The herb Artemisia annua has been used for treatment of fever in China for more than thousand years. Artemisinin (qinghaosu), a sesquiterpene lactone is the active principle of Artemisia annua. Its peroxide configuration is responsible for its antimalarial activity. Artemisinin and its derivatives are very rapidly effective against malarial parasites including multidrug resistant strains of P.falciparum but recrudescences are commonly reported, suggesting that these drugs should not be used alone for the treatment of faiciparum malaria. Although administered to over one million people all over the world, no clinical resistance or serious adverse effects have been reported. In pregnancy artemisinin derivatives should not be used as primary drug for uncomplicated malaria but they can be used for severe infections in areas of multidrua resistance. They should be reserved for curative treatment " and not be used for prophylaxis.

Objectives: The present study is aimed at finding the effect of propolis (a natural resin produced by honey bees, rich in flavonoids) in a model of hepatotoxicity produced by alcohol and carbon tetrachloride (CCl4) in vivo. Methods: The effect of intraperitoneal (i.p.) administration of propolis (50 and 100 mg/kg) was studied on hepatotoxicity produced by alcohol (40%, 2.0 ml/100 gm, p.o for 21 days) and CCl4 1:1 in groundnut oil 0.1 ml/kg, S.C. on 20th day. Serum transaminases, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood and tissue glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) in liver were estimated following the established procedures to assess the liver function. Biochemical observations were supplemented with histological examination of liver sections. Results: ALT and AST which were elevated by alcohol and CCl4 (68.39 ñ 1.87 and 65.89 ñ 0.75 IU/L) were lowered to physiological levels (39.33 ñ 0.90 and 40.66 ñ 0.51 IU/L) by co-administration of propolis. Glutathione (GSH) that was reduced significantly in blood and liver (0.036 ñ 0.05 mg% and 7.34 ñ 0.043 'moles/gm tissue) was brought back to near normal level (0.925 ñ 0.04 mg% and 9.03 ñ 0.09 'moles/gm tissue). The lipid peroxides were increased (1.93 ñ 0.15 nmoles MDA/mg protein) in alcohol and CCl4 treated group. Propolis reduced the lipid peroxides level (1.02 ñ 0.03 nmoles MDA/mg protein) in liver. Multifocal necrotic changes of liver by CCl4 and alcohol treatment were minimised to near normal morphology by propolis. Conclusion: Propolis showed a dose dependent protective effect on alcohol and CCl4 induced hepatotoxicity. The effect was more pronounced in 100 mg/kg propolis treated rats and was comparable with a standard hepatoprotective preparation, Liv.52.

Objectives: Cleistanthus collinusa toxic plant, is frequently implicated in suicidal and homicidal poisoning. Its exact mode of toxicity is unravelled which is very essential to develop suitable strategy to antagonise toxicity. In congnisance with the prevailing situation of C.collinus the present study was undertaken to characterise the precise mode of action. Methods: C.collinus leaf extract (20% w/v) was administered at 24h LD50 dose orally to 18h starved rats (8g Kg-1) and rabbits (l0gKg-1) which sacrificed after 180 minutes and vital organs were assayed for glutathione and ATPase. Results: Glutathione profile revealed its depletion in various organs of rats (64.95% in liver, 51.60% in kidney, 15.60% in heart, 25.20% in brain and 27% in skeletal muscle) and in rabbits (42.60% in liver, 52.50% in kidney, 17.30% in heart, 13.50% in brain and 48.60% in skeletal muscle) as compared to that of the controls in the respective species. A similar trend of inhibition of ATPase activity was observed in the vital organs of rats (P<0.001, P<0.01) as well as in the case of rabbits (P<0.01). Conclusion: It can be deduced from the present profile that C.collinus during its assualt causes a definite depletion/inhibition of thiol/thiol containing enzymes which is responsible for the manifestation of toxicity and the present finding could pave way for the selection of thiol compounds as probable antidotes to combat C.collinus toxicosis.

