[Fiber analytical studies of the cochlear nerve in various mammals].
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Animals↗
Biomedical subjects
H Sinzinger
Publications and source records attributed to H Sinzinger.
[The spiral ganglion of the rat].
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Animals↗
Beneficial effect of PGI2 on circulating endothelial cells.
Endothelial damage is an early event in atherogenesis. Recent data present evidence that the counting of circulating endothelial cells in human peripheral blood may provide reliable information about endothelial integrity. We therefore assessed the influence of PGI2 on the number of circulating endothelial cells in patients suffering from peripheral vascular disease. As cigarette smokers and patients with hyperlipoproteinemia show an increased number of circulating endothelial cells, they were excluded from this investigation. PGI2 causes a certain drop in circulating endothelial cells. In parallel, a prolongation in platelet half-life can be noted. This is most pronounced at a daily duration of infusion between 4 an 12 h. A shorter duration of PGI2 therapy is less effective in reducing circulating endothelial cells. All of the three different doses used, however, were equally effective. Placebo controls were ineffective. These findings indicate that PGI2 might exert a rather long-lasting beneficial action on endothelial integrity and the hemostatic balance.
Adult↗
Platelet aggregation and reversible platelet aggregates in type I-diabetes staged by retinal fluorescein angiography.
In 70 patients with juvenile-onset, insulin-dependent (type I) diabetes and 75 age- and sex-matched controls the reversible platelet aggregates expressed as platelet count ratio (PCR) and the ADP-induced platelet aggregation were studied. Retinal microangiopathy was staged by retinal fluorescein angiography. The mean PCR of the patients (0.82 +/- 0.02) was statistically significantly lower than that of the controls (0.97 +/- 0.01). However, in different stages of retinopathy no significantly different PCR could be observed. ADP-induced platelet aggregation (0.5 and 1.0 micromol/l) exhibited a higher reactivity of diabetic platelets, but with the exception of tangent alpha (see later), the differences were not statistically significant in comparison to the controls. After collagen-induced platelet aggregation (0.5 and 1 microgram/ml) the lag time in diabetics was significantly (p less than 0.001) lower than in the controls, whereas the other quantitative parameters exhibited higher platelet reactivity in general, though not statistically significant. No relationship between PCR and the in vitro induced aggregation was found. The degree of retinopathy had no significant influence on platelet aggregation. In general, the data demonstrate an increase in sensitivity of platelets in juvenile-onset diabetics, whereas no influence of stage of microangiopathy could be detected.
Adenosine Diphosphate↗
Morphological changes in the umbilical arteries of babies born to pre-eclamptic mothers: an ultrastructural study.
The umbilical arteries of babies from ten normal pregnancies and from ten babies born to pre-eclamptic mothers were studied. Ultrastructurally, there were marked abnormalities of umbilical arterial morphology in the pre-eclamptic group. A loss of intercellular junctions, distension of the endoplasmic reticulum and an increase in cell organelles in the endothelial cells leading to a partial de-endothelialization was noted. Smooth muscle cells showed the morphological features of metabolic activation. These ultrastructural findings can be attributed to fetal hypoxia and to disturbances in cellular lipid metabolism; they suggest that there may be an abnormal fetal arterial blood flow in maternal pre-eclampsia.
Adult↗
(Iso) Prostaglandins in saliva indicate oxidation injury after radioiodine therapy.
UNLABELLED: As salivary glands concentrate radioiodine the radiation injury associated with 131I-therapy may result in sialoadenitis and xerostoma leading to a lasting impaired quality of life. Recently we reported about prostaglandin concentration changes as biochemical markers for radiation injury. Isoprostanes, a new family of prostaglandin-like compounds, have been demonstrated to be reliable markers for oxidation injury in vivo. PATIENTS AND METHODS: In this study we examined the levels of 8-epi-PGF2alpha, the major member of the isoprostane family in 24 patients undergoing 1311 treatment in different doses for hyperthyroidism and differentiated thyroid cancer. 6 healthy sex and age-matched volunteers were monitored in parallel. Saliva(iso)prostaglandins were determined before 131I treatment, as well as 1, 3, 7, 14, 21, and 28 days, and 2, 3, and 6 months after therapy. RESULTS: 8-epi-PGF2alpha showed a significant 1311 dose-dependent temporary increase. The alterations were comparable in all investigated patients and significantly higher in cigarette smokers. TXB2 and 6-oxo-PGF, showed a dose-dependent increase too. TXB2 was higher in cigarette smokers and 6-oxo-PGF1alpha lower as compared to non-smokers. CONCLUSION: These results clearly demonstrate a dose- and time-dependent tissue (TXB2, 6-oxo-PGF1alpha) and oxidation in-jury (8-epi-PGF2alpha) after 131I-therapy in the salivary glands.
