We have found that short-term statin treatment plus stem cell transplantation in acutely infarcted hearts improves cardiac function because statins promote the efficacy of cellular cardiomyoplasty. Autologous Sca-1+ LinCD45- (CXCR+ ) very small embryonic-like stem cell (VSEL) mobilization in acute myocardial infarction (AMI) correlates with the preservation of cardiac function. Whether short-term atorvastatin (Ator) can enhance the mobilization or recruitment of VSELs in AMI is still unclear. We divided mice into 4 groups: 1) sham; 2) AMI; 3) AMI+resveratrol (RSV) as a positive control; and 4) AMI+Ator. There was an increase in the circulating VSEL/full population of leukocytes (FPL) ratio 48 hours after AMI, and AMI+RSV increased it further. Ator administration did not increase the VSEL/FPL ratio. The cardiac stromal cell-derived factor-1 (SDF-1) and SDF-1α levels were in agreement with the results of VSEL mobilization. One week after AMI, more Sca-1+ CXCR+ cells were recruited to the myocardium of AMI+RSV mice but not AMI+Ator mice. Short-term Ator administration failed to upregulate cardiac SDF-1 and could not enhance the recruitment of VSELs early after AMI., H. Wang ... [et al.]., and Obsahuje seznam literatury
Statin-associated myopathy (SAM) represents a broad spectrum of disorders from insignificant myalgia to fatal rhabdomyolysis. Its frequency ranges from 1-5 % in clinical trials to 15-20 % in everyday clinical practice. To a large extent, these variations can be explained by the definition used. Thus, we propose a scoring system to classify statin-induced myopathy according to clinical and biochemical criteria as 1) possible, 2) probable or 3) definite. The etiology of this disorder remains poorly understood. Most probably, an underlying genetic cause is necessary for overt SAM to develop. Variants in a few gene groups that encode proteins involved in: i) statin metabolism and distribution (e.g. membrane transporters and enzymes; OATP1B1, ABCA1, MRP, CYP3A4), ii) coenzyme Q10 production (e.g. COQ10A and B), iii) energy metabolism of muscle tissue (e.g. PYGM, GAA, CPT2) and several others have been proposed as candidates which can predispose to SAM. Pharmacological properties of individual statin molecules (e.g. lipophilicity, excretion pathways) and patients´ characteristics influence the likelihood of SAM development. This review summarizes current data as well as our own results., M. Vrablik, L. Zlatohlavek, T. Stulc, V. Adamkova, M. Prusikova, L. Schwarzova, J. A. Hubacek, R. Ceska., and Obsahuje bibliografii
In this paper we analyze the use of statistics and associated problems, in three Czech biological journals in the year 2000. We investigated 23 articles Folia Biologica, 60 articles in Folia Microbiologica, and 88 articles in Physiological Research. The highest frequency of publications with statistical content have used descriptive statistics and t-test. The most usual mistake concerns the absence of reference about the used statistical software and insufficient description of the data. We have compared our results with the results of similar studies in some other medical journals. The use of important statistical methods is comparable with those used in most medical journals, the proportion of articles, in which the applied method is described insufficiently is moderately low., T. Pilčík., and Obsahuje bibliografii
Acetaminophen (APAP) overdose is the most common cause of acute liver failure in humans. Non-alcoholic fatty liver disease is the most frequent chronic liver disease in developed countries. The aim of our work was to compare the effect of APAP on intact rat hepatocytes and hepatocytes isolated from steatotic liver in primary cultures. Male Wistar rats were fed with standard diet (10 % energy from fat) and high-fat diet (71 % energy from fat) for 6 weeks and then hepatocytes were isolated. After cell attachment, APAP (1; 2.5; 3.75 and 5 mM) was added to culture media (William´s E medium) and hepatocytes were cultured for up to 24 hours. APAP caused more severe dose-dependent damage of steatotic hepatocytes as documented by increased release of lactate dehydrogenase (LDH) and LDH leakage, decreased activity of cellular dehydrogenases (WST-1 test) and reduced albumin production. Intact steatotic hepatocytes contained lower amount of reduced glutathione (GSH). Treatment with APAP (1 and 2.5 mmol/l) caused more pronounced decrease in GSH in steatotic hepatocytes. ROS (reactive oxygen species) formation after 24-hour incubation was significantly higher in fatty hepatocytes using APAP at concentration of 3.75 and 5 mmol/l. Interleukin 6 (IL-6) production was elevated in 2.5 mM APAP-treated nonsteatotic and steatotic hepatocyte cultures at 8 hours, compared to appropriate controls. In conclusions, our results indicate that steatotic hepatocytes exert higher sensitivity to the toxic action of APAP. This sensitivity may be caused by lower content of GSH in intact steatotic hepatocytes and by more pronounced APAPinduced decrease in intracellular concentration of GSH., O. Kučera, ... [et al.]., and Obsahuje seznam literatury
