The aim of the study was to evaluate short-term heart rate variability (HRV) as an index of cardiac autonomic control in rats with lipopolysaccharide (LPS)-induced endotoxemia. Animals were injected intraperitoneally with LPS (100 μg/kg b.w.) and control group with an equivalent volume of saline. ECG recordings were done before (base) and 60, 120, 180, 240 and 300 min after LPS or saline administration. HRV magnitude was quantified by time and frequency-domain analysis (mean RR interval, SDRR, RMSSD, spectral powers in low (LF) and high frequency (HF) bands. Heart tissue homogenates and plasma were analyzed to determine interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and oxidative stress level (TBARS). Administration of lipopolysaccharide was followed by continuous rise in colonic body temperature compared to saline-treated controls. Endotoxemia in rats was accompanied by significant decrease in HRV spectral activity in high-frequency range at maximal body temperature (logHFpower: 1.2±0.5 vs. 1.9± 0.6 ms2, P<0.01). Increased IL-6 was found in heart tissue homogenates of LPS rats (8.0±0.6 vs. 26.4±4.8 pg/ml, (P<0.05). In conclusions, reduced HRV in HF band may indicate a decreased parasympathetic activity in LPS-induced endotoxemia as basic characteristics of altered cardiac control during response to endotoxemia., I. Zila, D. Mokra, J. Kopincova, M. Kolomaznik, M. Javorka, A. Calkovska., and Obsahuje bibliografii
Heart rate (HR) and heart rate variability (HRV) in newborns is influenced by genetic determinants, gestational and postnatal age, and other variables. Premature infants have a reduced HRV. In neonatal HRV evaluated by spectral analysis, a dominant activity can be found in low frequency (LF) band (combined parasympathetic and sympathetic component). During the first postnatal days the activity in the high frequency (HF) band (parasympat hetic component) rises, together with an increase in LF band and total HRV. Hypotrophy in newborn can cause less mature autonomic cardiac control with a higher contribution of sympathetic activity to HRV as demonstrated by sequence plot analysis. During quiet sleep (QS) in newborns HF oscillations increase - a phenomenon less expressed or missing in premature infants. In active sleep (AS), HRV is enhanced in contrast to reduced activity in HF band due to the rise of spectral activity in LF band. Comparison of the HR and HRV in newborns born by physiological vaginal delivery, without (VD) and with epidural anesthesia (EDA) and via sectio cesarea (SC) showed no significant differences in HR and in HRV time domain parameters. Analysis in the frequency domain re vealed, that the lowest sympathetic activity in chronotropic cardiac chronotropic regulation is in the VD group. Different neonatal pathological states can be associated with a reduction of HRV and an improvement in the health conditions is followed by ch anges in HRV what can be use as a possible prognostic marker. Examination of heart rate variability in neonatology can provide information on the maturity of the cardiac chronotropic regulation in early postnatal life, on postnatal adaptation and in pathological conditions about the potential dysregulation of cardiac function in newborns, especially in preterm infants., K. Javorka, Z. Lehotska, M. Kozar, Z. Uhrikova, B. Kolarovszki, M. Javorka, M. Zibolen., and Obsahuje bibliografii
This study aimed to investigate whether heat stress (HS) prevents a decrease in succinate dehydrogenase (SDH) activity and heat shock protein 60 (HSP60) and superoxide dismutase 2 (SOD2) contents in the extensor digitorum longus of streptozotocin (STZ)-induced diabetic rats. Twelve-week-old male Wistar rats were assigned to one of the four groups (n=6/group): control (Con), HS, diabetes mellitus (DM), and diabetes mellitus and heat stress (DM+HS). Diabetes was induced by the administration of STZ (50 mg/kg). HS was initiated 7 days after STZ treatment and performed at 42 °C for 30 min 5 times a week for 3 weeks. SDH activity was decreased in the DM and DM+HS groups. However, SDH activity was greater in the DM+HS group than in the DM group. Although HSP60 content was lower in the DM group than in the Con group, it was maintained in the DM+HS groups and was higher than that in the DM group. SOD2 content was decreased only in the DM group. These findings suggest that HS prevents the decrease in SDH activity in the skeletal muscle induced by DM. According to this mechanism, the maintenance of SOD2 and HSP60 by HS may suppress the increase in oxidative stress., K. Nonaka, S. Une, M. Komatsu, R. Yamaji, J. Akiyama., and Seznam literatury
