Physiologia Bohemoslovaca最新文献

The rate of delta mu H+ --induced erythrocyte Na+/H+ exchange is increased in both patients with essential hypertension (EH) and spontaneously hypertensive rats (SHR). The increase of Na+,K(+)-cotransport was revealed in erythrocytes of SHR only. This alteration as well as a decrease of mean cell volume were observed in both young and old erythrocytes of SHR. The moderate shrinkage of rat (but not human) erythrocytes results in an increase of the rate of Na+,K(+)-cotransport. The more pronounced shrinkage of rat (but not human) erythrocytes induces the Na+/H+ exchange. These reactions are accompanied by phosphoinositide response. Activator of protein kinase C (TPA) increases delta mu H+ --induced Na+/H+ exchange both in human and rat erythrocytes but it does not modify phosphoinositide metabolism. No differences were observed in the rate of Na+/H+ exchange between TPA-treated erythrocytes of SHR and WKY. We assume that the activation of protein kinase C increases Na+/H+ exchange in primary hypertension. Increased Na+/H(+)-cotransport revealed in an experimental model of primary hypertension is probably due to the decrease of erythrocyte volume.

In experiments on Wistar strain rats of both sexes, aged 5, 10 and 14 days and adult (90-120 days), of their own breed, the authors determined the quantitative proportion of individual fatty acids in the serum free non-esterified fatty acid (FFA) fraction, using mixed blood (obtained by decapitation) and the titration method of Trout et al. (1960). The proportion of the individual fatty acids was then determined in this fraction by gas chromatography (Base 1978) and their concentration (in mumol.1-1) was determined by simple calculation from the relative chromatogram data. Animals in the first three age groups were killed in the morning, directly from the nest; in adult rats the FFA fraction was measured after a 20 h fast. It was demonstrated that the increase in the proportion of monoenoic acids was highly statistically significant (about fivefold) during ontogenesis and that there was also a marked increase in the quantitative expression of polyenic acids, especially in group (n-6). The n-6/n-3 acid index in the FFA fraction altered during maturation (despite some fluctuation it basically rose from 4.3 in 5-day-old young to 10.0 in adult rats). It was further demonstrated that the concentration of fatty acids with a very short chain fell significantly during development, so that C 8:0, for example, could be detected only in the first two age groups, but not in 14-day-old and adult rats. The concentration of the saturated fatty acids C 15:0 to C 18:0 in the serum FFA fraction showed a statistically significant increase, while the index expressing the ratio of saturated to unsaturated fatty acids displayed a downward trend during development.

The anticonvulsant effects of two doses of clonazepam (CZP, Rivotril Roche, 0.1 and 1 mg/kg i.p.) were studied on model motor seizures induced by strychnine, bicuculline, 3-mercaptopropionic acid and metrazol in male laboratory rats (Wistar strain). In the first part the effects of different doses of the convulsants were investigated and for interaction with CZP doses were chosen after which more than 70% of the animals displayed generalized tonic-clonic convulsions (a grand mal seizure). Strychnine induced this type of seizure only: two doses (2 and 3 mg/kg s.c.) were used. CZP reduced the incidence of convulsions only after the larger dose, but plain solvent (propylene glycol, ethanol, water) was equally effective. The other substances first induced a seizure of minimal (mainly clonic) convulsions and only later a grand mal seizure. CZP was highly effective against bicuculline (3 mg/kg s.c.) and metrazol (100 mg/kg s.c.), but was less so against 3-mercaptopropionic acid. The effect on grand mal seizures was more pronounced in every case than on minimal seizures. The decisive role in the anticonvulsant effect of CZP is played by the mechanisms by which the convulsants induce epileptic manifestations. CZP is most effective against substances acting on the supramolecular complex GABA receptor (benzodiazepine receptor) chloride ionophore (bicuculline and probably metrazol).

The authors studied the effect of verapamil in 10(-7) to 10(-4) mol.l-1 concentration on the duration of action potentials (AP) and the corresponding isometric contractions (MG) from the right ventricular papillary muscles of adult guinea-pigs. In the steady state, using stimulation frequencies of 0.1, 1 and 2 Hz, verapamil caused dose- and use-dependent shortening of the AP plateau phase (D0) in 10(-5) and 10(-4) mol.l-1 concentration; lower concentrations did not affect the D0. With all the given concentrations, the MG fell in relation to the dose and the stimulation frequency. The pause regimen was defined by the induction of a steady state at 1 Hz frequency, followed by the interpolation of a pause lasting 5 s to 600 s and its effect was studied on the first and second AP after the pause and on the corresponding MG, without any pharmacological treatment and in the presence of verapamil (10(-5) mol.l-1). In the absence of the drug, slight lengthening of the D0 and weakening of the MG, proportional to the length of the pause, occurred after the pause. In the presence of verapamil, the first post-rest contraction after a 10 s pause attained five-fold the value in the steady state, while the second post-rest contraction was much weaker than the first. The possibility that verapamil acts on intracellular links in calcium metabolism, and of disproportion of its effect on the D0 and on contractility when it is administered in low concentrations, is discussed. The most likely mechanism of this effect is the presence of a negative feedback between calcium release from the sarcoplasmic reticulum and membrane electrogenesis.

