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Biomedical subjects

H Sinzinger

Publications and source records attributed to H Sinzinger.

At least 307 records · Page 17Linked to original sources
PubMed1989

131I-metaiodobenzylguanidine (mIBG) for bronchial oat cell cancer and melanoma detection?

The neuroendocrine features of bronchial oat cell carcinoma and melanoma indicate the possibility of positive imaging by means of radiolabelled metaiodobenzylguanidine. However, only four out of seven patients with bronchial oat cell carcinoma and three out of seven with melanoma were correctly diagnosed. Only false negative and no false positive results were obtained. The findings demonstrate a limited diagnostic value of the tracer in the tumor types examined.

3-Iodobenzylguanidine↗
PubMed1989

Enhancement of human dental cyst PGI2 formation by platelet derived growth factor and its role in cyst growth and bone resorption.

Various prostaglandins, particularly PGE2 and PGI2, appear to play a major role in osteolytic processes. Radiochromatographic studies have demonstrated that 6-oxo-PGF1-alpha is a major product of exogenously added arachidonic acid in human dental cysts. As platelets may also act as inflammatory cells, platelet-derived growth factor might also have a PGI2-stimulating influence in such cysts. Eleven human dental cysts were examined by a radioimmunoassay and bioassay which can show PGI2 synthesis in human dental cysts without addition of PDGF. Incremental PDGF addition caused a highly significant increase in the rate of PGI2 synthesis. PGDF thus stimulates PGI2 synthesis in chronic inflammatory processes in vitro and may thereby elicit or accelerate osteolysis.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Humoral regulation during cold-induced coronary arterial spasm.

Previous attempts to define the etiology of coronary arterial spasm have been focused on mechanisms such as autonomic nervous dysfunction and/or enhanced platelet activation. In the present study, humoral regulation was investigated in patients with vasospastic angina and scintigraphically documented transient myocardial perfusion abnormalities after a peripheral cold pressor test. Serial changes in angiotensin II, epi- and norepinephrine as well as thromboxane B2 (the stable derivate of thromboxane A2), and malondialdehyde were determined at baseline (I), immediately after 5 minutes cold water hand immersion (II), and following 10 minutes recovery (III). Angiotensin II and epinephrine remained unchanged during observation (I vs II, II vs III: P = NS). Norepinephrine was elevated after cold (I vs II: P less than 0.001) and normalized after 10 minutes (I vs III: P = ns). Thromboxane B2 and malondialdehyde increased continuously (I vs III: P less than 0.05 and I vs III: P less than 0.002, respectively). Further radiothin-layer chromatography results indicate an activation of platelet function during myocardial ischemia. Our results do not establish a cause-effect relationship but, together with other evidence, they may suggest that thromboxane A2 is unlikely to be the cause of spasm. It might, however, play an important role in the maintenance of vasoconstriction.

Angiotensin II↗
PubMed1989

The optimal processing of plasma samples for the determination of bicyclo-PGE in patients with malignant maxillofacial tumors.

Prostaglandins (PGs) have been shown to be increased in several tumor tissues. PGE2 and PGF1-alpha Radioimmunoassays (RIAs) have been widely used for quantitative PG-measurements in cancer patients. Our results indicate that optimal processing of plasma samples for the determination of bicyclo-PGE2 is of the highest importance in order to get reproducible results. Therefore it is necessary to fulfill the following requirements: 1. 30 minutes rest before sampling; 2. Avoid venous occlusion; 3. Use constant needle diameter; 4. Precooled anticoagulant; 5. Addition of a cyclooxygenase inhibitor is necessary; 6. Control of processing temperature; 7. Storage at -70 degrees C less than -20 degrees C; 8. Control of storage time; 9. The samples have to be examined after thawing once; 10. Only blood samples processed under the above discovered optimal conditions are of clinical relevance; 11. An international standardization for the processing of plasma samples seems to be necessary considering all these requirements; 12. In 41 patients with maxillo-facial carcinomas the PG-value was significantly higher than in the controls; 13. A RIA-evaluation methodologically properly done may be used as an additional aid for clinical monitoring of the patients.

