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Sample records for aggravates experimental liver

  1. Inhibition of caspase-9 aggravates acute liver injury through suppression of cytoprotective autophagy

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    Guo, Rui; Lin, Bin; Pan, Jing Fei; Liong, Emily C.; Xu, Ai Min; Youdim, Moussa; Fung, Man Lung; So, Kwok Fai; Tipoe, George L.

    2016-01-01

    Acute liver disease is characterized by inflammation, oxidative stress and necrosis, which can greatly influence the long term clinical outcome and lead to liver failure or cancer. Here, we initially demonstrated the beneficial role of caspase-9-dependent autophagy in acute liver injury. Treatment with caspase-9 inhibitor z-LEHD-FMK in HepG2 cells, AML12 cells and C57BL/b6N mice exacerbated CCl4-induced acute hepatocellular damage, and also down-regulated autophagy markers expression levels, indicating that caspase-9 inhibition may aggravate acute liver damage by suppressing cytoprotective autophagy. CCl4 was used as an acute liver injury inducer which caused oxidative stress and apoptosis through up-regulation of HIF-1α, as well as triggered hepatic inflammation and necroptosis via TLR4/NF-κB pathway. Caspase-9 Thr125 site was firstly phosphorylated by ERK1/2 which subsequently activated the cytoprotective autophagy process to attenuate acute CCl4 injury. Caspase-9 inhibition further aggravated hepatic necroptosis through NF-κB expression, leading to increased pro-inflammatory mediators levels, suggesting a protective role of caspase-9-dependent autophagy in the inflammatory process as well as its possibility being a new therapeutic target for the treatment of acute liver injury. PMID:27580936

  2. Liver Cholesterol Overload Aggravates Obstructive Cholestasis by Inducing Oxidative Stress and Premature Death in Mice

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    Natalia Nuño-Lámbarri

    2016-01-01

    Full Text Available Nonalcoholic steatohepatitis is one of the leading causes of liver disease. Dietary factors determine the clinical presentation of steatohepatitis and can influence the progression of related diseases. Cholesterol has emerged as a critical player in the disease and hence consumption of cholesterol-enriched diets can lead to a progressive form of the disease. The aim was to investigate the impact of liver cholesterol overload on the progression of the obstructive cholestasis in mice subjected to bile duct ligation surgery. Mice were fed with a high cholesterol diet for two days and then were subjected to surgery procedure; histological, biochemical, and molecular analyses were conducted to address the effect of cholesterol in liver damage. Mice under the diet were more susceptible to damage. Results show that cholesterol fed mice exhibited increased apoptosis and oxidative stress as well as reduction in cell proliferation. Mortality following surgery was higher in HC fed mice. Liver cholesterol impairs the repair of liver during obstructive cholestasis and aggravates the disease with early fatal consequences; these effects were strongly associated with oxidative stress.

  3. Acrolein, a highly toxic aldehyde generated under oxidative stress in vivo, aggravates the mouse liver damage after acetaminophen overdose.

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    Arai, Tomoya; Koyama, Ryo; Yuasa, Makoto; Kitamura, Daisuke; Mizuta, Ryushin

    2014-01-01

    Although acetaminophen-induced liver injury in mice has been extensively studied as a model of human acute drug-induced hepatitis, the mechanism of liver injury remains unclear. Liver injury is believed to be initiated by metabolic conversion of acetaminophen to the highly reactive intermediate N-acetyl p-benzoquinoneimine, and is aggravated by subsequent oxidative stress via reactive oxygen species (ROS), including hydrogen peroxide (H2O2) and the hydroxyl radical (•OH). In this study, we found that a highly toxic unsaturated aldehyde acrolein, a byproduct of oxidative stress, has a major role in acetaminophen-induced liver injury. Acetaminophen administration in mice resulted in liver damage and increased acrolein-protein adduct formation. However, both of them were decreased by treatment with N-acetyl-L-cysteine (NAC) or sodium 2-mercaptoethanesulfonate (MESNA), two known acrolein scavengers. The specificity of NAC and MESNA was confirmed in cell culture, because acrolein toxicity, but not H2O2 or •OH toxicity, was inhibited by NAC and MESNA. These results suggest that acrolein may be more strongly correlated with acetaminophen-induced liver injury than ROS, and that acrolein produced by acetaminophen-induced oxidative stress can spread from dying cells at the primary injury site, causing damage to the adjacent cells and aggravating liver injury.

  4. A case of aggravation of hemolytic anemia, elevated liver enzymes and low platelet count syndrome after delivery

    Institute of Scientific and Technical Information of China (English)

    JIANG Yuan-hui; WANG Yong-qing; WANG Jing; YE Rong-hua

    2011-01-01

    Background Hemolytic anemia, elevated liver enzymes and low platelet count (HELLP) syndrome is a severe obstetric complication which usually resolves in most patients after delivery.Methods We report a rare case of aggravation of HELLP syndrome after delivery.Results The patient underwent the treatment for HELLP syndrome,.including glucocorticoid therapy. The symptoms of HELLP syndrome reappeared and became more severe than before the termination of pregnancy. The patient also had severe and persistent hypoproteinemia, hyponatremia and hypocalcemia.Conclusions HELLP syndrome is an acute and critical obstetric syndrome which can have heterogeneous presentations and variable prognosis. We should be fully aware of the diverse clinical characteristics of this condition.

  5. Macrophage migration inhibitory factor promotes cell death and aggravates neurologic deficits after experimental stroke.

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    Inácio, Ana R; Ruscher, Karsten; Leng, Lin; Bucala, Richard; Deierborg, Tomas

    2011-04-01

    Multiple mechanisms contribute to tissue demise and functional recovery after stroke. We studied the involvement of macrophage migration inhibitory factor (MIF) in cell death and development of neurologic deficits after experimental stroke. Macrophage migration inhibitory factor is upregulated in the brain after cerebral ischemia, and disruption of the Mif gene in mice leads to a smaller infarct volume and better sensory-motor function after transient middle cerebral artery occlusion (tMCAo). In mice subjected to tMCAo, we found that MIF accumulates in neurons of the peri-infarct region, particularly in cortical parvalbumin-positive interneurons. Likewise, in cultured cortical neurons exposed to oxygen and glucose deprivation, MIF levels increase, and inhibition of MIF by (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) protects against cell death. Deletion of MIF in Mif(-/-) mice does not affect interleukin-1β protein levels in the brain and serum after tMCAo. Furthermore, disruption of the Mif gene in mice does not affect CD68, but it is associated with higher galectin-3 immunoreactivity in the brain after tMCAo, suggesting that MIF affects the molecular/cellular composition of the macrophages/microglia response after experimental stroke. We conclude that MIF promotes neuronal death and aggravates neurologic deficits after experimental stroke, which implicates MIF in the pathogenesis of neuronal injury after stroke.

  6. Acetylcholinesterase (AChE inhibition aggravates fasting-induced triglyceride accumulation in the mouse liver

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    Shin-Ichi Yokota

    2014-01-01

    Full Text Available Although fasting induces hepatic triglyceride (TG accumulation in both rodents and humans, little is known about the underlying mechanism. Because parasympathetic nervous system activity tends to attenuate the secretion of very-low-density-lipoprotein-triglyceride (VLDL-TG and increase TG stores in the liver, and serum cholinesterase activity is elevated in fatty liver disease, the inhibition of the parasympathetic neurotransmitter acetylcholinesterase (AChE may have some influence on hepatic lipid metabolism. To assess the influence of AChE inhibition on lipid metabolism, the effect of physostigmine, an AChE inhibitor, on fasting-induced increase in liver TG was investigated in mice. In comparison with ad libitum-fed mice, 30 h fasting increased liver TG accumulation accompanied by a downregulation of sterol regulatory element-binding protein 1 (SREBP-1 and liver-fatty acid binding-protein (L-FABP. Physostigmine promoted the 30 h fasting-induced increase in liver TG levels in a dose-dependent manner, accompanied by a significant fall in plasma insulin levels, without a fall in plasma TG. Furthermore, physostigmine significantly attenuated the fasting-induced decrease of both mRNA and protein levels of SREBP-1 and L-FABP, and increased IRS-2 protein levels in the liver. The muscarinic receptor antagonist atropine blocked these effects of physostigmine on liver TG, serum insulin, and hepatic protein levels of SREBP-1 and L-FABP. These results demonstrate that AChE inhibition facilitated fasting-induced TG accumulation with up regulation of the hepatic L-FABP and SREBP-1 in mice, at least in part via the activation of muscarinic acetylcholine receptors. Our studies highlight the crucial role of parasympathetic regulation in fasting-induced TG accumulation, and may be an important source of information on the mechanism of hepatic disorders of lipid metabolism.

  7. Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease

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    Leung, Christopher; Herath, Chandana B; Jia, Zhiyuan; Andrikopoulos, Sof; Brown, Bronwyn E; Davies, Michael J; Rivera, Leni R; Furness, John B; Forbes, Josephine M; Angus, Peter W

    2016-01-01

    AIM To determine if manipulation of dietary advanced glycation end product (AGE), intake affects non-alcoholic fatty liver disease (NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol (HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mRNA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content (a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/- animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD. PMID:27672297

  8. Administration of Mycobacterium leprae rHsp65 aggravates experimental autoimmune uveitis in mice.

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    Eliana B Marengo

    Full Text Available The 60 kDa heat shock protein family, Hsp60, constitutes an abundant and highly conserved class of molecules that are highly expressed in chronic-inflammatory and autoimmune processes. Experimental autoimmune uveitis [EAU] is a T cell mediated intraocular inflammatory disease that resembles human uveitis. Mycobacterial and homologous Hsp60 peptides induces uveitis in rats, however their participation in aggravating the disease is poorly known. We here evaluate the effects of the Mycobacterium leprae Hsp65 in the development/progression of EAU and the autoimmune response against the eye through the induction of the endogenous disequilibrium by enhancing the entropy of the immunobiological system with the addition of homologous Hsp. B10.RIII mice were immunized subcutaneously with interphotoreceptor retinoid-binding protein [IRBP], followed by intraperitoneally inoculation of M. leprae recombinant Hsp65 [rHsp65]. We evaluated the proliferative response, cytokine production and the percentage of CD4(+IL-17(+, CD4(+IFN-gamma(+ and CD4(+Foxp3(+ cells ex vivo, by flow cytometry. Disease severity was determined by eye histological examination and serum levels of anti-IRBP and anti-Hsp60/65 measured by ELISA. EAU scores increased in the Hsp65 group and were associated with an expansion of CD4(+IFN-gamma(+ and CD4(+IL-17(+ T cells, corroborating with higher levels of IFN-gamma. Our data indicate that rHsp65 is one of the managers with a significant impact over the immune response during autoimmunity, skewing it to a pathogenic state, promoting both Th1 and Th17 commitment. It seems comprehensible that the specificity and primary function of Hsp60 molecules can be considered as a potential pathogenic factor acting as a whistleblower announcing chronic-inflammatory diseases progression.

  9. FR167653, a p38 mitogen-activated protein kinase inhibitor, aggravates experimental colitis in mice

    Institute of Scientific and Technical Information of China (English)

    Takashi Nishimura; Akira Andoh; Atsushi Nishida; Makoto Shioya; Yuhsuke Koizumi; Tomoyuki Tsujikawa; Yoshihide Fujiyama

    2008-01-01

    AIM: To investigate the effects of FR167653 on the development of dextran sulfate sodium (DSS)-induced colitis in mice.METHODS: BALB/c mice were fed rodent chow containing 3.5% (wt/wt) DSS. The recipient mice underwent intra-peritoneal injection of vehicles or FR167653 (30 mg/kg per day). The mice were sacrificed on day 14, and the degree of colitis was assessed. Immunohistochemical analyses for CD4+ T cell and F4/80+ macrophage infiltration were also performed. Mucosal o/tokine expression was analyzed by RT-PCR.RESULTS: The body weight loss was more apparent in the FR167653-treated DSS mice than in the vehicle-treated DSS mice. The colon length was shorter in the FR167653-treated DSS mice than in the vehicle-treated DSS mice. Disease activity index and histological colitis score were significantly higher in FR167653- than in vehicle-treated DSS animals. Microscopically, mucosal edema, cellular infiltration (CD4 T cells and F4/80 macrophages), and the disruption of the epithelium were much more severe in FR167653-treated mice than in controls. Mucosal mRNA expression for interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were found to be markedly reduced in FR167653-treated DSS mice.CONCLUSION: Treatment with FR167653 aggravated DSS colitis in mice. This effect was accompanied by a reduction of mucosal IL-1β and TNF-α expression, suggesting a role of p38 mitogen-activated protein kinase (MAPK)-mediated proinflammatory cytokine induction in host defense mechanisms.

  10. Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice

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    Gavito, Ana Luisa; Bautista, Dolores; Suarez, Juan; Badran, Samir; Arco, Rocío; Pavón, Francisco Javier; Serrano, Antonia; Rivera, Patricia; Decara, Juan; Cuesta, Antonio Luis; Rodríguez-de-Fonseca, Fernando

    2016-01-01

    High-fat diet-induced obesity (DIO) is associated with fatty liver and elevated IL-6 circulating levels. IL-6 administration in rodents has yielded contradictory results regarding its effects on steatosis progression. In some models of fatty liver disease, high doses of human IL-6 ameliorate the liver steatosis, whereas restoration of IL-6 in DIO IL-6-/- mice up-regulates hepatic lipogenic enzymes and aggravates steatosis. We further examined the effects of chronic low doses of murine IL-6 on hepatic lipid metabolism in WT mice in DIO. IL-6 was delivered twice daily in C57BL/6J DIO mice for 15 days. The status and expression of IL-6-signalling mediators and targets were investigated in relation to the steatosis and lipid content in blood and in liver. IL-6 administration in DIO mice markedly raised circulating levels of lipids, glucose and leptin, elevated fat liver content and aggravated steatosis. Under IL-6 treatment there was hepatic Stat3 activation and increased gene expression of Socs3 and Tnf-alpha whereas the gene expression of endogenous IL-6, IL-6-receptor, Stat3, Cpt1 and the enzymes involved in lipogenesis was suppressed. These data further implicate IL-6 in fatty liver disease modulation in the context of DIO, and indicate that continuous stimulation with IL-6 attenuates the IL-6-receptor response, which is associated with high serum levels of leptin, glucose and lipids, the lowering levels of lipogenic and Cpt1 hepatic enzymes and with increased Tnf-alpha hepatic expression, a scenario evoking that observed in IL-6-/- mice exposed to DIO and in obese Zucker rats. PMID:27333268

  11. Response to Comment on "Tissue Factor-Dependent Chemokine Production Aggravates Experimental Colitis"

    NARCIS (Netherlands)

    Queiroz, K.C.; Spek, C.A.

    2011-01-01

    In our recent work we utilized genetically modified mice to investigate the role of tissue factor (TF) in experimental colitis. We present evidence suggesting TF plays a detrimental role in this disease via signal transduction dependent KC production in colon epithelial cells, which provokes granulo

  12. Increase in hippocampal water diffusion and volume during experimental pneumococcal meningitis is aggravated by bacteremia

    DEFF Research Database (Denmark)

    Holler, Jon G; Brandt, Christian T; Leib, Stephen L;

    2014-01-01

    pneumococci. The study comprised of four experimental groups. I. Uninfected controls (n = 8); II. Meningitis (n = 11); III. Meningitis with early onset bacteremia by additional i.v. injection of live pneumococci (n = 10); IV. Meningitis with attenuated bacteremia by treatment with serotype-specific anti...

  13. Antibiotic-induced imbalances in gut microbiota aggravates cholesterol accumulation and liver injuries in rats fed a high-cholesterol diet.

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    Hu, Xu; Wang, Tao; Liang, Shan; Li, Wei; Wu, Xiaoli; Jin, Feng

    2015-11-01

    Increasing evidence suggests that maintenance of homeostasis between gut microbiota and host plays an important role in human health. Many diseases, such as those affecting the liver, have been linked to imbalances in gut microbial communities. However, it is not clear whether an imbalance in gut microbiota promotes the onset of liver injury or if the imbalance results from the pathological state. In the current study, antibiotics were used to disturb the gut microbiota of both rats fed a high-cholesterol diet and rats fed a normal diet (controls). The prevalence of Bacteroidetes and Firmicutes were reduced, and Proteobacteria was greatly increased in the guts of rats after antibiotic treatment. The antibiotic-induced perturbation of gut microbiota aggravated cholesterol accumulation and liver injury in rats fed a high-cholesterol diet. This may have been due to an increase in intestinal permeability and plasma lipopolysaccharide (LPS), which lead to an increase in LPS absorption and activation of TLR4 signaling, resulting in the synthesis of pro-inflammatory cytokines and chemokines in liver tissues. This study suggests that imbalances in gut microbiota may be a predisposing factor for the onset of metabolic diseases and liver injuries related to cholesterol and high-cholesterol diets. Modulation of gut microbiota could be a novel target for preventing cholesterol-related metabolic disorders.

  14. Macrophage migration inhibitory factor promotes cell death and aggravates neurologic deficits after experimental stroke

    OpenAIRE

    Inácio, Ana R; Ruscher, Karsten; Leng, Lin; Bucala, Richard; Deierborg, Tomas

    2010-01-01

    Multiple mechanisms contribute to tissue demise and functional recovery after stroke. We studied the involvement of macrophage migration inhibitory factor (MIF) in cell death and development of neurologic deficits after experimental stroke. Macrophage migration inhibitory factor is upregulated in the brain after cerebral ischemia, and disruption of the Mif gene in mice leads to a smaller infarct volume and better sensory-motor function after transient middle cerebral artery occlusion (tMCAo)....

  15. Bile salt toxicity aggravates cold ischemic injury of bile ducts after liver transplantation in Mdr2+/- mice

    NARCIS (Netherlands)

    Hoekstra, H; Porte, RJ; Tian, Y; Jochum, W; Stieger, B; Moritz, W; Slooff, MJH; Graf, R; Clavien, PA

    2006-01-01

    Intrahepatic bile duct strictures are a serious complication after orthotopic liver transplantation (OLT). We examined the role of endogenous bile salt toxicity in the pathogenesis of bile duct injury after OLT. Livers from wild-type mice and mice heterozygous for disruption of the multidrug resista

  16. The in-vivo use of superparamagnetic iron oxide nanoparticles to detect inflammation elicits a cytokine response but does not aggravate experimental arthritis.

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    Eline A Vermeij

    Full Text Available Superparamagnetic Iron Oxide Nanoparticles (SPION are used in diagnostic imaging of a variety of different diseases. For such in-vivo application, an additional coating with a polymer, for example polyvinyl alcohol (PVA, is needed to stabilize the SPION and prevent aggregation. As the particles are foreign to the body, reaction against the SPION could occur. In this study we investigated the effects that SPION may have on experimental arthritis after intra-articular (i.a. or intravenous (i.v. injection.PVA-coated SPION were injected either i.a. (6 or 24 μg iron or i.v. (100 μg or 1 mg iron into naïve Toll-like receptor-4 deficient (TLR4-/- or wild-type C57Bl/6 mice, or C57Bl/6 mice with antigen-induced arthritis. As control, some mice were injected with PVA or PBS. MR imaging was performed at 1 and 7 days after injection. Mice were sacrificed 2 hours and 1, 2, 7, 10 and 14 days after injection of the SPION, and RNA from synovium and liver was isolated for pro-inflammatory gene expression analysis. Serum cytokine measurements and whole knee joint histology were also performed.Injection of a high dose of SPION or PVA into naïve knee joints resulted in an immediate upregulation of pro-inflammatory gene expression in the synovium. A similar gene expression profile was observed after SPION or PVA injection into knee joints of TLR4-/- mice, indicating that this effect is not due to LPS contamination. Histological analysis of the knee joints also revealed synovial inflammation after SPION injection. Two hours after i.v. injection of SPION or PVA into naïve mice, an upregulation of pro-inflammatory gene expression was detected in the liver. Administration of SPION or PVA into arthritic mice via i.a. injection did not result in an upregulation in gene expression and also no additional effects were observed on histology. MR imaging and histology showed long-term retention of SPION in the inflamed joint. However, 14 days after the injections no long

  17. Deleted in liver cancer 2 (DLC2 was dispensable for development and its deficiency did not aggravate hepatocarcinogenesis.

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    Tai On Yau

    Full Text Available DLC2 (deleted in liver cancer 2, a Rho GTPase-activating protein, was previously shown to be underexpressed in human hepatocellular carcinoma and has tumor suppressor functions in cell culture models. We generated DLC2-deficient mice to investigate the tumor suppressor role of DLC2 in hepatocarcinogenesis and the function of DLC2 in vivo. In this study, we found that, unlike homologous DLC1, which is essential for embryonic development, DLC2 was dispensable for embryonic development and DLC2-deficient mice could survive to adulthood. We also did not observe a higher incidence of liver tumor formation or diethylnitrosamine (DEN-induced hepatocarcinogenesis in DLC2-deficient mice. However, we observed that DLC2-deficient mice were smaller and had less adipose tissue than the wild type mice. These phenotypes were not due to reduction of cell size or defect in adipogenesis, as observed in the 190B RhoGAP-deficient mouse model. Together, these results suggest that deficiency in DLC2 alone does not enhance hepatocarcinogenesis.

  18. Liver-specific deletion of the signal transducer and activator of transcription 5 gene aggravates fatty liver in response to a high-fat diet in mice.

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    Baik, Myunggi; Nam, Yoon Seok; Piao, Min Yu; Kang, Hyeok Joong; Park, Seung Ju; Lee, Jae-Hyuk

    2016-03-01

    Growth hormone (GH) signal is mediated by signal transducer and activator of transcription 5 (STAT5), which controls hepatic lipid metabolism. Nonalcoholic fatty liver disease (NAFLD) is clinically associated with a deficiency in GH. This study was performed to understand the role of local STAT5 signaling on hepatic lipid and glucose metabolism utilizing liver-specific STAT5 gene deletion (STAT5 LKO) mice under both normal diet and high-fat diet (HFD) feeding conditions. STAT5 LKO induced hepatic steatosis under HFD feeding, while this change was not observed in mice on normal diet. STAT5 LKO caused hyperglycemia, hyperinsulinemia, hyperleptinemia and elevated free fatty acid and cholesterol concentrations under HFD feeding but induced only hyperglycemia on normal diet. At the molecular level, STAT5 LKO up-regulated the expression of genes involved in lipid uptake (CD36), very low-density lipoprotein receptor (VLDLR), lipogenic stearoyl-CoA desaturase and adipogenic peroxisome proliferator-activated receptor gamma, in both diet groups. In response to HFD feeding, further increases in CD36 and VLDLR expression were found in STAT5 LKO mice. In conclusion, our study suggests that low STAT5 signaling on normal diet predisposes STAT5 LKO mice to early development of fatty liver by hyperglycemia and activation of lipid uptake and adipogenesis. A deficiency in STAT5 signaling under HFD feeding deregulates hepatic and body glucose and lipid metabolism, leading to the development of hepatic steatosis. Our study indicates that low STAT5 signaling, due to low GH secretion, may increase a chance for NAFLD development in elderly people.

  19. Development of Experimental Vaccines Against Liver Flukes.

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    Yap, Huan Yong; Smooker, Peter M

    2016-01-01

    A multitude of experimental vaccines have been developed against liver flukes in the past. However, there has yet to be the development of a commercial livestock vaccine. Reasons for this may be multiple, and include the lack of identification of the best antigen(s), or the immune response induced by those antigens not being appropriate in either magnitude or polarity (and therefore not protective). Cathepsin proteases are the major component of the excretory/secretory (ES) material of liver flukes in all stages of their life cycle in the definitive host and are the primary antigens of interest for the vaccine development in many studies. Hence, this chapter presents the methodologies of using cathepsin proteases as targeted antigens in recombinant protein and DNA vaccine development to engender protective immune responses against fasciolosis.First, the experimental vaccines developed in the past and the criteria of an effective vaccine for fasciolosis are briefly reviewed. Then flowcharts for recombinant protein vaccine and DNA vaccine development are presented, followed by the detailed materials and methodologies.

  20. Experimental study of bioartificial liver with cultured human liver cells

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    AIM To establish an extracorporeal bioartificial liver support system (EBLSS) using cultured human liver cells and to study its support effect for fulminant hepatic failure (FHF).METHODS The liver support experiment of EBLSS consisting of aggregates cultured human liver cells, hollow fiber bioreactor, and circulation unit was carried out in dizhepatic dogs.RESULTS The viability of isolated hepatocytes and nonparenchymal liver cells reached 96%. These cells were successfully cultured as multicellular spheroids with synthetic technique. The typical morphological appearance was retained up to the end of the artificial liver experiment. Compared with the control dogs treated with EBLSS without liver cells, the survival time of artificial liver support dogs was significantly prolonged. The changes of blood pressure, heart rate and ECG were slow. Both serum ammonia and lactate levels were significantly lowered at the 3rd h and 5th h. In addition, a good viability of human liver cells was noted after 5 h experiment.CONCLUSION EBLSS playing a metabolic role of cultured human hepatocytes, is capable of compensating the function of the liver, and could provide effective artificial liver support and therapy for patients with FHF.

  1. Deficiency of Nuclear Receptor Nur77 Aggravates Mouse Experimental Colitis by Increased NFκB Activity in Macrophages.

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    Anouk A J Hamers

    Full Text Available Nuclear receptor Nur77, also referred to as NR4A1 or TR3, plays an important role in innate and adaptive immunity. Nur77 is crucial in regulating the T helper 1/regulatory T-cell balance, is expressed in macrophages and drives M2 macrophage polarization. In this study we aimed to define the function of Nur77 in inflammatory bowel disease. In wild-type and Nur77-/- mice, colitis development was studied in dextran sodium sulphate (DSS- and 2,4,6-trinitrobenzene sulfonic acid (TNBS-induced models. To understand the underlying mechanism, Nur77 was overexpressed in macrophages and gut epithelial cells. Nur77 protein is expressed in colon tissues from Crohn's disease and Ulcerative colitis patients and colons from colitic mice in inflammatory cells and epithelium. In both mouse colitis models inflammation was increased in Nur77-/- mice. A higher neutrophil influx and enhanced IL-6, MCP-1 and KC production was observed in Nur77-deficient colons after DSS-treatment. TNBS-induced influx of T-cells and inflammatory monocytes into the colon was higher in Nur77-/- mice, along with increased expression of MCP-1, TNFα and IL-6, and decreased Foxp3 RNA expression, compared to wild-type mice. Overexpression of Nur77 in lipopolysaccharide activated RAW macrophages resulted in up-regulated IL-10 and downregulated TNFα, MIF-1 and MCP-1 mRNA expression through NFκB repression. Nur77 also strongly decreased expression of MCP-1, CXCL1, IL-8, MIP-1α and TNFα in gut epithelial Caco-2 cells. Nur77 overexpression suppresses the inflammatory status of both macrophages and gut epithelial cells and together with the in vivo mouse data this supports that Nur77 has a protective function in experimental colitis. These findings may have implications for development of novel targeted treatment strategies regarding inflammatory bowel disease and other inflammatory diseases.

  2. Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice

    DEFF Research Database (Denmark)

    Gavito, Ana Luisa; Bautista, Dolores; Suarez, Juan;

    2016-01-01

    High-fat diet-induced obesity (DIO) is associated with fatty liver and elevated IL-6 circulating levels. IL-6 administration in rodents has yielded contradictory results regarding its effects on steatosis progression. In some models of fatty liver disease, high doses of human IL-6 ameliorate the ...

  3. Experimental vascular graft for liver transplantation

    NARCIS (Netherlands)

    Kobori, L; Nemeth, T; Nemes, B; Dallos, G; Sotonyi, P; Fehervari, [No Value; Patonai, A; Slooff, MJH; Jaray, J; De Jong, KP

    2003-01-01

    Hepatic artery thrombosis is a major cause of graft failure in liver transplantation. Use of donor interponates are common, but results are controversial because of necrosis or thrombosis after rejection. Reperfusion injury, hypoxia and free radical production determinate the survival. The aim of th

  4. Transplantation of fetal liver epithelial progenitor cells ameliorates experimental liver fibrosis in mice

    Institute of Scientific and Technical Information of China (English)

    Jin-Fang Zheng; Li-Jian Liang; Chang-Xiong Wu; Jin-Song Chen; Zhen-Sheng Zhang

    2006-01-01

    AIM: To investigate the effect of transplanted fetal liver epithelial progenitor (FLEP) cells on liver fibrosis in mice.METHODS: FLEP cells were isolated from embryonal day (ED) 14 BALB/c mice and transplanted into female syngenic BALB/c mice (n = 60). After partial hepatectomy (PH), diethylnitrosamine (DEN) was administered to induce liver fibrosis. Controls received FLEP cells and non-supplemented drinking water, the model group received DEN-spiked water, and the experimental group received FLEP cells and DEN.Mice were killed after 1, 2, and 3 mo, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), and laminin (LN) in serum,and hydroxyproline (Hyp) content in liver were assessed.Alpha-smooth muscle actin (α-SMA) of liver was tested by immunohistochemistry. Transplanted male mice FLEP cells were identified by immunocytochemistry for sry (sex determination region for Y chromosome) protein.RESULTS: Serum ALT, AST, HA, and LN were markedly reduced by transplanted FLEP cells. Liver Hyp content and α-SMA staining in mice receiving FLEP cells were lower than that of the model group, which was consistent with altered liver pathology. Transplanted cells proliferated and differentiated into hepatocytes and bile duct epithelial cells with 30%-50% repopulation in the liver fibrosis induced by DEN after 3 mo.CONCLUSION: Transplanted FLEP cells proliferate and differentiate into hepatocytes and bile duct epithelial cells with high repopulation capacity in the fiberized liver induced by DEN, which restores liver function and reduces liver fibrosis.

  5. Experimental models of hepatotoxicity related to acute liver failure

    Science.gov (United States)

    Maes, Michaël; Vinken, Mathieu; Jaeschke, Hartmut

    2015-01-01

    Acute liver failure can be the consequence of various etiologies, with most cases arising from drug-induced hepatotoxicity in Western countries. Despite advances in this field, the management of acute liver failure continues to be one of the most challenging problems in clinical medicine. The availability of adequate experimental models is of crucial importance to provide a better understanding of this condition and to allow identification of novel drug targets, testing the efficacy of new therapeutic interventions and acting as models for assessing mechanisms of toxicity. Experimental models of hepatotoxicity related to acute liver failure rely on surgical procedures, chemical exposure or viral infection. Each of these models has a number of strengths and weaknesses. This paper specifically reviews commonly used chemical in vivo and in vitro models of hepatotoxicity associated with acute liver failure. PMID:26631581

  6. Hyperbaric oxygen therapy aggravates liver reperfusion injury in rats Oxigenoterapia hiperbárica agrava lesão de reperfusão hepática em ratos

    Directory of Open Access Journals (Sweden)

    Cristiano Xavier Lima

    2008-08-01

    Full Text Available PURPOSE: To evaluate the effects of hyperbaric oxygen (HO therapy in the protection against liver ischemia/reperfusion injury. METHODS: Thirty-two male Wistar rats were divided into four groups of eight animals each: group A - laparotomy and liver manipulation, group B - liver ischemia and reperfusion, group C - HO pretreatment for 60 min followed by liver ischemia and reperfusion, and group D - pretreatment with ambient air at 2.5 absolute atmospheres for 60 min followed by liver ischemia and reperfusion. Plasma was assayed for aspartate aminotransferase (AST, alanine aminotransferase (ALT and lactate dehydrogenase (LDH. Intra-arterial blood pressure was monitored continuously. Myeloperoxidase activity in the liver and lung was assessed 30 min after reperfusion. RESULTS: Plasma AST, ALT and LDH increased after reperfusion in all animals. Plasma ALT values and myeloperoxidase activity in the liver parenchyma were higher in HO-pretreated animals than in groups A, B and D. HO had a negative hemodynamic effect during liver reperfusion. CONCLUSION: Liver preconditioning with hyperbaric oxygen therapy aggravated liver ischemia/reperfusion injury in rats as demonstrated by plasma ALT and liver myeloperoxidase activity.OBJETIVO: Avaliar os efeitos da oxigenoterapia hiperbárica (OH como método preventivo da lesão de isquemia e reperfusão (LIR do fígado. MÉTODOS: Trinta e dois ratos machos Wistar foram distribuídos em quatro grupos de oito animais cada: A - laparotomia e manipulação hepática, B - isquemia e reperfusão hepática, C - pré-tratamento com OH por 60 minutos seguido de isquemia e reperfusão hepática e D - pré-tratamento com ar ambiente a 2,5 atmosferas absolutas por 60 minuto e isquemia e reperfusão hepática. Dosagens seriadas de AST, ALT e DHL foram realizadas. A pressão intra arterial foi monitorizada continuamente. O grau de infiltração leucocitária no fígado e pulmões foi inferido pela dosagem de mieloperoxidade

  7. Oxidative Stress and Pulmonary Changes in Experimental Liver Cirrhosis

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    Renata Salatti Ferrari

    2012-01-01

    Full Text Available The use of carbon tetrachloride (CCl4 in rats is an experimental model of hepatic tissue damage; which leads to fibrosis, and at the long term, cirrhosis. Cirrhosis is the consequence of progressive continued liver damage, it may be reversible when the damaging noxae have been withdrawn. The aim of this study is to evaluate the changes caused by cirrhosis in lung and liver, through the experimental model of intraperitoneal CCI4 administration. We used 18 male Wistar rats divided into three groups: control (CO and two groups divided by the time of cirrhosis induction by CCI4: G1 (11 weeks, G2 (16 weeks. We found significant increase of transaminase levels and lipid peroxidation (TBARS in liver and lung tissue and also increased antioxidant enzymes SOD and CAT, as well as the expression of TNF-α and IL-1β in the lung of cirrhotic animals. We observed changes in gas exchange in both cirrhotic groups. We can conclude that our model reproduces a model of liver cirrhosis, which causes alterations in the pulmonary system that leads to changes in gas exchange and size of pulmonary vessels.

  8. 高通量测序探讨胰腺炎加重肝损伤的研究%Through high-throughput sequencing technologies to explore the mechanism of pancreatitis aggravating liver damage

    Institute of Scientific and Technical Information of China (English)

    王谦; 白槟; 赵占伟; 余鹏飞; 郝一鸣; 邱兆岩; 郭敏; 冯全新; 刘朝旭

    2016-01-01

    目的 探讨急性胰腺炎(AP)加重肝脏损伤的机制.方法 将SD大鼠随机分为AP组和对照组(NC),采用牛磺胆酸钠逆行胰胆管注射的方法建立AP模型,造模后6h经下腔静脉采血,检测血清淀粉酶、脂肪酶水平、胰腺水含量,同时收集肝脏组织,用于提取RNA.通过转录组测序(RNA-seq)的方法分析AP加重肝损害的相关基因和通路改变.结果 AP组与NC组比,其血清淀粉酶[(8 964.65 ±401.23) U/L]和脂肪酶[(2350.00 ±201.90) U/L]含量明显上升(P<0.05);胰腺水含量AP组[(79.42±1.21)%]显著高于NC组[(70.14±1.02)%];RNA-seq结果显示两组间共有2 249个差异表达基因,其中564个表达上调,1 685个表达下调.京都基因与基因组百科全书(KEGG)通路富集结果由高到低为代谢通路、炎性因子通路、趋化因子通路、Toll样受体通路等.结论 AP可能通过炎性因子、Toll样受体(TLR)等通路介导了对肝脏的损伤.%Objective To explore the mechanism of acute pancrea titis (AP) aggravating liver damage.Methods SD rats were randomly divided into negative control (NC) and AP group.We use the method of sodium taurocholate retrograde pancreatic duct injection to establish the model of AP.After 6 h of anesthesia,the blood were collected from the inferior vena cava to detect the levels of serum amylase and lipase.The liver tissue was collected imnediately in order to extract total RNA.The genes and related pathways were analyzed by RNA-seq.Results Compared to NC group,the levels of serum amylase [(8 964.65 ±401.23) U/L] and lipase [(2 350.00 ± 201.90) U/L] were significantly higher in AP group (P <0.05);the pancreatic water content in AP group [(79.42 ± 1.21) %] were significantly higher than NC group [(70.14 ± 1.02) %];RNA-seq results showed that there were 2249 differently expressed genes between AP and NC group,among which 564 genes were up-regulated and 1685 genes were down-regulated.Kyoto gene and genome encyclopedia (KEGG

  9. Bone disorders in experimentally induced liver disease in growing rats

    Institute of Scientific and Technical Information of China (English)

    Viktória Ferencz; Ferenc Szalay; Csaba Horváth; Béla Kári; János Gaál; Szilvia Mészáros; Zsuzsanna Wolf; Dalma Hegedüs; Andrea Horváth; Anikó Folhoffer

    2005-01-01

    AIM: To investigate the change of bone parameters in a new model of experimentally induced liver cirrhosis and hepatocellular carcinoma (HCC) in growing rats.METHODS: Fischer-344 rats (n = 55) were used. Carbon tetrachloride (CCl4), phenobarbital (PB), and a single diethylnitrosamine (DEN) injection were used. Animals were killed at wk 8 and 16. Bone mineral content, femoral length, cortical index (quotient of cortical thickness and whole diameter) and ultimate bending load (Fmax)of the femora were determined. The results in animals treated with DEN+PB+CCl4 (DPC, n = 21) were compared to those in untreated animals (UNT,n = 14) and in control group treated only with DEN+PB (DP, n = 20).RESULTS: Fatty liver and cirrhosis developed in each DPC-treated rat at wk 8 and HCC was presented at wk 16. No skeletal changes were found in this group at wk 8,but each parameter was lower (P<0.05 for each) at wk 16 in comparison to the control group. Neither fatty liver nor cirrhosis was observed in DP-treated animals at any time point. Femoral length and Fmax values were higher (P<0.05 for both) in DP-treated animals at wk 8 compared to the UNT controls. However, no difference was found at wk 16.CONCLUSION: Experimental liver cirrhosis and HCC are accompanied with inhibited skeletal growth, reduced bone mass, and decreased mechanical resistance in growing rats. Our results are in concordance with the data of other studies using different animal models. A novel finding is the transiently accelerated skeletal growth and bone strength after a 8-wk long phenobarbital treatment following diethylnitrosamine injection.

  10. Experimental obstructive cholestasis: the wound-like inflammatory liver response

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    Aller María-Angeles

    2008-11-01

    Full Text Available Abstract Obstructive cholestasis causes hepatic cirrhosis and portal hypertension. The pathophysiological mechanisms involved in the development of liver disease are multiple and linked. We propose grouping these mechanisms according to the three phenotypes mainly expressed in the interstitial space in order to integrate them. Experimental extrahepatic cholestasis is the model most frequently used to study obstructive cholestasis. The early liver interstitial alterations described in these experimental models would produce an ischemia/reperfusion phenotype with oxidative and nitrosative stress. Then, the hyperexpression of a leukocytic phenotype, in which Kupffer cells and neutrophils participate, would induce enzymatic stress. And finally, an angiogenic phenotype, responsible for peribiliary plexus development with sinusoidal arterialization, occurs. In addition, an intense cholangiocyte proliferation, which acquires neuroendocrine abilities, stands out. This histopathological finding is also associated with fibrosis. It is proposed that the sequence of these inflammatory phenotypes, perhaps with a trophic meaning, ultimately produces a benign tumoral biliary process – although it poses severe hepatocytic insufficiency. Moreover, the persistence of this benign tumor disease would induce a higher degree of dedifferentiation and autonomy and, therefore, its malign degeneration.

  11. Aggravation of viral hepatitis by platelet-derived serotonin.

    Science.gov (United States)

    Lang, Philipp A; Contaldo, Claudio; Georgiev, Panco; El-Badry, Ashraf Mohammad; Recher, Mike; Kurrer, Michael; Cervantes-Barragan, Luisa; Ludewig, Burkhard; Calzascia, Thomas; Bolinger, Beatrice; Merkler, Doron; Odermatt, Bernhard; Bader, Michael; Graf, Rolf; Clavien, Pierre-Alain; Hegazy, Ahmed N; Löhning, Max; Harris, Nicola L; Ohashi, Pamela S; Hengartner, Hans; Zinkernagel, Rolf M; Lang, Karl S

    2008-07-01

    More than 500 million people worldwide are persistently infected with hepatitis B virus or hepatitis C virus. Although both viruses are poorly cytopathic, persistence of either virus carries a risk of chronic liver inflammation, potentially resulting in liver steatosis, liver cirrhosis, end-stage liver failure or hepatocellular carcinoma. Virus-specific T cells are a major determinant of the outcome of hepatitis, as they contribute to the early control of chronic hepatitis viruses, but they also mediate immunopathology during persistent virus infection. We have analyzed the role of platelet-derived vasoactive serotonin during virus-induced CD8(+) T cell-dependent immunopathological hepatitis in mice infected with the noncytopathic lymphocytic choriomeningitis virus. After virus infection, platelets were recruited to the liver, and their activation correlated with severely reduced sinusoidal microcirculation, delayed virus elimination and increased immunopathological liver cell damage. Lack of platelet-derived serotonin in serotonin-deficient mice normalized hepatic microcirculatory dysfunction, accelerated virus clearance in the liver and reduced CD8(+) T cell-dependent liver cell damage. In keeping with these observations, serotonin treatment of infected mice delayed entry of activated CD8(+) T cells into the liver, delayed virus control and aggravated immunopathological hepatitis. Thus, vasoactive serotonin supports virus persistence in the liver and aggravates virus-induced immunopathology.

  12. TRANSPLANTATION OF HEPATOCYTES AS THE METHOD OF TREATMENT OF LIVER FAILURE: EXPERIMENTAL AND CLINICAL EXPERIENCE

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    M. Y. Shagidulin

    2010-01-01

    Full Text Available For correction and treatment of liver failure before liver transplantation were proposed severe methods such as: extracorporal devices, transplantation of hepatocytes and implanted tissue-engineering units. The function of healthy hepatocytes presumes to stabilize the state of patients with chronic liver diseases and to wait a donor organ transplantation. In this review the results of experimental and clinical therapy of liver diseases by method of hepatocyte transplantation were summarized. 

  13. Experimental study of the intraoperative irradiation for liver cancer

    Energy Technology Data Exchange (ETDEWEB)

    Arii, S.; Takasan, H.; Takahashi, S. (Kyoto Univ. (Japan). Faculty of Medicine)

    1981-07-01

    The resectability rate of the liver cancer is very low. Especially, hepatoma is apt to combine cirrhosis and its curability is poor as compared with malignant neoplasma of other organs. Therefore, the development of more effective adjuvant therapy for liver cancer is desirable. We studied the possibility of intraoperative radiotherapy with electron beams of Betatron. At first, we examined the influence of 5000 rad irradiation to approximately 1/2 area of the liver on the aspect of the serological liver function and histology using the domestic rabbits. Following this experiment, we used V x 2 carcinoma transplanted into the livers of the rabbits as the simulation model of the human liver tumors and examined the effect of irradiation to the tumor and its surrounding liver tissue. Results 1. The rabbits irradiated with 5000 rad to approximately 1/2 area of the liver intraoperatively grew healthily without severe dysfunction of the liver. 2. On the histological examination, degeneration and necrosis of the parenchymal cells appeared at the small parts of the irradiated area at the earlier periods of irradiation, but the necrotic regions did not get wider in range. Subsequently, liver fibrosis progressed gradually. 3. Irradiation to the rabbits transplanted V x 2 carcinoma resulted in the prolongation of the life spans and the diminution of the tumors.

  14. Disturbance of hepatic and intestinal microcirculation in experimental liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Sasa-Marcel Maksan; Eduard Ryschich; Zilfi (U)lger; Martha Maria Gebhard; Jan Schmidt

    2005-01-01

    AIM: To analyze hepatic, mesenteric and mucosal microcirculation and leukocyte-endothelium interaction (LEI) in a rat model with liver cirrhosis.METHODS: Hepatic cirrhosis was induced in Wistar rats by gavage with carbon tetrachloride, and intravital videomicroscopy was performed in liver, mesentery and small intestine mucosa. Special emphasis is given on microcirculatory and morphometric changes during cirrhotic portal hypertension.RESULTS: LEI was influenced significantly in the cirrhotic liver but not in the gut. Blood flow measurement showed significant differences among liver, main mesenteric vessels and the mucosa. The results of our study indicate that liver cirrhosis leads to alterations in hepatic and mesenteric blood flow but not in mucosal blood flow.CONCLUSION: The enhanced inflammatory response in hepatic microvessels may be caused by a decrease of antithrombin Ⅲ levels and could be responsible for disturbances of organ pathology.

  15. Cerebral blood flow autoregulation in experimental liver failure

    DEFF Research Database (Denmark)

    Dethloff, T.J.; Larsen, F.S.; Knudsen, Gitte Moos

    2008-01-01

    Patients with acute liver failure (ALF) display impairment of cerebral blood flow (CBF) autoregulation, which may contribute to the development of fatal intracranial hypertension, but the pathophysiological mechanism remains unclear. In this study, we examined whether loss of liver mass causes...... impairment of CBF autoregulation. Four rat models were chosen, each representing different aspects of ALF: galactosamine (GlN) intoxication represented liver necrosis, 90% hepatectomy (PHx90) represented reduction in liver mass, portacaval anastomosis (PCA) represented shunting of blood....../toxins into the systemic circulation thus mimicking intrahepatic shunting in ALF, PCA+NH(3) provided information about the additional effects of hyperammonemia Rats were intubated and sedated with pentobarbital. We measured CBF with laser Doppler, intracranial pressure (ICP) was measured in the fossa posterior...

  16. Experimental modified orthotopic piggy-back liver autotransplantation

    Energy Technology Data Exchange (ETDEWEB)

    Roveda, L. [Oncologic Surgery, Cancer Center of Excellence Fond. ' T.Campanella' , Europa Avenue, Catanzaro CZ-88100 (Italy)], E-mail: roveda.l@libero.it; Zonta, A. [Department of Surgery, University of Pavia, PV 27100 (Italy); Staffieri, F. [Veterinary Surgery Unit, Department of Emergencies and Organs Transplantation, Faculty of Veterinary Medicine, SP per Casamassima km 3, Valenzano, BA 70010 (Italy); Timurian, D.; DiVenere, B. [Surgery ' Madonna delle Grazie' Hospital, Contrada Cattedra Ambulante, Matera, MT 75100 (Italy); Bakeine, G.J. [Laboratorio Nazionale di Tecnologie Avanzate e Nanoscienza (TASC), Basovizza, TR (Italy); Crovace, A. [Veterinary Surgery Unit, Department of Emergencies and Organs Transplantation, Faculty of Veterinary Medicine, SP per Casamassima km 3, Valenzano, BA 70010 (Italy); Prati, U. [Oncologic Surgery, Cancer Center of Excellence Fond. ' T.Campanella' , Europa Avenue, Catanzaro CZ-88100 (Italy)

    2009-07-15

    The classical orthotopic liver autotransplantation is a very challenging and time wasting technique; it includes the division of major hepatic vessels and choledocus, and subsequent reconnection by end to end anastomoses. The caval end to end anastomoses are the most difficult to be performed and the interposition of a prosthesis can be required. We adopted the classical orthotopic liver autotransplantation technique in 2 patients affected with diffused liver metastases from colorectal cancer, for extracorporeal neutron capture therapy (BNCT). The procedure required very long operating times and the extracorporeal circulation (ECC) set up; furthermore the vena cava reconstruction was performed by the interposition of a goretex-prosthesis. We propose a 'modified orthotopic piggy-back technique' to simplify liver reconnection and shorten the operating time. Materials and methods: The technique was developed in the swine (25 kg body weight), under general anaesthesia. We performed the resection of the retro-hepatic vena cava with preservation of the caval flow during the anhepatic phase, by interposing a goretex-prosthesis. The reconstruction of the vena cava was then performed by a side-to-side cava-prosthesis anastomosis with lateral clamping of the prosthesis. The procedure was then completed according to the classical technique of liver transplantation. Results: The mean time for VC reconstruction was 56 ({+-}10) min. and the mean time for side-to-side VC-prosthesis anastomosis was 13 ({+-}4) min. Conclusions: The 'modified orthotopic piggy-back technique' can simplify the reimplant of the liver during autotransplantation and shorten the operating time. Furthermore also the time of total extracorporeal circulation is reduced, as during the anhepatic phase and during the side-to-side cava-prosthesis anastomosis the flow in the inferior vena cava is uninterrupted.

  17. Liver mitochondrial dysfunction and oxidative stress in the pathogenesis of experimental nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    C.P.M.S. Oliveira

    2006-02-01

    Full Text Available Oxidative stress and hepatic mitochondria play a role in the pathogenesis of nonalcoholic fatty liver disease. The aim of the present study was to evaluate the role of hepatic mitochondrial dysfunction and oxidative stress in the pathogenesis of the disease. Fatty liver was induced in Wistar rats with a choline-deficient diet (CD; N = 7 or a high-fat diet enriched with PUFAs-omega-3 (H; N = 7 for 4 weeks. The control group (N = 7 was fed a standard diet. Liver mitochondrial oxidation and phosphorylation were measured polarographically and oxidative stress was estimated on the basis of malondialdehyde and glutathione concentrations. Moderate macrovacuolar liver steatosis was observed in the CD group and mild liver steatosis was observed in the periportal area in the H group. There was an increase in the oxygen consumption rate by liver mitochondria in respiratory state 4 (S4 and a decrease in respiratory control rate (RCR in the CD group (S4: 32.70 ± 3.35; RCR: 2.55 ± 0.15 ng atoms of O2 min-1 mg protein-1 when compared to the H and control groups (S4: 23.09 ± 1.53, 17.04 ± 2.03, RCR: 3.15 ± 0.15, 3.68 ± 0.15 ng atoms of O2 min-1 mg protein-1, respectively, P < 0.05. Hepatic lipoperoxide concentrations were significantly increased and the concentration of reduced glutathione was significantly reduced in the CD group. A choline-deficient diet causes moderate steatosis with disruption of liver mitochondrial function and increased oxidative stress. These data suggest that lipid peroxidation products can impair the flow of electrons along the respiratory chain, causing overreduction of respiratory chain components and enhanced mitochondrial reactive oxygen species. These findings are important in the pathogenesis of nonalcoholic fatty liver disease.

  18. Liver mitochondrial dysfunction and oxidative stress in the pathogenesis of experimental nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Oliveira C.P.M.S.

    2006-01-01

    Full Text Available Oxidative stress and hepatic mitochondria play a role in the pathogenesis of nonalcoholic fatty liver disease. The aim of the present study was to evaluate the role of hepatic mitochondrial dysfunction and oxidative stress in the pathogenesis of the disease. Fatty liver was induced in Wistar rats with a choline-deficient diet (CD; N = 7 or a high-fat diet enriched with PUFAs-omega-3 (H; N = 7 for 4 weeks. The control group (N = 7 was fed a standard diet. Liver mitochondrial oxidation and phosphorylation were measured polarographically and oxidative stress was estimated on the basis of malondialdehyde and glutathione concentrations. Moderate macrovacuolar liver steatosis was observed in the CD group and mild liver steatosis was observed in the periportal area in the H group. There was an increase in the oxygen consumption rate by liver mitochondria in respiratory state 4 (S4 and a decrease in respiratory control rate (RCR in the CD group (S4: 32.70 ± 3.35; RCR: 2.55 ± 0.15 ng atoms of O2 min-1 mg protein-1 when compared to the H and control groups (S4: 23.09 ± 1.53, 17.04 ± 2.03, RCR: 3.15 ± 0.15, 3.68 ± 0.15 ng atoms of O2 min-1 mg protein-1, respectively, P < 0.05. Hepatic lipoperoxide concentrations were significantly increased and the concentration of reduced glutathione was significantly reduced in the CD group. A choline-deficient diet causes moderate steatosis with disruption of liver mitochondrial function and increased oxidative stress. These data suggest that lipid peroxidation products can impair the flow of electrons along the respiratory chain, causing overreduction of respiratory chain components and enhanced mitochondrial reactive oxygen species. These findings are important in the pathogenesis of nonalcoholic fatty liver disease.

  19. Experimental study of osthole on treatment of hyperlipidemic and alcoholic fatty liver in animals

    Institute of Scientific and Technical Information of China (English)

    Fang Song; Mei-Lin Xie; Lu-Jia Zhu; Ke-Ping Zhang; Jie Xue; Zhen-Lun Gu

    2006-01-01

    AIM: To evaluate the effects of osthole on fatty liver,and investigate the possible mechanism.METHODS: A quail model with hyperlipidemic fatty liver and rat model with alcoholic fatty liver were set up by feeding high fat diet and alcohol, respectively. These experimental animals were then treated with osthole 5-20 mg/kg for 6 wk, respectively. Whereafter, the lipid in serum and hepatic tissue, and coefficient of hepatic weight were measured.RESULTS: After treatment with osthole the levels of serum total cholesterol (TC), triglyceride (TG), lower density lipoprotein-cholesterol (LDL-C), coefficient of hepatic weight, and the hepatic tissue contents of TC and TG were significantly decreased. The activity of superoxide dismutase (SOD) in liver was improved.In alcohol-induced fatty liver rats, the level of malondialdehyde (MDA) in liver was decreased. In high fat-induced fatty liver quails, glutathione peroxidase (GSH-PX) in liver was significantly improved. The histological evaluation of liver specimens demonstrated that the osthole dramatically decreased lipid accumulation.CONCLUSION: These results suggested that osthole had therapeutic effects on both alcohol and high fatinduced fatty liver. The mechanism might be associated with its antioxidation.

  20. Aggravation of nonalcoholic steatohepatitis by moderate alcohol consumption is associated with decreased SIRT1 activity in rats

    Science.gov (United States)

    Chronic alcohol intake decreases adiponectin and sirtuin 1 (SIRT1) expressions, both of which have been implicated in various biological processes including inflammation, apoptosis and metabolism. We have previously shown that moderate consumption of alcohol aggravates liver inflammation and apoptos...

  1. The effects of aqueous extracts prepared from the leaves of Pistacia lentiscus in experimental liver disease.

    Science.gov (United States)

    Ljubuncic, Predrag; Song, Hui; Cogan, Uri; Azaizeh, Hassan; Bomzon, Arieh

    2005-08-22

    In a previous study, we identified Pistacia lentiscus was worthy for further laboratory evaluation because an aqueous extract of the plant suppressed iron-induced lipid peroxidation in rat liver homogenates without affecting mitochondrial respiration in cultured HepG2 and PC12 cells. The present study was undertaken to evaluate the efficacy of an aqueous extract prepared from the dried leaves of Pistacia lentiscus in a rat model of hepatic injury caused by the hepatotoxin, thioacetamide. We assessed the impact of daily dosing on biochemical and morphological indices and the extent of oxidative stress in the livers of healthy and thioacetamide-treated rats. In healthy rats, long-term administration of the extract induced hepatic fibrosis and an inflammatory response, mild cholestasis and depletion of reduced glutathione associated with an increase in its oxidized form. In thioacetamide-treated rats, long-term administration of extract aggravated the inflammatory and fibrotic and glutathione depleting responses without affecting the extent of lipid peroxidation. Although our previous in vitro study established that extracts prepared from the leaves of Pistacia lentiscus had antioxidant activity, this in vivo study establishes these extracts also contains hepatotoxins whose identity may be quite different from those compounds with antioxidant properties. The results of this study suggest complementing in vitro experiments with those involving animals are essential steps in establishing the safety of medicinal plants. Furthermore, these data confirm that complete reliance on data obtained using in vitro methodologies may lead to erroneous conclusions pertaining to the safety of phytopharmaceuticals.

  2. Iodine-125 interstitial brachytherapy for experimental liver cancer

    Institute of Scientific and Technical Information of China (English)

    ZHOU Fei-guo; YAN Jian-jun; HUANG Liang; LIU Cai-feng; ZHANG Xiang-hua; ZHOU Wei-ping; YAN Yi-qun

    2007-01-01

    Objective:To study the effect of iodine-125 interstitial brachytherapy on liver cancer.Methods:Animal model of human liver cancer was established by injecting SMMC-7721 cells cultivated in vitro subcutaneously into the flank of BALB/c nude mice.Nude mice with tumor of 5 mm in diameter were randomly divided into 2 groups(n=10).One iodine-125 seed of apparent activity 0.8 mCi was implanted into the center of tumor in treatment group,whereas an inactive seed was implanted in control group.The other 20 nude mice with tumor reaching 10 mm in diameter were also treated as above.The size of tumor was determined weekly after implantation,and pathological examination and blood routine were taken on the 28th day.Results:Tumor growth was obviously inhibited in treatment group of tumor of 5 mm in diameter,and there was statistically significant difference in tumor volume between treatment and control groups(P<0.01).Around iodine-125 seed,apparent necrosis of tumor was shown in treatment group,accompanied by karyopyknosis and reduced plasma in residual tumor cells microscopically.Tumor growth was not inhibited in either treatment or control group of tumor of 10 mm in diameter.There was no obvious adverse effect except for decreased white blood cells in treatment groups.Conclusion:There is certain effect of iodine-125 interstitial brachytherapy on liver cancer,which is associated with the size of tumor.

  3. A simplified experimental model of large-for-size liver transplantation in pigs

    Directory of Open Access Journals (Sweden)

    Antonio Jose Goncalves Leal

    2013-01-01

    Full Text Available OBJECTIVE: The ideal ratio between liver graft mass and recipient body weight for liver transplantation in small infants is unknown; however, if this ratio is over 4%, a condition called large-for-size may occur. Experimental models of large-for-size liver transplants have not been described in the literature. In addition, orthotopic liver transplantation is marked by high morbidity and mortality rates in animals due to the clamping of the venous splanchnic system. Therefore, the objective of this study was to create a porcine model of large-for-size liver transplantation with clamping of the supraceliac aorta during the anhepatic phase as an alternative to venovenous bypass. METHOD: Fourteen pigs underwent liver transplantation with whole-liver grafts without venovenous bypass and were divided into two experimental groups: the control group, in which the weights of the donors were similar to the weights of the recipients; and the large-for-size group, in which the weights of the donors were nearly 2 times the weights of the recipients. Hemodynamic data, the results of serum biochemical analyses and histological examination of the transplanted livers were collected. RESULTS: The mortality rate in both groups was 16.5% (1/7. The animals in the large-for-size group had increased serum levels of potassium, sodium, aspartate aminotransferase and alanine aminotransferase after graft reperfusion. The histological analyses revealed that there were no significant differences between the groups. CONCLUSION: This transplant method is a feasible experimental model of large-for-size liver transplantation.

  4. Treatment modalities in experimentally induced acute liver failure

    NARCIS (Netherlands)

    P.T. Ernst

    1988-01-01

    textabstractThe findings made in the presented study suggest that one or more still unknown factors inherent in the experimental models currently in use are of critical importance and that only a certain limited type of model of acute hepatic failure is suitable for the evaluation of the effectivene

  5. Boron neutron capture therapy (BNCT) for liver metastasis: therapeutic efficacy in an experimental model

    Energy Technology Data Exchange (ETDEWEB)

    David W. Nigg

    2012-08-01

    Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. The present study evaluates tumor control and potential radiotoxicity of BNCT in an experimental model of liver metastasis. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA–BNCT, boronophenylalanine (BPA) ? neutron irradiation; Beam only, neutron irradiation; Sham, matched manipulation. The total absorbed dose administered with BPA–BNCT was 13 ± 3 Gy in tumor and 9 ± 2 Gy in healthy liver. Three weeks posttreatment, the tumor surface area post-treatment/pre-treatment ratio was 0.46 ± 0.20 for BPA–BNCT, 2.7 ± 1.8 for Beam only and 4.5 ± 3.1 for Sham. The pre-treatment tumor nodule mass of 48 ± 19 mgfell significantly to 19 ± 16 mg for BPA–BNCT, but rose significantly to 140 ± 106 mg for Beam only and to 346 ± 302 mg for Sham. For both end points, the differences between the BPA–BNCT group and each of the other groups were statistically significant (ANOVA). No clinical, macroscopic or histological normal liver radiotoxicity was observed. It is concluded that BPA– BNCT induced a significant remission of experimental colorectal tumor nodules in liver with no contributory liver toxicity.

  6. Peroxisome proliferator activated receptor-γ in pathogenesis of experimental fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Cai-Yan Zhao; Ling-Ling Jiang; Li Li; Zhuo-Jun Deng; Bao-Li Liang; Jian-Mei Li

    2004-01-01

    AIM: To study the expression of peroxisome proliferator activated receptor-γ (PPARγ) in the liver of rats with fatty liver disease (FLD) and to explore the role of PPARγ in the pathogenesis of FLD to provide the basis for using PPARγligand to treat patients with FLD.METHODS: Forty Wistar rats were divided into 4 groups of ten rats each randomly: normal group (group A), alcohol group (group B), fat-rich diet group (group C), alcohol and fat-rich diet group (group D). The rats were sacrificed at the end of the 16th week from the feeding day. Alanine aminotransferase (ALT), tumor necrosis factor-alfa (TNFα)in serum and malondialdehyde (MDA) in liver homogenate were determined; livers were collected for observing pathologic changes by HE, Sudan Ⅳ, Masson stain under microscope. The morphologic results were analyzed by picture quantitative analysis technique. The changes of ultrastructure were also examined under electron microscope.The expression of PPARγ in liver was detected by immunohistochemistry and RT-PCR. The correlations between the expression of PPARγ and biochemical indexes, and liver histology were analyzed.RESULTS: The steatosis, inflammation, necrosis and fibrosis were present in livers of different experimental groups,especially in livers of alcohol and fat-rich diet group. The content of immunodetectable PPARγ was decreasedremarkably in the livers of model rats (group B-D); the level in alcohol and fat-rich diet group (3.43±1.48) was significantly lower than that in normal group (18.34±3.73), alcohol group (8.82±2.52) and fat-rich diet group (11.73±2.51) (all P<0.01).The level of PPARγ mRNA was also lower in the livers of model rats (group B-D) than in'livers of controls. The expression of PPARγ in rat liver correlated negatively with the degree of its inflammation, necrosis and fibrosis, as well as the level of serum TNFα and the content of MDA in liver homogenates, but not with steatosis or serum ALT.CONCLUSION: Decreased expression

  7. Moderate alcohol consumption aggravates high fat-diet induced steatohepatitis in rats

    Science.gov (United States)

    Background: Nonalcoholic steatohepatitis (NASH) develops in the absence of chronic and excessive alcohol consumption. However, it remains unknown whether moderate alcohol consumption aggravates liver inflammation in pre-existing NASH condition. Methods: Sprague-Dawley rats were first fed ad libitum...

  8. Influence of experimental conditions on data variability in the liver comet assay.

    Science.gov (United States)

    Guérard, M; Marchand, C; Plappert-Helbig, U

    2014-03-01

    The in vivo comet assay has increasingly been used for regulatory genotoxicity testing in recent years. While it has been demonstrated that the experimental execution of the assay, for example, electrophoresis or scoring, can have a strong impact on the results; little is known on how initial steps, that is, from tissue sampling during necropsy up to slide preparation, can influence the comet assay results. Therefore, we investigated which of the multitude of steps in processing the liver for the comet assay are most critical. All together eight parameters were assessed by using liver samples of untreated animals. In addition, two of those parameters (temperature and storage time of liver before embedding into agarose) were further investigated in animals given a single oral dose of ethyl methanesulfonate at dose levels of 50, 100, and 200 mg/kg, 3 hr prior to necropsy. The results showed that sample cooling emerged as the predominant influence factor, whereas variations in other elements of the procedure (e.g., size of the liver piece sampled, time needed to process the liver tissue post-mortem, agarose temperature, or time of lysis) seem to be of little relevance. Storing of liver samples of up to 6 hr under cooled conditions did not cause an increase in tail intensity. In contrast, storing the tissue at room temperature, resulted in a considerable time-dependent increase in comet parameters.

  9. Experimental models for induction of liver cirrhosis in animals: a review

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    Cristiane Carlin Passos

    2010-06-01

    Full Text Available The liver plays a key role in the homeostatic balance of many biological processes. Cirrhosis is a syndrome in which chronic liver diseases converge, leading to hepatocellular injury, the exacerbated deposition of fibrous tissue, and eventually the disruption of the tissue architecture. The liver is subject to potential injury by a large quantity of pharmacological agents, toxic and/or microbiological. For the study of possible treatments for cirrhosis, it is necessary to establish animal models of induction of cirrhosis, especially in laboratory rodents which mimic the cirrhotic process found in animals and humans, that have high reproducibility and uniformity, with a low mortality rate. Thus, the induction of liver cirrhosis becomes essential to the investigation of chronic liver diseases, as well as to test possible therapeutic treatments for subsequent use in human and veterinary clinics. Currently, experimental studies have been conducted to collect data about the various hepatotoxic drug effects. Carbon tetrachloride -CCl4, Thioacetamide –TAA and dimethylnitrosamine -DMN were the drugs of choice for cirrhosis induction in experimental models in this study. The model using cirrhotic TAA seems to be the best model for the reason that it produces a histological pattern closest to that of human cirrhosis, leading to lower mortality with higher reproducibility and security, despite the longer period of induction (14 weeks.

  10. LUNG AND LIVER CHANGES DUE TO THE INDUCTION OF CIRRHOSIS IN TWO EXPERIMENTAL MODELS

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    Renata Salatti FERRARI

    2013-09-01

    Full Text Available Context To evaluate lung and liver changes in two experimental models using intraperitoneal carbon tetrachloride (CCl4 and bile duct ligation (BDL. Methods Twenty-four male Wistar rats were divided into a control group (CO and an experimental group (EX. We evaluated the liver transaminases (AST, ALT, AP, arterial blood gases (PaO2, PCO2 and SpO2 and lipid peroxidation by TBARS (substances that react to thiobarbituric acid and chemiluminescence. We also evaluated the antioxidant enzyme superoxide dismutase (SOD and histology of lung tissue and liver. Results There were significant differences in AST, ALT, ALP and PaO2 between CO group and EX group (P<0.05. The levels of TBARS, chemiluminescence and activity of enzyme superoxide dismutase were increased to different degrees in the CCl4 groups: CO and in the BDL -EX (P<0.05, respectively. In the lung histology, an increase in the wall thickness of the pulmonary artery and a diameter reduction in the CCl4 animal model were observed: comparing CO group with EX group, we observed a reduction in thickness and an increase in the diameter of the artery wall lung. Conclusion Both experimental models have caused liver damage and alterations in the artery wall that are associated with major changes in pulmonary gas exchange.

  11. Therapeutic effect of Pleurotus eryngii cellulose on experimental fatty liver in rats.

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    Huang, J F; Zhan, T; Yu, X L; He, Q A; Huang, W J; Lin, L Z; Du, Y T; Pan, Y T

    2016-02-26

    The aim of this study was to explore the therapeutic effect of Pleurotus eryngii cellulose on experimental fatty liver in rats. Rats were fed high-fat fodder to establish a rat fatty liver model, and were then fed different concentrations of Pleurotus eryngii cellulose for six weeks. Lipitor was used as a positive control. Measured levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and total triglyceride (TG); the activity of malondialdehyde (MDA), superoxide dismutase (SOD), hepatic lipase (HL), and lipoprotein lipase; and liver histopathological changes. Successfully established rat fatty liver model after feeding high-fat fodder for one week. A diet of P. eryngii cellulose for six weeks significantly reduced ALT, AST, TC, and TG levels in rat serum (P 0.05). SOD activity increased significantly, while MDA and HL activity decreased (P < 0.05); fatty degeneration and fat accumulation both decreased in hepatic tissue. Hepatic protection of P. eryngii cellulose showed dose-related effect. P. eryngii cellulose can affect lipid metabolism, having therapeutic effects on fatty liver in rats.

  12. ATRA inhibits experimental liver metastasis of gastric cancer cells in nude mice

    Institute of Scientific and Technical Information of China (English)

    Yu Qiang Chen; Qiao Wu; Zheng Ming Chen; Fu Chen; Wen Jin Su

    2000-01-01

    AIM To study the effects of ATRA on experimental liver metastasis of gastric cancer cells.METHODS MGc80-3 and SGC-7901 cells were injectied into spleen subcapsule of nude mice, who weresubsequently administrated with ATRA every other day. Food-intake and body weight of mice were measuredweekly. After six weeks, the nude mice were executed, tumors in spleen and liver were examinedpathologically, microtumor vessel density (MVD) was accounted by immunohistochemical method and serumCEA was measured by radioimmunoassay.RESULTS Nude mice administrated with ATRA, the growth of spleen tumor and its metastatic ability toliver were inhibited, the metastatic rate was decreased by 33.3% (MGc80-3) and 50.0% (SGC-7901). SpleenMVD and liver MVD were reduced by 28.6% and 22.9% (MGc80-3), 23.7% and 37.6% (SGC-7901),respectively. The serum CEA was lowered by 43.4% (MGc80-3).CONCLUSION ATRA can effectively inhibit the experimental liver metastasis of gastric cancer cells,which is relavant with the decrease of MVD and CEA.

  13. Ultrasound imaging in an experimental model of fatty liver disease and cirrhosis in rats

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    Campos de Carvalho Antonio

    2010-01-01

    Full Text Available Abstract Background Domestic dogs and cats are very well known to develop chronic hepatic diseases, including hepatic lipidosis and cirrhosis. Ultrasonographic examination is extensively used to detect them. However, there are still few reports on the use of the ultrasound B-mode scan in correlation with histological findings to evaluate diffuse hepatic changes in rodents, which represent the most important animal group used in experimental models of liver diseases. The purpose of this study was to determine the reliability of ultrasound findings in the assessment of fatty liver disease and cirrhosis when compared to histological results in Wistar rats by following up a murine model of chronic hepatic disease. Results Forty Wistar rats (30 treated, 10 controls were included. Liver injury was induced by dual exposure to CCl4 and ethanol for 4, 8 and 15 weeks. Liver echogenicity, its correlation to the right renal cortex echogenicity, measurement of portal vein diameter (PVD and the presence of ascites were evaluated and compared to histological findings of hepatic steatosis and cirrhosis. Liver echogenicity correlated to hepatic steatosis when it was greater or equal to the right renal cortex echogenicity, with a sensitivity of 90%, specificity of 100%, positive and negative predictive values of 100% and 76.9% respectively, and accuracy of 92.5%. Findings of heterogeneous liver echogenicity and irregular surface correlated to liver cirrhosis with a sensitivity of 70.6%, specificity of 100%, positive and negative predictive values of 100% and 82.1% respectively, and accuracy of 87.5%. PVD was significantly increased in both steatotic and cirrhotic rats; however, the later had greater diameters. PVD cut-off point separating steatosis from cirrhosis was 2.1 mm (sensitivity of 100% and specificity of 90.5%. One third of cirrhotic rats presented with ascites. Conclusion The use of ultrasound imaging in the follow-up of murine diffuse liver disease

  14. In situ metabolic flux analysis to quantify the liver metabolic response to experimental burn injury.

    Science.gov (United States)

    Izamis, Maria-Louisa; Sharma, Nripen S; Uygun, Basak; Bieganski, Robert; Saeidi, Nima; Nahmias, Yaakov; Uygun, Korkut; Yarmush, Martin L; Berthiaume, Francois

    2011-04-01

    Trauma such as burns induces a hypermetabolic response associated with altered central carbon and nitrogen metabolism. The liver plays a key role in these metabolic changes; however, studies to date have evaluated the metabolic state of liver using ex vivo perfusions or isotope labeling techniques targeted to specific pathways. Herein, we developed a unique mass balance approach to characterize the metabolic state of the liver in situ, and used it to quantify the metabolic changes to experimental burn injury in rats. Rats received a sham (control uninjured), 20% or 40% total body surface area (TBSA) scald burn, and were allowed to develop a hypermetabolic response. One day prior to evaluation, all animals were fasted to deplete glycogen stores. Four days post-burn, blood flow rates in major vessels of the liver were measured, and blood samples harvested. We combined measurements of metabolite concentrations and flow rates in the major vessels entering and leaving the liver with a steady-state mass balance model to generate a quantitative picture of the metabolic state of liver. The main findings were: (1) Sham-burned animals exhibited a gluconeogenic pattern, consistent with the fasted state; (2) the 20% TBSA burn inhibited gluconeogenesis and exhibited glycolytic-like features with very few other significant changes; (3) the 40% TBSA burn, by contrast, further enhanced gluconeogenesis and also increased amino acid extraction, urea cycle reactions, and several reactions involved in oxidative phosphorylation. These results suggest that increasing the severity of injury does not lead to a simple dose-dependent metabolic response, but rather leads to qualitatively different responses.

  15. Genetics Home Reference: potassium-aggravated myotonia

    Science.gov (United States)

    ... structure and function of sodium channels. The altered channels cannot properly regulate ion flow, increasing the movement of sodium ions into ... area? Other Names for This Condition PAM sodium channel ... and Rare Diseases Information Center (1 link) Potassium aggravated myotonia Additional ...

  16. Alcohol and liver, 2010

    Institute of Scientific and Technical Information of China (English)

    Natalia; A; Osna

    2010-01-01

    Liver is known as an organ that is primarily affected by alcohol. Alcoholic liver disease (ALD) is the cause of an increased morbidity and mortality worldwide. Progression of ALD is driven by "second hits". These second hits include the complex of nutritional, pharmacological, genetic and viral factors, which aggravate liver pathology. However, in addition to liver failure, ethanol causes damage to other organs and systems. These extrahepatic manifestations are regulated via the similar hepatitis mechanisms...

  17. Bone marrow-derived mesenchymal stem cells protect against experimental liver fibrosis in rats

    Institute of Scientific and Technical Information of China (English)

    Dong-Chang Zhao; Jun-Xia Lei; Rui Chen; Wei-Hua Yu; Xiu-Ming Zhang; Shu-Nong Li; Peng Xiang

    2005-01-01

    AIM: Recent reports have shown the capacity of mesenchymal stem cells (MSCs) to differentiate into hepatocytes in vitro and in vivo. MSCs administration could repair injured liver, lung, or heart through reducing inflammation, collagen deposition, and remodeling. These results provide a clue to treatment of liver fibrosis. The aim of this study was to investigate the effect of infusion of bone marrow (BM)-derived MSCs on the experimental liver fibrosis in rats.METHODS: MSCs isolated from BM in male Fischer 344 rats were infused to female Wistar rats induced with carbon tetrachloride (CCl4) or dimethylnitrosamine (DMN).There were two random groups on the 42nd d of CCl4:CCl4/MSCs, to infuse a dose of MSCs alone; CCl4/saline,to infuse the same volume of saline as control. There were another three random groups after exposure to DMN: DMN10/MSCs, to infuse the same dose of MSCs on d 10; DMN10/saline, to infuse the same volume of saline on d 10; DMN20/MSCs, to infuse the same dose of MSCson d 20. The morphological and behavioral changes ofrats were monitored everyday. After 4-6 wk of MSCs administration, all rats were killed and fibrosis index were assessed by histopathology and radioimmunoassay. Smooth muscle alpha-actin (alpha-SMA) of liver were tested by immunohistochemistry and quantified by IBAS 2.5 software. Male rats sex determination region on the Y chromosome (sry) gene were explored by PCR.RESULTS: Compared to controls, infusion of MSCsreduced the mortality rates of incidence in CCl4-induced model (10% vs 20%) and in DMN-induced model (2040% vs 90%).The amount of collagen deposition and alpha-SMA staining was about 40-50% lower in liver of rats with MSCs than that of rats without MSCs. The similar results were observed in fibrosis index. And the effect of the inhibition of fibrogenesis was greater in DMN10/MSCs than in DMN20/MSCs. The sry gene was positive in the liver of rats with MSCs treatment by PCR.CONCLUSION: MSCs treatment can protect against

  18. Detection of Entamoeba histolytica in experimentally induced amoebic liver abscess:comparison of three staining methods

    Institute of Scientific and Technical Information of China (English)

    Tan Zi Ning; Wong Weng Kin; Shaymoli Mustafa; Arefuddin Ahmed; Rahmah Noordin; Tan Gim Cheong; Olivos-Garcia Alfonso; Lim Boon Huat

    2012-01-01

    Objective: To compare the efficacy of three different tissue stains, namely haematoxylin and eosin (H&E), periodic-acid Schiff (PAS) and immunohistochemical (IHC) stains for detection of Entamoeba histolytica (E. histolytica) trophozoites in abscessed liver tissues of hamster.Methods:Amoebic liver abscess was experimentally induced in a hamster by injecting 1 × 106 of axenically cultured virulent E. histolytica trophozoites (HM1-IMSS strain) into the portal vein. After a week post-inoculation, the hamster was sacrificed and the liver tissue sections were stained with H&E, PAS and IHC stains to detect the amoebic trophozoite. Results: The three stains revealed tissue necrosis and amoebic trophozoites, but with varying clarity. H&E and PAS stained the trophozoites pink and magenta, respectively, however it was difficult to differentiate the stained trophozoites from the macrophages because of their similarity in size and morphology. On the other hand, IHC stain revealed distinct brown appearance of the trophozoites in the infected liver tissues. Conclusions: It can be concluded that out of the three stains, IHC is the best for identification of E. histolytica trophozoites in tissue sections.

  19. Experimental models of non-alcoholic fatty liver disease in rats.

    Science.gov (United States)

    Kucera, Otto; Cervinkova, Zuzana

    2014-07-14

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world, and it persists at a high prevalence. NAFLD is characterised by the accumulation of triglycerides in the liver and includes a spectrum of histopathological findings, ranging from simple fatty liver through non-alcoholic steatohepatitis (NASH) to fibrosis and ultimately cirrhosis, which may progress to hepatocellular carcinoma. The pathogenesis of NAFLD is closely related to the metabolic syndrome and insulin resistance. Understanding the pathophysiology and treatment of NAFLD in humans has currently been limited by the lack of satisfactory animal models. The ideal animal model for NAFLD should reflect all aspects of the intricate etiopathogenesis of human NAFLD and the typical histological findings of its different stages. Within the past several years, great emphasis has been placed on the development of an appropriate model for human NASH. This paper reviews the widely used experimental models of NAFLD in rats. We discuss nutritional, genetic and combined models of NAFLD and their pros and cons. The choice of a suitable animal model for this disease while respecting its limitations may help to improve the understanding of its complex pathogenesis and to discover appropriate therapeutic strategies. Considering the legislative, ethical, economical and health factors of NAFLD, animal models are essential tools for the research of this disease.

