Изв. Нац. академии наук Беларуси, Сер. мед.-биол. наук, 2001, No.1

Изв. Нац. академии наук Беларуси, Сер. мед.-биол. наук, 2001, No.1

Известия Национальной академии наук Беларуси
СЕРИЯ МЕДИКО-БИОЛОГИЧЕСКИХ НАУК
Издатель Беларуская навука, Минск, Республика Беларусь

Number 1, 2001

СОДЕРЖАНИЕ

Gourine V. N.
Greetings to authors of the Journal. p. 5

PHYSIOLOGY AND GENERAL PATHOLOGY

Sudakov K. V., Umrukhin F. E.
The c-fos gene expression during emotional stress in rats: effects of delta-sleep inducing peptide and ACTH fragment. pp. 6--14

Summary: The data obtained indicate that preliminary application of delta-sleep inducing peptides increase the c-fos gene expression in normal rats, whereas the same oligopeptides inhibit the expression of early c-fos gene, induced by emotional stress. A changed response of the c-fos gene to the peptides in the parvocellular paraventricular hypothalamus and in the medial and lateral septum after stress exposures may be accounted for by an altered reception of these substances in these brain structures during emotional stress. However, the effect is not observed in the basolateral amygdala. The intimate mechanism of influence of the given regulatory peptides on the c-fos gene expression in the brain structures remains quite unclear and needs further research.

Nichelmann M., Janke O., Hochel J., Tzschentke B.
Development of physiological control systems in avian embryos. pp. 15--25

Summary: During the last 6 years we have investigated the embryonic development of the following control elements, controlled variables or other parts of the physiological control systems in precocial avian species: oxygen consumption, heart rate, respiratory rate, chorioallantoic blood flow, endothermy, hypothalamic thermosensitivity, autonomic nervous system, hearing, and circadian rhythmicity. Besides the special results published elsewhere, some general conclusions concerning the mechanisms of functional embryonic development may be formulated in the following thesis: 1. During the early ontogeny adaptive body functions are developed before they are immediately necessary for the survival of the organism. Possibly, they will be induced by developmental processes in the brain and in the periphery. The activation of peripheral organs has also an influence on brain development via feed back loops; there are very important interrelationships between the brain and peripheral organs which stimulate the organ function and the activity of the central mechanisms reciprocally. Prenatal activation of some functional systems may have a training effect on their postnatal efficiency. 2. The development of physiological control systems starts with non-coordinated and immediately non-adaptive reactions. In this respect not the direction of changes in the activity of body functions seems to be most important, but only the fact that these changes do occur. 3. Besides the genetically determined adaptation of the organism to the environment, epigenetic adaptation processes occur. Generally, most of these functional systems, such as temperature control, are open loop systems until a defined time. Later, mostly prenatally, the systems develop feed back and closed control systems occur. As a rule, the actual value during the determination period has a very strong influence on the set-point of the system.

Tzschentke B., Basta D., Nichelmann M.
Epigenetic temperature adaptation in birds: peculiarities and similarities in comparison to acclimation. pp. 26--31

Summary: Epigenetic temperature adaptation can be induced by prenatally applied temperature changes and in birds by changing the incubation temperature. In 1- to-10-d-old Muscovy ducklings and turkeys the influence of low (34.5/35°C), moderate (37.5°C control) and high (38.5°C) incubation temperature during the last week before hatching on postnatal development of heat production, colonic temperature, preferred ambient temperature and hypothalamic neuronal thermosensitivity was investigated. The results show that prenatal cold load induces postnatal cold acclimation and prenatal heat load postnatal heat acclimation. For instance, in cold incubated ducklings already at the 1st day post-hatching the heat production at a low ambient temperature (10°C) was 56% higher than in the control and these birds were able to keep their body temperature on a higher level under cold conditions (39.5 ± l.l°C cold incubated birds, 37.5 ± 2.9°C control). During the first 10 days of life the preferred ambient temperature in cold incubated ducklings was lower and in warm incubated turkeys it was higher than in the control group. On the cellular level (hypothalamic neuronal thermosensitivity) in the brain, in 10-d-old ducklings a low incubation temperature induced an increase and a high incubation temperature a decrease in total hypothalamic warm-sensitivity in relation to the control. In comparison with postnatal acclimation we have shown that epigenetic temperature adaptation might induce similar alterations in postnatal temperature regulation. Obviously, the peculiarity of epigenetic temperature adaptation is that this process occurs during early pre- or postnatal ontogeny in short time-windows (sensible phases) only. In such sensible phases control systems like the thermoregulatory system might be life-long determined or imprinted by various internal and/or external (epigenetic) factors.

