An attempt has been made to test for a reliable method of characterizing the isovolumic left ventricular pressure fall in isolated ejecting hearts by one or two time constants, tau. Alternative nonlinear regression models (three- and four-parametric exponential, logistic, and power function), based upon the common differential law dp(t)/dt = - [p(t)-Ptau]/ tau(t) are compared in isolated ejecting rat, guinea pig, and ferret hearts. Intraventricular pressure fall data are taken from an isovolumic standard interval and from a subinterval of the latter, determined data-dependently by a statistical procedure. Extending the three-parametric exponential fitting function to four-parametric models reduces regression errors by about 20-30 %. No remarkable advantage of a particular four-parametric model over the other was revealed. Enhanced relaxation, induced by isoprenaline, is more sensitively indicated by the asymptotic logistic time constant than by the usual exponential. If early and late parts of the isovolumic pressure fall are discarded by selecting a subinterval of the isovolumic phase, ? remains fairly constant in that central pressure fall region. Physiological considerations point to the logistic model as an advantageous method to cover lusitropic changes by an early and a late tau. Alternatively, identifying a central isovolumic relaxation interval facilitates the calculation of a single ("central") tau; there is no statistical justification in this case to extend the three-parametric exponential further to reduce regression errors., S. F. J. Langer,., and Obsahuje bibliografii
The nucleus accumbens (NAc) core is critical in the control of motivated behaviors. The muscarinic acetylcholine receptors (mAChRs) modulating the excitatory inputs into the NAc core have been reported to impact such behaviors. Recent studies suggest that ventral and dorsal regions of the NAc core seem to be innervated by distinct popula tions of glutamatergic projection neurons. To further examine mAChRs modulation of these glutamatergic inputs to the NAc core, we employed intracellular recordings in rat NAc coronal slice preparation to characterize: 1) the effects of muscarine, an mAChRs agonist, on membrane properties of the NAc core neurons; 2) depolarizing synaptic potentials (DPSP) elicited by ventral and dorsal focal electrical stimuli; and 3) paired-pulse response with paired-pulse stimulation. Here we report that the paired-pulse ratio (PPR) elicited by dorsal stimuli was grea ter than that elicited by ventral stimuli. Bath application of muscarine (1-30 μ M) decreased both ventral and dorsal DPSP in a concentration-dependent manner, with no effect on electrophysiological properties of NAc core neurons. Muscarine at 30 μ M also elicited larger depression of dorsal DPSP than ventral DPSP. Moreover, muscarine increased the PPR of both dorsal and ventral DPSP. These data indicate that the glutamatergic afferent fibers traversing the dorsal and ventral NAc are separate, and that differential decrease of distinct afferent excitatory neurotransmission onto NAc core neurons may be mediated by presynaptic mechanisms., X. Jiang ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Oxidative stress and apoptosis are proposed mechanisms of cellular injury in studies of xenobiotic hepatotoxicity. This study is focused on addressing the mutual relationship and early signals of these mechanisms in the D-galactosamine and lipopolysaccharide (D-GalN/LPS) hepatotoxicity model, with the help of standard liver function and biochemistry tests, histology, and measurement of gene expression by RT-PCR. Intraperitoneal injection of 400 mg/kg D-GalN and 50 μg/kg LPS was able to induce hepatotoxicity in rats, as evidenced by significant increases in liver enzymes (ALT, AST) and raised bilirubin levels in plasma. Heme oxygenase-1 and nitric oxide synthase-2 gene expressions were significantly increa sed, along with levels of their products, bilirubin and nitrite. Th e gene expression of glutathione peroxidase 1 remained unchanged, whereas a decrease in superoxide dismutase 1 gene expression was noted. Furthermore, the significant increase in the gene expression of apoptotic genes Bid, Bax and caspase-3 indicate early activation of apoptotic pathways, which was confirmed by histological evaluation. In contrast, the measured caspase-3 activity remained unchanged. Overall, the results have revealed differential oxidative stress and apoptotic responses, which deserves further investigations in this hepatotoxicity model., N. Lekić ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The glycophenotyping of mammalian cells with plant lectins maps aspects of the glycomic profile and disease-associated alterations. A salient step toward delineating their functional dimension is the detection of endogenous lectins. They can translate sugar-encoded changes into cellular responses. Among them, the members of the lectin family of galectins are emerging regulators of cell adhesion, migration and proliferation. Focusing