The consequences of epileptic seizures related to postictal inhibition in early postictal period include postictal analgesia. We studied this phenomenon over 96 h following flurothyl-induced seizures in adult male Wistar rats. Nociception of control (no seizure) and seizured groups were tested using the plantar and von Frey hair tests. We determined latency of forepaw and hind paw reactions using plantar tests and the number of von Frey hairs reactions. Shortly after seizures, longer plantar test latencies were seen relative to the control group. Before the seizures the plantar test reaction times were significantly shorter in forepaws than in hind paws. The effect disappeared post-seizure and surprisingly, it also disappeared at the corresponding time in controls; it reappeared after 48 h in the seizure group and after 24 h in controls. Differences in the von Frey hairs test occurred at 5 and 60 min post-seizure, however, these differences could not be explained by limb anatomy; although, different thermal and mechanical nociception mechanisms could be significant. The unexpected reactions in controls could be related to brief social and physical interactions between the two groups. and J. Mareš, R. Rokyta.
In the present work neonatal male and female Wistar rats were treated intraperitoneally with monosodium glutamate (MSG 2 mg/kg b.w.) or saline (controls) daily for 4 day after birth. At the age of 30 and 80 days, the alkaline phosphatase activity (AP) in the brush border of individual enterocytes, the body fat content and Lee´s index of obesity were analyzed. Microdensitometrical quantification of AP was significantly increased on day 30 in males (P<0.01) and on day 80 in MSG-treated male and female rats (P<0.001) as compared to the controls. MSG administration also increased the body fat weight and the obesity index significantly (P<0.001) in 80-day-old animals, but was without any significant effect on their food intake. Our results showed that a) neonatal MSG-treatment may significantly change the intestinal function and b) the investigation of the intestinal enzyme activities may be important in further studies on MSG-induced and other forms of obesity., Š. Mozeš, Ľ. Lenhardt, A. Martinková., and Obsahuje bibliografii
The polymorphisms of the tumor suppressor gene p53 in exon 4 (p53 BstUI) and in intron 6 (p53 MspI) have been suggested to be associated with the genetically determined susceptibility in diverse types of human cancer. In our hospital-based case-control study, we examined the allele and genotype incidence of these polymorphisms as well as their haplotype combinations in 60 brain tumor patients (27 males and 33 females) and 183 controls without malignancies. The genotype characteristics were determined by the PCR-based RFLP method using DNA extracted from peripheral blood. In this study we show that the p53 BstUI and the p53 MspI polymorphisms are not associated with increased risk of brain tumors. Thus, we conclude that the p53 BstUI and the p53 MspI polymorphic sites within the tumor suppressor gene p53 do not represent genetic determinants of susceptibility to brain tumors., E. Biroš, I. Kalina, A. Kohút, E. Bogyiová, J. Šalagovič, I. Šulla., and Obsahuje bibliografii
The aim of this study was to test the hypothesis that allopurinol ingestion modifies the slow component of • VO2 kinetics and changes plasma oxidative stress markers during severe intensity exercise. Six recreationally active male subjects were randomly assigned to receive a single dose of allopurinol (300 mg) or a placebo in a double-blind, placebo-controlled crossover design, with at least 7 days washout period between the two conditions. Two hours following allopurinol or placebo intake, subjects completed a 6-min bout of cycle exercise with the power output corresponding to 75 % • VO2 max. Blood samples were taken prior to commencing the exercise and then 5 minutes upon completion. Allopurinol intake caused increase in resting xanthine and hypoxanthine plasma concentrations, however it did not affect the slow component of oxygen uptake during exercise. Exercise elevated plasma inosine, hypoxanthine, and xanthine. Moreover, exercise induced a decrease in total antioxidant status, and sulfhydryl groups. However, no interaction treatment x time has been observed. Short term severe intensity exercise induces oxidative stress, but xanthine oxidase inhibition does not modify either the kinetics of oxygen consumption or reactive oxygen species overproduction., R. A. Olek ... [et al.]., and Obsahuje seznam literatury
Ivermectin acts as a positive allosteric regulator of several ligand gated channels including the glutamate-gated chloride channel (GluCl), γ-aminobutyric acid type-A receptor, glycine receptor, neuronal α 7-nicotinic receptor and purinergic P2X4 receptor. In most of the ivermect in-sensitive channe ls, the effects of ivermectin include the potentiation of agonist-induced currents at low concentrations and channel opening at higher concentrations. Based on mutagenesis, electrophysiological recordings and functional an alysis of chimeras between ivermectin-sensitive and ivermectin-insensitive receptors, it has been concluded that ivermectin acts by insertion between transmembrane helices. The three-dimensional structure of C. elegans GluCl complexed with ivermectin has revealed the details of the ivermectin-binding site, however, no generic motif of amino acids could accurately predict ivermectin binding site for other ligand gated channels. Here, we will review what is currently known about ivermectin binding and modulation of Cys-loop receptor family of ligand-gated ion channels and what are the critical structur al determinants underlying potentiation of the P2X4 receptor channel., H. Zemkova ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
