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Biomedical subjects

H Sinzinger

Publications and source records attributed to H Sinzinger.

At least 19 recordsLinked to original sources
PubMed1992

13,14-Dihydro-prostaglandin E1 decreases low-density lipoprotein influx into rabbit aorta.

The effect of 4-week daily administration of 13,14-dihydro-prostaglandin E1 (13,14-DH-PGE1; 2 micrograms/kg) on LDL influx into the rabbit aortic wall was examined versus the effect of the same dose of PGE1 and sham-treatment in 108 male animals fed an 1% cholesterol supplemented diet. Treatment was started after de-endothelialization of the abdominal aorta with a Fogarty catheter. After the 1-month treatment period the animals were injected with 10 microCi 125I-low-density lipoprotein (LDL; 0.5 mg protein/ml). Uptake of the radiolabelled LDL was measured in morphologically verified endothelialized, re-endothelialized and de-endothelialized abdominal aortic segments. The LDL influx into the aorta was significantly (P less than 0.001) lower in 13,14-DH-PGE1- and PGE1-treated rabbits than in the controls. This reduction was most pronounced in re- and de-endothelialized segments. No significant difference between effect of PGE1 and of its biologically active derivative, 13,14-DH-PGE1, on arterial LDL entry was found. These data demonstrate a comparable beneficial effect of 13,14-DH-PGE1 and PGE1 on vascular wall lipid metabolism by decreasing LDL entry into the aortic wall in vivo.

Alprostadil↗
PubMed1992

Characterization of prostaglandin (PG)-binding sites expressed on human basophils. Evidence for a prostaglandin E1, I2, and a D2 receptor.

Recent data suggest that prostaglandins (PGs) are involved in the regulation of basophil activation. The aim of this study was to characterize the basophil PG-binding sites by means of radioreceptor assays using 3H-labeled PGs. Scatchard analysis for pure (greater than 95%) chronic myeloid leukemia (CML) basophils revealed two classes of PGE1-binding sites differing in their affinity for the natural ligand (Bmax1 = 217 +/- 65 fmol/10(8) cells; Kd1 = 0.5 +/- 0.2 nM; Bmax2 = 2462 +/- 381 fmol/10(8) cells; Kd2 = 47 +/- 20 nM; IC50 = PGE1 less than PGI2 less than PGD2 less than PGE2 less than PGF2 alpha) as well as two classes of PGI2 (iloprost)-binding sites (Bmax1 = 324 +/- 145 fmol/10(8) cells; Kd1 = 0.5 +/- 0.3 nM; Bmax2 = 2541 +/- 381; Kd2 = 27 +/- 6 nM; IC50 = PGI2 less than PGE1 less than PGD2 less than PGE2 less than PGF2 alpha. In addition, CML basophils exhibited a single class of PGD2-binding sites (Bmax = 378 +/- 98 fmol/10(8) cells; Kd = 13 +/- 4 nM; IC50: PGD2 less than PGI2 less than PGE1 less than PGE2 less than PGF2 alpha). In contrast, we were unable to detect specific saturable PGE2-binding sites. Primary and immortalized (KU812) CML basophils revealed an identical pattern of PG receptor expression. Basophils (KU812) expressed significantly (p less than 0.001) lower number of PGE1 (PGI2)-binding sites (Bmax1: 9% (20%) of control; Bmax2: 36% (50%) of control) when cultured with recombinant interleukin 3 (rhIL-3), a basophil-activating cytokine, whereas rhIL-2 had no effect on PG receptor expression. Functional significance of binding of PGs to basophils was provided by the demonstration of a dose-dependent increase in cellular cAMP upon agonist activation, with PGE1 (ED50 = 1.7 +/- 1.1 nM) and PGI2 (ED50 = 2.8 +/- 2.3 nM) being the most potent compounds. These findings suggest that human basophils express specific receptors for PGE1, PGI2 as well as for PGD2.

Alprostadil↗
PubMed1992

Modification of platelet function by isosorbide dinitrate in patients with coronary artery disease.

The effect of a four weeks oral treatment with 100 mg isosorbide dinitrate (ISDN) daily on platelet function was evaluated in 40 patients (aged 40-65 years) with proven coronary artery disease. Isosorbide dinitrate decreased platelet reactivity to ADP (p less than 0.001), increased platelet sensitivity to PGI2 (p less than 0.01) while the production of TXB2 from exogenous arachidonic acid substrate and from endogenous substrate were both significantly reduced. Circulating platelet aggregates as measured by the Wu-test were markedly reduced (p less than 0.001) but there was little change in the plasma concentration of the platelet proteins beta-thromboglobulin and platelet factor 4. Overall, platelet activation correlated with smoking, hypertension and a family history of coronary artery disease. The reduced platelet activation seen during treatment with isosorbide dinitrate may contribute to the therapeutic benefit seen with this drug in patients with coronary artery disease.

Adenosine Diphosphate↗
PubMed1992

Concomitant aspirin treatment abolishes the antiatherosclerotic effects of the calcium channel blocker isradipine mediated by PGI2.

