In an attempt to determine the possible mechanism(s) behind the antileishmanial activity of zinc sulphate, promastigotes, axenic amastigotes and intracellular amastigotes of both Leishmania major and L. tropica were incubated with different concentrations of the compound. For each of the two Leishmania species, all three forms were found to be inhibited by the zinc sulphate, in a dose-dependent manner, the promastigotes being the most resistant form, followed by the axenic amastigotes. These results indicate that zinc sulphate has a direct antileishmanial effect. Compared with macrophages from starch-treated mice, the macrophages recovered from mice that had been injected intraperitoneally with zinc sulphate (daily for the 4 days prior to the macrophage collection) or BCG (once, 4 days before the cell collection) showed increased phagocytosis and increased killing of L. major and L. tropica. As the effects of the zinc sulphate were not statistically different from those of the known immunomodulating agent BCG, zinc sulphate appears to have an immunomodulating effect, in addition to its direct antileishmanial effect.

No abstract

When used in vitro, zinc sulphate has a direct antileishmanial effect. To see if this effect involved the inhibition of the parasites' enzymes, extracts of the promastigotes and axenic amastigotes of Leishmania major (MHOM/IQ/93/MRC6) and L. tropica (MHOM/IQ/93/MRC2) were prepared. Zinc sulphate, at various concentrations, was then added to samples of these extracts before the activities, in the samples, of certain key enzymes of the Embden-Meyerhof pathway, hexose-monophosphate shunt and citric-acid cycle, and of two enzymes associated with virulence (protease and acid phosphatase), were determined. The zinc was found to inhibit every enzyme investigated, usually in a dose-dependent manner. Thus the direct antileishmanial effect of zinc may result, partially or entirely, from the inhibition of enzymes that are necessary for the parasites' carbohydrate metabolism and virulence.

The protective effects of drugs acting at the benzodiazepine receptors against ethanol-induced gastric damage were investigated using a newly developed in vitro model of the ethanol-induced gastric damage. The rat stomachs were isolated from the whole animal and kept in Kreb's solution at 37 degrees C. Gastric damage was induced by administration of 1 mL of 50% V/V ethanol into the isolated rat stomach. Administration of the benzodiazepine agonist, clonazepam (25, 50, 100 microg), or the partial benzodiazepine inverse agonist Ro15-4513 (50 or 100 microg), significantly protected against ethanol-induced gastric damage when these agents were administered 15 min before ethanol. The protective effects of these drugs were blocked by the benzodiazepine receptor antagonist flumazenil (200-400 microg). Flumazenil alone was found to aggravate ethanol-induced gastric damage (200-400 microg). The results of this study give evidence for the involvement of central-type benzodiazepine receptors located in the stomach in the protective action of benzodiazepines against ethanol-induced gastric damage.

Ninety-five Iraqi patients with cutaneous leishmaniasis (CL) caused by Leishmania tropica at AL-Karama Hospital in Baghdad were included in this study. Sixty patients were with single sore and the remaining with multiple sores. The study also included 10 atopic patients and 30 healthy individuals as a control group. Cellular and humoral immune response at different stages of the disease activity (early and late) were evaluated by estimation of serum IFNc, IL-4 and total IgE antibodies using ELISA kits while, the detection of specific anti leishmanial IgE antibodies was done manually. Specific IgE antibodies were only detected in early CL (\2 months) patients 68 (71.57 %) while, were not detected in late CL, atopic and healthy controls 30 (100 %). The results also showed a positive relationship between this antibody and the number of sores. Th-2 predominates during the early stage of the disease then shifts to Th-1 that proceed in the late stage, but both cytokines increased in CL patients in comparison to control group. The immune response of CL infection is possibly regulated by both Th-1 and Th-2. Multiple sores patients showed an increase of anti leishmanial IgE (0.120 ± 0.014), total IgE (120.7 ± 39.58 IU/ml), IFN-c (87.4 ± 30.52 pg/ml) and IL-4 (63.70 ± 20.32 pg/ml) levels than single sore patients with mean value of 0.108 ± 0.14, 92.3 ± 35.23 IU/ml, 47.2 ± 27.80 pg/ml and 51.04 ± 15.0 pg/ml respectively. It can be presented also as ratio of INF-c/IL-4 = 1.37 which is greater than those for single sore 0.9. These results indicated that the immune response of multiple sores patient's is higher than that with single sores.