Cerebroprotective Effects of 2-Ethyl-6-methyl-3-hydroxypyridine-2,6-dichlorophenyl(amino)phenylethanoic Acid in the Treatment of Purulent Meningitis.

Purulent meningitis (PM) is a severe disease, characterized by high mortality and a formation of a residual neurological deficit. Loss of treatment of PM leads to the lethal outcome in 100% of cases. In addition, death and the development of residual neurological complications are possible despite adequate therapy. The aim of the study was to evaluate the cerebroprotective effects of a new pharmacological compound 2-ethyl-6-methyl-3-hydroxypyridine-2,6-dichlorophenyl(amino)phenylethanoic acid (EMHDPA) on the bacterial purulent meningitis in a model of experimental pneumococcal meningitis. Meningitis was simulated by intrathecal injection of the suspension containing Streptococcus pneumoniae at the concentration of 5 × 109 CFU/mL. The cerebroprotective effect was evaluated by survival rates, the severity of neurological deficit, investigatory behaviors, and results of short-term and long-term memory tests. The group administered with EMHDPA showed high survival rates, 80%. Animals treated with the studied compound showed a higher clinical assessment of the rat health status and specific force, and a lesser intensity of neurological deficit compared to the control group (p < 0.05). Locomotor activity of the animals treated with EMHDPA was significantly higher compared to the control group (p < 0.05). There is a decrease in the activity of all estimated indicators of oxidative stress in the group administered with 2-ethyl-6-methyl-3-hydroxypyridine-2,6-dichlorophenyl(amino)phenylethanoic acid relative to the control group: a decrease in the activity of catalase-17%, superoxide dismutase-34%, malondialdehyde and acetylhydroperoxides-50%, and nitric oxide-85% (p < 0.05). Analysis of the data obtained during the experiment leads to the conclusion about the effectiveness of 2-ethyl-6-methyl-3-hydroxypyridine-2,6-dichlorophenyl(amino)phenylethanoic acid in the treatment of the experimental PM.

Erythropoietin Mimetic Peptide (pHBSP) Corrects Endothelial Dysfunction in a Rat Model of Preeclampsia.

Preeclampsia is a severe disease of late pregnancy. Etiological factors and a pathogenetic pattern of events still require significant clarification, but it is now recognized that a large role is played by placentation disorders and emerging endothelial dysfunction. The administration of short-chain peptides mimicking the spatial structure of the B erythropoietin chain may become one of the directions of searching for new drugs for preeclampsia prevention and therapy. Simulation of ADMA-like preeclampsia in Wistar rats was performed by the administration of a non-selective NOS blocker L-NAME from the 14th to 20th day of pregnancy. The administration of the pHBSP at the doses of 10 µg/kg and 250 µg/kg corrected the established morphofunctional disorders. The greatest effect was observed at a dose of 250 µg/kg. There was a decrease in systolic and diastolic blood pressure by 31.2 and 32.8%, respectively (p < 0.0001), a decrease in the coefficient of endothelial dysfunction by 48.6% (p = 0.0006), placental microcirculation increased by 82.8% (p < 0.0001), the NOx concentration was increased by 42,6% (p = 0.0003), the greater omentum edema decreased by 11.7% (p = 0.0005) and proteinuria decreased by 76.1% (p < 0.0002). In addition, there was an improvement in the morphological pattern of the fetoplacental complex and the ratio of BAX to Bcl-2 expression which characterizes the apoptotic orientation of the cells.

Studies to Elucidate the Effects of Furostanol Glycosides from Dioscorea deltoidea Cell Culture in a Rat Model of Endothelial Dysfunction.

Currently, there is no doubt surrounding a theory that the cardiotropic effects of sex hormones can be due to their direct effect on the cardiovascular system. In recent years, interest in the study of steroid glycosides has increased. We studied the effects of furostanol glycosides (protodioscin and deltozid) from the cell culture of the Dioscorea deltoidea (laboratory code DM-05) on the physiological and biochemical parameters of vascular endothelial function in hypoestrogen-induced endothelial dysfunction after bilateral ovariectomy. It was shown that the use of DM-05 at a dose of 1 mg/kg makes it possible to prevent the development of arterial hypertension (the level of systolic blood pressure (SBP) decreases by 9.7% (p < 0.05) and diastolic blood pressure (DBP) by 8.2%), to achieve a decrease in the coefficient of endothelial dysfunction by 1.75 times against the background of a hypoestrogenic state. With DM-05, an increase in the concentration of stable nitric oxide metabolites (NOx) by 45.6% (p < 0.05) and an increase in mRNA endothelial nitric oxide synthase (eNOS) expression by 34.8% (p < 0.05) was established, which indicates a positive effect of furostanol glycosides on the metabolism of nitric oxide after ovariectomy. Positive dynamics in the histological structure of the heart and the abdominal aorta indicate the pronounced endothelio- and atheroprotective effects of DM-05.

Arginase inhibitor in the pharmacological correction of endothelial dysfunction.

THIS PAPER IS ABOUT A WAY OF CORRECTION OF ENDOTHELIAL DYSFUNCTION WITH THE INHIBITOR OF ARGINASE: L-norvaline. There is an imbalance between vasoconstriction and vasodilatation factors of endothelium on the basis of endothelial dysfunction. Among vasodilatation agents, nitrogen oxide plays the basic role. Amino acid L-arginine serves as a source of molecules of nitrogen oxide in an organism. Because of the high activity of arginase enzyme which catalyzes the hydrolysis of L-arginine into ornithine and urea, the bioavailability of nitrogen oxide decreases. The inhibitors of arginase suppress the activity of the given enzyme, raising and production of nitrogen oxide, preventing the development of endothelial dysfunction.