Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524132EnglishN-0001November30HealthcareSUSTAINED INTRANASAL DRUG DELIVARY SYSTEM FOR THE TREATMENT OF GASTROPARESIS English0412Agrawal V.A.English Rajurkar R.MEnglish Mahle A.MEnglish Thonte S.S.EnglishThe present investigation concerns about the development of the colloidal dispersion of mucoadhesive polymers containing Domperidone for intranasal delivery. Colloidal dispersion was prepared by sonication method and was characterized. Methylcellulose, Hydroxypropyl methylcellulose and Chitosan were used as a release retardant material. The nasal isotonic buffer was prepared after calculating the Sodium chloride displacement (E value) of the ingredients and was used as a vehicle. E values were calculated from L iso values. The effects of HPMC and Chitosan on drug release profile were investigated. In the study it was found that HPMC has synergistic effect on viscosity and bioadhesive strength when used in combination with methyl cellulose. Formulations were evaluated for in vitro drug release profile, Appearance, pH examination, Drug content estimation In-vitro Bioadhesion studies at different contact times, for selection of the best batch. Formulation batch F2 was the optimized and was further studied for Histopathological examination and accelerated stability. EnglishColloidal dispersion, nasal isotonic buffer, E value, bioadhesion.INTRODUCTIONThe idea of bioadhesive polymers to prolong the contact time in the mucosal routes of drug delivery was introduced in the early 1980s and since it has attracted considerable attention by many pharmaceutical scientists. The potential of a drug delivery system to localize a drug at the site of absorption for an extended period and to promote intimate contact between the formulation and the underlying absorbing tissue has a great appeal for both local and systemic effects.1 Mucoadhesive dosage forms have some distinct advantages over conventional dosage forms. This prolongs residential time of dosage forms at the site of application and absorption to permit once or twice a day dosing, localize formulation on mucosa thereby providing a better chance for drug to be absorbed, reduce post nasal drip into the back of the throat and therefore minimize any bad taste problems and loss of drug formulation from nasal cavity, reduces anterior leakage of or drug out of nasal cavity, decrease mucocilliary clearance2 . Gastroparesis the term implies that gastric emptying is delayed in the absence of mechanical obstruction. Gastroparesis3 , also called delayed gastric emptying, is a medical condition consisting of a paresis (partial paralysis) of the stomach, resulting in food remaining in the stomach for a longer period of time than normal. Mucoadhesive colloidal dispersion is a very recent type of formulation for the delivery of insoluble drugs via nasal route. These are the formulations containg single or combination of synthetic, natural or combination of both types of Mucoadhesive polymers in the form of colloidal dispersion prepared by sonication. Generally these are prepared for insoluble drugs when the suspension form of the same drug has less nasal permeation. Domperidone4 is a D2 antagonist, chemically related to Haloperidol, but pharmacologically related to Metoclopramide. Belongs to the class of propulsive i.e. prokinetics. It is a potent antiemetic, antimigraine drug effective for preventing different kinds of emesis and used in gastroparesis. Its conventional dosage form such as tablet and suspension give poor bioavailability (15 to 18%) due to extensive first pass effect, whereas on rapid i.v. injection it has been shown to cause cardiac arrhythmias. Thus to increase its bioavailability (by changing route of administration) and patient compliance Mucoadhesive colloidal dispersion5 was This type of formulation can also solve the problems of conventional nasal drops and water insoluble drugs. AIM AND OBJECTIVE The present study was aimed towards preparation of Mucoadhesive colloidal dispersion for intranasal drug delivery which deliver drug in controlled manner and provide a practical, noninvasive and simple method to deliver therapeutic agent. The study was also aimed towards developing such a formulation which improves drug’s solubility characteristics and increases its bioavailability by avoiding First pass effect and gut wall metabolism. The objective of present work was to formulate nasal colloidal dispersion that can prolong contact time with nasal mucosa by mucoadhesion. Avoid First pass effect, reduce dose and dosing frequency by controlling release of drug to evaluate for Bioadhesive strength and Quality control of the preparation. MATERIALS AND METHODS Materials -Domperidone was obtained as a gift sample from Ajanta Pharmaceuticals Ltd Mumbai, Methylcellulose A4 M, HPMC K 4 M from ColorconAsia Pvt, Ltd, Goa, Chitosan, Polyethylene glycol 600, Benzalkonium chloride, Sodium chloride and Sodium metabisulphite from Loba chem. Pvt.Ltd.Mumbai, Sodium dihydrogen phosphate and Disodium hydrogen phosphate from Research lab fine chem. Mumbai. Nasal Mucosa was obtained from local slaughter house. Methods: Preparation of Standard Curve of Domperidone- Calibration curve for Domperidone in 10% methanolic phosphate buffer of pH 6.4 was prepared. Absorbance was measured using UV visible spectrophotometer (UV 1700Shimadzu) at λ max 284 nm. The graph of absorbance v/s concentration was plotted. Method of preparation of formulation batches5 : vehicle- Based on the Isotonisity calculation, the amount of NaCl required was found out and Nasal isotonic buffer solution of pH 6.5 was prepared. Polymer phase- The required quantity of polymers was taken and added slowly in 50 ml of vehicle with continuous stirring i mechanical stirrer at 1200 rpm for one hour. It was allowed to swell and hydrate. It was then kept in sonicator for 15 min at 30MHz/sec. to remove any fluff from it. Drug phase- Required quantity of drug and PEG 600 was taken in a glass bottle and 40ml of vehicle was added to it. It was sonicated at 30 MHz/sec. for about 2 hrs. It gives the dispersion of very fine particle size and improved solubility. Mixing of polymer phase with drug phase- The drug phase was added drop wise to the polymer phase udder continuous stirring using magnetic stirrer and mixed for half an hour .The volume was made to 100 ml with vehicle. Evaluation of formulations : Appearance: 6 The developed formulation batches were inspected visually. The observations are shown in table no.2. pH and Density of Mucoadhesive Colloidal Dispersion:7 The pH of each formulation batch was determined by using digital pH meter which was first calibrated by using phosphate buffers of ph 7 and 4. The Density was determined by using specific gravity bottle. The observations are shown in table no2. Drug content8 :From each formulation 0.1 ml (equivalent to 2mg) was taken in 100 capacity volumetric flask and diluted with methanolic phosphate buffer pH6.4 up to 100 ml shaken to dissolve. The content of the drug was estimated spectrophotometrically by using standard curve plotted at 284 nm. The observations are shown in table no.3 0.1 ml (equivalent to 2mg) was taken in 100 capacity volumetric flask and diluted with methanolic phosphate buffer pH6.4 up to 100 ml shaken to dissolve. The content of the drug was estimated spectrophotometrically by using standard curve plotted at 284 nm. The observations are shown in table no.3. Viscosity measurements -51, 52, 53The viscosities of all the formulations were determined at room temp and at 37 ºC by Brookfield viscometer (DV II pro Model) using spindle no. cP 42 at 20 rpm. The observations are shown in table no.3. Packaging and Pourability: The nasal Mucoadhesive colloidal dispersion was packed in 10 ml capacity HDPE plastic bottles. This packaging system was evaluated for pourability of preparation. Resistance to autoclaving: The teats of packaged system did not become sticky or less resilient and neither the teats nor caps changed in size or shape when autoclaved at 121 ºC and 15 lbs/Sq.inch for 15 minutes, thus the packaged system passed the test of Resistance to autoclaving. Determination of Force of adhesion and Bioadhesive strength 9 The Bioadhesive strength of formulations was evaluated in terms of tensile strength. Freshly excised goat nasal mucosa was used as a model membrane and a lab made assembly was used for the study. This had given the weight in grams required for detachment. Similarly Bioadhesive strength was recorded at different contact times like 6 min and 9 min to evaluate the effect of contact time on Bioadhesive strength of the formulation. In Vitro Release Study:10, 11, 12 In vitro release study of the formulated Mucoadhesive Colloidal Dispersion was carried out in two-chamber diffusion cell through freshly excised goat nasal mucosa. Mucoadhesive Colloidal Dispersion loaded with drug was placed in the donor compartment. 20 ml of 10% methanolic PBS pH 6.4 was placed in the receptor compartment. The temperature of receiver compartment was maintained at the 370C ± 1.00C during experiment and the content of the receiver compartment was stirred using magnetic stirrer. An aliquot of 1 ml was withdrawn from receiver compartment at the intervals of 30 min and replaced with same amount of fresh medium to maintain sink conditions. Aliquot so withdrawn were suitably diluted and analyzed using UV spectrophotometer at 284 nm for drug. In vitro drug release study was carried out for 3 hrs. The observations are shown in table no.3. Histopathological study of optimized formulation 13, 14, 15 Mucosa from one nostril was used as control and the other for treatment with optimized batch. After applying Mucoadhesive Colloidal Dispersion for 3 hours the mucosa was fixed in 10% neutral carbonate buffered formalin solution for 24 hours .It was then cut vertically at the central region in 4mm width. Each section was dehydrated using ethanol solutions and was then fixed in paraffin wax. Various sections were taken. These sections were stained with eosin and hematoxylin and were examined for erosion and degeneration using optiphoto light microscope under 60 x resolution power. Accelerated stability study of optimized formulation 16 The formulation batch F2 was stored at temp and relative humidity as given in ICH guidelines for stability testing ofnasal formulations. The storage condition is as mentioned bellow. 