Diabetes, from the Origins of the Problem to the Nobel Prize. Bioethics.

Analysis of scientific works from the creation of an experimental model of diabetes before discovery insulin was done. Emphasized is the priority of the Russian pathologist L. W. Sobolew (1876-1919) in the discovery of the endocrine function of the pancreas in experimental animals - rabbits, dogs, cats. In 1923 Canadian scientists Banting and Macleod were awarded the Nobel prize for the discovery of insulin. However, the methods and the idea of Nobel laureates were the same that had been developed 20 years earlier by the Russian scientists. Currently, the incidence of diabetes and related pathologies of organs and systems are growing. The use of animals in experimental biology and medicine will continue for the foreseeable future. The benefits to science and medicine derived from the use of animals in research are undeniable, but this process inevitably increases the responsibility of researchers. It is required constant work on improvement of the experimental methods in order to minimize pain, stress, and the number of animals used in the experiment.

[Ivan Solomonovich Beritashvili (1885-1974)--At the Origins of Cognitive Behaviorism].

Presents scientific creativity of I. S. Beritashvili in the cultural and historical aspect. The main attention is paid to the concept of figurative psychoneural activity of vertebrates. I. S. Beritashvili experimentally showed that the image of a vital object is fixed in memory and retrieved therefrom for the satisfaction of vital biological needs. The animal's behavior in such situations is governed not by material incentives, but by their images I. S. Beritashvili was one of the first, who connected figurative psychoneural activity with the brain morphology at the level of nerve cells. Stressed is the importance of the I. S. Beritashvili's concept for the development of evolutionary ethics and bioethics. The figurative of creative psychoneural activity in animals and humans, in fact, is the forerunner of modern cognitive behaviorism.

[Animal experiments and the major achievements in the history of biomedicine].

It is shown that major achievements in the history of biomedicine, obtained in experiments on animals: the discovery of blood circulation, the achievements of microbiology and development of the concept of immunity, the discovery of reflex and the doctrine of higher nervous activity, achievements of genetics, formation of modeling methods on animals and drug testing. It is stressed that the benefits for science and medicine, obtained through experimentation on animals, does not relieve scientists from responsibility.

[The system of assessment of the severity of ultrasound epilepsy in rats].

The method of induction of epileptic reactions in rats by ultrasound (24.3 kHz; 116dB) and the system of severity estimation of epileptic reaction was developed. Ultrasound--frequency above 20 kHz--absolutely silent for a person, may cause epileptic reaction in 3-9% of the rats. The possibility of using ultrasound--induced epilepsy in rats to evaluate anticonvulsant activity of drugs it is shown.

[Bioethics and biomedical experiment evolution from Alkmaion to Pavlov. Dedicated to 160 years since I.P. Pavlov's birthday].

Ethic aspects of biomedical experiment evolution from Alkmaion to Pavlov, are analysed. The history of reflexes in the paradigm of mechanitsism and antropomorphism is reinterpreted. It is emphasized that animal life and their behaviour exceed the bounds of mechanitsizm. It is grounded the necessity of humane treating living organisms. The theory of conditioned reflexes and the method of physiological synthesis are considered in the context of bioethics. It is shown that Pavlov's methodological approaches are in correspondence with the modern principles of bioethics of scientific animal experiments.

Development of resistance of an organism under various conditions of hypoxic preconditioning: role of the hypoxic period and reoxygenation.

Single exposure to moderate (10% O(2)) hypobaric, normobaric, and intermittent hypoxia is followed by a preconditioning response of the organism. The mechanisms for immediate adaptation are activated during the hypoxic period. Intermittent reoxygenation not only delays, but even suppresses this process. However, periods of oxygenation during the course of hypoxic training reduce the effect of hypoxia and prevent the possibility for "overdosage" of the adverse stimulus. Hence, they have a regulatory or normalizing role under these conditions. Our results indicate that hypoxitherapy in intermittent hypoxia mode provides optimum conditions for long-term adaptation.

[Minipigs as an object for medico-biological research].

The review considers the history of selection of minipigs convenient for maintenance in scientific laboratories. It is shown that minipigs are suitable for studies of wide range of problems and there are perspectives of their use for xenotransplantation. Problems of bioethics in connection with the appearance of new biomedical technologies are discussed.

[The experiments with laboratory animals from a bioethical point of view--history, modern time, perspectives]. / Rabota s laboratornymi zhivotnymi v kontekste bioétiki--istoria, sovremennost', perspektivy.

The origin of laboratory animal science was called forth by violent development of experimental biology and medicine in the XIX century on the one hand, and on the other hand by the necessity to have standard healthy animals for experiments with strictly definite biological characteristics. With this aim in view management technology and animal use in experiments have been constantly improved. "Laboratory animal" notion has been formed by the end of the XIX century. At the beginning of laboratory animal science development ethical problems were not as urgent as they are now. It is established that the three Rs bioethical conception of W.M.S. Russel and R.L. Burch (1959) has influence on modern state and perspectives of the development of animal experimental methods. It is shown that the existence of laboratory animal protection laws and the reflection in them of compulsory ethical review of scientific project and statistics of used laboratory animals is absolutely necessary.

[Methods for the euthanasia of experimental animals--the ethics, esthetics and personnel safety]. / Metody évtanazii éksperimental'nykh zhivotnykh--étika, éstetika, bezopasnost' personala.

In this paper there are shown chemical and physical methods of euthanasia of vertebrate animals. All methods are divided into three categories: A) Acceptable methods of euthanasia, B) methods acceptable only for unconscious animals, C) methods that are not acceptable for euthanasia. The acceptability or non-acceptability of the method is determined by ethic or aesthetic conceptions and also by conceptions of the personnel safety and the environment. There is provided a table of acceptable methods of euthanasia. Recommendations of working group of the Federation of Laboratory Animal Science Association (FELASA) were taken into consideration in this paper. The survey can be useful for the experimenters and personnel concerned with laboratory animals.

