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Biomedical subjects

H Sinzinger

Publications and source records attributed to H Sinzinger.

At least 217 records · Page 12Linked to original sources
PubMed1992

Liver function in acute viral hepatitis as determined by a hepatocyte-specific ligand: 99mTc-galactosyl-neoglycoalbumin.

Twelve patients with recently diagnosed acute viral hepatitis underwent serial 99mTc-galactosyl neoglycoalbumin scanning of the liver (for up to 8 mo). Injection of 99mTc-galactosyl neoglycoalbumin (150 mBq) at a rate of 3.5 mg (50 nmol; 1 ml) revealed that the liver is the exclusive site of tracer uptake. Simulation of 99mTc-galactosyl neoglycoalbumin kinetics allowed quantification of galactosyl neoglycoalbumin binding to human hepatic binding protein. Return of liver function test scores to normal values was associated in two patients with hepatitis A, in four patients with hepatitis B and in two patients with non-A, non-B hepatitis virus infection, with increases in hepatic binding protein concentration (up to three times the initial concentration), binding rate constant and hepatic blood flow. In the other four patients (three patients with hepatitis B and one patient with cytomegalovirus infection) a prolonged course of disease was monitored. In the mean, hepatic binding protein increased from 0.41 +/- 0.11 mumol/L after onset of acute hepatitis (n = 12) to 0.78 +/- 0.21 mumol/L after 6 mo of follow-up (n = 10) (p less than 0.001). During this period, binding rate constant (72.4 +/- 12.6 vs. 82 +/- 11.5 mumol/L/sec; p less than 0.05) and hepatic blood flow (0.027 +/- 0.0051 vs. 0.031 +/- 0.0083 L/sec; p less than 0.05) increased. Hepatic binding protein concentration correlated highly with actual laboratory test results for liver function (r = 0.98; p = 0.0001). We conclude that scintigraphic evaluation of functional liver cell mass using the new receptor-tracer 99mTc-galactosyl neoglycoalbumin could provide an in vivo diagnostic means of quantifying liver function and assessing liver morphology. In addition, our findings suggest that changes in hepatic binding protein-receptor concentration are likely to occur in vivo.

Acute Disease↗
PubMed1992

Platelet PGI2-receptor behaviour change after treatment with acetylsalicylic acid in healthy volunteers.

After treatment of human platelet membrane fractions with different concentrations of acetylsalicylic acid (ASA) the Iloprost binding capacity (Bmax) and also the dissociation constant (Kd) of the high-affinity PGI2-receptor increased significantly (p less than 0.01, low-affinity receptor only an increase of Bmax, p less than 0.01), whereas only a significant (p less than 0.05) increase of the Kd of the high-affinity receptor was observed for intact platelets.

Adolescent↗
PubMed1992

Impaired PGI2-stabilization in septic shock patients.

Lipids, lipoproteins, apolipoproteins and prostacyclin-half-life (PGI2-T/2) in vitro were determined in patients, who suffered from severe circulatory shock. Extremely lowered lipids, lipoproteins and apolipoproteins and an extremely shortened PGI2-T/2 were found, in these patients. These findings support the data of Yui and Aoyama that apolipoproteins may be an important coregulator of the biological half-life of PGI2 and thereby contribute to hemostatic dyregulation seen in these patients.

Apolipoproteins↗
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

Effect of irradiation on the prostaglandin system of human hypernephroma cells.

Specific PGE1-, PGE2-, PGI2-binding sites and the eicosanoid production were investigated in cultured human hypernephroma cells. Low numbers of PGE1-, PGE2- as well as PGI2-high-affinity binding sites and high levels of PG-production were found as compared to normal kidney. Treatment with acetylsalicyclic acid (ASA) significantly (p less than 0.01) increased PGE1-, PGE2- and PGI2-binding sites and inhibited PG-formation. Following irradiation, PG-receptors and eicosanoid generation were significantly (p less than 0.01) diminished, however, were insignificantly lowered in the ASA-treated group. These findings suggest that ASA may modify the radioresponse of cultured hypernephroma cells by preventing the decrease of PG-receptors induced by irradiation.

Aged↗
PubMed1992

Prostaglandin (PG) E1 and 13,14-dihydro (DH) PGE1 are diminishing radiation-induced arterial damage.

Rabbit abdominal aorta was irradiated with single or repeated doses up to 10 Gy. The rabbits were killed at different time intervals after irradiation. 5 micrograms/kg x 6/hr PGE1 or its biologically active metabolite 13,14-DH-PGE1 were administered either 6 hours before or 6 hours after irradiation. The administration of both PGEs reduced radiation-induced mitotic activity (3H-thymidine incorporation) and extracellular matrix [collagen-(14C-proline) and glycosaminoglycan (35-S-sulphate)]-formation as determined by means of autoradiography. The initial peak increase in vascular PGI2-synthesis was partly abolished, while the long lasting depression was less pronounced. 13,14-DH-PGE1 was only slightly less active as compared to the parent compound. Pre-radiation treatment was more effective than post-irradiation therapy. These findings suggest that both the PGs exert significant radiation-protective actions on the arterial wall.

Alprostadil↗
PubMed1992

Isradipine improves platelet function in hypertensives.