  20. H-Ras Oncogene Expression and Angiogenesis in Experimental Liver Cirrhosis

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    Gülsüm Özlem Elpek

    2013-01-01

    Full Text Available Background. Proto-oncogenes, particularly ras, may not only affect cell proliferation but also contribute to angiogenesis by influencing both proangiogenic and antiangiogenic mediators. The aim of this study was to investigate whether any relationship exists between ras expression and angiogenesis during diethylnitrosamine- (DEN- induced experimental liver fibrosis. Materials and Methods. Liver cirrhosis was induced in rats by intraperitoneal injections of DEN. The animals were sacrificed 2 weeks after the last administrations and a hepatectomy was performed. Masson’s trichrome staining was used in the evaluation of the extent of liver fibrosis. The vascular density in portal and periportal areas was assessed by determining the count of CD34 labeled vessel sections. For quantitative evaluation of H-ras expression, in each section positive and negative cells were counted. Results. In fibrotic group H-ras expression was higher than that in nonfibrotic group and was more widespread in cirrhotic livers. Friedman’s test showed that there was a significant correlation between H-ras expression and VD (P<0.01. Conclusion. The results of this descriptive study reveal that H-ras expression gradually increases according to the severity of fibrosis and strongly correlates with angiogenesis.

  1. Effect of fasting on the metabolic response of liver to experimental burn injury.

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    Mehmet A Orman

    Full Text Available Liver metabolism is altered after systemic injuries such as burns and trauma. These changes have been elucidated in rat models of experimental burn injury where the liver was isolated and perfused ex vivo. Because these studies were performed in fasted animals to deplete glycogen stores, thus simplifying quantification of gluconeogenesis, these observations reflect the combined impact of fasting and injury on liver metabolism. Herein we asked whether the metabolic response to experimental burn injury is different in fed vs. fasted animals. Rats were subjected to a cutaneous burn covering 20% of the total body surface area, or to similar procedures without administering the burn, hence a sham-burn. Half of the animals in the burn and sham-burn groups were fasted starting on postburn day 3, and the others allowed to continue ad libitum. On postburn day 4, livers were isolated and perfused for 1 hour in physiological medium supplemented with 10% hematocrit red blood cells. The uptake/release rates of major carbon and nitrogen sources, oxygen, and carbon dioxide were measured during the perfusion and the data fed into a mass balance model to estimate intracellular fluxes. The data show that in fed animals, injury increased glucose output mainly from glycogen breakdown and minimally impacted amino acid metabolism. In fasted animals, injury did not increase glucose output but increased urea production and the uptake of several amino acids, namely glutamine, arginine, glycine, and methionine. Furthermore, sham-burn animals responded to fasting by triggering gluconeogenesis from lactate; however, in burned animals the preferred gluconeogenic substrate was amino acids. Taken together, these results suggest that the fed state prevents the burn-induced increase in hepatic amino acid utilization for gluconeogenesis. The role of glycogen stores and means to increase and/or maintain internal sources of glucose to prevent increased hepatic amino acid

  2. Human liver finite element model validation using compressive and tensile experimental data - biomed 2013.

    Science.gov (United States)

    Davis, Matthew L; Moreno, Daniel P; Vavalle, Nicholas A; Gayzik, F Scott

    2013-01-01

    Motor vehicle crashes commonly result in blunt abdominal trauma. Approximately 19,000 such injuries occur each year in the United States. While finite element models of the human body are becoming an important tool for injury assessment, their reliability depends on the accuracy of the material models used. Recently, Samur et al. proposed a hyperelastic and viscoelastic material model of the liver. The aim of this study was to compare the results of a computational model using this material law to uniaxial tension and compression data from biomechanical tests on liver samples by Kemper et al. In this study, the liver samples were modeled using the finite element method. Both the tension and compression test specimen geometries were created from descriptions in the literature. Each sample was meshed using four approaches: fine hexahedral, coarse hexahedral, fine tetrahedral, and coarse tetrahedral. The average element edge lengths of the coarse and fine meshes were 5 mm and 2.5 mm respectively. The samples were loaded in both tension and compression at four rates: 0.01 strain/sec, 0.1 strain/sec, 1 strain/sec, and 10 strain/sec. For each mesh type (n=4), strain rate (n=4), and loading condition (n=2), 32 simulations in total, the results were plotted against the published experimental data. The results were quantitatively evaluated for magnitude and phase agreement with the experimental data using an objective comparison software package, CORA. The model predicted the tensile response of the liver sample more accurately than the compressive response with an average CORA size error factor of 0.66 versus 0.19 for the compressive model (1 is a perfect match). The fine tetrahedral, fine hexahedral, and coarse hexahedral meshes predicted a similar response. The worst performing mesh was the coarse tetrahedral mesh, which had an average size error factor of 8.6% higher than the fine tetrahedral simulations. The peak stress in both tension and compression varied as a

  3. An implantable rat liver tumor model for experimental transarterial chemoembolization therapy and its imaging features

    Institute of Scientific and Technical Information of China (English)

    Xin Li; Chuan-Sheng Zheng; Gan-Sheng Feng; Chen-Kai Zhuo; Jun-Gong Zhao; Xi Liu

    2002-01-01

    AIM: To establish an ideal implantable rat liver tumor model for interventional therapy study and examine its angiographic signs and MRI, CT features before and after embolization. METHODS: Forty male Wistar rats were implanted with Walker256 tumor in the left lateral lobe of liver. Digital subtraction angiography (DSA) and transarterial chemoembolization were performed on day 14 after implantation. Native computer tomography (CT, n=8) and native magnetic resonance (MR,n=40) were performed between the day 8 and day 21 after implantation. The radiological morphological characteristics were correlated with histological findings.RESULTS: Successful implantation was achieved in all forty rats, which was confirmed by CT and MRI. MR allowed tumor visualization from day 8 while CT from day 11 after implantation. The tumors were hypodensity on CT, hypointense on MR T1-weighted and hyperintense on T2-weighted. The model closely resembled human hepatocardnoma in growth pattem and the lesions were rich in vasculature on angiography and got its filling mainly from the hepatic artery. Before therapy, tumor size was 211.9±48.7 mm3. No ascites, satellite liver nodules or lung metastasis were found. One week after therapy, tumor size was 963.6±214.8 mm3 in the control group and 356.5±78.4mm3 in TACE group. Ascites (4/40), satellite liver nodules (7/40) or lung metastasis (3/40) could be seen on day 21.CONCLUSION: Walker-256 tumor rat model is suitable for the interventional experiment. CT and MRI are helpful in animal optioning and evaluating experimental results.

  4. Recombinant human acid sphingomyelinase as an adjuvant to sorafenib treatment of experimental liver cancer.

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    Radoslav Savić

    Full Text Available BACKGROUND: Hepatocellular carcinoma (HCC is the most common form of liver cancer and the third leading cause of cancer death worldwide. The only approved systemic treatment for unresectable HCC is the oral kinase inhibitor, sorafenib. Recombinant human acid sphingomyelinase (rhASM, which hydrolyzes sphingomyelin to ceramide, is an orphan drug under development for the treatment of Type B Niemann-Pick disease (NPD. Due to the hepatotropic nature of rhASM and its ability to generate pro-apoptotic ceramide, this study evaluated the use of rhASM as an adjuvant treatment with sorafenib in experimental models of HCC. METHODOLOGY/PRINCIPAL FINDINGS: In vitro, rhASM/sorafenib treatment reduced the viability of Huh7 liver cancer cells more than sorafenib. In vivo, using a subcutaneous Huh7 tumor model, mouse survival was increased and proliferation in the tumors decreased to a similar extent in both sorafenib and rhASM/sorafenib treatment groups. However, combined rhASM/sorafenib treatment significantly lowered tumor volume, increased tumor necrosis, and decreased tumor blood vessel density compared to sorafenib. These results were obtained despite poor delivery of rhASM to the tumors. A second (orthotopic model of Huh7 tumors also was established, but modest ASM activity was similarly detected in these tumors compared to healthy mouse livers. Importantly, no chronic liver toxicity or weight loss was observed from rhASM therapy in either model. CONCLUSIONS/SIGNIFICANCE: The rhASM/sorafenib combination exhibited a synergistic effect on reducing the tumor volume and blood vessel density in Huh7 xenografts, despite modest activity of rhASM in these tumors. No significant increases in survival were observed from the rhASM/sorafenib treatment. The poor delivery of rhASM to Huh7 tumors may be due, at least in part, to low expression of mannose receptors. The safety and efficacy of this approach, together with the novel findings regarding enzyme targeting

  5. Circulating extracellular vesicles with specific proteome and liver microRNAs are potential biomarkers for liver injury in experimental fatty liver disease.

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    Davide Povero

    Full Text Available BACKGROUND & AIM: Nonalcoholic fatty liver disease (NAFLD is the most common chronic liver disease in both adult and children. Currently there are no reliable methods to determine disease severity, monitor disease progression, or efficacy of therapy, other than an invasive liver biopsy. DESIGN: Choline Deficient L-Amino Acid (CDAA and high fat diets were used as physiologically relevant mouse models of NAFLD. Circulating extracellular vesicles were isolated, fully characterized by proteomics and molecular analyses and compared to control groups. Liver-related microRNAs were isolated from purified extracellular vesicles and liver specimens. RESULTS: We observed statistically significant differences in the level of extracellular vesicles (EVs in liver and blood between two control groups and NAFLD animals. Time-course studies showed that EV levels increase early during disease development and reflect changes in liver histolopathology. EV levels correlated with hepatocyte cell death (r2 = 0.64, p<0.05, fibrosis (r2 = 0.66, p<0.05 and pathological angiogenesis (r2 = 0.71, p<0.05. Extensive characterization of blood EVs identified both microparticles (MPs and exosomes (EXO present in blood of NAFLD animals. Proteomic analysis of blood EVs detected various differentially expressed proteins in NAFLD versus control animals. Moreover, unsupervised hierarchical clustering identified a signature that allowed for discrimination between NAFLD and controls. Finally, the liver appears to be an important source of circulating EVs in NAFLD animals as evidenced by the enrichment in blood with miR-122 and 192--two microRNAs previously described in chronic liver diseases, coupled with a corresponding decrease in expression of these microRNAs in the liver. CONCLUSIONS: These findings suggest a potential for using specific circulating EVs as sensitive and specific biomarkers for the noninvasive diagnosis and monitoring of NAFLD.

  6. Experimental infection of liver flukes, Fasciola hepatica and Fascioloides magna, in Bison (Bison bison).

    Science.gov (United States)

    Foreyt, William J; Drew, M L

    2010-01-01

    This experimental study was conducted to evaluate the susceptibility of American bison (Bison bison) to liver flukes, Fascioloides magna and Fasciola hepatica. Six bison were each experimentally inoculated with 600 metacercariae of Fascioloides magna, and three were later treated with triclabendazole suspension at 40 mg/kg of body weight. Four additional bison were each experimentally inoculated with 600 metacercariae of Fasciola hepatica. Five control bison were placebo controls. Two controls and all inoculated bison were euthanized 10 mo (Fascioloides magna) and 7 mo (Fasciola hepatica) after inoculation. None of the control bison or the bison inoculated with Fascioloides magna had flukes or lesions characteristic of fluke infection at necropsy. All four bison inoculated with Fasciola hepatica had characteristic liver fluke lesions at necropsy, and three of four bison contained four, 103, and 111 adult flukes, respectively. Fluke eggs were detected in feces of all Fasciola hepatica-inoculated bison during the experiment, but not from the Fascioloides magna-infected bison or control bison. Clinical signs of infection were not observed during the experiment, but hemoglobin and packed cell volumes were lower in the Fasciola hepatica bison when compared to controls, and eosinophil levels were increased. Triclabendazole at 40 mg/kg of body weight appeared to be safe in bison because no toxic reactions were observed. Results from this study indicated bison are susceptible to infection with Fasciola hepatica and are efficient definitive hosts. Because no Fascioloides magna were recovered, bison may have a decreased susceptibility or innate resistance to Fascioloides magna infection, which may account for a lack of reported infections in this host.

  7. Hemostatic disorders in orthotopic and auxiliary liver transplantation : clinical and experimental studies

    NARCIS (Netherlands)

    R.J. Porte (Robert)

    1989-01-01

    textabstractIn patients with severe liver disease, hepatic dysfunction may deteriorate to such an extent that conservative medical treatments are no longer sufficient to maintain the, for life essential, liver functions. For these patients the transplantation of a donor liver represents the only hop

  8. Experimental amoebic liver abscess in hamsters caused by trophozoites of a Brazilian strain of Entamoeba dispar.

    Science.gov (United States)

    Guzmán-Silva, Maria Angélica; Santos, Helena Lúcia Carneiro; Peralta, Regina Saramago; Peralta, José Mauro; de Macedo, Heloisa Werneck

    2013-05-01

    It has been claimed that amoebic molecules such as amoebapore, galactose/N-acetyl galactosamine inhibitable lectin, and cysteine proteases are responsible for host tissue destruction and are present in both pathogenic Entamoeba histolytica and non-pathogenic Entamoeba dispar. Some reports have provided evidence that after infection with E. dispar, pathological changes may occur in some humans. The aim of this study was to evaluate E. dispar pathogenicity by comparing it to the pathogenicity of E. histolytica through liver abscesses induced in hamsters. Syrian golden hamsters were challenged by intrahepatic inoculation with the 03C E. dispar strain or with two strains of E. histolytica (HM1:IMSS and EGG) to compare their virulence grades. As control groups, we used bacterial flora and Pavlova's modified medium. Lesions were verified at 1, 3 and 6 days after inoculation. Multiplex Polymerase Chain Reaction was performed to characterize each strain using EdP1/EdP2 and EhP1/EhP2 primers. The EGG and HM1:IMSS E. histolytica strains and 03C E. dispar were able to cause liver lesions. The EGG strain caused extensive hepatic abscesses, and trophozoites were found in the lesions throughout the three periods of study. The HM1:IMSS strain caused smaller abscesses when compared to EGG lesions; however, trophozoites were observed at 1 and 3 days after inoculation. The 03C E. dispar strain caused intermediate abscesses when compared to the others; trophozoites were observed in all periods analyzed. The EGG strain caused progressive evolution of the injury, which differed from the HM1:IMSS and 03C strains. These results strongly suggest that the 03C E. dispar strain is pathogenic in the experimental hamster model. Additional studies are necessary to identify potential factors that regulate the manifestation of virulence of this strain and others.

  9. Pregnancy aggravates proteinuria in subclinical glomerulonephritis in the rat

    NARCIS (Netherlands)

    Faas, MM; Bakker, WW; Poelman, RT; Schuiling, GA

    1999-01-01

    Because subclinical renal disease may be aggravated during pregnancy-as reflected in the occurrence of proteinuria, for example-we investigated whether a subclinical glomerulonephritis (SG) in the non-pregnant rat (passive Heymann nephritis), a condition without proteinuria, is aggravated when the a

  10. The effect of resveratrol on experimental non-alcoholic fatty liver disease depends on severity of pathology and timing of treatment

    DEFF Research Database (Denmark)

    Heebøll, Sara; El-Houri, Rime Bahij; Hellberg, Ylva Erika Kristina

    2016-01-01

    BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease with few therapeutic options. RSV prevents the development of steatosis in a number of experimental fatty liver (NAFL) models but the preventive or therapeutic effects on experimental NASH...

  11. HEPATOPROTECTIVE ACTION OF POLAR LIPIDS OF MARAL ANTLERS AND PEAT IN EXPERIMENTAL LIVER DAMAGE CAUSED BY ISONIAZIDE AND PARACETAMOL

    Directory of Open Access Journals (Sweden)

    A. I. Yatsenkov

    2013-01-01

    Full Text Available In experimental liver pathology caused by isoniazide or paracetamol administration to albino rats lipids derived from maral antlers and peat decreased the blood activity of aminotransferases, γ-glutamyltranspeptidase, acid and alkaline phosphatases, phospholipase А, content of common bilirubin, activated the detoxication of biliribin, ammonium and phenols, inhibited the liver formation of dienic conjugates, Schiff’s bases, malonic dialdehyde, improve the reduced glutathione function. Maral anthlers and peat lipids in effective doses 30 and 60 mg/kg had the more pronounced hepatoprotective and antioxidant action than lipids in dose 10 mg/kg and essentiale forte N.

  12. Role of Chymase in the Development of Liver Cirrhosis and Its Complications: Experimental and Human Data

    Science.gov (United States)

    Sansoè, Giovanni; Aragno, Manuela; Mastrocola, Raffaella; Mengozzi, Giulio; Novo, Erica; Parola, Maurizio

    2016-01-01

    Background Tissue Angiotensin II (Ang-II), produced through local non ACE-dependent pathways, stimulates liver fibrogenesis, renal vasoconstriction and sodium retention. Aim To highlight chymase-dependent pathway of Ang-II production in liver and kidney during cirrhosis development. Methods Liver histology, portal pressure, liver and kidney function, and hormonal status were investigated in rat liver cirrhosis induced through 13 weeks of CCl4, with or without chymase inhibitor SF2809E, administered between 4th and 13th CCl4 weeks; liver and kidney chymase immunolocation and Ang-II content were assessed. Chymase immunohistochemistry was also assessed in normal and cirrhotic human liver, and chymase mRNA transcripts were measured in human HepG2 cells and activated hepatic stellate cells (HSC/MFs) in vitro. Results Rats receiving both CCl4 and SF2809E showed liver fibrotic septa focally linking portal tracts but no cirrhosis, as compared to ascitic cirrhotic rats receiving CCl4. SF2809E reduced portal pressure, plasma bilirubin, tissue content of Ang-II, plasma renin activity, norepinephrine and vasopressin, and increased glomerular filtration rate, water clearance, urinary sodium excretion. Chymase tissue content was increased and detected in α-SMA-positive liver myofibroblasts and in kidney tubular cells of cirrhotic rats. In human cirrhosis, chymase was located in hepatocytes of regenerative nodules. Human HepG2 cells and HSC/MFs responded to TGF-β1 by up-regulating chymase mRNA transcription. Conclusions Chymase, through synthesis of Ang-II and other mediators, plays a role in the derangement of liver and kidney function in chronic liver diseases. In human cirrhosis, chymase is well-represented and apt to become a future target of pharmacological treatment. PMID:27637026

  13. [Effect of Arnica montana tincture on some hydrolytic enzyme activities of rat liver in experimental toxic hepatitis].

    Science.gov (United States)

    Iaremiĭ, I M; Meshchyshen, I F; Hrihor'ieva, N P; Kostiuk, L S

    1998-01-01

    Effects of tinctura arnica on arginase, adenosine triphosphatase, glucose-6-phosphatase and 5'-nucleotidase activities of rats liver in case of experimental toxic hepatitis have been studied. Toxic hepatitis was caused by 2 times interstomach administration of 0.25 ml oil solution of carbon tetrachloride per 100 g of animal weight. 20 mkl/100 g of tinctura arnica was administered every day per os for 14 days. The enzyme activities have been investigated at 3, 7 and 17 days. A significant demention of a studied hydrolytic enzyme activities in rats liver at intoxication of the body by CCI4 has been shown. It has been established that tinctura arnica administered per os to intoxicated animals sped up the normalization of hydrolytic enzyme activities in rat liver.

  14. Statins activate the canonical hedgehog-signaling and aggravate non-cirrhotic portal hypertension, but inhibit the non-canonical hedgehog signaling and cirrhotic portal hypertension.

    Science.gov (United States)

    Uschner, Frank E; Ranabhat, Ganesh; Choi, Steve S; Granzow, Michaela; Klein, Sabine; Schierwagen, Robert; Raskopf, Esther; Gautsch, Sebastian; van der Ven, Peter F M; Fürst, Dieter O; Strassburg, Christian P; Sauerbruch, Tilman; Diehl, Anna Mae; Trebicka, Jonel

    2015-09-28

    Liver cirrhosis but also portal vein obstruction cause portal hypertension (PHT) and angiogenesis. This study investigated the differences of angiogenesis in cirrhotic and non-cirrhotic PHT with special emphasis on the canonical (Shh/Gli) and non-canonical (Shh/RhoA) hedgehog pathway. Cirrhotic (bile duct ligation/BDL; CCl4 intoxication) and non-cirrhotic (partial portal vein ligation/PPVL) rats received either atorvastatin (15 mg/kg; 7d) or control chow before sacrifice. Invasive hemodynamic measurement and Matrigel implantation assessed angiogenesis in vivo. Angiogenesis in vitro was analysed using migration and tube formation assay. In liver and vessel samples from animals and humans, transcript expression was analyzed using RT-PCR and protein expression using Western blot. Atorvastatin decreased portal pressure, shunt flow and angiogenesis in cirrhosis, whereas atorvastatin increased these parameters in PPVL rats. Non-canonical Hh was upregulated in experimental and human liver cirrhosis and was blunted by atorvastatin. Moreover, atorvastatin blocked the non-canonical Hh-pathway RhoA dependently in activated hepatic steallate cells (HSCs). Interestingly, hepatic and extrahepatic Hh-pathway was enhanced in PPVL rats, which resulted in increased angiogenesis. In summary, statins caused contrary effects in cirrhotic and non-cirrhotic portal hypertension. Atorvastatin inhibited the non-canonical Hh-pathway and angiogenesis in cirrhosis. In portal vein obstruction, statins enhanced the canonical Hh-pathway and aggravated PHT and angiogenesis.

  15. Hepatoprotective effect ofSolanum xanthocarpum fruit extract against CCl4 induced acute liver toxicity in experimental animals

    Institute of Scientific and Technical Information of China (English)

    Ramesh K Gupta; Talib Hussain; G Panigrahi; Avik Das; Gireesh Narayan Singh; K Sweety; Md Faiyazuddin; Chandana Venkateswara Rao

    2011-01-01

    Objective:To investigate the hepatoprotective potential ofSolanum xanthocarpum (Solanaceae) (S. xanthocarpum) in experimental rats to validate its traditional claim.Methods: 50%ethanolic fruit extract ofS. xanthocarpum (SXE, 100, 200or400 mg/kg body weight) was administered daily for14days in experimental animals. Liver injury was induced chemically, byCCl4administration (1 mL/kg i.p.).The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase(ALT), Serum alkaline phosphatise (SALP) and total bilirubin. Meanwhile, in vivo antioxidant activities as lipid peroxidation (LPO), reduced glutathione(GSH), superoxide dismutase(SOD) and catalase(CAT) were screened along with histopathological studies.Results: Obtained results demonstrated that the treatment with SXE significantly (P<0.05- <0.001) and dose-dependently prevented chemically induced increase in serum levels of hepatic enzymes. Furthermore,SXE significantly (up toP<0.001) reduced the lipid peroxidation in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and catalase towards normal levels. Histopathology of the liver tissue showed thatSXE attenuated the hepatocellular necrosis and led to reduction of inflammatory cells inflltration. Conclusions: The results of this study strongly indicate the protective effect ofSXE against acute liver injury which may be attributed to its hepatoprotective activity, and there by scientifically support its traditional use.

  16. Liver regeneration with l-glutamine supplemented diet: experimental study in rats

    Directory of Open Access Journals (Sweden)

    Cibelle Ribeiro Magalhães

    2014-04-01

    Full Text Available OBJECTIVE: To assess liver regeneration in rats after 60% hepatectomy with and without supplementation of L-glutamine through liver weight changes, laboratory parameters and histological study. METHODS: 36 male rats were divided into two groups: glutamine group and control group. Each group was subdivided into three subgroups, with death in 24h, 72h and seven days. The glutamine group received water and standard diet supplemented with L-glutamine, and the control recieved 0.9% saline. In all subgroups analysis of liver regeneration was made by the Kwon formula, study of liver function (AST, ALT, GGT, total bilirubin, indirect and indirect bilirubin and albumin and analysis of cell mitosis by hematoxylin-eosin. RESULTS: In both groups there was liver regeneration by weight gain. Gamma-GT increased significantly in the control group (p < 0.05; albumin increased in the glutamine group. The other indicators of liver function showed no significant differences. Histological analysis at 72h showed a higher number of mitoses in the glutamine group, with no differences in other subgroups. CONCLUSION: Diet supplementation with L glutamine is beneficial for liver regeneration.

  17. Pentoxifylline and melatonin in combination with pioglitazone ameliorate experimental non-alcoholic fatty liver disease.

    Science.gov (United States)

    Zaitone, Sawsan; Hassan, Neven; El-Orabi, Naglaa; El-Awady, El-Sayed

    2011-07-15

    Insulin resistance, oxidative stress and cytokine imbalance are key pathophysiological mechanisms in non-alcoholic fatty liver disease (NAFLD). This study aimed at evaluating the effect of treatment with the insulin sensitizer, pioglitazone, the tumor necrosis factor-α inhibitor, pentoxifylline, and the antioxidant, melatonin and their combinations in rats with NAFLD. Rats were fed a high-fat diet (HFD) for eight weeks to induce NAFLD. For an additional eight weeks, rats were fed the HFD along with pioglitazone, pentoxifylline, melatonin alone or in combination. Liver index and insulin resistance index were calculated. Serum liver enzyme activities, total cholesterol, triglycerides and tumor necrosis factor-α (TNF-α) were determined. Tissue triglycerides, malondialdehyde and reduced glutathione were measured and liver injury was evaluated by histopathological examination. HFD induced severe hepatic steatosis, inflammation and fibrosis. In addition, liver index, insulin resistance index, activities of liver enzymes and serum level of total cholesterol, triglycerides and TNF-α were elevated. This was coupled with an increase in tissue triglycerides, malondialdehyde and depletion of reduced glutathione. Pioglitazone, pentoxifylline and melatonin, alone or in combination; reduced the insulin resistance index, activities of liver enzymes, hepatic malondialdehyde and increased hepatic reduced glutathione level. Pentoxifylline led to a decrease in serum TNF-α level, however, pioglitazone and melatonin reduced serum total cholesterol and triglycerides. In conclusion, data in this study indicate that pentoxifylline and melatonin can be used as promising adjuvant therapies to pioglitazone in the clinical management of NAFLD.

  18. Glutathione metabolism and glucose 6-phosphate dehydrogenase activity in experimental liver injury.

    Directory of Open Access Journals (Sweden)

    Watanabe,Akiharu

    1983-12-01

    Full Text Available Increased activities of liver glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49 and 6-phosphogluconate dehydrogenase (6PGD, EC 1.1.1.44 in the pentose phosphate cycle were accompanied with a depletion of reduced glutathione (GSH following an intragastric administration of carbon tetrachloride (CCl4 to rats. Oxidized glutathione (GSSG also decreased remarkably, keeping the GSSG: GSH ratio constant. No significant alteration of glutathione reductase (EC 1.6.4.2., glutathione peroxidase (EC 1.11.1.9 and malic enzyme (EC 1.1.1.40 activities in the supernatant and gamma-glutamyl transpeptidase (gamma-GTP, EC 2.3.2.2 activity in the homogenate of the injured liver were observed. Furthermore, no marked difference in the GSH-synthesizing activity was found between control and CCl4-intoxicated liver. An intraperitoneal injection of GSH produced a significant increase in liver GSH content in control rats but not in CCl4-treated rats; G6PD activity was not affected. Intraperitoneal injections of diethylmaleate resulted in continuously diminished levels of liver GSH without any alteration of liver G6PD activity. In vitro disappearance of GSH added to the liver homogenate from CCl4-treated rats occurred enzymatically and could not be prevented by the addition of a NADPH-generating system. The results suggest that increased G6PD activity in CCl4-injured liver does not play an important role in the maintenance of glutathione in the reduced form and that the decreased GSH content in the injured liver might be caused by enhanced GSH catabolism not due to gamma-GTP.

  19. Entamoeba histolytica calreticulin: an endoplasmic reticulum protein expressed by trophozoites into experimentally induced amoebic liver abscesses.

    Science.gov (United States)

    González, Enrique; de Leon, Maria del Carmen García; Meza, Isaura; Ocadiz-Delgado, Rodolfo; Gariglio, Patricio; Silva-Olivares, Angelica; Galindo-Gómez, Silvia; Shibayama, Mineko; Morán, Patricia; Valadez, Alicia; Limón, Angelica; Rojas, Liliana; Hernández, Eric G; Cerritos, René; Ximenez, Cecilia

    2011-02-01

    Entamoeba histolytica calreticulin (EhCRT) is remarkably immunogenic in humans (90-100% of invasive amoebiasis patients). Nevertheless, the study of calreticulin in this protozoan is still in its early stages. The exact location, biological functions, and its role in pathogenesis are yet to be fully understood. The aim of the present work is to determine the location of EhCRT in virulent trophozoites in vivo and the expression of the Ehcrt gene during the development of experimentally induced amoebic liver abscesses (ALA) in hamsters. Antibodies against recombinant EhCRT were used for the immunolocalization of EhCRT in trophozoites through confocal microscopy; immunohistochemical assays were also performed on tissue sections of ALAs at different times after intrahepatic inoculation. The expression of the Ehcrt gene during the development of ALA was estimated through both in situ RT-PCR and real-time RT-PCR. Confocal assays of virulent trophozoites showed a distribution of EhCRT in the cytoplasmic vesicles of different sizes. Apparently, EhCRT is not exported into the hepatic tissue. Real-time RT-PCR demonstrated an over-expression of the Ehcrt gene at 30 min after trophozoite inoculation, reaching a peak at 1-2 h; thereafter, the expression fell sharply to its original levels. These results demonstrate for the first time in an in vivo model of ALA, the expression of Ehcrt gene in E. histolytica trophozoites and add evidence that support CRT as a resident protein of the ER in E. histolytica species. The in vivo experiments suggest that CRT may play an important role during the early stages of the host-parasite relationship, when the parasite is adapting to a new environment, although the protein seems to be constitutively synthesized. Moreover, trophozoites apparently do not export EhCRT into the hepatic tissue in ALA.

  20. [Keeping dogs indoor aggravates infantile atopic dermatitis].

    Science.gov (United States)

    Endo, K; Hizawa, T; Fukuzumi, T; Kataoka, Y

    1999-12-01

    We had a two-month-old girl with severe dermatitis since birth. Her serum RAST to HD, Df and Dp were 1.06, 0.03 and 0.01 Ua/ml respectively. A Yorkshire terrier were kept at her mother's parents' home where the patient had lived for a month since birth. Her eczema, which became markedly aggravated whenever she visited there, improved after the elimination of the dog. We investigated the relationship between keeping dogs and infantile atopic dermatitis. We studied 368 patients under the age of two years (211 boys and 157 girls). Skin symptoms were graded globally mild, moderate or severe. Total serum IgE and specific antibody titer to dog dander were measured. We asked them whether they kept dogs and specifically, where they kept dogs, outdoor, indoor, in their own house, or in their grandparents' house. 197 patients had no contact with dogs, 90 patients kept dogs outdoor and 81 patients did indoor. The positive rate of RAST (> or = 0.7 Ua/ml) to dog dander was 6.1%, 17.8% and 46.9% respectively in these three groups. There were strong statistical differences between three groups. On the other hand, among the 81 patients who kept indoor, the RAST positive rates were almost same regarding where the dogs were kept, in their own house or their grandparents' house. Interestingly this difference happens only with patients under the age of 3 months. Patients older than 4 months showed no significant differences in the positive RAST rates, whether they kept dogs indoor or outdoor. This suggests the sensitization occurs before the age of 3 months. Speaking of symptoms, patients who kept dogs indoor showed significantly more severe symptoms than patients who had no contact with dogs and patients who kept dogs outdoor. There was no significant difference between the symptoms of patients who had no contact with dogs and those of patients who kept dogs outdoor. This implies the patient's symptom will improve only by moving the dog out of the house.

  1. Ursodeoxycholic acid inhibits hepatic cystogenesis in experimental models of polycystic liver disease

    NARCIS (Netherlands)

    Munoz-Garrido, P.; Marin, J.J.; Perugorria, M.J.; Urribarri, A.D.; Erice, O.; Saez, E.; Uriz, M.; Sarvide, S.; Portu, A.; Concepcion, A.R.; Romero, M.R.; Monte, M.J.; Santos-Laso, A.; Hijona, E.; Jimenez-Aguero, R.; Marzioni, M.; Beuers, U.; Masyuk, T.V.; LaRusso, N.F.; Prieto, J.; Bujanda, L.; Drenth, J.P.H.; Banales, J.M.

    2015-01-01

    BACKGROUND & AIMS: Polycystic liver diseases (PLDs) are genetic disorders characterized by progressive biliary cystogenesis. Current therapies show short-term and/or modest beneficial effects. Cystic cholangiocytes hyperproliferate as a consequence of diminished intracellular calcium levels ([Ca(2+)

  2. Liver manipulation causes hepatocyte injury and precedes systemic inflammation in patients undergoing liver resection.

    NARCIS (Netherlands)

    Poll, M.C. van de; Derikx, J.P.M.; Buurman, W.A.; Peters, W.H.M.; Roelofs, H.M.J.; Wigmore, S.J.; Dejong, C.H.

    2007-01-01

    BACKGROUND: Liver failure following liver surgery is caused by an insufficient functioning remnant cell mass. This can be due to insufficient liver volume and can be aggravated by additional cell death during or after surgery. The aim of this study was to elucidate the causes of hepatocellular injur

  3. Current experimental perspectives on the clinical progression of alcoholic liver disease.

    Science.gov (United States)

    Breitkopf, Katja; Nagy, Laura E; Beier, Juliane I; Mueller, Sebastian; Weng, Honglei; Dooley, Steven

    2009-10-01

    Chronic alcohol abuse is an important cause of morbidity and mortality throughout the world. Liver damage due to chronic alcohol intoxication initially leads to accumulation of lipids within the liver and with ongoing exposure this condition of steatosis may first progress to an inflammatory stage which leads the way for fibrogenesis and finally cirrhosis of the liver. While the earlier stages of the disease are considered reversible, cirrhotic destruction of the liver architecture beyond certain limits causes irreversible damage of the organ and often represents the basis for cancer development. This review will summarize current knowledge about the molecular mechanisms underlying the different stages of alcoholic liver disease (ALD). Recent observations have led to the identification of new molecular mechanisms and mediators of ALD. For example, plasminogen activator inhibitor 1 was shown to play a central role for steatosis, the anti-inflammatory adipokine, adiponectin profoundly regulates liver macrophage function and excessive hepatic deposition of iron is caused by chronic ethanol intoxication and increases the risk of hepatocellular carcinoma development.

  4. Sleep-related hypoxemia aggravates systematic inflammation in emphysematous rats

    Institute of Scientific and Technical Information of China (English)

    FENG Jing; Ambrose An-Po Chiang; WU Qi; CHEN Bao-yuan; CUI Lin-yang; LIANG Dong-chun; ZHANG Ze-li; YAO Wo

    2010-01-01

    mean linear intercept (MLI) and mean alveolar number (MAN) values than SRHCtrl group. MLI values in SRHStand group were the highest (ail P <0.05). O2Sat in SRHStand rats when SRH exposure was (83.45±1.76)%. Histological scores of lung, liver, pancreas and right carotid artery were higher in emphysematous groups than SRHCtrl group, and SRHStand group were the highest (all P <0.05) (SOD and CAT values were lower and MDA values were higher in groups with emphysema than without and in SRHStand group than in ECtrl group (all P <0.05)). MDA values were the highest in SRHStand group (all P <0.05). Total cellular score in BALF and White blood cell (WBC) in whole blood were the highest in SRHStand group (all P <0.05). Lymphocyte ratios were the highest in SRHStand group both in BALF and blood (all P <0.05). Red blood cell (RBC) and hemoglobin in emphysematous groups were higher than that in SRHCtrl group, and SRHStand group were higher than ECtrl group (all P <0.05).Conclusions With a proper novo model of SRHIE with Wistar rats, we have demonstrated SRH may aggravate the degree of emphysematous changes, polycythemia,oxidative stress and systematic inflammation. SRH and emphysema may have a synergistic action in causing systematic damages, and lymphocyte may be playing a central role in this process. Longer duration and more severe extent of SRHIE exposure also seem to result in more serious systematic damages. The mechanisms of all these concerned processes remain to be studied.

  5. Oxidative Stress and Liver Morphology in Experimental Cyclosporine A-Induced Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Agnieszka Korolczuk

    2016-01-01

    Full Text Available Cyclosporine A is an immunosuppressive drug used after organ’s transplantation. The adverse effects on such organs as kidney or liver may limit its use. Oxidative stress is proposed as one of the mechanisms of organs injury. The study was designed to elucidate CsA-induced changes in liver function, morphology, oxidative stress parameters, and mitochondria in rat’s hepatocytes. Male Wistar rats were used: group A (control receiving physiological saline, group B cyclosporine A in a dose of 15 mg/kg/day subcutaneously, and group C the CsA-vehicle (olive oil. On the 28th day rats were anesthetized. The following biochemical changes were observed in CsA-treated animals: increased levels of ALT, AST, and bilirubin in the serum, statistically significant changes in oxidative stress parameters, and lipid peroxidation products in the liver supernatants: MDA+4HAE, GSH, GSSG, caspase 3 activity, and ADP/ATP, NAD+/NADH, and NADP+/NADPH ratios. Microscopy of the liver revealed congestion, sinusoidal dilatation, and focal hepatocytes necrosis with mononuclear cell infiltration. Electron microscope revealed marked mitochondrial damage. Biochemical studies indicated that CsA treatment impairs liver function and triggers oxidative stress and redox imbalance in rats hepatocytes. Changes of oxidative stress markers parallel with mitochondrial damage suggest that these mechanisms play a crucial role in the course of CsA hepatotoxicity.

  6. Experimental model of microcystin accumulation in the liver of Oreochromis niloticus exposed subchronically to a toxic bloom of Microcystis sp.

    Science.gov (United States)

    Deblois, Charles P; Giani, Alessandra; Bird, David F

    2011-05-01

    Although accumulation of the liver toxin microcystin in phytoplanktivorous fish has been demonstrated in captive fish and in natural ecosystems, the relation between microcystin in ingested algae and the pattern of buildup of microcystin in fish is poorly known. In this month-long study performed at a Brazilian fish farm, 45 mature Oreochromis niloticus were fed daily with fresh seston periodically dominated by toxic Microcystis sp. Microcystin was measured daily in the food and every 5 days in liver and muscle samples. Control fish received a diet of seston that was low in toxic cyanobacteria. Initially, in treatment ponds, microcystin available for fish increased from 6.5 to 66.9 ng microcystin fish(-1)day(-1), which was accompanied by an increase from 5.5 to 35.4 ng microcysting liver(-1). Microcystin in muscle was below our detection limit of 4 ng g tissue(-1) for the entire study. In the bloom phase, available microcystin reached its highest concentration (4450 ng MC fish(-1)day(-1)) then decreased to 910 ng microcystin fish(-1)day(-1) on day 31. During this period, microcystin reached its highest concentration of 81.6 ng MC g liver(-1) and stayed high until the end of the experiment. A model based on rapid uptake, saturation, and exponential loss was built with these experimental results, and verified with data from the literature. Our model showed that accumulation was up to 50% of ingestion at low doses, but at intermediate doses, the onset of elimination led to a decline of liver burden. Although the accumulation rate confirms the high contamination potential of microcystin, it was balanced by a high depuration rate and this efficient systemic elimination may explain the tolerance of these fish to toxic blooms in the wild.

  7. Impact of antithrombin Ⅲ on hepatic and intestinal microcirculation in experimental liver cirrhosis and bowel inflammation: An in vivo analysis

    Institute of Scientific and Technical Information of China (English)

    Sasa-Marcel Maksan; Zilfi (U)lger; Martha Maria Gebhard; Jan Schmidt

    2005-01-01

    AIM: To analyze the hepatic and intestinal microcirculation in an animal model of liver cirrhosis and inflammatory bowel disease (IBD) and to characterize the anti-inflammatory action of antithrombin Ⅲ (ATⅢ) on leukocyte kinetics and liver damage.METHODS: Hepatic and intestinal microcirculation was investigated by intravital videomicroscopy. Standardized models of experimental chronic liver cirrhosis and bowel inflammation were employed. Animals were divided into four groups (n = 6/group): controls, animals with cirrhosis,animals with cirrhosis and IBD, animals with cirrhosis and IBD treated with ATⅢ.RESULTS: Cirrhosis facilitated leukocyte rolling and sticking in hepatic sinusoids (1.91±0.28 sticker/μm vs0.5±0.5 sticker/μm in controls, P<0.05). The effect enhanced in animals with cirrhosis and IBD (5.4±1.65sticker/μm), but reversed agter ATⅢ application (3.97±1.04sticker/μm, P<0.05). Mucosal blood flow showed no differences in cirrhotic animals and controls (5.3±0.31nL/min vs5.4±0.25 nL/min) and was attenuated in animals with cirrhosis and IBD significantly (3.49±0.6 nL/min). This effect was normalized in the treatment group (5.13±0.4nL/min, P<0.05). Enzyme values rose during development of cirrhosis and bowel inflammation, and reduced after ATⅢ application (P<0.05).CONCLUSION: Liver cirrhosis in the presence of IBD leads to a significant reduction in mucosal blood flow and an increase in hepatic leukocyte adherence with consecutive liver injury, which can be prevented by administration of ATⅢ.

  8. Boron Neutron Capture Therapy (BCNT) for the Treatment of Liver Metastases: Biodistribution Studies of Boron Compounds in an Experimental Model

    Energy Technology Data Exchange (ETDEWEB)

    Marcela A. Garabalino; Andrea Monti Hughes; Ana J. Molinari; Elisa M. Heber; Emiliano C. C. Pozzi; Maria E. Itoiz; Veronica A. Trivillin; Amanda E. Schwint; Jorge E. Cardoso; Lucas L. Colombo; Susana Nievas; David W. Nigg; Romina F. Aromando

    2011-03-01

    Abstract We previously demonstrated the therapeutic efficacy of different boron neutron capture therapy (BNCT) protocols in an experimental model of oral cancer. BNCT is based on the selective accumulation of 10B carriers in a tumor followed by neutron irradiation. Within the context of exploring the potential therapeutic efficacy of BNCT for the treatment of liver metastases, the aim of the present study was to perform boron biodistribution studies in an experimental model of liver metastases in rats. Different boron compounds and administration conditions were assayed to determine which administration protocols would potentially be therapeutically useful in in vivo BNCT studies at the RA-3 nuclear reactor. A total of 70 BDIX rats were inoculated in the liver with syngeneic colon cancer cells DHD/K12/TRb to induce the development of subcapsular tumor nodules. Fourteen days post-inoculation, the animals were used for biodistribution studies. We evaluated a total of 11 administration protocols for the boron compounds boronophenylalanine (BPA) and GB-10 (Na210B10H10), alone or combined at different dose levels and employing different administration routes. Tumor, normal tissue, and blood samples were processed for boron measurement by atomic emission spectroscopy. Six protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue. Boron concentration values in tumor and normal tissues in the liver metastases model show it would be feasible to reach therapeutic BNCT doses in tumor without exceeding radiotolerance in normal tissue at the thermal neutron facility at RA-3.

  9. The Relationship between Portal Venous and Hepatic Arterial Blood Flow. I. Experimental Liver Transplantation

    Directory of Open Access Journals (Sweden)

    F. Jakab

    1996-01-01

    Full Text Available The relationship between the changes in portal venous and hepatic arterial blood flows, in the liver is a much disputed question, it has tremendous significance in the practice of transplantation, and an explanation has been available since 1981, when Lautt published the so-caled “adenosine washout theory”. According to our earlier observations the decrease of portal pressure or flow consistently led to an increase in hepatic artery flow. At the same time changes in hepatic artery flow or pressure seemed to produce only inconsistent effects on the portal circulation. In the present experiments liver transplantation (OLTX was carried out on mongrel dogs by Starzl's method. Electromagnetic flow probes were placed on the hepatic artery and the portal vein before removal of recipient’s liver, and after completion of all vascular anastomoses to the newly inserted liver, during the recirculatory phase of OLTX. The flow probes were connected to a Hellige electromagnetic flowmeter, portal venous and systemic arterial pressures were also recorded.

  10. Peroxynitrite and Peroxiredoxin in the Pathogenesis of Experimental Amebic Liver Abscess

    Directory of Open Access Journals (Sweden)

    Judith Pacheco-Yepez

    2014-01-01

    Full Text Available The molecular mechanisms by which Entamoeba histolytica causes amebic liver abscess (ALA are still not fully understood. Amebic mechanisms of adherence and cytotoxic activity are pivotal for amebic survival but apparently do not directly cause liver abscess. Abundant evidence indicates that chronic inflammation (resulting from an inadequate immune response is probably the main cause of ALA. Reports referring to inflammatory mechanisms of liver damage mention a repertoire of toxic molecules by the immune response (especially nitric oxide and reactive oxygen intermediates and cytotoxic substances released by neutrophils and macrophages after being lysed by amoebas (e.g., defensins, complement, and proteases. Nevertheless, recent evidence downplays these mechanisms in abscess formation and emphasizes the importance of peroxynitrite (ONOO−. It seems that the defense mechanism of amoebas against ONOO−, namely, the amebic thioredoxin system (including peroxiredoxin, is superior to that of mammals. The aim of the present text is to define the importance of ONOO− as the main agent of liver abscess formation during amebic invasion, and to explain the superior capacity of amoebas to defend themselves against this toxic agent through the peroxiredoxin and thioredoxin system.

  11. Evidence of oxidative stress in brain and liver of young rats submitted to experimental galactosemia.

    Science.gov (United States)

    Castro, Márcia B; Ferreira, Bruna K; Cararo, José Henrique; Chipindo, Adália E; Magenis, Marina L; Michels, Monique; Danielski, Lucinéia G; de Oliveira, Marcos R; Ferreira, Gustavo C; Streck, Emilio L; Petronilho, Fabricia; Schuck, Patrícia F

    2016-12-01

    Galactosemia is a disorder of galactose metabolism, leading to the accumulation of this carbohydrate. Galactosemic patients present brain and liver damage. For evaluated oxidative stress, 30-day-old males Wistar rats were divided into two groups: galactose group, that received a single injection of this carbohydrate (5 μmol/g), and control group, that received saline 0.9 % in the same conditions. One, twelve or twenty-four hours after the administration, animals were euthanized and cerebral cortex, cerebellum, and liver were isolated. After one hour, it was found a significant increase in TBA-RS levels, nitrate and nitrite and protein carbonyl contents in cerebral cortex, as well as protein carbonyl content in the cerebellum and in hepatic level of TBA-RS, and a significant decrease in nitrate and nitrite contents in cerebellum. TBA-RS levels were also found increased in all studied tissues, as well as nitrate and nitrite contents in cerebral cortex and cerebellum, that also present increased protein carbonyl content and impairments in the activity of antioxidant enzymes of rats euthanized at twelve hours. Finally, animals euthanized after twenty-four hours present an increase of TBA-RS levels in studied tissues, as well as the protein carbonyl content in cerebellum and liver. These animals also present an increased nitrate and nitrite content and impairment of antioxidant enzymes activities. Taken together, our data suggest that acute galactose administration impairs redox homeostasis in brain and liver of rats.

  12. Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals

    Directory of Open Access Journals (Sweden)

    Izzettin Fikret V

    2008-07-01

    Full Text Available Abstract Background The first line anti-tuberculosis drugs isoniazid (INH, rifampicin (RIF and pyrazinamide (PZA continues to be the effective drugs in the treatment of tuberculosis, however, the use of these drugs is associated with toxic reactions in tissues, particularly in the liver, leading to hepatitis. Silymarin, a standard plant extract with strong antioxidant activity obtained from S. marianum, is known to be an effective agent for liver protection and liver regeneration. The aim of this study was to investigate the protective actions of silymarin against hepatotoxicity caused by different combinations of anti-tuberculosis drugs. Methods Male Wistar albino rats weighing 250–300 g were used to form 6 study groups, each group consisting of 10 rats. Animals were treated with intra-peritoneal injection of isoniazid (50 mg/kg and rifampicin (100 mg/kg; and intra-gastric administration of pyrazinamid (350 mg/kg and silymarin (200 mg/kg. Hepatotoxicity was induced by a combination of drugs with INH+RIF and INH+RIF+PZA. Hepatoprotective effect of silymarin was investigated by co-administration of silymarin together with the drugs. Serum biochemical tests for liver functions and histopathological examination of livers were carried out to demonstrate the protection of liver against anti-tuberculosis drugs by silymarin. Results Treatment of rats with INH+RIF or INH+RIF+PZA induced hepatotoxicity as evidenced by biochemical measurements: serum alanine aminotransferase (ALT, aspartate aminotransferase (AST and alkaline phosphatase (ALP activities and the levels of total bilirubin were elevated, and the levels of albumin and total protein were decreased in drugs-treated animals. Histopathological changes were also observed in livers of animals that received drugs. Simultaneous administration of silymarin significantly decreased the biochemical and histological changes induced by the drugs. Conclusion The active components of silymarin had

  13. Porcine liver: experimental model for the intra-hepatic glissonian approach Figado suíno: modelo experimental para o acesso glissoniano intra-hepático

    Directory of Open Access Journals (Sweden)

    Antonio Cavalcanti de Albuquerque Martins

    2008-04-01

    Full Text Available PURPOSE: The aim of the study is to evaluate the porcine liver as a teaching and training model for the glissonian approach. METHODS: Ten livers were removed from domestic adult white pigs weighting 35 to 45kg. Based on anatomical landmarks, the glissonian pedicles of each liver segments were dissected and biopsies were taken for histological examination, to analyze the presence of the glissonian sheath. RESULTS: During microscopic examination, a sheath of conjunctive tissue was observed wrapping each segmental pedicle in porcine liver. This could be clearly seen when histological preparation for connective tissue was obtained (Masson technique. CONCLUSION: The morphological arrangement of glissonian pedicles in porcine liver makes this model a useful tool for training the intra-hepatic glissonian approach.OBJETIVO: Avaliar a utilização do fígado suíno como um modelo experimental para o ensino e treinamento da técnica glissoniana intra-hepática nas ressecções do fígado. MÉTODOS: Foram utilizados 10 fígados inteiros de porcos adultos brancos, pesando entre 35-45 kg. Os pedículos glissonianos de vários segmentos foram dissecados e ressecados para a realização de estudos histológicos e verificação da presença da bainha conjuntiva ao longo das tríades portais. RESULTADOS: Na microscopia, uma bainha de tecido conjuntivo foi encontrada envolvendo os pedículos glissonianos no fígado suíno. A utilização de preparações específicas para o tecido conjuntivo (Masson ressaltou a presença dessa bainha em cada pedículo. CONCLUSÃO: As características morfológicas dos pedículos glissonianos suínos, fazem desse modelo experimental um método de treinamento da técnica glissoniana intra-hepática.

  14. [Aggravation after Diagnosis of Sudden Sensorineural Hearing Loss].

    Science.gov (United States)

    Fukumoto, Ichiro; Nemoto, Toshimitsu; Tsukuda, Tomoko; Koshizuka, Keiichi

    2015-03-01

    Among 95 patients with sudden sensorineural hearing loss who received inpatient treatment at our hospital within the 27-month period between October 2009 and December 2011, those in whom hearing loss was aggravated after diagnosis were compared with a control group. Hearing loss aggravation was defined as a decrease by 10 dB or more in the mean hearing threshold at 5 frequencies from 250 to 4,000 Hz or decrease of 15 dB or more in the hearing threshold at 2 consecutive frequencies. Hearing loss was aggravated after diagnosis in 22 (23.2%) of the 95 patients, showing a similar tendency to that previously reported. Although the grades of hearing loss in these patients were higher than those in 73 control group patients, according to the sudden hearing loss severity classification, their outcomes were favorable. The hearing loss aggravation group consisted of those with steroid-dependent hearing loss (6) and those who had undergone perilymphatic fistula repair (4), in addition to a large number of patients with idiopathic hearing loss, including suspicious perilymphatic fistula (10). When hearing loss becomes aggravated after the diagnosis of sudden sensorineural hearing loss, it may be important to determine the most appropriate approach in each case, such as a careful and gradual decrease in the adenocortical steroid dose and the consideration of perilymphatic fistula repair.

  15. Experimental Study of the Prophylactic and Therapeutic Effects of Venin on Metastasis and Recurrence of Liver Cancer

    Institute of Scientific and Technical Information of China (English)

    JingjingSun; ZhiyongWu; XindaZhou; YinkunLiu

    2004-01-01

    OBJECTIVE To study the inhibitory effect of venin on adhesion and invasive ability of SMMC-7721 cells and to examine the prophylactic and therapeutic effect of venin on liver cancer metastasis and recurrence after hepatectomy.METHODS The blocking effect of venin on the intercellular adhesive molecule (ICAM-1) of 7721 cells was analyzed by immunofluorescence flow cytometry. The influence of venin on the invasive ability of 7721 cells was observed by cell-migration experimentation and detachment of 7721 cells attached to fibronectin (FN), and the influence of venin on adhesion of 7721 cells to FN by the MTT method, 7721 cells to 7721 cells, 7721 cells to lymphocytes, and 7721 cells to endothelial cells by a cellular adhesion test. The preventive and therapeutic effect of venin onmetastasis and recurrence of a liver cancer model was observed in nudemice after hepatectomy. RESULTS The expression of ICAM-1 in the venin-treated group was significantly lower than that in the untreated group. Venin could not inhibit the invasive ability of 7721 cells, and could not exfoliate the 7721 cells adhered to FN. It could inhibit the adhesion between 7721 cells and 7721 cells, and between 7721 and endothelial cells, but could not inhibit the adhesion between 7721 and lymphocytes. The nude mice treated with venin had less intrahepatic or extrahepatic metastases and recurrences after hepatectomy. CONCLUSION Venin can inhibit the adhesive ability of SMMC-7721 cells and can also prevent and treat the metastasis and recurrence of liver cancer in nude mice after hepatectomy.

  16. Ultrastructural and biochemical aspects of liver mitochondria during recovery from ethanol-induced alterations. Experimental evidence of mitochondrial division.

    Science.gov (United States)

    Koch, O. R.; Roatta de Conti, L. L.; Bolaños, L. P.; Stoppani, A. O.

    1978-01-01

    To study the morphologic and biochemical changes occuring in liver mitochondria during recovery from ethanol-induced injury, rats fed a 6-month high-alcohol regimen plus a nutritionally adequate diet which did not induce fatty liver were compared with isocalorically fed controls. After this period the alcohol-fed animals displayed striking ultrastructural changes of liver mitochondria and a decreased respiratory activity with succinate or malate-glutamate as substrate. On the contrary, the respiratory rate with I-glycerophosphate was 50% increased. Regression changes were studied after alcohol was withdrawn from the diet. Enlarged mitochondria rapidly disappeared (in 24 hours), although a few megamitochondria were still present after 8 days of abstinence. A similar recovery was observed for the functional alterations. At the end of the experimental period, only a slight decrease of the maximal respiratory rate using malate-glutamate as a substrate was noted. The ultrastructural findings and the morphometric data suggest that the way in which mitochondrial normalization takes place is based on partition of these organelles. Images Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 1 Figure 2 Figure 13 PMID:623205

  17. Role of monocytes and macrophages in experimental and human acute liver failure

    Institute of Scientific and Technical Information of China (English)

    Lucia; A; Possamai; Charalambos; Gustav; Antoniades; Quentin; M; Anstee; Alberto; Quaglia; Diego; Vergani; Mark; Thursz; Julia; Wendon

    2010-01-01

    Acute liver failure (ALF) is a devastating clinical syndrome characterised by progressive encephalopathy, coagulopathy, and circulatory dysfunction, which commonly leads to multiorgan failure and death. Central to the pathogenesis of ALF is activation of the immune system with mobilisation of cellular effectors and massive production of cytokines. As key components of the innate immune system, monocytes and macrophages are postulated to play a central role in the initiation, progression and resolution of AL...

  18. Aggravation of clozapine-induced hepatotoxicity by glycyrrhetinic acid in rats.

    Science.gov (United States)

    Jia, Ling-ling; Zhong, Ze-yu; Li, Feng; Ling, Zhao-li; Chen, Yang; Zhao, Wei-man; Li, Ying; Jiang, Shu-wen; Xu, Ping; Yang, Yang; Hu, Meng-yue; Liu, Li; Liu, Xiao-dong

    2014-01-01

    Clozapine (CLZ) was reported to be associated with hepatotoxicity. Glycyrrhetinic acid (GA) has a liver protective effect. Our preliminary experiments showed that GA aggravated rather than attenuated CLZ-induced hepatotoxicity in primary cultured rat hepatocytes. The study aimed to describe the enhancing effect of GA on CLZ-induced hepatotoxicity in vivo and in vitro. Data from primary cultured rat hepatocytes showed the decreased formation of metabolites demethylclozapine (nor-CLZ) and clozapine N-oxide (CLZ N-oxide). The results in vivo showed that 7-day CLZ treatment led to marked accumulation of triglyceride (TG) and increase in γ-glutamyl transpeptidase (γ-GT) activity, liver weight, and serum AST in rats. Co-administration of GA enhanced the increases in hepatic TG, γ-GT, liver weight, and serum total cholesterol induced by CLZ. GA decreased plasma concentrations of nor-CLZ and CLZ N-oxide. Compared with control rats, hepatic microsomes of GA rats exhibited the decreased formations of nor-CLZ and CLZ N-oxide, accompanied by decreases in activities of CYP2C11 and CYP2C19 and increased activity of CYP1A2. QT-PCR analysis demonstrated that GA enhanced expression of CYP1A2, but suppressed expression of CYP2C11 and CYP2C13. All these results support the conclusion that GA aggravated CLZ-induced hepatotoxicity, which was partly via inhibiting CYP2C11 and CYP2C13 or inducing CYP1A2.

  19. Protective effect of Mollugo nudicaulis Lam. on acute liver injury induced by perchloroethylene in experimental rats

    Institute of Scientific and Technical Information of China (English)

    Sundaraj Rajamanikandan; Thangaraj Sindhu; Dhanapal Durgapriya; Dominic Sophia; Paramasivam Ragavendran

    2012-01-01

    Objective:To evaluate the protective effect of ethanol extract of Mollugo nudicaulis (M. nudicaulis) against perchloroethylene-induced hepatotoxicity. Methods: The hepatoprotective activity of the ethanol extract of M. nudicaulis (200 mg/kg body wt) was studied in percholoroethylene (1 000 mg/kg body wt) induced hepatotoxicity in Wistar albino rats. The serum levels of AST, ALT, ALP, bilirubin and the liver content of SOD, CAT, GPx, GST, GSH, vitamin C were assessed to evaluate the hepatoprotective and antioxidant activities of the extract. The activity of the extract was compared with silymarin, a standard reference drug. In addition, serum urea, uric acid and creatinine levels were measured to evaluate the kidney function. The histopathological examination of the liver tissues was observed to support the biochemical parameters. Results:The results revealed that the extract significantly (P<0.05) restored the serum levels of AST, ALT, ALP, bilirubin and significantly (P<0.05) increased the antioxidant enzymes SOD, CAT, GPx, GST, GSH, vitamin C in perchloroethylene-induced rats to its normalcy. The biochemical observations were supported by the histopathological studies of the liver tissues. Conclusions:The results led to the conclusion that M. nudicaulis possess hepatoprotective and antioxidant activites against perchloroethylene-induced hepatotoxicity in rats.

  20. Carvacrol attenuates N-nitrosodiethylamine induced liver injury in experimental Wistar rats

    Directory of Open Access Journals (Sweden)

    Balan Rajan

    2015-06-01

    Full Text Available Carvacrol is a main constituent in the essential oils of countless aromatic plants including Origanum Vulgare and Thymus vulgari, which has been assessed for substantial pharmacological properties. In recent years, notable research has been embarked on to establish the biological actions of Carvacrol for its promising use in clinical applications. The present study is an attempt to reveal the protective role of Carvacrol against N-Nitrosodiethylamine (DEN induced hepatic injury in male Wistar albino rats. DEN is an egregious toxin, present in numerous environmental factors, which enhances chemical driven liver damage by inducing oxidative stress and cellular injury. Administration of DEN (200 mg/kg bodyweight, I.P to rats results in elevated marker enzymes (in both serum and tissue. Carvacrol (15 mg/kg body weight suppressed the elevation of marker enzymes (in both serum and tissue and augmented the antioxidants levels. The hoisted activities of Phase I enzymes and inferior activities of Phase II enzymes were observed in DEN-administered animals, whereas Carvacrol treated animals showed improved near normal activity. Histological observations also support the protective role of Carvacrol against DEN induced liver damage. Final outcome from our findings intimate that Carvacrol might be beneficial in attenuating toxin induced liver damage.

  1. Ethyl pyruvate protects against experimental acute-on-chronic liver failure in rats

    Institute of Scientific and Technical Information of China (English)

    Lu-Wen Wang; Li-Kun Wang; Hui Chen; Cheng Fan; Xun Li; Can-Ming He; Zuo-Jiong Gong

    2012-01-01

    AIM:To investigate the protective effects of ethyl pyruvate (EP) on acute-on-chronic liver failure (ACLF) in METHODS:An ACLF model was established in rats,and animals were randomly divided into normal,model and EP treatment groups.The rats in EP treatment group received EP (40 mg/kg) at 3 h,6 h,12 h and 24 h after induction of ACLF.Serum endotoxin,high mobility group box-1 (HMGB1),alanine transaminase (ALT),tumor necrosis factor-α (TNF-α),interferon-α (IFN-y),interleukin (IL)-10 and IL-18 levels,changes of liver histology and HMGB1 expressions in liver tissues were detected at 48 h after induction of ACLF.The effects of EP on the survival of ACLF rats were also observed.RESULTS:Serum levels of endotoxin (0.394 ± 0.066 EU/mL vs 0.086 ± 0.017 EU/mL,P < 0.001),HMGB1 (35.42 ± 10.86 μg/L vs 2.14 ± 0.27 μg/L,P < 0.001),ALT (8415.87 ± 3567.54 IU/L vs 38.64 ± 8.82 IU/L,P < 0.001),TNF-α (190.77 ± 12.34 ng/L vs 124.40 ± 4.12 ng/L,P < 0.001),IFN-γ (715.38 ± 86.03 ng/L vs 398.66 ± 32.91 ng/L,P < 0.001),IL-10 (6.85 ± 0.64ng/L vs 3.49 ± 0.24 ng/L,P < 0.001) and IL-18 (85.19± 3.49 ng/L vs 55.38 ± 1.25 ng/L,P < 0.001) were significantly increased,and liver tissues presented severe pathological injury in the model group compared with the normal group.However,EP administration significantly improved hepatic histopathology and reduced the serum levels of endotoxin (0.155 ± 0.045 EU/mL vs 0.394-0.066 EU/mL,P < 0.001) and inflammatory cytokines (11.13 ± 2.58 μg/L vs 35.42± 10.86 μg/L for HMGB1,3512.86 ± 972.67 IU/L vs 8415.87 ± 3567.54 IU/L for ALT,128.55 ± 5.76 ng/L vs 190.77-12.34 ng/L for TNF-α,438.16 ± 38.10 ng/L vs 715.38 ± 86.03 ng/L for IFN-y,3.55 ± 0.36 ng/L vs 6.85 ± 0.64 ng/L for IL-10,and 60.35 ± 1.63ng/L vs 85.19 ± 3.49 ng/L for IL-18,respectively,P < 0.001),and the levels of HMGB1 in liver tissues regardless of treatment time after induction of ACLF.EP treatment at the four time points prolonged the median survival time

  2. Liver and kidney toxicity in chronic use of opioids: An experimental long term treatment model

    Indian Academy of Sciences (India)

    Sebnem Atici; Ismail Cinel; Leyla Cinel; Nurcan Doruk; Gulcin Eskandari; Ugur Oral

    2005-03-01

    In this study, histopathological and biochemical changes due to chronic usage of morphine or tramadol in liver and kidney were assessed in rats. Thirty male Wistar rats (180–220 g) were included and divided into three groups. Normal saline (1 ml) was given intraperitoneally as placebo in the control group ( = 10). Morphine group ( = 10) received morphine intraperitoneally at a dose of 4, 8, 10 mg/kg/day in the first, second and the third ten days of the study, respectively. Tramadol group ( = 10), received the drug intraperitoneally at doses of 20, 40 and 80 mg/kg/day in the first, second and the third ten days of the study, respectively. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatinin, blood urea nitrogen (BUN) and malondialdehyde (MDA) levels were measured in the serum. Liver and kidney specimens were evaluated by light microscopy. Serum ALT, AST, LDH, BUN and creatinin levels were significantly higher in morphine group compared to the control group. Serum LDH, BUN and creatinin levels were significantly increased in the morphine group compared to the tramadol group. The mean MDA level was significantly higher in morphine group compared to the tramadol and control groups ( < 0.05). Light microscopy revealed severe centrolobular congestion and focal necrosis in the liver of morphine and tramadol groups, but perivenular necrosis was present only in the morphine group. The main histopathologic finding was vacuolization in tubular cells in morphine and tramadol groups. Our findings pointed out the risk of increased lipid peroxidation, hepatic and renal damage due to long term use of opioids, especially morphine. Although opioids are reported to be effective in pain management, their toxic effects should be kept in mind during chronic usage.

  3. Hyperglycemia Aggravates Hepatic Ischemia Reperfusion Injury by Inducing Chronic Oxidative Stress and Inflammation

    Directory of Open Access Journals (Sweden)

    Yihan Zhang

    2016-01-01

    Full Text Available Aim. To investigate whether hyperglycemia will aggravate hepatic ischemia reperfusion injury (HIRI and the underlying mechanisms. Methods. Control and streptozotocin-induced diabetic Sprague-Dawley rats were subjected to partial hepatic ischemia reperfusion. Liver histology, transferase, inflammatory cytokines, and oxidative stress were assessed accordingly. Similarly, BRL-3A hepatocytes were subjected to hypoxia/reoxygenation (H/R after high (25 mM or low (5.5 mM glucose culture. Cell viability, reactive oxygen species (ROS, and activation of nuclear factor-erythroid 2-related factor 2 (Nrf2 and nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB were determined. Results. Compared with control, diabetic rats presented more severe hepatic injury and increased hepatic inflammatory cytokines and oxidative stress. HIRI in diabetic rats could be ameliorated by pretreatment of N-acetyl-L-cysteine (NAC or apocynin. Excessive ROS generation and consequent Nrf2 and NF-κB translocation were determined after high glucose exposure. NF-κB translocation and its downstream cytokines were further increased in high glucose cultured group after H/R. While proper regulation of Nrf2 to its downstream antioxidases was observed in low glucose cultured group, no further induction of Nrf2 pathway by H/R after high glucose culture was identified. Conclusion. Hyperglycemia aggravates HIRI, which might be attributed to chronic oxidative stress and inflammation and potential malfunction of antioxidative system.

  4. Aggravation of symptomatic occipital epilepsy of childhood by carbamazepine

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    Škrijelj Fadil E.

    2014-01-01

    Full Text Available Introduction. Carbamazepine can lead to aggravation of epileptic seizures in generalized epilepsies (primary or secondary with clinical manifestations of absence (typical or atypical and/or myoclonic seizures. However, some focal epilepsies can be also aggravated by the introduction of carbamazepine. Case report. We presented a 10-year-old boy born after a complicated and prolonged delivery completed by vacuum extraction, of early psychomotor development within normal limits. At the age of 8 years he had the first epileptic seizure of simple occipital type with generalization and urination. Brain magnetic resonance imaging (MRI showed focal cortical reductions in the left parietal and occipital regions. Interictal EEG recorded slowed basic activities above the posterior regions of the left hemisphere, with intermittent occurrence of occipital sharp waves and bioccipital sharp and slow-wave complexes. Initially, treatment with valproate was administered; however, the addition of carbamazepine into therapy induced aggravation of seizures and EEG findings, changed behavior and poor performance at school. By withdrawal of carbamazepine the condition improved both clinically and in EEG findings. Conclusion. Childhood occipital epilepsy lesions show deterioration due to carbamazepine, which if administered induces aggravation of seizures, behavior changes, cognition with occurrence of long-term bilateral discharges, and posterior sharp and slow wave high amplitude complexes recorded by EEG.

  5. 38 CFR 3.306 - Aggravation of preservice disability.

    Science.gov (United States)

    2010-07-01

    ... disability. 3.306 Section 3.306 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... Connection § 3.306 Aggravation of preservice disability. (a) General. A preexisting injury or disease will be... disability during such service, unless there is a specific finding that the increase in disability is due...

  6. Inducing and Aggravating Factors of Gastroesophageal Reflux Symptoms

    Directory of Open Access Journals (Sweden)

    Radhiyatam Mardhiyah

    2016-12-01

    Full Text Available Gastroesophageal reflux disease (subsequently abbreviated as GERD is a disease commonly found in the community. Several factors have been recognized as inducing and aggravating factors of GERD symptoms such as older age, female gender, obesity, smoking habit, alcohol consumption, certain diet and poor eating habit like eating fatty, spicy, and acid food.

  7. Metformin increases liver accumulation of vitamin B12 - An experimental study in rats

    DEFF Research Database (Denmark)

    Greibe, E; Miller, J W; Foutouhi, S H;

    2013-01-01

    , and kidneys were collected and analyzed for B(12), unsaturated B(12)-binding capacity, and (57)[Co]-B(12). RESULTS: Three weeks of metformin treatment reduced plasma B(12) by 22% or 289 [47-383] pmol/L (median and [range]) (p = 0.001), while no effect was observed on unsaturated B(12)-binding capacity....... Compared with controls, the amount of B(12) in the liver was 36% (p = 0.007) higher in metformin-treated rats, while the B(12) content in the kidney was 34% (p = 0.013) lower. No difference in the total amount of absorbed (57)[Co]-B(12) present in the tissues and organs studied was found, suggesting...... that metformin has no decreasing effect on the B(12) absorption. CONCLUSIONS/INTERPRETATION: These results show that metformin treatment increases liver accumulation of B(12), thereby resulting in decreases in circulating B(12) and kidney accumulation of the vitamin. Our data questions whether the low plasma B...

  8. Posthemorrhage glycogen and lactate metabolism in the liver: an experimental study with postprandial rats

    Energy Technology Data Exchange (ETDEWEB)

    Boija, P.O.; Nylander, G.; Suhaili, A.; Ware, J.

    1988-06-01

    Glycogen and lactate metabolism was studied in livers from three groups of postprandial rats sustaining 70 mm Hg hemorrhagic hypotension for variable periods, 60 min (60H group), 120 min (120H group), and nonbled controls. The donor livers were investigated after completed hemorrhage using an in vitro perfusion system with L-lactate as substrate, together with U-/sup 14/C-lactate. The residual glycogen stores were determined after perfusions. The incorporation of labelled lactate to glucose was increased in the 120H group by 66.7% and 116.8% compared to the 60H group and controls (p less than 0.01), but glycogenolysis was still the main source of glucose released in the 120H group. Glycogen formation from labelled lactate was 46.6% higher in the 120H group compared to controls (p less than 0.05) and lactate oxidation was decreased by 67.5% (p less than 0.05). The data suggest that hepatocytes are capable of rapid change from glycolysis to gluconeogenesis during hemorrhagic hypovolemia. However, energy-sparing glycogen breakdown is given priority over gluconeogenesis as long as glycogen remains available.

  9. A comparative study on the hepatoprotective action of bear bile and coptidis rhizoma aqueous extract on experimental liver fibrosis in rats

    Directory of Open Access Journals (Sweden)

    Wang Ning

    2012-11-01

    Full Text Available Abstract Aim of the study Bear bile and Coptidis Rhizoma have been used in Chinese medicine with a long tradition in treating heat-diseases. Both bear bile and Coptidis Rhizoma are used to treat liver diseases in clinical practice of Chinese Medicine. Since bears are currently endangered, it raises the question whether the use of bear bile is ethical. To look for substitute for bear bile, the aim of this study is to compare the anti-fibrotic effects of Coptidis Rhizoma and its major component berberine with the actions of bear bile and its major compound tauroursodeoxycholic acid on experimental liver fibrosis in rats. Method Quality assessment was conducted with high performance liquid chromatography. The experimental liver fibrosis in rats was induced by carbon tetrachloride, alcohol, and bile duct ligation respectively. The biochemical criteria in the blood and tissue samples were measured to evaluate the anti-fibrotic properties and underlying mechanisms of the drugs. Results Coptidis Rhizoma Aqueous Extract (CRAE, berberine, and bear bile exerted anti-fibrotic properties on various liver fibrosis models in rats. CRAE and berberine significantly reduced the peroxidative stress in liver through increasing the superoxide dismutase enzyme activity. CRAE and berberine were able to excrete bilirubin products from the liver and protect hepatocytes from cholestatic damage. The effect of CRAE and berberine are comparable to that of bear bile. Conclusion Instead of using bear bile, CRAE and berberine can be potential substitutes in treating liver fibrosis.

  10. [The effect of phospholipid hepatoprotectors on lipid peroxidation in liver and content of cytokines in the blood in experimental pathology caused by isoniazid].

    Science.gov (United States)

    Udut, V V; Vengerovskiĭ, A I; Burkova, V N; Vaizova, O E; Korshunov, D A

    2012-01-01

    The purpose--to investigate the influence of hepatoprotective agents of phospholipids'structure essentiale, eplir and its combinations with amber acid on rats liver functional state, lipoperoxidation and bioenergetics, also tumor necrosis factor-a and interleukin-10 blood content in experimental isoniazid intoxication. These agents demonstrated antioxidant action, decreased the common and indirect bilirubine, tumor necrosis factor-alpha blood content, aminotransferase and alkaline phosphatase activity, increased the interleukin-10 blood content. Isonoazid uncoupled the substrate oxidation with ADP phosphorylation and inhibited the respiratory activity of liver mitochondrions. Essentiale and eplir increased the coupling of oxidation with ATP synthesis, in combination with amber acid improved kinetic characteristics of liver mitochondrions.

  11. New Radiofrequency Device to Reduce Bleeding after Core Needle Biopsy: Experimental Study in a Porcine Liver Model

    Science.gov (United States)

    Lim, Sanghyeok; Lee, Min Woo; Song, Kyoung Doo; Kang, Tae Wook; Kim, Young-sun; Lim, Hyo Keun

    2017-01-01

    Objective To evaluate the in vivo efficiency of the biopsy tract radiofrequency ablation for hemostasis after core biopsy of the liver in a porcine liver model, including situations with bleeding tendency and a larger (16-gauge) core needle. Materials and Methods A preliminary study was performed using one pig to determine optimal ablation parameters. For the main experiment, four pigs were assigned to different groups according to heparinization use and biopsy needle caliber. In each pig, 14 control (without tract ablation) and 14 experimental (tract ablation) ultrasound-guided core biopsies were performed using either an 18- or 16-gauge needle. Post-biopsy bleeding amounts were measured by soaking up the blood for five minutes. The results were compared using the Mann-Whitney U test. Results The optimal parameters for biopsy tract ablation were determined as a 2-cm active tip electrode set at 40-watt with a tip temperature of 70–80℃. The bleeding amounts in all experimental groups were smaller than those in the controls; however they were significant in the non-heparinized pig biopsied with an 18-gauge needle and in two heparinized pigs (p < 0.001). In the heparinized pigs, the mean blood loss in the experimental group was 3.5% and 13.5% of the controls biopsied with an 18- and 16-gauge needle, respectively. Conclusion Radiofrequency ablation of hepatic core biopsy tract ablation may reduce post-biopsy bleeding even under bleeding tendency and using a larger core needle, according to the result from in vivo porcine model experiments. PMID:28096727

  12. Comparative histopathology of the lymph nodes, spleen, liver and kidney in experimental ovine trypanosomosis.

    Science.gov (United States)

    Omotainse, S O; Anosa, V O

    2009-12-01

    The infection of Yankassa rams with three important trypanosome species affecting livestock, namely, Trypanosoma congolense, T. vivax and T. bruceiproduced both acute and chronic fatal conditions. Chronic infections were induced in the three infections by the application of subcurative doses of diaminazene aceturate (Berenil). Pathological changes in the infected animals included splenomegaly and hepatomegaly which were more pronounced in acute than in chronic T. congolense infection. However, these changes were more severe in chronic than in acute T. vivax infection. While splenomegaly was more pronounced in chronic T. bruceiinfection than in acute, hepatomegaly and lymphadenopathy were more severe in acute than in the chronic condition. The increases in size of the spleen, lymph nodes and liver were associated with congestion, increases in cell density related to increased immunological reactions in the spleen and lymph nodes as well as increase in numbers, size and activity of the phagocytic cells in these organs.

  13. Cardioprotective proteins upregulated in the liver in response to experimental myocardial ischemia.

    Science.gov (United States)

    Liu, Shu Q; Tefft, Brandon J; Roberts, Derek T; Zhang, Li-Qun; Ren, Yupeng; Li, Yan Chun; Huang, Yong; Zhang, Di; Phillips, Harry R; Wu, Yu H

    2012-12-15

    Myocardial ischemia (MI) activates innate cardioprotective mechanisms, enhancing cardiomyocyte tolerance to ischemia. Here, we report a MI-activated liver-dependent mechanism for myocardial protection. In response to MI in the mouse, hepatocytes exhibited 6- to 19-fold upregulation of genes encoding secretory proteins, including α-1-acid glycoprotein (AGP)2, bone morphogenetic protein-binding endothelial regulator (BMPER), chemokine (C-X-C motif) ligand 13, fibroblast growth factor (FGF)21, neuregulin (NRG)4, proteoglycan 4, and trefoil factor (TFF)3. Five of these proteins, including AGP2, BMPER, FGF21, NRG4, and TFF3, were identified as cardioprotective proteins since administration of each protein significantly reduced the fraction of myocardial infarcts (37 ± 9%, 34 ± 7%, 32 ± 8%, 39 ± 6%, and 31 ± 7%, respectively, vs. 48 ± 7% for PBS at 24 h post-MI). The serum level of the five proteins elevated significantly in association with protein upregulation in hepatocytes post-MI. Suppression of a cardioprotective protein by small interfering (si)RNA-mediated gene silencing resulted in a significant increase in the fraction of myocardial infarcts, and suppression of all five cardioprotective proteins with siRNAs further intensified myocardial infarction. While administration of a single cardioprotective protein mitigated myocardial infarction, administration of all five proteins furthered the beneficial effect, reducing myocardial infarct fractions from PBS control values from 46 ± 6% (5 days), 41 ± 5% (10 days), and 34 ± 4% (30 days) to 35 ± 5%, 28 ± 5%, and 24 ± 4%, respectively. These observations suggest that the liver contributes to cardioprotection in MI by upregulating and releasing protective secretory proteins. These proteins may be used for the development of cardioprotective agents.

