The purpose of the study was to describe and compare normal and 5-fluorouracil (5-FU)-suppressed hematopoiesis in adenosine A3 receptor knock-out (A3AR KO) mice and their wild-type (WT) counterparts. To meet the purpose, a complex hematological analysis comprising nineteen peripheral blood and bone marrow parameters was performed in the mice. Defects previously observed in the peripheral blood erythrocyte and thrombocyte parameters of the A3AR KO mice were confirmed. Compartments of the bone marrow progenitor cells for granulocytes/ macrophages and erythrocytes were enhanced in the control, as well as in the 5-FU-administered A3AR KO mice. 5-FU-induced hematopoietic suppression, evaluated on day 2 after the administration of the cytotoxic drug, was found to be significantly deeper in the A3AR KO mice compared with their WT counterparts, as measured at the level of the bone marrow progenitor cells. The rate of regeneration, as assessed between days 2 and 7 after 5-FU administration, was observed in the population of the granulocyte/macrophage progenitor cells to be higher in the A3AR KO mice in comparison with the WT ones. The increased depth of 5-FU-induced suppression in the compartments of the hematopoietic progenitor cells in the A3AR KO mice represents probably a hitherto undescribed further consequence of the lack of adenosine A3 receptors and indicates its synergism with the pharmacologically induced cytotoxic action of 5-FU., M. Hofer, M. Pospíšil, L. Dušek, Z. Hoferová, D. Komůrková., and Obsahuje bibliografii
Positive effects of repeated administration of diclofenac, an inhibitor of prostaglandin synthesis, in terms of prevention of tumor development and stimulation of hematopoiesis have been observed in C3H mice transplanted subcutaneously with G:5:113 fibrosarcoma cells. Fourteen-day treatment with diclofenac (3.75 mg/kg/day) started from day 5 after tumor cell transplantation. Measurements of tumors and hematological examinations were performed on day 30. The results strongly suggest the possibility that inhibitors of prostaglandin synthesis (non-steroidal anti-inflammatory drugs) may be used in oncological practice where the observed effects are highly desirable., M. Hofer, Z. Hoferová, P. Fedoročko, N. O. Macková., and Obsahuje bibliografii
Extracorporeal membranous oxygenation (ECMO) is increasingly used in the management of refractory cardiac arrest. Our aim was to investigate early effects of ECMO after prolonged cardiac arrest. In fully anesthetized swine (48 kg, N=18) ventricular fibrillation (VF) was induced and untreated period (20 min) of cardiac arrest commenced, followed by 60 min extracorporeal reperfusion (ECMO flow 100 ml/kg.min). Hemodynamics, arterial blood gasses, plasma potassium, tissue oximetry (StO2) and cardiac (EGM) and cerebral (BIS) electrophysiological parameters were continuously recorded and analyzed. Within 3 minutes of VF hemodynamic and oximetry parameters fall abruptly while metabolic parameters destabilize gradually over 20 minutes peaking at pH 7.04±0.05, pCO2 89±14 mmHg, K+ 8.5±1.6 mmol/l. During reperfusion most parameters restore rapidly: within 3-5 minutes mean arterial pressure reaches >40 mmHg, StO2 >50 %, paO2 >100 mmHg, pCO2 <50 mmHg, K+ <5 mmol/l. EGMs mean amplitude peaks at 4.5±2.4 min. Cerebral activity (BIS>60) reappeared in 5 animals after 87±21 min. In 12/18 animals return of spontaneous circulation was achieved. In conclusions, ECMO provides rapid restitution of internal milieu even after prolonged arrest. However, despite normalization of global parameters full recovery was not guaranteed since cardiac and cerebral electrical activities were sufficiently restored only in some animals. More sensitive and organ specific indicators need to be identified in order to estimate adequacy of cardiac support devices., M. Mlček, ... [et al.]., and Obsahuje seznam literatury
