Ultrastructural informational analysis of the dynamics of liver cell recovery after performance of a biliodigestive anastomosis in mechanical jaundice]

Hepatic ultrastructure has been studied in dogs at the level of cholestasis and at different time after cholecystenteroanastomosis. Owing to theoretico-informative approach applied in the investigation, it was possible to reveal certain essential disorganization in hepatic ultrastructures on the 7th day after the operation. This phenomenon seems to explain the occurrence of acute hepatic insufficiency at early postoperative stages not infrequently observed in clinic. Changes produced by 30-days' cholestasis are demonstrated to be reversible.     

Ultrastructural bases of the development of the neural apparatus of the heart

By means of electron microscopy developmental dynamics of the human and mammalian innervation has been studied during prenatal period of ontogenesis. Regularities in formation of the intracardiac nervous ganglia and in differentiation of nervous-muscular connections in the myocardium have been stated. Ultrastructural peculiarities of proneuroblasts and the nervous fiber terminals, growing to differentiating cardiomyocytes have been described during the premediator stage of the vegetative nervous system development. Peculiarities of synaptogenesis have been followed, among them those demonstrated as heterochromic formation of pre- and post-synaptic membrane and as uneven accumulation of synaptic vesicles. Development of the nervous-muscular connections have been studied. At the beginning of the mediator stage of the vegetative nervous system development formation of simple contacts between the nervous terminals and cardiomyocytes is intensified, and glial tunics develop rather poorly. Therefore, at the beginning the terminal parts of axons are not surrounded with processes of gliocytes. Simultaneously, formation of small intensively luminescent cells takes place. Development of afferent nervous terminals occurs not only in the myocardium, but in the intracardiac ganglia.     

Cytokine characteristics of jaundice in mouse liver

OBJECTIVE: The aim of this study is to clarify the perioperative cytokine changes and their mechanism in jaundiced liver. MATERIALS AND METHODS: Obstructive jaundice was induced using a common bile duct ligation (CBDL) and a two-thirds hepatectomy (HEP) was performed in six- to seven-week-old male C3H/HeN mice. When hepatectomy was added to CBDL, it was carried out 2 to 5 days after CBDL. The serum interleukin 6 (IL-6) levels and heat shock protein (HSP)-70 expression were evaluated. One mg per mouse of methylprednisolone (MPL) was intraperitonealy administered in some mice of CBDL+HEP group. RESULTS: The post-hepatectomy IL-6 values at 2 and 3 days after CBDL were significantly lower than those in the HEP group, while those at 5 days after CBDL were significantly higher than those in HEP group. The serum IL-6 value of the steroid group was significantly lower than that of non-steroid group in HEP group. However, no steroid effects were recognized on post-hepatectomy IL-6 values at 3 days after CBDL, steroid inhibited post-hepatectomy IL-6 production at 5 days after CBDL. No expression of HSP70 protein was observed in the control group, but HSP70 protein was expressed in both the hepatocytes and Kupffer cells 3 days after CBDL, then at 5 days after CBDL, no HSP70 protein was expressed in the Kupffer cells. CONCLUSIONS: In the early period of obstructive jaundice, the IL-6 level after hepatectomy did not increase in comparison to HEP group, and steroid had no effect on IL-6 level. According to the progression of obstructive jaundice, the IL-6 level after hepatectomy increased to a higher level than before, and the effect of MPL was restored. HSP70 is thus suggested to have an important role in cytokine production.     

Therapeutic effect of the transfusion of UV-irradiated donor plasma in mechanical jaundice

The method of intravenous administration of UV-irradiated donor plasma to patients with jaundice of different genesis has been tested in the experiments on rats and used clinically in 20 patients. Biochemical and morphological studies have shown that such treatment causes stable improvement in the liver functional state.     

Ultrastructural detection of cholesterol in the liver in chronic alcoholic intoxication

The authors studied the deposits of cholesterol in the liver of alcoholic men and rats by means of cytochemical method. The localization of cholesterol in intracellular and extracellular compartments was shown. In numerous hepatocytes there were focal destructions in mitochondria, rough endoplasmic reticulum and plasma membranes.     

Ultrastructural investigations on the question of mechanical activation of blood platelets

The present study addresses the question whether platelets are activated by mechanical stresses as they occur in pathologically accelerated blood flow. Their potential mechanoreceptive properties were tested by subjecting human platelets to defined fluid mechanical forces for periods of milliseconds. Platelet activation was assessed by quantitative morphology, revealing besides activated platelets, irreversibly ballooned, lytic platelets. However, this morphometrically documented "shear activation" of platelets can be suppressed almost completely by the addition of enzyme-substrate systems, capable of removing adenosine diphosphate from the suspending medium. This is in keeping with a recent study from our laboratory showing that the behaviour of lactic dehydrogenase as marker for platelet lysis and beta-thromboglobulin as release marker refuted earlier data, suggesting a direct activation of platelets by shear. It is concluded that former evidence of "shear induced platelet activation" must be interpreted as the consequence of lytic damage to a small proportion of platelets.     

Molecular and mechanical bases of focal lipid accumulation in arterial wall

Mechanical forces such as shear stress can modulate gene and protein expressions and hence cellular functions by activating membrane sensors and intracellular signaling. Using cultured endothelial cells, we have shown that laminar shear stress causes a transient increase in monocyte chemotactic protein-1 (MCP-1) expression, which involves the Ras-MAP kinase signaling pathway. We have demonstrated that integrins and the vascular endothelial growth factor receptor Flk-1 can sense shear stress, with integrins being upstream to Flk-1. Other possible membrane components involved in the sensing of shear stress include G-protein coupled receptors, intercellular junction proteins, membrane glycocalyx, and the lipid bilayer. Mechano-transduction involves the participation of a multitude of sensors, signaling molecules, and genes. Microarray analysis has demonstrated that shear stress can upregulate and downregulate different genes. Sustained shear stress downregulates atherogenic genes (e.g., MCP-1 and the genes that facilitate lipid accumulation) and upregulates growth-arrest genes. In contrast, disturbed flow observed at branch points and simulated in step-flow channels causes sustained activation of MCP-1 and the genes facilitating cell turnover and lipid accumulation. These findings provide a molecular basis for the explanation of the preferential localization of atherosclerotic lesions at regions of disturbed flow, such as the arterial branch points. The combination of mechanics and biology (from molecules-cells to organs-systems) can help to elucidate the physiological processes of mechano-chemical transduction and improving the methods of the management of important clinical conditions such as coronary artery disease.     

Ultrastructural aspects of the reversible nature of sclerotic changes in the liver

Experiments on mice have demonstrated ultrastructural changes in collagen and hepatocytes during reverse development of liver cirrhosis. Progressive lysis of collagenous fibers has been noted. Changes in hepatocytes point to a rise in the synthetic and endocytosis activity in these cells. It is suggested that exocellular lysis of collagen in the process under consideration is initiated by collagenase whereas subsequently it takes place under the action of lysosomal enzymes secreted by hepatocytes to the exocellular space.