Adult↗
The isoprostane 8-epi-PGF(2alpha) is a valuable indicator of oxidative injury in human heart valves.
To date, little information is available concerning oxidative injury in human cardiac valves. Therefore, we sought to investigate whether the isoprostane, 8-epi-PGF(2alpha), a novel oxidative stress marker, is localized in aortic and pulmonary valves derived from explanted hearts of patients suffering from idiopathic dilative cardiomyopathy (IDC). By using semiquantitative immunohistochemistry, we demonstrated that 8-epi-PGF(2alpha) is localized in both valves with pulmonary valves accumulating more of this isoprostane compared to aortic valves (36.69+/-12.04% vs. 31.54+/-11.49%, P<.05). These results were confirmed by a radioimmunoassay (RIA) analysis showing a similar, but not significant, difference between the two valves (288.50+/-72.18 pg/mg protein in the pulmonary valves and 267.30+/-58.77 pg/mg protein in aortic valves, P=.09). Considering the data presented in this study, we suggest that 8-epi-PGF(2alpha) is a valuable indicator of oxidative injury in human semilunar valves.
Adult↗
Effect of black tea on (iso-)prostaglandins and platelet aggregation in healthy volunteers.
Flavonoids among others are found in tea. Many of them were shown to exhibit antioxidative action in vitro. We examined the effect of a 1-month consumption of 500 ml black tea containing 2.0 mg quercetin. While single tea consumption 2 h after finishing the intake did not affect any of the parameters (8-epi-PGF(2 alpha) in plasma and serum, 11-DH-TXB(2) and ADP-induced platelet aggregation) examined at all, 1-week consumption and even more than 1 month regular tea intake significantly decreased most of the parameters. The effect was somewhat more pronounced for females as compared with males, the values for 11-dehydro-thromboxane B(2) (11-DH-TXB(2)) and ADP-induced aggregation reached the level of significance in females only. These data show that regular daily black tea consumption for 1 month improves platelet function and decreases thromboxane and 8-epi-PGF(2 alpha) to a varying extent indicating a reduced in vivo oxidation injury.
Adenosine Diphosphate↗
Binding of [99mTc]chondroitin sulfate to scavenger receptors on human chondrocytes as compared to binding of oxidized [125I]LDL on human macrophages.
Chondroitin sulfate (CS) used for treatment of osteoarthritis exerts distinct effects on human articular chondrocytes in vitro. We performed a binding analysis with 99mTc-labeled CS (Condrosulf, a commercial CS preparation containing calcium stearate) and cultured human chondrocytes in order to evaluate the presence of specific receptors. Saturation binding at 37 degrees C for 2 h revealed the presence of high-affinity binding sites for CS with a Kd of 2.3 x 10(-9) mol/L and a Bmax of 5.0 x 10(8). Extensive dialysis of Chondrosulf led to a decrease of the binding affinity by 52.5 +/- 19.5% and of the number of CS binding sites/cell by 62.0 +/- 14.0%, demonstrating that the additive present in the Condrosulf preparation enhances CS binding. The nature of the binding site is not yet known but evidence exists in the literature that the scavenger receptor CD36, thoroughly investigated on macrophages, is also found on chondrocytes and might be involved in CS binding. Therefore, we undertook a comparative binding study with human monocytes and labelled LDL and oxidized LDL, the latter being a postulated atherogenic agent in atherosclerosis. For [125I]-LDL binding we found a Kd of 0.45 x 10(-8) mol/L and a Bmax of 0.14 x 10(6) on quiescent monocytes and for [125I]-(ox)LDL binding a Kd of 1.8 x 10(-8) mol/L and a Bmax of 1.3 x 10(6) using LPS-activated monocytes. These data are comparable to the binding affinity found for lipoprotein-proteoglycan-complexes and hence are an indication but not a proof that CD36 is involved in CS binding to human chondrocytes.
