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Sample records for aggravates experimental liver

  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. Arterial hypertension aggravates innate immune responses after experimental stroke

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    Karoline Möller

    2015-11-01

    Full Text Available Arterial hypertension is not only the leading risk factor for stroke, but also attribute to impaired recovery and poor outcome. The latter could be explained by hypertensive vascular remodeling that aggravates perfusion deficits and blood brain barrier disruption. However, besides vascular changes, one could hypothesize that activation of the immune system due to pre-existing hypertension may negatively influence post-stroke inflammation and thus stroke outcome. To test this hypothesis, male adult spontaneously hypertensive rats (SHR and normotensive Wistar Kyoto rats (WKY were subjected to photothrombotic stroke. One and three days after stroke, infarct volume and functional deficits were evaluated by magnetic resonance imaging and behavioral tests. Expression levels of adhesion molecules and chemokines, along with the post-stroke inflammatory response was analyzed by flow cytometry, quantitative real-time PCR and immunohistochemistry in rat brains four days after stroke. Although comparable at day one, lesion volumes were significantly larger in SHR at day three. The infarct volume showed a strong correlation with the amount of CD45 highly positive leukocytes present in the ischemic hemispheres. Functional deficits were comparable between SHR and WKY. Brain endothelial expression of intercellular adhesion molecule 1 (ICAM-1, vascular cell adhesion molecule 1 (VCAM-1 and P-selectin (CD62P was neither increased by hypertension nor by stroke. However, in SHR, brain infiltrating myeloid leukocytes showed significantly higher surface expression of ICAM-1 which may augment leukocyte transmigration by leukocyte-leukocyte interactions. The expression of chemokines that primarily attract monocytes and granulocytes was significantly increased by stroke and, furthermore, by hypertension. Accordingly, ischemic hemispheres of SHR contain considerably higher numbers of monocytes, macrophages and granulocytes. Exacerbated brain inflammation in SHR may

  3. 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...

  4. 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...

  5. 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

  6. Dual role of chloroquine in liver ischemia reperfusion injury: reduction of liver damage in early phase, but aggravation in late phase.

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    Fang, H; Liu, A; Dahmen, U; Dirsch, O

    2013-01-01

    The anti-malaria drug chloroquine is well known as autophagy inhibitor. Chloroquine has also been used as anti-inflammatory drugs to treat inflammatory diseases. We hypothesized that chloroquine could have a dual effect in liver ischemia/reperfusion (I/R) injury: chloroquine on the one hand could protect the liver against I/R injury via inhibition of inflammatory response, but on the other hand could aggravate liver I/R injury through inhibition of autophagy. Rats (n=6 per group) were pre-treated with chloroquine (60 mg/kg, i.p.) 1 h before warm ischemia, and they were continuously subjected to a daily chloroquine injection for up to 2 days. Rats were killed 0.5, 6, 24 and 48 h after reperfusion. At the early phase (i.e., 0-6 h after reperfusion), chloroquine treatment ameliorated liver I/R injury, as indicated by lower serum aminotransferase levels, lower hepatic inflammatory cytokines and fewer histopathologic changes. In contrast, chloroquine worsened liver injury at the late phase of reperfusion (i.e., 24-48 h after reperfusion). The mechanism of protective action of chloroquine appeared to involve its ability to modulate mitogen-activated protein kinase activation, reduce high-mobility group box 1 release and inflammatory cytokines production, whereas chloroquine worsened liver injury via inhibition of autophagy and induction of hepatic apoptosis at the late phase. In conclusion, chloroquine prevents ischemic liver damage at the early phase, but aggravates liver damage at the late phase in liver I/R injury. This dual role of chloroquine should be considered when using chloroquine as an inhibitor of inflammation or autophagy in I/R injury. PMID:23807223

  7. 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.

  8. 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

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

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    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...

  10. 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.

  11. Case of cytomegalovirus retinitis aggravated by sub-Tenon injection of triamcinolone acetonide with subsequent metastatic liver cancer

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    Yamamoto Y

    2013-03-01

    Full Text Available Yumiko Yamamoto,1 Yoshitake Kato,2 Hitoshi Tabuchi,2 Atsuki Fukushima11Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi, Japan; 2Department of Ophthalmology, Tsukazaki Hospital, Hyogo, JapanAbstract: We report a case of cytomegalovirus (CMV retinitis in an immunocompetent patient who was resistant to antiviral treatment, and in whom fatal metastatic liver cancer was later detected. A 74-year-old Japanese man visited our ophthalmology clinic in May 2011. He had a history of well controlled type 2 diabetes and colon cancer, and underwent successful surgical treatment in 2008. In April 2011, he was diagnosed with uveitis affecting his left eye and received posterior sub-Tenon injection of triamcinolone acetonide. He was referred to us because of aggravation of the retinal lesion. Funduscopic examination of the left eye revealed arcuate, whitish, necrotizing retinitis with hemorrhage along the temporal arcade of the retina. Polymerase chain reaction of the aqueous fluid was positive for CMV DNA. Because of diagnosis of CMV retinitis in his left eye, he was referred to an internist and investigated for systemic CMV infection or any serious disease which could cause immunocompromise, but neither was detected. Despite an intensive course of intravitreous ganciclovir and oral valganciclovir, the retinitis did not resolve. In June 2012, 14 months after the initial ocular symptoms, metastatic liver cancer was found and the patient passed away. When CMV retinitis is resistant to antiviral treatment or recurs in an immunocompetent patient, it is important that ophthalmologists undertake systemic investigation for occult malignancy.Keywords: cytomegalovirus, retinitis, uveitis, immunocompromised, immunocompetent, triamcinolone acetonide, diabetes, ganciclovir, valganciclovir

  12. 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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  14. Acute exposure to air pollution particulate matter aggravates experimental myocardial infarction in mice by potentiating cytokine secretion from lung macrophages.

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    Marchini, Timoteo; Wolf, Dennis; Michel, Nathaly Anto; Mauler, Maximilian; Dufner, Bianca; Hoppe, Natalie; Beckert, Jessica; Jäckel, Markus; Magnani, Natalia; Duerschmied, Daniel; Tasat, Deborah; Alvarez, Silvia; Reinöhl, Jochen; von Zur Muhlen, Constantin; Idzko, Marco; Bode, Christoph; Hilgendorf, Ingo; Evelson, Pablo; Zirlik, Andreas

    2016-07-01

    Clinical, but not experimental evidence has suggested that air pollution particulate matter (PM) aggravates myocardial infarction (MI). Here, we aimed to describe mechanisms and consequences of PM exposure in an experimental model of MI. C57BL/6J mice were challenged with a PM surrogate (Residual Oil Fly Ash, ROFA) by intranasal installation before MI was induced by permanent ligation of the left anterior descending coronary artery. Histological analysis of the myocardium 7 days after MI demonstrated an increase in infarct area and enhanced inflammatory cell recruitment in ROFA-exposed mice. Mechanistically, ROFA exposure increased the levels of the circulating pro-inflammatory cytokines TNF-α, IL-6, and MCP-1, activated myeloid and endothelial cells, and enhanced leukocyte recruitment to the peritoneal cavity and the vascular endothelium. Notably, these effects on endothelial cells and circulating leukocytes could be reversed by neutralizing anti-TNF-α treatment. We identified alveolar macrophages as the primary source of elevated cytokine production after PM exposure. Accordingly, in vivo depletion of alveolar macrophages by intranasal clodronate attenuated inflammation and cell recruitment to infarcted tissue of ROFA-exposed mice. Taken together, our data demonstrate that exposure to environmental PM induces the release of inflammatory cytokines from alveolar macrophages which directly worsens the course of MI in mice. These findings uncover a novel link between air pollution PM exposure and inflammatory pathways, highlighting the importance of environmental factors in cardiovascular disease. PMID:27240856

  15. Selective depletion of Foxp3+ Treg during sensitization phase aggravates experimental allergic airway inflammation.

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    Baru, Abdul Mannan; Hartl, Andrea; Lahl, Katharina; Krishnaswamy, Jayendra Kumar; Fehrenbach, Heinz; Yildirim, Ali O; Garn, Holger; Renz, Harald; Behrens, Georg M N; Sparwasser, Tim

    2010-08-01

    Recent studies highlight the role of Treg in preventing unnecessary responses to allergens and maintaining functional immune tolerance in the lung. We investigated the role of Treg during the sensitization phase in a murine model of experimental allergic airway inflammation by selectively depleting the Treg population in vivo. DEpletion of REGulatory T cells (DEREG) mice were depleted of Treg by diphtheria toxin injection. Allergic airway inflammation was induced using OVA as a model allergen. Pathology was assessed by scoring for differential cellular infiltration in bronchoalveolar lavage, IgE and IgG1 levels in serum, cytokine secretion analysis of lymphocytes from lung draining lymph nodes and lung histology. Use of DEREG mice allowed us for the first time to track and specifically deplete both CD25(+) and CD25(-) Foxp3(+) Treg, and to analyze their significance in limiting pathology in allergic airway inflammation. We observed that depletion of Treg during the priming phase of an active immune response led to a dramatic exacerbation of allergic airway inflammation in mice, suggesting an essential role played by Treg in regulating immune responses against allergens as early as the sensitization phase via maintenance of functional tolerance. PMID:20544727

  16. 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.

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

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    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 ...

  18. 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

  19. 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...

  20. Ideal Experimental Rat Models for Liver Diseases.

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    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

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

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    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

  2. Oxidative Stress and Pulmonary Changes in Experimental Liver Cirrhosis

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    Renata Salatti Ferrari

    2012-01-01

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

  3. Effects of melatonin on liver of rats with experimental hyperthyroid

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    Oner J.

    2005-01-01

    Full Text Available The aim of this study was to investigate the structural changes that occurred in the liver of rats with experimental hyperthyroidism and the possible effects of melatonin on these changes. The animals were designated as control group (group I, 3,3', 5-Triiodo-I-Thyronine (T3 injected group (group II and T3+ melatonin injected group (group III. At the end of study, tissue specimens were examined for changes in structure. In the T3 injected group dilatation in sinusoids and pale cytoplasm were observed, as well as an increased number of the Kupffer cells and an increased amount of glycogen. In T3 + melatonin injected group, the amount of glycogen was similar to the T3 injected groups while the number of Kupffer cells increased but sinusoid largeness and hepatocyte structure were similar to the control. On electron microscopic examination the mitochondria of T3 injected group were slightly larger than those of the control group. In T3 + melatonin injected group enlargement in the spaces of Disse, increased number of lipid vacuoles of Ito cells and increased number of microvilli of hepatocytes were observed. Kupffer cells were more active in this group. The results of this study indicate that T3 injection causes structural changes in the liver, and melatonin hormone has a small, if any, protective effect on the liver of rats with hyperthyroid.

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. Experimental modified orthotopic piggy-back liver autotransplantation

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-07-15

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

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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...

  14. New semi-spherical radiofrequency energy device for liver resection: an experimental study in pigs

    OpenAIRE

    Vávra, Petr; Škrobánková, Martina; Grepl, Jan; Crha, Michal; Penhaker, Marek; Jurčíková, Jana; Škorič, Miša; Raušer, Petr; Ostruszka, Petr; Ihnát, Peter; Delongová, Patricie; Dvořáčková, Jana; Procházka, Václav; Šalounová, Dana; Habib, Nagy

    2015-01-01

    The aim of this experimental study was to verify a new semi-spherical surgical tool for bipolar radiofrequency liver ablation, which can solve some of the disadvantages of the commonly used device, such as long duration of ablation. A total of 12 pigs which were randomly divided into two groups were used. Each pig underwent resection of the two liver lobes. In group 1, pigs were treated with the commonly used device; in group 2 the newly developed semispherical device was used....

  15. Aggravating Impact of Nanoparticles on Immune-Mediated Pulmonary Inflammation

    OpenAIRE

    Ken-Ichiro Inoue; Hirohisa Takano

    2011-01-01

    Although the adverse health effects of nanoparticles have been proposed and are being clarified, their aggravating effects on pre-existing pathological conditions have not been fully investigated. In this review, we provide insights into the immunotoxicity of both airborne and engineered nanoparticles as an exacerbating factor on hypersusceptible subjects, especially those with immune-mediated pulmonary inflammation, using our in vivo experimental model. First, we exhibit the effects of nanop...

  16. 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. ...

  17. Oxidative stress associated with pathological lesions in the liver of rats experimentally infected by Fasciola hepatica.

    Science.gov (United States)

    Bottari, Nathieli B; Mendes, Ricardo E; Lucca, Neuber J; Schwertz, Claiton I; Henker, Luan C; Olsson, Débora C; Piva, Manoela M; Sangoi, Manuela; Campos, Luízi P; Moresco, Rafael N; Jaques, Jeandre A; Da silva, Aleksandro S

    2015-12-01

    The aim of this study was to analyze the antioxidant status and oxidative profile in serum and liver of rats experimentally infected with Fasciola hepatica and its relationship with pathological findings. Twenty-four rats were divided into two groups: group A consisted of 12 healthy rats and group B of 12 rats infected orally with 20 metacercaria of F. hepatica. At days 20 and 150 post-infection (PI), blood and liver samples of six animals from each group were collected. The protein oxidation (AOPP technique: advanced oxidation protein products) and antioxidants (FRAP technique: ferric reducing antioxidant power) levels were measured in serum and liver. Furthermore, nitrite/nitrate (NOx) levels and lipid peroxidation (TBARS technique: thiobarbituric acid reactive substances) were measured in liver. AOPP and FRAP levels were increased (P < 0.05) in serum and liver of infected animals in acute and chronic infection when compared with healthy animals. The same occurred with TBARS and NOx levels in the liver (P < 0.05). Histopathology revealed periportal fibrous hepatitis, composed of an abundant inflammatory infiltrate in portal spaces on infected animals, as well as bile duct hyperplasia. The results found seem to be related to the host free radical production demonstrated in serum samples and liver due to the parasite infection. PMID:26311170

  18. 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

  19. Applications of 1H-NMR relaxometry in experimental liver studies

    International Nuclear Information System (INIS)

    Purpose of this study was to investigate applications of proton nuclear magnetic resonance (1H-NMR) relaxometry in experimental medicine. Relaxometry was performed by measurements of spin-lattice (T1) and spin-spin (T2) relaxation time parameters on liver biopsies up to four hours after biopsy excision. Variations of relaxation times due to species and strain, different sample handling and different liver damage models, ethionine fatty liver and paracetamol liver necrosis, were investigated. Cell integrity effects were studied on homogenized liver samples. Relaxation time parameters, especially 'main' components T1A and T2A of biexponential model fit, were identified to react very sensitive after tissue damages as well as to cell viability. Thus, investigation of stored liver grafts was performed in order to evaluate the possibility of a rapid liver graft viability testing method for human liver transplantation surgery by 1H-NMR relaxometry. Another series of measurements was performed to investigate the applicability of isoflurane anesthesia for in vivo NMR experiments. This study proved the good appropriateness of isoflurane for that purpose provided that physiological monitoring and individual adjustment of anesthesia are performed. In these investigations it could be revealed that mainly T1A and T2A are influenced by tissue condition and that different information is inherent in these two parameters, with T2A reflecting tissue viability and changes of tissue conditions very sensitively but rather unspecifically in respect to the damage applied. Based on these results the following future applications of 1H-NMR relaxometry are suggested : (1) model investigations, (2) investigation of given pathologies, (3) investigation of basic requirements for in vivo NMR and (4) application in a liver graft viability testing protocol, which seems to be the most important future application of 1H-NMR relaxometry in medicine. (author)

  20. Experimental study on quantitative analysis of fatty liver by computed tomography in rabbit

    International Nuclear Information System (INIS)

    For the study of correlation of CT number and fatty contact of the liver, total 35 rabbit were used. The rabbits were divided into one control and three experimental groups according to the amount of carbon tetrachloride, administered 1 ml, 2 ml, and 3 ml per kg of body weight respectively. The carbon tetrachloride was administered via intragastric route. CT was performed 72 hours following administration of carbon tetrachloride, and immediately prior to CT scan each rabbit was anesthetized by means of IM injection of ketamine and IV injection of succinylcholine to stop motion and respiration. CT numbers were measured and histological study for the deposition of fat in the liver tissue was done. Also biochemical analysis of lipid in the blood and in the extraction of liver tissue was performed. Comparison of CT number with biochemical and histological data was done. The result was as follows: 1. In each experimental group, the degree of accumulation of fat in the liver was proportional to the amount of carbon tetrachloride. 2. Degree of decreasing CT number was correlated with the increase in the accumulation of fat in the liver. 3. In the control and experimental (1, 2, 3) groups, when the amount of carbon tetrachloride increased, the amount of total lipid, cholesterol and triglyceride on biochemical analysis of the liver increased. Also increase in the amount of plasma lipids on biochemical analysis and great degree of increase in accumulation of fat in the liver on histological examination were seen. But no changes in the amount of phospholipid and protein on biochemical analysis of the liver were noticed. 4. Increase in the amount of total lipid could make a change in the CT number of the liver remarkably (r=-0.63). As the amount of cholesterol and triglyceride increased, the CT number of the liver decreased (r=-0.61 and r=-0.76 respectively). But there was no significant correlation between the amount of protein and phospholipid and the degree of decrease in

  1. [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

  2. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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

  5. 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...

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

    Directory of Open Access Journals (Sweden)

    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

  7. The Effect of Montelukast on Liver Damage in an Experimental Obstructive Jaundice Model

    OpenAIRE

    Kuru, Serdar; Kismet, Kemal; Barlas, Aziz M.; Tuncal, Salih; Celepli, Pinar; Surer, Hatice; Ogus, Elmas; Ertas, Ertugrul

    2015-01-01

    Background Montelukast is a cysteinyl-leukotriene type 1 (CysLT1) selective receptor antagonist. In recent years, investigations have shown that montelukast possesses secondary anti-inflammatory activities and also antioxidant effects. For this reason, we aimed to determine the possible effects of montelukast on liver damage in experimental obstructive jaundice. Methods 30 Wistar-Albino male rats were randomized and divided into three groups of 10 animals each: group I, sham-operated; group I...

  8. 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 ...

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. Portal traid changes in liver associated rapeseed oil diet supplemented with atherogenic element: an experimental study

    International Nuclear Information System (INIS)

    This experimental study was designed to see the possible effects of rapeseed oil on liver morphology. For this purpose, 60 albino rats of eight weeks age were selected and divided into five groups of twelve animals each with equal number of males and females. Group I, normal control, was fed on synthetic diet, Group II was on low rapeseed oil diet only and group III was on low rapeseed + hypercholesterolemic diet. Group IV was on high rapeseed oil diet only and Group V was on high rapeseed oil + hypercholesterolemic diet for the next 24 weeks. Histological examination was done on H and E, reticulin, trichrome and oil red O stains. Liver revealed mild to severe type of Portal triad fibrosis in groups II, III, IV and V. These findings were statistically significant when compared with control Group I. While bile duct proliferation (BDP) was mild in Group II and IV. Hence it is concluded that Rapeseed oil proved to be beneficial diet. It causes mild hepatic injury in low and high concentration. Hypercholesterolemic diet causes moderate to severe morphological changes in liver. (author)

  16. 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

  17. 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

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

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    Davide Povero

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

  19. Experimental study on ablating goat liver tissue with ultrasound imaging guided percutaneous irreversible electroporation

    Directory of Open Access Journals (Sweden)

    Ying LIU

    2011-03-01

    Full Text Available Objective To investigate the proper method of percutaneous irreversible electroporation(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(100 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 provides a fundamental experimental work for future studies on clinical application of IRE.

  20. Application of interleukin-22 mediates protection in experimental acetaminophen-induced acute liver injury.

    Science.gov (United States)

    Scheiermann, Patrick; Bachmann, Malte; Goren, Itamar; Zwissler, Bernhard; Pfeilschifter, Josef; Mühl, Heiko

    2013-04-01

    Acetaminophen (APAP, paracetamol)-induced hepatotoxicity, although treatable by timely application of N-acetylcysteine, can be fatal. Because it is among the common causes of acute liver failure in intensive care units and in light of its gradually increasing incidence, the need for novel therapeutic strategies aimed at severe intoxication is apparent. Recently, it has been shown that IL-22, a STAT3-activating cytokine, has the capability to mediate liver protection. Herein, the protective potential of IL-22 in murine APAP-induced hepatotoxicity was assessed. Intravenous administration of prophylactic IL-22 significantly reduced serum alanine aminotransferase levels and histopathologic damage in APAP-induced liver injury, a process that coincided with increased hepatocyte proliferation in vivo. Concomitant gene expression analysis revealed hepatic induction of genes prototypically up-regulated by the IL-22/STAT3 axis, among others suppressor of cytokine signaling-3, lipocalin-2, and α1-antichymotrypsin. Notably, in a translational setting of therapeutic treatment 2 hours after APAP, IL-22 supported protection in the context of suboptimal N-acetylcysteine dosing. IL-22 likewise connected to augmented hepatocyte proliferation in this experimental setting. As detected by analysis of inflammatory cytokine production, systemically applied IL-22 did not display acute immunomodulation/stimulation in otherwise untreated or endotoxemic mice. Those latter observations clearly confirm acute tolerability of systemically applied IL-22. Observations presented altogether suggest that therapeutic IL-22 administration is a conceivable tissue-protective regimen aimed at hard-to-treat patients with severe APAP-induced hepatotoxicity. PMID:23375450

  1. 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.

  2. 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

  3. Liver fibrosis in guinea pigs experimentally induced by combined copper and aflatoxin application.

    Science.gov (United States)

    Schiller, F; Lippold, U; Heinze, R; Hoffmann, A; Seffner, W

    1998-09-01

    Aflatoxin B1 alone (0.05 mg resp. 0.037 mg/kg/d), copper alone (6.6 mg/kg/d or 200 mg/l drinking water) or a combination of both was administrated orally for 6 months to young guinea pigs from the first/second day of life. In the copper group there were no pathomorphological changes. For the aflatoxin B1 group liver damage was established. In the combined group liver injury was more frequent and more severe compared to the aflatoxin B1 group. Compared with the copper group biliary copper excretion was diminished and the kidney copper content was elevated in the Afl. B1 + Cu group. While copper concentrations in bile and kidney correlated with other parameters, notably the pathological lesions of the liver, no such correlation was found for liver copper. Therefore in this experiment the degree of Cu accumulation was not decisive for the liver lesions. The livers' capacity for excreting Cu by bile seems to be a much more important factor. Histologically only the livers of the combined group exhibited degeneration, atrophy and steatosis of liver cells, and a fibrosis more or less pronounced. For childhood cirrhosis (ICC and ICT), a combined etiology--a liver damaging agent plus elevated alimentary copper--is a plausible hypothesis. PMID:9784033

  4. 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

  5. Contribution of dermal-derived mesenchymal cells during liver repair in two different experimental models

    Science.gov (United States)

    Tan, Li; Dai, Tingyu; Liu, Dengqun; Chen, Zelin; Wu, Liao; Gao, Li; Wang, Yu; Shi, Chunmeng

    2016-01-01

    Progressive liver disease is a major health issue for which no effective treatment is available, leading to cirrhosis and orthotopic liver transplantation. However, the lack of availability of donor organs and other adverse factors including rejection limit its extensive clinical application. Cell-based therapy using mesenchymal stem/stromal cells (MSCs) may represent an attractive therapeutic option. Dermal-derived mesenchymal cells (DMCs) are attractive as one of the abundant sources from which to isolate mesenchymal cells for therapeutic applications and can be easily accessed with minimal harm to the donor. In this study, we used two different animal models to investigate potential therapeutic effect of DMCs transplantation in liver injury. We found that DMCs administration alleviated liver fibrosis and restored the liver function in fibrotic mice induced by CCl4. Furthermore, in an acute irradiation induced damage model, a unique population of DMCs could engraft into the liver tissue for a long period, exhibiting the phenotype of both mesenchymal cells and macrophage cells, and improve the survival of mice exposed to 8 Gy lethally total-body irradiation. These discoveries provide important evidence that DMCs therapy has a beneficial effect on liver injury, and provide new insight into liver injury therapy depending on the alternative cells. PMID:27126764

  6. 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.

  7. 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 ...

