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Biomedical subjects

G Zbinden

Publications and source records attributed to G Zbinden.

At least 91 records · Page 5Linked to original sources
PubMed1980

Inhibition of 5-hydroxytryptophan nephrotoxicity by alpha-difluoromethyl-dopa, an inhibitor or L-amino acid decarboxylase.

Oral and intraperitoneal treatment of rats with L-5-hydroxytryptophan (5-HTP) caused dose-dependent kidney damage characterized by increase in kidney weight, functional disturbances and focal tubular necrosis. Alpha-Difluoromethyl-DOPA (DFMD), a drug that inhibits the conversion of 5-HTP to L-5-hydroxytryptamine (5-HT) abolished the nephrotoxicity of 5-HTP.

5-Hydroxytryptophan↗
PubMed1980

Assessment of emetine cardiotoxicity in a subacute toxicity experiment in rats.

We explored the usefulness of cardiovascular function studies for the detection and characterization of emetine cardiotoxicity in a subacute toxicity experiment. Rats received 1 mg/kg, s.c., emetine five times weekly for up to 7 weeks. In unanesthetized animals, statistically significant changes of the electrocardiogram (EKG) appeared in the following sequence: prolongation of QRS interval (5th day), flattening of T wave (beginning of 4th week), and prolongation of PR interval (end of 4th week). Terminal cardiovascular studies were conducted under urethane anesthesia. EKG changes were comparable to those recorded in conscious rats, but no decrease in T wave voltage occurred. Blood pressure and heart rate remained unchanged. Cardiac output was decreased after 5 and 7 weeks of treatment, when heart weights were also significantly reduced. The response of cardiac output and mean arterial blood pressure to intravenously injected norepinephrine and epinephrine remained unchanged. Catecholamine-induced arrhythmias occurred less frequently in emetine-treated animals than in controls. No significant structural lesions of the heart muscle were detected by light microscopy. The cardiotoxic effects observed in rats were similar to those reported in humans receiving the usual therapeutic dose of approximately 1 mg/kg/day. We conclude that cardiovascular function studies can make an important contribution to the predictive value of animal toxicity experiments.

Anesthesia↗
PubMed1980

Cryo-ultramicrotomy as a tool for the assessment of doxorubicine cardiotoxicity in rats.

Cryo-ultramicrotomy was tested as a tool for the assessment of cardiac damage induced by doxorubicine in rats. Slightly fixed specimens were cut at -80 or -90 degrees C (knife temperature -60 or -70 degrees C), and the ultrastructural changes observed were compared with those found in conventional epoxy sections. It is concluded that the cryo method, although using more elaborate equipment and being more painstaking, might yield more sensitive parameters for cardiac damage than epoxy sections.

Animals↗
PubMed1980

Electrocardiographic changes in rats during chronic treatment with antidepressant and neuroleptic drugs.

Five antidepressants, 3 phenothiazines and 5 butyrophenone neuroleptics were administered to rats orally at maximally tolerated doses for 22 weeks. The electrocardiogram (ECG) was recorded weekly. In animals treated with antidepressants quinidine-like changes of the atrioventricular and intraventricular conduction developed. There were also elevation of T-wave and right rotation of the electrical axis. Dibenzepine had the least effect on the ECG. In the group of phenothiazines chlorpromazine induced tachycardia and thioridazine widening of the QRS complex. Prothipendyl had no effect. ECG-changes induced by some of the butyrophenone derivatives were tachycardia and widening of the QRS-complex. In rats treated with protriptyline the ECG changes were correlated with drug concentrations in serum and myocardial tissue. The studies provided a quantitative assessment of the cardiac effects of clinically proven psychotropic drugs. They will be useful as a baseline for the preclinical evaluation of new derivatives.

Animals↗
PubMed1980

Biological assessment of chemical DNA damage in germ cells of male rabbits.

DNA damage represents a key step in mutagenesis and carcinogenesis. Excision repair has been described to be the major pathway restoring damaged DNA. Assaying DNA repair may thus illuminate the mechanism of mutagenesis and carcinogenesis and serve as an indicator of the mutagenic and carcinogenic potential of environmental chemicals and drugs. The paper demonstrates a practical application of these concepts. DNA damage induced by chemical substances in male germ cells of rabbits was assessed by the demonstration of DNA repair synthesis in meiotic and post-meiotic maturation stages. Incorporation of tritium-labeled thymidine was monitored in spermatozoa obtained by serial ejaculation. The test was validated with several standard mutagens and carcinogens, and its usefulness was demonstrated with a study on 3 suspected genotoxic drugs, i.e. hycanthone, isoniazid, and metronidazole.

Animals↗
PubMed1979

Unscheduled DNA synthesis in male rabbit germ cells induced by methylmethane sulfonate, cyclophosphamide and adriamycin.

Male rabbit germ cells were labelled by intratesticular injection of [3H]-thymidine (3H-T). In sperms of control animals, radioactivity was first demonstrated between the 40th and 43rd day after labelling, corresponding to preleptotene spermatocytes. In rabbits treated with 22.5 mg/kg methylmethane sulfonate (MMS), significant radioactivity was shown in sperms collected from day 19 ownwards. These cells derived from spermatocyes and early spermatids at the time of labelling. 3H-T incorporation into these cell populations represents unscheduled DNA synthesis (UDS), a repair process initiated after chemical damage of germ cell DNA. After i.v. injection of 20 mg/kg cyclophosphamide, an alkylating agent that must be activated, labelled sperms were found 28--37 days after treatment. This shows that UDS took place in spermatocytes during the pachytene and zygotene stages. Adriamycin (1.0 and 3.0 mg/kg) induced UDS during pachytene and zygotene stages of spermatogenesis. Sperm counts decreased during spermatogonial stages by a factor of about ten in cyclophosphamide and adriamycin treated rabbits. It was not changed after MMS-treatment.

