Initial discovery of nalidixic acid (a naphthyridine) was followed by synthesis and development of related compounds like pyridopyrimidine, cinnoline and quinolones, etc. Many of them were marketed long before the molecular basis of their action was elucidated in terms of DNA gyrase inhibition. Among these, nalidixic acid and fluoroquinolones had the greatest success. Fluoroquinolones available for clinical use over the past 10 years are norfloxacin, pefloxacin, ciprofloxacin, ofloxacin, enoxacin and lomefloxacin. with the addition of promising congeners under clinical development such as sparfloxacin, levofloxacin, clinafloxacin, grepafloxacin (OPC-17116), trovafloxacin (CP-99,219) and Du6859a. 2-Pyridones are the most recent addition to this array of DNA gyrase inhibitors emerging as antimicrobial wonder drugs. They have structural similarities with fluoroquinolones as regards position of carbonyl and carboxyl groups, or fluorine in the core, but are distinct in having a nitrogen (N) atom located at one of the two junctions of the two six-membered rings.This position of 'N' possibly makes 2-pyridones, as agents having exceptional breadth of spectrum, with remarkable action against DNA gyrase and topoisomerase-IV enzymes. A compound designated ABT-719 (also A-86719.1), which is a 2-pyridone, has been tested (in vitro) for its considerable activity against many gram positive and anaerobic infections and has been compared with ciprofloxacin in isolates for a greater gram negative activity. It also has been found to be effective against several systemic infections and the most challenging and troublesome vancomycin-, methicillin- and ciprofloxacin-resistant pathogens. However, 2-pyridones are in Phase II and Phase III clinical development, the outcome of which is awaited.

0bjective:To examine the haematological and biological changes induced by the toad skin extract (TSE) of the common Indian toad (Bufo melanostictus) in rodents. Methods:TSE was injected (SC) in male albino mice and rat (normal and splenectomized) and haemoglobin, haematocrit, RBC and WBC counts were done at different time intervals. Serum glucose, cholesterol, HDL-cholesterol, triglycerides, urea creatinine, iron, total iron binding capacity (TIBC), transaminase and phosphatase levels were also measured on TSE injected male albino rats. Results: TSE significantly decreased haemoglobin, haematocrit and total RBC count of male albino mice. However, it significantly increased total WBC, lymphocyte and monocyte count. In splenectomized rat, TSE showed no change on haemoglobin, haematocrit and total RBC count but increased total WBC and lymphocyte count. TSE also produced significant fall of serum glucose, cholesterol, triglyceride, urea and transminase levels and increased serum iron and TIBC level in male albino rats. Conclusion:TSE induced changes on haematological and biochemical parameters in rodents, indicated the toxic nature of TSE.This toxicity of TSE probably provides first line of defence in toad against predators.

Objective : To study the effect of S-allyl cysteine sulphoxide (SACS) in rats on atherogenic diet with monosodium glutamate. Methods : Rats on atherogenic diet with monosodium glutamate (MSG) at two doses received SACS for thirty days. At the end of thirty days malondialdehyde, hydroperoxide, conjugated diene and reduced glutathione content were estimated in the heart, liver, kidney, lung and brain. Super oxide dismutase (SOD) and catalase levels were analysed in heart, liver and kidney. Results : SACS significantly decreased the concentration of malondialdehyde, hydroperoxides and conjugated diene in liver and heart in rats treated on MSG (250 mgkg). There were no significant changes observed by SACS in rats on MSG (1g/kg) as well as effect of SACS on MSG (250mg/kg) in lungs, kidney and brain. Reduced glutathione (GSH), SOD and Catalase levels were increased in liver, kidney and heart in rats on SACS. Conclusion : SACS produces a significant antioxidant effect in atherogenic rats on lower dose of MSG.

Objective: To investigate the interaction of calcium channel blockers (CCBs) with noradrenaline (NA) and terbutaline (TA) in rat isolated right ventricle preparations. Methods: Ventricles were obtained from control rats, DOCA-saline hypertensive rats and hyperthyroid rats treated chronically with diltiazem, nifedipine or nimodipine. Responses of isolated ventricles to NA and TA were recorded on polyrite using force displacement transducer. Results: In control rats chronic treatment with diltiazem, nifedipine or nimodipine produced an increase in the pD2 value of NA and TA. In hypertensive rats there was an increase in the pD2 value of NA and TA with no change (NA) and increase (TA) in maxima. In chronic nifedipine or nimodipine treated hypertensive preparations the maximal responses to NA and TA were decreased with reduction of pD2 value of NA and no effect on that of TA. Microscopical observations of nifedipine treated hypertensive preparations produced restoration of the tissue damage to normal. There was increase in the pD2 value of both agonists in hyperthyroid preparations. Simultaneous treatment with L-thyroxine and CCBs produced decrease in pD2 values and maximal response to NA and no response to TA. Microscopical observation of hyperthyroid preparations treated with nimodipine produced normalization of the structure. Conclusion: In control preparations treated with CCBs down-regulation of beta, receptor may be associated with upregulation of beta, receptors. The beneficial effects of CCBs in hypertension and hyperthyroidism may be due to down-regulation of beta-adrenoceptors.

Objectives: To evaluate the effect of Serankottai Nei, a Siddha preparation of Semecarpus anacardium nut extract on adjuvant arthritis associated carbohydrates metabolic changes in albino rats. Methods: The drug was administered at a dose level of 150 mg/kg body weight for 14 days to arthritic animals after 14 days from the day of adjuvant injuction. At the end of the experimental period the glucose metabolizing enzymes (glycolytic and gluconeogenic) activities were studied in control, arthritis induced and drug treated groups. In addition transaminases activities and blood glucose levels were also analysed. Results: Significantly decreased activity of glycolytic enzymes with concomitant increase in the activities of gluconeogenic enzymes and blood glucose levels developed during arthritic condition were reverted back to near normal in drug treated animals. Conclusion: These observations suggest that the carbohydrate metabolism was significantly affected during arthritic condition and the Siddha drug,Serankottai Nei, may normalise it.