  8. Experimental Study of Percutaneous Ethanol Injection in the Rabbit Liver : Correlations Between Sonography and Pathology

    International Nuclear Information System (INIS)

    To investigate the sonographic change and histopathologic correlation after percutaneous ethanol injection(PEI) of normal rabbit liver. Seven rabbits with normal livers were injected ethanol percutaneously under the guidance of ultrasound. Ethanol was injected to five rabbit livers at two different sites with one week interval in two week time period. The echogenecity of the lesion was compared with that of the adjacent normal liver parenchyma and classified into hypo-, iso-, and hyper echoic pattern. The resected specimens were analyzed according to the presence of coagulation necrosis, liquefactive necrosis, and granulation tissue. Sonography after PEI showed hyper echoic focus in all initial injection site which became isoechoic to the surrounding liver parenchyma with time, except for one case. However, one of the lesions became hypoechoic in a week. The isoechoic lesions on sonography were coagulation necrosis and granulation tissue on pathologic correlation. There was also more severe, periportal fibrosis within parenchyma adjacent isoechoic lesion, which became abundant with respect to time. The hypoechoic lesion was correlated with liquefactive necrosis. Histopathologic findings of normal rabbit livers after PEI are coagulation necrosis and granulation tissue. Although the histopathologic changes become progressive with time, the sonographic findings remain isoechoic to the surrounding liver parenchyma. Hypoechogenecity due to liquefactive necrosis may be helpful to differentiate the lesion from normal hepatic parenchyma

  9. 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.

  10. Avidin chase can reduce myelotoxicity associated with radioimmunotherapy of experimental liver micrometastases in mice

    International Nuclear Information System (INIS)

    Myelotoxicity is the main factor which decides the maximum tolerated dose (MTD) in radioimmunotherapy (RIT). Since bone marrow is mostly irradiated from blood radioactivity, enhancing the clearance of unbound circulating radiolabeled antibody is important to reduce myelotoxicity and to increase the MTD. We applied the avidin chase method, which was devised to obtain high tumor-to-background ratios in tumor-targeting, to RIT of experimental liver micrometastases and evaluated its influence on the side effects and therapeutic outcome. Seven days after intrasplenic injection of human colon cancer LS174T cells, nude mice were intravenously injected with biotinylated 131I-labeled anti-CEA monoclonal antibody (MAb) (24-38 μg, 11.1 MBq). Mice of the chase group then received an intravenous injection of avidin twice (24 and 30 h, 72-115 μg each). Biodistribution, side effects (white blood cell counts and body weight change), and short- and long-term therapeutic effects were determined. Avidin chase markedly accelerated the clearance of radiolabeled MAb from the blood (P<0.0001) and normal tissues, resulting in milder leukocytopenia and body weight loss, both of which recovered earlier than in the non-chase group (P<0.01). The tumor uptake of radiolabeled MAb was also decreased by avidin chase, but the metastases-to-background ratios were increased. Avidin chase gave the therapeutic gain ratio of 1.89. Treated groups with and without avidin chase showed significant therapeutic effects compared to the non-treated group. There was no significant difference in the therapeutic effects between the two treated groups. Avidin chase effectively reduced the side effects of RIT and should increase the MTD. (author)

  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. 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)

  13. Protective Role of Pomegranate on Fatty Liver in Obesity: An Experimental

    Directory of Open Access Journals (Sweden)

    Ahmed Hassan El-Rashedy1- Saeed Kamel Belal2- Hossam El-Din Osman3- Gaber

    2011-04-01

    Full Text Available Aim of the work: Fatty liver is the most common cause of abnormal liver function tests. Since obesity and fatty liver can result in serious drawbacks and represent a considerable incidence rate in Saudi Arabia. This country is a famous one of pomegranate. This study aimed at investigating the ameliorating effects of pomegranate on hepatic lipid accumulation in rats with severe fatty liver in order to provide a cheap natural protective medicine since this health problem can affect the entire world economy. Material and methods: Twenty-four male Zucker rats aged 13­15 weeks were used. Animals were allowed free access to food and water for 1 week before starting the experiment. According to the body weight (BW, plasma triglycerides (TG and total cholesterol (TC levels were measured before treatment. The animals were divided into lean control, lean pomegranate (PGF-treated, fatty control and fatty PGF- treated groups (six animals per group. Finally, the animals were weighed after a prompt dislocation of their neck vertebra. Then, the liver was rapidly excised, washed with saline on ice and weighed. In addition, one part of it was cut into slices for studies of lipid determination analysis. The right tibia length (TL was measured for calculation of the ratio of liver weight to TL. A portion of the liver was homogenized and the lipids were extracted with isopropanol. Triglycerides and TC contents in the supernatant were determined. Results: Fatty rats (ZF had shorten TL but their BWs were increased compared to lean rats. Also, ZF rats showed hepatomegaly reflected by increased liver weight and increased ratio of liver weight to TL. Treatment with PGF extract did not change BW and TL, but it reduced liver weight and the ratio in ZF rats. PGF did not affect these parameters in lean ( ZL rats. Fatty rats exhibited severe hepatic steatosis, reflected by a marked increase in hepatic TG as well as hepatic TC contents and fatty droplets visualized by either

  14. Ultrastructural study of the endothelial cells in teleost liver sinusoids under normal and experimental conditions.

    Science.gov (United States)

    Ferri, S; Sesso, A

    1981-01-01

    The ultrastructure of the endothelial cells of liver sinusoids was studied in the teleost, Pimelodus maculatus. These cells have the ability to form pinocytotic vacuoles, starting with the formation of marginal folds. The latter occur in many cells after stimulation by India ink injections and ink particles are ingested by pinocytosis and by micropinocytosis. Desmosomes, structures rarely described between liver sinusoidal endothelial cells, are present in this species. PMID:7273119

  15. 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

  16. 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

  17. Experimental study of electrochemotherapy on implanted liver tumor cells apoptosis of rats

    International Nuclear Information System (INIS)

    Objective: To compare the effects of electrochemotherapy (EChT) on implanted liver tumor cells apoptosis of rats. Methods: Immediate cancerous ascites injection method was used for the formation of rats liver tumor model and then followed by rats liver tumor treatment with EChT. Tumor size, necrosis and apoptosis indexes were observed after one week by imaging or pathologic method. The results were compared with those of control group. Results: Before EChT, rats liver tumor volume appeared as (100 ± 6) mm3 and turned to be (125 ± 10) mm3 one week after EChT, which were significantly smaller than those of the control group [(190 ± 11) mm3], P<0.05. Apoptosis indexes were 9.625 ± 1.172 and 3.523 ± 0.894 in EChT group and control group respectively (P<0.01). Tumor necrosis in EChT group increased significantly than those of the control group. Conclusions: The growth of rats liver tumor is obviously inhibited through inducing apoptosis and promoting necrosis by EChT

  18. 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.

  19. 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

  20. 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...

  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 experimental study of radiation injury on bile duct and liver tissue

    International Nuclear Information System (INIS)

    Objective: To investigate the safety, acceptance and the effective extent of 192Ir-internal irradiation, providing theoretical guidelines for HC. Methods: Sixteen male healthy hybrid dogs enrolled in the experiment were divided into 4 groups of 4 each. The brachytherapy applicator was introduced from gall bladder into the convergence of cystic duct with common hepatic duct during the operation and a small chip of 1 cm3 liver tissue was cut off and taken for control later on. The animals in group A-D were irradiated by 192Ir-internal irradiation with 30 Gy, 40 Gy, 50 Gy arid 60 Gy at the correlative dose points respectively. Animals were put to death after 10 days subsequently, with sampling specimens obtained from radiation cystic duct and the in between liver tissue with the distant cystic duct. The radiation injury of the cystic duct and liver tissue near bile ducts were observed and studied by light microscope and transmission election microscope. Results: By the limit of the safest endurance dose(50 Gy) of Bile duct, unreversed injury of the nuclei of liver cells occurred at 0 to 15 mm from bile duct revealed by transmission electron microscope and light microscope. The whole biliary duct wall would be undergone necrosis with irradiation dose over 60 Gy. Conclusions: Normal bile duct possesses good endurance to 192Ir-internal irradiation. Within the safest endurance limit of 50 Gy the effective irradiation field could reach 15 mm from the involved bile duct. (authors)

  3. Spirulina maxima prevents fatty liver formation in CD-1 male and female mice with experimental diabetes.

    Science.gov (United States)

    Rodríguez-Hernández, A; Blé-Castillo, J L; Juárez-Oropeza, M A; Díaz-Zagoya, J C

    2001-07-20

    The dietary administration of 5% Spirulina maxima (SM) during four weeks to diabetic mice, starting one week after a single dose of alloxan, 250 mg/Kg body weight, prevented fatty liver production in male and female animals. The main action of SM was on triacylglycerol levels in serum and liver. There was also a moderate hypoglycemia in male mice. The thiobarbituric acid reactive substances also decreased in serum and liver after SM administration. There was also a decrease in the percentage of HDL in diabetic mice that was reverted by the SM administration. The sum of LDL + VLDL percentages was also partially normalized in diabetic animals by the SM administration. An additional observation was the lower incidence of adherences between the liver and the intestine loops in the diabetic mice treated with SM compared with diabetic mice without SM. Male and female mice showed differences to diabetes susceptibility and response to SM, the female being more resistant to diabetes induction by alloxan and more responsive to the beneficial effects of SM. It is worth future work of SM on humans looking for better quality of life and longer survival of diabetic patients. PMID:11508645

  4. 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.

  5. The experimental study on liver VX-2 tumor by using MR diffusion-weighted imaging

    International Nuclear Information System (INIS)

    Objective: To study the imaging characteristics of rabbit's liver VX-2 tumor on MR diffusion-weighted imaging. Methods: Of the 35 New Zealand rabbits, 14 were implanted under the skin while 6 were implanted in liver with VX-2 tumor in preparing experiment, and 12 were implanted in liver and 3 as controls in formal experiment. Before and after the implantation, MR diffusion-weighted imaging (DWI), T1-weighted and T2-weighted images were performed respectively and periodically in 15 tumors including 12 liver tumor implantations in formal experiment. DWI parameters including apparent diffusion coefficient (ADC) value were acquired and statistically analyzed by SPSS 10.0. Results: (1) The successful rate of implantation was 29% (4/14) under the skin and 33% (2/6) in the liver in preparing experiment. And the successful rate of formal experiment was 83% (10/12). (2) DWI signal of VX-2 tumor was high and the signal became lower and lower with b value increased step by step. The signal of VX-2 tumor on ADC map was low. The ADC value of normal group was (2.57 ± 0.26) mm2/s (b=100 s/mm2 ) and (1.73 ± 0.31) mm2/s (b=300 s/mm2 ), and ADC value of VX-2 tumor group was (1.87 ± 0.25) mm2/s (b=100 s/mm2 ) and (1.57 ± 0.23) mm2/s (b=300 s/mm2 ), respectively.The F value of analysis of variance was 43.26 (P<0.001). The distinction of tumor ADC value in different b values was significant (P<0.05), and the distinction of ADC value between VX-2 tumor and normal liver was also significant (P<0.01). (3) VX-2 tumor developed quickly and metastasized early to all parts of the body, especially to the lung, the liver, the lymph nodes of mediastinum and so on. Conclusion: DWI signal of VX-2 tumor has its characteristic and DWI has important value in reflecting the movement of water molecules, discovering the VX-2 tumor, and tracking its progress. (authors)

  6. 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.

  7. Liver contrast enhancement by iohexol carrying liposomes - experimental study using digital imaging X-ray methods

    International Nuclear Information System (INIS)

    Iohexol-carrying liposomes are obtained by the method of detergent dialysis. The maximum iodine content in liposomes is 64.4%. The liposome suspension has been injected into rabbit auricular vein at a dose of 2 ml/min. Images of animal hepar are obtained before injection and after it at min 10, 20 and 30 under comparative standard conditions. Liver images have been taken by DSA-apparatus and CT-unit of III generation. The results show that synthesized liposomes accumulate in the liver parenchyma and account for enhancement of its image. It is believed that liposomes of the kind represent potentially new contrast media and further studies along these lines are justified regardless of their time-consuming nature. 7 refs

  8. Ultrastructural study of Kupffer cells in teleost liver under normal and experimental conditions.

    Science.gov (United States)

    Ferri, S; Sesso, A

    1981-01-01

    The Kupffer cells in the liver of the teleost fish, Pimelodus maculatus, are attached by desmosomes to the endothelial cells lining the sinusoids. These provide a strong attachment allowing them to resist the passage of blood. Following perfusion with India ink, both endothelial and Kupffer cells ingest India ink particles by pinocytosis and micropinocytosis. It is suggested that both cell types may represent two different functional states of the same cell. PMID:7296637

  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. 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

  11. 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

  12. 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.

  13. 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

  14. 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...

  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. 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.

  19. 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.

  20. Nimesulide aggravates redox imbalance and calcium dependent mitochondrial permeability transition leading to dysfunction in vitro

    International Nuclear Information System (INIS)

    Nimesulide (selective cyclooxygenase-2 inhibitor) is a nonsteroidal anti-inflammatory drug for the symptomatic treatment of painful conditions like osteoarthritis, spondilitis and primary dysmenorrhoea. Nimesulide induced liver damage is a serious side effect of this otherwise popular drug. The mechanism involved in nimesulide induced hepatotoxicity is still not fully elucidated. However, both mitochondrial dysfunction and oxidative stress have been implicated in contributing to liver injury in susceptible patients. Mitochondria besides being the primary source of energy, act as a hub of signals responsible for initiating cell death, irrespective of the pathway, i.e. apoptosis or necrosis. The present study was aimed to explore the role of compounding stress, i.e. Ca2+ overload and GSH depletion in nimesulide induced mitochondrial toxicity and dysfunction. Our study showed that, nimesulide (100 μM) treatment resulted into rapid depletion of GSH (60%) in isolated rat liver mitochondria and significant Ca2+ dependent MPT changed. Enhanced ROS generation (DCF fluorescence) was also observed in mitochondria treated with nimesulide. An important finding was that the concentration at which nimesulide oxidized reduced pyridine nucleotides (autofluorescence of NAD(P)H), it affected mitochondrial electron flow (MTT activity decreased by 75%) and enhanced mitochondrial depolarization significantly as assessed by Rhodamine 123 fluorescent probe. Therefore, nimesulide was found to aggravate redox imbalance and affect Ca2+ dependent mitochondrial membrane permeability transition leading to dysfunction and ultimately cell death.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    AIMS/HYPOTHESIS: Patients treated with metformin exhibit low levels of plasma vitamin B(12) (B(12)), and are considered at risk for developing B(12) deficiency. In this study, we investigated the effect of metformin treatment on B(12) uptake and distribution in rats. METHODS: Sprague Dawley rats (n...... = 18) were divided into two groups and given daily subcutaneous injections with metformin or saline (control) for three weeks. Following this, the animals received an oral dose of radio-labeled B(12) ((57)[Co]-B(12)), and urine and feces were collected for 24 h. Plasma, bowel content, liver, and...... kidneys were collected and analyzed for B(12), unsaturated B(12)-binding capacity, and (57)[Co]-B(12). RESULTS: Three weeks of metformin treatment reduced plasma B(12) by 22% or 289 [47-383] pmol/L (median and [range]) (p = 0.001), while no effect was observed on unsaturated B(12)-binding capacity...

  2. Experimental study of interventional infusion thermochemotherapy in rabbit liver VX2 tumor

    International Nuclear Information System (INIS)

    Objective: Effectiveness of two kinds of thermochemotherapy infusion from intraarterial approach were studied in the grafted liver VX2 tumors of rabbit. Methods: VX2 tumor model was established in 30 Newzland rabbit's livers. Percutaneous transfemoral hepatic arterial catheterization with fixation of the catheter tip inside the feeding vessel was carried out under DSA guidance. All 30 rabbits were divided into three groups (n=10 in each group), normal temperature 100 ml saline + Adriamycin (ADM) infusion (group 1), 60 degree C 100 ml saline + ADM continuous perfusion (group 2) and 60 degree C 100 ml saline + ADM intermittent perfusion (group 3). After the perfusion, the lasting time periods of 43-45 degree C for tumor tissue of group 2 and 3 together with the concentrations of ADM within tumor's tissue were measured. Results: Concentrations of ADM were shown as (12.013 ± 2.237) μg/ml, (17.622 ± 1.368) μg/ml, and (11.519 ± 1.225) μg/ml for group 2, group 3 and group 1 respectively. 60 degree C intermittent perfusion vs 60 degree C continuous perfusion showed P0.05. 43-45 degree C period lasting time (min) for 60 degree C continuous perfusion vs 60 degree C intermittent perfusion were (4.1 ± 2.7) min and (11.3 ± 3.3) min respectively, the latter was three times more than the former. There were no differences shown between the temperature, respiration and heart rate of group 2 and group 3. Conclusion: Intermittent intraarterial perfusion thermochemocherapy is a more effective interventional management among all thermochemotherapies. (authors)

  3. 915 MHz microwave ablation with implanted internal cooled-shaft antenna: Initial experimental study in in vivo porcine livers

    International Nuclear Information System (INIS)

    Purpose: To explore a preferred power output for further clinical application based on the ablated lesions induced by the four power outputs of 915 MHz microwave in experimental study of in vivo porcine livers. Materials and methods: A KY2000-915 microwave ablation system with an implanted 915 MHz internal cooled-shaft antenna was used in this study. A total of 24 ablations were performed in eight in vivo porcine livers. The energy was applied for 10 min at microwave output powers of 50 W, 60 W, 70 W, and 80 W. Long-axis and short-axis diameters of the coagulation zone were measured on all gross specimens. Results: The shapes of the 915 MHz microwave ablation lesions were elliptical commonly. As the power increased, the long-axis and short-axis diameters of the coagulation zone had a tendency to rise. But the long-axis diameter of the ablated lesion at 50 W was not significantly smaller than that of the ablated lesion at 60 W (P > 0.05) and there were no statistical differences in short-axis diameters of the ablated lesion among the three power outputs of 60 W, 70 W and 80 W (P > 0.05). After 10 min irradiation of 60 W, the long-axis and short-axis diameters of the coagulation zone were 5.02 ± 0.60 cm and 3.65 ± 0.46 cm, respectively. Conclusions: For decreasing the undesired damages of liver tissues along the shaft and the number of antenna in further clinically percutaneous microwave ablation treatment, the power of 60 W may be a preferred setting among the four power outputs used in present study.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    severity on Danish roads by examining a comprehensive set of accidents involving a cyclist and a collision partner between 2007 and 2011. Method: This study estimates a generalized ordered logit model of the severity of cyclist injuries because of its ability to accommodate the ordered-response nature of......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 while relaxing the proportional odds assumption. Results: Model estimates show that cyclist fragility (children under 10 years old and elderly cyclists over 60 years of age) and cyclist intoxication are aggravating individual factors,while helmet use is a mitigating factor. Speed limits above 70...

  5. 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...

  6. 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...

  7. 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...

  8. 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

  9. Micro-CT Based Experimental Liver Imaging Using a Nanoparticulate Contrast Agent: A Longitudinal Study in Mice

    OpenAIRE

    Boll, Hanne; Nittka, Stefanie; Doyon, Fabian; Neumaier, Michael; Marx, Alexander; Kramer, Martin; Groden, Christoph; Brockmann, Marc A.

    2011-01-01

    Background Micro-CT imaging of liver disease in mice relies on high soft tissue contrast to detect small lesions like liver metastases. Purpose of this study was to characterize the localization and time course of contrast enhancement of a nanoparticular alkaline earth metal-based contrast agent (VISCOVER ExiTron nano) developed for small animal liver CT imaging. Methodology ExiTron nano 6000 and ExiTron nano 12000, formulated for liver/spleen imaging and angiography, respectively, were intra...

  10. 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...

  11. 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

  12. Effects of phospholipid hepatoprotectors on apoptosis during experimental liver pathology induced by isoniazid and paracetamol.

    Science.gov (United States)

    Udut, V V; Vengerovsky, A I; Dygai, A M

    2013-03-01

    Phospholipid hepatoprotectors essentiale, eplir, and their combinations with succinic acid decreased the relative content of apoptotic lymphocytes and granulocytes in the blood, content of TNF-α, total and indirect bilirubin, and activities of transaminases and alkaline phosphatase and increase the content of IL-10 in rats with experimental intoxication induced by isoniazid and paracetamol. A combination of eplir and succinic acid was most effective in preventing the development of leukocyte apoptosis. PMID:23658881

  13. 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.

  14. 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

  15. 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

  16. Experimental characterization of the mechanism of perfluorocarboxylic acids' liver protein bioaccumulation: the key role of the neutral species.

    Science.gov (United States)

    Woodcroft, Mark W; Ellis, David A; Rafferty, Steven P; Burns, Darcy C; March, Raymond E; Stock, Naomi L; Trumpour, Kyle S; Yee, Janet; Munro, Kim

    2010-08-01

    Perfluorocarboxylic acids (PFCAs) of chain length greater than seven carbon atoms bioconcentrate in the livers of fish. However, a mechanistic cause for the empirically observed increase in the bioconcentration potential of PFCAs as a function of chain length has yet to be determined. To this end, recombinant rat liver fatty acid-binding protein (L-FABP) was purified, and its interaction with PFCAs was characterized in an aqueous system at pH 7.4. Relative binding affinities of L-FABP with PFCAs of carbon chain lengths of five to nine were established fluorimetrically. The energetics, mechanism, and stoichiometry of the interaction of perfluorooctanoic acid (PFOA) with L-FABP were examined further by isothermal titration calorimetry (ITC) and electrospray ionization combined with tandem mass spectrometry (ESI-MS/MS). Perfluorooctanoic acid was shown to bind to L-FABP with an affinity approximately an order of magnitude less than the natural ligand, oleic acid, and to have at least 3:1 PFOA:L-FABP stoichiometry. Two distinct modes of PFOA binding to L-FABP were observed by ESI-MS/MS analysis; in both cases, PFOA binds solely as the neutral species under typical physiological pH and aqueous concentrations of the anion. A comparison of their chemical and physical properties with other well-studied biologically relevant chemicals showed that accumulation of PFCAs in proteins as the neutral species is predictable. For example, the interaction of PFOA with L-FABP is almost identical to that of the acidic ionizing drugs ketolac, ibuprofen, and warfarin that show specificity to protein partitioning with a magnitude that is proportional to the K(OW) (octanol-water partitioning) of the neutral species. The experimental results suggest that routine pharmacochemical models may be applicable to predicting the protein-based bioaccumulation of long-chain PFCAs. PMID:20821618

  17. 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 ...

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. Experimental induction of liver fibrosis in young guinea pigs by combined application of copper sulphate and aflatoxin B1.

    Science.gov (United States)

    Seffner, W; Schiller, F; Lippold, U; Dieter, H H; Hoffmann, A

    1997-08-22

    Aflatoxin B1 alone (0.05 mg resp. 0.037 mg/kg/d), copper alone (6.6 mg/kg/d or 200 mg/l drinking water) or a combination of both was administered orally for 6 months to young guinea pigs from the first/second day of life. In the copper group there were no pathomorphological changes. For the aflatoxin B1 group, liver damage was established. In the combined group, liver injury was more frequent and more severe compared to the aflatoxin B1 group and biliary copper excretion was diminished compared with the copper group. Histologically, only the livers of this group exhibited degeneration, atrophy and steatosis of liver cells, inflammatory processes and a more or less prominent fibrosis. For childhood cirrhosis (ICC and ICT) a combined etiology--a liver damaging agent plus elevated alimentary copper--is a plausible hypothesis. PMID:9334826

  3. 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

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

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    Jie Wu

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

  5. [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

  6. 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 are not....... RESULTS: RSV reduced the development of histological steatosis (P = 0.03) and partly triglyceride accumulation (fold change reduced from 3.6 to 2.4, P = 0.08) in the male NAFL model, though effects were moderate. In NASH prevention, RSV reduced the accumulation of triglyceride in hepatic tissue (P < 0...... that a weak hepatic benefit of RSV treatment is seen in prevention of steatosis only. This article is protected by copyright. All rights reserved....

