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Sample records for cirrhotic rats depends

  1. Local regulator adrenomedullin contributes to the circulatory disturbance in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Shinya Sakurai; Hideyuki Kojima; Masahito Uemura; Hiroyasu Satoh; Hiroshi Fukui

    2006-01-01

    AIM: To investigate whether adrenomedullin, a potent vasodilator peptide, plays a role in the circulatory disturbance in cirrhosis.METHODS: Cirrhosis was induced in rats by weekly gavage of carbon tetrachloride. Hemodynamic studies were performed in vivo using radioactive microspheres andin vitro using isolated aortic rings.The adrenomedullin concentrations were measured by radioimmunoassay.RESULTS: Acute administration of adrenomedullin to the control rats reduced the systemic arterial pressure along with an increase of serum levels of the stable metabolite of nitric oxide (NOx), in a dose-dependent manner. Chronic infusion of adrenomedullin reduced the vascular resistance and increased the blood flow in the systemic and splanchnic circulation. Intravenous administration of anti-adrenomedullin antibody did not affect any hemodynamic parameters in the cirrhotic rats, whereas this antibody ameliorated the blunted contractile response to phenylephrine, a-adrenergic receptor agonist, in the aortic rings of the cirrhotic rats.The adrenomedullin concentrations in the aorta were higher in the cirrhotic rats than in the controls, and correlated with the mean arterial pressure in the cirrhotic rats. Moreover, adrenomedullin blunted the contractile response to phenylephrine in both of the control aorta and cirrhotic aorta, but not in the presence of NG-nitroL-arginine methyl ester, an NO synthase inhibitor.CONCLUSION: Adrenomedullin overproduced in the vascular wall may contribute to the circulatory disturbance in cirrhosis as a local regulator of the vascular tonus rather than a circulating hormone.

  2. CONCENTRATION AND HEMODYNAMICS PATTERN CHANGES IN CIRRHOTIC RATS

    Institute of Scientific and Technical Information of China (English)

    黄颖秋; 萧树东; 莫剑忠; 张德中

    2000-01-01

    Objective To investigate the effects of hemoglobin (Hb) on serum nitric oxide (NO) concentration and hemodynamics pattern changes in rats with cirrhosis. Methods Cirrhosis model was induced in male SD rats by injection of 60% CCl4 oily solution subcutaneously. Cirrhotic rats were treated with erythropoietin (l00U/kg) injected subcutaneously for 2 weeks. Mean arterial pressure (MAP), cardiac output (CO), cardiac index (CI), splanchnic vascular resistance (SVR), splanchnic blood flow (SBF) and serum NO concentration were determined in erythropoietin - treated, erythropoietin - untreated cirrhotic rats and controls by using 57Co- labelled microsphere technique and a fluorometric assay, respectively. In addition, blood Hb levels were also measured in the 3 groups. Results Untreated cirrhotic rats had significantly lower MAP, SVR, Hb and higher CO, CI, SBF and NO concentration than those of the controls (P<0.01). In treated cirrhotic rats, erythropoietin significantly attenuated the increase of CO, CI, SBF, NO concentration and the decrease of MAP and SVR. In cirrhotic rats,epoetin beta in subcutaneous dose of 100U· kg-1· d-1 induced a markedly increment of blood Hb levels and decrement of NO concentration in comparison with untreated cirrhotic rats (181±11g/L vs 120±15g/L;1.14±0.62μmol/L vs 4.20±1.25μmol/L). Conclusion The endogenous NO may play an important role in the changes of hemodynamics pattern in cirrhosis, and hyperdynamic circulatory status in rats with cirrhosis might be ameliorated by inactivation of overproduced NO by increasing hemoglobin with erythropoietin.

  3. Metformin reduces hepatic resistance and portal pressure in cirrhotic rats.

    Science.gov (United States)

    Tripathi, Dinesh M; Erice, Eva; Lafoz, Erica; García-Calderó, Héctor; Sarin, Shiv K; Bosch, Jaime; Gracia-Sancho, Jordi; García-Pagán, Juan Carlos

    2015-09-01

    Increased hepatic vascular resistance is the primary factor in the development of portal hypertension. Metformin ameliorates vascular cells function in several vascular beds. Our study was aimed at evaluating the effects, and the underlying mechanisms, of metformin on hepatic and systemic hemodynamics in cirrhotic rats and its possible interaction with the effects of propranolol (Prop), the current standard treatment for portal hypertension. CCl4-cirrhotic rats received by gavage metformin 300 mg/kg or its vehicle once a day for 1 wk, before mean arterial pressure (MAP), portal pressure (PP), portal blood flow (PBF), hepatic vascular resistance, and putative molecular/cellular mechanisms were measured. In a subgroup of cirrhotic rats, the hemodynamic response to acute Prop (5 mg/kg iv) was assessed. Effects of metformin ± Prop on PP and MAP were validated in common bile duct ligated-cirrhotic rats. Metformin-treated CCl4-cirrhotic rats had lower PP and hepatic vascular resistance than vehicle-treated rats, without significant changes in MAP or PBF. Metformin caused a significant reduction in liver fibrosis (Sirius red), hepatic stellate cell activation (α-smooth muscle actin, platelet-derived growth factor receptor β polypeptide, transforming growth factor-βR1, and Rho kinase), hepatic inflammation (CD68 and CD163), superoxide (dihydroethidium staining), and nitric oxide scavenging (protein nitrotyrosination). Prop, by decreasing PBF, further reduced PP. Similar findings were observed in common bile duct ligated-cirrhotic rats. Metformin administration reduces PP by decreasing the structural and functional components of the elevated hepatic resistance of cirrhosis. This effect is additive to that of Prop. The potential impact of this pharmacological combination, otherwise commonly used in patients with cirrhosis and diabetes, needs clinical evaluation. PMID:26138461

  4. Quercetin Treatment Ameliorates Systemic Oxidative Stress in Cirrhotic Rats

    Science.gov (United States)

    Vieira, Emanuelle Kerber; Bona, Silvia; Di Naso, Fábio Cangeri; Porawski, Marilene; Tieppo, Juliana; Marroni, Norma Possa

    2011-01-01

    Our aim was to investigate whether the antioxidant quercetin protects against liver injury and ameliorates the systemic oxidative stress in rats with common bile duct ligation. Secondary biliary cirrhosis was induced through 28 days of bile duct obstruction. Animals received quercetin (Q) after 14 days of obstruction. Groups of control (CO) and cirrhotic (CBDL) animals received a daily 50 mg/kg body weight i.p. injection of quercetin (CO + Q; CBDL + Q) or vehicle (CO; CBDL). Quercetin corrected the reduction in superoxide dismutase (SOD), catalase CAT, and glutathione peroxidase GPx activities and prevented the increase of thiobarbituric acid reactive substances (TBARS), aminotransferases, and alkaline phosphatase in cirrhotic animals. Quercetin administration also corrected the reduced total nitrate concentration in the liver and prevented liver fibrosis and necrosis. These effects suggest that quercetin might be a useful agent to preserve liver function and prevent systemic oxidative stress. PMID:21991520

  5. Renal sodium retention in cirrhotic rats depends on glucocorticoid-mediated activation of mineralocorticoid receptor due to decreased renal 11beta-HSD-2 activity

    DEFF Research Database (Denmark)

    Thiesson, Helle; Jensen, Boye L; Bistrup, Claus;

    2007-01-01

    rats with decompensated liver cirrhosis and ascites 7 wk after bile duct ligation (BDL). Renal 11beta-HSD-2 mRNA, protein, and activity were significantly decreased in decompensated rats. The urinary Na(+)/K(+) ratio was reduced by 40%. Renal epithelial sodium channel (ENaC) mRNA and immunostaining......, and reduced ascites formation to the same degree as direct inhibition of MR with K-canrenoate. Total potassium balance was negative in the BDL rats, whereas renal potassium excretion was unchanged. In the distal colon, expression of ENaC was increased in BDL rats. Fecal potassium excretion was increased...... by endogenous glucocorticoids. In addition, the overall potassium loss in the BDL model is due to increased fecal potassium excretion, which is associated with upregulation of ENaC in distal colon....

  6. Chronic nitric oxide synthase inhibition exacerbates renal dysfunction in cirrhotic rats

    DEFF Research Database (Denmark)

    Graebe, Martin; Brond, Lone; Christensen, Sten;

    2004-01-01

    The present study investigated sodium balance and renal tubular function in cirrhotic rats with chronic blockade of the nitric oxide (NO) system. Rats were treated with the nonselective NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) starting on the day of common bile duct ligatio...

  7. Insulin resistance and delayed clearance of peptide hormones in cirrhotic rat liver

    International Nuclear Information System (INIS)

    Clearance of porcine insulin, glucagon, and human growth hormone was measured in intact perfused cirrhotic and normal rat livers. Binding and degradation of 125I-insulin by hepatocytes isolated from cirrhotic and normal livers were also studied. The half-lives (t/sub 1/2/) of immunoreactive insulin and glucagon were 14.0 +/- 3.1 and 9.6 +/- 2.1 min in normal livers and 26.0 +/- 6.1 and 25.0 +/- 7.1 min in cirrhotic livers. Insulin binding and degradation by hepatocytes from control and cirrhotic livers showed no significant differences. Intraportal insulin infusion in perfusion studies suppressed glucagon-stimulated increases in glucose output from control livers but failed to suppress glucose production by cirrhotic livers, suggesting the presence of hepatic insulin resistance in cirrhosis. Impaired clearance of insulin and glucagon by the intact cirrhotic liver and normal binding and degradation of insulin by isolated hepatocytes suggest that factors such as intrahepatic fibrosis and shunting and postbinding defects may be responsible for the impaired hormone clearance and hepatic insulin resistance

  8. Salvianolate inhibits cytokine gene expression in small intestine of cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Dan-Hong Yang; Zai-Yuan Ye; Bo Jin; Xu-Jun He; Qin Zhang; Wei-Ming Zhou; Wen-Juan Xu; Huo-Xiang Lu

    2011-01-01

    AIM: To study the effect of salvianolate on expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 mRNA in small intestine of cirrhotic rats.METHODS: Cirrhosis in rats was induced using CCl4 (0.3 mL/kg).Rats were randomly divided into non-treatment group, low-dose salvianolate (12 mg/kg) treatment group, medium-dose salvianolate (24 mg/kg) treatment group, and high-dose salvianolate (48 mg/kg) treatment group, and treated for 2 wk.Another 10 healthy rats served as a normal control group.Mortality of cirrhotic rats in each group was evaluated after treatment with salvianolate.Serum samples were taken from portal vein for the detection of endotoxin.Morphological changes in tissue samples from the ileocecum were observed under a light microscope.Expression of TNF-α and IL-6 mRNA in the small intestine of rats was analyzed by real-time reverse-transcriptase polymerase chain reaction.RESULTS: The mortality of cirrhotic rats in the nontreatment group was 37.5%.No cirrhotic rat died in the high-dose salvianolate treatment group.The serum endotoxin level was significantly higher in the non-treatment group than in the salvianolate treatment and normal control groups.The intestinal mucosal and villous atrophy, necrosis and shedding of the intestinal mucosal epithelium, observed in the non-treatment group, were reversed in different salvianolate treatment groups.The TNF-α and IL-6 mRNA expression levels in small intestine were significantly lower in different salvianolate treatment groups than in the non-treatment group.CONCLUSION: Salvianolate can reduce the endotoxin level, ameliorate the injury of intestinal mucosa, and inhibit the expression of TNF-α and IL-6 mRNA in small intestine of cirrhotic rats.

  9. Effects of lactulose on intestinal endotoxin and bacterial translocation in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    张顺财; 王唯; 任卫英; 戴茜; 贺伯明; 周康

    2003-01-01

    Objective To investigate the effects of lactulose on intestinal bacterial overgrowth (IBO), bacterial translocation (BT), intestinal transit and permeability in cirrhotic rats. Methods BT in all animals was assessed by bacterial culture of mesenteric lymph node (MLN), liver and spleen, and IBO was assessed by a jejunal bacterial count of the specific organism. Intestinal permeability was determined by the 24-hour urinary 99mTc-diethylenetriaminepentaacetate (99mTc-DTPA) excretion, and intestinal transit was determined by measuring the distribution of 51 Cr in the intestine. Results BT and IBO were found in 48% and 80% of the cirrhotic rats, respectively, while not in the control rats. Cirrhotic rats with IBO had significantly higher levels of intestinal endotoxin higher rates of bacterial translocation, shorter intestinal transit time and higher intestinal permeability than those without IBO. It was also found that BT was closely associated with IBO and injury of the intestinal barrier. Compared with the placebo group, lactulose-treated rats had lower rates of BT and IBO, which was closely associated with increased intestinal transit and improved intestinal permeability by lactulose. Conclusions Our study indicate that endotoxin and bacterial translocation in cirrhotic rats may attribute to IBO and increased intestinal permeability. Lactulose that accelerates intestinal transit and improves intestinal permeability might be helpful in preventing intestinal bacterial and endotoxin translocation.

  10. Effect of L-NAME on nitric oxide and gastrointestinal motility alterations in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Xin Wang; Jie Ding; Kai-Cun Wu; Bo-Rong Pan; Dai-Ming Fan; Yue-Xia Zhong; Zong-You Zhang; Ju Lu; Mei Lan; Ji-Yan Miao; Xue-Gang Guo; Yong-Quan Shi; Yan-Qiu Zhao

    2002-01-01

    AIM: To invsstigare the effect of L-NAME on nitric oxide andgastriubtestubal motility alterations in cirrhotic ratsMETHODS: Rats with cirrhosis induced by carbontetrachloride were randomly divided into two groups, one( n= 13) receiving 0. 5 mg@ kg-1 per clay of NG-nitro-L-argininemethyl ester (L-NAME), a nitric oxide synthase inhibitor,for 10 days, whereas the other group ( n = 13) and control( n = 10) rats were administrated the same volume of 9 g@ L-1saline.Half gastric emptying time and 2 h residual rate weremeasured by SPECT, using 99m Tc-DTPA-labeled bariumsuifate as test meal. Gastrointestinal transition time wasrecorded simultaneously. Serum concentration of nitrcoxide (NO) was determined by the kinetic cadmiunreduction and colorimetric methods. ImmunohistochemicalSABC method was used to observe the expression anddistribution of three types of nitric oxide synthase (NOS)isoforms in the mt gastrointestinal tract. Western blot wasused to detect expression of gastrointestinal NOS isoforms.RESULTS: Half gastric emptying time and trans-gastrointestinal time were significantly prolonged( 124.0 ± 26.4min; 33.7± 8.9min;72.1 ± 15.3 min; P<0.01), (12.4±0.5h; 9.5±0.3 h; 8.2±0.8 h; P<0.01), 2h residual rate wasraised in cirrhotic rots than in controls and cirrhotic ratstreated with L-NAME(54.9± 7.6 % ,13.7 ± 3.2 %, 34.9± 10.3%, P< 0.01). Serum concentration of NO was significantlyincreased in cirrhotic rots than in the other groups (8.20 ± 2.48)μmol@L-1, (5.94± 1.07) μmol@L-1 ,and control (5.66± 1.60) tμmol@L-1, P< 0.01. NOS staining intensities which weremainly located in the gastrointestinal tissues were markedlylower in cirrhotic rats than in the controls and cirrhotic ratsafter treated with L- NAME.CONCLUSION: Gastrointestinal motility was remarkablyinhibited in cirrhotic rats, which could he alleviated by L-NAME. Nitric oxide may play an important role in theinhibition of gastrointestinal motility in cirrhotic rats.

  11. The effect of preconditioning on liver regeneration after hepatic resection in cirrhotic rats

    OpenAIRE

    Min, Seon Ok; Kim, Sung Hoon; Lee, Sang Woo; Cho, Jin A.; Kim, Kyung Sik

    2011-01-01

    Background/Aims Ischemic preconditioning (IP) decreases severity of liver necrosis and has anti-apoptotic effects in previous studies using liver regeneration in normal rats. This study assessed the effect of IP on liver regeneration after hepatic resection in cirrhotic rats. Methods To induce liver cirrhosis, thioacetamide (300 mg/kg) was injected intraperitoneally into Sprague-Dawley rats twice per week for 16 weeks. Animals were divided into four groups: non-clamping (NC), total clamping (...

  12. Vascular endothelial growth factor attenuates hepatic sinusoidal capillarization in thioacetamide-induced cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Hao Xu; Bao-Min Shi; Xiao-Fei Lu; Feng Liang; Xing Jin; Tai-Huang Wu; Jian Xu

    2008-01-01

    AIM: To investigate the effect of vascular endothelial growth factor (VEGF) transfection on hepatic sinusoidal capillarization.MEthODS: Enhanced green fluorescent protein (EGFP)/VEGF transfection was confirmed by immunofluorescencemicroscopy and immunohistoche-mistry both in primaryhepatocytes and in normal liven Cirrhotic rats weregenerated by thioacetamide (TAA) administration andthen divided into a treatment group, which receivedinjections of 400 μg of plasmid DNA encoding an EGFP-VEGF fusion protein, and a blank group, which receivedan equal amount of normal saline through the portalvein. The portal vein pressure was measured in the normal and cirrhotic state, in treated and blank groups.The average number of fenestrae per hepatic sinusoidwas determined using transmission electron microscopy(TEM), while the relative abundance of VEGF transcriptswas examined by Gene array.RESULTS: Green fluorescent protein was observed in the cytoplasms of liver cells under immunofluorescence microscopy 24 h after transfection with EGFP/VEGFplasmid in vitro. Staining with polyclonal antibodies against VEGF illustrated that hepatocytes expressed immunodetectable VEGF both in vitro and in vitro. There were significant differences in the number of fenestrae and portal vein pressures between normal and cirrhotic rats (7.40±1.71 vs 2.30± 2.26 and 9.32± 0.85 cmH2Ovs 27.92± 0.90 cmH2O1, P < 0.02), between cirrhotic and treated rats (2.30 + 1.16 cmH2O vs 4.60± 1.65 and 17.92± 0.90 cmH2O vs 15.52±0.93 cmH20, P < 0.05)and between the treatment group and the blank group (4.60±1.65 cmH20 vs 2.10 ± 1.10 cmH20 and 25.52 +0.93 cmH20 vs 17.26 ± 1.80 cmH20, P < 0.05). Gene-array analysis revealed that the relative abundance oftranscripts of VEGF family members decreased in the cirrhotic state and increased after transfection. CONCLUSION: Injection of a plasmid encoding VEGFthrough the portal vein is an effective method toinduce the formation of fenestrae and decrease portalvein

  13. Endothelial nitric oxide synthase regulation is altered in pancreas from cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Jean-Louis Frossard; Rafael Quadri; Antoine Hadengue; Philippe Morel; Catherine M Pastor

    2006-01-01

    AIM: To determine whether biliary cirrhosis could induce pancreatic dysfunction such as modifications in endothelial nitric oxide synthase(eNOS) expression and whether the regulation of eNOS could be altered by the regulatory proteins caveolin and heat shock protein 90 (Hsp90),as well as by the modifications of calmodulin binding to eNOS.METHODS: Immunoprecipitations and Western blotting analysis were performed in pancreas isolated from sham and cirrhotic rats.RESULTS: Pancreatic injury was minor in cirrhotic rats but eNOS expression importantly decreased with the length (and the severity) of the disease. Because coimmunoprecipitation of eNOS with both Hsp90 and caveolin similarly decreased in cirrhotic rats, eNOS activity was not modified by this mechanism. In contrast,cirrhosis decreased the calmodulin binding to eNOS with a concomitant decrease in eNOS activity.CONCLUSION: In biliary cirrhosis, pancreatic injury is minor but the pancreatic nitric oxide (NO) production is significantly decreased by two mechanisms: a decreased expression of the enzyme and a decreased binding of calmodulin to eNOS.

  14. In vivo gene transfer of endothelial nitric oxide synthase decreases portal pressure in anaesthetised carbon tetrachloride cirrhotic rats

    Science.gov (United States)

    Van de Casteele, M; Omasta, A; Janssens, S; Roskams, T; Desmet, V; Nevens, F; Fevery, J

    2002-01-01

    Background: Portal hypertension in cirrhosis results from enhanced intrahepatic resistance to an augmented inflow. The former is partly due to an imbalance between intrahepatic vasoconstriction and vasodilatation. Enhanced endothelin-1 and decreased activity of hepatic constitutive endothelial nitric oxide synthase (NOS 3) was reported in carbon tetrachloride (CCl4) cirrhotic rat liver. Aims: To study whether an increase in hepatic NOS 3 could be obtained in the CCl4 cirrhotic rat liver by in vivo cDNA transfer and to investigate a possible effect on portal pressure. Methods: Hepatic NOS 3 immunohistochemistry and western blotting were used to measure the amount of NOS 3 protein. Recombinant adenovirus, carrying cDNA encoding human NOS 3, was injected into the portal vein of CCl4 cirrhotic rats. Cirrhotic controls received carrier buffer, naked adenovirus, or adenovirus carrying the lac Z gene. Results: NOS 3 immunoreactivity and amount of protein (western blotting) were significantly decreased in CCl4 cirrhotic livers. Following cDNA transfer, NOS 3 expression and the amount of protein were partially restored. Portal pressure was 11.4 (1.6) mm Hg in untreated cirrhotic (n=9) and 11.8 (0.6) in lac Z transfected (n=4) cirrhotic rats but was reduced to 7.8 (1.0) mm Hg (n=9) five days after NOS 3 cDNA transfer. No changes were observed in systemic haemodynamics, in liver tests or urinary nitrates, or in NOS 3 expression in lung or kidney, indicating a highly selective transfer. Conclusions: NOS 3 cDNA transfer to cirrhotic rat liver is feasible and the increase in hepatic NOS 3 leads to a marked decrease in portal hypertension without systemic effects. These data indicate a major haemodynamic role of intrahepatic NOS 3 in the pathogenesis of portal hypertension in CCl4 cirrhosis. PMID:12171971

  15. Activity of glycogen synthase and glycogen phosphorylase in normal and cirrhotic rat liver during glycogen synthesis from glucose or fructose.

    Science.gov (United States)

    Bezborodkina, Natalia N; Chestnova, Anna Yu; Okovity, Sergey V; Kudryavtsev, Boris N

    2014-03-01

    Cirrhotic patients often demonstrate glucose intolerance, one of the possible causes being a decreased glycogen-synthesizing capacity of the liver. At the same time, information about the rates of glycogen synthesis in the cirrhotic liver is scanty and contradictory. We studied the dynamics of glycogen accumulation and the activity of glycogen synthase (GS) and glycogen phosphorylase (GP) in the course of 120min after per os administration of glucose or fructose to fasted rats with CCl4-cirrhosis or fasted normal rats. Blood serum and liver pieces were sampled for examinations. In the normal rat liver administration of glucose/fructose initiated a fast accumulation of glycogen, while in the cirrhotic liver glycogen was accumulated with a 20min delay and at a lower rate. In the normal liver GS activity rose sharply and GPa activity dropped in the beginning of glycogen synthesis, but 60min later a high synthesis rate was sustained at the background of a high GS and GPa activity. Contrariwise, in the cirrhotic liver glycogen was accumulated at the background of a decreased GS activity and a low GPa activity. Refeeding with fructose resulted in a faster increase in the GS activity in both the normal and the cirrhotic liver than refeeding with glucose. To conclude, the rate of glycogen synthesis in the cirrhotic liver is lower than in the normal one, the difference being probably associated with a low GS activity.

  16. Effect of portal vein ligation on tumor growth and liver regeneration in rat cirrhotic liver lobes

    OpenAIRE

    Xu, Rui; YUAN, YU-FENG; Ayav, Ahmet; JIANG, CHONG-QING; BRESLER, LAURENT; Liu, Zhi-Su; Tran, Nguyen

    2014-01-01

    The aim of the present study was to investigate the effect of portal vein ligation (PVL) on the tumor growth rate and liver regeneration in rat cirrhotic liver lobes. A total of 45 male Wistar rats were randomly divided into PVL, hepatic tumor (HT) and HT + PVL groups (n=15 per group). Liver regeneration and tumor growth in ligated and non-ligated lobes were evaluated prior to and following PVL. In addition, serum alanine transaminase, total bilirubin levels and liver tissue samples were eval...

  17. Effect of early propranolol administration on portal hypertensive gastropathy in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Savas Rafailidis; Charalampos Demertzidis; Konstantinos Ballas; Michail Alatsakis; Nikolaos Symeonidis; Theodoros Pavlidis; Kyriakos Psarras; Valentini Tzioufa-Asimakopoulou; Athanassios Sakadamis

    2009-01-01

    AIM: To investigate any protective effect of early propranolol administration in the development of portal hypertensive gastropathy in cirrhotic rats. METHODS: For the development of liver cirrhosis and portal hypertensive gastropathy, 60 rats underwent ligation of the left adrenal vein and complete devascularization of the left renal vein, followed by phenobarbital and carbon tetrachloride (CCl4) administration. After two weeks of CCl4 administration, the rats were randomly separated into two groups. In group A, propranolol was continuously administered intragastrically throughout the study, whereas in group B normal saline (placebo) was administered instead. Hemodynamic studies and vascular morphometric analysis of gastric sections were performed after complete induction of cirrhosis. RESULTS: Vascular morphometric studies showed higher numbers of vessels in all mucosal layers in the control group. Statistical analysis revealed a significantly higher total vascular surface in the control group compared to the propranolol group, but with no statistically significant difference between the mean vascular surfaces between the groups. Our study clearly shows that the increased mucosal blood flow is manifested by a marked increase of vessel count. CONCLUSION: Early propranolol's administration in portal hypertensive cirrhotic rats seems to prevent intense gastric vascular congestion that characterizes portal hypertensive gastropathy.

  18. Rifaximin, but not growth factor 1, reduces brain edema in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Gemma (ò)dena; Mireia Miquel; Anna Serafín; Amparo Galan; Rosa Morillas; Ramon Planas; Ramon Bartolí

    2012-01-01

    AIM:To compare rifaximin and insulin-like growth factor (IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion.METHODS:Rats with CCl4-induced cirrhosis with ascites plus portal vein occlusion and controls were randomized into six groups:Cirrhosis; Cirrhosis + IGF-1;Cirrhosis + rifaximin; Controls; Controls + IGF-1; and Controls + rifaximin.An oral glutamine-challenge test was performed,and plasma and cerebral ammonia,glucose,bilirubin,transaminases,endotoxemia,brain water content and ileocecal cultures were measured and liver histology was assessed.RESULTS:Rifaximin treatment significantly reduced bacterial overgrowth and endotoxemia compared with cirrhosis groups,and improved some liver function parameters (bilirubin,alanine aminotransferase and aspartate aminotransferase).These effects were associated with a significant reduction in cerebral water content.Blood and cerebral ammonia levels,and area-underthe-curve values for oral glutamine-challenge tests were similar in rifaximin-treated cirrhotic rats and control group animals.By contrast,IGF-1 administration failed to improve most alterations observed in cirrhosis.CONCLUSION:By reducing gut bacterial overgrowth,only rifaximin was capable of normalizing plasma and brain ammonia and thereby abolishing low-grade brain edema,alterations associated with hepatic encephalopathy.

  19. Tetrandrine Ameliorates Cirrhosis and Portal Hypertension by Inhibiting Nitric Oxide in Cirrhotic Rats

    Institute of Scientific and Technical Information of China (English)

    王海; 陈孝平

    2004-01-01

    To examine the role and effect of nitric oxide synthase type Ⅱ (NOSⅡ) in cirrhotic rats,expression of NOSⅡ mRNA was detected by real time RT-PCR. The enzymatic activity of nitric oxide synthase and the circulating levels of NO, systemic and portal hemodynamics and quantification of cirrhosis were measured. Chinese traditional medicine was used to treat cirrhotic rats and the effect of NO was evaluated. Double-blind method was used in experiment. Our results showed the concentration of NO and the enzymatic activity of NOS increased markedly at all stages of cirrhosis and iNOSmRNA was strongly expressed. Meanwhile, the portal-venous-pressure (PVP) and portal-venous-flow (PVF) were significantly increased. NO, NOS and iNOSmRNA were positively correlated to the degree of hepatic fibrosis. Tetrandrine significantly inhibited NO production and the expression of iNOSmRNA. Our results suggested that increased hepatic expression of NOS Ⅱ is one of the important factors causing cirrhosis and portal hypertension. Tetrandrine can significantly ameliorate cirrhosis and portal hypertension.

  20. Celecoxib and octreotide synergistically ameliorate portal hypertension via inhibition of angiogenesis in cirrhotic rats.

    Science.gov (United States)

    Gao, Jin-Hang; Wen, Shi-Lei; Feng, Shi; Yang, Wen-Juan; Lu, Yao-Yao; Tong, Huan; Liu, Rui; Tang, Shi-Hang; Huang, Zhi-Yin; Tang, Ying-Mei; Yang, Jin-Hui; Xie, Hui-Qi; Tang, Cheng-Wei

    2016-10-01

    Abnormal angiogenesis is critical for portal hypertension in cirrhosis. Except for etiological treatment, no efficient medication or regime has been explored to treat the early stage of cirrhosis when angiogenesis is initiated or overwhelming. In this study, we explored an anti-angiogenesis effort through non-cytotoxic drugs octreotide and celecoxib to treat early stage of cirrhotic portal hypertension in an animal model. Peritoneal injection of thioacetamide (TAA) was employed to induce liver cirrhosis in rats. A combination treatment of celecoxib and octreotide was found to relieve liver fibrosis, portal venous pressure, micro-hepatic arterioportal fistulas, intrahepatic and splanchnic angiogenesis. Celecoxib and octreotide exerted their anti-angiogenesis effect via an axis of cyclooxygenase-2/prostaglandin E2/EP-2/somatostatin receptor-2, which consequently down-regulated phosphorylation of extracellular signal-regulated kinase (p-ERK)-hypoxia-inducible factor-1α (HIF-1α)-vascular endothelial growth factor (VEGF) integrated signaling pathways. In conclusions, combination of celecoxib and octreotide synergistically ameliorated liver fibrosis and portal hypertension of the cirrhotic rats induced by TAA via the inhibition of intrahepatic and extrahepatic angiogenesis. The potential mechanisms behind the regimen may due to the inactivation of p-ERK-HIF-1α-VEGF signaling pathway. PMID:27380212

  1. Increased hepatic expression of nitric oxide synthase type Ⅱ in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Hai Wang; Xiao-Ping Chen; Fa-Zu Qiu

    2004-01-01

    AIM: To determine the role and effect of nitric oxide synthase type Ⅱ (NOSⅡ) in cirrhotic rats.METHODS: Expression of NOSⅡ mRNA was detected by real time RT-PCR. The activity of nitric oxide synthase and serum levels of NO, systemic and portal hemodynamics and degrees of cirrhosis were measured with high sensitive methods. Chinese traditional medicine tetrandrine was used to treat cirrhotic rats and to evaluate the function of NO.Double-blind method was applied during the experiment.RESULTS: The concentration of NO and the activity of NOS were increased markedly at all stages of cirrhosis, and iNOSmRNA was greatly expressed. Meanwhile the portalvenous-pressure (PVP), and portal-venous-flow (PVF) were significantly increased. NO, NOS and iNOSmRNA were positively correlated to the quantity of hepatic fibrosis.Tetrandrine significantly inhibited NO production and the expression of iNOSmRNA.CONCLUSION: Increased hepatic expression of NOSⅡ is one of the important causes of hepatic cirrhosis and portal hypertension.

  2. Xiayuxue decoction reduces renal injury by promoting macrophage apoptosis in hepatic cirrhotic rats.

    Science.gov (United States)

    Liu, C; Cai, J; Cheng, Z; Dai, X; Tao, L; Zhang, J; Xue, D

    2015-01-01

    Renal pathological changes in cirrhotic rat have not been extensively reported. The aim of this study was to investigate whether Xiayuxue decoction (XYXD) could attenuate renal injury induced by bile duct ligation (BDL), with special focus on the mechanisms promoting renal macrophage apoptosis. The rats were treated with BDL for 5 weeks and administered 0.36 g/kg XYXD intragastrically from day 1 of initiating BDL. Renal tissue was monitored by hematoxylin-eosin and Sirius red staining. Macrophage infiltration and proinflammatory cytokines such as tumor necrosis factor and chemokine ligand 2 were detected by quantitative polymerase chain reaction. Macrophage apoptosis was detected by double immunofluorescence staining. Blood urea nitrogen, creatinine, and glomerulus diameter increased significantly after a 5-week BDL treatment in XYXD (BDL-XYXD) rats. CD68 and pro-inflammatory cytokine mRNA increased in the kidneys of control (BDL-water) rats. Fluorescence microscopy analysis showed that XYXD promoted apoptosis in renal CD68+ macrophages. Collogen1 (Col 1), pro-fibrogenic cytokines, and α-smooth muscle actin in kidneys of BDL-water rats increased significantly compared to the sham group. XYXD inhibited Col 1 and pro-fibrotic factors in BDL-XYXD rats. Our results demonstrated that XYXD significantly reduced renal injury by, at least in part, promoting macrophage apoptosis in rats with damaged renal histopathology due to BDL-induced cirrhosis. PMID:26400305

  3. The role of vasoactive substances in hyperhemodynamics after orthotopic liver transplantation in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    曹晖; 吴志勇; 张效杰; 张海婴; 陈治平; 邝耀麟

    2003-01-01

    Objective To evaluate the role of endogenous vasoactive substances in hyperdynamic circulation after orthotopic liver transplantation (OLT) in cirrhotic rats.Methods Male SD rats were randomly divided into 4 groups: normal controls (NL, n=10), rats with intrahepatic portal hypertension (IHPH, n=10), normal rats with OLT (NL-OLT, n=9), and IHPH rats with OLT (IHPH-OLT, n=16). IHPH-OLT rats were divided into 2 subgroups: Group A (3 days after OLT, n=9) and Group B (7 days after OLT, n=7). IHPH was induced by injection of CCI4 and OLT was performed using cuffs for the anastomosis of suprahepatic inferior vena cava, infrahepatic vena cava and portal vein. Radioactive microsphere method was used for hemodynamic study. The concentrations of plasma glucagon (Glu), nitric oxide (NO), prostaglandin (PGI2), thromboxaneA2 (TXA2) and endothelin (ET) were measured by radioimmunoassay. Results No significant difference in hemodynamic changes was observed between NL-OLT and NL rats, except for mean arterial blood pressure. No significant changes in NO and PGI2 were seen between NL-OLT and NL rats. Glu, ET and TXA2 were significantly elevated in NL-OLT rats compared with NL rats (PIHPH-OLT A>IHPH-OLT B rats. The level of plasma PGI2 in IHPH rats was significantly elevated compared with NL rats, while PGI2 in IHPH-OLT A and B rats was found to be lower than in IHPH rats (P<0.05). There was no obvious difference in PGI2 between IHPH-OLT B and NL rats. Vasoconstrictors including ET and TXA2 were found elevated in IHPH-OLT rats. Conclusions OLT does not induce postoperative hyperhemodynamics per se. Vasodilators including NO and Glu, especially NO, play an important role in the hyperhemodynamics of IHPH and IHPH-OLT rats. The results of the present study demonstrate that the persistence of systemic and splanchnic hyperkinetic circulation in the early stages after OLT may result from those non-eliminated factors that caused hyperhemodynamics in liver cirrhosis patients with portal

  4. Changes in systemic and splanchnic hemodynamics after orthotopic liver transplantation in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To investigate early changes in systemic and splanchnic hemodynamics after orthotopic liver transplantation (OLT) in normal and cirrhotic rats. Methods Male Sprague-Dawley rats were divided into 4 groups:normal controls (NL,n=10),intrahepatic portal hypertension (IHPH, n=10) induced by injection of CCl4, normal rats with OLT (NL-OLT,n=9) and IHPH rats with OLT (IHPH-OLT,n=16). IHPH-OLT rots were divided into 2 subgroups: 3 days (Group A, n=9) and 7 days (Group B, n=7) after OLT. OLT was pedormed in rats using cuffs for the anastomosis of the suprahepatic inferior vena cava,infrahepatic vena cava and portal vein. Two weeks after production of IHPH rots, 7 days after NL-OLT rats, 3 days and 7 days after IHPH-OLT rats, radicective microspheres were used in a hemodynamic study. Results There were no significant differences in hemodynamic changes between NL-OLT and NL rets, except mean arterial blood pressure (MAP).The characteristies of systemic and splanchnic hyperdynamic circulatory slate,including increased cardiac output and splanchnic blood flow, decreased mean acterial blood pressure, total peripheral vascular resistance and splanchnic vascular resistance were ibserved in IHPH, IHPH-OLT A, and IHPH-OLT B rats,The magnitude of hyperhemodynamics was in the order of IHPH>IHPH-OLT A>IHPH-OLT B rats. Moreover, the derangement of splanchnic hyper hemodynamice was more significant than that of systemic hyperhemodynamics. Conclusioos The present study demonstrates that the persistence of early systemic and splanchnic hyperkinetic circulation after OLT may be the consequence of factors which maintain hyperhemo dynamics in liver cirrhosis, where portal hypertension is not completely eliminated. Hyperhemodynamics is not induced by OLT per se.

  5. Effects of nitric oxide synthesis inhibitor in long-term treatment onhyperdynamic circulatory state in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Ying Qiu Huang; Shu Dong Xiao; Jian Zhong Mo; De Zhong Zhang

    2000-01-01

    AIM To investigate the effects of low dosage of nitric oxide synthesis (NOS) inhibitor NG-nitro-L-argininemethyl ester (L-NAME) in long-term treatment on hyperdynamic circulatory state in rats with cirrhosis.METHODS Cirrhosis model was induced in male SD rats by injection of 60% CC14 oily solutionsubcutaneously. Cirrhotic rats were treated with L-NAME (0.5 mg·kg-1·d-1) by gavage for two weeks. Meanarterial pressure (MAP), cardiac output (CO), cardiac index (CI), splanchnic vascular resistance (SVR),splanchnic blood flow (SBF) and serum NO levels were determinded in L-NAME-treated, L-NAME-untreated cirrhotic rats and controls by using 57Co-Labled microsphere technique and a fluorometric assay,respectively.RESULTS Untreated cirrhotic rats had significantly lower MAP, SVR and higher PP, CO, CI, SBF andNO concentration than controls ( 14.42±0,47 kPa vs 17.05±0.34 kPa, 2.974±0.186 kPa·mL-1·min-1 vs4.234±0.118 kPa·mL-1·min-1, 1.665±0.067 kPa vs 1.123±0.096 kPa, 189.99±9.26 mL/min vs 135.5±3.55 mL/min, 55.89±1.82 mL-1·min-1·100g-1 BW vs 39.68±1.64 mL-1·min-1·100g-1 BW, 4.60±1.25μmol/L vs 0.53±0.26 μmol/L, P<0.01, respectively). In treated cirrhotic rats, L-NAME significantlyattenuated the increase of CO, CI, SBF, NO concentration and the decrease of MAP and SVR. In treatedcirrhotic rats, L-NAME induced a marked decrement of NO concentration than untreated cirrhotic rats(1.471 ±0.907 μmol/L vs 4.204±1.253 μmol/L, P<0.01).CONCLUSION The endogenous NO may play an important role in the changes of hemodynamics pattern incirrhosis,and hyperdynamic circulatory state in rats with cirrhosis can be ameliorated by long-term low doseL-NAME treatment.

  6. Effect of salvianolate on intestinal epithelium tight junction protein zonula occludens protein 1 in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Dan-Hong Yang; Zai-Yuan Ye; Yuan-Jun Xie; Xu-Jun He; Wen-Juan Xu; Wei-Ming Zhou

    2012-01-01

    AIM:To study the effect of salvianolate on tight junctions (TJs) and zonula occludens protein 1 (ZO-1) in small intestinal mucosa of cirrhotic rats.METHODS:Cirrhosis was induced using carbon tetrachloride.Rats were randomly divided into the untreated group,low-dose salvianolate (12 mg/kg) treatment group,medium-dose salvianolate (24 mg/kg) treatment group,and high-dose salvianolate (48 mg/kg) treatment group,and were treated for 2 wk.Another 10 healthy rats served as the normal control group.Histological changes in liver tissue samples were observed under a light microscope.We evaluated morphologic indices of ileal mucosa including intestinal villi width and thickness of mucosa and intestinal wall using a pathological image analysis system.Ultrastructural changes in small intestinal mucosa were investigated in the five groups using transmission electron microscopy.The changes in ZO-1 expression,a tight junction protein,were analyzed by immunocytochemistry.The staining index was calculated as the product of the staining intensity score and the proportion of positive cells.RESULTS:In the untreated group,hepatocytes showed a disordered arrangement,fatty degeneration was extensive,swelling was obvious,and disorganized lobules were divided by collagen fibers in hepatic tissue,which were partly improved in the salvianolate treated groups.In the untreated group,abundant lymphocytes infiltrated the fibrous tissue with proliferation of bile ducts,and collagen fibers gradually decreased and damaged hepatic lobules were partly repaired following salvianolate treatment.Compared with the untreated group,no differences in intestinal villi width between the five groups were observed.The villi height as well as mucosa and intestinal wall thickness gradually thickened with salvianolate treatment and were significantly shorter in the untreated group compared with those in the salvianolate treatment groups and normal group (P < 0.01).The number of microvilli decreased and showed

  7. Cirrhotic cardiomyopathy

    DEFF Research Database (Denmark)

    Wiese, Signe; Hove, Jens D; Bendtsen, Flemming;

    2014-01-01

    biomarkers could improve the diagnostic assessm+ent. Cirrhotic cardiomyopathy contributes to various complications in cirrhosis, especially as an important factor in the development of hepatic nephropathy. Additionally, cirrhotic cardiomyopathy seems to be associated with the development of heart failure...... in relation to invasive procedures such as shunt insertion and liver transplantation. Current pharmacological treatment is nonspecific and directed towards left ventricular failure, and liver transplantation is currently the only proven treatment with specific effect on cirrhotic cardiomyopathy....

  8. Effect of liver ischemic preconditioning in cirrhotic rats submitted to hepatic ischemia/reperfusion injury Efeito do pré-condicionamento isquêmico hepático submetidos a lesão de isquemia/reperfusão do fígado

    OpenAIRE

    Eduardo Garcia Pacheco; Maria Cecília Jordani Gomes; Gustavo Ribeiro Rodrigues; Walter Campos; Rafael Kemp; Orlando de Castro e Silva

    2006-01-01

    PURPOSE: The main aim of this study was to determine the influence of ischemic preconditioning (IPC) on rat liver cirrhosis. METHODS: Cirrhosis was induced in Wistar rats by occlusion of the hepatic duct. The animals were divided into four groups of six animals each: non-cirrhotic group (simulated operation only), cirrhotic control group (simulated operation in cirrhotic rats), I/R group (40-minute ischemia without IPC), and IPC group (cirrhotic rats with ischemia, previously submitted to IPC...

  9. Cirrhotic cardiomyopathy.

    Science.gov (United States)

    Milani, A; Zaccaria, R; Bombardieri, G; Gasbarrini, A; Pola, P

    2007-06-01

    Decompensated liver cirrhosis is characterized by a peripheral vasodilation with a low-resistance hyperdynamic circulation. The sustained increase of cardiac work load associated with such a condition may result in an inconstant and often subclinical series of heart abnormalities, constituting a new clinical entity known as "cirrhotic cardiomyopathy". Cirrhotic cardiomyopathy is variably associated with baseline increase in cardiac output, defective myocardial contractility and lowered systo-diastolic response to inotropic and chronotropic stimuli, down-regulated beta-adrenergic function, slight histo-morphological changes, and impaired electric "recovery" ability of ventricular myocardium. Cirrhotic cardiomyopathy is usually clinically latent or mild, likely because the peripheral vasodilation significantly reduces the left ventricle after-load, thus actually "auto-treating" the patient and masking any severe manifestation of heart failure. In cirrhotic patients, the presence of cirrhotic cardiomyopathy may become unmasked and clinically evident by certain treatment interventions that increase the effective blood volume and cardiac pre-load, including surgical or transjugular intrahepatic porto-systemic shunts, peritoneo-venous shunts (LeVeen) and orthotopic liver transplantation. Under these circumstances, an often transient overt congestive heart failure may develop, with increased cardiac output as well as right atrial, pulmonary artery and capillary wedge pressures. PMID:17383244

  10. Celecoxib ameliorates portal hypertension of the cirrhotic rats through the dual inhibitory effects on the intrahepatic fibrosis and angiogenesis.

    Directory of Open Access Journals (Sweden)

    Jin-Hang Gao

    Full Text Available BACKGROUND: Increased intra-hepatic resistance to portal blood flow is the primary factor leading to portal hypertension in cirrhosis. Up-regulated expression of cyclooxygenase-2 (COX-2 in the cirrhotic liver might be a potential target to ameliorate portal hypertension. OBJECTIVE: To verify the effect of celecoxib, a selective inhibitor of COX-2, on portal hypertension and the mechanisms behind it. METHODS: Cirrhotic liver model of rat was established by peritoneal injection of thiacetamide (TAA. 36 rats were randomly assigned to control, TAA and TAA+celecoxib groups. Portal pressures were measured by introduction of catheters into portal vein. Hepatic fibrosis was assessed by the visible hepatic fibrotic areas and mRNAs for collagen III and α-SMA. The neovasculature was determined by hepatic vascular areas, vascular casts and CD31 expression. Expressions of COX-2, vascular endothelial growth factor (VEGF, VEGF receptor-2 (VEGFR-2 and related signal molecules were quantitated. RESULTS: Compared with TAA group, the portal pressure in TAA+celecoxib group was significantly decreased by 17.8%, p<0.01. Celecoxib treatment greatly reduced the tortuous hepatic portal venules. The data of fibrotic areas, CD31expression, mRNA levels of α-SMA and collagen III in TAA+celecoxib group were much lower than those in TAA group, p<0.01. Furthermore, the up-regulation of hepatic mRNA and protein levels of VEGF, VEGFR-2 and COX-2 induced by TAA was significantly inhibited after celecoxib treatment. The expressions of prostaglandin E2 (PGE2, phosphorylated extracellular signal-regulated kinase (p-ERK, hypoxia-inducible factor-1α (HIF-1α, and c-fos were also down-regulated after celecoxib treatment. CONCLUSIONS: Long term administration of celecoxib can efficiently ameliorate portal hypertension in TAA rat model by its dual inhibitory effects on the intrahepatic fibrosis and angiogenesis. The anti-angiogenesis effect afforded by celecoxib may attribute to its

  11. Blueberry treatment attenuated cirrhotic and preneoplastic lesions and oxidative stress in the liver of diethylnitrosamine-treated rats.

    Science.gov (United States)

    Bingül, İlknur; Başaran-Küçükgergin, Canan; Aydın, A Fatih; Soluk-Tekkeşin, Merva; Olgaç, Vakur; Doğru-Abbasoğlu, Semra; Uysal, Müjdat

    2016-09-01

    Diethylnitrosamine (DEN)-induced liver cancer normally develops in stages that progress from cirrhosis and carcinoma. Increased oxidative stress is suggested to play a role in DEN-induced carcinogenicity. Blueberries (BB) contain high antioxidant capacity. We investigated the effect of BB supplementation on development of DEN-induced cirrhosis and neoplastic lesions in the liver. Rats were injected with DEN (200 mg/kg; i.p.) three times with an interval of 15 days at 4, 6, and 8 weeks and sacrificed 8 weeks after the last DEN injection. They were also fed on 8% BB (w/w) containing chow for 16 weeks. Hepatic damage markers in serum were determined together with hepatic histopathological examinations. Hydroxyproline (HYP), malondialdehyde (MDA), diene conjugate (DC), protein carbonyl (PC), and glutathione (GSH) levels, and CuZn-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, and their mRNA expressions were measured. Protein and mRNA expressions of glutathione transferase-pi (GST-pi) were evaluated as a marker of preneoplastic lesions. BB supplementation decreased hepatic damage markers in serum and hepatic MDA, DC, and PC levels, but SOD, CAT, and GSH-Px activities and their mRNA expressions remained unchanged in DEN-treated rats. BB attenuated cirrhotic changes and decreased hepatic HYP levels and GST-pi expressions. Our results indicate that BB is effective in decreasing development of DEN-induced hepatic cirrhosis and preneoplastic lesions by acting as an antioxidant (radical scavenger) itself without affecting activities and mRNA expressions of antioxidant enzymes. PMID:26684621

  12. Intestinal endotoxemia plays a central role in development of hepatopulmonary syndrome in a cirrhotic rat model induced by multiple pathogenic factors

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To characterize the correlation between severity of hepatopulmonary syndrome (HPS) and degree of hepatic dysfunction, and to explore how intestinal endotoxemia (IETM) affects the development of HPS in cirrhotic rats.METHODS: Male Wister rats were fed with a diet containing maize flour, lard, cholesterol, and alcohol and injected subcutaneously with CCl4 oil solution every two days for 8 wk to induce typical cirrhosis and development of HPS. The animals were also given a nitric oxide (NO) production inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME) intraperitoneally, and an iNOS inhibitor, aminoguanidine hydrochloride (AG) via gavage daily from the end of the 4th wk to the end of the 6th or 8th wk, or a HO-1 inhibitor, zinc protoporphyrin (ZnPP) intraperitoneally 12 h prior to killing. Blood, liver and lung tissues were sampled.RESULTS: Histological deterioration of the lung paralleled to that of the liver in the cirrhotic rats. The number of pulmonary capillaries was progressively increased from 6.1±1.1 (count/filed) at the 4th wk to 14.5±2.4 (count/filed) at the 8th wk in the cirrhotic rats. Increased pulmonary capillaries were associated with increased blood levels of lipopolysaccharide (LPS) (0.31±0.08 EU/mL vs control 0.09±0.03 EU/mL),alanine transferase (ALT, 219.1±17.4 U/L vs control 5.9±2.2 U/L) and portal vein pressure. Compared with normal control animals, the number of total cells in bronchoalveolar lavage fluid (BALF) of the cirrhotic rats at the 8th wk was not changed, but the number of macrophages and the ratio of macrophages to total cells were increased by nearly 2-fold, protein expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) started to increase significantly at the 4th wk, and reached its peak at the 8th wk in the lung of cirrhotic rats. The increase of iNOS expression appeared to be quicker than that of eNOS.NO2-/NO3-was also increased, which was correlated to the increase of iNOS (r

  13. Child-Pugh classification dependent alterations in serum leptin levels among cirrhotic patients: a case controlled study

    Directory of Open Access Journals (Sweden)

    Zeyrek Fadile

    2004-09-01

    Full Text Available Abstract Background As anorexia and hypermetabolism are common in cirrhosis, leptin levels may be increased in this disease. In this study, we investigated the relation between the severity of disease and serum leptin levels in post-hepatitis cirrhosis and the role of body composition, gender and viral aetiology of cirrhosis in this association. Methods Thirty-five cases with post-hepatitis cirrhosis and 15 healthy controls were enrolled in this study. Body composition including body mass index, body fat percentage and body fat mass were determined. Serum leptin levels were assayed. Results Leptin levels were significantly higher among cirrhotic patients independent of sex compared to controls (p = 0.001. Female patients in both groups have had higher leptin levels than males (in cirrhotics p = 0.029, in controls p = 0.02. Cirrhotic patients in each of A, B and C subgroups according to the Child- Pugh classification revealed significantly different levels compared to controls (p = 0.046, p = 0.004, p = 0.0001, respectively. Male cirrhotics in Child-Pugh Class B and C subgroups had significantly higher leptin levels compared to male controls (p = 0.006, p = 0.008. On the other hand, female patients only in Child Pugh class C subgroup have had higher levels of serum leptin compared to controls (p = 0.022. Child-Pugh classification has been found to be the sole discriminator in determination of leptin levels in cirrhotics by linear regression (beta: 0.435 p = 0.015. Conclusion Serum leptin levels increase in advanced liver disease independently of gender, body composition in posthepatitic cirrhosis. The increase is more abundant among patients that belong to C subgroup according to the Child- Pugh classification.

  14. Uso de quercetina a longo prazo em ratos cirróticos The long term use of quercetin in cirrhotic rats

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    Aline Miltersteiner

    2003-06-01

    Full Text Available OBJETIVO: Avaliar o uso a longo prazo do flavonóide quercetina em ratos cirróticos por ligadura de ducto biliar comum (LDB. MÉTODOS: Foram utilizados 32 ratos machos Wistar, sendo submetidos à LDB ou simulação, e distribuídos em 4 grupos: 1 controle, 2 cirróticos, 3 cirróticos tratados com quercetina 50mg/kg, intraperitonealmente, desde o segundo dia após o procedimento cirúrgico; e 4 cirróticos tratados após o décimo quarto dia do procedimento cirúrgico. Analisou-se a função hepática por meio de testes bioquímicos (BT e BD e atividade enzimática (ALT, AST, FA e GGT. Na análise anatomopatológica, utilizou-se a coloração de Hematoxilina & Eosina (H&E e de Picrosírius para fibrose. A análise estatística para avaliação de sobrevivência foi realizada pelo teste Kaplan-Meier. RESULTADOS: Os resultados de sobrevivência dos oito animais de cada grupo foram: Grupo 1 = 200 dias de sobrevivência; Grupo 2 = 46 dias; Grupo 3 = 71 dias; e o Grupo 4 = 90 dias. Nos animais com ligadura de ducto biliar comum houve aumento das provas de função hepática e enzimáticas que se reduziu hipoteticamente com o tratamento com quercetina. Foram identificadas cirrose, congestão vascular porta e centrolobular na análise histopatológica por H&E e Picrosírius. CONCLUSÃO: O uso da quercetina diminuiu de maneira significante as alterações bioquímicas provocadas pela cirrose, aumentando o tempo de sobrevivência dos animais com cirrose biliar secundária à LDB, como verificado pelo teste de análise de sobrevivência.PURPOSE: The long term use of quercetin flavonoid was evaluated in cirrhotic rats by common biliary duct bondage (LDB. METHODS: 32 male Wistar rats were submitted to LDB or simulation, and distributed in 4 groups: 1 control, 2 cirrhotic, 3 cirrhotic treated with quercetin the second day after the surgical procedure; and 4 cirrhotic treated with quercetin after the fourteenth day of the surgical procedure. The hepatic

  15. Diabetes diminishes the portal-systemic collateral vascular response to vasopressin via vasopressin receptor and Gα proteins regulations in cirrhotic rats.

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    Jing-Yi Lee

    Full Text Available Liver cirrhosis may lead to portal-systemic collateral formation and bleeding. The hemostatic effect is influenced by the response of collateral vessels to vasoconstrictors. Diabetes and glucose also influence vasoresponsiveness, but their net effect on collaterals remains unexplored. This study investigated the impact of diabetes or glucose application on portal-systemic collateral vasoresponsiveness to arginine vasopressin (AVP in cirrhosis. Spraque-Dawley rats with bile duct ligation (BDL-induced cirrhosis received vehicle (citrate buffer or streptozotocin (diabetic, BDL/STZ. The in situ collateral perfusion was done after hemodynamic measurements: Both were perfused with Krebs solution, D-glucose, or D-glucose and NaF, with additional OPC-31260 for the BDL/STZ group. Splenorenal shunt vasopressin receptors and Gα proteins mRNA expressions were evaluated. The survival rate of cirrhotic rats was decreased by STZ injection. The collateral perfusion pressure changes to AVP were lower in STZ-injected groups, which were reversed by OPC-31260 (a V2R antagonist and overcome by NaF (a G protein activator. The splenorenal shunt V2R mRNA expression was increased while Gα proteins mRNA expressions were decreased in BDL/STZ rats compared to BDL rats. The Gαq and Gα11 mRNA expressions also correlated with the maximal perfusion pressure changes to AVP. Diabetes diminished the portal-systemic collateral vascular response to AVP in rats with BDL-induced cirrhosis, probably via V2 receptor up-regulation and Gα proteins down-regulation.

  16. [Cirrhotic cardiomyopathy: a specific entity].

    Science.gov (United States)

    Brondex, A; Arlès, F; Lipovac, A-S; Richecoeur, M; Bronstein, J-A

    2012-04-01

    Cirrhosis is a frequent and severe condition, which is the late stage of numerous chronic liver diseases. It is associated with major hemodynamic alterations characteristic of hyperdynamic circulation and with a series of structural, functional, electrophysiological and biological heart abnormalities termed cirrhotic cardiomyopathy. The pathogenesis of this syndrome is multifactorial. It is usually clinically latent or mild, likely because the peripheral vasodilatation significantly reduces the left ventricle afterload. However, sudden changes of hemodynamic state (vascular filling, surgical or transjugular intrahepatic porto-systemic shunts, peritoneo-venous shunts and orthotopic liver transplantation) or myocardial contractility (introduction of beta-blocker therapy) can unmask its presence, and sometimes convert latent to overt heart failure. Cirrhotic cardiomyopathy may also contribute to the pathogenesis of hepatorenal syndrome. This entity has been described recently, and its diagnostic criteria are still under debate. To date, current management recommendations are empirical, nonspecific measures. Recognition of cirrhotic cardiomyopathy depends on a high level of awareness for the presence of this syndrome, particularly in patients with advanced cirrhosis who undergo significant surgical, pharmacological or physiological stresses. PMID:22115174

  17. Management of cirrhotic ascites.

    Science.gov (United States)

    Pedersen, Julie Steen; Bendtsen, Flemming; Møller, Søren

    2015-05-01

    The most common complication to chronic liver failure is ascites. The formation of ascites in the cirrhotic patient is caused by a complex chain of pathophysiological events involving portal hypertension and progressive vascular dysfunction. Since ascites formation represents a hallmark in the natural history of chronic liver failure it predicts a poor outcome with a 50% mortality rate within 3 years. Patients with ascites are at high risk of developing complications such as spontaneous bacterial peritonitis, hyponatremia and progressive renal impairment. Adequate management of cirrhotic ascites and its complications betters quality of life and increases survival. This paper summarizes the pathophysiology behind cirrhotic ascites and the diagnostic approaches, as well as outlining the current treatment options. Despite improved medical treatment of ascites, liver transplantation remains the ultimate treatment and early referral of the patient to a highly specialized hepatology unit should always be considered. PMID:25954497

  18. Management of cirrhotic ascites

    DEFF Research Database (Denmark)

    Pedersen, Julie Steen; Bendtsen, Flemming; Møller, Søren

    2015-01-01

    in the natural history of chronic liver failure it predicts a poor outcome with a 50% mortality rate within 3 years. Patients with ascites are at high risk of developing complications such as spontaneous bacterial peritonitis, hyponatremia and progressive renal impairment. Adequate management of cirrhotic...... ascites and its complications betters quality of life and increases survival. This paper summarizes the pathophysiology behind cirrhotic ascites and the diagnostic approaches, as well as outlining the current treatment options. Despite improved medical treatment of ascites, liver transplantation remains...

  19. Early alterations of systemic and splanchnic hemodynamics after orthotopic liver transplantation in cirrhotic rats%肝硬化鼠肝移植后早期全身和内脏血流动力学的变化

    Institute of Scientific and Technical Information of China (English)

    曹晖; 吴志勇; 张效杰; 张海婴; 陈治平; 邝耀麟

    2001-01-01

    Objective The purpose of this study was to investigate early alterations of systemic and splanchnic hemodynamics after orthotopic liver transplantation (OLT) in normal and cirrhotic rats.Methods Male SD rats were divided into 4 groups: normal controls (NL,n=10),intrahepatic portal hypertension (IHPH,n=10) induced by CCl4,normal rats with OLT (NL-OLT,n=9) and IHPH rats with OLT (IHPH-OLT,n=16).Radioactive microsphere method was used for hemodynamic study.Results Increased cardiac output and splanchnic blood flow,decreased mean arterial blood pressure,total peripheral vascular resistance and splanchnic vascular resistance were found in IHPH,IHPH-OLT at day 3,and IHPH-OLT at day 7 in cirrhotic rats.The magnitude of hyperhemodynamic alterations was in the order of IHPH>IHPH-OLT (day 3) >IHPH-OLT (day 7) rats.Moreover,the derangement of splanchnic hyperhemodynamics was more significant than that of systemic hyperhemodynamics.Conclusions The results demonstrated that systemic and splanchnic hyperkinetic abnormalities seen in early liver transplantation may come from the pretransplant pathophysiologic status in cirrhotic rats.%目的观察正常鼠肝移植以及肝硬化鼠肝移植术后早期全身和内脏血流动力学的变化。方法实验动物随机分为正常鼠(NL,10只)、肝硬化鼠(IHPH,10只)、正常鼠肝移植(NL-OLT,9只)、肝硬化鼠肝移植(IHPH-OLT,16只)组。分别采用放射性微球法行血流动力学研究。结果 NL-OLT鼠绝大多数血流动力学参数与NL鼠比较差异无显著意义。IHPH及IHPH-OLT 3d,7d 组心输出量和内脏血流量增加,平均动脉压、周围血管总阻力和内脏血管阻力降低。内脏血流动力学紊乱较全身明显。结论肝硬化鼠肝移植后的血流动力学紊乱可能与移植前已存在的病理生理因素有关。

  20. Alpha-2A Adrenoceptor Agonist Guanfacine Restores Diuretic Efficiency in Experimental Cirrhotic Ascites: Comparison with Clonidine.

    Directory of Open Access Journals (Sweden)

    Giovanni Sansoè

    Full Text Available In human cirrhosis, adrenergic hyperfunction causes proximal tubular fluid retention and contributes to diuretic-resistant ascites, and clonidine, a sympatholytic drug, improves natriuresis in difficult-to-treat ascites.To compare clonidine (aspecific α2-adrenoceptor agonist to SSP-002021R (prodrug of guanfacine, specific α2A-receptor agonist, both associated with diuretics, in experimental cirrhotic ascites.Six groups of 12 rats were studied: controls (G1; controls receiving furosemide and potassium canrenoate (G2; rats with ascitic cirrhosis due to 14-week CCl4 treatment (G3; cirrhotic rats treated (over the 11th-14th CCl4 weeks with furosemide and canrenoate (G4, furosemide, canrenoate and clonidine (G5, or diuretics and SSP002021R (G6. Three rats of each group had their hormonal status and renal function assessed at the end of 11th, 12th, 13th, and 14th weeks of respective treatments.Cirrhotic rats in G3 and G4 gained weight over the 12th-14th CCl4 weeks. In G4, brief increase in sodium excretion over the 11th-12th weeks preceded worsening of inulin clearance and natriuresis (diuretic resistance. In comparison with G4, the addition of clonidine (G5 or guanfacine (G6 to diuretics improved, respectively, sodium excretion over the 11th-12th CCl4 weeks, or GFR and electrolytes excretion over the 13th-14th CCl4 weeks. Natriuretic responses in G5 and G6 were accompanied by reduced catecholamine serum levels.α2A-receptor agonists restore glomerular filtration rate and natriuresis, and delay diuretic-resistant ascites in experimental advanced cirrhosis. Clonidine ameliorates diuretic-dependent natriuresis just for a short time.

  1. New insights into cirrhotic cardiomyopathy

    DEFF Research Database (Denmark)

    Møller, Søren; Hove, Jens D; Dixen, Ulrik;

    2013-01-01

    Cirrhotic cardiomyopathy designates a cardiac dysfunction, which includes reduced cardiac contractility with systolic and diastolic dysfunction, and presence of electrophysiological abnormalities in particular prolongation of the QT interval. Several pathophysiological mechanisms including reduce...

  2. Melatonin protects the liver and erythrocytes against oxidative stress in cirrhotic rats Melatonina protege o fígado e eritrócitos do estresse oxidativo em ratos cirróticos

    Directory of Open Access Journals (Sweden)

    Darlan Pase da Rosa

    2010-03-01

    Full Text Available CONTEXT: Cirrhosis is a progressive chronic hepatopathy which constitutes an irreversible stage of liver dysfunction. OBJECTIVES: To evaluate the oxidative stress in the blood of cirrhotic rats treated with the antioxidant melatonin. METHODS: Cirrhosis was induced through inhalation of carbon tetrachloride. Liver integrity was evaluated by measuring serum enzymes, oxidative damage measured by lipoperoxidation, and antioxidant enzyme activity in erythrocytes. Lipoperoxidation, total nitrates, collagen, and histology by picrosirius staining were evaluated in the livers of these animals (n = 15, which were divided in three groups: control, carbon tetrachloride, and carbon tetrachloride + melatonin. Melatonin (20 mg/kg was administered intraperitoneal from week 10 of carbon tetrachloride inhalation. In order to shorten the cirrhosis induction time, phenobarbital (0.3 g/L was added to the animals' drinking water. RESULTS: A significant impairment in the liver integrity of melatonin-treated animals as compared to cirrhotic animals was observed. In rat erythrocytes and liver, lipoperoxidation was significantly increased in the cirrhotic rats as compared to controls, as measured through thiobarbituric acid reactive substances, and significantly decreased in melatonin-treated animals as compared to cirrhotic ones. In blood, a decrease in superoxide dismutase and glutathione peroxidase enzymes was detected in the cirrhotic group as compared to the control group, with increased superoxide dismutase activity when melatonin was administered. A reduction in the levels of total nitrates was detected in the hepatic tissue of the animals in the carbon tetrachloride group as compared to the control group and an increase of these levels in the carbon tetrachloride + melatonin group. As for hepatic collagen, we found a significant increase in the carbon tetrachloride group as compared to the controls and a regression of these values in the treated group. In

  3. [Management of umbilical hernia in cirrhotic patients].

    Science.gov (United States)

    Loriau, J; Manaouil, D; Mauvais, F

    2002-06-01

    The treatment of umbilical hernia in the setting of cirrhosis poses unique and specific management problems due to the pathophysiology of cirrhotic ascites. The high intra-abdominal pressures generated by ascites when applied to areas of parietal weakness are the cause of hernia formation and enlargement. Successful surgical treatment depends on minimization or elimination of ascites. Umbilical rupture and hernia strangulation are the most life-threatening complications of umbilical hernia with ascites and they demand urgent surgical intervention. In non-emergency situations, medical therapy to control ascites should precede hernia repair. When ascites is refractory to medical therapy, treatment will vary depending on whether transplantation is an option. In liver transplantation candidates, hernia repair can be performed at the end of the transplantation procedure. If transplanation is not envisaged, concomitant treatment of both ascites and hernia is best achieved by placement of a peritoneo-venous shunt at the time of the parietal repair. PMID:12391663

  4. [Adrenal insufficiency in cirrhotic patients].

    Science.gov (United States)

    Orozco, Federico; Anders, María; Mella, José; Antinucci, Florencia; Pagano, Patricia; Esteban, Paula; Cartier, Mariano; Romero, Gustavo; Francini, Bettina; Mastai, Ricardo

    2016-01-01

    Relative adrenal insufficiency (RAI) is a common finding in cirrhotic patients with severe sepsis, and increased mortality. Its significance is unknown in stable conditions. The aim of this study was to evaluate the prevalence of RAI in stable cirrhotic patients at different stages of the disease. Also, the impact of RAI on the survival was evaluated and basal cortisol levels between plasma and saliva was correlated in control subjects and cirrhotic patients. Forty seven ambulatory patients and 16 control subjects were studied. RAI was defined as a serum cortisol increase of less than 9 υg/dl from baseline after the stimulation with 250 mg of synthetic ACTH. Twenty two had Child-Pugh = 8 and 25 = 9. The prevalence of RAI in patients with stable cirrhosis was 22%. A higher incidence of RAI was observed in patients with a Child-Pugh = 9 (8/32) than in those with = 8 (3/13, p developed this complication (79% and 51%, p < 0.05, respectively). In summary, the prevalence of RAI is frequent in patients with stable cirrhosis and that it is related to the severity of liver diseaseand increased mortality. PMID:27576278

  5. Intrarenal octreotide treatment prevents sodium retention in liver cirrhotic rats: evidence for direct effects within the thick ascending limb of Henle's loop

    DEFF Research Database (Denmark)

    Jonassen, Thomas; Christensen, Sten; Marcussen, Niels;

    2006-01-01

    We have previously shown that systemic treatment with the somatostatin analog octreotide has marked beneficial effects on renal function in rats with liver cirrhosis induced by common bile duct ligation (CBL; Jonassen TEN, Christensen S, Sørensen AM, Marcussen N, Flyvbjerg A, Andreasen F, and Pet......We have previously shown that systemic treatment with the somatostatin analog octreotide has marked beneficial effects on renal function in rats with liver cirrhosis induced by common bile duct ligation (CBL; Jonassen TEN, Christensen S, Sørensen AM, Marcussen N, Flyvbjerg A, Andreasen F......, and Petersen JS. Hepatology 29: 1387-1395, 1999). In the present study, we tested the hypothesis that octreotide has a direct effect on renal tubular function. Rats (CBL or Sham-CBL) were intrarenally treated with low-dose octreotide in a long-acting release formulation, which had no systemic actions (100...... microg/kg body wt as a single dose). Rats receiving low-dose octreotide (sc) were used as controls. The rats were chronically instrumented, and renal function was examined 4 wk after CBL or Sham-CBL. Intrarenal octreotide administration (IROA) prevented sodium retention in CBL rats without changes...

  6. The role of vasoactive substance in hyperhemodynamics after orthotopic liver transplantation in cirrhotic rats%血管活性物质在肝硬化肝移植后高血流动力学中的作用

    Institute of Scientific and Technical Information of China (English)

    曹晖; 吴志勇; 等

    2001-01-01

    Objective To evaluate the role of endogenous vasoactive substancein hyperdynamic circulation after orthotopic liver transplantation (OLT) in cirrhotic rats. Methods Male SD rats were divided into 4 groups: normal controls (NL,10 rats), intrahepatic portal hypertension induced by injection of CCl4 (IHPH,10), normal rats with OLT (NL-OLT, 9), and IHPH rats with OLT (IHPH-OLT, 16). IHPH-OLT rats were divided into 2 subgroups: 3 days (Group A, 9 rats) and 7 days (Group B, 7) after OLT. OLT was performed in rats by using cuffs for the anastomosis of suprahepatic inferior vena cava, infrahepatic vena cava, and portal vein. Radioactive microsphere method was used for hemodynamic study.The concentrations of plasma glucagon(Glu), nitric oxide(NO), prostaglandin(PGI2, TXA2) and endothelin (ET) were measured by radioimmunoassay. Results No significant difference of hemodynamic changes was observed between NL-OLT and NL rats except mean arterial blood pressure. No significant changes of NO, PGI2 were seen between NL-OLT and NL rats. Glu, ET and TXA2 in NL-OLT rats were significantly elevated as compared to those in NL rats (P<0.05). There were characteristics of systemic and splanchnic hyperdynamic circulatory state in IHPH, IHPH-OLT A, IHPH-OLT B rats. Both the magnitude of hyperhemodynamics and increased concertrations of Glu and NO were in the order of IHPH>IHPH-OLT A>IHPH-OLT B rats. The level of plasma PGI2 in IHPH rats was significantly elevated compared to NL rats, while PGI2 in IHPH-OLT A rats, B was found significantly lower than that in IHPH rats (P<0.05). There was no significant difference of PGI2 between IHPH-OLT B and NL rats. Vasoconstrictors including ET and TXA2 were found elevated in IHPH-OLT rats. Conclusions Vasodilators including NO and Glu, especially NO play an important role in the hyperhemodynamics in IHPH and IHPH-OLT rats. The results of present study demonstrate that persistence of early systemic and splanchnic hyperkinetic circulation after OLT

  7. Adrenomedullin in cirrhotic and non-cirrhotic portal hypertension

    Institute of Scientific and Technical Information of China (English)

    V Tahan; C Kalayci; A Okten; N Tozun; E Avsar; C Karaca; E Uslu; F Eren; S Aydin; H Uzun; HO Hamzaoglu; F Besisik

    2003-01-01

    AIM:Adrenomedullin (ADM) is a potent vasodilator peptide.ADM and nitric oxide (NO) are produced in vascular endothelial cells. Increased ADM level has been linked to hyperdynamic circulation and arterial vasodilatation in cirrhotic portal hypertension (CPH). The role of ADM in non-cirrhotic portal hypertension (NCPH) is unknown, plasma ADM levels were studied in patients with NCPH, compensated and decompensated cirrhosis in order to determine its contribution to portal hypertension (PH) in these groups.METHODS: There were 4 groups of subjects. Group 1consisted of 27 patients (F/M: 12/15) with NCPH due to portal and/or splenic vein thrombosis (mean age: 41±12years), group 2 consisted of 14 patients (F/M: 6/8) with compensated (Child-Pugh A) cirrhosis (mean age: 46±4),group 3 consisted of 16 patients (F/M: 6/10) with decompensated (Child-Pugh C) cirrhosis (mean age: 47±12).Fourteen healthy subjects (F/M: 6/8) (mean age: 44±8) were used as controls in Group 4. ADM level was measured by ELISA. NO was determined as nitrite/nitrate level by chemoluminescence.RESULTS: Adl level in Group 11 (236±61.4 pg/mL) was significantly higher than that in group 2 (108.4±28.3 pg/mL)and group 4 (84.1±31.5 pg/mL) (both P<0.0001) but was lower than that in Group3 (324±93.7 pg/mL) (P=0.002). NO level in group 1 (27±1.4 μmol/L) was significantly higher than that in group 2 (19.8±2.8 μmol/L) and group 4 (16.9±1.6μmol/L) but was lower than that in Group 3 (39±3.6 μmol/L)(for all three P<0.0001). A strong correlation was observed between ADM and NO levels (r=0.827, P<0.0001).CONCLUSION: Adrenomedullin and NO levels were high in both non-cirrhotic and cirrhotic portal hypertension and were closely correlated, Adrenomedullin and NO levels increased proportionally with the severity of cirrhosis, and were significantly higher than those in patients with NCPH.Portal hypertension plays an important role in the increase of ADM and NO. Parenchymal damage in cirrhosis may

  8. Partial splenic artery embolization in cirrhotic patients

    OpenAIRE

    Hadduck, Tyson A; McWilliams, Justin P.

    2014-01-01

    Splenomegaly is a common sequela of cirrhosis, and is frequently associated with decreased hematologic indices including thrombocytopenia and leukopenia. Partial splenic artery embolization (PSE) has been demonstrated to effectively increase hematologic indices in cirrhotic patients with splenomegaly. This is particularly valuable amongst those cirrhotic patients who are not viable candidates for splenectomy. Although PSE was originally developed decades ago, it has recently received increase...

  9. Desensitization of G-protein-coupled receptors induces vascular hypocontractility in response to norepinephrine in the mesenteric arteries of cirrhotic patients and rats

    Institute of Scientific and Technical Information of China (English)

    Wei Chen; Jiang-Yong Sang; De-Jun Liu; Jun Qin; Yan-Miao Huo; Jia Xu and Zhi-Yong Wu

    2013-01-01

    BACKGROUND: The  increased  β-arrestin-2  and  its  combina-tion with G-protein-coupled receptors (GPCRs) lead to GPCRs desensitization.  The  latter  may  be  responsible  for  decreased contractile  reactivity  in  the  mesenteric  arteries  of  cirrhotic patients  and  rats.  The  present  study  is  to  investigate  the machinery  changes  of  α-adrenergic  receptors  and  G  proteins and  their  roles  in  the  contractility  of  mesenteric  arteries  of cirrhotic patients and animal models. METHODS: Patients  with  cirrhosis  due  to  hepatitis  B  and cirrhotic rats induced by CCl4 were studied. Mesenteric artery contractility  in  response  to  norepinephrine  was  determined by  a  vessel  perfusion  system.  The  contractile  effect  of  G protein-coupled  receptor  kinase-2  (GRK-2)  inhibitor  on  the mesenteric artery was evaluated. The protein expression of the α1 adrenergic receptor, G proteins, β-arrestin-2, GRK-2 as well as  the  activity  of  Rho  associated  coiled-coil  forming  protein kinase-1 (ROCK-1) were measured by Western blot. In addition, the interaction of α1 adrenergic receptor with β-arrestin-2 was assessed by co-immunoprecipitation. RESULTS: The  portal  vein  pressure  of  cirrhotic  patients  and rats  was  significantly  higher  than  that  of  controls.  The  dose-response curve to norepinephrine in mesenteric arteriole was shifted  to  the  right,  and  EC50  was  significantly  increased  in cirrhotic patients and rats. There were no significant differences in the expressions of the α1 adrenergic receptor and G

  10. Ayurvedic management of cirrhotic ascites.

    Science.gov (United States)

    Aswathy, G; Dharmarajan, Prasanth; Sharma, Ananth Ram; Sasikumar, V K; Vasudevan Nampoothiri, M R

    2016-01-01

    Cirrhosis is the final stage of most of the chronic liver diseases and is most invariably complicated by portal hypertension resulting in ascites. A case of chronic liver disease with portal hypertension (cryptogenic cirrhosis), managed at Amrita School of Ayurveda is discussed in this paper. The clinical picture was that of an uncomplicated cirrhotic ascites. Snehapāna (therapeutic oral administration of lipids) followed by virecana (purgation) was done after an initial course of nityavirecana (daily purgation). Later Vardhamāna pippalī rasāyana [administration of single drug - pippalī (piper longum) in a structured dose pattern] was administered with an intention of rejuvenating liver cells. Ascites and lower limb oedema were completely resolved after the therapy. No recurrence of ascites has been reported after a follow up period of one year. PMID:27621523

  11. Effects of nitric oxide synthase inhibitor in two-week oral treatment on hyperdynamic circulatory state in cirrhotic rats%一氧化氮合酶抑制剂口服两周治疗对肝硬化大鼠高动力循环状态的影响

    Institute of Scientific and Technical Information of China (English)

    黄颖秋; 萧树东; 莫剑忠; 张德中

    2000-01-01

    To investigate the effects of low dosage of nitric oxide synthase (NOS) inhibitor Nc-nitro -L-arginine methyl ester ( L-NAME) in two-week treatment on the hyperdynamic circulatory state in rats with cirrhosis. METHODS: Cirrhosis model was induced in male SD rats by injection of 60 % CCL4 oily solution subcutaneously. Cirrhotic rats were treated with L-NAME ( 0.5 mg·kg-1·d-1) by gavage for two weeks. Mean arterial pressure ( AP ), portal pressure(PP), cardiac output ( CO ), cardiac index ( CI ), splanchnic vascular resistance ( SVR ), splanchnic blood flow(SBF) and serum nitrite levels were determined in L-NAME-treated, L-NAME-untreated cirrhotic rats and controls by using 57Co-labled microsphere technique and a fluorometric assay, respectively. RESULTS: Untreated cirrhotic rats had significantly lower MAP, SVR and higher PP, CO, CI, SBF and nitrite concentration than those of the controls (all,P< 0.01 ). In treated cirrhotic rats, L-NAME significantly attenuated the increase of CO, CI, SBF, nitrite concentration and the decrease of MAP and SVR. In treated cirrhotic rats, L-NAME induced a marked decrease of nitrite concentration than untreated cirrhotic rats[(1.471±0.907)μmol/L vs (4.204±1.253) μmol/L, P<0.01]. CONCLUSION: The endogenous NO may play an important role in the changes of hemodynamics pattern in cirrhosis, and hyperdynamic circulatory state in rats with cirrhosis can be ameliorated by oral two-week administration of lower dose of L-NAME.%目的:观察小剂量一氧化氮合酶(N0S)抑制剂N-硝基-L-精氨酸甲酯(L-NAME)连续2周治疗对肝硬化大鼠高动力循环状态的影响.方法:用60%四氯化碳油性溶液皮下注射SD大鼠制造肝硬化大鼠模型.对肝硬化大鼠,用L-NAME(0.5mg·kg·d-1)胃管内注入连续治疗2周.用57Co同位素微球技术分别测定L-NAME治疗组、未治疗组及正常对照组的平均动脉压(MAP)、门静脉压(PP)、心输出量(C0)、心脏指数(CI)、内脏血管阻力(SVR)及内脏

  12. Effect of liver ischemic preconditioning in cirrhotic rats submitted to hepatic ischemia/reperfusion injury Efeito do pré-condicionamento isquêmico hepático submetidos a lesão de isquemia/reperfusão do fígado

    Directory of Open Access Journals (Sweden)

    Eduardo Garcia Pacheco

    2006-01-01

    Full Text Available PURPOSE: The main aim of this study was to determine the influence of ischemic preconditioning (IPC on rat liver cirrhosis. METHODS: Cirrhosis was induced in Wistar rats by occlusion of the hepatic duct. The animals were divided into four groups of six animals each: non-cirrhotic group (simulated operation only, cirrhotic control group (simulated operation in cirrhotic rats, I/R group (40-minute ischemia without IPC, and IPC group (cirrhotic rats with ischemia, previously submitted to IPC. The IPC procedure consisted of partial hepatic ischemia for five minutes, followed by 10 minutes of reperfusion. In the case of the IPC group, the animals were submitted to liver ischemia for 40 minutes after the preconditioning procedure, followed by 2 hours of reperfusion. Blood samples were collected for measurement of serum aminotransferases (ALT and AST. The respiratory control ratio (RCR, the mitochondrial membrane potential (MMP, and malondialdehyde (MDA values in the hepatic tissue were analyzed. Nonparametric statistical analysis was used and a value of pOBJETIVO: O objetivo deste estudo foi determinar a influência do pré-condicionamento isquêmico (IPC em fígados de ratos cirróticos. MÉTODOS: A cirrose hepática foi induzida em ratos Wistar machos (250 a 300g por oclusão, durante 30 dias, do ducto hepático comum.A seguir, os animais cirróticos foram divididos em três grupos de seis; Grupo controle cirrótico (operação simulada para isquemia/reperfusão/pré-condicionamento, Grupo I/R, isquemia de 40 minutos sem pré-condicionamento (IPC e grupo IPC com isquemia precedida por IPC. O IPC consistiu de uma isquemia parcial por cinco minutos, seguida por 10 minutos de reperfusão. No grupo IPC, após o pré-condicionamento, os animais foram submetidos à isquemia hepática de 40 minutos seguida de 2 horas de reperfusão. Foram colhidas amostras de sangue para dosagem sérica de aminotransferases (ALT e AST. Razão de controle respiratório (RCR

  13. The role of hydrogen peroxide on mesenteric artery RhoA/ROCK signal pathway in cirrhotic rats with portal hypertension%过氧化氢在肝硬化门静脉高压症大鼠肠系膜动脉RhoA/ROCK信号通路中的作用

    Institute of Scientific and Technical Information of China (English)

    段明; 刘德军; 秦骏; 吴志勇; 罗蒙; 陈炜

    2014-01-01

    目的 探讨过氧化氢(H2O2)对胆总管结扎诱导的肝硬化门静脉高压症(PHT)大鼠肠系膜动脉收缩反应性的影响及其在RhoA/Rho激酶(ROCK)信号通路中的作用机制.方法 结扎胆总管建立肝硬化门静脉高压症大鼠模型.每日1次腹腔内注射生理盐水或聚乙二醇-过氧化氢酶(PEG-catalase,10 000 U/kg)共8d,相应处理正常大鼠.测定肠系膜动脉H2O2含量,利用血管灌流系统测定肠系膜微动脉对去甲肾上腺素的反应.检测大鼠肠系膜动脉α1肾上腺素能受体和β-arrestin2蛋白表达及其相互作用的变化,以及肠系膜动脉内ROCK-1蛋白量和活性的变化.结果 肝硬化PHT大鼠的离体肠系膜微动脉对去甲肾上腺素剂量反应曲线右移,EC50升高,PEG-catalase降低动脉过氧化氢含量后能逆转上述表现.各组肠系膜动脉的α1肾上腺素能受体含量不变.但是,PEG-cat-alase处理后肝硬化PHT大鼠肠系膜动脉内β-arrestin-2蛋白量降低,与α1肾上腺素能受体结合程度也降低;PHT大鼠肠系膜动脉内ROCK-1蛋白含量及其活性明显升高.结论 肝硬化PHT肠系膜动脉H2O2含量升高,引起抑制蛋白β-arrestin-2水平上升,与α1肾上腺素能受体结合能力增强,使得ROCK蛋白含量和活性均明显下降,造成肠系膜动脉对缩血管物质的收缩低反应性.%Objective To explore the role of hydrogen peroxide in mesenteric artery contraction of cirrhotic rats with portal hypertension,which was induced by bile duct ligation.Possible mechanism in RhoA/ROCK signal pathway was also part of the focus.Methods The bile duct ligation-induced cirrhotic rats and normal rats (control group) were treated equally with PEG-catalase(10 000 U/kg-1 · d-1,ip.) or by its vehicle for 8 days.Then the level of H2O2 in mesenteric arteries was detected.The contractile response to norepinephrine of arterioles was analyzed by vascular perfusion system.The protein expressions of the α1 adrenergic receptor

  14. Prognostic indicators in alcoholic cirrhotic men

    DEFF Research Database (Denmark)

    Gluud, C; Henriksen, J H; Nielsen, G

    1988-01-01

    The relationships between portal pressure, liver function and clinical variables on one hand and development of variceal hemorrhage and death on the other were investigated in 58 men with newly diagnosed alcoholic cirrhosis. Portal pressure was determined during hepatic vein catheterization as...... prognosis in alcoholic cirrhotic men may be significantly improved by information about size of esophageal varices and level of portal pressure....

