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Biomedical subjects

H Sinzinger

Publications and source records attributed to H Sinzinger.

At least 109 records · Page 6Linked to original sources
PubMed1999

Semotiadil, a new calcium antagonist, is a very potent inhibitor of LDL-oxidation.

The influence of semotiadil, a novel benzothiazine calcium antagonist on in-vitro copper-, 2,2àzo-bis-(2,4 dimethylvaleronitrile)[AMVN]-, and 2,2àzo-bis-(2-amidinopropane) [AAPH]-induced low-density lipoprotein (LDL) oxidation was assessed. The following parameters were measured: lag-time of oxidation, maximal rate of oxidation, dienes formed through continuous monitoring of developing conjugated dienes, thiobarbituric acid reactive substances, isoprostane(8-iso-PGF2alpha)-generation and relative electrophoretic mobility. The effect was compared with nifedipine, amlodipine and diltiazem. Besides the influence on isoprostane (8-iso-PGF2alpha)-generation where nifedipine was equipotent with semotiadil at 10(-3) M, semotiadil demonstrated a strong and significant effect in attenuating the indicated indices of LDL-oxidation, in particular, dose-dependently (10(-3) M to 10(-7) M). These results indicate that semotiadil may have the strongest antioxidant activity on LDL among the calcium antagonists examined.

Adult↗
PubMed1999

111In-labelled platelets for assessment of thrombogenicity of new haemodialysis vascular access.

Using platelet scintigraphy to evaluate early thrombogenicity, we examined 39 new vascular accesses 4 weeks and 3 months after surgery. We found a significant association between platelet deposition and Doppler flow (P < 0.01) and blood pressure (P < 0.01). Compared with arteriovenous fistulae, prosthetic grafts showed significantly higher platelet uptake (after 4 h: 2.4 +/- 1.1 vs 1.2 +/- 1.1 eU, P < 0.05; after 24 h: 2.1 +/- 1.0 vs 0.6 +/- 0.8 eU, P < 0.01) and a higher Doppler flow (1184 +/- 202 vs 609 +/- 342 ml.min-1, P < 0.001). In 8 of 39 accesses, a thrombosis occurred. Accumulation of activity was not related to shunt thrombosis (specificity 61%, sensitivity 71%). We conclude that 111In-platelet scintigraphy is not suitable for the early detection of shunt thrombosis or for identifying patients at risk.

Adult↗
PubMed1999

Influence of etoposide on the retention of radiolabeled low-density lipoprotein in the arterial wall.

BACKGROUND: Cardiovascular toxicity of chemotherapy for testicular cancer is a matter of discussion, since highly efficient agents can achieve cure of the disease, even in the metastasized setting. Acute ischemic events during the treatment period and a persistently elevated serum cholesterol thereafter are observations of particular concern in these patients, and the underlying basic mechanisms are unknown to date. OBJECTIVE: To evaluate etoposide, which is part of the standard treatment for testicular cancer, as a potential cause of atherogenesis in an experimental model. SETTING: Aortic 125I-labeled low-density lipoprotein retention was studied in 72 cholesterol-fed rabbits under etoposide treatment and was quantified according to the morphologically assessed type of surface lining. Aortic cholesterol content was determined both by Sudan III staining and quantitatively by a biochemical assay. RESULTS: A reduced uptake of 125I-labeled low-density lipoprotein in the arterial wall was observed in the etoposide-treated animals, which resulted in a size reduction of sudanophilic areas and cholesterol content. Whereas the breakdown of 125I-labeled low-density lipoprotein in the liver was not significantly enhanced, the plasma decay of 125I-labeled low-density lipoprotein was faster and serum cholesterol was lower in the etoposide group than in controls. CONCLUSION: Unexpectedly, we found an improvement of arterial wall lipid metabolism under etoposide treatment and can thus exclude this substance as a promoter of atherogenesis in this model.

Animals↗
PubMed1999

Influence of radiation synovectomy on articular cartilage, synovial thickness and enhancement as evidenced by MRI in patients with chronic synovitis.

