 per 1000 catheter days. It is thought that candiduria is very common in hospitalised patients [16,17,18,19] and is mainly due to antibiotic usage [20]. In one of the point prevalence survey done in 228 hospitals from 29 European countries, 9.4% of nosocomial UTIs were found to be caused by Candida spp. The incidence of candiduria varies with hospital setting and is most common in ICUs [19] and among those in burn units [34]. A study conducted by N. Febre et al (1999) found Candida spp. in 18.6% of urine specimens from patients with indwelling urinary catheters in ICU. Other studies report that 11 to 30% of nosocomial UTIs are caused by Candida [22,23]. In the present study, 23% of the symptomatic CAUTI in medical ICU was caused by Candida spp. and it comprised 15% of the total causative agents. In most studies, C. albicans dominates and accounts for 50% to 70% of all Candida-related urinary isolates, followed by C. glabrata, and C. tropicalis, which is the third most common species [16,21].  In a large multicentre study from Spain, C. albicans was recovered in 68%, followed by C. glabrata (8%) and C. tropicalis (4%). However, various studies show a steady increase in the incidence of non-C. albicans strains producing nosocomial infections such  as those conducted by De Francesco MA et al (2007) [24], Horn DL et al (2009), [25] and Xess I et al (2007) [26]. In a study conducted by Manisha Jain et al (2011) [27], non-albicans Candida spp. (71.4%) was the predominant pathogen causing CAUTI. Similar findings were seen in this study. Among Candida isolates, non-albicans Candida spp. emerged as the predominant isolate accounting for 83.3%. These included Candida tropicalis (2), C. parapsilosis (1), C. krusei (1) and C. glabrata (1). Antifungal susceptibility in candiduric patients depends largely on the infecting strains. In this study, all Candida isolates were sensitive to fluconazole, voriconazole, amphotericin B and itraconazole. CONCLUSION Symptomatic catheter associated urinary tract infection with Candida spp. is becoming increasingly common. It is usually difficult to ascertain the difference between Candida colonization and infection. Diagnosis mainly depends on the symptoms of UTI along with pyuria and high colony Candida counts in the urine. Among Candida spp., non albicans Candida is emerging as the predominant pathogen causing CAUTI. Based on clinical setting, the relevance of candiduria must be determined and appropriate decision should be taken for the need of antifungal therapy. There is a need for further studies to determine regime for such patients so as to address some of the unanswered questions of when to treat, whom to treat and how long to treat. ACKNOWLEDGEMENT I wish to express my sincere thanks to our Dean, Dr.R.Vimala M.D., for permitting me to use the resources of this institution for my study. I would like to thank the Director I/C & Professor, Dr. Mangala Adisesh, M.D.for her guidance and support throughout the study. My sincere thanks to Prof. Dr. Ragunanthanan, M.S., Professor, Institute of Internal Medicine, for permitting to carry out my study. I would like to thank Dr. Amit Kumar, MD(Medicine), Senior Resident, Southern Railway Headquarters Hospital, Chennai for his invaluable suggestions and continuous support throughout my study. I owe special thanks to Dr. S. Vasanthi, M.D., Professor, Institute of Microbiology for her support, guidance in my study and for being a source of inspiration in my endeavours. I extend my whole hearted gratitude to our Assistant Professor Dr. David Agatha M.D. for her valuable guidance and immense support in my study. I would also like to thank our professors and assistant professors for their valuable guidance in my study I hereby express my gratitude to all the technical staff for their help throughout my study. I don’t have any conflict of interest. I acknowledge the immense help received from the scholars whose articles are cited and included in references of this study. I am 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. Englishhttp://ijcrr.com/abstract.php?article_id=2537http://ijcrr.com/article_html.php?did=2537 Betty a Forbes, Alice S Weissfeld, Daniel F. Sahm. Bailey and Scott diagnostic microbiology, 13th edition 2013; 919-930. Device-associated module, Cauti: January 2014: available at: http://www.cdc.gov/nhsn/pdfs/pscmanual/7psccauticurrent.pdf; 26.07.2014; 16:39 C. M. Poudel, g. Baniya, b. M. Pokhrel. Indwelling catheter associated urinary tract infection. Journal of institute of medicine, December, 2008; 30:3. Monica Cheeseborough; district laboratory practice in tropical countries- part 2; 2nd edition; Cambridge university press, 2006; pgs 105-115 Jagdish Chander. Textbook of Medical Mycology, 3rd edition, Mehta publishers, 2009. Page 266-290 Jagdish Chander. Textbook of Medical Mycology, 3rd edition, Mehta publishers, 2009. Page 508-513 Fran fisher, norma b. Cook. Fundamentals of diagnostic mycology. Edition 1, saunders. 1998. pg 196-212 Davise H. Larone. Medically important fungi-a guide to identification. 5th edition.asm press.2011. Pgs 115-126 Chrom agar candida; http://www.chromagar.com/clinicalmicrobiology-chromagar-candida-focus-on-candida-species-22.html#; 22.07.2015; 11:00 Method for antifungal disk diffusion susceptibility testing of yeasts; approved guideline—second edition, CLSI document 2009 Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard—third edition, clsi document. 2008  Angshuman Jana, NK Pal, Arijit Majumdar, Jayeeta Mitra, Anirban Jana, Soumali Biswas, Babita Bag device-associated infection rates and median length of acquiring device-associated infection in an intensive therapeutic unit of an Indian hospital : Journal of medicine in the tropics: Year: 2015 | volume : 17 | issue : 2 | page : 97-102 Priya Datta, Hena Rani, Rajni Chauhan, Satinder Gombar, and Jagdish Chander. Health-care-associated infections: risk factors and epidemiology from an intensive care unit in northern India. Indian j anaesth. 2014 jan-feb; 58(1): 30–35. Kamat U S, Ferreira A, Amonkar D, Motghare D, Kulkarni M S. Epidemiology of Hospital Acquired Urinary Tract Infections in a Medical College Hospital in Goa. Indian j urol 2009; 25:76–80. Al-Jebouri, O.A.H. 2006. The relationship between urinary caliculi types and urinary tract infections among patients in Tikrit District. M. Sc. Thesis, college of medicine, tikrit university, tikrit. Alvarez-Lerma, F., J. Nolla-Salas, C. Leon, M. Palomar, R. Jorda, N. Carrasco, and F. Bobillo. 2003. Candiduria in critically ill patients admitted to intensive care medical units. Intensive Care Med. 29:1069-1076. [PubMed] Kauffman, C. A., J. A. Vazquez, J. D. Sobel, H. A. Gallis, D. S. McKinsey, A. W. Karchmer, A. M. Sugar, P. K. Sharkey, G. J. Wise, R. Mangi, A. Mosher, J. Y. Lee, and W. E. Dismukes. 2000. Prospective multicenter surveillance study of funguria in hospitalized patients. The National Institute for Allergy and Infectious Diseases (NIAID) Mycoses Study Group. Clin. Infect. Dis. 30:14-18. [PubMed] Richards, M. J., J. R. Edwards, D. H. Culver, and R. P. Gaynes. 2000. Nosocomial infections in combined medical-surgical intensive care units in the United States. Infect. Control Hosp. Epidemiol. 21:510-515. [PubMed] Schaberg, D. R., D. H. Culver, and R. P. Gaynes. 1991. Major trends in the microbial etiology of nosocomial infection. Am. J. Med. 91:72S-75S. [PubMed] Weinberger, M., S. Sweet, L. Leibovici, S. D. Pitlik, and Z. Samra. 2003. Correlation between candiduria and departmental antibiotic use. J. Hosp. Infect. 53:183-186. [PubMed] Bougnoux, M. E., G. Kac, P. Aegerter, C. d&#39;Enfert, and J. Y. Fagon. 2008. Candidemia and candiduria in critically ill patients admitted to intensive care units in France: incidence, molecular diversity, management and outcome. Intensive Care Med. 34:292-299. [PubMed] Lundstrom, T., and J. Sobel. 2001. Nosocomial Candiduria: a review. Clin. Infect. Dis. 32:1602-1607. [PubMed] Richards, M. J., J. R. Edwards, D. H. Culver, and R. P. Gaynes. 2000. Nosocomial infections in combined medical-surgical intensive care units in the United States. Infect. Control Hosp. Epidemiol. 21:510-515. [PubMed] De Francesco, M. A., G. Ravizzola, L. Peroni, R. Negrini, and N. Manca. 2007. Urinary tract infections in Brescia, Italy: etiology of uropathogens and antimicrobial resistance of common uropathogens. Med. Sci. Monit. 13:BR136-BR144. [PubMed] Horn, D. L., D. Neofytos, E. J. Anaissie, J. A. Fishman, W. J. Steinbach, A. J. Olyaei, K. A. Marr, M. A. Pfaller, C. H. Chang, and K. M. Webster. 2009. Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry. Clin. Infect. Dis. 48:1695-1703. [PubMed] Xess, I., N. Jain, F. Hasan, P. Mandal, and U. Banerjee. 2007. Epidemiology of candidemia in a tertiary care centre of north India: 5-year study. Infection 35:256-259. [PubMed] Jain M1, Dogra V, Mishra B, Thakur A, Loomba PS, Bhargava A. Candiduria in catheterized intensive care unit patients: emerging microbiological trends. Indian J Pathol Microbiol. 2011 Jul-Sep;54(3):552-5. doi: 10.4103/0377-4929.85091. Bukhary Zakeya Abdulbaqi ; Candiduria: A Review of Clinical Significance and Management: Year : 2008 | Volume:  19 | Issue Number:  3 | Page: 350-360   

