Sample records for ethanol-induced hepatic damage

  1. Effect of exercise training on ethanol-induced oxidative damage in aged rats.

    PubMed

    Mallikarjuna, K; Nishanth, K; Hou, Chien-Wen; Kuo, Chia-Hua; Sathyavelu Reddy, K

    2009-02-01

    It is well known that lipid peroxidation increases with age, and alcohol drinking further exacerbates this damage. The present study determined the effect of regular exercise training on alcohol-induced oxidative damage and antioxidant status in the liver of aged animals. The age-matched Wistar albino rats (3 months young, n=24; 18 months old, n=24) were evenly divided into four groups: control (C), exercise trained (Ex), ethanol drinking (Et), and exercise plus ethanol drinking (Ex+Et). With ethanol drinking, hepatic malondialdehyde (MDA) level was significantly elevated above control (P<.001), whereas glutathione (GSH) and ascorbic acid (vitamin C) contents were significantly decreased below control. These changes were found to be greater in the aged rats than those of the young rats. For both age groups, exercise training significantly reversed the increase in MDA and decreases in GSH and ascorbic acid induced by ethanol drinking. The present study showed that ethanol-induced deterioration in lipid peroxidation and reduction in antioxidant status in the liver were exacerbated with age. Here, we found that exercise training significantly reversed the adverse conditions that were caused by ethanol in aged rats. PMID:19185211

  2. Preventive Effect of the Flavonoid, Wogonin, Against Ethanol-Induced Gastric Mucosal Damage in Rats

    Microsoft Academic Search

    Soojin Park; Ki-Baik Hahm; Tae-Young Oh; Joo-Hyun Jin; Ryowon Choue

    2004-01-01

    Whether wogonin (5,7-dihydroxy-8-methoxyflavone), a flavonoid originated from the root of Scutellaria baicalensis Georgi, which has been shown to have antiinflammatory and antitumor activities in various cell types, possesses a gastric cytoprotective effect was investigated in an ethanol-induced gastric damage model in rats. Ethanol administration alone induced evident gastric damage including gastric hemorrhages and edema, while this gastric damage was significantly

  3. A novel role for GAPDH-MAO B cascade in ethanol-induced cellular damage

    PubMed Central

    Ou, Xiao-Ming; Stockmeier, Craig A.; Meltzer, Herbert Y.; Overholser, James C.; Jurjus, George J.; Dieter, Lesa; Chen, Kevin; Lu, Deyin; Johnson, Chandra; Youdim, Moussa B.H.; Austin, Mark C.; Luo, Jia; Sawa, Akira; May, Warren; Shih, Jean C.

    2009-01-01

    Background Alcoholism is a major psychiatric condition at least partly associated with ethanol-induced cell damage. Although brain cell loss has been reported in subjects with alcoholism, the molecular mechanism is unclear. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and monoamine oxidase B (MAO B) reportedly play a role in cellular dysfunction under stressful conditions and may contribute to ethanol-induced cell damage. Methods Expression of GAPDH and MAO B protein was studied in human glioblastoma and neuroblastoma cell lines exposed to physiological concentrations of ethanol. Expression of these proteins was also examined in the prefrontal cortex from human subjects with alcohol dependence and in rats fed with an ethanol diet. Co-immunoprecipitation, subcellular fractionation, and luciferase assay were used to address nuclear GAPDH-mediated MAO B activation. To test the effects of inactivation, RNAi and pharmacological intervention were used, and cell damage was assessed by TUNEL and H2O2 measurements. Results Ethanol significantly increases levels of GAPDH, especially nuclear GAPDH, and MAO B in neuronal cells as well as in human and rat brains. Nuclear GAPDH interacts with the transcriptional activator, transforming growth factor-beta-inducible early gene 2 (TIEG2), and augments TIEG2-mediated MAO B transactivation, which results in cell damage in neuronal cells exposed to ethanol. Knockdown expression of GAPDH or treatment with MAO B inhibitors selegiline (Deprenyl) and rasagiline (Azilect) can block this cascade. Conclusions Ethanol-elicited nuclear GAPDH augments TIEG2-mediated MAO B, which may play a role in brain damage in subjects with alcoholism. Compounds that block this cascade are potential candidates for therapeutic strategies. PMID:20022592

  4. PPAR?/? modulates ethanol-induced hepatic effects by decreasing pyridoxal kinase activity

    PubMed Central

    Goudarzi, Maryam; Koga, Takayuki; Khozoie, Combiz; Mak, Tytus D.; Kang, Boo-Hyon; Fornace, Albert J.; Peters, Jeffrey M.

    2013-01-01

    Because of the significant morbidity and lethality caused by alcoholic liver disease (ALD), there remains a need to elucidate the regulatory mechanisms that can be targeted to prevent and treat ALD. Towards this goal, minimally invasive biomarker discovery represents an outstanding approach for these purposes. The mechanisms underlying ALD include hepatic lipid accumulation. As the peroxisome proliferator-activated receptor-?/? (PPAR?/?) has been shown to inhibit steatosis, the present study examined the role of PPAR?/? in ALD coupling metabolomic, biochemical and molecular biological analyses. Wild-type and Ppar?/?-null mice were fed either a control or 4% ethanol diet and examined after 4–7 months of treatment. Ethanol fed Ppar?/?-null mice exhibited steatosis after short-term treatment compared to controls, the latter effect appeared to be due to increased activity of sterol regulatory element binding protein 1c (SREBP1c). The wild-type and Ppar?/?-null mice fed the control diet showed clear differences in their urinary metabolomic profiles. In particular, metabolites associated with arginine and proline metabolism, and glycerolipid metabolism, were markedly different between genotypes suggesting a constitutive role for PPAR?/? in the metabolism of these amino acids. Interestingly, urinary excretion of taurine was present in ethanol-fed wild-type mice but markedly lower in similarly treated Ppar?/?-null mice. Evidence suggests that PPAR?/? modulates pyridoxal kinase activity by altering Km, consistent with the observed decreased in urinary taurine excretion. These data collectively suggest that PPAR?/? prevents ethanol-induced hepatic effects by inhibiting hepatic lipogenesis, modulation of amino acid metabolism, and altering pyridoxal kinase activity. PMID:23851158

  5. The effect of thalidomide on ethanol-induced gastric mucosal damage in mice: involvement of inflammatory cytokines and nitric oxide.

    PubMed

    Amirshahrokhi, Keyvan; Khalili, Ali-Reza

    2015-01-01

    Excessive ethanol ingestion causes gastric mucosal damage through the inflammatory and oxidative processes. The present study was aimed to evaluate the protective effect of thalidomide on ethanol-induced gastric mucosal damage in mice. The animals were pretreated with vehicle or thalidomide (30 or 60 mg/kg, orally), and one hour later, the gastric mucosal injury was induced by oral administration of acidified ethanol. The animals were euthanized one hour after ethanol ingestion, and gastric tissues were collected to biochemical analyzes. The gastric mucosal lesions were assessed by macroscopic and histopathological examinations. The results showed that treatment of mice with thalidomide prior to the administration of ethanol dose-dependently reduced the gastric ulcer index. Thalidomide pretreatment significantly reduced the levels of pro-inflammatory cytokines [tumor necrosis factor (TNF)-?, interleukin (IL)-1?, IL-6], malondialdehyde (MDA) and myeloperoxidase (MPO) activity. In addition, thalidomide significantly inhibited ethanol-induced nitric oxide (NO) overproduction in gastric tissue. Histological observations showed that ethanol-induced gastric mucosal damage was attenuated by thalidomide pretreatment. It seems that thalidomide as an anti-inflammatory agent may have a protective effect against alcohol-induced mucosal damage by inhibition of neutrophil infiltration and reducing the production of nitric oxide and inflammatory cytokines in gastric tissue. PMID:25478868

  6. Effects of Rumex patientia root extract on indomethacine and ethanol induced gastric damage in rats.

    PubMed

    Süleyman, H; Demirezer, L O; Kuruüzüm-Uz, A

    2004-02-01

    The effects of an aqueous root extract from Rumex patientia (D-1) compared to COX-2 selective inhibitors on indomethacine and ethanol induced stomach ulcers were investigated. Adult male Wistar albino rats, weighing between 185-200 g were used. It was determined that D-1 does not show its gastroprotective activity via a COX enzyme in indomethacine induced ulcers. Antioxidant effects protect the gastrointestinal system. The effect of D-1 in ethanol induced ulcers may also be due to its antioxidant effect. PMID:15025185

  7. Solanesol protects human hepatic L02 cells from ethanol-induced oxidative injury via upregulation of HO-1 and Hsp70.

    PubMed

    Yao, Xiangyang; Bai, Qin; Yan, Dazhong; Li, Guilan; Lü, Chaotian; Xu, Hui

    2015-04-01

    In present study, we showed that the mRNA and protein levels of HO-1 and Hsp70 in solanesol-treated L02 cells were significantly increased. The induction of the HO-1 by solanesol is majorly achieved via enhancing the nuclear translocation and transactivity of Nrf2 through enhancement of Hsp90-Keap1 interaction, while solanesol-elevated Hsp70 is related with promoting the nuclear translocation of HSF1 through the involvement of chaperones interaction. Furthermore, the induction of HO-1 and Hsp70 by solanesol could protect against ethanol-induced liver injury, including significantly suppressing the elevation of the activities of LDH and AST, attenuating ethanol-induced increase of the MDA, ROS level and decrease of the GSH level. Moreover, solanesol also suppressed ethanol-induced apoptosis of L02 cells by inhibition of nuclear morphological damage, procaspase 3 and cleavage of caspase 3 and PARP, suggesting solanesol may be beneficial against ALD. Solanesol also promoted tBHQ-mediated protective effects. However, treatment cells with SnPP or PES markedly abrogated the protective effects of solanesol on ethanol-induced cell injury. These results strongly suggested that solanesol could protect ethanol-induced L02 cell damage, which might be attributed to the activation of HO-1 and Hsp70. PMID:25645596

  8. Sulfated-Polysaccharide Fraction from Red Algae Gracilaria caudata Protects Mice Gut Against Ethanol-Induced Damage

    PubMed Central

    Silva, Renan Oliveira; dos Santos, Geice Maria Pereira; Nicolau, Lucas Antonio Duarte; Lucetti, Larisse Tavares; Santana, Ana Paula Macedo; de Souza Chaves, Luciano; Barros, Francisco Clark Nogueira; Freitas, Ana Lúcia Ponte; Souza, Marcellus Henrique Loiola Ponte; Medeiros, Jand-Venes Rolim

    2011-01-01

    The aim of the present study was to investigate the gastroprotective activity of a sulfated-polysaccharide (PLS) fraction extracted from the marine red algae Gracilaria caudata and the mechanism underlying the gastroprotective activity. Male Swiss mice were treated with PLS (3, 10, 30 and 90 mg·kg?1, p.o.), and after 30 min, they were administered 50% ethanol (0.5 mL/25 g?1, p.o.). One hour later, gastric damage was measured using a planimeter. Samples of the stomach tissue were also obtained for histopathological assessment and for assays of glutathione (GSH) and malondialdehyde (MDA). Other groups were pretreated with l-NAME (10 mg·kg?1, i.p.), dl-propargylglycine (PAG, 50 mg·kg?1, p.o.) or glibenclamide (5 mg·kg?1, i.p.). After 1 h, PLS (30 mg·kg?1, p.o.) was administered. After 30 min, ethanol 50% was administered (0.5 mL/25g?1, p.o.), followed by sacrifice after 60 min. PLS prevented-ethanol-induced macroscopic and microscopic gastric injury in a dose-dependent manner. However, treatment with l-NAME or glibenclamide reversed this gastroprotective effect. Administration of propargylglycine did not influence the effect of PLS. Our results suggest that PLS has a protective effect against ethanol-induced gastric damage in mice via activation of the NO/KATP pathway. PMID:22163181

  9. Betaine treatment attenuates chronic ethanol-induced hepatic steatosis and alterations to the mitochondrial respiratory chain proteome.

    PubMed

    Kharbanda, Kusum K; Todero, Sandra L; King, Adrienne L; Osna, Natalia A; McVicker, Benita L; Tuma, Dean J; Wisecarver, James L; Bailey, Shannon M

    2012-01-01

    Introduction. Mitochondrial damage and disruption in oxidative phosphorylation contributes to the pathogenesis of alcoholic liver injury. Herein, we tested the hypothesis that the hepatoprotective actions of betaine against alcoholic liver injury occur at the level of the mitochondrial proteome. Methods. Male Wister rats were pair-fed control or ethanol-containing liquid diets supplemented with or without betaine (10?mg/mL) for 4-5 wks. Liver was examined for triglyceride accumulation, levels of methionine cycle metabolites, and alterations in mitochondrial proteins. Results. Chronic ethanol ingestion resulted in triglyceride accumulation which was attenuated in the ethanol plus betaine group. Blue native gel electrophoresis (BN-PAGE) revealed significant decreases in the content of the intact oxidative phosphorylation complexes in mitochondria from ethanol-fed animals. The alcohol-dependent loss in many of the low molecular weight oxidative phosphorylation proteins was prevented by betaine supplementation. This protection by betaine was associated with normalization of SAM?:?S-adenosylhomocysteine (SAH) ratios and the attenuation of the ethanol-induced increase in inducible nitric oxide synthase and nitric oxide generation in the liver. Discussion/Conclusion. In summary, betaine attenuates alcoholic steatosis and alterations to the oxidative phosphorylation system. Therefore, preservation of mitochondrial function may be another key molecular mechanism responsible for betaine hepatoprotection. PMID:22187660

  10. Ethanol-induced changes in hepatic free radical defense mechanisms and fatty-acid composition in the miniature pig.

    PubMed

    Zidenberg-Cherr, S; Olin, K L; Villanueva, J; Tang, A; Phinney, S D; Halsted, C H; Keen, C L

    1991-06-01

    In the miniature pig, ethanol consumption has been reported to induce alterations in hepatic antioxidant defense capacity, which could result in increased risk of peroxidative damage. However, ethanol may also induce changes in membrane fatty acid composition, which could reduce the risk of peroxidative damage. This study examined lipid peroxidation, antioxidant defense and fatty acid composition in livers from miniature pigs fed ethanol in diets containing 12% of their calories as fat for 20 mo. After 12 and 20 mo of feeding, ethanol-fed pigs had higher hepatic manganese-superoxide dismutase activity, lower hepatic copper concentrations and low hepatic copper-zinc-superoxide dismutase and glutathione peroxidase activities compared with controls. Lipid peroxidation as assessed by thiobarbituric acid reacting substance assay was lower in liver homogenate and mitochondrial and microsomal fractions from ethanol-fed pigs than in controls. The percentage contribution of highly unsaturated fatty acids to total fatty acids in liver homogenates (after 12 mo of feeding) and microsome fractions (after 20 mo of feeding) was lower in the ethanol-fed pigs than in the controls, resulting in a lower peroxidizability index. Ethanol-fed pigs had minimal or no hepatic damage as assessed by histological methods. We suggest that the relative resistance of microsomes to lipid peroxidation is due to the lower peroxidizability index in the ethanol-fed pigs and may account in part for the absence of significant histopathological findings after 20 mo of ethanol feeding. PMID:2050333

  11. Protective effect of anacardic acids from cashew (Anacardium occidentale) on ethanol-induced gastric damage in mice.

    PubMed

    Morais, Talita C; Pinto, Natália B; Carvalho, Karine Maria M B; Rios, Jeison B; Ricardo, Nagila Maria P S; Trevisan, Maria Teresa S; Rao, Vietla S; Santos, Flávia A

    2010-01-01

    Cashew nut-shell liquid and the contained anacardic acids (AAs) have been shown to possess antioxidant, lipoxygenase inhibitory, anti-Helicobacter pylori and antitumor properties. Despite these known effects, hitherto there were no published reports on their likely gastroprotective effects. The present study was designed to verify whether AAs afford gastroprotection against the ethanol-induced gastric damage and to examine the underlying mechanism(s). Gastric damage was induced by intragastric administration of 0.2mL of ethanol (96%). Mice in groups were pretreated orally with AAs (10, 30 and 100mg/kg), misoprostol (50 microg/kg), or vehicle (2% Tween 80 in saline, 10mL/kg), 45min before ethanol administration. They were sacrificed 30min later, the stomachs excised, and the mucosal lesion area (mm(2)) measured by planimetry. Gastroprotection was assessed in relation to inhibition of gastric lesion area. To study the gastroprotective mechanism(s), its relations to capsaicin-sensitive fibers, endogenous prostaglandins, nitric oxide and ATP-sensitive potassium channels were analysed. Treatments effects on ethanol-associated oxidative stress markers GSH, MDA, catalase, SOD, and total nitrate/nitrite levels as an index of NO were measured in gastric tissue. Besides, the effects of AAs on gastric secretory volume and total acidity were analysed in 4-h pylorus-ligated rat. AAs afforded a dose-related gastroprotection against the ethanol damage and further prevented the ethanol-induced changes in the levels of GSH, MDA, catalase, SOD and nitrate/nitrite. However, they failed to modify the gastric secretion or the total acidity. It was observed that the gastroprotection by AAs was greatly reduced in animals pretreated with capsazepine, indomethacin, l-NAME or glibenclamide. These results suggest that AAs afford gastroprotection principally through an antioxidant mechanism. Other complementary mechanisms include the activation of capsaicin-sensitive gastric afferents, stimulation of endogenous prostaglandins and nitric oxide, and opening of K(+)(ATP) channels. These combined effects are likely to be accompanied by an increase in gastric microcirculation. PMID:19853593

  12. Ethanol-induced hepatic steatosis is modulated by glycogen level in the liver.

    PubMed

    Gu, Jin; Zhang, Yongxian; Xu, Daqian; Zhao, Zilong; Zhang, Yuxue; Pan, Yi; Cao, Peijuan; Wang, Zhenzhen; Chen, Yan

    2015-07-01

    Alcoholic liver disease (ALD) is a major health problem worldwide and hepatic steatosis is an early response to alcohol consumption. Fat and glycogen are two major forms of energy storage in the liver; however, whether glycogen metabolism in the liver impacts alcohol-induced steatosis has been elusive. In this study, we used a mouse model with overexpression of PPP1R3G in the liver to dissect the potential role of glycogen on alcohol-induced fatty liver formation. PPP1R3G is a regulatory subunit of protein phosphatase 1 and stimulates glycogenesis in the liver. Chronic and binge ethanol (EtOH) feeding reduced glycogen level in the mouse liver and such inhibitory effect of EtOH was reversed by PPP1R3G overexpression. In addition, PPP1R3G overexpression abrogated EtOH-induced elevation of serum levels of alanine aminotransferase and aspartate aminotransferase, increase in liver triglyceride concentration, and lipid deposition in the liver. EtOH-stimulated sterol regulatory element-binding protein (SREBP)-1c, a master regulator of lipogenesis, was also reduced by PPP1R3G overexpression in vivo. In AML-12 mouse hepatocytes, PPP1R3G overexpression could relieve EtOH-induced lipid accumulation and SREBP-1c stimulation. In conclusion, our data indicate that glycogen metabolism is closely linked to EtOH-induced liver injury and fatty liver formation. PMID:26022806

  13. Hepatoprotective activity of Peganum harmala against ethanol-induced liver damages in rats.

    PubMed

    Bourogaa, Ezzeddine; Jarraya, Raoudha Mezghani; Damak, Mohamed; Elfeki, Abdelfattah

    2015-05-01

    In this study, we investigated the protective effects of Peganum harmala seeds extract (CPH) against chronic ethanol treatment. Hepatotoxicity was induced in male Wistar rats by administrating ethanol 35% (4?g/kg/day) for 6 weeks. CPH was co-administered with ethanol, by intraperitonial (IP) injection, at a dose of 10?mg/kg bw/day. Control rats were injected by saline solution (NaCl 9‰). Chronic ethanol administration intensified lipid peroxidation monitored by an increase of TBARS level in liver. Ethanol treatment caused also a drastic alteration in antioxidant defence system; hepatic superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. A co-administration of CPH during ethanol treatment inhibited lipid peroxidation and improved antioxidants activities. However, treatment with P. harmala extract protects efficiently the hepatic function of alcoholic rats by the considerable decrease of aminotransferase contents in serum of ethanol-treated rats. PMID:25974007

  14. Cyanamide Potentiates the Ethanol-Induced Impairment of Receptor-Mediated Endocytosis in a Recombinant Hepatic Cell Line Expressing Alcohol Dehydrogenase Activity

    PubMed Central

    Clemens, Dahn L.; Tuma, Dean J.; Casey, Carol A.

    2012-01-01

    Ethanol administration has been shown to alter receptor-mediated endocytosis in the liver. We have developed a recombinant hepatic cell line stably transfected with murine alcohol dehydrogenase cDNA to serve as an in vitro model to investigate these ethanol-induced impairments. In the present study, transfected cells were maintained in the absence or presence of 25?mM ethanol for 7 days, and alterations in endocytosis by the asialoglycoprotein receptor were determined. The role of acetaldehyde in this dysfunction was also examined by inclusion of the aldehyde dehydrogenase inhibitor, cyanamide. Our results showed that ethanol metabolism impaired internalization of asialoorosomucoid, a ligand for the asialoglycoprotein receptor. The addition of cyanamide potentiated the ethanol-induced defect in internalization and also impaired degradation of the ligand in the presence of ethanol. These results indicate that the ethanol-induced impairment in endocytosis is exacerbated by the inhibition of aldehyde dehydrogenase, suggesting the involvement of acetaldehyde in this dysfunction. PMID:22518324

  15. Protective effect of HO-1 transfection against ethanol-induced osteoblast damage.

    PubMed

    Li, Jie; Zhang, Feng-Quan; Du, Zhen-Ning; Cai, Teng; Cai, Peng-Shan; Fan, Lei

    2015-06-01

    Heme oxygenase-1 (HO-1) plays important roles in anti-oxidant, anti-inflammatory and immunoregulative activities. The aim of this study was to observe if HO-1 transfection could inhibit the damage of osteoblasts induced by ethanol. HO-1 was transfected into osteoblasts via constructed plasmid. After exposure to ethanol for 24 h, cytoactivity and apoptosis of osteoblasts were measured by MTT assay and flow cytometry, respectively. Furthermore, the oxidative stress and inflammatory factors in osteoblasts were measured. Compared to positive control group, the cytoactivity of transfected osteoblasts was significantly increased, and the apoptosis rate was significantly decreased (P<0.05). At the same time, the levels of reactive oxygen species (ROS), methane dicarboxylic aldehyde (MDA), tumor necrosis factor-? (TNF-?) and interleukin-1 (IL-1) were significantly decreased (P<0.05), and superoxide dismutase (SOD) level was increased (P<0.05) in the transfected osteoblasts as compared with positive controls. These results suggest that HO-1 plays a protective role in osteoblasts, and HO-1 transfection can effectively inhibit bone damage induced by ethanol. PMID:26072076

  16. Taurine: Protective properties against ethanol-induced hepatic steatosis and lipid peroxidation during chronic ethanol consumption in rats

    Microsoft Academic Search

    M. D. J. Kerai; Catherine J. Waterfield; S. H. Kenyon; D. S. Asker; J. A. Timbrell

    1998-01-01

    Summary Alcohol was administered chronically to female Sprague Dawley rats in a nutritionally adequate totally liquid diet for 28 days. This resulted in hepatic steatosis and lipid peroxidation. Taurine, when co-administered with alcohol, reduced the hepatic steatosis and completely prevented lipid peroxidation. The protective properties of taurine in preventing fatty liver were also demonstrated histologically. Although alcohol was found not

  17. Carbon monoxide alleviates ethanol-induced oxidative damage and inflammatory stress through activating p38 MAPK pathway.

    PubMed

    Li, Yanyan; Gao, Chao; Shi, Yanru; Tang, Yuhan; Liu, Liang; Xiong, Ting; Du, Min; Xing, Mingyou; Liu, Liegang; Yao, Ping

    2013-11-15

    Stress-inducible protein heme oxygenase-1(HO-1) is well-appreciative to counteract oxidative damage and inflammatory stress involving the pathogenesis of alcoholic liver diseases (ALD). The potential role and signaling pathways of HO-1 metabolite carbon monoxide (CO), however, still remained unclear. To explore the precise mechanisms, ethanol-dosed adult male Balb/c mice (5.0g/kg.bw.) or ethanol-incubated primary rat hepatocytes (100mmol/L) were pretreated by tricarbonyldichlororuthenium (II) dimmer (CORM-2, 8mg/kg for mice or 20?mol/L for hepatocytes), as well as other pharmacological reagents. Our data showed that CO released from HO-1 induction by quercetin prevented ethanol-derived oxidative injury, which was abolished by CO scavenger hemoglobin. The protection was mimicked by CORM-2 with the attenuation of GSH depletion, SOD inactivation, MDA overproduction, and the leakage of AST, ALT or LDH in serum and culture medium induced by ethanol. Moreover, CORM-2 injection or incubation stimulated p38 phosphorylation and suppressed abnormal Tnfa and IL-6, accompanying the alleviation of redox imbalance induced by ethanol and aggravated by inflammatory factors. The protective role of CORM-2 was abolished by SB203580 (p38 inhibitor) but not by PD98059 (ERK inhibitor) or SP600125 (JNK inhibitor). Thus, HO-1 released CO prevented ethanol-elicited hepatic oxidative damage and inflammatory stress through activating p38 MAPK pathway, suggesting a potential therapeutic role of gaseous signal molecule on ALD induced by naturally occurring phytochemicals. PMID:23994557

  18. Insulin Protects against Hepatic Damage Postburn

    PubMed Central

    Jeschke, Marc G; Kraft, Robert; Song, Juquan; Gauglitz, Gerd G; Cox, Robert A; Brooks, Natasha C; Finnerty, Celeste C; Kulp, Gabriela A; Herndon, David N; Boehning, Darren

    2011-01-01

    Burn injury causes hepatic dysfunction associated with endoplasmic reticulum (ER) stress and induction of the unfolded protein response (UPR). ER stress/UPR leads to hepatic apoptosis and activation of the Jun-N-terminal kinase (JNK) signaling pathway, leading to vast metabolic alterations. Insulin has been shown to attenuate hepatic damage and to improve liver function. We therefore hypothesized that insulin administration exerts its effects by attenuating postburn hepatic ER stress and subsequent apoptosis. Male Sprague Dawley rats received a 60% total body surface area (TBSA) burn injury. Animals were randomized to receive saline (controls) or insulin (2.5 IU/kg q. 24 h) and euthanized at 24 and 48 h postburn. Burn injury induced dramatic changes in liver structure and function, including induction of the ER stress response, mitochondrial dysfunction, hepatocyte apoptosis, and up-regulation of inflammatory mediators. Insulin decreased hepatocyte caspase-3 activation and apoptosis significantly at 24 and 48 h postburn. Furthermore, insulin administration decreased ER stress significantly and reversed structural and functional changes in hepatocyte mitochondria. Finally, insulin attenuated the expression of inflammatory mediators IL-6, MCP-1, and CINC-1. Insulin alleviates burn-induced ER stress, hepatocyte apoptosis, mitochondrial abnormalities, and inflammation leading to improved hepatic structure and function significantly. These results support the use of insulin therapy after traumatic injury to improve patient outcomes. PMID:21267509

  19. Effects of N-acetylcysteine on ethanol-induced hepatotoxicity in rats fed via total enteral nutrition

    PubMed Central

    Ronis, Martin J.J.; Butura, Angelica; Sampey, Brante P.; Shankar, Kartik; Prior, Ronald L.; Korourian, Sohelia; Albano, Emanuele; Ingelman-Sundberg, Magnus; Petersen, Dennis R.; Badger, Thomas M.

    2010-01-01

    The effects of the dietary antioxidant N-acetylcysteine (NAC) on alcoholic liver damage were examined in a total enteral nutrition (TEN) model of ethanol toxicity in which liver pathology occurs in the absence of endotoxemia. Ethanol treatment resulted in steatosis, inflammatory infiltrates, occasional foci of necrosis, and elevated ALT in the absence of increased expression of the endotoxin receptor CD14, a marker of Kupffer cell activation by LPS. In addition, ethanol treatment induced CYP2E1 and increased TNF? and TGF? mRNA expression accompanied by suppressed hepatic IL-4 mRNA expression. Ethanol treatment also resulted in the hepatic accumulation of malondialdehyde (MDA) and hydroxynonenal (HNE) protein adducts, decreased antioxidant capacity, and increased antibody titers toward serum hydroxyethyl radical (HER), MDA, and HNE adducts. NAC treatment increased cytosolic antioxidant capacity, abolished ethanol-induced lipid peroxidation, and inhibited the formation of antibodies toward HNE and HER adducts without interfering with CYP2E1 induction. NAC also decreased ethanol-induced ALT release and inflammation and prevented significant loss of hepatic GSH content. However, the improvement in necrosis score and reduction of TNF? mRNA elevation did not reach statistical significance. Although a direct correlation was observed among hepatic MDA and HNE adduct content and TNF? mRNA expression, inflammation, and necrosis scores, no correlation was observed between oxidative stress markers or TNF? and steatosis score. These data suggest that ethanol-induced oxidative stress can contribute to inflammation and liver injury even in the absence of Kupffer cell activation by endotoxemia. PMID:16085180

  20. An opium alkaloid-papaverine ameliorates ethanol-induced hepatotoxicity: Diminution of oxidative stress

    Microsoft Academic Search

    Ramesh Chandra; Ritu Aneja; Charu Rewal; Rama Konduri; Sujaka K. Dass; Shefali Agarwal

    2000-01-01

    In this communication, we show the modulatory potential of papaverine, an opium alkaloid and a well known vasodilator agent\\u000a on the ethanol-induced hepatic oxidative stress in male Wistar rats. Ethanol treatment (50% v\\/v) enhanced lipid peroxidation\\u000a significantly accompanied by a decline in the activities of glutathione peroxidase (G-Px), glutathione reductase (GR) and\\u000a depletion in levels of hepatic glutathione (GSH). Ethanol

  1. Specific Conditions for Resveratrol Neuroprotection against Ethanol-Induced Toxicity

    PubMed Central

    Gonthier, Brigitte; Allibe, Nathalie; Cottet-Rousselle, Cécile; Lamarche, Frédéric; Nuiry, Laurence; Barret, Luc

    2012-01-01

    Aims. 3,5,4?-Trihydroxy-trans-stilbene, a natural polyphenolic compound present in wine and grapes and better known as resveratrol, has free radical scavenging properties and is a potent protector against oxidative stress induced by alcohol metabolism. Today, the mechanism by which ethanol exerts its toxicity is still not well understood, but it is generally considered that free radical generation plays an important role in the appearance of structural and functional alterations in cells. The aim of this study was to evaluate the protective action of resveratrol against ethanol-induced brain cell injury. Methods. Primary cultures of rat astrocytes were exposed to ethanol, with or without a pretreatment with resveratrol. We examined the dose-dependent effects of this resveratrol pretreatment on cytotoxicity and genotoxicity induced by ethanol. Cytotoxicity was assessed using the MTT reduction test. Genotoxicity was evidenced using single cell gel electrophoresis. In addition, DNA staining with fluorescent dyes allowed visualization of nuclear damage using confocal microscopy. Results. Cell pretreatment with low concentrations of trans-resveratrol (0.1–10??M) slowed down cell death and DNA damage induced by ethanol exposure, while higher concentrations (50–100??M) enhanced these same effects. No protection by cis-resveratrol was observed. Conclusion. Protection offered by trans-resveratrol against ethanol-induced neurotoxicity was only effective for low concentrations of this polyphenol. PMID:22778731

  2. Quercetin prevents ethanol-induced iron overload by regulating hepcidin through the BMP6/SMAD4 signaling pathway.

    PubMed

    Tang, Yuhan; Li, Yanyan; Yu, Haiyan; Gao, Chao; Liu, Liang; Chen, Shaodan; Xing, Mingyou; Liu, Liegang; Yao, Ping

    2014-06-01

    Emerging evidence has demonstrated that chronic ethanol exposure induces iron overload, enhancing ethanol-mediated liver damage. The purpose of this study was to explore the effects of the naturally occurring compound quercetin on ethanol-induced iron overload and liver damage, focusing on the signaling pathway of the iron regulatory hormone hepcidin. Adult male C57BL/6J mice were pair-fed with isocaloric-Lieber De Carli diets containing ethanol (accounting for 30% of total calories) and/or carbonyl iron (0.2%) and treated with quecertin (100 mg/kg body weight) for 15 weeks. Mouse primary hepatocytes were incubated with ethanol (100 mM) and quercetin (100 ?M) for 24 h. Mice exposed to either ethanol or iron presented significant fatty infiltration and iron deposition in the liver; these symptoms were exacerbated in mice cotreated with ethanol and iron. Quercetin attenuated the abnormity induced by ethanol and/or iron. Ethanol suppressed BMP6 and intranuclear SMAD4 as well as decreased hepcidin expression. These effects were partially alleviated by quercetin supplementation in mice and hepatocytes. Importantly, ethanol caused suppression of SMAD4 binding to the HAMP promoter and of hepcidin messenger RNA expression. These effects were exacerbated by anti-BMP6 antibody and partially alleviated by quercetin or human recombinant BMP6 in cultured hepatocytes. In contrast, co-treatment with iron and ethanol, especially exposure of iron alone, activated BMP6/SMAD4 pathway and up-regulated hepcidin expression, which was also normalized by quercetin in vivo. Quercetin prevented ethanol-induced hepatic iron overload different from what carbonyl iron diet elicited in the mechanism, by regulating hepcidin expression via the BMP6/SMAD4 signaling pathway. PMID:24746831

  3. Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice

    SciTech Connect

    Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn; Huang, Huimin; Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn; Fan, Ting; Mu, Qingli; Li, Huani

    2013-10-01

    Excessive alcohol consumption can lead to gastric ulcer and the present work was aimed to examine the protective effect of tetrahydrocoptisine (THC) in the model of ethanol-induced gastric ulcer in mice. Fasted mice treated with ethanol 75% (0.5 ml/100 g) were pre-treated with THC (10 or 20 mg/kg, ip), cimetidine (100 mg/kg, ip) or saline in different experimental sets for a period of 3 days, and animals were euthanized 4 h after ethanol ingestion. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that ethanol induced gastric damage, improving nitric oxide (NO) level, increased pro-inflammatory cytokine (TNF-? and IL-6) levels and myeloperoxidase (MPO) activity, as well as the expression of nuclear factor-?B (NF-?B) in the ethanol group. Pretreatment of THC at doses of 10 and 20 mg/kg bodyweight significantly attenuated the gastric lesions as compared to the ethanol group. These results suggest that the gastroprotective activity of THC is attributed to reducing NO production and adjusting the pro-inflammatory cytokine, inhibited neutrophil accumulation and NF-?B expression. - Highlights: • THC decreased ethanol-induced pro-inflammatory cytokine release. • THC inhibited the production of NO in serum and gastric tissue. • THC reduced NF-?B expression and MPO accumulation in ethanol-induced gastric tissue.

  4. Hepatic damage in biliary-obstructed rats is ameliorated by leflunomide treatment

    Microsoft Academic Search

    Abdurrahman Karaman; Mustafa Iraz; Hale Kirimlioglu; Nese Karadag; Erkan Tas; Ersin Fadillioglu

    2006-01-01

    Cholestasis, or impaired bile flow, occurs in a wide variety of liver diseases and causes hepatic damage by retention and accumulation of toxic hydrophobic bile salts inducing persistent inflammation and oxidative stress. In the present research, we studied the effect of leflunomide, a novel immunosuppressive and anti-inflammatory agent against autoimmune disease, on hepatic damage produced by double ligature of the

  5. Diosmin protects against ethanol-induced gastric injury in rats: novel anti-ulcer actions.

    PubMed

    Arab, Hany H; Salama, Samir A; Omar, Hany A; Arafa, El-Shaimaa A; Maghrabi, Ibrahim A

    2015-01-01

    Alcohol consumption has been commonly associated with gastric mucosal lesions including gastric ulcer. Diosmin (DIO) is a natural citrus flavone with remarkable antioxidant and anti-inflammatory features that underlay its protection against cardiac, hepatic and renal injuries. However, its impact on gastric ulcer has not yet been elucidated. Thus, the current study aimed to investigate the potential protective effects of DIO against ethanol-induced gastric injury in rats. Pretreatment with DIO (100 mg/kg p.o.) attenuated the severity of ethanol gastric mucosal damage as evidenced by lowering of ulcer index (UI) scores, area of gastric lesions, histopathologic aberrations and leukocyte invasion. These actions were analogous to those exerted by the reference antiulcer sucralfate. DIO suppressed gastric inflammation by curbing of myeloperoxidase (MPO) and tumor necrosis factor-? (TNF-?) levels along with nuclear factor kappa B (NF-?B) p65 expression. It also augmented the anti-inflammatory interleukin-10 (IL-10) levels. Meanwhile, DIO halted gastric oxidative stress via inhibition of lipid peroxides with concomitant enhancement of glutathione (GSH), glutathione peroxidase (GPx) and the total antioxidant capacity (TAC). With respect to gastric mucosal apoptosis, DIO suppressed caspase-3 activity and cytochrome C (Cyt C) with enhancement of the anti-apoptotic B cell lymphoma-2 (Bcl-2) in favor of cell survival. These favorable actions were associated with upregulation of the gastric cytoprotective prostaglandin E2 (PGE2) and nitric oxide (NO). Together, these findings accentuate the gastroprotective actions of DIO in ethanol gastric injury which were mediated via concerted multi-pronged actions, including suppression of gastric inflammation, oxidative stress and apoptosis besides boosting of the antioxidant and the cytoprotective defenses. PMID:25821971

  6. EFFECTS OF N-ACETYLCYSTEINE ON ETHANOL-INDUCED HEPATOTOXICITY IN RATS FED VIA TOTAL ENTERAL NUTRITION.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It has been suggested that oxidative stress plays a role in the development of alcoholic liver damage but it remains unclear how important that role is and what the relationship is between oxidative stress, ethanol-induced increases in endotoxin derived from increased gut permeability to bacteria; c...

  7. Effects of Centella asiatica on ethanol induced gastric mucosal lesions in rats.

    PubMed

    Cheng, C L; Koo, M W

    2000-10-13

    Centella asiatica is a herbal medicine widely used in China and India for wound healing. The aim of this study was to examine its effects on the prevention of ethanol induced gastric lesions in rats. Gastric transmucosal potential difference (PD) was reduced by the application of 50% ethanol in the gastric ex-vivo chamber model and Centella extract (CE) accelerated its recovery. Oral administration of CE (0.05 g/kg, 0.25 g/kg and 0.50 g/kg) before ethanol administration significantly inhibited gastric lesions formation (58% to 82% reduction) and decreased mucosal myeloperoxidase (MPO) activity in a dose dependent manner. These results suggested that CE prevented ethanol induced gastric mucosal lesions by strengthening the mucosal barrier and reducing the damaging effects of free radicals. PMID:11104366

  8. Beneficial effects of Foeniculum vulgare on ethanol-induced acute gastric mucosal injury in rats

    PubMed Central

    Birdane, Fatih Mehmet; Cemek, Mustafa; Birdane, Yavuz Osman; Gülçin, ?lhami; Büyükokuro?lu, Mehmet Emin

    2007-01-01

    AIM: To examine the anti-ulcerogenic and antioxidant effects of aqueous extracts of Foeniculum vulgare (FVE) on ethanol-induced gastric lesions in rats. METHODS: FVE was administered by gavage at doses of 75, 150 and 300 mg/kg, and famotidine was used at the dose of 20 mg/kg. Following a 60 min period, all the rats were given 1 mL of ethanol (80%) by gavage. One hour after the administration of ethanol, all groups were sacrificed, and the gastric ulcer index was calculated; whole blood malondialdehyde (MDA) and reduced glutathione (GSH), serum nitrate, nitrite, ascorbic acid, retinol and ?-carotene levels were measured in all the groups. RESULTS: It was found that pretreatment with FVE significantly reduced ethanol-induced gastric damage. This effect of FVE was highest and statistically significant in 300 mg/kg group compared with the control (4.18 ± 2.81 vs 13.15 ± 4.08, P < 0.001). Also, pretreatment with FVE significantly reduced the MDA levels, while significantly increased GSH, nitrite, nitrate, ascorbic acid, retinol and ?-carotene levels. CONCLUSION: FVE has clearly a protective effect against ethanol-induced gastric mucosal lesion, and this effect, at least in part, depends upon the reduction in lipid peroxidation and augmentation in the antioxidant activity. PMID:17278229

  9. p53-Mediated Cellular Response to DNA Damage in Cells with Replicative Hepatitis B Virus

    NASA Astrophysics Data System (ADS)

    Puisieux, Alain; Ji, Jingwei; Guillot, Celine; Legros, Yann; Soussi, Thierry; Isselbacher, Kurt; Ozturk, Mehmet

    1995-02-01

    Wild-type p53 acts as a tumor suppressor gene by protecting cells from deleterious effects of genotoxic agents through the induction of a G_1/S arrest or apoptosis as a response to DNA damage. Transforming proteins of several oncogenic DNA viruses inactivate tumor suppressor activity of p53 by blocking this cellular response. To test whether hepatitis B virus displays a similar effect, we studied the p53-mediated cellular response to DNA damage in 2215 hepatoma cells with replicative hepatitis B virus. We demonstrate that hepatitis B virus replication does not interfere with known cellular functions of p53 protein.

  10. Protective Effects of the Traditional Herbal Formula Oryeongsan Water Extract on Ethanol-Induced Acute Gastric Mucosal Injury in Rats

    PubMed Central

    Jeon, Woo-Young; Lee, Mee-Young; Shin, In-Sik; Lim, Hye-Sun; Shin, Hyeun-Kyoo

    2012-01-01

    This study was performed to evaluate the protective effect and safety of Oryeongsan water extract (OSWE) on ethanol-induced acute gastric mucosal injury and an acute toxicity study in rats. Acute gastric lesions were induced via intragastric oral administration of absolute ethanol at a dose of 5?mL/kg. OSWE (100 and 200?mg/kg) was administered to rats 2?h prior to the oral administration of absolute ethanol. The stomach of animal models was opened and gastric mucosal lesions were examined. Gastric mucosal injuries were evaluated by measuring the levels of malondialdehyde (MDA), glutathione (GSH), and the activity of antioxidant enzymes. In the acute toxicity study, no adverse effects of OSWE were observed at doses up to 2000?mg/kg/day. Administration of OSWE reduced the damage by conditioning the gastric mucosa against ethanol-induced acute gastric injury, which included hemorrhage, hyperemia, and loss of epithelial cells. The level of MDA was reduced in OSWE-treated groups compared with the ethanol-induced group. Moreover, the level of GSH and the activity of antioxidant enzymes were significantly increased in the OSWE-treated groups. Our findings suggest that OSWE has a protective effect on the gastric mucosa against ethanol-induced acute gastric injury via the upregulation of antioxidant enzymes. PMID:23118790

  11. Ethanol induced impairment of glucose metabolism involves alterations of GABAergic signaling in pancreatic ?-cells.

    PubMed

    Wang, Shuanglian; Luo, Yan; Feng, Allen; Li, Tao; Yang, Xupeng; Nofech-Mozes, Roy; Yu, Meng; Wang, Changhui; Li, Ziwei; Yi, Fan; Liu, Chuanyong; Lu, Wei-Yang

    2014-12-01

    Alcohol overindulgence is a risk factor of type 2 diabetes mellitus. However, the mechanisms by which alcohol overindulgence damages glucose metabolism remain unclear. Pancreatic islet ?-cells are endowed with type-A ?-aminobutyric acid receptor (GABAAR) mediated autocrine signaling mechanism, which regulates insulin secretion and fine-tunes glucose metabolism. In neurons GABAAR is one of the major targets for alcohol. This study investigated whether ethanol alters glucose metabolism by affecting GABAAR signaling in pancreatic ?-cells. Blood glucose level of test mice was measured using a blood glucose meter. Insulin secretion by the pancreatic ?-cell line INS-1 cells was examined using a specific insulin ELISA kit. Whole-cell patch-clamp recording was used to evaluate GABA-elicited current in INS-1 cells. Western blot and immunostaining were used to measure the expression of GABAAR subunits in mouse pancreatic tissues or in INS-1 cells. Intraperitoneal (i.p.) administration of ethanol (3.0g/kg body weight) to mice altered glucose metabolism, which was associated with decreased expression of GABAAR ?1- and ?- subunits on the surface of pancreatic ?-cells. Acute treatment of cultured INS-1cells with ethanol (60mM) decreased the GABA-induced current and reduced insulin secretion. In contrast, treating INS-1 cells with GABA (100?M) largely prevented the ethanol-induced reduction of insulin release. Importantly, pre-treating mice with GABA (i.p., 1.5mg/kg body weight) partially reversed ethanol-induced impairment of glucose homeostasis in mice. Our data suggest a novel role of pancreatic GABA signaling in protecting pancreatic islet ?-cells from ethanol-induced dysfunction. PMID:25456265

  12. Hepatitis B

    MedlinePLUS

    ... of the hepatitis B virus. This is called chronic hepatitis B. People with chronic hepatitis may not have symptoms ... to look for liver damage if you have chronic hepatitis B: Albumin level Liver function tests Prothrombin time You ...