UNLABELLED: Radiation synovectomy is a safe and effective treatment for chronic synovitis that is refractory to the repetitive, intra-articular application of glucocorticosteroids in patients with rheumatoid or seronegative arthritis. Short-term and long-term effects of radiation synovectomy on articular cartilage, synovial enhancement and thickness were assessed in a prospective, clinical trial by MRI. METHODS: Thirteen patients (mean age 39+/-13 y) were treated with a median activity of 8.4 GBq 165Dy ferric hydroxide, a radionuclide with favorable physical properties and a well-documented clinical safety and efficacy profile. MRI was performed on a 1.5-T MR unit using a circular polarized knee coil. RESULTS: After a mean observation period of 13 mo, a marked reduction in synovial enhancement was observed in 10 patients. The mean reduction in baseline synovial thickness (mean 7.6+/-3.0 mm) was 24% (P = 0.03) at 1 wk and 42% (P = 0.01) about 1 y after treatment, respectively. Clinically, 9 of 13 patients (69%) exhibited persistent response to radiation synovectomy. The local clinical score, as defined by the reduction in pain, pannus, joint effusion and by the increase in the range of motion, improved significantly (P = 0.01), from a median of 7 (range 4-10) to a median of 2 (range 0-9). One year after treatment, changes in the local clinical score were related to the decrease in synovial enhancement in MRI (r = 0.7, P = 0.008, n = 12). There were no persistent adverse effects, nor was there evidence for any severe radiation-induced damage to the articular cartilage. On later follow-up images, the structure of the articular cartilage remained unaltered in all but 3 patients, who had new, superficial erosions most likely attributed to an active disease with persistence of inflammation. CONCLUSION: This study suggests that radiation synovectomy with 165Dy-ferric hydroxide is effective in terms of reducing chronic synovitis without causing detectable harm to the articular cartilage, as shown by MRI.

Adult↗
PubMed1999

Endothelial dysfunction, atherosclerosis and diabetes.

The prevalence of early and accelerated development of atherosclerosis associated with high morbidity and mortality is markedly increased among individuals with diabetes and hypertension. Although the link between diabetes and vascular disease is not fully understood, loss of the modulatory role of the endothelium could be implicated in the pathogenesis of diabetic vascular complications. Diabetes-associated pathophysiologic conditions in the endothelium are modifications of lipoproteins, formation of advanced glycation end-products and circulating lipoprotein immune complexes, alteration of the nitric oxide pathway, and elevated levels of homocysteine. The main goals in restoration of endothelial function are optimal glycemic control, lipid lowering, cessation of smoking, normalization of elevated blood pressure, improvement of the NO-status, antioxidants for scavenging free oxygen radicals, normalization of homocysteine levels, antagonizing the hyperinsulinaemia, and regulation of rheology, respectively haemostasis to physiological levels. There is abundant evidence that some pharmacological agents exert direct beneficial effects on endothelium, suggesting that at least part of their therapeutic action is associated with improvement in endothelial dysfunction. A number of new findings about endothelial dysfunction may have potential clinical relevance.

Arteriosclerosis↗
PubMed1998

Accumulation of platelets as a key mechanism of human erection.

In this study, the role of platelets in the human erectile response was assessed. Twenty patients with erectile dysfunction were studied by means of (111)In-oxine-platelets and blood pool imaging using 99mTc. Seventeen patients received intracavernously prostaglandin E1, and three patients received papaverine together with phentolamine. In patients who responded with erection, an increase by between 16 to 137% platelets/ml and a rapid platelet accumulation in the penis during the initial phase of erection were observed. In patients without erection, no change in local platelet concentration occurred. It is likely that platelets play a major role in human erection, probably by temporary activation, thereby regulating venous outflow.

Adult↗
PubMed1998

Prostaglandins as biochemical markers of radiation injury to the salivary glands after iodine-131 therapy?