Adult↗
Homocysteine--a pathophysiological cornerstone in obstetrical and gynaecological disorders?
Homocysteine, a product of the methionine cycle, is known to play an important role in cardiovascular diseases, neurological disorders and embryology, and in very important, fast growing fields concerning obstetrics and gynaecology. Therefore, we attempted an actual overview on possible obstetrical and gynaecological disorders as a consequence of an impaired methionine cycle. We tried to evaluate all mechanisms concerning homocysteine metabolism in order to look for hypothetical possibilities of therapeutic interventions. Using MEDLINE starting in January 1966, a search was conducted for articles published in which homocysteine was included as a subject heading or a text word. This search was also specified in combination with other key words such as obstetrics, pregnancy, gynaecology and cancer. Additional sources were identified through cross-referencing. All sources found were examined with regard to providing substantial information on our topic. The information obtained was divided into articles dealing with homocysteine and the methionine cycle itself, homocysteine and pregnancy, and homocysteine and hormones, including menopause, hormone replacement therapy and oral contraceptives. Another group was concerned with other special gynaecological aspects of the methionine cycle. We suggest that elevated concentrations of homocysteine could be a marker and perhaps a cause of, or contributive to, a wide range of obstetrical and gynaecological disorders.
Animals↗
Transient drug-induced myocardial dysfunction is not ameliorated by PGI2 in dogs.
Prostacyclin (PGI2), a potent vasodilatory substance that effectively inhibits platelet aggregation is under clinical investigation for the treatment of angina pectoris. We studied the effects of PGI2 on transient drug-induced myocardial dysfunction in anesthetized, thoracotomized dogs. Regional myocardial function was assessed using two pairs of piezoelectric transducers and a multidimensional measuring gauge; one pair was implanted in the distribution area of the left circumflex branch (LCX) and the other in the distribution area of the descending branch (LAD) of the left coronary artery. After intravenous injection of isoproterenol (ISO), which led to an increase in systolic shortening in the LCX and LAD areas, a critical stenosis was performed on the LCX and maintained at this level. Intravenous ISO injection now induced regional dysfunction in the LCX-dependent segment with the occurrence of systolic bulging. Infusion of PGI2 at a dosage of 100 ng/kg/min caused a decrease in arterial blood pressure and an increase in heart rate, but had no effect on regional myocardial function. ISO-induced myocardial dysfunction in the critically stenosed LCX segment, which was observed before PGI2 administration, was not ameliorated, but rather aggravated, by PGI2. It may be concluded that PGI2 does not improve normal or ISO-stimulated myocardial function in pressure-dependent perfused areas of the heart.
Animals↗
8-Epi-PGF2alpha and 6-oxo-PGF1alpha in human (varicose) veins: influence of age, sex, and risk factors.
The isoprostane 8-epi PGF2alpha is a vasoconstrictive, mitogenic, proliferative, and mild proaggregatory agent. We examined 8-epi-PGF2alpha and 6-oxo-PGF1alpha from venous tissue derived from varicose (venous) surgery by means of a specific radioimmunoassay. A total of 336 samples from 82 patients (50 females, 32 males; aged 22-68 years) were examined. Tissue samples were classified according to normal, dilated, and varicose. Of these, 94 samples from 31 patients (20 females, 11 males; aged 29-64 years) with additional risk factors (cigarette smoking, hyperlipidemia, diabetes mellitus) were determined in the same way. Mean absolute values for 6-oxo-PGF1alpha are not significantly higher for dilated segments followed by varicose and intact samples. No significant age and sex differences can be monitored. Presence of risk factors, however, results in a significantly diminished 6-oxo-PGF1alpha, irrespective of morphology. 8-Epi-PGF2alpha again showed no age and sex dependence, its presence in varicose segments, however, was significantly (p<0.01) decreased. Risk factors resulted in a significantly increased 8-epi-PGF2alpha. These data indicate that the influence of risk factors on vasomodulatory (iso-)eicosanoids of human veins is more pronounced than the actual morphologic stage. Lower 8-epi-PGF2alpha in varicose veins may shift the venous tone toward vasodilatation and contribute to development and progression of varicosis.
