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
For many important research topics in polymer science the use of radionuclides brings significant benefits concerning nanotechnology, polymer drug delivery systems, tissue engineering etc. This contribution describes important achievements of the radionuclide laboratory at Institute of Macromolecular Chemistry of the Academy of Sciences of the Czech Republic (IMC) in the area of polymers for biomedical applications. Particular emphasis will be given to water-soluble polymer carriers of radionuclides, thermoresponsive polymer radionuclide carriers, thermoresponsive polymers for local brachytherapy, polymer scaffolds modified with (radiolabeled) peptides and polymer copper chelators for the therapy of Wilson´s disease., M. Hrubý, J. Kučka, J. Pánek, P. Štěpánek., 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
The growth in the experimental research of facilities to support extracorporeal circulation requires the further development of models of acute heart failure that can be well controlled and reproduced. Two types of acute heart failure were examined in domestic pigs (Sus scrofa domestica ): a hypoxic model (n=5) with continuous perfusion of the left coronary artery by hypoxic deoxygenated blood and ischemic model (n=9) with proximal closure of the left coronary artery and controlled hypoperfusion behind the closure. The aim was a severe, stable heart pump failure defined by hemodynamic parameters changes: a) decrease in cardiac output by at least 50 %; b) decrease in mixed venous blood saturation to under 60 %; c) left ventricular ejection fraction below 25 %; and d) decrease in flow via the carotid arteries at least 50 %. Acute heart failure developed in the first group in one animal with no acute mortality and in the second group in 8 animals with no acute mortality. In the case of ischemic model the cardiac output fell from 6.70±0.89 l/min to 2.89±0.75 l/min. The saturation of the mixed venous blood decreased from 83±2 % to 58±8 %. The left ventricular ejection fraction decreased from 50±8 % to 19±2 %. The flow via the carotid arteries decreased from 337±78 ml/min to 136±59 ml/min (P≤0.001 for all comparisons). The proposed ischemic model is not burdened with acute mortality in the development of heart failure and is suitable for further use in experimental research into extracorporeal circulatory support., S. Lacko, M. Mlček, P. Hála, M. Popková, D. Janák, M. Hrachovina, J. Kudlička, V. Hrachovina, P. Ošťádal, O. Kittnar., and Obsahuje bibliografii
The aim of our study was to characterize resistance to ischemia/reperfusion (I/R) injury in Langendorff-perfused rat hearts and effectivity of ischemic preconditioning (PC) under condition of simulated acute hyperglycemia (SAHG) by perfusion of the hearts with Krebs-Henseleit (KH) solution with elevated glucose concentration (22 mmol/l). I/R injury was induced by 30- min coronary occlusion followed by 120-min reperfusion and PC by two cycles of 5-min occlusion/5-min reperfusion, prior to I/R. The severity of I/R injury was characterized by determination of the size of infarction (IS, expressed in % of area at risk size) and the amount of heart-type fatty acid binding protein (h-FABP, a marker of cell injury) released from the hearts to the effluent. Significantly smaller IS (8.8±1 %) and lower total amount of released h-FABP (1808±660 pmol) in PC group compared with IS 17.1±1.2 % (p<0.01) and amount of h-FABP (8803±2415 pmol, p<0.05) in the non-PC control hearts perfused with standard KH solution (glucose 11 mmol/l) confirmed protective effects of PC. In contrast, in SAHG groups, PC enhanced IS (21.4±2.2 vs. 14.3±1.3 %, p<0.05) and increased total amount of h-FABP (5541±229 vs. 3458±283 pmol, p<0.05) compared with respective non-PC controls. Results suggest that PC has negative effect on resistance of the hearts to I/R injury under conditions of elevated glucose in vitro., M. Zálešák, P. Blažíček, D. Pancza, V. Ledvényiová, M. Barteková, M. Nemčeková, S. Čarnická, A. Ziegelhöffer, T. Ravingerová., and Obsahuje bibliografii
The Morris water maze (MWM) is one of the most common tasks used to assess spatial learning and memory ability in rodents. Genetic strain and gender are two prominent variants that influence spatial performance. Although it was reported that ICR (Institute of Cancer Research) mice exhibited an unchanged baseline performance in the training phase of the MWM task, this outbred strain has been widely used in learning and memory studies, and little is known regarding the effects of sex on behavioral performance. In this study, we demonstrated that both male and female ICR mice could complete the MWM task. Furthermore, a significant sex difference was observed, with females having shorter escape latencies and longer durations in the target quadrant in both the acquisition and test phases. Our findings emphasize the necessity of careful examination of not only the strain effect on behavioral performance but also the sex effect., J.-F. Ge, ... [et al.]., and Obsahuje seznam literatury
Maternal hyperandrogenism during pregnancy might have metabolic and endocrine consequences on the offspring as shown for the polycystic ovary syndrome. Despite numerous experiments, the impact of prenatal hyperandrogenic environment on postnatal sex steroid milieu is not yet clear. In this study, we investigated the effect of prenatal testosterone excess on postnatal concentrations of luteinizing hormone, corticosterone and steroid hormones including testosterone, pregnenolone, progesterone, estradiol and 7β-hydroxyepiandrosterone in the offspring of both sexes. Pregnant rats were injected daily with either testosterone propionate or vehicle from gestational day 14 until parturition. The hormones were evaluated in plasma of the adult offspring. As expected, females had lower testosterone and higher pregnenolone, progesterone and estradiol in comparison to males. In addition, corticosterone was higher in females than in males, and it was further elevated by prenatal testosterone treatment. In males, prenatal testosterone exposure resulted in higher 7β-hydroxyepiandrosterone in comparison to control group. None of the other analyzed hormones were affected by prenatal testosterone. In conclusion, our results did not show major effects on sex hormone production or luteinizing hormone release in adult rats resulting from testosterone excess during their fetal development. However, maternal hyperandrogenism seems to partially affect steroid biosynthesis in sex-specific manner., E. Domonkos, V. Borbélyová, L. Kolátorová, T. Chlupáčová, D. Ostatníková, J. Hodosy, L. Stárka, P. Celec., 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
Acute liver failure (ALF) is a clinical syndrome with high mortality rate, resulting from widespread hepatocyte damage. Its pathophysiological background is still poorly understood and preclinical studies evaluating pathophysiology and new potential therapeutic measures are needed. The model of ALF induced by administration of thioacetamide (TAA) in Lewis rats is recommended as optimal; however, the limitation of previous studies was that they were performed predominantly in male rats. In view of the growing recognition that sex as a biological variable should be taken into consideration in preclinical research, we examined its role in the development of TAA-induced ALF in Lewis rats. We found that, first, intact male Lewis rats showed lower survival rate than their female counterparts, due to augmented liver injury documented by higher plasma ammonia, and bilirubin levels and alanine aminotransferase activity. Second, in female rats castration did not alter the course of TAA-induced ALF whereas in the male gonadectomy improved the survival rate and attenuated liver injury, reducing it to levels observed in their female counterparts. In conclusion, we found that Lewis rats show a remarkable sexual dimorphism with respect to TAA-induced ALF, and male rats display dramatically poorer prognosis as compared with the females. We showed that testosterone is responsible for the deterioration of the course of TAA-induced ALF in male rats. In most general terms, our findings indicate that in the preclinical studies of the pathophysiology and treatment of ALF (at least of the TAA-induced form) the sex-linked differences should be seriously considered., Eva Koblihová, Iveta Mrázová, Zdenka Vaňourková, Hana Maxová, Miroslav Ryska, Jiří Froněk., and Obsahuje bibliografii