Metabolic transformation affected by specific Salmonella O antigen in the lymphocytes of salmonellosis patients

Metabolic transformation in the lymphocytes of salmonellosis patients, manifested by changes in the proportion of nucleic acids due to the stimulating action of Salmonella specific O antigen, was studied by the method of microspectral luminescent analysis. The level of single-helix nucleic acids in lymphocytes was shown to increase 6-8 hours after the stimulating action of specific O antigen, which was manifested by the increase of the alpha parameter from 0.21 to 0.68 in salmonellosis patients. This made it possible to confirm the diagnosis of salmonellosis in 92-95% of cases even at the early period of the disease when serodiagnosis could not yet be made.     

Elements of structural organization of the transcribed area of the ribosomal repeat (rDNA) in human peripheral blood lymphocytes

The rDNA transcribed region (TR) was tested for accessibility to RsaI recognizing 15 TR sites, DNase I, and photoinducible arylazide (N-(4-azido-2-hydroxybenzoyl)-N,N'-diaminoheptane acetate) in isolated nuclei and, with arylazide, in intact cells. Arylazide entered cells well and did not appreciably affect the chromatin structure. Its photolysis products efficiently modified DNA in accessible sites. Single-strand breaks made by DNase I were not transformed in double-stranded in rDNA TR, suggesting the necessity of denaturing electrophoresis for such an analysis. About 70% of all rDNA copies proved poorly inaccessible to endonucleases and arylazide, the accessibility being higher in their 18S and 5.8S rRNA gene regions than in the regions of the external transcribed spacers (ETSs) and the 28S rRNA gene. Proteinase K disrupted this structure, and the corresponding copies were extracted from nuclei. This explained why in situ hybridization occasionally fails to reveal rDNA in the nucleolar fibrillar center (FC) on electron microscopic preparations. In other rDNA copies, TR (excluding 5'-ETS) was accessible to nucleases and arylazide. These copies were not extracted from nuclei treated with proteinase K. Some of their RsaI sites were protected by tightly bound proteins. Seven such regions were identified in TR. Possible association of the molecular structure, nucleolar location, and functional state of rDNA is discussed.     

The N-stearoylethanolamine effect on the NO-synthase way of nitrogen oxide formation and phospholipid composition of erythrocyte membranes in rats with streptozotocine diabetes

The influence of N-stearoylethanolamine (NSE) on the NO-synthase way of NO generation and phospholipids composition of erythrocyte membranes of rats with streptozotocine-induced diabetes has been studied. It has been shown that the activation of iNOS activity, cNOS activity inhibition and increase of the stable NO metabolites content takes place in the red blood cells (RBC) of diabetic rats. The alterations were also found in the RBC membrane phospholipid content: a decrease of phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol, sphingomieline content and increase of phosphatidylethanolamine, phosphatidylcholine lysoforms level. The NSE suspension administration (50 mg/kg of body weight) to diabetic rats (3 months after the diabetes induction) resulted in iNOS activity inhibition, recovering of cNOS activity and normalization of NO stable metabolites level in RBC. The decrease of phospholipids lysoform levels, normalization of phosphatidylethanolamine, phosphatidylcholine content and increase of phosphatidylinositol level were found after NSE action.     

An overview of malaria transmission from the perspective of Amazon Anopheles vectors

In the Americas, areas with a high risk of malaria transmission are mainly located in the Amazon Forest, which extends across nine countries. One keystone step to understanding the Plasmodium life cycle in Anopheles species from the Amazon Region is to obtain experimentally infected mosquito vectors. Several attempts to colonise Ano- pheles species have been conducted, but with only short-lived success or no success at all. In this review, we review the literature on malaria transmission from the perspective of its Amazon vectors. Currently, it is possible to develop experimental Plasmodium vivax infection of the colonised and field-captured vectors in laboratories located close to Amazonian endemic areas. We are also reviewing studies related to the immune response to P. vivax infection of Anopheles aquasalis, a coastal mosquito species. Finally, we discuss the importance of the modulation of Plasmodium infection by the vector microbiota and also consider the anopheline genomes. The establishment of experimental mosquito infections with Plasmodium falciparum, Plasmodium yoelii and Plasmodium berghei parasites that could provide interesting models for studying malaria in the Amazonian scenario is important. Understanding the molecular mechanisms involved in the development of the parasites in New World vectors is crucial in order to better determine the interaction process and vectorial competence.     

