Role of glycosaminoglycans in altering vascular wall permeability for atherogenic lipoproteins

The relationship between the pattern of distribution of lipoproteins and morphological features of atherosclerotic lesions was demonstrated by histoautoradiographic and histochemical methods in experiments using perfusion in vitro of aortas from atherosclerotic rabbits with atherogenic lipoproteins (LP) labeled in various positions. Accumulation of glycosaminoglycanes (GAG) in the time course of the atherosclerotic process was shown to be the factor contributing to the retention of LP in the vessel wall. At the same time, no GAG accumulation was found in sites of the greatest permeability. Irrespective of the stage of the process, formation of foci of increased permeability was, as a rule, associated with accumulation of poorly differentiated cells. The evidence of primary increase of permeability of the endothelial barrier in the form of activation of the proliferative processes and GAG accumulation was obtained.     

Histoautoradiographic study of the heart in experimental myocardial ischemia]

Autoradiographic examinations of the heart muscle in experimental myocardial necroses using 3H-thymidine, revealed a high DNA synthesis in the connective tissue cells in the zone of necrosis in the acute period of infarction and its subsequent decrease. Deviations from this regularity were observed when relapses of necrosis developed. The activation of DNA synthesis occurred to a lesser extent in stromal cells of the periinfarction and remote zones of the heart. Muscle cells incorporated 3H-thymidine extremely rarely. When myocardial infarction was combined with aterosclerosis, relapses of necrosis occurred frequently, and morphological changes in many arteries and veins were accompanied by 3H-thymidine incorporation into the nuclei of the endothelium, smooth cells and adventitial cells. Inhibition of DNA synthesis in connective tissue cells of various heart zones was observed in cases of combined myocardial infarction and aterosclerosis and hypertension.     

Histoautoradiographic characteristics of candidiasis pneumonia in combination drug therapy]

The lungs and organs of guinea pigs infected with fungus Candida against the background of cyclophosphamide immunodeficiency and therapy with antibiotics were studied morphologically. Secondary immunodeficiency and dysbacteriosis are shown to influence considerably the ability of fungal cells to utilize DNA and RNA precursors (tritium-labelled thymidine and uridine). Historadioautography allowed one to evaluate functional state of the infectious agent and host cell responses.     

Elevated atherogenic lipoproteins in childhood: Risk, prevention, and treatment

Elevated low-density lipoprotein cholesterol (LDL-C) level in childhood is an increasing problem, mainly due to a rising prevalence secondary to the childhood obesity epidemic and better recognition and screening. Vascular changes and impaired endothelial function associated with elevated LDL-C are apparent even in early childhood. Secondary adiposity-related cases are at higher risk due to the clustering of risk factors besides overweight, such as the atherogenic lipid triad, change in the atherogenic properties of the LDL-C particle itself, and the presence of insulin resistance. Prevention should focus on maintaining a healthy lifestyle, including a restricted fat and cholesterol diet, encouraging physical activity, and decreasing sedentary pursuits to maintain an appropriate weight in children. For children and adolescents found to have elevated LDL-C, management should focus on the pursuit of a healthy lifestyle mirroring that for prevention for at least 6 months. Additional dietary therapy, such as plant stanol and sterol esters, have also been shown to modestly reduce LDL-C levels. If the adoption of a healthy lifestyle is not sufficient to reduce LDL-C, lipid-lowering drugs should be considered in selected patients. Current drugs of choice are statins and potentially ezetimibe. Long-term treatment with statins has been shown to markedly reduce carotid intima-media thickness in children and adolescents, particularly when started early. Current evidence supports early and efficient treatment for affected children.     

Distribution of lipoproteins in the human aorta wall

Localization of lipoproteins of high, low and very low density in the wall of human aorta was studied by an indirect immunofluorescence technique using antibodies to apoproteins (apo) A-I, B-100 and C-III. Apo A-I and apo C-III were distributed relatively evenly through the thickness of the vessel without visible damage, with some prevalence in the zone of lipid infiltration. Apo B-100 were revealed in significant amount in the intima if their content in the aortic media was low. The content of apo A-I and apo C-III was somewhat increased in the lipid strip. Massive deposits of apo B-100 which were frequently distributed unevenly were found in the fibrous plaque. Pretreatment of nonfixed cryostat sections with saline solution containing bovine serum albumin produced a diffused decrease in the intensity of specific fluorescence this being due to the release of lipoproteins from the tissues. The mechanism of the low density proteins accumulation in the aorta, their binding to the vascular wall components is discussed.     