Kulchitsky V. A., Kulchitsky S. V., Netukova N. I., Ekimova I. V., Hornet N. A., Pesotskaya Ya. A.
Structural changes in the brainstem of vagotomized rats are accompanied by disturbances of the pain sensitivity control during endotoxemia. pp. 32--37

Summary: The aim of the work was to clarify the functional impact of structural alterations in the brainstem of subdiaphragmatic vagotomy rats for the pattern of the nociceptive and temperature responses to endotoxin. Experiments were performed in 49 loosely restrained male Wistar rats. Four weeks before experimentation subdiaphragmatic truncal or sham vagotomy were made. Five days before, a silicon catheter was intraperitoneally implanted. On the day of the experiment the animals received endotoxin (3 µg/kg LPS, i. p.) or pyrogen-free saline. Colonic temperature was measured with a thermocouple. Changes in nociception were assessed by the tail-flick latency to a noxious heat stimulus. At 75 min after LPS the vagotomized rats showed hyperalgesia and fever, as well as a decreased activity of lactate and succinate dehydrogenases in neurons of the median preoptic and supraoptic nuclei (MnPO and SO) as compared with saline treated animals. There was no hyperalgesia and fever in response to LPS in vagotomized rats. Also, LPS induced a significantly smaller (P < 0.05) decrease in the activity of lactate dehydrogenase in MnPO and SO neurons of vagotomized rats as compared with sham operated animals. Using electron microscopy, marked alterations in neurons of the solitary tract nucleus, indicating destructive processes in the brainstem, were found 4 weeks after vagotomy. It is suggested that structural changes in the caudal brainstem (solitary tract nucleus) of vagotomized animals are one of the causes of disturbances of associated responses of neurons in other parts of the CNS (at the hypothalamic level, in particular) and a disorder of complex systemic response to endotoxin which includes the nociceptive and temperature responses.

Medvedev V. I.
Some features of the placebo effect. pp. 38--40

Summary: An attempt is made to explain the placebo effect as a form of operative rest. A number of cardiovascular changes is shown to indicate the preparedness of the body for physical activity, which is the essence of operative rest.

Vismont F. I., Shust O. G.
Involvement of the detoxication function of the liver and blood a₁-antitrypsin in the mechanisms of endotoxin fever development. pp. 41--48

Summary: In experiments on rats and rabbits it was found that inhibition of the functional activity of the liver and its detoxication function by CCl₄, accompanied by a decreasing level of a₁-antitrypsin in blood, impairs the development of characteristic thermoregulatory response of the organism to pyrogenal and prevents febrile development. Manifestation of the changes in heat exchange processes and body temperature to endotoxin was shown to depend on the functional activity of the liver and its detoxication function. The same dosage of endotoxin may increase the body temperature, fail to influence it or lead to hypothermia. Convincing evidence for a pyretic action of a₁-antitrypsin was obtained, indicating the importance of the blood content of a₁-antitrypsin for the pathogenesis of endotoxin febrile response.

Degtyarev Yu. G., Semenenya I. N.
The state of the functional system of the organism during experimental cholestasis. pp. 49--50

Summary: The functional state of the thermoregulatory, circulatory and nociceptive systems was studied on a model of extra hepatic cholestasis in male Wistar rats. Possible mechanisms of the revealed changes are discussed.

NEUROMORPHOLOGY AND NEUROCHEMISTRY

Rudenok V. V.
Distribution of neuropeptides in human sympathetic ganglia. pp. 51--53

Summary: Vasoactive intestinal polypeptide (VIP) -- and calcitonin gene-related peptide (CGRP) -- immunoreactive nerve cells and fibres were demonstrated in human lumbar sympathetic ganglia by indirect immunocytochemistry. The evidence for the presence of VIP and CGRP in human paravertebral ganglia suggests a neurotransmitter heterogeneity of human sympathetic ganglia and involvement of the peptides in age-dependent regulation of target-organ function.

BIOCHEMISTRY AND ENDOCRINOLOGY

Nikandrov V. N., Pyzhova N. S.
Oxygen-dependent pathway of plasminogen activation and new physico-chemical mechanisms of proteolysis. pp. 54--60

Summary: The results of the study of active oxygen species (superoxide radical) participation in the plasminogen-activating function of streptokinase were analyzed. The possibility of such species participation in the activation of a number of proteinase zymogens and in proteinase catalytic function was considered. A concept of oxygen-dependent pathway of plasminogen activation, a hypothesis of oxygen-dependent proteolysis and applied aspects of this problem were stated.