  15. Load-dependent growth of rat tibia

    Science.gov (United States)

    Ohira, Y.; Kawano, F.; Wang, X. D.; Lan, Y. B.; Ishihara, A.; Iwashita, Y.; Majima, H. J.; Nonaka, I.

    Effects of hindlimb suspension or 2-G loading from the postnatal day 4 to month 3 followed by 3 month recovery on tibia and ankle joint mobility were investigated in rats. The dorsiflexion of the ankle was inhibited in the suspended group and such phenomena were irreversible. The growth-related increases of weight and bone mineral density were inhibited by unloading. They were increased gradually, but did not reach the age-matched control levels even after 3 months. Growth of bone length was not affected by unloading. External bending of the shaft and rotation of distal end of tibia were observed in the suspended group and these phenomena did not recover at all. It was suggested that the inhibited dorsiflexion of ankle joints was closely related to such morphological changes. It was further suggested that the unloading-related changes in bone morphology may be caused by abnormal mechanical stress applied by muscles with altered patterns. None of the parameters were influenced by 2-G loading, may be because the mechanical stress applied to bones could be identical at 1- and 2-G, if the rats maintain their posture in a recumbent position with fully dorsiflexed ankle joints.

  16. Dobutamine stress echocardiography for evaluating cirrhotic cardiomyopathy in liver cirrhosis

    OpenAIRE

    Kim, Moon Young; Baik, Soon Koo; Won, Chan Sik; Park, Hong Jun; Jeon, Hyo Keun; Hong, Hyun Il; Kim, Jae Woo; Kim, Hyun Soo; Kwon, Sang Ok; Kim, Jang Young; Yoo, Byung Su; Lee, Seung Hwan

    2010-01-01

    Background/Aims The blunted ventricular systolic and diastolic contractile responses to physical and pharmacological stress in cirrhosis are termed cirrhotic cardiomyopathy (CCM). CCM has been known to involve multiple defects in the β-adrenergic signaling pathway. The aim of this study was to determine whether cirrhotic patients have blunted cardiac responses to catecholamine stimulation through dobutamine stress echocardiography (DSE). Methods Seventy-one cirrhotic patients with normal left...

  17. Partial splenic artery embolization in cirrhotic patients

    Science.gov (United States)

    Hadduck, Tyson A; McWilliams, Justin P

    2014-01-01

    Splenomegaly is a common sequela of cirrhosis, and is frequently associated with decreased hematologic indices including thrombocytopenia and leukopenia. Partial splenic artery embolization (PSE) has been demonstrated to effectively increase hematologic indices in cirrhotic patients with splenomegaly. This is particularly valuable amongst those cirrhotic patients who are not viable candidates for splenectomy. Although PSE was originally developed decades ago, it has recently received increased attention. Presently, PSE is being utilized to address a number of clinical concerns in the setting of cirrhosis, including: decreased hematologic indices, portal hypertension and its associated sequela, and splenic artery steal syndrome. Following PSE patients demonstrate significant increases in platelets and leukocytes. Though progressive decline of hematologic indices occur following PSE, they remain improved as compared to pre-procedural values over long-term follow-up. PSE, however, is not without risk and complications of the procedure may occur. The most common complication of PSE is post-embolization syndrome, which involves a constellation of symptoms including fever, pain, and nausea/vomiting. The rate of complications has been shown to increase as the percent of total splenic volume embolized increases. The purpose of this review is to explore the current literature in regards to PSE in cirrhotic patients and to highlight their techniques, and statistically summarize their results and associated complications. PMID:24876920

  18. Postmortem regional distribution of morphine in dependent rats

    Institute of Scientific and Technical Information of China (English)

    王惠玲; 马丽霞; 唐承汉; 赵晏

    2003-01-01

    Objective: Morphine concentration measured in postmortem tissues may or may not reflect antemortem concentration. We measured levels of morphine in autopsied tissues to determine whether morphine distribution in morphine-dependent rats is altered after death. Methods: Solid-phase extraction was used to extract morphine from the samples, and morphine levels were measured at 0-96 h postmortem using gas chromatography. Results: The study of the morphine dependent rats showed a significant (P<0.05) increase of morphine concentration in postmortem cardiac blood, liver tissues and kidneys tissues. A significant increase was also observed at 72 h and 96 h postmortem in the brain, while morphine levels in cardiac tissues only increased at 24 h and 96 h postmortem. These changes were associated with an observed pH rapid decrease: pH of cardiac blood dropped from 7.36±0.15 to 6.86±0.09 (P<0.01), pH of liver tissues from 6.98±0.04 to 6.34±0.03 (P<0.05). Conclusion: The postmortem regional distribution of morphine occurs in dependent rats, but different from the change that occurs in acute poisoning rats. The morphine concentration in cardiac blood and tissues tends to increase during the period of 0-96 h postmortem in dependent rats. Morphine concentration increases with pH rapid decrease. The antemortem internal amount of morphine affects its postmortem regional distribution. It appears that several mechanisms are accountable for postmortem morphine distribution. The understanding of the mechanisms and patterns may eventually lead to better choices of samples which may better represent antemortem drug levels.

  19. Hemoperitoneum in cirrhotic patients without abdominal trauma or tumor

    Institute of Scientific and Technical Information of China (English)

    Yuan-Ji Ma; En-Qiang Chen; Jia-Jie Lu; Ming-Zhen Tan; Hong Tang

    2011-01-01

    BACKGROUND: Hemoperitoneum is associated with several emergency conditions and is especially evident when it occurs in patients with liver cirrhosis. This study aimed to assess the clinical characteristics of cirrhotic patients who did not have abdominal trauma or tumor but who developed hemoperitoneum. METHODS: Wereviewedtheclinicalrecordsof1276consecutive cirrhotic patients with hemoperitoneum at our center between January 2007 and December 2009. Hemoperitoneum was confirmed by abdominal paracentesis. RESULTS: Of the 1276 cirrhotic patients, 19 were found to have hemoperitoneum, but only 6 did not have abdominal trauma or tumor. The occurrence of spontaneous hemoperitoneum in the cirrhotic patients was therefore 0.5%. Hemoperitoneum can occur spontaneously in severely decompensated cirrhotic patients with intra-abdominal collateral vessels and high scores on the model for end-stage liver disease and Child-Pugh-Turcotte test. Most patients presented with abdominal distension, abdominal pain, increased abdominal girth and hemodynamic instability with a significant drop in the hemoglobin level. Three patients died of hemorrhagic shock within 24 hours, and the other 3 died of hepatic encephalopathy or spontaneous bacterial peritonitis after 5 to 10 days because of further decompensation of the liver. CONCLUSIONS: Hemoperitoneum can occur in cirrhotic patients who do not have abdominal trauma or tumor. It mainly occurs in severely decompensated end-stage cirrhotic patients. Cirrhotic patients with hemoperitoneum have a poor prognosis.

  20. Mechanisms underlying epithelium-dependent relaxation in rat bronchioles

    DEFF Research Database (Denmark)

    Kroigaard, Christel; Dalsgaard, Thomas; Simonsen, Ulf

    2010-01-01

    This study investigated the mechanisms underlying epithelium-derived hyperpolarizing factor (EpDHF)-type relaxation in rat bronchioles. Immunohistochemistry was performed, and rat bronchioles and pulmonary arteries were mounted in microvascular myographs for functional studies. An opener of small...... (SK(Ca)) and intermediate (IK(Ca))-conductance calcium-activated potassium channels, NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) was used to induce EpDHF-type relaxation. IK(Ca) and SK(Ca)3 positive immunoreactions were observed mainly in the epithelium and endothelium of bronchioles and arteries......, respectively. In 5-hydroxytryptamine (1 microM)-contracted bronchioles (828 +/- 20 microm, n = 84) and U46619 (0.03 microM)-contracted arteries (720 +/- 24 microm, n = 68), NS309 (0.001-10 microM) induced concentration-dependent relaxations that were reduced by epithelium/endothelium removal and by blocking IK...

  1. 内皮素受体拮抗剂对肝硬化大鼠转化生长因子β1和Ⅰ型胶原mRNA表达的影响%Effects of ET receptor antagonist on expression of TGFβ1 and collagen type Ⅰ mRNA in hepatic cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    陈汇; 许冰

    2011-01-01

    Aim; To investigate the effects of ET receptor antagonist on the expression of collagen type I and TGFpl mRNA in carbon tetrachloride-induced cirrhosis rats. Methods: A total of 40 male SD rats were allocated into carbon tetra-chloride group, normal group,endothelin A receptor antagonist group, endothelin B receptor antagonist group,and combined treatment group. The posterior 3 groups were injected with BQ-123( 12.5 μg/kg) ,BQ-788(15 μg/kg) ,and BQ-123 + BQ-788 .respectively,besides carbon tetrachloride treatment. The expressions of collagen type I and TGF(31 mRNA were determined by RT-PCR. And a specific portion of liver tissue in every group was took for routine pathology testing. Results:The expression of TGF|31 mRNA in 5 groups had no significant difference( F = 1. 857 ,P = 0. 765 ) , but that of collagen type I mRNA in 5 groups[ (0.437 ±0.082) ,(0.623 ±0.142) , (0.655 ±0. 124) , (0.558 ±0.183), and (0.874 ±0. 170)] had significant differences ( F = 11. 235 ,P =0. 023) . Microscopic image showed that inflammatory reaction decreased in the cirrhotic rats with injection of both ET receptor antagonists or combination administration. Conclusion: Endothelin receptor antagonists could inhibit the expression of hepatic collagen typelin cirrhotic rats effectively, and reduce inflammation reaction and liver fibrosis.%目的:探讨内皮素受体拮抗剂对肝硬化大鼠转化生长因子β1和I型胶原mRNA表达的影响.方法:40只雄性SD大鼠,随机分成四氯化碳组、正常对照组、内皮素A受体拮抗剂治疗组、内皮素B受体拮抗剂治疗组和联合治疗组5组,每组8只.后3组在四氯化碳灌胃的基础上2次/d(间隔10 h)分别皮下注射BQ-123(12.5μg/kg)和BQ-788(15μg/kg)以及BQ-123+ BQ-788(12.5 μg/kg+ 15 μg/kg).取部分肝组织进行常规病理学检测,部分采用RT-PCR测定大鼠肝组织转化生长因子β1和I型胶原mRNA表达水平.结果:常规病理结果显示内皮素受体拮抗剂处理组肝脏炎

  2. Stigma in Cirrhotic Patients: A Qualitative Study.

    Science.gov (United States)

    Shabanloei, Reza; Ebrahimi, Hossein; Ahmadi, Fazlollah; Mohammadi, Eesa; Dolatkhah, Roya

    2016-01-01

    Stigma is one of the main problems of patients suffering from cirrhosis, and it causes many challenges for the patients and their treatment. The present study aimed to discover and define the perceived stigma by cirrhotic patients. This qualitative study was conducted through a content analysis approach. The participants were 15 patients suffering from cirrhosis. Data were collected via semistructured, in-depth interviews and analyzed on the basis of methods described by Granheme and Landman. During data analysis, stigma was categorized into four categories and 13 subcategories: external representation of social stigma (others' avoidance behaviors, inadmissible tag, discriminative behaviors of treatment personnel, blaming behaviors), internal representation of social stigma (social ostracism, social isolation, curiosity to perceive people's perceptions), external representation of self-stigma (fear of disclosure of illness, threatening situation, difficult emotional relationships), and internal representation of self-stigma (condemned to suffer, self-punishment, self-alienation). Experiencing stigma is common among cirrhotic patients and may affect patients' coping with the illness and treatment. Thus, it is specifically important that treatment personnel know patients' perception, provide comprehensive support for these patients, and plan to enhance public awareness about the disease recommended. PMID:27258462

  3. The Diminished Expression of Proangiogenic Growth Factors and Their Receptors in Gastric Ulcers of Cirrhotic Patients

    OpenAIRE

    Jiing-Chyuan Luo; Yen-Ling Peng; Ming-Chih Hou; Kuang-Wei Huang; Hui-Chun Huang; Ying-Wen Wang; Han-Chieh Lin; Fa-Yauh Lee; Ching-Liang Lu

    2013-01-01

    OBJECTIVES: The pathogenesis of the higher occurrence of peptic ulcer disease in cirrhotic patients is complex. Platelets can stimulate angiogenesis and promote gastric ulcer healing. We compared the expressions of proangiogenic growth factors and their receptors in the gastric ulcer margin between cirrhotic patients with thrombocytopenia and those of non-cirrhotic patients to elucidate possible mechanisms. METHODS: Eligible cirrhotic patients (n = 55) and non-cirrhotic patients (n = 55) who ...

  4. Testosterone supports hormone-dependent aggression in female rats.

    Science.gov (United States)

    Albert, D J; Jonik, R H; Walsh, M L; Petrovic, D M

    1989-08-01

    Female hooded rats were ovariectomized and implanted with a single testosterone-filled Silastic tube or an empty tube. The tube size was one which allowed a release of testosterone at the high end of the mean normal serum testosterone concentration for intact females. Following a 7-day recovery period, all rats were placed on a 23-hr food-deprivation schedule and adapted to a highly palatable liquid food over a 5-day period. Each animal with a testosterone implant was then housed with an animal of similar weight but an empty implant. The pairs were subjected to a series of 3 restricted-access competition tests (1/day) followed 4 days later by a series of 3 free-access competition tests. The animals were then separated, adapted to a bland liquid food, and paired with new partners. They were then subjected to the restricted- and free-access food-competition tests but with bland food as the incentive. During the first 6 competition tests there were no significant differences between groups in aggression or in time spent licking at the food spout. During the second series of tests, females with testosterone implants were more aggressive and more successful at maintaining access to the food than were their competitors with empty implants. The difference between groups occurred during the free- as well as the restricted-access tests. The effectiveness of physiological levels of testosterone in supporting aggression is attributed to the use of a test situation that activates as well as elicits hormone-dependent aggression. These results suggest that testosterone may be the hormonal substrate for hormone-dependent aggression in female rats.

  5. Nutritional assessment in cirrhotic patients with hepaticencephalopathy

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatic encephalopathy (HE) is one of the worstcomplications of liver disease and can be greatly influencedby nutritional status. Ammonia metabolism, inflammationand muscle wasting are relevant processes inHE pathophysiology. Malnutrition worsens the prognosisin HE, requiring early assessment of nutritional statusof these patients. Body composition changes inducedby liver disease and limitations superimposed by HEhamper the proper accomplishment of exams in thispopulation, but evidence is growing that assessmentof muscle mass and muscle function is mandatory dueto the role of skeletal muscles in ammonia metabolism.In this review, we present the pathophysiologicalaspects involved in HE to support further discussionabout advantages and drawbacks of some methods forevaluating the nutritional status of cirrhotic patients withHE, focusing on body composition.

  6. [Chylothorax of cirrhotic origin: a case report].

    Science.gov (United States)

    Vandenbos, F; Rakotoarisoa, C; Zeanandin, G; Mourani, A

    2005-12-01

    Chylothorax and chylous ascites are an accumulation of fluid containing a large proportion of triglycerides. The presence of these two effusions simultaneously is rare. A case of a patient with a known history of cirrhosis, hospitalized for an ascetic decompensation with left pleural effusion is herein presented. The woman was diagnosed as presenting both chylous ascites and chylothorax. Both fluids are transudate type fluids. After evacuation of the fluids and implementation of an adapted treatment neither effusion reappeared. The patient has been followed for the past year and has not shown any signs of relapse. Chylothorax, in cirrhotic patients is due to trans-diaphragmatic passage of fluid originating from the chylous ascites. Both extravasations have the same biological characteristics. PMID:16449926

  7. Effect of biliary cirrhosis on nonadrenergic noncholinergic-mediated relaxation of rat corpus cavernosum: Role of nitric oxide pathway and endocannabinoid system

    Directory of Open Access Journals (Sweden)

    Dehpour A.R.

    2008-06-01

    Full Text Available Background: Relaxation of the corpus cavernosum plays a major role in penile erection. Nitric oxide (NO is known to be the most important factor mediating relaxation of corpus cavernosum, which is mainly derived from nonadrenergic noncholinergic (NANC nerves. The aim of the present study was to investigate the effect of biliary cirrhosis on nonadrenergic noncholinergic (NANC-mediated relaxation of rat corpus cavernosum as well as the possible relevant roles of endocannabinoid and nitric oxide systems.Methods: Corporal strips from sham-operated and biliary cirrhotic rats were mounted under tension in a standard oxygenated organ bath with guanethidine sulfate (5 µM and atropine (1 µM to induce adrenergic and cholinergic blockade. The strips were precontracted with phenylephrine hydrochloride (7.5 µM and electrical field stimulation was applied at different frequencies (2, 5, 10, 15 Hz to obtain NANC-mediated relaxation. In separate precontracted strips of the sham and cirrhotic groups, the concentration-dependent relaxant responses to sodium nitroprusside (10 nM-1mM, as an NO donor, were assessed.  Results: The NANC-mediated relaxation was significantly enhanced in cirrhotic animals (P<0.01. Anandamide potentiated the relaxations in both groups (P<0.05. The cannabinoid CB1 receptor antagonist AM251 (10 µM and the vanilloid receptor antagonist capsazepine (10 µM each significantly prevented the enhanced relaxations in cirrhotic rats (P<0.01. The CB2 receptor antagonist AM630 had no effect on relaxations in the cirrhotic group. In a concentration-dependent manner, L-NAME (30-1000 nM inhibited relaxations in both the sham and cirrhotic groups, although cirrhotic groups were more resistant to the inhibitory effects of L-NAME. The degree of relaxation induced by sodium nitroprusside (10 nM-1 mM was similar in the two groups.Conclusions: Biliary cirrhosis enhances the neurogenic relaxation in rat corpus cavernosum probably via the NO pathway and

  8. 苯巴比妥联合 CCl4法建立肝硬化腹水大鼠模型%To establish the model of cirrhotic rats with ascites phenobarbital combined with CCl4 method

    Institute of Scientific and Technical Information of China (English)

    方庆; 王成业; 姚瑶; 王满媛; 许钒

    2015-01-01

    Objective To establish a stable rat model of liver cirrhosis by using carbon tetrachloride combined with Phenobarbital Sodi-um.Methods 35%Phenobarbital Sodium was carried out in SD rats for 7 days to activate hepatic microsomal enzyme P450.From the second week,gradient carbon tetrachloride oil solution was offered by intraperitoneal injection (twice per week for 14 weeks).24 h u-rine of rats was collected and measured at the end time of the trial.HE staining of liver tissue was used to observe pathological process of liver.Results After induced with Phenobarbital Sodium for 7 days and then injected with carbon tetrachloride into abdominal cavity continuously for 13 weeks,a stable rat model of liver cirrhosis could be achieved.Conclusion The procedure is stable and reliable for building liver cirrhosis model,and the model has lower mortality and shorter cycle time than traditional one.%目的:采用苯巴比妥联合四氯化碳构建稳定的肝硬化腹水大鼠模型,为抗肝硬化腹水药物的研究提供有效可靠的动物模型。方法采用苯巴比妥联合CCl4法复制肝硬化腹水大鼠模型。35%苯巴比妥溶液诱导1周,激活肝脏肝药酶P450活性,第二周开始,按梯度腹腔注射CCl4油溶液,每周2次至第14周。实验进行至中后期,收集大鼠24 h尿液,测量尿量;检查腹腔积液量;肝组织HE染色观察肝脏病理进程。结果大鼠经苯巴比妥溶液诱导1周后,连续腹腔注射CCl4油溶液13周,可复制稳定的肝硬化腹水模型。结论该法可建立稳定、可靠的肝硬化腹水模型,比传统模型降低了死亡率,且造模时间缩短。

  9. Time-dependent viscoelastic properties along rat small intestine

    Institute of Scientific and Technical Information of China (English)

    James B Smith; Jing-Bo Zhao; Yan-Ling Dou; Hans Gregersen

    2005-01-01

    AIM: To measure the time-dependent (viscoelastic)behavior in the change of the small intestinal opening angle and to test how well the behavior could be described by the Kelvin model for a standard linear solid.METHODS: Segments from the duodenum, jejunum, and ileum were harvested from 10 female Wistar rats and the luminal diameter, wall thickness, and opening angleover time (θ(t)) were measured from rings cut from thesesegments.RESULTS: Morphometric variations were found along thesmall intestine with an increase in luminal area and adecrease in wall thickness from the duodenum to theileum. The opening angle obtained after 60 min washighest in the duodenum (220.8±12.9°) and decreasedalong the length of the intestine to 143.9±8.9° in the jejunum and 151.4±9.4° in the ileum. The change ofopening angle as a function of time, fitted well to theKelvin model using the equation θ(t)/θo = [1-ηexp (-λt)]after the ring was cut. The computed creep rate λ did notdiffer between the segments. Compared to constantcalculated from pig aorta and coronary artery, it showedthat α agreed well (within 5%), η was three times largerthan that for vascular tissue, and λ ranged ±40% from the value of the pig coronary artery and was a third of the value of pig aorta.CONCLUSION: The change of opening angle over timefor all the small intestine segments fits well to the standardlinear spring-dashpot model. This viscoelastic constantof the rat small intestine is fairly homogenous along itslength. The data obtained from this study add to a baseset of biomechanical data on the small intestine andprovide a reference state for comparison to other tissues,diseased intestinal tissue or intestinal tissue exposed todrugs or chemicals.

  10. Jejunal microvilli atrophy and reduced nutrient transport in rats with advanced liver cirrhosis: improvement by Insulin-like Growth Factor I

    Directory of Open Access Journals (Sweden)

    Castilla-Cortázar Inma

    2004-06-01

    Full Text Available Abstract Background Previous results have shown that in rats with non-ascitic cirrhosis there is an altered transport of sugars and amino acids associated with elongated microvilli. These alterations returned to normal with the administration of Insulin-Like Growth Factor-I (IGF-I. The aims of this study were to explore the evolution of these alterations and analyse the effect of IGF-I in rats with advanced cirrhosis and ascites. Thus, jejunal structure and nutrient transport (D-galactose, L-leucine, L-proline, L-glutamic acid and L-cystine were studied in rats with ascitic cirrhosis. Methods Advanced cirrhosis was induced by CCl4 inhalation and Phenobarbital administration for 30 weeks. Cirrhotic animals were divided into two groups which received IGF-I or saline during two weeks. Control group was studied in parallel. Jejunal microvilli were studied by electron microscopy. Nutrient transport was assessed in brush border membrane vesicles using 14C or 35S-labelled subtracts in the three experimental groups. Results Intestinal active Na+-dependent transport was significantly reduced in untreated cirrhotic rats. Kinetic studies showed a decreased Vmax and a reduced affinity for sugar and four amino acids transporters (expressed as an increased Kt in the brush border membrane vesicles from untreated cirrhotic rats as compared with controls. Both parameters were normalised in the IGF-I-treated cirrhotic group. Electron microscopy showed elongation and fusion of microvilli with degenerative membrane lesions and/or notable atrophy. Conclusions The initial microvilli elongation reported in non ascitic cirrhosis develops into atrophy in rats with advanced cirrhosis and nutrient transports (monosaccharides and amino acids are progressively reduced. Both morphological and functional alterations improved significantly with low doses of IGF-I.

  11. Features of Hemodialysis in Cirrhotic Patients: Single Center Experience

    Directory of Open Access Journals (Sweden)

    Süleyman KÖZ

    2015-09-01

    Full Text Available OBJECTIVE: End-stage kidney disease and advanced cirrhosis are sometimes seen concomitantly. Our purpose was to compare hemodialysis (HD sessions in critically ill cirrhotic patients from ICU versus stable cirrhotic patients from outpatient clinic, and observe endurance of both stable and acutely ill cirrhotic patients to intermittent HD. MATERIAL and METHODS: All of the Child-Pugh class B or C cirrhotic patients requiring renal replacement therapy during a period of three years were included in the study. If hypotension, arrhythmia, bleeding, or any other health problems were present during dialysis, the dialysis session was regarded as a troubled session. RESULTS: There were two groups of patients. All of the stable patients lived more than three months, whereas all patients in the ICU group died within a month. Mean ultrafiltration volume per session was 1786±210 ml in ICU and 1616±266 ml in stable patients (p>0.05. The number of the troubled sessions was 24 in ICU and 1 in stable patients (p<0.0001. Bleeding was a problem in a minority of the patients. CONCLUSION: Intermittent HD may be an acceptable choice for stable cirrhotic dialysis patients. Hypotension is a frequent complication of intermittent HD in ICU patients.

  12. Platelet-activating factor in cirrhotic liver and hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Muriel Mathonnet; Bernard Descottes; Denis Valleix; Véronique Truffinet; Francois Labrousse; Yves Denizot

    2006-01-01

    AIM: Platelet-activating factor (PAF) is a pro-inflammatory and angiogenic lipid mediator. Here we aimed to investigate levels of PAF, lyso-PAF (the PAF precursor),phospholipase A2 (PLA2, the enzymatic activity generating lyso-PAF), acetylhydrolase activity (AHA, the PAF degrading enzyme) and PAF receptor (PAF-R) transcripts in cirrhotic liver and hepatocellular carcinoma (HCC).METHODS: Twenty-nine patients with HCC were ehrolled in this study. Cirrhosis was present in fourteen patients and seven had no liver disease. Tissue PAF levels were investigated by a platelet-aggregation assay. LysoPAF was assessed after its chemical acetylation into PAF.AHA was determined by degradation of [3H]-PAF. PLA2 levels were assessed by EIA. PAF-R transcripts were investigated using RT-PCR.RESULTS: Elevated amounts of PAF and PAF-R transcripts 1 (leukocyte-type) were found in cirrhotic tissues as compared with non-cirrhotic ones. Higher amounts of PAF and PAF-R transcripts 1 and 2 (tissue-type) were found in HCC tissues as compared with non-tumor tissues. PLA2, lyso-PAF and AHA levels were not changed in cirrhotic tissues and HCC.CONCLUSION: While the role of PAF is currently unknown in liver physiology, this study suggests its potential involvement in the inflammatory network found in the cirrhotic liver and in the angiogenic response during HCC.

  13. Changes of brain neuropeptide Y and its receptors in rats with flurazepam tolerance and dependence

    Institute of Scientific and Technical Information of China (English)

    Li-ping ZHANG; Li WANG

    2005-01-01

    Aim: Anticonvulsant tolerance and dependence are two obstacles that restrict the clinical use of benzodiazepines (BDZ). In order to explore the mechanism of these two adverse reactions, changes of neuropeptide Y (NPY) and its receptors in the hippocampus of rat models, in relation to flurazepam (FZP, a member of BDZ) tolerance and dependence, were investigated. Methods: The mRNA of preproNPY and its receptors (Y1, Y2, and Y5) in the hippocampus were determined by competitive RT-PCR, and the distribution of NPY in the hippocampus was examined by immunohistochemistry. Results: A decrease of preproNPY mRNA in the hippocampus was foundin tolerant and dependent rats. The level ofpreproNPY mRNA in the hippocampus was reversely correlated with the degree of tolerance and dependence, measured by the threshold of pentylenetetrazol-induced seizures.Immunohistochemistry indicated a decrease of NPY-immunoreactive material in neurons of the CA1, CA3, and dentate gyrus regions of both tolerant and dependent rats. The mRNA of NPY receptors Y1 and Y5 decreased in tolerant rats but did not change in dependent rats. The mRNA of NPY receptor Y2 increased in tolerant rats but decreased in dependent rats. Conclusion: A decrease of NPY in the hippocampus might be involved in anticonvulsant tolerance and dependence following long-term treatment with FZP. Y1, Y2, and Y5 mRNA were also altered in FZP tolerance and dependence.

  14. Epidermal growth factor in rat milk is dependent on insulin

    DEFF Research Database (Denmark)

    Thulesen, J; Poulsen, Steen Seier; Nexo, E;

    1993-01-01

    Epidermal growth factor (EGF) was measured in milk from four groups of rats: untreated diabetic, insulin-treated diabetic, insulin-treated normal and control rats. In the untreated diabetic group the volume of milk, and the concentration of EGF and the total output of EGF were significantly...... decreased when compared to the control group. In contrast, the total protein concentration in milk from the untreated diabetic rats was similar to the concentration in milk from the control rats. Insulin-treatment of diabetic rats almost completely reversed the decrease in the milk volume and in the...... concentration of EGF, and thus normalized the total output of EGF. The insulin-treated normal rats which remained euglycemic had a significantly increased concentration of EGF and of total protein without any difference in the volume of milk when compared to the controls. The results indicate that the secretion...

  15. Evaluation of cardiac functions of cirrhotic children using serum brain natriuretic peptide and tissue Doppler imaging

    OpenAIRE

    Aya M Fattouh; El-Shabrawi, Mortada H; Enas H Mahmoud; Wafaa O Ahmed

    2016-01-01

    Background: Cirrhotic cardiomyopathy (CCM) is described as the presence of cardiac dysfunction in cirrhotic patients. In children with chronic liver disease, CCM has been very rarely investigated. The Aim of the Study: Is to evaluate the cardiac function of cirrhotic children to identify those with CCM. Patients and Methods: Fifty-two cirrhotic patients and 53 age and sex matched controls were assessed using serum brain-type natriuretic peptide (BNP), conventional echocardiography, and tissue...

  16. [Surgical approach to posthepatitic cirrhotic patient today].

    Science.gov (United States)

    Meriggi, F; Forni, E

    1996-01-01

    A posthepatitic cirrhotic patient may undergo elective or urgent abdominal operation for an extra-hepatic or hepatic disease. According to the high postoperative morbidity (61%), surgery is indicated only for symptomatic or complicated cholelithiasis. A surgical procedure for refractory ascites has been devised to create a permanent peritoneo-venous shunt by a one way pressure-sensitive valve (Leveen). The procedure is simple and brings a long lasting relief with recovery in strength and nutrition and improved kidney function. Sclerotherapy is widely used to treat acute variceal bleeding while repeated sclerotherapy is used in the long-term management to eradicate varices. When indicated, liver transplantation is the best treatment to prevent variceal bleeding recurrence. Also portosystemic shunts effectively prevent recurrent variceal bleeding. They are, however, major operations with an important morbidity and mortality, particularly in poor risk patients. The most advocated shunts today are the Warren distal splenorenal shunt and the Sarfeh portacaval shunt using a small diameter prosthetic H-graft. The transjugular intrahepatic portosystemic stent-shunt (TIPSS) is a new treatment for portal hypertension and its complications. From a haemodynamic point of view it allows balanced hepatic perfusion. Postoperative mortality is rare; further bleeding and encephalopathy are reasonably acceptable. The most relevant complications concern dislocation of the prosthesis, stenosis and thrombosis of the shunt, which can be corrected by non-invasive dilatation. Encephalopathy is the main complication of surgical portosystemic shunts. It is usually controlled by protein diet restriction, and administration of lactulose or oral antibiotics. In severe forms the patients may be treated by an oesophageal transection with oesophagogastric devascularization, and by a postoperative suppression of the portosystemic shunt using external maneuvers. Posthepatitic liver cirrhosis is

  17. Endurance Training and Glutathione-Dependent Antioxidant Defense Mechanism in Heart of the Diabetic Rats

    OpenAIRE

    Mustafa Atalay; Osmo Hanninen; Mustafa Gul

    2003-01-01

    Regular physical exercise beneficially influences cardiac antioxidant defenses in normal rats. The aim of this study was to test whether endurance training can strengthen glutathione-dependent antioxidant defense mechanism and decrease lipid peroxidation in heart of the streptozotocin-induced diabetic rats. Redox status of glutathione in blood of diabetic rats in response to training and acute exercise was also examined. Eight weeks of treadmill training increased the endurance in streptozoto...

  18. Age-dependent effects of conditioning on cholinergic and vasopressin systems in the rat suprachiasmatic nucleus

    OpenAIRE

    Biemans, BAM; Van der Zee, EA; Daan, S.

    2003-01-01

    Active shock avoidance was used to explore the impact of behavioural stimulation on the neurochemistry of the suprachiasmatic nucleus. We have found previously that the expression of muscarinic acetylcholine receptors in the suprachiasmatic nucleus of young rats was significantly enhanced 24 hours after fear conditioning. Here, we investigated whether this observation is age-dependent. We used 26 month-old Wistar rats with a deteriorated circadian system, and compared them with young rats (4 ...

  19. Age-dependent seizures of absence epilepsy and sleep spindles dynamics in WAG/Rij rats

    Science.gov (United States)

    Grubov, Vadim V.; Sitnikova, Evgenia Y.; Pavlov, Alexey N.; Khramova, Marina V.; Koronovskii, Alexey A.; Hramov, Alexander E.

    2015-03-01

    In the given paper, a relation between time-frequency characteristics of sleep spindles and the age-dependent epileptic activity in WAG/Rij rats is discussed. Analysis of sleep spindles based on the continuous wavelet transform is performed for rats of different ages. It is shown that the epileptic activity affects the time-frequency intrinsic dynamics of sleep spindles.

  20. Spermidine-Induced Improvement of Reconsolidation of Memory Involves Calcium-Dependent Protein Kinase in Rats

    Science.gov (United States)

    Girardi, Bruna Amanda; Ribeiro, Daniela Aymone; Signor, Cristiane; Muller, Michele; Gais, Mayara Ana; Mello, Carlos Fernando; Rubin, Maribel Antonello

    2016-01-01

    In this study, we determined whether the calcium-dependent protein kinase (PKC) signaling pathway is involved in the improvement of fear memory reconsolidation induced by the intrahippocampal administration of spermidine in rats. Male Wistar rats were trained in a fear conditioning apparatus using a 0.4-mA footshock as an unconditioned stimulus.…

  1. Hepatocellular carcinoma (HCC) in non-cirrhotic liver: clinical, radiological and pathological findings

    Energy Technology Data Exchange (ETDEWEB)

    Di Martino, Michele; Di Miscio, Rossella; Lombardo, Concetta Valentina; Catalano, Carlo [University of Rome ' ' Sapienza' ' , Department of Radiological Sciences, Oncology and Anatomical Pathology, Rome (Italy); Saba, Luca; Piga, Mario [Department of Radiology Azienda Ospedaliera Universitaria (A.O.U.), Monserrato (Italy); Bosco, Sandro [University of Rome ' ' Sapienza' ' , Department of Molecular Medicine, Rome (Italy); Rossi, Massimo [University of Rome ' ' Sapienza' ' , Department of General Surgery, Division of Organ Transplantation, Rome (Italy); Miles, Kirchin A. [Worldwide Medical and Regulatory Affairs, Milan (Italy); Tamponi, Elisabetta [Azienda Ospedaliera Universitaria (A.O.U.), Department of Anatomical Pathology, Monserrato (Italy)

    2014-07-15

    Our aim was to evaluate the clinical and pathological findings, mutidetector-row computed tomography (MDCT) and magnetic resonance imaging (MRI) appearances, treatment and 1-year survival of patients with HCC in non-cirrhotic liver. Histopathological and laboratory findings of 30 non-cirrhotic patients with 32 HCCs were reviewed retrospectively. MDCT and gadobenate dimeglumine-enhanced MR images were evaluated in consensus by two radiologists in terms of HCC size, presence of tumour capsule, necrosis, haemorrhage, fat and calcification, and vascular involvement. Imaging patterns were compared directly with HCC findings in a matched group of cirrhotic patients. No differences between non-cirrhotic and cirrhotic patients were noted in terms of serum α-fetoprotein levels (elevated in 11 [36.7 %] and 21 [35 %] patients, respectively). The imaging appearance at CT and contrast-enhanced MRI was typical in 27 (84.3 %) and 28 (87.5 %) cases respectively. Most lesions presented as a well-differentiated large solitary mass, with well-defined margins, areas of necrosis and peripheral capsule. No significant differences in HCC pattern were observed between cirrhotic and non-cirrhotic liver. In non-cirrhotic patients, HCC is more likely to manifest as an asymptomatic mass with elevation of serum tumour markers similar to that seen in cirrhotic patients. HCC in cirrhotic and non-cirrhotic livers show similar enhancement patterns. (orig.)

  2. The hyperinsulinemia produced by concanavalin A in rats is opioid-dependent and hormonally regulated

    OpenAIRE

    J. Francisco-DoPrado; J.E. Zambelli; M.H. Melo-Lima; G. Ribeiro-DaSilva

    1998-01-01

    The present study examines the effect of concanavalin A (Con A) on the blood insulin and glucose levels of rats. Male and female rats treated with Con A (62.5-500 µg/kg) for three days showed a dose- and time-dependent hyperinsulinemia that lasted more than 48 h. Male rats were more sensitive to Con A. Thus, 6 h after treatment with Con A the circulating insulin levels in male rats had increased by 85% (control: 10.2 ± 0.9 mU/l and Con A-treated: 18.8 ± 1 mU/l) compared to only 38% (control: ...

  3. Omega-3 polyunsaturated fatty acids prevent progression of liver fibrosis and promote liver regeneration after partial hepatectomy in cirrhotic rats%ω-3多不饱和脂肪酸对肝硬化大鼠肝切除术后肝细胞再生及肝纤维化程度的影响

    Institute of Scientific and Technical Information of China (English)

    杨跃; 段飞; 蔡浩; 陈靓; 林建宇; 仇毓东

    2013-01-01

    Objective:To evaluate the effect of omega-3 polyunsaturated fatty acids (ω-3 PUFA) on liver regeneration after hepatectomy and antifibrosis under the condition of liver cirrhosis in rats. Methods:Seventy precent hepatectomy was carried out in rats,which were subsequently divided into 4 groups: ①normal and hepatectomy group(PH) ,②liver cirrhosis and hepatectomy group(LC + PH) , ③liver cirrhosis,n-3 PUFA (1 ml/kg) and hepatectomy group (LC +n-3 PUFA[S] +PH) ,④liver cirrhosis , n-3 PUFA (2 ml/kg) and hepatectomy group (LC + n-3PUFA[ L] + PH). Body/liver weight ratios , Serum parameters, histopathological examination, immunostaining and quantification of mRNA expression were also investigated. Results:Liver regeneration in LC + PH group was significantly delayed compared with PH group 7 days after hepatectomy. On the other hand,liver regeneration in LC + n-3 PUFA[L] +PH group increased significantly. The liver fibrosis was significantly lower in the groups with use of n-3 PUFA. Conclusion: The n-3 PUFA can reduce liver fibrosis and promote liver regeneration, even under cirrhotic conditions.%目的:观察ω-3多不饱和脂肪酸(ω-3PUFA)对肝硬化大鼠70%肝切除术后肝细胞再生及肝纤维化程度的影响. 方法:将96只大鼠随机分为四组,即正常对照组(仅行70%肝切除);肝硬化对照组(肝硬化大鼠行70%肝切除);肝硬化小剂量组(肝硬化大鼠行70%肝切除后静脉注射ω-3PUFA 1 ml/kg);肝硬化大剂量组(肝硬化大鼠行70%肝切除后静脉注射ω-3PUFA 2 ml/kg).观察大鼠术后第1、3、5和7天肝细胞再生的情况,肝功能指标,残肝肝纤维化程度的变化等. 结果:与肝硬化对照组比,肝硬化大剂量组大鼠术后肝有明显的再生(P<0.05);术后第1和第3天ALT和AST有明显降低(P<0.05).术后第7天,肝硬化小剂量组和肝硬化大剂量组肝纤维化程度有明显减轻(P<0.05). 结论:ω-3PUFA不仅能促进肝硬化大鼠术后肝细胞再

  4. Myoelectric activity of the small intestine during morphine dependence and withdrawal in rats

    Energy Technology Data Exchange (ETDEWEB)

    Kuperman, D.A.; Sninsky, C.A.; Lynch, D.F.

    1987-04-01

    The authors investigated (1) the effect of morphine dependence on the migrating myoelectric complex (MMC) of the small intestine, (2) whether bacterial overgrowth developed in morphine-dependent rats, and (3) the effect of naloxone and methylbromide naltrexone, a peripheral opioid antagonist, on the MMC in morphine-naive and morphine-dependent rats. They also evaluated intestinal motility during naloxone-induced withdrawal in animals pretreated with clonidine. Intestinal myoelectric activity was monitored by four indwelling electrodes in unanesthetized, fasted rats. D-(/sup 14/C)xylose breath tests were performed before and after morphine-pellet implantation to evaluate the presence of bacterial overgrowth of the small intestine. Naloxone had no effect on myoelectric activity of the small intestine in morphine-naive rats. Cycling activity fronts were present in morphine-dependent animals, but there was a significant prolongation of activity front periodicity and slowing of the propagation velocity. No significant increase in /sup 14/CO/sub 2/ excretion was noted in the morphine-dependent rats. They conclude from their studies that (1) myoelectric activity of the small intestine develops incomplete tolerance to morphine; (2) bacterial overgrowth is not a feature of morphine dependence in the rat; (3) alterations of intestinal myoelectric activity are a component of the opiate withdrawal syndrome, and they appear at least partially mediated by a peripheral mechanism that can be suppressed by an ..cap alpha../sub 2/-adrenergic agonist.

  5. Change of Cystine/Glutamate Antiporter Expression in Ethanol-Dependent Rats

    Directory of Open Access Journals (Sweden)

    Alessandra Tiziana Peana

    2014-10-01

    Full Text Available Background: Some drugs of abuse down regulate the expression of cystine/glutamate (xCT antiporter in the nucleus accumbens (Acb after extinction or withdrawal. The altered level of xCT exchanger in Acb, a structure involved in ethanol reinforcement, may contribute to the pathological glutamatergic signalling, linked to addiction. We hypothesised that the expression of xCT may be changed in Acb and whole brain also in non-dependent (occasional drinkers, ethanol-dependent rats, as well as, during ethanol withdrawal.Methods: Wistar rats were made ethanol-dependent by chronic exposure to an alcoholic milk beverage (from 2.4 to 7.2% v/v ethanol. Ethanol non-dependent rats were exposed to a similar, but non-alcoholic liquid diet and self-administered ethanol (10% twice a week. Withdrawal in ethanol-dependent rats was studied at 12 hours after the last ethanol-enriched diet exposure. Immediately after the measurement of somatic signs of withdrawal, Western blot analysis with a polyclonal antibody against xCT was carried out in a naïve control group, non-dependent and ethanol-dependent rats as well as withdrawal rats, in order to study the level of xCT expression in Acb and whole brain. Results. Non-dependent rats self-administered an average dose of 1.21±0.02 g/kg per session (30 min. Daily ethanol consumption during chronic exposure to the alcoholic beverage ranged from 6.30±0.16 to 13.99±0.66 g/kg. Ethanol dependent rats after suspension of the ethanol-enriched diet have shown significant somatic signs of withdrawal. Western blotting analysis of Acb lysates revealed that xCT was over expressed in ethanol-dependent rats whereas in whole brain preparations xCT was over expressed in both non-dependent and ethanol-dependent rats compared to control group. On the contrary, xCT expression during withdrawal was down regulated in Acb and restored to control level in whole brain preparations. Conclusions: The changes of xCT expression in both Acb and

  6. Quantitative Proteomic Profiling of Muscle Type-Dependent and Age-Dependent Protein Carbonylation in Rat Skeletal Muscle Mitochondria

    OpenAIRE

    Feng, Juan; Xie, Hongwei; Meany, Danni L.; Thompson, LaDora V.; Arriaga, Edgar A.; Griffin, Timothy J.

    2008-01-01

    Carbonylation is a highly prevalent protein modification in skeletal muscle mitochondria, possibly contributing to its functional decline with age. Using quantitative proteomics, we identified mitochondrial proteins susceptible to carbonylation in a muscle type (slow- vs fast-twitch)-dependent and age-dependent manner from Fischer 344 rat skeletal muscle. Fast-twitch muscle contained twice as many carbonylated mitochondrial proteins than did slow-twitch muscle, with 22 proteins showing signif...

  7. Ferritin-dependent radical generation in rat liver homogenates

    International Nuclear Information System (INIS)

    The hypothesis of this study was that mammalian ferritin (FER) has the ability of releasing Fe in the tissue to catalyze the generation of free radicals, such as ascorbyl (A·) and hydroxyl radical (·OH), that might lead to the damage of FER itself. The rat liver homogenates exhibited an electron paramagnetic resonance (EPR) signal with the spectral features (aH = 1.88 G, g = 2.0054) of A·. The addition to the reaction medium of isolated rat liver FER increased by 3-fold the EPR signal, as compared to the recorded value in its absence. Isolated microsomes from rat liver incubated during 10 min showed a signal with the spectral features (aH = 15 G, g = 2.0062) of ·OH. The addition of FER in the presence of either ethylenediamine-tetraacetic acid (EDTA) or adenosine-5'-triphosphate (ATP) significantly increased the recorded spectra. The labile Fe pool (LIP) in the homogenate was assessed by EPR. The rat liver homogenates exhibited an EPR signal with the spectral features (g = 4.3) of the Fe2+ and was significantly increased by the addition of FER (3-fold). The oxidation profile of the isolated FER from rat liver was analyzed after incubation with 10 mM ascorbate (AH-). A drastic increase in the width of the band suggested alterations to the protein structure. The FER content of tryptophan (Trp) and thiols was significantly lower when the incubation was performed in the presence of AH- as compared to the recorded effect in its absence. The data in tissue homogenates presented here showed that radical generation is associated to FER Fe release, and moreover that the FER protein itself was affected during this process.

  8. Short term cadmium administration dose dependently elicits immediate biochemical, neurochemical and neurobehavioral dysfunction in male rats.

    Science.gov (United States)

    Haider, Saida; Anis, Lubna; Batool, Zehra; Sajid, Irfan; Naqvi, Fizza; Khaliq, Saima; Ahmed, Shoaib

    2015-02-01

    Cadmium is a toxic environmental and industrial pollutant. Cadmium toxicity has been reported to produce biochemical and behavioral dysfunction that may cause adverse effects on several organs including the central nervous system. The present study was designed to investigate the neurotoxic effects of Cadmium Chloride (CdCl2) at three different doses by using different behavioral models. Lipid peroxidation (LPO), superoxide dismutase (SOD) and acetylcholinesterase (AChE) activities were also monitored following acute intraperitoneal injection of cadmium. Twenty four adult locally bred Albino Wistar rats were divided into control and 3 test groups (n = 6). Control rats were injected intraperitoneally with saline (0.9% NaCl) and test groups were injected with CdCl2 (1 mg/kg, 2 mg/kg and 3 mg/kg) dissolved in physiological solution. Behavioral activities of rats were monitored after 1 h of cadmium injection. Locomotor activity and depression-like symptoms were measured by Open Field Test (OFT) and Forced Swimming Test (FST) respectively. Anxiety like behavior was monitored using Light-dark Transition (LDT) test and memory functions of rats were assessed by Morris Water Maze test (MWM). In the present study acute cadmium administration dose dependently increased anxiety in rats as compared to control rats. A significant increase in depression-like symptoms was also exhibited by cadmium treated rats. These behavioral dysfunctions may be attributed to the decreased superoxide dismutase (SOD) activity and simultaneously increased brain lipid peroxidation (LPO). Moreover learning and memory assessed by MWM showed dose dependent impairment in memory function in cadmium treated rats as compared to control rats. Acetylcholinesterase (AChE) activity was also decreased in brains of cadmium administered rats. It is suggested in this study that behavioral, biochemical and neurochemical dysfunctions caused by acute cadmium administration occur in a dose dependent manner.

  9. Prevalence of subclinical hepatic encephalopathy in cirrhotic patients in China

    Institute of Scientific and Technical Information of China (English)

    Yu-Yuan Li; Yu-Qiang Nie; Wei-Hong Sha; Zheng Zeng; Fu-Ying Yang; Li Ping; Lin Jia

    2004-01-01

    AIM: Subclinical hepatic encephalopathy (SHE) is a common complication of liver diseases. The aim of this study was to find out the normal value of psychometric test and to investigate the prevalence of SHE in Chinese patients with stabilized hepatic cirrhosis.METHODS: Four hundred and nine consecutive cirrhotic patients without overt clinical encephalopathy were screened for SHE by using number connection test part A (NCT-A) and symbol digit test (SDT). SHE was defined as presence of at least one abnormal psychometric test. The age-corrected normal values were defined as the mean±2times standard deviation (2SD), and developed in 356 healthy persons as normal controls. Four hundred and sixteen patients with chronic viral hepatitis were tested as negative controls to assess the diagnostic validity of this test battery.RESULTS: There was no significant difference in NCT scores and SDT quotients between healthy controls and chronic hepatitis group (P>0.05). In all age subgroups,the NCT and SDT measurements of cirrhotic patients differed significantly from those of the controls (P<0.05).When mean±2SD of SDT and NCT measurements from healthy control group was set as the normal range, 119cirrhotic patients (29.1%) were found to have abnormal NCT-A and SDT tests, 53 (13.0%) were abnormal only in SDT and 36 (8.8%) only in NCT-A. Taken together, SHE was diagnosed in 208 (50.9%) cirrhotic patients by this test battery. The prevalence of SHE increased from 39.9%and 55.2% in Child-Pugh's grade A and B groups to 71.8%in Child-Pugh's grade C group (P<0.05). After the adjustment of age and residential areas required from the tests, no correlation was found in the rate of SHE and causes of cirrhosis, education level and smoking habit.CONCLUSION: Psychometric tests are simple and reliable indicators for screening SHE among Chinese cirrhotic patients. By using a NCT and SDT battery, SHE could be found in 50.9% of cirrhotic patients without overt clinical encephalopathy. The

  10. Age dependency of vasopressin pulmonary vasodilatory effect in rats

    OpenAIRE

    Enomoto, Masahiro; Pan, Jingyi; Shifrin, Yulia; Belik, Jaques

    2013-01-01

    Background Vasopressin is a systemic vasoconstrictor. Its pulmonary vasodilatory effect is controversial and limited data are available on its use in neonates with pulmonary hypertension. Hypothesizing that the vasopressin-induced pulmonary vasodilation is developmentally regulated, we evaluated its pulmonary and systemic arterial response in newborn and adult rats. Methods Vessels were mounted on a wire myograph and the vasopressin-induced changes in vasomotor tone measured. The vessel- and ...

  11. Effects of morphine dependence and withdrawal on levels of neurosteroids in rat brain

    Institute of Scientific and Technical Information of China (English)

    Cai-zhen YAN; Yan-ning HOU

    2004-01-01

    AIM: To investigate the effects of morphine dependence and withdrawal on the concentrations of neurosteroids in rat brain. METHODS: A method of simultaneous quantification of neurosteroids by gas chromatography-mass spectrometry (GC-MS) had been established. RESULTS: The chronic morphine administration (ip) resulted in a marked decrease in the brain concentrations of pregnenolone (PREG), progesterone (PROG), and pregenenolone sulfate (PREGS) in rats killed 6 h after the last treatment. In contrast, there were no significant effects of morphine dependence on the brain concentrations of allopregnanolone (AP), dihydroepiandrosterone (DHEA), and dihydroepiandrosterone sulfate (DHEAS). Naloxone-induced withdrawal produced a significant increase in the concentrations of PREG, PROG, AP, DHEA, PREGS, and DHEAS as compared with the control group.CONCLUSION: Morphine dependence and withdrawal affected the concentrations of neurosteroids in rat brain,which suggests that endogenous neurosteroids in brain might be related to the development of morphine dependence and withdrawal.

  12. [Activity of Ca(2+)-dependent neutral proteinases in rat organs under cobalt and mercury chloride injection].

    Science.gov (United States)

    Kaliman, P A; Samokhin, A A; Samokhina, L M

    2003-01-01

    The activity of Ca(2+)-dependent neutral proteinases in rats under cobalt and mercury chloride injection was investigated. The calpains activity increase in the lungs, heart, liver and kidneys was revealed after 2 h cobalt chloride action. The mercury chloride gives a reliable increase of calcium-dependent neutral proteinases only in the kidneys. PMID:14574747

  13. The role of basolateral amygdala adrenergic receptors in hippocampus dependent spatial memory in rat

    OpenAIRE

    Vafaei A.L.; Rashidy-Pour A

    2008-01-01

    Background and the purpose of the study: There are extensive evidences indicating that the noradrenergic system of the basolateral nucleus of the amygdala (BLA) is involved in memory processes. The present study investigated the role of the BLA adrenergic receptors (ARs) in hippocampus dependent spatial memory in place avoidance task in male rat. Material and Methods: Long Evans rats (n=150) were trained to avoid footshock in a 60° segment while foraging for scattered food on a circul...

  14. Free radical activity during development of insulin-dependent diabetes mellitus in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Pitkaenen, O.M.; Akerblom, H.K.; Sariola, H.; Andersson, S.M. (Univ. of Helsinki (Finland)); Martin, J.M. (Hospital for Sick Children, Toronto, Ontario (Canada)); Hallman, M. (Univ. of California, Irvine (United States))

    1991-01-01

    Free radical-induced lipid peroxidation was quantified by measuring expired pentane from diabetic prone BB Wistar rats of 45-90 d of age. Insulin-dependent diabetes mellitus was manifest at the age of 71 {plus minus} 8 d. Expired pentane increased from 2.1 {plus minus} 0.7 to 5.0 {plus minus}3.0 pmol/100g/min (p <0.01) at manifestation of the disease and remained high throughout the test period. In healthy age-matched control rats it persisted low. In rats made diabetic with streptozotocin, expired pentane remained low. The changes in expired pentane suggest that the development of endogenous insulin-dependent diabetes mellitus in BB rats is associated with increased free radical activity. This is not due to hyperglycemia or ketosis per se, and reflects a fundamental difference in the free radical activity between the spontaneously diabetic BB rats and the disease produced by streptozotocin. Development of spontaneous insulin-dependent diabetes in BB rats is associated with increased free radical activity that persists after the manifestation of the disease.

  15. Effects of cyclooxygenase-2 on sinusoidal capillarization in cirrhotic rats induced by carbon tetrachloride%环氧合酶-2在四氯化碳诱导肝硬化大鼠肝窦毛细血管化形成中的作用

    Institute of Scientific and Technical Information of China (English)

    涂传涛; 王吉耀; 郭津生

    2009-01-01

    目的 观察环氧合酶-2(COX-2)在实验性肝硬化大鼠肝窦毛细血管化形成中的作用.方法 腹腔注射CCl4每周2次共8周诱导雄性SD大鼠肝硬化模型.将SD大鼠分成3组:正常对照组(n=10)、模型对照组(n=15)和罗非昔布治疗组(10 mg·kg-1·d-1,n=15).光镜下观察肝组织标本,电镜观察肝窦超微结构改变.用Western印迹和免疫组化法检测基底膜蛋白主要成分层粘连蛋白(LN)和Ⅳ型胶原,同时通过Ⅷ因子相关抗原(vWF)免疫组化标记微血管牛成密度.结果 与模型对照组相比,罗非昔布干预治疗能减少肝纤维化面积(分别为30.7±8.9和23.5±6.5,P<0.05).光镜及电镜提示,在模型对照组可见肝窦内皮细胞窗孔减少、缩小,有完整的基底膜形成,Disse腔隙内有大量的胶原纤维沉积,罗非昔布组上述病变有所减轻.随着肝硬化的形成,肝组织微血管密度明显升高,罗非昔布组肝组织微血管密度(6.4±0.7)较模型对照组(11.3±1.6)明显降低(P<0.01).肝硬化时肝组织表达Ⅳ型胶原和LN蛋白明显增加(分别为3.8±0.4和3.7±0.5),罗非昔布能降低Ⅳ犁胶原和LN的表达(分别为3.0±0.5和3.0±0.5;与模型对照组相比两者均为Pcirrhotic rats. Methods The SD rats were intraperitoneally injected with carbon tetrachloride (CCl4) twice a week for 8 weeks to induce liver cirrhosis. The rats were randomly divided into three groups: normal control group (n= 10), model control group (n= 15) and rofecoxib treated group (received 10 mg/kg of rofecoxib daily, n = 15). Liver histopathology was examined by light microscopy, and sinusoidal ultrastructure was observed by transmission electron microscopy. Furthermore, the level of basement membrane proteins (collagen type

  16. Pubertal dependent effects of cadmium on episodic prolactin secretion in male rats

    Energy Technology Data Exchange (ETDEWEB)

    Lafuente, A.; Alvarez-Demanuel, E.; Marquez, N. [Fac. de Cienicas, Orense (Spain). Lab. de Toxicologia; Esquifino, A.I. [Dept. Bioquimica, Facultad de Medicina, Universidad Complutense, 28040-Madrid (Spain)

    1999-02-01

    This work was undertaken to assess if exposure to cadmium related to puberty may affect the episodic pattern of prolactin. Male rats were submitted to cadmium exposure, from day 30 to 60 or from day 60 to 90 of life respectively, at a dose of 50 ppm in the drinking water. Control age-matched rats received cadmium-free water. Prepubertal cadmium administration decreased mean serum prolactin levels and the absolute amplitude of the prolactin pulses. Subchronic exposure to cadmium of adult rats decreased mean serum prolactin levels, the absolute amplitude of the prolactin pulses and their duration, and the mean half-life of the hormone. These results suggest that subchronic cadmium exposure changes the secretory pattern of prolactin in adult male rats in a puberty-dependent way. (orig.) With 1 fig., 1 tab., 37 refs.

  17. Fluoxetine exerts age-dependent effects on behavior and amygdala neuroplasticity in the rat.

    Directory of Open Access Journals (Sweden)

    Judith R Homberg

    Full Text Available The selective serotonin reuptake inhibitor (SSRI Prozac® (fluoxetine is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby may have harmful effects in adolescents. Here we treated adolescent and adult rats chronically with fluoxetine (12 mg/kg at postnatal day (PND 25 to 46 and from PND 67 to 88, respectively, and tested the animals 7-14 days after the last injection when (norfluoxetine in blood plasma had been washed out, as determined by HPLC. Plasma (norfluoxetine levels were also measured 5 hrs after the last fluoxetine injection, and matched clinical levels. Adolescent rats displayed increased behavioral despair in the forced swim test, which was not seen in adult fluoxetine treated rats. In addition, beneficial effects of fluoxetine on wakefulness as measured by electroencephalography in adults was not seen in adolescent rats, and age-dependent effects on the acoustic startle response and prepulse inhibition were observed. On the other hand, adolescent rats showed resilience to the anorexic effects of fluoxetine. Exploratory behavior in the open field test was not affected by fluoxetine treatment, but anxiety levels in the elevated plus maze test were increased in both adolescent and adult fluoxetine treated rats. Finally, in the amygdala, but not the dorsal raphe nucleus and medial prefrontal cortex, the number of PSA-NCAM (marker for synaptic remodeling immunoreactive neurons was increased in adolescent rats, and decreased in adult rats, as a consequence of chronic fluoxetine treatment. No fluoxetine-induced changes in 5-HT(1A receptor immunoreactivity were observed. In conclusion, we show that fluoxetine exerts both harmful and beneficial age-dependent effects on depressive behavior, body weight and wakefulness, which may relate, in part, to differential

  18. Ursodeoxycholic Acid Influences the Expression of p27kip1 but Not FoxO1 in Patients with Non-Cirrhotic Primary Biliary Cirrhosis

    Directory of Open Access Journals (Sweden)

    Malgorzata Milkiewicz

    2014-01-01

    Full Text Available Background. Enhanced expression of cell cycle inhibitor p27kip1 suppresses cell proliferation. Ursodeoxycholic acid (UDCA delays progression of primary biliary cirrhosis (PBC but its effect on p27kip1 expression is uncertain. Aims. To analyze the expression of p27kip1 and its transcription modulator FoxO1 in patients with PBC, and to assess the impact of UDCA on this pathway. Materials and Methods. The examined human tissue included explanted livers from patients with cirrhotic PBC (n=23, primary sclerosing cholangitis (PSC; n=9, alcoholic liver disease (ALD; n=9, and routine liver biopsies from patients with non-cirrhotic PBC (n=26. Healthy liver samples served as controls (n=19. Livers of FoxO-deficient mice were also studied. mRNA and protein expressions were analyzed by real-time PCR and Western blot. Results. p27kip1 expression was increased in cirrhotic and non-cirrhotic PBC. FoxO1 mRNA levels were increased in PBC (8.5-fold increase versus controls. FoxO1 protein expression in PBC was comparable to controls, but it was decreased in patients with PSC and ALD (63% and 70% reduction, respectively; both P<0.05 versus control. UDCA-treated non-cirrhotic patients with PBC showed decreased expression of p27kip1 mRNA. Conclusion. PBC progression is characterized by a FoxO1-independent increase of p27kip1 expression. In early PBC, UDCA may enhance liver regeneration via p27kip1-dependent mechanism.

  19. The hyperinsulinemia produced by concanavalin A in rats is opioid-dependent and hormonally regulated

    Directory of Open Access Journals (Sweden)

    J. Francisco-DoPrado

    1998-05-01

    Full Text Available The present study examines the effect of concanavalin A (Con A on the blood insulin and glucose levels of rats. Male and female rats treated with Con A (62.5-500 µg/kg for three days showed a dose- and time-dependent hyperinsulinemia that lasted more than 48 h. Male rats were more sensitive to Con A. Thus, 6 h after treatment with Con A the circulating insulin levels in male rats had increased by 85% (control: 10.2 ± 0.9 mU/l and Con A-treated: 18.8 ± 1 mU/l compared to only 38% (control: 7.5 ± 0.2 mU/l; Con A-treated: 10.3 ± 0.9 mU/l in females. An identical response was seen after 12 h. Con A (250 µg/kg produced time-dependent hypoglycemia in both sexes but more pronounced in males. There was no correlation between the hypoglycemia and hyperinsulinemia described above. The Con A-induced hyperinsulinemia in rats of both sexes was abolished in gonadectomized animals (intact males: +101 ± 17% vs orchiectomized males: -5 ± 3%; intact females: +86 ± 23% vs ovariectomized females: -18 ± 7.2%. Pretreating intact male and female rats with human chorionic gonadotropin also significantly inhibited the Con A-induced hyperinsulinemia. Estradiol (10 µg/kg, im significantly blocked the Con A-induced increase in circulating insulin in male rats (101 ± 17% for controls vs 32 ± 5.3% for estradiol-treated animals, P<0.05 while testosterone (10 mg/kg, im had no similar effect on intact female rats. Pretreating Con A-injected rats with opioid antagonists such as naloxone (1 mg/kg, sc and naltrexone (5 mg/kg, sc blocked the hyperinsulinemia produced by the lectin in males (control: +101 ± 17% vs naloxone-treated: +5 ± 14%, or naltrexone-treated: -23 ± 4.5% and females (control: +86 ± 23% vs naloxone-treated: +21 ± 20%, or naltrexone-treated: -18 ± 11%. These results demonstrate that Con A increases the levels of circulating insulin in rats and that this response is opioid-dependent and hormonally regulated.

  20. The hyperinsulinemia produced by concanavalin A in rats is opioid-dependent and hormonally regulated.

    Science.gov (United States)

    Francisco-DoPrado, J; Zambelli, J E; Melo-Lima, M H; Ribeiro-DaSilva, G

    1998-05-01

    The present study examines the effect of concanavalin A (Con A) on the blood insulin and glucose levels of rats. Male and female rats treated with Con A (62.5-500 micrograms/kg) for three days showed a dose- and time-dependent hyperinsulinemia that lasted more than 48 h. Male rats were more sensitive to Con A. Thus, 6 h after treatment with Con A the circulating insulin levels in male rats had increased by 85% (control: 10.2 +/- 0.9 mU/l and Con A-treated: 18.8 +/- 1 mU/l) compared to only 38% (control: 7.5 +/- 0.2 mU/l; Con A-treated: 10.3 +/- mU/l) in females. An identical response was seen after 12 h. Con A (250 micrograms/kg) produced time-dependent hypoglycemia in both sexes but more pronounced in males. There was no correlation between the hypoglycemia and hyperinsulinemia described above. The Con A-induced hyperinsulinemia in rats of both sexes was abolished in gonadectomized animals (intact males: +101 +/- 17% vs orchiectomized males: -5 +/- 3%; intact females: +86 +/- 23% vs ovariectomized females: -18 +/- 7.2%). Pretreating intact male and female rats with human chorionic gonadotropin also significantly inhibited the Con A-induced hyperinsulinemia. Estradiol (10 micrograms/kg,i.m.) significantly blocked the Con A-induced increase in circulating insulin in male rats (101 +/- 17% for controls vs 32 +/- 5.3% for estradiol-treated animals, P testosterone (10 mg/kg, i.m.) had no similar effect on intact female rats. Pretreating Con A-injected rats with opioid antagonists such as naloxone (1 mg/kg, s.c.) and naltrexone (5 mg/kg, s.c.) blocked the hyperinsulinemia produced by the lectin in males (control: +101 +/- 17% vs naloxone-treated: +5 +/- 14%, or naltrexone-treated: -23 +/- 4.5%) and females (control: +86 +/- 23% vs naloxone-treated: +21 +/- 20%, or naltrexone-treated: -18 +/- 11%). These results demonstrate that Con A increases the levels of circulating insulin in rats and that this response is opioid-dependent and hormonally regulated. PMID:9698777

  1. The incidence of venous thromboembolism and practice of deep venous thrombosis prophylaxis in hospitalized cirrhotic patients

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    Alqahtani Saad

    2011-01-01

    Full Text Available Abstract Background Cirrhotic patients are characterized by a decreased synthesis of coagulation and anticoagulation factors. The coagulopathy of cirrhotic patients is considered to be auto-anticoagulation. Our aim was to determine the incidence and predictors of venous thromboembolism (VTE and examine the practice of deep venous thrombosis (DVT prophylaxis among hospitalized cirrhotic patients. Methods A retrospective cohort study was performed in a tertiary teaching hospital. We included all adult patients admitted to the hospital with a diagnosis of liver cirrhosis from January 1, 2009 to December 31, 2009. We grouped our cohort patients in two groups, cirrhotic patients without VTE and cirrhotic with VTE. Results Over one year, we included 226 cirrhotic patients, and the characteristics of both groups were similar regarding their clinical and laboratory parameters and their outcomes. Six patients (2.7% developed VTE, and all of the VTEs were DVT. Hepatitis C was the most common (51% underlying cause of liver cirrhosis, followed by hepatitis B (22%; 76% of the cirrhotic patients received neither pharmacological nor mechanical DVT prophylaxis. Conclusion Cirrhotic patients are at risk for developing VTE. The utilization of DVT prophylaxis was suboptimal.

  2. The diminished expression of proangiogenic growth factors and their receptors in gastric ulcers of cirrhotic patients.

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    Jiing-Chyuan Luo

    Full Text Available OBJECTIVES: The pathogenesis of the higher occurrence of peptic ulcer disease in cirrhotic patients is complex. Platelets can stimulate angiogenesis and promote gastric ulcer healing. We compared the expressions of proangiogenic growth factors and their receptors in the gastric ulcer margin between cirrhotic patients with thrombocytopenia and those of non-cirrhotic patients to elucidate possible mechanisms. METHODS: Eligible cirrhotic patients (n = 55 and non-cirrhotic patients (n = 55 who had gastric ulcers were enrolled. Mucosa from the gastric ulcer margin and non-ulcer areas were sampled and the mRNA expressions of the proangiogenic growth factors (vascular endothelial growth factor [VEGF], platelet derived growth factor [PDGF], basic fibroblast growth factor [bFGF] and their receptors (VEGFR1, VEGFR2, PDGFRA, PDGFRB, FGFR1, FGFR2 were measured and compared. Platelet count and the expressions of these growth factors and their receptors were correlated with each other. RESULTS: The two groups were comparable in terms of gender, ulcer size and infection rate of Helicobacter pylori. However, the cirrhotic group were younger in age, had a lower platelet count than those in the non-cirrhotic group (p0.5, p<0.001. CONCLUSIONS: Our findings implied that diminished activity of proangiogenic factors and their receptors may contribute to the pathogenesis of gastric ulcers in cirrhotic patients.

  3. Diagnostic non-invasive model of large risky esophageal varices in cirrhotic hepatitis C virus patients

    Science.gov (United States)

    Elalfy, Hatem; Elsherbiny, Walid; Abdel Rahman, Ashraf; Elhammady, Dina; Shaltout, Shaker Wagih; Elsamanoudy, Ayman Z; El Deek, Bassem

    2016-01-01

    AIM To build a diagnostic non-invasive model for screening of large varices in cirrhotic hepatitis C virus (HCV) patients. METHODS This study was conducted on 124 post-HCV cirrhotic patients presenting to the clinics of the Endemic Medicine Department at Mansoura University Hospital for evaluation before HCV antiviral therapy: 78 were Child A and 46 were Child B (score ≤ 8). Inclusion criteria for patients enrolled in this study was presence of cirrhotic HCV (diagnosed by either biopsy or fulfillment of clinical basis). Exclusion criteria consisted of patients with other etiologies of liver cirrhosis, e.g., hepatitis B virus and patients with high MELD score on transplant list. All patients were subjected to full medical record, full basic investigations, endoscopy, and computed tomography (CT), and then divided into groups with no varices, small varices, or large risky varices. In addition, values of Fibrosis-4 score (FIB-4), aminotransferase-to-platelet ratio index (APRI), and platelet count/splenic diameter ratio (PC/SD) were also calculated. RESULTS Detection of large varies is a multi-factorial process, affected by many variables. Choosing binary logistic regression, dependent factors were either large or small varices while independent factors included CT variables such coronary vein diameter, portal vein (PV) diameter, lieno-renal shunt and other laboratory non-invasive variables namely FIB-4, APRI, and platelet count/splenic diameter. Receiver operating characteristic (ROC) curve was plotted to determine the accuracy of non-invasive parameters for predicting the presence of large esophageal varices and the area under the ROC curve for each one of these parameters was obtained. A model was established and the best model for prediction of large risky esophageal varices used both PC/SD and PV diameter (75% accuracy), while the logistic model equation was shown to be (PV diameter × -0.256) plus (PC/SD × -0.006) plus (8.155). Values nearing 2 or more denote

  4. Swimming exercise attenuates psychological dependence and voluntary methamphetamine consumption in methamphetamine withdrawn rats

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    Damghani, Fatemeh; Bigdeli, Imanollah; Miladi-Gorji, Hossein; Fadaei, Atefeh

    2016-01-01

    Objective(s): This study evaluated the effect of swimming exercise during spontaneous methamphetamine (METH) withdrawal on the anxiety, depression, obsessive-compulsive disorder (OCD) and voluntary METH consumption in METH-dependent rats. Materials and Methods: Male Wistar rats were repeatedly administered with bi-daily doses of METH (2 mg/kg, subcutaneous) over a period of 14 days. Exercised rats were submitted to swimming sessions (45 min/day, five days per week, for 14 days) during spontaneous METH-withdrawal. Then, all animals were tested for the assessment of anxiety by using the elevated plus-maze (EPM), the grooming behaviors (OCD), and depression using forced swimming test (FST) and voluntary METH consumption using a two-bottle choice (TBC) paradigm for the assessment of craving. Results: The results showed that the swimmer METH-withdrawn rats exhibited an increase in EPM open arm time and entries and a reduction of immobility and grooming behaviors compared with the sedentary METH groups. Also, voluntary METH consumption was less in the swimmer METH-withdrawn rats than the sedentary METH groups throughout 5–8 days. Conclusion: This study showed that regular swimming exercise reduced voluntary METH consumption in animal models of craving by reducing anxiety, OCD, and depression in the METH-withdrawn rats. Thus, physical training may be ameliorating some of the withdrawal behavioral consequences of METH. PMID:27482339

  5. Physiological levels of thrombospondin-1 decrease NO-dependent vasodilation in coronary microvessels from aged rats.

    Science.gov (United States)

    Nevitt, Chris; McKenzie, Grant; Christian, Katelyn; Austin, Jeff; Hencke, Sarah; Hoying, James; LeBlanc, Amanda

    2016-06-01

    Aging and cardiovascular disease are associated with the loss of nitric oxide (NO) signaling and a decline in the ability to increase coronary blood flow reserve (CFR). Thrombospondin-1 (Thbs-1), through binding of CD47, has been shown to limit NO-dependent vasodilation in peripheral vascular beds via formation of superoxide (O2 (-)). The present study tests the hypothesis that, similar to the peripheral vasculature, blocking CD47 will improve NO-mediated vasoreactivity in coronary arterioles from aged individuals, resulting in improved CFR. Isolated coronary arterioles from young (4 mo) or old (24 mo) female Fischer 344 rats were challenged with the NO donor, DEA-NONO-ate (1 × 10(-7) to 1 × 10(-4) M), and vessel relaxation and O2 (-) production was measured before and after Thbs-1, αCD47, and/or Tempol and catalase exposure. In vivo CFR was determined in anesthetized rats (1-3% isoflurane-balance O2) via injected microspheres following control IgG or αCD47 treatment (45 min). Isolated coronary arterioles from young and old rats relax similarly to exogenous NO, but addition of 2.2 nM Thbs-1 inhibited NO-mediated vasodilation by 24% in old rats, whereas young vessels were unaffected. Thbs-1 increased O2 (-) production in coronary arterioles from rats of both ages, but this was exaggerated in old rats. The addition of CD47 blocking antibody completely restored NO-dependent vasodilation in isolated arterioles from aged rats and attenuated O2 (-) production. Furthermore, αCD47 treatment increased CFR from 9.6 ± 9.3 (IgG) to 84.0 ± 23% in the left ventricle in intact, aged animals. These findings suggest that the influence of Thbs-1 and CD47 on coronary perfusion increases with aging and may be therapeutically targeted to reverse coronary microvascular dysfunction. PMID:27199114

  6. Pituitary glycoprotein hormone a-subunit secretion by cirrhotic patients

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    Oliveira M.C.

    1999-01-01

    Full Text Available Secretion of the a-subunit of pituitary glycoprotein hormones usually follows the secretion of intact gonadotropins and is increased in gonadal failure and decreased in isolated gonadotropin deficiency. The aim of the present study was to determine the levels of the a-subunit in the serum of patients with cirrhosis of the liver and to compare the results obtained for eugonadal cirrhotic patients with those obtained for cirrhotic patients with hypogonadotropic hypogonadism. Forty-seven of 63 patients with cirrhosis (74.6% presented hypogonadism (which was central in 45 cases and primary in 2, 7 were eugonadal, and 9 women were in normal menopause. The serum a-subunit was measured by the fluorimetric method using monoclonal antibodies. Cross-reactivity with LH, TSH, FSH and hCG was 6.5, 1.2, 4.3 and 1.1%, respectively, with an intra-assay coefficient of variation (CV of less than 5% and an interassay CV of 5%, and sensitivity limit of 4 ng/l. The serum a-subunit concentration ranged from 36 to 6253 ng/l, with a median of 273 ng/l. The median was 251 ng/l for patients with central hypogonadism and 198 ng/l for eugonadal patients. The correlation between the a-subunit and basal LH levels was significant both in the total sample (r = 0.48, P<0.01 and in the cirrhotic patients with central hypogonadism (r = 0.33, P = 0.02. Among men with central hypogonadism there was a negative correlation between a-subunit levels and total testosterone levels (r = 0.54, P<0.01 as well as free testosterone levels (r = -0.53, P<0.01. In conclusion, although the a-subunit levels are correlated with LH levels, at present they cannot be used as markers for hypogonadism in patients with cirrhosis of the liver.

  7. Antidepressant-like Effects of Buprenorphine in Rats Are Strain Dependent

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    Browne, Caroline A.; van Nest, Duncan; Lucki, Irwin

    2014-01-01

    The prevalence of major depressive disorder and the limited efficacy of conventional drug treatments provide significant impetus to develop novel and more rapidly acting antidepressants for individuals with treatment resistant forms of depression. The primary goal of these studies was to ascertain whether buprenorphine (BPN), a medically available drug with mixed effects at opioid receptors, was effective in behavioral tests using the Wistar Kyoto (WKY) rat strain, a rodent model of exaggerated depressive and anxiety behaviors that demonstrates resistance to certain antidepressants. As WKY rats are maintained by different sources, we assessed the behavioral effects of BPN using the modified rat forced swim test (FST) and the emergence test in WKY rat colonies obtained from different vendors. BPN dose-dependently reduced immobility and increased swimming behavior in the FST and reduced emergence latencies in two WKY lines (Charles River (WKY/NCrl) and Harlan laboratories (WKY/NHsd)) that also showed high baseline immobility in the FST. WKY rats from Taconic (WKY/NTac) did not show high baseline immobility in the FST or anxiety as had been previously reported, suggesting drift in the phenotype of rats from this supplier. Furthermore, BPN did not reduce immobility in the FST or reduce latencies in the emergence test in WKY rats from Taconic. BPN also failed to produce antidepressant-like effects in Wistar and Sprague-Dawley rats. These results indicate a striking strain-selectivity for the effects of BPN, producing antidepressant and anxiolytic-like responses in WKY/NCrl and WKY/NHsd lines but not in the normosensitive control Wistar and Sprague-Dawley strains. PMID:25453747

  8. Intrahepatic splenosis mimicking hepatocellular carcinoma in a cirrhotic liver

    International Nuclear Information System (INIS)

    We report a patient who has a cirrhotic liver secondary to hepatitis C virus infection with a liver lesion incidentally found on routine liver ultrasound. The patient had a history of splenectomy 30 years earlier. The magnetic resonance imaging (MRI) characteristics suggested the diagnosis of intrahepatic splenosis, which is confirmed by core needle biopsy. Knowledge of these imaging findings makes this entity important to be considered in the differential diagnosis of a hepatic tumor in the presence of a history of splenic trauma or surgery. (author)

  9. [A case of hepatic sarcoidosis presenting with cirrhotic symptoms].

    Science.gov (United States)

    Kaji, Kiichiro; Ogino, Hidero; Hirai, Satoshi; Shimatani, Akiyoshi; Horita, Yosuke; Matsuda, Kouichiro; Hiramatsu, Katsushi; Matsuda, Mitsuru; Shimizu, Koichi; Nakanishi, Yuko; Noda, Yatsugi

    2014-03-01

    A man in 40s with skin sarcoidosis presented with signs and symptoms of liver injury and thrombocytopenia. Enhanced computed tomography and magnetic resonance imaging revealed cholecystolithiasis, hepatic deformation, and giant splenomegaly. Gastrointestinal endoscopy showed esophageal varices. Cholecystectomy, splenectomy, and wedge biopsy of the liver were performed. Histopathology of the liver revealed many granulomas and severe periportal fibrosis without lobular reconstruction. These findings were compatible with hepatic sarcoidosis, but not liver cirrhosis. Here we report a rare case of hepatic sarcoidosis presenting with cirrhotic symptoms.

  10. Estrous Cycle-Dependent Phasic Changes in the Stoichiometry of Hippocampal Synaptic AMPA Receptors in Rats.

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    Hirobumi Tada

    Full Text Available Cognitive function can be affected by the estrous cycle. However, the effect of the estrous cycle on synaptic functions is poorly understood. Here we show that in female rats, inhibitory-avoidance (IA task (hippocampus-dependent contextual fear-learning task drives GluA2-lacking Ca2+-permeable AMPA receptors (CP-AMPARs into the hippocampal CA3-CA1 synapses during all periods of the estrous cycle except the proestrous period, when estrogen levels are high. In addition, IA task failed to drive CP-AMPARs into the CA3-CA1 synapses of ovariectomized rats only when estrogen was present. Thus, changes in the stoichiometry of AMPA receptors during learning depend on estrogen levels. Furthermore, the induction of long-term potentiation (LTP after IA task was prevented during the proestrous period, while intact LTP is still expressed after IA task during other period of the estrous cycle. Consistent with this finding, rats conditioned by IA training failed to acquire hippocampus-dependent Y-maze task during the proestrous period. On the other hand, during other estrous period, rats were able to learn Y-maze task after IA conditioning. These results suggest that high estrogen levels prevent the IA learning-induced delivery of CP-AMPARs into hippocampal CA3-CA1 synapses and limit synaptic plasticity after IA task, thus preventing the acquisition of additional learning.

  11. Estrous Cycle-Dependent Phasic Changes in the Stoichiometry of Hippocampal Synaptic AMPA Receptors in Rats.

    Science.gov (United States)

    Tada, Hirobumi; Koide, Mayu; Ara, Wakana; Shibata, Yusuke; Funabashi, Toshiya; Suyama, Kumiko; Goto, Takahisa; Takahashi, Takuya

    2015-01-01

    Cognitive function can be affected by the estrous cycle. However, the effect of the estrous cycle on synaptic functions is poorly understood. Here we show that in female rats, inhibitory-avoidance (IA) task (hippocampus-dependent contextual fear-learning task) drives GluA2-lacking Ca2+-permeable AMPA receptors (CP-AMPARs) into the hippocampal CA3-CA1 synapses during all periods of the estrous cycle except the proestrous period, when estrogen levels are high. In addition, IA task failed to drive CP-AMPARs into the CA3-CA1 synapses of ovariectomized rats only when estrogen was present. Thus, changes in the stoichiometry of AMPA receptors during learning depend on estrogen levels. Furthermore, the induction of long-term potentiation (LTP) after IA task was prevented during the proestrous period, while intact LTP is still expressed after IA task during other period of the estrous cycle. Consistent with this finding, rats conditioned by IA training failed to acquire hippocampus-dependent Y-maze task during the proestrous period. On the other hand, during other estrous period, rats were able to learn Y-maze task after IA conditioning. These results suggest that high estrogen levels prevent the IA learning-induced delivery of CP-AMPARs into hippocampal CA3-CA1 synapses and limit synaptic plasticity after IA task, thus preventing the acquisition of additional learning. PMID:26121335

  12. Distribution of nitric oxide synthase in normal and cirrhotic human liver

    Science.gov (United States)

    McNaughton, Lance; Puttagunta, Lakshmi; Martinez-Cuesta, Maria Angeles; Kneteman, Norm; Mayers, Irvin; Moqbel, Redwan; Hamid, Qutayba; Radomski, Marek W.

