: In an attempt to understand the mechanism of action of arecoline at molecular level, interaction of 3H arecoline with DNA, RNA, Protein in glutathione was studied in Swiss mice. Six week old Swiss strain male mice were injected (ip) with 3H arecoline (1 'ci/g body wt). Animals were killed at different time intervals (10 min, 3 h, 18 h 24 h, 7 days) after the injection. DNA, RNA, protein and glutathione were isolated by standard methods and radioactivity was measured from these fractions. Among all these fractions maximum specific activity was observed in glutathione fraction and next to it in DNA fraction Significantly high radioactivity was observed in all the fractions under study at 10 minutes indicating possibility of interaction with intact arecoline. Further, pretreatment of sulfhydryl reaction reagents decreased the specific activity of protein in mice injected with 3H arecoline.

The whole worm extract of Setaria cervi contains 52.7 mg Protein/g wet weight of the parasite.Fifty and 100% saturation of the extract with ammonium sulphate yielded two separate protein fractions. The antigen pattern in the parasite. was analyzed by various immunological tests such as gel diffusion, precipitin titration and passive cutaneous anaphylaxis (P. C. A.). Each rabbit was immunized by injecting a total of 3.7 mg protein according to the immunization schedule. Samples of sera collected on 32nd, 49th and 51st days were pooled in lot 1 and those collected on 55th, 57th and 59th days were pooled in lot II. Detection of antibodies by precipitin test showed that antibody titre reaches its peak in about 7 weeks and starts declining thereafter. The whole worm extract showed.4 precipitin bands with the immunized rabbit serum in gel diffusion. The two protein fractions obtained with 50 and 100% saturation with ammonium sulphate gave 3 and 2 bands respectively. Positive P. C. A. reaction was observed on guinea pigs with serum dilutions of 1 : 10 and 1 : 100. At a dilution of 1 : 1000 the reaction was negative. Positive reaction indicates the presence of reagin type of antibodies

Effect of oral administration of trimethoprim (TMP) in high doses on body wheight, blood biochemical parameter and hepatic functions were studied in albino rats. High doses of TMP caused anaemia and growth retardation of the experimental animals. Total lipid and cholesterol content of serum increased while protein and phospholipid content of serum was reduced following TMP. Administration of trimethoprim, in doses of 50 mg and 100 mg/kg/day for 3 weeks produced deleterious effect on liver as a result of which total lipid and cholesterol contents of liver and its microsomal fraction increased significantly with elevated aminotransferase activities, Protein, phospholipid and RNA contents of liver and liver microsomes were reduced in the drug treated animals, while alkaline phosphatase activity of serum and liver remained unchanged. Liverweight/body weight ratio of the treated animals was also decreased as compared to that of controls. Administratien of this drug in 50 mg and 100 mg/kg/day for 2 weeks showed the change of all that parameters and enzymes in a similar pattern but of lesser intensity. Alteration in the concentration of the above parameters and enzymes of serum and liver may be correlated to intracellular liver injury.

The effect of digoxin was studied, in graded concentrations of 2,8 and 32 'g/ml, on isolated straub's preparation of hypodynamic heart. Maximal positive inotropic activity was produced by 2 and 8 ug/ml of digoxin while the effect of 32 ug/ml was toxic.Potentiation of the positive inotropic activity of digoxin by physostigmine and inhibition by atropine, suggest that the action of digoxin is possibly mediated through the release of aceytlcholine. The positive intropic effect of digoxin was found to be decreased by pretreatment of heart with guanethidine, propranolol or phentolamine. These results are suggestive of probable release of catecholamines, potentiating the positive inotropic action of digitalis. Digoxin produced dose-dependent negative chronotropic effect, Pretreatment with physostigmine or atropine decreased the negative chronotropic action of digoxin. Guanethidine pretreatment with propranolol resulted in decreased negative chronotropic activity of digoxin. Digoxin was also found to produce occasional drop beats in concentration of 8-32 ug/ml. Physostigmine pretreatment slightly increased while atropine pretreatment slightly decreased the incidence of digoxin-induced drop beats. These results indicate that the conduction block in frog heart produced by digoxin was potentiated by cholinergic activity and inhibited by anti-cholinergic agents. Propranolol pretreatment was found to increase the incidence of drop beats in frog hearts. It is possible that in the frog heart, besides direct action of digoxin, there were adrenergic and cholinergic mediated actions. Blockade of adrenergic receptors produced a relative dominance of cholinergic activity potentiating the conduction block. In isolated frog heart, vagal stimulation-induced cardiac standstill or vagal stimulation-induced positive inotropic activity in atropine pretreated hearts, was not affected by digoxin treatment. These results suggest that in the existing experimental setup, the endorgan heart response to autonomic stimulation remained unaffected by digoxin treatment.

