Objectives: Sub-acute toxicity study of a polyherbal drug (Prostlna) was carried out in albino rats to assess its effects on morphological, gross behaviour, body weight changes as well as to find out histopathological, biochemical and hematological changes. Methods: Eighty albino rats were divided equally into four groups.They were fed with distilled water, and the test drug (90, 300 and 450 mg/kg) daily for 90 days. Cage-side observation, changes in morphology, behaviour and body weight were weekly noted. At the end of the exposure period biochemical, hematological and pathological changes (macroscopic and microscopic) were examined. Results: The sub-acute toxicity studies on the drug reflected innocuous nature of this pdyherbal preparation on hepatic, renal and haemopoietlc system even on 15 times higher than recommended dose level (450 mg/kg body weight) on daily administration for 90 days. This is also confirmed by detailed histopathological studies. There was no change in rectal temperature and no mortality was seen. Conclusions: The polyherbal drug (Prostina) is devoid of toxic effects in rats upto the dose of 450 mg/kg which is 15 times higher than the recommended dose.

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Objective: To see the effect of Trikatu (piperine) on the bioavailability and pharmacokinetics of isoniazid in rabbits. Methods: In a crossover study, ten rabbits were administered either single dose (orally) of isoniazid (14 mg/kg) alone or in combination with Trikatu [piperine (10mg/kg)] Blood samples were collected at 0,0.5,1 ,1.5,2, 4,6,9 and 12 hours after drug administration and assayed for isoniazid by fluorimetric technique. A washout period of 7 days was allowed between the two treatments. Results : Coadministratfon of Trikatu (piperine) significantly reduced the Cmax (5.48 ñ 0.75 'g/ml vs 8.42 ñ 0.85 'g/ml; P < 0.05] and AUCo-( [15.04 ñ 3.64 'g/ml. hr vs 24.76(4.03 'g/ml. hr; P< 0.05] of isoniazid. Condusion: Trikatu (piperine) reduces the bioavailability of isoniazid in rabbits.

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Arsenic, a metalloid of highly toxic nature is present throughout the earth's crust. In India about 40 lakhs of people in West Bengal suffer from arsenic poisoning due to drinking water contamination. British Anti lewisite (BAL) is used for the treatment of arsenic poisoning. However, the chelator has low safety ratio and unpleasant side effects. Recently, few analogues of BAL, viz., meso 2,3-dimercaptosuccinic acid (DMSA) and sodium 2,3-dimercaptopropane 1 sulfonate (DMPS) beside few diesters and monoesters of DMSA have been successfully tried both in humans as well as in experimental models of acute and chronic arsenic poisoning. This article presents in briefly the recent development made in this area with possible directions for future research.

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Objectives: To assess the protective effect of Liv.100 against antitubercular drugs (isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA)) induced hepatotoxicity in rats. Methods:The simultaneous treatment of Liv.100 (400 mg/kg body weight) on antitubercular drugs (INH, RMP and PZA) induced lipid peroxidation in liver was studied in rats. Levels of marker enzymes such as lactate dehydrogenase, aspartate amino transferase, alanine amino transferase and alkaline phosphatase were assessed in liver and serum. The glutathione content and the activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S- transferase were estimated in liver. The levels of lipid peroxides and the activities of Na +K+ ATPase, Ca2+ ATPase and Mg2+ ATPase were also assayed in the liver of experimental groups. Results: In antitubercular drugs administered rats, a significant decrease was observed in the levels of marker enzymes in the liver with a corresponding increase in their levels in serum. The levels of lipid peroxidase (in terms of YBA reactants") were increased significantly in their serum and liver. The activities of Na+K+ ATPase, Ca2+ ATPase and Mg2+ ATPase were decreased significantly in their liver. The glutathione content and the activities of antioxidant enzymes decreased significantly in the liver of antitubercular drugs administered rats when compared to normal control. Simultaneous administration of Liv. 100, showed near normal levels of marker enzymes, and the levels of lipid peroxides glutathione content on comparison with normal control. Conclusion: Simultaneous treatment with Liv. 100 offers protection against hepatotoxicity induced by antitubercular drugs by reducing lipid peroxidation and restoring the antioxidant defense system.

