Objective: To investigate the hepatoprotective activity of alcoholic (ALLT) and aqueous (AQLT) extracts of leaves of Tylophora indica (asclepiadaceae) against ethanol-induced hepatotoxicity. Materials and Methods: Leaf powder of Tylophora indica was successively extracted with alcohol and water. Preliminary phytochemical tests were done and the LD50 values for both extracts determined. The hepatoprotective activity of the ALLT and AQLT were assessed in ethanol-induced hepatotoxic rats. Results: The ALLT showed presence of alkaloids, carbohydrates, steroids, saponins and triterpenes, while alkaloids, carbohydrates and saponins were present with AQLT. The ALLT did not produce any mortality even at 5000 mg/kg while LD50 of AQLT was found to be 3162 mg/kg. Ethanol produced significant changes in physical (increased liver weight and volume), biochemical (increase in serum alanine transaminase, aspartate transaminase, alkaline phosphatase, direct bilirubin, total bilirubin, cholesterol, triglycerides and decrease in total protein and albumin level), histological (damage to hepatocytes) and functional (thiopentone-induced sleeping time) liver parameters. Pretreatment with ALLT or AQLT extract significantly prevented the physical, biochemical, histological and functional changes induced by ethanol in the liver. Conclusion: The present study indicates that ALLT and AQLT extracts possessed hepatoprotective activity. The alcoholic extract was found to exhibit greater hepatoprotective activity than the aqueous extract.

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Objectives: To study the effect of the crude aqueous extract from Viscum album (mistletoe) leaves on arterial blood pressure (BP) and heart rate (HR) in albino Wistar rats under pentobarbitone anesthesia. Materials and Methods: About 42 male rats (130-150 g) were randomly divided into three batches, as normotensives (NMT, n=18), renal artery-occluded hypertensives, (ROH, n=12), salt-induced hypertensives, (SIH, n=12), The normotensives were further divided into three groups, untreated (control), sham-operated and extract-treated subgroups (n=6 per subgroup) while the ROH and SIH groups were also divided into the treated and untreated subgroups of six rats each. The extract (150 mg/kg) was administered via the oral route, once daily for six weeks. Propranolol (0.5 mg/kg i.v.), atropine (1.5 mg/kg i.v.) and noradrenaline (1.0 mg/kg i.v.) were also administered to elucidate the probable mechanism of action of the extract. Results: The results showed that the control MAP and HR in the normotensives were 97.50±3.20 mmHg and 440.00±12.60 beats/min, respectively. The crude extract produced a significant decrease in BP i.e., 11.28, 23.98 and 18.80% in the NMT, ROH and SIH treated subgroups. The depression produced by the extract on the corresponding HR was not significant in the normotensive, ROH or SIH subgroups. Propranolol blocked the action of the extract on BP. However, atropine did not prevent the extract-induced depression of BP. The extract blocked noradrenaline-induced increase in BP in the NMT. Conclusion: Our data suggest that the mistletoe extract produces antihypertensive effect without alteration in HR, possibly involving sympathetic mechanism.

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Objective: To compare the efficacy, safety and tolerability of Boswellia serrata extract (BSE) in osteoarthritis (OA) knee with valdecoxib, a selective COX-2 inhibitor. Materials and Methods: In a randomized, prospective, open-label, comparative study the efficacy, safety and tolerability of BSE was compared with valdecoxib in 66 patients of OA of knee for six months. The patients were assessed by WOMAC scale at baseline and thereafter at monthly interval till 1 month after drug discontinuation. Antero-posterior radiographs of affected knee joint were taken at baseline and after 6 months. Results: In BSE group the pain, stiffness, difficulty in performing daily activities showed statistically significant improvement with two months of therapy which even lasted till one month after stopping the intervention. In valdecoxib group the statistically significant improvement in all parameters was reported after one month of therapy but the effect persisted only as long as drug therapy continued. Three patients from BSE group and two from valdecoxib group complained of acidity. One patient from BSE group complained of diarrhea and abdominal cramps. Conclusion: BSE showed a slower onset of action but the effect persisted even after stopping therapy while the action of valdecoxib became evident faster but waned rapidly after stopping the treatment.