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

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    Han Bing

    2012-05-01

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

  8. Experimental study of treatment on rabbit liver VX2 tumor by selective hepatic artery embolization hyperthermia with nano superparamagnetic iodized oil

    International Nuclear Information System (INIS)

    Objective: To observe the therapeutic response of liver tumors by arterial embolization hyperthermia with Nano Superparamagnetic Iodized Oil (NSIO) using rabbit VX2 liver tumor model. Methods: A total 24 rabbits containing experimental hepatic tumors were randomly assigned to one of four groups as follows: NSIO embolization hyperthermia group (group A), Lipidol embolization group (group B), NSIO embolization group (group C), and control group (group D), each groups contain 6 VX2 rabbits. Fourteen days after implantation of the experimental hepatic tumor, VX2 rabbits were treated. In group A group B and group C, the rabbits hepatic proper artery were selectively catheterized by 3 Fr microcatheters via right femoral artery under fluoroscopic guidance. 10% NSIO 0.5 ml (group A and group C) or Lipidol 0.5 ml(group B) infused into proper hepatic artery. Three days after embolization, the rabbits in group A and group B were exposed to gap-type alternating magnetic field for 30 minutes, while rabbits in group C and group D have not been exposed to alternating magnetic field. The liver tumor size were measured by CT scanning before and 14 days after treatment then the animals were sacrificed, the liver, lung, heart spleen and kidney were harvested for histopathology examination, the liver tumor size were detected directly. Results: All subjects experienced uneventful 14 days survivals, on the biochemical examination, there were no changes about the function of liver and renal in each group 14 days after treatment compare to pre- treatment. Fourteen days after treatment, the tumor size decreased by 8.09% in group A, but increased by 9.72% and 13.00% (P<0.05) in group B and group C respectively, in group D, the tumor size increased by 57.50% (P<0.01). In histopathology examination, the tumor necrosis in three treatment groups were manifest, particular in group A. Conclusion: Arterial embolization hyperthermia with NSIO has obvious therapeutic response to experimental hepatic

  9. [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

  10. The Value of Proton Magnetic Resonance Spectroscopy in High-Intensity Focused Ultrasound Treatment of Experimental Liver Cancer

    Directory of Open Access Journals (Sweden)

    Zhuo-yue Tang

    2015-06-01

    Full Text Available High-intensity focused ultrasound (HIFU is a rapidly developing, non-invasive technique for local treatment of solid tumors that produce coagulative tumor necrosis. This study is aimed to investigate the feasibility of proton magnetic resonance spectroscopy (MRS on early assessing treatment of HIFU ablation in rabbit with VX2 liver tumor. HIFU ablation was performed on normal liver and VX2 tumor in rabbit, and MRS was performed on normal liver and VX2 tumor before and 2 days after 100% HIFU ablation or 80% ablation in tumor volume. Choline (Cho and choline/lipid (Cho/Lip ratios between complete and partial HIFU ablation of tumor were compared. Tissues were harvested and sequentially sliced to confirm the necrosis. In normal liver, the Cho value liver was not obviously changed after HIFU (P > .05, but the Cho/Lip ratio was decreased (P .05; however, the Cho value in partial ablation was still higher than that in normal liver before or in tumor after complete HIFU treatment due to the residual part of tumors, and Cho/Lip ratio is lower than that in complete HIFU treatment (P < .001. The changes in MRS parameters were consistent with histopathologic changes of the tumor tissues after treatment. MRS could differentiate the complete tumor necrosis from residual tumor tissue, when combined with magnetic resonance imaging. We conclude that MRS may be applied as an important, non-invasive biomarker for monitoring the thoroughness of HIFU ablation.

  11. STAT3, a Key Parameter of Cytokine-Driven Tissue Protection during Sterile Inflammation – the Case of Experimental Acetaminophen (Paracetamol)-Induced Liver Damage

    Science.gov (United States)

    Mühl, Heiko

    2016-01-01

    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 toward a fatal condition. Focused administration of recombinant STAT3-activating cytokines may evolve as novel therapeutic approach under those ill-fated conditions. PMID:27199988

  12. 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.

  13. 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

    -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 or...

  14. Influence of Prescribed Herbal and Western Medicine on Patients with Abnormal Liver Function Tests: A Retrospective Quasi-Experimental Study

    Directory of Open Access Journals (Sweden)

    Lee Ah-Ram

    2012-03-01

    Full Text Available Objectives: The aim of this study was to investigate the safety and the efficacy of Korean herbal, western and combination medicine use in patients with abnormal liver function tests. Methods: We investigated nerve disease patients with abnor-mal liver function tests who were treated with Korean herbal, western and combination medicine at Dong-Eui University Oriental Hospital from January 2011 to August 2011. We co-mpared aspartic aminotransferase (AST, alanine aminotran-sferase (ALT, alkaline phosphatase (ALP and total bilirubin (T-bil levels before and after taking medicine and excluded patients who had liver-related disease when admitted. Results: AST and ALT were decreased significantly in patients who had taken herbal, western medicine. AST, ALT and ALP were decreased significantly in patients who had taken comb-ination medicine. Compare to herbal medicine, AST, ALT and ALP were decreased significantly in patients who had taken western medicine, and ALT and ALP were decreased signifi-cantly in patients who had taken combination medicine. There were no significant differences between western and combin-ation medicine. Conclusions: This study suggests that prescribed Korean herbal medicine, at least, does not injure liver function for patients’, moreover, it was shown to be effective in patients with abnormal liver function tests.

  15. 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

  16. 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.

  17. Determination of regional flow by use of intravascular PET tracers: microvascular theory and experimental validation for pig livers

    DEFF Research Database (Denmark)

    Munk, O L; Bass, L; Feng, H;

    2003-01-01

    with the standard model in a pig liver study. METHODS: Eight pigs underwent a 5-min dynamic PET study after (15)O-carbon monoxide inhalation. Throughout each experiment, hepatic arterial blood and portal venous blood were sampled, and flow was measured with transit-time flow meters. The hepatic dual...... activity after an intravascular tracer bolus injection. The microvascular models include only parameters with a clear-cut physiologic interpretation and are applicable to capillary beds in any organ. In this study, the microvascular models were validated for the liver and provided quantitative regional...

  18. 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.

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

    DEFF Research Database (Denmark)

    Andersen, Louise Bjørkholt; Przybyl, Lukasz; Haase, Nadine; von Versen-Höynck, Frauke; Qadri, Fatimunnisa; Jørgensen, Jan Stener; Sorensen, Grith Lykke; Fruekilde, Palle; Poglitsch, Marko; Szijarto, István; Gollasch, Maik; Peters, Joerg; Muller, Dominik N; Christesen, Henrik Thybo; Dechend, Ralf

    2015-01-01

    BACKGROUND: We tested the controversial hypothesis that vitamin D depletion aggravates hypertension and target-organ damage by influencing renin. METHODS AND RESULTS: Four-week-old double-transgenic rats (dTGR) with excess angiotensin (Ang) II production due to overexpression of the human renin (h......REN) and angiotensinogen (hAGT) genes received vitamin D-depleted (n=18) or standard chow (n=15) for 3 weeks. The depleted group had very low serum 25-hydroxyvitamin D levels (mean±SEM; 3.8±0.29 versus 40.6±1.19 nmol/L) and had higher mean systolic BP at week 5 (158±3.5 versus 134.6±3.7 mm Hg, P<0......, hREN, and rRen were increased by vitamin D depletion. Regulatory T cells in the spleen and in the circulation were not affected. Ang metabolites, including Ang II and the counter-regulatory breakdown product Ang 1 to 7, were significantly up-regulated in the vitamin D-depleted groups, while ACE-1...

  20. Acute Effects of Liver Vein Occlusion by Stent-Graft Placed in Transjugular Intrahepatic Portosystemic Shunt Channel: An Experimental Study

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the effects of hepatic vein occlusion by stent-graft used in transjugular intrahepatic portosystemic shunt (TIPS). The experiments were performed in six healthy pigs under general anesthesia. Following percutaneous transhepatic implantation of a port-a-cath in the right hepatic vein, TIPS was created with a stent-graft (Viatorr; W L Gore, Flagstaff, AZ, USA). The outflow from the hepatic vein, blocked by the stent-graft was documented by injection of contrast medium and repeated injections of 99Tcm-labeled human serum albumin through the port-a-cath. After 2 weeks, the outflow was re-evaluated, the pigs were sacrificed, and histopathologic examination of the liver was performed. Occlusion of the hepatic vein by a stent-graft had a short and temporary effect on the outflow. Histopathological examination from the affected liver segment showed no divergent pattern. Stent-grafts used in TIPS block the outflow from the liver vein, but do not have a prolonged circulatory effect and do not affect the liver parenchyma

  1. 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

  2. Naproxen aggravates doxorubicin-induced cardiomyopathy in rats

    Directory of Open Access Journals (Sweden)

    Pathan Rahila

    2010-01-01

    Full Text Available Background : The repercussion of the heated dispute on cyclooxygenase-2 (COX-2 selective nonsteroidal anti-inflammatory drugs (NSAIDs led to the national and international withdrawal of several of the recently introduced coxibs. Further debate and research have highlighted risks of the classical NSAIDs too. There is much controversy about the cardiovascular safety of a nonselective NSAID naproxen (NAP and its possible cardioprotective effect. Objectives : The study was undertaken to determine the cardiovascular effects of NAP on doxorubicin-induced cardiomyopathy in rats. Materials and Methods : Male albino rats received a single i.p. injection of normal saline (normal control group and doxorubicin (DOX 15 mg/kg (toxic control group. Naproxen was administered alone (50 mg/kg/day, p.o. and in combination with DOX and DOX + trimetazidine (TMZ (10 mg/kg/day, p.o. for 5 days after 24 h of DOX treatment. DOX-induced cardiomyopathy was assessed in terms of increased activities of serum lactate dehydrogenase (LDH, tissue thiobarbituric acid reactive substances (TBARS and decreased activities of myocardial glutathione, superoxide dismutase and catalase, followed by transmission electron microscopy of the cardiac tissue. Results : Doxorubicin significantly increased oxidative stress as evidenced by increased levels of LDH and TBARS and decreased antioxidant enzymes levels. Both biochemical and electron microscopic studies revealed that NAP itself was cardiotoxic and aggravated DOX-induced cardiomyopathy and abolished the protective effect of TMZ in rats. Conclusions : This study indicates that NAP has the potential to worsen the situation in patients with cardiovascular disease. Therefore, it should be used cautiously in patients with compromised cardiac function.

  3. 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.

  4. 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

  5. In situ hybridization of hepatitis C virus RNA in liver cells of an experimentally infected rhesus macaque

    Directory of Open Access Journals (Sweden)

    Selma Majerowicz

    2004-10-01

    Full Text Available The liver tissue of a rhesus macaque inoculated with hepatitis C virus (HCV has been analyzed for the presence of HCV RNA using the technique of in situ hybridization, both at light and electron microscopy levels. The animal was inoculated by the intrasplenic route using a HCV infected autogenic hepatocyte transplant. The serum sample used to infect the hepatocyte cells was characterized by polymerase chain reaction technique and shown to be positive for HCV RNA, genotype 3 with 10(7 RNA copies/ml. In situ hybridization was performed using a complementary negative strand probe made with the specific primer. We were able to detect and localize viral RNA in altered membranes of the rough endoplasmic reticulum of infected liver cells, showing evidence of virus replication in vivo.

  6. 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)

  7. 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.

  8. 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

  9. 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.

  10. Liver metastases

    Science.gov (United States)

    Metastases to the liver; Metastatic liver cancer; Liver cancer - metastatic ... Almost any cancer can spread to the liver. Cancers that can ... Lung cancer Melanoma Pancreatic cancer Stomach cancer The risk ...

  11. 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 ...

  12. 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

  13. 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

  14. 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

  15. Protective effect of L-arginine against necrosis and apoptosis induced by experimental ischemic and reperfusion in rat liver

    International Nuclear Information System (INIS)

    To study the effect of L-arginine on apoptosis and necrosis induced by 1-h ischemia followed by 3-h reperfusion. Adult Wistar rats underwent 60 min of partial liver ischemia followed by 3-h reperfusion. Eighteen Wistar rats were divided into sham-operated control group (1) ( n = 6), ischemia and reperfusion (I/R) group (0.9 % saline (5 ml/kg, orally) for 7 days) (2) ( n 6), and L-arginine-treated group (10 mg/kg body weight daily orally for 7 days before inducing ischemia-reperfusion maneuver) (3) ( n = 6). Apoptotic and necrotic hepatocytes, nitric oxide levels in hepatocytes, Bcl-2 mRNA, and Bcl-2 protein were measured. Liver injury was assessed by plasma alanine transaminases (ALT), aspartate transaminases (AST), liver histopathology, and electron microscopy. An ischemic and reperfusion hepatocellular injury occurred as was indicated by increased serum ALT, AST, histopathology, and electron microscopy. Apoptosis and necrosis associated marker gene Bcl-2 mRNA and protein expression were decreased in I/R group. Pretreatment with L-arginine significantly decreased serum ALT and AST level and apoptotic and necrotic cells after 1 h ischemia followed by 3 h of reperfusion. Nitric oxide production in hepatocytes was increased twofold by L-arginine treatment when compared with I/R group. Histopathology and transmission electron microscopy (TEM) studies showed markedly diminished hepatocellular injury in L-arginine-pretreated rats during the hepatic I/R. Thus, it may be concluded that L-arginine afforded significant protection from necrosis and apoptosis in I/R injury by upregulated Bcl-2 gene and nitric oxide production. (author)

  16. 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

  17. 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

  18. Overlapping ablation using a coaxial radiofrequency electrode and multiple cannulae system: experimental study in ex-vivo bovine liver

    International Nuclear Information System (INIS)

    To assess the sizes and configurations of thermal zones after overlapping ablations using a coaxial radiofrequency (RF) electrode and multiple cannulae in ex-vivo bovine liver. For ablation procedures, a coaxial RF electrode and introducer set was used. Employing real-time ultrasound guidance and overlapping techniques in explanted, fresh bovine liver, we created five kinds of thermal zones with one (n=10), two (n=8), four (n=3), and six ablation spheres (n=3). Following ablation, MR images were obtained and the dimensions of all thermal zones were measured on the longitudinal or transverse section of specimens. The shape of the composite ablation zones was evaluated using three-dimensional MR image reconstruction. At gross pathologic examination of ten single-ablation zones (spheres), the long-axis (transverse) and short-axis lengths of zones ranged from 3.7 to 4.4 (mean, 4.1) cm and from 3.5 to 4.0 (mean, 3.7) cm, respectively. The long-axis (transverse) and short-axis lengths of double-ablation zones (cylinders) with 23% overlap ranged from 7.0 to 7.7 (mean, 7.3) cm and from 3.0 to 3.9 (mean, 3.5) cm, respectively; those with 58% overlap ranged from 6.0 to 6.4 (mean, 6.2) cm and from 3.8 to 4.6 (mean, 4.3) cm, respectively. The long-axis (diagonal) and short-axis lengths on a transverse section of four-ablation zones (cakes) ranged from 8.5 to 9.7 (mean, 9.1) cm and from 3.0 to 4.1 (mean, 3.7) cm, respectively. Gross pathologic examination of three composite six-ablation zones (spheres) showed that the long-axis (diagonal) and short-axis lengths of zones ranged from 9.0 to 9.9 (mean, 9.4) cm and from 6.8 to 7.5 (mean, 7.2) cm, respectively. T2-weighted MR images depicted low-signal thermal zones containing multiple curvilinear and spotty regions of hyperintensity. Using a coaxial RF electrode and multiple cannulae, together with ultrasound guidance and precise overlapping ablation techniques, we successfully created predictable thermal zones in ex-vivo bovine

  19. 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

  20. 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.

  1. 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.

  2. 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 ...

  3. 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 ...

  4. Liver fibrosis

    OpenAIRE

    Bataller, Ramón; Brenner, David A.

    2005-01-01

    Liver fibrosis is the excessive accumulation of extracellular matrix proteins including collagen that occurs in most types of chronic liver diseases. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension and often requires liver transplantation. Our knowledge of the cellular and molecular mechanisms of liver fibrosis has greatly advanced. Activated hepatic stellate cells, portal fibroblasts, and myofibroblasts of bone marrow origin have been identified as major ...

  5. No aggravation of the course of experimental glomerulonephritis in spontaneously hypertensive rats.

    OpenAIRE

    Stein, H. D.; Sterzel, R. B.; Hunt, J D; Pabst, R; Kashgarian, M.

    1986-01-01

    Functional and morphologic glomerular alterations induced by antiglomerular basement membrane (anti-GBM) nephritis were investigated in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto controls (WKY) for assessment of the role of systemic hypertension in immunologically mediated renal injury. Over a 6-week period serial measurements of systolic blood pressure (BP), serum creatinine (SCreat), creatinine clearance (CCreat), and urinary albumin excretion (UAlbV) were obtained ...

  6. 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.

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

    DEFF Research Database (Denmark)

    Nobili, Elena; Salvado, M Dolores; Folkersen, Lasse Westergaard; Castiglioni, Laura; Kastrup, Jens; Wetterholm, Anders; Tremoli, Elena; Hansson, Göran K; Sironi, Luigi; Haeggström, Jesper Z; Gabrielsen, Anders

    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...

  8. 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

  9. 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.

  10. 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.

  11. 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.)

  12. 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.)

  13. 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...

  14. 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…

  15. 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)...

  16. 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)

  17. 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...

  18. 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.

  19. [Experimental Approach to Analysis of the Relationship between Food Environments and Lifestyle-Related Diseases, Including Cardiac Hypertrophy, Fatty Liver, and Fatigue Symptoms].

    Science.gov (United States)

    Horiuchi, Masahisa; Nakakuma, Miwa; Arimura, Emi; Ushikai, Miharu; Yoshida, Goichiro

    2015-01-01

    The food habit is involved in the onset and development of lifestyle-related diseases. In this review I would like to describe a historical case of vitamin B1 deficiency, as well as our case study of fatty acid metabolism abnormality due to carnitine deficiency. In history, the army and navy personnel in Japan at the end of the 19th century received food rations based on a high-carbohydrate diet including white rice, resulting in the onset of beriberi. An epidemiological study by Kenkan Takaki revealed the relationship between the onset of beriberi and rice intake. Then, Takaki was successful in preventing the onset of beriberi by changing the diet. However, the primary cause had yet to be elucidated. Finally, Christian Eijkman established an animal model of beriberi (chickens) showing peripheral neuropathy, and he identified the existence of an anti-beriberi substance, vitamin B1. This is an example of the successful control of a disease by integrating the results of epidemiological and experimental studies. In our study using a murine model of fatty acid metabolism abnormality caused by carnitine deficiency, cardiac abnormality and fatty liver developed depending on the amount of dietary fat. In addition, the mice showed disturbance of orexin neuron activity related to the sleep-arousal system, which is involved in fatigue symptoms under fasting condition, one of the states showing enhanced fatty acid metabolism. These findings suggest that fatty acid toxicity is enhanced when the mice are more dependent on fatty acid metabolism. Almost simultaneously, a human epidemiological study showed that narcolepsy, which is caused by orexin system abnormality, is associated with the polymorphism of the gene coding for carnitine palmitoyltransferase 1B, which is involved in carnitine metabolism. To understand the pathological mechanism of fatty acid toxicity, not only an experimental approach using animal models, but also an epidemiological approach is necessary. The

  20. Evaluation of the liver function for patients with chronic liver diseases using 99mTc-galactosyl human serum albumin [99mTc-GSA] liver scintigraphy

    International Nuclear Information System (INIS)

    99mTc-galactosyl human serum albumin [99mTc-GSA] is a new scintigraphic agent which binds specifically to asialoglycoprotein-receptor on the hepatic cell membrane. The new liver scintigraphy using 99mTc-GSA was performed in 30 patients with chronic liver disease to evaluate the residual liver function. Two parameters were obtained from 99mTc-GSA time activity curves of both the heart and the liver. One was [HH15] (clearance index), which was the ratio of radioactivity of the liver at 15 min over that at 3 min after injection. The other was [LHL15] (receptor index), the ratio of radioactivity of the liver over that of the liver plus heart at 15 min. Significant decrease in LHL15 and increase in HH15 value were observed in accordance with severities of the liver damage and clinical aggravation. These parameters correlated significantly with Child-Pugh score, glucagon test, ICG-R15, serum albumin levels, cholinesterase, prothrombin time and hepaplastin test also. In conclusion, these findings indicate that 99mTc-GSA liver scintigraphy is useful for evaluating the liver flunction in patients with chronic liver disease. (author)

  1. 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...

  2. 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

  3. Liver biopsy

    Science.gov (United States)

    Biopsy - liver; Percutaneous biopsy ... prevent pain or to calm you (sedative). The biopsy may be done through the abdominal wall: You ... provider will find the correct spot for the biopsy needle to be inserted into the liver. This ...

  4. Liver Diseases

    Science.gov (United States)

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

  5. 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. ...

  6. 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

  7. Quantitative hepatosplenic scintiscanning. Experimental and clinical studies to determine the contents of radioactivity in liver and spleen following administration of 99mTc sulfur colloid

    International Nuclear Information System (INIS)

    Hepatosplenic scintiscans were obtained from 78 patients following administration of 99mTc sulfur colloid using a double-head scanner and subjected to quantitative analysis. It was the aim of the study to assess the practicability of quantitative scintiscanning of liver and spleen, to define the range of generally acceptable, normal values for the concentration of 99mTc sulfur colloid in liver and spleen as well as to evaluate the clinical relevance of this method. The following values were determined to be normal: 4.7±1.5 for the liver: Spleen ratio; 31±3% for the proportion of the left hepatic lobe in total liver concentration; 68.7±5.4% and 17.4±3.6% for the active contents of liver and spleen, respectively. Quantitative scintiscanning constitutes a very sensitive method to detect transformation processes in the liver that are associated with a decreased liver: Spleen ratio and an increased ratio between the left hepatic lobe and the total organ. The method is unsuitable to assess pathological accumulation of the tracer substances. The question as to whether the use of the more time-consuming procedure of quantitative scintiscanning is justified by the additional diagnostic information gained remains to be investigated in further studies. (TRV)

  8. 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...

  9. Does International Mobility of High-Skilled Workers Aggravate Between-Country Inequality ?

    OpenAIRE

    Grossmann, Volker; Stadelmann, David

    2010-01-01

    This paper analyzes the interaction of international migration of high-skilled labor and relative wage income between source and destination economies of expatriates. We develop an overlapping-generations model with increasing returns which suggests that international integration of the market for skilled labor aggravates between-country inequality by harming those which are source economies to begin with while benefiting host economies. The result is robust to allowing governments to optimal...

  10. 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.

  11. High Elmo1 expression aggravates and low Elmo1 expression prevents diabetic nephropathy

    OpenAIRE

    Hathaway, Catherine K.; Chang, Albert S.; Grant, Ruriko; Kim, Hyung-Suk; Madden, Victoria J.; Bagnell, C. Robert; Jennette, J. Charles; Smithies, Oliver; Kakoki, Masao

    2016-01-01

    About one-third of patients with type 1 diabetes mellitus develop nephropathy, which often progresses to end-stage renal diseases. The present study demonstrates that below-normal Elmo1 expression in mice ameliorates the albuminuria and glomerular histological changes resulting from long-standing type 1 diabetes, whereas above-normal Elmo1 expression makes both worse. Increasing Elmo1 expression leads to aggravation of oxidative stress markers and enhances the expression of fibrogenic genes. ...

  12. Liver resections for liver transplantations

    OpenAIRE

    2010-01-01

    Split-Liver and living-related donor liver transplantation are the newest and both technically and ethically most challenging developments in liver transplantation and have contributed to a reduction in donor shortage. We report the technical aspects of surgical procedures performed to achieve a partial graft from a cadaveric and a live donor.

  13. 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.

  14. 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

    International Nuclear Information System (INIS)

    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

  15. 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.

  16. 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

  17. Benign Liver Tumors

    Science.gov (United States)

    ... Handouts Education Resources Support Services Helpful Links For Liver Health Information Call 1-800-GO-LIVER (1- ... Liver > Liver Disease Information > Benign Liver Tumors Benign Liver Tumors Explore this section to learn more about ...

  18. 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...

  19. 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

  20. 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.

