Recent epidemiological studies implicated left ventricular hypertrophy (LVH) as a premonitory symptom of mortality from many cardiovascular complications. Although hypertrophy by a chronic overload per se is not a pathological rather biological adaptive response of heart, in conditions such as essential hypertension, valvular heart diseases and myocardial infarction, but heart failure as a final form of hypertrophy is an obvious disease causing high mortality. Qualitative changes in genomic expression allow the hypertrophied cardiac fibre to develop a normal active tension to the increased load at the expense of its maximal shortening velocity (V-max), which are preceded by the temporary expression of protooncogenes, isogenes of proteins of contractile apparatus and the re-expression of "fetal" isoforms. In recent years it has become clear that a variety of hormones are present in the heart and may participate in the genesis of cardiac hypertrophy. However, the molecular mechanisms remain unknown. Mechanical load or stretch of cardiac tissues has been identified as a growth stimulus, and humoral mechanisms such as the renin-angiotensin system and the sympathetic nervous system have been suggested to play a role in the regulation of cardiac cell growth and hypertrophy. Atrial natriuretic factor, nitric oxide and prostanoids may negate and balance the actions of various ionotropic agents. H-ras, G-proteins, protooncogenes and trans acting factors have been identified for signal transduction in the regulation of cardiac gene program and hypertrophy.

Toad (Bufo melanostictus) skin a rich source of bioactive compounds, was explored for possible pharmacological effects on experimental animals. The LD50 of toad skin extract (TSE) was found to be 400 mg/kg, (iv) in male albino mice. TSE produced significant hyperthermia and potentiated pentobarbitone induced sleeping time in male albino mice. TSE produced apnoea in cat and rat. It produced a biphasic response, hypotension followed by hypertension in cat and the latter action was blocked by atropine. On isolated heart of guinea pig TSE produced negative chronotropic, positive ionotropic effect and produced reversible blockade of guinea pig auricular contraction. Atropine blocked TSE induced contractile response on guinea pig isolated ileum and rat fundus. Electrical stimulation induced twitch response of chick isolated biventer cervices was inhibited by TSE but it had no effect on the isolated rat phrenic nerve diaphragm preparation. TSE did not possess haemorrhagic activity but produced strong haemolytic activity.

The present study attempts to investigate the interactions of alpha-adrenoceptors with various agonists. In isolated ventricle preparations obtained from rats chronically treated with prazosin there was a decrease in the pD2 value of nor-adrenaline (NA) and no change in maximal response suggesting that calcium fluxes do not play a role. However, with yohimbine there appeared to be a down regulation of the alpha, receptor. In hypertensive rats there was an increase in the pD2 value of NA and terbutaline (TA) with no change (NA) or increase (TA) in maxima suggesting increase in beta, receptor and increased calcium influx. The pD2 value of NA was reduced with chronic prazosin treatment which is in line with that observed in normotensive preparation. The increase in the pD2 value in hyperthyroid rat preparations may be due to thyroid hormone induced changes in various receptor effector coupling factors. Simultaneous treatment with alpha- adrenoceptor blockers suggest increase in alpha, receptor density and increase in calcium influx with NA. In aortic strip preparations chronic prazosin treatment abolished responses to NA and phenylephrine (PE) which could simply be due to alpha, blocking action of prazosin. However, the increase in pD2 value of NA and PE suggest that this could be due to block of presynaptic alpha, receptors. In DOCA-saline hypertensive rats chronic treatment with prazosin reduced the pD2 value and maxima of NA and abolished that of PE which is in line with the known mechanism of prazosin. With chronic yohimbine treatment the increase in pD2 value of PE may be due to the inhibitory action of alpha, receptors. The changes seen in the hyperthyroid rats or in those simultaneously treated with alpha adrenoceptor blocker may be secondary to the primary effect on the heart and due to generalised reduced sensitivity of the rat aorta.

Amphotericin B remains the drug of choice in most systemic mycoses, but its use is often limited by its severe side effects. Liposomal encapsulation of amphotericin B has been shown to improve tolerance without compromising efficacy. In this study, the dosage regimens and frequency of administration of liposomal amphotericin B prepared using soya phosphatidylcholine and cholesterol given prophylactically or therapeutically in mice infected with Aspergillus fumigatus was assessed. Liposomal amphotericin B was more effective than free amphotericin B on an equal dose basis when given therapeutically. A large single dose of liposomal amphotericin B was more effective, both prophylactically and therapeutically, than two divided doses of the total dose.

Effect of riboflavin supplementation on glutathione and glutathione redox cycle in selenite induced cataractous rat lenses was studied, as the lens negates some of the toxic effects of the oxidants by its glutathione mediated defence mechanisms. The alterations in the level of proteins, reduced glutathione (GSH) and the activity of (-glutamylcysteine synthetase ((-GCS), glutathione reductase (GR) and glutathione peroxidase (GSH-Px) have been studied in the control and riboflavin supplemented rats. The cataractous littermates supplemented with riboflavin showed increased activity of the enzymes and elevated levels of metabolites as compared to the cataractous, non-supplemented littermates. The results of this study point towards the role of riboflavin in the prevention of cataract, induced by selenite.

