The complex architecture of the liv er biliary network represents a structural prerequisite for the formation and secretion of bile as well as excretion of toxic substances through bile ducts. Disorders of the biliary tract affect a significant portion of the worldwide population, often leading to cholestatic liver diseases. Cholestatic liver disease is a condition that results from an impairment of bile formation or bile flow to the gallbladder and duodenum. Cholestasis leads to dramatic changes in biliary tree architecture, worsening liver disease and systemic illness. Recent studies show that the preva lence of cholestatic liver diseases is increasing. The availability of well characterized animal models, as well as development of visualization approaches constitutes a critical asset to develop novel pathogenetic concepts and new treatment strategies., L. Sarnova, M. Gregor., and Obsahuje bibliografii
Primary graft dysfunction (PGD) is a life-threatening complication among heart transplant recipients and a major cause of early mortality. Although the pathogenesis of PGD is still unclear, ischemia/reperfusion injury has been identified as a predominant factor. Both necrosis and apoptosis contribute to the loss of cardiomyocytes during ischemia/reperfusion injury, and this loss of cells can ultimately lead to PGD. The aim of our prospective study was to find out whether cell death, necrosis and apoptosis markers present in the donor myocardium can predict PGD. The prospective study involved 64 consecutive patients who underwent orthotopic heart transplantation at our institute between September 2010 and January 2013. High-sensitive cardiac troponin T (hs-cTnT) as a marker of minor myocardial necrosis was detected from arterial blood samples before the donor’s pericardium was opened. Apoptosis (caspase-3, active + pro-caspase-3, bcl-2, TUNEL) was assessed from bioptic samples taken from the right ventricle prior graft harvesting. In our study, 14 % of transplant recipients developed PGD classified according to the standardized definition proposed by the ISHLT Working Group. We did not find differences between the groups in regard to hs-cTnT serum levels. The mean hs-cTnT value for the PGD group was 57.4±22.9 ng/l, compared to 68.4±10.8 ng/l in the group without PGD. The presence and severity of apoptosis in grafted hearts did not differ between grafts without PGD and hearts that subsequently developed PGD. In conclusion, our findings did not demonstrate any association between measured myocardial cell death, necrosis or apoptosis markers in donor myocardium and PGD in allograft recipients. More detailed investigations of cell death signaling pathways in transplanted hearts are required., O. Szarszoi, J. Besik, M. Smetana, J. Maly, M. Urban, J. Maluskova, A. Lodererova, L. Hoskova, Z. Tucanova, J. Pirk, I. Netuka., and Obsahuje bibliografii
The goal of the research is to investigate the special effect of ovarian-menstrual cycle phases on the level of women’s blood pressure and characteristics of Mayer waves. 77 women aged 18-19 were tested under condition close to the state of basal metabolism in follicular phase (I), ovulation (II) and luteal phase (III) of ovarian-menstrual cycle. In phases II and III, the increase of mean and diastolic blood pressure level, in comparison with phase I in the prone position at rest and with psycho-emotional loading, were observed. The distinctions between variation parameters of R-R interval duration, stroke volume and its synchronization in phases II and III, in comparison with phase I, were observed in the prone position at rest, during tilt-test and with psycho-emotional loading. The substantial level of relationship between the power of Mayer waves and mean and diastolic blood pressure, mainly in phase I under conditions of all types, is observed. The maximum peak amplitude of stroke volume spectrogram is associated with pressure levels in the range of 0.04-0.15 Hz (ρ from -0.33 to -0.64). The obtained results indicate the possible participation of spontaneous baroreflex sensitivity characteristics in keeping blood pressure level in women., O. I. Lutsenko, S. O. Kovalenko., and Obsahuje bibliografii
