Given the potential clinical benefit of inhibiting Na+/Ca2+ exchanger (NCX) activity dur ing myocardial ischemia reperfusion (I/R), pharmacological approaches have been pursued to both inhibit and clarify the importance of this exchanger. SEA0400 was reported to have a potent NCX selectivity. Thus, we examined the effect of SEA0400 on NCX currents and I/R induced intracellular Ca2+ overload in mouse ventricular myocytes using patch clamp techniques and fluorescence measurements. Ischemia significantly inhibited inward and outward NCX current (from -0.04±0.01nA to 0 nA at -100 mV; from 0.23±0.08 nA to 0.11±0.03 nA at +50 mV, n=7). Subsequent reperfusion not only restored the current rapidly but enhanced the current amplitude obviously, especially the outward currents (from 0.23±0.08 nA to 0.49±0.12 nA at +50 mV, n=7). [Ca2+]i, expressed as the ratio of Fura-2 fluorescence intensity, increased to 138±7 % (P<0.01) during ischemia and to 210±11 % (P<0.01) after reperfusion. The change of NCX current and the increase of [Ca 2+]i during I/R can be blocked by SEA0400 in a dose-dependent manner with an EC50 value of 31 nM and 28 nM for the inward and outward NCX current, respectively. The results suggested that SEA0400 is a potent NCX inhibitor, which can protect mouse cardiac myocytes from Ca2+ overload during I/R injuries., J. Wang, Z. Zhang, Y. Hu, X. Hou, Q. Cui, Y. Zang, C. Wang., and Obsahuje bibliografii a bibliografické odkazy
The laboratory rat, a non-photoperiodic rodent, exhibits seasonal fluctuations of melatonin. Melatonin has been found to be readily transferred from the maternal to the fetal circulation. No data exist on the possible influence of maternal pineal gland upon seasonal variations of the offspring. The aim of the present study was to asses the influence of the maternal melatonin rhythm on the offspring postnatal development of the reproductive hormones LH, FSH and prolactin. Male offspring from control, pinealectomized (PIN-X) and PIN-X + melatonin (PIN-X+MEL) mother Wistar rats were studied at 21, 31, and 60 days of age. Seasonal age-dependent variations were found for all hormones studied in control offspring but PIN-X offspring showed a tendency to have reduced duration or altered seasonal variations. Maternal melatonin treatment to PIN-X mothers partially restored the effect of pinealectomy. The chronological study of LH, FSH, and prolactin in PIN-X offspring also showed an altered pattern as compared to control-offspring. Melatonin treatment to the mothers partially restored the developmental pattern of reproductive hormones. Results of this study indicate that maternal pineal gland of the laboratory rat is involved in the seasonal postnatal development variations of reproductive hormones of the offspring., N. Vásquez, E. Díaz, C. Fernández, V. Jiménez, A. Esquifino, B. Díaz., and Obsahuje bibliografii a bibliografické odkazy
The aim of the study was to evaluate serum α-glutathione S-transferase (s-GSTA) levels in patients with cystic fibrosis (CF) and to compare s-GSTA with other liver function tests and with a hepatic ultrasound scan (US). The cytosolic enzyme, a-glutathione S-transferase is predominantly found in the liver and is distributed uniformly in the liver tissue. In our study s-GSTA levels were measured in 37 CF patients aged 1 to 28 years (mean age 10.4 years, 24 males). The control group consisted of 27 patients aged 2 to 17 years (mean age 8.5 years, 18 males). The presence of hepatobiliary abnormalities was assessed by clinical examination, ultrasound scan, s-GSTA, and conventional liver enzymes: alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and g-glutamyl transferase (GMT). The calculated 5-95 % range of s-GSTA for the control group was 0.098-2.54 mg/l, for the CF group 0.43-9.76 mg/l. Mean s-GSTA level in the control group was 1.55 mg/l (S.D.=1.57), and 2.05 mg/l (S.D.=2.60) in the CF group. In the group of CF patients, the serum levels were significantly higher than in the control group (P<0.01). No significant correlation existed in the CF group between s-GSTA and conventional liver tests (ALT, AST, ALP and GMT). Four patients in the CF group had hepatobiliary abnormalities detectable by conventional liver tests, s-GSTA and US. Four patients had abnormal s-GSTA, while conventional liver tests and US were normal. One other patient had abnormal hepatic US, but normal standard liver tests and s-GSTA. The study has suggested that a raised s-GSTA level might be a marker of possible pathological changes of the hepatobiliar system in CF patients. Serum GSTA seems to be a more sensitive marker than transaminases for the monitoring of hepatocellular integrity and as an early predictor of hepatic damage., K. Šídlová, V. Skalická, K. Kotaška, M. Pechová, M. Chada, J. Bartošová , Z. Hříbal, J. Nevoral, V. Vávrová, R. Průša., and Obsahuje bibliografii
