Effect of Candida albicans septicemia on the cardiovascular function of rabbits.

Candida albicans is an opportunistic pathogen that causes life-threatening systemic infection in immunocompromised host. However, little is known about the effects of yeast on the cardiovascular functions. This study examined the effects of C. albicans septicemia on the heart and vessel functions and nitric oxide (NO) production in infected rabbits. Anaesthetized animals were challenged with intravenous C. albicans (6 x 10(8)/kg) or saline and the blood pressure of rabbits were measured over 5 h. After that response of the isolated thoracic aorta, right atrium and left papillary muscle were recorded. Blood pressure significantly decreased in the infected rabbits during the septicemia but in the control animals it was stable. The blood nitrite levels and NO-synthases (eNOS, iNOS) expression and tissue nitrite levels in the heart and aorta were similar in the both groups. In the aorta isolated from C. albicans-infected rabbits, acetylcholine-induced endothelium-dependent relaxation was decreased, but contractions induced by phenylephrine were potentiated. The NOS inhibitor, L-N(G)-nitro-arginine methyl ester (L-NAME)-induced contraction increase in the right atrium was depressed by the yeast-infection. In the heart and aorta, microscopic examination revealed no tissue invasion of C. albicans. These results indicate the ability of C. albicans-induced septicemia to destroy NO-related responses of the heart and aorta and may have important implications for functional damage to endothelium and the regulation of cardiovascular functions. In addition, NOS induction and NO over-production are not stimulated by systemic C. albicans infection, which would alter the host immune reaction and homeostasis.

Disulfonic stilbene prevents selenite-induced cataract in rat pup lens.

It is known that the subcutaneous injection of a single dose of sodium selenite into suckling rats results in the development of large nuclear opacities. The intracellular transport of selenite in various cells, except lens cells, occurs via the Cl/HCO3 exchanger. The aim of the present study is to investigate the possible role of the anion-exchange inhibitor, disulfonic stilbene (SITS), in the selenite-induced catarogenesis in the rat pups. Wistar albino rats (8-10 d old) were separated into three groups: one control and two experimental. The first experimental group was injected subcutaneously with a single dose of 30 nmol sodium selenite/g body weight. The second experimental group was injected with a single dose of 10 nmol SITS/g body weight 15 min before the same dose selenite injection. The control group did not have any injections. The stage of cataract development was examined on d 7 postinjection with slit-lamp photographs. In SITS pretreated group, all eyes remained transparent (considered as stage 0), whereas in the selenite-injected group, the animals did have different stage of nuclear cataract; 8 animals have stage 5, 10 animals have stage 4, and 4 animals have stage 3. A pretreatment of SITS completely prevented cataract formation of the selenite-induced cataract model in rat pups.

Prevention of selenite-induced opacification and biochemical changes in the rat pup lens through amiloride pretreatment.

PURPOSE: To determine the effects of amiloride on selenite-induced cataracts, to identify this agent's role as an anti-oxidant, and to study related effects on ion levels in the rat lens. METHODS: Wistar albino rat pups were assigned to one of three groups, one control and two experimental. The first experimental group (Group 1; n = 22) received a subcutaneous injection of sodium selenite (30 nmol/g body weight) on postpartum day 10. The second experimental group (Group 2; n = 21) received a subcutaneous injection of amiloride (1 nmol/g body weight) 15 minutes before the sodium selenite injection. The control group (n = 22) received no injection. The pups in each group were observed during three weeks after the injection date. At the end of this period, the stage of cataract development was identified by comparison with slit lamp photographs and then the pups were sacrificed and their lenses were removed intracapsularly using a posterior approach. Cation analysis was carried out and glutathione and malondialdehyde levels were measured for each group. RESULTS: Cataract stage in Group 1 was significantly higher than Group 2. Mean cataract stages in Groups 1 and 2 were 3.8+/-0.12 and 1.6+/-0.25 respectively. None of the control animals developed cataracts. Amiloride-pretreated group contained significantly higher glutathione levels than Group 1. The level of malondialdehyde in Group 1 lenses was approximately twice that in the lenses of the Group 2 amiloride+selenite-treated animals. The Ca(2+) level was significantly higher in Group 1 lenses compared to the amiloride-pretreated rats, but there was no significant difference between Groups 1 and 2 with regard to Na(+) and K(+) levels. CONCLUSION: Amiloride was very effective in preventing cataract formation in the selenite-induced cataract model. This protective effect of amiloride was accompanied by higher glutathione levels and lower malondialdehyde levels in the rat pups' lenses compared to levels in animals that received selenite alone. These results suggest an anti-oxidant role for this agent, in addition to its effects on lens ion homeostasis.