Because salivary glands, as well as thyroid tissue, are able to concentrate radioiodine, the treatment of thyroid diseases with iodine-131 may have secondary effects on salivary gland function which seriously impair the quality of life. Such effects include sialoadenitis and xerostomia. Salivary secretion is stimulated by prostaglandins (PGs). In this study we evaluate whether 131I therapy influences the levels of PGs in saliva. Patients who had previously received 131I for treatment of hyperthyroidism or differentiated thyroid cancer and healthy volunteers were studied. Levels of PGs [6-oxo-PGF1 alpha, bicyclo-PGEm, thromboxane B2 (TXB2), PGF2 alpha] in unstimulated saliva were measured using enzyme immunoassay. Significantly lower levels of 6-oxo-PGF1 alpha, bicyclo-PGEm and PGF2 alpha and higher levels of TXB2 were found in the group of patients in comparison with the controls. Differences between patients and controls were more pronounced in smokers. This study demonstrates that salivary gland uptake of 131I significantly affects PG levels in saliva.

Adult↗
PubMed1998

Adsorption of technetium-99m tetrofosmin and technetium-99m furifosmin on plastic syringes.

Some groups have reported that adsorption of radiopharmaceuticals on disposable plastic syringes can reach levels of almost 50%. This high loss of radioactivity stimulated us to carry out similar studies. Our measurements were done in combination with patient studies. Therefore, we used 2-ml syringes, all of the same brand. The radioactivity in the syringe was measured immediately before and after injection. a total of 500-600 MBq technetium-99m labelled tetrofosmin or technetium-99m furifosmin was administered to 48 patients using four different injection techniques (n = 6 for each technique with each tracer): with needles, 1 min blood incubation at 22 degrees C, 10 or 30 min after preparation of the tracer; with butterflies, 1 min blood incubation at 22 degrees C, 10 or 30 min after preparation of the tracer. Neither in syringes nor in needles or butterflies did more than 7% of the initial radioactivity remain. The entire residual activity in syringe plus needle or syringe plus butterfly together never exceeded the 9% limit. Furthermore, in a pilot study we measured the remaining radioactivity in the vial; here, too, we found no more than 14% of total radioactivity. These findings indicate that total retention of radioactivity during elution and application of 99mTc-tetrofosmin and 99mTc-furifosmin with material used in our setting does not approach relevant amounts.

Adsorption↗
PubMed1998

Do E-series prostaglandins and their metabolites influence oxidation of native and glycated low-density lipoproteins?

Oxidation of lipoproteins, and, in particular, low-density lipoproteins (LDL), has been shown to play a significant role in the pathogenesis of atherosclerosis. Oxidized LDL are endocytosed via scavenger receptors to form lipid-laden foam cells. The non-enzymatic reaction of glucose with proteins and lipoproteins results in a modified LDL involved in the pathogenesis of late complications in diabetes mellitus. In the present paper, the influence of various E-series prostaglandins (PGE1; 13,14-dihydro PGE1; 13,14-dihydro 15-keto PGE1; and PGE2) on oxidation of native and glycated LDL was investigated. The effect of these agents in the concentration range from 1 pg/mL to 1.6 micrograms/mL on copper-induced oxidation of native and glycated LDL was tested. The concentration of each agent causing the maximal effect on oxidation of native LDL, as measured by the formation of thiobarbituric acid-reacting substances, was chosen to estimate the effect on 2, 4, 8, and 24 h oxidation of glycated LDL. The study was performed with LDL isolated by sequential ultracentrifugation from normolipidemic individuals. LDL (0.25 mg protein/mL) was oxidatively modified with 5 microM CuSO4. The glycosylation of LDL was performed by incubation of LDL with 500 mM glucose for varying periods of time ranging from 10 to 31 days. Our results show that only 13,14-dihydro PGE1 significantly inhibits copper-induced oxidation of native LDL, while the other examined E-series prostaglandins in vitro are ineffective as reducing agents in LDL-oxidation.

Adult↗
PubMed1998

Effects of prostaglandin E1 metabolites on the induction of arterial thromboresistance.

