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Biomedical subjects

H Sinzinger

Publications and source records attributed to H Sinzinger.

At least 361 records · Page 20Linked to original sources
PubMed1987

A new medium improves sampling for determination of platelet factor 4 in human plasma.

The determination of alpha-granule specific platelet proteins in human plasma is a valuable indicator of in-vivo release and platelet activation provided that an artificial in-vitro release during sampling can be avoided. A new sampling medium (M) has been compared with the commercially available ones for the sampling and the subsequent determination of platelet factor 4 and beta-thromboglobulin. M allows blood withdrawal at room temperature (22 degrees C) (3.49 +/- 0.7 ng/ml) without any difference to 4 degrees C (3.47 ng/ml) up to a 30 minutes sedimentation period. However, after 40 minutes there is a significant (p less than 0.01) increase, amounting at 22 degrees C (13.30 ng/ml) and at 4 degrees C 6.68 ng/ml. The addition of prostacyclin (PGI2) in-vitro as well as blood withdrawal from volunteers infused with PGI2 at a rate of 5 ng/kg/min did not alter the values of M-preserved samples, whereas in the commercially available ones, PGI2 caused a decrease. A comparison of radioimmunoassay and enzyme immunoassay exhibited no significant difference in the absolute values. Beta-thromboglobulin was assayed as control. The findings indicate M being optimal for the sampling of platelet factor 4, but not for other alpha-granule release products. Thus, there is again evidence, that the alpha-granule products are not released to an equal extent upon a certain stimulus. Furthermore, it seems likely, that various substances inhibit their liberation from the platelet to a differing extent.

Adult↗
PubMed1987

[Modification of eicosanoid synthesis by calcium dobesilate].

Calcium dobesilate is a vasoactive drug with well-known effects on endothelial integrity, vascular wall permeability and blood viscosity. A clinical study demonstrated that serum thromboxane formation is significantly decreased by calcium dobesilate in patients suffering from peripheral vascular disease. Hence an in vitro study has been undertaken to determine the influence of calcium dobesilate on eicosanoid formation both by platelets and the arterial wall. Radio-thin-layer chromatography (RTLC) of human platelets does not show any influence of the drug on eicosanoid conversion in a dose range from 10 to 1000 micrograms/ml. By contrast, the vascular conversion of eicosanoids shows a dose-dependent trend towards a decrease in cyclooxygenase products. However, using the same doses, no effect is observed on vascular PGI2 formation in vitro, as assessed by means of the platelet aggregation bioassay and thus no inhibitory effect on cyclooxygenase of the arterial wall can be deduced. These laboratory findings provide no explanation for the clinical efficacy of calcium dobesilate and the diminution in serum thromboxane. A different mode of metabolic conversion of endogenous and exogenous arachidonic acid is suggested as explanation for these contradictory results.

Arachidonic Acid↗
PubMed1987

Interferon-alfa corrects thrombocytosis in patients with myeloproliferative disorders.

During previous therapeutic trials with interferon, decreased levels of peripheral platelet counts have been observed. Taking advantage of this effect, we investigated the efficacy of recombinant interferon (rec-IFN) in the treatment of thrombocytosis in myeloproliferative diseases. A total of 15 patients with polycythemia vera, essential thrombocytosis, or chronic myeloid leukemia received rec-IFN-alfa at initial doses of 25-70 x 10(6) units/week; maintenance therapy following week 8 of treatment consisted of 20-35 x 10(6) units/week rec-IFN. Observation periods ranged from 24 to 48 weeks. Significant reductions in the number of platelets were noted in all cases; 12/15 patients achieved platelet counts below 440 x 10(9)/l and maintained those normal values for at least 4 weeks. The number of bone marrow megakaryocytes, which had been increased prior to treatment, diminished during rec-IFN therapy, while the previously shortened platelet half-life further decreased with rec-IFN treatment. During rec-IFN-induced remission, the plasma levels of platelet factors, the activity of natural killer cells, and platelet aggregation showed changes between slight improvement and normal values. Severe side effects were only observed with the highest rec-IFN doses; dosage adjustments were effective in improving or eliminating all treatment-related symptoms. Rec-IFN may prove to be a valuable therapeutic alternative to cytostatic treatment of thrombocytosis in myeloproliferative disorders.