  1. Liver scintigraphy

    International Nuclear Information System (INIS)

    Liver scintigraphy can be classified into 3 major categories according to the properties of the radiopharmaceuticals used, i.e., methods using radiopharmaceuticals which are (1) incorporated by hepatocytes, (2) taken up by reticulo endothelial cells, and (3) distributed in the blood pool of the liver. Of these three categories, the liver scintigraphy of the present research falls into category 2. Radiopharmaceuticals which are taken up by endothelial cells include 198Au colloids and 99mTc-labelled colloids. Liver scintigraphy takes advantage of the property by which colloidal microparticles are phagocytosed by Kupffer cells, and reflect the distribution of endothelial cells and the intensity of their phagocytic capacity. This examination is indicated in the following situations: (i) when you suspect a localized intrahepatic lesion (tumour, abscess, cyst, etc.), (ii) when you want to follow the course of therapy of a localized lesion, (iii) when you suspect liver cirrhosis, (iv) when you want to know the severity of liver cirrhosis or hepatitis, (v) when there is hepatomegaly and you want to determine the morphology of the liver, (vi) differential diagnosis of upper abdominal masses, and (vii) when there are abnormalities of the right diaphragm and you want to know their relation to the liver

  2. 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

  3. 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

  4. 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

  5. Lipoxin A4 exerts protective effects against experimental acute liver failure by inhibiting the NF-κB pathway.

    Science.gov (United States)

    Jiang, Xueqiang; Li, Zhihao; Jiang, Shengfang; Tong, Xuefei; Zou, Xiaojing; Wang, Wan; Zhang, Zhengang; Wu, Liang; Tian, Deying

    2016-03-01

    Although rare, acute liver failure (ALF) is associated with high levels of mortality, warranting the development of novel therapies. Nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) play roles in ALF. Lipoxin A4 (LXA4) has been shown to alleviate inflammation in non-hepatic tissues. In the present study, we explored whether LXA4 exerted hepatoprotective effects in a rat model of ALF. A rat model of ALF was generated by intraperitoneal injections of D-galactosamine (300 mg/kg) and lipopolysaccharide (50 µg/kg). Animals were randomly assigned to: control group (no ALF); model group (ALF); and the groups treated with a low dose (0.5 µg/kg), medium dose (1 µg/kg), and high dose (2 µg/kg) of LXA4 (all with ALF); and pyrrolidine dithiocarbamate (PDTC)-treated group (ALF and 100 mg/kg PDTC, an inhibitor of NF-κB). Liver histology was measured using H&E staining, serum levels by ELISA, and liver mRNA expression was measured by RT-PCR for the detection of the pro‑inflammatory cytokines TNF-α and IL-6. Liver cell apoptosis (as measured using the TUNEL method and examining caspase-3 activity), and Kupffer cell NF-κB activity [using an electrophoretic mobility shift assay (EMSA)] were examined. Serum levels of transaminases, TNF-α and interleukin-6 (IL-6) were substantially higher in the model group compared to controls. In the model group, significant increases in TNF-α and IL-6 mRNA expression, TUNEL‑positive cells, and caspase-3 activity in the liver tissue were noted. LXA4 improved liver pathology and significantly decreased the indicators of inflammatory response and apoptosis in a dose-dependent manner. High-dose LXA4 provided better protection than PDTC. LXA4 administration significantly decreased NF-κB expression in hepatocytes and Kupffer cells. These results indicated that LXA4 inhibited NF-κB activation, reduced the secretion of pro-inflammatory cytokines, and inhibited apoptosis of liver cells

  6. Liver-Regenerative Transplantation: Regrow and Reset.

    Science.gov (United States)

    Collin de l'Hortet, A; Takeishi, K; Guzman-Lepe, J; Handa, K; Matsubara, K; Fukumitsu, K; Dorko, K; Presnell, S C; Yagi, H; Soto-Gutierrez, A

    2016-06-01

    Liver transplantation, either a partial liver from a living or deceased donor or a whole liver from a deceased donor, is the only curative therapy for severe end-stage liver disease. Only one-third of those on the liver transplant waiting list will be transplanted, and the demand for livers is projected to increase 23% in the next 20 years. Consequently, organ availability is an absolute constraint on the number of liver transplants that can be performed. Regenerative therapies aim to enhance liver tissue repair and regeneration by any means available (cell repopulation, tissue engineering, biomaterials, proteins, small molecules, and genes). Recent experimental work suggests that liver repopulation and engineered liver tissue are best suited to the task if an unlimited availability of functional induced pluripotent stem (iPS)-derived liver cells can be achieved. The derivation of iPS cells by reprogramming cell fate has opened up new lines of investigation, for instance, the generation of iPS-derived xenogeneic organs or the possibility of simply inducing the liver to reprogram its own hepatocyte function after injury. We reviewed current knowledge about liver repopulation, generation of engineered livers and reprogramming of liver function. We also discussed the numerous barriers that have to be overcome for clinical implementation. PMID:26699680

  7. Experimental study of bleeding control on liver biopsy in rabbit: N-butyl 2-cyanoacrylate(NBCA) injection and RF electrocauterization

    International Nuclear Information System (INIS)

    To evaluate the hemostatic effect of N-butyl 2-cyanoacrylate(NBCA) injection and RF electrocauterization of the tract after fine needle biopsy of the liver, and the histopathologic changes of the liver. Three lobes of rabbit liver were selected and separately punctured four times with 21 gauge biopsy needles. According to the hemostatic procedure on fine needle biopsy, three groups (1, 2, 3) were found : group 1, in which there was no maneuver for bleeding control, was the control group; group 2, in which NBCA was injected into the puncture tract while slowly removing the needle; group 3, in which RF electrocauterization of the tract was carried out. After completely removing the needle, each group was evaluated for amount of bleeding and histologic change. The amount of bleeding was 0.407gm ±0.245 in group 1, 0.028gm ± 0.036 in group 2 and 0.035gm ±0.028 in group 3. As compared with the control group(group 1), injecting NBCA into the biopsy tract(P=0.0002) and RF electrocauterization of the tract(P=0.0003) significantly reduced the amount of bleeding after liver biopsy. The amount of bleeding was not statistically different between group 2 and 3, however (P=0.58). In Group 1, the tract was fully filled with blood. Group 2 showed NBCA embolized in the biopsy tract, adhering to hepatocytes and mixed with blood; small vessels adjacent to the puncture tract were filled with NBCA. Group 3 showed tissue degeneration, including necrosis of hepatocytes, vacuolation and neutrophil infiltration. Injection of NBCA and RF electrocauterization of the tract after puncture of the liver for biopsy efficiently controlled bleeding. In particular, the efficiency of NBCA injection was due to its effect of plugging the tract and causing the embolization of adjacent small vessels. With regard to procedural handling, RF electrocauterization of the tract is superior to injection of NBCA

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. Copper oxide nanoparticles aggravate airway inflammation and mucus production in asthmatic mice via MAPK signaling.

    Science.gov (United States)

    Park, Ji-Won; Lee, In-Chul; Shin, Na-Rae; Jeon, Chan-Mi; Kwon, Ok-Kyoung; Ko, Je-Won; Kim, Jong-Choon; Oh, Sei-Ryang; Shin, In-Sik; Ahn, Kyung-Seop

    2016-05-01

    Copper oxide nanoparticles (CuONPs), metal oxide nanoparticles were used in multiple applications including wood preservation, antimicrobial textiles, catalysts for carbon monoxide oxidation and heat transfer fluid in machines. We investigated the effects of CuONPs on the respiratory system in Balb/c mice. In addition, to investigate the effects of CuONPs on asthma development, we used a murine model of ovalbumin (OVA)-induced asthma. CuONPs markedly increased airway hyper-responsiveness (AHR), inflammatory cell counts, proinflammatory cytokines and reactive oxygen species (ROS). CuONPs induced airway inflammation and mucus secretion with increases in phosphorylation of the MAPKs (Erk, JNK and p38). In the OVA-induced asthma model, CuONPs aggravated the increased AHR, inflammatory cell count, proinflammatory cytokines, ROS and immunoglobulin E induced by OVA exposure. In addition, CuONPs markedly increased inflammatory cell infiltration into the lung and mucus secretions, and MAPK phosphorylation was elevated compared to OVA-induced asthmatic mice. Taken together, CuONPs exhibited toxicity on the respiratory system, which was associated with the MAPK phosphorylation. In addition, CuONPs exposure aggravated the development of asthma. We conclude that CuONPs exposure has a potential toxicity in humans with respiratory disease. PMID:26472121

  13. 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)

  14. What Is Liver Cancer?

    Science.gov (United States)

    ... Topic Key statistics about liver cancer What is liver cancer? Cancer starts when cells in the body ... structure and function of the liver. About the liver The liver is the largest internal organ. It ...

  15. An experimental study on the effect of mixture of absolute ethanol and lipiodol injected into normal liver of rabbit : CT features and histopathologic changes

    International Nuclear Information System (INIS)

    To investigate the safety and usefulness of Lipiodol-percutaneous transhepatic ethanol injection(LPEI) and to determine the appropriate concentration of Lipiodol during L-PEI. This was achieved by evalvating CT findings and histopathologic changes according to the concentration of Lipiodol, amount of ethanol, and the time interval after injection into normal rabbit liver. This experimental study involved 18 New Zealand rabbits under US guidance. They were divided into five groups according to injected materials; two rabbits with 0.4cc of normal saline(group I), six with 0.4cc of ethanol in the left hepatic lobe(group II), and 0.4cc of Lipiodol in the right hepatic lobe(group III), five rabbits with 5% Lipiodol-ethanol(5% vol. of Lipiodol+95% vol. of ethanol), 0.2cc in the right hepatic lobe, and 0.4cc in the left(group IV); and five rabbits with 10% Lipiodol-ethanol as per group IV(group V). CT was performed immediately, one week, two weeks, and three-four weeks after injection, and pathologic specimens were obtained on the third day(acute phase) and during the third or fourth week(chronic phase) after injection. On CT, intrahepatic localization of the L-PEI injection site was well demonstrated as a focal high attenuated area which gradually decreased in attenuation on follow up CT. The opacification of the inferior vena cava by Lipiodol, the linear distribution of Lipiodol along portal veins or fissures, and peritoneal leakage were clearly demonstrated in groups III-V, though the effects gradually disappeared during follow-up CT. There was no remarkable difference in gross CT attenuation between group IV and group V. The main pathologic findings during the acute phase of group II were coagulation necrosis surrounded by macrophage, inflammatory reaction, and early periportal and subcapsular fibrosis. The findings in group IV and V were similar to those in group II and additional fat vacuole accumulations in the necrotic area were also seen. During the chronic phase

  16. 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 ...

  17. 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 ...

  18. 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 ...

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

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

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

  20. 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

  1. Changes in FGF21 Serum Concentrations and Liver mRNA Expression in an Experimental Model of Complete Lipodystrophy and Insulin-Resistant Diabetes

    Czech Academy of Sciences Publication Activity Database

    Špolcová, Andrea; Holubová, Martina; Mikulášková, Barbora; Nagelová, Veronika; Štofková, A.; Lacinová, Z.; Jurčovičová, J.; Haluzík, M.; Maletínská, Lenka; Železná, Blanka

    2014-01-01

    Roč. 63, č. 4 (2014), s. 483-490. ISSN 0862-8408 R&D Projects: GA ČR GAP303/10/1368; GA ČR GAP303/12/0576 Institutional support: RVO:61388963 Keywords : FGF21 * A-ZIP mice * lipodystrophy * insulin resistance * fatty liver * GLUT-1 Subject RIV: CE - Biochemistry Impact factor: 1.293, year: 2014

  2. [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

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

    Science.gov (United States)

    Heeba, Gehan H; Morsy, Mohamed A

    2015-11-01

    Fucoidan, a sulfated polysaccharide derived from brown seaweeds, possesses a wide range of pharmacological properties. In the present study, we investigated the therapeutic effect of fucoidan on non-alcoholic fatty liver disease (NAFLD) in rats. Rats were fed a high-fat diet (HFD) for 12 weeks to induce NAFLD. Oral administrations of fucoidan (100mg/kg, orally), metformin (200mg/kg, orally) or the vehicle were started in the last four weeks. Results showed that administration of fucoidan for 4 weeks attenuated the development of NAFLD as evidenced by the significant decrease in liver index, serum liver enzymes activities, serum total cholesterol and triglycerides, fasting serum glucose, insulin, insulin resistance, and body composition index. Further, fucoidan decreased hepatic malondialdehyde as well as nitric oxide concentrations, and concomitantly increased hepatic reduced glutathione level. In addition, the effect of fucoidan was accompanied with significant decrease in hepatic mRNA expressions of tumor necrosis factor-α, interleukins-1β and matrix metalloproteinase-2. Furthermore, histopathological examination confirmed the effect of fucoidan. In conclusion, fucoidan ameliorated the development of HFD-induced NAFLD in rats that may be, at least partly, related to its hypolipidemic, insulin sensitizing, antioxidant and anti-inflammatory mechanisms. PMID:26498267

  4. [Liver intervention].

    Science.gov (United States)

    Oi, H

    2000-12-01

    Interventional radiology is now widely performed for the treatment of liver tumors, because surgery is sometimes limited by poor liver function. Transcatheter arterial chemoembolization(TACE) is an effective therapy for hepatocellular carcinoma. Lipiodol TACE shows a strong antitumor effect because of the overflow of excess iodized oil into the portal veins, and segmental TACE is recommended to avoid deteriorating liver function. Selective CT arteriography is performed in order to decide on the treatment area, and TACE under CT guidance leads to effective results in terms of dense accumulation of the chemotherapeutic drug in the individual tumors that are affected by the ischemic state and anticancer drugs. Percutaneous microwave or radiofrequency coagulation therapy is adequate for a few of the hypovascular tumors. Excessive coagulation through the needle tract is indispensable in these therapies, and precisely designed puncture is necessary to minimize damage to the liver parenchyma. Selective chemotherapy to the tumor-bearing organ is the first step in a number of liver tumors. Continuous intra-arterial infusion chemotherapy is performed for multiple liver metastases. The reservoir implantation technique is percutaneously achieved via the left subclavian artery under ultrasound guidance, without the exposure of an artery in the incision method, which can induce thrombus formation. PMID:11197832

  5. 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.

  6. 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)....

  7. 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

  8. 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...

  9. Didymin reverses phthalate ester-associated breast cancer aggravation in the breast cancer tumor microenvironment

    Science.gov (United States)

    HSU, YA-LING; HSIEH, CHIA-JUNG; TSAI, EING-MEI; HUNG, JEN-YU; CHANG, WEI-AN; HOU, MING-FENG; KUO, PO-LIN

    2016-01-01

    The present study demonstrated two novel findings. To the best of our knowledge, it is the first study to demonstrate that regulated upon activation, normal T-cell expressed and secreted (RANTES), produced by breast tumor-associated monocyte-derived dendritic cells (TADCs) following breast cancer cell exposure to phthalate esters, may contribute to the progression of cancer via enhancement of cancer cell proliferation, migration and invasion. Furthermore, the present study revealed that didymin, a dietary flavonoid glycoside present in citrus fruits, was able to reverse phthalate ester-mediated breast cancer aggravation. MDA-MB-231 cells were treated with butyl benzyl phthalate (BBP), di-n-butyl phthalate (DBP) or di-2-ethylhexyl phthalate (DEHP). Subsequently, the conditioned medium (CM) was harvested and cultured with monocyte-derived dendritic cells (mdDCs). Cultures of MDA-MB-231 cells with the conditioned medium of BBP-, DBP- or DEHP-MDA-MB-231 tumor-associated mdDCs (BBP-, DBP- or DEHP-MDA-TADC-CM) demonstrated enhanced proliferation, migration and invasion. Exposure of the MDA-MB-231 cells to DBP induced the MDA-TADCs to produce the inflammatory cytokine RANTES, which subsequently induced MDA-MB-231 cell proliferation, migration and invasion. Depleting RANTES reversed the effects of DBP-MDA-TADC-mediated MDA-MB-231 cell proliferation, migration and invasion. In addition, didymin was observed to suppress phthalate-mediated breast cancer cell proliferation, migration and invasion. The present study suggested that didymin was capable of preventing phthalate ester-associated cancer aggravation. PMID:26893687

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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)

    AndreyVKozlov

    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.

  15. 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

    International Nuclear Information System (INIS)

    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 cm3 versus 10.64 ± 3.25 cm3 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 cm3 versus 21.48 ± 3.51 cm3 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 cm3 versus 13.44 ± 4.25 cm3; p 0.05). Conclusion: Using a new type of internally cooled RF electrode, we could induce different volumes of the RF ablation zone by means of

  16. 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

  17. 77 FR 24415 - Inflation Adjustment of the Aggravated Maximum Civil Monetary Penalty for a Violation of a...

    Science.gov (United States)

    2012-04-24

    ... $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, by... should be increased to $650. 73 FR 79698 (Dec. 30, 2008). In 2009, FRA also published a...

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

    Directory of Open Access Journals (Sweden)

    Olavi-Jüri Luik

    2015-12-01

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

  19. Late onset painful cold-aggravated myotonia: three families with SCN4A L1436P mutation.

    Science.gov (United States)

    Bissay, Véronique; Keymolen, Kathelijn; Lissens, Willy; Laureys, Guy; Schmedding, Eric; De Keyser, Jacques

    2011-08-01

    We describe three Belgian families with a L1436P mutation in the SCN4A gene, causing a sodium channel myotonia with an atypical clinical presentation, characterized by late onset painful cold-aggravated myotonia. These families represent a distinct phenotype within the spectrum of sodium channel myotonia. PMID:21664816

  20. 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.

  1. 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...

  2. 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 ...

  3. Liver transplant - series (image)

    Science.gov (United States)

    The liver is in the right upper abdomen. The liver serves many functions, including the detoxification of substances delivered ... A liver transplant may be recommended for: liver damage due to alcoholism (Alcoholic cirrhosis) primary biliary cirrhosis long-term ( ...

  4. Liver cancer - hepatocellular carcinoma

    Science.gov (United States)

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

  5. 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)

  6. 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

  7. 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

  8. 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; Bjerring, Martin; Røntved, Christine Maria

    2013-01-01

    parameters, but affected the daily milk yield and some milk parameters transiently, that is, the presence of blood in milk, increased E. coli counts and MAA levels during the acute disease stage. Combined biopsying had no effect on the parameters in the recovery stage apart from the presence of blood in the......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 cows were divided into a biopsy group (B) (n = 16) and a no-biopsy group (NB) (n = 16) and were sampled in the acute disease stage and in the recovery stage. The cows’ pre-disease period served as a control period for establishing baseline values for the investigated parameters. A total of 32...

  9. 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

  10. An experimental study on the treatment of nude mice with liver carcinoma by intratumoral injection with 188Re rhenium sulfide suspension

    International Nuclear Information System (INIS)

    Objective: To prepare a [188Re] rhenium sulfide suspension and to evaluate its therapeutic effects on liver carcinoma by intratumoral injection. Methods: 30 nude mice bearing SMMC-7721 human liver carcinoma were used for the biodistribution study after intratumoral injection of [188Re] rhenium sulfide suspension or sodium [188Re] perrhenate solution. Another 30 tumor-bearing nude mice were divided into six groups, four groups of them were treated with a 0.1 mL [188Re] rhenium sulfide suspension at doses of 3.7, 7.4, 18.5, 29.6 MBq by a single intratumoral injection. For control studies, the remaining two groups were injected with nonradioactive rhenium sulfide suspension and Hanks' balanced salt solution, respectively. Every injection was repeated 6 days later. Results: The retention percentages of radioactivity (% ID) in tumors injected with [188Re] rhenium sulfide suspension were (90.96 +- 6.63)%, (86.09 +- 22.58)% and (87.62 +- 13.97)% at 1, 24 and 48 h, respectively, which were much higher than retention in normal organs evaluated. In the case of sodium 188Re-perrhenate solution, the % ID values were only (1.66 +- 0.35)%, (0.02 +- 0.01)% and (0.01 +- 0.01)%, respectively. Tumor inhibition ratios were as high as 89% when the peripheral portion of tumor (0.5 - 0.6 cm from center) absorbed an activity share of about 507.6 Gy . Conclusion: Intratumoral injection of [188Re] rhenium sulfide suspension results in significant tumor restraint and it is indicated that this is a highly potential approach to the treatment of hepatic carcinoma

  11. 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.

  12. 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.

  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. DNase I aggravates islet β-cell apoptosis in type 2 diabetes

    Science.gov (United States)

    ZHU, BIN; ZHANG, LEI; ZHANG, YUE-YING; WANG, LEI; LI, XIN-GANG; LIU, TENG; FU, YU-KE; ZHENG, YAN-FEI; LI, PING; ZHAO, ZHI-GANG

    2016-01-01

    Deoxyribonuclease I (DNase I) is an endonuclease responsible for the destruction of chromatin during apoptosis. However, its role in diabetes remains unclear. The aim of the current study was to investigate the role of DNase I combined with high glucose levels in β-cell apoptosis. Human samples were collected and the DNase I activity was examined. High glucose-cultured INS-1 cells were transfected with DNase I small interfering RNA (siRNA) and the cell apoptosis was examined by western blotting and flow cytometry. Cell viability was analyzed by the Cell Counting Kit-8 assay. Cell apoptosis resulting from 50 mU/μl DNase I was also observed by flow cytometry, terminal deoxynucleotidyl transferase dUTP nick-end labeling stain and western blotting. Compared with healthy controls, the serum DNase I activity of patients with diabetes was significantly increased (Pdiabetes, and high glucose combined with increased DNase I is suggested to aggravate β-cell apoptosis. PMID:27082840

  15. Organic molecules showing the characteristics of localised corrosion aggravation and inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Tan Yongjun, E-mail: yj.tan@curtin.edu.a [Department of Chemistry, Curtin University, GPO Box U1987, Perth (Australia); Mocerino, Mauro; Paterson, Tristan [Department of Chemistry, Curtin University, GPO Box U1987, Perth (Australia)

    2011-05-15

    Research highlights: {yields} Novel experiment for the discovery of localised corrosion inhibitors. {yields} New method of identifying inhibitors promoting random distribution of anodic currents. {yields} Discovery of resorcinarene acid as an effective localised corrosion inhibitor. - Abstract: The behaviour of imidazoline and an acid functionalised resorcinarene as steel corrosion inhibitors in carbon dioxide (CO{sub 2})-saturated brine solutions has been studied using an electrochemically integrated multi-electrode array namely the wire beam electrode (WBE). Both imidazoline and resorcinarene acid provided excellent inhibition to general CO{sub 2} corrosion; however imidazoline was found to aggravate localised corrosion by creating a small number of major anodes that focused on a small area of the WBE surface, leading to highly concentrated anodic dissolution. The resorcinarene acid showed distinctively different behaviour by generating a large number of minor anodes randomly distributing over the WBE surface, leading to insignificant general anodic dissolution. These results indicate that resorcinarene acid provided effective localised corrosion inhibition by promoting a random distribution of insignificant anodic currents.

  16. 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

  17. 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. PMID:19236166

  18. Efficacy of enzyme replacement therapy in an aggravated mouse model of metachromatic leukodystrophy declines with age.

    Science.gov (United States)

    Matthes, Frank; Stroobants, Stijn; Gerlach, Debora; Wohlenberg, Claudia; Wessig, Carsten; Fogh, Jens; Gieselmann, Volkmar; Eckhardt, Matthias; D'Hooge, Rudi; Matzner, Ulrich

    2012-06-01

    Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by a functional deficiency of arylsulfatase A (ASA). Previous studies in ASA-knockout mice suggested enzyme replacement therapy (ERT) to be a promising treatment option. The mild phenotype of ASA-knockout mice did, however, not allow to examine therapeutic responses of the severe neurological symptoms that dominate MLD. We, therefore, generated an aggravated MLD mouse model displaying progressive demyelination and reduced nerve conduction velocity (NCV) and treated it by weekly intravenous injections of 20 mg/kg recombinant human ASA for 16 weeks. To analyze the stage-dependent therapeutic effects, ERT was initiated in a presymptomatic, early and progressed disease stage, at age 4, 8 and 12 months, respectively. Brain sulfatide storage, NCV and behavioral alterations were improved only in early, but not in late, treated mice showing a clear age-dependent efficacy of treatment. Hematopoietic stem cell transplantation (HSCT) for late-onset variants is the only therapeutic option for MLD to date. ERT resembles a part of the HSCT rationale, which is based on ASA supply by donor cells. Beyond ERT, our results, therefore, corroborate the clinical observation that HSCT is only effective when performed in early stages of disease. PMID:22388935

  19. 147 Mitigating and Aggravating Circumstances. Their Impact on Judicial Individualization of Punishment

    Directory of Open Access Journals (Sweden)

    Cosmin Peonaşu

    2015-08-01

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

  20. 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)

  1. IL-1 Receptor Antagonist Treatment Aggravates Staphylococcal Septic Arthritis and Sepsis in Mice.

    Directory of Open Access Journals (Sweden)

    Abukar Ali

    Full Text Available Interleukin-1 receptor antagonist (IL-1Ra is the primary therapy against autoinflammatory syndromes with robust efficacy in reducing systemic inflammation and associated organ injury. However, patients receiving IL-1Ra might be at increased risk of acquiring serious infections.To study whether IL-1Ra treatment deteriorates Staphylococcus aureus (S. aureus septic arthritis and sepsis in mice.NMRI mice were treated with anakinra (IL-1Ra daily for 7 days before intravenous inoculation with S. aureus strain Newman in both arthritogenic and lethal doses. The clinical course of septic arthritis, histopathological and radiological changes of the joints, as well as the mortality were compared between IL-1Ra treated and control groups.IL-1Ra treated mice developed more frequent and severe clinical septic arthritis. Also, the frequency of polyarthritis was significantly higher in the mice receiving IL-1Ra therapy. In line with the data from clinical arthritis, both histological and radiological signs of septic arthritis were more pronounced in IL-1Ra treated group compared to controls. Importantly, the mortality of IL-1Ra treated mice was significantly higher than PBS treated controls.IL-1Ra treatment significantly aggravated S. aureus induced septic arthritis and increased the mortality in these mice.