  13. Preventive effects of geranylgeranylacetone on rat ethanol-induced gastritis

    PubMed Central

    Ning, Jian-Wen; Lin, Guan-Bin; Ji, Feng; Xu, Jia; Sharify, Najeeb

    2012-01-01

    AIM: To establish a rat ethanol gastritis model, we evaluated the effects of ethanol on gastric mucosa and studied the preventive effects of geranylgeranylacetone on ethanol-induced chronic gastritis. METHODS: One hundred male Sprague-Dawley rats were randomly divided into 4 equal groups: normal control group, undergoing gastric perfusion of normal saline (NS) by gastrogavage; model control group and 2 model therapy groups that underwent gastric perfusion with ethanol (distillate spirits with 56% ethanol content) by gastrogavage for 4 wk. Low or high doses of geranylgeranylacetone were added 1 h before ethanol perfusion in the 2 model therapy groups, while the same amount of NS, instead of geranylgeranylacetone was used in that model control group. The rats were then sacrificed and stomachs were removed. The injury level of the gastric mucosa was observed by light and electron microscopy, and the levels of prostaglandin 2 (PGE2), endothelin-1 (ET-1) and nitric oxide (NO) were measured by radioimmunoassay and the Griess method. RESULTS: The gastric mucosal epidermal damage score (EDS; 4.5) and ulcer index (UI; 12.0) of the model control group were significantly higher than that of the normal control group (0 and 0 respectively, all P = 0.000). The gastric mucosal EDS and UI of the 2 model therapy groups (EDS: 2.5 and 2.0; UI: 3.5 and 3.0) were significantly lower than that of the model control group (all P < 0.01). There was no statistically significant difference between the low-dose and high-dose model therapy groups. The expression value of plasma ET-1 of the model control group was higher than that of the normal control group (P < 0.01) and the 2 model therapy groups (all P < 0.01). The expression values of gastric mucosal PGE2 and serum NO of the model control group were lower than those of the normal control group (all P < 0.05) and the 2 model therapy groups (all P < 0.05). The thickness of the gastric mucous layerand the hexosamine content in the model control group were significantly lower than that in the normal control group (all P < 0.01) and the 2 model therapy groups (all P < 0.05). Scanning and transmission electron microscopy observation showed that in the model control group, the epithelial junctions were vague, the intercellular joints disappeared and damage of the intracellular organelles were significantly worse than those in the normal control group. However, in the 2 model therapy groups, damage to the intercellular joints and organelles was ameliorate relative to the model control group. CONCLUSION: Administration of geranylgeranylacetone was correlated with a more favorable pattern of gastric mucosa damage after ethanol perfusion. The mechanism could be related to regulation of ET-1, NO and PGE2. PMID:22611321

  14. Ischemic and non-ischemic acute kidney injury cause hepatic damage

    Microsoft Academic Search

    Fereshteh Golab; Mehri Kadkhodaee; Maryam Zahmatkesh; Mehdi Hedayati; Hossein Arab; Rebecca Schuster; Kamyar Zahedi; Alex B Lentsch; Manoocher Soleimani

    2009-01-01

    Recent studies have documented that remote organs are affected by ischemic injury to the kidney. Here we studied whether the liver also suffers damage during induction of renal ischemia–reperfusion in rats and compared this to bilateral nephrectomy. Hepatic levels of tumor necrosis factor-? increased significantly after 6 and 24 h of renal ischemia or nephrectomy. Malondialdehyde, an index of lipid

  15. Hepatoprotective Activity of Bi-Herbal Ethanolic Extract on CCl4 Induced Hepatic Damage in Rats

    Microsoft Academic Search

    P. Samudram; Rajeshwari Hari; R. Vasuki; A. Geetha; P. Sathiya Moorthi

    2008-01-01

    The combined hepatoprotective effect of Bi- herbal ethanolic extract (BHEE) was evaluated against carbon tetra chloride (CCl4) induced hepatic damage in rats. Ethanolic extract from the leaves of Eclipta alba and seeds of Piper longum at a dose level of 50 mg\\/kg body weight was administered orally daily once for 14 days. The substantially elevated serum marker enzymes such as

  16. On the mechanism underlying ethanol-induced mitochondrial dynamic disruption and autophagy response.

    PubMed

    Bonet-Ponce, Luis; Saez-Atienzar, Sara; da Casa, Carmen; Flores-Bellver, Miguel; Barcia, Jorge M; Sancho-Pelluz, Javier; Romero, Francisco J; Jordan, Joaquín; Galindo, María F

    2015-07-01

    We have explored the mechanisms underlying ethanol-induced mitochondrial dynamics disruption and mitophagy. Ethanol increases mitochondrial fission in a concentration-dependent manner through Drp1 mitochondrial translocation and OPA1 proteolytic cleavage. ARPE-19 (a human retinal pigment epithelial cell line) cells challenged with ethanol showed mitochondrial potential disruptions mediated by alterations in mitochondrial complex IV protein level and increases in mitochondrial reactive oxygen species production. In addition, ethanol activated the canonical autophagic pathway, as denoted by autophagosome formation and autophagy regulator elements including Beclin1, ATG5-ATG12 and P-S6 kinase. Likewise, autophagy inhibition dramatically increased mitochondrial fission and cell death, whereas autophagy stimulation rendered the opposite results, placing autophagy as a cytoprotective response aimed to remove damaged mitochondria. Interestingly, although ethanol induced mitochondrial Bax translocation, this episode was associated to cell death rather than mitochondrial fission or autophagy responses. Thus, Bax required 600mM ethanol to migrate to mitochondria, a concentration that resulted in cell death. Furthermore, mouse embryonic fibroblasts lacking this protein respond to ethanol by undergoing mitochondrial fission and autophagy but not cytotoxicity. Finally, by using the specific mitochondrial-targeted scavenger MitoQ, we revealed mitochondria as the main source of reactive oxygen species that trigger autophagy activation. These findings suggest that cells respond to ethanol activating mitochondrial fission machinery by Drp1 and OPA1 rather than bax, in a manner that stimulates cytoprotective autophagy through mitochondrial ROS. PMID:25779081

  17. Ethanol-Induced Cerebellar Ataxia: Cellular and Molecular Mechanisms.

    PubMed

    Dar, M Saeed

    2015-08-01

    The cerebellum is an important target of ethanol toxicity given that cerebellar ataxia is the most consistent physical manifestation of acute ethanol consumption. Despite the significance of the cerebellum in ethanol-induced cerebellar ataxia (EICA), the cellular and molecular mechanisms underlying EICA are incompletely understood. However, two important findings have shed greater light on this phenomenon. First, ethanol-induced blockade of cerebellar adenosine uptake in rodent models points to a role for adenosinergic A1 modulation of EICA. Second, the consistent observation that intracerebellar administration of nicotine in mice leads to antagonism of EICA provides evidence for a critical role of cerebellar nitric oxide (NO) in EICA reversal. Based on these two important findings, this review discusses the potential molecular events at two key synaptic sites (mossy fiber-granule cell-Golgi cell (MGG synaptic site) and granule cell parallel fiber-Purkinje cell (GPP synaptic site) that lead to EICA. Specifically, ethanol-induced neuronal NOS inhibition at the MGG synaptic site acts as a critical trigger for Golgi cell activation which leads to granule cell deafferentation. Concurrently, ethanol-induced inhibition of adenosine uptake at the GPP synaptic site produces adenosine accumulation which decreases glutamate release and leads to the profound activation of Purkinje cells (PCs). These molecular events at the MGG and GPP synaptic sites are mutually reinforcing and lead to cerebellar dysfunction, decreased excitatory output of deep cerebellar nuclei, and EICA. The critical importance of PCs as the sole output of the cerebellar cortex suggests normalization of PC function could have important therapeutic implications. PMID:25578036

  18. Metadoxine prevents damage produced by ethanol and acetaldehyde in hepatocyte and hepatic stellate cells in culture.

    PubMed

    Gutiérrez-Ruiz, M C; Bucio, L; Correa, A; Souza, V; Hernández, E; Gómez-Quiroz, L E; Kershenobich, D

    2001-11-01

    Metadoxine (pyridoxine-pyrrolidone carboxylate) has been reported to improve liver function tests in alcoholic patients. In the present work we have investigated the effect of metadoxine on some parameters of cellular damage in hepatocytes and hepatic stellate cells in culture treated with ethanol and acetaldehyde. HepG2 and CFSC-2G cells were treated with 50 mM ethanol or 175 microM acetaldehyde as initial concentration in the presence or absence of 10 microg ml(-1) of metadoxine. Twenty-four hours later reduced and oxidized glutathione content, lipid peroxidation damage, collagen secretion and IL-6, IL-8 and TNF- alpha secretion were determined. Our results suggest that metadoxine prevents glutathione depletion and the increase in lipid peroxidation damage caused by ethanol and acetaldehyde in HepG2 cells. In hepatic stellate cells, metadoxine prevents the increase in collagen and attenuated TNF- alpha secretion caused by acetaldehyde. Thus, metadoxine could be useful in preventing the damage produced in early stages of alcoholic liver disease as it prevents the redox imbalance of the hepatocytes and prevents TNF- alpha induction, one of the earliest events in hepatic damage. PMID:11712874

  19. Adenosine signaling contributes to ethanol-induced fatty liver in mice

    PubMed Central

    Peng, Zhongsheng; Borea, Pier Andrea; Wilder, Tuere; Yee, Herman; Chiriboga, Luis; Blackburn, Michael R.; Azzena, Gianfranco; Resta, Giuseppe; Cronstein, Bruce N.

    2009-01-01

    Fatty liver is commonly associated with alcohol ingestion and abuse. While the molecular pathogenesis of these fatty changes is well understood, the biochemical and pharmacological mechanisms by which ethanol stimulates these molecular changes remain unknown. During ethanol metabolism, adenosine is generated by the enzyme ecto-5?-nucleotidase, and adenosine production and adenosine receptor activation are known to play critical roles in the development of hepatic fibrosis. We therefore investigated whether adenosine and its receptors play a role in the development of alcohol-induced fatty liver. WT mice fed ethanol on the Lieber-DeCarli diet developed hepatic steatosis, including increased hepatic triglyceride content, while mice lacking ecto-5?-nucleotidase or adenosine A1 or A2B receptors were protected from developing fatty liver. Similar protection was also seen in WT mice treated with either an adenosine A1 or A2B receptor antagonist. Steatotic livers demonstrated increased expression of genes involved in fatty acid synthesis, which was prevented by blockade of adenosine A1 receptors, and decreased expression of genes involved in fatty acid metabolism, which was prevented by blockade of adenosine A2B receptors. In vitro studies supported roles for adenosine A1 receptors in promoting fatty acid synthesis and for A2B receptors in decreasing fatty acid metabolism. These results indicate that adenosine generated by ethanol metabolism plays an important role in ethanol-induced hepatic steatosis via both A1 and A2B receptors and suggest that targeting adenosine receptors may be effective in the prevention of alcohol-induced fatty liver. PMID:19221436

  20. Oxidative Damage of Fe3O4 Nanoparticles on Mouse Hepatic Cells In Vitro

    Microsoft Academic Search

    Ye Yuan; Jiaqi Tang; Chenxi Wei; Bing Han; Xu Yang

    2011-01-01

    In order to assess the biological safety of Fe3O4 nanoparticles, oxidative damage of which was studied. Mouse hepatic cells were exposed to different dose (50 ?g\\/mL, 100 ?g\\/mL, 200 ?g\\/mL, 400 ?g\\/mL) of Fe3O4 nanoparticles in vitro for 1 hour. Methods of 2, 7-dichlorohydrofluoroscein diacetate (DCFH-DA), 5, 5'-dithiobis (2-nitrobenzoic acid) (DTNB), thiobarbituric acid (TBA) were used to detect reactive oxygen

  1. Protective effect of Indigofera aspalathoides against CCl4-induced hepatic damage in rats.

    PubMed

    Rajkapoor, B; Jayakar, B; Kavimani, S; Murugesh, N

    2006-01-01

    The alcoholic extract of stem of Indigofera aspalathoides was evaluated for its antihepatotoxic activity against CCl(4)-induced hepatic damage in rats. The activity was evaluated by using biochemical parameters, such as serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), total bilirubin and gama glutamate transpeptidase (GGTP). The histopathological changes of liver sample were compared with respective control. The extract showed remarkable hepatoprotective effect. PMID:17135160

  2. Ethanol induces rotational behavior in 6-hydroxydopamine lesioned mice

    SciTech Connect

    Silverman, P.B.

    1987-03-09

    Mice with unilateal striatal lesions created by 6-hydroxydopamine (6HDA) injection were screened for rotational (circling) behavior in response to injection of amphetamine and apomorphine. Those that rotated ipsilaterally in response to amphetamine and contralaterally in response to apomorphine were subsequently challenged with 1 to 3 g/kg (i.p.) ethanol. Surprisingly, ethanol induced dose related contralateral (apomorphine-like) rotation which, despite gross intoxication, was quite marked in most animals. No significant correlation was found between the number of turns made following ethanol and made after apomorphine or amphetamine. 14 references, 2 figures, 1 table.

  3. Herbal SGR Formula Prevents Acute Ethanol-Induced Liver Steatosis via Inhibition of Lipogenesis and Enhancement Fatty Acid Oxidation in Mice

    PubMed Central

    Qiu, Ping; Li, Xiang; Kong, De-song; Li, Huan-zhou; Niu, Cong-cong; Pan, Su-hua

    2015-01-01

    Our previous study indicated that herbal SGR formula partially attenuates ethanol-induced fatty liver, but the underlying mechanisms remain unclear. In the present study, mice were pretreated with SGR (100 and 200?mg/kg/d?bw) for 30?d before being exposed to ethanol (4.8?g/kg?bw). The biochemical indices and histopathological changes were examined to evaluate the protective effects and to explore potential mechanisms by investigating the adiponectin, tumor necrosis factor-? (TNF-?), peroxisome proliferators-activated receptor-? (PPAR-?), sterol regulatory element binding protein-1c (SREBP-1c), adenosine monophosphate-activated protein kinase (AMPK), and so forth. Results showed that SGR pretreatment markedly inhibited acute ethanol-induced liver steatosis, significantly reduced serum and hepatic triglyceride (TG) level, and improved classic histopathological changes. SGR suppressed the protein expression of hepatic SREBP-1c and TNF-? and increased adiponectin, PPAR-?, and AMPK phosphorylation in the liver. Meanwhile, acute toxicity tests showed that no death or toxic side effects within 14 days were observed upon oral administration of the extracts at a dose of 16?g/kg body wt. These results demonstrate that SGR could protect against acute alcohol-induced liver steatosis without any toxic side effects. Therefore, our studies provide novel molecular insights into the hepatoprotective effect of SGR formula, which may be exploited as a therapeutic agent for ethanol-induced hepatosteatosis.

  4. Hepatitis

    MedlinePLUS

    ... hepatitis B, although people who have had the hepatitis B vaccine are protected against it. In most cases, teens ... approved for use in adults. Although treatments for hepatitis B and C are becoming ... Vaccinated Vaccines can protect people against hepatitis A and hepatitis ...

  5. Hepatitis

    MedlinePLUS

    ... recommend an injection of immune (gamma) globulin. The hepatitis B vaccine is part of the recommended series of immunizations ... receive a total of 3 doses of the hepatitis B vaccine. Although there is no vaccine specifically for hepatitis ...

  6. Hepatitis D

    MedlinePLUS

    ... Skip Content Marketing Share this: Main Content Area Hepatitis D Hepatitis D is a viral infection that damages the liver, but it can propagate only when the hepatitis B virus is also present. Approximately 15 million ...

  7. Neuroprotection with metformin and thymoquinone against ethanol-induced apoptotic neurodegeneration in prenatal rat cortical neurons

    PubMed Central

    2012-01-01

    Background Exposure to ethanol during early development triggers severe neuronal death by activating multiple stress pathways and causes neurological disorders, such as fetal alcohol effects or fetal alcohol syndrome. This study investigated the effect of ethanol on intracellular events that predispose developing neurons for apoptosis via calcium-mediated signaling. Although the underlying molecular mechanisms of ethanol neurotoxicity are not completely determined, mitochondrial dysfunction, altered calcium homeostasis and apoptosis-related proteins have been implicated in ethanol neurotoxicity. The present study was designed to evaluate the neuroprotective mechanisms of metformin (Met) and thymoquinone (TQ) during ethanol toxicity in rat prenatal cortical neurons at gestational day (GD) 17.5. Results We found that Met and TQ, separately and synergistically, increased cell viability after ethanol (100 mM) exposure for 12 hours and attenuated the elevation of cytosolic free calcium [Ca2+]c. Furthermore, Met and TQ maintained normal physiological mitochondrial transmembrane potential (??M), which is typically lowered by ethanol exposure. Increased cytosolic free [Ca2+]c and lowered mitochondrial transmembrane potential after ethanol exposure significantly decreased the expression of a key anti-apoptotic protein (Bcl-2), increased expression of Bax, and stimulated the release of cytochrome-c from mitochondria. Met and TQ treatment inhibited the apoptotic cascade by increasing Bcl-2 expression. These compounds also repressed the activation of caspase-9 and caspase-3 and reduced the cleavage of PARP-1. Morphological conformation of cell death was assessed by TUNEL, Fluoro-Jade-B, and PI staining. These staining methods demonstrated more cell death after ethanol treatment, while Met, TQ or Met plus TQ prevented ethanol-induced apoptotic cell death. Conclusion These findings suggested that Met and TQ are strong protective agents against ethanol-induced neuronal apoptosis in primary rat cortical neurons. The collective data demonstrated that Met and TQ have the potential to ameliorate ethanol neurotoxicity and revealed a possible protective target mechanism for the damaging effects of ethanol during early brain development. PMID:22260211

  8. Ameliorative effect of Opuntia ficus indica juice on ethanol-induced oxidative stress in rat erythrocytes.

    PubMed

    Alimi, Hichem; Hfaeidh, Najla; Bouoni, Zouhour; Sakly, Mohsen; Rhouma, Khémais Ben

    2013-05-01

    The aim of the present study was to investigate the efficacy of Opuntia ficus indica f. inermis fruit juice (OFIj) on reversing oxidative damages induced by chronic ethanol intake in rat erythrocytes. OFIj was firstly analyzed with HPLC for phenolic and flavonoids content. Secondly, 40 adult male Wistar rats were equally divided into five groups and treated for 90 days as follows: control (C), ethanol-only 3 g/kg body weight (b.w) (E), low dose of OFIj 2 ml/100 g b.w+ethanol (Ldj+E), high dose of OFIj 4 ml/100 g b.w+ethanol (Hdj+E), and only a high dose of OFIj 4 ml/100g b.w (Hdj). HPLC analysis indicated high concentrations of phenolic acids and flavonoids in OFIj. Ethanol treatment markedly decreased the activities of erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), and the level of reduced glutathione (GSH). Changes in the erythrocyte's antioxidant ability were accompanied by enhanced oxidative modification of lipids (increase of malondialdeyde level) and proteins (increase in carbonyl groups). Interestingly, pre-administration of either 2 ml/100 g b.w or 4 ml/100 g b.w of OFIj to ethanol-intoxicated rats significantly reversed decreases in enzymatic as well as non enzymatic antioxidants parameters in erythrocytes. Also, the administration of OFIj significantly protected lipids and proteins against ethanol-induced oxidative modifications in rat erythrocytes. The beneficial effect of OFIj can result from the inhibition of ethanol-induced free radicals chain reactions in rat erythrocytes or from the enhancement of the endogenous antioxidants activities. PMID:22285760

  9. Characterization of hepatic DNA damage induced in rats by the pyrrolizidine alkaloid monocrotaline

    SciTech Connect

    Petry, T.W.; Bowden, G.T.; Huxtable, R.J.; Sipes, I.G.

    1984-04-01

    Hepatic DNA damage induced by the pyrrolizidine alkaloid monocrotaline was evaluated following i.p. administration to adult male Sprague-Dawley rats. Animals were treated with various doses ranging upward from 5 mg/kg, and hepatic nuclei were isolated 4 hr later. Hepatic nuclei were used as the DNA source in all experiments. DNA damage was characterized by the alkaline elution technique. A mixture of DNA-DNA interstrand cross-links and DNA-protein cross-links was induced. Following an injection of monocrotaline, 30 mg/kg i.p., DNA-DNA interstrand cross-linking reached a maximum within 12 hr or less and thereafter decreased over a protracted period of time. By 96 hr postadministration, the calculated cross-linking factor was no longer statistically different from zero. No evidence for the induction of DNA single-strand breaks was observed, although the presence of small numbers of DNA single-strand breaks could have been masked by the overwhelming predominance of DNA cross-links. These DNA cross-links may be related to the hepatocarcinogenic, hepatotoxic, and/or antimitotic effects of monocrotaline.

  10. Expression of Ethanol-Induced Behavioral Sensitization Is Associated with Alteration of Chromatin Remodeling in

    E-print Network

    Boyer, Edmond

    Expression of Ethanol-Induced Behavioral Sensitization Is Associated with Alteration of Chromatin), Amiens, France Abstract Background: Ethanol-induced behavioral sensitization (EIBS) is proposed to play in the development and the persistence of ethanol-related behaviors, we explored the involvement of epigenetic

  11. Dendrobium candidum Wall. ex Lindl. attenuates CCl4-induced hepatic damage in imprinting control region mice

    PubMed Central

    LI, GUI-JIE; SUN, PENG; WANG, QIANG; QIAN, YU; ZHU, KAI; ZHAO, XIN

    2014-01-01

    The aim of the present study was to determine the preventive effect of the traditional Chinese medicine, Dendrobium candidum Wall ex Lindl. (D. candidum), on CCl4-induced hepatic damage in mice. The CCl4-induced hepatic damage mice were treated with D. candidum, and the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), triglyceride (TG) and total cholesterol (TC) were determined. In addition, serum cytokine levels of interleukin (IL)-6, IL-12, tumor necrosis factor (TNF)-? and interferon (IFN)-? were analyzed with kits, while liver tissues were analyzed using hematoxylin and eosin staining and reverse transcription polymerase chain reaction (RT-PCR). Furthermore, the contents of D. candidum were determined by nuclear magnetic resonance (NMR). D. candidum was demonstrated to successfully prevent hepatic damage in mice. The serum levels of AST, ALT and LDH were significantly decreased when the mice were treated with 200 and 400 mg/kg D. candidum, as compared with the control mice (P<0.05). The lowest enzymatic activities were exhibited in the 400 mg/kg D. candidum group, which produced similar results to the positive control drug, silymarin. In addition, in the 400 mg/kg D. candidum group, the highest levels of TG and TC were observed among the treated groups. D. candidum-treated groups also demonstrated reduced levels of the serum proinflammatory cytokines, IL-6, IL-12, TNF-? and IFN-?. The sections of liver tissue examined during histopathology in the high concentration 400 mg/kg D. candidum group recovered well from CCl4 damage; however, the sections in the 200 mg/kg D. candidum group revealed necrosis to a more serious degree. RT-PCR analysis was conducted on inflammation-associated genes, including nuclear factor (NF)-?B, I?B-?, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, in the livers of the mice. The 400 mg/kg D. candidum group demonstrated significantly decreased mRNA expression levels of NF-?B, iNOS and COX-2, but an increased expression level of I?B-? when compared with the CCl4-treated control group. Furthermore, using NMR, 11 compounds were identified in the D. candidum leaf, whose functional contents may aid the preventive effect observed in the current study. Therefore, D. candidum may potentially contribute to the prevention of CCl4-induced hepatic damage in vivo. PMID:25120640

  12. Salvia miltiorrhiza Bunge and its active component cryptotanshinone protects primary cultured rat hepatocytes from acute ethanol-induced cytotoxicity and fatty infiltration.

    PubMed

    Yin, Hu-Quan; Choi, You-Jin; Kim, Youn-Chul; Sohn, Dong-Hwan; Ryu, Shi-Yong; Lee, Byung-Hoon

    2009-01-01

    Alcoholic liver disease involves hepatocellular injury induced by the acute or chronic consumption of ethanol. Fatty infiltration is usually followed by inflammation and focal necrosis, which can lead to cirrhosis if not treated properly in the initial stage. There have been many attempts to develop effective therapies for the disease, using natural products derived from medicinal plants. In this study, we report that the standardized fraction of Salvia miltiorrhiza Bunge (Sm-SF) and its active component, cryptotanshinone, were able to protect hepatocytes from lipopolysaccharide- and ethanol-induced cell death. They also suppressed ethanol-induced lipid accumulation as evidenced by the Nile red binding assay. The ethanol-induced activation and nuclear translocation of sterol regulatory element-binding protein-1 and the consequent transactivation of the target genes involved in fatty acid biosynthesis were inhibited by Sm-SF and cryptotanshinone in a dose-dependent manner. Cryptotanshinone, an active component of S. miltiorrhiza, has the potential to ameliorate alcoholic liver disease by blocking hepatic cell death and fatty acid synthesis. PMID:19013495

  13. Salvianolic acid B protects against acute ethanol-induced liver injury through SIRT1-mediated deacetylation of p53 in rats.

    PubMed

    Li, Mingzhu; Lu, Yang; Hu, Yan; Zhai, Xiaohan; Xu, Wei; Jing, Huirong; Tian, Xiaofeng; Lin, Yuan; Gao, Dongyan; Yao, Jihong

    2014-07-15

    Salvianolic acid B (SalB) is isolated from the traditional Chinese medical herb salvia miltiorrhiza. It has many biological and pharmaceutical activities. This study aimed to investigate the effect of SalB on acute ethanol-induced hepatic injury in rats and to explore the role of SIRT1 in this process. The results showed that pretreatment with SalB significantly reduced ethanol-induced elevation in aminotransferase activities, decreased hepatotoxic cytokine levels such as Interleukin-6 (IL-6), and increased the antioxidant enzyme activity. Moreover, SalB pretreatment reversed the increase in NF-?B, cleaved caspase-3 and decrease in B-cell lymphoma-extra large (Bcl-xL) caused by ethanol exposure. Importantly, SalB pretreatment significantly increased the expression of SIRT1, a NAD(+)-dependent deacetylase, whereas the increase in SIRT1 was accompanied by decreased acetyl-p53 expression. In HepG2 cells, SalB pretreatment increased SIRT1 expression in a time and dose-dependent manner and such an increase was abrogated by siRNA knockdown of SIRT1. Additionally, inhibition of SIRT1 significantly increased the acetylation of p53, and blocked SalB-induced acetylation of p53 down-regulation. Collectively, this study indicated that SalB can alleviate acute ethanol-induced hepatocyte apoptosis through SIRT1-mediated deacetylation of p53 pathway. PMID:24769256

  14. Lycopene Pretreatment Ameliorates Acute Ethanol Induced NAD+ Depletion in Human Astroglial Cells

    PubMed Central

    Guest, Jade; Heng, Benjamin; Grant, Ross

    2015-01-01

    Excessive alcohol consumption is associated with reduced brain volume and cognition. While the mechanisms by which ethanol induces these deleterious effects in vivo are varied most are associated with increased inflammatory and oxidative processes. In order to further characterise the effect of acute ethanol exposure on oxidative damage and NAD+ levels in the brain, human U251 astroglioma cells were exposed to physiologically relevant doses of ethanol (11?mM, 22?mM, 65?mM, and 100?mM) for ? 30 minutes. Ethanol exposure resulted in a dose dependent increase in both ROS and poly(ADP-ribose) polymer production. Significant decreases in total NAD(H) and sirtuin 1 activity were also observed at concentrations ? 22?mM. Similar to U251 cells, exposure to ethanol (?22?mM) decreased levels of NAD(H) in primary human astrocytes. NAD(H) depletion in primary astrocytes was prevented by pretreatment with 1??M of lycopene for 3.5 hours. Unexpectedly, in U251 cells lycopene treatment at concentrations ? 5??M resulted in significant reductions in [NAD(H)]. This study suggests that exposure of the brain to alcohol at commonly observed blood concentrations may cause transitory oxidative damage which may be at least partly ameliorated by lycopene.

  15. Vinpocetine ameliorates acute hepatic damage caused by administration of carbon tetrachloride in rats.

    PubMed

    Abdel Salam, O M E; Oraby, Fatma Hassan; Hassan, Nabila S

    2007-12-01

    Vinpocetine is a widely used drug for the treatment of cerebrovascular and memory disorders. This study aimed to investigate the effect of vinpocetine on the acute hepatic injury caused in the rat by the administration of CCl4 in vivo. Vinpocetine (2.1, 4.2, 8.4 mg/kg) or silymarin (30 mg/kg) was given once daily orally simultaneously with CCl4 and for 15 days thereafter. Liver damage was assessed by determining serum enzyme activities and hepatic histopathology. Stained sections were subjected to morphometric evaluation using computerized image analyzer. The results showed that vinpocetine administered to CCl4-treated rats decreased the elevated alanine aminotransferase (ALT) by 49.3, 58.1 and 63.6%, aspartate aminotransferase (AST) by 10.5, 22.6 and 27.2% and alkaline phosphatase (ALP) by 52.5, 59.6 and 64.9%, respectively, and in a dose-dependent manner. Meanwhile, silymarin reduced elevated ALT, AST and ALP levels by 53.1, 26.9 and 66%, respectively. Histological examination of liver specimens revealed a marked reduction in liver cell necrosis in vinpocetine and silymarin-treated rats compared with vehicle-treated CCl4-treated rats. Quantitative analysis of the area of damage showed 85.3% reduction in the area of damage after silymarin and 72.2, 78.9 and 82.6% reduction after vinpocetine treatment at 2.1, 4.2, 8.4 mg/kg, respectively. It is concluded that administration of vinpocetine in a model of CCl4-induced liver injury in rats reduced liver damage. The reduction obtained by 4.2 mg/kg of vinpocetine was similar to that obtained by 30 mg/kg silymarin. Therefore, it is suggested that vinpocetine might be a good pharmacological agent in the treatment of liver disease besides its neuroprotective effects. PMID:18277467

  16. Hepatitis

    MedlinePLUS

    Dienstag JL. Hepatitis B virus infection. N Engl J Med . 2008;359:1486-1500. Jou JH, Muir AJ. In the clinic. Hepatitis C. Ann Intern Med . 2008;148:iTC6-1-ITC6-16. Sjogren MH, Cheatham JG. Hepatitis A. In: Feldman M, ...

  17. Strawberry Polyphenols Attenuate Ethanol-Induced Gastric Lesions in Rats by Activation of Antioxidant Enzymes and Attenuation of MDA Increase

    PubMed Central

    Alvarez-Suarez, José M.; Dekanski, Dragana; Risti?, Slavica; Radonji?, Nevena V.; Petronijevi?, Nataša D.; Giampieri, Francesca; Astolfi, Paola; González-Paramás, Ana M.; Santos-Buelga, Celestino; Tulipani, Sara; Quiles, José L.; Mezzetti, Bruno; Battino, Maurizio

    2011-01-01

    Background and Aim Free radicals are implicated in the aetiology of gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. Strawberries are common and important fruit due to their high content of essential nutrient and beneficial phytochemicals which seem to have relevant biological activity on human health. In the present study we investigated the antioxidant and protective effects of three strawberry extracts against ethanol-induced gastric mucosa damage in an experimental in vivo model and to test whether strawberry extracts affect antioxidant enzyme activities in gastric mucosa. Methods/Principal Findings Strawberry extracts were obtained from Adria, Sveva and Alba cultivars. Total antioxidant capacity and radical scavenging capacity were performed by TEAC, ORAC and electron paramagnetic resonance assays. Identification and quantification of anthocyanins was carried out by HPLC-DAD-MS analyses. Different groups of animals received 40 mg/day/kg body weight of strawberry crude extracts for 10 days. Gastric damage was induced by ethanol. The ulcer index was calculated together with the determination of catalase and SOD activities and MDA contents. Strawberry extracts are rich in anthocyanins and present important antioxidant capacity. Ethanol caused severe gastric damage and strawberry consumption protected against its deleterious role. Antioxidant enzyme activities increased significantly after strawberry extract intake and a concomitantly decrease in gastric lipid peroxidation was found. A significant correlation between total anthocyanin content and percent of inhibition of ulcer index was also found. Conclusions Strawberry extracts prevented exogenous ethanol-induced damage to rats' gastric mucosa. These effects seem to be associated with the antioxidant activity and phenolic content in the extract as well as with the capacity of promoting the action of antioxidant enzymes. A diet rich in strawberries might exert a beneficial effect in the prevention of gastric diseases related to generation of reactive oxygen species. PMID:22016781

  18. Preventive Effect of the Korean Traditional Health Drink (Taemyeongcheong) on Acetaminophen-Induced Hepatic Damage in ICR Mice.

    PubMed

    Yi, Ruo-Kun; Song, Jia-Le; Lim, Yaung-Iee; Kim, Yong-Kyu; Park, Kun-Young

    2015-03-01

    This study was to investigate the preventive effect of taemyeongcheong (TMC, a Korean traditional health drink) on acetaminophen (APAP, 800 mg/kg BW)-induced hepatic damage in ICR mice. TMC is prepared from Saururus chinensis, Taraxacum officinale, Zingiber officinale, Cirsium setidens, Salicornia herbacea, and Glycyrrhizae. A high dose of TMC (500 mg/kg BW) was found to decrease APAP-induced increases in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase. TMC pretreatment also increased the hepatic levels of hepatic catalase, superoxide dismutase, glutathione peroxidase, and glutathione, and reduced serum levels of the inflammatory cytokines tumor necrosis factor (TNF)-? and interleukin (IL)-6 in mice administered APAP (P<0.05). TMC (500 mg/kg BW) reduced hepatic mRNA levels of TNF-?, IL-1?, IL-6, COX-2, and iNOS by 87%, 84%, 89%, 85%, and 88%, respectively, in mice treated with APAP (P<0.05). Furthermore, histological observations suggested TMC pretreatment dose-dependently prevented APAP-induced hepatocyte damage. These results suggest that TMC could be used as a functional health drink to prevent hepatic damage. PMID:25866750

  19. Gastroprotective effect of cyanidin 3-glucoside on ethanol-induced gastric lesions in rats

    Microsoft Academic Search

    Chun-Ying Li; Hong-De Xu; Bing-Tian Zhao; Hyo-Ihl Chang; Hae-Ik Rhee

    2008-01-01

    This study investigated the in vivo protective effect of cyanidin 3-glucoside (C3G) against ethanol-induced gastric lesions in rats. The experimental rats were treated with 80% ethanol after pretreatment with various doses of C3G (4 and 8mg\\/kg of body weight), and the control rats received only 80% ethanol. Oral pretreatment with C3G significantly inhibited the formation of ethanol-induced gastric lesions and

  20. Peptide-Mediated Protection from Ethanol-Induced Neural Tube Defects

    Microsoft Academic Search

    Shao-Yu Chen; Michael E. Charness; Michael F. Wilkemeyer; Kathleen K. Sulik

    2005-01-01

    Ethanol inhibition of L1-mediated cell adhesion may contribute to the spectrum of neurological, behavioral and morphological abnormalities associated with prenatal ethanol exposure. We showed previously that the neuroprotective peptides NAPVSIPQ (NAP) and SALLRSIPA (SAL) antagonize ethanol inhibition of L1 adhesion and prevent ethanol-induced growth retardation in mouse whole embryo culture. Here we ask whether NAP and SAL also prevent ethanol-induced

  1. Orthosiphon stamineus leaf extract protects against ethanol-induced gastropathy in rats.

    PubMed

    Yam, Mun Fei; Ang, Lee Fung; Salman, Ibrahim Muhammad; Ameer, Omar Ziad; Lim, Vuanghao; Ong, Lai Man; Ahmad, Mariam; Asmawil, Mohd Zaini; Basir, Rusliza

    2009-10-01

    Orthosiphon stamineus Benth., which is used as a gastroprotective herbal remedy in Malaysia, was assessed for its anti-ulcerogenic activity against ethanol-induced ulcers in rats. Fifty percent methanol was used to extract the oven-dried O. stamineus leaves. The extract was then lyophilized with a rotary evaporator and freeze-dried. Oral administration of O. stamineus methanolic extract (OSME) (125, 250, 500, and 1,000 mg/kg) was found to significantly decrease the ulcer index (P < .01, P < .001, P < .001, and P < .001, respectively). Histological study of a section of the rat stomach also showed a marked improvement in the gastric mucosal damage in groups receiving OSME. In order to further investigate the gastroprotective mechanism of OSME, mucus secretion and lipid peroxidation level were estimated in vitro and ex vivo. OSME exhibited dose-dependent stimulation of mucus secretion (r = 0.718, P < .001) and inhibition of lipid peroxidation in rat gastric mucosal homogenates (both in vitro [r = 0.819, P < .05] and ex vivo [r = 0.981, P < .05]). It was concluded that the gastroprotective mechanism of OSME was partly due to its ability to inhibit lipid peroxidation and stimulate gastric mucus secretion. PMID:19857074

  2. Potassium permanganate toxicity: A rare case with difficult airway management and hepatic damage

    PubMed Central

    Agrawal, Vijay Kumar; Bansal, Abhishek; Kumar, Ranjeet; Kumawat, Bhanwar Lal; Mahajan, Parul

    2014-01-01

    Potassium permanganate (KMnO4) is rarely used for suicidal attempt. Its ingestion can lead to local as well as systemic toxicities due to coagulation necrosis and damage, caused by free radicals of permanganate. We recently managed a case of suicidal ingestion of KMnO4 in a lethal dose. She had significant narrowing of upper airway leading to difficult intubation as well as hepatic dysfunction and coagulopathy as systemic manifestation. We suggest to keep ourselves ready to handle difficult airway with the aid of fiber optic bronchoscope or surgical airway management in such patients. Upper gastrointestinal (GI) endoscopy should be done at the earliest to determine the extent of upper GI injury and further nutrition planning. PMID:25538417

  3. Red Mold Rice against Hepatic Inflammatory Damage in Zn-deficient Rats

    PubMed Central

    Lee, Bao-Hong; Hsu, Wei-Hsuan; Pan, Tzu-Ming

    2012-01-01

    The protective effect of red mold rice (RMR) against liver injury in rats fed with a Zn-deficient diet for 12 weeks was investigated in this study. Rats were orally administered RMR (151 mg/kg body weight or 755 mg/kg body weight; 1 × dose or 5 × dose, respectively) with or without Zn once a day for 4 consecutive weeks. The severity of liver damage was evaluated by measuring the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in Zn-deficient rats. RMR significantly inhibited the elevation of serum ALT levels by Zn-deficient induction. Hepatic antioxidase activity was also significantly increased in the RMR + Zn group (RZ), thereby suppressing the productions of reactive oxygen species (ROS) and proinflammatory cytokines in the liver of Zn-deficient rats. These findings suggested that RMR exerted hepatoprotective effects against Zn deficiency-induced liver inflammation. PMID:24716115

  4. Hepatoprotective Evaluation of Ganoderma lucidum Pharmacopuncture: In vivo Studies of Ethanol-induced Acute Liver Injury

    PubMed Central

    Jang, Sun-Hee; Cho, Sung-woo; Yoon, Hyun-Min; Jang, Kyung-Jeon; Song, Chun-Ho; Kim, Cheol-Hong

    2014-01-01

    Objectives: Alcohol abuse is a public issue and one of the major causes of liver disease worldwide. This study was aimed at investigating the protective effect of Ganoderma lucidum pharmacopuncture (GLP) against hepatotoxicity induced by acute ethanol (EtOH) intoxication in rats. Methods: Sprague-Dawley (SD) rats were divided into 4 groups of 8 animals each: normal, control, normal saline pharmacopuncture (NP) and GLP groups. The control, NP and GLP groups received ethanol orally. The NP and the GLP groups were treated daily with injections of normal saline and Ganoderma lucidum extract, respectively. The control group received no treatment. The rats in all groups, except the normal group, were intoxicated for 6 hours by oral administration of EtOH (6 g/kg BW). The same volume of distilled water was administered to the rats in the normal group. Two local acupoints were used: Qimen (LR14) and Taechung (LR3). A histopathological analysis was performed, and the liver function and the activities of antioxidant enzymes were assessed. Results: GLP treatment reduced the histological changes due to acute liver injury induced by EtOH and significantly reduced the increase in the alanine aminotransferase (ALT) enzyme; however, it had an insignificant effect in reducing the increase in aspartate aminotransferase (AST) enzyme. It also significantly ameliorated the superoxide dismutase (SOD) and the catalase (CAT) activities. Conclusion: The present study suggests that GLP treatment is effective in protecting against ethanol-induced acute hepatic injury in SD rats by modulating the activities of ethanol-metabolizing enzymes and by attenuating oxidative stress. PMID:25780705

  5. Hawk tea (Litsea coreana Levl. var. lanuginose) attenuates CCl(4)-induced hepatic damage in Sprague-Dawley rats.

    PubMed

    Zhao, Xin

    2013-02-01

    Hawk tea (Litsea coreana Levl. var. lanuginose) is a traditional Chinese drink similar to green tea. In the present study, the preventive effects of Hawk tea on hepatic damage induced by carbon tetrachloride (CCl(4)) were studied in Sprague-Dawley rats. Silymarin was used as a positive control. Hawk tea was successfully shown to prevent hepatic damage in the rats. Serum levels of AST, ALT and LDH were significantly decreased when the rats were treated with varying concentrations of Hawk tea compared with silymarin (P<0.05). The lowest enzyme activities were exhibited in the 400 mg/kg Hawk tea group. This group showed reduced levels of the serum proinflammatory cytokines IL-6, IFN-? and TNF-?. In particular, the IFN-? level decreased markedly compared with the other concentration groups. The histopathology sections of liver tissue in the 400 mg/kg Hawk tea group recovered well from the CCl(4) damage, but the sections of the other concentration groups showed necrosis to a more serious degree. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analyses of the inflammation-related genes iNOS, COX-2, TNF-? and IL-1? in the rat livers were tested. The 400 mg/kg Hawk tea group showed significantly decreased mRNA and protein expression levels of iNOS, COX-2, TNF-? and IL-1? compared with the control group. Accordingly, 400 mg/kg Hawk tea potentially contributes to the prevention of CCl(4)-induced hepatic damage in vivo. A 200 or 100 mg/kg dose of Hawk tea also demonstrated preventive effects against hepatic damage. PMID:23403509

  6. Environmental enrichment blocks reinstatement of ethanol-induced conditioned place preference in mice.

    PubMed

    Li, Xinjuan; Meng, Li; Huang, Keyu; Wang, Hua; Li, Dongliang

    2015-07-10

    This study aimed to explore the effect of environmental enrichment (EE) on the reinstatement of ethanol-induced conditioned place preference (CPP) in C57Bl/6J mice. To investigate the effect of training dose on the extinction and relapse of ethanol-induced CPP, doses of ethanol were applied and we found 0.8g/kg and 1.6g/kg training doses lead to significant CPP. In the reinstatement procedure, previously extinguished 1.6g/kg ethanol CPP could be markedly reinstated by a priming injection of 0.8g/kg. In contrast, priming with 0.4g/kg of ethanol failed to reinstate the CPP induced by 0.8g/kg. To investigate whether concomitant EE exposure could prevent the reinstatement of ethanol-induced CPP, one half of the mice were housed in standard environment (SE) and the other half in EE during the extinction and reinstatement session in the second experiment. Our study showed that reinstatement of ethanol-induced CPP was blocked by EE and the extinction rate was the same between SE and EE mice. These findings suggest that EE can block reinstatement of ethanol-induced CPP in mice, and aiding in the identification of new therapeutic strategies for alcohol addiction. PMID:26003446

  7. Neuroprotective effect of osmotin against ethanol-induced apoptotic neurodegeneration in the developing rat brain

    PubMed Central

    Naseer, M I; Ullah, I; Narasimhan, M L; Lee, H Y; Bressan, R A; Yoon, G H; Yun, D J; Kim, M O

    2014-01-01

    Fetal alcohol syndrome is a neurological and developmental disorder caused by exposure of developing brain to ethanol. Administration of osmotin to rat pups reduced ethanol-induced apoptosis in cortical and hippocampal neurons. Osmotin, a plant protein, mitigated the ethanol-induced increases in cytochrome c, cleaved caspase-3, and PARP-1. Osmotin and ethanol reduced ethanol neurotoxicity both in vivo and in vitro by reducing the protein levels of cleaved caspase-3, intracellular [Ca2+]cyt, and mitochondrial transmembrane potential collapse, and also upregulated antiapoptotic Bcl-2 protein. Osmotin is a homolog of adiponectin, and it controls energy metabolism via phosphorylation. Adiponectin can protect hippocampal neurons against ethanol-induced apoptosis. Abrogation of signaling via receptors AdipoR1 or AdipoR2, by transfection with siRNAs, reduced the ability of osmotin and adiponectin to protect neurons against ethanol-induced neurodegeneration. Metformin, an activator of AMPK (adenosine monophosphate-activated protein kinase), increased whereas Compound C, an inhibitor of AMPK pathway, reduced the ability of osmotin and adiponectin to protect against ethanol-induced apoptosis. Osmotin exerted its neuroprotection via Bcl-2 family proteins and activation of AMPK signaling pathway. Modulation of AMPK pathways by osmotin, adiponectin, and metformin hold promise as a preventive therapy for fetal alcohol syndrome. PMID:24675468

  8. Investigation of Antioxidant and Hepatoprotective Activity of Standardized Curcuma xanthorrhiza Rhizome in Carbon Tetrachloride-Induced Hepatic Damaged Rats

    PubMed Central

    Devaraj, Sutha; Ismail, Sabariah; Ramanathan, Surash

    2014-01-01

    Curcuma xanthorrhiza (CX) has been used for centuries in traditional system of medicine to treat several diseases such as hepatitis, liver complaints, and diabetes. It has been consumed as food supplement and “jamu” as a remedy for hepatitis. Hence, CX was further explored for its potential as a functional food for liver related diseases. As such, initiative was taken to evaluate the antioxidant and hepatoprotective potential of CX rhizome. Antioxidant activity of the standardized CX fractions was determined using in vitro assays. Hepatoprotective assay was conducted against carbon tetrachloride- (CCl4-) induced hepatic damage in rats at doses of 125, 250, and 500?mg/kg of hexane fraction. Highest antioxidant activity was found in hexane fraction. In the case of hepatoprotective activity, CX hexane fraction showed significant improvement in terms of a biochemical liver function, antioxidative liver enzymes, and lipid peroxidation activity. Good recovery was observed in the treated hepatic tissues histologically. Hence, the results concluded that CX hexane fraction possessed prominent hepatoprotective activities which might be due to its in vitro antioxidant activity. These findings also support the use of CX as a functional food for hepatitis remedy in traditional medicinal system. PMID:25133223

  9. Hepatitis C, Innate Immunity and Alcohol: Friends or Foes?

    PubMed Central

    Osna, Natalia A.; Ganesan, Murali; Kharbanda, Kusum K.