Operations in the pleural cavity are connected with circulatory changes in pulmonary circulation and general changes of hemodynamics. These changes are influenced by the position of patient’s body on the operation table and by the introduction of artificial pneumothorax. Thoracoscopy is an advanced surgical approach in thoracic surgery, but its hemodynamic effect is still not known. The aim of the present study was to compare the hemodynamic response to surgeries carried out by open (thoracotomy - TT) and closed (thoracoscopy - TS) surgical approach. Thirty-eight patients have been monitored throughout the operation - from the introduction of anesthesia to completing the surgery. Monitored parameters were systolic blood pressure (BPs), diastolic blood pressure (BPd), O2 saturation (SaO2), systolic blood pressure in pulmonary artery (BPPAs), diastolic blood pressure in pulmonary artery (BPPAd), wedge pressure (PW), central venous pressure in right atrium (CVP), cardiac output (CO) and total peripheral resistance (TPR). No significant difference has been found in hemodynamic response between TT and TS groups. Significant changes of hemodynamic parameters occurring during the whole surgical procedure were detected in both technical approaches. The most prominent changes were found after the position of patients was changed to the hip position (significantly decreased BPs, BPd, MAP, SaO2 and BPPAs) and 5 min after the pneumothorax was established (restoration of the cardiac output to the initial value and significant decrease of the TPR). It can be concluded that the thoracoscopy causes almost identical hemodynamic changes like the thoracotomy., S. Trča ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Acute liver failure (ALF) is a clinical syndrome resulting from widespread damage of hepatocytes, with extremely high mortality rate. Urgent orthotopic liver transplantation was shown to be the most effective therapy for ALF but this treatment option is limited by sca rcity of donor organs. Therefore, hepatocyte transplantation (Tx) has emerged as a new therapeutical measure for ALF, however, the first clinical applications proved unsatisfactory. Apparently, extensive preclinical studies are needed. Our aim was to exami ne if hepatocytes isolated from transgenic “firefly luciferase” Lewis rats into the recipient liver would attenuate the course of thioacetamide (TAA) -induced ALF in Lewis rats. Untreated Lewis rats after TAA administration showed a profound decrease in sur vival rate; no animal survived 54 h. The rats showed marked increases in plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, in plasma level of bilirubin and ammonia (NH 3 ), and in a significant decrease in plasma albumin. Hepatocyte Tx attenuated the course of TAA -induced ALF Lewis rats which was reflected by improved survival rate and reduced degree of liver injury showing as lowering of elevated plasma ALT, AST, NH 3 and bilirubin levels and increasing plasma albumin. In addition, bioluminescence imaging analyses have shown that in the TAA- damaged livers the transplanted hepatocyte were fully viable throughout the experiment. In conclusion, the results show that hepatocyte Tx into the liver can attenuate the course of TAA- induced ALF in Lewis rats. This information should be considered in attempts to develop new therapeutic approaches to the treatment of ALF., E. Koblihová, O. Lukšan, I. Mrázová, M. Ryska, L. Červenka., and Obsahuje bibliografii
Hepatoprotective properties of rooibos tea (Aspalathus linearis) were investigated in a rat model of liver injury induced by carbon tetrachloride (CCl4). Rooibos tea, like N-acetyl-L-cysteine which was used for the comparison, showed histological regression of steatosis and cirrhosis in the liver tissue with a significant inhibition of the increase of liver tissue concentrations of malondialdehyde, triacylglycerols and cholesterol. Simultaneously, rooibos tea significantly suppressed mainly the increase in plasma activities of aminotransferases (ALT, AST), alkaline phosphatase and billirubin concentrations, which are considered as markers of liver functional state. The antifibrotic effect in the experimental model of hepatic cirrhosis of rats suggests the use of rooibos tea as a plant hepatoprotector in the diet of patients with hepatopathies., O. Uličná, M. Greksák, O. Vančová, L. Zlatoš, Š. Galbavý, P. Božek, M. Nakano., and Obsahuje bibliografii
D-galactosamine is a hepatotoxic agent, which induces diffuse injury of liver tissue followed by the regeneration process. Our data showed a high increase of serum aminotransferases after D-galactosamine administration, which indicates a high extent of liver injury. When lipid emulsion was applied immediately after D-galactosamine, the increase of serum aminotransferases was greatly reduced. In addition, the decrease of the cytochrome c oxidase activity induced by D-galactosamine was not observed after lipid emulsion administration and the increase of total liver oxidative capacity in the regeneration period due to activated mitochondrial biogenesis was accelerated. All these findings indicate a protective effect of lipid emulsion administration against D-galactosamine toxicity., R. Ferenčíková, Z. Červinková, Z. Drahota., and Obsahuje bibliografii