  2. 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.

  3. 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

  4. 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

  5. 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...

  6. Uptake of aluminium ion by the liver

    International Nuclear Information System (INIS)

    The specific uptake by the rat liver of 28Al was shown. There was specific uptake of 28Al by liver cell nuclei and DNA. This uptake was blocked by prior treatment with stable aluminium. It is concluded that aluminium enters the liver cell by some specific mechanism and that the reaction of aluminium with DNA inside the hepatocyte nucleus could be a mechanism responsible for the development of aluminium-induced experimental porphyria in the rat

  7. Antioxidants in liver health

    OpenAIRE

    Casas-Grajales, Sael; Muriel, Pablo

    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 leads to deleterious processes in the liver and produces liver diseases. T...

  8. 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

  9. 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)

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

    Science.gov (United States)

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

    2016-01-15

    Lambs infected with the Cullompton isolate of Fasciola hepatica were treated orally or subcutaneously with 10mg/kg of closantel at 16 weeks post-infection. Adult flukes were recovered from the liver of individual animals at 12h, 24h, or 36h post-treatment. The flukes were processed for histological analysis. In general, degenerative changes in the reproductive and somatic tissues were progressive, and were most marked in flukes exposed to closantel in vivo for 36h. However, flukes from a 12h subcutaneously-treated lamb showed marked deterioration of the testis, possibly because a portion of the dose has been delivered intravenously. Fewer intact eggs were seen in the uterus of flukes exposed to closantel for longer times (whether administered subcutaneously or orally to the host). The most conspicuous closantel-induced effect in flukes from treated hosts was progressive damage to the tegumental syncytium. While the flukes from 24h-treated hosts showed relatively minor damage to limited areas of the syncytium, towards the posterior end, the flukes from 36h-treated hosts (and flukes from the lamb that putatively received intravenous dosage) had lost large areas of the surface syncytium from the posterior end and dorsal surface, although the syncytium over the anterior end and the anterior ventral surface was largely spared. In areas where the syncytium had sloughed, the underlying structures such as the vitelline follicles, gut profiles and testis profiles, showed marked degeneration and breakdown. Other changes included cell depletion and early stage apoptosis in the testis, ovary and vitelline follicles. This study establishes a model for histological changes in closantel-sensitive F. hepatica exposed to closantel in vivo. Histopathological studies could be complementary to the efficacy controlled test for for closantel resistance in fluke populations. PMID:26790736

  11. 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.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    Miyauchi Akira

    2011-08-01

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

  14. 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.

  15. 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

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    Rogério Saad Hossne

    2002-08-01

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

  18. Chronic unpredictable mild stress combined with a high-fat diets aggravates atherosclerosis in rats

    OpenAIRE

    Wang, Shuling; Xiaoling, Gao; Pingting, Li; Shuqiang, Liu; Yuaner, Zeng

    2014-01-01

    Background Depression and high-fat diet are both known as independent risk factors for atherosclerosis and other cardiovascular diseases, suggesting the interaction of psychological and physiological factors in the development of these diseases. The liver is a crucial organ that facilitate lipid metabolism especially in reverse cholesterol transport (RCT), while according to the theory of Traditional Chinese Medicine, depression as a kind of psychological stress has an influence on hepatic fu...

  19. Deficiency of Glycine N-Methyltransferase Aggravates Atherosclerosis in Apolipoprotein E–Null Mice

    OpenAIRE

    Chen, Chien-Yu; Ching, Li-Chieh; Liao, Yi-Jen; Yu, Yuan-Bin; Tsou, Chia-Yuan; Shyue, Song-Kun; Chen, Yi-Ming Arthur; Lee, Tzong-Shyuan

    2012-01-01

    The mechanism underlying the dysregulation of cholesterol metabolism and inflammation in atherogenesis is not understood fully. Glycine N-methyltransferase (GNMT) has been implicated in hepatic lipid metabolism and the pathogenesis of liver diseases. However, little is known about the significance of GNMT in atherosclerosis. We showed the predominant expression of GNMT in foamy macrophages of mouse atherosclerotic aortas. Genetic deletion of GNMT exacerbated the hyperlipidemia, inflammation a...

  20. MEDICINAL PLANTS AGAINST LIVER DISEASES

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    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.

  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. Estrogen aggravates inflammation in Pseudomonas aeruginosa pneumonia in cystic fibrosis mice

    Directory of Open Access Journals (Sweden)

    Gagnon Stéphane

    2010-11-01

    Full Text Available Abstract Background Among patients with cystic fibrosis (CF, females have worse pulmonary function and survival than males, primarily due to chronic lung inflammation and infection with Pseudomonas aeruginosa (P. aeruginosa. A role for gender hormones in the causation of the CF "gender gap" has been proposed. The female gender hormone 17β-estradiol (E2 plays a complex immunomodulatory role in humans and in animal models of disease, suppressing inflammation in some situations while enhancing it in others. Helper T-cells were long thought to belong exclusively to either T helper type 1 (Th1 or type 2 (Th2 lineages. However, a distinct lineage named Th17 is now recognized that is induced by interleukin (IL-23 to produce IL-17 and other pro-inflammatory Th17 effector molecules. Recent evidence suggests a central role for the IL-23/IL-17 pathway in the pathogenesis of CF lung inflammation. We used a mouse model to test the hypothesis that E2 aggravates the CF lung inflammation that occurs in response to airway infection with P. aeruginosa by a Th17-mediated mechanism. Results Exogenous E2 caused adult male CF mice with pneumonia due to a mucoid CF clinical isolate, the P. aeruginosa strain PA508 (PA508, to develop more severe manifestations of inflammation in both lung tissue and in bronchial alveolar lavage (BAL fluid, with increased total white blood cell counts and differential and absolute cell counts of polymorphonuclear leukocytes (neutrophils. Inflammatory infiltrates and mucin production were increased on histology. Increased lung tissue mRNA levels for IL-23 and IL-17 were accompanied by elevated protein levels of Th17-associated pro-inflammatory mediators in BAL fluid. The burden of PA508 bacteria was increased in lung tissue homogenate and in BAL fluid, and there was a virtual elimination in lung tissue of mRNA for lactoferrin, an antimicrobial peptide active against P. aeruginosa in vitro. Conclusions Our data show that E2 increases the

  3. 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).

  4. 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

  5. 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-

  6. Amebic liver abscess

    Science.gov (United States)

    ... liver in response to an intestinal parasite called Entamoeba histolytica . Causes Amebic liver abscess is caused by Entamoeba histolytica. This parasite causes amebiasis , an intestinal infection that ...

  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. 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

  9. Improved donor liver position selection and revascularization for heterotopic auxiliary liver transplantation with portal vein arterialization

    OpenAIRE

    Li, Jun; Zhang, Yujun; Ren, Jianjun; Zhang, Junjing; Qiao, Jianliang; MENG, XINGKAI

    2015-01-01

    Purpose: To establish an animal model of improved donor liver position selection and revascularization for heterotopic auxiliary liver transplantation with portal vein arterialization (HALT-PVA). Methods: Sprague-Dawley rats were utilized to establish models. Improved HALT-PVA was conducted for the experimental rat: hepatic common artery of donor liver was end-to-side anastomosed to portal vein which was end-to-side anastomosed to the left common iliac artery of host rat, while the segments o...

  10. 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.

  11. 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.

  12. 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

  13. 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 ...

  14. 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 ...

  15. 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

  16. Liver Function Tests

    Science.gov (United States)

    ... a Healthy Liver In the Field Call to Action - Change Tomorrow, Give Today Liver Lowdown Sept 2013 Recovery Month Path to Wellness ... Patient Story-Lynette In the Field Call to Action 5 Things About Hep Healthy Summer Tips Liver Lowdown June 2013 Liver Lowdown July/Aug 2014 ...

  17. 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. ...

  18. 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...

  19. 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.

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

    Institute of Scientific and Technical Information of China (English)

    Tie-long Zheng; Ping-an Wang; Dian-li Wang; Cheng-fu Sun; Yuan Hong; Qi Wang; Jun Cheng

    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. 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

  2. Cold-aggravated pain in humans caused by a hyperactive NaV1.9 channel mutant.

    Science.gov (United States)

    Leipold, Enrico; Hanson-Kahn, Andrea; Frick, Miya; Gong, Ping; Bernstein, Jonathan A; Voigt, Martin; Katona, Istvan; Oliver Goral, R; Altmüller, Janine; Nürnberg, Peter; Weis, Joachim; Hübner, Christian A; Heinemann, Stefan H; Kurth, Ingo

    2015-01-01

    Gain-of-function mutations in the human SCN11A-encoded voltage-gated Na(+) channel NaV1.9 cause severe pain disorders ranging from neuropathic pain to congenital pain insensitivity. However, the entire spectrum of the NaV1.9 diseases has yet to be defined. Applying whole-exome sequencing we here identify a missense change (p.V1184A) in NaV1.9, which leads to cold-aggravated peripheral pain in humans. Electrophysiological analysis reveals that p.V1184A shifts the voltage dependence of channel opening to hyperpolarized potentials thereby conferring gain-of-function characteristics to NaV1.9. Mutated channels diminish the resting membrane potential of mouse primary sensory neurons and cause cold-resistant hyperexcitability of nociceptors, suggesting a mechanistic basis for the temperature dependence of the pain phenotype. On the basis of direct comparison of the mutations linked to either cold-aggravated pain or pain insensitivity, we propose a model in which the physiological consequence of a mutation, that is, augmented versus absent pain, is critically dependent on the type of NaV1.9 hyperactivity. PMID:26645915

  3. 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)

  4. 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

  5. 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

  6. 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.

  7. 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

  8. Liver and water metabolism

    International Nuclear Information System (INIS)

    The causes for the disturbance of hydro-electrolytic equilibrium observed in cirrhosis patients are far from clear. Studies on the static distribution of liquid in the organism and also on anomalies in the distribution of deuterium oxide and tritiated water provide no direct explanation of the nature of the water retaining mechanism. At the period when the illness is established, endocrine factors and electrolytic perturbations contribute to maintaining or increasing oliguresis, but they cannot be held solely responsible in the initial stages of evolution. An explanation of the ascites should therefore be looked for in a non-functioning of the polygonal or Kupffer cells. The hypothesis of an insufficient rejection of water outside the lymph spaces of the liver during cirrhosis is put forward, but the experimental demonstration of such a phenomenon proves very difficult. (author)

  9. 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

  10. 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.

  11. 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.

  12. 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...

  13. 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.

  14. Therapeutic hypothermia for acute liver failure

    DEFF Research Database (Denmark)

    Stravitz, R.T.; Larsen, Finn Stolze

    2009-01-01

    transplantation or spontaneous liver regeneration follows in short order. To buy time, the induction of therapeutic hypothermia (core temperature 32 degrees C-35 degrees C) has been shown to effectively bridge patients to transplant. Similar to the experience in patients with cerebral edema after other neurologic...... of liver injury. Hypothermia has not been adequately studied for its safety and theoretically may increase the risk of infection, cardiac dysrhythmias, and bleeding, all complications independently associated with acute liver failure. Therefore, although an ample body of experimental and human data...

  15. 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. PMID:26447960

  16. Orthotopic Liver Transplantation: Is There a Risk for Listeria monocytogenes Infection?

    Directory of Open Access Journals (Sweden)

    Urs Ehehalt

    2010-01-01

    Full Text Available Immunosuppression of any kind is a known risk factor for infection with Listeria monocytogenes (L. monocytogenes. Particularly, patients with impaired liver function are at increased risk of developing an aggravated course of infection with this bacterial pathogen (see Nolla-Salas et al.; 2002 and Cabellos et al.; 2008. It is a well-known pathogen in immunocompromised patients, but has only seldom been reported following orthotopic liver transplantation. Invasion of the central nervous system presenting as meningitis or meningoencephalitis and bacteremia are the principal clinical manifestations of listerial infections (see Brouwer et al.; 2006. We present an account of a case of a patient who developed L. monocytogenes meningitis during the early period after liver transplantation.

  17. 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)

  18. 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.)

  19. 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.

  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. Autoimmune liver disease panel

    Science.gov (United States)

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

  3. 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 ...

  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 be ...

  5. 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 ...

  6. 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...... from 1992 to 2005. MATERIAL AND METHODS: A retrospective study of the journals of 440 patients, who underwent 506 LTXs between 1992 and 2005, showed that 14 patients underwent LTX for PLD. All patients had normal liver function. Three were receiving haemodialysis and thus underwent combined liver...

  7. 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

  8. 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...

  9. 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 ...

  10. 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 ( ...

  11. 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

  12. 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.

  13. 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-

  14. 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.

  15. 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.

  16. 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.

  17. Cell Therapies for Liver Diseases

    OpenAIRE

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

    2012-01-01

    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...

  18. 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

  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. 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

  1. Hromonal regulation of sex differentiated liver carcinogenesis in the rat

    OpenAIRE

    Liao, Dezhong

    1996-01-01

    Endocrine factors influence cancer development in a variety of reproductive and non-reproductive tissues and organs. The incidence of liver cancer is higher in men than in women and long temm administration of androgens and estrogens has been reported to increase the risk for liver cancer formation, supporting the importance of hormonal factors in the etiology of this tumor. Hormonal effects on liver carcinogenesis have been demonstrated also in experimental animals. In the resistant hepatocy...

  2. 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.

  3. 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

  4. 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

  5. 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

  6. Alcoholic liver disease: Treatment

    OpenAIRE

    Suk, Ki Tae; Kim, Moon Young; Baik, Soon Koo

    2014-01-01

    The excess consumption of alcohol is associated with alcoholic liver diseases (ALD). ALD is a major healthcare problem, personal and social burden, and significant reason for economic loss worldwide. The ALD spectrum includes alcoholic fatty liver, alcoholic hepatitis, cirrhosis, and the development of hepatocellular carcinoma. The diagnosis of ALD is based on a combination of clinical features, including a history of significant alcohol intake, evidence of liver disease, and laboratory findi...

  7. 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.

  8. 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. PMID:27037020

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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 ...

  17. Liver Disease and Adult Vaccination

    Science.gov (United States)

    ... and click "GO" or visit Healthmap Vaccine Finder . Liver Disease and Adult Vaccination Recommend on Facebook Tweet ... critical for people with health conditions such as liver disease. If you have chronic liver disease, talk ...

  18. 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 ...

  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 (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) ...

  1. 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

  2. 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 ...

  3. Liver transplant - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100090.htm Liver transplant - series To use the sharing features on this ... A.M. Editorial team. Related MedlinePlus Health Topics Liver Transplantation A.D.A.M., Inc. is accredited by ...

  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. Stem Cell Therapies for Treatment of Liver Disease

    Directory of Open Access Journals (Sweden)

    Clara Nicolas

    2016-01-01

    Full Text Available Cell therapy is an emerging form of treatment for several liver diseases, but is limited by the availability of donor livers. Stem cells hold promise as an alternative to the use of primary hepatocytes. We performed an exhaustive review of the literature, with a focus on the latest studies involving the use of stem cells for the treatment of liver disease. Stem cells can be harvested from a number of sources, or can be generated from somatic cells to create induced pluripotent stem cells (iPSCs. Different cell lines have been used experimentally to support liver function and treat inherited metabolic disorders, acute liver failure, cirrhosis, liver cancer, and small-for-size liver transplantations. Cell-based therapeutics may involve gene therapy, cell transplantation, bioartificial liver devices, or bioengineered organs. Research in this field is still very active. Stem cell therapy may, in the future, be used as a bridge to either liver transplantation or endogenous liver regeneration, but efficient differentiation and production protocols must be developed and safety must be demonstrated before it can be applied to clinical practice.

  6. 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.

  7. 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

  8. 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.

  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....

  10. 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.

  11. 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…

  12. 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...

  13. Liver atrophy following portacaval shunt in normal rats: A morphologic and ultrastructural study

    OpenAIRE

    Radosavljević Tatjana; Todorović Vera N.; Boričić Ivan V.; Šikić Branka

    2003-01-01

    The aim of the current study was to examine morphological and ultrastructural changes in the rat liver in an experimental model of chronic liver disease (end-to-side portacaval shunt). The surgical procedure providing an end-to-side portacaval shunt (PCS) was performed in Wistar rats. The liver and pancreas weights were determined 8 weeks after the operation, when liver histology and ultrastructural patterns of hepatocytes were examined. Body weights were not significantly different between t...

  14. Hepatic regeneration after sublethal partial liver irradiation in cirrhotic rats

    International Nuclear Information System (INIS)

    Our previous animal study had demonstrated that partial liver irradiation (IR) could stimulate regeneration in the protected liver, which supported the measurements adopted in radiotherapy planning for hepatocellular carcinoma. The purpose of this present study is to investigate whether cirrhotic liver repopulation could be triggered by partial liver IR. The cirrhosis was induced by thioacetamide (TAA) in rats. After cirrhosis establishment, TAA was withdrawn. In Experiment 1, only right-half liver was irradiated with single doses of 5 Gy, 10 Gy and 15 Gy, respectively. In Experiment 2, right-half liver was irradiated to 15 Gy, and the left-half to 2.5 Gy, 5 Gy and 7.5 Gy, respectively. The regeneration endpoints, including liver index (LI); mitotic index (MI); liver proliferation index (LPI); proliferating cell nuclear antigen-labeling index (PCNA-LI); serum hepatic growth factor (HGF), vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-α and interleukin (IL)-6, were evaluated on 0 day, 30-day, 60-day, 90-day, 120-day and 150-day after IR. Serum and in situ TGF-β1 were also measured. In both experimental groups, the IR injuries were sublethal, inducing no more than 9% animal deaths. Upon TAA withdrawal, hepatic regeneration decelerated in the controls. In Experiment 1 except for LI, all other regeneration parameters were significantly higher than those in controls for both right-half and left-half livers. In Experiment 2 all regeneration parameters were also higher compared with those in controls for both half livers. Serum HGF and VEGF were increased compared with that of controls. Both unirradiated and low dose-irradiated cirrhotic liver were able to regenerate triggered by sublethal partial liver IR and higher doses and IR to both halves liver triggered a more enhanced regeneration. (author)

  15. 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

  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. Endowascular surgery of liver

    International Nuclear Information System (INIS)

    The well-known variants and above all new valid methods of endovascular surgery in treating chronic hepatitis, cirrhosis and liver tumors are described. The results of the observation of patients in the surgical clinic of the Central Research Institute of Roentgenology and Radiology which has the greatest in the USSR experience in the field of endovascular surgery of the liver are summarized. Special attention is given to the role and positive results of a catheter technique in the treatment of advanced stages of the disease as well as extensive liver resection and its conservation for trasplantation

  18. [Cysts of the liver

    DEFF Research Database (Denmark)

    Hillingso, J.G.; Kirkegaard, P.

    2008-01-01

    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......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...

  19. 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.

  20. 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 (...

  1. 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 ...

  2. 25 Ways to Love Your Liver

    Science.gov (United States)

    ... run events. Please support us. Donate | Volunteer For Liver Health Information Call 1-800-GO-LIVER (1- ... Love Your Liver 25 Ways to Love Your Liver The American Liver Foundation has put together this ...

  3. The Effect of Bisphenol A on Liver Tissue Structure and Liver Enzymes

    Directory of Open Access Journals (Sweden)

    Ozra Rahimi

    2016-03-01

    Full Text Available Background and Objectives: Bisphenol A (BPA is one of the chemical materials, which is used as monomer of epoxy resins and polycarbonate plastics. The present study was performed with the purpose of determining the effect of A on liver enzymes level and liver tissue structure. Methods: In this experimental study 40 male rats were divided into 4 groups of 10 each: The control group received olive oil at a dose of 1μg/kg bw; group II received BPA at 10μg/kg bw; group III received BPA at 50μg/kg bw; and group IV received BPA at 100μg/kg bw. The groups were administered BPA intraperitoneally for 15 days. At the end, the rats were anesthetized and after extraction of serum, their liver were removed for examination of liver enzymes and evaluated by light microscopy after H&E staining. Results: The doses of 10 and 50μg/kg bw of BPA had no significant effect on ALT enzyme and 10μg/kg bw had no significant effect on AST enzyme (p>0.05, while BPA at dose of 100 and doses 50 and 100μg/kg bw had significant effects on ALT and AST, respectively, and increased their serum concentration. BPA only at dose of 100μg/kg bw caused inflammation and vacuolization in liver tissue, and its low concentrations had no significant effect on the liver tissue. Conclusion: The results indicated that low concentrations of BPA had no significant effect on liver tissue and enzymes, but its increased concentration can cause damage to liver tissue and increase the serum levels of liver enzymes.

  4. 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.

  5. 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)

  6. 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...

  7. Nonalcoholic fatty liver disease

    DEFF Research Database (Denmark)

    Patrick-Melin, A J; Kalinski, M I; Kelly, K R;

    2009-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a rapidly emerging chronic liver disease and is reported to affect up to 70-80% of overweight and obese individuals. NAFLD represents a spectrum of liver diseases that range from simple hepatic steatosis, to a more severe and treatment resistant stage...... that features steatosis plus inflammation, termed nonalcoholic steatohepatitis (NASH), which may in turn progress to hepatic fibrosis, cirrhosis, and sub-acute liver failure. Thus, NAFLD and its subsequent complications create a significant health burden, and currently there is no effective treatment strategy...... the potential role of exercise in treating and preventing NAFLD. Regular exercise can reverse insulin resistance, suppress low-grade systemic inflammation, and attenuate inflammatory markers associated with NAFLD. Thus, exercise has the potential to become an effective treatment and prevention modality...

  8. Hepatic (Liver) Function Panel

    Science.gov (United States)

    ... help diagnose viral infections (such as hepatitis or mononucleosis) or to monitor medications that can cause liver- ... For Kids For Parents MORE ON THIS TOPIC Mononucleosis Hepatitis Blood Test: Alanine Aminotransferase (ALT, or SGPT) ...

  9. 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.

  10. 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.

  11. 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.

  12. 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 ...

  13. Research Areas: Liver Disease

    Science.gov (United States)

    ... 900 drugs and supplements.​​ Recent discoveries from NIDDK research include: Allergy drug inhibits hepatitis C in mice ... Liver Regeneration Breakthrough Using Mature Human Cells Support Research NIDDK invests in basic, clinical and translational research ...

  14. American Liver Foundation

    Science.gov (United States)

    ... Media Helpful Links Register Today To Be An Organ Donor At ORGANIZE! ORGANIZE is a non-profit that ... kin. Click here to register to be an organ donor! Run Disney With Us! Join the Liver Life ...

  15. 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)

  16. 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....

  17. 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...

  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. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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...

  5. Mice with humanized liver endothelium

    OpenAIRE

    Oude Elferink, R.P.J.; Seppen, J.; Filali, el, E.

    2014-01-01

    The only curative treatment option for a large proportion of patients suffering from a liver disorder is liver transplantation. The use of ex vivo genetically modified autologous liver cells instead of whole liver transplantation could overcome the problem of donor scarcity. Even though clinical trials have shown that transplantation of liver cells is feasible, long-term outcome is disappointing due to poor translation of animal studies to humans amongst others. In the present thesis, we soug...

