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Biomedical subjects

H Sinzinger

Publications and source records attributed to H Sinzinger.

At least 163 records · Page 9Linked to original sources
PubMed1996

Prostaglandin I2-mediated upregulation of 125I-LDL-receptor binding by isradipine in normo- and hypercholesterolemic rabbits in vivo.

The in-vivo low-density lipoprotein (LDL)-uptake by the liver was monitored during the initial 60 minutes after injection of radiolabelled LDL. LDL-uptake by the liver as evidenced by the liver/blood pool ratio in normocholesterolemic male New Zealand white rabbits (44.2 +/- 3.1% of whole body activity) was almost double as compared to the ones fed a 1% cholesterol enriched diet (22.5 +/- 3.3%). The blood disappearance of 125I-LDL was significantly faster in normocholesterolemic animals. A 4-week treatment with the dihydropyridine calcium channel blocker isradipine resulted in a significantly enhanced LDL-binding by the liver, both in normo- and hypercholesterolemic animals to a comparable extent. A concomitant acetylsalicylic acid (ASA) treatment completely abolished the benefit induced by isradipine while ASA alone was ineffective. Similarly, 125I-LDL disappearance from blood was improved by isradipine, while ASA neutralizes this effect. Again, ASA alone did not change the kinetics. Plasma cholesterol and high-density lipoprotein (HDL) cholesterol remained unchanged. Isradipine significantly enhanced vascular prostaglandin(PG)I2-generation while concomitant ASA treatment or ASA application alone almost completely depressed PGI2-formation. It is concluded that the improved LDL-binding by the liver is due to an enhanced PGI2-formation evoked by isradipine.

Animals↗
PubMed1996

Dynamic changes of plasma lipids and lipoproteins in patients after transient ischemic attack or minor stroke.

PURPOSE: Only few data are available concerning variations of lipids and lipoproteins in the acute stage after ischemic cerebrovascular events. It was the aim of this study to investigate whether the lipid and lipoprotein levels obtained in the first few days after a transient ischemic attack (TIA) or a minor stroke (MS) actually reflect "correct' values or "changed' (ie, false low) values, as in patients after acute myocardial infarction. PATIENTS AND METHODS: Total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), and triglyceride (TG) levels of 37 unselected patients with TIA or MS were determined within 12-48 hours (Group A) or within 49-168 hours (Group B) after the acute event. After a mean observation period of 15.3 months, all patients were re-examined; the results were compared with those of the baseline evaluation. RESULTS: At the time of the baseline evaluation, TC and LDL-C levels of Group B patients were significantly lower than Group A levels. At the end of the observation period, however, Group A and Group B patients did not differ with regard to all four parameters. In comparison with the baseline examination, the values of Group A patients had not changed. In Group B patients, however, TC, HDL-C, LDL-C, and TG levels had significantly increased. CONCLUSION: Our results strongly suggest that lipid and lipoprotein levels of patients with TIA or MS should be assessed within a maximum of 48 hours after the acute event. If the examination cannot be performed within that period, the determination of reliable values is possible only after several weeks or months.

Adult↗
PubMed1996

Is a (n inborn) deficiency of prostacyclin synthesis stimulating plasma factor associated with increased lipoprotein(a)?

Patients with the antiphospholipid syndrome as well as those with a lack in the prostacyclin synthesis stimulating plasma factor (PF) are prone to develop thrombophilia and are at a higher clinical risk for vascular disease. As patients with the antiphospholipid syndrome have been reported to show elevated lipoprotein (Lp)(a) levels, we re-examined all our patients known to have an inborn or an acquired persistent deficiency of PF. Their non-affected relatives served as controls. In addition, 36 patients suffering from clinically manifested atherosclerosis as well as 16 healthy adults, all of them having elevated Lp(a) levels (> 30 mg/dl), were screened for a PF deficiency. In fact, all the patients with a deficient PF activity showed elevated Lp(a) values. While the prevalence of PF deficiency ranges about 1-2%, in 7 (19%) patients with clinically manifested atherosclerosis and 3 (19%) healthy adults with elevated Lp(a) this defect was found. The findings demonstrate an association between PF deficiency and Lp(a), indicating a biochemical interaction which needs to be further elucidated.

Adolescent↗
PubMed1996

Evidence that cyclosporine inhibits periodontal prostaglandin I2 synthesis.