30 ºC ± 2 ºC and 65 % RH for two months. The samples from the preparation were taken and evaluated for pH, viscosity, drug content, and drug release studies at the intervals of 30 and 60 days. The observations are shown in table no.5. RESULTS AND DISCUSSION Statistical parameters for standard curve of Domperidone in 10% Methanolic phosphate buffer pH 6.4- Correlation coefficient (R2 ) = 0.9984Equation for regressed line; Y=0.0248X - 0.0 CONLUSION In the present study it was found that HPMC shows synergistic effect in the viscosity and bioadhesive strength. pH of all the formulations was found to be in between 5.50-6.02 in the nasal pH range (4.5-6.5), Drug content in between 98.87-100.48 %.Marked increase in viscosity was observed with increase in conc. of HPMC K4M in batches F1 to F4.Chitosan initially increases the diffusion of drug but at later stages decreases it which may be due to its polyelectrolyte and complexing behavior. Batch F2 containing methylcellulose 1 % and HPMCK4M 0.2 %was found to be optimum. The developed formulation can be a better alternative to conventional nasal drops and nasal suspensions by virtue of its rheological properties, ability to enhance bioavailability through its longer residence time and ability to sustain the drug release. ACKNOWLEDGEMENTS The authors are very much thankful to Ajanta pharmaceuticals Mumbai for providing me gift sample of drug and Principal Dr. S.S. Khadbadi sir and Prof.U.A. Deokate sir Govt.College of Pharmacy Amravati for providing me Ultrasonic facility. Englishhttp://ijcrr.com/abstract.php?article_id=2195http://ijcrr.com/article_html.php?did=2195REFERENCES 1. Haffejee, N., Du-Plessis, J., Mûller, D.G., Schultz, C., Kotze, A.F., Goosen, C. 2001.Intranasal toxicity of selected absorption enhancers. Pharmazie. 56, 882-887. 2. Ahuja, A., Khar, R.K., Ali, J., 1997. Mucoadhesive drug delivery systems. Drug Devliv. Ind. Pharm. 23, 489-515 3. Stanghellini V, Tosetti C, Paternico A, et al. Risk indicators of delayed gastric emptying of solids in patients with functional dyspepsia. Gastroenterology 1996; 110:1036– 42. 4. Christopher K Rayner, Michel Horowits (2005) new management approaches for gastroparesis-A review, Nature clinical Practice Gastroenterology and Hepatology 2,454-462. 5. Bhise,S.B, Rajkumar M,Controlled Nasal Delivery of Ondansetron HCl,IJPER,41(3) julsep,2007,pp229-235. 6. Balsuramanium J,Kant S,Pandit J K. in-vitro and in-vivo evaluation of the gelrite gum based ocular delivery system for Indomethacin.ActaPharm 2003;53,251-261. 7. Seveinbjorn Gizurarson,C, C Marriott, Gary P. Martin and Erik Bechgaard, The influence of insulin and some excipients used in nasal insulin preparation on mucocilliary clearance.Int.J.of Pharm. Sci. 1990; 65; 243-247. 8. Charoo A, Kohali K, Ali A. Preparation of in situ forming ophthalmic gels of ciprofloxacin hydrochloride for the treatment of bacterial conjunctivitis; in vitro and in vivo studies. J.Pharm.Sci..2003; 92(2), 407-413. 9. Srividya B, Rita M, Cardoza P D, Sustained ophthalmic delivery of ofloxacin from pH triggered in situ gelling systems. j controlled Rel.2001;73,205-211. 10. Gupta A,Garg S ,S Khar R K,Measurement of bioadhesive strength of mucoadhesive buccal tablets: Design of an in-vitro assembly, Indian Drugs,1992;30(4):152-155 11. Rimi Datta,A K Bandyopadhay, Development of new nasal drug delivery system of diazepam with natural mucoadhesive agent from Trigonella foenun-graecum L,Journal of Scientific and Industrial research,vol.64 Dec.2005,pp 973-977. 12. Maitani Y, Uchida M, Takahashi S, Nagaki NM, Nagai T. Effect of bile salts on the nasal mucosa: Membrane potential measurement. Int J Pharm. 1991; 69, 21-27. 13. Yamamoto T, Maitani Y. Morphologic examination of rabbit nasal mucosa after nasal administration of insulin peanut oil suspension and a powder dosage form with soya bean-derived sterylglucoside. Biopharm Bull. 1995; 18 (6), 887-890. 14. Osth K, Paulsson M, Bjork G, Edsman K. Evaluation of drug release from gels on pig nasal mucosa in a horizontal using chamber. J Control Rel. 2002; 83, 377-388. 15. Carstensen J T. Drug stability: Principle and practice. 2nd Edi, Marcel Dekker, New York, 538- 550, 1995. 16. Singh S. Drug stability test guidelines for international registration of pharmaceuticals. Pharma Times. Aug-1997; 29-42.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524132EnglishN-0001November30TechnologyTRIBOLOGY AND DEVELOPMENT OF WEAR THEORY: REVIEW AND DISCUSSION English1326Zamri YusoffEnglish Shamsul Baharin JamaludinEnglishIn this review, the classical and contemporary wear theories and wear mechanisms are discussed. The development of wear theories are started from adhesive and abrasive to delamination theory, mechanical mixed layer (MML) and self lubrication theory are reviewed based on the previous reports. It was found that the adhesive and abrasive are developed based on quantitative approach whereas the delamination, MML and self lubrication theory are developed based on qualitative approach. Each theory has limitation in order to explain the wear theory comprehensively because of different testing system, composite manufacturing technique, type of reinforcement and volume fraction, size as well as hardness. However, a consensus has been reach from a qualitative point view. Theory of wear debris generation mechanism is the consequence of a combination of subsurface, surface and third body dynamic behaviours. This approach applied in order to explain the wear mechanism usually encountered such as adhesive, two-body abrasive, three-body abrasive, oxidation and delamination. Wear mechanism that occurred during dry siding wear of hybrid composite (multiple reinforcement composite consist of combination of hard and soft reinforcement) is combination of various mechanism and highly complex phenomenon. It well known that wear is nature process that what happen at one time is function of all event that occurred previously. Therefore, based on previous work on dry sliding wear of multiple reinforcement composite, it might be proposed that the wear mechanism involved in integrated wear mechanism. Englishabrasive, adhesive, wear theory, delamination, mechanical mixed layer.INTORDUCTION The study of tribology has a long history, extending for several centuries before the word itself was coined in 1965.1 Tribology is the study of friction, lubrication and wear. Professor Duncan Dawson has remarked that whereas the scientific study of friction dates back some 300 years, and that of lubrication more than century, wear has received similar attention for only 50 years.2 So, wear entered the scientific arena rather more recently. Essentially, the design and construction of early machines involved large clearances and rather slow speeds of operation, with the result that, provided gross adhesion or excessive friction could be avoided, changes in dimensions of sliding parts due to wear could often be tolerated with little adverse effect on performance. However, development of high-speed internal combustion engine in the early part of twentieth centuries that provided the initial driving force for the study of wear which has grown in importance to the present day. The understanding of wear mechanisms has developed most rapidly only with the widespread use of electron microscopy and instruments methods of microanalysis over the past 30 years.1 Based on wear studies is so young and so complex, the discrepancies between theories, confusion over nomenclature, and definitions, and inconsistencies between experimental observations is inevitable. However, the foundations of wear studies now seem to be well established. Therefore, this work attempted to review and discuss the development of wear including classical and contemporary wear theories and wear mechanisms based on literature research. Development of Wear Theory Historically, the development of wear knowledge and the ability to quantitatively estimate wear made major progress in period 1950-1965.3 This is the period when the Linear Wear Law (also called the Archard equation) and Khrushov Abrasive Wear law were developed. Wear can be defined as the loss of material that occurs when two surfaces rub against each other.4 Two common forms of wear are adhesive wear5-7 and abrasive wear8-10 . The former occurs when materials of good surface finish and similar hardness are slid against each other and surface forces cause the plucking out and transfer of metallic fragments. The later occurs when abrasive particles or surface protuberances plough and cut fragments from a surface. Adhesive wear theory The first theory of adhesive wear was proposed by Archard.5 This theory was defined wear volume as function of sliding speed, normal load and material hardness. However, this theory ignored the effect of the material’s microstructure on wear and was limited to idealised sliding conditions. This theory was based on a mechanism of adhesion at the asperities and the material removal process was related to a cohesive failure of asperities. The processes of crack nucleation and subsequent growth were disregarded. With the assumption that wear particles could be described as hemispherical particles of the same radius as the contact area, Archard developed the following expression for wear rate, W (volume of material worn): W = KdP 3H (1) Where K = wear coefficient, d = sliding distance, P = applied normal load and H = bulk hardness of material. Archard concluded that the wear rate was proportional to the applied load (assuming that the average size of the contact areas and the particles were constant) and that the wear rate was independent of the apparent area of contact. The theory predicted that enhance wear resistance was associated with increase in hardness. Abrasive wear theory The abrasive wear theory was proposed by Kruschov and Babichev since 1953.8 They defined that abrasive wear occurs when friction between a metal under stress and a harder body or grain. Abrasive wear may take place during friction of a hard rough steel surface against the surface of a softer, for example, bearing metal. Abrasive wear may be due to various mechanisms which cause surface destruction such as cutting, scratching and single or repeated plastic deformation.11 According to Hutching2 mechanisms of abrasive wear can involve both plastic flow and brittle fracture. Under some circumstances plastic flow may occur alone, but both often occur together, even in materials conventionally thought of as ideally brittle. He developed models for abrasive wear separately in two groups of mechanisms; abrasive wear by plastic deformation model and abrasive wear by brittle fracture model. In the first case the hardness of the mating surface is important factor in determining its wear resistance, whereas in the second the fracture toughness is more important, although hardness still plays the role. Chawla and Chawla4 stated during abrasive wear, the surface asperities are worn down and the contact surfaces become mated as shown in Fig. 1. This reduces local contact stress because of the increase in contact area. After this initial abrasive wear, the removal of oxidized particles occurs along the surface. This generally a steady state process in as much as it requires reoxidation of the denuded surface in order to continue removing oxidized particles. The final stage of wear occurs in adhesive mode and occurs if the contact pressure increases to the point of