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411020EnglishN2018October26HealthcareComputer Aided Designing/Computer Aided Manufacturing in Dentistry (CAD/ CAM) — A Review English2024Sriram S.English Vidhya ShankariEnglish Yohan ChackoEnglishThe Computer Aided Designing Computer Aided Manufacturing (CAD/CAM) technology has become an increasingly popular part of dentistry over the past 25 years(3). The development of CAD/CAM technology in restorative dentistry has evolved drastically(4). By addressing the various dental office issues, digital impressions, with its enormous benefits, along with CAD CAM will make digital intraoral scanning into a routine procedure for most dental restorative procedures in the future. Furthermore, digital impressions reduce the number of visits required for treatment and also increasing effectiveness of the treatment in terms of accuracy and precision. Patients will thereby be benefitted from the comfort and the pleasant experience offered at the dental chair. This makes the restorations fabricated from the lab more consistent, requiring reduced chair time. With the popularization of such a technology, tremendous growth in several areas of dentistry that can potentially benefit from digital impression taking and digital models (restorative dentistry, prosthodontics, orthodontics , dental implantology) in the coming years and witness a true digital revolution in the field of  dentistry. This would make treatment planning more efficient with reduced discomfort and increased treatment efficiency. It allows the use of newer high strength materials with excellent biocompatibility combined with, provisions for aesthetic designs, improved precision of fit and longevity. However, these advantages must be balanced with the high initial cost of CAD/CAM systems and the need for additional training. The CAD/CAM systems offer the advantage of automation of fabricating dental restorations with increased quality over a short period of time. The Machinable ceramics are extremely suitable for the fabrication of restorations by CAD/CAM technique as they can be designed and milled in their soft pre-sintered condition and subsequently sintered to improve their physical properties. New high-strength core materials have been developed for all-ceramic restorations. However, most of the systems are limited to replacement of the anterior and premolar teeth, require large connector dimensions and may require the use of more technique - sensitive clinical procedures such as adhesive cementation. The article gives a critical insight on digital impressions and various CAD/CAM technologies available for fabrication of restorations and prosthesis English CAD/CAM, scanners, Steroelithography, Milling devices, Optical scannersINTRODUCTION: From its inception to now dentistry has covered great milestones in terms of invention and precision to provide us with better working conditions and increased comfort for both dentists and patients(1). The technological changes taking place over the years are truly revolutionizing the way dentistry is practiced and the manner in which dental laboratories are fabricating restorations(2). To add to the list of remarkable advancements is Computer aided design (CAD) and computer aided manufacturing (CAM) technology which allows the dentists to provide better care to the patients(1). The CAD CAM technology has become an increasingly popular part of dentistry over the past 25 years (3). More recently the development of CAD/CAM technology in restorative dentistry has evolved dramatically(4). This technology which is used in both the dental laboratories and the dental office can be applied to inlays, onlays, veneers, crowns, fixed partial dentures, implant abutments, even full mouth restorations and complete dentures. CAD CAM is also being used in orthodontics in the form of invisalign retainers. CAD/CAM technology was developed to overcome several drawbacks associated with the conventional lost wax techniques. The first was to eliminate shrinkage and expansions associated with wax and models. The second was to eliminate shrinkage and porosities associated with casting procedure. The third was to make restoration of tooth easier, faster, and more accurate in terms of precision and fit. In most cases CAD/CAM technology can used to provide restorations to patients within the same day. More than 30,000 dentists around the world own scanning and milling machines.  Worldwide more than 15 million restorations alone have been completed from its inception till date (2). With further advancements, dental CAD/CAM system have the potential to minimize inaccuracies in conventional technique and thus reducing the hazards of infectious cross- contamination associated with multistage fabrication of indirect restorations This review article gives a critical insight into the various CAD/CAM technologies which are being used to fabricate highly aesthetic and biocompatible restorations for restorative dentistry HISTORY: Computer aided-design and manufacturing (CAD/CAM) evolved from the engineering demands of aerospace and automotive industries. It was more than 2,300 years after Euclid that the first true CAD software, a very innovative system called "Sketchpad" was developed by Ivan Sutherland as part of his thesis at MIT in the early 1960s. Sketchpad was the world&#39;s first CAD software to be developed. Dr. Francois Duret was the first to develop dental CAD/CAM in 1971. He began to fabricate crowns with an optical impression of abutment followed by designing and milling (3). Some of the most important figures in dental CAD/CAM development are  Froncois Duret of France, Werner Mormann of Switzerland, Dianne Rekow of the United States and Matts Andersson of Sweeden2. Dr Mormann was the developer of the first commercial CAD/CAM system. He consulted with Dr Marco Brandestini, an electrical engineer, who came up with the idea of using optics to scan the teeth. By 1985 the team had performed the first chair side inlay using a combination of their optical scanner and milling device. They called the device CEREC an acronym for computer assisted ceramic reconstruction. Dr Anderson developed the Procera (now known as Noble Procera, Noble Biocare, and Zurich, Switzerland) method of manufacturing high precision dental crowns in 1983. He was also the first person to use CAD/CAM for composite veneer restorations EVOLUTION OF CAD/CAM SYSTEMS: •1971: Duret&#39;s experimental research. • 1979: Heitlinger Rodder&#39;s experiment • 1980: Mormann & Brandestini started developing the CEREC system. • 1984: Fujita concerned with transferring the manufacturing processes to the dental care industry. • 1985: Siemens Dental, today SIRONA, creates the CEREC system    (Germany). • 1989: CDS Dental (Switzerland) creates DCS Precident and Nobel Biocare    AB creates PROCERA. • 1990: Creation of Digident (Girrbach Dental GmbH, Pforzheim, Germany) • 1991: Creation of Celay (Mikrona Technologies, Spreitenbach, CH). • 1993: Creation of Cicero (Ciceron Dental Systems, Hoorn, NL) • 1995: Creation of Cercon Smart • 2001: Creation of Etkon (etkon AG, Gräfelfing, D)   Creation of Everest (KaVo, Leutkirch, Germany),   Creation of Lava (3M ESPE AG, Germany),   Creation of EDC (Wieland Dental, Germany),   Creation of Wol-Ceram (WolDent GmbH, Ludwigshafen, D.) • 2002: Creation of Bego Meddifacturing (Medical Bego, Bremen) • 2003: Creation of Perfactory (envisiontec, Gladbeck, D); creation of the    Xawex Dental System (ZrN process, I-Mes, Eiterfield • 2005: Creation of Dental Designer 3Shape (3Shape A/S, Copenhagen, DK); Creation of ADG - SW General Subdirector - Software for Automated    Prosthesis Generation, Dental GmbH, Pforzheim, Germany) •2007- Cadent iTero system •2008-E4D Dentist system •2008- Lava chairside oral scanner (COS) ² CAD/CAM DISCUSSION: TRIAD AND STAGES OF CAD/CAM FABRICATION Fabrication of a restoration with CAD/ CAM system has three functional components: A. Data Capture B. Restoration design C. Restoration fabrication Data acquisition involves making an optical impression of the preparation. It can be done with the help of various intraoral scanning devices such as intraoral camera, mechanical or optical digitizers’ etc. Restoration designing includes designing the restoration digitally using CAD software. Some of the CAD softwares can design the restoration nearly matching the excellence of restorations produced by master dental technicians. Restoration fabrication includes milling of the restoration using CAM software with the help of milling machines. Almost all the systems rely on cutting the restoration from a prefabricated block known as subtractive approach. While as an alternative additive CAM approach can also be used in which layering of the material is done to produce a restoration. COMPUTERIZED SURFACE DIGITIZATION/SCANNING After cavity preparation, this process involves making an optical impression by surface digitizing or scanning. 