Search PubMed⌕ Search

Biomedical subjects

H Sinzinger

Publications and source records attributed to H Sinzinger.

At least 181 records · Page 10Linked to original sources
PubMed1995

[Thrombocyte function of healthy probands taking 50 mg of acetylsalicylic acid per day].

The antithrombotic effect of acetylsalicylic acid (ASS) is attributed in part to its inhibitory action on platelet cyclooxygenase and, thereby, thromboxane A2 (TXA2) formation. The therapeutic goal of low-dose ASS regimens was the development of a preparation showing a high inhibitory capacity on platelet TXA2 generation whilst leaving vascular prostaglandin I2 (PGI2) synthesis unaffected, thereby minimizing side effects. The effect of a new acid-resistant preparation of 50 mg ASS (Thrombo-ASS 50 mg) on plasma levels of ASS, salicylate, TXB2, 11-dehydro-thromboxane B2, serum thromboxane B2 and malonyl dialdehyde, the conversion of exogenous 14C-arachidonic acid to TXB2 and hydroxy-5,8,10-heptadecatrienoic acid (HHT), as well as on the urinary metabolites 2,3-dinor-6-oxo-PGF1 alpha and 2,3-dinor TXB2, were compared in a crossover trial to those of a marketed preparation (Aspirin 100 mg) in healthy volunteers after a single dose and repeated administration of ASS. While platelet activity was inhibited by both the test and the reference substance to a comparable extent, vascular PGI2 production (as determined by urinary 2,3-dinor-6-oxo-PGF1 alpha excretion) was less affected by the test substance. These findings confirm the claim that a dosage of 50 mg ASS administered daily as an enteric coated or uncoated tablet is sufficient to almost completely block platelet cyclooxygenase, while the respective vascular enzyme is only minimally affected.

Adult↗
PubMed1995

[Stimulation of platelet mitogen-induced prostaglandin I2 synthesis in periodontal tissue of cyclosporin A treated patients].

Cyclosporine A (CsA) is a highly potent immunosuppressive agent that has proven to be particularly useful in organ transplantation. Like phenytoin and the calcium antagonists, this drug may be associated with gingival hyperplasia. This study examined the interaction of platelet derived growth factor (PDGF) with prostaglandin I2 (PGI2)--a potent mediator in inflammation and bone resorption. PGI2 synthesis was examined by bioassay in gingival tissue from rats, rabbits and humans. Gingival tissue from CsA-treated patients generates less PGI2. PDGF causes a dose-dependent increase in PGI2 release in both CsA-treated and control subjects. The actual and percentage increase in PGI2 synthesis, however, was significantly higher in control tissue. While PDGF on the other hand modulated cellular proliferation, it causes on the other hand liberation of PGI2 from gingival tissue, thus interfering with its own action and further synthesis. If the PGI2 response is insufficient as after CsA therapy, the proliferative action might dominate. These findings therefore suggest an important pathogenetic role of PDGF and possibly other growth factors in CsA-induced gingival hyperplasia. "CsA gingivitis" seems to be a predominantly proliferative process, whereby inflammatory reactions appear only as a secondary phenomenon.

Adult↗
PubMed1995

PGE0 inhibits collagen and glycosaminoglycan-synthesis in the rabbit arterial wall.

The influence of 13,14-dihydro-PGE1 (PGE0), a biologically active metabolite of PGE1, on collagen and glycosaminoglycan synthesis by the rabbit arterial wall was assessed and compared with the effect of PGE1. Collagen (COL) and glycosaminoglycan (GAG) synthesis was measured using 14C proline- and 35S-incorporation respectively and both were subsequently quantified by autoradiography. PGE1 decreased GAG-synthesis by 40%, while PGE0 caused a 25% decrease. COL-synthesis after PGE1 treatment was diminished by 35%, while the biologically active metabolite caused a drop of 30%. Five and 15 micrograms/kg doses of both compounds were almost equally effective, 1 microgram was without effect. These findings indicate that PGE0 shares the inhibitory effect of PGE1 on COL and GAG biosynthesis. This metabolite has about 60 to 70% of the biological activity of its parent compound PGE1. These results suggest that part of the effects of PGE1 in inhibiting extracellular matrix production could be due to its metabolite PGE0.

Alprostadil↗
PubMed1995

Radiation-induced vascular damage.

A 55-year-old male underwent detailed angiological and biochemical investigation because his daughter suffered from myocardial infarction in the 29th gestational week. An inborn familial plasma factor defect and increased Lp(a) were detected. Localized vascular changes were found in the right femoral artery while the resting vascular system was normal. Anamnestic data revealed a testicular cancer and therapeutic irradiation in that area (5000 rad) 12 years ago.

Biological Factors↗
PubMed1995

The effect of NO/EDRF and monocytes/macrophages on LDL-oxidation.

