Angiotensin-II receptor antagonists are a new class of drugs for the management of hypertension. The major obstacle to their development, i.e., poor oral bioavailability, seems to be solved as losartan and TCV-116 are non-peptide antagonists and orally effective. These agents are new and promising antihypertensives, better than angiotensin converting enzyme (ACE) inhibitors in controlling blood pressure. The antihypertensive effect of losartan is enhanced when given in combination with hydrochlorthiazide. Losartan is very well tolerated in patients with mild, moderate and severe hypertension. Losartan decreases the mean urinary protein excretion and may have a beneficial effect on albuminuria in patients with diabetes. The uricosuric effect of losartan may be beneficial as many hypertensive patients are hyperuricemic. Unlike with ACE inhibitors, the adjustment in losartan dosage is not needed in the patients with renal insufficiency. TCV-116, another angiotensin-II antagonist, is highly potent and long-acting. Apart from its antihypertensive effects, TCV-116 also prevented left ventricular hypertrophy induced by high fructose diet in spontaneously hypertensive rats. Results of the studies on losartan and other agents indicate that they would certainly acquire a commanding position in the treatment of hypertension.

The present study was undertaken to investigate the effects of testosterone, 17-( - estradiol and castration on serum alkaline phosphatase isoenzymes in male rats. Daily administration of testosterone (2 mg/kg) for 15, 30 and 60 days increased serum total alkaline phosphatase activity by 9, 26 and 65 percent respectively. Estradiol administration (0.2 mg/kg) in the same periods led to the increase of 69, 67 and 68 percent. Enzyme fractionation on sephacryl S-300 revealed that the increase in alkaline phosphatase activity was due to the absolute elevation of low-molecular weight alkaline phosphatase isoenzyme. Castration or treatment with actinomvcin-D puromvcin of the animal diminished enzyme activity bv 28-37 percent. The estradiol induced increase in enzymeactivity had additive effect with puromycin or actinomycin D in the doses used.

The influence of mint leaf and garlic oil, the two common ingredients of several digestive stimulant drugs, was examined on digestive enzymes of pancreas and intestinal mucosa and on bile secretion and composition in experimental rats. The test materials were ad-ministered orally at two doses which were either pharmacological dose or 5 times of this. The results indicated that mint leaf had significant stimulatory influence on lipase activity of pancreas and intestinal mucosa, while garlic oil stimulated the enzyme activity only in intestinal mucosa. Mint also stimulated intestinal amylase activity. Garlic oil exhibited a reduction in pancreatic trypsin and chymotrypsin activities. However, these test materials did not have any marked influence on bile secretion and composition.

The biochemical mechanism of anthelmintic action of palasonin the active principle of Butea frondosa seeds has been investigated on Ascaridia galli. Palasonin inhibited the glucose uptake and depleted the glycogen content in the presence of glucose indicating that palasonin affects the energy generating mechanism of the parasite. It also significantly increased the lactic acid suggesting inhibition of ATP production or accumulation of lactic acid. Palasonin had no effect on AChE activity, though it potentiated the spasmogenic effect of ACh on toad Rectus abdominis muscle. The frequency and magnitude of spontaneous contractions of A.galli were significantly inhibited by palasonin. Following 20 h incubation of A.gal li with palasonin, a significant inhibition in the gross visual motility was also observed. In conclusion, the possible mechanism of anthelmintic action of palasonin may be related to either inhibition of energy metabolism and/ or alteration in the motor activity of the parasite.

We studied the pattern of platelet aggregation in normal subjects as well as in patients of essential hypertension. Our study revealed that platelet aggregation was enhanced in hy-pertensive patients as compared to normal healthy volunteers. Both nifedipine (10 mg) and aspirin (75 mg) inhibited the platelet aggregation when administered alone or in combination both in hypertensive patients and in normal subjects. The combination of these two drugs might be of importance in routine use for essential hypertension for the combined effect of controlling the hypertension by nifedipine and inhibiting platelet aggregation by both nifedipine and aspirin.

An essential oil obtained from the herb of Santolina chamaecyparissus Linn. (Compositae) was evaluated for its antifungal activity against candidiasis. It was effective in controlling candidiasis both in vivo and in vitro. It also possessed antibacterial activity and the toxicity studies revealed the safety profile of the drug.

Exploration and locomotion was studied on a hole-board following intraperitoneal administration of CNS stimulants in mice. Each drug was studied at 3 dose levels after 5, 30 and 60 minutes of injection. Head-dip count in 5 min was taken as an index of exploration and squares crossed gave the locomotion score. All stimulant drugs significantly suppressed head dipping except caffeine (5 mg/kg) and leptazol (10 mg/kg). Locomotion was also decreased but to a variable degree except with amphetamine (2 and 4 mg/kg) and caffeine (10 and 20 mg/kg) which increased locomotor activity, and picrotoxin causing no significant change. The results reflect an anxiogenic profile of CNS stimulant drugs in animal model of anxiety with probable involvement of central dopaminergic system.

