Publications by authors named "Zbinden G"

Unlabelled: A longitudinal field experiment was carried out over a period of 2 weeks to examine the influence of product aesthetics and inherent product usability. A 2 × 2 × 3 mixed design was used in the study, with product aesthetics (high/low) and usability (high/low) being manipulated as between-subjects variables and exposure time as a repeated-measures variable (three levels). A sample of 60 mobile phone users was tested during a multiple-session usability test.

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In viral diseases of the CNS, both interferon-alpha/beta and interferon-gamma are produced intrathecally. At least some of the neurological symptoms associated with these diseases may be due to the effects of these cytokines. We have studied the actions of interferons on CA3 pyramidal cells in hippocampal slice cultures.

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The multispecies approach in toxicity testing was originally motivated by the frequent findings of species differences in responsiveness to the pharmacological and acute toxic effects of chemicals. When the guidelines for repeated-dose toxicity experiments were developed in the early 1940s, the concept of using several species of animals was automatically included without careful scientific validation. In response to demands from the U.

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Although insoluble bismuth (Bi) salts are known to be neurotoxic, recently interest in oral Bi therapy has been renewed because of encouraging results obtained in the treatment of gastritis and peptic ulcer associated with Helicobacter pylori infection. For risk assessment of orally administered Bi preparations it is important to determine the minimal neurotoxic Bi concentration in the brain. This concentration was determined in cultures of brain, meninges and neuronal retina cells from embryonic chicks and in cultures of hippocampal slices from rats.

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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.

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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.

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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.

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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.

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Alternative methods are already widely used in fundamental biological research. Among 6,649 papers given at the FASEB 1989 meeting, nearly 60 p. 100 deal with experimental data obtained without the use of live animals.

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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.

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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.

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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.

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[Neurobehavioral toxicology].

Farmakol Toksikol

December 1989

The various experimental approaches to detect and characterize neurotoxic chemicals, i.e. pathomorphology, electrophysiology, neurobiochemistry and ethology, are discussed.

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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.

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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.

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The reasons reduction and replacement of laboratory animals are advancing rapidly in basic biomedical research, and why in industrial toxicology progress is much slower, are analyzed. Reference is made to a previous report from our laboratory, and the general concept of the program is outlined. Encouraging developments concerning acceptance of new concepts in acute toxicity testing by various regulatory agencies are reviewed (OECD, IKS, EEC, and Bureau of Pharmaceutical Affairs, Ministry of Health and Welfare, Japan).

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