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Objective: To evolve simple methods for the assay of ofloxacin in biological fluids. Methods: Simple methods for the estimation of ofloxacin in plasma, saliva and urine employing micro-biological assay using plate diffusion technique and by fluorimetric method based on the measurement of native fluorescence emitted by ofloxacin, have been described. Results: The recovery of ofloxacin from all the three biologial fluids was 93-98% and the sensitivity was 0.5 'g/ml on all 5 different occasions by both the methods. Anti-TB drugs viz., rifampicin, ethambutol, isoniazid and pyrazinamide and also anti-leprosy drugs viz., dapsone and clofazimine at concentrations of 10 and 20 'g/ml did not interfere with the estimation of ofloxacin by either method. Ofloxacin is stable in biological fluids for a period of at least 8 days at -20ø C. Conclusion: Both the methods described are simple, involve very few steps and do not need either costly chemicals or sophisticated equipments.

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Objective: To evaluate the various neuro-excitatory components of diazepam (DZP) withdrawal reactions and to correlate them with the brain levels of Gamma-Aminobutyrlc Acid(GABA). Methods: Diazepam withdrawal reactions were produced in rats by abrupt cessation of continued ascending doses of DZP viz 10,12,14,16,18 mg/ kg, twice a day, given for 5 days. Neuro-excitatory features were indicated by a fall in sleeping time and pain threshold and a rise in halothane need and behavioural index. The test groups received normal saline, clonidine 62.5 'g/kg or propranolol 10 mg/kg. Groups with continued DZP administration with or without abrupt cessation served as references for comparison. Brain GABA levels were estimated to establish correlation (if any) with the aforesaid experimental observations. Results: Abrupt DZP cessation after continued use evoked neuro-excitation and produced rise in behavioural index, halothane need and a fall in sleeping time, and in GABA levels in hypothalamus, corpusstrlatum and cerebellum. These changes were reversed by clonidlne or propranofol pretreatment. Conclusion: The study reveals that sudden stoppage of continued use of DZP produces withdrawal reactions. Fall in brain GABA levels confirms neuro-excitation. Clonidlne and propranold, inhibitors of central adrenergic outflow, reverse these changes.

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0bjective:To demonstrate that the inhibition of steroid 5(-reductase inhibitor could be conveniently and rapidly determined with common ultraviolet spectrophotometer. Methods: A biochemical method to determine the activity of steroid 5(-reductase was used to evaluate the inhibition of epristeride and ffnasteride to the enzyme. The OD value of each sample was measured continuously with ultraviolet spectrophotometer. for the reason that the substrate (NADPH) has a specific absorbent wave at 340 nm. The descending curve of OD value in each tube was described from the beginning to the tenth minute, by which the descending rate of each curve could be obtained through linear regression. The initial reaction rate, the slope of descending curve, resulted from difference between initial rate of each concentration and 0 concentration (blank control) of testosterone. It implicated the activity of the 5(-reductase. In order to prove this method feasible and the inhibition of the inhibitors reliable, an in vivo test was carried out. Twenty old-aged male mongrel dogs, with over 18 cm3 volume prostates though ultrasonic examination, were chosen in vivo experiment. Results: The inhibition constant of epristerlde (K,=25.1(1.2 nM) could be obtained according to the Lineweaver-Burk plots. Epristeride decreased the DHT concentration of serum and prostates. Conclusion: This method is convenient, rapid and effective for studying enzymatic kinetics of steroid 5(-reductase inhibitors

