The aim of our study was to test the hypothesis, whether repeated allopurinol pre-treatment (in dose of 135 mg/kg s.c.) can influence changes of brain excitability caused by long-term hypoxia exposition in young immature rats. Rat pups were exposed together with their mother in to an intermittent hypobaric hypoxia (simulated altitude of 7 000 m) since the day of birth till the 11th day (youngest experimental group) or 17th day for 8 hours a day. Allopurinol was administered daily immediately before each hypoxia exposition. The duration of evoked afterdischarges (ADs) and the shape of evoked graphoelements were evaluated in 12, 18, 25 and 35-day-old freely moving male pups. Hypobaric hypoxia prolonged the duration of ADs in 12, 18 and 25-day-old rats. The ADs were prolonged in 35-day-old rats only after the first stimulation. Allopurinol shorted the duration of ADs only in 12-day-old pups. In older experimental group the effect of allopurinol treatment was less pronounced., K. Jandová, ... [et al.]., and Obsahuje seznam literatury
Action of carbamazepine (50 mg/kg i.p.) and phenytoin (60 mg/kg i.p.) on the activity of cerebellar neurones was studied in rats under urethane anaesthesia. Carbamazepine markedly decreased the firing frequency of all ten neurones recorded continually before and after drug administration. The same conclusion was reached when a group of 53 cells recorded before drug administration was compared with 48 neurones recorded after carbamazepine administration only. The effects of phenytoin were ambiguous - a decrease as well as an increase in frequency was recorded. The solvent used did not change cerebellar unit activity. Cerebellum cannot be considered as a possible target structure for phenytoin but it might be a target for carbamazepine action.
Epileptic afterdischarges elicited by electrical stimulation of the dorsal hippocampus in freely moving rats were not significantly changed by flunarizine administration in comparison with control sessions in which the animals received the solvent only. On the other hand, flunarizine significantly reduced the number of wet dog shakes, the main automatisms accompanying limbic afterdischarges.
A low birth weight is a new risk factor for the development of premature atherosclerosis. The effect of intrauterine undernutrition on hypercholesterolemia in later life was studied in an experimental model using the Prague Hereditary Hypercholesterolemic (PHHC) rat. Compared to animals in the control group (Wistar rats), animals with an increased sensitivity to high-cholesterol diet (PHHC rats) display hypercholesterolemia. Only in PHHC animals, individuals undernourished in their intrauterine life (hypotrophic group, HG) had a significantly higher total cholesterol, compared with individuals without food restriction in pregnancy (eutrophic group, EG). Restricted food intake in pregnancy led to smaller nests and a decreased number of pups in each litter. We found no significant diferences in birth weight between HG and EG. In spite of similar birth weights in PHHC and Wistar rats, intrauterine undernutrition caused an increase in cholesterolemia in the HG group of the PHHC rats. The effect of intrauterine undernutrition on the development of hypercholesterolemia will most likely play a role in individuals with geneticaly determined increased susceptibility to a high-cholesterol diet. The use of this model of intrauterine undernutrition for the study of hypercholesterolemia has proved to be feasible., P. Szitányi, J. Hanzlová, R. Poledne., and Obsahuje bibliografii
Consumption of seafood containing toxin domoic acid (DA) causes an alteration of glutamatergic signaling pathways and could lead to various signs of neurotoxicity in animals and humans. Neonatal treatment with domoic acid was suggested as valuable model of schizophrenia and epilepsy. We tested how repeated early postnatal DA administration influences the spontaneous behavior of rats in adulthood. Rats were injected with 30 μg DA/kg from postnatal day (PND) 10 until PND 14. Their behavior was observed in the open field test for one hour (Laboras, Metris) at PND 35, PND 42 and PND 112. We did not find any difference between DA treated rats and animals injected with equivalent volume of saline in both test sessions at PND 35 and PND 42. DA rats at PND 112 exhibited significantly higher vertical and horizontal exploratory activity (tested parameters: locomotion, distance travelled, average speed reached during test, grooming and rearing) between the 30th-40th min of the test session and habituated over 10 min later. We conclude that at least in the given experimental design, neonatal DA treatment results in alteration of the spontaneous behavior of rats in adulthood., K. Jandová, P. Kozler, M. Langmeier, D. Marešová, J. Pokorný, V. Riljak., and Obsahuje bibliografii
Effect of phénobarbital (PhB, 20 and/or 40 mg/kg) on epileptic ECoG phenomena induced by metrazol was studied in acute experiments in rats aged 7, 12, 18, 25 and 90 days. Fractionated administration of metrazol (20 mg/kg i.p. each 300 s) was used to quantify the effects of PhB. First signs of metrazol action (sharp elements and/or rhythmic metrazol activity) were not reliably influenced by PhB. On the contrary, the latency of the first EEG seizures as well as of the first generalized EEG seizures was prolonged and thus a dose necessary for their elicitation was increased in all age groups. These differences reached statistical significance in 12-, 18- and 25-day-old rats. A lack of effect of PhB against the rhythmic metrazol activity supports the adequacy of this activity as a model of human absences. Differences between the development of antiepileptic and hypnotic effects of PhB (described earlier) suggest two different mechanisms of action.