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Objective: To detect potential adverse effects of aqueous extract of Labisia pumila var. alata (LPE) or `Kacip Fatimah' on the estrous cycle, reproductive performance, post-natal growth and offspring survival of rats. Materials and Methods: Forty eight (48) female Sprague Dawley rats with consecutive 4 to 6 days estrous cycle were given distilled water (as control) or LPE at 2, 20, 200, 400 or 800 mg/kg daily by gavaging ten days prior to mating, mating (a maximum period of ten days), gestation and lactation periods of seven days. Dams and fetuses were sacrificed on day seven postnatal. Results: Labisia pumila extracts did not alter the estrous cycle and general health of all rats. All the animals proceed towards successful mating and pregnancies. There was no significant difference in the duration of pregnancy and all pregnant rats delivered normally. Statistically no test agent-related changes in the maternal body weight, number of implantations, litter size and pup body weights were observed. Other parameters measured include pup sex ratio, live birth index, pup viability index and percentage of implantation death which also showed no significant difference. Conclusion: The present findings indicate that water based extracts of Labisia pumila var. alata do not pose any significant reproductive toxicity or complication in pregnancy and delivery in rats. The extract did not significantly alter the duration of pregnancy in rats, however the duration of delivery was not evaluated in this study.

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Objective: To study the antioxidant activity of various extracts and fractions of Acacia arabica by in vitro and in vivo experimental models. Materials and Methods: Various solvent extracts were prepared by Soxhlet extraction. Extract fractionations were done by solvent-solvent extraction and flash chromatographic separation. In vitro lipid peroxidation was carried out by tertiary butyl hydroperoxide -induced lipid peroxidation. The most active fractions were identified and standardized by thin layer chromatography (TLC). In vivo experiments on the most active fraction were carried out with 50, 100, and 150 mg/kg, p.o. doses, in carbon tetrachloride (CCl ₄ )-induced hepatotoxicity, in rats. Various biochemical parameters like serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), glutathione (GSH), and lipid peroxidation were estimated. Results: Flash chromatographic fractions 2-6 of ethyl acetate extract exhibited maximum activity with in vitro lipid peroxidation. In vivo evaluation of this active fraction (AA) in CCl4-induced hepatotoxicity for 19 days at a dose of 150 mg/kg offered marked liver protection, which was evident by significant changes in lipid peroxidation, glutathione, superoxide dismutase and catalase ( P <0.01). The treatment also showed significant changes in AST, ALT, and GSH-Px levels ( P <0.05). At lower doses, the protection was not consistent. Conclusion: The polyphenol rich active fraction of Acacia arabica is a potent free radical scavenger and hepatoprotective and protects TBH-induced lipid peroxidation and CCl ₄ -induced hepatic damage.

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Objective: To explore the effect of melatonin on the behavioral and biochemical parameters in sleep-disturbed mice. Materials and Methods: Male Laca mice (n=6-9/Group) were sleep deprived for 48-hours using grid suspended over water method. Melatonin was administered orally for 5 days (three day before 48-hours sleep deprivation. All the biochemical tests were performed in brain homogenates on fifth day immediately after behavioral observations. Results: Sleep deprivation caused rapid loss of body weight, reduction in locomotor activity, and severe anxiety in animals. Biochemically, sleep deprivation increased lipid peroxidation, nitrite and deplete reduced glutathione and catalase activities in the brains of mice which was significantly as compared to naοve animals (without sleep deprivation). Pre-treatment with melatonin (5 and 10 mg/kg) significantly improved body weight, locomotor activity, and anxiety in animals as compared to control (48-hours sleep-deprived mice). In addition, melatonin also significantly decreased lipid peroxidation, nitrite levels and reversed the depleted catalase and glutathione activity. Conclusion: Melatonin has protective action against sleep deprivation-induced behavioral and biochemical alterations.

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Objective: The objective of this study was to induce reproducible renal hypertension in rats using plexiglass clips, and to compare it with that induced by silver clips. Materials and Methods: Saw blades (0.21-0.22 mm thick ) were used to make clips (4 x 2 x 2 mm) from a piece of 2-mm thick plexiglass. Rats were subjected to sham-operation or placement of plexiglass or silver clips around left renal artery, and 4 weeks later their mean blood pressure (MBP, mmHg), heart rate (HR, bpm), and heart weight (HW), left kidney weight (LKW), right kidney weight (RKW) and body weight (BW, g) were determined. The RKW, LKW and HW were calculated as a percentage of body weight. Results: Four weeks after sham-operation or placement of clips around renal artery, MBP, HW and RKW were significantly higher and LKW was significantly lower in left renal artery-clipped rats using plexiglass or silver clips than sham-operated ones. There was also no significant differnce among the values of HR or BW from the 3 groups. Moreover, there was no significant difference among MBP, HR, LKW, RKW or BW from sham-operated or renal artery-clipped rats. Conclusion: The findings suggest that placement of solid plexiglass clips around left renal artery resulted in hypertension comparable to that induced by silver clips.