  6. Autoimmune liver disease, autoimmunity and liver transplantation.

    Science.gov (United States)

    Carbone, Marco; Neuberger, James M

    2014-01-01

    Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) represent the three major autoimmune liver diseases (AILD). PBC, PSC, and AIH are all complex disorders in that they result from the effects of multiple genes in combination with as yet unidentified environmental factors. Recent genome-wide association studies have identified numerous risk loci for PBC and PSC that host genes involved in innate or acquired immune responses. These loci may provide a clue as to the immune-based pathogenesis of AILD. Moreover, many significant risk loci for PBC and PSC are also risk loci for other autoimmune disorders, such type I diabetes, multiple sclerosis and rheumatoid arthritis, suggesting a shared genetic basis and possibly similar molecular pathways for diverse autoimmune conditions. There is no curative treatment for all three disorders, and a significant number of patients eventually progress to end-stage liver disease requiring liver transplantation (LT). LT in this context has a favourable overall outcome with current patient and graft survival exceeding 80% at 5years. Indications are as for other chronic liver disease although recent data suggest that while lethargy improves after transplantation, the effect is modest and variable so lethargy alone is not an indication. In contrast, pruritus rapidly responds. Cholangiocarcinoma, except under rigorous selection criteria, excludes LT because of the high risk of recurrence. All three conditions may recur after transplantation and are associated with a greater risk of both acute cellular and chronic ductopenic rejection. It is possible that a crosstalk between alloimmune and autoimmune response perpetuate each other. An immunological response toward self- or allo-antigens is well recognised after LT in patients transplanted for non-autoimmune indications and sometimes termed "de novo autoimmune hepatitis". Whether this is part of the spectrum of rejection or an autoimmune

  7. Gut microbiota and host metabolism in liver cirrhosis.

    Science.gov (United States)

    Usami, Makoto; Miyoshi, Makoto; Yamashita, Hayato

    2015-11-01

    The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulating the activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probiotics-treated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics

  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. Th2-Associated Alternative Kupffer Cell Activation Promotes Liver Fibrosis without Inducing Local Inflammation

    Directory of Open Access Journals (Sweden)

    Giuliana López-Navarrete, Espiridión Ramos-Martínez, Karina Suárez-Álvarez, Jesús Aguirre-García, Yadira Ledezma-Soto, Sonia León-Cabrera, Marco Gudiño-Zayas, Carolina Guzmán, Gabriela Gutiérrez-Reyes

    2011-01-01

    Full Text Available Cirrhosis is the final outcome of liver fibrosis. Kupffer cell-mediated hepatic inflammation is considered to aggravate liver injury and fibrosis. Alternatively-activated macrophages are able to control chronic inflammatory events and trigger wound healing processes. Nevertheless, the role of alternative Kupffer cell activation in liver harm is largely unclear. Thus, we evaluated the participation of alternatively-activated Kupffer cells during liver inflammation and fibrosis in the murine model of carbon tetrachloride-induced hepatic damage. To stimulate alternative activation in Kupffer cells, 20 Taenia crassiceps (Tc larvae were inoculated into BALBc/AnN female mice. Six weeks post-inoculation, carbon tetrachloride or olive oil were orally administered to Tc-inoculated and non-inoculated mice twice per week during other six weeks. The initial exposure of animals to T. crassiceps resulted in high serum concentrations of IL-4 accompanied by a significant increase in the hepatic mRNA levels of Ym-1, with no alteration in iNOS expression. In response to carbon tetrachloride, recruitment of inflammatory cell populations into the hepatic parenchyma was 5-fold higher in non-inoculated animals than Tc-inoculated mice. In contrast, carbon tetrachloride-induced liver fibrosis was significantly less in non-inoculated animals than in the Tc-inoculated group. The latter showed elevated IL-4 serum levels and low IFN-γ concentrations during the whole experiment, associated with hepatic expression of IL-4, TGF-β, desmin and α-sma, as well as increased mRNA levels of Arg-1, Ym-1, FIZZ-1 and MMR in Kupffer cells. These results suggest that alternative Kupffer cell activation is favored in a Th2 microenvironment, whereby such liver resident macrophages could exhibit a dichotomic role during chronic hepatic damage, being involved in attenuation of the inflammatory response but at the same time exacerbation of liver fibrosis.

  10. 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 ...

  11. Histological and Morphometrical Studies in Liver Regeneration in Mice

    Directory of Open Access Journals (Sweden)

    Roxana Popescu

    2012-10-01

    Full Text Available Liver regeneration after loss of important cell population is a complex process involving all mature liver cell types.We study the response of hepatocytes in 24h and 48h after partial hepatectomy by microscopic and morphometricanalysis. Thirty adult male NMRI, 8 week old mice were used in the study. Liver regeneration after partialhepatectomy (68% in mice is a complex process that is performed on account differentiated mature hepatocyteproliferation, as evidenced by the presence of nuclei hypertrophy, binucleate cells or polyploidy, and numerousmitotic figures. Morphometrical analysis of cell size showed increases in average dimension of the control comparedto the experimental groups. After this study, we can conclude that liver regeneration after partial hepatectomy ismarked by the proliferation of liver cell population, while reducing the apoptotic process.

  12. Imaging in pediatric liver transplantation.

    Science.gov (United States)

    Monti, L; Soglia, G; Tomà, P

    2016-05-01

    Liver transplantation has become an established curative treatment in adult patients with acute or chronic end-stage liver diseases. In pediatric cases the number of cadaveric donor livers is not sufficient and to overcome the shortage of appropriate-sized whole liver grafts, technical variants of liver transplantation have been practiced. Reduced-size cadaveric and split cadaveric allografts have become an important therapeutic option, expanding the availability of size-appropriate organs for pediatric recipients with terminal liver disease. The number of pediatric deaths awaiting liver transplantation has been reduced by the introduction of living-related liver transplantation, developed to overcome the shortage of suitable grafts for children. It is important for radiologists to know that children have distinct imaging of liver transplantation that distinguish them from adults. A multidisciplinary pediatric liver transplantation team should be skilled in pediatric conditions and in associated processes, risks and complications. Radiologists should know the common pediatric liver diseases that lead to liver transplantation, the anastomotic techniques and the expected postoperative imaging findings. The aim of this study is to illustrate the role of non-invasive imaging such us ultrasonography, color Doppler ultrasonography, multidetector computed tomography and magnetic resonance imaging in the evaluation of pediatric liver transplantation and in potential liver donors. PMID:26909515

  13. 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

  14. 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.

  15. 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

  16. 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 < 1,5 and platelet count > 60 billion /l). Beyond these limits, the risk is higher, but still uncertain. The Danish guidelines require INR > 1.5, platelet count < 40 billion /l...... and normal APTT. In some instances the risk of not knowing the histology is so high that a biopsy is considered even with a more disturbed coagulation. Vitamin K, freshly frozen plasma and recombinant activated factor VII may reduce the risk of bleeding in specific situations, but no firm...

  17. Enhanced formation of secondary air pollutants and aggravation of urban smog due to crop residue burning emissions in North India

    Science.gov (United States)

    Sarkar, Chinmoy; Kumar, Vinod; Sinha, Vinayak

    2013-04-01

    Biomass burning causes intense perturbations to regional atmospheric chemistry and air quality and is a significant global source of reactive pollutants to the atmosphere (Andreae and Merlet, 2001). In November 2012, large areas in North India including New Delhi experienced several weeks of aggravated smog and poor air quality due to the impact of crop residue burning, which is a biannual post harvest activity that occurs during Oct-Nov and April-May every year in the agricultural belts of North western India. In-situ high temporal resolution (1 measurement every minute) measurements of a suite of volatile organic compounds measured using proton transfer reaction mass spectrometry (PTR-MS) such as acetonitrile (biomass burning tracer) and aromatic hydrocarbons were performed simultaneously with carbon monoxide, nitrogen oxides, ozone and aerosol mass concentrations (PM 2.5 and PM 10) at a suburban site (30.667°N, 76.729°E and 310 m asl), impacted by air masses that had passed over the burning fields less than 72 hours ago. By using data from the same season but before the post harvest crop residue burning activity had commenced, we were able to quantify enhancements in ambient levels of the measured species due to the crop residue burning activity. When air masses influenced by the fire emissions reached the measurement site, peak values of about 8 ppbV acetonitrile, 4 ppmV CO, 100 ppbV NOx , 30 ppbV toluene and 15 ppbV benzene were observed which represented a factor of 2-5 increase over their ambient levels in the non-fire influenced period. Emission ratios of aromatic hydrocarbons/CO also showed a marked increase. Non fire event (N.F. E.) influenced and fire event (F.E.) influenced air masses had the following emission ratio enhancements: benzene/CO (N.F.E = 3; F.E. = 5), toluene/CO (N.F.E = 4; F.E. = 8.7) and sum of C8 aromatics/CO (N.F.E = 4; F.E. = 7.3) and sum of C9 aromatics/CO (N.F.E = 2.6; F.E. = 3.4). The OH reactivity of air masses which has strong

  18. 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

  19. 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.

  20. 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

  1. 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...

  2. Neoplasms of the liver

    International Nuclear Information System (INIS)

    Primary Liver Cancer is perhaps the most prevalent malignancy in the world, particularly in South East Asia and Africa. After the discovery of hepatitis B virus as a cause of chronic liver disease often terminating cirrhosis and hepatocellular carcinoma, and, more recently, the integration of viral DNA into host chromosomal DNA, the progress made in this field has been remarkable. This book contains 35 chapters and covers all topical aspects, such as oncogenes, epidemiology, carcinogenic role of hepatitis viruses, histopathology, new imaging techniques and new treatment modalities that include ultrasound-guided intratumor injections of ethanol and targeting chemotherapy

  3. 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...... transplantation (ELT) is an established treatment option. These improvements in care are such that the majority of patients may now be expected to survive (Fig. 1). Key features of the condition have changed dramatically over time, with a remarkable fall in the incidence of cerebral edema and intracranial...

  4. 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

  5. Long-term pathological and immunohistochemical features in the liver after intraoperative whole-liver irradiation in rats

    International Nuclear Information System (INIS)

    Radiation therapy (RT) has become particularly important recently for treatment of liver tumors, but there are few experimental investigations pertaining to radiation-induced liver injuries over long-term follow-up periods. Thus, the present study examined pathological liver features over a 10-month period using an intraoperative whole-liver irradiation model. Liver function tests were performed in blood samples, whereas cell death, cell proliferation, and fibrotic changes were evaluated pathologically in liver tissues, which were collected from irradiated rats 24 h, 1, 2, 4 and 40 weeks following administration of single irradiation doses of 0 (control), 15 or 30 Gy. The impaired liver function, increased hepatocyte number, and decreased apoptotic cell proportion observed in the 15 Gy group, but not the 30 Gy group, returned to control group levels after 40 weeks; however, the Ki-67 indexes in the 15 Gy group were still higher than those in the control group after 40 weeks. Azan staining showed a fibrotic pattern in the irradiated liver in the 30 Gy group only, but the expression levels of alpha smooth muscle actin (α-SMA) and transforming growth factor-beta 1 (TGF-β1) in both the 15 and 30 Gy groups were significantly higher than those in the control group (P < 0.05). There were differences in the pathological features of the irradiated livers between the 15 Gy and 30 Gy groups, but TGF-β1 and α-SMA expression patterns supported the gradual progression of radiation-induced liver fibrosis in both groups. These findings will be useful in the future development of protective drugs for radiation-induced liver injury. (author)

  6. 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....

  7. 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" ...

  8. Modulation of the Colonic Bacterial Flora Affects Differently Bacterial Translocation and Liver Injury in an Acute Liver Injury Model

    OpenAIRE

    Adawi, Diya; Molin, Göran; Ahrné, Siv; Jeppsson, Bengt

    2011-01-01

    Objective: To evaluate the effects of the administration of different bacterial strains on the extent of liver injury and bacterial translocation in an acute liver injury model. Design: Experimental study. Setting: University hospital, Sweden. Subjects: Sprague–Dawley rats. Interventions: Six different bacterial strains (Bacteroides fragilis ATCC 25285T, Enterococcus faecium No.1, Enterococcus faecium No.2, Escherichia coli F131, Lactobacillus plantarum DSM 6595, and Bifidobacterium lon...

  9. 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

  10. 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-

  11. Cystoadenocarcinoma of the liver

    International Nuclear Information System (INIS)

    One case of an old woman is related, wuth a tumor in the right side of abdomen. The patient was submitted to ultrasography computerized tomography, demostrating hepatic and renal cystrand areas of wild mass in the liver. Adenocarcinoma was demostrated by anotmopathologic examination. (author)

  12. Hypertension and liver disease

    DEFF Research Database (Denmark)

    Henriksen, Jens H; Møller, Søren

    2004-01-01

    Arterial hypertension is a common disorder with a frequency of 10% to 15% in subjects in the 40- to 60-year age group. Yet most reports find the prevalence of arterial hypertension in patients with chronic liver disease (cirrhosis) much lower. In this review, we consider the alterations in systemic...

  13. Cirrhosis of the liver

    DEFF Research Database (Denmark)

    Bendtsen, Flemming; Larsen, Fin Stolze; Ott, Peter; Vilstrup, Hendrik

    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. 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.

  15. 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...

  16. 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....

  17. 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 ...

  18. 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 ...

  19. Nutritional Status and Liver Transplantation

    OpenAIRE

    Merli, Manuela; Giusto, Michela; Giannelli, Valerio; Lucidi, Cristina; Riggio, Oliviero

    2011-01-01

    Chronic liver disease has a profound effect on nutritional status and undernourishment is almost universally present in patients with end-stage liver disease undergoing liver transplantation. In the last decades, due to epidemiological changes, a trend showing an increase in patients with end-stage liver disease and associated obesity has also been reported in developed countries. Nutrition abnormalities may influence the outcome after transplantation therefore, the importance to carefully as...

  20. [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

  1. What Happens After Treatment for Liver Cancer?

    Science.gov (United States)

    ... Research Get Involved Find Local ACS Learn About Cancer » Liver Cancer » Detailed Guide » Living as a liver cancer ... Lifestyle changes after liver cancer Living as a liver cancer survivor Completing treatment can be both stressful and ...

  2. Liver regeneration and restoration of liver function after partial hepatectomy in patients with liver tumors

    International Nuclear Information System (INIS)

    Liver regeneration and restoration of liver function were studied in six patients who underwent partial hepatectomy with removal of 30-70% of the liver. Liver volume and liver regeneration were studied by single photon computed tomography (SPECT), using 99mTc-colloid as tracer. The method was assessed in 11 patients by comparing the pre- and post-operative volume measurement with the volume of the resected liver mass. Liver function was determined by measuring the galactose elimination capacity and the caffeine clearance. After a postoperative follow-up period of 50 days, the liver had regenerated maximally to a volume of 75 ± 2% of the preoperative liver mass. Maximal restoration of liver function was achieved 120 days after operation and amounted to 75 ± 10% for the caffeine clearance and to 100 ± 25% for the galactose elimination capacity. This study shows that SPECT is a useful method for assessing liver regeneration in patients after partial hepatectomy. The study furthermore shows that caffeine clearance correlates well with total liver volume, whereas the galactose elimination capacity overestimates total liver volume after partial hepatectomy. 22 refs

  3. 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.

  4. Research Progress of Liver Diseases

    Institute of Scientific and Technical Information of China (English)

    XU Lie-ming; JIA Ji-dong

    2005-01-01

    @@ Liver diseases are widespread in China.The disease mostly includes viral hepatitis,alcoholic or non alcoholic fatty degeneration or steatohepatitis, autoimmune liver disease,hepatic fibrosis/cirrhosis and hepatic cancer.The mechanism of most liver diseases was studied clearly in developed countries.

  5. Serum parameters of liver fibrosis

    NARCIS (Netherlands)

    R.A.A. van Zanten

    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 rec

  6. Stem cells in liver disease

    NARCIS (Netherlands)

    Poll, D. van

    2008-01-01

    Failure of the liver, the largest vital organ in the body, unequivocally results in death. Hepatic failure most commonly evolves over a period of several years as a result of chronic liver disease, most often viral hepatitis or alcoholic liver damage. In rarer cases, the organ shuts down within week

  7. Liver trauma: WSES position paper

    OpenAIRE

    Coccolini, Federico; Montori, Giulia; Catena, Fausto; Di Saverio, Salomone; Biffl, Walter; Moore, Ernest E; Peitzman, Andrew B; Rizoli, Sandro; Tugnoli, Gregorio; Sartelli, Massimo; Manfredi, Roberto; Ansaloni, Luca

    2015-01-01

    The liver is the most injured organ in abdominal trauma. Road traffic crashes and antisocial, violent behavior account for the majority of liver injuries. The present position paper represents the position of the World Society of Emergency Surgery (WSES) about the management of liver injuries.

  8. Improved transvenous liver biopsy needle

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Matzen, P; Christoffersen, P;

    1979-01-01

    A modified type of the standard transvenous cholangiography biopsy needle is described. The modified tranvenous liver biopsy needle caused only minimal artefactual changes of the liver biopsy specimens. The new type of biopsy needle is a modified Menghini needle. The conventional Menghini needle...... should be avoided for transvenous catheter biopsies because of risk of leaving catheter fragments in the liver....

  9. [Local treatment of liver tumors

    DEFF Research Database (Denmark)

    Pless, T.K.; Skjoldbye, Bjørn Ole

    2008-01-01

    Local treatment of non-resectable liver tumors is common. This brief review describes the local treatment techniques used in Denmark. The techniques are evaluated according to the evidence in literature. The primary local treatment is Radiofrequency Ablation of both primary liver tumors and liver...

  10. Systemic abnormalities in liver disease

    OpenAIRE

    Minemura, Masami; Tajiri, Kazuto; Shimizu, Yukihiro

    2009-01-01

    Systemic abnormalities often occur in patients with liver disease. In particular, cardiopulmonary or renal diseases accompanied by advanced liver disease can be serious and may determine the quality of life and prognosis of patients. Therefore, both hepatologists and non-hepatologists should pay attention to such abnormalities in the management of patients with liver diseases.

  11. Nonalcoholic fatty liver disease.

    Science.gov (United States)

    Brunt, Elizabeth M; Wong, Vincent W-S; Nobili, Valerio; Day, Christopher P; Sookoian, Silvia; Maher, Jacquelyn J; Bugianesi, Elisabetta; Sirlin, Claude B; Neuschwander-Tetri, Brent A; Rinella, Mary E

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a disorder characterized by excess accumulation of fat in hepatocytes (nonalcoholic fatty liver (NAFL)); in up to 40% of individuals, there are additional findings of portal and lobular inflammation and hepatocyte injury (which characterize nonalcoholic steatohepatitis (NASH)). A subset of patients will develop progressive fibrosis, which can progress to cirrhosis. Hepatocellular carcinoma and cardiovascular complications are life-threatening co-morbidities of both NAFL and NASH. NAFLD is closely associated with insulin resistance; obesity and metabolic syndrome are common underlying factors. As a consequence, the prevalence of NAFLD is estimated to be 10-40% in adults worldwide, and it is the most common liver disease in children and adolescents in developed countries. Mechanistic insights into fat accumulation, subsequent hepatocyte injury, the role of the immune system and fibrosis as well as the role of the gut microbiota are unfolding. Furthermore, genetic and epigenetic factors might explain the considerable interindividual variation in disease phenotype, severity and progression. To date, no effective medical interventions exist that completely reverse the disease other than lifestyle changes, dietary alterations and, possibly, bariatric surgery. However, several strategies that target pathophysiological processes such as an oversupply of fatty acids to the liver, cell injury and inflammation are currently under investigation. Diagnosis of NAFLD can be established by imaging, but detection of the lesions of NASH still depend on the gold-standard but invasive liver biopsy. Several non-invasive strategies are being evaluated to replace or complement biopsies, especially for follow-up monitoring. PMID:27188459

  12. Augmenter of liver regeneration

    Directory of Open Access Journals (Sweden)

    Gandhi Chandrashekhar R

    2012-07-01

    Full Text Available Abstract ‘Augmenter of liver regeneration’ (ALR (also known as hepatic stimulatory substance or hepatopoietin was originally found to promote growth of hepatocytes in the regenerating or injured liver. ALR is expressed ubiquitously in all organs, and exclusively in hepatocytes in the liver. ALR, a survival factor for hepatocytes, exhibits significant homology with ERV1 (essential for respiration and viability protein that is essential for the survival of the yeast, Saccharomyces cerevisiae. ALR comprises 198 to 205 amino acids (approximately 22 kDa, but is post-translationally modified to three high molecular weight species (approximately 38 to 42 kDa found in hepatocytes. ALR is present in mitochondria, cytosol, endoplasmic reticulum, and nucleus. Mitochondrial ALR may be involved in oxidative phosphorylation, but also functions as sulfhydryl oxidase and cytochrome c reductase, and causes Fe/S maturation of proteins. ALR, secreted by hepatocytes, stimulates synthesis of TNF-α, IL-6, and nitric oxide in Kupffer cells via a G-protein coupled receptor. While the 22 kDa rat recombinant ALR does not stimulate DNA synthesis in hepatocytes, the short form (15 kDa of human recombinant ALR was reported to be equipotent as or even stronger than TGF-α or HGF as a mitogen for hepatocytes. Altered serum ALR levels in certain pathological conditions suggest that it may be a diagnostic marker for liver injury/disease. Although ALR appears to have multiple functions, the knowledge of its role in various organs, including the liver, is extremely inadequate, and it is not known whether different ALR species have distinct functions. Future research should provide better understanding of the expression and functions of this enigmatic molecule.

  13. Liver transplantation in Spain.

    Science.gov (United States)

    de la Rosa, Gloria; Fondevila, Constantino; Navasa, Miquel

    2016-09-01

    Liver transplantation (LT) activity started in Spain in 1984 and has exceeded 23,700 interventions, with more than 1000 transplants performed yearly. Every hospital needs official authorization to perform a LT, which implies the obligation to register all patients on the national waiting list. The Spanish National Transplant Organization (ONT) provides essential support for organ procurement, allocation, and management of the waiting list at a national level. Liver allocation is center-oriented as all available organs are referred to the ONT for the whole country. The allocation rules for LT are made according to disease severity after consensus among professionals from every transplant center and ratified by representatives of the regional health authorities. Authorization and location/distribution of transplant centers are regulated by the country (Spain) and by the different regions according to the Real Decreto 1723/2012. For a total population of 47,850,795 inhabitants, there are 24 centers for LT for adults (1 team/2 million people) and 5 for LT for children (1 team/9.5 million people). Nonbiliary cirrhosis, particularly alcohol- and hepatitis C virus-related cirrhosis (60%), and tumors, mainly hepatocellular carcinoma (19%), are the most common indications for LT in Spain. Unusual causes of LT include metabolic diseases like Wilson's disease, familial amyloid polyneuropathy and hyperoxaluria type I, polycystic kidney and liver disease, and some tumors (epithelioid hemangioendothelioma and neuroendocrine tumors). Important efforts are now being undertaken to improve the quality and transplantability of extended criteria livers, in particular those arising from DCD, which represent the greatest opportunity to expand the donor pool. These efforts have to be addressed to adapt the organ preservation procedures, be it through the application of regional perfusion in situ or the use of machine perfusion preservation ex situ. Liver Transplantation 22 1259-1264 2016

  14. Neural net classification of liver ultrasonogram for quantitative evaluation of diffuse liver disease

    Science.gov (United States)

    Lee, Dong Hyuk; Kim, JongHyo; Kim, Hee C.; Lee, Yong W.; Min, Byong Goo

    1997-04-01

    There have been a number of studies on the quantitative evaluation of diffuse liver disease by using texture analysis technique. However, the previous studies have been focused on the classification between only normal and abnormal pattern based on textural properties, resulting in lack of clinically useful information about the progressive status of liver disease. Considering our collaborative research experience with clinical experts, we judged that not only texture information but also several shape properties are necessary in order to successfully classify between various states of disease with liver ultrasonogram. Nine image parameters were selected experimentally. One of these was texture parameter and others were shape parameters measured as length, area and curvature. We have developed a neural-net algorithm that classifies liver ultrasonogram into 9 categories of liver disease: 3 main category and 3 sub-steps for each. Nine parameters were collected semi- automatically from the user by using graphical user interface tool, and then processed to give a grade for each parameter. Classifying algorithm consists of two steps. At the first step, each parameter was graded into pre-defined levels using neural network. in the next step, neural network classifier determined disease status using graded nine parameters. We implemented a PC based computer-assist diagnosis workstation and installed it in radiology department of Seoul National University Hospital. Using this workstation we collected 662 cases during 6 months. Some of these were used for training and others were used for evaluating accuracy of the developed algorithm. As a conclusion, a liver ultrasonogram classifying algorithm was developed using both texture and shape parameters and neural network classifier. Preliminary results indicate that the proposed algorithm is useful for evaluation of diffuse liver disease.

  15. Hepatic clearance of 6 polyaromatic aromatic hydrocarbons by isolated trout livers: Prediction from in vitro clearance by liver S9 fractions

    Science.gov (United States)

    An isolated perfused trout liver preparation was used to evaluate in vitro-to-in vivo metabolism extrapolation procedures for fish. Hepatic clearance (CLH) studies were conducted with six polyaromatic hydrocarbons (PAH) using an experimental design wherein each liver acted as it...

