Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241211EnglishN-0001November30General SciencesBACTERIOPHAGES: DISCOVERY AND THERAPEUTIC USES IN HUMANS AND ANIMALS English0308Pongsak RattanachaikunsoponEnglish Parichat PhumkhachornEnglishViruses are particles which can specifically infect many kinds of organisms such as bacteria, plants, animals and humans. These organisms are called host cells. Recently, bacteriophages, viruses specifically infecting bacteria, have become interesting to replace antibiotics to treat diseases in animals and humans caused by pathogenic bacteria infections. This article briefly describes about the discovery of bacteriophages, and their therapeutic uses in animals and humans. EnglishBacteriophage, bacteriophage therapy, discoveryINTRODUCTION A bacteriophage, or phage for its shortened name, is the collective name for viruses that infect bacteria. The name is derived from two words, bacteria and phagein (a Greek word for "to eat"). Generally, bacteriophages consist of an outer protein coat enclosing genetic material. The genomes of bacteriophages can be single stranded (ss) RNA, double stranded (ds) RNA, ssDNA or dsDNA between 5 and 500 kb long with either circular or linear arrangement. The phages, which are much smaller than their hosts, are usually between 20 to 200 nm in size. They are ubiquitous and can be found in all places populated by bacterial hosts such as soil, sea, food and gastro-intestinal tracts of animals and human. Although bacteriophages are infamous for their destructive activity against useful bacteria such as bacterial starter cultures used in fermented food industries, they show potentials to be used as an alternative way to kill pathogenic bacteria resistant to antibiotics. Recently, many research groups have tried to develop a new way of treatment based on bacteriophages which is called bacteriophage therapy for fighting animals and human diseases caused by multi drug resistant strains of many bacteria. Discovery of bacteriophages The history of bacteriophage discovery can be divided into two eras. The first era began in 1986. Ernest Hankin, a British bacteriologist observed the presence of antibacterial activity against Vibrio cholerae in the waters of the Gange and Jumna rivers in India[1]. He reported that an unidentified substance (which passed through fine porcelain filters and was heat labile) was responsible for this phenomenon. Later on, several investigators found evidence related to the finding of Hankin[2] . However, none of them further explored their findings until Frederick Twort, a British medically trained bacteriologist, reintroduced the subject almost twenty years after Hankin's observation by reporting a similar phenomenon and advancing the hypothesis that it may have due to a virus[3, 4]. However, he did not pursue his finding because of various reasons including financial difficulties. Felix d'Herelle, French-Canadian microbiologist at the Institute of Pasteur, Paris, was the most important person in the second era of bacteriophage discovery. Besides being the first man who used the word "bacteriophage", his works have been the strong foundation for modern researches on bacteriophages[5]. The first report of d"Herelle on bacteriophage phenomenon was in 1910 while he tried to develop microbiological means of controlling epizootic of locusts in Mexico. His work on bacteriophage continued until 1916 he proposed the name "bacteriophage" to call viruses capable of parasitizing bacteria. The name was formed from "bacteria" and "phagein" (to eat or devour, in Greek). In 1915, d'Herelle discovered plaques, although they were not initially called plaques. The discovery of plaques by d'Herelle was associated with an outbreak of hemorrhagic dysentery among French troops stationed at Maisons-Laffitte (on the outskirts of Paris) in 1915. Several soldiers were hospitalized, and d'Herelle was assigned to conduct an investigation of the outbreak. During this study, he made bacterium-free filtrates of the patients' fecal samples and mixed and incubated with Shigella strains isolated from the patient. A portion of the mixtures was inoculated into experimental animals and a portion was spread on agar medium in order to observe the growth of the bacteria. It was on these agar cultures that d'Herelle observed the appearance of small, clear areas, which he initially called taches, then taches vierges, and later, plaques. His findings were presented in the meeting of the Academy of Sciences in 1917[6] . History of bacteriophage