Cyclosporine (CsA) is a selective immunosuppressant widely used in clinical therapy. Like phenytoin and nifedipine, the drug is associated with gingival overgrowth. This study considers the interaction of CsA and prostaglandin I2 (PGI2), in particular the action of the drug on gingival tissue in vitro and in vivo. The PGI2-synthesis of rat, rabbit and human gingival tissue was examined by bioassay. In vivo CsA-therapy reduces gingival PGI2-synthesis. The results furthermore show a dose-dependent inhibition of PGI2-synthesis by CsA (1-100 micrograms/ml) in vitro. PGI2-synthesis from in vivo CsA-pretreated probes was further dose-dependently diminished by in vitro addition of CsA. As PGI2 exerts an antiproliferative activity via cAMP-elevation, the drug-induced inhibition of PGI2 production is claimed to be responsible for gingival hyperplasia in CsA-treated patients.

Adult↗
PubMed1996

Low cholesterol and cancer.

PURPOSE: The relation between plasma cholesterol (CH) concentration and mortality is complex. The plasma CH concentration correlates positively with mortality from coronary heart disease, but some studies have shown a negative relation with death from cancer. If these two relations reflect causal mechanisms that are reversible by changing the plasma CH concentration, the benefits of lipid reduction for heart disease might be offset by an increased mortality from cancer. Different aspects between lipid metabolism and cancer, as well as new insights into this interesting field, are discussed. METHODS: The literature was searched using MedLine through 1966 and January 1996. RESULTS: There is no evidence from the data available at present that the association between low CH and a higher risk of cancer is causal. CONCLUSION: This issue should not affect the advice on health matters offered by doctors, especially to patients with other risk factors for cardiovascular disease. The possibility that hypercholesterolemia (HC) drugs can induce a reduction of tumor-cell growth makes them potentially useful as an adjuvant to chemotherapy and ultimately increases the probabilities in the prevention and treatment of cancer.

Animals↗
PubMed1996

Imaging of atherosclerosis (Part I).

Atherosclerosis is the leading cause of morbidity and mortality in the Western World. Standard imaging techniques such as angiography, ultrasonography and computed tomography are still not effective in detecting atheromatous plaques in their early stages of development, when the lesions are most metabolically active and therapeutic interventions could beneficial. These techniques identify morphological changes such as increased wall thickness, decreased luminal diameter or related haemodynamic changes such as turbulence of blood flow. Unfortunately, all these phenomena occur when the plaque has evolved and encroaches on the lumen. There is a need for non-invasive methods that could assess the presence and the extension of atherosclerotic disease in its early stages, when the lesions are in their metabolically most active stage but still do not narrow the diameter of the lumen. Part I of this article presents an overview of the diagnostic procedures angiography, sonography, computed tomography and magnetic resonance tomography in imaging atherosclerotic lesions. Part II will concentrate on the diagnostic possibilities of scintigraphic imaging and positron emission tomography.

Animals↗
PubMed1996

Imaging of atherosclerosis (Part II).

Several methods are currently used to detect and quantitate atherosclerosis. Standard methods like angiography, computed tomography and sonography are described in part I of this paper. Angiography, still considered to be the "gold standard" to detect atherosclerotic lesions is invasive, involves potential risks for the patient and cannot be used in asymptomatic subjects even though they may be at high risk to develop atherosclerosis. Computed tomography and sonography are suitable to define morphological alterations of atherosclerotic lesions, but they are unfit to characterize their functional stage. Functional methods such as scintigraphy (planar and single-photon-emission tomography), positron emission tomography, and magnetic resonance imaging (reviewed in Part I) partly fulfil the claim to image early atherosclerosis. Preliminary evidence indicates that radioisotopic techniques and magnetic resonance imaging may be of great benefit in the future for elucidating functional aspects of this widespread disease. The functional diagnostic procedures available today are reviewed in this paper.

Animals↗
PubMed1996

Passive smoking, platelet function and atherosclerosis.

Active smoking is a well known risk factor for the development of atherosclerosis and in particular coronary heart disease and peripheral vascular disease. The negative effects of active smoking demonstrated on platelet function, the eicosanoid system and platelet thromboxane A2 generation may contribute to the hemostatic imbalance reported. Recently, the problem of passive smoking as a health risk has been widely discussed. Detailed information on the role of passive smoking on hemostatic parameters, however, is still very limited. As far as present knowledge is concerned, platelet activation seems to be significantly involved in the deleterious vascular effects of passive smoking as well.

Arteriosclerosis↗
PubMed1996

[Single passive smoking exposure induces no measurable oxidation of low density lipoproteins].

Oxidation of low-density lipoproteins (LDL) is well known to increase the atherogenic risk. Active smoking has been claimed to be associated with a significant oxidant stress determined by enhanced LDL oxidation and isoprostane formation. We assessed the susceptibility of LDL to oxidation in 9 healthy non-smokers and 7 smokers before and after three and five hours' exposure to passive smoking. Baseline values for the lag time, diene formation, malondialdehyde and isoprostanes differed in part significantly. In contrast to the data on active smoking, passive exposure to cigarette smoke did not significantly affect any of these parameters, nor diene formation and electrophoretic mobility in smokers and non-smokers alike. These results indicate that a single exposure to passive smoking does not induce relevant oxidation of LDL in men.

