Objectives: To entrap methotrexate (MTX) complexed with (-Cyclodextrin ?(CD) into niosomes, to characterise niosomes for different physicochemical properties and to investigate the potential of niosome entrapped MTX- (-cyclodextrin complex in tumour treatment. Methods: MTX- (CD complex was entrapped into niosomes by lipid layer hydration method. The entrapment efficiency of the complex within the niosomes was determined by separating the unentrapped drug using dialysis. The in vitro release studies of the drug from niosomes were conducted in phosphate buffered saline pH 7.4. The vesicle stability was assessed by storage at room temperature, 37ø C and under refrigeration (4ø C) for a period of one month. The niosome entrapped MTX ?(CD complex was administered subcutaneously to C57BL/6J mice bearing melanoma B16F1 tumour at 10 mg kg -1 dose. The volume doubling time and growth delay of the tumour were taken as parameters to assess the antitumour efficacy. Results: The niosomal entrapment efficiency was higher in the case of MTX - (CD complex (84%) than with the plain drug (67%). Comparison of the drug release profile revealed a relatively slow release pattern of the entrapped drug complex from the vesicles as compared to plain MTX encapsulated niosomes. Better stability on storage was also observed with the niosome entrapped complex. The complex entrapped niosomes produced an improved anticancer activity as evident by enhanced volume doubling time and growth delay. Conclusion: This study indicated that complexation of methotrexate with (CD could increase the entrapment of the drug in non ionic surfactant vesicles and could improve the anticancer activity. Additionally, the present approach could be a means to control the duration of drug action in situ in cases where the dissociation constants of cyclodextrin drug complexes can be tailored.

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Objectives: To study the effects of 5-HT3 receptor antagonist ondansetron on learning and memory in rats. Methods: Wistar rats were treated with ondansetron in doses of 0.1, 1 and 10 mg/kg, intraperitoneally ( i.p.) and were subjected to the following tests: (1) passive avoidance test (PAT), (2) conditioned avoidance response (CAR) and (3) hole-board test. The latency to enter (LTE) in acquisition (AT) and retention trials (RT) was observed. Results: Ondansetron treated rats showed a significant improvement in the retention trials of PAT and CAR. There was also an increase in the exploratory behaviour of the ondansetron treated rats. Conclusion: Ondansetron produced a significant improvement in learning and memory in rats.

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Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are long-chain, polyunsaturated fatty acids of the n-3 series (n-3 PUFAs) obtained primarily from marine fish oils. They are reported to possess numerous health benefits. Taken orally, they are absorbed through lymphatic pathways, circulate largely in serum lipoproteins and distribute fairly widely in tissues. They are incorporated into cellular membrane lipids and compete with arachidonic acid in eicosanoid metabolism pathways. The biotransformation products may themselves be pharmacologically active. Reduced serum triglyceride level is the most consistent hypolipidemic action of EPA and DHA. They may reduce the severity of angina and prevent ischemia-induced ventricular fibrillation and sudden cardiac death. Although unable to arrest restenosis following coronary balloon angioplasty, animal experiments do indicate an antiatherogenic role. An antithrombotic effect, attributed to altered platelet function and possible modulation of the fibrinolytic system, and modest antihypertensive action, are also possible. Antiproliferative and cytotoxic influences have been noted on various cell lines and inhibition of mammary tumorigenesis has been documented in animal studies. Various anti-inflammatory effects have also been reported, such as in psoriasis and ulcerative colitis. However, the non-cardiovascular indications require further clinical exploration. Desirable changes occur at a threshold dose of around 2 g/day of n-3 PUFAs. Higher doses may have more pronounced effects but with the potential risks of upsetting the oxidant-antioxidant balance in the body and producing a higher incidence of nausea, eructation and diarrhoea. Other reported adverse reactions are uncommon. Fish oil preparations are generally well tolerated. Overall, EPA and DHA are desirable dietary supplements for maintaining cardiovascular health, notably in ischemic heart disease, and show promise in some non-cardiovascular disorders too.

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Objective: To evaluate the in-vivo performance of orally and transdermally delivered diltiazem hydrochloride in rabbits. Methods: Transdermal patches of diltiazem hydrochloride (DLT) were formulated employing ethyl cellulose and polyvinylpyrrolidone as film formers. The pharmacodynamic and pharmacokinetic performance of diltiazem hydrochloride after transdermal administration was compared with that of oral administration. This study was carried out in a randomized cross over design in male New Zealand albino rabbits. Results: The pharmacokinetic parameters such as maximum serum concentration (C max ), time for peak serum concentration (t max ), mean residence time (MRT) and area under the curve (AUC0-() were significantly (p <0.01) different following transdermal administration compared to oral administration. The terminal elimination half life of transdermally delivered diltiazem was found to similar that of oral administration. A sustained therapeutic activity was observed over a study period of 24 hrs after transdermal administration compared to oral administration. The skin irritation studies indicated that there is no recognisable changes on skin surface after the removal of polymeric films. Conclusions: The relative bioavailability of diltiazem hydrochloride and its therapeutic activity were increased about five fold after transdermal administration compared to oral route.