    2015-01-01

    Hepatitis C and alcohol are the most widespread causes of liver disease worldwide. Approximately 80% of patients with a history of hepatitis C and alcohol abuse develop chronic liver injury. Alcohol consumption in hepatitis C virus (HCV)-infected patients exacerbates liver disease leading to rapid progression of fibrosis, cirrhosis and even hepatocellular carcinoma. Hepatocytes are the main sites of HCV-infection and ethanol metabolism, both of which generate oxidative stress. Oxidative stress levels affect HCV replication and innate immunity, resulting in a greater susceptibility for HCV-infection and virus spread in the alcoholic patients. In this review paper, we analyze the effects of ethanol metabolism and other factors on HCV replication. In addition, we illustrate the mechanisms of how HCV hijacks innate immunity and how ethanol exposure regulates this process. We also clarify the effects of HCV and ethanol metabolism on interferon signaling—a crucial point for activation of anti-viral genes to protect cells from virus—and the role that HCV- and ethanol-induced impairments play in adaptive immunity which is necessary for recognition of virally-infected hepatocytes. In conclusion, ethanol exposure potentiates the suppressive effects of HCV on innate immunity, which activates viral spread in the liver and finally, leads to impairments in adaptive immunity. The dysregulation of immune response results in impaired elimination of HCV-infected cells, viral persistence, progressive liver damage and establishment of chronic infection that worsens the outcomes of chronic hepatitis C in alcoholic patients. PMID:25664450

  10. Early role of the ? opioid receptor in ethanol-induced reinforcement.

    PubMed

    Pautassi, Ricardo Marcos; Nizhnikov, Michael E; Acevedo, Ma Belén; Spear, Norman E

    2012-03-20

    Effects of early ethanol exposure on later ethanol intake emphasize the importance of understanding the neurobiology of ethanol-induced reinforcement early in life. Infant rats exhibit ethanol-induced appetitive conditioning and ethanol-induced locomotor activation, which have been linked in theory and may have mechanisms in common. The appetitive effects of ethanol are significantly modulated by ? and ? opioid receptors, whereas ? but not ? receptors are involved in the motor stimulant effects of ethanol during early development. The involvement of the ? opioid receptor (KOR) system in the motivational effects of ethanol has been much less explored. The present study assessed, in preweanling (infant) rats, the modulatory role of the KOR system in several paradigms sensitive to ethanol-induced reinforcement. Kappa opioid activation and blockade were examined in second-order conditioned place preference with varied timing before conditioning and with varied ethanol doses. The role of KOR on ethanol-induced locomotion and ethanol-induced taste conditioning was also explored. The experiments were based on the assumption that ethanol concurrently induces appetitive and aversive effects and that the latter may be mediated by activation of kappa receptors. The main result was that blockade of kappa function facilitated the expression of appetitive ethanol reinforcement in terms of tactile and taste conditioning. The effects of kappa activation on ethanol conditioning seemed to be independent from ethanol's stimulant effects. Kappa opioid activation potentiated the motor depressing effects of ethanol but enhanced motor activity in control subjects. Overall, the results support the hypothesis that a reduced function of the KOR system in nondependent subjects should attenuate the aversive consequences of ethanol. PMID:22261437

  11. Gastroprotective effects of Corchorus olitorius leaf extract against ethanol-induced gastric mucosal hemorrhagic lesions in rats

    PubMed Central

    Al Batran, Rami; Al-Bayaty, Fouad; Ameen Abdulla, Mahmood; Jamil Al-Obaidi, Mazen M; Hajrezaei, Maryam; Hassandarvish, Pouya; Fouad, Mustafa; Golbabapour, Shahram; Talaee, Samaneh

    2013-01-01

    Background and AimCorchorus olitorius is a medicinal plant traditionally utilized as an antifertility, anti-convulsive, and purgative agent. This study aimed to evaluate the gastroprotective effect of an ethanolic extract of C.?olitorius against ethanol-induced gastric ulcers in adult Sprague Dawley rats. MethodsThe rats were divided into seven groups according to their pretreatment: an untreated control group, an ulcer control group, a reference control group (20?mg/kg omeprazole), and four experimental groups (50, 100, 200, or 400?mg/kg of extract). Carboxymethyl cellulose was the vehicle for the agents. Prior to the induction of gastric ulcers with absolute ethanol, the rats in each group were pretreated orally. An hour later, the rats were sacrificed, and gastric tissues were collected to evaluate the ulcers and to measure enzymatic activity. The tissues were subjected to histological and immunohistochemical evaluations. ResultsCompared with the extensive mucosal damage in the ulcer control group, gross evaluation revealed a marked protection of the gastric mucosa in the experimental groups, with significantly preserved gastric wall mucus. In these groups, superoxide dismutase and malondialdehyde levels were significantly increased (P?ethanol-induced gastric mucosal hemorrhagic lesions in rats. PMID:23611708

  12. Hepatoprotective Effect of Houttuynia cordata Thunb Extract against Carbon Tetrachloride-induced Hepatic Damage in Mice

    PubMed Central

    Kang, H.; Koppula, S.

    2014-01-01

    Houttuynia cordata Thunb (Saururaceae) is a traditional medicinal herb used to treat several disease symptoms. The present study was focused on the hepatoprotective effects of H. cordata ethyl acetate extract in experimental mice. Further the antioxidant potential of the extract was also evaluated to substantiate its hepatoprotective properties. Carbon tetrachloride-induced hepatic damage in mice was used to measure the serum biochemical parameters. Morphological changes in hepatocyte architecture were studied by haematoxylin and eosin staining. In vitro alkyl and hydroxyl free radical scavenging assays were performed to evaluate the antioxidant effect. Administration of H. cordata extract significantly reduced the elevated serum levels and regulated the altered levels of serum cholesterol in carbon tetrachloride-treated mice (P<0.05). The morphological changes in hepatocyte architecture were also reversed by H. cordata treatment. Further, the extract showed significant antioxidant actions by scavenging the alkyl and hydroxyl free radicals. The concentration of the extract necessary for 50% scavenging of alkyl and hydroxyl radicals was 15.5 and 410 ?g/ml, respectively. H. cordata extract exhibited significant hepatoprotective property in carbon tetrachloride-induced hepatotoxicity in mice. The strong antioxidant activities possessed by the extract might be responsible for such actions. PMID:25284923

  13. EARLY MATERNAL SEPARATION AFFECTS ETHANOL-INDUCED CONDITIONING IN A nor-BNI INSENSITIVE MANNER, BUT DOES NOT ALTER ETHANOL-INDUCED LOCOMOTOR ACTIVITY

    PubMed Central

    Pautassi, Ricardo Marcos; Nizhnikov, Michael E.; Fabio, Ma. Carolina; Spear, Norman E.

    2011-01-01

    Early environmental stress significantly affects the development of offspring. This stress has been modeled in rats through the maternal separation (MS) paradigm, which alters the functioning of the HPA axis and can enhance ethanol intake at adulthood. Infant rats are sensitive to ethanol’s reinforcing effects, which modulate ethanol seeking and intake. Little is known about the impact of MS on sensitivity to ethanol’s appetitive and aversive effects during infancy. The present study assessed ethanol-induced conditioned place preference established through second-order conditioning (SOC), spontaneous or ethanol-induced locomotor activity and ethanol intake in preweanling rats that experienced normal animal facility rearing (AFR) or daily episodes of maternal separation (MS) during postnatal days 1-13 (PDs 1-13). Low-ethanol dose (0.5 g/kg) induced appetitive conditioned place preference (via SOC) in control rats given conventional rearing but not in rats given maternal separation in early infancy, whereas 2.0 g/kg ethanol induced aversive conditioned place preference in the former but not the latter. The administration of a kappa antagonist at PD1 or immediately before testing did not alter ethanol-induced reinforcement. High (i.e., 2.5 and 2.0 g/kg) but not low (i.e., 0.5 g/kg) ethanol dose induced reliable motor stimulation, which was independent of early maternal separation. Ethanol intake and blood alcohol levels during conditioning were unaffected by rearing conditions. Pups given early maternal separation had lower body weights than controls and showed an altered pattern of exploration when placed in an open field. These results indicate that, when assessed in infant rats, earlier maternal separation alters the balance between the appetitive and aversive motivational effects of ethanol but has no effect on the motor activating effects of the drug. PMID:22108648

  14. Schisandra Chinensis Baillon regulates the gene expression of phase II antioxidant/detoxifying enzymes in hepatic damage induced rats

    PubMed Central

    Jang, Han I; Do, Gyeong-Min; Lee, Hye Min; Ok, Hyang Mok; Shin, Jae-Ho

    2014-01-01

    BACKGROUND/OBJECTIVES This study investigated the antioxidant activities and hepatoprotective effects of Schisandra chinensis Baillon extract (SCE) against tert-butyl hydroperoxide (t-BHP)-induced oxidative hepatic damage in rats. MATERIALS/METHODS Sprague-Dawley (SD) rats were pretreated with SCE (300, 600, and 1,200 mg/kg BW) or saline once daily for 14 consecutive days. On day 14, each animal, except those belonging to the normal control group, were injected with t-BHP (0.8 mmol/kg BW/i.p.), and all of the rats were sacrificed 16 h after t-BHP injection. RESULTS Although no significant differences in AST and ALT levels were observed among the TC and SCE groups, the high-dose SCE group showed a decreasing tendency compared to the TC group. However, erythrocyte SOD activity showed a significant increase in the low-dose SCE group compared with the TC group. On the other hand, no significant differences in hepatic total glutathione (GSH) level, glutathione reductase (GR), and glutathione peroxidase (GSH-Px) activities were observed among the TC and SCE groups. Hepatic histopathological evaluation revealed that pretreatment with SCE resulted in reduced t-BHP-induced incidence of lesions, such as neutrophil infiltration, swelling of liver cells, and necrosis. In particular, treatment with a high dose of SCE resulted in induction of phase II antioxidant/detoxifying enzyme expression, such as glutathione S-transferase (GST) and glutamate-cysteine ligase catalytic subunit (GCLC). CONCLUSIONS Based on these results, we conclude that SCE exerts protective effects against t-BHP induced oxidative hepatic damage through the reduction of neutrophil infiltration, swelling of liver cells, and necrosis. In addition, SCE regulates the gene expression of phase II antioxidant/detoxifying enzymes independent of hepatic antioxidant enzyme activity. PMID:24944771

  15. Hepatitis

    MedlinePLUS

    ... with hepatitis show no signs of having the disease, but others may have these symptoms: tiredness without another reason flu-like symptoms — throwing up, feeling hot, etc. yellowing of skin and whites of eyes belly pain (especially on the upper ...

  16. Matcha, a powdered green tea, ameliorates the progression of renal and hepatic damage in type 2 diabetic OLETF rats.

    PubMed

    Yamabe, Noriko; Kang, Ki Sung; Hur, Jong Moon; Yokozawa, Takako

    2009-08-01

    Matcha, a powdered green tea produced by grinding with a stone mill, has been popularly used in the traditional tea ceremony and foods in Japan. Matcha is well known to be richer in some nutritional elements and epigallocatechin 3-O-gallate than other green teas. In our previous study, epigallocatechin 3-O-gallate exhibited protective effects against renal damage in a rat model of diabetic nephropathy. In the present study, we investigated the preventive effects of Matcha (50, 100, or 200 mg/kg/day) on the progression of hepatic and renal damage in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. OLETF rats were orally administered Matcha for 16 weeks, and we assessed biochemical parameters in the serum, liver, and kidney and expression levels of major products of advanced glycation end products (AGEs), N(6)-(carboxylmethyl)lysine (CML) and N(6)-(carboxylethyl)lysine (CEL), receptor for AGE (RAGE), and sterol regulatory element binding proteins (SREBPs)-1 and -2. Serum total protein levels were significantly increased by Matcha administration, whereas the serum albumin and glycosylated protein levels as well as the renal glucose and triglyceride levels were only slightly or not at all affected. However, Matcha treatment significantly lowered the glucose, triglyceride, and total cholesterol levels in the serum and liver, renal AGE levels, and the serum thiobarbituric acid-reactive substances levels. In addition, Matcha supplementation resulted in decreases in the renal CML, CEL, and RAGE expressions as well as an increase in hepatic SREBP-2 expression, but not that of SREBP-1. These results suggest that Matcha protects against hepatic and renal damage through the suppression of renal AGE accumulation, by decreases in hepatic glucose, triglyceride, and total cholesterol levels, and by its antioxidant activities. PMID:19735169

  17. Ethanol-Induced Alterations in Purkinje Neuron Dendrites in Adult and Aging Rats: a Review.

    PubMed

    Dlugos, Cynthia A

    2015-08-01

    Uncomplicated alcoholics suffer from discrete motor dysfunctions that become more pronounced with age. These deficits involve the structure and function of Purkinje neurons (PN), the sole output neurons from the cerebellar cortex. This review focuses on alterations to the PN dendritic arbor in the adult and aging Fischer 344 rat following lengthy alcohol consumption. It describes seminal studies using the Golgi-Cox method which proposed a model for ethanol-induced dendritic regression. Subsequent ultrastructural studies of PN dendrites showed dilation of the extensive smooth endoplasmic reticulum (SER) which preceded and accompanied dendritic regression. The component of the SER that was most affected by ethanol was the sarco/endoplasmic reticulum Ca(2+) ATPase pump (SERCA) responsible for resequestration of calcium into the SER. Ethanol-induced decreases in SERCA pump levels, similar to the finding of SER dilation, preceded and occurred concomitantly with dendritic regression. Discrete ethanol-induced deficits in balance also accompanied these decreases. Ethanol-induced ER stress within the SER of PN dendrites was proposed as an underlying cause of dendritic regression. It was recently shown that increased activation of caspase 12, inherent to the ER, occurred in PN of acute slices in ethanol-fed rats and was most pronounced following 40 weeks of ethanol treatment. These findings shed new light into alcohol-induced disruption in PN dendrites providing a new model for the discrete but critical changes in motor function in aging, adult alcoholics. PMID:25648753

  18. Ethanol-induced injury in rat primary cortical astrocytes involves oxidative stress: effect of idebenone

    Microsoft Academic Search

    Carolina Muscoli; Massimo Fresta; Venera Cardile; Maddalena Palumbo; Marcella Renis; Giovanni Puglisi; Donatella Paolino; Steven Nisticò; Domenicantonio Rotiroti; Vincenzo Mollace

    2002-01-01

    Ethanol-induced neurological disorders have recently been characterised. Indeed, evidence has been collected indicating that chronic ethanol consumption leads to direct or indirect changes in the viability of central nervous system cells. Here we investigated the role of free radical overproduction in primary cortical rat astroglial cells undergoing chronic treatment with ethanol (100 ?M). In particular, exposure of astroglial cell cultures

  19. Lithium blocks ethanol-induced modulation of protein kinases in the developing brain

    SciTech Connect

    Chakraborty, Goutam [Laboratory of Neurobehavior Genetics, The Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962 (United States); Department of Chemistry and Biochemistry, Montclair State University, Upper Montclair, NJ 07043 (United States); Saito, Mitsuo [Division of Analytical Psychopharmacology, The Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962 (United States); Department of Psychiatry, New York University Medical Center, New York, NY 10016 (United States); Mao, Rui-Fen; Wang, Ray [Laboratory of Neurobehavior Genetics, The Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962 (United States); Vadasz, Csaba [Laboratory of Neurobehavior Genetics, The Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962 (United States); Department of Psychiatry, New York University Medical Center, New York, NY 10016 (United States); Saito, Mariko [Laboratory of Neurobehavior Genetics, The Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962 (United States); Department of Psychiatry, New York University Medical Center, New York, NY 10016 (United States)], E-mail: marsaito@nki.rfmh.org

    2008-03-14

    Lithium has been shown to be neuroprotective against various insults including ethanol exposure. We previously reported that ethanol-induced apoptotic neurodegeneration in the postnatal day 7 (P7) mice is associated with decreases in phosphorylation levels of Akt, glycogen synthase kinase-3{beta} (GSK-3{beta}), and AMP-activated protein kinase (AMPK), and alteration in lipid profiles in the brain. Here, P7 mice were injected with ethanol and lithium, and the effects of lithium on ethanol-induced alterations in phosphorylation levels of protein kinases and lipid profiles in the brain were examined. Immunoblot and immunohistochemical analyses showed that lithium significantly blocked ethanol-induced caspase-3 activation and reduction in phosphorylation levels of Akt, GSK-3{beta}, and AMPK. Further, lithium inhibited accumulation of cholesterol ester (ChE) and N-acylphosphatidylethanolamine (NAPE) triggered by ethanol in the brain. These results suggest that Akt, GSK-3{beta}, and AMPK are involved in ethanol-induced neurodegeneration and the neuroprotective effects of lithium by modulating both apoptotic and survival pathways.

  20. ALTERED RA SIGNALING IN THE GENESIS OF ETHANOL-INDUCED LIMB DEFECTS

    EPA Science Inventory

    Altered RA Signaling in the Genesis of Ethanol-Induced Limb Defects Johnson CS(1), Sulik KK(1,2) Hunter, ES III(3) (1) Dept of Cell and Developmental Biology, UNC-Chapel Hill (2) Bowles Center for Alcohol Studies, UNC-CH (3) NHEERL, ORD, US EPA, RTP, NC Administr...

  1. MECHANISMS OF ETHANOL-INDUCED BONE LOSS DIFFER WITH PHYSIOLOGICAL STATE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Clinical surveys indicate that heavy drinking is a risk factor for the development of osteoporosis. However, the molecular mechanisms underlying ethanol-induced bone loss remain the subject of dispute with some studies showing ethanol effects on bone formation and others on bone breakdown. In thes...

  2. Resveratrol, a red wine polyphenol, attenuates ethanol-induced oxidative stress in rat liver.

    PubMed

    Kasdallah-Grissa, Abir; Mornagui, Bessem; Aouani, Ezzedine; Hammami, Mohamed; El May, Michelle; Gharbi, Najoua; Kamoun, Abdelaziz; El-Fazaâ, Saloua

    2007-02-20

    The involvement of oxidative stress in the pathogenesis of alcoholic diseases in the liver has been repeatedly confirmed. Resveratrol, a natural phytoalexin present in grape skin and red wine possesses a variety of biological activities including antioxidant. This study was conducted to evaluate whether resveratrol has a preventive effect on the main indicators of hepatic oxidative status as an expression of the cellular damage caused by free radicals, and on antioxidant defence mechanism during chronic ethanol treatment. Wistar rats were treated daily with 35% ethanol solution (3 g/kg/day i.p.) during 6 weeks and fed basal diet or basal diet containing 5 g/kg resveratrol. Control rats were treated with i.p. saline and fed basal diet. Experimentally, chronic ethanol administration leads to hepatotoxicity as monitored by the increase in the level of hepatic marker enzymes and the appearance of fatty change, necrosis, fibrosis and inflammation in liver sections. Ethanol also enhanced the formation of MDA in the liver indicating an increase in lipid peroxidation, a major end-point of oxidative damage, and caused drastic alterations in antioxidant defence systems. Particularly the activities of hepatic superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were found reduced by ethanol treatment while glutathione reductase (GR) activity was unchanged. Dietary supplementation with resveratrol during ethanol treatment inhibited hepatic lipid peroxidation and ameliorated SOD, GPx and CAT activities in the liver. Conclusively, we can suggest that resveratrol could have a beneficial effect in inhibiting the oxidative damage induced by chronic ethanol administration, which was proved by the experiments that we conducted on rats. PMID:17258234

  3. Reversing gastric mucosal alterations during ethanol-induced chronic gastritis in rats by oral administration of Opuntia ficus-indica mucilage

    PubMed Central

    Vázquez-Ramírez, Ricardo; Olguín-Martínez, Marisela; Kubli-Garfias, Carlos; Hernández-Muñoz, Rolando

    2006-01-01

    AIM: To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica (Cactaceae) on the healing of ethanol-induced gastritis in rats. METHODS: Chronic gastric mucosa injury was treated with mucilage (5 mg/kg per day) after it was induced by ethanol. Lipid composition, activity of 5’-nucleotidase (a membrane-associated ectoenzyme) and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined. Histological studies of gastric samples from the experimental groups were included. RESULTS: Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes. Phosphatidylcholine (PC) decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect. The activity of 5’-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes. CONCLUSION: The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids, mainly PC and phosphatidylethanolamine (PE), may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage. PMID:16865772

  4. Aripiprazole an atypical antipsychotic protects against ethanol induced gastric ulcers in rats.

    PubMed

    Asmari, Abdulrahman Al; Arshaduddin, Mohammed; Elfaki, Ibrahim; Kadasah, Saeed; Robayan, Abdulrahman Al; Asmary, Saeed Al

    2014-01-01

    The present investigation was undertaken, to study the gastro-protective potential of aripiprazole (ARI) an atypical antipsychotic drug in ethanol induced gastric ulcers in rats. ARI (10, 30, 100 mg/kg) was tested for gastric secretion and antiulcer activity in different groups of male Sprague Dawley rats. Gastric secretion and acidity studies were performed in pylorus ligated rats while indices of gastric ulcers were measured in ethanol (1 ml-100%) induced gastric ulcers. Histological changes and the levels of gastric wall mucus, malondialdehyde (MDA), non-protein sulfhydryls (NP-SH), myeloperoxidase (MPO), and serotonin were used to assess ethanol induced gastric mucosal injuries. Exposure of rats to ethanol resulted in gastric mucosal injury and a high index of ulcer. Pretreatment with ARI significantly (P < 0.001), reduced the gastric lesions induced by ethanol and also resulted in a significant decrease in the gastric secretion, and total acidity in pylorus ligated rats. ARI also significantly attenuated the ethanol induced reduction in the levels of gastric wall mucus, and NP-SH (P < 0.001). The histological changes and the increased MDA and MPO activity were also significantly (P < 0.001) inhibited by ARI. Ethanol induced depletion in the levels of serotonin in the gastric tissue were also significantly restored by pretreatment with ARI (p < 0.001). ARI showed significant antiulcer and gastroprotective activity against ethanol induced gastric ulcers. The gastroprotective effects of ARI may be due to its anti-secretory, antioxidant and anti-inflammatory action and also due to the restoration of the depleted gastric serotonin levels. PMID:25232384

  5. Suppression of intralysosomal proteolysis aggravates structural damage and functional impairment of liver lysosomes in rats with toxic hepatitis

    SciTech Connect

    Korolenko, T.A.; Gavrilova, N.I.; Kurysheva, N.G.; Malygin, A.E.; Pupyshev, A.B.

    1986-01-01

    This paper estimates the effect of lowering protein catabolism in the lysosomes on structural and functional properties of the latter during liver damage. For comparison, polyvinylpyrrolidone (PVP), which is inert relative to intralysosomal proteolysis, and which also accumulates largely in lysosomes of the kupffer cells of the liver, was used. The uptake of labeled bovine serum albuman (C 14-BSA) by the liver is shown and the rate of intralysosomal proteolysis is given 24 hours after administration of suramin an CCl/sub 4/ to rats. It is suggested that it is risky to use drugs which inhibit intralysosomal proteolysis in the treatment of patients with acute hepatitis.

  6. Brain catalase activity is highly correlated with ethanol-induced locomotor activity in mice.

    PubMed

    Correa, M; Sanchis-Segura, C; Aragon, C M

    2001-07-01

    It has been demonstrated that acute administration of lead to mice enhances brain catalase activity and ethanol-induced locomotion. These effects of lead seem to be related, since they show similar time courses and occur at similar doses. In the present study, in an attempt to further evaluate the relation between brain catalase activity and lead-induced changes in ethanol-stimulated locomotion, the interaction between lead acetate and 3-amino-1H,2,4-triazole (AT), a well-known catalase inhibitor, was assessed. In this study, lead acetate or saline was acutely injected intraperitoneally to Swiss mice at doses of 50 or 100 mg/kg 7 days before testing. On the test day, animals received an intraperitoneal injection of AT (0, 10, or 500 mg/kg). Five hours following AT treatment, ethanol (0.0 or 2.5 g/kg, ip) was injected and the animals were placed in open-field chambers, in which locomotion was measured for 10 min. Neither lead exposure nor AT administration, either alone or in combination, had any effect on spontaneous locomotor activity. AT treatment reduced ethanol-induced locomotion as well as brain catalase activity. On the other hand, ambulation and brain catalase activity were significantly increased by both doses of lead. Furthermore, AT significantly reduced the potentiation produced by lead acetate on brain catalase and on ethanol-induced locomotor activity in a dose-dependent manner. A significant correlation was found between locomotion and catalase activity across all test conditions. The results show that brain catalase activity is involved in the effects of lead acetate on ethanol-induced locomotion in mice. Thus, this study confirms the notion that brain catalase provides the molecular basis for understanding some of the mechanisms of the action of ethanol in the central nervous system. PMID:11495670

  7. Study on treating ethanol-induced gastric lesions with omeprazole, Nigella sativa oil, or both

    Microsoft Academic Search

    Thanaa A. El-Masry; Abdulla M. Elahwel; Ashraf M. Emara

    2010-01-01

    Ethanol is among the many factors increasing the risk of gastric ulcer formation such as stress, use of steroids, and non-steroidal anti-inflammatory drugs. This study was conducted to determine the role of reactive oxygen species in the pathogenesis of ethanol-induced gastric lesions and its treatment with omeprazole, corn oil, Nigella sativa oil, and combinations thereof. Rats were divided into: Group

  8. Role of chemokines and their receptors in viral persistence and liver damage during chronic hepatitis C virus infection.

    PubMed

    Larrubia, Juan R; Benito-Martínez, Selma; Calvino, Miryam; Sanz-de-Villalobos, Eduardo; Parra-Cid, Trinidad

    2008-12-21

    Chemokines produced in the liver during hepatitis C virus (HCV) infection induce migration of activated T cells from the periphery to infected parenchyma. The milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper cell/Tc1 T cell (Th1/Tc1) response. These chemokines consist of CCL3 (macrophage inflammatory protein-1 alpha; MIP-1 alpha), CCL4 (MIP-1 beta), CCL5 (regulated on activation normal T cell expressed and secreted; RANTES), CXCL10 (interferon-gamma-inducible protein-10; IP-10), CXCL11 (interferon-inducible T-cell alpha chemoattractant; I-TAC), and CXCL9 (monokine induced by interferon gamma; Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine receptors. Intrahepatic and peripheral blood levels of these chemokines are increased during chronic hepatitis C. The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection. When the adaptive immune response fails in this task, non-specific T cells without the capacity to control the infection are also recruited to the liver, and these are ultimately responsible for the persistent hepatic damage. The modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection, and to maintain liver viability during the chronic phase, by impairing non-specific T cell migration. Some chemokines and their receptors correlate with liver damage, and CXCL10 (IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response outcome. The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver. PMID:19084927

  9. Role of chemokines and their receptors in viral persistence and liver damage during chronic hepatitis C virus infection

    PubMed Central

    Larrubia, Juan R; Benito-Martínez, Selma; Calvino, Miryam; Sanz-de-Villalobos, Eduardo; Parra-Cid, Trinidad

    2008-01-01

    Chemokines produced in the liver during hepatitis C virus (HCV) infection induce migration of activated T cells from the periphery to infected parenchyma. The milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper/T-cytotoxic type-1 cell (Th1/Tc1) response. These chemokines consist of CCL3 (macrophage inflammatory protein-1?; MIP-1?), CCL4 (MIP-1?), CCL5 (regulated on activation normal T cell expressed and secreted; RANTES), CXCL10 (interferon-??inducible protein-10; IP-10), CXCL11 (interferon-inducible T-cell ? chemoattractant; I-TAC), and CXCL9 (monokine induced by interferon ?; Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine receptors. Intrahepatic and peripheral blood levels of these chemokines are increased during chronic hepatitis C. The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection. When the adaptive immune response fails in this task, non-specific T cells without the capacity to control the infection are also recruited to the liver, and these are ultimately responsible for the persistent hepatic damage. The modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection, and to maintain liver viability during the chronic phase, by impairing non-specific T cell migration. Some chemokines and their receptors correlate with liver damage, and CXCL10 (IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response outcome. The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver. PMID:19084927

  10. Deficient PKR in RAX/PKR Association Ameliorates Ethanol-Induced Neurotoxicity in the Developing Cerebellum.

    PubMed

    Li, Hui; Chen, Jian; Qi, Yuanlin; Dai, Lu; Zhang, Mingfang; Frank, Jacqueline A; Handshoe, Jonathan W; Cui, Jiajun; Xu, Wenhua; Chen, Gang

    2015-08-01

    Ethanol-induced neuronal loss is closely related to the pathogenesis of fetal alcohol spectrum disorders. The cerebellum is one of the brain areas that are most sensitive to ethanol. The mechanism underlying ethanol neurotoxicity remains unclear. Our previous in vitro studies have shown that the double-stranded RNA (dsRNA)-activated protein kinase (PKR) regulates neuronal apoptosis upon ethanol exposure and ethanol activates PKR through association with its intracellular activator RAX. However, the role of PKR and its interaction with RAX in vivo have not been investigated. In the current study, by utilizing N-PKR-/- mice, C57BL/6J mice with a deficient RAX-binding domain in PKR, we determined the critical role of RAX/PKR association in PKR-regulated ethanol neurotoxicity in the developing cerebellum. Our data indicate that while N-PKR-/- mice have a similar BAC profile as wild-type mice, ethanol induces less brain/body mass reduction as well as cerebellar neuronal loss. In addition, ethanol promotes interleukin-1? (IL-1?) secretion, and IL-1? is a master cytokine regulating inflammatory response. Importantly, ethanol-promoted IL-1? secretion is inhibited in the developing cerebellum of N-PKR-/- mice. Thus, RAX/PKR interaction and PKR activation regulate ethanol neurotoxicity in the developing cerebellum, which may involve ethanol-induced neuroinflammation. Further, PKR could be a possible target for pharmacological intervention to prevent or treat fetal alcohol spectrum disorder (FASD). PMID:25592072

  11. Ethanol and liver: recent advances in the mechanisms of ethanol-induced hepatosteatosis.

    PubMed

    Zeng, Tao; Xie, Ke-Qin

    2009-12-01

    Ethanol-induced fatty liver is a worldwide health problem without effective therapeutic methods. The underlying mechanisms are extremely complex and not fully understood. The hepatosteatosis caused by ethanol can be attributed to many factors, including the changes of the redox condition, transportation impairment of the synthesized lipid, inhibition of fatty acid oxidation, and the enhancement of the lipogenesis. Recent studies focus on the reduced oxidation of fatty acid and the enhancement of the do novo lipogenesis, and several factors are sequentially revealed. Two important nuclear transcription factors, peroxisome proliferators-activated receptor ? (PPAR?) and sterol regulatory element binding protein-1 (SREBP-1), and the lipid metabolism-associated enzymes regulated by the two molecules, are shown to be involved in ethanol-induced steatosis. The AMP-dependent protein kinase, adiponectin, and tumor necrosis factor ? (TNF-?) may mediate the modulation of ethanol on PPAR? and SREBP-1. In addition, a number of studies demonstrate that plasminogen activator inhibitor-1 (PAI-1) is also involved in ethanol- induced fatty liver, and its effects may be associated with the TNF-? production. Furthermore, the role of CYP2E1 has also been investigated. Some studies showed that CYP2E1 played a critical role in the development of alcoholic fatty liver, which was denied by other reports. As such, the exact role of CYP2E1 needs to be further studied. PMID:19588123

  12. Characterization of an ethanol-inducible promoter system in Catharanthus roseus hairy roots.

    PubMed

    Peebles, Christie A M; Gibson, Susan I; Shanks, Jacqueline V; San, Ka-Yiu

    2007-01-01

    Efforts to engineer Catharanthus roseus hairy roots to produce commercially significant amounts of valuable compounds, such as the terpenoid indole alkaloids vinblastine and vincristine, require the development of tools to study the effects of overexpressing key metabolic and regulatory genes. The use of inducible promoters allows researchers to control the timing and level of expression of genes of interest. In addition, use of inducible promoters allows researchers to use a single transgenic line as both the control and experimental line, minimizing the problems associated with clonal variation. We have previously characterized the use of a glucocorticoid-inducible promoter system to study the effects of gene overexpression within the terpenoid indole alkaloid pathway on metabolite production. Here the feasibility of using an ethanol-inducible promoter within C. roseus hairy roots is reported. This ethanol-inducible promoter is highly sensitive to ethanol concentration with a concentration of 0.005% ethanol causing a 6-fold increase in CAT reporter activity after 24 h of induction. The ethanol-inducible CAT activity increased 24-fold over a 72-h induction period with 0.5% ethanol. PMID:17715939

  13. Scutellariae radix extracts suppress ethanol-induced caspase-11 expression and cell death in N 2a cells

    Microsoft Academic Search

    Kyounglan Kang; Yeo Kyoung Oh; Ryowon Choue; Shin Jung Kang

    2005-01-01

    Scutellariae radix is a Chinese herbal medicine that has been used to treat disease conditions accompanying inflammation and oxidative stress. In the present study, we examined the effect of Scutellariae radix extracts during acute ethanol exposure in N2a neuroblastoma. The Scutellariae radix extracts effectively inhibited ethanol-induced apoptosis and caspase-3\\/-7 activation. Ethanol induced the expression of caspase-11 that has been known

  14. Gastroprotective effect of taurine zinc solid dispersions against absolute ethanol-induced gastric lesions is mediated by enhancement of antioxidant activity and endogenous PGE2 production and attenuation of NO production.

    PubMed

    Yu, Chuan; Mei, Xue-Ting; Zheng, Yan-Ping; Xu, Dong-Hui

    2014-10-01

    Zinc plays a key role in maintaining gastric mucosal integrity, while alcohol dependency can lead to low zinc status. Complexes containing zinc have been reported to have better ability to protect gastric mucosa than the compounds alone. In this study, taurine zinc [Zn(NH3CH2CH2SO3)2] solid dispersions (SDs) were synthesized and investigated in an ethanol-induced ulcer model in rats. Gastric ulcer index; gastric mucosa malondialdehyde (MDA) level, glutathione (GSH) content, superoxide dismutase (SOD) activity and prostaglandin E2 (PGE2) production; and serum nitric oxide (NO) were assessed and histological analysis of the gastric mucosa tissue was performed. Taurine zinc (100, 200 mg/kg) SDs protected rat gastric mucosa from ethanol-induced injury. Moreover, the gastroprotective effect of taurine zinc SDs was accompanied by a decrease in serum NO and significant increase in gastric prostaglandin E2 (PGE2). When indomethacin, a non-selective COX inhibitor was administered before the last dose of taurine zinc, the gastroprotective effect of taurine zinc was weakened. Furthermore, taurine zinc (200 mg/kg) SDs protected against ulceration more significantly than the same dose of taurine alone, suggesting a synergistic effect between taurine and zinc. These results indicate taurine zinc protects the gastric mucosa against ethanol-induced damage by elevating antioxidants, decreasing lipid peroxidation and inhibiting the production of nitric oxide. The gastroprotective effect of taurine zinc was also partially mediated by endogenous PGE2 production. PMID:25041839

  15. CMZ Reversed Chronic Ethanol-Induced Disturbance of PPAR-? Possibly by Suppressing Oxidative Stress and PGC-1? Acetylation, and Activating the MAPK and GSK3? Pathway

    PubMed Central

    Zeng, Tao; Zhang, Cui-Li; Song, Fu-Yong; Zhao, Xiu-Lan; Xie, Ke-Qin

    2014-01-01

    Background Cytochrome P4502E1 (CYP2E1) has been suggested to play critical roles in the pathogenesis of alcoholic fatty liver (AFL), but the underlying mechanisms remains unclear. The current study was designed to evaluate whether CYP2E1 suppression by chlormethiazole (CMZ) could suppress AFL in mice, and to explore the underlying mechanisms. Methods Mice were treated with or without CMZ (50 mg/kg bw, i.p.) and subjected to liquid diet with or without ethanol (5%, w/v) for 4 weeks. Biochemical parameters were measured using commercial kits. The protein and mRNA levels were detected by western blot and qPCR, respectively. Histopathology and immunohistochemical assay were performed with routine methods. Results CYP2E1 inhibition by CMZ completely blocked AFL in mice, shown as the decline of the hepatic and serum triglyceride levels, and the fewer fat droplets in the liver sections. Chronic ethanol exposure led to significant decrease of the mRNA and protein levels of peroxisome proliferator-activated receptor ? (PPAR-?), which was blocked by CMZ co-treatment. CMZ co-treatment suppressed ethanol-induced oxidative stress, overproduction of tumor necrosis ? (TNF-?), and decrease of protein levels of the PPAR-? co-activators including p300 and deacetylated PGC1-?. Furthermore, CMZ co-treatment led to the activation of AMP-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK), and PI3K/Akt/GSK3? pathway. However, chronic ethanol-induced decline of acyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) protein levels was partially restored by CMZ, while the activation of autophagy appeared to be suppressed by CMZ. Conclusion These results suggested that CMZ suppressed chronic ethanol-induced oxidative stress, TNF-? overproduction, decline of p300 protein level and deacetylation of PGC1-?, and activated AMPK, MAPK, and PI3K/Akt/GSK3? pathway, which might contribute to the activation of PPAR-? and account for the protection of CMZ against AFL. PMID:24892905

  16. Delayed onset of severe hepatitis C-related liver damage following liver transplantation: a matter of concern?

    PubMed

    Berenguer, Marina; Aguilera, Victoria; Prieto, Martin; Carrasco, Domingo; Rayón, Miguel; San Juan, Fernando; Landaverde, Carmen; Mir, José; Berenguer, Joaquín

    2003-11-01

    Although histological hepatitis occurs in the majority of hepatitis C virus (HCV)-infected liver transplant recipients, the natural history is highly variable. Whereas progression to cirrhosis occurs in up to 30% after 3 to 7 years, the disease remains stable in another third of patients, in whom protocol liver biopsies might be avoided. However, there is recent concern that with prolonged follow-up, some patients with initial benign recurrence may develop a late-onset aggressive course. Aims of the study are to determine the incidence and factors associated with this event. Based on yearly protocol biopsies (median, five biopsies; range, three to seven biopsies), we evaluated the histological outcome of 57 HCV type 1b-infected transplant recipients with initial benign recurrence, defined as stable histological state (fibrosis stage F0 or F1) during the first 3 years posttransplantation. Severe late-onset liver damage is defined as progression to F3 or F4 in patients with previous benign recurrence. Potential predictors of this event include demographics, donor-related factors, liver enzyme levels at 1 and 3 (or baseline) years posttransplantation, activity grade and fibrosis stage at 1 and 3 years posttransplantation, nonalcoholic steatohepatitis-related variables occurring within the first 3 years posttransplantation (diabetes, hyperlipidemia, obesity), use of some drugs (renin-angiotensin inhibitors, ursodeoxycholic acid), and the advent of any unusual event. The incidence of severe late-onset liver damage was 35% (n = 20). Twelve transplant recipients progressed to F3, whereas 8 transplant recipients progressed to F4. Sudden histological deterioration was observed on postoperative biopsy 5 in 12 patients; biopsy 6 or 7, in 7 patients; and biopsy 4, in 1 patient. Variables associated with this event in univariate analysis were fibrosis stage and activity grade (and its components) at baseline (P <.0001), recipient female gender (P =.04), alanine aminotransferase (ALT) level at 1 year posttransplantation (P =.02), and aspartate aminotransferase (AST) and ALT levels at baseline (P =.008 and P =.005, respectively). By multivariate analysis, only one variable was retained in the model: fibrosis stage at baseline (relative risk, 11; 95% confidence interval, 3 to 41; P =.0007), whereas AST level almost reached statistical significance (P =.07). In conclusion, delayed HCV-related severe liver damage is not infrequent in transplant recipients with initial benign recurrence, occurring in approximately one third of them. The presence of some degree of fibrosis at baseline appears to predict this sudden change in the natural history of recurrent hepatitis C. Based on these findings, we recommend continuing protocol biopsies and evaluating potential antiviral therapy in transplant recipients with evidence of some fibrosis (even if it is only portal). PMID:14586875

  17. Inhibitory effect on proliferation of vascular smooth muscle cells and protective effect on CCl 4-induced hepatic damage of HEAI extract

    Microsoft Academic Search

    Won-Sik Choi; Chang-Jin Kim; Byeoung-Soo Park; Sung-Eun Lee; Gary R. Takeoka; Dong-Goo Kim; Xiang LanPiao; Jeong-Han Kim

    2005-01-01

    The effects of methanol extract from Hericium erinaceus cultivated with Artemisia iwayomogi (HEAI) on proliferation of vascular smooth muscle cells and CCl4-induced hepatic damage were evaluated. HEAI was shown to have a potent inhibitory effect on the proliferation of vascular smooth muscle cells (VSMCs). Interestingly, a methanol extract of Hericium erinaceus showed no inhibitory effect on the proliferation of VSMCs,

  18. Menhaden oil decreases high-fat diet-induced markers of hepatic damage, steatosis, inflammation, and fibrosis in obese Ldlr-/- mice.