6-Ketoprostaglandin F1 alpha↗
Platelet deposition on human atherosclerotic lesions is decreased by low-dose aspirin in combination with dipyridamole.
Eighteen patients with ischaemic peripheral vascular disease were treated for a 5-week period with either 20 mg aspirin daily, 75 mg dipyridamole three times daily or a combination of these two treatments. Before and after 4 weeks' treatment autologous platelet labelling with 111In was carried out and sites of active vascular platelet uptake monitored, and platelet half-life measured. Neither aspirin nor dipyridamole alone had any effect on platelet uptake or on platelet half-life. The combination of aspirin and dipyridamole resulted in a significant decrease in platelet uptake and a nonsignificant trend towards prolongation of platelet half-life. These findings suggest that this combined therapy may be of benefit in the treatment of atherosclerosis in man.
Aged↗
Binding of long-term glycated low density lipoprotein and AGE-albumin by peripheral monocytes and endothelial cells.
Modification of low density lipoprotein (LDL) and plasma or tissue proteins by non-enzymatic glycation culminating in the formation of advanced glycation endproducts (AGEs) is one of the essential pathomechanisms leading to diabetes-associated long-term complications. We compared binding of glycated, glycoxidated and oxidated LDL by peripheral monocytes in activated and quiescent form. Interaction via specific receptors was different for glycated as compared to (glyc)oxidated LDL-modifications. In addition, binding of glycated LDL to quiescent and activated human umbilical vein endothelial cells was studied. In patients with insulin-dependent diabetes mellitus (IDDM), AGE-binding was significantly increased as compared to healthy individuals. Specific and non-specific monocyte binding mechanisms were detected, and both were significantly increased in IDDM patients. Specific and non-specific binding strategies possibly act in concert to eliminate circulating AGEs, which are instrumental in the development and progress of microangiopathic and macroangiopathic complications of diabetes mellitus.
Binding Sites↗
[Experimental ligature of the liver lobe artery in the rat].
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Animals↗
[Prostaglandin synthesis in oral squamous cell carcinoma].
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Carcinoma, Squamous Cell↗
[Streptomycin-induced damage of the spiral ganglion].
The neuronal density in the spiral ganglion was investigated in normal and in streptomycin-intoxicated guinea pigs. Streptomycin was administered in a dose of 250 mg/kg for 21 days. 6 weeks after the streptomycin exposure a histological examination revealed a decrease in ganglion cell density in the spiral ganglion, with maximum loss in the apical portion of the ganglion. As mechanisms of the ototoxic effect, a secondary degeneration of spiral ganglion cells after hair cell loss or a primary neurotoxic degeneration are discussed.
Animals↗
Technetium-99m-tetrofosmin: a new agent for melanoma imaging?
The aim of our study was to examine whether technetium-99m 1,2-bis[bis(2-ethoxyethyl) phosphino]ethane (tetrofosmin) a lipophilic, cationic tracer which was first developed for myocardial perfusion imaging, could be a new radiopharmaceutical for melanoma imaging. We therefore used two human cell lines, SK-MEL 28 and 5i8 A2 (n = 6, cell concentration 106/ml, incubation at 22 degrees C and 37 degrees C, 50-100 approximately lCi/ml Tc-99m-tetrofosmin, time of incubation 10-180 minutes). The cellular uptake by both cell lines was determined. In contrast to another non- melanoma tumor cell line MCF-7 (a human adenocarcinoma breast cancer) which reached steadystate almost immediately (within 10 minutes), the cellular uptake of SK-MEL-28 increased after 60 minutes and showed a very high uptake (> 10%) after 120 minutes and decreased after 180 minutes (6-8%), while the uptake in 518 A2 cells was about 5% after 90 minutes. Our data show that Tc-99m-tetrofosmin could be a promising agent for melanoma imaging.
Biological Transport↗