Objective: The present study investigates the effects of various neorosteroids on hypoxic stress-induced neurotoxicity in naive and FG 7142-treated mice. Methods: The extent of neurotoxicity after the slow induction of hypoxic stress was estimated by measuring the latency for the onset of tremors and convulsions followed by death. Results: Treatment with FG 7142 (5-20 mg/kg, i.p.), a benzodiazepine (BZD) inverse agonist, augmented the hypoxic neurotoxicity. Pretreatment with neurosteroid allopregnanolone (AP) offered a significant protection in both naive and FG 7142- treated mice. Dehydroepiandrosterone sulphate (DHEAS) had no protective effect. In contrast, pregnenolone sulphate (PS) at high doses significantly protected naive but not FG 7142-treated mice, while low doses are ineffective. Progesterone (PROG), aneurosteroid precursor, and 4' chlordiazepam (4'-CD), a mitochondrial diazepam binding inhibitor receptor (MDR) agonist, produced a dose-dependent protection of both naive and FG 7142-treated mice. The neuro-protective effects of AP, PROG and 4'-CD against hypoxic neurotoxicity were blocked by picrotoxin, a GABA-A chloride channel antagonist, but not by flumazenil, a selective BZD antagonist. However, picrotoxin failed to reverse the PS-induced hypoxic neuroprotection. The 4'-CD elicited protection was, however, reversed by PK11195, a partial MDR antagonist. In addition, triazolam, a short acting BZD, nifedipine, a calcium channel blocker, and dizocilpine, a non-competitive NMDA receptor blocker, also dose-dependently protected the mice from hypoxic neurotoxicity. Combined exposure of nifedipine and PS resulted in a significant additive effect in protecting the hypoxic neurotoxicity. Similarly, combined administration of nifedipine with PROG, 4'-CD or dizocilpine markedly augmented the protective effect of nifedipine. Further, the dizocilpine induced neuroprotection was blocked by DHEAS. Conclusion: These results show that neurosteroids AP, PS and PROG, and MDR ligand 4'-CD possess neuroprotective activity in hypoxic stress models. Further, the present study suggests a role for GABA-A and mitochondrial DBI receptors in the neurosteroidal alleviation of hypoxic neurotoxicity, and thus may have therapeutic implications in cerebral ischemia and neurodegenerative disorders.

Objective: To study analgesic effects and safety aspects of traditional silver preparations: Raupya Bhasma, Kushta Nuqra and Chandi Warq. Methods: The investigations were carried out against four types of noxious stimuli: mechanical (tail clip), chemical (acetic acid-induced writhing), electrical (pododolorimeter) and thermal (Eddys hot plate and analgesiometer) in rats and mice. Effects following naloxone pre-treatment and maximum tolerated dose (MTD) were also studied. Results: Test drugs (25-50 mg/kg, p.o) exhibited analgesic activity against chemical, thermal and electrical stimuli but not against mechanical stimulus. The effects were reduced in naloxone pre-treated animals. The MTD was more than 2 g/kg, p.o. Conclusion: Test drugs exhibited moderate to marked analgesic effects with wide margin of safety. Involvement of opioidergic mechanism is suggested.

Objectives: To find the effect of a-tocopherol pretreatment on the lipid and lipoprotein profile after administration of isoproterenol in the doses which have been demonstrated to induce myocardial infarction in rats. Methods: The effect of a-tocopherol (6mg/100 g for a period of 90 days) pretreatment on isoproterenol (20mg/ 100g s.c., twice at an interval of 24h) induced changes in lipid and lipoprotein profile was studied in rats. Serum lipoproteins were separated by a dual precipitation method and cholesterol and triglycerides were estimated using standard established procedures. Lipid peroxides, lipoprotein lipase, triglyceride lipase, cholesterol ester synthetase and cholesterol ester hydrolase activities were estimated in heart homogenate. Total cholesterol, free cholesterol, triglycerides, phospholipid and free fatty acids were estimated in serum and heart. Results: A significant increase was observed in the levels of total cholesterol, ester cholesterol, triglycerides and free fatty acids in serum and heart of isoproterenol treated rats. The myocardial phospholipid content decreased significantly on isoproterenol administration. lsoproterenol administered rats showed a significant decrease in the activity of cholesterol ester hydrolase and lipoprotein lipase, whereas cholesterol ester synthetase and triglyceride lipase activity was observed to be increased. In isoproterenol administered rats, cholesterol and triglycerides in LDL and VLDL fractions increased significantly with a significant decrease in the HDL fraction. In rats pretreated with a-tocopherol, the alterations observed in the lipids, lipid metabolising enzymes and serum lipoproteins were minimum on isoproterenol administration, and the levels were retained at near normal values. Conclusion: The results obtained in the present study indicates that a-tocopherol pretreatment offers protection in experimental myocardial infarction induced by isoproterenol, by preventing lipid peroxidation and overloading of myocardium with lipids thus maintaining the structure and function of the myocardium.