shearing particles. The result of shear is the formation of thin plate-like wear debris sheets. Depending upon applied pressure, the sheets can result in significant material loss. In studies of two-body abrasive wear, commercial coated abrasive papers have been widely used as abrasive mating surfaces.12-15 Various relations have been proposed between the variables of the abrasion process, in which the assumption is commonly made that the number of contacting points, for a given mesh size abrasive paper, is independent of load.9,16,17 Larsen-Badse15 studied the effect of normal load on the number of contact points in the two-body abrasive wear ofmetals and found that the number of scratches made on a copper surface by silicon carbide papers was nearly proportional to the applied load. Similar observations were also found by Sin et al.7 The influence of the nominal grit size of the abrasive particles on the number of contacts was studied by Mulhearn and Samuels14, Sin et al7 and Larsen-Badse15. They found that the number of contacts per unit nominal area was inversely proportional to the square of the mean abrasive particles. Furthermore, Spurr18 studied the surface of aluminium after abrasion by silicon carbide papers. He found that the number of scratches on the abraded specimen surface was proportional to the square root of the applied load rather than directly to the load. Such a relationship was later found also by Miki and Kobayashi.19 Wang and Hutching20 reviewed the Spurr21 reports that the height distribution of the tips of abrasive particles might be normal (Gaussian) but that the abrasive particles which contact the metal surface lie only at the upper end of the normal distribution curve, which may therefore be approximated by a linear distribution over the range of interest. Based on this assumption Spurr21 developed a semi-empirical relationship between the number of contacts and readily measureable quantities, which states that the number of contacts is proportional to the square root of the ratio of the applied load to the mating surface hardness, and inversely proportional to the diameter of the particles. Full experimental results, however, were not reported by Spurr21 , leaving some doubts about the strength of the experimental evidence for this model.     Studies of abrasive wear have been done by several researchers on aluminium composite reinforced by silicon carbide.22-28 Delamination wear theory The most widely quoted adhesive wear theory is that of Archard. Archard’s adhesion theory has been widely accepted, since the phenomenological relationship between the wear volume, sliding speed, normal load and hardness is consistent with experimentally observed results. However, according to Suh6 , the theory is weak because of completely ignores the physics and physical metallurgy of metal deformation and it does not provide any insight to the wear of metals under different sliding conditions. In 1973, Suh proposed a new theory for wear of metal. He proposed that at low sliding speeds, wear debris formation could be described by a delamination theory. The theory is based on the behaviour of dislocations at the surface, sub-surface crack and void formation, and subsequent joining of cracks by shear deformation of the surface.6 Wear processes such as adhesive wear, fretting and fatigue were all related to this same mechanism. The proposed theory predicts qualitatively that the wear particle shape is likely to be thin flake-like sheets and that surface layer can undergo large plastic deformation. Suh6 stated that wear occurred by the following sequential steps: a) Cyclic plastic deformation of surface layers by normal an tangential loads, b) Crack or void nucleation in the deformed layers at inclusions or second-phase particles, c) Crack growth nearly parallel to the surface, d) Formation of thin, long wear debris particles and their removal by extension of cracks to the surface. The rate-determining mechanism of wear showed dependence on the metallurgical structure. When subsurface deformation controlled the wear rate, hardness and fracture toughness were both considered to be major influencing factors. Jahanmir and Suh29 showed that for microstructures containing hard secondphase particles, if sufficient plastic deformation occurred during sliding wear, crack nucleation was favoured at these particles. In this situation, where inter-particle spacing is an important variable, crack propagation controlled the wear rate. Void formation primarily attributed to plastic flow of the matrix around these hard particles. Void formation occurred very readily around the hard particles but crack propagation occurred very slowly. The depth at which the void nucleation was initiated and the void size tended to increase with increased friction coefficient and applied load. Studies of delamination wear mechanism on aluminium composite have been done by several researchers.30-34 For example, Wang et al33 studied the wear behaviour and microstructural changes of 20vol.%SiCw/Al composite under dry sliding using pin-on-ring configuration for a range of load (10 – 80N and sliding speed (1.34 – 5.00 m/s) prepared by squeeze casting method followed by extrusion. They found that at heavy load, volume loss is high, thedominating wear mechanisms are adhesion and delamination wear. In SiC whiskers reinforced aluminium composites, the whiskers plays an important role. At depth of about 30µm below the surface, the shear strain is more than 1.3. The large plastic strain in the deformed layers gives rise to void nucleation and subsurface crack initiation and propagation. The subsurface cracks may initiate and propagate along whisker-matrix interfaces and cause the decohasion of whisker-matrix. Crack propagation by SiC-matrix decohesion process has been observed in SiC particulate reinforced aluminium-silicon alloys.33 The cracks will link to long cracks. With removal of surface material, the cracks become nearer to the surface and the shear strain is increased, this causes the removal of the surface layers by delamination. Delamination wear and the associated nucleation of voids at SiCp/matrix interface during the dry sliding of MMC pin against a steel counterface also reported by Venkatamaran and Sundarajan.34 Mechanical Mixed Layer It should be noted that the adhesive wear theory5 , abrasive wear theory8,12 and delamination theory6 of wear neglect the formation of the tribolayer in their treatment of wear. According to Heilmann et al35, tribolayer phenomena occurs were common in both dry and lubricated sliding wear processes and developed very early before wear debris loosed. The composition of these layers consisted of an intimate (mechanical) mixture of materials derived from both sliding materials and the loose wear debris had the same structure and composition as the transferred layer. On the worn surface of MMCs a mechanically mixed layer (MML) was present. This layer exhibited hardness approximately 6 times that of the bulk composite. There have been a number of research works into the formation of mechanically mixed layers and the nature of wear debris in dry sliding systems, especially during Al alloys sliding against ferrous alloys.36-39 Razavizadeh and Eyre37 reported that the surface layer on the worn surface of Al-Si alloys was formed by fracture and compaction of Al oxide particles during sliding wear. Iwai et al40 noted that a tribolayer was formed on an Al 2024 alloy reinforced with SiCw after a sliding distance of only 50m (40N load and sliding speed 0.1 m s-1 ). Whereas, Zhang and Alpas32 suggested that the surface layers and debris particles contained an aluminium oxide phase with an amorphous structure, in addition to the original phases of α-Fe and α-Al. In contrast, other researchers41 found little or no oxide in the wear debris produced in the sliding wear of Al-alloys in an ambient temperature. Recently, Li and Tandon40 have studied microstructural characterization of mechanically mixed layer and wear debris of Al-Si alloy and Al-Si/SiCp composite against tool steel under dry sliding conditions. They found that wear debris were mostly detached from the MML and had microstructural features similar to those of the MML. The debris and MML were comprised of mechanical mixture of ultrafine equiaxed particles, the constituents of which varied depending on the sliding load at the sliding speed used. At low load, the ultrafine structure consisted of original materials, i.e. α-Al solid solution and α-Fe from steel ring. With an increase in the sliding load, the agglomerated debris of nanocrystaline structure was incorporated with Fe-Al (Si) intermetallic compound and aluminium and iron oxides as a result of mechanical alloying and oxidation caused by the large amount of plastic deformation during the sliding process in association with frictional heating. Deuis et al41 stated the rationale of researchers in order to explain the formation of MML layer. Initially the MMC material experienced bulk deformation and the shear deformation. With increasing deformation the reinforcement particles at the wearing surface fragmented and the number of voids nucleated at the SiCp/matrix interface increased. When the void density reached a critical value, shear stability, as postulated by Rosenfield42 , was initiated at local subsurface regions. This resulted in the occurrence of turbulence plastic flow, during which time iron and iron oxide debris was mixed in the surface MMC material, resulting in the formation of the MML layer. Venkatamaran and Sundarajan34 stated that the presence MML layer most probably controlled the wear rate. The formation of wear debris was directly related to delamination wear active within this region. Self Lubrication Theory Apart from hard second-phases particle in soft matrix composite, a soft secondphase particles in hard and strong matrix composites are widely used in sliding bearing applications. They possess low coefficient of friction and adapt to diverse operational conditions. Tribological properties of such materials depend in the matrix and the second-phase, as well as the size, shape and concentration of the second-phase particles. The main problem is optimization of the microstructure for the best tribological performance. This task is complicated and requires theoretical analysis. Alexeyev and Jahanmir45 have attempted to develop self lubrication theory based on quantitative analysis. Slip-line field analysis of plastic deformation is used to analyze the processes of deformation and flow of the soft phase toward the sliding surface. They found a general relationship for deformation and flow of soft phase is obtained. It shows that the properties as well as size and shape of hard matrix and soft second-phase particles control the processes of deformation and flow of the soft phase as shown in Fig. 2. Solid lubrication is introduced from the solid lubricant