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Biomedical subjects

H Sinzinger

Publications and source records attributed to H Sinzinger.

At least 199 records · Page 11Linked to original sources
PubMed1994

Isradipine decreases the entry of radioiodine-labelled low-density lipoproteins into the arterial wall.

Experimental studies have demonstrated that isradipine significantly decreases the entry of radioiodine-labelled (125I) low-density lipoproteins (LDL) into the aorta. This study aimed to investigate whether similar effects could be detected in humans as well. Twelve patients (nine men and three women, aged from 35 to 53 years), all of whom had both hyperlipoproteinaemia (either type IIa or type IIb; mean total cholesterol: 296 +/- 25 mg/dl; mean LDL cholesterol: 208 +/- 22 mg/dl) and mild-to-moderate hypertension [mean systolic blood pressure (SBP): 149 +/- 12 mmHg; mean diastolic blood pressure (DBP): 104 +/- 4 mmHg] received isradipine (2 x 2.5 mg). Autologous radiolabelled (123I) LDL was reinjected and a gamma camera used to study the LDL kinetics before (at 20 min, 2 h and 20 h) and after (at the same time intervals) treatment with isradipine. Of interest were those arterial regions that are typically sites of atherosclerotic lesions (carotid artery, femoral artery). Results revealed three different types of LDL kinetics which were not altered by isradipine treatment. The quantitative LDL entry, however, was reduced by at least 4.7% with a maximum of 23.5% (p < 0.01). Only five vascular sites with type III kinetics were detected. These data suggest that isradipine may induce functional regression of atherosclerotic lesions.

Adult↗
PubMed1994

Influence of calcium antagonists on platelet function and vascular prostacyclin production.

It is suggested that calcium antagonists can counteract the process of atherogenesis by influencing different cellular mechanisms, for example, inhibiting cellular migration and proliferation, as well as by having beneficial effects on lipid metabolism and platelet function. In an assessment of the activity of different calcium antagonists in various platelet function tests and prostacyclin (PGI2) synthesis, amlodipine, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nitrendipine and verapamil were tested in vitro for their effects on adenosine diphosphate (ADP)- or collagen-induced platelet aggregation, malondialdehyde (MDA) formation and vascular PGI2 production. Nitrendipine, isradipine and nicardipine were shown to inhibit both ADP- and collagen-induced platelet aggregation at the lowest concentration (0.5 microgram/ml). The half-maximum inhibiting concentration (IC50) of isradipine (4.78 +/- 0.36 micrograms/ml for ADP-induced platelet aggregation) was significantly (p < 0.01) lower than the IC50 of all the other drugs. Nitrendipine, with an IC50 of 44.2 +/- 5.32 micrograms/ml, and nicardipine, with an IC50 of 46.74 +/- 3.83 micrograms/ml, were respectively the second and third most effective compounds. Formation of MDA was also inhibited the most by isradipine, which exerted its inhibitory properties at one-fifth the concentration needed with the other agents: the IC50 of isradipine was 0.98 +/- 0.16 microgram/ml, which was significantly different (p < 0.05) compared with the second most effective agent, verapamil, which had an IC50 of 14.92 +/- 3.78 micrograms/ml. In-vitro PGI2 production was stimulated the most by isradipine as well, producing a significant (p < 0.01) increase to 417.8 +/- 47.6 pg/mg tissue/h (control: 296.4 +/- 17.6 pg/mg tissue/h) at a concentration of 0.5 microgram/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1993

Etofibrate increases binding of low and high density lipoprotein to human platelets of patients with type II hyperlipoproteinemia.