therapy The first attempt to use bacteriophages therapeutically was conducted by d'Herelle. He used phages to treat dysentery at the Hopital des EnfantsMalades in Paris in 1919 under supervision of Professor Victor-Henri Huntinel, the hospital's Chief of Pediatrics[5]. The phage preparation was ingested by d'Herelle, Hutinel and several hospital interns in order to confirm its safety before giving it to a 12-year-old boy with severe dysentery. The patient's symptoms ceased after a single administration of the antidysentery phage, and the boy fully recovered within a few days. The efficacy of the phage preparation was confirmed shortly afterwards. Three patients suffered from bacterial dysentery started to recover within 24 h after taking a dose of the phage preparation. However, the results of these studied were not immediately published and, therefore, the first report of bacteriophage therapy against bacterial infected diseases in human came in 1921 from Richard Bruynoghe and Joseph Maisin[7]. They used bacteriophages to treat staphylococcal skin disease. Several similarly promising studies followed and encouraged by these early results[8-10] . Bacteriophage therapy in human The first report of application of phages to treat infectious diseases of human came from Bruynoghe and Maisin in 1912[7]. They used phages to treat staphylococcal skin disease. The phages were injected into and around surgically opened lesions and the regression of the infections was observed within 24 to 48 h. Phages have been used since that time for therapeutic purposes in the United States, in eastern Europe and in the former Soviet Union. The international literature contains several hundred reports on phage therapy, with the majority of the publications coming from researchers in the former Soviet Union and eastern European countries[11-13]. Phages have been reported to be effective in treating skin infections caused by Pseudomonas, Staphylococcus, Klebsiella, Proteus, and E. coli, staphylococcal lung and pleural infections[14, 15] . P. aeruginosa infections in cystic fibrosis patients[16] , neonatal sepsis[17], and surgical wound infections[18, 19]. The most detailed descriptions have come from the Institute of Immunology and Experimental Medicine of the Polish Academy of Sciences. Briefly, phage therapy was used on 550 patients, at 10 clinical and hospital departments in three different cities (Wrozlav, Lubin, and Kamienna Gora). The major infecting agents included Staphylococcus, Pseudomonas, Escherichia, Klebsiella, and Salmonella species. Phages were administered orally, applied directly to wounds, or given in eye drops. Reported success rates ranged from 75 to 100%, depending on the pathogen[20-26] . Recently, many strains of multi drug resistant bacteria have been discovered. Patients infected by these bacteria can be no longer treated with antibiotics. Bacteriophage therapy may be the answer for the diseases. The researches on bacteriophage therapy against multi drug resistant bacteria have been growing. In the future, many phage preparations will be come out to the public as new weapons for fighting the diseases that cannot be cured by antibiotics. Bacteriophage therapy in animals Many reports on bacteriophage therapy in animals have been published in scientific literature. One of the most detailed reports of the use of phages in veterinary medicine came from Smith and Huggin. In one of their early papers published in the Journal of General Microbiology, they reported the successful treatment of experimental E. coli infections in mice using phages and claimed the advantages of phage therapy or antibiotics[27]. They also conducted experiments using phages to reduce diarrheagenic E. coli in the alimentary tracts of calves, lambs and piglets. In addition, they showed that diarrhea could be prevented in calves by simply spraying the litter in the calf rooms with an aqueous phage suspension[28, 29]. A group of investigators in England successfully used phages to prevent and treat experimental infections with Psuedomonas aeruginosa and Acinetobacter in mice and guinea pigs[30]. There was also a report of using Salmonella and E. coli phages to prevent death of experimentally infected chickens[31]. Examples mentioned above are a very small fraction of works on bacteriophage therapy in animals. The researches on the issue are increasing and they will be in this direction for many years ahead. CONCLUSION Much of the evidence presented in this review strongly shows that phage therapy is very