Anticonvulsant action of vigabatrin (300, 600, 900 and/or 1200 mg/kg i.p.), an inhibitor of GABA-transaminase, was studied in a model of motor sezures elicited by pentylenetetrazol. Five age groups of rats (7, 12, 18, 25 and 90 days old) received a s.c. injection of pentylenetetrazol 4, 6 and/or 24 hours after vigabatrin administration. The incidence of minimal, predominantly clonic seizures was not changed in any age group, but their latencies were prolonged in 18- and 25-day-old rats. Generalized tonic-clonic seizures were influenced in a more complex manner. Incidence of these seizures was decreased in 7-day-old rat pups 24 hours after vigabatrin administration. Higher doses of vigabatrin exhibited a similar effect in adult rats at all intervals studied. Specific suppression or at least restriction of the tonic phase was observed in all groups of immature rats, the effect was more marked 24 hours after vigabatrin than at shorter intervals. The anticonvulsant action of vigabatrin, which could be demonstrated mainly against generalized tonic-clonic seizures, varies markedly during development., R. Haugvicová, H. Kubová, P. Mareš., and Obsahuje bibliografii
This study investigated quantitated expression of dopamine 2 receptor (D2R) and somatostatin receptors of the five types (SSTR1-SSTR5) in a large series of clinically non-functioning pituitary adenomas (CNFAs). Co-expression of these receptors in individual adenomas was studied as well as correlation between receptor types. Adenoma tissue from 198 patients who underwent surgery for CNFAs was analyzed by immunohistochemistry and quantitative real-time PCR. D2R and SSTR1-3 mRNA was expressed in all 198 adenomas. SSTR4 and SSTR5 were detectable in 85 % and 61 % of adenomas, respectively. Expression of D2R was significantly higher than that of the somatostatin receptors. The median relative expressions were as follows from highest D2R >> SSTR3 > SSTR2 > SSTR1 > SSTR5 > SSTR4. High relative expression (ratio to β-glucuronidase mRNA > 1) of D2R was found in 60 % of tumors, high expression of SSTR1 in 7.5 %, SSTR2 in 7 %, SSTR3 in 4 % and SSTR5 in 0.5 %. The quantity of D2R correlated positively with expression of SSTR2 and SSTR3, and negatively with SSTR1 and SSTR5. Among histological adenoma types, SSTR1 was significantly higher in null-cell adenomas and SSTR3 was lower in silent corticotroph adenomas. In conclusions, in CNFAs, high expression of somatostatin receptors is much less common than that of D2R, and co-expression of both these receptors is exceptional. D2R and SSTR3 seem to be the most promising targets for pharmacological treatment., F. Gabalec, M. Drastikova, T. Cesak, D. Netuka, V. Masopust, J. Machac, J. marek, J. Cap, M. Beranek., and Obsahuje bibliografii
The aim of this study was to examine the influence of unilateral dorsal root section at the cervicothoracic level of the spinal cord on the spontaneous neuronal activity of medial thalamic nuclei in the rat. Single unit extracellular recordings from thalamic nuclei, nc. parafascicularis and nc. centralis lateralis, were obtained with glass micropipettes. The abnormal bursting activity of these nuclei following deafferentation was registered, although a correlation between the occurrence of this activity and the degree of autotomy behavior was not found. Such bursts were never observed in the studied thalamic nuclei of control rats., Š. Vaculín, M. Franěk, R. Rokyta., and Obsahuje bibliografii
Drug abuse during pregnancy is a growing problem in all developed countries all over the world. The drugs easily cross the placental barrier into the fetal body and are present also in the maternal milk. Therefore, it may affect the development of the child pre- as well as postnatally. The effects of prenatal drug exposure are long-lasting and persist until adulthood. The present review summarizes the clinical and experimental evidence showing how opioids and psychostimulants can affect maternal behavior of drug-abusing mother and the development of their offspring., R. Šlamberová., and Obsahuje seznam literatury