Adult↗
PubMed1995

Isradipine increases vascular prostaglandin I2-formation while the thromboxane B2-synthesis is diminished.

PGI2- and TXA2-synthesis from vascular tissue samples derived from cultured (endothelial and smooth muscle) cells, rabbit aorta and human bypass surgery were determined using specific radioimmunoassays for the stable derivatives (6-oxo-PGF1a and TXB2, respectively) of these compounds. Cultured cells were incubated in presence of isradipine, rabbits were pretreated for 4 weeks receiving 0.3 mg isradipine/kg*day, while patients were on isradipine (5-10 mg total dose/day, per os twice daily) since 6-19 weeks. In presence of isradipine, cultured cells produced significantly (p < 0.01) more 6-oxo-PGF1a and significantly less TXB2 (p < 0.05). 6-oxo-PGF1a-formation in rabbit aorta was significantly (p < 0.01) higher in isradipine treated normocholesterolemic animals while no significant changes were seen in isradipine treated hypercholesterolemic animals. TXB2 was significantly (p < 0.01) depressed in the abdominal and the thoracic aortic segment of isradipine treated hypercholesterolemic animals and was not significantly influenced in isradipine treated normocholesterolemic animals. Similarly, PGI2-synthesis in human arterial specimen was significantly (p < 0.01) enhanced as compared to the untreated controls. These findings indicate a beneficial behaviour of isradipine on vascular wall eicosanoid profile, which may contribute to a variety of antiatherosclerotic actions at the vascular wall level and to an improvement in hemostatic balance already described.

Aged↗
PubMed1995

Passive smoking and cardiovascular risk.

A possible relationship between passive smoking and coronary heart disease has been widely debated during the past decade. Convincing evidence links environmental (passive) tobacco smoke exposure to heart disease morbidity as well as mortality. In the United States, 37,000 coronary heart disease deaths per year are attributed to environmental tobacco smoke exposure, accounting for 70% of all deaths caused by environmental tobacco smoke. The analysis of 10 epidemiologic studies indicated a consistent dose-response effect related to exposure, but more proof is still needed. Evidence indicates that nonsmokers are more sensitive to smoke, including cardiovascular effects, and that sidestream smoke contains higher concentrations of gas constituents, including carbon monoxide. Pathophysiological and biochemical data after short- and long-term environmental tobacco smoke exposure show changes in endothelial and platelet function as well as exercise capacity similar to those in active smoking. Therefore, passive smoking is a relevant risk factor for heart disease morbidity and mortality.

Animals↗
PubMed1995

Evidence for lipid regression in humans in vivo performed by 123iodine-low-density lipoprotein scintiscanning.

Radiolabeling of autologous LDL allows in vivo characterization of arterial wall lipid metabolism and LDL receptor imaging. Different kinetic types of arterial wall LDL entry reflect the de-, re-, and endothelialized segments in both animals and humans. In 36 male cholesterol-fed rabbits being treated with the calcium channel blocker isradipine (0.3 mg/kg daily), the retention of the radiolabeled (125I-LDL) was reduced, being related to the reduction in arterial wall cholesterol ester content and the decreased extent of Sudan III-positive areas. In parallel, a significant (p < 0.01) increase in vascular prostaglandin I2 (PGI2) generation was seen in endothelialized and reendothelialized segments of the abdominal aorta. These effects were completely abolished by concomitant treatment with acetylicsalicylic acid (ASA). These data could be confirmed in humans, too: a 4-week treatment with prostaglandin E1 (PGE1:5 ng/kg/min iv, 5 days/week, 6 h/day for 6 weeks) and isradipine (2 x 2.5 mg po daily for 4 weeks) did not change arterial 123I-LDL influx kinetics, which were examined over a total of 60 (PGE1) and 96 (isradipine) vascular regions. In contrast to this, the retention of the tracer was significantly diminished in different arterial segments. In isradipine-treated patients, 20 hours after reinjection of radiolabeled LDL, the quantitative LDL entry was reduced by at least 4.7% with a maximum of 23.5% (p < 0.01) in type I (n = 50 lesions) or type II lesions (n = 41). PGE1 treatment induced a 16.9% to 30.7% (p < 0.01) decrease of LDL retention in type I (n = 36 lesions) or type II lesions (n = 24), respectively. These findings support the hypothesis derived from earlier experimental studies that the antiatherosclerotic effects are likely to be due to the increase in PGE1 and/or PGI2 availability mediated by an increase in cAMP. The results demonstrate the potential of 123I-LDL scintigraphy for the characterization of vascular LDL kinetics and the monitoring of functional lipid lesion regression.