on galectins-1, -3 and -7, we addressed the issue whether their expression is regulated during wound healing in porcine skin as model. A conspicuous upregulation is detected for galectin-1 in the dermis and a neoexpression in the epidermis, where an increased level of galectin-7 was also found. Applying biotinylated tissue lectins as probes, the signal intensities for accessible binding sites decreased, intimating an interaction of the cell lectin with reactive sites. In contrast, galectin-3 parameters remained rather constant. Of note, epidermal cells in culture also showed an increase in expression/presence of galectin-1, measured on the levels of mRNA and protein, in this case by Western blotting and quantitative immunocytochemistry. Used as matrix, galectin-1 conferred resistance to trypsin treatment to attached human keratinocytes and reduced migration into scratch-wound areas in vitro. This report thus presents new information on endogenous lectins in wound healing and differential regulation among the three tested cases., J. Klíma ... [et al.]., and Obsahuje seznam literatury
We have investigated the role of m- and k-opioid receptors in the central control of preovulatory LH and FSH release in the proestrous rat. Animals were anesthetized with chloral hydrate at 14:00 h on proestrus day. Following femoral artery cannulation, they were mounted in a stereotaxic apparatus. Morphine and U-50488H (benzene-acetamide methane sulphonate) were infused intracerebroventricularly either alone or in combination with naloxone and MR1452, respectively. Controls received sterile saline alone. Blood samples were obtained at hourly intervals between 15:00 h and 17:00 h. Plasma LH and FSH levels were measured by radioimmunoassay. Morphine did not significantly change plasma LH levels at 15:00 h and 16:00 h sampling intervals. A significant increase was observed at 17:00 h compared to the controls (p<0.05). U-50488H significantly increased LH levels at 16:00 h and 17:00 h (p<0.05). The co-administration of naloxone and MR1452 with m- and k-agonist had no significant effect on LH levels at any sampling interval. In all groups, LH levels showed a linear rise over the sampling period between 15:00 h and 17:00 h. None of the treatments significantly altered plasma FSH levels which however, declined towards the end of the afternoon surge. In conclusion, we suggest that the secretion of LH and FSH is differentially regulated by m- and k-opioid receptors. It is thought that in all groups chloral hydrate interfered with the LH surge secretory systems., S. Kumru, M. Şimşek, B. Yilmaz, E. Sapmaz, S. Kutlu, S. Sandal, S. Canpolat., and Obsahuje bibliografii
In our study, the circadian blood pressure (BP) rhythm was studied in subjects with asymptomatic and normotensive pheochromocytoma. We have therefore performed 24-hour BP monitoring not only in 6 subjects with asymptomatic pheochromocytoma, but also in 33 patients with symptomatic pheochromocytoma and in 10 normotensive subjects, who served as a control group. Circadian BP rhythm was expressed by assessing a relative night-time BP decline. We found a similar BP rhythm, catecholamine excretion and tumor size in subjects with both forms of pheochromocytoma. Subjects with asymptomatic pheochromocytoma had a significantly lower night-time systolic BP decline (P=0.01) and diastolic BP decline (P=0.006) than normotensive controls. We conclude that the attenuated night-time BP decline in normotensive and asymptomatic subjects with pheochromocytoma might be a possible sign of partial desensitization of the cardiovascular system to catecholamines., T. Zelinka, J. Widimský, J. Weisserová., and Obsahuje bibliografii
The activity of 194 neurons was recorded in three subdivisions of the medial geniculate body (74 neurons in the ventral, 62 in the medial and 44 neurons in the dorsal subdivision, i.e. vMGB, mMGB and dMGB) of guinea pigs anesthetized with ketamine-xylazine. The discharge properties of neurons were evaluated by means of peristimulus time histograms (PSTHs), interval histograms (INTHs) and auto-correlograms (ACGs). In the whole MGB, the most frequent PSTH responses to pure tone stimuli were onset (43 %) or chopper (32 %). The onset responses were mostly present in the vMGB, whereas chopper responses dominated in the dMGB. In the whole MGB Poisson-like and bimodal INTHs were found in 46 % and 40 % of neurons, respectively. The mMGB revealed fewer bimodal and more symmetrical types of INTH. In the whole MGB, 60 % of units were found to have ACGs typical for short bursts (<100 ms), 23 % for long bursts (>100 ms) and 15 % of units fired without bursts. Neurons in the vMGB were characterized by short bursting, whereas those in the mMGB and dMGB expressed more activity in the long bursts. The results demonstrate that the type of information processing in the vMGB, which belongs to the ”primary” auditory system, is different from that in two other subdivisions of the MGB., E. Kvašňák, J. Popelář, J. Syka., and Obsahuje bibliografii