108 male rabbits, aged 6 months, with experimental hypercholesterolemia and experimental abdominal aortic lesioning received different regimen of antiatherosclerotic treatment; 36 of them were treated with isradipine, a dihydropyridine calcium antagonist (0.3 mg/kg/daily), 36 with isradipine in combination with aspirin whereas 36 animals received placebo. The entry of 125I-radiolabelled LDL into the aorta was demonstrated to be significantly diminished in isradipine-treated rabbits as well as positive Sudan-III-staining and aortic cholesterol content were in comparison to placebo. This benefit was almost completely abolished by concomitant aspirin-treatment. The notable increase in vascular prostacyclin (PGI2) is supposed to mediate the strong antiatherosclerotic effect of isradipine resulting in an inhibition of LDL-entry and vascular cholesterol accumulation. Aspirin almost totally blocked the raise in PGI2-synthesis by the inhibition of cyclooxygenase detected in isradipine-treated animals. It can be concluded, that aspirin-treatment may minimize the antiatherosclerotic actions of calcium antagonists which are mediated by the PG-system.

Animals↗
PubMed1992

Binding of 111In-labeled HDL to platelets from normolipemic volunteers and patients with heterozygous familial hypercholesterolemia.

High density lipoproteins (HDLs; d = 1.063 - 1.21 g/ml) were isolated by ultracentrifugation and radiolabeled with 111In. The in vitro binding onto platelets from healthy volunteers (n = 15) and patients (n = 36) with heterozygous familial hypercholesterolemia (FH) was investigated. Binding was saturable and indicated high-affinity binding sites, which bound 1,882 +/- 361 ng protein of 111In-HDL/10(9) platelets (dissociation constant [Kd] = 7 +/- 3 micrograms protein/ml) in healthy volunteers and significantly (p less than 0.01) lower amounts in the FH patients (1,012 +/- 439 ng protein of 111In-HDL/10(9) platelets [Kd = 12 +/- 4 micrograms protein/ml]; p less than 0.01). The capacity to displace one half of the bound ligand (IC50) amounted to 14 +/- 3 micrograms protein/ml in healthy volunteers and 22 +/- 9 micrograms protein/ml in FH patients (p less than 0.001). Treatment with lipid-lowering drugs (gemfibrozil, alone or in combination with cholestyramine) in 10 patients resulted in an increased HDL binding capacity: before treatment, 1,280 +/- 883; after 2 months of treatment, 2,052 +/- 873 (p less than 0.05); and after 6 months of treatment, 2,127 +/- 812 ng protein/10(9) platelets (p less than 0.01). There was a significant (p less than 0.001) correlation between 111In-HDL binding data and plasmatic lipid and lipoprotein values. Furthermore, those FH patients with the additional risk factors of smoking (p less than 0.05) and hypertension (p less than 0.01) showed significantly lower 111In-HDL binding onto platelets. The findings indicate specific 111In-HDL binding sites for human platelets, which may be decreased in patients with heterozygous FH. Upregulation of HDL binding sites during lipid-lowering medication therapy supports the hypothesis that high-affinity HDL binding is involved in hyperlipemic disorders and is possibly related to the reactivity of platelets.

Adult↗
PubMed1992

Prostaglandin synthesis by the lateral cochlear wall under streptomycin influence.

The synthesis of 4 prostaglandins (PGs), PGD2, PGE2, PGF2 alpha and PGI2, detected as 6keto PGF1 alpha in the guinea pig lateral cochlear wall (LW) was investigated under streptomycin treatment. Animals underwent daily injections of the antibiotic at dosages of 20, 100 and 200 mg/kg body weight. Prostaglandins were detected 1, 5 and 10 days after drug administration using radioimmunoassay. Under aminoglycoside administration a general reduction of PG-synthesis was evident, which was highest for PGI2. Already after 5 days of treatment the PGI2-synthesis was decreased down to 50% under the lowest drug dosage. The highest antibiotic dosage induced an abrupt decline of PGI2 synthesis, down to 26%, in animals with the longest duration of treatment. The significant synthesis reduction of PGI2 was followed by PGE2. The reduction of PG-synthesis seems to be influenced rather by duration than dosage of drug administration. The decreased synthesis of PGs under streptomycin treatment is interpreted as an inhibition of cell membrane phospholipids, the phosphoinositides. This assumption becomes plausible since the phospholipids represent endogenous precursors of the PG-synthesis.

Animals↗
PubMed1992

[Lowering cholesterol with Anticholest--a high fiber guar-apple pectin drink].

In order to determine the efficacy of Anticholest, an apple-pectin-guar soft-drink in reducing elevated cholesterol (c) levels, 33 participants (aged from 8 to 73 years) were divided into three groups of comparable age, body-mass index, total c, LDL-c, HDL-c, and triglycerides. They received this combined fiber product either (group 1) at dosages of 1 cup (17 g) every second day, or (group 2) of 1 cup a day or (group 3) of 2 cups a day. Anticholest significantly reduced total c, LDL-c and the total c/HDL-c ratio. In group 3 HDL-c was increased significantly (p less than 0.01). The average percentage decrease in total c was 10.0% for group 1, 10.7% for group 2, and 15.7% for group 3. LDL-c was lowered 14.4% in group 1, 13.8% in group 2 and 19.1% in group 3. The highest individual reduction amounted to more than 30% for total-c and LDL-c. A significant decrease was also detected in the triglycerides (tg) in group 3 (p less than 0.05). 7 patients were non-responders. Anticholest appears to be an appropriate treatment for patients at risk of coronary heart disease with insufficient or inadequate response to dietary measures, but where long-term pharmacotherapy is not yet indicated. The lack of side effects and its form of administration as a viscous drink are important determinants for long-term compliance, which is essential in the management of a chronic progressive disease such as atherosclerosis.

