a1_In the present paper we describe five tests, 3 of which were designed to be similar to tasks used with rodents. Results obtained from control subjects, patients with selective thermo-coagulation lesions to the medial temporal lobe and results from non-human primates and rodents are discussed. The tests involve memory for spatial locations acquired by moving around in a room, memory for objects subjects interacted with, or memory for objects and their locations. Two of the spatial memory tasks were designed specifically as analogs of the Morris water task and the 8-arm radial-maze tasks used with rats. The Morris water task was modeled by hiding a sensor under the carpet of a room (Invisible Sensor Task). Subjects had to learn its location by using an array of visual cues available in the room. A path integration task was developed in order to study the non-visual acquisition of a cognitive representation of the spatial location of objects. In the non-visual spatial memory task, we blindfolded subjects and led them to a room where they had to find 3 objects and remember their locations. We designed an object location task by placing 4 objects in a room that subjects observed for later recall of their locations. A recognition task, and a novelty detection task were given subsequent to the recall task. An 8-arm radial-maze was recreated by placing stands at equal distance from each other around the room, and asking subjects to visit each stand once, from a central point. A non-spatial working memory task was designed to be the non-spatial equivalent of the radial maze. Search paths recorded on the first trial of the Invisible Sensor Task, when subjects search for the target by trial and error are reported., a2_An analysis of the search paths revealed that patients with lesions to the right or left hippocampus or parahippocampal cortex employed the same type of search strategies as normal controls did, showing similarities and differences to the search behavior recorded in rats. Interestingly, patients with lesions that included the right parahippocampal cortex were impaired relative to patients with lesions to the right hippocampus that spared the parahippocampal cortex, when recall of the sensor was tested after a 30 min delay (Bohbot et al. 1998). No differences were obtained between control subjects and patients with selective thermal lesions to the medial temporal lobe, when tested on the radial-maze, the non-spatial analogue to the radial-maze and the path integration tasks. Differences in methodological procedures, learning strategies and lesion location could account for some of the discrepant results between humans and non-human species. Patients with lesions to the right hippocampus, irrespective of whether the right parahippocampal cortex was spared or damaged, had difficulties remembering the particular configuration and identity of objects in the novelty detection of the object location task. This supports the role of the human right hippocampus for spatial memory, in this case, involving memory for the location of elements in the room; learning known to require the hippocampus in the rat., V.D. Bohbot, R. Jech, E. Růžička, L. Nadel, M. Kalina, K. Štěpánková , J. Bureš., and Obsahuje bibliografii
In order to re-evaluate the presence and relative quantity of 2b and 2x/d myosin heavy chain (MyHC) transcripts in rat slow soleus muscle by using real time RT-PCR we have compared the available relevant cDNA sequences and designed a new set of primers having similar melting temperatures, matching separate MyHC exons in the regions of maximal differences in MyHC coding sequences, and containing G or C at the 3́-end. These also yielded PCR products of corresponding length, which is an important requirement for real time RT-PCR quantification. The experiments were performed on 8- month-old inbred female Lewis strain rats used in our current study of regenerating transplanted muscles. The real time RT-PCR measurement confirmed the expression of all four MyHC mRNAs (type 1, 2a, 2x/d and 2b) in both fast extensor digitorum longus and slow soleus muscles, although in the soleus muscle of adult rats, only type 1 and 2a protein isoforms can be usually detected, J. Žurmanová, F. Půta, R. Stopková, T. Soukup., and Obsahuje bibliografii a bibliografické odkazy