Adult↗
PubMed1989

Prostacyclin I2 (PGI2) increases left ventricular ejection fraction (LVEF).

In order to evaluate the effect of PGI2 on left ventricular ejection fraction (LVEF) an intravenous infusion in 10 patients (3 males, 7 females; 36 to 63 years) with an impaired LVEF (34.7 +/- 14.8%) was performed. LVEF was determined by means of 99mTc-pertechnetate radionuclide ventriculography. An increase of LVEF to 36.2 +/- 13.5% during administration of PGI2 at a rate of 1 ng/kg/min for 15 min and to 43.8 +/- 15.8% during a rate of 5 ng/kg/min (p less than 0.01) for an additional 15 min was observed. Analyzing the data in more detail in 6 patients, an improvement in LVEF became obvious during the administration of 1 ng/kg/min (108, 109, 116, 118, 121, and 123% of pre-infusion value, respectively). In 5 out of these 6 patients a dose-increment to 5 ng/kg/min further increased LVEF (139, 179, 187, 148, and 128% of pre-infusion value, respectively). In contrast, in the other 4 patients no response of LVEF to PGI2 at a rate of 1 ng/kg/min could be observed. However, in 2 out of these 4 patients LVEF increased during the administration of 5 ng/kg/min (111 and 117% of pre-infusion value). Individual changes in hemodynamic parameters showed no correlation to the improvement seen in LVEF in response to PGI2. It is concluded that PGI2 may exert beneficial effects on LVEF, and might be used in certain clinical conditions, such as before heart transplantation, to achieve a temporary improvement in LVEF.

Adult↗
PubMed1989

Beneficial effect of long-term PGE1-treatment in left ventricular heart failure.

Five male patients aged 34-47 years with congestive heart failure showed an improvement of left ventricular ejection fraction (LVEF) at rather low PGE1-doses (10-30 ng/kg/min) without affecting blood pressure or heart rate. LVEF was estimated by means of radionuclide ventriculography (RNV) prior to and during i.v.-infusion of PGE1 at increasing dose rates (10-100 ng/kg/min). Therefore, we administered to these responders PGE1 at a rate of 20 ng/kg/min i.v. continuously on a long-term basis by means of a portable infusion pump. Until up to 4 months the remarkable benefit in LVEF induced by PGE1 was still present to a comparable extent in all the patients. No rebound desensitization phenomenon occurred either on platelet activity or on LVEF. PGE1, via a more practical route of application or by a stable analogue, may be a promising therapy at this stage of cardiomyopathy (CMP).

Adult↗
PubMed1989

Decrease of the prostaglandin I2 binding capacity in thyroids from patients with Graves' disease.

Properties of prostaglandin (PG) I2-binding sites in human thyroids from euthyroid and thyrotoxic patients were investigated. The specific binding of 3H-iloprost (ZK 36374, a chemically stable PGI2-analogue) to normal thyroids approached saturation at a concentration of more than 150 nmoles/L and could be displaced most effectively by unlabeled iloprost (concentration causing the half maximal inhibition, IC-50 = 5.9 +/- 2.9 mumoles/L) and PGI2 (IC-50 = 9.8 +/- 3.1 mumoles/L) and less effectively by unlabeled PGF2 alpha (IC-50 = 847.9 +/- 123.8 mumoles/L) at 4 degrees C. The Scatchard analysis clearly indicated heterogeneity revealing the presence of 0.65 +/- 0.18 pmoles/mg protein at the high-affinity binding sites (equilibrium dissociation constant, Kd = 18.2 +/- 9.1 nmoles/L) and 5.35 +/- 1.6 pmoles/mg protein at the low-affinity binding sites (Kd = 151.3 +/- 43.1 nmoles/L). In contrast, in diffuse colloid struma derived from patients with Graves' disease a single class of binding sites with an apparent binding capacity of 0.18 +/- 0.05 pmoles/mg protein (Kd = 70.4 +/- 27.3 nmoles/L) was indicated. However, in diffuse colloid struma derived from euthyroid patients no difference in the number of binding sites and binding affinity of 3H-iloprost was noted compared to normal thyroids. The data provide evidence for the presence of specific PGI2-binding sites in the human thyroid gland and demonstrate a significant decrease of the receptor density in patients with Graves' disease. It is suggested, that PGI2 has an important role in the regulation of human thyroid function.

