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  1. Broad-spectrum matrix metalloproteinase inhibition curbs inflammation and liver injury but aggravates experimental liver fibrosis in mice.

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    Vincent E de Meijer

    Full Text Available BACKGROUND: Liver fibrosis is characterized by excessive synthesis of extracellular matrix proteins, which prevails over their enzymatic degradation, primarily by matrix metalloproteinases (MMPs. The effect of pharmacological MMP inhibition on fibrogenesis, however, is largely unexplored. Inflammation is considered a prerequisite and important co-contributor to fibrosis and is, in part, mediated by tumor necrosis factor (TNF-alpha-converting enzyme (TACE. We hypothesized that treatment with a broad-spectrum MMP and TACE-inhibitor (Marimastat would ameliorate injury and inflammation, leading to decreased fibrogenesis during repeated hepatotoxin-induced liver injury. METHODOLOGY/PRINCIPAL FINDINGS: Liver fibrosis was induced in mice by repeated carbon tetrachloride (CCl4 administration, during which the mice received either Marimastat or vehicle twice daily. A single dose of CCl4 was administered to investigate acute liver injury in mice pretreated with Marimastat, mice deficient in Mmp9, or mice deficient in both TNF-alpha receptors. Liver injury was quantified by alanine aminotransferase (ALT levels and confirmed by histology. Hepatic collagen was determined as hydroxyproline, and expression of fibrogenesis and fibrolysis-related transcripts was determined by quantitative reverse-transcription polymerase chain reaction. Marimastat-treated animals demonstrated significantly attenuated liver injury and inflammation but a 25% increase in collagen deposition. Transcripts related to fibrogenesis were significantly less upregulated compared to vehicle-treated animals, while MMP expression and activity analysis revealed efficient pharmacologic MMP-inhibition and decreased fibrolysis following Marimastat treatment. Marimastat pre-treatment significantly attenuated liver injury following acute CCl4-administration, whereas Mmp9 deficient animals demonstrated no protection. Mice deficient in both TNF-alpha receptors exhibited an 80% reduction of serum ALT

  2. 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

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

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    Nuño-Lámbarri, Natalia; Domínguez-Pérez, Mayra; Baulies-Domenech, Anna; Monte, Maria J.; Marin, Jose J. G.; Rosales-Cruz, Patricia; Souza, Verónica; Miranda, Roxana U.; Bucio, Leticia; Montalvo-Jave, Eduardo E.; Concepción Gutiérrez-Ruiz, María; García-Ruiz, Carmen

    2016-01-01

    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. PMID:27635189

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

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    Nuño-Lámbarri, Natalia; Domínguez-Pérez, Mayra; Baulies-Domenech, Anna; Monte, Maria J; Marin, Jose J G; Rosales-Cruz, Patricia; Souza, Verónica; Miranda, Roxana U; Bucio, Leticia; Montalvo-Jave, Eduardo E; Concepción Gutiérrez-Ruiz, María; García-Ruiz, Carmen; Fernández-Checa, José C; Gomez-Quiroz, Luis Enrique

    2016-01-01

    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. PMID:27635189

  5. Therapy with Minocycline Aggravates Experimental Rabies in Mice▿

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    Jackson, Alan C.; Scott, Courtney A.; Owen, James; Weli, Simon C.; Rossiter, John P.

    2007-01-01

    Minocycline is a tetracycline derivative with antiapoptotic and anti-inflammatory properties, and the drug has been shown to have beneficial effects in a variety of models of neurological disorders. The potentially neuroprotective role of minocycline was assessed in experimental in vitro and in vivo models of rabies virus infection. In this study, 5 nM minocycline did not improve the viability of embryonic mouse cortical and hippocampal neurons infected in vitro with the attenuated SAD-D29 st...

  6. Subchondral bone microstructural damage by increased remodelling aggravates experimental osteoarthritis preceded by osteoporosis

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    Bellido, Miriam; Lugo, Laura; Roman-Blas, Jorge A; Castañeda, Santos; Caeiro, Jose R; Dapia, Sonia; Calvo, Emilio; Largo, Raquel; Herrero-Beaumont, Gabriel

    2010-01-01

    Introduction Osteoporosis (OP) increases cartilage damage in a combined rabbit model of OP and osteoarthritis (OA). Accordingly, we assessed whether microstructure impairment at subchondral bone aggravates cartilage damage in this experimental model. Methods OP was induced in 20 female rabbits, by ovariectomy and intramuscular injections of methylprednisolone hemisuccinate for four weeks. Ten healthy animals were used as controls. At week 7, OA was surgically induced in left knees of all rabb...

  7. 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.

  8. FSH aggravates bone loss in ovariectomised rats with experimental periapical periodontitis

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    Qian, Hua; Guan, Xiaoyue; Bian, Zhuan

    2016-01-01

    Periapical bone loss is one of the prominent pathological and clinical features of periapical periodontitis. Previous studies have demonstrated that follicle-stimulating hormone (FSH) could directly affect skeletal remodelling by stimulating the formation and the function of osteoclasts in vitro and in vivo. However, the effect of FSH on periapical bone loss remained to be fully elucidated. In the current study, a rat model was established in order to verify the effect of FSH in experimental periapical lesions. It was identified that FSH aggravated the bone loss of periapical lesions. In addition, RANKL-, TRAP-, TNF-α- and IL-1β-positive cells were increased significantly in FSH-treated groups, which indicated that the function of FSH in bone loss may be mediated through the increasing activity of osteoclasts and the increased secretion of inflammatory cytokines. The results of the current study suggested that FSH, independent of oestrogen, may aggravate periapical bone loss by FSH receptors, which may serve an important role in the immune and inflammatory response of the host to root canal and periradicular infection during menopause. PMID:27510616

  9. Ultrafine particles in the airway aggravated experimental lung injury through impairment in Treg function.

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    Li, Guanggang; Cao, Yinghua; Sun, Yue; Xu, Ruxiang; Zheng, Zhendong; Song, Haihan

    2016-09-01

    Acute lung injury (ALI) is a life-threatening condition characterized by rapid-onset alveolar-capillary damage mediated by pathogenic proinflammatory immune responses. Since exposure to airway particulate matter (PM) could significantly change the inflammatory status of the individual, we investigated whether PM instillation in the airway could alter the course of ALI, using a murine model with experimental lung injury induced by intratracheal LPS challenge. We found that PM-treated mice presented significantly aggravated lung injury, which was characterized by further reductions in body weight, increased protein concentration in the bronchoalveolar lavage (BAL), and higher mortality rate, compared to control saline-treated mice. The PM-treated mice also presented elevated lung and systemic type 1 T helper cell (Th1) frequency as well as reduced lung regulatory T cell (Treg) frequency, which was associated with severity of lung injury. Further examinations revealed that the Treg function was impaired in PM-treated mice, characterized by significantly repressed transforming growth factor beta production. Adoptive transfer of functional Tregs from control mice to PM-treated mice significantly improved their prognosis after intratracheal LPS challenge. Together, these results demonstrated that first, PM in the airway aggravated lung injury; second, severity of lung injury was associated with T cell subset imbalance in PM-treated mice; and third, PM treatment induced quantitative as well as qualitative changes in the Tregs. PMID:27179778

  10. 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.

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

    OpenAIRE

    Shin-Ichi Yokota; Kaai Nakamura; Midori Ando; Hiroyasu Kamei; Fumihiko Hakuno; Shin-Ichiro Takahashi; Shigenobu Shibata

    2014-01-01

    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 hepa...

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

    Science.gov (United States)

    Yokota, Shin-Ichi; Nakamura, Kaai; Ando, Midori; Kamei, Hiroyasu; Hakuno, Fumihiko; Takahashi, Shin-Ichiro; Shibata, Shigenobu

    2014-01-01

    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. PMID:25383314

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

    BACKGROUND: The hippocampus undergoes apoptosis in experimental pneumococcal meningitis leading to neurofunctional deficits in learning and memory function. The aim of the present study was 1) to investigate hippocampal apparent diffusion coefficient (ADC) and volume with MRI during the course...... of experimental pneumococcal meningitis, 2) to explore the influence of accompanying bacteremia on hippocampal water distribution and volume, 3) and to correlate these findings to the extent of apoptosis in the hippocampus. METHODS: Experimental meningitis in rats was induced by intracisternal injection of live...... 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...

  20. 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

  1. 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.

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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

  5. 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.

  6. Extracorporeal membrane oxygenation as a bridge to liver transplantation for acute respiratory distress syndrome-induced life-threatening hypoxaemia aggravated by hepatopulmonary syndrome

    OpenAIRE

    Monsel, Antoine; Mal, Hervé; Brisson, Hélène; Luo, Rubin; Eyraud, Daniel; Vézinet, Corinne; Do, Chung Hi; Lu, Qin; Vaillant, Jean-Christophe; Hannoun, Laurent; Houssel, Pauline; Durand, François; Rouby, Jean-Jacques

    2011-01-01

    Introduction Combined with massive lung aeration loss resulting from acute respiratory distress syndrome, hepatopulmonary syndrome, a liver-induced vascular lung disorder characterized by diffuse or localized dilated pulmonary capillaries, may induce hypoxaemia and death in patients with end-stage liver disease. Methods The case of such a patient presenting with both disorders and in whom an extracorporeal membrane oxygenation was used is described. Results A 51-year-old man with a five-year ...

  7. Ideal Experimental Rat Models for Liver Diseases

    OpenAIRE

    Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok; Kim, Kyung Sik

    2011-01-01

    There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and dive...

  8. Ideal Experimental Rat Models for Liver Diseases.

    Science.gov (United States)

    Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok; Kim, Kyung Sik

    2011-05-01

    There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and diverse clinical symptoms, adverse reactions, and complications due to the pathological physiology. Also, it is not easy to reproduce identically various clinical situations in animal models. Recently, the Guide for the Care and Use of Laboratory Animals has tightened up the regulations, and therefore it is advisable to select the appropriate animals and decide upon the appropriate quantities through scientific and systemic considerations before conducting animal testing. Therefore, in this review article the authors examined various white rat animal testing models and determined the appropriate usable rat model, and the pros and cons of its application in liver disease research. The authors believe that this review will be beneficial in selecting proper laboratory animals for research purposes. PMID:26421020

  9. 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

  10. Oxidative Stress and Pulmonary Changes in Experimental Liver Cirrhosis

    Directory of Open Access Journals (Sweden)

    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.

  11. 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

  12. 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.

  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. Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research

    Science.gov (United States)

    Willebrords, Joost; Pereira, Isabel Veloso Alves; Maes, Michaël; Yanguas, Sara Crespo; Colle, Isabelle; Van Den Bossche, Bert; Da silva, Tereza Cristina; Oliveira, Cláudia P; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Cogliati, Bruno; Vinken, Mathieu

    2015-01-01

    Non-alcoholic fatty liver disease encompasses a spectrum of liver diseases, including simple steatosis, steatohepatitis, liver fibrosis and cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is currently the most dominant chronic liver disease in Western countries due to the fact that hepatic steatosis is associated with insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome and drug-induced injury. A variety of chemicals, mainly drugs, and diets is known to cause hepatic steatosis in humans and rodents. Experimental non-alcoholic fatty liver disease models rely on the application of a diet or the administration of drugs to laboratory animals or the exposure of hepatic cell lines to these drugs. More recently, genetically modified rodents or zebrafish have been introduced as non-alcoholic fatty liver disease models. Considerable interest now lies in the discovery and development of novel non-invasive biomarkers of non-alcoholic fatty liver disease, with specific focus on hepatic steatosis. Experimental diagnostic biomarkers of non-alcoholic fatty liver disease, such as (epi)genetic parameters and ‘-omics’-based read-outs are still in their infancy, but show great promise. . In this paper, the array of tools and models for the study of liver steatosis is discussed. Furthermore, the current state-of-art regarding experimental biomarkers such as epigenetic, genetic, transcriptomic, proteomic and metabonomic biomarkers will be reviewed. PMID:26073454

  16. Cyclosporin A induced toxicity in mouse liver slices is only slightly aggravated by Fxr-deficiency and co-occurs with upregulation of pro-inflammatory genes and downregulation of genes involved in mitochondrial functions

    NARCIS (Netherlands)

    Szalowska, Ewa; Pronk, T.E.; Peijnenburg, A.A.C.M.

    2015-01-01

    Background: The transcription factor farnesoid X receptor (FXR) governs bile acid and energy homeostasis, is involved in inflammation, and has protective functions in the liver. In the present study we investigated the effect of Fxr deficiency in mouse precision cut liver slices (PCLS) exposed to

  17. Effects of primary suture and fibrin sealant on hemostasis and liver regeneration in an experimental liver injury

    Institute of Scientific and Technical Information of China (English)

    Arif Hakan Demirel; Ozgur Taylan Basar; All Ulvi Ongoren; Erkut Bayram; Mustafa Kisakurek

    2008-01-01

    AIM:To investigate the effects of fibrin sealant on hemostasis and liver regeneration and intra-abdominal adhesions in an experimental liver injury.METHODS: Thirty-six Wistar rats were randomly divided into primary suture group (n=15), fibrin sealant group (n=15) and control group (n=6). A wedge resection was performed on the left lobe of the liver. In primary suture group, liver was sutured using polypropylene material, while fibrin glue was administrated on the liver surface in fibrin sealant group.RESULTS: More intra-abdominal adhesions were observed in the primary suture group compared to the fibrin sealant group on 3rd (2.50.5 vs 0.25.5, P =0.015), 10th(2.75.5 vs 0.50.6, P = 0.06) and 20th(1.75.5 vs 0.70.5, P = 0.015) postoperative days. Histopathological scores were better in the fibrin sealant group in comparison with the primary suture group on 3rd (8.75.5 vs 6.75.5, P = 0.006), 10th (7.50.0 vs 5.5.6, P = 0.021) and 20th(6.40.7 vs 3.20.6, P = 0.025) postoperative days.CONCLUSION: Out data suggest that fibrin sealant is preferred over primary suture in appropriate cases including liver trauma since it causes less intra-abdominal adhesions while allowing shorter hemostasis time as assessed in experimental liver trauma.

  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. Liver Mitochondrial Enzyme System In The Dynamics Of Experimental Leukemia

    Directory of Open Access Journals (Sweden)

    Gulmira Kasymova

    2012-10-01

    Full Text Available In rats with leukemia activity of liver mitochondrial enzymes are decreased at 6 months. Later, we noted compensatory activation of complexes II and III of the respiratory chain and transition to decompensation stage by final deadline. The activity of complex IV of the respiratory chain remains high. These changes result from increased lipid peroxidation and decreased activity of antioxidant protection enzymes.

  20. 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.

  1. 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.

  2. Clinical and Experimental Research of Primary Liver Cancer in China

    Institute of Scientific and Technical Information of China (English)

    WUMengchao

    2002-01-01

    Primary liver cancer (PLC) is one of the most common neoplasms and the second cancer-related cause of death in China, respresenting a major health problem. In China, PLC resulted in 20.40 deaths per lO0 000 per year,with 19.98 per 100 000 in cities and 23.59 per 100 000 inrural areas. Of all the newly enrolled PLC cases in the world each year, about 43% are found in the mainland of China.

  3. Experimental approach to the BNCT treatment of human liver

    International Nuclear Information System (INIS)

    The research program named Taormina, is concerned with an attempt to set up a method to use Boron neutron capture therapy for liver metastases in diffused tumours. According to our project, the liver will be explanted, treated with a solution of organic Boron compound, then irradiated in a thermal neutron field. Such modalities give the significant advantage to preserve the remaining patient organs from damage. A collaboration including nuclear physicists and surgeons of the University of Pavia planned the original research project. Researchers in the fields of chemistry and anatomy gave contributions during the experiment in their particular fields of competence. The conditions which must be satisfied to get a safe neutron treatment are given. The Thermal Column (TC) of the reactor Triga Mark II of the University of Pavia was modified to reach the objectives. The possibility to get useful values of T parameter by searching the modalities to take the greatest possible advantage from the so called blood-brain barrier is investigated. Such a barrier effect, due to the particular metabolism of tumour cells, produces Boron accumulation into tumour tissues while Boron solutions are circulating inside the blood channels. The results of processing of 24 rats are given. The rather poor statistics do not allow meaningful conclusions but only some optimistic hope

  4. Interleukins in chronic liver disease: lessons learned from experimental mouse models

    Directory of Open Access Journals (Sweden)

    Hammerich L

    2014-09-01

    . Experimental studies in mice help to define the exact influence of a specific cytokine on the outcome of chronic liver diseases and to identify useful therapeutic targets. Keywords: liver fibrosis, liver cirrhosis, liver cancer, interleukin, cytokine, T cell

  5. Experimental liver fibrosis research: update on animal models, legal issues and translational aspects

    OpenAIRE

    Liedtke, Christian; Luedde, Tom; Sauerbruch, Tilman; Scholten, David; Streetz, Konrad; Tacke, Frank; Tolba, René; Trautwein, Christian; Trebicka, Jonel; Weiskirchen, Ralf

    2013-01-01

    Liver fibrosis is defined as excessive extracellular matrix deposition and is based on complex interactions between matrix-producing hepatic stellate cells and an abundance of liver-resident and infiltrating cells. Investigation of these processes requires in vitro and in vivo experimental work in animals. However, the use of animals in translational research will be increasingly challenged, at least in countries of the European Union, because of the adoption of new animal welfare rules in 20...

  6. Prophylactic effects of humic acid AND#8211; glucan combination against experimental liver injury

    Directory of Open Access Journals (Sweden)

    Vaclav Vetvicka

    2015-09-01

    Full Text Available Aim: Despite intensive research, liver diseases represent a significant health problem and current medicine does not offer a substance able to significantly inhibit the hepatotoxicity leading to various stages of liver disease. Based on our previously published studies showing the protective effects of a glucan-humic acid combination, we focused on the hypothesis that combination of these two natural molecules can offer prophylactic protection against experimentally induced hepatotoxicity. Methods: lipopolysaccharide (LPS, carbon tetrachloride (CCl4 and ethanol were used to experimentally damage the liver. Levels of aspartate aminotransferase (AST, alanine transaminase (ALT, alkaline phosphatase (ALP, glutathione (GSH, superoxide dismutase (SOD and malondialdehyde (MDA, known to correspond to the liver damage, were assayed. Results: Using three different hepatotoxins, we found that in all cases, some samples of humic acid and most of all the glucan-humic acid combination, offer strong protection against liver damage. Conclusion: glucan-humic acid combination is a promising agent for use in liver protection. [J Intercult Ethnopharmacol 2015; 4(3.000: 249-255

  7. 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

  8. Circadian rhythms of liver physiology and disease: experimental and clinical evidence.

    Science.gov (United States)

    Tahara, Yu; Shibata, Shigenobu

    2016-04-01

    The circadian clock system consists of a central clock located in the suprachiasmatic nucleus in the hypothalamus and peripheral clocks in peripheral tissues. Peripheral clocks in the liver have fundamental roles in maintaining liver homeostasis, including the regulation of energy metabolism and the expression of enzymes controlling the absorption and metabolism of xenobiotics. Over the past two decades, research has investigated the molecular mechanisms linking circadian clock genes with the regulation of hepatic physiological functions, using global clock-gene-knockout mice, or mice with liver-specific knockout of clock genes or clock-controlled genes. Clock dysfunction accelerates the development of liver diseases such as fatty liver diseases, cirrhosis, hepatitis and liver cancer, and these disorders also disrupt clock function. Food is an important regulator of circadian clocks in peripheral tissues. Thus, controlling the timing of food consumption and food composition, a concept known as chrononutrition, is one area of active research to aid recovery from many physiological dysfunctions. In this Review, we focus on the molecular mechanisms of hepatic circadian gene regulation and the relationships between hepatic circadian clock systems and liver physiology and disease. We concentrate on experimental data obtained from cell or mice and rat models and discuss how these findings translate into clinical research, and we highlight the latest developments in chrononutritional studies.

  9. Genetics Home Reference: potassium-aggravated myotonia

    Science.gov (United States)

    ... myotonia Patient Support and Advocacy Resources (2 links) Muscular Dystrophy Association Resource list from the University of Kansas Medical Center Genetic Testing Registry (1 link) Potassium aggravated myotonia ClinicalTrials. ...

  10. 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

  11. Experimental liver fibrosis research: update on animal models, legal issues and translational aspects.

    Science.gov (United States)

    Liedtke, Christian; Luedde, Tom; Sauerbruch, Tilman; Scholten, David; Streetz, Konrad; Tacke, Frank; Tolba, René; Trautwein, Christian; Trebicka, Jonel; Weiskirchen, Ralf

    2013-01-01

    Liver fibrosis is defined as excessive extracellular matrix deposition and is based on complex interactions between matrix-producing hepatic stellate cells and an abundance of liver-resident and infiltrating cells. Investigation of these processes requires in vitro and in vivo experimental work in animals. However, the use of animals in translational research will be increasingly challenged, at least in countries of the European Union, because of the adoption of new animal welfare rules in 2013. These rules will create an urgent need for optimized standard operating procedures regarding animal experimentation and improved international communication in the liver fibrosis community. This review gives an update on current animal models, techniques and underlying pathomechanisms with the aim of fostering a critical discussion of the limitations and potential of up-to-date animal experimentation. We discuss potential complications in experimental liver fibrosis and provide examples of how the findings of studies in which these models are used can be translated to human disease and therapy. In this review, we want to motivate the international community to design more standardized animal models which might help to address the legally requested replacement, refinement and reduction of animals in fibrosis research. PMID:24274743

  12. [Some characteristics of metabolism in osteoarticular, cardiovascular, and liver tissues in "experimental osteochondrosis"].

    Science.gov (United States)

    Kniazieva, M V; Kaliman, P A; Tymoshenko, O P

    1995-01-01

    Considerable changes of collagen, glycosaminoglycans and calcium were observed both in vertebral tissues, bone, and in the heart, vessels, liver during development of "experimental osteochondrosis". The results have shown, that desintegration of biochemical processes in different tissues may be one of the factors affecting several diseases in one organism. PMID:8867314

  13. 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.

  14. Glycyrrhizin ameliorates metabolic syndrome-induced liver damage in experimental rat model.

    Science.gov (United States)

    Sil, Rajarshi; Ray, Doel; Chakraborti, Abhay Sankar

    2015-11-01

    Glycyrrhizin, a major constituent of licorice (Glycyrrhiza glabra) root, has been reported to ameliorate insulin resistance, hyperglycemia, dyslipidemia, and obesity in rats with metabolic syndrome. Liver dysfunction is associated with this syndrome. The objective of this study is to investigate the effect of glycyrrhizin treatment on metabolic syndrome-induced liver damage. After induction of metabolic syndrome in rats by high fructose (60%) diet for 6 weeks, the rats were treated with glycyrrhizin (50 mg/kg body weight, single intra-peritoneal injection). After 2 weeks of treatment, rats were sacrificed to collect blood samples and liver tissues. Compared to normal, elevated activities of serum alanine transaminase, alkaline phosphatase and aspartate transaminase, increased levels of liver advanced glycation end products, reactive oxygen species, lipid peroxidation, protein carbonyl, protein kinase Cα, NADPH oxidase-2, and decreased glutathione cycle components established liver damage and oxidative stress in fructose-fed rats. Activation of nuclear factor κB, mitogen-activated protein kinase pathways as well as signals from mitochondria were found to be involved in liver cell apoptosis. Increased levels of cyclooxygenase-2, tumor necrosis factor, and interleukin-12 proteins suggested hepatic inflammation. Metabolic syndrome caused hepatic DNA damage and poly-ADP ribose polymerase cleavage. Fluorescence-activated cell sorting using annexin V/propidium iodide staining confirmed the apoptotic hepatic cell death. Histology of liver tissue also supported the experimental findings. Treatment with glycyrrhizin reduced oxidative stress, hepatic inflammation, and apoptotic cell death in fructose-fed rats. The results suggest that glycyrrhizin possesses therapeutic potential against hepatocellular damage in metabolic syndrome. PMID:26400710

  15. 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

  16. PROTECTIVE EFFECT OF SALVIFOLIN ON LIVER MITOCHONDRIAL FUNCTION IN RATS WITH EXPERIMENTAL DIABETES

    OpenAIRE

    POZILOV MAMURJON KOMILJONOVICH; ASRAROV MUZAFFAR ISLAMOVICH; URMANOVA GULBAKHOR URUNBOEVNA; ESHBAKOVA KOMILA ALIBEKOVNA

    2015-01-01

    The influence of diterpenoid salvifolin on mitochondrial function was investigated. It was shown that in streptozotocin-induced diabetes damaged functional systems of rat liver mitochondria: respiration and oxidative phosphorylation, mitochondrial permeability transition pore and ATP -dependent potassium channel. Pharmacotherapy with salvifolin (intraperitoneally in dose of 3,5 mg/kg body weight) for 8 days has a protective effect on mitochondria in experimental diabetes, correction membrane ...

  17. Oxidized low-density-lipoprotein accumulation is associated with liver fibrosis in experimental cholestasis

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    Güldeniz Karadeniz

    2008-01-01

    Full Text Available OBJECTIVE: The aim of the present study was to examine the probable relationship between the accumulation of oxLDL and hepatic fibrogenesis in cholestatic rats. INTRODUCTION: There is growing evidence to support the current theories on how oxidative stress that results in lipid peroxidation is involved in the pathogenesis of cholestatic liver injury and fibrogenesis. One of the major and early lipid peroxidation products, OxLDL, is thought to play complex roles in various immuno-inflammatory mechanisms. METHODS: A prolonged (21-day experimental bile duct ligation was performed on Wistar-albino rats. Biochemical analysis of blood, histopathologic evaluation of liver, measurement of the concentration of malondialdehyde (MDA and superoxide-dismutase (SOD in liver tissue homogenates, and immunofluorescent staining for oxLDL in liver tissue was conducted in bile-duct ligated (n = 8 and sham-operated rats (n = 8. RESULTS: Significantly higher levels of MDA and lower concentrations of SOD were detected in jaundiced rats than in the sham-operated rats. Positive oxLDL staining was also observed in liver tissue sections of jaundiced rats. Histopathological examination demonstrated that neither fibrosis nor other indications of hepatocellular injury were found in the sham-operated group, while features of severe hepatocellular injury, particularly fibrosis, were found in jaundiced rats. CONCLUSION: Our results support the finding that either oxLDLs are produced as an intermediate agent during exacerbated oxidative stress or they otherwise contribute to the various pathomechanisms underlying the process of liver fibrosis. Whatever the mechanism, it is clear that an association exists between elevated oxLDL levels and hepatocellular injury, particularly with fibrosis. Further studies are needed to evaluate the potential effects of oxLDLs on the progression of secondary biliary cirrhosis.

  18. 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...

  19. 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

  20. Suppression of acute rejective response following orthotopic liver transplantation in experimental rats infected with Echinococcus multilocularis

    Institute of Scientific and Technical Information of China (English)

    LI Tao; ZHAO Jin-ming; ZHANG Yan; PAI Zu-la; ZHANG Wei; Tuxun Tuer-hongjiang; BAI Lei; WU Jiang; WEN Hao

    2011-01-01

    Background Hepatic alveolar echinococcosis (AE) is a parasitic disease in humans and caused by the Echinococcus multilocularis (Em). Orthotopic liver transplantation (OLT) may be the only effective treatment for end-stage hepatic AE. However, in some AE patients, extrahepatic Em can not be completely eliminated after OLT. We aimed to study whether the immunological changes caused by Em evasion may influence the rejective response.Methods Rat modles of AE were established by injecting the Em suspension into abdomen of Brown Norway (BN) rats.Three months later, in the experimental group, the liver was transplanted from Lewis (LEW) rats to Em-infected BN rats.In the control group, transplantation was from LEW rats to healthy BN rats. Liver tissue and peripheral blood (PB)samples were collected on days 1, 3, 5, and 7 after OLT. Liver tissue was analyzed after hematoxylin and eosin (H&E)staining; numbers of CD4, CD8, and CD28 on peripheral blood cells were detected by flow cytometry; and expression of the chemokine fractalkine (Fkn) was detected by reverse transcription PCR (RT-PCR). Interleukin-10 (IL-10) was measured in the serum by enzyme-linked immunosorbent assay (ELISA). In every group, eight BN rats were retained for observing survival time.Results The survival times of recipients in the experimental group were prolonged compared with those in the control group. The rejective response occurred later and was milder in the experimental group, percentage of CD4, CD8, CD28 T-cells and Fkn mRNA expression were lower in the experimental group. While the serum IL-10 levels were higher in the experimental group than those in the control group.Conclusions Acute rejective response after OLT was attenuated in the rats with Em infection, and the recipients survival time was prolonged. Em may play a role in this process by elevating IL-10 secretion, decreasing the effector T cells, inhibiting the expression of Fkn, which lead to reduce the inflammatory cells infiltration into

  1. 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.

  2. 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.

  3. Effect of oophorectomy and exogenous estrogen replacement on liver injury in experimental obstructive jaundice

    Institute of Scientific and Technical Information of China (English)

    Hamdi Bülent Ucan; Mehmet Kaplan; Bülent Salman; Utku Yilmaz; B Bülent Mentes; Cemalettin Aybay

    2008-01-01

    AIM: To investigate the role of estrogen on liver injury in an experimental obstructive jaundice model. METHODS: Three groups of female rats were constituted; group 1 was oophorectomized and given E2 (n = 14), group 2 was oophorectomized and given placebo (n = 14), and group 3 was sham operated (n = 14). Fourteen days following constitution of bile duct ligation, all groups were compared in terms of serum tests, histopathologic parameters, and tissue levels of IFN-γ, and IL-6. RESULTS: The parameters representing both the injury and/or the reactive response and healing were more pronounced in groups 1 and 2 (χ2 = 17. 2, χ2 =10. 20; χ2 = 12. 4, P < 0. 05). In the sham operated or E2 administered groups significantly lower tissue levels of IFN-γ, and higher IL-6 levels were found. In contrast, high IFN-γ, and low IL-6 tissue levels were found in the oophorectomized and placebo group (P < 0. 001). Kupffer cell alterations were observed to be more pronounced in the groups i and 3 (χ2 = 6. 13, P < 0. 05). CONCLUSION: Our study indicates that E2 impaired liver functions, accelerated both the liver damage and healing. In the conditions of bile duct obstruction, estrogen significantly changed the cytokine milieu in the liver.

  4. 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.