cavities (reservoirs) dispersed within the material. These cavities are typically filled with graphite, MoS2 or soft metal such as Pb, Sn or Ag. The solid lubricant particles deform by the sliding action of the mating surface and are squeezed out toward the surface, forming a soft interfacial film. The presence of this film is believed to be responsible forthe observed low friction and reduced wear. When the solid lubricant film is worn away, the resulting increase in friction accentuates plastic deformation of the surface layer and forces more material from second-phase particles toward the surface, thus re-forming the worn film. The beneficial effect of selflubrication depends on the thickness of the film, the relative plastic properties of the film and the sublayer, and the pressure experienced by the soft film and sublayer43. Very few studies have been done on the processes of film formation and destruction.44,45 The exact mechanism for the adhesion of the film and substrate remain unclear. In order to understand the tribological behaviour of metal matrix selflubricating composite, the basic mechanism of the formation of lubricating films must be developed. The early studies of wear behaviour on self-lubricating aluminium composite using graphite as solid lubricant have been done by several researchers.46-50 However, study on the formation of lubricating film at worn and mating surface are did not discussed thoroughly until Liu et al.44 He attempted to describe the smearing process of the embedded graphite particles in aluminium 2014 alloy during sliding in great detail based on qualitative analysis by optical microscope. They found that the reduction in friction and wear of the aluminium-graphite composites is result of the embedded graphite particles during sliding, forming a lubricating film on both the tribosurface of the composite and the steel mating surface. Whereas, Alexeyev and Jahanmir47 attempted to describe the process of film formation in self-lubricating composites and deformation of the film based on quantitative analysis by the slip-line field method. The results show that the size of second-phase particles in the composite, the relative shear yield limit of the matrix and the soft phase, and the thickness of the film control the tribological performance of these composites. Lin et al49 also studied the process and tribological behaviour of Al6061/graphite particulate composite. They found that the tribological behaviour of the composite depends on the hardness of the matrix, the rate of release graphite particulates, the structure of the solid lubricating film deposited on the wearing material, and the structure of Al chip clusters General discussion Development of five wear theory might be summarized as shown in Fig. 3. However, in 1995, Sanino and Rack51 proposed the theory based on debris generation in order to shows the wear mechanism in integrated manner. They stated that wear debris generation mechanism is the consequence of a combination of subsurface, surface and third body dynamic behaviours. This approach applied in order to explain the wear mechanism usually encountered such as adhesive, two-body abrasive, three-body abrasive, oxidation and delamination. Based on literatures, since year 2000, there are some research focuses on the role of soft reinforcement particle in hybrid composite.52-61 Aluminium hybrid matrix composite consist of two or more reinforcement added in aluminium matrix. The soft reinforcement likes graphite and carbon fibre, whereas the hard material likes Saffil fibre or SiC particles in hybrid composite. Some researchers have studied the sliding wear behaviour of aluminium hybrid composite found that the hybrid composite showed the best performance in wear resistance. Their result showed more stable tribo-layers on the contact surfaces of the graphitic composites compared to non-graphitic composites However, the hard constituents in the tribo-layers were the scuffing damage that they inflicted on the counterface. Wear mechanism that occurred during dry siding wear of hybrid composite (multiple reinforcement composite consist of combination of hard and soft reinforcement) is combination of various mechanism and highly complex phenomenon. It well known that wear is nature process that what happen at one time is function of all event that occurred previously. Therefore, based on previous work on dry sliding wear of multiple reinforcement composite, it might be proposed that the wear mechanism involved in integrated wear mechanism as shown in Fig. 4. CONCLUSION The purpose of this paper was to highlight the development of wear theory since 1950’s up to contemporary theory. It can be concluded as follow: Adhesive wear is influenced by critical parameters such as applied load, speed and environment. Abrasive theory is influenced by contact geometry, matrix and hard reinforcement phase as well as interface characteristics. Delamination theory is influenced by changing of subsurface behavior because of load, speed, fracture toughness as well as creep/fatigue effect. MML theory’s influenced by mechanical and chemical reaction during sliding process. Self lubrication theory is influenced by the smearing of soft reinforcement phase on the contact surfaces during sliding process. Wear mechanism that occurred during dry siding wear of hybrid composite (multiple reinforcement composite consist of combination of hard and soft reinforcement) is combination of various mechanism and highly complex phenomenon. Englishhttp://ijcrr.com/abstract.php?article_id=2196http://ijcrr.com/article_html.php?did=2196REFERENCES 1. Stachowiak GW. Wear: Materials, Mechanisms and Practice. John Wiley and Sons, Ltd. 2005: 2-3. 2. Hutchings IM. Tribology: Friction and Wear of Engineering Materials. Butterworth-Heinemann 1992:5-6. 3. Finkin EF. Speculations on the theory of adhesive wear. Wear 1972; 21:103-114. 4. Chawla N, Chawla KK. Metal Matrix Composites. Springer Science Business Media, Inc. 2006:337-8. 5. Archard HC. Contact and rubbing of flat surface. J. Appl. Phys. 1953; 24: 981-988. 6. Suh NP. The delamination theory of wear. Wear 1973; 25: 111-124. 7. Sin H, Saka N, Suh NP. Abrasive wear mechanisms and the grit size effect. Wear 1979; 55: 163-190. 8. 8.Khruschov MM, Babichev MA. Resistance to abrasive wear and the hardness of metals (in Russian), Dokl. Akad. Nauk SSSR 1953; 445- 448. 9. Rabinowicz E, Mutis A. Effect of abrasive particle size on wear. Wear 1965; 8: 381-390. 10. Zhang Z, Zhang L, Mai YM. Modeling steady wear of steel/Al2O3-Al particle reinforced composites system. Wear 1997; 211: 147-150. 11. Khruschov MM. Principle of abrasive wear. Wear 1974; 28: 69- 88. 12. Avient BWE, Gorddard J, Wilman H. An experimental study of friction and wear durin abrasion of metals, Proc. Roy. Soc. (London) 1960; Ser. A258, 159-180. 13. Avient BWE, Wilman H. New features of the abrasion process shown by soft metals; the nature of mechanical polishing, J. Applied Phys. 1962; 13: 521-526. 14. Mulhern TO, Samuels LE. The abrasion of metals: a model of the process. Wear 1962; 5: 478-498. 15. Larsen-Basse J. Influence of grit diameter and specimen size on wearduring sliding sliding abrasion. Wear 1968; 12: 35-53. 16. Moore MA, King FS. Abrasives wear of brittle solids. Wear 1980; 60: 123-140. 17. Zum Gahr KH. Microstructure and wear of materials, Elsevier, Amsterdam 1987, p.p.80-124, 351- 477. 18. Spurr RT. Temperatures reached during sliding. Wear 1976; 55: 259. 19. Miki H, Kobayashi S. An equation for the centre-line average roughness of material slide against abrasive paper. Wear 1980; 65: 47- 53. 20. Wang AG, Hutchings IM. The number of particle contacts in twobody abrasive wear of metals by coated abrasive papers. Wear 1989; 129: 23-35. 21. Spurr RT. The nature of contact during abrasion. Wear 1981; 67: 375-379. 22. Lin SJ, Liu KS. Effect of aging on abrasion rate in an Al---Zn---Mg--- SiC composite. Wear 1988; 121: 1- 14 23. Wang A, Rack HJ. Abrasive wear of silicon carbide particulate—and whisker-reinforced 7091 aluminum matrix composites. Wear 1991; 146: 337-348. 24. Lee HL, Lu WH, Chan SLI. Abrasive wear of powder metallurgy Al alloy 6061-SiC particle composites. Wear 1992; 159: 223-231. 25. Song WQ, Krauklis P, Mouritz AP, Bandyopadhyay S. The effect of thermal ageing on the abrasive wear behavior of age-hardening 2014 Al/SiC and 6061 Al/SiC composites. Wear 1995; 185: 125- 130. 26. Ahlatci H, Candan E, Iu HC. Abrasive wear behavior and mechanical properties of Al-Si/SiC composites. Wear 2004; 257: 625- 632. 27. Das S, Mondal DP, Sawla S, Ramakrishnan N. Synergic effect of reinforcement and heat treatment on the two body abrasive wear of an Al-Si alloy under varying loads and abrasive sizes. Wear 2008; 264: 47- 59. 28. Modi OP. Two-body abrasion of a cast Al-Cu (2014 Al) alloy-Al2O3 particle composite: influence of heat treatment and abrasion test parameters. Wear 2001; 248: 100- 111 29. Jahanmir S, Suh NP. Mechanics of subsurface void nucleation in delamination wear. Wear 1977a; 44: 17-38. 30. Argon AS. Formation of cavities from nondeformable second-phase particles in low temperature ductile fracture. Trans. ASME, Ser. H. J. Engng. Mater. Technol. 1976; 98: 60-68. 31. Saka N, Pamies-Teixeira JJ, Suh NP. Wear of two-phase metals. Wear 1977; 44: 77-86. 32. Alpas AT, Zhang J. Effect of SiC particulate reinforcement on the dry sliding wear of aluminium-silicon alloys (A356). Wear 1992; 155: 83- 104. 33. Wang DZ, Peng HX, Liu J, Yao CK. Wear behavior and microstructural changes of SiCw-Al-Al composite under unlubricated sliding friction. Wear 1995; 184: 187-192. 34. Venkataraman B, Sundarajan G .The sliding wear behaviour of AlSiC particulate composites-II, The characterization of subsurface deformation and correlation with wear behaviour. Acta Mater. 1996ab; 44: 451-460. 35. Heilmann P, Don J, Sun TC, Rigney DA, Glaeser WA. Sliding wear and transfer. Wear 1983; 91: 171-190. 36. Shivanath R,Sengupta PK, Eyre TS. Oxidative wear aluminium-silicon alloys. Br. Foundryman 1977; 70: 349-356. 37. Razavizadeh K, Eyre TS. Oxidative wear of aluminium alloy. Wear 1982; 79: 325-333. 38. Subramaniam C. On mechanical mixing during dry sliding of aluminium -12.3 wt. % silicon alloy against copper. Wear 1993; 161: 63-60. 39. Iwai Y, Yoneda H, Honda T. Sliding wear behavior of SiC whisker-reinforced aluminum composite. Wear 1995; 181: 594- 602. 40. Li XY, Tandon KN. Microstructural characterization of mechanically mixed layer and wear debris in sliding wear of an Al alloy and an Al based composite. Wear 2000; 245: 148-161. 41. Deuis RL, Subramaniam C, Yellup JM. Dry sliding wear of aluminium composite-a review. Composite Science and Technology 1997; 57: 415-435. 42. Rosenfield AR. A shear instability model of sliding wear. Wear 1987; 116: 319-328. 43. Bowden FP, Tabor D. The Friction and Lubrication of Solids, Vols I and II. Oxford University Press, Oxford 1964. 