Type 2 diabetes mellitus (T2DM) is associated with increased fracture risk; the underlying mechanism remains unexplained. This study aimed to investigate the relationships between body composition and bone and glucose metabolism in postmenopausal women wit h T2DM. Dual-energy X-ray absorptiometry was used to measure bone mineral density (BMD) and body composition. A total of 68 postme nopausal women with T2DM and 71 controls were eligible for the study. In contrast to normal BMD in T2DM, a similar prevalence of low-trauma fractures was observed in both groups. T2DM women had significantly higher Trunk fat% and A/G ratio and significantly lower Legs LM% and Legs FM%. Legs LM% was significantly lower in fractured T2DM group and negatively correlated with glycaem ia and HbA1c (p<0.01). Serum osteocalcin was significantly lower in T2DM and inversely correlated with FM%, Trunk FM% and A/G ratio (p<0.01) and positively correlated with Legs FM% and total LM% (p<0.05). In conclusion, abdominal obesity and decrease in mu scle mass may contribute to low bone formation in T2DM women. Further research is needed to unravel underlying pathophysiological mechanisms and to determine whether maintenance of muscle mass, especially in the lower extremities and/or reduction of centra l fat mass can prevent fractures., I. Raška Jr., M. Rašková, V. Zikán, J. Škrha., and Obsahuje bibliografii
The aim of the current study was to clarify the effect of high sucrose diet (HSD) on bile formation (BF) in rats with hereditary hypertriglyceridemia (HHTg). Potentially positive effects were studied for boldine, a natural choleretic agent. Administration of HSD to HHTg rats led to increased triglyceride deposition in the liver. HSD reduced BF as a consequence of decreased biliary secretion of bile acids (BA) and glutathione. Responsible mechanism was down-regulation of hepatic transporters for BA and glutathione, Bsep and Mrp2, respectively. Moreover, gene expressions of transporters for other constituents of bile, namely Abcg5/8 for cholesterol, Abcb4 for phospholipids, and Oatp1a4 for xenobiotics, were also reduced by HSD. Boldine partially attenuated cholestatic effect of HSD by promotion of biliary secretion of BA through up-regulation of Bsep and Ntcp, and by increase in biliary secretion of glutathione as a consequence of its increased hepatic disposition. This study demonstrates mechanisms of impaired BF during nonalcoholic fatty liver disease induced by HSD. Altered function of responsible transporters suggests also potential for changes in kinetics of drugs, which may complicate pharmacotherapy in subjects with high intake of sucrose, and with fatty liver disease. Sucrose induced alterations in BF may be alleviated by administration of boldine., M. Zagorova, A. Prasnicka, Z. Kadova, E. Dolezelova, L. Kazdova, J. Cermanova, L. Rozkydalova, M. Hroch, J. Mokry, S. Micuda., and Obsahuje bibliografii
We aimed to investigate the effects of brain-derived neurotrophic factor (BDNF) on apoptosis of intestinal epithelial cells (IECs) and alterations of intestinal barrier integrity using BDNF knock-out mice model. Colonic tissues from BDNF+/+ mice and BDNF+/- mice were prepared for this study. The integrity of colonic mucosa was evaluated by measuring trans-mucosa electrical resistance and tissue conductance in Ussing chamber. The colonic epithelial structure was analyzed by transmission electron microscopy. Apoptosis involvement was determined with TUNEL staining, active caspase-3 immunostaining and Western blotting for the protein expression of active caspase-3, Bax and Bcl-2. The expression levels and distribution of tight junction proteins were evaluated by immunohistochemistry or Western blots. Compared with BDNF+/+ mice, BDNF+/- mice displayed impaired integrity and ultrastructure alterations in their colonic mucosa, which was characterized by diminished microvilli, mitochondrial swelling and epithelial cells apoptosis. Altered intestinal barrier function was linked to excessive apoptosis of IECs demonstrated by the higher proportion of TUNEL-positive apoptotic cells and enhanced caspase activities in BDNF+/- mice. Increased expression of Bax and claudin-2 proteins and reduced Bcl-2 and tight junction proteins (occludin, ZO-1 and claudin-1) expression were also detected in the colonic mucosa of BDNF+/- mice. BDNF may play a role in the maintenance of intestinal barrier integrity via its anti-apoptotic properties., Dong-Yan Zhao, Wen-Xue Zhang, Qing-Qing Qi, Xin Long, Xia Li, Yan-Bo Yu, Xiu-Li Zuo., and Obsahuje bibliografii