Moiseenok A. G., Rezyapkin V. I., Gurinovich V. A., Omel'yanchik S. N.
Dephospho-CoA is the main component of intracellular CoA turnover in mammalian liver. pp. 61--64

Summary: Parenteral injections of [¹⁴C]-pantothenate sodium in a dose corresponding to the daily requirements during 10 days to young albino rats which had been given synthetic meal with or without the vitamin for 8 weeks led to a significant accumulation of products of the radionuclide biotransfomiation in the liver and its mitochondrial compartment. By HPLC technique, the metabolites were identified as CoA (the main component), pantothenate+phospho-pantothenate, phospho-pantetheine, dephospho-CoA (it made up to 11% of CoA precursors in liver homogenates from naive and vitamin-lacking animals). In liver mitochondria the radioactive dephospho-CoA amount (relative to the CoA fraction) was 26% in the rats with vitamin deficiency and 166% in the animals with normal level of the vitamin. We suggest that dephospho-CoA is the dominant biosynthetic and (or) transport form which provides intramitochondrial CoA stock.

PHARMACOLOGY AND TOXICOLOGY

Losev N. A.
Interaction between m- and n-cholinoreactive systems: a further development of S.V.Anichkov's ideas. pp. 65--69

Summary: This is a brief review of the autnor's studies which develop the S.V.Anichkov's ideas. A concept is set up and experimentally substantiated that the cholinergic transmitter system is the basal one (relative to other transmitter systems) which regulates the somatic, autonomic, hormonal, immune, mnestic and other body functions. Normal functioning of this basal system is conditioned by an optimum of the reciprocal interaction of its m- and n-cholinergic mechanisms. The paper presents a new approach to highly efficient pharmacological correction of a number of persistent pathological states of the organism by combination of m-cholinergic blockade with simultaneous n-cholinergic stimulation and n-cholinergic blockade with stimulation of m-cholinergic mechanisms, as well as states a necessity of further search for new substances which might selectively influence n- and m-cholinoreceptors.

VIRUSOLOGY, MICROBIOLOGY AND IMMUNOLOGY

Kuzmitsky B. B., Konoplya N. A., Golubeva M. B., Koroleva E. V., Lyubin G. S.
Effect of prostaglandin analogues of 11-desoxy-E and F_a series, having additional heterocycle in w-chain, on polyclonal lymphocyte activation. pp. 70--73

Summary: Prostaglandins of 11-desoxy PGE and PGF_a series obtained by complete synthesis methods enhance lymphocyte polyclonal activation in case of their administration per os at doses of 1-5 µg/kg, 9_a-hydroxyprostanoid with native carbmethoxyalkylic a-chain being 2-2.5 times more effective than the 9-ketofunction containing analogue. In a model of primary immune response to sheep red blood cells (SRBS) these compounds enhanced, in a dose-dependent fashion, humoral immunity, which was demonstrated by a 2.5-fold increase in the accumulation of IgM-synthesizing antibody forming cells in the spleen of male and female CBA mice. There was a strict correlation between this phenomenon and an increase in the level of hemagglutinin titers registered in the blood serum of the mice. The immunity stimulation depended on the extent of antigenic load and was maximal in case that the mice were immunized intraperitoneally with 1.5 • 10⁷ SRBS per mouse. Administration of the compounds under study was shown to cause a sufficient stimulation of the immune response to lipopolysaccharide E. coli used as B-dependent antigen.

BIOPHYSICS AND BIOMEDICAL TECHNOLOGIES

Cherenkevich S. N., Semenkova G. N., Kovalenko E. I., Smirnova E. N.
Generation of reactive oxygen species by neutrophils in children with hematoblastosis. pp. 74--78

Summary: The mechanisms of the reactive oxygen species (ROS) generation by neutrophils of children with non-Hodgkin's lymphomas and acute lymphoblastic leukemia were studied by the method of luminol dependent chemiluminescence. The oxygen activating ability of neutrophils, myeloperoxidase activity in the cells and secretion of myeloperoxidase were shown to decrease at neutropenia induced by intensive chemotherapy of the patients. Treatment with G-CSF led in most cases to an increased capacity of neutrophils to generate ROS. Application of G-CSF was accompanied by changes in the arachidonic acid metabolism and redistribution of 5'-lipoxygenase and cyclooxygenase contribution to processes related to the ROS formation.

Beloyenko E. D., Kupchinov B. I., Slobozhanina E. I., Yermakov S. F., Rodnenkov V. G., Korlova N. M., Acemont O. L.
The liquid-crystalline state of the joint oil. pp. 79--85

Summary: This investigation is dedicated to a natural phenomenon -- anomalous low friction of living joints. The experiments revealed a previously unknown property of synovial fluid, namely, that liquid-crystalline cholesterol compounds are present in joint lubricant and liquid-crystalline nematic phase within physiological temperatures is formed. It is suggested that the liquid-crystalline phase in synovia can reduce friction of the contacting cartilages. Methods of physical and chemical analysis and tribological testing of natural and pseudosynovial fluids were used.