Previous work suggested an influence of etofibrate, a diester of nicotinic acid and clofibric acid, on lipoprotein receptors. Besides its beneficial effects on plasma lipoprotein levels of decrease in total cholesterol, LDL-cholesterol and triglycerides and increase in HDL-cholesterol, etofibrate was shown to inhibit platelet function. In order to further evaluate platelet-lipoprotein interactions, the effects of etofibrate on plasma lipids and lipoproteins on the specific binding of normal [111In]LDL and [111In]HDL onto platelets as well as its effect on platelet function were evaluated in 8 patients affected by Type II hyperlipoproteinemia (HLP). In all patients binding was saturable and indicated high affinity binding sites capable of binding 927 +/- 233 ng protein of [111In]LDL/10(9) platelets (Kd 12 +/- 3 micrograms protein/ml) and 1496 +/- 435 ng protein of [111In]HDL/10(9) platelets (Kd 14 +/- 3 micrograms protein/ml). The capacity of native LDL (HDL) to displace bound [111In]LDL ([111In]HDL) by half (IC50) amounted to 22 +/- 9 micrograms protein/ml (26 +/- 8 micrograms protein/ml). Following a 6-week treatment period with etofibrate (500 mg twice daily), decrease in plasma total cholesterol, LDL-cholesterol and apolipoprotein (apo) B and increase in HDL-cholesterol and apo AI was correlated to a significant (P < 0.01) increase in LDL- as well as HDL-receptor binding. The platelet binding capacity increased to 1085 +/- 212 ng protein/10(9) platelets (Kd 8 +/- 3 micrograms protein/ml) for [111In]LDL and to 1867 +/- 266 ng protein/10(9) platelets for [111In]HDL (Kd 11 +/- 3 micrograms protein/ml). Platelet function studies demonstrated significantly (P < 0.01) reduced platelet aggregation in response to ADP and thromboxane formation after 6 weeks of etofibrate therapy. These findings in patients with HPL Type II indicate in vivo upregulation of specific [111In]LDL as well as [111In]HDL binding sites on human platelets associated with reduced platelet activation following etofibrate therapy.

Adult↗
PubMed1993

Scintigraphic evaluation of functional hepatic mass in patients with advanced breast cancer.

Recent studies suggest a high specificity of 99mTc-galactosyl neoglycoalbumin (99mTc-NGA) receptor scanning in vivo by providing both morphological and functional diagnosis of liver disease. In 22 patients with advanced breast cancer 99mTc-NGA (150 MBq; 50 nmol) was exclusively trapped by the liver, the images showing 'cold spots' in areas of liver metastases formation. A two-tailed analysis was performed: the time activity curves recorded for the liver and precordial area were subjected to a kinetic receptor-calculating model allowing an estimation of the NGA-receptor concentration of the liver (i.e. hepatic binding protein, HBP) as well as calculation of the residual functional liver volume (RFLV) via the S.P.E.C.T.-study. In breast cancer patients with liver metastases a significantly (P < 0.01) lower HBP-concentration was estimated (0.65 +/- 0.16 vs 0.82 +/- 0.17 mumol l-1) as evidenced by a lower 99mTc-NGA-accumulation in the liver resulting also in a significantly (P < 0.001) lower RFLV (739 +/- 348 vs 1336 +/- 184 ml). In four amonafide-treated patients (800 mg m-2 intravenous infusion over 3 h) approximately one week after one chemotherapy cycle a significant (P < 0.05) increase in HBP-concentration (0.56 +/- 0.10 vs 0.72 +/- 0.06 mumol l-1) of the liver was found corresponding with an increase in RVLF (546 +/- 297 vs 670 +/- 265 ml). These regulatory mechanisms at the HBP level measured in vivo provide further evidence that 99mTc-NGA should have promise as a clinically useful receptor radiopharmaceutical for both quantification of liver function and assessment of liver morphology.

Aged↗
PubMed1993

Lipoproteins and prostacyclin stability.

PGI2 is an important local mediator keeping circulating blood cells apart from the vessel wall, thus regulating hemostasis. Alterations of locally available amounts of this compound may be associated with either bleeding or thrombotic events. Factors influencing synthesis, transmission, and degradation coregulate the amount of biologically active PGI2 available at a certain vascular site. Plasmatic T1/2 of PGI2 is shortened either due to an inherited disorder or an acquired disease, its underlying cause being unknown. Generally, this is associated with thrombotic events and extremely low concentrations of both HDL cholesterol and apoA1. In contrast, the only patient we saw with a prolonged PGI2 T1/2 repeatedly experienced extremely severe bleeding complications. Recovery from severe diseases such as shock and malaria, for example, results in normalization of both PGI2 T1/2 and lipoprotein (HDL) and apoA values. Although these findings have not yet been verified at a molecular level, it is likely, that apoA1 contributes to the stabilization of PGI2 in human blood, thus representing one further link between lipid metabolism and hemostasis.

Adult↗
PubMed1993

Increase in in vivo low-density lipoprotein (LDL) receptor binding after PGE1 and 13,14-dihydro-PGE1 treatment in rabbits.