Binding Sites↗
PubMed1989

Glucocorticoid-treatment does not influence the synthesis of thromboxane B2 and bicyclo-PGE2 in humans.

It has been reported that the anti-inflammatory action of glucocorticoids is due to the inhibition of phospholipases. Consequently, after high-dose steroid treatment in humans a decrease in cyclooxygenase products should be expected. In 15 patients (10 males, 5 females, 29-62 y) undergoing 6-methyl-prednisolone-treatment (40-80 mg daily) for various clinical reasons and in 5 healthy volunteers (4 male, 1 female, 28-37 y) receiving 500 mg 6-methyl-prednisolone daily for 3 days plasma- and serum-thromboxane B2 (TXB2), as well as bicyclo-prostaglandin E2 (bicyclo-PGE2) were monitored over 3 weeks. In the entire follow-up period, however, no significant change in either serum- or plasma-TXB2 or bicyclo-PGE2 could be measured in either, patients and volunteers, under glucocorticoid-treatment. These findings indicate that even high-dose glucocorticoid-treatment does not affect the serum- and plasma-metabolites of the eicosanoids examined. It is concluded that in humans a significant inhibition of phospholipases by glucocorticoids and subsequently reduced formation of cyclooxygenase products seems to be rather unlikely.

Adult↗
PubMed1989

Effects of taprostene, a chemically stable prostacyclin analogue, in patients with ischaemic peripheral vascular disease: a placebo controlled double-blind trial.

Thirty patients with ischaemic peripheral vascular disease and intermittent claudication were randomly allocated to receive either placebo or taprostene, a chemically stable prostacyclin analogue, intravenously at a rate of 25 ng/kg/min for 6 hours daily on 5 consecutive days. Taprostene produced a significant (p less than 0.05) increase in absolute walking time compared to placebo on one day after infusion and at 1, 4 and 8 weeks (14% vs 2.8%) later. Taprostene also produced a significant (p less than 0.05) increase in the pain-free walking time compared to placebo in the follow-up period (8 weeks after infusion: 23% vs 3.8%). During the infusion period systolic and diastolic blood pressure decreased (p less than 0.05) and heart rate was accelerated (p less than 0.05) in the taprostene treated group whereas no change was monitored in the placebo group. The ankle/brachial Doppler index was unaffected by taprostene. The platelet half-life was significantly (p less than 0.05) prolonged following taprostene-infusion (72.6 +/- 9.35 vs 77.9 +/- 7.44 hours). However, no change on platelet half-life was found in the placebo group (p less than 0.05). Various measures of platelet function parameters followed in vitro (ADP-induced aggregation, platelet sensitivity to PGI2, PGE1, PGD1 and taprostene, concentrations of platelet factor 4 and beta-thromboglobulin) showed no change with taprostene. Measures of circulating platelet aggregates and endothelial cells count showed no changes during the 2 months follow-up period too. It is assumed that taprostene may be of clinical benefit in patients with ischaemic peripheral vascular disease. However, future investigations have to be carried out to assess the optimal dose regime.

Alprostadil↗
PubMed1989

Human hepatocellular cancers show decreased prostaglandin E1 binding capacity.

Specific binding of 3H-PGE1 to plasma membranes prepared from normal human hepatic tissue in the presence of Mg2+ reached saturation at concentrations greater than 50 nM, and could be displaced in the rank-order PGE1 greater than PGE2 greater than PGI2 greater than PGD2 greater than PGF2 alpha at 4 degrees C. Plasma membranes prepared from normal human hepatic tissue showed a high-affinity 3H-PGE1-binding capacity of 51.3 +/- 19.2 fmol mg-1 plasma membrane protein with an equilibrium dissociation constant of 3.8 +/- 1.9 nM, and a low-affinity 3H-PGE1-binding capacity of 104.2 +/- 17.3 fmol mg-1 protein with an equilibrium dissociation constant of 13.9 +/- 2.7 nM. Plasma membranes prepared from hepatocellular cancer tissue revealed a single class of binding sites with an apparent binding capacity of 38.4 +/- 17.3 fmol mg-1 plasma membrane protein (P less than 0.05) and an equilibrium dissociation constant of 12.1 +/- 2.8 nM. Competition studies on plasma membranes prepared from hepatocellular cancer tissue indicated no significant difference in the affinity of various prostaglandins to the receptor proteins as compared to normal hepatic tissue. It is assumed that the decreased 3H-PGE1-binding capacity found in human hepatocellular cancer tissue may reflect an alteration of the receptor protein content of the hepatocytes during carcinogenesis.