  5. The role of the liver in the protection by elemental diets against experimental colon cancer.

    Science.gov (United States)

    Barton, T; Lewin, M R

    1988-06-01

    This study investigates the mechanism whereby the elemental diet 'Vivonex' protects against experimental colon cancer. A total of 240 Wistar rats were randomly allocated to three dietary groups: (A) Vivonex HN, (B) Vivonex HN with 0.05% added cholesterol and (C) control standard powdered diet. All received a colon cancer-producing regimen of dimethylhydrazine (DMH) at a dose of 40 mg/kg BW, s.c., once weekly for 5 weeks. Ten weeks following the first DMH injection, then at 5 weekly intervals until the 40th week, 10 randomly selected rats from each dietary group were weighed, killed and necropsied. Total liver weights were recorded with samples kept for total lipid extraction and cholesterol and phospholipid assay. Each colon underwent macroscopic examination and all neoplasms were recorded. Results showed that control rats had a constant total liver lipid content over the 40 weeks and an increased incidence, number and development of colonic neoplasms with time. In contrast, Vivonex fed rats had significantly elevated total liver lipids, cholesterol and phospholipids over the 40 weeks compared to controls and a significantly reduced number and rate of development of colonic neoplasms. Rats fed on Vivonex + cholesterol had total liver lipids intermediate and significantly different from both the Vivonex and control groups and a similar result was seen in tumour development with time. This study shows that a Vivonex diet results in an increase in hepatic lipids, this effect being partially reversed with dietary cholesterol. The protective effect of Vivonex feeding in the DMH model of colon cancer may thus be mediated in part by the liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3411183

  6. 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

  7. Aggravation of Parkinson's disease by cinnarizine.

    OpenAIRE

    Martí Massó, J F; J. A. Obeso; Carrera, N; Martínez-Lage, J.M. (J.M.)

    1987-01-01

    The effect of cinnarizine on motor function in Parkinson's disease was evaluated in a randomised double-blind parallel study of 20 patients. Both groups were comparable in age, duration of the disease, dose of levodopa and degree of disability. A significant worsening of mobility was observed in patients treated with cinnarizine (75 mg bd), whilst no change was recorded in patients receiving placebo. Cinnarizine should be added to the list of drugs capable of aggravating Parkinson's disease.

  8. Time course of gene expression profiling in the liver of experimental mice infected with Echinococcus multilocularis.

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    Renyong Lin

    Full Text Available BACKGROUND: Alveolar echinococcosis (AE is a severe chronic parasitic disease which behaves like a slow-growing liver cancer. Clinical observations suggest that the parasite, Echinococcus multilocularis (E. multilocularis influences liver homeostasis and hepatic cell metabolism. However, this has never been analyzed during the time course of infection in the common model of secondary echinococcosis in experimental mice. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression profiles were assessed using DNA microarray analysis, 1, 2, 3 and 6 months after injection of E. multilocularis metacestode in the liver of susceptible mice. Data were collected at different time points to monitor the dynamic behavior of gene expression. 557 differentially expressed genes were identified at one or more time points, including 351 up-regulated and 228 down-regulated genes. Time-course analysis indicated, at the initial stage of E. multilocularis infection (month 1-2, that most of up-regulated pathways were related to immune processes and cell trafficking such as chemokine-, mitogen-activated protein kinase (MAPK signaling, and down-regulated pathways were related to xenobiotic metabolism; at the middle stage (month 3, MAPK signaling pathway was maintained and peroxisome proliferator-activated receptor (PPAR signaling pathway emerged; at the late stage (month 6, most of up-regulated pathways were related to PPAR signaling pathway, complement and coagulation cascades, while down-regulated pathways were related to metabolism of xenobiotics by cytochrome P450. Quantitative RT-PCR analysis of a random selection of 19 genes confirmed the reliability of the microarray data. Immunohistochemistry analysis showed that proliferating cell nuclear antigen (PCNA was increased in the liver of E. multilocularis infected mice from 2 months to 6 months. CONCLUSIONS: E. multilocularis metacestode definitely exerts a deep influence on liver homeostasis, by modifying a number of gene

  9. 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

  10. 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.

  11. Severe Brown Fat Lipoatrophy Aggravates Atherosclerotic Process in Male Mice.

    Science.gov (United States)

    Gómez-Hernández, Almudena; Beneit, Nuria; Escribano, Óscar; Díaz-Castroverde, Sabela; García-Gómez, Gema; Fernández, Silvia; Benito, Manuel

    2016-09-01

    Obesity is one of the major risk factors for the development of cardiovascular diseases and is characterized by abnormal accumulation of adipose tissue, including perivascular adipose tissue (PVAT). However, brown adipose tissue (BAT) activation reduces visceral adiposity. To demonstrate that severe brown fat lipoatrophy might accelerate atherosclerotic process, we generated a new mouse model without insulin receptor (IR) in BAT and without apolipoprotein (Apo)E (BAT-specific IR knockout [BATIRKO];ApoE(-/-) mice) and assessed vascular and metabolic alterations associated to obesity. In addition, we analyzed the contribution of the adipose organ to vascular inflammation. Brown fat lipoatrophy induces visceral adiposity, mainly in gonadal depot (gonadal white adipose tissue [gWAT]), severe glucose intolerance, high postprandial glucose levels, and a severe defect in acute insulin secretion. BATIRKO;ApoE(-/-) mice showed greater hypertriglyceridemia than the obtained in ApoE(-/-) and hypercholesterolemia similar to ApoE(-/-) mice. BATIRKO;ApoE(-/-) mice, in addition to primary insulin resistance in BAT, also showed a significant decrease in insulin signaling in liver, gWAT, heart, aorta artery, and thoracic PVAT. More importantly, our results suggest that severe brown fat lipoatrophy aggravates the atherosclerotic process, characterized by a significant increase of lipid depots, atherosclerotic coverage, lesion size and complexity, increased macrophage infiltration, and proinflammatory markers expression. Finally, an increase of TNF-α and leptin as well as a decrease of adiponectin by BAT, gWAT, and thoracic PVAT might also be responsible of vascular damage. Our results suggest that severe brown lipoatrophy aggravates atherosclerotic process. Thus, BAT activation might protect against obesity and its associated metabolic alterations. PMID:27414981

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

    Directory of Open Access Journals (Sweden)

    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.

  13. REGENERATIVE PECULIARITIES OF LIVER TISSUE AFTER HEMOSTASIS BY NONEQUILIBRIUM PLASMA ON 90TH AND 180TH DAY (EXPERIMENTAL STUDY

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    Ye. V. Semichev

    2014-01-01

    Full Text Available Liver damages occur to 17.8% of blunt abdominal trauma cases. Postoperative mortality in liver damage is a high. It amounts to 4–10% in case of stab wounds, to 30.4–35,2% in case of closed injury, to 39.3% in case of concomitant injury. Complete hemostasis without damage to organ parenchyma is needed for liver surgical operation.The aim of research is to evaluate the regenerative characteristics of liver tissue after hemostasis by nonequilibrium plasma in a long-term period.Material and methods. Research was performed on 20 laboratory rats, 3 experimental groups. 10 intact animals and 5 animals in groups on 90th and 180th day. Surgery is resection of liver left lobe and coagulation with cold plasma coagulator. The biochemical control (glucose, ALT, AST, total bilirubin, direct, alkaline phosphatase, total protein, urea, α-amylase, CRP, fibrinogen, aPTT, PTT, INR, morphological study of rat liver were performed.Results. After surgery with cold plasma hemostasis animals are active, early begin to eat. Fatal cases are not. Analysis of biochemical markers doesn't reveal statistically significant differences from the norm for the majority of indicators. Decrease of glucose concentration in the blood serum is observed in a long-term period. Histological analysis reveals an increase of the central and interlobular veins and moderate signs of edema on the 90th day. Hepatocytes with pronounced signs of protein and fatty degeneration are identified. Liver histology corresponds to the usual structure and is represented by liver lobules, separated by a small layer of connective tissue on the 180th day.Conclusion. Cold plasma coagulation in liver surgery showed effective hemostasis, minimal trauma of organ parenchyma, the lack of systemic effect and the subsequent complete regeneration of liver tissue in the treatment area.

  14. Therapeutic effect of Caspase-1 inhibitor on liver injury in experimental severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    张晓华; 李兆申; 屠振兴; 许国铭; 龚燕芳; 满晓华

    2004-01-01

    Objective: To assess the therapeutic effect of Caspase-1 inhibitor on liver injury in experimental severe acute pancreatitis (SAP). Methods: Forty-two SD rats were randomly divided into 3 groups: healthy controls (HC, n =6); SAP-S group (n = 18); SAP-ICE-I group (n = 18). SAP was induced by retrograde infusion of 5% sodium taurocholate into the bili-pancreatic duct in SD rats. HC rats underwent same surgical procedures and duct cannulation without sodium taurocholate. In SAP-S group, rats received the first intraperitoneal injection of isotonic saline 2 h after induction of acute pancreatitis, which was repeated after 12 h. In SAP-ICE-I group, rats were firstly given ICE inhibitor intraperitoneally 2 h after induction of pancreatitis. As in SAP-S group, this was repeated at 12 h. Survied rats were killed at certain time points, and all samples were obtained for subsequent analysis. Results: The serum levels of ALT, AST and IL-1β in SAPS group were (215.50 ±58.52) U/L, (372.17 ± 38.05) U/L, (276.77 ±44.92) pg/ml at 6 h, (396.67± 70.29) U/L,(548.50±75.29)U/L, (308.99± 34.95)pg/ml at 12 h, (425.17±86.33)U/L, (665.83±84.05)U/L, (311.60±46.51 ) pg/ml, respectively, which were increased significantly ( P < 0.01, vs HC). In SAP-ICE-I group, their levels were decreased significantly ( P < 0.01, vs SAP-S). Intrahepatic expressions of Caspase-1, IL-1β and IL-18 mRNA could be observed in HC, which were increased significantly in SAP-S group ( P < 0.01, vs HC). The expressions of IL-1β and IL-18mRNA were decreased significantly in SAP-ICE-I group ( P < 0.01, vs SAP-S), whereas Caspase-1 mRNA expressions had no significant differences ( P > 0.05). Caspase-1 inhibition had no effect on the severity of liver tissue damage. Conclusion: Caspase-1 activate cytokines, IL-1β and IL-18, play a pivotal role in the course of liver injury in SAP. Caspase-1 inhibitor can improve liver functions effectively.

  15. Effect of swine hepatitis E virus on the livers of experimentally infected Mongolian gerbils by swine hepatitis E virus.

    Science.gov (United States)

    Yang, Yifei; Shi, Ruihan; She, Ruiping; Soomro, Majid Hussain; Mao, Jingjing; Du, Fang; Zhao, Yue; Liu, Can

    2015-10-01

    Previous studies have shown that hepatitis E virus (HEV) can be transmitted between rats, pigs, cattle, rabbits, chicken, cats, and deer. Because wild and domestic rodents have anti-HEV antibodies, they are considered potential reservoirs of HEV. In the current study, Mongolian gerbils were experimentally infected with swine hepatitis E virus and the effects of this infection were investigated. After inoculation with HEV, the liver-to-body weight ratio increased at 7 dpi. Mongolian gerbils demonstrated significant increase (pPCR revealed that the copies of HEV RNA in the liver were detected at 7 dpi, and peaked at 28 dpi at a concentration of 7.73 logs g(-1). Using both light and electron microscopy, hepatic lesions were observed in the HEV inoculated animals. In the experimental group, characteristic viral hepatitis lesions were prominent in the liver. HEV antigen was detected in the liver by immunohistochemistry, and HEV ORF3 antigen was detectable in liver by Western blot. These results clearly demonstrate that viral load of HEV in livers was dynamic, and ultrastructural hepatic injury in HEV infected Mongolian gerbils and anti-HEV IgG positive seroconversion were observed during infection. PMID:26093307

  16. 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

  17. 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.

  18. Kupffer Cells Undergo Fundamental Changes during the Development of Experimental NASH and Are Critical in Initiating Liver Damage and Inflammation

    Science.gov (United States)

    Reid, D. T.; Reyes, J. L.; McDonald, B. A.; Vo, T.; Reimer, R. A.; Eksteen, B.

    2016-01-01

    Non-alcoholic fatty liver disease has become the leading liver disease in North America and is associated with the progressive inflammatory liver disease non-alcoholic steatohepatitis (NASH). Considerable effort has been made to understand the role of resident and recruited macrophage populations in NASH however numerous questions remain. Our goal was to characterize the dynamic changes in liver macrophages during the initiation of NASH in a murine model. Using the methionine-choline deficient diet we found that liver-resident macrophages, Kupffer cells were lost early in disease onset followed by a robust infiltration of Ly-6C+ monocyte-derived macrophages that retained a dynamic phenotype. Genetic profiling revealed distinct patterns of inflammatory gene expression between macrophage subsets. Only early depletion of liver macrophages using liposomal clodronate prevented the development of NASH in mice suggesting that Kupffer cells are critical for the orchestration of inflammation during experimental NASH. Increased understanding of these dynamics may allow us to target potentially harmful populations whilst promoting anti-inflammatory or restorative populations to ultimately guide the development of effective treatment strategies. PMID:27454866

  19. 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

  20. 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.

  1. [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.

  2. 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.

  3. Paraoxonase Activity and Expression Is Modulated by Therapeutics in Experimental Rat Nonalcoholic Fatty Liver Disease

    Science.gov (United States)

    Hussein, O.; Zidan, J.; Abu Jabal, K.; Shams, I.; Szvalb, S.; Grozovski, M.; Bersudsky, I.; Karry, R.; Aviram, M.

    2012-01-01

    Objective. The objective of the present study is to investigate the effect of rosiglitazone, metformin, ezetimibe, and valsartan (alone or in combinations) on paraoxonase (PON) activity and PON-mRNA expression in nonalcoholic fatty liver disease (NAFLD). Methods. 54 Male Sprague–Dawley rats were divided to 9 groups: chow diet group (15 weeks); methionine-choline-deficient diet (MCDD) group (15 weeks); MCDD-treated groups for the last 6 weeks with either metformin (M), rosiglitazone (R), metformin plus rosiglitazone (M+R), ezetimibe (E), valsartan (V), or a combination of R+M+V or of R+M+V+E for a total period of 15 weeks. Results. PON activities in serum and liver were decreased in MCDD rats. PON activity in serum increased significantly in all treatment groups. PON activity in liver was also increased significantly, except only in groups R, E, V, R+M+V, and R+M+V+E. Liver PON3 mRNA expression increased significantly in groups R+M, E, V, R+M+V, and R+M+V+E whereas liver PON2 mRNA expression increased significantly in MCDD, R+M, E, V, R+M+V, and R+M+V+E. Conclusions. PON activities in serum and liver were decreased in NAFLD. Treatment with insulin sensitizers, ezetimibe, and valsartan increased PON activity and reduced oxidative stress both in serum and liver. PMID:22536512

  4. Paraoxonase Activity and Expression Is Modulated by Therapeutics in Experimental Rat Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    O. Hussein

    2012-01-01

    Full Text Available Objective. The objective of the present study is to investigate the effect of rosiglitazone, metformin, ezetimibe, and valsartan (alone or in combinations on paraoxonase (PON activity and PON-mRNA expression in nonalcoholic fatty liver disease (NAFLD. Methods. 54 Male Sprague–Dawley rats were divided to 9 groups: chow diet group (15 weeks; methionine-choline-deficient diet (MCDD group (15 weeks; MCDD-treated groups for the last 6 weeks with either metformin (M, rosiglitazone (R, metformin plus rosiglitazone (M+R, ezetimibe (E, valsartan (V, or a combination of R+M+V or of R+M+V+E for a total period of 15 weeks. Results. PON activities in serum and liver were decreased in MCDD rats. PON activity in serum increased significantly in all treatment groups. PON activity in liver was also increased significantly, except only in groups R, E, V, R+M+V, and R+M+V+E. Liver PON3 mRNA expression increased significantly in groups R+M, E, V, R+M+V, and R+M+V+E whereas liver PON2 mRNA expression increased significantly in MCDD, R+M, E, V, R+M+V, and R+M+V+E. Conclusions. PON activities in serum and liver were decreased in NAFLD. Treatment with insulin sensitizers, ezetimibe, and valsartan increased PON activity and reduced oxidative stress both in serum and liver.

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

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    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.

  6. 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.

  7. 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

  8. 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+)

  9. Experimental hypothyroidism modulates the expression of the low density lipoprotein receptor by the liver

    International Nuclear Information System (INIS)

    The effect of exprimental hypothyroidism of the catabolism of plasma lipoproteins and on the expression of low density lipoprotein receptors by the liver was investigated in rats made hypothyroid by surgery. The animals developed mild hypercholesterolemia, mainly due to an increase of plasma low density lipoprotein, while other lipoprotein classes were only marginally affected. Kinetic studies using (125I)LDL indicated that a decreased fractional catabolic rate of the lipoprotein was responsible for this finding in agreement with the in vitro observation of a reduced binding of lipoproteins to liver membranes from hyperthyroid rats and with the demonstrations, by ligand blotting analysis, of a decreasd expression of lipoprotein receptors in liver membranes. These data suggest that hypothyroidism affects lipoprotein distribution also by decreasing the catabolism of low density lipoproteins by the liver (author)

  10. Non-peptidic analogs of the cell adhesion motif RGD prevent experimental liver injury.

    Science.gov (United States)

    Bruck, R; Hershkoviz, R; Lider, O; Shirin, H; Aeed, H; Halpern, Z

    2000-07-01

    In chronic viral hepatitis, autoimmune hepatitis, and some chronic cholestatic liver diseases, T lymphocytes serve as effector cells of the immunostimulatory processes. Cellular interactions of immune cells with extracellular matrix components are regulated primarily via the beta 1 subfamily of integrin receptors. The target epitope of several such integrin receptors is the Arg-Gly-Asp sequence, a cell adhesion motif shared by several matrix-associated adhesive glycoproteins. We review the use of synthetic non-peptidic analogs of RGD in the prevention of immune-mediated, concanavalin A-induced liver damage in mice and in inhibiting the development of liver cirrhosis in rats. The Con A-induced elevation of serum transaminases and tumor necrosis factor-alpha and the infiltration of liver tissue by inflammatory cells were inhibited by pretreatment of the mice with the synthetic RGD mimetics. In rats, the progression of thioacetamide-induced liver cirrhosis was markedly inhibited by the co-administration of the RGD mimetic SF-6,5. The compounds described here may be examined therapeutically for pathological conditions in the liver, manifested as necro-inflammation and fibrosis. PMID:10909422

  11. 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.

  12. Liver Manipulation Causes Hepatocyte Injury and Precedes Systemic Inflammation in Patients Undergoing Liver Resection

    OpenAIRE

    van de Poll, Marcel C. G.; Derikx, Joep P. M.; Buurman, Wim A.; Peters, Wilbert H. M.; Hennie M J Roelofs; Stephen J Wigmore; Dejong, Cornelis H C

    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 injury in patients undergoing liver resection.METHODS:Markers of hepatocyte injury (AST, GSTalpha, and L-FABP) and inflammation (IL-6) were measured in plasma of patients undergoing liver resection with ...

  13. Amarogentin regulates self renewal pathways to restrict liver carcinogenesis in experimental mouse model.

    Science.gov (United States)

    Sur, Subhayan; Pal, Debolina; Banerjee, Kaustav; Mandal, Suvra; Das, Ashes; Roy, Anup; Panda, Chinmay Kumar

    2016-07-01

    Amarogentin, a secoiridoid glycoside isolated from medicinal plant Swertia chirata, was found to restrict CCl4 /N-nitrosodiethyl amine (NDEA) induced mouse liver carcinogenesis by modulating G1/S cell cycle check point and inducing apoptosis. To understand its therapeutic efficacy on stem cell self renewal pathways, prevalence of CD44 positive cancer stem cell (CSC) population, expressions (mRNA/protein) of some key regulatory genes of self renewal Wnt and Hedgehog pathways along with expressions of E-cadherin and EGFR were analyzed during the liver carcinogenesis and in liver cancer cell line HepG2. It was observed that amarogentin could significantly reduce CD44 positive CSCs in both pre and post initiation stages of carcinogenesis than carcinogen control mice. In Wnt pathway, amarogentin could inhibit expressions of β-catenin, phospho β-catenin (Y-654) and activate expressions of antagonists sFRP1/2 and APC in the liver lesions. In Hedgehog pathway, decreased expressions of Gli1, sonic hedgehog ligand, and SMO along with up-regulation of PTCH1 were seen in the liver lesions due to amarogentin treatment. Moreover, amarogentin could up-regulate E-cadherin expression and down-regulate expression of EGFR in the liver lesions. Similarly, amarogentin could inhibit HepG2 cell growth along with expression and prevalence of CD44 positive CSCs. Similar to in vivo analysis, amarogentin could modulate the expressions of the key regulatory genes of the Wnt and hedgehog pathways and EGFR in HepG2 cells. Thus, our data suggests that the restriction of liver carcinogenesis by amarogentin might be due to reduction of CD44 positive CSCs and modulation of the self renewal pathways. © 2015 Wiley Periodicals, Inc. PMID:26154024

  14. Liver metastases

    Science.gov (United States)

    Metastases to the liver; Metastatic liver cancer; Liver cancer - metastatic; Colorectal cancer - liver metastases; Colon cancer - liver metastases; Esophageal cancer - liver metastases; Lung cancer - liver metastases; Melanoma - liver ...

  15. Biodistribution of Boron compounds in an experimental model of liver metastases for Boron Neutron Capture (BNCT) Studies

    International Nuclear Information System (INIS)

    Boron Neutron Capture Therapy (BNCT) is a binary treatment modality that involves the selective accumulation of 10B carriers in tumors followed by irradiation with thermal or epithermal neutrons. The high linear energy transfer alpha particles and recoiling 7Li nuclei emitted during the capture of a thermal neutron by a 10B nucleus have a short range and a high biological effectiveness. Thus, BNCT would potentially target neoplastic tissue selectively. In previous studies we demonstrated the therapeutic efficacy of different BNCT protocols in an experimental model of oral cancer. More recently we performed experimental studies in normal rat liver that evidenced the feasibility of treating liver metastases employing a novel BNCT protocol proposed by JEC based on ex-situ treatment and partial liver auto-transplant. The aim of the present study was to perform biodistribution studies with different boron compounds and different administration protocols to determine the protocols that would be therapeutically useful in 'in vivo' BNCT studies at the RA-3 Nuclear Reactor in an experimental model of liver metastases in rats. Materials and Methods. A total of 70 BDIX rats (Charles River Lab., MA, USA) were inoculated in the liver with syngeneic colon cancer cells DH/DK12/TRb (ECACC, UK) to induce the development of subcapsular metastatic nodules. 15 days post-inoculation the animals were used for biodistribution studies. A total of 11 protocols were evaluated employing the boron compounds boronophenylalanine (BPA) and GB-10 (Na210B1-0H10), alone or combined employing different doses and administration routes. Tumor, normal tissue and blood samples were processed for boron measurement by ICP-OES. Results. Several protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue, i.e. BPA 15.5 mg 10B/kg iv + GB-10 50 mg 10B/kg iv; BPA 46.5 mg 10B/kg ip; BPA 46.5 mg 10B/kg ip + iv; BPA 46

  16. 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.

  17. Hepatic mircocirculation and its role in development of pathological changes of the liver in experimental acute pancreatitis in rats

    Directory of Open Access Journals (Sweden)

    Zinenko D.Yu

    2008-01-01

    Full Text Available The purpose of the current study was to define the role of the hepatic mircocirculation in development of pathomorphological changes of the liver after the damage of pancreas in different rat models of experimental acute pancreatitis. The variants of 2 models were used: 1 model with intraperitoneal injection of L-arginin in dosage 3 g/kg; 4 g/kg and 5 g/kg; 2 model with injection 50 mkl 1%, 2,5% and 5% solutions of sodium taurocholat into pancreatic duct. The hystologic research of pancreas and liver were carried out in 1, 4, 8, 12, 24, 48 and 72 hours after initiation of inflammation. The visible reaction of hepatic mircocirculation in the experimental models of acute pancreatitis was depended on character of pathomorphological changes in pancreas. This reaction demonstrated the phase character including: 1 activation of hepatic circulation, first of all in portal component, against a background of pancreatic enzyme toxemia; 2 development of inflammatory, dystrophic, destructive and necrotic changes in hepatic parenchyme together with mircocirculation disorders against a background of pancreatic necrotic toxemia; 3 recovery and adaptation or decompensation processes in mircocirculation system of liver and hepatic parenchyme depending on the degree of pancreatogenic toxemia.

  18. Double-Balloon Catheter for Isolated Liver Perfusion: An Experimental Study

    International Nuclear Information System (INIS)

    Purpose: Further development of a previously described interventional method for isolated liver perfusion (ILP) with a new double-lumen balloon catheter, and evaluation of the side-effects of such isolation.Methods: In six pigs a double-balloon occlusion catheter was placed via the transjugular approach with its tip in the portal vein. One of the balloons was positioned in the inferior vena cava (IVC), cranial to the origin of the hepatic veins and the other balloon in the portal vein. By the transfemoral approach, a single-balloon occlusion catheter was placed in the IVC caudal to the origin of the hepatic veins. A third catheter was placed by the transfemoral route with the occlusion balloon in the proper hepatic artery. After inflation of all balloons 99Tcm-labelled human serum albumin was recirculated through the liver. The isolation was evaluated by repeated measurement of radioactivity levels in peripheral blood. Laboratory tests of liver and pancreas function, and hemoglobin, were taken before, at the end of, and 3 days after the procedure. Blood gases were tested at the beginning and end of the procedure.Results: One pig died during the procedure due to technical failure and was excluded from the study. In the other pigs leakage from the isolated liver to the systemic circulation increased slowly, up to 9.7% (mean) during 30 min of recirculation of the perfusate through the liver. Laboratory tests were normal in all pigs except insignificant acidosis directly after the procedure and the slight elevation of s-ALAT after 3 days.Conclusions: Only minor leakage from the liver to the systemic circulation was noted during ILP performed with a new, double-balloon catheter. There were no serious side effects

  19. The role of liver in leptin metabolism in experimental nephrotic syndrome

    OpenAIRE

    Ahmed, Mohamed Mahmoud; Amin, Ahmed Ibrahim; Fahmi, Abdelgawad Ali; Habib, Dawoud Fakhry; Kholousy, Naglaa Mohamed; Shalaby, Mostafa; Shanab, Asem Metwally Abo

    2012-01-01

    Leptin is a hormone influencing food intake, energy expenditure and body weight. It is pro-duced by adipocytes, exerts its effects on brain, endocrine pancreas and other organs by acti-vating trans-membrane receptors and is cleared from plasma mainly by the kidneys. Several studies have suggested that leptin's effects on metabolism are mediated by the liver. Our aim was to evaluate the role of the liver in the metabolism of leptin by comparing the serum leptin level in the portal vein with th...

  20. 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. PMID:21392496

  1. 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.

  2. 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...... that a weak hepatic benefit of RSV treatment is seen in prevention of steatosis only. This article is protected by copyright. All rights reserved....

  3. 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.

  4. 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

  5. [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.

  6. Experimental detection of iron overload in liver through neutron stimulated emission spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Kapadia, A J; Tourassi, G D; Sharma, A C [Department of Radiology, Duke Advanced Imaging Laboratories, Durham, NC 27705 (United States); Crowell, A S; Kiser, M R; Howell, C R [Department of Physics, Duke University, Durham, NC 27706 (United States)], E-mail: anuj.kapadia@duke.edu

    2008-05-21

    Iron overload disorders have been the focus of several quantification studies involving non-invasive imaging modalities. Neutron spectroscopic techniques have demonstrated great potential in detecting iron concentrations within biological tissue. We are developing a neutron spectroscopic technique called neutron stimulated emission computed tomography (NSECT), which has the potential to diagnose iron overload in the liver at clinically acceptable patient dose levels through a non-invasive scan. The technique uses inelastic scatter interactions between atomic nuclei in the sample and incoming fast neutrons to non-invasively determine the concentration of elements in the sample. This paper discusses a non-tomographic application of NSECT investigating the feasibility of detecting elevated iron concentrations in the liver. A model of iron overload in the human body was created using bovine liver tissue housed inside a human torso phantom and was scanned with a 5 MeV pulsed beam using single-position spectroscopy. Spectra were reconstructed and analyzed with algorithms designed specifically for NSECT. Results from spectroscopic quantification indicate that NSECT can currently detect liver iron concentrations of 6 mg g{sup -1} or higher and has the potential to detect lower concentrations by optimizing the acquisition geometry to scan a larger volume of tissue. The experiment described in this paper has two important outcomes: (i) it demonstrates that NSECT has the potential to detect clinically relevant concentrations of iron in the human body through a non-invasive scan and (ii) it provides a comparative standard to guide the design of iron overload phantoms for future NSECT liver iron quantification studies.

  7. 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.

  8. Cholinesterase activity in rat liver and serum during experimentally induced inflammation.

    Science.gov (United States)

    Simon, G; Budavári, I

    1977-01-01

    Cholinesterase activity of albino rats with acute local oedematous inflammation induced by turpentine, croton oil or Freund's adjuvant was elevated in the liver homogenate but decreased in the serum. Aprotinin administration prevented the decrease of serum activity. In the oedema fluid of rats treated with croton oil an enzyme with cholinester splitting activity was detected and it was shown to be identical with serum cholinesterase (EC 3. 1. 1. 8.). PMID:311577

  9. In Silico Analysis and Experimental Validation of Active Compounds from Cichorium intybus L. Ameliorating Liver Injury

    OpenAIRE

    Guo-Yu Li; Ya-Xin Zheng; Fu-Zhou Sun; Jian Huang; Meng-Meng Lou; Jing-Kai Gu; Jin-Hui Wang

    2015-01-01

    This study aimed at investigating the possible mechanisms of hepatic protective activity of Cichorium intybus L. (chicory) in acute liver injury. Pathological observation, reactive oxygen species (ROS) detection and measurements of biochemical indexes on mouse models proved hepatic protective effect of Cichorium intybus L. Identification of active compounds in Cichorium intybus L. was executed through several methods including ultra performance liquid chromatography/time of flight mass spectr...

  10. 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...

  11. 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.

  12. In Silico Analysis and Experimental Validation of Active Compounds from Cichorium intybus L. Ameliorating Liver Injury.

