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Biomedical subjects

H Sinzinger

Publications and source records attributed to H Sinzinger.

At least 127 records · Page 7Linked to original sources
PubMed1998

Unusual imaging of varicose veins after radiolabeling of autologous low-density lipoproteins.

LDL-radiolabeling with various isotopes (123I, 125I, 131I, 111In, 99mTc and 67Ga, among others) has been used for imaging the arterial wall, monitoring the LDL-kinetics and in particular to assess vascular surface lining and foam cell content. From 286 patients studied with 111In-LDL scintigraphy, only 9 patients presented clinical varicosis. In 2 of these 9 patients a predominant imaging of varicose veins has been shown with scintigraphy, while in the other 7 patients no positive scintigraphic imaging could be detected. In vitro and in vivo perfusion experiments did not reveal an explanation for this unusual results. The reason for that positive LDL-uptake into varicose veins is unknown. These findings indicate that localized LDL-uptake has to be interpreted carefully in order to avoid potential false positive results.

Adult↗
PubMed1998

Levels of eicosanoids (6-oxo-PGF1 alpha and 8-epi-PGF2 alpha) in human and porcine lymphatics and lymph.

Prostaglandin (PG)I2 is the primary eicosanoid synthesized by human lymphatics and 8-epi-PGF2 alpha, an isoprostane formed during free radical catalyzed peroxidation, is the most potent stimulator of lymphatic contraction tested thus far. We now examine the respective concentrations in the lymphatic wall of both human and porcine lymphatics and lymph fluid using specific immunoassays. Although both compounds are detectable in the lymphatic wall and lymph fluid, PGI2- (via its main metabolite 6-oxo-PGF1 alpha) is greater in the lymphatic wall whereas 8-epi-PGF2 alpha dominates in lymph fluid. Because inflammation is associated with oxidative injury, which in turn stimulates release of isoprostane, eicosanoid derivatives may modulate lymphatic tone during acute tissue reaction.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Tea consumption, lipid metabolism, and atherosclerosis.

The use of tea is derived from the Far East and was introduced into Europe, where in some countries tea soon became a favorite drink. Tea accounts for about 43% of all caffeine consumption. Total world caffeine consumption in 1981 was estimated to be approximately 120,000 tons, equivalent to 70 mg a day for each human. There is evidence from in vitro and animal studies, as well as from human investigations, that tea and its main constituents can prevent atherosclerosis to a certain extent. Supplementing tea as beverage instead of coffee might react beneficially with other antiatherosclerotic strategies. Investigations on the hypolipidemic and antiatherosclerotic action of tea, and therefore flavonoid intake, are still in their infancy and further fundamental data from controlled trials are needed to evaluate possible positive effects of tea consumption to prevent or treat atherosclerosis. Brief information on the biological potential of caffeine and flavonoids, as well as on their possible beneficial effects on the atherosclerotic process is documented in this review.

Animals↗
PubMed1997

Hyperalphalipoproteinemia and prostaglandin I2 stability.

PGI2 is a powerful regulator of thromboresistance modulating the local platelet/vessel wall interaction. Beside the amount synthesised the availability of the biologically active compound depends on its half-life at the site of action. Plasmatic half-life of PGI2 is extremely shortened during severe infections, but also in acute myocardial infarction with extremely lowered levels of HDL-c and apoAI, the latter being described as a potential PGI2-stabilising factor. These conditions are characterised by an enhanced thrombophilic risk. This study investigated for the first time whether high levels of HDL-c (mean: 95 +/- 13 mg/dl) and apoAI (mean: 179 +/- 13 mg/dl) which have been shown epidemiologically to protect against coronary heart disease in turn might be associated with an increase in PGI2 half-life. Results were obtained from 31 healthy subjects with hyperalpha-LP as compared with 10 controls. The biological half-life of PGI2 (hyperalpha-LP: mean: 915 +/- 118 sec vs. controls: 714 +/- 70 sec; p = 0.001) was positively related to HDL-c (r = 0.8795, p < 0.001) and apoAI levels (r = 0.8025, p < 0.001). The partial correlation coefficient correcting for the association between HDL-c and apoAI levels was also significant (PGI2 to HDL-c: r = 0.6000, p < 0.001). These results suggest that the antiatherosclerotic properties of HDL might be at least partly due to an increase in PGI2 half-life.