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Objectives: a) To study the effect of S-allyl cysteine sulphoxide (SACS) on histological and ultrastructural changes in liver, kidney, heart and brain produced by monosodium glutamate (MSG) in rats on atherogenic diet. b) To understand some cellular effects of MSG at higher dose in renal and hepatic tissues of rats on atherogenic diet. Methods: Rats on atherogenic diet with MSG at two different doses received SACS for 30 days. At the end of 30 days, Na+ , K+ ATPase, 5' nucleotidase and membrane fluidisation assays were carried out in heart, kidney, liver and brain, respectively. Histological observation was also carried out for liver and kidney. Results: SACS significantly decreased the Na+, K+ -ATPase and 5' nucleotidase activities in liver, kidney and heart in rats treated with MSG at both doses. There was no significant effect of SACS on brain Na+ ,K+ -ATPase and 5' nucleotidase in rats treated with both doses. Further, SACS significantly increased membrane fluidisation pattern in liver, kidney and heart in rats treated with MSG at both doses. MSG at higher dose produced sequence of damage in cellular organelles and membranes in renal and hepatic tissues. There was no significant effect of SACS on architectural, ultrastructural and histological changes induced by MSG in rats on atherogenic diet. Conclusion: SACS significantly antagonised the reversible damage produced by MSG in rats onatherogenic diet by modulating Na+ , K+ -ATPase, 5' nucleotidase and membrane fluidisation process. Irreversible damage (oxidative stress) caused by MSG at higher dose on cell membrane and cell organelles of hepatic and renal tissues is not reverted by SACS in rats on atherogenic diet.

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Objectives: To assess the therapeutic efficiency of N-acetylcysteine (NAC) and Vitamin C (VC) by estimating the activities of tumour marker enzymes in vitro. Methods: Human lung carcinoma cell line, NCI-H82, was maintained in RPMI-1640 medium. The cells were divided into three groups (group II, III and IV) and each monolayer was subjected to drug treatment with NAC, VC and NAC+VC respectively. The cells without any supplementation served as control (group I). After 48 hours supplementation with the drugs, the cells were harvested for the estimation of aldolase, (-GT, 5'-nucleotidase, adenosine deaminase, lactate dehydrogenase and creatine kinase. Results: The activities of aldolase, (-GT, 5'-nucleotidase, lactate dehydrogenase and creatine kinase were found to be altered but no change could be observed in the activity of adenosine deaminase. Conclusion: The enzymes studied were found to be affected by the action of N-acetylcysteine and vitamin C, and this effect of the drugs on enzymes might contribute to the drugs action against cancer cells.

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Objective: To study the effects of phenobarbitone, carbamazepine and sodium valproate treatments on the elimination kinetics of acetaminophen in rabbits. Methods: In the control session, each rabbit was treated with an intravenous dose of acetaminophen (46.67 mg/kg, i.v.). Starting on the following day, rabbits in the three groups were treated with phenobarbitone (16.33 mg/kg/day; p.o.; 21 days), carbamazepine (56.00 mg/kg/day; p.o.; 10 days) and sodium valproate (65.00 mg/kg/day; p.o.; 7 days), respectively. Acetaminophen administration was repeated on the subsequent day. Blood samples were collected in each session, for the estimation of plasma acetaminophen levels. Result: In the phenobarbitone treated group, clearance rate of acetaminophen was increased. It was not significantly changed in the both carbamazepine and sodium valproate treated groups. Conclusion: Phenobarbitone induced the metabolism of acetaminophen in rabbits whereas carbamazepine and sodium valproate failed to do so.

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Objectives: To investigate the influence of tricyclic antidepressants (TCAs) viz., desipramine (DMI), clomipramine (CLO) and amitriptyline (AMI) on resutured incision and dead space wound healing. Methods: Resutured incision and dead space wounds were induced in Wistar rats of either sex under light ether anaesthesia, taking aseptic precautions. Control animals received normal saline and other groups received DMI, CLO and AMI for a period of 10 days. On eleventh day after estimating breaking strength of resutured incision wounds (under anaesthesia) animals were sacrificed and granulomas were removed for estimating breaking strength, quantification of granulation tissue and their biochemical as well as histological studies in control and various treated groups. Results: Both DMI and CLO significantly increased the breaking strength of incision wound, dry weight and hydroxyproline content of granulation tissue when compared to control group. In AMI treated group there was no significant change in both the wound models employed. Conclusion: DMI and CLO may promote wound healing while AMI did not affect the healing.