Mechanism responsible for the en largement of end-expiratory lung volume (EELV) induced by chronic hypoxia remains unclear. The fact that the increase in EELV persists after return to normoxia suggests involvement of morphological changes. Because hypoxia has been also show n to activate lung mast cells, we speculated that th ey could play in the mechanism increasing EELV similar role as in vessel remodeling in hypoxic pulmonary hypertension (HPH). We, therefore, tested an effect of mast cells degranulation blocker disodium cromoglycate (DSCG) on hypoxia induced EELV enlargement. Vent ilatory parameters, EELV and right to left heart weight ratio (RV/LV+S) were measured in male Wistar rats. The experimental group (H+DSCG) was exposed to 3 weeks of normobaric hypoxia and treated with DSCG during the first four days of hypoxia, control group was exposed to hypoxia only (H), two others were kept in normoxia as non-treated (N) and treated (N+DSCG) groups. DSCG treatment significantly attenuated the EELV enlargement (H+DSCG=6.1 ± 0.8; H=9.2 ± 0.9; ml ± SE) together with the increase in minute ventilation (H+DSCG=190 ± 8; H=273 ± 10; ml/min ± SE) and RV/LV+S (H+DSCG=0.39 ± 0.03; H=0.50 ± 0.06)., H. Maxová, A. Hezinová, M. Vízek., and Obsahuje bibliografii a bibliografické odkazy
a1_We hypothesize that hypokalemia-related electrolyte imbalance linked with abnormal elevation of intracellular free Ca2+ concentration can cause metabolic disturbances and subcellular alterations resulting in intercellular uncoupling, which favor the occurrence of malignant arrhythmias. Langendorff-perfused guinea pig heart (n = 44) was subjected to a standard Tyrode solution (2.8 mmol/l K+) followed by a K+-deficient solution (1.4 mmol/l K+). Bipolar ECG of the left atria and ventricle was continuously monitored and the incidence of ventricular fibrillation was evaluated. Myocardial tissue sampling was performed during stabilization, hypokalemia and at the onset of fibrillation. Enzyme activities of succinic dehydrogenase, glycogen phosphorylase and 5-nucleotidase were determined using in situ catalytic histochemistry. The main gap junction protein, connexin-43, was labeled using mouse monoclonal antibody and FITC conjugated goat antimouse antibody. Ultrastructure was examined by transmission electron microscopy. The free Ca2+ concentration was measured by the indo-1 method in ventricular cell cultures exposed to a K+-free medium. The results showed that sustained ventricular fibrillation appeared within 15-30 min of low K+ perfusion. This was preceded by ectopic activity, episodes of bigeminy and tachycardia. Hypokalemia induced moderate reversible and sporadically irreversible subcellular alterations of cardiomyocytes and impairment of intercellular junctions, which were heterogeneously distributed throughout myocardium. Patchy areas with decreased enzyme activities and diminished immunoreactivity of connexin-43 were found. Furthermore, lack of external K+ was accompanied by an increase of intracellular Ca2+. The prevention of Ca2+ overload by either 1 mmol/l Ni2+ (Na+/Ca2+ inhibitor), 2.5 mmol/l verapamil, 10 mmol/l d-sotalol or 10 mmol/l tedisamil was associated with the protection agains fibrillation., a2_The results indicate that hypokalemia induces Ca2+ overload injury and disturbances in intercellular coupling. Dispersion of these changes throughout the myocardium may serve as the basis for microreentry circuits and thus favor fibrillation occurrence., N. Tribulová, M. Manoach, D. Varon, L. Okruhlicová, T. Zinman , A. Shainberg., and Obsahuje bibliografii
Multiple lines of evidence suggest the participation of the hippocampus in the feedback inhibition of the hypothalamus- pituitary-adrenal axis during stress response. This inhibition is mediated by glucocorticoid feedback due to the sensitivity of the hippocampus to these hormones. The sensitivity is determined by the expression of glucocorticoid (GR) and mineralocorticoid (MR) receptors and 11 β -hydroxysteroid dehydrogenase type 1 (11HSD1), an enzyme that re gulates the conversion of glucocorticoids from inactive to active form. The goal of our study was to assess the effect of stress on the expression of 11HSD1, GR and MR in the ventral and dorsal region of the CA1 hippocampus in three different rat strains with diverse responses to stress: Fisher 344, Lewis and Wistar. Stress stimulated 11HSD1 in the ventral but not dorsal CA1 hippocampus of Fisher 344 but not Lewis or Wistar rats. In contrast, GR expression following stress was decreased in the dorsal but not ventral CA1 hippocampus of all three strains. MR expression was not changed in either the dorsal or ventral CA1 region. These results indicate that (1) depending on the strain, stress stimulates 11HSD1 in the ventral hippocampus, which is known to be involved in stress and emotion reactions whereas (2) independent of strain, stress inhibits GR in the dorsal hippocampus, which is predominantly involved in cognitive functions., P. Ergang ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy