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Biomedical subjects

G Trieb

Publications and source records attributed to G Trieb.

At least 19 recordsLinked to original sources
PubMed2003

The Himalayan rabbit (Oryctolagus cuniculus L.): spontaneous incidences of endpoints from prenatal developmental toxicity studies.

The historical database represents the spontaneous, i.e. normal changes of characters, in laboratory animals, and is a must for the assessment of toxic effects of compounds. For the Himalayan rabbit (CHBB:HM, SPF) background data were collected from the control groups of regulatory studies between 1968-1999 in the Biberach laboratory of Boehringer Ingelheim (Germany). In the present study these data were compared with the background data from the years 1974-1984, with those from the Ingelheim laboratory, Germany (1977-1984) and those from the breeding colony at Kawanishi, Japan (1971-1991, 1972-1984). Fertility in the Biberach laboratory was relatively constant through the years, due to the strict breeding system. Litter parameters (corpora lutea, implantations and viable fetuses), including fetal sex distribution and fetal weight, were constant in the Biberach laboratory through the years and compared well with the data from Ingelheim and Kawanishi. From these three laboratories the results of spontaneous changes in fetal morphology above 0.1% incidence suggest a pattern of deviations from the Bauplan (fundamental body plan). These comprise synosteosis of sternebrae, lumbar (additional) ribs, hypoplasia of 12th rib, status of ossification, aplasia of gall bladder, hypoplasia of gall bladder, incompletely subdivided lung, dilated ventricle of heart, deviations at the A. carotis and at the aortic arch and flexure of paw. The absence of a time-dependent statistical trend indicates that the spontaneous change of endpoints remained constant through the time axis. Comparison with the spontaneously changed fetal morphology of the other strains (NZW, JW, SF rabbits) does not provide support for their being a totally strain-specific pattern, and this pattern may be closer to the species than specific to a single strain. The firm patterns of deviations in fetal morphology provide suitable and valuable markers for assessing toxic effects on ontogenesis. According to our experience these morphological endpoints react very sensitively to teratogenic compounds, which is demonstrated by increased incidences. Our knowledge of evolution of organisms and of mechanisms leading to morphological deviations points to a strict selection of phenotypes. For laboratory animals the decisive selection factors are defined by man. These are nutritive factors, environmental conditions, the mating system, handling and treatment, and experimental design. All these factors have to be held constant through the years, which is an absolute pre-condition for the application of valid historical data. The Himalayan rabbit is highly suitable for use in developmental toxicity studies due to the stability of reproductive data within the same laboratory over a period of more than 30 years, due to the similarity of reproductive data among three different laboratories, and due to an absence of relevant differences to the reproductive data of other rabbit strains.

Abnormalities, Drug-Induced↗
PubMed1997

Comparative cardiac toxicity of the i.v. administered benzimidazole pyridazinon derivative Pimobendan and its enantiomers in female Beagle dogs.

The new positive-inotropic and vasodilatating drug Pimobendan (racemate), 4,5-dihydro-6-[2-(4-methoxyphenyl)-1H-benzimidazole-5-yl]-5-methyl-3 (2-H)-pyridazinone, and its enantiomers were investigated with regard to their cardiotoxicity in young adult female Chbb: Beagle dogs. The racemate and the (-)-isomer (eutomer) were intravenously injected once daily for 4 consecutive weeks at doses of 0.25, 0.75 and 2.25 mg/kg, and the (+)-isomer (distomer) at doses of 0.75, 2.25 and 6.75 mg/kg, respectively. Clinical signs, hematological, clinico-chemical, ophthalmologic and electrophysiological parameters were monitored. Plasma concentration-time profiles of the parent compound and the major metabolite UD-CG 212 were established on day 1 and in week 4 using an HPLC assay. Partial areas under the curves from 0.08 h to 1 h (AUC0.08-1 h) as well as the plasma concentration at time point 0.5 h/C0.5 h) were used for statistical calculations. Necropsy and histopathologic examination were performed after completion of the treatment period. Reduction of the blood pressure occurred already at low dosages of the racemate and the eutomer, but only in high dose distomer-treated animals. A tendency to tachycardia developed only in high dose females receiving the racemate. Consequently, with respect to the pharmacological effects and the adverse events, the racemate is equivalent to the eutomer. Plasma concentrations of parent compound and metabolite were dose-linear for racemate, eutomer and distomer within the dose range 0.25-2.25 mg/kg.d at both time points. There were no significant effects of form or repeated administration. A moderate increase of AUC0.08 1 h and C0.5 h could be seen on day 23 for the distomer indicating a stereoselektive metabolism of the latter. Histologic changes of the valvular and parietal endocardium being termed jet lesion were observed after administration of the racemate (> or = 0.75 mg/kg.d) and the eutomer (> or = 0.25 mg/kg.d) at distinctly lower doses than after the distomer (> or = 2.25 mg/kg.d). Furthermore, extent and severity of the morphologic lesions were found to be higher in dogs exposed to the racemate or the eutomer than in those receiving the distomer. The results gave evidence that the so-called cardiotoxicity by Pimobendan in dogs resulted from the exaggerated pharmacodynamic effect but not from the chemical nature of the compound per se. They corroborate also the previously raised assumption that the exaggerated pharmacodynamic activity of cardiotonic compounds in the broadest sense accounts for their morphologic adverse effects in experimental animals.