    Science.gov (United States)

    Li, Guo-Yu; Zheng, Ya-Xin; Sun, Fu-Zhou; Huang, Jian; Lou, Meng-Meng; Gu, Jing-Kai; Wang, Jin-Hui

    2015-01-01

    This study aimed at investigating the possible mechanisms of hepatic protective activity of Cichorium intybus L. (chicory) in acute liver injury. Pathological observation, reactive oxygen species (ROS) detection and measurements of biochemical indexes on mouse models proved hepatic protective effect of Cichorium intybus L. Identification of active compounds in Cichorium intybus L. was executed through several methods including ultra performance liquid chromatography/time of flight mass spectrometry (UPLC-TOF-MS). Similarity ensemble approach (SEA) docking, molecular modeling, molecular docking, and molecular dynamics (MD) simulation were applied in this study to explore possible mechanisms of the hepato-protective potential of Cichorium intybus L. We then analyzed the chemical composition of Cichorium intybus L., and found their key targets. Furthermore, in vitro cytological examination and western blot were used for validating the efficacy of the selected compounds. In silico analysis and western blot together demonstrated that selected compound 10 in Cichorium intybus L. targeted Akt-1 in hepatocytes. Besides, compound 13 targeted both caspase-1 and Akt-1. These small compounds may ameliorate liver injury by acting on their targets, which are related to apoptosis or autophagy. The conclusions above may shed light on the complex molecular mechanisms of Cichorium intybus L. acting on hepatocytes and ameliorating liver injury. PMID:26389883

  13. In Silico Analysis and Experimental Validation of Active Compounds from Cichorium intybus L. Ameliorating Liver Injury

    Directory of Open Access Journals (Sweden)

    Guo-Yu Li

    2015-09-01

    Full Text Available This study aimed at investigating the possible mechanisms of hepatic protective activity of Cichorium intybus L. (chicory in acute liver injury. Pathological observation, reactive oxygen species (ROS detection and measurements of biochemical indexes on mouse models proved hepatic protective effect of Cichorium intybus L. Identification of active compounds in Cichorium intybus L. was executed through several methods including ultra performance liquid chromatography/time of flight mass spectrometry (UPLC-TOF-MS. Similarity ensemble approach (SEA docking, molecular modeling, molecular docking, and molecular dynamics (MD simulation were applied in this study to explore possible mechanisms of the hepato-protective potential of Cichorium intybus L. We then analyzed the chemical composition of Cichorium intybus L., and found their key targets. Furthermore, in vitro cytological examination and western blot were used for validating the efficacy of the selected compounds. In silico analysis and western blot together demonstrated that selected compound 10 in Cichorium intybus L. targeted Akt-1 in hepatocytes. Besides, compound 13 targeted both caspase-1 and Akt-1. These small compounds may ameliorate liver injury by acting on their targets, which are related to apoptosis or autophagy. The conclusions above may shed light on the complex molecular mechanisms of Cichorium intybus L. acting on hepatocytes and ameliorating liver injury.

  14. Assessment of real-time method to detect liver parasite burden under different experimental conditions in mice infected with Plasmodium yoelii sporozoites.

    Science.gov (United States)

    Siddiqui, Arif Jamal; Bhardwaj, Jyoti; Goyal, Manish; Prakash, Kirtika; Soni, Awakash; Tiwari, Vishvanath; Puri, Sunil K

    2015-12-01

    Use of highly specific, sensitive and quantitative Real-Time PCR (qRT-PCR) based methods greatly facilitate the monitoring of experimental drug intervention and vaccination efficacy targeting liver stage malaria parasite. Here, in this study we have used qRT-PCR to detect the growing liver stage parasites following inoculation of Plasmodium yoelii sporozoite. Route of sporozoite administration and size of the sporozoite inoculums are two major determinants that affect the liver stage parasite load and therefore its detection and quantification. Thus, these factors need to be addressed to determine the accuracy of detection and quantification of Real-Time PCR method. Furthermore, applicability of quantitative RT-PCR system needs to be confirmed by analyzing the effect of different antimalarials on liver stage parasite burden. We have observed that parasite burden in mice infected via intravenous route was higher compared to that in subcutaneous, intradermal and intraperitoneal route infected mice. Moreover, this method detected liver stage parasite load with as low as 50 sporozoites. The inhibition studies with primaquine and atovaquone revealed inhibition of liver stage parasite and well correlated with patency and course of blood stage infection. This study characterized the simplicity, accuracy, and quantitative analysis of liver stage parasite development by real time PCR under different experimental conditions. Use of real time PCR method greatly improves the reproducibility and applicability to estimate the efficacy and potency of vaccine or drug candidates targeting liver stage parasite.

  15. Effect of interventional treatment with p53 on the invasion and metastasis of VX2 liver tumor in experimental rabbits

    International Nuclear Information System (INIS)

    Objective: To investigate the effect of interventional treatment with p53 on the invasion and metastasis of VX2 liver tumor in experimental rabbits. Methods: VX2 carcinoma cells were surgically implanted into the left hepatic lobe in 48 New Zealand white rabbits, and the rabbit hepatic carcinoma models were thus established. The rabbits were randomly divided into 4 groups with 12 rabbits in each group. After hepatic arterial catheterization was completed physiological saline (control group), Lipiodol (Group A), Ad-p53 (Group B) and Lipiodol+Ad-p53 (Group C) were respectively infused into the rabbits of four groups via common hepatic artery. One week after the procedure the rabbits were sacrificed and the livers were removed for the determination of matrix metalloprotein-2 (MMP-2), proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF) of the tumor with immunohistochemistry technique. Results: The tumor growth in study groups (group A, B and C) was markedly suppressed, which was significantly different in comparison with that in control group (P 0.05). The positive rates of MMP-2, PCNA and VEGF in group B and C were significantly lower than those in control group (P < 0.05). The positive rates of MMP-2, PCNA and VEGF of the rabbits with metastasis were markedly higher than those without metastasis(P < 0.05). MMP-2 bore a certain relationship with VEGF and PCNA (P < 0.05). Conclusion: The increase of the positive rates of MMP-2, PCNA and VEGF indicates that the tumor possesses higher possibility for developing metastasis, proliferation and vascular formation. The interventional treatment with Adp53 or Lipiodol+Ad-p53 can inhibit the growth, metastasis and vascular formation of VX2 liver tumor in experimental rabbits. (J Intervent Radiol, 2010, 19 : 800-804) (authors)

  16. Inhaled Methane Limits the Mitochondrial Electron Transport Chain Dysfunction during Experimental Liver Ischemia-Reperfusion Injury

    Science.gov (United States)

    Strifler, Gerda; Tuboly, Eszter; Szél, Edit; Kaszonyi, Enikő; Cao, Chun; Kaszaki, József; Mészáros, András; Boros, Mihály; Hartmann, Petra

    2016-01-01

    Background Methanogenesis can indicate the fermentation activity of the gastrointestinal anaerobic flora. Methane also has a demonstrated anti-inflammatory potential. We hypothesized that enriched methane inhalation can influence the respiratory activity of the liver mitochondria after an ischemia-reperfusion (IR) challenge. Methods The activity of oxidative phosphorylation system complexes was determined after in vitro methane treatment of intact liver mitochondria. Anesthetized Sprague-Dawley rats subjected to standardized 60-min warm hepatic ischemia inhaled normoxic air (n = 6) or normoxic air containing 2.2% methane, from 50 min of ischemia and throughout the 60-min reperfusion period (n = 6). Measurement data were compared with those on sham-operated animals (n = 6 each). Liver biopsy samples were subjected to high-resolution respirometry; whole-blood superoxide and hydrogen peroxide production was measured; hepatocyte apoptosis was detected with TUNEL staining and in vivo fluorescence laser scanning microscopy. Results Significantly decreased complex II-linked basal respiration was found in the normoxic IR group at 55 min of ischemia and a lower respiratory capacity (~60%) and after 5 min of reperfusion. Methane inhalation preserved the maximal respiratory capacity at 55 min of ischemia and significantly improved the basal respiration during the first 30 min of reperfusion. The IR-induced cytochrome c activity, reactive oxygen species (ROS) production and hepatocyte apoptosis were also significantly reduced. Conclusions The normoxic IR injury was accompanied by significant functional damage of the inner mitochondrial membrane, increased cytochrome c activity, enhanced ROS production and apoptosis. An elevated methane intake confers significant protection against mitochondrial dysfunction and reduces the oxidative damage of the hepatocytes. PMID:26741361

  17. 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.

  18. Inhaled Methane Limits the Mitochondrial Electron Transport Chain Dysfunction during Experimental Liver Ischemia-Reperfusion Injury.

    Directory of Open Access Journals (Sweden)

    Gerda Strifler

    Full Text Available Methanogenesis can indicate the fermentation activity of the gastrointestinal anaerobic flora. Methane also has a demonstrated anti-inflammatory potential. We hypothesized that enriched methane inhalation can influence the respiratory activity of the liver mitochondria after an ischemia-reperfusion (IR challenge.The activity of oxidative phosphorylation system complexes was determined after in vitro methane treatment of intact liver mitochondria. Anesthetized Sprague-Dawley rats subjected to standardized 60-min warm hepatic ischemia inhaled normoxic air (n = 6 or normoxic air containing 2.2% methane, from 50 min of ischemia and throughout the 60-min reperfusion period (n = 6. Measurement data were compared with those on sham-operated animals (n = 6 each. Liver biopsy samples were subjected to high-resolution respirometry; whole-blood superoxide and hydrogen peroxide production was measured; hepatocyte apoptosis was detected with TUNEL staining and in vivo fluorescence laser scanning microscopy.Significantly decreased complex II-linked basal respiration was found in the normoxic IR group at 55 min of ischemia and a lower respiratory capacity (~60% and after 5 min of reperfusion. Methane inhalation preserved the maximal respiratory capacity at 55 min of ischemia and significantly improved the basal respiration during the first 30 min of reperfusion. The IR-induced cytochrome c activity, reactive oxygen species (ROS production and hepatocyte apoptosis were also significantly reduced.The normoxic IR injury was accompanied by significant functional damage of the inner mitochondrial membrane, increased cytochrome c activity, enhanced ROS production and apoptosis. An elevated methane intake confers significant protection against mitochondrial dysfunction and reduces the oxidative damage of the hepatocytes.

  19. Proteasome β5i Subunit Deficiency Affects Opsonin Synthesis and Aggravates Pneumococcal Pneumonia.

    Science.gov (United States)

    Kirschner, Felicia; Reppe, Katrin; Andresen, Nadine; Witzenrath, Martin; Ebstein, Frédéric; Kloetzel, Peter-Michael

    2016-01-01

    Immunoproteasomes, harboring the active site subunits β5i/LMP7, β1i/LMP2, and β2i/MECL1 exert protective, regulatory or modulating functions during infection-induced immune responses. Immunoproteasomes are constitutively expressed in hematopoietic derived cells, constituting the first line of defense against invading pathogens. To clarify the impact of immunoproteasomes on the innate immune response against Streptococcus pneumoniae, we characterized the progression of disease and analyzed the systemic immune response in β5i/LMP7-/- mice. Our data show that β5i/LMP7 deficiency, which affected the subunit composition of proteasomes in murine macrophages and liver, was accompanied by reduced transcription of genes encoding immune modulating molecules such as pentraxins, ficolins, and collectins. The diminished opsonin expression suggested an impaired humoral immune response against invading pneumococci resulting in an aggravated systemic dissemination of S. pneumoniae in β5i/LMP7-/- mice. The impaired bacterial elimination in β5i/LMP7-/- mice was accompanied by an aggravated course of pneumonia with early mortality as a consequence of critical illness during the late phase of disease. In summary our results highlight an unsuspected role for immuno-subunits in modulating the innate immune response to extracellular bacterial infections. PMID:27100179

  20. 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.

  1. 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...

  2. Aggravation of symptomatic occipital epilepsy of childhood by carbamazepine

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

  4. Bipolar Radiofrequency Ablation Using Dual Internally Cooled Wet Electrodes: Experimental Study in Ex Vivo Bovine Liver

    International Nuclear Information System (INIS)

    To determine the optimized protocol for bipolar radiofrequency ablation (RFA), using dual internally cooled wet (ICW) electrodes in the ex vivo bovine liver. RFA was applied to the explanted bovine liver, using two 3 cm active tip electrodes with 3.5 cm spacing. A total of 25 ablation zones were created by five groups; group A: 70 W-20 minute (min), group B: 70 W-25 min, group C: 90 W-15 min, group D: 90 W-20 min, and group E: 90 W-25 min. We measured the total energy and size of ablation zones with a color of grey or pink. Statistical analysis was done using Kruskal Wallis test and Mann Whitney U-test. The mean energy, mean volume of ablation zone with grey and pink color of groups A to E were 16.7, 23.9, 16.7, 21.8, 29.2 kcal, 25.7, 34.3, 29.5, 36.2, 45.2 cm3, and 60.0, 88.0, 71.5, 87.4, 104.5 cm3, respectively. Those were significantly different (p < 0.05). The volume of ablation zone of group E with grey color was larger than groups A, B and C (p < 0.05). Bipolar RFA, using dual ICW electrodes, can produce a large ablation zone with the protocol of 90 W-25 min.

  5. 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.

  6. [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.

  7. 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.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    –80 km/h, slippery road surface, and location of the crash on road sections are aggravating infrastructure factors, while the availability of cycling paths and dense urban development are mitigating factors. Heavy vehicle involvement and conflicts between cyclists going straight or turning left and other......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...

  9. Injection of recombinant tumor necrosis factor directly into liver metastases: an experimental and clinical approach

    NARCIS (Netherlands)

    J.N.M. IJzermans (Jan); M. Scheringa (Marcel); G. van der Schelling; R.A. Geerling; R.L. Marquet (Richard); J. Jeekel (Hans)

    1992-01-01

    markdownabstract__Abstract__ Systemic treatment with tumor necrosis factor (TNF) is associated with side-effects, limiting its clinical use in the treatment of malignancies. To investigate the feasibility of other routes of administration experimental and clinical studies were started to establish

  10. The subjective meaning of xerostomia—an aggravating misery

    OpenAIRE

    Folke, Solgun; Paulsson, Gun; Fridlund, Bengt; Söderfeldt, Björn

    2010-01-01

    Xerostomia, the subjective sensation of dry mouth, is associated with qualitative and quantitative changes of saliva. Poor health, certain medications and radiation therapy constitute major risk factors. To gain further understanding of this condition the present study explored the main concern of xerostomia expressed by affl icted adults. Qualitative interviews were conducted with 15 participants and analysed according to the grounded theory method. An aggravating misery was identifi ed as t...

  11. 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.

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

    OpenAIRE

    Maria de Fatima Guerreiro Godoy; Livia Maria Pereira de Godoy; Stelamarys Barufi; José Maria Pereira de Godoy

    2014-01-01

    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), i...

  13. 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.

  14. Garlic decreases liver and kidney receptor for advanced glycation end products expression in experimental diabetes.

    Science.gov (United States)

    Al-Qattan, Khaled K; Mansour, Mohamed H; Thomson, Martha; Ali, Muslim

    2016-06-01

    The up-regulation of the receptor for advanced glycation end products (RAGE) has been implicated as a major mediator in the development and progression of diabetic nephropathy and hepatic fibrogenesis. The present study was designed to investigate the potential of garlic (Allium sativum L.) to modulate the level of expression of RAGE in renal and hepatic tissues of diabetic rats. Three groups of rats were studied after 8 weeks following diabetes induction: normal, streptozotocin-induced diabetic (control diabetic), and garlic-treated diabetic rats. A polyclonal antibody of proven specificity to RAGE indicated in immunohistochemical assays that RAGE labeling was significantly increased in renal and hepatic tissues of control diabetic rats compared to the normal group. The increased RAGE labeling involved mesangial cells in glomeruli exhibiting signs of mesangial expansion, mesangial nodule formation and glomerulosclerosis. In the liver, a significant up-regulation of RAGE was observed in hepatocytes and bile ducts and vessels in portal tracts. In 2-dimensional Western blots, RAGE expression in both tissues was dominated by heterogeneous charge variants, represented by 46-50kDa isoforms with more basic pIs compared to their counterparts in normal rats. Compared to control diabetic rats, RAGE labeling in the garlic-treated diabetic group was significantly reduced throughout renal and hepatic regions and was marked by the expression of 43-50kDa acidic charge variants comparable to those observed in normal rats. The capacity of garlic to modulate diabetes-induced up-regulation of selective RAGE polymorphic variants may be implicated in attenuating the detrimental consequences of excessive RAGE signaling manifested by diabetes-associated disorders. PMID:26968224

  15. Experimental and clinical studies on liver regeneration and hepatocellular carcinoma. Roles of redox proteins, iron homeostasis and multikinase inhibition.

    OpenAIRE

    Mollbrink, Annelie

    2013-01-01

    Compensatory liver regeneration is triggered by chronic liver injury or surgery and is crucial to maintain tissue homeostasis. The underlying mechanisms which include a whole battery of complex signaling events have been thoroughly studied for decades. The majority of hepatocellular carcinomas develop in a highly proliferative environment caused by underlying chronic liver disease in which lost liver tissue must be restored to meet the needs of the organism. The chronic inflammatory condition...

  16. 42 CFR 93.408 - Mitigating and aggravating factors in HHS administrative actions.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Mitigating and aggravating factors in HHS... and Human Services Research Misconduct Issues § 93.408 Mitigating and aggravating factors in HHS... conserve public funds. HHS considers aggravating and mitigating factors in determining appropriate...

  17. Effect of interferon-alpha on experimental septal fibrosis of the liver - study with a new model

    Directory of Open Access Journals (Sweden)

    Marcia Maria de Souza

    2001-04-01

    Full Text Available Interferon-alpha is used in antiviral therapy in humans, mainly for viral hepatitis B and C. An anti-fibrotic effect of interferon has been postulated even in the absence of anti-viral response, which suggests that interferon directly inhibits fibrogenesis. Rats infected with the helminth Capillaria hepatica regularly develop diffuse septal fibrosis of the liver, which terminates in cirrhosis 40 days after inoculation. The aim of this study was to test the anti-fibrotic effect of interferon in this experimental model. Evaluation of fibrosis was made by three separate methods: semi-quantitative histology, computerized morphometry and hydroxyproline measurements. Treatment with interferon-alpha proved to inhibit the development of fibrosis in this model, especially when doses of 500,000 and 800,000 IU were used for 60 days. Besides confirming the anti-fibrotic potential of interferon-alpha on a non-viral new experimental model of hepatic fibrosis, a clear-cut dose-dependent effect was observed.

  18. 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

  19. 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.

  20. 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.

  1. The Vitamine D3 Analogue (1α Hydroxyvitamin D3) Aggravates Carbon Tetrachloride-Induced Hepatotoxicity In Albino Rats

    International Nuclear Information System (INIS)

    Provitamin D, cholecalciferol, undergoes hydroxylation at the 25 and the 1α position in the liver and the kidney, respectively, before it turns into a hormonally active form regulating calcium homeostasis. The main purpose of the present study is to assess the potential of the 1α hydroxyvitamin D3 analogue to aggravate the ability of carbon tetrachloride (CCl4) to cause hepatotoxicity in albino rats. For this purpose, four groups of male albino rats, each of five, were used as follow: control group (G 1) received no treatment, CCl4 treated group (G 2) received CCl4 at a dose of 0.2 ml/100 g body weight in sunflower oil (1/1) v/v ratio two times per week for three weeks subcutaneously, 1α hydroxyvitamin D3 treated group (G 3) received a total dose of 5 ng/g body weight of 1α hydroxyvitamin D3 dissolved in propyl alcohol divided into six doses each given twice weekly for three weeks via the subcutaneous route, and CCl4 + 1α hydroxyvitamin D3 treated group (G 4) received the same dose of CCl4 and 1α hydroxyvitamin D3 concomitantly as previously described. Liver tissues from sacrificed animals were fixed in 10% formalin before sectioning and stained with eosin and hematoxyline then were examined histopathologically. Sera from control and treated animals were separated from blood and examined for ALT, AST, alkaline phosphatase and LDH levels. Serum total protein, albumin, globulin, A/G, bilirubin, creatinine, phosphorous and Ca levels were also monitored. Data from the present study showed that administration of 1α hydroxyvitamin D3 aggravated CCl4-induced hepatotoxicity as evidenced by the exacerbation of the rise in serum ALT, AST, alkaline phosphatase levels. The analogue, however, had no effect on serum liver enzymes in CCl4 untreated rats. Though, CCl4 caused significant impairment of kidney function as shown by the rise in serum creatinine and urea levels which were differentially affected by the analogue. In conclusion, the 1α hydroxyvitamin D3 compound

  2. 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.

  3. PP005. Vitamin D depletion aggravates hypertension in transgenic rats

    DEFF Research Database (Denmark)

    Bjørkholt Andersen, Louise; Herse, Florian; Christesen, Henrik Thybo;

    2013-01-01

    overexpressing the human renin and angiotensinogen genes, group 1 (n=18) received vitamin D depleted chow; group 2 (n=15) standard chow and intraperitoneal paricalcitol at 800ng/kg thrice weekly; and group 3 (n=15) standard chow and vehicle injections. Blood pressure (tail cuff) and 24-h albuminuria were...... found between groups in mortality or proteinuria. CONCLUSION: Short-term vitamin D depletion aggravated hypertension and end-organ damage in a rat model of angiotensin II-induced hypertension. Short-term interventions with high-dose vitamin D analogues had no protective effect....

  4. Liver Transplant

    Science.gov (United States)

    ... Home > Your Liver > Liver Disease Information > Liver Transplant Liver Transplant Explore this section to learn more about liver ... harmful substances from your blood. What is a liver transplant? A liver transplant is the process of replacing ...

  5. [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.

  6. 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.

  7. 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.

  8. 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. PMID:25330389

  9. Protective Effect of Vitamin C and Ginseng on Experimental Liver and Kidney Injuries Induced by Insecticide Profenophos In Male Rats

    Directory of Open Access Journals (Sweden)

    Fatma A. Morsy

    2003-03-01

    Full Text Available The present investigation deals with histopathological and histochemical studies of profenophos on liver and kidney of male albino rats and the protective effects of vitamin C and ginseng to reduce the deleterious effect induced by profenophos. Oral administration of profenophos at dose level of 1/10 LD50 for 15 successive days induced histological changes in liver and kidney. No histological or histochemical change could be detected in liver and kidney of rats treated with each of vitamin C and ginseng. Profenophos treatment also resulted in histochemical changes in liver and kidney including decrease in protein granules and marked decrease in DNA and mucopolysaccharides content. Administration of vitamin C (0.01/ 100 g b.w and ginseng (20 mg/ kg b.w to profenophos treated animals resulted in an improvement in histological picture of liver and kidney as well as the histochemical parameters.

  10. 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.

  11. [The characteristic of proliferative activity of thymocytes and peripheral blood lymphocytes in the offspring of females with experimental chronic liver diseases of various aetiology].

    Science.gov (United States)

    Briukhin, G V; Fedosov, A A

    2006-01-01

    The aim of the study was a comparative analysis of the proliferative activity of thymocytes and peripheral blood lymphocytes in the offspring of female rats with chronic liver pathology of various genesis. In adult female Wistar rats toxic and autoimmune forms of liver lesions were modeled. The offspring of these experimental animals was studied at different time points of postnatal ontogenesis. Proliferative activity of thymocytes and lymphocytes was estimated by counting the proportion of cells with multiple nucleolar organizing regions (AgNORs) and using the cytofluorometric method with acridine orange. In the offspring of experimental animals, the depression of proliferative activity of thymocytes as well as the increase of the proliferative activity of peripheral blood lymphocytes were found at all the time points studied. This was indicated by a change in a relative number of AgNORs-activated cells and a decrease of nucleic acid content in cortical thymocytes. PMID:17201321

  12. Adaptive rewiring aggravates the effects of species loss in ecosystems.

    Science.gov (United States)

    Gilljam, David; Curtsdotter, Alva; Ebenman, Bo

    2015-01-01

    Loss of one species in an ecosystem can trigger extinctions of other dependent species. For instance, specialist predators will go extinct following the loss of their only prey unless they can change their diet. It has therefore been suggested that an ability of consumers to rewire to novel prey should mitigate the consequences of species loss by reducing the risk of cascading extinction. Using a new modelling approach on natural and computer-generated food webs we find that, on the contrary, rewiring often aggravates the effects of species loss. This is because rewiring can lead to overexploitation of resources, which eventually causes extinction cascades. Such a scenario is particularly likely if prey species cannot escape predation when rare and if predators are efficient in exploiting novel prey. Indeed, rewiring is a two-edged sword; it might be advantageous for individual predators in the short term, yet harmful for long-term system persistence. PMID:26400367

  13. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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

  16. [Relative increase and metacritic aggravation in the diagnosis of anicteric cholestasis].

    Science.gov (United States)

    Albot, G; Geraudias, P; Kind, M

    1975-02-14

    The authors report 3 cases and report the diagnostic usefulness of two signs of minor cholestasis described by one of them in 1966. A relative increase, in the absence of obvious virus hepatitis or cirrhosis, of the serum bilirubin, cholesterol, lipids and alkaline phosphatase, together with B.S.P. excretion. suggest minor cholestasis. The sign of "metacritical aggravation" when there is some suspicion of minor cholestasis, the supervision of the course of the disease, or a retrospective inquiry, permit, in the presence of minor symptoms, such as, pain, fever, jaundice, or pruritus, one to make the diagnosis of minor cholestasis. The latter is due either to the presence of small gall stones in the common bile duct, or to inflammation of the ampulla of Vater, or sphincter of Oddi, a Vaterian ampulloma, pancreatitis, or following damage to the common bile duct. In practice, liver biopsy confirms the diagnosis, and intravenous cholangiography, by the perfusion method, is usually able to demonstrate obstruction of the common bile duct. PMID:169583

  17. 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.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    Berthold Hocher

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

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. Experimental Periodontitis Results in Prediabetes and Metabolic Alterations in Brain, Liver and Heart: Global Untargeted Metabolomic Analyses

    Science.gov (United States)

    Ilievski, Vladimir; Kinchen, Jason M; Prabhu, Ramya; Rim, Fadi; Leoni, Lara; Unterman, Terry G.; Watanabe, Keiko

    2016-01-01

    Results from epidemiological studies suggest that there is an association between periodontitis and prediabetes, however, causality is not known. The results from our previous studies suggest that induction of periodontitis leads to hyperinsulinemia glucose intolerance and insulin resistance, all hallmarks of prediabetes. However, global effects of periodontitis on critical organs in terms of metabolic alterations are unknown. We determined the metabolic effects of periodontitis on brain, liver, heart and plasma resulting from Porphyromonas gingivalis induced periodontitis in mice. Periodontitis was induced by oral application of the periodontal pathogen, Porphyromonas gingivalis for 22 weeks. Global untargeted biochemical profiles in samples from these organs/plasma were determined by liquid and gas chromatography/mass spectrometry and compared between controls and animals with periodontitis. Oral application of Porphyromonas gingivalis induced chronic periodontitis and hallmarks of prediabetes. The results of sample analyses indicated a number of changes in metabolic readouts, including changes in metabolites related to glucose and arginine metabolism, inflammation and redox homeostasis. Changes in biochemicals suggested subtle systemic effects related to periodontal disease, with increases in markers of inflammation and oxidative stress most prominent in the liver. Signs of changes in redox homeostasis were also seen in the brain and heart. Elevated bile acids in liver were suggestive of increased biosynthesis, which may reflect changes in liver function. Interestingly, signs of decreasing glucose availability were seen in the brain. In all three organs and plasma, there was a significant increase in the microbiome-derived bioactive metabolite 4-ethylphenylsulfate sulfate in animals with periodontitis. The results of metabolic profiling suggest that periodontitis/bacterial products alter metabolomic signatures of brain, heart, liver, and plasma in the

  5. 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

  6. 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.

  7. Metallothionein deficiency aggravates depleted uranium-induced nephrotoxicity.

    Science.gov (United States)

    Hao, Yuhui; Huang, Jiawei; Gu, Ying; Liu, Cong; Li, Hong; Liu, Jing; Ren, Jiong; Yang, Zhangyou; Peng, Shuangqing; Wang, Weidong; Li, Rong

    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 (10mg/kg, intraperitoneal injection) or an equivalent volume of saline. After 4days 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. PMID:26148447

  8. Effect of copper and copper binding protein on the CT attenuation value of liver. Experimental study in rats

    International Nuclear Information System (INIS)

    We analyzed the effect of copper and copper binding protein on CT attenuation value in a rat model. CT attenuation values of the liver were compared with hepatic copper content and grade of orcein-positive granules, which are thought to be a counterpart of polymerized metallothionein in lysosomes. The difference between hepatic copper and CT attenuation value was not statistically significant (R=0.056, p=0.96). CT value had a positive correlation with the grade of orcein-positive granules (Rho=0.755, p=0.0001). We concluded that the CT attenuation value of liver can be elevated by rich polymerized metallothionein (copper binding protein) in lysosomes. (author)

  9. 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.

  10. Anti-Inflammatory Property of Plantago major Leaf Extract Reduces the Inflammatory Reaction in Experimental Acetaminophen-Induced Liver Injury.

