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
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
Our aim was to investigate the influence of microgravity on the sensitivity of the skin to mechanical stimulation, epidermal thickness, peripheral nerve density in the upper dermis, and serum levels of a stress marker in a rat hindlimb suspension (HS) model. Thirty 8-week-old male Wistar rats were randomly divided into 3 groups: HS, n=10; sham HS, n=10; control, n=10. The suspension system was attached to rat tails in both the HS and sham-HS groups, but the hindlimbs were suspended only in the HS group. The HS and sham-HS groups were treated for 4 weeks. In behavioral tests using von-Frey filaments (n=5 in each group), mechanical hypersensitivity developed in the HS and sham HS groups. Serum corticosterone levels increased significantly in the HS and sham HS groups compared to the control group, and no changes in epidermal thickness or peripheral nerve density were observed immediately after the removal of HS (n=5 in each group). These data indicated that the mechanical hypersensitivity observed in the HS group was not caused by microgravity or inactivity, but rather by restraint stress. We suggest that microgravity does not affect skin sensitivity and histology in these animals., Y. Tanaka, ... [et al.]., and Obsahuje seznam literatury
The use of reversible lesion techniques in memory research was pioneered in the laboratory of Jan Bureš and Olga Burešova. We use the occasion of Jan’s 75th birthday to briefly review the experimental utility of this approach. Two experiments from our current research are reported in which reversible lesioning methods are used to ask otherwise experimentally untenable questions about memory retrieval. The first experiment used intra-hippocampal injections of tetrodotoxin to temporarily inactivate the hippocampus during retrieval of a well-learned place avoidance navigation memory. This revealed that the hippocampus is necessary for place avoidance retrieval but that the extinction of place avoidance can occur independently of retrieving the memory and intact hippocampal function. The second experiment used KCl-induced cortical spreading depression in an interhippocampal transfer paradigm to demonstrate that a Y-maze memory that is learned by only one cortical hemisphere can be made to transfer to the other hemisphere by forcing the rat to swim, a unique stressful experience that occurred in a different apparatus, different behavioral context, and involved different behaviors than the Y-maze training. This demonstrates, we believe for the first time behaviorally, that memories can be activated outside of the behavioral context of their acquisition and expression in rats., K. Ježek, M. Wesierska, A. A. Fenton., and Obsahuje bibliografii
Bretschneider (histidine-tryptophan-ketoglutarate) solution with its high histidine concentration (198 mM) is one of many cardioplegic solutions, which are routinely used for cardiac arrest. The aim of this study was to evaluate the physiological biochemical degradation of administered histidine to histamine and its major urinary metabolite N-methylimidazole acetic acid. A total number of thirteen consecutive patients scheduled for elective isolated coronary artery bypass grafting with cardiopulmonary bypass were enrolled in the prospective observational designed study at the Department of Thoracic and Cardiovascular Surgery between 04/2016 and 06/2016. Patients received 1.7 l Bretschneider solution on average. Before and at the end of operation as well as in the postoperative course, urine samples gathered from the urinary catheter bag were analyzed. During the operative period, urinary histidine concentration significantly increased from 29 μmol/mmol creatinine to 9,609 μmol/mmol creatinine. Postoperatively, histidine excretion reduced while histamine as well as N-methylimidazole acetic acid excretion rose significantly. Patients showed elevated levels of histidine, histamine as well as N-methylimidazole acetic acid in urine, but no unmanageable hemodynamic instability possibly arising from the histamine’s biological properties. Chemically modified histidine might reduce uptake and metabolization while maintaining the advantages of buffer capacity., J. K. Teloh, L. Ansorge, M. Petersen, E. Demircioglu, I. N. Waack, S. Brauckmann, H. Jakob, D.-S. Dohle., and Seznam literatury
Research and clinical implications on novel cardiac biomarkers has intensified significantly in the past few years. The highsensitive troponin T (hscTnT) assay plays a dominant role in diagnostic algorithm regarding myocardial injury in adults. Despite generally accepted use of hscTnT there are no data about physiological concentrations and cut-off limits in neonates and infants to date. The aim of this study is to assess hscTnT levels in healthy newborns and infants. Consecutively 454 healthy full termed newborns and 40 healthy infants were enrolled in the study. Samples of cord or venous blood were drawn and tested for hscTnT concentrations with high-sensitive TnT assay (Roche Cobas e602 immunochemical analyzer). The 97.5 percentile of hscTnT concentration was assessed and correlation analysis was performed in neonates. Two hundred