Protein kinase C activity in the lysate of erythrocytes of patients with essential hypertension (EH) and spontaneously hypertensive rats (SHR) was found to be increased by 1.6-2.0 times as compared with normotensive controls. Membrane cytoskeleton alterations observed in the erythrocytes of patients with EH and SHR were revealed in decreased average erythrocyte volume, increase of cup-shaped cell formation, and increase of basal phosphorylation of band 4.9 protein. In addition, the rate of Na(+)-H+ exchange in erythrocytes of EH patients and SHR was increased by 1.9-fold. In vitro treatment of erythrocytes of healthy donors and Wistar-Kyoto rats (WKY) with protein kinase C activator (12-O-tetradecanoylphorbol-13-acetate) leads to similar changes of cell shape, cell volume, band 4.9 protein phosphorylation and Na(+)-H+ exchange, as well as to an increase of diS-C3-(5) fluorescence. It may be assumed that alterations of these parameters revealed in primary hypertension are caused by increased activity of protein kinase C.

One of the central issues in present experimental pain research is to establish the identity, location, and mechanism of action of various opioids (opioid peptides and alkaloids) and multiple opioid receptors in the modulation of nociceptive processes. At the cerebral level, studies employing several experimental approaches point to an essential role of beta-endorphin in analgesia, induced by electrical stimulation of the periaqueductal grey of the midbrain. Tolerance and cross-tolerance studies suggest that mu-opioid receptors mediate this effect. The significance of delta- and, in particular, chi-opioid receptors in cerebral pain modulation is less well documented. At the spinal level, nociception is relayed in the dorsal horn, where opioid peptides as well as all types of opioid receptors are abundant. mu-opioid receptor-mediated antinociceptive processes appear to be most important in this region, but delta-opioid receptors may also be involved. In addition, a role of chi-opioid receptors can be demonstrated under certain conditions. Recent experiments indicate that opioids may also modulate nociception in the periphery, in particular in inflamed tissue. The identification of opioid receptors and their endogenous ligands, the opioid peptides, marked the beginning of a new era in pain research. The differentiation of several types of opioid receptors and the subsequent characterization of a series of opioid peptides illustrate the striking complexity of opioid systems. The implications of this multiplicity for neurobiology in general and for the understanding of pain mechanisms in particular are presently not fully understood. In this presentation some aspects of opioidergic pain control at various levels of the neuraxis will be discussed.

Conditions allowing physiological development were determined in infant rats delivered by Caesarian section on the 22nd day of gestation and fed, from birth onwards, on various diets by stomach tube. Two new diets were prepared--K 50 A (11.7% fat, 7.7% protein) and LNaH (7.6% protein, 12% fat). The sole difference between the two diets is in the essential fatty acid (EFA) content, which is 42.6% in diet K 50 A, but only 0.7% in diet LNaH. Animals reared on the LNaH diet displayed slower growth and delayed development of the adenohypophysis and the thymus. Degenerative changes (intracytoplasmic vacuolation) were found in the somatotropin-producing cells of the adenohypophysis. The serum prolactin concentration of animals fed on the LNaH diet was lower than in the suckled controls and in animals given the K 50 A diet. The damaging effect of the LNaH diet was particularly marked on the first five days after birth, indicating that this is a critical period in the development of the newborn rat. The histological structure of the adenohypophysis and thymus of animals reared on the K 50 A diet was the same as in the suckled controls.

Female Wistar rats in experimental groups were treated subcutaneously with a single dose of 0.02, 0.04, 0.06 or 0.08 mmol CdCl2.kg-1 body weight. Superovulated oocytes were cultivated in vitro for 4 or 14 h up to the stage of germinal vesicle breakdown (GVBD) and metaphase II (M II). In all, 606 oocytes were used for the determination obtained document that the Cd content in oocytes of cadmium-treated rats increases from less than 0.1, 1.6 +/- 0.4, 2.8 +/- 0.5, 6.5 +/- 0.3, 10.8 +/- 0.2 pg per oocyte. With and increasing cadmium dose the percentage of oocytes which reached the stage of metaphase II after 14 h of cultivation in vitro, decreased (86.6%, 77.6%, 43%, 4.3% respectively).

125I-labelled Fab antidigitalis antibodies were administered i.p. to rats, whose organs were removed 20 h later and examined for radioactivity. Maximum radioactivity was found in the thyroid region, followed by the kidneys, liver, adrenals, heart, skeletal muscle and brain. The radioactivity of kidneys was greater than in any of the other organs except the thyroid, where it probably resulted from the uptake of radioiodine, released from the antibodies. After injection of Na125I there was no difference between the kidneys and the liver. In kidney homogenates, radioactivity was present both in the 100,000xg pellet and in the supernatant. The possibility of accumulation or production of the endogenous digitalis-like factor in the kidneys is discussed.

In albino rats, as in other mammals, nucleoli with nucleolonemata and compact nucleoli in the stem cells of the erythrocyte and granulocyte series are progressively replaced during maturation and differentiation first by ring shaped nucleoli and then by micronucleoli with low and finally with inhibited RNA synthesis. There are, however, differences between the nucleolar coefficient values and the proportion of ring shaped nucleoli and micronucleoli in maturing neutrophils in the albino rat, the mouse and man. In the case of the erythroblasts, the differences between the proportion of various nucleolar types in the three given species are smaller. The results thus indicate that the developmental trend of nucleolar changes related to cell maturation and differentiation is the same, but that there are interspecies differences because of which the results obtained in one species cannot be applied mechanically to another, i.e. results obtained in a laboratory animal cannot be applied automatically to man.