Beside prostaglandin (PG) I2 and tissue plasminogen activator (tPA), nitric oxide (NO) is a key fepellant substance contributing to haemostatic balancing. The role of low-density lipoproteins (LDL) in the pathogenesis of atherosclerosis has been gaining increasing importance. It is well accepted that LDL in their modified (i.e. oxidized) form are no longer recognized by the LDL-receptor, but are taken up by cells of the arterial wall, especially macrophages, in a non-regulated manner through the so called scavenger-receptor pathway. This process leads to the formation of foam cells, the hallmark of the atherosclerotic lesion. NO is also produced in relevant amounts by macrophages. The interaction of NO and LDL with macrophages is thus of key importance in the onset of early lesions. While oxidized LDL (oxLDL) are resulting in a decreased NO availability, NO seems to prevent LDL-oxidation. In contrast, however, in the presence of superoxides oxidation may result. All these potential actions have to be discussed in view of the extremely short half-life of NO indicating that these actions are restricted most likely to the local site of biosynthesis being dependent on the actual concentration, the duration of availability and the presence of transition metals. These findings indicate that NO may play a dual pro- and antiatherosclerotic role being dependent on local factors only.

Animals↗
PubMed1994

Isradipine decreases arterial thrombogenicity in rabbits. A morphometric and radioisotopic study.

The effect of isradipine, a calcium antagonist, on aortic and iliac wall thrombogenicity was examined in rabbits. After one week of dosing, the abdominal aortic and iliac artery endothelium was abraded using a Fogarthy catheter. One group of animals (n = 8) was dosed for one week with isradipine 0.3 mg/kg. A second group of animals received 10 mg acetylsalicylic acid (ASA)/kg daily in addition, while a third group received the vehicle only. Finally, a fourth group of animals (n = 8) was treated with ASA only. The percentage denuded surface covered with contact (unspread) platelets decreased significantly (p < 0.01) from 14.7 +/- 2.0 to 9.3 +/- 2.1 (6.2 +/- 0.8 to 3.7 +/- 0.4). The amount of contact and spread platelets was diminished from 84.9 +/- 5.6 to 71.4 +/- 4.4 (91.8 +/- 5.3 to 75.2 +/- 4.6). Platelet thrombi decreased from 7.4 +/- 0.9 to 4.6 +/- 1.4 (9.4 +/- 1.9 to 5.2 +/- 0.7) in the aortic and the iliac artery, respectively. In-platelet deposition decreased by 39.9 and 41.9%. Concomitant ASA therapy not only abolished the effect of isradipine but enhanced thrombogenicity, probably as a result of almost complete blockade of vascular PGI2-production.

Animals↗
PubMed1994

Isradipine inhibits mitotic and proliferative activity in the arterial wall.

The anti-mitotic (3H-thymidine uptake quantified using autoradiography) and anti-proliferative (counting of activated smooth muscle cells on semithin sections) effects of the dihydropyridine calcium channel blocker isradipine (0.3 mg/kg) have been assessed in a rabbit arterial stress model. Isradipine caused a significant drop in both mitotic and proliferative activity. These effects were more pronounced by pretreatment (6 hours before lesion induction with desoxycorticosterone) with isradipine as compared to posttreatment (6 hours after experimental lesioning). The benefit induced by isradipine was abolished by aspirin treatment. In-vitro vascular prostacyclin formation and cholesterol content were not affected. These findings suggest that the anti-atherosclerotic action of isradipine on mitotic activity and cellular proliferation is mediated by a cyclooxygenase product, most likely via enhanced local vascular PGI2-synthesis.

Animals↗
PubMed1994

Synergistic antiplatelet action of nitric oxide (NO) with PGD2 and its metabolite PGJ2--relevance for cerebral circulation?

The PGI2/NO axis is well accepted for its central regulatory role in maintaining haemostatic balance in large arteries. Earlier findings suggest that PGD2 may also play a role in haemostatic regulation of human cerebral circulation. We therefore wondered whether PGD2 and its metabolite PGJ2 synergise in-vitro with NO. We approached this question using platelets of ten healthy donors and ADP as aggregation-inducing stimulus. Both PGD2 and PGJ2 do inhibit ADP-induced platelet aggregation in a dose-dependent manner. Platelet aggregation findings demonstrate that PGD2 and NO synergise, as does the metabolite PGJ2. Our data are indicative that the PGD2/NO and, in less extent, PGJ2/NO synergism might be of special importance for the cerebrovascular haemostatic control.

Adenosine Diphosphate↗
PubMed1994

Lipoprotein (a) in peripheral arterial occlusive disease.

Recent studies have shown high levels of lipoprotein (a),--Lp(a)-, an atherogenic and thrombogenic lipoprotein, are considered a risk factor for coronary heart disease. This study evaluated Lp(a) levels, as well as other lipid factors, in a group of 45 patients affected by stage II peripheral arterial occlusive disease (PAOD). An age-, sex- and Body Mass Index-matched group of healthy controls was also recruited. Exclusion criteria were diseases or drugs which could alter Lp(a) levels. Alterations in lipid profiles, which are often associated with PAOD, were observed in the patients. Lp(a) levels did not differ significantly in the two groups (median 16.4 mg/dl, range 10-104, in PAOD and 9.9 mg/dl, range 7.4-66.7, in controls and means 21.7 +/- 17.5 mg/dl and 21.2 +/- 16.8 mg/dl respectively) but in 51% of the controls Lp(a) levels were < 10 mg/dl compared with 20% of the PAOD patients (p < 0.05).