  14. Downregulation of discoidin domain receptor 2 in A375 human melanoma cells reduces its experimental liver metastasis ability.

    Science.gov (United States)

    Badiola, Iker; Villacé, Patricia; Basaldua, Iratxe; Olaso, Elvira

    2011-10-01

    Discoidin domain receptors (DDR1 and DDR2) are tyrosine kinase receptors for fibrillar collagen implicated in postnatal development, tissue repair, and primary and metastatic cancer progression. While DDR1 has been described in tumor cells, DDR2 has been localized in the tumor stroma, but its presence in the tumor cells remains unknown. The aim of this study was to elucidate the role of DDR2 signaling in tumor cells during hepatic metastasis progression. DDR2 expression and phosphorylation in cultured human A375 melanoma cells was documented by Western blot analysis. A375 cells were stably transfected with a small interfering RNA (siRNA) against DDR2 and two clones were selected: A375R2-70 and A375R2-40, with 70 and 40% of the DDR2 protein expression respectively, compared to mock-transfected cells (A375R2-100). Development of experimental liver metastasis by intrasplenic inoculation of A375R2-70 and A37R2-40 clones was reduced by 60 and 75%, respectively, measured as tumor volume, compared to livers injected with A375R2-100 cells. Accordingly, A375R2-70 and A37R2-40 clones showed reduced in vitro gelatinase activity and JNK phosphorylation, compared to mock transfected cells, with maximal inhibition in A375R2-40. Additionally, A375 melanoma, SK-HEP hepatoma and HT-29 colon carcinoma human cell lines transiently transfected with siRNA against DDR2 also showed reduced proliferation and migration rates compared to mock-transfected ones. In conclusion, DDR2 promotes A375 melanoma metastasis to the liver and the underlying mechanism implicates regulation of metalloproteinase release, cell growth and chemotactic invasion of the host tissue.

  15. Basis of aggravated hepatic lipid metabolism by chronic stress in high-fat diet-fed rat.

    Science.gov (United States)

    Han, Ying; Lin, Min; Wang, Xiaobin; Guo, Keke; Wang, Shanshan; Sun, Mengfei; Wang, Jiao; Han, Xiaoyu; Fu, Ting; Hu, Yang; Fu, Jihua

    2015-03-01

    Our previous study has demonstrated that long-term stress, known as chronic stress (CS), can aggravate nonalcoholic fatty liver disease in high-fat diet (HFD)-fed rat. In this study, we tried to figure out which lipid metabolic pathways were impacted by CS in the HFD-fed rat. Male Sprague-Dawley rats (6 weeks of age, n = 8 per group) were fed with either standard diet or HFD with or without CS exposure for 8 weeks. Hepatic lipidosis, biochemical, hormonal, and lipid profile markers in serum and liver, and enzymes involved in de novo lipogenesis (DNL) of fatty acids (FAs) and cholesterol, β-oxidation, FAs uptake, triglycerides synthesis, and very low-density lipoprotein (VLDL) assembly in the liver were detected. CS exposure reduced hepatic lipidosis but further elevated hepatic VLDL content with aggravated dyslipidemia in the HFD-fed rats. There was a synergism between CS and HFD on VLDL production and dyslipidemia. PCR and western blot assays showed that CS exposure significantly promoted hepatic VLDL assembly in rats, especially in the HFD-fed rats, while it had little impact on DNL, β-oxidation, FAs uptake, and triglycerides synthesis in the HFD-fed rats. This phenomenon was in accordance with elevated serum glucocorticoid level. The critical influence of CS exposure on hepatic lipid metabolism in the HFD-fed rats is VLDL assembly which might be regulated by glucocorticoid.

  16. Pathogenesis of liver lesions caused by experimental infection with Piscirickettsia salmonis in juvenile Atlantic salmon, Salmo salar L.

    Science.gov (United States)

    Almendras, F E; Fuentealba, I C; Frederick Markham, R F; Speare, D J

    2000-11-01

    Piscirickettsia salmonis, the etiologic agent of salmonid rickettsial septicemia (SRS), or piscirickettsiosis, causes substantial economic losses to the salmon industry. The pathogenesis of the disease has not been fully characterized. The aim of this study is to describe the hepatic lesions associated with experimental P. salmonis infection in Atlantic salmon juveniles. Fish were maintained in fresh water and inoculated intraperitoneally (IP), orally, or on the gill surface with P. salmonis. A group of uninfected fish was kept as control. Liver samples from 5 fish in each inoculated group and 3 controls were collected weekly and processed for histological and immunohistochemical examination. Thickening of the liver capsule by inflammatory cells was a characteristic histologic feature of IP inoculated fish. Three weeks post-IP inoculation, 8 fish had died and 2 fish were sampled. Histological changes at this time consisted of vasculitis, presence of fibrin thrombi, vacuolated hepatocytes and focal areas of necrosis. Leukocytes containing intracytoplasmic basophilic microorganisms were seen within hepatic sinusoids. Vasculitis and intracytoplasmic vacuoles were prominent features in fish inoculated orally and on the gill surface. The presence of P. salmonis within hepatocellular vacuoles, endothelial cells, and leucocytes was confirmed by immunohistochemistry. The intracellular location of P. salmonis and the vascular damage seen in infected fish are characteristic of rickettsial infections. Histological lesions induced by experimental infection with P. salmonis using the oral and gill surface routes were similar to those observed in natural outbreaks of piscirickettsiosis. The tropism of P. salmonis for endothelial cells explains the vascular lesions observed in SRS, whereas hepatic lesions are due to ischemic necrosis and direct injury by intracytoplasmic organisms.

  17. [Effects of gomisin A, a lignan component of Schizandra fruits, on experimental liver injuries and liver microsomal drug-metabolizing enzymes].

    Science.gov (United States)

    Takeda, S; Maemura, S; Sudo, K; Kase, Y; Arai, I; Ohkura, Y; Funo, S; Fujii, Y; Aburada, M; Hosoya, E

    1986-02-01

    Effects of oral administration of gomisin A, one of the components isolated from Schizandra fruits, on liver injuries induced by CCl4, d-galactosamine and dl-ethionine and on liver microsomal drug-metabolizing enzyme activities were investigated. Gomisin A suppressed the increase of serum transaminase activities and the appearances of histological changes such as degeneration and necrosis of hepatocyte, inflammatory cell infiltration and fatty deposition in each type of liver injury. The repeated administration of gomisin A (30 or 100 mg/kg, p.o., daily for 4 days) induced an apparent increase of liver weight in liver-injured and normal rats. Gomisin A decreased serum triglyceride and lipid contents of the liver in biochemical studies. Increases of microsomal cytochrome b5 and P-450, elevations of NADPH cytochrome C reductase, aminopyrine N-demethylase and 7-ethoxycoumarin O-deethylase activities and decrease of 3,4-benzo(a)pyrene hydroxylase activity per cytochrome P-450 were observed after the administration of gomisin A. In addition, gomisin A was found to enhance the incorporation of 14C-phenylalanine into liver protein and to shorten the hexobarbital-induced sleeping time. These changes caused by gomisin A were similar to those by phenobarbital. However, gomisin A is distinctly different from phenobarbital in the finding that phenobarbital lessened the survival ratio of CCl4-intoxicated mice, but gomisin A did not. Our observation suggest that gomisin A shows an antihepatotoxic action by oral application and also has hypolipidemic (mainly triglyceridemic) and liver protein synthesis-facilitating actions and that the enlargement of the liver seen with gomisin A is the adaptive hypertrophy which is due to the induction of drug-metabolizing enzymes.

  18. Isolation of a novel thermophilic Campylobacter from cases of spotty liver disease in laying hens and experimental reproduction of infection and microscopic pathology.

    Science.gov (United States)

    Crawshaw, Tim R; Chanter, Jeremy I; Young, Stuart C L; Cawthraw, Shaun; Whatmore, Adrian M; Koylass, Mark S; Vidal, Ana B; Salguero, Francisco J; Irvine, Richard M

    2015-09-30

    The condition known as spotty liver disease or spotty liver syndrome can cause significant mortality in free range laying hen flocks. It has been described in Europe and Australia but the aetiology has not been established. There are similarities between spotty liver disease and avian vibrionic hepatitis, a condition which was reported in the 1950s. A Vibrio-like organism was suspected to be the cause of avian vibrionic hepatitis, although this organism was never fully characterised. We report the isolation of a novel Campylobacter from five separate outbreaks of spotty liver disease. The conditions required for culture, the growth characteristics, electron microscopical morphology and results of the phenotypic tests used in the identification of this novel Campylobacter sp. are described. The novel Campylobacter is slow growing and fastidious and does not grow on media routinely used for isolating Campylobacter sp. The morphology is typical for a Campylobacter sp. and phenotypic tests and a duplex real time PCR test differentiate the novel Campylobacter from other members of the genus. 16S rRNA analysis of 19 isolates showed an identical sequence which appears to represent a hitherto unknown sub lineage within the genus Campylobacter. Experimental intraperitoneal infection of four week old SPF chickens produced microscopic liver pathology indistinguishable from natural disease and the novel Campylobacter was recovered from the experimentally infected chicks. The isolates described appear to be a possible causal organism for spotty liver disease.

  19. Aggravating andmitigating factors associated with cyclist injury severity in Denmark

    DEFF Research Database (Denmark)

    Kaplan, Sigal; Vavatsoulas,, Konstantinos; Prato, Carlo Giacomo

    2014-01-01

    Denmark is one of the leading cycling nations, where cycling trips constitute a large share of the total trips, and cycling safety assumes a top priority position in the agenda of policy makers. The current study sheds light on the aggravating and mitigating factors associated with cyclist injury...... severity on Danish roads by examining a comprehensive set of accidents involving a cyclist and a collision partner between 2007 and 2011. Method: This study estimates a generalized ordered logit model of the severity of cyclist injuries because of its ability to accommodate the ordered-response nature...... of severity while relaxing the proportional odds assumption. Results: Model estimates show that cyclist fragility (children under 10 years old and elderly cyclists over 60 years of age) and cyclist intoxication are aggravating individual factors,while helmet use is a mitigating factor. Speed limits above 70...

  20. Aggravated neuromuscular symptoms of mercury exposure from dental amalgam fillings.

    Science.gov (United States)

    Akbal, Ayla; Yılmaz, Hınç; Tutkun, Engin; Köş, Durdu Mehmet

    2014-01-01

    Dental amalgam fillings are widely used all over the world. However, their mercury content can lead to various side effects and clinical problems. Acute or chronic mercury exposure can cause several side effects on the central nerve system, renal and hepatic functions, immune system, fetal development and it can play a role on exacerbation of neuromuscular diseases. In this case, we will present a patient with vacuolar myopathy whose symptoms were started and aggravated with her dental amalgam fillings.

  1. Minimally invasive swine experimental model for the in vivo study of liver metabolism of drugs

    OpenAIRE

    Piazza, Ornella; Romano, Rosalba; Scarpati, Giuliana; Esposito, Ciro; Cavaglià, Enrico; Corona, Marco

    2012-01-01

    Purpose: To develop a clinically relevant porcine model for the study of hepatic metabolism of drugs by means of hepatic vein catheterization. Materials and Methods: review of literature and elaboration of a hypothesis, design of an experimental method. Results: recent clinical studies were conducted by withdrawing cirrhotic patients’ blood from right hepatic vein during hepatic vein pressure gradient measurements. Basing on our personal clinical experience a...

  2. Toll-Like Receptor 3 Gene Deficiency Aggravates Carbon Tetrachloride-Induced Liver Fibrosis in Mice%Toll样受体3基因缺陷促进四氯化碳诱导的小鼠肝纤维化损伤

    Institute of Scientific and Technical Information of China (English)

    薛如意; 张丹瑛; 吴昊; 刘韬韬; 董玲; 沈锡中

    2016-01-01

    使肝组织中炎性因子 TNF‐α、IL‐6和 MCP‐1以及促纤维化分子TGF‐β、TIMP1和PDGFR表达升高。结论:TLR3基因缺陷可促进四氯化碳诱导的肝纤维化小鼠肝组织中的胶原沉积和肝星状细胞激活,促进肝组织炎性因子释放,使肝促纤维化分子上调。以上提示,T L R3是肝纤维化病理过程中的一个保护性基因。%Objective:To investigate the effect of Toll‐like receptor 3(TLR3) gene deficiency on the degree of liver fibrosis in mouse model of carbon tetrachloride(CCl4 )‐induced liver fibrosis .Methods :A total of 20 wild‐type male mice and 20 male mice with TLR3 gene deficiency (TLR3‐/‐) were divided into wild‐type control group and wild‐type model group ,TLR3‐/‐ control group and TLR3‐/‐ model group ,respectively ,with 10 mice in each group .The control group was injected with corn‐oil by intraperitoneal injection while the model group was injected with CCl4 by intraperitoneal injection .After 8 weeks ,blood sample wascollectedandserumlevelofalanineaminotransferase(ALT),aspartatetransaminase(AST),totalbilirubin(TBIL),and albumin(Alb) was analyzed by automatic biochemical analyzer .And the degree of collagen deposition in liver tissue was evaluated by Masson trichrome staining .And the activation of hepatic stellate cells was detected by immunohistochemistry staining of α‐smooth muscle actin(α‐SMA).And hydroxyproline content of liver tissue was detected with detection kit . Furthermore ,real‐time fluorescence polymerase chain reaction was used to detect the expression of liver fibrotic marker type I collagen ,and inflammatory cytokines including tumor necrosis factor‐alpha (TNF‐α) , interleukin‐6 (IL‐6 ) and monocyte chemotactic protein‐1(MCP‐1) ,as well as pro‐fibrotic molecule including transforming growth factor‐beta (TGF‐β) ,tissue inhibitor of metalloproteinase 1(TIMP1) and platelet‐derived growth factor receptor(PDGFR) .Results:TLR3 gene deficiency had no

  3. C57BL/6 and A/J Mice Have Different Inflammatory Response and Liver Lipid Profile in Experimental Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Lorena Bavia

    2015-01-01

    Full Text Available Alcoholic liver disease (ALD is an important worldwide public health issue characterized by liver steatosis, inflammation, necrosis, and apoptosis of hepatocytes with eventual development of fibrosis and cirrhosis. Comparison of murine models with different inflammatory responses for ALD is important for an evaluation of the importance of genetic background in the interpretation of ethanol-induced phenotypes. Here, we investigated the role of inflammation and genetic background for the establishment of ALD using two different mouse strains: C57BL/6 (B6 and A/J. B6 and A/J mice were treated with a high fat diet containing ethanol (HFDE and compared to the controls for 10 weeks. Hepatomegaly and steatohepatitis were similar in B6 and A/J mice, but only A/J mice were resistant to weight gain. On the other hand, HFDE-fed B6 accumulated more triglycerides (TG and cholesterol and presented more intense cellular infiltrate in the liver when compared to HFDM-fed mice. Liver inflammatory environment was distinct in these two mouse strains. While HFDE-fed B6 produced more liver IL-12, A/J mice increased the TNF-α production. We concluded that mouse genetic background could dictate the intensity of the HFDE-induced liver injury.

  4. Anti-hepatoma effect of arsenic trioxide on experimental liver cancer induced by 2-acetamidofiuorene in rats

    Institute of Scientific and Technical Information of China (English)

    Bing Tan; Jie-Fei Huang; Qun Wei; Hong Zhang; Run-Zhou Ni

    2005-01-01

    AIM: To study the anti-hepatoma efficiency of arsenic trioxide (As2O3) in the treatment of experimental rat hepatocellular carcinoma (HCC) induced by 2-acetamidofluorene (2-FAA)and to elucidate the possible mechanisms.METHODS: SD rats (2 mo old) had been fed with 2-FAA for 8 wk to induce HCC, and then they were treated with As2O3 or matrine. On d 29, the rats were killed and the liver was weighed and liver tumors were counted. The histological changes of liver tissue were observed under microscope, and the cellular dynamic parameters were studied by flow cytometry. Immunohistochemistry (two-step method) was used to observe the expression of vascular endothelial growth factor (VEGF) and micro-vessel density (MVD) on consecutive sections. The pathological parameters were also analyzed, the levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT),total bilirubin (TBi), and direct bilirubin (DBi).RESULTS: The number of liver tumors decreasedsignificantly in groups treated with As2O3, especially in medium-dose (1 mg/kg) group (t = 2.80, P<0.01). As2O3 caused HCC cell death via apoptosis; necrosis was seen and apoptosis was common when the dose was 1 mg/kg.Proliferation index decreased sharply in medium-dose (1 mg/kg) group (7.87±4.11 vs 24.46±6.49, t = 2087,P<0.01), but not in 0.2 mg/kg group. However, S-phase fraction decreased dramatically in both groups, it reached the bottom level only when the dose was 1 mg/kg compared with control (0.40±0.13 vs 3.01±0.51, t = 2.97, P<0.01),and it was obviously accompanied with accumulation of cells in G0/G± (G0/G1 restriction). The expressions of VEGF and MVD in medium-dose (1 mg/kg) group were significantly lower than normal saline group (0.63±0.74 vs 2.44±0.88, P<0.05; 15.75±3.99 vs47.44±13.41, t= 2.80,P<0.01). Compared with normal saline group, mediumand low-dose groups As2O3 and matrine lowered the levels of ALT in serum (61.46±9.46, 63.75±20.40, 61.18±13.00 vs 108.98±29.86, t= 2

  5. Experimentally nonylphenol-polluted diet induces the expression of silent genes VTG and ER{alpha} in the liver of male lizard Podarcis sicula

    Energy Technology Data Exchange (ETDEWEB)

    Verderame, Mariailaria; Prisco, Marina; Andreuccetti, Piero [Department of Biological Sciences, Evolutionary and Comparative Biology Division, University Federico II of Naples, Via Mezzocannone 8, 80134 Naples (Italy); Aniello, Francesco [Department of Biological Sciences, Genetic and Molecular Biology Division, University Federico II of Naples, Via Mezzocannone 8, 80134 Naples (Italy); Limatola, Ermelinda, E-mail: limatola@unina.it [Department of Biological Sciences, Evolutionary and Comparative Biology Division, University Federico II of Naples, Via Mezzocannone 8, 80134 Naples (Italy)

    2011-05-15

    Endocrine Disruptor Chemicals (EDCs) with estrogen-like properties i.e nonylphenol (NP) induce vitellogenin (VTG) synthesis in males of aquatic and semi-aquatic specie. In the oviparous species VTG is a female-specific oestrogen dependent protein. Males are unable to synthesize VTG except after E{sub 2} treatment. This study aimed to verify if NP, administered via food and water, is able to induce the expression of VTG even in males of vertebrates with a terrestrial habitat such as the lizard Podarcis. By means of ICC, ISH, W/B and ELISA we demonstrated that NP induces the presence of VTG in the plasma and its expression in the liver. VTG, undetectable in untreated males, reaches the value of 4.34 {mu}g/{mu}l in the experimental ones. Expression analysis and ISH in the liver showed that an NP-polluted diet also elicits the expression of ER{alpha} in the liver which is known to be related to VTG synthesis in Podarcis. - Highlights: > Nonylphenol (NP) polluted diet induces VTG synthesis in a terrestrial vertebrate. > VTG and ER{alpha} genes are unexpressed in the liver of untreated male lizards Podarcis. > In the liver cells of NP-treated males the expression of both VTG and ER{alpha} occurs. > In treated males VTG synthesis is coupled with ER{alpha} expression as in breeding females. - NP-polluted diet induces the expression of ER{alpha} and VTG in the liver.

  6. EVALUATION OF CIRRHOTIC LIVER WITH PERFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING: A PRELIMINARY EXPERIMENTAL STUDY IN ANIMAL MODELS WITH HALF-LIVER CIRRHOSIS

    Institute of Scientific and Technical Information of China (English)

    Zheng-han Yang; Xiao-hua Ye; Ye Tan; Min Zhang; Ming-zhu Zhou; Jing-xia Xie; Min Chen; Cheng Zhou

    2006-01-01

    Objective To investigate the role of perfusion-weighted magnetic resonance imaging (MRI) in evaluation of cirrhotic liver.Methods With a 4F catheter,1% diluted carbon tetrachloride (1 ml/kg) was selectively injected into right or left hepatic artery of 12 dogs fortnightly.The half liver into which carbon tetrachloride was injected was called as study side (SS),while the other half liver without carbon tetrachloride injection was called as study control side (SCS).Conventional and perfusion-weighted MRI were performed in every 4 weeks.Via a 4F catheter,5ml gadolinium diethylentriamine pentaaceti acid (Gd-DTPA) dilution was injected into superior mesenteric artery at the 5th scan.The signal intensity-time curves of SS,SCS,and portal vein were completed in MR workstation.The maximal relative signal increase (MRSI),peak time (tp),and slope of the curves were measured.Results On conventional MR images,no abnormalities of externality and signal intensity were observed in both SS and SCS of liver at each stage.The mean tp,MRSI,and slope of intensity-time curves in normal liver were 10.56 seconds,1.01,and 10.23 arbitrary unit (au)/s,respectively.Three parameters of curves didn't show obvious change in SCS of liver at every stage.Abnormal perfusion curves occurred in SS of liver at the 12th week after the 1st injection.The abnormality of perfusion curve in SS was more and more serious as the times of injection increased.The mean tp,MRSI,and slope intensity-time curves in SS of liver were 19.45 seconds,0.43,and 3.60 au/s respectively at the 24th week.Conclusion Perfusion-weighted imaging can potentially provide information about portal perfusion of hepatic parenchyma,and to some degree,reflect the severity of cirrhosis.

  7. Effect of various antidotes on biliary excretion of arsenic in isolated perfused livers of guinea pigs after acute experimental poisoning with As2O3.

    Science.gov (United States)

    Reichl, F X; Mückter, H; Kreppel, H; Forth, W

    1992-05-01

    The effect of the dithiols British Anti-Kewisite (BAL), dimercaptopropanesulfonic acid (DMPS), dimercaptosuccinic acid (DMSA) and a new metal binding agent 2,3-bis-(acetylthio)- propanesulfonamide (BAPSA) on the biliary excretion of arsenic in perfused livers of guinea pigs after acute experimental poisoning with As2O3 was investigated. Guinea pigs received As2O3, 10.0 mg/kg subcutaneously at 9 a.m. as a single injection. One hour after the injection the livers were perfused (2.5 ml x min.-1 x g-1 liver) with Krebs-Henseleit buffer and glucose for 80 min. After 40 min. of saline perfusion (control) 0.1 or 0.7 mmol/l BAL, DMSA, DMPS, or BAPSA were added to the perfusate and arsenic elimination in the bile and effluent perfusate was measured. The biliary excretion of arsenic in control livers between 40 and 80 min. was 0.7% of the total arsenic liver content before perfusion (= arsenic liver content after perfusion + portion excreted in the bile+perfusate). After antidote addition (0.1 mmol/l) the excretion was 0.2% for livers perfused with BAL, 6.8% for DMSA, 10.6% for DMPS, and 11.1% for BAPSA, respectively. After 0.7 mmol/l antidote the excretion of arsenic was 0.1% in livers perfused with BAL, 9.6% for DMSA, 12.3% for DMPS, and 13.3% for BAPSA, respectively. Except BAL, all compounds and most effectively BAPSA increased biliary excretion of arsenic. This indicates that excretion of arsenic which normally is mainly renal is shifted towards faecal excretion by the dithiols.

  8. [Effect of Arnica montana on the state of lipid peroxidation and protective glutathione system of rat liver in experimental toxic hepatitis].

    Science.gov (United States)

    Iamemiĭ, I M; Grygor'iea, N P; Meshchyshen, I F

    1998-01-01

    Effects of Tinctura Arnica on lipids peroxidation and on the protective glutathions system of liver in rats in case of experimental toxic hepatitis have been studied. Toxic hepatitis is accompanied by deep alterations of the oxidant-antioxidant status of the body. Intoxication of the body by CCl4 results in intensification of the free radicals formation particularly in liver: accumulation of lipids peroxidation molecular products, glutathione system enzyme activity inhibition in early terms and its partial restoration in remote terms has been seen. Our studies revealed that Arnica montana infusion inhibits the rate of lipids perioxidation products formation, affects the glutathione system enzymes activity.

  9. Liver transplant

    Science.gov (United States)

    Hepatic transplant; Transplant - liver; Orthotopic liver transplant; Liver failure - liver transplant; Cirrhosis - liver transplant ... The donated liver may be from: A donor who has recently died and has not had liver injury. This type of ...

  10. Fiber-Optic Temperature and Pressure Sensors Applied to Radiofrequency Thermal Ablation in Liver Phantom: Methodology and Experimental Measurements

    Directory of Open Access Journals (Sweden)

    Daniele Tosi

    2015-01-01

    Full Text Available Radiofrequency thermal ablation (RFA is a procedure aimed at interventional cancer care and is applied to the treatment of small- and midsize tumors in lung, kidney, liver, and other tissues. RFA generates a selective high-temperature field in the tissue; temperature values and their persistency are directly related to the mortality rate of tumor cells. Temperature measurement in up to 3–5 points, using electrical thermocouples, belongs to the present clinical practice of RFA and is the foundation of a physical model of the ablation process. Fiber-optic sensors allow extending the detection of biophysical parameters to a vast plurality of sensing points, using miniature and noninvasive technologies that do not alter the RFA pattern. This work addresses the methodology for optical measurement of temperature distribution and pressure using four different fiber-optic technologies: fiber Bragg gratings (FBGs, linearly chirped FBGs (LCFBGs, Rayleigh scattering-based distributed temperature system (DTS, and extrinsic Fabry-Perot interferometry (EFPI. For each instrument, methodology for ex vivo sensing, as well as experimental results, is reported, leading to the application of fiber-optic technologies in vivo. The possibility of using a fiber-optic sensor network, in conjunction with a suitable ablation device, can enable smart ablation procedure whereas ablation parameters are dynamically changed.

  11. Aldosterone aggravates glucose intolerance induced by high fructose.

    Science.gov (United States)

    Sherajee, Shamshad J; Rafiq, Kazi; Nakano, Daisuke; Mori, Hirohito; Kobara, Hideki; Hitomi, Hirofumi; Fujisawa, Yoshihide; Kobori, Hiroyuki; Masaki, Tsutomu; Nishiyama, Akira

    2013-11-15

    We previously reported that aldosterone impaired vascular insulin signaling in vivo and in vitro. Fructose-enriched diet induces metabolic syndrome including hypertension, insulin resistance, hyperlipidemia and diabetes in animal. In the current study, we hypothesized that aldosterone aggravated fructose feeding-induced glucose intolerance in vivo. Rats were divided into five groups for six-week treatment; uninephrectomy (Unx, n=8), Unx+aldosterone (aldo, 0.75 µg/h, s.c., n=8), Unx+fructose (fruc, 10% in drinking water, n=8), Unx+aldo+fruc, (aldo+fruc, n=8), and Unx+aldo+fruc+spironolactone, a mineralocorticoid receptor antagonist (aldo+fruc+spiro, 20mg/kg/day, p.o., n=8). Aldo+fruc rats manifested the hypertension, and induced glucose intolerance compared to fruc intake rats assessed by oral glucose tolerance test, homeostasis model assessment of insulin resistance and hyperinsulinemic-euglycemic clamp study. Spironolactone, significantly improved the aldosterone-accelerated glucose intolerance. Along with improvement in insulin resistance, spironolactone suppressed upregulated mineralocorticoid receptor (MR) target gene, serum and glucocorticoid-regulated kinases-1 mRNA expression in skeletal muscle in aldo+fruc rats. In conclusion, these data suggested that aldosterone aggravates fructose feeding-induced glucose intolerance through MR activation.

  12. Beyond bullying: Aggravating elements of peer victimization episodes.

    Science.gov (United States)

    Turner, Heather A; Finkelhor, David; Shattuck, Anne; Hamby, Sherry; Mitchell, Kimberly

    2015-09-01

    This study sought to identify features of peer victimization that aggravate negative outcomes in children. The features that were assessed include "power imbalance," a commonly used criterion in defining bullying, and 5 other characteristics: injury, weapon involvement, Internet involvement, sexual content, and bias content. Three outcomes were assessed: level of fear, missing school, and trauma symptoms. A nationally representative sample of 3,164 children and youth ages 6-17 (51.8% male; 68.4% white, 12.5% black, 13.5% Hispanic, 5.7% other race) was obtained through Random Digit Dial and supplemented with an address-based sample to capture cell-phone-only households. One child was randomly selected from each household. Interviews were conducted with parents of children age 6-9 and with the youths themselves if they were age 10-17. Peer victimization was assessed with the Juvenile Victimization Questionnaire (JVQ). Almost half (48.4%) of the entire sample of school-age children experienced at least 1 form of peer victimization in the past year. Injury and power imbalance independently increased the impact on children for all 3 outcomes. Additionally, weapon involvement and sexual content were associated with trauma symptoms, with sexual content having the strongest effect (B = .23, p bullying with its exclusionary power imbalance definition as the central focus for prevention and intervention. We recommend a broader focus on peer victimization along with more research to identify the aggravating features that signal the greatest need for intervention.

  13. Dual protective role of HO-1 in transplanted liver grafts: A review of experimental and clinical studies

    Institute of Scientific and Technical Information of China (English)

    Chun-Feng Wang; Zhen-Yu Wang; Ji-Yu Li

    2011-01-01

    Liver transplantation is considered as the most effective treatment for end-stage liver disease. However, serious complications still exist, particularly in two aspects: ischemia and subsequent reperfusion of the liver, causing postoperative hepatic dysfunction and even failure; and acute and chronic graft rejections, affecting the allograft survival. Heme oxygenase (HO), a stressresponse protein, is believed to exert a protective function on both the development of ischemia-reperfusion injury (IRI) and graft rejection. In this review of current researches on allograft protection, we focused on the HO-1. We conjecture that HO-1 may link these two main factors affecting the prognosis of liver transplantations. In this review, the following aspects were emphasized: the basic biological functions of HO-1, its roles in IRI and allograft rejection, as well as methods to induce HO-1 and the prospects of a therapeutic application of HO-1 in liver transplantation.

  14. Microbiological safety of a novel bio-artificial liver support system based on porcine hepatocytes: a experimental study

    Directory of Open Access Journals (Sweden)

    Han Bing

    2012-05-01

    Full Text Available Abstract Background Our institute has developed a novel bio-artificial liver (BAL support system, based on a multi-layer radial-flow bioreactor carrying porcine hepatocytes and mesenchymal stem cells. It has been shown that porcine hepatocytes are capable of carrying infectious porcine endogenous retroviruses (PERVs into human cells, thus the microbiological safety of any such system must be confirmed before clinical trials can be performed. In this study, we focused on assessing the status of PERV infection in beagles treated with the novel BAL. Methods Five normal beagles were treated with the novel BAL for 6 hours. The study was conducted for 6 months, during which plasma was collected from the BAL and whole blood from the beagles at regular intervals. DNA and RNA in both the collected peripheral blood mononuclear cells (PBMCs and plasma samples were extracted for conventional PCR and reverse transcriptase (RT-PCR with PERV-specific primers and the porcine-specific primer Sus scrofa cytochrome B. Meanwhile, the RT activity and the in vitro infectivity of the plasma were measured. Results Positive PERV RNA and RT activity were detected only in the plasma samples taken from the third circuit of the BAL system. All other samples including PBMCs and other plasma samples were negative for PERV RNA, PERV DNA, and RT activity. In the in vitro infection experiment, no infection was found in HEK293 cells treated with plasma. Conclusions No infective PERV was detected in the experimental animals, thus the novel BAL had a reliable microbiological safety profile.

  15. Short-term air pollution exposure aggravates Parkinson’s disease in a population-based cohort

    Science.gov (United States)

    Lee, Hyewon; Myung, Woojae; Kim, Doh Kwan; Kim, Satbyul Estella; Kim, Clara Tammy; Kim, Ho

    2017-01-01

    Increasing experimental evidence has suggested air pollution as new risk factor for neurological disease. Although long-term exposure is reportedly related to neurological disease, information on association with short-term exposure is scarce. We examined the association of short-term exposure to particles Health Insurance Service–National Sample Cohort, Korea during 2002–2013. PD aggravation cases were defined as emergency hospital admissions for primarily diagnosed PD and analyzed with a case-crossover analysis, designed for rare acute outcomes. Pollutants concentrations on case and control days were compared and effect modifications were explored. A unit increase in 8-day moving average of concentrations was significantly associated with PD aggravation. The association was consistent for PM2.5 (odds ratio [95% confidence interval]: 1.61 [1.14–2.29] per 10 μg/m3), NO2 (2.35 [1.39–3.97] per 10 ppb), SO2 (1.54 [1.11–2.14] per 1 ppb), and CO (1.46 [1.05–2.04] per 0.1 ppm). The associations were stronger in women, patients aged 65–74 years, and cold season, but not significant. In conclusion, short-term air pollution exposure increased risk of PD aggravation, and may cause neurological disease progression in humans. PMID:28300224

  16. Structural policy in the context of international competition aggravation

    Directory of Open Access Journals (Sweden)

    Volodymyr Bodrov

    2014-09-01

    Full Text Available This article researches the essence and peculiarities of the structural policy, performs classification of its models and determines possibilities of their use in the context of increasing international competition. It discovers the main components of the economic structure and trends of the state policy regarding their modernization. Measures on improvement of state regulation instruments are offered, factors of influence upon improvement of the Ukrainian economy structure are analyzed and priority goals are systematized which require urgent implementation in the terms of competitive struggle aggravation at the global markets. The article also researches the matter of importance of performing a complex of state functional and selective measures in the form of matrix policy for the purpose of protecting national interests of the country in the context of global challenges

  17. Impairment of exogenous lactate clearance in experimental hyperdynamic septic shock is not related to total liver hypoperfusion

    NARCIS (Netherlands)

    P. Tapia (Pablo); D. Soto (Dagoberto); A. Bruhn (Alejandro); L. Alegría (Leyla); N. Jarufe (Nicolás); C. Luengo (Cecilia); E. Kattan (Eduardo); T. Regueira (Tomas); A. Meissner (Arturo); R. Menchaca (Rodrigo); M.I. Vives (María Ignacia); N. Echeverría (Nicolas); G.A. Ospina-Tascon (Gustavo A); J. Bakker (Jan); G. Hernandez (Glenn)

    2015-01-01

    textabstractIntroduction: Although the prognostic value of persistent hyperlactatemia in septic shock is unequivocal, its physiological determinants are controversial. Particularly, the role of impaired hepatic clearance has been underestimated and is only considered relevant in patients with liver

  18. Aggravated Cardiac Remodeling post Aortocaval Fistula in Unilateral Nephrectomized Rats.

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    Jie Wu

    Full Text Available Aortocaval fistula (AV in rat is a unique model of volume-overload congestive heart failure and cardiac hypertrophy. Living donor kidney transplantation is regarded as beneficial to allograft recipients and not particularly detrimental to the donors. Impact of AV on animals with mild renal dysfunction is not fully understood. In this study, we explored the effects of AV in unilateral nephrectomized (UNX rats.Adult male Sprague-Dawley (SD rats were divided into Sham (n = 10, UNX (right kidney remove, n = 10, AV (AV established between the levels of renal arteries and iliac bifurcation, n = 18 and UNX+AV (AV at one week after UNX, n = 22, respectively. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, fractional excretion of sodium, albuminuria, plasma creatinine, and cystatin C. Focal glomerulosclerosis (FGS incidence was evaluated by renal histology. Cardiac function was measured by echocardiography and hemodynamic measurements.UNX alone induced compensatory left kidney enlargement, increased plasma creatinine and cystatin C levels, and slightly reduced glomerular filtration rate and increased FGS. AV induced significant cardiac enlargement and hypertrophy and reduced cardiac function and increased FGS, these changes were aggravated in UNX+AV rats.Although UNX only induces minor renal dysfunction, additional chronic volume overload placement during the adaptation phase of the remaining kidney is associated with aggravated cardiac dysfunction and remodeling in UNX rats, suggesting special medical care is required for UNX or congenital monokidney subjects in case of chronic volume overload as in the case of pregnancy and hyperthyroidism to prevent further adverse cardiorenal events in these individuals.

  19. Energetic, oxidative and ionic exchange in rat brain and liver mitochondria at experimental audiogenic epilepsy (Krushinsky-Molodkina model).

    Science.gov (United States)

    Venediktova, Natalya I; Gorbacheva, Olga S; Belosludtseva, Natalia V; Fedotova, Irina B; Surina, Natalia M; Poletaeva, Inga I; Kolomytkin, Oleg V; Mironova, Galina D

    2017-01-09

    The role of brain and liver mitochondria at epileptic seizure was studied on Krushinsky-Molodkina (KM) rats which respond to sound with an intensive epileptic seizure (audiogenic epilepsy). We didn't find significant changes in respiration rats of brain and liver mitochondria of KM and control rats; however the efficiency of АТР synthesis in the KM rat mitochondria was 10% lower. In rats with audiogenic epilepsy the concentration of oxidative stress marker malondialdehyde in mitochondria of the brain (but not liver) was 2-fold higher than that in the control rats. The rate of H2O2 generation in brain mitochondria of КМ rats was twofold higher than in the control animals when using NAD-dependent substrates. This difference was less pronounced in liver mitochondria. In KM rats, the activity of mitochondrial ATP-dependent potassium channel was lower than in liver mitochondria of control rats. The comparative study of the mitochondria ability to retain calcium ions revealed that in the case of using the complex I and complex II substrates, permeability transition pore is easier to trigger in brain and liver mitochondria of KM and КМs rats than in the control ones. The role of the changes in the energetic, oxidative, and ionic exchange in the mechanism of audiogenic epilepsy generation in rats and the possible correction of the epilepsy seizures are discussed.

  20. STAT3, a Key Parameter of Cytokine-driven Tissue Protection During Sterile Inflammation – the Case of Experimental Acetaminophen (Paracetamol-induced Liver Damage

    Directory of Open Access Journals (Sweden)

    Heiko eMühl

    2016-05-01

    Full Text Available Acetaminophen (APAP, N-acetyl-p-aminophenol, or paracetamol overdosing is a prevalent cause of acute liver injury. While clinical disease is initiated by overt parenchymal hepatocyte necrosis in response to the analgetic, course of intoxication is substantially influenced by associated activation of innate immunity. This process is supposed to be set in motion by release of danger associated molecular patterns (DAMPs from dying hepatocytes and is accompanied by an inflammatory cytokine response. Murine models of APAP-induced liver injury emphasize the complex role that DAMPs and cytokines play in promoting either hepatic pathogenesis or resolution and recovery from intoxication. Whereas the function of key inflammatory cytokines is controversially discussed, a subclass of specific cytokines capable of efficiently activating the hepatocyte signal transducer and activator of transcription (STAT-3 pathway stands out as being consistently protective in murine models of APAP intoxication. Those include foremost interleukin (IL-6, IL-11, IL-13, and IL-22. Above all, activation of STAT3 under the influence of these cytokines has the capability to drive hepatocyte compensatory proliferation, a key principle of the regenerating liver. Herein, the role of these specific cytokines during experimental APAP-induced liver injury is highlighted and discussed in a broader perspective. In hard-to-treat or at-risk patients standard therapy may fail and APAP intoxication can proceed towards a fatal condition. Focused administration of recombinant STAT3-activating cytokines may evolve as novel therapeutic approach under those ill-fated conditions.

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

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    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.

  2. Experimental study on inhibitory effect of bridgy duct of hepatic artery on apoptosis of liver and bile duct cells

    Institute of Scientific and Technical Information of China (English)

    Hongwei Lu; Yiming Li; Hong Ji; Jinkai Xu

    2006-01-01

    Objective: To investigate whether the method of bridgy duct established between the recipient's spleen artery and the donor's gastroduodenal artery could inhibit the apoptosis of liver and bile duct cells caused by hepatic artery ischemia.Methods: Twenty-four mongrel dogs from Xi'an area were used to establish simplified models of dog orthotopic liver transplantation and divided into three groups randomly: HAI group (hepatic artery ischemia group),BBB group (bypassing the blood by a bridgy duct) and control group. After cold perfusion, The samples were collected from liver and bile duct in each group at different time and fixed in glutaraldehyde and 4% polyformaldehyde respectively. At last, the apoptosis of liver and bile duct cells were observed and the apoptotic indexes were calculated. Results: Two hours after cold perfusion, apoptotic phenomenon was common in HAI group, rare in BBB group, while no apoptotic phenomenon was observed in control group. TUNEL staining showed that there was no significant difference in apoptotic index among the three groups immediately after cold perfusion. However, with time going, the apoptotic cells were increased in three groups, and the difference in apoptotic index was significant among three groups (P < 0.01 ). Conclusion: Bridgy duct of hepatic artery can inhibit the apoptosis of liver and bile duct cells caused by HAI significantly.

  3. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970345 An experimental and clinical study on α1-adrenergic receptor of liver plasma membranes in cir-rhosis with portal hypertension. ZHANG Youcheng(张有成), et al. Dept Surg, People’s Hosp, Beijing MedUniv, Beijing, 100044 Chin J Dig 1996; 16(6): 332-335.

  4. [First experience of a polyurethane foam composition "Locus" use to stop intra-abdominal hemorrhage as a result of liver damage of V degree. (An experimental study)].

    Science.gov (United States)

    Reva, V A; Litinskii, M A; Denisov, A V; Sokhranov, M V; Telitskii, S Yu; Samokhvalov, I M

    2015-04-01

    Today self-expanding polymers are considered as the most promising as means for intracavitary hemostasis in case of continuing bleeding after trauma. Testing of domestic open-cell polyurethane foam composition "Locus" was carried out on the developed experimental model simulating liver trauma of V degree. After damaging 6 experimental rabbits were injected intraperitoneally with 80 ml of the composition. 5 experimental rabbits were included into to control group (haemostatic agent was not given). Estimated blood loss was 111-124 ml. The two-hour survival rate didn't differ significantly: 3 animals survived in the experimental group; 2 animal survived in the control. Despite the 3-4-fold widening of the foam, due to open cells it absorbed 72.6 +/- 8.3 g of blood. Thus, open-cell polyurethane foam intraperitoneal administration of the composition didn't provide a temporary intra-abdominal hemostasis in liver. In order to enhance the hemostatic effect it requires changing the formulation of the polyurethane composition. For a more accurate assessment of the results it is neccessary to perform additional researches on larger animals.

  5. Nonalcoholic Fatty Liver Disease: Correlation of the Liver Parenchyma Fatty Acid with Intravoxel Incoherent Motion MR Imaging-An Experimental Study in a Rat Model.

    Directory of Open Access Journals (Sweden)

    Seung-Man Yu

    Full Text Available To prospectively evaluate the changes in fatty acid concentration after administrating a 60% high-fat diet to a non-alcoholic fatty liver disease rat model and to perform a correlation analysis between fatty acid with molecular diffusion (Dtrue, perfusion-related diffusion (Dfast, and perfusion fraction (Pfraction.This prospective study was approved by the appropriate ethics committee. Ten male Sprague-Dawley rats were fed a 60% high-fat diet until the study was finished. Point-resolved spectroscopy sequence 1H-MRS with TR = 1,500 msec, TE = 35 msec, NEX = 64, and 8×8×8 mm3 voxel was used to acquire magnetic resonance spectroscopy (MRS data. Diffusion-weighted imaging was performed on a two-dimensional multi-b value spin echo planar image with the following parameters: repetition time msec/echo time msec, 4500 /63; field of view, 120×120 msec2; matrix, 128×128; section thickness, 3 mm; number of repetition, 8; and multiple b value, 0, 25, 50, 75, 100, 200, 500, 1000 sec/mm2. Baseline magnetic resonance imaging and magnetic resonance spectroscopy data (control were acquired. 1H proton MRS and diffusion-weighted imaging were obtained every 2 weeks for 8 weeks. The individual contributions of the true molecular diffusion and the incoherent motions of water molecules in the capillary network to the apparent diffusion changes were estimated using a least-square nonlinear fitting in MatLab. A Wilcoxon signed-rank test with the Kruskal-Wallis test was used to compare each week's fatty acid mean quantification. Spearman's correlation coefficient was used to evaluate the correlation between each fatty acid (e.g., total lipid (TL, total saturated fatty acid (TSFA, total unsaturated fatty acid (TUSFA, total unsaturated bond (TUSB, and polyunsaturated bond (PUSB and intravoxel incoherent motion (IVIM mapping images (e.g., Dtrue, Dfast, and Pfraction.The highest mean TL value was at week 8 (0.278 ± 0.10 after the administration of the 60% high-fat diet

  6. [Abdominal tomometry. Application to study of the liver. Experimental study, initial clinical results and perspectives in the exploration of tumour pathology (author's transl)].

    Science.gov (United States)

    Lamarque, J L; Bruel, J M; Dondelinger, R; Sénac, J P; Rabischong, P; Bonnel, F; Laval-Jeantet, M; Laval-Jeantet, A M

    1977-04-01

    Over a period of two months, 120 patients were studied using an Acta-Scanner tomometer for various hepatic disorders. In parallel, comparative tomometric and pathological studies were carried out in cadavers and isolated livers. These made possible the recognition of normal structures in tomometry and the identification of certain hepatic images which might be potential sources of error. Serial axial transverse sections were used to reconstruct the volume of the liver in space, thus making in possible to eliminate certain forms of pseudo-tumoural hepatomegaly. Systematic densitometric analysis was made by radiological anatomical study and in hepatic pathology. This new type of analysis led to a quantified diagnosis of certain diffuse hepatic diseases and a histological approach to tumour lesions. Hepatography using liposoluble agents in very low dosage was used in hepatic tomometry after animal experimentation. The method, free of untoward effects, makes possible the diagnosis of hepato-splenic tumor lesions less than one centimetre in diameter.

  7. Vitamin D depletion aggravates hypertension and target-organ damage

    DEFF Research Database (Denmark)

    Andersen, Louise Bjørkholt; Przybyl, Lukasz; Haase, Nadine;

    2015-01-01

    BACKGROUND: We tested the controversial hypothesis that vitamin D depletion aggravates hypertension and target-organ damage by influencing renin. METHODS AND RESULTS: Four-week-old double-transgenic rats (dTGR) with excess angiotensin (Ang) II production due to overexpression of the human renin (h......REN) and angiotensinogen (hAGT) genes received vitamin D-depleted (n=18) or standard chow (n=15) for 3 weeks. The depleted group had very low serum 25-hydroxyvitamin D levels (mean±SEM; 3.8±0.29 versus 40.6±1.19 nmol/L) and had higher mean systolic BP at week 5 (158±3.5 versus 134.6±3.7 mm Hg, P....6±3.3 versus 162.3±3.8 mm Hg, PVitamin D depletion led to increased relative heart weights and increased serum creatinine concentrations. Furthermore, the mRNAs of natriuretic peptides, neutrophil gelatinase-associated lipocalin, hREN, and r...

  8. Pain in Breast Cancer Treatment: Aggravating Factors and Coping Mechanisms

    Directory of Open Access Journals (Sweden)

    Maria de Fatima Guerreiro Godoy

    2014-01-01

    Full Text Available The objective of this study was to evaluate pain in women with breast cancer-related lymphedema and the characteristics of aggravating factors and coping mechanisms. The study was conducted in the Clinica Godoy, São Jose do Rio Preto, with a group of 46 women who had undergone surgery for the treatment of breast cancer. The following variables were evaluated: type and length of surgery; number of radiotherapy and chemotherapy sessions; continued feeling of the removed breast (phantom limb, infection, intensity of pain, and factors that improve and worsen the pain. The percentage of events was used for statistical analysis. About half the participants (52.1% performed modified radical surgery, with 91.3% removing only one breast; 82.6% of the participants did not perform breast reconstruction surgery. Insignificant pain was reported by 32.60% of the women and 67.3% said they suffered pain; it was mild in 28.8% of the cases (scale 1–5, moderate in 34.8% (scale 6–9, and severe in 4.3%. The main mechanisms used to cope with pain were painkillers in 41.30% of participants, rest in 21.73%, religious ceremonies in 17.39%, and chatting with friends in 8.69%. In conclusion, many mastectomized patients with lymphedema complain of pain, but pain is often underrecognized and undertreated.

  9. Seawater Immersion Aggravates Burn Injury Causing Severe Blood Coagulation Dysfunction

    Directory of Open Access Journals (Sweden)

    Hong Yan

    2016-01-01

    Full Text Available This study aimed to investigate the endothelial function in a canine model of burn injury combined with seawater immersion. The model of burn injury was established. The dogs were randomly divided into four groups including dogs with burn injury (B group, or burn injury combined with seawater immersion (BI group, or only immersion in seawater (I group, or control animals with no injury or immersion (C group. The circulating endothelial cell (CEC count and coagulation-fibrinolysis parameters were measured. The CEC count in B group increased at 4 h, 7 h, and 10 h after injury and then reduced, whereas it continuously increased to a greater extent in BI group (P<0.05. The von Willebrand factor (vWF activity, plasminogen activator inhibitor (PAI-1, and the ratio of thromboxane B2 (TXB2 to 6-keto-prostaglandin F1α (6-K-PGF1α in BI group had a marked increase after injury, and the tissue-type plasminogen activator (tPA in the BI group decreased. Microscope observations revealed thrombus formation in lungs of the animals in BI group, but not in C, I, or B groups. Burn injury causes endothelial dysfunction, and seawater immersion lastingly aggravates this injury, leading to a higher risk of developing thrombosis.

  10. Radiofrequency ablation of liver VX2 tumor: experimental results with MR diffusion-weighted imaging at 3.0T.

    Directory of Open Access Journals (Sweden)

    Yubao Liu

    Full Text Available To evaluate the value of DWI in detecting the lesions of pre- and post-radiofrequency ablation (RFA of the rabbit liver VX2 tumors.Twenty-two New Zealand White rabbits were tested. The protocol was approved by the Committee on the Ethics of Animal Experiments. Twenty separate tumor fragments were implanted into the livers of 20 rabbits, the liver was exposed by performing midline laparotomy. 3.0T MR DWI (b = 0, 200, 400, 600, 800,1000 s/mm2 were performed 14-21 days after tumor implantation (mean, 17 days in the 18 tumor-bearing animals. Then RFA was performed in the 18 tumor-bearing animals and in the two healthy animals. 3.0T MR DWI was performed 7-10 days after RFA (mean, 8 days. Pathology exam was performed immediately after the completion of post- RFA MR imaging. Analyzing the features of MRI and ADC values in the pre- and post- RFA lesions of the VX2 tumors, and histopathologic results were compared with imaging findings.The difference of ADC value between viable tumor and normal liver parenchyma was significant (P<.001. After RFA, when b = 200, 400, 600, 800, 1000 s/mm2, the differences of ADC values of viable tumor, granulation tissue, necrosis, normal liver parenchyma were significant (P<.001. At the time the animals were sacrificed after RFA and MR imaging, histopathologic results of local viable tumors were found in 9 (50% of the 18 treated tumors. Macroscopic viable tumors were found at the RFA sites in 3 (17%, all 3 macroscopic viable tumors were visualized at the periphery of the RFA areas.3.0T MR DWI can be used to follow up the progress of the RFA lesion, it is useful in detecting different tissues after RFA, and it is valuable in the further clinical research.

  11. Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient mice

    Directory of Open Access Journals (Sweden)

    Margarita Vida

    2015-07-01

    Full Text Available Interleukin-6 (IL-6 has emerged as an important mediator of fatty acid metabolism with paradoxical effects in the liver. Administration of IL-6 has been reported to confer protection against steatosis, but plasma and tissue IL-6 concentrations are elevated in chronic liver diseases, including fatty liver diseases associated with obesity and alcoholic ingestion. In this study, we further investigated the role of IL-6 on steatosis induced through a high-fat diet (HFD in wild-type (WT and IL-6-deficient (IL-6−/− mice. Additionally, HFD-fed IL-6−/− mice were also chronically treated with recombinant IL-6 (rIL-6. Obesity in WT mice fed a HFD associated with elevated serum IL-6 levels, fatty liver, upregulation of carnitine palmitoyltransferase 1 (CPT1 and signal transducer and activator of transcription-3 (STAT3, increased AMP kinase phosphorylation (p-AMPK, and downregulation of the hepatic lipogenic enzymes fatty acid synthase (FAS and stearoyl-CoA desaturase 1 (SCD1. The HFD-fed IL-6−/− mice showed severe steatosis, no changes in CPT1 levels or AMPK activity, no increase in STAT3 amounts, inactivated STAT3, and marked downregulation of the expression of acetyl-CoA carboxylase (ACCα/β, FAS and SCD1. The IL-6 chronic replacement in HFD-fed IL-6−/− mice restored hepatic STAT3 and AMPK activation but also increased the expression of the lipogenic enzymes ACCα/β, FAS and SCD1. Furthermore, rIL-6 administration was associated with aggravated steatosis and elevated fat content in the liver. We conclude that, in the context of HFD-induced obesity, the administration of rIL-6 might contribute to the aggravation of fatty liver disease through increasing lipogenesis.

  12. A study of standardized extracts of Picrorhiza kurroa Royle ex Benth in experimental nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Sapna N Shetty

    2010-01-01

    Full Text Available As a major organ of intermediary metabolism, the liver is exposed to a variety of metabolic insults due to diseases and xenobiotics viz., insulin resistance (IR drugs, toxins, microbial products, etc. One of the consequences of these metabolic insults including obesity and type 2 diabetes mellitus is the development of non-alcoholic fatty liver disease (NAFLD. The recent alarming increase in the prevalence of NAFLD compels the need to develop an appropriate animal model of the disease so as to evolve effective interventions. In this study, we have developed, in the rat, a new model of NAFLD showing several key features akin to the disease in humans. Male Wistar rats were challenged with 30% high fat diet (HFD - butter, for 2 weeks to induce NAFLD. A hydroalcoholic extract of Picrorhiza kurroa was administered to study the possible reversal of fatty changes in the liver. The extract was given in two doses viz., 200mg/kg and 400 mg/kg b.i.d., p.o. for a period of 4 weeks. There were three control groups (n = 6/group - vehicle with a regular diet, vehicle with HFD, and HFD with silymarin - a known hepatoprotective. Histopathology showed that the P. kurroa extract brought about a reversal of the fatty infiltration of the liver (mg/g and a lowering of the quantity of hepatic lipids (mg/g compared to that in the HFD control group (38.33 ± 5.35 for 200mg/kg; 29.44 ± 8.49 for 400mg/kg of P. kurroa vs.130.07 ± 6.36mg/g of liver tissue in the HFD control group; P<0.001. Compared to the standard dose of the known hepatoprotective silymarin, P. kurroa reduced the lipid content (mg/g of the liver more significantly at the dose of 400mg/kg (57.71 ± 12.45mg/kg vs. 29.44 ± 8.49 for the silymarin group vs. 400mg/kg of P. kurroa, P<0.001. In view of the increasing prevalence of metabolic syndrome and NAFLD, P. kurroa should be investigated by the reverse pharmacology path as a potential drug for the treatment of NAFLD, and essential safety studies and

  13. Tolbutamide attenuates diazoxide-induced aggravation of hypoxic cell injury.

    Science.gov (United States)

    Pissarek, M; Reichelt, C; Krauss, G J; Illes, P

    1998-11-23

    ATP-dependent potassium (KATP) channels of neurons are closed in the presence of physiological levels of intracellular ATP and open when ATP is depleted during hypoxia or metabolic damage. The present study investigates hypoxic alterations of purine and pyrimidine nucleotide levels supposed to intracellularly modulate KATP channels. In addition, the effects of the KATP channel activator diazoxide and its antagonist tolbutamide were investigated on ATP, GTP, CTP and UTP levels in slices of the parietal cortex. Hypoxia was evoked by saturation of the medium with 95% N2-5% CO2 instead of 95% O2-5% CO2 for 5 min. Nucleotide contents were measured by anion-exchange HPLC in neutralized perchloric acid extracts obtained from slices frozen immediately at the end of incubation. Hypoxia per se decreased purine and pyrimidine nucleoside triphosphate contents. Thus, ATP and GTP contents were reduced to 69.9 and 77.6% of the respective normoxic levels. UTP and CTP contents were even more decreased (to 60.9 and 41.6%),, probably because the salvage pathway of these pyrimidine nucleotides is less effective than that of the purine nucleotides ATP and GTP. While tolbutamide (30 microM) had no effect on the hypoxia-induced decrease of nucleotides, diazoxide at 300, but not 30 microM aggravated the decline of ATP, UTP and CTP to 51.8, 37.5 and 28.5% of the contents observed at normoxia; GTP levels also showed a tendency to decrease after diazoxide application. Tolbutamide (300 microM) antagonized the effects of diazoxide (300 but not 30 microM aggravated the decline of ATP, UTP and CTP to 51.8, 37.5 and 28.5% of the contents observed at normoxia; GTP levels also showed a tendency to decrease after diazoxide application. Tolbutamide (300 microM) antagonized the effects of diazoxide (300 MicroM). Nucleoside diphosphate (ADP, GDP and UDP) levels were uniformly increased by hypoxia. There was no hypoxia-induced increase of ADP contents in the presence of tolbutamide (300 microM). The ATP

  14. Puerarin ameliorates experimental alcoholic liver injury by inhibition of endotoxin gut leakage, Kupffer cell activation, and endotoxin receptors expression.

    Science.gov (United States)

    Peng, Jing-Hua; Cui, Tuan; Huang, Fu; Chen, Liang; Zhao, Yu; Xu, Lin; Xu, Li-Li; Feng, Qin; Hu, Yi-Yang

    2013-03-01

    Puerarin, an isoflavone component extracted from Kudzu (Pueraria lobata), has been demonstrated to alleviate alcohol-related disorders. Our study examined whether puerarin ameliorates chronic alcoholic liver injury through inhibition of endotoxin gut leakage, the subsequent Kupffer cell activation, and endotoxin receptors expression. Rats were provided with the Liber-DeCarli liquid diet for 8 weeks. Puerarin (90 mg/kg or 180 mg/kg daily) was orally administered from the beginning of the third week until the end of the experiment. Chronic alcohol intake caused increased serum alanine aminotransferase, aspartate aminotransferase, hepatic gamma-glutamyl transpeptidase, and triglyceride levels as well as fatty liver and neutrophil infiltration in hepatic lobules as determined by biochemical and histologic assays. A significant increase of liver tumor necrosis factor α was detected by enzyme-linked immunosorbent assay. These pathologic effects correlated with increased endotoxin level in portal vein and upregulated protein expression of hepatic CD68, lipopolysaccharide-binding protein, CD14, Toll-like receptor 2, and Toll-like receptor 4. Meanwhile, the intestinal microvilli were observed to be sparse, shortened, and irregularity in distribution under the transmission electron microscope in conjunction with the downregulated intestinal zonula occludens-1 protein expression. These hepatic pathologic changes were significantly inhibited in puerarin-treated animals as were the endotoxin levels and hepatic CD68 and endotoxin receptors. Moreover, the pathologic changes in intestinal microvillus and the decreased intestinal zonula occludens-1 were also ameliorated with puerarin treatment. These results thus demonstrate that puerarin inhibition of endotoxin gut leakage, Kupffer cell activation, and endotoxin receptors expression is involved in the alleviation of chronic alcoholic liver injury in rats.

  15. Dietary hypercholesterolemia aggravates contrast media-induced nephropathy

    Institute of Scientific and Technical Information of China (English)

    杨定位; 贾汝汉; 杨定平; 丁国华; 黄从新

    2004-01-01

    Background Contrast media administration can result in severe nephrotoxicity under pathological conditions such as diabetic nephropathy, congestive heart failure, dehydration, et al. The purpose of this study was to evaluate the effects of dietary hypercholesterolemia on contrast media-induced changes in renal function, blood flow, and histopathology.Methods Rats were fed either on a normal rodent diet (group N) or a high-cholesterol supplemented diet (group H; 4% cholesterol and 1% cholic acid) for 8 weeks. Half of the animals (n =6) from each diet group were then given a tail vein injection of 60% diatrizoate (6 ml/kg; group NC and group HC)and the other half were administered saline. Total serum cholesterol, triglyceride, serum creatinine,creatinine clearance rate, fractional excretion of sodium and potassium, and cortical nitric oxide production were determined one day following contrast media administration. Renal blood flow was determined by color Doppler flow imaging and pulsed-mode Doppler. Renal histopathology was observed by light microscopy.Results Total serum cholesterol and resistance indices of renal blood vessels increased significantly,while creatinine clearance rate and production of nitric oxide in the renal cortex decreased markedly in group HC and group H when compared to group N and group NC. The creatinine clearance rate decreased significantly in group HC compared to group H. Serum creatinine levels and fractional excretion of sodium and potassium in group HC were significantly higher than those in the other three groups. Severe tubular degeneration and necrosis, protein cast accumulation, and medullary congestion were found in group HC.Conclusion Hypercholesterolemia is a risk factor for contrast media-induced nephropathy.Hypercholesterolemia aggravates contrast media-induced nephrotoxicity through the reduced production of nitric oxide.

  16. Aryl Hydrocarbon Receptor Activation by TCDD Modulates Expression of Extracellular Matrix Remodeling Genes during Experimental Liver Fibrosis

    Science.gov (United States)

    Lamb, Cheri L.; Cholico, Giovan N.; Perkins, Daniel E.; Fewkes, Michael T.; Oxford, Julia Thom; Lujan, Trevor J.; Morrill, Erica E.

    2016-01-01

    The aryl hydrocarbon receptor (AhR) is a soluble, ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Increasing evidence implicates the AhR in regulating extracellular matrix (ECM) homeostasis. We recently reported that TCDD increased necroinflammation and myofibroblast activation during liver injury elicited by carbon tetrachloride (CCl4). However, TCDD did not increase collagen deposition or exacerbate fibrosis in CCl4-treated mice, which raises the possibility that TCDD may enhance ECM turnover. The goal of this study was to determine how TCDD impacts ECM remodeling gene expression in the liver. Male C57BL/6 mice were treated for 8 weeks with 0.5 mL/kg CCl4, and TCDD (20 μg/kg) was administered during the last two weeks. Results indicate that TCDD increased mRNA levels of procollagen types I, III, IV, and VI and the collagen processing molecules HSP47 and lysyl oxidase. TCDD also increased gelatinase activity and mRNA levels of matrix metalloproteinase- (MMP-) 3, MMP-8, MMP-9, and MMP-13. Furthermore, TCDD modulated expression of genes in the plasminogen activator/plasmin system, which regulates MMP activation, and it also increased TIMP1 gene expression. These findings support the notion that AhR activation by TCDD dysregulates ECM remodeling gene expression and may facilitate ECM metabolism despite increased liver injury. PMID:27672655

  17. Effect of N-Feruloylserotonin and Methotrexate on Severity of Experimental Arthritis and on Messenger RNA Expression of Key Proinflammatory Markers in Liver

    Directory of Open Access Journals (Sweden)

    Ľudmila Pašková

    2016-01-01

    Full Text Available Rheumatoid arthritis (RA is a chronic inflammatory disease, leading to progressive destruction of joints and extra-articular tissues, including organs such as liver and spleen. The purpose of this study was to compare the effects of a potential immunomodulator, natural polyphenol N-feruloylserotonin (N-f-5HT, with methotrexate (MTX, the standard in RA therapy, in the chronic phase of adjuvant-induced arthritis (AA in male Lewis rats. The experiment included healthy controls (CO, arthritic animals (AA, AA given N-f-5HT (AA-N-f-5HT, and AA given MTX (AA-MTX. N-f-5HT did not affect the body weight change and clinical parameters until the 14th experimental day. Its positive effect was rising during the 28-day experiment, indicating a delayed onset of N-f-5HT action. Administration of either N-f-5HT or MTX caused reduction of inflammation measured as the level of CRP in plasma and the activity of LOX in the liver. mRNA transcription of TNF-α and iNOS in the liver was significantly attenuated in both MTX and N-f-5HT treated groups of arthritic rats. Interestingly, in contrast to MTX, N-f-5HT significantly lowered the level of IL-1β in plasma and IL-1β mRNA expression in the liver and spleen of arthritic rats. This speaks for future investigations of N-f-5HT as an agent in the treatment of RA in combination therapy with MTX.

  18. Imprecise methods may both obscure and aggravate a relation between fat and breast cancer

    DEFF Research Database (Denmark)

    Heitmann, B L; Frederiksen, Peder

    2007-01-01

    Bias in diet reporting may be both random and non-random, and may be found with simpler as well as more advanced dietary instruments. A random bias will contribute to obscure relations between diet and disease. A systematic bias may obscure or aggravate such associations. Underreporting of non......-protein energy has been found to be substantial, particularly among those who are obese or have high dietary intakes. Such a non-random bias on the group level would tend to aggravate associations between dietary non-protein and disease. Whether the net result of the random and non-random bias aggravates...

  19. Hepatocyte nuclear factor 4α suppresses the aggravation of colon carcinoma.

    Science.gov (United States)

    Yao, Hou Shan; Wang, Juan; Zhang, Xiao Ping; Wang, Liang Zhe; Wang, Yi; Li, Xin Xing; Jin, Kai Zhou; Hu, Zhi Qian; Wang, Wei Jun

    2016-05-01

    Hepatocyte nuclear factor 4-α (HNF4α), a nuclear receptor, is expressed at lower levels in colon carcinoma tissues than in adjacent normal tissues. However, the relation between HNF4α and colon cancer progression and the underlying molecular mechanisms remain unclear. Here, we investigated the role of HNF4α in the progression of colon carcinoma. We showed that HNF4α mRNA and protein were downregulated in colon carcinoma specimens. HNF4α expression was related to pT classification (P colon carcinoma patients. Patients with low or negative HNF4α expression had worse 3-year progression-free survival (PFS, P = 0.006) and overall survival (OS, P = 0.005) than patients with high HNF4α expression. Low HNF4α expression was an independent prognostic factor for 3-year PFS (hazard ratio 2.94; 95% confidence interval 1.047-8.250; P = 0.041). Ectopic expression of HNF4α inhibited colon carcinoma cell (HT29, LoVo, and SW480) proliferation, migration, and invasion, induced G2/M phase arrest and promoted apoptosis. Ectopic expression of HNF4α upregulated E-cadherin and downregulated vimentin in vitro, and suppressed SW480 xenograft tumor growth and liver metastasis in vivo. Furthermore, HNF4α overexpression downregulated the expression of snail, slug and twist. HNF4α inhibited EMT through its effect on the Wnt/β-catenin signaling pathway, and HNF4α downregulation may be mediated by promoter methylation in cancer tissues. Our results suggest that downregulation of HNF4α plays a critical role in the aggravation of colon carcinoma possibly by promoting EMT via the Wnt/β-catenin signaling pathway and by affecting apoptosis and cell cycle progression.

  20. Aggravation of excessive daytime sleepiness concurrent with aggravation of an injured ascending reticular activating system in a patient with mild traumatic brain injury

    Science.gov (United States)

    Jang, Sung Ho; Kwon, Hyeok Gyu

    2017-01-01

    Abstract Background: We report on a patient who developed aggravation of excessive daytime sleepiness (EDS) concurrent with aggravation of an injured ascending reticular activating system (ARAS) following mild traumatic brain injury (TBI), demonstrated by follow-up diffusion tensor tractographies (DTTs). Methods: A 42-year-old male patient experienced head trauma resulting from flexion-hyperextension injury after collision with another vehicle from behind while stopped at an intersection. The patient lost consciousness for approximately 10 seconds and experienced no post-traumatic amnesia following the accident. The patient's Glasgow Coma Scale score was 15. No specific lesion was observed on the conventional brain MRI performed at 10 weeks after onset. The patient complained of EDS after the head trauma and aggravation of EDS with passage of time. The Epworth Sleepiness Scale indicated abnormality with a score of 12 at 10 weeks after onset (cut-off: 10 points full mark: 24 score) and it was aggravated with a score of 18 at 16 months. Results: On 10-week DTT, decreased neural connectivity of the intralaminar thalamic nucleus to the prefrontal cortex and basal forebrain was observed in both hemispheres. However, no significant abnormality was observed in the dorsal and ventral lower ARAS. On 16-month DTT, the upper portion of the left dorsal lower ARAS showed partial tearing and the ventral lower ARAS showed thinning (both sides) and partial tearing (right side). Conclusions: Aggravation of EDS concurrent with aggravation of an injured ARAS was demonstrated in a patient with mild TBI using DTT. PMID:28121943

  1. Protective effect of glycine on liver injury during liver transplantation

    Institute of Scientific and Technical Information of China (English)

    WANG Yao-sheng; YAN Ye-hong; ZOU Xun-feng

    2010-01-01

    @@ Multiple procedures of liver transplantation bring conditions producing cold ischemia-reperfusion (I/R) injury. During cold storage, the graft organ is subjected to cold ischemia, also known as hypoxia injury. After reperfusion, although hypoxic condition has been ameliorated, reoxygenation of the graft liver can produce not only reperfusion injury including generation of oxygen free radical, lipoperoxidation and calcium overload, but also aggravate the hypoxia damage, involving endothelial cell (EC) damage, Kupffer cell (KC) activation, and adherence of neutrophils and platelets to Ecs. Clinically, I/R injury is one of the major problems complicating liver transplantation, and can ultimately result in serious complications such as primary nonfunction and delayed graft function, which may lead to the need of urgent retransplantation. Therefore, the therapeutic strategies of attenuating graft I/R injury are clinically significant and might improve overall graft function and survival.

  2. Metallothionein deficiency aggravates depleted uranium-induced nephrotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Yuhui; Huang, Jiawei; Gu, Ying; Liu, Cong; Li, Hong; Liu, Jing; Ren, Jiong; Yang, Zhangyou [State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, No. 30 Gaotanyan Street, Shapingba District, Chongqing 400038 (China); Peng, Shuangqing [Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Science, 20 Dongdajie Street, Fengtai District, Beijing 100071 (China); Wang, Weidong, E-mail: wwdwyl@sina.com [Department of Radiation Oncology, Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Shanghai 200233 (China); Li, Rong, E-mail: yuhui_hao@126.com [State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, No. 30 Gaotanyan Street, Shapingba District, Chongqing 400038 (China)

    2015-09-15

    Depleted uranium (DU) has been widely used in both civilian and military activities, and the kidney is the main target organ of DU during acute high-dose exposures. In this study, the nephrotoxicity caused by DU in metallothionein-1/2-null mice (MT −/−) and corresponding wild-type (MT +/+) mice was investigated to determine any associations with MT. Each MT −/− or MT +/+ mouse was pretreated with a single dose of DU (10 mg/kg, intraperitoneal injection) or an equivalent volume of saline. After 4 days of DU administration, kidney changes were assessed. After DU exposure, serum creatinine and serum urea nitrogen in MT −/− mice significantly increased than in MT +/+ mice, with more severe kidney pathological damage. Moreover, catalase and superoxide dismutase (SOD) decreased, and generation of reactive oxygen species and malondialdehyde increased in MT −/− mice. The apoptosis rate in MT −/− mice significantly increased, with a significant increase in both Bax and caspase 3 and a decrease in Bcl-2. Furthermore, sodium-glucose cotransporter (SGLT) and sodium-phosphate cotransporter (NaPi-II) were significantly reduced after DU exposure, and the change of SGLT was more evident in MT −/− mice. Finally, exogenous MT was used to evaluate the correlation between kidney changes induced by DU and MT doses in MT −/− mice. The results showed that, the pathological damage and cell apoptosis decreased, and SOD and SGLT levels increased with increasing dose of MT. In conclusion, MT deficiency aggravated DU-induced nephrotoxicity, and the molecular mechanisms appeared to be related to the increased oxidative stress and apoptosis, and decreased SGLT expression. - Highlights: • MT −/− and MT +/+ mice were used to evaluate nephrotoxicity of DU. • Renal damage was more evident in the MT −/− mice after exposure to DU. • Exogenous MT also protects against DU-induced nephrotoxicity. • MT deficiency induced more ROS and apoptosis after exposure to

  3. Experimental chronic copper toxicity in sheep: histological and histochemical changes during the development of the lesions in the liver

    Energy Technology Data Exchange (ETDEWEB)

    Ishmael, J.; Gopinath, C.; Howell, J.McC.

    1971-01-01

    Histological and histochemical changes in the livers of 8 sheep given continuous doses of copper sulfate were studied in serial samples obtained by needle biopsy. Necrosis of isolated parenchymal cells and occasional swollen P.A.S.-positive, diastase-resistant, copper containing Kupffer cells, which were rich in acid phosphatase, were seen in biopsies taken some 6 weeks before the haemolytic crisis. In subsequent biopsies isolated parenchymal cell necrosis became more widespread, swollen Kupffer cells were more numerous and tended to occur in clusters. Many parenchymal cells appeared swollen and showed fatty change, karyomegaly and nuclear vacuolation. In biopsies taken at the time of the haemolytic crisis extensive focal necrosis of liver tissue was seen. In animals which had survived a haemolytic episode large amounts of bile pigment were present in canaliculi and small bile ducts, and periportal fibrosis occurred. The reduction in activity of the hydrolytic enzymes adenosine triphosphatase and non-specific esterase and of the oxidative enzymes succinic dehydrogenase and glutamic dehydrogenase seen in the first post-dosing biopsies became progressively more severe. Gross and microscopic lesions found at post-mortem examination are described and attention is drawn to the status spongiosus in the white matter of the central nervous system.

  4. Prostacyclin inhibition by indomethacin aggravates hepatic damage and encephalopathy in rats with thioacetamide-induced fulminant hepatic failure

    Institute of Scientific and Technical Information of China (English)

    Chi-Jen Chu; Shou-Dong Lee; Ching-Chin Hsiao; Teh-Fang Wang; Cho-Yu Chan; Fa-Yauh Lee; Full-Young Chang; Yi-Chou Chen; Hui-Chun Huang; Sun-Sang Wang

    2005-01-01

    AIM: Vasodilatation and increased capillary permeability have been proposed to be involved in the pathogenesis of acute and chronic form of hepatic encephalopathy.Prostacyclin (PGI2) and nitric oxide (NO) are important contributors to hyperdynamic circulation in portal hypertensive states. Our previous study showed that chronic inhibition of NO had detrimental effects on the severity of encephalopathy in thioacetamide (TAA)-treated rats due to aggravation of liver damage. To date, there are no detailed data concerning the effects of PGI2 inhibition on the severity of hepatic encephalopathy during fulminant hepatic failure.METHODS: Male Sprague-Dawley rats weighing 300-350 g were used. Fulminant hepatic failure was induced by were divided into two groups to receive intraperitoneal saline (N/S, n = 20) for 5 d, starting 2 d before TAA administration. Severity of encephalopathy was assessed by the counts of motor activity measured with Opto-Varimex animal activity meter. Plasma tumor necrosis factor-α(TNF-α, an index of liver injury) and 6-keto-PGF1α (a metabolite of PGI2) levels were measured by enzyme-linked immunosorbent assay.RESULTS: As compared with N/S-treated rats, the mortality rate was significantly higher in rats receiving indomethacin (20% vs5%, P<0.01). Inhibition of PGI2 created detrimental effects on total movement counts (indomethacin vs N/S:438±102 vs841±145 counts/30 min, P<0.05). Rats treated with indomethacin had significant higher plasma levels of TNF-α (indomethacin vsN/S: 22±5 vs 10±1 pg/mL, P<0.05)and lower plasma levels of 6-keto-PGF1α (P<0.001), but not total bilirubin or creatinine (P>0.05), as compared with rats treated with N/S.CONCLUSION: Chronic indomethacin administration has detrimental effects on the severity of encephalopathy in TAA-treated rats and this phenomenon may be attributed to the aggravation of liver injury. This study suggests that PGI2 may provide a protective role in the development of fulminant

  5. Liver Transplant

    Science.gov (United States)

    ... Baby Boomers Get Tested Core Programs HE Webinar Disney 2014 5 Ways to Love Your Liver Liver ... Drive Away Liver Disease Liver Lowdown Aug 2013 Disney Marathon In The Field Healthy Foods Diet Recommendations ...

  6. Feed exposure to FB1 can aggravate pneumonic damages in pigs provoked by P. multocida.

    Science.gov (United States)

    Kovács, Melinda; Pósa, Roland; Tuboly, Tamás; Donkó, Tamás; Repa, Imre; Tossenberger, János; Szabó-Fodor, Judit; Stoev, Stoycho; Magyar, Tibor

    2016-10-01

    The possible interaction between Pasteurella multocida and the mycotoxin fumonisin B1 (FB1), recognised as one of the most often food/feed contaminant, was studied with the aim to evaluate whether and how FB1 can influence and/or complicate the development and severity of various pathological damages provoked by Pasteurella multocida in some internal organs of pigs. Heavier lung pathology was seen in pigs experimentally infected with Pasteurella multocida, when the same were exposed to 20ppm dietary levels of fumonisin B1 (FB1) as was assessed by gross pathology, pathomorphological examinations, clinical biochemistry and some immunological investigations. The most typical damages in FB1 treated pigs were the strong oedema in the lung and the slight oedema in the other internal organs and mild degenerative changes in the kidneys, whereas the typical pathomorphological findings in pigs infected with Pasteurella multocida was broncho-interstitial pneumonia. FB1 was found to aggravate pneumonic changes provoked by P. multocida in the cranial lobes of the lung and to complicate pneumonic damages with interstitial oedema in the lung. No macroscopic damages were observed in the pigs infected only with Pasteurella multocida. It can be concluded that the feed intake of FB1 in pigs may complicate or exacerbate the course of P. multocida serotype A infection.

