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G Zbinden

Publications and source records attributed to G Zbinden.

At least 19 recordsLinked to original sources
PubMed1992

Decrease of epinephrine-induced arrhythmia threshold in ethanol exposed rats.

An association between cardiac arrhythmias and ethanol use has been observed for some time. The sympathetic nervous system presumably plays an important role in the manifestation of cardiovascular ethanol responses. Therefore, we investigated the effects of ethanol treatment on epinephrine-induced arrhythmias. Female Wistar rats received 10 vol% ethanol or 2.5% glucose (control group) in their drinking water for 45 days. In ether anesthetized animals of both groups epinephrine (10 micrograms/kg.min) was infused via a lateral tail vein. The threshold dose for arrhythmias after epinephrine infusion (mainly 2nd and 3rd degree AV-blocks) was reduced beginning 2 days after the start of the ethanol treatment and the incidence of AV-blocks during epinephrine infusion was increased. During the ethanol treatment the prohypertensive epinephrine effect was slightly increased. The reflex bradycardia was not changed after repeated epinephrine infusion by ethanol treatment, whereas it was nearly abolished in the control group. No blood ethanol could be detected during the time of epinephrine infusion (9-12 a.m.), but determinations at 11 p.m. yielded a concentration of 0.13 +/- 0.02 mg/g. The results show that the epinephrine-induced bradyarrhythmia threshold is reduced and the frequency of arrhythmic events is augmented in rats exposed to ethanol in the drinking fluid.

Animals↗
PubMed1992

Cardiotoxicity of vasodilators and positive inotropic/vasodilating drugs in dogs: an overview.

Standard toxicological studies in dogs using high doses of vasodilators and positive inotropic/vasodilating agents give rise to a species-specific cardiotoxicity. The reason may be the extreme sensitivity of the dog to the pharmacological effects of these drugs; exaggerated pharmacodynamic effects and prolonged disturbance of homeostasis mechanisms often are responsible for the observed organ lesions. An assessment of the toxicological relevance and the risk for patients taking the drugs at therapeutic doses cannot be made without taking into account their pathomechanisms and the pathophysiological basis of the exceptional reaction patterns occurring in dogs. A large series of vasodilating and positive inotropic agents are presented, their pharmacological properties are described, and toxicological effects in dogs are compared. In view of the poor correlation between the distinct cardiac lesions induced in dogs and a lack of comparable toxicity in humans, it appears desirable to reassess the adequacy of the standard toxicological approaches for these substances.

Amines↗
PubMed1991

Predictive value of animal studies in toxicology.

The three main purposes of experimental toxicology are (1) determination of the toxicological spectrum in selected laboratory animal species; (2) extrapolation to other species and prediction of adverse effects in man; and (3) determination of safe levels of exposure. Toxicology has reached a satisfactory level of performance in identifying toxicity in animals, and experimental techniques are now available to characterize the toxicological potential of chemical substances in great detail. In many instances, extrapolation of toxicological findings in animals to man is possible. It must also be admitted that toxicological studies have, at times, failed to predict human toxicity. In many cases, this can be explained by biological differences between animals and man. A particularly difficult problem is the "low incidence responses" that occur only in especially sensitive individuals. They represent a challenge that can be met only be a determined research effort. Failure to predict toxic responses in man is sometimes also brought about by the toxicologists' own faults. It is essential, therefore, that we analyze the errors committed in the past and continuously evaluate and improve our performance. Society's demand for specific safe levels of exposure is difficult to meet. After a long period of confusion and confrontation, toxicology appears to be on the road to a truly science-based methodology for risk assessment.

Animals↗
PubMed1990

Alternatives to animal experimentation: developing in-vitro methods and changing legislation.

Despite recent changes in legislation in several countries and general reduction in the use of animals in biomedical research, the impatience of antivivisectionists to see reductions in animal experimentation shows no signs of abating. Gerhard Zbinden analyses the reasons for this continuing dissatisfaction, arguing that real progress has been made in biomedical research, but that the complexities of developing internationally recognized regulations constitute a barrier to rapid change in product safety testing methods.

Animal Experimentation↗
PubMed1990

Effects of recombinant human alpha-interferon in a rodent cardiotoxicity model.

Recombinant human alpha-interferon infused intravenously into rats at doses of 10(6) (1st infusion) and 10(5) IU (2nd and 3rd infusion) produced marginal evidence of liver damage but no serious toxicity. During the 2nd and 3rd infusions an increased incidence of cardiac arrhythmias of various types was observed. In 2 rats electrocardiographic evidence of myocardial ischemia was noted. No changes in myocardial structure were demonstrated by light and electron microscopy. With the high dose the decrease in body temperature resulting from anesthesia was significantly reduced. Antibodies to interferon were demonstrated in the majority of the animals.

Animals↗
PubMed1990

Acute toxicity testing in the nonlethal dose range: a new approach.