Whole cell patch-clamp recordings from GABAergic cells of thalamic reticular nucleus (RTN) in thalamocortical slices made from postnatal day 6 (P6) to 10 (P10) were used to investigate the pattern of rebound bursts (RBs) triggered by an injection of hyperpolarizing current into RTN cells. The number of RBs in the RTN and the overlying Na+/K+ spikes changed in an agedependent manner. The generation of RBs depended largely on the amplitude of the after-hyperpolarizations (AHPs). RB patterns in response to hyperpolarizing current injection into relay cells were markedly different from RB patterns in RTN cells with an after-depolarization. GABAA receptor antagonist bicuculline methiodide (BMI) changed burst firing patterns, increasing the duration of RB and decreasing the amplitude of AHP in RTN cells. Furthermore, local puffs of NMDA in the presence of BMI induced RBs. K+ channel blocker 4-aminopyridine partially mimicked the effect of BMI on AHPs. The shapes of RBs were altered by a selective CaMKII inhibitor KN-62, but not by an inactive analog KN-04., X. Wang ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The spontaneously hypertensive rat (SHR) is the most widely used animal model of essential hypertension an d accompanying metabolic disturbances. Recent advances in sequencing of genomes of BN- Lx and SHR progenitors of the BXH/HXB recombinant inbred (RI) strains as well as ac cumulation of multiple data sets of intermediary phenotypes in the RI strains, including mRNA and microRNA abundance, quantitative metabolomics, proteomics, methylomics or histone modifications, will make it possible to systematically search for genetic variants involved in regulation of gene ex pression and in the etiology of complex pathophysiological traits. New advances in manipulation of the rat genome, including e fficient transgenesis and gene targeting, will enable in vivo functional analys es of selected candidate genes to identify QTL at the molecular level or to provide insight into mechanisms whereby targeted genes affect pathophysiological traits in the SHR., M. Pravenec ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Sepsis is a life threatening condition that arises when the body's response to an infection injures its own tissues and organs. Sepsis can lead to shock, multiple organ failure and death especially if not recognized early and treated promptly. Molecular mechanisms underlying the systemic inflammatory response syndrome associated with sepsis are still not completely defined and most therapies developed to target the acute inflammatory component of the disease are insufficient. In this s tudy we investigated a possibility of combating sepsis in a mouse model by intravenous treatment with recombinant human tissue non - specific alkaline phosphatase (rhTNAP) derived from transgenic rabbit milk. We induced sepsis in mice by intraperitoneal inje ction of LPS and three hours later treated experimental group of mice by intravenous injection with rhTNAP derived from transgenic rabbits. Such treatment was proved to be physiologically effective in this model, as administration of recombinant rhTNAP suc cessfully combated the decrease in body temperature and resulted in increased survival of mice (80 % vs. 30 % in a control group). In a control experiment, also the administration of bovine intestinal alkaline phosphatase by intravenous injection proved to be effective in increasing survival of mice treated with LPS. Altogether, present work demonstrates the redeeming effect of the recombinant tissue non -specific AP derived from milk of genetically modified rabbits in combating sepsis induced by LPS., B. Bender, M. Baranyi, A. Kerekes, L. Bodrogi, R. Brands, P. Uhrin, Z. Bösze., and Obsahuje bibliografii
The effect of antigenic bacterial lysate IRS-19 on the recovery of blood cells was studied in mice injured by a single dose of 7 Gy irradiation. The preirradiation administration of IRS-19 accelerated the recovery of leukocytes, reticulocytes and platelets in peripheral blood. The recovery of leukocytes 9-14 days after irradiation in protected animals was accompanied by a higher level of band forms of granulocytes as well as activated lymphoid and monocytoid cells., N.O. Macková, P. Fedoročko., and Obsahuje bibliografii
