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
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
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
Methylphenidate is commonly used for the treatment of attention deficit hyperactivity disorder. The cardiovascular safety of methylphenidate has been a subject of debate with some studies indicating that methylphenidate increases the likelihood of experiencing a myocardial infarction. However, it is unknown whether methylphenidate worsens the extent of injury during an ischemic insult. The purpose of this study was to determine whether short term exposure to methylphenidate increases the extent of myocardial injury during an ischemic insult. Male and female rats received methylphenidate (5 mg/kg/day) or saline for 10 days by oral gavage. Hearts were subjected to 20 min of ischemia and 2 h of reperfusion on a Langendorff isolated heart apparatus on day 11. Cardiac contractile function was monitored via an intraventricular balloon and myocardial injury was assessed by triphenyltetrazolium chloride staining. Methylphenidate significantly increased locomotor activity in male and female rats, confirming absorption of this psychostimulant into the central nervous system. Male hearts had significantly larger infarcts than female hearts, but methylphenidate had no impact on infarct size or postischemic recovery of contractile function in hearts of either sex. These data indicate that methylphenidate does not increase the extent of injury induced by an ischemic insult., Sarah L. Seeley, Manoranjan S. D’Souza, Thorne S. Stoops, Boyd R. Rorabaugh., and Obsahuje bibliografii
The aim of the present study was to investigate the effects of Angiotensin II (Ang II) and Arginin-Vasopressin (AVP) on contractility of non-pregnant uterus in diabetic Wistar rats and to explore whether one-week administration of Melatonin (MLT) or Ghrelin (GHR) will change the response of diabetic uterine muscle to AngII and AVP. Uterine horns, prepared by the method of isolated tissues were investigated as w ell as glycemic profile, blood pressure and body weight. The research of smooth muscle contractions was made by a new method of analysis, characterizing in detail the various phases of the myometrial activity. Differences in the development of the peptide-mediated smooth muscle contractions depending on the phase of the estrous cycle were observed. Experimental diabetes had a pronounced negative effect on force and time-parameters of AngII and AVP-stimulated uterine contractions. Administration of GHR or MLT had a beneficial effect on the glycemic status of diabetic rats and partially improved the response of uterine preparations to the peptides. The application of MLT increased both force and time-parameters of Ang II- and AVP-stimulated uterine contractions while treatment with GHR increased power characteristics and shortened contraction and relaxation of the smooth muscle process., T. Georgiev, A. Tolekova, R. Kalfin, P. Hadzhibozheva., and Obsahuje bibliografii
A number of clinical neurological pathologies are associated with increased permeability of the blood brain barrier (BBB). Induced changes of the homeostatic mechanisms in the brain microenvironment lead among others to cellular changes in the CNS. The question was whether some of these changes can be induced by osmotic opening of BBB in an in vivo experiment and whether they can be detected in cerebrospinal fluid (CSF). CSF was taken via the suboccipital puncture from 10 healthy rats and six rats after the osmotic opening of the BBB. In all 16 animals, concentration of myelin basic protein (MBP ng/ml), Neuron-specific enolase (NSE ng/ml) and Tau-protein (Tau pg/ml) were determined in CSF by ELISA. Values in both groups were statistically evaluated. Significant difference between the control and experimental group was revealed only for the concentration of myelin basic protein (p<0.01). The presented results indicate that osmotic opening of the BBB in vivo experiment without the presence of other pathological conditions of the brain leads to a damage of myelin, without impairment of neurons or their axons., P. Kozler, O. Sobek, J. Pokorný., 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
The cytoskeleton plays a key role in cellular proliferation, cellshape maintenance and internal cellular organization. Cells are highly sensitive to changes in microgravity, which can induce alterations in the distribution of the cytoskeletal and cell proliferation. This study aimed to assess the effects of simulated microgravity (SMG) on the proliferation and expression of major cell cycle-related regulators and cytoskeletal proteins in human umbilical cord mesenchymal stem cells (hucMSCs). A WST-1 assay showed that the proliferation of SMG-exposed hucMSCs was lower than a control group. Furthermore, flow cytometry analysis demonstrated that the percentage of SMG-exposed hucMSCs in the G0/G1 phase was higher than the control group. A western blot analysis revealed there was a downregulation of cyclin A1 and A2 expression in SMG-exposed hucMSCs as well. The expression of cyclin-dependent kinase 4 (cdk4) and 6 (cdk6) were also observed to be reduced in the SMG-exposed hucMSCs. The total nuclear intensity of SMG-exposed hucMSCs was also lower than the control group. However, there were no differences in the nuclear area or nuclear-shape value of hucMSCs from the SMG and control groups. A western blot and quantitative RT-PCR analysis showed that SMG-exposed hucMSCs experienced a downregulation of β-actin and α-tubulin compared to the control group. SMG generated the reorganization of microtubules and microfilaments in hucMSCs. Our study supports the idea that the downregulation of major cell cycle-related proteins and cytoskeletal proteins results in the remodeling of the cytoskeleton and the proliferation of hucMSCs., Ho Nguyen Quynh Chi, Hoang Nghia Son, Doan Chinh Chung, Le Dinh Huan, Tran Hong Diem, Le Thanh Long., 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