Adolescent↗
PubMed1997

Effect of isradipine on in-vivo platelet function.

In animal studies calcium channel blockers (CCB's) and especially isradipine, a second generation dihydropyridine, interrupt the sequence of events culminating in the formation of atherosclerotic lesions. The effect of 4 weeks isradipine treatment (5mg daily) on blood pressure and in-vivo platelet function (measured with 111Indium-oxine labeled autologous platelets) were investigated in a randomized, double-blind and placebo controlled trial in 40 patients with mild to moderate hypertension and scintigraphically diagnosed active atherosclerotic lesions of the carotid arteries. The average supine systolic/diastolic blood pressure was significantly reduced at the end of the treatment period in the isradipine group (group 1; p < 0.0001) but remained unchanged in the placebo group (group P). The heart rate was not significantly altered in either group. There were no serious side effects. The platelet uptake ratio (PUR) measured over the atherosclerotic region of the carotid artery on 4 consecutive days before and after treatment decreased significantly in group I from 1.20 to 1.15 (within groups: p < 0.0001) but remained unchanged in group P. Platelet survival increased significantly in group I (mean 5.70 hours, lower quartile 4.50, upper quartile 4.50 hours, within groups: p < 0.0001) and remained unchanged in group P. Isradipine has a beneficial effect on in-vivo platelet function as evidenced by a decreased platelet deposition on vascular lesion sites and an associated prolonged platelet survival in patients with hypertension and active atherosclerotic lesions.

Adult↗
PubMed1997

The influence of isoprostanes on ADP-induced platelet aggregation and cyclic AMP-generation in human platelets.

Isoprostanes are eicosanoids that are non-enzymatic products of free radical catalyzed peroxidation of arachidonyl containing phospholipids (1). They are subsequently released from the site of generation as esters of phospholipid (bound) or through the action of phospholipase(s) A2 in free form (2). One F2-isoprostane whose formation is highly favored is 8-iso-PGF2 alpha which has been shown to be a potent pulmonary and renal vasoconstrictor (3,4). Actions of 8-iso-PGF2 alpha were demonstrated to be mediated through a receptor related to but probably distinct from the thromboxane (TXA2)/endoperoxide (PGH2) receptor (5). Although 8-epi-PGF2 alpha is a potent agonist of TXA2/PGH2 receptors in vascular smooth muscle, interestingly it acts primarily as an antagonist of TXA2/PGH2 receptors on both human and rat platelets (6). There is also evidence for the generation of D- and E-ring isoprostanes (7) and their receptor-mediated action on smooth muscle cells (8) and platelets (9). Recent reports support the hypothesis that E2-isoprostane receptors are distinct from TXA2/PGH2 receptors, suggesting at least different subtypes, one of these specifically recognizing E2-isoprostanes (9). Isoprostanes have been suggested to be useful markers for oxidant injury. For example, F2-isoprostanes were significantly elevated in plasma of rats during reperfusion after hepatic ischemia (10) and in patients with hepatorenal syndrome (11). It has been suggested that the release of F2-isoprostanes from oxidized LDL in macrophages could be a contributory factor in the development of atherosclerosis and at sites of inflammation, locally elevated levels of isoprostanes could contribute to blood cell activation. In this study we investigate possible pro- or antiaggregatory properties of various F- and E-type isoprostanes on human platelets.

Adenosine Diphosphate↗
PubMed1997

Antimitotic actions of vasodilatory prostaglandins--clinical aspects.

A variety of in-vitro antiatherosclerotic actions, among them those on vascular smooth muscle cells (mitotic activity, proliferation, extracellular matrix production), have been identified especially for PGE1 and PGI2, and proven in experimental animals. Ex-vivo data in humans are not yet available. We examined the effect of PGE1-, PGI2- and iloprost therapy of various duration (1-4 weeks) on smooth muscle cells (mitosis, proliferation, prostaglandin formation from exogenous and endogenous substrate) derived from vascular surgery samples. In-vivo PG-therapy decreases [3H]-thymidine incorporation as well as [35]S- and [14C]-proline uptake. These effects are dependent on the duration of treatment, PGE1 being trendwise more effective. Arachidonic acid conversion to PGI2 is significantly enhanced in activated smooth muscle cells of the plaque, both in the intima as well as in the media. Due to the activation of the gene for COX-2, the actual synthesis of PGI2 as well as the conversion rate to 6-oxo-PGF1 alpha are increased in activated smooth muscle cells, an effect being abolished by the PG's administered. It can thus be concluded that PG-therapy for advanced atherosclerosis seems to affect vascular smooth muscle cells beneficially, decreasing mitotic and proliferative activity as well as collagen and glycosaminoglycan synthesis. The somewhat less pronounced effect for PGI2 and iloprost could be explained by desensitization at the receptor level as preliminary findings suggest. This could become even more relevant if a long-term administrable stable (oral) analogue becomes available for routine therapy.

