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
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
Prolonged exposure to alveolar hypoxia induces physiological changes in the pulmonary vasculature that result in the development of pulmonary hypertension. A hallmark of hypoxic pulmonary hypertension is an increase in vasomotor tone. In vivo, pulmonary arterial smooth muscle cell contraction is influenced by vasoconstrictor and vasodilator factors secreted from the endothelium, lung parenchyma and in the circulation. During chronic hypoxia, production of vasoconstrictors such as endothelin-1and angiotensin II is enhanced locally in the lung, while synthesis of vasodilators may be reduced. Altered reactivity to these vasoactive agonists is another physiological consequence of chronic exposure to hypoxia. Enhanced contraction in response to endothelin-1 and angiotensin II, as well as depressed vasodilation in response to endothelium-derived vasodilators, has been documented in models of hypoxic pulmonary hypertension. Chronic hypoxia may also have direct effects on pulmonary vascular smooth muscle cells, modulating receptor population, ion channel activity or signal transduction pathways. Following prolonged hypoxic exposure, pulmonary vascular smooth muscle exhibits alterations in K+ current, membrane depolarization, elevation in resting cytosolic calcium and changes in signal transduction pathways. These changes in the electrophysiological parameters of pulmonary vascular smooth muscle cells are likely associated with an increase in basal tone. Thus, hypoxia-induced modifications in pulmonary arterial myocyte function, changes in synthesis of vasoactive factors and altered vasoresponsiveness to these agents may shift the environment in the lung to one of contraction instead of relaxation, resulting in increased pulmonary vascular resistance and elevated pulmonary arterial pressure., L. A. Shimoda, J. S. K. Sham, J. T. Sylvester., and Obsahuje bibliografii
Metabotropic glutamate receptors (mGluRs) represent a potential therapeutic target. Possible anticonvulsant action of AMN 082, an agonist of mGluR7 subtype, was studied in immature rats using pentylenetetrazol (PTZ)-induced seizures as a model. Five age groups of rats (7-, 12-, 18-, 25-day-old and adult animals) were pretreated with AMN 082 in doses of 0.5, 1, 2, and 5 mg/kg i.p. and 30 min later PTZ was administered (100 mg/kg s.c.). Controls received saline instead of the agonist. AMN 082 did not exhibit clear anticonvulsant action with the exception of suppression of the tonic phase of generalized tonic-clonic seizures (GTCS) in 12-day-old rats. Shorter latencies of GTCS after AMN 082 pretreatment indicate a proconvulsant action. Involuntary movements (mostly tremor) appeared after AMN 082 before PTZ administration, therefore we performed another experimental series with AMN 082 only (1, 2, 5, and 10 mg/kg i.p.). During 60-min observation period tremor appeared in all age groups; sensitivity to this action decreased with age from the 2 mg/kg dose in 7- and 12-day-old rats to the 10 mg/kg dose in adult rats. Mixed anti- and proconvulsant actions of AMN 082 together with unwanted motor effects makes clinical use of this drug highly improbable., Pavel Mareš., and Obsahuje bibliografii a bibliografické odkazy
5-hydroxytryptamine (5-HT) is involved in the stress-induced alteration of colonic functions, specifically motility and secretion, but its precise mechanisms of regulation remain unclear. In the present study, we have investigated the effects of 5-HT on rat colonic mucosal secretion after acute water immersion restraint stress, as well as the underlying mechanism of this phenomenon, using short circuit current recording (ISC), real-time polymerase chain reaction, Western blot analysis, and enzyme-linked immunosorbance assays. After 2 h of water immersion restraint stress, the baseline ISC and 5-HT-induced ISC responses of the colonic mucosa were significantly increased. Pretreatment with selective 5-HT4 receptor antagonist, SB204070, inhibited the 5-HT-induced colonic ISC response by 96 % in normal rats and 91.2 % in acute-stress rats. However, pretreatment with the selective antagonist of 5-HT3 receptor, MDL72222 or Y-25130, had no obvious effect on 5-HT-induced ISC responses under either set of conditions. Total protein expression of both the mucosal 5-HT3 receptors and the 5-HT4 receptors underwent no significant changes following acute stress. Both colonic basal cAMP levels and foskolin-induced ISC responses were significantly enhanced in acute stress rats. 5-HT significantly enhanced the intracellular cAMP level via 5-HT4 receptors in the colonic mucosa from both control and stressed animals, and 5-HT-induced cAMP increase in stressed rats was not more than that in control rats. Taken together, the present results indicate that acute water immersion restraint stress enhances colonic secretory responses to 5-HT in rats, a process in which increased cellular cAMP accumulation is involved., Y. Li, L. S. Li, X. L. Zhang, Y. Zhang, J. D. Xu, J. X. Zhu., and Obsahuje bibliografii
Peritoneal dialysis (PD) is a well established method of depuration in uremic patients. Standard dialysis solutions currently in use are not biocompatible with the peritoneal membrane. Studying effects of dialysate on peritoneal membrane in humans is still a challenge. There is no consensus on the ideal experimental model so far. We, therefore, wanted to develop a new experimental non-uremic rabbit model of peritoneal dialysis, which would be practical, easy to conduct, not too costly, and convenient to investigate the long-term effect of dialysis fluids. The study was done on 17 healthy Chinchilla male and female rabbits, anesthetized with Thiopental in a dose of 0.5 mg/kg body mass. A catheter, specially made from Tro-soluset (Troge Medical GMBH, Hamburg, Germany) infusion system, was then surgically inserted and tunneled from animals' abdomen to their neck. The planned experimental procedure was 4 weeks of peritoneal dialysate instillation. The presented non-uremic rabbit model of peritoneal dialysis is relatively inexpensive, does not require sophisticated technology and was well tolerated by the animals. Complications such as peritonitis, dialysis fluid leakage, constipation and catheter obstruction were negligible. This model is reproducible and can be used to analyze the effects of different dialysis solutions on the rabbit peritoneal membrane., S. Zunic-Bozinovski, Z. Lausevic, S. Krstic, N. Jovanovic, J. Trbojevic-Stankovic, B. Stojimirovic., and Obsahuje bibliografii a bibliografické odkazy