The effect of Shilajit was investigated for putative nootropic and anxiolytic activity, and its effect on rat brain monoamines using Charles Foster strain albino rats. Nootropic activity was assessed by passive avoidance learning and active avoidance learning acquisition and retention. Anxiolytic activity was evaluated by the elevated plus-maze technique. Rat brain monoamines and monoamine metaboliteswere estimated by a HPLC technique. The results indicated that Shilajit had significant nootropic and anxiolytic activity. The biochemical studies indicated that acute treatment with Shilajit had insignificant effects on rat brain monoamine and monoamine metabolite levels. However, following subacute (5days) treatment, there was decrease in 5-hydroxytryptamine and 5-hydroxyindole acetic acid concentrations and an increase in the levels of dopamine, homovanillic acid and 3.4-dihydroxyphenyl-acetic acid concentrations, with insignificant effects on noradrenaline and 3-methoxy-4- hydroxyphenylethylene glycol levels. The observed neurochemical effects induced by Shilajit, indicating a decrease in rat brain 5-hydroxytryptamine turnover, associated with an increase in dopaminergic activity, helps to explain the observed nootropic and anxiolytic effects of the drug.

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If two beta adrenoceptor antagonists are to act together, the theory predicts that the combined blocking effect will be additive. This concept was subjected to experimental verification. Three models namely isolated, spontaneously beating guinea-pig atrium, isolated guinea-pig trachea and in vivo experiments using anaesthetized rats were used. Concentration/dose-response curves were established in all models. lsoprenaline as agonist and various beta receptor antagonists were used in the study. Dose ratio resulting from the shift of agonist curve was obtained for an individual antagonist. When two antagonists were added in combination, dose ratio for the combination was obtained. This experimentally derived dose ratio due to combination of antagonists was compared with the one expected on the theory. In isolated atrium model the dose ratio study revealed that in case of 2 pairs viz. (i) pindolol & labetalol and (ii) sotalol & labetalol the dose ratios with combination of antagonists were infra-additive. With other pairs additive effect was seen. With one pair supra-additive effect was noted. In case of tracheal tissue metoprolol & labetalol resulted into infra-additive effect and combination of labetalol & propranolol resulted into supra-additive effect. In In vivo experiments dose ratio study exhibited infra-additive effect with two pairs viz. (i) sotalol & labetalol and (ii) sotalol and metoprolol. Additive effect was seen with other two pairs. In rats treated with sotalol chronically dose ratios obtained with labetalol and metoprolol were very low indicating infra-additive effect. The results obtained in the study are not in accord with theory of competitive antagonism. Though it is difficult to explain these results, it is suggested that effects observed could arise if the beta blockers are considered to be metaffinoid rather than competitive antagonist. Thus the study provides evidence against considering beta blockers as pure competitive antagonists.

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The rate of dopamine or serotonin synthesis in rat brain striatal synaptosomes was determined as a function of pH. Optimal pH for serotonin synthesis was about 7.2 and as the pH of the suspension medium decreased below 7 the rate of serotonin formation declined. Optimal pH for dopamine production was at 6.1 and when experiments were performed at pH 7.4 the rate of dopamine formation decreased to about 25% of that at pH 6.1. Addition of either dopamine or serotonin to the suspension medium inhibited the rate of dopamine and serotonin formation by the synaptosomes. lt appears that dopamine and serotonin interaction plays an important role in the control of neural function during brain pH changes. It is concluded that synaptosomes may be used as a suitable model to study the neurochemical changes of the brain during acidosis.

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The relationship between plasma, saliva and urine ciprofloxacin concentration was investigated in 16 normal male healthy volunteers after oral administration of 750 mg. Peak plasma concentration of 4.8 mg/ I was achieved between 1 to 1.5 h after drug administration. The pharmacokinetics of ciprofloxacin in our population was not different from that reported in the literature. The salivary concentration of the drug was lower and it declined more rapidly than that in plasma. The agreement between estimations in the two biological fluids was poor. Between 15 - 38 % of the dose was recovered unchanged in urine till 12 h after drug administration. A good correlation (r =0.84; P c 0.005) was seen between creatinine clearance and renal clearance of the drug. The elimination half-life calculated using plasma , saliva and urinary levels were 6.2, 4.6 and 3.6 h respectively. It is concluded that neither saliva nor urine can be substituted for plasma sampling in pharmacokinetic studies of ciprofloxacin.

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To investigate the histamine receptor sub-types in the chicken oesophagus, the isotonic responsiveness of isolated oesophagus to histamine receptor agonists and antagonists was examined in vitro. Histamine and 2-pyridylethylamine (2-PEA) produced a concentration related contraction which was antagonized by mepyramine. Histamine did not produce relaxation of carbamylcholine contracted tissues although histamine-induced contraction was potentiated in the presence of cimetidine, phentolamine or propranolol. Dimaprit produced a concentration-dependant relaxation which was partly antagonized by cimetidine. Phentolamine and propranolol did not modify the dimaprit-induced relaxation. Longitudinal smooth muscles of chicken oesophagus seem to contain both H1 and H2 histamine receptors. The inhibitory H2 receptors appear to be usually masked by the overwhelming predominance of the excitatory H1receptors.

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A randomised clinical trial was done to assess the efficacy of Herborheumal, a new herbal compound, in post-operative surgical patients. It was found to be an effective anti-inflammatory and analgesic in comparison with placebo and ibuprofen.

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Pharmacokinetics and dosage regimen of gentamicin were investigated in rabbits following a single intramuscular administration of 4mg/kg. The absorption and elimination half lives and apparent volume of distribution were 4.8ñ 0.6 min,44.4ñ 9.0 min and 0.45 ñ 0.11 l/kg ,respectively. Therapeutic plasma levels of 1 ug/ml were maintained upto 2 h. A satisfactory intramuscular dosage regimen would be 3.48 mg/kg and 3.l0mg/kg as priming and maintenaance doses, respectively, to be repeated at 2 h intervals.

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