Adult↗
PubMed1997

Monitoring of the biodistribution and biokinetics of dysprosium-165 ferric hydroxide with a shadow-shield whole-body counter.

Radiation synovectomy is indicated when conventional pharmacological treatment of chronic synovitis has proved insufficient. In these cases dysprosium-165 ferric hydroxide (DFH) has been demonstrated to be clinically effective. After application of the agent, blood activity measurements and monitoring of activity distribution by gamma camera imaging over the local lymph nodes and the liver are commonly performed for control of possible leakage. In addition, we have used a shadow-shield whole-body counter with a profile facility to evaluate the biokinetics and biodistribution of 165Dy-DFH. Fifteen intra-articular injections were performed in 13 patients who received a median activity of 6.8 GBq (range 0.5-9.9 GBq) 165Dy-DFH. Activity profiles were obtained with the whole-body counter 2, 4 and 6 h after injection of 165Dy-DFH. The doses to non-target organs were calculated using the software MIRDOSE 3. In 10 of 15 treatments, absence of any leakage could be demonstrated. The effect of scattered rays could be observed in 14 measurements. In three patients small amounts of activity could be detected in the urinary bladder and in three patients activity was detected in the local inguinal lymph nodes, while no leakage could be detected by camera imaging. In these cases the individual doses to the bladder were 15 Gy, 65 mGy and 50 mGy, and those to the lymph nodes, 0.54 Gy, 0.89 Gy and 2.41 Gy. The whole-body counter also enabled the monitoring of activity profiles related to more complex pathological structures. In conclusion, using a whole-body counter activity leakage could be detected with much higher sensitivity than by using a gamma camera. The biodistribution of 165Dy-DFH could be determined, and leakage could be localised and related to organs. These results encourage the use of a whole-body counter to identify the site and extent of activity leakage.

Adult↗
PubMed1997

Prostaglandin E1 decreases human arterial accumulation of radiolabeled apo B-containing lipoproteins in vivo.

OBJECTIVE: An increased apo B-containing lipoprotein influx and cholesterol ester accumulation in arteries are well-known events in human atherogenesis. In vitro and experimental animal studies have provided evidence of a beneficial effect of PGE1 on both vascular apo B-containing lipoprotein accumulation and cholesterol ester content. METHODS: We examined the effect of PGE1 (administered via an intravenous portable infusion pump at a rate of 5 ng PGE1 kg-1.min-1 for 5 days a week, 6 h daily, over a total of 5 weeks) in ten patients (eight males, two females) on 123I-apo B-containing lipoprotein accumulation into the large arteries in vivo. Apo B-containing lipoprotein isolation was carried out by immunoaffinity chromatography and radiolabeling with the iodine monochloride method. 123I-apo B-containing lipoprotein accumulation was imaged and quantified by means of special computer software before and after 5 weeks of PGE1 therapy. RESULTS: PGE1 led to a significant decrease in maximal arterial apo B-containing lipoprotein retention. The mean decrease in the carotid and femoral arteries in type I lesions amounted to between 16.9% and 30.4%, and in type II lesions between 22.4% and 30.7%, 20 h after injection of radiolabeled apo B-containing lipoprotein. The type of arterial apo B-containing lipoprotein kinetic curves, however, remained unchanged. CONCLUSION: These findings indicate that PGE1 decreases the apo B-containing lipoprotein influx in the large arteries and the vascular cholesterol content, suggesting that PGE1 may lead to regression of lipid-rich lesions in human in vivo.

Alprostadil↗
PubMed1997

Effect of prostaglandin E1 infusion in severe chronic heart failure.