Three dosage levels of Monocrotophos, an organophosphorous pesticide, were selected for teratogenicity studies. Four groups of rats, each consisting of twenty pregnant rats, were dosed orally with 0.0 (control) 1. 2, 1.8 and 2.4 mg/kg/day from day 6 to I5 of pregnancy. In another series, same dose levels of the test drug were administered to four groups of rabbits each consisting of four pregnant rabbits, through 6th to 18th day of gestation. Monocrotophos had no dysmorphogenic effect on the fetuses in both the species. It could affect adversely by reducing fetal weight and mean litter weight of the pups at birth. Decrease in maternal whoie blood cholinesterase activity was noticed in a dose related manner. The weight of live pups at the time of weaning was also reduced significantly due to the pesticide with a concomitant decrease in the number of live fetuses. The reduction in the mean weight of fetuses and the new borns and the growth retardation at the time of weaning in the treated groups is an indication of embryotoxicity of the pestiade.

Intraperitoneally administered clonidine was found to prolong pentobarbitone sleeping time in mice. This effect of clonidine, though effectively antagonised by ip and icv administered chlorpheniramine, a H1 receptor blocker, and yohimbine,an (2 adrcnoceptor blocker, was not antagonised by ip and icv injected mctiamide, a H2 receptor blocker, and prazosin, an (1adrenoceptor blocker. Further, pretreatment with L-histidine, a precursor of brain histamine, and amodiaquine, an inhibitor of histamine N-methyl trausferase, in doses which had no significant per se effect on pentobarbitone-induced sleep, were found to significantly increase the effect of clonidine on pentobarbitone sleep. The results with chlorpheniramine, L-histidine and amodiaquine suggest an involvement of histamine in the potentiating effect of clonidine on pentobarbitone sleep. As the potentiation of pentobarbitone sleep by ip clonidine was antagonised by icv injected chlorpheniramine it suggests that activation of central H1 receptor mechanisms is responsible for the potentiating effect of clonidine on pentobarbitone sleep. Further, as icv injected yohimbine also antagonised the potentiating effect of ip clonidine on pentobarbitone sleep it suggests that the interaction of clonidine with the central histaminergic mechanisms is mediated through specific as adrenoceptors.

Blood levels of sulphadimidine (SDM) and Trimethoprim (TMP) combination have been studied in normal healthy volunteers. On the first day a single oral dose (SDM) 800 mg + TMP 160 mg) was given while on the second and third day the drug was administered twelve hourly. On an average the peak concentration of TMP in blood was obtained at 4th hour (2.66 'g/ml) and that of SDM by the 2nd hour (free 24.75 'g/ml, total 43.31 'g/ml). After multiple dosing on an average the increase in blood concentration at 48 and 72 hours was nearly 1.14 times for TMP and 1.53 and 1.51 times for free and total SDM respectively. The average blood ratio of SDM over TMP was maintained between 14 and 21 and indicates good distribution of SDM in the body.

Two calcium antagonists, viz., D-600 (a methoxy derivative of verapamil) and Nisoldipine, were tested for their influence on cardiac activity of frog heart in situ and rabbit atria. The interaction of these agents with the cardiotonic effects produced by the catecholamines, cardiac glycoside and free fatty acid (FFA), was also observed. Both the calcium antagonists exerted a negative cardiotropic effect on heart. They could affectively block the positive chronotropic effect, but not the inotropic effect of the catecholamines, both the positive chronotropic and inotropic effects of free fatty acids, but did not affect in any way the cardiotropic effect of digoxin.

Oleanolic acid 3-/3-Glucoside (RDG-1) was isolated from the seeds of the plant Randia dumetornm (Rubiaceae). The compound showed significant anti-inflammatory activity in the exudative and proliferative phases of inflammation in the doses of 25 and 100 mg/kg orally. Significant analgesia was observed only on thermal stimulus. It did not show any antipyretic activity against Brewer's yeast induced pyrexia in rats.The approximate oral LD50 were found to be 3600 mg/kg and 1500 mg/kg in mice and rats respectively.