Several members of the TGF-ß family are known to effectively regulate the fate of hematopoietic progenitor cells in a complex and context-dependent manner. Growth differentiation factor-15 (GDF15) is a divergent member of the TGF-ß family. This stress-induced cytokine has been proposed to possess immunomodulatory functions and its high expression is often associated with progression of a variety of pathological conditions. GDF15 is also induced by chemotherapy and irradiation. Very few fundamental studies have been published regarding the effect of GDF15 in hematopoiesis. In this study, we analyzed the hematological status of untreated and γ-irradiated mice deficient for GDF15 as a result of genetic knock-out (KO), in order to clarify the regulatory role of GDF15 in hematopoiesis. Significant differences between GDF15 KO mice and their pertinent WT controls were found in the parameters of blood monocyte numbers, blood platelet size, and distribution width, as well as in the values of bone marrow granulocyte/macrophage progenitor cells. Different tendencies of some hematological parameters in the GDF15 KO mice in normal conditions and those under exposure of the mice to ionizing radiation were registered. These findings are discussed in the context of the GDF15 gene function and its lack under conditions of radiation-induced damage., M. Hofer, Z. Hoferová, J. Remšík, M. Nováková, J. Procházková, R. Fedr, J. Kohoutek, L. Dušek, A. Hampl, K. Souček., and Obsahuje bibliografii
We investigated hematopoiesis in untreated and ionizing radiation-exposed cyclooxygenase-2-deficient (COX-2 KO) mice. We performed a complex hematological analysis of 16 parameters in untreated COX-2 KO male mice or COX-2 KO male mice irradiated with the dose of 4 Gy of γ-rays and their wildtype littermates. At baseline, hematopoiesis was increased in COX-2-deficient mice, but attenuated by irradation in COX-2- deficient mice compared to wildtype. To conclude, the antiinflammatory action of the COX-2 genetic disruption plays a positive role in hematopoiesis under basal conditions but is detrimental following radiation exposure., M. Hofer, Z. Hoferová L. Dušek, K. Souček, A. Gruzdev., and Obsahuje bibliografii
Extracorporeal life support (ECLS) is a treatment modality that provides prolonged blood circulation, gas exchange and can partially support or fully substitute functions of heart and lungs in patients with severe but potentially reversible cardiopulmonary failure refractory to conventional therapy. Due to high-volume bypass, the extracorporeal flow is interacting with native cardiac output. The pathophysiology of circulation and ECLS support reveals significant effects on arterial pressure waveforms, cardiac hemodynamics, and myocardial perfusion. Moreover, it is still subject of research, whether increasing stroke work caused by the extracorporeal flow is accompanied by adequate myocardial oxygen supply. The left ventricular (LV) pressure-volume mechanics are reflecting perfusion and loading conditions and these changes are dependent on the degree of the extracorporeal blood flow. By increasing the afterload, artificial circulation puts higher demands on heart work with increasing myocardial oxygen consumption. Further, this can lead to LV distention, pulmonary edema, and progression of heart failure. Multiple methods of LV decompression (atrial septostomy, active venting, intra-aortic balloon pump, pulsatility of flow) have been suggested to relieve LV overload but the main risk factors still remain unclear. In this context, it has been recommended to keep the rate of circulatory support as low as possible. Also, utilization of detailed hemodynamic monitoring has been suggested in order to avoid possible harm from excessive extracorporeal flow., Pavel Hála, Otomar Kittnar., and Obsahuje bibliografii
In this work, design and synthesis of high-molecular-weight N-(2- hydroxypropyl)methacrylamide-based polymer drug delivery systems tailored for cancer therapy is summarized. Moreover, the influence of their architecture on tumor accumulation and in vivo anti-cancer efficacy is discussed. Mainly, the high-molecularweight delivery systems, such as branched, grafted, multi-block, star-like or micellar systems, with molecular weights greater than the renal threshold are discussed and reviewed in detail., L. Kostka, T. Etrych., and Obsahuje bibliografii
A high VO2max in middle-age is related to high metabolic flexibility and lowered risk of metabolic diseases. However, the influence of a high VO2max induced by years of regular training in middle-age on protein expression related to muscle metabolism is not well studied. This study measures key proteins involved in mitochondrial oxidation, glucose and lipid metabolism in skeletal muscle of trained and untrained middle-aged men. 16 middle-aged men, matched for lean body mass, were recruited into an endurance trained (TR, n=8) or an untrained (CON, n=8) group based on their VO2max. A muscle biopsy was obtained from m. vastus lateralis and protein levels were analyzed by Western blotting. The TR had higher protein levels of mitochondrial complex III-V, endothelial lipase (EL) and perilipin 5 compared to the CON. Glycogen synthase (P=0.05), perilipin 3 (P=0.09) and ATGL (P=0.09) tended to be higher in TR than CON, but there was no difference in AKT I/II, HKII, GLUT4 and LPL protein expression. Lastly, there was a positive correlation between plasma HDL and EL (R2=0.53, P<0.01). In conclusion, a high VO2max in middle-aged men was as expected is reflected in higher muscle oxidative capacity, but also in higher endothelial lipase and perilipin 5 expression and a borderline higher glycogen synthase protein expression, which may contribute to a higher metabolic flexibility., A. Vigelsø, C. Prats, T. Ploug, F. Dela, J. W. Helge., 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