Animals↗
PubMed1979

Application of fine-needle aspiration biopsy for the diagnosis of dysplastic and neoplastic liver cell changes induced by N-nitrosomorpholine in rats.

Male rats were treated with the hepatocarcinogen, N-nitrosomorpholine (NNM, 10 mg ad 100 ml drinking water) for 19 weeks. Repeated fine-needle aspiration biopsies of the liver were performed percutaneously. Cytomorphologic and cytochemical criteria were used for the characterization of dysplastic and carcinoma cells. The alterations seen in the smears were correlated with histopathologic findings in the punctured liver lobes. Cells showing type I dysplasia were recognized in smears obtained from day 7 on. They corresponded to the swollen, glycogen-free cells developing in zone 3 of the Rappaport acinus during the early treatment phases. In later stages type I dysplastic cells were observed in smears. This coincided with the development of neoplastic nodules seen in histopathologic preparations. Carcinoma cells were recognized first after 15 weeks. Marked gamma-glutamyl transpeptidase (gamma-GT) activity could be demonstrated cytochemically in biopsy smears and biochemically in biopsy homogenates during the early phases of NNM-treatment. Simultaneously, a rise in gamma-GT activity was also observed in the serum.

Animals↗
PubMed1979

The no-effect level, an old bone of contention in toxicology.

This discussion of the NEL presents some thoughts how toxicologists could be encouraged to use more sophisticated modern techniques for the study of various environmental chemicals. It is proposed to use the concept of the NEL only for data obtained by conventional techniques in routine toxicity experiments. Information on the mechanisms of the biologic effects of chemicals should, whenever possible, be used preferentially for the assessment of human risk and should therefore also be considered for the establishment of the ADI.

Dose-Response Relationship, Drug↗
PubMed1979

Differential DNA damage induced by chemical mutagens in cells growing in a modified Selye's granuloma pouch.

Rapid growth of granulation tissue was induced in rats by injection of croton oil into a subcutaneous air pocket. Growth characteristics of the granulation tissue were evaluated by histopathologic techniques and measurement of 3H-thymidine incorporation into DNA. The DNA of cells growing in the granuloma was labeled with 3H-thymidine. Subsequently, 4 classes of test chemicals (monofunctional and polyfunctional alkylating agents, DNA intercalating agents and chemicals not known to interact with DNA) were injected intraperitoneally. The presence of single-strand breaks was assayed in DNA of granuloma tissue using the alkaline elution technique. DNA breaks were primarily induced by monofunctional alkylating agents and were characteristic for each compound. DNA from animals treated with polyfunctional alkylating agents and DNA-intercalating agents showed a variable degree of resistance to methylmethane sulfonate-induced DNA breakage.

Alkylating Agents↗
PubMed1979

Quantitative analysis of rat behavior patterns in a residential maze.

A method for monitoring spontaneous locomotor patterns of rats during one day is described. The animals' locomotion is registered in a residential maze by 18 optical gates connected to a computer. Status changes of each optical gate are stored on a disk file and can be retrieved for complete session reconstruction and data analysis. The general features of a rat's behavior in the maze are discussed. Quantitative analyses and statistical comparisons between two sessions spaced two weeks apart and between a group of 4 control animals and 4 rats treated in utero with methylmercury chloride are performed. Following parameters are analysed as functions of time and maze location: locomotor and local activity, occupational duration and time per visit in the maze compartments. Angular dependences of path decisions and regional preferences of crossing at the alley bifurcations are observed. No changes of the measured parameters can be observed between the first and second sessions. Methylmercury treatment results in a consistently lower local activity during the night period and in differences of path preferences.

Animals↗
PubMed1978

DNA repair processes in germ cells demonstrated in ejaculated sperms of rabbits treated with methyl methane sulfonate.

Male rabbits were treated with a single i.v. injection of 22.5 mg/kg methyl methane sulfonate (MMS). 0--24 h later [3H]-thymidine was injected in both testicles. Incorporation of the isotope in germ cell DNA was demonstrated in ejaculated sperms. In controls labeled sperms were demonstrated first on day 40--43. These cells were in the preleptotene spermatocyte phase at the time of [3H]-thmidine injection. In rabbits treated with MMS significant radioactivity occurred in sperms collected from day 19 onwards. These cells were in late spermatocyte and early spermatid phase of maturation when [3H]-thymidine was injected. Incorporation of thymidine in these cell populations is interpreted as an expression of unscheduled DNA synthesis, a repair process initiated after chemical damage of germ cell DNA by MMS. The usefulness of the rabbit test system within the framework of conventional mutagenicity screening tests is discussed.

Animals↗
PubMed1978

Granuloma pouch assay. I. Induction of ouabain resistance by MNNG in vivo.

Growth of granulation tissue was induced in rats inside a subcutaneous air pouch by injection of croton oil. Granulation tissue, isolated and cultured in vitro, gave satisfactory and reproducible cloning efficiency of fibroblast-like cells. This experimental model system was used to study the induction of autosomal point mutations in vivo leading to ouabain resistance. For this purpose the mutagen MNNG was administered in the granuloma pouch, and the formation of ouabain-resistant clones was determined in vitro. Various application schedules, expression times in vivo and selective conditions in vitro were evaluated. The highest frequencies of ouabain-resistant clones were found when MNNG was injected into the pouch 24--48 h after induction of granulation tissue, followed by an expression time in vivo of 24--48 h. No ouabain-resistant clones were formed by cells isolated from untreated rats or from animals receiving the highest tolerated doses of MNNG per os or by intraperitoneal injection. The potential usefulness of the granuloma pouch assay for the evaluation of mutagenic and carcinogenic substances in vivo is discussed.

Animals↗