Animals↗
PubMed1985

The influence of castration on cell proliferation in the adrenal cortex of female rats.

Proliferation kinetics in the zones of the adrenal cortex of female rats after castration are reported. Following ovariectomy a wave of increased cell proliferation was observed in the zona glomerulosa and zona fasciculata after 1 and 2 days respectively. Increased cell proliferation in the zona reticularis was only slight. Cell proliferation returned to the level in control animals at 4 weeks. It is assumed that the regulative process following ovariectomy takes place directly in the adrenal cortex but it is possible that steroid metabolism in the liver is of importance. No relationship between the 3H-TdR labelling index (LI) and the mitotic index (MI) was observed.

Adrenal Cortex↗
PubMed1984

Comparative studies on the circadian rhythm of corticosterone, lipid and cholesterol levels in adrenals and blood of rats.

The time-dependent relationship of corticosterone, lipids and cholesterol over a 48-hr period was studied in the adrenals and blood of rats. In addition an attempt was made to determine whether there was a reciprocal dependence among these compounds and also a correlation between corticosterone and cholesterol in the adrenals and blood. Corticosterone and cholesterol exhibit a circadian rhythm in the adrenals and blood. The same is true for lipids in the serum. A reciprocal dependence between the compounds in the adrenals and blood could not be demonstrated. Only the time-dependent processes of the corticosterone content in the adrenals and plasma are well correlated with each other. High levels of these steroids in the adrenals are associated with high levels of these steroids in the plasma and vice versa. An inverse correlation between corticosterone and cholesterol exists in the adrenals and in blood. Maximal levels of corticosterone correspond to minimal levels of cholesterol and vice versa.

Adrenal Glands↗
PubMed1984

Diagnostic problems in upper gastrointestinal bleeding.

In this editorial problems of different diagnostic procedures, the time of endoscopy, i.e. emergency endoscopy procedures, and its complications, are discussed. Criteria for a risk patient and possibilities of endoscopic therapy or operation are discussed.

Endoscopy↗
PubMed1983

[Hemodynamic effects of isosorbide-5-mononitrate in coronary heart disease. A comparison of acute and chronic treatment].

The haemodynamic effect of isosorbide-5-mononitrate (ISMN) was studied in 20 patients with coronary heart disease. Three hours after the first and single dose of 50 mg ISMN, both at rest and on exercise there was a significant decrease in pulmonary artery mean pressure of 30%, while heart rate and systemic blood was an anti-anginal effect, as objectified by the angina threshold and return to normal of previously depressed S-T segments during exercise. After administration of 50 mg ISMN, three times daily for seven days, a single dose of 50 mg ISMN on the eighth day produced a fall in pulmonary artery mean pressure three hours after administration, of only 25% at rest and 20% on exercise, while the anti-anginal effect remained unchanged. Six hours after administration there were no significant changes in haemodynamic variables compared with the initial values. The reduced fall in pulmonary artery mean pressure during chronic administration is interpreted as the development of tolerance with decreased venous pooling, while the unchanged anti-anginal effect is explained by the site of action of the nitrate on the coronary arteries and on the collateral circulation with positive blood redistribution.

Adult↗
PubMed1983

Hemodynamic effects of isosorbide-5-mononitrate in acute and chronic treatment of coronary heart disease.