effective for treatment and prevention of many kinds of bacterial infectious diseases. Currently, many pathogenic bacteria have acquired multiple drug resistance, which is a serious clinical problem. Future trend of the research concerning phage therapy will be associated with the use of phages to control diseases caused by the multiple drug resistant pathogenic bacteria. However, phage therapy still has some problems remained to be solved including (1) inactivation of administrated phages by immune response of the treated organisms, (2) appearance of mutants to phages and (3) transfer of bacterial antibiotic resistant genes by phages. Finding of solutions for these problems are also the hot issues for future research about phage therapy. Englishhttp://ijcrr.com/abstract.php?article_id=2209http://ijcrr.com/article_html.php?did=22091. Hankin EH. L'action bactericide des eaux de la Jumna et du Gange sur le vibrion du cholera. Ann Inst Pasteur 1896; 10: 511. 2. Van Helvoort T. Bacteriological and physiological research styles in the early controversy on the nature of the bacteriophage phenomenon. Med Hist 1992; 3: 243-270. 3. Twort FW. An investigation on the nature of ultramicroscopic viruses. Lancet 1915; 2: 1241-1243. 4. Twort FW. Researches on dysentery. Br J Exp Pathol 1920; 1: 237-243. 5. Summers WC. Felix d'Herelle and the origins of molecular biology. New Haven: Yale University Press, 1999. 6. D'Herelle F. Sur un microbe invisible antagoniste des bacilles dysentériques. C R Acad Sci 1917; 165: 373-375. 7. Bruynoghe R, Maisin J. Essais de thérapeutique au moyen du bacteriophage. C R Soc Biol 1921; 85: 1120-1121. 8. Rice TB. Use of bacteriophage filtrates in treatment of suppurative conditions: report of 300 cases. Am J Med Sci 1930; 179: 345-360. 9. Schless RA. Staphylococcus aureus meningitis: treatment with specific bacteriophage. Am J Dis Child 1932; 44: 813-822. 10. Stout BF. Bacteriophage therapy. Texas State J Med 1933; 29: 205- 209. 11. Abdul-Hassan HS, El-Tahan E, Massoud B, Gomaa R. Bacteriophage therapy of pseudomonas burn wound sepsis. Ann Medit Burn Club 1990; 3: 262- 264. 12. Lang G, Kehr P, Mathevon H, Clavert JM, Sejourne P, Pointu J. Bacteriophage therapy of septic complications of orthopaedic surgery. Rev Chir Orthop Reparatrice Appar Mot 1979; 1: 33- 37. 13. Vieu JF, Guillermet F, Minck R, Nicolle P. Donnees actuelles sur les applications therapeutiques des bacteriophages. Bull Acad Natl Med 1979; 163: 61. 14. Cislo M, Dabrowski M, WeberDabrowska B, Woyton A. Bacteriophage treatment of suppurative skin infections. Arch Immunol Ther Exp 1987; 2: 175- 183. 15. Stroj L, Weber-Dabrowska B, Partyka K, Mulczyk M, Wojcik M. Successful treatment with bacteriophage in purulent cerebrospinal meningitis in a newborn. Neurol Neurochir Pol 1999; 3: 693-698. 16. Shabalova IA, Karpanov NI, Krylov VN, Sharibjanova TO, Akhverdijan VZ. Pseudomonas aeruginosa bacteriophage in treatment of P. aeruginosa infection in cystic fibrosis patients. Proc IX Int Cyst Fibrosis Congress 1995; 443. 17. Pavlenishvili I, Tsertsvadze T. Bacteriophagotherapy and enterosorbtion in treatment of sepsis of newborns caused by gramnegative bacteria. Pren Neon Infect 1993; 11 104. 18. Peremitina LD, Berillo EA, Khvoles AG. Experience in the therapeutic use of bacteriophage preparations in suppurative surgical infections. Zh Mikrobiol Epidemiol Immunobiol 1981; 9: 109 -110. 19. Pokrovskaya MP, Kaganova LC, Morosenko MA, Bulgakova AG, Skatsenko EE. Treatment of wounds with bacteriophages. 2nd ed. Moscow: State Publishing House, 1942. 20. Slopek S, Durlakowa I, WeberDabrowska B, KucharewiczKrukowska A, Dabrowski M, Bisikiewicz R. Results of bacteriophage treatment of suppurative bacterial infections. I. General evaluation of the results. Arch Immunol Ther Exp 1983; 31: 267-291. 21. Slopek S, Durlakowa I, WeberDabrowska B, KucharewiczKrukowska A, Dabrowski M, Bisikiewicz R. Results of bacteriophage treatment of suppurative bacterial infections. II. Detailed evaluation of the results. Arch Immunol Ther Exp 1983; 31: 293-327. 22. Slopek S, Durlakowa I, WeberDabrowska B, Dabrowski M, Kucharewicz-Krukowska A.Results of bacteriophage treatment of suppurative bacterial infections. III. Detailed evaluation of the results obtained in a further 150 cases. Arch Immunol Ther Exp 1984; 32: 317-335. 23. Slopek S, Kucharewicz-Krukowska A, Weber-Dabrowska B, Dabrowski M. Results of bacteriophage treatment of suppurative bacterial infections. IV. Evaluation of the results obtained in 370 cases. Arch Immunol Ther Exp 1985; 33: 219 - 240. 