Ruminants are often fed a high-concentrate (HC) diet to meet lactating demands, yet long-term concentrate feeding induces subacute ruminal acidosis (SARA) and leads to a decrease in milk fat. Buffering agent could enhance the acid base buffer capacity and has been used to prevent ruminant rumen SARA and improve the content of milk fat. Therefore, we tested whether a buffering agent increases lipid anabolism in the livers of goats and influences of milk fat synthesis. Twelve Saanen-lactating goats were randomly assigned to two groups: one group received a HC diet (Concentrate: Forage=60:40, Control) and the other group received the same diet with a buffering agent added (10 g sodium butyrate, C4H7NaO2; 10 g sodium bicarbonate, NaHCO3; BG) over a 20-week experimental period. Overall, milk fat increase (4.25±0.08 vs. 3.24±0.10; P<0.05), and lipopolysaccharide levels in the jugular (1.82±0.14 vs. 3.76±0.33) and rumen fluid (23,340±134 vs. 42,550±136) decreased in the buffering agent group (P<0.05). Liver consumption and release of nonesterified fatty acid (NEFA) into the bloodstream increased (P<0.05). Phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and ribosomal protein S6 kinase (p70S6K) up-regulated significantly in the livers of the buffering agent group (P<0.05). It also up-regulated expression of the transcription factor sterol regulatory element binding protein-1c (SREBP-1c) and its downstream targets involved in fatty acid synthetic, including fatty acid synthetase (FAS), stearoyl-CoA desaturase (SCD-1) and acetyl-CoA carboxylase 1 (ACC1) (P<0.05). The BG diet increased insulin levels in blood (19.43±0.18 vs. 13.81±0.10, P<0.05), and insulin receptor was likewise elevated in the liver (P<0.05). Cumulatively, the BG diet increased plasma concentrations of NEFA by INS-PI3K/AKTSREBP- 1c signaling pathway promoting their synthesis in the liver., L. Li, M. L. He, K. Wang, Y. S. Zhang., and Obsahuje bibliografii
Dairy goats are often fed a high-concentrate (HC) diet to meet their lactation demands; however, long-term concentrate feeding is unhealthy and leads to milk yield and lactose content decreases. Therefore, we tested whether a buffering agent is able to increase the output of glucose in the liver and influence lactose synthesis. Eight lactating goats were randomly assigned to two groups: one group received a HC diet (Concentrate : Forage = 6:4, HG) and the other group received the same diet with a buffering agent added (0.2 % NaHCO3, 0.1 % MgO, BG) over a 19-week experimental period. The total volatile fatty acids and lipopolysaccharide (LPS) declined in the rumen, which led the rumen pH to become stabile in the BG goats. The milk yield and lactose content increased. The alanine aminotransferase, aspartate transaminase, alkaline phosphatase, pro-inflammatory cytokines, LPS and lactate contents in the plasma significantly decreased, whereas the prolactin and growth hormone levels increased. The hepatic vein glucose content increased. In addition, pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6- phosphatase (G6PC) expression in the liver was significantly up-regulated. In the mammary glands, the levels of glucose transporter type 1, 8, 12 as well as of sodium-glucose cotransporter 1 increased. Cumulative buffering agent treatment increased the blood concentrations of glucose via gluconeogenesis and promoted its synthesis in the liver. This treatment may contribute to the increase of the milk yield and lactose synthesis of lactating goats., L. Li, M. L. He, Y. Liu, Y. S. Zhang., and Seznam literatury
Safranal and crocin are biologically active compounds isolated from Crocus sativus L., commonly known as saffron. Clinical trials confirm that saffron has antidepressant effect, thus being a potential valuable alternative in the treatment of depression. The aim of the present study was to determine, whether systemic administration of safranal and crocin can influence the metabolic activity of CYP3A, CYP2C11, CYP2B, and CYP2A in rat liver microsomes (RLM). The experiments were carried out on male Wistar albino rats intragastrically administered with safranal (4, 20, and 100 mg/kg/day) or with intraperitoneal injections of crocin (4, 20, and 100 mg/kg/day). Our results demonstrate the ability of safranal and crocin to increase the total protein content and to change the metabolic activity of several CYP enzymes assessed as CYP specific hydroxylations of testosterone in RLM. Crocin significantly decreased the metabolic activity of all selected CYP enzymes, while safranal significantly increased the metabolic activity of CYP2B, CYP2C11 and CYP3A enzymes. Therefore, both substances could increase the risk of interactions with co-administered substances metabolized by cytochrome P450 enzymes., G. Dovrtělová, K. Nosková, J. Juřica, M. Turjap, O. Zendulka., and Obsahuje bibliografii