  7. Ocean acidification may aggravate social-ecological trade-offs in coastal fisheries.

    Directory of Open Access Journals (Sweden)

    Rudi Voss

    Full Text Available Ocean Acidification (OA will influence marine ecosystems by changing species abundance and composition. Major effects are described for calcifying organisms, which are significantly impacted by decreasing pH values. Direct effects on commercially important fish are less well studied. The early life stages of fish populations often lack internal regulatory mechanisms to withstand the effects of abnormal pH. Negative effects can be expected on growth, survival, and recruitment success. Here we study Norwegian coastal cod, one of the few stocks where such a negative effect was experimentally quantified, and develop a framework for coupling experimental data on OA effects to ecological-economic fisheries models. In this paper, we scale the observed physiological responses to the population level by using the experimentally determined mortality rates as part of the stock-recruitment relationship. We then use an ecological-economic optimization model, to explore the potential effect of rising CO2 concentration on ecological (stock size, economic (profits, consumer-related (harvest and social (employment indicators, with scenarios ranging from present day conditions up to extreme acidification. Under the assumptions of our model, yields and profits could largely be maintained under moderate OA by adapting future fishing mortality (and related effort to changes owing to altered pH. This adaptation comes at the costs of reduced stock size and employment, however. Explicitly visualizing these ecological, economic and social tradeoffs will help in defining realistic future objectives. Our results can be generalized to any stressor (or stressor combination, which is decreasing recruitment success. The main findings of an aggravation of trade-offs will remain valid. This seems to be of special relevance for coastal stocks with limited options for migration to avoid unfavorable future conditions and subsequently for coastal fisheries, which are often small

  8. Ocean acidification may aggravate social-ecological trade-offs in coastal fisheries.

    Science.gov (United States)

    Voss, Rudi; Quaas, Martin F; Schmidt, Jörn O; Kapaun, Ute

    2015-01-01

    Ocean Acidification (OA) will influence marine ecosystems by changing species abundance and composition. Major effects are described for calcifying organisms, which are significantly impacted by decreasing pH values. Direct effects on commercially important fish are less well studied. The early life stages of fish populations often lack internal regulatory mechanisms to withstand the effects of abnormal pH. Negative effects can be expected on growth, survival, and recruitment success. Here we study Norwegian coastal cod, one of the few stocks where such a negative effect was experimentally quantified, and develop a framework for coupling experimental data on OA effects to ecological-economic fisheries models. In this paper, we scale the observed physiological responses to the population level by using the experimentally determined mortality rates as part of the stock-recruitment relationship. We then use an ecological-economic optimization model, to explore the potential effect of rising CO2 concentration on ecological (stock size), economic (profits), consumer-related (harvest) and social (employment) indicators, with scenarios ranging from present day conditions up to extreme acidification. Under the assumptions of our model, yields and profits could largely be maintained under moderate OA by adapting future fishing mortality (and related effort) to changes owing to altered pH. This adaptation comes at the costs of reduced stock size and employment, however. Explicitly visualizing these ecological, economic and social tradeoffs will help in defining realistic future objectives. Our results can be generalized to any stressor (or stressor combination), which is decreasing recruitment success. The main findings of an aggravation of trade-offs will remain valid. This seems to be of special relevance for coastal stocks with limited options for migration to avoid unfavorable future conditions and subsequently for coastal fisheries, which are often small scale local

  9. A case of huge primary liposarcoma in the liver

    Institute of Scientific and Technical Information of China (English)

    Liang-Mou Kuo; Hong-Shiue Chou; Kun-Ming Chan; Ming-Chin Yu; Wei-Chen Lee

    2006-01-01

    Primary liver liposarcoma is a rare disease. Because of its rarity, the knowledge of the clinical course, management, and prognosis of primary liver liposarcoma are all limited for clinicians. A 61-year-old female patient who suffered from a huge primary liposarcoma in the central portion of the liver had the clinical presentations of fever, nausea, vomiting, jaundice, and body weight loss.The huge tumor was resected successfully. However,the tumor recurred repeatedly and she had repeated hepatectomies to remove the tumor. Thetumor became aggravating after repeated surgeries. Eventually, the patient had cervical spinal metastasis of liposarcoma and she survived for 26 months after liver liposarcoma was diagnosed. Although the tumor may become aggravating after repeated surgeries, repeated hepatectomies are still the best policy to achieve a long-term survival for the patients.

  10. NLRP3 inflammasome as a target of berberine in experimental murine liver injury: interference with P2X7 signalling.

    Science.gov (United States)

    Vivoli, Elisa; Cappon, Andrea; Milani, Stefano; Piombanti, Benedetta; Provenzano, Angela; Novo, Erica; Masi, Alessio; Navari, Nadia; Narducci, Roberto; Mannaioni, Guido; Moneti, Gloriano; Oliveira, Claudia P; Parola, Maurizio; Marra, Fabio

    2016-10-01

    Berberine (BRB) is commonly used in herbal medicine, but its mechanisms of action are poorly understood. In the present study, we tested BRB in steatohepatitis induced by a methionine- and choline-deficient (MCD) diet, in acute acetaminophen intoxication and in cultured murine macrophages. BRB markedly improved parameters of liver injury and necroinflammation induced by the MCD diet, although increased mortality was observed by mechanisms independent of bacterial infections or plasma levels of BRB. The MCD diet induced up-regulation of all components of the NLRP3 (NACHT, LRR and PYD domain-containing protein 3) inflammasome, and increased hepatic levels of mature IL-1β (interleukin 1β). All of these parameters were significantly reduced in mice treated with BRB. In mice administered an acetaminophen overdose, a model dependent on inflammasome activation, BRB reduced mortality and ALT (alanine aminotransferase) elevation, and limited the expression of inflammasome components. In vitro, LPS (lipopolysaccharide)-induced activation of NLRP3 inflammasome in RAW264.7 murine macrophages was markedly decreased by pre-incubation with BRB. BRB significantly limited the activation of the purinergic receptor P2X7, involved in the late phases of inflammasome activation. Upon P2X7 knockdown, the ability of BRB to block LPS-induced secretion of IL-1β was lost. These data indicate that administration of BRB ameliorates inflammation and injury in two unrelated murine models of liver damage. We demonstrate for the first time that BRB interferes with activation of the NLRP3 inflammasome pathway in vivo and in vitro, through a mechanism based on interference with activation of P2X7, a purinergic receptor involved in inflammasome activation.

  11. Combined 'en bloc' liver and pancreas transplantation in patients with liver disease and type 1 diabetes mellitus.

    Science.gov (United States)

    Pirenne, Jacques; Deloose, Koen; Coosemans, Willy; Aerts, Raymond; Van Gelder, Frank; Kuypers, Dirk; Maes, Bart; Verslype, Chris; Yap, Paul; Van Steenbergen, Werner; Roskams, Tania; Mathieu, Chantal; Fevery, Johan; Nevens, Frederik

    2004-11-01

    Liver disease alters the glucose metabolism and may cause diabetes, but this condition is potentially reversible with liver transplantation (LTx). Type 1 diabetes mellitus may be coincidentally present in a LTx candidate and immunosuppressive drugs will aggravate diabetes and make its management more difficult for posttransplant. In addition, diabetes negatively influences outcome after LTx. Therefore, the question arises as to why not transplanting the pancreas in addition to the liver in selected patients suffering from both liver disease and Type 1 diabetes. We report two cases of en bloc combined liver and pancreatic transplantation, a technique originally described a decade ago in the treatment of upper abdominal malignancies but rarely used for the treatment of combined liver disease and Type 1 diabetes. Both recipients are currently liver disease-free and insulin-free more than 2 and 4 years posttransplant, respectively. Surgical, medical and immunological aspects of combined liver-pancreas transplantation are discussed in the light of the existing relevant literature.

  12. Investigation of the causes of clinical symptom aggravation in process of intravenous thrombolysis with alteplase

    Directory of Open Access Journals (Sweden)

    LI Chen-hua

    2013-04-01

    Full Text Available Objective To explore the causes of aggravation of microcirculation disorders in the process of intravenous thrombolysis with alteplase and the clinical outcomes. Methods The clinical data of the aggravated signs and symptoms of 13 cases treated by alteplase were reported, and the onset characteristics and clinical outcomes were analysed to summarize emergency experiences. Results There were 13 patients with stenosis of intracranial large arteries occurred perforating branch infarctions caused by the blocking of carried arteries (8 cases in internal carotid system, 5 cases in vertebral-basilar system. In the process of thrombolytic therapy, main aggravated presentations including cortical ischemic symptom, quadriplegia, exacerbated disturbance of consciousness were seen. Imaging examinations showed multiple new petechial ischemic foci in cortex and watershed region or increasing of infarct foci in cerebellum and brain stem. The prognosis was favorable after expectant treatment. NIHSS score was 8.69 ± 3.42 at 24 h after treatment, and mRS score was 0.94 ±0.37 at 3 month-follow-up. Neurologic deficit and quality of life were evidently improved. Conclusion In the course of intravenous thrombolytic therapy with alteplase. Aggravated clinical signs and symptoms may be related to various factors. Emboli disintegration inducing microcirculation disorder is inferred to be the main cause. For patients presenting aggravated signs and symptoms in thrombolysis process, favorable outcomes may occur as long as intensive care and timely treatment are performed.

  13. Cysteinyl leukotriene signaling aggravates myocardial hypoxia in experimental atherosclerotic heart disease

    DEFF Research Database (Denmark)

    Nobili, Elena; Salvado, M Dolores; Folkersen, Lasse Westergaard;

    2012-01-01

    Cysteinyl-leukotrienes (cys-LT) are powerful spasmogenic and immune modulating lipid mediators involved in inflammatory diseases, in particular asthma. Here, we investigated whether cys-LT signaling, in the context of atherosclerotic heart disease, compromises the myocardial microcirculation and ...

  14. Intrinsic renal cell and leukocyte-derived TLR4 aggravate experimental anti-MPO glomerulonephritis

    NARCIS (Netherlands)

    Summers, Shaun A.; van der Veen, Betty S.; O'Sullivan, Kim M.; Gan, Poh-Yi; Ooi, Joshua D.; Heeringa, Peter; Satchell, Simon C.; Mathieson, Peter W.; Saleem, Moin A.; Visvanathan, Kumar; Holdsworth, Stephen R.; Kitching, A. Richard

    2010-01-01

    Antimyeloperoxidase antibodies can cause crescentic glomerulonephritis and pulmonary hemorrhage. Toll-like receptors (TLRs) respond to infectious agents activating host defenses, whereas infections potentially initiate disease and provoke relapses. Neutrophils were found to be key effector cells of

  15. Cysteinyl leukotriene signaling aggravates myocardial hypoxia in experimental atherosclerotic heart disease.

    Directory of Open Access Journals (Sweden)

    Elena Nobili

    Full Text Available BACKGROUND: Cysteinyl-leukotrienes (cys-LT are powerful spasmogenic and immune modulating lipid mediators involved in inflammatory diseases, in particular asthma. Here, we investigated whether cys-LT signaling, in the context of atherosclerotic heart disease, compromises the myocardial microcirculation and its response to hypoxic stress. To this end, we examined Apoe(-/- mice fed a hypercholesterolemic diet and analysed the expression of key enzymes of the cys-LT pathway and their receptors (CysLT1/CysLT2 in normal and hypoxic myocardium as well as the potential contribution of cys-LT signaling to the acute myocardial response to hypoxia. METHODS AND PRINCIPAL FINDINGS: Myocardial biopsies from Apoe(-/- mice demonstrated signs of chronic inflammation with fibrosis, increased apoptosis and expression of IL-6, as compared to biopsies from C57BL/6J control mice. In addition, we found increased leukotriene C(4 synthase (LTC(4S and CysLT1 expression in the myocardium of Apoe(-/- mice. Acute bouts of hypoxia further induced LTC(4S expression, increased LTC(4S enzyme activity and CysLT1 expression, and were associated with increased extension of hypoxic areas within the myocardium. Inhibition of cys-LT signaling by treatment with montelukast, a selective CysLT1 receptor antagonist, during acute bouts of hypoxic stress reduced myocardial hypoxic areas in Apoe(-/- mice to levels equal to those observed under normoxic conditions. In human heart biopsies from 14 patients with chronic coronary artery disease mRNA expression levels of LTC(4S and CysLT1 were increased in chronic ischemic compared to non-ischemic myocardium, constituting a molecular basis for increased cys-LT signaling. CONCLUSION: Our results suggest that CysLT1 antagonists may have protective effects on the hypoxic heart, and improve the oxygen supply to areas of myocardial ischemia, for instance during episodes of sleep apnea.

  16. Intermittent hypoxia can aggravate motor neuronal loss and cognitive dysfunction in ALS mice.

    Directory of Open Access Journals (Sweden)

    Sung-Min Kim

    Full Text Available BACKGROUND: Patients with ALS may be exposed to variable degrees of chronic intermittent hypoxia. However, all previous experimental studies on the effects of hypoxia in ALS have only used a sustained hypoxia model and it is possible that chronic intermittent hypoxia exerts effects via a different molecular mechanism from that of sustained hypoxia. No study has yet shown that hypoxia (either chronic intermittent or sustained can affect the loss of motor neurons or cognitive function in an in vivo model of ALS. OBJECTIVE: To evaluate the effects of chronic intermittent hypoxia on motor and cognitive function in ALS mice. METHODS: Sixteen ALS mice and 16 wild-type mice were divided into 2 groups and subjected to either chronic intermittent hypoxia or normoxia for 2 weeks. The effects of chronic intermittent hypoxia on ALS mice were evaluated using the rotarod, Y-maze, and wire-hanging tests. In addition, numbers of motor neurons in the ventral horn of the spinal cord were counted and western blot analyses were performed for markers of oxidative stress and inflammatory pathway activation. RESULTS: Compared to ALS mice kept in normoxic conditions, ALS mice that experienced chronic intermittent hypoxia had poorer motor learning on the rotarod test, poorer spatial memory on the Y-maze test, shorter wire hanging time, and fewer motor neurons in the ventral spinal cord. Compared to ALS-normoxic and wild-type mice, ALS mice that experienced chronic intermittent hypoxia had higher levels of oxidative stress and inflammation. CONCLUSIONS: Chronic intermittent hypoxia can aggravate motor neuronal death, neuromuscular weakness, and probably cognitive dysfunction in ALS mice. The generation of oxidative stress with activation of inflammatory pathways may be associated with this mechanism. Our study will provide insight into the association of hypoxia with disease progression, and in turn, the rationale for an early non-invasive ventilation treatment in

  17. Liver biopsy

    Science.gov (United States)

    Biopsy - liver; Percutaneous biopsy ... the biopsy needle to be inserted into the liver. This is often done by using ultrasound. The ... the chance of damage to the lung or liver. The needle is removed quickly. Pressure will be ...

  18. Distribution of Foxp3(+) T cells in the liver and hepatic lymph nodes of goats and sheep experimentally infected with Fasciola hepatica.

    Science.gov (United States)

    Escamilla, A; Zafra, R; Pérez, J; McNeilly, T N; Pacheco, I L; Buffoni, L; Martínez-Moreno, F J; Molina-Hernández, V; Martínez-Moreno, A

    2016-10-30

    Foxp3 regulatory T cells (Tregs) are now considered to play a key role in modulation of immune responses during parasitic helminth infections. Immunomodulation is a key factor in Fasciola hepatica infection; however, the distribution and role of Foxp3(+) Tregs cells have not been investigated in F. hepatica infected ruminants. The aim of this study was to evaluate the presence of Foxp3(+) Tregs in the liver and hepatic lymph nodes from experimentally infected sheep and goats during acute and chronic stages of infection. Three groups of goats (n=6) and three groups of sheep (n=6) were used in this study. Goats in groups 1-2 and sheep in groups 4-5 were orally infected with metacercarie of ovine origin. Groups 1 and 4 were killed during the acute stage of the infection, at nine days post infection (dpi); groups 2 and 5 were killed during the chronic stage, at 15 and19 weeks post infection respectively (wpi). Groups 3 (goats) and 6 (sheep) were left as uninfected controls. Fluke burdens and liver damage were assessed and the avidin-biotin-complex method was used for the immunohistochemical study. At nine dpi in acute hepatic lesions, the number of both Foxp3(+) and CD3(+) T lymphocytes increased significantly in goats and sheep. In the chronic stages of infection (15-19wpi), the number of Foxp3(+) and CD3(+) T lymphocytes were also significantly increased with respect to control livers, particularly in portal spaces with severely enlarged bile ducts (response to adult flukes) while the increase was lower in granulomas, chronic tracts and smaller portal spaces (response to tissue damage). Foxp3(+) Tregs were increased in the cortex of hepatic lymph nodes of sheep (chronic infection) and goats (acute and chronic infection). The estimated proportion of T cells which were Foxp3+ was significantly increased in the large bile ducts and hepatic lymph node cortex of chronically infected goats but not sheep. This first report of the expansion of Foxp3(+) Tregs in acute and

  19. Migraine: etiology, risk, triggering, aggravating factors and clinical manifestations

    Directory of Open Access Journals (Sweden)

    Natalia Lindemann Carezzato

    2014-06-01

    Full Text Available This study aimed to identify the etiology and clinical manifestations of migraine. An integrative literature review was performed guided by the question: What is the evidence available in the literature about the etiology, signs and symptoms of migraine? The article search was conducted in the electronic databases PubMed and LILACS, considering publications in the period from 2006 to 2010. The selected articles were categorized and evaluated according to the level of evidence. One found 1,677 articles and 26 were selected for full reading. Most studies (84.6% consisted of a non-experimental design and were classified as evidence level IV. Although the clinical manifestations found in this study confirm the data available in the literature, it is noticed that migraine does not have well-established causes

  20. MR T1{rho} as an imaging biomarker for monitoring liver injury progression and regression: an experimental study in rats with carbon tetrachloride intoxication

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Feng; Wang, Yi-Xiang J.; Yuan, Jing; Deng, Min; Ahuja, Anil T. [Chinese University of Hong Kong, Department of Imaging and Interventional Radiology, Prince of Wales Hospital, Hong Kong SAR (China); Wong, Hing Lok [School of Public Health and Primary Care, Prince of Wales Hospital, The Chinese University of Hong Kong, Jockey Club Centre for Osteoporosis Care and Control, Hong Kong SAR (China); Chu, Eagle S.H.; Go, Minnie Y.Y.; Yu, Jun [Chinese University of Hong Kong, Institute of Digestive Disease and Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, Hong Kong SAR (China); Teng, Gao-Jun [Southeast University, Department of Radiology, Zhongda Hospital, Nanjing (China)

    2012-08-15

    Recently it was shown that the magnetic resonance imaging (MRI) T1{rho} value increased with the severity of liver fibrosis in rats with bile duct ligation. Using a rat carbon tetrachloride (CCl{sub 4}) liver injury model, this study further investigated the merit of T1{rho} relaxation for liver fibrosis evaluation. Male Sprague-Dawley rats received intraperitoneal injection of 2 ml/kg CCl{sub 4} twice weekly for up to 6 weeks. Then CCl{sub 4} was withdrawn and the animals were allowed to recover. Liver T1{rho} MRI and conventional T2-weighted images were acquired. Animals underwent MRI at baseline and at 2 days, 2 weeks, 4 weeks and 6 weeks post CCl{sub 4} injection, and they were also examined at 1 week and 4 weeks post CCl{sub 4} withdrawal. Liver histology was also sampled at these time points. Liver T1{rho} values increased slightly, though significantly, on day 2, and then increased further and were highest at week 6 post CCl{sub 4} insults. The relative liver signal intensity change on T2-weighted images followed a different time course compared with that of T1{rho}. Liver T1{rho} values decreased upon the withdrawal of the CCl{sub 4} insult. Histology confirmed the animals had typical CCl{sub 4} liver injury and fibrosis progression and regression processes. MR T1{rho} imaging can monitor CCl{sub 4}-induced liver injury and fibrosis. (orig.)

  1. Erosive arthritis and hepatic granuloma formation induced by peptidoglycan polysaccharide in rats is aggravated by prasugrel treatment.

    Directory of Open Access Journals (Sweden)

    Analia E Garcia

    Full Text Available Administration of the thienopyridine P2Y12 receptor antagonist, clopidogrel, increased the erosive arthritis induced by peptidoglycan polysaccharide (PG-PS in rats or by injection of the arthritogenic K/BxN serum in mice. To determine if the detrimental effects are caused exclusively by clopidogrel, we evaluated prasugrel, a third-generation thienopyridine pro-drug, that contrary to clopidogrel is mostly metabolized into its active metabolite in the intestine. Prasugrel effects were examined on the PG-PS-induced arthritis rat model. Erosive arthritis was induced in Lewis rats followed by treatment with prasugrel for 21 days. Prasugrel treated arthritic animals showed a significant increase in the inflammatory response, compared with untreated arthritic rats, in terms of augmented macroscopic joint diameter associated with significant signs of inflammation, histomorphometric measurements of the hind joints and elevated platelet number. Moreover, fibrosis at the pannus, assessed by immunofluorescence of connective tissue growth factor, was increased in arthritic rats treated with prasugrel. In addition to the arthritic manifestations, hepatomegaly, liver granulomas and giant cell formation were observed after PG-PS induction and even more after prasugrel exposure. Cytokine plasma levels of IL-1 beta, IL-6, MIP1 alpha, MCP1, IL-17 and RANTES were increased in arthritis-induced animals. IL-10 plasma levels were significantly decreased in animals treated with prasugrel. Overall, prasugrel enhances inflammation in joints and liver of this animal model. Since prasugrel metabolites inhibit neutrophil function ex-vivo and the effects of both clopidogrel and prasugrel metabolites on platelets are identical, we conclude that the thienopyridines metabolites might exert non-platelet effects on other immune cells to aggravate inflammation.

  2. Hemodynamics alterations during orthotopic liver experimental transplantation in pigs Alterações hemodinâmicas durante transplante hepático ortotópico experimental em suínos

    Directory of Open Access Journals (Sweden)

    Orlando Jorge Martins Torres

    2008-04-01

    Full Text Available PURPOSE: To describe the hemodynamics alterations during orthotopic liver transplantation in pigs. METHODS: In the period from April 2004 to December 2005, forty-four female Landrace pigs, weighting between 32 and 38 Kg were undergone to orthotopic liver transplantation. The animals were divided into two groups, donor and recipient pairs, which received whole liver grafts. The surgical procedure was divided into four parts: harvested, back-table, hepatectomy of the recipient and implantation. We analyze heart rate, blood gas, mean systemic arterial pressure (MAP-mmHg, central venous pressure, pH, Na-, K+, Cl-, Ca+ and urinary output. RESULTS: The mean anhepatic time was 69 min, cold ischemia was 252.2 min and back-table was 56.6 min. Blood pressure and heart rate dropped significantly during anhepatic phase and after revascularization. Blood gas and electrolytes alterations were observed during anhepatic and reperfusion phases. Although alterations were noted during these phases, the hemodynamic status was recovered and stabilized in the end of the surgery. CONCLUSIONS: Simplified technique of liver transplant was achieved and description of hemodynamic alterations was possible in pigs.OBJETIVO: Descrever as alterações hemodinâmicas que ocorrem durante o transplante hepático ortotópico experimental em suínos. MÉTODOS: No período de abril de 2004 a dezembro de 2005, quarenta porcos da raça Landrace, fêmeas, pesando entre 32 e 38Kg foram submetidos a transplante hepático ortotópico. Os animais foram divididos em dois grupos, doador e receptor, estes receberam enxerto total. O procedimento cirúrgico foi dividido em captação, cirurgia de banco, hepatectomia do receptor e implante do enxerto. Analisamos a freqüência cardíaca, gasometria, pressão arterial média (PAM-mmHg, pressão venosa central, pH, Na-, K+, Cl-, Ca+, e débito urinário. RESULTADOS: O tempo médio de fase anepática foi de 69 minutos, tempo de isquemia fria foi

  3. A clinical study of aprotinin blood anesthesia used in the surgery of liver cancer

    Institute of Scientific and Technical Information of China (English)

    易斌; 陶国才; 毕敏; 刘怀琼

    2004-01-01

    Objective: To investigate the role of aprotinin blood anesthesia used in hepatotomy. Methods: Patients with liver cancer undergoing hepatotomy were divided into two groups. In experimental group (40 patients) a loading dose with 1112 EPU aprotinin and maintained by 278 EPU/h was used until 2 h after operation. The control group (42 patients)was treated with 0.9% normal saline. The venous blood was withdrew for blood routine, thrombelastography and coagulable test at the time of preinduced, 1 h, 2 h and 4 h following the operation beginning, 6 h and 12 h after operation. The change of TEG and coagulable profile were monitored during the whole surgery. The volume of blood transfusion and hemorrhage between two groups were compared. Results: After the usage of aprotinin, the preoperative hypercoagulability of the experimental group was remitted and the coagulative state was kept relatively stable during the operation. However, hypercoagulability of the control group aggravated following the operation beginning and some of them switched to hypocoagulability. The volumes and rates of hemorrhage and transfusion were smaller in the experimental group than in the control group. Conclusion: Aprotinin can stabilize the coagulable state, reduce the volumes and rates of hemorrhage and transfusion, and is worth using in the surgery of operations of liver cancer.

  4. Aggravation and Stress in Parenting: Associations with Coparenting and Father Engagement among Resident Fathers

    Science.gov (United States)

    Bronte-Tinkew, Jacinta; Horowitz, Allison; Carrano, Jennifer

    2010-01-01

    This study uses a sample of 2,139 resident biological fathers from the Fragile Families and Child Wellbeing surveys (baseline and 12-month follow-up), to examine whether paternal aggravation and stress in parenting is associated with father engagement and coparenting and whether this association differs by father's socioeconomic status. Results of…

  5. Radiofrequency tissue ablation with cooled-tip electrodes:an experimental study in a bovine liver model on variables influencing lesion size

    Energy Technology Data Exchange (ETDEWEB)

    Han, Hyun Young [Eulgy Univ. Hospital, Seoul (Korea, Republic of); Lee, Jeong Min; Kim, Chong Soo [Chonbuk National Univ. Hospital, Chonju (Korea, Republic of)

    2001-03-01

    The purpose of this study was to determine the influence of various factors on the extent of thermal coagulation necrosis after radiofrequency (RF) tissue ablation using a cooled-tip electrode in bovine liver. RF ablation was induced by a monopolar 500 KHz-RF generator (CC-1; Radionics, Burlington, Mass., U.S.A.) and an 18-G cooled-tip with single or clustered electrodes. The ablation protocol involved a combination of varying current, ablation time, power output, gradual or abrupt increase of this out-put, and pulsed radiofrequency techniques. The maximum diameter of all thermal lesions which showed a color change was measured perpendicular to the electrode axis by two observers who reached their decisions by consensus. Twenty representative lesions were pathologically examined. With increasing current lesion diameter also increased, but above 1500 mA no further increase was induced. Extending the ablation time to 9 minutes for a single electrode and 15 minutes for a clustered electrode increased lesion diameter until a steady state was reached. Higher power levels caused larger lesions, but above 100 W no increase was observed. Ample exposure time coupled with a stepwise increase in power level induced a lesion larger than that resulting from an abrupt increase. Continuous pulsed RF with a high current led to increased coagulation necrosis diameter. These experimental findings may be useful thermotherapy. The data suggest that all involved factors significantly affect lesion size:if the factors are better understood, cancer thermotherapy can be better controlled.

  6. Liver regeneration.

    Science.gov (United States)

    Mao, Shennen A; Glorioso, Jaime M; Nyberg, Scott L

    2014-04-01

    The liver is unique in its ability to regenerate in response to injury. A number of evolutionary safeguards have allowed the liver to continue to perform its complex functions despite significant injury. Increased understanding of the regenerative process has significant benefit in the treatment of liver failure. Furthermore, understanding of liver regeneration may shed light on the development of cancer within the cirrhotic liver. This review provides an overview of the models of study currently used in liver regeneration, the molecular basis of liver regeneration, and the role of liver progenitor cells in regeneration of the liver. Specific focus is placed on clinical applications of current knowledge in liver regeneration, including small-for-size liver transplant. Furthermore, cutting-edge topics in liver regeneration, including in vivo animal models for xenogeneic human hepatocyte expansion and the use of decellularized liver matrices as a 3-dimensional scaffold for liver repopulation, are proposed. Unfortunately, despite 50 years of intense study, many gaps remain in the scientific understanding of liver regeneration.

  7. Sex bias in experimental immune-mediated, drug-induced liver injury in BALB/c mice: suggested roles for Tregs, estrogen, and IL-6.

    Directory of Open Access Journals (Sweden)

    Joonhee Cho

    Full Text Available BACKGROUND AND AIMS: Immune-mediated, drug-induced liver injury (DILI triggered by drug haptens is more prevalent in women than in men. However, mechanisms responsible for this sex bias are not clear. Immune regulation by CD4+CD25+FoxP3+ regulatory T-cells (Tregs and 17β-estradiol is crucial in the pathogenesis of sex bias in cancer and autoimmunity. Therefore, we investigated their role in a mouse model of immune-mediated DILI. METHODS: To model DILI, we immunized BALB/c, BALB/cBy, IL-6-deficient, and castrated BALB/c mice with trifluoroacetyl chloride-haptenated liver proteins. We then measured degree of hepatitis, cytokines, antibodies, and Treg and splenocyte function. RESULTS: BALB/c females developed more severe hepatitis (p<0.01 and produced more pro-inflammatory hepatic cytokines and antibodies (p<0.05 than did males. Castrated males developed more severe hepatitis than did intact males (p<0.001 and females (p<0.05. Splenocytes cultured from female mice exhibited fewer Tregs (p<0.01 and higher IL-1β (p<0.01 and IL-6 (p<0.05 than did those from males. However, Treg function did not differ by sex, as evidenced by absence of sex bias in programmed death receptor-1 and responses to IL-6, anti-IL-10, anti-CD3, and anti-CD28. Diminished hepatitis in IL-6-deficient, anti-IL-6 receptor α-treated, ovariectomized, or male mice; undetectable IL-6 levels in splenocyte supernatants from ovariectomized and male mice; elevated splenic IL-6 and serum estrogen levels in castrated male mice, and IL-6 induction by 17β-estradiol in splenocytes from naïve female mice (p<0.05 suggested that 17β-estradiol may enhance sex bias through IL-6 induction, which subsequently discourages Treg survival. Treg transfer from naïve female mice to those with DILI reduced hepatitis severity and hepatic IL-6. CONCLUSIONS: 17β-estradiol and IL-6 may act synergistically to promote sex bias in experimental DILI by reducing Tregs. Modulating Treg numbers may provide a

  8. [Xenotransplantation of the liver].

    Science.gov (United States)

    Winkler, M; Schlitt, H J

    1999-01-01

    The development of pigs transgenic for human regulators of complement activation resulted in the nearly total elimination of episodes of hyperacute rejection following discordant solid organ xenotransplantation. Following discordant heart or kidney transplantation, in subhuman primates, graft survival rates of up to several months can be observed. In contrast to these organs, the xenotransplantation of the liver is associated with the inherent problem of the immunological and metabolic compatibility of the large variety of xenoproteins generated. Based on a review of data mainly derived from experimental ex-vivo xenoliver perfusions in patients with hepatic coma, whole organ orthotopic or heterotopic liver xenotransplantation currently is not likely to become a relevant option for the treatment of patients with endstage liver failure. In contrast, clinical studies utilizing different forms of bioartificial liver assist devices are currently underway. Based on preliminary data published, this form of liver support therapy might enter the clinic in the near future.

  9. Metabolomic Analysis of Liver Tissue from the VX2 Rabbit Model of Secondary Liver Tumors

    OpenAIRE

    Ibarra, R.; Dazard, J-E.; Y. Sandlers; Rehman, F; Abbas, R.; Kombu, R.; Zhang, G-F; Brunengraber, H; Sanabria, J.

    2014-01-01

    Purpose. The incidence of liver neoplasms is rising in USA. The purpose of this study was to determine metabolic profiles of liver tissue during early cancer development. Methods. We used the rabbit VX2 model of liver tumors (LT) and a control group consisting of sham animals implanted with Gelfoam into their livers (LG). After two weeks from implantation, liver tissue from lobes with and without tumor was obtained from experimental animals (LT+/LT−) as well as liver tissue from controls (LG+...

  10. Liver Disease

    Science.gov (United States)

    ... stay still. Liver disease has many causes. Infection Parasites and viruses can infect the liver, causing inflammation ... beyond. National Institute of Diabetes and Digestive and Kidney Diseases. http://digestive.niddk.nih.gov/ddiseases/pubs/ ...

  11. Liver disease

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000205.htm Liver disease To use the sharing features on this page, please enable JavaScript. The term "liver disease" applies to many conditions that stop the ...

  12. Liver Diseases

    Science.gov (United States)

    Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis ...

  13. Residential characteristics aggravating infestation by Culex quinquefasciatus in a region of Northeastern Brazil

    Directory of Open Access Journals (Sweden)

    Juliana Cavalcanti Correia

    2012-12-01

    Full Text Available OBJECTIVE: Analyse how basic sanitation conditions, water supply and housing conditions affect the concentration of Culex quinquefasciatus METHODS: Populations of C. quinquefasciatus in 61 houses in the municipality of Olinda, PE, were monitored between October 2009 and October 2010. Observations were carried out in homes without the presence of preferred breeding sites in order to identify characteristics that may be aggravating factors for the development of the mosquito. Five aggravating factors were analysed: vegetation cover surrounding the home, number of residents/home, water storage, sewage drainage and water drainage. These characteristics were analysed in terms of presence or absence and as indicators of the degree of infestation, which was estimated through monitoring the concentration of eggs (oviposition traps - BR-OVT and adults (CDC light traps. RESULTS: Sewage drainage to a rudimentary septic tank or to the open air was the most frequent aggravating factor in the homes (91.8%, although the presence of vegetation was the only characteristic that significantly influenced the increase in the number of egg rafts (p = 0.02. The BR-OVT achieved positive results in 95.1% of the evaluations, with the presence of at least one egg raft per month. A total of 2,366 adults were caught, with a mosquito/room/night ratio of 32.9. No significant difference was found in the number of mosquitoes caught in the homes. CONCLUSIONS: Although the sanitation and water supply influence the population density of C. quinquefasciatus, residence features that are not usually considered in control measures can be aggravating factors in sustaining the mosquito population.

  14. [Activity of cytochromes P-450p and P-450h in liver microsomes and blood corticosteroid levels in experimental animals under the action of physical factors].

    Science.gov (United States)

    Zolotareva, T A; Gorchakova, G A; Konovalenko, V L; Konovalenko, L N; Grishanova, A Iu; Guliaeva, L F; Liakhovich, V V

    1992-05-01

    In experiments on male Wistar rats it has been found that physical factors applied in medicine (laser radiation of low intensity with wave length 0.89 microns, microwaves of centimeter range of 2450 MHz, and ultrasound of low intensity 880 KHz) changed catalytic activity of liver microsomal and rostenedione 16 alpha- and 6 beta-hydroxylating cytochromes P-450h and P-450p and blood corticosteroids level. Activities of these two steroid-metabolizing cytochromes decreased under ultrasonic skin application on liver region and increased under microwave and laser action. Contents of physiologically inactive form of corticosterone were not changed by the physical factors action while level of active hormone was increased under ultrasonic and microwave action. These findings suggest association of the activity of liver steroid-metabolizing cytochromes P-450 and level of physiologically active form of corticosterone in blood under physical factors skin application on liver region.

  15. An experimental method for rapid growth of liver in spleen. The survival and proliferation of chemically induced preneoplastic hepatocytes in spleen.

    OpenAIRE

    Finkelstein, S. D.; Lee, G.; Medline, A.; Tatematsu, M; Makowka, L.; Farber, E.

    1983-01-01

    Cellular suspensions (2 x 10(6) cells) of isolated preneoplastic liver cells, obtained from carcinogen-treated rats, were injected in the spleens of syngeneic rats divided into groups on the basis of no treatment, partial hepatectomy (PH), and/or feeding regimens including 2-acetylaminofluorene (AAF). Recipient rats undergoing both PH and AAF showed significantly more rapid proliferation of the preneoplastic liver cell implant, compared with other treatment groups and control. The theoretic b...

  16. Iron as a possible aggravating factor for osteopathy in itai-itai disease, a disease associated with chronic cadmium intoxication

    Energy Technology Data Exchange (ETDEWEB)

    Noda, M.; Yasuda, M.; Kitagawa, M. (Toyama Medical and Pharmaceutical Univ. (Japan))

    1991-03-01

    Itai-itai disease is thought to be the result of chronic cadmium (Cd) intoxication. We examined 23 autopsy cases of itai-itai disease and 18 cases of sudden death as controls. Urine and blood samples from 10 patients were collected before they died and revealed the presence of severe anemia and renal tubular injuries. Undecalcified sections of iliac bone were stained with Aluminon reagent, and ammonium salt of aurintricarboxylic acid, and Prussian blue reagent in all cases of itai-itai disease. These two reagents reacted at the same mineralization fronts. X-ray microanalysis revealed the presence of iron at mineralization fronts in itai-itai disease. Five patients showed evidence of hemosiderosis in the liver, spleen, and pancreas, probably as a result of post transfusion iron overload. Renal calculi and calcified aortic walls were also stained with Prussian blue reagent in several patients. Neither ferritin nor transferrin were visualized at mineralization fronts in itai-itai disease by immunohistochemical staining. These results suggest that iron is bound to calcium or to calcium phosphate by a physicochemical reaction. A marked osteomalacia was observed in 10 cases of itai-itai disease by histomorphometry. Regression analyses of data from cases of itai-itai disease suggested that an Aluminon-positive metal inhibited mineralization and that renal tubules were injured. Since bone Cd levels were increased in itai-itai disease, it is likely that renal tubules were injured by exposure to Cd. Therefore, stainable bone iron is another possible aggravating factor for osteopathy in itai-itai disease, and a synergistic effect between iron and Cd on mineralization is proposed.

  17. Experimental investigation of the perfusion of the liver with non-diffusible tracers: Differentiation of the arterial and portal-venous components by deconvolution analysis of first-pass time-activity curves

    Energy Technology Data Exchange (ETDEWEB)

    Szabo, Z.; Torsello, G.; Reifenrath, C.; Porschen, R.; Vosberg, H.

    1988-10-01

    The transfer function of the liver perfusion is an idealised time-activity curve that could be registered over the liver if a non-diffusible tracer would be injected directly into the abdominal aorta and no tracer recirculation would occur. The reproducibility of the transfer function was experimentally investigated in foxhounds. Both the routes of tracer application and the modes of data evaluation were varied and the perfusion was investigated under physiological and pathological conditions. The transfer function was calculated by deconvolution analysis of first-pass time-activity curves using the matrix regularisation method. The transfer function showed clearly distinguishable arterial and portal-venous components. Repeated peripheral venous and central aortic applications resulted in reproducible curves. In addition to the arterial and portal-venous components the subcomponents of the portal-venous component could also be identified in the transfer function after ligation of the appropriate vessels. The accuracy of the mathematical procedure was tested by computer simulations. The simulation studies demonstrated also that the matrix regularisation technique is suitable for deconvolution analysis of time-activity curves even when they are significantly contaminated by statistical noise. Calculation of the transfer function of liver perfusion and of its quantitative parameters seems thus to be a reliable method for non-invasive investigation of liver hemodynamics under physiological and pathological conditions.

  18. Proteoglycans in liver cancer

    Science.gov (United States)

    Baghy, Kornélia; Tátrai, Péter; Regős, Eszter; Kovalszky, Ilona

    2016-01-01

    Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain, such as a heparan, dermatan, chondroitin, or keratan sulfate, covalently attached to the protein core. These molecules are categorized based on their structure, localization, and function, and can be found in the extracellular matrix, on the cell surface, and in the cytoplasm. Cell-surface heparan sulfate proteoglycans, such as syndecans, are the primary type present in healthy liver tissue. However, deterioration of the liver results in overproduction of other proteoglycan types. The purpose of this article is to provide a current summary of the most relevant data implicating proteoglycans in the development and progression of human and experimental liver cancer. A review of our work and other studies in the literature indicate that deterioration of liver function is accompanied by an increase in the amount of chondroitin sulfate proteoglycans. The alteration of proteoglycan composition interferes with the physiologic function of the liver on several levels. This article details and discusses the roles of syndecan-1, glypicans, agrin, perlecan, collagen XVIII/endostatin, endocan, serglycin, decorin, biglycan, asporin, fibromodulin, lumican, and versican in liver function. Specifically, glypicans, agrin, and versican play significant roles in the development of liver cancer. Conversely, the presence of decorin could potentially provide protective effects. PMID:26755884

  19. Proteoglycans in liver cancer.

    Science.gov (United States)

    Baghy, Kornélia; Tátrai, Péter; Regős, Eszter; Kovalszky, Ilona

    2016-01-07

    Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain, such as a heparan, dermatan, chondroitin, or keratan sulfate, covalently attached to the protein core. These molecules are categorized based on their structure, localization, and function, and can be found in the extracellular matrix, on the cell surface, and in the cytoplasm. Cell-surface heparan sulfate proteoglycans, such as syndecans, are the primary type present in healthy liver tissue. However, deterioration of the liver results in overproduction of other proteoglycan types. The purpose of this article is to provide a current summary of the most relevant data implicating proteoglycans in the development and progression of human and experimental liver cancer. A review of our work and other studies in the literature indicate that deterioration of liver function is accompanied by an increase in the amount of chondroitin sulfate proteoglycans. The alteration of proteoglycan composition interferes with the physiologic function of the liver on several levels. This article details and discusses the roles of syndecan-1, glypicans, agrin, perlecan, collagen XVIII/endostatin, endocan, serglycin, decorin, biglycan, asporin, fibromodulin, lumican, and versican in liver function. Specifically, glypicans, agrin, and versican play significant roles in the development of liver cancer. Conversely, the presence of decorin could potentially provide protective effects.

  20. 13.LIVER AND BILIARY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    13.2.Liver cirrhosis and fatty liver930691 Experimental observation of high portal ve-nous resistance in dogs.WANG Weimin,etal.Dept Surg,1st Teach Hosp,Beijing Med Univ,Beijing,100034 Natl Med J China 1993;73(6):349—351.To study the relationship between portal resistanceand formation of portal hypertension,we designed a

  1. What Is Liver Cancer?

    Science.gov (United States)

    ... Treatment? Liver Cancer About Liver Cancer What Is Liver Cancer? Cancer starts when cells in the body ... structure and function of the liver. About the liver The liver is the largest internal organ. It ...

  2. Experimental fatty liver hemorrhagic syndrome in laying hens%人工诱发产蛋鸡脂肪肝出血综合征的研究

    Institute of Scientific and Technical Information of China (English)

    董晓芳; 佟建明; 常铁生; 李娟娟; 张琪

    2011-01-01

    通过外源性注射雌激素、高能低蛋白日粮及不同油脂来源的高能日粮人工诱发蛋鸡FLHS。90只40周龄海兰灰商品蛋鸡常规笼养,随机分为9组(10×9):基础日粮组、基础日粮注射玉米油组、基础日粮注射β-雌二醇组;高能低蛋白日粮组、高能低蛋白注射玉米油组、高能低蛋白日粮注射伊雌二醇组;牛油高能日粮组、鸡油高能目粮组、豆油高能日粮组。每天记录产蛋数,每周记录采食量,第24天称重后剖杀所有试验鸡,观察肝脏出血程度。结果表明,各组采食量、增重没有显著差异。注射β-雌二醇极显著降低了产蛋率(P〈0.01),注射玉米油和日%To induce experimentally fatty liver hemorrhagic syndromes (FLHS) in laying hens by exogenous β- estradiol injection,high energy and low-protein level diets, and high-energy diets with different kinds of fat. Ninety 40 week Hailanhui commercial laying hens were randomly allocated to 9 groups (10 × 9) : Group 1 fed basal diet,group 2 fed basal diet and injected intramuscularly with corn oil,group 3 fed basal diet and injected i. m. β- estradiol,group 4 fed high-energy and low-protein diets,group 5 fed high-energy and low-protein diets and injected i. m. corn oil,group 6 fed high-energy and low-protein diets and iniected i. m. β-estradiol, group 7 fed tallow high-energy diet,group 8 fed chicken fat high-energy diet,group 9 fed bean oil high energy diet. Egg production was recorded daily and feed intake recorded weekly. At the 24 day all birds were weighed, sacrificed,and hepatic hemorrhage were observed. All treat ment had no significant effect on feed intake and weight gain (P〉0.05) ;exogenous β- estradiol injection decreased significantly egg production (P〈0.01), while corn oil injection and diet treatment had no effect on egg production. The injection of β- estradiol increased significantly hepatic hemorrhage score (P〈0.01

  3. Liver Transplant

    Science.gov (United States)

    ... Liver Disease & NASH Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Biliary Atresia Cirrhosis Hemochromatosis Hepatitis A through E (Viral Hepatitis) Hepatitis ...

  4. Sodium chloride promotes pro-inflammatory macrophage polarization thereby aggravating CNS autoimmunity.

    Science.gov (United States)

    Hucke, Stephanie; Eschborn, Melanie; Liebmann, Marie; Herold, Martin; Freise, Nicole; Engbers, Annika; Ehling, Petra; Meuth, Sven G; Roth, Johannes; Kuhlmann, Tanja; Wiendl, Heinz; Klotz, Luisa

    2016-02-01

    The increasing incidence in Multiple Sclerosis (MS) during the last decades in industrialized countries might be linked to a change in dietary habits. Nowadays, enhanced salt content is an important characteristic of Western diet and increased dietary salt (NaCl) intake promotes pathogenic T cell responses contributing to central nervous system (CNS) autoimmunity. Given the importance of macrophage responses for CNS disease propagation, we addressed the influence of salt consumption on macrophage responses in CNS autoimmunity. We observed that EAE-diseased mice receiving a NaCl-high diet showed strongly enhanced macrophage infiltration and activation within the CNS accompanied by disease aggravation during the effector phase of EAE. NaCl treatment of macrophages elicited a strong pro-inflammatory phenotype characterized by enhanced pro-inflammatory cytokine production, increased expression of immune-stimulatory molecules, and an antigen-independent boost of T cell proliferation. This NaCl-induced pro-inflammatory macrophage phenotype was accompanied by increased activation of NF-kB and MAPK signaling pathways. The pathogenic relevance of NaCl-conditioned macrophages is illustrated by the finding that transfer into EAE-diseased animals resulted in significant disease aggravation compared to untreated macrophages. Importantly, also in human monocytes, NaCl promoted a pro-inflammatory phenotype that enhanced human T cell proliferation. Taken together, high dietary salt intake promotes pro-inflammatory macrophages that aggravate CNS autoimmunity. Together with other studies, these results underline the need to further determine the relevance of increased dietary salt intake for MS disease severity.

  5. Cynomolgus monkeys (Macaca fascicularis) experimentally infected with B19V and hepatitis A virus: no evidence of the co-infection as a cause of acute liver failure

    Science.gov (United States)

    Leon, Luciane Almeida Amado; Marchevsky, Renato Sergio; Gaspar, Ana Maria Coimbra; Garcia, Rita de Cassia Nasser Cubel; de Almeida, Adilson José; Pelajo-Machado, Marcelo; de Castro, Tatiana Xavier; do Nascimento, Jussara Pereira; Brown, Kevin E; Pinto, Marcelo Alves

    2016-01-01

    This study was conducted to analyse the course and the outcome of the liver disease in the co-infected animals in order to evaluate a possible synergic effect of human parvovirus B19 (B19V) and hepatitis A virus (HAV) co-infection. Nine adult cynomolgus monkeys were inoculated with serum obtained from a fatal case of B19V infection and/or a faecal suspension of acute HAV. The presence of specific antibodies to HAV and B19V, liver enzyme levels, viraemia, haematological changes, and necroinflammatory liver lesions were used for monitoring the infections. Seroconversion was confirmed in all infected groups. A similar pattern of B19V infection to human disease was observed, which was characterised by high and persistent viraemia in association with reticulocytopenia and mild to moderate anaemia during the period of investigation (59 days). Additionally, the intranuclear inclusion bodies were observed in pro-erythroblast cell from an infected cynomolgus and B19V Ag in hepatocytes. The erythroid hypoplasia and decrease in lymphocyte counts were more evident in the co-infected group. The present results demonstrated, for the first time, the susceptibility of cynomolgus to B19V infection, but it did not show a worsening of liver histopathology in the co-infected group. PMID:27074255

  6. Viola Playing May Be a Strong Aggravating Factor for Temporomandibular Disorder

    Directory of Open Access Journals (Sweden)

    Mahmut Alpayci

    2014-12-01

    Full Text Available Temporomandibular disorder (TMD is the general term used to describe the symptoms originated from temporomandibular joint region. The most common symptom of the disorder is pain during mandibular movement. Etiology of TMD is multifactorial. Several factors such as trauma, occlusal discrepancies, stress, parafunctions, hypermobility, and heredity can make one more vulnerable to this disorder. It has been reported that viola playing might be a predisposing factor for TMD. In this article, we present a 24 year old male patient suffering from TMD symptoms exacerbated by viola playing and emphasize that viola playing may be a powerful aggravating factor for TMD.

  7. Environmental air pollution is an aggravating event for sudden unexpected death in epilepsy

    Directory of Open Access Journals (Sweden)

    Carla A. Scorza

    2013-10-01

    Full Text Available It is extremely difficult to estimate the occurrence of sudden unexpected death in epilepsy (SUDEP. On the other hand, discovering and carefully evaluating new risk factors that may contribute to the onset of cardiovascular abnormalities in people with refractory epilepsy may prevent fatal events in these individuals. In this context, we should not ignore that urban air pollution is a leading problem for environmental health and is able to cause serious cardiovascular dysfunctions that culminate in sudden death. In this regard, we aimed to determine whether environmental exposure to air pollution is an aggravating event for SUDEP.

  8. Liver spots

    Science.gov (United States)

    Liver spots are changes in skin color that occur in older skin. The coloring may be due to aging, exposure to the sun or other sources of ultraviolet light, or causes that are not known. Liver spots are very common after age 40. They occur ...

  9. 改进小体积肝移植供肝大鼠模型建立方法的实验研究%Experimental study of improved methods of liver lobe resection for liver transplantation in rats

    Institute of Scientific and Technical Information of China (English)

    王晓明; 周才明; 李君

    2009-01-01

    Objective To explore an effective and viable way to establish small-for-size liver transplantation model in rats.Methods Male Lewis rats were used as donors and recipients,the grafts were implanted according to Kamada's 2-coff method.Animals were divided into the following groups:Group I (n=28):30% size graft liver transplantation using a median lobe graft,with left lobe,right lobe,caudate lobe and triangle lobe removed in situ;Group Ⅱ (n=36) :30% size graft liver transplantation using a median lobe graft,with an improved technic of lobe resection.7-day survival rat and the technical complications including bleeding,IVC or portal vein stricture and bile leakage were compared between the groups.Results Compared to the Group Ⅰ,the incidence of IVC stricture was significantly decreased in the Group Ⅱ.Other complications showed no significant difference between the two groups.No significant difference were observed in the 7-day survival rate between the two groups(33%,9/28 vs 60%,21/36),( X2 = 0.272,P > 0.05 ),though Group Ⅱ had more survivors 7 days after liver transplantation.Conclusion With improved method of lobe resection,more effective and viable 30% small-for-size rat liver transplantation model can be established.%目的 探讨改进切肝技术,以建立更可靠的小体积肝移植供肝大鼠模型.方法 以Kamada的"二袖套法"为基础,建立30%小体积肝移植中叶供肝大鼠模型.实验分两组:Ⅰ组(28只),常规方法切肝.以中叶作供肝;Ⅱ组(36只),改进为左叶和右叶的切肝方法,余方法步骤同Ⅰ组.观察两组手术并发症和7 d生存率.结果 Ⅱ组肝后下腔静脉狭窄的发生率明显低于Ⅰ组(P<0.05),其他并发症发生率两组间无明显差异(P>0.05).术后7 d生存率Ⅱ组(60%,21/36)高于Ⅰ组(33%,9/28),但差异未显示有统计学意义(x2=0.272,P>0.05).结论 采用中叶供肝、改进切肝技术,可以建立更稳定可靠的部分体积肝移植供肝大鼠模型.

  10. Orally delivered β-glucans aggravate dextran sulfate sodium (DSS)-induced intestinal inflammation.

    Science.gov (United States)

    Heinsbroek, Sigrid E M; Williams, David L; Welting, Olaf; Meijer, Sybren L; Gordon, Siamon; de Jonge, Wouter J

    2015-12-01

    β-Glucans have beneficial health effects due to their immune modulatory properties. Oral administration of β-glucans affects tumour growth, microbial infection, sepsis, and wound healing. We hypothesized that pre-treatment with orally delivered soluble and particulate β-glucans could ameliorate the development of aggravate dextran sulfate sodium (DSS) induced intestinal inflammation. To study this, mice were orally pre-treated with β-glucans for 14 days. We tested curdlan (a particulate β-(1,3)-glucan), glucan phosphate (a soluble β-(1,3)-glucan), and zymosan (a particle made from Saccharomyces cerevisiae, which contains around 55% β-glucans). Weight loss, colon weight, and feces score did not differ between β-glucan and vehicle treated groups. However, histology scores indicated that β-glucan-treated mice had increased inflammation at a microscopic level suggesting that β-glucan treatment worsened intestinal inflammation. Furthermore, curdlan and zymosan treatment led to increased colonic levels of inflammatory cytokines and chemokines, compared to vehicle. Glucan phosphate treatment did not significantly affect cytokine and chemokine levels. These data suggest that particulate and soluble β-glucans differentially affect the intestinal immune responses. However, no significant differences in other clinical colitis scores between soluble and particulate β-glucans were found in this study. In summary, β-glucans aggravate the course of dextran sulfate sodium (DSS)-induced intestinal inflammation at the level of the mucosa.

  11. Consumption of Mercury-contaminated Rice Induces Oxidative Stress and Free Radical Aggravation in Rats

    Institute of Scientific and Technical Information of China (English)

    XIU-LING JI; GUI-WEN JIN; JIN-PING CHENG; WEN-HUA WANG; JING LU; LI-YA QU

    2007-01-01

    Objective To study the oxidative stress induced by consumption of mercury-contaminated rice in rats, and to assess the possible public health risk of mercury contamination in Wanshan mining area. Methods Sprague Dawley rats were fed the mercury-contaminated rice produced from Wanshan area for 90 days. The antioxidant status and the free radicals in rat serum were evaluated. Results High mercury accumulation in organs of rats fed the mercury-contaminated rice confirmed the server pollution of mercury in Wanshan mining area. The intensity of electron spin resonance (ESR) signal increased by 87.38% in rats fed the rice from Wanshan compared with that in the control rats fed the rice from Shanghai, suggesting that chronic dietary consumption of rice from mercury mining area could induce an aggravation of free radicals. Feeding the mercury-contaminated rice was associated with significant decreases in the antioxidant enzymatic activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and concentration of serum nitric oxide (NO), but it had no effect on serum nitric oxide synthase (NOS) activity. Feeding the mercury-contaminated rice raised the level of serum malonyldialdehyde (MDA), indicating the occurrence of oxidative stress. Conclusion The long-term dietary consumption of mercury-contaminated rice induces the aggravation of free radicals and exerts oxidative stress.

  12. Chronic hypertension aggravates heat stress-induced brain damage: possible neuroprotection by cerebrolysin.

    Science.gov (United States)

    Muresanu, Dafin Fior; Zimmermann-Meinzingen, Sibilla; Sharma, Hari Shanker

    2010-01-01

    Whole body hyperthermia (WBH) aggravates brain edema formation and cell damage in chronic hypertensive rats compared with normotensive animals. In this investigation, we examined the influence of cerebrolysin on WBH-induced edema formation and brain pathology in hypertensive and normotensive rats. Rats subjected to 4 h WBH at 38 degrees C in a biological oxygen demand (BOD) incubator showed breakdown of the blood-brain barrier (BBB), reduced cerebral blood flow (CBF), edema formation and cell injuries in several parts of the brain. These effects were further aggravated in chronic hypertensive rats (two-kidney one clip model (2K1C), for 4 weeks) subjected to WBH. Pretreatment with cerebrolysin (5 mL/kg, 24 h and 30 min before heat stress) markedly attenuated the BBB dysfunction and brain pathology in normal animals. However, in hypertensive animals, a high dose of cerebrolysin (10 mL/kg, 24 h and 30 min before heat stress) was needed to attenuate WBH-induced BBB dysfunction and brain pathology. These observations indicate that heat stress could affect differently in normal and hypertensive conditions. Furthermore, our results suggest that patients suffering from various chronic cardiovascular diseases may respond differently to hyperthermia and to neuroprotective drugs, e.g., cerebrolysin not reported earlier.

  13. An Atherogenic Paigen-Diet Aggravates Nephropathy in Type 2 Diabetic OLETF Rats.

    Directory of Open Access Journals (Sweden)

    Masanori Nozako

    Full Text Available Diabetic nephropathy develops in association with hyperglycemia, is aggravated by atherogenic factors such as dyslipidemia, and is sometimes initiated before obvious hyperglycemia is seen. However, the precise mechanisms of progression are still unclear. In this study, we investigated the influence of an atherogenic Paigen diet (PD on the progression of nephropathy in spontaneous type 2 diabetic OLETF rats. Feeding PD to male OLETF rats for 12 weeks caused an extensive increase in excretion of urinary albumin and markers of tubular injury such as KIM-1 and L-FABP, accompanied by mesangial expansion and tubular atrophy. PD significantly increased plasma total cholesterol concentration, which correlates well with increases in urine albumin excretion and mesangial expansion. Conversely, PD did not change plasma glucose and free fatty acid concentrations. PD enhanced renal levels of mRNA for inflammatory molecules such as KIM-1, MCP-1, TLR4 and TNF-α and promoted macrophage infiltration and lipid accumulation in the tubulointerstitium and glomeruli in OLETF rats. Intriguingly, PD had little effect on urine albumin excretion and renal morphology in normal control LETO rats. This model may be useful in studying the complex mechanisms that aggravate diabetic nephropathy in an atherogenic environment.

  14. An Atherogenic Paigen-Diet Aggravates Nephropathy in Type 2 Diabetic OLETF Rats

    Science.gov (United States)

    Nozako, Masanori; Koyama, Takashi; Nagano, Chifumi; Sato, Makoto; Matsumoto, Satoshi; Mitani, Kiminobu; Yasufuku, Reiko; Kohashi, Masayuki; Yoshikawa, Tomohiro

    2015-01-01

    Diabetic nephropathy develops in association with hyperglycemia, is aggravated by atherogenic factors such as dyslipidemia, and is sometimes initiated before obvious hyperglycemia is seen. However, the precise mechanisms of progression are still unclear. In this study, we investigated the influence of an atherogenic Paigen diet (PD) on the progression of nephropathy in spontaneous type 2 diabetic OLETF rats. Feeding PD to male OLETF rats for 12 weeks caused an extensive increase in excretion of urinary albumin and markers of tubular injury such as KIM-1 and L-FABP, accompanied by mesangial expansion and tubular atrophy. PD significantly increased plasma total cholesterol concentration, which correlates well with increases in urine albumin excretion and mesangial expansion. Conversely, PD did not change plasma glucose and free fatty acid concentrations. PD enhanced renal levels of mRNA for inflammatory molecules such as KIM-1, MCP-1, TLR4 and TNF-α and promoted macrophage infiltration and lipid accumulation in the tubulointerstitium and glomeruli in OLETF rats. Intriguingly, PD had little effect on urine albumin excretion and renal morphology in normal control LETO rats. This model may be useful in studying the complex mechanisms that aggravate diabetic nephropathy in an atherogenic environment. PMID:26606054

  15. Mesenchymal stromal cell implantation for stimulation of long bone healing aggravates Staphylococcus aureus induced osteomyelitis.

    Science.gov (United States)

    Seebach, Elisabeth; Holschbach, Jeannine; Buchta, Nicole; Bitsch, Rudi Georg; Kleinschmidt, Kerstin; Richter, Wiltrud

    2015-07-01

    Large bone defects requiring long-term osteosynthetic stabilization or repeated surgeries show a considerable rate of infection. Mesenchymal stromal cells (MSCs) have been successfully used to enhance bone regeneration, but their powerful immunomodulatory effects may impose an enhanced risk for osteomyelitis development. In order to unravel whether implantation of MSCs aggravates a simultaneous bone infection, a hydrogel-supported osteomyelitis ostectomy model was developed in which rats received a femoral bone defect with rigid plate-fixation. After fibrin-assisted transfer of Staphylococcus aureus (SA), effects of MSC implantation on osteomyelitis development were quantified over 3-4 weeks. All SA-infected animals developed an acute local osteomyelitis with significantly increased blood neutrophil count, abscess formation and bone destruction. MSC-treatment of infected defects aggravated osteomyelitis according to a significantly elevated osteomyelitis score and enhanced distal bone loss with spongy alteration of cortical bone architecture. Increased attraction of macrophages, osteoclasts and regulation of pro- and anti-inflammatory mediators were potential MSC actions. Overall trophic actions of MSCs implanted into non-sterile bone defects may enhance an infection and/or exacerbate osteomyelitis. Studies on antibiotic carrier augmentation or antibiotic treatment are warranted to decide whether MSC implantation is a safe and promising therapy for orthopedic implant-stabilized bone defects at high risk for development of infection.

  16. Fucoidan ameliorates steatohepatitis and insulin resistance by suppressing oxidative stress and inflammatory cytokines in experimental non-alcoholic fatty liver disease.

    Science.gov (United States)

    Heeba, Gehan H; Morsy, Mohamed A

    2015-11-01

    Fucoidan, a sulfated polysaccharide derived from brown seaweeds, possesses a wide range of pharmacological properties. In the present study, we investigated the therapeutic effect of fucoidan on non-alcoholic fatty liver disease (NAFLD) in rats. Rats were fed a high-fat diet (HFD) for 12 weeks to induce NAFLD. Oral administrations of fucoidan (100mg/kg, orally), metformin (200mg/kg, orally) or the vehicle were started in the last four weeks. Results showed that administration of fucoidan for 4 weeks attenuated the development of NAFLD as evidenced by the significant decrease in liver index, serum liver enzymes activities, serum total cholesterol and triglycerides, fasting serum glucose, insulin, insulin resistance, and body composition index. Further, fucoidan decreased hepatic malondialdehyde as well as nitric oxide concentrations, and concomitantly increased hepatic reduced glutathione level. In addition, the effect of fucoidan was accompanied with significant decrease in hepatic mRNA expressions of tumor necrosis factor-α, interleukins-1β and matrix metalloproteinase-2. Furthermore, histopathological examination confirmed the effect of fucoidan. In conclusion, fucoidan ameliorated the development of HFD-induced NAFLD in rats that may be, at least partly, related to its hypolipidemic, insulin sensitizing, antioxidant and anti-inflammatory mechanisms.

  17. Liver metastases

    Science.gov (United States)

    ... no symptoms. When symptoms occur, they may include: Decreased appetite Confusion Fever , sweating Jaundice (yellowing of the skin ... can include: Blockage of the flow of bile Decreased appetite Fever Liver failure (usually only in the late ...

  18. Enlarged Liver

    Science.gov (United States)

    ... A blood sample is tested to determine liver enzyme levels. This can give clues about the health ... prescription medications. Limit contact with chemicals. Use aerosol cleaners, insecticides and other toxic chemicals only in well- ...

  19. Rosiglitazone Intervene Nonalacoholic Fatty Liver Disease Rats' Experimental Study%罗格列酮干预大鼠非酒精性脂肪肝

    Institute of Scientific and Technical Information of China (English)

    田培营; 王炳芳; 樊晓明; 何双涛

    2011-01-01

    Objective:To observe the variation of insulin resistance and plastic apolipoprotein-CII, apolipoprotein-CIII content and the plastic activity of lipoprotein lipase, hepatic lipase, apolipoprotein-BlOOmRNA representation and patholotic varation of hepatic tissue of the rosiglitazone maleate therapy of nonalcoholic fatty liver disease rats. Methods: Male Sprague Dawley rats fed with hpysi-fat and hpysi-cholesterol forage for establishing nonalacoholic fatty liver disease model for 8 weeks, the nonala-coholic fatty liver disease rats were intervened by rosiglitazone for 4 weeks after the model was successfully made; the rats hepatic tissue pathological variation were observed by hematoxylin-eosin staining, apolipoprotein-Bl00mRNA representation were tested by reverse transcriptase PCR, apolipoprotein-CII, apolipoprotein-CIII and insulin content were detected using enzyme-linked immunosorbent-assay, plastic activity of lipoprotein lipase, hepatic lipase were tested by enzyme method, the fasting blood glucose were detected by sudden glucose determinator, according to Homeostatic model assessment Insulin resistance in-dex(HOMA-IR) IR= FPG(mmol/L)FINS(mIU/L)/22. 5 calculating the insulin resistance index. Results: After the fatty liver rats treated with rosiglitazone maleate, the rats' insulin resistance and hepatic cell fatty denaturation were lightened, apoli-poprotein-Bl00 mRNA representation of hepatic tissue increased, plastic apolipoprotein-CII content raised, apolipoprotein-CIII content decreased, plastic activity of lipoprotein lipase and hepatic lipase raised. Conclusions: Rosiglitazone maleate can lighten the fatty liver rats insulin resistance and hepatic cell fatty denaturation, amendment lipid metabolic disorder of the fatty liver rats.%目的:用马采酸罗格列酮治疗非酒精性脂肪肝大鼠,观察治疗前后胰岛素抵抗情况、血浆载脂蛋白CⅡ (ApoCⅡ)、载脂蛋白CⅢ(ApoCⅢ)的含量变化和脂蛋白脂肪酶(LPL)、肝脂肪酶(HL

  20. Cystic echinococcosis of the liver and lung treated by radiofrequency thermal ablation: An ex-vivo pilot experimental study in animal models

    Institute of Scientific and Technical Information of China (English)

    Vincenzo Lamonaca; Antonino Virga; Marta Ida Minervini; Roberta Di Stefano; Alessio Provenzani; Pietro Tagliareni; Giovanna Fleres; Angelo Luca; Giovanni Vizzini; Ugo Palazzo; Bruno Gridelli

    2009-01-01

    AIM: To evaluate radiofrequency thermal ablation (RTA) for treatment of cystic echinococcosis in animal models (explanted organs). METHODS: Infected livers and lungs from slaughtered animals, 10 bovine and two ovine, were collected. Cysts were photographed, and their volume, cyst content, germinal layer adhesion status, wall calcification and presence of daughter or adjacent cysts were evaluated by ultrasound. Some cysts were treated with RTA at 150 W, 80℃, 7 min. Temperature was monitored inside and outside the cyst. A second needle was placed inside the cyst for pressure stabilization. After treatment, all cysts were sectioned and examined by histology. Cysts were defined as alive if a preserved germinal layer at histology was evident, and as successfully treated if the germinal layer was necrotic. RESULTS: The subjects of the study were 17 cysts (nine hepatic and eight pulmonary), who were treated with RTA. Pathology showed 100% success rate in both hepatic (9/9) and lung cysts (8/8); immediate volume reduction of at least 65%; layer of host tissue necrosis outside the cyst, with average extension of 0.64 cm for liver and 1.57 cm for lung; and endocyst attached to the pericystium both in hepatic and lung cysts with small and focal de novo endocyst detachment in just 3/9 hepatic cysts.CONCLUSION: RTA appears to be very effective in killing hydatid cysts of explanted liver and lung.Bile duct and bronchial wall necrosis, persistence of endocyst attached to pericystium, should help avoid or greatly decrease in vivo post-treatment fistula occurrence and consequent overlapping complications that are common after surgery or percutaneous aspiration,injection and reaspiration. In vivo studies are required to confirm and validate this new therapeutic approach.

  1. Experimental data suggesting that inflammation mediated rat liver mitochondrial dysfunction results from secondary hypoxia rather than from direct effects of inflammatory mediators

    Directory of Open Access Journals (Sweden)

    Adelheid eWeidinger

    2013-06-01

    Full Text Available Systemic inflammatory response (SIR comprises direct effects of inflammatory mediators (IM and indirect effects, such as secondary circulatory failure which results in tissue hypoxia (HOX. These two key components, SIR and HOX, cause multiple organ failure (MOF. Since HOX and IM occur and interact simultaneously in vivo, it is difficult to clarify their individual pathological impact. To eliminate this interaction, precision cut liver slices (PCLS were used in this study aiming to dissect the effects of HOX and IM on mitochondrial function, integrity of cellular membrane and the expression of genes associated with inflammation. HOX was induced by incubating PCLS or rat liver mitochondria at pO2<1% followed by reoxygenation (HOX/ROX model. Inflammatory injury was stimulated by incubating PCLS with IM (IM model. We found upregulation of inducible nitric oxide synthase (iNOS expression only in the IM model, while heme oxygenase 1 (HO-1 expression was upregulated only in the HOX/ROX model. Elevated expression of interleukin 6 (IL-6 was found in both models reflecting converging pathways regulating the expression of this gene. Both models caused damage to hepatocytes resulting in the release of alanine aminotransferase (ALT. The leakage of aspartate aminotransferase (AST was observed only during the hypoxic phase in the HOX/ROX model. The reoxygenation phase of HOX, but not IM, drastically impaired mitochondrial electron supply via complex I and II. Additional experiments performed with isolated mitochondria showed that free iron, released during HOX, is likely a key prerequisite of mitochondrial dysfunction induced during the reoxygenation phase. Our data suggests that mitochondrial dysfunction, previously observed in in vivo SIR-models is the result of secondary circulatory failure inducing HOX rather than the result of a direct interaction of IM with liver cells.

  2. Liver function

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008308 Study on transplantation of induced bone marrow mesenchymal stem cells via a series of the treatment of chronic liver injury. SUN Yan(孙艳), et al. Dept Gastroenterol, 1st Hosp, Jilin Univ, Changchun 130021. Chin J Dig 2008;28(3):171-174.Objective To investigate the efficacy of transplantation of induced bone marrow mesenchymal stem cells(MSCs)via a series of treatment of chronic liver injury.Methods MSCs were isolated and expanded by density

  3. Chronic Liver Failure after Treatment with Infliximab for Ankylosing Spondylitis in a Patient with Hepatitis B

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    A 50-year-old man with ankylosing spondylitis was treated successfully with inlfiximab, who was also a HBV carrier for about twenty-ifve years. After injection with inlfiximab for four times, he developed jaundice and HBV DNA was detectable in serum. Serum aminotransferase and total bilirubin levels were higher than normal. Then he was hospitalized and treated with entacavir and Chinese herb medicine. But his liver damage aggravated and was diagnosed as acute on chronic liver failure. Finally, liver transplantation was carried out and he was cured successfully.

  4. Acute patellofemoral pain: aggravating activities, clinical examination, MRI and ultrasound findings

    DEFF Research Database (Denmark)

    Brushoj, C.; Holmich, P.; Nielsen, M.B.;

    2008-01-01

    Objective: To investigate acute anterior knee pain caused by overuse in terms of pain location, aggravating activities, findings on clinical examination and ultrasound/MRI examination. To determine if acute anterior knee pain caused by overuse should be classified as a subgroup of patellofemoral...... pain syndrome (PFPS). Methods: In a observational study design 30 army recruits with anterior knee pain (mean duration of pain 4 weeks) were examined using the PFPS pain severity scale (PSS), knee pain diagrams, standardised clinical examination, ultrasound and MRI examinations. Results: On PSS typical......%)), but other synovial covered structures including the fat pad of Hoffa (12 patients (40%)), the medial plica and the joint line (12 patients (40%)) were also involved. Only eight patients (27%) experienced pain on the patellofemoral compression test. Only discrete changes was detected on MRI...

  5. Obesity does not aggravate vitrification injury in mouse embryos: a prospective study

    Directory of Open Access Journals (Sweden)

    Ma Wenhong

    2012-08-01

    Full Text Available Abstract Background Obesity is associated with poor reproductive outcomes, but few reports have examined thawed embryo transfer in obese women. Many studies have shown that increased lipid accumulation aggravates vitrification injury in porcine and bovine embryos, but oocytes of these species have high lipid contents (63 ng and 161 ng, respectively. Almost nothing is known about lipids in human oocytes except that these cells are anecdotally known to be relatively lipid poor. In this regard, human oocytes are considered to be similar to those of the mouse, which contain approximately 4 ng total lipids/oocyte. To date, no available data show the impact of obesity on vitrification in mouse embryos. The aim of this study was to establish a murine model of maternal diet-induced obesity and to characterize the effect of obesity on vitrification by investigating the survival rate and embryo developmental competence after thawing. Methods Prospective comparisons were performed between six–eight-cell embryos from obese and normal-weight mice and between fresh and vitrified embryos. Female C57BL/6 mice were fed standard rodent chow (normal-weight group or a high-fat diet (obese group for 6 weeks. The mice were mated, zygotes were collected from oviducts and cultured for 3 days, and six–eight-cell embryos were then selected to assess lipid content in fresh embryos and to evaluate differences in apoptosis, survival, and development rates in response to vitrification. Results In fresh embryos from obese mice, the lipid content (0.044 vs 0.030, Pvs.9.3%, Pvs. 93.1%, P Conclusions This study demonstrated that differences in survival and developmental rates between embryos from obese and normal-weight mice were eliminated after vitrification. Thus, maternal obesity does not aggravate vitrification injury, but obesity alone greatly impairs pre-implantation embryo survival and development.

  6. Calreticulin Translocation Aggravates Endoplasmic Reticulum Stress-associated Apoptosis during Cardiomyocyte Hypoxia/Reoxygenation

    Institute of Scientific and Technical Information of China (English)

    Fei-Fei Xu; Xiu-Hua Liu

    2015-01-01

    Background:Calreticulin (CRT) is major Ca2+-binding chaperone mainly resident in the endoplasmic reticulum (ER) lumen.Recently,it has been shown that non-ER CRT regulates a wide array of cellular responses.We previously found that CRT was up-regulated during hypoxia/reoxygenation (H/R) and this study was aimed to investigate whether CRT nuclear translocation aggravates ER stress (ERS)-associated apoptosis during H/R injury in neonatal rat cardiomyocytes.Methods:Apoptosis rate and lactate dehydrogenase (LDH) leakage in culture medium were measured as indices of cell injury.Immunofluorescence staining showed the morphological changes of ER and intracellular translocation of CRT.Western blotting or reverse transcription polymerase chain reaction was used to detect the expression of target molecules.Results:Compared with control,H/R increased apoptosis rate and LDH activity.The ER became condensed and bubbled,and CRT translocated to the nucleus.Western blotting showed up-regulation of CRT,Nrf2,activating transcription factor 4 (ATF4),CHOP and caspase-12 expression after H/R.Exogenous CRT overexpression induced by plasmid transfection before H/R increased cell apoptosis,LDH leakage,ER disorder,CRT nuclear translocation and the expression of ERS-associated molecules.However,administration of the ERS inhibitor,taurine,or CRT siRNA alleviated cell injury,ER disorder,and inhibited ERS-associated apoptosis.Conclusions:Our results indicated that during H/R stress,CRT translocation increases cell apoptosis and LDH leakage,aggravates ER disorder,up-regulates expression of nuclear transcription factors,Nrf2 and ATF4,and activates ERS-associated apoptosis.

  7. Diabetes mellitus aggravates hemorrhagic transformation after ischemic stroke via mitochondrial defects leading to endothelial apoptosis.

    Directory of Open Access Journals (Sweden)

    Keisuke Mishiro

    Full Text Available Diabetes is a crucial risk factor for stroke and is associated with increased frequency and poor prognosis. Although endothelial dysfunction is a known contributor of stroke, the underlying mechanisms have not been elucidated. The aim of this study was to elucidate the mechanism by which chronic hyperglycemia may contribute to the worsened prognosis following stroke, especially focusing on mitochondrial alterations. We examined the effect of hyperglycemia on hemorrhagic transformation at 24 hours after middle cerebral artery occlusion (MCAO in streptozotocin (STZ -induced diabetic mice. We also examined the effects of high-glucose exposure for 6 days on cell death, mitochondrial functions and morphology in human brain microvascular endothelial cells (HBMVECs or human endothelial cells derived from induced pluripotent stem cells (iCell endothelial cells. Hyperglycemia aggravated hemorrhagic transformation, but not infarction following stroke. High-glucose exposure increased apoptosis, capase-3 activity, and release of apoptosis inducing factor (AIF and cytochrome c in HBMVECs as well as affected mitochondrial functions (decreased cell proliferation, ATP contents, mitochondrial membrane potential, and increased matrix metalloproteinase (MMP-9 activity, but not reactive oxygen species production. Furthermore, morphological aberration of mitochondria was observed in diabetic cells (a great deal of fragmentation, vacuolation, and cristae disruption. A similar phenomena were seen also in iCell endothelial cells. In conclusion, chronic hyperglycemia aggravated hemorrhagic transformation after stroke through mitochondrial dysfunction and morphological alteration, partially via MMP-9 activation, leading to caspase-dependent apoptosis of endothelial cells of diabetic mice. Mitochondria-targeting therapy may be a clinically innovative therapeutic strategy for diabetic complications in the future.

  8. Coffee and liver health.

    Science.gov (United States)

    Morisco, Filomena; Lembo, Vincenzo; Mazzone, Giovanna; Camera, Silvia; Caporaso, Nicola

    2014-01-01

    Coffee is one of the most widely used beverages in the world. It includes a wide array of components that can have potential implications for health. Several epidemiological studies associate coffee consumption with a reduced incidence of various chronic diseases such as diabetes, cardiovascular diseases, and neurodegenerative diseases. Over the past 20 years, an increasing number of epidemiological and experimental studies have demonstrated the positive effects of coffee on chronic liver diseases. Coffee consumption has been inversely associated with the activity of liver enzymes in subjects at risk, including heavy drinkers. Coffee favours an improvement in hepatic steatosis and fibrosis, and a reduction in cirrhosis and the risk of hepatocellular carcinoma. The mechanisms of action through which it exerts its beneficial effects are not fully understood. Experimental studies show that coffee consumption reduces fat accumulation and collagen deposition in the liver and promotes antioxidant capacity through an increase in glutathione as well as modulation of the gene and protein expression of several inflammatory mediators. Animal and in vitro studies indicate that cafestol and kahweol, 2 diterpens, can operate by modulating multiple enzymes involved in the detoxification process of carcinogens causing hepatocellular carcinoma. It is unclear whether the benefits are significant enough to "treat" patients with chronic liver disease. While we await clarification, moderate daily unsweetened coffee use is a reasonable adjuvant to therapy for these patients.