24. Slopek S, Kucharewicz-Krukowska A, Weber-Dabrowska B, Dabrowski M. Results of bacteriophage treatment of suppurative bacterial infections. V. Evaluation of the results obtained in children. Arch Immunol Ther Exp 1985; 33: 241- 259. 25. Slopek S, Kucharewicz-Krukowska A, Weber-Dabrowska B, Dabrowski M. Results of bacteriophage treatment of suppurative bacterial infections. VI. Analysis of treatment of suppurative staphylococcal infections. Arch Immunol Ther Exp 1985; 33: 261-273. 26. Slopek S, Weber-Dabrowska B, Dabrowski M, KucharewiczKrukowska A. Results of bacteriophage treatment of suppurative bacterial infections in the years 1981-1986. Arch Immunol Ther Exp 1987; 35: 569-583. 27. Smith HW, Huggins RB. Successful treatmcnt of experimental E.coli infection in mice using phage : its general superiority over antiobiotic. J Gen Microbiol 1982; 128: 307- 318. 28. Smith HW, Huggins RB. Effectiveness of phage in treating experimental E.coli diarrhea in calves, piglets and lambs. J Gen Microbiol 1983; 129: 2659-2675. 29. Smith HW, Huggins RB. The control of experimental E.coli diarrhea in calves by means of bactriophage. J Gen Microbiol 1987; 133: 1111-1126. 30. Soothill JS. Treatment of experimental infections of mice with bacteriophage. Med Microbiol 1992; 340: 258-261. 31. Berchieri A Jr, Barrow PA, Lovell MA. The activity in the chicken alimentary tract of bacteriophages lytic for Salmonella typhimurium. Res Microbiol 1991; 142: 541-549.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241211EnglishN-0001November30HealthcarePERFORMANCE ACCELERATING PARAMETER FOR MEDICAL REPRESENTATIVE English0913P. K. SahooEnglish MahendraEnglishThe study emphasize on finding various parameters which enhance the working efficiency of sales executive as these executive are the basic unit of the company to achieve the sales – backbone of the Business. Various motivational factors were identified by the literature survey and study conducted on the employees of various organizations and then these factors were correlated by the various hypotheses proposed e.g. Maslow's Hierarchy of Need Theory, Top Down Theory etc. Questionnaires used as a tool to study the various factors. Responses collected were analyzed and correlated by demographics. The motivational factors were found to be significantly affected by age and gender. EnglishTarget, Territory, Pharmaceutical Product ExecutiveINTRODUCTION Pharmaceutical product executives are the employee of pharmaceutical companies, responsible for the sales and building the image of the organization. Marketing executives are the key contacts between the pharmaceutical industry and the medical professionals. They have the responsibility of promoting their companies major products directly to GP's and hospital doctors. They do this via face to face meetings or medical presentations at various types of meetings. All representatives tend to work in a 'territory'. In terms of the marketing theory a territory is defined as a geographical area consisting of a sizable number of customers catered by a single marketing executive. Sometimes companies have double manned territories rather than single manned territories. The territory size, geography etc varies according to companies. The day to day work of the representative tends to be target based around, sales, call rates and other objectives set around individual personal development plans. The marketing executive takes care of the growth of sales of his territory, attends to the complaints of the distributors, retailers and customers. The marketing executive is responsible for collection of data and provides the same to the organization for further market research. Various functions of these employees are: 1. Giving presentations to doctors and various other medical staff. 2. Working with a sales team to develop strategies to approach potential customers and garner sales. 3. Working to meet and talk to new contacts within the healthcare field. 4. Keeping detailed records of all contacts, both potential and existing. 5. Organizing presentations and conferences for doctors and various other medical staff. 6. Staying up to date with the latest clinical data and passing this information on to healthcare professionals at presentations. 7. Cold-calling doctors, pharmacists, and other medical staff to setup appointments. 8. Keeping informed about the latest competitors' products. 