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Objective: To investigate recovery percentage of clenbuterol, nandrolone, stanozolol, and epimetendiol by two different solid phase extraction procedures viz. XAD2 (polystyrene divinylbenzene) and SPE columns (C18, Samprep, Rankem) so as to improve detection limit of anabolic steroids. Materials and Methods: The urine samples were spiked with different concentrations of drugs. The preliminary work was done with six samples, each of clenbuterol, nandrolone, and epimetendiol at 1, 2, 5, and 10 ng/mL and of stanozolol at 5,10, 20, and 40 ng/mL that were processed and injected into high resolution mass spectrometer. Later the study was limited to clenbuterol and epimetendiol at 2, 5, and 10 ng/mL concentrations. The data were analysed by comparing XAD2 and SPE column values. Results: The results show that the recovery percentage of nandrolone and stanozolol at various concentrations did not signify any difference between the two columns. However, there was a significant increase in the recovery of clenbuterol at 2 ng/mL ( P <0.002), 5 ng/mL ( P <0.001), and 10 ng/mL ( P <0.001) concentrations, where as for epimetendiol there was significant increase in the recovery at 2, 5, and 10 ng/mL ( P <0.01) with SPE column compared to XAD2 column. Conclusion: It is possible to enhance the detection limit of clenbuterol and epimetendiol by SPE column compared to XAD2 column. This procedure may be used for confirmation of suspicious samples found in routine testing.

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Monoclonal antibodies (MAbs), a new class of biological agents, are used these days in therapeutics and diagnosis. MAbs also labeled as 'magic bullets', are highly specific antibodies produced by a clone of single hybrid cells formed in the laboratory by fusion of B cell with the tumor cell. The hybridoma formed yields higher amount of MAbs. MAbs can be produced in vitro and in vivo . Animals are utilized to produce MAbs, but these antibodies are associated with immunogenic and ethical problems. Of late, recombinant DNA technology, genetic engineering,phage display and transgenic animals are used to produce humanized MAbs or pure human MAbs, which have fewer adverse effects. MAbs alone or conjugated with drugs, toxins, or radioactive atoms are used for treatment of cancer, autoimmune disorders, graft rejections, infectious diseases, asthma, and various cardiovascular disorders. New MAbs are being developed which are more specific and less toxic.

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Objective: To investigate the pharmacodynamic interaction of H2-receptor antagonists (i.e., famotidine and roxatidine acetate) with a neuromuscular blocker, pipecuronium using sciatic nerve stimulated gastrocnemius preparation of rats in vivo . Materials and Methods: The dose-response curve of pipecuronium (10-50 mg/kg i.v.) was elicited and the dose (ID50; 26.89 mg/kg i.v.) required to cause 50% of blockade of basal contractile twitch response was calculated. Benzyl alcohol (0.9 % v/v), famotidine (0.5, 2.0, 5.0 mg/kg i.v.) or roxatidine acetate (0.05, 0.2, 0.5 mg/kg i.v.) were administered 30 min prior to pipecuronium administration and their effects were studied on the dose-response curve of pipecuronium. Results: Famotidine did not alter the basal contractile twitch responses but with a dose of 2 mg/kg it significantly decreased, while with 5 mg/kg, it significantly increased the ID50 of pipecuronium. At higher dose (5.0 mg/kg) it significantly increased the time required for the onset of blockade without affecting the other parameters. Roxatidine acetate (0.2, 0.5 mg/kg) by itself produced significant neuromuscular blockade but did not alter the ID50 of pipecuronium, while with higher dose (0.5 mg/kg) it significantly decreased the same. Roxatidine (0.05 and 0.2 mg/kg) significantly increased the time required for onset of pipecuronium-induced neuromuscular blockade. At varying doses roxatidine also significantly increased the time required for peak effect and the recovery from the paralysis. Conclusion: Compared to roxatidine, famotidine produced less pharmacodynamic drug interaction with pipecuronium in rats. Such an interaction should be explored in clinical practice.

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