Aged↗
PubMed1987

Prostaglandin I2 during radiolabelling improves recovery, but does not change platelet half-life and platelet uptake over active human lesion sites.

The fact that prostacyclin is able to preserve platelets in-vitro stimulated the question whether platelets being treated in presence of prostacyclin might behave different after reinjection in human. We therefore studied the effect of synthetic PG12 in-vitro, being added immediately after blood sampling. It is demonstrated that the presence of prostacyclin does not change the labelling efficiency and in-vitro viability beside the alterations induced by this compound itself, however, it results in a significantly improved recovery. Furthermore, the platelet half-life in the patients as well as the deposition of the radiolabelled platelets on active human atherosclerotic lesions does not seem to be affected. Thus, the addition of PGI2-improves cellular viability during the preparation without negatively interfering with the in-vitro and in-vivo results later on. Thus, the use of PGI2 can be strongly recommended.

Aged↗
PubMed1987

Prostaglandin I2 reduces activation of human arterial smooth muscle cells in-vivo.

Patients suffering from peripheral vascular disease have been "ultima ratio"-treated with PGI2 at a rate of 5 ng/kg/min for 6 hours a day and 5 consecutive days i.v. 20 of them underwent surgery thereafter as therapy was not sufficient. A histological examination and quantification of vascular tissue revealed that the number of activated smooth muscle cells was significantly lower in treated patients vascular segments than in untreated ones in all the different age groups. A comparable suppression was found in the intima and the media as well. It is thus concluded, that PGI2 inhibits smooth muscle cell proliferation most probably by inhibiting PDGF-release from the platelets and stimulation of smooth muscle cell cAMP. To achieve a more beneficial PGI2-effect at the vascular level, a prolonged PGI2-therapy looks rather promising.

Arteries↗
PubMed1987

Platelet function and prostaglandins in patients with peripheral vascular disease treated with calcium dobesilate.

In a double-blind placebo controlled study, 25 male patients (age range: 48-67 years) suffering from peripheral vascular disease were treated daily for 4 weeks with either 2 g of calcium dobesilate (n = 13) or placebo (n = 12). Different platelet and prostaglandin parameters were examined before and at the end of therapy. The number of circulating endothelial cells decreased significantly (4.9 +/- 2.9 to 2.0 +/- 1.9; p less than 0.0004). In addition, a decrease in serum TXB2 was noted (p less than 0.0001), but no significant change in plasma TXB2. The fibrinogen half-life was shortened (p less than 0.0001) and the platelet half-life was prolonged (p less than 0.04). The level of beta TG was decreased (p less than 0.006), but PF4 was unchanged. No alteration in the conversion of exogenous 14C-arachidonic acid by platelets to eicosanoids was observed. These observations indicate that calcium dobesilate is able to exert a favourable effect on some parameters of platelet function and prostaglandin synthesis which are important in the regulation of the hemostatic process. It is suggested that these pharmacological actions might explain, at least in part, the beneficial clinical effect of the drug.

Aged↗
PubMed1987

Prostacyclin synthesis stimulating plasma factor in patients with peripheral vascular disease.

