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. Anat Rec, 298:396–407, 2015. © 2014 Wiley Periodicals, Inc.     

Automated detection of heuristics and biases among pathologists in a computer-based system

The purpose of this study is threefold: (1) to develop an automated, computer-based method to detect heuristics and biases as pathologists examine virtual slide cases, (2) to measure the frequency and distribution of heuristics and errors across three levels of training, and (3) to examine relationships of heuristics to biases, and biases to diagnostic errors. The authors conducted the study using a computer-based system to view and diagnose virtual slide cases. The software recorded participant responses throughout the diagnostic process, and automatically classified participant actions based on definitions of eight common heuristics and/or biases. The authors measured frequency of heuristic use and bias across three levels of training. Biases studied were detected at varying frequencies, with availability and search satisficing observed most frequently. There were few significant differences by level of training. For representativeness and anchoring, the heuristic was used appropriately as often or more often than it was used in biased judgment. Approximately half of the diagnostic errors were associated with one or more biases. We conclude that heuristic use and biases were observed among physicians at all levels of training using the virtual slide system, although their frequencies varied. The system can be employed to detect heuristic use and to test methods for decreasing diagnostic errors resulting from cognitive biases.     

Heavy–light chain interrelations of MS-associated immunoglobulins probed by deep sequencing and rational variation

The mechanisms triggering most of autoimmune diseases are still obscure. Autoreactive B cells play a crucial role in the development of such pathologies and, in particular, production of autoantibodies of different specificities. The combination of deep-sequencing technology with functional studies of antibodies selected from highly representative immunoglobulin combinatorial libraries may provide unique information on specific features in the repertoires of autoreactive B cells. Here, we have analyzed cross-combinations of the variable regions of human immunoglobulins against the myelin basic protein (MBP) previously selected from a multiple sclerosis (MS)-related scFv phage-display library. On the other hand, we have performed deep sequencing of the sublibraries of scFvs against MBP, Epstein–Barr virus (EBV) latent membrane protein 1 (LMP1), and myelin oligodendrocyte glycoprotein (MOG). Bioinformatics analysis of sequencing data and surface plasmon resonance (SPR) studies have shown that it is the variable fragments of antibody heavy chains that mainly determine both the affinity of antibodies to the parent autoantigen and their cross-reactivity. It is suggested that LMP1-cross-reactive anti-myelin autoantibodies contain heavy chains encoded by certain germline gene segments, which may be a hallmark of the EBV-specific B cell subpopulation involved in MS triggering.     

New insights in to the treatment of myocardial infarction

This study investigated the effects of the L-17 compound of the group of substituted 5R1, 6H2-1,3,4-thiadiazine-2-amines on the inflammatory cellular infiltration and myocardial remodelling which occurs after acute myocardial infarction (MI) in rats. The study is based upon recent clinical and experimental work which demonstrated the role of local and systemic inflammatory reactions in postinfarction remodelling. Acute MI in rats was induced by left coronary artery coagulation. Animals were sacrificed on day one, five and seven after MI induction. The myocardiumal samples were taken from all parts of the heart and examined by histology. This included areas of infarction, infraction and areas that were peri-infarctiom and left ventricular areas distant from the damaged tissues. Serum activity of creatine phosphokinase (CPK), aspartate aminotransferase (AST), isoenzymes 1 and 2 and lactate dehydrogenase (LDH1-2) were investigated on the same three days, before and in the process of MI development was investigated (at days 1, 5 and 7). The L-17 compound to not only decreased the area of initial infarction but also changed the pattern of inflammatory reaction in the affected myocardium fundamentally. Laboratory studies of effects of L-17 compound on the development and course of experimental MI showed that administration decreased blood AST and CPK levels significantly and provided useful the data about the correlation between the activity of these enzymes and the dimensions of the significantly necrotic area. In this model of experimental MI the use of the L-17 compound induced led to the replacement of the exudative destructive inflammation that is seen under standard conditions with a more cellular "productive" pattern of inflammation, with associated reduction in initial necrosis area and the, decrease in myocardial ischaemia and reperfusion injury may account for the accelerated repair process.     

Chronic administration of serotonin transporter inhibitor (fluoxetine) decreases monocrotaline-induced pulmonary hypertension in rats

The effect of a chronic fluoxetine treatment on the development of monocrotaline-induced pulmonary hypertension has been studied in rats. It was found that fluoxetine decreased right ventricular hypertrophy and reduces pulmonary vessels thickness. These results suggest that chronic fluoxetine treatment can lead to a decrease in the manifestation of pulmonary hypertension symptoms.     

Lipid peroxidation during cardiac remodeling in 12-month-old rats with experimental infarction

Blood serum was from 12-month-old Wistar rats with experimental myocardial infarction caused by occlusion of the upper third of the left coronary artery was analyzed. The content of conjugated dienes by the 45th day after primary experimental myocardial infarction returned to normal and did not differ from that in intact animals of the same age group. MDA concentration in rats of the treatment group was lower compared to normal. It was demonstrated that normalization of LPO was accompanied by significant exhaustion of the endogenous antioxidant system (SOD and catalase). Our results suggest that special therapy is required for correction of the endogenous antioxidant defense system.