Prostaglandin (PG) E1 has been shown to induce arterial thromboresistance in experimental animals and in man. It is known to be degraded in vivo to metabolites which have comparable (13,14-dihydro-PGE1) or no (15-keto-PGE1, 15-keto-13,14-dihydro-PGE1) biological activity. It was the goal of this study to examine whether 13,14-dihydro-PGE1 and its derivatives might share biological activity in rendering the arterial wall less thrombogenic. Using a cross-perfusion technique the aorta and iliac artery surface were exposed to a donor rabbits' blood. We examined the intact endothelial lining and a surface which had been deendothelialized before by means of a Fogarty catheter. Donor animals and/or receiver animals were treated daily for 1 week with 13,14-dihydro-PGE1, PGE1, 15-keto-PGE1, 15-keto-13,14-dihydro-PGE1, or the vehicle only, respectively. From the group of the receiver animals, a subgroup of 6 animals each was treated for the same period of time with either 13,14-dihydro-PGE1, PGE1, 15-keto-PGE1, 15-keto-13,14-dihydro-PGE1, or the vehicle. Immediately after the last administration of the respective PG or solvent, native blood from a donor rabbit was circulated [30 mL/min. under in vivo flow conditions (60 Hz)] over an arterial segment of a receiver animal. Deposition of 111Indium-oxine labeled autologous platelets per surface unit was quantitatively assessed. In vitro perfusion data were morphometrically analysed. In animals pretreated with 13,14-dihydro-PGE1 the thromboresistance was almost comparable to that achieved with PGE1. In contrast, pretreatment of the donor animals (platelet) had only minor effects on the thromboresistance. The other compounds showed no effects. In vitro perfusion of human saphenous vein segments revealed PGE1 and 13,14-dihydro-PGE1 again to be of comparable potency, while 15-keto-PGE1 and 15-keto-13,14-dihydro-PGE1 were only active at concentrations being several orders of magnitude higher. Not only PGE1 but also its in vivo formed metabolite PGE0 may play an important role in inducing improvement of haemostatic balance via the vascular wall rather than the platelets. The other metabolites, however, are unlikely to exhibit an effect at biologically relevant concentrations.

Alprostadil↗
PubMed1998

Isradipine lowers human arterial low density lipoprotein retention in vivo.

During the recent past it has been discussed that calcium antagonists may exert antiatherosclerotic actions at the vessel wall. Apolipoprotein B containing lipoproteins were isolated by immunoaffinity chromatography and radiolabeled with 123-iodine. The effect of 2 x 2.5 mg isradipine on the low density lipoproteins (LDL) entry into the carotid and femoral arteries of 12 hypertensive patients with primary hyperlipoproteinemia (total cholesterol >6.5 mmol/l [250 mg/dL) was examined. Cholesterol -1.7% (P< 0.05 664), high density lipoprotein (HDL) cholesterol +4.5% (P< 0.01 123), and LDL cholesterol -1% (P< 0.01 563) did not change, nor did any of the safety parameters. The types of entry kinetics reflecting vascular surface lining did not change while the LDL retention 20 h after tracer application was depressed by up to 23.5%. The data were comparable in the carotid and femoral artery segments, the significance level ranging up to 0.0009. These results indicate a decreased LDL retention in the arterial wall of hypertensive patients induced by isradipine. The clinical implications of the findings ought to be pursued in properly designed clinical trials.

Adult↗
PubMed1998

Alteration of rat cerebral microvascular eicosanoid formation by isradipine, a calcium channel blocker.

We studied the influence of the calcium channel blocker isradipine on cerebral microvascular and aortic eicosanoid synthesis. The rat cerebral microvascular eicosanoid formation was assessed by means of bioassay, radioimmunoassay and radio thin layer chromatography from endogenous as well as from exogenous (20:4) radiolabelled substrate. The in vitro as well as the in vivo (0.3 mg/kg/day for 1 week) effect of isradipine was examined. Isradipine increased significantly (P < 0.01) both conversion to and formation of PGI2 and its derivative 6-oxo-PGF1alpha respectively, as well as PGD2-production, while TXB2-synthesis was diminished. The conversion to the other metabolites was not affected to a significant extent. These findings indicate that isradipine enhances PGI2-generation in aorta and cerebral microvessels from both exogenous and endogenous substrate and PGD2 from endogenous substrate, a phenomenon shown to underlie the antiatherosclerotic actions of this calcium channel blocker.

6-Ketoprostaglandin F1 alpha↗