The action of phenytoin and valproate on thalamocortical responses was studied in adult rats. Single responses were not influenced by either drug. Paired-pulse potentiation of the initial components (first positive and first negative) observed with intervals from 50 to 200 ms under control conditions was abolished by phenytoin (60 mg/kg i.p.) but only moderately influenced by valproate (400 mg/kg i.p.). Paired-pulse potentiation of thalamocortical phenomena cannot be put into connection with the generation of the spike-and-wave rhythm.
The inhibitory effect of 2 % ethanol (400 mM) in the incubation medium on several characteristics of the Na+-ATPase of basolatcral plasma membranes from rat kidney proximal tubular cells was investigated. Ethanol did not change the Km of the enzyme for Mg2+, ATP or Na + ; it did not change either the optimal pH or temperature values of the incubation medium for the enzyme to act and finally, it did not affect the apparent energy of activation of the enzyme. It was also found that 2 % ethanol produced stronger inhibition of the ATPase when it is in an activated or stimulated state, than when it is working at its lower basal level. The presented results can be explained by assuming that 2 % ethanol in the incubation medium inhibits Na +-ATPase activity by affecting the enzyme structure as well as its activating mechanism.
We studied the effects of hydrocortisone as a possible regulatory factor of bone blood flow and metabolism. Local bone blood flow in the tibia, distal femur, lumbar vertebra and some soft tissues (using 85Sr-microspheres), as well as 45Ca and 3H-proline incorporation into the tibia, bone density and ash weight per ml of the tibia were measured in sham-operated and oophorectomized female rats in which the influence of hydrocortisone administration (0.004 % diet for 5 weeks) was followed. Hydrocortisone markedly lowered 85Sr-microsphere uptake and blood flow through the bones of non-castrated female rats as well as elevated circulatory values in oophorectomized rats. The changes were nearly identical in the three bone samples measured; among the soft tissues only the kidneys showed a less pronounced decrease. Circulatory changes in the bones seem to be caused by local vascular reactions. Hydrocortisone also lowered the 24-hour incorporation of 45Ca and 3H-proline into the tibia of both non-castrated and oophorectomized females. In the tibia of oophorectomized rats, hydrocortisone normalized the decreased bone density and ash weight. The adrenocortical hormones are known to block eicosanoid synthesis by the inhibition of arachidonic acid production. It is possible, therefore, that local circulatory changes in the bones of rats, induced by hydrocortisone, are mediated by the changes in prostaglandin production.
In experimental and human diabetes mellitus, evidence for an impaired function of the vascular endothelium has been found and has been suggested to contribute to the development of vascular complications in this disease. The aim of the study was to evaluate possible regional hemodynamic in vivo differences between healthy and diabetic rats which would involve nitric oxide (NO). Central hemodynamics and regional blood flow (RBF) were studied using radioactive microspheres in early streptozotocin (STZ)-diabetic rats and compared to findings in healthy control animals. This method provides a possibility to study the total blood flow and vascular resistance (VR) in several different organs simultaneously. L-NAME iv induced widespread vasoconstriction to a similar extent in both groups. In the masseter muscle of both groups, acetylcholine 2 μg/kg per min, induced a RBF increase, which was abolished by pretreatment with L-NAME, suggesting NO as a mediator of vasodilation. In the heart muscle of both groups, acetylcholine alone was without effect while the combined infusion of acetylcholine and L-arginine induced an L-NAME-sensitive increase in RBF. The vasodilation induced by high-dose acetylcholine (10 μg/kg per min) in the kidney was more pronounced in the STZ-diabetic rats. The results indicate no reduction in basal vasodilating NO-tone in the circulation of early diabetic rats. The sensitivity to vasodilating effects of acetylcholine at the level of small resistance arterioles vary between tissues but was not impaired in the diabetic rats. In the heart muscle the availability of L-arginine was found to limit the vasodilatory effect of acetylcholine in both healthy and diabetic rats. In conclusion, the results indicate a normal action of NO in the investigated tissues of the early STZ-diabetic rat., E. Granstam, S.-O. Granstam., and Obsahuje bibliografii