3D-surface digitizing or scanning methods are separated into: Direct (at the tooth). Indirect methods (via impression making &model fabrication) 1. Various surface digitization techniques which have been explored are: Laser scanning. Computed tomography. Magnetic resonance imaging. Ultrasound. Contact profilometry. The term scanner in dentistry means data collection tools that measure three dimensional jaw and tooth structures and transform them into digital data sets5. There are two different types of scanners: • Optical scanners • Mechanical scanners a) Optical scanners The optical scanners works on the principle of collecting three dimensional data by a process called “triangulation procedure”. Here, the light source and the receptor unit are held at a definite angle to one another. The computer uses this relationship to calculate a three dimensional data set from the image on the receptor unit. The light source could be white light projections or a laser beam for illumination. The following are examples of optical scanners on the dental market5: - Lava Scan ST (3M ESPE, White light) - Everest Scan (KaVo, White light) - es1 (etkon, Laser beam). The recently introduced Nobel Procera scanner uses a newer technology called Conscopic holography technology. Among the various methods the manufacturer describes this technology as superior to triangulation as projected and reflected beams travel the same linear pathway. This allows scanning of steep slopes of up to 85 degrees with ease b) Mechanical scanner: In this type of scanner, the master cast is read mechanically by means of a ruby ball and the three-dimensional data is acquired.  Currently Procera Scanners Piccolo and Forte (Nobel Biocare) are the only examples for mechanical scanners available in dentistry. Advantages: Mechanical scanners have a relatively high scanning accuracy and the diameter of the ruby ball is set to the smallest grinder in the milling unit, so that all data collected by the system can be milled. Disadvantages: The highly complicated mechanics involved in the system, makes the apparatus very expensive and the processing time is more compared to optical scanners(5). Mechanical digitizers must capture the entire surface of a prepared tooth accurately thereby maintaining the position of the device to the tooth. Many mechanical digitizers are exceptionally sensitive to any motion. Slight movement of patient during data acquisition would compromise the quality of the data, ultimately leading to a restoration that compromise on the fit(6). In most instances, the scanner used to capture data is an integral part of the CAD/CAM system and operates only in combination with CAD software along with it. Commercially available scanners: 1. CEREC® – by Sirona Dental System GMBH (DE) 2. iTero – by CADENT LTD (IL) 3. E4D – by D4D TECHNOLOGIES, LLC (US) 4. Lava™C.O.S. – by 3M ESPE (US) 5. IOS Fast Scan – by IOS TECHNOLOGIES, INC. (US) 6. DENSYS 3D – by DENSYS LTD. (IL) 7. DPI-3D – by DIMENSIONAL PHOTONICSINTERNATIONAL, INC. (US) 8. 3D Progress – by MHT (IT) and MHTOptic Research AG (CH) 9. Direct Scan – by HINT - ELS GMBH (DE) 10. Trios – by 3SHAPE A/S (DK) COMPUTER AIDED DESIGNING  The restorations are designed using Special designated software called CAD software that is provided by the manufacturers for the design of various 3D dental restorations on computer s(5, 7). The operator enters the data acquired from the scanning process and confirms the features of the preparation. These data are stored in a special format called standard transformation language (STL) data5. When the designing of the restoration is completed by the software, it is then transformed into virtual model using specific set of commands. Even in the most automated system , the operator  has the option to modify the automatically designed restoration to customize it to their requirement. Once the restoration is designed in the CAD, the CAM unit, fabricates the final restoration(8) COMPUTER AIDED MANUFACTURING CAM uses the computer generated path to shape a restoration. Earlier systems relied almost on cutting the restoration from a prefabricated block using burs, diamonds or diamond disks. This approach is termed as “Subtractive method”. Subtractive fabrication can create complete shapes efficiently and however with large expense of material being wasted. Processing /milling devices are categorized by means of the number of milling axes: • 3-axis devices • 4-axis devices • 5-axis devices A) 3-axis milling devices: Three axes milling device has degrees of movement in the three spatial directions. The milling points are defined by the X -, Y -, and Z– values. A milling of subsections, axis divergences and convergences are not possible. This requires a virtual blocking in such Areas of the milling block. All 3-axismilling devices used in the fabrication of dental restorations can turn the component by 180° in the course of processing the inner and the outer aspect of the restoration. The advantages of 3 axes milling devices are short milling times and simplified control by means of the three axes. Hence, such milling devices are usually less costly compared to those with a higher number of milling axes. Examples of 3-axis milling devices are: in Lab (Sirona), Lava (3M ESPE), Cercon brain (Degu Dent). b) 4-axis milling devices In four axes milling devices, addition to the three spatial axes, the tension bridge rotationis included as the fourth component. Hence it is possible to adjust long span bridges with a large vertical height displacements and it also facilitates in saving material and milling time compared to three axes milling devices. Example: Zeno (Wieland-Imes). c) 5-axis milling devices With a 5-axis milling device there is, in addition to the four spatial dimensions, rotating the milling spindle is included as 5th axis. This facilitates the milling of complex anatomies with subsections, for example, lower jaw FPDs with converging abutment teeth (end molar tipped towards the medial plane, or also crown and FPD substructures that, as a result of anatomically reduced formation, demonstrate converging areas in the exterior of the framework. Example in the Laboratory Area: Everest Engine (KaVo). The quality of the restoration need not necessarily increase with the number of milling axes. The increased number of milling axes provides benefit only in terms of fabricating complex restorations and not relating to the quality of the restoration. The quality of restorations is more from the result of the digitalisation process, data processing and production process than the milling devices. (5). MILLING VARIANTS a) Dry processing Dry processing is used with zirconium oxide blocks with a low degree of pre-sintering. This provides several benefits: • No moisture absorption by the block, as a result of which there are no initial drying times for the zirconium oxide frame prior to sintering. • Low investment cost for the milling unit Disadvantages: • The lower degree of pre-sintering causes higher shrinkage values for the restoration. Some manufacturers also offer the option of milling resin material in a dry milling process [Example:Zeno 4030 (Wieland-Imes), Lava Form and Cercon brain]. b) Wet milling In this type of milling process the diamond or carbide cutter is protected by a spray of cool liquid usually water against overheating of the milled material. This kind of processing is necessary for all metals and glass ceramic material in order to prevent damage to the final restoration through heat development. ‘Wet’ processing is recommended, if zirconium oxide ceramic with a higher degree of pre-sintering is employed for the milling process. A higher degree of pre-sintering results in a reduction of shrinkage and facilitates less sinter distortion. Examples: Everest (KaVo), Zeno (5, 8). Selective laser sintering: Selective laser sintering (SLS) is an additive manufacturing technique used for the low volume production of prototype models and functional components. It starts by converting the CAD data in series of layer. These layers are then transferred to the additive selective laser sintering machine which starts to lay the first layer of powder. As the laser scans the surface, the material gets heated and fuses together. Once the single layer formation is completed, the powder bed is lowered and the subsequent layer of powder is rolled out smooth & subjected to laser. Hence a layer by layer formation of the object takes place (1) Combination of additive and subtractive CAM approaches: In this initially an enlarged metal die is milled based on the 3D data of the prepared tooth by subtractive approach. Then powder is compacted under pressure on to the metal die, creating an oversized block by means of an additive approach; the block then is milled away to create the contours of the restoration. The oversized restoration is removed from the die and sintered to make the material as dense as possible and to shrink it to its final actual size. Additive electrophoretic dispersion method: It involves the application of slurry of alumina powder onto the master die to create a coping. The operator then manually trims away the excess material that extends beyond the margin. The outer contour of the restoration is