Objectives: The present study was carried out in normal subjects (89 in number) and hypertensive patients (118 in number) to evaluate the effects of hypertension per se and the antihypertensive agents on haemostatic variables. Methods: Haemostatic variables like prothrombin time, partial thromboplastin time, thrombin clotting time, heparin thrombin clotting time, Factors VII and VIII, fibrinogen, platelet count, platelet aggregation, euglobulin clot lysis time and antithrombin Ill were estimated in normal subjects. freshly detected hypertensives and the patients already receiving treatment with various antihypertensive agents. The tests were repeated in the freshly detected cases after six months therapy. Results: Freshly detected hypertensive patients were found to have abnormalities in some of the haemostatic variables such as increased factor VIII (mean ñ SE; 116.71 ñ 3.69%), reduced PT (14.83 ñ 0.25 secs) and HTCT (24.50 ñ 0.93 secs) values. On the other hand in the patients already receiving treatment PTT-K values were reduced (36.76 ñ 1.16 secs) and factor VIII (118.12 ñ 2.22%) and fibrinogen levels (512.32 ñ 11.82 mg%) increased compared to normals. Fibrinolytic activity was also reduced in both the groups with values of ECLT being 196.91 ñ 10.66 and 197.20 ñ 7.27 mins. respectively and ATIII levels being 73.12 ñ 2.72% and 73.77 ñ 2.72% respectively compared to normals. While PAT with ADP was significantly increased (52.33 ñ 2.68%) in freshly detected patients, PAT with collagen was significantly reduced (40.51 ñ 1.96%) in patients already receiving treatment. Platelet counts were also high in these two groups with the values being 206.42 ñ 7.02 x l03 cumm and 195.45 ñ 2.91 x 10 3 cumm respectively. Conclusion: The study suggests that there could be an increased risk of thromboembolic complications in hypertensive patients. Therefore, there is a need to monitor the haemostatic variables in hypertensive patients in order to prevent thrombogenic complications.

Objectives: To investigate the relationship between the structure of dermorphins (DM) and their pharmacological properties, six analogues of [Hyp6] DM and [Pro6] DM were synthesised and their biological activities were studied. Methods: The peptides were synthesised by the solid phase method using 9-fluorenylmethoxycarbonyl amino acid trichlorophenyl esters as coupling agents and Merrifield resin as solid support. The opioid agonist activity was studied using co-axially, electrically stimulated contraction of isolated guinea pig ileum (GPI, in vitro). Their analgesic activity was assessed in mice using Eddy's hot plate method and tail-flick method. The antidiarrhoeal activity was determined by the charcoal meal test in mice. Results: In the GPI assay, the synthetic analogues possess agonistic activity that are less pronounced than morphine. Peptides I and II (substitution of ser at position 7 and Gly at position 4 in [Hyp6] DM series respectively) possessed considerable analgesic activity but are almost inactive in the GPI assay. Peptide Ill ( [ Pro6, Sar7] DM) possess only analgesic activity. In GPI assay, peptide IV was inactive. Peptide V and VI had equipotent analgesic and antidiarrhoeal activity. Conclusion: Peptides with various structures can possess specificities that may prove useful in biolo ical applications. Among them [Sar4, Hyp6, Tyr7] DM, [Hyp6. Pro7] DM, [Pro6, Sar ] DM and [Phg3,Pro4 ] DM exhibited a high degree of selectivity in their activities.

Objective: To determine antihypertensive effect of supplemental dietary calcium alone or in combination with diltiazem in eperimentally induced hypertensive rats. Methods: In the first set of experiment rats were fed with calcium enriched diet (CED 2%). BP and pressor response to NA and ADR were recorded. In the second set of experiment hypertensive rats (DOCA, CdCl2 or estrogen) treated with CED were recorded for BP and pressor response to NA and ADR. In the third set of experiment hypertensive rats treated with CED and diltiazem were recorded for BP and pressor response to NA and ADR. Results: Chronic administration of 2% CED (daily for 8 weeks) alone or in combination with diltiazem produced a significant reduction in BP of normal and hypertensive (DOCA, CdCl2, EO) rats. The pressor response to NA and ADR were significantly reduced in CdCl2 treated rats fed with 2% CED and there was a significant decrease in pressor response to NA and ADR in hypertensive rats treated with diltiazem and 2% CED. Conclusion: Supplemental dietary calcium may bring about stabilisation of ionic fluxes and decrease the abnormal intracellular calcium level implicated in hypertension while combination of CED with diltiazem produced additive antihypertensive effects.

