In the central nervous system (CNS), monocarboxylate transporter 1 (MCT1) is expressed in astrocytes and endothelial cells but also in oligodendroglia. Oligodendroglia support neurons and axons through lactate transportation by MCT1. Limited information is available on the MCT1 expression changes in candidate cells in the developing rat brain, especially in corpus callosum which is the most vulnerable area in demyelinating diseases. In the present study, we investigated the expression pattern of MCT1 during postnatal development in the rat corpus callosum using immunofluorescene staining, Western blotting analysis and RT-PCR. We reported that MCT1 gene and protein were consistently expressed in the rat corpus callosum from birth to adult. MCT1/CNPase and MCT1/GFAP immunofluorescence staining demonstrated that most of MCT1 positive cells were co-labeled with cyclic nucleotide 3′ phosphodiesterase (CNPase) in rat corpus callosum from P7 to adult, whereas MCT1+/GFAP+ cells preserve the dominate position before P7. Moreover, there were significant associations between the expression of MCT1 protein and the expression of myelin basic protein (MBP) (correlation coefficient: r=0.962, P=0.009) from P7 to adult. Similarly, the MCT1 mRNA expression was also significantly associated with MBP mRNA expression (r=0.976, P=0.005). Our results are proposing that in the developing brain white matter, MCT1 is predominately expressed in oligodendrocyte though it mainly expressed in astrocyte in early postnatal, which indicate that MCT1 may involve in the oligodendrocyte development and myelination., F. Dong, Y. Liu, Z. Zhang, R. Guo, L. Ma, X. Qu, H. Yu, H. Fan, R. Yao., and Obsahuje bibliografii
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
Neurodegenerative disorders, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), are increasing in prevalence. Currently, there are no effective and specific treatments for these disorders. Recently, positive effects of the orexigenic hormone ghrelin on memory and learning were demonstrated in mouse models of AD and PD. In this study, we tested the potential neuroprotective properties of a stable and long-lasting ghrelin analog, Dpr3ghrelin (Dpr3ghr), in SH-SY5Y neuroblastoma cells stressed with 1.2 mM methylglyoxal (MG), a toxic endogenous by-product of glycolysis, and we examined the impact of Dpr3ghr on apoptosis. Pre-treatment with both 10-5 and 10-7 M Dpr3ghr resulted in increased viability in SH-SY5Y cells (determined by MTT staining), as well as reduced cytotoxicity of MG in these cells (determined by LDH assay). Dpr3ghr increased viability by altering pro-apoptotic and viability markers: Bax was decreased, Bcl-2 was increased, and the Bax/Bcl-2 ratio was attenuated. The ghrelin receptor GHS-R1 and Dpr3ghr-induced activation of PBK/Akt were immuno-detected in SH-SY5Y cells to demonstrate the presence of GHS-R1 and GHS-R1 activation, respectively. We demonstrated that Dpr3ghr protected SH-SY5Y cells against MG-induced neurotoxicity and apoptosis. Our data suggest that stable ghrelin analogs may be candidates for the effective treatment of neurodegenerative disorders., A. Popelová, A. Kákonová, L. Hrubá, J. Kuneš, L. Maletínská, B. Železná., and Seznam literatury
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
Hypoventilation, as one of ventilatory disorders, decreases the electrical stability of the heart similarly as ischemia. If preconditioning by short cycles of ischemia has a cardioprotective effect against harmful influences of a prolonged ischemic period, then preconditioning by hypoventilation (HPC) can also have a similar effect. Anesthetized rats (ketamine 100 mg/kg + xylasine 15 mg/kg i.m., open chest experiments) were subjected to 20 min of hypoventilation followed by 20 min of reoxygenation (control group). The preconditioning (PC) was induced by one (1PC), two (2PC) or three (3PC) cycles of 5-min hypoventilation followed by 5-min reoxygenation. The electrical stability of the heart was measured by a ventricular arrhythmia threshold (VAT) tested by electrical stimulation of the right ventricle. Twenty-minute hypoventilation significantly decreased the VAT in the control and 1PC groups (p<0.05) and non-significantly in 2PC vs. the initial values. Reoxygenation reversed the VAT values to the initial level only in the control group. In 3PC, the VAT was increased from 2.32±0.69 mA to 4.25±1.31 mA. during hypoventilation (p<0.001) and to 4.37±1.99 mA during reoxygenation (p<0.001). It is concluded that cardioprotection against the hypoventilation/ reoxygenation-induced decrease of VAT proved to be effective only after three cycles of HPC., P. Švorc, I. Bračoková., and Obsahuje bibliografii