    PubMed

    Depner, Christopher M; Torres-Gonzalez, Moises; Tripathy, Sasmita; Milne, Ginger; Jump, Donald B

    2012-08-01

    The frequency of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) has increased in parallel with obesity in the United States. NASH is progressive and characterized by hepatic damage, inflammation, fibrosis, and oxidative stress. Because C20-22 (n-3) PUFA are established regulators of lipid metabolism and inflammation, we tested the hypothesis that C20-22 (n-3) PUFA in menhaden oil (MO) prevent high-fat (HF) diet-induced fatty liver disease in mice. Wild-type (WT) and Ldlr(-/-) C57BL/6J mice were fed the following diets for 12 wk: nonpurified (NP), HF with lard (60% of energy from fat), HF-high-cholesterol with olive oil (HFHC-OO; 54.4% of energy from fat, 0.5% cholesterol), or HFHC-OO supplemented with MO (HFHC-MO). When compared with the NP diet, the HF and HFHC-OO diets induced hepatosteatosis and hepatic damage [elevated plasma alanine aminotransferase (ALT) and aspartate aminotransferases] and elevated hepatic expression of markers of inflammation (monocyte chemoattractant protein-1), fibrosis (procollagen 1?1), and oxidative stress (heme oxygenase-1) (P ? 0.05). Hepatic damage (i.e., ALT) correlated (r = 0.74, P < 0.05) with quantitatively higher (>140%, P < 0.05) hepatic cholesterol in Ldlr(-/-) mice fed the HFHC-OO diet than WT mice fed the HF or HFHC-OO diets. Plasma and hepatic markers of liver damage, steatosis, inflammation, and fibrosis, but not oxidative stress, were lower in WT and Ldlr(-/-) mice fed the HFHC-MO diet compared with the HFHC-OO diet (P < 0.05). In conclusion, MO [C20-22 (n-3) PUFA at 2% of energy] decreases many, but not all, HF diet-induced markers of fatty liver disease in mice. PMID:22739374

  19. Oxidative Damage of Decabromodiphenyl Ether (BDE209) on the Hepatic Cells of Rat in vitro

    Microsoft Academic Search

    Yao Wen-hao; Jiang Ming-di; Hu Qin-qin; Li Ren; Yang Xu

    2010-01-01

    Owing to its good flame-retardant effect, polybrominated diphenyl ethers (PBDEs) were widely added to electronic, electrical appliances, as well as textiles and chemical products. Decabromodiphenyl Ether (BDE-209) is one class of PBDEs which was most demanded in international market. To illustrate the possible function of BDE-209 on rat liver, hepatic cells were expose to BDE-209 with different concentrations (1, 2,

  20. Early termination of immune tolerance state of hepatitis B virus infection explains liver damage

    PubMed Central

    Mamun-Al-Mahtab; Akbar, Sheikh Mohammad Fazle; Uddin, Helal; Khan, Sakirul Islam; Rahman, Salimur

    2014-01-01

    AIM: To assess an early termination of immune tolerance state of chronic hepatitis B virus infection in Bangladesh and its clinical significance. METHODS: From a series of 167 treatment-naive chronic hepatitis B patients aged between 12 to 20 years (mean ± SD; 17.5 ± 2.8 years), percutaneous liver biopsies of 89 patients who were all hepatitis B e antigen negative at presentation were done. Of them, 81 were included in the study. They had persistently normal or raised serum alanine aminotransferase (ALT) values. A precore mutation (PCM) study was accomplished in 8 patients who were randomly selected. RESULTS: Forty-four (53.7%) patients had significant necroinflammation (HAI-NI > 7), while significant fibrosis (HAI-F ? 3) was seen in 15 (18.5%) patients. Serum ALT (cut off 42 U/L) was raised in 29 (35.8%) patients, while low HBV DNA load (< 105 copies/mL) was observed in 57 (70.4%) patients. PCM was negative in all 8 patients. CONCLUSION: This study indicates that the current concept of age-related immune tolerance state of HBV infection deserves further analyses in different population groups. PMID:25232455

  1. Acetaminophen increases the risk of arsenic-mediated development of hepatic damage in rats by enhancing redox-signaling mechanism.

    PubMed

    Majhi, Chhaya Rani; Khan, Saleem; Leo, Marie Dennis Marcus; Prawez, Shahid; Kumar, Amit; Sankar, Palanisamy; Telang, Avinash Gopal; Sarkar, Souvendra Nath

    2014-02-01

    We evaluated whether the commonly used analgesic-antipyretic drug acetaminophen can modify the arsenic-induced hepatic oxidative stress and also whether withdrawal of acetaminophen administration during the course of long-term arsenic exposure can increase susceptibility of liver to arsenic toxicity. Acetaminophen was co-administered orally to rats for 3 days following 28 days of arsenic pre-exposure (Phase-I) and thereafter, acetaminophen was withdrawn, but arsenic exposure was continued for another 28 days (Phase-II). Arsenic increased lipid peroxidation and reactive oxygen species (ROS) generation, depleted glutathione (GSH), and decreased superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione reductase (GR) activities. Acetaminophen caused exacerbation of arsenic-mediated lipid peroxidation and ROS generation and further enhancement of serum alanine aminotransferase and aspartate aminotransferase activities. In Phase-I, acetaminophen caused further GSH depletion and reduction in SOD, catalase, GPx and GR activities, but in Phase-II, only GPx and GR activities were more affected. Arsenic did not alter basal and inducible nitric oxide synthase (iNOS)-mediated NO production, but decreased constitutive NOS (cNOS)-mediated NO release. Arsenic reduced expression of endothelial NOS (eNOS) and iNOS genes. Acetaminophen up-regulated eNOS and iNOS expression and NO production in Phase-I, but reversed these effects in Phase-II. Results reveal that acetaminophen increased the risk of arsenic-mediated hepatic oxidative damage. Withdrawal of acetaminophen administration also increased susceptibility of liver to hepatotoxicity. Both ROS and NO appeared to mediate lipid peroxidation in Phase-I, whereas only ROS appeared responsible for peroxidative damage in Phase-II. PMID:22120977

  2. Cytochrome P450 2E1 inhibition prevents hepatic carcinogenesis induced by diethylnitrosamine in alcohol-fed rats.

    PubMed

    Ye, Qinyuan; Lian, Fuzhi; Chavez, Pollyanna R G; Chung, Jayong; Ling, Wenhua; Qin, Hua; Seitz, Helmut K; Wang, Xiang-Dong

    2012-12-01

    Chronic alcohol ingestion increases hepatic cytochrome P450 2E1 (CYP2E1), which is associated with hepatocarcinogenesis. We investigated whether treatment with chlormethiazole (CMZ), a CYP2E1 inhibitor, protects against alcohol-associated hepatic carcinogenesis in rats. Rats were fed either an ethanol liquid diet or a non-ethanol liquid diet, with or without CMZ for one and ten months. A single intraperitoneal injection of diethylnitrosamine (DEN, 20 mg/kg) was given to initiate hepatic carcinogenesis. CYP2E1 expression, inflammatory proteins, cell proliferation, protein-bound 4-HNE, etheno-DNA adducts, 8-hydroxy-2'-deoxyguanosine (8-OHdG), retinoid concentrations, and hepatic carcinogenesis were examined. Ethanol feeding for 1 month with DEN resulted in significantly increased hepatic CYP2E1 levels and increased nuclear accumulation of NF-?B protein and TNF-? expression, which were associated with increased cyclin D1 expression and p-GST positive altered hepatic foci. All of these changes induced by ethanol feeding were significantly inhibited by the one month CMZ treatment. At 10-months of treatment, hepatocellular adenomas were detected in ethanol-fed rats only, but neither in control rats nor in animals receiving ethanol and CMZ. The 8-OHdG formation was found to be significantly increased in ethanol fed animals and normalized with CMZ treatment. In addition, alcohol-reduced hepatic retinol and retinoic acid concentrations were restored by CMZ treatment to normal levels in the rats at 10 months of treatment. These data demonstrate that the inhibition of ethanol-induced CYP2E1 as a key pathogenic factor can counteract the tumor-promoting action of ethanol by decreasing TNF-? expression, NF-?B activation, and oxidative DNA damage as well as restoring normal hepatic levels of retinoic acid in DEN-treated rats. PMID:23543859

  3. Gastroprotective effect of crocin in ethanol-induced gastric injury in rats.

    PubMed

    El-Maraghy, Shohda A; Rizk, Sherine M; Shahin, Nancy N

    2015-03-01

    The present study investigated the gastroprotective effect of crocin in ethanol-induced gastric injury in rats. Rats were allocated into a normal group, an ulcer group, a crocin-treated group, an ulcer group pretreated with crocin, and an ulcer group pretreated with omeprazole as a reference anti-ulcer drug. Rats were sacrificed 3h after ethanol administration. Prophylactic administration of crocin (50mg/kg/day, i.p.) for 3 consecutive days before the administration of 70% ethanol (10 ml/kg, orally) resulted in significant gastroprotection compared to ethanol-ulcerated rats as manifested by significant reduction in the gastric ulcer index. Crocin pretreatment increased ethanol-lowered levels of gastric juice mucin and mucosal prostaglandin E2 (PGE2) and interleukin-6 (IL-6). Moreover, crocin significantly decreased ethanol-elevated tumor necrosis factor-alpha (TNF-?) level, myeloperoxidase activity and heat shock protein 70 mRNA and protein levels. It also restored ethanol-altered mucosal levels of glutathione, malondialdehyde and superoxide dismutase activity. Furthermore, crocin-pretreatment alleviated ethanol-induced mucosal apoptosis as revealed by significant down-regulation of cytochrome c and caspase-3 mRNA expression, significant decrease in caspase-3 activity and mitigated DNA fragmentation as indicated by significant decrements in comet parameters. The protective efficacy of crocin was further supported by histological assessment. No significant difference was observed between crocin and omeprazole (20mg/kg orally 1h before ethanol administration) regarding their mucin-secretagogue and antioxidant effects, as well as their effects on TNF-?, IL-6 and cytochrome c. On the other hand, omeprazole was superior in enhancing PGE2 level and in alleviating neutrophil infiltration, caspase-3 activation and DNA fragmentation. Conclusively, crocin protects rat gastric mucosa against ethanol-induced injury via anti-inflammatory, anti-oxidative, anti-apoptotic and mucin-secretagogue mechanisms that are probably mediated by enhanced PGE2 release. PMID:25637687

  4. PKC? contributes to chronic ethanol-induced steatosis in mice but not inflammation and necrosis

    PubMed Central

    Kaiser, J. Phillip; Guo, Luping; Beier, Juliane I.; Zhang, Jun; Bhatnagar, Aruni; Arteel, Gavin E.

    2013-01-01

    Background/Aims Protein kinase c-epsilon (PKC?) has been shown to play a role in experimental steatosis by acute alcohol. The 'two-hit' hypothesis implies that preventing steatosis should blunt more advanced liver damage (e.g., inflammation and necrosis). However, the role of PKC? in these pathologies is not yet known. The goal of this current work was to address this question in a model of chronic alcohol exposure using antisense oligonucleotides (ASO) against PKC?. Methods Accordingly, PKC? ASO- and saline-treated mice were fed high-fat control or ethanol-containing enteral diets for 4 weeks. Results Chronic ethanol exposure significantly elevated hepatic lipid pools as well as activated PKC?. The PKC? ASO partially blunted the increases in hepatic lipids caused by ethanol. Administration of PKC? ASO also completely prevented the increase in the expression of fatty acid synthase (FAS) and TNF? caused by ethanol. Despite these protective effects, the PKC? ASO was unable to prevent the increases in inflammation and necrosis caused by chronic ethanol. These latter results correlated with an inability of the PKC? ASO to blunt the upregulation of plasminogen activator inhibitor-1 (PAI-1) and the accumulation of fibrin. Importantly, PAI-1 has been previously shown to more robustly mediate inflammation and necrosis (versus steatosis) after chronic ethanol exposure. Conclusions This study identifies a novel potential mechanism where ethanol, independent of steatosis, can contribute to liver damage. These results also suggest that PAI-1 and fibrin accumulation may be at the center of this PKC?-independent pathway. PMID:24483773

  5. Blockade of store-operated calcium entry alleviates ethanol-induced hepatotoxicity via inhibiting apoptosis.

    PubMed

    Cui, Ruibing; Yan, Lihui; Luo, Zheng; Guo, Xiaolan; Yan, Ming

    2015-08-15

    Extracellular Ca(2+) influx has been suggested to play a role in ethanol-induced hepatocyte apoptosis and necrosis. Previous studies indicated that store-operated Ca(2+) entry (SOCE) was involved in liver injury induced by ethanol in HepG2 cells. However, the mechanisms underlying liver injury caused by SOCE remain unclear. We aimed to investigate the effects and mechanism of SOCE inhibition on liver injury induced by ethanol in BRL cells and Sprague-Dawley rats. Our data demonstrated that ethanol (0-400mM) dose-dependently increased hepatocyte injury and 100mM ethanol significantly upregulated the mRNA and protein expression of SOC for at least 72h in BRL cells. Blockade of SOCE by pharmacological inhibitors and sh-RNA knockdown of STIM1 and Orai1 attenuated intracellular Ca(2+) overload, restored the mitochondrial membrane potential (MMP), decreased cytochrome C release and inhibited ethanol-induced apoptosis. STIM1 and Orai1 expression was greater in ethanol-treated than control rats, and the SOCE inhibitor corosolic acid ameliorated the histopathological findings and alanine transaminase and aspartate transaminase activity as well as decreased cytochrome C release and inhibited alcohol-induced cell apoptosis. These findings suggest that SOCE blockade could alleviate alcohol-induced hepatotoxicity via inhibiting apoptosis. SOCE might be a useful therapeutic target in alcoholic liver diseases. PMID:26033013

  6. Suppression of ethanol-induced cardiac hypertrophy by beta-adrenoceptor blockade.

    PubMed

    King, D C; Hirst, M

    1990-05-01

    The effects of D,L-propranolol and its resolved epimers on cardiac size in rats given ethanol, or a control diet containing maltose-dextrin, every 8 h by gavage, for 48 h were assessed. Co-treatment with ethanol plus saline for 48 h resulted in increases of approximately 10% in wet and dry heart weights, and in their proportional measures (g/kg body wt). Cardiac protein content was increased similarly. Administration of D,L-propranolol (10, 20 mg/kg), or L-propranolol (5, 10, 20 mg/kg), suppressed the increases in response to ethanol, D-Propranolol (10, 20 mg/kg) was ineffective in attenuating ethanol-induced increases in heart weights and protein content. Values of total cardiac DNA and fractional water content were unaffected by any of the treatments. Adrenaline and noradrenaline levels in urine were elevated during 48 h of intoxication in all rats given ethanol. The results suggest that severe, subacute intoxication with ethanol induces cardiac hypertrophy. Further, the data implies that the hypertrophy is mediated through activation of cardiac beta-adrenoceptors. PMID:1974932

  7. A Novel Antioxidant Multitarget Iron Chelator M30 Protects Hepatocytes against Ethanol-Induced Injury

    PubMed Central

    Lv, Yi; Lin, Bin; Tipoe, George L.; Youdim, Moussa B. H.; Xing, Feiyue; Liu, Yingxia

    2015-01-01

    The multitarget iron chelator, M30, is a novel antioxidant and protective agent against oxidative stress in a spectrum of diseases. However, there is no report regarding its role in liver diseases. Since oxidative stress is one of the major pathological events during the progression of alcoholic liver diseases, the protective effects and mechanisms of M30 on ethanol-induced hepatocyte injury were investigated in this study. Rat hepatocyte line BRL-3A was pretreated with M30 prior to ethanol treatment. Cell death, apoptosis, oxidative stress, and inflammation were examined. Specific antagonists and agonists were applied to determine the involvements of hypoxia inducible factor-1 alpha (HIF-1?) and its upstream adenylate cyclase (AC)/cyclic AMP (cAMP)/protein kinase A (PKA)/HIF-1?/NOD-like receptor 3 (NLRP3) inflammasome pathway. We found that M30 significantly attenuated ethanol-induced cellular death, apoptosis, production of reactive oxygen species (ROS), and secretion of inflammatory cytokines and inhibited activation of the AC/cAMP/PKA/HIF-1?/NLRP3 inflammasome pathway. Inhibition and activation of the AC/cAMP/PKA/HIF-1? pathway mimicked and abolished the effects of M30, respectively. In conclusion, inhibition of the AC/cAMP/PKA/HIF-1?/NLRP3 inflammasome pathway by M30 partially contributes to its attenuation of hepatocyte injury caused by ethanol exposure. PMID:25722794

  8. Gastroprotective activity of Annona muricata leaves against ethanol-induced gastric injury in rats via Hsp70/Bax involvement

    PubMed Central

    Moghadamtousi, Soheil Zorofchian; Rouhollahi, Elham; Karimian, Hamed; Fadaeinasab, Mehran; Abdulla, Mahmood Ameen; Kadir, Habsah Abdul

    2014-01-01

    The popular fruit tree of Annona muricata L. (Annonaceae), known as soursop and graviola, is a widely distributed plant in Central and South America and tropical countries. Leaves of A. muricata have been reported to possess antioxidant and anti-inflammatory activities. In this study, the gastroprotective effects of ethyl acetate extract of A. muricata leaves (EEAM) were investigated against ethanol-induced gastric injury models in rats. The acute toxicity test of EEAM in rats, carried out in two doses of 1 g/kg and 2 g/kg, showed the safety of this plant, even at the highest dose of 2 g/kg. The antiulcer study in rats (five groups, n=6) was performed with two doses of EEAM (200 mg/kg and 400 mg/kg) and with omeprazole (20 mg/kg), as a standard antiulcer drug. Gross and histological features showed the antiulcerogenic characterizations of EEAM. There was significant suppression on the ulcer lesion index of rats pretreated with EEAM, which was comparable to the omeprazole effect in the omeprazole control group. Oral administration of EEAM to rats caused a significant increase in the level of nitric oxide and antioxidant activities, including catalase, glutathione, and superoxide dismutase associated with attenuation in gastric acidity, and compensatory effect on the loss of gastric wall mucus. In addition, pretreatment of rats with EEAM caused significant reduction in the level of malondialdehyde, as a marker for oxidative stress, associated with an increase in prostaglandin E2 activity. Immunohistochemical staining also demonstrated that EEAM induced the downregulation of Bax and upregulation of Hsp70 proteins after pretreatment. Collectively, the present results suggest that EEAM has a promising antiulcer potential, which could be attributed to its suppressive effect against oxidative damage and preservative effect toward gastric wall mucus. PMID:25378912

  9. Hepatoprotective potential of Lavandula coronopifolia extracts against ethanol induced oxidative stress-mediated cytotoxicity in HepG2 cells.

    PubMed

    Farshori, Nida Nayyar; Al-Sheddi, Ebtsam S; Al-Oqail, Mai M; Hassan, Wafaa H B; Al-Khedhairy, Abdulaziz A; Musarrat, Javed; Siddiqui, Maqsood A

    2013-03-28

    The present investigations were carried out to study the protective potential of four extracts (namely petroleum ether extract (LCR), chloroform extract (LCM), ethyl acetate extract (LCE), and alcoholic extract (LCL)) of Lavandula coronopifolia on oxidative stress-mediated cell death induced by ethanol, a known hepatotoxin in human hapatocellular carcinoma (HepG2) cells. Cells were pretreated with LCR, LCM, LCE, and LCL extracts (10-50 ?g/ml) of L. coronopifolia for 24 h and then ethanol was added and incubated further for 24 h. After the exposure, cell viability using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and neutral red uptake assays and morphological changes in HepG2 cells were studied. Pretreatment with various extracts of L. coronpifolia was found to be significantly effective in countering the cytotoxic responses of ethanol. Antioxidant properties of these L. coronopifolia extracts against reactive oxygen species (ROS) generation, lipid peroxidation (LPO), and glutathione (GSH) levels induced by ethanol were investigated. Results show that pretreatment with these extracts for 24 h significantly inhibited ROS generation and LPO induced and increased the GSH levels reduced by ethanol. The data from the study suggests that LCR, LCM, LCE, and LCL extracts of L. coronopifolia showed hepatoprotective activity against ethanol-induced damage in HepG2 cells. However, a comparative study revealed that the LCE extract was found to be the most effective and LCL the least effective. The hepatoprotective effects observed in the study could be associated with the antioxidant properties of these extracts of L. coronopifolia. PMID:23546397

  10. Prenatal ethanol exposure alters ethanol-induced Fos immunoreactivity and dopaminergic activity in the mesocorticolimbic pathway of the adolescent brain.

    PubMed

    Fabio, M C; Vivas, L M; Pautassi, R M

    2015-08-20

    Prenatal ethanol exposure (PEE) promotes alcohol intake during adolescence, as shown in clinical and pre-clinical animal models. The mechanisms underlying this effect of prenatal ethanol exposure on postnatal ethanol intake remain, however, mostly unknown. Few studies assessed the effects of moderate doses of prenatal ethanol on spontaneous and ethanol-induced brain activity on adolescence. This study measured, in adolescent (female) Wistar rats prenatally exposed to ethanol (0.0 or 2.0g/kg/day, gestational days 17-20) or non-manipulated (NM group) throughout pregnancy, baseline and ethanol-induced cathecolaminergic activity (i.e., colocalization of c-Fos and tyrosine hydroxylase) in ventral tegmental area (VTA), and baseline and ethanol-induced Fos immunoreactivity (ir) in nucleus accumbens shell and core (AcbSh and AcbC, respectively) and prelimbic (PrL) and infralimbic (IL) prefrontal cortex. The rats were challenged with ethanol (dose: 0.0, 1.25, 2.5 or 3.25g/kg, i.p.) at postnatal day 37. Rats exposed to vehicle prenatally (VE group) exhibited reduced baseline dopaminergic tone in VTA; an effect that was inhibited by prenatal ethanol exposure (PEE group). Dopaminergic activity in VTA after the postnatal ethanol challenge was greater in PEE than in VE or NM animals. Ethanol-induced Fos-ir at AcbSh was found after 1.25g/kg and 2.5g/kg ethanol, in VE and PEE rats, respectively. PEE did not alter ethanol-induced Fos-ir at IL but reduced ethanol-induced Fos-ir at PrL. These results suggest that prenatal ethanol exposure heightens dopaminergic activity in the VTA and alters the response of the mesocorticolimbic pathway to postnatal ethanol exposure. These effects may underlie the enhanced vulnerability to develop alcohol-use disorders of adolescents with a history of in utero ethanol exposure. PMID:26057446

  11. 1,2-DIBROMOETHANE CAUSES RAT HEPATIC DNA DAMAGE AT LOW DOSES

    EPA Science Inventory

    Two oral administrations of 1,2-dibromoethane to adult female rats at doses above 10 micromoles/kg (1.9 mg/kg) caused DNA damage as determined by the alkaline elution technique. Far greater doses (300 micromoles/kg, 56.4 mg/kg) of 1,2-dibromoethane were required to cause other he...

  12. Hepatoprotective potential of chestnut bee pollen on carbon tetrachloride-induced hepatic damages in rats.

    PubMed

    Y?ld?z, Oktay; Can, Zehra; Saral, Ozlem; Yulu?, Esin; Oztürk, Ferhat; Aliyaz?c?o?lu, Rezzan; Canpolat, Sinan; Kolayl?, Sevgi

    2013-01-01

    Bee pollen has been used as an apitherapy agent for several centuries to treat burns, wounds, gastrointestinal disorders, and various other diseases. The aim of our study was to investigate the hepatoprotective effects of chestnut bee pollen against carbon tetrachloride (CCI4)-induced liver damage. Total phenolic content, flavonoid, ferric reducing/antioxidant power, and DPPH radical activity measurements were used as antioxidant capacity determinants of the pollen. The study was conducted in rats as seven groups. Two different concentrations of chestnut bee pollens (200 and 400?mg/kg/day) were given orally and one group was administered with silibinin (50?mg/kg/day, i.p.) for seven days to the rats following the CCI4 treatment. The protective effect of the bee pollen was monitored by aspartate transaminase (AST) and alanine transaminase (AST) activities, histopathological imaging, and antioxidant parameters from the blood and liver samples of the rats. The results were compared with the silibinin-treated and untreated groups. We detected that CCI4 treatment induced liver damage and both the bee pollen and silibinin-treated groups reversed the damage; however, silibinin caused significant weight loss and mortality due, severe diarrhea in the rats. The chestnut pollen had showed 28.87?mg GAE/g DW of total phenolic substance, 8.07?mg QUE/g DW of total flavonoid, 92.71?mg Cyn-3-glu/kg DW of total anthocyanins, and 9?mg ? -carotene/100?g DW of total carotenoid and substantial amount of antioxidant power according to FRAP and DPPH activity. The results demonstrated that the chestnut bee pollen protects the hepatocytes from the oxidative stress and promotes the healing of the liver damage induced by CCI4 toxicity. Our findings suggest that chestnut bee pollen can be used as a safe alternative to the silibinin in the treatment of liver injuries. PMID:24250716

  13. Combination of Alcohol and Fructose Exacerbates Metabolic Imbalance in Terms of Hepatic Damage, Dyslipidemia, and Insulin Resistance in Rats

    PubMed Central

    Schultze, Frank Christian; Wilting, Jörg; Mihm, Sabine; Raddatz, Dirk; Ramadori, Giuliano

    2014-01-01

    Although both alcohol and fructose are particularly steatogenic, their long-term effect in the development of a metabolic syndrome has not been studied in vivo. Consumption of fructose generally leads to obesity, whereas ethanol can induce liver damage in the absence of overweight. Here, Sprague-Dawley rats were fed ad libitum for 28 days on five diets: chow (control), liquid Lieber-DeCarli (LDC) diet, LDC +30%J of ethanol (L-Et) or fructose (L-Fr), and LDC combined with 30%J ethanol and 30%J fructose (L-EF). Body weight (BW) and liver weight (LW) were measured. Blood and liver samples were harvested and subjected to biochemical tests, histopathological examinations, and RT-PCR. Alcohol-containing diets substantially reduced the food intake and BW (?3rd week), whereas fructose-fed animals had higher LW than controls (P<0.05). Additionally, leukocytes, plasma AST and leptin levels were the highest in the fructose-administered rats. Compared to the chow and LDC diets, the L-EF diet significantly elevated blood glucose, insulin, and total-cholesterol levels (also vs. the L-Et group). The albumin and Quick-test levels were the lowest, whereas ALT activity was the highest in the L-EF group. Moreover, the L-EF diet aggravated plasma triglyceride and reduced HDL-cholesterol levels more than 2.7-fold compared to the sum of the effects of the L-Et and L-Fr diets. The decreased hepatic insulin clearance in the L-EF group vs. control and LDC groups was reflected by a significantly decreased C-peptide:insulin ratio. All diets except the control caused hepatosteatosis, as evidenced by Nile red and H&E staining. Hepatic transcription of insulin receptor substrate-1/2 was mainly suppressed by the L-Fr and L-EF diets. The L-EF diet did not enhance the mitochondrial ?-oxidation of fatty acids (Cpt1? and Ppar-? expressions) compared to the L-Et or L-Fr diet. Together, our data provide evidence for the coaction of ethanol and fructose with a high-fat-diet on dyslipidemia and insulin resistance-accompanied liver damage. PMID:25101998

  14. Xanthohumol, a main prenylated chalcone from hops, reduces liver damage and modulates oxidative reaction and apoptosis in hepatitis C virus infected Tupaia belangeri.

    PubMed

    Yang, Mingbo; Li, Na; Li, Fang; Zhu, Qianqian; Liu, Xi; Han, Qunying; Wang, Yawen; Chen, Yanping; Zeng, Xiaoyan; Lv, Yi; Zhang, Pingping; Yang, Cuiling; Liu, Zhengwen

    2013-08-01

    Hepatitis C virus (HCV) infection in Tupaia belangeri (Tupaia) represents an important model of HCV infection. Xanthohumol (XN), a major prenylated chalcone from hops, has various biological activities including hepatopreventive and anti-viral activities. In this study, Tupaias infected with HCV RNA positive serum were used to evaluate the effects of XN on liver damage, oxidative reaction, apoptosis and viral protein expression in liver tissues. The Tupaias inoculated with HCV positive serum had elevated serum aminotransferase levels and inflammation, especially hepatic steatosis, and HCV core protein expression in liver tissue. In the animals inoculated with HCV positive serum, XN significantly decreased aminotransferase levels, histological activity index, hepatic steatosis score and transforming growth factor ?1 expression in liver tissue compared with the animals without XN intervention. XN reduced HCV core protein expression in liver tissue compared with those without XN intervention but the difference was not significant. XN significantly decreased malondialdehyde, potentiated superoxide dismutase and glutathione peroxidase, reduced Bax expression, promoted Bcl-xL and inhibited caspase 3 activity in liver tissues compared with the animals without XN intervention. These results indicate that XN may effectively improve hepatic inflammation, steatosis and fibrosis induced by HCV in Tupaias primarily through inhibition of oxidative reaction and regulation of apoptosis and possible suppression of hepatic stellate cell activation. The anti-HCV potential of XN needs further investigation. PMID:23669332

  15. Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity

    Microsoft Academic Search

    Luigi E. Adinolfi; Michele Gambardella; Augusto Andreana; Marie-françoise Tripodi; Riccardo Utili; Giuseppe Ruggiero

    2001-01-01

    The role of steatosis in the progression of liver damage in chronic hepatitis C (CHC) was studied. Enrolled were 180 consecutive liver biopsy-proven CHC patients and 41 additional subjects with a known duration of infection. We evaluated the histological activity index (HAI), grade of fibrosis and steatosis, body mass index (BMI; kg\\/m2), distribution of body fat, HCV genotype, and levels

  16. Inhibitive effect of cordyceps sinensis on experimental hepatic fibrosis and its possible mechanism

    Microsoft Academic Search

    Yu-Kan Liu; Wei Shen

    2003-01-01

    AIM: To investigate the inhibitive effect and its possible mechanism of Cordyceps Sinensis (CS) on CCl4-plus ethanol- induced hepatic fibrogenesis in experimental rats. METHODS: Rats were randomly allocated into a normal control group, a model control group and a CS group. The latter two groups were administered with CCl4 and ethanol solution at the beginning of the experiment to induce

  17. In vivo gastroprotective effects of five Turkish folk remedies against ethanol-induced lesions.

    PubMed

    Gürbüz, Ilhan; Ustün, Osman; Ye?ilada, Erdem; Sezik, Ekrem; Akyürek, Nalan

    2002-12-01

    Through evaluation of the data accumulated in Data Bank of Turkish Folk Remedies (TUHIB), five plant remedies, which are used to treat stomach ache were selected to test for their anti-ulcerogenic potency. In order to confirm the claimed activities, either decoction or methanol extracts were prepared from the roots of Asphodelus aestivus and Cichorium intybus, herbs of Equisetum palustre and Viscum album ssp. album and fruits of Laurus nobilis, according to their folkloric application way and tested for their effects on ethanol-induced gastric ulcer model in rats. Pharmacological experiments clearly demonstrated that the relevant extracts of all the plants given orally showed significant stomach protection against this model of ulcerogenesis. Results were further evaluated by using histopathological techniques. PMID:12426092

  18. Nelumbo nucifera leaves protect hydrogen peroxide-induced hepatic damage via antioxidant enzymes and HO-1/Nrf2 activation.

    PubMed

    Je, Jae-Young; Lee, Da-Bin

    2015-06-10

    Naturally occurring phenolic compounds are widely found in plants. Here, the phenolic composition and hepatoprotective effect of the butanolic extract (BE) from Nelumbo nucifera leaves against H2O2-induced hepatic damage in cultured hepatocytes were investigated. BE showed high total phenol and flavonoid contents, and major phenolic compounds are quercetin, catechin, ferulic acid, rutin, and protocatechuic acid by HPLC analysis. BE effectively scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis(3-ethylbenzthiazoline)-6-sulfonic acid (ABTS) cation radicals (IC50 values of 5.21 ?g mL(-1) for DPPH and 6.22 ?g mL(-1) for ABTS(+)) and showed strong reducing power. Pretreatment of BE prior to 650 ?M H2O2 exposure markedly increased cell viability and suppressed H2O2-induced intracellular reactive oxygen species generation and AAPH-induced cell membrane lipid peroxidation. In addition, BE up-regulated intracellular glutathione levels under normal and oxidative stress conditions. Notably, the hepatoprotective effect of BE was directly correlated with the increased expression of superoxide dismutase-1 (SOD-1) by 0.62-fold, catalase (CAT) by 0.42-fold, and heme oxygenase-1 (HO-1) by 2.4-fold. Pretreatment of BE also increased the nuclear accumulation of Nrf2 by 8.1-fold indicating that increased SOD-1, CAT, and HO-1 expressions are Nrf2-mediated. PMID:25962859

  19. SELECTIVE VULNERABILITY OF EMBRYONIC CELL POPULATIONS TO ETHANOL-INDUCED APOPTOSIS: IMPLICATIONS FOR ALCOHOL RELATED BIRTH DEFECTS AND NEURODEVELOPMENTAL DISORDER

    EPA Science Inventory

    The locations of cell death and resulting malformations in embryos following teratogen exposure vary depending on the teratogen used, the genotype of the conceptus, and the developmental stage of the embryo at time of exposure. To date, ethanol-induced cell death has been charac...

  20. LIMB DEFECTS INDUCED BY RETINOIC ACID SIGNALING ANTAGONISM AND SYNTHESIS INHIBITION ARE CONSISTENT WITH ETHANOL-INDUCED LIMB DEFECTS

    EPA Science Inventory

    Limb defects induced by retinoic acid signaling antagonism and synthesis inhibition are consistent with ethanol-induced limb defects Johnson CS1, Sulik KK1,2, Hunter, ES III3 1Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, NC....

  1. Ethanol-induced alterations in lipid composition of Saccharomyces cerevisiae in the presence of exogenous fatty acid

    Microsoft Academic Search

    Haruhiko Mizoguchi; Shodo Hara

    1997-01-01

    Ethanol-induced alterations in the lipid composition of Saccharomyces cerevisiae grown in the presence of exogenous fatty acids were studied. The addition of both palmitic acid and ethanol (4–8%) to the basal medium resulted in a striking increase in the palmitic acid content and decreases in the content of myristoleic, palmitoleic, and oleic acids in the phospholipid fatty acid composition, compared

  2. Ameliorative efficacy of tetrahydrocurcumin against arsenic induced oxidative damage, dyslipidemia and hepatic mitochondrial toxicity in rats.

    PubMed

    Muthumani, M; Miltonprabu, S

    2015-06-25

    Arsenic (As) is a well-known human carcinogen and a potent hepatotoxin. Environmental exposure to arsenic imposes a serious health hazard to humans and other animals worldwide. Tetrahydrocurcumin (THC), one of the major metabolites of curcumin, exhibits many of the same physiological and pharmacological activities as curcumin and in some systems may exert greater antioxidant activity than the curcumin. It has been reported that THC has antioxidant efficacy attributable to the presence of identical ?-diketone of 3rd and 5th substitution in heptane moiety. In the present study, rats were orally treated with arsenic alone (5mgkg(-1)bw/day) with THC (80mgkg(-1)bw/day) for 28days. Hepatotoxicity was measured by the increased activities of serum hepatospecific enzymes, namely aspartate transaminase, alanine transaminase, alkaline phosphatase and bilirubin along with increased elevation of lipid peroxidative markers, thiobarbituric acid reactive substances. And also elevated levels of serum cholesterol, triglycerides, free fatty acids and phospholipids were observed in arsenic intoxicated rats. These effects of arsenic were coupled with enhanced mitochondrial swelling, inhibition of cytochrome c oxidase, Ca(2+)ATPase and a decrease in mitochondrial calcium content. The toxic effect of arsenic was also indicated by significantly decreased activities of enzymatic antioxidants such as superoxide dismutase, catalase, and glutathione peroxidase along with non-enzymatic antioxidant such as reduced glutathione. Administration of THC exhibited significant reversal of arsenic induced toxicity in hepatic tissue. All these changes were supported by the reduction of arsenic concentration and histopathological observations of the liver. These results suggest that THC has a protective effect over arsenic induced toxicity in rat. PMID:25869292

  3. Comparison of cannabidiol, antioxidants, and diuretics in reversing binge ethanol-induced neurotoxicity.

    PubMed

    Hamelink, Carol; Hampson, Aidan; Wink, David A; Eiden, Lee E; Eskay, Robert L

    2005-08-01

    Binge alcohol consumption in the rat induces substantial neurodegeneration in the hippocampus and entorhinal cortex. Oxidative stress and cytotoxic edema have both been shown to be involved in such neurotoxicity, whereas N-methyl-d-aspartate (NMDA) receptor activity has been implicated in alcohol withdrawal and excitoxic injury. Because the nonpsychoactive cannabinoid cannabidiol (CBD) was previously shown in vitro to prevent glutamate toxicity through its ability to reduce oxidative stress, we evaluated CBD as a neuroprotectant in a rat binge ethanol model. When administered concurrently with binge ethanol exposure, CBD protected against hippocampal and entorhinal cortical neurodegeneration in a dose-dependent manner. Similarly, the common antioxidants butylated hydroxytoluene and alpha-tocopherol also afforded significant protection. In contrast, the NMDA receptor antagonists dizocilpine (MK-801) and memantine did not prevent cell death. Of the diuretics tested, furosemide was protective, whereas the other two anion exchanger inhibitors, L-644,711 [(R)-(+)-(5,6-dichloro2,3,9,9a-tetrahydro 3-oxo-9a-propyl-1H-fluoren-7-yl)oxy acetic acid] and bumetanide, were ineffective. In vitro comparison of these diuretics indicated that furosemide is also a potent antioxidant, whereas the nonprotective diuretics are not. The lack of efficacy of L-644,711 and bumetanide suggests that the antioxidant rather than the diuretic properties of furosemide contribute most critically to its efficacy in reversing ethanol-induced neurotoxicity in vitro, in our model. This study provides the first demonstration of CBD as an in vivo neuroprotectant and shows the efficacy of lipophilic antioxidants in preventing binge ethanol-induced brain injury. PMID:15878999

  4. Association between Noninvasive Fibrosis Markers and Cardio-Vascular Organ Damage among Adults with Hepatic Steatosis

    PubMed Central

    Sesti, Giorgio; Sciacqua, Angela; Fiorentino, Teresa Vanessa; Perticone, Maria; Succurro, Elena; Perticone, Francesco

    2014-01-01

    Evidence suggests that advanced fibrosis, as determined by the noninvasive NAFLD fibrosis score (NFS), is a predictor of cardiovascular mortality in individuals with ultrasonography-diagnosed NAFLD. Whether the severity of histology (i.e., fibrosis stage) is associated with more pronounced cardiovascular organ damage is unsettled. In this study, we analyzed the clinical utility of NFS in assessing increased carotid intima-media thickness (cIMT), and left ventricular mass index (LVMI). In this cross-sectional study NFS, cIMT and LVMI were assessed in 400 individuals with ultrasonography-diagnosed steatosis. As compared with individuals at low probability of liver fibrosis, individuals both at high and at intermediate probability of fibrosis showed an unfavorable cardio-metabolic risk profile having significantly higher values of waist circumference, insulin resistance, high sensitivity C-reactive protein (hsCRP), fibrinogen, cIMT, and LVMI, and lower insulin-like growth factor-1 (IGF-1) levels. The differences in cIMT and LVMI remained significant after adjustment for smoking and metabolic syndrome. In a logistic regression model adjusted for age, gender, smoking, and diagnosis of metabolic syndrome, individuals at high probability of fibrosis had a 3.9-fold increased risk of vascular atherosclerosis, defined as cIMT>0.9 mm, (OR 3.95, 95% CI 1.12–13.87) as compared with individuals at low probability of fibrosis. Individuals at high probability of fibrosis had a 3.5-fold increased risk of left ventricular hypertrophy (LVH) (OR 3.55, 95% CI 1.22–10.34) as compared with individuals at low probability of fibrosis. In conclusion, advanced fibrosis, determined by noninvasive fibrosis markers, is associated with cardiovascular organ damage independent of other known factors. PMID:25111713

  5. Cytisine modulates chronic voluntary ethanol consumption and ethanol-induced striatal up-regulation of ?FosB in mice.

    PubMed

    Sajja, Ravi Kiran; Rahman, Shafiqur

    2013-06-01

    Chronic administration of ethanol induces persistent accumulation of ?FosB, an important transcription factor, in the midbrain dopamine system. This process underlies the progression to addiction. Previously, we have shown that cytisine, a neuronal nicotinic acetylcholine receptor (nAChR) partial agonist, reduces various ethanol-drinking behaviors and ethanol-induced striatal dopamine function. However, the effects of cytisine on chronic ethanol drinking and ethanol-induced up-regulation of striatal ?FosB are not known. Therefore, we examined the effects of cytisine on chronic voluntary ethanol consumption and associated striatal ?FosB up-regulation in C57BL/6J mice using behavioral and biochemical methods. Following the chronic voluntary consumption of 15% (v/v) ethanol under a 24-h two-bottle choice intermittent access (IA; 3 sessions/week) or continuous access (CA; 24 h/d and 7 d/week) paradigm, mice received repeated intraperitoneal injections of saline or cytisine (0.5 or 3.0 mg/kg). Ethanol and water intake were monitored for 24 h post-treatment. Pretreatment with cytisine (0.5 or 1.5 mg/kg) significantly reduced ethanol consumption and preference in both paradigms at 2 h and 24 h post-treatment. The ?FosB levels in the ventral and dorsal striatum were determined by Western blotting 18-24 h after the last point of ethanol access. In addition, cytisine (0.5 mg/kg) significantly attenuated up-regulation of ?FosB in the ventral and dorsal striatum following chronic ethanol consumption in IA and CA paradigms. The results indicate that cytisine modulates chronic voluntary ethanol consumption and reduces ethanol-induced up-regulation of striatal ?FosB. Further, the data suggest a critical role of nAChRs in chronic ethanol-induced neurochemical adaptations associated with ethanol addiction. PMID:23601929

  6. Comparative effects of endrin on hepatic lipid peroxidation and DNA damage, and nitric oxide production by peritoneal macrophages from C57BL/6J and DBA/2 mice.

    PubMed

    Bagchi, M; Hassoun, E; Akubue, P; Bagchi, D; Stohs, S J

    1993-07-01

    1. Endrin is a polyhalogenated cyclic hydrocarbon which produces hepatic and neurologic toxicity. In order to further assess the mechanism of toxicity of endrin, the dose-dependent effects of endrin on hepatic lipid peroxidation and DNA damage, and nitric oxide (NO) production by peritoneal exudate cells (primarily macrophages) were investigated in C57BL/6J and DBA/2 mice which vary at the Ah receptor genetic locus. C57BL/6J mice are dioxin-responsive, while DBA/2 mice are dioxin-insensitive. 2. Mice of both strains were treated with 0, 1, 2 or 4 mg endrin kg-1 as a single oral dose in corn oil, and the animals were killed 24 hr post-treatment. At doses of 1, 2 and 4 mg endrin kg-1 in C57BL/6J mice, hepatic mitochondrial lipid peroxidation increased 1.2-, 2.2- and 3.2-fold, respectively, and 1.8-, 2.3- and 3.5-fold with microsomes, respectively. At these same doses in DBA/2 mice, hepatic mitochondrial lipid peroxidation increased 1.3-, 2.0- and 2.6-fold, respectively, and 1.5-, 1.9- and 2.5-fold with microsomes, respectively. 3. Increases of 2.3-, 2.4- and 4.9-fold were observed in hepatic DNA damage (elution constants) in C57BL/6J mice at doses of 1, 2 and 4 mg endrin kg-1, respectively, while at these same three doses, increases of 1.9-, 2.1- and 2.3-fold were observed for DBA/2 mice, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7900971

  7. Evaluation of antiglypican-3 therapy as a promising target for amelioration of hepatic tissue damage in hepatocellular carcinoma.