Aged↗
PubMed1994

The RED-LIP study--pravastatin in primary isolated hypercholesterolemia--an open, prospective, multicenter trial.

The therapeutic effects of the HMG-CoA reductase inhibitor pravastatin on plasma lipids were assessed in an open, prospective, multicenter trial over a treatment period of 3 months. Of a total of 1111 patients, the overall results were calculated from 715 evaluable patients (352 men and 363 women, mean age: 56.1 +/- 11.3 years) with primary isolated hypercholesterolemia (hyperlipoproteinemia type IIa according to Fredrickson) being at high risk for cardiovascular disease according to the classification of the national cholesterol consensus, whose guidelines are distinguishing between three risk levels (low, moderate, and high, respectively) of total-cholesterol (total-c) as well as LDL-c. The treatment period was preceded by a 3-month dietary counselling phase. Treatment with pravastatin significantly reduced total-c (23.8%, p < 0.001), LDL-c (31.9%, p < 0.001) and triglyceride (16.9%, p < 0.001) levels, concomitantly those of HDL-c were significantly raised (15%, p < 0.001). Pravastatin lowered the total-c/HDL-c ratio by nearly 36% from a mean of 8.1 +/- 2.5 to a mean of 5.2 +/- 1.6. At the end 476 patients (66.6%) received the standard dosage of 10 mg/day whereas 140 patients (19.6%) were recorded to take a dose of 20 mg/day. When comparing those patients (n = 456) having maintained consistently a dose of 10 mg pravastatin per day from week 0 to week 12 with patients (n = 113) who received 20 mg/day from week 4 to 12 similar efficacy was observed in both groups (reduction of total-c: 24.5% vs. 22.2%, n.s., reduction of LDL-c: 33.0% vs. 30.0%, n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Prostaglandins and arterial wall lipid metabolism--in vitro, ex-vivo and in-vivo radioisotopic studies.

It is the aim of this paper to review our findings in vitro, in experimental animals and in human on arterial wall lipid metabolism. Radiolabelling of LDL indicates that experimentally induced lesions in hypercholesterolemic rabbits do show less lipid accumulation if treated with prostaglandins (PGI2, PGE1, 13,14-dihydro-PGE1) or stimulators of prostaglandin synthesis (isradipine, a calcium channel blocker of the dihydropyridine family). Endogenous blockade of cyclooxygenase by ASA-pretreatment results in a complete abolishing of this apparently PG-mediated benefit. In-vivo studies using autologous 123I-labeled LDL without therapeutic intervention exhibit a quite good reproducibility of the imaging technique. While PGE1 (at 2 different therapeutic regimens) is inducing lipid lesion regression, the comparable benefit induced by isradipine again disappears with concomitant ASA-therapy. Quantitative estimation of arterial wall lipid metabolism in patients undergoing vascular surgery demonstrates that PGI1- (and cAMP-) increase are paralleled by a several-fold increase of acid and neutral cholesterol ester hydrolase and a decrease in net arterial cholesterol ester content. This benefit again disappears with concomitant ASA-therapy. These findings are allowing to conclude that (exogenously added or endogenously stimulated) prostaglandins do significantly improve arterial wall lipid metabolism.

Alprostadil↗
PubMed1994

Isradipine increases platelet--low-density lipoprotein binding: evidence from ex-vivo studies in humans.

The effects of isradipine (2.5 mg twice daily) on platelet--radioiodine-labeled [123I] low-density lipoprotein (LDL) binding were measured in 16 hypertensive patients (mean age 46.2 +/- 10.7 years) with (cholesterol > 250 mg/dl; n = 8) and without (cholesterol < 200 mg/dl; n = 8) hypercholesterolaemia during 4 weeks of isradipine treatment after 4 weeks of pretreatment placebo followed by 2 weeks of post-treatment placebo periods. Radioligand LDL-binding studies revealed that isradipine induced a significant (p < 0.001) rise in maximum binding capacity (Bmax) from a mean of 1148.6 +/- 244.3 ng protein/10(9) platelets to a mean of 1262.3 +/- 204.1 ng protein/10(9) platelets [dissociation constant (Kd): 9.7 +/- 4.9 micrograms protein/ml before treatment vs 7.8 +/- 3.7 g protein/ml after treatment]. After the post-treatment placebo phase, both Bmax and Kd returned to baseline levels. When the hypercholesterolaemic patients were compared with the normocholesterolaemics, the former revealed a more pronounced increase in platelet [125I]-LDL-binding capacity. Correspondingly, the dissociation constant showed a significantly (p < 0.05) greater decrease. In accordance with these results, both total and LDL cholesterol were reduced after 4 weeks of therapy with significant (p < 0.03) rises through to the end of the post-treatment placebo period. It is suggested that the observed increase in high-affinity platelet--LDL binding with isradipine treatment reflects a state of decreased in-vivo platelet activation, an effect which may be of particular clinical value in hyperlipidaemic patients.

Adult↗