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Objective: To evaluate and compare the biorelease of fluticasone, a topically active synthetic corticosteroid alone with placebo (ointment base) and its combination with antifungal (miconazole. clotrimazole) and/or antibacterial agent (neomycin) based on attenuation of histamine induced wheal and flare reaction, and their intensity. Methods: The study was a randomized, open controlled and comparative trial, carried out in 24 healthy adult volunteers. Effect of different formulations on wheal and flare was observed after injecting histamine intradermally Results: Fluticasone alone and in different formulations were equally effective in reducing histamine induced wheal and flare, while their ointment bases did not alter the histamine response. Conclusion: Antibacterial (neomycin) and/or antifungal (miconazole, clotrimazole) agents did not alter the biorelease of fluticasone.

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0bjectives:To find the effect of pethidine on spermatogenesis in albino rats. Methods: Pethidine at the dose level of 5.0mg and 7.5 mg/kg. body wt in 0.2 ml saline was administered intraperitoneally to male albino rats for 30 days, suitable saline treated control group was maintained. Gonadosomatic index, spermatogenic elements, cauda epididymal sperm count, accessory sex organ weights were considered to study the effect of pethidine. Results: Pethidine administred at the dose level of 5.0 and 7.5mg/kg body wt has decreased the testis weight significantly (1101.51 ñ 56.76 mg/100 gm and 956.28 ñ 36.24 mg/1 00 gm ) when compared to the saline treated controls (1237.19 ñ 48.68 mg/100 gm). Simillarly the diameter of testis and seminiferous tubules is also reduced in pethidine treated albino rats (3.21 ñ 0.16 mm, 3.05 ñ 0.21 mm and 156.40 ñ 9.4 pm, 138.24 ñ 11.7 'm respectively from 3.72 ñ 0.12mm and 192.78 ñ 10.4'm) while the total cholesterol content of the testis increased (8.16 ñ 1.26 mg/gm and 10.21 ñ 2.05 mg/gm from 5.40 ñ 0.69 mg/gm). Pethidine has inhibited the process of spermatogenesis and reduced the caudaepididymal sperm count, accessory sex organ weights, and the protein and glycogen contents of the testis. Conclusion:Pethidine showed a dose dependent Inhibition on the gravimetrfc, micrometric and spermatogenic indices.

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Objective: To study the antinociceptive effect of the aqueous extract of Ziziphus spina christi (Linn) leaves. Methods: The antinociceptive effect of aqueous extract of Zizipus spina christi was studied using writhing test in rats. The animals were injected with the acetic acid and the number of writhings were counted in the control and experimental groups. Results: The extract (250 - 1000 mg kg-1) in a dose-dependent fashion significantly (P < 0.0005) reduced the number of wriths induced by 0.6% aqueous solution of acetic acid in Wistar rats.At a dose of 250 mg kg-1, the extract produced comparable effect to that of 10 mg kg-1 of pethidine hydrochloride in suppressing the number of wriths induced by acetic acid. Conclusion: Aqueous leaf extract of Ziziphus spina christi may possess antinocieceptive properties in the rat.

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The inhibitory neurotransmitter, (-aminobutyric acid (GABA), activates a variety of receptors in all areas of the central nervous system (CNS). Until recently, two receptor subtypes were known: bicuculline-sensitive GABAA and baclofen-sensitive GABAB receptors. Several lines of evidence now indicate the existence of a third class of GABA receptors. These novel GABAC receptors appear to be relatively simple ligand-gated Cl-channels with a distinctive pharmacology, in that they are not blocked by bicuculline and not modulated by barbiturates, benzodiazepines or neuroactive steroids. They are found predominantly in retina, insensitive to drugs that modulate GABAA and GABAB receptors and are activated selectively by cis-4-aminocrotonic acid (CACA). Compared with GABAA receptors, GABAC receptors are activated at lower concentrations of GABA and are less liable to desensitization. In addition, their channels open for a longer time. The pharmacology of these novel subtypes of GABA receptors may yield important therapeutic agents.

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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.

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