Adolescent↗
PubMed1992

Antiatherosclerotic actions of isradipine.

Isradipine, a calcium antagonist of the dihydropyridine type, shows antiatherosclerotic actions that interfere with all three main mechanisms of atherosclerosis. These actions are mediated by the release of prostaglandin I2 and endothelium-derived relaxing factor, and the subsequent elevation of intracellular adenosine-3',5'-cyclic phosphate and 3',5'-guanosine monophosphate, respectively. These mechanisms have been proven in vitro and in animal models. Preliminary data in humans suggest that these mechanisms have clinical relevance in the long-term treatment of patients as well.

Arteriosclerosis↗
PubMed1992

[Risk factors of atherosclerosis--primary examination of Vienna employees].

In the course of an atherosclerosis intervention study, a basic medical check-up of 2105 out of 4800 employees of a Viennese banking house was carried out (37.1 +/- 11.0 years, 54.6% females). Apart from liver and kidney function parameters, an extensive lipid status was determined, the blood pressure was measured, and a cardiovascular-centered case history ascertained. The mean cholesterol level in females was 208.3 +/- 54 mg/dl and that in males was 226.8 +/- 61.1 mg/dl. The HDL-cholesterol level in males was 43.8 +/- 11.9 mg/dl; that in females (54.9 +/- 13.4 mg/dl) was significantly higher. The mean value of LDL-cholesterol in the entire group was 141.6 +/- 51.4 mg/dl and it was significantly higher in males, as well as in participants with known hypertension. 33.4% of the persons stated that they smoked. The obtained data will serve not only to discover potential interrelations between the individual risk factors of atherosclerosis in Austria, but also in particular as a basis for interventional strategies on the part of the company's medical services.

Adolescent↗
PubMed1992

Aspirin abolishes the decreased low-density lipoprotein (LDL) entry into the rabbit arterial wall induced by the calcium channel blocker isradipine.

After deendothelialization and experimentally induced hypercholesterolemia in rabbits, an increased LDL entry into the vascular wall can be monitored using radiolabelled LDL. In male rabbits aged 6 months the abdominal aortic endothelium was removed by a Fogarty catheter. The animals fed a 1% cholesterol supplemented diet were treated either with isradipine (0.3 mg/kg/daily) (n = 36) alone or in combination with aspirin (5 mg/kg/daily) (n = 36) for four weeks. Thirty-six animals served as controls. 1, 3, 6, 12, 24 and 48 hours prior to sacrificing, 10 microCi 125I-LDL was administered intravenously to six rabbits in each group. The LDL entry was quantified in the abdominal aorta according to morphologically assessed type of surface lining. Aortic cholesterol content was assessed by Sudan-III staining and quantitative determination. Endothelialized segments exhibited a significantly (p less than 0.05 - p less than 0.001) lower LDL uptake as compared to re- or deendothelialized segments. The LDL entry was significantly lower with isradipine treatment than in controls. In parallel the cholesterol content decreased and the Sudan-III-positive areas were smaller in size. This beneficial effect as well as that on aortic lipid content was abolished by a pretreatment with aspirin. While in the isradipine-treated animals PGI2 synthesis was significantly (p less than 0.01) enhanced, it was almost completely blocked by aspirin. These findings indicate that the benefit of reduced LDL entry caused by isradipine may be mediated by an increased endogenous PGI2 synthesis.

Animals↗
PubMed1979

[Monoclonal gammopathy and platelet function (author's transl)].

This study of 20 patients with monoclonal gammopathy (17 patients with multiple myeloma and 3 patients with Waldenström's syndrome) showed a decreased platlet aggregation induced by ADP and collagen, a reduced platlet retention and a prolonged bleeding time in 25% of the cases in comparison with 30 age- and sex-matched healthy controls. Using Wu and Hoak's technique as increased number of reversible platelet aggregates was observed. There was no relationship between the parameters of primary haemostasis and protein analysis. A disturbed mechanism of primary haemostasis is the main factor responsible for the bleeding diathesis in patients with monoclonal gammopathy.

Aged↗
PubMed1979

[Circulating platelet aggregates during haemodialysis].

In eight chronically haemodialysed patients a significant increase of circulating platelet aggregates (method of Wu and Hoak) was observed immediately after starting haemodialysis. The number of aggregates decreased at the end of haemodialysis reaching the starting values after 360 min. The platelet interaction with the dialysis membrane surface might cause this phenomenon. Anticoagulation with heparin alone was insufficient in preventing aggregate formation during haemodialysis.

Adolescent↗