    Science.gov (United States)

    Hussan, Farida; Mansor, Adila Sofea; Hassan, Siti Nazihahasma; Tengku Nor Effendy Kamaruddin, Tg Nurul Tasnim; Budin, Siti Balkis; Othman, Faizah

    2015-01-01

    Hepatic injury induces inflammatory process and cell necrosis. Plantago major is traditionally used for various diseases. This study aimed to determine the anti-inflammatory property of P. major leaf extracts on inflammatory reaction following acetaminophen (APAP) hepatotoxicity. Thirty male Sprague-Dawley rats were divided into 5 groups, namely, normal control (C), APAP, aqueous (APAP + AQ), methanol (APAP + MT), and ethanol (APAP + ET) extract treated groups. All APAP groups received oral APAP (2 g/kg) at day 0. Then, 1000 mg/kg dose of P. major extracts was given for six days. The levels of liver transaminases were measured at day 1 and day 7 after APAP induction. At day 7, the blood and liver tissue were collected to determine plasma cytokines and tissue 11β-HSD type 1 enzyme. The in vitro anti-inflammatory activities of methanol, ethanol, and aqueous extracts were 26.74 ± 1.6%, 21.69 ± 2.81%, and 12.23 ± 3.15%, respectively. The ALT and AST levels were significantly higher in the APAP groups at day 1 whereas the enzyme levels of all groups showed no significant difference at day 7. The extracts treatment significantly reduced the proinflammatory cytokine levels and significantly increased the 11β-HSD type 1 enzyme activity (p major extracts attenuate the inflammatory reaction following APAP-induced liver injury. PMID:26300946

  11. Anti-Inflammatory Property of Plantago major Leaf Extract Reduces the Inflammatory Reaction in Experimental Acetaminophen-Induced Liver Injury

    Directory of Open Access Journals (Sweden)

    Farida Hussan

    2015-01-01

    Full Text Available Hepatic injury induces inflammatory process and cell necrosis. Plantago major is traditionally used for various diseases. This study aimed to determine the anti-inflammatory property of P. major leaf extracts on inflammatory reaction following acetaminophen (APAP hepatotoxicity. Thirty male Sprague-Dawley rats were divided into 5 groups, namely, normal control (C, APAP, aqueous (APAP + AQ, methanol (APAP + MT, and ethanol (APAP + ET extract treated groups. All APAP groups received oral APAP (2 g/kg at day 0. Then, 1000 mg/kg dose of P. major extracts was given for six days. The levels of liver transaminases were measured at day 1 and day 7 after APAP induction. At day 7, the blood and liver tissue were collected to determine plasma cytokines and tissue 11β-HSD type 1 enzyme. The in vitro anti-inflammatory activities of methanol, ethanol, and aqueous extracts were 26.74 ± 1.6%, 21.69 ± 2.81%, and 12.23 ± 3.15%, respectively. The ALT and AST levels were significantly higher in the APAP groups at day 1 whereas the enzyme levels of all groups showed no significant difference at day 7. The extracts treatment significantly reduced the proinflammatory cytokine levels and significantly increased the 11β-HSD type 1 enzyme activity (p<0.05. In conclusion, the P. major extracts attenuate the inflammatory reaction following APAP-induced liver injury.

  12. 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.

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

    Science.gov (United States)

    Poništ, Silvester; Mihálová, Danica; Nosáľ, Radomír; Harmatha, Juraj; Hrádková, Iveta; Šišková, Katarína; Bezáková, Lýdia

    2016-01-01

    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.

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

    Science.gov (United States)

    Pašková, Ľudmila; Kuncírová, Viera; Poništ, Silvester; Mihálová, Danica; Nosáľ, Radomír; Harmatha, Juraj; Hrádková, Iveta; Čavojský, Tomáš; Bilka, František; Šišková, Katarína; Paulíková, Ingrid; Bezáková, Lýdia; Bauerová, Katarína

    2016-01-01

    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. PMID:27556049

  15. 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...

  16. Inhibition of PAR-4 and P2Y12 receptor-mediated platelet activation produces distinct hepatic pathologies in experimental xenobiotic-induced cholestatic liver disease.

    Science.gov (United States)

    Joshi, Nikita; Kopec, Anna K; Ray, Jessica L; Luyendyk, James P

    2016-07-15

    Emerging evidence supports a protective effect of platelets in experimental cholestatic liver injury and cholangiofibrosis. Coagulation-mediated platelet activation has been shown to inhibit experimental chronic cholestatic liver necrosis and biliary fibrosis. This occurs through thrombin-mediated activation of protease activated receptor-4 (PAR-4) in mice. However, it is not known whether other pathways of platelet activation, such as adenosine diphosphate (ADP)-mediated receptor P2Y12 activation is also protective. We tested the hypothesis that inhibition of P2Y12-mediated platelet activation exacerbates hepatic injury and cholangiofibrosis, and examined the impact of P2Y12 inhibition in both the presence and absence of PAR-4. Treatment of wild-type mice with the P2Y12 receptor antagonist clopidogrel increased biliary hyperplasia and cholangiofibrosis in wild-type mice exposed to the xenobiotic alpha-naphthylisothiocyanate (ANIT) for 4 weeks compared to vehicle-treated mice exposed to ANIT. Interestingly, this effect of clopidogrel occurred without a corresponding increase in hepatocellular necrosis. Whereas biliary hyperplasia and cholangiofibrosis were increased in PAR-4(-/-) mice, clopidogrel treatment failed to further increase these pathologies in PAR-4(-/-) mice. The results indicate that inhibition of receptor P2Y12-mediated platelet activation exacerbates bile duct fibrosis in ANIT-exposed mice, independent of hepatocellular necrosis. Moreover, the lack of an added effect of clopidogrel administration on the exaggerated pathology in ANIT-exposed PAR-4(-/-) mice reinforces the prevailing importance of coagulation-mediated platelet activation in limiting this unique liver pathology. PMID:27475285

  17. 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

  18. Metallothionein deficiency aggravates depleted uranium-induced nephrotoxicity

    International Nuclear Information System (INIS)

    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

  19. Effect of copper and copper binding protein on CT attenuation value of the liver. Experimental study in rats

    International Nuclear Information System (INIS)

    We analyzed the effect of copper and copper binding protein on CT attenuation value in a rat model. Five LEC rats, which were thought to be rats with a form of Wilson's disease, and 28 Wistar rats were used in this study. Wistar rats were divided into 4 groups. Five Wistar rats were the control group. In 5 Wistar rats, the common bile duct was ligated. In 7 Wistar rats, after the common bile duct was ligated, cupric chloride solution (daily dose of 1.8-2.4 mg copper/kg) was intraperitoneally overloaded during a period of 32-60 days. High dose copper (cupric nitrinotriacetate, daily dose of 4 mg copper/kg) was given intraperitoneally in 11 Wistar rats during a period of 21-120 days. Hepatic copper was measured by atomic absorption spectrophotometry. CT attenuation values at non-enhanced CT of the liver were examined in all rats and compared with the hepatic copper content and the grade of orcein positive granules that is thought to be a counter-part of polymerized metallothionein in lysosome. The difference between hepatic copper and attenuation values at CT was not statistically significant (correlation coefficient=0.056, p=0.96). However, CT value has a strong positive correlation with the grade of orcein positive granules (Spearman's correlation coefficient Rho=0.755, Rho corrected for ties, 0.736, p=0.0001). CT value of the liver of LEC rats did not differ from that of normal control rats. We concluded that CT attenuation values of the liver can be elevated by rich polymerized metallothionein (copper binding protein) in lysosome and has a negative correlation with hepatic copper content. (author) 50 refs

  20. 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

  1. 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.

  2. 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.

  3. 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. PMID:27663368

  4. Progression of Liver Disease

    Science.gov (United States)

    ... Browse Related Terms Progression of Liver Disease , Family History of Liver Disease , Liver Wellness , Liver Failure , Liver Biopsy Home > Your Liver > Liver Disease Information > The Progression ...

  5. 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

  6. 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

  7. 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.

  8. 当飞利肝宁胶囊预防非酒精性脂肪性肝病大鼠肝纤维化%Dangfei Liganning capsules prevent liver fibrosis in experimental rat of nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    宋海燕; 刘洋; 毛志敏; 徐汉辰; 杨丽丽; 柳涛; 季光

    2013-01-01

    Objective:To study the effect of Dangfei Liganning capsules on liver fibrosis in nonalcoholic fatty liver disease (NAFLD) rats.Methods:Thirty male Wistar rats were randomly divided into normal group,model group and treatment group.The rats of normal group were fed with a standard diet,while those of model and treatment groups with high-fat diet,and the rats for treatment were gastrically perfused with Dangfei Liganning capsules.After 8 weeks,the rats of model and treatment groups were intraperitoneally injected with low dose of CCl4.Forty-eight hours later,the experimental rats were sacrificed and their livers were frozen or fixed for future use.The liver tissue slides were stained with Sirius red and observed through microscope.Hepatic levels of plasminogen activator inhibitor-1 (PAI-1),transforming growth factor beta 1 (TGF-β1),alpha smooth muscle actin (αt-SMA),collagen type I,alpha1 (COL1A1) and β-actin were measured by quantitative RT-PCR and Western blot.Results:Compared with normal group,the liver tissues of model rat showed extensive lobular hepatic steatosis,companied with mild peri-sinusoidal fibrosis in zone 3 area.No obvious collagen deposition was observed in the liver of treating rats.Dramatically increased mRNA level of PAI-1,TGF-β1,α-SMA and COL1A1,as well as the protein expressing level of PAI-1,were determined in the liver tissues of model rats (P < 0.05),while in the treatment group,the expression of these pro-fibrogenesis genes were down-regulated obviously (P <0.05).Conclusion:Dangfei Liganning capsules could prevent liver fibrosis of NAFLD rats.The underlying mechanism might partially lie in inhibiting the activation of hepatic stellate cells and collagen production,as well as promoting the degradation of extracellular matrix,through regulating the expression of TGF-β1 and PAI-l in NAFLD pathophysiology.%目的:研究当飞利肝宁胶囊对大鼠非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)肝纤维化的

  9. 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. PMID:27439970

  10. EFFECT OF PIGEON ORIGIN NEWCASTLE DISEASE VIRUS ON VARIOUS LIVER ENZYMES AND ASSOCIATED PATHOLOGICAL CHANGES IN EXPERIMENTALLY INFECTED PIGEONS

    Directory of Open Access Journals (Sweden)

    I. MUSHTAQ, F. RIZVI AND M. S. ULLAH

    2006-10-01

    Full Text Available Newcastle disease virus (NDV was isolated from a field outbreak in pigeons. The virus was characterized by haemagglutination test (HA and confirmed by haemagglutination inhibition test (HAI. The pathotyping was done by mean death time (MDT, intracerebral pathogenicity index (ICPI and intravenous pathogenicity index (IVPI. The ELD50 of the velogenic strain was 10-4.66/0.1 ml. Thirty-nine pigeons were randomly divided into three equal groups. Pigeons of one group were vaccinated with ND vaccine (LaSota strain intraocularly after 14 days of procurement, while the other two groups served as vaccinated and non-vaccinated controls. Birds of these two groups were challenged with velogenic strain of field isolate of NDV 7 days post-vaccination. Birds were kept under observation for 15 days post-challenge. Haemorrhages and congestion were observed in trachea, lungs, liver, proventriculus and intestine of pigeons infected with NDV. Concentrations of AST, ALT and ALP did not differ among pigeons of the three groups.

  11. EXPERIMENTAL STUDY ON ISCHEMIA AND REPERFUSION INJURY OF RAT LIVER AND EFFECTS OF LIGUSTRAZINE AND SALVIA COMPOUND

    Institute of Scientific and Technical Information of China (English)

    武卫国; 裘法祖

    1994-01-01

    The present study was to investigate changes of free radicals in the whole rat liver,changes of ATP levels of hepatic cells,ultrastructural changes in hepatic tissue during ischemia and reperfusion in rats and the effects of ligustrazine and salvia compound.The results indicated that:1)the free radical levels increased by 8.3fold and 9.0-fold in the groups with 30 and 60 min ischemia after 40min reperfusion ,as compared with the group with ischemia only(P<0.01,P<0.01,respectively).2)The levels of ATP returned to normal in the group with 30min ischemia after reperfusion for 40min and 3d ,remained low in the group with 90min ischemia and fell again after a mild increase in the group with 60min ischemia.3)The hepatic and endothelial cell damage after ischemia became more severe after reperfusion,as revealed by electron microscopy.The presenet study also showed that ligustrazine and salvia compound have protective effects against reperfusion injury.They can be used to scavenge free radicals,improve hepatic microcirculation and alleviate hepatic and endothelial cell damage.

  12. Immune mechanisms in acetaminophen-induced acute liver failure.

    Science.gov (United States)

    Krenkel, Oliver; Mossanen, Jana C; Tacke, Frank

    2014-12-01

    An overdose of acetaminophen (N-acetyl-p-aminophenol, APAP), also termed paracetamol, can cause severe liver damage, ultimately leading to acute liver failure (ALF) with the need of liver transplantation. APAP is rapidly taken up from the intestine and metabolized in hepatocytes. A small fraction of the metabolized APAP forms cytotoxic mitochondrial protein adducts, leading to hepatocyte necrosis. The course of disease is not only critically influenced by dose of APAP and the initial hepatocyte damage, but also by the inflammatory response following acetaminophen-induced liver injury (AILI). As revealed by mouse models of AILI and corresponding translational studies in ALF patients, necrotic hepatocytes release danger-associated-molecular patterns (DAMPs), which are recognized by resident hepatic macrophages, Kupffer cell (KC), and neutrophils, leading to the activation of these cells. Activated hepatic macrophages release various proinflammatory cytokines, such as TNF-α or IL-1β, as well as chemokines (e.g., CCL2) thereby further enhancing inflammation and increasing the influx of immune cells, like bone-marrow derived monocytes and neutrophils. Monocytes are mainly recruited via their receptor CCR2 and aggravate inflammation. Infiltrating monocytes, however, can mature into monocyte-derived macrophages (MoMF), which are, in cooperation with neutrophils, also involved in the resolution of inflammation. Besides macrophages and neutrophils, distinct lymphocyte populations, especially γδ T cells, are also linked to the inflammatory response following an APAP overdose. Natural killer (NK), natural killer T (NKT) and T cells possibly further perpetuate inflammation in AILI. Understanding the complex interplay of immune cell subsets in experimental models and defining their functional involvement in disease progression is essential to identify novel therapeutic targets for human disease. PMID:25568858

  13. 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.

  14. 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 ...

  15. 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

  16. Liver Panel

    Science.gov (United States)

    ... liver damage. Alpha-feto protein (AFP) – associated with regeneration or proliferation of liver cell Autoimmune antibodies (e. ... the body – such as in the skeletal muscles, pancreas, or heart. It may also indicate early liver ...

  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. Liver Diseases

    Science.gov (United States)

    ... remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis A, ... the skin, can be one sign of liver disease. Cancer can affect the liver. You could also ...

  19. 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

  20. Optimal Transthoracic Targeting of Liver Tumors Using Dual-mode Ultrasound Arrays: A numerical and experimental study

    Science.gov (United States)

    Casper, Andrew; Ballard, John; Ebbini, Emad

    2010-03-01

    The targets of therapeutic ultrasound are often located behind strongly scattering objects and layered tissue. These inhomogeneities can degrade the intended foci and misdirect acoustic energy causing unwanted hot spots or failure to meet the therapeutic endpoint at the target. We have previously shown the capabilities of dual-mode ultrasound arrays (DMUAs) in imaging strongly scattering objects in the path of the HIFU beam and, consequently, refocusing the beam to optimize the power deposition at the target while minimizing direct exposure to the obstacles. This capability may be a key to successful transthoracic targeting of abdominal tumors. We have experimentally verified the efficacy of this approach in improving the quality of the therapeutic focus and minimizing collateral damage to critical tissue structures in the path of the HIFU beam. In order to study the phenomena associated with transthoracic focusing more thoroughly, we have developed a finite-difference time-domain simulation capable of characterizing the transient propagation of the therapeutic beam through inhomogeneous, attenuating media. This simulation is shown to provide the necessary information for aberration correction of deep seated foci as well as control over the acoustic field at select points. In addition, the FDTD simulation allows for computation of the temperature rise throughout the therapeutic region as governed by the transient bioheat transfer equation. We have validated the predictive abilities of our simulation with hydrophone measurements as well as thermocouple readings from within tissue mimicking phantoms. The experimental validation of the simulation model allows for its use as a key component in treatment planning of thermal therapy using HIFU. Experimental and simulation results demonstrating the role of the advantages of incorporation of the computational model in optimizing the quality of HIFU beams will be presented and discussed.

  1. SUB CHRONIC TOXICITY TEST FROM ALKOHOL EXTRACT PALIASA LEAVES (Kleinhovia Hospita Linn TO HEPAR/LIVER AND KIDNEY OF EXPERIMENTAL MICE

    Directory of Open Access Journals (Sweden)

    Raflizar Raflizar

    2012-09-01

    Full Text Available Paliasa leaves used to be a traditional medicine for hepatic/ lever desease, so need to maintain the secure & health from the user of this medicine, the aim of the research is to find the dava of ub chronic toxicity from 70% alcohol extract paliasa leaves for experimental mice. The research use amount 30 of 40 months white male mice wistar strain, which have weight in average (SD about 208,75 ±17,47 gr. The extract was given by oral through the spuit for 12 weeks ( 3 months for every mice. After that, all of mice had been killed by ether liquid, andfor histology examination, the blood had been taken from the mice's heart, liver & kidney. The research had been conduct with completed random design includes 5 treatments & 6 repeats. Each treatment includes give the mice aquades with dosage 0 mg/kg body weight (control for 1st group paliasa leaves extract with dosage 250 mg/kg body weight for 2nd group, 3rd group with dosage 500 mg/kg body weight, 4th group with dosage 750 mb/kg body weight & for 5th group with dosage 1000 mg/kg body weight. SGOT, SGPT, Bilirubin direct& indirect, creatinin, ureum kidney & liver cell destruction had been measured from all of groups. The result shows that from eight parameters, in statistically, there are no significant differences between each treatment. The conclution is paliasa leaves extract still save in every treatment dosage. Key words : Toxicity, Electract Paliasa Leaves, Kidney

  2. An experimental study of triple split-liver transplantation in dogs%“一肝三受”动物实验的可行性

    Institute of Scientific and Technical Information of China (English)

    周峻; 明安晓; 李胜利; 王海斌; 王政; 李龙; 陈芳林; 崔龙; 谢华伟; 侯文英; 张金山; 刘树立

    2012-01-01

    -tion of these two parenchymal bridges. The portal vein was split into three branches. The common bile duct was formed by the union of three hepatic ducts-the left, middle and right hepatic ducts. The hepatic vein consisted of the left, median and right hepatic veins. Anatomical variations in the hepatic arteries could be found. Among three recipient groups, the operation time, anhepatic time and blood loss did not show significant dif-ferences (P > 0.05), but the mean recipient weight, liver graft weight, and GRWR differed significantly (all P 0.05), but the mean recipient weight, liver graft weight, and GRWR differed significantly (all P < 0.01). In the three groups, none of the recipients died during surgery. Once the hepatic vein and the portal vein were anastomosed and declamped, the implanted liver regained its color soon and its appearance returned to normal following arterial revascularization. There was no statistical difference in survival duration among the three groups (128.3 h ?48.5 h vs 102.7 h ?59.8 h vs 98.7 h ?46.8 h, P = 0.234). Ascites and liver necrosis were not found at autopsy. Bile was present in the bile duct and all anastomoses were patent. CONCLUSION: Our experimental results indicate that the whole liver of a big dog can be split into three parts, every one of which can be transplanted to a small recipient as an independent allograft.

  3. 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.

  4. 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.)

  5. MR T1ρ as an imaging biomarker for monitoring liver injury progression and regression: an experimental study in rats with carbon tetrachloride intoxication

    International Nuclear Information System (INIS)

    Recently it was shown that the magnetic resonance imaging (MRI) T1ρ value increased with the severity of liver fibrosis in rats with bile duct ligation. Using a rat carbon tetrachloride (CCl4) liver injury model, this study further investigated the merit of T1ρ relaxation for liver fibrosis evaluation. Male Sprague-Dawley rats received intraperitoneal injection of 2 ml/kg CCl4 twice weekly for up to 6 weeks. Then CCl4 was withdrawn and the animals were allowed to recover. Liver T1ρ 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 CCl4 injection, and they were also examined at 1 week and 4 weeks post CCl4 withdrawal. Liver histology was also sampled at these time points. Liver T1ρ values increased slightly, though significantly, on day 2, and then increased further and were highest at week 6 post CCl4 insults. The relative liver signal intensity change on T2-weighted images followed a different time course compared with that of T1ρ. Liver T1ρ values decreased upon the withdrawal of the CCl4 insult. Histology confirmed the animals had typical CCl4 liver injury and fibrosis progression and regression processes. MR T1ρ imaging can monitor CCl4-induced liver injury and fibrosis. (orig.)

  6. 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…

  7. 33 CFR 20.1315 - Submission of prior records and evidence in aggravation or mitigation.

    Science.gov (United States)

    2010-07-01

    ... PROCEEDINGS OF THE COAST GUARD Supplementary Evidentiary Rules for Suspension and Revocation Hearings § 20... aware. The Coast Guard representative may offer evidence and argument in aggravation of any charge proved. The respondent may offer evidence of, and argument on, prior maritime service, including both...

  8. Street Life: Aggravated and Sexual Assaults among Homeless and Runaway Adolescents.

    Science.gov (United States)

    Terrell, Nathanial Eugene

    1997-01-01

    Examines aggravated and sexual assaults among 240 runaway and homeless adolescents (RHAs) in Des Moines (Iowa). Results suggest RHAs are at risk of life-threatening situations on the streets due to aggressive and abusive parents. Additionally, street life situations have significant impacts on the probability that RHAs will be victims of…

  9. Experimental study on L-[1-13C] phenylalanine breath test for quantitative assessment of liver function with animal

    International Nuclear Information System (INIS)

    Objective: Using a small animal breath test model we designed and L-[1-13C] phenylalanine breath test (13C-PheBT) of rats, the authors investigated its feasibility and validity and determined effective parameter of the test. Methods: Twenty male Sprague-Dawley (SD) weighting 280-290 g rats randomized into two groups acute hepatitis rats (n=10) and control rats (n=10). Hepatitis was induced by carbon tetrachloride (CCl4) olive oil administration through intragastric gavage. PheBT was assisted by small mechanical ventilator improved and air samples were collected discontinuously, 20 mg/kg body weight L-[1-13C] phenylalanine (13C-Phe) was administered intravenously. Twenty-nine breath samples were taken before and different intervals within sixty minutes after administration. 13Cenrichment was measured by isotope ratio mass spectrometer. Results: All time phase curves of 13C enrichment in rat breath reached a peak almost at 2 min after the intravenous administration of 13C-Phe. The PheBT parameters, 13C excretion rate constant (PheBT-K), of CCl4 hepatitis rats were significantly lower than that of normal control rats [(2.45 ± 0.25) x 10-2 min-1 vs (2.98 ± 0.19) x 10-2 min-1, t = 5.40, P13C fast phase disposition constant did not statistically differ between the two groups (t=0.58, P>0.05). PheBT-K had significant negative cor-relation with serum ALT, AKP, TBA and total bilirum TBIL (the correlation coefficient r is -0.74, -0.73, -0.82 and -0.67 respectively, P0.05). Conclusions: It was indicated that the small animal breath test model we designed was a virtual tool to use in experimental study on breath test and PheBT-K was a sensitive index. (authors)

  10. 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.

  11. 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.

  12. 5 CFR 890.1016 - Aggravating and mitigating factors used to determine the length of permissive debarments.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Aggravating and mitigating factors used....1016 Aggravating and mitigating factors used to determine the length of permissive debarments. (a..., or impede official inquiries into the wrongful conduct underlying the debarment. (b)...

  13. 77 FR 26703 - Inflation Adjustment of the Aggravated Maximum Civil Monetary Penalty for a Violation of a...

    Science.gov (United States)

    2012-05-07

    ... Aggravated Maximum Civil Monetary Penalty for a Violation of a Federal Railroad Safety Law or Federal..., FRA published a final rule, pursuant to the Federal Civil Penalties Inflation Adjustment Act of 1990, which increased the aggravated maximum civil monetary penalty that the agency will apply when...

  14. Vascular Endothelial Growth Factor-Receptor 1 Inhibition Aggravates Diabetic Nephropathy through eNOS Signaling Pathway in db/db Mice

    OpenAIRE

    Keun Suk Yang; Ji Hee Lim; Tae Woo Kim; Min Young Kim; Yaeni Kim; Sungjin Chung; Seok Joon Shin; Beom Soon Choi; Hyung Wook Kim; Yong-Soo Kim; Yoon Sik Chang; Hye Won Kim; Cheol Whee Park

    2014-01-01

    The manipulation of vascular endothelial growth factor (VEGF)-receptors (VEGFRs) in diabetic nephropathy is as controversial as issue as ever. It is known to be VEGF-A and VEGFR2 that regulate most of the cellular actions of VEGF in experimental diabetic nephropathy. On the other hand, such factors as VEGF-A, -B and placenta growth factor bind to VEGFR1 with high affinity. Such notion instigated us to investigate on whether selective VEGFR1 inhibition with GNQWFI hexamer aggravates the progre...

  15. 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

  16. Liver Cancer Stem Cells

    OpenAIRE

    Sameh Mikhail; Aiwu Ruth He

    2011-01-01

    Hepatocellular carcinoma is the most common primary malignancy of the liver in adults. It is also the fifth most common solid cancer worldwide and the third leading cause of cancer-related death. Recent research supports that liver cancer is a disease of adult stem cells. From the models of experimental hepatocarcinogenesis, there may be at least three distinct cell lineages with progenitor properties susceptible to neoplastic transformation. Identification of specific cell surface markers fo...

  17. Liver transplant

    Science.gov (United States)

    ... transplant - series References Keefe EB. Hepatic failure and liver transplantation. In: Goldman L, Schafer AI, eds. Goldman's Cecil ... Elsevier; 2011:chap 157. Martin P, Rosen HR. Liver transplantation. In: Feldman M, Friedman LS, Brandt LJ, eds. ...

  18. Inhibition of catecholamine degradation ameliorates while chemical sympathectomy aggravates the severity of acute Friend retrovirus infection in mice.

    Science.gov (United States)

    Bloemker, Dominique; Mollerus, Sina; Gibbert, Kathrin; Dittmer, Ulf; del Rey, Adriana; Schedlowski, Manfred; Engler, Harald

    2016-05-01

    Several lines of evidence indicate that the sympathetic nervous system (SNS) might be involved in the pathogenesis and progression of retroviral infections. However, experimental data are scarce and findings inconsistent. Here, we investigated the role of the SNS during acute infection with Friend virus (FV), a pathogenic murine retrovirus that causes polyclonal proliferation of erythroid precursor cells and splenomegaly in adult mice. Experimental animals were infected with FV complex, and viral load, spleen weight, and splenic noradrenaline (NA) concentration was analyzed until 25 days post infection. Results show that FV infection caused a massive but transient depletion in splenic NA during the acute phase of the disease. At the peak of the virus-induced splenomegaly, splenic NA concentration was reduced by about 90% compared to naïve uninfected mice. Concurrently, expression of the catecholamine degrading enzymes monoamine oxidase A (MAO-A) and catechol-O-methyltransferase (COMT) was significantly upregulated in immune cells of the spleen. Pharmacological inhibition of MAO-A and COMT by the selective inhibitors clorgyline and 3,5-dinitrocatechol, respectively, efficiently blocked NA degradation and significantly reduced viral load and virus-induced splenomegaly. In contrast, chemical sympathectomy prior to FV inoculation aggravated the acute infection and extended the duration of the disease. Together these findings demonstrate that catecholamine availability at the site of viral replication is an important factor affecting the course of retroviral infections. PMID:26880342

  19. Postoperative neurological aggravation after anesthesia with sevoflurane in a patient with xeroderma pigmentosum: a case report

    OpenAIRE

    Fjouji, Salaheddine; Bensghir, Mustapha; Yafat, Bahija; Bouhabba, Najib; Boutayeb, Elhoucine; Azendour, Hicham; Kamili, Nordine Drissi

    2013-01-01

    Introduction Xeroderma pigmentosum is a rare autosomal recessive disease that causes changes in skin pigmentation, precancerous lesions and neurological abnormalities. It is a defect in the nucleotide excision repair mechanism. It has been reported that volatile anesthetics has a possible genotoxic side effect and deranged nucleotide excision repair in cells obtained from a patient with xeroderma pigmentosum. We report an unusual case of postoperative neurological aggravation in a patient wit...

  20. 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.

  1. Aggravated stuttering following subthalamic deep brain stimulation in Parkinson's disease - two cases

    Directory of Open Access Journals (Sweden)

    Dietrichs Espen

    2011-04-01

    Full Text Available Abstract Stuttering is a speech disorder with disruption of verbal fluency which is occasionally present in patients with Parkinson's disease (PD. Long-term medical management of PD is frequently complicated by fluctuating motor functions and dyskinesias. High-frequency deep brain stimulation (DBS of the subthalamic nucleus (STN is an effective treatment of motor fluctuations and is the most common surgical procedure in PD. Here we report the re-occurrence and aggravation of stuttering following STN-DBS in two male patients treated for advanced PD. In both patients the speech fluency improved considerably when the neurostimulator was turned off, indicating that stuttering aggravation was related to neurostimulation of the STN itself, its afferent or efferent projections and/or to structures localized in the immediate proximity. This report supports previous studies demonstrating that lesions of the basal ganglia-thalamocortical motor circuit, including the STN, is involved in the development of stuttering. In advanced PD STN-DBS is generally an effective and safe treatment. However, patients with PD and stuttering should be informed about the risk of aggravated symptoms following surgical therapy.

  2. 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...

  3. Effect of dopamine-related drugs on duodenal ulcer induced by cysteamine or propionitrile: prevention and aggravation may not be mediated by gastrointestinal secretory changes in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Gallagher, G.; Brown, A.; Szabo, S.

    1987-03-01

    Dose- and time-response studies have been performed with dopamine agonists and antagonists using the cysteamine and propionitrile duodenal ulcer models in the rat. The experiments demonstrate that the chemically induced duodenal ulcer is prevented by bromocriptine, lergotrile and reduced by apomorphine or L-dopa. Aggravation of cysteamine-induced duodenal ulcer was seen especially after (-)-butaclamol, (-)-sulpiride, haloperidol and, less effectively, after other dopaminergic antagonists. The duodenal antiulcerogenic action of dopamine agonists was more prominent after chronic administration than after a single dose, whereas the opposite was found concerning the proulcerogenic effect of dopamine antagonists. In the chronic gastric fistula rat, both the antiulcerogens bromocriptine or lergotrile and the proulcerogens haloperidol, pimozide or (-)-N-(2-chlorethyl)-norapomorphine decreased the cysteamine- or propionitrile-induced gastric secretion. No correlation was apparent between the influence of these drugs on duodenal ulcer development and gastric and duodenal (pancreatic/biliary) secretions. In the chronic duodenal fistula rat, decreased acid content was measured in the proximal duodenum after haloperidol, and diminished duodenal pepsin exposure was recorded after bromocriptine. Furthermore, the aggravation by dopamine antagonists of experimental duodenal ulcer probably involves a peripheral component. The site of dopamine receptors and physiologic effects which modulate experimental duodenal ulcer remain to be identified, but their elucidation may prove to be an important element in the pathogenesis and treatment of duodenal ulcer.

  4. 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.

  5. The use of synthetic analogues of Arg-Gly-Asp (RGD) and soluble receptor of tumor necrosis factor to prevent acute and chronic experimental liver injury.