Structure based virtual screening of ligands to identify cysteinyl leukotriene receptor 1 antagonist

Montelukast and Zafirlukast are known leukotriene receptor antagonists prescribed in asthma treatment. However, these fall short as mono therapy and are frequently used in combination with inhaled glucocorticosteroids with or without long acting beta 2 agonists. Therefore, it is of interest to apply ligand and structure based virtual screening strategies to identify compounds akin to lead compounds Montelukast and Zafirlukast. Hence, compounds with structures having 95% similarity to these compounds were retrieved from NCBI׳s PubChem database. Compounds similar to lead were grouped and docked at the antagonist binding site of cysteinyl leukotriene receptor 1. This exercise identified compounds UNII 70RV86E50Q (Pub Cid 71587778) and Sure CN 9587085 (Pub Cid 19793614) with higher predicted binding compared to Montelukast and Zafirlukast. It is shown that the compound Sure CN 9587085 showed appreciable ligand receptor interaction compared to UNII 70RV86E50Q. Thus, the compound Sure CN 9587085 is selected as a potent antagonist to cysteinyl leukotriene receptor 1 for further consideration in vitro and in vivo validation.     

Effect of N-stearoylethanolamine(NSE) on activity of angiotensine-converting enzyme in the brain structures and blood plasma of rats with streptozotocine-induced diabetes

The influence of saturated N-acylethanolamine--N-stearoylethanolamine (NSE) on the activity of angiotensine-converting enzyme (ACE) in the brain structures of rats with streptozotocine-induced diabetes was studied. It was shown that decreased activity of ACE was observed in the hypothalamus, increased--in the anterior pituitary. The NSE suspension administration to rats with experimental diabetes in a dose 50 mg/kg of body weight during 10 days caused a decrease in ACE activity in the anterior pituitary, whereas in the hypothalamus and hippocampus ACE activity did not change significantly. At the same time, introduction of NSE to intact animals led to the reduction of activity of ACE in the hippocampus, anterior pituitary and blood plasma. It is known that the highest amount of ACE in the brain structures is located in the membrane-bound state. Thus, the changes we have found in the activity of ACE in the control rats and in animals with induced diabetes may be related to the ability of NSE to the modulation of cell membranes lipid profile. Changes in the activity of ACE under the action of N-acylethanolamines may be one of the mechanisms for implementation of anti-hypertensive and anti-inflammatory action of these compounds.     

Study of endothelium-dependent blood oscillations in the human skin microcirculatory bed

Cutaneous microcirculation parameters were studied with laser Doppler flowmetry in healthy volunteers. To investigate endothelial-dependent peripheral blood flow oscillations the iontophoresis of 1% acetylcholine solution was carried out. To estimate the contribution of rhythmical components in blood flow signal the continuous wavelet-transform spectral analysis was used. To reveal correlation between microcirculation parameters under study the correlation analysis was used. The microcirculation index was shown to be the factor producing cross-correlation dependences. The only positive significant correlation between the blood flow oscillation amplitude in the range of endothelial activity normalized to mean microcirculation index at rest and maximal microcirculation index during the iontophoresis of acetylcholine was revealed.     

Modulation of human peripheral blood neutrophil apoptosis by ultraviolet C-range radiation and by gamma-irradiation

It was found that the irradiation with in vitro UVC (254 nm) in the dose range of 6-600 J/m2 accelerates the apoptosis of human peripheral blood neutrophils in a dose-dependent manner, with saturation occurring at UVC doses of 250-300 J/m2. gamma-Irradiation with a dose of 2 Gy accelerates the apoptosis of neutrophils, whereas the irradiation with doses of 10 and 20 Gy suppresses it (by 9 h of cultivation). Lipopolysaccharide (1 microgram/ml) suppresses the UVC-induced apoptosis of neutrophils.     

NO-dependent effects during adaptation of rats to intermittent hypoxia

In experiments on Wistar rats processes nitric oxide production on concentration of anions (NO2-, NO3-), carbamide and polyamines contents were investigated in processes of rats adaptation to acute hypoxia (7% O2 in N2, 30 min) and intermittent hypoxia training (10% O2 in N2, 15 min, 5 cycles daily) during 14 days. NO production by oxygen-dependent and oxygen-independent metabolites paths has been investigated. It is concluded that the disturbances in nitric oxide system induced by acute hypoxia by L-arginine injections may result in acute hypoxia.     

Effect of N-stearoylethanolamine on the level of stable NO metabolites in different pathological conditions which are accompanied by oxidative stress

The effects of N-stearoylethanolamine (NSE) at the level of stable NO metabolites--NO2- NO3- under different pathological conditions which were accompanied by oxidative stress and NO disbalance were studied. It was found that NSE promoted the increasing of NO metabolites level on the animal models with deficit of NO compared to control and evoked decreasing content of NO2- and NO3- under pathological conditions with NO overproduction. It is suppoused, that NSE effects could be determined, by its ability to modulate the the activity of NO-synthase izoformes.