We have analyzed the influence of altered thyroid hormone levels on changes of MyHC protein isoforms and their mRNA transcripts in the soleus muscle of 2-, 4- and 7-month-old euthyroid (EU), hypothyroid (HY) and hyperthyroid (TH) female inbred Lewis strain rats (methimazole and T3 treatment started 3 to 4 weeks after birth). We have found that the content of the dominant MyHC 1 isoform gradually increased in the EU rats and that this increase was more progressive in the HY rats at all three stages. On the other hand, in the TH rats the content of MyHC 1 isoform was the highest in the 2-month-old rats and it decreased with an increasing length of T3 treatment. The content of the minor 2a MyHC isoform followed the opposite pattern. In contrast to the protein isoforms, the MyHC mRNA transcripts remained at similar levels. Nevertheless, in general, the MyHC 1 mRNA level was decreased and MyHC 2a transcript increased in the TH rats, while the opposite changes occurred in the HY rats. Our results thus suggest that in the rat soleus muscle, both increased and decreased levels of thyroid hormones speed up the formation of an adult slow phenotype which is demonstrated by the precocious appearance of the slow MyHC 1 isoform, but opposite to the hypothyroid status, a longer T3 application promotes the expression of the faster MyHC 2a isoform., A. Vadászová-Soukup, T. Soukup., and Obsahuje bibliografii a bibliografické odkazy
In this study, we describe changes of plasma levels of the hypothalamic neuropeptide orexin A in obese children during the reduction of body weight and its relationship to other biochemical and anthropometrical parameters. We measured orexin A fasting plasma levels by the RIA method in 58 obese children - 33 girls and 25 boys; mean age 13.1±0.38 years (range 7-18.5) before and after 5 weeks of weight-reduction therapy. Leptin, IGF-1, and IGFBP-3 levels were measured in all the subjects and were compared to orexin A levels and anthropometrical data. Average weight in subjects before weight-reduction was 74.2±2.79 kg and after weight-loss 67.4±2.60 kg (p<0.0001). Orexin A levels before the therapy were 33.3±1.97 pg/ml and after the therapy 51.7±3.07 pg/ml (p<0.0001). Levels of orexin A were not significantly different between girls and boys (p=0.7842). We found negative correlation between orexin A and age (r = -0.5395; p<0.0001), body height (r = -0.4751; p=0.0002), body weight (r = -0.4030; p=0.0017) and BMI (r = -0.2607; p=0.0481). No correlation was found between orexin A and IGF-1, IGFBP-3 or leptin. Orexin A plasma levels increased during body weight loss, whereas the reverse was true for leptin levels. These findings support the hypothesis that orexin A may be involved in regulation of nutritional status in children., J. Bronský, J. Nedvídková, H. Zamrazilová, M. Pechová, M. Chada, K. Kotaška, J. Nevoral, R. Průša., and Obsahuje bibliografii a bibliografické odkazy
To specify the role of individual cytokines in the immune response to pyrogens, isolated and cultivated human peripheral blood mononuclear cells (PBMC) were used for the experiments. Different pyrogens (lipopolysaccharide from Escherichia coli - LPS and live Borrelia afzelii) were applied and the time course of changes in concentrations of different cytokines in the medium was followed using the ELISA method. It was found that nonstimulated human PBMC proliferate under in vitro conditions and produce IL-6, TNF-a, IL-10 and finally also IL-1b. Productions of IL-12 and INF-g are not changed. Proliferation of PBMC is potentiated after incubation with LPS or live Borrelia. PBMC stimulated by LPS increase the net production (stimulated minus unstimulated) of IL-1b and TNF-a significantly, while production of IL-6 was smaller. A delayed increase in the production of IL-10 was also observed. Productions of IL-12 and INF-g were not influenced. In contrast to LPS, stimulation of PBMC with live Borrelia, increases also the production of IL-12 and IFN-g, besides IL-1b, TNF-a, IL-6 and IL-10. Productions of IL-1b, IL-6 and TNFa increased immediately after incubation with both LPS and Borrelia, while productions of IL-12 and INF-g begin to increase 8 hours and production of IL-10 12 hours after stimulation. Data indicate that stimulation with different pyrogens may activate the cells of the immune cascade in a different way. Stimulation of BPMC by LPS seems to activate the initial steps of the immune response (macrophages and granulocytes) only, while infection with live Borrelia also stimulates the later phase of the immune response, probably due to effect of initially produced cytokines., L. Janský, P. Reymanová, J. Kopecký., and Obsahuje bibliografii
To specify the role of individual cytokines in the immune response to pyrogens, isolated and cultivated human peripheral blood mononuclear cells (PBMC) were used for the experiments. Different pyrogens (lipopolysaccharide from Escherichia coli - LPS and live Borrelia afzelii) were applied and the time course of changes in concentrations of different cytokines in the medium was followed using the ELISA method. It was found that nonstimulated human PBMC proliferate under in vitro conditions and produce IL-6, TNF-a, IL-10 and finally also IL-1b. Productions of IL-12 and INF-g are not changed. Proliferation of PBMC is potentiated after incubation with LPS or live Borrelia. PBMC stimulated by LPS increase the net