a1_A new concept of cardioprotection based on the exploitation of endogenous mechanisms is known as ischemic preconditioning (IPC). It has been hypothesized that substances released during brief ischemic stress (e.g. catecholamines) stimulate the receptors and trigger multiple cell signaling cascades. Opening of ATP-sensitive K+ channels [K(ATP)] has been suggested as a possible final step in the mechanisms of protection. In this study, the role of adrenergic activation was tested in Langendorff-perfused rat hearts subjected to test ischemia (TI; 30 min occlusion of LAD coronary artery) by: 1) mimicking IPC (5 min ischemia, 10 min reperfusion) with short-term (5 min) administration of norepinephrine (NE, 1 µM), 15 min prior to TI; 2) blockade with b- or a1-receptor antagonists, propranolol (10 µM) and prazosin (2 µM), respectively, applied 15 min prior to TI during IPC. The role of K(ATP) opening was examined by perfusion with a K(ATP) blocker glibenclamide (10 mM) during IPC. Both IPC and NE-induced PC effectively reduced the incidence of ventricular tachycardia (VT) to 33 % and 37 %, respectively, vs 100 % in the non-PC controls, whereby ventricular fibrillation (VF) was totally abolished by IPC and markedly suppressed by PC with NE (0 % and 10 %, respectively, vs 70 % in the non-PC hearts; P<0.05). The severity of arrhythmias (arrhythmia score, AS) was also markedly attenuated by both interventions (IPC: AS 1.7±0.4; NE-PC: AS 1.8±0.3 vs AS 4.1±0.2 in the controls; P<0.05). Protection was not suppressed by propranolol (VT 28 %; VF 14 %; AS 2.2±0.6), whereas prazosin reversed the protective effect of PC (VT 83 %; VF 67 %; AS 4.0±0.8). Antiarrhythmic protection afforded by NE-PC was abolished by pretreatment of rats with pertussis toxin (25 mg/kg, i.p.) given 48 h prior to the experiments., a2_Glibenclamide did not suppress the IPC-induced protection. In conclusion, the sensitivity of the rat heart to ischemic arrhythmias can be modulated by IPC. Protection is mediated via stimulation of a1-adrenergic receptors coupled with Gi-proteins but glibenclamide-sensitive K(ATP) channels do not appear to be involved in the mechanisms of antiarrhythmic protection in this model., T. Ravingerová, D. Pancza, A. Ziegelhoffer, J. Styk., and Obsahuje bibliografii
Our aim was to analyze the correlation of early postoperative cortisol levels in patients after transsphenoidal pituitary adenoma surgery compared to the standard dose ACTH test and Insulin tolerance test (ITT) several months later. We retrospectively reviewed data from 94 patients operated for pituitary adenoma in years 2009-2012. The comparison of day 7 (median) postoperative basal cortisol levels and 3.6 months (median) after pituitary adenoma surgery stimulation test - standard dose 250 μg 1-24ACTH test in 83 patients or ITT in 11 patients were performed. All 16 patients with early postoperative cortisol levels >500 nmol/l proved a sufficient response in the stimulation tests. At basal cortisol levels of 370-500 nmol/l the sufficient response was found in 96 % (27/28) of patients. In the postoperative basal cortisol levels 200-370 nmol/l we found a preserved corticotroph axis later on in 88 % (28/32) of cases. Patients with basal cortisol levels 100-200 nmol/l had a maintained corticotroph axis function in 8/11 cases - 73 %. All patients with an early postoperative basal cortisol level above 500 nmol/l proved in the stimulation tests a preserved corticotroph axis function. The interval 370-500 nmol/l showed a minimal risk of postoperative adrenal insufficiency., V. Hána Jr., J. Ježková, M. Kosák, M. Kršek, J. Marek, D. Netuka, M. Hil, V. Hána., and Obsahuje bibliografii
n previous studies, one of the systolic time intervals - preejection period (PEP) - was used as an index of sympathetic activity reflecting the cardiac contractility. However, PEP could be also influenced by several other cardiovascular variables including preload, afterload and diastolic blood pressure (DBP). The aim of this study was to assess the behavior of the PEP together with other potentially confounding cardiovascular system characteristics in healthy humans during mental and orthostatic stress (head-up tilt test - HUT). Forty-nine healthy volunteers (28 females, 21 males, mean age 18.6 years (SD=1.8 years)) participated in the study. We recorded finger arterial blood pressure by volume-clamp method (Finome ter Pro, FMS, Netherlands), PEP, thoracic fluid content (TFC) - a measure of preload, and cardiac output (CO) by impedance cardiography (CardioScreen ®2000, Medis, Germany). Systemic vascular resistance (SVR) - a measure of afterload - was calculated as a ratio of mean arterial pressure and CO. We observed that during HUT, an expected decrease in TFC was accompanied by an increase of PEP, an increase of SVR and no significant change in DBP. During mental stress, we observed a decrease of PEP and an increase of TFC, SVR and DBP. Correlating a change in assessed measures (delta values) between mental stress and previous supinerest, we found that ΔPEP correlated negatively with ΔCO and positively with ΔSVR. In orthostasis, no significant correlation between ΔPEP and ΔDBP, ΔTFC, ΔCO, ΔMBP or ΔSVR was found. We conclude that despite an expected increase of sympathetic activity during both challenges, PEP behaved differently indicating an effect of other confounding factors. To interpret PEP values properly, we recommend simultaneously to measure other variables influencing this cardiovascular measure., J. Krohova, B. Czippelova, Z. Turianikova, Z. Lazarova, I. Tonhajzerova, M. Javorka., and Obsahuje bibliografii