In a total of 48 male rabbits, the influence of PGE1 and its metabolite, 13,14-dihydro-PGE1, on the liver LDL receptor was examined in vivo. One-half of the animals were fed a 1% cholesterol-enriched diet for 4 weeks, and the other 24 animals received their normal chow. One-third of the animals in both groups received PGE1 (5 micrograms/kg i.v.), another 13,14-dihydro-PGE1 (5 micrograms/kg i.v.), and the third was a control group receiving placebo injections only. The LDL-receptor activity (total LDL uptake by the liver vs. blood activity) after injection of radiolabelled [125I]LDL and LDL disappearance from plasma were quantified. In the cholesterol-supplemented animals, the radioactive LDL uptake was significantly (p < 0.001) lower compared to the control group. Both PGE1 and 13,14-dihydro-PGE1 caused a comparable increase in LDL uptake, the extent being more pronounced in the hypercholesterolemic animals. LDL disappearance in normocholesterolemic animals was much faster than in cholesterol-fed animals. Both of the PGs caused a faster disappearance, the extent being comparable. As a mechanism of action, an induction of messenger RNA for the receptor protein by the prostaglandins is discussed. These results indicate a hypolipidemic action of PGE1 and its biologically active metabolite at the receptor level.

Alprostadil↗
PubMed1993

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

Low density lipoproteins (LDLs) were isolated by ultracentrifugation and radiolabeled with 111In. The in vitro binding of these radiolabels onto platelets of normolipemic volunteers (n = 15) and patients (n = 36) with heterozygous familial hypercholesterolemia (FH) was investigated. Binding was saturable and indicated high-affinity binding sites capable of binding 1,757 +/- 289 ng protein of 111In-LDL per 10(9) platelets (dissociation constant [Kd], 6 +/- 3 micrograms protein/mL) in healthy volunteers and significantly (p < 0.001) lower amounts in the FH patients (mean, 633 +/- 341 ng protein/10(9) platelets; Kd, 10 +/- 5 micrograms protein/mL). The capacity of native LDL to displace bound 111In-LDL by half amounted to 10 +/- 4 micrograms protein/mL in volunteers and 22 +/- 8 micrograms protein/mL in FH patients (p < 0.001). Treatment with gemfibrozil alone or in combination with cholestyramine in 10 patients resulted in increased 111In-LDL binding by platelets (470 +/- 307 [mean +/- SD] ng protein/10(9) platelets before therapy, 948 +/- 650 ng protein/10(9) platelets after 2 months of therapy [p < 0.01], and 1,272 +/- 701 ng protein/10(9) platelets after 6 months of therapy [p < 0.01]). Significant correlations between 111In-LDL binding capacity and apolipoprotein B (r = -0.83, p < 0.001) and LDL cholesterol (r = -0.80, p < 0.000) concentrations were found. Patients with clinically manifested atherosclerosis (p < 0.01) and those with diabetes mellitus (p < 0.05) had significantly lower platelet LDL binding sites. The findings demonstrate 111In-lipoprotein-specific binding sites on human platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[Gender-specific differences of risk factors of atherosclerosis. A study of 3,850 Vienna employees].

Atherosclerosis is the most frequent cause of death in Austria as well as in the other western industrialized countries. Sex specific differences in the various age groups concerning relative myocardial infarction-mortality stimulated us to investigate the risk factors for atherosclerosis in 3850 employees. An extensive lipid status, liver and kidney function parameters were determined, the blood-pressure was measured, and a cardiovascular centered case history was examined. The mean cholesterol level and the LDL-cholesterol level in males were significantly higher than in females (cholesterol: males 223.8 +/- 56.8 mg/dl, females 208.2 +/- 43.3 mg/dl, LDL-cholesterol: male 151.9 +/- 55.1 mg/dl, female 132.2 +/- 40.1 mg/dl, p < 0.001). The mean HDL-cholesterol level in males were significantly lower than in females (males: 45.0 +/- 11.6 mg/dl, females 56.2 +/- 13.3 mg/dl, p < 0.001). No significant difference concerning smoking-behaviour could be determined between female and male participants in this cohort (33.0% of the males resp. 33.6% of the females stated that they smoked cigarettes). Hypercholesterolaemia and cigarette-smoking are the main risk factors for both sexes, however the situation of women-except for the 6th decade-is much better than that of men. Remarkable is the increasing number of female-smokers, especially at younger age.

Adult↗
PubMed1993

Coffee, lipoproteins and cardiovascular disease.

