The activation of metabotropic glutamate receptors subtype 4 (mGluR4) potentiates models of absence seizures in adult rats. These seizures are age-dependent, but data concerning the role of mGluR4 in immature brain is insufficient. N-phenyl-7- (hydroxyimino)cyclopropa[b]chromen-1acarboxamide (PHCCC), which is a positive allosteric modulator of these receptors, was used in three different models of seizures in immature rats: 1) convulsions induced by high doses of pentetrazol (PTZ; a model of generalised tonic-clonic seizures); 2) rhythmic electroencephalographic (EEG) activity induced by low doses of PTZ (a model of absence seizures); and 3) electrically elicited cortical afterdischarges (ADs, a model of myoclonic seizures). We administered four doses of PHCCC (1, 3, 10 and 20 mg/kg) in PTZ-induced convulsions and two doses (3 and 10 mg/kg) in the two electrophysiological models of freely moving rats with implanted electrodes. Every dose and age group consisted from 8 to 10 rats. PTZ-elicited convulsions were not significantly influenced by PHCCC. In contrast, PHCCC potentiated the effect of a subconvulsant dose (60 mg/kg) of PTZ. The 10-mg/kg dose of PHCCC significantly prolonged the duration of PTZ-induced rhythmic activity episodes and shortened the intervals between individual episodes in 25-day-old rats (P25). In contrast, this potentiation was not seen in P18 rats. Cortical ADs were significantly prolonged with repeated stimulations by both doses of PHCCC in P12 and P18 animals. P25 rats exhibited only slightly longer AD durations. In conclusion, we did not find any anticonvulsant effect of PHCCC. On the contrary, proconvulsant action was demonstrated in all three models in immature rats., E. Szczurowska, P. Mareš., and Obsahuje seznam literatury
Protein kinases, transcription factors and other apoptosis- and proliferation-related proteins can regulate reproduction, but their involvement in sexual maturation remains to be elucidated. The general aim of the in vivo and in vitro experiments with porcine ovarian granulosa cells was to identify possible intracellular regulators of female sexual maturation. For this purpose, proliferation (expression of proliferating cell nuclear antigen - PCNA, mitogen-activated protein kinases - ERK 1,2 related MAPK and cyclin B1), apoptosis (expression of the apoptotic protein Bax and apoptosis regulator Bcl-2 protein), expression of some protein kinases (cAMP dependent protein kinase - PKA, cGMPdependent protein kinase - PKG, tyrosine kinase - TK) and cAMP responsive element binding protein 1 (CREB-1) was examined in granulosa cells isolated from ovaries of immature and mature gilts. Expression of PCNA, ERK1,2 related MAPK, cyclin B1, Bcl-2, Bax, PKA, CREB-1, TK and PKG in porcine granulosa cells were detected by immunocytochemistry. Sexual maturation was associated with significant increase in the expression of Bcl-2, Bax, PKA, CREB-1 and TK and with decrease in the expression of ERK1,2 related MAPK, cyclin B1 and PKG in granulosa cells. No significant difference in PCNA expression was noted. The present data obtained from in vitro study indicate that sexual maturation in females is influenced by puberty-related changes in porcine ovarian signaling substances: increase in Bcl-2, Bax, PKA, CREB-1, TK and decrease in ERK1,2 related MAPK, cyclin B1 and PKG. It suggests that these signaling molecules could be potential regulators of porcine sexual maturation., A. Kolesarova, A. V. Sirotkin, M. Mellen, S. Roychoudhury., and Obsahuje bibliografii
Exposure to chronic hypoxia results in hypoxic pulmonary hypertension characterized by structural remodeling of peripheral pulmonary vasculature. An important part of this remodeling is an increase of collagen turnover and deposition of newly formed collagen fibrils in the vascular walls. The activity of collagenolytic metalloproteinases in the lung tissue is notably increased in the first days of exposure to hypoxia. The increased collagenolytic activity results in the appearance of collagen cleavages, which may be implied in the triggering of mesenchymal proliferation in peripheral pulmonary arteries. We hypothesize that radical injury to pulmonary vascular walls is involved in collagenolytic metalloproteinase activation., J. Novotná, J. Herget., and Obsahuje bibliografii
The aim was to find the differences in ketogenesis initiation in the early period after the exercise in obese patients and to find if these changes may predict the weig ht loss during the physical activity program. 96 females were enrolled. A clamped heart rate test (CHR) was performed to establish comparable exercise intensity. Blood samples for beta hydroxybutyrate (BOHB) assessment were collected prior, immediately after and 60 min after the test. Patients underwent a three month fitness program. Anthropometric measurements (fat mass and biochemical parameters) were measured. An energy intake was monitored and comparable in all subjects. A significant increase of BOHB was found in 60 th minute after the test, when compared with initiation levels (BOHB1 vs. BOHB3; p=0.03). This increase correlates with % fat mass (R=0.196; p=0.02) and negatively with age (R= –0.147; p=0.05) and with weight reduction during the three-month program (R= -0.299; p=0.03). Serum BOHB increase after the single exercise may detect individuals with an ability to induce lipolysis in three-month program of physical activity for obese patients., M. Matoulek, S. Svobododova, R. Vetrovska, Z. Stranska, S. Svačina., and Obsahuje bibliografii