44. Liu YB, Lim SC, Ray S, Rohatgi PK. Friction and wear of aluminum-graphite composites: the smearing process of graphite during sliding. Wear 1992; 159: 201-205. 45. Alexeyex N, Jahanmir S. Mechanics of friction in selflubricating composite materials II: Deformation of the interfacial film. Wear 1993b; 166: 49-54. 46. Gibson PR, Clegg AJ, Das AA. Wear of cast Al-Si alloys containing graphite. Wear 1984; 95: 193-198. 47. Das S, Prasad SV, Ramachandran TR. Microstructure and wear of cast (Al-Si alloy) graphite composites. Wear 1989; 133:173-187. 48. Jha AK, Prasad SV, Upadhyaya GS. Sintered 6061 aluminum alloy-solid lubricant particle composites: sliding wear and mechanisms of lubrication. Wear 1989; 133: 163- 172. 49. Lin CB, Chang RJ, Weng WP. A study on process tribological behaviour of Al alloy/Gr. (p) composite. Wear 1998; 217: 167- 174. 50. Goto H, Uchijo K. Wear mechanism of Al-Si alloy impregnated graphite composite under dry sliding. Wear 2005; 259: 613-619. 51. Sannino AP, Rack HJ. (1995). Dry sliding wear of discontinuously reinforced aluminium composites: review and discussion. Wear 1995; 189(1-2): 1-19. 52. Riahi AR, Alpas AT. The role of tribo-layers on the sliding wear behavior of graphitic aluminium matrix composites. Wear 2001; 251: 1396-1407. 53. Fu HH, Han KS, Song JI. Wear properties of Saffil/Al, safil/Al2O3/Al and Saffil/SiC/Al hybrid metal matrix composites. Wear 2004; 256: 705-713. 54. Jun D L, Hui Y, Rong YS, Fang LW. Dry sliding friction and wear properties of Al2O3 and carbon short fibres reinforced Al-12Si alloy hybrid composites. Wear 2004; 257(9-10): 930-940 55. Hui LY, Jun D, Rong YS, Wei W. High temperature friction and wear behaviour of Al2O3 and/or carbon short fibre reinforced Al-12Si alloy composites. Wear 2004; 256(3-4): 275-285. 56. Basavarajappa S, Chandramohan G, Mahadevan A, Thangavelu M, Subramanian R, Gopalakrishnan P. Influence of sliding speed on the dry sliding wear behaviour and the subsurface deformation on hybrid metal matrix composite. Wear 2007; 262(7-8): 1007-1012. 57. Benal MM, Shivanand HK. Effects of reinforcement content and ageing duration on wear characteristics of Al (6061) based hybrid composites. Wear 2007; 262: 759-763. 58. Naplocha K, Granat K. Dry sliding wear of Al/Saffil/C hybrid metal matrix composites. Wear 2008; 265(11-12): 1734-1740. 59. Suresha S, Sridhara BK. Effect of addition of graghite particulates on the wear behaviour in aluminiumsilicon carbide-graphite composites. Materials and Design 2010; 31(4): 1804. 60. Suresha S, Sridhara BK. Effect of silicon carbide particulates on wear resistance of graphitic aluminium matrix composites. Materials and Design 2010; 31(9): 4470-4477. 61. Wang YQ, Afsar AM, Jang JH, Han KS, Song JI. Room temperature dry and lubricant wear behaviours of Al2O3f/SiCp/Al hybrid metal matrix composites. Wear 2010; 268(7-8): 863-870.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524132EnglishN-0001November30HealthcareSINGLE BOUT OF AEROBIC AND RESISTANCE EXERCISE ON REACTION TIME AND WORKING MEMORY IN NORMAL SUBJECTS - A RANDOMIZED CONTROL TRIAL English2736M.PremkumarEnglish B.SankarmaniEnglish K. ManivannanEnglish Hussaini zartaj fatemaEnglishObjectives: To find out the effect of single bout of aerobic and resistance exercise on reaction time and working memory in normal subjects. Design: 30 under graduate both gender students were selected randomly using a stratified sampling method and divided into 3 groups of 10 subjects respectively. Subjects were given the working memory task extracted from the modified Sternberg test and the reaction time task. Subjects were tested prior to the exercise and took pre test values. Group 2 was given resistance exercise with multi gym and Group 3 was given aerobic exercise with tread mill walking with proper rest intervals while the Group 1 was kept as control. After the exercise was performed, they were tested again for working memory with differently prepared sheets and reaction time. The exercise given to the subjects were prolonged for 30 minutes. All subjects were given a ten minutes warm up and a cool down exercises. Result: Statistical analysis using paired t test showed mean and standard deviation for reaction time for Group 1: 0.2290± 3.281, 0.2230±2.983, and 0.2140± 3.688 as pre, post and after 30 minutes respectively with p value ? 0.668, 0.350 between pre and post, and pre and after 30 minutes respectively. For Group 2: 0.2270± 3.592, 0.2030±4.547, 0.2090± 4.383 as pre, post and after 30 minutes respectively with p value ? 0.158, 0.331 between pre and post, and pre and after 30 minutes respectively. For Group 3: 0.2150± 3.206, 0.2250±2.915, 0.2140± 3.921 as pre, post and after 30 minutes respectively with p value ? 0.472, 0.924 between pre and post, and pre and after 30 minutes respectively. Conclusion: There was no statistically significant difference in the effect of single bout aerobic and resistance exercise on reaction time and working memory after single bout of aerobic and resistance exercise in normal subjects. Englishsingle bout, aerobic exercise, resistance exercise, reaction time, working memoryINTRODUCTION If you exercise the body, you also exercise the mind. 1 The effect of physical activity on brain and cognition has grown in interest in recent times with an increasing number of reports indicating that chronic participation and single, acute bout of exercise benefit a host of cognitive processes. 2 In the absence of a rich literature base examining acute resistance exercise and cognition, some understanding of this relationship may be gained through the examination of research on chronic resistance training. Accordingly, the investigation of acute resistance exercise may provide further insight into the overall relation of health behaviours such as physical activity to cognition. 3 Much of the new research suggests that aerobic exercise can actually promote the growth of new brain cells. This contradicts earlier beliefs that the brain stopped producing new cells relatively early in its development. In one study recent study researchers found that adult mice doubled their number of brain cells in the hippocampus when they had access to running wheels 7 . The hippocampus is a structure in the brain that is vital for memory and learning. A similar study showed that exercising mice had two and half times the growth of new neurons in the dentate gyrus, another area of the brain important in memory. 4-8 Working memory is the ability to keep information on line for a brief period of time, which is essential for many cognitive tasks such as control of attention and problem solving. Improving working memory capacity leads to better performance on several tasks that require working memory and control of attention and it translates to increased attentiveness in everyday life .6 Aerobic exercises clearly improves the speed of recall, and much if the research points to an effect on the quality of mental functioning and the amount of recall. It releases endorphins, the neurotransmitters that relax us into a state of cortical alertness. It decreases the likelihood of depressive symptoms two to one over individuals with little or no physical activity. It also increases the number of capillaries around the neurons of the brain, increasing the supply of blood and oxygen to reach the brain. Finally it results in faster, improved reaction time. 6 Physical activity improves not only physical fitness but also cognitive functions. 9 Researchers has proposed three reasons why exercise improved fitness and also enhanced cognitive functioning. They proposed that increased transportation of oxygen and glucose to the brain, as well as increased self esteem and decreased physiological distress, would result in improved performance on complex psychological tasks.10 Executive attention is thought to be at the heart of working memory.11 Resistance exercise and aerobic exercise represent a distinct spectrum of exercise that is characterized by different physiological demands (i.e., cardiovascular, musculoskeletal, metabolic, etc.). To date, the vast majority of research has investigated changes in cognition after an acute bout of aerobic exercise, whereas only a single study has investigated the effect of acute resistance exercise on cognitive function.12 Lack of studies comparing the effect between acute aerobic and resistance exercise on working memory. The purpose of this current study is to expand the acute exercise – cognition database, to include resistance exercise and compare it with aerobic exercise during performance on a working memory task. To evaluate the effect of single bout of aerobic and resistance exercise on working memory and reaction time. : MATERIALS AND METHOD Study design A Randomized Control Trial. Group 1: Subjects not performing both aerobic and resistance exercises. Group 2: Subjects performing whole body resistance exercise for 30 minutes. Group 3: Subjects performing aerobic exercise on treadmill for 30 minutes. Subjects: Number of subjects:-30 (3 groups each having 10 subjects), Students of the Sumandeep Vidyapeeth University. Inclusion criteria: Age: 19-25 years Sex: Both Male and Female Students who have raw knowledge about aerobic and resistance exercise.Exclusion criteria: Musculoskeletal condition Neurological condition Psychiatric illness Cardio respiratory conditions Aerobic performers and regular exercisers. Procedure: 30 numbers of subjects were recruited from Sumandeep Vidyapeeth who were fulfilling the inclusion criteria of age 19 – 25 years, both male and female and whom have raw idea about aerobic and resistance exercise. Students with musculoskeletal condition, neurological condition, psychiatric illness, cardio respiratory conditions, and regular aerobic performers and sports persons were excluded. 