production (stimulated minus unstimulated) of IL-1b and TNF-a significantly, while production of IL-6 was smaller. A delayed increase in the production of IL-10 was also observed. Productions of IL-12 and INF-g were not influenced. In contrast to LPS, stimulation of PBMC with live Borrelia, increases also the production of IL-12 and IFN-g, besides IL-1b, TNF-a, IL-6 and IL-10. Productions of IL-1b, IL-6 and TNFa increased immediately after incubation with both LPS and Borrelia, while productions of IL-12 and INF-g begin to increase 8 hours and production of IL-10 12 hours after stimulation. Data indicate that stimulation with different pyrogens may activate the cells of the immune cascade in a different way. Stimulation of BPMC by LPS seems to activate the initial steps of the immune response (macrophages and granulocytes) only, while infection with live Borrelia also stimulates the later phase of the immune response, probably due to effect of initially produced cytokines., L. Janský, P. Reymanová, J. Kopecký., and Obsahuje bibliografii
a1_Diabetes mellitus is a risk factor of cardiovascular diseases. ECG of patients with diabetes mellitus type 1 (DM 1) shows tachycardia (block of parasympathetic innervation) and abnormal repolarization (increased QT interval and QT dispersion (QTd)) indicating a risk of ventricular tachycardia and sudden death in young people with DM 1. The aim of the present report was to measure 145 parameters of the heart electric field in 22 patients (14 men, 8 women) with DM 1 without complications (mean age 32.8±11.4 years) and in 22 controls (11 men, 11 women, mean age 30.1±3.4 years). The duration of diabetes was 13.9 ±7.8 years. The parameters were regist ered by the diagnostic system Cardiag 112.2 and statistically evaluated by the Student and Mann-Whitney test. Tachycardia (86.3±2.7 beats.min-1), shortening of both QRS (79.9±1.6 ms) and QT (349.0±5.9 ms) and increased QT dispersion (115±36 ms) were observed in DM 1 when compared with the controls (75.0±2.1 beats. min -1, QRS 89.9±2.7 ms, QT 374.0±4.4 ms, QTd 34.0±12.0 ms, p<0.01). The QTc was 415.2±4.1 ms in DM 1 and 401.4±6.6 ms in controls (NS)., a2_Other significant findings in DM 1 were: higher maximum of depolarization isopotential maps (DIPMmax) in the initial phase of QRS and less positive in the terminal phase, more negative minimum (DIPMmin) during QRS similarly as the minimum in depolarization isointegral maps (DIIMmin) and the minimum in isointegral map of the Q wave (Q-IIMmin), lower maximum in repolarization isopotential maps (RIPMmax) and less negative minimum (RIPMmin), more negative amplitude of Q wave (Q-IPMAM) and more pronounced spread of depolarization (activation time). Our results confirmed a decreased parasympathetic to sympathetic tone ratio (tachycardia, shortening of the activation time) and revealed different depolarization and repolarization patterns in DM 1. The differences in heart electric field parameters measured by the BSPM method in DM 1 and in the controls indicate the importance of ECG examination of diabetic patients type 1 in the prevention of cardiovascular diseases., D. Žďárská, P. Pelíšková, J. Charvát, J. Slavíček, M. Mlček, E. Medová, O. Kittnar., and Obsahuje bibiografii a bibliografické odkazy
ECG body surface mapping (BSM) parameters in patients with diabetes mellitus Type 1 (DM1) are significantly different comparing to healthy non-diabetic subjects. Hypothesis that these changes are more pronounced in DM1 patients with autonomic neuropathy (AN) was tested. The parameters of BSM were registered by diagnostic system Cardiag 112.2 in 54 DM1 patients including 25 with AN and 30 control subjects. AN was diagnosed according to Ewing criteria when two or more Ewing tests were abnormal. In classic 12-lead ECG the heart rate was increased, QRS and QT shortened (p<0.01) and QTC prolonged in DM1 patients. The VCG measurement of QRS-STT angles and spatial QRS-STT angle showed non-significant differences. The absolute values of maximum and minimum in depolarization and repolarization isopotential, isointegral, isoarea maps were significantly different in DM1 patients in comparison with controls (p<0.01). The changes were more pronounced in DM1 patients with AN than in DM patients without AN (p<0.05). The QT duration measured in 82 leads of thorax was significantly shortened in 68 leads of both groups of DM 1 patients (p<0.01) when compared with controls. In 34 of them this shortening was more pronounced in DM1 patients with AN than in DM1 patients without AN (p<0.05). The results showed that the method of ECG BSM is capable to confirm the presence of autonomic neuropathy in diabetic patients., S. Palová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy