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Biomedical subjects

S Trojan

Publications and source records attributed to S Trojan.

At least 37 records · Page 2Linked to original sources

[Regulation of receptor functions in the CNS].

The basic condition of life is capability to adapt not only to external but also to internal milieu conditions. I.e. receptors are able to change the intensity of signal transduction from the extracellular to the intracellular compartment in a short period. In a specific manner it concerns all receptor structures, both if they are located in cytoplasm or within the membrane. This review concentrates to the mechanisms existing in G protein-coupled receptors. Those protein structures can undergo a homologous or heterologous regulation. Homologous regulation means that only the properties of a receptor system influenced via extracellular signalling are changed. Heterologous regulation means, that receptor properties are changed despite that the extracellular signalling did not influence the receptor. It is possible to consider such changes as one of the level o homeostasis. Both homologous and heterologous regulations are essential for many physiological and pathophysiological processes. The most important examples of these processes, especially in the central nervous system, are reviewed here.

Animals↗

[Pathophysiology and clinical aspects of brain edema].

Brain oedema is defined as an abnormal accumulation of fluid in the brain tissue accompanied by an increased volume of the brain. It results in the intracranial hypertension directly endangering the patient's life. No causal treatment of the brain oedema is known at present. The brain oedema is not a disease, but it is a symptom of various clinical states. That is why experimental studies of its pathophysiology become the centre of attention. Though the classification of brain oedema according to the pathogenesis is still used (the vasogenic type--resulting from the increased permeability of blood-brain barrier; the cytotoxic type--caused by the cell metabolism impairment), recent papers has shown a definite retraction from such categorisation. It has been shown that neither type of brain oedema comes alone, but both can occur simultaneously during the development of the pathological state of the brain. The most important appears to be the primary insult. It affects the state of blood-brain barrier and brings about the vasogenic extracellular oedema or it can influence the cell metabolism with subsequent cytotoxic, cellular oedema. Categorisation of oedema into extracellular and cellular reflects more precisely the impairment of the homeostasis of the internal environment of the brain. Contemporary view on the classification and pathophysiological mechanisms of the brain oedema is discussed in our review.

Brain Edema↗

Model of spike propagation reliability along the myelinated axon corrupted by axonal intrinsic noise sources.

We investigated how selected electromorphological parameters of myelinated axons influence the preservation of interspike intervals when the propagation of action potentials is corrupted by axonal intrinsic noise. Hereby we tried to determine how the intrinsic axonal noise influences the performance of axons serving as carriers for temporal coding. The strategy of this coding supposes that interspike intervals presented to higher order neurons would minimally be deprived of information included in interspike intervals at the axonal initial segment. Our experiments were conducted using a computer model of the myelinated axon constructed in a software environment GENESIS (GEneral NEural SImulation System). We varied the axonal diameter, myelin sheath thickness, axonal length, stimulation current and channel distribution to determine how these parameters influence the role of noise in spike propagation and hence in preserving the interspike intervals. Our results, expressed as the standard deviation of spike travel times, showed that by stimulating the axons with regular rectangular pulses the interspike intervals were preserved with a microsecond accuracy. Stimulation with pulses imitating postsynaptic currents, greater changes of interspike intervals were found, but the influence of implemented noise on the jitter of interspike intervals was approximately the same.

Action Potentials↗

Model of spike propagation reliability along the myelinated axon corrupted by axonal intrinsic noise sources.

We investigated how selected electromorphological parameters of myelinated axons influence the preservation of interspike intervals when the propagation of action potentials is corrupted by axonal intrinsic noise. Hereby we tried to determine how the intrinsic axonal noise influences the performance of axons serving as carriers for temporal coding. The strategy of this coding supposes that interspike intervals presented to higher order neurons would minimally be deprived of information included in interspike intervals at the axonal initial segment. Our experiments were conducted using a computer model of the myelinated axon constructed in a software environment GENESIS (GEneral NEural SImulation System). We varied the axonal diameter, myelin sheath thickness, axonal length, stimulation current and channel distribution to determine how these parameters influence the role of noise in spike propagation and hence in preserving the interspike intervals. Our results, expressed as the standard deviation of spike travel times, showed that by stimulating the axons with regular rectangular pulses the interspike intervals were preserved with a microsecond accuracy. Stimulating the axons with pulses imitating postsynaptic currents, greater changes of interspike intervals were found, but the influence of implemented noise on the jitter of interspike intervals was approximately the same.

Action Potentials↗

Excitability changes of cortical neurons during the postnatal period in rats exposed to prenatal hypobaric hypoxia.

Pregnant rats were exposed to intermittent hypobaric hypoxia (at a simulated altitude of 7000 m or 5000 m) and the excitability of cortical neurons of their pups was tested. Stimulation of the sensorimotor cortex of rats prenatally exposed to hypoxia shortened the duration of cortical afterdischarges in 12-day-old rats, but did not change the excitability in 25-day-old animals. Shortening of the first afterdischarge in 35-day-old rats but the prolongation of the first afterdischarge in adult rats (as compared to the duration of cortical afterdischarges in rats not exposed to prenatal hypoxia) were registered. The possible mechanisms of different excitability of cortical neurons in rats prenatally exposed to hypobaric hypoxia are discussed.

Altitude↗

Carnitine pretreatment can partially change the excitability of the immature nervous tissue.

The possible protective action of L-carnitine on neuronal excitability was studied in 21-day-old male Wistar rats with implanted electrodes. Administration of L-carnitine did not change the elicitation and duration of the epileptic seizures (cortical afterdischarges, ADs) in rats under normobaric oxygen atmosphere conditions. However, in animals exposed to 30 min hypobaric hypoxia the duration of the ADs was shortened after the second, fourth and sixth stimulation (in comparison with the first evoked ADs) while carnitine-treated rats retained their neuronal excitability and the duration of ADs was shortened only after the third stimulation.

Animals↗

Muscarinic receptor subtypes in the heart--how many and why?

Muscarinic receptors are coupled to G proteins and to date, five subtypes have been characterized. These subtypes differ in their effects on second messenger production. Odd-numbered subtypes activate phospholipase C beta, and then they increase the production of inositoltrisphosphate and diacylglycerol. Even-numbered subtypes inhibit adenylylcyclase. The expression of individual subtypes is quite tissue specific. The heart tissue is realized as M2 predominant organ (in mammals; the muscarinic population in birds consist of M2 and M4 receptors). This article focuses on the possibility of existence of further muscarinic receptor subtypes in avian and mammalian heart in consequences with activation of phosphoinositid metabolism in the heart.

Animals↗

Perinatal complication: hypoxic-ischemic encephalopathy.

The favourable development of foetus is connected with the sufficient oxygen requirement. The brain of the foetus is extraordinarily sensitive to the disorders of oxygen supply. Ischemic brain injury connected with perinatal asfyxia is a frequent cause of hypoxic encephalopathy. An increased tolerance of the brain could be achieved by using peptide grows factors, inhibition of nitric oxide or modifying the glutamate receptors activity. Cerebral hypoxia evolves mainly in the case interruption of the feto-placental circulation or cardiorespiratory failure in the neonate. For making the diagnosis of neonatal encephalopathy is important to determine clinical neurological and systemic deragements in the first few days of life. Assessment of prognosis is generally based on a combination of clinical features and abnormalities of examination methods (electroencephalography, computer tomography).

Asphyxia Neonatorum↗

[Effect of a 10-day animal fat-free diet on cholesterol and glucose serum levels, blood pressure and body weight in 50-year-old volunteers].

The morbidity and mortality of cardiovascular diseases is high in developed countries including Czech Republic. The lifestyle decreases it in 50%. The aim of this work was to ascertain if the short lasting stay without stress and with vegetarian diet (without eggs) and physical activity is able to decrease the main risk factors of cardiovascular diseases. In 106 volunteers, mean age 49.1 (+/- 14.1) years, 83 women and 23 men, the body weight, blood pressure, serum cholesterol and blood glucose (Accutrend GC, Boehringer, Mannheim, BRD) have been measured before and after the stay at the same conditions. Eighty persons were healthy, seven persons with essential hypertension, eight persons with ischemic heart disease, four persons with diabetes mellitus and seven persons with other than cardiovascular diseases. In some persons the lipid spectrum was measured. Cholesterol decreased in blood serum from 4.9 to 4.3 mmol/l (11%--p < 0.01), blood glucose decreased from 4.2 to 3.3 mmol/l (p < 0.05), blood pressure systolic from 121.5 to 117.4 mm Hg (p < 0.01) and diastolic from 76.5 to 73.8 mm Hg (p < 0.05), body weight was not significantly changed. Our results showed, that 10-days lasting stay containing vegetarian diet and physical activity decreased the risk factors of cardiovascular diseases in 50 years-old volunteers.

Blood Glucose↗

Airborne gram-negative bacterial flora in animal houses.