Inhibition of endothelium-dependent relaxation by Candida albicans.

This study examines the effects of Candida albicans on acethylcholine-induced, endothelium-dependent relaxation of thoracic aorta of rabbits, precontracted by phenylephrine (10(-7) M). Isolated vessel rings were incubated with C. albicans, Saccharomyces cerevisiae, or their mannans, and endothelium-dependent relaxation was measured by the induction of acethylcholine. Endothelium-dependent relaxation remained unaffected after 3 hours by either C. albicans or S. cerevisiae, or their mannans. After 24 hours, however, incubation with C. albicans had completely abolished relaxation, whereas relaxation was decreased by mannan of C. albicans and continued unaffected by S. cerevisiae. In contrast, no change was registered with a 24 hours incubation of C. Albicans in a sodium nitroprusside-induced, endothelium-independent, vascular smooth muscle relaxation. Microscopical investigation of the morphological structure of vessel walls revealed penetration of C. albicans on the intimal surface after 3 hours incubation and infiltration of the yeast through the vessel wall after 24 hours. No changes in vessel morphology occurred after 3 or 24 hours with S. cerevisiae or the mannan of C. albicans. These results show the ability of C. albicans to inhibit endothelium-dependent, but not endothelium-independent, relaxation of vascular smooth muscle and may have important implications for functional damage to endothelial cells and the regulation of vessel tone and blood flow.

Cardiac dysfunction induced by low and high diet antioxidant levels comparing selenium and vitamin E in rats.

The present study was designed to investigate and compare the effects of dietary antioxidants on the mechanical characteristics of the rat heart. Both sex weanling rats were fed for 12 to 14 weeks a standardized selenium (Se)- and vitamin E-deficient diet, a Se-excess diet, or a control diet. Deficiency or toxicity of Se was verified by direct (tissue Se analysis and histopathological investigations) methods. The hearts of both experimental groups revealed some alterations in contractile performance with increased heart rate and coronary perfusion pressure. The average peak contractile force of the electrically stimulated papillary muscle measured in both experimental groups was not significantly different from the control values. When expressed as a percentage, the maximal increase in the peak contractile force of papillary muscle (PCF) that was obtained with 100 nM isoproterenol, respectively, was less in both experimental groups (26% in PCF of deficient group; 34% in PCF of rich group) than in the control group (80% in PCF). A decreased stimulation of contractile force of papillary muscle strips by a beta-adrenergic agonist seems to be in agreement with possible alterations in the response to inotropic agents due to a modification of the receptor function.

The effect of selenium and vitamin E on microvascular permeability of rat organs.

The effects of dietary sodium selenite and vitamin E on the microvascular permeability of rat organs such as heart, brain, kidney, liver and eye were investigated by using the Evans blue leakage method. Combined deficiency of selenium and vitamin E caused an increase in the permeability of the heart and eye with respect to their controls while it had no considerable effect on the permeability of other organs. On the other hand, toxic levels of selenium (4.2 mg/kg) in diet decreased the permeabilities in kidney, liver, and eye whereas this parameter of brain increased in the same animal group. These results suggested that low or high sodium selenite and vitamin E contents in diet could alter the microvascular permeability of different organs in different manners. It might be important to give reasonable explanations for the pathophysiology of some diseases that are characterized with organ damage and/or disfunction originated from selenium deficiency or toxicity.

Possible mechanism of high calcium-induced relaxation of rabbit thoracic aorta.

1. The present study examined the effects of various agents on high calcium-induced relaxation of the rabbit thoracic aorta precontracted by phenylephrine (0.1 microM) or KCl (30 mM). 2. The vascular smooth muscle relaxation caused by high calcium was not changed in the presence of endothelium, glibenclamide (3 microM), TEA (5 mM), verapamil (1 microM), lidocaine (0.1 mM) and vanadate (0.1 mM). 3. In the presence of ouabain (0.1 mM) or potassium-free medium, high calcium-induced relaxation was completely abolished. 4. When rings were precontracted by high concentrations of phenylephrine (1 microM, 10 microM) and KCl (30 mM, 45 mM, 60 mM), calcium-induced relaxation was gradually decreased. 5. A low concentration of calcium ionophore A-23187 (0.1 microM) did not change calcium-induced relaxation, but A-23187 at a high concentration (1 microM) depressed this relaxation. 6. These results suggest that Na-K-ATPase activation could be responsible for high calcium-induced relaxation.