The effect of picroliv, an iridoid glycoside mixture from the roots and rhizome of Picrorhiza kurrooa, on ethanol induced toxicity in isolated rat hepatocytes was investigated by following changes in marker enzymes (GOT, GPT, alkaline phosphatase, and aldehyde dehydrogenase) in hepatocytes. The level of all the enzymes was reduced significantly following incubation of rat hepatocytes with 40 'l/ ml of 40% ethanol solution at 37ø C for 24 hours. Picroliv, showed a significant dose dependent preventive effect on alcohol-induced hepatocyte toxicity. The results were compared with other putative hepatoprotective agents such as andrographolide, silymarin, and catalpol.

5-hydroxytryptophan (5-HTP), a precursor of serotonin and para chlorophenylalanine (PCPA), a serotonin synthesis blocker, were administered centrally in immunized rats to investigate the role of central serotonergic system in immunomodulation. 5-HTP treatment prior to immunization significantly inhibited the cell mediated as well as humoral immune response. However, plasma corticosterone levels remained unaffected. Post-immunization treatment with 5-HTP did not produce any effect on immune response and plasma corticosterone levels. PCPA administered prior to immunization markedly stimulated the cell-mediated as well as humoral immune response but there was no effect on plasma corticosterone levels.Cell mediated immune response was, however, reduced significantly with a concomitant increase in the plasma corticosterone levels in the rats treated with PCPA after immunization. It is suggested that the central serotonergic system plays a critical role in immunomodulation.

The wound healing effect of aqueous extract of the latex of Euphorbia neriifolia was evaluated in guinea pig. Surgically produced cutaneous wounds were treated with topical application of 0.5% and 1 .O% sterile aqueous solution of the extract. The extract facilitated the healing process as evidenced by increase in tensile strength, DNA content, epithelization and angiogenesis.

The effect of lyophylized aqueous extract of Alstonia boonei stem bark was investigated on guinea pig ileum and rat stomach strip. The extract had a contractile effect on both smooth muscles; the effect was more on rat stomach strip than on guinea pig ileum. Pre-incubation of the stomach strip preparation did not inhibit the extract induced tonic contractions. On the other hand, the contraction induced by the extract was antagonised by methysergide in a competitive manner suggesting a role for 5-HT in the biological effect of the extract.

In the present study, ethinyl estradiol (EE) was administered chronically at a dose of 1.5 mg/ kg/ day intramuscularly to rats for 3 weeks and the sensitivity of isolated aortic strip and portal vein to nor-adrenaline (NA) was studied. Chronic EE treatment did not alter the pD2 values of NA in isolated aortic strip; however, it produced significant increase in pD2 values of NA in portal vein preparation. Chronic EE treatment did not alter the aortic relaxation. It is concluded that chronic EE treatment of rat results in supersensitivity of portal vein to NA, which may be prejunctional in nature.

Anti-arthritic and anti-inflammatory action of a poly-herbal formulation (Ease(r)) was compared with standard anti-inflammatory drugs in different in vivo and in vitro test models. Treatment with Ease(r) significantly reduced adjuvant-induced non- established and established arthritis in rats and the effect was comparable to phenylbutazone. It also provided significant protection against protein denaturation and RBC membrane damage in the in vitro models, Results were comparable to acetyl salicylic acid. Ease(r) also exhibited significant proteinase inhibitory action. It is concluded that Ease(r) may prove to be a useful anti-arthritic product in future.

Three compounds of phenoxypropanolamine type with chlorine substituted at para (Compound I: PCP) and ortho (Compound II: OCP) positions and without chlorine (Compound III: NCP) were synthesised and characterised by their physical and chemical methods. All the three compounds significantly (P<0.001) reduced the tachycardia induced by isoprenaline in dogs and rats while compound I and compound II significantly (P<0.001) blocked the isoprenaline induced fall in blood pressure implying a non-selective beta, and beta, blocking effect in both species. Compound III did not block the isoprenaline induced fall in blood pressure in both the animals implying a selective beta, action. The blockade produced by compound I & II (2 x 10-6 M) were similar to the effect produced by propranolol (2 x 10-6 M).

. Levamisole hydrochloride in low concentration (5 ng/mI) stimulated the movements of the whole worm as well as of the nerve-muscle complex of Setario cervi suspended in an isolated organ bath. At higher concentration (25 ng/mI) the response was biphasic consisting of initial stimulation followed by irreversible paralysis. The initial stimulant effect is not due to release of ACh as it is not blocked by prior addition of d-tubocurarine to the bath fluid. Levamisole in 5 x 25 mg/kg daily dose caused disappearance of microfilariae from the peripheral circulation in 7 of the 8 rats treated: The drug at this dose level had some macrofilaricidal action as well. A higher dose of 5 x 50 mg/kg daily caused complete disappearance of microfilariae from peripheral circulation of all the rats and produced a significant lethal effect on the adult worms The antifilarial efficacy of the drug needs evaluation in domestic animals and men.