Hemodynamic effects of isosorbide-5-mononitrate (IS-5-MN) were studied in 20 patients with coronary heart disease. Three hours after the first administration of 50 mg IS-5-MN we found a significant decrease in mean pulmonary artery pressure, while heart rate and arterial blood pressure remained unchanged. Concomitant with the hemodynamic effects we found a decrease in angina pectoris and normalization of exercise-induced ST depression. After 50 mg IS-5-MN three times daily for 1 week the repeated acute administration of a single dose of 50 mg produced a fall in mean pulmonary artery pressure at rest (-25%) and during exercise (-20%), while the antianginal effect was unchanged. Six hours after a repeated single dose we found no change in hemodynamic parameters as compared with the control levels before treatment. The decreased effect on the pulmonary artery pressure under chronic treatment is discussed as a development of tolerance with decrease of venous pooling. The unchanged antianginal effect is difficult to understand, and may be interpreted as due to an influence on the coronary vessels and collateral blood flow.

Aged↗
PubMed1982

Autoradiographic studies of the diurnal rhythm of the cell proliferation in the adrenal cortex of the rat.

With the aid of the autoradiographic technique we examined the question of diurnal or circadian rhythm of the cell proliferation as well as the mitotic rate in the three zones of the adrenal cortex of the rat. To evaluate the diurnal rhythm it is necessary to run experiments within 24-hour intervals. In order to examine observed variations as to their reproducibility we prolonged our investigations over a period of 72 hours. The proliferation activity as well as the mitotic rate in the zona glomerulosa show no diurnal rhythm. This is not so in the zona fasciculata. Here we find a correlated circadian rhythm for both parameters.

Adrenal Cortex↗
PubMed1982

The influence of beta-adrenoceptor antagonists with and without intrinsic sympathomimetic activity on local wall motion abnormalities in patients with coronary heart disease.

1 A single-blind randomized study of the effects of a beta-adrenoceptor antagonist with intrinsic sympathomimetic activity (pindolol 0.4 mg i.v., n = 10) and a drug lacking this property (metoprolol 5 mg i.v., n = 11) on local wall motion abnormalities was carried out in 21 patients with coronary heart disease and anterior wall hypokinesia. 2 The drugs produced similar changes in left ventricular end diastolic pressure (LVEDP) and end diastolic volume index (EDVI) but differed in their effects on heart rate and ejection fraction. Pindolol did not exert any marked effect on heart rate or ejection fraction whereas after metoprolol treatment both were significantly decreased. 3 Shortening of the hypokinetic wall segments was improved by both drugs. Shortening of the non-hypokinetic contralateral segments was unchanged after pindolol administration but was decreased after metoprolol. 4 The differing effects of beta-adrenoceptor antagonists on regional wall motion appear to be dependent on the presence or absence of intrinsic sympathomimetic activity.

Adrenergic beta-Antagonists↗
PubMed1982

[Influence of betablocking agents with and without intrinsic sympathicomimetic activity (ISA) on local wall-motion disorders in patients with coronary heart disease].

UNLABELLED: A single blind randomized study on the effect of betablockers with (Pindolol = P, 0.4 mg i.v., n = 10) and without (Metoprolol = M, 5 mg i.v., n = 11) intrinsic sympathicomimetic activity (ISA) on local wall-motion abnormalities was performed in 21 patients with coronary heart disease in anterior wall hypokinesia. Before and 10 minutes after intravenous application of P or M strokes, volume index, cardiac index, heart rate, systolic and enddiastolic left-ventricular pressure were measured. The left-ventricular volumes were calculated biplane with the area-length method of Dodge and Sandler. Analysis of wall-motion disorders were performed by hemichord method measuring 7 hemiaxis and 1 long axis. RESULTS: Similar hemodynamic effects of both beta-blockers were found on LVEDP und LV-EDVI. Different effects were observed on heart rate and ejection fraction. With M heart rate and ejection fraction decreased, with P heart rate and ejection fraction increased significantly due to the intrinsic sympathicomimetic activity (ISA). Shortening of hypokinetic wall segments was improved by both P and M, shortening of non-hypokinetic contralateral segments, however, remained unchanged with P and decreased with M. With P shortening of chords was improved, whereas with M shortening of chords decreased. Our findings suggest that in therapy of patients with coronary heart disease differential use of beta-blocking agents with or without ISA has to be discussed.

Adrenergic beta-Antagonists↗
PubMed1982

[Runaway pacemaker caused by the defect of a Lem-Dynacor pacemaker (author's transl)].

Caused by the defect of a Lem-Dynacor pacemaker, a critical diminution of the period time till 20 ms developed. Fortunately, ventricular fibrillation did not occur because of diminution of the impulse amplitude beyond the threshold value of ventricular stimulation. Recognition of the defect with the ECG is possible if considered. It is easy to confuse with overlapping of alternating current.

Bradycardia↗