9. Increase your company's brand and product awareness amongst healthcare professionals, and ultimately persuade them to adopt their usage. The Bottom Up Theory and Top Down Theory: Bottom up theory state that individuals have needs and they will be happy if their needs are satisfied. The sum of positive and negative effect is used to determine happiness. If positive effect is greater than negative effect, individual will judge their life as happy. In contrast, Top down theory states that there is a global propensity to experience things in a positive way. In other words, all individuals have a desire to be happy and this attitude will be the major influence on their lives. Thus, feeling about job satisfaction are generated in one of two ways: bottom up theory by adding positive effects and subtracting negative one's, or from the top down theory by the diffusion of one's desire to happy.3 Method: Questionnaire was prepared, aspects selected by literature review and consulting medical representatives of various organizations. Factors included are listed below: a) Increase in salary b) Recognition at work place c) Liberty to work d) Incentive e) Opportunity to personal growth f) Promotion g) Promotional scheme h) On the job training i) Meeting with superiors Job security j) Relationship with superior, peers and subordinates k) Self esteem Factors given in various question to rank them according to the priority of individual in different questions. In addition to above factor ranked some qualitative questions were also included i.e. Demotivational practice, Reason for leaving last organization. Data Collection: Data were collected personally at various hospital in delhi e.g. All India Institute of Medical Sciences, Safderjung Hospital, Batra hospital etc. Few were send by e mail for collecting responses. Sample: Sample size selected was 200, concerning the partially filled questionnaire total 220 questionnaire were distributed. Demographics: To study the impact of demographic factors on motivational factors some demographic factors were included in questionnaire i.e Age, Gender, Educational Qualification of respondents. The study included: RESULTS On the Basis of Age What are the motivational factor to you, which helps you to enhance your performance The number of respondents were 49 for increase in salary, 34 for Recognition at work place, 13 for Liberty to work, 14 for Incentive, 37 for Opportunity to personal growth, 18 for Promotion for the age group of 20 - 30 yrs and for the age group of 30 and above the number of respondents are, 12 for increase in salary, 6 for Recognition at work place, 4 for Liberty to work, 2 for Incentive, 7 for Opportunity to personal growth, 4 for Promotion. How the under mentioned activity motivates your target achievement The number of respondents were 75 for promotional scheme, 57 for On the job training, 33 for meeting with superiors for the age group of 20 - 30 yrs, the number of respondents for the age group 30 and above, 13 for promotional scheme, 18 for on the job training and 4 for meeting with superiors. The important factor for you for working in organization The number of respondents are 72 for job security, 38 for relationship with superior, peer and subordinate and 55 for self esteem for the age group of 20- 30yrs, and for the age group 30yrs and above 13 respondents were for job security, 12 for relationship with superior , peer and subordinate and 10 for self esteem. On basis of company profile What are the motivational factor to you, which helps you to enhance your performance The number of respondents from the Indian employee were 32 for increase in salary, 28 for recognition at work place, 12 for liberty to work, 9 for incentive, 26 for opportunity to personal growth and 18 were for promotion while employees from M.N.C the responses were, 27 increase in salary, 13 recognition at work place, 4 liberty to work , 6 incentive, 18 opportunity to personal growth and 7 for promotion. How the under mentioned activity motivates your target achievement The number of respondents were 55 for promotional scheme, 44 for on the job training and 26 for meeting with superiors for the employees of Indian organization, while for M.N.C. for, respondents were 32 for promotional scheme, 31 for on the job training and 12 for meeting with superiors The important factor for you for working in organization The number of respondents were 53 for job security, 33 for relationship with superior, peer and subordinate for Indian organization while for M.N.C. the respondents were 31 for job security, 22 for relationship with superior, peer and subordinate and 22 for self esteem DISCUSSION For the age group of 20 -30 yrs: In response to motivational factor necessary for them to increase the performance 29.69% respondents give their priority to increase in salary, For achieving the targeted sale 45.45% respondents find promotional schemes given to the chemist, Necessary factor for working in any organization priority given to job security 37.14%, For the age group 30 yrs and above respondent: They gave priority to increase in salary 34. 