    PubMed

    Zaghloul, Randa A; El-Shishtawy, Mamdouh M; El Galil, Khaled H Abd; Ebrahim, Mohamed A; Metwaly, AbdelHamid A; Al-Gayyar, Mohammed M

    2015-01-01

    In Egypt, hepatocellular carcinoma (HCC) was predicted to continue to rise over the next few decades causing a national problem. Meanwhile, glypican-3 (GPC3), a highly expressed glypican, has emerged as a potential target for HCC immunotherapy. Therefore, we aimed to identify the impact of blocking GPC3 on liver damage in HCC as well as a possible mechanism. Fifty four HCC patients, 20 cirrhotic patients and 10 healthy subjects were recruited. Serum levels of GPC3, sulfatase-2 (SULF-2), heparan sulfate proteoglycan (HSPG), insulin-like growth factor-II (IGF-II) were measured by ELISA. In parallel, HCC was induced in 40 male Sprague-Dawley rats in presence/absence of antiGPC-3. Liver impairment was detected by investigating liver sections stained with hematoxylin/eosin and serum ?-fetoprotein (AFP). Liver homogenates of GPC3, SULF-2, and HSPG were measured by ELISA. Gene expression of caspase-3 and IGF-II were assayed by RT-PCR. HCC patients showed significant elevated serum levels of GPC3, IGF-II and SULF-2 accompanied by decreased HSPG. However, treatment of HCC rats with antiGPC-3 significantly reduced serum AFP and showed nearly normal hepatocytes. In addition, antiGPC-3 significantly reduced elevated liver homogenates protein levels of GPC3 and SULF-2 and gene expression of IGF-II and caspase-3. antiGPC-3 restored the reduced hepatic HSPG. antiGPC-3 showed anti-tumor activity as well as hepatoprotective effects. antiGPC-3-chemoprotective effect can be explained by forced reduction of IGF-II expression, restoration of HSPGs, deactivation of SULF-2 and reduction of gene expression of caspase-3. Targeting GPC3 is a promising therapeutic approach for HCC. PMID:25449037

  8. Evaluation of cell proliferation, apoptosis, and dna-repair genes as potential biomarkers for ethanol-induced cns alterations

    PubMed Central

    2012-01-01

    Background Alcohol use disorders (AUDs) lead to alterations in central nervous system (CNS) architecture along with impaired learning and memory. Previous work from our group and that of others suggests that one mechanism underlying these changes is alteration of cell proliferation, apoptosis, and DNA-repair in neural stem cells (NSCs) produced as a consequence of ethanol-induced effects on the expression of genes related to p53-signaling. This study tests the hypothesis that changes in the expression of p53-signaling genes represent biomarkers of ethanol abuse which can be identified in the peripheral blood of rat drinking models and human AUD subjects and posits that specific changes may be correlated with differences in neuropsychological measures and CNS structure. Results Remarkably, microarray analysis of 350 genes related to p53-signaling in peripheral blood leukocytes (PBLs) of binge-drinking rats revealed 190 genes that were significantly altered after correcting for multiple testing. Moreover, 40 of these genes overlapped with those that we had previously observed to be changed in ethanol-exposed mouse NSCs. Expression changes in nine of these genes were tested for independent confirmation by a custom QuantiGene Plex (QGP) assay for a subset of p53-signaling genes, where a consistent trend for decreased expression of mitosis-related genes was observed. One mitosis-related gene (Pttg1) was also changed in human lymphoblasts cultured with ethanol. In PBLs of human AUD subjects seven p53-signaling genes were changed compared with non-drinking controls. Correlation and principal components analysis were then used to identify significant relationships between the expression of these seven genes and a set of medical, demographic, neuropsychological and neuroimaging measures that distinguished AUD and control subjects. Two genes (Ercc1 and Mcm5) showed a highly significant correlation with AUD-induced decreases in the volume of the left parietal supramarginal gyrus and neuropsychological measures. Conclusions These results demonstrate that alcohol-induced changes in genes related to proliferation, apoptosis, and DNA-repair are observable in the peripheral blood and may serve as a useful biomarker for CNS structural damage and functional performance deficits in human AUD subjects. PMID:23095216

  9. Intracellular signaling pathways involved in acetaldehyde-induced collagen and fibronectin gene expression in human hepatic stellate cells

    Microsoft Academic Search

    Gianluca Svegliati-Baroni; Francesco Ridolfi; Antonio Di Sario; Stefania Saccomanno; Emanuele Bendia; Antonio Benedetti; Patricia Greenwel

    2001-01-01

    Ethanol induces liver fibrosis by several means that include, among others, the direct fibrogenic action of acetaldehyde on hepatic stellate cells (HSC). However the mechanisms responsible for this effect are not well understood. In this communication we investigated signal transduction pathways triggered by acetaldehyde leading to upregulation of ?2(I) collagen and fibronectin gene expression in human HSC. Run-on assays showed

  10. Intragastric polyethylene glycol-400 protects against ethanol-induced gastric mucosal lesions despite pretreatment with indomethacin or iodoacetamide

    Microsoft Academic Search

    Candido A. Gutiérrez-Cabano

    1995-01-01

    It has been shown that intragastric administration of polyethylene glycol-400 (PEG-400) by gavage needle protected the rat gastric mucosa from 96% ethanol-induced lesions in a dose-dependent fashion. The inhibitions of the lesions were 10.5, 53.5, 94.6, and 99.2% at doses of 275, 1375, 2750, and 5500 mg\\/kg, respectively. The duration of the protective effect was approximately 12 hr. The gastroprotection

  11. The Ethanol-Induced Stimulation of Rat Duodenal Mucosal Bicarbonate Secretion In Vivo Is Critically Dependent on Luminal Cl–

    PubMed Central

    Sommansson, Anna; Wan Saudi, Wan Salman; Nylander, Olof; Sjöblom, Markus

    2014-01-01

    Alcohol may induce metabolic and functional changes in gastrointestinal epithelial cells, contributing to impaired mucosal barrier function. Duodenal mucosal bicarbonate secretion (DBS) is a primary epithelial defense against gastric acid and also has an important function in maintaining the homeostasis of the juxtamucosal microenvironment. The aim in this study was to investigate the effects of the luminal perfusion of moderate concentrations of ethanol in vivo on epithelial DBS, fluid secretion and paracellular permeability. Under thiobarbiturate anesthesia, a ?30-mm segment of the proximal duodenum with an intact blood supply was perfused in situ in rats. The effects on DBS, duodenal transepithelial net fluid flux and the blood-to-lumen clearance of 51Cr-EDTA were investigated. Perfusing the duodenum with isotonic solutions of 10% or 15% ethanol-by-volume for 30 min increased DBS in a concentration-dependent manner, while the net fluid flux did not change. Pre-treatment with the CFTR inhibitor CFTRinh172 (i.p. or i.v.) did not change the secretory response to ethanol, while removing Cl? from the luminal perfusate abolished the ethanol-induced increase in DBS. The administration of hexamethonium (i.v.) but not capsazepine significantly reduced the basal net fluid flux and the ethanol-induced increase in DBS. Perfusing the duodenum with a combination of 1.0 mM HCl and 15% ethanol induced significantly greater increases in DBS than 15% ethanol or 1.0 mM HCl alone but did not influence fluid flux. Our data demonstrate that ethanol induces increases in DBS through a mechanism that is critically dependent on luminal Cl? and partly dependent on enteric neural pathways involving nicotinic receptors. Ethanol and HCl appears to stimulate DBS via the activation of different bicarbonate transporting mechanisms. PMID:25033198

  12. Quetiapine mitigates the ethanol-induced oxidative stress in brain tissue, but not in the liver, of the rat

    PubMed Central

    Han, Jin-hong; Tian, Hong-zhao; Lian, Yang-yang; Yu, Yi; Lu, Cheng-biao; Li, Xin-min; Zhang, Rui-ling; Xu, Haiyun

    2015-01-01

    Quetiapine, an atypical antipsychotic, has been employed to treat alcoholic patients with comorbid psychopathology. It was shown to scavenge hydroxyl radicals and to protect cultured cells from noxious effects of oxidative stress, a pathophysiological mechanism involved in the toxicity of alcohol. This study compared the redox status of the liver and the brain regions of prefrontal cortex, hippocampus, and cerebellum of rats treated with or without ethanol and quetiapine. Ethanol administration for 1 week induced oxidative stress in the liver and decreased the activity of glutathione peroxidase and total antioxidant capacity (TAC) there. Coadministration of quetiapine did not protect glutathione peroxidase and TAC in the liver against the noxious effect of ethanol, thus was unable to mitigate the ethanol-induced oxidative stress there. The ethanol-induced alteration in the redox status in the prefrontal cortex is mild, whereas the hippocampus and cerebellum are more susceptible to ethanol intoxication. For all the examined brain regions, coadministration of quetiapine exerted effective protection on the antioxidants catalase and total superoxide dismutase and on the TAC, thus completely blocking the ethanol-induced oxidative stress in these brain regions. These protective effects may explain the clinical observations that quetiapine reduced psychiatric symptoms intensity and maintained a good level of tolerability in chronic alcoholism with comorbid psychopathology. PMID:26109862

  13. Effects of L-histidine and histamine H3 receptor modulators on ethanol-induced sedation in mice.

    PubMed

    Didone, Vincent; Quoilin, Caroline; Nyssen, Laura; Closon, Catherine; Tirelli, Ezio; Quertemont, Etienne

    2013-02-01

    Recent studies suggest that the brain histaminergic system and especially the H3 receptors are involved in the regulation of alcohol consumption and alcohol-induced behaviors. Part of this effect might be due to a modulation of ethanol-induced sedation by central histamine. The aim of the present study was to investigate the effects of several histaminergic drugs on ethanol-induced sedation using the loss of righting reflex experimental protocol in female Swiss mice. A pretreatment with L-histidine, the histamine precursor, significantly reduced ethanol-induced sedation, suggesting that brain histamine protects against the sedative effects of ethanol. In a second set of experiments, several H3 receptor agonists (immepip or imetit) and inverse agonists/antagonists (thioperamide, A331440, or BF2.649) were tested. Surprisingly, both H3 receptor agonists and antagonists potentiated the sedative effects of ethanol. This paradoxical effect might be due to the subtle regulatory actions related to the H3 heteroreceptor function. PMID:23089647

  14. PREVENTION OF ETHANOL-INDUCED CHANGES IN REACTIVE OXYGEN PARAMETERS BY aTOCOPHEROL

    Microsoft Academic Search

    STEPHEN C. BONDY; SHIRLEY X. GUO; JAMES D. ADAMS

    Rats were given a 200 mg\\/kg body weight daily dose of a-tocopherol by i.p. injection for 15 days. This resulted in elevated levels of glutathione in both liver and brain, and in a reduced hepatic rate of generation of reactive oxygen species. The depression of hepatic and cerebral glutathione levels in ethanol-consuming rats was prevented by simultaneous treatment with a-tocopherol.

  15. Oxidative stress mediated toxicity exerted by ethanol-inducible CYP2E1

    SciTech Connect

    Wu Defeng [Department of Pharmacology and Biological Chemistry, Box 1603, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029 (United States); Cederbaum, Arthur I. [Department of Pharmacology and Biological Chemistry, Box 1603, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029 (United States)]. E-mail: arthur.cederbaum@mssm.edu

    2005-09-01

    Induction of CYP2E1 by ethanol is one of the central pathways by which ethanol generates a state of oxidative stress in hepatocytes. To study the biochemical and toxicological actions of CYP2E1, our laboratory established HepG2 cell lines which constitutively overexpress CYP2E1 and characterized these cells with respect to ethanol toxicity. Addition of ethanol or an unsaturated fatty acid such as arachidonic acid or iron was toxic to the CYP2E1-expressing cells but not control cells. This toxicity was associated with elevated lipid peroxidation and could be prevented by antioxidants and inhibitors of CYP2E1. Apoptosis occurred in the CYP2E1-expressing cells exposed to ethanol, arachidonic acid, or iron. Removal of GSH caused a loss of viability in the CYP2E1-expressing cells even in the absence of added toxin or pro-oxidant. This was associated with mitochondrial damage and decreased mitochondrial membrane potential. Low concentrations of iron and arachidonic acid synergistically interacted with CYP2E1 to produce cell toxicity, suggesting these nutrients may act as priming or sensitizing agents to alcohol-induced liver injury. Surprisingly, CYP2E1-expressing cells had elevated GSH levels, due to transcriptional activation of glutamate cysteine ligase. Similarly, levels of catalase, alpha-, and microsomal glutathione transferase were also increased, suggesting that upregulation of these antioxidant genes may reflect an adaptive mechanism to remove CYP2E1-derived oxidants. Using co-cultures, interaction between CYP2E1-derived diffusible mediators to activate collagen production in hepatic stellate cells was found. While it is likely that several mechanisms contribute to alcohol-induced liver injury, the linkage between CYP2E1-dependent oxidative stress, mitochondrial injury, stellate cell activation, and GSH homeostasis may contribute to the toxic action of ethanol on the liver. HepG2 cell lines overexpressing CYP2E1 may be a valuable model to characterize the biochemical and toxicological properties of CYP2E1.

  16. Deficiency in AMPK attenuates ethanol-induced cardiac contractile dysfunction through inhibition of autophagosome formation

    PubMed Central

    Guo, Rui; Ren, Jun

    2012-01-01

    Aims Binge drinking often triggers compromised myocardial contractile function while activating AMP-activated protein kinase (AMPK). Given the role of AMPK in the initiation of autophagy through the mammalian target of rapamycin complex 1 (mTORC1) and Unc51-like kinase (ULK1), this study was designed to examine the impact of AMPK deficiency on cardiac function and the mechanism involved with a focus on autophagy following an acute ethanol challenge. Methods and results Wild-type (WT) and transgenic mice overexpressing a kinase-dead (KD) ?2 isoform (K45R mutation) of AMPK were challenged with ethanol. Glucose tolerance, echocardiography, Langendorff heart and cardiomyocyte contractile function, autophagy, and autophagic signalling including AMPK, acetyl-CoA carboxylase (ACC), mTOR, the mTORC1-associated protein Raptor, and ULK1 were examined. Ethanol exposure triggered glucose intolerance and compromised cardiac contraction accompanied by increased phosphorylation of AMPK and ACC as well as autophagosome accumulation (increased LC3II and p62), the effects of which were attenuated or mitigated by AMPK deficiency or inhibition. Ethanol dampened and stimulated, respectively, the phosphorylation of mTOR and Raptor, the effects of which were abolished by AMPK deficiency. ULK1 phosphorylation at Ser757 and Ser777 was down-regulated and up-regulated, respectively, by ethanol, the effect of which was nullified by AMPK deficiency or inhibition. Moreover, the ethanol challenge enhanced LC3 puncta in H9c2 cells and promoted cardiac contractile dysfunction, and these effects were ablated by the inhibition of autophagy or AMPK. Lysosomal inhibition failed to accentuate ethanol-induced increases in LC3II and p62. Conclusion In summary, these data suggest that ethanol exposure may trigger myocardial dysfunction through a mechanism associated with AMPK-mTORC1-ULK1-mediated autophagy. PMID:22451512

  17. Characterization of novel mechanisms for steatosis from global protein hyperacetylation in ethanol-induced mouse hepatocytes.

    PubMed

    Kim, Sun Ju; Kwon, Oh Kwang; Ki, Sung Hwan; Jeong, Tae Cheon; Lee, Sangkyu

    2015-08-01

    Steatosis is the earliest and most common disease of the liver due to chronic ethanol consumption, and stems from alterations in the function of transcription factors related to lipid metabolism. Protein acetylation at the lysine residue (Kac) is known to have diverse functions in cell metabolism. Recent studies showed that ethanol exposure induces global protein hyperacetylation by reducing the deacetylase activities of SIRT1 and SIRT3. Although global acetylome analyses have revealed the involvement of a variety of lysine acetylation sites, the exact sites directly regulated by ethanol exposure are unknown. In this study, to elucidate the exact hyperacetylation sites that contribute to SIRT1 and SIRT3 downregulation, we identified and quantified a total of 1285 Kac sites and 686 Kac proteins in AML-12 cells after ethanol treatment (100 mM) for 3 days. All quantified Kac sites were divided into four quantiles: Q1 (0-15%), Q2 (15-50%), Q3 (50-85%), and Q4 (85-100%). Q4 had 192 Kac sites indicating ethanol-induced hyperacetylation. Using the Motif-x program, the [LXKL], [KH], and [KW] motifs were included in the Q4 category, where [KW] was a specific residue for SIRT3. We also performed gene ontology term and KEGG pathway enrichment analyses. Hyperacetylation sites were significantly enriched in biosynthetic processes and ATPase activities within the biological process and molecular function categories, respectively. In conclusion, ethanol regulates the acetylation of proteins in a variety of metabolic pathways mediated by SIRT1 and SIRT3. As a result, ethanol stimulates increased de novo fatty acid synthesis in hepatocytes. PMID:26056001

  18. Role of defective methylation reactions in ethanol-induced dysregulation of intestinal barrier integrity.

    PubMed

    Thomes, Paul G; Osna, Natalia A; Bligh, Sarah M; Tuma, Dean J; Kharbanda, Kusum K

    2015-07-01

    Alcoholic liver disease (ALD) is a major healthcare challenge worldwide. Emerging evidence reveals that ethanol administration disrupts the intestinal epithelial tight junction (TJ) complex; this defect allows for the paracellular translocation of gut-derived pathogenic molecules to reach the liver to cause inflammation and progressive liver injury. We have previously demonstrated a causative role of impairments in liver transmethylation reactions in the pathogenesis of ALD. We have further shown that treatment with betaine, a methylation agent that normalizes liver methylation potential, can attenuate ethanol-induced liver injury. Herein, we explored whether alterations in methylation reactions play a causative role in disrupting intestinal mucosal barrier function by employing an intestinal epithelial cell line. Monolayers of Caco-2 cells were exposed to ethanol or a-pan methylation reaction inhibitor, tubercidin, in the presence and absence of betaine. The structural and functional integrity of intestinal epithelial barrier was then examined. We observed that exposure to either ethanol or tubercidin disrupted TJ integrity and function by decreasing the localization of TJ protein occludin-1 to the intracellular junctions, reducing transepithelial electrical resistance and increasing dextran influx. All these detrimental effects of ethanol and tubercidin were attenuated by co-treatment with betaine. We further show that the mechanism of betaine protection was through BHMT-mediated catalysis. Collectively, our data suggest a novel mechanism for alcohol-induced gut leakiness and identifies the importance of normal methylation reactions in maintaining TJ integrity. We also propose betaine as a potential therapeutic option for leaky gut in alcohol-consuming patients who are at the risk of developing ALD. PMID:25931143

  19. Pdgfra protects against ethanol-induced craniofacial defects in a zebrafish model of FASD

    PubMed Central

    McCarthy, Neil; Wetherill, Leah; Lovely, C. Ben; Swartz, Mary E.; Foroud, Tatiana M.; Eberhart, Johann K.

    2013-01-01

    Human birth defects are highly variable and this phenotypic variability can be influenced by both the environment and genetics. However, the synergistic interactions between these two variables are not well understood. Fetal alcohol spectrum disorders (FASD) is the umbrella term used to describe the wide range of deleterious outcomes following prenatal alcohol exposure. Although FASD are caused by prenatal ethanol exposure, FASD are thought to be genetically modulated, although the genes regulating sensitivity to ethanol teratogenesis are largely unknown. To identify potential ethanol-sensitive genes, we tested five known craniofacial mutants for ethanol sensitivity: cyp26b1, gata3, pdgfra, smad5 and smoothened. We found that only platelet-derived growth factor receptor alpha (pdgfra) interacted with ethanol during zebrafish craniofacial development. Analysis of the PDGF family in a human FASD genome-wide dataset links PDGFRA to craniofacial phenotypes in FASD, prompting a mechanistic understanding of this interaction. In zebrafish, untreated pdgfra mutants have cleft palate due to defective neural crest cell migration, whereas pdgfra heterozygotes develop normally. Ethanol-exposed pdgfra mutants have profound craniofacial defects that include the loss of the palatal skeleton and hypoplasia of the pharyngeal skeleton. Furthermore, ethanol treatment revealed latent haploinsufficiency, causing palatal defects in ?62% of pdgfra heterozygotes. Neural crest apoptosis partially underlies these ethanol-induced defects in pdgfra mutants, demonstrating a protective role for Pdgfra. This protective role is mediated by the PI3K/mTOR pathway. Collectively, our results suggest a model where combined genetic and environmental inhibition of PI3K/mTOR signaling leads to variability within FASD. PMID:23861062

  20. Ganoderma Lucidum Pharmacopuncture for Teating Ethanol-induced Chronic Gastric Ulcers in Rats

    PubMed Central

    Park, Jae-Heung; Jang, Kyung-Jun; Kim, Cheol-Hong; Kim, Jung-Hee; Kim, Young-Kyun; Yoon, Hyun-Min

    2015-01-01

    Objectives: The stomach is a sensitive digestive organ that is susceptible to exogenous pathogens from the diet. In response to such pathogens, the stomach induces oxidative stress, which might be related to the development of both gastric organic disorders such as gastritis, gastric ulcers, and gastric cancer, and functional disorders such as functional dyspepsia. This study was accomplished to investigate the effect of Ganoderma lucidum pharmacopuncture (GLP) on chronic gastric ulcers in rats. Methods: The rats were divided into 4 groups of 8 animals each: the normal, the control, the normal saline (NP) and the GLP groups. In this study, the modified ethanol gastritis model was used. The rats were administrated 56% ethanol orally every other day. The dose of ethanol was 8 g/kg body weight. The normal group received the same amount of normal saline instead of ethanol. The NP and the GLP groups were treated with injection of saline and GLP respectively. The control group received no treatment. Two local acupoints CV12 (??) and ST36 (???) were used. All laboratory rats underwent treatment for 15 days. On last day, the rats were sacrificed and their stomachs were immediately excised. Results: Ulcers of the gastric mucosa appeared as elongated bands of hemorrhagic lesions parallel to the long axis of the stomach. In the NP and GLP groups, the injuries to the gastric mucosal injuries were not as severe as they were in the control group. Wound healings of the chronic gastric ulcers was promoted by using GLP and significant alterations of the indices in the gastric mucosa were observed. Such protection was demonstrated by gross appearance, histology and immunehistochemistry staining for Bcl-2-associated X (BAX), B-cell lymphoma 2 (Bcl-2) and Transforming growth factor-beta 1 (TGF-?1). Conclusion: These results suggest that GLP at CV12 and ST36 can provide significant protection to the gastric mucosa against an ethanol induced chronic gastric ulcer. PMID:25830061

  1. Inhibitory effect on proliferation of vascular smooth muscle cells and protective effect on CCl(4)-induced hepatic damage of HEAI extract.

    PubMed

    Choi, Won-Sik; Kim, Chang-Jin; Park, Byeoung-Soo; Lee, Sung-Eun; Takeoka, Gary R; Kim, Dong-Goo; Lanpiao, Xiang; Kim, Jeong-Han

    2005-08-22

    The effects of methanol extract from Hericium erinaceus cultivated with Artemisia iwayomogi (HEAI) on proliferation of vascular smooth muscle cells and CCl(4)-induced hepatic damage were evaluated. HEAI was shown to have a potent inhibitory effect on the proliferation of vascular smooth muscle cells (VSMCs). Interestingly, a methanol extract of Hericium erinaceus showed no inhibitory effect on the proliferation of VSMCs, while a methanol extract of Artemisia iwayomogi possessed strong inhibitory effects on the proliferation of VSMCs. Therefore, the inhibitory effects of HEAI may be caused by the changes of chemical components in the culture broth after the addition of Artemisia iwayomogi in the HEAI growth media. HEAI also had a strong protective effect on CCl(4)-induced hepatic damage in rats. The activity was evaluated using biochemical parameters such as glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and alkaline phosphatase (ALP). HEAI treatment caused a significant reduction in the activity of GOT but not of GPT and ALP in comparison with CCl(4) treatment alone. Histopathological studies showed that liver samples treated with HEAI were significantly different when compared to non-treated animals after CCl(4) exposure. PMID:15941638

  2. Ethanol-Induced Microphthalmia is Not Mediated by Changes in Retinoic Acid or Sonic Hedgehog Signaling During Retinal Neurogenesis

    PubMed Central

    Kashyap, Bhavani; Frey, Ruth A.; Stenkamp, Deborah L.

    2012-01-01

    Background Microphthalmia (reduced eye size), generally accompanied by vision defects, is a hallmark of fetal alcohol spectrum disorder (FASD) in humans. In zebrafish, embryonic ethanol exposure over the time of retinal neurogenesis also results in microphthalmia. This microphthalmia is in part the consequence of reduced retinal cell differentiation, including photoreceptors. Here we pursue 2 signaling pathways implicated in other aspects of FASD pathogenesis: retinoic acid (RA) and Sonic hedgehog (Shh). Methods We evaluated markers for RA and Shh signaling within the eyes of embryos treated with ethanol during the period of retinal neurogenesis. We also perrormed rescue experiments using administration of exogenous RA and microinjection of cholesterol, which augments Shh signaling. Results Using sequential or co-treatments, RA did not rescue ethanol-induced microphthalmia at any concentration tested. In addition, RA itself caused microphthalmia, although the underlying mechanisms were distinct from those or ethanol. Interestingly, RA treatment appeared to recover photoreceptor differentiation in a concentration-dependent manner. This may be an independent effect or exogenous RA, as ethanol treatment alone did not alter RA signaling in the eye. Cholesterol injection also did not rescue ethanol-induced microphthalmia at any concentration tested, and ethanol treatments did not alter expression of shh, or of ptc-2, which is normally regulated by Shh signaling. Conclusions Together these findings indicate that, during the time of retinal neurogenesis, effects of ethanol on eye development are likely independent of the RA and Shh signaling pathways. These studies suggest that FASD intervention strategies based upon augmentation or RA or Shh signaling may not prevent ethanol-induced microphthalmia. PMID:21554333

  3. Protective effect of 1,25-dihydroxyvitamin D3 on ethanol-induced intestinal barrier injury both in vitro and in vivo.

    PubMed

    Chen, Shan-Wen; Ma, Yuan-Yuan; Zhu, Jing; Zuo, Shuai; Zhang, Jun-Ling; Chen, Zi-Yi; Chen, Guo-Wei; Wang, Xin; Pan, Yi-Sheng; Liu, Yu-Cun; Wang, Peng-Yuan

    2015-09-01

    Studies have suggested the role of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in protecting intestinal barrier function from injuries induced by multiple reagents. Vitamin D deficiency was reported to be associated with poor prognosis in patients with alcoholic liver disease (ALD). This study is designed to investigate the effect of 1,25(OH)2D3 on ethanol-induced intestinal barrier dysfunction and the underlying mechanisms utilizing Caco-2 cell monolayers and a mouse model with acute ethanol injury. In Caco-2 monolayers, ethanol significantly increased monolayer permeability, disrupted TJ distribution, increased phosphorylation level of MLC, and induced generation of ROS compared with controls. However, pre-treatment with 1,25(OH)2D3 greatly ameliorated the ethanol-induced barrier dysfunction, TJ disruption, phosphorylation level of MLC, and generation of ROS compared with ethanol-exposed monolayers. Mice fed with vitamin d-sufficient diet had a higher plasma level of 25(OH)D3 and were more resistant to ethanol-induced acute intestinal barrier injury compared with the vitamin d-deficient group. These results suggest that the suppression of generation of ROS and increased phosphorylation level of MLC might be one of the mechanisms underlying the protective effect of 1,25(OH)2D3 on ethanol-induced intestinal barrier injury and provide evidence for the application of vitamin D as therapeutic factors against ethanol-induced gut leakiness. PMID:26068064

  4. Ethanol-induced apoptosis in human liver adenocarcinoma cells (SK-Hep1): Fas- and mitochondria-mediated pathways and interaction with MAPK signaling system.

    PubMed

    Morio, Yuri; Tsuji, Mayumi; Inagaki, Manami; Nakagawa, Mai; Asaka, Yuri; Oyamada, Hideto; Furuya, Kanji; Oguchi, Katsuji

    2013-09-01

    For studying molecular mechanisms regulating the fate of ethanol-treated hepatocytes, involvement of Fas in ethanol-induced apoptosis was examined in human liver adenocarcinoma (SK-Hep1) cells in which the function of Fas-associated death domain (FADD) protein was knocked down by transfection. In FADD-knocked down cells, while ethanol-induced increase in generation of reactive oxygen species (ROS) was unaffected, apoptosis was significantly suppressed, demonstrating the involvement of Fas in ethanol-induced hepatocyte apoptosis more directly than in the past reports. On the other hand, effects of mitogen-activated protein kinase (MAPK), which is well known to determine the fate of various cells, on ethanol-induced apoptosis have not been examined in SK-Hep1 cells. Of three major MAPKs, only p38 MAPK and JNK were found activated by 200 mM ethanol treatment. When cells were incubated with inhibitors of p38 MAPK and JNK, ethanol-induced apoptosis was decreased while ROS generation was unaffected, and examination of pro-apoptotic Bax and anti-apoptotic Bcl-2 levels showed decrease of the former and increase of the latter. We concluded that oxidative stress inflicted by ROS triggered Fas-mediated and mitochondria-mediated apoptotic pathways in ethanol-treated SK-Hep1 cells, and that p38 MAPK and JNK were promoting mitochondrial pathway, suggesting interaction between apoptosis and MAPK signaling systems. PMID:23726865

  5. The parallel universe: microRNAs and their role in chronic hepatitis, liver tissue damage and hepatocarcinogenesis.

    PubMed

    Haybaeck, Johannes; Zeller, Nicolas; Heikenwalder, Mathias

    2011-01-01

    In recent years, enormous progress has been made in identifying microRNAs (miRNAs) as important regulators of gene expression and their association with or control of various liver diseases such as fibrosis, hepatitis and hepatocellular carcinoma (HCC). Indeed, many genes encoding miRNAs as well as their targets have been described and their direct or indirect link to the respective liver diseases has been investigated in various experimental systems as well as in human tissue. Here we discuss current knowledge of miRNAs and their involvement in liver diseases, elaborating in particular on the contribution of miRNAs to hepatitis, fibrosis and HCC formation. We also debate possible prognostic, predictive and therapeutic values of respective miRNAs in liver diseases. The discovery of liver disease related miRNAs has constituted a major breakthrough in liver research and will most likely be of high relevance for future therapeutic strategies, especially when dealing with hepatitis, fibrosis and HCC. PMID:22020555

  6. Viral Hepatitis D

    Microsoft Academic Search

    John M. Taylor

    \\u000a Viral hepatitis D, also known as hepatitis delta virus (HDV), was first discovered by Mario Rizzetto in 1977, in a study of\\u000a Italian patients infected with hepatitis B virus (HBV), who seemed to have a more damaging liver disease. For more information\\u000a on HBV, please see Chap. 37. In liver biopsies from such patients, a serum antibody detected a novel

  7. Ecklonia cava Polyphenol Has a Protective Effect against Ethanol-Induced Liver Injury in a Cyclic AMP-Dependent Manner

    PubMed Central

    Yamashita, Haruka; Goto, Mayu; Matsui-Yuasa, Isao; Kojima-Yuasa, Akiko

    2015-01-01

    Previously, we showed that Ecklonia cava polyphenol (ECP) treatment suppressed ethanol-induced increases in hepatocyte death by scavenging intracellular reactive oxygen species (ROS) and maintaining intracellular glutathione levels. Here, we examined the effects of ECP on the activities of alcohol-metabolizing enzymes and their regulating mechanisms in ethanol-treated hepatocytes. Isolated hepatocytes were incubated with or without 100 mM ethanol. ECP was dissolved in dimethylsulfoxide. ECP was added to cultured cells that had been incubated with or without ethanol. The cells were incubated for 0–24 h. In cultured hepatocytes, the ECP treatment with ethanol inhibited cytochrome P450 2E1 (CYP2E1) expression and activity, which is related to the production of ROS when large quantities of ethanol are oxidized. On the other hand, ECP treatment with ethanol increased the activity of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase. These changes in activities of CYP2E1 and ADH were suppressed by treatment with H89, an inhibitor of protein kinase A. ECP treatment with ethanol enhanced cyclic AMP concentrations compared with those of control cells. ECP may be a candidate for preventing ethanol-induced liver injury via regulating alcohol metabolic enzymes in a cyclic AMP-dependent manner. PMID:26096275

  8. [Ethanol-induced influence on the structure and arsenate adsorption of resin-based nano-hydrated ferric oxide].

    PubMed

    Wan, Qi; Li, Xu-Chun; Pan, Bing-Cai

    2013-08-01

    Here the role of ethanol in the synthesis of a new nanocomposite (D201-HFO) was evaluated in terms of its structure variation and arsenate adsorption. Results indicated that the ethanol-induced procedure improved the dispersion of HFO inside the polymer host D201 and increased the HFO sorption capacities towards arsenate by 20%. Also, the ethanol-induced procedure resulted in the increase of pore size, pore volume, and specific surface area of D201-HFO by 52%, 65% and 28%, respectively. Nevertheless, ethanol rinsing did not affect the mechanical strength of D201-HFO and the crystal type of the immobilized HFO. Little effects of the ethanol process was observed on the pH and co-anion dependent adsorption of arsenate. Furthermore, the ethanol step posed insignificant influence on the fix-bed adsorption and the repeated use of the adsorbent. The results showed that the ethanol procedure exerted little influence on the sorption properties of D201-HFO from the viewpoint of practical application and thus, it could not be included. PMID:24191562

  9. Hepatitis C virus (HCV) genotype, tissue HCV antigens, hepatocellular expression of HLA-A,B,C, and intercellular adhesion-1 molecules. Clues to pathogenesis of hepatocellular damage and response to interferon treatment in patients with chronic hepatitis C.

    PubMed Central

    Ballardini, G; Groff, P; Pontisso, P; Giostra, F; Francesconi, R; Lenzi, M; Zauli, D; Alberti, A; Bianchi, F B

    1995-01-01

    To obtain information on the mechanisms of hepatocellular damage and the determinants of response to interferon, hepatitis C virus (HCV) genotype, tissue HCV antigens, hepatocellular expression of HLA-A,B,C and intercellular adhesion-1 molecules, and the number of lobular T lymphocytes were studied in 38 anti-HCV-positive patients. 14 patients did not show a primary response to interferon treatment. HCV genotype 1b was detected in 11 of them. They displayed higher scores of HCV-positive hepatocytes, HLA-A,B,C, and ICAM-1 molecules expression than with the responders. HCV-infected hepatocytes maintained the capacity to express HLA-A,B,C and ICAM-1 molecules. CD8-positive T cells in contact with infected hepatocytes and Councilman-like bodies were observed. A significant correlation was found between the number of lobular CD8-positive T cells and alanine amino transferase levels. No differences were observed in clinical, biochemical, and histological features between patients with high and low number of hepatocytes containing HCV antigens. These data suggest a prominent role of T cell-mediated cytotoxicity in the genesis of hepatocellular damage. The high expression of interferon-inducible antigens like HLA-A,B,C molecules suggests the presence of strong activation of the interferon system possibly related to high HCV replication in nonresponder patients infected with genotype 1b. Images PMID:7738174

  10. Peroxisome proliferators-activated alpha agonist treatment ameliorates hepatic damage in rats with obstructive jaundice: an experimental study

    Microsoft Academic Search

    Mehmet Cindoruk; Mustafa Kerem; Tarkan Karakan; Bulent Salman; Okan Akin; Murat Alper; Ozlem Erdem; Selahattin Ünal

    2007-01-01

    BACKGROUND: Peroxisome proliferators-activated receptor alpha (PPAR?) activation modulates cholesterol metabolism and suppresses bile acid synthesis. This study aims to evaluate the effect of short-term administration of fenofibrate, a PPAR? agonist, on proinflammatory cytokines, apoptosis, and hepatocellular damage in cholestasis. METHODS: Forty male Wistar rats were randomly divided into four groups: I = sham operated, II = bile duct ligation (BDL),

  11. A Systems-Based Computational Model for Dose-Response Comparisons of Two Mode of Action Hypotheses for Ethanol-Induced Neurodevelopmental Toxicity

    Microsoft Academic Search

    J. M. Gohlke; W. C. Griffith; E. M. Faustman

    2005-01-01

    Investigations into the potential mechanisms for ethanol- induced developmental toxicity have been ongoing for over 30 years since Fetal Alcohol Syndrome (FAS) was first described. Neurodevelopmental endpoints are particularly sensitive to in utero exposure to alcohol as suggested by the more prevalent alcohol-related neurodevelopmental disorder (ARND). The in- hibition of proliferation during neurogenesis and the induction of apoptosis during the

  12. AMELIORATION OF ETHANOL-INDUCED DYSMORPHOGENESIS BY ADENOVIRAL-MEDIATED CU,ZN-SOD AND MN-SOD EXPRESSION IN NEURULATION STAGED MOUSE EMBRYOS IN VITRO

    EPA Science Inventory

    AMELIORATION OF ETHANOL-INDUCED DYSMORPHOGENESIS BY ADENOVIRAL-MEDIATED Cu,Zn-SOD AND Mn-SOD EXPRESSION IN NEURULATION STAGED MOUSE EMBRYOS IN VITRO. JB Smith1, PC Hartig3, MR Blanton3, KK Sulik1,2, and ES Hunter3. 1Department of Cell and Developmental Biology and 2Bowles Cente...

  13. Ethanol induces cell-cycle activity and reduces stem cell diversity to alter both regenerative capacity and differentiation potential of cerebral cortical neuroepithelial precursors

    Microsoft Academic Search

    Daniel R Santillano; Leena S Kumar; Terasa L Prock; Cynthia Camarillo; Joseph D Tingling; Rajesh C Miranda

    2005-01-01

    BACKGROUND: The fetal cortical neuroepithelium is a mosaic of distinct progenitor populations that elaborate diverse cellular fates. Ethanol induces apoptosis and interferes with the survival of differentiating neurons. However, we know little about ethanol's effects on neuronal progenitors. We therefore exposed neurosphere cultures from fetal rat cerebral cortex, to varying ethanol concentrations, to examine the impact of ethanol on stem

  14. Suppression of Ethanol-Reinforced Behavior by Naltrexone Is Associated with Attenuation of the Ethanol-Induced Increase in Dialysate Dopamine Levels in the Nucleus Accumbens

    Microsoft Academic Search

    Rueben A. Gonzales; Friedbert Weiss

    The opiate antagonist naltrexone suppresses ethanol- reinforced behavior in animals and decreases ethanol intake in humans. However, the mechanisms underlying these actions are not well understood. Experiments were designed to test the hypothesis that naltrexone attenuates the rewarding properties of ethanol by interfering with ethanol-induced stimulation of dopamine activity in the nucleus accumbens (NAcc). Simulta- neous measures of the effects

  15. Pyranocycloartobiloxanthone A, a novel gastroprotective compound from Artocarpus obtusus Jarret, against ethanol-induced acute gastric ulcer in vivo.

    PubMed

    Sidahmed, Heyam M A; Hashim, Najihah Mohd; Amir, Junaidah; Abdulla, Mahmood Ameen; Hadi, A Hamid A; Abdelwahab, Siddig Ibrahim; Taha, Manal Mohamed Elhassan; Hassandarvish, Pouya; Teh, Xinsheng; Loke, Mun Fai; Vadivelu, Jamuna; Rahmani, Mawardi; Mohan, Syam

    2013-07-15

    Pyranocycloartobiloxanthone A (PA), a xanthone derived from the Artocarpus obtusus Jarret, belongs to the Moraceae family which is native to the tropical forest of Malaysia. In this study, the efficacy of PA as a gastroprotective compound was examined against ethanol-induced ulcer model in rats. The rats were pretreated with PA and subsequently exposed to acute gastric lesions induced by absolute ethanol. The ulcer index, gastric juice acidity, mucus content, histological analysis, glutathione (GSH) levels, malondialdehyde level (MDA), nitric oxide (NO) and non-protein sulfhydryl group (NP-SH) contents were evaluated in vivo. The activities of PA as anti-Helicobacter pylori, cyclooxygenase-2 (COX-2) inhibitor and free radical scavenger were also investigated in vitro. The results showed that the oral administration of PA protects gastric mucosa from ethanol-induced gastric lesions. PA pretreatment significantly (p<0.05) restored the depleted GSH, NP-SH and NO levels in the gastric homogenate. Moreover, PA significantly (p<0.05) reduced the elevated MDA level due to ethanol administration. The gastroprotective effect of PA was associated with an over expression of HSP70 and suppression of Bax proteins in the ulcerated tissue. In addition, PA exhibited a potent FRAP value and significant COX-2 inhibition. It also showed a significant minimum inhibitory concentration (MIC) against H. pylori bacterium. The efficacy of PA was accomplished safely without the presence of any toxicological parameters. The results of the present study indicate that the gastroprotective effect of PA might contribute to the antioxidant and anti-inflammatory properties as well as the anti-apoptotic mechanism and antibacterial action against Helicobacter pylori. PMID:23570997

  16. Preventive effect of polysaccharides from the large yellow croaker swim bladder on HCl/ethanol induced gastric injury in mice.