Stem cells biology is one of the most frequent topic of physiological research of today. Spinal fusion represents common bone biology challenge. It is the indicator of osteoinduction and new bone formation on ectopic model. The purpose of this study was to establish a simple model of spinal fusion based on a rat model including verification of the possible use of titanium microplates with hydroxyapatite scaffold combined with human bone marrow-derived mesenchymal stem cells (MSCs). Spinous processes of two adjacent vertebrae were fixed in 15 Wistar rats. The space between bony vertebral arches and spinous processes was either filled with augmentation material only and covered with a resorbable collagen membrane (Group 1), or filled with augmentation material loaded with 5 × 10 6 MSCs and covered with a resorbable collagen membrane (Group 2). The rats were sacrificed 8 weeks after the surgery. Histology, histomorphometry and micro-CT were performed. The new model of interspinous fusion was safe, easy, inexpensive, with zero mortality. We did not detect any substantial pathological changes or tumor formation after graft implantation. We observed a nonsignificant effect on the formation of new bone tissue between Group 1 and Group 2. In the group with MSCs (Group 2) we described mino r inflamatory response which indicates the imunomodulational and antiinflamatory role of MSCs. In conclusion, this new model proved to be easy to use in small animals like rats., K. Klíma, V. Vaněček, A. Kohout, O. Jiroušek, R. Foltán, J. Štulík, V. Machoň, G. Pavlíková, P. Jendelová, E. Syková, J. Šedý., and Obsahuje bibliografii
The determination of steroid hormones and subsequent interpretation of results is accompanied by a range of difficulties. The amount of information that current technology can provide on the circulating concentrations of more than a hundred various steroid compounds can lead to problems with interpretation. The aim of this study is to help provide orientation in this maze of data on steroid hormones. First we focus on specific aspects arising from the pre-analytical phase of steroid determination that need to be considered when planning sampling, whether for diagnostics or research. Then, we provide a brief summary of the characteristics and diagnostic relevance of several steroid hormones and/or their metabolites: pregnenolone, 17α-hydroxypregnenolone, dehydroepiandrosterone, hydroxyderivatives of dehydroepiandrosterone, androstenedione, testosterone, estrone, estradiol, estriol, cortisol, cortisone, which in our institute are determined with validated LC-MS/MS methods. For these steroids, we also provide newly calculated reference values in fertile women according to the phase of their menstrual cycle and Obsahuje bibliografii
Progesterone, estrogens, androgens and glucocorticoids all play important roles during pregnancy, from implantation to delivery. Focusing on selected steroid hormones in the peripartum period, we defined reference ranges measured using LS-MS/MS, and assessed relationships with maternal age, pregnancy weight gain, delivery type, and fetal sex. Samples were taken from 142 healthy women with physiological gravidity at the 37th week, during the first period of labor, and from newborn mixed cord blood. We found higher cortisol and 17-OH-pregnenolone plasma levels in mothers at the 37th week that carried male fetuses (p=0.03), but no significant differences in any studied hormones in newborns of different sex. Neither maternal age nor weight gain nor newborn birth weight had any relationships to any of the studied hormones. However, there were differences depending on vaginal versus planned cesarean section deliveries. In women carrying a male fetus we found significantly higher levels of 17-OH-pregnenolone, progesterone, cortisol, corticosterone and significantly lower levels of estradiol in those undergoing spontaneous vaginal delivery. However, we found no significant differences in the cord blood of newborn males from either delivery type. We established reference ranges for our analysis methods, which should be useful for further studies as well as in standard clinical practice., K. Adamcová, L. Kolátorová, T. Škodová, M. Šimková, A. Pařízek, L. Stárka, M. Dušková., and Obsahuje bibliografii