Character and mechanisms of changes in vascular wall reactivity in prolonged hypercholesterolemia]

Changes in the structure and functional properties of the vascular wall after 8 months of alimentary hypercholesterolemia (HCE) were studied. The experiments were conducted on the circular bands of the arch of the aorta in rabbits. Sharp inhibition of the reactivity of the vascular bands was established, which was associated first of all with thickening of the intima due to the development of fibro-atheromatous changes in it. At the same time, the smooth-muscle cells of the vascular wall maintained marked reactivity to various direct and receptor-mediated test effects. The functional significance of the endothelium in regulation of the vascular tonus, manifested by weakened endothelium-dependent relaxation, was sharply inhibited in the late stages of HCE. It is shown that reduction of the sensitivity of the smooth-muscle cells to the endothelium-dependent relaxation factor is the principal factor of weakening of the endothelium-dependent dilatational effects. After 8 months of HCE the aortic wall is capable of liberating a substance which is similar to the endothelium-dependent relaxation factor in its action, even when the thickened intima is completely removed.     

Histoautoradiographic study of [3H]thymidine uptake into parenchymal nuclei of the kidney and other organs in rats with nephrotoxic nephritis

Data were obtained to show how changes in the [³H]thymidine uptake by parenchymal nuclei of the kidney compare with those in other organs in rats with nephrotoxic nephritis. The labeling index in the kidneys increased: by 7.5 times in the epithelial cells of the renal cortex and by 15 times in the epithelium of the medulla. The number of labeled cells in the glomeruli increased by 2.5 times. The labeling index in the epithelium of the adrenals, liver, thymus, and small intestine fell to between 80 and 70% of normal.Central Scientific-Research Laboratory, Central Postgraduate Medical Institute, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 6, pp. 612–614, June, 1979.     

Effect of peptides of the tracheal mucosa and vascular wall in acute hyperoxic lung injury]

It was demonstrated that peptides of the tracheal mucosa (PTM) and peptides of the vascular wall (PVW) produce a certain protective effect in hyperoxic lung injury. The peptides, (PTM to a greater measure) prolonged the survival of mice and inhibited the dynamics of the growth of the lung coefficient in rats. PTM reduced the formation of malonic dialdehyde and increased the activity of glucose-6-phosphate dehydrogenase in the lungs. Morphometric studies showed that PTM produce a more marked inhibiting effect on exudation in to the alveoli; besides, the administration of PTM contributed greatly to maintenance of the empty space and "total volume" of the alveoli.     

胎儿耳蜗外侧壁微血管构筑的解剖学研究

目的 观察人类胎儿耳蜗外侧壁微血管形态、分布及生理学意义。方法 应用墨汁灌注和微血管铸型技术观察30例胎儿耳蜗外侧壁微血管形态。结果 耳蜗外侧壁由外放射状动脉供血,外放射状动脉走行于耳蜗前庭阶顶部,在耳蜗外侧壁形成四组毛细血管网,遍布耳蜗各回,分别为:血管纹血管网、前庭阶血管网、螺旋凸血管网和螺旋韧带深部血管网。耳蜗侧壁的静脉血流入鼓阶静脉。结论 26周龄以上胎儿耳蜗外侧壁微血管已发育完善,分布与其生理功能密切相关。     

Morphological and biochemical study of the lipid components of the fetal aorta]

We made a biochemical and histochemical study of the lipidic component of intima of fetal aortas on 8 autopsy cases (7 +/- 2 months aged) arrived at our observation in the Pathology's Institute of II Faculty of Naples. We made a study with freeze-sections stained with Oil-Red 0 and after dissociation of the intima by the adventitia, it is valued biochemically the lipidic peroxidation studying the levels of malonyldialdehyde (MDA) like indirect marker of peroxidation. It is known that is present a lipidic component in the intima of fetal aorta whether intracellular or extracellular (Fig. 1, 2). Sometimes this component can accumulate until to determinate true lipidic striae. The aim of this study is a detection of MDA in lipids extracted from human fetal aortas. MDA levels was measured by Thiobarbituric method (TBA): lipids were extracted both intima and adventitia by Chloroform/methanol method, after surgery immediately. The results are expressed in nMoles/mg of lipids +/- Standard Deviation. Controls of spontaneous lipid peroxidation was take at a different times. It is known that in vitro incubation of LDL with cultured endothelial cells, smooth muscle cells or macrophages leads to peroxidation of LDL phospholipids and oxidatively modified LDL become atherogenic via foam cells production. In addition lipid peroxidation was formed by the direct peroxidation of unsaturated fatty acids and their esters are capable of further lipoperoxide production by oxygen free radical; chain reactions. In this context lipid peroxidation could be an important factor in the first stage of human pathophysiological development and this phenomenon may be related by an early free radical production.     

Mechanism of self-maintenance of experimental atherogenic hyperlipoproteinemia]

Disorders of lipid catabolism in the liver and increased formation and intensified secretion into the blood of lipoproteins synthesized in the liver evidently play a significant role in the maintenance of experimental atherogenic hyperlipoproteinemia induced in rabbits by prolonged administration of atherogenic lipoproteins.