    2002-01-01

    Chronic liver disorders represent a serious health problem, considering that 300 million people worldwide are hepatitis B virus carriers, and 8,000–10,000 patients per year, in the U.S. alone, die as a result of liver failure caused by hepatitis C infection. Nitric oxide synthase (NOS) regulates hepatic vasculature; however, the patterns of expression and activity of NOS proteins in healthy and diseased human livers are unknown. Sections of diseased (n = 42) and control livers (n = 14) were collected during orthotopic liver transplants and partial hepatectomy. The diseased sections included alcoholic cirrhosis, viral hepatitis, cholestasis, acute necrosis, and uncommon pathologies including α1-anti-trypsin disorder. The endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS) were studied by using the citrulline assay, Western immunoblot, immunohistochemistry, and in situ hybridization. The systemic generation of plasma NO metabolites was measured by HPLC. In control livers, Ca2+-dependent and –independent NOS activities were identified by Western analysis as eNOS and iNOS, respectively. The eNOS was uniformly distributed in the hepatocytes and also detected in the endothelium of hepatic arteries, terminal hepatic venules, sinusoids, and in biliary epithelium. The iNOS was detected in hepatocytes and localized mainly in the periportal zone of the liver acinus. This pattern of distribution of eNOS and iNOS in normal liver was confirmed by in situ hybridization. In diseased livers, there was a significant increase in Ca2+-independent NOS with the corresponding strong appearance of iNOS in the cirrhotic areas. The eNOS was translocated to hepatocyte nuclei. Thus, eNOS and iNOS proteins are differentially expressed in healthy human liver, and this expression is significantly altered in cirrhotic liver disorders. PMID:12482944

  13. Cirrhotic cardiomyopathy: Implications for the perioperativemanagement of liver transplant patients

    Institute of Scientific and Technical Information of China (English)

    Suehana Rahman; Susan V Mallett

    2015-01-01

    Cirrhotic cardiomyopathy is a disease that has onlyrecently been recognised as a definitive clinical entity.In the setting of liver cirrhosis, it is characterizedby a blunted inotropic and chronotropic responseto stress, impaired diastolic relaxation of themyocardium and prolongation of the QT interval inthe absence of other known cardiac disease. A keypathological feature is the persistent over-activationof the sympathetic nervous system in cirrhosis, whichleads to down-regulation and dysfunction of theβ-adrenergic receptor. Diagnosis can be made using acombination of echocardiography (resting and stress),tissue Doppler imaging, cardiac magnetic resonanceimaging, 12-lead electrocardiogram and measurementof biomarkers. There are significant implications of cirrhoticcardiomyopathy in a number of clinical situations in whichthere is an increased physiological demand, whichcan lead to acute cardiac decompensation and heartfailure. Prior to transplantation there is an increasedrisk of hepatorenal syndrome, cardiac failure followingtransjugular intrahepatic portosystemic shunt insertionand increased risk of arrhythmias during acutegastrointestinal bleeding. Liver transplantation presentsthe greatest physiological challenge with a furtherrisk of acute cardiac decompensation. Peri-operativemanagement should involve appropriate choice of graftand minimization of large fluctuations in preload andafterload. The avoidance of cardiac failure during thisperiod has important prognostic implications, as thereis evidence to suggest a long-term resolution of theabnormalities in cirrhotic cardiomyopathy.

  14. MANAGEMENT OF PORTAL VEIN THROMBOSIS IN CIRRHOTIC PATIENTS

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    Maria Anna Guardascione

    2009-11-01

    Full Text Available

    Portal vein thrombosis (PVT not associated with hepatocellular carcinoma is considered a frequent complication of liver cirrhosis but, unlike PVT occurring in non-cirrhotic patients, very few data are available on its natural history and management.  The reduced portal blood flow velocity is the main determinant of PVT but, as in other venous thromboses, multiple factors local and systemic, inherited or acquired often can concur with. PVT has a variety of clinical presentations ranging from asymptomatic to life-threatening diseases like gastroesophageal bleeding or acute intestinal ischemia. It is usually diagnosed by Doppler ultrasound but computed tomography and magnetic resonance imaging are useful to study the extent of thrombosis and the involvement of the abdominal organs. The risk of bleeding mainly determined by the presence of gastroesophageal varices and clotting alterations causes concern for the treatment of PVT in cirrhotic patients. To date, anticoagulant therapy seems to be indicated only in patients awaiting liver transplantation. This review focuses on the definition of the subgroups of patients with cirrhosis that might benefit from treatment of PVT and examines the pros and cons of the available treatments in terms of efficacy, monitoring and safety, providing also perspectives for future studies.

  15. Synthesis of platelet-activating factor and its receptor expression in Kupffer cells in rat carbon tetrachloride-induced cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Yin-Ying Lu; Chun-Ping Wang; Lin Zhou; Yan Chen; Shu-Hui Su; Yong-Yi Feng; Yong-Ping Yang

    2008-01-01

    AIM:To determine the platelet-activating factor (PAF)synthesis and its receptor expression in Kupffer cells in rat carbon tetrachloride-induce dcirrhosis.METHODS:Kupffer cells,isolated from the livers of control and CCl4-induced cirrhotic rats,were placed in serum-free medium overnight.PAF saturation binding,ET-1 saturation and competition binding were assayed.ET-1 induced PAF synthesis,mRNA expression of PAF,preproendothelin-1,endothelin A (ETA) and endothelin B (ETB) receptors were also determined.RESULTS:A two-fold increase of PAF synthesis (1.42±0.14 vs 0.66±0.04 pg/μg DNA) and a 1.48-fold increase of membrane-bound PAF (1.02±0.06 vs 0.69±0.07 Pg/μg DNA) were observed in activated Kupffer cells of cirrhotic rats.The application of ET-1 to Kupffer cells induced PAF synthesis in a concentration-dependent manner in both cirrhotic and normal rats via ETB receptor,but PAF synthesis in the activated Kupffer cells was more effective than that in the normal Kupffer cells.In activated Kupffer cells,PAF receptor expression and PAF binding capacity were markedly enhanced.Activated Kupffer cells raised the [125I]-ET-1 binding capacity,but changed neither the affinity of the receptors,nor the expression of ETA receptor.CONCLUSION:Kupffer cells in the course of CCl4-induced cirrhosis are the main source of increased PAF.ET-1 is involved endogenously in stimulating the PAF synthesis in activated Kupffer cells via ETB receptor by paracrine.ETA receptor did not appear in activated Kupffer cells,which may exacerbate the hepatic and extrahepatic complications of cirrhosis.

  16. Chrysin, a flavonoid attenuates histological changes of hyperammonemic rats: A dose dependent study.

    Science.gov (United States)

    Renuka, Mani; Vijayakumar, Natesan; Ramakrishnan, Arumugam

    2016-08-01

    Chrysin (5,7-dihydroxyflavone) is a major component of some traditional medicinal herbs present in honey, propolis and many plant extracts. The study was aimed to illuminate the effect of chrysin in the pathogenesis of ammonium chloride (NH4Cl) induced hyperammonemic rat model in a dose dependent manner. Rats were injected with NH4Cl (100mg/kg b.w.) by intraperitonially (i.p) thrice a week for 8 consecutive weeks for the induction of experimental hyperammonemia. Hyperammonemic rats were treated with chrysin by orally at a dose of 25, 50 & 100mg/kg b.w. respectively. Protective effect of chrysin against hyperammonemia was evaluated by performing biochemical estimations and morphopathological investigations of hematoxylin and eosin stained sections of liver, brain and kidney tissues. Supplementation of chrysin reinstated the levels of blood ammonia, plasma urea, uric acid, total bilirubin, creatinine, brain glutamate, glutamine, nitric oxide (NO) and the activities of Na(+)/K(+)-ATPase, and liver marker enzymes. On the other hand increased level of plasma urea was observed in chrysin treated rats as compared with hyperammonemic rats. Chrysin administration caused distortion of hepatic, brain and kidney architecture as shown by histological examination. Chrysin at a dose (100mg/kg b.w.) showed an utmost decline in the level of all biochemical estimations. Both biochemical and morphological studies clearly revealed that chrysin protects against cell injury induced by ammonia intoxication in a dose-response manner with respect to endogenous antioxidants and hypoammonemic effects. PMID:27470372

  17. Supplier-dependent differences in intermittent voluntary alcohol intake and response to naltrexone in Wistar rats

    Directory of Open Access Journals (Sweden)

    Shima eMomeni

    2015-11-01

    Full Text Available Alcohol use disorder (AUD is a worldwide public health problem and a polygenetic disorder displaying substantial individual variation. This work aimed to study individual differences in behavior and its association to voluntary alcohol intake and subsequent response to naltrexone in a seamless heterogenic group of animals. Thus, by this approach the aim was to more accurately recapitulate the existing heterogeneity within the human population. Male Wistar rats from three different suppliers (Harlan Laboratories B.V., RccHanTM:WI; Taconic Farms A/S, HanTac:WH; and Charles River GmbH, Crl:WI were used to create a heterogenic group for studies of individual differences in behavior, associations to intermittent voluntary alcohol intake and subsequent response to naltrexone. The rats were tested in the open field prior to the Y-maze and then given voluntary intermittent access to alcohol or water in the home cage for six weeks, where after, naltrexone in three different doses or saline was administered in a Latin square design over four weeks and alcohol intake and preference was measured. However, supplier-dependent differences and concomitant skew subgroup formations, primarily in open field behavior and intermittent alcohol intake, resulted in a shifted focus to instead study voluntary alcohol intake and preference, and the ensuing response to naltrexone in Wistar rats from three different suppliers. The results showed that outbred Wistar rats are diverse with regard to voluntary alcohol intake and preference in a supplier-dependent manner; higher in RccHanTM:WI relative to HanTac:WH and Crl:WI. The results also revealed supplier-dependent differences in the effect of naltrexone that were dose- and time-dependent; evident differences in high-drinking RccHanTM:WI rats relative to HanTac:WH and Crl:WI rats. Overall these findings render RccHanTM:WI rats more suitable for studies of individual differences in voluntary alcohol intake and response to

  18. Convergent evidence from alcohol-dependent humans and rats for a hyperdopaminergic state in protracted abstinence.

    Science.gov (United States)

    Hirth, Natalie; Meinhardt, Marcus W; Noori, Hamid R; Salgado, Humberto; Torres-Ramirez, Oswaldo; Uhrig, Stefanie; Broccoli, Laura; Vengeliene, Valentina; Roßmanith, Martin; Perreau-Lenz, Stéphanie; Köhr, Georg; Sommer, Wolfgang H; Spanagel, Rainer; Hansson, Anita C

    2016-03-15

    A major hypothesis in addiction research is that alcohol induces neuroadaptations in the mesolimbic dopamine (DA) system and that these neuroadaptations represent a key neurochemical event in compulsive drug use and relapse. Whether these neuroadaptations lead to a hypo- or hyperdopaminergic state during abstinence is a long-standing, unresolved debate among addiction researchers. The answer is of critical importance for understanding the neurobiological mechanism of addictive behavior. Here we set out to study systematically the neuroadaptive changes in the DA system during the addiction cycle in alcohol-dependent patients and rats. In postmortem brain samples from human alcoholics we found a strong down-regulation of the D1 receptor- and DA transporter (DAT)-binding sites, but D2-like receptor binding was unaffected. To gain insight into the time course of these neuroadaptations, we compared the human data with that from alcohol-dependent rats at several time points during abstinence. We found a dynamic regulation of D1 and DAT during 3 wk of abstinence. After the third week the rat data mirrored our human data. This time point was characterized by elevated extracellular DA levels, lack of synaptic response to D1 stimulation, and augmented motor activity. Further functional evidence is given by a genetic rat model for hyperdopaminergia that resembles a phenocopy of alcohol-dependent rats during protracted abstinence. In summary, we provide a new dynamic model of abstinence-related changes in the striatal DA system; in this model a hyperdopaminergic state during protracted abstinence is associated with vulnerability for relapse. PMID:26903621

  19. Estrogen-dependent visceral hypersensitivity following stress in rats: An fMRI study.

    Science.gov (United States)

    Hubbard, Catherine S; Karpowicz, Jane M; Furman, Andrew J; da Silva, Joyce Teixeira; Seminowicz, David A; Traub, Richard J

    2016-01-01

    We used functional MRI and a longitudinal design to investigate the brain mechanisms in a previously reported estrogen-dependent visceral hypersensitivity model. We hypothesized that noxious visceral stimulation would be associated with activation of the insula, anterior cingulate cortex, and amygdala, and that estrogen-dependent, stress-induced visceral hypersensitivity would both enhance activation of these regions and recruit activation of other brain areas mediating affect and reward processing. Ovariectomized rats were treated with estrogen (17 β-estradiol, E2) or vehicle (n = 5 per group) and scanned in a 7T MRI at three different time points: pre-stress (baseline), 2 days post-stress, and 18 days post-stress. Stress was induced via a forced-swim paradigm. In a separate group of ovariectomized rats, E2 treatment induced visceral hypersensitivity at the 2 days post-stress time point, and this hypersensitivity returned to baseline at the 18 days post-stress time point. Vehicle-treated rats show no hypersensitivity following stress. During the MRI scans, rats were exposed to noxious colorectal distention. Across groups and time points, noxious visceral stimulation led to activations in the insula, anterior cingulate, and left amygdala, parabrachial nuclei, and cerebellum. A group-by-time interaction was seen in the right amygdala, ventral striatum-pallidum, cerebellum, hippocampus, mediodorsal thalamus, and pontine nuclei. Closer inspection of the data revealed that vehicle-treated rats showed consistent activations and deactivations across time, whereas estrogen-treated animals showed minimal deactivation with noxious visceral stimulation. This unexpected finding suggests that E2 may dramatically alter visceral nociceptive processing in the brain following an acute stressor. This study is the first to examine estrogen-stress dependent interactions in response to noxious visceral stimulation using functional MRI. Future studies that include other control groups

  20. Age-Dependent Increase of Absence Seizures and Intrinsic Frequency Dynamics of Sleep Spindles in Rats

    Directory of Open Access Journals (Sweden)

    Evgenia Sitnikova

    2014-01-01

    Full Text Available The risk of neurological diseases increases with age. In WAG/Rij rat model of absence epilepsy, the incidence of epileptic spike-wave discharges is known to be elevated with age. Considering close relationship between epileptic spike-wave discharges and physiologic sleep spindles, it was assumed that age-dependent increase of epileptic activity may affect time-frequency characteristics of sleep spindles. In order to examine this hypothesis, electroencephalograms (EEG were recorded in WAG/Rij rats successively at the ages 5, 7, and 9 months. Spike-wave discharges and sleep spindles were detected in frontal EEG channel. Sleep spindles were identified automatically using wavelet-based algorithm. Instantaneous (localized in time frequency of sleep spindles was determined using continuous wavelet transform of EEG signal, and intraspindle frequency dynamics were further examined. It was found that in 5-months-old rats epileptic activity has not fully developed (preclinical stage and sleep spindles demonstrated an increase of instantaneous frequency from beginning to the end. At the age of 7 and 9 months, when animals developed matured and longer epileptic discharges (symptomatic stage, their sleep spindles did not display changes of intrinsic frequency. The present data suggest that age-dependent increase of epileptic activity in WAG/Rij rats affects intrinsic dynamics of sleep spindle frequency.

  1. Age-dependent decrease in the hepatic uptake and biliary excretion of ouabain in rats.

    Science.gov (United States)

    Ohta, M; Kanai, S; Sato, Y; Kitani, K

    1988-03-01

    The biliary excretion of i.v. injected ouabain was examined in male and female Wistar-derived rats in relation to age. The hepatic uptake velocity for ouabain was also determined in isolated hepatocyte preparations obtained from male rats of various ages. Biliary recovery values of ouabain (percent of the dose) were fairly comparable for young male and female rats (3-4 month old). Recovery progressively decreased with age, the first 10-min recoveries at 24 months being about one-third those of respective young values in both sexes. A significant linear relation was demonstrated between the first 10-min recovery (Y, percent of the dose) and rat age (X, month), yielding the relations of Y = 17.75-0.43X for males and Y = 18.99-0.43X for females respectively. Similarly, the initial uptake velocity (Y, nmol/mg/min) for ouabain decreased in a linear fashion with age (X, month), yielding a significant negative correlation (Y = 0.704-0.0021X, r = -0.839, P less than 0.005, N = 21) at an ouabain concentration of 8 microM. Kinetic studies using non-linear regression analysis revealed a significantly lower Vmax value (0.533 +/- 0.041 nmol/mg/min) in old (24-29 months) rats compared to the young (4-4.5 months) value (1.193 +/- 0.105 nmol per mg/min, P less than 0.05), while the affinity constant (Km, microM) did not differ significantly between young and old animals (203.12 +/- 25.42 microM in young rats vs 283.68 +/- 28.90 microM in old rats, mean +/- SE, 0.05 less than P less than 0.1). The results of the present study suggest that the age-dependent decrease in the biliary recovery of i.v. injected ouabain in rats can be largely explained by the decrease with age in the hepatic uptake of ouabain. Furthermore, the results provide further support for our previous thesis that the decrease in the lateral mobility of hepatocyte plasma membrane proteins, as revealed by the fluorescence recovery after photobleaching technique, may play a significant role in the age-dependent

  2. Hormone-dependent aggression in male and female rats: experiential, hormonal, and neural foundations.

    Science.gov (United States)

    Albert, D J; Jonik, R H; Walsh, M L

    1992-01-01

    Hormone-dependent aggression in both male and female rats includes the distinctive behavioral characteristics of piloerection and lateral attack. In males the aggression is dependent on testicular testosterone and is commonly known as intermale aggression. In females, the aggression is most commonly observed as maternal aggression and is dependent on hormones whose identity is only beginning to emerge. The present review examines the experiential events which activate hormone-dependent aggression, the relation of the aggression to gonadal hormones, and the neural structures that participate in its modulation. In males and females, the aggression is activated by cohabitation with a conspecific of the opposite sex, by competitive experience, and by repeated exposure to unfamiliar conspecifics. In the female, the presence of pups also activates aggression. In both males and females, hormones are necessary for the full manifestation of the aggression. The essential hormone appears to be testosterone in males and a combination of testosterone and estradiol in females. The information available suggests the neural control systems for hormone-dependent aggression may be similar in males and females. It is argued that hormone-dependent aggression is behaviorally and biologically homologous in male and female rats.

  3. Vagal-dependent nonlinear variability in the respiratory pattern of anesthetized, spontaneously breathing rats

    OpenAIRE

    Dhingra, R. R.; Jacono, F. J.; Fishman, M; Loparo, K. A.; Rybak, I. A.; Dick, T E

    2011-01-01

    Physiological rhythms, including respiration, exhibit endogenous variability associated with health, and deviations from this are associated with disease. Specific changes in the linear and nonlinear sources of breathing variability have not been investigated. In this study, we used information theory-based techniques, combined with surrogate data testing, to quantify and characterize the vagal-dependent nonlinear pattern variability in urethane-anesthetized, spontaneously breathing adult rat...

  4. Duration-dependence of the effect of treadmill exercise on hyperactivity in attention deficit hyperactivity disorder rats

    OpenAIRE

    Ji, Eun-Sang; Kim, Chang-Ju; Park, Jun Heon; Bahn, Geon Ho

    2014-01-01

    Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioral disorder, and its symptoms are hyperactivity and deficits in learning and memory. Physical exercise increases dopamine synthesis and neuronal activity in various brain regions. In the present study, we investigate the duration-dependence of the treadmill exercise on hyperactivity in relation with dopamine expression in ADHD. Spontaneously hypertensive rats were used for the ADHD rats and Wistar-Kyoto rats were used fo...

  5. Cryptosporidium parvum Isolate-Dependent Postinfectious Jejunal Hypersensitivity and Mast Cell Accumulation in an Immunocompetent Rat Model▿

    OpenAIRE

    Khaldi, Samira; Gargala, Gilles; Le Goff, Laetitia; Parey, Simon; Francois, Arnaud; Fioramonti, Jean; Ballet, Jean-Jacques; Dupont, Jean-Paul; Ducrotté, Philippe; Favennec, Loïc

    2009-01-01

    Cryptosporidium spp. are a cause of self-limited diarrhea in immunocompetent hosts. In immunocompetent rats, Cryptosporidium parvum infection induced digestive hypersensitivity, a key pathophysiological factor in functional digestive disorders such as irritable bowel syndrome (IBS). In such a rat model, we sought to document whether jejunal hypersensitivity depends on C. parvum isolate and is associated with a mast cell accumulation. Five-day-old rats were orally administered 105 oocysts of e...

  6. Tissue distribution and vitamin D dependence of IMCAL in the rat

    International Nuclear Information System (INIS)

    Integral membrane calcium-binding protein (IMCAL) is a vitamin D-dependent integral membrane protein that binds calcium with relatively high affinity. Specific immunoassays for IMCAL utilizing rabbit polyclonal and mouse monoclonal antibodies were developed and applied to studies of its tissue distribution and regulation by vitamin D3 and dietary calcium in the rat. The results indicate that vitamin D-dependent, cross-reactive protein is present in small intestinal mucosa, cecal mucosa, bone, kidney, brain, testis, heart, lung, spleen, and skin. Rats maintained on a low- (0.02%) compared with a high- (2.0%) calcium diet had significantly higher content of IMCAL in duodenal mucosa, cecal mucosa, bone, kidney, brain, testis, and heart. Treatment of rats on the high-calcium diet with 1,25-dihydroxyvitamin D3 increased the IMCAL content of the duodenal mucosa, cecal mucosa, and kidney. The widespread tissue distribution of vitamin D-dependent IMCAL, its close correlation in intestinal mucosa with the calcium transport mechanism, and its occurrence in isolated preparations of enterocyte plasma membranes (microvillus and basolateral membranes) suggest that the protein is involved in the regulation of calcium flux in a number of cell types

  7. Individual differences in drug dependence in rats: the role of genetic factors and life events.

    Science.gov (United States)

    Ellenbroek, Bart A; van der Kam, Elizabeth L; van der Elst, Martine C J; Cools, Alexander R

    2005-12-01

    Drug dependence and addiction is a chronic mental illness that has far reaching consequences for society in terms of economic loss, health costs and judicial problems. A crucial question in drug addiction, is what factors are involved in its aetiology, and especially what mediates the shit from use to abuse. As in most other mental illnesses, addiction can best be described using the so-called three hit model, which states that a disease results from an interaction between genetic factors, early lie events and late environmental factors. However, the precise nature of these factors still remains to be elucidated. This present review discusses the results from an animal model in which these three different hit are currently being investigated. The apomorphine susceptible (APO-SUS) and apomorphine unsusceptible (APO-UNSUS) rats, originally selected on the basis of their behavioural response to the dopaminergic agonist apomorphine, were recently found to be genetically different in the number of gene copies of a component of the gamma-secretase complex called Aph-1b. Whereas APO-UNSUS rats have three copies of the gene, APO-SUS rats have either 1 or 2 copies. In addition we have shown that these rats show differences in cocaine and alcohol self-administration, and that both early life events and late environmental factors can alter this self-administration behaviour. Thus, the data so far support the hypothesis that the APO-SUS and APO-UNSUS rats offer an interesting animal model for drug dependence in which genes and environment interact. We finally propose a theoretical model which can explain this gene-environment interaction. PMID:16253227

  8. Age-dependent expression of forkhead box O proteins in the duodenum of rats

    Institute of Scientific and Technical Information of China (English)

    Pan HUANG; Zhen-qi ZHOU; Rui-hua HUANG; Bo ZHOU; Quan-wei WEI; Fang-xiong SHI

    2011-01-01

    The O subfamily of forkhead box (FoxO) proteins is the downstream effector of the insulin-like growth factor-1/phosphoinositide 3-kinase/protein kinase B (IGF-1/PI3K/PKB) signal pathway.The objective of the present study was to examine the expressions of three members of FoxO proteins,FoxO1,FoxO3a,and FoxO4 in the duodenum of Sprague-Dawley rats at different ages.The result demonstrated that the expression of FoxO4 in rat duodenum showed an age-dependent manner.At Day 21,there were no detectable localization and expression of FoxO4 in the duodenum,while,at Months 2 and 6,localization and expression of FoxO4 were distinct.In addition,FoxO4 staining was primarily concentrated in the cell nuclei of the lamina propria around the intestinal gland of the duodenum in 2-month-old rats,but was not detectable in the same area in 6-month-old rats.Our results showed also that although FoxO3a existed in the cytoplasm of the lamina propria at a low level at the 2- and 6-month marks,it was still not detectable at Day 21.Besides,FoxO1 was not detectable in all parts and stages.Taken together,our findings suggested that the cell-specific and age-dependent expressional patterns of FoxO4 and FoxO3a proteins in the duodenum play some roles in the development and growth performance of the rat duodenum.

  9. Insulin Radioimmunoassay for Clinical Research in Psychiatric, Pancreatic, Cirrhotic and Irradiated Patients

    International Nuclear Information System (INIS)

    A modified Hales-Randle method for insulin radioimmunoassay is described. An insulin response curve was established in normal cases after glucose loading. Pathological changes were then investigated in patients and animals before and after therapeutic, operative and radiological procedures. Four representative groups of this material will be illustrated. (1) Psychotic patients (acute and chronic schizophrenics, neurotics and depressives) were examined with the aim of learning about the variable effects produced by insulin shock-therapy, as well as for biochemical diagnosis purposes in psychotics. Highest insulin response curves were found in chronic schizophrenics with improvement after insulin therapy. Schizophrenics without improvement presented different curves. Lowest insulin values were found in acute schizophrenia. Depressives and anxiety neurotics showed insulin tolerance curves similar to those of non-psychotic patients. (2) Pancreatic patients. Special attention was paid to pancreatic carcinoma (insulinoma excepted). In most cases of pancreatic carcinoma a very low and flat insulin tolerance curve was found. The above findings may be of a diagnostic importance in this condition, which is clinically hardly recognized. (3) Liver cirrhotic patients. A special group of shunt operated patients was investigated. The study was performed on eight liver cirrhotics before and after porto-caval or reno-splenal shunt operation. The plasma insulin level was examined in the vena cava, renal and cubital blood. The influence of tolbutamide was analysed. The normally occurring retention of insulin by normal hepatic tissue was found to be considerably disturbed. Other interesting changes were observed. (4) The plasma insulin level in the radiologically exposed. Experimental and clinical studies were performed, with insulin doses before and after radiation. Whole body X-ray exposure (300 rads) to rats resulted in a rapid lowering of insulin or its disappearance. Recovery was

  10. Differences in viral kinetics between genotypes 1 and 3 of hepatitis C virus and between cirrhotic and non-cirrhotic patients during antiviral therapy

    Institute of Scientific and Technical Information of China (English)

    José Eymard Medeiros-Filho; Isabel Maria Vicente Guedes de Carvalho Mello; Jo(a)o Renato Rebello Pinho; Avidan U Neumann; Fernanda de Mello Malta; Luiz Caetano da Silva; Flair José Carrilho

    2006-01-01

    AIM: To evaluate the impact of hepatitis C virus (HCV)infection with genotype 1 or 3 and the presence or absence of liver cirrhosis (LC) in the early viral kinetics response to treatment.METHODS: Naive patients (n = 46) treated with interferon-α (IFN-α) and ribavirin and followed up with frequent early HCV-RNA determinations were analysed.Patients were infected with genotype 1 (n = 28, 7 with LC) or 3 (n = 18, 5 with LC).RESULTS: The first phase decline was larger in genotype 3 patients than in genotype 1 patients (1.72 vs 0.95log IU/mL, P < 0.001). The second phase slope decline was also larger in genotype 3 patients than in genotype 1 patients (0.87 vs 0.15 log/wk, P < 0.001). Differences were found in both cirrhotic and non-cirrhotic patients.Genotype 1 cirrhotic patients had a slower 2nd phase slope than non-cirrhotic patients (0.06 vs 0.18 log/wk, P< 0,02). None of genotype 1 cirrhotic patients had a 1stphase decline larger than 1 log (non-cirrhotic patients:55%, P < 0.02). A similar trend toward a slower 2ndphase slope was observed in genotype 3 cirrhotic patients but the 1st phase slope decline was not different.Sustained viral response was higher in genotype 3 patients than in genotype 1 patients ,(72% vs14%, P <0.001) and in genotype 1 non-cirrhotic patients than in genotype 1 cirrhotic patients (19% vs 0%). A second phase decline slower than 0.3 log per week was predictive of non-response in all groups.CONCLUSION: Genotype 3 has faster early viral decline than genotype 1. Cirrhosis correlates with a slower 2nd phase decline and possibly with a lower 1st phase slope decline in genotype 1 patients.

  11. ENDURANCE TRAINING AND GLUTATHIONE-DEPENDENT ANTIOXIDANT DEFENSE MECHANISM IN HEART OF THE DIABETIC RATS

    Directory of Open Access Journals (Sweden)

    Mustafa Atalay

    2003-06-01

    Full Text Available Regular physical exercise beneficially influences cardiac antioxidant defenses in normal rats. The aim of this study was to test whether endurance training can strengthen glutathione-dependent antioxidant defense mechanism and decrease lipid peroxidation in heart of the streptozotocin-induced diabetic rats. Redox status of glutathione in blood of diabetic rats in response to training and acute exercise was also examined. Eight weeks of treadmill training increased the endurance in streptozotocin-induced diabetic rats. It did not affect glutathione level in heart tissue at rest and also after exercise. On the other hand, endurance training decreased glutathione peroxidase activity in heart, while glutathione reductase and glutathione S-transferase activities were not affected either by acute exhaustive exercise or endurance training. Reduced and oxidized glutathione levels in blood were not affected by either training or acute exercise. Conjugated dienes levels in heart tissue were increased by acute exhaustive exercise and also 8 weeks treadmill training. Longer duration of exhaustion in trained group may have contributed to the increased conjugated dienes levels in heart after acute exercise. Our results suggest that endurance type exercise may make heart more susceptible to oxidative stress. Therefore it may be wise to combine aerobic exercise with insulin treatment to prevent its adverse effects on antioxidant defense in heart in patients with diabetes mellitus

  12. Carnosine content in skeletal muscle is dependent on vitamin B6 status in rats

    Directory of Open Access Journals (Sweden)

    Sofya eSuidasari

    2016-01-01

    Full Text Available Carnosine, a histidine-containing dipeptide, is well known to be associated with skeletal muscle performance. However, there is limited information on the effect of dietary micronutrients on muscle carnosine level. Pyridoxal 5′-phosphate (PLP, the active form of vitamin B6, is involved in amino acid metabolisms in the body as a co-factor. We hypothesized that enzymes involved in β-alanine biosynthesis, the rate-limiting precursor of carnosine, may also be PLP-dependent. Thus, we examined the effects of dietary vitamin B6 on the muscle carnosine content of rats. Male and female rats were fed a diet containing 1, 7, or 35 mg pyridoxine HCl/kg for 6 weeks. Carnosine in skeletal muscles was quantified by ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS. In the gastrocnemius muscle of male rats, carnosine concentration was significantly higher in the 7 and 35 mg groups (+70% and +61%, respectively than in the 1 mg pyridoxine HCl/kg group, whereas that in the soleus muscle of male rats was significantly higher only in the 7 mg group (+43% than in the 1 mg pyridoxine HCl/kg group (P<0.05. In both muscles of female rats, carnosine concentration was significantly higher in the 7 and 35 mg groups (+32% ~ +226% than in the 1 mg pyridoxine HCl/kg group (P<0.05. We also found that compared to the 1 mg group, β-alanine concentrations in the 7 and 35 mg groups were markedly elevated in gastrocnemius muscles of male (+153% and +148%, respectively, P<0.05 and female (+381% and +437%, respectively, P<0.05 rats. Noteworthy, the concentrations of ornithine in the 7 and 35 mg groups were decreased in gastrocnemius muscles of male rats (−46% and −54%, respectively, P<0.05, which strongly inversely correlated with β-alanine concentration (r=−0.84, P<0.01. In humans, 19% lower muscle carnosine content was found in soleus muscle of women of the lower plasma PLP tertile, but this was not observed in gastrocnemius muscle

  13. The role of glucocorticoids in sodium retention in cirrhotic patients

    DEFF Research Database (Denmark)

    Hansen, Martin Højmark; Kristensen, Steffen Skott; Schaffalitzky de Muckadell, Ove B;

    2012-01-01

    sodium retention evident in cirrhosis. The aim was to elucidate the role of glucocorticoids in sodium retention in decompensated cirrhotic patients. Methods. A randomized, double-blind, placebo-controlled, crossover study was performed in nine patients with alcoholic cirrhosis of the liver. A washout...... interval of 14 days separated the two periods. After a basal period of 36 h, dexamethasone (0.5 mg every 6 h) or placebo was given for two days. Urine was collected for 12 h periods, and the concentrations of sodium, potassium, creatinine, cortisol and cortisol metabolites were determined. Blood samples...... for hemoglobin, glucose, sodium, potassium, creatinine, aldosterone and cortisol were obtained daily. Results. Dexamethasone treatment decreased S-cortisol 92.3% (82.9-93.4%) (median and range) compared with that in the basal period. Natriuresis (dexamethasone - placebo) increased 55.1 (-26...

  14. Magnetic resonance imaging of the cirrhotic liver: Anupdate

    Institute of Scientific and Technical Information of China (English)

    Agnes Watanabe; Miguel Ramalho; Mamdoh AlObaidy; Hye Jin Kim; Fernanda G Velloni; Richard C Semelka

    2015-01-01

    Noninvasive imaging has become the standard forhepatocellular carcinoma (HCC) diagnosis in cirrhoticlivers. In this review paper, we go over the basics ofMR imaging in cirrhotic livers and describe the imagingappearance of a spectrum of hepatic nodules markingthe progression from regenerative nodules to low- andhigh-grade dysplastic nodules, and ultimately to HCCs.We detail and illustrate the typical imaging appearancesof different types of HCC including focal, multifocal,massive, diffuse/infiltrative, and intra-hepaticmetastases; with emphasis on the diagnostic value ofMR in imaging these lesions. We also shed some lighton liver imaging reporting and data system, and therole of different magnetic resonance imaging (MRI)contrast agents and future MRI techniques includingthe use of advanced MR pulse sequences and utilizationof hepatocyte-specific MRI contrast agents, and howthey might contribute to improving the diagnosticperformance of MRI in early stage HCC diagnosis.

  15. Apoptotic bone marrow CD34+ cells in cirrhotic patients

    Institute of Scientific and Technical Information of China (English)

    Shuang-Suo Dang; Wen-Jun Wang; Ning Gao; Shun-Da Wang; Mei Li; La-Yang Liu; Ming-Zhun Sun; Tao Dong

    2011-01-01

    AIM: To access the frequency and level of apoptotic CD34+ cells isolated from the marrow fluid of patients with post-hepatitis cirrhosis.METHODS: The frequency of bone marrow CD34+ cells and apoptotic bone marrow CD34+ cells in 31 in-patients with post-hepatitis cirrhosis (cirrhosis group), and 15 out-patients without liver or blood disorders (control group) was calculated by flow cytometry. Pa-rameters were collected to evaluate liver functions of patients in cirrhosis group.RESULTS: The percentage of normal bone marrow CD34+ cells was 6.30% ± 2.48% and 1.87% ± 0.53% (t = 3.906, P < 0.01) while that of apoptotic marrow CD34+ cells was 15.00% ± 15.81% and 5.73% ± 1.57% (t = 2.367, P < 0.05) in cirrhosis and control groups, re-spectively. The percentage of apoptotic marrow CD34+ cells was 6.25% ± 3.30% and 20.92 ± 18.5% (t = 2.409, P < 0.05) in Child-Pugh A and Child-Pugh B + C cirrhotic patients, respectively. The percentage of late apoptotic marrow CD34+ cells was positively correlated with the total bilirubin and aspartate aminotransferase serum levels in patients with cirrhosis.CONCLUSION: The status of CD34+ marrow cells in cirrhotic patients may suggest that the ability of he-matopoietic progenitor cells to transform into mature blood cells is impaired.

  16. Reinforcement magnitude modulation of rate dependent effects in pigeons and rats.

    Science.gov (United States)

    Ginsburg, Brett C; Pinkston, Jonathan W; Lamb, R J

    2011-08-01

    Response rate can influence the behavioral effects of many drugs. Reinforcement magnitude may also influence drug effects. Further, reinforcement magnitude can influence rate-dependent effects. For example, in an earlier report, we showed that rate-dependent effects of two antidepressants depended on reinforcement magnitude. The ability of reinforcement magnitude to interact with rate-dependency has not been well characterized. It is not known whether our previous results are specific to antidepressants or generalize to other drug classes. Here, we further examine rate-magnitude interactions by studying effects of two stimulants (d-amphetamine [0.32-5.6 mg/kg] and cocaine [0.32-10 mg/kg]) and two sedatives (chlordiazepoxide [1.78-32 mg/kg] and pentobarbital [1.0-17.8 mg/kg]) in pigeons responding under a 3-component multiple fixed-interval (FI) 300-s schedule maintained by 2-, 4-, or 8-s of food access. We also examine the effects of d-amphetamine [0.32-3.2 mg/kg] and pentobarbital [1.8-10 mg/kg] in rats responding under a similar multiple FI300-s schedule maintained by 2- or 10- food pellet (45 mg) delivery. In pigeons, cocaine and, to a lesser extent, chlordiazepoxide exerted rate-dependent effects that were diminished by increasing durations of food access. The relationship was less apparent for pentobarbital, and not present for d-amphetamine. In rats, rate-dependent effects of pentobarbital and d-amphetamine were not modulated by reinforcement magnitude. In conclusion, some drugs appear to exert rate-dependent effect which are diminished when reinforcement magnitude is relatively high. Subsequent analysis of the rate-dependency data suggest the effects of reinforcement magnitude may be due to a diminution of drug-induced increases in low-rate behavior that occurs early in the fixed-interval. PMID:21707192

  17. Association Between Proton Pump Inhibitor Use and Spontaneous Bacterial Peritonitis in Cirrhotic Patients with Ascites

    Directory of Open Access Journals (Sweden)

    Mélissa Ratelle

    2014-01-01

    Full Text Available BACKGROUND: There are data suggesting a link between proton pump inhibitor (PPI use and the development of spontaneous bacterial peritonitis (SBP in cirrhotic patients with ascites; however, these data are controversial.

  18. Age dependence of myosin heavy chain transitions induced by creatine depletion in rat skeletal muscle

    Science.gov (United States)

    Adams, Gregory R.; Baldwin, Kenneth M.

    1995-01-01

    This study was designed to test the hypothesis that myosin heavy chain (MHC) plasticity resulting from creatine depletion is an age-dependent process. At weaning (age 28 days), rat pups were placed on either standard rat chow (normal diet juvenile group) or the same chow supplemented with 1% wt/wt of the creatine analogue beta-guanidinopropionic acid (creatine depletion juvenile (CDJ) group). Two groups of adult rats (age approximately 8 wk) were placed on the same diet regimens (normal diet adult and creatine depletion adult (CDA) groups). After 40 days (CDJ and normal diet juvenile groups) and 60 days (CDA and normal diet adult groups), animals were killed and several skeletal muscles were removed for analysis of creatine content or MHC ditribution. In the CDJ group, creatine depletion (78%) was accompanied by significant shifts toward expression of slower MHC isoforms in two slow and three fast skeletal muscles. In contrast, creatine depletion in adult animals did not result in similar shifts toward slow MHC isoform expression in either muscle type. The results of this study indicate that there is a differential effect of creatine depletion on MHC tranitions that appears to be age dependent. These results strongly suggest that investigators contemplating experimental designs involving the use of the creatine analogue beta-guanidinopropionic acid should consider the age of the animals to be used.

  19. Spatial cognition following early-life seizures in rats: Performance deficits are dependent on task demands.

    Science.gov (United States)

    Barry, Jeremy M; Tian, Chengju; Spinella, Anthony; Page, Matias; Holmes, Gregory L

    2016-07-01

    Cognitive impairment is a common comorbidity in childhood epilepsy. Studies in rodents have demonstrated that frequent seizures during the first weeks of life result in impaired spatial cognition when the rats are tested as juvenile or adults. To determine if spatial cognitive deficits following early-life seizures are task-specific or similar across spatial tasks, we compared the effects of early-life seizures in two spatial assays: 1) the Morris water maze, a hippocampal-dependent task of spatial cognition and 2) the active avoidance task, a task that associates an aversive shock stimulus with a static spatial location that requires intact hippocampal-amygdala networks. Rats with early-life seizures tested as adults did not differ from control rats in the water maze. However, while animals with early-life seizures showed some evidence of learning the active avoidance task, they received significantly more shocks in later training trials, particularly during the second training day, than controls. One possibility for the performance differences between the tasks is that the active avoidance task requires multiple brain regions and that interregional communication could be affected by alterations in white matter integrity. However, there were no measurable group differences with regard to levels of myelination. The study suggests that elucidation of mild cognitive deficits seen following early-life seizures may be dependent on task features of active avoidance. PMID:27152463

  20. Caspase-dependent retinal ganglion cell apoptosis in the rat model of acute diabetes

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Background Neural apoptosis is generally believed to be mediated by two distinct pathways, caspase-dependant and caspase-independent pathways. This study investigated the apoptotic pathways involved in retinal ganglion ceils in acute diabetes in rats. Methods Diabetes was induced in male Wistar rats by a peritoneal injection of streptozotocin (STZ). Expression and localization of caspase-3 and apoptosis-inducing factor (AIF) proteins in the retina of diabetic rats was examined by Western blotting and immunohistochemistry analyses. Terminal transferase dUTP nick end labeling (TUNEL) assay and immunofluorescent staining specific for caspase-3 and AIF were applied to analyze for apoptosis of retinal ganglion cells. In addition, a caspase-3 inhibitor DEVD-CHO was injected intravitreally to further determine the apoptotic pathways of retinal ganglion cells triggered in acute diabetes. Results Two weeks after induction of diabetes, a significant increase in caspase-3 protein expression and localization occurred in the nerve fiber layer, ganglion cell layer, and inner plexiform layer of the retina. Four weeks after the onset of diabetes, the increase in caspase-3 expression was profound eight weeks postinduction of diabetes (P<0.05). Meanwhile, no AIF protein expression was detected in this study. In addition, intravitreal administration of the caspase-3 inhibitor DEVD-CHO reduced apoptosis of retinal ganglion cells by its direct inhibitory action on caspase-3. Conclusion Caspase-dependent apoptotic pathways may be the main stimulant of STZ-induced retinal ganglion cell apoptosis in acute diabetes.

  1. Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats

    OpenAIRE

    Spiga, S.; Talani, G; Mulas, G.; Licheri, V; Fois, GR; Muggironi, G; Masala, N; Cannizzaro, C; Biggio, G; E. Sanna; Diana, M.

    2014-01-01

    This paper examines the intimate neuroarchitecture of the nucleus accumbens shell region and how it affects synaptic plasticity in alcohol-dependent rats. To do so, a simultaneous morphometrical/immunofluorescence method was applied to visualize various types of dendritic spines and patch-clamp techniques to detect changes in synaptic currents. Using these tools, we show a selective loss of “long thin” spines accompanied by an impaired long-term depression (LTD) in alcohol-dependent rats. Dop...

  2. (-)Epicatechin induces and modulates endothelium-dependent relaxation in isolated rat mesenteric artery rings

    Institute of Scientific and Technical Information of China (English)

    YAO Xiao-Qiang; CHAN Franky Leung; LAU Chi-Wai; HUANG Yu

    2002-01-01

    AIM: The present study was aimed to examine the role of endothelial nitric oxide in the relaxant response to green tea (-)epicatechin and its modulation of endothelium-mediated relaxation in the isolated rat mesenteric artery rings.METHODS: Changes in the isometric tension were measured with Grass force-displacement transducers. RESULTS:The (-)epicatechin-induced relaxation was largely dependent on the presence of intact endothelium and was reversed by NG-nitro-L-arginine methyl ester 10 μmol/L or methylene blue 10 μmol/L, the inhibitors of nitric oxidemediated relaxation. L-Arginine at 1 mmol/L antagonized the effect of L-NAME or methylene blue. Pretreatment of endothelium-intact rings with (-)epicatechin 10 μmol/L enhanced the relaxation induced by endothelium-dependent vasodilator, acetylcholine, while this concentration did not influence the endothelium-independent relaxation induced by sodium nitroprusside in the endothelium-denuded artery rings. CONCLUSION: The results indicate that the endothelium-dependent vasodilation by (-)epicatechin is mainly mediated through nitric oxide and low concentration of (-)epicatechin augments endothelium-dependent vasorelaxation in the rat mesenteric arteries.

  3. Carnosine Content in Skeletal Muscle Is Dependent on Vitamin B6 Status in Rats.

    Science.gov (United States)

    Suidasari, Sofya; Stautemas, Jan; Uragami, Shinji; Yanaka, Noriyuki; Derave, Wim; Kato, Norihisa

    2015-01-01

    Carnosine, a histidine-containing dipeptide, is well known to be associated with skeletal muscle performance. However, there is limited information on the effect of dietary micronutrients on muscle carnosine level. Pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, is involved in amino acid metabolisms in the body as a cofactor. We hypothesized that enzymes involved in β-alanine biosynthesis, the rate-limiting precursor of carnosine, may also be PLP dependent. Thus, we examined the effects of dietary vitamin B6 on the muscle carnosine content of rats. Male and female rats were fed a diet containing 1, 7, or 35 mg pyridoxine (PN) HCl/kg for 6 weeks. Carnosine in skeletal muscles was quantified by ultra-performance liquid chromatography coupled with tandem mass spectrometry. In the gastrocnemius muscle of male rats, carnosine concentration was significantly higher in the 7 and 35 mg groups (+70 and +61%, respectively) than in the 1 mg PN HCl/kg group, whereas that in the soleus muscle of male rats was significantly higher only in the 7 mg group (+43%) than in the 1 mg PN HCl/kg group (P carnosine concentration was significantly higher in the 7 and 35 mg groups (+32 to +226%) than in the 1 mg PN HCl/kg group (P carnosine content was found in soleus muscle of women of the lower plasma PLP tertile, but this was not observed in gastrocnemius muscle or in men. We conclude that adequate dietary vitamin B6 is essential for maintaining carnosine in skeletal muscles of rats. Significantly lower soleus carnosine content among women close to PLP deficiency suggests that a similar phenomenon exists in the humans. PMID:26835452

  4. Efficient activation of reconstructed rat embryos by cyclin-dependent kinase inhibitors.

    Directory of Open Access Journals (Sweden)

    Robin L Webb

    Full Text Available BACKGROUND: Over the last decade a number of species, from farm animals to rodents, have been cloned using somatic cell nuclear transfer technology (SCNT. This technique has the potential to revolutionize the way that genetically modified animals are made. In its current state, the process of SCNT is very inefficient (<5% success rate, with several technical and biological hurdles hindering development. Yet, SCNT provides investigators with powerful advantages over other approaches, such as allowing for prescreening for the desired level of transgene expression and eliminating the excess production of undesirable wild-type animals. The rat plays a significant role in biomedical research, but SCNT has been problematic for this species. In this study, we address one aspect of the problem by evaluating methods of activation in artificially constructed rat embryos. PRINCIPAL FINDINGS: We demonstrate that treatment with a calcium ionophore (ionomycin combined with a variety of cyclin-dependent kinase inhibitors is an effective way to activate rat embryos. This is in contrast to methods developed for the mouse embryo, which tolerates much less specific chemical treatments. Methods developed to activate mouse embryos do not translate well to rat embryos. CONCLUSIONS: Activation methods developed for one species will not necessarily translate to another species, even if it is closely related. Further, the parthenogenic response to chemical activators is not always a reliable indicator of how reconstructed embryos will react to the same activation method. A better understanding of rat oocyte physiology, although essential for developing better models of disease, may also provide insights that will be useful for making the SCNT process more efficient.

  5. No effect of oral testosterone treatment on sexual dysfunction in alcoholic cirrhotic men

    DEFF Research Database (Denmark)

    Gluud, C; Wantzin, P; Eriksen, J

    1988-01-01

    The prevalence and course of sexual dysfunction was evaluated in 221 alcoholic cirrhotic men participating in a double-blind, placebo-controlled study on the effect of oral testosterone treatment on liver disease. At entry, 67% (95% confidence limits, 61%-74%) complained of sexual dysfunction....... In conclusion, oral testosterone treatment does not significantly influence the type or course of sexual dysfunction in alcoholic cirrhotic men. However, sexual function improved after reduction of ethanol consumption in these patients....

  6. The effects of Helicobacter pylori infection on hyperammonaemia and hepatic encephalopathy in cirrhotic patients

    Institute of Scientific and Technical Information of China (English)

    王良静

    2006-01-01

    Objective To evaluate the relationship among Helicobacter pylori (Hp) infection, blood ammonia concentrations , and hepatic encephalopathy (HE) status, and to investigate the effect of Hp eradication on blood ammonia levels and hepatic encephalopathy status in cirrhotic patients. Methods From July 2003 to Jan 2005, cirrhotic patients in 5 regions of Zhejiang Province were enrolled. Patients were evaluated for the demographic checklists, number connection test, Hp infection, liver impairment level, blood ammonia concentrations and he-

  7. Dose-dependent ultrastructural changes in rat cornea after oral methylphenidate administration

    International Nuclear Information System (INIS)

    Objective was to investigate dose-dependent ultrastructural changes in rat cornea after oral methylphenidate (Ritalin) administration. This study was conducted in the Dept. of Anatomy, Gazi University, Faculty of Medicine, Ankara between March and May 2005, with a total of 27 female prepubertal Wistar albino rats, divided into 3 different dose groups (5mg/kg, 10 mg/kg, 20 mg/kg) and their control groups. They were treated orally with methylphenidate and eye tissue was removed to process for electron microscopic studies. We observed that all cells and prominently basal cells of the corneal epithelium show dose-dependent degenerative changes such as apoptotic bodies, chromatin condensation and ondulation in their nuclei and crystolysis of the mitochondrion. In the stroma, the most evident finding was the increase of the collagen fiber. In addition to dose-dependent changes related to apoptotic process, which is chromatin condensation in their nuclei, electron dense material accumulation and percicellular edema in the cytoplasm were also seen. In the endothelial cell lines, disruption of the junctional complexes, vacuolization in the cell cytoplasms and crystolysis of the mitochondrion's with rough endoplasmic reticulum cisternae activity were observed. Ritalin is inducing an evident degeneration, especially in epithelium cells with increasing doses. Ultrastructural cell organelle composition degeneration with stromal fibrosis has negative effect on cornea dehydration. In light of these findings, we believe that the Ritalin treatment dose needed to be kept to a minimum to maintain healthy cornea ultrastructure and related physiology. (author)

  8. Functional expression of double-stranded RNA-dependent protein kinase in rat intestinal epithelial cells.

    Science.gov (United States)

    Sato, Nagahiro; Morimoto, Hiroyuki; Baba, Ryoko; Nakamata, Junichi; Doi, Yoshiaki; Yamaguchi, Koji

    2010-05-01

    Intestinal epithelial cells (IECs) are exposed to external environment, microbial and viral products, and serve as essential barriers to antigens. Recent studies have shown that IECs express Toll-like receptors (TLRs) and respond to microbial components. The antimicrobial and antiviral barriers consist of many molecules including TLRs. To investigate the further component of this barrier in intestine, we examined the expression of double-stranded RNA-dependent protein kinase (PKR). PKR is a player in the cellular antiviral response and phosphorylates alpha-subunit of the eukaryotic translation initiation factor 2 (eIF-2alpha) to block protein synthesis and induces apoptosis. In this study, we showed that the expression of PKR was restricted to the cytoplasm of absorptive epithelial cells in the intestine of adult rat. We also demonstrated that PKR was expressed in the cultured rat intestinal epithelial cells (IEC-6). The level of PKR protein expression and the activity of alkaline phosphatase (ALP) increased in the cultured IEC-6 cells in a time-dependent manner. Inhibition of PKR by the 2-aminopurine treatment decreased ALP activity in the IEC-6 cells. Treatment of IEC-6 cells with synthetic double-stranded RNA (dsRNA) induced cell death in a dose-dependent manner. The addition of hydrocortisone also provoked suppression of PKR expression and ALP activity. This modulation might be mediated by signal transducers and activators of transcription-1 (STAT-1) protein. We concluded that PKR is expressed in IECs as potent barriers to antigens and is a possible modulator of the differentiation of rat IECs. PMID:20213745

  9. Clinical Significance of a Myeloperoxidase Gene Polymorphism and Inducible Nitric Oxide Synthase Expression in Cirrhotic Patients with Hepatopulmonary Syndrome

    Institute of Scientific and Technical Information of China (English)

    王燕颖; 王文多; 张艳霞; 赵欣; 杨东亮

    2010-01-01

    The clinical significance of a myeloperoxidase (MPO) gene polymorphism and inducible nitric oxide synthase (iNOS) expression in cirrhotic patients with hepatopulmonary syndrome (HPS) was explored. Enrolled subjects were divided into three groups according to their disease/health conditions: the HPS group (cirrhotic patients with HPS; n=63), the non-HPS group (cirrhotic patients without HPS; n=182), and the control group (healthy subjects without liver disease; n=35). The distribution of the MPO-463 G/A geno...

  10. Experimentally induced postinhibitory rebound in rat nucleus ambiguus is dependent on hyperpolarization parameters and membrane potential.

    Science.gov (United States)

    Dean, J B; Czyzyk-Krzeska, M; Millhorn, D E

    1989-06-01

    Postinhibitory rebound (PIR), a transient depolarization subsequent to release from experimental hyperpolarization, was identified and characterized in 81% of the cells studied in the nucleus ambiguus in slices from medulla of rat. Hyperpolarizing current pulses were administered via the recording microelectrode in the bridge-balanced mode to test for PIR. The voltage trajectory was characterized by a depolarizing sag during the pulse, rebound depolarization (PIR) after the pulse and increased input resistance during rebound. The amplitude and time course of PIR were dependent on prepulse membrane potential, pulse amplitude and pulse duration. These results suggest a potential role of PIR in respiratory rhythmogenesis. PMID:2771207

  11. Estrous Cycle-Dependent Phasic Changes in the Stoichiometry of Hippocampal Synaptic AMPA Receptors in Rats

    OpenAIRE

    Hirobumi Tada; Mayu Koide; Wakana Ara; Yusuke Shibata; Toshiya Funabashi; Kumiko Suyama; Takahisa Goto; Takuya Takahashi

    2015-01-01

    Cognitive function can be affected by the estrous cycle. However, the effect of the estrous cycle on synaptic functions is poorly understood. Here we show that in female rats, inhibitory-avoidance (IA) task (hippocampus-dependent contextual fear-learning task) drives GluA2-lacking Ca2+-permeable AMPA receptors (CP-AMPARs) into the hippocampal CA3-CA1 synapses during all periods of the estrous cycle except the proestrous period, when estrogen levels are high. In addition, IA task failed to dri...

  12. Strain-dependent variations in spatial learning and in hippocampal synaptic plasticity in the dentate gyrus of freely behaving rats

    Directory of Open Access Journals (Sweden)

    Denise eManahan-Vaughan

    2011-03-01

    Full Text Available Hippocampal synaptic plasticity is believed to comprise the cellular basis for spatial learning. Strain-dependent differences in synaptic plasticity in the CA1 region have been reported. However, it is not known whether these differences extend to other synapses within the trisynaptic circuit, although there is evidence for morphological variations within that path. We investigated whether Wistar and Hooded Lister (HL rat strains express differences in synaptic plasticity in the dentate gyrus in vivo. We also explored whether they exhibit differences in the ability to engage in spatial learning in an 8-arm radial maze. Basal synaptic transmission was stable over a 24h period in both rat strains, and the input-output relationship of both strains was not significantly different. Paired-pulse analysis revealed significantly less paired-pulse facilitation in the Hooded Lister strain when pulses were given 40-100 msec apart. Low frequency stimulation at 1Hz evoked long-term depression (>24h in Wistar and short-term depression (<2h in HL rats; 200Hz stimulation induced long-term potentiation (>24h in Wistar, and a transient, significantly smaller potentiation (<1h in HL rats, suggesting that HL rats have higher thresholds for expression of persistent synaptic plasticity. Training for 10d in an 8-arm radial maze revealed that HL rats master the working memory task faster than Wistar rats, although both strains show an equivalent performance by the end of the trial period. HL rats also perform more efficiently in a double working and reference memory task. On the other hand, Wistar rats show better reference memory performance on the final (8-10 days of training. Wistar rats were less active and more anxious than HL rats.These data suggest that strain-dependent variations in hippocampal synaptic plasticity occur in different hippocampal synapses. A clear correlation with differences in spatial learning is not evident however.

  13. Medial accumbens lesions attenuate testosterone-dependent aggression in male rats.

    Science.gov (United States)

    Albert, D J; Petrovic, D M; Walsh, M L; Jonik, R H

    1989-10-01

    Male hooded rats were castrated and implanted with testosterone-filled Silastic tubes appropriate for maintaining a normal average serum testosterone concentration. They were then given lesions of the medial accumbens nucleus or sham lesions. Twenty-four hours postoperatively each male was housed with a female. Beginning 7 days following pairing and continuing once each week for 4 weeks, each lesioned or sham-lesioned male was observed for aggression toward an unfamiliar male intruder. On the day following each test of aggression toward an unfamiliar male, each lesioned and sham-lesioned male was assessed for defensiveness toward an experimenter. Rats with medial accumbens lesions displayed significantly less aggression toward an unfamiliar male intruder during each of the weekly tests than did sham-lesioned animals. The attenuation was most pronounced in animals with lesions damaging the posterior part of the medial accumbens nucleus (also designated as anterior portion of the bed nucleus of the stria terminalis) in the region of the crossover of the anterior commissure. Although medial accumbens lesions are known to make individually housed rats hyperdefensive toward an experimenter, lesion-induced hyperdefensiveness was not observed in the pair-housed animals in the present experiment. It is argued that the medial accumbens/bed nucleus of the stria terminalis area is an important region in the anterior forebrain for the modulation of hormone-dependent aggression.

  14. Sex-dependent maternal deprivation effects on brain monoamine content in adolescent rats.

    Science.gov (United States)

    Llorente, Ricardo; O'Shea, Esther; Gutierrez-Lopez, M Dolores; Llorente-Berzal, Alvaro; Colado, María Isabel; Viveros, María-Paz

    2010-07-26

    Rats subjected to a single prolonged episode of maternal deprivation (MD) [24h, postnatal days 9-10] show, later in life, behavioural alterations that resemble specific signs of schizophrenia and other neuropsychiatric signs including increased levels of impulsivity and an apparent difficulty to cope with stressful situations. Some of these behavioural modifications are observable in the periadolescent period. However there is no previous information regarding the possible underlying neurochemical correlates at this critical developmental period. In this study we have addressed the effects of MD on the levels of serotonin (5-HT), dopamine (DA) and their respective metabolites in prefrontal cortex, hippocampus, striatum, midbrain and cerebellum of male and female periadolescent Wistar rats. MD rats showed significantly increased levels of 5-HT in all regions studied with the exception of cerebellum. In addition, MD animals showed increased levels of DA in PFC as well as increased levels of DA and a decrease of DOPAC/DA and HVA/DA ratios in striatum. The effect of MD on the monoaminergic systems was in several cases sex-dependent.

  15. State-dependent amygdala stimulation-induced cardiovascular effects in rats.

    Science.gov (United States)

    Chiou, Ruei-Jen; Kuo, Chung-Chih; Liang, Keng-Chen; Yen, Chen-Tung

    2009-12-31

    Stimulation of the amygdala is known to produce pressor, depressor, or has no effects. The present study was performed to test whether amygdala cardiovascular effects are influenced by consciousness states and by different types of anesthetics. Adult rats were set up for stimulation amygdala and measurement of blood pressure in a chronic preparation. After recovery, same sites of the amygdala were stimulated electrically for several trials with the rat under conscious or anesthetic states induced by pentobarbital, urethane, ketamine, alpha-chloralose and urethane plus alpha-chloralose, respectively. The interval between any two stimulation trials was at least 2 days. The stimulation was an 80-Hz, 0.5-ms, 100-micro A square wave pulse train lasting for 15 s. Cardiovascular responsive sites were found in the central, medial, and basolateral nuclei of the amygdala. In stimulating these responsive sites, significantly different cardiovascular effects were induced under a conscious state and an anesthetized state of the animal, yet no significant differences were found among the various anesthetic agents. We conclude, that the cardiovascular influence of the amygdala is state-dependent in the rat.

  16. Chlorogenic acid differentially affects postprandial glucose and glucose-dependent insulinotropic polypeptide response in rats.

    Science.gov (United States)

    Tunnicliffe, Jasmine M; Eller, Lindsay K; Reimer, Raylene A; Hittel, Dustin S; Shearer, Jane

    2011-10-01

    Regular coffee consumption significantly lowers the risk of type 2 diabetes (T2D). Coffee contains thousands of compounds; however, the specific component(s) responsible for this reduced risk is unknown. Chlorogenic acids (CGA) found in brewed coffee inhibit intestinal glucose uptake in vitro. The objective of this study was to elucidate the mechanisms by which CGA acts to mediate blood glucose response in vivo. Conscious, unrestrained, male Sprague-Dawley rats were chronically catheterized and gavage-fed a standardized meal (59% carbohydrate, 25% fat, 12% protein), administered with or without CGA (120 mg·kg(-1)), in a randomized crossover design separated by a 3-day washout period. Acetaminophen was co-administered to assess the effects of CGA on gastric emptying. The incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were measured. GLP-1 response in the presence of glucose and CGA was further examined, using the human colon cell line NCI-H716. Total area under the curve (AUC) for blood glucose was significantly attenuated in rats fed CGA (p gastric emptying was not altered. Plasma GIP response was blunted in rats fed CGA, with a lower peak concentration and AUC up to 180 min postprandially (p alterations seen in GIP concentrations. Given the widespread consumption and availability of coffee, CGA may be a viable prevention tool for T2D. PMID:21977912

  17. The role of basolateral amygdala adrenergic receptors in hippocampus dependent spatial memory in rat

    Directory of Open Access Journals (Sweden)

    Vafaei A.L.

    2008-03-01

    Full Text Available Background and the purpose of the study: There are extensive evidences indicating that the noradrenergic system of the basolateral nucleus of the amygdala (BLA is involved in memory processes. The present study investigated the role of the BLA adrenergic receptors (ARs in hippocampus dependent spatial memory in place avoidance task in male rat. Material and Methods: Long Evans rats (n=150 were trained to avoid footshock in a 60° segment while foraging for scattered food on a circular (80-cm diameter arena. The rats were injected bilaterally in the BLA specific ARS (Adrenergic receptors agonist norepinephrine (NE, 0.5 and 1 µg/µl and specific β-ARs antagonist propranolol (PRO, 0.5 and 1 µg/µl before acquisition, after training or before retrieval of the place avoidance task. Control rats received vehicle at the same volume. The learning in a single 30-min session was assessed 24h later by a 30-min extinction trial in which the time to first entrance and the number of entrances to the shocked area measured the avoidance memory. Results: Acquisition and consolidation were enhanced and impaired significantly by NE and PRO when the drugs were injected 10 min before or immediately after training, respectively. In contrast, neither NE nor PRO influenced animal performances when injected before retention testing. Conclusion: Findings of this study indicates that adrenergic system of the BLA plays an important role in regulation of memory storage and show further evidences for the opinion that the BLA plays an important role in integrating hormonal and neurotransmitter influences on memory storage.

  18. Preliminary study on androgen dependence of calcitonin gene-related peptide in rat penis

    Institute of Scientific and Technical Information of China (English)

    Zhou-Jun Shen; Shan-Wen Chen; Ying-Li Lu; Liao-Yuan Li; Xie-Lai Zhou; Ming-Guang Zhang; Zhao-Dian Chen

    2005-01-01

    Aim: To study the androgen dependence of the neurotransmitter, calcitonin gene-related peptide (CGRP) in rat penis.Methods: Forty-four Sprague-Dawley rats were randomly divided into Group A (intact controls), Group B (castrated)group were anaesthetized. Blood samples were taken for the measurement of serum testosterone and dihydrotestosterone (DHT) by means of radioimmunoassay. Penile samples were harvested for the investigation of calcitonin gene related peptide (CGRP)-immunoreactive nerve fibers with immunohistochemistry. The computer-assisted imaging analysis system was applied to calculate the area proportion of the CGRP-positive nerve fibers (CGRP-PNF) in each group.Results: 1) Both 4 and 10 weeks later, testosterone and DHT levels in Group B decreased significantly compared with those in Group A, (P<0.05, P<0.01, respectively); DHT level in Group C was also significantly decreased in comparison with that in Group A for both 4- and 10- week animals (P < 0.05); 2) There was no significant differences in area proportion of CGRP-PNF among Groups A, B and C 4 weeks after treatments (P > 0.05); However, 10weeks later, the proportion of CGRP-PNF in Groups B and C was significantly less than that in Group A (P < 0.01);3) The proportion of CGRP-PNF of 4-week animals in Groups B and C was significantly higher than that of 10-week animals (P<0.05). Conclusion: The expression of neurotransmitter, CGRP may depend on androgens, including testosterone and DHT in rat penis.

  19. Alcohol binge drinking during adolescence or dependence during adulthood reduces prefrontal myelin in male rats.

    Science.gov (United States)

    Vargas, Wanette M; Bengston, Lynn; Gilpin, Nicholas W; Whitcomb, Brian W; Richardson, Heather N

    2014-10-29

    Teen binge drinking is associated with low frontal white matter integrity and increased risk of alcoholism in adulthood. This neuropathology may result from alcohol exposure or reflect a pre-existing condition in people prone to addiction. Here we used rodent models with documented clinical relevance to adolescent binge drinking and alcoholism in humans to test whether alcohol damages myelinated axons of the prefrontal cortex. In Experiment 1, outbred male Wistar rats self-administered sweetened alcohol or sweetened water intermittently for 2 weeks during early adolescence. In adulthood, drinking behavior was tested under nondependent conditions or after dependence induced by 1 month of alcohol vapor intoxication/withdrawal cycles, and prefrontal myelin was examined 1 month into abstinence. Adolescent binge drinking or adult dependence induction reduced the size of the anterior branches of the corpus callosum, i.e., forceps minor (CCFM), and this neuropathology correlated with higher relapse-like drinking in adulthood. Degraded myelin basic protein in the gray matter medial to the CCFM of binge rats indicated myelin was damaged on axons in the mPFC. In follow-up studies we found that binge drinking reduced myelin density in the mPFC in adolescent rats (Experiment 2) and heavier drinking predicted worse performance on the T-maze working memory task in adulthood (Experiment 3). These findings establish a causal role of voluntary alcohol on myelin and give insight into specific prefrontal axons that are both sensitive to alcohol and could contribute to the behavioral and cognitive impairments associated with early onset drinking and alcoholism.

  20. Motor vehicle accidents: How should cirrhotic patients be managed?

    Institute of Scientific and Technical Information of China (English)

    Takumi Kawaguchi; Eitaro Taniguchi; Michio Sata

    2012-01-01

    Motor vehicle accidents (MVAs) are serious social issues worldwide and driver illness is an important cause of MVAs.Minimal hepatic encephalopathy (MHE) is a complex cognitive dysfunction with attention deficit,which frequently occurs in cirrhotic patients independent of severity of liver disease.Although MHE is known as a risk factor for MVAs,the impact of diagnosis and treatment of MHE on MVA-related societal costs is largely unknown.Recently,Bajaj et al demonstrated valuable findings that the diagnosis of MHE by rapid screening using the inhibitory control test (ICT),and subsequent treatment with lactulose could substantially reduce the societal costs by preventing MVAs,Besides the ICT and lactulose,there are various diagnostic tools and therapeutic strategies for MHE.In this commentary,we discussed a current issue of diagnostic tools for MHE,including neuropsychological tests.We also discussed the advantages of the other therapeutic strategies for MHE,such as intake of a regular breakfast and coffee,and supplementation with zinc and branched chain amino acids,on the MVA-related societal costs.

  1. Clinical features of hepatopulmonary syndrome in cirrhotic patients

    Institute of Scientific and Technical Information of China (English)

    Amir Houshang Mohammad Alizadeh; Mohammad Reza Zali; Seyed Reza Fatemi; Vahid Mirzaee; Manoochehr Khoshbaten; Bahman Talebipour; Afsaneh Sharifian; Ziba Khoram; Farhad Haj-sheikh-oleslami; Masoomeh Gholamreza-shirazi

    2006-01-01

    AIM: To evaluate the frequency, clinical and paraclinical features of hepatopulmonary syndrome (HPS) and to determine their predictive values in diagnosis of this syndrome in patients in Iran.METHODS: Fifty four cirrhotic patients underwent contrast enhanced echocardiography to detect intrapulmonary and intracardiac shunts by two cardiologists. Arterial blood oxygen, O2 gradient (A-a) and orthodoxy were measured by arterial blood gas (ABG) test. The patients positive for diagnostic criteria of HPS were defined as clinical HPS cases and those manifesting the intrapulmonary arterial dilation but no other criteria (arterial blood hypoxemia) were defined as IHPS cases. HPS frequency, sensitivity, positive and negative predictive values of clinical and paraclinical features were studied.RESULTS: Ten (18.5%) and seven (13%) cases had clinical and subclinical HPS, respectively. The most common etiology was hepatitis B. Dyspnea (100%) and cyanosis (90%) were the most prevalent clinical features. Dyspnea and clubbing were the most sensitive and specific clinical features respectively. No significant relationship was found between HPS and splenomegaly, ascites, edema, jaundice, oliguria, and collateral veins. HPS was more prevalent in hepatitis B. PaO2 30 and their sum, are the most valuable negative and positive predictive values in HPS patients.

  2. Acute predator stress impairs the consolidation and retrieval of hippocampus-dependent memory in male and female rats

    OpenAIRE

    Collin R Park; Zoladz, Phillip R.; Conrad, Cheryl D.; Fleshner, Monika; Diamond, David M

    2008-01-01

    We have studied the effects of an acute predator stress experience on spatial learning and memory in adult male and female Sprague-Dawley rats. All rats were trained to learn the location of a hidden escape platform in the radial-arm water maze (RAWM), a hippocampus-dependent spatial memory task. In the control (non-stress) condition, female rats were superior to the males in the accuracy and consistency of their spatial memory performance tested over multiple days of training. In the stress ...

  3. Neonatal Binge Alcohol Exposure Produces Dose Dependent Deficits in Interstimulus Interval Discrimination Eyeblink Conditioning in Juvenile Rats

    OpenAIRE

    Brown, Kevin L.; Burman, Michael A.; Duong, Huan B.; Stanton, Mark E.

    2008-01-01

    Alcohol consumption in neonatal rats produces cerebellar damage and is widely used to model 3rd-trimester human fetal alcohol exposure. Neonatal “binge-like” exposure to high doses of alcohol (5 g/kg/day or more) impairs acquisition of eyeblink classical conditioning (EBC), a cerebellar-dependent Pavlovian motor learning task. We have recently found impairments in interstimulus interval (ISI) discrimination – a complex task variant of EBC - in adult rats following postnatal day (PD) 4–9 alcoh...

  4. Effect of etomidate on voltage-dependent potassium currents in rat isolated hippocampal pyramidal neurons

    Institute of Scientific and Technical Information of China (English)

    TAN Hong-yu; SUN Li-na; WANG Xiao-liang; YE Tie-hu

    2010-01-01

    Background Previous studies demonstrated general anesthetics affect potassium ion channels, which may be one of the mechanisms of general anesthesia. Because the effect of etomidate on potassium channels in rat hippocampus which is involved in memory function has not been studied, we investigated the effects of etomidate on both delayed rectifier potassium current (I_((K(DR))) and transient outward potassium current (I_((K(A))) in acutely dissociated rat hippocampal pyramidal neurons.Methods Single rat hippocampal pyramidal neurons from male Wistar rats of 7-10 days were acutely dissociated by enzymatic digestion and mechanical dispersion according to the methods of Kay and Wong with slight modification. Voltage-clamp recordings were performed in the whole-cell patch clamp configuration. Currents were recorded with a List EPC-10 amplifier and data were stored in a computer using Pulse 8.5. Student's paired two-tail t test was used for data analysis. Results At the concentration of 100 μmol/L, etomidate significantly inhibited I_(K(DR)) by 49.2% at +40 mV when depolarized from -110 mV (P 0.05). The IC_(50) value of etomidate for blocking I_(K(DR)) was calculated as 5.4 μmol/L, with a Hill slope of 2.45. At the presence of 10 μmol/L etomidate, the V_(1/2) of activation curve was shifted from (17.3±1.5) mV to (10.7±9.9) mV (n=8, P <0.05), the V_(1/2) of inactivation curve was shifted from (-18.3±2.2) mV to (-45.3±9.4) mV (n=8, P <0.05). Etomidate 10 μmol/L shifted both the activation curve and inactivation curve of I_(K(DR)) to negative potential, but mainly affected the inactivation kinetics.Conclusions Etomidate potently inhibited I_(K(DR)) but not I_(K(A)) in rat hippocampal pyramidal neurons. I_(K(DR)) was inhibited by etomidate in a concentration-dependent manner, while I_(K(A)) remained unaffected.

  5. Vascular Endothelial Growth Factor And Soluble Adhesion Molecules As A Diagnostic Markers For Spontaneous Bacterial Peritonitis In Cirrhotic Liver Disease

    Directory of Open Access Journals (Sweden)

    Hamdia Ezzat Ahmed, (2Ahmed Dorrah,

    2006-03-01

    Full Text Available Spontaneous bacterial peritonitis (SBP is a frequent and severe complication in cirrhotic patients with ascites that usually results in renal failure and death despite the efficacy of the current antibiotic therapy. The aim of this study was determine serum and ascitic fluid of soluble-L selectin (s-L Selectin, intracellular adhesion molecule-1 (ICAM-1, Vascular cell adhesion molecule-1 (VCAM-1 and vascular endothelial growth factor (VEGF in cirrhotic patients, and to search for a relationship between them and SBP. This study was performed on 30 cirrhotic patients with SBP. Their ages ranged (from 38-55 years with mean of (32 + 5.5, 30 cirrhotic patients with non-infected ascites; their ages ranged (from 30-52 years with mean of (35 + 6.5. This group considered as cirrhotic control group and 20 healthy control subjects their ages ranged (from 28-55 years with mean of (30 + 7.5. Serum and ascitic fluid of adhesion molecules as well as VEGF levels were significantly higher in cirrhotic patients with SBP as well as cirrhotic patients with non-infected ascites as compared to healthy control group. There were significant increase in serum and ascitic fluid level of leukocyte, PMN and ICAM-1 in SBP as compared to cirrhotic with non-infected ascites. There was non-significant decrease in serum and AF level of VEGF in cirrhotic control group as compared to SBP group. The ascitic fluid PMN and s-L Selectin were higher in culture positive SBP patients particularly in those with gram positive isolates, where these are non-significant increase in serum and ascitic fluid level of VEGF in culture positive SBP than culture negative cases. Positive correlation was found between serum and ascitic fluid level of ICAM-1 in SBP and non-infected cirrhotic group. Also, positive correlation was found between VEGF levels in serum ascetic fluid levels in both cirrhotic groups (SBP and non-infected cirrhotic group. These data suggest that: Significant elevated level of

  6. In-hospital mortality among a cohort of cirrhotic patients admitted to a Tertiary Hospital

    Directory of Open Access Journals (Sweden)

    Mohammad A Alsultan

    2011-01-01

    Full Text Available Background/Aim : To determine the mortality rate in a cohort of hospitalized patients with cirrhosis and examine their resuscitation status at admission. Materials and Methods : A retrospective chart review was conducted of patients with cirrhosis who were admitted to a tertiary care hospital in Riyadh, Saudi Arabia, from January 1, 2009, to December 31, 2009. Results: We reviewed 226 cirrhotic patients during the study period. The hospital mortality rate was 35%. A univariate analysis revealed that worse outcomes were seen in patients with advanced age or who had worse child-turcotte-pugh (CPT scores, worse model for end-stage liver disease (MELD scores, low albumin and high serum creatinine. Using a multivariate analysis, we found that advanced age (P=0.004 and high MELD (P=0.001 scores were independent risk factors for the mortality of cirrhotic patients. The end-of-life decision were made in 34% of cirrhotic patients, and the majority of deceased patients were "no resuscitation" status (90% vs. 4%, P<0.001. Conclusions : The relatively high mortality in cirrhotic patients admitted for care in a tertiary hospital, Saudi Arabia was comparable to that reported in the literature. Furthermore, end-of-life discussions should be addressed early in the hospitalization of cirrhotic patients.

  7. Changes in serum ammonia concentration in cirrhotic patients with Helicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To study whether liver cirrhosis associated with Helicopacter pylori (H. pylori)infection will induce increased serum ammonia and whether the peripheral serum ammonia reflects the level of portal vein serum ammonia. Methods Blood was taken from the portal vein and the cubital vein in cirrhotic patients with and without H.pylori infection and non-cirrhotic patients (splenic rupiure) with and without H. pylori infection, and the serum ammonia was measured. Results The mean levels of serum ammonia in the group of cirrhotic patients with H. pylori infection were 167.82±8.97 μmol/L (pertal vein) and 142.2±13.35 μmol/L (cubital vein). They were increased significantly as compared with cirrhotic patients without H.pyiori infection(47.68±12.03 μmol/L portal vein and 37.23±7.04 μmol/L cubital vein),and also compared with the groups of splenic rupture patients with and without H. pylori infection (P<0.0t).There was no significant difference between the serum ammonia level of the cubital vein and pertal vein(P>0.05). Conclusions H.pylori intection can induce an increase in serum ammonia in patients with liver dysfunction,and the peripheral serum ammonia measurement may replace the portal vein serum ammania as a monitoring method. Eradication of H.pylori in cirrhotic patients may prevent hepatic encephalopathy(HE).

  8. EXHALED AND PLASMA NITRITE: a comparative study among healthy, cirrhotic and liver transplant patients

    Directory of Open Access Journals (Sweden)

    Viviane S AUGUSTO

    2014-03-01

    Full Text Available Context There is a relative lack of studies about exhaled nitrite (NO2- concentrations in cirrhotic and transplanted patients. Objective Verify possible differences and correlations between the levels of NO2-, measured in plasma and exhaled breath condensate collected from patients with cirrhosis and liver transplant. Method Sixty adult male patients, aged between 27 and 67 years, were subdivided into three groups: a control group comprised of 15 healthy volunteers, a cirrhosis group composed of 15 volunteers, and a transplant group comprised of 30 volunteers. The NO2- concentrations were measured by chemiluminescence. Results 1 The analysis of plasma NO2- held among the three groups showed no statistical significance. 2 The comparison between cirrhotic and control groups, control and transplanted and cirrhotic and transplanted was not statistically significant. 3 The measurements performed on of NO2- exhaled breath condensate among the three groups showed no statistical difference. 4 When comparing the control group samples and cirrhotic, control and transplanted and cirrhotic and transplanted, there was no significant changes in the concentrations of NO2-. Conclusion No correlations were found between plasma and exhaled NO2-, suggesting that the exhaled NO2- is more reflective of local respiratory NO release than the systemic circulation.

  9. Use-dependent learning and memory of the Hering-Breuer inflation reflex in rats.

    Science.gov (United States)

    MacDonald, Shawna M; Tin, Chung; Song, Gang; Poon, Chi-Sang

    2009-02-01

    The classic Hering-Breuer inflation reflex (HBIR) is a widely held tenet for understanding the lung volume-related vagal control of respiratory rhythm. Recent evidence, however, has revealed that the fictive HBIR elicited by electrical vagal stimulation in rats is not static but may be attenuated centrally by two forms of non-associative learning (habituation and desensitization) that continually mitigate the reflex effects with exponential adaptations like a differentiator or high-pass filter. Desensitization is analogous to habituation but exhibits an explicit short-term memory (STM) in the form of a rebound response with exponential decay during recovery from stimulation. To investigate whether such learning and memory effects are lung volume related and use-dependent (practice makes perfect), we compared the time-dependent changes in inspiratory and expiratory durations (t(I) and t(E)) during and after 1 or 8 min unilateral lung inflation or high-frequency, low-intensity vagal stimulation in anaesthetized, uni- or bi-vagotomized rats. Unilateral lung inflation and vagal stimulation both elicited abrupt shortening of t(I) and lengthening of t(E) (HBIR effects) and gradual habituation and desensitization throughout the 1 or 8 min test period, followed by rebound responses in t(I) and t(E) with exponential recovery (STM effects) in the post-test period. In both cases, the STM time constants for t(I) and t(E) were significantly longer with the 8 min test than with the 1 min test (17-45 versus 4-11 s, P < 0.01). We conclude that the HBIR and its central habituation and desensitization are mediated peripherally by lung volume-related vagal afferents, and that the STM of desensitization is use-dependent. The translational implications of these findings are discussed. PMID:19028808

  10. Dietary modulation of rat colonic cAMP-dependent protein kinase activity.

    Science.gov (United States)

    Aukema, H M; Davidson, L A; Chang, W C; Lupton, J R; Derr, J N; Chapkin, R S

    1994-10-20

    Malignant transformation of cells is associated with enhanced proliferation and alterations in cAMP-dependent protein kinase (PKA) activity. To investigate the role of PKA in normal colonic cell proliferation, PKA was characterized in rat colonic mucosa. In addition, rats were fed diets containing different fats (corn oil, fish oil) and fibers (pectin, cellulose, fiber free) to elicit varying levels of colonic cell proliferation in order to study this signaling system under normal physiologic conditions. Overall, PKA activities were higher in cytosolic compared to membrane fractions. PKA type II (PKA II) isozyme contributed 89 +/- 1% and 96 +/- 1% of total PKA activity in cytosolic and membrane fractions, respectively. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed the presence of mRNA for both the alpha and beta isoforms of the regulatory subunits of PKA II. PKA activities were 21-33% higher in distal membrane and total distal fractions in rats fed a cellulose/corn oil diet compared to animals consuming the other fiber/fat diets. These effects were seen only in the distal colon, where the number of cells per crypt column was elevated only in animals fed the cellulose/corn oil diet relative to other diets. Diet-induced mitogenic responses did not involve significant changes in the relative activity of PKA I and II isozymes. These data demonstrate that dietary effects on PKA activity in the distal colon may be related to changes in cell differentiation as indicated by the number of cells per crypt column. PMID:7948042

  11. The carotid body of the spontaneous insulin-dependent diabetic rat

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    Clarke J.A.

    1999-01-01

    Full Text Available The carotid bodies from adult spontaneous insulin-dependent diabetic rats (strain BB/S were perfusion-fixed at normal arterial blood pressure with 3% phosphate-buffered glutaraldehyde and compared with the organs from control rats (strain BB/Sc prepared in the same way. Serial 5-µm sections were cut, stained, and using an interactive image analysis system, were analysed to determine the volumes of the carotid body and its vascular and extravascular compartments. There was no evidence of systemic arterial disease in the carotid stem arteries in either group of animals, and the microvasculature of the organs appeared normal by light microscopy. The volume of the carotid body was unchanged 3 months after the onset of diabetes but was increased at 6 months. The total vascular volume of the organ was unchanged, but the volume of the small vessels (5-12 µm was increased. In the control group the small vessels comprised 5% of the total volume of the carotid body, or about 44% of the vascular compartment. The percentage of small vessels increased at 3 months in the diabetic group, but had returned to normal at 6 months. The extravascular volume followed the same pattern as the total carotid body volume and so did not change appreciably when expressed as a percentage of the total volume of the organ. The increase in size of the carotid body in diabetic rats is due, therefore, to an augmented extravascular volume. In one diabetic specimen the carotid sinus nerve showed signs of diabetic neuropathy, axonal swelling and intramyelinic oedema. The clinical implications of these results are discussed.