Morbidity and mortality of cardiovascular diseases are related to life-style (in particular diet, exercise and smoking). Many epidemiological studies have demonstrated that nutrition significantly affects cholesterol (C) and lipoprotein levels i.e. LDL-c and HDL-c, whereby an increase in LDL-c and a decrease in HDL-c represent independent primary risk factors for atherogenesis. For many years studies have been performed to discover other risk factors, one of the most important being the influence of coffee consumption. Epidemiological analysis of a single dietary factor produces many methodological difficulties, which may explain the inconsistent study findings regarding the effects of coffee. Thus, these studies have to be performed with large numbers of participants over many years, during which time dietary and drinking habits have to be stabilized in order to detect possible associations. Coffee contains a number of biochemically active substances, one of the most important being caffeine, a xanthine derivative. Recent studies have concentrated on the methods of preparation of coffee, which vary from country to country. A lipid fraction of boiled coffee, which is widely consumed in Northern European countries has been shown to significantly raise C and LDL-c in a dose-dependent manner. Filtered coffee, however, does not contain this lipid elevating fraction. Thus, recommendations concerning the consumption of coffee have to take into account the particular method of preparation, the amount consumed and predisposing risk factors that could interact with coffee consumption such as hypertension, hyperlipidaemia, cardiac arrhythmia.

Cardiovascular Diseases↗
PubMed1993

[Radiosynovectomy with dysprosium-165 iron hydroxide].

Treatment of chronic rheumatoid synovitis (RS) is directed to control the inflammatory process causing pain and disability. Radiation synovectomy is suggested to be an alternative to surgical treatment, but its clinical use has been restricted because of significant leakage (> 10%) associated with the use of the standard radionuclide 90-Yttrium (used as 90-Yttrium silicate colloid) and because of its long physical half-life of 64 hours prolonging the patients' stay in the hospital. 165-Dysprosium possesses promising nuclear properties for the treatment of patients suffering from RS. The maximum soft tissue penetration of its beta-particles is 5.7 mm which is the range being necessary to penetrate the inflamed synovia. Using as carrier ferric hydroxide macroaggregates (DFH) 165-Dy is expected to minimize the cumulative radiation dose to non-target organs by its very low leakage. Animal studies were performed in 13 rats and 6 rabbits to obtain the rationale and safety data for its clinical evaluation. These studies revealed that 98.2 +/- 0.6% of the injected dose remained in the joint with a nontarget organ uptake of less than 0.1%. Clinical results were obtained from 8 patients with rheumatoid arthritis. 24 hours after injection scintigraphy was performed over the treated joint and the liver region revealing no detectable leakage of the injected activity from the joint. Blood pool activity was also assessed revealing a leakage of 0.02% of the dose injected in the knee 24 hours after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Screening for risk factors in agricultural schools of 5 Austrian federal counties ].

While screening activities have already been performed in a wide range in adults in Austria, extensive investigations in children and juveniles have so far only been done in a very limited number. In 1094 out of 1732 juveniles attending agricultural schools all lipid parameters were fully documented and thus could be evaluated. On an average, the total cholesterol (169 mg/dl) was too high; the worst findings for lipid parameters cholesterol, HDL-cholesterol, triglycerides, apolipoprotein-A1 were found in pupils of Burgenland. The cholesterol/HDL-cholesterol ratio in Burgenland was significantly (p < 0.01) higher than in Lower Austria. Female participants had a higher total cholesterol, HDL-cholesterol, and apolipoprotein-A1, but lower triglycerides and also lower blood pressure. Juveniles with a positive family history showed lower total cholesterol, but higher triglycerides as well as HDL-cholesterol. In heavy smokers, but also in occasional smokers, a lower total cholesterol, but decreased HDL-cholesterol and apolipoprotein-A1 and increased triglycerides were found. These findings underline the high prevalence of hypercholesterolemia in juveniles justifying screening activities and possibly therapeutic intervention at this young age.

Adolescent↗
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

Ticlopidine and platelet function in healthy volunteers.

The influence of a 4-weeks therapy with 500 mg ticlopidine daily on platelet function parameters was examined in 10 male healthy volunteers aged 20-33 years in order to extend the knowledge on the antiplatelet activity of this substance. Ticlopidine significantly (p less than 0.01) affected ex-vivo platelet aggregation induced by ADP and increased platelet sensitivity to the antiaggregatory action of PGI2. Generation of TXB2 from endogenous substrate during spontaneous clotting of blood (serum-TXB2), conversion of exogenous radiolabelled arachidonic acid into TXB2 and MDA-formation in isolated platelets were unaffected by the treatment. The TXB2-level in plasma of volunteers, however, was decreased, after administration of the drug. The diminished alpha-granule content liberation (beta-thromboglobulin: p less than 0.01; PDGF: p less than 0.01; PF4 not significant) indicates that ticlopidine induces a decrease in platelet activity. The beneficial effect on release reaction is not associated with a decrease in TXA2-formation. Our results demonstrate that ticlopidine inhibits platelet activity, especially the PDGF-release. These results confirm the value of this drug in the prevention of atherosclerosis and its thromboembolic complications.

Adult↗
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↗