Red palm oil (RPO) is a rich natural source of antioxidant vitamins, namely carotenes, tocopherols and tocotrienols. However, it contains approximately 50 % saturated fatty acids the regular consumption of which could negatively modify lipid profile. The aim of our study was to test whether 7 weeks of RPO supplementation (1 g/kg body weight/day) would affect blood glucose and lipid metabolism in adult male Wistar rats with altered thyroid status. We induced hypothyroidism and hyperthyroidism in rats by oral administration of either methimazole or mixture of thyroid hormones. Different thyroid status (EU - euthyroid, HY - hypothyroid and HT - hyperthyroid) was characterized by different serum thyroid hormones levels (total and free thyroxine and triiodothyronine), changes in the activity of a marker enzyme of thyroid status - liver mitochondrial glycerol-3-phosphate dehydrogenase, and altered absolute and relative heart weights. Fasting blood glucose levels were higher in HT rats in comparison with EU and HY rats, but the changes caused by RPO supplementation were not significant. The achievement of the HY status significantly increased serum levels of total cholesterol, as well as with high-density lipoproteincholesterol and low-density lipoprotein-cholesterol: 2.43±0.15, 1.48±0.09, 0.89±0.08 mmol/l, compared to EU: 1.14±0.06, 0.77±0.06, 0.34±0.05 mmol/l and HT: 1.01±0.06, 0.69±0.04, 0.20±0.03 mmol/l, respectively. RPO supplementation did not increase significantly levels of blood lipids but tended to increase glutathione levels in the liver. In conclusion, RPO supplementation did not induce the presumed deterioration of glucose and lipid metabolism in rats with three well-characterized alterations in thyroid status., H. Rauchová, M. Vokurková, S. Pavelka, I. Vaněčková, N. Tribulová, T. Soukup., and Seznam literatury
Increased amount of collagen type I and decreased amount of type III is described in various pathological processes in the vascular wall. Polyphenols were shown to have protective effect on endothelium, decrease blood pressure and prevent oxidative damage induced by various stimuli. Tetrachlormethane (CCl4) is a toxic substance with known negative systemic effects induced by free radicals. Chronic administration of CCl4 for 12 weeks led to an increase of collagen type I and a decrease of type III in the wall of aorta. Parallel administration of red wine polyphenols significantly reduced the increase of collagen type I, at the same time the content of type III rose to the level above controls. After 4 weeks of spontaneous recovery no changes were observed. If polyphenols were administered during the recovery period, there was a decrease of type I and an increase of type III collagen content in the aorta. It can be concluded that polyphenols have a tendency to lower the amount of type I and to increase the proportion of type III collagen in the wall of the aorta. These changes are significant in prevention or in regression of changes induced by chronic oxidative stress. This effect of polyphenols is most likely the result of their influence on MMP-1 and TIMP activities through which they positively influence the collagen types I and III content ratio in the vascular wall in favor of the type III collagen., L. Hlavačková ... [et al.]., and Obsahuje seznam literatury
The aim of the present study was to investigate the mechanism of vasorelaxant responses induced by red wine polyphenolic compounds (Provinol). Rings of rat femoral artery with or without functional endothelium were set up in a myograph for isometric recording and precontracted with phenylephrine (10-5 M). Provinol in cumulative doses (10-9 to 10-3 mg/ml) elicited endothelium- and dose-dependent relaxation of the artery with maximal relaxation of 56 % at the concentration of 10-5 mg/ml. The relaxant responses to Provinol correlated well with the increase of NO synthase activity in the vascular tissue after administration of cumulative doses of Provinol (10-9 to 10-3 mg/ml). NG-nitro-L-arginine methylester (L-NAME, 3x10-4 M) significantly attenuated the endothelium-dependent relaxation produced by Provinol. Administration of L-arginine (3x10-5 M) restored the relaxation inhibited by L-NAME. The relaxant responses of Provinol were abolished in the presence of Ca2+-entry blocker, verapamil (10-6 M). Administration of hydrogen peroxide (H2O2) abolished acetylcholine (10-5 M)-induced relaxation of the rat femoral artery, while administration of Provinol (10-5 mg/ml) together with H2O2 helped to maintain the acetylcholine-induced relaxation. Provinol only partially affected the concentration-response curve for the NO donor sodium nitroprusside-induced relaxation in rings without endothelium. In conclusion, Provinol elicited endothelium-dependent relaxation of rat femoral artery by the Ca2+-induced increase of NO synthase activity and by protecting NO from degradation., W. Zenebe, O. Pecháňová, R. Andriantsitohaina., and Obsahuje bibliografii