  12. Hesperidin alleviates rat postoperative ileus through anti-inflammation and stimulation of Ca2+-dependent myosin phosphorylation

    Science.gov (United States)

    Xiong, Yong-jian; Chu, Hong-wei; Lin, Yuan; Han, Fang; Li, Ya-chan; Wang, Ai-guo; Wang, Fu-jin; Chen, Da-peng; Wang, Jing-yu

    2016-01-01

    Aim: Postoperative ileus (POI) is a postoperative dysmotility disorder of gastrointestinal tract, which remains one of the most perplexing problems in medicine. In the present study we investigated the effects of hesperidin, a major flavonoid in sweet oranges and lemons, on POI in rats. Methods: SD rats were administered hesperidin (5, 20, and 80 mg·kg−1·d−1, ig) for 3 consecutive days. POI operation (gently manipulating the cecum for 1 min) was performed on d 2. The gastrointestinal motility and isolated intestinal contraction were examined 1 d after the operation. Then the myosin phosphorylation and inflammatory responses in cecum tissue were assessed. Smooth muscle cells were isolated from rat small intestine for in vitro experiments. Results: The gastric emptying and intestinal transit were significantly decreased in POI rats, which were reversed by administration of hesperidin. In ileum and cecum preparations of POI rats in vitro, hesperidin (2.5–160 μmol/L) dose-dependently increased the spontaneous contraction amplitudes without affecting the contractile frequency, which was blocked by the myosin light chain kinase (MLCK) inhibitor ML-7 or verapamil, but not by TTX. Furthermore, administration of hesperidin increased the phosphorylation of MLC20 in the cecum tissue of POI rats. Moreover, administration of hesperidin reversed the increased levels of inflammatory cytokines, iNOS and COX-2 in cecum tissue of POI rats. In freshly isolated intestinal smooth muscle cells, hesperidin (5–80 μmol/L) dose-dependently increased the intracellular Ca2+ concentration as well as the phosphorylation of MLC20, which was abrogated by ML-7 or siRNA that knocked down MLCK. Conclusion: Oral administration of hesperidin effectively alleviates rat POI through inhibition of inflammatory responses and stimulation of Ca2+-dependent MLC phosphorylation. PMID:27345626

  13. Vitamin D-dependent rat renal calcium-binding protein: development of a radioimmunoassay, tissue distribution, and immunologic identification

    International Nuclear Information System (INIS)

    A sensitive double antibody RIA has been developed for the 28,000 mol wt rat renal vitamin D-dependent calcium-binding protein. Using this assay, concentrations of calcium-binding protein (CaBP) as low as 30 ng can be measured. The assay is precise (intraassay variability, 5.0%) and reproductible (interassay variability, 8.2%). Measurements of renal CaBP by RIA showed a good correlation with measurements of CaBP by the chelex resin assay and by polyacrylamide gel analysis by densitometric tracing using a purified CaBP marker. The concentration of CaBP in the vitamin D-replete rat kidney is 7.3 +/- 1.0 (mean +/- SEM) micrograms/mg protein. In vitamin D-deficient rats the level of renal CaBP is 2.6 +/- 0.3 micrograms/mg protein. Tissue distribution of immunoreactive rat renal CaBP showed the highest concentration of CaBP in the rat cerebellum (38.3 +/- 5.1 micrograms/mg protein). Lower concentrations of immunoreactive CaBP were detected in several other rat tissues. No immunoreactive CaBP was detected in rat or human serum. In necropsy human kidney and cerebellum, high levels of immunoreactive CaBP were also detected (1.5 +/- 0.1 and 27.3 +/- 2.1 micrograms/mg protein, respectively). When extracts of rat kidney and brain and human cerebellum and kidney were assayed at several dilutions, immunodisplacement curves parallel to that of pure renal CaBP were observed, indicating immunochemical similarity. Fractionation of extracts of rat cerebellum, human kidney, and human cerebellum on Sephadex G-100 revealed immunoreactivity and calcium-binding activity in the 28,000 mol wt region similar to rat kidney

  14. Elements in normal and cirrhotic human liver. Potassium, iron, copper, zinc and bromine measured by X-ray fluorescence spectrometry

    DEFF Research Database (Denmark)

    Laursen, J.; Milman, N.; Leth, Peter Mygind;

    1990-01-01

    Various elements (K, Fe, Cu, Zn, Br) were measured by X-ray flourescence spectrometry in cellular and connective tissue fractions of normal and cirrhotic liver samples obtained at autopsy. Normal livers: 32 subjects (16 males, 16 females) median age 69 years. Cirrhotic livers: 14 subjects (13 mal...

  15. Hormone-dependent aggression in female rats: testosterone implants attenuate the decline in aggression following ovariectomy.

    Science.gov (United States)

    Albert, D J; Jonik, R H; Walsh, M L

    1990-04-01

    Female rats were individually housed with a sterile male for a 4- to 5-week period. Each female was then tested for aggression toward an unfamiliar female intruder at weekly intervals. Those females that displayed a high level of aggression on each of three weekly tests were ovariectomized and given subcutaneous implants of testosterone-filled tubes, ovariectomized and given subcutaneous implants of empty tubes, or sham-ovariectomized and implanted with empty tubes. These implants should produce a serum testosterone concentration of about 0.6 ng/ml, compared to 0.17 ng/ml in intact females. Beginning 1 week postoperatively, the aggression of each female was tested weekly for 4 weeks. Ovariectomized females with testosterone implants displayed a level of aggression significantly higher than that of ovariectomized females with empty implants on 3 of 4 weekly tests. The level of aggression by females with testosterone implants was not significantly different from that of sham-ovariectomized females on the first postoperative test. Additional observations showed that testosterone implants did not produce an increase in aggression in females whose preoperative level of aggression was low. Further, Silastic implants containing estrogen (1 to 2 mm long) sufficient to maintain a serum estrogen level of 20 to 30 pg/ml also attenuated the decline of aggression following ovariectomy. These results suggest that testosterone and estrogen may both contribute to the biological substrate of hormone-dependent aggression in female rats.

  16. Ferutinin dose-dependent effects on uterus and mammary gland in ovariectomized rats.

    Science.gov (United States)

    Ferretti, Marzia; Cavani, Francesco; Manni, Paola; Carnevale, Gianluca; Bertoni, Laura; Zavatti, Manuela; Palumbo, Carla

    2014-08-01

    The present paper completes our recent study on the effects of phytoestrogen ferutinin in preventing osteoporosis and demonstrating the superior osteoprotective effect of a 2 mg/kg/day dose in ovariectomized (OVX) rats, compared to both estrogens and lower (0.5, 1 mg/kg/day) ferutinin doses. Morphological and morphometrical analyses were performed on the effects of different doses of ferutinin administrated for one month on uterus and on mammary gland of Sprague-Dawley OVX rats, evaluated in comparison with the results for estradiol benzoate. To verify whether ferutinin provides protection against uterine and breast cancer, estimations were made of both the amount of cell proliferation (by Ki-67), and the occurrence of apoptosis (by TUNEL), two processes that in unbalanced ratio form the basis for cancer onset. The results suggest that the effects of ferutinin are dose dependent and that a 2 mg/kg/day dose might offer a better protective action against the onset of both breast and uterine carcinoma compared to ferutinin in lower doses or estradiol benzoate, increasing cellular apoptosis in glandular epithelia. PMID:24510547

  17. Proteomic identification of age-dependent protein nitration in rat skeletal muscle.

    Science.gov (United States)

    Kanski, Jaroslaw; Alterman, Michail A; Schöneich, Christian

    2003-11-15

    Age-related protein nitration was studied in skeletal muscle of Fisher 344 and Fisher 344/Brown Norway (BN) F1 rats by a proteomic approach. Proteins from young (4 months) and old (24 months) Fisher 344 rats and young (6 months) and old (34 months) Fisher 344/BN F1 animals were separated by 2-D gel electrophoresis. Western blot showed an age-related increase in the nitration of a few specific proteins, which were identified by MALDI-TOF MS and ESI-MS/MS. We identified age-dependent apparent nitration of beta-enolase, alpha-fructose aldolase, and creatine kinase, which perform important functions in muscle energy metabolism, suggesting that the nitration of such key proteins can be, in part, responsible for the decline of muscle motor function of the muscle. Furthermore, we have identified the apparent nitration of succinate dehydrogenase, rab GDP dissociation inhibitor beta (GdI-2), triosephosphate isomerase, troponin I, alpha-crystallin, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH).

  18. Treadmill exercise induces age and protocol-dependent epigenetic changes in prefrontal cortex of Wistar rats.

    Science.gov (United States)

    Cechinel, Laura Reck; Basso, Carla Giovana; Bertoldi, Karine; Schallenberger, Bruna; de Meireles, Louisiana Carolina Ferreira; Siqueira, Ionara Rodrigues

    2016-10-15

    Some studies have linked age-related beneficial effects of exercise and epigenetic mechanisms. Although, the impact of treadmill exercise on histone acetylation, histone and DNA methylation marks in aged cortices yet remains poorly understood. Considering the role of frontal cortex on brain functions, we investigated the potential of different exercise protocols, single session and daily exercise, to modulate epigenetic marks, namely global H4 acetylation, histone methyltransferase activity (HMT H3K27) and levels of DNA methytransferase (DNMT1 and DNMT3b) in prefrontal cortices from 3 and 21-months aged Wistar rats. The animals were submitted to two treadmill exercise protocols, single session (20min) or daily moderate (20min/day during 14days). The daily exercise protocol induced an increased in histone H4 acetylation levels in prefrontal cortices of 21-months-old rats, without any effects in young adult group. DNMT3b levels were increased in aged cortices of animals submitted to single session of exercise. These results indicate that prefrontal cortex is susceptible to epigenetic changes in a protocol dependent-manner and that H4 acetylation levels and DNMT3b content changes might be linked at least in part to exercise-induced effects on brain functions. PMID:27418438

  19. Reduced motivation in the BACHD rat model of Huntington disease is dependent on the choice of food deprivation strategy.

    Directory of Open Access Journals (Sweden)

    Erik Karl Håkan Jansson

    Full Text Available Huntington disease (HD is an inherited neurodegenerative disease characterized by motor, cognitive, psychiatric and metabolic symptoms. Animal models of HD show phenotypes that can be divided into similar categories, with the metabolic phenotype of certain models being characterized by obesity. Although interesting in terms of modeling metabolic symptoms of HD, the obesity phenotype can be problematic as it might confound the results of certain behavioral tests. This concerns the assessment of cognitive function in particular, as tests for such phenotypes are often based on food depriving the animals and having them perform tasks for food rewards. The BACHD rat is a recently established animal model of HD, and in order to ensure that behavioral characterization of these rats is done in a reliable way, a basic understanding of their physiology is needed. Here, we show that BACHD rats are obese and suffer from discrete developmental deficits. When assessing the motivation to lever push for a food reward, BACHD rats were found to be less motivated than wild type rats, although this phenotype was dependent on the food deprivation strategy. Specifically, the phenotype was present when rats of both genotypes were deprived to 85% of their respective free-feeding body weight, but not when deprivation levels were adjusted in order to match the rats' apparent hunger levels. The study emphasizes the importance of considering metabolic abnormalities as a confounding factor when performing behavioral characterization of HD animal models.

  20. Dose-Related and Time-Dependent Development of Collagenase-Induced Tendinopathy in Rats

    Science.gov (United States)

    Viganò, Marco; Stanco, Deborah; Bottagisio, Marta; Di Giancamillo, Alessia; Setti, Stefania; de Girolamo, Laura

    2016-01-01

    Tendinopathy is a big burden in clinics and it represents 45% of musculoskeletal lesions. Despite the relevant social impact, both pathogenesis and development of the tendinopathy are still under-investigated, thus limiting the therapeutic advancement in this field. The purpose of this study was to evaluate the dose-dependent and time-related tissue-level changes occurring in a collagenase-induced tendinopathy in rat Achilles tendons, in order to establish a standardized model for future pre-clinical studies. With this purpose, 40 Sprague Dawley rats were randomly divided into two groups, treated by injecting collagenase type I within the Achilles tendon at 1 mg/mL (low dose) or 3 mg/mL (high dose). Tendon explants were histologically evaluated at 3, 7, 15, 30 and 45 days. Our results revealed that both the collagenase doses induced a disorganization of collagen fibers and increased the number of rounded resident cells. In particular, the high dose treatment determined a greater neovascularization and fatty degeneration with respect to the lower dose. These changes were found to be time-dependent and to resemble the features of human tendinopathy. Indeed, in our series, the acute phase occurred from day 3 to day 15, and then progressed towards the proliferative phase from day 30 to day 45 displaying a degenerative appearance associated with a very precocious and mild remodeling process. The model represents a good balance between similarity with histological features of human tendinopathy and feasibility, in terms of tendon size to create lesions and costs when compared to other animal models. Moreover, this model could contribute to improve the knowledge in this field, and it could be useful to properly design further pre-clinical studies to test innovative treatments for tendinopathy. PMID:27548063

  1. Spatial and activity-dependent catecholamine release in rat adrenal medulla under native neuronal stimulation.

    Science.gov (United States)

    Wolf, Kyle; Zarkua, Georgy; Chan, Shyue-An; Sridhar, Arun; Smith, Corey

    2016-09-01

    Neuroendocrine chromaffin cells of the adrenal medulla in rat receive excitatory synaptic input through anterior and posterior divisions of the sympathetic splanchnic nerve. Upon synaptic stimulation, the adrenal medulla releases the catecholamines, epinephrine, and norepinephrine into the suprarenal vein for circulation throughout the body. Under sympathetic tone, catecholamine release is modest. However, upon activation of the sympathoadrenal stress reflex, and increased splanchnic firing, adrenal catecholamine output increases dramatically. Moreover, specific stressors can preferentially increase release of either epinephrine (i.e., hypoglycemia) or norepinephrine (i.e., cold stress). The mechanism for this stressor-dependent segregated release of catecholamine species is not yet fully understood. We tested the hypothesis that stimulation of either division of the splanchnic selects for epinephrine over norepinephrine release. We introduce an ex vivo rat preparation that maintains native splanchnic innervation of the adrenal gland and we document experimental advantages and limitations of this preparation. We utilize fast scanning cyclic voltammetry to detect release of both epinephrine and norepinephrine from the adrenal medulla, and report that epinephrine and norepinephrine release are regulated spatially and in a frequency-dependent manner. We provide data to show that epinephrine is secreted preferentially from the periphery of the medulla and exhibits a higher threshold and steeper stimulus-secretion function than norepinephrine. Elevated stimulation of the whole nerve specifically enhances epinephrine release from the peripheral medulla. Our data further show that elimination of either division from stimulation greatly attenuated epinephrine release under elevated stimulation, while either division alone can largely support norepinephrine release. PMID:27597763

  2. Clinical utility of breath ammonia for evaluation of ammonia physiology in healthy and cirrhotic adults.

    Science.gov (United States)

    Spacek, Lisa A; Mudalel, Matthew; Tittel, Frank; Risby, Terence H; Solga, Steven F

    2015-12-01

    Blood ammonia is routinely used in clinical settings to assess systemic ammonia in hepatic encephalopathy and urea cycle disorders. Despite its drawbacks, blood measurement is often used as a comparator in breath studies because it is a standard clinical test. We sought to evaluate sources of measurement error and potential clinical utility of breath ammonia compared to blood ammonia. We measured breath ammonia in real time by quartz enhanced photoacoustic spectrometry and blood ammonia in 10 healthy and 10 cirrhotic participants. Each participant contributed 5 breath samples and blood for ammonia measurement within 1 h. We calculated the coefficient of variation (CV) for 5 breath ammonia values, reported medians of healthy and cirrhotic participants, and used scatterplots to display breath and blood ammonia. For healthy participants, mean age was 22 years (±4), 70% were men, and body mass index (BMI) was 27 (±5). For cirrhotic participants, mean age was 61 years (±8), 60% were men, and BMI was 31 (±7). Median blood ammonia for healthy participants was within normal range, 10 μmol L(-1) (interquartile range (IQR), 3-18) versus 46 μmol L(-1) (IQR, 23-66) for cirrhotic participants. Median breath ammonia was 379 pmol mL(-1) CO2 (IQR, 265-765) for healthy versus 350 pmol mL(-1) CO2 (IQR, 180-1013) for cirrhotic participants. CV was 17  ±  6%. There remains an important unmet need in the evaluation of systemic ammonia, and breath measurement continues to demonstrate promise to fulfill this need. Given the many differences between breath and blood ammonia measurement, we examined biological explanations for our findings in healthy and cirrhotic participants. We conclude that based upon these preliminary data breath may offer clinically important information this is not provided by blood ammonia.

  3. The thalamus in cirrhotic patients with and without hepatic encephalopathy: A volumetric MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Ran, E-mail: taoran1648@yahoo.cn [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Department of Radiology, Bethune International Peace Hospital of People' s Liberty Army, Shijiazhuang 050082, Hebei Province (China); Zhang, Jiuquan, E-mail: jiuquanzhang@yahoo.com [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); You, Zhonglan, E-mail: you_zhonglan@163.com [Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Wei, Luqing, E-mail: weiluqing@foxmail.com [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Fan, Yi, E-mail: fanyi1978@yahoo.cn [Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Cui, Jinguo, E-mail: cuijinguo2005@163.com [Department of Radiology, Bethune International Peace Hospital of People' s Liberty Army, Shijiazhuang 050082, Hebei Province (China); Wang, Jian, E-mail: wangjian_811@yahoo.com [Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China)

    2013-11-01

    Background and aims: The thalamus is a major relay and filter station in the central neural system. Some previous studies have suggested that the thalamus maybe implicated in the pathogenesis of hepatic encephalopathy. The aim of our study was to investigate changing thalamic volumes in cirrhotic patients with and without hepatic encephalopathy. Methods: Neuropsychological tests and structural MR scanning were performed on 24 cirrhotic patients, 23 cirrhotic patients with minimal hepatic encephalopathy, 24 cirrhotic patients during their first episode of overt hepatic encephalopathy, and 33 healthy controls. Voxel-based morphometry analysis was performed to detect gray matter morphological changes. The thalamus and whole brain volume were extrapolated. A receiver operating characteristic curve analysis of thalamic volumes was used to discriminate patients with minimal hepatic encephalopathy from those with hepatic cirrhosis. Results: Thalamic volume increased in a stepwise manner in patients with progressively worse stages of hepatic encephalopathy compared to healthy subjects. Additionally, a comparison of gray matter morphometry between patients with Child–Pugh grades A, B, or C and controls revealed a progression in thalamic volumes in parallel with the degree of liver failure. Moreover, thalamic volume was significantly correlated with the number connection test A time and digit-symbol test score in cirrhotic patients with minimal hepatic encephalopathy (r = 0.659, P = 0.001; r = −0.577, P = 0.004; respectively). The area under the receiver operating characteristic curve was 0.827 (P = 0.001). Conclusions: A significantly increased thalamic volume may be provide an objective imaging measure for predicting seizures due to minimal hepatic encephalopathy in cirrhotic patients.

  4. Peritoneal Dialysis is Associated With A Better Survival in Cirrhotic Patients With Chronic Kidney Disease.

    Science.gov (United States)

    Chou, Che-Yi; Wang, Shu-Ming; Liang, Chih-Chia; Chang, Chiz-Tzung; Liu, Jiung-Hsiun; Wang, I-Kuan; Hsiao, Lien-Cheng; Muo, Chih-Hsin; Chung, Chi-Jung; Huang, Chiu-Ching

    2016-01-01

    Peritoneal dialysis (PD) can be an ideal treatment in cirrhotic patients with ascites and chronic kidney disease stage 5 (CKD 5D) who require dialysis. The survival of cirrhotic patients with CKD 5D on PD, however, is not clear. We compared the survival of cirrhotic patients with CKD 5D on PD and the survival of those on HD. Two datasets including a cohort study of China Medical University Hospital (CMUH) from 2004 to 2013 and the Longitudinal National Health Insurance Database for Catastrophic Illness Patients (LHID-CIP) of Taiwan from 1996 to 2011 were analyzed. The survival of cirrhotic patients on PD and the propensity score matched cirrhotic patients on HD were analyzed using Cox proportional hazards regression. In CMUH cohort of 85 PD and 340 HD patients, the all-cause mortality was lower in PD patients compared to it in HD patients (hazard ratio [HR]: 0.48, 95% confidence interval [CI]: 0.31-0.74, P model for end-stage liver disease (MELD) score, however, was not associated with all-cause mortality. In the LHID-CIP cohort of 285 PD and 1140 HD patients, the HR of all-cause mortality in PD patients was 0.61 (95% CI: 0.47 - 0.79, P < 0.01), as compared with HD patients. PD in cirrhotic patients who need dialysis is associated with lower all-cause mortality than HD is. This association is independent of patients' comorbidity, severity of liver cirrhosis, and serum albumin levels.

  5. Renal effects of the novel selective adenosine A1 receptor blocker SLV329 in experimental liver cirrhosis in rats.

    Directory of Open Access Journals (Sweden)

    Berthold Hocher

    Full Text Available Liver cirrhosis is often complicated by an impaired renal excretion of water and sodium. Diuretics tend to further deteriorate renal function. It is unknown whether chronic selective adenosine A(1 receptor blockade, via inhibition of the hepatorenal reflex and the tubuloglomerular feedback, might exert diuretic and natriuretic effects without a reduction of the glomerular filtration rate. In healthy animals intravenous treatment with the novel A(1 receptor antagonist SLV329 resulted in a strong dose-dependent diuretic (up to 3.4-fold and natriuretic (up to 13.5-fold effect without affecting creatinine clearance. Male Wistar rats with thioacetamide-induced liver cirrhosis received SLV329, vehicle or furosemide for 12 weeks. The creatinine clearance of cirrhotic animals decreased significantly (-36.5%, p<0.05, especially in those receiving furosemide (-41.9%, p<0.01. SLV329 was able to prevent this decline of creatinine clearance. Mortality was significantly lower in cirrhotic animals treated with SLV329 in comparison to animals treated with furosemide (17% vs. 54%, p<0.05. SLV329 did not relevantly influence the degree of liver fibrosis, kidney histology or expression of hepatic or renal adenosine receptors. In conclusion, chronic treatment with SLV329 prevented the decrease of creatinine clearance in a rat model of liver cirrhosis. Further studies will have to establish whether adenosine A(1 receptor antagonists are clinically beneficial at different stages of liver cirrhosis.

  6. Sex differences in alcohol consumption and alterations in nucleus accumbens endocannabinoid mRNA in alcohol-dependent rats.

    Science.gov (United States)

    Henricks, Angela M; Berger, Anthony L; Lugo, Janelle M; Baxter-Potter, Lydia N; Bieniasz, Kennedy V; Craft, Rebecca M; McLaughlin, Ryan J

    2016-10-29

    Chronic intermittent alcohol (CIA) exposure produces altered motivational states characterized by anxiety and escalated alcohol consumption during withdrawal. The endocannabinoid (ECB) system contributes to these symptoms, and sex differences in alcohol dependence, as well as bidirectional interactions between ECBs and gonadal hormones have been documented. Thus, we evaluated sex differences in alcohol consumption, anxiety-like behavior, and ECB mRNA expression in the nucleus accumbens (NAc) of alcohol-dependent rats during acute withdrawal. Male rats exposed to six weeks of CIA showed escalated alcohol consumption during acute withdrawal and reductions in NAc N-acyl phosphatidylethanolamine phospholipase D (NAPEPLD), DAG lipase alpha (DAGLα), and monoacylglycerol lipase (MAGL) mRNA. Intact alcohol-dependent female rats also escalated their consumption, but notably, this effect was also present in non-dependent females. No differences in NAc ECB mRNA were observed between CIA- and air-exposed females during acute withdrawal. However, when these data were analyzed according to estrous stage, significant differences in NAPEPLD and MAGL mRNA expression emerged in the NAc of air-exposed control rats, which were absent in alcohol-dependent females. We subsequently measured alcohol consumption and NAc ECB mRNA in ovariectomized (OVX) females with or without estradiol (E2) replacement during withdrawal. Neither E2 nor CIA altered alcohol consumption in OVX females. However, E2 reduced both DAGLα and MAGL mRNA, suggesting that E2 may influence the biosynthesis and degradation of 2-arachidonoylglycerol (2-AG) in the NAc. Collectively, these studies indicate sexual dimorphism in alcohol consumption in non-dependent rats and suggest that E2-mediated alterations in NAc ECB mRNA expression during withdrawal may be a mechanism by which sex differences in alcohol dependence emerge. PMID:27578612

  7. Serum neutral amino acid concentrations in cirrhotic patients with impaired carbohydrate metabolism.

    Directory of Open Access Journals (Sweden)

    Watanabe,Akiharu

    1983-08-01

    Full Text Available Serum neutral amino acid levels in cirrhotic patients with abnormal oral glucose tolerance test patterns were not different from those of subjects without impaired carbohydrate metabolism. However, the characteristic features of serum aminograms in the patients, that is, increased levels of tyrosine, decreased levels of valine and leucine and the diminished ratio of branched chain amino acids to phenylalanine and tyrosine levels, were less pronounced in those treated with insulin. This finding is clinically important for evaluating the serum aminogram of cirrhotic patients under insulin therapy.

  8. Hepatocellular carcinoma arising from hepatocellular adenoma in a hepatitis B virus-associated cirrhotic liver

    Energy Technology Data Exchange (ETDEWEB)

    Seo, J.M. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lee, S.J., E-mail: lucia@skku.edu [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, S.H. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Park, C.K.; Ha, S.Y. [Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2012-04-15

    Hepatocellular adenoma (HCA) is a rare, benign proliferation of hepatocytes that occurs mostly in a normal liver and in extreme rare cases, occurs in a cirrhotic liver. Hepatocellular carcinomas (HCC) arising within HCA through malignant transformation is rare. The specific incidence and mechanism of malignant transformation has not been established, but the long term use of oral contraceptives is considered a causative agent. We report a case of HCC arising from HCA detected in a hepatitis B-related cirrhotic liver with serial radiologic images.

  9. Expression patterns of cytokine, growth factor and cell cycle-related genes after partial hepatectomy in rats with thioacetamide-induced cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Shu Yang; Chon Kar Leow; Theresa May Chin Tan

    2006-01-01

    AIM: To examine the differences in the responses of normal and cirrhotic livers to partial hepatectomy in relation to the factors influencing liver regeneration.METHODS: Cirrhosis was induced in rats by administration of thioacetamide. Untreated rats were used as controls. The control rats as well as the cirrhotic rats were subjected to 70% partial hepatectomy. At different time points after hepatectomy, the livers were collected and the levels of cytokines, growth factors and cell cycle proteins were analyzed.RESULTS: After hepatectomy, the cirrhotic remnant expressed significantly lower levels of cyclin D1, its kinase partner, cdk4, and cyclin E as compared to the controls up to 72 h post hepatectomy. Significantly lower levels of cydin A and cdk2 were also observed while the cdk inhibitor, p27 was significantly higher. In addition,the cirrhotic group had lower IL-6 levels than the control group at all time points up to 72 h following resection.CONCLUSION: The data from our study shows that impaired liver regeneration in cirrhotic remnants is associated with low expression of cyclins and cdks.This might be the consequence of the low IL-6 levels in cirrhotic liver remnant which would in turn influence the actions of transcription factors that regulate genes involved in cell proliferation and metabolic homeostasis during the regeneration process.

  10. Two isoforms of cyclooxygenase contribute to augmented endothelium-dependent contractions in femoral arteries of 1-year-old rats

    Institute of Scientific and Technical Information of China (English)

    Yi SHI; Ricky YK MAN; Paul M VANHOUTTE

    2008-01-01

    Aim: The present experiments were designed to study the changes in endothe-lium-dependent contractions with aging. Methods: The rat femoral arteries of 20-week and 1-year-old rats with and without endothelium were suspended in organ chambers to record isometric tension. The production of oxygen-derived free radicals in the endothelium was measured with 2',7'-dichiorodihydrofluorescein diacetate (DCF) using confocal microscopy. Protein presences were determined by Western blotting. Results: In the arteries from the 1-year-old rats, endothe-lium-dependent relaxations to A23187 were reduced, but the endothelium-depen-dent contractions to A23187 (in the presence of Nω-nitro-L-arginine methyl ester hydrochloride [L-NAME; an inhibitor of nitric oxide synthase]) were augmented, demonstrating endothelial dysfunction with aging. Indomethacin normalized the responses, suggesting that a cyclooxygenase (COX)-dependent contraction is prominent in aging. The endothelium-dependent contractions were also prevented by terntroban (a blocker of thromboxane-prostanoid receptors), confirming the activation of thromboxane-prostanoid receptors on vascular smooth muscle. Valeryl salicylate and NS-398 (preferential inhibitors of COX-1 and COX-2, respectively) partially reduced the response, indicating that both COX-1 and COX-2 are involved. Western blotting confirmed the upregulation of both isoforms in the arteries of the 1-year-old rats. In the presence of L-NAME, A23187 increased the DCF fluores-cence in the endothelium, demonstrating that the production of oxygen-derived free radicals contributes to endothelium-dependent contractions. The activity of catalase was reduced in the arteries with endothelium of 1-year-old rats, indicating that hydrogen peroxide is the likely mediator of increased oxidative stress in the aging endothelium. Conclusion: Endothelium-dependent contractions are aug-mented with aging. Oxidative stress potentiates the response, and both COX-1 and COX-2 are

  11. TNF-A Levels throughout the Critical Period for Experience-Dependent Plasticity in the Rat Primary Auditory Cortex

    NARCIS (Netherlands)

    Man, WH; Madeira, Caroline; Zhou, Xiaoming; Merzenich, Michael M; Panizzutti, Rogerio

    2015-01-01

    Tumor necrosis factor- alpha (TNF-α) is likely to play a role in brain plasticity. To determine whether TNF-α levels change throughout a critical period of experience-dependent brain plasticity, we assessed these levels in the primary auditory cortex of rats before, during and after the critical per

  12. TIME-DEPENDENT EFFECTS ON GENE EXPRESSION IN RAT SEMINAL VESICLE DEVELOPMENTALLY ALTERED BY IN UTERO EXPOSURE TO TCDD

    Science.gov (United States)

    TIME-DEPENDENT EFFECTS ON GENE EXPRESSION IN RAT SEMINAL VESICLE DEVELOPMENTALLY ALTERED BY IN UTERO EXPOSURE TO TCDD. V M Richardson', J T Hamm2, and L S Birnbaum1. 'USEPA, ORD/NHEERL/ETD, Research Triangle Park, NC, USA, 'Curriculum in Toxicology, University of North Carolina, ...

  13. RASSF1A and DOK1 Promoter Methylation Levels in Hepatocellular Carcinoma, Cirrhotic and Non-Cirrhotic Liver, and Correlation with Liver Cancer in Brazilian Patients

    Science.gov (United States)

    Araújo, Oscar C.; Rosa, Agatha S.; Fernandes, Arlete; Niel, Christian; Villela-Nogueira, Cristiane A.; Pannain, Vera; Araujo, Natalia M.

    2016-01-01

    Hepatocellular carcinoma (HCC) is the second most common cause of cancer mortality worldwide. Most cases of HCC are associated with cirrhosis related to chronic hepatitis B virus or hepatitis C virus infections. Hypermethylation of promoter regions is the main epigenetic mechanism of gene silencing and has been involved in HCC development. The aim of this study was to determine whether aberrant methylation of RASSF1A and DOK1 gene promoters is associated with the progression of liver disease in Brazilian patients. Methylation levels were measured by pyrosequencing in 41 (20 HCC, 9 cirrhotic, and 12 non-cirrhotic) liver tissue samples. Mean rates of methylation in RASSF1A and DOK1 were 16.2% and 12.0% in non-cirrhotic, 26.1% and 19.6% in cirrhotic, and 59.1% and 56.0% in HCC tissues, respectively, showing a gradual increase according to the progression of the disease, with significantly higher levels in tumor tissues. In addition, hypermethylation of RASSF1A and DOK1 was found in the vast majority (88%) of the HCC cases. Interestingly, DOK1 methylation levels in HCC samples were significantly higher in the group of younger (<40 years) patients, and higher in moderately differentiated than in poorly differentiated tumors (p < 0.05). Our results reinforce the hypothesis that hypermethylation of RASSF1A and DOK1 contributes to hepatocarcinogenesis and is associated to clinicopathological characteristics. RASSF1A and DOK1 promoter hypermethylation may be a valuable biomarker for early diagnosis of HCC and a potential molecular target for epigenetic-based therapy. PMID:27078152

  14. Cardiovascular complications of non-insulin-dependent diabetes: the JCR:LA-cp rat.

    Science.gov (United States)

    Clark, T A; Pierce, G N

    2000-01-01

    Diabetes is a serious medical and financial burden on western societies. It is the seventh leading cause of death in the United States and Canada. The disease is due to a primary defect in glucose tolerance and carbohydrate metabolism resulting from either a deficiency of insulin (Insulin-dependent (type I) diabetes mellitus - IDDM) or a state of insulin resistance (Non-insulin-dependent (type II) diabetes mellitus - NIDDM). NIDDM comprises greater than 80% of total diabetic cases. Associated with the primary metabolic defects are equally deleterious secondary complications affecting the renal, ocular, nervous and cardiovascular systems. The cardiovascular complications account for a major proportion of diabetic mortality. As such, it is of paramount importance to develop or find an animal model expressing complications homologous to the human condition. Many models of NIDDM are available to the diabetic researcher but choosing an accurate one can be difficult. The following compares the advantages and limitations of one such model, the JCR:LA-cp rat to other NIDDM models commonly used today.

  15. Fatigue resistance of rat extraocular muscles does not depend on creatine kinase activity

    Directory of Open Access Journals (Sweden)

    Hayeß Katrin

    2005-08-01

    Full Text Available Abstract Background Creatine kinase (CK links phosphocreatine, an energy storage system, to cellular ATPases. CK activity serves as a temporal and spatial buffer for ATP content, particularly in fast-twitch skeletal muscles. The extraocular muscles are notoriously fast and active, suggesting the need for efficient ATP buffering. This study tested the hypotheses that (1 CK isoform expression and activity in rat extraocular muscles would be higher, and (2 the resistance of these muscles to fatigue would depend on CK activity. Results We found that mRNA and protein levels for cytosolic and mitochondrial CK isoforms were lower in the extraocular muscles than in extensor digitorum longus (EDL. Total CK activity was correspondingly decreased in the extraocular muscles. Moreover, cytoskeletal components of the sarcomeric M line, where a fraction of CK activity is found, were downregulated in the extraocular muscles as was shown by immunocytochemistry and western blotting. CK inhibition significantly accelerated the development of fatigue in EDL muscle bundles, but had no major effect on the extraocular muscles. Searching for alternative ATP buffers that could compensate for the relative lack of CK in extraocular muscles, we determined that mRNAs for two adenylate kinase (AK isoforms were expressed at higher levels in these muscles. Total AK activity was similar in EDL and extraocular muscles. Conclusion These data indicate that the characteristic fatigue resistance of the extraocular muscles does not depend on CK activity.

  16. Early maternal deprivation in rats induces gender-dependent effects on developing hippocampal and cerebellar cells.

    Science.gov (United States)

    Llorente, Ricardo; Gallardo, Meritxell López; Berzal, Alvaro Llorente; Prada, Carmen; Garcia-Segura, Luis Miguel; Viveros, María-Paz

    2009-05-01

    Adult animals submitted to a single prolonged episode of maternal deprivation [24h, postnatal day 9-10] show behavioral alterations that resemble specific symptoms of schizophrenia. According to the neurodevelopmental theory, these behavioral deficits might be mediated by detrimental neurodevelopmental processes that might be associated, at least partially, with stress-induced corticosterone responses. In order to address this hypothesis, we have focused on the hippocampus and cerebellar cortex, two brain regions that show high density of glucocorticoid receptors, and analyzed possible neuronal and glial alterations by immunohistochemical techniques. To evaluate the presence of degenerated neurons we used Fluoro-Jade-C (FJ-C) staining and for the study of astrocytes we employed glial fibrillary acidic protein (GFAP). Within control animals, females showed significantly more GFAP positive cells than males and a trend towards more FJ-C positive cells. Maternal deprivation induced neuronal degeneration and astroglial changes in the hippocampus and cerebellar cortex of neonatal rats that, in general, were more marked in males. This differential effect may be attributable to a greater vulnerability of males to this kind of early environmental insult and/or to sex-dependent differences in the onset and/or progression of the effects. The present experimental procedure may be instrumental in elucidating sex-dependent mechanisms of neurodevelopmental psychiatric disorders with a basis in early environmental insults.

  17. Temperature dependence and GABA modulation of (TH)triazolam binding in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Earle, M.E.; Concas, A.; Wamsley, J.K.; Yamamura, H.I.

    1987-07-27

    The hypnotic triazolam (TZ), a triazolobenzodiazepine displays a short physiological half life and has been used for the treatment of insomnia related to anxiety states. The authors major objectives were the direct measurement of the temperature dependence and the gamma-aminobutyric acid (GABA) effect of (TH)TZ binding in the rat brain. Saturation studies showed a shift to lower affinity with increasing temperatures (K/sub d/ = 0.27 +/- 08 nM at 0C; K/sub d/ = 1.96 +/- 0.85 nM at 37C) while the B/sub max/ values remained unchanged (1220 +/- 176 fmoles/mg protein at 0C and 1160 +/- 383 fmoles/mg protein at 37C). Saturation studies of (TH)TZ binding in the presence or absence of GABA (100 M) showed a GABA-shift. At 0C the K/sub d/ values were (K/sub d/ = 0.24 +/- 0.03 nM/-GABA; K/sub d/ = 0.16 +/- 0.04/+GABA) and at 37C the K/sub d/ values were (K/sub d/ = 1.84 +/- 0.44 nM/-GABA; K/sub d/ = 0.95 +/- 0.29 nM/+GABA). In contrast to reported literature, the authors findings show that TZ interacts with benzodiazepine receptors with a temperature dependence and GABA-shift consistent with predicted behavior for benzodiazepine agonists. 20 references, 3 tables.

  18. Temperature dependence and GABA modulation of [3H]triazolam binding in the rat brain

    International Nuclear Information System (INIS)

    The hypnotic triazolam (TZ), a triazolobenzodiazepine displays a short physiological half life and has been used for the treatment of insomnia related to anxiety states. The authors major objectives were the direct measurement of the temperature dependence and the gamma-aminobutyric acid (GABA) effect of [3H]TZ binding in the rat brain. Saturation studies showed a shift to lower affinity with increasing temperatures (K/sub d/ = 0.27 +/- 08 nM at 00C; K/sub d/ = 1.96 +/- 0.85 nM at 370C) while the B/sub max/ values remained unchanged (1220 +/- 176 fmoles/mg protein at 00C and 1160 +/- 383 fmoles/mg protein at 370C). Saturation studies of [3H]TZ binding in the presence or absence of GABA (100μM) showed a GABA-shift. At 00C the K/sub d/ values were (K/sub d/ = 0.24 +/- 0.03 nM/-GABA; K/sub d/ = 0.16 +/- 0.04/+GABA) and at 370C the K/sub d/ values were (K/sub d/ = 1.84 +/- 0.44 nM/-GABA; K/sub d/ = 0.95 +/- 0.29 nM/+GABA). In contrast to reported literature, the authors findings show that TZ interacts with benzodiazepine receptors with a temperature dependence and GABA-shift consistent with predicted behavior for benzodiazepine agonists. 20 references, 3 tables

  19. Impaired endothelium-dependent and -independent relaxation of aorta from diabetic rats.

    Science.gov (United States)

    Yakubu, M A; Sofola, O A; Igbo, I; Oyekan, A O

    2012-01-01

    Vascular complication in diabetes has been reported to be due to the effects of chronic high blood glucose on the vascular system. Different relaxation mechanisms exist in the vasculature and effect of chronic high glucose on vascular relaxation mechanisms is not clearly understood. We assessed the effect of streptozotocin (STZ, 70 mg/kg, for 12 wks)-induced diabetes on vascular reactivity to isoproterenol (Isop, 10-9-10-5 M), a cAMP-dependent agent, acetylcholine (ACh, 10-9-10-5 M), a stimulant of NO (nitric oxide) synthase, sodium nitroprusside (SNP, 10-10-10-5 M), NO donor, or bradykinin (BK, 10-9-10-5 M) in the rat isolated aortic ring. Isop, ACh, SNP, or BK dose-dependently relaxed phenylephrine (PE, 10-7 M) pre-constricted ring producing a maximum relaxation of 82 % for Isop (10-5 M), 85 % for ACh (10-5 M), 100 % for SNP (10-6 M), and 30 % for BK (10-5 M) respectively. STZ attenuated Isop, ACh, and BK-induced relaxation by 45 % (n=7, pn (Fig. 5, Ref. 24). PMID:22394031

  20. Boldine enhances bile production in rats via osmotic and Farnesoid X receptor dependent mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Cermanova, Jolana [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Kadova, Zuzana [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Deparment of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove (Czech Republic); Zagorova, Marie [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Hroch, Milos [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Department of Medical Biochemistry, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Tomsik, Pavel [Department of Medical Biochemistry, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Nachtigal, Petr; Kudlackova, Zdenka [Department of Biological and Medical Sciences, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove (Czech Republic); Pavek, Petr; Dubecka, Michaela; Ceckova, Martina; Staud, Frantisek [Deparment of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove (Czech Republic); Laho, Tomas [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Micuda, Stanislav, E-mail: micuda@lfhk.cuni.cz [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic)

    2015-05-15

    Boldine, the major alkaloid from the Chilean Boldo tree, is used in traditional medicine to support bile production, but evidence to support this function is controversial. We analyzed the choleretic potential of boldine, including its molecular background. The acute- and long-term effects of boldine were evaluated in rats either during intravenous infusion or after 28-day oral treatment. Infusion of boldine instantly increased the bile flow 1.4-fold in healthy rats as well as in animals with Mrp2 deficiency or ethinylestradiol induced cholestasis. This effect was not associated with a corresponding increase in bile acid or glutathione biliary excretion, indicating that the effect is not related to stimulation of either bile acid dependent or independent mechanisms of bile formation and points to the osmotic activity of boldine itself. We subsequently analyzed bile production under conditions of changing biliary excretion of boldine after bolus intravenous administration and found strong correlations between both parameters. HPLC analysis showed that bile concentrations of boldine above 10 μM were required for induction of choleresis. Importantly, long-term pretreatment, when the bile collection study was performed 24-h after the last administration of boldine, also accelerated bile formation despite undetectable levels of the compound in bile. The effect paralleled upregulation of the Bsep transporter and increased biliary clearance of its substrates, bile acids. We consequently confirmed the ability of boldine to stimulate the Bsep transcriptional regulator, FXR receptor. In conclusion, our study clarified the mechanisms and circumstances surrounding the choleretic activity of boldine. - Highlights: • Boldine may increase bile production by direct as well as indirect mechanisms. • Biliary concentrations of boldine above 10 μM directly stimulate bile production. • Long-term oral boldine administration increases bile acid (BA) biliary secretion. • Boldine

  1. Death mode-dependent reduction in succinate dehydrogenase activity in hair cells of aging rat cochleae

    Institute of Scientific and Technical Information of China (English)

    YANG Wei-ping; HU Bo-hua; SUN Jian-he; ZHAI Suo-qiang; Donald Henderson

    2010-01-01

    Background Our previous studies have shown that both apoptosis and necrosis are involved in hair cell (HC) pathogenesis in aging cochleae. To better understand the biological mechanisms responsible for the regulation of HC death, we examined the activity of succinate dehydrogenase (SDH), a mitochondrial bioenergetic enzyme, in the HCs of aging cochleae.Methods The auditory brainstem response thresholds elicited by tone bursts at 4, 10 and 20 kHz were measured in both young (2-3 months) and aging (22-23 months) Wistar rats. SDH activity was evaluated with a colorimetric assay using nitroblue tetrazolium monosodium salt. The SDH-labeled organs of Corti were double stained with propidium iodide, a DNA intercalating fluorescent probe for illustration of HC nuclei. All the specimens were examined with fluorescence microscopy and confocal microscopy.Results Aging rats exhibited a significant elevation of ABR thresholds with threshold shifts being 34 dB at 20 kHz, 28 dB at 10 kHz, and 25 dB at 4 kHz. Consistent with the reduction in the cochlear function, aging cochleae exhibited the reduction of SDH staining intensity in the apical and the basal ends of the cochleae, where a large number of apoptotic, necrotic, and missing HCs were evident. The reduction in SDH staining appeared in a cell-death-mode dependent fashion. Specifically, SDH labeling remained in apoptotic HCs. In contrast, SDH staining was markedly reduced or absent in necrotic HCs.Conclusions In the aging cochlea, SDH activity is preserved in HCs undergoing apoptosis, but is substantially reduced in necrosis. These results suggest that mitochondrial energetic function is involved in the regulation of cell death pathways in the pathogenesis of aging cochleae.

  2. Boldine enhances bile production in rats via osmotic and Farnesoid X receptor dependent mechanisms

    International Nuclear Information System (INIS)

    Boldine, the major alkaloid from the Chilean Boldo tree, is used in traditional medicine to support bile production, but evidence to support this function is controversial. We analyzed the choleretic potential of boldine, including its molecular background. The acute- and long-term effects of boldine were evaluated in rats either during intravenous infusion or after 28-day oral treatment. Infusion of boldine instantly increased the bile flow 1.4-fold in healthy rats as well as in animals with Mrp2 deficiency or ethinylestradiol induced cholestasis. This effect was not associated with a corresponding increase in bile acid or glutathione biliary excretion, indicating that the effect is not related to stimulation of either bile acid dependent or independent mechanisms of bile formation and points to the osmotic activity of boldine itself. We subsequently analyzed bile production under conditions of changing biliary excretion of boldine after bolus intravenous administration and found strong correlations between both parameters. HPLC analysis showed that bile concentrations of boldine above 10 μM were required for induction of choleresis. Importantly, long-term pretreatment, when the bile collection study was performed 24-h after the last administration of boldine, also accelerated bile formation despite undetectable levels of the compound in bile. The effect paralleled upregulation of the Bsep transporter and increased biliary clearance of its substrates, bile acids. We consequently confirmed the ability of boldine to stimulate the Bsep transcriptional regulator, FXR receptor. In conclusion, our study clarified the mechanisms and circumstances surrounding the choleretic activity of boldine. - Highlights: • Boldine may increase bile production by direct as well as indirect mechanisms. • Biliary concentrations of boldine above 10 μM directly stimulate bile production. • Long-term oral boldine administration increases bile acid (BA) biliary secretion. • Boldine

  3. Papaverine-induced and endothelium-dependent relaxation in the isolated rat aortic strip.

    Directory of Open Access Journals (Sweden)

    Seçilmis A

    1999-08-01

    Full Text Available In the present study, we aimed to obtain further evidence in favour of the hypothesis that nitric oxide (NO is a major mediator of endothelium-dependent vasorelaxation and to clarify whether NO plays a role in papaverine-induced vasorelaxation. The relaxant effects of acetylcholine (Ach, acidified NaNO2 or papaverine were investigated on isolated helical strips of the rat thoracic aorta precontracted with phenylephrine in an organ bath containing Krebs solution aerated with 95% O2 and 5% CO2. The relaxation was quantified as % peak reduction of phenylephrine contracture. Saponin abolished the relaxant effects of Ach completely whereas it had no effect on the responses to acidified NaNO2 or papaverine. NG-nitro-L-arginine (L-NOARG reduced the effects of Ach significantly, but it was ineffective on the relaxation induced by acidified NaNO2. The inhibitory action of L-NOARG was partly restored by L-arginine, but not by D-arginine. Hemoglobin, hydroxocobalamin and hydroquinone exhibited significant inhibition on the relaxation evoked by Ach and acidified NaNO2. L-NOARG, hydroxocobalamin and hydroquinone caused only limited but significant decrease in the relaxation due to papaverine. This phenomenon was also observed by increasing phenylephrine concentration leading to an enhancement in the contraction. Our findings strongly support the view that Ach-induced relaxation of rat aorta strips is mediated by free NO released from the endothelium and the results suggest that NO may indirectly contribute to papaverine-induced relaxation.

  4. Aging-dependent changes in rat heart mitochondrial glutaredoxins—Implications for redox regulation

    Directory of Open Access Journals (Sweden)

    Xing-Huang Gao

    2013-01-01

    Full Text Available Clinical and animal studies have documented that hearts of the elderly are more susceptible to ischemia/reperfusion damage compared to young adults. Recently we found that aging-dependent increase in susceptibility of cardiomyocytes to apoptosis was attributable to decrease in cytosolic glutaredoxin 1 (Grx1 and concomitant decrease in NF-κB-mediated expression of anti-apoptotic proteins. Besides primary localization in the cytosol, Grx1 also exists in the mitochondrial intermembrane space (IMS. In contrast, Grx2 is confined to the mitochondrial matrix. Here we report that Grx1 is decreased by 50–60% in the IMS, but Grx2 is increased by 1.4–2.6 fold in the matrix of heart mitochondria from elderly rats. Determination of in situ activities of the Grx isozymes from both subsarcolemmal (SSM and interfibrillar (IFM mitochondria revealed that Grx1 was fully active in the IMS. However, Grx2 was mostly in an inactive form in the matrix, consistent with reversible sequestration of the active-site cysteines of two Grx2 molecules in complex with an iron–sulfur cluster. Our quantitative evaluations of the active/inactive ratio for Grx2 suggest that levels of dimeric Grx2 complex with iron–sulfur clusters are increased in SSM and IFM in the hearts of elderly rats. We found that the inactive Grx2 can be fully reactivated by sodium dithionite or exogenous superoxide production mediated by xanthine oxidase. However, treatment with rotenone, which generates intramitochondrial superoxide through inhibition of mitochondrial respiratory chain Complex I, did not lead to Grx2 activation. These findings suggest that insufficient ROS accumulates in the vicinity of dimeric Grx2 to activate it in situ.

  5. Boldine enhances bile production in rats via osmotic and farnesoid X receptor dependent mechanisms.

    Science.gov (United States)

    Cermanova, Jolana; Kadova, Zuzana; Zagorova, Marie; Hroch, Milos; Tomsik, Pavel; Nachtigal, Petr; Kudlackova, Zdenka; Pavek, Petr; Dubecka, Michaela; Ceckova, Martina; Staud, Frantisek; Laho, Tomas; Micuda, Stanislav

    2015-05-15

    Boldine, the major alkaloid from the Chilean Boldo tree, is used in traditional medicine to support bile production, but evidence to support this function is controversial. We analyzed the choleretic potential of boldine, including its molecular background. The acute- and long-term effects of boldine were evaluated in rats either during intravenous infusion or after 28-day oral treatment. Infusion of boldine instantly increased the bile flow 1.4-fold in healthy rats as well as in animals with Mrp2 deficiency or ethinylestradiol induced cholestasis. This effect was not associated with a corresponding increase in bile acid or glutathione biliary excretion, indicating that the effect is not related to stimulation of either bile acid dependent or independent mechanisms of bile formation and points to the osmotic activity of boldine itself. We subsequently analyzed bile production under conditions of changing biliary excretion of boldine after bolus intravenous administration and found strong correlations between both parameters. HPLC analysis showed that bile concentrations of boldine above 10 μM were required for induction of choleresis. Importantly, long-term pretreatment, when the bile collection study was performed 24-h after the last administration of boldine, also accelerated bile formation despite undetectable levels of the compound in bile. The effect paralleled upregulation of the Bsep transporter and increased biliary clearance of its substrates, bile acids. We consequently confirmed the ability of boldine to stimulate the Bsep transcriptional regulator, FXR receptor. In conclusion, our study clarified the mechanisms and circumstances surrounding the choleretic activity of boldine. PMID:25771127

  6. Endothelium-dependent Effect of Sesame Seed Feeding on Vascular Reactivity of Streptozotocin-diabetic Rats: Underlying Mechanisms.

    Science.gov (United States)

    Roghani, Mehrdad; Jalali-Nadoushan, Mohammad Reza; Baluchnejadmojarad, Tourandokht; Vaez Mahdavi, Mohammad-Reza; Naderi, Gholamali; Roghani Dehkordi, Farshad; Joghataei, Mohammad Taghi

    2013-01-01

    Cardiovascular disorders continue to constitute major causes of morbidity and mortality in diabetic patients. In this study, the effect of chronic administration of sesame (Sesamum indicum L) seed feeding was studied on aortic reactivity of streptozotocin (STZ)-diabetic rats. Male diabetic rats received sesame seed-mixed food at weight ratios of 3% and 6% for 7 weeks, one week after diabetes induction. Contractile responses to KCl and phenylephrine (PE) and relaxation response to acetylcholine (ACh) and sodium nitroprusside (SNP) were obtained from aortic rings. Maximum contractile response of endothelium-intact rings to PE was significantly lower in sesame-treated diabetic rats (at a ratio of 6%) relative to untreated diabetics and endothelium removal abolished this difference. Endothelium-dependent relaxation to ACh was also significantly higher in sesame-treated diabetic rats (at a ratio of 6%) as compared to diabetic rats and pretreatment of rings with nitric oxide synthase inhibitor, N(G)-nitro-l-arginine methyl ester (L-NAME) significantly attenuated the observed response. Two-month diabetes also resulted in an elevation of malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activity and sesame treatment significantly reversed the increased MDA content and restored activity of SOD. We thus conclude that chronic treatment of diabetic rats with sesame seed could in a dose-manner prevent some abnormal changes in vascular reactivity through nitric oxide and via attenuation of oxidative stress in aortic tissue and endothelium integrity is necessary for this beneficial effect.

  7. High-fat feeding reduces endothelium-dependent vasodilation in rats: differential mechanisms for saturated and unsaturated fatty acids?

    Science.gov (United States)

    Song, Guang-Yao; Gao, Yu; Di, Yu-Wei; Pan, Li-Li; Zhou, Yu; Ye, Ji-Ming

    2006-08-01

    1. Chronic feeding with a high-fat diet can cause metabolic syndrome in rodents similar to humans, but the role of saturated versus unsaturated fats in vascular tension remains unclear. 2. The present study shows that rats on a diet rich in either saturated or unsaturated fat had higher blood pressure compared with chow-fed rats (approximately 130 vs 100 mmHg, respectively), along with hyperlipidaemia and insulin resistance. Compared with responses of phenylephrine-preconstricted artery segments from chow-fed rats, vasorelaxation of isolated renal arteries from high-fat fed rats was reduced substantially (> 50%) in response to acetylcholine (0.01-10 micromol/L) and moderately to nitroprusside (>or=1 micromol/L) at low concentrations. Acetylcholine-induced vasorelaxation of arteries from high-fat fed rats was also more sensitive to inhibition by the nitric oxide (NO) synthase inhibitors NG-nitro-L-arginine and methylene blue. 3. In human umbilical vein endothelial cells, the production of NO and endothelin-1 was significantly inhibited by unsaturated fatty acids. In comparison, saturated fatty acids stimulated endothelin-1 production without altering NO production. 4. The data indicate that both saturated and unsaturated high-fat feeding may result in an increase in blood pressure owing to reduced endothelium-dependent vasorelaxation in the arterial system. The impaired endothelium-dependent vasorelaxation induced by saturated and unsaturated fatty acids may involve different mechanisms.

  8. Role of acid sphingomyelinase in the age-dependent dysregulation of sphingolipids turnover in the tissues of rats.

    Science.gov (United States)

    Babenko, Nataliya A; Garkavenko, Vladimir V; Storozhenko, Galina V; Timofiychuk, Olga A

    2016-04-01

    Old age-associated pathologies usually coincide with altered sphingolipid metabolism. In the present article, the role of acid sphingomyelinase (ASMase) in the age-dependent changes of sphingomyelin (SM) and ceramide contents in the tissues has been investigated by means of ASMase inhibitors, imipramine and zoledronic acid. It has been determined that ceramide content and ceramide/SM ratio increased, while SM level decreased in the heart, liver, blood serum and skeletal muscles of 24-month old rats in contrast to 3-month old animals. Injections of imipramine or zoledronic acid to 24-month old rats resulted in significant downregulation of ASMase in the liver and skeletal and heart muscles. The both inhibitors decreased the ceramide content and ceramide/SM ratio and increased the SM content in all tissues studied, except the heart, of old rats to the levels close to those observed in the young animals. Long-term treatment of rats by inhibitors, which have different mechanisms of action on ASMase, exerts the similar, but not equal effects on enzyme activity and SM turnover. In summary, the data above strongly suggest that the age-dependent up-regulation of ASMase plays an important role in the modulation of ceramide and SM contents in rat tissues and that imipramine and zoledronic acid are useful tools for SM turnover manipulation at old age. PMID:26830134

  9. Somatostatin receptors in the nucleus accumbens modulate dopamine-dependent but not acetylcholine-dependent turning behaviour of rats.

    NARCIS (Netherlands)

    Ikeda, H.; Kotani, A.; Koshikawa, N.; Cools, A.R.

    2009-01-01

    The role of somatostatin receptors in the nucleus accumbens shell in rat turning behaviour was studied. Unilateral injection of neither the somatostatin receptor agonist somatostatin (1.0 microg) nor the somatostatin receptor antagonist cyclosomatostatin (100.0 ng) into the nucleus accumbens shell e

  10. Evidence for time-of-day dependent effect of neurotoxic dorsomedial hypothalamic lesions on food anticipatory circadian rhythms in rats.

    Directory of Open Access Journals (Sweden)

    Glenn J Landry

    Full Text Available The dorsomedial hypothalamus (DMH is a site of circadian clock gene and immediate early gene expression inducible by daytime restricted feeding schedules that entrain food anticipatory circadian rhythms in rats and mice. The role of the DMH in the expression of anticipatory rhythms has been evaluated using different lesion methods. Partial lesions created with the neurotoxin ibotenic acid (IBO have been reported to attenuate food anticipatory rhythms, while complete lesions made with radiofrequency current leave anticipatory rhythms largely intact. We tested a hypothesis that the DMH and fibers of passage spared by IBO lesions play a time-of-day dependent role in the expression of food anticipatory rhythms. Rats received intra-DMH microinjections of IBO and activity and body temperature (T(b rhythms were recorded by telemetry during ad-lib food access, total food deprivation and scheduled feeding, with food provided for 4-h/day for 20 days in the middle of the light period and then for 20 days late in the dark period. During ad-lib food access, rats with DMH lesions exhibited a lower amplitude and mean level of light-dark entrained activity and T(b rhythms. During the daytime feeding schedule, all rats exhibited food anticipatory activity and T(b rhythms that persisted during 2 days without food in constant dark. In some rats with partial or total DMH ablation, the magnitude of the anticipatory rhythm was weak relative to most intact rats. When mealtime was shifted to the late night, the magnitude of the food anticipatory activity rhythms in these cases was restored to levels characteristic of intact rats. These results confirm that rats can anticipate scheduled daytime or nighttime meals without the DMH. Improved anticipation at night suggests a modulatory role for the DMH in the expression of food anticipatory activity rhythms during the daily light period, when nocturnal rodents normally sleep.

  11. Transient voltage-dependent potassium currents are reduced in NTS neurons isolated from renal wrap hypertensive rats.

    Science.gov (United States)

    Belugin, Sergei; Mifflin, Steve

    2005-12-01

    Whole cell patch-clamp measurements were made in neurons enzymatically dispersed from the nucleus of the solitary tract (NTS) to determine if alterations occur in voltage-dependent potassium channels from rats made hypertensive (HT) by unilateral nephrectomy/renal wrap for 4 wk. Some rats had the fluorescent tracer DiA applied to the aortic nerve before the experiment to identify NTS neurons receiving monosynaptic baroreceptor afferent inputs. Mean arterial pressure (MAP) was greater in 4-wk HT (165 +/- 5 mmHg, n = 26, P NTS neurons from NT and HT rats. At activation voltages from -10 to +10 mV, TOCs were significantly less in HT neurons compared with those observed in NT neurons (P NTS neurons from NT and HT rats and was not different comparing neurons from NT and HT rats. However, examination of the subset of NTS neurons exhibiting somatic DiA fluorescence revealed that DiA-labeled neurons from HT rats had a significantly shorter duration delayed excitation (n = 8 cells, P = 0.022) than DiA-labeled neurons from NT rats (n = 7 cells). Neurons with delayed excitation from HT rats had a significantly broader first action potential (AP) and a slower maximal downstroke velocity of repolarization compared with NT neurons with delayed excitation (P = 0.016 and P = 0.014, respectively). The number of APs in the first 200 ms of a sustained depolarization was greater in HT than NT neurons (P = 0.012). These results suggest that HT of 4-wk duration reduces TOCs in NTS neurons, and this contributes to reduced delayed excitation and increased AP responses to depolarizing inputs. Such changes could alter baroreflex function in hypertension.

  12. Serum levels of soluble Fas, nitric oxide and cytokines in acute decompensated cirrhotic patients

    Institute of Scientific and Technical Information of China (English)

    Christoph Elsing; Sabine Harenberg; Wolfgang Stremmel; Thomas Herrmann

    2007-01-01

    AIM: To evaluate plasma levels of nitrite/nitrate (NOx),soluble Fas (sFas) antigen, tumor necrosis factor alpha(TNF-α) and interleukin-6 (TL-6) in patients with compensated and acute decompensated cirrhosis and to evaluate mediators causing acute decompensation in liver cirrhosis.METHODS: This prospective study was conducted in the medical intensive care unit of an academic tertiary center. Fifty-five patients with acute decompensation (gastrointestinal hemorrhage, encephalopathy, hydropic decompensation) and twenty-five patients with compensated liver cirrhosis were included. Blood samples were taken for analyses of sfas, Nox, TL-6, TNF-α. Liver enzymes and kidney functions were also tested.RESULTS: In patients with acute decompensation, plasma sfas levels were higher than in non-decompensated patients (15305±4646 vs 12458 ± 4322 pg/mL, P <0.05). This was also true for the subgroup of patients with alcoholic liver cirrhosis (P < 0.05). The other mediators were not different and none of the parameters predicted survival, except for ALT (alanine-aminotransferase). In patients with portal-hypertension-induced acute hemorrhage, NOx levels were significantly lower than in patients with other forms of decompensation (70.8 ±48.3 vs 112.9 ± 74.9 pg/mL, P < 0.05). When NOx levels were normalized to creatinine levels, the difference disappeared. IL-6, TNF-α and sfas were not different between bleeders and non-bleeders. In decompensated patients sfas, IL-6 and NOx levels correlated positively with creatinine levels, while IL-6 levels were dependent on Child class.CONCLUSION: In acute decompensated cirrhotic patients sFas is increased, suggesting a role of apoptosis in this process and patients with acute bleeding have lower NOx levels. However, in this acute complex clinical situation, kidney function seems to have a predominant influence on mediator levels.

  13. Cirrhotic cardiomyopathy: a pathophysiological review of circulatory dysfunction in liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik Sahl

    2002-01-01

    The systemic circulation in patients with cirrhosis is hyperdynamic with an increased cardiac output and heart rate and a reduced systemic vascular resistance as the most pronounced alterations. The concomitant cardiac dysfunction has recently been termed "cirrhotic cardiomyopathy", which is an...... stress the heart such as shunt implantation and liver transplantation....

  14. Cirrhotic cardiomyopathy: a pathophysiological review of circulatory dysfunction in liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik

    2002-01-01

    The systemic circulation in patients with cirrhosis is hyperdynamic with an increased cardiac output and heart rate and a reduced systemic vascular resistance as the most pronounced alterations. The concomitant cardiac dysfunction has recently been termed "cirrhotic cardiomyopathy", which is an...

  15. Cirrhotic cardiomyopathy: a pathophysiological review of circulatory dysfunction in liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik

    2002-01-01

    The systemic circulation in patients with cirrhosis is hyperdynamic with an increased cardiac output and heart rate and a reduced systemic vascular resistance as the most pronounced alterations. The concomitant cardiac dysfunction has recently been termed "cirrhotic cardiomyopathy", which is an e...... stress the heart such as shunt implantation and liver transplantation....

  16. Inhibitors of glutamate dehydrogenase block sodium-dependent glutamate uptake in rat brain membranes

    Directory of Open Access Journals (Sweden)

    Brendan S Whitelaw

    2013-09-01

    Full Text Available We recently found evidence for anatomic and physical linkages between the astroglial Na+-dependent glutamate transporters (GLT-1/EAAT2 and GLAST/EAAT1 and mitochondria. In these same studies, we found that the glutamate dehydrogenase (GDH inhibitor, epigallocatechin-monogallate (EGCG, inhibits both glutamate oxidation and Na+-dependent glutamate uptake in astrocytes. In the present study, we extend this finding by exploring the effects of EGCG on Na+-dependent L-[3H]-glutamate (Glu uptake in crude membranes (P2 prepared from rat brain cortex. In this preparation, uptake is almost exclusively mediated by GLT-1. EGCG inhibited L-[3H]-Glu uptake in cortical membranes with an IC50 value of 230 µM. We also studied the effects of two additional inhibitors of GDH, hexachlorophene (HCP and bithionol (BTH. Both of these compounds also caused concentration-dependent inhibition of glutamate uptake in cortical membranes. Pre-incubating with HCP for up to 15 min had no greater effect than that observed with no pre-incubation, showing that the effects occur rapidly. HCP decreased the Vmax for glutamate uptake without changing the Km, consistent with a non-competitive mechanism of action. EGCG, HCP, and BTH also inhibited Na+-dependent transport of D-[3H]-aspartate (Asp, a non-metabolizable substrate, and [3H]-γ-aminobutyric acid (GABA. In contrast to the forebrain, glutamate uptake in crude cerebellar membranes (P2 is likely mediated by GLAST (EAAT1. Therefore, the effects of these compounds were examined in cerebellar membranes. In this region, none of these compounds had any effect on uptake of either L-[3H]-Glu or D-[3H]-Asp, but they all inhibited [3H]-GABA uptake. Together these studies suggest that GDH is preferentially required for glutamate uptake in forebrain as compared to cerebellum, and GDH may be required for GABA uptake as well. They also provide further evidence for a functional linkage between glutamate transport and mitochondria.

  17. HGF, MET, and matrix-related proteases in hepatocellular carcinoma, fibrolamellar variant, cirrhotic and normal liver.

    Science.gov (United States)

    Schoedel, Karen E; Tyner, Valerie Zajac; Kim, Tae-Hyoung; Michalopoulos, George K; Mars, Wendy M

    2003-01-01

    Fibrolamellar variant is an uncommon subcategory of hepatocellular carcinoma with a better prognostic outcome. Proteinases and growth factors that are involved in the remodeling of extracellular matrix may influence the behavior of cancers. To determine whether these factors contribute to the distinct etiologies of fibrolamellar hepatocellular carcinoma and traditional hepatocellular carcinoma, we assayed hepatocyte growth factor, the hepatocyte growth factor receptor, and two hepatocyte growth factor activators, hepatocyte growth factor activator and urokinase-type plasminogen activator, in hepatocellular carcinoma, fibrolamellar hepatocellular carcinoma, cirrhotic liver and normal liver. In addition, we examined the urokinase-type plasminogen activator receptor, the type 1 plasminogen activator inhibitor, plasmin, fibrinogen, and the type IV matrix metalloproteinases. Eighteen hepatocellular carcinomas and 11 fibrolamellar hepatocellular carcinomas were obtained as paraffin embedded sections from the University of Pittsburgh Department of Pathology. Frozen tissues from a subset of cases (9 hepatocellular carcinomas, 4 fibrolamellar hepatocellular carcinomas, 12 cirrhotic livers and 2 normal livers) were also available for analysis. Antibodies against urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor, hepatocyte growth factor and hepatocyte growth factor receptor were used to analyze immunoperoxidase stained slides from the paraffin blocks. Western blot analyses using antibodies against hepatocyte growth factor, hepatocyte growth factor receptor, phosphotyrosine, hepatocyte growth factor activator, urokinase-type plasminogen activator receptor, urokinase-type plasminogen activator, plasminogen activator inhibitor-1, fibrinogen and plasmin were performed on membrane-enriched fractions from the frozen tissue, as was collagen zymography for matrix metalloproteinase-2 and matrix metalloproteinase-9. The most notable findings are as

  18. Mg2+-dependent ATPase activity in cardiac myofibrils from the insulin-resistant JCR:LA-cp rat.

    Science.gov (United States)

    Misra, T; Russell, J C; Clark, T A; Pierce, G N

    2001-01-01

    There is a great deal of information presently available documenting a cardiomyopathic condition in insulin-deficient models of diabetes. Less information is available documenting a similar status in non insulin-dependent models of diabetes. We have studied the functional integrity of the myofibrils isolated from hearts of JCR:LA rats. The JCR:LA rat is hyperinsulinemic, hyperlipidemic, glucose intolerant and obese. As such, it carries many of the characteristics found in humans with non insulin-dependent diabetes mellitus. These animals also have many indications of heart disease. However, it is not clear if the hearts suffer from vascular complications or are cardiomyopathic in nature. We examined Mg2+-dependent myofibrillar ATPase in hearts of JCR:LA-cp/cp rats and their corresponding control animals (+/?) and found no significant differences (P> 0.05). This is in striking contrast to the depression in this activity exhibited by cardiac myofibrils isolated from insulin-deficient models of diabetes. Our data demonstrate that myofibrillar functional integrity is normal in JCR:LA-cp rats and suggest that these hearts are not in a cardiomyopathic state. Insulin status may be critical in generating a cardiomyopathic condition in diabetes.

  19. An Age-Dependent Physiologically-Based Pharmacokinetic/Pharmacodynamic Model for the Organophosphorus Insecticide Chlorpyrifos in the Preweanling Rat

    Energy Technology Data Exchange (ETDEWEB)

    Timchalk, Chuck; Kousba, Ahmed A.; Poet, Torka S.

    2007-08-01

    Juvenile rats are more susceptible than adults to the acute toxicity of organophosphorus insecticides like chlorpyrifos (CPF). Age- and dose-dependent differences in metabolism may be responsible. Of importance is CYP450 activation and detoxification of CPF to chlorpyrifos-oxon (CPF-oxon) and trichloropyridinol (TCP), as well as B-esterase (cholinesterase; ChE) and A-esterase (PON-1) detoxification of CPF-oxon to TCP. In the current study, a modified physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model incorporating age-dependent changes in CYP450, PON-1, and tissue ChE levels for rats was developed. In this model, age was used as a dependent function to estimate body weight which was then used to allometrically scale both metabolism and tissue ChE levels. Model simulations suggest that preweanling rats are particularly sensitive to CPF toxicity, with levels of CPF-oxon in blood and brain disproportionately increasing, relative to the response in adult rats. This age-dependent non-linear increase in CPF-oxon concentration may potentially result from the depletion of non-target B-esterases, and a lower PON-1 metabolic capacity in younger animals. These results indicate that the PBPK/PD model behaves consistently with the general understanding of CPF toxicity, pharmacokinetics and tissue ChE inhibition in neonatal and adult rats. Hence, this model represents an important starting point for developing a computational model to assess the neurotoxic potential of environmentally relevant organophosphate exposures in infants and children.

  20. Histone demethylase retinoblastoma binding protein 2 regulates the expression of α-smooth muscle actin and vimentin in cirrhotic livers

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Q. [Department of Microbiology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Medicine, Shandong University, Jinan (China); Wang, L.X. [Department of Pharmacology, School of Medicine, Shandong University, Jinan (China); Zeng, J.P. [Department of Biochemistry, School of Medicine, Shandong University, Jinan (China); Liu, X.J.; Liang, X.M.; Zhou, Y.B. [Department of Microbiology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Medicine, Shandong University, Jinan (China)

    2013-09-06

    Liver cirrhosis is one of the most common diseases of Chinese patients. Herein, we report the high expression of a newly identified histone 3 lysine 4 demethylase, retinoblastoma binding protein 2 (RBP2), and its role in liver cirrhosis in humans. The siRNA knockdown of RBP2 expression in hepatic stellate cells (HSCs) reduced levels of α-smooth muscle actin (α-SMA) and vimentin and decreased the proliferation of HSCs; and overexpression of RBP2 increased α-SMA and vimentin levels. Treatment with transforming growth factor β (TGF-β) upregulated the expression of RBP2, α-SMA, and vimentin, and the siRNA knockdown of RBP2 expression attenuated TGF-β-mediated upregulation of α-SMA and vimentin expression and HSC proliferation. Furthermore, RBP2 was highly expressed in cirrhotic rat livers. Therefore, RBP2 may participate in the pathogenesis of liver cirrhosis by regulating the expression of α-SMA and vimentin. RBP2 may be a useful marker for the diagnosis and treatment of liver cirrhosis.

  1. Stoichiometry of H+ ejection during respiration-dependent accumulation of Ca2+ by rat liver mitochondria.

    Science.gov (United States)

    Brand, M D; Chen, C H; Lehninger, A L

    1976-02-25

    We have investigated the energy-dependent uptake of Ca2+ by rat liver mitochondria with succinate as respiratory substrate with rotenone added to block NAD-linked electron transport. In the presence of 3-hydroxybutyric or other permeant monocarboxylic acids Ca2+ was taken up to extents approaching those seen in the presence of phosphate. The quantitative relationship between cation and anion uptake was determined from the slope of a plot of 3-hydroxybutyrate uptake against Ca2+ uptake, a method which allowed determination of the stoichiometry without requiring ambiguous corrections for early nonenergized or nonstoichiometric binding events. This procedure showed that 2 molecules of 3-hydroxtbutyrate were accumulated with each Ca2+ ion. Under these conditions close to 2 Ca2+ ions and 4 molecules of 3-hydroxybutyrate were accumulated per pair of electrons per energy-conserving site of the respiratory chain. Since 3-hydroxybutyrate must be protonated to pass the membrane as the undissociated free acid, it is concluded that 4 protons were ejected (and subsequently reabsorbed) per pair of electrons per energy-conserving site, in contrast to the value 2.0 postulated by the chemiosmotic hypothesis.

  2. Stoichiometry of H+ ejection during respiration-dependent accumulation of Ca2+ by rat liver mitochondria.

    Science.gov (United States)

    Brand, M D; Chen, C H; Lehninger, A L

    1976-02-25

    We have investigated the energy-dependent uptake of Ca2+ by rat liver mitochondria with succinate as respiratory substrate with rotenone added to block NAD-linked electron transport. In the presence of 3-hydroxybutyric or other permeant monocarboxylic acids Ca2+ was taken up to extents approaching those seen in the presence of phosphate. The quantitative relationship between cation and anion uptake was determined from the slope of a plot of 3-hydroxybutyrate uptake against Ca2+ uptake, a method which allowed determination of the stoichiometry without requiring ambiguous corrections for early nonenergized or nonstoichiometric binding events. This procedure showed that 2 molecules of 3-hydroxtbutyrate were accumulated with each Ca2+ ion. Under these conditions close to 2 Ca2+ ions and 4 molecules of 3-hydroxybutyrate were accumulated per pair of electrons per energy-conserving site of the respiratory chain. Since 3-hydroxybutyrate must be protonated to pass the membrane as the undissociated free acid, it is concluded that 4 protons were ejected (and subsequently reabsorbed) per pair of electrons per energy-conserving site, in contrast to the value 2.0 postulated by the chemiosmotic hypothesis. PMID:2609

  3. Important role of energy-dependent mitochondrial pathways in cultured rat cardiac myocyte apoptosis.

    Science.gov (United States)

    Shiraishi, J; Tatsumi, T; Keira, N; Akashi, K; Mano, A; Yamanaka, S; Matoba, S; Asayama, J; Yaoi, T; Fushiki, S; Fliss, H; Nakagawa, M

    2001-10-01

    Recent studies have suggested that apoptosis and necrosis share common features in their signaling pathway and that apoptosis requires intracellular ATP for its mitochondrial/apoptotic protease-activating factor-1 suicide cascade. The present study was, therefore, designed to examine the role of intracellular energy levels in determining the form of cell death in cardiac myocytes. Neonatal rat cardiac myocytes were first incubated for 1 h in glucose-free medium containing oligomycin to achieve metabolic inhibition. The cells were then incubated for another 4 h in similar medium containing staurosporine and graded concentrations of glucose to manipulate intracellular ATP levels. Under ATP-depleting conditions, the cell death caused by staurosporine was primarily necrotic, as determined by creatine kinase release and nuclear staining with ethidium homodimer-1. However, under ATP-replenishing conditions, staurosporine increased the percentage of apoptotic cells, as determined by nuclear morphology and DNA fragmentation. Caspase-3 activation by staurosporine was also ATP dependent. However, loss of mitochondrial transmembrane potential (DeltaPsi(m)), Bax translocation, and cytochrome c release were observed in both apoptotic and necrotic cells. Moreover, cyclosporin A, an inhibitor of mitochondrial permeability transition, attenuated staurosporine-induced apoptosis and necrosis through the inhibition of DeltaPsi(m) reduction, cytochrome c release, and caspase-3 activation. Our data therefore suggest that staurosporine induces cell demise through a mitochondrial death signaling pathway and that the presence of intracellular ATP favors a shift from necrosis to apoptosis through caspase activation. PMID:11557554

  4. Sex-dependent effects of maternal deprivation and adolescent cannabinoid treatment on adult rat behaviour.

    Science.gov (United States)

    Llorente-Berzal, Alvaro; Fuentes, Sílvia; Gagliano, Humberto; López-Gallardo, Meritxell; Armario, Antonio; Viveros, María-Paz; Nadal, Roser

    2011-10-01

    Early life experiences such as maternal deprivation (MD) exert long-lasting changes in adult behaviour and reactivity to stressors. Adolescent exposure to cannabinoids is a predisposing factor in developing certain psychiatric disorders. Therefore, the combination of the two factors could exacerbate the negative consequences of each factor when evaluated at adulthood. The objective of this study was to investigate the long-term effects of early MD [24 hours at postnatal day (PND) 9] and/or an adolescent chronic treatment with the cannabinoid agonist CP-55,940 (0.4 mg/kg, PND 28-42) on diverse behavioural and physiological responses of adult male and female Wistar rats. We tested them in the prepulse inhibition (PPI) of the startle response and analysed their exploratory activity (holeboard) and anxiety (elevated plus maze, EPM). In addition, we evaluated their adrenocortical reactivity in response to stress and plasma leptin levels. Maternal behaviour was measured before and after deprivation. MD induced a transient increase of maternal behaviour on reuniting. In adulthood, maternally deprived males showed anxiolytic-like behaviour (or increased risk-taking behaviour) in the EPM. Adolescent exposure to the cannabinoid agonist induced an impairment of the PPI in females and increased adrenocortical responsiveness to the PPI test in males. Both, MD and adolescent cannabinoid exposure also induced sex-dependent changes in plasma leptin levels and body weights. The present results indicate that early MD and adolescent cannabinoid exposure exerted distinct sex-dependent long-term behavioural and physiological modifications that could predispose to the development of certain neuropsychiatric disorders, though no synergistic effects were found.

  5. Feeding blueberry diets to young rats dose-dependently inhibits bone resorption through suppression of RANKL in stromal cells.

    Directory of Open Access Journals (Sweden)

    Jian Zhang

    Full Text Available Previous studies have demonstrated that weanling rats fed AIN-93G semi-purified diets supplemented with 10% whole blueberry (BB powder for two weeks beginning on postnatal day 21 (PND21 significantly increased bone formation at PND35. However, the minimal level of dietary BB needed to produce these effects is, as yet, unknown. The current study examined the effects of three different levels of BB diet supplementation (1, 3, and 5% for 35 days beginning on PND25 on bone quality, and osteoclastic bone resorption in female rats. Peripheral quantitative CT scan (pQCT of tibia, demonstrated that bone mineral density (BMD and content (BMC were dose-dependently increased in BB-fed rats compared to controls (P<0.05. Significantly increased bone mass after feeding 5% BB extracts was also observed in a TEN (total enteral nutrition rat model in which daily caloric and food intake was precisely controlled. Expression of RANKL (receptor activator of nuclear factor-κB ligand a protein essential for osteoclast formation was dose-dependently decreased in the femur of BB animals. In addition, expression of PPARγ (peroxisome proliferator-activated receptor γ which regulates bone marrow adipogenesis was suppressed in BB diet rats compared to non-BB diet controls. Finally, a set of in vitro cell cultures revealed that the inhibitory effect of BB diet rat serum on RANKL expression was more profound in mesenchymal stromal cells compared to its effect on mature osteoblasts, pre-adipocytes and osteocytes. These results suggest that inhibition of bone resorption may contribute to increased bone mass during early development after BB consumption.

  6. Heat shock protein 70-dependent protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells.

    Science.gov (United States)

    Qin, Ying; Naito, Yuji; Handa, Osamu; Hayashi, Natsuko; Kuki, Aiko; Mizushima, Katsura; Omatsu, Tatsushi; Tanimura, Yuko; Morita, Mayuko; Adachi, Satoko; Fukui, Akifumi; Hirata, Ikuhiro; Kishimoto, Etsuko; Nishikawa, Taichiro; Uchiyama, Kazuhiko; Ishikawa, Takeshi; Takagi, Tomohisa; Yagi, Nobuaki; Kokura, Satoshi; Yoshikawa, Toshikazu

    2011-11-01

    Protection of the small intestine from mucosal injury induced by nonsteroidal anti-inflammatory drugs including acetylsalicylic acid is a critical issue in the field of gastroenterology. Polaprezinc an anti-ulcer drug, consisting of zinc and L-carnosine, provides gastric mucosal protection against various irritants. In this study, we investigated the protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of the RIE1 rat intestinal epithelial cell line. Confluent rat intestinal epithelial cells were incubated with 70 µM polaprezinc for 24 h, and then stimulated with or without 15 mM acetylsalicylic acid for a further 15 h. Subsequent cellular viability was quantified by fluorometric assay based on cell lysis and staining. Acetylsalicylic acid-induced cell death was also qualified by fluorescent microscopy of Hoechst33342 and propidium iodide. Heat shock proteins 70 protein expression after adding polaprezinc or acetylsalicylic acid was assessed by western blotting. To investigate the role of Heat shock protein 70, Heat shock protein 70-specific small interfering RNA was applied. Cell viability was quantified by fluorometric assay based on cell lysis and staining and apoptosis was analyzed by fluorescence-activated cell sorting. We found that acetylsalicylic acid significantly induced apoptosis of rat intestinal epithelial cells in a dose- and time-dependent manner. Polaprezinc significantly suppressed acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells at its late phase. At the same time, polaprezinc increased Heat shock protein 70 expressions of rat intestinal epithelial cells in a time-dependent manner. However, in Heat shock protein 70-silenced rat intestinal epithelial cells, polaprezinc could not suppress acetylsalicylic acid -induced apoptosis at its late phase. We conclude that polaprezinc-increased Heat shock protein 70 expression might be an important mechanism by which polaprezinc suppresses acetylsalicylic

  7. Voxel Scale Complex Networks of Functional Connectivity in the Rat Brain: Neurochemical State Dependence of Global and Local Topological Properties

    Directory of Open Access Journals (Sweden)

    Adam J. Schwarz

    2012-01-01

    Full Text Available Network analysis of functional imaging data reveals emergent features of the brain as a function of its topological properties. However, the brain is not a homogeneous network, and the dependence of functional connectivity parameters on neuroanatomical substrate and parcellation scale is a key issue. Moreover, the extent to which these topological properties depend on underlying neurochemical changes remains unclear. In the present study, we investigated both global statistical properties and the local, voxel-scale distribution of connectivity parameters of the rat brain. Different neurotransmitter systems were stimulated by pharmacological challenge (d-amphetamine, fluoxetine, and nicotine to discriminate between stimulus-specific functional connectivity and more general features of the rat brain architecture. Although global connectivity parameters were similar, mapping of local connectivity parameters at high spatial resolution revealed strong neuroanatomical dependence of functional connectivity in the rat brain, with clear differentiation between the neocortex and older brain regions. Localized foci of high functional connectivity independent of drug challenge were found in the sensorimotor cortices, consistent with the high neuronal connectivity in these regions. Conversely, the topological properties and node roles in subcortical regions varied with neurochemical state and were dependent on the specific dynamics of the different functional processes elicited.

  8. The differences in learning abilities between spontaneously hypertensive (SHR) and Wistar normotensive rats are cue dependent.

    Science.gov (United States)

    Lukaszewska, I; Niewiadomska, G

    1995-01-01

    We examined the performance of spontaneously hypertensive (SHR) and Wistar normotensive (NT) rats in acquisition, retention after a 2-month interval, and reversal learning in two tasks: simultaneous brightness discrimination (Experiment I) and conditional discrimination of directional locomotor responses (Experiment II). In both tasks food reinforcement was used. In Experiment I both SHR and NT groups comprised younger (3-month-old) and older (10-month-old) rats. In each experimental stage SHRs of both age groups mastered the task earlier and made fewer errors than the respective NT groups. Reversal learning took longer than acquisition of discrimination in both age groups of NT rats. Conversely, reversal learning was an easier task for SHR. In Experiment II only younger rats were used. The forced turn at the start in the modified T-maze was utilized as the cue to guide performance at the choice point of the maze. In acquisition and retention, rats were trained to select at the choice point the arm in the same direction as in the forced turn; in the reversal, opposite contingencies were applied. At all stages the choice accuracy of SHR was the same as that in NT rats. The contrasting findings of Experiment I and Experiment II indicate that SHR learned better than NT when exteroceptive visual stimuli were used, but performed at the same level as NT rats in the task where interoceptive kinesthetic cues were relevant. We suggest that SHR pay more attention to visual stimuli than NT rats. PMID:7663879

  9. Oxidative damage following cerebral ischemia depends on reperfusion - a biochemical study in rat

    DEFF Research Database (Denmark)

    Nita, D A; Nita, V; Spulber, S;

    2002-01-01

    and clearance. Wistar male rats were subject of four-vessel occlusion model (Pulsinelly & Brierley) cerebral blood flow being controlled by means of two atraumatic arterial microclamps placed on carotid arteries. The level of free radicals and the antioxidant activity were measured in ischemic rat brain tissue...