    PubMed

    Chen, Shaocheng; Zhu, Kai; Wang, Rui; Zhao, Xin

    2014-07-01

    In the present study the preventive effect of polysaccharides from the large yellow croaker swim bladder (PLYCSB) on HCl/ethanol-induced gastric injury in ICR mice was investigated. A high dose of PLYCSB (50 mg/kg) was found to reduce the levels of the serum proinflammatory cytokines interleukin (IL)-1?, IL-6, IL-8, as well as increase the levels of IL-4 compared with those in mice treated with a low dose of PLYCSB (25 mg/kg) and control mice. The somatostatin and vasoactive intestinal peptide serum levels in PLYCSB-treated mice were higher compared with those in control mice, whilst motilin and substance P serum levels were lower compared with those in control mice. The extent of the gastric injury in the mice treated with PLYCSB was lower compared with that in the control mice; however, the results obtained for mice treated with a high dose of PLYCSB were similar to those for omeprazole-treated mice. In addition, the superoxide dismutase and glutathione peroxidase activities of PLYCSB-treated mice were higher compared with those of the control mice, and similar to those observed in normal and omeprazole-treated mice. Furthermore, PLYCSB-treated mice showed levels of nitric oxide and malondialdehyde that were similar to those in the normal group. Using PCR and western blot analysis, it was demonstrated that PLYCSB significantly inhibited inflammation in the tissues of the HCl/ethanol induced gastric injury mice by downregulating the expression of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-? and IL-1?. These results suggest that PLYCSB has an inhibitory effect against gastric injury that is comparable to that of the gastric injury drug omeprazole. Therefore, PLYCSB has the potential to be used as a natural therapeutic drug. PMID:24944640

  17. Preventive effect of polysaccharides from the large yellow croaker swim bladder on HCl/ethanol induced gastric injury in mice

    PubMed Central

    CHEN, SHAOCHENG; ZHU, KAI; WANG, RUI; ZHAO, XIN

    2014-01-01

    In the present study the preventive effect of polysaccharides from the large yellow croaker swim bladder (PLYCSB) on HCl/ethanol-induced gastric injury in ICR mice was investigated. A high dose of PLYCSB (50 mg/kg) was found to reduce the levels of the serum proinflammatory cytokines interleukin (IL)-1?, IL-6, IL-8, as well as increase the levels of IL-4 compared with those in mice treated with a low dose of PLYCSB (25 mg/kg) and control mice. The somatostatin and vasoactive intestinal peptide serum levels in PLYCSB-treated mice were higher compared with those in control mice, whilst motilin and substance P serum levels were lower compared with those in control mice. The extent of the gastric injury in the mice treated with PLYCSB was lower compared with that in the control mice; however, the results obtained for mice treated with a high dose of PLYCSB were similar to those for omeprazole-treated mice. In addition, the superoxide dismutase and glutathione peroxidase activities of PLYCSB-treated mice were higher compared with those of the control mice, and similar to those observed in normal and omeprazole-treated mice. Furthermore, PLYCSB-treated mice showed levels of nitric oxide and malondialdehyde that were similar to those in the normal group. Using PCR and western blot analysis, it was demonstrated that PLYCSB significantly inhibited inflammation in the tissues of the HCl/ethanol induced gastric injury mice by downregulating the expression of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-? and IL-1?. These results suggest that PLYCSB has an inhibitory effect against gastric injury that is comparable to that of the gastric injury drug omeprazole. Therefore, PLYCSB has the potential to be used as a natural therapeutic drug. PMID:24944640

  18. Protective Effect of Daidzein against Acute Ethanol-induced Lipid Peroxidation in Rat Jejunum

    Microsoft Academic Search

    KANAKO NAKAGAWA; JUNKO ADACHI; MAX C. Y. WONG; YASUHIRO UENO

    Ethanol causes extensive damage to the intestinal tract from the oropharynx to the rectum. The jejunum has also been shown to be particularly vulnerable to the deleterious effects of ethanol. We hypothesized that (I) the pathogenesis of acute alcohol-mediated injury in the small intestine involves generation of reactive oxygen species, and consequentially, enhanced lipid peroxidation; (II) the pathogenic changes due

  19. Hepatic Protection by Noni Fruit Juice Against CCl 4 Induced Chronic Liver Damage in Female SD Rats

    Microsoft Academic Search

    Mian-Ying Wang; Gary Anderson; Diane Nowicki; Jarakae Jensen

    2008-01-01

    Morinda citrifolia L. (noni) has been used throughout the Pacific, Southeast Asia, Central America, and the Caribbean for a variety of health\\u000a conditions, including heart and liver ailments. In this study, we examined the hepatoprotective effects of TAHITIAN NONI®\\u000a Juice (TNJ) against CCl4-induced chronic liver damage in female Sprague Dawley (SD) rats. Twelve female SD rats were divided into control,

  20. Lipid peroxidation and hepatic antioxidants in alcoholic liver disease.

    PubMed Central

    Situnayake, R D; Crump, B J; Thurnham, D I; Davies, J A; Gearty, J; Davis, M

    1990-01-01

    The generation of hepatic liver peroxidation by free radicals has been proposed as a mechanism for ethanol induced hepatotoxicity. To investigate this hypothesis, lipid extracts from hepatic needle biopsy specimens from alcoholic subjects were examined for evidence of lipid peroxidation by measuring total conjugated dienes by derivative spectroscopy and, after hydrolysis of hepatic lipid extract and reverse phase high performance liquid chromatography, the molar ratio between a diene-conjugated linoleic acid isomer (18:2 (9,11)) and the parent linoleic acid isomer (18:2(9,12)). Changes were related to hepatic histology, iron deposition, glutathione and vitamin E values. Derivative spectroscopy minima suggestive of diene conjugation were identified at 233 and 242 nm and correlated weakly, suggesting these two minima may represent different classes of lipid dienes. There was a weak relation with inflammatory histological changes in the biopsy specimen but no correlation with hepatic iron grade, glutathione, or vitamin E lipid ratio. The proportion of 18:2(9,11) linoleic acid in hepatic lipids correlated significantly with inflammatory histological features and inversely with hepatic glutathione. Furthermore, hepatic glutathione was lower in biopsy specimens with greater iron staining. The ratio of vitamin E to lipid was not related to histological group, inflammation, or iron grade. These findings suggest that excess alcohol consumption leads to hepatic inflammation and lipid peroxidation. PMID:2253918

  1. Hepatoprotective Activity of Methanolic Extract of Bauhinia purpurea Leaves against Paracetamol-Induced Hepatic Damage in Rats

    PubMed Central

    Yahya, F.; Mamat, S. S.; Kamarolzaman, M. F. F.; Seyedan, A. A.; Jakius, K. F.; Mahmood, N. D.; Shahril, M. S.; Suhaili, Z.; Mohtarrudin, N.; Susanti, D.; Somchit, M. N.; Teh, L. K.; Salleh, M. Z.; Zakaria, Z. A.

    2013-01-01

    In an attempt to further establish the pharmacological properties of Bauhinia purpurea (Fabaceae), hepatoprotective potential of methanol extract of B. purpurea leaves (MEBP) was investigated using the paracetamol- (PCM-) induced liver toxicity in rats. Five groups of rats (n = 6) were used and administered orally once daily with 10% DMSO (negative control), 200?mg/kg silymarin (positive control), or MEBP (50, 250, and 500?mg/kg) for 7 days, followed by the hepatotoxicity induction using paracetamol (PCM). The blood samples and livers were collected and subjected to biochemical and microscopical analysis. The extract was also subjected to antioxidant study using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay with the total phenolic content (TPC) also determined. From the histological observation, lymphocyte infiltration and marked necrosis were observed in PCM-treated groups (negative control), whereas maintenance of the normal hepatic structural was observed in group pretreated with silymarin and MEBP. Hepatotoxic rats pretreated with silymarin or MEBP exhibited significant decrease (P < 0.05) in ALT and AST enzyme level. Moreover, the extract also exhibited antioxidant activity and contained high TPC. In conclusion, MEBP exerts potential hepatoprotective activity that could be partly attributed to its antioxidant activity and high phenolic content and thus warrants further investigation. PMID:23853662

  2. Hepatoprotective Activity of Methanolic Extract of Bauhinia purpurea Leaves against Paracetamol-Induced Hepatic Damage in Rats.

    PubMed

    Yahya, F; Mamat, S S; Kamarolzaman, M F F; Seyedan, A A; Jakius, K F; Mahmood, N D; Shahril, M S; Suhaili, Z; Mohtarrudin, N; Susanti, D; Somchit, M N; Teh, L K; Salleh, M Z; Zakaria, Z A

    2013-01-01

    In an attempt to further establish the pharmacological properties of Bauhinia purpurea (Fabaceae), hepatoprotective potential of methanol extract of B. purpurea leaves (MEBP) was investigated using the paracetamol- (PCM-) induced liver toxicity in rats. Five groups of rats (n = 6) were used and administered orally once daily with 10% DMSO (negative control), 200?mg/kg silymarin (positive control), or MEBP (50, 250, and 500?mg/kg) for 7 days, followed by the hepatotoxicity induction using paracetamol (PCM). The blood samples and livers were collected and subjected to biochemical and microscopical analysis. The extract was also subjected to antioxidant study using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay with the total phenolic content (TPC) also determined. From the histological observation, lymphocyte infiltration and marked necrosis were observed in PCM-treated groups (negative control), whereas maintenance of the normal hepatic structural was observed in group pretreated with silymarin and MEBP. Hepatotoxic rats pretreated with silymarin or MEBP exhibited significant decrease (P < 0.05) in ALT and AST enzyme level. Moreover, the extract also exhibited antioxidant activity and contained high TPC. In conclusion, MEBP exerts potential hepatoprotective activity that could be partly attributed to its antioxidant activity and high phenolic content and thus warrants further investigation. PMID:23853662

  3. [Pharmacological correction of immuno-metabolic disorders with the peptide Gly-His-Lys in hepatic damage induced by tetrachloromethane].

    PubMed

    Smakhtin, M Iu; Konoplia, A I; Sever'ianova, L A; Shve?nov, I A

    2003-01-01

    10-day intraperitoneal administration of the tripeptie Gly-His-Lys in doses 2.5 and 150 mu/kg raises of mitotic index of hepatocytes in acute toxic damage to the liver. In the dose 1.5 mu/kg this peptie corrects both functional activity of hepatocytes and immunological responsiveness. In a dose of 150 mu/kg the peptie has a more potent immunosuppressive action and deteriorates biochemical indices of blood serum as well as dystrophic changes in the liver. PMID:12838768

  4. 1H and 31P NMR Lipidome of Ethanol-Induced Fatty Liver

    PubMed Central

    Fernando, Harshica; Kondraganti, Shakuntala; Bhopale, Kamlesh K.; Volk, David E.; Neerathilingam, Muniasamy; Kaphalia, Bhupendra S.; Luxon, Bruce A.; Boor, Paul J.; Ansari, G. A. Shakeel

    2011-01-01

    Background Hepatic steatosis (fatty liver), an early and reversible stage of alcoholic liver disease, is characterized by triglyceride deposition in hepatocytes, that can advance to steatohepatitis, fibrosis, cirrhosis, and ultimately to hepatocellular carcinoma. In the present work, we studied altered plasma and hepatic lipid metabolome (lipidome) to understand the mechanisms and lipid pattern of early stage alcohol induced-fatty liver. Methods Male Fischer 344 rats were fed 5% alcohol in a Lieber-DeCarli diet. Control rats were pair-fed an equivalent amount of maltose-dextrin. After one month, animals were sacrificed and plasma collected. Livers were excised for morphological, immunohistochemical, and biochemical studies. The lipids from plasma and livers were extracted with methyl-tert-butyl ether and analyzed by 750/800 MHz proton nuclear magnetic resonance (1H NMR) and phosphorus (31P) NMR spectroscopy on a 600 MHz spectrometer. The NMR data were then subjected to multivariate statistical analysis. Results Hemotoxylin & Eosin and Oil Red O stained liver sections showed significant fatty infiltration. Immunohistochemical analysis of liver sections from ethanol-fed rats showed no inflammation (absence of CD3 positive cells) or oxidative stress (absence of malondialdehyde reactivity or 4-hydroxynonenal positive straining). Cluster analysis and principal component analysis of 1H NMR data of lipid extracts of both plasma and livers showed a significant difference in the lipid metabolome of ethanol-fed vs. control rats. 31P NMR data of liver lipid extracts showed significant changes in phospholipids similar to 1H NMR data. 1H NMR data of plasma and liver reflected several changes while comparison of 1H NMR and 31P NMR data offered a correlation among the phospholipids. Conclusions Our results show that alcohol consumption alters metabolism of cholesterol, triglycerides and phospholipids that could contribute to the development of fatty liver. These studies also indicate that fatty liver precedes oxidative stress and inflammation. The similarities observed in plasma and liver lipid profiles offer a potential methodology for detecting early stage alcohol-induced fatty liver disease by analyzing the plasma lipid profile. PMID:20682011

  5. Association of Iron Overload with Oxidative Stress, Hepatic Damage and Dyslipidemia in Transfusion-Dependent ?-Thalassemia/HbE Patients.

    PubMed

    Sengsuk, Chintana; Tangvarasittichai, Orathai; Chantanaskulwong, Prasert; Pimanprom, Ampai; Wantaneeyawong, Somsak; Choowet, Anuchit; Tangvarasittichai, Surapon

    2014-07-01

    Blood transfusion can be a life-saving therapy for ?-thalassemia major and ?-thalassemia/HbE (?-TM) patients with chronic anemia, major caused severe iron overload particularly in ?-TM patients received only blood transfusion therapy. We aim to evaluate the association of iron overload with oxidative stress, liver damage, and elevated very low density lipoprotein cholesterol (VLDL-C) in transfusion-dependent ?-TM patients. Serum ferritin, malondialdehyde (MDA), liver profiles, triglycerides levels, and VLDL-C were significantly higher while total cholesterol, low-density lipoprotein cholesterol, high density lipoprotein cholesterol and total antioxidant capacity were lower in ?-TM than controls. Serum ferritin was significantly correlated with MDA, liver enzymes and lipid profiles (p < 0.05). Multiple forward stepwise linear regression analyses of the significant variables showed that in these ?-TM patients, independent predictors of iron overload were MDA (? = 0.410, r (2) = 0.671, p < 0.001), ALT (? = 0.493, r (2) = 0.578, p < 0.001), and VLDL-C (? = 0.253, r (2) = 0.711, p < 0.001). In conclusion, iron overload associated with increased oxidative stress, lipid peroxidation, liver damage, decreased TC, LDL-C, HDL-C and over production of VLDL-C, is significantly problem in transfusion-dependent ?-TM patients. These appeared the major cause of future morbidity and mortality in ?-TM patients. PMID:24966477

  6. The involvement of Nrf2 in the protective effects of diallyl disulfide on carbon tetrachloride-induced hepatic oxidative damage and inflammatory response in rats.

    PubMed

    Lee, In-Chul; Kim, Sung-Hwan; Baek, Hyung-Seon; Moon, Changjong; Kang, Seong-Soo; Kim, Sung-Ho; Kim, Yun-Bae; Shin, In-Sik; Kim, Jong-Choon

    2014-01-01

    This study investigated the potential effect of diallyl disulfide (DADS) against carbon tetrachloride (CCl4)-induced oxidative hepatic damage and inflammatory response in rat liver. DADS at doses of 50 and 100 mg/kg/day was administered orally once daily for 5 days, prior to CCl4 administration. Pretreatment with DADS attenuated CCl4-induced elevated serum transaminase activities and histopathological alterations in liver. It prevented the hepatocellular apoptotic changes with induction of Bcl-2-associated X (Bax), cytochrome c, and caspase-3 caused by CCl4. An increase in the nuclear translocation of nuclear factor-kappaB (NF-?B) and phosphorylation of I kappaB alpha (I?B?) was observed in the livers of CCl4-treated rats that coincided with induction of inflammatory mediators or cytokines. In contrast, DADS inhibited NF-?B translocation and I?B? phosphorylation, and that subsequently decreased inflammatory mediators. Furthermore, DADS prevented CCl4-induced depletion of cytosolic nuclear factor E2-related factor 2 (Nrf2) and suppression of nuclear translocation of Nrf2, which, in turn, up-regulated phase II/antioxidant enzyme activities. Taken together, these results demonstrate that DADS increases the expression of phase II/antioxidant enzymes and simultaneously decreases the expression of inflammatory mediators in CCl4-induced liver injury. These findings indicate that DADS induces antioxidant defense mechanism by activating Nrf2 pathway and reduces inflammatory response by inhibiting NF-?B activation. PMID:24246655

  7. Ethanol toxicity: rehabilitation of hepatic antioxidant defense system with dietary ginger.

    PubMed

    Mallikarjuna, K; Sahitya Chetan, P; Sathyavelu Reddy, K; Rajendra, W

    2008-04-01

    The current investigation has been conducted to investigate the influence of ginger on hepatic antioxidant enzymes system in ethanol treated rats. Ethanol significantly decreased the superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione content while an increase of malondialdehyde (MDA) levels were estimated in the hepatic tissue. This effect was reversed by a treatment with 1% dietary ginger for 4 weeks in rats by improved antioxidant status which suggest that treatment of ginger may have protective role against the ethanol induced hepatotoxicity. PMID:18182172

  8. Sustained antagonism of acute ethanol-induced ataxia following microinfusion of cyclic AMP and cpt-cAMP in the mouse cerebellum.

    PubMed

    Dar, M Saeed

    2011-05-01

    Ataxia is a conspicuous physical manifestation of alcohol consumption in humans and laboratory animals. Previously we reported possible involvement of cAMP in ethanol-induced ataxia. We now report a sustained antagonism of ataxia due to multiple ethanol injections following intracerebellar (ICB) cAMP or cpt-cAMP microinfusion. Adenylyl cyclase drugs cAMP, cpt-cAMP, Sp-cAMP, Rp-cAMP, adenosine A? agonist, N?-cyclohexyladenosine (CHA) and GABA(A) agonist muscimol were directly microinfused into the cerebellum of CD-1 male mice to evaluate their effect on ethanol (2 g/kg; i.p.) ataxia. Drug microinfusions were made via stereotaxically implanted stainless steel guide cannulas. Rotorod was used to evaluate the ethanol's ataxic response. Intracerebellar cAMP (0.1, 1, 10 fmol) or cpt-cAMP (0.5, 1, 2 fmol) 60 min before ethanol treatment, dose-dependently attenuated ethanol-induced ataxia in general agreement with previous observations. Intracerebellar microinfusion of cAMP (100 fmol) or cpt-cAMP (2 fmol) produced a sustained attenuation of ataxia following ethanol administration at 1, 4, 7 and 25 h or 31 h post-cAMP/cpt-cAMP microinfusion. At 31 h post-cAMP, the ataxic response of ethanol reappeared. Additionally, marked antagonism to the accentuation of ethanol-induced ataxia by adenosine A? and GABA(A) agonists, CHA (34 pmol) and muscimol (88 pmol), respectively, was noted 24h after cAMP and cpt-cAMP treatment. This indicated possible participation of AC/cAMP/PKA signaling in the co-modulation of ethanol-induced ataxia by A? adenosinergic and GABAergic systems. No change in normal motor coordination was noted when cAMP or cpt-cAMP microinfusion was followed by saline. Finally, Rp-cAMP (PKA inhibitor, 22 pmol) accentuated ethanol-induced ataxia and antagonized its attenuation by cAMP whereas Sp-cAMP (PKA activator, 22 pmol) produced just the opposite effects, further indicating participation of cAMP-dependent PKA downstream. Overall, the results support a role of AC/cAMP/PKA signaling in the expression of ethanol-induced ataxia and its co-modulation by adenosine A? and GABA(A) receptors. PMID:21192968

  9. Supplementation of Citrus maxima Peel Powder Prevented Oxidative Stress, Fibrosis, and Hepatic Damage in Carbon Tetrachloride (CCl4) Treated Rats

    PubMed Central

    Chowdhury, Mohammed Riaz Hasan; Sagor, Md Abu Taher; Tabassum, Nabila; Potol, Md Abdullah

    2015-01-01

    Citrus maxima peel is rich in natural phenolic compounds and has a long use in the traditional medicine. HPLC-DAD analysis on Citrus maxima peel powder exhibited the presence of various phenolic compounds such as caffeic acid and (?)-epicatechin. To determine the plausible hepatoprotective activity of Citrus maxima peel powder, we used carbon tetrachloride (CCl4) treated rat model. Liver damage in rats was confirmed by measuring the AST, ALT, and ALP enzyme activities. In addition, lipid peroxidation products (MDA), nitric oxide, advanced protein oxidation products level (APOP), and catalase activities were also analyzed along with the histological profiling for the inflammatory cell infiltration, collagen, and iron deposition in liver. Dietary supplementation of Citrus maxima peel powder exhibited significant reduction of serum AST, ALT, and ALP activities in carbon tetrachloride treated rats. Moreover, Citrus maxima peel powder also showed a significant reduction of the oxidative stress markers (MDA, NO, and APOP level) and restored the catalase activity in CCl4 treated rats. Histological examination of the liver section revealed reduced inflammatory cells infiltration, collagen, and iron deposition in CCl4 treated rats. The results from this study demonstrated that Citrus maxima peel powder produced significant hepatoprotective action in CCl4 administered rats.

  10. Intragastric nicotine protects against 40% ethanol-induced gastric injury despite pretreatment with NG-nitro-L-arginine methyl ester or adrenal medullectomy in rats.

    PubMed

    Iwata, F; Endoh, K; Leung, F W

    1994-02-01

    We tested the hypotheses that the protective effect of intragastric nicotine against ethanol-induced gastric mucosal injury is dependent on endogenous nitric oxide or peripheral sympathoadrenal mechanisms. Rats were pretreated with NG-nitro-L-arginine methyl ester (3 mg/kg subcutaneous, 1 h prior to study) to block endogenous nitric oxide synthesis or with adrenal medullectomy (three weeks prior to study) to ablate the effect of the adrenal medulla. At 1-h intervals, vehicle or nicotine (4 mg/kg) and 40% ethanol were then given intragastrically. The total lengths of the linear gastric corpus mucosal lesions were measured unbiasedly. The protective effect of intragastric nicotine was not modified by either pretreatment. We conclude that the mechanism mediating intragastric nicotine protection against 40% ethanol-induced gastric mucosal injury is independent of endogenous nitric oxide or the adrenal medulla. PMID:8313817

  11. Effects of zincl-carnosine on gastric mucosal and cell damage caused by ethanol in rats

    Microsoft Academic Search

    Tetsuo Arakawa; Hiroshi Satoh; Atsushi Nakamura; Hiroko Nebiki; Takashi Fukuda; Hiroyuki Sakuma; Hajime Nakamura; Mikio Ishikawa; Masao Seiki; Kenzo Kobayashi

    1990-01-01

    The effects of zincl-carnosine on ethanol-induced damage and the correlation of these effects with endogenous prostaglandin E2 were evaluated in rat gastric mucosain vivo andin vivo. When given either intragastrically or intraperitoneally, zincl-carnosine (10 or 30 mg\\/kg) prevented gross visible damage to gastric mucosa caused by ethanol without affecting the mucosal prostaglandin E2 level. This protective effect of zincl-carnosine was

  12. Urinary concentrations of ethyl glucuronide and ethyl sulfate as thresholds to determine potential ethanol-induced alteration of steroid profiles.

    PubMed

    Thieme, D; Grosse, J; Keller, L; Graw, M

    2011-01-01

    The suppression of steroid biotransformation resulting in a decrease of the major urinary metabolites--androsterone and etiocholanolone--and the elevation of testosterone/epitestosterone (T/E) ratios following ethanol administration is well described. At least the latter parameter T/E represents an important indicator for endogenous steroid abuse in doping control. The quantitative correlation between ethanol consumption markers and steroid profile alteration was evaluated, aiming to differentiate between permitted ethanol administration and potential steroid abuse. Steroid profiles, ethanol, ethyl glucuronide (EtG), and sulfate (EtS) were quantified after administration of ethanol (intended maximum ethanol concentration in blood was 1 mg/g) to 21 male and 15 female volunteers. EtG concentrations in urine (corrected by either specific gravity or creatinine concentration) were found to be most suitable for quantitative evaluations. Gender specific urinary EtG concentrations of 48 ug/ml (men) and 15.5 ug/ml (women) may be considered as useful thresholds for a potential ethanol-induced suppression of steroids biotransformation. PMID:22213685

  13. Prediction of deleterious non-synonymous single nucleotide polymorphisms of genes related to ethanol-induced toxicity.

    PubMed

    Wang, Lin-Lin; Li, Yong; Zhou, Shu-Feng

    2009-06-01

    Non-synonymous single nucleotide polymorphisms (nsSNPs) that cause amino acid changes are believed to have a large impact on protein function. It is important to distinguish those deleterious nsSNPs that affect protein function from those that are functionally neutral. Ethanol causes organ toxicity with involvement of a number of genes encoding functional proteins. We have identified 1509 alcohol-responsive genes after a systemic search of previous human studies, with 580 being up-regulated and 847 down-regulated. The samples for gene expression analysis of ethanol exposure are from the brain, liver, and cultured human cells. These genes mainly encode proteins involved in nucleic acid binding, transcription, and signal transduction. These ethanol-responsive genes also correlated with other biological pathways, such as angiogenesis, integrin signalling pathway, and inflammation. The number of nsSNPs in the 1509 validated alcohol-responsive genes was 9207. Using the PolyPhen and SIFT algorithms, 41.5% nsSNPs were predicted to be deleterious. These findings provide some insights into the molecular targets of ethanol-induced toxicity and how genetic mutation would affect the toxicity phenotype. A better understanding of the relationship between genotype and phenotype of nsSNPs of ethanol-responsive genes will provide useful hints for further research on alcohol-induced toxicity and potential therapy. PMID:19429251

  14. POST-RETRIEVAL PROPRANOLOL TREATMENT DOES NOT MODULATE RECONSOLIDATION OR EXTINCTION OF ETHANOL-INDUCED CONDITIONED PLACE PREFERENCE

    PubMed Central

    Font, Laura; Cunningham, Christopher L.

    2012-01-01

    The reconsolidation hypothesis posits that established emotional memories, when reactivated, become labile and susceptible to disruption. Post-retrieval injection of propranolol (PRO), a nonspecific ?-adrenergic receptor antagonist, impairs subsequent retention performance of a cocaine- and a morphine-induced conditioned place preference (CPP), implicating the noradrenergic system in the reconsolidation processes of drug-seeking behavior. An important question is whether post-retrieval PRO disrupts memory for the drug-cue associations, or instead interferes with extinction. In the present study, we evaluated the role of the ?-adrenergic system on the reconsolidation and extinction of ethanol-induced CPP. Male DBA/2J mice were trained using a weak or a strong conditioning procedure, achieved by varying the ethanol conditioning dose (1 or 2 g/kg) and the number of ethanol trials (2 or 4). After acquisition of ethanol CPP, animals were given a single post-retrieval injection of PRO (0, 10 or 30 mg/kg) and tested for memory reconsolidation 24 h later. Also, after the first reconsolidation test, mice received 18 additional 15-min choice extinction tests in which PRO was injected immediately after every test. Contrary to the prediction of the reconsolidation hypothesis, a single PRO injection after the retrieval test did not modify subsequent memory retention. In addition, repeated post-retrieval administration of PRO did not interfere with extinction of CPP in mice. Overall, our data suggest that the ?-adrenergic receptor does not modulate the associative processes underlying ethanol CPP. PMID:22285323

  15. KNOCKDOWN OF GCN5 HISTONE ACETYLTRANSFERASE by siRNA DECREASES ETHANOL INDUCED HISTONE ACETYLATION AND AFFECTS DIFFERENTIAL EXPRESSION OF GENES IN HUMAN HEPATOMA CELLS

    PubMed Central

    Choudhury, Mahua; Pandey, Ravi S.; Clemens, Dahn L.; Davis, J. Wade; Lim, Robert W.; Shukla, Shivendra D.

    2011-01-01

    We have investigated whether Gcn5, a histone acetyltransferase (HAT), is involved in ethanol induced acetylation of histone H3 at lysine 9 (H3AcK9) and has any effect on the gene expression. Human hepatoma HepG2 cells transfected with ethanol metabolizing enzyme alcohol dehydrogenase 1 (VA 13 cells) were used. Knockdown of Gcn5 by siRNA silencing decreased mRNA and protein levels of GCN5, HAT activity, and also attenuated ethanol induced H3AcK9 in VA13 cells. Illumina gene microarray analysis using total RNA showed 940 transcripts affected by GCN5 silencing or ethanol. Silencing caused differential expression of 891 transcripts (? 1.5 fold up- or down- regulated). Among these, 492 transcripts were up- and 399 were down- regulated compared to their respective controls. Using a more stringent threshold (? 2.5 fold) the array data from GCN5 silenced samples showed 57 genes differentially expressed (39 up-regulated and 18 down-regulated). Likewise, ethanol caused differential regulation of 57 transcripts with ? 1.5 fold change (35 gene up-regulated and 22 down-regulated). Further analysis showed that eight genes were differentially regulated that were common for both ethanol treatment and GCN5 silencing. Among these, SLC44A2 (a putative choline transporter) was strikingly up-regulated by ethanol (3 fold), and GCN5 silencing down regulated it (1.5 fold). The quantitative RT-PCR profile corroborated the array findings. This report demonstrates for the first time that (a) GCN5 differentially affects expression of multiple genes, (b) ethanol induced histone H3-lysine 9 acetylation is mediated via GCN5 and (c) that GCN5 is involved in ethanol induced expression of the putative choline transporter SLC44A2. PMID:21367571

  16. Antilipogenic and Anti-Inflammatory Activities of Codonopsis lanceolata in Mice Hepatic Tissues after Chronic Ethanol Feeding

    PubMed Central

    Cha, Areum; Choi, Youngshim; Jin, Yoojeong; Sung, Mi-Kyung; Koo, Yun-Chang; Lee, Kwang-Won; Park, Taesun

    2012-01-01

    This study evaluated the antilipogenic and anti-inflammatory effects of Codonopsis lanceolata (C. lanceolata) root extract in mice with alcohol-induced fatty liver and elucidated its underlying molecular mechanisms. Ethanol was introduced into the liquid diet by mixing it with distilled water at 5% (wt/v), providing 36% of the energy, for nine weeks. Among the three different fractions prepared from the C. lanceolata root, the C. lanceolata methanol extract (CME) exhibited the most remarkable attenuation of alcohol-induced fatty liver with respect to various parameters such as hepatic free fatty acid concentration, body weight loss, and hepatic accumulations of triglyceride and cholesterol. The hepatic gene and protein expression levels were analysed via RT-PCR and Western blotting, respectively. CME feeding significantly restored the ethanol-induced downregulation of the adiponectin receptor (adipoR) 1 and of adipoR2, along with their downstream molecules. Furthermore, the study data showed that CME feeding dramatically reversed ethanol-induced hepatic upregulation of toll-like receptor- (TLR-) mediated signaling cascade molecules. These results indicate that the beneficial effects of CME against alcoholic fatty livers of mice appear to be with adenosine- and adiponectin-mediated regulation of hepatic steatosis and TLR-mediated modulation of hepatic proinflammatory responses. PMID:22013387

  17. Calpain and lipopolysaccharide mediated hepatitis 

    E-print Network

    Rose, Robert Edward

    2009-06-02

    This study tested the role of the calcium dependent cytosolic protein calpain in neutrophilic hepatitis. We hypothesized that inhibition of calpain would protect against LPS-induced neutrophilic liver damage. To test our hypothesis, a reliable LPS...

  18. Viral Hepatitis

    MedlinePLUS

    ... hepatitis B immune globulin (H-BIG) and the hepatitis B vaccine within 12 hours after birth. If you have ... liver disease All children at age 1 The hepatitis B vaccine is usually given in three doses over six ...

  19. Unilateral whisker clipping exacerbates ethanol-induced social and somatosensory behavioral deficits in a sex- and age-dependent manner.

    PubMed

    Wellmann, Kristen A; Mooney, Sandra M

    2015-09-01

    Prenatal exposure to ethanol results in sensory deficits and altered social interactions in animal and clinical populations. Sensory stimuli serve as important cues and shape sensory development; developmental exposure to ethanol or sensory impoverishment can impair somatosensory development, but their combined effects on behavioral outcomes are unknown. We hypothesized 1) that chronic prenatal ethanol exposure would disrupt social interaction and somatosensory performance during adolescence, 2) that a mild sensory impoverishment (neonatal unilateral whisker clipping; WC) would have a mildly impairing to sub-threshold effect on these behavioral outcomes, and 3) that the effect of ethanol would be exacerbated by WC. Long-Evans dams were fed a liquid diet containing ethanol or pair-fed with a non-ethanol diet on gestational days (G) 6-G21. Chow-fed control animals were also included. One male and female pup per litter underwent WC on postnatal day (P)1, P3, and P5. Controls were unclipped. Offspring underwent social interaction on P28 or P42, and gap-crossing (GC) on P31 or P42. Ethanol-exposed pups played less and crossed shorter gaps than control pups regardless of age or sex. WC further exacerbated ethanol-induced play fighting and GC deficits in all males but only in 28-day-old females. WC alone reduced sniffing in all males and in younger females. Thus, prenatal ethanol exposure induced deficits in social interaction and somatosensory performance during adolescence. Sensory impoverishment exacerbates ethanol's effect in 28-day-old male and female animals and in 42-day-old males, suggesting sex- and age-dependent changes in outcomes in ethanol-exposed offspring. PMID:25283794

  20. Presynaptic BK Channels Modulate Ethanol-Induced Enhancement of GABAergic Transmission in the Rat Central Amygdala Nucleus

    PubMed Central

    Li, Qiang; Madison, Roger

    2014-01-01

    Large-conductance calcium-activated potassium BK channels are widely expressed in the brain and are involved in the regulation of neuronal functions such as neurotransmitter release. However, their possible role in mediating ethanol-induced GABA release is still unknown. We assessed the role of BK channels in modulating the action of ethanol on inhibitory synaptic transmission mediated via GABAA receptors in the rat central nucleus of the amygdala (CeA). Evoked IPSCs (eIPSCs) mediated by GABAA receptors were isolated from CeA neurons under whole-cell voltage clamp, and their response to selective BK channel antagonists, channel activators, or ethanol was analyzed. Blocking BK channels with the specific BK channel antagonist paxilline significantly increased the mean amplitude of eIPSCs, whereas the activation of BK channels with the channel opener NS1619 reversibly attenuated the mean amplitude of eIPSCs. Ethanol (50 mm) alone enhanced the amplitude of eIPSCs but failed to further enhance eIPSCs in the slices pretreated with paxilline. Bath application of either BK channel blockers significantly increased the frequency of miniature IPSCs (mIPSCs). Similarly, 50 mm ethanol alone also enhanced mIPSC frequency. Increases in mIPSC frequency by either selective BK channel antagonists or ethanol were not accompanied with changes in the amplitude of mIPSCs. Furthermore, following bath application of BK channel blockers for 10 min, ethanol failed to further increase mIPSC frequency. Together, these results suggest that blocking BK channels mimics the effects of ethanol on GABA release and that presynaptic BK channels could serve as a target for ethanol effects in CeA. PMID:25297098

  1. Hepatitis regulation by the inflammasome signaling pathway.

    PubMed

    Negash, Amina A; Gale, Michael

    2015-05-01

    Hepatitis is damage and inflammation of the liver. It is triggered by both environmental and endogenous insults and is a platform for developing liver cirrhosis and cancer. Both innate and adaptive immune activation contribute to hepatic inflammation and disease. Viral hepatitis is the most common form of hepatitis and is typically associated with chronic viral infection. Alcohol-induced and non-alcoholic steatohepatitis are two rising hepatic problems. The innate immune inflammasome signaling cascade mediates the production of essential proinflammatory cytokines interleukin-1? (IL-1?) and IL-18. These cytokines regulate hepatic cell interaction and crosstalk of the various inflammatory pathways and influence disease outcome. PMID:25879290

  2. Hepatitis C and HIV

    MedlinePLUS

    ... Potential Related Health Problems Opportunistic Infections Hepatitis A Hepatitis B Hepatitis C Tuberculosis Oral Health Issues Cancer Cardiovascular ... of viral hepatitis are hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV). HBV ...

  3. Hepatitis B and HIV

    MedlinePLUS

    ... Health Problems : Hepatitis B Translate Text Size Print Hepatitis B What is Hepatitis? Hepatitis means inflammation of the liver. This condition ... our related pages, Hepatitis A and Hepatitis C . Hepatitis B and HIV About 10% of people living ...

  4. The Pro-Apoptotic BH3-only, Bcl-2 Family Member Puma Is Critical for Acute Ethanol-Induced Neuronal Apoptosis

    PubMed Central

    Ghosh, Arindam P.; Walls, Ken C.; Klocke, Barbara J.; Toms, Rune; Strasser, Andreas; Roth, Kevin A.

    2009-01-01

    Synaptogenesis in humans occurs in the last trimester of gestation and in the first few years of life whereas it occurs in the postnatal period in rodents. A single exposure of neonatal rodents to ethanol during this period evokes extensive neuronal apoptosis. Previous studies indicate that ethanol triggers the intrinsic apoptotic pathway in neurons and that this requires the multi-BH domain, pro-apoptotic Bcl-2 family member Bax. To define the upstream regulators of this apoptotic pathway, we examined the possible roles of p53 and a subclass of pro-apoptotic Bcl-2 family members (i.e. the BH3 domain-only proteins) in neonatal wild-type and gene-targeted mice that lack these cell death inducers. Acute ethanol exposure produced greater caspase-3 activation and neuronal apoptosis in wild type mice than in saline-treated littermate controls. Loss of Puma resulted in marked protection from ethanol-induced caspase-3 activation and apoptosis. Although Puma expression has been reported to be regulated by p53, p53-deficient mice exhibited a similar extent of ethanol-induced caspase-3 activation and neuronal apoptosis as wild-type mice. Mice deficient in other pro-apoptotic BH3-only proteins, including Noxa, Bim or Hrk, showed no significant protection from ethanol-induced neuronal apoptosis. Collectively, these studies indicate a p53-independent, Bax- and Puma-dependent mechanism of neuronal apoptosis and identify Puma as a possible molecular target for inhibiting the effects of intrauterine ethanol exposure in humans. PMID:19535997

  5. Cytokines and chemokines as biomarkers of ethanol-induced neuroinflammation and anxiety-related behavior: role of TLR4 and TLR2.

    PubMed

    Pascual, María; Baliño, Pablo; Aragón, Carlos M G; Guerri, Consuelo

    2015-02-01

    Recent evidence supports the influence of neuroimmune system activation on behavior. We have demonstrated that ethanol activates the innate immune system by stimulating toll-like receptor 4 (TLR4) signaling in glial cells, which triggers the release of inflammatory mediators and causes neuroinflammation. The present study aimed to evaluate whether the ethanol-induced up-regulation of cytokines and chemokines is associated with anxiety-related behavior, 24 h after ethanol removal, and if TLR4 or TLR2 is involved in these effects. We used WT, TLR4-KO and TLR2-KO mice treated with alcohol for 5 months to show that chronic ethanol consumption increases the levels of cytokines (IL-1?, IL-17, TNF-?) and chemokines (MCP-1, MIP-1?, CX3CL1) in the striatum and serum (MCP-1, MIP-1?, CX3CL1) of WT mice. Alcohol deprivation for 24 h induces IFN-? levels in the striatum and maintains high levels of some cytokines (IL-1?, IL-17) and chemokines (MIP-1?, CX3CL1) in this brain region. The latter events were associated with an increase in anxiogenic-related behavior, as evaluated by the dark and light box and the elevated plus maze tests. Notably, mice lacking TLR4 or TLR2 receptors are largely protected against ethanol-induced cytokine and chemokine release, and behavioral associated effects during alcohol abstinence. These data support the role of TLR4 and TLR2 responses in neuroinflammation and in anxiogenic-related behavior effects during ethanol deprivation, and also provide evidence that chemokines and cytokines can be biomarkers of ethanol-induced neuroimmune response. PMID:25446779

  6. Relationship between ethanol-induced activity and anxiolysis in the open field, elevated plus maze, light-dark box, and ethanol intake in adolescent rats

    PubMed Central

    Acevedo, María Belén; Nizhnikov, Michael E.; Molina, Juan C.; Pautassi, Ricardo Marcos

    2014-01-01

    It is yet unclear if ethanol-induced motor stimulation in the open field (OF) merely reflects psychomotor stimulating effects of the drug or if this stimulation is driven or modulated by ethanol’s antianxiety properties. In the present study, adolescent rats were administered with different ethanol doses or remained untreated. They were sequentially assessed in the OF, elevated plus maze (EPM), and light-dark box (LDB) and then assessed for ethanol intake. The aims were to assess the relationship between measures of ethanol-induced activity and anxiolysis, analyze ethanol intake as a function of prior ethanol exposure, and associate behavioral responsiveness in these apparatus with ethanol intake during adolescence. The results suggested that the enhanced exploration of the OF observed after 2.5 and 3.25 g/kg ethanol reflected a motor-stimulating effect that appeared to be relatively independent of anxiolysis. The 1.25 g/kg dose induced motor stimulation in the OF and anti-anxiety effects in the EPM, but these effects were relatively independent. The 0.5 g/kg ethanol dose exerted significant anxiolytic effects in the EPM in the absence of stimulating effects in the OF. A multivariate regression analysis indicated that adolescents with a higher frequency of rearing behavior in the OF, higher percentage of open arm entries in the EPM, and lower propensity to enter the central area of the OF exhibited greater ethanol intake. These results indicate that the OF is a valid procedure for the measurement of ethanol-induced stimulation, and provide information towards characterizing subpopulations of adolescents at risk for initiating alcohol drinking. PMID:24583190

  7. Hepatoprotective Activity of Elephantopus scaber on Alcohol-Induced Liver Damage in Mice

    PubMed Central

    Ho, Wan Yong; Yeap, Swee Keong; Ho, Chai Ling; Abdul Rahim, Raha; Alitheen, Noorjahan Banu

    2012-01-01

    Elephantopus scaber has been traditionally used as liver tonic. However, the protective effect of E. scaber on ethanol-induced liver damage is still unclear. In this study, we have compared the in vivo hepatoprotective effect of E. scaber with Phyllanthus niruri on the ethanol-induced liver damage in mice. The total phenolic and total flavanoid content of E. scaber ethanol extract were determined in this study. Accelerating serum biochemical profiles (including AST, ALT, ALP, triglyceride, and total bilirubin) associated with fat drop and necrotic body in the liver section were observed in the mice treated with ethanol. Low concentration of E. scaber was able to reduce serum biochemical profiles and the fat accumulation in the liver. Furthermore, high concentration of E. scaber and positive control P. niruri were able to revert the liver damage, which is comparable to the normal control. Added to this, E. scaber did not possess any oral acute toxicity on mice. These results suggest the potential effect of this extract as a hepatoprotective agent towards-ethanol induced liver damage without any oral acute toxicity effect. These activities might be contributed, or at least in part, by its high total phenolic and flavonoid contents. PMID:22973401

  8. ETHANOL INDUCES AND INSULIN INHIBITS ALCOHOL DEHYDROGENASE CLASS 1 IN FGC-4 CELLS: BOTH APPEAR TO WORK THROUGH SREBP-1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have previously reported that chronic feeding of alcohol-containing diets (via intragastric infusion) to Sprague-Dawley rats induces hepatic alcohol dehydrogenase (ADH) Class 1 by interfering with signaling via the sterol regulatory element binding protein (SREBP-1). We have studied the effects ...

  9. Oxidative damage to the hepatocellular proteins after chronic ethanol intake in the rat

    Microsoft Academic Search

    Premila Abraham; G Wilfred; Banumathi Ramakrishna

    2002-01-01

    Background: Protein carbonyl content, a measure of oxidative damage to hepatocellular proteins, and the activities of some thiol-containing proteins were assayed in the liver and plasma, as thiol-containing protein, appear to be targets for free radicals. These may be important in the mechanism of ethanol-induced liver injury. Methods: Tap water containing ethanol at the concentration of 25% (v\\/v) and phenobarbital

  10. Gastroprotective Effects of Lion's Mane Mushroom Hericium erinaceus (Bull.:Fr.) Pers. (Aphyllophoromycetideae) Extract against Ethanol-Induced Ulcer in Rats.

    PubMed

    Wong, Jing-Yang; Abdulla, Mahmood Ameen; Raman, Jegadeesh; Phan, Chia-Wei; Kuppusamy, Umah Rani; Golbabapour, Shahram; Sabaratnam, Vikineswary

    2013-01-01

    Hericium erinaceus is a famous tonic in oriental medicine. The gastroprotective effects of aqueous extract of H. erinaceus against ethanol-induced ulcers in Sprague Dawley rats were investigated. The possible involvements of lipid peroxidation, superoxide dismutase, and catalase were also investigated. Acute toxicity study was performed. The effects of aqueous extract of H. erinaceus on the ulcer areas, ulcer inhibition, gastric wall mucus, gross and histological gastric lesions, antioxidant levels, and malondialdehyde (MDA) contents were evaluated in ethanol-induced ulcer in vivo. In acute toxicity study, a high dose of 5?g/kg did not manifest any toxicological signs in rats. The extract promoted ulcer protection as ascertained by a significant reduction of the ulcer area. Furthermore, it exhibited a significant protection activity against gastric mucosal injury by preventing the depletion of antioxidant enzymes. The level of MDA was also limited in rat stomach tissues when compared with the ulcer control group. Immunohistochemistry showed upregulation of HSP70 protein and downregulation of BAX protein in rats pretreated with the extract. The aqueous extract of H. erinaceus protected gastric mucosa in our in vivo model. It is speculated that the bioactive compounds present in the extract may play a major role in gastroprotective activity. PMID:24302966

  11. Korean Red Ginseng attenuates ethanol-induced steatosis and oxidative stress via AMPK/Sirt1 activation

    PubMed Central

    Han, Jae Yun; Lee, Sangkyu; Yang, Ji Hye; Kim, Sunju; Sim, Juhee; Kim, Mi Gwang; Jeong, Tae Cheon; Ku, Sae Kwang; Cho, Il Je; Ki, Sung Hwan

    2014-01-01

    Background Alcoholic steatosis is the earliest and most common liver disease, and may precede the onset of more severe forms of liver injury. Methods The effect of Korean Red Ginseng extract (RGE) was tested in two murine models of ethanol (EtOH)-feeding and EtOH-treated hepatocytes. Results Blood biochemistry analysis demonstrated that RGE treatment improved liver function. Histopathology and measurement of hepatic triglyceride content verified the ability of RGE to inhibit fat accumulation. Consistent with this, RGE administration downregulated hepatic lipogenic gene induction and restored hepatic lipolytic gene repression by EtOH. The role of oxidative stress in the pathogenesis of alcoholic liver diseases is well established. Treatment with RGE attenuated EtOH-induced cytochrome P450 2E1, 4-hydroxynonenal, and nitrotyrosine levels. Alcohol consumption also decreased phosphorylation of adenosine monophosphate-activated protein kinase, which was restored by RGE. Moreover, RGE markedly inhibited fat accumulation in EtOH-treated hepatocytes, which correlated with a decrease in sterol regulatory element-binding protein-1 and a commensurate increase in sirtuin 1 and peroxisome proliferator-activated receptor-? expression. Interestingly, the ginsenosides Rb2 and Rd, but not Rb1, significantly inhibited fat accumulation in hepatocytes. Conclusion These results demonstrate that RGE and its ginsenoside components inhibit alcoholic steatosis and liver injury by adenosine monophosphate-activated protein kinase/sirtuin 1 activation both in vivo and in vitro, suggesting that RGE may have a potential to treat alcoholic liver disease. PMID:26045683

  12. Hepatitis B Vaccine

    MedlinePLUS

    ... as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... Hepatitis B vaccine: Why get vaccinated?Hepatitis B vaccine can prevent hepatitis B, and the serious consequences of hepatitis ...

