Biomedical subjects
Publications and source records attributed to M Winter.
In the presence of cimetidine, pentagastrin and somatostatin prostacyclin formation does not differ significantly from the value obtained with the buffer control, whereas cimetidine alone is able to inhibit ADP-induced platelet aggregation in vitro to a small degree. It is concluded that the in vivo action of the drugs if not primarily mediated by prostacyclin.
After oral and intravenous administration of drotaverin-14C its metabolites were determined in rat bile. Three major metabolites were identified by tlc. All the metabolites appeared in conjugated form. No unchanged drotaverine was detectable in the bile, except after treatment with doses much in excess of the therapeutic range. The ratio of major metabolites to unchanged product was determined by two-dimensional densitometry using a Telechrom Video Densitometer.
Unaltered human arterial tissue as well as different types of macroscopically and microscopically characterized atherosclerotic lesions were microdissected under a preparation microscope. The prostacyclin formation was examined using its potent platelet aggregation inhibition in vitro according to Moncada's bioassay. In contrast to different PGI2-formation in various experimental animal models the generation in the different lesion types in terms of wet weight was statistically significantly (p less than 0.001) diminished in comparison to normal control tissue. However, the PGI2- formation in different lesion types is comparable. Accepting the hypothesis delivered earlier by us, that the arterial wall is able to react upon exogenous noxes with a temporarily enhanced PGI2-formation, followed (after ceasing) by a decrease of PGI2-synthesis (exhaustion phenomenon) it can be concluded, that the critical stage is prior to the fatty streak formation, which is a preatherosclerotic lesion. Therefore, PGI2-generation-exhaustion might be mainly responsible for initiation and progression of atherosclerosis, probably before any detectable morphological alterations.
A tube leucocyte adherence test was used to detect reactivity of melanoma patients to extracts of melanoma tissue. Breast cancer extracts were used as a control. Of 31 melanoma patients 22 gave a positive reaction (non-adherence index > 25%) to melanoma extracts whereas only three of 24 normal subjects did so. Fifteen of 16 patients with Stage 1 melanoma reacted but only seven of 15 patients with Stage 2 or Stage 3 disease did so. None of seven patients with breast cancer reacted to melanoma extract, but four of them reacted to breast cancer extract. None of four patients with benign breast disease reacted to either extract. It is concluded that leucocyte adherence inhibition is potentially useful in investigations of tumour-specific immune reactivity to melanoma and of melanoma antigens.
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In the early phase of malignant renal hypertension induced by aortic ligature, a transient activation of transmural aortic permeability is observed. The transmural permeability shows its maximum during the first week of hypertension returning in the third week to normal or even subnormal values, whereas the blood pressure is still rising. The permeability disturbance precedes the structural transformation of the arterial wall. Although the aortic segments above and below the ligature are exposed to different blood pressure and hemodynamic stresses their patterns of permeability disturbance are the same. If the kidney below the aortic ligature is removed no permeability disturbance can be observed. Aortic wall PGI2-formation both above and below the ligature is elevated in the first phase of hypertension. The PGI2-synthesis returns to normal values during the 5th week. Our data suggest that in the early phase of renovascular hypertension there is an increased aortic antiaggregatory activity and that PGI2 is probably not the compound responsible for increased transmural permeability. Moreover, the blood pressure and the hemodynamic forces have no decisive importance in the induction of the aortic transmural permeability disturbance.
In 38 preoperative patients the production of urea was estimated and the cell-mediated immunity was measured. 10 patients were catabolic and had negative skin tests, all of them were inoperable. 15 patients were catabolic and had positive skin tests five patients were inoperable. 12 patients were not catabolic and had positive skin tests, two were inoperable. One female patient was not catabolic and had negative skin tests, but was operable. The catabolic state can be assessed by the urea production rate and you can give prognostic and therapeutical references in correlation with the delayed hypersensitivity.
In 38 preoperative patients the production of urea was estimated and cell-mediated immunity was measured. Ten patients were catabolic and had negative skin tests, all of them were inoperable. Fifteen patients were catabolic and had positive skin tests, five patients were inoperable. Twelve patients were not catabolic and had positive skin tests, two were inoperable. One female patient was not catabolic and had negative skin tests, but was operable. The catabolic state can be assessed by the urea production rate and one can give prognostic and trophotherapeutical indications in correlation with the degree of cellular immunity.
The human gastric mucosa generates prostacyclin (22 +/- 6 ng PG I2/g). There is no age or sex difference in PG I2 formation by normal gastric mucosa. The properties of the substance are the same as reported in other tissues.
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The newly formed tissue of dacron vascular prosthetic grafts implanted in humans demonstrates prostacyclin generation and fibrinolytic activity comparable to that of the atherosclerotic artery in the vicinity. This provides some evidence that both activities important for haemostasis run parallel.
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The absorption and biliary excretion of drotaverin/a papaverine analogue/were studied in rats. In vivo loop technique was used. The absorption of the compounds from the jejunum was found to be rapid and the activity injected into the duodenal sac to disappear only when the common bile duct was ligated. An appreciable activity was detected in the bile collected by cannulation following both i.v. (67%) or per os (31%) administration. Considerable activity was excreted with the bile even 24 hours after drug administration. A partial entero-hepatic cycle for the drotaverin metabolites is suggested.
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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.
Quantitative changes in the internal elastic membrane (IEM) were studied in human arteries from different location in 31 males and 31 females, using an eight-criterion classification system. The IEM involvement shows a sex-dependent increase with age, and is more pronounced in arteries known to exhibit a more intensive atherosclerotic involvement. It seems that the IEM changes represent a true ageing phenomenon, which is sometimes influenced to a various degree by the atherosclerotic process.
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.