We have studied natural killer (NK) activity, lymphoproliferative response, the release of several cytokines (IL-2, TNFa and IL-1b) and the ROS production in peritoneal leukocytes obtained 0, 2, 4, 12 and 24 h after lipopolysaccharide (LPS) injection. Lethal septic shock (100 % mortality occurred at 30 h after LPS administration) was caused in female BALB/c mice by intraperitoneal injection of 100 mg/kg of E. coli LPS. Cytotoxicity and lymphoproliferation assay were preformed together with the measurement of IL-1b, IL-2 and TNFa production, and quantification of ROS. Natural killer activity, spontaneous lymphoproliferative response, IL-2, TNFa, IL-b release and ROS production were increased after LPS injection. In conclusions, ROS and proinflammatory mediators produced by immune cells in response to LPS are involved in the oxidative stress of endotoxic shock. This oxidative state alters some functional characteristics of leukocytes (proliferation and NK activity)., V. M. Víctor, M. De la Fuente., and Obsahuje bibliografii
To determine whether a short-term change in dietary habits affects postprandial lipemia in men and women in the same way, postprandial triglyceridemia was measured in age- and BMI-matched young healthy men and women after two weeks on the self-selected low-fat low-cholesterol (LF) diet and after another two weeks on the self-selected high-fat high-cholesterol (HF) diet. After a standardized challenge meal (1.4 g fat/kg of body weight), men had higher postprandial triglyceridemia than women on the HF diet but no such difference was observed on the LF diet. The results of this preliminary study suggest that there may be important sex differences in the mechanisms regulating the postprandial lipemia response to different diets, women being able to adapt better to the HF diet with respect to postprandial lipemia., J. Kovář, R. Poledne., and Obsahuje bibliografii
In our previous study, healthy volunteers showed considerable short-term dynamics and patterns of the coherence of high time resolution between respiratory movements (RESP), heart rate fluctuations (HRF), and arterial blood pressure fluctuations (BPF). These are physiological indicators of autonomic short-term coordination mediated mainly by the brainstem which could be impaired in severe brain disorders. We hypothesized a direct or indirect impairment of these functions by these disorders and examined these patterns in 16 patients suffering from severe brain disorders. We calculated partial and ordinary coherence sequences and found almost the same patterns of coherence sequences as in healthy volunteers, but a distinctly reduced frequency of pattern incidence in patients (2.8*1.5/10 min/patient and 9.5*2.8/10 min/subject, P<0.05). Furthermore, there is a significantly smaller frequency of HRF-related patterns in patients with poor outcome, compared with those in patients with good outcome (1.8*0.8/10 min/patient and 4.5*2.7/10 min/patient, P<0.05). We conclude that severe brain disorders reduce physiological short-term dynamics of autonomic coordination patterns in the mean values of patients, but not in every patient., U. Zwiener, Ch. Schelenz, S. Bramer, D. Hoyer., and Obsahuje bibliografii
The possible linear short-term coordination between respiratory movements (RESP), heart rate fluctuations (HRF), and arterial blood pressure fluctuations (BPF) in conscious human beings has not yet been investigated because of the restricted time resolution of conventional time series analysis. At present, this short-term dynamics as an expression of relative coordination can be quantified by newly developed adaptive autoregressive modeling of time series using Kalman filtering. Thus, in 6 conscious healthy volunteers, RESP, HRF, and BPF were recorded during 10 min in the supine position, at rest and during paced breathing. A considerable part of calculated ordinary and partial coherence sequences of short-term resolution between RESP and HRF, RESP and BPF, and partially between HRF and BPF showed patterns varying in time that could be correlated to changes between gradual coordinations (coherence changing between 0.40 and 0.95). They were more seldom complete or absent. There were mostly opposite changes between partial coherence sequences RESP-HRF/BPF and RESP-BPF/HRF demonstrating competitive behavior between these coordinations. Paced breathing did not essentially affect any observed characteristics. Therefore, these coherence dynamics are not essentially dependent on voluntary breathing movements. We conclude that to a different extent these linear and changing couplings between RESP, HRF, and BPF in conscious human beings exhibit properties of short-term complete and more frequently gradual coordinations showing dynamics that can not be determined by conventional methods., U. Zwiener, C. Schelenz, S. Bramer, D. Hoyer., and Obsahuje bibliografii