The concentration and the species composition of airborne gram-negative bacteria were studied in four cattle houses, one pig house and one poultry barn. On average only between 0.02 and 5.2% of the total number of culturable aerobic bacteria were identified as gram-negative bacteria. Obligate anaerobic gram-negative bacteria were not isolated at all. In the airborne gram-negative bacterial flora the following bacterial families dominated: the Enterobacteriaceae, the Pseudomonadaceae and the Neisseriaceae. Within the family of the Enterobacteriaceae the species Escherichia coli and Enterobacter agglomerans were predominant. In animal houses using straw as bedding material Ent. agglomerans was most frequent, whereas in animal houses without litter E. coli was mainly found. Airborne Neisseriaceae were isolated very frequently in cow barns with Acinetobacter lowffii as the primary species. Airborne Pseudomonadaceae were found in high concentrations during periods of high air humidity. The results presented may also give some indications on the origin and sources of airborne endotoxins in animal housing.

Agricultural Workers' Diseases↗

Dehydrogenase activity in the blood and brain after adaptation to intermittent hypoxia.

Activities of LDH (lactate dehydrogenase) and alpha-HBDH (alpha-hydroxybutyric dehydrogenase) were measured in rats after intermittent exposure to the aerogenic hypoxia at a simulated altitude of 7000 m during the postnatal period (since birth to the 18th day) or in adulthood (older than the 90th day), except days 6, 7, 13, and 14 of the experiment. Enzymatic activity was measured using standard test kit (Biochemical Test Combination, Boehringer). Twenty hours after the last exposure to hypoxia, the activity of both enzymes was elevated in the serum and in the brain of the young rats. In contrast, in adult rats, the exposure to hypoxia did not result in changes of the enzyme activity in the serum or in the brain. Our results indicate that, whereas in adults the biochemical adaptation to repeated aerogenic hypoxia has no effects on the enzymatic activities of dehydrogenases, the same stimulus during the early postnatal period brings about rising of the aerobic glycolysis contribution to the total energy balance. Such increase is enabled by the increase of LDH and alpha-HBDH activities.

Adaptation, Physiological↗

Mechanisms of G-protein coupled receptor regulation.

It has been realized recently that the enhanced or lowered activation of a certain receptor type brings about changes not only in the sensitivity (or density) of this particular receptor type in cell membranes by producing its desensitization or sensitization, down- or up-regulation (i.e. homologous regulation), but also it could change the function (or density) of other receptors (cross-regulation). This review is focused on mechanisms of the homologous regulation (changes in the pathway activated by the appropriate type of receptor) and possible mechanisms of cross-regulation (changes in pathway activated by other type of receptor).

Down-Regulation↗

Effects of sinusoidal magnetic field on adherence inhibition of leucocytes: preliminary results.

The leucocyte surface properties manifest the cell-mediated immunity. The response of the cell-mediated immunity to external magnetic field was examined by observing leucocyte adherence to solid state surfaces. In the presence of antigen, leucocytes taken from cancer patients exhibit decreased adherence in contrast with adherence of leucocytes from healthy humans. After 1 h exposure to a sinusoidal magnetic field of 50 Hz and of 1 mT or 10 mT, adherence of leucocytes taken from cancer patients is strongly increased. The 1 mT magnetic field has stronger effect than the 10 mT field.

CD4-Positive T-Lymphocytes↗

Theoretical aspects of neuroplasticity.

The authors propose an integrative theory of the organization of neuroplastic processes. Neuroplasticity is assumed to be one of the essential characteristics of the nervous tissue which may be manifested comparatively rapidly and result in reversible changes (functional plasticity). It may also modulate the expression of genotype into phenotype (adaptation) and thus bring about long-lasting effects. Neuroplastic mechanisms are triggered by various natural or artificial stimuli, which may arise in the internal or external environment, and they may differ quantitatively or qualitatively. The effects of plasticity can lead to either positive or negative changes during development (evolutionary plasticity), after short-term exposition (reactive plasticity), after long-term or continuous stimuli (adaptational plasticity), and during functional or structural recovery of damaged neuronal circuits (reparation plasticity). Manifestations of plasticity have probably the same basis, irrespective of the cause which triggered them or the brain region where they were accomplished. Neuroplastic mechanisms are based on the modulation of signal transmission across synapses. They can be related to interneuronal relations. The resulting changes may occur in the communication between neurons (synaptic level), in the activity of local neuronal circuits (at the level of local circuits) or in the relations between individual functional brain systems (multimodular level).

Animals↗

[Regeneration and transplantation of nerve tissue].