38%, In response to achievement of targeted sale 51.42% respond to on the job training, Respondent finds 37.14% self esteem as the important factor for you for working in organization. For executive from Indian company: The executives working for Indian company give their preferences to increase in salary 25.6%, they finds that promotional scheme given to chemist are more beneficial 42.4%, %, the factor necessary for them to work in organization jobs security 24.8%. For executive from M.N.C: The executive from Multinational Organization give their preference to increase in salary 36%, for achievement of targeted salary they find promotional scheme 42.67, %, the necessary factor for them to work in any organization are job security 42.34%. Englishhttp://ijcrr.com/abstract.php?article_id=2210http://ijcrr.com/article_html.php?did=22101. http://www.prospects.ac.uk/p/types _of_job/medical_sales_representati ve_job_description.jsp/ accessed on 10 Jan 2010 2. Prasad L M. Principle and practice of management.7th New Delhi. Sultan chand. P 661 3. Sharon A. Devaney, Zhan(Sandy) Chan. Job satisfaction of Recent Graduate in Financial Services. 2003 May 28.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241211EnglishN-0001November30Healthcare1,3,4-THIADIAZOLE AS ANTIINFLAMMATORY AGENT:A REVIEW English1426Mehnaz KamalEnglish Ashok K ShakyaEnglish Talha JawaidEnglish1,3,4-Thiadiazole nucleus exhibited remarkable pharmacological activities. Literature indicates that compounds having 1,3,4-Thiadiazole nucleus have wide range of pharmacological activities that include antibacterial, antifungal, antitubercular, antiviral, antileishmanial, anti-inflammatory, analgesic, CNS depressant, anticonvulsant, anticancer, antioxidant, antidiabetic, molluscicidal, antihypertensive, diuretic. The present review provides a broad view of the anti-inflammatory activity possessed by compounds having a 1,3,4-Thiadiazole nucleus. EnglishReview; 1,3,4-Thiadiazole; Chemistry; anti-inflammatory ActivityIntroduction One of the main objectives of organic and medicinal chemistry is the design, synthesis and production of molecules having value as human therapeutic agents. During the past decade, combinatorial chemistry has provided access to chemical libraries based on privileged structures [1], with heterocyclic structures receiving special attention as they belong to a class of compounds with proven utility in medicinal chemistry [2]. There are numerous biologically active molecules with five membered rings, containing three hetero atoms. Thiadiazole is an important scaffold known to be associated with several biological activities (Fig.1.). Chemistry of 1,3,4-Thiadiazole Thiadiazole is a five membered heterocyclic compound. It contains two nitrogen atoms and one sulphur atom as hetero atoms. Thiadiazole may be of 1,2,3- thiadiazoles (a) ; 1,2,4- thiadiazole (b) ; 1,3,4-thiadiazole (c) and 1,3,5-thiadiazole (d). Anti-inflammatory properties: Nonsteroidal anti-inflammatory drugs (NSAIDs) are an inhomogeneous family of pharmacologically active compounds used in the treatment of acute and chronic inflammation, pain, and fever. The inhibition of prostaglandin E2 (PGE2) and nitric oxide (NO) production has been proposed as a potential therapy for different inflammatory disorders. Large amounts of NO may lead to tissue damage. In inflammatory diseases such as rheumatoid arthritis, excessive NO production by activated macrophages has been observed. Therefore, it would be interesting to develop potent and selective inhibitors of NO for potential therapeutic use. Kumar et al.(2008) synthesized a series of 1,3,4-thiadiazole derivatives of biphenyl-4-yloxy acetic acid (1) in order to obtain new compounds with potential anti-inflammatory activity, analgesic activity and lower ulcerogenic potential. All compounds were evaluated for their anti-inflammatory activity by the carrageenan induced rat paw edema test method. The compounds possessing potent antiinflammatory activity were further tested for their analgesic, ulcerogenic and antioxidant activities. Some compounds showed significant reduction in rat paw edema induced by carrageenan treatment. These compounds showed significant analgesic effect and at an equimolar oral doses relative to flurbiprofen were also found to be non-gastrotoxic in rats [3]. Amir et al.