    Science.gov (United States)

    Bruck, R; Hershkoviz, R; Lider, O; Shirin, H; Aeed, H; Halpern, Z

    1997-01-01

    In chronic viral hepatitis, autoimmune hepatitis, and some chronic cholestatic liver diseases, T-lymphocytes serve as effector cells of the immunostimulatory processes. Cellular interactions of immune cells with extracellular matrix (ECM) components are regulated primarily via the beta 1 subfamily of integrin receptors. The target epitope of several such integrin receptors is the Arg-Gly-Asp (RGD) sequence, a cell adhesion motif shared by several matrix-associated adhesive glycoproteins. We review the use of synthetic nonpeptidic analogues of RGD and of soluble receptor of tumor necrosis factor (TNF)-alpha in the prevention of immune-mediated, concanavalin A-induced liver damage in mice and of RGD analogues in inhibiting the development of liver cirrhosis in rats. The concanavalin A-induced elevation of serum transaminases and TNF-alpha, and the infiltration of liver tissue by inflammatory cells, were inhibited by pretreatment of the mice with the synthetic RGD mimetics and soluble TNF receptor. In rats, the progression of thioacetamide-induced liver cirrhosis was markedly inhibited by the coadministration of the RGD mimetic SF-6,5. The compounds described here may be examined therapeutically for pathological conditions in the liver, manifested as necroinflammation, cholestasis and fibrosis. PMID:9626759

  6. 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

  7. Aggravation of post-ischemic liver injury by overexpression of insulin-like growth factor binding protein 3

    OpenAIRE

    Lu Zhou; Hyoung-Won Koh; Ui-Jin Bae; Byung-Hyun Park

    2015-01-01

    Insulin-like growth factor-1 (IGF-1) is known to inhibit reperfusion-induced apoptosis. IGF-binding protein-3 (IGFBP-3) is the major circulating carrier protein for IGF-1 and induces apoptosis. In this study, we determined if IGFBP-3 was important in the hepatic response to I/R. To deliver IGFBP-3, we used an adenovirus containing IGFBP-3 cDNA (AdIGFBP-3) or an IGFBP-3 mutant devoid of IGF binding affinity but retaining IGFBP-3 receptor binding ability (AdIGFBP-3GGG). Mice subjected to I/R in...

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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; Almeida, Adilson José de; Pelajo-Machado, Marcelo; Castro, Tatiana Xavier de; Nascimento, Jussara Pereira do; Brown, Kevin E; Pinto, Marcelo Alves

    2016-04-01

    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

  14. Effects of intra-arterial chemotherapy with a new lipophilic anticancer agent, estradiol-chlorambucil (KM2210), dissolved in lipiodol on experimental liver tumor in rats

    International Nuclear Information System (INIS)

    Anticancer effects and biodistribution of a new lipophilic anticancer agent, estradiol-chlorambucil (KM2210), dissolved in lipiodol (LPD) were investigated as an intra-arterial chemotherapy (IAC) on Walker 256 carcinosarcoma grown in the liver of 136 Wistar rats. All rats treated with KM2210 (10 mg)-LPD survived for 90 days after administration, whereas none of the rats with LPD alone were alive for more than 19 days. Histological examination revealed that there was no viable tumor cell in the encapsulated necrotic tumor at 21 days after administration. There was no significant liver dysfunction or leukopenia due to KM2210. The biodistribution study using [14C, 3H]KM2210-LPD solution showed that KM2210 accumulated selectively in tumor and that the tumor-to-normal-liver and tumor-to-blood ratios were 10 and 1,000, respectively, at 21 days after administration. These results suggest that KM2210 has potential clinical application in the treatment of human liver cancer

  15. Evaluation of the role of laser bio stimulation on skin and liver of gamma-irradiated mice

    International Nuclear Information System (INIS)

    Low level laser therapy (LLLT) is used in different medical fields due to its therapeutic effects on reparative processes, pain relief and bio stimulation (Castro-e-silva et al., 2003). The present study aimed at evaluating the therapeutic efficacy of He-Ne laser in stimulating the reparative processes after whole body irradiation of mice using a sublethal dose (5 Gy) of gamma rays. Two vital organs were studied, a radio-sensitive one (the skin) as well as a relatively radio-resistant one (the liver) . During the course of the present work, some biochemical parameters as well as histopathological changes in the skin and liver tissues induced by whole body gamma ionizing radiation were studied. Female mice (240) were used and divided into 6 groups and laser therapy was carried out using a computerized scanner emitting He-Ne(C W) with a wavelength of 632.8 nm and the fluence was 5 j/cm2. Experimental investigation have been carried out along two main lines: Biochemical investigations for the assessment of serum transferases and histopathological assessment of liver and skin biopsy.On the basis of the current results it could be concluded that mice exposed to whole body gamma irradiation either by the US of the shot or the fractionated sublethal dose suffered an aggravated histopathological changes in the skin and liver tissues which were associated with certain biochemical disturbances of the liver function testes. These undesirable alterations were ameliorated by the early treatment of mice by He -Ne laser immediately post exposure before being irreversibly damaged

  16. 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.

  17. 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.

  18. Early atherosclerosis aggravates renal microvascular loss and fibrosis in swine renal artery stenosis.

    Science.gov (United States)

    Sun, Dong; Eirin, Alfonso; Ebrahimi, Behzad; Textor, Stephen C; Lerman, Amir; Lerman, Lilach O

    2016-04-01

    Renal function in patients with atherosclerosis and renal artery stenosis (ARAS) deteriorates more frequently than in nonatherosclerotic RAS. We hypothesized that ARAS aggravates stenotic-kidney micro vascular loss compared to RAS. Domestic pigs were randomized to normal, RAS, and ARAS (RAS fed a high-cholesterol diet) groups (n = 7 each). Ten weeks later stenotic-kidney oxygenation, renal blood flow, and glomerular filtration rate (GFR) were evaluated in vivo, and micro vascular density by micro-computed tomography. Blood pressure in both RAS and ARAS was elevated; and stenotic-kidney renal blood flow and GFR similarly decreased. RAS decreased the density of small-size cortical microvessels (sized microvessels (200-300 μm). Cortical hypoxia and interstitial fibrosis increased in both RAS and ARAS but correlated inversely with micro vascular density only in RAS. Atherosclerosis aggravates loss of stenotic-kidney microvessels, yet additional determinants likely contribute to cortical hypoxia and fibrosis in swine ARAS. PMID:26879682

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. Oral Candida as an aggravating factor of mucositis Induced by radiotherapy

    International Nuclear Information System (INIS)

    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)

  4. Heterotopic Auxiliary Liver Transplantation with Portal Flow

    OpenAIRE

    Laureano Lorente; Jaime Arias; Maria Angeles Aller; José Ignacio Ispizua; José Rodriguez; Hipólito Durán

    1990-01-01

    One of the causes of auxiliary liver transplantation failure is the inter-liver competition between the host liver and the graft for the hepatotrophic factors of the portal blood. We have developed an experimental model of heterotopic partial (30%) liver isotransplant using Wistar rats so as to study this competition. Splenoportography and dissection demonstrate the existence of collateral circulation. The collaterals at 90 days post-transplant (PT) consisted of veins from the portal vein to ...

  5. 中国原发性肝癌的临床和实验研究%Clinical and Experimental Research of Primary Liver Cancer in China

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ Primary liver cancer (PLC) is one of the most commonneoplasms and the second cancer-related cause ofdeath in China, respresenting a major health problem. InChina, PLC resulted in 20.40 deaths per 100 000 per year,with 19.98 per 100000 in cities and 23.59 per 100 000 inrural areas. Of all the newly enrolled PLC cases in the worldeach year, about 43% are found in the mainland of China[1

  6. Effects of combined liver and udder biopsying on the acute phase response of dairy cows with experimentally induced E. coli mastitis

    DEFF Research Database (Denmark)

    Khatun, Momena; Sørensen, Peter; Ingvartsen, Klaus Lønne;

    2013-01-01

    A minimally invasive biopsy technique was evaluated for udder tissue collection in dairy cows with Escherichia coli mastitis. Meanwhile, the effect of taking repeated liver and udder biopsies on the systemic and local acute phase response (APR) of the dairy cows was investigated during the disease...... the systemic and local APR in dairy cows during E. coli mastitis, if the timing of biopsying and other types of sampling is planned accordingly...

  7. [Activity of key enzymes of heme metabolism and cytochrome P-450 content in the rat liver in experimental rhabdomyolysis and hemolytic anemia].

    Science.gov (United States)

    Kaliman, P A; Inshina, N N; Strel'chenko, E V

    2003-01-01

    The 5-aminolevulinate synthase, heme oxygenase, tryptophan-2,3-dioxygenase activities, the content of total heme and cytochrome P-450 content in the rat liver and absorption spectrum of blood serum in Soret region under glycerol model of rhabdomiolisis and hemolytic anemia caused by single phenylhydrazine injection have been investigated. The glycerol injection caused a considerable accumulation of heme-containing products in the serum and the increase of the total heme content, holoenzyme, total activity and heme saturation of tryptophan-2,3-dioxygenase, as well as the increase of the 5-aminolevulinate synthase and heme oxygenase activities in the liver during the first hours of its action and the decrease of cytochrome P-450 content in 24 h. Administration of phenylhydrazine lead to the increasing of hemolysis products content in blood serum too, although it was less expressed. The phenylhydrazine injection caused the increase of activities of 5-aminolevulinate synthase, holoenzyme, total activity and heme saturation of tryptophan-2,3-dioxygenase, as well as decrease of cytochrome P-450 content in the rat liver in 2 h. The increase of the total heme content and heme oxygenase activity has been observed in 24 h. The effect of heme arrival from the blood stream, as well as a direct influence of glycerol and phenylhydrazine on the investigated parameters are discussed. PMID:14577161

  8. Liver spots

    Science.gov (United States)

    Sun-induced skin changes - liver spots; Senile or solar lentigines; Skin spots - aging; Age spots ... your skin by using skin bleaching lotions or creams. Most bleaching lotions use hydroquinone. This medicine is ...

  9. Liver Facts

    Science.gov (United States)

    ... idiopapathic) Liver tumors Biliary atresia Was this information helpful? E-mail us with feedback or questions. Reference ... or other discrepancies. Share this: Was this information helpful? Related topics Find transplant centers specializing in certain ...

  10. Heme oxygenase-1 protects donor livers from ischemia/reperfusion injury:The role of Kupffer cells

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To examine whether heme oxygenase (HO)-1 overexpression would exert direct or indirect effects on Kupffer cells activation, which lead to aggravation of reperfusion injury.METHODS: Donors were pretreated with cobalt protoporphyrin (CoPP) or zinc protoporphyrin (ZnPP), HO-1 inducer and antagonist, respectively. Livers were stored at 4℃ for 24 h before transplantation. Kupffer cells were isolated and cultured for 6 h after liver reperfusion.RESULTS: Postoperatively, serum transaminases were significantly ...

  11. 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

  12. 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)

    Yun-ru Li; Feng-xin Chen; Xue-fei Duan; Xue-song Gao; Xiao-ling Fan

    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.

  13. 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

  14. 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...

  15. Formation of structures in nonlinear media and nonequilibrium thermodynamics of aggravation regimes

    International Nuclear Information System (INIS)

    In a medium, the description of which includes quasilinear transport equations (the thermal conductivity, conductivity and viscosity coefficients depend on temperature, density and magnetic field), the effect of nonlinear bulk heat sources, under specific conditions, generates strongly nonequilibrium processes, the so-called regimes with aggravation. They can cause heat localization and magnetic field phenomena on certain space scales or in certain sections of the mass in a compressible medium. This results in different spatial distribution of the quantities indicated, i.e., development of different types of structures in the medium. The work, on the basis of consideration of the quasilinear thermal conductivity equation with nonlinear bulk heat sources, found the characteristics of the strongly nonequilibrium thermodynamics which cause such a complication of organization of the medium. 88 references

  16. Is Behavioral Regulation in Children With ADHD Aggravated by Comorbid Anxiety Disorder?

    DEFF Research Database (Denmark)

    Sørensen, Lin; Plessen, Kerstin J; Nicholas, Jude;

    2010-01-01

    Background: The present study investigated the impact of coexisting anxiety disorder in children with ADHD on their ability to regulate behavior. Method: Parent reports on the Behavior Rating Inventory of Executive Function (BRIEF) in a comorbid group of children with ADHD and anxiety (n = 11) were...... compared to BRIEF reports in a group of children with a "pure" ADHD (n = 23), a "pure" anxiety (n = 24) and a group without any diagnosis (n = 104) in a 2 (ADHD vs. no ADHD) x 2 (anxiety vs. no anxiety) design. Results: The children with ADHD and anxiety disorder scored significantly higher on the Inhibit...... children is aggravated by comorbid anxiety. (J. of Att. Dis. 2010; XX(X) 1-XX)....

  17. 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.

  18. 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.

  19. Radiofrequency ablation using a new type of internally cooled electrode with an adjustable active tip: An experimental study in ex vivo bovine and in vivo porcine livers

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Jihoon [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-dong, Gangnam-gu, Seoul 135-710 (Korea, Republic of); Kim, Young-sun, E-mail: youngskim@skku.edu [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-dong, Gangnam-gu, Seoul 135-710 (Korea, Republic of); Rhim, Hyunchul; Lim, Hyo K.; Choi, Dongil; Lee, Min Woo [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-dong, Gangnam-gu, Seoul 135-710 (Korea, Republic of)

    2011-03-15

    Purpose: The aims of this study were to evaluate the performance of radiofrequency (RF) ablation using a new type of internally cooled RF electrode with an adjustable active tip in an ex vivo bovine liver model and to determine if adjustment of the active tip length makes a significant difference in the size of ablation zone in an in vivo porcine liver model. Materials and methods: We performed ex vivo experiments by producing 100 RF ablation zones in 40 extracted bovine livers using a new type of RF electrode that had an adjustable active tip (adjustable electrode) (n = 50) and a conventional internally cooled electrode (conventional electrode) (n = 50). We also performed an in vivo study with the induction of 30 RF ablation zones in ten living porcine livers using the adjustable electrode with 2 cm (n = 15) and 3 cm (n = 15) active tip adjustments. The size (three perpendicular diameters), volume and ratio of the two axes of the ablation zone were macroscopically evaluated and were compared. Results: For the ex vivo study using a 2 cm and 3 cm active tip, there was no significant difference in ablation performance between the use of conventional and adjustable electrodes. For the use of the conventional and adjustable electrodes with 2 cm active tip, respectively, the volume was 10.75 {+-} 3.43 cm{sup 3} versus 10.64 {+-} 3.25 cm{sup 3} and the ratio of the two axes was 1.24 {+-} 0.16 versus 1.30 {+-} 0.17; p > 0.05. For the use of the conventional and adjustable electrodes with 3 cm active tip, respectively, the volume was 21.17 {+-} 4.09 cm{sup 3} versus 21.48 {+-} 3.51 cm{sup 3} and the ratio of the two axes was 1.28 {+-} 0.12 versus 1.28 {+-} 0.07; p > 0.05. For the in vivo study using the adjustable electrode, the ablation volume with the 2 cm adjustment was significantly smaller as compared to the 3 cm adjustment (5.29 {+-} 2.22 cm{sup 3} versus 13.44 {+-} 4.25 cm{sup 3}; p < 0.05) with no statistical difference for the ratio of the two axes (1.44 {+-} 0

  20. 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.

  1. 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.

  2. 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.

  3. Intratracheally administered titanium dioxide or carbon black nanoparticles do not aggravate elastase-induced pulmonary emphysema in rats.

    OpenAIRE

    Roulet Agnès; Armand Lucie; Dagouassat Maylis; Rogerieux Françoise; Simon-Deckers Angélique; Belade Esther; Van Nhieu Jeanne; Lanone Sophie; Pairon Jean-Claude; Lacroix Ghislaine; Boczkowski Jorge

    2012-01-01

    Abstract Background Titanium dioxide (TiO2) and carbon black (CB) nanoparticles (NPs) have biological effects that could aggravate pulmonary emphysema. The aim of this study was to evaluate whether pulmonary administration of TiO2 or CB NPs in rats could induce and/or aggravate elastase-induced emphysema, and to investigate the underlying molecular mechanisms. Methods On day 1, Sprague-Dawley rats were intratracheally instilled with 25 U kg−1 pancreatic porcine elastase or saline. On day 7, t...

  4. Liver Biopsy in Liver Transplant Recipients

    OpenAIRE

    Van Ha, Thuong G.

    2004-01-01

    Liver biopsy has been used in the assessment of the nature and course of liver diseases and to monitor treatments. In nontransplanted patients, liver biopsies have been well described. Less has been written on the biopsies of transplanted livers. In the liver transplant population, liver biopsy remains the “gold standard” for the diagnosis of rejection. The transplanted liver has additional considerations that can make biopsy less routine and more challenging.

  5. 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.

  6. 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

  7. Hepatoprotective effects of a self-micro emulsifying drug delivery system containing Silybum marianum native seed oil against experimentally induced liver injury.

    Science.gov (United States)

    Fehér, P; Ujhelyi, Z; Vecsernyés, M; Fenyvesi, F; Damache, G; Ardelean, A; Costache, M; Dinischiotu, A; Hermenean, A; Bácskay, I

    2015-04-01

    The main purpose of this study was to certify the effect of native silymarin oil (SM-oil) formulated in a self-microemulsifying drug delivery system (SMEDDS). The optimal formulation was 25% of SM-oil, 33.3 % of Cremophor RH40, 20% of Transcutol HP, 16.6% of Labrasol and 5% of Capryol 90. In this novel formulation the SM-oil was the active substance and the lipid part. The in vivo study examined the preventive effects of SMEDDS containing SM native seeds oil against carbon tetrachloride (CC14) induced hepatotoxicity in mice. Determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels and also liver histology investigations have been done. The liver antioxidant status was determined with the concentrations of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), and glutathione (GSH) hepatic lipid peroxidation was examined and expressed in terms of malondialdehyde (MDA) content. The plasma levels of AST and ALT significantly diminished by pre-treatment with 500 mg/kg and 1000 mg/kg SMEDDS. The pre-treatment with 500 mg/kg and 1000 mg/kg SMEDDS increased GSH level by about 6% respectively 24% compared to the CC14 group. Due to preventive administration of 500 mg/kg and 1000 mg/kg of SMEDDS in the intoxicated animals, MDA levels were reduced by 22% respectively 58%. Also, an insignificant rise by almost 17% and 19% in the animals treated with the both doses of SMEDDS could be noticed. It can be concluded that hepatotoxicity may be avoided by the oral application of our formulation. PMID:26012252

  8. 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.

  9. 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.

  10. 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.

  11. 77 FR 24415 - Inflation Adjustment of the Aggravated Maximum Civil Monetary Penalty for a Violation of a...

    Science.gov (United States)

    2012-04-24

    ... ``older safety statutes'': the Safety Appliance Acts (then codified at 45 U.S.C. 1-16); the Locomotive... $650, the ordinary maximum of $25,000, and the aggravated maximum CMP of $100,000). See 73 FR 79698...-adjusted $550. 69 FR 30591 (May 28, 2004) and 69 FR 62817 (Oct. 28, 2004). (In 2004, FRA had determined,...

  12. Does objectively measured daily duration of forward bending predict development and aggravation of low-back pain?

    DEFF Research Database (Denmark)

    Lagersted-Olsen, Julie; Thomsen, Birthe Lykke; Holtermann, Andreas;

    2016-01-01

    OBJECTIVES: The aim of this paper was to investigate if objectively measured daily duration of forward bending of the trunk increases the risk of the development or aggravation of low-back pain (LBP) over one year in a working blue-collar population by examining (i) the incidence rate of LBP among...

  13. 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

  14. Liver size determination in pediatrics using sonographic and scintigraphic techniques

    International Nuclear Information System (INIS)

    Knowledge of the normal liver size is essential for making the scintigraphic estimate of hepatomegaly. A nomogram for sonographic liver size versus height of the patient was developed for the normal pediatric patient. Liver size was measured as the longitudinal liver length in the plane midway between the xiphoid and the right lateral liver margin. Scintigraphic and sonographic measurements showed a good correlation. The scintigraphic nomogram was developed using the experimentally determined relationship between the two modalities. (auth)

  15. Liver transplantation

    OpenAIRE

    Rodríguez-Perálvarez, M; De La Mata, M; Burroughs, A K

    2014-01-01

    Purpose of review: Long-term survival of liver transplant recipients is threatened by increased rates of de-novo malignancy and recurrence of hepatocellular carcinoma (HCC), both events tightly related to immunosuppression. Recent findings: There is accumulating evidence linking increased exposure to immunosuppressants and carcinogenesis, particularly concerning calcineurin inhibitors (CNIs), azathioprine and antilymphocyte agents. A recent study including 219 HCC transplanted patients sh...

  16. Liver disease - resources

    Science.gov (United States)

    Resources - liver disease ... The following organizations are good resources for information on liver disease : American Liver Foundation -- www.liverfoundation.org Children's Liver Association for Support Services -- www.classkids.org Hepatitis ...

  17. 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 older. ...

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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.).

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Zhang, Ji; Qiao, Congzhen; Chang, Lin; Guo, Yanhong; Fan, Yanbo; Villacorta, Luis; Chen, Y Eugene; Zhang, Jifeng

    2016-01-01

    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. PMID:27294862

  5. 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. PMID:26661172

  6. 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.

  7. 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.

  8. Strenuous exercise aggravates MDMA-induced skeletal muscle damage in mice

    International Nuclear Information System (INIS)

    The aim of this study was to investigate the influence of ecstasy (MDMA) administration on body temperature and soleus muscle histology in exercised and non-exercised mice. Charles-River mice were distributed into four groups: Control (C), exercise (EX), MDMA treated (M), and M + EX. The treated animals received an i.p. injection (10 mg/kg) of MDMA (saline for C and EX), and the exercise consisted of a 90 min level run at a velocity of 900 m/h, immediately after the MDMA or saline administration. Body temperature was recorded every 30 min via subcutaneous implanted transponder. Animals were sacrificed 1.5, 25.5, and 49.5 h after i.p. injection and the soleus muscles were removed and processed for light and electron microscopy. The MDMA-treated animals showed a significant increase in body temperature (similar in M and M + EX groups), reaching the peak 90 min after i.p. administration; their temperature remained higher than control for more than 5 h. The EX group evidenced a similar and parallel, yet lower temperature increase during exercise and recovery. Morphological signs of damage were rarely encountered in the EX group; they were more pronounced in M group and even aggravated in M + EX group. In conclusion, MDMA and exercise per se increased body temperature but in conjunction did not have a cumulated effect. However, ecstasy and concomitant physical activity might severely accumulate with regard to skeletal muscle toxicity and may lead to rhabdomyolysis

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

    Directory of Open Access Journals (Sweden)

    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.

  10. GSN antibody pretreatment aggravates radiation-induced lung injury in mice

    International Nuclear Information System (INIS)

    Radiation-induced lung injury is one of the main dose limiting factors for thoracic radiation therapy. Gelsolin (GSN) is a widespread, multifunctional regulator of cellular structure and metabolism. In this work, the roles of GSN in radiation-induced lung injury in Balb/c mice were studied. The GSN levels in plasma reduced progressively in 72 hours after irradiation, and then increased gradually. GSN contents in the bronchoalveolar lavage (BAL) fluid increased after thoracic irradiation, whereas mRNA levels of GSN in the lung tissue decreased significantly within 24 hours after irradiation and then increased again. Mice were intravenously injected with 50 μg GSN antibody 0.5 hour before 20 Gy of thoracic irradiation. GSN antibody pretreatment increased lung inflammation, protein concentration in the BAL fluid and leukocytes infiltration in the irradiated mice. The activities of superoxidase dismutase (SOD) in the plasma and the BAL fluid in irradiated mice injected with GSN antibody were less than that of control groups, whereas the levels of malondialdehyde (MDA) increased. These results suggest that pretreatment of GSN antibody may aggravate radiation-induced pneumonitis. (authors)

  11. 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

    Directory of Open Access Journals (Sweden)

    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

  12. 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.

  13. The ultrastructural changes in the liver cells induced by high doses of Benzodiazepine Tranquilizing drugs: An experimental transmission electron microscopic study on male guinea pigs

    International Nuclear Information System (INIS)

    Benzodiazepines are tranquilizing psychotropic drugs. Unfortunately, despite their therapeutic benefits, they are illegally consumed in high doses by some addicts to reach a sedative, exhilarative and euphoria state similar to that produced by narcotic substances. The present study, using transmission electron microscope on male guinea pigs, aims to investigate the potential ultrastructural changes in the liver cells induced by the high doses of Benzodiazepines. Animals in three treated groups administrated a daily combined dose consisted of (10mg Alprazolam with 10mg Diazepam/day/animal) for three different treatment periods: 7, 15, and 25 days. The ultrastructural examination of the hepatocytes of the animals treated for 15 days showed limited changes in the form of marginal heterochromatine accompanied with marginal nucleoli enlargement. On the other hand, severe ultrastructural damages are observed in the animals treated for 25 days, which appeared in the following various patterns: fatty degeneration of the hepatocytes as indicated by the accumulation of large number of lipid droplets in the cytoplasm, marked nuclear atrophy in some necrotic hepatocytes, massive nuclear degeneration in other hepatocytes, mitochondrial damages in the form of cristea destruction accompanied with abnormal oval shape, massive lysis of the cytoplasmic organelles with severe plasma membrane rupture. In conclusion, the observed ultrastructural damages in the present study may refer to the potential hepatotoxic effects of the high dose of Benzodiazepins. It is recommended that much more official restrictions should be applied on the pharmacies sector to prevent any illegal selling of these drugs in order to prevent abusers from obtaining them, as unfortunately in some developing countries the illegal selling of these drugs is known to occur due to the absence of official control. (author)

  14. Liver function

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930536 Applied anatomy for interhepatic porto-caval shunt.DU Xiangke(杠湘珂),et al.DeptRadiol,Beijing People’s Hosp,Beijing Med U-niv,Beijing,100044.Chin J Radiol 1993;27(3):148—151.The results of measurement of the anatormicalrelationship of hepatic and portal vein in 70 hu-man liver specimens were reported including theirdistance and overlapping areas.The resultsdemonstrated that,when the catheter enteredthe posterior segment of IVC in the liver andthen passed into the left,middle or right branch-es of hepatic vein for an average of 4—5cm,thesegmental branches of portal vein would be over-lapped.The authors suggested that the catheter

  15. 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.

  16. Engineering liver

    OpenAIRE

    Griffith, Linda G.; Wells, Alan; Stolz, Donna Beer

    2013-01-01

    Interest in “engineering liver” arises from multiple communities: therapeutic replacement; mechanistic models of human processes; and drug safety and efficacy studies. An explosion of micro- and nano-fabrication, biomaterials, microfluidic, and other technologies potentially afford unprecedented opportunity to create microphysiological models of human liver, but engineering design principles for how to deploy these tools effectively towards specific applications, including how to define the e...

  17. 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

  18. 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.

  19. 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.

  20. 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.

  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. 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.

  3. 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, Pacute lymphoblastic leukemia does not seem to influence the occurrence of symptomatic osteonecrosis. 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.

  4. 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.

  5. MDA-5 activation by cytoplasmic double-stranded RNA impairs endothelial function and aggravates atherosclerosis.

    Science.gov (United States)

    Asdonk, Tobias; Steinmetz, Martin; Krogmann, Alexander; Ströcker, Christine; Lahrmann, Catharina; Motz, Inga; Paul-Krahe, Kathrin; Flender, Anna; Schmitz, Theresa; Barchet, Winfried; Hartmann, Gunther; Nickenig, Georg; Zimmer, Sebastian

    2016-09-01

    Recent studies have highlighted the relevance of viral nucleic acid immunorecognition by pattern recognition receptors in atherogenesis. Melanoma differentiation associated gene 5 (MDA-5) belongs to the intracellular retinoic acid inducible gene-I like receptors and its activation promotes pro-inflammatory mechanisms. Here, we studied the effect of MDA-5 stimulation in vascular biology. To gain insights into MDA-5 dependent effects on endothelial function, cultured human coronary artery endothelial cells (HCAEC) were transfected with the synthetic MDA-5 agonist polyIC (long double-stranded RNA). Human coronary endothelial cell expressed MDA-5 and reacted with receptor up-regulation upon stimulation. Reactive oxygen species formation, apoptosis and the release of pro-inflammatory cytokines was enhanced, whereas migration was significantly reduced in response to MDA-5 stimulation. To test these effects in vivo, wild-type mice were transfected with 32.5 μg polyIC/JetPEI or polyA/JetPEI as control every other day for 7 days. In polyIC-treated wild-type mice, endothelium-dependent vasodilation and re-endothelialization was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticles and circulating endothelial progenitor cells significantly elevated compared to controls. Importantly, these effects could be abrogated by MDA-5 deficiency in vivo. Finally, chronic MDA-5 stimulation in Apolipoprotein E/toll-like receptor 3 (TLR3) double(-) deficient (ApoE(-/-) /TLR3(-/-) ) mice-enhanced atherosclerotic plaque formation. This study demonstrates that MDA-5 stimulation leads to endothelial dysfunction, and has the potential to aggravate atherosclerotic plaque burden in murine atherosclerosis. Thus, the spectrum of relevant innate immune receptors in vascular diseases and atherogenesis might not be restricted to TLRs but also encompasses the group of RLRs including MDA-5. PMID:27130701

  6. Amorphous silica nanoparticles size-dependently aggravate atopic dermatitis-like skin lesions following an intradermal injection

    Directory of Open Access Journals (Sweden)

    Hirai Toshiro

    2012-02-01

    Full Text Available Abstract Background Due to the rising use of nanomaterials (NMs, there is concern that NMs induce undesirable biological effects because of their unique physicochemical properties. Recently, we reported that amorphous silica nanoparticles (nSPs, which are one of the most widely used NMs, can penetrate the skin barrier and induce various biological effects, including an immune-modulating effect. Thus, it should be clarified whether nSPs can be a risk factor for the aggravation of skin immune diseases. Thus, in this study, we investigated the relationship between the size of SPs and adjuvant activity using a model for atopic dermatitis. Results We investigated the effects of nSPs on the AD induced by intradermaly injected-mite antigen Dermatophagoides pteronyssinus (Dp in NC/Nga mice. Ear thickness measurements and histopathological analysis revealed that a combined injection of amorphous silica particles (SPs and Dp induced aggravation of AD in an SP size-dependent manner compared to that of Dp alone. In particular, aggravation was observed remarkably in nSP-injected groups. Furthermore, these effects were correlated with the excessive induction of total IgE and a stronger systemic Th2 response. We demonstrated that these results are associated with the induction of IL-18 and thymic stromal lymphopoietin (TSLP in the skin lesions. Conclusions A particle size reduction in silica particles enhanced IL-18 and TSLP production, which leads to systemic Th2 response and aggravation of AD-like skin lesions as induced by Dp antigen treatment. We believe that appropriate regulation of nanoparticle physicochemical properties, including sizes, is a critical determinant for the design of safer forms of NMs.