shaped using a subtractive CAM approach. The operator then removes the coping from the die and then infiltrates glass(9). Additive rapid prototyping technique: It is also known as 3D printing. It is being used to design and print a wax pattern of a restoration (WaxPro printer of the Pro 50 system). It operates similar to an inkjet printer. The machine builds wax patterns of frameworks and full crowns The wax pattern is then cast or pressed in the same manner similar to conventional waxed restorations. Advanced printing units can be used to print resin type material instead of the wax. This system has wide range of applications than of most CAD/CAM systems for dental restorations; it can be used to fabricate auricular prostheses(8). Stereolithography Stereolithography (SLA) is the most commonly used rapid prototyping technology. It is the technique used for  creating 3D objects in which a computer controlled laser beam is used to build up the required structure layer by layer (9,10) CONCLUSION: In current scenario CAD/CAM technology has become a core part of dentistry with more number of restorations being fabricated. With the advancement taking place digital systems and CAD/ CAM has the potential to replace the conventional technologies. With this restorations can be fabricated quickly, with better properties and esthetic demands of the patient. ACKNOWLEDGEMENTS: The authors acknowledge the immense help received from scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors/ editors of all those articles, journals, and books where the literature for this article has been reviewed and discussed CONFLICT OF INTEREST: NIL Englishhttp://ijcrr.com/abstract.php?article_id=2538http://ijcrr.com/article_html.php?did=25381. Takashi M, Yasuhiro H, Jun K, Soichi K. A review of dental CAD/CAM: current status and future perspectives from 20 years of experience. Dental Materials Journal 2009: 28(1): 44-56. 2. Lee C, Alex T. CAD/CAM Dentistry: A new forum for dentist-technician Teamwork. Inside Dentistry, Sep 2006: vol 2, Issue 7. 3. Perng-Ru Liu. Panorama of Dental CAD/CAM Restorative systems. Compendium, July 2005: 26(7): 507-512. 4. Candice Z, Shermian A, Richard M, John D. Rapid prototyping technique for creating a radiation shield. J Prosth Dent, April 2007: 97(4): 236-41. 5. CAD/CAM: Principles, practice and manufacturing management. 2nd edition: Part-I. 6. Duret F, Blouin L. CAD/CAM in Dentistry. JADA 1988: 117: 715-20. 7. Rekow D. Computer aided design and manufacturing in dentistry: A review of the state of the art. J Prosth Dent 1987: 58(4):512-516. 8. Sebastian, Heike, Ralph. Direct mechanical data acquisition of dental impressions for the manufacturing of CAD/CAM restorations. J Dent 2007;35: 903-908. 9. Persson M, Andersson M, Bergman B. The accuracy of a high-precision digitizer for CAD/CAM of crowns. J Prosth Dent 1995; 74:223–9. 10. Persson A, Andersson M, Oden A, Sandborgh-Englund G. A three dimensional evaluation of a laser scanner and a touch-probe scanner. J Prosth Dent 2006;95:194–200.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411020EnglishN2018October26Life SciencesProtective Effects of Picrorhizakurroa  Against Fumonisin B1 Induced Hepatotoxicity in Mice   English2531K. KrupashreeEnglish P. RachithaEnglish G. V. JayashreeEnglish Farhath KhanumEnglishObjectives: The aim of the present study is to evaluate hepatoprotective effect of Picrorhizakurroaextracts (PKE) against Fumonisin b1 (Fb1) induced hepatotoxicity. Methods: Hepatoprotective analysis was done by estimating serum biochemical parameters Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), antioxidant enzyme status lipid peroxidations, ROS generation, and protein carbonyls were also estimated to know the oxidative damage. Further protein expressions were confirmed by western blotting. Results: The mice treated with 100 and 200 mg/kg b.wt PKE, showed a significant reduction in serum AST and ALT to 175.41 ± 7.82, 68.52±1.57 and 126.64 ± 1.72, 57.41±1.28 units/ml of serum respectively. The decrease in antioxidant levels with Fb1 was significantly restored with 100 and 200 mg/kg by wt PKE. The lipid peroxidation products with Fb1 treatment was also reduced with PKE supplementation. The Fb1 induced ROS was reduced with 60 and 140% by 100 and 200 mg/kg/ by wt PKE administration. The PKE restored CAT and GPx enzyme/protein levels and further down regulated caspase 8 and caspase 3 expression. Conclusion: The present observations suggested that the treatment with PKE extract enhance the recovery from Fb1 induced hepatic damage due to its antioxidant and hepatoprotective property. EnglishFumonisin b1, Picrorhizakurroa, Antioxidants, Oxidative stress, ApoptosisIntroduction Fumonisins are group of mycotoxins mainly produced from Fusariumverticillioides, Fusariummoniliforme is a common contaminants of corn and corn products throughout the world. The most potent and abundant of the class of fumonisins is fumonisin b1 (Fb1) which causes specific toxicological effects in humans and animals [1,2]. Fumonisin b1 causes equine leukoencephalomalacia in horse and porcine pulmonary edema in swine  [3,4], and it has been reported as hepatotoxic, nephrotoxic, and carcinogenic in animals and human [5]. In vivo studies demonstrated that fumonisin b1 also induced apoptosis and oxidative stress in kidney and liver [6,7]. Fb1 are known to affect sphingolipid metabolism by inhibiting the enzyme ceramide synthase. Inhibition of ceramide synthase causes apoptosis, accumulation of sphingoid bases (sphinganine and sphingosine) and decreases the ceramide [8,9]. Fb1 has been shown to disrupt lipid biosynthesis in vitro and in vivo in rat liver with changes occurring in the major cellular membrane phospholipids fractions and their fatty acid (FA) content by inducing the oxidative radicals such as superoxide anion and nitric oxide which are responsible for oxidative stress in the tissue [10]. Hence Fb1 is more toxic and abundant fumonisins causes liver damage in many animals [11]. PicrorhizakurroaRoyle ex Benth (P.kurroa) commonly called kutki a well-known Ayurvedic herb. Generally it has been used to treat liver toxicity and upper respiratory tract, and also to treat dyspepsia, scorpion sting and chronic diarrhea [12,13,14]. The P.kurroa contains chemical constituents like Apocynin, picrorhizoside, picroside-I, cinnamic acid, verminosidepicrogentioside, piscrocin, cucurbitacin, pikuroside, vanillic acid, picrosecoside –I [12,15,16]. P. kurroa has many medicinal benefits such as anti-allergic, anti-neoplastic immunomodulatory and anti-anaphylactic activities [12,17,18] The P.kurroa has been recently reported to inhibit arthritis through inhibition of pro-inflammatory cytokines and angiogenesis and which have protective effects against 2-acetylaminofluorene-induced hepatotoxicity in Wistar rats and non alcoholic fatty liver disease [19,20,21]. The active component Picroliv against Leishmaniadonovani infections in Mesocricetusauratus and hepatoprotective compound in mice [22,23,24]. The flavonoid apocynin is one of the active component of P. kurroa and has been noted to attenuate Parkinson&#39;s, ischemia-reperfusion and hypoxia by arresting NADH oxidase expression during oxidative stress.[12,25,26,27]. Hence the present study is to investigate the P. kurroa protective effects against Fb1 induced hepatotoxicity. Materials and methods Chemicals and reagents Fumonisin b1, 2, 7-dichloro-dihydrofluorescein diacetate (Sigma Bangalore), 2-nitrobenzoicacid (DTNB) Hi-Media (Bangalore, India). The other chemicals used were of high purity grade and were procured from Merck (Bangalore, India).  Plant material P. kurroa root material was purchased from the local market and identified by Dr. K. Madhava Chetty, Botanist, Department of Botany, Sri Venkateswara University, Tirupati, India. A voucher specimen (Herbarium Accession Number 801) was deposited in the herbarium, Department of Botany, S.V. University, Tirupati, India. Preparation of 70 % ethanolic fraction of P.kurroa(PKE) P. kurroa roots were washed thoroughly, shade dried and finely powdered. The 100g root powder was macerated with 70% ethanol in a shaker for 2 days. The extract was filtered using micropore membrane and concentrated using flash evaporator followed by lyophilization to remove the residual water. The yield of the extract was recorded as 25g. Experimental design Forty eight male Balb/c mice weighing 25g were selected from the stock colony, Defence Food Research Laboratory, Mysore, India. The animals were housed in acrylic fibre cages, temperature (25 ± 20C) and maintained in 12 h light/dark cycle. The mice were fed with a commercial pellet diet (Sri Venkateswara Enterprises, Bangalore, India) and water was provided ad libitum. The animal studies were conducted according to the guidelines from institute animal ethical committee for the purpose of the control and supervision of experiments on animals NO: 28/IAEC/CPCSEA. (I) Control group (II) PKE 200 mg/kg b/wt (body weight)   (III) Fb1 2.25mg/kg b/wt (IV) Fb1 2.25mg/kg b/wt + PKE 50mg/kg b/wt (V) Fb1 2.25mg/kg b/wt + PKE 100mg/kg b/wt (VI) Fb1 2.25mg/kg b/wt + PKE 200mg/kg