  13. What Is Hepatitis?

    MedlinePLUS

    ... in a more serious disease and worse outcome. Hepatitis B vaccines provide protection from HDV infection. Hepatitis E virus ( ... agaiin Hepatitis infographics Hepatitis A & E pdf, 90kb Hepatitis B, C, D pdf, ... about hepatitis You are here: Features ...

  14. Apoptotic Damage of Pancreatic Ductal Epithelia by Alcohol and Its Rescue by an Antioxidant

    PubMed Central

    Seo, Jong Bae; Gowda, G. A. Nagana; Koh, Duk-Su

    2013-01-01

    Alcohol abuse is a major cause of pancreatitis. However alcohol toxicity has not been fully elucidated in the pancreas and little is known about the effect of alcohol on pancreatic ducts. We report the molecular mechanisms of ethanol-induced damage of pancreatic duct epithelial cells (PDEC). Ethanol treatment for 1, 4, and 24 h resulted in cell death in a dose-dependent manner. The ethanol-induced cell damage was mainly apoptosis due to generation of reactive oxygen species (ROS), depolarization of mitochondrial membrane potential (MMP), and activation of caspase-3 enzyme. The antioxidant N-acetylcysteine (NAC) attenuated these cellular responses and reduced cell death significantly, suggesting a critical role for ROS. Acetaldehyde, a metabolic product of alcohol dehydrogenase, induced significant cell death, depolarization of MMP, and caspase-3 activation as ethanol and this damage was also averted by NAC. Reverse transcription-polymerase chain reaction revealed the expression of several subtypes of alcohol dehydrogenase and acetaldehyde dehydrogenase. Nuclear magnetic resonance spectroscopy data confirmed the accumulation of acetaldehyde in ethanol-treated cells, suggesting that acetaldehyde formation can contribute to alcohol toxicity in PDEC. Finally, ethanol increased the leakage of PDEC monolayer which was again attenuated by NAC. In conclusion, ethanol induces apoptosis of PDEC and thereby may contribute to the development of alcohol-induced pancreatitis. PMID:24244749

  15. ETHANOL INDUCES RAT HEPATIC ALCOHOL DEHYDROGENASE (ADH) CLASS I BY INTERFERING WITH POST-TRANSLATIONAL REGULATION OF STEROL REGULATORY ELEMENT BINDING PROTEIN-1 (SREBP-1)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Continuous infusion of ethanol into the stomach of nutritionally supported rats results in pulses of blood and urine ethanol with a 6-7 day cycle rather than the steady-state normally observed with chronically infused drugs. The cycle is driven by cyclical changes in transcription of liver ADH Class...

  16. Hepatitis A

    MedlinePLUS

    ... an inflammation of the liver. One type, hepatitis A, is caused by the hepatitis A virus (HAV). The disease spreads through contact with ... washed in untreated water Putting into your mouth a finger or object that came into contact with ...

  17. Hepatitis B

    MedlinePLUS

    ... times more infectious than HIV. Which adults need hepatitis B vaccine? Any sexually active adult who is not in ... share needles, syringes, or other drug-injection equipment. Hepatitis B vaccine is available alone or in a combination with ...

  18. Hepatic Cysts.

    PubMed

    Kaul; Friedenberg; Rothstein

    2000-12-01

    Treatment of hepatic cysts should be considered only for those patients who are symptomatic. For simple cysts, percutaneous aspiration invariably leads to recurrence; laparoscopic deroofing is usually curative. Open deroofing (fenestration) should be reserved for cysts inaccessible by laparoscopy. Percutaneous instillation of sclerosing agents (ethanol, iophendylate, minocycline) into nonbiliary and nonparasitic cysts is an alternative therapeutic option in certain cases. Due to increased morbidity, hepatic resection should be reserved for polycystic liver disease, diffuse hepatic involvement, or recurrence after a deroofing procedure. Patients with congenital fibropolycystic disorders (eg, congenital hepatic fibrosis) with evidence of hepatic decompensation, should be considered for liver transplantation. For hepatic hydatid cysts, simple cystectomy or the PAIR (puncture, aspirate, inject, and reaspirate) technique with albendazole treatment have been shown to be equally successful. In the case of alveolar echinococcosis, hepatic resection and liver transplantation are the only effective modalities for localized and extensive hepatic disease, respectively. PMID:11096603

  19. Autoimmune hepatitis

    MedlinePLUS

    Lupoid hepatitis; Chronic acute liver disease ... This form of hepatitis is an autoimmune disease . The body's immune system cannot tell the difference between healthy body tissue and harmful, outside ...

  20. Hepatic ischemia

    MedlinePLUS

    Hepatic ischemia is a condition in which the liver does not get enough blood or oxygen, causing ... blood pressure from any condition can lead to hepatic ischemia. Such conditions may include: Abnormal heart rhythms ...

  1. Case Report: Concurrent Emergence of Hepatitis B e Antigen-Negative Hepatitis B Virus Variant and Autoimmune Hepatitis Cured by Adenine Arabinoside Monophosphate

    Microsoft Academic Search

    Hakim Becheur; Dominique Valla; Marie-Anne Loriot; Alain Attar; Francis Bloch; Jean-Pierre Petite

    1998-01-01

    The hepatitis B virus (HBV) is thought not to be directly cytopathic; clear evidence exists that a host cytototoxic T-cell response to virus-infected hepatocytes, probably promoted by a defective suppressor T function (1), contributes to liver damage in HBVinfected individuals. Whether infection with hepatotropic viruses does lead to autoimmune hepatitis is unclear, although several cases of its development following hepatitis

  2. MicroRNA-217 Promotes Ethanol-induced Fat Accumulation in Hepatocytes by Down-regulating SIRT1*

    PubMed Central

    Yin, Huquan; Hu, Ming; Zhang, Ray; Shen, Zheng; Flatow, Laura; You, Min

    2012-01-01

    Ethanol-mediated inhibition of hepatic sirtuin 1 (SIRT1) plays a crucial role in the pathogenesis of alcoholic fatty liver disease. Here, we investigated the underlying mechanisms of this inhibition by identifying a new hepatic target of ethanol action, microRNA-217 (miR-217). The role of miR-217 in the regulation of the effects of ethanol was investigated in cultured mouse AML-12 hepatocytes and in the livers of chronically ethanol-fed mice. In AML-12 hepatocytes and in mouse livers, chronic ethanol exposure drastically and specifically induced miR-217 levels and caused excess fat accumulation. Further studies revealed that overexpression of miR-217 in AML-12 cells promoted ethanol-mediated impairments of SIRT1 and SIRT1-regulated genes encoding lipogenic or fatty acid oxidation enzymes. More importantly, miR-217 impairs functions of lipin-1, a vital lipid regulator, in hepatocytes. Taken together, our novel findings suggest that miR-217 is a specific target of ethanol action in the liver and may present as a potential therapeutic target for treating human alcoholic fatty liver disease. PMID:22308024

  3. Unlocking the Sporicidal Potential of Ethanol: Induced Sporicidal Activity of Ethanol against Clostridium difficile and Bacillus Spores under Altered Physical and Chemical Conditions

    PubMed Central

    Nerandzic, Michelle M.; Sunkesula, Venkata C. K.; C., Thriveen Sankar; Setlow, Peter; Donskey, Curtis J.

    2015-01-01

    Background Due to their efficacy and convenience, alcohol-based hand sanitizers have been widely adopted as the primary method of hand hygiene in healthcare settings. However, alcohols lack activity against bacterial spores produced by pathogens such as Clostridium difficile and Bacillus anthracis. We hypothesized that sporicidal activity could be induced in alcohols through alteration of physical or chemical conditions that have been shown to degrade or allow penetration of spore coats. Principal Findings Acidification, alkalinization, and heating of ethanol induced rapid sporicidal activity against C. difficile, and to a lesser extent Bacillus thuringiensis and Bacillus subtilis. The sporicidal activity of acidified ethanol was enhanced by increasing ionic strength and mild elevations in temperature. On skin, sporicidal ethanol formulations were as effective as soap and water hand washing in reducing levels of C. difficile spores. Conclusions These findings demonstrate that novel ethanol-based sporicidal hand hygiene formulations can be developed through alteration of physical and chemical conditions. PMID:26177038

  4. Hepatitis B virus infection.

    PubMed

    Trépo, Christian; Chan, Henry L Y; Lok, Anna

    2014-12-01

    Hepatitis B virus infection is a major public health problem worldwide; roughly 30% of the world's population show serological evidence of current or past infection. Hepatitis B virus is a partly double-stranded DNA virus with several serological markers: HBsAg and anti-HBs, HBeAg and anti-HBe, and anti-HBc IgM and IgG. It is transmitted through contact with infected blood and semen. A safe and effective vaccine has been available since 1981, and, although variable, the implementation of universal vaccination in infants has resulted in a sharp decline in prevalence. Hepatitis B virus is not cytopathic; both liver damage and viral control--and therefore clinical outcome--depend on the complex interplay between virus replication and host immune response. Overall, as much as 40% of men and 15% of women with perinatally acquired hepatitis B virus infection will die of liver cirrhosis or hepatocellular carcinoma. In addition to decreasing hepatic inflammation, long-term antiviral treatment can reverse cirrhosis and reduce hepatocellular carcinoma. Development of new therapies that can improve HBsAg clearance and virological cure is warranted. PMID:24954675

  5. Liver ultrastructural morphology and mitochondrial DNA levels in HIV/hepatitis C virus coinfection: no evidence of mitochondrial damage with highly active antiretroviral therapy.

    PubMed

    Matsukura, Motoi; Chu, Fanny F S; Au, May; Lu, Helen; Chen, Jennifer; Rietkerk, Sonja; Barrios, Rolando; Farley, John D; Montaner, Julio S; Montessori, Valentina C; Walker, David C; Côté, Hélène C F

    2008-06-19

    Liver mitochondrial toxicity is a concern, particularly in HIV/hepatitis C virus (HCV) coinfection. Liver biopsies from HIV/HCV co-infected patients, 14 ON-highly active antiretroviral therapy (HAART) and nine OFF-HAART, were assessed by electron microscopy quantitative morphometric analyses. Hepatocytes tended to be larger ON-HAART than OFF-HAART (P = 0.05), but mitochondrial volume, cristae density, lipid volume, mitochondrial DNA and RNA levels were similar. We found no evidence of increased mitochondrial toxicity in individuals currently on HAART, suggesting that concomitant HAART should not delay HCV therapy. PMID:18525271

  6. Ethanol-induced HO-1 and NQO1 Are Differentially Regulated by HIF-1? and Nrf2 to Attenuate Inflammatory Cytokine Expression*

    PubMed Central

    Yeligar, Samantha M.; Machida, Keigo; Kalra, Vijay K.

    2010-01-01

    Oxidative stress plays an important role in alcohol-induced inflammation and liver injury. Relatively less is known about how Kupffer cells respond to oxidative stress-induced expression of heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase (NQO1) to blunt inflammation and liver injury. We showed that Kupffer cells from ethanol-fed rats and ethanol-treated rat Kupffer cells and THP-1 cells displayed increased mRNA expression of HO-1, NQO1, and hypoxia-inducible factor-1? (HIF-1?). Our studies showed that silencing with HIF-1? and JNK-1 siRNAs attenuated ethanol-mediated mRNA expression of HO-1, but not NQO1, whereas Nrf2 siRNA attenuated the mRNA expression of both HO-1 and NQO1. Additionally, JunD but not JunB formed an activator protein-1 (AP-1) oligomeric complex to augment HO-1 promoter activity. Ethanol-induced HO-1 transcription involved antioxidant response elements, hypoxia-response elements, and an AP-1 binding motif in its promoter, as demonstrated by mutation analysis of the promoter, EMSA, and ChIP. Furthermore, livers of ethanol-fed c-Junfl/fl mice showed reduced levels of mRNA for HO-1 but not of NQO1 compared with ethanol-fed control rats, supporting the role of c-Jun or the AP-1 transcriptional complex in ethanol-induced HO-1 expression. Additionally, attenuation of HO-1 levels in ethanol-fed c-Junfl/fl mice led to increased proinflammatory cytokine expression in the liver. These results for the first time show that ethanol regulates HO-1 and NQO1 transcription by different signaling pathways. Additionally, up-regulation of HO-1 protects the liver from excessive formation of inflammatory cytokines. These studies provide novel therapeutic targets to ameliorate alcohol induced inflammation and liver injury. PMID:20833713

  7. Mechanisms for the effects of ethanol on hepatic phosphatidate phosphohydrolase.

    PubMed Central

    Savolainen, M J; Hassinen, I E

    1978-01-01

    1. The effects of the intramuscular administration of glycerol and dihydroxyacetone (40mmol per kg body wt.), sorbitol and glucose (20mmol per kg body wt.) or NaCl (1.5mmol per kg body wt. in 10ml of water per kg body wt.) were investigated on soluble phosphatidate phosphohydrolase and certain metabolites in rat liver. 2. The effects of ethanol and glycerol on phosphatidate phosphohydrolase were also studied in isolated perfused livers. 3. The administration of glycerol, sorbitol and dihydroxyacetone in vivo increased hepatic phosphatidate phosphohydrolase activity by 137, 63 and 32% respectively in 4h. 4. A significant positive correlation was found between the hepatic sn-glycerol 3-phosphate concentration and phosphatidate phosphohydrolase after the administration of various substrates in vivo. 5. The soluble phosphatidate phosphohydrolase activity tended to increase during perfusions of isolated rat livers without added substrates, and neither ethanol nor glycerol produced additional effects. 6. The activity of soluble phosphatidate phosphohydrolase was 2.5 times higher in the livers of hyperthyroid rats than in normal rats. This activity was not influenced by intragastric ethanol or glycerol administration, nor was the concentration of sn-glycerol 3-phosphate changed by these compounds. 7. It is concluded that the ethanol-induced increase in hepatic phosphatidate phosphohydrolase may at least in part be mediated by the hepatic concentration of metabolites, probably by the concentration of sn-glycerol 3-phosphate. PMID:218556

  8. Hepatitis C Test

    MedlinePLUS

    ... Hepatitis C Antibody; Anti-HCV; HCV-PCR; HCV-RNA; Hepatitis C Viral Load Formal name: Viral Hepatitis C Antibody Screen; Viral Hepatitis C RNA by PCR; Hepatitis C Virus Genotype Related tests: ...

  9. Hepatitis virus panel

    MedlinePLUS

    Hepatitis A antibody test; Hepatitis B antibody test; Hepatitis C antibody test; Hepatitis D antibody test ... others through sexual contact or by sharing needles Antibodies to hepatitis C can usually be detected 4 - 10 weeks after ...

  10. Fatty acid ethyl ester synthase inhibition ameliorates ethanol-induced Ca2+-dependent mitochondrial dysfunction and acute pancreatitis

    PubMed Central

    Huang, Wei; Booth, David M; Cane, Matthew C; Chvanov, Michael; Javed, Muhammad A; Elliott, Victoria L; Armstrong, Jane A; Dingsdale, Hayley; Cash, Nicole; Li, Yan; Greenhalf, William; Mukherjee, Rajarshi; Kaphalia, Bhupendra S; Jaffar, Mohammed; Petersen, Ole H; Tepikin, Alexei V; Sutton, Robert; Criddle, David N

    2014-01-01

    Objective Non-oxidative metabolism of ethanol (NOME) produces fatty acid ethyl esters (FAEEs) via carboxylester lipase (CEL) and other enzyme action implicated in mitochondrial injury and acute pancreatitis (AP). This study investigated the relative importance of oxidative and non-oxidative pathways in mitochondrial dysfunction, pancreatic damage and development of alcoholic AP, and whether deleterious effects of NOME are preventable. Design Intracellular calcium ([Ca2+]C), NAD(P)H, mitochondrial membrane potential and activation of apoptotic and necrotic cell death pathways were examined in isolated pancreatic acinar cells in response to ethanol and/or palmitoleic acid (POA) in the presence or absence of 4-methylpyrazole (4-MP) to inhibit oxidative metabolism. A novel in vivo model of alcoholic AP induced by intraperitoneal administration of ethanol and POA was developed to assess the effects of manipulating alcohol metabolism. Results Inhibition of OME with 4-MP converted predominantly transient [Ca2+]C rises induced by low ethanol/POA combination to sustained elevations, with concurrent mitochondrial depolarisation, fall of NAD(P)H and cellular necrosis in vitro. All effects were prevented by 3-benzyl-6-chloro-2-pyrone (3-BCP), a CEL inhibitor. 3-BCP also significantly inhibited rises of pancreatic FAEE in vivo and ameliorated acute pancreatic damage and inflammation induced by administration of ethanol and POA to mice. Conclusions A combination of low ethanol and fatty acid that did not exert deleterious effects per se became toxic when oxidative metabolism was inhibited. The in vitro and in vivo damage was markedly inhibited by blockade of CEL, indicating the potential for development of specific therapy for treatment of alcoholic AP via inhibition of FAEE generation. PMID:24162590

  11. Coenzyme Q10 Rescues Ethanol-induced Corneal Fibroblast Apoptosis through the Inhibition of Caspase-2 Activation*

    PubMed Central

    Chen, Chun-Chen; Liou, Shiow-Wen; Chen, Chi-Chih; Chen, Wen-Chung; Hu, Fung-Rong; Wang, I-Jong; Lin, Shing-Jong

    2013-01-01

    Recent studies indicate that caspase-2 is involved in the early stages of apoptosis, particularly before the occurrence of mitochondrial damage. Here we report the important role of the coenzyme Q10 (CoQ10) on the activity of caspase-2 upstream of mitochondria in ethanol (EtOH)-treated corneal fibroblasts. After EtOH exposure, cells produce excessive reactive oxygen species formation, p53 expression, and most importantly, caspase-2 activation. After the activation of the caspase-2, the cells exhibited hallmarks of apoptotic pathway, such as mitochondrial damage and translocation of Bax and cytochrome c, which were then followed by caspase-3 activation. By pretreating the cells with a cell-permeable, biotinylated pan-caspase inhibitor, we identified caspase-2 as an initiator caspase in EtOH-treated corneal fibroblasts. Loss of caspase-2 inhibited EtOH-induced apoptosis. We further found that caspase-2 acts upstream of mitochondria to mediate EtOH-induced apoptosis. The loss of caspase-2 significantly inhibited EtOH-induced mitochondrial dysfunction, Bax translocation, and cytochrome c release from mitochondria. The pretreatment of CoQ10 prevented EtOH-induced caspase-2 activation and mitochondria-mediated apoptosis. Our data demonstrated that by blocking caspase-2 activity, CoQ10 can protect the cells from mitochondrial membrane change, apoptotic protein translocation, and apoptosis. Taken together, EtOH-induced mitochondria-mediated apoptosis is initiated by caspase-2 activation, which is regulated by CoQ10. PMID:23430247

  12. Detection of in vivo DNA damage induced by ethanol in multiple organs of pregnant mice using the alkaline single cell gel electrophoresis (Comet) assay.

    PubMed

    Kido, Ryoko; Sato, Itaru; Tsuda, Shuji

    2006-01-01

    Ethanol is principal ingredient of alcohol beverage, but considered as human carcinogen, and has neurotoxicity. Alcohol consumption during pregnancy often causes fetal alcohol syndrome. The DNA damage is one of the important factors in carcinogenicity or teratogenicity. To detect the DNA damage induced by ethanol, we used an in vivo alkaline single cell gel electrophoresis (Comet) assay in pregnant mice organs and embryos. Pregnant ICR mice on Day 7 of gestation were treated with 2, 4 or 8 g/kg ethanol, and maternal organs/tissues and embryos were subjected to the Comet assay at 4, 8, 12 and 24 hr after ethanol treatment. Four and 8 g/kg ethanol induced DNA damage in brain, lung and embryos at 4 or 8 hr after the treatment. Two g/kg ethanol did not cause any DNA damage, and 8 g/kg ethanol only increased the duration of DNA damage without distinct increase in the degree of the damage. No significant DNA damage was observed in the liver. To detect the effect of acetaldehyde, disulfiram, acetaldehyde dehydrogenase inhibitor, was administered before 4 g/kg ethanol treatment. No significant increase of DNA damage was observed in the disulfiram pre-treated group. These data indicate that ethanol induces DNA damage, which might be related to ethanol toxicity. Since pre-treatment of disulfiram did not increase DNA damage, DNA damage observed in this study might not be the effect of acetaldehyde. PMID:16462115

  13. Hepatic dysfunction.

    PubMed

    McCord, Kelly W; Webb, Craig B

    2011-07-01

    This article reviews the common pathophysiology that constitutes hepatic dysfunction, regardless of the inciting cause. The systemic consequences of liver failure and the impact of this condition on other organ systems are highlighted. The diagnostic tests available for determining the cause and extent of liver dysfunction are outlined, treatment strategies aimed at supporting hepatic health and recovery are discussed, and prognosis is briefly covered. The article emphasizes the fact that because of the central role of the liver in maintaining normal systemic homeostasis, hepatic dysfunction cannot be effectively addressed as an isolated entity. PMID:21757090

  14. Hepatic Encephalopathy

    PubMed Central

    Bleibel, Wissam; Al-Osaimi, Abdullah M. S.

    2012-01-01

    Chronic liver disease and cirrhosis affect hundreds of millions of patients all over the world. The majority of patients with cirrhosis will eventually develop complications related to portal hypertension. One of these recurrent and difficult to treat complications is hepatic encephalopathy. Studies have indicated that overt hepatic encephalopathy affects 30 to 45% of patients with cirrhosis and a higher percentage may be affected by minimal degree of encephalopathy. All of these factors add to the impact of hepatic encephalopathy on the healthcare system and presents a major challenge to the gastroenterologist, hospitalist and primary care physician. PMID:23006457

  15. Mechanisms of Gastroprotective Effects of Ethanolic Leaf Extract of Jasminum sambac against HCl/Ethanol-Induced Gastric Mucosal Injury in Rats

    PubMed Central

    AlRashdi, Ahmed S.; Salama, Suzy M.; Alkiyumi, Salim S.; Abdulla, Mahmood A.; Hadi, A. Hamid A.; Abdelwahab, Siddig I.; Taha, Manal M.; Hussiani, Jamal; Asykin, Nur

    2012-01-01

    Jasminum sambac is used in folk medicine as the treatment of many diseases. The aim of the present investigation is to evaluate the gastroprotective effects of ethanolic extracts of J. sambac leaves against acidified ethanol-induced gastric ulcers in rats. Seven groups of rats were orally pre-treated with carboxymethylcellulose (CMC) as normal group, CMC as ulcer group, 20?mg/kg of omeprazole as positive group, 62.5, 125, 250, and 500?mg/kg of extract as the experimental groups, respectively. An hour later, CMC was given orally to normal group and acidified ethanol solution was given orally to the ulcer control, positive control, and the experimental groups. The rats were sacrificed after an hour later. Acidity of gastric content, the gastric wall mucus, ulcer areas, and histology and immunohistochemistry of the gastric wall were assessed. Gastric homogenates were determined for prostaglandin E2 (PGE2), superoxide dismutase (SOD), andmalondialdehyde (MDA) content. Ulcer group exhibited significantly severe mucosal injury as compared with omeprazole or extract which shows significant protection towards gastric mucosal injury the plant promotes ulcer protection as it shows significant reduction of ulcer area grossly, and histology showed marked reduction of edema and leucocytes infiltration of submucosal layer compared with ulcer group. Immunohistochemistry showed overexpression of Hsp70 protein and downexpression of Bax protein in rats pretreated with extract. Significant increased in the pH, mucus of gastric content and high levels of PGE2, SOD and reduced amount of MDA was observed. PMID:22550543

  16. Protective effects of green tea against hepatic injury induced by high-cholesterol diet in rats: histopathological analysis, oxidative DNA damage and COX-2 expression.

    PubMed

    de Moraes, Bárbara B; Pasquini, Gabriela; Aguiar, Odair; Gollücke, Andréa P B; Ihara, Silvia S M; Tenorio, Neuli M; Andersen, Monica L; Catharino, Rodrigo R; Spadari-Bratfisch, Regina Celia; Ribeiro, Daniel Araki

    2011-06-21

    PURPOSE: The goal of this study was to investigate whether daily administration of green tea is able to protect the liver injury induced by cholesterol. METHODS: Male Wistar rats (n = 24) were distributed into four groups: group 1, negative control; group 2, cholesterol at 1% (w/w) in the diet treated for 5 weeks; group 3, cholesterol at 1% treated for 5 weeks and green tea at 1% (w/v) in drinking water in the last week only and group 4, cholesterol and green tea at 1% in drinking water for 5 weeks. RESULTS: The results pointed out that treatment with green tea in the last week (group 3) showed mild degenerative changes of liver tissue in cholesterol exposed group when compared to group 2. Green tea aqueous extract was not able to reduce cholesterol levels, that is, no significant statistical differences (p > 0.05) were noticed when compared to positive control group. Nevertheless, green tea was able to decrease oxidative deoxyribonucleic acid (DNA) damage either to peripheral blood or to liver cells as depicted by significant statistical differences (p < 0.05) in the mean tail moment between groups treated with green tea and cholesterol and cholesterol only. Furthermore, histomorphometric analysis of COX-2 expression revealed that in groups exposed to green tea they were significantly decreased (p < 0.05), regardless of time exposure adopted. CONCLUSION: Taken together, our results suggest that daily administration of green tea for at least 7 days displays some preventive properties as indicated by COX-2 downregulation and decreased oxidative DNA damage. PMID:21691717

  17. Hepatic manifestations of metabolic syndrome.

    PubMed

    Medina-Santillán, Roberto; López-Velázquez, Jorge A; Chávez-Tapia, Norberto; Torres-Villalobos, Gonzalo; Uribe, Misael; Méndez-Sánchez, Nahum

    2013-03-01

    The prevalence of metabolic syndrome is growing around the world at an alarming rate. Obesity involves a plethora of molecules that predispose individuals to an inflammatory state and various metabolic complications. Dysregulation of nutrient metabolism is a key step during the progression of chronic liver disease that induces an inflammatory state, cellular damage, and impaired hepatic insulin signaling, which leads to insulin resistance. Insulin resistance arises from multiple defects in the liver, adipose tissues, and muscle signaling, which leads to a failure to suppress hepatic gluconeogenesis and glycogenolysis, thereby enhancing fat accumulation in the hepatocytes via increased lipolysis and increased hepatic synthesis of triglycerides. This metabolic condition also increases the frequency of other comorbidities such as liver and biliary diseases. Nonalcoholic fatty liver disease is the hepatic expression of metabolic syndrome, which comprises a spectrum of clinical and histological events ranging from simple and benign fatty liver to steatohepatitis, which is characterized by the abnormal activation of pathways leading to an aggressive inflammatory condition. This pathological state may progress to more severe damage known as cirrhosis, which endangers the anatomy and function of liver tissue. In addition, a small group of patients with end-stage liver disease may develop hepatocellular carcinoma and finally death. By contrast, cholesterol gallstone disease is a common metabolic disease, and is considered to be the main biliary indicator of metabolic syndrome. This review provides a detailed summary of the hepatic manifestations associated with metabolic syndrome. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23471889

  18. Hepatitis A

    MedlinePLUS

    ... Less commonly, viral infections such as mononucleosis or cytomegalovirus can cause hepatitis. There are 2 main kinds ... urine Loss of appetite Muscle pain Itching Young children are likely to have very mild cases of ...

  19. Hepatic Encephalopathy

    MedlinePLUS Videos and Cool Tools

    ... is a condition that causes temporary worsening of brain function in people with advanced liver disease. When ... travel through your body until they reach your brain, causing mental and physical symptoms of HE. Hepatic ...

  20. Hepatitis A.

    PubMed

    Matheny, Samuel C; Kingery, Joe E

    2012-12-01

    Hepatitis A is a common viral illness worldwide, although the incidence in the United States has diminished in recent years as a result of extended immunization practices. Hepatitis A virus is transmitted through fecal-oral contamination, and there are occasional outbreaks through food sources. Young children are usually asymptomatic, although the likelihood of symptoms tends to increase with age. Most patients recover within two months of infection, although 10 to 15 percent of patients will experience a relapse in the first six months. Hepatitis A virus does not usually result in chronic infection or chronic liver disease. Supportive care is the mainstay of treatment. The Centers for Disease Control and Prevention and the American Academy of Pediatrics recommend routine vaccination of all children 12 to 23 months of age, as well as certain vulnerable populations. Hepatitis A vaccine is also recommended for most cases of postexposure prophylaxis, although immunoglobulin is an acceptable alternative in some situations. PMID:23198670

  1. Autoimmune hepatitis

    Microsoft Academic Search

    Diego Vergani; Maria Serena Longhi; Dimitrios P. Bogdanos; Yun Ma; Giorgina Mieli-Vergani

    2009-01-01

    Autoimmune hepatitis (AIH) is an inflammatory liver disease affecting mainly females and characterised histologically by interface\\u000a hepatitis, biochemically by elevated transaminase levels and serologically by the presence of autoantibodies and increased\\u000a levels of immunoglobulin G. AIH responds to immunosuppressive treatment, which should be instituted as soon as diagnosis is\\u000a made. Seropositivity for smooth muscle and\\/or anti-nuclear antibody defines type 1

  2. Ticlopidine prevents the formation but delays the healing of ethanol-induced gastric lesions in the rat.

    PubMed

    Sibilia, V; Pagani, F; Lattuada, N; De Luca, V; Guidobono, F; Soglian, A; Netti, C

    2007-05-01

    The effects of acute or long-term oral ticlopidine administration in normal rat gastric mucosa or on gastric lesions induced by ethanol 50% (EtOH, 1 ml/rat, os) were examined and compared with those of acetylsalicylic acid (ASA). Ticlopidine does not affect gastric mucosal integrity either after acute (100 and 300 mg kg(-1)) or 1-week (100 mg kg(-1), die) oral administration. Ticlopidine (30-300 mg kg(-1), os) administered 1h before EtOH dose-dependently prevented the development of gastric haemorragic lesions. When ticlopidine was administered 1h after EtOH, it significantly (p<0.05) delays gastric lesions healing. Acute ASA (50 and 100 mg kg(-1), os) administration causes a mild irritant activity similar to that observed after 1 week of ASA (50 mg kg(-1), os/die) administration. In condition of mucosal damage, ASA does not modify either the induction or the healing of EtOH-induced gastric lesions. To assess the possible involvement of endogenous nitric oxide (NO) or prostaglandins (PG) in the gastric protective activity of ticlopidine, the rats were pretreated with an inhibitor of NO-synthesis, L-NAME (70 mg kg(-1), s.c.) or the inhibitor of PG synthesis, indomethacin (Indo, 10 mg kg(-1), s.c.). Indo, but not L-NAME, was able to significantly counteract the gastroprotective activity of ticlopidine against EtOH injury. Furthermore, ticlopidine increases (47%) gastric PGE(2) content in normal mucosa compared to the one detected in control rats, thus suggesting that endogenous PGs contribute to enhanced mucosal resistance by ticlopidine. These results indicate that ticlopidine exerts dual effects during the development and healing of gastric lesions induced by EtOH. PMID:17324584

  3. Feature Hepatitis: Hepatitis Symptoms, Diagnosis, Treatment & Prevention

    MedlinePLUS

    ... Navigation Bar Home Current Issue Past Issues Feature Hepatitis Hepatitis: Symptoms, Diagnosis, Treatment & Prevention Past Issues / Spring 2009 ... No appetite Fever Headaches Diagnosis To check for hepatitis viruses, your doctor will test your blood. You ...

  4. Hepatic-Specific Lipin-1 Deficiency Exacerbates Experimental Alcohol-Induced Steatohepatitis in Mice

    PubMed Central

    Hu, Ming; Yin, Huquan; Mitra, Mayurranjan S.; Liang, Xiaomei; Ajmo, Joanne M.; Nadra, Karim; Chrast, Roman; Finck, Brian N.; You, Min

    2013-01-01

    Lipin-1 regulates lipid metabolism via its function as an enzyme in the triglyceride synthesis pathway and as a transcriptional co-regulatory protein and is highly up-regulated in alcoholic fatty liver disease. In the present study, using a liver specific lipin-1-deficient (lipin-1LKO) mouse model, we aimed to investigate the functional role of lipin-1 in the development of alcoholic steatohepatitis and explore the underlying mechanisms. Alcoholic liver injury was achieved by pair feeding wild-type (WT) and lipin-1LKO mice with modified Lieber-DeCarli ethanol-containing low fat diets for 4-wks. Surprisingly, chronically ethanol-fed lipin-1LKO mice showed markedly greater hepatic triglyceride and cholesterol accumulation, and augmented elevation of serum liver enzymes accompanied by increased hepatic pro-inflammatory cytokine expression. Our studies further revealed that hepatic removal of lipin-1 in mice augmented ethanol-induced impairment of hepatic fatty acid oxidation and lipoprotein production likely via deactivation of PGC-1?, a prominent transcriptional regulator of lipid metabolism. Our findings demonstrate that liver-specific lipin-1 deficiency in mice exacerbates the development and progression of experimental alcohol-induced steatohepatitis. Pharmacological or nutritional modulation of hepatic lipin-1 may be beneficial for the prevention or treatment of human alcoholic fatty liver disease. PMID:23787969

  5. Temporal effects of ethanol consumption on energy homeostasis, hepatic steatosis and insulin sensitivity in mice

    PubMed Central

    Carr, Rotonya M.; Dhir, Ravi; Yin, Xiaoyan; Agarwal, Beamon; Ahima, Rexford S.

    2013-01-01

    Background Alcoholic liver disease progresses from steatosis to inflammation, fibrosis and cirrhosis. Although alcoholic liver disease has been associated with insulin resistance, it is unclear whether insulin resistance coincides with the development of steatosis. Methods We studied the temporal relationship of steatosis and glucose homeostasis in mice fed a Lieber-DeCarli liquid control or ethanol diet for 2, 4 or 8 weeks. We studied the effects of alcohol consumption on energy balance, body composition, and hepatic lipids. Glucose tolerance test was performed, and insulin sensitivity was evaluated with hyperinsulinemic-euglycemic clamp. Results Ethanol-fed mice developed hepatic steatosis over time as compared with control-fed mice despite similar energy intake and expenditure, and gain in body weight and fat. Ethanol-fed mice developed glucose intolerance as early as 2 weeks, while insulin resistance developed at 4 weeks. A hyperinsulinemic-clamp study at 8 weeks revealed both hepatic and peripheral insulin resistance in ethanol-fed mice. Insulin resistance was associated with hepatic steatosis, increased ceramide levels, and Perilipin 2 expression. Conclusions Chronic ethanol consumption leads to the development of hepatic steatosis, impaired glucose tolerance and insulin resistance. These changes are independent of energy intake or expenditure, weight, whole body fat content, and inflammation. A better understanding of the processes linking ethanol-induced steatosis and abnormal glucose homeostasis may lead to novel therapies targeting the progression of alcoholic liver disease. PMID:23398239

  6. Protective effects of melittin on tumor necrosis factor-? induced hepatic damage through suppression of apoptotic pathway and nuclear factor-kappa B activation.

    PubMed

    Park, Ji-Hyun; Lee, Woo-Ram; Kim, Hyun-Soo; Han, Sang-Mi; Chang, Young-Chae; Park, Kwan-Kyu

    2014-12-01

    Melittin, a major polypeptide in honeybee venom, have been used to treat inflammatory disease. Various studies have demonstrated the anti-bacterial, anti-viral, anti-inflammatory and anticancer effects of bee venom and melittin. However, the precise mechanism of melittin in liver disease is not yet known. Apoptosis contributes to liver inflammation and fibrosis. Knowledge of the apoptotic mechanisms is important to develop new and effective therapies for treatment of cirrhosis. In the present study, we investigated the anti-apoptotic effect of melittin on tumor necrosis factor (TNF)-?/actinomycin (Act) D-induced apoptosis in hepatocytes. Our results show significant protection from DNA damage by melittin treatment compared with corresponding TNF-?/Act D-treated hepatocytes without melittin. Melittin inhibited TNF-?/Act D-induced activation of the caspase, bcl-2 family of proteins and poly ADP-ribose polymerase (PARP)-1. Our results also indicate that melittin decreased nuclear factor-kappa B (NF-?B) by degradation of phosphorylation of I?B kinase (p-IKK) and NF-?B DNA binding activity in TNF-?/Act D-treated hepatocytes. These results suggest that melittin possesses a potent suppressive effect on apoptotic responses in TNF-?/Act D-treated hepatocytes via the NF-?B pathway. PMID:24872433

  7. [Chronic hepatitis].

    PubMed

    Figueroa Barrios, R

    1995-01-01

    Medical literature about chronic hepatitis is reviewed. This unresolving disease caused by viruses, drugs or unknown factors may progress to in cirrhosis and hepatocarcinoma. A classification based on liver biopsy histology into chronic persistent and chronic active types has been largely abandoned and emphasis is placed on recognizing the etiology of the various types. One is associated with continuing hepatitis B virus infection; another is related to chronic hepatitis C virus infection and the third is termed autoinmune, because of the association with positive serum autoantibodies. A fourth type with similar clinical functional and morphologic features is found with some drug reactions. Long term corticoesteroid therapy is usually successful in autoinmune type. Associations between antibodies to liver-kidney microsomes and the hepatitis C virus can cause diagnostic difficulties. Antiviral treatment of chronic hepatitis B and C with interpheron alfa is employed, controlling symptoms and abnormal biochemistry and the progression to cirrhosis and liver cancer in 30 to 40% patients. Alternative therapies or combinations with interpheron are being evaluated waiting for final results. PMID:8520023

  8. Cerebroprotective effect of isolated harmine alkaloids extracts of seeds of Peganum harmala L. on sodium nitrite-induced hypoxia and ethanol-induced neurodegeneration in young mice.

    PubMed

    Biradar, S M; Joshi, Hanumanthachar; Tarak, K C

    2013-12-01

    The aim of the study was to isolate the harmine alkaloids from the seeds of Peganum harmala (TAPH) and its cerebroprotective effect on cognitive deficit mice. The tested doses of TAPH were screened for Sodium nitrite induced hypoxia and Ethanol induced neurodegeneration using behavioral models. The TAPH was found to be non-neurotoxic and Psychoactive by preventing the motor impairment and increasing the locomotion activity of animals in Rota rod and Actophotometer respectively. TAPH (5, 2.5 and 1.25 mg kg(-1) p.o.) significantly (p < 0.001) protected the Sodium nitrite induced memory impairment by decreasing the time require to find the water bottle in special water bottle case model. In Elevated Plus Maze (EPM) and Passive Shock Avoidance paradigm (PSA) the TAPH shown improved acquisition and retention memory significantly (p < 0.001) by decreasing the Transverse Latency Time (TLT) and increasing the Step Down Latency (SDL), respectively in dose dependent manner. The results were well supported by biochemical parameters, by inhibiting the Acetylcholinestrase (p < 0.01) activity, increasing the GSH (p < 0.001) level and decreasing the TBARS (p < 0.001) level of whole brain. Moreover TAPH has shown the significant Monoamine oxidase-A (MAO-A) inhibition action (p < 0.001), hence it reduces the metabolism of epinephrine, 5-HT and other monoamines and enhances the action of these neurotransmitters indirectly; this adrenergic system plays an important role in learning and memory. Further, TAPH (5 mg kg(-1)) protect the DNA fragmentation of frontotemporal cortex of the brain from hypoxic effect induced by Sodium nitrite in Gel Electrophoresis studies. The results were comparable to their respective standards. Hence, harmine alkaloids are potential enough to utilize in the management of Neurodegenerative disorders of the type Alzheimer's diseases. PMID:24506035

  9. Differences in sensitivity to ethanol-induced conditioned taste aversions emerge after pre- or post-pubertal gonadectomy in male and female rats

    PubMed Central

    Morales, Melissa; Spear, Linda P.

    2012-01-01

    We have previously demonstrated that gonadectomy either prior to (early) or after (late) puberty elevated ethanol consumption in males to levels similar to intact adult females—effects that were attenuated by testosterone replacement. To assess whether alterations in the aversive effects of ethanol might contribute to gonadectomy-associated increases in ethanol intake in males, the present study examined the impact of gonadectomy on conditioned taste aversions (CTA) to ethanol in male and female Sprague-Dawley rats. Animals were gonadectomized, received sham surgery (SH) or non-manipulated (NM) on postnatal (P) day 23 (early) or 67 (late) and tested for CTA to ethanol in adulthood. Water-deprived rats were given 1 hr access every-other-day to 10% sucrose followed by an injection of ethanol (0, 1 g/kg) for 5 test sessions. Test data were analyzed to determine the first day significant aversions emerged in each ethanol group (i.e., sucrose intakes significantly less than their saline-injected counterparts). Early gonadectomized males acquired the CTA more rapidly than did early SH and NM males (day 1 vs 3 and 4 respectively), whereas a gonadectomy-associated enhancement in ethanol CTA was not evident in late males. Among females, gonadectomy had little impact on ethanol-induced CTA, with females in all groups showing an aversion by the first or second day, regardless of surgery age. These data suggest that previously observed elevations in ethanol intake induced by either pre- or post-pubertal gonadectomy in males are not related simply to gonadectomy-induced alterations in the aversive effects of ethanol indexed via CTA. PMID:23195111

  10. Acute Toxicity and Gastroprotection Studies of a New Schiff Base Derived Copper (II) Complex against Ethanol-Induced Acute Gastric Lesions in Rats

    PubMed Central

    Hassandarvish, Pouya; Gwaram, Nura Suleiman; A. Hadi, A. Hamid; Mohd Ali, Hapipah; Majid, Nazia; Abdulla, Mahmood Ameen

    2012-01-01

    Background Copper is an essential element in various metabolisms. The investigation was carried out to evaluate acute gastroprotective effects of the Copper (II) complex against ethanol-induced superficial hemorrhagic mucosal lesions in rats. Methodology/Principal Findings Rats were divided into 7 groups. Groups 1 and 2 were orally administered with Tween 20 (10% v/v). Group 3 was orally administered with 20 mg/kg omeprazole (10% Tween 20). Groups 4–7 received 10, 20, 40, and 80 mg/kg of the complex (10% Tween 20), respectively. Tween 20 (10% v/v) was given orally to group 1 and absolute ethanol was given orally to groups 2–7, respectively. Rats were sacrificed after 1 h. Group 2 exhibited severe superficial hemorrhagic mucosal lesions. Gastric wall mucus was significantly preserved by the pre-treatment complex. The results showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE2) activities and a decrease in malondialdehyde (MDA) level. Histology showed marked reduction of hemorrhagic mucosal lesions in groups 4–7. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. PAS staining of groups 4–7 showed intense stain uptake of gastric mucosa. The acute toxicity revealed the non-toxic nature of the compound. Conclusions/Significance The gastroprotective effect of the Copper (II) complex may possibly be due to preservation of gastric wall mucus; increase in PGE2 synthesis; GSH, SOD, and NO up-regulation of Hsp70 protein; decrease in MDA level; and down-regulation of Bax protein. PMID:23251568

  11. Activation and role of the medial prefrontal cortex (mPFC) in extinction of ethanol-induced associative learning in mice

    PubMed Central

    Groblewski, Peter A.; Ryabinin, Andrey E.; Cunningham, Christopher L.