  9. Immunization with a tetramer derivative of an anti-inflammatory pentapeptide produced by Entamoeba histolytica protects gerbils (Meriones unguiculatus) against experimental amoebic abscess of the liver.

    Science.gov (United States)

    Giménez-Scherer, Juan Antonio; Cárdenas, Guadalupe; López-Osuna, Martha; Velázquez, Juan Raymundo; Rico, Guadalupe; Isibasi, Armando; Maldonado, María del Carmen; Morales, María Esther; Fernández-Diez, Jorge; Kretschmer, Roberto R

    2004-01-01

    Axenically grown Entamoeba histolytica produces a pentapeptide (Met-Gln-Cys-Asn-Ser) with several anti-inflammatory properties, including the inhibition of human monocyte locomotion (Monocyte Locomotion Inhibitory Factor (MLIF)). A construct displays the same effects as the native material. It remains to be seen if MLIF is used, or even produced in vivo by the tissue-invading parasite. If MLIF were to be relevant in invasive amoebiasis, immunizing against it could diminish this parasite advantage and prevent lesions. KLH-linked MLIF mixed with Freund's adjuvant was too aggressive an immunizing material to answer this question. However, immunization with a tetramer of MLIF (but not a scrambled version of MLIF) around a lysine core (MLIF-MAPS), that displays increased antigenicity, yet lacks excessive innate immunity activation, completely protects gerbils against amoebic abscess of the liver caused by the intraportal injection of virulent E. histolytica. Liver abscesses caused by Listeria monocytogenes were not prevented. Invasive E. histolytica may produce the parent protein of MLIF in vivo, and if appropriately cleaved, it may play a role in invasive amoebiasis. MLIF may join new vaccination strategies against amoebiasis.

  10. A Critical Evaluation of Liver Pathology in Humans with Danon Disease and Experimental Correlates in a Rat Model of LAMP-2 Deficiency.

    Science.gov (United States)

    Wang, Lu; Wang, Jingbo; Cai, Weile; Shi, Yongquan; Zhou, Xinmin; Guo, Guanya; Guo, Changcun; Huang, Xiaofeng; Han, Zheyi; Zhang, Shuai; Ma, Shuoyi; Zhou, Xia; Fan, Daiming; Eric Gershwin, M; Han, Ying

    2017-01-26

    Danon disease is a genetic deficiency in lysosome-associated membrane protein 2 (LAMP-2), a highly glycosylated constituent of the lysosomal membrane and characterized by a cardiomyopathy, skeletal muscle myopathy, and cognitive impairment. Patients, however, often manifest hepatic abnormalities, but liver function has not been well evaluated and the syndrome is relatively uncommon. Hence, we have taken advantage of a rat that has been deleted of LAMP-2 to study the relative role of LAMP-2 on liver function. Interestingly, rats deficient in LAMP-2 develop a striking increase in serum alkaline phosphatase (ALP) and a decrease in bile flow compared with wild-type littermates. Importantly and by ultrastructural analysis, deficient rats manifest dilated canaliculi that lack microvilli with evidence of bile-containing bodies. Moreover, following bile duct ligation, LAMP-2-deficient rats develop rapid and severe evidence of advanced cholestasis, with an increase in serum bilirubin, as early as 6 h later. In wild-type control rats, multidrug resistance-associated protein 2 (Mrp2) normally concentrates at the bile canalicular membranes to secrete conjugated bilirubin into bile. However, in LAMP-2(y/-) rats, Mrp2 was detected in hepatocytes compared with other canalicular proteins including P-glycoproteins, dipeptidyl peptidase IV (CD26), and aminopeptidase (CD13). Our data further suggest that LAMP-2 interacts with the membrane cytoskeletal proteins radixin and F-actin in determining the localization of integral membrane proteins.

  11. Effects of interleukin-18 and Anti-interleukin-18-mAb on Experimental immunological Liver Fibrosis induced by Repeatedly Administered Concanavalin A and its Mechanism

    Institute of Scientific and Technical Information of China (English)

    You-wen Tan; Jian-cheng Wu; Yun Ye; Li Chen; Peng-li Pai

    2014-01-01

    Objective To explore the prevention of IL-18 or anti-IL-18-mAb to the immune liver fibrosis model induced by repeated injection of concanavalin A in BALB/c mice and its mechanism. Methods Total of 120 BALB/c mice were divided into four groups, control group mice (Ga) were injected weekly with normal saline, concanavalin A group was divided into Gb, Gc, Gd. All mice were injected with concanavalin A (15 mg/kg) once a week. Moreover, Gc, Gd mice were injected weekly with IL-18 (7.5 mg/kg) and anti-IL-18-mAb (10 mg/kg) 2 hours before treatment with concanavalin A, respectively. Twenty-four hours after concanavalin A challenge at 1, 5, 12 and 20 weeks, 3 mice were killed by vena orbitalis, repectively. The sera were storaged at 4℃for detecting of up TNF-αand IFN-γby ELISA. The liver of mice in different groups were excised and fixed in 10%formalin for HE staining and Masson staining or frozen in liquid nitrogen for immunohistochemical staining forα-SMA. After extracting of total RNA from liver tissue, MMP-2 and TIMP-1 A messenger RNA were amplified by reverse transcription polymerase chain reaction (PCR). Products were electrophoresed on agrose gel containing ethidium bromide and visualized under ultraviolet light. Densitometric RT-PCR data were standardized withβ-actin signals. Results After experiment, the number of dead mice of Ga, Gb, Gc and Gd were 0, 6, 15 and 3, respectively. There were significant difference on each group (P<0.05). At the fifth week of experiment, hepatocellular necrosis in IL-18 administered group mice had become widespread throughout the lobule. Evidence of liver fibrosis was observed during this period. However, at the twelfth week of experimemt, bridging fibrosis and large fibrosis strip in the parenchyma with hepatocellular necrosis was detectable in Gb, but at twentieth week, only the small fibrosis strip had been found in anti-IL-18-mAb administered group mice by HE staining and Masson staining. The serum levels of TNF-αand IFN

  12. Oxidative stress and endothelial function in chickens with experimental fatty liver hemorrhagic syndrome%试验性脂肪肝出血综合征鸡氧化应激水平和内皮功能变化

    Institute of Scientific and Technical Information of China (English)

    姜锦鹏; 顾有方; 吕锦芳; 宁康健; 应如海; 胡忠泽; 李静

    2013-01-01

    The present study aimed to explore the relationship between oxidative stress and endothelial function in chickens with fatty liver hemorrhagic syndrome (FLHS). Three hundred twenty 14 day-old cyan-shank partridge chickens were divided randomly to 4 treatment groups with 4 replications of 20 each,including control (C),high-fat diet (HF),estrogen-injected (E),high fat diet plus estrogen-injected (HF+E). The experimental period lasted from 15 to 42 day-old. Hepatic histopathology and biochemical parameters related to liver oxidative stress, liver function and endothelial function were determined at 14 d interval. The results showed as following: (1) the chickens in model groups displayed severe impairment of liver histology (increased liver total lipids,hepatic steatosis and liver hemorrhage) reproducing typical histological features of chicken FLHS; (2) compared with the control group, the contents of malondialdehyde (MDA) (P<0. 05) in liver and angiotensin Ⅱ (AngⅡ ) in plasma were increased, whereas the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in liver and the contents of serum nitric oxide (NO) were decreased in model groups on day 14 and 28;(3) hepatic steatosis was positively correlated with MDA (r=0. 949, P<0. 01), and negatively correlated with SOD (r=-0. 864, P <0. 01) and GSH-Px (r= -0. 897,P<0. 01). MDA was positively correlated with liver hemorrhage score (r=0. 859, P<0. 01) and plasma Ang Ⅱ (r = 0. 902, P<0. 01). Activity of SOD or GSH-Px in liver was inversely correlated with liver hemorrhage score (r=-0. 901,P<0. 01 or r= -0. 760,P<0. 05) and positively correlated with NO (r=0. 714, P<0. 05 or r=0. 734, P< 0. 05). Plasma levels of Ang H were positively correlated with liver hemorrhage score (r=0. 784,P <0. 05). The trial shows that excessive oxidative stress is involved,at least in part,in endothelial dysfunction and the mechanism of vascular injury may be mediated by oxidative stress and

  13. [Biochemical parameters of blood and morpho-functional state of the liver of experimental animals by the actions of lead sulfide nanoparticles in different time study].

    Science.gov (United States)

    Omel'chuk, S T; Aleksiĭchuk, V D; Sokurenko, L M

    2014-01-01

    Biochemical studies revealed that alanine aminotransferase levels changing first during short action (30 injections) of lead sulfide nanoparticles of size 10 and 30 nm, and the ionic form of a 400 nm lead while the growth of both enzymes (aspartate aminotransferase and alanine aminotransferase) activity during long-term exposure (60 injections) is the same intensity. It it confirmed by the value of de Ritis coefficient, which is statistically the same as control. Morphological studies also confirm these data--degenerative changes of hepatocytes, reactive changes of the stroma and vascular responses were detected. It is shown that the severity of metabolic and morphological damages in the liver increased with prolonging the duration of lead nanoparticles intake.

  14. Evaluation of local immune response to Fasciola hepatica experimental infection in the liver and hepatic lymph nodes of goats immunized with Sm14 vaccine antigen

    Directory of Open Access Journals (Sweden)

    Ricardo E Mendes

    2010-08-01

    Full Text Available Protection against Fasciola hepatica in goats immunized with a synthetic recombinant antigen from Schistosoma mansoni fatty acid-binding protein 14 (rSm14 was investigated by assessing worm burdens, serum levels of hepatic enzymes, faecal egg count and hepatic damage, which was evaluated using gross and microscopic morphometric observation. The nature of the local immune response was assessed by examining the distribution of CD2+, CD4+, CD8+ and γ´+ T lymphocytes along with IgG+, IL-4+ and IFN-γ+ cells in the liver and hepatic lymph nodes (HLN. The goats used consisted of group 1 (unimmunized and uninfected, group 2 [infected control - immunized with Quillaia A (Quil A] and group 3 (immunized with rSm14 in Quil A and infected, each containing seven animals. Immunization with rSm14 in Quil A adjuvant induced a reduction in gross hepatic lesions of 56.6% (p < 0.001 and reduced hepatic and HLN infiltration of CD2+, CD4+, CD8+ and γ´+ T lymphocytes as well as IL-4+ and IFN-γ+ cells (p < 0.05. This is the first report of caprine immunization against F. hepatica using a complete rSm14 molecule derived from S. mansoni. Immunization reduced hepatic damage and local inflammatory infiltration into the liver and HLN. However, considering that Quil A is not the preferential/first choice adjuvant for Sm14 immunization, further studies will be undertaken using the monophosphoryl lipid A-based family of adjuvants during clinical trials to facilitate anti-Fasciolavaccine development.

  15. Boron neutron capture therapy (BNCT) for liver metastasis in an experimental model: dose–response at five-week follow-up based on retrospective dose assessment in individual rats

    Energy Technology Data Exchange (ETDEWEB)

    Emiliano C. C. Pozzi; Veronica A. Trivilin; Lucas L. Colombo; Andrea Monti Hughes; Silvia I. Thorp; Jorge E. Cardoso; Marcel A. Garabalino; Ana J. Molinari; Elisa M. Heber; Paula Curotto; Marcelo Miller; Maria E. Itoiz; Romina F. Aromando; David W. Nigg; Amanda E. Schwint

    2013-11-01

    Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. Employing an experimental model of liver metastases in rats, we recently demonstrated that BNCT mediated by boronophenylalanine (BPA-BNCT) at 13 Gy prescribed to tumor is therapeutically useful at 3-week follow-up. The aim of the present study was to evaluate dose–response at 5-week follow-up, based on retrospective dose assessment in individual rats. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA-BNCT (n = 19), Beam only (n = 8) and Sham (n = 7) (matched manipulation, no treatment). For each rat, neutron flux was measured in situ and boron content was measured in a pre-irradiation blood sample for retrospective individual dose assessment. For statistical analysis (ANOVA), individual data for the BPA-BNCT group were pooled according to absorbed tumor dose, BPA-BNCT I: 4.5–8.9 Gy and BPA-BNCT II: 9.2–16 Gy. At 5 weeks post-irradiation, the tumor surface area post-treatment/pre-treatment ratio was 12.2 +/- 6.6 for Sham, 7.8 +/- 4.1 for Beam only, 4.4 +/- 5.6 for BPA-BNCT I and 0.45 +/- 0.20 for BPA-BNCT II; tumor nodule weight was 750 +/- 480 mg for Sham, 960 +/- 620 mg for Beam only, 380 +/- 720 mg for BPA-BNCT I and 7.3 +/- 5.9 mg for BPA-BNCT II. The BPA-BNCT II group exhibited statistically significant tumor control with no contributory liver toxicity. Potential threshold doses for tumor response and significant tumor control were established at 6.1 and 9.2 Gy, respectively.

  16. Effect of inositol requiring enzyme 1-mediated endoplasmic reticulum stress in liver cell apoptosis of experimental fulminant hepatic failure and its significance

    Institute of Scientific and Technical Information of China (English)

    甄真

    2013-01-01

    Objective To study the role of inositol requiring enzyme 1(IRE1)-mediated endoplasmic reticulum stress on hepatocyte apoptosis of experimental fulminant hepatic failure(FHF). Methods Thirty male depuratory Wistar

  17. Effect of lysozyme chloride on betel quid chewing aggravated gastric oxidative stress and hemorrhagic ulcer in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Chen-Road Hung

    2005-01-01

    AIM: To evaluate the protective effect of lysozyme chloride on betel quid chewing (BQC) aggravated gastric oxidative stress and hemorrhagic ulcer in rats with diabetes mellitus (DM).METHODS: Male Wistar rats were challenged intravenously with streptozotocin (65 mg/kg) to induce DM. Rats were fed with regular pellet food or BQC-containing diets. After 90 d, rats were deprived of food for 24 h. Rat stomachs were irrigated for 3 h with normal saline or simulated gastric juice. Rats were killed and gastric specimens were harvested.RESULTS: An enhancement of various gastric ulcerogenic parameters, including acid back-diffusion, mucosal lipid peroxide generation, as well as decreased glutathione levels and mucus content, were observed in DM rats. After feeding DM rats with BQC, an exacerbation of these ulcerogenic parameters was achieved. Gastric juice caused a further aggravation of these ulcerogenic parameters. Daily intragastric lysozyme chloride dose-dependently inhibited exacerbation of various ulcerogenic parameters in those BQC-fed DM rats.CONCLUSION: (1) Gastric juice could aggravate both DM and BQC-fed DM rat hemorrhagic ulcer; (2) BQC exacerbated gastric hemorrhagic ulcer in DM rats via enhancing oxidative stress and reducing defensive factors; (3) lysozyme chloride effectively protected BQC aggravated gastric damage in DM rats.

  18. Aggravation of Risk and Precautionary Measures in Non-Life Insurance: A Tricky Scope for the Insurer?

    Directory of Open Access Journals (Sweden)

    Olavi-Jüri Luik

    2015-12-01

    Full Text Available Aggravation of risk and failure to take precautionary measures are focal issues in non-life insurance in terms of potential partial or full release of the insurer from the duty to perform. Not infrequently, it is difficult to draw a line between the aggravation of risk on the one hand, and non-compliance with precautionary measures on the other, since a particular action by a policyholder may present both situations. At the same time, the legal remedies available to the insurer regarding these two situations are different in scope. The aggravation of risk and non-compliance with precautionary measures are precisely the bases on which insurers actually reduce indemnity or refuse to compensate for damages. This article explores the differences between insurance laws in the Baltic states—specifically, the Estonian Law of Obligations Act, the Latvian Insurance Contract Law and Lithuanian rules contained in the Civil Code and Insurance Law. The article explores the differences between the Baltic states’ insurance laws and the Principles of European Insurance Contract Law (PEICL with regard to a policyholder’s duty in relation to aggravation of risk and precautionary measures, as the rights and obligations of policyholders do change where the optional instrument is applied. The article also includes comparisons to German, Finnish and Russian insurance law.

  19. Contributions of Streptococcus mutans Cnm and PA antigens to aggravation of non-alcoholic steatohepatitis in mice

    Science.gov (United States)

    Naka, Shuhei; Hatakeyama, Rina; Takashima, Yukiko; Matsumoto-Nakano, Michiyo; Nomura, Ryota; Nakano, Kazuhiko

    2016-01-01

    Streptococcus mutans, a major pathogen of dental caries, can cause infective endocarditis after invading the bloodstream. Recently, intravenous administration of specific S. mutans strains was shown to aggravate non-alcoholic steatohepatitis (NASH) in a mouse model fed a high-fat diet. Here, we investigated the mechanism of this aggravation in a NASH mouse model by focusing on the S. mutans cell surface collagen-binding protein (Cnm) and the 190-kDa protein antigen (PA). Mice that were intravenously administered a S. mutans strain with a defect in Cnm (TW871CND) or PA (TW871PD) did not show clinical or histopathological signs of NASH aggravation, in contrast to those administered the parent strain TW871. The immunochemical analyses demonstrated higher levels of interferon-γ and metallothionein expression in the TW871 group than in the TW871CND and TW871PD groups. Analysis of bacterial affinity to cultured hepatic cells in the presence of unsaturated fatty acids revealed that the incorporation rate of TW871 was significantly higher than those of TW871CND and TW871PD. Together, our results suggest that Cnm and PA are important cell surface proteins for the NASH aggravation caused by S. mutans adhesion and affinity for hepatic cells. PMID:27833139

  20. 新风胶囊肝肾亚急性毒性实验研究%Experimental study on liver and kidney subacute toxicity induced by Xinfeng capsules

    Institute of Scientific and Technical Information of China (English)

    成遥; 张贺; 孟楣; 刘健

    2015-01-01

    Objecetive To study the hepatotoxicity and nephrotoxicity in rats induced by Xinfeng capsules(XFC),toprovide expremen-tal evidence for clinical rational medication.Methods 60 SD rats were randomized into 5 groups:the tripterygium wilfordii group,the high dose(of XFC)group,the middle dose(of XFC)group,the low dose(of XFC)group and the normal group,all of which were treated with intragastric injection administration for 30 days.After the last administration,rats were disposed to return the serum ,liver and kid-ney tissues.Using the fully automatic biochemical analyser to detect the related function indicators (e.g.,ALT,AST,BUN,SCr),and observe the pathology change and the transformation of the liver and kidney tissues.Results Thebiochemical Indicatorsresults,After 30 daysALT,AST,BUN,SCr levels in the tripterygium wilfordii group were significantly enhanced(P 0.05).Pathologicalchangeresults:The tripterygium wilfordii group:liver kidney tissues were slightly swelling,and a few inflammatory cells infiltration and other pathological injuries were also observed,XFC group have no significant change either.These in-juries were more severe than groups of different dose levels of XFC.Conclusions XFC can significantly reduce the hepatotoxicity and-nephrotoxicityinduced by the tripterygiumwilfordii,thatcan beusedin clinical safely,but the detoxification is still unclear now,which-needs further study.%目的:考察新风胶囊(XFC)对大鼠肝、肾的亚急性毒性影响,为临床合理用药提供实验依据。方法60只 SD 大鼠分为雷公藤给药组、XFC 给药组(低、中、高)、空白组5个组,每组12只,给大鼠连续灌胃30 d。取大鼠的血清及肝、肾组织,观察肝、肾形态改变。由全自动生化仪检测相关肝、肾功能指标包括血清谷丙转氨酸(ALT)、谷草转氨酸(AST)、尿素氮(BUN)、血肌酐(SCr)。大鼠肝肾组织 HE 染色后,观察其病理改变。结果生化指标结

  1. Neuronal chloride accumulation and excitatory GABA underlie aggravation of neonatal epileptiform activities by phenobarbital.

    Science.gov (United States)

    Nardou, Romain; Yamamoto, Sumii; Chazal, Geneviève; Bhar, Asma; Ferrand, Nadine; Dulac, Olivier; Ben-Ari, Yehezkel; Khalilov, Ilgam

    2011-04-01

    Phenobarbital produces its anti-epileptic actions by increasing the inhibitory drive of γ-aminobutyric acid. However, following recurrent seizures, γ-aminobutyric acid excites neurons because of a persistent increase of chloride raising the important issue of whether phenobarbital could aggravate persistent seizures. Here we compared the actions of phenobarbital on initial and established ictal-like events in an in vitro model of mirror focus. Using the in vitro three-compartment chamber preparation with the two hippocampi and their commissural fibres placed in three different chambers, kainate was applied to one hippocampus and phenobarbital contralaterally, either after one ictal-like event or after many recurrent ictal-like events that produce an epileptogenic mirror focus. Field, perforated patch and single-channel recordings were used to determine the effects of γ-aminobutyric acid and their modulation by phenobarbital, and alterations of the chloride cotransporters were investigated using sodium-potassium-chloride cotransporter 1 and potassium chloride cotransporter 2 antagonists, potassium chloride cotransporter 2 immunocytochemistry and sodium-potassium-chloride cotransporter 1 knockouts. Phenobarbital reduced initial ictal-like events and prevented the formation of a mirror focus when applied from the start. In contrast, phenobarbital aggravated epileptiform activities when applied after many ictal-like events by enhancing the excitatory actions of γ-aminobutyric acid due to increased chloride. The accumulation of chloride and the excitatory actions of γ-aminobutyric acid in mirror foci neurons are mediated by the sodium-potassium-chloride cotransporter 1 chloride importer and by downregulation and internalization of the chloride-exporter potassium-chloride cotransporter 2. Finally, concomitant applications of the sodium-potassium-chloride cotransporter 1 antagonist bumetanide and phenobarbital decreased excitatory actions of γ-aminobutyric acid and

  2. Liver Function Tests

    Science.gov (United States)

    ... Baby Boomers Get Tested Core Programs HE Webinar Disney 2014 5 Ways to Love Your Liver Liver ... Drive Away Liver Disease Liver Lowdown Aug 2013 Disney Marathon In The Field Healthy Foods Diet Recommendations ...

  3. Benign Liver Tumors

    Science.gov (United States)

    ... Baby Boomers Get Tested Core Programs HE Webinar Disney 2014 5 Ways to Love Your Liver Liver ... Drive Away Liver Disease Liver Lowdown Aug 2013 Disney Marathon In The Field Healthy Foods Diet Recommendations ...

  4. Liver cancer - hepatocellular carcinoma

    Science.gov (United States)

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or ...

  5. Liver Transplant: Nutrition

    Science.gov (United States)

    ... ZIP code here Enter ZIP code here Liver Transplant: Nutrition for Veterans and the Public Nutrition Liver ... apply to transplant and liver disease patients. Pre-Transplant Protein Malnutrition -- Many patients with end stage liver ...

  6. Elevated Liver Enzymes

    Science.gov (United States)

    Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

  7. Angiogenesis and liver fibrosis

    Institute of Scientific and Technical Information of China (English)

    Gülsüm ?zlem Elpek

    2015-01-01

    Recent data indicate that hepatic angiogenesis,regardless of the etiology, takes place in chronic liverdiseases (CLDs) that are characterized by inflammationand progressive fibrosis. Because antiangiogenictherapy has been found to be efficient inthe prevention of fibrosis in experimental models ofCLDs, it is suggested that blocking angiogenesis couldbe a promising therapeutic option in patients withadvanced fibrosis. Consequently, efforts are beingdirected to revealing the mechanisms involved inangiogenesis during the progression of liver fibrosis.Literature evidences indicate that hepatic angiogenesisand fibrosis are closely related in both clinical andexperimental conditions. Hypoxia is a major inducer ofangiogenesis together with inflammation and hepaticstellate cells. These profibrogenic cells stand at theintersection between inflammation, angiogenesis andfibrosis and play also a pivotal role in angiogenesis.This review mainly focuses to give a clear view on therelevant features that communicate angiogenesis withprogression of fibrosis in CLDs towards the-end point ofcirrhosis that may be translated into future therapies.The pathogenesis of hepatic angiogenesis associatedwith portal hypertension, viral hepatitis, non-alcoholicfatty liver disease and alcoholic liver disease are alsodiscussed to emphasize the various mechanisms involvedin angiogenesis during liver fibrogenesis.

  8. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008447 Identification of gene expression patterns in a rat model of nonalcoholic fatty liver disease. ZHANG Xuequn(张雪群), et al. Dept Gastroenterol, 1st Hosp, Med Coll, Zhejiang Univ, Hangzhou 310003. Chin J Dig 2008;28(5):323-327. Objective To compare and analyze gene expression patterns in a rat model of nonalcoholic fatty liver disease (NAFLD). Methods Twelve male Sprague-Dawley rats were randomly given either general diet (control group) or a high-fat diet (model group) for 4 weeks.

  9. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008310 Expression of αVβ3 integrin and platelet-endothelial cell adhesion molecule-1 in progressive liver fibrosis: experiment with rats. SONG Zhengji(宋正已), et al. Dept Gastroenterol, Zhongshan Hosp, Fudan Univ, Shanghai 200032. Natl Med J China 2008;88(16):1121-1125.Objective To investigate the expression ofαVβ3 integrin and platelet endothelial cell adhesion molecule-1(CD31)in progressive liver fibrosis of rats.Methods Sixty-four SD rats were randomly divided into 4 equal groups:TAA group,undergoing peritoneal injection of

  10. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008075 Effect of Jiangzhi granules on expression of leptin receptor mRNA, P-JAK2 and P-STAT3 in rats with non-alcoholic fatty liver disease. MA Zansong(马赞颂), et al. Dept Gastroenterol, Instit Spleen and Stomach Dis, Longhua Hosp. Shanghai TCM Univ, Shanghai 200032.World Chin J Digestol 2007;15(32):3360-3366. Objective To study the effect of Jiangzhi granules on non-alcoholic fatty liver disease in rats, and on the expression of

  11. Results of radiation therapy for primary liver cancer. Long-term influence of irradiation on liver function

    Energy Technology Data Exchange (ETDEWEB)

    Wadasaki, Kouichi; Kimura, Fumi; Oomae, Tadayuki; Urashima, Masaki; Mori, Masaki [Hiroshima Atomic Bomb Hospital (Japan)

    1995-06-01

    During the period from June 1991 through May 1993, 6 patients (3 males and 3 females) were treated with radiation therapy of 60 Gy or more for hepatomas complicated with liver cirrhosis type C. They ranged in age from 62 to 76 years with a mean of 70. Tumor size was examined on CT before and 2 months after irradiation. In addition, changes in liver function following irradiation were examined. In 4 of the 6 patients, tumor decreased by 27-90% at 11 to 43 months after irradiation. Although liver function was irreversibly aggravated in one patient, it was slight and recovered 6 months after irradiation in the other 5 patients. High dose irradiation to the limited fields is considered useful in the treatment of hepatoma. (S.Y.).

  12. Bacteriophage Administration Reduces the Concentration of Listeria monocytogenes in the Gastrointestinal Tract and Its Translocation to Spleen and Liver in Experimentally Infected Mice

    Directory of Open Access Journals (Sweden)

    Volker Mai

    2010-01-01

    Full Text Available To investigate the efficacy of phage supplementation in reducing pathogen numbers, mice were treated via oral gavage with a Listeria monocytogenes phage preparation (designated ListShield before being orally infected with L. monocytogenes. The concentrations of L. monocytogenes in the liver, spleen, and intestines were significantly lower (P<.05 in the phage-treated than in the control mice. Phage and antibiotic treatments were similarly effective in reducing the levels of L. monocytogenes in the internal organs of the infected mice. However, the significant weight loss detected in the control and antibiotic-treated groups was not observed in the infected, ListShield-treated mice. Long-term (90 days, biweekly treatment of uninfected mice with ListShield did not elicit detectable changes in the microbiota of their large intestines or deleterious changes in their health. Our data support the potential feasibility of using bacteriophages to control proliferation of L. monocytogenes in mice without affecting commensal microbiota composition.

  13. Antitumor magnetic hyperthermia induced by RGD-functionalized Fe3O4 nanoparticles, in an experimental model of colorectal liver metastases

    Directory of Open Access Journals (Sweden)

    Oihane K. Arriortua

    2016-10-01

    Full Text Available This work reports important advances in the study of magnetic nanoparticles (MNPs related to their application in different research fields such as magnetic hyperthermia. Nanotherapy based on targeted nanoparticles could become an attractive alternative to conventional oncologic treatments as it allows a local heating in tumoral surroundings without damage to healthy tissue. RGD-peptide-conjugated MNPs have been designed to specifically target αVβ3 receptor-expressing cancer cells, being bound the RGD peptides by “click chemistry” due to its selectivity and applicability. The thermal decomposition of iron metallo-organic precursors yield homogeneous Fe3O4 nanoparticles that have been properly functionalized with RGD peptides, and the preparation of magnetic fluids has been achieved. The nanoparticles were characterized by transmission electron microscopy (TEM, vibrating sample magnetometry (VSM, electron magnetic resonance (EMR spectroscopy and magnetic hyperthermia. The nanoparticles present superparamagnetic behavior with very high magnetization values, which yield hyperthermia values above 500 W/g for magnetic fluids. These fluids have been administrated to rats, but instead of injecting MNP fluid directly into liver tumors, intravascular administration of MNPs in animals with induced colorectal tumors has been performed. Afterwards the animals were exposed to an alternating magnetic field in order to achieve hyperthermia. The evolution of an in vivo model has been described, resulting in a significant reduction in tumor viability.

  14. Aging and its impact onthe quality of grafts: an experimental study in rats livers O impacto do envelhecimento na qualidade do enxerto: estudo experimental em fígados de ratos

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    Stela Maria Mota

    2010-09-01

    Full Text Available CONTEXT: There are consistent clues of worse results with grafts from older donors, especially in hepatitis C. University of Wisconsin (UW solution is adopted for liver preservation, but other solutions are being studied, as fructose-1,6-bisphosphate (FBP. OBJECTIVE: To determinate the impact of aging of the donor on the cold ischemia injury in rat livers and compare UW and FBP. METHODS: Twenty male Wistar rats were studied - 10, aging 20 weeks: 5 to preservation with UW (C-UW and 5, FBP (C-FBP; and other 10, aging 50 weeks: 5 to UW (E-UW and 5 to FBP (E-FBP. Rats were anesthesized, submitted to hepatectomy, and graft was kept under 2-4ºC for 8 hours. Liquid samples were taken at 2, 4, 6, and 8 hours, to determine AST and LDH. At the end, in the liver tissue thiobarbituric acid reactive substances and catalase were determined. RESULTS: Average liver weight was similar between controls and the others (12.5 g ± 1.8 and 13.4 g ± 2.0. AST and LDH levels were higher in C-UW group (PCONTEXTO: Dados da literatura atual sugerem piores resultados quando os transplantes hepáticos são realizados com enxertos provenientes de doadores idosos. O uso da solução Universidade de Wisconsin (UW é universal; entretanto alternativas como a fructose-1,6-bisfosfato (FBP vêm sendo estudadas. OBJETIVOS: Determinar o impacto do envelhecimento do doador no dano de isquemia a frio em fígados de ratos, comparando as soluções de FBP e UW. MÉTODOS: Vinte ratos Wistar foram estudados - 10 com 20 semanas: 5 preservados com UW (C-UW e 5 com FBP (C-FBP; e outros 10, com 50 semanas: 5 com UW (E-UW e 5 com FBP (E-FBP. A preservação durou 8 horas. Foram dosadas AST e LDH nas alíquotas do líquido de preservação a cada 2 horas. RESULTADOS: Os níveis de AST e LDH foram superiores no grupo (C-UW (P<0.05. Quando comparadas UW x FBP no grupo de idosos houve diferença quanto à LDH, mas não com a AST. CONCLUSÃO: A preservação dos fígados de ratos idosos foi

  15. The efficacy of an ivermectin/closantel injection against experimentally induced infections and field infections with gastrointestinal nematodes and liver fluke in cattle

    NARCIS (Netherlands)

    Borgsteede, F.H.M.; Taylor, S.; Gaasenbeek, C.P.H.; Couper, A.; Cromie, L.

    2008-01-01

    Three studies were performed to test the efficacy of an ivermectin/closantel injection (200 ¿g/kg¿1 ivermectin and 5 mg/kg¿1 closantel) in cattle. Two were experimentally induced infections of Ostertagia ostertagi, Cooperia oncophora and Fasciola hepatica in calves, and the third had natural field i

  16. ERK5 knock down aggravates detrimental effects of hypothermal stimulation on cardiomyocytes via Bim upregulation.

    Science.gov (United States)

    Wang, Yao-Sheng; Zhou, Jing; Liang, Chun; Hong, Kui; Cheng, Xiao-Shu; Wu, Zong-Gui

    2013-09-01

    Mechanism of cold induced myocardial injury remained unclear. Our study investigated the role of ERK5/Bim pathway in hypothermal stimulation-induced apoptosis or damage of cardiomyocytes (CMs). Results showed that in CMs which under hypothermal stimulation, ERK5 siRNA promoted expression of Bim protein. Bim siRNA did not influence ERK5 expression but attenuated production of p-ERK5. ERK5 siRNA induced higher apoptosis rate; intracellular Ca(2+) overload; ROS activity; ΔΨm damage in hypothermia stimulated CMs, when compared with hypothermal stimulation solely treated group, while Bim siRNA effected oppositely and canceled pro-apoptotic effect of ERK5 siRNA. In conclusion, ERK5 knock down releases inhibition to Bim expression, induces aggravated apoptosis in CMs under hypothermal stimulation, which related to higher intracellular Ca(2+) overload, ROS activity, and more severe ΔΨm damage. Results revealed regulative role of ERK5/Bim pathway in hypothermal stimulation-induced injure or apoptosis of cardiomyocytes.

  17. Nlrp3-inflammasome activation in non-myeloid-derived cells aggravates diabetic nephropathy.

    Science.gov (United States)

    Shahzad, Khurrum; Bock, Fabian; Dong, Wei; Wang, Hongjie; Kopf, Stefan; Kohli, Shrey; Al-Dabet, Moh'd Mohanad; Ranjan, Satish; Wolter, Juliane; Wacker, Christian; Biemann, Ronald; Stoyanov, Stoyan; Reymann, Klaus; Söderkvist, Peter; Groß, Olaf; Schwenger, Vedat; Pahernik, Sascha; Nawroth, Peter P; Gröne, Herman-Josef; Madhusudhan, Thati; Isermann, Berend

    2015-01-01

    Diabetic nephropathy is a growing health concern with characteristic sterile inflammation. As the underlying mechanisms of this inflammation remain poorly defined, specific therapies targeting sterile inflammation in diabetic nephropathy are lacking. Intriguingly, an association of diabetic nephropathy with inflammasome activation has recently been shown, but the pathophysiological relevance of this finding remains unknown. Within glomeruli, inflammasome activation was detected in endothelial cells and podocytes in diabetic humans and mice and in glucose-stressed glomerular endothelial cells and podocytes in vitro. Abolishing Nlrp3 or caspase-1 expression in bone marrow-derived cells fails to protect mice against diabetic nephropathy. Conversely, Nlrp3-deficient mice are protected against diabetic nephropathy despite transplantation of wild-type bone marrow. Pharmacological IL-1R antagonism prevented or even reversed diabetic nephropathy in mice. Mitochondrial reactive oxygen species (ROS) activate the Nlrp3 inflammasome in glucose or advanced glycation end product stressed podocytes. Inhibition of mitochondrial ROS prevents glomerular inflammasome activation and nephropathy in diabetic mice. Thus, mitochondrial ROS and Nlrp3-inflammasome activation in non-myeloid-derived cells aggravate diabetic nephropathy. Targeting the inflammasome may be a potential therapeutic approach to diabetic nephropathy.

  18. Carbon monoxide pollution aggravates ischemic heart failure through oxidative stress pathway

    Science.gov (United States)

    Reboul, Cyril; Boissière, Julien; André, Lucas; Meyer, Gregory; Bideaux, Patrice; Fouret, Gilles; Feillet-Coudray, Christine; Obert, Philippe; Lacampagne, Alain; Thireau, Jérôme; Cazorla, Olivier; Richard, Sylvain

    2017-01-01

    Risk of hospital readmission and cardiac mortality increases with atmospheric pollution for patients with heart failure. The underlying mechanisms are unclear. Carbon monoxide (CO) a ubiquitous environmental pollutant could be involved. We explored the effect of daily exposure of CO relevant to urban pollution on post-myocardial infarcted animals. Rats with ischemic heart failure were exposed 4 weeks to daily peaks of CO mimicking urban exposure or to standard filtered air. CO exposure worsened cardiac contractile dysfunction evaluated by echocardiography and at the cardiomyocyte level. In line with clinical reports, the animals exposed to CO also exhibited a severe arrhythmogenic phenotype with numerous sustained ventricular tachycardias as monitored by surface telemetric electrocardiograms. CO did not affect cardiac β–adrenergic responsiveness. Instead, mitochondrial dysfunction was exacerbated leading to additional oxidative stress and Ca2+ cycling alterations. This was reversed following acute antioxidant treatment of cardiomyocytes with N-acetylcysteine confirming involvement of CO-induced oxidative stress. Exposure to daily peaks of CO pollution aggravated cardiac dysfunction in rats with ischemic heart failure by specifically targeting mitochondria and generating ROS-dependent alterations. This pathway may contribute to the high sensibility and vulnerability of individuals with cardiac disease to environmental outdoor air quality. PMID:28045070

  19. Glucocorticoids aggravate retrograde memory deficiency associated with traumatic brain injury in rats.

    Science.gov (United States)

    Chen, Xin; Zhang, Ke-Li; Yang, Shu-Yuan; Dong, Jing-Fei; Zhang, Jian-Ning

    2009-02-11

    Administration of glucocorticoid to patients with head injury has previously been demonstrated to impair memory. We hypothesize that glucocorticoids promote post-traumatic hippocampal apoptosis, resulting in retrograde memory deficiency associated with traumatic brain injury (TBI). In the present study, we tested this hypothesis by measuring spatial memory deficiency in rats subjected to fluid percussion injury (FPI) and receiving dexamethasone (DXM at 0.5-10 mg/kg) or methylprednisolone (MP at 5-30 mg/kg); we also examined neuronal apoptosis in hippocampus. Adult male Wistar rats were trained for the acquisition of spatial memory, then subjected to FPI and tested for spatial reference memory on post-injury days 7 and 14 using the Morris Water Maze. Brain tissue from injured rats was examined 24 h to 2 weeks after injury. The percent time in the goal quadrant, which measures spatial reference memory, was significantly lower in injured rats receiving either high-dose DXM or MP than in control groups. TUNEL-positive cells in hippocampus were first detected 24 h post-injury, plateauing at 48h. The number of TUNEL-positive cells was significantly higher in injured rats treated with either DXM or MP. The data suggest that glucocorticoid therapy for TBI may increase neuronal apoptosis in hippocampus and, as a result, aggravate retrograde memory deficits induced by TBI.

  20. Absence of intestinal PPARγ aggravates acute infectious colitis in mice through a lipocalin-2-dependent pathway.

    Directory of Open Access Journals (Sweden)

    Parag Kundu

    2014-01-01

    Full Text Available To be able to colonize its host, invading Salmonella enterica serovar Typhimurium must disrupt and severely affect host-microbiome homeostasis. Here we report that S. Typhimurium induces acute infectious colitis by inhibiting peroxisome proliferator-activated receptor gamma (PPARγ expression in intestinal epithelial cells. Interestingly, this PPARγ down-regulation by S. Typhimurium is independent of TLR-4 signaling but triggers a marked elevation of host innate immune response genes, including that encoding the antimicrobial peptide lipocalin-2 (Lcn2. Accumulation of Lcn2 stabilizes the metalloproteinase MMP-9 via extracellular binding, which further aggravates the colitis. Remarkably, when exposed to S. Typhimurium, Lcn2-null mice exhibited a drastic reduction of the colitis and remained protected even at later stages of infection. Our data suggest a mechanism in which S. Typhimurium hijacks the control of host immune response genes such as those encoding PPARγ and Lcn2 to acquire residence in a host, which by evolution has established a symbiotic relation with its microbiome community to prevent pathogen invasion.

  1. Cedar Pollen Aggravates Atopic Dermatitis in Childhood Monozygotic Twin Patients with Allergic Rhino Conjunctivitis

    Directory of Open Access Journals (Sweden)

    Yukako Murakami

    2011-01-01

    Full Text Available We report a case of 7-year-old monozygotic twin patients with atopic dermatitis. The HLA haplotypes were HLA A2, A11, B27, B61, DR1, and DR4. Both serum IgE levels and cedar pollen radioallergosorbent test (RAST scores were high in the twins (elder/younger sister: IgE: 5170/3980 IU/ml and Japansese cedar pollen: >100/64.0 in contrast to low mite and food RAST scores (Dermatophagoides Pterygonium; 0.59/0.4 and egg white 9.24/4.6. The patients showed positive immediate (20 min in both sisters and delayed (24 hours in elder sister, 24, 48, 72 hours in younger sister reactions to a scratch test with Japanese cedar pollen. Skin lesions on the face were aggravated and extended to the trunk and extremities during the Japanese cedar pollen season and gradually subsided in summer. Oral provocation with egg white or cow milk showed no exacerbations, and topical corticosteroid did not improve the eczema. In contrast, successful protection from severe scratching behaviors was achieved by use of topical anti-allergic eye drops and wearing nightgowns made by the mother.

  2. Dietary fructose aggravates the pathobiology of traumatic brain injury by influencing energy homeostasis and plasticity.

    Science.gov (United States)

    Agrawal, Rahul; Noble, Emily; Vergnes, Laurent; Ying, Zhe; Reue, Karen; Gomez-Pinilla, Fernando

    2016-05-01

    Fructose consumption has been on the rise for the last two decades and is starting to be recognized as being responsible for metabolic diseases. Metabolic disorders pose a particular threat for brain conditions characterized by energy dysfunction, such as traumatic brain injury. Traumatic brain injury patients experience sudden abnormalities in the control of brain metabolism and cognitive function, which may worsen the prospect of brain plasticity and function. The mechanisms involved are poorly understood. Here we report that fructose consumption disrupts hippocampal energy homeostasis as evidenced by a decline in functional mitochondria bioenergetics (oxygen consumption rate and cytochrome C oxidase activity) and an aggravation of the effects of traumatic brain injury on molecular systems engaged in cell energy homeostasis (sirtuin 1, peroxisome proliferator-activated receptor gamma coactivator-1alpha) and synaptic plasticity (brain-derived neurotrophic factor, tropomyosin receptor kinase B, cyclic adenosine monophosphate response element binding, synaptophysin signaling). Fructose also worsened the effects of traumatic brain injury on spatial memory, which disruption was associated with a decrease in hippocampal insulin receptor signaling. Additionally, fructose consumption and traumatic brain injury promoted plasma membrane lipid peroxidation, measured by elevated protein and phenotypic expression of 4-hydroxynonenal. These data imply that high fructose consumption exacerbates the pathology of brain trauma by further disrupting energy metabolism and brain plasticity, highlighting the impact of diet on the resilience to neurological disorders.

  3. 147 Mitigating and Aggravating Circumstances. Their Impact on Judicial Individualization of Punishment

    Directory of Open Access Journals (Sweden)

    Cosmin Peonaşu

    2015-08-01

    Full Text Available For an act to fall under criminal law it is sufficient for it to meet the minimum conditions to achieve constitutive content of the offense. However, committing a criminal act takes place, in most cases, in a complex set of variables specific to each case, variables that, without characterizing the act as an offense or the perpetrator's person as subject of that offence, helps determining, on one hand, the social danger of the committed crime and, on the other hand, knowing the offender as an individual and its social dangerousness. Mitigating and aggravating circumstances are such variables and they have a specific impact on criminal responsibility of the perpetrator. These circumstances have a major influence on judicial individualization of punishment because their effect is preset by the Law and acts separately on the length or amount of punishment. This study aims both students and practitioners or academics and highlights on one hand, the legislative solutions of the new Criminal Code and on the other hand, the differences between the old and the new Criminal Code.

  4. Homocysteine Aggravates Cortical Neural Cell Injury through Neuronal Autophagy Overactivation following Rat Cerebral Ischemia-Reperfusion

    Directory of Open Access Journals (Sweden)

    Yaqian Zhao

    2016-07-01

    Full Text Available Elevated homocysteine (Hcy levels have been reported to be involved in neurotoxicity after ischemic stroke. However, the underlying mechanisms remain incompletely understood to date. In the current study, we hypothesized that neuronal autophagy activation may be involved in the toxic effect of Hcy on cortical neurons following cerebral ischemia. Brain cell injury was determined by hematoxylin-eosin (HE staining and TdT-mediated dUTP Nick-End Labeling (TUNEL staining. The level and localization of autophagy were detected by transmission electron microscopy, western blot and immunofluorescence double labeling. The oxidative DNA damage was revealed by immunofluorescence of 8-Hydroxy-2′-deoxyguanosine (8-OHdG. Hcy treatment aggravated neuronal cell death, significantly increased the formation of autophagosomes and the expression of LC3B and Beclin-1 in the brain cortex after middle cerebral artery occlusion-reperfusion (MCAO. Immunofluorescence analysis of LC3B and Beclin-1 distribution indicated that their expression occurred mainly in neurons (NeuN-positive and hardly in astrocytes (GFAP-positive. 8-OHdG expression was also increased in the ischemic cortex of Hcy-treated animals. Conversely, LC3B and Beclin-1 overexpression and autophagosome accumulation caused by Hcy were partially blocked by the autophagy inhibitor 3-methyladenine (3-MA. Hcy administration enhanced neuronal autophagy, which contributes to cell death following cerebral ischemia. The oxidative damage-mediated autophagy may be a molecular mechanism underlying neuronal cell toxicity of elevated Hcy level.

  5. Cardiac Fibroblasts Aggravate Viral Myocarditis: Cell Specific Coxsackievirus B3 Replication

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    Diana Lindner

    2014-01-01

    Full Text Available Myocarditis is an inflammatory disease caused by viral infection. Different subpopulations of leukocytes enter the cardiac tissue and lead to severe cardiac inflammation associated with myocyte loss and remodeling. Here, we study possible cell sources for viral replication using three compartments of the heart: fibroblasts, cardiomyocytes, and macrophages. We infected C57BL/6j mice with Coxsackievirus B3 (CVB3 and detected increased gene expression of anti-inflammatory and antiviral cytokines in the heart. Subsequently, we infected cardiac fibroblasts, cardiomyocytes, and macrophages with CVB3. Due to viral infection, the expression of TNF-α, IL-6, MCP-1, and IFN-β was significantly increased in cardiac fibroblasts compared to cardiomyocytes or macrophages. We found that in addition to cardiomyocytes cardiac fibroblasts were infected by CVB3 and displayed a higher virus replication (132-fold increase compared to cardiomyocytes (14-fold increase between 6 and 24 hours after infection. At higher virus concentrations, macrophages are able to reduce the viral copy number. At low virus concentration a persistent virus infection was determined. Therefore, we suggest that cardiac fibroblasts play an important role in the pathology of CVB3-induced myocarditis and are another important contributor of virus replication aggravating myocarditis.

  6. Cardiomyocyte Overexpression of FABP4 Aggravates Pressure Overload-Induced Heart Hypertrophy.

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    Ji Zhang

    Full Text Available Fatty acid binding protein 4 (FABP4 is a member of the intracellular lipid-binding protein family, responsible for the transportation of fatty acids. It is considered to express mainly in adipose tissues, and be strongly associated with inflammation, obesity, diabetes and cardiovasculardiseases. Here we report that FABP4 is also expressed in cardiomyocytes and plays an important role in regulating heart function under pressure overload. We generated heart-specific transgenic FABP4 (FABP4-TG mice using α myosin-heavy chain (α-MHC promoter and human FABP4 sequence, resulting in over-expression of FABP4 in cardiomyocytes. The FABP4-TG mice displayed normal cardiac morphology and contractile function. When they were subjected to the transverse aorta constriction (TAC procedure, the FABP4-TG mice developed more cardiac hypertrophy correlated with significantly increased ERK phosphorylation, compared with wild type controls. FABP4 over-expression in cardiomyocytes activated phosphor-ERK signal and up-regulate the expression of cardiac hypertrophic marker genes. Conversely, FABP4 induced phosphor-ERK signal and hypertrophic gene expressions can be markedly inhibited by an ERK inhibitor PD098059 as well as the FABP4 inhibitor BMS309403. These results suggest that FABP4 over-expression in cardiomyocytes can aggravate the development of cardiac hypertrophy through the activation of ERK signal pathway.

  7. Norepinephrine as a Potential Aggravator of Symptomatic Cerebral Vasospasm: Two Cases and Argument for Milrinone Therapy

    Directory of Open Access Journals (Sweden)

    F. A. Zeiler

    2014-01-01

    Full Text Available Background. During hypertensive therapy for post-subarachnoid hemorrhage (SAH symptomatic vasospasm, norepinephrine is commonly used to reach target blood pressures. Concerns over aggravation of vasospasm with norepinephrine exist. Objective. To describe norepinephrine temporally related deterioration in neurological examination of two post-SAH patients in vasospasm. Methods. We retrospectively reviewed two charts of patients with delayed cerebral ischemia (DCI post-SAH who deteriorated with norepinephrine infusions. Results. We identified two patients with DCI post-SAH who deteriorated during hypertensive therapy with norepinephrine. The first, a 43-year-old male presented to hospital with DCI, failed MABP directed therapy with rapid deterioration in exam with high dose norepinephrine and MABP of 140–150 mm Hg. His exam improved on continuous milrinone and discontinuation of norepinephrine. The second, a 39-year-old female who developed DCI on postbleed day 8 responded to milrinone therapy upfront. During further deterioration and after angioplasty, norepinephrine was utilized to drive MABP to 130–140 mm Hg. Progressive deterioration in examination occurred after angioplasty as norepinephrine doses escalated. After discontinuation of norepinephrine and continuation of milrinone, function dramatically returned but not to baseline. Conclusions. The potential exists for worsening of DCI post-SAH with hypertensive therapy directed by norepinephrine. A potential role exists for vasodilation and inotropic directed therapy with milrinone in the setting of DCI post-SAH.

  8. Carbon monoxide pollution aggravates ischemic heart failure through oxidative stress pathway.

    Science.gov (United States)

    Reboul, Cyril; Boissière, Julien; André, Lucas; Meyer, Gregory; Bideaux, Patrice; Fouret, Gilles; Feillet-Coudray, Christine; Obert, Philippe; Lacampagne, Alain; Thireau, Jérôme; Cazorla, Olivier; Richard, Sylvain

    2017-01-03

    Risk of hospital readmission and cardiac mortality increases with atmospheric pollution for patients with heart failure. The underlying mechanisms are unclear. Carbon monoxide (CO) a ubiquitous environmental pollutant could be involved. We explored the effect of daily exposure of CO relevant to urban pollution on post-myocardial infarcted animals. Rats with ischemic heart failure were exposed 4 weeks to daily peaks of CO mimicking urban exposure or to standard filtered air. CO exposure worsened cardiac contractile dysfunction evaluated by echocardiography and at the cardiomyocyte level. In line with clinical reports, the animals exposed to CO also exhibited a severe arrhythmogenic phenotype with numerous sustained ventricular tachycardias as monitored by surface telemetric electrocardiograms. CO did not affect cardiac β-adrenergic responsiveness. Instead, mitochondrial dysfunction was exacerbated leading to additional oxidative stress and Ca(2+) cycling alterations. This was reversed following acute antioxidant treatment of cardiomyocytes with N-acetylcysteine confirming involvement of CO-induced oxidative stress. Exposure to daily peaks of CO pollution aggravated cardiac dysfunction in rats with ischemic heart failure by specifically targeting mitochondria and generating ROS-dependent alterations. This pathway may contribute to the high sensibility and vulnerability of individuals with cardiac disease to environmental outdoor air quality.

  9. Fasciola hepatica: Histological changes in the somatic and reproductive tissues of liver fluke following closantel treatment of experimentally-infected sheep.

    Science.gov (United States)

    Scarcella, S; Hanna, R E B; Brennan, G P; Solana, H; Fairweather, I

    2016-01-15

    Lambs infected with the Cullompton isolate of Fasciola hepatica were treated orally or subcutaneously with 10mg/kg of closantel at 16 weeks post-infection. Adult flukes were recovered from the liver of individual animals at 12h, 24h, or 36h post-treatment. The flukes were processed for histological analysis. In general, degenerative changes in the reproductive and somatic tissues were progressive, and were most marked in flukes exposed to closantel in vivo for 36h. However, flukes from a 12h subcutaneously-treated lamb showed marked deterioration of the testis, possibly because a portion of the dose has been delivered intravenously. Fewer intact eggs were seen in the uterus of flukes exposed to closantel for longer times (whether administered subcutaneously or orally to the host). The most conspicuous closantel-induced effect in flukes from treated hosts was progressive damage to the tegumental syncytium. While the flukes from 24h-treated hosts showed relatively minor damage to limited areas of the syncytium, towards the posterior end, the flukes from 36h-treated hosts (and flukes from the lamb that putatively received intravenous dosage) had lost large areas of the surface syncytium from the posterior end and dorsal surface, although the syncytium over the anterior end and the anterior ventral surface was largely spared. In areas where the syncytium had sloughed, the underlying structures such as the vitelline follicles, gut profiles and testis profiles, showed marked degeneration and breakdown. Other changes included cell depletion and early stage apoptosis in the testis, ovary and vitelline follicles. This study establishes a model for histological changes in closantel-sensitive F. hepatica exposed to closantel in vivo. Histopathological studies could be complementary to the efficacy controlled test for for closantel resistance in fluke populations.

  10. Establishment and evaluation of an experimental chicken model of fatty liver hemorrhagic syndrome%实验性鸡脂肪肝出血综合征模型的建立与评价

    Institute of Scientific and Technical Information of China (English)

    姜锦鹏; 宁康健; 吕锦芳; 李升和; 车传燕; 应如海; 许雪萍; 冯保明

    2012-01-01

    replications of 20 birds in each group): Control (C), high-fat diet (HF), estrogen injection (E), and high fat diet plus estrogen injection (HF + E) groups. The experimental period lasted from 15 to 42 days. Two 14-day periods were used to assess different factors. The clinical symptoms of the chickens were monitored each day over the experimental period. Abdominal fat weight, pathological changes, serum and liver parameters were measured at the end of each 14-d periods. Results FLHS occurred in the group HF + E at 14th day whereas FLHS didn' t occur in the control group till 28* day. The group HF+E showed obvious clinical symptoms such as mouth breathing, excessive sleepiness and abdominal sag in some birds 10 days later. Excessive fat deposition in the abdominal cavity and swollen, brown-yellow, friable, blunt and hemorrhagic liver were observed on day 14 and 28. Slight hepatocyte steatosis and small lipid vacuoles in cytoplasm were observed on day 14. A large number of hepatocytes displayed distinct pathological changes such as histological disarrangement, swelling and large lipid vacuoles in cytoplasm on day 28. The FLHS incidence was higher at 28th day compared with that on the 14th day. The serum triglycer-ide and total cholesterol, the relative weight of liver and abdominal fat, liver fat rate and liver hemorrhage score (LHS) were increased significantly compared with those in the control group on day 14 and 28 ( P < 0. 05, P < 0. 01). The clinical symptoms, anatomic characteristics, pathological changes, blood biochemical indices and other findings in the group E and HF were similar to those in the group HF + E, but to a less severe degree and the time of occurrence was later than that in the group HF + E. Conclusion The results of this study suggest that high fat diet combined with estrogen administration can successfully establish model of fatty liver hemorrhagic syndrome in immature chickens within 28 days.

  11. Cavernous Transformation of the Portal Vein Might Increase the Risk of Liver Abscess

    Directory of Open Access Journals (Sweden)

    Xin-Bo Ai

    2010-09-01

    Full Text Available Cavernous transformation of the portal vein (CTPV is not quite common in adults, and cases with CTPV and acute liver abscess are lacking. We report a patient with CTPV inducing extrahepatic and intrahepatic obstruction, finally leading to acute liver abscess due to bile duct infection. We aim to find out the possible relationship between CTPV and acute liver abscess. A 45-year-old female patient was admitted to our hospital for recurrent upper abdominal pain and distension for one year, aggravated with fever for three years. A diagnosis of CTPV and liver abscess was made by 16-slice computed tomography. Effective antibiotics and drainage were used for this patients, and she was eventually cured. When treating patients with CTPV, extrahepatic and intrahepatic obstruction, one should be aware of the presence of acute liver abscess, and empirical antibiotics might be valuable.

  12. Modelo experimental de indução de lesão oxidativa hepática em ratos por halotano Experimental model of liver oxidative damage induction in rats by halothane

    Directory of Open Access Journals (Sweden)

    Luis Josino Brasil

    2007-03-01

    Full Text Available RACIONAL: O anestésico halotano pode ser metabolizado redutivamente a intermediários reativos que podem iniciar a lipoperoxidação acompanhada de injúria hepática. O tratamento prévio com hipóxia e fenobarbital em ratos aumenta o metabolismo do halotano e o estresse oxidativo e causa mudanças nas enzimas antioxidantes no fígado com dano hepático. MÉTODOS: Investigou-se o efeito do halotano na lipoperoxidação e histologia hepáticas após o aumento do metabolismo redutor do halotano induzido pela hipóxia e fenobarbital. Vinte e cinco ratos machos Wistar foram divididos em cinco grupos: Co (controle, HO14 (Halotano/Hipóxia, F (Fenobarbital, O14 (Hipóxia e H (Halotano. Após 24 horas os ratos foram sacrificados, seus fígados foram retirados para determinar quimiluminescência, substâncias que reagem ao ácido tiobarbitúrico, enzimas antioxidantes, superóxido dismutase, catalase e amostras de sangue foram tomadas para determinar AST e a ALT. A avaliação histopatológica foi realizada pela técnica de hematoxilina-eosina. Os dados da avaliação histológica foram apresentados através de mediana e amplitude entre quartis. RESULTADOS E CONCLUSÕES: A exposição ao halotano/hipóxia causou lipoperoxidação hepática e mudanças significativas na atividade das enzimas antioxidantes. Além disso, provocou lesão histopatológica do fígado e aumento significativo dos níveis plasmáticos de AST e ALT.BACKGROUND: The anesthetic halothane can be reductively metabolized to reactives intermediates that may initiate lipid peroxidation accompanied by hepatic injury. Hypoxia and phenobarbital pretreatment in rats increases metabolism of halothane, the oxidative stress, cause liver antioxidant enzymes changes and tissue damage. AIMS: We investigated the effect of halothane on hepatic lipid peroxidation and on hepatic histology after increases reductive metabolism of halothane caused by hypoxia and phenobarbital pretreatment. METHODS

  13. Experimental study of Gynostemma pentaphyllum on inhibiting lipid deposition in rabbit liver with nonalcohol fatty liver disease%绞股蓝抑制非酒精性脂肪性肝病兔肝脏脂质沉积的实验研究

    Institute of Scientific and Technical Information of China (English)

    刘其政; 孙希杰; 谭华炳; 吴凡; 胡波

    2011-01-01

    Objective; To study the effect of gynostemma pentaphyllum inhibiting lipid deposition in rabbit liver with nonal-cohol fatty liver disease, and discuss the mechanism. Methods; Forty Japanese adult male white rabbits with NAFLD were randomly divided into intervention group of gynostemma pentaphyllum (Group A) , intervention group of simvastatin (Group B), pattern group (Group C) , the control group (Group E) , respectively every group was given high fat and gynostemma pentaphyllum diet 5g/kg, high fat and simvastatin diet 5g/kg, high fat diet, standard diet, the experimental cycle was 9 weeks. And synchronously tested triglyceride (TG) , cholesterol (TCh) before and after experiment. Made liver tissue homogenate, detected the weight of TG in liver tissue homogenate. Pathological changes of liver tissue were observed in order to realize the degree of NNAFLD . Results; ①TCh and TG level: Before and after the experiment group A, group B and group C there was a significant difference (P < 0. 01) . After the feeding, TG and TCh of group A and group B were lower than group C, there was a significant difference ( P < 0.01) ; the TG of group A were lower than group B, there was a significant difference ( P < 0.01);the TCh of group B were lower than group A, there was a significant difference (P < 0.01) . ②The TG level of liver tissue; The TG of group A and group B were lower than group C, there was a significant difference ( P < 0.01) . The TG of group A were lower than group B, there was a significant difference (P < 0. 01) . ③Liver pathology: The liver of group D was ruddy soft, the livers of group A, B, C were diffuse enlargement, edge blunt and thick, tawny. The colour and lustre of group A was ruddyer than group B and group C; the degree of enlargement was lighter. With the Trypan-blue, structure and cells form of group D was normal, 2/3 above cell of group A changed with adipose kind, one hundred percent nearly cell of group B and group C changed withadipose

  14. Tumor hepático experimental (VX-2 em coelho: implantação do modelo no Brasil Experimental liver tumor (VX-2 in rabbits: implantation of the model in Brazil

    Directory of Open Access Journals (Sweden)

    Rogério Saad Hossne

    2002-08-01

    Full Text Available Os estudos para a investigação de novas modalidades terapêuticas em biologia tumoral, deveriam passar por estudos experimentais prévios. Neste sentido dispõem-se hoje de uma grande variedade de modelos tumorais experimentais; em determinadas investigações faz-se necessária a adequação do modelo tumoral às necessidades biológicas, patológicas e experimentais dos estudos. Desta forma, em nosso serviço, buscávamos um modelo tumoral hepático para estudos experimentais que se adequasse às seguintes características: fácil manipulação, crescimento controlável, evolução e agressividade semelhantes aos seres humanos. Os dados da literatura nos levaram a busca do tumor hepático VX-2, em coelhos. Neste artigo discutimos as vantagens da utilização deste modelo experimental e a sua introdução em nosso país.Studies for investigation of new therapeutic modalities in tumoral biology should be based on previous experimental studies. Then, there are a great variety of tumoral experimental models today. Some investigations have been done necessary an adaptation of the tumoral model to the needing of the studies biological and pathological. So, in our laboratory, we looked for a tumoral hepatic model for experimental studies with the following characteristics: easy manipulation, control of growing, evolution and aggressiveness like to humans. Data of the literature took us the search of the hepatic tumor VX-2, in rabbits. In this article we discussed the advantages of use this experimental model and its introduction in our country. Experimental hepatic tumor (VX-2 in rabbit. Implantation of the model in Brazil.

  15. Cobalamin inactivation by nitrous oxide produces severe neurological impairment in fruit bats: protection by methionine and aggravation by folates

    Energy Technology Data Exchange (ETDEWEB)

    van der Westhuyzen, J.; Fernandes-Costa, F.; Metz, J.

    1982-11-01

    Nitrous oxide, which inactivates cobalamin when administered to fruit bats, results in severe neurological impairment leading to ataxia, paralysis and death. This occurs after about 6 weeks in animals depleted of cobalamin by dietary restriction, and after about 10 weeks in cobalamin replete bats. Supplementation of the diet with pteroylglutamic acid caused acceleration of the neurological impairment--the first unequivocal demonstration of aggravation of the neurological lesion in cobalamin deficiency by pteroylglutamic acid. The administration of formyltetrahydropteroylglutamic acid produced similar aggravation of the neurological lesion. Supplementation of the diet with methionine protected the bats from neurological impairment, but failed to prevent death. Methionine supplementation protected against the exacerbating effect of folate, preventing the development of neurological changes. These findings lend support to the hypothesis that the neurological lesion in cobalamin deficiency may be related to a deficiency in the methyl donor S-adenosylmethionine which follows diminished synthesis of methionine.

  16. Charges for criminal exposure to HIV and aggravated prostitution filed in the Nashville, Tennessee Prosecutorial Region 2000-2010.

    Science.gov (United States)

    Galletly, Carol L; Lazzarini, Zita

    2013-10-01

    This paper examines comprehensive data on arrests for HIV-specific crimes within a single jurisdiction, the Nashville Tennessee prosecutorial region, over 11 years. There were 25 arrests for HIV exposure and 27 for aggravated prostitution. Eleven of the arrests for HIV exposure involved nonsexual behaviors; none alleged transmission. Sixteen of the arrests for HIV exposure involved sexual behavior; three alleged transmission. Aggravated prostitution cases (i.e. prostitution while knowing one has HIV) often involved solicitation of oral sex; none alleged transmission. Maximum sentences for HIV-specific crimes ranged from 5 to 8 years. We conclude that enforcement of US HIV-specific laws is underestimated. Fifty-two arrests over 11 years were recorded in one jurisdiction. Over half of the arrests involved behaviors posing minimal or no HIV transmission risk. Despite concerns about malicious, intentional HIV transmission, no cases alleged malice or intention.

  17. Aggravated bone density decline following symptomatic osteonecrosis in children with acute lymphoblastic leukemia.

    Science.gov (United States)

    den Hoed, Marissa A H; Pluijm, Saskia M F; te Winkel, Mariël L; de Groot-Kruseman, Hester A; Fiocco, Martha; Hoogerbrugge, Peter; Leeuw, Jan A; Bruin, Marrie C A; van der Sluis, Inge M; Bresters, Dorien; Lequin, Maarten H; Roos, Jan C; Veerman, Anjo J P; Pieters, Rob; van den Heuvel-Eibrink, Marry M

    2015-12-01

    Osteonecrosis and decline of bone density are serious side effects during and after treatment of childhood acute lymphoblastic leukemia. It is unknown whether osteonecrosis and low bone density occur together in the same patients, or whether these two osteogenic side-effects can mutually influence each other's development. Bone density and the incidence of symptomatic osteonecrosis were prospectively assessed in a national cohort of 466 patients with acute lymphoblastic leukemia (4-18 years of age) who were treated according to the dexamethasone-based Dutch Child Oncology Group-ALL9 protocol. Bone mineral density of the lumbar spine (BMDLS) (n=466) and of the total body (BMDTB) (n=106) was measured by dual X-ray absorptiometry. Bone density was expressed as age- and gender-matched standard deviation scores. Thirty patients (6.4%) suffered from symptomatic osteonecrosis. At baseline, BMDLS and BMDTB did not differ between patients who did or did not develop osteonecrosis. At cessation of treatment, patients with osteonecrosis had lower mean BMDLS and BMDTB than patients without osteonecrosis (respectively, with osteonecrosis: -2.16 versus without osteonecrosis: -1.21, Posteonecrosis: -1.73 versus without osteonecrosis: -0.57, Posteonecrosis had steeper BMDLS and BMDTB declines during follow-up than patients without osteonecrosis (interaction group time, Posteonecrosis. Bone density declines from the time that osteonecrosis is diagnosed; this suggests that the already existing decrease in bone density during acute lymphoblastic leukemia therapy is further aggravated by factors such as restriction of weight-bearing activities and destruction of bone architecture due to osteonecrosis. Osteonecrosis can, therefore, be considered a risk factor for low bone density in children with acute lymphoblastic leukemia.

  18. Vitamin D deficiency aggravates chronic kidney disease progression after ischemic acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Janaína Garcia Gonçalves

    pathways and involvement of TGF-β1 growth factor, VDD could be considered as an aggravating factor for tubulointerstitial damage and fibrosis progression following acute kidney injury induced by ischemia/reperfusion.

  19. Chemerin aggravates DSS-induced colitis by suppressing M2 macrophage polarization.

    Science.gov (United States)

    Lin, Yuli; Yang, Xuguang; Yue, Wenjie; Xu, Xiaofei; Li, Bingji; Zou, Linlin; He, Rui

    2014-07-01

    Chemerin is present in various inflammatory sites and is closely involved in tissue inflammation. Recent studies have demonstrated that chemerin treatment can cause either anti-inflammatory or pro-inflammatory effects according to the disease model being investigated. Elevated circulating chemerin was recently found in patients with inflammatory bowel disease (IBD); however, the role of chemerin in intestinal inflammation remains unknown. In this study, we demonstrated that the administration of exogenous chemerin (aa17-156) aggravated the severity of dextran sulfate sodium (DSS)-induced colitis, which was characterized by higher clinical scores, extensive mucosal damage and significantly increased local and systemic production of pro-inflammatory cytokines, including IL-6, TNF-α and interferon (IFN-γ). Interestingly, chemerin did not appear to influence the magnitudes of inflammatory infiltrates in the colons, but did result in significantly decreased colonic expression of M2 macrophage-associated genes, including Arginase 1 (Arg-1), Ym1, FIZZ1 and IL-10, following DSS exposure, suggesting an impaired M2 macrophage skewing in vivo. Furthermore, an in vitro experiment showed that the addition of chemerin directly suppressed M2 macrophage-associated gene expression and STAT6 phosphorylation in IL-4-stimulated macrophages. Significantly elevated chemerin levels were found in colons from DSS-exposed mice and from ulcerative colitis (UC) patients and appeared to positively correlate with disease severity. Moreover, the in vivo administration of neutralizing anti-chemerin antibody significantly improved intestinal inflammation following DSS exposure. Taken together, our findings reveal a pro-inflammatory role for chemerin in DSS-induced colitis and the ability of chemerin to suppress the anti-inflammatory M2 macrophage response. Our study also suggests that upregulated chemerin in inflamed colons may contribute to the pathogenesis of IBD.

  20. Disinhibition of Cathepsin C Caused by Cystatin F Deficiency Aggravates the Demyelination in a Cuprizone Model

    Science.gov (United States)

    Liang, Junjie; Li, Ning; Zhang, Yanli; Hou, Changyi; Yang, Xiaohan; Shimizu, Takahiro; Wang, Xiaoyu; Ikenaka, Kazuhiro; Fan, Kai; Ma, Jianmei

    2016-01-01

    Although the precise mechanism underlying initial lesion development in multiple sclerosis (MS) remains unclear, CNS inflammation has long been associated with demyelination, and axonal degeneration. The activation of microglia/macrophages, which serve as innate immune cells in the CNS, is the first reaction to even minor pathologic changes in the CNS and is considered an initial pathogenic event in MS. Microglial activation accompanies a variety of gene expressions, including cystatin F (Cys F), which belongs to the cystatin superfamily and is one of the cathepsin inhibitors. In our previous study we showed that Cys F has a unique expression pattern in microglia/macrophages in the demyelination process. Specifically, the timing of Cys F induction correlated with ongoing demyelination, and the sites of Cys F expression overlapped with areas of remyelination. Cys F induction ceased in chronic demyelination when remyelination capacity was lost, suggesting that Cys F expressed by microglia/macrophages may play an important role in demyelination and/or remyelination. The functional role of Cys F in demyelinating disease of the CNS, however, is unclear. Cys F gene knockout mice were used in the current study to clarify the functional role of Cys F in the demyelination process in a cuprizone-induced demyelination animal model. We demonstrated that absence of the Cys F gene and the resulting disinhibition of cathepsin C (Cat C) aggravates the demyelination, and this finding may be related to the increased expression of the glia-derived chemokine, CXCL2, which may attract inflammatory cells to sites of myelin sheath damage. This effect was reversed by knock down of the Cat C gene. The findings gain further insight to function of Cat C in pathophysiology of MS, which may have implications for therapeutics for the prevention of neuroinflammation-involved neurological disorders in the future. PMID:28066178

  1. High Potassium Aggravates the Oxidative Stress Inducedy by Magnesium Deficiency in Rice Leaves

    Institute of Scientific and Technical Information of China (English)

    DING Yu-Chuan; CHANG Chun-Rong; LUO Wen; WU Yan-Shou; REN Xiao-Li; WANG Ping; XU Guo-Hua

    2008-01-01

    Magnesium (Mg) deficiency in plant affects photosynthesis and many other metabolic processes.Rice (Oryza sativa L.cv.'Wuyunjing 7') plants were grown in hydroponics culture at three Mg and two potassium (K) levels under greenhouse conditions to examine the induction of oxidative stress and consequent antioxidant responses in rice leaves due to Mg deficiency.At low Mg (0.2 mmol L-1 Mg supply for two weeks after transplanting) and high K (6 mmol L-1) for 21days,the rice plants showed severe Mg deficiency and a significant decreases in the dry matter production. The Mg deficiency in leaves decreased chlorophyll concentrations,photosynthetic activity,and soluble protein,but significantly increased the concentrations of soluble sugars and malondialdehyde (MDA) and the activities of superoxide dismutase (SOD,EC 1.15.1.1),catalase (CAT,EC 1.11.1.6) and peroxidase (POD,EC 1.11.1.7).In addition,Mg concentrations in the leaves and in the shoot biomass were negatively related to the activities of the three antioxidative enzymes and the concentration of MDA in leaves.There were very significant interactive effects between Mg and K supplied in the culture solution on shoot biomass yield,chlorophyll content,photosynthesis rate,the activities of SOD,CAT and POD,and MDA content in the leaves of rice.It is suggested that the high K level in the nutrient solution aggravated the effect of low Mg supply-induced Mg deficiency and created the oxidative damage in rice plants.

  2. Cigarette smoke exposure aggravates air space enlargement and alveolar cell apoptosis in Smad3 knockout mice.

    Science.gov (United States)

    Farkas, Laszlo; Farkas, Daniela; Warburton, David; Gauldie, Jack; Shi, Wei; Stampfli, Martin R; Voelkel, Norbert F; Kolb, Martin

    2011-10-01

    The concept of genetic susceptibility factors predisposing cigarette smokers to develop emphysema stems from the clinical observation that only a fraction of smokers develop clinically significant chronic obstructive pulmonary disease. We investigated whether Smad3 knockout mice, which develop spontaneous air space enlargement after birth because of a defect in transforming growth factor-β (TGF-β) signaling, develop enhanced alveolar cell apoptosis and air space enlargement following cigarette smoke exposure. We investigated Smad3(-/-) and Smad3(+/+) mice at different adult ages and determined air space enlargement, alveolar cell proliferation, and apoptosis. Furthermore, laser-capture microdissection and real-time PCR were used to measure compartment-specific gene expression. We then compared the effects of cigarette smoke exposure on Smad3(-/-) and littermate controls. Smad3 knockout resulted in the development of air space enlargement in the adult mouse and was associated with decreased alveolar VEGF levels and activity and increased alveolar cell apoptosis. Cigarette smoke exposure aggravated air space enlargement and alveolar cell apoptosis. We also found increased Smad2 protein expression and phosphorylation, which was enhanced following cigarette smoke exposure, in Smad3-knockout animals. Double immunofluorescence analysis revealed that endothelial apoptosis started before epithelial apoptosis. Our data indicate that balanced TGF-β signaling is not only important for regulation of extracellular matrix turnover, but also for alveolar cell homeostasis. Impaired signaling via the Smad3 pathway results in alveolar cell apoptosis and alveolar destruction, likely via increased Smad2 and reduced VEGF expression and might represent a predisposition for accelerated development of emphysema due to cigarette smoke exposure.

  3. The thyroid function of Graves' disease patients is aggravated by depressive personality during antithyroid drug treatment

    Directory of Open Access Journals (Sweden)

    Miyauchi Akira

    2011-08-01

    thyrotoxicosis and that it aggravates hyperthyroidism. Psychosomatic therapeutic approaches including antipsychiatric drugs and/or psychotherapy appears to be useful for improving the prognosis of hyperthyroidism.

  4. Respiratory Syncytial Virus Aggravates Renal Injury through Cytokines and Direct Renal Injury

    Directory of Open Access Journals (Sweden)

    Songhui Zhai

    2016-09-01

    Full Text Available The purpose of this study was to investigate the relationship between renal injury and reinfection that is caused by respiratory syncytial virus (RSV and to analyze the mechanism of renal injury. Rats were repeatedly infected with RSV on days 4, 8, 14, and 28, then sacrificed and examined on day 56 after the primary infection. Renal injury was examined by transmission electron microscopy and histopathology. The F protein of RSV was detected in the renal tissue by indirect immunofluorescence. Proteinuria and urinary glycosaminoglycans (GAGs, serum levels of albumin, urea nitrogen, and creatinine, secretion of cytokines, T lymphocyte population and subsets, and dendritic cell (DC activation state were examined. The results showed that renal injury was more serious in the reinfection group than in the primary infection group. At a higher infection dose, 6×106 PFU, the renal injury was more severe, accompanied by higher levels of proteinuria and urinary GAGs excretion, and lower levels of serum albumin. Podocyte foot effacement was more extensive, and hyperplasia of mesangial cells and proliferation of mesangial matrix were observed. The maturation state of DCs was specific, compared with the primary infection. There was also a decrease in the ratio of CD4+ to CD8+T lymphocytes, due to an increase in the percentage of CD8+T lymphocytes and a decrease in the percentage of CD4+T lymphocytes, and a dramatic increase in the levels of IL-6 and IL-17. In terms of the different reinfection times, the day 14 reinfection group yielded the most serious renal injury and the most significant change in immune function. RSV F protein was still expressed in the glomeruli 56 days after RSV infection. Altogether, these results reveal that RSV infection could aggravate renal injury, which might be due to direct renal injury caused by RSV and the inflammatory lesions caused by the anti-virus response induced by RSV.