  7. 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...

  8. 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-

  9. 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

  10. 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。

  11. 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.

  12. Nur77 exacerbates PC12 cellular injury in vitro by aggravating mitochondrial impairment and endoplasmic reticulum stress

    Science.gov (United States)

    Gao, Huimin; Chen, Zhaoyu; Fu, Yongmei; Yang, Xiaoyan; Weng, Ruihui; Wang, Rui; Lu, Jianjun; Pan, Mengqiu; Jin, Kunlin; McElroy, Chris; Tang, Beisha; Xia, Ying; Wang, Qing

    2016-01-01

    The nuclear orphan receptor, Nur77 plays important roles in neuroimflammation, apoptosis, and dopaminergic neurodegeneration. We conducted a further mechanistic investigation into the association of Nur77 with cell death. Cytosporone B (Csn-B), an agonist for Nur77, and Nur77 knockdown were adopted in the 6-hydroxydopamine (OHDA)-lesioned PC12 cells to investigate the mechanisms underlying Nur77-mediated injury. The 6-OHDA incubation caused Nur77 translocation from the nucleus to cytosol and Endoplasm reticulum (ER) and induced co-localization of Tom20/Nur77 and Protein Disulfide Isomerase (PDI)/Nur77. Nur77 activation further decreased cell viability, aggravated intracellular LDH release, intracellular Ca2+, ROS levels, apoptosis, ER tress and, mitochondrial transmembrane potential (ΔΨm) decline. In addition, Nur77 activation significantly enhanced the efficiency of autophagy as indicated by an up-regulation of Beclin-1/LC-3 and downregulation of p62, and aggravated mitochondrial dysfunctions and ER stress as shown by increased HSP60/Cytochrome C (Cyt C) and CHOP-ATF3 levels respectively. These changes could be partially reversed by Nur77 knockdown. Moreover, Nur77 activation upregulated PINK1 and downregulated Parkin levels. We conclude that Nur77 exacerbates PC12 cell death at least partially by aggravating the mitochondrial impairment and ER stress and enhancing autophagy. We propose that Nur77 is likely a critical target in the PD therapy. PMID:27679973

  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 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.

  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. 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).

  17. 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

  18. MEDICINAL PLANTS AGAINST LIVER DISEASES

    Directory of Open Access Journals (Sweden)

    Pandey Govind

    2011-05-01

    Full Text Available India is the largest producer of medicinal plants and is rightly called the “Botanical Garden of the World”. The medicinal plants have very important place in the health and vitality of human beings as well as animals. As per the WHO estimates, about three quarters of the world’s population currently use herbs and other traditional medicines to cure various diseases, including liver disorders. Hence, several phytomedicines (medicinal plants or herbal drugs are now used for the prevention and treatment of various liver disorders. Although experimental studies have been conducted on a number of these plants and their formulations, however, only some plants have clearly shown the hepatogenic / hepatoprotective effects against liver diseases or hepatotoxicity caused by variety of hepatotoxic agents such as chemicals, drugs, pollutants, and infections from parasites, bacteria or viruses (e.g., hepatitis A, B and C, etc. Indeed, to obtain satisfactory herbal drugs for treating severe liver diseases, the medicinal plants must be evaluated systematically for properties like antiviral activity (Hepatitis B, Hepatitis C, etc., antihepatotoxicity activity (antioxidants and others, stimulation of liver regeneration and choleretic activity. A combination of different herbal extracts / fractions is likely to provide desired activities to cure severe liver diseases. The medicinal plants contain several phytochemicals which possess strong antioxidant property, leading to antihepatotoxic activity.

  19. 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.

  20. 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

  1. Pyogenic liver abscess

    Science.gov (United States)

    Liver abscess; Bacterial liver abscess ... There are many potential 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 ...

  2. Vascular endothelial growth factor-receptor 1 inhibition aggravates diabetic nephropathy through eNOS signaling pathway in db/db mice.

    Directory of Open Access Journals (Sweden)

    Keun Suk Yang

    Full Text Available The manipulation of vascular endothelial growth factor (VEGF-receptors (VEGFRs in diabetic nephropathy is as controversial as issue as ever. It is known to be VEGF-A and VEGFR2 that regulate most of the cellular actions of VEGF in experimental diabetic nephropathy. On the other hand, such factors as VEGF-A, -B and placenta growth factor bind to VEGFR1 with high affinity. Such notion instigated us to investigate on whether selective VEGFR1 inhibition with GNQWFI hexamer aggravates the progression of diabetic nephropathy in db/db mice. While diabetes suppressed VEGFR1, it did increase VEGFR2 expressions in the glomerulus. Db/db mice with VEGFR1 inhibition showed more prominent features with respect to, albuminuria, mesangial matrix expansion, inflammatory cell infiltration and greater numbers of apoptotic cells in the glomerulus, and oxidative stress than that of control db/db mice. All these changes were related to the suppression of diabetes-induced increases in PI3K activity and Akt phosphorylation as well as the aggravation of endothelial dysfunction associated with the inactivation of FoxO3a and eNOS-NOx. In cultured human glomerular endothelial cells (HGECs, high-glucose media with VEGFR1 inhibition induced more apoptotic cells and oxidative stress than did high-glucose media alone, which were associated with the suppression of PI3K-Akt phosphorylation, independently of the activation of AMP-activated protein kinase, and inactivation of FoxO3a and eNOS-NOx pathway. In addition, transfection with VEGFR1 siRNA in HGECs also suppressed PI3K-Akt-eNOS signaling. In conclusion, the specific blockade of VEGFR1 with GNQWFI caused severe renal injury related to profound suppression of the PI3K-Akt, FoxO3a and eNOS-NOx pathway, giving rise to the oxidative stress-induced apoptosis of glomerular cells in type 2 diabetic nephropathy.

  3. Liver function

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930136 Epidermal growth factor for enhanc-ing DNA synthesis of hepatocytes and its pro-tecting effect on animals with liver injury.HUANG Huili(黄慧俐),et al.Dept Infect Dis,Southwest Hosp,3rd Milit Med Univ,Chongqing,630038.Natl Med J China 1992;72(10):604-607.Epidermal growth factor(EGF)was purifiedchromatographically from mice submaxillaryglands,and its activity and electrophoretic pure-ness were identified.The effect of EGF,glucagon-insulin(G-Ins)and EGF-glueagon-insulin mixture(EGF-G-Ins)onstimulation of DNA synthesis in primary cul-tures of rat hepatocytes and their protective ef-

  4. Amebic liver abscess

    Science.gov (United States)

    ... liver in response to an intestinal parasite called Entamoeba histolytica . ... Amebic liver abscess is caused by Entamoeba histolytica. This ... dysentery. After an infection has occurred, the parasite may ...

  5. 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 ...

  6. 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.

  7. S-nitroso-N-acetylcysteine ameliorates ischemia-reperfusion injury in the steatotic liver

    Directory of Open Access Journals (Sweden)

    Wellington Andraus

    2010-01-01

    Full Text Available BACKGROUND: Steatosis is currently the most common chronic liver disease and it can aggravate ischemia-reperfusion (IR lesions. We hypothesized that S-nitroso-N-acetylcysteine (SNAC, an NO donor component, can ameliorate cell damage from IR injury. In this paper, we report the effect of SNAC on liver IR in rats with normal livers compared to those with steatotic livers. METHODS: Thirty-four rats were divided into five groups: I (n=8, IR in normal liver; II (n=8, IR in normal liver with SNAC; III (n=9, IR in steatotic liver; IV (n=9, IR in steatotic liver with SNAC; and V (n=10, SHAN. Liver steatosis was achieved by administration of a protein-free diet. A SNAC solution was infused intraperitoneally for one hour, beginning 30 min. after partial (70% liver ischemia. The volume of solution infused was 1 ml/100 g body weight. The animals were sacrificed four hours after reperfusion, and the liver and lung were removed for analysis. We assessed hepatic histology, mitochondrial respiration, oxidative stress (MDA, and pulmonary myeloperoxidase. RESULTS: All groups showed significant alterations compared with the group that received SHAN. The results from the steatotic SNAC group revealed a significant improvement in liver mitochondrial respiration and oxidative stress compared to the steatotic group without SNAC. No difference in myeloperoxidase was observed. Histological analysis revealed no difference between the non-steatotic groups. However, the SNAC groups showed less intraparenchymal hemorrhage than groups without SNAC (p=0.02. CONCLUSION: This study suggests that SNAC effectively protects against IR injury in the steatotic liver but not in the normal liver.

  8. Artificial liver support: a real step forward.

    Science.gov (United States)

    Saliba, F; Samuel, D

    2015-02-01

    Since the early 1960s, several authors reported on the use of some experimental artificial liver devices in order to support patients with either acute liver failure (ALF) or end-stage chronic liver disease. In the 1980s, liver transplantation became an established real treatment replacing the whole liver with a major survival benefit. In the 1990s, the concept of albumin dialysis appeared as a new revolution in the concept of dialysis with the great capacity of removal of toxins, drugs and molecules strongly bound to albumin. Currently, three artificial liver support devices are available: The MARS®, the Prometheus® and the SPAD®. The most widely studied and used system is the MARS® that uses albumin dialysis to replace the detoxification function of the liver. MARS has shown in several uncontrolled studies and few randomized studies an improvement in the patient condition in terms of clinical symptoms (hepatic encephalopathy, pruritus, jaundice) and in liver and kidney biological parameters bringing these patients safely to liver transplantation. MARS® has shown for some patients with ALF (mainly paracetamol intoxication) an improvement of spontaneous or transplant free survival. The use of MARS in acute on chronic liver failure (ACLF) require further studies based on strict definition of the syndrome. The use of albumin dialysis technique, require the performance of multiple sessions of treatment or even (in situations of ALF) a continuous treatment in order to improve spontaneous recovery or bridge these patients to liver transplantation. The performance of these systems would need further improvement. Large randomized trials are still needed in both patients with ALF and ACLF to establish the indications, the timing and the real place of liver support therapies. Meanwhile, early use of these devices in patients with ALF and ACLF could be considered as an additional tool among others in the management of these patients in specialized liver units. PMID

  9. 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-

  10. Alcohol-Related Liver Disease

    Science.gov (United States)

    ... to run events. Please support us. Donate | Volunteer Alcohol-Related Liver Disease Discussion on Inspire Support Community ... Liver > Liver Disease Information > Alcohol-Related Liver Disease Alcohol-Related Liver Disease Explore this section to learn ...

  11. Liver Disease and Pulmonary Hypertension

    Science.gov (United States)

    Liver Disease Pulmonary & PH Hypertension Did you know that if you have liver disease, you are at risk for pulmonary ... to the liver without cirrhosis. How does liver disease relate to pulmonary hypertension? Liver disease can cause what is known ...

  12. Alcoholic Liver Disease and Liver Transplantation.

    Science.gov (United States)

    Gallegos-Orozco, Juan F; Charlton, Michael R

    2016-08-01

    Excessive alcohol use is a common health care problem worldwide and is associated with significant morbidity and mortality. Alcoholic liver disease represents the second most frequent indication for liver transplantation in North America and Europe. The pretransplant evaluation of patients with alcoholic liver disease should aim at identifying those at high risk for posttransplant relapse of alcohol use disorder, as return to excessive drinking can be deleterious to graft and patient survival. Carefully selected patients with alcoholic liver disease, including those with severe alcoholic hepatitis, will have similar short-term and long-term outcomes when compared with other indications for liver transplantation. PMID:27373614

  13. Experimental study on ablating goat liver tissue with ultrasound imaging guided percutaneous irreversible electroporation%超声引导不可逆电穿孔消融山羊肝脏的实验研究

    Institute of Scientific and Technical Information of China (English)

    刘颖; 周玮; 熊正爱; 李成祥; 姚陈果

    2011-01-01

    Objective To investigate the proper method of percutaneous irreversible eletroporation (IRE) to ablate goat liver tissue under ultrasonic guidance, and observe the features of ultrasound imaging and histological changes. Methods The pulse electric fields (PEFs) with permanent duration (lOO μs) , frequency (1Hz) , voltage (2000V) and pulses (120 pieces) were applied to the electrodes, and the electrodes were placed into goats' liver under ultrasound guidance through the animal skin to the target area. The treated area was observed by real-time ultrasound scanning, and the histopathological changes were assessed by hematoxylin and eosin (HE) staining under light microscope at the time of 0h and 24h after IRE ablation. The circumscribed ablated area was compared with that of finite element modeling (FEM) calculation method. Results Ultrasound imaging guidance was accurate in focusing on the target area. Imaging captured by the ultrasound after IRE procedure was quite different from that of the normal liver imaging. Complete hepatic cell death with a sharp demarcation between the ablated zone and the non-ablated zone was well visualized 24 hours after the procedure. Necrospy-based measurement demonstrated a high consistence with FEM-anticipated ablation zones. Conclusion With real-time monitoring by ultrasonography and well-controlled ablation of the target tissue, percutaneous IRE can provide a novel and unique ablative method for cancer treatment. The present paper proides a fundamental experimental work for future studies on clinical application of IRE.%目的 探讨超声引导经皮穿刺不可逆性电穿孔(IRE)微创消融山羊肝脏组织的可行性、B超影像学特点及其病理学变化.方法 4~6月龄山羊4只,体重25~30kg,采用同定脉宽100μs、频率1Hz、电压2000V的脉冲电场,120个脉冲,经彩色超声探头引导电极针经皮定位穿刺处理肝脏组织,观察处理过程中及处理后即刻、24h靶区B超灰度变化和

  14. Cod Liver Oil

    Science.gov (United States)

    Cod liver oil can be obtained from eating fresh cod liver or by taking supplements. Cod liver oil is used for high cholesterol, high triglycerides, ... ear infections (otitis media). Some people put cod liver oil on their skin to speed wound healing. ...

  15. Tolerance Induction in Liver

    OpenAIRE

    M.H Karimi; Geramizadeh, B; Malek-Hosseini, S. A.

    2015-01-01

    Liver is an exclusive anatomical and immunological organ that displays a considerable tolerance effect. Liver allograft acceptance is shown to occur spontaneously within different species. Although in human transplant patients tolerance is rarely seen, the severity level and cellular mechanisms of transplant rejection vary. Non-paranchymal liver cells, including Kupffer cells, liver sinusoidal endothelial cells, hepatic stellate cells, and resident dendritic cells may participate in liver tol...

  16. 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)

  17. Liver resection in liver transplant recipients

    Institute of Scientific and Technical Information of China (English)

    Gabriele Marangoni; Walid Faraj; Harsheet Sethi; Mohamed Rela; Paolo Muiesan; Nigel Heaton

    2008-01-01

    BACKGROUND: Liver resection after liver transplantation is a relatively uncommon procedure. Indications for liver resection include hepatic artery thrombosis (HAT), non-anastomotic biliary stricture (ischemic biliary lesions), liver abscess, liver trauma and recurrence of hepatocellular carcinoma (HCC). Organ shortage and lower survival after re-transplantation have encouraged us to make attempts at graft salvage. METHODS: Eleven resections at a mean of 59 months after liver transplantation were made over 18 years. Indications for liver resection included HCC recurrence in 4 patients, ischemic cholangiopathy, segmental HAT, sepsis and infected hematoma in 2 each, and ischemic segmentⅣafter split liver transplantation in 1. RESULTS: There was no perioperative mortality. Morbidity included one re-laparotomy for small bowel perforation, one bile leak treated conservatively, one right subphrenic collection, one wound infection and 5 episodes of Gram-negative sepsis. One patient underwent re-transplantation 4 months after resection for chronic rejection. There were 3 deaths, two from HCC recurrence and one from post-transplant lymphoproliferative disorder. The overall mean follow-up after resection was 48 months. CONCLUSIONS: Liver resection in liver transplant recipients is safe, and has good outcome in selected patients and avoids re-transplantation in the majority of patients. Recipients with recurrent HCC in graft may beneift from resection, but cure is uncommon.

  18. 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

  19. Aggravation of serum Hepatocyte Growth Factor levels during hepato carcinogenesis in Rats

    International Nuclear Information System (INIS)

    Hepatocyte growth factor (HGF) has an essential role during liver development and it plays an important role in the regeneration and repair of injured tissues and acting as a mitogen, motogen and morphogens for a variety of epithelial cells. The role of HGF in carcinogenesis is in straggle and so, the present study aimed to through light through the level of HGF during different steps of carcinogenesis. Forty male rats were given diethylnitrosamine (DEN) in drinking water (100 mg/l) for up to 16 weeks. Eight rats were sacrificed at 8, 12 and 16 weeks. Besides, 8 hepatoma bearing rats were exposed to a single dose gamma irradiation (3 Gy) were sacrificed after 2 weeks from exposure (2 rats died, 36 hrs post irradiation) and 8 hepatoma bearing rats were sacrificed after 4 weeks from receiving a combined antioxidant (N-acetylcysteine and Lmethionine). Serum HGF was assayed by enzyme linked immunosorbent assay (ELISA). Serum HGF level in DEN treated rats and in exposed hepatoma bearing rats was significantly higher than in control rats whereas, serum HGF level after treatment with N acetylcysteine and L-methionine for 4 weeks was significantly decreased than DEN treated rats and concluded that serum HGF may play a role during promotion and progression of hepatocellular carcinoma (HCC) and during treatment

  20. 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.

  1. Metabolic therapy: lessons from liver diseases.

    Science.gov (United States)

    Garcia-Ruiz, Carmen; Marí, Montserrat; Colell, Anna; Morales, Albert; Fernandez-Checa, Jose C

    2011-12-01

    Fatty liver disease is one of most prevalent metabolic liver diseases, which includes alcoholic (ASH) and nonalcoholic steatohepatitis (NASH). Its initial stage is characterized by fat accumulation in the liver, that can progress to steatohepatitis, a stage of the disease in which steatosis is accompanied by inflammation, hepatocellular death, oxidative stress and fibrosis. Recent evidence in experimental models as well as in patients with steatohepatitis have uncovered a role for cholesterol and sphingolipids, particularly ceramide, in the transition from steatosis to steatohepatitis, insulin resistance and hence disease progression. Cholesterol accumulation and its trafficking to mitochondria sensitizes fatty liver to subsequent hits including inflammatory cytokines, such as TNF/Fas, in a pathway involving ceramide generation by acidic sphingomyelinase (ASMase). Thus, targeting both cholesterol and/or ASMase may represent a novel therapeutic approach of relevance in ASH and NASH, two of the most common forms of liver diseases worldwide. PMID:21933146

  2. Transcriptional Regulation of the Group IIA Secretory Phospholipase A2 Gene by C/EBPδ in Rat liver and its Relationship to Hepatic Gluconeogenesis during Sepsis

    Science.gov (United States)

    Yang, Rei-Cheng; Hsu, Chin; Lee, Tzu-Ying; Kuo, Kung-Kai; Wu, Shou-Mei; Chen, Yen-Hsu; Ho, Mei-Ling; Yao, Xing-Hai; Liu, Chia-Hsiung; Liu, Maw-Shung

    2014-01-01

    Background The present study was undertaken to test hypothesis that altered transcription of secretory Phospholipase A2 (sPLA2) gene in rat liver is regulated by CCAAT/enhancer binding protein δ (C/EBPδ), and to assess its relationship to hepatic gluconeogenesis during the progression of sepsis. Methods Sepsis was induced by Cecal Ligation and Puncture (CLP). Experiments were divided into three groups, control, early sepsis (9 h after CLP), and late sepsis (18 h after CLP). Results DNA mobility and super shift assays reveal that C/EBP complexes in the liver consisted of at least three isoforms: C/EBPα, C/EBPβ, and C/EBPδ; and various C/EBP isoforms were capable of interacting with each other. Hepatocyte transfection experiments demonstrate that under normal conditions, binding of C/EBPδ to sPLA2 gene enhanced sPLA2 promoter activity and the binding resulted in an increase in hepatic gluconeogenesis. Under pathological conditions such as sepsis, binding of C/EBPδ to sPLA2 promoter increased during early and late phases of sepsis, and the increases in C/EBPδ binding correlated with increases in sPLA2 mRNA abundance and sPLA2 protein levels. Under otherwise the identical experimental conditions, hepatic gluconeogenesis was reduced during early and late phases of sepsis and the sepsis-induced reductions in liver gluconeogenesis were aggravated by binding of C/EBPδ to sPLA2 gene. Conclusions These results link C/EBPδ binding to altered sPLA2 promoter, and to hepatic gluconeogenesis under normal and pathological conditions. It is suggested that C/EBPδ-sPLA2- hepatic gluconeogenesis may function as a signalling axis affecting glucose homeostasis during the progression of sepsis. PMID:25035816

  3. 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.

  4. Gene therapy of liver cancer

    OpenAIRE

    Hernandez-Alcoceba, R. (Rubén); B. Sangro; Prieto, J.

    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/pro-drug 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 reac...

  5. Nutrition in Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    Marco Silva

    2015-11-01

    The large majority of patients with grade I/II hepatic encephalopathy can tolerate a regular diet. Protein restriction can aggravate malnutrition and is not recommended, except in cases of hepatic encephalopathy unresponsive to optimized therapy.

  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. 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.

  8. Biomarkers for liver fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    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.

  9. 正常及肝纤维化小鼠大范围肝切除后的肝再生研究%The research of liver regeneration betweennormal mice and liver fibrosis mice after a wide range of hepatectomy

    Institute of Scientific and Technical Information of China (English)

    张迪; 刘子荣; 陈峰; 崔子林; 张雅敏

    2016-01-01

    the experimental group by administration of40% carbon tetrachoride(CCl4) corn oil solution, while the control group were given corn oil only. Two groups were subjected to the left and middle hepatic lobe liver resection after6 weeks. The blood samples and remaining liver tissue were collected at3 hours,6 hours,12 hours,24 hours,48 hours and72 hours after hepatectomy to detect the serum alanine aminotransferase(ALT), aspartate transaminase(AST) levels, liver tissue pathology, the liver weight ratio and proliferating cell nuclear antigen(PCNA), the differences of damage and regeneration were observed.Results ALT and AST were significantly higher in the experimental group as compared to the controls after hepatectomy. They reached peak value at12 hours and had significant differences compared with control group〔ALT(U/L):923.11±41.26vs.869.55±33.65;AST(U/L):976.69±48.65vs.744.77±21.42, allP<0.05〕. Pathology results showed that experimental group were damaged more seriously than controls. Liver regeneration was slow in the experimental group as compared to the controls in the liver weight ratio and PCNA staining. In48 hours, it reached peak value and the number of PCNA positive cells were significantly decreased compared with control group(number of PCNA positive cells:92.33±10.68 vs.176.33±14.74, P<0.05).Conclusion Liver fibrosis lesions may aggravate liver injury and slow down the liver regeneration after a wide range of hepatectomy in mice.

  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. 人胚胎干细胞来源的肝细胞小鼠移植的实验研究%An experimental study on human embryonic stem cell-derived hepatocytes transplantation into liver decompensated mice

    Institute of Scientific and Technical Information of China (English)

    梁道明; 张毅; 罗敏; 段永庆; 周粼; 王华

    2015-01-01

    Objective To study the ability of human embryonic stem cells to integrate into mouse liver and to repair chronic liver injury of the recipient.Methods On day 1,day-7 and day-15 after human embryonic stem cells were induced to differentiate into hepatocyte-like cells and were transplanted into mice with chronic liver failure,liver histopathology,liver function,liver tissue regeneration and mature hepatocytes of mice were tested respectively.Results Hepatic tissue pathology of mice significantly improved after transplantation and necrotic foci diminished,hemorrhage and congestion of hepatic cells relieved,and liver function improved.It was observed that human embryonic stem cells survived,proliferated,integrated with host liver,and differentiated into mature hepatocytes.Conclusions Human embryonic stem cells xenotransplanted into mice can participated liver tissue regeneration to some extent,and differentiated into functional liver cells.%目的 将人胚胎干细胞诱导分化成的肝细胞移植入小鼠模型,探讨其细胞整合到肝脏的能力,并观察对肝脏细胞损害的修复作用.方法 将人胚胎于细胞诱导分化成的肝样细胞移植入慢性肝功能衰竭小鼠体内l、7、15 d后,检测小鼠的肝脏病理组织学、肝功能以及分化肝细胞参与受体肝组织的再生及分化为成熟的肝细胞的情况.结果 移植后肝脏组织病理变化明显改善,表现为肝细胞以变性和炎性细胞浸润为主,坏死灶小、充血以及出血现象减轻;同时肝功能好转.分离到的人胚胎干细胞可在肝受损小鼠体内存活,增殖,整合,并能分化为成熟的肝细胞.结论 将人胚胎干细胞移植入小鼠体内后参与受体肝组织的再生,并能分化成功能性的肝细胞.

  12. Sitosterolemia in ABC-transporter G5-deficient mice is aggravated on activation of the liver-X receptor (vol 126, pg 944, 2004)

    NARCIS (Netherlands)

    Plosch, T; Bloks, VW; Terasawa, Y; Berdy, S; Siegler, K; van der Sluijs, F; Kema, IP; Groen, AK; Shan, B; Kuipers, F; Schwartz, M

    2004-01-01

    Background & Aims: Mutations in either adenosine triphosphate-binding cassette (ABC) half-transporter G5 or G8 cause sitosterolemia. It has been proposed that ABCG5/ABCG8 heterodimers mediate secretion of plant sterols and cholesterol by hepatocytes into bile and their efflux from enterocytes into t

  13. Towards a new therapy protocol for liver metastases. Effect of boron compounds and BNCT on normal liver regeneration

    International Nuclear Information System (INIS)

    The Taormina project developed a new method for BNCT treatment of multifocal unresectable liver metastases based on whole liver autograft. The Roffo Institute liver surgeons propose a new technique based on partial liver autograft that would pose less risk to the patient but would require significant healthy liver regeneration following BNCT. The aim of the present study was to assess the effect of BPA, GB-10 (Na210B10H10) and (GB-10 + BPA) and of BNCT mediated by these boron compounds on normal liver regeneration in the Wistar rat. Normal liver regeneration, body weight, hemogram, liver and kidney function were assessed following partial hepatectomy post administration of BPA, GB-10 or (GB-10 + BPA) and post in vivo BNCT at the RA-6 Reactor. These end-points were evaluated 9 days following partial hepatectomy, the time at which complete liver regeneration occurs in untreated controls. The corresponding biodistribution studies were conducted to perform dosimetric calculations. BPA, GB-10 and (GB-10 + PBA) and in vivo BNCT mediated by these boron compounds in dose ranges compatible with therapy did not cause alterations in the outcome of normal liver regeneration, and did not induce alterations in body weight, hemogram, liver or kidney function. The experimental data available to date support the development of a new BNCT protocol for the treatment of liver metastases that requires the regeneration of normal liver past-BNCT. (author)

  14. CT-based liver volumetry in a porcine model: impact on clinical volumetry prior to living donated liver transplantation

    International Nuclear Information System (INIS)

    Purpose: Exact preoperative determination of the liver volume is of great importance prior to hepatobiliary surgery, especially in living donated liver transplantation (LDLT). In the current literature, a strong correlation between preoperatively calculated and intraoperatively measured liver volumes has been described. Such accuracy seems questionable, primarily due to a difference in the perfusion state of the liver in situ versus after explantation. Purpose of the study was to asses the influence of the perfusion state on liver volume and the validity of the preoperative liver volumetry prior to LDLT. Methods: In an experimental study, 20 porcine livers were examined. The livers were weighted and their volumes were determined by water displacement prior and after fluid infusion to achieve a pressure physiologically found in the liver veins. The liver volumes in the different perfusion states were calculated based on CT-data. The calculated values were compared with the volume measured by water displacement and the weight of the livers. Results: Assessment of calculated CT volumes and water displacements at identical perfusion states showed a tight correlation and differed on average by 4 ± 5%. However, livers before and after fluid infusion showed a 33 ± 8% (350 ± 150 ml) difference in volume. Conclusion: CT-volumetry acquires highly accurate data as confirmed by water displacement studies. However, the perfusion state has major impact on liver volume, which has to be accounted for in clinical use. (orig.)

  15. 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.

  16. 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.

  17. 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.

  18. 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 ...

  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. Diet and Your Liver

    Science.gov (United States)

    ... the scarring and hardening of the liver. Diet Recommendations: • Limit salt and foods that contain a lot of salt • Talk to your doctor about how much protein to have in your diet Fatty Liver Disease ...

  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. Liver angioscintigraphy: clinical applications.

    Science.gov (United States)

    Dragoteanu, Mircea; Cotul, Sabin O; Pîgleşan, Cecilia; Tamaş, Stefan

    2004-03-01

    Liver angioscintigraphy (LAS) is a radio-isotope method for the investigation of liver perfusion and its alteration in various hepatic diseases. It measures the arterial and portal venous fractions of total liver blood flow. The percentage of liver blood flow supplied by hepatic artery is estimated mathematically by the hepatic perfusion index (HPI), normally between 25 % and 40 %. The decrease of portal blood flow in liver cirrhosis is compensated ("buffer" mechanisms) by increased arterial supply, with higher HPI value. For a patient with chronic liver disease, HPI over 50% suggests arterialization of hepatic perfusion, guiding the diagnose to liver cirrhosis. Splenic curve is completing the diagnostic information of the hepatic curve. Corroborated with per rectal scintigraphy and liver SPECT, LAS offers a good hemodynamic staging of chronic inflammatory liver diseases. Malignant tumors (primitive or metastases) increase the arterial supply of the liver and decrease the portal flow, HPI being over 50% (currently 65 % - 90 %). Benign tumors do not change portal/arterial liver blood flow ratio. SPECT or non-scintigraphic morphological investigations increase the diagnostic value of LAS for primitive liver tumors. Liver cancer occurring on cirrhosis is a limitative factor for LAS. Hepatic metastases increase the arterial perfusion (and HPI value) very quickly, before their size allows morphologic imaging diagnosis. LAS is therefore an early method to diagnose liver metastases being especially used in colorectal cancer. Other clinical applications of LAS are: follow up of liver toxicity of drugs, evaluation of portal vein permeability, post surgery follow up of the liver tumor patients. PMID:15054528

  4. Iron and Liver Diseases

    OpenAIRE

    Fargion, Silvia; Mattioli, Michela; Fracanzani, Anna Ludovica; Fiorelli, Gemino

    2000-01-01

    A mild to moderate iron excess is found in patients with liver diseases apparently unrelated to genetic hemochromatosis. Iron appears to affect the natural history of hepatitis C virus-related chronic liver diseases, alcoholic liver disease and nonalcoholic steatohepatitis by leading to a more severe fibrosis and thus aiding the evolution to cirrhosis.Ahigher frequency of mutations of the HFE gene, the gene responsible for hereditary hemochromatosis, is found in patients with liver diseases a...