Diclofenac sodium 100 mg (2 x 50 mg enteric coated tablets) alone and in combination with rifampicin 600 mg as a single dose (group I and group II respectively) was administered to six healthy human volunteers in a cross over design. In the second study diclofenac sodium 100 mg was administered after a six day treatment with rifampicin 450 mg daily (Group Ill). Plasma concentrations of diclofenac were determined during a 8 hour period following drug administration. The mean peak plasma concentrations (Cmax) were 5.28, 6.68 and 2.99 fig/ml, time taken to reach. the peak (Tmax) were 3.17, 3.25 and 2.5 hrs and area under curve[AUC(0-()] were 14.17, 13.74 and 4.63 ug.hr/ml in the groups I, II and Ill respectively. Statistically a significant difference was observed in Cmax , AUC(0-() (P < 0.01) and Cl/f (P < 0.05) of diclofenac sodium when administered after six days treatment with rifampicin. However, there was no difference in pharmacokinetic parameters when diclofenac was administered with rifampicin as a single dose.

BR-l 6A, a herbal preparation, attenuates amnestic deficits induced by electroconvulsive shocks (ECS) in rats, In a study designed to test the cognition-protecting limits of BR-l 6A, adult, male, wistar rats (n = 28) preselected for slow learning on the Hebb Williams complex maze, received 6 once-daily ECS. Before (1 week), during (6 days) and after (1 week) the ECS course, the rats received (p.o) either BR-16A (200 mg/kg/day) or vehicle alone. Post-ECS, learning was assessed over 7 days on the complex maze. Hats receiving BR-l 6A performed significantly better than controls in both speed and magnitude of learning. The present experiment hence found no floor effect for BR-16A-mediated attenuation of ECS-induced anterograde amnesia.

A reversed phase high performance liquid chromatographic (RP HPLC) method was developed for the simultaneous determination of ampicillin and sulbactam in serum and aqueous humor. A mixture of acetonitrile and tetrabutyl ammonium hydrogen sulfate was used as mobile phase while caffeine was the internal standard. The assay was rapid, simple and allowed a good linear range of detection from 0.5 (g to 20 (g for ampicillin and 0.5 (g to 10 (g for sulbactam at 230 nm. The analysis was done on serum and aqueous humor samples collected after giving intramuscular injection of 1 gm of ampicillin and 500 mg of sulbactam 60-140 min prior to surgery in patients undergoing cataract surgery. The assay was also performed in pooled human serum samples separately and together. The results were statistically analysed for the viability of the assay procedure.

Pharmacokinetic parameters of lignocaine after synovial absorption during intra-articular bolus injection were studied. Local anaesthesia technique consisted of local infiltration and intra- articular bolus injection followed by continuous irrigation with adrenaline containing lignocaine solution. Total dose given was 7 mg/kg. Serum levels were measured during and following the procedure to determine peak levels obtained and to assure that toxic levels were not exceeded. Pharmacokinetic parameters determined were (mean ( SD) Cmax, Tmax, Ka and t1/2ab. Lignocaine levels ranged from 0.10 - 2.75 (g/ml with an average peak concentrations of 2.18 r 0.38 (g/ml. No complication of lignocaine toxicity was noted by the anaesthesiologist or the operating surgeon. Results indicated that injection of 7 mg/kg lignocaine intra- articularly during knee arthroscopy produced peak blood concentrations within the first hour of surgery and was considerably low to produce toxicity. This technique was safe well tolerated by all patients and found to be adequate by the surgeon.

Ethanol has been shown to contract isolated frog rectus abdominis in a dose-dependent manner and it has been suggested that acetylcholine (Ach) or Ach like neurotransmitter may be responsible for these contractions. To confirm it further, the present work was undertaken. Agents used in the study were hemicholinium, vecuronium and physostigmine. It was observed that hemicholinium (10-5M) inhibited ethanol induced contraction, suggesting action of ethanol through cholinergic mechanisms rather than a direct action. Vecuronium (10-5M) exhibited a non-competitive antagonism with ethanol, while physostigmine (10-5M) did not potentiate ethanol - induced contraction, suggesting that ethanol acts by release of Ach-like substance the nature of which needs to be determined

Non-enzymatic glycation seems to be one of the major contributory factors for the conformational loss in the lens proteins, and hence cause diabetic cataract. Here we made a trial to reduce non-enzymatic glycation of lens proteins by acidic amino acids. For this study we relied on the in vitro glycation of goat, rat and human cataractous lens proteins. Lens homogenates were incubated with different concentrations of glucose for 72 hours. The effects of 5 and 10 mM of aspartic acid and glutamic acid were studied individually. The observations of this study indicate that these two amino acids can protect lens proteins from glycation in vitro.

The effect of quinolones on skeletal muscle function was studied using cat tibialis anterior muscle-common peroneal nerve preparation. Screening of four quinolones viz. ciprofloxacin, norfloxacin, nalidixic acid and pefloxacin produced a decrease in nerve stimulation (NS) induced contractions similar to that seen with the positive controls (Gentamicin & streptomycin). Normal saline and penicillin (Negative controls) were devoid of any effect on neuromuscular junction. Periodic stimulation of nerve and muscle ruled out muscle tatigue as a cause of decrease in skeletal muscle function. Characterization of neuromuscular (NM) block by ciprofloxacin was carried out to determine action on postsynaptic site (Close intraarterial injection of ACh, reversal with neostigmine), Presynaptic site (Hemicholinium + high frequency stimulation, reversal with CaCl2) and muscle (continuous pancuronium infusion). Primary action of ciprofloxacin on motor end plate was suggested by no response to close intraarterial ACh and reversal with neostigmine. Action on presynaptic site as well as muscle possibly contributes to the action on NM junction. The results of the study suggest that quinolones probably have a weak curare like effect on NM junction similar to that of aminoglycosides.