  5. Right Cervical Vagotomy Aggravates Viral Myocarditis in Mice Via the Cholinergic Anti-inflammatory Pathway

    Science.gov (United States)

    Li-Sha, Ge; Xing-Xing, Chen; Lian-Pin, Wu; De-Pu, Zhou; Xiao-Wei, Li; Jia-Feng, Lin; Yue-Chun, Li

    2017-01-01

    The autonomic nervous system dysfunction with increased sympathetic activity and withdrawal of vagal activity may play an important role in the pathogenesis of viral myocarditis. The vagus nerve can modulate the immune response and control inflammation through a ‘cholinergic anti-inflammatory pathway’ dependent on the α7-nicotinic acetylcholine receptor (α7nAChR). Although the role of β-adrenergic stimulation on viral myocarditis has been investigated in our pervious studies, the direct effect of vagal tone in this setting has not been yet studied. Therefore, in the present study, we investigated the effects of cervical vagotomy in a murine model of viral myocarditis. In a coxsackievirus B3 murine myocarditis model (Balb/c), effects of right cervical vagotomy and nAChR agonist nicotine on echocardiography, myocardial histopathology, viral RNA, and proinflammatory cytokine levels were studied. We found that right cervical vagotomy inhibited the cholinergic anti-inflammatory pathway, aggravated myocardial lesions, up-regulated the expression of TNF-α, IL-1β, and IL-6, and worsened the impaired left ventricular function in murine viral myocarditis, and these changes were reversed by co-treatment with nicotine by activating the cholinergic anti-inflammatory pathway. These results indicate that vagal nerve plays an important role in mediating the anti-inflammatory effect in viral myocarditis, and that cholinergic stimulation with nicotine also plays its peripheral anti-inflammatory role relying on α7nAChR, without requirement for the integrity of vagal nerve in the model. The findings suggest that vagus nerve stimulation mediated inhibition of the inflammatory processes likely provide important benefits in myocarditis treatment. PMID:28197102

  6. Aggravation of Allergic Airway Inflammation by Cigarette Smoke in Mice Is CD44-Dependent.

    Directory of Open Access Journals (Sweden)

    Smitha Kumar

    Full Text Available Although epidemiological studies reveal that cigarette smoke (CS facilitates the development and exacerbation of allergic asthma, these studies offer limited information on the mechanisms involved. The transmembrane glycoprotein CD44 is involved in cell adhesion and acts as a receptor for hyaluronic acid and osteopontin. We aimed to investigate the role of CD44 in a murine model of CS-facilitated allergic airway inflammation.Wild type (WT and CD44 knock-out (KO mice were exposed simultaneously to house dust mite (HDM extract and CS. Inflammatory cells, hyaluronic acid (HA and osteopontin (OPN levels were measured in bronchoalveolar lavage fluid (BALF. Proinflammatory mediators, goblet cell metaplasia and peribronchial eosinophilia were assessed in lung tissue. T-helper (Th 1, Th2 and Th17 cytokine production was evaluated in mediastinal lymph node cultures.In WT mice, combined HDM/CS exposure increased the number of inflammatory cells and the levels of HA and OPN in BALF and Th2 cytokine production in mediastinal lymph nodes compared to control groups exposed to phosphate buffered saline (PBS/CS, HDM/Air or PBS/Air. Furthermore, HDM/CS exposure significantly increased goblet cell metaplasia, peribronchial eosinophilia and inflammatory mediators in the lung. CD44 KO mice exposed to HDM/CS had significantly fewer inflammatory cells in BALF, an attenuated Th2 cytokine production, as well as decreased goblet cells and peribronchial eosinophils compared to WT mice. In contrast, the levels of inflammatory mediators were similar or higher than in WT mice.We demonstrate for the first time that the aggravation of pulmonary inflammation upon combined exposure to allergen and an environmental pollutant is CD44-dependent. Data from this murine model of concomitant exposure to CS and HDM might be of importance for smoking allergic asthmatics.

  7. Aggravation of fatigue by steroid therapy in terminally ill patients with cancer.

    Science.gov (United States)

    Matsuo, Naoki; Yomiya, Kinomi

    2014-05-01

    Steroids are commonly used for fatigue relief in terminally ill cancer patients. However, steroid-induced adverse effects including depression, myopathy, and hyperglycemia may contribute to fatigue. We report our experiences with aggravation of fatigue with steroid use in three cases. Case 1 was a 65-year-old man with advanced gastric cancer. He was started on betamethasone (2 mg/d) for fatigue, but the fatigue worsened due to steroid-induced depression. Discontinuation of steroids and initiation of an antidepressant ameliorated the fatigue. Case 2 was a 68-year-old man with advanced lung cancer. He complained of fatigue. Betamethasone (1 mg/d) was started and alleviated the fatigue. However, when the betamethasone dose was increased to 2 mg/d, the fatigue, with muscle weakness and myalgia, worsened due to steroid-induced myopathy. We therefore switched from betamethasone (2 mg/d) to prednisolone (10 mg /d). The fatigue resolved and the patient returned to his previous condition. Case 3 was a 73-year-old man with recurrent bile duct cancer. He also had diabetes mellitus. He developed fatigue, anorexia and fever. We started betamethasone (1.5 mg/d) for these symptoms, but the fatigue and anorexia worsened due to steroid-induced hyperglycemia. Blood glucose rose to 532 mg/dL. Therefore, insulin therapy was started, and the dose of betamethasone was reduced to 0.5 mg/d. His glucose level decreased to less than 320 mg/dL and he recovered from the fatigue while achieving moderate oral intake. In conclusion, the possibility of steroid-induced secondary fatigue in terminally ill cancer patients should be taken into consideration.

  8. Clinical and Experimental Study on Moxibustion in Prevention and Treatment of Primary Liver Cancer%灸法防治原发性肝癌的临床与实验研究进展

    Institute of Scientific and Technical Information of China (English)

    柳杨; 侯中伟; 王朝阳

    2015-01-01

    Primary liver cancer is one of the diseases that have the highest incidence and mortality rate.Moxibustion has a good effect on enhancing immune ability,especially in the treatment of tumor and cancer belonging to accumulation type based on the theory of Traditional Chinese Medicine.This paper summarized related literatures about the clinical and experimental studies on moxibustion in the prevention and treatment of primary liver cancer in recent years.It analyzed the effect of moxibustion in sup-pressing tumor growth,relieving clinical symptoms,improving side effects of chemotherapy and radiotherapy and enhancing immuni-ty.Moxibustion showed definite effect in preventing and curing primary liver cancer.But we need to strengthen the systematical re-search,enhance clinical research quality,and further clarify its mechanism in the future researches.%原发性肝癌是发病率和死亡率最高的恶性肿瘤之一。中医学认为,灸法具有较好的提高免疫力的作用,特别是对于“瘕积聚”类肿瘤疾病有独特的优势。该文从艾灸防治原发性肝癌的临床与实验研究两方面,就近年来有关文献进行总结。通过分析灸法在抑制肿瘤生长,缓解临床症状,改善放化疗不良反应和提高机体免疫力等方面的作用,发现应用灸法防治原发性肝癌疗效确切。建议今后的研究中进一步提高临床研究质量,加强系统化研究以明确作用机制。

  9. Clinical and Experimental Study on Moxibustion in Prevention and Treatment of Primary Liver Cancer%灸法防治原发性肝癌的临床与实验研究进展

    Institute of Scientific and Technical Information of China (English)

    柳杨; 侯中伟; 王朝阳

    2015-01-01

    原发性肝癌是发病率和死亡率最高的恶性肿瘤之一。中医学认为,灸法具有较好的提高免疫力的作用,特别是对于“癥瘕积聚”类肿瘤疾病有独特的优势。该文从艾灸防治原发性肝癌的临床与实验研究两方面,就近年来有关文献进行总结。通过分析灸法在抑制肿瘤生长,缓解临床症状,改善放化疗不良反应和提高机体免疫力等方面的作用,发现应用灸法防治原发性肝癌疗效确切。建议今后的研究中进一步提高临床研究质量,加强系统化研究以明确作用机制。%Primary liver cancer is one of the diseases that have the highest incidence and mortality rate.Moxibustion has a good effect on enhancing immune ability,especially in the treatment of tumor and cancer belonging to accumulation type based on the theory of Traditional Chinese Medicine.This paper summarized related literatures about the clinical and experimental studies on moxibustion in the prevention and treatment of primary liver cancer in recent years.It analyzed the effect of moxibustion in sup-pressing tumor growth,relieving clinical symptoms,improving side effects of chemotherapy and radiotherapy and enhancing immuni-ty.Moxibustion showed definite effect in preventing and curing primary liver cancer.But we need to strengthen the systematical re-search,enhance clinical research quality,and further clarify its mechanism in the future researches.

  10. Approaches to optimize immunosuppression after liver transplantation

    NARCIS (Netherlands)

    Ö. Tapirdamaz (Özlem)

    2014-01-01

    markdownabstract__Abstract__ Since its advent 51 years ago, liver transplantation (LT) has progressed from an experimental treatment to an accepted therapeutic modality that has reversed the gloomy prognosis of end stage liver disease. The great success of LT is for the major part due to calcineuri

  11. Cathepsin K Deficiency Prevents the Aggravated Vascular Remodeling Response to Flow Cessation in ApoE-/- Mice

    OpenAIRE

    Marjo M P C Donners; Bai, Lili; Lutgens, Suzanne P. M.; Wijnands, Erwin; Johnson, Jason; Schurgers, Leon J.; Liu, Cong-Lin; Daemen, Mat; Cleutjens, Kitty B.J.M.; Shi, Guo-Ping; BIESSEN, Erik; Heeneman, Sylvia

    2016-01-01

    Cathepsin K (catK) is a potent lysosomal cysteine protease involved in extracellular matrix (ECM) degradation and inflammatory remodeling responses. Here we have investigated the contribution of catK deficiency on carotid arterial remodeling in response to flow cessation in apoE-/- and wild type (wt) background. Ligation-induced hyperplasia is considerably aggravated in apoE-/- versus wt mice. CatK protein expression was significantly increased in neointimal lesions of apoE-/- compared with w...

  12. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930137 Effects of selective and non-selectiveβ-adrenoreceptor blockers on portal hemody-namics in patients with liver cirrhosis.HUANGTianwei(黄天卫),et al.1st Affili Hosp,DalianMed Coll.Chin J Digest 1992;12(3):145-147.Effects of selective(atenolol)and non-selec-tive(propranolol)β-adrenoreceptor blockerson portal hemodynamics in patients with livercirrhosis were measured by pulsed Doppler du-

  13. Liver in systemic disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Potential causes of abnormal liver function tests include viral hepatitis, alcohol intake, nonalcoholic fatty liver disease, autoimmune liver diseases, hereditary diseases, hepatobiliary malignancies or infection, gallstones and drug-induced liver injury. Moreover, the liver may be involved in systemic diseases that mainly affect other organs. Therefore, in patients without etiology of liver injury by screening serology and diagnostic imaging, but who have systemic diseases, the abnormal liver function test results might be caused by the systemic disease. In most of these patients, the systemic disease should be treated primarily. However, some patients with systemic disease and severe liver injury or fulminant hepatic failure require intensive treatments of the liver.

  14. The protective effects of OLA-PENa on experimental liver injury in rats%齐酞酸钠对大鼠实验性肝损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    宛蕾; 陈秀芬; 蒋朝晖

    1998-01-01

    To investigate the protective effects of OLA-PENa on experimental hepatic injury in rats and compare it with OLA in the dose-response relationships. METHODS: Biochemical indexes and histopathological examination of hepatic injury in rats caused by toxicant chemicals [D-galactosamine (D-Galn) and CCl4] were determined. RESULTS: OLA-PENa obviously inhibited the rising of serum alanine transaminase (ALT) caused by D-Galn and CCl4 and dramatically decreased liver fat storage as well in a dose-dependent manner. Histopathological examination showed that OLA-PENa can evidently alleviate the condition of the degeneration of hepatic cells and that of necrosis. CONCLUSION: The protective effects of OLA-PENa on experimental liver injury in rats, all the mentioned effects, are more powerful than those of OLA with the same dosage.%目的:研究齐酞酸钠对大鼠实验性肝损伤的保护作用,并与齐墩果酸进行量-效比较。方法:采用化学毒物D-氨基半乳糖和四氯化碳致大鼠肝脏损伤,测定生化指标及观察病理组织学改变。结果:齐酞酸钠呈剂量依赖性地明显降低D-氨基半乳糖、四氯化碳引起的大鼠血清丙氨酸转移酶(ALT)增高;显著减轻肝脏中脂肪蓄积;病理组织学检查齐酞酸钠明显减轻肝细胞的变性和坏死。结论:齐酞酸钠对大鼠实验性肝损伤有明显的保护作用,在同等剂量下上述作用优于齐墩果酸。

  15. Experimental on Antibody Targeting Liver Cancer Stem Cell Treatment%肝癌干细胞抗体靶向治疗的实验

    Institute of Scientific and Technical Information of China (English)

    孙力超; 赵璇; 孙立新; 遇珑; 杨治华; 冉宇靓

    2011-01-01

    Objective To study the biological characteristics and function of the anti- hepatocellular carcinoma cancer stem cells (HCC-CSC) monoclonal antibody 15B7 in vivo and in vitro, and to investigate whether the targeting liver stem cells can inhibit recurrence, spontaneous lung metastasis and prolong the survival of tumor-bearing mice. Methods Monoclonal antibody 15B7 which could recognize HCC-CSC was identified by two-color immunofluorescence, two-color flow cytometry and subcutaneous tumor formation assay. CD133+ phenotype cells were sorted from BEL7402 cell lines by the flow cytometry and cultured in serum free medium. The function of 15B7 was identified by CCK8 cell proliferation, invasion assay, migration assay and flow cytometry. The inhibition of implanted tumor growth and spontaneous lung metastasis of monoclonal antibody 15B7 were studied by tumor treatment experiments and the survival of mice was also observed. The antigen of 15B7 was identified by western blotting. Results The results of two-color immunofluorescence and two-color flow cytometry showed that monoclonal antibody 15B7 could recognized cells which also were partly co-stained with ESA or CD133. 15B7+ or ESA+ cells or CD133+ cells sorted by flow cytometry could form mammospheres after serum-free suspension culture. 1 × 104 15B7+ cells were inoculated into the nude mice and developed visible tumors in 2 months. In vitro functional experiments showed that monoclonal antibody 15B7 could inhibit the proliferation, migration and invasion of CD133+ cells, and the inhibition rates was 13. 8%, 15. 7% and 30. 9%, respectively. Furthermore, CD133+ cells incubated with monoclonal antibody 15B7 were induced G1 phase arrest.Animal experiment revealed that monoclonal antibody 15B7 significantly inhibited tumor growth by 60. 5%. Conclusion 15B7 not only inhibited tumor growth. The results indicated that targeting cancer stem cell antibody therapy had significant advantages and monoclonal antibody 15B7

  16. The influence of hypothyroidism on liver regeneration: an experimental study in rats A influência do hipotireoidismo na regeneração hepatica: estudo experimental em ratos

    Directory of Open Access Journals (Sweden)

    Maria de Lourdes Pessole Biondo-Simões

    2007-01-01

    Full Text Available BACKGROUND: The influence of hypothyroidism in liver regeneration has been a controversial opinions. PURPOSE: The aim of this study is to identify the relationship between hypothyroidism and liver regeneration in rats. METHODS: Forty male Wistar rats divided into two groups of 20 specimens each. One group (C consisted of euthyroid rats, and the other (H of hypothyroid rats. All the animals were anesthetized with xylazine and ketamine and subjected to a longitudinal incision in the anterior cervical region. The thyroid was completely resected in group H and left intact in group C. Ten days after the first surgery, both groups of rats were weighed and submitted to partial hepatectomy, in which the left lateral and median lobes were resected and weighed. Examinations were carried out after 24 hours and, on day 7, using 3 methods: KWON et al.'s formula to identify increase in volume; mitotic figure count in five fields; and the percentage of PCNA-positive nuclei in five fields. RESULTS: Using KWON's formula, the regeneration rate for Group C after 24 hours was 58.49% whereas that for Group H was 50.42% (p=0.0165. After 7 days, the regeneration rate for Group C was 93.04% and Group H 93.74% (p=0.2165. The average number of mitotic figures after 24 hours was 14 ± 1.5 for Group C and 9.8 ± 2.2 for Group H (p=0,00016. After 7 days the corresponding figures were 5.4 ± 1.1 and 5.1 ± 1.2 (p=0,6343. The average number of PCNA-positive nuclei after 24 hours was 13.55 ± 3.84 in Group C and 7.7 ± 2.11 in Group H (p =0,0006. The corresponding figures after 7 days were 3.5 ± 2.39 for Group C and 4.11 ± 1.90 for Group H (p>0.05. CONCLUSION: We conclude that hypothyroidism in rats causes a delay in hepatic regeneration in the first 24 hours, but that after seven days the rate of regeneration is equal to that in euthyroid rats.BACKGROUND: A influência do hipotireoidismo na regeneração hepatica tem opiniões controvérsas. OBJETIVO: Identificar a rela

  17. The history of liver transplantation in Turkey.

    Science.gov (United States)

    Moray, Gökhan; Arslan, Gülnaz; Haberal, Mehmet

    2014-03-01

    Liver transplantation is the definitive treatment for end-stage liver diseases. The first successful liver transplant was performed in the United States by Thomas Starzl in 1967. The first successful solid organ transplant in Turkey was a living-related kidney transplant performed by Dr. Haberal in 1975. After much effort by Dr. Haberal, the Turkish parliament enacted a law about organ transplantation in 1979. After clinical and experimental studies, the first liver transplant in Turkey was performed by Dr. Haberal in 1988. The first successful partial living-donor liver transplant in children in Turkey was performed by the same team on March 15, 1990. On April 24, 1990, the first living-donor liver transplant was performed on a child in Turkey using a left lateral segment by Dr. Haberal and coworkers. On May 16, 1992, Dr. Haberal performed a simultaneous living-donor liver and kidney transplantation to an adult from the same donor. There currently are 30 liver transplantation centers in Turkey. According to data from the Ministry of Health, there presently are 2065 patients in Turkey who are waiting for a liver transplantation. From January 2002 to June 2013, there were 6091 liver transplants performed in Turkey (4020 living-donor [66% ] and 2071 deceased donor liver transplants [34% ]). From January 2011 to June 2013, there were 2514 patients who had liver transplants in Turkey, and 437 patients (17%) died. The number of liver transplants per year in Turkey reached 1000 transplants in 2012 and more than 1150 transplants in 2013 (15.1/million/y). Therefore, Turkey has one of the highest volumes of liver transplantation per population worldwide, with 90% survival within 1 year after transplantation.

  18. Liver transplant for cholestatic liver diseases.

    Science.gov (United States)

    Carrion, Andres F; Bhamidimarri, Kalyan Ram

    2013-05-01

    Cholestatic liver diseases include a group of diverse disorders with different epidemiology, pathophysiology, clinical course, and prognosis. Despite significant advances in the clinical care of patients with cholestatic liver diseases, liver transplant (LT) remains the only definitive therapy for end-stage liver disease, regardless of the underlying cause. As per the United Network for Organ Sharing database, the rate of cadaveric LT for cholestatic liver disease was 18% in 1991, 10% in 2000, and 7.8% in 2008. This review summarizes the available evidence on various common and rare cholestatic liver diseases, disease-specific issues, and pertinent aspects of LT.

  19. RGD-tagged helical rosette nanotubes aggravate acute lipopolysaccharide-induced lung inflammation

    Directory of Open Access Journals (Sweden)

    Suri SS

    2011-12-01

    Full Text Available Sarabjeet Singh Suri1, Steven Mills1, Gurpreet Kaur Aulakh1, Felaniaina Rakotondradany2, Hicham Fenniri2, Baljit Singh11Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon; 2National Institute for Nanotechnology and Department of Chemistry, Edmonton, CanadaAbstract: Rosette nanotubes (RNT are a novel class of self-assembled biocompatible nanotubes that offer a built-in strategy for engineering structure and function through covalent tagging of synthetic self-assembling modules (G∧C motif. In this report, the G∧C motif was tagged with peptide Arg-Gly-Asp-Ser-Lys (RGDSK-G∧C and amino acid Lys (K-G∧C which, upon co-assembly, generate RNTs featuring RGDSK and K on their surface in predefined molar ratios. These hybrid RNTs, referred to as Kx/RGDSKy-RNT, where x and y refer to the molar ratios of K-G∧C and RGDSK–G∧C, were designed to target neutrophil integrins. A mouse model was used to investigate the effects of intravenous Kx/RGDSKy-RNT on acute lipopolysaccharide (LPS-induced lung inflammation. Healthy male C57BL/6 mice were treated intranasally with Escherichia coli LPS 80 µg and/or intravenously with K90/RGDSK10-RNT. Here we provide the first evidence that intravenous administration of K90/RGDSK10-RNT aggravates the proinflammatory effect of LPS in the mouse. LPS and K90/RGDSK10-RNT treatment groups showed significantly increased infiltration of polymorphonuclear cells in bronchoalveolar lavage fluid at all time points compared with the saline control. The combined effect of LPS and K90/RGDSK10-RNT was more pronounced than LPS alone, as shown by a significant increase in the expression of interleukin-1ß, MCP-1, MIP-1, and KC-1 in the bronchoalveolar lavage fluid and myeloperoxidase activity in the lung tissues. We conclude that K90/RGDSK10-RNT promotes acute lung inflammation, and when used along with LPS, leads to exaggerated immune response in the lung.Keywords: RGD peptide, helical rosette

  20. Loss of p120 catenin aggravates alveolar edema of ventilation induced lung injury

    Institute of Scientific and Technical Information of China (English)

    DAI Chen-yang; DAI Guo-feng; SUN Yu; WANG Yue-lan

    2013-01-01

    Background p120 catenin (p120ctn) is an adheren junction protein that regulates barrier function,but its role has not been explored in alveolar edema induced by ventilation.We measured stretch-induced cell gap formation in MLE 12 cells due to the loss of p120.We hypothesized that alveolar permeability was increased by high lung inflation associated with alveolar epithelia cell tight junctions being destroyed,which resulted from the loss of p120.Methods Cultured MLE12 cells were subjected to being stretched or un-stretched (control) and some cells were pretreated with pp2 (c-src inhibitor).After the end of stretching for 0,1,2,and 4 hours,the cells were lysed,and p120 expression and c-src activation was determined by Western blotting analysis.In vivo,SD rats were taken to different tidal volumes (Vt 7 ml/kg or 40 ml/kg,PEEP=0,respiratory rate 30-40 betas/min) for 0,1,2,and 4 hour and some were pretreated with pp2,and alveolar edema was calculated.Rerults It was found that p120 expression was reduced and c-src activation increased in a time-dependent and strain-dependent manner due to cyclic-stretch of the alveolar epithelial cells.These changes could be reversed by inhibition of c-src.We obtained similar changes in rats when they were subjected to large tidal volumes and the alveolar edema increased more than in rats in the low Vt group.Pretreated the rats with inhibition of c-src had less pulmonary edema induced by the high tidal volume ventilation.Conclusions Cyclic stretch MLE 12 cells induced the loss of p120 and may be the same reason by high tidal volume ventilation in rats can aggravate alveolar edema.Maintenance of p120 expression may be a novel therapeutic strategy for the prevention and treatment of ventilation induced lung injury (VILI).

  1. [Liver resection by water jet].

    Science.gov (United States)

    Horie, T

    1989-01-01

    Major problem in resecting liver parenchyma is how to control the bleeding. Recently, resection of the liver by water jet has been reported. So, experimental and clinical studies were performed to investigate the usefulness of the water jet equipment. Ten pigs weighing around 17kg were used. The optimal pressure to resect the porcine liver was 7 to 15kg/cm2. By 4 weeks the cut surface was covered with fibrous capsule. Portal angiography showed no abnormality in the resected area. The water jet was also used in 30 human operations. The optimal pressure was 12 to 18kg/cm2 for non cirrhotic liver and 15 to 20kg/cm2 for cirrhotic liver. The surface immediately after jet cutting was more smooth than that of CUSA and histologically there was slight bleeding and necrosis. The volume of blood loss during dissection was not different between water jet group and CUSA group. No significant changes were found in the laboratory data. These results suggest that water jet is as useful as CUSA for cutting the liver parenchyma.

  2. Hepatic venous outflow obstruction after piggyback liver transplantation by an unusual mechanism: Report of a case

    Institute of Scientific and Technical Information of China (English)

    Simon Siu-Man Ng; Simon Chun-Ho Yu; Janet Fung-Yee Lee; Paul Bo-San Lai; Wan-Yee Lau

    2006-01-01

    Hepatic venous outflow obstruction after piggyback liver transplantation is a very rare complication. An unusual mechanism aggravating it is reported. A 33-year-old man with end-stage hepatitis B liver cirrhosis underwent a piggyback orthotopic liver transplantation using a fullsize cadaveric graft. Two months after transplantation,he developed gross ascites refractory to maximal diuretic therapy. Doppler ultrasound showed patent portal and hepatic veins. Serial computed tomography scans revealed a hypoperfused right posterior segment of the liver which subsequently underwent atrophy. Hepatic venography demonstrated a high-grade stenosis with an element of torsion of venous drainage at the anastomosis. The stenosis was successfully treated with repeated percutaneous balloon angioplasty. The patient remained asymptomatic six months afterwards with complete resolution of ascites and peripheral edema. We postulate that liver allograft segmental hypoperfusion and atrophy may aggravate or result in a hepatic venous outflow problem by the mechanism of torsion effect. Percutaneous balloon angioplasty is a safe and effective treatment modality for anastomotic stenosis.

  3. Liver Disease and IBD

    Science.gov (United States)

    ... Home > Resources > Liver Disease and IBD Go Back Liver Disease and IBD Email Print + Share Several complications ... be necessary to make the definitive diagnosis. FATTY LIVER DISEASE (HEPATCI STEATOSIS) This is the most common ...

  4. Pyogenic liver abscess

    Science.gov (United States)

    Liver abscess; Bacterial liver abscess ... There are many possible causes of liver abscesses, including: Abdominal infection, such as appendicitis , diverticulitis , or a perforated bowel Infection in the blood Infection of the bile draining tubes ...

  5. Liver Function Tests

    Science.gov (United States)

    ... food, store energy, and remove poisons. Liver function tests are blood tests that check to see how well your liver ... hepatitis and cirrhosis. You may have liver function tests as part of a regular checkup. Or you ...

  6. Amebic liver abscess

    Science.gov (United States)

    Hepatic amebiasis; Extraintestinal amebiasis; Abscess - amebic liver ... Amebic liver abscess is caused by Entamoeba histolytica. This parasite causes amebiasis , an intestinal infection that is also called ...

  7. Liver regeneration in nonalcoholic fatty liver disease

    OpenAIRE

    Aldo Lagomarsino

    2012-01-01

    Steatosis is the accumulation of fat in hepatocytes, which may be the result of liver regeneration or pathological processes such as alcoholic and nonalcoholic fatty liver disease. Despite its importance, in both cases the exact mechanism that prevails in fatty liver regeneration is poorly understood. Previous studies have shown that patients with fatty liver express dispar regeneration, possibly due to the accumulation of reactive oxygen species generated by inflammatory processes caused by ...

  8. Gene therapy of liver cancer

    Institute of Scientific and Technical Information of China (English)

    Ruben Hernandez-Alcoceba; Bruno Sangro; Jesus Prieto

    2006-01-01

    The application of gene transfer technologies to the treatment of cancer has led to the development of new experimental approaches like gene directed enzyme/prodrug therapy (GDEPT), inhibition of oncogenes and restoration of tumor-suppressor genes. In addition,gene therapy has a big impact on other fields like cancer immunotherapy, anti-angiogenic therapy and virotherapy.These strategies are being evaluated for the treatment of primary and metastatic liver cancer and some of them have reached clinical phases. We present a review on the basis and the actual status of gene therapy approaches applied to liver cancer.

  9. Immunological and molecular basis of nonalcoholic steatohepatitis and nonalcoholic fatty liver disease.

    Science.gov (United States)

    Radwan, Mohamed M; Radwan, Basil M; Nandipati, Kalyana C; Hunter, William J; Agrawal, Devendra K

    2013-08-01

    The prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is rising worldwide with the increasing incidence of obesity, Type 2 diabetes mellitus and metabolic syndrome. NASH is currently one of the most common indications of liver transplantation in the United States. The immune system plays a major role in the pathogenesis of NAFLD/NASH. The metabolic changes, associated with obesity and metabolic syndrome, induce immunological responses resulting in NAFLD and further aggravation of the metabolic derangement in a feed-forward loop. Genetic and endocrine factors modulate the immunological and metabolic responses and determine the pathophysiological features of NAFLD. Histologically, NAFLD is a spectrum that ranges from simple hepatic steatosis to severe steatohepatitis, liver cirrhosis and/or hepatocellular carcinoma. Liver cirrhosis and hepatocellular carcinoma are responsible for the morbidity and mortality of the disease. This article is a critical evaluation of our current knowledge of the immunological and molecular basis of the disease.

  10. Getting a New Liver: Facts about Liver Transplants

    Science.gov (United States)

    ... 2002 December 2006 March 2012 Getting A New Liver Facts About Liver Transplants American Society of Transplantation 1120 Route 73, ... views of the Society. _________________________________________________________________ 1 Getting a New Liver Facts About Liver Transplants A liver transplant is ...

  11. Alcoholic liver disease: the gut microbiome and liver cross talk.

    Science.gov (United States)

    Hartmann, Phillipp; Seebauer, Caroline T; Schnabl, Bernd

    2015-05-01

    Alcoholic liver disease (ALD) is a leading cause of morbidity and mortality worldwide. Alcoholic fatty liver disease can progress to steatohepatitis, alcoholic hepatitis, fibrosis, and cirrhosis. Patients with alcohol abuse show quantitative and qualitative changes in the composition of the intestinal microbiome. Furthermore, patients with ALD have increased intestinal permeability and elevated systemic levels of gut-derived microbial products. Maintaining eubiosis, stabilizing the mucosal gut barrier, or preventing cellular responses to microbial products protect from experimental ALD. Therefore, intestinal dysbiosis and pathological bacterial translocation appear fundamental for the pathogenesis of ALD. This review highlights causes for intestinal dysbiosis and pathological bacterial translocation, their relationship, and consequences for ALD. We also discuss how the liver affects the intestinal microbiota.

  12. A study of human liver ferritin and chicken liver and spleen using Moessbauer spectroscopy with high velocity resolution

    Energy Technology Data Exchange (ETDEWEB)

    Oshtrakh, M. I., E-mail: oshtrakh@mail.utnet.ru [Ural State Technical University-UPI, Faculty of Physical Techniques and Devices for Quality Control (Russian Federation); Milder, O. B.; Semionkin, V. A. [Ural State Technical University-UPI, Faculty of Experimental Physics (Russian Federation)

    2008-01-15

    Lyophilized samples of human liver ferritin and chicken liver and spleen were measured at room temperature using Moessbauer spectroscopy with high velocity resolution. An increase in the velocity resolution of Moessbauer spectroscopy permitted us to increase accuracy and decrease experimental error in determining the hyperfine parameters of human liver ferritin and chicken liver and spleen. Moessbauer spectroscopy with high velocity resolution may be very useful for revealing small differences in hyperfine parameters during biomedical research.

  13. 严重暴力犯罪概念解析%Analyzing the Concept of Aggravated Violent Crime

    Institute of Scientific and Technical Information of China (English)

    何册辉

    2012-01-01

      Compared with a traditional violent crime, an aggravated violent crime has endangered public security, which is its essential characteristic. The article starts from confusing terms like“a violent crime”, “an aggravated violent crime”, “an unexpected public event” and “a terrorist attack event”, distinguishing each connotation and nature, and then proposes that the nature of an unexpected event should be defined with the combination of the behavioral means and the endangering public security. The fundamental difference between an aggravated violent crime and a common violent crime lies in the factor of with or without “willful and malicious destruction, and endangering public security”. Aggravated violent crimes, as one of the most serious in unexpected events, have to be dealt immediately with special means rather than relying on the sole way through criminal punishment.%  与传统暴力犯罪相比,严重暴力犯罪已经危害公共安全,这是其本质特征。文章从“暴力犯罪”、“严重暴力犯罪”、“突发公共事件”、“恐怖袭击事件”等易混淆的概念入手,从认识层面理清各自内涵属性,提出应从行为手段与危害公共安全二者的结合来界定突发事件的性质,认为是否内含“人为恶意破坏、危害公共安全”要素是严重暴力犯罪与一般暴力犯罪的根本差别。严重暴力犯罪案件作为突发事件中性质最为严重的一种,其发生、发展的控制不能寄刑罚手段一途,须动用特别手段紧急处置。

  14. Liver cirrhosis and fatty liver

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930537 Preliminary report on portal hyperten-tion in liver cirrhosis treated by transjugular in-trahepatic portosystemic stent shunt(analysis of8 cases).XU Ke(徐克),et al.Dept Radiol,lst Hosp,China Med Univ,Shenyang,110001.Chin J Radiol 1993;25(5):294—297.Transjugular intrahepatic portosystemic stentshunt(TIPPS)was performed in 8 cases of livercirrhosis with portal hypertention.Moderate orsevere hemorrhage from gastroesophageal variceshad happened in all patients for 2~5 times beforTIPSS.The average pressure of portal veindropped from 3.80±0.50kPa to 2.58±0.26kPa.The diameter of the shunt established be-tween portal and hepatic veins was 10~12mm.Gastrointestinal bleeding and ascites were effec-

  15. The Protective Effects of Curcumin on Experimental Acute Liver Lesion Induced by Intestinal Ischemia-Reperfusion through Inhibiting the Pathway of NF-κB in a Rat Model

    Directory of Open Access Journals (Sweden)

    Zhe Fan

    2014-01-01

    Full Text Available Objective. In this study, we investigated the protective effect and mechanism of curcumin on a rat model of intestinal ischemia/reperfusion (I/R, which induces an acute liver lesion. Methods. Curcumin was injected into rats in the curcumin groups through left femoral vein. The same volume of vehicle (0.9% normal saline was injected into sham and I/R groups. Blood and liver tissue were gathered for serological and histopathological determination. Results. Intestinal I/R led to severe liver injury manifested as a significant increase in serum AST and ALT levels; all of those were reduced by treatment with curcumin. Simultaneously, the activity of SOD in liver decreased after intestinal I/R, which was increased by curcumin treatment. On the other hand, curcumin reduced MPO activity of liver tissue, as well as serum IL-6 and TNF-α levels observably. This is in parallel with the decreased level of liver intercellular cell adhesion molecule-1 (ICAM-1 and nuclear factor-κB (NF-κB expression. Conclusion. Our findings suggest that curcumin treatment attenuates liver lesion induced by intestinal I/R, attributable to the antioxidative and anti-inflammatory effect via inhibition of the NF-κB pathway.

  16. Oral exposure to low-dose bisphenol A aggravates testosterone-induced benign hyperplasia prostate in rats.

    Science.gov (United States)

    Wu, Jian-Hui; Jiang, Xiu-Rong; Liu, Gui-Ming; Liu, Xiang-Yun; He, Gui-Lin; Sun, Zu-Yue

    2011-10-01

    The declining level of androgen during aging, associated with an inclining level of estrogen, has been hypothesized to be important in the development of benign prostatic hyperplasia (BPH). Within physiologic range, increasing estrogen levels can stimulate prostate to develop and permanently increase prostate size. As an estrogenic endocrine disruptor, bisphenol A (BPA) might be stimulatory to prostate development. We further hypothesized that low dose BPA could induce hyperplasia prostate to proliferate and aggravate the symptom of BPH in male SD rats. BPH was induced by testosterone and then treated with BPA (10, 30, or 90 μg/kg, i.g., daily), 17β-estradiol (E(2); 50.0 μg/kg, s.c., daily), or vehicle for 4 weeks. We found that weight and volume in rats treated with low dose BPA (10 μg/kg) was higher than that of model control, and BPA significantly increased the relative weight of prostate (p prostate lobes, BPA 10 μg/kg/day significantly increased relative weight of ventral prostate (VP), weight and relative weight of dorsolateral prostate (DLP) (p prostate-specific antigen level. E(2) treatment also showed an obvious effect on relative weight of VP and DLP, HEC, and hormone levels. We concluded that environment exposure to low dose of BPA may induce prostate to proliferate and aggravate testosterone-induced benign hyperplasia prostate in rats.

  17. Oral Candida as an aggravating factor of mucositis Induced by radiotherapy; Candida Oral como fator agravante da mucosite radioinduzida

    Energy Technology Data Exchange (ETDEWEB)

    Simoes, Cristiane Araujo; Castro, Jurema Freire Lisboa de; Cazal, Claudia [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de odontologia

    2011-07-01

    Antineoplastic treatment induces some undesirable consequences in head and neck cancer patients. Often, the emergence of major clinical manifestations, such as oral mucositis, results in temporary interruption of the treatment, decreasing the patients' quality of life, and increasing hospital costs. Radio-induced or chemo-induced oral mucositis is possibly aggravated by opportunist fungal infections, which turn the mucositis more resistant to the conventional treatments. Objective: this study aims to identify the presence of Candida sp. as a possible aggravating factor of oral mucositis in patients with head and neck cancer under antineoplastic treatment. Method: all patients with radio- or chemo-induced oral mucositis from the Cancer Hospital of Pernambuco, treated between October 2008 and April 2009, were selected for the study. The prevalence of Candida sp was measured through the cytological analysis of oral mucosa in patients with oral mucositis. The fungal presence was correlated with the mucositis severity. Results: the results showed a positive association between fungal colonization and more several lesions (degrees III and IV of mucositis). Conclusion: The outcomes shown may contribute to a solution for unconventional mucosites, which do not respond to the usual treatment. (author)

  18. Long-term management of sevelamer hydrochloride-induced metabolic acidosis aggravation and hyperkalemia in hemodialysis patients.

    Science.gov (United States)

    Sonikian, Macroui; Metaxaki, Polyxeni; Iliopoulos, Anastasios; Marioli, Stamatia; Vlassopoulos, Dimosthenis

    2006-01-01

    Sevelamer hydrochloride use in hemodialysis patients is complicated by metabolic acidosis aggravation and hyperkalemia. Rare reports about a short-term correction of this complication have been published. The current authors investigated the long-term correction of metabolic acidosis and hyperkalemia in sevelamer hydrochloride-treated patients at doses adequate to achieve serum phosphate levels within K/DOQI recommendations. The authors followed 20 hemodialysis patients for 24 months in an open-label prospective study. The dialysate bicarbonate concentration was increased stepwise to a maximum 40 mEq/L and adjusted to reach patient serum bicarbonate levels of 22 mEq/L, according to K/DOQI recommendations. Laboratory results for serum bicarbonate, potassium, calcium, phosphate, albumin, alkaline phosphatase, iPTH, cholesterol (HDL-LDL), triglycerides, Kt/V, systolic-diastolic arterial pressure were recorded. Sevelamer hydrochloride-induced metabolic acidosis aggravation and hyperkalemia in hemodialysis patients were corrected, on the long-term, by an increase in dialysate bicarbonate concentration. Further improvement in bone biochemistry was noted with this adequate acidosis correction and parallel sevelamer hydrochloride administration, in sufficiently large doses to achieve K/DOQI phosphate recommendations.

  19. Immune mediated liver failure

    OpenAIRE

    Wang, Xiaojing; Ning, Qin

    2014-01-01

    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capac...

  20. Appropriateness of Liver Biopsy

    OpenAIRE

    Thierry Poynard; Vlad Ratziu; Pierre Bedossa

    2000-01-01

    This review aims to discuss the appropriateness of liver biopsy in two frequent liver diseases, hepatitis C and alcoholic liver disease. The medical literature, published between 1965 and 1999, was reviewed by using MEDLINE. Only 0.1% of the publications were devoted specifically to the appropriateness of liver biopsy. Not all studies observed a significant agreement among doctors on the decision to use liver biopsy. Therefore, there is a possibility that hepatologists have significant, heter...

  1. Ferrous sulfate, but not iron polymaltose complex, aggravates local and systemic inflammation and oxidative stress in dextran sodium sulfate-induced colitis in rats

    Directory of Open Access Journals (Sweden)

    Toblli JE

    2015-05-01

    Full Text Available Jorge E Toblli, Gabriel Cao, Margarita Angerosa Laboratory of Experimental Medicine, Hospital Alemán, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina Background and aims: Iron deficiency is common in inflammatory bowel disease, yet oral iron therapy may worsen the disease symptoms and increase systemic and local oxidative stress. The aim of this study was to compare the effects of oral ferrous sulfate and iron polymaltose complex on inflammatory and oxidative stress markers in colitic rats.Methods: Animals were divided into four groups with ten animals each. Rats of three groups received dextran sodium sulfate to induce colitis and animals of two of these groups received 5 mg iron/kg of body weight a day, as ferrous sulfate or iron polymaltose complex, for 7 days. Gross colon anatomy, histology of colon and liver, stainings of L-ferritin, Prussian blue, hepcidin, tumor necrosis factor-α, and interleukin-6, as well serum levels of liver enzymes, inflammatory markers, and iron markers, were assessed.Results: Body weight, gross anatomy, crypt injury and inflammation scores, inflammatory parameters in liver and colon, as well as serum and liver hepcidin levels were not significantly different between colitic animals without iron treatment and colitic animals treated with iron polymaltose complex. In contrast, ferrous sulfate treatment caused significant worsening of these parameters. As opposed to ferrous sulfate, iron polymaltose complex caused less or no additional oxidative stress in the colon and liver compared to colitic animals without iron treatment.Conclusion: Iron polymaltose complex had negligible effects on colonic tissue erosion, local or systemic oxidative stress, and local or systemic inflammation, even at high therapeutic doses, and may thus represent a valuable oral treatment of iron deficiency in inflammatory bowel disease. Keywords: preclinical, oral iron treatment, tolerability, colonic tissue erosion

  2. HIBADH Plays an Important Role in the Course of Liver Cell Necrosis

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    Objective To observe the biological function of human 3-hydroxyisobutyrate dehydrogenase (HIBADH). Methods Human 3-hydroxyisobutyrate dehydrogenase (HIBADH, 3-hydroxy-2-methyl propanoate: NAD+oxidoreductase) recombinant protein was expressed inE. coli BL21,and puriifed by Ni+ column. The special antisera was obtained from rabbits immunized by this purified antigen. On the distribution of HIBADH, it was found that HIBADH over-expressed in the injured liver cells when serious hepatitis occurred. The phenomenon was conifrmed in the animal models of SD rats with acute liver cell injury induced by CCl4, but this phenomenon did not exist in the models induced by endotoxin combined with galactosamine. Further more, HIBADH’s overexpression in liver cells will induce cell necrosis through the pathway of oxidative stress. Results When the liver cells injured by drug or other chemical materials, HIBADH will be compensationally over-expressed for the deifciency of energy, so liver cells can make enough ATP through brand-chain amino acid catabolism. However, the overexpression of HIBADH will be harmful for liver cells through the product of much more active oxygens which will induce the cell necrosis. Conclusions HIBADH over-expression is a signal of the liver cell metabolism injury, and it can aggravate the liver cell injury through oxidative stress.

  3. Using multiphoton fluorescence lifetime imaging to characterize liver damage and fluorescein disposition in liver in vivo

    Science.gov (United States)

    Thorling, Camilla A.; Studier, Hauke; Crawford, Darrell; Roberts, Michael S.

    2016-03-01

    Liver disease is the fifth most common cause of death and unlike many other major causes of mortality, liver disease rates are increasing rather than decreasing. There is no ideal measurement of liver disease and although biopsies are the gold standard, this only allows for a spot examination and cannot follow dynamic processes of the liver. Intravital imaging has the potential to extract detailed information over a larger sampling area continuously. The aim of this project was to investigate whether multiphoton and fluorescence lifetime imaging microscopy could detect early liver damage and to assess whether it could detect changes in metabolism of fluorescein in normal and diseased livers. Four experimental groups were used in this study: 1) control; 2) ischemia reperfusion injury; 3) steatosis and 4) steatosis with ischemia reperfusion injury. Results showed that multiphoton microscopy could visualize morphological changes such as decreased fluorescence of endogenous fluorophores and the presence of lipid droplets, characteristic of steatosis. Fluorescence lifetime imaging microscopy showed increase in NADPH in steatosis with and without ischemia reperfusion injury and could detect changes in metabolism of fluorescein to fluorescein monoglurcuronide, which was impaired in steatosis with ischemia reperfusion injury. These results concluded that the combination of multiphoton microscopy and fluorescence lifetime imaging is a promising method of assessing early stage liver damage and that it can be used to study changes in drug metabolism in the liver as an indication of liver disease and has the potential to replace the traditional static liver biopsy currently used.

  4. Electrochemotherapy for rat implanted liver tumour

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ The most common interventional therapies for liver cancer at present include transcatheter hepatic arterial chemoembolization (TACE),1 percutaneous ethanol injection2 and radiofrequency ablation,3 but all these therapies have some intrinsic disadvantages. Since the advent of electrochemo- therapy (EChT), it has been accepted as a safe and effective therapy for malignant tumors4,5 There are only a few experimental studies reporting the use of EChT in the treatment of liver cancer in the foreign medical literature.6-8 However, there have been some clinical studies, and even fewer reports of experimental studies on EChT for liver cancer in China. We used a rat implanted liver cancer animal model to monitor changes in tumour size, tumour necrosis, cellular apoptosis, expression of peripheral immunological markers (IL-2, sIL-2R, IL-6 and TNF-α) and survival.

  5. Aggravation by vanadium of magnesium deficiency in STZ-induced diabetic rats.

    Science.gov (United States)

    Bermúdez-Peña, M C; López-Chaves, C; Llopis, J; Guerrero-Romero, F; Montes-Bayón, M; Sanz-Medel, A; Sánchez-González, C

    2013-01-01

    This study examined changes in the metabolism of magnesium (Mg), and related serum parameters, following treatment with vanadium (V) in streptozotocin-diabetic rats. Over a period of five weeks, four groups were examined: control, diabetic, diabetic-treated with 1 mg V/day or 3 mg V/day. The V was supplied in drinking water as bis(maltolato)oxovanadium(IV). The Mg levels were measured in food, faeces, urine, serum, muscle, kidney, liver, spleen, heart and femur. Albumin, uric acid, urea, total-cholesterol, LDL-cholesterol, triglycerides, aspartate-aminotransferase and alkaline-phosphatase were determined in serum. In the diabetic group, Mg retained and Mg content in serum and femur decreased, while levels of uric acid, urea, total-cholesterol, LDL-cholesterol, triglycerides and alkaline-phosphatase and aspartate-aminotransferase activity increased compared with control rats. In the diabetic group treated with 1 mg V/day, Mg retained, serum levels of Mg, urea and triglycerides, and alkaline-phosphatase activity remained unchanged, while levels of uric acid, total-cholesterol and LDL-cholesterol increased and the Mg content in femur and aspartate-aminotransferase activity decreased compared with the diabetic untreated group. In the diabetic rats treated with 3 mg V/day, food intake and glycaemia were normal. In this group, Mg content in serum, kidney and femur, levels of urea and aspartate-aminotransferase and alkaline-phosphatase activity decreased, whereas LDL-cholesterol increased, uric acid and total-cholesterol levels remained unchanged in comparison with untreated diabetic rats. In conclusion, although treatment with 3 mg V/day normalised the glycaemia, the hypomagnesaemia and tissue depletion of Mg seen in the diabetic rats, caused by the treatment with V, could have partially contributed to the fact that V did not normalise other serum parameters altered by the diabetes.

  6. Shift work aggravates metabolic syndrome development among early-middle-aged males with elevated ALT

    Institute of Scientific and Technical Information of China (English)

    Yu-Cheng Lin; Tun-Jen Hsiao; Pau-Chung Chen

    2009-01-01

    AIM: To examine whether shift work accelerates metabolic syndrome (MetS) development among early middle- aged males with elevated alanine aminotransferase (e-ALT).METHODS: A retrospective, observational followup study on MetS development at a 5-year interval was conducted using health examination data. Nine hundred and ninety six male employees not fulfilling MetS criteria at screening were enrolled. Age, MetScomponents,liver enzymes, serological markers for viral hepatitis, abdominal ultrasound, insulin resistance status, lifestyles, and workplace factors were analyzed.RESULTS: The prevalence of elevated serum ALT (> 40 U/L, e-ALT) at baseline was 19.1%. There were 381 (38.3%) workers with long-term exposures to daynight rotating shift work (RSW). 14.2% of subjects developed MetS during follow-up. After 5 years, the workers with e-ALT had significantly unfavorable changes in MetS-components, and higher rates of MetS development, vs subjects with normal baseline ALT levels. Workers with both baseline e-ALT and 5-year persistent RSW (pRSW) exposure had the highest rate of MetS development. Also, e-ALT-plus-pRSW workers had a significant increase in MetS-components at follow-up, compared with the other subgroups. After controlling for potential confounders, e-ALT-plus-pRSW workers posed a significant risk for MetS development (odds ratio, 2.7; 95% confidence interval, 1.4-5.3, vs workers without baseline e-ALT nor pRSW). CONCLUSION: We suggest that all early middleaged male employees with e-ALT should be evaluated and managed for MetS. Particularly in terms of job arrangements, impacts of long-term RSW on MetS development should be assessed for all male employees having baseline e-ALT.

  7. Alkaline ceramidase 3 deficiency aggravates colitis and colitis-associated tumorigenesis in mice by hyperactivating the innate immune system.

    Science.gov (United States)

    Wang, K; Xu, R; Snider, A J; Schrandt, J; Li, Y; Bialkowska, A B; Li, M; Zhou, J; Hannun, Y A; Obeid, L M; Yang, V W; Mao, C

    2016-03-03

    Increasing studies suggest that ceramides differing in acyl chain length and/or degree of unsaturation have distinct roles in mediating biological responses. However, still much remains unclear about regulation and role of distinct ceramide species in the immune response. Here, we demonstrate that alkaline ceramidase 3 (Acer3) mediates the immune response by regulating the levels of C18:1-ceramide in cells of the innate immune system and that Acer3 deficiency aggravates colitis in a murine model by augmenting the expression of pro-inflammatory cytokines in myeloid and colonic epithelial cells (CECs). According to the NCBI Gene Expression Omnibus (GEO) database, ACER3 is downregulated in immune cells in response to lipopolysaccharides (LPS), a potent inducer of the innate immune response. Consistent with these data, we demonstrated that LPS downregulated both Acer3 mRNA levels and its enzymatic activity while elevating C(18:1)-ceramide, a substrate of Acer3, in murine immune cells or CECs. Knocking out Acer3 enhanced the elevation of C(18:1)-ceramide and the expression of pro-inflammatory cytokines in immune cells and CECs in response to LPS challenge. Similar to Acer3 knockout, treatment with C(18:1)-ceramide, but not C18:0-ceramide, potentiated LPS-induced expression of pro-inflammatory cytokines in immune cells. In the mouse model of dextran sulfate sodium-induced colitis, Acer3 deficiency augmented colitis-associated elevation of colonic C(18:1)-ceramide and pro-inflammatory cytokines. Acer3 deficiency aggravated diarrhea, rectal bleeding, weight loss and mortality. Pathological analyses revealed that Acer3 deficiency augmented colonic shortening, immune cell infiltration, colonic epithelial damage and systemic inflammation. Acer3 deficiency also aggravated colonic dysplasia in a mouse model of colitis-associated colorectal cancer. Taken together, these results suggest that Acer3 has an important anti-inflammatory role by suppressing cellular or tissue C(18

  8. On the origin of the liver

    Science.gov (United States)

    Friedman, Joshua R.; Kaestner, Klaus H.

    2011-01-01

    While it has been well established that the fetal liver originates from foregut endoderm, the identity of the mechanisms that maintain liver mass under both basal and injury conditions remains controversial. Dramatically different models have been proposed based on the experimental design employed. In this issue of the JCI, Malato and colleagues report their elegant new model for genetic lineage tracing of mature mouse hepatocytes using an adenoassociated virus–driven Cre recombinase. They show convincingly that maintenance of liver mass during normal turnover or in response to mild injury is achieved by mature hepatocytes, rather than cholangiocytes or specialized progenitor cells, as has been suggested by others. PMID:22105167

  9. Biomarkers for liver fibrosis

    Science.gov (United States)

    Jacobs, Jon M.; Burnum-Johnson, Kristin E.; Baker, Erin M.; Smith, Richard D.; Gritsenko, Marina A.; Orton, Daniel

    2015-09-15

    Methods and systems for diagnosing or prognosing liver fibrosis in a subject are provided. In some examples, such methods and systems can include detecting liver fibrosis-related molecules in a sample obtained from the subject, comparing expression of the molecules in the sample to controls representing expression values expected in a subject who does not have liver fibrosis or who has non-progressing fibrosis, and diagnosing or prognosing liver fibrosis in the subject when differential expression of the molecules between the sample and the controls is detected. Kits for the diagnosis or prognosis of liver fibrosis in a subject are also provided which include reagents for detecting liver fibrosis related molecules.

  10. Role of Gut Microbiota in Liver Disease.

    Science.gov (United States)

    Brenner, David A; Paik, Yong-Han; Schnabl, Bernd

    2015-01-01

    Many lines of research have established a relationship between the gut microbiome and patients with liver disease. For example, patients with cirrhosis have increased bacteremia, increased blood levels of lipopolysaccharide, and increased intestinal permeability. Patients with cirrhosis have bacterial overgrowth in the small intestine. Selective intestinal decontamination with antibiotics is beneficial for patients with decompensated cirrhosis. In experimental models of chronic liver injury with fibrosis, several toll-like receptors (TLR) are required to make mice sensitive to liver fibrosis. The presumed ligand for the TLRs are bacterial products derived from the gut microbiome, and TLR knockout mice are resistant to liver inflammation and fibrosis. We and others have characterized the association between preclinical models of liver disease in mice with the microbial diversity in their gut microbiome. In each model, including intragastric alcohol, bile duct ligation, chronic carbon tetrachloride (CCl4), administration, and genetic obesity, there is a significant change in the gut microbiome from normal control mice. However, there is not a single clear bacterial strain or pattern that distinguish mice with liver injury from controlled mice. So how can the gut microbiota affect liver disease? We can identify at least 6 changes that would result in liver injury, inflammation, and/or fibrosis. These include: (1) changes in caloric yield of diet; (2) regulation of gut permeability to release bacterial products; (3) modulation of choline metabolism; (4) production of endogenous ethanol; (5) regulation of bile acid metabolism; and (6) regulation in lipid metabolism.

  11. CKD and nonalcoholic fatty liver disease.

    Science.gov (United States)

    Targher, Giovanni; Chonchol, Michel B; Byrne, Christopher D

    2014-10-01

    The possible link between nonalcoholic fatty liver disease and chronic kidney disease (CKD) recently has attracted considerable scientific interest. Accumulating clinical evidence indicates that the presence and severity of nonalcoholic fatty liver disease is associated significantly with CKD (defined as decreased estimated glomerular filtration rate and/or proteinuria) and that nonalcoholic fatty liver disease predicts the development and progression of CKD, independently of traditional cardiorenal risk factors. Experimental evidence also suggests that nonalcoholic fatty liver disease itself may exacerbate systemic and hepatic insulin resistance, cause atherogenic dyslipidemia, and release a variety of proinflammatory, procoagulant, pro-oxidant, and profibrogenic mediators that play important roles in the development and progression of CKD. However, despite the growing evidence linking nonalcoholic fatty liver disease with CKD, it has not been definitively established whether a causal association exists. The clinical implication for these findings is that patients with nonalcoholic fatty liver disease may benefit from more intensive surveillance or early treatment interventions to decrease the risk of CKD. In this review, we discuss the evidence linking nonalcoholic fatty liver disease with CKD and the putative mechanisms by which nonalcoholic fatty liver disease contributes to kidney damage. We also briefly discuss current treatment options for this increasingly prevalent disease that is likely to have an important future impact on the global burden of disease.

  12. Liver disease in pregnancy

    Institute of Scientific and Technical Information of China (English)

    Noel M Lee; Carla W Brady

    2009-01-01

    Liver diseases in pregnancy may be categorized into liver disorders that occur only in the setting of pregnancy and liver diseases that occur coincidentally with pregnancy. Hyperemesis gravidarum, preeclampsia/eclampsia, syndrome of hemolysis, elevated liver tests and low platelets (HELLP), acute fatty liver of pregnancy, and intrahepatic cholestasis of pregnancy are pregnancy-specific disorders that may cause elevations in liver tests and hepatic dysfunction. Chronic liver diseases, including cholestatic liver disease, autoimmune hepatitis, Wilson disease, and viral hepatitis may also be seen in pregnancy. Management of liver disease in pregnancy requires collaboration between obstetricians and gastroenterologists/hepatologists. Treatment of pregnancy-specific liver disorders usually involves delivery of the fetus and supportive care, whereas management of chronic liver disease in pregnancy is directed toward optimizing control of the liver disorder. Cirrhosis in the setting of pregnancy is less commonly observed but offers unique challenges for patients and practitioners. This article reviews the epidemiology, pathophysiology, diagnosis, and management of liver diseases seen in pregnancy.

  13. Bioartificial liver: current status.

    Science.gov (United States)

    Pless, G; Sauer, I M

    2005-11-01

    Liver failure remains a life-threatening syndrome. With the growing disparity between the number of suitable donor organs and the number of patients awaiting transplantation, efforts have been made to optimize the allocation of organs, to find alternatives to cadaveric liver transplantation, and to develop extracorporeal methods to support or replace the function of the failing organ. An extracorporeal liver support system has to provide the main functions of the liver: detoxification, synthesis, and regulation. The understanding that the critical issue of the clinical syndrome in liver failure is the accumulation of toxins not cleared by the failing liver led to the development of artificial filtration and adsorption devices (artificial liver support). Based on this hypothesis, the removal of lipophilic, albumin-bound substances, such as bilirubin, bile acids, metabolites of aromatic amino acids, medium-chain fatty acids, and cytokines, should be beneficial to the clinical course of a patient in liver failure. Artificial detoxification devices currently under clinical evaluation include the Molecular Adsorbent Recirculating System (MARS), Single-Pass Albumin Dialysis (SPAD), and the Prometheus system. The complex tasks of regulation and synthesis remain to be addressed by the use of liver cells (bioartificial liver support). The Extracorporeal Liver Assist Device (ELAD), HepatAssist, Modular Extracorporeal Liver Support system (MELS), and the Amsterdam Medical Center Bioartificial Liver (AMC-BAL) are bioartificial systems. This article gives a brief overview on these artificial and bioartificial devices and discusses remaining obstacles.

  14. Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Kamran Qureshi; Gary A Abrams

    2007-01-01

    Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause of liver-related morbidity and mortality.It can develop secondary to numerous causes but a great majority of NAFLD cases occur in patients who are obese or present with other components of metabolic syndrome (hypertension, dyslipidemia, diabetes). This is called primary NAFLD and insulin resistance plays a key role in its pathogenesis. Obesity is characterized by expanded adipose tissue, which is under a state of chronic inflammation. This disturbs the normal storage and endocrine functions of adipose tissue. In obesity, the secretome (adipokines, cytokines, free fatty acids and other lipid moieties) of fatty tissue is amplified, which through its autocrine, paracrine actions in fat tissue and systemic effects especially in the liver leads to an altered metabolic state with insulin resistance (IR). IR leads to hyperglycemia and reactive hyperinsulinemia, which stimulates lipid-accumulating processes and impairs hepatic lipid metabolism. IR enhances free fatty acid delivery to liver from the adipose tissue storage due to uninhibited lipolysis. These changes result in hepatic abnormal fat accumulation, which may initiate the hepatic IR and further aggravate the altered metabolic state of whole body. Hepatic steatosis can also be explained by the fact that there is enhanced dietary fat delivery and physical inactivity. IR and NAFLD are also seen in various lipodystrophic states in contrary to popular belief that these problems only occur due to excessive adiposity in obesity. Hence, altered physiology of adipose tissue is central to development of IR,metabolic syndrome and NAFLD.

  15. Pseudomonas aeruginosa biofilm aggravates skin inflammatory response in BALB/c mice in a novel chronic wound model

    DEFF Research Database (Denmark)

    Trøstrup, Hannah; Thomsen, Kim; Christophersen, Lars J

    2013-01-01

    bacteria organized in clusters, resembling biofilms, and inflammation located adjacent to the PA. The chronic wound infection showed a higher number of PAO1 in the BALB/c mice at day 4 after infection as compared to C3H/HeN mice (p ... in the chronic wounds of BALB/c mice was observed at day 7 (p biofilm infection in mice. The results showed an aggravating impact of local inflammation induced by PA biofilms......Chronic wounds are presumed to persist in the inflammatory state, preventing healing. Emerging evidence indicates a clinical impact of bacterial biofilms in soft tissues, including Pseudomonas aeruginosa (PA) biofilms. To further investigate this, we developed a chronic PA biofilm wound infection...

  16. [Case of distal renal tubular acidosis complicated with renal diabetes insipidus, showing aggravation of symptoms with occurrence of diabetes mellitus].

    Science.gov (United States)

    Liu, Hexing; Tomoda, Fumihiro; Koike, Tsutomu; Ohara, Maiko; Nakagawa, Taizo; Kagitani, Satoshi; Inoue, Hiroshi

    2011-01-01

    We report herein a 27-year-old male case of inherited distal renal tubular acidosis complicated with renal diabetes insipidus, the symptoms of which were aggravated by the occurrence of diabetes mellitus. At 2 months after birth, he was diagnosed as having inherited distal renal tubular acidosis and thereafter supplementation of both potassium and alkali was started to treat his hypokalemia and metabolic acidosis. At the age of 4 years, calcification of the bilateral renal medulla was detected by computed tomography. Subsequently his urinary volume gradually increased and polyuria of approximately 4 L/day persisted. At the age of 27 years, he became fond of sugar-sweetened drinks and also often forgot to take the medicine. He was admitted to our hospital due to polyuria of more than 10 L day, muscle weakness and gait disturbance. Laboratory tests disclosed worsening of both hypokalemia and metabolic acidosis in addition to severe hyperglycemia. It seemed likely that occurrence of diabetes mellitus and cessation of medications can induce osmotic diuresis and aggravate hypokalemia and metabolic acidosis. Consequently, severe dehydration, hypokalemia-induced damage of his urinary concentration ability and enhancement of the renin angiotensin system occurred and thereby possibly worsened his hypokalemia and metabolic acidosis. As normalization of hyperglycemia and metabolic acidosis might have exacerbated hypokalemia further, dehydration and hypokalemia were treated first. Following intensive treatment, these abnormalities were improved, but polyuria persisted. Elevated plasma antidiuretic hormone (12.0 pg/mL) and deficit of renal responses to antidiuretic hormone suggested that the polyuria was attributable to the preexisting renal diabetes insipidus possibly caused by bilateral renal medulla calcification. Thiazide diuretic or nonsteroidal anti-inflammatory drugs were not effective for the treatment of diabetes insipidus in the present case.

  17. Tests for Liver Cancer

    Science.gov (United States)

    ... has come back after treatment Alpha-fetoprotein blood (AFP) test AFP is normally present at high levels in the ... liver disease, liver cancer, or other cancers. If AFP levels are very high in someone with a ...

  18. Autoimmune liver disease panel

    Science.gov (United States)

    Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cirrhosis. This group of tests helps your health care provider ...

  19. Alcoholic liver disease

    Science.gov (United States)

    Liver disease due to alcohol; Cirrhosis or hepatitis - alcoholic; Laennec's cirrhosis ... Alcoholic liver disease occurs after years of heavy drinking. Over time, scarring and cirrhosis can occur. Cirrhosis is the ...

  20. Antioxidants in liver health

    Institute of Scientific and Technical Information of China (English)

    Sael; Casas-Grajales; Pablo; Muriel

    2015-01-01

    Liver diseases are a worldwide medical problem because the liver is the principal detoxifying organ and maintains metabolic homeostasis. The liver metabolizes various compounds that produce free radicals(FR).However, antioxidants scavenge FR and maintain the oxidative/antioxidative balance in the liver. When the liver oxidative/antioxidative balance is disrupted, the state is termed oxidative stress. Oxidative stress leadsto deleterious processes in the liver and produces liver diseases. Therefore, restoring antioxidants is essential to maintain homeostasis. One method of restoring antioxidants is to consume natural compounds with antioxidant capacity. The objective of this review is to provide information pertaining to various antioxidants found in food that have demonstrated utility in improving liver diseases.

  1. Alcohol-Related Liver Disease

    Science.gov (United States)

    ... Baby Boomers Get Tested Core Programs HE Webinar Disney 2014 5 Ways to Love Your Liver Liver ... Drive Away Liver Disease Liver Lowdown Aug 2013 Disney Marathon In The Field Healthy Foods Diet Recommendations ...

  2. Percutaneous liver biopsy.

    Science.gov (United States)

    Rustagi, Tarun; Newton, Eric; Kar, Premashish

    2010-01-01

    Percutaneous liver biopsy has been performed for more than 120 years, and remains an important diagnostic procedure for the management of hepatobiliary disorders. Modern biochemical, immunologic, and radiographic techniques have facilitated the diagnosis and management of liver diseases but have not made liver biopsy obsolete. This comprehensive review article will discuss the history of development of percutaneous liver biopsy, its indications, contraindications, complications and the various aspects of the biopsy procedure in detail.

  3. Alcohol and liver

    Institute of Scientific and Technical Information of China (English)

    Natalia Osna

    2009-01-01

    @@ Liver is a primary site of ethanol metabolism, which makes this organ susceptible to alcohol-induced damage.Alcoholic liver disease (ALD) has many manifestations and complicated pathogenesis. In this Topic Highlight, we included the key reviews that characterize new findings about the mechanisms of ALD development and might be of strong interest for clinicians and researchers involved in liver alcohol studies.

  4. Research Areas: Liver Disease

    Science.gov (United States)

    ... and C, or by genetic mutations. Other liver diseases can be triggered by autoimmune reactions or drug toxicity. The rise in obesity in the United States has led to a rise in nonalcoholic fatty liver disease. Many liver diseases place individuals at higher risk ...

  5. LIVER AND BILIARY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    11.1 Liver cirrhosis and fatty liver2003230 The relevance of fatty liver and insulin resistance. LIU Jun(刘军), et al. Dept Endocrinol, Zhong-shan Hosp, Fudan Univ, Shanghai 200032, Shanghai Med J 2003; 16(1): 14-17

  6. LIVER AND BILIARY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    9.1 Liver Function2007108 Blood pressure changes post liver transplantation in 206 recipients. LIU Hai(刘海),et al. 1st People′s Hosp, Shanghai Jiaotong Univ, Shanghai 200080. Chin J Cardiol 2006;34(10):902-904. Objective To study the blood pressure (BP)changes in the liver transplant recipients.

  7. Hepatic (Liver) Function Panel

    Science.gov (United States)

    ... 1- to 2-Year-Old Blood Test: Hepatic (Liver) Function Panel KidsHealth > For Parents > Blood Test: Hepatic (Liver) Function Panel Print A A A What's in ... Is The hepatic function panel, also known as liver function tests, is a group of seven tests ...

  8. LIVER AND BILIARY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    9.1 Liver cirrhosis and fatty liver2003335 The effects of weight reduction in reversing fatty liver changes in overweight and obese patients.ZHU Huijuan(朱惠娟), et al.Dept Endocrinol, PUMC Hosp,CAMS & PUMC, Beijing 100730. Chin J Intern Med 2003:42(2):98-102.Objective:To study the effects of weight loss on non-

  9. Imaging in liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Settimo Caruso; Roberto Miraglia; Luigi Maruzzelli; Salvatore Gruttadauria; Angelo Luca; Bruno Gridelli

    2009-01-01

    The aim of this study was to illustrate the role of noninvasive imaging tools such as ultrasonography, multidetector row computed tomography, and magnetic resonance imaging in the evaluation of pediatric and adult liver recipients and potential liver donors, and in the detection of potential complications arising from liver transplantation.

  10. Experimental study on treatment of liver fibrosis by hepatic oval cell transplantation via spleen injection%肝卵圆细胞经脾脏移植治疗肝纤维化的实验研究

    Institute of Scientific and Technical Information of China (English)

    刘波; 林楠; 胡鲲鹏

    2009-01-01

    especially in the group of ceasing CCl4 injection. Conclusion After transplanted into the liver by spleen injection, hepatic oval cells could plant in the portal area, which improve liver function and alleviate the cirrhosis level.%有所减轻,尤以停止注射四氯化碳组明显.结论 携带GFP的基因卵圆细胞经脾注射至肝纤维化小鼠体内后,可定植于受者肝脏内,并可缓解肝硬化的进展,促进肝纤维的逆转.

  11. Current Concepts in Diabetes Mellitus and Chronic Liver Disease: Clinical Outcomes, Hepatitis C Virus Association, and Therapy.

    Science.gov (United States)

    García-Compeán, Diego; González-González, José Alberto; Lavalle-González, Fernando Javier; González-Moreno, Emmanuel Irineo; Villarreal-Pérez, Jesús Zacarías; Maldonado-Garza, Héctor J

    2016-02-01

    Hereditary type 2 diabetes mellitus is a risk factor for chronic liver disease, and ~30 % of patients with liver cirrhosis develop diabetes. Diabetes mellitus has been associated with cirrhotic and non-cirrhotic hepatitis C virus liver infection, can aggravate the course the liver infection, and can induce a lower sustained response to antiviral treatment. Evidences that HCV may induce metabolic and autoimmune disturbances leading to hypobetalipoproteinemia, steatosis, insulin resistance, impaired glucose tolerance, thyroid disease, and gonadal dysfunction have been found. Prospective studies have demonstrated that diabetes increases the risk of liver complications and death in patients with cirrhosis. However, treatment of diabetes in these patients is complex, as antidiabetic drugs can promote hypoglycemia and lactic acidosis. There have been few therapeutic studies evaluating antidiabetic treatments in patients with liver cirrhosis published to date; thus, the optimal treatment for diabetes and the impact of treatment on morbidity and mortality are not clearly known. As numbers of patients with chronic liver disease and diabetes mellitus are increasing, largely because of the global epidemics of obesity and nonalcoholic fatty liver disease, evaluation of treatment options is becoming more important. This review discusses new concepts on hepatogenous diabetes, the diabetes mellitus–hepatitis C virus association, and clinical implications of diabetes mellitus in patients with chronic liver disease. In addition, the effectiveness and safety of old and new antidiabetic drugs, including incretin-based therapies, will be described.

  12. PPAR and Liver Injury in HIV-Infected Patients

    Directory of Open Access Journals (Sweden)

    Maud Lemoine

    2009-01-01

    Full Text Available Due to the introduction of active HIV antiretroviral treatment, AIDS-related morbidity and mortality have markedly decreased and liver diseases are now a major cause of morbidity and mortality in HIV-infected patients. Chronic liver injury encompasses a wide spectrum of diseases due to HCV and HBV coinfection, drug-related toxicity, and NASH. HIV-infected patients who are receiving treatment present with a high prevalence of metabolic complications and lipodystrophy. Those patients are at high risk of nonalcoholic fatty liver disease, the liver feature of the metabolic syndrome. This review will focus on (1 the liver injuries in HIV-infected patients; (2 both the current experimental and human data regarding PPAR and liver diseases; (3 the interactions between HIV and PPAR; (4 the potential use of PPAR agonists for the management of HIV-related liver diseases.

  13. TNF-Like Weak Inducer of Apoptosis Aggravates Left Ventricular Dysfunction after Myocardial Infarction in Mice

    Directory of Open Access Journals (Sweden)

    Kai-Uwe Jarr

    2014-01-01

    Full Text Available Background. TNF-like weak inducer of apoptosis (TWEAK has recently been shown to be potentially involved in adverse cardiac remodeling. However, neither the exact role of TWEAK itself nor of its receptor Fn14 in this setting is known. Aim of the Study. To analyze the effects of sTWEAK on myocardial function and gene expression in response to experimental myocardial infarction in mice. Results. TWEAK directly suppressed the expression of PGC-1α and genes of oxidative phosphorylation (OXPHOS in cardiomyocytes. Systemic sTWEAK application after MI resulted in reduced left ventricular function and increased mortality without changes in interstitial fibrosis or infarct size. Molecular analysis revealed decreased phosphorylation of PI3K/Akt and ERK1/2 pathways associated with reduced expression of PGC-1α and PPARα. Likewise, expression of OXPHOS genes such as atp5O, cycs, cox5b, and ndufb5 was also reduced. Fn14 -/- mice showed significantly improved left ventricular function and PGC-1α levels after MI compared to their respective WT littermates (Fn14 +/+. Finally, inhibition of intrinsic TWEAK with anti-TWEAK antibodies resulted in improved left ventricular function and survival. Conclusions. TWEAK exerted maladaptive effects in mice after myocardial infarction most likely via direct effects on cardiomyocytes. Analysis of the potential mechanisms revealed that TWEAK reduced metabolic adaptations to increased cardiac workload by inhibition of PGC-1α.

  14. High-NaCl Diet Aggravates Cardiac Injury in Rats with Adenine-Induced Chronic Renal Failure and Increases Serum Troponin T Levels

    DEFF Research Database (Denmark)

    Kashioulis, Pavlos; Hammarsten, Ola; Marcussen, Niels

    2016-01-01

    correlation between the degree of LV fibrosis and serum cTnT levels in ACRF rats (r = 0.81, p produces LV injury and aggravates increases in serum cTnT levels, presumably by causing hypertension-induced small artery lesions leading...

  15. Animal experimental studies on the influence of fatty infiltration of the liver on tissue relaxation times and signal changes in MRT; Tierexperimentelle Studie ueber den Einfluss von Leberzellverfettungen auf die Gewebsrelaxationszeiten und Signalveraenderungen in der Magnetresonanztomographie

    Energy Technology Data Exchange (ETDEWEB)

    Kreft, B. [Radiologische Klinik der Univ. Bonn (Germany); Stark, D. [Dept. of Radiology, Univ. of Massachusetts Medical Center, Worcester (United States); Schild, H. [Radiologische Klinik der Univ. Bonn (Germany)

    1995-02-01

    Using a spectrometer (n=60) in vitro and MRT imaging (n=8) in vivo, we studied the influence of fatty changes of liver cells on the relaxation times of the liver (two animal models of fatty liver disease/orotic acid, L-ethionine). Induction of fatty degeneration of the liver by means of an orotic acid diet resulted in pure deposition of fat in the liver without any histological or serological proof of inflammatory changes. Although accumulation of triglyceride in the liver reduced the T{sub 1} relaxation time only relatively slightly (-15%), there was good correlation (r=0.88) between fat content and T{sub 1}. There was also good correlation (r=0.92) between T{sub 2} and histological fat content. Inflammatory changes besides fatty deposition were seen both serologically and histologically in the L-ethionine model, so that the fatty content did not correlate with T{sub 1}. In-vivo MRT imaging showed that spin-echo sequences are inappropriate for diagnosing fatty infiltration of the liver despite the relaxation time changes produced by the fatty deposition. On the other hand, chemical-shift imaging sequences are very sensitive to identify fatty deposits, and are also independent of any additionally existing inflammatory changes. (orig.) [Deutsch] Anhand von zwei tierexperimentellen Fettlebermodellen (Orotsaeurediaet, L-Ethionin) wurde der Einfluss einer Leberzellverfettung auf die Relaxationszeiten der Leber in vitro mittels Spektrometer (n=60) und in vivo durch MRT-Bildgebung (n=8) untersucht. Die Fettleberinduktion durch Orotsaeurediaet fuehrte zu einer reinen Fetteinlagerung in der Leber ohne histologischen und serologischen Nachweis von entzuendlichen Veraenderungen. Obwohl die Tryglyceridanreicherung in der Leber nur zu einer relativ geringen Verkuerzung der T{sub 1}-Relaxationszeit (-15%) der Leber fuehrte, fand sich eine gute Korrelation (r=0,88) zwischen dem Fettgehalt und T{sub 1}. Die T{sub 2}-Relaxationszeit zeigte ebenfalls eine gute Korrelation (r=0

  16. Importance Rat Liver Morphology and Vasculature in Surgical Research.

    Science.gov (United States)

    Vdoviaková, Katarína; Vdoviaková, Katarína; Petrovová, Eva; Krešáková, Lenka; Maloveská, Marcela; Teleky, Jana; Jenčová, Janka; Živčák, Jozef; Jenča, Andrej

    2016-12-02

    BACKGROUND The laboratory rat is one of the most popular experimental models for the experimental surgery of the liver. The objective of this study was to investigate the morphometric parameters, physiological data, differences in configuration of liver lobes, biliary system, and vasculature (arteries, veins, and lymphatic vessels) of the liver in laboratory rats. In addition, this study supports the anatomic literature and identified similarities and differences with human and other mammals. MATERIAL AND METHODS Forty laboratory rats were dissected to prepare corrosion casts of vascular system specimens (n=20), determine the lymph vessels and lymph nodes (n=10), and for macroscopic anatomical dissection (n=10) of the rat liver. The results are listed in percentages. The anatomical nomenclature of the liver morphology, its arteries, veins, lymph nodes, and lymphatic vessels are in accordance with Nomina Anatomica Veterinaria. RESULTS We found many variations in origin, direction, and division of the arterial, venous, and lymphatic systems in rat livers, and found differences in morphometric parameters compared to results reported by other authors. The portal vein was formed by 4 tributaries in 23%, by 3 branches in 64%, and by 2 tributaries in 13%. The liver lymph was drained to the 2 different lymph nodes. The nomenclature and morphological characteristics of the rat liver vary among authors. CONCLUSIONS Our results may be useful for the planing of experimental surgery and for cooperation with other investigation methods to help fight liver diseases in human populations.

  17. Hypoxia,angiogenesis and liver fibrogenesis in the progression of chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Claudia; Paternostro; Ezio; David; Erica; Novo; Maurizio; Parola

    2010-01-01

    Angiogenesis is a dynamic,hypoxia-stimulated and growth factor-dependent process,and is currently referred to as the formation of new vessels from preexisting blood vessels.Experimental and clinical studies have unequivocally reported that hepatic angiogenesis,irrespective of aetiology,occurs in conditions of chronic liver diseases(CLDs) characterized by perpetuation of cell injury and death,inflammatory response and progressive fibrogenesis.Angiogenesis and related changes in liver vascular architecture,th...