Hepcidin is a key regulator of iron homeostasis, while hemojuvelin is an important component of the hepcidin regulation pathway. It has been recently proposed that soluble hemojuvelin, produced from hemojuvelin by the protease furin, decreases hepcidin expression. The aim of the presented study was to examine the downregulation of hepcidin by chronic bleeding in hemojuvelin-mutant mice. Male mice with targeted disruption of the hemojuvelin gene (Hjv-/- mice) and wild-type littermates were maintained on an iron-deficient diet and subjected to weekly phlebotomies for 7 weeks. Gene expression was examined by real-time PCR. In wild type mice, repeated bleeding decreased hepcidin mRNA by two orders of magnitude. In Hjv-/- mice, basal hepcidin expression was low; however, repeated bleeding also decreased hepcidin mRNA content by an order of magnitude. Phlebotomies reduced hepatic iron overload in Hjv-/- mice by 80 %. Liver and muscle furin mRNA content was not significantly changed. No effect on hepatic Tmprss6 mRNA content was observed. Results from the study indicate that soluble hemojuvelin is not the sole factor responsible for hepcidin downregulation. In addition, the presented data suggest that, under in vivo conditions, tissue hypoxia does not transcriptionally regulate the activity of furin or TMPRSS6 proteases., J. Krijt ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Hepcidin, a key regulator of iron metabolism, plays a crucial role in the pathogenesis of anemia of chronic disease. Although it is produced mainly in the liver, its recently described expression in adipose tissue has been shown to be enhanced in massive obesity due to chronic low-grade inflammation. Our objective was to study the changes in hepcidin expression in adipose tissue during acute-phase reaction. We measured hepcidin mRNA expression from isolated subcutaneous and epicardial adipose tissue at the beginning and at the end of the surgery. The expression of mRNAs for hepcidin and other iron-related genes (transferrin receptor 1, divalent metal transporter 1, ferritin, ferroportin) were measured by real-time RT-PCR. Hepcidin expression significantly increased at the end of the surgery in subcutaneous but not in epicardial adipose tissue. Apart from the increased levels of cytokines, the parameters of iron metabolism showed typical inflammation-induced changes. We suggest that acute inflammatory changes could affect the regulation of hepcidin expression in subcutaneous adipose tissue and thus possibly contribute to inflammation-induced systemic changes of iron metabolism., M. Vokurka ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Heterologous expression of Kir channels offers a tool to modulate excitability of neurons which provide insight into Kir channel functions in general. Inwardly-rectifying K+ channels (Kir channels) are potential candidate proteins to hyperpolarize neuronal cell membranes. However, heterologous expression of inwardly-rectifying K+ channels has previously proven to be difficult. This was mainly due to a high toxicity of the respective Kir channel expression. We investigated the putative role of a predominantly glial-expressed, weakly rectifying Kir channel (Kir4.1 channel subunit; KCNJ10) in modulating electrophysiological properties of a motoneuron-like cell culture (NSC-34). Transfection procedures using an EGFP-tagged Kir4.1 protein in this study proved to have no toxic effects on NSC-34 cells. Using whole cell-voltage clamp, a substantial increase of inward rectifying K+ currents as well as hyperpolarization of the cell membrane was observed in Kir4.1-transfected cells. Na+ inward currents, observed in NSC-34 controls, were absent in Kir4.1/EGFP motoneuronal cells. The Kir4.1-transfection did not influence the NaV1.6 sodium channel expression. This study demonstrates the general feasibility of a heterologous expression of a weakly inward-rectifying K+ channel (Kir4.1 subunit) and shows that in vitro overexpression of Kir4.1 shifts electrophysiological properties of neuronal cells to a more gliallike phenotype and may therefore be a candidate tool to dampen excitability of neurons in experimental paradigms., J. Zschüntzsch, ... [et al.]., and Obsahuje seznam literatury