  16. Induction of Th1Immune responses following laser ablation in a murine model of colorectal liver metastases

    OpenAIRE

    Muralidharan Vijayaragavan; Nikfarjam Mehrdad; Malcontenti-Wilson Caterina; Fifis Theodora; Lin Wen; Nguyen Linh; Christophi Christopher

    2011-01-01

    Abstract Background Preliminary experimental studies have suggested that the in situ destruction of tumor tissue by local laser ablation (LA) may also stimulate host immunity against cancer. We investigated local and systemic induction of immune responses after laser ablation in the setting of residual tumor. Methods A murine colorectal cancer (CRC) liver metastasis model was used. Selected tumors of liver CRC bearing mice and livers of mice without tumor induction were treated with LA. Liver...

  17. C8orf4 negatively regulates self-renewal of liver cancer stem cells via suppression of NOTCH2 signalling

    OpenAIRE

    Zhu, Pingping; Wang, Yanying; Du, Ying; He, Lei; Huang, Guanling; Zhang, Geng; Yan, Xinlong; Fan, Zusen

    2015-01-01

    Liver cancer stem cells (CSCs) harbour self-renewal and differentiation properties, accounting for chemotherapy resistance and recurrence. However, the molecular mechanisms to sustain liver CSCs remain largely unknown. In this study, based on analysis of several hepatocellular carcinoma (HCC) transcriptome datasets and our experimental data, we find that C8orf4 is weakly expressed in HCC tumours and liver CSCs. C8orf4 attenuates the self-renewal capacity of liver CSCs and tumour propagation. ...

  18. Observation of Liver Color Scan

    International Nuclear Information System (INIS)

    In the past few years, scintigraphy has become increasingly important in clinical practice, and the use of a color-printing technique has permitted a more accurate interpretation of the scan image. Our liver color scintigrams consist of 51 hepatomas, 35 liver cirrhosis, 22 liver abscesses, 10 hepatitis and other 13 cases of the liver diseases which were clinically and pathologically diagnosed at Severance Hospital, Yonsei Univ. since Feb. 1969 through Sept. 1969. These scintigrams have been analyzed in terms of various pathologic morphology, such as size, shape, margin of the liver, distribution of radioactivity, and shape of the space occupying lesions. The results are as follows: 1) Enlargement of the liver was the most common finding in the diseased livers. The Rt. lobe enlargement was particularly prominent in the liver abscess. 2) Irregular distribution of radioactivity in the liver (so called mottling) was present in 78% of hepatoma, while it was seen only in 31% of liver abscesses. 3) Liver cirrhosis tends to show perihilar accumulation of the isotope (57%). 4) The deformity of the lower most angle of the Rt. lobe, and the Lt. lateral margin of the Lt. lobe was also impressive throughout the cases (74-95% of all diseased livers). 5) The frequency of visualization of the spleen was influenced by the size of space occupying lesions and the amount of functioning liver. 6) Differentiation between the liver abscess and hepatoma seems to be possible on scintigram, when shape an margin of defect and patterns of distribution of radioactivity in the remaining liver are clearly demonstrated.

  19. Role of liver functions on liver cell mitosis

    Directory of Open Access Journals (Sweden)

    Takata,Tameyuki

    1974-06-01

    Full Text Available The control mechanism of mitosis in the regenerating rat liver was studied in relation to the cell functions. Partial hepatec· tomy induces a series of changes prior to the initiation of mitosis, i. e. decrease in serum glucose and albumin levels, loss of glycogen from liver cells, and increased lipid mobilization to liver cells. Massive supplies of glucose and fructose suppressed significantly hepatocellu. lar mitosis with suppression of lipid accumulation and preservation of glycogen in the liver cells and of blood sugar level. Homologous serum administration also suppressed the rate of liver cell mitosis after hepatectomy preventing the decrease in serum albumin level, but did not suppress the lipid accumulation in the liver. Starvation, which would relieve the liver cell from the work of detoxication of intesti. nal toxic products, did not show any suppressive effect on the mitotic rate of liver cells after partial hepatectomy in single animals. But starvation induced severe hypoglycemia, moderate hypoalbuminemia and loss of glycogen content in the liver. These changes in metabo. lism by starvation and partial hepatectomy were suppressed by con· jugating the animals with nonhepatectomized fed.partners by aortic anastomosis, and mitosis was suppressed in the residual liver of the fasting animals in this parabiosis. The results indicate that all the major functions of parenchymal live cells tested, sugar metabolism, serum albumin production, and detoxication, are closely related to the control of liver cell mitosis. Accumulation of lipids in the liver remnant after partial hepatectomy is thought to be for the compensa. tion of reduced glycogen storage and not concerned directly with the liver cell mitosis. Discussion was made briefly on the humoral factor and portal blood factor in relation to excess load of functions on resi. dual liver cells.

  20. A selective tropism of transfused oval cells for liver

    Institute of Scientific and Technical Information of China (English)

    Jian-Zhi Chen; Hai Hong; Jin Xiang; Ling Xue; Guo-Qiang Zhao

    2003-01-01

    AIM: To explore the biological behaviors of hepatic oval cells after transfused into the circulation of experimental animals.METHODS: Oval cells from male SD rat were transfused into the circulation of a female rat which were treated by a 2-AAF/CCl4 program, through caudal vein. Sex-determining gene sry which located on Y chromosome was examined by PCR and in situ hybridization technique in liver, kidney and spleen of the experimental animals, respectively.RESULTS: The results of the cell-transplant experiment showed that the srygene was detectable only in the liver but not in spleen and kidney of the experimental rats, and no signals could be detected in the control animals. It can be also morphologically proved that some exogenous cells had migrated into the parenchyma of the liver and settled there.CONCLUSION: The result means that there are exogenous cells located in the liver of the experimental animal and the localization is specific to the liver. This indicates that some "signal molecules" must exist in the circulation of the rats treated by 2-AAF/CCl4. These "signal molecules" might play an important role in specific localization and differentiation of transfused oval cells.

  1. Liver manifestations of cystic fibrosis

    International Nuclear Information System (INIS)

    Chronic liver disease is one of the major complications of cystic fibrosis (CF). Significant liver disease is seen in 13-25% of children with CF. Improved life expectancy and prolonged follow-up have favored better characterization of the hepatic manifestations of CF and allowed direct observation of an increasing number of liver-related events. Liver disease typically develops in the first decade of life, with the incidence dropping rapidly after the age of 10 years. The wide spectrum of liver disease ranging from asymptomatic gallbladder abnormalities to biliary cirrhosis will be reviewed in this article

  2. Autoimmune paediatric liver disease

    Directory of Open Access Journals (Sweden)

    Giorgina Mieli-Vergani, Diego Vergani

    2008-06-01

    Full Text Available Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH, autoimmune sclerosing cholangitis (ASC, and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1 or liver kidney microsomal antibody (LKM1, type 2. There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether

  3. Autoimmune paediatric liver disease

    Institute of Scientific and Technical Information of China (English)

    Giorgina Mieli-Vergani; Diego Vergani

    2008-01-01

    Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC),and de novo AIH after liver transplantation.AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA,type 1) or liver kidney microsomal antibody (LKM1,type 2).There is a female predominance in both.LKM1 positive patients tend to present more acutely,at a younger age,and commonly have partial IgA deficiency,while duration of symptoms before diagnosis,clinical signs,family history of autoimmunity, presence of associated autoimmune disorders,response to treatment,and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC.The clinical,biochemical, immunological,and histological presentation of ASC is often indistinguishable from that of AIH type 1.In both,there are high IgG,non-organ specific autoantibodies,and interface hepatitis.Diagnosis is made by cholangiography.Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates,times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However,the cholangiopathy can progress.There may be evolution from AIH to ASC over the years,despite treatment.De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH,including elevated titres of serum antibodies, hypergammaglobulinaemia,and histological findings of interface hepatitis,bridging fibrosis,and collapse.Like classical AIH,it responds to treatment with prednisolone and azathioprine.De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection.Whether this condition is a distinct entity or a form of

  4. Resveratrol Attenuates Both Small Bowel and Liver Changes in Obstructive Jaundice

    OpenAIRE

    Temi, Volkan; Okay, Erdem; Güneş, Abdullah; Şimşek, Turgay; Çekmen, Mustafa; Bilgili, Ümit

    2014-01-01

    Background: It is well known that mucosal changes and alterations in liver function occur in the experimental obstructive jaundice model. Aims: We aimed to evaluate the effect of resveratrol on obstructive jaundice-induced changes in the small bowel mucosa and liver using ischaemia-modified albumin as a marker of oxidative damage. Study Design: Animal experimentation. Methods: The study used a rodent experimental model of obstructive jaundice, including a sham gr...

  5. Endoderm specification and liver development.

    Science.gov (United States)

    Goessling, W; Stainier, D Y

    2016-01-01

    The endoderm is the innermost embryonic germ layer, and in zebrafish, it gives rise to the lining of the gut, the gills, liver, pancreas, gallbladder, and derivatives of the pharyngeal pouch. These organs form the gastrointestinal tract and are involved with the absorption, delivery, and metabolism of nutrients. The liver has a central role in regulating these processes because it controls carbohydrate and lipid metabolism, protein synthesis, and breakdown of endogenous and xenobiotic products. Liver dysfunction frequently leads to significant morbidity and mortality; however, in most settings of organ injury, the liver exhibits remarkable regenerative capacity. In this chapter, we review the principal mechanisms of endoderm and liver formation and provide protocols to assess liver formation and liver regeneration. PMID:27312502

  6. Probiotics in Pediatric Liver Disease.

    Science.gov (United States)

    Miloh, Tamir

    2015-01-01

    The gut-liver axis involves complex interaction between the intestinal microbiome and the liver parenchyma. Probiotics are live microorganisms that are used in a variety of diseases. With currently only 2 randomized-controlled studies (one with Lactobacillus GG and the other with VSL #3), data are scarce to support the clinical effect of probiotic use in children with nonalcoholic fatty liver disease. There is evidence that probiotics decrease the risk of necrotizing enterocolitis and thereby reduce the prevalence of total parenteral nutrition-induced chronic liver disease. Probiotics are used with a few reported positive outcomes in patients with cystic fibrosis and familial hypercholesterolemia and may be promising in other liver conditions. Probiotics are generally safe and well tolerated in children, premature infants, and in patients after liver transplantation. Large, prospective, randomized clinical trials are needed to evaluate the benefit of probiotics in children with liver diseases. PMID:26447962

  7. Lipids changes in liver cancer

    Institute of Scientific and Technical Information of China (English)

    JIANG Jing-ting; XU Ning; ZHANG Xiao-ying; WU Chang-ping

    2007-01-01

    Liver is one of the most important organs in energy metabolism.Most plasma apolipoproteins and endogenous lipids and lipoproteins are synthesized in the liver.It depends on the integrity of liver cellular function,which ensures homeostasis of lipid and lipoprotein metabolism.When liver cancer occurs,these processes are impaired and the plasma lipid and lipoprotein patterns may be changed.Liver cancer is the fifth common malignant tumor worldwide,and is closely related to the infections of hepatitis B virus (HBV) and hepatitis C virus (HCV).HBV and HCV infections are quite common in China and other Southeast Asian countries.In addition,liver cancer is often followed by a procession of chronic hepatitis or cirrhosis,so that hepatic function is damaged obviously on these bases,which may significantly influence lipid and lipoprotein metabolism in vivo.In this review we summarize the clinical significance of lipid and lipoprotein metabolism under liver cancer.

  8. Mitochondrial gene polymorphisms alter hepatic cellular energy metabolism and aggravate diet-induced non-alcoholic steatohepatitis

    Directory of Open Access Journals (Sweden)

    Torsten Schröder

    2016-04-01

    Conclusions: We observed distinct metabolic alterations in mice with a mitochondrial polymorphism associated hepatic mitochondrial dysfunction. However, a second hit, such as dietary stress, was required to cause hepatic steatosis and inflammation. This study suggests a causative role of hepatic mitochondrial dysfunction in the development of experimental NASH.

  9. Polycystic Liver Disease

    International Nuclear Information System (INIS)

    A 77-year-old African American male presented with intermittent abdominal pain for one week. He denied nausea, vomiting, diarrhea, constipation, fevers, anorexia, or weight loss. He denied a family history of liver disease, recent travel, or history of intravenous drug abuse. His vital signs were normal. Labs revealed total bilirubin of 1.5 mg/dl, hypoalbuminaemia 3.0 gm/dl and prolonged prothrombin time of 14.8 sec. Computed Tomography of the abdomen and pelvis with contrast showed multiple hepatic cysts with the largest cyst occupying the right abdomen, measuring 20.6 cm (Panel A and). This cyst had predominantly fluid attenuation, but also contained several septations. The patient underwent laparoscopic fenestration of the large hepatic cyst with hepatic cyst wall biopsy. Pathology revealed blood without malignant cells. The patient tolerated the procedure well with improvement of his abdominal pain and normalization of his liver function tests and coagulation profile

  10. Fatty liver in childhood

    Institute of Scientific and Technical Information of China (English)

    Yesim; Ozturk; Ozlem; Bekem; Soylu

    2014-01-01

    Fatty liver is a growing health problem worldwide. It might evolve to nonalcoholic steatohepatitis, cirrhosis and cause hepatocellular carcinoma. This disease, which has increased because of eating habits, changes in food content and lifestyle, affects people from childhood. The most important risk factors are obesity and insulin resistance. Besides these factors, gender, ethnicity, genetic predisposition and some medical problems are also important. Cirrhosis in children is rare but is reported. Nonalcoholic fatty liver disease(NAFLD) has no specific symptoms or signs but should be considered in obese children. NAFLD does not have a proven treatment. Weight loss with family based treatments is the most acceptable management. Exercise and an applicable diet with low glycemic index and appropriate calorie intake are preferred. Drugs are promising but not sufficient in children for today.

  11. Liver iron transport

    Institute of Scientific and Technical Information of China (English)

    Ross M Graham; Anita CG Chua; Carly E Herbison; John K Olynyk; Debbie Trinder

    2007-01-01

    The liver plays a central role in iron metabolism. It is the major storage site for iron and also expresses a complex range of molecules which are involved in iron transport and regulation of iron homeostasis. An increasing number of genes associated with hepatic iron transport or regulation have been identified. These include transferrin receptors (TFR1 and 2), a ferrireductase (STEAP3), the transporters divalent metal transporter-1 (DMT1) and ferroportin (FPN) as well as the haemochromatosis protein, HFE and haemojuvelin (HJV),which are signalling molecules. Many of these genes also participate in iron regulatory pathways which focus on the hepatic peptide hepcidin. However, we are still only beginning to understand the complex interactions between liver iron transport and iron homeostasis. This review outlines our current knowledge of molecules of iron metabolism and their roles in iron transport and regulation of iron homeostasis.

  12. Liver scintigraphy in ponies

    International Nuclear Information System (INIS)

    Six derivatives of ethylenediamine-N,N'-bis (alpha-2-hydroxy phenyl) acetic acid labeled with /sup 99m/Tc were prepared and their imaging qualities evaluated in ponies. The 6 agents produced good scintigraphic images of certain structures of the liver in the pony. For each agent, 13 different scans were taken. Dorsal views of the left lateral, right lateral, and quadrate lobe were obtained with dorsal scans. Left lateral and left lateral oblique (45 degrees) scans provided a left lateral view of the left lobe and a medial view of the right lateral lobe. Right lateral scans revealed the right lateral and quadrate lobes. Administration of /sup 99m/Tc-labeled colloids which are commonly used in other species for liver scintigraphy resulted in extensive lung uptake in the pony

  13. Liver Transplantation in Brazil.

    Science.gov (United States)

    Bittencourt, Paulo Lisboa; Farias, Alberto Queiroz; Couto, Claudia Alves

    2016-09-01

    Over 1700 liver transplantations (LTs) are performed annually in Brazil. In absolute terms, the country performs more LT surgeries than anywhere else in Latin America and is third worldwide. However, due to its increasing population and inadequate donor organ supply, the country averages 5-10 LTs per million population, far lower than required. There is a marked heterogeneity in organ donation and LT activity throughout the country. Access to LT in the underprivileged North, Midwest, and Northeast regions of Brazil is scarce. Major challenges for the future of LT in Brazil will be to increase organ donation and access to LT. The reduction of those geographical disparities in donation, organ procurement, and LT due to political and financial constraints is of utmost importance. Liver Transplantation 22 1254-1258 2016 AASLD. PMID:27228568

  14. Hypervascular liver lesions.

    Science.gov (United States)

    Kamaya, Aya; Maturen, Katherine E; Tye, Grace A; Liu, Yueyi I; Parti, Naveen N; Desser, Terry S

    2009-10-01

    Hypervascular hepatocellular lesions include both benign and malignant etiologies. In the benign category, focal nodular hyperplasia and adenoma are typically hypervascular. In addition, some regenerative nodules in cirrhosis may be hypervascular. Malignant hypervascular primary hepatocellular lesions include hepatocellular carcinoma, fibrolamellar carcinoma, and peripheral cholangiocarcinoma. Vascular liver lesions often appear hypervascular because they tend to follow the enhancement of the blood pool; these include hemangiomas, arteriovenous malformations, angiosarcomas, and peliosis. While most gastrointestinal malignancies that metastasize to the liver will appear hypovascular on arterial and portal-venous phase imaging, certain cancers such as metastatic neuroendocrine tumors (including pancreatic neuroendocrine tumors, carcinoid, and gastrointestinal stromal tumors) tend to produce hypervascular metastases due to the greater recruitment of arterial blood supply. Finally, rare hepatic lesions such as glomus tumor and inflammatory pseudotumor may have a hypervascular appearance. PMID:19842564

  15. Polycystic Liver Disease

    Energy Technology Data Exchange (ETDEWEB)

    Linda, Nguyen, E-mail: nguyenli@einstein.edu [5501 Old York Road, Philadelphia, PA 19141 (United States)

    2016-03-25

    A 77-year-old African American male presented with intermittent abdominal pain for one week. He denied nausea, vomiting, diarrhea, constipation, fevers, anorexia, or weight loss. He denied a family history of liver disease, recent travel, or history of intravenous drug abuse. His vital signs were normal. Labs revealed total bilirubin of 1.5 mg/dl, hypoalbuminaemia 3.0 gm/dl and prolonged prothrombin time of 14.8 sec. Computed Tomography of the abdomen and pelvis with contrast showed multiple hepatic cysts with the largest cyst occupying the right abdomen, measuring 20.6 cm (Panel A and). This cyst had predominantly fluid attenuation, but also contained several septations. The patient underwent laparoscopic fenestration of the large hepatic cyst with hepatic cyst wall biopsy. Pathology revealed blood without malignant cells. The patient tolerated the procedure well with improvement of his abdominal pain and normalization of his liver function tests and coagulation profile.

  16. Liver resection for cancer

    Institute of Scientific and Technical Information of China (English)

    RW Parks; OJ Garden

    2001-01-01

    STORY OF HEPATIC RESECTION The earliest hepatic surgery was almost exclusively performed for trauma with records from as for tumor were those of Langenbuch in 1888 [3] , Tiffany in 1890 [4],and Lucke in 1891[5].By1899,76 cases of liver resection had been reported with a mortality rate of 14.9% [6], a remarkably low figure for operations of this magnitude,all performed at the end of the 19th century.

  17. Osteodystrophy in liver cirrhosis

    International Nuclear Information System (INIS)

    In order to investigate the osteodystrophy in liver cirrhosis, 21 liver cirrhotic patients having no malignancy and normal renal function were examined by 99m Tc Methylene Diphosphonate (MDP) bone scintigraphy. The cirrhotic subjects consisted of 14 males and 7 females. Their age was 31 - 80, average 55.7 years. The causes of their cirrhotic damage were 1 primary biliary cirrhosis, 9 alcoholic, 2 HB viral and 9 cryptogenic. The contents of their illness showed 9 cases in A, 4 in B and 8 in C of Child's classification. Abnormal hot spot(s) on bone in the cirrhotics could be observed very frequently in 99m Tc MDP bone scintigraphy (47.6 %; 10/21 cases). Those spots were seen more frequently in female and advanced stage of cirrhosis. The number of spot(s) increased also in advanced liver cirrhosis. Serum Ca, P and PTH were in normal range. All of three vitamin D3 fractions decreased and especially 1,25 (OH)2D3 was depressed more in scinti-positive cases. Metacarpal bone X-p with an alumimum step wedge as a reference was analyzed by a microdensitometry (MD) method (Inoue T et al) and the pattern of osteopathy (i.e. porosis, malacia and poromalacia) was examined according to Sumi Y et al. MD method was not known yet if there was any definite correlation with bone scintigraphy and the osteopathic pattern belonged to border categories. In conclusion, more attension on hepatic osteodystrophy will be significantly necessary due to the fact that it has been found very frequently in liver cirrhosis. 99m Tc MDP bone scintigraphy is a good means for detection of the hepatic osteodystrophy. (author)

  18. 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......) database to extract demographics and outcomes of 58 PCLD patients. We used Kaplan-Meier survival analysis for survival rates. Severe abdominal pain (75%) was the most prominent symptom, while portal hypertension (35%) was the most common complication in PCLD. The explantation of the polycystic liver was...

  19. Effects of Kanlijian (坎离煎) on Exercise Tolerance, Quality of Life, and Frequency of Heart Failure Aggravation in Patients with Chronic Heart Failure

    Institute of Scientific and Technical Information of China (English)

    JIANG Mei-xian; RUAN Xiao-fen; XU Yan

    2006-01-01

    Objective: To observe the effects of conventional therapy combined with Kanlijian (坎离煎,KLJ) on exercise tolerance, quality of life and frequency of heart failure aggravation in patients with chronic heart failure(CHF). Methods: Sixty. CHF patients differentiated as sufferring from the syndrome of Xin-Shen Yang deficiency were included in the study and randomly assigned at the ratio of 2: 1 into the KLJ group (n=39) and the control group(n = 21). All the patients were treated with conventional therapy of Western medicine, but to those in the KLJ group, KLJ was medicated additionally one dose daily with 24 wks as one therapeutic course. The efficacy on TCM syndrome and changes of scores on TCM syndrome were observed after treatment. The indexes, including 6-minute walking distance (6MWD), quality of life (QOL, accessed by LHFQ scoring), NYHA grade, hemodynamic indexes and reducing/withdrawal rate of diuretic and digoxin before and after treatment were recorded and compared. Also the frequency of re-admission due to aggravation of heart failure in one year's time were observed. Results: ( 1 ) The efficacy on TCM syndrome, improvement on scores of TCM syndrome, therapeutic effects on 6MWD, QOL, and NYHA grade in the KLJ group were superior to those in the control group. (2) Hemodynamic indexes after treatment, left ventricular fractional shortening (LVFS) and E peak/A peak (E/A), between the two groups had no significant difference, while left ventricular ejection fraction (LVEF) was increased significantly in the KLJ group, but with no obvious change in the control group. (3) The reducing/withdrawal rate of diuretic and digoxin in the KLJ group was significantly higher than that in the control group. (4) The 1-year frequency of re-admission significantly decreased in the KLJ group. Conclusion: The adjuvant treatment of KLJ on the basis of Western conventional therapy can significantly improve CHF patients' exercise tolerance, quality of life and cardiac function

  20. The Involvement of Heat Shock Proteins in Murine Liver Regeneration

    Institute of Scientific and Technical Information of China (English)

    Qing Shi; Zhongjun Dong; Haiming Wei

    2007-01-01

    Partial hepatectomy (PHx) in mammals is a very common experimental model to investigate the process of liver regeneration. The surgery itself could give birth to a series of stresses, such as the temporary raise of body temperature and the ischaemia-reperfusion injury. Heat shock proteins (HSPs) were a family of stress-inducible proteins involved in maintaining cell homeostasis and regulating the immune system. In our study, we intended to investigate the expression and role of HSPs in liver regeneration. Using RT-PCR and Western blotting, we determined the expression in regenerating liver of HSP27, HSP60, HSP70 and HSP90 in mRNA level and protein level, respectively, with mice treated with sham operation as controls. We also used quercertin as an inhibitior of HSPs to explore their effects on liver regeneration. We found that hepatic expression of HSPs increased at the early phase of liver regeneration and declined to the constitutively low level later. Moreover, quercetin pretreatment delayed the progress of liver regeneration in mice via inhibition of HSPs. The results indicated that HSPs played an important role in liver regeneration.

