Decreased vascular prostacyclin in juvenile-onset diabetes.
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Biomedical subjects
Publications and source records attributed to K Silberbauer.
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Activated smooth muscle cells exhibit a statistically significant (p less than 0.025) higher prostacyclin production than the contractiles. It is concluded, that the proliferation of the metabolically activated cells, which is an early event in atherogenesis, could be due to prostacyclin regulation.
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Plasma beta-thromboglobulin levels were determined in 22 multiple myeloma patients, in 15 patients with polycythaemia vera and in 70 healthy controls. In both multiple myeloma and polycythaemia vera significantly increased plasma concentrations of this platelet-specific protein were found.
Subendothelium of blood vessel segments from elderly patients was exposed in a perfusion chamber to citrated blood under arterial blood flow conditions. The resulting platelet adhesion and thrombus formation was assessed morphometrically. The results show that the time course and the extent of platelet adhesion and aggregation were similar to the results obtained previously with subendothelium from rabbit arteries. The extent of surface-induced platelet aggregation was furthermore governed by both the properties of the exposed surface as well as those of the blood perfusate. No significant differences with regard to platelet reactivity were found between veins and arteries and the extent of surface-induced platelet aggregation was rather low.
1. PGI2 is synthetized in human gastrointestinal mucosa. 2. PGI2 seems to be responsible for pathophysiological conditions. 3. Disorders caused by an enhanced or diminished PGI2-synthesis could be treated in the future by inhibition of prostacyclin synthetase or exogenous synthetic PGI2 respectively. 4. In order to remove the problems with the unstable PGI2, synthetic analogs could be used for the treatment.
Prostacyclin (PGx, PG12) activity can be found in renal tissue as indicated by platelet aggregation inhibition. The activity of the medullary tissue in terms of wet weight is significantly higher (P less than 0.01) than that of cortex. The activity decreases with time and has almost entirely gone within 1 h. Boiling for 30 s destroys the inhibitory effect of the prostacyclin on platelet aggregation. Angiotensin II is able to stimulate the prostacyclin availability of the tissue after incubation for 3 min. Addition of angiotensin II to platelet-rich plasma (PRP) has no significant effect on ADP-induced platelet aggregation. The spontaneous generation of prostacyclin as well as that stimulated by angiotensin II can be suppressed by previous incubation of the tissue with a prostaglandin synthetase inhibitor such as ketoprofen. Tissues which have only a small amount of basal release in buffer show an increased platelet aggregation inhibitory effect after addition to PRP. The difference between medulla and cortex is statistically significant. This different release of prostacyclin cannot be related to different endothelial surface area, because the endothelial surface in medulla and cortex is quite similar. It is suggested that prostacyclin has an important influence on the renal function. The different capacity of renal medulla and cortex in generation of prostacyclin could be of great importance for a fuller understanding of the physiology of renal function.
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After inhalation of prostaglandin I2 minimal effects on lung function and the cardiovascular system could be observed in healthy volunteers. Platelet function, however, decreased significantly. In the future the application of the prostaglandin I2 may be a new approach in the treatment of thromboembolic disorders in man.
Various sorbents were tested in-vitro for their ability to support hepatic excretory and detoxification functions, and their in-vivo perfusion with plasma was studied in an animal experiment. Amino acids, particularly phenylalanine and tyrosine, were strongest bound by activated charcoal, while Amberlite XAD-7 removed conjugated and unconjugated bilirubin and bile acids from plasma. Using a cell-separator plasma of dogs, in whom acute liver failure was induced by yellow phosphorus, was perfused through a combination of charcoal and Amberlite XAD-7 without major complications. Platelet counts remained nearly unchanged, platelet aggregation was inhibited reversibly, and circulating platelet aggregates occurred late only. It is concluded that using the method described, therapeutic trials in patients with fulminant hepatic failure can be performed.
Recently new radioimmunoassay methods have been established to measure plasma concentrations of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4), platelet release products which are set free when platelets aggregate. Plasma concentrations of beta-TG and PF4 were investigated in disorders with increased thromboembolic risk. Extremely high concentrations of these platelet proteins were found in patients with venous thrombosis, pulmonary embolism, polycythemia vera, and chronic renal failure. Moderately increased beta-TG and PF4 levels were observed in patients with peripheral vascular disease, coronary artery disease, chronic rheumatoid arthritis, multiple myeloma, and diabetes mellitus. These data indicate, that plasma concentrations of beta-TG and PF4 are useful parameters for the evaluation of the "in vivo" platelet activity. By using these new methods for clinical applications special blood sampling conditions have been taken into account; moreover one has to consider that the plasma levels of the platelet "release products" are dependent from renal function.
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Morphological control of Moncada's bioassay for prostacyclin (PG I2) activity measurement shows that the activity depends not only on endothelium, but in important amounts on subendothelial tissue too. Therefore, it can be concluded that platelet thrombus formation after endothelial cell injury does not depend only on the PG I2-producing ability of the tissue.
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