Functional C(-260)→T polymorphism in the promoter of the CD14 gene has been reported to be associated with coronary heart disease (CHD). The functional role of the polymorphism, however, is still a matter of debate, since several studies have not proved its effect on clinical outcomes associated with atherosclerosis. Cardiovascular-related morbidity and mortality was assessed in a post-hoc approach four years after baseline characterization of patients (male/female n = 36/32) with angiographically proven coronary heart disease. CD14 C(-260)→T promoter genotype was determined at baseline. Seventeen out of 20 CHD patients with non-lethal cardiovascular events carried at least one T-allele. CD14 T-260 allele carriers have a 3.59-fold (95 % confidence interval: 1.11-6.75) increased risk for non-lethal cardiovascular events (Kaplan-Meier plot: log rank test p = 0. 029). All patients with lethal outcomes (n = 6) were also T-allele carriers. Multivariate logistic regression analysis among CHD patients including age, established risk factors and the C(-260)→T polymorphism as covariates and non-lethal events as a dependent variable confirmed the independent prospective effect of the T-allele on cardiovascular outcomes in this subset. Further evidence is provided for the role of CD14 C(-260)→T promoter polymorphism as a genetic susceptibility marker of atherosclerosis in patients with an advanced clinical course of the disease. Due to the small sample size and post-hoc character of the study large-scale prospective studies that monitor patients with proven CHD are needed to confirm these findings., M. Porsch-Öucürümez, J.Hucke, S. Westphal, J. A. Hubáček, G. Schmitz, C. Luley., and Obsahuje bibliografii a bibliografické odkazy
The activities of cytochrome c oxidase and FoF1-ATPase as well as the content of cytochromes cc1, aa3, and b were investigated in free brain mitochondria in the course of postnatal development and aging. The results show an increase of Vmax of both enzymes during postnatal development (between day 5 and 30). During the following phase ending at the age of 6 months, a decrease of FoF1-ATPase and cytochrome c oxidase activity occurs. From 6 to 12 months of age the activity of these enzymes did not change. The KM for both enzymes remained unchanged during the whole period observed. The content of cytochromes increased from the low values found in young rats, reached the highest values at around one month, and decreased till the age of 3 months. Later, their content in brain mitochondria did not markedly change. Our results suggest that the metabolic maturation of brain mitochondria differs in several aspects from the same process in other tissues, mainly in the time course. This is probably due to the unique role of neural tissue in the organism., M. Kalous, H. Rauchová, Z. Drahota., and Obsahuje bibliografii
The objective of this prospective double-blind study was to determine whether postoperative residual paralysis (PORP) after pancuronium or vecuronium results in hypoxemia and hypercapnia in the immediate admission period to the recovery ward. Eighty-three consecutive surgical patients received balanced or intravenous anesthesia with pancuronium for operations lasting longer than one hour or vecuronium for those lasting less than 60 min, both combined with neostigmine at the end of anesthesia. Standard clinical criteria assessed neuromuscular function intraoperatively. Postoperatively, we determined neuromuscular function (acceleromyography with supramaximal train-of-four (TOF) stimulation of the ulnar nerve, and a 5-s head lift) and pulmonary function (pulse oximetry: SpO2, and blood gas analysis: SaO2, PaCO2). We defined PORP as a TOF-ratio 70 %, hypoxemia as a postoperative SpO2³ 5 % below the pre-anesthestic level together with a postoperative SaO293 %, and hypercapnia as a PaCO2³ 46 mm Hg. Among the 49 pancuronium and 27 vecuronium patients studied, the PORP rates were 20 % in the pancuronium group and 7 % in the vecuronium group (p>0.05). Hypoxemia and hypercapnia occurred more often in pancuronium patients with PORP than in those without PORP namely 60 % vs. 10% (p<0.05) and 30 % vs. 8 % (p>0.05), respectively. We conclude that PORP after pancuronium is a significant risk factor for hypoxemia., U. Bissinger, F. Schimek, G. Lenz., and Obsahuje bibliografii
Free fatty acids (FFAs) are natural ligands of the PPARγ2 receptor. FFA plasma concentration and composition may represent one of the factors accounting for high heterogeneity of conclusions concerning the effect of the Pro12Ala on BMI, insulin sensitivity or diabetes type 2 (DM2) susceptibility. Our objective was to investigate the relation and possible interactions between the Pro12Ala polymorphism and FFA status, metabolic markers, and body composition in 324 lean nondiabetic subjects (M/F: 99/225; age 32±11 years; BMI 23.9±4.0 kg/m2) with and without family history of DM2. Family history of DM2 was associated with lower % PUFA and slightly higher % MUFA. The presence of Pro12Ala polymorphism was not associated with fasting plasma FFA concentration or composition, anthropometric or metabolic markers of glucose and lipid metabolism in tested population. However, the interaction of carriership status with FFA levels influenced the basal glucose levels, insulin sensitivity and disposition indices, triglycerides, HDL-cholesterol and leptin levels, especially in women. The metabolic effects of 12Ala carriership were influenced by FFA levels – the beneficial role of 12Ala was seen only in the presence of low concentration of plasma FFA. Surprisingly, a high PUFA/SFA ratio was associated with lower insulin sensitivity, the protective effect of 12Ala allele was apparent in subjects with family history of DM2. On the basis of our findings and published data we recommend the genotyping of diabetic patients for Pro12Ala polymorphism of the PPARγ2 gene before treatment with thiazolidinediones and education of subjects regarding diet and physical activity, which modulate metabolic outcomes., B. Bendlová, D. Vejražková, J. Včelák, P. Lukášová, D. Burkoňová, M. Kunešová, J. Vrbíková, K. Dvořáková, K. Vondra, M. Vaňková., and Obsahuje bibliografii a bibliografické odkazy