Physical Fatigue and Morphofunctional State of the Myocardium in Experimental Chronic Stress.

The relationship between the development of skeletal muscle fatigue of a specific type in male Wistar rats and morphofunctional alterations in the myocardium in the posttraumatic stress disorder (PTSD) model has been investigated for the first time. The aggravation of oxidative stress in the cardiomyocytes and the related transformation of the cell structural components and the depletion of energy reserves in PTSD has been identified as one of the main factors that accelerate the onset of musculoskeletal fatigue.

Effects of a compound from the group of substituted thiadiazines with hypothermia inducing properties on brain metabolism in rats, a study in vivo and in vitro.

The aim of the present study was to examine how administration of a compound of 1,3,4- thiadiazine class 2-morpholino-5-phenyl-6H-1,3,4-thiadiazine, hydrobromide (L-17) with hypothermia inducing properties affects the brain metabolism. The mechanism by which L-17 induces hypothermia is unknown; it may involve hypothalamic central thermoregulation as well as act via inhibition of energy metabolism. We tested the hypothesis that L-17 may induce hypothermia by directly inhibiting energy metabolism. The study in vivo was carried out on Sprague-Dawley adult rats. Two doses of L-17 were administered (190 mg/kg and 760 mg/kg). Brain metabolites were analyzed in control and treated groups using magnetic resonance spectroscopy, along with blood flow rate measurements in carotid arteries and body temperature measurements. Further in vitro studies on primary cultures from rat hippocampus were carried out to perform a mitochondria function test of L-17 pre-incubation (100 µM, 30 min). Analysis of brain metabolites showed no significant changes in 190 mg/kg treated group along with a significant reduction in body temperature by 1.5°C. However, administration of L-17 in higher dose 760 mg/kg provoked changes in brain metabolites indicative of neurotoxicity as well as reduction in carotid arteries flow rate. In addition, a balance change of excitatory and inhibitory neurotransmitters was observed. The L-17 pre-incubation with cell primary cultures from rat brain showed no significant changes in mitochondrial function. The results obtained in the study indicate that acute administration of L-17 190 mg/kg in rats induces mild hypothermia with no adverse effects onto brain metabolism.

The impact of immunomodulator compound from the group of substituted thiadiazines on the course of stress reaction.

A significant role of the stress response to many different diseases prompted a search for new specialized and non-specialized anti-stress agents. This study examines the effect of the compound L17 from the group of 5-phenyl substituted-6H-1,3,4-thiadiazine-2-amines, on the manifestations of the stress response. The authors used a standard model of immobilization stress, in which an animal was immobilized on its back for 6h a day. Parameters of the morphological and functional states of the organs studied were measured and biochemical and enzyme-immunoassays were carried out on the first and second days. This study reveals that the main mechanism by which the L17 compound mediates of its anti-stress was by activation of macrophages on the second day of the experiments and the inhibition of apoptosis in the thymus. The results enable us to suggest that the compound L17 does not improve resistance to stress; however, it does lower the reaction to stress.

Morphological restructuring of myocardium during the early phase of experimental diabetes mellitus.

The purpose of this study was to determine the specific features of the morphological restructuring of the myocardium in the early stage of experimental diabetes mellitus (DM). Experimental type 1 DM rat model was developed by intraperitoneal injection of alloxan solution at a dose of 30 mg per 100 g body mass. After 1 month, 3 mL of blood was drawn by heart puncture and the plasma separated by centrifugation for biochemical analysis. Plasma glucose, insulin, and glycosylated haemoglobin in whole blood were determined. Light microscopy and morphometric studies were conducted of histological slices of the hearts of experimental animals. The investigation of heart morphology showed a statistically significant alteration in chamber wall thickness in the right auricle in rats with alloxan-induced DM. A change in cardiomyocyte diameter in myocardium slices was observed in all chambers of DM rats except for the left ventricle. Average cardiomyocyte diameter in rats with experimental DM increased by 26.6% and 15.5% in the right auricle and right ventricle, respectively, while average cardiomyocyte diameter in the left auricle decreased by 20.8%. Histological investigation of the heart following alloxan injection demonstrated, under the epicardium, distended vessels of the venous collecting microcirculatory system. Aggregation and agglutination of red blood cells and endothelial cell destruction were found in some vessels. In the early stage of DM development, structural alterations in the microcirculatory channels and myocardiocytes can be observed in the heart. These structural alterations were most evident in the right chambers of the heart.

Modulation of inflammatory response improves myocardial infarct healing in rats.

It is reputed that the ideal therapeutic approaches to treatment of patients with acute coronary syndrome (ACS) and myocardium infarction (MI) should be aimed at the inflammation reaction triggers. This study investigated the effectiveness of the impact of L- 17 compound of the group of 5- phenyl substituted-6H-1,3,4-thiadiazine-2-amines upon the course of experimental MI as compared to the impact of a preparation, officially registered in Russia as an immunomodulator, Tamerit, belonging to phthalhydrazid derivative substance. Acute MI in rats was induced by left coronary artery coagulation. Histological study of the myocardium sections and biochemical analysis has been carried out at the 1st and 7th days of the experimental MI. The conducted investigations have shown that under the action of immunocorrectors the inflammation reaction character changes, exudative/destructive inflammation is replaced by a proliferative-cellular one. Animals' blood biochemical analysis at the background of L-17 and Tamerit introduction has shown a decrease of aminotransferases and lactatedehydrogenases activity in blood as compared to the reference group of animals' indicators, which is evidently caused by epicardial injury of myocardium and lesser amount of the alternative cardiomyocytes. At the same time, no noticeable difference in biochemical characteristics in groups, having been treated to immunomodulators of different chemical composition was identified, which is the sign of the essential similarity of their impact. Thus, immunocorrectors of different chemical groups (Tamerit and compound L17) diminish the volume of initial myocardial infarction and accelerate the granulation processes in course of MI, and represent a new category of treatment agents.