  10. Temperature-dependent variation in afferent nerve discharge in rat jejunum

    DEFF Research Database (Denmark)

    Gregersen, Hans; Yang, Jian; Zhao, Jingbo

    2015-01-01

    baseline discharge and on distension-induced afferent fibers innervating the rat jejunum. Methods: Multi-unit afferent activity was recorded in vitro from jejunum afferents from 9 Wistar rats. The segments were immersed in oxygenated Krebs solution varied between 21–43 °C. The mesenteric nerve bundle...

  11. Time-dependent expression profiles of microRNAs and mRNAs in rat milk whey.

    Directory of Open Access Journals (Sweden)

    Hirohisa Izumi

    Full Text Available Functional RNAs, such as microRNA (miRNA and mRNA, are present in milk, but their roles are unknown. To clarify the roles of milk RNAs, further studies using experimental animals such as rats are needed. However, it is unclear whether rat milk also contains functional RNAs and what their time dependent expression profiles are. Thus, we prepared total RNA from whey isolated from rat milk collected on days 2, 9, and 16 postpartum and analyzed using microarrays and quantitative PCR. The concentration of RNA in colostrum whey (day 2 was markedly higher than that in mature milk whey (days 9 and 16. Microarray analysis detected 161 miRNAs and 10,948 mRNA transcripts. Most of the miRNAs and mRNA transcripts were common to all tested milks. Finally, we selected some immune- and development-related miRNAs and mRNAs, and analysed them by quantitative PCR (in equal sample volumes to determine their time-dependent changes in expression in detail. Some were significantly more highly expressed in colostrum whey than in mature milk whey, but some were expressed equally. And mRNA expression levels of some cytokines and hormones did not reflect the protein levels. It is still unknown whether RNAs in milk play biological roles in neonates. However, our data will help guide future in vivo studies using experimental animals such as rats.

  12. The Eag domain regulates the voltage-dependent inactivation of rat Eag1 K+ channels.

    Directory of Open Access Journals (Sweden)

    Ting-Feng Lin

    Full Text Available Eag (Kv10 and Erg (Kv11 belong to two distinct subfamilies of the ether-à-go-go K+ channel family (KCNH. While Erg channels are characterized by an inward-rectifying current-voltage relationship that results from a C-type inactivation, mammalian Eag channels display little or no voltage-dependent inactivation. Although the amino (N-terminal region such as the eag domain is not required for the C-type inactivation of Erg channels, an N-terminal deletion in mouse Eag1 has been shown to produce a voltage-dependent inactivation. To further discern the role of the eag domain in the inactivation of Eag1 channels, we generated N-terminal chimeras between rat Eag (rEag1 and human Erg (hERG1 channels that involved swapping the eag domain alone or the complete cytoplasmic N-terminal region. Functional analyses indicated that introduction of the homologous hERG1 eag domain led to both a fast phase and a slow phase of channel inactivation in the rEag1 chimeras. By contrast, the inactivation features were retained in the reverse hERG1 chimeras. Furthermore, an eag domain-lacking rEag1 deletion mutant also showed the fast phase of inactivation that was notably attenuated upon co-expression with the rEag1 eag domain fragment, but not with the hERG1 eag domain fragment. Additionally, we have identified a point mutation in the S4-S5 linker region of rEag1 that resulted in a similar inactivation phenotype. Biophysical analyses of these mutant constructs suggested that the inactivation gating of rEag1 was distinctly different from that of hERG1. Overall, our findings are consistent with the notion that the eag domain plays a critical role in regulating the inactivation gating of rEag1. We propose that the eag domain may destabilize or mask an inherent voltage-dependent inactivation of rEag1 K+ channels.

  13. Apolipoprotein B of low-density lipoprotein impairs nitric oxide-mediated endothelium-dependent relaxation in rat mesenteric arteries

    DEFF Research Database (Denmark)

    Zhang, Yaping; Zhang, Wei; Edvinsson, Lars;

    2014-01-01

    Apolipoprotein B (ApoB) of low-density lipoprotein (LDL) causes endothelial dysfunction in the initial stage of atherogenesis. The present study was designed to explore the underlying molecular mechanisms involved. Rat mesenteric arteries were organ cultured in the presence of different concentra......B of LDL impairs vasodilation with damaging the endothelium and attenuating the NO-mediated endothelium-dependent relaxation, which might associate with lipid peroxidation and contribute to the development of cardiovascular disease....

  14. Role of afferent input in load-dependent plasticity of rat muscle

    Science.gov (United States)

    Kawano, F.; Umemoto, S.; Higo, Y.; Kawabe, N.; Wang, X. D.; Lan, Y. B.; Ohira, Y.

    We have been studying the role of afferent input in the plasticity of skeletal muscles. The present study was performed to investigate the mechanisms responsible for the deafferentation-related inhibition of the compensatory hypertrophy in rat soleus muscle. Adult male Wistar rats were randomly separated into the control, functionally overloaded (FO), and functionally overloaded + deafferentation (FO+DA) group. The tendons of plantaris and gastrocnemius muscles were transected in the FO rats. The dorsal roots of the spinal cord at the L4-5 segmental levels were additionally transected in the FO+DA rats. The sampling of the soleus was performed 2 weeks after the surgery and ambulation recovery. The single muscle fibers were isolated in low-calcium relaxing solution. Further, the myonuclei or argyrophilic nucleolar organizer regions (AgNORs) were stained. Significant increase of the fiber cross-sectional area (CSA) was seen in the FO, but not in the FO+DA, rats. The myonuclear number in fiber was significantly decreased by FO. Addition of DA to FO further promoted the reduction of myonuclear number. The mean nucleus size and DNA content in single nucleus in all groups were identical. Although a single or double AgNORs were seen in ~90% of myonuclei in the control rats, their distributions were 72 and 76% in the FO and FO+DA rats, respectively (phypertrophy. It was also indicated that intact afferent input plays an essential role in these phenomena.

  15. Assessment of tumor vascularization with functional computed tomography perfusion imaging in patients with cirrhotic liver disease

    Institute of Scientific and Technical Information of China (English)

    Jin-Ping Li; De-Li Zhao; Hui-Jie Jiang; Ya-Hua Huang; Da-Qing Li; Yong Wan; Xin-Ding Liu; Jin-E Wang

    2011-01-01

    BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor in China, and early diagnosis is critical for patient outcome. In patients with HCC, it is mostly based on liver cirrhosis, developing from benign regenerative nodules and dysplastic nodules to HCC lesions, and a better understanding of its vascular supply and the hemodynamic changes may lead to early tumor detection. Angiogenesis is essential for the growth of primary and metastatic tumors due to changes in vascular perfusion, blood volume and permeability. These hemodynamic and physiological properties can be measured serially using functional computed tomography perfusion (CTP) imaging and can be used to assess the growth of HCC. This study aimed to clarify the physiological characteristics of tumor angiogenesis in cirrhoticliverdiseasebythisfastimagingmethod. METHODS: CTP was performed in 30 volunteers without liver disease (control subjects) and 49 patients with liver disease (experimental subjects: 27 with HCC and 22 with cirrhosis). All subjects were also evaluated by physical examination, laboratory screening and Doppler ultrasonography of the liver. The diagnosis of HCC was made according to the EASL criteria. All patients underwent contrast-enhanced ultrasonography, pre- and post-contrast triple-phase CT and CTP study. A mathematical deconvolution model was applied to provide hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT), permeability of capillary vessel surface (PS), hepatic arterial index (HAI), hepatic arterial perfusion (HAP) and hepatic portal perfusion (HPP) data. The Mann-Whitney U test was used to determine differences in perfusion parameters between the background cirrhotic liver parenchyma and HCC and between the cirrhotic liver parenchyma with HCC and that without HCC. RESULTS: In normal liver, the HAP/HVP ratio was about 1/4. HCC had significantly higher HAP and HAI and lower HPP than background liver parenchyma adjacent to the HCC. The

  16. Hydrolysis-dependent absorption of disaccharides in the rat small intestine (chronic experiments and mathematical modeling).

    Science.gov (United States)

    Gromova, L V; Gruzdkov, A A

    1999-06-01

    In order to throw light on the mechanisms responsible for the enzyme-dependent absorption of disaccharides membrane hydrolysis of maltose and trehalose and the absorption of glucose (free and that derived from disaccharides) were studied in isolated loops (20 cm) of the rat small intestine in chronic experiments. The rates of glucose absorption were 0.26-0.81 micromol x min(-1) x cm(-1) when the loop was perfused with a 12.5 to 75.0 mmol/l free glucose solution, which is only insignificantly higher than the rates observed during perfusion with equivalent maltose solutions. The coupling coefficient (the ratio of glucose absorption rate to the rate of disaccharide hydrolysis) decreased from 0.90 to 0.60 with the increasing maltose concentrations in the infusate from 6.25 to 37.5 mmol/l, but remained unchanged (approximately 0.95) within the same range of trehalose concentrations. The permeability of the pre-epithelial barrier was equivalent to that of unstirred water layer of less than 40 microm thickness. Fluid absorption was within the range of 0.73-2.55 microl x min(-1) x cm(-1), and it showed a correlation with the rates of glucose absorption. The results agree with a model developed on the assumption that free glucose and that released from disaccharides share the same membrane transporters. It could be concluded that a close coupling of disaccharide hydrolysis with derived glucose absorption in chronic experiments is achieved mainly due to a high activity of glucose transporters, which are presumably not associated with membrane disaccharidases. The transcellular active transport is a predominant mechanism of disaccharide-derived glucose absorption under conditions close to physiological.

  17. Chronic uranium exposure dose-dependently induces glutathione in rats without any nephrotoxicity.

    Science.gov (United States)

    Poisson, C; Stefani, J; Manens, L; Delissen, O; Suhard, D; Tessier, C; Dublineau, I; Guéguen, Y

    2014-10-01

    Uranium is a heavy metal naturally found in the earth's crust that can contaminate the general public population when ingested. The acute effect and notably the uranium nephrotoxicity are well known but knowledge about the effect of chronic uranium exposure is less clear. In a dose-response study we sought to determine if a chronic exposure to uranium is toxic to the kidneys and the liver, and what the anti-oxidative system plays in these effects. Rats were contaminated for 3 or 9 months by uranium in drinking water at different concentrations (0, 1, 40, 120, 400, or 600 mg/L). Uranium tissue content in the liver, kidneys, and bones was linear and proportional to uranium intake after 3 and 9 months of contamination; it reached 6 μg per gram of kidney tissues for the highest uranium level in drinking water. Nevertheless, no histological lesions of the kidney were observed, nor any modification of kidney biomarkers such as creatinine or KIM-1. After 9 months of contamination at and above the 120-mg/L concentration of uranium, lipid peroxidation levels decreased in plasma, liver, and kidneys. Glutathione concentration increased in the liver for the 600-mg/L group, in the kidney it increased dose dependently, up to 10-fold, after 9 months of contamination. Conversely, chronic uranium exposure irregularly modified gene expression of antioxidant enzymes and activities in the liver and kidneys. In conclusion, chronic uranium exposure did not induce nephrotoxic effects under our experimental conditions, but instead reinforced the antioxidant system, especially by increasing glutathione levels in the kidneys.

  18. Morphine dependence and dopaminergic activity: tests of circling responses in rats with unilateral nigral lesions.

    OpenAIRE

    Halliwell, J. V.; Kumar, R.

    1980-01-01

    1 Rats with unilateral electrolytic lesions involving both parts of the substantia nigra show dose-related, ipsilateral circling responses to apomorphine which are stable over time. 2 In non-tolerant rats, morphine (up to 10 mg/kg) does not elicit any circling behaviour but as tolerance develops to morphine, initially 10 mg/kg daily and then 100 ng/kg daily for about 4 months, the rats show a progressive tendency to walk more towards the side of the lesion. This behaviour is qualitatively dif...

  19. Peripubertal Caffeine Exposure Impairs Longitudinal Bone Growth in Immature Male Rats in a Dose- and Time-Dependent Manner.

    Science.gov (United States)

    Choi, Yun-Young; Choi, Yuri; Kim, Jisook; Choi, Hyeonhae; Shin, Jiwon; Roh, Jaesook

    2016-01-01

    This study investigated the dose- and time-dependent effects of caffeine consumption throughout puberty in peripubertal rats. A total of 85 male SD rats were randomly divided into four groups: control and caffeine-fed groups with 20, 60, or 120 mg/kg/day through oral gavage for 10, 20, 30, or 40 days. Caffeine decreased body weight gain and food consumption in a dose- and time-dependent manner, accompanied by a reduction in muscle and body fat. In addition, it caused a shortening and lightening of leg bones and spinal column. The total height of the growth plate decreased sharply at 40 days in the controls, but not in the caffeine-fed groups, and the height of hypertrophic zone in the caffeine-fed groups was lower than in the control. Caffeine increased the height of the secondary spongiosa, whereas parameters related to bone formation, such as bone area ratio, thickness and number of trabeculae, and bone perimeter, were significantly reduced. Furthermore, serum levels of IGF-1, estradiol, and testosterone were also reduced by the dose of caffeine exposure. Our results demonstrate that caffeine consumption can dose- and time-dependently inhibit longitudinal bone growth in immature male rats, possibly by blocking the physiologic changes in body composition and hormones relevant to bone growth.

  20. Prediction and evaluation of route dependent dosimetry of BPA in rats at different life stages using a physiologically based pharmacokinetic model

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xiaoxia, E-mail: Xiaoxia.Yang@fda.hhs.gov; Doerge, Daniel R.; Fisher, Jeffrey W.

    2013-07-01

    Bisphenol A (BPA) has received considerable attention throughout the last decade due to its widespread use in consumer products. For the first time a physiologically based pharmacokinetic (PBPK) model was developed in neonatal and adult rats to quantitatively evaluate age-dependent pharmacokinetics of BPA and its phase II metabolites. The PBPK model was calibrated in adult rats using studies on BPA metabolism and excretion in the liver and gastrointestinal tract, and pharmacokinetic data with BPA in adult rats. For immature rats the hepatic and gastrointestinal metabolism of BPA was inferred from studies on the maturation of phase II enzymes coupled with serum time course data in pups. The calibrated model predicted the measured serum concentrations of BPA and BPA conjugates after administration of 100 μg/kg of d6-BPA in adult rats (oral gavage and intravenous administration) and postnatal days 3, 10, and 21 pups (oral gavage). The observed age-dependent BPA serum concentrations were partially attributed to the immature metabolic capacity of pups. A comparison of the dosimetry of BPA across immature rats and monkeys suggests that dose adjustments would be necessary to extrapolate toxicity studies from neonatal rats to infant humans. - Highlights: • A PBPK model predicts the kinetics of bisphenol A (BPA) in young and adult rats. • BPA metabolism within enterocytes is required for fitting of oral BPA kinetic data. • BPA dosimetry in young rats is different than adult rats and young monkeys.

  1. Glutamate co-transmission from developing medial nucleus of the trapezoid body - Lateral superior olive synapses is cochlear dependent in kanamycin-treated rats

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Ho [Institute of Tissue Regeneration Engineering (ITREN), Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of); Pradhan, Jonu [Department of Nanobio Medical Science, Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of); Maskey, Dhiraj; Park, Ki Sup [Department of Anatomy, College of Medicine, Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of); Hong, Sung Hwa [Department of Otorhinolaryngology-Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University, School of Medicine, 50, Irwon-dong, Gangnam-gu, Seoul 135-710 (Korea, Republic of); Suh, Myung-Whan [Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of); Kim, Myeung Ju, E-mail: mjukim99@dankook.ac.kr [Department of Anatomy, College of Medicine, Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of); Ahn, Seung Cheol, E-mail: ansil67@hanmail.net [Department of Physiology, College of Medicine, Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of)

    2011-02-11

    Research highlights: {yields} Glutamate co-transmission is enhanced in kanamycin-treated rats. {yields} VGLUT3 expression is increased in kanamycin-treated rats. {yields} GlyR expression is decreased in kanamycin-treated rats. {yields} GlyR, VGLUT3 expression patterns are asymmetric in unilaterally cochlear ablated rat. -- Abstract: Cochlear dependency of glutamate co-transmission at the medial nucleus of the trapezoid body (MNTB) - the lateral superior olive (LSO) synapses was investigated using developing rats treated with high dose kanamycin. Rats were treated with kanamycin from postnatal day (P) 3 to P8. A scanning electron microscopic study on P9 demonstrated partial cochlear hair cell damage. A whole cell voltage clamp experiment demonstrated the increased glutamatergic portion of postsynaptic currents (PSCs) elicited by MNTB stimulation in P9-P11 kanamycin-treated rats. The enhanced VGLUT3 immunoreactivities (IRs) in kanamycin-treated rats and asymmetric VGLUT3 IRs in the LSO of unilaterally cochlear ablated rats supported the electrophysiologic data. Taken together, it is concluded that glutamate co-transmission is cochlear-dependent and enhanced glutamate co-transmission in kanamycin-treated rats is induced by partial cochlear damage.

  2. Flaxseed Protects Against Diabetes-Induced Glucotoxicity by Modulating Pentose Phosphate Pathway and Glutathione-Dependent Enzyme Activities in Rats.

    Science.gov (United States)

    Gök, Müslüm; Ulusu, Nuray N; Tarhan, Nilay; Tufan, Can; Ozansoy, Gülgün; Arı, Nuray; Karasu, Çimen

    2016-01-01

    This study investigated the effects of flaxseed (Linum usitatissimum L.) intake on general metabolism, pentose phosphate pathway (PPP) and glutathione-dependent enzymes in diabetic rats. Diabetes was induced by streptozotocin injection (40 mg/kg, i.p.) and the enzyme activities were determined spectrophotometrically. Diabetic and control rats were divided in two subgroups, one untreated, and one treated with flaxseed (0.714 g/kg body weight/day; orally) for 12 weeks. Flaxseed ameliorated decreased body weight (p < .05) and increased blood glucose (p < .001), triglyceride (p < .001), ALT (p < .001) and AST (p < .001) in diabetic rats. Diabetes resulted in increased glucose-6-phosphate dehydrogenase (G6PD) (p < .05) and decreased glutathione-S-transferase (GST) (p < .01), but unchanged 6-phosphogluconate dehydrogenase (6PGD) and glutathione reductase (GR) in the brain of rats. These alterations were partially improved by flaxseed in comparison to diabetic untreated group (p < .05). G6PD, 6PGD, GR were elevated (p < .001), while GST unchanged in the lung of diabetic untreated group compared to control. Flaxseed partially prevented the increase in 6PGD (p < .05) and GR (p < .01), but unaffected G6PD in the lung of diabetic rats. G6PD (p < .001), 6PGD (p < .05), GR (p < .001) were augmented, while GST showed a significant (p < .001) depletion in the pancreas of diabetic untreated rats compared to control. Diabetic alterations observed in pancreatic enzyme activities were significantly prevented by flaxseed. Furthermore, a remarkable decrease in 6PGD (p < .001) and an increase in G6PD (threefold of control) were found in the lens of diabetic untreated group that were completely prevented by flaxseed (p < .001). Flaxseed has beneficial effects against diabetes-induced glucotoxicity by modulating G6PD, 6PGD, GR and GST activities in tissues.

  3. The delay in the development of experimental colitis from isomaltosyloligosaccharides in rats is dependent on the degree of polymerization.

    Directory of Open Access Journals (Sweden)

    Hitoshi Iwaya

    Full Text Available BACKGROUND: Isomaltosyloligosaccharides (IMO and dextran (Dex are hardly digestible in the small intestine and thus influence the luminal environment and affect the maintenance of health. There is wide variation in the degree of polymerization (DP in Dex and IMO (short-sized IMO, S-IMO; long-sized IMO, L-IMO, and the physiological influence of these compounds may be dependent on their DP. METHODOLOGY/PRINCIPAL FINDINGS: Five-week-old male Wistar rats were given a semi-purified diet with or without 30 g/kg diet of the S-IMO (DP = 3.3, L-IMO (DP = 8.4, or Dex (DP = 1230 for two weeks. Dextran sulfate sodium (DSS was administered to the rats for one week to induce experimental colitis. We evaluated the clinical symptoms during the DSS treatment period by scoring the body weight loss, stool consistency, and rectal bleeding. The development of colitis induced by DSS was delayed in the rats fed S-IMO and Dex diets. The DSS treatment promoted an accumulation of neutrophils in the colonic mucosa in the rats fed the control, S-IMO, and L-IMO diets, as assessed by a measurement of myeloperoxidase (MPO activity. In contrast, no increase in MPO activity was observed in the Dex-diet-fed rats even with DSS treatment. Immune cell populations in peripheral blood were also modified by the DP of ingested saccharides. Dietary S-IMO increased the concentration of n-butyric acid in the cecal contents and the levels of glucagon-like peptide-2 in the colonic mucosa. CONCLUSION/SIGNIFICANCE: Our study provided evidence that the physiological effects of α-glucosaccharides on colitis depend on their DP, linkage type, and digestibility.

  4. Differential Changes in Expression of Stress- and Metabolic-Related Neuropeptides in the Rat Hypothalamus during Morphine Dependence and Withdrawal.

    Directory of Open Access Journals (Sweden)

    Bernadett Pintér-Kübler

    Full Text Available Chronic morphine treatment and naloxone precipitated morphine withdrawal activates stress-related brain circuit and results in significant changes in food intake, body weight gain and energy metabolism. The present study aimed to reveal hypothalamic mechanisms underlying these effects. Adult male rats were made dependent on morphine by subcutaneous implantation of constant release drug pellets. Pair feeding revealed significantly smaller weight loss of morphine treated rats compared to placebo implanted animals whose food consumption was limited to that eaten by morphine implanted pairs. These results suggest reduced energy expenditure of morphine-treated animals. Chronic morphine exposure or pair feeding did not significantly affect hypothalamic expression of selected stress- and metabolic related neuropeptides - corticotropin-releasing hormone (CRH, urocortin 2 (UCN2 and proopiomelanocortin (POMC compared to placebo implanted and pair fed animals. Naloxone precipitated morphine withdrawal resulted in a dramatic weight loss starting as early as 15-30 min after naloxone injection and increased adrenocorticotrophic hormone, prolactin and corticosterone plasma levels in morphine dependent rats. Using real-time quantitative PCR to monitor the time course of relative expression of neuropeptide mRNAs in the hypothalamus we found elevated CRH and UCN2 mRNA and dramatically reduced POMC expression. Neuropeptide Y (NPY and arginine vasopressin (AVP mRNA levels were transiently increased during opiate withdrawal. These data highlight that morphine withdrawal differentially affects expression of stress- and metabolic-related neuropeptides in the rat hypothalamus, while relative mRNA levels of these neuropeptides remain unchanged either in rats chronically treated with morphine or in their pair-fed controls.

  5. ATP-dependent transport of statins by human and rat MRP2/Mrp2

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, Lucy C.J., E-mail: Luc_ellis@yahoo.co.uk [Section of Translational Medicine, Division of Applied Biology, Polwarth Building, Foresterhill, Aberdeen AB25 2ZD (United Kingdom); Hawksworth, Gabrielle M. [Section of Translational Medicine, Division of Applied Biology, Polwarth Building, Foresterhill, Aberdeen AB25 2ZD (United Kingdom); Weaver, Richard J. [Biologie Servier, Drug Safety Research Centre, 905 Route de Saran, 45520 Gidy (France)

    2013-06-01

    Multidrug resistance associated protein-2, MRP2 (human), Mrp2 (rat) are an efflux transporter, responsible for the transport of numerous endogenous and xenobiotic compounds including taurocholate, methotrexate and carboxydichlorofluorescein (CDF). The present study aims to characterise transport of statins by human and rat MRP2/Mrp2 using membrane and vesicle preparations. All statins tested (simvastatin, pravastatin, pitavastatin, fluvastatin, atorvastatin, lovastatin and rosuvastatin) stimulated vanadate-sensitive ATPase activity in membranes expressing human or rat MRP2/Mrp2, suggesting that all statins are substrates of human and rat MRP2/Mrp2. The substrate affinity (Km) of all statins for MRP2/Mrp2 was comparable and no correlation between lipophilicity (logD{sub 7.0}) and Km was seen. All statins also inhibited uptake of the fluorescent Mrp2 substrate, CDF (1 μM) into vesicles expressing human or rat MRP2/Mrp2 with similar IC{sub 50} values. Fitting of the inhibitory data to the hill slope equation, gave hill coefficients (h) of greater than one, suggesting that transport involved more than one binding site for inhibitors of MPR2 and Mrp2. We conclude that statins were transported by both human and rat MRP2/Mrp2 with similar affinity. Statins were also shown to compete with other substrates for transport by MRP2/Mrp2 and that this transport involved more than one binding site on the Mrp2/MRP2 protein. - Highlights: • We characterised MRP2 (human)/Mrp2 (rat)-mediated transport of statins. • We show statins were transported by human and rat MRP2/Mrp2. • Statins competed with a known substrate for transport by MRP2/Mrp2. • Competition involved more than one binding site on the MRP2/Mrp2 protein.

  6. Dependence on exogenous methionine of rat sarcoma and murine leukemia cells in culture.

    Science.gov (United States)

    Koziorowska, J; Pieńkowska, K; Tautt, J

    1980-01-01

    A comparative study was performed on methionine auxotrophy of rat sarcoma and murine leukemia cells taken directly from the organism and grown in culture in media lacking methionine or in which methionine was substituted by homocysteine. Methionine auxotrophy was observed in both kinds of cells. At low levels of methionine in the media containing homocysteine rat sarcoma cells showed an increase in growth. Addition of homocysteine to the media with low levels of methionine did not influence the survival of murine leukemia cells.

  7. ATP-dependent transport of statins by human and rat MRP2/Mrp2

    International Nuclear Information System (INIS)

    Multidrug resistance associated protein-2, MRP2 (human), Mrp2 (rat) are an efflux transporter, responsible for the transport of numerous endogenous and xenobiotic compounds including taurocholate, methotrexate and carboxydichlorofluorescein (CDF). The present study aims to characterise transport of statins by human and rat MRP2/Mrp2 using membrane and vesicle preparations. All statins tested (simvastatin, pravastatin, pitavastatin, fluvastatin, atorvastatin, lovastatin and rosuvastatin) stimulated vanadate-sensitive ATPase activity in membranes expressing human or rat MRP2/Mrp2, suggesting that all statins are substrates of human and rat MRP2/Mrp2. The substrate affinity (Km) of all statins for MRP2/Mrp2 was comparable and no correlation between lipophilicity (logD7.0) and Km was seen. All statins also inhibited uptake of the fluorescent Mrp2 substrate, CDF (1 μM) into vesicles expressing human or rat MRP2/Mrp2 with similar IC50 values. Fitting of the inhibitory data to the hill slope equation, gave hill coefficients (h) of greater than one, suggesting that transport involved more than one binding site for inhibitors of MPR2 and Mrp2. We conclude that statins were transported by both human and rat MRP2/Mrp2 with similar affinity. Statins were also shown to compete with other substrates for transport by MRP2/Mrp2 and that this transport involved more than one binding site on the Mrp2/MRP2 protein. - Highlights: • We characterised MRP2 (human)/Mrp2 (rat)-mediated transport of statins. • We show statins were transported by human and rat MRP2/Mrp2. • Statins competed with a known substrate for transport by MRP2/Mrp2. • Competition involved more than one binding site on the MRP2/Mrp2 protein

  8. Metformin impairs mitochondrial function in skeletal muscle of both lean and diabetic rats in a dose-dependent manner.

    Directory of Open Access Journals (Sweden)

    Bart Wessels

    Full Text Available Metformin is a widely prescribed drug for the treatment of type 2 diabetes. Previous studies have demonstrated in vitro that metformin specifically inhibits Complex I of the mitochondrial respiratory chain. This seems contraindicative since muscle mitochondrial dysfunction has been linked to the pathogenesis of type 2 diabetes. However, its significance for in vivo skeletal muscle mitochondrial function has yet to be elucidated. The aim of this study was to assess the effects of metformin on in vivo and ex vivo skeletal muscle mitochondrial function in a rat model of diabetes. Healthy (fa/+ and diabetic (fa/fa Zucker diabetic fatty rats were treated by oral gavage with metformin dissolved in water (30, 100 or 300 mg/kg bodyweight/day or water as a control for 2 weeks. After 2 weeks of treatment, muscle oxidative capacity was assessed in vivo using 31P magnetic resonance spectroscopy and ex vivo by measuring oxygen consumption in isolated mitochondria using high-resolution respirometry. Two weeks of treatment with metformin impaired in vivo muscle oxidative capacity in a dose-dependent manner, both in healthy and diabetic rats. Whereas a dosage of 30 mg/kg/day had no significant effect, in vivo oxidative capacity was 21% and 48% lower after metformin treatment at 100 and 300 mg/kg/day, respectively, independent of genotype. High-resolution respirometry measurements demonstrated a similar dose-dependent effect of metformin on ex vivo mitochondrial function. In conclusion, metformin compromises in vivo and ex vivo muscle oxidative capacity in Zucker diabetic fatty rats in a dose-dependent manner.

  9. Salt-induced epithelial-to-mesenchymal transition in Dahl salt-sensitive rats is dependent on elevated blood pressure

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Y.; Mu, J.J.; Liu, F.Q.; Ren, K.Y.; Xiao, H.Y. [Xi' an Jiaotong University, Medical College, First Affiliated Hospital, Cardiovascular Department, Xi' an, China, Cardiovascular Department, First Affiliated Hospital, Medical College, Xi' an Jiaotong University, Xi' an (China); Ministry of Education, Key Laboratory of Environment and Genes Related to Diseases, Xi' an, China, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi' an (China); Yang, Z. [Xi' an Jiaotong University, Medical College, First Affiliated Hospital, Department of Pathology, Xi' an, China, Department of Pathology, First Affiliated Hospital, Medical College, Xi' an Jiaotong University, Xi' an (China); Yuan, Z.Y. [Xi' an Jiaotong University, Medical College, First Affiliated Hospital, Cardiovascular Department, Xi' an, China, Cardiovascular Department, First Affiliated Hospital, Medical College, Xi' an Jiaotong University, Xi' an (China); Ministry of Education, Key Laboratory of Environment and Genes Related to Diseases, Xi' an, China, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi' an (China)

    2014-03-03

    Dietary salt intake has been linked to hypertension and cardiovascular disease. Accumulating evidence has indicated that salt-sensitive individuals on high salt intake are more likely to develop renal fibrosis. Epithelial-to-mesenchymal transition (EMT) participates in the development and progression of renal fibrosis in humans and animals. The objective of this study was to investigate the impact of a high-salt diet on EMT in Dahl salt-sensitive (SS) rats. Twenty-four male SS and consomic SS-13{sup BN} rats were randomized to a normal diet or a high-salt diet. After 4 weeks, systolic blood pressure (SBP) and albuminuria were analyzed, and renal fibrosis was histopathologically evaluated. Tubular EMT was evaluated using immunohistochemistry and real-time PCR with E-cadherin and alpha smooth muscle actin (α-SMA). After 4 weeks, SBP and albuminuria were significantly increased in the SS high-salt group compared with the normal diet group. Dietary salt intake induced renal fibrosis and tubular EMT as identified by reduced expression of E-cadherin and enhanced expression of α-SMA in SS rats. Both blood pressure and renal interstitial fibrosis were negatively correlated with E-cadherin but positively correlated with α-SMA. Salt intake induced tubular EMT and renal injury in SS rats, and this relationship might depend on the increase in blood pressure.

  10. Brain-Cocaine Concentrations Determine the Dose Self-Administered by Rats on a Novel Behaviorally Dependent Dosing Schedule

    Science.gov (United States)

    Zimmer, Benjamin A; Dobrin, Carson V; Roberts, David C S

    2011-01-01

    A novel behaviorally dependent dosing (BDD) schedule was used to examine the relationship between doses of cocaine self-administered by rats and brain drug levels within a session. The BDD schedule used a hold-down response to activate a syringe pump. The length of time the lever was held down determined the duration that the syringe pump was activated. In the first experiment, rats self-administered cocaine for daily 3 h sessions and brain levels of cocaine were modeled using well-established parameters. Although analysis revealed that rats self-administered doses within a predicted range, one extremely large dose was consistently observed at the beginning of each session when brain levels of cocaine were low. In the second experiment, we introduced a range of timeout periods (10–25 min) in order to produce variability in brain-cocaine concentrations. Animals self-administered larger doses immediately following each timeout period and the dose size was inversely correlated with the length of the timeout. These results show that the dose of cocaine that rats self-administer within a session is inversely related to the amount of drug on board. PMID:21849981

  11. Salt-induced epithelial-to-mesenchymal transition in Dahl salt-sensitive rats is dependent on elevated blood pressure

    International Nuclear Information System (INIS)

    Dietary salt intake has been linked to hypertension and cardiovascular disease. Accumulating evidence has indicated that salt-sensitive individuals on high salt intake are more likely to develop renal fibrosis. Epithelial-to-mesenchymal transition (EMT) participates in the development and progression of renal fibrosis in humans and animals. The objective of this study was to investigate the impact of a high-salt diet on EMT in Dahl salt-sensitive (SS) rats. Twenty-four male SS and consomic SS-13BN rats were randomized to a normal diet or a high-salt diet. After 4 weeks, systolic blood pressure (SBP) and albuminuria were analyzed, and renal fibrosis was histopathologically evaluated. Tubular EMT was evaluated using immunohistochemistry and real-time PCR with E-cadherin and alpha smooth muscle actin (α-SMA). After 4 weeks, SBP and albuminuria were significantly increased in the SS high-salt group compared with the normal diet group. Dietary salt intake induced renal fibrosis and tubular EMT as identified by reduced expression of E-cadherin and enhanced expression of α-SMA in SS rats. Both blood pressure and renal interstitial fibrosis were negatively correlated with E-cadherin but positively correlated with α-SMA. Salt intake induced tubular EMT and renal injury in SS rats, and this relationship might depend on the increase in blood pressure

  12. Non-cirrhotic portal hypertension with large regenerative nodules: A diagnostic challenge

    Institute of Scientific and Technical Information of China (English)

    Umberto Vespasiani Gentilucci; Antonio Picardi; Paolo Gallo; Giuseppe Perrone; Riccardo Del Vescovo; Giovanni Galati; Sandro Spataro; Chiara Mazzarelli; Adriano Pellicelli; Antonella Afeltra

    2011-01-01

    Non-cirrhotic portal hypertension is a poorly understood condition characterized by portal hypertension in the absence of conventional hepatic cirrhosis and described in association with blood coagulation disorders, myeloproliferative and immunological diseases and with exposure to toxic drugs. Very recently, precise classification criteria have been proposed in order to define four distinct subcategories. The present case highlights how the clinical presentation, the confounding results from imaging studies, and the difficulties in the histological evaluation often render cases of non-cirrhotic portal hypertension a real diagnostic challenge. It also underscores the classification problems which can be faced once this diagnosis is performed. Indeed, the different subcategories proposed result from the prevalent subtypes in a spectrum of hepatic regenerative responses to a variety of injuries determining microcirculatory disturbances. More flexibility in classification should derive from this etiopathogenic background.

  13. Pathogenesis of hepatocarcinogenesis in non-cirrhotic nonalcoholic fatty liver disease:Potential mechanistic pathways

    Institute of Scientific and Technical Information of China (English)

    Ryan; B; Perumpail; Andy; Liu; Robert; J; Wong; Aijaz; Ahmed; Stephen; A; Harrison

    2015-01-01

    Although hepatocellular carcinoma(HCC) primarily arises in the background of liver cirrhosis,the development of HCC in nonalcoholic fatty liver disease(NAFLD) without cirrhosis is increasingly recognized. The pathogenesis of NAFLD associated non-cirrhotic HCC is distinct from that of cirrhotic HCC because the metabolic syndrome(MS) along with obesity and insulin resistance(IR) underlie several unique mechanisms that promote tumorigenesis. IR associated with MS,NAFLD,and type 2 diabetes mellitus lead to the release of multiple pro-inflammatory cytokines,including tumor necrosis factor alpha,interleukin-6,leptin and resistin,as well as decreased amounts of adiponectin. These processes favor the development of hepatic steatosis and inflammation within the liver,which precede HCC development. Nevertheless,further investigation is necessary to elucidate the determinants for development of HCC in patients with NAFLD in the absence of cirrhosis.

  14. Dietary resistant starch dose-dependently reduces adiposity in obesity-prone and obesity-resistant male rats

    Directory of Open Access Journals (Sweden)

    Belobrajdic Damien P

    2012-10-01

    Full Text Available Abstract Background Animal studies show that diets containing resistant starch (RS at levels not achievable in the human diet result in lower body weight and/or adiposity in rodents. We aimed to determine whether RS dose-dependently reduces adiposity in obesity-prone (OP and obesity-resistant (OR rats. Methods Male Sprague–Dawley rats (n=120 were fed a moderate-fat, high-energy diet for 4 wk. Rats that gained the most weight (40% were classified as obesity-prone (OP and obesity-resistant (OR rats were the 40% that gained the least weight. OP and OR rats were randomly allocated to one of six groups (n=8 for each phenotype. One group was killed for baseline measurements, the other five groups were allocated to AIN-93 based diets that contained 0, 4, 8, 12 and 16% RS (as high amylose maize starch for 4 wk. These diets were matched for total carbohydrate content. At 0, 4 and 7 wk from the start of the study insulin sensitivity was calculated by homeostasis model assessment of insulin resistance (HOMA-IR and adiposity was determined by dual-energy X-ray absorptiometry (DXA. At 8 wk, rats were euthanized and fat pad weights, intestinal digesta short chain fatty acid (SCFA pools and plasma gut hormone levels were determined. Results Obesity prone rats gained less weight with 4, 12 and 16% RS compared to 0% RS, but the effect in OR animals was significant only at 16% RS. Irrespective of phenotype, diets containing ≥8% RS reduced adiposity compared to 0% RS. Energy intake decreased by 9.8 kJ/d for every 4% increase in RS. All diets containing RS increased total SCFA pools in the caecum and lowered plasma GIP concentrations compared to the 0% RS, whereas plasma GLP-1 and PYY were increased when the diet contained at least 8% RS. Insulin sensitivity was not affected by RS. Conclusion RS in amounts that could be potentially consumed by humans were effective in reducing adiposity and weight gain in OP and OR rats, due in part to a reduction in energy

  15. Dependence of the Startle Response on Temporal and Spectral Characteristics of Acoustic Modulatory Influences in Rats and Gerbils

    Science.gov (United States)

    Steube, Natalie; Nowotny, Manuela; Pilz, Peter K. D.; Gaese, Bernhard H.

    2016-01-01

    The acoustic startle response (ASR) and its modulation by non-startling prepulses, presented shortly before the startle-eliciting stimulus, is a broadly applied test paradigm to determine changes in neural processing related to auditory or psychiatric disorders. Modulation by a gap in background noise as a prepulse is especially used for tinnitus assessment. However, the timing and frequency-related aspects of prepulses are not fully understood. The present study aims to investigate temporal and spectral characteristics of acoustic stimuli that modulate the ASR in rats and gerbils. For noise-burst prepulses, inhibition was frequency-independent in gerbils in the test range between 4 and 18 kHz. Prepulse inhibition (PPI) by noise-bursts in rats was constant in a comparable range (8–22 kHz), but lower outside this range. Purely temporal aspects of prepulse–startle-interactions were investigated for gap-prepulses focusing mainly on gap duration. While very short gaps had no (rats) or slightly facilitatory (gerbils) influence on the ASR, longer gaps always had a strong inhibitory effect. Inhibition increased with durations up to 75 ms and remained at a high level of inhibition for durations up to 1000 ms for both, rats and gerbils. Determining spectral influences on gap-prepulse inhibition (gap-PPI) revealed that gerbils were unaffected in the limited frequency range tested (4–18 kHz). The more detailed analysis in rats revealed a variety of frequency-dependent effects. Gaps in pure-tone background elicited constant and high inhibition (around 75%) over a broad frequency range (4–32 kHz). For gaps in noise-bands, on the other hand, a clear frequency-dependency was found: inhibition was around 50% at lower frequencies (6–14 kHz) and around 70% at high frequencies (16–20 kHz). This pattern of frequency-dependency in rats was specifically resulting from the inhibitory effect by the gaps, as revealed by detailed analysis of the underlying startle amplitudes. An

  16. Age-dependent pharmacokinetic and pharmacodynamic response in preweanling rats following oral exposure to the organophosphorus insecticide chlorpyrifos

    Energy Technology Data Exchange (ETDEWEB)

    Timchalk, Chuck; Poet, Torka S.; Kousba, Ahmed A.

    2006-03-01

    Juvenile rats are more susceptible than adults to the acute toxicity of organophosphorus insecticides like chlorpyrifos (CPF). Age- and dose-dependent differences in metabolism may be responsible. Of importance is CYP450 activation and detoxification of CPF to CPF-oxon and 3,5,6-trichloro-2-pyridinol (TCP), as well as B-esterase (cholinesterase; ChE) and A-esterase (PON-1) detoxification of CPF-oxon to TCP. The pharmacokinetics of CPF, TCP, and the extent of blood (plasma/RBC), and brain ChE inhibition in rats were determined on postnatal days (PND) -5, -12, and -17 following oral gavage administration of 1 and 10 mg CPF/kg of body weight. For all neonatal ages the blood TCP exceeded the CPF concentration, and within each age group there was no evidence of non-linear kinetics over the dose range evaluated. Younger animals demonstrated a greater sensitivity to ChE inhibition as evident by the dose- and age-dependent inhibition of plasma, RBC, and brain ChE. Of particular importance was the observation that even in rats as young as PND-5, the CYP450 metabolic capacity was adequate to metabolize CPF to both TCP and CPF-oxon based on the detection of TCP in blood and extensive ChE inhibition (biomarker of CPF-oxon) at all ages. In addition, the increase in the blood TCP concentration ({approx}3-fold) in PND-17 rats relative to the response in the younger animals, and the higher blood concentrations of CPF in neonatal rats (1.7 to 7.5-fold) relative to adults was consistent with an increase in CYP450 metabolic capacity with age. This is the first reported study that evaluated both the pharmacokinetics of the parent pesticide, the major metabolite and the extent of ChE inhibition dynamics in the same animals as a function of neonatal age. The results suggest that in the neonatal rat, CPF was rapidly absorbed and metabolized, and the extent of metabolism was age-dependent.

  17. Portal vein thrombosis: Etiology and clinical outcome of cirrhosis and malignancy-related non-cirrhotic, non-tumoral extrahepatic portal venous obstruction

    OpenAIRE

    Jain, Pankaj; Nijhawan, Sandeep

    2007-01-01

    The etiology and pathogenesis of portal vein thrombosis are unclear. Portal venous thrombosis presentation differs in cirrhotic and tumor-related versus non-cirrhotic and non-tumoral extrahepatic portal venous obstruction (EHPVO). Non-cirrhotic and non-tumoral EHPVO patients are young and present with well tolerated bleeding. Cirrhosis and tumor-related portal vein thrombosis patients are older and have a grim prognosis. Among the 118 patients with portal vein thrombosis, 15.3% had cirrhosis,...

  18. A Pleuroperitoneal Bleb Mimicking an Intrathoracic Mass in a Cirrhotic Patient: Three Case Reports

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jun Ho; Lee, Kyung Hee; Cho, Soon Gu; Jeon, Yong Sun [Inha University Hospital, Incheon (Korea, Republic of)

    2009-07-15

    In a cirrhotic patient, an increase in intra-abdominal pressure due to the presence of ascites might lead to a small pleuroperitoneal bleb of the peritoneum from congenital defects in the hemithorax. This lesion may appear as an intrathoracic mass as seen on a simple chest radiograph. A CT image may be helpful to differentiate an ascitic pleuroperitoneal bleb from an intrathoracic mass. We present three cases of a pleuroperitoneal bleb in patients with liver cirrhosis and ascites.

  19. Prognostic factors associated with rebleeding in cirrhotic inpatients complicated with esophageal variceal bleeding

    Institute of Scientific and Technical Information of China (English)

    WANG Mei-tang; LIU Tao; MA Xiu-qiang; HE Jian

    2011-01-01

    Background Esophageal variceal bleeding is a frequent and severe complication in patients with cirrhosis. The aim of this study was to identify prognostic factors of esophageal variceal rebleeding in cirrhotic inpatients.Methods Consecutive cirrhotic patients who were admitted to Changhai Hospital because of esophageal variceal bleeding were retrospectively analyzed. To assess the independent factors for recurrent hemorrhage after esophageal variceal bleeding, medical assessment was completed at the time of their initial hospital admission, including documentation of clinical, biochemical, and treatment methods that might contribute to variceal rebleeding. Univariate and multivariate analyses were retrospectively performed.Results Totally 186 patients (35.8%) were assigned to a rebleeding group and the other 334 patients (64.2%) to a non-rebleeding group. Multivariate stepwise regression analysis showed that four variables were positively correlated with rebleeding: Child-pugh grade B (OR=2.664, 95% CI 1.680-4.223) (compared with Child-pugh grade A), total bilirubin (Tbil) (OR=1.0006, 95% CI 1.002-1.0107), creatinine (OR=1.008, 95% CI 1.002-1.015) and the cumulative volume of blood transfusion (OR=1.519, 95% CI 1.345-1.716). The presence of ascites (OR=0.270, 95% CI 0.136-0.536) and prophylactic antibiotics (OR=0.504, 95% CI 0.325-0.780) were negatively correlated with rebleeding of the cirrhotic inpatients. According to standardized coefficient, the importance of rebleeding predictors ranked from the most to the least was as follows: the cumulative volume of blood transfusion, Child-pugh grade B, Tbil and creatinine.Conclusion Rebleeding in cirrhotic inpatients was associated with more blood transfusions, Child-pugh grade B, higher Tbil and creatinine.

  20. Non Insulin Dependent Diabetes in Sand Rat (Psammomys obesus) and Production of Collagen in Cultured Aortic Smooth Muscle Cells. Influence of Insulin

    OpenAIRE

    Bouguerra, S. Aouichat; Bourdillon, M. C.; Dahmani, Y.; Bekkhoucha, F.

    2001-01-01

    In this report, we have shown that the standard laboratory diet administered to Psammomys obesus (sand rat) from Beni Abbes in Algeria, induced a non-insulin dependant diabetes, characterised by increase of body weight (p

  1. Appropriate empirical antibiotic use and 30-d mortality in cirrhotic patients with bacteremia

    Science.gov (United States)

    Park, Hyun; Jang, Ki Jun; Jang, Won; Park, Sang Hoon; Park, Ji Young; Jeon, Tae Joo; Oh, Tae Hoon; Shin, Won Chang; Choi, Won-Choong; Sinn, Dong Hyun

    2015-01-01

    AIM: To analyze whether prompt and appropriate empirical antibiotic (AEA) use is associated with mortality in cirrhotic patients with bacteremia. METHODS: A total of 102 episodes of bacteremia in 72 patients with cirrhosis were analyzed. AEA was defined as a using or starting an antibiotic appropriate to the isolated pathogen at the time of bacteremia. The primary endpoint was 30-d mortality. RESULTS: The mortality rate at 30 d was 30.4% (31/102 episodes). Use of AEA was associated with better survival at 30 d (76.5% vs 46.9%, P = 0.05), and inappropriate empirical antibiotic (IEA) use was an independent factor associated with increased mortality (OR = 3.24; 95%CI: 1.50-7.00; P = 0.003, adjusted for age, sex, Child-Pugh Class, gastrointestinal bleeding, presence of septic shock). IEA use was more frequent when the isolated pathogen was a multiresistant pathogen, and when infection was healthcare-related or hospital-acquired. CONCLUSION: AEA use was associated with increased survival of cirrhotic patients who developed bacteremia. Strategies for AEA use, tailored according to the local epidemiological patterns, are needed to improve survival of cirrhotic patients with bacteremia. PMID:25834324

  2. PREVALENCE OF BACTERIAL RESISTANCE IN HOSPITALIZED CIRRHOTIC PATIENTS IN SOUTHERN BRAZIL: A NEW CHALLENGE

    Directory of Open Access Journals (Sweden)

    Ane Micheli COSTABEBER

    2016-01-01

    Full Text Available Background & Aims: An increased frequency of infections by multiresistant bacteria has been described in hospitalized patients. The aim of this study was to evaluate the bacterial resistance profile in cirrhotic patients. Methods: This is a retrospective observational study. We assessed the antimicrobial susceptibility of 5,839 bacterial isolates from patients with and without cirrhosis. Regarding the multidrug resistance, we evaluated 4,505 bacterial isolates from 2,180 patients. Results: Two hundred and fifty-one patients had cirrhosis (mean age 57.6 ± 11 years; 61.8% were male, 47.8% of cases associated with hepatitis C virus. Of the isolates of patients with and without cirrhosis, 174/464 (37.5% and 1,783/4,041 (44.1% were multiresistant, respectively (p = 0.007. E. coli was the most common multiresistant bacteria in both groups. Approximately 20% of E. coli and Klebsiella sp. isolates were ESBL-producers and 44% of S. aureus isolates were methicillin-resistant in cirrhotic patients. In cirrhotic patients admitted to the emergency department, hospital ward, and intensive care unit, 28.3%, 50% and 40% had multiresistant isolates, respectively. In patients with and without cirrhosis, 36.2% and 33.5% of isolates were resistant to third-generation cephalosporins, respectively. Conclusions: The empirical treatment of infections in hospitalized patients using broad-spectrum antibiotics should consider the observed pattern of bacterial resistance.

  3. Resistive index and MELD-Na: nephrologic monitoring in cirrhotic patients awaiting liver transplantation.

    Science.gov (United States)

    Umbro, I; Tinti, F; Fiacco, F; Zavatto, A; Piselli, P; Di Natale, V; Lai, S; Vitarelli, A; Corradini, S Ginanni; Rossi, M; Poli, L; Berloco, P B; Mitterhofer, A P

    2013-09-01

    Renal dysfunction in cirrhotic patients is primarily related to disturbances in circulatory function. In decompensated cirrhosis, ascites and water retention are associated with development of dilutional hyponatremia. The arterial resistive index (RI) is a measure of resistance to arterial flow within the renal vascular bed. Hyponatremia is an independent predictor of mortality in patients with ascites. The aim of this study was to evaluate intrarenal RI in end-stage liver disease (ESLD) patients awaiting liver transplantation (LT) and its association with renal and hepatic function as assessed by Model for End-Stage Liver Disease (MELD) and MELD-Na scores. We evaluated 40 cirrhotic patients (23 males, 17 females) awaiting LT from January 2009 to January 2012. Twenty-six of the 40 patients (65%) showed a renal RI ≥ 0.70, the normal value according to standard reported evaluations. Patients with RI ≥ 0.70 showed significantly higher MELD and MELD-Na scores as well as greater higher serum creatinine and lower serum sodium concentrations compared with subject displaying RI <0.70. The most relevant result of our study was the strong association between elevated renal RI in ESLD patients and advanced liver dysfunction, as demonstrated by MELD and MELD-Na scores, hyponatremia, ascites, and acute renal failure episodes. In conclusion, this study suggested that intrarenal RI assessment should be considered in the clinical and nephrologic monitoring of cirrhotic patients awaiting LT.

  4. Doppler study of hepatic vein in cirrhotic patients: Correlation with liver dysfunction and hepatic hemodynamics

    Institute of Scientific and Technical Information of China (English)

    KC Sudhamshu; Shoiichi Matsutani; Hitoshi Maruyama; Taro Akiike; Hiromitsu Saisho

    2006-01-01

    AIM: To elucidate the significance of Doppler measurements of hepatic vein in cirrhotic patients and to correlate with liver dysfunction and hepatic hemodynamics.METHODS: One hundred patients with liver cirrhosis and 60 non-cirrhotic controls were studied. Doppler waveforms were obtained from right hepatic vein and flow velocity measured during quiet respiration. Doppler measurements were also obtained from portal trunk,right portal vein and proper hepatic artery.RESULTS: Hepatic vein waveforms were classified into three classical patterns. Flat waveform was uncommon.Mean hepatic vein velocity was significantly higher in cirrhotic patients (12.7 ± 6.4 vs 5.1 ± 2.1 and 6.2 ± 3.2 cm/s; P < 0.0001). The poorer the grade of cirrhosis,the higher was the mean velocity. Maximum forward velocity was never greater than 40 cm/s in controls.Degree of ascites was found to be highly correlated with mean velocity. "Very high" group (≥ 20 cm/s) presented clinically with moderate to massive ascites. Correlations between right portal flow and mean velocity was significant (P < 0.0001, r = 0.687).CONCLUSION: Doppler waveforms of hepatic vein,which is independent of liver dysfunction, should be obtained during normal respiration. Mean hepatic vein velocity reflects the change in hepatic circulation associated with progression of liver cirrhosis. It can be used as a new parameter in the assessment of liver cirrhosis.

  5. Immunohistochemical assessment of angiogenesis in hepatocellular carcinoma and surrounding cirrhotic liver tissues

    Institute of Scientific and Technical Information of China (English)

    Geertu Deli; Can-Hao Jin; Rong Mu; Song Yang; Yue Liang; De Chen; Masatoshi Makuuchi

    2005-01-01

    AIM: To investigate whether vascular endothelial growth factor (VEGF) was over-expressed in hepatocellular carcinoma (HCC) or in surrounding cirrhotic liver tissues.METHODS: Immunohistochemistry was performed to investigate the expression of VEGF proteins in HCC tissues from 105 consecutive patients undergoing curative resection for HCC. The immunostaining results and related clinicopathologic materials were analyzed with statistical methods. Kaplan-Meier method was used to calculate survival curves, and Log-rank test was performed to compare differences in survival rates of the patients with positive HCC staining and negative VEGF.RESULTS: VEGF-positive expression was found in 72 of105 HCC patients (68.6%). Capsular infiltration (P= 0.005),vascular invasion (P = 0.035) and intrahepatic metastasis(P=0.008) were observed more frequently in patients with VEGF-positive expression than in those with VEGFnegative expression. Kaplan-Meier curves showed that VEGF-positive expression was associated with a shorter overall survival (P = 0.014). VEGF-positive expression was found in 47 of tissues 68 HCC (69.1%), and VEGF-positive expression was found in 54 of 68 surrounding cirrhotic liver tissues (79.4%). VEGF-positive expression was significantly higher in surrounding cirrhotic liver tissues than in HCC (P= 0.017).CONCLUSION: VEGF may play an important role in the angiogenesis and prognosis of HCC, as well as in the angiogenesis of liver cirrhosis.

  6. PREVALENCE OF BACTERIAL RESISTANCE IN HOSPITALIZED CIRRHOTIC PATIENTS IN SOUTHERN BRAZIL: A NEW CHALLENGE

    Science.gov (United States)

    COSTABEBER, Ane Micheli; de MATTOS, Angelo Alves; SUKIENNIK, Teresa Cristina Teixeira

    2016-01-01

    Background & Aims: An increased frequency of infections by multiresistant bacteria has been described in hospitalized patients. The aim of this study was to evaluate the bacterial resistance profile in cirrhotic patients. Methods: This is a retrospective observational study. We assessed the antimicrobial susceptibility of 5,839 bacterial isolates from patients with and without cirrhosis. Regarding the multidrug resistance, we evaluated 4,505 bacterial isolates from 2,180 patients. Results: Two hundred and fifty-one patients had cirrhosis (mean age 57.6 ± 11 years; 61.8% were male, 47.8% of cases associated with hepatitis C virus). Of the isolates of patients with and without cirrhosis, 174/464 (37.5%) and 1,783/4,041 (44.1%) were multiresistant, respectively (p = 0.007). E. coli was the most common multiresistant bacteria in both groups. Approximately 20% of E. coli and Klebsiella sp. isolates were ESBL-producers and 44% of S. aureus isolates were methicillin-resistant in cirrhotic patients. In cirrhotic patients admitted to the emergency department, hospital ward, and intensive care unit, 28.3%, 50% and 40% had multiresistant isolates, respectively. In patients with and without cirrhosis, 36.2% and 33.5% of isolates were resistant to third-generation cephalosporins, respectively. Conclusions: The empirical treatment of infections in hospitalized patients using broad-spectrum antibiotics should consider the observed pattern of bacterial resistance. PMID:27253738

  7. Gastric emptying time and the effect of cisapride in cirrhotic patients with autonomic neuropathy.

    Science.gov (United States)

    Gumurdulu, Yuksel; Yapar, Zeynep; Canataroglu, Abdullah; Serin, Ender; Gumurdulu, Derya; Kibar, Mustafa; Colakoglu, Salih

    2003-02-01

    GOALS To investigate the relationships between gastric emptying and autonomic dysfunction in hepatic cirrhosis and to assess the effects of cisapride on gastric emptying in cirrhotic patients. STUDY Twenty-four cirrhotic patients (8 patients in each Child-Pugh classification) and 25 healthy controls were enrolled. All the patients had viral (B or C) hepatitis. Patients with DM, alcoholic cirrhosis, active peptic ulcer, gastric malignancy and pyloric obstruction were excluded by esophagogastroduodenoscopy. Parasympathetic and sympathetic functions were assessed by the criteria set forth by Ewing and Clark. Drugs affecting GI motility and smoking were discontinued 48 hours and 12 hours prior to the study respectively. A solid-phase of gastric emptying study was conducted by scintigraphic method for the calculation of gastric half-emptying time (GET1/2). RESULTS The study revealed that 9 patients with Child-Pugh B and C cirrhosis had autonomic neuropathy and none of Child-Pugh A cirrhosis had autonomic neuropathy. Prolonged GET1/2 was noted in cirrhotics compared with the control group (p hepatitis may cause prolonged gastric emptying. Cisapride can shorten gastric emptying time in such patients. PMID:12544204

  8. Per rectal portal scintigraphy as a useful tool for predicting esophageal variceal bleeding in cirrhotic patients

    Institute of Scientific and Technical Information of China (English)

    Taned Chitapanarux; Ong-ard Praisontarangkul; Satawat Thongsawat; Pises Pisespongsa; Apinya Leerapun

    2007-01-01

    AIM: To investigate potential roles of per rectal portal scintigraphy in diagnosis of esophageal varices and predicting the risk of bleeding.METHODS: Fifteen normal subjects and fifty cirrhotic patients with endoscopically confirmed esophageal varices were included. Patients were categorized into bleeder and non-bleeder groups according to history of variceal bleeding. All had completed per rectal portal scintigraphy using 99mTechnetium pertechnetate.The shunt index was calculated from the ratio of 99mTechnetium pertechnetate in the heart and the liver.Data were analyzed using Student's t-test and receiver operating characteristics.RESULTS: Cirrhotic patients showed a higher shunt index than normal subjects (63.80 ± 25.21 vs 13.54 ± 6.46, P < 0.01). Patients with variceal bleeding showed a higher shunt index than those without bleeding (78.45 ± 9.40 vs 49.35 ± 27.72, P < 0.01). A shunt index of over 20% indicated the presence of varices and that of over 60% indicated the risk of variceal bleeding.CONCLUSION: In cirrhotic patients, per rectal portal scintigraphy is a clinically useful test for identifying esophageal varices and risk of variceal bleeding.

  9. Time-Dependent FTIR Spectral Changes in Rats of Massive Hemorrhage Death during the Later Postmortem Period

    Institute of Scientific and Technical Information of China (English)

    LI Shi-ying; SHAO Yu; LI Zheng-dong; LI Li; CHEN Yuan-yuan; CHEN Yi-jiu; HUANG Ping

    2012-01-01

    The aim of the current study was to investigate the spectra in the different organs of the rats which died of massive hemorrhage; to explore their spectral changes 15 days postmortem and the best mathematical model with different band absorption ratio changes to postmortem interval(PMD; and to compare the spectral changes of different temperature.Thirty male Sprague-Dawley rats were sacrificed by cutting abdominal aorta,and the cadavers were divided equally and kept at 4 ℃,20℃ and 30℃ in the control chamber.From the same rat,seven different organs were sampled at intervals of 1-15 days postmortem,and then measured by Fourier transfom infrared (FTIR) spectrometer.Six mathematical model functions were explored.The absorbance of bands and band absorbance ratios of absorption peak in each organ showed a time-dependent increase or decrease,most band absorbance ratios remaining stable for 7-15 days postmortem.Cubic model functions of the various bands absorbance ratios against PMI showed a stronger related coefficient.The absorbance bands with obvious changes at 20 ℃ showed stabilized tendencies at 4 ℃ and significant changes at 30 ℃ within 15 days postmortem.In addition,FTIR spectroscopy revealed a time-dependent metabolic process,with potential of being used to estimate PMI during 7 days postmortem,which merits further investigation.

  10. Early life inflammatory pain induces long-lasting deficits in hippocampal-dependent spatial memory in male and female rats.

    Science.gov (United States)

    Henderson, Yoko O; Victoria, Nicole C; Inoue, Kiyoshi; Murphy, Anne Z; Parent, Marise B

    2015-02-01

    The present experiment tested the hypothesis that neonatal injury disrupts adult hippocampal functioning and that normal aging or chronic stress during adulthood, which are known to have a negative impact on hippocampal function, exacerbate these effects. Male and female Sprague-Dawley rats were given an intraplantar injection of the inflammatory agent carrageenan (1%) on the day of birth and their memory was tested in the hippocampal-dependent spatial water maze in adulthood and again in middle age. We found that neonatal injury impaired hippocampal-dependent memory in adulthood, that the effects of injury on memory were more pronounced in middle-aged male rats, and that chronic stress accelerated the onset of these memory deficits. Neonatal injury also decreased glucocorticoid receptor mRNA in the dorsal CA1 area of middle-aged rats, a brain region critical for spatial memory. Morphine administration at the time of injury completely reversed injury-induced memory deficits, but neonatal morphine treatments in the absence of injury produced significant memory impairments in adulthood. Collectively, these findings are consistent with our hypothesis that neonatal injury produces long-lasting disruption in adult hippocampal functioning.

  11. The effect of pertussis toxin and whole-cell pertussis vaccine on haemodynamics and autonomic responsiveness in the rat depends on route of administration and age.

    Science.gov (United States)

    van Amsterdam, J G; te Biesebeek, J D; van de Kuil, T; van der Laan, J W; Wemer, J; de Wildt, D J; Vleeming, W

    1998-04-01

    Vaccination of children with Diphtheria, Tetanus, Poliomyelitis and pertussis vaccine (DTPoP-vaccine) containing the whole-cell pertussis component is known to be associated with manifestation of side-effects such as acute encephalopathy, convulsions and hypotensive-hyporesponsive episodes. In young and adult rats the effects of pertussis toxin and DTPoP-vaccine on haemodynamics and autonomic responsiveness are evaluated following treatment with high dose via different routes of administration (s.c., i.p. and i.v.). The effect of pertussis toxin is dose-dependent (between 1 and 20 micrograms kg-1) and largest responses are observed after i.v. administration. At 20 micrograms kg-1, i.v. pertussis toxin decreases baseline diastolic blood pressure and increases baseline heart rate by 31% and inhibits autonomic responsiveness (salbutamol-induced increase in diastolic blood pressure and arecoline-induced decrease in heart rate). In adult rats DTPoP-vaccine induces generally more prominent effects than in young rats. In adult rats DTPoP-vaccine reduces baseline diastolic blood pressure by 25% while no response is observed in young rats. In adult rats DTPoP inhibits the adrenergic response though less compared to treatment of pertussis toxin. After treatment with DTPoP-vaccine (single or twice) only minor differences are observed between young and adult rats. Present results show that adult rats are more sensitive to pertussis toxin and pertussis vaccine than young rats and that the responses depend on the route of administration.

  12. Long term sex-dependent psychoneuroendocrine effects of maternal deprivation and juvenile unpredictable stress in rats.

    Science.gov (United States)

    Llorente, R; Miguel-Blanco, C; Aisa, B; Lachize, S; Borcel, E; Meijer, O C; Ramirez, M J; De Kloet, E R; Viveros, M P

    2011-04-01

    We have analysed the long-term psychoneuroendocrine effects of maternal deprivation (MD) [24 h at postnatal day (PND) 9] and/or exposure to chronic unpredictable stress (CUS) during the periadolescent period (PND 28 to PND 43) in male and female Wistar rats. Animals were tested in the elevated plus maze (EPM, anxiety) at PND 44 and in two memory tests, spontaneous alternation and novel object recognition (NOT) in adulthood. The expression of hippocampal glucocorticoid (GR) and mineralocorticoid (MR) receptors, as well as of synaptophysin, neural cell adhesion molecule and brain-derived neurotrophic factor, was analysed by in situ hybridisation in selected hippocampal regions. Endocrine determinations of leptin, testosterone and oestradiol plasma levels were carried out by radioimmunoassay. Young CUS animals showed decreased anxiety behaviour in the EPM (increased percentage of time and entries in the open arms) irrespective of neonatal treatment. Memory impairments were induced by the two stressful treatments as was revealed by the NOT, with males being most clearly affected. Although each stressful procedure, when considered separately, induced different (always decrements) effects on the three synaptic molecules analysed and affected males and females differently, the combination of MD and CUS induced an unique disruptive effect on the three synaptic plasticity players. MD induced a long-term significant decrease in hippocampal GR only in males, whereas CUS tended to increase MR in males and decrease MR in females. Both neonatal MD and periadolescent CUS induced marked reductions in testosterone and oestradiol in males, whereas MD male animals also showed significantly decreased leptin levels. By contrast, in females, none of the hormones analysed was altered by any of the stressful procedures. Taking our data together in support of the 'two-hit' hypothesis, MD during neonatal life and/or exposure to CUS during the periadolescent period induced a permanent

  13. Risperidone regulates Dopamine D2-like receptors expression in rat brain in a time-dependent manner

    Directory of Open Access Journals (Sweden)

    Ni Peiyan

    2015-03-01

    Full Text Available Background and Objectives: Antipsychotics can elicit dopamine super-sensitivity by up-regulation of D2-like receptors (DRD2, DRD3, and DRD4 expression. Nevertheless, the expression profile of dopamine D2-like receptors in different brain regions and peripheral blood mononuclear cells (PBMCs, and changes following risperidone administration were still unclear. In this study, we would investigate the expression of D2-like receptors mRNA in different brain regions and the peripheral blood mononuclear cells (PBMCs in rats after 2, 6 weeks risperidone administration. Methods: The experimental rats were given risperidone (0.25mg/kg/day, i.p., and the control rats were given 0.9% NaCl. The rats were sacrificed at 0 week, 2 weeks and 6 weeks after the drug administration. Expression of the dopamine D2-like receptors was quantified by Real-time PCR method. Results: Dopamine D2-like receptors expressed in all the examined regions of rat brain. Their expression significantly increased 2weeks after risperidone administration in different brain regions. However, the changed expression of DRD2 and DRD3 turned back to the basal level 6weeks later, while the increased DRD4 expression remained in left parietal cortex. Meanwhile, DRD2 and DRD3 but not DRD4 expressed in PBMCs, however, the risperidone could not affect their expression. Conclusions: The risperidone could change the dopamine D2-like receptors expression in a time-dependent manner in different brain regions, which might guide the clinical use in the near future.

  14. Interleukin 1 dose-dependently affects the biosynthesis of (pro)insulin in isolated rat islets of Langerhans

    DEFF Research Database (Denmark)

    Spinas, G A; Hansen, B S; Linde, S;

    1987-01-01

    Human crude and recombinant interleukin 1 (IL-1) was found to dose- and time-dependently affect the biosynthesis of (pro)insulin in isolated rat islets of Langerhans. Incubation of rat islets with either 0.5 U/ml or 5 U/ml of crude IL-1 for 1 h had no detectable effect on (pro)insulin biosynthesis....... After 24 hours of exposure 0.5 U/ml of crude or 0.6 ng/ml of recombinant IL-1 (beta) increased the (pro)insulin biosynthesis by 42% and 58%, respectively, whereas a 10-fold greater concentration of IL-1 decreased the (pro)insulin biosynthesis by 74% and 89%, respectively. The increase in (pro...

  15. Effect of 15% Alcohol Dependence on Alveolar Bone Loss and TNF-α Secretion in Wistar Rats.

    Science.gov (United States)

    Wagner, Marcius Comparsi; Rocha, José Mariano da; Gaio, Eduardo José; Cavagni, Juliano; Carrard, Vinícius Coelho; Rösing, Cassiano Kuchenbecker

    2016-01-01

    The aim of the present study was to evaluate the effect of 15% alcohol dependence on ligature-induced alveolar bone loss and TNF-α secretion in Wistar rats. Thirty-three male Wistar rats aged 45-60 days (mean weight=253 g) were randomly allocated test or control groups. Test group (n=18) received 15% alcohol as liquid intake and control group (n=15) received water during the experimental period. TNF-α was analyzed by ELISA assay in 11 animals per group. After 14 days of alcohol/water intake, alcohol dependency was assessed and silk ligatures were placed around the left second upper molars. Ligature presence and body weight were checked weekly. After 40 days, animals were sacrificed and the maxillae were defleshed for morphometric analysis using standardized images. All animals in the test group displayed signs of alcohol dependency at day 14. No statistically significant differences in final body weight (334.83±21.38 vs. 322.48±30.65 g, p=0.20) were observed between groups. In relation to alveolar bone loss, no statistically significant difference was observed among test and control groups both for ligated teeth (0.76±0.06 vs. 0.74±0.10 mm, p=0.60) and unligated teeth (0.41±0.16 vs. 0.35±0.05 mm, p=0.22). The TNF-α secretion also did not display statistically significant differences between test and control groups (10.78±1.84 vs. 12.13±2.11 pg/mL, p=0.12). It may be concluded that 15% alcohol dependency was not capable to alter alveolar bone loss and TNF-α secretion in Wistar rats.

  16. Hydrogen sulfide inhibits L-type calcium currents depending upon the protein sulfhydryl state in rat cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Rongyuan Zhang

    Full Text Available Hydrogen sulfide (H(2S is a novel gasotransmitter that inhibits L-type calcium currents (I (Ca, L. However, the underlying molecular mechanisms are unclear. In particular, the targeting site in the L-type calcium channel where H(2S functions remains unknown. The study was designed to investigate if the sulfhydryl group could be the possible targeting site in the L-type calcium channel in rat cardiomyocytes. Cardiac function was measured in isolated perfused rat hearts. The L-type calcium currents were recorded by using a whole cell voltage clamp technique on the isolated cardiomyocytes. The L-type calcium channel containing free sulfhydryl groups in H9C2 cells were measured by using Western blot. The results showed that sodium hydrosulfide (NaHS, an H(2S donor produced a negative inotropic effect on cardiac function, which could be partly inhibited by the oxidant sulfhydryl modifier diamide (DM. H(2S donor inhibited the peak amplitude of I( Ca, L in a concentration-dependent manner. However, dithiothreitol (DTT, a reducing sulfhydryl modifier markedly reversed the H(2S donor-induced inhibition of I (Ca, L in cardiomyocytes. In contrast, in the presence of DM, H(2S donor could not alter cardiac function and L type calcium currents. After the isolated rat heart or the cardiomyocytes were treated with DTT, NaHS could markedly alter cardiac function and L-type calcium currents in cardiomyocytes. Furthermore, NaHS could decrease the functional free sulfhydryl group in the L-type Ca(2+ channel, which could be reversed by thiol reductant, either DTT or reduced glutathione. Therefore, our results suggest that H(2S might inhibit L-type calcium currents depending on the sulfhydryl group in rat cardiomyocytes.

  17. Dose-dependent effect of N'-Nitrosodiethylamine on hepatic architecture, RBC rheology and polypeptide repertoire in Wistar rats

    Science.gov (United States)

    Mukherjee, Devoshree

    2015-01-01

    N'-Nitrosodiethylamine (NDEA) is an effective hepatotoxicant, carcinogen and mutagen. NDEA-induced hepatic necrosis, through metabolic activation by CYP2E1, is an extensively used experimental model. In the present study, we analysed the dose- and time-dependent effect of NDEA on hepatic damage, RBC rheology and proteomic profile in male Wistar rats. The rats, 5–6 weeks old, were divided into four groups: Group-1 served as control and received normal saline, Group-2 received a single dose of 200 mg/kg body weight NDEA intraperitoneally (i.p.) and the animals were sacrificed after one week; the rats of Group-3 received a single dose of 100 mg/kg body weight NDEA and were sacrificed after one week; Group-4 received 100 mg/kg body weight/wk NDEA for two weeks and were then sacrificed. Various biochemical parameters such as ALT, AST, ALP and bilirubin were determined. Further, RBC rheology, histopathology (H&E staining) of liver biopsies and polypeptide profiling (SDS-PAGE) in sera and liver sections were also carried out both in control and NDEA treated groups. Our results showed a significant increase in all the biochemical parameters of the liver function test (prat sera and liver revealed qualitative and quantitative differences in polypeptide composition. Based on the presence/absence, polypeptides were classified in three different categories: (1) house-keeping, present in all the groups investigated; (2) novel, present in either control or NDEA treated group at any given time; (3) differential expression, showing quantitative differences. Our study indicates a dose and time-dependent hepatocellular damage and proteome profile which is likely due to NDEA-mediated oxidative stress in rats.

  18. Agmatine induced NO dependent rat mesenteric artery relaxation and its impairment in salt-sensitive hypertension.

    Science.gov (United States)

    Gadkari, Tushar V; Cortes, Natalie; Madrasi, Kumpal; Tsoukias, Nikolaos M; Joshi, Mahesh S

    2013-11-30

    l-Arginine and its decarboxylated product, agmatine are important mediators of NO production and vascular relaxation. However, the underlying mechanisms of their action are not understood. We have investigated the role of arginine and agmatine in resistance vessel relaxation of Sprague-Dawley (SD) and Dahl salt-sensitive hypertensive rats. Second or 3rd-order mesenteric arterioles were cannulated in an organ chamber, pressurized and equilibrated before perfusing intraluminally with agonists. The vessel diameters were measured after mounting on the stage of a microscope fitted with a video camera. The gene expression in Dahl rat vessel homogenates was ascertained by real-time PCR. l-Arginine initiated relaxations (EC50, 5.8±0.7mM; n=9) were inhibited by arginine decarboxylase (ADC) inhibitor, difluoromethylarginine (DFMA) (EC50, 18.3±1.3mM; n=5) suggesting that arginine-induced vessel relaxation was mediated by agmatine formation. Agmatine relaxed the SD rat vessels at significantly lower concentrations (EC50, 138.7±12.1μM; n=22), which was compromised by l-NAME (l-N(G)-nitroarginine methyl ester, an eNOS inhibitor), RX821002 (α-2 AR antagonist) and pertussis toxin (G-protein inhibitor). The agmatine-mediated vessel relaxation from high salt Dahl rats was abolished as compared to that from normal salt rats (EC50, 143.9±23.4μM; n=5). The α-2A AR, α-2B AR and eNOS mRNA expression was downregulated in mesenteric arterioles of high-salt treated Dahl hypertensive rats. These findings demonstrate that agmatine facilitated the relaxation via activation of α-2 adrenergic G-protein coupled receptor and NO synthesis, and this pathway is compromised in salt-sensitive hypertension.

  19. Weight/age-dependent glucose turnover (GTO) in fed and 24 hour fasted rats

    International Nuclear Information System (INIS)

    In small animals such as the rat, cardiac output and oxygen consumption are constant with age when normalized to the body surface area but not to body weight (BW). The authors explored this relationship for GTO in pentobarbital-anesthetized fed and 24 hours fasted Sprague-Dawley rats weighing between 200 and 55 g. A bolus of 10 μCi/kg BW of [6-3H]-glucose was injected into the carotid artery followed by a constant infusion equal to 1.5 μCi/minute *kg BW and samples taken from the right atrium every 15 minutes for glucose specific activity (SA) measurements over a 2 period. Steady state measurements of GTO (μmol/minute) plotted as a function of BW (g) revealed GTO to be inversely related in fed rats but independent of BW in fasted rats. Although plasma [glucose] was significantly lower in fasted rats, there were no weight related differences within each group. Fasting decreased GTO across the whole range of body weights; however, the magnitude of the fasting effect was much larger in the smaller animals (50% lower) compared to the larger animals (25% lower). Although the lean body mass is increasing in this range of BW, the decrease in GTO indicates an age/weight-related decrease in glucose utilization which diminishes the effect of fasting as the animal grows. This data explains the inconsistency in the literature regarding the fasting effect on GTO in the rat and emphasizes the importance of weight/age matching of experimental groups to minimize the variability in the data when GTO is of interest

  20. Aging-Dependent Regulation of Antioxidant Enzymes and Redox Status in Chronically Loaded Rat Dorsiflexor Muscles

    OpenAIRE

    Ryan, Michael J.; Dudash, Holly J.; Docherty, Megan; Geronilla, Kenneth B.; Baker, Brent A.; Haff, G. Gregory; Cutlip, Robert G; Alway, Stephen E.

    2008-01-01

    This study compares changes in the pro-oxidant production and buffering capacity in young and aged skeletal muscle after exposure to chronic repetitive loading (RL). The dorsiflexors from one limb of young and aged rats were loaded 3 times/week for 4.5 weeks using 80 maximal stretch-shortening contractions per session. RL increased H2O2 in tibialis anterior muscles of young and aged rats and decreased the ratio of reduced/oxidized glutathione and lipid peroxidation in aged but not young adult...

  1. Extensive Sex- and/or Hormone-Dependent Expression of Rat Housekeeping Genes

    OpenAIRE

    Das, Rajat K.; Banerjee, Sarmistha; Shapiro, Bernard H.

    2012-01-01

    Using a commercially available qRT-PCR array designed to measure the expression of 32 rat housekeeping genes, we found that the levels of 5 of the genes were sexually dimorphic, 22 genes were over-expressed and one under-expressed in multi-hormone deficient hypophysectomized rats of both sexes. Only 3 genes fulfilled the stability criteria determined by geNorm and NormFinder as suitable housekeeping genes. Normalizing qRT-PCR data with either of these 3 genes alone, the geometric means of any...

  2. Vigorous, but differential mononuclear cell response of cirrhotic patients to bacterial ligands

    Institute of Scientific and Technical Information of China (English)

    Varenka J Barbero-Becerra; María Concepción Gutiérrez-Ruiz; Carmen Maldonado-Bernal; Félix I Téllez-Avila; Roberto Alfaro-Lara; Florencia Vargas-Vorácková

    2011-01-01

    AIM: To study the role of gram-positive and gram-negative bacteria in the pathogenesis of liver injury, specifically the activation of inflammatory mediators. METHODS: Peripheral blood mononuclear cells of 20 out-patients were studied, 10 of them with cirrhosis. Peripheral blood mononuclear cells were isolated and exposed to lipopolysaccharide or lipoteichoic acid. CD14, Toll-like receptor 2 and 4 expression was determined by flow cytometry, and tumor necrosis factor (TNF) α, interleukin (IL)-1β, IL-6, IL-12 and IL-10 secretion in supernatants was determined by ELISA. RESULTS: Higher CD14, Toll-like receptor 2 and 4 expression was observed in peripheral blood mononuclear cells from cirrhotic patients, (P < 0.01, P < 0.006, P < 0.111) respectively. Lipopolysaccharide and lipoteichoic acid induced a further increase in CD14 expression (P < 0.111 lipopolysaccharide, P < 0.013 lipoteichoic acid), and a decrease in Toll-like receptor 2 (P < 0.008 lipopolysaccharide, P < 0.008 lipoteichoic acid) and Toll-like receptor 4 (P < 0.008 lipopolysaccharide, P < 0.028 lipoteichoic acid) expression. With the exception of TNFα, absolute cytokine secretion of peripheral blood mononuclear cells was lower in cirrhotic patients under nonexposure conditions (P < 0.070 IL-6, P < 0.009 IL-1β, P < 0.022 IL-12). Once exposed to lipopolysaccharide or lipoteichoic acid, absolute cytokine secretion of peripheral blood mononuclear cells was similar in cirrhotic and non-cirrhotic patients, determining a more vigorous response in the former (P < 0.005 TNFα, IL-1β, IL-6, IL-2 and IL-10 lipopolysaccharide; P < 0.037 TNFα; P < 0.006 IL-1β; P < 0.005 IL-6; P < 0.007 IL-12; P < 0.014 IL-10 lipoteichoic acid). Response of peripheral blood mononuclear cells was more intense after lipopolysaccharide than after lipoteichoic acid exposure. CONCLUSION: Peripheral blood mononuclear cells of cirrhotic patients are able to respond to a sudden bacterial ligand exposure, particularly lipopolysaccharide

  3. Dose-dependent effect of N′-Nitrosodiethylamine on hepatic architecture, RBC rheology and polypeptide repertoire in Wistar rats

    Directory of Open Access Journals (Sweden)

    Mukherjee Devoshree

    2015-03-01

    Full Text Available N′-Nitrosodiethylamine (NDEA is an effective hepatotoxicant, carcinogen and mutagen. NDEA-induced hepatic necrosis, through metabolic activation by CYP2E1, is an extensively used experimental model. In the present study, we analysed the dose- and time-dependent effect of NDEA on hepatic damage, RBC rheology and proteomic profile in male Wistar rats. The rats, 5–6 weeks old, were divided into four groups: Group-1 served as control and received normal saline, Group-2 received a single dose of 200 mg/kg body weight NDEA intraperitoneally (i.p. and the animals were sacrificed after one week; the rats of Group-3 received a single dose of 100 mg/kg body weight NDEA and were sacrificed after one week; Group-4 received 100 mg/kg body weight/wk NDEA for two weeks and were then sacrificed. Various biochemical parameters such as ALT, AST, ALP and bilirubin were determined. Further, RBC rheology, histopathology (H&E staining of liver biopsies and polypeptide profiling (SDS-PAGE in sera and liver sections were also carried out both in control and NDEA treated groups. Our results showed a significant increase in all the biochemical parameters of the liver function test (p<0.05. In NDEA treated categories dacryocytes (tear drop cells, schistocytes (fragmented cells, codocytes (target cells, acanthocytes (spur cells and ovalocytes (oval cells were observed. H & E stained liver biopsies treated with NDEA showed abnormal liver architecture with severe haemorrhage, neutrophilic infiltration and dysplastic hepatocytes manifested in a dose-dependent manner. Software analysis of SDS-PAGE of control and NDEA treated rat sera and liver revealed qualitative and quantitative differences in polypeptide composition. Based on the presence/absence, polypeptides were classified in three different categories: (1 house-keeping, present in all the groups investigated; (2 novel, present in either control or NDEA treated group at any given time; (3 differential expression

  4. Age-dependent effects of conditioning on cholinergic and vasopressin systems in the rat suprachiasmatic nucleus

    NARCIS (Netherlands)

    Biemans, BAM; Van der Zee, EA; Daan, S

    2003-01-01

    Active shock avoidance was used to explore the impact of behavioural stimulation on the neurochemistry of the suprachiasmatic nucleus. We have found previously that the expression of muscarinic acetylcholine receptors in the suprachiasmatic nucleus of young rats was significantly enhanced 24 hours a

  5. Ethyl benzene-induced ototoxicity in rats : a dose-dependent mild-frequency hearing loss

    NARCIS (Netherlands)

    Cappaert, N.L.M.; Klis, S.F.L.; Baretta, A.B.; Muijser, H.; Smoorenburg, G.F.