Human plasma contains a factor capable of stimulating vascular prostacyclin generation even in atherosclerotic vessels with minimal in-vitro capacity for PGI2-synthesis. The activity of this prostacyclin stimulating plasma factor (PSPF) has been reported to be elevated in renal failure and hepatic coma. We are not aware of any data as to whether this PSPF plays a role in maintaining hemostatic balance in patients with peripheral vascular lesions. Therefore, we examined 62 patients with peripheral vascular disease (PVD). This study group was subdivided into normo- and hyperlipemic subjects, patients with and without maturity onset diabetes, and plasma beta-thromboglobulin levels higher and lower than 50 ng/ml. 10 healthy sex and age matched persons served as controls. Vascular prostacyclin formation was studied in vitro after incubation of the patients' plasma and a buffer control with various tissue samples (human femoral artery, rat abdominal and thoracic aorta of healthy and of streptozotocin induced diabetic animals, swine endothelial layer and remaining tissue (media and adventitia) and cultured endothelial (EC) and smooth muscle cells (SMC) of minipig arota. In addition, 6-oxo-PFG1 alpha formation by cultured EC and SMC (minipig aorta source) after incubation with tris HCl-buffer or plasma were estimated by means of specific radioimmunoassays. In general, tissue samples and cells incubated in plasma exhibit a marked increase of in-vitro PGI2-formation as compared to buffer. No difference could be found between PSPF of CHD-patients and healthy controls. Similar findings were obtained using incubated vascular tissue and cultured cells by means of the bioassay and specific RIA, respectively. These findings indicate that the PSPF does not seem to be of any clinical relevance in hemostatic regulation in patients with advanced atherosclerosis.

Adult↗
PubMed1987

Development of optimal infusion regimens for epoprostenol using radio labelled platelet uptake over atherosclerotic lesions in man.

1. Epoprostenol (prostacyclin, PGI2) has been evaluated in clinical trials in peripheral vascular disease and other conditions chiefly on the basis of its platelet inhibitory properties. These therapeutic evaluations have proceeded in the absence of evidence as to the optimum infusion regimen for epoprostenol and the choice of schedules of administration has been arbitrary. We have tried to establish an optimum infusion regimen in patients with peripheral vascular disease in terms of maximal inhibition of platelet deposition on atherosclerotic lesions in vivo together with maximal inhibition of platelet aggregation ex vivo. 2. One hundred and twenty three patients with atherosclerotic peripheral vascular disease and increased platelet uptake at atherosclerotic sites were selected. Epoprostenol was administered at a fixed dose of 5 mg kg-1 min-1 for 0.5-24 h daily for 3-7 days. 3. Infusion of epoprostenol for 6 h daily for up to 5 days caused maximum decrease in platelet uptake without tachyphylaxis and without loss of the inhibitory effect of epoprostenol on platelet aggregation responses. Longer daily infusion periods were associated with progressive loss of the anti-aggregatory effect of epoprostenol without any greater decrease in platelet uptake. Shorter daily infusion periods produced smaller decreases in platelet uptake.

Adenosine Diphosphate↗
PubMed1987

Effect of prostaglandin E1 on deposition of autologous labelled platelets onto human atherosclerotic lesions in vivo.

The effects of infusions of prostaglandin E1 (PGE1) on platelet deposition at atherosclerotic sites in vivo in man have been examined. Thirteen patients with atherosclerotic vascular disease received intravenous PGE1 25 mg/kg/min for 6 hours daily for 5 days. Prostaglandin E1 had no effect on platelet uptake at atherosclerotic sites but prolonged platelet half-life significantly (P less than 0.001).

Alprostadil↗
PubMed1987

Eicosanoids of platelets and vascular wall in chronic renal insufficiency.

There is good evidence that retention products accumulating in chronic renal insufficiency influence prostaglandin (PG) synthesis, thus affecting platelet-vascular wall interaction. The vascular PGI2 synthesis is increased and prolonged in vitro, the plasma factor activity enhanced. A defective platelet function is frequently observed; it is completely restored by peritoneal dialysis, but only partially by hemodialysis. The sensitivity of platelets to PGI2 and its plasmatic degradation are unchanged. There is evidence of a shift of arachidonic acid metabolism from cyclooxygenase to lipoxygenase. These changes may be attributed to undialyzable plasma constituents, the 'middle molecules'.

Arachidonic Acids↗