Alprostadil↗
PubMed1995

Atherogenic risk reduction in patients with dyslipidaemia. comparison between bezafibrate and lovastatin.

OBJECTIVE: To examine the atherogenic risk-reducing effect of bezafibrate and lovastatin. DESIGN, SETTING, PATIENTS, INTERVENTIONS: Double-blind, randomized clinical trial of male and female patients with moderate hypercholesterolaemia with or without hypertriglyceridaemia. Two months dietary treatment followed by 400 mg sustained release bezafibrate every day or 20 mg lovastatin every day for 6 months. Patients recruited (n = 561) and treated (n = 524) by primary care physicians throughout Austria. MAIN OUTCOME MEASURES: Multifactorial assessment of atherogenic risk profile. RESULTS: Bezafibrate increased high density lipoprotein cholesterol by 16%, lovastatin by 10% (P < 0.05). Bezafibrate decreased low density lipoprotein cholesterol by 20%, lovastatin by 27% (P < 0.001). Bezafibrate decreased total cholesterol by 15%, lovastatin by 18% (P < 0.001). Bezafibrate reduced triglycerides by 29%, lovastatin by 13% (P < 0.001); and fibrinogen by 9.4% and 3.0%, respectively. Fibrinogen reduction as a result of bezafibrate administration was dependent on starting levels. The risk ratio cholesterol:high density lipoprotein cholesterol (baseline both 6.1) reduction was 27% in both groups. The low:high density lipoprotein ratio (baseline: 4.1/4.2) reduction reached 31% and 34% respectively. Coronary events' probability (calculated from multifactorial risk functions) were greatly reduced by both agents (41%/33%). Hypertriglyceridaemic patients had a higher initial global coronary risk and profited more from treatment. Bezafibrate was significantly better tolerated (P < 0.001) than lovastatin; most events were gastrointestinal (6 vs 14, ns) or as a result of creatine phosphokinase elevations (3 vs 12, P < 0.05). CONCLUSIONS: Both treatments significantly reduced the risk parameters for developing coronary heart disease, and calculated multifactorial coronary risk was similarly decreased. When selecting a drug for moderate dyslipidaemia and if haemostatic regulation is disturbed, the additional effect of bezafibrate on elevated fibrinogen levels should be considered.

Adult↗
PubMed1995

Arterial wall rather than platelets is responsible for diminished thrombogenicity during isradipine therapy.

We investigated whether the vessel wall or platelets are primarily responsible for the decreased thrombogenicity induced by the calcium channel blocker isradipine after endothelium removal. In a cross-perfusion model, rabbit aorta and iliac artery endothelium of receiver animals were removed by balloon catheter before being perfused with the blood of the blood donor rabbits. Donor and/or receiver animals were treated with 0.3 mg/kg isradipine intravenously (i.v.) daily for 1 week or with 10 mg acetylsalicylic acid (ASA) in addition. The other animals received vehicle only or ASA. The animals were divided into four groups (I-IV, total n = 24) consisting of four subgroups of 6 animals each. In all, 96 rabbits were examined. Immediately after the last administration of the respective drug, native blood from a donor rabbit was circulated (30 ml/min) through a deendothelialized segment of a receiver rabbit. The contract (C) and spread (S) platelets as well as the denuded surface covered with platelet aggregates (> 5 microns high) were quantified by morphometry. Deposition of [111In]oxine-labeled platelets was quantitatively determined per surface unit. In addition, prostaglandin I2 (PGI2) formation by the denuded aortic and iliac artery segment was determined. In group I, receiver rabbit pretreatment with isradipine exhibited decreased adhesion and aggregation of platelets, even when the donor rabbit was treated with solvent or ASA. In group II, concomitant treatment of donor animals with ASA and isradipine had no significant effect, whereas ASA isradipine treatment of receiver animals enhanced thrombogenicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Atherosclerotic lesions in humans--plaque stabilization and regression.

Although lowering of total- and LDL-cholesterol with different methods, like dietary restrictions mostly combined with lipid-lowering drugs (monotherapy or combined drug therapy) or changes in lifestyle (e.g., cessation from smoking) have demonstrated significant clinical benefits in a number of clinical trials, the magnitude of angiographically proven regression of atherosclerotic lesions is relatively small despite aggressive lipid-lowering regimens. A potentially important therapeutic target especially for limited indications includes the use of LDL-apheresis, where functional and later morphological regression occurs.

Arteriosclerosis↗