    2000-01-01

    Rats were exposed to ethyl benzene at 0, 300, 400 and 550 ppm for 8 hours/day for 5 consecutive days. Three to six weeks after the exposure, auditory function was tested by measuring compound action potentials (CAP) in the frequency range of 1-24 kHz and 2f1-f2 distortion product otoacoustic emissio

  6. Age dependent accumulation of N-acyl-ethanolamine phospholipids in ischemic rat brain

    DEFF Research Database (Denmark)

    Moesgaard, B.; Petersen, G.; Hansen, Harald S.;

    2000-01-01

    N-acyl-ethanolamine phospholipids (NAPE) can be formed as a stress response during neuronal injury, and they are precursors for N-acyl- ethanolamines (NAE), some of which are endocannabinoids. The levels of NAPE accumulated during post-decapitative ischemia (6 h at 37°C) were studied in rat brains...... of various age (1, 6, 12, 19, 30, and ~70 days) by the use of P NMR spectroscopy of lipid extracts. This ability to accumulate NAPE was compared with the activity of N-acyltransferase and of NAPE-hydrolyzing phospholipase D (NAPE-PLD) in brain microsomes. These two enzymes are involved in the formation...... and degradation of NAPE, respectively. The results showed that 1) the ability to accumulate NAPE during post-decapitative ischemia is especially high in the youngest rats and is markedly reduced in older brains [in 1-day-old rat brains NAPE accumulated to 1.5% of total phospholipids, while in 30-day-old rat...

  7. Microsomal quercetin glucuronidation in rat small intestine depends on age and segment

    Science.gov (United States)

    UDP-glucuronosyltransferase (UGT) activity toward the flavonoid quercetin and UGT protein were characterized in 3 equidistant small intestine (SI) segments from 4, 12, 18, and 28 mo male F344 rats, n=8/age using villin to control for enterocyte content. SI microsomal intrinsic clearance of quercetin...

  8. AUTIFERTILITY EFFECT OF METHOXYCHLOR IN FEMALE RATS: DOSE AND TIME DEPENDENT BLOCKADE OF PREGNANCY

    Science.gov (United States)

    Long-term exposure to methoxychlor (MXC) an estrogenic pesticide, produces infertility in rats, and short-term exposure blocks the decidual cell response (DCR). To address the short-term effects of MXC on fertility, the differential effects of MXC dosage and timing of administrat...

  9. Evidence for novel age-dependent network structures as a putative primo vascular network in the dura mater of the rat brain.

    Science.gov (United States)

    Lee, Ho-Sung; Kang, Dai-In; Yoon, Seung Zhoo; Ryu, Yeon Hee; Lee, Inhyung; Kim, Hoon-Gi; Lee, Byung-Cheon; Lee, Ki Bog

    2015-07-01

    With chromium-hematoxylin staining, we found evidence for the existence of novel age-dependent network structures in the dura mater of rat brains. Under stereomicroscopy, we noticed that chromium-hematoxylin-stained threadlike structures, which were barely observable in 1-week-old rats, were networked in specific areas of the brain, for example, the lateral lobes and the cerebella, in 4-week-old rats. In 7-week-old rats, those structures were found to have become larger and better networked. With phase contrast microscopy, we found that in 1-week-old rats, chromium-hematoxylin-stained granules were scattered in the same areas of the brain in which the network structures would later be observed in the 4- and 7-week-old rats. Such age-dependent network structures were examined by using optical and transmission electron microscopy, and the following results were obtained. The scattered granules fused into networks with increasing age. Cross-sections of the age-dependent network structures demonstrated heavily-stained basophilic substructures. Transmission electron microscopy revealed the basophilic substructures to be clusters with high electron densities consisting of nanosized particles. We report these data as evidence for the existence of age-dependent network structures in the dura mater, we discuss their putative functions of age-dependent network structures beyond the general concept of the dura mater as a supporting matrix. PMID:26330833

  10. Evidence for novel age-dependent network structures as a putative primo vascular network in the dura mater of the rat brain

    Directory of Open Access Journals (Sweden)

    Ho-Sung Lee

    2015-01-01

    Full Text Available With chromium-hematoxylin staining, we found evidence for the existence of novel age-dependent network structures in the dura mater of rat brains. Under stereomicroscopy, we noticed that chromium-hematoxylin-stained threadlike structures, which were barely observable in 1-week-old rats, were networked in specific areas of the brain, for example, the lateral lobes and the cerebella, in 4-week-old rats. In 7-week-old rats, those structures were found to have become larger and better networked. With phase contrast microscopy, we found that in 1-week-old rats, chromium-hematoxylin-stained granules were scattered in the same areas of the brain in which the network structures would later be observed in the 4- and 7-week-old rats. Such age-dependent network structures were examined by using optical and transmission electron microscopy, and the following results were obtained. The scattered granules fused into networks with increasing age. Cross-sections of the age-dependent network structures demonstrated heavily-stained basophilic substructures. Transmission electron microscopy revealed the basophilic substructures to be clusters with high electron densities consisting of nanosized particles. We report these data as evidence for the existence of age-dependent network structures in the dura mater, we discuss their putative functions of age-dependent network structures beyond the general concept of the dura mater as a supporting matrix.

  11. Effects of voluntary exercise on anxiety-like behavior and voluntary morphine consumption in rat pups borne from morphine-dependent mothers during pregnancy.

    Science.gov (United States)

    Haydari, Sakineh; Miladi-Gorji, Hossein; Mokhtari, Amin; Safari, Manouchehr

    2014-08-22

    Exposure to morphine during pregnancy produced long-term effects in offspring behaviors. Recent studies have shown that voluntary exercise decreases the severity of anxiety behaviors in both morphine-dependent and withdrawn rats. Thus, the aims of the present study were to examine whether maternal exercise decreases prenatal dependence-induced anxiety and also, voluntary consumption of morphine in animal models of craving in rat pups. Pregnant rats were made dependent by chronic administration of morphine in drinking water simultaneously with access to a running wheel that lasted at least 21 days. Then, anxiety-like behaviors using the elevated plus-maze (EPM) and voluntary consumption of morphine using a two-bottle choice paradigm (TBC) were tested in male rat pups. The results showed that the rat pups borne from exercising morphine-dependent mothers exhibited an increase in EPM open arm time (Pexercising morphine-dependent mothers was less in the second (Pexercise decreases the severity of the anxiogenic-like behaviors and voluntary consumption of morphine in rat pups.

  12. Antidepressant-like properties of phosphodiesterase type 5 inhibitors and cholinergic dependency in a genetic rat model of depression.

    Science.gov (United States)

    Liebenberg, Nico; Harvey, Brian H; Brand, Linda; Brink, Christiaan B

    2010-09-01

    We explored the antidepressant-like properties of two phosphodiesterase type 5 (PDE5) inhibitors in a genetic animal model of depression, namely Flinders sensitive line rats. We investigated the dose-dependency of the antidepressant-like action of sildenafil, and its interaction with the cholinergic system and behavioural correlates of monoaminergic neurotransmission, in the forced swim test. Antidepressant-like properties of tadalafil (a structurally distinct PDE5 inhibitor) were also evaluated. Flinders sensitive line rats were treated for 14 days with vehicle, fluoxetine, atropine or PDE5 inhibitors+/-atropine. Immobility, swimming and climbing behaviours were assessed in the forced swim test. In combination with atropine (1 mg/kg), both sildenafil (10, 20 mg/kg) and tadalafil (10 mg/kg) decreased immobility while increasing swimming (serotonergic) and climbing (noradrenergic) behaviours. Interestingly, sildenafil (3 mg/kg) decreased immobility while selectively increasing climbing behaviour in the absence of atropine. These results suggest that the antidepressant-like activity of PDE5 inhibitors involve alterations in monoaminergic neurotransmission, but involve a dependence on inherent cholinergic tone so that the final response is determined by the relative extent of activation of these systems. Furthermore, the behavioural profile of sildenafil alone, and its observed antidepressant-like properties, shows strict dose-dependency, with only higher doses showing an interaction with the cholinergic system.

  13. Analysis of Age Dependent Effects of Heat Stress on EEG Frequency Components in Rats

    Institute of Scientific and Technical Information of China (English)

    RAKESH KUMAR SINHA

    2009-01-01

    Objective To demonstrate changes in different frequencies of cerebral electrical activity or electroencephalogram (EEG) following exposure to high environmental heat in three different age groups of freely moving rats. Methods Rats were divided into three groups (i) acute heat stress - subjected to a single exposure for four hours at 38 ℃; (ii) chronic heat stress -exposed for 21 days daily for one hour at 38 ℃, and (iii) handling control groups. The digital polygraphic sleep-EEG recordings were performed just after the heat exposure from acute stressed rats and on 22nd day from chronic stressed rats by simultaneous recording of cortical EEG EOG (electrooculogram), and EMG (electromyogram). Further, power spectrum analyses were performed to analyze the effects of heat stress. Results The frequency analysis of EEG signals following exposure to high environmental heat revealed that in all three age groups of rats, changes in higher frequency components (β2) were significant in all sleep-wake states following both acute and chronic heat stress conditions. After exposure to acute heat, significant changes in EEG frequencies with respect to their control groups were observed, which were reversed partly or fully in four hours of EEG recording. On the other hand, due to repetitive chronic exposure to hot environment, adaptive and long-term changes in EEG frequency patterns were observed. Conclusion The present study has exhibited that the cortical EEG is sensitive to environmental heat and alterations in EEG frequencies in different sleep-wake states due to heat stress can be differentiated efficiently by EEG power spectrum analysis.

  14. Dose-dependent effects, safety and tolerability of fenugreek in diet-induced metabolic disorders in rats

    OpenAIRE

    Muraki Etsuko; Hayashi Yukie; Chiba Hiroshige; Tsunoda Nobuyo; Kasono Keizo

    2011-01-01

    Abstract Background We previously reported that fenugreek (Trigonella foenum-graecum L.) improved diet-induced metabolic disorders in rats. The purpose of the present study was to examine the dose-dependent effects, safety and tolerability of fenugreek. Methods The diets used in this study were the high-fat high-sucrose diet (HFS; lard 50%kcal, sucrose 25%kcal) as a control (Ctrl group) or the HFS containing 0.25% (VL group), 1.25% (L group), 2.50% (M group), 5.00% (H group) or 12.30% (VH gro...

  15. Activity of interferon-dependent 2',5'-oligoadenylate synthetase in rat lymphoid cells under transformed environment conditions

    Science.gov (United States)

    Ostapchenko, L. I.; Mikhailik, I. V.; Prokopova, K. V.

    It is detected that interferon-dependent 2',5'-oligoadenylate synthetase is a sensitive index of immunocompetent cells functional state under transformed environment conditions. Microgravitation and ionising radiation induce increase of investigated enzyme activity in rat lymphocytes, which can be a result of lymphoid cells compensatory mechanisms starting in response to stress factors action. Administration of interferon inductors permits to stimulate the 2',5'-oligoadenylate synthetase, which enables one to correct pathological changes in the cells and to intensify adaptive reactions of immune systems.

  16. Age-dependent decline in learning and memory performances of WAG/Rij rat model of absence epilepsy

    OpenAIRE

    Karson Ayşe; Utkan Tijen; Balcı Fuat; Arıcıoğlu Feyza; Ateş Nurbay

    2012-01-01

    RESEARCH Open Access Age-dependent decline in learning and memory performances of WAG/Rij rat model of absence epilepsy Ayşe Karson1*, Tijen Utkan2, Fuat Balcı3, Feyza Arıcıoğlu4 and Nurbay Ateş1 Abstract Recent clinical studies revealed emotional and cognitive impairments associated with absence epilepsy. Preclinical research with genetic models of absence epilepsy however have primarily focused on dysfunctional emotional processes and paid relatively less attention t...

  17. Effect of H pylori infection and its eradication on hyperammo-nemia and hepatic encephalopathy in cirrhotic patients

    Institute of Scientific and Technical Information of China (English)

    Shu-Jie Chen; Liang-Jing Wang; Qin Zhu; Jian-Ting Cai; Tao Chen; Jian-Min Si

    2008-01-01

    AIM: To investigate the relationship between H pylori infection, blood ammonia concentration and hepatic encephalopathy (HE), and the effect of H pylori eradication in cirrhotic patients.METHODS: From July 2003 to January 2005, 457 cirrhotic patients in five regions of Zhejiang Province were enrolled. Patients were evaluated for demographics, number connection test, H pylori infection, liver impairment, blood ammonia concentration and HE. Patients with H pylori infection were given 1 wk therapy with omeprazole plus clarithromycin and tinidazole. 14C urea breath test was performed and mental symptoms and blood ammonia level were reassessed after bacterium eradication.RESULTS: Overall H pylori infection rate was 60.6%, and HE occurred in 47.5% of cirrhotic patients. Subclinical HE (SHE) was detected in 55 of 117 cirrhotic patients. Blood ammonia concentration in H pylori negative (n = 180) and positive (n = 277) cirrhotic patients was 53.8 ± 51.4 and 78.4 ± 63.6 nmol/L, respectively (P < 0.01), which was significantly reduced to 53.5 ± 37.7 nmol/L after bacterium eradication (n = 126) (P < 0.01). Blood ammonia was 97.5 ± 81.0 nmol/L in H py/ori-positive cirrhotic patients, and this did not significantly change in those with persistent infection after H pylori eradication (n = 11). HE was more frequently observed in patients with H pylori infection than in those without (58.5% vs 30.6%, P < 0.01). HE rate significantly dropped to 34.1% after H pylori eradiation (P < 0.01). H pylori prevalence significantly differed among cirrhotic patients with HE (74.4%), SHE (69.1%), and those without HE (53.2%) (P < 0.05). Blood ammonia level was significantly different among cirrhotic patients with HE (94.5 ± 75.6 nmol/L), SHE (59.9 ± 49.2 nmol/L), and without HE (47.3 ± 33.5 nmol/L) (P < 0.05). Logistic regression analysis showed that blood ammonia concentration, Child-Pugh stage, upper gastrointestinal bleeding, electrolyte disturbance, and urea nitrogen were risk factors

  18. Perch size and structure have species-dependent effects on the arboreal locomotion of rat snakes and boa constrictors.

    Science.gov (United States)

    Jayne, Bruce C; Herrmann, Michael P

    2011-07-01

    Arboreal habitats create diverse challenges for animal locomotion, but the numerical and phylogenetic diversity of snakes that climb trees suggest that their overall body plan is well suited for this task. Snakes have considerable diversity of axial anatomy, but the functional consequences of this diversity for arboreal locomotion are poorly understood because of the lack of comparative data. We simulated diverse arboreal surfaces to test whether environmental structure had different effects on the locomotion of snakes belonging to two distantly related species with differences in axial musculature and stoutness. On most cylindrical surfaces lacking pegs, both species used concertina locomotion, which always involved periodic stopping and gripping but was kinematically distinct in the two species. On horizontal cylinders that were a small fraction of body diameter, the boa constrictors used a balancing form of lateral undulation that was not observed for rat snakes. For all snakes the presence of pegs elicited lateral undulation and enhanced speed. For both species maximal speeds decreased with increased incline and were greatest on cylinders with intermediate diameters that approximated the diameter of the snakes. The frictional resistances that we studied had small effects compared with those of cylinder diameter, incline and the presence of pegs. The stouter and more muscular boa constrictors were usually faster than the rat snakes when using the gripping gait, whereas rat snakes were faster when using lateral undulation on the surfaces with pegs. Thus, variation in environmental structure had several highly significant effects on locomotor mode, performance and kinematics that were species dependent.

  19. Antihyperglycemic and antioxidant effects of Talinum portulacifolium leaf extracts in streptozotocin diabetic rats: A dose-dependent study

    Directory of Open Access Journals (Sweden)

    Ramesh K Babu

    2009-01-01

    Full Text Available Hexane, ethanolic and aqueous extracts of Talinum portulacifolium leaves were prepared and given individually at different doses to normal and streptozotocin (STZ induced diabetic rats after an overnight fast. The blood glucose levels were measured at 0,1,2,3,4,5 and 6 h after the treatment. The hexane extract at a dosage of 0.5g/kg b.w has shown maximal blood glucose lowering effect (64.7% in diabetes rats. The same dosage did not produce any hypoglycemic activity in normal rats. The antihyperglycemic activity of hexane extract of Talinum portulacifolium leaves was significantly higher than that of glibenclamide, an oral hypoglycemic agent. All the extracts exhibited dose dependent scavenging activities against 2,2-diphenly-1-picrylhydrazyl (DPPH radicals, nitric oxide radicals and hydrogen peroxide. Further, all extracts had relatively lower reducing power, compared to that of ascorbic acid. The total phenolic content of hexane, ethanol and aqueous extracts were found to be 61, 100 and 114 mg/gm of the dry extract respectively. TLC of the above extracts using the DPPH as a spraying reagent revealed yellow spots against purple background indicating the presence of potent antioxidant compounds. In conclusion hexane extract of Talinum portulacifolium leaves possess both antihyperglycemic and antioxidant activites, while the ethanol and aqueous extracts possess only antioxidant activity.

  20. The metabolism and binding properties of 3H-aldosterone in plasma and its sex dependence in adrenalectomized rats.

    Science.gov (United States)

    Morris, D J; Graham, W C; Davis, R P

    1975-01-01

    The rates of clearance of plasma 3-H radioactivitivity following intravenous injection of 3-H aldosterone was demonstrated to be sex-dependent in adrenalectomized rats. The perchantage plasma radioactivity which is CH-2CL-2extractable is greater in female than in male rats from 5 min to 90 min postinjection; however the quantities of CH2-CL2-extractable label are not significantly different until 60 min postinjection. The quantities of nonextractable, water-soluble metabolites of adosterone (NEPD), which are markedly greater in the plasma of males, reach peak levels 30 min after injections of aldosterone, during the latent period of the hormone.N females, these polar metabolites (NEPD)are rapidly cleared from the blood. The quantities of 3-H-radioactivity associated with the plasma binding proteins are similar in both males and females. The unbound levels of aldosterone and its metabolities are significantly greater in the plasma of males. These findings indicate that the sex hormones may influence not only the metabolism of aldosterone in rats, but also the plasma levels of unmetabolized aldosterone and its metabolites. PMID:1109901

  1. Trabecular bone response to mechanical loading in ovariectomized Sprague-Dawley rats depends on baseline bone quantity.

    Science.gov (United States)

    Ko, Chang-Yong; Jung, Young Jin; Park, Ji Hyung; Seo, Donghyun; Han, Paul; Bae, Kiho; Schreiber, Jürgen; Kim, Han Sung

    2012-07-26

    Mechanical loading is one of the determining factors for bone modulation, and is therefore frequently used to treat or prevent bone loss; however, there appears to be no data on the effects of baseline bone quantity on this response. This study aimed to verify whether baseline bone quantity affects osteoporotic trabecular bone adaptive response to mechanical stimulation. Twenty-four female Sprague-Dawley (SD) rats were ovariectomized (OVX). After 3 weeks of OVX, rats were divided into a high bone quantity and a low bone quantity group, and rats in each group were then subdivided into 4 groups that were exposed to different loading strategies. In the loading groups, tibiae were stimulated through axial loading at 2000με of strain, for 1500 cycles each of 75s, 150s, or 250s. The sham treatment groups received no loading. Changes in BV/TV for trabecular bone in the tibia were measured at the baseline (before loading), and at 3 weeks and 6 weeks after loading. BV/TVs in loading groups of the low baseline bone quantity group were significantly increased at 6 weeks, compared with those in the no-loading groups (p0.05). A significant negative correlation was observed between baseline BV/TV and its relative variations at 3 weeks or 6 weeks (p<0.05). These results indicate that adaptive responses of osteoporotic trabecular bone to mechanical loading depend on baseline bone quantity. PMID:22663762

  2. Strain-dependent differences in sensitivity of rat beta-cells to interleukin 1 beta in vitro and in vivo

    DEFF Research Database (Denmark)

    Reimers, J I; Andersen, H U; Mauricio, D;

    1996-01-01

    The aim of this study was to investigate whether strain-dependent differences in beta-cell sensitivity to interleukin (IL) 1 beta exist in vitro and in vivo and if so, whether these differences correlate to variations in IL-1 beta-induced islet inducible nitric oxide synthase (iNOS) mRNA expression....../CR) rats were resistant. Furthermore, IL-1 beta induced higher islet iNOS mRNA expression and nitric oxide production from WK/Mol islets compared with BN/CR islets. WK/Mol, WK/CR, BN/Mol, BN/CR, and Lewis-Scripps/Mol (LS/Mol) rats received one daily injection of recombinant human IL-1 beta (4.0 microg...... and nitrite production in vitro and islet iNOS protein content in vivo. Isolated islets of Langerhans in vitro from Wistar-Kyoto/Møllegården (WK/Mol) rats were sensitive to the inhibitory effect of IL-1 beta on accumulated and acute insulin secretion, whereas islets from Brown Norway/Charles River (BN...

  3. Single photon emission computed tomography and statistical parametric mapping analysis in cirrhotic patients with and without minimal hepatic encephalopathy

    International Nuclear Information System (INIS)

    The early diagnosis and treatment of cognitive impairment in cirrhotic patients is needed to improve the patients' daily living. In this study, alterations of regional cerebral blood flow (rCBF) were evaluated in cirrhotic patients using statistical parametric mapping (SPM). The relationships between rCBF and neuropsychological test, severity of disease and biochemical data were also assessed. 99mTc-ethyl cysteinate dimer single photon emission computed tomography was performed in 20 patients with non-alcoholic liver cirrhosis without overt hepatic encephalopathy (HE) and in 20 age-matched healthy subjects. Neuropsychological tests were performed in 16 patients; of these 7 had minimal HE. Regional CBF images were also analyzed in these groups using SPM. On SPM analysis, cirrhotic patients showed regions of significant hypoperfusion in the superior and middle frontal gyri, and inferior parietal lobules compared with the control group. These areas included parts of the premotor and parietal associated areas of the cortex. Among the cirrhotic patients, those with minimal HE had regions of significant hypoperfusion in the cingulate gyri bilaterally as compared with those without minimal HE. Abnormal function in the above regions may account for the relatively selective neuropsychological deficits in the cognitive status of patients with cirrhosis. These findings may be important in the identification and management of cirrhotic patients with minimal HE. (author)

  4. iNOS-dependent increase in colonic mucus thickness in DSS-colitic rats.

    Directory of Open Access Journals (Sweden)

    Olof Schreiber

    Full Text Available AIM: To investigate colonic mucus thickness in vivo in health and during experimental inflammatory bowel disease. METHODS: Colitis was induced with 5% DSS in drinking water for 8 days prior to experiment, when the descending colonic mucosa of anesthetized rats was studied using intravital microscopy. Mucus thickness was measured with micropipettes attached to a micromanipulator. To assess the contributions of NOS and prostaglandins in the regulation of colonic mucus thickness, the non-selective NOS-inhibitor L-NNA (10 mg/kg bolus followed by 3 mg/kg/h, the selective iNOS-inhibitor L-NIL (10 mg/kg bolus followed by 3 mg/kg/h and the non-selective COX-inhibitor diclofenac (5 mg/kg were administered intravenously prior to experiment. To further investigate the role of iNOS in the regulation of colonic mucus thickness, iNOS -/- mice were used. RESULTS: Colitic rats had a thicker firmly adherent mucus layer following 8 days of DSS treatment than untreated rats (88±2 µm vs 76±1 µm. During induction of colitis, the thickness of the colonic mucus layer initially decreased but was from day 3 significantly thicker than in untreated rats. Diclofenac reduced the mucus thickness similarly in colitic and untreated rats (-16±5 µm vs -14±2 µm. While L-NNA had no effect on colonic mucus thickness in DSS or untreated controls (+3±2 µm vs +3±1 µm, L-NIL reduced the mucus thickness significantly more in colitic rats than in controls (-33±4 µm vs -10±3 µm. The importance of iNOS in regulating the colonic mucus thickness was confirmed in iNOS-/- mice, which had thinner colonic mucus than wild-type mice (35±3 µm vs 50±2 µm, respectively. Furthermore, immunohistochemistry revealed increased levels of iNOS in the colonic surface epithelium following DSS treatment. CONCLUSION: Both prostaglandins and nitric oxide regulate basal colonic mucus thickness. During onset of colitis, the thickness of the mucus layer is initially reduced followed by an i

  5. Bone plasticity in response to exercise is sex-dependent in rats.

    Directory of Open Access Journals (Sweden)

    Wagner S Vicente

    Full Text Available PURPOSE: To characterize the potential sexual dimorphism of bone in response to exercise. METHODS: Young male and female Wistar rats were either submitted to 12 weeks of exercise or remained sedentary. The training load was adjusted at the mid-trial (week 6 by the maximal speed test. A mechanical test was performed to measure the maximal force, resilience, stiffness, and fracture load. The bone structure, formation, and resorption were obtained by histomorphometric analyses. Type I collagen (COL I mRNA expression and tartrate-resistant acid phosphatase (TRAP mRNA expression were evaluated by quantitative real-time PCR (qPCR. RESULTS: The male and female trained rats significantly improved their maximum speed during the maximal exercise test (main effect of training; p<0.0001. The male rats were significantly heavier than the females, irrespective of training (main effect of sex; p<0.0001. Similarly, both the weight and length of the femur were greater for the male rats when compared with the females (main effect of sex; p<0.0001 and p<0.0001, respectively. The trabecular volume was positively affected by exercise in male and female rats (main effect of training; p = 0.001, whereas the trabecular thickness, resilience, mineral apposition rate, and bone formation rate increased only in the trained males (within-sex comparison; p<0.05 for all parameters, demonstrating the sexual dimorphism in response to exercise. Accordingly, the number of osteocytes increased significantly only in the trained males (within-sex comparison; p<0.05. Pearson's correlation analyses revealed that the COL I mRNA expression and TRAP mRNA expression were positively and negatively, respectively, related to the parameters of bone remodeling obtained from the histomorphometric analysis (r = 0.59 to 0.85; p<0.05. CONCLUSION: Exercise yielded differential adaptations with respect to bone structure, biomechanical proprieties, and molecular signaling in male and female

  6. The morphological study of age-dependent effects in rat thyroids after γ-ray irradiation

    International Nuclear Information System (INIS)

    The purpose of this paper is to identify the differences in age-related harmful effects of the thyroid gland to ionizing radiation. The infant (0.5 month) and adult rats (2.5,6 and 15 months, respectively) were exposed to single γ-ray neck irradiation (0 Gy, as control, 0.5 Gy, 2 Gy, 4 Gy, 8 Gy, 16 Gy). The structure of irradiated thyroid gland under light and transmission electron microscope were observed at 6 weeks after partial irradiation. Some morphometric parameters were measured under light microscope. The results showed that the infant rat thyroids changed significantly after 0.5 Gy, but the adult thyroids expressed similar response after more than 2 Gy. Analyses of these data and information on pathology suggested that the infant thyroids were more radiosensitive than the adult ones

  7. Exercise induces age-dependent changes on epigenetic parameters in rat hippocampus: a preliminary study

    OpenAIRE

    Elsner, Viviane Rostirola; Lovatel, Gisele Agustini; Moysés, Felipe; Bertoldi, Karine; Spindler, Christiano; Cechinel, Laura Reck; Muotri, Alysson; Siqueira, Ionara Rodrigues

    2012-01-01

    Regular exercise improves learning and memory, including during aging process. Interestingly, the imbalance of epigenetic mechanisms has been linked to age-related cognitive deficits. However, studies about epigenetic alterations after exercise during the aging process are rare. In this preliminary study we investigated the effect of aging and exercise on DNA methyltransferases (DNMT1 and DNMT3b) and H3-K9 methylation levels in hippocampus from 3 and 20-months aged Wistar rats. The animals we...

  8. Use-Dependent Learning and Memory of the Hering-Breuer Inflation Reflex in Rat

    OpenAIRE

    MacDonald, Shawna M.; Tin, Chung; Song, Gang; Poon, Chi-Sang

    2008-01-01

    The classic Hering-Breuer inflation reflex (HBIR) is a widely-held tenet for understanding the lung volume-related vagal control of respiratory rhythm. Recent evidence, however, has revealed that the fictive HBIR elicited by electrical vagal stimulation in rats is not static but may be attenuated centrally by two forms of nonassociative learning (habituation and desensitization) that continually mitigate the reflex effects with exponential adaptations like a differentiator or high-pass filter...

  9. Time-Dependent Alterations in Rat Macrovessels with Type 1 Diabetes

    OpenAIRE

    Yvonne Searls; Irina V. Smirnova; Lisa VanHoose; Barbara Fegley; Rajprasad Loganathan; Lisa Stehno-Bittel

    2012-01-01

    Vascular complications are associated with the progressive severity of diabetes, resulting in significant morbidity and mortality. This study quantifies functional vascular parameters and macrovascular structure in a rat model of type 1 diabetes. While there was no difference in the systemic arterial elastance (Ea) with 50 days of diabetes, changes were noted in the aorta and femoral artery including increased tunica media extracellular matrix content, decreased width of both the media and i...

  10. Culture of hormone-dependent functional epithelial cells from rat thyroids.

    OpenAIRE

    Ambesi-Impiombato, F S; Parks, L A; Coon, H G

    1980-01-01

    Primary cultures of rat thyroid cells were made in medium supplemented with 0.1--0.5% calf serum and containing six hormones or growth factors: insulin, thyrotropin, transferrin, hydrocortisone, somatostatin, and glycyl-L-histidyl-L-lysine acetate. The FRTL strain was purified by successive colonial isolations and was found to maintain highly differentiated features (secretion into the culture medium of physiological amounts of thyroglobulin and concentration of iodide by 100-fold). The FRTL ...

  11. Time-dependent changes of autophagy and apoptosis in lipopolysaccharide-induced rat acute lung injury

    OpenAIRE

    Li Lin; Lijun Zhang; Liangzhu Yu; Lu Han; Wanli Ji; Hui Shen; Zhenwu Hu

    2016-01-01

    Objective(s): Abnormal lung cell death including autophagy and apoptosis is the central feature in acute lung injury (ALI). To identify the cellular mechanisms and the chronology by which different types of lung cell death are activated during lipopolysaccharide (LPS)-induced ALI, we decided to evaluate autophagy (by LC3-II and autophagosome) and apoptosis (by caspase-3) at different time points after LPS treatment in a rat model of LPS-induced ALI. Materials and Methods: Sprague-Dawley ra...

  12. Similar withdrawal severity in adolescents and adults in a rat model of alcohol dependence

    OpenAIRE

    Morris, S.A.; Kelso, M.L.; Liput, D.J.; Marshall, S A; Nixon, K.

    2010-01-01

    Alcohol use during adolescence leads to increased risk of developing an alcohol use disorder (AUD) during adulthood. Converging evidence suggests that this period of enhanced vulnerability for developing an AUD may be due to the adolescent’s unique sensitivity and response to alcohol. Adolescent rats have been shown to be less sensitive to alcohol intoxication and withdrawal susceptibility; however age differences in ethanol pharmacokinetics may underlie these effects. Therefore, this study i...

  13. Age-Dependent Reductions in Mitochondrial Respiration are Exacerbated by Calcium in the Female Rat Heart

    OpenAIRE

    Hunter, J. Craig; Machikas, Alexandra M.; Korzick, Donna H.

    2012-01-01

    Cardiovascular disease mortality increases rapidly following menopause by poorly defined mechanisms. Since mitochondrial function and Ca2+ sensitivity are important regulators of cell death following myocardial ischemia, we sought to determine if aging and/or estrogen deficiency (ovx) increased mitochondrial Ca2+ sensitivity. Mitochondrial respiration was measured in ventricular mitochondria isolated from adult (6mo; n=26) and aged (24mo; n=25), intact or ovariectomized female rats using the ...

  14. Strain Dependent Effects of Prenatal Stress on Gene Expression in the Rat Hippocampus

    OpenAIRE

    Neeley, Eric W.; Berger, Ralph; Koenig, James I.; Leonard, Sherry

    2011-01-01

    Multiple animal models have been developed to recapitulate phenotypes of the human disease, schizophrenia. A model that simulates many of the cognitive and sensory deficits of the disorder is the use of random variable prenatal stress (PS) in the rat. These deficits suggest a molecular origin in the hippocampus, a brain region that plays a role in the regulation of stress. To study both hippocampal gene expression changes in offspring of prenatally stressed dams and to address genetic variabi...

  15. Ethionine-dependent inhibition of acute-phase plasma protein synthesis in the rat.

    OpenAIRE

    Kasperczyk, H.; Koj, A

    1983-01-01

    Ethionine administered intraperitoneally to rats suffering from turpentine-induced inflammation preferentially reduced incorporation of 14C-leucine into fibrinogen, haptoglobin and other acute-phase proteins. The inhibitory effect was observed both in vivo and in liver slices obtained from ethionine-treated donors, while addition of ethionine to liver slices in vitro led to general reduction of synthesis of all liver and plasma proteins, including albumin. For comparison, the effects of galac...

  16. Hypertrophy dependent doubling of L-cells in Roux-en-Y gastric bypass operated rats.

    Directory of Open Access Journals (Sweden)

    Carl Frederik Hansen

    Full Text Available BACKGROUND AND AIMS: Roux-en-Y gastric bypass (RYGB leads to a rapid remission of type 2 diabetes mellitus (T2DM, but the underlying mode of action remains incompletely understood. L-cell derived gut hormones such as glucagon-like peptide-1 (GLP-1 and peptide YY (PYY are thought to play a central role in the anti-diabetic effects of RYGB; therefore, an improved understanding of intestinal endocrine L-cell adaptability is considered pivotal. METHODS: The full rostrocaudal extension of the gut was analyzed in rats after RYGB and in sham-operated controls ad libitum fed or food restricted to match the body weight of RYGB rats. Total number of L-cells, as well as regional numbers, densities and mucosa volumes were quantified using stereological methods. Preproglucagon and PYY mRNA transcripts were quantified by qPCR to reflect the total and relative hormone production capacity of the L-cells. RESULTS: RYGB surgery induced hypertrophy of the gut mucosa in the food exposed regions of the small intestine coupled with a doubling in the total number of L-cells. No changes in L-cell density were observed in any region regardless of surgery or food restriction. The total gene expression capacity of the entire gut revealed a near 200% increase in both PYY and preproglucagon mRNA levels in RYGB rats associated with both increased L-cell number as well as region-specific increased transcription per cell. CONCLUSIONS: Collectively, these findings indicate that RYGB in rats is associated with gut hypertrophy, an increase in L-cell number, but not density, and increased PYY and preproglucagon gene expression. This could explain the enhanced gut hormone dynamics seen after RYGB.

  17. Dose dependent effects of inhaled ethylene oxide on spermatogenesis in rats.

    OpenAIRE

    Mori, K; Kaido, M.; Fujishiro, K.; Inoue, N.; Koide, O; Hori, H; Tanaka, I

    1991-01-01

    Male Wistar rats were exposed to ethylene oxide (EO) at concentrations of 50, 100, or 250 ppm for six hours a day, on five days a week for 13 weeks. Dose effect relations of inhaled EO on spermatogenesis were evaluated from testicular and epididymal weights, histopathological changes and lactate dehydrogenase X (LDH X) activity in the testis, and sperm counts and sperm head abnormalities in the epididymis. At 250 ppm, a decrease in epididymal weights, slight degenerations in the seminiferous ...

  18. Effect of morin, a flavonoid against DOCA-salt hypertensive rats:a dose dependent study

    Institute of Scientific and Technical Information of China (English)

    Prahalathan P; Kumar S; Raja B

    2012-01-01

    Objective:To determine the protective effect of morin, a flavonoid against deoxycorticosterone acetate (DOCA)-salt induced hypertension in male Wistar rats. Methods: Hypertension was induced in uninephrectomized rats by weekly twice subcutaneous injection of DOCA (25 mg/kg bw) and 1% NaCl in the drinking water for six consecutive weeks. Effect of morin against DOCA-salt induced hypertension was evaluated by measuring blood pressure and performing biochemical estimations and histopathological examination of renal tissues. Results: DOCA-salt hypertensive rats showed considerably increased systolic and diastolic blood pressure, serum hepatic marker enzyme activities such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) and renal function markers (urea, uric acid and creatinine) in plasma. Oral administration of morin (25, 50 and 75 mg/kg bw) brought back all the above parameters to near normal level. Histopathology of kidney also confirmed the biochemical findings of this study. The effect at a dose of 50 mg/kg bw of morin was more pronounced than that of the other two doses (25 and 75 mg/kg bw). Conclusions:These findings indicate that morin exhibits strong antihypertensive effect against DOCA-salt induced hypertension.

  19. Penicillin-induced epilepsy model in rats: dose-dependant effect on hippocampal volume and neuron number.

    Science.gov (United States)

    Akdogan, Ilgaz; Adiguzel, Esat; Yilmaz, Ismail; Ozdemir, M Bulent; Sahiner, Melike; Tufan, A Cevik

    2008-10-22

    This study was designed to evaluate the penicillin-induced epilepsy model in terms of dose-response relationship of penicillin used to induce epilepsy seizure on hippocampal neuron number and hippocampal volume in Sprague-Dawley rats. Seizures were induced with 300, 500, 1500 and 2000IU of penicillin-G injected intracortically in rats divided in four experimental groups, respectively. Control group was injected intracortically with saline. Animals were decapitated on day 7 of treatment and brains were removed. The total neuron number of pyramidal cell layer from rat hippocampus was estimated using the optical fractionator method. The volume of same hippocampal areas was estimated using the Cavalieri method. Dose-dependent decrease in hippocampal neuron number was observed in three experimental groups (300, 500 and 1500IU of penicillin-G), and the effects were statistically significant when compared to the control group (P<0.009). Dose-dependent decrease in hippocampal volume, on the other hand, was observed in all three of these groups; however, the difference compared to the control group was only statistically significant in 1500IU of penicillin-G injected group (P<0.009). At the dose of 2000IU penicillin-G, all animals died due to status seizures. These results suggest that the appropriate dose of penicillin has to be selected for a given experimental epilepsy study in order to demonstrate the relevant epileptic seizure and its effects. Intracortical 1500IU penicillin-induced epilepsy model may be a good choice to practice studies that investigate neuroprotective mechanisms of the anti-epileptic drugs.

  20. Effects of early life trauma are dependent on genetic predisposition: a rat study

    Directory of Open Access Journals (Sweden)

    Russell Vivienne A

    2011-05-01

    Full Text Available Abstract Background Trauma experienced early in life increases the risk of developing a number of psychological and/or behavioural disorders. It is unclear, however, how genetic predisposition to a behavioural disorder, such as attention-deficit/hyperactivity disorder (ADHD, modifies the long-term effects of early life trauma. There is substantial evidence from family and twin studies for susceptibility to ADHD being inherited, implying a strong genetic component to the disorder. In the present study we used an inbred animal model of ADHD, the spontaneously hypertensive rat (SHR, to investigate the long-term consequences of early life trauma on emotional behaviour in individuals predisposed to developing ADHD-like behaviour. Methods We applied a rodent model of early life trauma, maternal separation, to SHR and Wistar-Kyoto rats (WKY, the normotensive control strain from which SHR were originally derived. The effects of maternal separation (removal of pups from dam for 3 h/day during the first 2 weeks of life on anxiety-like behaviour (elevated-plus maze and depressive-like behaviour (forced swim test were assessed in prepubescent rats (postnatal day 28 and 31. Basal levels of plasma corticosterone were measured using radioimmunoassay. Results The effect of maternal separation on SHR and WKY differed in a number of behavioural measures. Similar to its reported effect in other rat strains, maternal separation increased the anxiety-like behaviour of WKY (decreased open arm entries but not SHR. Maternal separation increased the activity of SHR in the novel environment of the elevated plus-maze, while it decreased that of WKY. Overall, SHR showed a more active response in the elevated plus-maze and forced swim test than WKY, regardless of treatment, and were also found to have higher basal plasma corticosterone compared to WKY. Maternal separation increased basal levels of plasma corticosterone in SHR females only, possibly through adaptive

  1. Time-series analysis of sleep wake stage of rat EEG using time-dependent pattern entropy

    Science.gov (United States)

    Ishizaki, Ryuji; Shinba, Toshikazu; Mugishima, Go; Haraguchi, Hikaru; Inoue, Masayoshi

    2008-05-01

    We performed electroencephalography (EEG) for six male Wistar rats to clarify temporal behaviors at different levels of consciousness. Levels were identified both by conventional sleep analysis methods and by our novel entropy method. In our method, time-dependent pattern entropy is introduced, by which EEG is reduced to binary symbolic dynamics and the pattern of symbols in a sliding temporal window is considered. A high correlation was obtained between level of consciousness as measured by the conventional method and mean entropy in our entropy method. Mean entropy was maximal while awake (stage W) and decreased as sleep deepened. These results suggest that time-dependent pattern entropy may offer a promising method for future sleep research.

  2. A toxic extract of the marine phytoflagellate Prymnesium parvum induces calcium-dependent release of glutamate from rat brain synaptosomes.

    Science.gov (United States)

    Mariussen, Espen; Nelson, George Nicholas; Fonnum, Frode

    2005-01-01

    Blooms of the marine phytoflagellate Prymnesium parvum produced mass mortality of fish in Norway and many other parts of the world. The effects of a purified algae extract of P. parvum on transmitter release from rat brain synaptosomes were studied to characterize its toxic action. Synaptosomes are detached nerve terminals and represent a simple system that has retained the machinery for uptake, synthesis, storage, and release of neurotransmitters. A crude methanol extract of P. parvum was purified by reverse-phase column for fast protein liquid chromatography (FPLC). The purified extract stimulated Ca2+-dependent spontaneous release of glutamate in a concentration-dependent manner. The release was increased by addition of extracellular Ca2+. The release of glutamate was suppressed by the Ca2+-channel blockers flunarizine (10 microM), diltiazem (10 microM), and verapamil (10 microM). The stimulation of release of glutamate from rat brain synaptosomes induced by the toxin may be due to an ionophorelike property of the algae extract such as previously reported for the potent algal toxin maitotoxin. At high concentrations the toxin primarily acts as a powerful lytic agent. PMID:15739805

  3. Time course of the estradiol-dependent induction of oxytocin receptor binding in the ventromedial hypothalamic nucleus of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, A.E.; Ball, G.F.; Coirini, H.; Harbaugh, C.R.; McEwen, B.S.; Insel, T.R. (National Institute of Mental Health, Poolesville, MD (USA))

    1989-09-01

    Oxytocin (OT) transmission is involved in the steroid-dependent display of sexual receptivity in rats. One of the biochemical processes stimulated by the ovarian steroid 17 beta-estradiol (E2) that is relevant to reproduction is the induction of OT receptor binding in the ventromedial hypothalamic nucleus (VMN). The purpose of these experiments was to determine if E2-induced changes in OT receptor binding in the VMN occur within a time frame relevant to cyclic changes in ovarian steroid secretion. OT receptor binding was measured in the VMN of ovariectomized rats implanted for 0-96 h with E2-containing Silastic capsules. The rate of decay of OT receptor binding was measured in another group of animals 6-48 h after capsule removal. Receptors were labeled with the specific OT receptor antagonist ({sup 125}I)d(CH2)5(Tyr(Me)2,Thr4,Tyr-NH2(9))OVT, and binding was measured with quantitative autoradiographic methods. In addition, plasma E2 levels and uterine weights were assessed in animals from each treatment condition. Significant increases in E2-dependent OT receptor binding and uterine weight occurred within 24 h of steroid treatment. After E2 withdrawal, OT receptor binding and uterine weight decreased significantly within 24 h. These results are consistent with the hypothesis that steroid modulation of OT receptor binding is necessary for the induction of sexual receptivity.

  4. Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats.

    Science.gov (United States)

    Spiga, Saturnino; Talani, Giuseppe; Mulas, Giovanna; Licheri, Valentina; Fois, Giulia R; Muggironi, Giulia; Masala, Nicola; Cannizzaro, Carla; Biggio, Giovanni; Sanna, Enrico; Diana, Marco

    2014-09-01

    Alcoholism involves long-term cognitive deficits, including memory impairment, resulting in substantial cost to society. Neuronal refinement and stabilization are hypothesized to confer resilience to poor decision making and addictive-like behaviors, such as excessive ethanol drinking and dependence. Accordingly, structural abnormalities are likely to contribute to synaptic dysfunctions that occur from suddenly ceasing the use of alcohol after chronic ingestion. Here we show that ethanol-dependent rats display a loss of dendritic spines in medium spiny neurons of the nucleus accumbens (Nacc) shell, accompanied by a reduction of tyrosine hydroxylase immunostaining and postsynaptic density 95-positive elements. Further analysis indicates that "long thin" but not "mushroom" spines are selectively affected. In addition, patch-clamp experiments from Nacc slices reveal that long-term depression (LTD) formation is hampered, with parallel changes in field potential recordings and reductions in NMDA-mediated synaptic currents. These changes are restricted to the withdrawal phase of ethanol dependence, suggesting their relevance in the genesis of signs and/or symptoms affecting ethanol withdrawal and thus the whole addictive cycle. Overall, these results highlight the key role of dynamic alterations in dendritic spines and their presynaptic afferents in the evolution of alcohol dependence. Furthermore, they suggest that the selective loss of long thin spines together with a reduced NMDA receptor function may affect learning. Disruption of this LTD could contribute to the rigid emotional and motivational state observed in alcohol dependence. PMID:25122682

  5. Strain-dependent effects of acute caffeine on anxiety-related behavior in PVG/c, Long-Evans and Wistar rats.

    Science.gov (United States)

    Hughes, Robert N; Hancock, Nicola J

    2016-01-01

    To assess the possibility that acute caffeine's behavioral action might depend on rats' strain, effects of 50mg/kg of the drug were observed on activity, anxiety-related behavior and habituation learning in male and female rats from three different strains, namely PVG/c, Long-Evans and Wistar. All subjects were tested in an open field, an elevated plus maze and a light-dark box. For the three strains combined, increased occupancy of the center of the open field and entries of the open plus-maze arms with caffeine suggested caffeine-induced anxiolysis, whereas increased grooming in the open field, decreased rearing in the plus maze and increased risk assessment in the light-dark box were consistent with anxiogenesis. Caffeine also reduced open-field rearing only for PVG/c rats, and entries into and occupation of the light side of the light-dark box only for Long-Evans rats, and increased total defecation in the three types of apparatus for all three strains combined. Overall, caffeine appeared to be mainly anxiogenic. The drug also increased open-field ambulation for PVG/c rats and walking for all rats, but decreased open-field ambulation and entries into the plus maze closed arms for Wistar rats alone. In general, Wistar rats appeared to be the least and Long-Evans the most anxious of the three strains investigated. Caffeine also decreased within-session habituation of open-field ambulation for PVG/c rats alone, thereby suggesting strain-dependent interference with non-associative learning and short-term memory. Several overall sex differences were also observed that supported female rats being more active and less anxious than males. PMID:26577750

  6. Strain-dependent effects of acute caffeine on anxiety-related behavior in PVG/c, Long-Evans and Wistar rats.

    Science.gov (United States)

    Hughes, Robert N; Hancock, Nicola J

    2016-01-01

    To assess the possibility that acute caffeine's behavioral action might depend on rats' strain, effects of 50mg/kg of the drug were observed on activity, anxiety-related behavior and habituation learning in male and female rats from three different strains, namely PVG/c, Long-Evans and Wistar. All subjects were tested in an open field, an elevated plus maze and a light-dark box. For the three strains combined, increased occupancy of the center of the open field and entries of the open plus-maze arms with caffeine suggested caffeine-induced anxiolysis, whereas increased grooming in the open field, decreased rearing in the plus maze and increased risk assessment in the light-dark box were consistent with anxiogenesis. Caffeine also reduced open-field rearing only for PVG/c rats, and entries into and occupation of the light side of the light-dark box only for Long-Evans rats, and increased total defecation in the three types of apparatus for all three strains combined. Overall, caffeine appeared to be mainly anxiogenic. The drug also increased open-field ambulation for PVG/c rats and walking for all rats, but decreased open-field ambulation and entries into the plus maze closed arms for Wistar rats alone. In general, Wistar rats appeared to be the least and Long-Evans the most anxious of the three strains investigated. Caffeine also decreased within-session habituation of open-field ambulation for PVG/c rats alone, thereby suggesting strain-dependent interference with non-associative learning and short-term memory. Several overall sex differences were also observed that supported female rats being more active and less anxious than males.

  7. Comparative study of bacterial infection prevalence between cirrhotic patients with and without upper gastrointestinal bleeding

    Directory of Open Access Journals (Sweden)

    Delvone Almeida

    2001-06-01

    Full Text Available Bacterial infection is a frequent complication in patients with chronic liver disease, mainly during the advanced stages. There is evidence that the main factors that contribute to a predisposition to infection in cirrhotic patients are related to hepatic failure with consequent immunodeficiency. Invasive procedures (diagnostic or therapeutic can predispose to bacterial infections, and upper gastrointestinal bleeding (UGB is considered a potentially important risk factor. A group of cirrhotic patients (child B and C Pugh groups were evaluated retrospectively by chart reviews regarding the prevalence of bacterial infection during hospitalization to determine whether UGB was a risk factor. An infection was considered present if a specific organ system was identified or if fever (>38ºC persisted for more than 24 hours with associated leukocytosis. Spontaneous bacterial peritonitis was based on classical criteria. Eighty-nine patients were evaluated. Fourty-six patients presented with UGB, and 43 patients had no UGB (control. There were infections recorded in 25/46 (54% patients with UGB, and 15/43 (35% in those without UGB (p=0.065. The ratio of the number of infections/admitted patients, was significantly larger in the group with UGB (0.78 ± 0.89 vs. 0.39 ± 0.62; p=0.028 since patients had more than one infection. In the UGB group compared to non UGB group, ascites was more frequent (67% vs. 42%; p=0.027; they were more likely to have undergone endoscopic procedures (p<0.001 and the mean ± SD for platelets count was smaller (96,114 ± 57,563 vs. 145,674 ± 104,083; p=0.007. The results show that UGB is an important contribution to bacterial infection among Child B and C cirrhotic patients.

  8. Serum interleukin-6 in the diagnosis of bacterial infection in cirrhotic patients

    Science.gov (United States)

    Wu, Yinlian; Wang, Mingfang; Zhu, Yueyong; Lin, Su

    2016-01-01

    Abstract Background: The diagnostic accuracy of interleukin-6 (IL-6) in predicting bacterial infection in cirrhotic patients remains unclear. The aim of this meta-analysis is to explore the potential diagnostic value of IL-6 in cirrhotic patients. Methods: We systematically searched PubMed, Embase (via OvidSP), Web of Science, the Cochrane Library, and Scopus for studies published from inception to October 2015. Studies were enrolled if they included assessment of the accuracy of IL-6 in the diagnosis of bacterial infection in cirrhotic patients and provided sufficient data to construct a 2 × 2 contingency table. Results: Totally, 535 studies were searched in the initial database and finally 6 studies involving 741 patients were included for the final analysis. The pooled sensitivity, specificity and diagnostic odds ratio were 0.85 (95% confidence interval [CI], 0.64–0.94), 0.91 (95% CI, 0.80–0.96) and 52.89 (95% CI, 15.21–183.86), respectively. The pooled positive likelihood ratio was 8.99 (95% CI, 4.13–19.55) and the pooled negative likelihood ratio was 0.17 (95% CI, 0.07–0.43). The area under the receiver operating characteristic curve was 0.94 (95% CI, 0.92–0.96). Conclusion: This meta-analysis suggests IL-6 has a high diagnostic value for the differentiation of bacterial infection in patients with cirrhosis. PMID:27741137

  9. What we should know about portal vein thrombosis in cirrhotic patients: A changing perspective

    Institute of Scientific and Technical Information of China (English)

    Francesca Romana Ponziani; Maria Assunta Zocco; Matteo Garcovich; Francesca D'Aversa; Davide Roccarina; Antonio Gasbarrini

    2012-01-01

    Portal vein thrombosis (PVT) is one of the most common complications occurring during the natural course of liver cirrhosis.Even though PVT is often asymptomatic,the worsening of liver function,an unexpected episode of gastrointestinal bleeding or ascitic decompensation may be landmarks of PVT development.Beyond these clinical manifestations,it is debated whether PVT really has an impact on liver cirrhosis natural history or rather represents only one of its consequences.Probably PVT development should not only be considered as a matter of impaired blood flow or pro-coagulation tendency.On one hand,PVT seems a consequence of the worsening in portal vein outflow due to the increased hepatic resistance in cirrhotic livers.On the other hand,vascular microthrombosis secondary to necroinflammation may cause liver ischemia and infarction,with loss of hepatic tissue (parenchymal extinction) which is replaced by fibrotic tissue.Therefore,PVT might also be considered as the overt manifestation of the liver fibrosing process evolution and anticoagulant therapy may thus have microscopic indirect effects also on the progression of liver disease.At present,a connection between PVT development and the progression of liver fibrosis/cirrhosis has not yet been demonstrated.Nevertheless,it is not clear if PVT development may worsen cirrhotic patients' outcome by itself.Some authors tried to assess liver transplant benefit in PVT cirrhotic patients but data are contrasting.In this review,we will try to answer these questions,providing a critical analysis of data reported in literature.

  10. Acute kidney injury in cirrhotic patients undergoing contrast-enhanced computed tomography.

    Science.gov (United States)

    Filomia, Roberto; Maimone, Sergio; Caccamo, Gaia; Saitta, Carlo; Visconti, Luca; Alibrandi, Angela; Caloggero, Simona; Bottari, Antonio; Franzè, Maria Stella; Gambino, Carmine Gabriele; Lembo, Tindaro; Oliva, Giovanni; Cacciola, Irene; Raimondo, Giovanni; Squadrito, Giovanni

    2016-09-01

    Contrast medium administration is one of the leading causes of acute kidney injury (AKI) in different clinical settings. The aim of the study was to investigate occurrence and predisposing factors of AKI in cirrhotic patients undergoing contrast-enhanced computed tomography (CECT).Datasets of 1279 consecutively hospitalized cirrhotic patients were retrospectively analyzed. Two hundred forty-nine of 1279 patients (mean age 64 ± 11 years, 165 male) who had undergone CECT were selected on the basis of the availability of serum creatinine (sCr) values evaluated before and after CECT (CECT group). In analogy, 203/1279 cases (mean age 66 ± 10 years, 132 male) who had not undergone CECT and had been tested twice for sCr in 7 days were also included as controls (Control group). AKI network criteria were employed to assess contrast-induced AKI (CI-AKI) development. Apart from lack of narrowed double sCr measurements, additional exclusion criteria were active bacterial infections, nephrotoxic drugs intake, and estimated glomerular filtration rate sCr values (OR: 0.124, 95% CI: 0.016-0.975; P = 0.047). In the CECT group, presence of ascites (OR: 2.796, 95% CI: 1.109-7.052; P = 0.029), female sex (OR: 0.192, 95% CI: 0.073-0.510; P = 0.001), and hyperazotemia (OR: 1.018, 95% CI: 1.001-1.037; P = 0.043) correlated with CI-AKI development at multivariate analysis.CI-AKI is a quite frequent occurrence in cirrhotic patients with female sex, presence of ascites, and hyperazotemia being the predisposing factors. PMID:27661025

  11. Acute kidney injury in cirrhotic patients undergoing contrast-enhanced computed tomography

    Science.gov (United States)

    Filomia, Roberto; Maimone, Sergio; Caccamo, Gaia; Saitta, Carlo; Visconti, Luca; Alibrandi, Angela; Caloggero, Simona; Bottari, Antonio; Franzè, Maria Stella; Gambino, Carmine Gabriele; Lembo, Tindaro; Oliva, Giovanni; Cacciola, Irene; Raimondo, Giovanni; Squadrito, Giovanni

    2016-01-01

    Abstract Contrast medium administration is one of the leading causes of acute kidney injury (AKI) in different clinical settings. The aim of the study was to investigate occurrence and predisposing factors of AKI in cirrhotic patients undergoing contrast-enhanced computed tomography (CECT). Datasets of 1279 consecutively hospitalized cirrhotic patients were retrospectively analyzed. Two hundred forty-nine of 1279 patients (mean age 64 ± 11 years, 165 male) who had undergone CECT were selected on the basis of the availability of serum creatinine (sCr) values evaluated before and after CECT (CECT group). In analogy, 203/1279 cases (mean age 66 ± 10 years, 132 male) who had not undergone CECT and had been tested twice for sCr in 7 days were also included as controls (Control group). AKI network criteria were employed to assess contrast-induced AKI (CI-AKI) development. Apart from lack of narrowed double sCr measurements, additional exclusion criteria were active bacterial infections, nephrotoxic drugs intake, and estimated glomerular filtration rate sCr values (OR: 0.124, 95% CI: 0.016–0.975; P = 0.047). In the CECT group, presence of ascites (OR: 2.796, 95% CI: 1.109–7.052; P = 0.029), female sex (OR: 0.192, 95% CI: 0.073–0.510; P = 0.001), and hyperazotemia (OR: 1.018, 95% CI: 1.001–1.037; P = 0.043) correlated with CI-AKI development at multivariate analysis. CI-AKI is a quite frequent occurrence in cirrhotic patients with female sex, presence of ascites, and hyperazotemia being the predisposing factors. PMID:27661025

  12. Antiviral therapy in hepatitis C virus cirrhotic patients in compensated and decompensated condition

    Institute of Scientific and Technical Information of China (English)

    Angelo Iacobellis; Antonio Ippolito; Angelo Andriulli

    2008-01-01

    The main goals of treating cirrhotic patients with antiviral therapy are to attain sustained viral clearance (SVR), halt disease progression, and prevent re-infection of the liver graft. However, while the medical need is great, the use of interferon and ribavirin might expose these patients to severe treated-related side effects as a large proportion of them have pre-existing hematological cytopenias. We have reviewed potential benefits and risks associated with antiviral drugs in patients with liver cirrhosis, due to hepatitis C virus (HCV) infection. In cases presenting with bridging fibrosis or cirrhosis, current regimens of antiviral therapy have attained a 44%-48% rate of SVR. In cirrhotic patients with portal hypertension, the SVR rate was 22% overall, 12.5% in patients with genotype 1, and 66.7% in those with genotypes 2 and 3 following therapy with low doses of either Peg-IFN alpha-2b and of ribavirin. In patients with decompensated cirrhosis, full dosages of Peg-IFN alpha-2b and of ribavirin produced a SVR rate of 35% overall, 16% in patients with genotype 1 and 4, and 59% in those with genotype 2 and 3. Use of hematological cytokines will either ensure full course of treatment to be accomplished with and prevent development of treatment-associated side effects. Major benefits after HCV eradication were partial recovery of liver metabolic activity, prevention of hepatitis C recurrence after transplantation, and removal of some patients from the waiting list for liver transplant. Several observations highlighted that therapy is inadvisable for individuals with poor hepatic reserve (ChUd-Pugh-Turcotte score ≥ 10). Although SVR rates are low in decompensated cirrhotics due to hepatitis C, these patients have the most to gain as successful antiviral therapy is potentially lifesaving. C 2008 The W.1G Press. All dghts reserved.

  13. New concepts in liver cirrhosis: clinical significance of sarcopenia in cirrhotic patients.

    Science.gov (United States)

    Montano-Loza, A J

    2013-06-01

    The natural history of cirrhotic patients is highly variable due to several factors including hepatic synthetic function, presence and degree of portal hypertension, the cause of cirrhosis, the possibility of resolution of the underlying damaging process, and the occurrence of liver cancer. Currently, D'Amico stage classification and Child-Pugh and Model for End-Stage Liver Disease (MELD) scores constitute the best tools to predict mortality in patients with cirrhosis; however, one of their main limitations is the lack of evaluation of the nutritional and functional status. Most widely recognized complications in cirrhotic patients include ascites, hepatic encephalopathy, variceal bleeding, kidney dysfunction, and hepatocellular carcinoma; however, sarcopenia or severe muscle wasting is one of the most common and frequently hidden complications which negatively impact survival, quality of life, and response to stressor, such as infection and surgery. In this review, we discuss the current accepted and new methods to evaluate prognosis in cirrhosis, and also analyze the current knowledge regarding incidence and clinical impact of malnutrition and sarcopenia in cirrhosis and their impact after liver transplantation. We also discuss existing and potential novel therapeutic strategies for malnutrition in cirrhosis, emphasizing the recognition of sarcopenia in cirrhosis in an effort to improve survival and reduced morbidity related to cirrhosis. Finally, we propose that future studies including sarcopenia with the MELD score may allow better prediction of mortality among cirrhotic patients waiting for liver transplantation; however, due to the worldwide shortage of organs for transplants, one of the vital clinical questions is the feasibility to treat sarcopenia in cirrhosis without the need of liver transplant.

  14. Colonic GLP-2 is not sufficient to promote jejunal adaptation in a PN-dependent rat model of human short bowel syndrome

    DEFF Research Database (Denmark)

    Koopmann, Matthew C; Liu, Xiaowen; Boehler, Christopher J;

    2009-01-01

    BACKGROUND: Bowel resection may lead to short bowel syndrome (SBS), which often requires parenteral nutrition (PN) due to inadequate intestinal adaptation. The objective of this study was to determine the time course of adaptation and proglucagon system responses after bowel resection in a PN......-dependent rat model of SBS. METHODS: Rats underwent jugular catheter placement and a 60% jejunoileal resection + cecectomy with jejunoileal anastomosis or transection control surgery. Rats were maintained exclusively with PN and killed at 4 hours to 12 days. A nonsurgical group served as baseline. Bowel growth...

  15. Ca2+-DEPENDENT PROTEIN KINASE C ISOFORMS ARE CRITICAL TO ESTRADIOL 17β-D-GLUCURONIDE-INDUCED CHOLESTASIS IN THE RAT

    OpenAIRE

    Crocenzi, Fernando A.; Enrique J Sánchez Pozzi; Ruiz, María Laura; Zucchetti, Andrés E.; Roma, Marcelo G.; Mottino, Aldo D.; Vore, Mary

    2008-01-01

    The endogenous estradiol metabolite estradiol 17β-D-glucuronide (E217G) induces an acute cholestasis in rat liver coincident with retrieval of the canalicular transporters Bsep (Abcc11) and Mrp2 (Abcc2) and their associated loss of function. We assessed the participation of Ca2+-dependent PKC isoforms (cPKC) in the cholestatic manifestations of E217G in the perfused rat liver (PRL) and in isolated rat hepatocyte couplets (IRHC). In the PRL, E217G (2 μmol/liver; intraportal, single injection) ...

  16. Cerebrolysin Attenuates Heat Shock Protein (HSP 72 KD) Expression in the Rat Spinal Cord Following Morphine Dependence and Withdrawal: Possible New Therapy for Pain Management

    OpenAIRE

    Sharma, Hari S.; Ali, Syed F; Patnaik, Ranjana; Zimmermann-Meinzingen, Sibilla; Sharma, Aruna; Muresanu, Dafin F

    2011-01-01

    The possibility that pain perception and processing in the CNS results in cellular stress and may influence heat shock protein (HSP) expression was examined in a rat model of morphine dependence and withdrawal. Since activation of pain pathways result in exhaustion of growth factors, we examined the influence of cerebrolysin, a mixture of potent growth factors (BDNF, GDNF, NGF, CNTF etc,) on morphine induced HSP expression. Rats were administered morphine (10 mg/kg, s.c. /day) for 12 days and...

  17. Differential effects of cystathionine-γ-lyase-dependent vasodilatory H2S in periadventitial vasoregulation of rat and mouse aortas.

    Directory of Open Access Journals (Sweden)

    Carolin Köhn

    Full Text Available BACKGROUND: Hydrogen sulfide (H(2S is a potent vasodilator. However, the complex mechanisms of vasoregulation by H(2S are not fully understood. We tested the hypotheses that (1 H(2S exerts vasodilatory effects by opening KCNQ-type voltage-dependent (K(v K(+ channels and (2 that H(2S-producing cystathionine-γ-lyase (CSE in perivascular adipose tissue plays a major role in this pathway. METHODOLOGY/PRINCIPAL FINDINGS: Wire myography of rat and mouse aortas was used. NaHS and 5-(4-hydroxyphenyl-3H-1,2-dithiole-3-thione (ADTOH were used as H(2S donors. KCNQ-type K(v channels were blocked by XE991. 4-Propargylglycine (PPG and ß-cyano-l-alanine (BCA, or 2-(aminooxy-acetic acid (AOAA were used as inhibitors of CSE or cystathionine-ß-synthase (CBS, respectively. NaHS and ADTOH produced strong vasorelaxation in rat and mouse aortas, which were abolished by KCNQ channel inhibition with XE991. Perivascular adipose tissue (PVAT exerted an anticontractile effect in these arteries. CSE inhibition by PPG and BCA reduced this effect in aortas from rats but not from mice. CBS inhibition with AOAA did not inhibit the anticontractile effects of PVAT. XE991, however, almost completely suppressed the anticontractile effects of PVAT in both species. Exogenous l-cysteine, substrate for the endogenous production of H(2S, induced vasorelaxation only at concentrations >5 mmol/l, an effect unchanged by CSE inhibition. CONCLUSIONS/SIGNFICANCE: Our results demonstrate potent vasorelaxant effects of H(2S donors in large arteries of both rats and mice, in which XE991-sensitive KCNQ-type channel opening play a pivotal role. CSE-H(2S seems to modulate the effect of adipocyte-derived relaxing factor in rat but not in mouse aorta. The present study provides novel insight into the interaction of CSE-H(2S and perivascular adipose tissue. Furthermore, with additional technical advances, a future clinical approach targeting vascular H(2S/KCNQ pathways to influence states of

  18. Non-O1, non-O139 Vibrio cholerae bacteraemia in a cirrhotic patient

    OpenAIRE

    Petsaris, O.; Nousbaum, J B; Quilici, M L; Le Coadou, G; PAYAN, C; Abalain, M L

    2010-01-01

    Vibrio cholerae serogroups O1 or O139 are the aetiological agents of cholera. The pathogenicity of non-O1, non-O139 V. cholerae is less well known. These worldwide bacteria are responsible for gastrointestinal infections or, more rarely, bacteraemia in patients with an underlying disease, leading to life-threatening complications. We report a case of non-O1, non-O139 V. cholerae bacteraemia due to a haemolytic strain in a cirrhotic patient. Early antibiotherapy allowed a good outcome. The aim...

  19. Course of Encephalopathy in a Cirrhotic Dialysis Patient Treated Sequentially with Peritoneal and Hemodialysis

    Directory of Open Access Journals (Sweden)

    Suleyman Koz

    2015-01-01

    Full Text Available End-stage kidney disease and advanced cirrhosis are sometimes seen concomitantly. There is no consensus on dialysis modality in terms of determining the optimal way of treating these patients. It has been suggested that peritoneal dialysis is a better choice for these patients, but efficacy of hemodialysis in stable cirrhotic patients has not been evaluated sufficiently. We report a case with advanced cirrhosis and end-stage kidney disease who was faced with hepatic encephalopathy episodes up on starting renal replacement therapy. The case is also interesting in that it reveals effects of hemodialysis and peritoneal dialysis on hepatic encephalopathy episodes and quality of life of the patient.

  20. Hormone-dependence of sarin lethality in rats: Sex differences and stage of the estrous cycle

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Carl D., E-mail: carl.d.smith179.mil@mail.mil; Wright, Linnzi K.M.; Garcia, Gregory E.; Lee, Robyn B.; Lumley, Lucille A.

    2015-09-15

    Chemical warfare nerve agents (CWNAs) are highly toxic compounds that cause a cascade of symptoms and death, if exposed casualties are left untreated. Numerous rodent models have investigated the toxicity and mechanisms of toxicity of CWNAs, but most are limited to male subjects. Given the profound physiological effects of circulating gonadal hormones in female rodents, it is possible that the daily cyclical fluctuations of these hormones affect females' sensitivity to the lethal effects of CWNAs, and previous reports that included female subjects did not control for the stage of the hormonal cycle. The aim of the current study was to determine the 24-hour median lethal dose (LD{sub 50}) of the CWNA sarin in male, ovariectomized (OVEX) female, and female rats during different stages of the estrous cycle (diestrus, proestrus, and estrus). Additionally, baseline activity levels of plasma acetylcholinesterase, butyrylcholinesterase, and carboxylesterase were measured to determine differences among the groups. Results indicated that females in proestrus had a significantly higher LD{sub 50} of sarin compared to OVEX and estrous females. Although some sex differences were observed in the activity levels of plasma esterases, they were not consistent and likely not large enough to significantly affect the LD{sub 50}s. These results suggest that hormonal cyclicity can influence the outcome of CWNA-related studies using female rodents, and that this variability can be minimized by controlling for the stage of the cycle. Additional research is necessary to determine the precise mechanism of the observed differences because it is unlikely to be solely explained by plasma esterase activity. - Highlights: • The LD{sub 50} of sarin was determined in female rats throughout the stages of the estrous cycle. • Females in proestrus had a significantly higher LD{sub 50} compared to estrous or ovariectomized females. • No sex differences were observed between male and female

  1. Hormone-dependence of sarin lethality in rats: Sex differences and stage of the estrous cycle

    International Nuclear Information System (INIS)

    Chemical warfare nerve agents (CWNAs) are highly toxic compounds that cause a cascade of symptoms and death, if exposed casualties are left untreated. Numerous rodent models have investigated the toxicity and mechanisms of toxicity of CWNAs, but most are limited to male subjects. Given the profound physiological effects of circulating gonadal hormones in female rodents, it is possible that the daily cyclical fluctuations of these hormones affect females' sensitivity to the lethal effects of CWNAs, and previous reports that included female subjects did not control for the stage of the hormonal cycle. The aim of the current study was to determine the 24-hour median lethal dose (LD50) of the CWNA sarin in male, ovariectomized (OVEX) female, and female rats during different stages of the estrous cycle (diestrus, proestrus, and estrus). Additionally, baseline activity levels of plasma acetylcholinesterase, butyrylcholinesterase, and carboxylesterase were measured to determine differences among the groups. Results indicated that females in proestrus had a significantly higher LD50 of sarin compared to OVEX and estrous females. Although some sex differences were observed in the activity levels of plasma esterases, they were not consistent and likely not large enough to significantly affect the LD50s. These results suggest that hormonal cyclicity can influence the outcome of CWNA-related studies using female rodents, and that this variability can be minimized by controlling for the stage of the cycle. Additional research is necessary to determine the precise mechanism of the observed differences because it is unlikely to be solely explained by plasma esterase activity. - Highlights: • The LD50 of sarin was determined in female rats throughout the stages of the estrous cycle. • Females in proestrus had a significantly higher LD50 compared to estrous or ovariectomized females. • No sex differences were observed between male and female rats. • It is unlikely that

  2. Time dependent effects of Adriamycin and x-ray therapy on wound healing in the rat

    International Nuclear Information System (INIS)

    Wound healing as measured by wound breaking strength (WBS) was studied in male Fischer rats. Animals were wounded (day 0) and treated with Adriamycin (ADR), x-ray therapy (XRT), or the combination of ADR + XRT. Treatments were either on day -7,0 or +7. Animals were killed on days +14 and +21, and excised wounds were subjected to uniaxial extension and the recording of WBS (grams), hydroxy-proline assay, and collagen fiber diameter measurements. In this model, day 0 treatment with ADR, XRT, or ADR + XRT impaired WBS most significantly. This was supported by a diminution in newly synthesized hydroxyproline and load extension curve analysis

  3. Evidence for novel age-dependent network structures as a putative primo vascular network in the dura mater of the rat brain

    Institute of Scientific and Technical Information of China (English)

    Ho-Sung Lee; Dai-In Kang; Seung Zhoo Yoon; Yeon Hee Ryu; Inhyung Lee; Hoon-Gi Kim; Byung-Cheon Lee; Ki Bog Lee

    2015-01-01

    With chromium-hematoxylin staining, we found evidence for the existence of novel age-depen-dent network structures in the dura mater of rat brains. Under stereomicroscopy, we noticed that chromium-hematoxylin-stained threadlike structures, which were barely observable in 1-week-old rats, were networked in specific areas of the brain, for example, the lateral lobes and the cerebella, in 4-week-old rats. In 7-week-old rats, those structures were found to have become larger and better networked. With phase contrast microscopy, we found that in 1-week-old rats, chromium-hematoxylin-stained granules were scattered in the same areas of the brain in which the network structures would later be observed in the 4- and 7-week-old rats. Such age-depen-dent network structures were examined by using optical and transmission electron microscopy, and the following results were obtained. The scattered granules fused into networks with increas-ing age. Cross-sections of the age-dependent network structures demonstrated heavily-stained basophilic substructures. Transmission electron microscopy revealed the basophilic substructures to be clusters with high electron densities consisting of nanosized particles. We report these data as evidence for the existence of age-dependent network structures in the dura mater, we discuss their putative functions of age-dependent network structures beyond the general concept of the dura mater as a supporting matrix.

  4. EFFECTS OF HEMOGLOBIN ON SERUM NITRIC OXIDECONCENTRATION AND HEMODYNAMICS PATTERN CHANGES IN CIRRHOTIC RATS

    Institute of Scientific and Technical Information of China (English)

    黄颖秋; 萧树东; 莫剑忠; 张德中

    2000-01-01

    R6sumeobjectifPouretudierlYljtdelXemoglobineop)surleniveaudbxidenitriqueserique(NOetlacourbehemodynamiquechezlesratscirrhotiques.MdthodcsLesratscirrhotiquessontinjectdsparvoiehyPodermiqued,drythroPoitrtine(1ooU/kg)pendant2semaines,tensionart4riellemoyenneouP),debitcardiaque(CO),indicecardiaque(CI),resistancevasculairesPlanchnique(SVR,courantsanguinsPlanchnique(SBF)etconcentrationseriquedeNOetaientmesureschezlesratstraites,non-traitesetdescontr6les.RdsuItatsChezlesratsnon-traites,ilyaunediminutiondevaleurdeM...

  5. Balloon occlusion retrograde transvenous obliteration of gastric varices in two-cirrhotic patients with portal vein thrombosis

    Energy Technology Data Exchange (ETDEWEB)

    Borhei, Peyman; Kim, Seung Kwon; Zukerman, Darryl A [Interventional Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (United States)

    2014-02-15

    This report describes two non-cirrhotic patients with portal vein thrombosis who underwent successful balloon occlusion retrograde transvenous obliteration (BRTO) of gastric varices with a satisfactory response and no complications. One patient was a 35-year-old female with a history of Crohn's disease, status post-total abdominal colectomy, and portal vein and mesenteric vein thrombosis. The other patient was a 51-year-old female with necrotizing pancreatitis, portal vein thrombosis, and gastric varices. The BRTO procedure was a useful treatment for gastric varices in non-cirrhotic patients with portal vein thrombosis in the presence of a gastrorenal shunt.

  6. Portal venous blood flow while breath-holding after inspiration or expiration and during normal respiration in controls and cirrhotics

    Energy Technology Data Exchange (ETDEWEB)

    Sugano, Shigeo; Yamamoto, Kunihiro; Sasao, Ken-ichiro; Watanabe, Manabu [Saiseikai Wakakusa Hospital, Yakohama (Japan)

    1999-07-01

    In this study, we used magnetic resonance (MR) imaging to measure portal blood flow in 12 healthy controls and 17 cirrhotics while they were breath-holding after inspiration and after expiration. We then compared the results with measurements made during normal respiration in the healthy controls and cirrhotics. Blood flow in the main portal vein under basal fasting conditions was quantitated using the cine phase-contrast MR velocity mapping method. Three measurements were made on one occasion, as follows: throughout the cardiac cycle during normal respiration, with the subject breath-holding after maximal inspiration, and with the subject breath-holding after maximal expiration. During normal respiration, portal blood flow was 1.3{+-}0.2 l/min in controls vs 1.0{+-}0.1 l/min in cirrhotics (P<0.0001); while subjects were breath-holding after inspiration, portal blood flow was 1.0{+-}0.2 l/min in controls vs 0.9{+-}0.1 l/min in cirrhotics; and while subjects were breath-holding after expiration, portal blood flow was 1.5{+-}0.2 l/min in controls vs 1.1{+-}0.2 l/min in cirrhotics (P<0.0001). The differences were primarily due to changes in flow velocity. When the magnitude of these hemodynamic changes in the three respiratory conditions was compared in controls and cirrhotics, analysis of variance (ANOVA) showed a significant difference (P<0.0001). In controls, portal blood flow decreased during maximal inspiration relative to flow during normal respiration (-24.6{+-}8.3%). Changes in portal blood flow in controls were greater than in cirrhotics (-13.5{+-}4.5%) (P<0.0001); however, the difference in blood flow increase associated with maximal expiration between the two groups (+11.8{+-}9.4% vs +5.9{+-}11.5%) was not significant. We found that the respiration-induced hemodynamic variation in portal blood flow was less in cirrhotics than in the healthy controls. Portal blood flow measurements made during normal respiration using MR imaging closely reflect nearly

  7. Portal venous blood flow while breath-holding after inspiration or expiration and during normal respiration in controls and cirrhotics

    International Nuclear Information System (INIS)

    In this study, we used magnetic resonance (MR) imaging to measure portal blood flow in 12 healthy controls and 17 cirrhotics while they were breath-holding after inspiration and after expiration. We then compared the results with measurements made during normal respiration in the healthy controls and cirrhotics. Blood flow in the main portal vein under basal fasting conditions was quantitated using the cine phase-contrast MR velocity mapping method. Three measurements were made on one occasion, as follows: throughout the cardiac cycle during normal respiration, with the subject breath-holding after maximal inspiration, and with the subject breath-holding after maximal expiration. During normal respiration, portal blood flow was 1.3±0.2 l/min in controls vs 1.0±0.1 l/min in cirrhotics (P<0.0001); while subjects were breath-holding after inspiration, portal blood flow was 1.0±0.2 l/min in controls vs 0.9±0.1 l/min in cirrhotics; and while subjects were breath-holding after expiration, portal blood flow was 1.5±0.2 l/min in controls vs 1.1±0.2 l/min in cirrhotics (P<0.0001). The differences were primarily due to changes in flow velocity. When the magnitude of these hemodynamic changes in the three respiratory conditions was compared in controls and cirrhotics, analysis of variance (ANOVA) showed a significant difference (P<0.0001). In controls, portal blood flow decreased during maximal inspiration relative to flow during normal respiration (-24.6±8.3%). Changes in portal blood flow in controls were greater than in cirrhotics (-13.5±4.5%) (P<0.0001); however, the difference in blood flow increase associated with maximal expiration between the two groups (+11.8±9.4% vs +5.9±11.5%) was not significant. We found that the respiration-induced hemodynamic variation in portal blood flow was less in cirrhotics than in the healthy controls. Portal blood flow measurements made during normal respiration using MR imaging closely reflect nearly physiologic conditions

  8. Endomicroscopic analysis of time- and pressure-dependent area of subpleural alveoli in mechanically ventilated rats.

    Science.gov (United States)

    Runck, Hanna; Schwenninger, David; Haberstroh, Jörg; Guttmann, Josef

    2014-11-01

    We investigated the effects of recruitment maneuvers on subpleural alveolar area in healthy rats. 36 mechanically ventilated rats were allocated to either ZEEP-group or PEEP - 5cmH2O - group. The subpleural alveoli were observed using a transthoracal endoscopic imaging technique. Two consecutive low-flow maneuvers up to 30cmH2O peak pressure each were performed, interrupted by 5s plateau phases at four different pressure levels. Alveolar area change at maneuver peak pressures and during the plateau phases was calculated and respiratory system compliance before and after the maneuvers was analyzed. In both groups alveolar area at the second peak of the maneuver did not differ significantly compared to the first peak. During the plateau phases there was a slight increase in alveolar area. After the maneuvers, compliance increased by 30% in ZEEP group and 20% in PEEP group. We conclude that the volume insufflated by the low-flow recruitment maneuver is distributed to deeper but not to subpleural lung regions. PMID:25150503

  9. Hormone-dependent aggression in male rats is proportional to serum testosterone concentration but sexual behavior is not.

    Science.gov (United States)

    Albert, D J; Jonik, R H; Watson, N V; Gorzalka, B B; Walsh, M L

    1990-09-01

    Male hooded rats were castrated and implanted with Silastic capsules (1.57 mm i.d.; 3.18 mm o.d.) having a testosterone-filled space 0, 7, 22, 60, or 90 mm long. All animals were returned to their original group cages for a three-week period to allow hormone concentrations and behavioral tendencies to stabilize. Each male was then housed with an intact female in a large cage. Aggression by the male toward an unfamiliar male was tested at weekly intervals for three weeks. Sexual behavior with an estrogen/progesterone-primed ovariectomized female was tested on each of the subsequent two weeks. Serum testosterone was measured during the following week. The frequency of aggression was correlated with serum testosterone concentration up to the normal level and did not increase with higher serum testosterone concentrations. In contrast, sexual behavior was virtually absent in animals with no testosterone replacement and normal in all other groups. These results demonstrate a clear dissociation in the dependence of hormone-dependent aggression and sexual behavior on serum testosterone concentration. In a male cohabiting with a female, sexual experience activates hormone-dependent aggression toward an unfamiliar male but the level of aggression that develops depends on the serum testosterone concentration in the resident male.

  10. Dose-dependent effects of procyanidin on nerve growth factor expression following cerebral ischemia/ reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Feng Li; Hai Xie; Ying Gao; Tongxia Zhan

    2008-01-01

    BACKGROUND: Recently, grape seed procyanidin (GSP) has been shown to be exhibit antioxidant effects, effectively reducing ischemia/reperfusion injury and inhibiting brain cell apoptosis.OBJECTIVE: To study the effects of GSP on nerve growth factor (NGF) expression and neurological function following cerebral ischemia/reperfusion injury in rats.DESIGN: Randomized controlled study based on SD rats.SETTING: Weifang Municipal People's Hospital. MATERIALS: Forty-eight healthy adult SD rats weighing 280-330 g and irrespective of gender were provided by the Experimental Animal Center of Shandong University. GSP derived from grape seed was a new high-effective antioxidant provided by Tianjin Jianfeng Natural Product Researching Company (batch number: 20060107). Rabbit-anti-rat NGF monoclonal antibody was provided by Beijing Zhongshan Biotechnology Co., Ltd., and SABC immunohistochemical staining kit by Wuhan Boster Bioengineering Co., Ltd. METHODS: The present study was performed in the Functional Laboratory of Weifang Medical College from April 2006 to January 2007. Forty-eight SD rats were randomly divided into the sham operation group, ischemia/reperfusion group, high-dose GSP (40 mg/kg) group, or low-dose GSP (10 mg/kg) group (n = 12 per group). Ischemia/reperfusion injury was established using the threading embolism method of the middle cerebral artery. Rats in the ischemia/reperfusion model group were given saline injection (2 mL/kg i.p.) once daily for seven days pre-ischemia/reperfusion, and once more at 15 minutes before reperfusion. Rats in the high-dose and low-dose GSP groups were injected with GSP (20 or 5 mg/mL i.p., respectively, 2 mL/kg) with the same regime as the ischemia/reperfusion model group. The surgical procedures in the sham operation group were as the same as those in the ischemia/reperfusion model group, but the thread was approximately 10 mm long, thus, the middle cerebral artery was not blocked. MAIN OUTCOME MEASURES: NGF expression in the

  11. Inhibition of PKC-dependent extracellular Ca2+ entry contributes to the depression of contractile activity in long-term pressure-overloaded endothelium-denuded rat aortas

    International Nuclear Information System (INIS)

    We examined the contractile responsiveness of rat thoracic aortas under pressure overload after long-term suprarenal abdominal aortic coarctation (lt-Srac). Endothelium-dependent angiotensin II (ANG II) type 2 receptor (AT2R)-mediated depression of contractions to ANG II has been reported in short-term (1 week) pressure-overloaded rat aortas. Contractility was evaluated in the aortic rings of rats subjected to lt-Srac or sham surgery (Sham) for 8 weeks. ANG I and II levels and AT2R protein expression in the aortas of lt-Srac and Sham rats were also evaluated. lt-Srac attenuated the contractions of ANG II and phenylephrine in the aortas in an endothelium-independent manner. However, lt-Srac did not influence the transient contractions induced in endothelium-denuded aortic rings by ANG II, phenylephrine, or caffeine in Ca2+-free medium or the subsequent tonic constrictions induced by the addition of Ca2+ in the absence of agonists. Thus, the contractions induced by Ca2+ release from intracellular stores and Ca2+ influx through stored-operated channels were not inhibited in the aortas of lt-Srac rats. Potassium-elicited contractions in endothelium-denuded aortic rings of lt-Srac rats remained unaltered compared with control tissues. Consequently, the contractile depression observed in aortic tissues of lt-Srac rats cannot be explained by direct inhibition of voltage-operated Ca2+ channels. Interestingly, 12-O-tetradecanoylphorbol-13-acetate-induced contractions in endothelium-denuded aortic rings of lt-Srac rats were depressed in the presence but not in the absence of extracellular Ca2+. Neither levels of angiotensins nor of AT2R were modified in the aortas after lt-Srac. The results suggest that, in rat thoracic aortas, lt-Srac selectively inhibited protein kinase C-mediated activation of contraction that is dependent on extracellular Ca2+ entry

  12. Lifelong elimination of hyperbilirubinemia in the Gunn rat with a single injection of helper-dependent adenoviral vector.

