Histopathological lesions in encephalon and heart of mice infected with Toxoplasma gondii increase after Lycopodium clavatum 200dH treatment.

In many cases, symptoms of toxoplasmosis are mistaken for the ones of other infectious diseases. Clinical signs are rare in immunocompetent people. However, when they arise, in the acute phase of infection, several organs are affected due to the rapid spread of tachyzoites through the bloodstream. In the present study, the reduction of tachyzoites in peripheral blood of mice of G72 (infected 72h after treatment) and G48 (infected 48h after treatment and treated three more times), when compared with IC (infected and non-treated), suggests protective effect exerted by Lycopodium clavatum. If on the one hand L. clavatum brought benefits, reducing parasitemia, on the other hand, the parasitism became exacerbated. Histopathological analysis demonstrated focal, multifocal and diffuse inflammatory infiltrates, ranging from absent, discreet, moderate to intense, in heart and encephalon of mice of NIC (non-infected and non-treated), IC, G48 and G72 groups, respectively. In the perivascular region and meninges, the injuries were enlarged. The presence of tachyzoites was demonstrated through immunohistochemical (IHC) assay in myocardium. Toxoplasma gondii induced increase of collagen fibers in myocardium of mice of G72 and G48 groups, compared with IC (p<0.05) and NIC (p<0.001). The presence of inflammatory infiltrates, as well as the progressive fibrosis, caused myocardial remodeling in animals treated with L. clavatum. Counterstaining with H&E suggests TGF-ß expression by mononuclear cells in the inflammatory infiltrate. Based on our results, we can conclude that the adopted regimen and potency exerted a protective effect, reducing parasitemia. However, it intensified the histopathological lesions in encephalon and heart of mice infected with T. gondii.

Effect of isoflavone extracts from Glycine max on human endothelial cell damage and on nitric oxide production.

OBJECTIVE: In this study, we determined the protective effect of isoflavones from Glycine max on human umbilical vein endothelial cell (ECV304) damage induced by hydrogen peroxide (H2O2) and on nitric oxide (NO) production. METHODS: We studied the regulation of NO synthesis in cultured human endothelial cells by phytoestrogens contained in soy extracts in the presence or absence of ICI 182,780 or N(omega)-nitro-L-arginine methyl esther and determined the protective effect of these isoflavones on ECV304 damage induced by H2O2. RESULTS: We show that soy extracts activate NO synthesis in endothelial cells and protect against cell damage. CONCLUSIONS: In conclusion, soy isoflavones markedly protect ECV304 cells against H2O2 damage and promote NO synthesizing. Therefore, these isoflavones can potentially act as an NO promoter and as an antioxidant.

Pimaradienoic acid inhibits vascular contraction and induces hypotension in normotensive rats.

The present investigation was designed to investigate the effect of the diterpene ent-pimara-8(14),15-dien-19-oic acid (pimaradienoic acid, PA) on smooth muscle extracellular Ca(2+) influx. To this end, the effect of PA on phenylephrine- and KCl-induced increases in cytosolic calcium concentration ([Ca(2+)](c)), measured by the variation in the ratio of fluorescence intensities (R340/380 nm) of Fura-2, was analysed. Whether bolus injection of PA could induce hypotensive responses in conscious normotensive rats was also evaluated. PA inhibited the contraction induced by phenylephrine (0.03 or 10 micromol L(-1)) and KCl (30 or 90 mmol L(-1)) in endothelium-denuded rat aortic rings in a concentration dependent manner. Pre-treatment with PA (10, 100, 200 micromol L(-1)) attenuated the contraction induced by CaCl(2) (0.5 nmol L(-1) or 2.5 mmol L(-1)) in denuded rat aorta exposed to Ca(2+)-free medium containing phenylephrine (0.1 micro mol L(-1)) or KCl (30 mmol L(-1)). Interestingly, the inhibitory effect displayed by PA on CaCl(2)-induced contraction was more pronounced when KCl was used as the stimulant. Phenylephrine- and KCl-induced increases in [Ca(2+)](c) were inhibited by PA. Similarly, verapamil, a Ca(2+)-channel blocker, also inhibited the increase in [Ca(2+)](c) induced by either phenylephrine or KCl. Finally, bolus injection of PA (1-15 mg kg(-1)) produced a dose-dependent decrease in mean arterial pressure in conscious normotensive rats. The results provide the first direct evidence that PA reduces vascular contractility by reducing extracellular Ca(2+) influx through smooth muscle cellular membrane, a mechanism that could mediate the hypotensive response induced by this diterpene in normotensive rats.