  5. MedlinePlus: Liver Transplantation

    Science.gov (United States)

    ... End-Stage Liver Disease (PELD) (United Network for Organ Sharing) - PDF Specifics Living Donor Liver Transplantation (American Society of Transplantation) - PDF Images Liver transplant - slideshow Available in Spanish Statistics and Research U.S. Hospitals with Liver Transplant Centers ( ...

  6. About the Operation: Liver Transplant

    Science.gov (United States)

    ... There are two very different surgical approaches to liver transplantation: the orthotopic and the heterotopic approach, both of ... liver to the intestines. Heterotopic Approach . In heterotopic liver transplantation, the recipient's liver is left in place and ...

  7. Chimeric mice with a humanized liver as an animal model of troglitazone-induced liver injury.

    Science.gov (United States)

    Kakuni, Masakazu; Morita, Mayu; Matsuo, Kentaro; Katoh, Yumiko; Nakajima, Miki; Tateno, Chise; Yokoi, Tsuyoshi

    2012-10-01

    Troglitazone (Tro) is a thiazolidinedione antidiabetic drug that was withdrawn from the market due to its association with idiosyncratic severe liver injury. Tro has never induced liver injury in experimental animals in vivo. It was assumed that the species differences between human and experimental animals in the pharmaco- or toxicokinetics of Tro might be associated with these observations. In this study, we investigated whether a chimeric mouse with a humanized liver that we previously established, whose replacement index with human hepatocytes is up to 92% can reproduce Tro-induced liver injury. When the chimeric mice were orally administered Tro for 14 or 23 days (1000mg/kg/day), serum alanine aminotransferase (ALT) was significantly increased by 2.1- and 3.6-fold, respectively. Co-administration of l-buthionine sulfoximine (10mM in drinking water), an inhibitor of glutathione (GSH) synthesis, unexpectedly prevented the Tro-dependent increase of ALT, which suggests that the GSH scavenging pathway will not be involved in Tro-induced liver injury. To elucidate the mechanism of the onset of liver injury, hepatic GSH content, the level of oxidative stress markers and phase I and phase II drug metabolizing enzymes were determined. However, these factors were not associated with Tro-induced liver injury. An immune-mediated reaction may be associated with Tro-induced liver toxicity in vivo, because the chimeric mouse is derived from an immunodeficient SCID mouse. In conclusion, we successfully reproduced Tro-induced liver injury using chimeric mice with a humanized liver, which provides a new animal model for studying idiosyncratic drug-induced liver injury.

  8. Cell Therapies for Liver Diseases

    Science.gov (United States)

    Yu, Yue; Fisher, James E.; Lillegard, Joseph B.; Rodysill, Brian; Amiot, Bruce; Nyberg, Scott L.

    2011-01-01

    Cell therapies, which include bioartificial liver support and hepatocyte transplantation, have emerged as potential treatments for a variety of liver diseases. Acute liver failure (ALF), acute-on-chronic liver failure, and inherited metabolic liver diseases are examples of liver diseases that have been successfully treated with cell therapies at centers around the world. Cell therapies also have the potential for wide application in other liver diseases, including non-inherited liver diseases and liver cancer, and in improving the success of liver transplantation. Here we briefly summarize current concepts of cell therapy for liver diseases. PMID:22140063

  9. 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.

  10. 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.

  11. 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

  12. 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-

  13. 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.

  14. Liver and spleen volume variations in patients with hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Peng Liu; Peng Li; Wen He; Li-in Zhao

    2009-01-01

    AIM: To study the liver and spleen volume variations in hepatic fibrosis patients at different histopathological stages.METHODS: Multidetector computed tomography (MDCT) scan was performed in 85 hepatic fibrosis patients. Liver volume (LV) and spleen volume (SV) were measured. Fifteen healthy individuals served as a control group (S0). The patients were divided into stage 1 (S1) group ( n = 34), stage 2 (S2) group ( n = 25), stage 3 (S3) group ( n = 16), and stage 4 (S4)group ( n = 10) according to their histopathological stage of liver fibrosis.RESULTS: The LV and standard LV(SLV)had a tendency to increase with the severity of fibrosis, but no statistical difference was observed in the 5 groups (LV: F = 0.245, P = 0.912; SLV: F = 1.902,P = 0.116). The SV was gradually increased with the severity of fibrosis, and a statistically significant difference in SV was observed among the 5 groups( P < 0.01). The LV/SV ratio and SLV/SV ratio were gradually decreased with the aggravation of hepatic fibrosis, and statistically significant differences in both LV/SV and SLV/SV were found among the 5 groups ( P< 0.01).CONCLUSION: The absence of obvious LV reduction in patients with chronic liver disease may be a morphological index of patients without liver cirrhosis. The SV is related to the severity of fibrosis, and the spleen of patients with advanced fibrosis is enlarged evidently. The LV/SV ratio and SLV/SV ratio are of a significant clinical value in the diagnosis of advanced liver fibrosis.

  15. 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.

  16. The effect of Zhage reduced-fat teabags on morphological changes of the experimental nonalcoholic fatty liver disease in rats%楂葛降脂袋泡茶剂对非酒精性脂肪肝大鼠肝脏形态学改变的影响

    Institute of Scientific and Technical Information of China (English)

    黄孟君; 曹永常; 周薪蓓; 余敏; 李俊贤; 姚军; 余红运

    2011-01-01

    目的:观察楂葛降脂袋泡茶剂对实验性非酒精性脂肪肝肝脏形态学改变的影响,为临床治疗非酒精性脂肪肝提供实验依据.方法:采用高脂饮食喂饲大鼠复制脂肪肝模型,实验分组为模型组、降脂通络组和楂葛降脂袋泡茶剂高、中、低剂量组和正常对照组.以楂葛降脂袋泡茶剂高、中、低剂量和降脂通络软胶囊进行干预,各组大鼠肝脏取材,常规HE染色,光镜观察.结果:模型组均可见弥漫性肝细胞脂肪变性,主要为大泡性脂肪变性,也有部分小泡性脂肪变性,并可见大量炎性细胞浸润;楂葛降脂袋泡茶剂组为正常肝组织.仅高倍镜下可见少量肝细胞有小空泡样变.结论:楂葛降脂袋泡茶剂对非酒精性脂肪性肝病有较好的预防和治疗作用.可在一定程度上防止肝脏脂肪过度沉积,改善肝功能,改善肝细胞脂肪变性、减轻肝组织炎症.%Objective To eplore the effect of Zhage reduced-fat teabags(ZhaGe) On morphological changes of the experimental nonalcoholic fatty liver disease in rats and provide the experimental basis for the clinical therapy of nonalcoholic fatty liver disease. Methods The animal model of fatty liver was duplicated with high fat diet and was randomly divided into model group, Lipid-lowering tongluo soft capsule group, high dose ZhaGe group, middle dose ZhaGe group, low dose ZhaGe group, and normal control group. All the treatment groups were intervened by its own medicine. Liver tissue was extracted and made HE staining, then observed by optical microscope. Results Model group are visible diffuse hepatic steatosis, mainly for the big bubble sex steatosis, some small bubble sex steatosis, and note the amount of inflammatory cells infiltrating; ZhaGe group for normal liver tissue. At higher magnification, only a small amount of liver cells have small empty bubble kind change.Conclusion Zhage reduced-fat teabags to nonalcoholic fatty liver disease sex has good

  17. Acute liver failure and liver transplantation.

    Science.gov (United States)

    Akamatsu, Nobuhisa; Sugawara, Yasuhiko; Kokudo, Norihiro

    2013-08-01

    Acute liver failure (ALF) is defined by the presence of coagulopathy (International Normalized Ratio ≥ 1.5) and hepatic encephalopathy due to severe liver damage in patients without pre-existing liver disease. Although the mortality due to ALF without liver transplantation is over 80%, the survival rates of patients have considerably improved with the advent of liver transplantation, up to 60% to 90% in the last two decades. Recent large studies in Western countries reported 1, 5, and 10-year patient survival rates after liver transplantation for ALF of approximately 80%, 70%, and 65%, respectively. Living donor liver transplantation (LDLT), which has mainly evolved in Asian countries where organ availability from deceased donors is extremely scarce, has also improved the survival rate of ALF patients in these regions. According to recent reports, the overall survival rate of adult ALF patients who underwent LDLT ranges from 60% to 90%. Although there is still controversy regarding the graft type, optimal graft volume, and ethical issues, LDLT has become an established treatment option for ALF in areas where the use of deceased donor organs is severely restricted. PMID:25343108

  18. 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.

  19. Liver and gastrointestinal tract

    International Nuclear Information System (INIS)

    Liver is often a site of a variety of diseases. A palpable liver during a routine clinical examination is an important finding and requires further investigations. The availability of non-invasive liver imaging procedures using nuclear, ultrasound, CT (and now MRI) techniques have immensely enhanced diagnostic accuracy in liver diseases. In this Chapter, a detailed description of routinely practised nuclear medicine procedures related to liver is given. Brief reference is also made to other imaging techniques, particularly ultrasonography, only for the purposes of comparison. Most of the information is based on our own clinical experience of past 30 years

  20. 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.

  1. 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.

  2. Trichloroethylene exposure aggravates behavioral abnormalities in mice that are deficient in superoxide dismutase.

    Science.gov (United States)

    Otsuki, Noriyuki; Homma, Takujiro; Fujiwara, Hiroki; Kaneko, Kenya; Hozumi, Yasukazu; Shichiri, Mototada; Takashima, Mizuki; Ito, Junitsu; Konno, Tasuku; Kurahashi, Toshihiro; Yoshida, Yasukazu; Goto, Kaoru; Fujii, Satoshi; Fujii, Junichi

    2016-08-01

    Trichloroethylene (TCE) has been implicated as a causative agent for Parkinson's disease (PD). The administration of TCE to rodents induces neurotoxicity associated with dopaminergic neuron death, and evidence suggests that oxidative stress as a major player in the progression of PD. Here we report on TCE-induced behavioral abnormality in mice that are deficient in superoxide dismutase 1 (SOD1). Wild-type (WT) and SOD1-deficient (Sod1(-/-)) mice were intraperitoneally administered TCE (500 mg/kg) over a period of 4 weeks. Although the TCE-administrated Sod1(-/-) mice showed marked abnormal motor behavior, no significant differences were observed among the experimental groups by biochemical and histopathological analyses. However, treating mouse neuroblastoma-derived NB2a cells with TCE resulted in the down regulation of the SOD1 protein and elevated oxidative stress under conditions where SOD1 production was suppressed. Taken together, these data indicate that SOD1 plays a pivotal role in protecting motor neuron function against TCE toxicity. PMID:27166294

  3. Telomeres, NAFLD and Chronic Liver Disease.

    Science.gov (United States)

    Donati, Benedetta; Valenti, Luca

    2016-01-01

    Telomeres consist of repeat DNA sequences located at the terminal portion of chromosomes that shorten during mitosis, protecting the tips of chromosomes. During chronic degenerative conditions associated with high cell replication rate, progressive telomere attrition is accentuated, favoring senescence and genomic instability. Several lines of evidence suggest that this process is involved in liver disease progression: (a) telomere shortening and alterations in the expression of proteins protecting the telomere are associated with cirrhosis and hepatocellular carcinoma; (b) advanced liver damage is a feature of a spectrum of genetic diseases impairing telomere function, and inactivating germline mutations in the telomerase complex (including human Telomerase Reverse Transcriptase (hTERT) and human Telomerase RNA Component (hTERC)) are enriched in cirrhotic patients independently of the etiology; and (c) experimental models suggest that telomerase protects from liver fibrosis progression. Conversely, reactivation of telomerase occurs during hepatocarcinogenesis, allowing the immortalization of the neoplastic clone. The role of telomere attrition may be particularly relevant in the progression of nonalcoholic fatty liver, an emerging cause of advanced liver disease. Modulation of telomerase or shelterins may be exploited to prevent liver disease progression, and to define specific treatments for different stages of liver disease. PMID:26999107

  4. 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

  5. Experimental study of Ganpitiaobu Fang on immunological liver injury in mice%肝脾调补方对小鼠免疫性肝损伤的防护作用

    Institute of Scientific and Technical Information of China (English)

    阮连国; 张妍; 朱清静

    2012-01-01

    目的:观察中药肝脾调补方对小鼠免疫性肝损伤的防护作用并探讨其药理学机制.方法:采用卡介苗(BCG)+脂多糖(LPS)建立小鼠免疫性肝损伤模型,通过肝脾调补方高、中、低剂量灌胃,观察肝脾调补方对各组小鼠血清丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)及肝组织匀浆超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)水平的影响;ELISA法检测肿瘤坏死因子-α(TNF-α)的变化.结果:肝脾调补方可明显降低免疫性肝损伤小鼠血清中ALT、AST、TNF-α水平;减少肝组织匀浆的MDA含量,升高肝匀浆SOD、GSH-Px含量.结论:肝脾调补方对BCG+LPS尾静脉注射造成的小鼠免疫性肝损伤有明显的防护作用,其作用与抗脂质过氧化有关.%Objective: To study the effects of Ganpitiaobu Fang in protecting immunity hepatic injury induced by bacille calmette Guerin (BCG) and lipopolyhepatic (LPS) in mice and study on its pharmacological mechanism. Methods: The immunological liver injury rat model was produced by intraperitonealitonealinjection with BCG plus LPS. Sixty mice divied into control group , model group, low dose group, middle dose group and high dose group randomly. The levels of alanine am intransferase (ALT) , aspartate an inotransferase (AST) , tumor necrosis factor-a (TNF-α) in blood plasma and super oxide dismutase (SOD ) of liver homogenate malondialdehyde ( MDA ) , Glutathione peroxidase ( GSH-PX) of the five groups were examined. Results: Ganpitiaobu Fang significantly reduced immunological liver injury in mice by reducing serum ALT, AST, TNF-alpha level; reducing MDA content of liver homogenate and elevated SOD, GSH-PX of contents liver homogenate. Conclusion: Ganpitiaobu Fang can obviously protect immunologicalinjury to liver in rats. Its role mechanism is related with anti-lipid peroxidation.

  6. [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.

  7. Liver transplantation in India.

    Science.gov (United States)

    Narasimhan, Gomathy; Kota, Venugopal; Rela, Mohamed

    2016-07-01

    Liver transplantation as an established form of treatment for end-stage liver disease has gained acceptance in India over the last 10 years. Liver transplantation in India has unique features that have contributed to the growth of both deceased donor and living donor transplantations of which living donor currently dominates the picture. Living donor contributes to 80% and deceased donor to 20% of the liver transplants currently performed in India. The majority of these transplants are performed within the private sector with public sector hospitals lagging behind significantly. This article gives an overview of the evolution of liver transplantation in India and the potential future challenges. Liver Transplantation 22 1019-1024 2016 AASLD. PMID:27082718

  8. 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.

  9. Differential proteomic analysis of STAT6 knockout mice reveals new regulatory function in liver lipid homeostasis.

    Science.gov (United States)

    Iff, Joël; Wang, Wei; Sajic, Tatjana; Oudry, Nathalie; Gueneau, Estelle; Hopfgartner, Gérard; Varesio, Emmanuel; Szanto, Ildiko

    2009-10-01

    Increased inflammatory signaling is a key feature of metabolic disorders. In this context, the role of increased pro-inflammatory signals has been extensively studied. By contrast, no efforts have been dedicated to study the contrasting scenario: the attenuation of anti-inflammatory signals and their role in metabolic homeostasis. IL-4 and IL-13 are anti-inflammatory cytokines signaling through the Signal Transducer and Activator of Transcription 6 (STAT6). Our study was aimed at evaluating the lack of STAT6 signaling on liver homeostasis. To this end we analyzed the liver proteome of wild type and STAT6 knock-out mice using 2D nanoscale LC-MS/MS with iTRAQ labeling technique. The coordinated changes in proteins identified by this quantitative proteome analysis indicated disturbed lipid homeostasis and a state of hepatocellular stress. Most significantly, the expression of the liver fatty acid binding protein (FABP1) was increased in the knock-out mice. In line with the elevated FABP1 expression we found latent liver lipid accumulation in the STAT6-deficient mice which was further aggravated when mice were challenged by a high fat diet. In conclusion, our study revealed a so far uncharacterized role for STAT6 in regulating liver lipid homeostasis and demonstrates the importance of anti-inflammatory signaling in the defense against the development of liver steatosis. PMID:19663508

  10. 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

  11. A higher oxidative status accelerates senescence and aggravates age-dependent disorders in SAMP strains of mice.

    Science.gov (United States)

    Hosokawa, Masanori

    2002-11-01

    The SAM strain of mice is actually a group of related inbred strains consisting of series of SAMP (accelerated senescence-prone, short-lived) and SAMR (accelerated senescence-resistant, longer-lived) strains. Comparing with the SAMR strains, the SAMP strains of mice show a more accelerated senescence process, shorter lifespan, and an earlier onset and more rapid progress of age-associated pathological phenotypes similar to several geriatric disorders observed in humans, including senile osteoporosis, degenerative joint disease, age-related deficits in learning and memory, olfactory bulb and forebrain atrophy, presbycusis and retinal atrophy, senile amyloidosis, immunosenescence, senile lungs, and diffuse medial thickening of the aorta. The higher oxidative stress observed in the SAMP strains of mice are partly caused by mitochondrial dysfunction, and may be one cause of the senescence acceleration and age-dependent alterations in cell structure and function, including neuronal cell degeneration. This senescence acceleration is also observed during senescence/crisis in cultures of isolated fibroblast-like cells from SAMP strains of mice, and was associated with a hyperoxidative status. These observations suggest that the SAM strains are useful tools in the attempt to understand the mechanisms of age-dependent degeneration of cells and tissues, and their aggravation, and to develop clinical interventions. PMID:12470893

  12. 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.

  13. 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.

  14. 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.

  15. Epiplakin deficiency aggravates murine caerulein-induced acute pancreatitis and favors the formation of acinar keratin granules.

    Directory of Open Access Journals (Sweden)

    Karl L Wögenstein

    Full Text Available Epiplakin, a member of the plakin protein family, is exclusively expressed in epithelial tissues and was shown to bind to keratins. Epiplakin-deficient (EPPK-/- mice showed no obvious spontaneous phenotype, however, EPPK-/- keratinocytes displayed faster keratin network breakdown in response to stress. The role of epiplakin in pancreas, a tissue with abundant keratin expression, was not yet known. We analyzed epiplakin's expression in healthy and inflamed pancreatic tissue and compared wild-type and EPPK-/- mice during caerulein-induced acute pancreatitis. We found that epiplakin was expressed primarily in ductal cells of the pancreas and colocalized with apicolateral keratin bundles in murine pancreatic acinar cells. Epiplakin's diffuse subcellular localization in keratin filament-free acini of K8-deficient mice indicated that its filament-associated localization in acinar cells completely depends on its binding partner keratin. During acute pancreatitis, epiplakin was upregulated in acinar cells and its redistribution closely paralleled keratin reorganization. EPPK-/- mice suffered from aggravated pancreatitis but showed no obvious regeneration phenotype. At the most severe stage of the disease, EPPK-/- acinar cells displayed more keratin aggregates than those of wild-type mice. Our data propose epiplakin to be a protective protein during acute pancreatitis, and that its loss causes impaired disease-associated keratin reorganization.

  16. Partial Beclin 1 silencing aggravates doxorubicin- and Fas-induced apoptosis in HepG2 cells

    Institute of Scientific and Technical Information of China (English)

    Fanny Daniel; Agnès Legrand; Dominique Pessayre; Nathalie Vadrot; Véronique Descatoire; Dominique Bernuau

    2006-01-01

    AIM: To investigate the role of Beclin 1 on the susceptibility of HepG2 cells to undergo apoptosis after anti-Fas antibody or doxorubicin treatment.METHODS: Beclin 1 silencing was achieved using RNA interference. DNA ploidy, the percentage of apoptotic cells and the mitochondrial membrane potential were assessed by flow cytometry. Levels of Beclin 1, Bcl-XL and cytochrome c, and the cleavage of poly (ADP-ribose)polymerase (PARP) were assayed by using Western blots.RESULTS: Beclin 1 expression decreased by 75% 72 h after Beclin 1 siRNA transfection. Partial Beclin 1 silencing significantly increased the percentage of subG1 cells 24 and 40 h after treatment with doxorubicin or anti-Fas antibody, respectively, and this potentiation was abrogated by treatment with a pan-caspase inhibitor.Partial Beclin 1 silencing also increased PARP cleavage,mitochondrial membrane depolarization and cytosolic cytochrome c. The pro-apoptotic consequences of partial Beclin 1 silencing were not associated with a decline in Bcl-XL expression.CONCLUSION: Partial Beclin 1 silencing aggravates mitochondrial permeabilization and apoptosis in HepG2 cells treated with an anti-Fas antibody or with doxorubicin.

  17. 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.

  18. 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

    2016-01-01

    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. PMID:27264309

  19. 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

  20. Blockade of Wnt/β-Catenin Pathway Aggravated Silica-Induced Lung Inflammation through Tregs Regulation on Th Immune Responses

    Directory of Open Access Journals (Sweden)

    Wujing Dai

    2016-01-01

    Full Text Available CD4+ T cells play an important role in regulating silica-induced inflammation and fibrosis. Recent studies showed that Wnt/β-catenin pathway could modulate the function and the differentiation of CD4+ T cells. Therefore, Wnt/β-catenin pathway may participate in the development and progress of silicosis. To investigate the role of Wnt/β-catenin pathway, we used lentivirus expressing β-catenin shRNA to block the Wnt/β-catenin pathway by intratracheal instillation to the mice model of silicosis. Treatment of lentivirus could significantly aggravate the silica-induced lung inflammation and attenuated the fibrosis at the late stage. By analyzing CD4+ T cells, we found that blockade of Wnt/β-catenin pathway suppressed regulatory T cells (Tregs. Reciprocally, enhanced Th17 response was responsible for the further accumulation of neutrophils and production of proinflammatory cytokines. In addition, blockade of Wnt/β-catenin pathway delayed the Th1/Th2 polarization by inhibiting Tregs and Th2 response. These results indicated that Wnt/β-catenin pathway could regulate Tregs to modulate Th immune response, which finally altered the pathological character of silicosis. Our study suggested that Wnt/β-catenin pathway might be a potential target to treat the silica-induced inflammation and fibrosis.

  1. Make-up improves the quality of life of acne patients without aggravating acne eruptions during treatments.

    Science.gov (United States)

    Hayashi, Nobukazu; Imori, Mizuho; Yanagisawa, Midori; Seto, Yoko; Nagata, Osamu; Kawashima, Makoto

    2005-01-01

    Boehncke et al. suggested that decorative cosmetics can improve the quality of life (QOL) of skin diseases. But dermatologists sometimes discourage female acne patients from applying make-up since decorative cosmetics are considered one of the aggravating factors for acne eruptions. The purpose of this study is to assess whether make-up application interferes with acne treatments and how QOL changes when the make-up items are designed for acne patients and used in order to disguise acne eruptions. Eighteen female acne patients were trained by a make-up artist and advised to apply acne-designed basic and decorative cosmetics for 2 to 4 weeks while their acne was appropriately treated. The acne-severity and QOL of patients were assessed before and after the study. The results revealed that the number of acne eruptions decreased even though patients were applying make-up. The QOL scores of Skindex-16, GHQ30 and anxiety state index greatly improved. Our results suggest that dermatologists should encourage acne patients to utilize appropriate make-up to improve their QOL. PMID:16048760

  2. Robotic liver surgery.

    Science.gov (United States)

    Leung, Universe; Fong, Yuman

    2014-10-01

    Robotic surgery is an evolving technology that has been successfully applied to a number of surgical specialties, but its use in liver surgery has so far been limited. In this review article we discuss the challenges of minimally invasive liver surgery, the pros and cons of robotics, the evolution of medical robots, and the potentials in applying this technology to liver surgery. The current data in the literature are also presented. PMID:25392840

  3. MANAGEMENT OF LIVER TRAUMA

    OpenAIRE

    Dova Subba; Mallapraggada Rama Chandra; Erabatti

    2016-01-01

    AIM To estimate the incidence of Liver Trauma injuries and grade their severity of injury. To assess the factors responsible for morbidity and mortality after Liver Trauma. To study the postoperative complications and the management of Liver Trauma. MATERIALS AND METHODS The present prospective study was conducted on 100 patients who were admitted to Department of General Surgery for treatment who were managed operatively or non-operatively for abdominal trauma and h...

  4. 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...

  5. 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.

  6. Liver transplant - series (image)

    Science.gov (United States)

    ... depending on the degree of illness. After liver transplantation, patients must take immunosuppressive medications for the rest of their lives to prevent immune rejection of the transplanted organ.

  7. 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

  8. Experimental study on mechanism of graft injury of small-for-size liver transplantation in miniature pigs%小体积肝移植损伤机制的实验观察

    Institute of Scientific and Technical Information of China (English)

    冷建军; 董家鸿; 韩本立

    2009-01-01

    目的 探讨小体积移植肝损伤机制.方法 采用肝周骨骼化的去神经解剖、肝切除和原位灌注建立巴马小型猪不同移植量肝移植模型.分为3组(n=5):(1)A组:原位肝移植组;(2)B组:右半肝供肝肝部分移植组;(3)C组:右中叶和尾状叶供肝部分肝移植组.移植后观察动物7 d存活率,动态监测门静脉压(PVP)、门静脉血流量(PBF)以及移植肝组织学病理改变.结果 巴马小型猪不同移植量肝移植7 d存活率分别为:A组100%(5/5);B组100%(5/5)和C组20%(1/5).C组移植肝复流后PVP立即升高,高峰达(28.6±2.07)mm Hg,复流后1 h单位肝组织PBF达(3.56±0.11)ml·min-1·g-1.C组移植肝组织病理改变严重,包括肝窦淤血、出血,肝细胞气球样变或肝细胞坏死,内皮细胞脱落,狄氏间隙增宽或消失以及明显的细胞凋亡.结论 小体积肝移植中门静脉过度灌流和急性门静脉高压是移植肝的主要病因学机制.%Objective To elucidate the mechanisms of graft injury in small-for-size liver transplantation. Methods Animal models were established with skeletonized and denervated anatomic para-hepatic dissection, hepatectomy and perfusion in situ. Chinese Bama miniature pigs were divided into three groups (n=5): Group A, liver transplantation; Group B, partial liver transplantation with right hemi-liver graft and Group C, liver transplantation with right median and caudate lobe graft. Animals were followed for 7 days with regards to survival, dynamical portal venous pressure (PVP), portal blood flow (PBF) and graft histopathological examination. Results Animal survivals were as follows: Group A, 5/5, Group B, 5/5 and Group C, 1/5. PVP rose immediately after reperfusion. PVP in Group C peaked to 28.6±2.07 mm Hg. Portal blood flow (PBF) measured by CDFI showed that the index of PBF per gram liver tissue reached 3.56±showed that severe pathological changes occurred in small-for-size grafts, including sinusoidal congestion, hemorrhage

  9. 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...

  10. Liver transplantation for polycystic liver and massive hepatomegaly

    OpenAIRE

    Gruttadauria, Salvatore; Di Francesco, Fabrizio; Gridelli, Bruno

    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 ...

  11. 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

  12. Modeling the mechanical properties of liver fibrosis in rats.

    Science.gov (United States)

    Zhu, Ying; Chen, Xin; Zhang, Xinyu; Chen, Siping; Shen, Yuanyuan; Song, Liang

    2016-06-14

    The progression of liver fibrosis changes the biomechanical properties of liver tissue. This study characterized and compared different liver fibrosis stages in rats in terms of viscoelasticity. Three viscoelastic models, the Voigt, Maxwell, and Zener models, were applied to experimental data from rheometer tests and then the elasticity and viscosity were estimated for each fibrosis stage. The study found that both elasticity and viscosity are correlated with the various stages of liver fibrosis. The study revealed that the Zener model is the optimal model for describing the mechanical properties of each fibrosis stage, but there is no significant difference between the Zener and Voigt models in their performance on liver fibrosis staging. Therefore the Voigt model can still be effectively used for liver fibrosis grading. PMID:27017300

  13. About the Operation: Liver Transplant

    Science.gov (United States)

    ... Heart/Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Liver Transplant There are two very different surgical approaches to liver transplantation: the orthotopic and the heterotopic approach, both of ...

  14. 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

  15. Living Donor Liver Transplantation

    Science.gov (United States)

    ... What are Some Benefits of a Living-donor Liver Transplant? In the U.S., more than 17,500 patients ... 1,700 patients die each year while waiting. Liver transplants are given to patients on the basis of ...

  16. Liver (Hepatocellular) Cancer Prevention

    Science.gov (United States)

    ... This may lead to liver cancer. Blood banks test all donated blood for hepatitis B, which greatly lowers the risk of getting the ... This may lead to liver cancer. Blood banks test all donated blood for hepatitis C, which ... infected with hepatitis B. It is caused by hepatitis D virus (HDV) ...

  17. 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...

  18. 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

  19. 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.

  20. 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

  1. Accreditation not Aggravation

    Science.gov (United States)

    Moss, Cath; Archer, Judith

    2014-01-01

    This paper describes an action research project that investigated a range of activities to improve learners' mathematical communication skills. It also gives details of a subsequent case study that illustrates how technology can provide a means of overcoming some of the difficulties learners and tutors face in communicating about numeracy, while…

  2. 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

  3. 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.

  4. 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...

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. Glucagon-mediated impairments in hepatic and peripheral tissue nutrient disposal are not aggravated by increased lipid availability

    OpenAIRE

    Chen, Sheng-Song; Santomango, Tammy S.; Williams, Phillip E.; Lacy, D. Brooks; McGuinness, Owen P.

    2009-01-01

    Glucose, fat, and glucagon availability are increased in diabetes. The normal response of the liver to chronic increases in glucose availability is to adapt to become a marked consumer of glucose. Yet this fails to occur in diabetes. The aim was to determine whether increased glucagon and lipid interact to impair the adaptation to increased glucose availability. Chronically catheterized well controlled depancreatized conscious dogs (n = 21) received 3 days of continuous parenteral nutrition (...