30 subjects divided into 3 groups, 10 each through stratified random sampling method. Experimental group 1 was given resistance exercise with multi gym. Experimental group 2 was given aerobic exercise with treadmill whereas the other was kept as control group. The exercise duration was kept for 30 minutes with 2 rest intervals of each 3 minutes and additional 10 minutes of warm - up and cool – down. Single session was carried out. Subjects were given the Modified Stanford Working Memory Task and the reaction time was tested prior to the session. After the exercise was performed they were tested again for working memory with differently prepared sheets and reaction time. The tasks were repeated 30 minutes after the session. Then data were documented for results. Data analysis: Data was analysed by using paired and independent‘t’ test with the help ofStatistical Package for Social Sciences (SPSS) version 11.0 for windows and p? 0.05 was kept as highly significant. The results show no significance between the results of both reaction time and working memory between Pre-exercise, Immediate Post-exercise and 30 minutes Post-exercise in all the three groups i.e. control, aerobic and resisted groups. i.e., there is no effect of single bout of aerobic and resisted exercise on reaction time and working memory. DISCUSSION For centuries, people have been intrigued with the brain and in finding a way to tap into its vast potential. It seems, though, that each new discovery brings more questions than answers. Literature review shows a great deal of evidence regarding the reaction times following all exercise conditions and were seen to be shorter when compared to the baseline condition. Ozyemisci-Taskiran. O, Gunendi Z et al in their study concluded that a single bout of cycling exercise significantly improves pre-motor fraction of reaction time in healthy young sedentary subjects.13 Considering that resistance exercise exerts a very different metabolic response compared with aerobic exercise, manifested by lower oxygen consumption despite higher levels of muscular exertion, and lower levels of systemic blood flow, it may be possible that resistance exercise affects cerebral blood flow differently compared with aerobic exercise. Pontifex MB, Hillman CH et al (2009) studied influence of acute bouts of aerobic versus resistance exercise on the executive control of working memory and they concluded that acute exercise-induced changes in cognition are disproportionately related to executive control and may be specific to the aerobic exercise domain but according to my study we did not get a significant difference in the results of working memory between resisted and aerobic groups. Although within the groups we get certain degree of improvement but when the groups are compared as a whole the results are not significant.3 The reason for such results could be because the study was concise and the sample size was only 30.The results may even vary with difference in the intellectual level of various subjects. The concentration level of the subjects as well as the environment in which they performed the exercises and the tasks could also be considered as a major factor affecting the results. Their results might have varied even due to differences in the physical activities in their day to day lives. The time at which they performed the tasks would also affect the results as the subjects are fresher in the mornings. The working memory task and reaction time task could have been made more precise. The weight given to the subjects in the resisted group was kept constant for all but the weight could have been varied by measuring their repetition maximum. It is very pleasing and giving immense pleasure to say this study gives very much advancing ideas about the relationship between the exercise domains with cognitive function. This study can be explored in so many aspects including the various forms of exercise related with higher mental function. It is giving extended inputs to study the expanding horizons of various forms of exercise on cognitive functioning. CONCLUSION There was no statistically significant difference in the effect of single bout aerobic and resistance exercise on reaction time and working memory after single bout of aerobic and resistance exercise in normal subjects. ACKNOWLEDGEMENTS All the subjects had included in this study cooperated immaculately to fulfil the endeavour to a great success. Our patients greatly motivated us to excel in this research. We collogue helped immensely to carry forward this study without any hiccups. We acknowledge our deepest thanks to the above persons who contributed greatly to this study. We extend our thanks to Dhiraj general hospital and the research wing of Sumandeep Vidyapeeth and its management.   Englishhttp://ijcrr.com/abstract.php?article_id=2197http://ijcrr.com/article_html.php?did=2197REFERENCES 1. Tom Stormcrowe (Pseudonym) Creative Commons, aerobic exercise, http://theamazingshrinkingman.spaces.li ve.com/blog/cns!82AE0160B9B87B82! 2310.entry, ©2006- Accessed on 13/02/2009. 2. Hillman CH, Erickson KI, Kramer AF (2008) Be smart, exercise your heart: exercise effects on brain and cognition. Nat Rev Neurosci 9:58–65. 3. PONTIFEX, M. B., C. H. HILLMAN, B. FERNHALL, K. M. THOMPSON, and T. A. VALENTINI. The Effect of Acute Aerobic and Resistance Exercise on Working Memory. Med. Sci. Sports Exerc., Vol. 41, No. 4, pp. 927–934, 2009. 4. Ariniello, Leah, Brain Briefings. Society for Neuroscience. Washington, D.C.: www.tarleton.edu/~sanderson/AEROBI C EXERCISE AND THE BRAIN.doc , Sept 2002. Accessed on 14/02/2009. 5. Brink, Susan (1995). Expanded Academic ASAP. U.S. News and World Report. May 15, V118N19 p.76. www.tarleton.edu/~sanderson/AEROBI C EXERCISE AND THE BRAIN.doc, Accessed on 14/02/2009. 6. Howard, Pierce (2001). The Owner’s Manual For The Brain. Atlanta – Austin: Bard Press. www.tarleton.edu/~sanderson/AEROBI C EXERCISE AND THE BRAIN.doc Howard, Pierce J., Ph.D. The Owner’s Manual for the Brain: Everyday Applications from Mind-Brain Research, 2nd Ed. Austin, TX: Bard Press, 1999, 829 pp. Accessed on 16/02/2009. 7. Matheson, Gordon (2000). Is Exercise Brain Food? [online] The Physician And Sports Medicine, Vol. 28, No. 11, November. Available: http://www.physsportsmed.com, www.tarleton.edu/~sanderson/AEROBI C EXERCISE AND THE BRAIN.doc. Accessed on 16/02/2009. 8. Priest, Laurie (1993). The Case for Physical Education. [online]. Orange County Department of Education. Available: http://www.ocde.kiz.ca.us. Accessed on 20/02/2009. 9. Samuele M. Marcora,Walter Staiano, and Victoria Manning Mental fatigue impairs physical performance in humans Journal of Applied Physiology March 2009 vol. 106 no. 3 857-864. 10. ELSAYED, M.; ISMAIL, A. H. y YOUNG, R. J. (1980): Intellectual differences of adult men related to aged and physical fitness before and after an exercise program. Journal of Gerontology, 35, 383-387. 11. Benjamin A. Sibley and Sian L. Beilock Journal of Sport and Exercise Psychology, 2007, 29, 783-791 12. Krus DM, Wapner S, Werner H. Studies in vicariousness: effect of muscular involvement on visual threshold. Am J Psychol.1958; 66:603–8. 13. Ozyemisci-Taskiran O, Gunendi Z, Bolukbasi N. The effect of a single session submaximal aerobic exercise on premotor fraction of reaction time: an electromyographic study. Clin Biomech (Bristol, Avon). 2008 Feb; 23(2):231-5. Epub 2007 Oct 24.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524132EnglishN-0001November30HealthcareSTUDY OF DEGENERATIVE CHANGES IN UTERINE LEIOMYOMAS English3741Ramesh B.HEnglish Shashikala PEnglish Kavita G.UEnglish DoddikoppadEnglish Chandrasekhar H.REnglishLeiomyomas are the commonest tumors in female genital tract and in the body as a whole. These benign tumors of smooth muscles occur in 20-30% females in the reproductive age group and tend to be symptomatic. A study of 314 uterine leiomyomas revealed some form of degeneration in 45.79 % of specimens. Hyaline degeneration occurred most frequently, accounting for 94.11% of all types of degeneration. Cystic change was observed in 3.5 % of cases. Calcification occurred in 5.15 % of cases, Red degeneration in 0.74% of cases whereas sarcomatous change was not encountered at all. EnglishINTRODUCTION Uterine leiomyomas, commonly referred to as fibroids are the most common benign tumor of the female genital tract. However, their true prevalence is probably underestimated, as the incidence at histology is more than double the clinical incidence.1 Regardless of their generally benign euplastic character, uterine fibroids are responsible for significant morbidity in a large segment of the female population. Although the cause or causes of fibroids are unknown, the scientific literature now contains a sizeable body of information pertaining to the epidemiology, genetics, hormonal aspects, and molecular biology of these tumors. 2 We have made an attempt to study the various degenerative changes that occur in leiomyomas. AIM AND OBJECTIVES To know the prevalence and various types of degenerative changes encountered in leiomyomas. MATERIAL AND METHODS This is a prospective study of degenerative changes encountered in leiomyomas over a period of two years at a tertiary hospital in Davangere, which is located in the central part of Karnataka. A total of 1830 specimens comprising of hysterectomies (1827) and myomectomies (3) were submitted to gross and microscopic examination. Of these, 314 specimens had leiomyomas which were included for the study. Specimens were fixed in 10% formalin and studied in detail to know the size, site, consistency, appearance and secondary changes. Apart from taking routine sections, particular attention was paid to the sampling of areas showing softening and or discoloration. Tissues were processed routinely and 4-5 µ thick sections were taken from paraffin blocks. Routine sections stained with hematoxylin and eosin were thoroughly studied microscopically to identify the various secondary changes like hyaline degeneration, cystic degeneration, calcification, red degeneration, myxomatous, mucoid, necrotic change, fatty degenerations and sarcomatous changes. RESULTS Of the 314 specimens of leiomyoma studied, associated degenerative changes were seen in 136 leiomyomas (45.79%). Hyaline change, the commonest form of degeneration, was seen in 128 (94.11%) of the 136 leiomyomas, whereas the remaining (5.88%) were associated with other degenerative changes. On histologic examination, typical hyaline change is characterized by diffuse homogenous glassy pink structure with marked acellularity. Grossly the mean size of these leiomyomas was 4.8cms. Cystic change (characterized by formation of cystic spaces of varying sizes but without an epithelial lining), which is an invariable accompaniment of hyaline change was observed in 11 cases (8.09%). Eight (5.88%) of these, were also associated with hyaline change. In five (4.11%) leiomyomas, a large part of the tumor was cystic containing colorless or straw colored fluid. Six (4.41%) leiomyomas showed mucoid degeneration, which also resulted in cystic change. Out of 7(5.15%) leiomyomas with calcareous degeneration, 4 were detected grossly and 3 showed microscopic foci of purplish amorphous lake produced by haematoxylin. These gave a gritty feeling while sectioning the tumor. Completely calcified leiomyoma was observed in one (0.74%) case, so called womb stone. Fatty change was observed in two cases (1.47%) Leiomyoma with hemorrhage was observed in 2 cases (1.47%), which included a case of red degeneration that occurred in absence of pregnancy. Myxoid change and Necrosis were also found in 2 cases (1.47%) each. Macroscopically leiomyoma with infection was not evident, but was detected microscopically in one case (0.74%). Leiomyoma with infarction was discernible in one (0.74%) case. However, there was no case of sarcomatous degeneration in the present study. Variants of leiomyoma constituted 0.96% of total 314 cases, which included one case each of cellular, epitheloid and symplastic leiomyomas. DISCUSSION