Initial experimental transplantations and attempts to induce regeneration in the nerve tissue were done during the last decades of the 19th century. Though experiments were partly successful, the Cajal's doctrine about the unchanging adult nervous system overbalanced those promising findings for long period thereafter. Only during the last thirty years requirements of clinicians moved neuroscientists to study the problems of regeneration and transplantation in the CNS again. The possibility of transferring nerve cells from a donor to the host CNS, their survival, and formation of functional contacts has been fully established. Recent findings has shown that techniques of molecular biology can overcome some of the essential problems of transplantation, e.g. the glial scar. It is evident that the key role in plastic processes accompanying integration of the transplanted cells have neurotrophic factors produced both by the host and the graft. The entire microenvironment within the transplanted tissue is altered. Some specific features of the graft may be also significant. As the implant is mostly an embryonic tissue, processes of differentiation have to be considered. Accordingly, transplantation can be used as a model in the studies of neuroontogeny. In our experiments structural association of neurones transplanted as a suspension of embryonic cells into the dorsal blade of the dentate gyrus where granule cells were eliminated was described. Differentiation and signs of synapse formation were observed. Using Timm staining method, changes in the distribution of mossy fibres were identified. In thirty-day-old grafts, high number of NADPH-d positive neurones was found. Some nitric oxide producing neurones formed long processes extending into the host tissue. Such long fibres also produced nitric oxide synthase. In order to influence the process of the graft integration we induced extreme hyperfunction by a metrazol kindling. In kindled animals, more neurones survived, however, the density of apoptotic cells was similar to control animals. Our findings may be related to the hyperfunction or to the effect of metrazol on the nerve cells of both the host and the graft. They may result from microenvironmental changes or from the activation of genes participating on the mechanism of priming.

Animals↗

Is the identification of antibodies against the nervous tissue an indicator of brain injury?

Using a modification of the ELISA method, auto-antibodies against the own nervous tissue have been identified in the serum of laboratory rats. The prevalence of the IgM class of antibodies suggests their physiological significance. Antibody levels are higher in females than in males. Brain hypoxic injury brings about a shift in the spectrum of antibodies towards the IgG class. It may thus serve as an indicator of brain impairment caused by a lack of oxygen.

Animals↗

Heterologous regulation of muscarinic and beta-adrenergic receptors in rat cardiomyocytes in culture.

Previous work indicated that hyperstimulation of muscarinic receptors brings about profound changes not only in the density of the muscarinic receptors, but also of the beta-adrenoceptors in rat heart atria in vivo. We have now investigated whether a similar receptor cross-regulation occurs in cardiomyocytes in vitro. Cardiomyocytes from 3-4 day old rats were exposed to chemical agents on days 5-6 in culture. Densities of muscarinic and beta-adrenergic receptors were measured according to the binding of N-[3H]methylscopolamine and [ H]CGP 12177, respectively, to cell surface membranes and cell homogenates. Exposure of cells to the muscarinic agonist carbachol (1 mmol/l) brought about a profound decrease in the number of muscarinic receptors. The number of beta-adrenoceptors displayed biphasic changes, being augmented after 24 h (by 20-45% on the cell surface and by 29% in the homogenate) and diminished after 48 h and 72 h (after 48 h, decrease by 44-75% on the cell surface and by 36% in the homogenate). These effects of carbachol were not prevented by dimethylaminopropyl-bis-indolylmaleimide, the inhibitor of protein kinase C. Exposure of cells to the beta-adrenoceptor agonist isoprenaline (0.1 mmol/l) strongly diminished the number of beta-adrenoceptors on the cell surface and in the homogenate. The density of muscarinic receptors on the cell surface was diminished by 24-43% after 24 h exposure to isoprenaline and unchanged after 48 h, whereas the concentration of muscarinic receptors in the homogenate was unchanged after 24 h and increased by 20% after 48 h. The isoprenaline-induced decrease in the density of cell surface muscarinic receptors could not be simulated by forskolin and was not abolished by the protein kinase A inhibitors Rp-cAMPS and HA-1004. Dibutyryl cyclic AMP diminished the density of cell surface muscarinic receptors more than that of the beta-adrenergic receptors. Our data reveal a novel phenomenon of a biphasic change (an increase followed by a loss) in the density of beta-adrenoceptors during exposure of cardiocytes to carbachol. Activation of beta-adrenoceptors brings about less conspicuous changes in the density of muscarinic receptors. The observed phenomena of receptor cross-regulation cannot be explained by simple activations of protein kinases A and C.

Adrenergic beta-Agonists↗