  13. 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.

  14. Ovarian senescence increases liver fibrosis in humans and zebrafish with steatosis.

    OpenAIRE

    Elena Turola; Salvatore Petta; Ester Vanni; Fabiola Milosa; Luca Valenti; Rosina Critelli; Luca Miele; Livia Maccio; Vincenza Calvaruso; Fracanzani, Anna L.; Marcello Bianchini; Nazarena Raos; Elisabetta Bugianesi; Serena Mercorella; Marisa Di Giovanni

    2015-01-01

    ABSTRACT Contrasting data exist on the effect of gender and menopause on the susceptibility, development and liver damage progression in non-alcoholic fatty liver disease (NAFLD). Our aim was to assess whether menopause is associated with the severity of liver fibrosis in individuals with NAFLD and to explore the issue of ovarian senescence in experimental liver steatosis in zebrafish. In 244 females and age-matched males with biopsy-proven NAFLD, we assessed anthropometric, biochemical and m...

  15. 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.

  16. Rat liver insulin receptor

    International Nuclear Information System (INIS)

    Using insulin affinity chromatography, the authors have isolated highly purified insulin receptor from rat liver. When evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions, the rat liver receptor contained the M/sub r/ 125,000 α-subunit, the M/sub r/ 90,000 β-subunit, and varying proportions of the M/sub r/ 45,000 β'-subunit. The specific insulin binding of the purified receptor was 25-30 μg of 125I-insulin/mg of protein, and the receptor underwent insulin-dependent autophosphorylation. Rat liver and human placental receptors differ from each other in several functional aspects: (1) the adsorption-desorption behavior from four insulin affinity columns indicated that the rat liver receptor binds less firmly to immobilized ligands; (2) the 125I-insulin binding affinity of the rat liver receptor is lower than that of the placental receptor; (3) partial reduction of the rat liver receptor with dithiothreitol increases its insulin binding affinity whereas the binding affinity of the placental receptor is unchanged; (4) at optimal insulin concentration, rat liver receptor autophosphorylation is stimulated 25-50-fold whereas the placental receptor is stimulated only 4-6-fold. Conversion of the β-subunit to β' by proteolysis is a major problem that occurs during exposure of the receptor to the pH 5.0 buffer used to elute the insulin affinity column. Proteolytic destruction and the accompanying loss of insulin-dependent autophosphorylation can be substantially reduced by proteolysis inhibitors. In summary, rat liver and human placental receptors differ functionally in both α- and β-subunits. Insulin binding to the α-subunit of the purified rat liver receptor communicates a signal that activates the β-subunit; however, major proteolytic destruction of the β-subunit does not affect insulin binding to the α-subunit

  17. 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.

  18. [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...

  19. Do We Know What Causes Liver Cancer?

    Science.gov (United States)

    ... TOPICS Document Topics GO » SEE A LIST » Liver cancer risk factors Do we know what causes liver cancer? Can liver cancer be prevented? Previous Topic Liver cancer risk factors Next Topic Can liver cancer be prevented? Do ...

  20. 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

  1. 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.

  2. Anti-Fas mAb-induced apoptosis and cytolysis of airway tissue eosinophils aggravates rather than resolves established inflammation

    Directory of Open Access Journals (Sweden)

    Persson Carl GA

    2005-08-01

    eosinophils progressed into the pro-inflammatory cellular fate of secondary necrosis this may also explain the aggravated inflammation. Our data indicate that Fas receptor mediated eosinophil apoptosis in airway tissues in vivo may cause severe disease exacerbation due to direct cytolysis and secondary necrosis of eosinophils.

  3. Living donor liver transplantation for patients with alcoholic liver disease

    OpenAIRE

    Park, Yo-Han; Hwang, Shin; Ahn, Chul-Soo; Kim, Ki-Hun; Moon, Deok-Bog; Ha, Tae-Yong; Song, Gi-Won; Jung, Dong-Hwan; Park, Gil-Chun; Namgoong, Jung-Man; Park, Hyung-Woo; Park, Chun-Soo; Kang, Sung-Hwa; Jung, Bo-Hyeon; Lee, Sung-Gyu

    2013-01-01

    Backgrounds/Aims Since most transplantation studies for alcoholic liver disease (ALD) were performed on deceased donor liver transplantation, little was known following living donor liver transplantation (LDLT). Methods The clinical outcome of 18 ALD patients who underwent LDLT from Febraury 1997 to December 2004 in a large-volume liver transplantation center was assessed retrospectively. Results The model for end-stage liver disease score was 23±11, and mean pretransplant abstinence period w...

  4. 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.

  5. Living Related Liver Transplantation

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Living Related Liver Transplantation (LRLT)is a new strategy, which offers the option of a lifesaving procedure to patients suffering from end - stage liver disease, and the experience indicates that the results are better than cadaveric liver transplantation. It promises to decrease the waiting time for liver transplantation significantly and to reduce the number of patients dying on the waiting list. The selection of a suitable donor and the techniques of operation are of paramount importance for LRLT to minimize the risk for the recipient and the donor, and achieve better outcome for patient. 1 -year recipient survival rate of LRLT is over 90% and 5 -year recipient survival rate of LRLT is about 80%. LRLT has been becoming standard and normal operation in many western transplant centers.

  6. 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.

  7. Research Areas: Liver Disease

    Science.gov (United States)

    ... 900 drugs and supplements.​​ Recent discoveries from NIDDK research include: New medication shows promise against liver fibrosis ... linked to biliary atresia in newborn animals Support Research NIDDK invests in basic, clinical and translational research ...

  8. [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.

  9. 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.......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....

  10. 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.

  11. 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)

  12. 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....

  13. 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...

  14. Antifibrinolytics in liver surgery

    OpenAIRE

    Jalpa Makwana; Saloni Paranjape; Jyotsna Goswami

    2010-01-01

    Hyperfibrinolysis, a known complication of liver surgery and orthotopic liver transplantation (OLT), plays a significant role in blood loss. This fact justifies the use of antifibrinolytic drugs during these procedures. Two groups of drug namely lysine analogues [epsilon aminocaproic acid (EACA) and tranexamic acid (TA)] and serine-protease-inhibitors (aprotinin) are frequently used for this purpose. But uniform data or guidelines on the type of antifibrinolytic drugs to be used, their indica...

  15. 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.

  16. Prognostic Value of Gc-Globulin in Chinese Patients with Acute-On-Chronic Hepatitis B Liver Failure

    International Nuclear Information System (INIS)

    Objective: To determine dynamic Gc-globulin level change in Acute-on-Chronic Hepatitis B Liver Failure (ACHBLF) patients, and evaluate the prognostic value of Gc-globulin. Study Design: An analytical study. Place and Duration of Study: The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China, from January 2010 to December 2012. Methodology: A total of 54 consecutive Chinese ACHBLF patients and 30 healthy volunteers as controls were recruited from 2010 to 2012. The patients were divided into improved group and aggravated group. Gc-globulin levels were determined in both groups and mean values compared with significance at p < 0.05. Cut-off value was also determined. Results: The Gc-globulin level was significantly decreased in ACHBLF patients (p < 0.001). Gc-globulin levels were significantly higher in improved patients than in aggravated patients, and a 215 mg/L cut-off value carried the best prognostic information. On longitudinal observations, Gc-globulin gradually elevated in improved groups. However, in aggravated groups, the Gc-globulin levels were always below normal levels and no significant change was observed before or after the treatment (p > 0.05). Conclusion: Gc-globulin monitoring offers a rapid and accurate method to estimate treatment outcomes on admission and an effective temporal indicator of curative effects in ACHBLF patients at an optimal cut-off value of 215 mg/L. (author)

  17. 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.

  18. Liver transplantation in Ireland.

    Science.gov (United States)

    Iqbal, Masood; Elrayah, Elgaily A; Traynor, Oscar; McCormick, P Aiden

    2016-07-01

    The Irish National Liver Transplant program commenced in 1993 in St. Vincent's University Hospital in Dublin. It is an adult-only program and is the only liver transplant program in Ireland. Pediatric recipients are referred to King's College Hospital in the United Kingdom. To date, almost 1000 adult liver transplants have been performed. Current 1-year patient survival is 93%, and 5-year survival is 79%. The program is fully funded by the government health service. There is a close collaboration with the United Kingdom Organ Donation and Transplant Directorate, and there is an arrangement for organ sharing for super-urgent transplants. Traditionally, organ donation rates have been high in Ireland. However, demand for liver transplant has increased over the past 20 years, and waiting lists are now lengthening. Deceased cardiac death donation is now being considered, but there are no plans for living related donor liver transplant. Donor coordinators have recently been appointed to the major hospitals in Ireland, and it is hoped that this initiative will lead to an increase in organ donation rates. Liver Transplantation 22 1014-1018 2016 AASLD. PMID:27065358

  19. 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.

  20. 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.

  1. Percutaneous Cryoablation for Liver Cancer

    OpenAIRE

    Niu, Li-Zhi; Li, Jia-Liang; Xu, Ke-Cheng

    2014-01-01

    Based on the primary tumor site, liver cancer can be divided into two categories: (1) primary liver cancer and (2) metastatic cancer to the liver from a distant primary site. Guided cryoablation via many imaging methods induces iceball formation and tumor necrosisand is an attractive option for treating unresectable hepatocellular carcinoma (HCC) and metastatic liver cancer. There are several advantages to using cryoablation for the treatment of liver cancer: it can be performed percutaneousl...

  2. The Liver in Critical Illness.

    Science.gov (United States)

    Damm, Tessa W; Kramer, David J

    2016-07-01

    Caring for critically ill patients with acute and/or chronic liver dysfunction poses a unique challenge. Proper resuscitation and early consideration for transfer to liver transplant centers have resulted in improved outcomes. Liver support devices and cellular models have not yet shown mortality benefit, but they hold promise in the critical care of patients with liver disease. This article reviews pertinent anatomic and physiologic considerations of the liver in critical illness, followed by a selective review of associated organ dysfunction. PMID:27339681

  3. 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

  4. 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...

  5. Excellent survival after liver transplantation for isolated polycystic liver disease: an European Liver Transplant Registry study

    NARCIS (Netherlands)

    Keimpema, L. van; Nevens, F.; Adam, R.; Porte, R.J.; Fikatas, P.; Becker, T.; Kirkegaard, P.; Metselaar, H.J.; Drenth, J.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

  6. 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

  7. Experimental study of three-dimensional contrast-enhanced ultrasonic cholangiography in isolated porcine liver specimens%离体猪肝三维超声胆管造影的实验研究

    Institute of Scientific and Technical Information of China (English)

    许尔蛟; 李凯; 毛仁; 张奥华; 任杰; 廖梅; 苏中振; 郑荣琴

    2010-01-01

    目的 探讨三维超声胆管造影技术显示肝内胆管的可行性.方法 对5个离体猪肝不同肝叶的胆管分别进行插管,经插管注入1:20稀释的SonoVue超声造影剂后进行三维超声造影检查,分别评价可分辨最高胆管分支级别和图像质量,并与X线胆道造影作比较,评价其胆管树形态拟合度.结果 在5个离体猪肝中成功插管14个分叶,最高可显示至第3级分支,最高显示级别为第3、2、1级分支的比例依次为42.9%(6/14)、42.9%(6/14)、14.2%(2/14);图像质量优、中、差的比例依次为21.4%(3/14)、57.2%(8/14)、21.4%(3/14);与X线胆道造影比较,图像拟合度优、中、差的比例依次为42.9%(6/14)、42.9%(6/14)、14.2%(2/14).结论 三维超声胆管造影技术可能是一种显示胆管树解剖结构的全新影像学方法.%Objective To investigate the feasibility of three-dimensional contrast-enhanced ultrasonic cholangiography(3D-CEUSC) in isolated porcine liver specimens.Methods The lobes of 5 isolated porcine livers were taken as scanning units and the lobular bile branches were cannulated.3D-CEUSC was performed after the administration of diluted ultrasonic contrast agents(SonoVue) through the cannula.The images were assessed in term of maximum visualization of branching orders and image quality.The coincidence of morphous was compared between 3D-CEUSC and cholangiagraphy using fluoroscopy.Results Fourteen lobular biliary branches were cannulated successfully in 5 isolated porcine livers.The maximum visualization of branching orders from the third- to first-order branches were 42.9% (6/14) ,42.9% (6/14), 14.2% (2/14) in sequence.The image quality was 21.4% (3/14) graded as well, 57.2% (8/14) as moderate, and 21.4% (3/14) as poor.Compare with cholangiagraphy using fluoroscopy, the coincidence of morphous was 42.9%(6/14) for well,42.9% (6/14) for moderate,and 14.2% (2/14) for poor.Conclusions 3D-CEUSC could be a new imaging method to evaluate the biliary

  8. Themes of liver transplantation.

    Science.gov (United States)

    Starzl, Thomas E; Fung, John J

    2010-06-01

    Liver transplantation was the product of five interlocking themes. These began in 1958-1959 with canine studies of then theoretical hepatotrophic molecules in portal venous blood (Theme I) and with the contemporaneous parallel development of liver and multivisceral transplant models (Theme II). Further Theme I investigations showed that insulin was the principal, although not the only, portal hepatotrophic factor. In addition to resolving long-standing controversies about the pathophysiology of portacaval shunt, the hepatotrophic studies blazed new trails in the regulation of liver size, function, and regeneration. They also targeted inborn metabolic errors (e.g., familial hyperlipoproteinemia) whose palliation by portal diversion presaged definitive correction with liver replacement. Clinical use of the Theme II transplant models depended on multiple drug immunosuppression (Theme III, Immunology), guided by an empirical algorithm of pattern recognition and therapeutic response. Successful liver replacement was first accomplished in 1967 with azathioprine, prednisone, and antilymphoid globulin. With this regimen, the world's longest surviving liver recipient is now 40 years postoperative. Incremental improvements in survival outcome occurred (Theme IV) when azathioprine was replaced by cyclosporine (1979), which was replaced in turn by tacrolimus (1989). However, the biologic meaning of alloengraftment remained enigmatic until multilineage donor leukocyte microchimerism was discovered in 1992 in long-surviving organ recipients. Seminal mechanisms were then identified (clonal exhaustion-deletion and immune ignorance) that linked organ engraftment and the acquired tolerance of bone marrow transplantation and eventually clarified the relationship of transplantation immunology to the immunology of infections, neoplasms, and autoimmune disorders. With this insight, better strategies of immunosuppression have evolved. As liver and other kinds of organ transplantation

  9. 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.

  10. Adenovirus serotype 5 hexon mediates liver gene transfer.

    Science.gov (United States)

    Waddington, Simon N; McVey, John H; Bhella, David; Parker, Alan L; Barker, Kristeen; Atoda, Hideko; Pink, Rebecca; Buckley, Suzanne M K; Greig, Jenny A; Denby, Laura; Custers, Jerome; Morita, Takashi; Francischetti, Ivo M B; Monteiro, Robson Q; Barouch, Dan H; van Rooijen, Nico; Napoli, Claudio; Havenga, Menzo J E; Nicklin, Stuart A; Baker, Andrew H

    2008-02-01

    Adenoviruses are used extensively as gene transfer agents, both experimentally and clinically. However, targeting of liver cells by adenoviruses compromises their potential efficacy. In cell culture, the adenovirus serotype 5 fiber protein engages the coxsackievirus and adenovirus receptor (CAR) to bind cells. Paradoxically, following intravascular delivery, CAR is not used for liver transduction, implicating alternate pathways. Recently, we demonstrated that coagulation factor (F)X directly binds adenovirus leading to liver infection. Here, we show that FX binds to the Ad5 hexon, not fiber, via an interaction between the FX Gla domain and hypervariable regions of the hexon surface. Binding occurs in multiple human adenovirus serotypes. Liver infection by the FX-Ad5 complex is mediated through a heparin-binding exosite in the FX serine protease domain. This study reveals an unanticipated function for hexon in mediating liver gene transfer in vivo. PMID:18267072

  11. 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 ...

  12. 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.

  13. 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.

  14. Orthotopic liver transplantation

    International Nuclear Information System (INIS)

    Liver transplantation is a life-saving therapeutic option in many patients with end-stage liver disease. Experience with MR imaging of the liver allograft is limited, however. This paper reports twenty-one patients who had undergone liver transplantation studied with MR imaging. A perivascular collar surrounding the portal vein was demonstrated in all 21 patients. In 17 of them, the collar was also observed around peripheral portal branches. The collar had low signal intensity (SI) on T1-weighted and high SI on multiecho images. Perihilar fluid collections that were connected to the perivascular collar were demonstrated in four patients. Laboratory analysis of the aspirated fluid demonstrated liver lymph in three patients. The perivascular collar appears to be related to impaired lymph drainage from surgical interruption of lymphatic vessels. In contrast to recent CT reports, however, a perivascular collar around peripheral portal venous branches does not appear to be a sign specific for rejection, since only two of the 17 patients with a peripheral perivascular collar had rejection at the time of MR imaging. The authors conclude that perivascular collar is a normal finding in hepatic transplants. It should not be mistaken for dilated bile ducts. A perivascular collar around peripheral portal branches does not correlate to rejection

  15. in Human Liver Diseases

    Directory of Open Access Journals (Sweden)

    Minoru Fujimoto

    2010-01-01

    Full Text Available Toll-like receptor (TLR signaling pathways are strictly coordinated by several mechanisms to regulate adequate innate immune responses. Recent lines of evidence indicate that the suppressor of cytokine signaling (SOCS family proteins, originally identified as negative-feedback regulators in cytokine signaling, are involved in the regulation of TLR-mediated immune responses. SOCS1, a member of SOCS family, is strongly induced upon TLR stimulation. Cells lacking SOCS1 are hyperresponsive to TLR stimulation. Thus, SOCS1 is an important regulator for both cytokine and TLR-induced responses. As an immune organ, the liver contains various types of immune cells such as T cells, NK cells, NKT cells, and Kupffer cells and is continuously challenged with gut-derived bacterial and dietary antigens. SOCS1 may be implicated in pathophysiology of the liver. The studies using SOCS1-deficient mice revealed that endogenous SOCS1 is critical for the prevention of liver diseases such as hepatitis, cirrhosis, and cancers. Recent studies on humans suggest that SOCS1 is involved in the development of various liver disorders in humans. Thus, SOCS1 and other SOCS proteins are potential targets for the therapy of human liver diseases.

  16. Exosomes in liver pathology.

    Science.gov (United States)

    Sato, Keisaku; Meng, Fanyin; Glaser, Shannon; Alpini, Gianfranco

    2016-07-01

    Exosomes are small (∼100nm) membrane-bound extracellular vesicles released by various types of cells into biological fluids. They contain proteins, mRNAs and miRNAs as cargo. Different cell types can take up exosomes by endocytosis and the cargo contained within them can be transferred horizontally to these recipient cells. Exosomal proteins and miRNAs can be functional and regulate physiological cell events modifying the microenvironment in target cells, a key event of liver pathology. Exosome-mediated cell-cell communication can alter tumor growth, cell migration, antiviral infection and hepatocyte regeneration, indicating that exosomes have great potential for development as diagnostic or therapeutic tools. Analyses of circulating total or exosomal miRNAs have identified a large number of candidate miRNAs that are regulated in liver diseases, and the diagnostic testing using single or multiple miRNAs shows good sensitivity and specificity. Some candidate miRNAs have been identified to play an important role in various liver disorders. This review summarizes recent findings on the role of extracellular vesicles in liver diseases and their diagnostic and therapeutic potential, mainly focusing on exosomes but also includes microvesicles in liver pathology. PMID:26988731

  17. A case of Long QT syndrome type 3 aggravated by beta-blockers and alleviated by mexiletine: the role of epinephrine provocation test.

    Science.gov (United States)

    Park, Junbeom; Kim, Sook Kyoung; Pak, Hui-Nam

    2013-03-01

    Long QT syndrome (LQTs) is an uncommon genetic disease causing sudden cardiac death with Torsade de Pointes (TdP). The first line drug treatment has been known to be β-blocker. We encountered a 15-year-old female student with LQTs who had prolonged QTc and multiple episodes of syncope or agonal respiration during sleep. Although her T wave morphology in surface electrocardiography resembled LQTs type 1, her clinical presentation was unusual. During the epinephrine test, TdP was aggravated during β-blocker medication, but alleviated by sodium channel blocker (mexiletine). Therefore, she underwent implantable cardioverter defibrillator implantation. PMID:23364992

  18. 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.

  19. 蛇床子素对小鼠实验性肝损伤的干预效应%Interventional effect of osthol on experimental liver injury in mice

    Institute of Scientific and Technical Information of China (English)

    周红林; 刘建新; 周俐; 周青; 杨庆春; 张文平

    2006-01-01

    明显降低四氯化碳肝损伤小鼠肝脏丙二醛含量(P<0.05),蛇床子素50 mg/kg组虽没有显著性抑制四氯化碳所致的丙二醛含量的升高,但有抑制四氯化碳所致肝损伤丙二醛含量的趋势.③四氯化碳肝损伤模型组肝组织明显损伤,肝细胞浊肿、气球样变性,病变以肝小叶中央静脉周围为重.肝小叶内可见轻度、中度肝细胞点状、碎片状坏死;坏死区内有中、重度淋巴细胞和浆细胞浸润,汇管区内有单核细胞浸润.蛇床子素50,100 mg/kg组也有不同程度的肝细胞破坏、炎性细胞浸润等肝损伤病变,但与模型组比较损伤程度明显减轻,尤其是100 mg/kg剂量组表现更为明显.结论:蛇床子素能保护四氯化碳所致小鼠肝损伤,表现为降低血清谷丙转氨酶和谷草转氨酶活力和肝脏丙二醛含量.%BACKGROUND: Osthol is a simple coumarin from Cnidium monnier (L.)Cusson which has been long used of in China as a herbal medicine for arthritis. We have previously observed protective effects of osthol on Ca2+antagonism, oxidative stress and inflammation. And other researches reported that it could inhibit increase of serum xanthine oxidase induced by liver tumor.OBJECTIVE: To investigate the protective effect of osthol on carbon tetrachloride (CCl4)-induced liver injury of mice.DESIGN: Completely randomized controlled study.SETTING: Department of Pharmacology, Gannan Medical College; Physical Education, Gannan Normal College.MATERIALS: A total of 40 Kunming mice were of both genders and weighing (20±2) g. Osthol was provided by Chengdu Longquan High-Tech Natural Pharmaceutical Co. Ltd.METHODS: The experiment was performed at Department of Pharmacology, Gannan Medical College from March to July 2005. Forty mice were randomly divided into control, model, osthol (ip 50 g/kg) and osthol (ip 100 g/kg) groups with 10 in each. Separately once a day for 15 consecutive days, the control and model groups were equalized injected

  20. Ex vivo expansion of circulating CD34(+) cells enhances the regenerative effect on rat liver cirrhosis.

    Science.gov (United States)

    Nakamura, Toru; Koga, Hironori; Iwamoto, Hideki; Tsutsumi, Victor; Imamura, Yasuko; Naitou, Masako; Masuda, Atsutaka; Ikezono, Yu; Abe, Mitsuhiko; Wada, Fumitaka; Sakaue, Takahiko; Ueno, Takato; Ii, Masaaki; Alev, Cantas; Kawamoto, Atsuhiko; Asahara, Takayuki; Torimura, Takuji

    2016-01-01

    Ex vivo expansion of autologous cells is indispensable for cell transplantation therapy of patients with liver cirrhosis. The aim of this study was to investigate the efficacy of human ex vivo-expanded CD34(+) cells for treatment of cirrhotic rat liver. Recipient rats were intraperitoneally injected with CCl4 twice weekly for 3 weeks before administration of CD34(+) cells. CCl4 was then re-administered twice weekly for 3 more weeks, and the rats were sacrificed. Saline, nonexpanded or expanded CD34(+) cells were injected via the spleen. After 7 days, CD34(+) cells were effectively expanded in a serum-free culture medium. Expanded CD34(+) cells were also increasingly positive for cell surface markers of VE-cadherin, VEGF receptor-2, and Tie-2. The expression of proangiogenic growth factors and adhesion molecules in expanded CD34(+) cells increased compared with nonexpanded CD34(+) cells. Expanded CD34(+) cell transplantation reduced liver fibrosis, with a decrease of αSMA(+) cells. Assessments of hepatocyte and sinusoidal endothelial cell proliferative activity indicated the superior potency of expanded CD34(+) cells over non-expanded CD34(+) cells. The inhibition of integrin αvβ3 and αvβ5 disturbed the engraftment of transplanted CD34(+) cells and aggravated liver fibrosis. These findings suggest that expanded CD34(+) cells enhanced the preventive efficacy of cell transplantation in a cirrhotic model. PMID:27162932

  1. 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.

  2. MANAGEMENT OF LIVER TRAUMA

    Directory of Open Access Journals (Sweden)

    Dova Subba

    2016-03-01

    Full Text Available AIM To estimate the incidence of Liver Trauma injuries and grade their severity of injury. To assess the factors responsible for morbidity and mortality after Liver Trauma. To study the postoperative complications and the management of Liver Trauma. MATERIALS AND METHODS The present prospective study was conducted on 100 patients who were admitted to Department of General Surgery for treatment who were managed operatively or non-operatively for abdominal trauma and having liver injury forms the material of the study. This study was conducted over a span of 24 months from June 2013 to November 2015. RESULTS Maximum number of patients are in the age group of 21-30 years (46%. 85% patients (85/100 are males and 15% of patients (15/100 are females. Lapse time of injury and admission varied from 25 minutes to 66 hours and 30 minutes. 75 % of the patients (75/100 presented within 24 hours after injury. Death rate of patients who reached hospital after 24 hours of injury was higher than the patients who reached hospital within 24 hours of injury. 28% of patients (28/100 had associated bony injuries, out of which 5% of patients (5/100 expired due to primary haemorrhage of fractured femur. More than one segment was injured in many patients. Segment V is involved commonly making 55% (55/100 of patients. Next common segment involved is segment VII, making 39% (39/100. CONCLUSION Mechanism of injury is the important factor which is responsible for morbidity in liver injury. Nonoperative management proved to be safe and effective and often has been used to treat patients with liver trauma.

  3. 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.

  4. 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. PMID:27082951

  5. 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

  6. Atlas of liver imaging

    International Nuclear Information System (INIS)

    This atlas is an outcome of an IAEA co-ordinated research programme. In addition to Japan, nine other Asian countries participated in the project and 293 liver scintigrams (116 from Japanese institutions and 177 from seven Asian countries) were evaluated by physicians from the participating Asian countries. The computer analysis of the scan findings of the individual physicians was carried out and individual scores have been separately tabulated for: (a) scan abnormality; (b) space occupying lesions; (c) cirrhosis and (d) diffuse liver diseases like hepatitis. Refs, figs and tabs

  7. Colorectal liver metastases.

    OpenAIRE

    Burke, D; Allen-Mersh, T G

    1996-01-01

    Each year in the UK, between 12-14,000 people develop liver metastases from colorectal cancer. These metastases will contribute to the death of the patient in about 80% of cases. Treatments aimed at these tumours are best administered when the tumour is small. Current investigative methods allow tumours as small as 0.5 mm to be detected, and should be offered to all colorectal cancer patients at risk of developing liver metastases. Surgery remains the only curative treatment for these tumours...

  8. 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.

  9. 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....

  10. Radiofrequency Ablation of Liver Tumors

    Science.gov (United States)

    ... hepatocellular carcinoma , which is a primary liver cancer (meaning it begins in the liver). colon cancer that ... to local anesthetic medications, general anesthesia or to contrast materials containing iodine (sometimes referred to as "dye" ...

  11. LIVER AND BILIARY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    11.1 Liver function2004244 Comparison of the biological Features be-tweenhuman fetal hepatocyte and immortalized L-02 hepatocyte in vitro. KONG Weiwei (孔炜炜), et al. Dept Radiolt Zhongda Hosp, Southeast Univ, Nanjing 210009. Chin J Radiol 2004;38(2):119-123. Objective: To evaluate the feasibilities of the po-

  12. 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.

  13. 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...

  14. Radioembolization of liver tumors

    NARCIS (Netherlands)

    Hoven, A.F. van den

    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

  15. 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....

  16. Biliary complications following liver transplantation

    OpenAIRE

    Kochhar, Gursimran; Parungao, Jose Mari; Hanouneh, Ibrahim A; Parsi, Mansour A

    2013-01-01

    Biliary tract complications are the most common complications after liver transplantation. These complications are encountered more commonly as a result of increased number of liver transplantations and the prolonged survival of transplant patients. Biliary complications remain a major source of morbidity in liver transplant patients, with an incidence of 5%-32%. Post liver transplantation biliary complications include strictures (anastomotic and non-anastomotic), leaks, stones, sphincter of ...

  17. Medical Aspects of Liver Transplantation

    OpenAIRE

    Van Thiel, David H.; Schade, Robert R.; GAVALER, JUDITH S.; Shaw, Byers W.; Iwatsuki, Shunzaburo; Starzl, Thomas E.

    1984-01-01

    The methods used to screen prospective candidates for orthotopic liver transplantation are described. Both the indication and the contraindications for the procedure are discussed. The timing of the procedure during the course of an individual candidate’s liver disease is also discussed. Additionally, the institutional requirements of a liver transplant center are identified. Finally, the problems experienced by a liver transplant patient and his physician during the postoperative period are ...

  18. [Dietotherapy children with liver diseases].

    Science.gov (United States)

    Pavlovskaia, E V; Strokova, T V; Topil'skaia, N V; Isakova, V A

    2009-01-01

    In children with liver diseases disorders of the nutritional status appear more quickly and delay normal growth and development. Administration of the nutritional support based on nosological and syndromal approaches lets provide optimal conditions for normalization of the liver functions, improves efficiency of therapy and prognosis of the disease. The article contents modern recommendations on the organization of nutrition in children with different liver diseases, correction of metabolic disorders during complications of liver pathology. PMID:20120964

  19. Serum parameters of liver fibrosis

    OpenAIRE

    Zanten, R. A A

    1991-01-01

    textabstractChronic liver disease is often associated with deposition of fibrous tissue, a process which together with the destruction of normal liver and liver cell regeneration, leads to the condition called cirrhosis. Cirrhosis is known to be associated with a reduction in life expectancy. In recent years there has been an increasing interest in the pathogenesis of cirrhosis and in the possibilities reversing the process of fibrogenesis. Liver biopsy is the present "gold standard" for dete...

  20. 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.