Degenerative changes in leiomyomas are considered to be due to inadequate blood supply, and the type of degenerative change seems to depend on the degree and rapidity of onset of the vascular insufficiency 3, 4 . Degenerative changes in various studies varies from 65% to 100% 3,5 . Hyaline change: It is generally accepted that hyaline change is the commonest form of degeneration seen in leiomyomas3, 5, 6. In the present study also it was the commonest form of degeneration encountered. he incidence of leiomyomas with calcification was 2.22% which is consistent with other studies by Reddy and Malathy (1963, 2.5%), Torpin et al (1942, 2.4%) 3, 5. We report a completely calcified leiomyoma (so called Womb stone) in one case. Fatty degeneration in leiomyomas is very uncommon and its pathogenesis is somewhat controversial3, 4, 8. Starry (1925) believes that it is due to lipomatosis of the stroma of the uterine tumor, whereas Willis (1958) states that the adipose tissue is formed by metaplasia7 .Fatty change was observed in 0.64% of cases, similar to studies by Persaud and Arjoon (1970) and Reddy and Malathy (1963,) who reported low incidence of fatty change3,5. It should be differentiated from uterine lipoma, a rare tumor of obscure histogenesis3 . Jeffcoate (1967) considered myxomatous degeneration in leiomyomas to be rare, while Persaud and Arjoon (1970) reported higher incidence of 12%3 . Myxoid change was observed in 2 cases (0.64%) in our study. Myomas with mucoid degeneration (1.91%) also result in cystic change in the study. Persaud and Arjoon3 (1970) reported higher incidence of 5.36%. Leiomyoma with hemorrhage was reported in 2 cases in contrast to Norris and Zaloudek (1981)6 observation of 11% . One case of red degeneration (0.74%) showed hemorrhage with hyaline change microscopically, and was not associated with pregnancy in our study. Rosario pinto 1968, (1.2%), Persaud and Arjoon1970 (3.3%), and Reddy and Malathy 1963 (2.5%), found low incidence of red degeneration in patients without pregnancy 3, 5, 6. Faulkner 1947 estimated the frequency of red degeneration in leiomyomas to be 7-8%. Boyd reported that among 38 examples of red degeneration operated upon, 29% were associated with pregnancy 3 . Sarcomatous change in leiomyomas is rare. Corscaden and Singh indicated in their study that the true incidence of sarcoma developing within uterine leiomyomas is not more than 0.13%, and probably as low as 0.04%. Various other studies have also reported low incidence of sarcomatous change 3, 8. However, there was no case of sarcomatous degeneration in our study. CONCLUSION Leiomyomas are the most common benign tumors of the uterus. Hyaline change is the commonest degenerative change encountered and also coexists with other degenerative changes. Since leiomyomas are known to occur even in young reproductive age group, proper understanding, knowledge, intervention as well as medical advice regarding the tumor can help in preventing depression and anxiety related to the disease in many patients. Englishhttp://ijcrr.com/abstract.php?article_id=2198http://ijcrr.com/article_html.php?did=2198REFERENCES 1. Okolo S .Incidence, etiology and epidemiology of uterine fibroids, best practice and research. Clinical obstetrics and gynecology . 2008 ;22 (4): 571–88. 2. Gordon P, Andersen FJ and Dixon D. Etiology and Pathogenesis of Uterine Leiomyomas,A Review Journal article byEnvironmental Health Perspectives. 2003; Vol. 111. 3. Persaud V and Arjoon P.D. Uterine Leiomyoma, Incidence of Degenerative change and a correlation of associated symptoms. Obst. and Gynec.1970; 35 (3):432-36. 4. Haines M and Taylor C.W. Adenomyosis and Fibromyoma, In Gynecological Pathology, 2nd edition. Ebinburg London, Churchill Livingstone. 1975;158-218 5. Pinto R,.Uterine fibromyomas. J. of Obstet. and Gynaecol. Of India, 1968;(18) 101-07. 6. Zaloudek ,C and Norris HJ . Mesenchymal Tumours of uterus In Blaunstein’s Pathology of Female Genital Tract. Editor R.J.Kurmann. IInd edition. New York, Springer-verlag, 1987;374-02 7. Padubidri VG and Daftary S.N. New Growths of uterus In Shaw’s text book of Gynaecology, Howkins and Browne.10th Edition. New Delhi, Churchill Livingstone.1989; 399-427. 8. Masani M.M.: New growths of cervix and uterus In A text book of Gynaecology. 6th Edition. Bombay, Popular Prakashan. 1971;313-417.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524132EnglishN-0001November30HealthcareSYNTHESIS AND BIOLOGICAL EVALUATION OF 3,5- DIARYL-1-PHENYL-2-PYRAZOLINES AS ANTIBACTERIAL, ANTI-INFLAMMATORY AND ANALGESIC AGENTS English4254Anjan KumarEnglish Sradhasini RoutEnglish Chandrasekar PandaEnglish M.B.V.RajuEnglishIn a wide search program towards an efficient antibacterial, anti-inflammatory and analgesic agents, a series of 3,5-diaryl-1-phenyl-2-pyrazoline were synthesized starting from substituted α, β unsaturated carbonyl compounds which undergo cyclization reactions with phenylhydrazine. The synthesized compounds were characterized and confirmed on the basis of FT-IR, 1HNMR, 13CNMR and mass spectral data. The synthesized compounds 3,5-diaryl-1-phenyl-2-pyrazolines had shown significant activity against Staphylococcus aureus (MTCC 87), Escherichia Coli (MTCC 40), Pseudomonas aeruginosa (MTCC 424) and Proteus vulgaris (MTCC 426) by cup plate method using tetracycline-SD 037 as a reference standard. The anti-inflammatory property of 1,3,5-diaryl-1-phenyl-2-pyrazolines were screened by using carragenan induced paw edema method in Wistar rat. The compounds exhibited significant anti-inflammatory property further evaluated for analgesic activity using both acetic acid-induced abdominal writhing method and hot plate method respectively in Swiss albino mice. The anti-inflammatory and analgesic activities exhibited were comparable to that of the standard drug diclofenac. The safety of 3,5- diaryl-1-phenyl-2-pyrazolines were reflected by toxicity studies. EnglishChalcones; Pyrazolines; Antibacterial; Anti-inflammatory; Analgesic.INTRODUCTION Considerable interest has been focused on the pyrazoline structures, which are known to be biologically active and are important constituents of many pharmaceutical1 and agrochemical products2 . As a important class of biologically active agent pyrazoline possesses a broad spectrum of biological activities such as antibacterial3 , antifungal4 , antidepressant5 , antidiabetic6 , antiacetylcholinesterase7 , anti-inflammatory, analgesic8 , antiangiogenic and antioxidant9 . 2- pyrazoline being important nitrogen containing five member heterocyclic compounds seems to be the most frequently studied pyrazoline type compounds. With this background, it is considered worthwhile to synthesize 3,5- diaryl-1-phenyl-2-pyrazolines10 starting from simple condensation of substituted acetophenones with variously substituted aldehydes to give α, β unsaturated carbonyl compounds (2a-j) which undergo a subsequent cyclization reaction with phenylhydrazines affording 2-pyrazolines (3a-j) and screen them for antibacterial, anti-inflammatory and analgesic activities. The mass spectrum of 2a was recorded as additional evidence to the proposed structure. It exhibited molecular ion peak at m/z 208 corresponding to its molecular weight. The other predominant peaks, which were appeared at m/z 178, 105, 89, 77and 51 were in consistent with expected fragmentation pattern. The mass spectrum of 3a was recorded at m/z 298 corresponding to its molecular weight. The other predominant peaks, which were appeared at m/z 220, 180, 105 and 63 were in consistent with expected fragmentation pattern. The chalcones (2a-j) possessing α, β unsaturated ketone group, when reacted with phenylhydrazine underwent condensation and subsequent ring closure to give 2-pyrazolines (3a-j). The involvement of carbonyl group (C=O) in the reaction was indicated by the absence of absorption band at 1658 cm-1 and presence of a characteristic absorption band at 1597 cm-1 due to (C=N) stretching frequency of pyrazoline in the IR spectra of 3a.  Similarly chemical shift in 13CNMR reflected at δ 190.63 due to (C=O) group of 2a, which was absent in corresponding 2-pyrazoline rather represented at δ135.57 due to (C=N). The 1HNMR spectrum of 3a-j exhibited two doublets of doublets at δ 2.98-3.17, 3.79-3.95 and 5.20-5.67 due to Ha, Hb of (-CH2) and Hc of (-CH-) proton of 2- pyrazoline respectively. Multiplets were appeared due to aromatic protons with the expected chemical shift and integral value. In present study an attempt had been made to find out the efficiency of inhibition of bacterial growth in gram positive Staphylococcus aureus and gram negative Escherichia Coli, Pseudomonas aeruginosa and Proteus vulgaris, inflammation in Wister Albino rats and pain in Albino mice respectively .EXPERIMENTAL Melting points were determined in open capillary tubes are uncorrected. IR spectra were recorded on SHIMADZU FTIR affinity series-I using KBr. and 1HNMR spectra were recorded on BRUKNER AVANCE II 400 NMR SPECTROMETER using CDCl3 as solvent and TMS as an internal standard. Peak values are shown in δ ppm. Mass `2spectra were recorded on AGILENT gas chromatography-mass spectrometer. The purity of the synthesized compounds was checked by TLC on silica gel plates. added followed by the addition of substituted benzaldehydes (0.107M) and stirred for 1 hour. About 20ml of (10%) NaOH solution was added slowly to the stirred solution. The mixture was stirred for about 8-10 hours and kept in a deep freeze for an overnight. The solid products 1,3-diaryl prop-2-ene-1-one (2a-j) so formed were neutralized by hydrochloric acid. The products were filtered off and recrystalized by ethanol. After that in a 100ml round bottomed flask, to a solution of compounds (2a-j) (0.025M) in 20ml of glacial acetic acid equimolar of phenyl hydrazine (0.025M) was added, stirred for 1hours and refluxed for 5 hours. The mixtures were kept in deep freeze for an overnight. The solid products 3,5-diaryl-1-phenyl-2- pyrazolines (3a-j) so formed was neutralized by 2% sodium hydroxide solution.The product were recrytallized by ethanol. The completion of the reaction was monitored by TLC. METHODS Antibacterial activity The synthesized compounds were screened for in vitro antibacterial activity11 against gram-positive bacteria Staphylococcus aureus (MTCC 87) and gram-negative bacteria Escherichia Coli (MTCC 40), Proteus vulgaris (MTCC 426) and Pseudomonas aeruginosa (MTCC 424) by cup-plate method12 at a concentration 100 µg/ml in DMSO solution using tetracycline-SD 037 as a reference standard. Mueller–Hinton broth was used as medium for antibacterial activity. The Petri dishes were incubated at 36°C for 24 hours. Inhibition was recorded by measuring the diameter of the inhibition zone at the end of the 24hr. Each experiment was repeated duplicate and average of the two independent determinations was recorded. All the 2-pyrazoline compounds showed significant activity against these organisms.  