Objectives: To study the effect of cell culture extract of Hemidesmus indicus (CCH) on normal and hypercholesterolemic rats for various lipid profile in serum, tissues and fecal matter. Methods: Twelve groups of eight animals were subgrouped into three set of experiments. First group received normal and CCH (2, 4 and 16 mg/kg, p.o.) for 30 days, second group received atherogenic diet for 30 (l-30) days and CCH (2, 4 and 16 mg/kg, p.o.) for next 30 (31-60) days, third group received atherogenic diet and CCH (2,4 and 16 mg/kg, p.o.) for 60 days concurrently. Serum tissue and faecal lipid profile were analysed. Results: It was observed that the CCH (2, 4, and 16 mg/kg, p.o.) had prevented hypercholesterolemia in rats. Rats which received atherogenic diet for first 30 (l-30) days when subjected to CCH (2, 4 and 16 mg/kg, p.o.) for next 30 (31-60) days showed significant treatment reduction (p<0.01) of lipid levels in serum. When atherogenic diet and CCH were given together for 60 (l-60) days there was significant (p<0.01) reduction of lipid in liver, heart and serum fecal excretion of cholesterol and phospholipids were significantly increased (p<0.01 in rats fed with CCH. Conclusion: Atherogenic diet along with CCH concurrently lowered the levels of serum, tissue and fecal lipid levels.

Objectives: To study the effects of different parts of Sida rhombifolia on chemical and drug induced hepatotoxicants and on carrageenan induced paw oedema in rats. Methods: Hepatotoxicity was induced in rats by treatment with carbon tetrachloride, paracetamol and rifampicin and the hepatoprotective activity was measured by determining various enzymes and bilirubin levels in serum. Oedema was induced by carrageenan and the oedema suppressant activity was measured using a plethysmometer. Results: The powdered roots aerial parts and their aqueous extract showed significant hepatoprotective activity. The methanolic extract of the aerial parts showed significant oedema suppressant activity in rats. Conclusion: The hepatoprotective activity of the powdered drug and its extract may be due the stimulatory effects on hepatic regeneration or free radical scavenging effects, etc. The oedema suppressant activity the drug may be due to the inhibitory effects on the release of histamine like substances.

Objectives: Aspirin has been shown to produce defect in neural tube development in chick embryo and this effect could be antagnozied by pre-treatment with PGF2(. Diflunisal inhibits prostaglandin synthesis and is likely to be used during pregnancy. Hence, the present work was undertaken to find out whether like aspirin, diflunisal also affects neural tube development in chick embryo. Methods: (i) Diflunisal in four doses, viz. 3. 6, 30 and 60'g/embryo was injected sub-blastodermally by window technique in fresh embryonated eggs after 17 hours of incubation at 39(0.5(C. Eggs were re-incubated and harvested at 40 hours (ii) Effect of PGEI (5'g) and PGF2(, (5'g) was studied on the defect induced by diflunisal (6'g) (iii) Effect of diflunisal (6'g) and aspirin (30'g) was studied at different time intervals uptil neural tube formation i.e., drugs were injected at 17 hours and embryos were harvested at 22 hours, 27 hours and 40 hours. Results: All the four doses of diflunisal produced significant changes in neural tube development of chick embryo. PGE1 and PGF2( treatment potentiated the effect of diflunisal. Aspirin induced neural tube defect was seen at 22 hours and remained same till 40 hours, whereas it was observed that effect of diflunisal was delayed it could be observed at 40 hours. Conclusion: Diflunisal, produces neural tube defect in chick embryo but this action is not mediated by prostaglandins. may be it acts at some other cellular level which requires some time for its action.