A new modification of acute toxicity testing of chemicals in rats is presented. Instead of using death as the principal criterion of toxicity, it is based on a careful, standardized clinical assessment of toxic signs measured in the nonlethal dose range. Test compounds are administered to groups of rats at four dose levels, selected on the basis of pilot experiments. General indices of toxicity, i.e., body weight gain, food and water consumption, and body temperature, are recorded at regular intervals; activity in the home cage is monitored continuously with a newly developed passive infrared device; neurobehavioral dysfunctions are assessed repeatedly with a checklist; and routine hematology is done on the 4th day after administration of the test compounds. All measured signs of toxicity are scored in relation to the control groups so that the absolute magnitude of the score increases as a function of the deviation from the normal conditions of the animals. In order to take into consideration the course of intoxication and the rate of recovery, toxicity scores are added over the duration of the whole experiment. For each variable measured, the resulting total scores are converted into a relative point system, scaling from 0 to 10 points. These points are added to a single "total ToxScore" value for each dose group. A regression line is calculated for these total ToxScore points, and the dose giving 15 total ToxScore points is determined. Based on the results obtained with nine reference substances, a classification system is proposed that is comparable to that based on LD50 values. It is concluded that the proposed test procedure provides much more information on the signs of acute toxicity, the course of the intoxication, the slope of the dose-effect curve, and the rate of recovery than does the standard LD50 test. In addition, the degree of distress and suffering of the animals is reduced.

Acetanilides↗
PubMed1990

Safety evaluation of biotechnology products.

Preclinical safety studies with biotechnology products are not only performed for regulatory purposes, but should first and foremost provide information about the potential toxic effects in patients. The initial toxicological experience, using standard testing procedures developed for drugs of small molecular weight, often gave disappointing results, and the development of antibodies against the heterologous products cast doubt upon the validity of the testing approach. In order to assess the safety of new biotechnology products, compounds must be looked at on a case by case basis. Exaggerated pharmacodynamic effects are often responsible for the major toxicological problems. For some compounds, 'intrinsic toxicity', i.e. adverse effects due to the molecule per se, may play a role. With others, 'biological toxicity', i.e. the activation of physiological processes such as antigen-antibody interaction, release of mediators and cytokines, or initiation of the arachidonic acid-prostaglandin cascade, may be the cause of the observed adverse effects. Examples are given that show the importance of a good understanding of the biological mechanisms of action of toxicity observed in animals and in patients.

Animals↗
PubMed1989

Quantitative analysis of rat activity in the home cage by infrared monitoring. Application to the acute toxicity testing of acetanilide and phenylmercuric acetate.

A new method for continuous in-cage monitoring of the activity of rats using passive sensors to detect the animals' infrared emissions, and its usefulness for toxicological screening tests is described. In order to obtain baseline values for toxicological tests, the differences between day and night activity, adaptation to changing day/night rhythm, the effects of handling the animals (measurement of body weight, food and water consumption) and the effect on activity patterns of the female estrus cycle were investigated. In two separate experiments, single doses of acetanilide and phenylmercuric acetate were administered. Passive infrared monitoring of motor activity proved to be a sensitive and discriminating method suitable for quantitative and qualitative assessment of acute toxic effects.

Acetanilides↗
PubMed1989

Assessment of thrombogenic potential of liposomes.

The effects of liposomes with positive, neutral and negative surface charges on platelets and the plasmatic coagulation system were investigated in several in vitro and in vivo models. Negatively charged liposomes stimulated the plasmatic contact activating system as demonstrated by significant acceleration of whole blood clotting time measured in containers with nonwettable (siliconized) surface. The same liposomes induced reversible aggregates of human platelets in vitro and circulating reversible platelet aggregates after intravenous infusion in guinea pigs. Liposomes with positive and neutral surface charges had no effect on plasmatic coagulation and platelets. The biological mechanisms and the toxicological relevance of these findings are discussed.

Animals↗
PubMed1988

Interaction between ethanol and caffeine in operant behavior of rats.

The interaction between ethanol and caffeine on operant behavior was studied in 24 water-deprived male rats trained in a discrete trial spatial alternation schedule with water as reinforcer. One single drug dose-response experiment or one dose combination of ethanol and caffeine (including the associated control treatments) was run on 4 successive days in 1 week. The four treatments of 1 week were administered to each animal in a distinct order according to the 24 possible permutations. In the single drug weeks, ethanol (0.25, 0.5, 0.75 and 1.0 g/kg IP) or caffeine (5, 10, 20, and 40 mg/kg PO) were administered 15 min before the session. In four interaction experiments all combinations of two doses of ethanol (0.5 and 1.0 g/kg IP) and two doses of caffeine (25 and 50 mg/kg PO) were employed. Ethanol and caffeine alone showed both dose-dependently decreased choice accuracy and increased response latency and passiveness. In combination, caffeine normalized the ethanol-induced alterations in ITI response rate and pause length but potentiated the effects on choice accuracy, latency and number of pauses. The results are interpreted in terms of effects of these drugs on attentional and arousal processes, and the test procedure is proposed as a screening tool for the preclinical assessment of ethanol-drug interactions.

Animals↗
PubMed1988

Nephrotoxicity screening in rats; general approach and establishment of test criteria.

The concept of a nephrotoxicity screening test that is based on quantitative assessment of urine collected under standardized conditions for 15.5 h is presented. One to eight urine collections were performed in large numbers of untreated female Sprague-Dawley rats. Normal values for water consumption, urine volume, pH, and excretion of protein, gamma-glutamyltranspeptidase, malate dehydrogenase, electrolytes, glucose, amino acids, leukocytes, erythrocytes, epithelia, unspecified cells and cylinders were determined. Test criteria were established based on the statistical distribution of these measurements. In rats repeatedly placed in metabolism cages, a statistically significant decrease in leukocyte excretion and an increase in excretion of epithelia and unspecified cells were observed. All other variables did not change with time.

Animals↗