Ivan P. Pavlov's view on vivisection.

Pavlov's points of view on vivisection are analyzed and compared with the modern ethical conception of carrying out experiments on animals. It appears that Pavlov's points of view are largely in accordance with modern ethical requirements for experimenting on animals.

[I. P. Pavlov on animal experiments]. / I. P. Pavlov ob opytakh na zhivotnykh.

The paper is dedicated to the 150th anniversary of academician I.P. Pavlov's birthday. Pavlov's points of view on vivisection are analyzed and are compared with the modern conception of ethics of carrying out experiments on animals. It is discovered that Pavlov's points of view are in accordance with the key positions of modern requirements to ethics of experimenting on animals which are adopted in the world practice.

[I. P. Pavlov on vivisection and the modern ethical requirements for animal experiments]. / I. P. Pavlov o zhivosechenii i sovremennye éticheskie trebovaniia k éksperimentu na zhivotnykh.

It is shown that Pavlov's opinion is in agreement with the modern requirements for experiments in living animals: use of living animals in experiments is recommended only in the cases when there is no alternative and scientific-practical significance of the planned experiments is justified; minimization (as much as possible) of discomfort, distress and pain of animals under study without sacrifice of the quality of scientific research; use of appropriate number of animals necessary for obtaining reliable results which are adequate to a given experimental situation and general state of the animals inadmissibility of using extra number of animals; drawing up a protocol concerning the experimental procedure and results; reflection in the protocol the techniques of sedation, anesthesia, and euthanasia; constant care of the improvement of the theoretical and practical qualification of a researcher in the ethical questions and experimental technique. Pavlov's views led his time and at present they agree with modern concepts on the experimental ethics.

[The regulation of experiments on animals--ethics, legislation and alternatives]. / Reglamentatsiia éksperimentov na zhivotnykh--étika, zakonodatel'stva, al'ternativy.

Legislation and rules for animal experiments in many countries are proposed. Activities of international and national organizations, committees and administrative authorities are described. The importance of the three Rs principle and alternative methods for the humanization of bio-medical animal experiments are discussed.

[Lipid peroxidation in experimental myocardial infarct: the action of hyperbaric oxygenation]. / Perekisnoe okislenie lipidov pri éksperimental'nom infarkte miokarda: deistvie giperbaricheskoi oksigenatsii.

Rats with experimental myocardial infarction demonstrated decrease in the activity of superoxide dismutase and catalase and increase in the content of lipid peroxidation (LPO) products and Schiff bases both in and outside the area of necrosis. The combined ischemic damage and hyperbaric oxygenation resulted in the over additive effect of accumulation of LPO products in and outside the area of infarction. The data suggest that it is desirable to use antioxidants during hyperbaric oxygenation.

[Possible correction of the isoenzyme spectrum of lactate dehydrogenase in the developing rat brain in antenatal hypoxia]. / K vozmozhnosti korrektsii izofermentnogo spektra laktatdegidrogenazy razvivaiushchegosia mozga krys s antenatal'noi gipoksiei.

In ontogenesis (within 14 and 30 days of postnatal period) in brain cortex and medulla oblongata of rats the LDH isoenzyme spectrum was altered exhibiting an increase in LDH1 and a decrease in LDH5 content. Antenatal hypoxia caused a decrease in aerobic isoenzymes in brain cortex and an increase in their content in medulla oblongata. Nootropyl (pyracetame) corrected the LDH isoenzyme spectra in brain cortex of 14 days old rats and in medulla oblongata of 30 days old animals. The correction of the isoenzyme spectra was not observed in 30 days old animals.

[Role of lipid peroxidation in damage to serotonin receptors and development of epileptiform seizures during hyperoxia]. / Rol' perekisnogo okisleniia lipidov v povrezhdenii retseptorov serotonina i vozniknovenii épileptoformnykh sudorog pri giperoksii.

Hyperoxia brought about substantial accumulation of primary and end products of lipid peroxidation (LPO) and a significant lowering of alpha-tocopherol content in rat brain tissues. Preinjection of animals with synthetic and natural antioxidants (4-methyl-2,6-ditretbutylphenol and alpha-tocopherol) prevented LPO activation and decreased the frequency of epileptiform seizures induced by hyperoxia. Administration of a mixture of unsaturated fatty acids led to an opposite effect. The changes in the properties of serotonin receptors were found to be dependent on the hyperoxia-induced LPO. These changes were marked by the reduced specific binding of serotonin with neuronal membranes of the rat brain cortex. The data obtained allowed the conclusion about the key role played by LPO activation in toxic action of hyperbaric activation on the brain.

[Effect of nootropic agents on serum biochemical indices in intellectually deficient children]. / O vliianii nootropov na biokhimicheskie pokazateli syvorotki krovi u detei s intellektual'noi nedostatochnost'iu.

It was shown that a marked therapeutic effect or its absence in the piracetam and nootropil treatment of children with different degrees of mental retardation is largely determined by the presence in patients' metabolism (before treatment) of certain combined changes in the general activity of lactate dehydrogenase (LDH) and its isoenzymic spectrum with regard to the ratio between aerobic and anaerobic subunits. Experimental studies on rats support the necessity of taking into account patients' metabolism when prescribing nootropic agents. It is suggested that considering LDH changes (along with the clinical condition of patients) may be of prognostic significance in the efficacy assessment of treatment with nootropic drugs.