b/wt. PKE was pretreated for 7 days oral administration. Fb1 2.25mg/kg b/wt was injected subcutaneously for 3 days. Controls mice were fed orally with an equal amount of saline. After the experiment mice were sacrificed, serum and liver tissues were collected for analysis. Bhandari et al., 2001 [28]. Serum biochemistry Estimation of ALT and AST  The serum biochemical markers such as ALT and AST were determined according to the kit suppliers protocols (Cat no. 11409003 and 11408002 Canada). Tissue biochemical parameters Estimation of hepatic antioxidant enzymes Liver tissues were homogenized in 50mM phosphate buffer saline (pH 7.4). The hepatic antioxidant enzymes such as SOD, GPx and GR were determined according to the protocols of kit supplier (Randox, Cat no. SD. 125, RS 504 and GR 2368, Canada). DTNB method was used to determine Glutathione content [29]. CAT enzyme content was estimated manually by spectrophotometric method [30]and the results were expressed in U/g tissue. Protein contents were determined by Bradford method (1976) [31] and the results were expressed as U/mg of protein. Estimation of hepatic lipid peroxidation Hepatic lipid peroxidation was determined by measuring the malondialdehyde according to Buege and Aust (1978) [32]. Liver tissues were homogenized in 2mL of phosphate buffer (pH 7.0). TCA (10%), 0.5mL and 2mL of TBA mixture were added to tissue homogenate (0.5mL). The TBA mixture contained TBA (0.35%), SDS (0.2%), FeCl3 (0.05mM) and BHT in glycine-HCl buffer (100mM, pH 3.6). The above reaction mixture was boiled at 1000C for 30 min. The mixture was centrifuged at 8000 rpm (Revolutions per minute) for 10min and the absorbance was measured at 532 nm and the results were expressed as moles/mg of protein. Estimation of ROS Fluorescent probe 2’, 7’- dichloro-dihydrofluoresceindiacetate was used to detect ROS generation in liver tissue by Wang and Joseph (1999) [33] method. To the liver fractions 40 µl of 1.25 mM 2’, 7’- dichlorfluorescein-diacetate and 142 µl methanol was added and the samples were incubated for 15 min at 370C. The fluorescence was measured at 485 nm excitation and 525 nm emission using Hidex plate chameleon TM 144 V (Finland). Western blot analysis The oxidative and apoptosis marker expression was analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting. The liver sample was homogenized with lysis buffer, pH 7.4 with protease inhibitor cocktail and total protein levels were estimated by the method of Bradford (1976) [31] The liver homogenate 50µg of proteins were separated on SDS-PAGE and transferred onto a nitrocellulose membrane using an electro blotting apparatus (Cleaver Scientific Ltd, UK). After transfer, the membranes were probed with primary antibodies against GAPDH (sc-5286) GPx (sc-22146), CAT (sc-34280), caspase 8 (sc-81657), caspase 3(sc-52746),(Santa Cruz Biotechnology, Santa Cruz, CA, USA, sigma) at 1:1,000 dilution and incubated at room temperature for 3 h. The membranes were then washed in TBST followed by incubation for 2 h at room temperature in dark with horseradish peroxidase (HRP) conjugated rabbit anti-goat, goat anti-mouse and goat anti-rabbit secondary antibodies (DAKO, Denmark) at 1:10,000 dilutions. The membranes were washed again and developed using a chemiluminescence detection system (ProteoQwest1, Sigma). Developed membranes were exposed to X-ray film and the developed band intensity was captured.  NIH image J software was used to measure the western blot band intensity. Statistical analysis The results were analyzed by one-way ANOVA followed by a Tukey’s HSD- post hoc test. Significance was set at 0.05 and all comparisons were made against the control group. Results P.kurroa regulates ALT and AST The hepatic function marker namely alanine aminotransferase (ALT), aspartate aminotransferase (AST) were estimated to diagnose the liver health. These enzymes were elevated in toxic or stress conditions due to the extracellular release particularly in liver. In the present study observed an increase in ALT and AST (p < 0.05) (Table. 1). However P. kurroa supplemented mice showed a dose dependent decrease in ALT and AST contents (p < 0.05) which indicates its protective effects against liver damage. Protective effect of P. kurroa against oxidative stress Antioxidant enzymes namely CAT, GPx, GR and GSH gets decreased when the liver undergo toxic condition induced by Fb1. In the present study observed decrease in antioxidant enzyme content in Fb1 challenged mice (p< 0.05). However a significant increase (p< 0.05) in antioxidant enzymes was observed with 100 and 200 mg/kg by wt P. kurroa supplementation. Whereas SOD was not affected by Fb1 treatment. (Table 2). P. kurroa inhibits lipid peroxidation Oxidative degradation of lipids caused by free radicals was measured by estimating malondialdehye content. The Fb1 treated liver showed the increase of malondialdehyde formation (P< 0.05), whereas P. kurroa supplemented mice decreased lipid peroxidation with 100 and 200mg/kg by wt PKE treatment (P< 0.05) which suggests that P. kurroa exerts protective effects against free radicals mediated lipid damage (Table 2). P. kurroa inhibits ROS generation The reactive oxygen species such as hydroxyl radical (HO•), superoxide anion (•O2−), and hydroxyl anion (HO−) trigger the cellular damage by oxidizing the biomolecules therefore estimation of ROS is essential to study the oxidative stress. The ROS estimation was carried out using fluorescent probe DCFH2DA. Here we observed 264% increases (p < 0.05) in fluorescence in Fb1 treated liver homogenates. The pre-treatment of PKE decreased 92 to 165% (p < 0.05) of ROS generation respectively (Fig. 1(A)). Protective effects of P. kurroa on oxidative stress and apoptotic biomarker The effect of P. kurroa against Fb1 stress was further evaluated by western blotting. The key enzymes of oxidative stress such as GPx, CAT and GAPDH and apoptotic enzymes caspase 3 and caspase 8 was evaluated (Fig. 3). The antioxidant biomarkers GPx and CAT were down-regulated with Fb1 treatment and caspase 8, caspase 3 were increased in the expression. Whereas P.kurroa pretreatment significantly restored the GPx, CAT expression and down regulated the apoptotic enzymes caspase3, caspase 8 protein expression. Discussion Fumonisin b1 are secondary metabolites of fungi which are associated with many disorders in animals and humans and also responsible for apoptosis and oxidative stress. Protective effect of herbal extracts against fumonisin b1 induced toxicity has fewer reports. El-Adawi et al. (2011) [34] studied protective effects of milk thistle and grape seed extracts on fumonisin B1 induced hepato- and nephro-toxicity in rats and Sozmen et al. (2014) [35] reported protective effects of sylimarin against fumonisin B1-induced hepatotoxicity in mice.P. kurroa is a well-known ayurvedic herb and shown hepatoprotective activity in diverse models of liver toxicity. Hence the present study investigated the hepatoprotective effects induced by fumonisin b1 induced toxicity. AST and ALT are enzymes that catalyze the transfer of α-amino groups from aspartate and alanine to the α-keto group of ketoglutaric acid to generate oxalacetic and pyruvic acids respectively when the liver is in toxic or stress condition, therefore serum concentrations of aminotransferases level increase. Several reports show that plants and phytochemicals attenuate the aminotransferases level [36]. The pretreatment of animals with the extracts P.kurroa resulted to a significant and dose dependent decrease in the levels of ALT and AST. Enzymes such as superoxide dismutases (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione (GSH) have been proposed as biomarkers of oxidative stress and toxic effect of tissue. CAT is well known antioxidant enzyme which detoxifies the hydrogen peroxide without electron donor and GPx also metabolize H2O2 to non-toxic products [37]. The GSH plays a fundamental role in cellular metabolism which provides the defence against reactive oxygen species and other toxic radicals and the GR is responsible for generation of GSH. In the present study we observed a decrease concentration of these antioxidant enzymes and the pretreatment of  P. kurroa showed a recovery in the activity of these enzymes several reports also demonstrated that supplementation of herbal extracts can increases that antioxidant level induced by other toxic radicals. The lipid peroxidation involves the mechanism formation or propagation of lipid radicals by up taking the oxygen and rearrangement of the double bonds in unsaturated lipids and the eventual destruction of membrane lipids and final products breaks downs including ketones, alkanes, aldehydes and ethers [38]. This lipid peroxidation was measured by malondialdehyde in the present study the malondialdehyde level was increased in the Fb1 treated group and it was minimized by P. kurroa pretreated group. Western blot is used to separate and identify proteins separated based on molecular weight. The house keeping gene glyceraldehyde 3-phosphate dehydrogenase (GAPDH) used as reference proteins to normalize the target protein during the protein