Mechanisms of neuronal calcium homeostasis destabilization caused by hyperstimulation of glutamate receptors

The present paper summarizes the data obtained in studying the mechanisms of glutamate-induced deterioration of neuronal Ca2+ homeostasis. In the cultured mammalian central neurons, a short-term (< 1 min) glutamate (GLU, 100 mu) challenge is known to induce a readily reversible (transient) neuronal [Ca2+]i increase. In contrast, a long-term (15-30 min) GLU exposure leads to the appearance of high [Ca2+]i plateau or to the partial recovery of the increased [Ca2+]i. Experiments show that impaired [Ca2+]i recovery in the postglutamate period cannot be explained by the increased [Ca2+]i permeability of the neuronal membrane, as earlier considered. Moreover, a sustained elevation of [Ca2+]i during and after chronic GLU application is associated with a progressive decrease in Ca2+ permeability. The major cause of GLU-induced Ca2+ overload is the mitochondrial depolarization resulted from excessive Ca2+ influx into the mitochondria, the generation of free radicals and the opening of a "giant pore" in the inner mitochondrial membrane. This in turn suppresses both ATP synthesis and Ca2+ electrophoretic uptake into the mitochondrial matrix. In combination with [Ca2+]i-dependent acidification, this leads to the suppression of Ca2+ release from the cell via Na+/Ca2+ exchanger and Ca2+/H+ pump of the neuronal membrane. Therefore, [Ca2+]i recovery following a long-term GLU treatment becomes strongly or even irreversibly compromised.     

The changes of lipids, lipoproteins and apolipoproteins in plasma in ischemic stroke

Contents of lipids (cholesterol CS, triglycerides) as well as levels of CS of lipoproteins of different density and of apolipoproteins A1 and B were measured in blood serum of 31 patients in different periods after of ischemic stroke. The majority of the indices studied were significantly decreased in men in acute periods of the stroke, especially in 8-21 days after the stroke development. Meanwhile, the levels of lipids, CS lipoproteins of both low and very low densities were increased later. Contents of CS of antiatherogenic lipoproteins of high density (HDLP) was low in different periods after the development of disorders of cerebral circulation. This confirms the concept that low level of HDLP is one of the risk factors of ischemic stroke. Decrease of the levels of both lipids and CS of lipoproteins of different density was more pronounced in patients with more severe atherosclerotic damages of the main cerebral arteries. Disorders of metabolism of lipoproteins in ischemic disorders of cerebral circulation are discussed with reference to literary data taking into consideration their heterogeneity. Genetically determined pathology of certain apolipoproteins plays a key role factor in the development of early atherosclerosis and in the elucidation of biochemical markers of the primary damages of cerebral vessels.     

The current course and treatment of infectious endocarditis

Clinical study of 172 patients treated in the Burdenko Military Hospital for subacute infectious endocarditis in 1980-1996 compared with 192 cases in 1950-1979. Contemporary course of the disease is attended by a few symptoms, primordiality and single-valve affection. On the grounds of antibiotics sensitivity of the most prevalent infection agents discovered in 1996, the article develops some schemes of antibacterial therapy for Streptococcus, Enterococcus and staphylococcal etiology of disease. Rational antibiotic therapy together with surgery measures reduced lethality to 14.3% for Streptococcus endocarditis, to 16.7%--for Enterococcus and to 34.4%--for Staphylococcus.     

Abnormal mitochondrial function in myocardium of dogs with chronic heart failure

Chronic heart failure (HF) is associated with morphologic abnormalities of cardiac mitochondria that include hyperplasia, reduced organelle size and compromised structural integrity. In the present study, we examined mitochondrial respiration in myocardium of 10 normal dogs and 10 dogs with chronic HF (LV ejection fraction 24+/-2%) produced by intracoronary micro-embolizations. Mitochondrial respiratory rates were determined using a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles. Basal respiratory rate (VO), respiratory rate after addition of substrates, glutamate and malate (VSUB) and state 3 respiratory rate (VADP, after addition of ADP), were measured in tissue samples from the subendocardial and subepicardial LV free wall, interventricular septum and right-ventricular free wall. No differences were observed in basal respiratory rates between normal and HF tissue, while VSUB was significantly lower in HF compared to normal. VADP was 50-60% lower in HF compared to normal tissue (P<0.001). The results indicate abnormal mitochondrial respiratory activity in myocardium of dogs with chronic HF. These findings support the concept of low myocardial energy production in HF that can contribute to the global cardiac dysfunction.     

Comparative cytologic study of nephron structure in higher vertebrates

A comparative study of the cytological characteristics of the epithelial lining of the nephron and collecting tubules was performed in 9 species of reptiles, 19 species of birds and 12 species of mammals. Representatives of each class of higher vertebrates were shown to have certain specific features of the epithelial lining of different parts of the nephron. Differentiation of various areas of the proximal part of the nephron proceded in phylogeny with different intensity and the maximum specialization was characteristic of the most proximal portion of this part of the nephron. In the cells of the proximal parts of nephrons of some reptiles there were phenomena of apocrine secretion. Evolution of the distal part of the nephron developed to form a loop and differentiation of the distal convoluted segment. The higher differentiation of the epithelial lining of the nephron distal part in birds and mammals, unlike in reptiles, seems to be associated with a more considerable functional specilization of this part. In the cytochemical characteristics of the epithelium of the uriniferous and collecting tubules of kidneys of higher vertebrate animals there are common regularities in the distribution of RNA, proteins and some enzymes. The polysaccharide content is maximum in the epithelial cells of kidneys of reptiles.