(2007) synthesized some 6- substituted-1,2,4-triazolo[3,4-b]-1,3,4- thiadiazole derivatives (2-3). The compounds were pharmacologically evaluated for their anti-inflammatory and analgesic potentials by known experimental models. Several of these showed significant activity. Very low ulcerogenic index was observed for potent compounds [4]. Amir et al.(2007) prepared several 3,6- disubstituted-1,2,4-triazolo-[3,4-b]- 1,3,4-thiadiazoles (4-5). These compounds were investigated for their anti-inflammatory, analgesic, ulcerogenic, lipid peroxidation, antibacterial and antifungal activities. Some of the synthesized compounds showed potent anti-inflammatory activity along with minimal ulcerogenic effect and lipid peroxidation, compared to those of ibuprofen and flurbiprofen. Some of the tested compounds also showed moderate antimicrobial activity against tested bacterial and fungal strains [5]. Goksen et al.(2007) synthesized 1,3,4- thiadiazoles containing 5-methyl-2- benzoxazolinones (6). Most of the compounds were exhibiting high activity in analgesic-anti-inflammatory field [6]. Hafez et al.(2008) synthesized novel spiro-thioxanthene-9',2- [1,3,4]thiadiazoles and spiro-xanthene- 9',2-[1,3,4]thiadiazoles (7). The newly synthesized compounds were tested for anti-inflammatory and analgesic activities comparable to ibuprofen. Some of the compounds showed significant activity compared to standard drug [7]. Kadi et al.(2007) synthesized novel 2- (1-adamantyl)-5-substituted-1,3,4- oxadiazoles and 2-(1 adamantylamino)- 5-substituted-1,3,4-thiadiazoles (8). The in vivo anti-inflammatory activity of the synthesized compounds was determined using the carrageenin-induced paw edema method in rats. The oxadiazole derivatives produced good dosedependent anti-inflammatory activity [8]. Jadhav et al.(2008) synthesized a series of 6-substituted and 5,6-disubstituted 2- (6-methyl-benzofuran-3-ylmethyl)- imidazo[2,1-b][1,3,4]thiadiazoles (9). The new compounds have been tested for their in vivo analgesic, antiinflammatory activities. Qualitative SAR studies indicate that the chloro substitution in the imidazole ring and introduction of formyl group at C-5 position of the imidazole ring increased the anti-inflammatory and analgesic activity [9]. Hafez et al.(2008) synthesized novel spiro-thioxanthene-9',2- [1,3,4]thiadiazoles and spiro-xanthene- 9',2-[1,3,4]thiadiazoles (10). Some of the newly synthesized compounds were tested for anti-inflammatory and analgesic activities comparable to ibuprofen. Most of the compounds showed significant activity compared to standard drug [10]. Schenone et al.(2006) synthesized two series of N-[5-oxo-4-(arylsulfonyl)-4,5- dihydro-1,3,4-thiadiazol-2-yl]-amides (11) and tested in vivo for their analgesic and anti-inflammatory activities. All the new compounds possess good antalgic action in the acetic acid writhing test and some terms of the series showed also fair antiinflammatory activity in the carrageenan rat paw edema test [11]. Amir and Kumar(2004) synthesized new 1,3,4-thiadiazoles derived from 2- [(2,6-dichloroanilino) phenyl] acetic acid (12). These compounds were tested in vivo for their anti-inflammatory activity. Some compounds showed very good anti-inflammatory activity in the carrageenin induced rat paw edema test, with significant analgesic activity in the acetic acid induced writhing test together with negligible ulcerogenic action. The compounds, which showed less ulcerogenic action, also showed reduced malondialdehyde content (MDA), which is one of the byproduct of lipid peroxidation [12]. Gadad et al.(2008) synthesized a series of 2-trifluoromethyl/sulfonamido-5,6- diarylsubstituted imidazo[2,1-b]-1,3,4- thiadiazole derivatives (13-14). The selected compounds were evaluated for their preliminary in vitro cyclooxygenase inhibitory activity against COX-2 and COX-1 enzymes using colorimetric method. The compounds tested showed selective inhibitory activity toward COX-2 (80.6-49.4%) over COX-1 (30.6-8.6). These compounds also exhibited significant anti-inflammatory activity (70.09-42.32%), which is comparable to that of celecoxib in the carrageenaninduced rat paw edema method [13]. Palaska et al.