and thirteen samples (47 %) were excluded due to blood hemolysis of various degrees in neonates. Finally, the group of 241 healthy newborns was statistically analyzed. The median concentration of hscTnT was 38.2 ng/ml, 97.5 percentile reached 83.0 ng/l (confidential interval 74.1 to 106.9 ng/l). HscTnT concentrations were statistically decreased in hemolytic samples when compared to non-hemolytic samples (34.3 ng/l [26.7 to 42.0 ng/l] and 37.1 ng/l [30.5 to 47.9 ng/l], respectively, p=0.003). Elevated plasma concentrations of hscTnT decreased to adult level within six months. This study has confirmed the higher reference levels of hscTnT in neonates and young infants when compared with adult population. Many extracardiac factors as hemolysis and age may affect the hscTnT level. Based on presented results, a careful clinical interpretation of hscTnT is recommended., P. Jehlička, M. Huml, D. Rajdl, A. Mocková, M. Matas, J. Dort, A. Masopustová., and Seznam literatury
Impressive advances in molecular genetic techniques allow to analyze the effects of natural selection on the development of human genome. For example, the trend towards blonde hair and blue eyes was documented. The approach to analyze possible effects of natural selection on the evolution of recent phenotypes with high risk of cardiovascular disease has not been described yet. A possible effect on the evolution of two main risk factors - hypercholesterolemia and hypertension - is presented. The close relationship of non-HDL cholesterol blood concentration to the proportion of pro-inflammatory macrophages in human visceral adipose tissue might be a result of long-lasting natural selection. Individuals with higher proportion of this phenotype might also display a higher ability to fight infection, which was very common in human setting from prehistory until Middle Ages. Successful battle against infections increased the probability to survive till reproductive age. Similar hypothesis was proposed to explain frequent hypertension in African Americans. A long-lasting selection for higher ability to conserve sodium during long-term adaptation to low sodium intake and hot weather was followed by a short-term (but very hard) natural selection of individuals during transatlantic slave transport. Only those with very high capability to retain sodium were able to survive. Natural selection of phenotypes with high plasma cholesterol concentration and/or high blood pressure is recently potentiated by high-fat high-sodium diet and overnutrition. This hypothesis is also supported by the advantage of familial hypercholesterolemia in the 19th century (at the time of high infection disease mortality) in contrast to the disadvantage of familial hypercholesterolemia during the actual period of high cardiovascular disease mortality., R. Poledne, J. Zicha., and Seznam literatury
To determine whether changes in partial pressure of CO2 participate in mechanism enlarging the lung functional residual capacity (FRC) during chronic hypoxia, we measured FRC and ventilation in rats exposed either to poikilocapnic (group H, FIO2 0.1, FICO2 <0.01) or hypercapnic (group H+CO2, FIO2 0.1, FICO2 0.04-0.05) hypoxia for the three weeks and in the controls (group C) breathing air. At the end of exposure a body plethysmograph was used to measure ventilatory parameters (V´E, fR, VT) and FRC during air breathing and acute hypoxia (10 % O2 in N2). The exposure to hypoxia for three weeks increased FRC measured during air breathing in both experimental groups (H: 3.0±0.1 ml, H+CO2: 3.1±0.2 ml, C: 1.8±0.2 ml). During the following acute hypoxia, we observed a significant increase of FRC in the controls (3.2±0.2 ml) and in both experimental groups (H: 3.5±0.2 ml, H+CO2: 3.6±0.2 ml). Because chronic hypoxia combined with chronic hypercapnia and chronic poikilocapnic hypoxia induced the same increase of FRC, we conclude that hypercapnia did not participate in the FRC enlargement during chronic hypoxia., H. Maxová, M. Vízek., and Obsahuje bibliografii
The aim of the study was to compare the effect of short-term hyperglycemia and short-term hyperinsulinemia on parameters of oxidative stress in Wistar rats. Twenty male rats (aged 3 months, average body weight 325 g) were tested by hyperinsulinemic clamp (100 IU/l) at two different glycemia levels (6 and 12 mmol/l). Further 20 rats were used as a control group infused with normal saline (instead of insulin) and 30 % glucose simultaneously. Measured parameters of oxidative stress were malondialdehyde (MDA), reduced glutathione (GSH) and total antioxidant capacity (AOC). AOC remained unchanged during hyperglycemia and hyperinsulinemia. Malondialdehyde (as a marker of lipid peroxidation) decreased significantly (p<0.05) during the euglycemic hyperinsulinemic clamp, and increased significantly during isolated hyperglycemia without hyperinsulinemia. Reduced glutathione decreased significantly (p<0.05) during hyperglycemia without hyperinsulinemia. These results suggest that the short-term exogenous hyperinsulinemia reduced the production of reactive oxygen species (ROS) during hyperglycemia in an animal model compared with the control group., P. Kyselová, M. Žourek, Z. Rušavý, L. Trefil, J. Racek., and Obsahuje bibliografii