Objective: To demonstrate the usefulness of fluorescence in situ hybridization(FISH) directed against monosomy 7 and 5q-, in early detection of therapy related acute myeloid leukemia (t-AML) in patients receiving cytotoxic chemotherapy. Methods: This is a retrospective study of five patients who developed t-AML/t-MDS after cytotoxic chemotherapy for primary malignant disorders. These patients underwent periodic cytogenetic work-up and the remaining samples were available for FISH analysis. Clinical and cytogenetic data concerning these patients were retrieved from the records of the Clinical Pathology Department. Sequential interphase FISH analysis with D7Z1 and 5q31.1 probe was performed as per standard protocols to detect the exact time of origin of these abnormalities. Results: FISH detected monosomy 7 and 5q-atleast 12-36 months before the onset of clinical manifestations in these patients. Conclusion: Molecular cytogenetic techniques can be of good use to clinical pharmacologists in early detection of t-AML in patients undergoing cytotoxic chemotherapy.

Objective: A pharmacy based prescription audit was undertaken in an Indian referral hospital to evaluate the feasibility of data acquisition methods and to determine the frequency of prescribing of antimicrobial drugs. An attempt was also made to relate prescription data to age and sex of patients. Methods: During the period of study 289 prescriptions of the patients admitted in the department of Internal Medicine were used for drug utilisation studies of antimicrobials. The analysis was done for the number of antimicrobials in each prescription, prescribed frequency of individual drug, number and dose unit prescribed (DDD), age and sex frequency. Attempt was made to correlate the usage of antimicrobials with culture and sensitivity test. Results: The frequency of prescribing penicillins and cephalosporins was 67.82%, tetracycline and chloramphenicol 4.84%, aminoglycosides 31.83%, vancomycin 1.03%, quinolones 34.25% and metro-nidazole 25.25%. The prescribing frequency of penicillins and cephalosporins was significant (P<0.01) in males while compared with females. Expensive antimicrobials like cephalosporins, quinolones and vancomycin were frequently prescribed without culture and sensitivity studies. Conclusion: There exists both need and feasibility to perform prescription audit analysis using the accepted methods of monitoring the utilization of drugs in an Indian hospital set up.

Objective: To study the effect of centrally administered prostaglandins and cyclooxygenase inhibitors on Brewer's yeast-induced peripheral inflammation and nociception. Methods: Intracerebroventricular (ICV) cannulation was performed in rats. Arachidonic acid, PGE2 PGF2( paracetamol. aspirin and indomethacin were administered centrally, before acute inflammation was Induced by Brewer's yeast. The hind paw oedema volume and pain threshold were measured by plethysmometer and analgesiometer, respectively. Results: PGF2( paracetamol, aspirin and indomethacin significantly suppressed the paw oedema volume at various periods of inflammatory process. Arachidonic acid and PGE2 reduced the pain threshold while, paracetamol and aspirin significantly augmented the pain threshold. Conclusion: Centrally administered PGF2( effect on Brewer's yeast-induced acute inflammation and pain, providing evidence of involvement of 29 exerts anti-inflammatory while, PGE2 exerts pronociceptive CNS in modulation of peripheral inflammation and pain.

