Biomedical subjects

W Rebel

Publications and source records attributed to W Rebel.

10 recordsLinked to original sources

PubMed1995

Diagnostic efficiency of troponin T measurements in rats with experimental myocardial cell damage.

A cardioselective parameter has been available for about 2 years since the development by KATUS of an immunoassay for cardiac Troponin T (TnT). The major advantages of this TnT assay are its cardiospecificity and its sensitivity. The parameters usually determined in toxicity studies in rats to detect alterations in the myocardial cells, e.g. aspartate aminotransferase (ASAT), creatinine kinase (CK) and lactate dehydrogenase (LDH), are either of low sensitivity in this species or give falsely high results as the consequence of stress or haemolysis. We therefore investigated in the present study how well Troponin T, determined with the ELISA Troponin T from Boehringer Mannheim, can detect experimentally induced myocardial lesions in rats. In order to achieve hypoxic damage of the cardiomyocytes in these experiments in rats, male Sprague-Dawley rats were given two doses of 4 mg/kg isoprenaline each (Aludrin from Boehringer Ingelheim, FRG) subcutaneously. The second dose was given 7 h after the start of the experiment. Serum samples were analysed for Troponin T (TnT) levels and, for comparison, aspartate aminotransferase (ASAT), creatine kinase (CK), and lactate dehydrogenase (LDH). Histological examinations of the heart muscle were performed 24 and 96 h after the first injection. As expected, histological examinations of the isoprenaline-treated animals revealed marked myofibrillic degeneration of the myocardium 24 h after the first injection. Markedly elevated serum TnT levels (up to 7.9 ng/ml) were already evident in these animals after 6 h. TnT values decreased with time, but were still statistically significant after 48 h. Of the well-established indicators for diagnosing myocardial infarction, only ASAT showed transient statistically significant increases over 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

[Elevation of 7-dehydrocholesterol concentrations in serum and liver and pericentral peroxisome proliferation in hepatocytes of rats after inhibition of cholesterol biosynthesis by BM 15,766].

Sprague-Dawley rats of both sexes were treated for three months with BM 15,766, an inhibitor of cholesterol biosynthesis in conjunction with standard or high-fat and high-cholesterol diets. In serum and livers of all drug-treated rats lowered cholesterol concentration associated with an increase of 7-dehydrocholesterol (7-DHC) was found. Electron microscopy of the liver showed a distinct proliferation of peroxisomes and an increase of dumb-bell shaped mitochondria in the pericentral zone 3. Abnormal-shaped peroxisomes with DAB-negative loops attached to their membranes were found in the intermediate zone 2. These alterations were more accentuated in drug-treated rats fed standard diet, then in treated rats receiving a high-fat and high-cholesterol diet. The observations demonstrate, that the increase of 7-DHC is due to the inhibition of 7-DHC-delta 7-reductase by BM 15.766 and emphasize the zonal heterogeneity of hepatocytes. The relevance of these observations for the investigation of the human Smith-Lemli-Opitz syndrome, in which also decreased plasma-cholesterol levels and an increase of 7-DHC were reported, is discussed.

Animals↗

PubMed1992

Stimulation of bone marrow by administration of excessive doses of recombinant human erythropoietin.

Recombinant human erythropoietin (rhEPO) was administered intravenously to Beagle dogs in daily doses of 100, 500 and 3000 units/kg/day for 3 months. The high dose was more than 200-fold the therapeutic human maintenance dose. Such excessive rhEPO doses elicited extreme erythropoiesis. There was a dose-dependent stimulation of bone marrow fibroblasts, leading to bone marrow fibrosis in some of the high dose animals. The extent of myelofibrosis was intra- and interindividually different in various bones. Sternebrae proved to be practical for morphometric studies. The point-counting method was used for measurement. The portion of fatty tissue, sinusoids and fibrous tissue in the medullary space as well as the number of blood vessels and megakaryocytes were calculated. Such experimental conditions are not of relevance in human patients whose rhEPO therapy is interrupted as soon as their PCV reaches 35 vol%. Experimentally induced myelofibrosis should therefore not be considered as a risk in patients receiving therapeutic doses of rhEPO.

Adipose Tissue↗

PubMed1989

Automatic image analysis as a valuable aid for the objective assessment of the enlargement of hepatocytes in toxicological studies.

Evaluation of histopathological slides is a subjective science; objectivity is needed, especially with minimal alterations. Quantitation using measurement procedures is of special value in toxicological studies. The present study tests a method in which the hepatocytic nuclei were measured per area of liver tissue, excluding the sinusoidal space. Different grades of hepatocellular enlargement were induced by different dose levels of a test compound (combination of two diuretics). The method demonstrates the well-established dose dependence of liver cell enlargement and permits differentiation between slight drug-induced enlargement and the normal variation in cell size. Special reference is made to avoid measurement artefacts.

Animals↗

PubMed1975