    Science.gov (United States)

    Toietta, Gabriele; Mane, Viraj P; Norona, Wilma S; Finegold, Milton J; Ng, Philip; McDonagh, Antony F; Beaudet, Arthur L; Lee, Brendan

    2005-03-15

    Crigler-Najjar syndrome is a recessively inherited disorder characterized by severe unconjugated hyperbilirubinemia caused by a deficiency of uridine diphospho-glucuronosyl transferase 1A1. Current therapy relies on phototherapy to prevent kernicterus, but liver transplantation presently is the only permanent cure. Gene therapy is a potential alternative, and recent work has shown that helper-dependent adenoviral (HD-Ad) vectors, devoid of all viral coding sequences, induce prolonged transgene expression and exhibit significantly less chronic toxicity than early-generation Ad vectors. We used a HD-Ad vector to achieve liver-restricted expression of human uridine diphospho-glucuronosyl transferase 1A1 in the Gunn rat, a model of the human disorder. Total plasma bilirubin levels were reduced from >5.0 mg/dl to 2 yr after a single i.v. administration of vector expressing the therapeutic transgene at a dose of 3 x 10(12) viral particles per kg. HPLC analysis of bile from treated rats showed the presence of bilirubin glucuronides at normal WT levels >2 yr after one injection of vector, and i.v. injection of bilirubins IIIalpha and XIIIalpha in the same animals revealed excess bilirubin-conjugating capacity. There was no significant elevation of liver enzymes (alanine aminotransferase) and only transient, moderate thrombocytopenia after injection of the vector. A clinically significant reduction in serum bilirubin was observed with a dose as low as 6 x 10(11) viral particles per kg. We conclude that complete, long-term correction of hyperbilirubinemia in the Gunn rat model of Crigler-Najjar syndrome can be achieved with one injection of HD-Ad vector and negligible chronic toxicity. PMID:15753292

  13. The changes in levels of C-P and insulin in glucose tolerance test in rats with experimental non-insulin dependent diabetes mellitus

    International Nuclear Information System (INIS)

    The changes in levels of C-P and insulin were investigated in the GT test in rats with non-insulin dependent diabetes mellitus. In order to establish a model of non-insulin dependent diabetes mellitus (NIDDM), the authors injected rats with small dose streptozocoi (i.v.). Two weeks after the injection, the rats developed impaired glucose tolerance (IGT). Then, they were fed with high energy diet for eight weeks to form NIDDM. The results showed that the highest peak time of C-P and insulin in NIDDM was remarkably later than that in normal subjects, the highest peak time was in two hours (P < 0.05). The data suggest that level of C-P could accurately respond to level of insulin, and this experimental non-insulin dependent diabetes mellitus model is ideal

  14. Time-Dependent Alterations in Rat Macrovessels with Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Yvonne Searls

    2012-01-01

    Full Text Available Vascular complications are associated with the progressive severity of diabetes, resulting in significant morbidity and mortality. This study quantifies functional vascular parameters and macrovascular structure in a rat model of type 1 diabetes. While there was no difference in the systemic arterial elastance (Ea with 50 days of diabetes, changes were noted in the aorta and femoral artery including increased tunica media extracellular matrix content, decreased width of both the media and individual smooth muscle cell layers, and increased incidence of damaged mitochondria. Extracellular matrix proteins and elastin levels were significantly greater in the aorta of diabetic animals. These differences correlated with diminished matrix metalloprotease activity in the aorta of the diabetic animals. In conclusion, diabetes significantly altered the structure and ultrastructure of the aorta and femoral artery before systemic changes in arterial elastance could be detected.

  15. Endothelium-Dependent Vasorelaxant Effect of Butanolic Fraction from Caryocar brasiliense Camb. Leaves in Rat Thoracic Aorta

    Directory of Open Access Journals (Sweden)

    Lais Moraes de Oliveira

    2012-01-01

    Full Text Available Caryocar brasiliense Camb. “pequi” is a native plant from the Cerrado region of Brazil that contains bioactive components reported to be antioxidant agents. Previous work has demonstrated that dietary supplementation with pequi decreased the arterial pressure of volunteer athletes. We found that the crude hydroalcoholic extract (CHE of C. brasiliense leaves relaxed, in a concentration-dependent manner, rat aortic rings precontracted with phenylephrine, and that the butanolic fraction (BF produced an effect similar to that of the CHE. Aortic relaxation induced by BF was abolished by endothelium removal, by incubation of the nitric oxide synthase inhibitor L-NAME, or the soluble guanylatecyclase inhibitor ODQ. However, incubation with atropine and pyrilamine had no effect on the BF-induced vasorelaxation. Moreover, this effect was not inhibited by indomethacin and tetraethylammonium. The concentration-response curve to calcium in denuded-endothelium rings was not modified after incubation with BF, and the vasorelaxation by BF in endothelium-intact rings precontracted with KCl was abolished after incubation with L-NAME. In addition, administration of BF in anesthetized rats resulted in a reversible hypotension. The results reveal that C. brasiliense possesses both in vivo and in vitro activities and that the vascular effect of BF involves stimulation of the nitric oxide/cyclic GMP pathway.

  16. Protective effect of vitamin E on cypermethrin-induced follicular atresia in rat ovary: Evidence for energy dependent mechanism.

    Science.gov (United States)

    Molavi, Morteza; Razi, Mazdak; Cheraghi, Hadi; Khorramjouy, Mona; Ostadi, Araz; Gholirad, Safa

    2016-01-01

    It has been shown that chronic exposure to cypermethrin (CPM), a pyrethroid pesticide, results in follicular atresia via pathologically affecting angiogenesis, disrupting endocrine potential and enhancing oxidative stress. This study was aimed to uncover the CPM-exposed energy dependent follicular cells apoptosis and to estimate protective effect of vitamin E (VitE) as a potent antioxidant. Thirty six Wistar rats were divided into six groups (n = 6 rats for each group) including; control-sham, CPM-received (CPM, 75 mg kg(-1), intraperitoneally), and CPM and VitE-treated (VitE, 150 mg kg(-1), orally) for 14 and 24 days. The protein biosynthesis of glucose transporter-1 (GLUT-1) and caspase-3 in follicles were estimated by using immuno-histochemical staining at preantral and antral stages. Moreover, the periodic acid Schiff (PAS) staining was performed in order to evaluate the intracytoplasmic carbohydrate ratio in follicular cells and oocyte. Percentages of follicles with GLUT-1, Caspase-3 and PAS-positive cells were compared between groups. Immunohistochemical analyses showed that, VitE significantly up-regulated the GLUT-1 expression and improved the intracytoplasmic carbohydrate supplementation especially at preantral follicles. The cross sections from the CPM-exposed ovaries represented remarkable elevation in percentage of atretic preantral and antral follicles with caspase-3 biosynthesis, which was remarkably (p glucose uptake at follicular cells and oocyte levels that in turn inhibited pro-apoptotic protein caspase-3 biosynthesis. PMID:27482357

  17. Structural and functional cerebral impairments in cirrhotic patients with a history of overt hepatic encephalopathy

    International Nuclear Information System (INIS)

    Objective: Diffuse brain atrophy has been observed in cirrhotic patients and recent reports have revealed the persistence of cognitive impairment after clinical resolution of overt hepatic encephalopathy. We sought to explore the continued influence of overt hepatic encephalopathy on neurological function by measuring brain resting-state inherent connectivity, based on an investigation of structural abnormalities. Methods: Neuropsychological tests and structural and functional magnetic resonance scanning were conducted in 20 healthy controls and 21 cirrhotic patients with a history of overt hepatic encephalopathy. The analysis of voxel-based morphometry and functional connectivity were performed to detect the alterations in brain structure and function, respectively. Results: Patients showed significantly worse performance in neuropsychological tests as compared with controls, despite apparently normal mental status. Analysis of voxel-based morphometry revealed a decrease in gray matter volume primarily in the midline regions, bilateral insular cortex and caudates, left parahippocampal gyrus, and right cerebellum posterior lobe, while the volume of the bilateral thalamus showed an increase. Of these regions, the posterior cingulate cortex with peak atrophy was selected as the origin for the analysis of functional connectivity. Typical patterns of a default mode network were identified in both groups. Decreased functional connectivity was found in the medial prefrontal gyrus, left inferior parietal lobule, and left middle temporal gyrus in the patients. Conclusions: Both functional and structural impairments were evident after apparent recovery from overt hepatic encephalopathy, demonstrating that brain dysfunction induced by hepatic encephalopathy persisted after clinical resolution and provided a basis for further evolution of the disease

  18. Hepatocyte differentiation of human fibroblasts from cirrhotic liver in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Yu-Ling Sun; Sheng-Yong Yin; Lin Zhou; Hai-Yang Xie; Feng Zhang; Li-Ming Wu; Shu-Sen Zheng

    2011-01-01

    BACKGROUND: Mesenchymal stem cells (MSCs) and fibro-blasts have intimate relationships, and the phenotypic homology between fibroblasts and MSCs has been recently described. The aim of this study was to investigate the hepatic differentiating potentialofhumanfibroblastsincirrhoticliver. METHODS: The phenotypes of fibroblasts in cirrhotic liver were labeled by biological methods. After that, the differentiation potential of these fibroblasts in vitro was characterized in terms of liver-specific gene and protein expression. Finally, an animal model of hepatocyte regeneration in severe combined immunodeficient (SCID) mice was created by retrorsine injection and partial hepatectomy, and the expression of human hepatocyte proteins in SCID mouse livers was checked by immunohistochemicalanalysisafterfibroblastadministration. RESULTS: Surface immunophenotyping revealed that a minority of fibroblasts expressed markers of MSCs and hepatic epithelial cytokeratins as well as alpha-smooth muscle actin, but homogeneously expressed vimentin, desmin, prolyl 4-hydroxylase and fibronectin. These fibroblasts presented the characteristics of hepatocytes in vitro and differentiated directly into functional hepatocytes in the liver of hepatecto-mized SCID mice. CONCLUSIONS: This study demonstrated that fibroblasts in cirrhotic liver have the potential to differentiate into hepatocyte-like cells in vitro and in vivo. Our findings infer that hepatic differentiation of fibroblasts may serve as a new target for reversion of liver fibrosis and a cell source for tissue engineering.

  19. Structural and functional cerebral impairments in cirrhotic patients with a history of overt hepatic encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Hua-Jun [Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009 (China); Zhu, Xi-Qi [Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009 (China); Department of Radiology, The Second Hospital of Nanjing, Medical School of Southeast University, Nanjing 210002 (China); Shu, Hao [Department of Neurology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009 (China); Yang, Ming; Zhang, Yi; Ding, Jie; Wang, Yu [Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009 (China); Teng, Gao-Jun, E-mail: gjteng@vip.sina.com [Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009 (China)

    2012-10-15

    Objective: Diffuse brain atrophy has been observed in cirrhotic patients and recent reports have revealed the persistence of cognitive impairment after clinical resolution of overt hepatic encephalopathy. We sought to explore the continued influence of overt hepatic encephalopathy on neurological function by measuring brain resting-state inherent connectivity, based on an investigation of structural abnormalities. Methods: Neuropsychological tests and structural and functional magnetic resonance scanning were conducted in 20 healthy controls and 21 cirrhotic patients with a history of overt hepatic encephalopathy. The analysis of voxel-based morphometry and functional connectivity were performed to detect the alterations in brain structure and function, respectively. Results: Patients showed significantly worse performance in neuropsychological tests as compared with controls, despite apparently normal mental status. Analysis of voxel-based morphometry revealed a decrease in gray matter volume primarily in the midline regions, bilateral insular cortex and caudates, left parahippocampal gyrus, and right cerebellum posterior lobe, while the volume of the bilateral thalamus showed an increase. Of these regions, the posterior cingulate cortex with peak atrophy was selected as the origin for the analysis of functional connectivity. Typical patterns of a default mode network were identified in both groups. Decreased functional connectivity was found in the medial prefrontal gyrus, left inferior parietal lobule, and left middle temporal gyrus in the patients. Conclusions: Both functional and structural impairments were evident after apparent recovery from overt hepatic encephalopathy, demonstrating that brain dysfunction induced by hepatic encephalopathy persisted after clinical resolution and provided a basis for further evolution of the disease.

  20. Hepatocellular carcinoma in cirrhotic patients: prospective comparison of US, CT and MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Di Martino, Michele; De Filippis, Gianmaria; Geiger, Daniel; Del Monte, Maurizio; Lombardo, Concetta Valentina; Catalano, Carlo [University of Rome ' ' Sapienza' ' , Department of Radiological Sciences, Oncology and Anatomical Pathology, Rome (Italy); De Santis, Adriano; Corradini, Stefano Ginanni [University of Rome ' ' Sapienza' ' , Department of Clinical Medicine, Division of Gastroenterology, Rome (Italy); Rossi, Massimo; Mennini, Gianluca [University of Rome ' ' Sapienza' ' , Department of General Surgery, Division of Organ Transplantation, Rome (Italy)

    2013-04-15

    To prospectively compare the diagnostic performance of ultrasound (US), multidetector computed tomography (MDCT) and contrast-enhanced magnetic resonance imaging (MRI) in cirrhotic patients who were candidates for liver transplantation. One hundred and forty consecutive patients with 163 hepatocellular carcinoma (HCC) nodules underwent US, MRI and MDCT. Diagnosis of HCC was based on pathological findings or substantial growth at 12-month follow-up. Four different image datasets were evaluated: US, MDCT, MRI unenhanced and dynamic phases, MRI unenhanced dynamic and hepatobiliary phase. Diagnostic accuracy, sensitivity, specificity, PPV and NPV, with corresponding 95 % confidence intervals, were determined. Statistical analysis was performed for all lesions and for three lesion subgroups (<1 cm, 1-2 cm, >2 cm). Significantly higher diagnostic accuracy, sensitivity and NPV was achieved on dynamic + hepatobiliary phase MRI compared with US, MDCT and dynamic phase MRI alone. The specificity and PPV of US was significantly lower than that of MDCT, dynamic phase MRI and dynamic + hepatobiliary phase MRI. Similar results were obtained for all sub-group analyses, with particular benefit for the diagnosis of smaller lesions between 1 and 2 cm. Dynamic + hepatobiliary phase MRI improved detection and characterisation of HCC in cirrhotic patients. The greatest benefit is for diagnosing lesions between 1 and 2 cm. (orig.)

  1. Sex-Dependent Changes in Striatal Dopamine Transport in Preadolescent Rats Exposed Prenatally and/or Postnatally to Methamphetamine.

    Science.gov (United States)

    Sirova, Jana; Kristofikova, Zdenka; Vrajova, Monika; Fujakova-Lipski, Michaela; Ripova, Daniela; Klaschka, Jan; Slamberova, Romana

    2016-08-01

    Methamphetamine (MA) is the most commonly used psychostimulant drug, the chronic abuse of which leads to neurodegenerative changes in the brain. The global use of MA is increasing, including in pregnant women. Since MA can cross both placental and haematoencephalic barriers and is also present in maternal milk, children of chronically abused mothers are exposed prenatally as well as postnatally. Women seem to be more vulnerable to some aspects of MA abuse than men. MA is thought to exert its effects among others via direct interactions with dopamine transporters (DATs) in the brain tissue. Sexual dimorphism of the DAT system could be a base of sex-dependent actions of MA observed in behavioural and neurochemical studies. Possible sex differences in the DATs of preadolescent offspring exposed to MA prenatally and/or postnatally have not yet been evaluated. We examined the striatal synaptosomal DATs (the activity and density of surface expressed DATs and total DAT expression) in preadolescent male and female Wistar rats (31-35-day old animals) exposed prenatally and/or postnatally to MA (daily 5 mg/kg, s.c. to mothers during pregnancy and lactation). To distinguish between specific and nonspecific effects of MA on DATs, we also evaluated the in vitro effects of lipophilic MA on the fluidity of striatal membranes isolated from preadolescent and young adult rats of both sexes. We observed similar changes in the DATs of preadolescent rats exposed prenatally or postnatally (MA-mediated drop in the reserve pool but no alterations in surface-expressed DATs). However, prenatal exposure evoked significant changes in males and postnatal exposure in females. A significant decrease in the activity of surface-expressed DATs was found only in postnatally exposed females sensitized to MA via prenatal exposure. MA applied in vitro increased the fluidity of striatal membranes of preadolescent female but not male rats. In summary, DATs of preadolescent males are more sensitive to

  2. Co-administration of morphine and gabapentin leads to dose dependent synergistic effects in a rat model of postoperative pain

    DEFF Research Database (Denmark)

    Papathanasiou, Theodoros; Juul, Rasmus Vestergaard; Heegaard, Anne-Marie;

    2016-01-01

    Despite much evidence that combination of morphine and gabapentin can be beneficial for managing postoperative pain, the nature of the pharmacological interaction of the two drugs remains unclear. The aim of this study was to assess the interaction of morphine and gabapentin in range of different...... dose combinations and investigate whether co-administration leads to synergistic effects in a preclinical model of postoperative pain. The pharmacodynamic effects of morphine (1, 3 and 7 mg/kg), gabapentin (10, 30 and 100 mg/kg) or their combination (9 combinations in total) were evaluated in the rat...... surface analyses. The combination of morphine and gabapentin resulted in synergistic antihyperalgesic effects in a preclinical model of postoperative pain. The synergistic interactions were found to be dose dependent and the increase in observed response compared to the theoretical additive response...

  3. Contribution to the penetration of radionuclides across the skin. Age dependence of promethium through rat skin in vitro

    International Nuclear Information System (INIS)

    In this paper: - the time dependence of permeation of 147Pm3+ from aqueous solution through animal skin model was studied; - the age dependence of promethium through the skin was proved; - the optimum biological model of human skin was selected, and - the relative importance of the main diffusion pathways for 147Pm3+ the diffusion across the intact skin and the diffusion through the hair channels was assessed. Concluding it can be said, that: -it was proved, that the 5-day-old rats (5DR) represents the optimum animal model to the human skin; - in the case of 8DR to 11DR the dominant route of 147Pm3+ penetration is along the follicles; - the permeation resistance of the skin depends on the thickness and mechanical properties of the skin. Comparing amounts of penetrated ions of promethium through the skin without hairs (3DR to 6DR) and through the skin with hairs, it was showed that the additional diffusion along hair's follicles pronounced with animal skin can be important also in case of human skin where hair density is many times lower than in used animal models. (authors)

  4. Distinct target cell-dependent forms of short-term plasticity of the central visceral afferent synapses of the rat

    Directory of Open Access Journals (Sweden)

    Watabe Ayako M

    2010-10-01

    Full Text Available Abstract Background The visceral afferents from various cervico-abdominal sensory receptors project to the dorsal vagal complex (DVC, which is composed of the nucleus of the solitary tract (NTS, the area postrema and the dorsal motor nucleus of the vagus nerve (DMX, via the vagus and glossopharyngeal nerves and then the solitary tract (TS in the brainstem. While the excitatory transmission at the TS-NTS synapses shows strong frequency-dependent suppression in response to repeated stimulation of the afferents, the frequency dependence and short-term plasticity at the TS-DMX synapses, which also transmit monosynaptic information from the visceral afferents to the DVC neurons, remain largely unknown. Results Recording of the EPSCs activated by paired or repeated TS stimulation in the brainstem slices of rats revealed that, unlike NTS neurons whose paired-pulse ratio (PPR is consistently below 0.6, the distribution of the PPR of DMX neurons shows bimodal peaks that are composed of type I (PPR, 0.6-1.5; 53% of 120 neurons recorded and type II (PPR, Conclusions These two general types of short-term plasticity might contribute to the differential activation of distinct vago-vagal reflex circuits, depending on the firing frequency and type of visceral afferents.

  5. Activation of purinergic receptors (P2) in the renal medulla promotes endothelin-dependent natriuresis in male rats.

    Science.gov (United States)

    Gohar, Eman Y; Speed, Joshua S; Kasztan, Malgorzata; Jin, Chunhua; Pollock, David M

    2016-08-01

    Renal endothelin-1 (ET-1) and purinergic signaling systems regulate Na(+) reabsorption in the renal medulla. A link between the renal ET-1 and purinergic systems was demonstrated in vitro, however, the in vivo interaction between these systems has not been defined. To test whether renal medullary activation of purinergic (P2) receptors promotes ET-dependent natriuresis, we determined the effect of increased medullary NaCl loading on Na(+) excretion and inner medullary ET-1 mRNA expression in anesthetized adult male Sprague-Dawley rats in the presence and absence of purinergic receptor antagonism. Isosmotic saline (NaCl; 284 mosmol/kgH2O) was infused into the medullary interstitium (500 μl/h) during a 30-min baseline urine collection period, followed by isosmotic or hyperosmotic saline (1,800 mosmol/kgH2O) for two further 30-min urine collection periods. Na(+) excretion was significantly increased during intramedullary infusion of hyperosmotic saline. Compared with isosmotic saline, hyperosmotic saline infused into the renal medulla caused significant increases in inner medullary ET-1 mRNA expression. Renal intramedullary infusion of the P2 receptor antagonist suramin inhibited the increase in Na(+) excretion and inner medullary ET-1 mRNA expression induced by NaCl loading in the renal medulla. Activation of medullary P2Y2/4 receptors by infusion of UTP increased urinary Na(+) excretion. Combined ETA and ETB receptor blockade abolished the natriuretic response to intramedullary infusion of UTP. These data demonstrate that activation of medullary P2 receptors promotes ET-dependent natriuresis in male rats, suggesting that the renal ET-1 and purinergic signaling systems interact to efficiently facilitate excretion of a NaCl load.

  6. Region-Dependent Role of Cell-Penetrating Peptides in Insulin Absorption Across the Rat Small Intestinal Membrane.

    Science.gov (United States)

    Khafagy, El-Sayed; Iwamae, Ruisha; Kamei, Noriyasu; Takeda-Morishita, Mariko

    2015-11-01

    We have reported that the cell-penetrating peptide (CPP) penetratin acts as a potential absorption enhancer in oral insulin delivery systems and that this action occurs through noncovalent intermolecular interactions. However, the region-dependent role of CPPs in intestinal insulin absorption has not been clarified. To identify the intestinal region where CPPs have the most effect in increasing insulin absorption, the region-dependent action of penetratin was investigated using in situ closed intestinal loops in rats. The order of the insulin area under the insulin concentration-time curve (AUC) increase effect by L-penetratin was ileum > jejunum > duodenum > colon. By contrast, the AUC order after coadministration of insulin with D-penetratin was colon > duodenum ≥ jejunum and ileum. We also compared the effects of the L- and D-forms of penetratin, R8, and PenetraMax on ileal insulin absorption. Along with the CPPs used in this study, L- and D-PenetraMax produced the largest insulin AUCs. An absorption study using ilea pretreated with CPPs showed that PenetraMax had no irreversible effect on the intestinal epithelial membrane. The degradation of insulin in the presence of CPPs was assessed in rat intestinal enzymatic fluid. The half-life (t 1/2) of insulin increased from 14.5 to 23.7 and 184.7 min in the presence of L- and D-PenetraMax, respectively. These enzymatic degradation-resistant effects might contribute partly to the increased ileal absorption of insulin induced by D-PenetraMax. In conclusion, this study demonstrated that the ability of the L- and D-forms of penetratin to increase intestinal insulin absorption was maximal in the ileum and the colon, respectively, and that D-PenetraMax is a powerful but transient enhancer of oral insulin absorption.

  7. Changes in Astroglial Markers in a Maternal Immune Activation Model of Schizophrenia in Wistar Rats are Dependent on Sex.

    Science.gov (United States)

    de Souza, Daniela F; Wartchow, Krista M; Lunardi, Paula S; Brolese, Giovana; Tortorelli, Lucas S; Batassini, Cristiane; Biasibetti, Regina; Gonçalves, Carlos-Alberto

    2015-01-01

    Data from epidemiological studies suggest that prenatal exposure to bacterial and viral infection is an important environmental risk factor for schizophrenia. The maternal immune activation (MIA) animal model is used to study how an insult directed at the maternal host can have adverse effects on the fetus, leading to behavioral and neurochemical changes later in life. We evaluated whether the administration of LPS to rat dams during late pregnancy affects astroglial markers (S100B and GFAP) of the offspring in later life. The frontal cortex and hippocampus were compared in male and female offspring on postnatal days (PND) 30 and 60. The S100B protein exhibited an age-dependent pattern of expression, being increased in the frontal cortex and hippocampus of the MIA group at PND 60, while at PND 30, male rats presented increased S100B levels only in the frontal cortex. Considering that S100B secretion is reduced by elevation of glutamate levels, we may hypothesize that this early increment in frontal cortex tissue of males is associated with elevated extracellular levels of glutamate and glutamatergic hypofunction, an alteration commonly associated with SCZ pathology. Moreover, we also found augmented GFAP in the frontal cortex of the LPS group at PND 30, but not in the hippocampus. Taken together data indicate that astroglial changes induced by MIA are dependent on sex and brain region and that these changes could reflect astroglial dysfunction. Such alterations may contribute to our understanding of the abnormal neuronal connectivity and developmental aspects of SCZ and other psychiatric disorders. PMID:26733814

  8. Changes in astroglial markers in a maternal immune activation model of schizophrenia in Wistar rats are dependent on sex

    Directory of Open Access Journals (Sweden)

    Daniela Fraga de Souza

    2015-12-01

    Full Text Available Data from epidemiological studies suggest that prenatal exposure to bacterial and viral infection is an important environmental risk factor for schizophrenia. The maternal immune activation (MIA animal model is used to study how an insult directed at the maternal host can have adverse effects on the fetus, leading to behavioral and neurochemical changes later in life. We evaluated whether the administration of LPS to rat dams during late pregnancy affects astroglial markers (S100B and GFAP of the offspring in later life. The frontal cortex and hippocampus were compared in male and female offspring on postnatal days (PND 30 and 60. The S100B protein exhibited an age-dependent pattern of expression, being increased in the frontal cortex and hippocampus of the MIA group at PND 60, while at PND 30, male rats presented increased S100B levels only in the frontal cortex. Considering that S100B secretion is reduced by elevation of glutamate levels, we may hypothesize that this early increment in frontal cortex tissue of males is associated with elevated extracellular levels of glutamate and glutamatergic hypofunction, an alteration commonly associated with SCZ pathology. Moreover, we also found augmented GFAP in the frontal cortex of the LPS group at PND 30, but not in the hippocampus. Taken together data indicate that astroglial changes induced by MIA are dependent on sex and brain region and that these changes could reflect astroglial dysfunction. Such alterations may contribute to our understanding of the abnormal neuronal connectivity and developmental aspects of SCZ and other psychiatric disorders.

  9. Temperature- and concentration-dependence of kainate-induced y oscillation in rat hippocampal slices under submerged condition

    Institute of Scientific and Technical Information of China (English)

    Cheng-biao LU; Zhi-hua WANG; Yan-hong ZHOU; Martin VREUGDENHIL

    2012-01-01

    Aim:Fast neuronal network oscillation at the y frequency band (y oscillation:30-80 Hz) has been studied extensively in hippocampal slices under interface recording condition.The aim of this study is to establish a method for recording Y oscillation in submerged hippocampal slices that allows simultaneously monitoring Y oscillation and the oscillation-related intracellular events,such as intracellular Ca2+ concentration or mitochondrial membrane potentials.Methods:Horizontal hippocampal slices (thickness:300 pm) of adult rats were prepared and placed in a submerged or an interface chamber.Extracellular field recordings Were made in the CA3c pyramidal layer of the slices.Kainate,an AMPA/kainate receptor agonist,was applied via perfusion.Data analysis was performed off-line.Results:Addition of kainate (25-1000 nmol/L) induced Y oscillation in both the submerged and interface slices.Kainate increased the Y power in a concentration-dependent manner,but the duration of steady state oscillation was reduced at higher concentrations of kainate.Long-lasting Y oscillation was maintained at the concentrations of 100-300 nmol/L.Under submerged condition,Y oscillation was temperature-dependent,with the maximum power achieved at 29℃.The induction of Y oscillation under submerged condition also required a fast rate of perfusion (5-7 mL/min) and showed a fast dynamic during development and after the washout.Conclusion:The kainite-induced Y oscillation recorded in submerged rat hippocampal slices is useful for studying the intracellular events related to neuronal network activities and may represent a model to reveal the mechanisms underlying the normal neuronal synchronizations and diseased conditions.

  10. Differential effects of ghrelin antagonists on alcohol drinking and reinforcement in mouse and rat models of alcohol dependence.

    Science.gov (United States)

    Gomez, Juan L; Cunningham, Christopher L; Finn, Deborah A; Young, Emily A; Helpenstell, Lily K; Schuette, Lindsey M; Fidler, Tara L; Kosten, Therese A; Ryabinin, Andrey E

    2015-10-01

    An effort has been mounted to understand the mechanisms of alcohol dependence in a way that may allow for greater efficacy in treatment. It has long been suggested that drugs of abuse seize fundamental reward pathways and disrupt homeostasis to produce compulsive drug seeking behaviors. Ghrelin, an endogenous hormone that affects hunger state and release of growth hormone, has been shown to increase alcohol intake following administration, while antagonists decrease intake. Using rodent models of dependence, the current study examined the effects of two ghrelin receptor antagonists, [DLys3]-GHRP-6 (DLys) and JMV2959, on dependence-induced alcohol self-administration. In two experiments adult male C57BL/6J mice and Wistar rats were made dependent via intermittent ethanol vapor exposure. In another experiment, adult male C57BL/6J mice were made dependent using the intragastric alcohol consumption (IGAC) procedure. Ghrelin receptor antagonists were given prior to voluntary ethanol drinking. Ghrelin antagonists reduced ethanol intake, preference, and operant self-administration of ethanol and sucrose across these models, but did not decrease food consumption in mice. In experiments 1 and 2, voluntary drinking was reduced by ghrelin receptor antagonists, however this reduction did not persist across days. Despite the transient effects of ghrelin antagonists, the drugs had renewed effectiveness following a break in administration as seen in experiment 1. The results show the ghrelin system as a potential target for studies of alcohol abuse. Further research is needed to determine the central mechanisms of these drugs and their influence on addiction in order to design effective pharmacotherapies.

  11. Eugenol dilates rat cerebral arteries by inhibiting smooth muscle cell voltage-dependent calcium channels.

    Science.gov (United States)

    Peixoto-Neves, Dieniffer; Leal-Cardoso, Jose Henrique; Jaggar, Jonathan H

    2014-11-01

    Plants high in eugenol, a phenylpropanoid compound, are used as folk medicines to alleviate diseases including hypertension. Eugenol has been demonstrated to relax conduit and ear arteries and reduce systemic blood pressure, but mechanisms involved are unclear. Here, we studied eugenol regulation of resistance-size cerebral arteries that control regional brain blood pressure and flow and investigated mechanisms involved. We demonstrate that eugenol dilates arteries constricted by either pressure or membrane depolarization (60 mM K) in a concentration-dependent manner. Experiments performed using patch-clamp electrophysiology demonstrated that eugenol inhibited voltage-dependent calcium (Ca) currents, when using Ba as a charge carrier, in isolated cerebral artery smooth muscle cells. Eugenol inhibition of voltage-dependent Ca currents involved pore block, a hyperpolarizing shift (∼-10 mV) in voltage-dependent inactivation, an increase in the proportion of steady-state inactivating current, and acceleration of inactivation rate. In summary, our data indicate that eugenol dilates cerebral arteries by means of multimodal inhibition of voltage-dependent Ca channels.

  12. Time- and concentration-dependent genomic responses of the rat airway to inhaled nickel subsulfide

    International Nuclear Information System (INIS)

    Objective: To provide insights into the mode of action for Ni3S2 lung carcinogenicity by examining gene expression changes in target cells after inhalation exposure. Methods: Gene expression changes were determined in micro-dissected lung broncho-alveolar cells from Fischer 344 rats following inhalation of Ni3S2 at 0.0, 0.04, 0.08, 0.15, and 0.60 mg/m3 (0.03, 0.06, 0.11, and 0.44 mg Ni/m3) for one and four weeks (6 h/day, 5 days/week). Results: Broncho-alveolar lavage fluid evaluation and lung histopathology provided evidence of inflammation only at the two highest concentrations, which were similar to those tested in the 2-year bioassay. The number of statistically significant up- and down-regulated genes decreased markedly from one to four weeks of exposure, suggesting adaptation. Cell signal pathway enrichment at both time-points primarily reflected responses to toxicity, including inflammatory and proliferative signaling. While proliferative signaling was up-regulated at both time points, some inflammatory signaling reversed from down-regulation at 1 week to up-regulation at 4 weeks. Conclusions: These results support a mode of action for Ni3S2 carcinogenicity driven by chronic toxicity, inflammation and proliferation, leading to mis-replication, rather than by direct genotoxicity. Benchmark dose (BMD) analysis identified the lowest pathway transcriptional BMD exposure concentration as 0.026 mg Ni/m3, for apoptosis/survival signaling. When conducted on the basis of lung Ni concentration the lowest pathway BMD was 0.64 μg Ni/g lung, for immune/inflammatory signaling. Implications: These highly conservative BMDs could be used to derive a point of departure in a nonlinear risk assessment for Ni3S2 toxicity and carcinogenicity. - Highlights: • The mode of action for lung carcinogenicity of inhaled Ni3S2 was investigated in rats. • Gene expression changes were determined in micro-dissected lung tissue at 1–4 weeks. • A non-genotoxic mode of action (toxicity

  13. Detection of Ca2+-dependent acid phosphatase activity identifies neuronal integrity in damaged rat central nervous system after application of bacterial melanin

    Directory of Open Access Journals (Sweden)

    Tigran R Petrosyan

    2016-01-01

    Full Text Available The study aims to confirm the neuroregenerative effects of bacterial melanin (BM on central nervous system injury using a special staining method based on the detection of Ca2+-dependent acid phosphatase activity. Twenty-four rats were randomly assigned to undergo either unilateral destruction of sensorimotor cortex (group I; n = 12 or unilateral rubrospinal tract transection at the cervical level (C3–4 (group II; n = 12. In each group, six rats were randomly selected after surgery to undergo intramuscular injection of BM solution (BM subgroup and the remaining six rats were intramuscularly injected with saline (saline subgroup. Neurological testing confirmed that BM accelerated the recovery of motor function in rats from both BM and saline subgroups. Two months after surgery, Ca2+-dependent acid phosphatase activity detection in combination with Chilingarian's calcium adenoside triphosphate method revealed that BM stimulated the sprouting of fibers and dilated the capillaries in the brain and spinal cord. These results suggest that BM can promote the recovery of motor function of rats with central nervous system injury; and detection of Ca2+-dependent acid phosphatase activity is a fast and easy method used to study the regeneration-promoting effects of BM on the injured central nervous system.

  14. Detection of Ca2+-dependent acid phosphatase activity identiifes neuronal integrity in damaged rat central nervous system after application of bacterial melanin

    Institute of Scientific and Technical Information of China (English)

    Tigran R Petrosyan; Anna S Ter-Markosyan; Anna S Hovsepyan

    2016-01-01

    The study aims to confirm the neuroregenerative effects of bacterial melanin (BM) on central nervous system injury using a special staining method based on the detection of Ca2+-dependent acid phosphatase activity. Twenty-four rats were randomly assigned to undergo either unilateral destruction of sensorimotor cortex (group I;n=12) or unilateral rubrospinal tract transection at the cervical level (C3–4) (group II;n=12). In each group, six rats were randomly selected after surgery to undergo intramuscular injection of BM solution (BM subgroup) and the remaining six rats were intramuscularly injected with saline (saline subgroup). Neurological testing confirmed that BM accelerated the recovery of motor function in rats from both BM and saline subgroups. Two months after surgery, Ca2+-dependent acid phosphatase activity detection in combination with Chilingarian’s calcium adenoside triphosphate method revealed that BM stimulated the sprouting of ifbers and dilated the capillaries in the brain and spinal cord. These results sug-gest that BM can promote the recovery of motor function of rats with central nervous system injury;and detection of Ca2+-dependent acid phosphatase activity is a fast and easy method used to study the regenera-tion-promoting effects of BM on the injured central nervous system.

  15. Detection of Ca(2+)-dependent acid phosphatase activity identifies neuronal integrity in damaged rat central nervous system after application of bacterial melanin.

    Science.gov (United States)

    Petrosyan, Tigran R; Ter-Markosyan, Anna S; Hovsepyan, Anna S

    2016-07-01

    The study aims to confirm the neuroregenerative effects of bacterial melanin (BM) on central nervous system injury using a special staining method based on the detection of Ca(2+)-dependent acid phosphatase activity. Twenty-four rats were randomly assigned to undergo either unilateral destruction of sensorimotor cortex (group I; n = 12) or unilateral rubrospinal tract transection at the cervical level (C3-4) (group II; n = 12). In each group, six rats were randomly selected after surgery to undergo intramuscular injection of BM solution (BM subgroup) and the remaining six rats were intramuscularly injected with saline (saline subgroup). Neurological testing confirmed that BM accelerated the recovery of motor function in rats from both BM and saline subgroups. Two months after surgery, Ca(2+)-dependent acid phosphatase activity detection in combination with Chilingarian's calcium adenoside triphosphate method revealed that BM stimulated the sprouting of fibers and dilated the capillaries in the brain and spinal cord. These results suggest that BM can promote the recovery of motor function of rats with central nervous system injury; and detection of Ca(2+)-dependent acid phosphatase activity is a fast and easy method used to study the regeneration-promoting effects of BM on the injured central nervous system. PMID:27630700

  16. Concentration dependence of the embryotoxic effects of benzene inhalation in CFY rats.

    Science.gov (United States)

    Tátrai, E; Ungváry, G; Hudák, A; Rodics, K; Lörincz, M; Barcza, G

    1980-01-01

    CFY rats were exposed to continuous benzene inhalation 24 h/day from day 7 to day 14 of gestation at 150, 450, 1500, or 3000 mg/m3 (50, 150, 500, or 1000 ppm) atmospheric concentrations. None of the benzene concentrations used proved to be teratogenic. There was no increase in the incidence of external, visceral, or skeletal malformations. Benzene inhalation at a 150 mg/m3 concentration brought about a slight toxic effect at a 450 mg/m3 concentration a more pronounced effect on both mothers and fetuses. The toxic effects were manifest as an increase in maternal mortality, circulatory damage, decreased gain in body weight, decrease in the weight of the placenta in the mothers and an increase in mortality (early and late), retardation of development (weight and skeleton) in the fetuses. No further change in the parameters was seen with further increases in benzene concentration. Avoidance of the risks of benzene exposure seems desirable before the commencement of planned pregnancy in the human.

  17. Effects of myosin light chain phosphorylation on length-dependent myosin kinetics in skinned rat myocardium.

    Science.gov (United States)

    Pulcastro, Hannah C; Awinda, Peter O; Breithaupt, Jason J; Tanner, Bertrand C W

    2016-07-01

    Myosin force production is Ca(2+)-regulated by thin-filament proteins and sarcomere length, which together determine the number of cross-bridge interactions throughout a heartbeat. Ventricular myosin regulatory light chain-2 (RLC) binds to the neck of myosin and modulates contraction via its phosphorylation state. Previous studies reported regional variations in RLC phosphorylation across the left ventricle wall, suggesting that RLC phosphorylation could alter myosin behavior throughout the heart. We found that RLC phosphorylation varied across the left ventricle wall and that RLC phosphorylation was greater in the right vs. left ventricle. We also assessed functional consequences of RLC phosphorylation on Ca(2+)-regulated contractility as sarcomere length varied in skinned rat papillary muscle strips. Increases in RLC phosphorylation and sarcomere length both led to increased Ca(2+)-sensitivity of the force-pCa relationship, and both slowed cross-bridge detachment rate. RLC-phosphorylation slowed cross-bridge rates of MgADP release (∼30%) and MgATP binding (∼50%) at 1.9 μm sarcomere length, whereas RLC phosphorylation only slowed cross-bridge MgATP binding rate (∼55%) at 2.2 μm sarcomere length. These findings suggest that RLC phosphorylation influences cross-bridge kinetics differently as sarcomere length varies and support the idea that RLC phosphorylation could vary throughout the heart to meet different contractile demands between the left and right ventricles. PMID:26763941

  18. Hippocampal state-dependent behavioral reflex to an identical sensory input in rats.

    Directory of Open Access Journals (Sweden)

    Keita Tokuda

    Full Text Available We examined the local field potential of the hippocampus to monitor brain states during a conditional discrimination task, in order to elucidate the relationship between ongoing brain states and a conditioned motor reflex. Five 10-week-old Wistar/ST male rats underwent a serial feature positive conditional discrimination task in eyeblink conditioning using a preceding light stimulus as a conditional cue for reinforced trials. In this task, a 2-s light stimulus signaled that the following 350-ms tone (conditioned stimulus was reinforced with a co-terminating 100-ms periorbital electrical shock. The interval between the end of conditional cue and the onset of the conditioned stimulus was 4±1 s. The conditioned stimulus was not reinforced when the light was not presented. Animals successfully utilized the light stimulus as a conditional cue to drive differential responses to the identical conditioned stimulus. We found that presentation of the conditional cue elicited hippocampal theta oscillations, which persisted during the interval of conditional cue and the conditioned stimulus. Moreover, expression of the conditioned response to the tone (conditioned stimulus was correlated with the appearance of theta oscillations immediately before the conditioned stimulus. These data support hippocampal involvement in the network underlying a conditional discrimination task in eyeblink conditioning. They also suggest that the preceding hippocampal activity can determine information processing of the tone stimulus in the cerebellum and its associated circuits.

  19. Extracellular Calcium-Dependent Modulation of Endothelium Relaxation in Rat Mesenteric Small Artery

    DEFF Research Database (Denmark)

    Hangaard, Lise; Jessen, Peter B; Kamaev, Dmitrii;

    2015-01-01

    The nature of NO- and COX-independent endothelial hyperpolarization (EDH) is not fully understood but activation of small- and intermittent-conductance Ca(2+)-activated K(+) channels (SKCa and IKCa) is important. Previous studies have suggested that the significance of IKCa depends on [Ca(2+)]out...

  20. Serum zinc concentrations in two cohorts of 153 healthy subjects and 100 cirrhotic patients from Mexico City.

    Science.gov (United States)

    Poo, J L; Rosas-Romero, R; Rodríguez, F; Silencio, J L; Muñoz, R; Bourges, H; Uribe, M

    1995-01-01

    The aim of this study was to assess serum zinc levels in a cohort of healthy subjects and cirrhotic patients from Mexico City. A total of 153 healthy subjects and 100 cirrhotic patients, males and females aged 18-65, were studied. Inclusion criteria for healthy subjects were (1) Mexican-born with first and second generation relatives born in Mexico, and (2) somatometric (body mass index under 30) and clinical evaluation establishing that they had no underlying disease. Entry criteria for cirrhotic patients were (1) clinical and histological proven cirrhosis, (2) compensated liver disease (absence of coma, bleeding hemorrhage or refractory ascitis), and (3) cirrhosis of any cause. Zinc serum levels were measured with atomic absorption spectrophotometry. In healthy subjects, mean serum levels were 77.4 +/- 4.2 micrograms/dl (range 42.9-105.2 micrograms/dl). In cirrhotic patients zinc serum levels (58.9 +/- 16.1 micrograms/dl, range 22-88 micrograms/dl) were significantly lower than in healthy subjects (p < 0.05). A stepwise decline in serum zinc with worsening Child class (A, 73.4 +/- 13; B, 64.4 +/- 12; C, 55.8 +/- 15.6; p < 0.05 by ANOVA test) was found. In conclusion, this study confirms that zinc serum levels are significantly lower in cirrhotic patients and shows that zinc serum levels in a cohort of 153 healthy subjects from Mexico City were unexpectedly lower compared to those found in other countries. This last finding might be explained by different dietetic patterns and deserves further investigation.

  1. State-dependent changes in auditory sensory gating in different cortical areas in rats.

    Directory of Open Access Journals (Sweden)

    Renli Qi

    Full Text Available Sensory gating is a process in which the brain's response to a repetitive stimulus is attenuated; it is thought to contribute to information processing by enabling organisms to filter extraneous sensory inputs from the environment. To date, sensory gating has typically been used to determine whether brain function is impaired, such as in individuals with schizophrenia or addiction. In healthy subjects, sensory gating is sensitive to a subject's behavioral state, such as acute stress and attention. The cortical response to sensory stimulation significantly decreases during sleep; however, information processing continues throughout sleep, and an auditory evoked potential (AEP can be elicited by sound. It is not known whether sensory gating changes during sleep. Sleep is a non-uniform process in the whole brain with regional differences in neural activities. Thus, another question arises concerning whether sensory gating changes are uniform in different brain areas from waking to sleep. To address these questions, we used the sound stimuli of a Conditioning-testing paradigm to examine sensory gating during waking, rapid eye movement (REM sleep and Non-REM (NREM sleep in different cortical areas in rats. We demonstrated the following: 1. Auditory sensory gating was affected by vigilant states in the frontal and parietal areas but not in the occipital areas. 2. Auditory sensory gating decreased in NREM sleep but not REM sleep from waking in the frontal and parietal areas. 3. The decreased sensory gating in the frontal and parietal areas during NREM sleep was the result of a significant increase in the test sound amplitude.

  2. Carnosine Content in Skeletal Muscle Is Dependent on Vitamin B6 Status in Rats

    OpenAIRE

    Suidasari, Sofya; Stautemas, Jan; Uragami, Shinji; Yanaka, Noriyuki; Derave, Wim; Kato, Norihisa

    2016-01-01

    Carnosine, a histidine-containing dipeptide, is well known to be associated with skeletal muscle performance. However, there is limited information on the effect of dietary micronutrients on muscle carnosine level. Pyridoxal 5′-phosphate (PLP), the active form of vitamin B6, is involved in amino acid metabolisms in the body as a cofactor. We hypothesized that enzymes involved in β-alanine biosynthesis, the rate-limiting precursor of carnosine, may also be PLP dependent. Thus, we examined the ...

  3. Nitrous Oxide Persistently Alleviates Pain Hypersensitivity in Neuropathic Rats: A Dose-Dependent Effect

    Directory of Open Access Journals (Sweden)

    Meric Ben Boujema

    2015-01-01

    Full Text Available BACKGROUND: Despite numerous pharmacological approaches, there are no common analgesic drugs that produce meaningful relief for the majority of patients with neuropathic pain. Although nitrous oxide (N2O is a weak analgesic that acts via opioid-dependent mechanisms, it is also an antagonist of the N-methyl-D-aspartate receptor (NMDAR. The NMDAR plays a critical role in the development of pain sensitization induced by nerve injury.

  4. Improvement of Endothelium-Dependent Relaxation in Aorta of Rat Models Type 1 and 2 Diabetes by Hespiridin

    Directory of Open Access Journals (Sweden)

    H Mirkhani,

    2008-07-01

    Full Text Available Background: Vascular disease is the principal cause of morbidity and mortality in patients with diabetes. A considerable body of evidence implicates oxidative stress as an important pathogenic factor of diabetic vasculopathies. In the present study, the effect of hesperidin, a flavanone glycoside with antioxidant activity, is studied in endothelium-dependent relaxation of the rat aorta in experimental diabetes mellitus type 1 (DM1 and type 2 (DM2. Patients and Methods: Single dose intraperitoneal injection of streptozocin (60mg/kg and subcutaneous daily injection of dexamethasone (10µg/kg for one month were used to induce DM1 and DM2, respectively. Hesperidin (500mg/kg was administered orally for two months in DM1 and one month in DM2. The effect of acetylcholine (Ach on phenyl ephrine (PE induced. PE contracted aorta was then studied and the EC50 and maximal relaxant effect of Ach were calculated and compared in the two groups.Results: In the experimental DM1, hesperidin restored endothelium-dependent relaxation near to those of normal animals. Its effect on experimental DM2 consisted of a significant reduction of EC50 value of Ach compared to those of diabetic animals. It also showed a great but non-significant effect (P=0.07 on Ach-induced maximum relaxation compared to DM2 untreated animals. Conclusion: These results show that hesperidin can improve vascular endothelial dysfunction in experimental diabetes mellitus.

  5. Matrine inhibited the growth of rat osteosarcoma UMR-108 cells by inducing apoptosis in a mitochondrial-caspase-dependent pathway.

    Science.gov (United States)

    Yan, Feng; Liu, Yang; Wang, Wenbo

    2013-08-01

    Matrine, one of the main active components of the extracts from the dry roots of Sophora flavescens, has a potent antitumor activity in vitro and in vivo. However, the molecular mechanism of cell apoptosis induced by matrine remains elusive. Here, we investigated the apoptosis in matrine-treated rat osteosarcoma UMR-108 cells. The results showed that matrine could inhibit cell proliferation and induce apoptosis in a dose- and time-dependent manner. Further investigation revealed a disruption of mitochondrial transmembrane potential and an upregulation of reactive oxygen species in matrine-treated cells. By western blot analysis, we found the upregulation of cleaved poly(ADP-ribose) polymerase, cleaved caspase-3, and cleaved caspase-9 and the downregulation of Bax/Bcl-2 with different concentrations of matrine. These protein interactions may play a pivotal role in the regulation of apoptosis. Taken together, these results overall indicate that matrine could be used as an effective antitumor agent in therapy of osteosarcoma targets the caspase-dependent signaling pathway.

  6. Nicotine induced pro-oxidant and antioxidant imbalance in rat lymphocytes: in vivo dose and time dependent approaches.

    Science.gov (United States)

    Das, Subhasis; Chakraborty, Subhankari Prasad; Roy, Soumyabrata; Roy, Somenath

    2012-11-01

    The immune cells use reactive oxygen species (ROS) for carrying out their normal functions while an excess amount of ROS can attack cellular components that lead to cell damage. The present study was undertaken to determine the dose as well as time dependent effects of nicotine administration on the superoxide anion generation, lipid peroxidation and antioxidant defense systems in lymphocytes. Male Wistar rats were treated with vehicle (normal saline) and nicotine [3-(1-methyl-2-pyrrolidinyl) pyridine, C(10)H(14)N(2)] (in physiological saline, pH was adjusted at 7.4 prior to injection) as indicated in a dose and duration fashion and the superoxide anion generation, lipid peroxidation, and antioxidant enzymes status were monitored. Superoxide anion generation, lipid peroxidation and oxidized glutathione levels were increased significantly (P activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-s-transferase were decreased significantly (P nicotine treatment. The highest changes in lymphocytes were observed at the dose of 1.0 mg/kg/day for 7 days. It may be concluded that nicotine is able to enhance the production of ROS that produced oxidative stress in lymphocytes in a dose and time dependent manner. PMID:22894698

  7. Co-administration of morphine and gabapentin leads to dose dependent synergistic effects in a rat model of postoperative pain.

    Science.gov (United States)

    Papathanasiou, Theodoros; Juul, Rasmus Vestergaard; Heegaard, Anne-Marie; Kreilgaard, Mads; Lund, Trine Meldgaard

    2016-01-20

    Despite much evidence that combination of morphine and gabapentin can be beneficial for managing postoperative pain, the nature of the pharmacological interaction of the two drugs remains unclear. The aim of this study was to assess the interaction of morphine and gabapentin in range of different dose combinations and investigate whether co-administration leads to synergistic effects in a preclinical model of postoperative pain. The pharmacodynamic effects of morphine (1, 3 and 7mg/kg), gabapentin (10, 30 and 100mg/kg) or their combination (9 combinations in total) were evaluated in the rat plantar incision model using an electronic von Frey device. The percentage of maximum possible effect (%MPE) and the area under the response curve (AUC) were used for evaluation of the antihyperalgesic effects of the drugs. Identification of synergistic interactions was based on Loewe additivity response surface analyses. The combination of morphine and gabapentin resulted in synergistic antihyperalgesic effects in a preclinical model of postoperative pain. The synergistic interactions were found to be dose dependent and the increase in observed response compared to the theoretical additive response ranged between 26 and 58% for the synergistic doses. The finding of dose-dependent synergistic effects highlights that choosing the right dose-dose combination is of importance in postoperative pain therapy. Our results indicate benefit of high doses of gabapentin as adjuvant to morphine. If these findings translate to humans, they might have important implications for the treatment of pain in postoperative patients.

  8. Duration-dependent hepatoprotective effects of propolis extract against carbon tetrachloride-induced acute liver damage in rats.

    Science.gov (United States)

    Bhadauria, Monika; Nirala, Satendra Kumar; Shukla, Sangeeta

    2007-01-01

    Propolis is a natural product produced by bees that was discovered through the study of traditional cures and knowledge of indigenous people throughout the world. It is rich in vitamins A, B, C, and E, and in amino acids, copper, iron, manganese, and zinc. The investigators studied the duration-dependent hepatoprotective effects of propolis extract (200 mg/kg, orally) against carbon tetrachloride (CCl 4; 1.5 mL/kg, intraperitoneally)-induced liver damage in rats. Administration of CCl 4 caused a sharp elevation in the activity of serum transaminases and serum alkaline phosphatase. A significant depletion in hepatically reduced glutathione was observed with significantly enhanced hepatic lipid peroxidation. After CCl 4 administration, glycogen contents and activities of alkaline phosphatase, adenosine triphosphatase, and succinic dehydrogenase were significantly decreased, whereas total protein contents and activity of acid phosphatase were increased in the liver and kidney. Propolis extract reversed alterations in all parameters when administered within 6, 12, and 24 h of toxicant exposure. Propolis therapy produced duration-dependent protection, with maximal protection achieved at 24 h after CCl 4 exposure. It is believed that propolis in its natural form has general pharmacologic value and marked hepatoprotective potential because of its composition of minerals, flavonoids, and phenolic compounds. PMID:18029340

  9. The ent-15α-Acetoxykaur-16-en-19-oic Acid Relaxes Rat Artery Mesenteric Superior via Endothelium-Dependent and Endothelium-Independent Mechanisms

    OpenAIRE

    Êurica Adélia Nogueira Ribeiro; Edla de Azevedo Herculano; Cintia Danieli Ferreira da Costa; Fabiola Fialho Furtado; Emídio Vasconcelos Leitão da-Cunha; José Maria Barbosa-Filho; Marcelo Sobral da Silva; Isac Almeida de Medeiros

    2012-01-01

    The objective of the study was to investigate the mechanism of the relaxant activity of the ent-15 α -acetoxykaur-16-en-19-oic acid (KA-acetoxy). In rat mesenteric artery rings, KA-acetoxy induced a concentration-dependent relaxation in vessels precontracted with phenylephrine. In the absence of endothelium, the vasorelaxation was significantly shifted to the right without reduction of the maximum effect. Endothelium-dependent relaxation was significantly attenuated by pretreatment with L-NAM...

  10. Cirrhotic cardiomyopathy

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens H

    2010-01-01

    Increased cardiac output was first described in patients with cirrhosis more than fifty years ago. Later, various observations have indicated the presence of a latent cardiac dysfunction, which includes a combination of reduced cardiac contractility with systolic and diastolic dysfunction and ele...

  11. Indomethacin injury to the rat small intestine is dependent upon biliary secretion and is associated with overgrowth of enterococci.

    Science.gov (United States)

    Mayo, Sara A; Song, Ye K; Cruz, Melissa R; Phan, Tri M; Singh, Kavindra V; Garsin, Danielle A; Murray, Barbara E; Dial, Elizabeth J; Lichtenberger, Lenard M

    2016-03-01

    NSAIDuse is limited due to the drugs' toxicity to the gastrointestinal mucosa, an action incompletely understood. Lower gut injury induced byNSAIDs is dependent on bile secretion and is reported to increase the growth of a number of bacterial species, including an enterococcal species,Enterococcus faecalis This study examined the relationships between indomethacin (INDO)-induced intestinal injury/bleeding, small bowel overgrowth (SBO) and dissemination of enterococci, and the contribution of bile secretion to these pathological responses. Rats received either a sham operation (SO) or bile duct ligation (BDL) prior to administration of two daily subcutaneous doses of saline orINDO, and 24 h later, biopsies of ileum and liver were collected for plating on selective bacterial media. Fecal hemoglobin (Hb) and blood hematocrit (Hct) were measured to assess intestinal bleeding. Of the four treatment groups, onlySO/INDOrats experienced a significant 10- to 30-fold increase in fecal Hb and reduction in Hct, indicating thatBDLattenuatedINDO-induced intestinal injury/bleeding. Ileal enterococcal colony-forming units were significantly increased (500- to 1000-fold) inSO/INDOrats. Of all groups, only theSO/INDOrats demonstrated gut injury, and this was associated with enterococcal overgrowth of the gut and dissemination to the liver. We also demonstrated thatINDO-induced intestinal injury andE. faecalisovergrowth was independent of the route of administration of the drug, as similar findings were observed in rats orally dosed with theNSAID Bile secretion plays an important role inINDO-induced gut injury and appears to support enterococcal overgrowth of the intestine.NSAID-induced enterococcalSBOmay be involved either as a compensatory response to gut injury or with the pathogenic process itself and the subsequent development of sepsis.

  12. Keratinocytes as depository of ammonium-inducible glutamine synthetase: age- and anatomy-dependent distribution in human and rat skin.

    Directory of Open Access Journals (Sweden)

    Lusine Danielyan

    Full Text Available In inner organs, glutamine contributes to proliferation, detoxification and establishment of a mechanical barrier, i.e., functions essential for skin, as well. However, the age-dependent and regional peculiarities of distribution of glutamine synthetase (GS, an enzyme responsible for generation of glutamine, and factors regulating its enzymatic activity in mammalian skin remain undisclosed. To explore this, GS localization was investigated using immunohistochemistry and double-labeling of young and adult human and rat skin sections as well as skin cells in culture. In human and rat skin GS was almost completely co-localized with astrocyte-specific proteins (e.g. GFAP. While GS staining was pronounced in all layers of the epidermis of young human skin, staining was reduced and more differentiated among different layers with age. In stratum basale and in stratum spinosum GS was co-localized with the adherens junction component beta-catenin. Inhibition of, glycogen synthase kinase 3beta in cultured keratinocytes and HaCaT cells, however, did not support a direct role of beta-catenin in regulation of GS. Enzymatic and reverse transcriptase polymerase chain reaction studies revealed an unusual mode of regulation of this enzyme in keratinocytes, i.e., GS activity, but not expression, was enhanced about 8-10 fold when the cells were exposed to ammonium ions. Prominent posttranscriptional up-regulation of GS activity in keratinocytes by ammonium ions in conjunction with widespread distribution of GS immunoreactivity throughout the epidermis allows considering the skin as a large reservoir of latent GS. Such a depository of glutamine-generating enzyme seems essential for continuous renewal of epidermal permeability barrier and during pathological processes accompanied by hyperammonemia.

  13. Protective effect of vitamin E on cypermethrin-induced follicular atresia in rat ovary: Evidence for energy dependent mechanism

    Science.gov (United States)

    Molavi, Morteza; Razi, Mazdak; Cheraghi, Hadi; Khorramjouy, Mona; Ostadi, Araz; Gholirad, Safa

    2016-01-01

    It has been shown that chronic exposure to cypermethrin (CPM), a pyrethroid pesticide, results in follicular atresia via pathologically affecting angiogenesis, disrupting endocrine potential and enhancing oxidative stress. This study was aimed to uncover the CPM-exposed energy dependent follicular cells apoptosis and to estimate protective effect of vitamin E (VitE) as a potent antioxidant. Thirty six Wistar rats were divided into six groups (n = 6 rats for each group) including; control-sham, CPM-received (CPM, 75 mg kg-1, intraperitoneally), and CPM and VitE-treated (VitE, 150 mg kg-1, orally) for 14 and 24 days. The protein biosynthesis of glucose transporter-1 (GLUT-1) and caspase-3 in follicles were estimated by using immuno-histochemical staining at preantral and antral stages. Moreover, the periodic acid Schiff (PAS) staining was performed in order to evaluate the intracytoplasmic carbohydrate ratio in follicular cells and oocyte. Percentages of follicles with GLUT-1, Caspase-3 and PAS-positive cells were compared between groups. Immunohistochemical analyses showed that, VitE significantly up-regulated the GLUT-1 expression and improved the intracytoplasmic carbohydrate supplementation especially at preantral follicles. The cross sections from the CPM-exposed ovaries represented remarkable elevation in percentage of atretic preantral and antral follicles with caspase-3 biosynthesis, which was remarkably (p < 0.05) diminished in VitE co-treated groups. In conclusion, our data showed that VitE by up-regulating of the GLUT-1 biosynthesis improved glucose uptake at follicular cells and oocyte levels that in turn inhibited pro-apoptotic protein caspase-3 biosynthesis. PMID:27482357

  14. Visualization of Time-Dependent Distribution of Rifampicin in Rat Brain Using MALDI MSI and Quantitative LCMS/MS.

    Science.gov (United States)

    Shobo, Adeola; Bratkowska, Dominika; Baijnath, Sooraj; Naiker, Suhashni; Bester, Linda A; Singh, Sanil D; Maguire, Glenn Eamond Mitchell; Kruger, Hendrik Gert; Govender, Thavendran

    2015-06-01

    Rifampicin (RIF) is a major component for short-course chemotherapy against tuberculosis, since it is active against rapidly metabolizing as well as dormant bacteria. According to the Lipinski rules, RIF should not enter the blood-brain barrier. Visualization of tissue drug distribution is of major importance in pharmacological studies; thus, far imaging of RIF in the brain has been limited to positron emission tomography. We propose using matrix-assisted laser desorption/ionization mass spectrometry imaging techniques as a suitable alternative for the visualization and localization of drug tissue distribution. Using the liquid chromatography mass spectrometric (LCMS) technique, we were able to quantify the concentrations of RIF in the uninfected rat brain; we paired this with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) to show the time-dependent manner in which RIF is able to enter the brain. Our results show that even at the minute concentrations measured with LCMS/MS we were able visualize the drug and show its exact distribution in the rat brain. Other available methods require nuclear labeling and the detection of gamma rays produced by labeled compounds to visualize the compound and its localization; MALDI MSI is a more recently developed technique, which can provide detailed information on drug distribution in tissues when compared to other imaging techniques. This study shows that without any requirement for complex preprocessing we are able to produce images with a relatively improved resolution and localization than those acquired using more complex imaging methods, showing MALDI MSI to be an invaluable tool in drug distribution studies.

  15. Carnosine content in skeletal muscle is dependent on vitamin B6 status in rats

    OpenAIRE

    Sofya eSuidasari; Jan eStautemas; Shinji eUragami; Noriyuki eYanaka; Wim eDerave; Norihisa eKato

    2016-01-01

    Carnosine, a histidine-containing dipeptide, is well known to be associated with skeletal muscle performance. However, there is limited information on the effect of dietary micronutrients on muscle carnosine level. Pyridoxal 5′-phosphate (PLP), the active form of vitamin B6, is involved in amino acid metabolisms in the body as a co-factor. We hypothesized that enzymes involved in β-alanine biosynthesis, the rate-limiting precursor of carnosine, may also be PLP-dependent. Thus, we examined the...

  16. Angiotensin Ⅱ type Ⅰ receptor agonistic autoantibody-induced apoptosis in neonatal rat cardiomyocytes is dependent on the generation of tumor necrosis factor-α

    Institute of Scientific and Technical Information of China (English)

    Weiran Chai; Wenhui Zhang; Zhu Jin; Yiping Feng; Yanping Kuang; Jianming Zhi

    2012-01-01

    Angiotensin Ⅱ type Ⅰ receptor agonistic autoantibodies (AT1-AA) are related to pre-eclampsia and hypertension and have a direct effect of stimulating the production of tumor necrosis factor-alpha (TNF-α) in the placenta.TNF-α is a known mediator of apoptosis.However,few studies have reported the role of TNF-α and its relationship within AT1-AA-induced apoptosis of cardiomyocytes.In this study,neonatal rat cardiomyocytes were treated with various concentrations of AT1-AA.The apoptosis of neonatal rat cardiomyocytes was determined using TUNEL assay and flow cytometry.The level of secreted TNF-α was measured by enzyme-linked immunosorbent assay,and caspase-3 activity was measured by a fluorogenic protease assay kit.AT1 receptor blockade and TNF inhibitor were added to determine whether they could inhibit the apoptotic effect of AT1-AA.Results showed that AT1-AA induced the apoptosis of neonatal rat cardiomyocytes in a dose-dependent and time-dependent manner.AT1-AA increased TNF secretion and caspase-3activities.AT1 receptor blockade completely abrogated AT1-AA-induced TNF-α secretion,caspase-3 activation,and cardiomyocyte apoptosis.TNF-α receptor inhibitor significantly attenuated AT1-AA-induced neonatal rat cardiomyocyte apoptosis.AT1-AA in the plasma of preeclamptic patients promoted neonatal rat cardiomyocyte apoptosis through a TNF-caspase signaling pathway.

  17. Significant long-term, but not short-term, hippocampal-dependent memory impairment in adult rats exposed to alcohol in early postnatal life.

    Science.gov (United States)

    Goodfellow, Molly J; Lindquist, Derick H

    2014-09-01

    In rodents, ethanol exposure in early postnatal life is known to induce structural and functional impairments throughout the brain, including the hippocampus. Herein, rat pups were administered one of three ethanol doses over postnatal days (PD) 4-9, a period of brain development comparable to the third trimester of human pregnancy. As adults, control and ethanol rats were trained and tested in a variant of hippocampal-dependent one-trial context fear conditioning. In Experiment 1, subjects were placed into a novel context and presented with an immediate footshock (i.e., within ∼8 sec). When re-exposed to the same context 24 hr later low levels of conditioned freezing were observed. Context pre-exposure 24 hr prior to the immediate shock reversed the deficit in sham-intubated and unintubated control rats, enhancing freezing behavior during the context retention test. Even with context pre-exposure, however, significant dose-dependent reductions in contextual freezing were seen in ethanol rats. In Experiment 2, the interval between context pre-exposure and the immediate shock was shortened to 2 hr, in addition to the standard 24 hr. Ethanol rats trained with the 2 hr, but not 24 hr, interval displayed retention test freezing levels roughly equal to controls. Results suggest the ethanol rats can encode a short-term context memory and associate it with the aversive footshock 2 hr later. In the 24 hr ethanol rats the short-term context memory is poorly transferred or consolidated into long-term memory, we propose, impeding the memory's subsequent retrieval and association with shock.

  18. Shifts in developmental timing, and not increased levels of experience-dependent neuronal activity, promote barrel expansion in the primary somatosensory cortex of rats enucleated at birth.

    Directory of Open Access Journals (Sweden)

    Ingrid Fetter-Pruneda

    Full Text Available Birth-enucleated rodents display enlarged representations of whiskers (i.e., barrels of the posteromedial subfield in the primary somatosensory cortex. Although the historical view maintains that barrel expansion is due to incremental increases in neuronal activity along the trigeminal pathway during postnatal development, recent evidence obtained in experimental models of intramodal plasticity challenges this view. Here, we re-evaluate the role of experience-dependent neuronal activity on barrel expansion in birth-enucleated rats by combining various anatomical methods and sensory deprivation paradigms. We show that barrels in birth-enucleated rats were already enlarged by the end of the first week of life and had levels of metabolic activity comparable to those in control rats at different ages. Dewhiskering after the postnatal period of barrel formation did not prevent barrel expansion in adult, birth-enucleated rats. Further, dark rearing and enucleation after barrel formation did not lead to expanded barrels in adult brains. Because incremental increases of somatosensory experience did not promote barrel expansion in birth-enucleated rats, we explored whether shifts of the developmental timing could better explain barrel expansion during the first week of life. Accordingly, birth-enucleated rats show earlier formation of barrels, accelerated growth of somatosensory thalamocortical afferents, and an earlier H4 deacetylation. Interestingly, when H4 deacetylation was prevented with a histone deacetylases inhibitor (valproic acid, barrel specification timing returned to normal and barrel expansion did not occur. Thus, we provide evidence supporting that shifts in developmental timing modulated through epigenetic mechanisms, and not increased levels of experience dependent neuronal activity, promote barrel expansion in the primary somatosensory cortex of rats enucleated at birth.

  19. The anorectic effect of GLP-1 in rats is nutrient dependent.

    Directory of Open Access Journals (Sweden)

    Darleen Sandoval

    Full Text Available GLP-1-induced insulin secretion from the β-cell is dependent upon glucose availability. The purpose of the current study was to determine whether CNS GLP-1 signaling is also glucose-dependent. We found that fasting blunted the ability of 3(rd cerebroventricularly (i3vt-administered GLP-1 to reduce food intake. However, fasted animals maintained the anorexic response to melanotan II, a melanocortin receptor agonist, indicating a specific effect of fasting on GLP-1 action. We also found that i3vt administration of leptin, which is also decreased with fasting, was not able to potentiate GLP-1 action in fasted animals. However, we did find that CNS glucose sensing is important in GLP-1 action. Specifically, we found that i3vt injection of 2DG, a drug that blocks cellular glucose utilization, and AICAR which activates AMPK, both blocked GLP-1-induced reductions in food intake. To examine the role of glucokinase, an important CNS glucose sensor, we studied glucokinase-heterozygous knockout mice, but found that they responded normally to peripherally administered GLP-1 and exendin-4. Interestingly, oral, but not i3vt or IP glucose potentiated GLP-1's anorectic action. Thus, CNS and peripheral fuel sensing are both important in GLP-1-induced reductions in food intake.

  20. Hepatocellular carcinoma associated with hereditary hemochromatosis occurring in non-cirrhotic liver.

    Science.gov (United States)

    von Delius, S; Lersch, C; Schulte-Frohlinde, E; Fend, F; Dobritz, M; Schmid, R M; Eckel, F

    2006-01-01

    The occurrence of primary hepatocellular carcinoma (HCC) in patients with hereditary hemochromatosis (HH) is well known. Thereby, the development of liver cirrhosis seems to be a prerequisite. Whether or not a hepatic iron overload in the context of hereditary hemochromatosis is an independent risk factor for HCC remains unclear. To date there are only a few reports about HCC arising in non-cirrhotic livers in the presence of HH. We report the case of a 64-year-old man who presented to our outpatient clinic with HCC. Liver cirrhosis could be excluded. Detailed exploration of the patient's history revealed that he had been treated by venesection for about 10 years up to 15 years ago. Subsequent investigations showed an elevated serum ferritin and transferrin saturation. The diagnosis of HH was confirmed by genetic testing, with homozygosity for the Cys282Tyr mutation. The patient received palliative chemotherapy and finally died 15 months after initial diagnosis of HCC. PMID:16397838

  1. Evaluation of leukocyte esterase and nitrite strip tests to detect spontaneous bacterial peritonitis in cirrhotic patients

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the diagnostic efficacy of leukocyte esterase and nitrite reagent strips for bedside diagnosis of spontaneous bacterial peritonitis (SBP).METHODS: A total of 63 consecutive patients with cirrhotic ascites (38 male, 25 female) tested between April 2005 and July 2006 were included in the study. Bedside reagent strip testing was performed on ascitic fluid and the results compared to manual cell counting and ascitic fluid culture. SBP was defined as having a olymorphonuclear ascites count of ≥ 250/mm3.RESULTS: Fifteen samples showed SBP. The sensitivity,specificity, positive and negative predictive values of the leukocyte esterase reagent strips were; 93%, 100%, 100%, and 98%, respectively. The sensitivity,specificity, positive and negative predictive value of the nitrite reagent strips were 13%, 93%, 40%, and 77%, respectively. The combination of leukocyte esterase and nitrite reagents strips did not yield statistically significant effects on diagnostic accuracy. CONCLUSION: Leukocyte esterase reagent strips may provide a rapid, bedside diagnostic test for SBP.

  2. Detection of antibodies against Fasciola hepatica in cirrhotic patients from Peru.

    Science.gov (United States)

    Marcos, L A; Bussalleu, A; Terashima, A; Espinoza, J R

    2009-03-01

    The prevalence of Fasciola hepatica infection, in endemic countries, in patients with established cirrhosis is unknown. We hypothesized that, in endemic countries, the presence of fascioliasis may be detected in a serum pool of cirrhotic patients. Forty-four previously stored serum samples of patients with established liver cirrhosis, in the Hospital Nacional Cayetano Heredia in Lima, Peru, were collected from 1998 to 2003 and assessed for hepatitis B, C and fascioliasis antibodies (Fas2 ELISA). Hepatitis B surface antigen (HBsAg) was positive in 8.8% (n = 34), hepatitis B core antibody (anti-HBc) in 32.5% (n = 34), hepatitis C antibodies (anti-HCV) in 9.1% (n = 33), and 9.1% (n = 44) were Fas2 ELISA positive. This disease is an example of an emerging tropical infection which can be present in chronic liver diseases, requiring greater clinician awareness especially in endemic rural areas. Further clinical studies are warranted. PMID:18817587

  3. Portal hemodynamics as predictors of high risk esophageal varices in cirrhotic patients

    Institute of Scientific and Technical Information of China (English)

    Mohammad K Tarzamni; Mohammad H Somi; Sara Farhang; Morteza Jalilvand

    2008-01-01

    AIM: To evaluate portal hypertension parameters in liver cirrhosis patients with and without esophageal varices (EV).METHODS: A cohort of patients with biopsy confirmed liver cirrhosis was investigated endoscopically and with color Doppler ultrasonography as a possible non-invasive predictive tool. The relationship between portal hemodynamics and the presence and size of EV was evaluated using uni- and multivariate approaches.RESULTS: Eighty five consecutive cirrhotic patients (43 men and 42 women) were enrolled. Mean age (± SD) was 47.5 (± 15.9). Portal vein diameter (13.88 ± 2.42 vs 12.00 ± 1.69, P 2.08 and spleen size > 15.05 cm. These factors may help identifying patients with a low probability of LEV who may not need upper gastrointestinal endoscopy.

  4. Age dependent differences in the regulation of hippocampal steroid hormones and receptor genes: relations to motivation and cognition in male rats.

    Science.gov (United States)

    Meyer, K; Korz, V

    2013-02-01

    Estrogen and estrogenic functions are age-dependently involved in the modulation of learning, memory and mood in female humans and animals. However, the investigation of estrogenic effects in males has been largely neglected. Therefore, we investigated the hippocampal gene expression of estrogen receptors α and β (ERα, β) in 8-week-old, 12-week-old and 24-week-old male rats. To control for possible interactions between the expression of the estrogen receptor genes and other learning-related steroid receptors, androgen receptors (AR), corticosterone-binding glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) were also measured. Furthermore, the concentrations of the ligands 17β-estradiol, testosterone and corticosterone were measured. The spatial training was conducted in a hole-board. The 8-week-old rats exhibited higher levels of general activity and exploration during the training and performed best with respect to spatial learning and memory, whereas no difference was found between the 12-week-old and 24-week-old rats. The trained 8-week-old rats exhibited increased gene expression of ERα compared with the untrained rats in this age group as well as the trained 12-week-old and 24-week-old rats. The concentrations of estradiol and testosterone, however, were generally higher in the 24-week-old rats than in the 8-week-old and 12-week-old rats. The ERα mRNA concentrations correlated positively with behavior that indicate general learning motivation. These results suggest a specific role of ERα in the age-related differences in motivation and subsequent success in the task. Thus, estrogen and estrogenic functions may play a more prominent role in young male behavior and development than has been previously assumed.

  5. The Mitochondria-Targeted Antioxidant SkQ1 Downregulates Aryl Hydrocarbon Receptor-Dependent Genes in the Retina of OXYS Rats with AMD-Like Retinopathy

    Directory of Open Access Journals (Sweden)

    M. L. Perepechaeva

    2014-01-01

    Full Text Available The mitochondria-targeted antioxidant SkQ1 is a novel drug thought to retard development of age-related diseases. It has been shown that SkQ1 reduces clinical signs of retinopathy in senescence-accelerated OXYS rats, which are a known animal model of human age-related macular degeneration (AMD. The aim of this work was to test whether SkQ1 affects transcriptional activity of AhR (aryl hydrocarbon receptor and Nrf2 (nuclear factor erythroid 2-related factor 2, which are considered as AMD-associated genes in the retina of OXYS and Wistar rats. Our results showed that only AhR and AhR-dependent genes were sensitive to SkQ1. Dietary supplementation with SkQ1 decreased the AhR mRNA level in both OXYS and Wistar rats. At baseline, the retinal Cyp1a1 mRNA level was lower in OXYS rats. SkQ1 supplementation decreased the Cyp1a1 mRNA level in Wistar rats, but this level remained unchanged in OXYS rats. Baseline Cyp1a2 and Cyp1b1 mRNA expression was stronger in OXYS than in Wistar rats. In the OXYS strain, Cyp1a2 and Cyp1b1 mRNA levels decreased as a result of SkQ1 supplementation. These data suggest that the Cyp1a2 and Cyp1b1 enzymes are involved in the pathogenesis of AMD-like retinopathy of OXYS rats and are possible therapeutic targets of SkQ1.

  6. The ethanol-induced stimulation of rat duodenal mucosal bicarbonate secretion in vivo is critically dependent on luminal Cl-.

    Directory of Open Access Journals (Sweden)

    Anna Sommansson

    Full Text Available Alcohol may induce metabolic and functional changes in gastrointestinal epithelial cells, contributing to impaired mucosal barrier function. Duodenal mucosal bicarbonate secretion (DBS is a primary epithelial defense against gastric acid and also has an important function in maintaining the homeostasis of the juxtamucosal microenvironment. The aim in this study was to investigate the effects of the luminal perfusion of moderate concentrations of ethanol in vivo on epithelial DBS, fluid secretion and paracellular permeability. Under thiobarbiturate anesthesia, a ∼30-mm segment of the proximal duodenum with an intact blood supply was perfused in situ in rats. The effects on DBS, duodenal transepithelial net fluid flux and the blood-to-lumen clearance of 51Cr-EDTA were investigated. Perfusing the duodenum with isotonic solutions of 10% or 15% ethanol-by-volume for 30 min increased DBS in a concentration-dependent manner, while the net fluid flux did not change. Pre-treatment with the CFTR inhibitor CFTRinh172 (i.p. or i.v. did not change the secretory response to ethanol, while removing Cl- from the luminal perfusate abolished the ethanol-induced increase in DBS. The administration of hexamethonium (i.v. but not capsazepine significantly reduced the basal net fluid flux and the ethanol-induced increase in DBS. Perfusing the duodenum with a combination of 1.0 mM HCl and 15% ethanol induced significantly greater increases in DBS than 15% ethanol or 1.0 mM HCl alone but did not influence fluid flux. Our data demonstrate that ethanol induces increases in DBS through a mechanism that is critically dependent on luminal Cl- and partly dependent on enteric neural pathways involving nicotinic receptors. Ethanol and HCl appears to stimulate DBS via the activation of different bicarbonate transporting mechanisms.

  7. Label-free bimodal waveguide immunosensor for rapid diagnosis of bacterial infections in cirrhotic patients.

    Science.gov (United States)

    Maldonado, Jesús; González-Guerrero, Ana Belén; Domínguez, Carlos; Lechuga, Laura M

    2016-11-15

    Spontaneous bacterial peritonitis is an acute bacterial infection of ascitic fluid; it has a high incidence in cirrhotic patients and it is associated with high mortality. In such a situation, early diagnosis and treatment is crucial for the survival of the patient. However, bacterial analysis in ascitic fluid is currently based on culture methods, which are time-consuming and laborious. We report here the application of a photonic interferometer biosensor based on a bimodal waveguide (BiMW) for the rapid and label-free detection of bacteria directly in ascitic fluid. The device consists of a straight waveguide in which two modes of the same polarization interfere while interacting with the external medium through their evanescent fields. A bimolecular event occurring on the sensor area of the device (e.g. capturing bacteria) will differently affect each light mode, inducing a variation in the phase of the light exiting at the output of the waveguide. In this work, we demonstrate the quantitative detection of Bacillus cereus in buffer medium and Escherichia coli in undiluted ascitic fluid from cirrhotic patients. In the case of Bacillus cereus detection, the device was able to specifically detect bacteria at relevant concentrations in 12.5min and in the case of Escherichia coli detection, the analysis time was 25min. Extrapolation of the data demonstrated that the detection limits of the biosensor could reach few bacteria per milliliter. Based on the results obtained, we consider that the BiMW biosensor is positioned as a promising new clinical tool for user-friendly, cost-effective and real-time microbiological analysis.

  8. Label-free bimodal waveguide immunosensor for rapid diagnosis of bacterial infections in cirrhotic patients.

    Science.gov (United States)

    Maldonado, Jesús; González-Guerrero, Ana Belén; Domínguez, Carlos; Lechuga, Laura M

    2016-11-15

    Spontaneous bacterial peritonitis is an acute bacterial infection of ascitic fluid; it has a high incidence in cirrhotic patients and it is associated with high mortality. In such a situation, early diagnosis and treatment is crucial for the survival of the patient. However, bacterial analysis in ascitic fluid is currently based on culture methods, which are time-consuming and laborious. We report here the application of a photonic interferometer biosensor based on a bimodal waveguide (BiMW) for the rapid and label-free detection of bacteria directly in ascitic fluid. The device consists of a straight waveguide in which two modes of the same polarization interfere while interacting with the external medium through their evanescent fields. A bimolecular event occurring on the sensor area of the device (e.g. capturing bacteria) will differently affect each light mode, inducing a variation in the phase of the light exiting at the output of the waveguide. In this work, we demonstrate the quantitative detection of Bacillus cereus in buffer medium and Escherichia coli in undiluted ascitic fluid from cirrhotic patients. In the case of Bacillus cereus detection, the device was able to specifically detect bacteria at relevant concentrations in 12.5min and in the case of Escherichia coli detection, the analysis time was 25min. Extrapolation of the data demonstrated that the detection limits of the biosensor could reach few bacteria per milliliter. Based on the results obtained, we consider that the BiMW biosensor is positioned as a promising new clinical tool for user-friendly, cost-effective and real-time microbiological analysis. PMID:27183281

  9. Expression of local renin and angiotensinogen mRNA in cirrhotic portal hypertensive patient

    Institute of Scientific and Technical Information of China (English)

    Li Zhang; Zhen Yang; Bao-Min Shi; Da-Peng Li; Chong-Yun Fang; Fa-Zu Qiu

    2003-01-01

    AIM: To investigate the expression of local renin and angiotensinogen mRNA in cirrhotic portal hypertensive patients.METHODS: The expression of local renin and angiotensinogen mRNA in the liver, splenic artery and vein of PH patients was detected by RT-PCR analysis.RESULTS: Expression of local renin mRNA in the liver of control group was (0.19±0.11), significantly lower than that in splenic artery(0.45±0.17)or splenic vein(0.39±0.12)respectively, (P<0.05). Expression of local angiotensinogen mRNA in the liver was (0.64±0.21), significantly higher than that in splenic artery(0.41±0.15) or in splenic vein (0.35±0.18)respectively, (P<0.05). Expression of local renin mRNA in the liver, splenic artery and vein of PH group was (0.78±0.28),(0.86±0.35) and (0.81±0.22) respectively, significantly higher than that in the control group, (P<0.05). Expression of local angiotensinogen mRNA in the liver, splenic artery and vein of PH group was (0.96±0.25), (0.83±0.18) and (0.79±0.23)respectively, significantly higher than that in the control group,(P<0.05). There was no significant difference between the liver, splenic artery and vein in the expression of local renin or local angiotensinogen mRNA in PH group, (P<0.05).CONCLUSION: In normal subjects the expression of local renin and angiotensinogen mRNA was organ specific, but with increase of the expression of LRAS, the organ-specificity became lost in cirrhotic patients. LRAS may contribute to increased resistance of portal vein with liver and formation of splanchnic vasculopathy.