Objective: To investigate the effectiveness of prazosin, a selective alpha-l adrenoceptor antagonist in the treatment of benign prostatic hyperplasia (BPH) in Indian population. Methods: Twenty six patients who had obstructive and irritative symptoms in addition to enlarged prostate assessed by Boyarsky symptom score, rectal examination, ultrasonography, uroflowmetry were included. Patients with urinary tract infections, diabetes mellitus, cerebrovascular, cardiovascular diseases and those taking medications known to influence vesicourethral functions were excluded. The patients were administered prazosin (prazopress) 0.5 mg in the morning and 0.5 mg at night in the first week and subsequently, 0.5 mg morning and 1 mg at night for another 3 weeks. Pretreatment and post-treatment assessment criteria were compared statistically using Student's 't' test. Results: Voiding symptoms, assessed on the basis of Boyarsky scale and micturition history; urinary flow rates measured by uroflowmeter were significantly improved (pc 0.001). Clinical safety was assessed by measurement of blood pressure, volunteered complaints and by questionnaire. At this dosage schedule the clinical safety was good. Conclusion: Prazosin is effective in the dose of 0.5 mg (morning) and 1 mg (night) in the treatment of patients with symptomatic BPH. The incidence of adverse events related to its vasodilator properties were minimal.

Objective: To investigate the hepatoprotective activity of ethyl acetate extract of Acacia Catechu, katha. Methods: The acute liver damage in albino rats was induced by a single subcutaneous administration of 4 ml/kg dose of 50% v/v of carbon tetrachloride in olive oil and the chronic liver damage by subcutaneous injection of 50% v/v carbon tetrachloride in olive oil at the dose of 2 ml/kg twice a week for 14 days. The hepatoprotective activity was monitored biochemically by estimating serum hansaminase, serum alkaline phosphatase and serum bilirubin in both the cases after intraperitoneal injection of ethylacetate extract of "katha" (250 mg/kg). The histopathological changes of liver samples were compared with that of control. Results: Ethyl acetate extract of "katha" inhibited carbon tetrachloride induced liver toxicity in albino rats at 250 mg/kg, b.w. as assessed by the biochemical and histopathological values. Conclusion: Ethyl acetate extract of "katha" exhibited significant hepatoprotective activity.

Objective: To study the effect of methylene blue on monkey aortic strips with intact and damaged endothelium. Methods: The monkeys were anaesthetised and a section of thoracic aorta was removed and cut into transverse strips. Vessels were suspended in a 10 ml organ bath containing Hanks physiological solution oxygenated with 100% oxygen. The tissues were equilibrated for 90 minutes under a resting tension of 3g. Isometric tensions were recorded with a force displacement transducer and recorded on a student physiograph. After the equilibration period, strips were used for relaxation studies. Results: In isolated monkey aortic strips, acetylcholine was found to cause relaxation in strips possessing intact endothelial cells. It produces contraction in strips with damaged endothelial cells. The percentage relaxation by acetylcholine in the absence of methylene blue in aortic strips with endothelium was 30.43 ( 8.3 and in the presence of methylene blue(an inhibitor of guanylate cyclase), the percent relaxation to acetylcholine was 9.05 ( 4.9. The contraction in damaged strips was enhanced in the presence of methylene blue. Conclusion: Methylene blue decreased the relaxation response to acetylcholine in monkey strips with intact endothelium. In strips with damaged endothelium, methylene blue increased the contraction caused by acetylcholine.

. Forty healthy individuals and 70 psychiatric patients aged 25 to 45 years without previous history of TAB inoculation or enteric fever during last one year and serum negative for S. typhi and S. paratyphi (A & B) antibodies (titre<40) were selected. Group of 40 healthy individuals served as control. The psychiatric patients were started on chlorpromazine 2.5 mg three times a day orally. On 7th day 1 ml of formalised TAB vaccine (Glaxo) was injected subcutaneously. Blood was with-drawn on 15th and 30th days of inoculation and serum was tested for antibody titre by agglutination. The antibody titre was significantly lower in the chlorpromazine treated group against TO and TH on 15th day and against PA (H) and PB (H) also on 30th day. The parallel shift of the curves in the treated group as compared to the control suggests that only one mechanism is likely to be responsible for the reduction in antibody titre. It is concluded that chlorpromazine produces a significant immunological inhibition when administered for 7 days prior to TAB vaccine.