Objectives: To find the effects of ascorbic acid on immune system in rabbits and human volunteers. Methods: In humans, humoral immunity was measured by immunoglobulin estimation (IgG, IgM, IgA) using tripantigen plates and cell mediated immunity by total lymphocyte count and T-cell count. In rabbits, widal agglutination test using typhoid-H antigen and Dinitro chlorobenzene (DNCB) and tuberculin skin sensitivity tests were performed as measurement of humoral and cell-mediated immunity, respectively. Result: Administration of ascorbic acid 500 mg thrice daily orally for 21 days increased serum immunoglobulin in human subjects. In rabbits, ascorbic acid administration in the dose of 200 mg/kg/day orally for 21 days caused a rise in antibody titre. No effect on cell mediated immunity was found in human as well as animal models. Conclusion: Ascorbic acid appears to stimulate humoral immunity through increased antibody synthesis particularly IgG, IgA and IgM types and also by activating the macrophages.

Objectives: To evaluate the usefulness of Patient Oriented Problem Solving (POPS) method of teaching pharmacology and to compare its effect with teaching using audiovisual aids. Methods: The POPS session was evaluated using a pre-test and post-test. The pre-test gave an idea of the students' stored knowledge, whereas the post-test assessed memory retention and analytical skill. After a series of Audiovisual Aided (AVA) lectures, a multiple choice questions (MCQs) test to evaluate memory retention and a problem solving questions (PSQs) test on common clinical conditions to evaluate analytical skill were conducted. Results: In the POPS method, there was a significant improvement in the post-test scores over the pre-test scores showing that even without lectures, problem solving ability developed in students. On comparing the MCQs test scores with the POPS post-test scores, more students had scored higher in the MCQs test showing that memory retention was better after AVA lectures. On comparing the MCQs test scores with PSQs test scores, more students had scored higher in the MCQs test showing that after AVA lectures, memory retention was better than analytical skill. The scores obtained in the PSQs test and POPS post-test were also compared. There was no statistically significant difference between them showing that analytical skill developed in students by both methods of teaching. Conclusion: Teaching through AVA lectures positively influences both memory retention and analytical skill. POPS methods motivates self learning and develops analytical skill. The educative value of these two systems of teaching is complementary.

Objective: To investigate the suitability of toad large intestine for bioassay of cholinomimetics. Method: The effect of cholinomimetics, - ACh and carbachol (CCh) was determined using the isolated toad large intestine.The results were compared in parallel experiments using the isolated terminal guinea-pig ileum. In both preparations, equiconcentrations of agonists: 0.55, 1.1, 2.2, 4.4, X 10-6M were used and produced similar responses quantitatively. Similarly, equiconcentrations of atropine: 1.4, 2.9, 5.8, X 1 O-9M respectively produced the same degree and type of block in the two preparations. Results: The pA2 and pD2 values in the two preparations were similar and there was no significant difference between these values and those obtained in respect of the guinea-pig ileum by previous workers. The affinity constants, dissociation constants and the intrinsic activity values obtained for the cholinomimetics were the same in the two preparations and correspond to values previously reported by other workers. The sensitivity to ACh in the toad large intestine preparation was increased by physostigmine (0.36 x 10-5M) and compared favourably with results obtained by other workers using other biological preparations. Conclusion: Isolated toad large intestine can be used as an inexpensive alternative to the guinea-pig ileum in the bioassay of cholinomimetics.

Objectives: To investigate the role of GABA in the analgesia produced by the physical and psychological stressors in rats. Methods: Rats were exposed to physical stress (cold water swim stress) and psychological stress (fear) with and without the pretreatment of GABA synthesis inhibitor thiosemicarbazide (5 mg/kg ) in separate groups.Tail flick test was done using analgesiometer to assess the antinociceptive response. The analgesic response was measured as tail flick latency, recorded at the basal time, 10, 20 and 30 minutes duration of time intervals. The data obtained was compared with the control and between the groups. Results: Antinociceptive response was significant, as revealed, at the basal time measurement of tail flick latency, in the drug treated and drug free rats, exposed to the physical stress. Similar significance was also present in the drug free animals exposed to the psychological stress, while the group, which received GABA synthesis inhibitor and exposed to the psychological stress, did not show any significant antinociceptive response. Conclusion: In psychological stress induced analgesia GABA mechanism may be involved but it may not be involved in the analgesia produced by the physical stress.

Objectives: To investigate the role of GABA in the analgesia produced by the physical and psychological stressors in rats. Methods: Rats were exposed to physical stress (cold water swim stress) and psychological stress (fear) with and without the pretreatment of GABA synthesis inhibitor thiosemicarbazide (5 mg/kg ) in separate groups.Tail flick test was done using analgesiometer to assess the antinociceptive response. The analgesic response was measured as tail flick latency, recorded at the basal time, 10, 20 and 30 minutes duration of time intervals. The data obtained was compared with the control and between the groups. Results: Antinociceptive response was significant, as revealed, at the basal time measurement of tail flick latency, in the drug treated and drug free rats, exposed to the physical stress. Similar significance was also present in the drug free animals exposed to the psychological stress, while the group, which received GABA synthesis inhibitor and exposed to the psychological stress, did not show any significant antinociceptive response. Conclusion: In psychological stress induced analgesia GABA mechanism may be involved but it may not be involved in the analgesia produced by the physical stress.