targeting. Therefore, to accurately compare western blotting signals, one must compensate for these non-sample-related variations in signal intensity so GAPDH increasing expression shows that the house keeping proteins are subject to change in many biological conditions, such as toxic condition and some diseases [39]. The antioxidant marker proteins CAT and GPx already demonstrated that in biochemical parameters the enzyme activity decreased in oxidative stress condition. In the western blotting also the expression of GPx and CAT down regulated with Fb1 whereas pretreatment of P. kurroa significantly restored the enzyme. Increasing the antioxidant able to accelerate the removal of the reactive oxygen species so which may the reason for increasing the GPx, CAT in the present study. Fb1 treatment activates enzyme Caspase-8, Caspase-8 is signalling molecule involved in TNF tumor necrosis factor-alpha apoptotic pathway plays a pivotal role in Fb1-induced apoptosis [26]. In the present study we observed up regulation of Caspase-8 and Caspase-3 whereas P. kurroa pretreated with 200mg down regulates the expression of apoptotic enzymes. P. kurroa seems to be a promising herb to protect Fb1 induced hepatotoxicity. The extract was found to prevent lipid oxidation and also to increase the activity of the antioxidant enzymes apart from down regulating the caspases. Hence with the protein expression studies P. kurroa showed the protective effect against Fb1 induced hepatotoxicity. Conclusion Fb1 associated with hepatotoxic effect and induction of oxidative stress. Modulating roles against ROS mediated damage for cell survival by nutrition supplement is therefore of interest. Present study evaluated the modulating properties of P. kurroa against oxidative stress and apoptosis mediated by Fb1. There inhibitory effects might be due to enriched active ingredients present in P. kurroa. Further molecular and analytical studies are necessary to understand the concealed mechanism of action of the P. kurroa extract and also for the usage as therapeutic agent. 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: None Source of funding: None Fig. 1 Effect of PKE on hepatic ROS generation. Mice were treated with different doses of PKE followed by Fb1 and the liver ROS generation was measured using spectrofluorimeter (n= 8, P < 0.05, significantly different from the control group and homogenous sub groups share common letter (a= P< 0.05 versus Fb1 treated group and b= P< 0.05 versus control group)). Fig.2. The protective effect of pre-treatment of PKE on Fb1 induced expression of oxidative stress marker proteins CAT, GPx and apoptosis marker proteins caspases-8, caspase-3 analysed by western blotting (B,C,D,E). The band intensity is calculated by Image-J software. The data are represented as mean ± SD of three independent experiments. #PEnglishhttp://ijcrr.com/abstract.php?article_id=2539http://ijcrr.com/article_html.php?did=2539 Ismaiel A, Papenbrock J. Mycotoxins: producing fungi and mechanisms of phytotoxicity. Agriculture. 2015;5:492-537. Marschik S, Hepperle J, Lauber U, Schnaufer R, Maier S, Kühn C, Schwab-Bohnert G. Extracting fumonisins from maize: efficiency of different extraction solvents in multi-mycotoxin analytics. Mycotoxin research. 2013;29:119-29. Marasas WF, Kellerman TS, Gelderblom WC, Thiel PG, Van der Lugt JJ, Coetzer JA. Leukoencephalomalacia in a horse induced by fumonisin B? isolated from Fusarium moniliforme.1988. Bacelar RG, das Chagas Cardoso Filho F, de Abreu Costa J, Costa AP, N & Obrega MM, Muratori MC. Fusarium spp. and fumonisin in feed for equine and its importance for occurrence of leukoencephalomalacia. African Journal of Microbiology Research. 2016;32:1248-56. Dall&#39;Asta C, Vedani P, Manunta P, Pizzocri P, Marchi M, Paganelli M, Folli F, Pontiroli AE. Effect of weight loss through laparoscopic gastric banding on blood pressure, plasma renin activity and aldosterone levels in morbid obesity. Nutrition, Metabolism and Cardiovascular Diseases. 2009;2:110-4. Sharma RP, Dugyala RR, Voss KA. Demonstration of in-situ apoptosis in mouse liver and kidney after short-term repeated exposure to fumonisin B1. Journal of comparative pathology. 1997; 4:371-81. Abbes S, Ben Salah-Abbès J, Jebali R, Younes RB, Oueslati R. Interaction of aflatoxin B1 and fumonisin B1 in mice causes immunotoxicity and oxidative stress: Possible protective role using lactic acid bacteria. Journal of immunotoxicology. 2016;1:46-54. Zitomer NC, Mitchell T, Voss KA, Bondy GS, Pruett ST, Garnier-Amblard EC, Liebeskind LS, Park H, Wang E, Sullards MC, Merrill AH. Ceramide synthase inhibition by fumonisin B1 causes accumulation of 1-deoxysphinganine a novel category of bioactive 1-deoxysphingoid bases and 1-deoxydihydroceramides biosynthesized by mammalian cell lines and animals. Journal of Biological Chemistry. 2009;8:4786-95. Soriano JM, Gonzalez L, Catala AI. Mechanism of action of sphingolipids and their metabolites in the toxicity of fumonisin B1. Progress in lipid research. 2005;6:345-56. Abel S, Gelderblom WC. Oxidative damage and fumonisin B1-induced toxicity in primary rat hepatocytes and rat liver in vivo. Toxicology. 1998;(2-3):121-31. Voss KA, Riley RT, Bacon CW, Chamberlain WJ, Norred WP. Subchronic toxic effects of Fusariummoniliforme and fumonisin B1 in rats and mice. Natural toxins. 1996;1:16-23. Krupashree K, Kumar KH, Rachitha P, Jayashree GV, Khanum F. Chemical composition, antioxidant and macromolecule damage protective effects of Picrorhizakurroa Royle ex Benth. South African Journal of Botany. 2014;94:249-54. Vivekanandan P, Gobianand K, Priya S, Vijayalakshmi P, Karthikeyan S. Protective effect of picroliv against hydrazine-induced hyperlipidemia and hepatic steatosis in rats. Drug and chemical toxicology. 2007;3:241-52. Banerjee D, Maity B, Nag SK, Bandyopadhyay SK, Chattopadhyay S. Healing Potential of Picrorhiza kurroa (Scrofulariaceae) rhizomes against indomethacin-induced gastric ulceration: a mechanistic exploration. BMC complementary and alternative medicine. 2008;1:3. Upadhyay D, Dash RP, Anandjiwala S, Nivsarkar M. Comparative pharmacokinetic profiles of picrosides I and II from kutkin, Picrorhizakurroa extract and its formulation in rats. Fitoterapia. 2013;85:76-83. Rahman S, Sultana S. Protective effects of Picorrhizakurroa extract against 2-acetylaminofluorene-induced hepatotoxicity in Wistar rats. Journal of Environmental Pathology, Toxicology and Oncology. 2007;26(3). Bhandari P, Kumar N, Singh B, Kaul VK. Simultaneous determination of sugars and picrosides in Picrorhiza species using ultrasonic extraction and high-performance liquid chromatography with evaporative light scattering detection. Journal of Chromatography A. 2008;2:257-61. Rajkumar V, Guha G, Kumar RA. Antioxidant and anti-neoplastic activities of Picrorhizakurroa extracts. Food and Chemical Toxicology. 2011;2:363-9. Shetty SN, Mengi S, Vaidya R, Vaidya AD. A study of standardized extracts of Picrorhizakurroa Royle ex Benth in experimental nonalcoholic fatty liver disease. Journal of Ayurveda and integrative medicine. 2010;3:203. Kumar R, Gupta YK, Singh S, Arunraja S. Picrorhizakurroa Inhibits Experimental Arthritis Through Inhibition of Pro?inflammatory Cytokines, Angiogenesis and MMPs. Phytotherapy research. 2016;1:112-9. Philippens IH, Wubben JA, Finsen B, A‘t Hart B. Oral treatment with the NADPH oxidase antagonist apocynin mitigates clinical and pathological features of parkinsonism in the MPTP marmoset model. Journal of Neuroimmune Pharmacology. 2013;3:715-26. Mittal N, Gupta N, Saksena S, Goyal N, Roy U, Rastogi AK. Protective effect of Picroliv from Picrorhizakurroa against Leishmaniadonovani infections in Mesocricetusauratus. Life sciences. 1998;20:1823-34. Girish C, Pradhan SC. Hepatoprotective activities of picroliv, curcumin, and ellagic acid compared to silymarin on carbon-tetrachloride-induced liver toxicity in mice. Journal of pharmacology & pharmacotherapeutics. 2012;3:149. Mallick M, Singh M, Parveen R, Khan W, Ahmad S, ZeeshanNajm M, Husain SA. HPTLC analysis of bioactivity guided anticancer enriched fraction of hydroalcoholic extract of Picrorhizakurroa. BioMed research international. 2015;2015. Wang Q, Tompkins KD, Simonyi A, Korthuis RJ, Sun AY, Sun GY. Apocynin protects against global cerebral ischemia–reperfusion-induced oxidative stress and injury in the gerbil hippocampus. Brain research. 2006;1:182-9. Philippens IH, Wubben JA, Finsen B, A‘t Hart B. Oral treatment with the NADPH oxidase antagonist apocynin mitigates clinical and pathological features of parkinsonism in the MPTP marmoset model. Journal of Neuroimmune Pharmacology. 2013;3:715-26. Hui-guo L, Kui L, Yan-ning Z, Yong-jian X. Apocynin attenuate spatial learning deficits and oxidative responses to intermittent hypoxia. Sleep medicine. 2010;2:205-12. Bhandari N, He Q, Sharma RP. Gender-related differences in subacute fumonisin B1 hepatotoxicity in BALB/c mice. Toxicology. 2001;(2-3):195-204. Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman&#39;s reagent. Analytical biochemistry. 1968;25:192-205. Cohen G, Dembiec D, Marcus J. Measurement of catalase activity in tissue extracts. Analytical biochemistry. 