  1. Management of liver trauma.

    LENUS (Irish Health Repository)

    Badger, S A

    2012-02-01

    BACKGROUND: Blunt and penetrating liver trauma is common and often presents major diagnostic and management problems. METHODS: A literature review was undertaken to determine the current consensus on investigation and management strategies. RESULTS: The liver is the most frequently injured organ following abdominal trauma. Immediate assessment with ultrasound has replaced diagnostic peritoneal lavage in the resuscitation room, but computerised tomography remains the gold standard investigation. Nonoperative management is preferred in stable patients but laparotomy is indicated in unstable patients. Damage control techniques such as perihepatic packing, hepatotomy plus direct suture, and resectional debridement are recommended. Major complex surgical procedures such as anatomical resection or atriocaval shunting are now thought to be redundant in the emergency setting. Packing is also recommended for the inexperienced surgeon to allow control and stabilisation prior to transfer to a tertiary centre. Interventional radiological techniques are becoming more widely used, particularly in patients who are being managed nonoperatively or have been stabilised by perihepatic packing. CONCLUSIONS: Management of liver injuries has evolved significantly throughout the last two decades. In the absence of other abdominal injuries, operative management can usually be avoided. Patients with more complex injuries or subsequent complications should be transferred to a specialist centre to optimise final outcome.

  2. Patogenesis of pipe-stem fibrosis of the liver (experimental observation on murine Schistosomiasis Patogenia da fibrose "pipe-stem" do fígado (observações experimentais na esquistossomose murina

    Directory of Open Access Journals (Sweden)

    Zilton A. Andrade

    1987-09-01

    Full Text Available Mice infected with 30 cercariae of Schistosoma mansoni developed portal and septal fibrosis due to the massive and concentrated deposition of eggs in the periportal areas which occurred following the 16th week after infection. The lesion resembled pipe-stem fibrosis seen in human hepatosplenic schistosomiasis in the following characters: portal fibrosis interconnecting portal spaces as well as portal spaces and central canals; portal inflammation; periovular granulomas; vascular obstruction and telangiectasia. The liver parenchyma maintained its normal architecture. Vascular injection techniques with Indian ink and vinylite revealed that the portal system developed numerous dilated collateral venules coming from the large and medium-sized portal branches, about 10 weeks after schistosome infection. The lodging of schistosome eggs into these collaterals resulted in granulomatous inflammation and fibrosis along all the portal tracts, thus forming the pipe-stem lesion. Although not readily demonstrable grossly, the pipe-stem fibrosis of murine schistosomiasis has many similarities with the human lesion and can be considered to have the same basic pathogenesis.Camundongos infectados com 30 cercárias do Schistosoma mansoni desenvolveram fibrose porta em virtude de um depósito progressivo e concentrado de ovos na região periportal, o que aconteceu a partir da 16ª semana da infecção. Esta fibrose certas características da chamada fibrose "pipe-stem" do homem vista na forma hepatoesplênica da esquistossomose, tais como obstrução das radiculas porta, telangiectasia, conexão fibrosa entre espaços porta e entre estes e veias centrais, além de certo grau de fibrose septal, presença dos granulomas em várias fases evolutivas e reação inflamatória crônica difusa, enquanto o parênquima hepático mantinha a sua estrutura lobular normal. As técnicas de injeção vascular com tinta da China e com vinilite feitas no sistema porta permitiram a

  3. Estudo comparativo do uso de cola de fibrina e cianoacrilato em ferimento de fígado de rato The repair of liver experimental wound with fibrin glue and cianoacrilate

    Directory of Open Access Journals (Sweden)

    Carlos Edmundo R. Fontes

    2004-01-01

    in 2 groups and submitted to the anesthesia with tiopental in the concentration of 40mg/kg EV. Laparotomy was made with exhibition of the liver. A punch of 3mm was made in the hepatic right lobe. The animals of group A were treated with the placement of fibrin glue in the wounds, the animals of group B had the wounds treated with cianoacrilate. In the 7th of post-operative period, under anesthesia, the animals suffered the resection of the right hepatic lobe and samples were collected for the histology study procedures (HE and Picro-Sirius. They were appraised for optical microscopy, the inflammatory response (qualitative criteria of the neutrofiles presence, giants cells, granuloma, neovascularization and for polarization microscopy, the quantification of collagen (I-young Type and III-matureType. RESULTS: The two adhesives had hemostatic effects in similar times.The wounds treated with fibrin glue showed larger amount of young and mature collagen and a larger amount of neovascularization, while the wounds treated with cianoacrilate showed larger reaction of granuloma. CONCLUSION: Fibrin glue and cianoacrilate have similar hemostatic effects.The wound treated with fibrin glue present larger neovascularization and larger percentage of collagen type I and type III showing tendency to a better tissue repair without formation of granuloma.

  4. Liver transplantation: fifty years of experience.

    Science.gov (United States)

    Song, Alice Tung Wan; Avelino-Silva, Vivian Iida; Pecora, Rafael Antonio Arruda; Pugliese, Vincenzo; D'Albuquerque, Luiz Augusto Carneiro; Abdala, Edson

    2014-05-14

    Since 1963, when the first human liver transplantation (LT) was performed by Thomas Starzl, the world has witnessed 50 years of development in surgical techniques, immunosuppression, organ allocation, donor selection, and the indications and contraindications for LT. This has led to the mainstream, well-established procedure that has saved innumerable lives worldwide. Today, there are hundreds of liver transplant centres in over 80 countries. This review aims to describe the main aspects of LT regarding the progressive changes that have occurred over the years. We herein review historical aspects since the first experimental studies and the first attempts at human transplantation. We also provide an overview of immunosuppressive agents and their potential side effects, the evolution of the indications and contraindications of LT, the evolution of survival according to different time periods, and the evolution of methods of organ allocation. PMID:24833866

  5. Bacterial translocation and changes in the intestinal microbiome associated with alcoholic liver disease

    OpenAIRE

    Yan, Arthur W.; Bernd Schnabl

    2012-01-01

    Alcoholic liver disease progresses through several stages of tissue damage, from simple steatosis to alcoholic hepatitis, fibrosis, or cirrhosis. Alcohol also affects the intestine, increases intestinal permeability and changes the bacterial microflora. Liver disease severity correlates with levels of systemic bacterial products in patients, and experimental alcoholic liver disease is dependent on gut derived bacterial products in mice. Supporting evidence for the importance of bacterial tran...

  6. Transcriptomic profiling of trichloroethylene exposure in male mouse liver

    Directory of Open Access Journals (Sweden)

    Yan Jiang

    2015-03-01

    Full Text Available Chronic Trichloroethylene (TCE exposure could induce hepatocellular carcinoma in mice, and occupational exposure in humans was suggested to be associated with liver cancer. To understand the role of non-genotoxic mechanism(s for TCE action, we examined the gene expression and DNA methylation changes in the liver of B6C3F1 mice orally administered with TCE for 5 days. As a beginning step, we profiled gene expression alterations induced by the TCE in mouse livers. Here we describe in detail the experimental methods, quality controls, and other information associated with our data deposited into Gene Expression Omnibus (GEO under GSE58819. Our data provide useful information for gene expression responses to TCE in mouse liver.

  7. Therapeutic Implications of Mesenchymal Stem Cells in Liver Injury

    Directory of Open Access Journals (Sweden)

    Maria Ausiliatrice Puglisi

    2011-01-01

    Full Text Available Mesenchymal stem cells (MSCs, represent an attractive tool for the establishment of a successful stem-cell-based therapy of liver diseases. A number of different mechanisms contribute to the therapeutic effects exerted by MSCs, since these cells can differentiate into functional hepatic cells and can also produce a series of growth factors and cytokines able to suppress inflammatory responses, reduce hepatocyte apoptosis, regress liver fibrosis, and enhance hepatocyte functionality. To date, the infusion of MSCs or MSC-conditioned medium has shown encouraging results in the treatment of fulminant hepatic failure and in end-stage liver disease in experimental settings. However, some issues under debate hamper the use of MSCs in clinical trials. This paper summarizes the biological relevance of MSCs and the potential benefits and risks that can result from translating the MSC research to the treatment of liver diseases.

  8. Mild hypothermia protects liver against ischemia and reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Cheng-You Wang; Yong Ni; Yan Liu; Zhi-Heng Huang; Min-Jie Zhang; Yong-Qiang Zhan; Hai-Bin Gao

    2005-01-01

    AIM: To determine whether mild hypothermia could protect liver against ischemia and reperfusion injury in pigs. METHODS: Twenty-four healthy pigs were randomly divided into normothermia, mild hypothermia and normal control groups. The experimental procedure consisted of temporary interruption of blood flow to total hepatic lobe for different lengths of time and subsequent reperfusion. Hepatic tissue oxygen pressure (PtiO2) and aspartate aminotransferase (AST) values were evaluated, and ultrastructural analysis was carried out for all samples.RESULTS: Serum AST was significantly lower, and hepatic P,O2 values were significantly higher in the mild hypothermia group than in the normothermia group during liver ischemiareperfusion periods (P = 0.032, P = 0.028). Meanwhile, the histopathologic injury of liver induced by ischemiareperfusion was significantly improved in the mild hypothermia group, compared with that in the normothermia group. CONCLUSION: Mild hypothermia can protect the liver from ischemia-reperfusion injury in pigs.

  9. Loss of p53 results in protracted electrographic seizures and development of an aggravated epileptic phenotype following status epilepticus

    OpenAIRE

    Engel, T.; K.Tanaka; Jimenez-Mateos, E M; Caballero-Caballero, A; Prehn, J. H. M.; HENSHALL, D. C.

    2010-01-01

    The p53 tumor suppressor is a multifunctional protein, which regulates cell cycle, differentiation, DNA repair and apoptosis. Experimental seizures up-regulate p53 in the brain, and acute seizure-induced neuronal death can be reduced by genetic deletion or pharmacologic inhibition of p53. However, few long-term functional consequences of p53 deficiency have been explored. Here, we investigated the development of epilepsy triggered by status epilepticus in wild-type and p53-deficient mice. Ana...

  10. Transplantable liver production plan: "Yamaton"--liver project, Japan.

    Science.gov (United States)

    Hata, Toshiyuki; Uemoto, Shinji; Kobayashi, Eiji

    2013-10-01

    Organ grafts developed in the xenogeneic pig scaffold are expected to resolve most issues of donor safety and ethical concerns about living-donor liver transplantation in Japan. We have been working on so-called "Yamaton" projects to develop transplantable organs using genetically engineered pigs. Our goal is to produce chimeric livers with human parenchyma in such pigs. The Yamaton-Liver project demonstrated the proof of concept by showing that rat-mouse chimeric livers could develop in mice and be successfully transplanted into syngeneic or allogeneic rats. Under conventional immunosuppression, the transplanted livers showed long-term function and protection against rejection. Because chimeric liver grafts have xenogeneic components, additional strategies, such as humanization of pig genes, induction of hematopoietic chimeras in donors, and replacement of pig endothelial cells with human ones, might be required in clinical use. Our projects still need to overcome various hurdles but can bring huge benefits to patients in the future. PMID:23896578

  11. Naproxen-induced liver injury

    Institute of Scientific and Technical Information of China (English)

    Sharif Ali; Jason D Pimentel; Chan Ma

    2011-01-01

    BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to induce liver injury. Patterns of the injury usually range from mild elevations of liver enzymes to sometimes severe fulminant hepatic failure. Likewise, naproxen is a propionic acid derivative NSAID that was introduced in 1980 and has been available as an over-the-counter medication since 1994, but has rarely been reported to cause liver injury. METHODS: We treated a 30-year-old woman with jaundice and intractablepruritusthatdevelopedshortlyaftertakingnaproxen. We reviewed the medical history and liver histopathology of the patient as well as all previously published case reports of naproxen-associated liver toxicity in the English language literature. RESULTS: The liver biochemical profile of the patient revealed a mixed cholestasis and hepatitis pattern. Consecutive liver biopsies demonstrated focal lobular inflammation, hepatocyte drop-out, and a progressive loss of the small interlobular bile ducts (ductopenia). The biopsy performed two years after onset of the disease showed partial recovery of a small number of bile ducts; however, 10 years passed before the biochemical profile returned to near normal. CONCLUSIONS:  Naproxen-associated liver toxicity remains a rare entity, but should be considered in any patient presenting with cholestasis shortly after its use. Liver injury is most commonly seen in a mixed pattern characterized by cholestasis and hepatitis. The resulting liver damage may take years to resolve.

  12. massive excision of liver

    Directory of Open Access Journals (Sweden)

    Dong-liang LI

    2014-10-01

    Full Text Available Objective To observe the promotion effect of bone mesenchymal stem cells (BMSCs transplantation and mobilized bone marrow stem cells on the recovery of liver function and liver tissue regeneration after massive partial hepatectomy in rats. Methods The rats were randomly divided into four groups after massive partial hepatectomy (about 85%, namely massive hepatectomy group (control group, n=15, received massive hepatectomy only, G-CSF group [n=15, received rhG-CSF 150μg/(kg•d by intraperitoneal injection after the operation for 5 days], MSCs group [n=15, received 5ml suspension of MSCs (about 1.5×106 by tail vein injection after the operation], and G-CSF+MSCs group [n=14, received 1.5ml suspension of MSCs (about 1.5×106 by tail vein injection and rhG-CSF 150μg/(kg•d by intraperitoneal injection for 5 days after the operation]. The CD34+ cells in the peripheral blood of the rats were assessed by flow cytometry after G-CSF mobilization. Liver function tests including ALT, AST and ALB were performed on the 3rd and 9th day after surgery. All the rats were sacrificed and liver tissue was harvested for histopathological study. The expression of Ki-67 and BrdU positive cells in the liver were determined by immunohistochemistry. Results Flow cytometric results identified the isolated cells were MSCs. BMSCs in peripheral blood significantly increased in number after rhG-CSF mobilization, and reaching the maximum number on the 5th day. After mobilization for 3, 5 and 9 days, the positive CD34 cells in G-CSF group were 0.009%, 0.016%, 0.019% respectively, which were higher than those in control group. The level of albumin was significantly elevated in three treatment groups compared with control group on the 9th day after the hepatectomy (P<0.05 or P<0.01. The expression of Ki-67 (110.16±27.64, 103.57±33.90, 98.52±21.87 vs 72.39±27.04 cells and BrdU positive cells (17.96±5.57, 16.45±5.75, 16.66±5.11 vs 11.72±3.83 cells in three

  13. Liver transplant in HCC

    Directory of Open Access Journals (Sweden)

    Sergio I. Duque Duque

    2007-02-01

    Full Text Available

     

    Hepatocellular carcinoma (HCC is the fifth most common cancer worldwide, and is the leading cause of death in cirrhotic individuals. 80% of HCC develops in cirrhotic patients. Unfortunately only 20 to 25% of patients can have a radical treatment, like resection, liver transplantation (LT, or percutaneous ablation. The other 75 to 80% of patients can only have supportive care.

    There is no evidence to establish the optimal first-line treatment for early HCC (one tumor of 5 cm or less, in patients with well preserved liver function, because of the lack of RCTs comparing these radical therapies. Resection and transplantation achieve a very good outcome (5-year survival of 60 to 70% but with very different recurrence rates (60-70% and 15-20% respectively. Due to the lack of liver donors, these two techniques compete as the first option for treatment in cirrhotic patients with well preserved liver function and only one tumor.

    There is no question in considering LT as the best option for patients with liver function impairment (Child-Pugh B-C patients and early tumors (less than three tumors of less than three centimeters. LT provides cure of both the neoplastic disease and the underlying liver disease. There are a few numbers of reports that shows a decrease in the overall survival, from an intention-to treat perspective as a result of the impact of dropouts from the waiting list because of death or progression. These numbers can be as high as 20%. Adjuvant therapies during the waiting period, although intuitively effective, have not had an impact on the outcome. Expansion of the accepted Milan criteria (single nodule <5 cm, two or three nodules <3 cm has been advocated by some groups

  14. Fentanyl-droperidol supplementation of rapid sequence induction in the presence of severe pregnancy-induced and pregnancy-aggravated hypertension.

    Science.gov (United States)

    Lawes, E G; Downing, J W; Duncan, P W; Bland, B; Lavies, N; Gane, G A

    1987-11-01

    Twenty-six patients manifesting severe pregnancy-induced (PIH) or pregnancy-aggravated (PAH) hypertension who presented for emergency Caesarean section under general anaesthesia were studied. All patients came from a previously identified high risk group--namely greater than 25 yr, multiparous and with diastolic arterial pressures sustained at greater than 120 mm Hg. Our standard accelerated induction technique for the management of severely hypertensive mothers was modified to include the use of fentanyl and droperidol before induction. This modification of the induction sequence produced a clinically significant amelioration of the reflex sympathetic hypertensive response to laryngoscopy and intubation in most mothers receiving antihypertensive therapy, without apparent deleterious effect in the immediate postoperative period to those neonates unaffected by intrauterine asphyxia. PMID:3689612

  15. Aggravation of atopic dermatitis in breast-fed infants by tree nut-related foods and fermented foods in breast milk.

    Science.gov (United States)

    Uenishi, Toshiaki; Sugiura, Hisashi; Tanaka, Toshihiro; Uehara, Masami

    2011-02-01

    Ninety-two exclusively breast-fed Japanese infants with atopic dermatitis were studied to see whether tree nut-related foods (chocolate and coffee) and fermented foods (cheese, yogurt, bread, soy sauce, miso soup and fermented soy beans) eaten by their mothers affected their skin condition. Of the 92 infants, 67 (73%) showed improvement of skin lesions when their mothers avoided these foods and showed aggravation of skin lesions when these foods were reintroduced. The predominant offending foods were chocolate, yogurt, soy sauce and miso soup. A long-term maternal exclusion of the trigger foods brought about progressive improvement of skin lesions in the majority of the infants. These findings suggest that tree nut-related foods and fermented foods are important offending foods of atopic dermatitis in breast-fed infants. PMID:21269309

  16. Human Cytomegalovirus-Encoded miR-US25-1 Aggravates the Oxidised Low Density Lipoprotein-Induced Apoptosis of Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Jianmin Fan

    2014-01-01

    Full Text Available Human cytomegalovirus (HCMV infection is linked to the development and severity of the cardiovascular disease atherosclerosis; however, there is little known about the promotion of atherosclerosis. miR-US25-1 is one of HCMV-encoded miRNAs and targets cellular genes that are essential for virus growth to control the life cycle of the virus and host cells. The prominent regulation on cell cycle genes of the miR-US25-1 attracts us to explore its role in the atherosclerosis promotion. It was indicated that miR-US25-1 level was upregulated in subjects or in endothelial cells with HCMV infection; and the miR-US25-1 downregulated the expression of BRCC 3 by targeting the 5′ UTR of BRCC 3. And a miR-US25-1 mimics transfection could reduce the EAhy926 cell viability but did not induce apoptosis in EAhy926 cells. And what is more, miR-US25-1 mimicis transfection deteriorated the ox-LDL-induced apoptosis and aggravated the upregulation of apoptosis-associated molecules by oxidised low density lipoprotein (ox-LDL in EAhy926 cells. And we have also confirmed the deregulation of BRCC 3 expression by miR-US25-1 by targeting the 5′ UTR of it. Given the vital role of BRCC 3 in DNA damage repairing, we speculated that the targeting inhibition of BRCC 3 by miR-US25-1 may contribute to the aggravation of ox-LDL-promoted apoptosis of endothelial EAhy926 cells.

  17. Alcoholic liver disease and the gut-liver axis

    Institute of Scientific and Technical Information of China (English)

    Gyongyi; Szabo; Shashi; Bala

    2010-01-01

    Alcoholic liver disease (ALD) is one of the leading causes of liver diseases and liver-related death worldwide. Of the many factors that contribute to the pathogenesis of ALD, gut-derived lipopolysaccharide (LPS) plays a central role in induction of steatosis, inflammation, and fi brosis in the liver. In this review, we discuss the mechanisms by which alcohol contributes to increased gut permeability, the activation of Kupffer cells, and the infl ammatory cascade by LPS. The role of the Toll-like receptor 4...

  18. Celecoxib-induced cholestatic liver failure requiring orthotopic liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Ihab I El Hajj; Shahid M Malik; Hany R Alwakeel; Obaid S Shaikh; Eizaburo Sasatomi; Hossam M Kandil

    2009-01-01

    Selective cyclooxygenase-2 (COX-2) inhibitors are widely used due to their efficacy and good safety profile.However, recent case reports have described varying degrees of liver injuries associated with the use of COX-2 inhibitors. We report the case of a patient who developed acute cholestatic hepatitis progressing to hepatic failure requiring liver transplantation, following a 3-d course of celecoxib for treatment of generalized muscle aches and pains. The clinical presentation, the laboratory data, as well as the liver histopathology were supportive of the putative diagnosis of drug induced liver injury.

  19. The types of hepatic myofibroblasts contributing to liver fibrosis of different etiologies.

    Directory of Open Access Journals (Sweden)

    JunXu

    2014-07-01

    Full Text Available Liver fibrosis results from dysregulation of normal wound healing, inflammation, activation of myofibroblasts and deposition of extracellular matrix (ECM. Chronic liver injury causes death of hepatocytes and formation of apoptotic bodies, which in turn, release factors that recruit inflammatory cells (neutrophils, monocytes, macrophages, and lymphocytes to the injured liver. Hepatic macrophages (Kupffer cells produce TGF1 and other inflammatory cytokines that activate Collagen Type I producing myofibroblasts, which are not present in the normal liver. Secretion of TGF1 and activation of myofibroblasts play a critical role in the pathogenesis of liver fibrosis of different etiologies. Although the composition of fibrogenic myofibroblasts varies dependent on etiology of liver injury, liver resident Hepatic Stellate Cells (HSCs and Portal Fibroblasts (PFs are the major source of myofibroblasts in fibrotic liver in both experimental models of liver fibrosis and in patients with liver disease. Several studies have demonstrated that hepatic fibrosis can reverse upon cessation of liver injury. Regression of liver fibrosis is accompanied by the disappearance of fibrogenic myofibroblasts followed by resorption of the fibrous scar. Myofibroblasts either apoptose or inactivate into a quiescent-like state (e.g. stop collagen production and partially restore expression of lypogenic genes. Resolution of liver fibrosis is associated with recruitment of macrophages that secrete matrix-degrading enzymes (matrix metalloproteinase, collagenases and are responsible for fibrosis resolution. However, prolonged/repeated liver injury may cause irreversible crosslinking of ECM and formation of uncleavable collagen fibers. Advanced fibrosis progresses to cirrhosis and hepatocellular carcinoma (HCC. The current review will summarize the role and contribution of different cell types to populations of fibrogenic myofibroblasts in fibrotic liver.

  20. An acqueous extract of Bidens pilosa L. protects liver from cholestatic disease: experimental study in young rats Um extrato aquoso de Bidens pilosa L. protege o fígado da doença colestática: estudo experimental em ratos jovens

    Directory of Open Access Journals (Sweden)

    Marta Izabel Suzigan

    2009-10-01

    Full Text Available PURPOSE: To test the hepatoprotective effect of water extract from Bidens Pilosa L. (BPE in cholestatic liver disease induced by ligature and resection of the common bile ducts (LRBD in young rats. METHODS: We studied four groups of ten 21 days old (P21 Wistar rats, Group SW: sham operation and water; Group SD: sham operation and BPE (160 mg of fresh leaves/100 g of body weight/day; Group LW: LRBD and water and Group LD: LRBD and BPE daily. Pentobarbital sleeping time (PST and serum activities of aspartate aminotransferase (AST and of alanine aminotransferase (ALT were determined after the sacrifice (P70. A Ruwart's score for hepatic fibrosis (RS was given to each animal. Were employed two way ANOVA and the test of Tukey or a non-parametric test for multiple comparisons. RESULTS: There were statistically significant differences between LW and LD in the measurements of the PST ((means LW=390; LD=173, AST (means LW=8, LD=5, ALT (medians LW=2; LD=1 e RS (medians LW=2; LD=1. CONCLUSION: BPE could be used in the phytotherapy of the hepatic damage induced by chronic obstructive cholestasis, because protects liver function, decreases the rate of necrosis and liver fibrosis in cholestatic liver disease.OBJETIVO: Testar o efeito hepatoprotetor do extrato aquoso de Bidens pilosa L. (EBP na doença hepática induzida pela ligadura e ressecção do ducto biliar comum (LRDBC em ratos jovens. MÉTODOS: Estudamos ratos Wistar com 21º. dia de vida (P21 divididos em quatro grupos de 10 animais, Grupo SA: operação simulada e água; Grupo SD: operação simulada e EBP (160mg de folhas frescas/100g de peso corporal/dia; Grupo LA: LRDBC e água e Grupo LD: LRDBC e EBP diariamente. O tempo de sono por pentobarbital (TSP, aspartato (AST e alanina (ALT aminotransferase foram determinadas após o sacrifício (P70. O Score de Ruwart (SR para fibrose hepática foi atribuído para cada animal. Foi realizada análise de variância com dois fatores e pelo teste de Tukey