Adult↗
PubMed1989

In vivo tracing of indium-111 oxine-labeled human peripheral blood mononuclear cells in patients with lymphatic malignancies.

The in vivo migration of [111In]oxine-labeled peripheral mononuclear cells (PMNC) was studied in 20 patients with various lymphatic malignancies and palpable enlarged lymph nodes. The maximal labeling dose of 10 microCi (0.37 MBq) [111In]oxine/10(8) PMNC was found not to adversely influence either cell viability or lymphocyte proliferation in vitro. For in vivo studies, 1.5 X 10(9) PMNC were gained by lymphapheresis and reinjected intravenously after radioactive labeling, 150 microCi (5.55 MBq). The labeling of enlarged palpable lymph nodes was achieved in three out of three patients with Hodgkin's disease and in five out of five with high-malignant lymphoma, whereas three out of seven patients with low malignant lymphoma and no patient with chronic lymphatic leukemia had positive lymph node imaging. We thus conclude that PMNC retain their ability to migrate after [111In]oxine labeling and that these cells traffic to involved lymph nodes of some, but not all hematologic malignancies.

Adult↗
PubMed1989

Eicosanoids in the local regulation of haemostasis.

Prostaglandin 12, a potent antiplatelet agent, is formed by arterial wall cells to a differing extent. Various mechanisms are involved regulating synthesis and degradation. The mechanisms by which PGI2 exerts its biological action are still under debate. The most prominent ones are the action on fibrinolysis, thromboresistance, smooth muscle cell proliferation, extracellular matrix formation, endothelial stability, lipid metabolism, cytoprotection, and white blood cells among others. In vivo investigations have proven some of these mechanisms in human. The decreased thrombogenicity, endothelial stabilization, and reduction in intravascular lipids can be visualized under gamma-camera after autologous labelling of platelets or LDL, respectively. The local interaction of eicosanoids with other compounds regulates hemostasis in a rather complex system.

Alprostadil↗
PubMed1989

[Loss of high-affinity prostacyclin binding sites in patients with Basedow's disease].

Prostacyclin (PGI2) mediates like TSH its cellular effects through the interaction with specific binding sites associated with the adenylate cyclase-cAMP-system. Binding of PGI2 and the generation of cAMP induced by PGI2 was evaluated in thyroid tissue obtained intraoperatively from euthyroid and hyperthyroid patients with diffuse normofollicular colloid struma. Transformation of the binding data according to Scatchard revealed heterogeneity of the PGI2 binding sites in the tissue of euthyroid patients: the high-affinity binding sites were calculated to be 0.68 +/- 0.18 pmol/mg protein (Ka = 16.2 +/- 9.1 nM) and the low-affinity binding sites to be 5.4 +/- 1.6 pmol/mg protein (Ka = 151 +/- 43.1 nM). In contrast, in the hyperthyroid patients the low-affinity binding sites were not demonstrable and the high-affinity sites were significantly (p less than 0.001) reduced (0.17 +/- 0.05 pmol/mg protein, Ka = 83.5 +/- 19.6 nM). The competition of the agonist for the PGI2 sites in hyperthyroid patients was significantly (p less than 0.005) diminished (IC-50-values: 0.98 +/- 3.1 vs 46.9 +/- 12.1 microM). PGI2 stimulated cAMP-production in a dose-dependent manner. However, the basal value was significantly lower also in the hyperthyroid patients (p less than 0.001). The evidence of reduced PGI2 sites as well as reduced PGI2-induced cAMP production in the thyroid gland of patients with Graves' disease may indicate an important role for PGI2 to play in the modulation of thyroid cell function.

Adult↗