1970;1:30-8. M.M. Bradford. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding, Anal. Biochem. 72 (1976 ) 248-54. J.A. Buege, S.D. Aust. Microsomal lipid peroxidation, Methods. Enzymol.  52 (1978) 302-10. Wang H, Joseph JA. Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader1. Free Radical Biology and Medicine. 1999;(5-6):612-6. El-Adawi H, El-Azhary D, El-Shafeey M, Abdel-Mohsen M. Protective effect of milk thistle and grape seed extracts on fumonisin B1 induced Hepato-and nephro-toxicity in rats. Journal of Medicinal Plants Research. 2011;27:6316-27. Sozmen M, Devrim AK, Tunca R, Bayezit M, Dag S, Essiz D. Protective effects of silymarin on fumonisin B1-induced hepatotoxicity in mice. Journal of veterinary science. 2014;1:51-60. Agbafor KN, Ogbanshi ME, Akubugwo EI. Phytochemical screening, hepatoprotective and antioxidant effects of leaf extracts of Zapotecaportoricensis. Advances in Biological Chemistry. 2014;1:35. Radovanovi? TB, Borkovi?-Miti? SS, Perendija BR, Despotovi? SG, Pavlovi? SZ, Caki? PD, Sai?i? ZS. Superoxide dismutase and catalase activities in the liver and muscle of barbel (Barbusbarbus) and its intestinal parasite (Pomphoryinchuslaevis) from the Danube river, Serbia. Archives of Biological Sciences. 2010;1:97-105. Repetto M, Semprine J, Boveris A. Lipid peroxidation: chemical mechanism, biological implications and analytical determination. In Lipid peroxidation 2012. In Tech. Li R, Shen Y. An old method facing a new challenge: re-visiting housekeeping proteins as internal reference control for neuroscience research. Life sciences. 2013;13:747-51.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-52411020EnglishN2018October26Life SciencesDiversity of the Family Leguminosae in Koch Bihar District, West Bengal   English3241Subhajit Bandyopadhyay EnglishIntroduction: Legume - a fascinating group of flowering plants belongs to the family Leguminosae or Fabaceae is deserve special attention as they play vital role both in human welfare as well as in ecological aspect. The district of Koch Bihar of West Bengal state has no account about the diversity of leguminous plants and their utilization by the ethnic and local peoples which initiates to undertake the present work. Methods: Extensive field surveys in different parts of Koch Bihar in different seasons of five consecutive years were conducted to record the legumes of the district and their uses following the standard methods. Voucher specimens were processed and identified by using relevant literature and matching with herbarium specimens. Result and Discussion: It is evident from the present study that the legumes of Koch Bihar district are represented by 81 species under 36 genera with Desmodium as dominant genus having 9 species. Maximum number of species have been recorded in the subfamily Faboideae (47 species) followed by Caesalpinioideae(18 species) and Mimosoideae(16 species).  Among the 81 species of legumes there are 29 species of herbs, 28 species of trees, 16species of shrubs and 8species of climbers. It is interesting to note that a good number of legumes are exotic in origin and American elements are more dominant among the alien species. During the field study utilization of legume by the major ethnic communities (viz. Kheria, Oraon, Rabha, Rajbanshi, and Santal) and the local inhabitants of the district have also been recorded.  It reveals that 31 species under 24 genera which is about 38% of the legume flora of the district are used in various purposes and several species have more than one kind of use. Conclusions: Destruction of the habitat and the anthropogenic interferences are identified as the basic causes for the loss of diversity of legumes of the district. Similarly, acculturation   is the reason for extinction of traditional knowledge regarding herbal therapy.  EnglishMimosoideae, Caesalpinioideae, Faboideae, Ethnic community, Traditional knowledgeINTRODUCTION   The family Leguminosae (Fabaceae) commonly known as legume or bean family is the third largest family among the flowering plants which is represented by 19,500 species under 770 genera1 and is cosmopolitan in distribution. Human society is benefited by this group of plants as they are not only the source of pulses, fodder, oil seeds, medicines, timber etc but they also increase soil fertility by fixing atmospheric Nitrogen. This family is traditionally divided into three sub-families namely Mimosoideae, Caesalpinioideae and Faboideae (=Papilionoideae). Hutchinson2 had recognized these three sub-families as independent families-Mimosaceae, Caesalpiniaceae and Fabaceae. This view was followed by Cronquist3, Dahlgren4 and others. But the present trend is to consider the above stated three sub-families under broadly circumscribed Leguminosae or Fabaceae. Morphological characters as well as rbcL sequence data support this view5. Takhtajan6, Thorne7 and APGIV8 also recognized the similar treatment. Recently the Legume Phylogeny Working Group9 based on plastid matK gene sequences subdivided Leguminosae into six subfamilies namely Caecalpinioideae (recircumscribed), Cercidoideae, Detarioideae, Dialioideae, Duparquetioideae and Papilionoideae.    Koch Bihar- a district of North eastern part of the state of West Bengal is floristically rich. Though a number of stray publications are existing regarding the flora of the Koch Bihar like Aditya and Ghosh10, Bandyopadhyay11, Bandyopadhyay and Mukherjee 12,13,14, Banerjee15 but none of them reflect the diversity of leguminous plants of the district. The present work is therefore, undertaken to record the species diversity of the legumes of Koch Bihar district of West Bengal. Not only that an endeavor has also been made to record the local uses of such leguminous plants by the local ethnic and rural peoples of the district which will be helpful to preserve the indigenous knowledge of the ethnic communities of the district.   The district of Koch Bihar is situated under Jalpaiguri division of the state of West Bengal in between 26o 32’46”to 25o57’57”N latitude and 89o 52’ 00”to 88o45’02” E longitude and covering an area of 3,386 sq Km. The district is surrounded by Alipurduar district of West Bengal in northern and most part of Western side. The Southern boundary of the district is very much indented and is formed by the Rangpur district of Bangladesh. The eastern boundary is formed by the Goalpara district of Assam. The entire district is intersected by six river systems, namely Tista system, Jaldhaka system, Torsha system, Kalzani system, Raidak system and Gadadhar system. The soil of Koch Bihar district is alluvial type of rather recent origin and is mainly sandy loam type. The climate of the district is characterized by high humid atmosphere and abundant rain with the temperature being seldom excessive. The district receives an average rainfall of 320.1cm. Rajbanshi is the major ethnic community which constitute about 40% population of the district. The other ethnic groups are Kheria, Oraon, Rabha and Santal. Most of them are village dwellers and depend on plant and plant products to maintain their life and livelihood. MATERIALS AND METHODS   The present work is based on screening of herbarium specimens deposited at Central National Herbarium, Howrah and extensive survey conducted in different areas of Koch Bihar district in different seasons of five consecutive years. Plant specimens were collected from the field and preserved following the guidelines of Lawrence16 and Jain & Rao17. Local uses of the plants and vernacular names (if any) were procured from the ethnic medicine men and elderly knowledgeable persons of the villages through interview. The information was collected following Jain18, 19, 20 and Pal & Jain21 with some minor changes wherever required. Correct identity and updated nomenclature of the collected plant specimens were established with the help of published literature and also comparing with the authentic herbarium specimens of Central National Herbarium (CAL). RESULTS   Species diversity in the three sub-families of Leguminosae viz Faboideae (=Papilionoideae). Caesalpinioideae and Mimosoideae are presented in table 1, 2 and 3 respectively. Updated nomenclature of each species along with vernacular name (if any), habit, flowering and fruiting periods and their distributional status have been provided in these tables. Uses of plants by the ethnic communities and rural peoples have also been provided in the column ethno botanical uses. The following abbreviations are used in the table: rt.-root, tw.-twig, lf.-leaf, fl.-flower, fr.-fruit, sd.-seed, wd.-wood, pl.-plant, st. bk. - stem bark DISCUSSION   The forest vegetation of Koch Bihar district is Tropical moist deciduous type. Presently the district has a total forest cover of 45.31 sq. km and the forests are scattered in few pockets as protected forests. The common trees and shrubs of legumes in forest terrain includes Acacia catechu, Albizia chinensis, ,Butea monosperma, Dalbergia sisoo, Desmodium pulchellum, Erythrina stricta ,Flemingia macrophylla, Flemingia strobilifera etc. A number of herbaceous species of legumes are also grown in the forest floor. Some of them are Crotalaria albida, Crotalaria bialata, Desmodium motorium, Desmodium triquetrum, Mimosa pudica, Senna alata, Vicia hirsuta,Vicia tetrasperma etc. The common climbers and twiners found in this forest are Abrus precatorius, Caesalpinia bonduc, Caesalpinia cucullata, Cajanus scarabaeoides, Mucuna pruriens and Pueraria phaseoloides.   