  10. Portal hypertensive colopathy is associated with portal hypertension severity in cirrhotic patients

    Institute of Scientific and Technical Information of China (English)

    Antonio Diaz-Sanchez; Oscar Nu(n)ez-Martinez; Cecilia Gonzalez-Asanza; Ana Matilla; Beatriz Merino; Diego Rincon; Inmaculada Beceiro; Maria Vega Catalina; Magdalena Salcedo; Rafael Ba(n)ares; Gerardo Clemente

    2009-01-01

    AIM: To assess the prevalence of portal hypertension (PH) related colorectal lesions in liver transplant candidates, and to evaluate its association with the severity of PH.METHODS: Between October 2004 and December 2005, colonoscopy was performed in 92 cirrhotic liver transplant candidates. We described the lesions resulting from colorectal PH and their association with the grade of PH in 77 patients who underwent measurement of hepatic venous pressure gradient (HVPG). RESULTS: Mean age was 55 years and 80.7% of patients were men. The main etiology of cirrhosis was alcoholism (45.5%). Portal hypertensive colopathy (PHC) was found in 23.9%, colonic varices in 7.6% and polyps in 38% of patients (adenomatous type 65.2%). One asymptomatic patient had a well-differentiated adenocarcinoma. The manifestations of colorectal PH were not associated with the etiology of liver disease or with the Child-Pugh grade. Ninety percent of patients with colopathy presented with gastroesophageal varices (GEV), and 27.5% of patients with GEV presented with colopathy ( P = 0.12). A relationship between higher values of HVPG and presence of colopathy was observed (19.9 ± 6.2 mmHg vs 16.8 ± 5.4 mmHg, P = 0.045), but not with the grade of colopathy ( P = 0.13). Preneoplastic polyps and neoplasm ( P = 0.02) and spontaneous bacterial peritonitis ( P = 0.006) were more prevalent in patients with colopathy. We did not observe any association between previous β-blocker therapy and the presence of colorectal portal hypertensive vasculopathy. CONCLUSION: PHC is common in cirrhotic liver transplant candidates and is associated with higher portal pressure.

  11. Rats

    Directory of Open Access Journals (Sweden)

    Alexey Kondrashov

    2012-01-01

    Full Text Available We aimed to perform a chemical analysis of both Alibernet red wine and an alcohol-free Alibernet red wine extract (AWE and to investigate the effects of AWE on nitric oxide and reactive oxygen species production as well as blood pressure development in normotensive Wistar Kyoto (WKY and spontaneously hypertensive rats (SHRs. Total antioxidant capacity together with total phenolic and selected mineral content was measured in wine and AWE. Young 6-week-old male WKY and SHR were treated with AWE (24,2 mg/kg/day for 3 weeks. Total NOS and SOD activities, eNOS and SOD1 protein expressions, and superoxide production were determined in the tissues. Both antioxidant capacity and phenolic content were significantly higher in AWE compared to wine. The AWE increased NOS activity in the left ventricle, aorta, and kidney of SHR, while it did not change NOS activity in WKY rats. Similarly, increased SOD activity in the plasma and left ventricle was observed in SHR only. There were no changes in eNOS and SOD1 expressions. In conclusion, phenolics and minerals included in AWE may contribute directly to increased NOS and SOD activities of SHR. Nevertheless, 3 weeks of AWE treatment failed to affect blood pressure of SHR.

  12. Carbon Ion Irradiation of the Rat Spinal Cord: Dependence of the Relative Biological Effectiveness on Linear Energy Transfer

    Energy Technology Data Exchange (ETDEWEB)

    Saager, Maria, E-mail: m.saager@dkfz.de [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Department of Medical Physics in Radiation Oncology, German Cancer Research Center, Heidelberg (Germany); Glowa, Christin [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Department of Medical Physics in Radiation Oncology, German Cancer Research Center, Heidelberg (Germany); Peschke, Peter [Clinical Cooperation Unit Molecular Radiooncology, German Cancer Research Center, Heidelberg (Germany); Brons, Stephan [Heidelberg Ion Beam Therapy Center (HIT), Heidelberg (Germany); Scholz, Michael [Department of Biophysics, Helmholtz Center for Heavy Ion Research (GSI), Darmstadt (Germany); Huber, Peter E. [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Clinical Cooperation Unit Molecular Radiooncology, German Cancer Research Center, Heidelberg (Germany); Debus, Jürgen [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Karger, Christian P. [Department of Medical Physics in Radiation Oncology, German Cancer Research Center, Heidelberg (Germany)

    2014-09-01

    Purpose: To measure the relative biological effectiveness (RBE) of carbon ions in the rat spinal cord as a function of linear energy transfer (LET). Methods and Materials: As an extension of a previous study, the cervical spinal cord of rats was irradiated with single doses of carbon ions at 6 positions of a 6-cm spread-out Bragg peak (16-99 keV/μm). The TD{sub 50} values (dose at 50% complication probability) were determined according to dose-response curves for the development of paresis grade 2 within an observation time of 300 days. The RBEs were calculated using TD{sub 50} for photons of our previous study. Results: Minimum latency time was found to be dose-dependent, but not significantly LET-dependent. The TD{sub 50} values for the onset of paresis grade 2 within 300 days were 19.5 ± 0.4 Gy (16 keV/μm), 18.4 ± 0.4 Gy (21 keV/μm), 17.7 ± 0.3 Gy (36 keV/μm), 16.1 ± 1.2 Gy (45 keV/μm), 14.6 ± 0.5 Gy (66 keV/μm), and 14.8 ± 0.5 Gy (99 keV/μm). The corresponding RBEs increased from 1.26 ± 0.05 (16 keV/μm) up to 1.68 ± 0.08 at 66 keV/μm. Unexpectedly, the RBE at 99 keV/μm was comparable to that at 66 keV/μm. Conclusions: The data suggest a linear relation between RBE and LET at high doses for late effects in the spinal cord. Together with additional data from ongoing fractionated irradiation experiments, these data will provide an extended database to systematically benchmark RBE models for further improvements of carbon ion treatment planning.

  13. Sex-dependent behavioral changes in rat offspring after in utero administration of a single low dose PBDE 47

    Energy Technology Data Exchange (ETDEWEB)

    Kuriyama, S.N.; Talsness, C.E.; Chahoud, I. [Charite Univ. Medical School Berlin (Germany). Inst. of Clinical Pharmacology and Toxicology, Dept. Toxicology, Campus Benjamin Franklin

    2004-09-15

    Increasing levels of polybrominated diphenyl ethers (PBDEs) in environmental and human samples has resulted in intensive discussion regarding possible hazard identification and risk assessment in the last years. In rodents, exposure to PBDE mixtures or single congeners has resulted in a mixed induction of CYP450- dependent enzymes, showing increased activity of hepatic EROD and PROD. In addition, genotoxicity has been observed in recombination assays, and neurotoxicity has been reported in mice exposed during development. Acute and sub-chronic exposures of mice and rats to a PBDE mixture (DE-71) cause dose-dependent reductions in serum concentrations of thyroxin (T4), and stressinduced elevations in plasma corticosterone. Further, some hydroxylated metabolites of PBDE congeners exhibit a higher potency in vivo than T4 in competitive binding to human transthyretin (TTR), the transport protein mediating transfer of thyroid hormones across the placenta and into the brain. The available information in the literature clearly indicates that PBDEs are potent neurotoxicants, causing effects at doses lower than that able to disrupt thyroid hormone profiles and change CYP 450 activities. Neurobehavior effects, which includes defects in learning and memory, and changes in nicotinic receptors were found at doses starting at 0.45 ppm in mouse (9). The congeners, PBDE 47 and PBDE 99, have also been shown to cause permanent aberrations in spontaneous behavior in mice which was more pronounced with increasing age. PBDE 47 is the most predominant congener found in environmental and human samples, including human breast milk. Its presence in breast milk highlights the importance of evaluating possible effects following early developmental exposure and because this period represents a critical time which an organism is extremely susceptible to minor changes in hormonal milieu. Variances in terms of time point and concentration of exposure to steroids can lead to an organizational

  14. Enteral nutrients potentiate glucagon-like peptide-2 action and reduce dependence on parenteral nutrition in a rat model of human intestinal failure

    DEFF Research Database (Denmark)

    Brinkman, Adam S; Murali, Sangita G; Hitt, Stacy;

    2012-01-01

    Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent, proglucagon-derived gut hormone that shows promise for the treatment of short bowel syndrome (SBS). Our objective was to investigate how combination GLP-2 + enteral nutrients (EN) affects intestinal adaption in a rat model that mimics severe...... human SBS and requires parenteral nutrition (PN). Male Sprague-Dawley rats were assigned to one of five groups and maintained with PN for 18 days: total parenteral nutrition (TPN) alone, TPN + GLP-2 (100 μg·kg(-1)·day(-1)), PN + EN + GLP-2(7 days), PN + EN + GLP-2(18 days), and a nonsurgical oral...

  15. Basal efflux of bile acids contributes to drug-induced bile acid-dependent hepatocyte toxicity in rat sandwich-cultured hepatocytes.

    Science.gov (United States)

    Susukida, Takeshi; Sekine, Shuichi; Ogimura, Eiichiro; Aoki, Shigeki; Oizumi, Kumiko; Horie, Toshiharu; Ito, Kousei

    2015-10-01

    The bile salt export pump (BSEP or Bsep) functions as an apical transporter to eliminate bile acids (BAs) from hepatocytes into the bile. BSEP or Bsep inhibitors engender BA retention, suggested as an underlying mechanism of cholestatic drug-induced liver injury. We previously reported a method to evaluate BSEP-mediated BA-dependent hepatocyte toxicity by using sandwich-cultured hepatocytes (SCHs). However, basal efflux transporters, including multidrug resistance-associated proteins (MRP or Mrp) 3 and 4, also participate in BA efflux. This study examined the contribution of basal efflux transporters to BA-dependent hepatocyte toxicity in rat SCHs. The apical efflux of [(3)H]taurocholic acid (TC) was potently inhibited by 10 μM cyclosporine A (CsA), with later inhibition of basal [(3)H]TC efflux, while MK571 simultaneously inhibited both apical and basal [(3)H]TC efflux. CsA-induced BA-dependent hepatocyte toxicity was 30% at most at 10 μM CsA and ∼60% at 50 μM, while MK571 exacerbated hepatocyte toxicity at concentrations of ≥50 μM. Quinidine inhibited only basal [(3)H]TC efflux and showed BA-dependent hepatocyte toxicity in rat SCHs. Hence, inhibition of basal efflux transporters as well as Bsep may precipitate BA-dependent hepatocyte toxicity in rat SCHs. PMID:26055650

  16. The Effect of the First Spontaneous Bacterial Peritonitis Event on the Mortality of Cirrhotic Patients with Ascites: A Nationwide Population-Based Study in Taiwan

    OpenAIRE

    Hung, Tsung-Hsing; Tsai, Chen-Chi; Hsieh, Yu-Hsi; Tsai, Chih-Chun; Tseng, Chih-Wei; Tseng, Kuo-Chih

    2016-01-01

    Background/Aims Spontaneous bacterial peritonitis (SBP) contributes to poorer short-term mortality in cirrhotic patients with ascites. However, it is unknown how long the effect of the first SBP event persists in these patients. Methods The National Health Insurance Database, derived from the Taiwan National Health Insurance Program, was used to identify and enroll 7,892 cirrhotic patients with ascites who were hospitalized between January 1 and December 31, 2007. All patients were free from ...

  17. Postanoxic oxidative injury in rat hepatocytes: lactate-dependent protection against tert-butylhydroperoxide.

    Science.gov (United States)

    Kowalski, D P; Aw, T Y; Park, Y; Jones, D P

    1992-01-01

    Previous studies in this laboratory showed that hypoxia and anoxia enhance the susceptibility of hepatocytes to tert-butylhydroperoxide (TBH)-induced oxidative injury. To determine whether preceding exposure to anoxia affects postanoxic sensitivity to oxidative injury, viability was studied in hepatocytes incubated under anoxic conditions followed by reoxygenation without or with tert-butylhydroperoxide addition. Results showed that a preceding exposure to 60 min of anoxia substantially increased the vulnerability of cells to injury by the oxidant. Because substantial tissue lactate can accumulate during anoxia, the effect of increased lactate on postanoxic injury due to TBH was determined. Results showed that added lactate protected in a concentration-dependent manner. The TBH elimination rate was stimulated by lactate, and the pyruvate production rate approached the rate of TBH elimination. Thus, lactate protects against postanoxic oxidative injury by supplying reducing equivalents for peroxide reduction. This suggests that lactate accumulation during ischemia may be beneficial and that supplementation with lactate could be considered as a means to protect against postischemic injury. PMID:1563646

  18. Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Male Rats

    Data.gov (United States)

    U.S. Environmental Protection Agency — behavioral measures of learning and memory in adult offspring of rats treated with thyroid hormone synthesis inhibitor, propylthiouracil. Electrophysiological...

  19. The nondigestible disaccharide epilactose increases paracellular Ca absorption via rho-associated kinase- and myosin light chain kinase-dependent mechanisms in rat small intestines.

    Science.gov (United States)

    Suzuki, Takuya; Nishimukai, Megumi; Takechi, Maki; Taguchi, Hidenori; Hamada, Shigeki; Yokota, Atsushi; Ito, Susumu; Hara, Hiroshi; Matsui, Hirokazu

    2010-02-10

    We previously showed that epilactose, a nondigestible disaccharide, increased calcium (Ca) absorption in the small intestines of rats. Here, we explored the mechanism(s) underlying the epilactose-mediated promotion of Ca absorption in a ligated intestinal segment of anesthetized rats. The addition of epilactose to the luminal solution increased Ca absorption and chromium (Cr)-EDTA permeability, a paracellular indicator, with a strong correlation (R = 0.93) between these changes. Epilactose induced the phosphorylation of myosin regulatory light chains (MLCs), which is known to activate the paracellular route, without any change in the association of tight junction proteins with the actin cytoskeleton. The epilactose-mediated promotion of the Ca absorption was suppressed by specific inhibitors of myosin light chain kinase (MLCK) and Rho-associated kinase (ROCK). These results indicate that epilactose increases paracellular Ca absorption in the small intestine of rats through the induction of MLC phosphorylation via MLCK- and ROCK-dependent mechanisms.

  20. Hormone-dependent aggression in the female rat: testosterone plus estradiol implants prevent the decline in aggression following ovariectomy.

    Science.gov (United States)

    Albert, D J; Jonik, R H; Walsh, M L

    1991-04-01

    Female rats were individually housed with a sterile male for the duration of the experiment. Beginning 7 to 10 weeks after the start of cohabitation, each female was tested for aggression toward an unfamiliar female at weekly intervals for 3 weeks. Females that displayed consistent and substantial aggression were given one of the following treatments: ovariectomy followed by both testosterone and estradiol implants, ovariectomy followed by 2 empty implants, or sham ovariectomy followed by 2 empty implants. The implants were subcutaneously placed hormone-filled Silastic capsules. They were expected to produce a serum testosterone concentration of 0.5 ng/ml and an estradiol concentration of 15 pg/ml. Postoperatively, the aggression of each female continued to be assessed on a weekly basis for 3 weeks. Ovariectomized females with hormone implants displayed a level of aggression postoperatively similar to that of sham-ovariectomized females and significantly greater than that of ovariectomized females with empty implants. These results, together with others, suggest that estradiol and testosterone act together to form the hormonal foundation of hormone-dependent aggression by females cohabiting with a sterile male.

  1. Site-dependent effects of an acute intensive exercise on extracellular 5-HT and 5-HIAA levels in rat brain.

    Science.gov (United States)

    Gomez-Merino, D; Béquet, F; Berthelot, M; Chennaoui, M; Guezennec, C Y

    2001-03-30

    Previous neurochemical studies have reported different pattern of 5-HT release during exercise varying across either exercise conditions or forebrain sites. This in vivo microdialysis study is the first to examine the impact of an acute intensive treadmill running (2 h at 25 m.min(-1), which is close to exhaustion time), on extracellular 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in two different brain areas in rats, the ventral hippocampus and the frontal cortex. Hippocampal and cortical 5-HT levels increased significantly after 90 min of exercise and were maximal in the first 30 min of recovery. Thereafter, cortical 5-HT levels followed a rapid and significant decrease when hippocampal levels are still maximal. During exercise, changes in extracellular 5-HIAA levels paralleled 5-HT changes, but showed no difference between the two brain areas during recovery. Thus, an intensive exercise induces a delayed increase in brain 5-HT release but recovery seems to display site-dependent patterns. PMID:11248443

  2. The study of time dependent administration of methylphenidate on the microscopic indices of spermatogenesis and sperm analysis in adult rats

    Directory of Open Access Journals (Sweden)

    Shapour Hasanzadeh

    2013-04-01

    Full Text Available Objective: Methylphenidate, Ritalin, is one of the most common medications. The administration of Ritalin leads to increase of the activity of central nervous system. Ritalin may be used for maintaining alertness and improving of attention which, may lead to increase of the risk of substance abuse in some cases. There is a little data about the effects of long term treatment with Ritalin on body organs involved in fertility ability. Regarding to the effect of normal fertility on the physical and mental health of males, this study was designed to investigate the time dependent effects of MPH on the activity of male reproductive system. Methods: Ritalin was administrated to adult rats (10 mg/kg/day in three experimental groups for periods of two weeks, 11 weeks and 11 weeks with one week interval between each two weeks. The blood plasma levels of gonadotropins and testosterone was measured. Histomorphometrical study and sperm analysis was performed for evaluation of reproductive function. Results: The reduction in body weight and decline in the blood testosterone levels was seen in two groups which treated for 11 weeks. The reduction of microscopic indices of spermatogenesis and the alteration of morphometeric characteristics of seminiferous tubules was accompanied with epididymal sperm decrement in long term treated animals. Conclusion: The findings of this study indicate that, the long term use of methylphenidate can adversely damage the male fertility due to impairment of normal spermatogenesis. [J Exp Integr Med 2013; 3(2.000: 121-125

  3. Activity-dependent endogenous taurine release facilitates excitatory neurotransmission in the neocortical marginal zone of neonatal rats

    Directory of Open Access Journals (Sweden)

    Taizhe eQian

    2014-02-01

    Full Text Available In the developing cerebral cortex, the marginal zone (MZ, consisting of early-generated neurons such as Cajal-Retzius cells, plays an important role in cell migration and lamination. There is accumulating evidence of widespread excitatory neurotransmission mediated by γ-aminobutyric acid (GABA in the MZ. Cajal-Retzius cells express not only GABAA receptors but also α2/β subunits of glycine receptors, and exhibit glycine receptor-mediated depolarization due to high [Cl−]i. However, the physiological roles of glycine receptors and their endogenous agonists during neurotransmission in the MZ are yet to be elucidated. To address this question, we performed optical imaging from the MZ using the voltage-sensitive dye JPW1114 on tangential neocortical slices of neonatal rats. A single electrical stimulus evoked an action-potential-dependent optical signal that spread radially over the MZ. The amplitude of the signal was not affected by glutamate receptor blockers, but was suppressed by either GABAA or glycine receptor antagonists. Combined application of both antagonists nearly abolished the signal. Inhibition of Na+, K+-2Cl− cotransporter by 20 µM bumetanide reduced the signal, indicating that this transporter contributes to excitation. Analysis of the interstitial fluid obtained by microdialysis from tangential neocortical slices with high-performance liquid chromatography revealed that GABA and taurine, but not glycine or glutamate, were released in the MZ in response to the electrical stimulation. The ambient release of taurine was reduced by the addition of a voltage-sensitive Na+ channel blocker. Immunohistochemistry and immunoelectron microscopy indicated that taurine was stored both in Cajal-Retzius and non-Cajal-Retzius cells in the MZ, but was not localized in presynaptic structures. Our results suggest that activity-dependent non-synaptic release of endogenous taurine facilitates excitatory neurotransmission through activation of

  4. Breeder and batch-dependent variability in the acquisition and performance of a motor skill in adult Long-Evans rats.

    Science.gov (United States)

    O'Bryant, Amber J; Allred, Rachel P; Maldonado, Monica A; Cormack, Lawrence K; Jones, Theresa A

    2011-10-10

    Reaching tasks are popular tools for investigating the neural mechanisms of motor skill learning and recovery from brain damage in rodents, but there is considerable unexplained variability across studies using these tasks. We investigated whether breeder, batch effects, experimenter, time of year, weight and other factors contribute to differences in the acquisition and performance of a skilled reaching task, the single pellet retrieval task, in adult male Long-Evans hooded rats. First, we retrospectively analyzed task acquisition and performance in rats from different breeding colonies that were used in several studies spanning a 3 year period in our laboratory. Second, we compared reaching variables in age-matched rats from different breeders that were trained together as a batch by the same experimenters. All rats had received daily training on the reaching task until they reached a criterion of successful reaches per attempt. We found significant breeder-dependent differences in learning rate and final performance level. This was found even when age-matched rats from different breeders were trained together by the same experimenters. There was also significant batch-to-batch variability within rats from the same breeder trained by the same experimenter. Other factors, including weight, paw preference and the experimenter, were not as strong or consistent in their contributions to differences across studies. The breeder and batch effects found within the same rat strain may reflect genetic and environmental influences on the neural substrates of motor skill learning. This is an important consideration when comparing baseline performance across studies and for controlling variability within studies.

  5. Context-dependent differences in grooming behavior among the NIH heterogeneous stock and the Roman high- and low-avoidance rats.

    Science.gov (United States)

    Estanislau, C; Díaz-Morán, S; Cañete, T; Blázquez, G; Tobeña, A; Fernández-Teruel, A

    2013-12-01

    Grooming occurs during/after stress and seems to accompany dearousal. Here, grooming was investigated under testing situations involving different levels of aversiveness, taking advantage of differences among three rat strains in fearfulness/anxiety. Inbred Roman High Avoidance (RHA-I) rats are less anxious/fearful than inbred Roman Low Avoidance (RLA-I). The outbred genetically heterogeneous stock of rats (NIH-HS), which resembles the RLA-I in many behavioral traits, was also studied. Adult male rats (RLA-I: n=9, RHA-I: n=10, NIH-HS: n=12) were observed for 30min in: a novel open-field, a novel hole-board and in the home-cage. They were also observed during two-way active avoidance training. Differences in grooming depended on test situation: (a) No differences were found in the home-cage. (b) While tested in a novel environment, RHA-I showed less grooming activity than the other rats. (c) After avoidance responses appeared, differences among the strains were opposite to the observed in novelty tests. Furthermore, results suggest that (i) grooming is mostly suppressed when assured aversive experience is under way; (ii) rostral grooming prevails when experience with aversive stimuli is unpredictable (novelty) or potential (avoidance training); (iii) body grooming increases for a period in novel environments. In general, our results support that grooming takes place during dearousal.

  6. Age-related changes in microsome-dependent conversion of T -T ,thyroid function and cadmium toxicity in albino rat

    Directory of Open Access Journals (Sweden)

    Sohair A. Moustafa

    2002-09-01

    Full Text Available The impact of age on microsomal function, manifested by its ability to convert thyroid hormone thyroxine (T to triiodothyronine (T&, was investigated using four age '& (-months. The data show impaired microsomal function with advancing age represented by a significant decrease in serum levels of T& and T&/T ratio. There was a decline in the liver glutathione (GSH, total proteins and serum aspartate aminotransferase (AST, alanine aminotransferase (ALT and gamma-glutamyl transpeptidase (*GT. There was an-age associated increase in liver content of the lipid peroxidation products, thiobarituric acid (TBA-reactants and the serum total protein. + +,-.'( +-/' +-old+0-1-mg/kg CdCl 2their controls were injected with distilled water. A higher susceptibility of senile rats to cadmium toxicity was manifested as a significantly higher decrease in their serum T& level and T&/T ratio than adult compared to control. A reduction in the adaptive response of senile animals was manifested by a less increase in hepatic GSH in senile than adult as compared to control. The level of hepatic TBA-reactants was significantly higher in treated than in control group. The increase was more pronounced in the senile group. A marked hepatic cellular damage indicated by an increase in the serum levels of the AST and ALT was more pronounced in senile compared with adult rats. Treatment resulted in a decrease in the serum *GT and liver triglycerides (TG. The decrease in both parameters was more evident in senile as compared to adult group. Key words: Introduction As nations become progressively associated decline in the above more industrialized, the incidence of variables may be further complicated by overweight, non-insulin dependent disturbance in the normal metabolism diabetes mellitus (NIDDM, and related and action of thyroid hormones, metabolic disorders has been shown to particularly T& (Wallace & Hofmann, increase especially at old age. Along ((%263 4(((with those changes

  7. Prenatal stress programs neuroendocrine stress responses and affective behaviors in second generation rats in a sex-dependent manner.

    Science.gov (United States)

    Grundwald, Natalia J; Brunton, Paula J

    2015-12-01

    An adverse environment in early life is often associated with dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis and higher rates of mood disorders in adulthood. In rats, exposure to social stress during pregnancy results in hyperactive HPA axis responses to stress in the adult offspring and heightened anxiety behavior in the males, but not the females. Here we tested whether, without further intervention, the effects of prenatal stress (PNS) in the first filial generation (F1) are transmitted to the F2 generation via the maternal line. F1 control and PNS female rats were mated with control males and housed under non-stress conditions throughout pregnancy. HPA axis responses to acute stress, anxiety- and depressive-like behavior were assessed in the adult F2 offspring. ACTH and corticosterone responses to an acute stressor were markedly enhanced in F2 PNS females compared with controls. This was associated with greater corticotropin releasing hormone (Crh) mRNA expression in the paraventricular nucleus and reduced hippocampal glucocorticoid (Gr) and mineralocorticoid receptor (Mr) mRNA expression. Conversely, in the F2 PNS males, HPA axis responses to acute stress were attenuated and hippocampal Gr mRNA expression was greater compared with controls. F2 PNS males exhibited heightened anxiety-like behavior (light-dark box and elevated plus maze) compared with F2 control males. Anxiety-like behavior did not differ between F2 control and PNS females during metestrus/diestrus, however at proestrus/estrus, F2 control females displayed a reduction in anxiety-like behavior, but this effect was not observed in the F2 PNS females. Heightened anxiety in the F2 PNS males was associated with greater Crh mRNA expression in the central nucleus of the amygdala compared with controls. Moreover, Crh receptor-1 (Crhr1) mRNA expression was significantly increased, whereas Crhr2 mRNA was significantly decreased in discrete regions of the amygdala in F2 PNS males compared

  8. HOST RESISTANCE TO TRICHINELLA SPIRALIS INFECTION IN MICE AND RATS: SPECIES-DEPENDENT EFFECTS OF CYCLOPHOSPHAMIDE EXPOSURE

    Science.gov (United States)

    Host resistance to Trichinella spiralis infection was compared in rats (F344) and mice (C57BL/6J) following various cyclophosphamide (CY) treatment schedules. Dozes of CY given to mice were adjusted by body surface area to be comparable to rat doses. dult parasite elimination was...

  9. Propofol versus midazolam for upper gastrointestinal endoscopy in cirrhotic patients: a meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Hsiao-Chien Tsai

    Full Text Available Sedation during gastrointestinal endoscopy is often achieved using propofol or midazolam in general population. However, impaired protein synthesis, altered drug metabolism, and compromised hepatic blood flow in patients with liver cirrhosis might affect the pharmacokinetics of sedatives, placing cirrhotic patients undergoing endoscopy at a greater risk of adverse events. The objective of this study was to assess comparative efficacies and safety of propofol and midazolam in cirrhotic patients undergoing endoscopy.Randomized, controlled trials comparing propofol with midazolam in cirrhotic patients undergoing gastrointestinal endoscopy were selected. We performed the meta-analysis, using a random-effect model, the Review Manager, Version 5.2, statistical software package (Cochrane Collaboration, Oxford, UK according to the PRISMA guidelines.Five studies between 2003 and 2012, including 433 patients, were included. Propofol provided a shorter time to sedation (weight mean difference: -2.76 min, 95% confidence interval: -3.00 to -2.51 and a shorter recovery time (weight mean difference -6.17 min, 95% confidence interval: -6.81 to -5.54 than midazolam did. No intergroup difference in the incidence of hypotension, bradycardia, or hypoxemia was observed. Midazolam was associated with the deterioration of psychometric scores for a longer period than propofol.This meta-analysis suggests that Propofol sedation for endoscopy provides more rapid sedation and recovery than midazolam does. The risk of sedation-related side effects for propofol does not differ significantly from that of midazolam. The efficacy of propofol in cirrhotic patients undergoing endoscopy is superior to those of midazolam.

  10. In the non-cirrhotic stage of nonalcoholic steatohepatitis, angioarchitecture of portal veins and lobular architecture are maintained

    OpenAIRE

    Hano, Hiroshi; Takasaki, Satoshi; Kobayashi, Hirohiko; Koyama, Tomoki; Lu, Tomoe; Nagatsuma, Keisuke

    2013-01-01

    The morphogenesis of lobular restructuring to liver cirrhosis in nonalcoholic steatohepatitis (NASH) is yet to be clearly understood. Therefore, we observed tissue samples from three biopsies and one autopsy with NASH in the non-cirrhotic stage three-dimensionally to elucidate the evolution of fibrosis and the changes of angioarchitecture. Histologic reconstructions revealed that pericellular fibrosis developed around the central vein in the early stage and gradually progressed to arch-shaped...

  11. Relationship of 24-hour ambulatory blood pressure and heart rate with markers of hepatic function in cirrhotic patients

    OpenAIRE

    Stergiou George S; Dourakis Spyros P; Alexopoulou Alexandra; Tzamouranis Dimitris G

    2010-01-01

    Abstract Background There is evidence that in cirrhotic patients, certain hemodynamic parameters, such as blood pressure and heart rate, are related to the severity of liver disease. This study investigated whether non-invasive 24-hour ambulatory blood pressure and heart rate are more closely associated with markers of liver disease severity than conventional office measurements. Methods Ambulatory patients with cirrhosis underwent office blood pressure and heart rate measurements, 24-hour am...

  12. Classification tool for the systematic histological assessment of hepatocellular carcinoma, macroregenerative nodules, and dysplastic nodules in cirrhotic liver

    Institute of Scientific and Technical Information of China (English)

    A Quaglia; MA Jutand; A Dhillon; A Godfrey; R Togni; P Bioulac-Sage; C Balabaud; M Winnock; AP Dhillon

    2005-01-01

    AIM: To design a classification tool for the histological assessment of hepatocellular carcinoma (HCC), dysplastic nodules (DN), and macroregenerative nodules (MRN) in cirrhotic liver.METHODS: Two hundred and twelve hepatocellular nodules (106 HCC;74 MRN;32 DN) were assessed systematically, quantitatively, and semiquantitatively as appropriate for 10 histological features that have been described as helpful in distinguishing small HCC, DN, and MRN in cirrhotic livers. The data were analyzed by multiple correspondence analysis (MCA).RESULTS: MCA distributed HCC, DN, and MRN as defined by traditional histological evaluation as well as the individual histological variables, in a "malignancy scale".Based on the MCA data representation, we created a classification tool, which categorizes an individual nodular lesion as MRN, DN, or HCC based on the balance of all histological features (i.e., vascular invasion, capsular invasion, tumor necrosis, tumor heterogeneity, reticulin loss,capillarization of sinusoids, trabecular thickness, nuclear atypia, and mitotic activity). The classification tool dassified most (83%) of a validation set of 47 nodules in the same way as the routine histological assessment. No discrepandes were present for DN and MRN between the routine histological assignment and the classification tool. Of 25 HCC assigned by routine assessment in the validation set, 8were assigned to the DN category by the classification tool.CONCLUSION: We have designed a classification tool for the histological assessment of HCC and its putative precursors in cirrhotic liver. Application of this tool systematically records histological features of diagnostic importance in the evaluation of small HCC.

  13. Management of digestive bleeding related to portal hypertension in cirrhotic patients: A French multicenter cross-sectional practice survey

    Institute of Scientific and Technical Information of China (English)

    Pierre Ingrand; Jean-Claude Barbare; Isabelle Ingrand; Michel Beauchant; Jér(o)me Gournay; Pierre Bernard; Frédéric Oberti; Brigitte Bernard-Chabert; Arnault Pauwels; Philippe Renard; Eric Bartoli; Jean-Fran(c)ois Cadranel

    2006-01-01

    AIM: To investigate the conformity of management practices of gastrointestinal hemorrhage in cirrhotic patients with relevant guidelines.METHODS: A questionnaire on the management of digestive bleeding was completed for all consecutive cirrhotic patients admitted to 31 French hospitals.RESULTS: One hundred and twenty-six bleeding events were recorded. It was the first bleeding episode in 79 patients (63%), of whom 40 (51%) had a prior diagnosis of cirrhosis and 25 (32%) had previously undergone an endoscopy. The bleeding episode was a recurrence in 46 patients (37%). The median time between onset and admission was 4 h, but exceeded 12 h in 42% of cases. There was an agreement between centers for early vasoactive drug administration (87% of cases),association with ligation (42%) more often than sclerosis (21%) at initial endoscopy, and antibiotic prophylaxis (64%). By contrast, prescription of beta-blockade alone or in combination (0 to 100%, P = 0.003) for secondary prophylaxis and lactulose (26% to 86%, P = 0.04),differed among centers.CONCLUSION: In French hospitals, management of bleeding related to portal hypertension in cirrhotic patients is generally in keeping with the consensus.Broad variability still remains concerning beta-blockade use for secondary prophylaxis. Screening for esophageal varices, the use of antibiotic prophylaxis and patients information need to be improved.

  14. Lymphatic marker podoplanin/D2-40 in human advanced cirrhotic liver- Re-evaluations of microlymphatic abnormalities

    Directory of Open Access Journals (Sweden)

    Yoshimura Kazunori

    2010-11-01

    Full Text Available Abstract Background From the morphological appearance, it was impossible to distinguish terminal portal venules from small lymphatic vessels in the portal tract even using histochemical microscopic techniques. Recently, D2-40 was found to be expressed at a high level in lymphatic endothelial cells (LECs. This study was undertaken to elucidate hepatic lymphatic vessels during progression of cirrhosis by examining the expression of D2-40 in LECs. Methods Surgical wedge biopsy specimens were obtained from non-cirrhotic portions of human livers (normal control and from cirrhotic livers (LC (Child A-LC and Child C-LC. Immunohistochemical (IHC, Western blot, and immunoelectron microscopic studies were conducted using D2-40 as markers for lymphatic vessels, as well as CD34 for capillary blood vessels. Results Imunostaining of D2-40 produced a strong reaction in lymphatic vessels only, especially in Child C-LC. It was possible to distinguish the portal venules from the small lymphatic vessels using D-40. Immunoelectron microscopy revealed strong D2-40 expression along the luminal and abluminal portions of the cell membrane of LECs in Child C-LC tissue. Conclusion It is possible to distinguish portal venules from small lymphatic vessels using D2-40 as marker. D2-40- labeling in lymphatic capillary endothelial cells is related to the degree of fibrosis in cirrhotic liver.

  15. Proteomic analysis of age dependent nitration of rat cardiac proteins by solution isoelectric focusing coupled to nano-HPLC tandem mass spectrometry

    OpenAIRE

    Hong, Sung Jung; Gokulrangan, Giridharan; Schöneich, Christian

    2007-01-01

    Protein nitration occurs as a result of oxidative stress induced by reactive oxygen (ROS) and reactive nitrogen species (RNS). Therefore, protein nitration serves as a hallmark for protein oxidation in vivo. We have previously reported on age dependent protein nitration in cardiac tissue of Fisher 344 BN-F1 rats analyzed by two-dimensional gel electrophoresis; however, only one specific nitration site was identified (Kanski et al., 2005a). In the present report, we used solution phase isoelec...

  16. HISS-dependent insulin resistance (HDIR) in aged rats is associated with adiposity, progresses to syndrome X, and is attenuated by a unique antioxidant cocktail

    OpenAIRE

    Lautt, W. Wayne; Ming, Zhi; Macedo, M Paula; Legare, Dallas J.

    2008-01-01

    The hypotheses were: HISS-dependent insulin resistance (HDIR) accounts for insulin resistance that occurs with aging; HDIR is the initiating metabolic defect that leads progressively to type 2 diabetes and the metabolic syndrome; a synergistic antioxidant cocktail in chow confers protection against HDIR, subsequent symptoms of diabetes, and the metabolic syndrome. Male Sprague Dawley rats were tested at 9, 26, and 52 weeks to determine their dynamic response to insulin, the HISS (hepatic insu...

  17. Inhibitory Effect of the Melanocortin Receptor Agonist Melanotan-II (MTII) on Feeding Depends on Dietary Fat Content and not Obesity in Rats on Free-Choice Diets

    OpenAIRE

    José K van den Heuvel; Eggels, Leslie; van Rozen, Andrea J.; Fliers, Eric; Kalsbeek, Andries; Adan, Roger A. H.; la Fleur, Susanne E

    2015-01-01

    Introduction: Conflicting data exist on sensitivity changes of the melanocortin system during diet-induced obesity. We hypothesized that melanocortin sensitivity depends on diet composition, in particular on the fat content rather than the level of obesity. The aim of this study was to determine the influence of diet composition on feeding responses to a melanocortin receptor agonist, using free-choice diets that differ in food components. Methods: Male Wistar rats were subjected to a chow...

  18. Increased secretory demand rather than a defect in the proinsulin conversion mechanism causes hyperproinsulinemia in a glucose-infusion rat model of non-insulin-dependent diabetes mellitus.

    OpenAIRE

    Alarcón, C; Leahy, J L; Schuppin, G T; Rhodes, C. J.

    1995-01-01

    Hyperproinsulinemia in non-insulin-dependent diabetes mellitus (NIDDM) is due to an increased release of proinsulin from pancreatic beta cells. This could reside in increased secretory demand placed on the beta cell by hyperglycemia or in the proinsulin conversion mechanism. In this study, biosynthesis of the proinsulin conversion enzymes (PC2, PC3, and carboxypeptidase-H [CP-H]) and proinsulin, were examined in islets isolated from 48-h infused rats with 50% (wt/vol) glucose (hyperglycemic, ...

  19. Selective inhibition of a slow-inactivating voltage-dependent K+ channel in rat PC12 cells by hypoxia.

    Science.gov (United States)

    Conforti, L; Millhorn, D E

    1997-07-15

    1. Electrophysiological (single-channel patch clamp) and molecular biological experiments (reverse transcriptase-polymerase chain reaction) were performed to attempt to identify the O2-sensitive K+ channel in rat phaeochromocytoma (PC12) cells. 2. Four types of K+ channels were recorded in PC12 cells: a small-conductance K+ channel (14 pS), a calcium-activated K+ channel (KCa; 102 pS) and two K+ channels with similar conductance (20 pS). These last two channels differed in their time-dependent inactivation: one was a slow-inactivating channel, while the other belonged to the family of fast transient K+ channels. 3. The slow-inactivating 20 pS K+ channel was inhibited by hypoxia. Exposure to hypoxia produced a 50% reduction in channel activity (number of active channels in the patch x open probability). Hypoxia had no effect on the 20 pS transient K+ channels, whereas reduced O2 stimulated the KCa channels. 4. The genes encoding the alpha-subunits of slow-inactivating K+ channels for two members of the Shaker subfamily of K+ channels (Kv1.2 and Kv1.3) together with the Kv2.1, Kv3.1 and Kv3.2 channel genes were identified in PC12 cells. 5. The expression of the Shaker Kv1.2, but none of the other K+ channel genes, increased in cells exposed to prolonged hypoxia (18 h). The same cells were more responsive to a subsequent exposure to hypoxia (35% inhibition of K+ current measured in whole-cell voltage clamp) compared with the cells maintained in normoxia (19% inhibition). 6. These results indicate that the O2-sensitive K+ channel in PC12 cells is a 20 pS slow-inactivating K+ channel that is upregulated by hypoxia. This channel appears to belong to the Shaker subfamily of voltage-gated K+ channels. PMID:9263911

  20. Locality-dependent descending reflex motor activity in the anal canal-cholinergic and nitrergic contributions in the rat model

    Institute of Scientific and Technical Information of China (English)

    Radomir RADOMIROV; Christina IVANCHEVA; Dimitar ITZEV; Polina PETKOVA-KIROVA

    2009-01-01

    Aim: Since the distal part of the intestine is targeted by a wide range of pathogens, the motility of the recto-anal region has been the object of many experimental and clinical observations. In this study, we investigated descending motor responses in the anal canal as a measure of the activation of autonomic reflex pathways underlying evacuatory recto-anal activity. Methods: The partitioned organ bath method was used to register motor responses of the anal canal as induced by balloon distension of the rectum in isolated rat recto-anal preparations. Results: Distension-induced descending responses of the anal canal comprised contractions (with distension at a distance of 15 mm), initial contractions and secondary relaxations (at 10 mm) and short contractions followed by deep relaxations (at 3-5 mm). Decreas-ing the distance between the distension stimulus and the anal canal resulted in a decreased contraction response and increased relaxation. Tetrodotoxin (0.1 μmol/L) inhibited these responses. Atropine (0.3 μmol/L) decreased contraction and did not change the relaxation response. N~G-nitro-L-arginine (0.5 mmol/L) enhanced contraction in both the absence and presence of atropine. L-arginine (0.5 mmol/L) inhibited contraction and extended relaxation in atropine-pretreated preparations. The actions of N~G-nitro-L-arginine and L-arginine were more pronounced in the aboral direction. ChAT-positive nerve fibers were observed in myenteric ganglia of the rectum and the anal canal. The density of NADPH-diaphorase-positive neurons was higher in the anal canal region. Conclusion: Our results suggest that locality-dependent activation of the descending reflex neuromuscular communications underlie evacuatory activity in the recto-anal region. This activation response involves long excitatory cholinergic and non-cholinergic pathways along the rectum and short inhibitory nitrergic pathways located predominantly in the anal canal region.

  1. Steroid modulation of the chloride ionophore in rat brain: structure-activity requirements, regional dependence and mechanism of action

    Energy Technology Data Exchange (ETDEWEB)

    Gee, K.W.; Bolger, M.B.; Brinton, R.E.; Coirini, H.; McEwen, B.S.

    1988-08-01

    Further in vitro studies of steroids active at the gamma-aminobutyric acidA (GABAA) receptor regulated Cl- channel labeled by (35S)-t-butylbicyclophosphorothionate ((35S)TBPS) reveal additional structural requirements necessary for activity. Evaluation of selected steroids for activity against TBPS-induced convulsions show similar requirements for activity. Interestingly, steroids (e.g., 5 alpha-pregnan-3 alpha, 20 alpha-diol) were identified that have high potency but limited efficacy as modulators of (35S)TBPS binding. These characteristics are reminiscent of the clinically useful benzodiazepines (BZs) such as clonazepam. However, interactions between the prototypical anesthetic-barbiturate, sodium pentobarbital, and steroids active at the Cl- channel suggest that they do not share a common site of action as allosteric modulators of (35S)TBPS and BZ receptor binding. The most potent steroid evaluated, 5 alpha-pregnan-3 alpha-ol-20-one, modulates (35S)TBPS binding at low concentrations (IC50 approximately 17 nM) in a regionally dependent manner. All (35S)TBPS binding sites appear to be functionally coupled to a steroid modulatory site. Because several of the active steroids are metabolites of progesterone, their ability to inhibit the binding of (3H)promegestrone to the cytosolic progestin receptor in rat uterus was evaluated. Those steroids showing potent activity at the GABAA receptor-Cl- ionophore were inactive at the intracellular progestin receptor. Such specificity coupled with their high potency provide additional support for the hypothesis that some of these steroids may be involved in the homeostatic regulation of brain excitability via the GABAA-BZ receptor complex.

  2. Steroid modulation of the chloride ionophore in rat brain: structure-activity requirements, regional dependence and mechanism of action

    International Nuclear Information System (INIS)

    Further in vitro studies of steroids active at the gamma-aminobutyric acidA (GABAA) receptor regulated Cl- channel labeled by [35S]-t-butylbicyclophosphorothionate ([35S]TBPS) reveal additional structural requirements necessary for activity. Evaluation of selected steroids for activity against TBPS-induced convulsions show similar requirements for activity. Interestingly, steroids (e.g., 5 alpha-pregnan-3 alpha, 20 alpha-diol) were identified that have high potency but limited efficacy as modulators of [35S]TBPS binding. These characteristics are reminiscent of the clinically useful benzodiazepines (BZs) such as clonazepam. However, interactions between the prototypical anesthetic-barbiturate, sodium pentobarbital, and steroids active at the Cl- channel suggest that they do not share a common site of action as allosteric modulators of [35S]TBPS and BZ receptor binding. The most potent steroid evaluated, 5 alpha-pregnan-3 alpha-ol-20-one, modulates [35S]TBPS binding at low concentrations (IC50 approximately 17 nM) in a regionally dependent manner. All [35S]TBPS binding sites appear to be functionally coupled to a steroid modulatory site. Because several of the active steroids are metabolites of progesterone, their ability to inhibit the binding of [3H]promegestrone to the cytosolic progestin receptor in rat uterus was evaluated. Those steroids showing potent activity at the GABAA receptor-Cl- ionophore were inactive at the intracellular progestin receptor. Such specificity coupled with their high potency provide additional support for the hypothesis that some of these steroids may be involved in the homeostatic regulation of brain excitability via the GABAA-BZ receptor complex

  3. Sex-dependent effects of an early life treatment in rats that increases maternal care: vulnerability or resilience?

    Directory of Open Access Journals (Sweden)

    Silvia eFuentes

    2014-02-01

    Full Text Available Early life stress (ELS in rodents has profound long-term effects that are partially mediated by changes in maternal care. ELS not only induces detrimental effects in adulthood, increasing psychopathology, but also promotes resilience to further stressors. In Long-Evans rats, we evaluated a combination of two procedures as a model of ELS: restriction of bedding during the first postnatal days and exposure to a substitute mother. The maternal care of biological and substitute mothers was measured. The male and female offspring were evaluated during adulthood in several contexts. Anxiety was measured by the elevated plus-maze (EPM, acoustic startle response (ASR and forced swim test (FST. In other group of animals, novelty-seeking was measured (activity in an inescapable novel environment, preference for novel environments and exploration of novel objects. Plasmatic ACTH and corticosterone in basal conditions and in response to stress were also measured. Cognitive impulsivity was assessed by a delay-discounting paradigm, and impulsive action, attention and compulsive-like behaviour by a five choice serial reaction time task (5CSRTT. ELS decreased pup body weight and increased the care of the biological mother; however, the substitute mother did not exhibit overt maltreatment. A mixture of detrimental and beneficial effects was shown. In the 5CSRTT, attention was impaired in both genders, and in females, ELS increased compulsive-like behaviour. Novel object exploration was only increased by ELS in males, but the preference for novel spaces decreased in both genders. Baseline anxiety (EPM and ASR and recognition memory were not affected. Unexpectedly, ELS decreased the ACTH response to novelty and swim stress and increased active coping in the FST in both genders. Cognitive impulsivity was decreased only in females, but impulsive action was not affected. The enhancement in maternal care may buffer the effects of ELS in a context-dependent manner.

  4. Cytoplasmic androgen binding protein of rat liver: molecular characterization after photoaffinity labeling and functional correlation with the age-dependent synthesis of alpha 2u-globulin

    International Nuclear Information System (INIS)

    The liver of the mature male rat contains a moderate affinity (Kd = 10(-8)M), low-capacity, cytoplasmic androgen binding protein (CAB) whose appearance during puberty and disappearance during senescence correlate with the androgen-dependent synthesis of alpha 2u-globulin. Molecular properties of CAB were examined by photoaffinity labeling with tritiated methyltrienolone (R-1881), a synthetic androgen, and by its localization within the hepatocytes which are competent to produce alpha 2u-globulin. Photoaffinity labeling of the liver cytosol derived from postpubertal male rats, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography, showed a predominant androgen binding band corresponding to Mr 31,000. This 31-kilodalton (kDa) binding component was conspicuously absent in the liver of androgen-insensitive prepubertal and senescent male rats and in adult male rats treated with estradiol-17 beta. In addition, unlike the cytoplasmic extract, the nuclear lysate of the male rat hepatocytes did not contain the 31-kDa androgen binder. Disappearance of the 31-kDa androgen binding band from the cytosolic fraction of androgen-insensitive animals was associated with a concomitant appearance of a minor androgen binding component of apparent Mr 29,000. The livers of postpubertal male rats normally contain two subpopulations of hepatocytes, only one of which is highly active (competent) in alpha 2u-globulin synthesis. Separation of these two subpopulations through a fluorescence-activated cell sorter followed by whole cell labeling showed more than a 2-fold higher uptake of R-1881 by the competent cells

  5. Chronic ethanol intake-induced changes in open-field behavior and calcium/calmodulin-dependent protein kinase Ⅳ expression in nucleus accumbens of rats: naloxone reversal

    Institute of Scientific and Technical Information of China (English)

    Jing LI; Wei-liang BIAN; Gui-qin XIE; Sheng-zhong CUI; Mei-ling WU; Yue-hua LI; Ling-li QUE; Xiao-ru YUAN

    2008-01-01

    Aim: To investigate the effects of chronic ethanol intake on the locomotor activity and the levels of calcium/calmodulin-dependent protein kinase Ⅳ (CaM kinase Ⅳ) in the nucleus accumbens (NAc) of rats. Simultaneously, the effects of non-selective opioid antagonist (naloxone) on the CaM kinase Ⅳ expression in the NAc and ethanol consumption of rats were also observed. Methods: Ethanol was administered in drinking water at the concentrations of 6% (v/v), for 28 d. The locomotor activity of rats was investigated in the open-field apparatus. CaM kinase Ⅳ levels in the NAc were analyzed using Western blotting. Results: Rats consuming ethanol solution exhibited a significant decrease of ambulation activity, accompanied by a reduced frequency of explorative rearing in an open-field task on d 7 and d 14 of chronic ethanol ingestion, whereas presumed adaptation to the neurological effects of ethanol was observed on d 28. Chronic ethanol intake elicited a significant decrease of the CaM kinase Ⅳ expression in the nuclei, but not in the cytoplasm of the NAc on d 28. Naloxone treatment significantly attenu-ated ethanol intake of rats and antagonized the decrease of CaM kinase Ⅳ in the nuclei of NAc neurons. The cytosolic CaM kinase Ⅳ protein levels of the NAc also increased in rats exposed to ethanol plus naloxone. Conclusion: Chronic ethanol intake-induced changes in explorative behavior is mediated at least partly by changes in CaM kinase Ⅳ signaling in the nuclei of the NAc, and naloxone attenuates ethanol consumption through antagonizing the downregulation of CaM kinase Ⅳ in the NAc.

  6. Hippocampal-dependent spatial memory in the water maze is preserved in an experimental model of temporal lobe epilepsy in rats.

    Directory of Open Access Journals (Sweden)

    Marion Inostroza

    Full Text Available Cognitive impairment is a major concern in temporal lobe epilepsy (TLE. While different experimental models have been used to characterize TLE-related cognitive deficits, little is known on whether a particular deficit is more associated with the underlying brain injuries than with the epileptic condition per se. Here, we look at the relationship between the pattern of brain damage and spatial memory deficits in two chronic models of TLE (lithium-pilocarpine, LIP and kainic acid, KA from two different rat strains (Wistar and Sprague-Dawley using the Morris water maze and the elevated plus maze in combination with MRI imaging and post-morten neuronal immunostaining. We found fundamental differences between LIP- and KA-treated epileptic rats regarding spatial memory deficits and anxiety. LIP-treated animals from both strains showed significant impairment in the acquisition and retention of spatial memory, and were unable to learn a cued version of the task. In contrast, KA-treated rats were differently affected. Sprague-Dawley KA-treated rats learned less efficiently than Wistar KA-treated animals, which performed similar to control rats in the acquisition and in a probe trial testing for spatial memory. Different anxiety levels and the extension of brain lesions affecting the hippocampus and the amydgala concur with spatial memory deficits observed in epileptic rats. Hence, our results suggest that hippocampal-dependent spatial memory is not necessarily affected in TLE and that comorbidity between spatial deficits and anxiety is more related with the underlying brain lesions than with the epileptic condition per se.

  7. Identification, characterization, and hormonal regulation of 3', 5'-cyclic adenosine monophosphate-dependent protein kinases in rat Sertoli cells.

    Science.gov (United States)

    Landmark, B F; Fauske, B; Eskild, W; Skålhegg, B; Lohmann, S M; Hansson, V; Jahnsen, T; Beebe, S J

    1991-11-01

    Recent studies have disclosed multiple isoforms of regulatory (R) and catalytic (C) subunits of cAMP-dependent protein kinase (PKA) at the protein and messenger RNA (mRNA) levels. The purpose of the present study was to identify, characterize, and quantify individual R subunits in rat Sertoli cells both at the mRNA and protein levels. Unstimulated Sertoli cells contain high levels of R (approximately 9.2 +/- 0.8 pmol/mg protein) and C (approximately 7.3 +/- 0.7 pmol/mg protein). Stimulation with (Bt)2cAMP (0.1 mM) for 24 and 48 h revealed a time-dependent increase in [3H]cAMP-binding activity. During the same time period the catalytic activity remained relatively constant, resulting in an increase in the R/C ratio from approximately 1.3 to 3.0. Using diethylaminoethyl cellulose chromatography, 8-N3-[32P]cAMP photoaffinity labeling, autophosphorylation by gamma-[32P]ATP, and specific antibodies, we show that unstimulated Sertoli cells contain approximately 75% RI alpha, 25% RII alpha, and very low levels of RII beta. Stimulation of Sertoli cells with (Bt)2cAMP (0.1 mM, 48 h) was associated with a 2.1-fold increase in RI alpha (6.6-14 pmol/mg) and a 10- to 20-fold increase in RII beta (less than 0.1-1.1 pmol/mg), with little or no change in RII alpha (1.9-2.3 pmol/mg). Treatment with cAMP was associated with a slight increase in RI/RII ratio (3.3-4.1). mRNA levels for RII beta increased 30- to 50-fold after (Bt)2cAMP stimulation, whereas only minor changes in mRNA levels for RI alpha, RII alpha, and C alpha were observed (1.5- to 2.0-fold). mRNA levels for RI beta, C beta, and C gamma were not detected in either unstimulated or in cAMP-stimulated Sertoli cells. It is concluded that chronic treatment with cAMP changes the relative proportion of R subunits of PKA in a manner reflecting the changing levels in respective mRNAs. Furthermore, such treatment is associated with the appearance of a new PKA R subunit (RII beta), which is absent in untreated Sertoli cells. PMID

  8. Clinical usefulness of Tc-99M pertechnetate per-rectal portal scintigraphy in evaluation the severity of portal hypertension in cirrhotic patients

    International Nuclear Information System (INIS)

    Objectives: Variceal hemorrhage is a potentially life-threatening complication in cirrhotic patients. Identification of patients at high risk for bleeding is particularly important. The aim of this study was to determine the clinical usefulness of per-rectal portal scintigraphy in evaluation the severity of portal hypertension in cirrhotic patients in terms of correlation between cirrhosis and classic indicators of hepatic functional reserve and identifying the difference of the portal shunt index (PSI) of the bleeding esophageal varices group and non-bleeding esophageal varices group. Material and methods: Portal circulations in 15 healthy volunteer's and in 67 patients with cirrhosis were evaluated by Tc-99m pertechnetate per-rectal p. ortal scintigraphy. Tc-99m pertechnetate (550 MBq) was instilled into the upper rectum, and dynamic images were taken. Radioactivity curves of the liver and the heart were generated sequentially. Through the analysis of these curves, the PSI was determined by calculating the ratio of counts of the liver to counts of the heart integrated for 24 seconds immediately after the appearance of the liver time-activity curve. Results: The results, expressed as PSI were: 13.63 +/- 6.28 % in healthy subjects and 66.32+/-22.80 % in cirrhotic patients. Of these, the PSIs were 56036 +/- 27.14 % in 31 cirrhotic patients without esophageal varices, and 74.89 +/- 13.62 % in 36 cirrhotic patients with esophageal varices. The PSI was significantly lower in cirrhotic patients without bleeding esophageal vances (BEV) than those with BEV (p=0.001). The PSI calculated with this method was correlated with the serum albumin, the serum bilirubin and the Child-Pugh's score. Conclusion: The Tc-99m pertechnetate per-rectal portal scintigraphy has clinical usefulness as a relatively non-invasive method of choice for quantitative evaluating the severity of portal hypertension in cirrhotic patients. (authors)

  9. Heat shock protein 70-dependent protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells

    OpenAIRE

    Qin, Ying; NAITO, Yuji; Handa, Osamu; Hayashi, Natsuko; Kuki, Aiko; Mizushima, Katsura; Omatsu, Tatsushi; Tanimura, Yuko; Morita, Mayuko; Adachi, Satoko; Fukui, Akifumi; Hirata, Ikuhiro; Kishimoto, Etsuko; Nishikawa, Taichiro; Uchiyama, Kazuhiko

    2011-01-01

    Protection of the small intestine from mucosal injury induced by nonsteroidal anti-inflammatory drugs including acetylsalicylic acid is a critical issue in the field of gastroenterology. Polaprezinc an anti-ulcer drug, consisting of zinc and L-carnosine, provides gastric mucosal protection against various irritants. In this study, we investigated the protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of the RIE1 rat intestinal epithelial cell line. Confluent rat intest...

  10. Peripheral blood cell variations in cirrhotic portal hypertension patients with hypersplenism

    Institute of Scientific and Technical Information of China (English)

    Yun-Fu Lu; Xin-Qiu Li; Xiao-Yu Han; Xiao-Guang Gong; Shun-Wu Chang

    2013-01-01

    Objective:To explore peripheral blood cell variations in hepatic cirrhosis portal hypertension patients with hypersplenism. Methods: Clinical data of 322 hypersplenism patients with decreased peripheral blood cells, admitted with cirrhotic portal hypertension, was retrospectively studied over the last 17 years. Results:In 64% (206/322) of patients, more than 2 kinds of blood cell were decreased, including 89 cases of pancytopenia (43.2%), 52 cases of WBC+PLT decrease (25.2%), 29 cases of RBC + PLT decrease (14.1%), and 36 cases of WBC + RBC decrease (17.5%);in 36% (116/322) of patients, single type blood cell decrease occurred, including 31 cases of PLT decrease (26.7%), 29 cases of WBC decrease (25%) and 56 cases of RBC decrease (48.3%). Of 227 routine bone marrow examinations, bone marrow hyperplasia was observed in 118 cases (52.0%), the remainder showed no hyperplasia. For the distinct scope and extent of peripheralblood cell decreases, preoperative blood component transfusions were carried out, then treated by surgery, after whole group splenectomy, the peripheral blood cell count was significantly higher (P<0.05). Conclusions: Of portal hypertensive patients with splenomegaly and hypersplenism, 64%have simultaneous decrease in various blood cells, 36%have decrease in single type blood cells, 52%of patients have bone marrow hyperplasia. A splenectomy can significantly increase the reduction of peripheral blood cells.

  11. From listing to transplant: nephrologic monitoring in cirrhotic patients awaiting liver transplantation.

    Science.gov (United States)

    Umbro, I; Tinti, F; Fiacco, F; Zavatto, A; Di Natale, V; Ginanni Corradini, S; Rossi, M; Poli, L; Berloco, P B; Mitterhofer, A P

    2013-09-01

    Nephrologic monitoring of end-stage liver disease (ESLD) patients is part of evaluation for orthotopic liver transplantation (OLT). The numerous causes of renal dysfunction in ESLD patients sometimes relate to the extent of liver damage or sometimes more closely to organic nephropathy. The aim of this study was to evaluate renal function through a specific nephrologic form applied in our outpatient clinic to optimize nephrologic monitoring in ESLD patients awaiting OLT. We enrolled 69 cirrhotic patients (56 men, 13 women) awaiting OLT from April 2008 to January 2012. All patients were evaluated at listing and every 3 months until OLT. The most interesting result was the stable values of serum creatinine from listing to transplantation. We think that dedicated liver transplant nephrologic evaluation is important in the follow-up of ESLD patients awaiting OLT, because the presence of renal dysfunction may represent an important criterion for specific therapeutic interventions to minimize pre-OLT renal injuries that limit the effect of impaired renal function on patient outcomes.

  12. Systemic chemotherapy for hepatocellular carcinoma in non-cirrhotic liver: A retrospective study

    Institute of Scientific and Technical Information of China (English)

    Julien Edeline; Jean-Luc Raoul; Elodie Vauleon; Anne Guillygomac'h; Karim Boudjema; Eveline Boucher

    2009-01-01

    AIM: To investigate the efficacy and toxicity of systemic chemotherapy in a retrospective study of patients with hepatocellular carcinoma (HCC) occurring in normal or fibrotic liver without cirrhosis. METHODS: Twenty-four patients with metastatic or locally advanced HCC in a normal or a fibrotic liver were given systemic chemotherapy (epirubicin, cisplatin and 5-fluorouracil or epirubicin, cisplatin and capecitabine regimens). Tumor response, time to progression, survival, and toxicity were evaluated. RESULTS: There were 7 women and 17 men, mean 6 had a fibrotic liver (F1/F2 on biopsy). Mean tumor size was 14 cm, 5 patients had portal vein thrombosis and 7 had metastasis. Patients received a median of 4 chemotherapy sessions. Overall tolerance was good. There were 5 partial responses (objective response rate = 22%), and tumor control rate was 52%. Second line surgical resection was possible in two patients. Median survival was 11 mo, and 1- and 2-year overall survival rates were 50% ± 10% and 32% ± 11%, respectively. ``CONCLUSION: In patients with HCC in a non-cirrhotic liver, chemotherapy was well tolerated and associated with an objective response rate of 22%, including two patients who underwent secondary surgical resection.

  13. Hepatocellular carcinoma in cirrhotic patients with portal hypertension: Is liver resection always contraindicated?

    Institute of Scientific and Technical Information of China (English)

    Andrea Ruzzenente; Alessandro Valdegamberi; Tommaso Campagnaro; Simone Conci; Silvia Pachera; Calogero Iacono,; Alfredo Guglielmi

    2011-01-01

    AIM: To analyze the outcome of hepatocellular carcinoma (HCC) resection in cirrhosis patients, related to presence of portal hypertension (PH) and extent of hepatectomy. METHODS: A retrospective analysis of 135 patients with HCC on a background of cirrhosis was submitted to curative liver resection. RESULTS: PH was present in 44 (32.5%) patients. Overall mortality and morbidity were 2.2% and 33.7%, respectively. Median survival time in patients with or without PH was 31.6 and 65.1 mo, respectively (P = 0.047); in the subgroup with Child-Pugh class A cirrhosis, median survival was 65.1 mo and 60.5 mo, respectively (P = 0.257). Survival for patients submitted to limited liver resection was not significantly different in presence or absence of PH. Conversely, median survival for patients after resection of 2 or more segments with or without PH was 64.4 mo and 163.9 mo, respectively (P = 0.035). CONCLUSION: PH is not an absolute contraindication to liver resection in Child-Pugh class A cirrhotic patients, but resection of 2 or more segments should not be recommended in patients with PH.

  14. Developmental changes of cytochrome P450 dependent monooxygenase functions after transplantation of fetal liver tissue suspension into spleens of adult syngenic rats.

    Science.gov (United States)

    Lupp, A; Trautmann, A K; Krausse, T; Klinger, W

    1998-06-01

    Fetal liver tissue suspensions were transplanted into the spleens of adult male syngenic Fisher 344 inbred rats. Animals were sacrificed at 3 days, 1, 2, 4 weeks, and 2, 4 and 6 months after transplantation and cytochrome P450 (P450) dependent monooxygenase functions in spleen and liver 9000 g supernatants were assessed by measuring three model reactions for different P450 subtypes: ethoxyresorufin O-deethylation (EROD; mainly 1A), ethoxycoumarin O-deethylation (ECOD; predominantly 1A, 2A, 2B) and ethylmorphine N-demethylation (END; mainly 3A). Values of transplant recipients were compared to those of sham operated and age matched control rats. Spleen weights were significantly higher in transplanted rats, compared to controls or sham operated animals, but there was no influence of the transplants within the spleens on liver weights. With fetal livers at the 21st day of gestation, the day of transplantation, a weak EROD and ECOD, but no END activity was seen. Spleens of controls or sham operated animals displayed nearly no P450 mediated monooxygenase functions. In the explant containing spleens a significant and increasing EROD activity was found from 4 weeks after surgery on and an ECOD activity already 2 weeks after transplantation. END was only slightly enhanced at 6 months after surgery. The livers of all three groups of rats displayed normal EROD, ECOD and END activities. Transplantation of fetal liver tissue suspensions into the spleens did not influence the P450 dependent monooxygenase functions within the livers of the animals. From these results it can be concluded that intrasplenically transplanted liver cells originating from syngenic fetal liver tissue suspensions proliferate and differentiate within the host organs. They display P450 dependent monooxygenase functions with some developmental changes during the observed time period of 6 months.

  15. Acetylcholine- and sodium hydrosulfide-induced endothelium-dependent relaxation and hyperpolarization in cerebral vessels of global cerebral ischemia-reperfusion rat.

    Science.gov (United States)

    Han, Jun; Chen, Zhi-Wu; He, Guo-Wei

    2013-01-01

    We investigated the effects of endothelium-derived hyperpolarizing factor (EDHF) and the role of hydrogen sulphide (H2S) in the cerebral vasorelaxation induced by acetylcholine (ACh) in global cerebral ischemia-reperfusion (CIR) rats. CIR was induced by occlusion of bilateral carotid and vertebral arteries. Isolated arterial segments from the cerebral basilar (CBA) and middle artery (MCA) of CIR rats were studied in a pressurized chamber. Transmembrane potential was recorded using glass microelectrodes to evaluate hyperpolarization. In the CIR CBAs and MCAs preconstricted by 30 mM KCl, ACh induced concentration-dependent vasorelaxation and hyperpolarization that were partially attenuated by NG-nitro-l-arginine methyl ester (l-NAME, 30 μM) and l-NAME plus indomethacin (10 μM). The residual responses were abolished by the H2S inhibitor dl-propargylglycine (PPG, 100 μM). The H2S donor NaHS and l-Cys, the substrate of endogenous H2S synthase, elicited similar responses to ACh and was inhibited by tetraethylamonine (1 mM) or PPG. ACh induces EDHF-mediated vasorelaxation and hyperpolarization in rat cerebral arteries. These responses are up-regulated by ischemia-reperfusion while NO-mediated responses are down-regulated. Further, the ACh-induced, EDHF-mediated relaxation, and hyperpolarization and the inhibition of these responses are similar to the H2S-induced responses, suggesting that H2S is a possible candidate for EDHF in rat cerebral vessels.

  16. Temporal profiles of age-dependent changes in cytokine mRNA expression and glial cell activation after status epilepticus in postnatal rat hippocampus

    Directory of Open Access Journals (Sweden)

    Ruohonen Saku

    2011-04-01

    Full Text Available Abstract Background Status epilepticus (SE is proposed to lead to an age-dependent acute activation of a repertoire of inflammatory processes, which may contribute to neuronal damage in the hippocampus. The extent and temporal profiles of activation of these processes are well known in the adult brain, but less so in the developing brain. We have now further elucidated to what extent inflammation is activated by SE by investigating the acute expression of several cytokines and subacute glial reactivity in the postnatal rat hippocampus. Methods SE was induced by an intraperitoneal (i.p. injection of kainic acid (KA in 9- and 21-day-old (P9 and P21 rats. The mRNA expression of interleukin-1 beta (IL-1β, tumor necrosis factor-alpha (TNF-α, interleukin-10 (IL-10, matrix metalloproteinase-9 (MMP-9, glial-derived neurotrophic factor (GDNF, interferon gamma (IFN-γ, and transforming growth factor-beta 1 (TGF-β1 were measured from 4 h up to 3 days after KA injection with real-time quantitative PCR (qPCR. IL-1β protein expression was studied with ELISA, GFAP expression with western blotting, and microglial and astrocyte morphology with immunohistochemistry 3 days after SE. Results SE increased mRNA expression of IL-1β, TNF-α and IL-10 mRNA in hippocampus of both P9 and P21 rats, their induction being more rapid and pronounced in P21 than in P9 rats. MMP-9 expression was augmented similarly in both age groups and GDNF expression augmented only in P21 rats, whereas neither IFN-γ nor TGF-β1 expression was induced in either age group. Microglia and astrocytes exhibited activated morphology in the hippocampus of P21 rats, but not in P9 rats 3 d after SE. Microglial activation was most pronounced in the CA1 region and also detected in the basomedial amygdala. Conclusion Our results suggest that SE provokes an age-specific cytokine expression in the acute phase, and age-specific glial cell activation in the subacute phase as verified now in the

  17. Exploration of dopamine transporter and D2 receptors in morphine dependent rats through 125I-β-CTT, 125I-IBZM cerebral autoradiography and the biodistribution study

    International Nuclear Information System (INIS)

    Objective: To explore the variation of cerebral dopamine (DA) transmitting system in morphine dependent (MD) rats using dopamine transporter (DAT) and D2 receptors imaging agent. Methods: MD model rats were established by using a two-compartment (C1 and C2-morphine conditioned compartment) apparatus for assessing morphine conditioned place preferences in rats. 125I-2β-carbomethoxy-3β-(4-iodophenyl) tropane (125I-β-CIT) and 125I-3-iodo-2-hydroxy-6-methoxy-N[(1-ethyl-2-pyrrolidinyl) methyl] benzamide (125I-IBZM) cerebral DAT and D2 receptor autoradiography and biodistribution study were used to evaluate the variation of DAT and D2 receptors in morphine dependent rats. Results: The mean time of MD rats entering from C1 to C2 was (0.84 +- 0.50) min after 6 days' conditioned place preference training, shorter than that of the control group [(2.40 +- 1.10) min, P 125I-β-CIT uptake ratio of striatum (ST)/cerebellum (CB) and nucleus acumens (NAC)/CB in MD group were 4.76 +- 0.92 and 2.72 +- 0.96, significantly lower than that of control group (5.92 +- 0.67 and 4.16 +- 0.56, P 125I-IBZM uptake ratio in MD group were 4.11 +- 0.56 and 2.64 +- 0.25, lower than that in control group (5.43 +- 0.74 and 3.49 +- 0.65, P 125I-β-CIT, 125I-IBZM biodistribution study also showed that the DAT and D2 binding sites were reduced in ST of MD group by (21.68 +- 11.11)% and (18.69 +- 9.97)% comparing to the controls, respectively. Conclusions: The DAT and D2 receptors in both ST and NAC were all involved and reduced to some extent in morphine dependent model rats, the DAT and D2 receptor imaging agent could reflect the variation of DAT and D2receptors, this would afford the theoretical basis for D2 receptors and DAT imaging in study on preventing drug addiction and on its abstinence

  18. Electroacupuncture inhibits apoptosis in annulus fibrosis cells through suppression of the mitochondria-dependent pathway in a rat model of cervical intervertebral disc degradation

    Directory of Open Access Journals (Sweden)

    Jun Liao

    2012-01-01

    Full Text Available The purpose of this study was to investigate whether treatment with electroacupuncture (EA inhibited mitochondria-dependent apoptosis in annulus fibrosis (AF cells in a rat model of cervical intervertebral disc degradation induced by unbalanced dynamic and static forces. Forty Sprague-Dawley rats were used in this study, of which 30 underwent surgery to induce cervical intervertebral disc degradation, 10 rats received EA at acupoints Dazhui (DU 14 and Shousanli (LI 10. TUNEL staining was measured to assess apoptosis in AF cells, immunohistochemistry was used to examine Bcl-2 and Bax expression, colorimetric assays were used to determine caspase 9 and caspase 3 activities and RT-PCR and western blotting were used to assess the mRNA and protein expression of Crk and ERK2. Treatment with EA reduced the number of AF-positive cells in TUNEL staining, increased Bcl-2-positive cells and decreased Bax-positive cells in immunohistochemical staining, significantly inhibited the activation of caspases-9 and -3, and enhanced the mRNA and protein expression of Crk and ERK2. Our data show that EA inhibits AF cell apoptosis via the mitochondria-dependent pathway and up-regulates Crk and ERK2 expression. These results suggest that treatment with may be a good alternative therapy for preventing cervical spondylosis.

  19. In vitro screening of reversible and time-dependent inhibition on CYP3A by TM208 and TM209 in rat liver microsomes

    Directory of Open Access Journals (Sweden)

    Miaoran Ning

    2012-04-01

    Full Text Available TM208 and TM209, dithiocarbamate derivatives with potential anti-cancer effects, were evaluated in reversible and time-dependent cytochrome P450 (CYP 3A inhibition assays in rat liver microsomes using testosterone as probe substrate. Both compounds were found to be weak reversible inhibitors and moderate mechanism-based inhibitors of rat CYP3A. For reversible inhibition on rat CYP3A, the Ki values of competitive inhibition model were 12.10±1.75 and 13.94±1.31 μM, respectively. For time-dependent inhibition, the inactivation constants (Kl were 31.93±12.64 and 32.91±15.58 μM, respectively, and the maximum inactivation rates (kinact were 0.03497±0.0069 and 0.07259±0.0172 min−1 respectively. These findings would provide useful in vitro information for future in vivo DDI studies on TM208 or TM209.

  20. The effects of intra-locus coeruleus injection of dopamine D2 receptor agents on Naloxone withdrawal signs in Morphine-dependent rats

    Directory of Open Access Journals (Sweden)

    Mirzaii Dizgah I

    2007-07-01

    Full Text Available Background: Opiate-induced addiction is a main social problem in Iran. As treatment of this problem is a health priority among the medical community, studies on this topic are very crucial. The exact mechanism of dependence on opiates and their withdrawal syndrome remain unclear. It seems that dopaminergic system and locus coeruleus (LC have an important role in the expression of somatic signs during opioids withdrawal. The LC has been shown to contain significant levels of dopamine (DA. In the present study, the effects of different D2 dopaminergic receptor agonist and antagonist administration in the LC on withdrawal sign expression in morphine dependence is investigated in rats. Methods: Adult male Wistar rats, weighing 220–280 g were divided into eight groups (n=8. Two cannulae were stereotaxically implanted bilaterally into the LC of each rat. After a one-week recovery, seven groups were rendered dependent on morphine by subcutaneous injection during a seven-day period. Non-dependent control animals received saline according to the same protocol. Animals received bilateral intra-LC injections of saline (1 μg/site and quinpirole (0.1, 0.3 and 0.5 μg/site, a D2 agonist 15 min and sulpiride (5, 15 and 30 μg/site, a D2 antagonist 30 min prior to naloxone injection about 24 hours after the last dose of morphine or saline according to their respective group. To calculate the total withdrawal score, as an index of withdrawal syndrome, 20 different withdrawal signs were assessed and the scores of the intensity of these withdrawal signs were added. Results: Total withdrawal scores were significantly decreased by quinpirole (0.1µg/site and sulpiride (15 and 30 µg/site. Conclusion: The D2 dopaminergic system in the LC may be involved in the morphine-induced dependency in rats. Further studies are needed to define the mechanism of this dependency in order to improve methods for the rehabilitation of addicts.

  1. In vitro formation of 25-hydroxyvitamin D3 metabolites in endometrium: dependence on the hormonal status of the rat.

    Science.gov (United States)

    Acker, G M; Garabedian, M; Guillozo, H; Pecquinot, M A; Balsan, S

    1982-12-01

    Rat myometrial tissue and endometrial cells were incubated with labeled 25-hydroxyvitamin D3 ([3H-26,27] 25OHD3) for 70 min at 37 C, and the resulting metabolites were isolated by sequential Sephadex LH-20 chromatography and high performance liquid chromatography. Two peaks more polar than 25OHD3 were present on the Sephadex LH-20 chromatograms. One of these metabolites had an identical chromatographic behavior on three different HPLC systems and an identical sensitivity to periodate cleavage as biosynthetic [3H-26,27] 24,25-dihydroxyvitamin D3 ([3H-26,27]24,25-(OH)2D3]. The in vitro production of this putative 24,25-(OH)2D3 was significantly higher in castrated animals than in normal adult rats. Treatment of rats with 17 beta-estradiol and/or medroxyprogesterone acetate reversed the effect of ovariectomy on 25OHD3 conversion. The in vitro production of the putative 24,25-(OH)2D3 was low during the estrous cycle and the initial stage of pregnancy. A dramatic increase in its production was observed on days 12 and 14 of pregnancy. 25OHD3 conversion was higher in endometrium than in myometrium under every experimental condition tested. These results demonstrate the ability of rat uterine tissue to convert 25OHD3 into more polar derivatives in vitro, and show the influence of the hormonal status of the rat on this in vitro capacity. PMID:6982812

  2. DOSE-DEPENDENT EFFECTS OF THE ANTIPROGESTIN, RU486, ON SEXUAL BEHAVIOR OF NATURALLY-CYCLING FISCHER RATS

    Science.gov (United States)

    Uphouse, Lynda

    2015-01-01

    Regularly cycling Fischer female rats were treated with either a low (5 mg/kg) or high (5 mg/RAT; approximately 30 mg/kg) dose of the antiprogestin, RU486, before the morning of proestrus or on the morning of proestrus. The emergence of sexual behavior after treatment with RU486 was examined in a mating test with a sexually active male rat. Lordosis behavior was remarkably resistant to the effects of RU486. Only the high dose of RU486 given the evening before proestrus, approximately 22 hours before mating, reduced lordosis behavior. Independent of dose or time of treatment, proceptivity was reduced and resistance to the male’s attempts to mount was increased by RU486 treatment. In addition, the effect of a 5 min restraint stress on sexual behavior was examined. In contrast to the relative resistance of lordosis behavior of unrestrained rats to RU486 treatment, RU486 treated rats showed a significant decline in lordosis behavior after restraint. These findings allow the suggestion that the emergence of lordosis behavior is relatively resistant to the antiprogestin while the maintenance of lordosis behavior after restraint may require participation of intracellular progesterone receptors. PMID:25591479

  3. Human T47D-ERβ breast cancer cells with tetracycline-dependent ERβ expression reflect ERα/ERβ ratios in rat and human breast tissue.

    Science.gov (United States)

    Evers, N M; van de Klundert, T M C; van Aesch, Y M; Wang, S; de Roos, W K; Romano, A; de Haan, L H J; Murk, A J; Ederveen, A G H; Rietjens, I M C M; Groten, J P

    2013-09-01

    T47D-ERβ breast cancer cells with tetracycline-dependent ERβ expression and constant ERα expression can be used to investigate effects of varying ERα/ERβ ratios on estrogen-induced cellular responses. This study defines conditions at which ERα/ERβ ratios in T47D-ERβ cells best mimic ERα/ERβ ratios in breast and other estrogen-sensitive tissues in vivo in rat as well as in human. Protein and mRNA levels of ERα and ERβ were analyzed in T47D-ERβ cells exposed to a range of tetracycline concentrations and compared to ERα and ERβ levels found in breast, prostate, and uterus from rat and human origin. The ERα/ERβ ratio in T47D-ERβ cells exposed to >150ng/ml tetracycline is comparable to the ratio found in rat mammary gland and in human breast tissue. The ERα/ERβ ratio of other estrogen-sensitive rat and human tissues can also be mimicked in T47D-ERβ cells. The ERα/ERβ ratio found in MCF-7 and native T47D breast cancer cell lines did not reflect ratios in analyzed rat and human tissues, which further supports the use of T47D-ERβ cells as model for estrogen-responsive tissues. Using 17β-estradiol and the T47D-ERβ cells under the conditions defined to mimic various tissues it could be demonstrated how these different tissues vary in their proliferative response. PMID:23680332

  4. Activation of the trigeminal α2-adrenoceptor produces sex-specific, estrogen dependent thermal antinociception and antihyperalgesia using an operant pain assay in the rat.

    Science.gov (United States)

    Nag, Subodh; Mokha, Sukhbir S

    2016-11-01

    Higher prevalence of several pain disorders in women and sexual dimorphism in G-protein coupled receptor-induced analgesia has been reported. We have previously shown that α2-adrenoceptor-induced antinociception is sex-specific and attenuated by estrogen in the female rat. However, this evidence was obtained using reflexive withdrawal-based nociceptive assays conducted on restrained animals that may not involve cerebral processing. Hence, we evaluated whether activation of the trigeminal α2-adrenoceptor produces sex-specific antinociceptive and antihyperalgesic effects in the orofacial region of the rat using a reward conflict-based operant paradigm in which animals must tolerate nociceptive thermal stimulation to be rewarded. Male and ovariectomized (OVX) Sprague-Dawley rats were implanted intracisternally with a PE10 cannula for drug injections. A group of OVX rats (OVX+E) was administered subcutaneously with estradiol 48h before the test. Effect of clonidine, an α2-adrenoceptor agonist, was determined on the operant pain assay using a fully automated Orofacial Pain Assessment Device. Number of spout licks, thermode contacts, and amount of reward intake were automatically recorded by the ANY-maze software. Using acute pain modeling, clonidine produced a dose-dependent increase in all three parameters in male and OVX groups, however, it was ineffective in the OVX+E group. Similarly, using inflammatory pain modeling, clonidine significantly increased these parameters in carrageenan-treated male and OVX groups but not in the OVX+E group. Thus, α2-adrenoceptor activation produces sex-specific antinociception and antihyperalgesia and estrogen attenuates these effects in female rats using an operant pain assay. These findings may help the discovery of effective analgesics for each sex. PMID:27506651

  5. [Activity of liver mitochondrial NAD+-dependent dehydrogenases of the krebs cycle in rats with acetaminophen-induced hepatitis developed under conditions of alimentary protein deficiency].

    Science.gov (United States)

    Voloshchuk, O N; Kopylchuk, G P

    2016-01-01

    Activity of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, malate dehydrogenase, and the NAD(+)/NADН ratio were studied in the liver mitochondrial fraction of rats with toxic hepatitis induced by acetaminophen under conditions of alimentary protein deprivation. Acetaminophen-induced hepatitis was characterized by a decrease of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase and malate dehydrogenase activities, while the mitochondrial NAD(+)/NADН ratio remained at the control level. Modeling of acetaminophen-induced hepatitis in rats with alimentary protein caused a more pronounced decrease in the activity of NAD(+)-dependent dehydrogenases studied and a 2.2-fold increase of the mitochondrial NAD(+)/NADН ratio. This suggests that alimentary protein deprivation potentiated drug-induced liver damage.

  6. Adolescent and adult rats differ in the amnesic effects of acute ethanol in two hippocampus-dependent tasks: Trace and contextual fear conditioning.

    Science.gov (United States)

    Hunt, Pamela S; Barnet, Robert C

    2016-02-01

    Experience-produced deficits in trace conditioning and context conditioning have been useful tools for examining the role of the hippocampus in learning. It has also been suggested that learning in these tasks is especially vulnerable to neurotoxic effects of alcohol during key developmental periods such as adolescence. In five experiments we systematically examined the presence and source of age-dependent vulnerability to the memory-disrupting effects of acute ethanol in trace conditioning and contextual fear conditioning. In Experiment 1a pre-training ethanol disrupted trace conditioning more strongly in adolescent (postnatal day, PD30-35) than adult rats (PD65-75). In Experiment 1b when pre-training ethanol was accompanied by pre-test ethanol no deficit in trace conditioning was observed in adolescents, suggesting that state-dependent retrieval failure mediated ethanol's disruption of trace conditioning at this age. Experiment 2a and b examined the effect of ethanol pretreatment on context conditioning. Here, adult but not adolescent rats were impaired in conditioned freezing to context cues. Experiment 2c explored state-dependency of this effect. Pre-training ethanol continued to disrupt context conditioning in adults even when ethanol was also administered prior to test. Collectively these findings reveal clear age-dependent and task-dependent vulnerabilities in ethanol's disruptive effects on hippocampus-dependent memory. Adolescents were more disrupted by ethanol in trace conditioning than adults, and adults were more disrupted by ethanol