Prostaglandin E1 (PGE1, alprostadil) is a potent vasodilating agent that is frequently used to resolve cardiogenic pulmonary hypertension. To investigate the effect of PGE1 in refractory chronic heart failure in a double-blind trial, twenty patients (17 men, 3 women, 58 +/- 2 years, cardiac index < or = 2.5 l/min/m2, pulmonary capillary wedge pressure > or = 20 mmHg), who were in NYHA functional class IV on optimized treatment with ACE inhibitors and furosemide were infused with 30 ng/kg/min PGE1 or placebo through 48 hours. All patients received a concomitant therapy with standardized catecholamine infusions which were given 24 hours in advance and were continued throughout the study. There was no difference in baseline values between the randomized groups before PGE1 or placebo was added. PGE1 resulted in decrements in pulmonary artery pressure (from 37 +/- 4 to 30 +/- 4 mmHg; p < 0.01), pulmonary capillary wedge pressure (from 26 +/- 4 to 19 +/- 3 mmHg p < 0.001) systemic vascular resistance index (from 2048 +/- 213 to 1506 +/- 13 dyn.sec/cm5.m2, p < 0.05) and in increments in cardiac index and stroke volume index (from 2.2 +/- 0.1 to 2.8 +/- 0.2 l/min.m2; p < 0.05 and from 23 +/- 2 to 28 +/- 2 l/m2; p < 0.05, respectively). Moreover, creatinine clearance increased (p < 0.05). Placebo infusions did not result in any hemodynamic or renal effect. Between groups percentage hemodynamic changes differed with respect to pulmonary artery pressure (p < 0.01), cardiac index (p < 0.05), stroke volume index (p < 0.05) and pulmonary vascular resistance index (p < 0.05). It is concluded that intravenous infusions with PGE1 may add further substantial benefit to the hemodynamic state in refractory heart failure patients who are already stabilized on i.v. inotropic support with catecholamines.

Aged↗
PubMed1997

PGE1-induced arterial thromboresistance is a vascular property as identified by cross-perfusion technique.

Prostaglandin (PG) E1 has been shown to improve thromboresistance. This experiment was designed to examine whether an effect on the arterial wall or the platelets is responsible for this phenomenon. Using a cross-perfusion model, the aortic and iliac artery endothelium of rabbits was removed by a balloon catheter before being perfused with blood of donor rabbits. Donor and/or receiver animals were treated with 20 microg PGE1 or vehicle (cyclodextrin) intravenously daily for 1 week. After the last administration of PGE1 or its vehicle, the animals were killed and native blood from a donor rabbit was recirculated (30 ml/min) via a deendothelialized segment of a receiver rabbit. The contact (C) and spread (S) platelets as well as the denuded surface covered with platelet aggregates (> 5 microm in height) were quantified by morphometry. Deposition of (111)In-oxine labeled autologous platelets was quantitatively determined per surface unit. In addition, PGI(2)- and TXB2-formation by the denuded aortic and iliac artery segments was determined. Pretreatment of receiver rabbits with PGE1 resulted in morphometrically assessed decreased platelet adhesion and aggregation, even when the donor rabbit was vehicle-treated. A vehicle-treated receiver rabbit, in contrast, shows platelet deposition comparable to controls, even if the donor rabbit was PGE1-pretreated. Treatment of donor animals with PGE1 did not result in a reduction in thrombogenicity. The beneficial in vivo PGE1 action of decreased arterial thrombogenicity is thus mediated by an effect on the vascular wall rather than on circulating platelets.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Chloroquine minimizes sampling artefacts for radioimmunological determination of thromboxane B2 in plasma.

Chloroquine is known to inhibit platelet activation by various mechanisms including arachidonic acid liberation from membrane phospholipids. We therefore examined the influence of chloroquine in addition to the conventional EDTA/acetylsalicylic acid cocktail on thromboxane B2-plasma values. In 11 healthy volunteers the influence of venous occlusion, needle diameter and EDTA (+ acetylsalicylic acid + chloroquine) was examined. In 27 healthy adults, 51 patients with clinically manifested coronary heart disease as well as in 31 patients with peripheral vascular disease parallel samples drawn in the presence of chloroquine showed lower thromboxane B2 in all these three groups of patients, especially in conditions associated with platelet activation and high thromboxane B2-values. These findings suggest that the routine addition of 10 mM chloroquine to the conventional stabilization cocktail can strongly be recommended.

Adult↗