  18. Compound formula Jiukele's efficacy and its mechanisms in prevention and treatment of experimental alcoholic liver fibrosis in rats%酒客乐对大鼠酒精性肝纤维化疗效及机制的研究

    Institute of Scientific and Technical Information of China (English)

    甘爱萍; 李云桥; 陈宏慈

    2011-01-01

    目的:探讨中药复方酒客乐对大鼠酒精性肝纤维化的防治作用及其机制.方法:采用白酒-吡唑-橄榄油的混悬液灌胃建立酒精性肝纤维化大鼠模型.雄性Wistar大鼠随机分为正常对照组、造模组、治疗组及酒客乐高、低剂量预防组.实验第12周后,除治疗组外,采集标本;治疗组于实验第16周后采集标本,观察酒客乐对大鼠体重、肝功能、血清PⅢP、LN含量以及肝脏病理形态改变、肝脏表达TGF-β1水平的影响.结果:造模组大鼠体重、血清ALT、AST、PⅢP、LN、肝脏表达TGF-β1水平、肝脏病理形态改变与正常对照组比较差异有显著性意义(P<0.01).酒客乐高剂量预防组大鼠体重增长与正常对照组差异无显著性意义(P>0.05).酒客乐高、低剂量预防组、治疗组大鼠血清ALT、AST、PⅢP、LN含量明显低于造模组(P<0.01).酒客乐能减轻大鼠肝脏病理形态改变,抑制其肝脏TGF-β1产生,酒客乐高、低剂量预防组、治疗组大鼠TGF-β1水平含量明显低于造模组,差异有显著性意义(P<0.01).结论:酒客乐具有防治大鼠酒精性肝纤维化的作用,其作用机制可能为:①直接作用:抑制肝脏细胞外基质的沉积,减轻肝脏病理形态改变;②间接作用:保护肝功能,增强免疫功能,纠正肝脏代谢紊乱.%Objective: To investigate the efficacy of Chinese compound formula Jiukele in the prevention and treatment of ethanol - induced liver fibrosis in the rats and its mechanisms. Methods: Forty male Wistar rats were divided randomly into 5 groups: normal control group, model group, therapy group, high and low dose prophylactic group. The mixture of alcohol (55° ) , pyrazole and olive oils was fed to the stomach of the rats of model group every morning {!'■ 00 - 8: 00) . The rat model was successfully established in 12 weeks. The Jiukele was given to the rats of therapy group for another 4 weeks after rat model was established

  19. Clinical Study on Treatment of Liver Fibrosis of Chronic Hepatitis B Patients with Ginkgo Leaf

    Institute of Scientific and Technical Information of China (English)

    何云; 袁凤仪; 王建宾; 邵淑莲; 袁红波; 黄晓欣

    2002-01-01

    Objective: To study the anti-liver fibrosis effect of Ginkgo leaf in patients with chronic hepatitis B.Methods: Eighty-six patients with chronic hepatitis B were randomly divided into two groups with similar general condition. The 42 patients in the treated group were treated with Ginkgo leaf tablet (GLT), and the 44 patients in the control group were treated with Yiganling tablet (益肝灵片). The treatment was conducted for 3 successive months in both groups. Changes in the histo-pathology of liver, serum levels of platelet activating factor (PAF), hyaluronic acid (HA), collagen type Ⅳ (C-Ⅳ), laminin (LN) and pro-collagen peptide type Ⅲ (PCⅢ)were observed before and after treatment. Results: The markedly effective rate and the total effective rate in the treated group were 45.1% and 76.2% respectively, while in the control group the corresponding rates were 18.2% and 43.2%. Comparison between the two groups showed significant difference (P<0.01). Serum levels of PAF, HA, C-Ⅳ, LN and PCⅢ were lowered significantly in the treated group after treatment. Compared with the corresponding parameters in the control group after treatment, the differences were all significant (P<0.01 or P<0.05). The pathological examination of liver showed improvement in both groups, the inflammation grade lowered in 10 patients (55.6%) of the treated group and in 5 patients (35.7%) of the control group, insignificant difference was shown between them. But in comparing the fibrosis staging lowering patients between the two groups, 12 patients (66.7%) vs 3 patients (21.4%), the difference was significant (P<0.05). Moreover, there were 4 patients in the control group with their fibrosis aggravated, while in the treated group, none was aggravated (P<0.05).Conclusion: Ginkgo leaf tablet has some liver protective and anti-liver fibrosis benefits.

  20. IL-33 Aggravates DSS-Induced Acute Colitis in Mouse Colon Lamina Propria by Enhancing Th2 Cell Responses.

    Science.gov (United States)

    Zhu, Junfeng; Yang, Fangli; Sang, Lixuan; Zhai, Jingbo; Zhang, Xiaoqing; Yue, Dan; Li, Shengjun; Li, Yan; Lu, Changlong; Sun, Xun

    2015-01-01

    Interleukin- (IL-) 33, a member of the IL-1 cytokine family, is an important modulator of the immune system associated with several immune-mediated diseases. IL-33 was expressed in high level on epithelial cells of intestinal tract. It suggested that IL-33 plays a potential role in inflammatory bowel diseases (IBD). We investigated the role of interleukin- (IL-) 33 in dextran sulphate sodium- (DSS-) induced acute colitis in mice using recombinant mouse IL-33 protein (rIL-33). We found that DSS-induced acute colitis was aggravated by rIL-33 treatment. rIL-33-treated DSS mice showed markedly reduced levels of interferon- (IFN-)γ and IL-17A in their colon lamina propria lymphocytes (LPL), but the levels of Th2 cytokines, such as IL-5 and IL-13, in these cells were significantly increased, compared to DSS mice treated with PBS. Our results suggested that IL-33 stimulated CD4(+)T cells and caused the cell to adopt a Th2-type response but at the same time suppressed Th17 and Th1 cell responses. Therefore, IL-33 may be involved in pathogenesis of DSS-induced acute colitis by promoting Th2 cell response in intestinal mucosa of mice. Modulation of IL-33/ST2 signaling by monoclonal antibody (mAb) could be a novel biological therapy in DSS-induced acute colitis.

  1. Accelerated dysbiosis of gut microbiota during aggravation of DSS-induced colitis by a butyrate-producing bacterium.

    Science.gov (United States)

    Zhang, Qianpeng; Wu, Yanqiu; Wang, Jing; Wu, Guojun; Long, Wenmin; Xue, Zhengsheng; Wang, Linghua; Zhang, Xiaojun; Pang, Xiaoyan; Zhao, Yufeng; Zhao, Liping; Zhang, Chenhong

    2016-06-06

    Butyrate-producing bacteria (BPB) are potential probiotic candidates for inflammatory bowel diseases as they are often depleted in the diseased gut microbiota. However, here we found that augmentation of a human-derived butyrate-producing strain, Anaerostipes hadrus BPB5, significantly aggravated colitis in dextran sulphate sodium (DSS)-treated mice while exerted no detrimental effect in healthy mice. We explored how the interaction between BPB5 and gut microbiota may contribute to this differential impact on the hosts. Butyrate production and severity of colitis were assessed in both healthy and DSS-treated mice, and gut microbiota structural changes were analysed using high-throughput sequencing. BPB5-inoculated healthy mice showed no signs of colitis, but increased butyrate content in the gut. In DSS-treated mice, BPB5 augmentation did not increase butyrate content, but induced significantly more severe disease activity index and much higher mortality. BPB5 didn't induce significant changes of gut microbiota in healthy hosts, but expedited the structural shifts 3 days earlier toward the disease phase in BPB5-augmented than DSS-treated animals. The differential response of gut microbiota in healthy and DSS-treated mice to the same potentially beneficial bacterium with drastically different health consequences suggest that animals with dysbiotic gut microbiota should also be employed for the safety assessment of probiotic candidates.

  2. Absence of Intestinal PPARγ Aggravates Acute Infectious Colitis in Mice through a Lipocalin-2–Dependent Pathway

    Science.gov (United States)

    Kundu, Parag; Ling, Teo Wei; Korecka, Agata; Li, Yinghui; D'Arienzo, Rossana; Bunte, Ralph M.; Berger, Thorsten; Arulampalam, Velmurugesan; Chambon, Pierre; Mak, Tak Wah; Wahli, Walter; Pettersson, Sven

    2014-01-01

    To be able to colonize its host, invading Salmonella enterica serovar Typhimurium must disrupt and severely affect host-microbiome homeostasis. Here we report that S. Typhimurium induces acute infectious colitis by inhibiting peroxisome proliferator-activated receptor gamma (PPARγ) expression in intestinal epithelial cells. Interestingly, this PPARγ down-regulation by S. Typhimurium is independent of TLR-4 signaling but triggers a marked elevation of host innate immune response genes, including that encoding the antimicrobial peptide lipocalin-2 (Lcn2). Accumulation of Lcn2 stabilizes the metalloproteinase MMP-9 via extracellular binding, which further aggravates the colitis. Remarkably, when exposed to S. Typhimurium, Lcn2-null mice exhibited a drastic reduction of the colitis and remained protected even at later stages of infection. Our data suggest a mechanism in which S. Typhimurium hijacks the control of host immune response genes such as those encoding PPARγ and Lcn2 to acquire residence in a host, which by evolution has established a symbiotic relation with its microbiome community to prevent pathogen invasion. PMID:24465207

  3. Partial pyruvate kinase deficiency aggravates the phenotypic expression of band 3 deficiency in a family with hereditary spherocytosis.

    Science.gov (United States)

    van Zwieten, Rob; van Oirschot, Brigitte A; Veldthuis, Martijn; Dobbe, Johannes G; Streekstra, Geert J; van Solinge, Wouter W; Schutgens, Roger E G; van Wijk, Richard

    2015-03-01

    In a family with mild dominant spherocytosis, affected members showed partial band 3 deficiency. The index patient showed more severe clinical symptoms than his relatives, and his red blood cells displayed concomitant low pyruvate kinase activity. We investigated the contribution of partial PK deficiency to the phenotypic expression of mutant band 3 in this family. Pyruvate kinase deficiency and band 3 deficiency were characterized by DNA analysis. Results of red cell osmotic fragility testing, the results of cell deformability obtained by the Automated Rheoscope and Cell Analyzer and the results obtained by Osmotic Gradient Ektacytometry, which is a combination of these tests, were related to the red cell ATP content. Spherocytosis in this family was due to a novel heterozygous mutation in SLC4A1, the gene for band 3. Reduced PK activity of the index patient was attributed to a novel mutation in PKLR inherited from his mother, who was without clinical symptoms. Partial PK deficiency was associated with decreased red cell ATP content and markedly increased osmotic fragility. This suggests an aggravating effect of low ATP levels on the phenotypic expression of band 3 deficiency.

  4. A new update for radiocontrast-induced nephropathy aggravated with glycerol in rats: the protective potential of epigallocatechin-3-gallate.

    Science.gov (United States)

    Palabiyik, Saziye Sezin; Dincer, Busra; Cadirci, Elif; Cinar, Irfan; Gundogdu, Cemal; Polat, Beyzagul; Yayla, Muhammed; Halici, Zekai

    2017-11-01

    Contrast media (CM) is known to have nephrotoxic adverse effects. Epigallocatechin-3-gallate (EGCG) is the most abundant and active catechin in green tea, and has strong antioxidant and anti-inflammatory properties. This study investigated whether EGCG can reduce contrast-induced nephrotoxicity (CIN), alone or with glycerol (GLY)-induced renal damage, and to understand its mechanisms of protection against toxicity, using models of GLY and CIN in rats. The rats were separated into eight groups (n = 6 in each), as follows: Healthy, GLY, CM, GLY + CM, CM + EGCG 50 mg/kg (po), GLY + CM + EGCG 50 mg/kg (po), CM + EGCG 100 mg/kg (po), and GLY + CM + EGCG 100 mg/kg (po). Both doses of EGCG protected against CM-induced renal dysfunction, as measured by serum creatinine and blood urea nitrogen (BUN). In addition, EGCG treatment markedly improved CIN-induced oxidative stress, and resulted in a significant down-regulatory effect on tumor necrosis factor (TNF)-α and nuclear factor (NF)-κB mRNA expression. Moreover, histopathological analysis showed that EGCG also attenuated CM-induced kidney damage. Considering the potential clinical use of CM and the numerous health benefits of EGCG, this study showed the protective role of multi-dose EGCG treatment on CIN and GLY-aggravated CIN through different mechanisms.

  5. Aggravation of brain infarction through an increase in acrolein production and a decrease in glutathione with aging.

    Science.gov (United States)

    Uemura, Takeshi; Watanabe, Kenta; Ishibashi, Misaki; Saiki, Ryotaro; Kuni, Kyoshiro; Nishimura, Kazuhiro; Toida, Toshihiko; Kashiwagi, Keiko; Igarashi, Kazuei

    2016-04-29

    We previously reported that tissue damage during brain infarction was mainly caused by inactivation of proteins by acrolein. This time, it was tested why brain infarction increases in parallel with aging. A mouse model of photochemically induced thrombosis (PIT) was studied using 2, 6, and 12 month-old female C57BL/6 mice. The size of brain infarction in the mouse PIT model increased with aging. The volume of brain infarction in 12 month-old mice was approximately 2-fold larger than that in 2 month-old mice. The larger brain infarction in 12 month-old mice was due to an increase in acrolein based on an increase in the activity of spermine oxidase, together with a decrease in glutathione (GSH), a major acrolein-detoxifying compound in cells, based on the decrease in one of the subunits of glutathione biosynthesizing enzymes, γ-glutamylcysteine ligase modifier subunit, with aging. The results indicate that aggravation of brain infarction with aging was mainly due to the increase in acrolein production and the decrease in GSH in brain.

  6. Continuing Exposure to Low-Dose Nonylphenol Aggravates Adenine-Induced Chronic Renal Dysfunction and Role of Rosuvastatin Therapy

    Directory of Open Access Journals (Sweden)

    Yen Chia-Hung

    2012-07-01

    Full Text Available Abstract Background Nonylphenol (NP, an environmental organic compound, has been demonstrated to enhance reactive-oxygen species (ROS synthesis. Chronic exposure to low-dose adenine (AD has been reported to induce chronic kidney disease (CKD. Methods In this study, we tested the hypothesis that chronic exposure to NP will aggravate AD-induced CKD through increasing generations of inflammation, ROS, and apoptosis that could be attenuated by rosuvastatin. Fifty male Wistar rats were equally divided into group 1 (control, group 2 (AD in fodder at a concentration of 0.25%, group 3 (NP: 2 mg/kg/day, group 4 (combined AD & NP, and group 5 (AD-NP + rosuvastatin: 20 mg/kg/day. Treatment was continued for 24 weeks for all animals before being sacrificed. Results By the end of 24 weeks, serum blood urea nitrogen (BUN and creatinine levels were increased in group 4 than in groups 1–3, but significantly reduced in group 5 as compared with group 4 (all p  Conclusion NP worsened AD-induced CKD that could be reversed by rosuvastatin therapy.

  7. Food-advanced glycation end products aggravate the diabetic vascular complications via modulating the AGEs/RAGE pathway.

    Science.gov (United States)

    Lv, Xing; Lv, Gao-Hong; Dai, Guo-Ying; Sun, Hong-Mei; Xu, Hui-Qin

    2016-11-01

    The aim of this study was to investigate the effects of high-advanced glycation end products (AGEs) diet on diabetic vascular complications. The Streptozocin (STZ)-induced diabetic mice were fed with high-AGEs diet. Diabetic characteristics, indicators of renal and cardiovascular functions, and pathohistology of pancreas, heart and renal were evaluated. AGEs/RAGE/ROS pathway parameters were determined. During the experiments, the diabetic mice exhibited typical characteristics including weight loss, polydipsia, polyphagia, polyuria, high-blood glucose, and low-serum insulin levels. However, high-AGEs diet effectively aggravated these diabetic characteristics. It also increased the 24-h urine protein levels, serum levels of urea nitrogen, creatinine, c-reactive protein (CRP), low density lipoprotein (LDL), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the diabetic mice. High-AGEs diet deteriorated the histology of pancreas, heart, and kidneys, and caused structural alterations of endothelial cells, mesangial cells and podocytes in renal cortex. Eventually, high-AGEs diet contributed to the high-AGE levels in serum and kidneys, high-levels of reactive oxygen species (ROS) and low-levels of superoxide dismutase (SOD) in serum, heart, and kidneys. It also upregulated RAGE mRNA and protein expression in heart and kidneys. Our results showed that high-AGEs diet deteriorated vascular complications in the diabetic mice. The activation of AGEs/RAGE/ROS pathway may be involved in the pathogenesis of vascular complications in diabetes.

  8. [Liver and sport].

    Science.gov (United States)

    Watelet, J

    2008-11-01

    The liver is a vital organ and plays a central role in energy exchange, protein synthesis as well as the elimination of waste products from the body. Acute and chronic injury may disturb a variety of liver functions to different degrees. Over the last three decades, the effects of physical activity and competitive sport on the liver have been described by various investigators. These include viral hepatitis and drug-induced liver disorders. Herein, we review acute and chronic liver diseases potentially caused by sport. Team physicians, trainers and others, responsible for the health of athletes, should be familiar with the risk factors, clinical features, and consequences of liver diseases that occur in sports.

  9. Fatty liver in children

    OpenAIRE

    Rafeey, Mandana; Mortazavi, Fakhrossadat; Mogaddasi, Nafiseh; Robabeh, Ghergherehchi; Ghaffari, Shamsi; Hasani, Alka

    2009-01-01

    Aims: The aim of this study is to investigate the clinical and laboratory characteristics of nonalcoholic fatty liver disease (NAFLD) in a referral center of pediatrics in the northwest of Iran. Methods: In this cross-sectional study all subjects aged between six months to 15 years that were referred to the sonography unit, were investigated for fatty liver from March 2005 to August 2006. Patients with fatty liver change underwent detailed clinical and laboratory evaluation. Results: From 150...

  10. Endovascular management in liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Kyu-Bo Sung

    2006-01-01

    @@ Liver transplantation was developed for the treatment of hepatic failure, and the first human liver transplantation was done in 1963. From the 1990 s,liver transplantation was generally accepted as a treatment modality for both end-stage liver disease and selected liver malignancies. Initially, liver transplantation was started with deceased donor whole-size liver transplantation (whole-size LT) as in other organ transplantation, but there is now a shortage of deceased liver donors has occurred. As a solution, deceased donor split liver transplantation (split LT) began in 1989 and living donor liver transplantation (LDLT) in the early 1990 s. Current liver transplantation techniques include whole-size LT, reduced-size liver transplantation (reduced-size LT), split LT and single or dual LDLT. Two donors give a part of their livers to one adult recipient simultaneously in dual LDLT.

  11. Transjugular liver biopsy.

    Science.gov (United States)

    Ble, Michel; Procopet, Bogdan; Miquel, Rosa; Hernandez-Gea, Virginia; García-Pagán, Juan Carlos

    2014-11-01

    Liver biopsy is still the gold standard for evaluation of acute and chronic liver diseases, despite achievements regarding noninvasive diagnosis and staging in liver diseases. Transjugular liver biopsy (TJLB) has proved a good option when ascites and/or significant coagulopathy precludes a percutaneous approach. Because diagnostic hemodynamic procedures can be performed during the same session, it is useful in many clinical settings, regardless of the absence of percuteaneous contraindications. TJLB is a safe technique able to provide good-quality specimens with a low rate of complications. This article presents an overview of TJLB that discusses the technique, applicability, indications, contraindications, complications, and diagnostic accuracy.

  12. Preliminary experimental study on evaluation of liver injury by ultrasonic targeting imaging%靶向性超声显影评价不同程度肝损伤的初步实验研究

    Institute of Scientific and Technical Information of China (English)

    余进洪; 郑元义; 李奥; 王志刚; 项莹霞

    2011-01-01

    目的 使用靶向超声分子显像对比分析大鼠不同程度急性肝损伤后峰值回声强度的改变与去唾液酸糖蛋白受体(ASGPR)的含量及血清学检查的关系.方法 根据腹腔灌注四氯化碳分析纯的不同剂量(10%、20%、30%、40%、50%),将45只健康雄性SD大鼠随机分为相应5组(组Ⅰ~组Ⅴ),每组9只,每组中再随机抽取4只取肝组织,分别检测ASGPR的含量;另5只仅常规麻醉,胸腹部备皮,经尾静脉团注靶向液态氟碳纳米脂质超声造影剂.从注射开始至0.5 h内连续观察并记录,0.5~1 h内每10 min观察并记录,1 h至造影剂消退每30 min观察并记录肝实质超声图像.DFY型超声图像定量分析诊断仪对各时间点采集到的超声图像进行分析.另选10只健康雄性SD大鼠作为靶向超声造影对照组,方法同前.结果 随着肝损伤程度的增加,肝组织内的ASGPR含量逐渐减少,且各组样本均数两两比较差异均有统计学意义(P0.05).结论 自制靶向肝实质细胞膜受体ASGPR的液态氟碳纳米超声造影剂的肝靶向性显影效果佳;不同程度肝损伤后的靶向超声显影结果改变与ASGPR结果改变一致,有利于超声显影定量评价肝脏功能.%Objective To comparatively analyze the relationship of peak - echo intensity of targeted ultrasound molecular imaging and asialoglycoprotein receptor ( ASGPR) content in different degree of rat acute liver injury. Methods Acute liver injury model was established by intraperitoneal infusion of carbon tetrachloride ( CCl4 ) in 45 healthy male SD rats,the rats were divided int0 5 groups ( group Ⅰ - groupⅤ ) according to doses of CCl4 ( 10% ,20% ,30% ,40% ,50% ) with 9 rats in each group. The content of liver ASGPR in 4 rats of each group was detected respectively. The others were anesthetized generally , thoracic and abdominal skin was prepared, the liquid perfluorocarbon nanoparticles targeted ultrasound contrast agents were injected

  13. Effect of adoptive transfer or depletion of regulatory T cells on triptolide-induced liver injury

    Directory of Open Access Journals (Sweden)

    Xinzhi eWang

    2016-04-01

    Full Text Available ObjectiveThe aim of this study is to clarify the role of regulatory T cell (Treg in triptolide (TP-induced hepatotoxicity. MethodsFemale C57BL/6 mice received either adoptive transfer of Tregs or depletion of Tregs, then underwent TP administration and were sacrificed 24 hours after TP administration. Liver injury was determined according to ALT and AST levels in serum and histopathological change in liver tissue. Hepatic frequencies of Treg cells and the mRNA expression levles of transcription factor FoxP3 and RORγt, IL-10, SOCS and Notch/Notch ligand were investigated.ResultsDuring TP-induced liver injury, hepatic Treg and IL-10 decreased, while Th17 cell transcription factor RORγt, SOCS signaling and Notch signaling increased, accompanied with liver inflammation. Adoptive transfer of Tregs ameliorated the severity of TP-induced liver injury, accompanied with increased levels of hepatic Treg and IL-10. Adoptive transfer of Tregs remarkably inhibited the expression of RORγt, SOCS3, Notch1 and Notch3. On the contrary, depletion of Treg cells in TP-administered mice resulted in a notable increase of RORγt, SOCS1, SOCS3 and Notch3, while the Treg and IL-10 of liver decreased. Consistent with the exacerbation of liver injury, higher serum levels of ALT and AST were detected in Treg-depleted mice. ConclusionsThese results showed that adoptive transfer or depletion of Tregs attenuated or aggravated TP-induced liver injury, suggesting that Tregs could play important roles in the progression of liver injury. SOCS proteins and Notch signaling affected Tregs, which may contribute to the pathogenesis of TP-induced hepatotoxicity.

  14. The impact of hepatic steatosis on liver regeneration after partial hepatectomy

    NARCIS (Netherlands)

    Kele, Petra G.; van der Jagt, Eric J.; Gouw, Annette S. H.; Lisman, Ton; Porte, Robert J.; de Boer, Marieke T.

    2013-01-01

    Background & Aim Experimental studies in animals have suggested that liver regeneration is impaired in steatotic livers. However, few studies have focused on the impact of steatosis in patients undergoing partial hepatectomy (PH). This study aims to determine the role of steatosis on liver regenerat

  15. Liver transplantation in polycystic liver disease

    DEFF Research Database (Denmark)

    Krohn, Paul S; Hillingsø, Jens; Kirkegaard, Preben

    2008-01-01

    OBJECTIVE: Polycystic liver disease (PLD) is a rare, hereditary, benign disorder. Hepatic failure is uncommon and symptoms are caused by mass effects leading to abdominal distension and pain. Liver transplantation (LTX) offers fully curative treatment, but there is still some controversy about...... whether it is a relevant modality considering the absence of liver failure, relative organ shortage, perioperative risks and lifelong immunosuppression. The purpose of this study was to review our experience of LTX for PLD and to compare the survival with the overall survival of patients who underwent LTX....../kidney transplantation. One patient had undergone kidney transplantation 10 years earlier. RESULTS: Median follow-up was 55 months. One patient who underwent combined transplantation died after 5.4 months because of multiorgan failure after re-LTX, and one patient, with well-functioning grafts, died of lymphoma after 7...

  16. Laser treatment for liver metastases : thermal and photodynamic therapy

    OpenAIRE

    van Hillegersberg, Richard

    1993-01-01

    textabstractMedical laser applications are one of the points of interest of the Department of Surgery of the Erasmus University Rotterda._"Il. In 1988. experiments were conducted at the Laboratory for Experimental Surgery to investigate the use of laser in destroying liver metastases. These studies led to the research program "Laser treatment of experimental liver metastases", that was supported by the Netherlands Digestive Disease Foundation from beginning 1990 to the middle of 1992. Within ...

  17. [Hepatic cell transplantation: a new therapy in liver diseases].

    Science.gov (United States)

    Pareja, Eugenia; Cortés, Miriam; Martínez, Amparo; Vila, Juan José; López, Rafael; Montalvá, Eva; Calzado, Angeles; Mir, José

    2010-07-01

    Liver transplantation has been remarkably effective in the treatment in patients with end-stage liver disease. However, disparity between solid-organ supply and increased demand is the greatest limitation, resulting in longer waiting times and increase in mortality of transplant recipients. This situation creates the need to seek alternatives to orthotopic liver transplantation.Hepatocyte transplantation or liver cell transplantation has been proposed as the best method to support patients. The procedure consists of transplanting individual cells to a recipient organ in sufficient quantity to survive and restore the function. The capacity of hepatic regeneration is the biological basis of hepatocyte transplantation. This therapeutic option is an experimental procedure in some patients with inborn errors of metabolism, fulminant hepatic failure and acute and chronic liver failure, as a bridge to orthotopic liver transplantation. In the Hospital La Fe of Valencia, we performed the first hepatocyte transplantation in Spain creating a new research work on transplant program.

  18. Effect of the Human Amniotic Membrane on Liver Regeneration in Rats

    Science.gov (United States)

    Sipahi, Mesut; Şahin, Sevinç; Arslan, Ergin; Börekci, Hasan; Metin, Bayram; Cantürk, Nuh Zafer

    2015-01-01

    Introduction. Operations are performed for broader liver surgery indications for a better understanding of hepatic anatomy/physiology and developments in operation technology. Surgery can cure some patients with liver metastasis of some tumors. Nevertheless, postoperative liver failure is the most feared complication causing mortality in patients who have undergone excision of a large liver mass. The human amniotic membrane has regenerative effects. Thus, we investigated the effects of the human amniotic membrane on regeneration of the resected liver. Methods. Twenty female Wistar albino rats were divided into control and experimental groups and underwent a 70% hepatectomy. The human amniotic membrane was placed over the residual liver in the experimental group. Relative liver weight, histopathological features, and biochemical parameters were assessed on postoperative day 3. Results. Total protein and albumin levels were significantly lower in the experimental group than in the control group. No difference in relative liver weight was observed between the groups. Hepatocyte mitotic count was significantly higher in the experimental group than in the control group. Hepatic steatosis was detected in the experimental group. Conclusion. Applying the amniotic membrane to residual liver adversely affected liver regeneration. However, mesenchymal stem cell research has the potential to accelerate liver regeneration investigations. PMID:26457000

  19. Effect of the Human Amniotic Membrane on Liver Regeneration in Rats

    Directory of Open Access Journals (Sweden)

    Mesut Sipahi

    2015-01-01

    Full Text Available Introduction. Operations are performed for broader liver surgery indications for a better understanding of hepatic anatomy/physiology and developments in operation technology. Surgery can cure some patients with liver metastasis of some tumors. Nevertheless, postoperative liver failure is the most feared complication causing mortality in patients who have undergone excision of a large liver mass. The human amniotic membrane has regenerative effects. Thus, we investigated the effects of the human amniotic membrane on regeneration of the resected liver. Methods. Twenty female Wistar albino rats were divided into control and experimental groups and underwent a 70% hepatectomy. The human amniotic membrane was placed over the residual liver in the experimental group. Relative liver weight, histopathological features, and biochemical parameters were assessed on postoperative day 3. Results. Total protein and albumin levels were significantly lower in the experimental group than in the control group. No difference in relative liver weight was observed between the groups. Hepatocyte mitotic count was significantly higher in the experimental group than in the control group. Hepatic steatosis was detected in the experimental group. Conclusion. Applying the amniotic membrane to residual liver adversely affected liver regeneration. However, mesenchymal stem cell research has the potential to accelerate liver regeneration investigations.

  20. Expression and distribution of connexin 32 in rat liver with experimentally induced fibrosis Expressão e distribuição da conexina 32 em fígados de ratos com fibrose induzida experimentalmente

    Directory of Open Access Journals (Sweden)

    Alexandro dos S. Rodrigues

    2009-04-01

    Full Text Available The connexin 32 (Cx32 is a protein that forms the channels that promote the gap junction intercellular communication (GJIC in the liver, allowing the diffusion of small molecules through cytosol from cell-to-cell. Hepatic fibrosis is characterized by a disruption of normal tissue architeture by cellular lesions, and may alter the GJIC. This work aimed to study the expression and distribution of Cx32 in liver fibrosis induced by the oral administration of dimethylnitrosamine in female Wistar rats. The necropsy of the rats was carried out after five weeks of drug administration. They presented a hepatic fibrosis state. Sections from livers with fibrosis and from control livers were submitted to immunohistochemical, Real Time-PCR and Western-Blot analysis to Cx32. In fibrotic livers the Cxs were diffusely scattered in the cytoplasm, contrasting with the control livers, where the Cx32 formed junction plaques at the cell membrane. Also it was found a decrease in the gene expression of Cx32 without reduction in the protein quantity when compared with controls. These results suggest that there the mechanism of intercellular communication between hepatocytes was reduced by the fibrotic process, which may predispose to the occurrence of a neoplastic process, taken in account that connexins are considered tumor suppressing genes.A conexina 32 (Cx32 é uma proteína que constitui os canais que promovem as comunicações intercelulares via junções comunicantes (CIJC no fígado, permitindo difusão de pequenas moléculas citoplasmáticas de uma célula à outra. A fibrose hepática caracteriza-se pela alteração da arquitetura normal do fígado e podem alterar as CIJCs. O objetivo deste trabalho foi estudar a expressão e distribuição de Cx32 na fibrose hepática. O objetivo do presente trabalho foi estudar a expressão e distribuição da Cx32 em fígados com fibrose induzida pela administração oral de dimetilnitrosamina em fêmeas de ratos Wistar. A

  1. Bioartificial Liver Support

    Directory of Open Access Journals (Sweden)

    Vincent G Bain

    2001-01-01

    Full Text Available Bioartificial liver support has been increasingly the focus of both basic and clinical research in an attempt to replicate the multiplicity of normal liver function. The concept is attractive because, if it is effective, patients with acute liver failure may be supported until native liver regeneration occurs or, by optimizing their condition, until liver transplantation is possible. Current bioartificial liver support systems utilize primary porcine hepatocytes or transformed human hepatocytes, which are housed within a bioreactor, through which the patient's blood or plasma is pumped in an extracorporeal circuit. The optimal source for the hepatocytes is an area of debate; however, a genetically engineered cell line may provide optimal function. Novel three-dimensional matrices that anchor the hepatocytes are being designed to mimic architectural features of the normal liver. Large multicentre, randomized, controlled trials are ongoing following several pilot studies. Serious side effects such as hemodynamic instability and immune reactions have been infrequent. Much controversy, however, surrounds the issue of possible transmission of pig endogenous retrovirus to humans, and current trials are being carefully monitored. Bioartificial liver support is a promising technology, and the results of current and planned studies are awaited with great interest.

  2. Liver and Biliary System

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    9.1.Liver cirrhosis and fatty liver2005376 The role of ribosomal S6 kinase in thepathogenesis of rat hepatic fibrosis.YANG Miaofang(杨妙芳),et al.Dept Gastroenterol,Changzheng Hosp,2nd Milit Med Univ,Shanghai 200003.Chin J Dig 2005;25(2):98-100.

  3. Prolactin and liver disease

    NARCIS (Netherlands)

    A.G.C. Bauer (Alexander)

    1982-01-01

    textabstractCirrhosis of the liver is associated with profound endocrinological disturbances. Until recently it was thought that these disturbances were caused mainly by ineffective elimination of hormones by the diseased liver. It is now known that the pathogenesis of disturbed hormonal function in

  4. LIVER AND BILIARGY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    8.1 Liver cirrhosis and fatty liver2004100 The clinical feature and prognosis of Aero-monas septicaemia in hepatic cirrhosis: a report of 50 cases. QU Fen (曲芬), et al. Clin Centre, 302nd Hosp PLA, Beijing 100039. Chin J Intern Med 2003; 42 (12): 840 - 846Objective: Aeromonas septicaemia complicating cirrhosis

  5. Hypoxia and fatty liver.

    Science.gov (United States)

    Suzuki, Tomohiro; Shinjo, Satoko; Arai, Takatomo; Kanai, Mai; Goda, Nobuhito

    2014-11-07

    The liver is a central organ that metabolizes excessive nutrients for storage in the form of glycogen and lipids and supplies energy-producing substrates to the peripheral tissues to maintain their function, even under starved conditions. These processes require a considerable amount of oxygen, which causes a steep oxygen gradient throughout the hepatic lobules. Alcohol consumption and/or excessive food intake can alter the hepatic metabolic balance drastically, which can precipitate fatty liver disease, a major cause of chronic liver diseases worldwide, ranging from simple steatosis, through steatohepatitis and hepatic fibrosis, to liver cirrhosis. Altered hepatic metabolism and tissue remodeling in fatty liver disease further disrupt hepatic oxygen homeostasis, resulting in severe liver hypoxia. As master regulators of adaptive responses to hypoxic stress, hypoxia-inducible factors (HIFs) modulate various cellular and organ functions, including erythropoiesis, angiogenesis, metabolic demand, and cell survival, by activating their target genes during fetal development and also in many disease conditions such as cancer, heart failure, and diabetes. In the past decade, it has become clear that HIFs serve as key factors in the regulation of lipid metabolism and fatty liver formation. This review discusses the molecular mechanisms by which hypoxia and HIFs regulate lipid metabolism in the development and progression of fatty liver disease.

  6. Liver and Biliary System

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    2011220 Value of liver biopsy in diagnosis of chronic hepatitis B. YANG Fang(杨方) ,et al. 2nd Ward, Shenyang 6th People’s Hosp,Shenyang 110006. Chin J Infect Dis 2011; 29(2):99-103. Objective To explore the value of liver biopsy in diagnosis of the severity of chronic hepatitis

  7. Acute liver failure

    DEFF Research Database (Denmark)

    Bernal, William; Lee, William M; Wendon, Julia;

    2015-01-01

    Over the last three decades acute liver failure (ALF) has been transformed from a rare and poorly understood condition with a near universally fatal outcome, to one with a well characterized phenotype and disease course. Complex critical care protocols are now applied and emergency liver...

  8. Multiple pyogenic liver abscess

    Institute of Scientific and Technical Information of China (English)

    Mabrouk Bahloul; Anis Chaari; Nadia Bouaziz-Khlaf; Hatem Kallel; Leila Herguefi; Hedi Chelly; Chokri Ben Hamida; Mounir Bouaziz

    2006-01-01

    Multiple pyogenic liver abscesses have been rarely described. We report a fatal case of multiple pyogenic liver abscesses affecting a 38-year-old woman requiring surgical drainage. Evolution was marked by occurrence of a septic shock with multi-organ system failure. The patient died 48 h after surgery. Causes, therapeutics and outcome of the disease are discussed.

  9. Stage scoring of liver fibrosis using Mueller matrix microscope

    Science.gov (United States)

    Zhou, Jialing; He, Honghui; Wang, Ye; Ma, Hui

    2016-10-01

    Liver fibrosis is a common pathological process of varied chronic liver diseases including alcoholic hepatitis, virus hepatitis, and so on. Accurate evaluation of liver fibrosis is necessary for effective therapy and a five-stage grading system was developed. Currently, experienced pathologists use stained liver biopsies to assess the degree of liver fibrosis. But it is difficult to obtain highly reproducible results because of huge discrepancy among different observers. Polarization imaging technique has the potential of scoring liver fibrosis since it is capable of probing the structural and optical properties of samples. Considering that the Mueller matrix measurement can provide comprehensive microstructural information of the tissues, in this paper, we apply the Mueller matrix microscope to human liver fibrosis slices in different fibrosis stages. We extract the valid regions and adopt the Mueller matrix polar decomposition (MMPD) and Mueller matrix transformation (MMT) parameters for quantitative analysis. We also use the Monte Carlo simulation to analyze the relationship between the microscopic Mueller matrix parameters and the characteristic structural changes during the fibrosis process. The experimental and Monte Carlo simulated results show good consistency. We get a positive correlation between the parameters and the stage of liver fibrosis. The results presented in this paper indicate that the Mueller matrix microscope can provide additional information for the detections and fibrosis scorings of liver tissues and has great potential in liver fibrosis diagnosis.

  10. Over-starvation aggravates intestinal injury and promotes bacterial and endotoxin translocation under high-altitude hypoxic environment

    Institute of Scientific and Technical Information of China (English)

    Qi-Quan Zhou; Ding-Zhou Yang; Yong-Jun Luo; Su-Zhi Li; Fu-Yu Liu; Guan-Song Wang

    2011-01-01

    AIM: To study whether over-starvation aggravates intestinal mucosal injury and promotes bacterial and endotoxin translocation in a high-altitude hypoxic environment. METHODS: Sprague-Dawley rats were exposed to hypobaric hypoxia at a simulated altitude of 7000 m for 72 h. Lanthanum nitrate was used as a tracer to detect intestinal injury. Epithelial apoptosis was observed with terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Serum levels of diamino oxidase (DAO), malondialdehyde (MDA), glutamine (Gln), superoxide dismutase (SOD) and endotoxin were measured in intestinal mucosa. Bacterial translocation was detected in blood culture and intestinal homogenates. In addition, rats were given Gln intragastrically to observe its protective effect on intestinal injury. RESULTS: Apoptotic epithelial cells, exfoliated villi and inflammatory cells in intestine were increased with edema in the lamina propria accompanying effusion of red blood cells. Lanthanum particles were found in the intercellular space and intracellular compartment. Bacterial translocation to mesenteric lymph nodes (MLN) and spleen was evident. The serum endotoxin, DAO and MDA levels were significantly higher while the serum SOD, DAO and Gln levels were lower in intestine (P < 0.05). The bacterial translocation number was lower in the high altitude hypoxic group than in the high altitude starvation group (0.47 ± 0.83 vs 2.38 ± 1.45, P < 0.05). The bacterial translocation was found in each organ, especially in MLN and spleen but not in peripheral blood. The bacterial and endotoxin translocations were both markedly improved in rats after treatment with Gln. CONCLUSION: High-altitude hypoxia and starvation cause severe intestinal mucosal injury and increase bacterial and endotoxin translocation, which can be treated with Gln.

  11. Aggravation of north channels' shrinkage and south channels' development in the Yangtze Estuary under dam-induced runoff discharge flattening

    Science.gov (United States)

    Zhu, Bo-yuan; Li, Yi-tian; Yue, Yao; Yang, Yun-ping

    2017-03-01

    Construction of dams on rivers has progressively affected the seasonal variability of runoff discharge, which has consequently produced remarkable impacts on the morphology of estuarine channels. This paper considers four-typical-order bifurcations of the Yangtze Estuary and adopts an ebb partition ratio (defined as the diversion ratio of ebb flow in a given branch divided by the total ebb tidal discharge immediately upstream of the river node where the bifurcation occurs) as a measure of water excavating force in the bifurcation channels. Results show that the seasonal variability of runoff discharge at Datong Hydrological Station (Datong) is flattened, being mainly driven by upstream runoff flattening observed at Yichang Hydrological Station (Yichang) and the tributary rivers. Yearly ebb partition ratios of the channels located to the north and south of the islands present decreasing and increasing trends respectively, and as also do the yearly north and south channel volume of the bifurcations. Yearly ebb partition ratio is proved to be an effective index to represent the water excavating force considering the stability of yearly ebb tidal discharge and its relationship with the channel erosion-deposition. River dams are the driving factors behind the runoff flattening at Datong because of their flattening effects on its main contributors (Yichang and tributary rivers). This flattening significantly helps reduce and enlarge the yearly ebb partition ratios of the north and south channels respectively, and then aggravates the shrinkage and development of the north and south channels separately. Yearly ebb partition ratio of the North Passage (NP) must be enlarged in order for the NP to maintain its function as a shipping channel.

  12. Extracellular heat-shock protein 70 aggravates cerulein-induced pancreatitis through toll-like receptor-4 in mice

    Institute of Scientific and Technical Information of China (English)

    SONG Jun-min; WANG Rong; LIU Hong-xiang; LI Yuan; ZENG Yu-jian; ZHOU Zong-guang; LIU Hai-yi; XU Bing; WANG Ling; ZHOU Bin

    2008-01-01

    Background In patients suffering from acute pancreatitis, the pathogenesis is not completely understood, and several recent studies in vitro suggested that heat shock proteins might play an important role in cell signaling. To investigate the possible role of extracellular heat shock protein 70 (Hsp70) in pancreatitis, toll-like receptor-4 (TLR4)-deficient and wild-type mice were administered with exogenous Hsp70 during the course of cerulein-induced pancreatitis (CIP).Methods Acute pancreatitis was induced by 5 intraperitoneal injections of cerulein at hourly intervals, and then treated with recombinant Hsp70 through the caudal vein 4 hours after the start of cerulein injections. Subsequently serum amylase and serum cytokines levels were detected. Histologic alteration of the pancreas was evaluated. Tumor necrosis factor alpha (TNF-a) concentrations and myeloperoxidase (MPO) activity in both pancreas and lungs were analyzed. The nuclear factor kappa B (NF-KB) activation in pancreatic tissue was measured using a sensitive RelA enzyme-linked immunosorbent assay.Results Treatment with recombinant Hsp70 to wild-type mice in CIP resulted in significant aggravation of inflammation in pancreas, elevated levels of serum cytokines, up-regulation of pulmonary MPO activity and increase of lung tissues TNF-α concentrations. In contrast, treatment with Hsp70 to TLR4-deficient mice had little effect on serum cytokines levels, pancreatic inflammation, pulmonary MPO activity and TNF-a concentrations.Conclusions The results suggest that extracellular HspTO might induce systemic inflammatory response syndrome (SIRS)-Iike response in vivo and TLR4 might be involved in the Hsp70-mediated activation of inflammatory reaction in the progression of CIP without infection.

  13. Inhibition of JNK aggravates the recovery of rat hearts after global ischemia: the role of mitochondrial JNK.

    Directory of Open Access Journals (Sweden)

    Sehwan Jang

    Full Text Available c-Jun N-terminal kinase (JNK, a stress-activated MAPK, is activated during cardiac ischemia-reperfusion (IR. The role of JNK inhibitors in cardioprotection against IR still remains controversial, in part, due to spill-over effects of non-specific inhibitors. In the present study, we sought to examine whether inhibition of JNK by SU3327, a specific JNK inhibitor that inhibits upstream JNK signaling rather than the kinase activity of JNK, improves cardiac function and reduces heart damage during IR. Hearts of male Sprague-Dawley rats perfused by Langendorff were subjected to 25 min of global ischemia followed by 30 min reperfusion in the presence or absence of SU3327. Cardiac function was monitored throughout the perfusion period. Myocardial damage was extrapolated from LDH activity in the coronary effluent. At the end of reperfusion, mitochondria were isolated and used to measure respiration rates and mitochondrial permeability transition pore opening. Protein analysis of mitochondria predictably revealed that SU3327 inhibited JNK phosphorylation. Although SU3327 significantly reduced cell damage during the first minutes of reperfusion, it did not improve cardiac function and, furthermore, reduced the mitochondrial respiratory control index. Interestingly, SU3327 activated the other stress-related MAPK, p38, and greatly increased its translocation to mitochondria. Mitochondrial P-JNK and P-p38 were co-immunoprecipitated with complex III of the electron transfer chain. Thus, JNK plays an essential role in cardiac signaling under both physiological and pathological conditions. Its inhibition by SU3327 during IR aggravates cardiac function. The detrimental effects of JNK inhibition are associated with reciprocal p38 activation and mitochondrial dysfunction.

  14. High-sodium intake aggravates myocardial injuriesinduced by aldosterone via oxidative stress inSprague-Dawley rats

    Institute of Scientific and Technical Information of China (English)

    Jing-yi LI; Shao-ling ZHANG; Meng REN; Yan-ling WEN; Li YAN; Hua CHENG

    2012-01-01

    To evaluate the effects of aldosterone with or without high sodium intake on blood pressure,myocardial structure and left ventricular function in rats,and to investigate the mechanisms underlying the effects.Methods:Eight-week-old male Sprague-Dawley rats were randomly divided into 3 groups:(1) control (CON) group fed a normal sodium diet,(2) aldosterone (ALD) group receiving aldosterone infusion and a normal sodium diet,and (3) high sodium plus aldosterone (HS-ALD) group receiving 1% NaCl diet in conjunction with aldosterone infusion.Aldosterone was administered through continuously subcutaneous infusion with osmotic minipump at the rate of 0.75 μg/h for 8 weeks.The myocardium structure was observed using transt-horacic echocardiography and transmission electron microscopy.The collagen deposition in left ventricle was evaluated with Masson'strichrome staining.The expression of IL-18,p22phox,and p47phox proteins was examined using Western blot analysis.Results:The systolic blood pressure in the ALD and HS-ALD groups was significantly higher than that in the CON group after 2-week treatment.But the blood pressure showed no significant difference between the HS-ALD and ALD groups.The left ventricular hyper-trophy,myocardial collagen deposition and oxidative stress were predominantly found in the HS-ALD and ALD group.Furthermore,the breakdown of myocardial structure and oxidative stress were more apparent in the HS-ALD group as compared with those in the ALDgroup.Conclusion:Long-term infusion of aldosterone results in hypertension and profibrotic cardiovascular responses in rats fed a normal sodium diet,which were mediated by oxidative stress.High-sodium intake could aggravate myocardial injuries induced by aldosterone.

  15. Liver cancer oncogenomics

    DEFF Research Database (Denmark)

    Marquardt, Jens U; Andersen, Jesper B

    2015-01-01

    Primary liver cancers are among the most rapidly evolving malignant tumors worldwide. An underlying chronic inflammatory liver disease, which precedes liver cancer development for several decades and frequently creates a pro-oncogenic microenvironment, impairs progress in therapeutic approaches....... Molecular heterogeneity of liver cancer is potentiated by a crosstalk between epithelial tumor and stromal cells that complicate translational efforts to unravel molecular mechanisms of hepatocarcinogenesis with a drugable intend. Next-generation sequencing has greatly advanced our understanding of cancer...... development. With regards to liver cancer, the unprecedented coverage of next-generation sequencing has created a detailed map of genetic alterations and identified key somatic changes such as CTNNB1 and TP53 as well as several previously unrecognized recurrent disease-causing alterations that could...

  16. Comparing Effects of Medication Therapy and Exercise Training with Diet on Liver enzyme Levels and Liver Sonography in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD

    Directory of Open Access Journals (Sweden)

    Azadeh Nabizadeh Haghighi

    2016-03-01

    Full Text Available Background & Objectives: Non-alcoholic fatty liver disease, characterized by the deposition of fat in liver cells, can cause fibrosis, cirrhosis, and liver cell damage if not controlled. The aim of this study is to compare the effects of medication therapy and exercise training with diet on liver enzyme levels and liver sonography in patients with non-alcoholic fatty liver disease (NAFLD. Materials & Methods :In this quasi-experimental study, female patients with non-alcoholic fatty liver were randomly divided into two groups: medication therapy (n = 10 and exercise therapy (n = 10 for 8 weeks. During this period, the exercise group performed exercise training three days a week for 90 minutes per session. The drug was given to the medication group. In both groups, the diet was 500 calories less than their daily energy. Before and after intervention, blood tests and liver sonography were executed. All statistical analyses were done using SPSS for Windows version 20. Comparisons between and within groups were performed by Student's t-test and Wilcoxon test on paired and unpaired data. P < 0.05 was considered statistically significant. Results :In both groups, liver enzyme levels and disease severity in sonography reduced significantly (p<0.05. Conclusion: The findings of the present research showed that both methods of therapy have the same effect on reducing the severity of NAFLD.

  17. Signal Transduction of Platelet-Induced Liver Regeneration and Decrease of Liver Fibrosis

    Directory of Open Access Journals (Sweden)

    Soichiro Murata

    2014-03-01

    Full Text Available Platelets contain three types of granules: alpha granules, dense granules, and lysosomal granules. Each granule contains various growth factors, cytokines, and other physiological substances. Platelets trigger many kinds of biological responses, such as hemostasis, wound healing, and tissue regeneration. This review presents experimental evidence of platelets in accelerating liver regeneration and improving liver fibrosis. The regenerative effect of liver by platelets consists of three mechanisms; i.e., the direct effect on hepatocytes, the cooperative effect with liver sinusoidal endothelial cells, and the collaborative effect with Kupffer cells. Many signal transduction pathways are involved in hepatocyte proliferation. One is activation of Akt and extracellular signal-regulated kinase (ERK1/2, which are derived from direct stimulation from growth factors in platelets. The other is signal transducer and activator of transcription-3 (STAT3 activation by interleukin (IL-6 derived from liver sinusoidal endothelial cells and Kupffer cells, which are stimulated by contact with platelets during liver regeneration. Platelets also improve liver fibrosis in rodent models by inactivating hepatic stellate cells to decrease collagen production. The level of intracellular cyclic adenosine monophosphate (cyclic AMP is increased by adenosine through its receptors on hepatic stellate cells, resulting in inactivation of these cells. Adenosine is produced by the degradation of adenine nucleotides such as adenosine diphosphate (ADP and adenosine tri-phosphate (ATP, which are stored in abundance within the dense granules of platelets.

  18. Intraoperative blood loss in orthotopic liver transplantation:The predictive factors

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Liver transplantation has been associated with massiveblood loss and considerable transfusion requirements.Bleeding in orthotopic liver transplantation is multifactorial.Technical difficulties inherent to this complex surgicalprocedure and pre operative derangements of the primaryand secondary coagulation system are thought tobe the principal causes of perioperative hemorrhage.Intraoperative practices such as massive fluid resuscitationand resulting hypothermia and hypocalcemia secondaryto citrate toxicity further aggravate the preexistingcoagulopathy and worsen the perioperative bleeding.Excessive blood loss and transfusion during orthotopicliver transplant are correlated with diminished graftsurvival and increased septic episodes and prolongedICU stay. With improvements in surgical skills, anesthetictechnique, graft preservation, use of intraoperative cellsavers and overall perioperative management, orthotopicliver transplant is now associated with decreased intraoperative blood losses. The purpose of this review isto discuss the risk factors predictive of increased intraoperative bleeding in patients undergoing orthotopic livertransplant.

  19. Antioxidant supplements for liver diseases

    DEFF Research Database (Denmark)

    Bjelakovic, Goran; Gluud, Lise Lotte; Nikolova, Dimitrinka

    2011-01-01

    Several liver diseases have been associated with oxidative stress. Accordingly, antioxidants have been suggested as potential therapeutics for various liver diseases. The evidence supporting these suggestions is equivocal....

  20. Liver biopsy in liver patients with coagulopathy

    DEFF Research Database (Denmark)

    Ott, P.; Gronbaek, H.; Clausen, M.R.;

    2008-01-01

    The risk of severe bleeding after liver biopsy is estimated to be 1:12,000 in patients with near normal coagulation (INR 60 billion /l). Beyond these limits, the risk is higher, but still uncertain. The Danish guidelines require INR > 1.5, platelet count

  1. Liver Transplant Tolerance and Its Application to the Clinic: Can We Exploit the High Dose Effect?

    OpenAIRE

    Cunningham, Eithne C.; Sharland, Alexandra F.; G. Alex Bishop

    2013-01-01

    The tolerogenic properties of the liver have long been recognised, especially in regard to transplantation. Spontaneous acceptance of liver grafts occurs in a number of experimental models and also in a proportion of clinical transplant recipients. Liver graft acceptance results from donor antigen-specific tolerance, demonstrated by the extension of tolerance to other grafts of donor origin. A number of factors have been proposed to be involved in liver transplant tolerance induction, includi...

  2. 丹红注射液对大鼠50%同种异体肝移植影响的实验研究%Experimental study of Danhong Injection on rat after 50%allogeneic liver transplantation

    Institute of Scientific and Technical Information of China (English)

    李翠芳; 郭萍; 陈德森; 李贤玉; 姚远; 郭俐宏

    2015-01-01

    Objective It is to observe effect of Danhong injection on hepatic viability and enzyme activity in rats after 50%reduced size orthotopic liver transplantation, and provide a theoretical basis for clinical rational drug use.Methods 30 rats were selected and randomly divided into model group, small dose Danhong group, high dose Danhong group, using modified double cuff method to establish animal model of 50% rat orthotopic reduced size orthotopic liver transplantation, another 10 rats were chosen as blank control group.Small dose Danhong group and high dose Danhong group were treated with Danhong Injection by the tail vein injection for 14 days.Before and after treatment, the activities of 5 kinds of subtypes of enzyme in rat liver microsomal cytochrome ( CYPIA2, CYP2C9, CYP2D6, CYP2E1, CYP3A4), the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilTMGubin (TBil) were determined, survival rate of liver transplanta-tion recipient rats were counted.Results The activities of rat liver microsomal CYPIA2, CYP2C9, CYP3A4 and the levels of ALT, AST were lower in small dose Danhong group and high dose Danhong grouop than those in model group, the survival rate was 70%in Danhong Injection groups, compared with the model group, the differences were all statistically significant (P all<0.05) , but there was no significant difference between the two Danhong Injection groups.Conclusion Danhong Injection can increase survival rate of the rats after 50%reduced size orthotopic liver, inhibit the activities of CYPIA2、CYP2C9、CYP3A4 in rat liver microsomes, promote the recovery of liver function.%目的:观察丹红注射液对大鼠50%减体积原位肝移植术后存活及酶活性的影响,为临床合理用药提供理论依据。方法选择30对大鼠,随机分为模型组、丹红小剂量组、丹红大剂量组,采用改良双袖套法建立50%大鼠同种异体减体积原位肝脏移植动物模型,另设10只为空白

  3. 逍遥散对肝纤维化大鼠模型抗纤维化作用及其机制研究%Anti-fibrosis Effect and Mechanism of Xiaoyao Powder on Experimental Liver Fibrosis Rat Model

    Institute of Scientific and Technical Information of China (English)

    陈曦; 牟璐璐; 陈丹丹; 张春胜; 刘海洋; 李绍民; 张宁

    2014-01-01

    目的:研究逍遥散对四氯化碳(CCl4)致大鼠肝纤维化的干预作用机制。方法将30只大鼠随机分为空白对照组、模型组、逍遥散组。除空白对照组外,均采用皮下注射CCl4橄榄油溶液制备肝纤维化模型,逍遥散组同时灌胃给予逍遥散水煎液。检测大鼠肝匀浆中超氧化物歧化酶(SOD)、丙二醛(MDA)以及血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、白蛋白(ALB)、总蛋白(TP)、总胆红素(TBIL)、转化生长因子β1(TGF-β1)、肿瘤坏死因子α(TNF-α)、人基质金属蛋白酶组织抑制因子-1(TIMP-1)、血小板衍生生长因子(PDGF)、白介素6(IL-6)、透明质酸(HA)、层粘蛋白(LN)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(C-Ⅳ)的含量,并进行肝组织病理学检查。结果与模型组比较,逍遥散能显著降低MDA、 ALT、 AST、 TBIL、 TGF-β1、TNF-α、 TIMP-1、 PDGF、 IL-6、 HA、 LN、 PCⅢ、 C-Ⅳ水平(P<0.05, P<0.01),明显升高SOD、 ALB、 TP水平(P<0.05, P<0.01)。组织病理检查显示,逍遥散能减轻肝细胞变性、坏死、炎性浸润,促进肝细胞再生。结论逍遥散具有抗肝纤维化的作用,其作用机制可能是抑制胶原纤维蛋白的合成与分泌,清除自由基,减少脂质过氧化,促进肝细胞再生,加快肝细胞修复。%Objective To research the intervention mechanism of Xiaoyao Powder on rats with liver fibrosis induced by carbon tetrachloride(CCl4). Methods Rat liver fibrosis model was established by subcutaneous injection of 40% CCl 4 olive oil solution for 9 continuous weeks, and was given Xiaoyao Powder at the same time. After intervention, we observed the superoxide dismutase (SOD) and malondialdehyde (MDA) activities in liver homogenate, and detected serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), albumin(ALB), total

  4. Accelerated CCl4-induced liver fibrosis in Hjv-/- mice, associated with an oxidative burst and precocious profibrogenic gene expression.

    Directory of Open Access Journals (Sweden)

    Giada Sebastiani

    Full Text Available Hereditary hemochromatosis is commonly associated with liver fibrosis. Likewise, hepatic iron overload secondary to chronic liver diseases aggravates liver injury. To uncover underlying molecular mechanisms, hemochromatotic hemojuvelin knockout (Hjv-/- mice and wild type (wt controls were intoxicated with CCl(4. Hjv-/- mice developed earlier (by 2-4 weeks and more acute liver damage, reflected in dramatic levels of serum transaminases and ferritin and the development of severe coagulative necrosis and fibrosis. These responses were associated with an oxidative burst and early upregulation of mRNAs encoding α1-(I-collagen, the profibrogenic cytokines TGF-β1, endothelin-1 and PDGF and, notably, the iron-regulatory hormone hepcidin. Hence, CCl4-induced liver fibrogenesis was exacerbated and progressed precociously in Hjv-/- animals. Even though livers of naïve Hjv-/- mice were devoid of apparent pathology, they exhibited oxidative stress and immunoreactivity towards α-SMA antibodies, a marker of hepatic stellate cells activation. Furthermore, they expressed significantly higher (2-3 fold vs. wt, p<0.05 levels of α1-(I-collagen, TGF-β1, endothelin-1 and PDGF mRNAs, indicative of early fibrogenesis. Our data suggest that hepatic iron overload in parenchymal cells promotes oxidative stress and triggers premature profibrogenic gene expression, contributing to accelerated onset and precipitous progression of liver fibrogenesis.

  5. Cytokines and Liver Diseases

    Directory of Open Access Journals (Sweden)

    Herbert Tilg

    2001-01-01

    Full Text Available Cytokines are pleiotropic peptides produced by virtually every nucleated cell in the body. In most tissues, including the liver, constitutive production of cytokines is absent or minimal. There is increasing evidence that several cytokines mediate hepatic inflammation, apoptosis and necrosis of liver cells, cholestasis and fibrosis. Interestingly, the same mediators also mediate the regeneration of liver tissue after injury. Among the various cytokines, the proinflammatory cytokine tumour necrosis factor-alpha (TNF-a has emerged as a key factor in various aspects of liver disease, such as cachexia and/or cholestasis. Thus, antagonism of TNF-a and other injury-related cytokines in liver diseases merits evaluation as a treatment of these diseases. However, because the same cytokines are also necessary for the regeneration of the tissue after the liver has been injured, inhibition of these mediators might impair hepatic recovery. The near future will bring the exiting clinical challenge of testing new anticytokine strategies in various liver diseases.

  6. A case report of congenital umbilical arteriovenous malformation complicated with liver failure after surgical excision

    Science.gov (United States)

    Han, Ji-Won; Kim, Hyun-Young; Jung, Sung-Eun

    2017-01-01

    Abstract Rationale: Few case reports of umbilical arteriovenous malformation (AVM) have been reported. Herein, we report a neonatal case of umbilical AVM who underwent liver failure after surgical excision. Patient concerns: The patient was a girl delivered at a gestational age of 39+5 weeks showing cyanosis and heart murmur. Diagnoses: Cardiac echography, abdominal ultrasonography (USG), and computed tomography revealed suspecting the umbilical AVM. Interventions: On the eighth day after birth, because of the aggravation of heart failure, emergency surgery for excision of umbilical AVM was performed. Outcomes: In postoperative state, worsened laboratory test of liver function and coagulopathy indicated the liver failure. Abdominal USG revealed that the portal vein (PV) flow primarily occurred from the left PV to the inferior vena cava via ductus venosus and coarse hepatic echogenicity. After conservative management, laboratory findings of liver function and the flow direction of the left PV were normal, as demonstrated by abdominal USG within 50th postoperative day. Lessons: Careful preoperative evaluation of an AVM of a large size with significant blood flow should be performed, and the possibility of liver failure after surgery should always be considered. PMID:28178121

  7. Butyrate protects rat liver against total hepatic ischemia reperfusion injury with bowel congestion.

    Directory of Open Access Journals (Sweden)

    Bin Liu

    Full Text Available Hepatic ischemia/reperfusion (I/R injury is an unavoidable consequence of major liver surgery, especially in liver transplantation with bowel congestion, during which endotoxemia is often evident. The inflammatory response aggravated by endotoxin after I/R contributes to liver dysfunction and failure. The purpose of the present study was to investigate the protective effect of butyrate, a naturally occurring four-carbon fatty acid in the body and a dietary component of foods such as cheese and butter, on hepatic injury complicated by enterogenous endotoxin, as well as to examine the underlying mechanisms involved. SD rats were subjected to a total hepatic ischemia for 30 min after pretreatment with either vehicle or butyrate, followed by 6 h and 24 h of reperfusion. Butyrate preconditioning markedly improved hepatic function and histology, as indicated by reduced transaminase levels and ameliorated tissue pathological changes. The inflammatory factors levels, macrophages activation, TLR4 expression, and neutrophil infiltration in live were attenuated by butyrate. Butyrate also maintained the intestinal barrier structures, reversed the aberrant expression of ZO-1, and decreased the endotoxin translocation. We conclude that butyrate inhibition of endotoxin translocation, macrophages activation, inflammatory factors production, and neutrophil infiltration is involved in the alleviation of total hepatic I/R liver injury in rats. This suggests that butyrate should potentially be utilized in liver transplantation.

  8. Elastin in the Liver

    Directory of Open Access Journals (Sweden)

    Jiri Kanta

    2016-10-01

    Full Text Available A characteristic feature of liver cirrhosis is the accumulation of large amounts of connective tissue with the prevailing content of type I collagen. Elastin is a minor connective tissue component in normal liver but it is actively synthesized by hepatic stellate cells and portal fibroblasts in diseased liver. The accumulation of elastic fibers in later stages of liver fibrosis may contribute to the decreasing reversibility of the disease with advancing time. Elastin is formed by polymerization of tropoelastin monomers. It is an amorphous protein highly resistant to the action of proteases that forms the core of elastic fibers. Microfibrils surrounding the core are composed of fibrillins that bind a number of proteins involved in fiber formation. They include microfibril-associated glycoproteins (MAGPs, microfibrillar-associated proteins (MFAPs and fibulins. Lysyl oxidase (LOX and lysyl oxidase-like proteins (LOXLs are responsible for tropoelastin cross-linking and polymerization. TGF-β complexes attached to microfibrils release this cytokine and influence the behavior of the cells in the neighborhood. The role of TGF-β as the main profibrotic cytokine in the liver is well-known and the release of the cytokines of TGF-β superfamily from their storage in elastic fibers may affect the course of fibrosis. Elastic fibres are often studied in the tissues where they provide elasticity and resilience but their role is no longer viewed as purely mechanical. Tropoelastin, elastin polymer and elastin peptides resulting from partial elastin degradation influence fibroblastic and inflammatory cells as well as angiogenesis. A similar role may be performed by elastin in the liver. This article reviews the results of the research of liver elastic fibers on the backgound of the present knowledge of elastin biochemistry and physiology. The regulation of liver elastin synthesis and degradation may be important for the outcome of liver fibrosis.

  9. Inducible chondrocyte-specific overexpression of BMP2 in young mice results in severe aggravation of osteophyte formation in experimental OA without altering cartilage damage

    NARCIS (Netherlands)

    Davidson, E.N.; Vitters, E.L.; Bennink, M.B.; Lent, P.L. van; Caam, A.P. van; Blom, A.B.; Berg, W.B. van den; Loo, F.A.J. van de; Kraan, P.M. van der

    2015-01-01

    OBJECTIVES: In osteoarthritis (OA) chondrocytes surrounding lesions express elevated bone morphogenetic protein 2 (BMP2) levels. To investigate the functional consequence of chondrocyte-specific BMP2 expression, we made a collagen type II dependent, doxycycline (dox)-inducible BMP2 transgenic mouse

  10. The in-vivo use of superparamagnetic iron oxide nanoparticles to detect inflammation elicits a cytokine response but does not aggravate experimental arthritis

    NARCIS (Netherlands)

    Vermeij, E.A.; Koenders, M.I.; Bennink, M.B.; Crowe, L.A.; Maurizi, L.; Vallee, J.P.; Hofmann, H.; Berg, W.B. van den; Lent, P.L. van; Loo, F.A. van de

    2015-01-01

    BACKGROUND: Superparamagnetic Iron Oxide Nanoparticles (SPION) are used in diagnostic imaging of a variety of different diseases. For such in-vivo application, an additional coating with a polymer, for example polyvinyl alcohol (PVA), is needed to stabilize the SPION and prevent aggregation. As the

  11. Imaging of liver cancer

    Institute of Scientific and Technical Information of China (English)

    Ben Ariff; Claire R Lloyd; Sameer Khan; Mohamed Shariff; Andrew V Thillainayagam; Devinder S Bansi; Shahid A Khan; Simon D Taylor-Robinson; Adrian KP Lim

    2009-01-01

    Improvements in imaging technology allow exploitation of the dual blood supply of the liver to aid in the identi-fication and characterisation of both malignant and benign liver lesions. Imaging techniques available include contrast enhanced ultrasound, computed tomography and magnetic resonance imaging. This review discusses the application of several imaging techniques in the diagnosis and staging of both hepatocellular carcinoma and cholangiocarcinoma and outlines certain characteristics of benign liver lesions. The advantages of each imaging technique are highlighted, while underscoring the potential pitfalls and limitations of each imaging modality.

  12. [Cysts of the liver

    DEFF Research Database (Denmark)

    Hillingso, J.G.; Kirkegaard, P.

    2008-01-01

    Cysts of the liver are discovered in connection with a scope of diseases ranging from simple, infectious, or parasitic to neoplastic cysts. Symptoms, paraclinical, radiological and diagnostic characteristics are described with emphasis on ruling out malignancy. The treatment options from ultrasound...... guided drainage to resections and liver transplantation are discussed. It is concluded that up to 25% of cysts must be treated surgically, because recurrence after percutaneous or laparoscopic treatment is between 5% and 71%, and only resection or liver transplantation are curative Udgivelsesdato: 2008/4/14...

  13. Liver-targeting macromolecular MRI contrast agents

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Macromolecular ligands with liver-targeting group (pyridoxamine, PM) PHEA-DTPA-PM and PAEA-DTPA-PM were prepared by the incorporation of different amount of diethylenetriaminepentaacetic acid monopyridoxamine group (DTPA-PM) into poly-a, b-[N-(2-hydroxyethyl)-L- aspartamide] (PHEA) and poly-a, b-[N-(2-aminoethyl)-L-aspartamide] (PAEA). The macromolecular ligands thus obtained were further complexed with gadolinium chloride to give macromolecular MRI contrast agents with different Gd(Ⅲ) contents. These macromolecular ligands and their gadolinium complexes were characterized by 1H NMR, IR, UV and elementary analysis. Relaxivity studies showed that these polyaspartamide gadolinium complexes possess higher relaxation effectiveness than that of the clinically used Gd-DTPA. Magnetic resonance imaging of the liver in rats and experimental data of biodistribution in mice indicate that these macromolecular MRI contrast agents containing pyridoxamine exhibit liver-targeting property.

  14. The expression of IFN-gamma and its receptor in the liver of experimental biliatry atresia%小鼠胆道闭锁肝脏组织干扰素-γ及其受体mRNA表达

    Institute of Scientific and Technical Information of China (English)

    汤绍涛; 马亚贞; 杨瑛

    2008-01-01

    Objective To study the expression pattern of IFN-γ and IFN-γ receptor in the liver of biliary atresia(BA)mice.Methods Biliary atresia were induced in mice by intra-peritoneal RRV injection.Forty-five mice were of BA group and 24 mice which received 2%FCS-MEM intraperitoneal-ly were used as control The expression of IFN-γ7 and IFN-γ mRNA in livers of mice were detected with RT-PER.Results Compared to the control group,the expression of IFN-γ in the liver of BA mice at different ages was much higher,It increased first and then deereased,peaking on the 9th days after inoculating with RRv.The level was aboUt thirty times that of the control group.Meanwhile the IFN-γ R mRNA expression also increased first and then decreased,and it peaked on the 9th day.It was significantly higher than control group on the 3,6,9,14th day.The level dropped back to that of the control on the 21th day.Conclusions The expression of IFN-γ and its receptor increased almost synchronously in the livers of BA mice,a possible explanation could be receptor specific effects of in-terferon-γ on the signal transduction levels.%目的 动态检测小鼠胆道闭锁(biliary atresia,BA)模型肝脏组织中干扰素-γ(IFN-γ)及其受体IFN-γ R mRNA的表达情况,探索其与BA发生的关系.方法 采用腹腔注射恒河猴轮状病毒建立BALB/c新生小鼠BA模型,其巾BA组45只,对照组24只(腹腔注射病毒培养液).应用RT-PCR方法检测小鼠模型肝脏中IFN-γ及其受体mRNA的表达.结果 与对照组小鼠相比,不同鼠龄BA组肝内IFN-γ mRNA的表达水平均明显高于对照组,并出现先升高后降低趋势,第九天时达到峰值,约为对照组30倍.IFN-γ受体mRNA表达水平同样出现先升高后下降趋势,第九天达到最高水平,明显高于对照组.IFN-γ受体mRNA在第3、6、9、14天时明显高于对照组,到第21天时恢复到基线水平.结论 小鼠BA模型肝组织中IFN-γ及其受体mRNA表达水平基本同步上调,IFN-γ通

  15. 活体猪肝分次多部位多模式射频消融的实验观察%Experimental study of radiofrequency ablation of liver in swine

    Institute of Scientific and Technical Information of China (English)

    张秀梅; 汪欣; 万远廉; 陈国卫; 李荣杰; 陈敏华

    2013-01-01

    目的 探讨肝脏分次多部位经皮及开腹射频消融策略实施的可行性及疗效.方法 活体家猪1只,先后3次(间隔5d)行超声引导下经皮及开腹肝脏射频消融,共产生6个消融灶,经皮超声、超声造影、开腹术中超声、增强CT等影像学方法观察射频消融对胆系、腹壁、肝静脉及门静脉等结构变化及射频消融疗效.结果 肝门部消融灶致邻近肝总管扩张,与之平行布针的消融灶内的肝静脉未见明显实性栓子,2个消融灶未完全相融;被膜下注水后进行射频消融仍可见邻近腹壁小范围灼伤,随时间延长,被膜下充血肝组织发生凝固坏死;术中专用射频电极针末端形成碳化颗粒,出针过程中致针道出血,使用明胶海绵止血效果佳;在能量相同条件下,阻断入肝血流后消融灶明显增大.结论 多种射频消融方式具有较好的可行性和安全性,特殊部位肿瘤消融并发症增加.%Objective To explore the feasibility and efficacy of multiple-radiofrequency ablation (RFA) in swine liver.Methods One swine undergone percutaneous and intra-operative RFA for three times in succession (an interval of 5 days) guided by real-time ultrasound.Then 6 ablated lesions formed.The outcome of RFA and the change of tissues adjacent to ablated lesions (billiary,liver vascular and abdominal wall) were observed by trans-abdominal ultrasonography (US),contrast enhanced ultrasound (CEUS),intra-operative ultrasound (IOUS) and contrast enhanced computed tomography (CT).Results Bile duct dilatation was found beside primary porta hepatis on US,CT,IOUS after RFA.There was no thrombus in liver vein through the ablated lesion with electrodes parallel to primary porta hepatis.Two ablated lesions were incompletely fused together.Small thermal injury was observed on abdominal wall after an injection of saline into subcapsular gap.Subcapsular hepatic tissue around ablation lesion changed into coagulative necrosis from

  16. Mice with humanized liver endothelium

    NARCIS (Netherlands)

    el Filali, E.

    2014-01-01

    The only curative treatment option for a large proportion of patients suffering from a liver disorder is liver transplantation. The use of ex vivo genetically modified autologous liver cells instead of whole liver transplantation could overcome the problem of donor scarcity. Even though clinical tri

  17. Dysregulation of iron and copper homeostasis innonalcoholic fatty liver

    Institute of Scientific and Technical Information of China (English)

    Elmar Aigner; Günter Weiss; Christian Datz

    2015-01-01

    Elevated iron stores as indicated by hyperferritinemiawith normal or mildly elevated transferrin saturationand mostly mild hepatic iron deposition are acharacteristic finding in subjects with non-alcoholicfatty liver disease (NAFLD). Excess iron is observedin approximately one third of NAFLD patients andis commonly referred to as the "dysmetabolic ironoverload syndrome". Clinical evidence suggests thatelevated body iron stores aggravate the clinical courseof NAFLD with regard to liver-related and extrahepaticdisease complications which relates to the fact thatexcess iron catalyses the formation of toxic hydroxylradicalssubsequently resulting in cellular damage. Ironremoval improves insulin sensitivity, delays the onsetof type 2 diabetes mellitus, improves pathologic liverfunction tests and likewise ameliorates NAFLD histology.Several mechanisms contribute to pathologic ironaccumulation in NAFLD. These include impaired ironexport from hepatocytes and mesenchymal Kupffer cellsas a consequence of imbalances in the concentrationsof iron regulatory factors, such as hepcidin, cytokines,copper or other dietary factors. This review summarizesthe knowledge about iron homeostasis in NAFLD andthe rationale for its therapeutic implications.

  18. Autoimmune liver diseases

    Institute of Scientific and Technical Information of China (English)

    Pietro Invernizzi; Ian R Mackay

    2008-01-01

    The liver was one of the earliest recognized sites among autoimmune diseases yet autoimmune hepatitis,primary biliary cirrhosis,primary sclerosing cholangitis,and their overlap forms,are still problematic in diagnosis and causation.The contributions herein comprise 'pairs of articles' on clinical characteristics,and concepts of etiopathogenesis,for each of the above diseases,together with childhood autoimmune liver disease,overlaps,interpretations of diagnostic serology,and liver transplantation.This issue is timely,since we are witnessing an ever increasing applicability of immunology to a wide variety of chronic diseases,hepatic and non-hepatic,in both developed and developing countries.The 11 invited expert review articles capture the changing features over recent years of the autoimmune liver diseases,the underlying immunomolecular mechanisms of development,the potent albeit still unexplained genetic influences,the expanding repertoire of immunoserological diagnostic markers,and the increasingly effective therapeutic possibilities.

  19. Pediatric liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Marco Spada; Silvia Riva; Giuseppe Maggiore; Davide Cintorino; Bruno Gridelli

    2009-01-01

    In previous decades, pediatric liver transplantation has become a state-of-the-art operation with excellent success and limited mortality. Graft and patient survival have continued to improve as a result of improvements in medical, surgical and anesthetic management, organ availability, immunosuppression, and identification and treatment of postoperative complications. The utilization of split-liver grafts and living-related donors has provided more organs for pediatric patients. Newer immunosuppression regimens, including induction therapy, have had a significant impact on graft and patient survival. Future developments of pediatric liver transplantation will deal with long-term followup, with prevention of immunosuppression-related complications and promotion of as normal growth as possible. This review describes the state-of-the-art in pediatric liver transplantation.

  20. [Wilson disease: liver form].

    Science.gov (United States)

    Guerra Montero, Luis; Ortega Álvarez, Félix; Sumire Umeres, Julia; Cok García, Jaime

    2015-01-01

    Wilson disease (WD) is a disorder of copper metabolism that is inherited as an autosomal recessive, which produces toxic copper accumulation mainly in the liver and brain, in general has two ways presentation, liver at early ages and neurological in later ages. We present the case of a female patient of 21 years diagnosed of WD in liver cirrhosis that started with an edematous ascites without any neurological symptoms despite the age. Their laboratory studies showed decrease in serum ceruloplasmin and high cupruria within 24 hours of the disease , characteristic data of WD. Although WD is not a common disease should be suspected in all chronic liver disease of unknown etiology with negative viral markers and autoimmunity with or without neurological manifestations as soon as posible and starting treatment with copper chelating mainly leads to a substantial improvement the prognosis of these patients.

  1. Liver Transplant: Nutrition

    Science.gov (United States)

    ... include poultry, eggs, fish, tofu, and soy protein. Low Sodium -- Symptoms of advanced liver disease include excess fluid ... it is very important to stick to a low sodium diet, especially when these symptoms start to develop. ...

  2. [Nutrition and liver failure].

    Science.gov (United States)

    Plauth, M

    2013-06-01

    In the critically ill liver patient, nutrition support is not very different from that given for other illnesses. In hyperacute liver failure, nutrition support is of less importance than in the other subtypes of acute liver failure that take a more protracted course. Nasoenteral tube feeding using a polymeric standard formula should be the first-line approach, while parenteral nutrition giving glucose, fat, amino acids, vitamins, and trace elements is initiated when enteral nutrition is insufficient or impracticable. In chronic liver disease, notably cirrhosis, there is frequently protein malnutrition indicating a poor prognosis and requiring immediate initiation of nutrition support. Enteral nutrition ensuring an adequate provision of energy and protein should be preferred. Particular care should be taken to avoid refeeding syndrome and to treat vitamin and trace element deficiency.