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Objective: To investigate whether the coadministration of isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA) was more potent than RMP alone in the induction of drug metabolizing enzymes and the causation of oxidative stress in the mouse. Methods: Male mice were administered intraperitoneally 40 mg RMP or simultaneously 40, 40 and 80 mg INH, RMP and PZA per Kg body weight for 3 days. The livers were homogenized in potassium phosphate buffer containing potassium chloride. Microsomes and 100,000 x g supernatant were prepared by differential centrifugation. Assays of cytochrome P450, NADPH cytochrome c reductase, erythromycin N-demethylase and lipid peroxidation were performed in the microsomes. Assays of glutathione reductase, glutathione peroxidase and catalase were performed in 100,000 x g supernatant. Glutathione was assayed in supernatant from 5% TCA homogenate of the liver specimen. Results: Coadministration of INH, RMP and PZA increased the hepatic microsomal cytochrome P450, lipid peroxidation, the activities of NADPH cytochrome c oxidoreductase, erythromycin N-demethylase, Se-independent glutathione peroxidase and intensified 53.5 and 56 kDa polypeptides in the mouse. RMP increased all these parameters except the activity of selenium independent glutathione peroxidase. However, changes caused in the lipid peroxidation and the activity of erythromycin N-demethylase by coadministration of INH, RMP and PZA were more dramatic as compared to RMP. Both treatments did not alter the hepatic glutathione and activities of glutathione reductase, Se-dependent glutathione peroxidase, superoxide dismutase but decreased the activity of catalase in the mouse. Conclusion: Coadministration of INH, RMP and PZA was more potent in the induction of the hepatic microsomal erythromycin N demethylase and causation of oxidative stress in the mouse as compared to RMP administration alone.

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Objective : To investigate the effect of lithium (Li) on some aspects of reproductive physiology, comprising of luteinizing hormone (LH) activity and changes in the maternal behaviour of albino rat. Methods : Oestrous cycle, receptivity of female rat on the days of oestrus and incidence of mating confirmed by presence of sperm in vaginal smear were studied. Rats with sperm positive vaginal smear were isolated and observed for pregnancy state. The maternal behaviour was assessed by behaviour profile of lactating mother. Simultaneous measurement of Li concentration in brain and serum and level of circulating luteinizing hormone (LH) were carried out to indicate the involvement of endocrine vis-a-vis neuronal correlates. Results : A significant delay in normal oestrus, reduced number of foetuses, difficult labour, maternal indifference to litters and cessation of nursing were associated with observation of reduced circulating LH level and with accumulation of Li in brain and serum. Conclusion : Changes in the reproductive behaviour associated with reduced levels of circulating LH were correlated with the presence of Li ion in brain and plasma.

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Objective: Studies have shown that expression and localisation of nitric oxide synthase (NOS) depends on the type and differentiation status of different types of tumours. The present study was conducted to evaluate the expression of NOS in carcinogen induced tumour. Method: Swiss albino mice were injected with 20-methyl cholanthrene. Seventy six percent of the animals were positive for fibrosarcoma at the end of 100 days following exposure. The tumours were excised when they reached a predetermined size and immunostained for inducible and neuronal NOS. The staining was graded on an increasing intensity scale. Results: The tumour sections stained very strongly for iNOS as compared to controls (identical sections from tumour negative mice). Weak staining was detected for nNOS in the tumour sections unlike controls. Conclusions: NO may be involved in carcinogen induced fibrosarcoma as seen from the expression of its synthesising enzymes.

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Objective: To study the neuropsychobehavioural effects of traditional silver preparations: Raupya Bhasma, Kushta Nuqra and Chandi Warq. Methods: The preparations were subjected to a battery of 30 tests for general neuropsychopharmacological effects, cognitive functions, antidepressant, anxiolytic, neuroleptic and serenic activities, effects on growth, body weight, endurance and fatigue. Results: The test drugs (50 mg/kg, p.o.) caused significant reduction of haloperidol-induced catalepsy in rats. Incorporation in the diet of rat pups (1% w/w for 6 weeks) lead to significantly higher growth rate when compared to control animals. No appreciable effects were discernible on other parameters. Conclusion: Silver preparations used in Ayurveda and Unani-Tibb showed anticataleptic and growth promoting effects without gross or subtle toxicities, weight loss, sedation, motor deficit, aggression or ill effects on cognitive functions.

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