Essential oil obtained from the grass Pseudosorghum (Family : Graminae) has been found to possess hypotensive, cardiac. depressant,, smooth muscle relaxant and mild tranquilhziog action.

A mixture of two chemically pure glycosides obtained from the stem bark of Symplocos spicata Roxb was studied for pharmacological actions. The glycosides (5 mg/kg, ip) possessed marked relaxant effect (equipotent with the relaxant effect of 10 'g/kg, iv adrenaline) on intestine in situ and transient hypotension in anaesthetised dog and moderate relaxant effect on isolated rabbit ileum. The spasmogenic responses of DMPP and acetyl-choline were attenuated by 40% and 55% respectively on isolated guinea-pig ileum. The glycosides had positive inotropic and chronotropic actions on perfused frog's heart and a weak curare-like activity on isolated frog's rectus abdominis muscle. The glycosides did not have any CNS activity.

: Pretreatmentwith morphine was found to decrease the intensity of methamphetaminc stereotypy in mice.This inhibitory effect of morphine on methamphetamine stereotypy was significantly increased by prior treatment with L-histidine, a precursor of brain histamine, in a dose which per se had no significant effect on methamphetamine stereotypy. Further, pretreatment with chlorcyclizine, a H1 receptor antagonist, not only increased the intensity of methamphetamine stereotypy but also prevented morphine from exerting an inhibitory effect on methamphetamine stereotypy.The results with L-histidine and chlorcyclizine suggest an involvement of central histaminergic mechanisms in the inhibitory effect of morphine on methamphetamine stereotypy in mice.

Dependence was induced in rats by repeated intraperitoneal injections of morphine sulfate withdrawal signs were precipitated by subcutaneous injection of naloxone. The dopamine agonists, i.e, apomorghine d-amphetamine and I-dopa aggravated the withdrawal signs while synthesis inhibitors / depletors of dopamine, i.e, reserpine and DL-a-methyl-p-tyrosine prevented the occurrence of almost all the withdrawal signs. These findings suggest the involvement of dopamine in the production of morphine dependence and withdrawal.

The effect of ranitidine was investigated on the contractile responses of frog rectus abdominis muscle to acetylcholine (Ach) and carbachol. Ranitidine was found to cause (a) potentiation of Ach responses but not that of carbachol, and (b) reversal of gallamine induced blockade of Ach contraction but not that of carbachol. Ranitidine was found to weakly inhibit the serum cholinesterases in-vim? The enzyme inhibition activity of ranitidine was very weak as compared to that of physostigmine.

The possible modulatory role of the central histaminergic system, in carrageenin induced pedal edema in rats, was investigated by central administration of histamine and histamine antagonists, and then noting their effects on the intensity and time course of the edema. Central administration of histamine significantly inhibited carrageenin-induced pedal inflammation throughout the period of observation. On the contrary, the H1 and H2 receptor antagonists, mepyramine and cimetidine respectively. enhanced the inflammatory response, though the results were statistically significant only with the former. The results have been discussed in the light of reported histaminergic influences on the hypothalamo-pituitary-adrenal axis and consequent increase in endogenous corticosteroid levels.

Department of Biophysics, Panjab University, Chandigarh Acid and alkaline phosphatase, citric acid and fructose level in epididymis, seminal vesicles and prostate were estimated in response to local irradiations of rat tests. The results show that these parameters are affected.

U-0882 unmasks hyperthermic response in the rabbit and hypothermic response in the guinea pig of endogenously released adrenergic mediator and potentiates corresponding response of injected noradrenaline and adrenaline by acting on central (-adrenoceptors. These receptors resemble the peripheral (-adrenoceptors in their susceptibility to U-0882.

Gangetin, one of the Pterocarpans, isolated from the hexane extract of the root of the plant Desmodium gangeticum.. The compound showed significant anti-inflammatory activity in the exudative and the proliferative phases of inflammation in the doses of 50 and 100 mg/kg orally. The compound showed significant analgesic activity. It did not show any anti-fertility and antipyretic activity in albino rats. It did not show acute toxicity in mice upto an oral dose of 7 g/kg.