Normal pressure hydrocephalus (NPH) is one of a few treatable conditions of cognitive decline affecting predominately elderly people. Treatment, commonly based on the ventriculoperitoneal shunt insertion, leads to a partial or complete correction of patient's state, although its effect does not unfortunately always last. The aim of our study was to observe the changes of homocysteine and selected steroids and neurosteroids and follow-up the patients with respect to the duration of the NPH-related dementia improvement. The cerebrospinal fluid and plasma levels of cortisol, cortisone, dehydroepiandrosterone (DHEA), 7α-hydroxy-DHEA, 7β-hydroxy-DHEA, 7-oxo-DHEA, 16α-hydroxy-DHEA (all LC-MS/MS), DHEA-sulphate (DHEAS) (radioimmunoassay) and homocysteine (gas chromatography) were determined in NPH-diagnosed subjects before, during and 6, 12 and 24 months after shunt insertion. The cognitive functions ameliorated after shunt insertion and remain improved within 2 years. Changes in cerebrospinal fluid DHEAS, DHEA and its ratio, cortisone/cortisol and 16α-hydroxy-DHEA and plasma DHEAS, 7β-hydroxy-DHEA, cortisone/cortisol and homocysteine were found. Mentioned changes may contribute to the clarification of NPH pathogenesis. Altered neurosteroids levels are possible indicators to be utilized in the follow-up of NPH subjects. Moreover, plasma homocysteine may serve as an early indicator of NPH-related dementia., L. Sosvorova, M. Mohapl, M. Hill, L. Starka, M. Bicikova, J. Vitku, R. Kanceva, J. Bestak, R. Hampl., and Obsahuje bibliografii
Postpartum depression affects 10-15 % women after childbirth. There is no currently generally accepted theory about the causes and mechanisms of postpartum mental disorders. The principal hypothesis concerns the association with sudden changes in the production of hormones affecting the nervous system of the mother and, on the other hand, with the ability of receptor systems to adapt to these changes. We observed changes in steroidogenesis in the period ar ound spontaneous delivery. We collected three samples of maternal blood. The first sampling was 4 weeks prior to term; the second sampling was after the onset of uterine contractions (the beginning of spontaneous labour); the third sampling was during the third stage of labour (immediately after childbirth). Additionally, we collected mixed umbilical cord blood. The almost complete steroid metabolome was analyzed by gas chroma tography-mass spectrometry followed by RIA for some steroids. Mental changes in women in the peripartum period were observed using the Hamilton Depression Rating Scale. The local Ethics Committee approved the study. We found already th e changes in androgens levels correlating with postpartum mood disorders four weeks prior to childbirth. The strongest correlations between steroid and postpartum mood change were found in venous blood samples collected from mothers after childbirth and from umbilical cord blood. The main role played testosterone, possibly of maternal origin, and estrogens originating from the fetal compartment. These results suggest that change s in both maternal and fetal steroidogenesis are involved in the development of mental changes in the postpartum period. Descriptions of changes in steroidogenesis in relation to po stpartum depression could help clarify the causes of this disease, and changes in some steroid hormones are a promising marker of mental changes in the postpartum period., A. Pařízek, M. Mikešová, R: Jirák, M. Hill, M. Koucký, A. Pašková, M. Velíková, K. Adamcová, M. Šrámková, H. Jandíková, M. Dušková, L. Stárka., and Obsahuje bibliografii
The local concentration of glucocorticoids is intensively regulated by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD 1). Human 11β-HSD 1 also reversibly catalyzes the inter-conversion of 7α-hydroxy- and 7β-hydroxy-dehydroepiandrosterone (DHEA) into 7-oxo-DHEA. The cohort of 282 obese adolescents, 154 girls (median age 15.31 years, range 14.17-16.68 years) and 128 boys (median age 14.95 years, range 13.87-16.16 years), BMI (Body Mass Index) >90th percentile was examined. In samples collected before and after one month of reductive diet therapy, circulating levels of steroids were analyzed by liquid chromatography-tandem mass spectrometry and radioimmunoassay methods. The model of the treatment efficacy prediction was calculated. A significant reduction in circulating levels of cortisone, E2 and increased levels of 7β-hydroxy-DHEA after the reductive treatment was observed. Levels of cortisol, DHEA, DHT sustained without any significant change. The predictive Orthogonal Projections to Latent Structures (OPLS) model explained 20.1 % of variability of BMI, z-score change by the basal levels of 7α-hydroxy-DHEA, DHEA, cortisol and E2 as the strongest predictors. Reduced levels of circulating cortisone and reduced ratios of oxygenated/reduced metabolites reflect increased reductase activity of 11β-HSD 1 with reduced BMI, z-score. We hypothesize whether these changes can be attributed to the altered activity of 11β-HSD 1 in the liver., L. Máčová, L. Sosvorová, J. Vítků, M. Bičíková, M. Hill, H. Zamrazilová, B. Sedláčková, L. Stárka /., and Obsahuje bibliografii