The effect of treatment for eight weeks with isradipine 1.25 mg twice daily for 4 weeks and thereafter 2.5 mg twice daily for 4 weeks on ex vivo platelet function was investigated in 10 male hypertensive patients, aged 51 (6.1) y. Systolic and diastolic blood pressure, platelet aggregation in response to ADP, serum thromboxane B2 and beta-thromboglobulin levels were significantly decreased at rest before exercise ergometry, during exercise and at rest after exercise. The platelet count, platelet sensitivity and the plasma levels of 6-oxo-prostaglandin F1 alpha were not affected by isradipine. It is concluded that a compound that lowers blood pressure and inhibits platelet activation may be of clinical benefit in the routine treatment of hypertension.

Analysis of Variance↗
PubMed1992

In vivo quantification of cholesterol content in human carotid arteries by quantitative gamma-camera imaging after injection of autologous low density lipoproteins (LDL).

Low density lipoproteins (LDL) were isolated by immunoaffinity chromatography from 18 patients (31-70 years) suffering from primary hypercholesterolemia with angiographically proven atherosclerosis of either one or both carotid arteries. LDL were labeled with 123I (1 mCi/mg LDL) by the iodine monochloride method followed by purification with dialysis and immediately reinjected thereafter. Gamma-camera serial controls over carotid regions allowed visual detection of uptake of the radiocompound uptake in 12 out of the 18 patients. The lipid entry ratio (LER; counts over the vascular region/pixel as compared to the contralateral side after background subtraction) confirmed the visual findings. Whole body images performed until 20 h after reinjection showed 3 different kinetic types of LDL-influx into the vessel wall: decreasing (type I), increasing and then decreasing (type II) and continuously increasing (type III) with time. Four patients underwent endarterectomy within 2-7 weeks after gamma-camera imaging. Histological control revealed an extensive amount of "foam cells" in tissue samples derived during surgery and an absence of endothelial lining in samples belonging to patients with type II kinetics.

Adult↗
PubMed1992

The diminished extracellular matrix production induced by isradipine, a calcium channel blocker, is completely abolished by cyclooxygenase inhibition.

Collagen and glycosaminoglycan synthesis are well known to be enhanced during early atherogenesis. In this experimental study the synthesis of collagen was determined using 14C proline incorporation, the glycosaminoglycan production by means of 35S-sulphate incorporation and subsequent quantification by means of autoradiography. Isradipine, a new calcium channel blocker of the dihydropyridine family at a dose of 0.3 mg/kg significantly (p less than 0.01) decreased the incorporation of both the radioactive precursors. This effect was abolished by a concomitant aspirin treatment, while aspirin alone did not exert any significant effect on the precursor incorporation. These data suggest that isradipine, which is known to stimulate PGI2 synthesis, may exert this antiatherosclerotic inhibitory action on extracellular matrix production via the endogenous liberation of PGI2.

Animals↗
PubMed1992

Synergism between PGE1-metabolites(13,14-dihydro-prostaglandin E1, 15-keto prostaglandin E1, 15-keto-13,14-dihydro-prostaglandin E1) and nitric oxide (NO) on platelet aggregation.

A synergistic antiplatelet effect between prostaglandins (PG), cAMP-stimulators and nitric oxide (NO), a cGMP-stimulator, has already been described. Data on a synergism between NO and the metabolites of PGE1, however, are lacking so far. We therefore tested the antiplatelet activity of the metabolites of PGE1 alone and their synergism with NO on human platelets of 8 healthy volunteers in vitro. 13,14-DH-PGE1 (ID 50 = 10.8 ng/ml platelet rich plasma (PRP)) was the only PGE1 metabolite inhibiting the ADP-induced platelet aggregation, its efficacy being 76.4% of the parent compound PGE1 (ID 50 = 8.25 ng/ml PRP). NO (ID 50 = 0.52 microM) also inhibited platelet aggregation. The combined addition of 13,14-dihydro-prostaglandin E1 (13,14-DH-PGE1) and NO caused an additive effect. The other PGE1-metabolites tested, 15-keto prostaglandin (15-K-PGE1) (ID 50 = 16.2. micrograms/ml PRP) and 15-keto-13,14-dihydro-prostaglandin(15-K-13,14-DH-PGE1) (ID 50 = 14.8 micrograms/ml PRP), neither had any relevant antiaggregatory capacity themselves nor a synergistic effect with NO. These findings could be of clinical relevance as a NO-synergism may occur not only with therapeutically administered PGE1 but also with its biologically active metabolite 13,14-DH-PGE1.

Adult↗
PubMed1992

Prostaglandin I2 and the nitric oxide donor molsidomine have synergistic effects on thromboresistance in man.

1. In vitro synergistic effects of nitric oxide and prostaglandin I2 (PGI2) have been shown. Consequently we examined any potentiating effect of the nitric oxide donor molsidomine on the reduction in thrombogenicity produced by PGI2 in patients with peripheral vascular disease. 2. Thirty-six patients all with peripheral and also coronary artery disease were randomly allocated to receive PGI2 5 ng kg-1 min-1 for 6 h daily, 5 days a week for 5 weeks, alone (12 patients), with molsidomine 12 mg daily (12 patients) or molsidomine 12 mg daily alone (12 patients). 3. The effect of each treatment regimen was measured in terms of femoral artery platelet uptake and platelet survival after autologous 111Indium-oxine labelling. Molsidomine alone had no effect on platelet uptake or survival but in combination with PGI2 it significantly potentiated the decreased platelet uptake and prolonged platelet survival observed with PGI2 alone.

Aged↗
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↗