STR/N is an inbred strain of mice which is known to exhibit extreme polydipsia and polyuria. We previously found central administration of angiotensin II enhanced cardiovascular responses in STR/N mice than normal mice, suggesting that STR/N mice might exhibit different cardiovascular responses. Therefore, in this study, we investigated daily mean arterial blood pressure and heart rate, and changes in the baroreceptor-heart rate reflex in conscious STR/N mice and control (ICR) mice. We found that variability in daily mean arterial blood pressure and heart rate was significantly larger in STR/N mice than in ICR mice (p<0.05). There was a stronger response to phenylephrine (PE) in STR/N mice than in ICR mice. For baroreceptor reflex sensitivity, in the rapid response period, the slopes of PE and sodium nitroprusside (SNP) were more negative in STR/N mice than in ICR mice. In the later period, the slopes of PE and SNP were negatively correlated between heart rate and blood pressure in ICR mice, but their slopes were positively correlated in STR/N mice. These results indicated that STR/N mice exhibited the different cardiovascular responses than ICR mice, suggesting that the dysfunction of baroreceptor reflex happened in conscious STR/N mice., C. P. Chu, B. R. Cui, H. Kannan, D. L. Qiu., and Obsahuje bibliografii
The oxidative mechanisms of injury-induced damage of neurons within the spinal cord are not very well understood. We used a model of T8-T9 spinal cord injury (SCI) in the rat to induce neuronal degeneration. In this spinal cord injury model, unilateral avulsion of the spinal cord causes oxidative stress of neurons. We tested the hypothesis that apurinic/apyrimidinic endonuclease (or redox effector factor-1, APE/Ref-1) regulates this neuronal oxidation mechanism in the spinal cord region caudal to the lesion, and that DNA damage is an early upstream signal. The embryonic neural stem cell therapy significantly decreased DNA- damage levels in both study groups - acutely (followed up to 7 days after SCI), and chronically (followed up to 28 days after SCI) injured animals. Meanwhile, mRNA levels of APE/Ref-1 significantly increased after embryonic neural stem cell therapy in acutely and chronically injured an imals when compared to acute and chronic sham groups. Our da ta has demonstrated that an increase of APE/Ref-1 mRNA levels in the caudal region of spinal cord strongly correlated with DNA damage after traumatic spinal cord injury. We suggest that DNA damage can be observed both in lesional and caudal regions of the acutely and chronically injured groups, but DNA damage is reduced with embryonic neural stem cell therapy., T. Dagci, G. Armagan, S. Konyalioglu, A. Yalcin., and Obsahuje bibliografii
Both brain and peripheral nitric oxide (NO) play a role in the control of blood pressure and circ ulatory homeostasis. Central NO production seems to counteract angiotensin II-induced enhancement of sympathetic tone. The aim of our study was to evaluate NO synthase (NOS) activity and protein expression of its three isoforms - neuronal (nNOS), endothelial NOS (eNOS) and inducible (iNOS) - in two brain regions involved in blood pressure control (diencephalon and brainstem) as well as in the kidney of young adult rats with either genetic (12-week-old SHR) or salt- induced hypertension (8-week-old Dahl rats). We have demonstrated reduced nNOS and iNOS expression in brainstem of both hypertensive models. In SHR this abnormality was accompanied by attenuated NOS activity and was corrected by chronic captopril treatment which prevented the development of genetic hypertension. In salt hypertensive Dahl rats nNOS and iNOS expression was also decrea sed in the diencephalon where neural structures important for salt hypertension development are located. As far as peripheral NOS activity and expression is concerned, renal eNOS expression was considerably reduced in both genetic and salt-induced hypertension. In conclusions, we disclosed similar changes of NO system in the brainstem (but not in the diencephalon) of rats with genetic and salt-induced hypertension. Decreased nNOS ex pression was associated with increased blood pressure due to enhanced sympathetic tone., S. Hojná, J. Kuneš, J. Zicha., and Obsahuje bibliografii
The aim was to study the blood-brain permeability according to the distribution in the rat brain of Evans blue (EB) and sodium fluorescein (NaFl) administered by an intracarotid injection. Eighteen animals were divided into six groups according to the state of the blood-brain barrier (BBB) at the moment when the dyes were being applied. In the first two groups, the BBB was intact, in groups 3 and 4 the barrier had been opened osmotically prior to the application of the dyes, and in groups 5 and 6 a cellular edema was induced by hyperhydration before administration of the dyes. The intracellular and extracellular distribution of the dyes was studied by fluorescence microscopy. The histological picture thus represented the morphological correlate of the way BBB permeability had been changed before the application of the dyes., P. Kozler, J. Pokorný., and Obsahuje bibliografii
Cardiac fibrotization is a well-known process characteristic of many cardiac pathological conditions. The key element is excessive activation of cardiac fibroblasts, their transdifferentiation into myofibroblasts, increased production, and accumulation of extracellular matrix proteins, resulting in cardiac stiffness. The exact cellular mechanisms and molecular components involved in the process are not fully elucidated, but the SOCE mechanism could play an important role. Its key molecules are the molecular sensor of calcium in ER/SR - STIM and the highly selective calcium channels Orai located in the plasma membrane. This study aims to evaluate selected SOCEassociated genes in the activation of HCF cell culture by several known substances (phenylephrine, isoprenaline) that represent cardiovascular overload. After cell cultivation, cell medium was collected to measure the soluble collagen content. From the harvested cells, qRT-PCR was performed to determine the mRNA levels of the corresponding genes. The activation of cells was based on changes in the relative expression of collagen genes as well as the collagen content in the medium of the cell culture. We detected an increase in the expression of the Orai2 isoform, a change in the Orai1/Orai3 ratio and also an increase in the expression of the STIM2 isoform. These results suggest an increased activation of the SOCE mechanism under stress conditions of fibroblasts, which supports the hypothesis of fibroblast activation in pathological processes by altering calcium homeostasis through the SOCE mechanism., Róbert Čendula, Nikola Chomaničová, Adriana Adamičková, Andrea Gažová, Ján Kyselovič, Marek Máťuš., and Obsahuje bibliografii