Objectives: To analyse the functional significance of Nitric oxide (NO) in cardiovascular regulation from rostral ventral medulla in cats using nitric oxide precursor, donor and guanylate cyclase inhibitor, methylene blue. Methods: Arterial pressure was recorded from femoral artery of chloralose anaesthetized cats through statham P23 DC transducer on Grass model P7 polygraph and the heart rate was also triggered using Grass 7P4 tac hograph. The effect on blood pressure and heart rate was monitored following topical application of NO precursor, L-Arg (1,2 and 5% for 10 minutes), NO donor, sodium nitroprusside (SNP) (0.1 and 0.5% for 10 minutes) and methylene blue (MB) (1% for 10 minutes) on exposed rostro-ventral medulla. Results: L-Arginine (1,2 and 5%) did not produce significant effects on blood pressure and heart rate. However, topical application of SNP ( O.1%-0.5%) produced significant hypotension and bradycardia which was attenuated by guanylate cyclase inhibitor methylene blue. Conclusion:The significant hypotension and bradycardia produced by SNP and blockade by methylene blue suggests the possible involvement of NO-cGMP mechanism in central cardiovascular regulation.

Objectives: To evaluate the in vitro effect of sobatum on UV light induced damage and the production of superoxides by the photoactivation of riboflavin. Methods: The inhibitory effect of sobatum on UV light induced free radicals was determined using the bacteria Salmonella typhimurium. In this assay different concentrations of the sobatum in O.1ml DMSO were incorporated into the nutrient agar plates and the bacteria (1O8 cells in 0.1 ml) were spread on all the petri dishes using a sterile loop and all the petridishes were irradiated. At the end of 24 hours, the number of colonies in each plate were counted and the increase in number of colonies in the sobatum incorporated petridishes were compared to the control petridish. Effect of sobatum on superoxide production was determined by its ability to inhibit the reduction of nitro blue tetrazolium (NBT) by superoxides generated by the reaction of photo reduced riboflavin and oxygen. Results: Sobatum significantly inhibited UV induced damage in Salmonella typhimurium. The inhibitory effect of sobatum on superoxide production by the photoactivation of riboflavin was about 79.40% (0.4mg sobatum) when compared with control. Conclusion: Sobatum inhibits the UV light induced damage due to its free radical scavenging property.

Objectives: To study the anti-inflammatory effect of nifedipine, verapamil and diltiazem on carrageenin-induced hind paw oedema and granuloma pouch in rats. Methods: Hind paw oedema was produced by subplantar injection of 0.1 ml of freshly prepared 1% suspension of carrageenin in normal saline and paw volume was measured plethysmometrically at 0 hour and 3 hours after carrageenin injection. Granuloma pouch was produced by the injection of 4 ml of 2% (w/v) carrageenin in sterile normal saline in the nape of the neck. The animals were sacrificed on the sixth day and the volume of pouch fluid and wet weight of granulation tissue were measured. Results: Nifedipine, verapamil and diltiazem produced significant and dose-dependent anti-inflammatory effect in rat hind paw oedema and were found to be more potent as compared to aspirin. Nifedipine produced significant inhibition of the volume of the pouch fluid and weight of the granulation tissue in granuloma pouch. Verapamil and diltiazem produced no significant effect. Conclusion: Nifedipine has anti-inflammatory effect both in acute and chronic inflammation, Verapamil and diltiazem possess anti-inflammatory effect only in acute inflammation,

Objectives: To compare the pharmacokinetics of two brands of oral cyclosporin solution was compared in healthy male volunteers. Methods: A single oral dose of 15mg/kg of either test or reference preparations of cyclosporin was administered to all the volunteers in double blind randomised cross over fashion. Plasma levels of cyclosporin were analysed using HPLC. Results: The mean peak plasma cyclosporin concentration of 654.4ng/ml was observed at 3.39h with test brand and was similar to that of reference brand with Cmax of 628.61ng/ml at 3.43h. The differences between the pharmacokinetic parameters of two brands of cyclosporin were statistically in significant. Conclusion: Both the brands of cyclosporin can be considered to be bioequivalent on the basis of the results obtained.