  3. Role of lipid rafts in liver health and disease

    Institute of Scientific and Technical Information of China (English)

    Angela Dolganiuc

    2011-01-01

    Liver diseases are an increasingly common cause of morbidity and mortality; new approaches for investigation of mechanisms of liver diseases and identification of therapeutic targets are emergent. Lipid rafts (LRs) are specialized domains of cellular membranes that are enriched in saturated lipids; they are small, mobile, and are key components of cellular architecture, protein partition to cellular membranes, and signaling events. LRs have been identified in the membranes of all liver cells, parenchymal and non-parenchymal; more importantly, LRs are active participants in multiple physiological and pathological conditions in individual types of liver cells. This article aims to review experimental-based evidence with regard to LRs in the liver, from the perspective of the liver as a whole organ composed of a multitude of cell types. We have gathered up-to-date information related to the role of LRs in individual types of liver cells, in liver health and diseases, and identified the possibilities of LR-dependent therapeutic targets in liver diseases.

  4. Acute liver failure

    DEFF Research Database (Denmark)

    Larsen, Fin Stolze; Bjerring, Peter Nissen

    2011-01-01

    Acute liver failure (ALF) results in a multitude of serious complications that often lead to multi-organ failure. This brief review focuses on the pathophysiological processes in ALF and how to manage these.......Acute liver failure (ALF) results in a multitude of serious complications that often lead to multi-organ failure. This brief review focuses on the pathophysiological processes in ALF and how to manage these....

  5. Liver and Biliary System

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008546 Effects of gene-transfected bone marrow-derived liver stem cell transplantation on accumulation of extracellular matrix in rats with liver fibrosis.SUN Chao(孙超),et al.Dept Gastroenterol,Xinhua Hosp,Shanghai Jiaotong Univ,Shanghai 200092.Natl Med J China 2008;88(38):2685-2689. Objective To explore the effects of urokinase-type plasminogen activator(uPA)gene modified bone marrow-derived stem cell(BDLSC)

  6. Fatty liver in children

    OpenAIRE

    Rafeey, Mandana; Mogaddasi,; Hasani, Alka; Ghaffari, Shamsi

    2009-01-01

    Mandana Rafeey1, Fakhrossadat Mortazavi2, Nafiseh Mogaddasi2, Ghergherehchi Robabeh2, Shamsi Ghaffari2, Alka Hasani31Liver and gastrointestinal Research Center; 2Tabriz University (Medical Science) Tabriz, Iran; 3Research Center of Infectious Diseases and Tropical MedicineAims: The aim of this study is to investigate the clinical and laboratory characteristics of nonalcoholic fatty liver disease (NAFLD) in a referral center of pediatrics in the northwest of Iran.Methods: In this cross-section...

  7. Immunological response in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The development of alcoholic liver disease (ALD) can be attributed to many factors that cause damage to the liver and alter its functions. Data collected over the last 30 years strongly suggests that an immune component may be involved in the onset of this disease. This is best evidenced by the detection of circulating autoantibodies,infiltration of immune cells in the liver, and the detection of hepatic aldehyde modified proteins in patients with ALD. Experimentally, there are numerous immune responses that occur when proteins are modified with the metabolites of ethanol. These products are formed in response to the high oxidative state of the liver during ethanol metabolism, causing the release of many inflammatory processes and potential of necrosis or apoptosis of liver cells. Should cellular proteins become modified with these reactive alcohol metabolites and be recognized by the immune system, then immune responses may be initiated. Therefore, it was the purpose of this article to shed some insight into how the immune system is involved in the development and/or progression of ALD.

  8. Liver disease and malnutrition.

    Science.gov (United States)

    Purnak, Tugrul; Yilmaz, Yusuf

    2013-08-01

    Patients with hepatic disorders are exceptionally vulnerable to developing malnutrition because of the key role played by the liver in regulating the nutritional state and the energy balance. Moreover, the presence of chronic liver disorders could reduce the appetite and thus influence the nutrient intake. Poor nutritional status has been shown in various patient groups with hepatic disorders, and particularly in patients with alcoholic cirrhosis who are at high nutritional risk. It is well established that malnourished patients with liver diseases generally have a higher risk of developing adverse clinical outcomes and increased healthcare costs. Nutrition screening with the Subjective Global Assessment and anthropometric measurements are an important first step in the early identification of malnutrition and initiates the whole nutrition care process. It is therefore important for appropriate nutrition policies and protocols to be implemented so that all patients with chronic liver diseases are monitored closely from a nutritional standpoint. Early and evidence-based nutritional interventions are eagerly needed to minimize the nutritional decline associated with chronic liver disorders and ultimately improve the prognosis of such patients. This review includes a comprehensive analysis of methods to identify malnutrition in patients with chronic liver diseases as well as the extent and impact of the malnutrition problem in selected patient populations.

  9. Split liver transplantation.

    Science.gov (United States)

    Yersiz, H; Cameron, A M; Carmody, I; Zimmerman, M A; Kelly, B S; Ghobrial, R M; Farmer, D G; Busuttil, R W

    2006-03-01

    Seventy-five thousand Americans develop organ failure each year. Fifteen percent of those on the list for transplantation die while waiting. Several possible mechanisms to expand the organ pool are being pursued including the use of extended criteria donors, living donation, and split deceased donor transplants. Cadaveric organ splitting results from improved understanding of the surgical anatomy of the liver derived from Couinaud. Early efforts focused on reduced-liver transplantation (RLT) reported by both Bismuth and Broelsch in the mid-1980s. These techniques were soon modified to create both a left lateral segment graft appropriate for a pediatric recipient and a right trisegment for an appropriately sized adult. Techniques of split liver transplantation (SLT) were also modified to create living donor liver transplantation. Pichlmayr and Bismuth reported successful split liver transplantation in 1989 and Emond reported a larger series of nine split procedures in 1990. Broelsch and Busuttil described a technical modification in which the split was performed in situ at the donor institution with surgical division completed in the heart beating cadaveric donor. In situ splitting reduces cold ischemia, simplifies identification of biliary and vascular structures, and reduces reperfusion hemorrhage. However, in situ splits require specialized skills, prolonged operating room time, and increased logistical coordination at the donor institution. At UCLA over 120 in situ splits have been performed and this technique is the default when an optimal donor is available. Split liver transplantation now accounts for 10% of adult transplantations at UCLA and 40% of pediatric transplantations.

  10. Gut microbiota and host metabolism in liver cirrhosis.

    Science.gov (United States)

    Usami, Makoto; Miyoshi, Makoto; Yamashita, Hayato

    2015-11-07

    The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulating the activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probiotics-treated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics

  11. An experimental study on the effect of capsaicin on hepatic stellate cells and liver fibrogenesis%辣椒素调节肝星状细胞活性延缓肝纤维化的实验研究

    Institute of Scientific and Technical Information of China (English)

    俞富祥; 吴志伟; 朱千东; 符竣惠; 张启瑜

    2014-01-01

    目的 探讨辣椒素对大鼠肝星状细胞(hepatic stellate cells,HSCs)活性的影响及其对活体肝纤维化的治疗作用.方法 DCFH-DA法检测辣椒素对HSCs中活性氧的影响;用酶标法检测辣椒素对HSCs增殖的影响;Western blot检测HSCs α-肌动蛋白(α-SMA)的表达;RT-PCR检测辣椒素对HSCs纤维化相关基因表达的影响;流式细胞仪检测辣椒素对HSCs凋亡的影响;Western blot法检测bcl-2、bax、细胞色素酶c(cytochrome,cyt-c)等蛋白的表达;建立鼠肝纤维化模型,经腹腔输注辣椒素,检测肝组织病理切片,肝纤维化指标.结果 辣椒素抑制HSCs中活性氧的产生,抑制HSCs的活化(F=57.392,P<0.05)与增殖(F=13.267,P<0.05),促进HSCs的凋亡(F=235.571,P<0.05),促进凋亡相关蛋白Bax、cyt-c、caspase-3的表达(分别F=29.334,38.274,138.329,均P<0.05).改变HSCs纤维化相关基因TGF-β1、TIMP-1的表达(分别F=376.534,253.751,均P<0.05),活体实验显示辣椒素可降低肝羟脯氨酸含量及血清Ⅲ型胶原和透明质酸水平(分别F=153.397,27.149,38.392,均P<0.05).结论 辣椒素抑制HSCs增殖活化并诱导其凋亡.辣椒素对肝纤维化具有一定的抑制作用.%Objective To investigate the effect of capsaicin on hepatic stellate cells (HSCs) and liver fibrogenesis.Methods HSCs were cultured.The reactive oxygen in HSCs under capsaicin at different concentrations was tested by DCFH-DA kit.The proliferation of HSCs was detected by CCK-8 test kit.Smoothmuscle α-actin (α-SMA) expression of HSCs was evaluated by Western blot.The fibrosisrelated genes were tested by RT-PCR.The apoptosis of HSCs was measured by flow cytometer.Bcl-2,bax and cyt-c was detected by Western blot.A murine model of liver fibrogenes was established.Capsaicin of different concentration was injected intraperitoneally.Liver pathology was observed using HE staining.Hydroxyproline content of liver and levels of collagen Ⅲ and hyaluronic acid in serum were

  12. Adult-to-adult living donor liver transplantation for acute liver failure in China

    Institute of Scientific and Technical Information of China (English)

    Ding Yuan; Fei Liu; Yong-Gang Wei; Bo Li; Lv-Nan Yan; Tian-Fu Wen; Ji-Chun Zhao

    2012-01-01

    AIM:To investigate the long-term outcome of recipients and donors of adult-to-adult living-donor liver transplantation (AALDLT) for acute liver failure (ALF).METHODS:Between January 2005 and March 2010,170 living donor liver transplantations were performed at West China Hospital of Sichuan University.All living liver donor was voluntary and provided informed consent.Twenty ALF patients underwent AALDLT for rapid deterioration of liver function.ALF was defined based on the criteria of the American Association for the Study of Liver Diseases,including evidence of coagulation abnormality [international normalized ratio (INR) ≥ 1.5] and degree of mental alteration without pre-existing cirrhosis and with an illness of < 26 wk duration.We reviewed the clinical indications,operative procedure and prognosis of AALDTL performed on patients with ALF and corresponding living donors.The potential factors of recipient with ALF and corresponding donor outcome were respectively investigated using multivariate analysis.Survival rates after operation were analyzed using the Kaplan-Meier method.Receiver operator characteristic (ROC) curve analysis was undertaken to identify the threshold of potential risk factors.RESULTS:The causes of ALF were hepatitis B (n =18),drug-induced (n =1) and indeterminate (n =1).The score of the model for end-stage liver disease was 37.1 ± 8.6,and the waiting duration of recipients was 5 ± 4 d.The graft types included right lobe (n=17) and dual graft (n =3).The mean graft weight was 623.3 ± 111.3 g,which corresponded to graft-to-recipient weight ratio of 0.95% ± 0.14%.The segment Ⅴor Ⅷ hepatic vein was reconstructed in 11 right-lobe grafts.The 1-year and 3-year recipient's survival and graft survival rates were 65% (13 of 20).Postoperative results of total bilirubin,INR and creatinine showed obvious improvements in the survived patients.However,the creatinine level of the deaths was increased postoperatively and became more aggravated

  13. Excellent survival after liver transplantation for isolated polycystic liver disease : an European Liver Transplant Registry study

    NARCIS (Netherlands)

    van Keimpema, Loes; Nevens, Frederik; Adam, Rene; Porte, Robert J.; Fikatas, Panagiotis; Becker, Thomas; Kirkegaard, Preben; Metselaar, Herold J.; Drenth, Joost P. H.

    2011-01-01

    Patients with end-stage isolated polycystic liver disease (PCLD) suffer from incapacitating symptoms because of very large liver volumes. Liver transplantation (LT) is the only curative option. This study assesses the feasibility of LT in PCLD. We used the European Liver Transplant Registry (ELTR) d

  14. Excellent survival after liver transplantation for isolated polycystic liver disease: an European Liver Transplant Registry study

    DEFF Research Database (Denmark)

    van Keimpema, Loes; Nevens, Frederik; Adam, René

    2011-01-01

    Patients with end-stage isolated polycystic liver disease (PCLD) suffer from incapacitating symptoms because of very large liver volumes. Liver transplantation (LT) is the only curative option. This study assesses the feasibility of LT in PCLD. We used the European Liver Transplant Registry (ELTR...

  15. Experimental and clinical study of the role of Wnt induced secreted protein-1 in liver fibrosis%Wnt诱导分泌蛋白-1介导肝纤维化发生的实验及临床观察

    Institute of Scientific and Technical Information of China (English)

    李玮; 熊伍军; 简易成; 江鸣; 何益; 刘雁冰

    2011-01-01

    目的 探讨Wnt诱导分泌蛋白-1(WISP-1)在大鼠肝纤维化模型表达水平变化及其与慢性肝病患者病程进展的相关性.方法 四氯化碳CCl4皮下注射制作大鼠肝纤维化动物模型,取正常组、造模8周组、造模12周组大鼠肝组织,利用免疫组化观察大鼠肝组织WISP-1表达水平的变化,光镜下半定量分析;收集健康体检者血清20例,慢性HBV携带者患者血清20例,乙型肝炎肝硬化患者血清60例,利用ELISA测定血清WISP-1水平变化,利用放射免疫检测血清透明质酸(HA)、层粘蛋白(LN)、前Ⅲ型胶原(PⅢP)、Ⅳ型胶原(CⅣ)水平,分析WISP-1水平与血清肝纤维化指标的相关性.结果 造模8、12周组WISP-1表达水平分别为11.0±2.4、23.8±4.8,与正常组2.3±2.1比较差异具有统计学意义(P<0.05);慢性HBV携带者、乙型肝炎肝硬化患者血清WISP-1水平分别为(65.5±18.8)、(71.2±18.2)ng/ml,与健康对照组(57.3±15.2)ng/ml比较差异具有统计学意义(P<0.05),相关分析表明WISP-1与HA、LN、PⅢP、CⅣ相关系数分别为0.41、0.53、0.50、0.64(P<0.05).结论 WISP-1参与实验性肝纤维化的发生,血清WISP-1水平与慢性肝病病程进展相关,WISP-1在肝纤维化、肝硬化的作用及机制值得进一步研究.%Objective To clarify the expression change of Wnt-induced secreted protein-I (WISP-1) in experimental liver fibrosis in rats and to determine whether it is correlated with the progress of human chronic liver diseases. Methods Experimental liver fibrosis was induced in male Sprague-Dawley rats with CCl4. At the end of the 8 wk, 12wk animals were sacrificed, liver tissue were collected respectively for pathological examination and immunohistochemistry. Serums were collected from 20 individuals, 20 chronic hepatitis B patients and 60 liver cirrhosis patients. The serum levels of WISP-1 were examined with ELISA. HA, LN, P Ⅲ P and C Ⅳ were examined with radioimmunology assay. Analysis of the

  16. Cell therapy for liver diseases: current medicine and future promises.

    Science.gov (United States)

    Alejandra, Meza-Ríos; Juan, Armendáriz-Borunda; Ana, Sandoval-Rodríguez

    2015-06-01

    Liver diseases are a major health problem worldwide since they usually represent the main causes of death in most countries, causing excessive costs to public health systems. Nowadays, there are no efficient current therapies for most hepatic diseases and liver transplant is infrequent due to the availability of organs, cost and risk of transplant rejection. Therefore, alternative therapies for liver diseases have been developed, including cell-based therapies. Stem cells (SCs) are characterized by their self-renewing capacity, unlimited proliferation and differentiation under certain conditions into tissue- or organ-specific cells with special functions. Cell-based therapies for liver diseases have been successful in experimental models, showing anti-inflammatory, antifibrogenic and regenerative effects. Nowadays, clinical trials using SCs for liver pathologies are increasing in number, and those that have reached publication have achieved favorable effects, encouraging us to think that SCs will have a potential clinical use in a short time.

  17. Glucocerebrosidase deficiency accelerates the accumulation of proteinase K-resistant α-synuclein and aggravates neurodegeneration in a Drosophila model of Parkinson's disease.

    Science.gov (United States)

    Suzuki, Mari; Fujikake, Nobuhiro; Takeuchi, Toshihide; Kohyama-Koganeya, Ayako; Nakajima, Kazuki; Hirabayashi, Yoshio; Wada, Keiji; Nagai, Yoshitaka

    2015-12-01

    Alpha-synuclein (αSyn) plays a central role in the pathogenesis of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Recent multicenter genetic studies have revealed that mutations in the glucocerebrosidase 1 (GBA1) gene, which are responsible for Gaucher's disease, are strong risk factors for PD and DLB. However, the mechanistic link between the functional loss of glucocerebrosidase (GCase) and the toxicity of αSyn in vivo is not fully understood. In this study, we employed Drosophila models to examine the effect of GCase deficiency on the neurotoxicity of αSyn and its molecular mechanism. Behavioral and histological analyses showed that knockdown of the Drosophila homolog of GBA1 (dGBA1) exacerbates the locomotor dysfunction, loss of dopaminergic neurons and retinal degeneration of αSyn-expressing flies. This phenotypic aggravation was associated with the accumulation of proteinase K (PK)-resistant αSyn, rather than with changes in the total amount of αSyn, raising the possibility that glucosylceramide (GlcCer), a substrate of GCase, accelerates the misfolding of αSyn. Indeed, in vitro experiments revealed that GlcCer directly promotes the conversion of recombinant αSyn into the PK-resistant form, representing a toxic conformational change. Similar to dGBA1 knockdown, knockdown of the Drosophila homolog of β-galactosidase (β-Gal) also aggravated locomotor dysfunction of the αSyn flies, and its substrate GM1 ganglioside accelerated the formation of PK-resistant αSyn. Our findings suggest that the functional loss of GCase or β-Gal promotes the toxic conversion of αSyn via aberrant interactions between αSyn and their substrate glycolipids, leading to the aggravation of αSyn-mediated neurodegeneration.

  18. Liver transplantation for polycystic liver and massive hepatomegaly

    Institute of Scientific and Technical Information of China (English)

    Salvatore; Gruttadauria; Fabrizio; di; Francesco; Bruno; Gridelli

    2010-01-01

    Liver tumor and other benign liver diseases such as polycystic liver disease can cause massive hepatomegaly and may represent an indication for liver transplantation(LT)in some instances.In this setting,LT can be extremely difficult and challenging due to its decreased mobility and access to vascular supply.Benefit from either a right or a left partial liver resection during the transplant procedure has been advocated to safely accomplish the hepatectomy of the native liver.Although we believe that partial ...

  19. Th2-Associated Alternative Kupffer Cell Activation Promotes Liver Fibrosis without Inducing Local Inflammation

    Science.gov (United States)

    López-Navarrete, Giuliana; Ramos-Martínez, Espiridión; Suárez-Álvarez, Karina; Aguirre-García, Jesús; Ledezma-Soto, Yadira; León-Cabrera, Sonia; Gudiño-Zayas, Marco; Guzmán, Carolina; Gutiérrez-Reyes, Gabriela; Hernández-Ruíz, Joselín; Camacho-Arroyo, Ignacio; Robles-Díaz, Guillermo; Kershenobich, David; Terrazas, Luis I.; Escobedo, Galileo

    2011-01-01

    Cirrhosis is the final outcome of liver fibrosis. Kupffer cell-mediated hepatic inflammation is considered to aggravate liver injury and fibrosis. Alternatively-activated macrophages are able to control chronic inflammatory events and trigger wound healing processes. Nevertheless, the role of alternative Kupffer cell activation in liver harm is largely unclear. Thus, we evaluated the participation of alternatively-activated Kupffer cells during liver inflammation and fibrosis in the murine model of carbon tetrachloride-induced hepatic damage. To stimulate alternative activation in Kupffer cells, 20 Taenia crassiceps (Tc) larvae were inoculated into BALBc/AnN female mice. Six weeks post-inoculation, carbon tetrachloride or olive oil were orally administered to Tc-inoculated and non-inoculated mice twice per week during other six weeks. The initial exposure of animals to T. crassiceps resulted in high serum concentrations of IL-4 accompanied by a significant increase in the hepatic mRNA levels of Ym-1, with no alteration in iNOS expression. In response to carbon tetrachloride, recruitment of inflammatory cell populations into the hepatic parenchyma was 5-fold higher in non-inoculated animals than Tc-inoculated mice. In contrast, carbon tetrachloride-induced liver fibrosis was significantly less in non-inoculated animals than in the Tc-inoculated group. The latter showed elevated IL-4 serum levels and low IFN-γ concentrations during the whole experiment, associated with hepatic expression of IL-4, TGF-β, desmin and α-sma, as well as increased mRNA levels of Arg-1, Ym-1, FIZZ-1 and MMR in Kupffer cells. These results suggest that alternative Kupffer cell activation is favored in a Th2 microenvironment, whereby such liver resident macrophages could exhibit a dichotomic role during chronic hepatic damage, being involved in attenuation of the inflammatory response but at the same time exacerbation of liver fibrosis. PMID:22110380

  20. Th2-Associated Alternative Kupffer Cell Activation Promotes Liver Fibrosis without Inducing Local Inflammation

    Directory of Open Access Journals (Sweden)

    Giuliana López-Navarrete, Espiridión Ramos-Martínez, Karina Suárez-Álvarez, Jesús Aguirre-García, Yadira Ledezma-Soto, Sonia León-Cabrera, Marco Gudiño-Zayas, Carolina Guzmán, Gabriela Gutiérrez-Reyes

    2011-01-01

    Full Text Available Cirrhosis is the final outcome of liver fibrosis. Kupffer cell-mediated hepatic inflammation is considered to aggravate liver injury and fibrosis. Alternatively-activated macrophages are able to control chronic inflammatory events and trigger wound healing processes. Nevertheless, the role of alternative Kupffer cell activation in liver harm is largely unclear. Thus, we evaluated the participation of alternatively-activated Kupffer cells during liver inflammation and fibrosis in the murine model of carbon tetrachloride-induced hepatic damage. To stimulate alternative activation in Kupffer cells, 20 Taenia crassiceps (Tc larvae were inoculated into BALBc/AnN female mice. Six weeks post-inoculation, carbon tetrachloride or olive oil were orally administered to Tc-inoculated and non-inoculated mice twice per week during other six weeks. The initial exposure of animals to T. crassiceps resulted in high serum concentrations of IL-4 accompanied by a significant increase in the hepatic mRNA levels of Ym-1, with no alteration in iNOS expression. In response to carbon tetrachloride, recruitment of inflammatory cell populations into the hepatic parenchyma was 5-fold higher in non-inoculated animals than Tc-inoculated mice. In contrast, carbon tetrachloride-induced liver fibrosis was significantly less in non-inoculated animals than in the Tc-inoculated group. The latter showed elevated IL-4 serum levels and low IFN-γ concentrations during the whole experiment, associated with hepatic expression of IL-4, TGF-β, desmin and α-sma, as well as increased mRNA levels of Arg-1, Ym-1, FIZZ-1 and MMR in Kupffer cells. These results suggest that alternative Kupffer cell activation is favored in a Th2 microenvironment, whereby such liver resident macrophages could exhibit a dichotomic role during chronic hepatic damage, being involved in attenuation of the inflammatory response but at the same time exacerbation of liver fibrosis.

  1. Tamarind seed extract mitigates the liver oxidative stress in arthritic rats.

    Science.gov (United States)

    Sundaram, Mahalingam Shanmuga; Hemshekhar, Mahadevappa; Thushara, Ram M; Santhosh, Martin Sebastin; Kumar, Somanathapura K Naveen; Paul, Manoj; Devaraja, Sannaningaiah; Kemparaju, Kempaiah; Rangappa, Kanchugarakoppal S; Girish, Kesturu S

    2014-03-01

    Although arthritis is primarily a joint disorder that mainly targets the articular cartilage and subchondral bone, several recent investigations have reported oxidative burst and vital organ damage that are being considered as secondary complications of arthritis. The continuous generation of free radicals like reactive oxygen and nitrogen species is considered as a key culprit in the initiation and propagation of oxidative damage. In addition, activation of T and B cells, macrophages, inflammatory mediators such as TNF-α, IL-1β and IL-6 aggravates the oxidative damage of the vital organs, particularly the liver. The current piece of work demonstrates oxidative stress in the liver of arthritic rats and its amelioration by the procyanidin-rich tamarind seed extract (TSE). The arthritic liver homogenate, mitochondrial and cytosolic fractions were found with increased levels of oxidative stress markers including free radicals. As a consequence, depletion in the levels of glutathione, total thiols, glutathione peroxidase and reductase was evident. Furthermore, the activities of endogenous antioxidant enzymes like superoxide dismutase, catalase and glutathione-S-transferase were found to be significantly altered. The increased and decreased activity of transaminases respectively in serum and liver, along with histological observations, further confirms the liver damage. Unfortunately, the commonly used drugs like NSAIDs and DMARDs have failed to prevent oxidative damage, rather they were found to be the inducers themselves. Interestingly, TSE supplementation was found to significantly inhibit oxidative burst in the liver and maintain homeostasis. Thus, the study clearly demonstrates the protective efficacy of TSE against arthritis-associated oxidative liver damage, including mitochondrial oxidative burst and its associated secondary complications.

  2. Remote ischemic preconditioning protects against liver ischemia-reperfusion injury via heme oxygenase-1-induced autophagy.

    Directory of Open Access Journals (Sweden)

    Yun Wang

    Full Text Available BACKGROUND: Growing evidence has linked autophagy to a protective role of preconditioning in liver ischemia/reperfusion (IR. Heme oxygenase-1 (HO-1 is essential in limiting inflammation and preventing the apoptotic response to IR. We previously demonstrated that HO-1 is up-regulated in liver graft after remote ischemic preconditioning (RIPC. The aim of this study was to confirm that RIPC protects against IR via HO-1-mediated autophagy. METHODS: RIPC was performed with regional ischemia of limbs before liver ischemia, and HO-1 activity was inhibited pre-operation. Autophagy was assessed by the expression of light chain 3-II (LC3-II. The HO-1/extracellular signal-related kinase (ERK/p38/mitogen-activated protein kinase (MAPK pathway was detected in an autophagy model and mineral oil-induced IR in vitro. RESULTS: In liver IR, the expression of LC3-II peaked 12-24 h after IR, and the ultrastructure revealed abundant autophagosomes in hepatocytes after IR. Autophagy was inhibited when HO-1 was inactivated, which we believe resulted in the aggravation of liver IR injury (IRI in vivo. Hemin-induced autophagy also protected rat hepatocytes from IRI in vitro, which was abrogated by HO-1 siRNA. Phosphorylation of p38-MAPK and ERK1/2 was up-regulated in hemin-pretreated liver cells and down-regulated after treatment with HO-1 siRNA. CONCLUSIONS: RIPC may protect the liver from IRI by induction of HO-1/p38-MAPK-dependent autophagy.

  3. Enhanced formation of secondary air pollutants and aggravation of urban smog due to crop residue burning emissions in North India

    Science.gov (United States)

    Sarkar, Chinmoy; Kumar, Vinod; Sinha, Vinayak

    2013-04-01

    Biomass burning causes intense perturbations to regional atmospheric chemistry and air quality and is a significant global source of reactive pollutants to the atmosphere (Andreae and Merlet, 2001). In November 2012, large areas in North India including New Delhi experienced several weeks of aggravated smog and poor air quality due to the impact of crop residue burning, which is a biannual post harvest activity that occurs during Oct-Nov and April-May every year in the agricultural belts of North western India. In-situ high temporal resolution (1 measurement every minute) measurements of a suite of volatile organic compounds measured using proton transfer reaction mass spectrometry (PTR-MS) such as acetonitrile (biomass burning tracer) and aromatic hydrocarbons were performed simultaneously with carbon monoxide, nitrogen oxides, ozone and aerosol mass concentrations (PM 2.5 and PM 10) at a suburban site (30.667°N, 76.729°E and 310 m asl), impacted by air masses that had passed over the burning fields less than 72 hours ago. By using data from the same season but before the post harvest crop residue burning activity had commenced, we were able to quantify enhancements in ambient levels of the measured species due to the crop residue burning activity. When air masses influenced by the fire emissions reached the measurement site, peak values of about 8 ppbV acetonitrile, 4 ppmV CO, 100 ppbV NOx , 30 ppbV toluene and 15 ppbV benzene were observed which represented a factor of 2-5 increase over their ambient levels in the non-fire influenced period. Emission ratios of aromatic hydrocarbons/CO also showed a marked increase. Non fire event (N.F. E.) influenced and fire event (F.E.) influenced air masses had the following emission ratio enhancements: benzene/CO (N.F.E = 3; F.E. = 5), toluene/CO (N.F.E = 4; F.E. = 8.7) and sum of C8 aromatics/CO (N.F.E = 4; F.E. = 7.3) and sum of C9 aromatics/CO (N.F.E = 2.6; F.E. = 3.4). The OH reactivity of air masses which has strong

  4. Gut microbiota and liver diseases.

    Science.gov (United States)

    Minemura, Masami; Shimizu, Yukihiro

    2015-02-14

    Several studies revealed that gut microbiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gut microbiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases.

  5. Hypermagnesemia does not prevent intracranial hypertension and aggravates cerebral hyperperfusion in a rat model of acute hyperammonemia

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Eefsen, Martin; Larsen, Fin Stolze;

    2011-01-01

    Intravenous infusion of magnesium sulfate prevents seizures in patients with eclampsia and brain edema after traumatic brain injury. Neuroprotection is achieved by controlling cerebral blood flow (CBF), intracranial pressure, neuronal glutamate release, and aquaporin-4 (Aqp4) expression....... These factors are also thought to be involved in the development of brain edema in acute liver failure. We wanted to study whether hypermagnesemia prevented development of intracranial hypertension and hyperperfusion in a rat model of portacaval anastomosis (PCA) and acute hyperammonemia. We also studied...... rats receiving ammonia infusion/vehicle and MgSO4) /saline. The effect of MgSO(4) on mean arterial pressure (MAP), intracranial pressure (ICP), CBF, cerebral glutamate and glutamine, and aquaporin-4 expression was studied. Finally, the effect of MgSO4 on MAP, ICP, and CBF was studied, using two...

  6. Silybin and the liver: From basic research to clinical practice

    Institute of Scientific and Technical Information of China (English)

    Carmela Loguercio; Davide Festi

    2011-01-01

    Herbal products are increasingly used, mainly in chronic liver disease. Extracts of milk thistle, Silymarin and silybin, are the most prescribed natural compounds,with different indications, but with no definitive results in terms of clinical efficacy. This review analyzes the available studies on the effects of the purified product silybin, both as a free and a conjugated molecule, on liver cells or on experimentally induced liver damage,and in patients with liver disease. We searched PUBMED for articles pertaining to the in vitro and in vivo effects of silybin, its antifibrotic, anti-inflammatory, and antioxidant properties, as well as its metabolic effects,combined with the authors' own knowledge of the literature. Results indicate that the bioavailability of silybin phytosome is higher than that of silymarin and is less influenced by liver damage; silybin does not show significant interactions with other drugs and at doses < 10 g/d has no significant side effects. Experimental studies have clearly demonstrated the antifibrotic, antioxidant and metabolic effects of silybin; previous human studies were insufficient for confirming the clinical efficacy in chronic liver disease, while ongoing clinical trials are promising. On the basis of literature data, silybin seems a promising drug for chronic liver disease.

  7. The Liver in the Eyes of a Chronobiologist.

    Science.gov (United States)

    Zwighaft, Ziv; Reinke, Hans; Asher, Gad

    2016-04-01

    Our understanding of the molecular underpinnings of the mammalian circadian oscillator and its tight connection to physiology has progressed tremendously during the past decades. The liver is considered the prototypic experimental model tissue for circadian research in peripheral organs. Studies on liver clocks have been highly productive and yielded information about widely different aspects of circadian biology. The liver, as one of the largest organs in the body, has often been used for the identification of core clock and auxiliary clock components, for example, by biochemical purifications. Because the liver is also a major metabolic hub, studies addressing the interplay between circadian clocks and metabolism have been insightful. In addition, the use of liver-specific loss-of-function models for clock components highlighted not only specific physiological roles of the hepatic clock but also its interplay with systemic cues and oscillators in other organs. Recently, technological advances in omics approaches have been successfully applied on the liver, providing a comprehensive depiction of pervasive circadian control of gene expression and protein and metabolite accumulation. In this review, we chose to illuminate specific examples that demonstrate how different experimental approaches--namely, biochemical, metabolic, genetic, and omics methodologies--have advanced our knowledge regarding circadian liver biology and chronobiology in general.

  8. Platelet-activating factor in liver injury: A relational scope

    Institute of Scientific and Technical Information of China (English)

    Nikolaos P Karidis; Gregory Kouraklis; Stamatios E Theocharis

    2006-01-01

    The hepatocyte, the main cellular component of the liver, exhibits variable susceptibility to different types of injury induced by endogenous or exogenous factors.Hepatocellular dysfunction or death and regeneration are dependent upon the complicated interactions between numerous biologically active molecules. Plateletactivating factor (PAF) seems to play a pivotal role as the key mediator of liver injury in the clinical and experimental setting, as implied by the beneficial effects of its receptor antagonists. A comprehensive up-todate overview of the specific functional and regulatory properties of PAF in conditions associated with liver injury is attempted in this review.

  9. Nitric Oxide and Prostaglandins Potentiate the Liver Regeneration Cascade

    Directory of Open Access Journals (Sweden)

    Jodi M Schoen Smith

    2006-01-01

    Full Text Available The liver has the remarkable ability to regenerate following damage or surgical resection. Although this feature of the liver has been studied for over 100 years, the trigger of the liver regeneration cascade remains controversial. Recent experimental evidence supports the hypothesis that nitric oxide (NO and prostaglandins (PGs, released secondary to an increase in the blood flow-to-liver mass ratio following two-thirds partial hepatectomy (PHx, work synergistically to trigger liver regeneration. To extend this research, the hypothesis that NO and PGs are potential therapeutic targets to potentiate the liver regeneration cascade is tested. The NO donor s-nitroso-n-acetylpenicillamine, the phosphodiesterase V antagonist zaprinast (ZAP and PGI2 each potentiated c-fos messenger RNA expression, an index of initiation of the liver regeneration cascade, following PHx. Also, the triple combination of s-nitroso-n-acetylpenicillamine, ZAP and PGI2 potentiated c-fos messenger RNA expression. These results support the hypothesis that NO and PGs can potentiate initiation of the regeneration cascade. An additional index of liver weight restoration 48 h after PHx was also used to test the hypothesis, because this index encompasses the entire liver regeneration cascade. ZAP and 6-keto-PGF1α, a stable metabolite of PGI2, and the combination of ZAP and 6-keto-PGF1α, each potentiated liver weight restoration 48 h after PHx. These results also provide support for the hypothesis that NO and PGs are possible therapeutic targets to potentiate liver regeneration following surgical resection.

  10. Proteasome inhibitor treatment in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    Fawzia Bardag-Gorce

    2011-01-01

    Oxidative stress, generated by chronic ethanol consumption, is a major cause of hepatotoxicity and liver injury. Increased production of oxygen-derived free radicals due to ethanol metabolism by CYP2E1 is principally located in the cytoplasm and in the mitochondria, which does not only injure liver cells, but also other vital organs, such as the heart and the brain. Therefore, there is a need for better treatment to enhance the antioxidant response elements. To date, there is no established treatment to attenuate high levels of oxidative stress in the liver of alcoholic patients. To block this oxidative stress, proteasome inhibitor treatment has been found to significantly enhance the antioxidant response elements of hepatocytes exposed to ethanol. Recent studies have shown in an experimental model of alcoholic liver disease that proteasome inhibitor treatment at low dose has cytoprotective effects against ethanol-induced oxidative stress and liver steatosis. The beneficial effects of proteasome inhibitor treatment against oxidative stress occurred because antioxidant response elements (glutathione peroxidase 2, superoxide dismutase 2, glutathione synthetase, glutathione reductase, and GCLC) were upregulated when rats fed alcohol were treated with a low dose of PS-341 (Bortezomib, Velcade(r)). This is an important finding because proteasome inhibitor treatment up-regulated reactive oxygen species removal and glutathione recycling enzymes, while ethanol feeding alone down-regulated these antioxidant elements. For the first time, it was shown that proteasome inhibition by a highly specific and reversible inhibitor is different from the chronic ethanol feeding-induced proteasome inhibition. As previously shown by our group, chronic ethanol feeding causes a complex dysfunction in the ubiquitin proteasome pathway, which affects the proteasome system, as well as the ubiquitination system. The beneficial effects of proteasome inhibitor treatment in alcoholic liver disease

  11. Stem cells in liver regeneration and their potential clinical applications.

    Science.gov (United States)

    Drosos, Ioannis; Kolios, George

    2013-10-01

    Stem cells constitute a population of "primitive cells" with the ability to divide indefinitely and give rise to specialized cells under special conditions. Because of these two characteristics they have received particular attention in recent decades. These cells are the primarily responsible factors for the regeneration of tissues and organs and for the healing of lesions, a feature that makes them a central key in the development of cell-based medicine, called Regenerative Medicine. The idea of wound and organ repair and body regeneration is as old as the mankind, reflecting the human desire for inhibiting aging and immortality and it is first described in the ancient Greek myth of Prometheus. It is of interest that the myth refers to liver, an organ with remarkable regenerative ability after loss of mass and function caused by liver injury or surgical resection. Over the last decade there has been an important progress in understanding liver physiology and the mechanisms underlying hepatic development and regeneration. As liver transplantation, despite its difficulties, remains the only effective therapy for advanced liver disease so far, scientific interest has nowadays been orientated towards Regenerative Medicine and the use of stem cells to repair damaged liver. This review is focused on the available literature concerning the role of stem cells in liver regeneration. It summarizes the results of studies concerning endogenous liver regeneration and stem cell experimental protocols. Moreover, this review discusses the clinical studies that have been conducted in humans so far.

  12. Liver transplantation in Germany.

    Science.gov (United States)

    Tacke, Frank; Kroy, Daniela C; Barreiros, Ana Paula; Neumann, Ulf P

    2016-08-01

    Liver transplantation (LT) is a well-accepted procedure for end-stage liver disease in Germany. In 2015, 1489 patients were admitted to the waiting list (including 1308 new admissions), with the leading etiologies being fibrosis and cirrhosis (n = 349), alcoholic liver disease (n = 302), and hepatobiliary malignancies (n = 220). Organ allocation in Germany is regulated within the Eurotransplant system based on urgency as expressed by the Model for End-Stage Liver Disease score. In 2015, only 894 LTs (n = 48 from living donors) were performed at 23 German transplant centers, reflecting a shortage of organs. Several factors may contribute to the low number of organ donations. The German transplant legislation only accepts donation after brain death (not cardiac death), whereas advances in neurosurgery and a more frequently requested "palliative care" approach render fewer patients suitable as potential donors. The legislation further requires the active consent of the donor or first-degree relatives before donation. Ongoing debates within the German transplant field address the optimal management of patients with alcoholic liver cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma and measures to increase living donor transplantations. As a result of irregularities at mainly 4 German transplant centers that were exposed in 2012, guiding principles updated by the German authorities have since implemented strict rules (including internal and external auditing, the 8-eyes principle, mandatory repeated testing for alcohol consumption) to prohibit any manipulations in organ allocation. In conclusion, we will summarize important aspects on the management of LT in Germany, discuss legal and organizational aspects, and highlight challenges mainly related to the relative lack of organ donations, increasing numbers of extended criteria donors, and the peculiarities of the recipient patients. Liver Transplantation 22 1136-1142 2016 AASLD.

  13. [Alcoholic liver disease and liver transplantation].

    Science.gov (United States)

    Testino, Gianni; Patussi, Valentino; Scafato, Emanuele

    2013-01-01

    Alcoholic liver disease (ALD) is the second most common diagnosis among patients undergoing liver transplantation (LT) in Europe and in the United States. The outcome of patients transplanted for ALD is at least as good as that for most other diagnoses and better than that for hepatitis C virus. In case of severe acute alcoholic hepatitis (AAH) non-responders to medical therapy, the reason for denying LT is that it requires abstinence from alcohol for six months before consideration for a transplant. A strict application of a period of abstinence as a policy for transplant eligibility is unfair to non-responder patients, as most of them will have died prior to the end of the six-month sober period. In our opinion, in severe AAH subjects with a good social support, with the frequency of self-help groups (alcoholics anonymous or association of clubs of alcoholics in treatment), with the frequency of Alcohol Unit and without severe psychotic or personality disorders, the lack of pre-LT abstinence alone should not be a barrier against being listed.

  14. Carboxylated multi-walled carbon nanotubes aggravated biochemical and subcellular damages in leaves of broad bean (Vicia faba L.) seedlings under combined stress of lead and cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Chengrun, E-mail: chengrunwang@163.com [School of Life Science, Huainan Normal University, Huainan 232001 (China); Liu, Haitao; Chen, Jinyun [School of Life Science, Huainan Normal University, Huainan 232001 (China); Tian, Yuan [Department of Plant, Soil and Microbial Sciences, Michigan State University, East Lansing, MI 48824 (United States); Shi, Jian; Li, Dongdong; Guo, Chen; Ma, Qingping [School of Life Science, Huainan Normal University, Huainan 232001 (China)

    2014-06-01

    Highlights: • MWCNTs-COOH disturb mineral elements and cause oxidative damages in the leaves. • Cd and Pb combination result in reduction of mineral elements and enrichment of Na, involving in toxicity mechanisms. • MWCNTs-COOH facilitate Cd and Pb uptake, and aggravate biochemical and subcellular damages. - Abstract: Increasing industrialization of multi-walled carbon nanotubes (MWCNTs) would inevitably lead to their release into the environment and combination with heavy metals. However, studies concerning the combined effects of MWCNTs and heavy metals on agricultural crops are limited. Herein, effects and mechanisms of carboxylated MWCNTs (MWCNTs-COOH) (2.5, 5 and 10 mg/L) and their combination with 20 μM Pb and 5 μM Cd (shortened as Pb + Cd) on Vicia faba L. seedlings were investigated. The results showed that the MWCNTs-COOH disturbed the imbalance of nutrient elements, and caused oxidative stress and damages in the leaves. Additionally, the combination of MWCNTs-COOH with Pb + Cd resulted in enrichment of Pb and Cd, and deterioration of oxidative damages compared with the treatments of MWCNTs-COOH or Pb + Cd alone in the leaves. As the results, the concentrations of MWCNTs-COOH not only caused oxidative stress, but also exacerbated the biochemical and subcellular damages due to the treatment of Pb + Cd in the leaves. It also suggests that persistent release of MWCNTs-COOH into the environment may cause phytotoxicity and aggravate ecological risks due to combination of heavy metals.

  15. Alcoholic liver disease: The gut microbiome and liver crosstalk

    OpenAIRE

    Hartmann, Phillipp; Seebauer, Caroline T.; Schnabl, Bernd

    2015-01-01

    Alcoholic liver disease is a leading cause of morbidity and mortality worldwide. Alcoholic fatty liver disease can progress to steatohepatitis, alcoholic hepatitis, fibrosis, and cirrhosis. Patients with alcohol abuse show quantitative and qualitative changes in the composition of the intestinal microbiome. Furthermore, patients with alcoholic liver disease have increased intestinal permeability and elevated systemic levels of gut-derived microbial products. Maintaining eubiosis, stabilizing ...

  16. Coupled plasma filtration adsorption in experimental peritonitis-induced septic shock.

    Science.gov (United States)

    Sykora, Roman; Chvojka, Jiri; Krouzecky, Ales; Radej, Jaroslav; Kuncova, Jitka; Varnerova, Veronika; Karvunidis, Thomas; Novak, Ivan; Matejovic, Martin

    2009-05-01

    The coupled plasma filtration adsorption (CPFA) was developed as an adsorptive hemopurification method aimed at nonselective removal of circulating soluble mediators potentially involved in the pathogenesis of sepsis. We hypothesized that this nonselective hemopurification could protect from detrimental consequences of long-term, volume-resuscitated porcine septic shock. In 16 anesthetized, mechanically ventilated, and instrumented pigs, the hyperdynamic septic shock secondary to peritonitis was induced by intraperitoneally inoculating feces and maintained for 22 h with fluid resuscitation and norepinephrine infusion as needed to maintain MAP above 65 mmHg. After 12 h of peritonitis, animals were randomized to receive either supportive treatment (control, n = 8) or CPFA treatment (CPFA, n = 8). Systemic, hepatosplanchnic, and renal hemodynamics; oxygen exchange; energy metabolism (lactate/pyruvate and ketone body ratios); ileal mucosal and renal cortex microcirculation; systemic inflammation (TNF-alpha, IL-6); nitrosative/oxidative stress (thiobarbituric acid reactive species, nitrates + nitrites); and endothelial/coagulation dysfunction (asymmetric dimethylarginine, von Willebrand factor, thrombin-antithrombin complexes, platelet count) were assessed before and 12, 18, and 22 h of peritonitis. Coupled plasma filtration adsorption neither delayed the development of hypotension nor reduced the dose of norepinephrine. The treatment failed to attenuate sepsis-induced alterations in microcirculation, surrogate markers of cellular energetics, endothelial injury, and systemic inflammation. Similarly, CPFA did not protect from lung and liver dysfunction and even aggravated sepsis-induced disturbances in coagulation and oxidative/nitrosative stress. In this porcine model of septic shock, the early treatment with CPFA was not capable of reversing the sepsis-induced disturbances in various biological pathways and organ systems. Both the efficacy and safety of this method

  17. Propylthiouracil for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2005-01-01

    Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease.......Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease....

  18. Propylthiouracil for alcoholic liver disease

    DEFF Research Database (Denmark)

    Fede, Giuseppe; Germani, Giacomo; Gluud, Christian;

    2011-01-01

    Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease.......Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease....

  19. Liver Disease and Pulmonary Hypertension

    Science.gov (United States)

    ... fats, produces several important com- pounds, stores certain vitamins, makes specific amino acids, converts glucose to glycogen, ... liver. This increased pres- sure causes blood to bypass the liver. As a result, the blood is ...

  20. Experimental study of the protective effects of Jiejiu Xiaozhi detection in alcoholic fatty liver rats%解酒消脂汤对酒精性脂肪肝保护作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    梁卫; 梁涛; 张丽玲; 陆瑜; 李子贺; 陈晔; 周斌; 蔡鹰

    2014-01-01

    Objective To observe the effect of Jiejiu Xiaozhi detection on oxidative stress and the expression of cytokine in rats with alcoholic fatty liver ( AFL).Methods Male SD rats were randomly divided into normal group and model group.Rats were administered with alcohol and fed with fat emulsion to replicate AFL model.Model rats were divided in-to the model group , the compound Yiganling group ( 0.04 g · kg -1 ) and three groups of different doses of Jiejiu Xiaozhi detection ( 16.5 ,33.0 , 66.0 g· kg -1 ).In the process of modeling , the normal group and the model group were administered with 0.9%NaCl, and other groups were given corresponding medicine by gavage for 6 weeks, after which the con-tents of malondialdehyde ( MDA) , superoxide dismutase ( SOD) in serum and hepatic tissue , tumor necrosis factor α( TNF-α) and interleukin 1 ( IL-1 ) in serum were examined.The expressing of TNF -αmRNA and IL-1βmRNA in hepatic tissue were detected by RT -PCR.Re-sults Compared with the model group , in the Jiejiu Xiaozhi detection with middle and high doses groups , the contents of MDA in hepatic tissue and serum were significantly reduced ( P <0.05 , P <0.01 ).The ex-pressing of TNF -αmRNA, IL -1βmRNA in hepatic tissue and TNF-α, IL-1 in serum were significantly down -regulated ( P<0.05 , P <0.01 ).The contents of SOD in serum and hepatic tissue were significantly increased ( P<0.05 ,P<0.01 ).Conclusion Jiejiu Xiaozhi detection can reduce inflammatory response in hepatic tissue and decrease lipid peroxidation.So it can protect liver function.%目的:研究解酒消脂汤对酒精性脂肪肝( AFL)大鼠氧化应激及细胞因子的影响。方法将雄性SD大鼠用酒精联合脂肪乳剂法制备AFL大鼠模型。将造模大鼠随机分为模型组、复方益肝灵片组(0.04 g· kg-1)、3个剂量(16.5,33.0,66.0 g· kg-1)解酒消脂汤组。造模同时,正常组和模型组给予0.9%NaCl,其余各组连续灌胃给予相应药物6周,6

  1. 25 Ways to Love Your Liver

    Science.gov (United States)

    ... Baby Boomers Get Tested Core Programs HE Webinar Disney 2014 5 Ways to Love Your Liver Liver ... Drive Away Liver Disease Liver Lowdown Aug 2013 Disney Marathon In The Field Healthy Foods Diet Recommendations ...

  2. General Information about Childhood Liver Cancer

    Science.gov (United States)

    ... Liver Cancer Prevention Liver Cancer Screening Research Childhood Liver Cancer Treatment (PDQ®)–Patient Version General Information About Childhood Liver Cancer Go to Health Professional Version Key Points Childhood ...

  3. Propylthiouracil for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2002-01-01

    Alcohol is the most common cause of liver disease in the Western world today. Randomised clinical trials have addressed the question whether propylthiouracil has any efficacy in patients with alcoholic liver disease.......Alcohol is the most common cause of liver disease in the Western world today. Randomised clinical trials have addressed the question whether propylthiouracil has any efficacy in patients with alcoholic liver disease....

  4. Radioembolization of liver tumors

    NARCIS (Netherlands)

    van den Hoven, AF

    2016-01-01

    Radioembolization is a therapy during which radioactive microspheres are administered through a microcatheter placed in the hepatic arterial vasculature in order to irradiate liver tumors from within. In the past decennium, this treatment has evolved as a safe and effective treatment option for pati

  5. LIVER AND BILIARY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    12.1 Liver function2003091 Treatment of acute hepatic failure by transplantation of microencapsulated xenogenic hepatocyte.ZHANG Weijie(张伟杰), et al. Instit Organ Transplant, Tongji Hosp, Huazhong Univ Sci & Technol, Wuhan 430030. World Chin J Digestol 2002; 10 (12): 1396-1398.

  6. Cirrhosis of the liver

    DEFF Research Database (Denmark)

    Bendtsen, Flemming; Larsen, Fin Stolze; Ott, Peter;

    2014-01-01

    Cirrhosis of the liver is a frequent and dangerous disease that causes numerous clinical contacts due to its complications. Competent and fast clinical decisions are often necessary in the acute setting and a broad clinical approach for the long-term problems due to the co-morbidity. Danish...

  7. Nonalcoholic fatty liver disease

    DEFF Research Database (Denmark)

    Patrick-Melin, A J; Kalinski, M I; Kelly, K R

    2009-01-01

    that features steatosis plus inflammation, termed nonalcoholic steatohepatitis (NASH), which may in turn progress to hepatic fibrosis, cirrhosis, and sub-acute liver failure. Thus, NAFLD and its subsequent complications create a significant health burden, and currently there is no effective treatment strategy...

  8. Acute Liver Failure Secondary to Niacin Toxicity

    Directory of Open Access Journals (Sweden)

    Marc A. Ellsworth

    2014-01-01

    Full Text Available A 17-year-old male was transferred to the pediatric intensive care unit for evaluation of acute liver failure. He was recently released from an alcohol treatment center with acute onset of chest pain. Cardiac workup was negative but he was found to have abnormal coagulation studies and elevated liver transaminases. Other evaluations included a normal toxicology screen and negative acetaminophen level. Autoimmune and infectious workups were normal providing no identifiable cause of his acute liver failure. He initially denied any ingestions or illicit drug use but on further query he admitted taking niacin in an attempt to obscure the results of an upcoming drug test. Niacin has been touted on the Internet as an aid to help pass urine drug tests though there is no evidence to support this practice. Niacin toxicity has been associated with serious multisystem organ failure and fulminant hepatic failure requiring liver transplantation. Pediatric providers should be aware of the risks associated with niacin toxicity and other experimental medical therapies that may be described on the Internet or other nonreputable sources.

  9. Stem cells in liver disease

    NARCIS (Netherlands)

    Poll, D. van

    2008-01-01

    Failure of the liver, the largest vital organ in the body, unequivocally results in death. Hepatic failure most commonly evolves over a period of several years as a result of chronic liver disease, most often viral hepatitis or alcoholic liver damage. In rarer cases, the organ shuts down within week

  10. Systemic abnormalities in liver disease

    Institute of Scientific and Technical Information of China (English)

    Masami Minemura; Kazuto Tajiri; Yukihiro Shimizu

    2009-01-01

    Systemic abnormalities often occur in patients with liver disease. In particular, cardiopulmonary or renal diseases accompanied by advanced liver disease can be serious and may determine the quality of life and prognosis of patients. Therefore, both hepatologists and non-hepatologists should pay attention to such abnormalities in the management of patients with liver diseases.

  11. Acute fatty liver in pregnancy.

    NARCIS (Netherlands)

    Tan, A.; Krieken, J.H.J.M. van; Peters, W.H.M.; Steegers, E.A.P.

    2002-01-01

    When confronted with liver abnormalities during the third trimester of pregnancy, one should consider acute fatty liver of pregnancy. The differential diagnosis with (pre-)eclampsia and HELLP syndrome is sometimes difficult. In these cases a liver biopsy is helpful though rarely performed during pre

  12. [Local treatment of liver tumors

    DEFF Research Database (Denmark)

    Pless, T.K.; Skjoldbye, Bjørn Ole

    2008-01-01

    Local treatment of non-resectable liver tumors is common. This brief review describes the local treatment techniques used in Denmark. The techniques are evaluated according to the evidence in literature. The primary local treatment is Radiofrequency Ablation of both primary liver tumors and liver...

  13. Improved transvenous liver biopsy needle

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Matzen, P; Christoffersen, P;

    1979-01-01

    A modified type of the standard transvenous cholangiography biopsy needle is described. The modified tranvenous liver biopsy needle caused only minimal artefactual changes of the liver biopsy specimens. The new type of biopsy needle is a modified Menghini needle. The conventional Menghini needle...... should be avoided for transvenous catheter biopsies because of risk of leaving catheter fragments in the liver....

  14. Pediatric obesity and the liver

    NARCIS (Netherlands)

    Koot, B.G.P.

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a frequent complication of obesity. In some of those with NAFLD, the fat accumulation in the liver will cause inflammation and fibrosis and can ultimately cause liver failure. In addition, in adults it has been established that NAFLD increases the risk of

  15. Research Progress of Liver Diseases

    Institute of Scientific and Technical Information of China (English)

    XU Lie-ming; JIA Ji-dong

    2005-01-01

    @@ Liver diseases are widespread in China.The disease mostly includes viral hepatitis,alcoholic or non alcoholic fatty degeneration or steatohepatitis, autoimmune liver disease,hepatic fibrosis/cirrhosis and hepatic cancer.The mechanism of most liver diseases was studied clearly in developed countries.

  16. A selective tropism of transfused oval cells for liver

    Institute of Scientific and Technical Information of China (English)

    Jian-Zhi Chen; Hai Hong; Jin Xiang; Ling Xue; Guo-Qiang Zhao

    2003-01-01

    AIM: To explore the biological behaviors of hepatic oval cells after transfused into the circulation of experimental animals.METHODS: Oval cells from male SD rat were transfused into the circulation of a female rat which were treated by a 2-AAF/CCl4 program, through caudal vein. Sex-determining gene sry which located on Y chromosome was examined by PCR and in situ hybridization technique in liver, kidney and spleen of the experimental animals, respectively.RESULTS: The results of the cell-transplant experiment showed that the srygene was detectable only in the liver but not in spleen and kidney of the experimental rats, and no signals could be detected in the control animals. It can be also morphologically proved that some exogenous cells had migrated into the parenchyma of the liver and settled there.CONCLUSION: The result means that there are exogenous cells located in the liver of the experimental animal and the localization is specific to the liver. This indicates that some "signal molecules" must exist in the circulation of the rats treated by 2-AAF/CCl4. These "signal molecules" might play an important role in specific localization and differentiation of transfused oval cells.

  17. Patogenesis of pipe-stem fibrosis of the liver (experimental observation on murine Schistosomiasis Patogenia da fibrose "pipe-stem" do fígado (observações experimentais na esquistossomose murina

    Directory of Open Access Journals (Sweden)

    Zilton A. Andrade

    1987-09-01

    Full Text Available Mice infected with 30 cercariae of Schistosoma mansoni developed portal and septal fibrosis due to the massive and concentrated deposition of eggs in the periportal areas which occurred following the 16th week after infection. The lesion resembled pipe-stem fibrosis seen in human hepatosplenic schistosomiasis in the following characters: portal fibrosis interconnecting portal spaces as well as portal spaces and central canals; portal inflammation; periovular granulomas; vascular obstruction and telangiectasia. The liver parenchyma maintained its normal architecture. Vascular injection techniques with Indian ink and vinylite revealed that the portal system developed numerous dilated collateral venules coming from the large and medium-sized portal branches, about 10 weeks after schistosome infection. The lodging of schistosome eggs into these collaterals resulted in granulomatous inflammation and fibrosis along all the portal tracts, thus forming the pipe-stem lesion. Although not readily demonstrable grossly, the pipe-stem fibrosis of murine schistosomiasis has many similarities with the human lesion and can be considered to have the same basic pathogenesis.Camundongos infectados com 30 cercárias do Schistosoma mansoni desenvolveram fibrose porta em virtude de um depósito progressivo e concentrado de ovos na região periportal, o que aconteceu a partir da 16ª semana da infecção. Esta fibrose certas características da chamada fibrose "pipe-stem" do homem vista na forma hepatoesplênica da esquistossomose, tais como obstrução das radiculas porta, telangiectasia, conexão fibrosa entre espaços porta e entre estes e veias centrais, além de certo grau de fibrose septal, presença dos granulomas em várias fases evolutivas e reação inflamatória crônica difusa, enquanto o parênquima hepático mantinha a sua estrutura lobular normal. As técnicas de injeção vascular com tinta da China e com vinilite feitas no sistema porta permitiram a

  18. Role of liver functions on liver cell mitosis

    Directory of Open Access Journals (Sweden)

    Takata,Tameyuki

    1974-06-01

    Full Text Available The control mechanism of mitosis in the regenerating rat liver was studied in relation to the cell functions. Partial hepatec· tomy induces a series of changes prior to the initiation of mitosis, i. e. decrease in serum glucose and albumin levels, loss of glycogen from liver cells, and increased lipid mobilization to liver cells. Massive supplies of glucose and fructose suppressed significantly hepatocellu. lar mitosis with suppression of lipid accumulation and preservation of glycogen in the liver cells and of blood sugar level. Homologous serum administration also suppressed the rate of liver cell mitosis after hepatectomy preventing the decrease in serum albumin level, but did not suppress the lipid accumulation in the liver. Starvation, which would relieve the liver cell from the work of detoxication of intesti. nal toxic products, did not show any suppressive effect on the mitotic rate of liver cells after partial hepatectomy in single animals. But starvation induced severe hypoglycemia, moderate hypoalbuminemia and loss of glycogen content in the liver. These changes in metabo. lism by starvation and partial hepatectomy were suppressed by con· jugating the animals with nonhepatectomized fed.partners by aortic anastomosis, and mitosis was suppressed in the residual liver of the fasting animals in this parabiosis. The results indicate that all the major functions of parenchymal live cells tested, sugar metabolism, serum albumin production, and detoxication, are closely related to the control of liver cell mitosis. Accumulation of lipids in the liver remnant after partial hepatectomy is thought to be for the compensa. tion of reduced glycogen storage and not concerned directly with the liver cell mitosis. Discussion was made briefly on the humoral factor and portal blood factor in relation to excess load of functions on resi. dual liver cells.

  19. Hemostasis and the diseased liver : a study on hemostatic disorders in liver disease and liver transplantation

    NARCIS (Netherlands)

    C.M. Bakker (Minke)

    1993-01-01

    textabstractIn this thesis studies on hemostatic disorders in liver cirrhosis and liver transplantation have been described. Aims of the work were to further investigate; 1. Whether (low-grade) DIC occurs in liver cirrhosis applying new quantitative tests, measuring thrombin-antithrombin Ill complex

  20. [Running through the liver transplantation].

    Science.gov (United States)

    Grecu, F

    2003-01-01

    An overview of the organization, timing and developing of the liver transplantation is difficult to be made in terms of multiple sequences and a great variety of activities during the developing of such activity. A well-trained transplant team must carry out the potential donor, the liver grafts manipulation and the graft receptor, in the condition of a competitive medical system. A summary presentation, showing the essentials of the proceedings in liver transplantation could be assimilated as a guide of multidisciplinary sequences that leads to the completion of the liver grafting. The common feature of all that means the liver transplantation and generally in organ transplantation is the performance and exactingness.

  1. Effects of anti-histamine treatment on liver injury triggered by small intestinal ischemia reperfusion in rats.

    Science.gov (United States)

    Huang, Pin-Jie; Gan, Xiao-Liang; Liu, Jian-Pei; Liu, De-Zhao; Wang, Yan-Ling; Hei, Zi-Qing

    2014-10-31

    Mast cell (MC) degranulation has been implicated in small intestinal ischemia reperfusion (IIR) injury, therein, inhibiting overproduction of histamine released from activated MC may provide promising strategies against IIR-mediated liver injuries. The aim of the present study was to explore whether anti-histamine treatment contribute to attenuating IIR-mediated liver injury. Adult SD rats were randomized into sham-operated group (S group), sole IIR group (IIR group), and IIR treated with Ketotifen, a histamine antagonist (IIR+K group), Cromolyn Sodium, a MC stabilizer (IIR+C group), and Compound 48/80, a MC degranulator (IIR+CP group), respectively. IIR was induced by superior mesenteric artery occlusion for 75 min followed by 4 h of reperfusion. The agents were intravenously administrated 5 min before reperfusion to induce different levels of histamine. Subsequently, serum concentrations of ALT, AST and histamine; levels of LDH,TNF-α, IL-8 and MDA as well as SOD activities in the liver were assessed. Histopathologic changes were also evaluated. IIR resulted in severe liver injury as demonstrated by significant increases in injury scores, with concomitant significant increases in serum ALT, AST and histamine levels, as well as LDH, TNF-α, IL-8, and MDA levels in the liver, accompanied by reduction in SOD activities (all P IIR vs. S). Treatments by Ketotifen and Cromolyn Sodium similarly markedly alleviated IIR-mediated liver injury as confirmed by significant reduction of the above biomedical changes whereas Compound 48/80 further aggravated IIR-mediated liver injury by dramatically enhancing the above biomedical changes. Data of our study suggest that anti-histamine treatments may provide promising benefits in alleviating liver injury triggered by IIR.

  2. Autoimmune paediatric liver disease

    Institute of Scientific and Technical Information of China (English)

    Giorgina Mieli-Vergani; Diego Vergani

    2008-01-01

    Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC),and de novo AIH after liver transplantation.AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA,type 1) or liver kidney microsomal antibody (LKM1,type 2).There is a female predominance in both.LKM1 positive patients tend to present more acutely,at a younger age,and commonly have partial IgA deficiency,while duration of symptoms before diagnosis,clinical signs,family history of autoimmunity, presence of associated autoimmune disorders,response to treatment,and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC.The clinical,biochemical, immunological,and histological presentation of ASC is often indistinguishable from that of AIH type 1.In both,there are high IgG,non-organ specific autoantibodies,and interface hepatitis.Diagnosis is made by cholangiography.Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates,times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However,the cholangiopathy can progress.There may be evolution from AIH to ASC over the years,despite treatment.De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH,including elevated titres of serum antibodies, hypergammaglobulinaemia,and histological findings of interface hepatitis,bridging fibrosis,and collapse.Like classical AIH,it responds to treatment with prednisolone and azathioprine.De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection.Whether this condition is a distinct entity or a form of

  3. Effects of Kanlijian (坎离煎) on Exercise Tolerance, Quality of Life, and Frequency of Heart Failure Aggravation in Patients with Chronic Heart Failure

    Institute of Scientific and Technical Information of China (English)

    JIANG Mei-xian; RUAN Xiao-fen; XU Yan

    2006-01-01

    Objective: To observe the effects of conventional therapy combined with Kanlijian (坎离煎,KLJ) on exercise tolerance, quality of life and frequency of heart failure aggravation in patients with chronic heart failure(CHF). Methods: Sixty. CHF patients differentiated as sufferring from the syndrome of Xin-Shen Yang deficiency were included in the study and randomly assigned at the ratio of 2: 1 into the KLJ group (n=39) and the control group(n = 21). All the patients were treated with conventional therapy of Western medicine, but to those in the KLJ group, KLJ was medicated additionally one dose daily with 24 wks as one therapeutic course. The efficacy on TCM syndrome and changes of scores on TCM syndrome were observed after treatment. The indexes, including 6-minute walking distance (6MWD), quality of life (QOL, accessed by LHFQ scoring), NYHA grade, hemodynamic indexes and reducing/withdrawal rate of diuretic and digoxin before and after treatment were recorded and compared. Also the frequency of re-admission due to aggravation of heart failure in one year's time were observed. Results: ( 1 ) The efficacy on TCM syndrome, improvement on scores of TCM syndrome, therapeutic effects on 6MWD, QOL, and NYHA grade in the KLJ group were superior to those in the control group. (2) Hemodynamic indexes after treatment, left ventricular fractional shortening (LVFS) and E peak/A peak (E/A), between the two groups had no significant difference, while left ventricular ejection fraction (LVEF) was increased significantly in the KLJ group, but with no obvious change in the control group. (3) The reducing/withdrawal rate of diuretic and digoxin in the KLJ group was significantly higher than that in the control group. (4) The 1-year frequency of re-admission significantly decreased in the KLJ group. Conclusion: The adjuvant treatment of KLJ on the basis of Western conventional therapy can significantly improve CHF patients' exercise tolerance, quality of life and cardiac function

  4. liver-enriched gene 1a and 1b encode novel secretory proteins essential for normal liver development in zebrafish.

    Directory of Open Access Journals (Sweden)

    Changqing Chang

    Full Text Available liver-enriched gene 1 (leg1 is a liver-enriched gene in zebrafish and encodes a novel protein. Our preliminary data suggested that Leg1 is probably involved in early liver development. However, no detailed characterization of Leg1 has been reported thus far. We undertook both bioinformatic and experimental approaches to study leg1 gene structure and its role in early liver development. We found that Leg1 identifies a new conserved protein superfamily featured by the presence of domain of unknown function 781 (DUF781. There are two copies of leg1 in zebrafish, namely leg1a and leg1b. Both leg1a and leg1b are expressed in the larvae and adult liver with leg1a being the predominant form. Knockdown of Leg1a or Leg1b by their respective morpholinos specifically targeting their 5'-UTR each resulted in a small liver phenotype, demonstrating that both Leg1a and Leg1b are important for early liver development. Meanwhile, we found that injection of leg1-ATG(MO, a morpholino which can simultaneously block the translation of Leg1a and Leg1b, caused not only a small liver phenotype but hypoplastic exocrine pancreas and intestinal tube as well. Further examination of leg1-ATG(MO morphants with early endoderm markers and early hepatic markers revealed that although depletion of total Leg1 does not alter the hepatic and pancreatic fate of the endoderm cells, it leads to cell cycle arrest that results in growth retardation of liver, exocrine pancreas and intestine. Finally, we proved that Leg1 is a secretory protein. This intrigued us to propose that Leg1 might act as a novel secreted regulator that is essential for liver and other digestive organ development in zebrafish.

  5. An acqueous extract of Bidens pilosa L. protects liver from cholestatic disease: experimental study in young rats Um extrato aquoso de Bidens pilosa L. protege o fígado da doença colestática: estudo experimental em ratos jovens

    Directory of Open Access Journals (Sweden)

    Marta Izabel Suzigan

    2009-10-01

    Full Text Available PURPOSE: To test the hepatoprotective effect of water extract from Bidens Pilosa L. (BPE in cholestatic liver disease induced by ligature and resection of the common bile ducts (LRBD in young rats. METHODS: We studied four groups of ten 21 days old (P21 Wistar rats, Group SW: sham operation and water; Group SD: sham operation and BPE (160 mg of fresh leaves/100 g of body weight/day; Group LW: LRBD and water and Group LD: LRBD and BPE daily. Pentobarbital sleeping time (PST and serum activities of aspartate aminotransferase (AST and of alanine aminotransferase (ALT were determined after the sacrifice (P70. A Ruwart's score for hepatic fibrosis (RS was given to each animal. Were employed two way ANOVA and the test of Tukey or a non-parametric test for multiple comparisons. RESULTS: There were statistically significant differences between LW and LD in the measurements of the PST ((means LW=390; LD=173, AST (means LW=8, LD=5, ALT (medians LW=2; LD=1 e RS (medians LW=2; LD=1. CONCLUSION: BPE could be used in the phytotherapy of the hepatic damage induced by chronic obstructive cholestasis, because protects liver function, decreases the rate of necrosis and liver fibrosis in cholestatic liver disease.OBJETIVO: Testar o efeito hepatoprotetor do extrato aquoso de Bidens pilosa L. (EBP na doença hepática induzida pela ligadura e ressecção do ducto biliar comum (LRDBC em ratos jovens. MÉTODOS: Estudamos ratos Wistar com 21º. dia de vida (P21 divididos em quatro grupos de 10 animais, Grupo SA: operação simulada e água; Grupo SD: operação simulada e EBP (160mg de folhas frescas/100g de peso corporal/dia; Grupo LA: LRDBC e água e Grupo LD: LRDBC e EBP diariamente. O tempo de sono por pentobarbital (TSP, aspartato (AST e alanina (ALT aminotransferase foram determinadas após o sacrifício (P70. O Score de Ruwart (SR para fibrose hepática foi atribuído para cada animal. Foi realizada análise de variância com dois fatores e pelo teste de Tukey

  6. Lipids changes in liver cancer

    Institute of Scientific and Technical Information of China (English)

    JIANG Jing-ting; XU Ning; ZHANG Xiao-ying; WU Chang-ping

    2007-01-01

    Liver is one of the most important organs in energy metabolism.Most plasma apolipoproteins and endogenous lipids and lipoproteins are synthesized in the liver.It depends on the integrity of liver cellular function,which ensures homeostasis of lipid and lipoprotein metabolism.When liver cancer occurs,these processes are impaired and the plasma lipid and lipoprotein patterns may be changed.Liver cancer is the fifth common malignant tumor worldwide,and is closely related to the infections of hepatitis B virus (HBV) and hepatitis C virus (HCV).HBV and HCV infections are quite common in China and other Southeast Asian countries.In addition,liver cancer is often followed by a procession of chronic hepatitis or cirrhosis,so that hepatic function is damaged obviously on these bases,which may significantly influence lipid and lipoprotein metabolism in vivo.In this review we summarize the clinical significance of lipid and lipoprotein metabolism under liver cancer.

  7. 双葛解酲丸对酒精性脂肪肝大鼠保护作用的实验研究%Experimental study on hepatic-protective effects of Shuangge Jiecheng Pill in rats of alcoholic fatty liver

    Institute of Scientific and Technical Information of China (English)

    罗华丽; 汪莹

    2012-01-01

    (LD) respectively. SG group were treated with different dosages of Shuangge Jiecheng Pill(20,10,5 g crude drug/(kg·d) and compared with TP group administrated by tiopronin tablet(40 mg/kg)for 4 weeks. The changes of ADH,GGT,ALT,AST,HTP,UA,AKP,organ indexes,fatty degeneration degree and inflammation activity of the rats in the different experimental groups were observed. Results:Compared with the control group,GGT,ALT,AST,UA,AKP and the liver indexes in the model group were obviously increased (P<0.05) while ADH,HTP,thoracic gland indexes and the body weights were decreased(P<0.01) and the pathologic hepatic tissue was seen. After the experiment and compared with the model group,the liver indexes in the TP and SG group of HD,MD and LD were obviously changed(P<0.01) and fatty degeneration degree and inflammation activity were lightened. And the indexes in SG group of HD were changed more obviously(P<0.01) than those of SG group of MD and LD. Conclusion-.Shuangge Jiecheng Pill is an effective method for alcoholic fatty liver disease by promoting the metabolism of alcohol,lessening the accumulation of fat in the liver,relieving the hepatocellular damage and resisting impairments to hepatic protein resulting from alcohol. The effect of SG group of HD is significantly superior to the others.

  8. The Involvement of Heat Shock Proteins in Murine Liver Regeneration

    Institute of Scientific and Technical Information of China (English)

    Qing Shi; Zhongjun Dong; Haiming Wei

    2007-01-01

    Partial hepatectomy (PHx) in mammals is a very common experimental model to investigate the process of liver regeneration. The surgery itself could give birth to a series of stresses, such as the temporary raise of body temperature and the ischaemia-reperfusion injury. Heat shock proteins (HSPs) were a family of stress-inducible proteins involved in maintaining cell homeostasis and regulating the immune system. In our study, we intended to investigate the expression and role of HSPs in liver regeneration. Using RT-PCR and Western blotting, we determined the expression in regenerating liver of HSP27, HSP60, HSP70 and HSP90 in mRNA level and protein level, respectively, with mice treated with sham operation as controls. We also used quercertin as an inhibitior of HSPs to explore their effects on liver regeneration. We found that hepatic expression of HSPs increased at the early phase of liver regeneration and declined to the constitutively low level later. Moreover, quercetin pretreatment delayed the progress of liver regeneration in mice via inhibition of HSPs. The results indicated that HSPs played an important role in liver regeneration.

  9. Liver iron transport

    Institute of Scientific and Technical Information of China (English)

    Ross M Graham; Anita CG Chua; Carly E Herbison; John K Olynyk; Debbie Trinder

    2007-01-01

    The liver plays a central role in iron metabolism. It is the major storage site for iron and also expresses a complex range of molecules which are involved in iron transport and regulation of iron homeostasis. An increasing number of genes associated with hepatic iron transport or regulation have been identified. These include transferrin receptors (TFR1 and 2), a ferrireductase (STEAP3), the transporters divalent metal transporter-1 (DMT1) and ferroportin (FPN) as well as the haemochromatosis protein, HFE and haemojuvelin (HJV),which are signalling molecules. Many of these genes also participate in iron regulatory pathways which focus on the hepatic peptide hepcidin. However, we are still only beginning to understand the complex interactions between liver iron transport and iron homeostasis. This review outlines our current knowledge of molecules of iron metabolism and their roles in iron transport and regulation of iron homeostasis.

  10. Polycystic Liver Disease

    Energy Technology Data Exchange (ETDEWEB)

    Linda, Nguyen, E-mail: nguyenli@einstein.edu [5501 Old York Road, Philadelphia, PA 19141 (United States)

    2016-03-25

    A 77-year-old African American male presented with intermittent abdominal pain for one week. He denied nausea, vomiting, diarrhea, constipation, fevers, anorexia, or weight loss. He denied a family history of liver disease, recent travel, or history of intravenous drug abuse. His vital signs were normal. Labs revealed total bilirubin of 1.5 mg/dl, hypoalbuminaemia 3.0 gm/dl and prolonged prothrombin time of 14.8 sec. Computed Tomography of the abdomen and pelvis with contrast showed multiple hepatic cysts with the largest cyst occupying the right abdomen, measuring 20.6 cm (Panel A and). This cyst had predominantly fluid attenuation, but also contained several septations. The patient underwent laparoscopic fenestration of the large hepatic cyst with hepatic cyst wall biopsy. Pathology revealed blood without malignant cells. The patient tolerated the procedure well with improvement of his abdominal pain and normalization of his liver function tests and coagulation profile.

  11. Fatty liver in childhood

    Institute of Scientific and Technical Information of China (English)

    Yesim; Ozturk; Ozlem; Bekem; Soylu

    2014-01-01

    Fatty liver is a growing health problem worldwide. It might evolve to nonalcoholic steatohepatitis, cirrhosis and cause hepatocellular carcinoma. This disease, which has increased because of eating habits, changes in food content and lifestyle, affects people from childhood. The most important risk factors are obesity and insulin resistance. Besides these factors, gender, ethnicity, genetic predisposition and some medical problems are also important. Cirrhosis in children is rare but is reported. Nonalcoholic fatty liver disease(NAFLD) has no specific symptoms or signs but should be considered in obese children. NAFLD does not have a proven treatment. Weight loss with family based treatments is the most acceptable management. Exercise and an applicable diet with low glycemic index and appropriate calorie intake are preferred. Drugs are promising but not sufficient in children for today.

  12. Hypoxia and fatty liver

    OpenAIRE

    Suzuki, Tomohiro; Shinjo, Satoko; Arai, Takatomo; Kanai, Mai; Goda, Nobuhito

    2014-01-01

    The liver is a central organ that metabolizes excessive nutrients for storage in the form of glycogen and lipids and supplies energy-producing substrates to the peripheral tissues to maintain their function, even under starved conditions. These processes require a considerable amount of oxygen, which causes a steep oxygen gradient throughout the hepatic lobules. Alcohol consumption and/or excessive food intake can alter the hepatic metabolic balance drastically, which can precipitate fatty li...

  13. Fatty liver in childhood

    OpenAIRE

    Ozturk,Yesim; Soylu, Ozlem Bekem

    2014-01-01

    Fatty liver is a growing health problem worldwide. It might evolve to nonalcoholic steatohepatitis, cirrhosis and cause hepatocellular carcinoma. This disease, which has increased because of eating habits, changes in food content and lifestyle, affects people from childhood. The most important risk factors are obesity and insulin resistance. Besides these factors, gender, ethnicity, genetic predisposition and some medical problems are also important. Cirrhosis in children is rare but is repor...

  14. Nonalcoholic Fatty Liver Disease

    OpenAIRE

    You, Jie; Huang, Sha; Huang, Gui-Qian; Zhu, Gui-Qi; Ma, Rui-Min; Liu, Wen-yue; Shi, Ke-Qing; Guo, Gui-Long; Chen, Yong-Ping; Braddock, Martin; Zheng, Ming-Hua

    2015-01-01

    Abstract Nonalcoholic fatty