(2002) synthesized 2-(2- naphthyloxymethyl)-5-substituted amino-1,3,4-thiadiazole derivatives (15) and evaluated as orally active antiinflammatory agents with reduced sideeffects. The anti-inflammatory and ulcerogenic activities of the compounds were compared with naproxen, indomethacin and phenylbutazone. In carrageenan-induced foot pad edema assay some compounds showed an interesting anti-inflammatory activity. Side effects of the compounds were examined on gastric mucosa, liver and stomach and none of the compounds showed significant side effects compared with reference nonsteroidal anti-inflammatory drugs (NSAIDs) [14]. Amir et al.(2007) synthesized some 6- substituted-1,2,4-triazolo[3,4-b]-1,3,4- thiadiazole derivatives (16-17) by cyclisation of 4-amino-5-[1-(6- methoxy-2-naphthyl)ethyl]-3-mercapto- (4H)-1,2,4-triazole with various substituted aromatic acids and aryl/ alkyl isothiocyanates. The compounds were evaluated for their antiinflammatory and analgesic potentials by known experimental models. Several of these showed significant activity [15]. Bhati and Kumar(2008) synthesized various N-({5-[(arylmethylene)amino]- 1,3,4-thiadiazol-2-yl}methyl) [1,3,4] thiadiazino[6,5-b]indol-3-amine (18), 2- aryl-3-{5-[([1,3,4] thiadiazino[6,5- b]indol-3-ylamino)methyl]-1,3,4- thiadiazol-2-yl}-1,3-thiazolidin-4-one (19) and 3-chloro-4-aryl-1-{5- [{[1,3,4]thiadiazino[6,5-b]indol-3- ylamino]methyl]-1,3,4-thiadiazol-2- yl}azetidin-2-one (20). One compound has shown most active antiinflammatory and analgesic activities with better ulcerogenic activity than phenylbutazone, while this compound was found to be associated with lesser degree of anti-inflammatory and analgesic activities as compared to indomethacin [16]. Bekhit et al.(2008) synthesized some thiazolyl and thiadiazolyl derivatives of 1H-pyrazole (21-22). All the target compounds showed anti-inflammatory activity and three of them surpassed that of indomethacin both locally and systemically in the cotton pellet granuloma and rat paw edema bioassay.[17]. Schenone et al.(2001) synthesized two series of 3-arylsulphonyl-5-arylamino- 1,3,4-thiadiazol-2(3H)ones (23) with potential anti-inflammatory and analgesic activity. Pharmacological results revealed that all the title compounds possess good antalgic activity and fair anti-inflammatory properties [18]. Rostom et al.(2009) described the synthesis of two groups of structure hybrids comprising basically the antipyrine moiety attached to polysubstituted 2,5-disubstituted-1,3,4- thiadiazole (24-25) through various linkages. The newly synthesized compounds were evaluated for their anti-inflammatory activity using two different screening protocols; namely, the formalin-induced paw edema and the turpentine oil-induced granuloma pouch bioassays, using diclofenac Na as a reference standard. Meanwhile, the analgesic activity of the same compounds was evaluated using the rat tail withdrawal technique. In general, compounds belonging to the thiazolylantipyrine series exhibited better biological activities than their thiadiazolyl structure variants [19]. Kumar et al.(2008) synthesized a series of 1,3,4-thiadiazole derivatives of biphenyl-4-yloxy acetic acid (26) in order to obtain new compounds with potential anti-inflammatory activity, analgesic activity and lower ulcerogenic potential. The compounds possessing potent anti-inflammatory activity were further tested for their analgesic, ulcerogenic and antioxidant activities. Out of all tested compounds, the some compounds showed significant reduction in rat paw edema induced by carrageenan treatment [20]. Mathew et al.(2007) synthesized several 3,6-disubstituted-1,2,4- triazolo[3,4-b]-1,3,4-thiadiazole and their dihydro analogues (27). Antiinflammatory and analgesic activity screening indicated that some of the tested compounds showed good and some showed moderate antiinflammatory and analgesic activities [21]. Sharma et al.(2008) synthesized a new series of cyclooxygenase-2 inhibitors with 2-amino- -5-sulfanyl-1,3,4-thiadiazole (28) as the central scaffold unit. Some compounds exhibited significant biological activity [22]. Amir and Kumar(2007) synthesized various 1,3,4-thiadiazoles derivatives of ibuprofen (29). The cyclized derivatives were screened for their antiinflammatory activity by the carrageenan induced rat paw edema method and showed 50 to 86% inhibition, whereas the standard drug ibuprofen showed 92% inhibition at the same oral dose [23]. Mishra et al.(1992) synthesized new Nsubstituted acetyl derivetives of 2- amino-5-alkyl-1,3,4-thiadiazoles (30) and evaluated for anti-inflammatory activity. 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