Beside the forest terrain, a vast stretches of land in the villages and urbanized area as well as wastelands beside agricultural fields, roadsides, railway tracks, canal banks, harbor a number of leguminous species. Tree legumes are generally planted by the villagers for meeting their needs or planted in afforestation programme by the forest department beside roads and waste places. It has been seen those tree species are sometimes naturalized and running wild. Some of them are Acacia auriculiformis, Acacia farnesiana, , Acacia nilotica subspecies cupressiformis, Albizia lebbeck,  Albizia lucidior, Cassia fistula,, Dalbergia sisoo, Delonix regia, Derris indica,, Erythrina stricta, Erythrina variegata, Leucaena latisiliqua, Peltophorum pterocarpum, Pithecellobium dulce,  Samanea saman, Senna siamea , Sesbania grandiflora, Tamarindus indica and others. The common herbs and undershrubs of those areas are Alysicarpus monilifer, Alysicarpus vaginalis, Crotalaria pallida, Desmodium gangeticum, Desmodium laxiflorum, Desmodium triflorum, Medicago lupulina, Mimosa pudica, Senna occidentalis, Senna sophera,Senna tora and many others.    It has been noted during study that a good number of species are exotic in origin and they became naturalized in Koch Bihar flora. American elements are more dominant among the exotic species, some of them are Acacia farnesiana, Caesalpinia pulcherrima, Clitoria ternatea , Delonix regia, Leucaena latisiliqua, Mimosa pudica, Pithecellobium dulce, Samanea saman, Senna alata, Senna occidentalis, Senna sophera, Senna tora and others. Similarly Lens culinaris, Lathyrus aphaca, Medicago lupulina, Melilotus alba, Vicia hirsuta, Vicia sativa etc constitute the European elements of the flora. Legumes of African origin naturalized in this district include Acacia nilotica, Lathyrus sativus, Sesbania sesban and Tamarindus indica.   The present study reveals that the legumes of the district of Koch Bihar are represented by 81 species under 36 genera. The proportions of genera to species are 1: 2.25. The numerical representation of genus and species under three subfamilies is presented in Table 4 and Diagram 1. A comparison between Koch Bihar, West Bengal22 and India23 regarding diversity of Legumes has been presented in Diagram 2. There are 28 species of trees, 16 species of shrubs, 29 species of herbs and 8 species of climbers recorded during study. The analysis of habits of the species in each sub-family is provided in Table 5 and Diagram 3. Among the legumes Desmodium shows maximum species diversity having 9species followed by Acacia, Crotalaria and Senna with 6 species each. In contrary there are 16 genera having single species each.   During the present study uses of leguminous plants by the ethnic communities and rural peoples of the district has also been recorded. The results shows that 31 species of legumes under 24 genera are used for various purposes which are about 38% of the legume flora of the district and several species have more than one kind of uses. The collected information shows that plants and plant parts of 11 species are edible, 20 species have medicinal uses, 2 species are used as fodder, woods of 3 species are used in constructions and making household articles and 6 species have miscellaneous uses. A total of 69 uses have been recorded during the present study and it has been noted that leaves of the legumes are used in maximum occasion (18) followed by stem & twigs (14) and roots & seeds (09).   CONCLUSION The present study concludes that the Leguminosae or Fabaceae is the most dominant and diversified family which constitutes about 10% of the total Angiospermic flora of the district. But the rapid urbanization and increase in population causes serious damage to the habitats of these plants. Much damage to the forest vegetation is being done by the cattle grazing. Grazing animals on one hand browse the tree seedlings and on the other hand trampling the soil and seedlings.  Therefore, soil become compact and become unsuitable for the growth of the plants. Anthropogenic interference like extraction of “catechu” gum from Acacia catechu, peeling of barks for preparation of medicines and careless and illegal cutting and lopping from the plants for the purpose of fodder and firewood are the causes of the loss of species diversity. Similarly, extensive collection of useful seeds, fruits, roots etc. from plants like –Abrus precatorius, Derris indica, Butea monosperma, Mucuna pruriens etc. effects the natural regeneration of population of the species. On the other hand the indigenous knowledge especially the uses of the herbal drugs are in threat due to modernization of the society and loss of interest among the young generation of ethnic and rural peoples about the traditional healing methods. It is, therefore, an urgent need to protect the plants to save the diversity of leguminous flora as well as the ethnic culture of the district. ACKNOWLEDGEMENT The author is thankful to the Director and Late Dr. V. Mudgal, Additional Director, Botanical Survey of India for providing institutional facilities during the work. Thanks are also due to all forest officers and staffs, ethnic practitioners and other resource persons of Koch Bihar district without whose active co-operation the work could not be accomplished. Author is also grateful to his teachers Late Prof. A.K. Sarkar, Prof. G.G. Maity and Prof. S.K. Mukherjee (Retd.) Department of Botany, University of  Kalyani for their valuable suggestions and encouragement during the work. Author acknowledges the immense help received from the scholars whose articles are cited and included in reference in the manuscript. The author is 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. Englishhttp://ijcrr.com/abstract.php?article_id=2540http://ijcrr.com/article_html.php?did=2540 The Legume Phylogeny Working Group. Legume phylogeny and classification in the 21st century: progress, prospects and lessons for other species rich clades. Taxon 2013; 62:217-48. Hutchinson J. The Families of Flowering Plants. 3rd ed. London: Oxford University Press; 1973. Cronquist A. Evolution and Classification of Flowering Plants. 2nded. New York: New York Botanic Garden; 1988. Dahlgren G. The last Dahlgrenogram. Systems of classification of dicotyledons. In : Tan K. editor. The Davis and Hedge Festschrift. Edinburgh: Edinburgh University Press; 1989.p.249-60. Doyle JA, Endress PK. Morphological phylogenetic analysis of basal angiosperms: comparison and combination with molecular data. Int Jour Plant Sci 2000; 165(6 suppl):S55-67. Takhtajan A. Flowering Plants. 2nd ed.Springer;2009 Thorne RF. (2003). An updated classification of the class Angiospermae   www.rsabg.org/publication/angiosp.htm. The Angiosperm Phylogeny Group.  An update of the Angiosperm Phylogeny Group classi?cation for the orders and families of ?owering plants: APG IV. Bot Jour Linn Soc 2016; 181: 1–20. The Legume Phylogeny Working Group. A new subfamily classification of the Leguminosae based on a taxonomically comprehensive phylogeny. Taxon 2017; 64:44-77. Aditya NR Ghosh RB.  Further contribution to the flora of Cooch Behar district, West Bengal.Jour Econ Tax Bot 1989; 13: 437-53. Bandyopadhyay S. A Systematic Census on the Sedges of Koch Bihar district, West Bengal. Ind Jour Appl Pure Biol 2017; 32:181-188. Bandyopadhyay S, Mukherjee SK.  Diversity of Aquatic & Wetland vascular plants of Koch Bihar district, West Bengal. In: Pandey AK et al., editors. Plant Taxonomy: Advances and Relevance. New Delhi: CBS Publishers; 2005.p.223-44. Bandyopadhyay S, Mukherjee SK.  Diversity of climbing plants in Koch Bihar district of West Bengal, India 2010; Pleione 4: 82-9. Bandyopadhyay S, Mukherjee SK.  A Sketch of the Monocot Flora of Koch Bihar district, West Bengal Jour Econ Tax Bot 2017; 40:99-103. Banerjee BC. Addition to the flora of Cooch Behar district, West Bengal. Jour Econ Tax Bot 1992; 16 :177-83 Lawrence GHM. Taxonomy of vascular plants. London: Macmillan Company; 1951. Jain SK Rao RR. A Handbook of Field & Herbarium Methods. New Delhi: Today and Tomorrows’ Printers and Publishers; 1977. Jain SK. Medicinal Plant lore of tribal of Bastar. Econ Bot 1965;  19:236-50 Jain SK. editor. Glimpses of Indian Ethnobotany. New Delhi: Oxford and IBH Publishing Company; 1981. Jain SK, A Manual of Ethnobotany, 2nd ed. Jodhpur: Scientific Publisher; 1995. Pal DC, Jain SK. Tribal Medicine. Calcutta: Naya Prakash ; 1999. Mitra S. Floristic diversity of West Bengal, India. Germany: Lambert Academic Publishing; 2016. Karthikeyan  S. 2000. A statistical analysis of flowering plants of India. In:  Singh NP, Singh DK, Hajra PK, Sharma BD. editors. Flora of India Intro. Vol., Part II. Calcutta: Botanical survey of India; p. 201 – 17.