Anti-inflammatory activity Animals Wistar Albino rats (150-200g) of either sex were used. The animals housed under standard laboratory conditions maintained at 25±1oC and under 12/12 hour light/dark cycle and fed with standard pellet diet (Gold Mohur brand, Lipton India limited.) and water ad libitum. The experimental protocols were approved by Institutional Animal Ethics Committee (Regn No: 926/ab/06/CPESEA). Acute toxicity study Acute toxicity of 3,5-diaryl-1-phenyl-2- pyrazoline derivatives were determined in Albino Wistar rats with the staircase method13. Each group of 6 animals was fasted for 24 hour prior to the administration of the test compounds. The test compounds, 3a-j were administered orally in doses up to 2000 mg/kg by suspending in 1% C.M.C solution and were kept under observation for period of 24 hour Carrageenan induced paw edema The anti-inflammatory activities14 of 3aj were assessed in vitro for their percent inhibition of paw edema in carrageen model of inflammation in albino wistar rats using the method illustrated by Winter et al15. After 16 hours of fast the rats were divided into different groups of six each. Carrageenan (0.1 mL, 1%) was administered into the plantar surface of the right hind paw of the animals. The experimental groups, negative control group (1% CMC), and positive control group (10 mg/kg/po of diclofenac sodium) were given either the control drug and test compounds orally, 1 hour prior to the administration of the carrageenan. Before injection of carrageenan, the average volume (Vo) of the right hind paw of each rat was calculated from 3 readings that did not deviate more than 3%. After injection of the phlogistic agent, the paw volume (Vt) was measured after 1st, 2nd, 3rd, 4th , and 5th hours respectively with the aid of a digital plethysmometer. The edema was expressed as an increase in the volume of paw and percentage inhibition of acute edema was obtained as follows: % inhibition = [1-(?V experimental/ ?V control)] x 100 Where, ?V = Vt-Vo = Mean paw volume Analgesic Activity Acetic acid induced writhing response (chemical) method The analgesic activities16 were assessed in vitro for their percent inhibition of nociception in acetic acid-induced abdominal writhing in Swiss albino mice using the method illustrated by Adeyemi  et al17. Vehicle, diclofenac sodium and test solution (20 mg/kg/po) were administered orally 30 min before the experiment and 0.1 ml per 10 g of 0.7% acetic acid saline was then injected i.p. 10 min after the injection. The number of writhing during the following 15 min period was counted. The antinociceptive activity will be expressed as percentage inhibition of abdominal writhing was calculated against the control on the basis of experimental data obtained. The pain inhibition percentage (%PIP) was calculated by % PIP = N−Nt / N x 100 N = Average number of stretching of control per group - Nt = Average number of stretching of test per group. Hot plate (Thermal) method The hot plate test performed using Eddy’s hot plate maintained at a temperature of 55±1.0 °C described by Turner 18 was used. The mice which showed fore or hind paw licking or jumping response withy in 6-8 secs were selected for the study. After 1 hr of administration of test and reference compounds, the animals of six groups were individually exposed to the hot plate maintained at 55±1.0 °C. A Cut-off period of 15 s was considered as maximal latency to avoid injury to the paws. The time taken by the animals to lick the fore or hind paw or jump out of the place was taken as the reaction time. Diclofenac sodium (20mg/kg/po) was used as a reference drug. The pain inhibition percentage (PIP) was Statistical Analysis: Percentage inhibition are expressed in mean ± SEM (n= 6 for each compound). The data were analyzed by One-Way ANOVA, at 99 % confidence interval, followed by Dunnett’s Multiple Comparison Test as post hoc analysis * p < 0.05 Significant Difference, ** p < 0.01 Significant, *** p < 0.001 Highly Significant compared to control and student t-test. DISCUSSIONS Antibacterial activity The antibacterial data indicated that the synthesized 3,5-diaryl-1-phenyl-2- pyrazolines (3a-j), showed significant antibacterial activity against  gram positive Staphylococcus aureus, moderate activity against gram negative Escherichia Coli, Proteus vulgaris and weak activity against Pseudomonas aerugenosa. It was to note that the compound (3j) carrying p-Br in two phenyl ring at C-3 and C-5 of pyrazoline moiety showed maximum activity followed by compound (3e) carrying pBr and p-Cl in phenyl ring at C-3 and C-5 respectively against all the strains. It was interesting to note that the substitution of electron withdrawing group p-Cl in phenyl at C-3 and electron donating group m,p-OCH3 in phenyl at C-5 led the compound (3h) found to be the good activity as compared to m,p-OCH3 substitution only in compound (3d)against all strains. Detailed antimicrobial activities were tabulated in table-1. Anti-inflammatory activity  Carrageenan-induced hind paw edema is the standard experimental model of acute inflammation. Carrageenan is the phlogistic agent of choice for testing anti-inflammatory drugs as it is not known to be antigenic and is devoid of apparent systemic effects. The carrageenan test was selected because of its sensitivity in defecting orally active anti-inflammatory agents particularly in the acute phase of inflammation. The percent inhibition of edema was calculated against the control on the basis of experimental data obtained. The percent inhibition was calculated from 1st hour to 5th hour as carrageenaninduced edema is a biphasic response. The first phase (0-3 hrs after injection of carrageenan) is mediated through the release of histamine, serotonin and kinins where as, the second phase is related to the release of prostaglandins and bradykinins. All the 3,5-diaryl-1-phenyl-2-pyrazoline derivatives exhibited encouraging antiinflammatory activity. The oral administration of different derivatives of 2-pyrazoline suppresses inflammation during the both the phase. The compounds showed ranging from 50.95% to 63.59% and 57.80% to 83.67% where as standard drug diclofenac showed 70.35% and 87.17% inhibition after 3rd and 5th hours respectively. Detailed anti-inflammatory activities had given in table-2. The anti-inflammatory activities data showed that compound (3h) having m,pOCH3 and p-Cl groups in the phenyl ring at C-5 and C-3 respectively of pyrazoline nucleus posses highest activity followed by compound (3d) having m,p-OCH3 group in the phenyl ring at C-5. It was noted in compounds (3b) and (3c) that the para substitution of electron with drawing groups of phenyl ring attached to C-3 in pyrazoline moiety shown lesser percentage of antiinflammatory activity. It was interesting to note that when both the phenyl rings at C-3 and C-5 substituted with electron with drawing groups showed significant anti-inflammatory activity. The low toxicity of synthesized compounds was evident from the observation that there was no mortality in rat at doses up to 2000mg/kg. Acetic acid induced writhing response The compounds showing significant anti-inflammatory activity were further screened for their peripheral analgesic activity. The anti-nociceptive activity will be expressed as percentage inhibition of abdominal writhing was calculated against the control on the basis of experimental data obtained. The percent inhibition was calculated after 30 minutes and it was found to be showing significant analgesic activity. Compounds showed analgesic activity ranging from 46.32% to 63.23%, where as standard drug diclofenac sodium showed 72.33% inhibition. It was observed that compound (3h) showing highest anti-inflammatory activity also exhibited highest analgesic activity 63.23% where as compound (3d) showed decrease in analgesic activity (%), although showed high antiinflammatory activity (%). All other compounds were found to have moderate analgesic activity. Detailed analgesic activities were tabulated in table-3. Hot plate method The compounds showing centrally acting analgesic activity generally elevate the pain threshold of mice towards heat. The highest nociperception of thermal stimulus was exhibited by compound (3h) PIP of 57.45% which is comparable to that of standard diclofenac PIP of 67.45%. Detailed analgesic activities were tabulated in table-4. It was observed that compounds (3e) and (3j) showed significant PIP activities which were earlier exhibited moderate peripheral analgesic activity. It was observed that compound (3d) although exhibited high anti-inflammatory activity (%) showed sharp decrease in analgesic activity (%).All other compounds were found to have moderate centrally acting analgesic activity. CONCLUSION The present study focused on potentially active skeleton of 2-pyrazolines. The antibacterial activity of different derivatives of 3,5-diaryl-1-phenyl-2- pyrazoline was investigated by means of cup plate method. It was found that electron with drawing groups (p-Br and/or p-Cl) attached to the phenyl ring at C-3 and C-5 of pyrazoline nucleus showed promising antibacterial activity and it was observed that the compounds 3j and 3e showed highest inhibitory activity against all strains of bacteria. The exact mechanism of action of antibacterial was not performed yet. The oral administration of different derivatives of 2-pyrazoline suppresses inflammation during the both the phase and mechanism of action probably or might be linked to lipoxygenase and/or cycloxygenase. The presence of electron donating group m,p-OCH3 at C-5 and electron with drawing group p-Cl at C-3 of phenyl ring of compound 3h showed maximum inhibitory response as compared to other derivatives and very nearer to standard drug diclofenac. The synthesized compounds had shown good anti-inflammatory were further subjected to analgesic activity and found to be good inhibitor of pain. The abdominal constrictions produced after administration of acetic acid is related to sensitization of nociceptive receptors to prostaglandins. It is therefore possible that the derivatives exert their analgesic effect probably by inhibiting the synthesis or action of prostaglandins. The centrally acting analgesics generally elevate the pain threshold of mice towards heat. In hot plate test 3,5-diaryl- 1-phenyl-2-pyrazolines showed significant pain inhibition percentage. It was interesting to know that the compound 3h which was found to be good anti-inflammatory agent also found to be good inhibitor of pain, which was comparable with the standard drug diclofenac. These synthesized drugs can be extended for further detailed study ACKNOWLEDGEMENT Authors are sincerely thankful to Principal and Head of Department of Pharmaceutical Chemistry of Roland institute of pharmaceutical sciences, Berhampur for providing necessary facilities to carrying out the research work. 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