Ischemic postconditioning and remote conditioning are potentially useful tools for protecting ischemic myocardium. This study tested the hypothesis that 2,3-dehydrosilybin (DHS), a flavonolignan component of Silybum marianum , could attenuate cardiomyocyte damage following hypoxia/ reoxygenation by decreasing the generation of reactive oxygen species (ROS). After 5-6 days of cell culture in normoxic conditions the rat neonatal cardiomyocytes were divided into four groups. Control group (9 h at normoxic conditions), hypoxia/ reoxygenation group (3 h at 1 % O2 , 94 % N2 and 5 % CO2 followed by 10 min of 10 μmol·l -1 DHS and 6 h of reoxygenation in normoxia) and postconditioning group (3 h of hypoxia, three cycles of 5 min reoxygenation and 5 min hypoxia followed by 6 h of normoxia). Cell viability assess ed by propidium iodide staining was decreased after DHS treatment consistent with increased levels of lactatedehydrogenase (LDH) after reoxygenation. LDH leakage was significantly reduced when cardiomyocytes in the H/Re group were exposed to DHS. DHS treatment reduced H2O2 production and also decreased the generation of ROS in the H/Re group as evidenced by a fluorescence indicator. DHS treatment reduces reoxygenation-induced injury in cardiomyocytes by attenuation of ROS generation, H2O2 and protein carbonyls levels. In addition, we found that both the postconditioning protocol and the DHS treatment are associated with restored ratio of phosphorylated/total protein kinase C epsilon, relative to the H/Re group. In conclusion, our data support the protective role of DH S in hypoxia/reperfusion injury and indicate that DHS may act as a postconditioning mimic., E. Gabrielová, V. Křen, M. Jabůrek, M. Modrianský., and Obsahuje bibliografii
Aerobic exercise showed beneficial influence on cardiovascular systems in aging, and mechanisms underlying vascular adaption remain unclear. Large-conductance Ca2+ -activated K+(BKCa) channels play critical role s in regulating cellular excitability and vascular tone. This study determin ed the effects of aerobic exercise on aging -associated functional changes in BK Ca channels in cerebrovascular myocytes, Male Wistar rats aged 20- 22 mo nths were randomly assigned to sedentary (O -SED), low training frequency (O-EXL), and high training frequency group (O -EXH). Young rats were used as control. Compared to young rats, w hole -cell BK Ca current was decreased, and amplitude of spontaneous transient outward currents were reduced. The open probability and Ca2+/voltage sensitivity of single BK Ca channel were declined in O -SED, accompanied with a reduction of tamoxifen-induced BK Ca activation; the mean open time of BK Ca channels was shortened whereas close time was prolonged. Aerobic exercise training markedly alleviated the aging-associated decline independent of training frequency. Exercise three times rather than five times weekly may be a time and cost-saving training volume required to offer bene ficial effects to offset the functional declines of BK Ca during aging., Na Li, Bailin Liu, Sharon Xiang, Lijun Shi., and Obsahuje bibliografii
Sirtuin 1 (SIRT1) is involved in important biological processes such as energy metabolism and regulatory functions of the cell cycle, apoptosis, and inflammation. Our previous studies have shown hepatoprotective effect of polyphenolic compound resveratrol, which is also an activator of SIRT1. Therefore, the aim of our present study was to clarify the role of SIRT1 in process of hepatoprotection in animal model of drug-induced liver damage. Male Wistar rats were used for both in vivo and in vitro studies. Hepatotoxicity was induced by single dose of acetaminophen (APAP). Some rats and hepatocytes were treated by resveratrol or synthetic selective activator of sirtuin 1 (CAY10591). The degree of hepatotoxicity, the activity and expression of the SIRT1 were determined by biochemical, histological and molecular-biological assessments of gained samples (plasma, liver tissue, culture media and hepatocytes). Resveratrol and CAY attenuated APAP-induced hepatotoxicity in vivo and in vitro. Moreover, both drugs enhanced APAPreduced SIRT1 activity. Our results show that modulation of the SIRT1 activity plays a role in hepatoprotection. Synthetic activators of SIRT1 would help in understanding the role of SIRT1 and are therefore a major boost towards the search for specific treatment of liver disease., L. Wojnarová, N. Kutinová Canová, H. Farghali, T. Kučera., and Obsahuje bibliografii