REVIEWS

Gourine V. N.
Disinhibition of brainstem pacemakers and its significance for the interaction of the nervous centres. pp. 86--95

Summary: The paper briefly analyzes the current state of the problem and substantiates a special role of disinhibition in the reflex activity of the brainstem centres. According to the author's concept, pacemakers of this CNS region can be disinhibited by signals from peripheral receptors. The main feature of relations between them and pacemakers is that disinhibitory and excitatory pathways operate separately of each other. Putative relations between disinhibitory and excitatory inputs on brainstem pacemakers are represented by a formula which also shows a possibility of summation of disinhibitory influences of different centres. The proposed neuronal models of the thermoregulatory centres, including disinhibitory links, allow to account for manifestations of the central action of synaptically active substances (GABA and others). The functioning of disinhibitory mechanisms as links between the centres of different functional systems provides trophic interactions of these centres. Disturbances of such interactions, and mainly the crossing inhibition mechanisms, must be distinguished as a specific form of the pathology of the nervous system. Recognizing the existence of such disturbances of integrative processes (genetic and acquired) in the brainstem structures necessitates investigation of their neuronal and molecular mechanisms.

Sapronov N. S., Fedotova Yu. O.
Neurotropic factors and thyroid hormones. pp. 96--101

Summary: In this review the authors analyze the current concepts of the mechanisms of action, functional activity, and interactions of neurotrophins and thyroid hormones in the organism. Thyroid hormones regulate versatile aspects of the brain maturation by controlling the expression of a limited number of the key genes which are supposed to be genes of neurotrophic factors. These genes are able, in their turn, to regulate the expression or activity of other genes in cell populations, responsible for the differentiation and functional activity of CNS neurons throughout the period of development.

Votyakov V. I., Eremin V. F., Titov L. P., Amvrosjeva T. V.
The existence of the global natural focus of HIV infection: ahypothesis. pp. 102--109

Summary: The paper presents scientifically substantiated data on the origin of HIV from monkeys inhabiting the forests of equatorial and subequatorial Africa. A hypothesis is proposed of the existence of the natural source of HIV infection in sub-Saharan countries.

Reshetnyak V. K., Kukushkin M. L.
The pathophysiology of pain. pp. 110--116

Summary: The review describes the neurophysiological and neurochemical mechanisms underlying different types of pathological pain. Features of clinical manifestations of somatogenic and neurogenic pain are considered. Pathogenetically substantiated methods of treatment of different chronic pain syndromes are discussed.

Gourine A. V., Gourine V. N., Klyuger M. D.
Role of protease inhibitors in fever a brief review. pp. 117--120

Summary: Considerable evidence accumulated indicates that plasma protease inhibitors such as a₁-antitrypsin (a₁A) and a₂-macroglobulin (a₂M) may play an important role in endotoxin-induced fever and cytokine responses. We have shown that: (i) protease inhibitors a a₁A and a₂M induce fever in rats and mice when injected in amounts similar to those observed during the development of the acute phase response; (ii) a₁A and a₂M induce a rise in plasma concentrations of pyrogenic cytokines interleukin-6 (IL-6) and tumor necrosis factor-a (TNFa) in mice; (iii) a₁A and a₂M induce production of IL-6 and TNFa by rat blood mononuclear cells in vitro, (iv) a₂M gene knockout mice develop a short-lasting and markedly attenuated fever in response to endotoxin compared with their wild-type counterparts; (v) during fever, plasma concentration of TNF-a is significantly lower in the a₂M knockout mice compared with their wild-type controls. The data support the hypothesis that protease inhibitors are essential for the normal development of endotoxin-induced fever and cytokine responses. The results also indicate that a putative mechanism of protease inhibitors involvement in fever is through the regulation of cytokine production and/or clearance.

ANNIVERSARIES

Vladimir Alexandrovich Matyukhin (On the 70th anniversary). pp. 121--123

Summary: On June 11.2001, will be the 70th anniversary of V. A. Matukhin, well known scientist in the field of climatic physiology, bioenergetics, chronophysiology, biorhytmology and radiation medicine. V. A. Matukhin studied at Chelyabinsk and Kiev Medical Institutes and at the Naval Department of Leningrad Medical Institute which he graduated in 1953. In 1958 -- PhD, in 1965 -- Dr. Sci. Professor since 1977. Academician of Academy of Medical Sciences of the USSR since 1986, and Academician of National Academy of Sciences of Belarus since 1995. He published 8 monographs and over 200 articles. Supervisor of 5 Dr. Sci. And 17 PhD. V. A. Matukhin is interesting and erudite to talk to, a friendly person, and is held in esteem by Belarus's scientists who wish him new creative achievements.
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