    2011-01-01

    Although the medial prefrontal cortex (mPFC) has been shown to be integrally involved in extinction of a number of associative behaviors, its role in extinction of alcohol (ethanol)-induced associative learning has received little attention. Previous reports have provided evidence supporting a role for the mPFC in acquisition and extinction of amphetamine-induced conditioned place preference (CPP) in rats, however, it remains unknown if this region is necessary for extinction of ethanol (EtOH)-induced associative learning in mice. Using immunohistochemical analysis of phosphorylated and unphosphorylated cAMP response element-binding protein (CREB), the current set of experiments first showed that the prelimbic (PL) and infralimbic (IL) subregions of the mPFC exhibited dynamic responses in phosphorylation of CREB to a Pavlovian-conditioned, EtOH-paired cue. Interestingly, CREB phosphorylation within these regions was sensitive to manipulations of the EtOH-cue contingency—that is, the cue-induced increase of pCREB in both the PL and IL was absent following extinction. In order to confirm a functional role of the mPFC in regulating the extinction process, we then showed that electrolytic lesions of the mPFC following acquisition blocked subsequent extinction of EtOH-CPP. Together, these experiments indicate a role for the PL and IL subregions of the mPFC in processing changes of the EtOH-cue contingency, as well as in regulating extinction of EtOH-induced associative learning in mice. PMID:21951632

  12. Cytotoxic and DNA-damaging effects of diterpenoid quinones from the roots of Salvia officinalis L. on colonic and hepatic human cells cultured in vitro.

    PubMed

    Slamenová, Darina; Masterová, Irena; Lábaj, Juraj; Horváthová, Eva; Kubala, Pavol; Jakubíková, Jana; Wsólová, Ladislava

    2004-06-01

    Three diterpenoid quinones (royleanone- SAR 3, horminone- SAR 26, and acetyl horminone- SAR 43) isolated from the roots of Salvia officinalis L. were tested for their cytotoxic and DNA-damaging activity in human colon carcinoma cells Caco-2 and human hepatoma cells HepG2 cultured in vitro. Cytotoxicity was measured by the trypan blue exclusion technique and induction of apoptosis was evaluated by flow immunofluorocytometry after 30-300 min. exposure of HepG2 and Caco-2 cells to diterpenoid quinones and following 24 hr post-incubation in the culture medium. Induction of DNA breaks was measured after 60 min. exposure of cells to different concentrations of the compounds studied by the alkaline elution of DNA and by the Comet assay. Though all the quinones tested decreased the viability of the cells studied proportionally to the concentration and to the time of treatment (cytotoxicity= 30-60%), the increased level of apoptotic nuclei comparable to the level of apoptotic nuclei induced by a topoisomerase I inhibitor was proved only in HepG2 cells treated with 1x10(-4) mol/l SAR 26 or SAR 43. Either no or marginal increase of the level of apoptotic nuclei was observed in SAR 3-treated HepG2 cells and in SAR 3-, SAR 26- or SAR 43-treated Caco-2 cells. All compounds tested induced creation of DNA strand breaks in both cell types at concentrations >1x10(-7)-1x10(-6) mol/l. The occurrence of DNA strand breaks at different pH values as well as the kinetics of DNA breaks rejoining were evaluated only in colonic cells Caco-2. The Comet assay processed in parallel at pH 13.0 and pH 12.1 showed that strand breaks detected in SARs-treated colonic Caco-2 cells originated from alkali-labile sites, as induced DNA lesions were converted to DNA strand breaks only under strong alkaline conditions. The kinetics of DNA rejoining revealed that SARs-induced DNA breaks were repaired very slowly. PMID:15228500

  13. Mistletoe hepatitis.

    PubMed Central

    Harvey, J; Colin-Jones, D G

    1981-01-01

    A 49-year-old woman presented with nausea, general malaise, and a dull ache in the right hypochondrium. Liver biopsy showed slight inflammatory-cell infiltration, and results of liver function tests suggested hepatitis. Hepatitis B surface antigen was not detected, and a cholecystogram was normal. Two years later she presented with similar symptoms, and both illnesses were found to have occurred after ingestion of a herbal remedy containing kelp, motherwort, skullcap, and mistletoe. A challenge test established this to be the cause of the illness. Mistletoe is the only constituent of the tablets known to contain any potential toxin and thus was probably the cause of the illness. Mistletoe is widely used in herbal remedies, whose ingestion may therefore cause hepatitis. Images FIG 1 FIG 2 PMID:6779941

  14. Hepatitis C

    NSDL National Science Digital Library

    Patient Education Institute

    This patient education program explains Hepatitis C, the liver and Hepatitis, symptoms, diagnosis, treatment, risk factors, and prevention. This is a MedlinePlus Interactive Health Tutorial from the National Library of Medicine, designed and developed by the Patient Education Institute. NOTE: The tutorial requires a special Flash plug-in, version 4 or above. If you do not have Flash, you will be prompted to obtain a free download of the software before you start the tutorial. You will also need an Acrobat Reader, available as a free download, in order to view the Reference Summary.

  15. Hepatic angiomyolipoma.

    PubMed

    Pounder, D J

    1982-10-01

    An angiomyolipoma of the liver was an incidental autopsy finding in a 65-year-old man. This is the third recorded primary hepatic angiomyolipoma. There were no stigmata of tuberose sclerosis but tuberose sclerosis has been reported previously in association with fatty tumors of the liver, suggesting that such lesions, like their renal counterparts, may be choristomas. PMID:7180967

  16. Autoimmune Hepatitis

    MedlinePLUS

    ... hepatitis is the most common form in North America. Type 1 can occur at any age; however, ... transplant in a hospital. When possible, the patient fasts for 8 hours before the ... medications, contact the U.S. Food and Drug Administration toll-free at 1–888– ...

  17. Hepatitis C

    MedlinePLUS

    ... items such as razors and toothbrushes. Practice safer sex . If you or your partner is infected with hepatitis C and you have been in a stable and monogamous (no other partners) relationship, the risk of giving the virus to, or getting ...

  18. Hepatitis B

    MedlinePLUS

    ... liver failure, or liver cancer. There is a vaccine for HBV. It requires three shots. All babies should get ... it too. If you travel to countries where Hepatitis B is common, you should get the vaccine. NIH: National Institute of Diabetes and Digestive and ...

  19. Hepatitis B

    MedlinePLUS

    ... B to come back? Should I get the hepatitis B vaccine? What are the side effects of antiviral medicines? Will my liver ever be normal again? Written by familydoctor.org editorial staff Reviewed/Updated: 03/14 Created: 10/96

  20. Hepatitis and Asian Americans

    MedlinePLUS

    ... from hepatitis C than non-Hispanic whites. VIRAL HEPATITIS Death Rates for Viral Hepatitis, 2013 (all types) ... data/nvsr/nvsr64/nvsr64_02.pdf [PDF | 2MB] HEPATITIS A Hepatitis A, Acute (Cases per 100,000 ...

  1. Delta agent (Hepatitis D)

    MedlinePLUS

    ... is found only in people who carry the hepatitis B virus. HDV may make liver disease worse in people ... can even cause symptoms in people who carry hepatitis B virus but who never had symptoms. Hepatitis D infects ...

  2. Alcoholic hepatitis

    Microsoft Academic Search

    Kester I. Crosse; Frank A. Anania

    2002-01-01

    Opinion statement  Alcoholic hepatitis is a common clinical problem confronting gastroenterologists and hepatologists alike. The fundamental\\u000a issue regarding treatment of this disease is its recognition on the part of the physician. Chronic alcohol abuse, fever, leukocytosis,\\u000a jaundice, and encephalopathy are key symptoms and signs that should prompt consideration of this diagnosis. Nutrition and\\u000a abstinence from alcohol are the cornerstones of therapy.

  3. Hepatitis E.

    PubMed

    Aggarwal, Rakesh; Jameel, Shahid

    2011-12-01

    Hepatitis E refers to liver disease caused by the hepatitis E virus (HEV), a small, nonenveloped virus with a single-stranded RNA genome. The virus has four genotypes, but only one serotype. Genotypes 1 and 2 exclusively infect humans, whereas genotypes 3 and 4 also infect pigs and several other mammalian species. Though HEV does not grow well in cell culture, several aspects of its biology and pathogenesis have been worked out using animal models and cell transfection studies, and by analogy with other related viruses. HEV itself appears noncytopathic, and the liver injury during hepatitis E may be mediated by the host immune response. In areas with poor sanitation, HEV infection is common and presents as outbreaks and also as sporadic cases with acute self-limited hepatitis. The transmission is feco-oral, usually through contaminated drinking water. The disease often affects young adults and is particularly severe among pregnant women and persons with preexisting liver cirrhosis. In the developed world, the disease is being increasingly recognized. It occurs as occasional sporadic cases, most often among elderly men with coexisting illnesses. These appear to be related to zoonotic transmission. Chronic infection is known among immunosuppressed persons in these regions and may progress to liver cirrhosis. Serological tests for diagnosis of HEV exposure and recent infection, namely immunoglobulin (Ig)G and IgM anti-HEV, respectively, need further improvement in sensitivity and specificity, particularly when used in developed countries. Two recombinant protein vaccines have undergone successful human trials, but are not yet commercially available. Recent development of cell-culture methods for HEV should allow a better understanding of this enigmatic agent. PMID:21932388

  4. Autoimmune hepatitis.

    PubMed

    Sahebjam, Farhad; Vierling, John M

    2015-06-01

    Autoimmune hepatitis is a chronic liver disease putatively caused by loss of tolerance to hepatocytespecific autoantigens. It is characterized by female predilection, elevated aminotransferase levels, autoantibodies, increased ?-globulin or IgG levels and biopsy evidence of interface hepatitis. It is currently divided into types 1 and 2, based on expression of autoantibodies. Autoantigenic epitopes have been identified only for the less frequent type 2. Although autoimmune hepatitis occurs in childhood, this review focuses on disease in adults. In the absence of pathognomonic biomarkers, diagnosis requires consideration of clinical, biochemical, serological and histological features, which have been codified into validated diagnostic scoring systems. Since many features also occur in other chronic liver diseases, these scoring systems aid evaluation of the differential diagnosis. New practice guidelines have redefined criteria for remission to include complete biochemical and histological normalization on immunosuppressive therapy. Immunosuppression is most often successful using prednisone or prednisolone and azathioprine; however, the combination of budesonide and azathioprine for non-cirrhotic patients offers distinct advantages. Patients failing standard immunosuppression are candidates for alternative immunosuppressive regimens, yet none of the options has been studied in a randomized, controlled trial. Overlap syndromes with either primary sclerosing cholangitis or primary biliary cirrhosis occur in a minority. Liver transplantation represents a life-saving option for patients presenting with acute liver failure, severely decompensated cirrhosis or hepatocellular carcinoma. Transplant recipients are at risk for recurrent autoimmune hepatitis in the allograft, and de novo disease may occur in patients transplanted for other indications. Patients transplanted for AIH are also at risk for recurrent or de novo inflammatory bowel disease. Progress in our understanding of the immunopathogenesis should lead to identification of specific diagnostic and prognostic biomarkers and new therapeutic strategies. PMID:25749982

  5. Lesions of the Lateral Habenula Increase Voluntary Ethanol Consumption and Operant Self-Administration, Block Yohimbine-Induced Reinstatement of Ethanol Seeking, and Attenuate Ethanol-Induced Conditioned Taste Aversion

    PubMed Central

    Schwager, Andrea L.; Sinclair, Michael S.; Tandon, Shashank; Taha, Sharif A.

    2014-01-01

    The lateral habenula (LHb) plays an important role in learning driven by negative outcomes. Many drugs of abuse, including ethanol, have dose-dependent aversive effects that act to limit intake of the drug. However, the role of the LHb in regulating ethanol intake is unknown. In the present study, we compared voluntary ethanol consumption and self-administration, yohimbine-induced reinstatement of ethanol seeking, and ethanol-induced conditioned taste aversion in rats with sham or LHb lesions. In rats given home cage access to 20% ethanol in an intermittent access two bottle choice paradigm, lesioned animals escalated their voluntary ethanol consumption more rapidly than sham-lesioned control animals and maintained higher stable rates of voluntary ethanol intake. Similarly, lesioned animals exhibited higher rates of responding for ethanol in operant self-administration sessions. In addition, LHb lesion blocked yohimbine-induced reinstatement of ethanol seeking after extinction. Finally, LHb lesion significantly attenuated an ethanol-induced conditioned taste aversion. Our results demonstrate an important role for the LHb in multiple facets of ethanol-directed behavior, and further suggest that the LHb may contribute to ethanol-directed behaviors by mediating learning driven by the aversive effects of the drug. PMID:24695107

  6. Changes in hepatitis B virus DNA polymerase in relation to the outcome of acute hepatitis type B.

    PubMed Central

    Alberti, A; Diana, S; Eddleston, A L; Williams, R

    1979-01-01

    Serum levels of hepatitis B virus specific DNA polymerase and hepatitis B e antigen were studied serially in 34 patients with hepatitis B virus infection--20 who had the acute illness and recovered, seven who died with fulminant disease, three who died as a result of subacute hepatic necrosis, and four who went on to develop chronic active hepatitis. DNA polymerase activity was present in 16 (80%) and HBeAg in 13 (65%) of the uncomplicated cases at presentation and in all of those patients from whom the initial sample was obtained before the peak in aminotransferase. Both markers disappeared after 30 days from the onset but DNAP remained persistently positive during a follow-up period of four to 10 months in the four patients who progressed to chronic hepatitis. These results indicate that DNAP and HBeAg are transiently present in all cases of acute hepatitis B. Only their persistence after the acute episode could represent a useful prognostic marker of chronically. In this respect, DNAP was more reliable in our patients than HBeAg. In uncomplicated acute hepatitis, the peak in DNAP levels, which defines the time of maximum virus replication in the liver, preceded the peak in aminotransferase levels. Among the 10 patients who developed massive liver damage after hepatitis B infection, DNAP was detected in five of the seven with fluminant hepatitis, with enzyme levels that were comparable with those observed in uncomplicated acute hepatitis and presentation, but not in the cases of subacute hepatic necrosis. These findings are consistent with the hypothesis that in hepatitis B infection, liver damage, whatever the severity, is not directly related to the degree of virus replication. PMID:437551

  7. Oxidative stress in viral and alcoholic hepatitis

    Microsoft Academic Search

    Carmela Loguercio; Alessandro Federico

    2003-01-01

    Liver damage ranges from acute hepatitis to hepatocellular carcinoma, through apoptosis, necrosis, inflammation, immune response, fibrosis, ischemia, altered gene expression and regeneration, all processes that involve hepatocyte, Kupffer, stellate, and endothelial cells. Reactive oxygen and nitrogen species (ROS, RNS) play a crucial role in the induction and in the progression of liver disease, independently from its etiology. They are involved

  8. Hepatic arterial perfusion is essential for the spontaneous recovery from focal hepatic venous outflow obstruction in rats.

    PubMed

    Huang, H; Deng, M; Jin, H; Liu, A; Dirsch, O; Dahmen, U

    2011-11-01

    We previously observed that focal hepatic venous outflow obstruction recovered spontaneously by the formation of sinusoidal canals in a rat model of portal hyperperfusion. We aimed to investigate whether the lack of hepatic arterial perfusion aggravates parenchymal damage, decelerates recovery and influences the formation of sinusoidal canals after focal hepatic venous outflow obstruction. Rats were subjected to arterialized versus nonarterialized syngeneic liver transplantation after ligating the right median hepatic vein in the donor. Hepatic damage, microcirculation, regeneration and vascular remodeling were evaluated. In arterialized-recipients, confluent necrosis interspersed with viable periportal islands of hepatocytes, and vascularized sinusoidal canals with visible blood flow, surrounded by normal sinusoidal structure, were visible on postoperative day (POD) 2. Complete parenchymal recovery was consequently established by resorption of necrosis and hepatocyte proliferation, detected in viable portal islands and border zone. Lack of hepatic arterial perfusion caused complete necrosis in the obstruction zone without viable hepatocytes in the periportal area on POD2. Hepatocyte proliferation was only visible in the border zone. On POD28, perfused vascular structures, without neighboring normal sinusoidal structures, were observed in the scar-like area. Hepatic arterial perfusion determined the extent of hepatic necrosis, the formation of vascularized sinusoidal canals and the parenchymal recovery, after focal hepatic venous outflow obstruction. PMID:21831159

  9. Hepatic osteodystrophy.

    PubMed

    Gatta, Angelo; Verardo, Alberto; Di Pascoli, Marco; Giannini, Sandro; Bolognesi, Massimo

    2014-09-01

    Metabolic disturbances of bone are frequent in patients with chronic liver disease. The prevalence of osteoporosis among patients with advanced chronic liver disease is reported between 12% and 55%; it is higher in primary biliary cirrhosis. All patients with advanced liver disease should be screened for osteoporosis with a densitometry, especially if the etiology is cholestatic and in the presence of other risk factors. Clinical relevance of hepatic osteodystrophy increases after liver transplantation. After liver transplant, a rapid loss of bone mineral density can be detected in the first 6 months, followed by stabilization and slight improvement of the values. At the time of transplantation, bone density values are very important prognostic factors. Therapy of hepatic osteodystrophy is based primarily on the control of risk factors: cessation of tobacco and alcohol assumption, reduction of caffeine ingestion, exercise, supplementation of calcium and vitamin D, limitation of drugs such as loop diuretics, corticosteroids, cholestyramine. Bisphosphonates have been proposed for the therapy of osteoporosis in patients with liver disease, particularly after liver transplantation. The possible side effects of oral administration of bisphosphonates, such as the occurrence of esophageal ulcerations, are of particular concern in patients with liver cirrhosis and portal hypertension, due to the risk of gastrointestinal hemorrhage from ruptured esophageal varices, although this risk is probably overestimated. PMID:25568651

  10. Hepatitis B: Information for Parents

    MedlinePLUS

    ... protect against hepatitis B is by getting the hepatitis B vaccine. Doctors recommend that all children get the vaccine. ... child) Is the hepatitis B shot safe? The hepatitis B vaccine is very safe, and it is effective at ...

  11. Hepatitis Information for the Public

    MedlinePLUS

    ... of Viral Hepatitis Contact Us Quick Links to Hepatitis ... A | B | C | D | E Viral Hepatitis Home ... Outbreaks State and Local Partners & Grantees Resource Center Hepatitis Information for the Public Recommend on Facebook Tweet ...

  12. Ethanol-Induced Expression of ET-1 and ET-BR in Liver Sinusoidal Endothelial Cells and Human Endothelial Cells Involves Hypoxia-Inducible Factor-1? and MicroRNA-1991

    PubMed Central

    Yeligar, Samantha; Tsukamoto, Hidekazu; Kalra, Vijay K.

    2013-01-01

    Chronic alcohol consumption leads to inflammation and cirrhosis of the liver. In this study, we observed that liver sinusoidal endothelial cells (LSEC) derived from ethanol-fed rats showed several fold increases in the mRNA expression of endothelin-1 (ET-1), hypoxia-inducible factor-1? (HIF-1?), and inflammatory cytochemokines compared with control rat LSEC. We also observed the same results in acute ethanol-treated LSEC from control rats and human dermal microvascular endothelial cells. Ethanol-mediated ET-1 expression involved NADPH oxidase and HIF-1? activation. Furthermore, ethanol increased the expression of the ET-1 cognate receptor ET-BR in Kupffer cells and THP-1 monocytic cells, which also involved HIF-1? activation. Promoter analysis and chromatin immunoprecipitation showed that hypoxia response element sites in the proximal promoter of ET-1 and ET-BR were required for the binding of HIF-1? to up-regulate their expression. We showed that microRNAs, miR-199 among several microRNAs, attenuated HIF-1? and ET-1 expression, while anti-miR-199 reversed the effects, suggesting that ethanol-induced miR-199 down-regulation may contribute to augmented HIF-1? and ET-1 expression. Our studies, for the first time to our knowledge, show that ethanol-mediated ET-1 and ET-BR expression involve HIF-1?, independent of hypoxia. Additionally, ethanol-induced ET-1 expression in rat LSEC is regulated by miR-199, while in human endothelial cells, ET-1 expression is regulated by miR-199 and miR-155, indicating that these microRNAs may function as novel negative regulators to control ET-1 transcription and, thus, homeostatic levels of ET-1 to maintain microcirculatory tone. PMID:19783678

  13. Gastroprotective effect of desmosdumotin C isolated from Mitrella kentii against ethanol-induced gastric mucosal hemorrhage in rats: possible involvement of glutathione, heat-shock protein-70, sulfhydryl compounds, nitric oxide, and anti-Helicobacter pylori activity

    PubMed Central

    2013-01-01

    Background Mitrella kentii (M. kentii) (Bl.) Miq, is a tree-climbing liana that belongs to the family Annonaceae. The plant is rich with isoquinoline alkaloids, terpenylated dihydrochalcones and benzoic acids and has been reported to possess anti-inflammatory activity. The purpose of this study is to assess the gastroprotective effects of desmosdumotin C (DES), a new isolated bioactive compound from M. kentii, on gastric ulcer models in rats. Methods DES was isolated from the bark of M. kentii. Experimental rats were orally pretreated with 5, 10 and 20 mg/kg of the isolated compound and were subsequently subjected to absolute ethanol-induced acute gastric ulcer. Gross evaluation, mucus content, gastric acidity and histological gastric lesions were assessed in vivo. The effects of DES on the anti-oxidant system, non-protein sulfhydryl (NP-SH) content, nitric oxide (NO)level, cyclooxygenase-2 (COX-2) enzyme activity, bcl-2-associated X (Bax) protein expression and Helicabacter pylori (H pylori) were also investigated. Results DES pre-treatment at the administered doses significantly attenuated ethanol-induced gastric ulcer; this was observed by decreased gastric ulcer area, reduced or absence of edema and leucocytes infiltration compared to the ulcer control group. It was found that DES maintained glutathione (GSH) level, decreased malondialdehyde (MDA) level, increased NP-SH content and NO level and inhibited COX-2 activity. The compound up regulated heat shock protein-70 (HSP-70) and down regulated Bax protein expression in the ulcerated tissue. DES showed interesting anti-H pylori effects. The efficacy of DES was accomplished safely without any signs of toxicity. Conclusions The current study reveals that DES demonstrated gastroprotective effects which could be attributed to its antioxidant effect, activation of HSP-70 protein, intervention with COX-2 inflammatory pathway and potent anti H pylori effect. PMID:23866830

  14. Hepatic Arterial Infusion with Tumor Necrosis Factor-? Induces Early Hepatic Hyperperfusion

    Microsoft Academic Search

    T. Schäfer; J. Sperling; J. E. Slotta; O. Kollmar; M. K. Schilling; M. D. Menger; S. Richter

    2012-01-01

    Background: Hepatic arterial infusion (HAI) has been developed for high-dose regional chemotherapy of unresectable liver metastases or primary liver malignancies. While it is well known that high concentrations of tumor necrosis factor (TNF)-? damage tumor blood perfusion, there is no information on whether autochthonous liver perfusion is affected by HAI with TNF-?. Therefore, we investigated the effects of HAI with

  15. Influence of different hepatitis C virus genotypes on the course of asymptomatic hepatitis C virus infection

    Microsoft Academic Search

    D Prati; C Capelli; A Zanella; F Mozzi; P Bosoni; M Pappalettera; F Zanuso; L Vianello; E Locatelli; C de Fazio; G Ronchi; E del Ninno; M Colombo; G Sirchia

    1996-01-01

    BACKGROUND & AIMS: The association of liver disease with hepatitis C virus (HCV) genotypes mainly refers to patients with serious liver damage; little information is available on symptomless carriers. The aim of this study was to investigate the correlation of genotypes with clinical course, risk factors for infection, and antibody to HCV reactivity in asymptomatic subjects. METHODS: One hundred nine

  16. Hepatitis B (HBV)

    MedlinePLUS

    ... special immune injection and the first dose of hepatitis B vaccine at birth. How Is It Prevented? Because people ... B virus. Doctors recommend that teens get a hepatitis B immunization (vaccine). It's a series of three shots over a ...

  17. Hepatitis C (image)

    MedlinePLUS

    Hepatitis C is a virus-caused liver inflammation which may cause jaundice, fever and cirrhosis. Persons who are most at risk for contracting and spreading hepatitis C are those who share needles for injecting drugs ...

  18. Hepatitis B and Hepatitis C in Pregnancy

    MedlinePLUS

    ... any symptoms. In a small number of carriers, chronic infection can lead to serious complications, such as cirrhosis of the liver, liver cancer, and early death. Can hepatitis B virus infection be cured? There is no cure for hepatitis B virus infection, but symptoms can ...

  19. Tornado Damage!

    NSDL National Science Digital Library

    2014-09-18

    Students learn about tornadoes, the damage they cause, and how to rate tornadoes. Specifically, students investigate the Enhanced Fujita Damage Scale of tornado intensity, and use it to complete a mock engineering analysis of damage caused by a tornado. Additional consideration is given to tornado warning systems and how these systems can be improved to be safer. Lastly, students learn basic tornado safety procedures.

  20. Pathogenesis of Hepatic Encephalopathy

    PubMed Central

    Cie?ko-Michalska, Irena; Szczepanek, Ma?gorzata; S?owik, Agnieszka; Mach, Tomasz

    2012-01-01

    Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO) on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy. PMID:23316223

  1. Geranylgeraniol and b-ionone inhibit hepatic preneoplastic lesions, cell proliferation, total plasma cholesterol and DNA damage during the initial phases of hepatocarcinogenesis, but only the former inhibits NF-kB activation

    Microsoft Academic Search

    Roseli de Moura Espindola; Rogeerio Pietro Mazzantini; Thomas Prates Ong; Aline de Conti; Renato Heidor; Fernando Salvador Moreno

    2005-01-01

    occupied by persistent hepatic placental glutathione S-transferase positive preneoplastic lesions (PNL) were reduced in the GGO8 (11 ? 9; 0.26 ? 0.35; 2.7 ? 3.0), GGO16 (6 ? 6; 0.18 ? 0.16; 0.9 ? 0.9), BI8 (9 ? 5; 0.13 ? 0.20; 1.1 ? 1.2) and BI16 (8 ? 6; 0.08 ? 0.09; 0.6 ? 0.4) groups compared with the

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

    PubMed

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

    2008-07-01

    More than 500 million people worldwide are persistently infected with hepatitis B virus or hepatitis C virus. Although both viruses are poorly cytopathic, persistence of either virus carries a risk of chronic liver inflammation, potentially resulting in liver steatosis, liver cirrhosis, end-stage liver failure or hepatocellular carcinoma. Virus-specific T cells are a major determinant of the outcome of hepatitis, as they contribute to the early control of chronic hepatitis viruses, but they also mediate immunopathology during persistent virus infection. We have analyzed the role of platelet-derived vasoactive serotonin during virus-induced CD8(+) T cell-dependent immunopathological hepatitis in mice infected with the noncytopathic lymphocytic choriomeningitis virus. After virus infection, platelets were recruited to the liver, and their activation correlated with severely reduced sinusoidal microcirculation, delayed virus elimination and increased immunopathological liver cell damage. Lack of platelet-derived serotonin in serotonin-deficient mice normalized hepatic microcirculatory dysfunction, accelerated virus clearance in the liver and reduced CD8(+) T cell-dependent liver cell damage. In keeping with these observations, serotonin treatment of infected mice delayed entry of activated CD8(+) T cells into the liver, delayed virus control and aggravated immunopathological hepatitis. Thus, vasoactive serotonin supports virus persistence in the liver and aggravates virus-induced immunopathology. PMID:18516052

  3. Role of viral factors in the natural course and therapy of chronic hepatitis B

    Microsoft Academic Search

    Jia-Horng Kao

    2007-01-01

    Hepatitis B virus (HBV) infection is a global health problem that causes a wide spectrum of liver disease, including acute\\u000a or fulminant hepatitis, inactive carrier state, chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The pathogenesis\\u000a of hepatocyte damage associated with HBV is mainly through immune-mediated mechanisms. On the basis of the virus and host\\u000a interactions, the natural history of HBV

  4. Chronic ethanol consumption disrupts diurnal rhythms of hepatic glycogen metabolism in mice.

    PubMed

    Udoh, Uduak S; Swain, Telisha M; Filiano, Ashley N; Gamble, Karen L; Young, Martin E; Bailey, Shannon M

    2015-06-01

    Chronic ethanol consumption has been shown to significantly decrease hepatic glycogen content; however, the mechanisms responsible for this adverse metabolic effect are unknown. In this study, we examined the impact chronic ethanol consumption has on time-of-day-dependent oscillations (rhythms) in glycogen metabolism processes in the liver. For this, male C57BL/6J mice were fed either a control or ethanol-containing liquid diet for 5 wk, and livers were collected every 4 h for 24 h and analyzed for changes in various genes and proteins involved in hepatic glycogen metabolism. Glycogen displayed a robust diurnal rhythm in the livers of mice fed the control diet, with the peak occurring during the active (dark) period of the day. The diurnal glycogen rhythm was significantly altered in livers of ethanol-fed mice, with the glycogen peak shifted into the inactive (light) period and the overall content of glycogen decreased compared with controls. Chronic ethanol consumption further disrupted diurnal rhythms in gene expression (glycogen synthase 1 and 2, glycogenin, glucokinase, protein targeting to glycogen, and pyruvate kinase), total and phosphorylated glycogen synthase protein, and enzyme activities of glycogen synthase and glycogen phosphorylase, the rate-limiting enzymes of glycogen metabolism. In summary, these results show for the first time that chronic ethanol consumption disrupts diurnal rhythms in hepatic glycogen metabolism at the gene and protein level. Chronic ethanol-induced disruption in these daily rhythms likely contributes to glycogen depletion and disruption of hepatic energy homeostasis, a recognized risk factor in the etiology of alcoholic liver disease. PMID:25857999

  5. Nutritional management of hepatic disease.

    PubMed

    Bauer, J E; Schenck, P A

    1989-05-01

    The successful management of hepatic diseases of dogs and cats requires an understanding of hepatic metabolism and nutritional processes. General aspects of dietary therapy for hepatic diseases are described, along with specific recommendations for the promotion of tissue regeneration. Special considerations, including the role of diet in encephalopathy, hepatic lipidosis, and copper-associated hepatic toxicosis, are also discussed. PMID:2658288

  6. Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis

    Microsoft Academic Search

    D. Keith George; Stefano Goldwurm; Graeme A. Macdonald; Lex L. Cowley; Neal I. Walker; Patrick J. Ward; Elizabeth C. Jazwinska; Lawrie W. Powell

    1998-01-01

    Background & Aims: Nonalcoholic steatohepatitis (NASH) is a chronic liver disease that occasionally progresses to cirrhosis but usually has a benign course. The aim of this study was to investigate the role of the hemochromatosis mutation Cys282Tyr in development of the mild hepatic iron overload found in some patients with NASH and its association with hepatic damage in these patients.

  7. Increasing numbers of hepatic dendritic cells promote HMGB1-mediated ischemia-reperfusion injury

    Microsoft Academic Search

    Allan Tsung; Ning Zheng; Geetha Jeyabalan; Kunihiko Izuishi; John R. Klune; David A. Geller; Michael T. Lotze; Lina Lu; Timothy R. Billiar

    2006-01-01

    Endogenous ligands released from damaged cells, so-called damage-associated molec- ular pattern molecules (DAMPs), activate innate signaling pathways including the TLRs. We have shown that hepatic, warm ischemia and reperfusion (I\\/R) injury, generating local, noninfectious DAMPs, promotes inflammation, which is largely TLR4-de- pendent. Here, we demonstrate that increasing den- dritic cell (DC) numbers enhance inflammation and organ injury after hepatic I\\/R.

  8. Reversed light-dark cycle and cage enrichment effects on ethanol-induced deficits in motor coordination assessed in inbred mouse strains with a compact battery of refined tests

    PubMed Central

    Munn, Elizabeth; Bunning, Mark; Prada, Sofia; Bohlen, Martin; Crabbe, John C.; Wahlsten, Douglas

    2011-01-01

    The laboratory environment existing outside the test situation itself can have a substantial influence on results of some behavioral tests with mice, and the extent of these influences sometimes depends on genotype. For alcohol research, the principal issue is whether genotype-related ethanol effects will themselves be altered by common variations in the lab environment or instead will be essentially the same across a wide range of lab environments. Data from 20 inbred strains were used to reduce an original battery of seven tests of alcohol intoxication to a compact battery of four tests: the balance beam and grip strength with a 1.25 g/kg ethanol dose and the accelerating rotarod and open-field activation tests with 1.75 g/kg. The abbreviated battery was then used to study eight inbred strains housed under a normal or reversed light-dark cycle, or a standard or enriched home cage environment. The light-dark cycle had no discernable effects on any measure of behavior or response to alcohol. Cage enrichment markedly improved motor coordination in most strains. Ethanol-induced motor coordination deficits were robust; the well documented strain-dependent effects of ethanol were not altered by cage enrichment. PMID:21664382

  9. [Hepatic artery embolization for primary hepatic carcinoma].

    PubMed

    Ye, W J

    1989-03-01

    Twenty patients with primary hepatic carcinoma (PHC) treated by hepatic arterial embolization in our department from Dec. 1986 to Mar. 1987 are reported. There were 15 males and 5 females. The ages ranged from 34 to 75 years with an average of 50.7. Preoperative diagnosis and localization of the tumor were done by AFP, B-us, CT and angiography (right lobe 15 cases, left lobe 1 case, both lobes 4 cases). Celiac and superior mesenteric angiography was carried out by femoral artery approach and then highly selective hepatic catheterization was utilized for hepatic arterial embolization. Antitumor agent (5-Fu, adriamycin), iophendylate and foamy gel sponge were used for peripheral and proximal embolization. Manifestations were improved in most of the patients after embolization, such as relief of abdominal pain, improvement of appetite, decrease of tumor size. Total necrosis of the tumor was found in 2 patients who underwent surgery 1 month after embolization. The side effects of the posthepatic embolization such as, nausea, vomiting, abdominal pain and fever could be relieved by symptomatic treatment. No severe complications, such as gangrene of the gall bladder, hepatic failure, liver abscess, intestinal necrosis or pulmonary embolization were found except 3 patients who died of renal failure after the procedure. The liver dys-function returned to normal within 2 weeks. Hepatic arterial embolization provides an alternative treatment for the patients with PHC who has compensated liver function without severe systemic diseases, especially renal endocrine problems and severe portal hypertension. They should have patent portal system as proved by angiography. The authors considered that this therapeutic embolization with hepatic chemotherapy infusion is safe and effective in the management of PHC. It may increase the resectability and provide palliative means for the advanced and terminal cases. PMID:2553366

  10. Moderate, chronic ethanol feeding exacerbates carbon tetrachloride–induced hepatic fibrosis via hepatocyte-specific hypoxia-inducible factor 1?

    PubMed Central

    Roychowdhury, Sanjoy; Chiang, Dian J; McMullen, Megan R; Nagy, Laura E

    2014-01-01

    The hypoxia-sensing transcriptional factor HIF1? is implicated in a variety of hepato-pathological conditions; however, the contribution of hepatocyte-derived HIF1? during progression of alcoholic liver injury is still controversial. HIF1? induces a variety of genes including those involved in apoptosis via p53 activation. Increased hepatocyte apoptosis is critical for progression of liver inflammation, stellate cell activation, and fibrosis. Using hepatocyte-specific HIF1?-deficient mice (?HepHIF1??/?), here we investigated the contribution of HIF1? to ethanol-induced hepatocyte apoptosis and its role in amplification of fibrosis after carbon tetrachloride (CCl4) exposure. Moderate ethanol feeding (11% of kcal) induced accumulation of hypoxia-sensitive pimonidazole adducts and HIF1? expression in the liver within 4 days of ethanol feeding. Chronic CCl4 treatment increased M30-positive cells, a marker of hepatocyte apoptosis in pair-fed control mice. Concomitant ethanol feeding (11% of kcal) amplified CCl4-induced hepatocyte apoptosis in livers of wild-type mice, associated with elevated p53K386 acetylation, PUMA expression, and Ly6c+ cell infiltration. Subsequent to increased apoptosis, ethanol-enhanced induction of profibrotic markers, including stellate cell activation, collagen 1 expression, and extracellular matrix deposition following CCl4 exposure. Ethanol-induced exacerbation of hepatocyte apoptosis, p53K386 acetylation, and PUMA expression following CCl4 exposure was attenuated in livers of ?HepHIF1??/? mice. This protection was also associated with a reduction in Ly6c+ cell infiltration and decreased fibrosis in livers of ?HepHIF1??/? mice. In summary, these results indicate that moderate ethanol exposure leads to hypoxia/HIF1?-mediated signaling in hepatocytes and induction of p53-dependent apoptosis of hepatocytes, resulting in increased hepatic fibrosis during chronic CCl4 exposure. PMID:25089199

  11. Hepatitis Foundation International

    MedlinePLUS

    ... profit organization established in 1994 working to eradicate chronic hepatitis for 400 million people globally. HFI is also ... Your Information. Our best hope for treatments and cures is your participation in the Hepatitis Foundation International Registry. Whether you are affected, a ...

  12. Alcohol and Hepatitis C

    Microsoft Academic Search

    M. Mazen Jamal; Zainab Saadi; Timothy R. Morgan

    2005-01-01

    Background\\/Aims: Alcohol use and hepatitis C are prominent risk factors for liver injury and this review offers the current understanding of each factor’s effects on liver disease. Methods: A Medline database search was preformed for English articles with a focus on alcohol, hepatitis C and liver disease. Article citations were also considered for further applicable articles, and the strongest studies

  13. Yellow discoloration in veal calves: the role of hepatic copper.

    PubMed

    Groot, M J; Gruys, E

    1993-02-13

    Liver samples from four groups of calves were analysed chemically and histologically for copper and iron levels. Milk replacer-fed 'yellow' calves were compared with milk replacer-fed 'white' calves, concentrate and silage-fed 'pink' calves and concentrate and silage-fed young 'red' fattening bulls. In the milk replacer-fed calves high copper and low iron levels were measured in the liver, whereas in the concentrate and silage fed pink calves and fattening bulls lower copper and higher iron levels were found. The yellow calves appeared to be icteric and had chronic hepatitis. Their hepatic histopathology was characterised by fibrosis, cirrhosis, fatty change, increased amounts of stainable copper, necrobiosis and prominent cholestasis; some animals had intranuclear inclusion bodies in the hepatocytes. They had similar or lower hepatic copper levels than the white calves and varying iron levels, indicating that copper toxicity was not the primary cause of the hepatic damage. PMID:8456546

  14. DNA structure in peripheral blood lymphocytes from patients with chronic viral liver damages.

    PubMed

    Reshetnyak, V I; Sharafanova, T I; Il'chenko, L Yu; Poroshenko, G G

    2002-04-01

    We studied DNA damages (single-strand breaks and alkali-labile sites) in peripheral blood lymphocytes from patients with chronic viral hepatitis and cirrhosis of mixed etiology. The structure of DNA was estimated fluorometrically by changes in the intensity of ethidium bromide fluorescence. Monoinfection with hepatitis B and C viruses was not accompanied by considerable changes in DNA structure in peripheral blood lymphocytes from patients with chronic diseases. The incidence of DNA damages in lymphocytes increased in patients with hepatitis G virus and TTV monoinfection. This is probably related to replication of these viruses in nucleated blood cells. Our results suggest that hepatitis C virus potentiates damaging effect of hepatitis G virus on DNA in lymphocytes. PMID:12124657

  15. Regulation of Hepatic Lipin-1 by Ethanol: Role of AMPK-SREBP-1 Signaling

    PubMed Central

    Hu, Ming; Wang, Fengming; Li, Xin; Rogers, Christopher Q.; Liang, Xiaomei; Finck, Brian N.; Mitra, Mayurranjan S.; Zhang, Ray; Mitchell, Dave A.; You, Min

    2011-01-01

    Lipin-1 is a protein that exhibits dual functions as a phosphatidic acid phosphohydrolase (PAP) enzyme in the triglyceride synthesis pathways and a transcriptional co-regulator. Our previous studies have shown that ethanol causes fatty liver by activation of sterol regulatory element-binding protein 1 (SREBP-1) and inhibition of hepatic AMP-activated kinase (AMPK) in mice. Here, we tested the hypothesis that AMPK-SREBP-1 signaling may be involved in ethanol-mediated up-regulation of lipin-1 gene expression. The effects of ethanol on lipin-1 were investigated in cultured hepatic cells and in the livers of chronic ethanol-fed mice. Ethanol exposure robustly induced activity of a mouse lipin-1 promoter, promoted cytoplasmic localization of lipin-1 and caused excess lipid accumulation both in cultured hepatic cells and in mouse livers. Mechanistic studies showed that ethanol-mediated induction of lipin-1 gene expression was inhibited by a known activator of AMPK or overexpression of a constitutively active form of AMPK. Importantly, overexpression of processed nuclear form of SREBP-1c (nSREBP-1c) abolished the ability of AICAR to suppress ethanol-mediated induction of lipin-1 gene expression level. Chromatin immunoprecipitation (ChIP) assays further revealed that ethanol exposure significantly increased association of acetylated Histone H3 at lysine 9 (Lys9) with the SRE-containing region in the promoter of the lipin-1 gene. In conclusion, ethanol-induced up-regulation of lipin-1 gene expression is mediated through inhibition of AMPK and activation of SREBP-1. PMID:21953514

  16. ALLYLISOPROPYLACETAMIDE INDUCES RAT HEPATIC ORNITHINE DECARBOXYLASE (JOURNAL VERSION)

    EPA Science Inventory

    Allylisopropylacetamide (AIA) did not cause DNA damage in rat liver. The porphyrinogenic research drug did strongly induce the activity (25-fold) of rat hepatic enzyme ornithine decarboxylase (ODC). By either the oral or the subcutaneous route AIA produced a long lasting inductio...

  17. Hepatitis E virus infection in acute hepatitis in Spain

    Microsoft Academic Search

    Maria Buti; Rosendo Jardí; Montserrat Cotrina; Francisco Rodríguez-Frías; Hugo Troonen; Luis Viladomiu; J. I. Esteban; Rafael Esteban; Jaime Guardia

    1995-01-01

    In order to study the prevalence of hepatitis E virus (HEV) infection in developed countries, IgG and IgM anti-HEV were determined in serum samples from 382 patients with acute viral hepatitis (244 hepatitis A, 48 hepatitis B and\\/or D, and 90 non-A, non-B, non-C hepatitis), 76 healthy subjects, 55 hemophiliacs and 50 patients on hemodialysis. IgG anti-HEV antibodies were detected

  18. DNA Structure in Peripheral Blood Lymphocytes from Patients with Chronic Viral Liver Damages

    Microsoft Academic Search

    V. I. Reshetnyak; T. I. Sharafanova; L. Yu. Il'chenko; G. G. Poroshenko

    2002-01-01

    We studied DNA damages (single-strand breaks and alkali-labile sites) in peripheral blood lymphocytes from patients with chronic viral hepatitis and cirrhosis of mixed etiology. The structure of DNA was estimated fluorometrically by changes in the intensity of ethidium bromide fluorescence. Monoinfection with hepatitis B and C viruses was not accompanied by considerable changes in DNA structure in peripheral blood lymphocytes

  19. Chemoembolization of hepatic malignancy

    Microsoft Academic Search

    Carin F. Gonsalves; Daniel B. Brown

    2009-01-01

    Treatment of primary and secondary hepatic malignancies with transarterial chemoembolization represents an essential component\\u000a of interventional oncology. This article discusses patient selection, procedure technique, results, and complications associated\\u000a with transarterial chemoembolization.

  20. Chemoembolization of hepatic malignancy

    Microsoft Academic Search

    Carin F. Gonsalves; Daniel B. Brown

    Treatment of primary and secondary hepatic malignancies with transarterial chemoembolization (TACE) represents an essential\\u000a component of interventional oncology. This article discusses patient selection, procedure technique, results, and complications\\u000a associated with TACE.

  1. Hepatitis C: Mental Health

    MedlinePLUS

    ... a headache or other physical problem. Taking some deep breaths also releases tension. Coping tips It is completely normal to have an emotional reaction upon learning that you have hepatitis C, such as anxiety, ...

  2. Drug-induced hepatitis

    MedlinePLUS

    ... induced hepatitis. Painkillers and fever reducers that contain acetaminophen are a common cause of liver inflammation. These ... problem. However, if you took high doses of acetaminophen , treatment should be started as soon as possible ...

  3. Hepatitis Risk Assessment

    MedlinePLUS

    ... About the Division of Viral Hepatitis Contact Us File Formats Help: How do I view different file formats (PDF, DOC, PPT, MPEG) on this site? Adobe PDF file Microsoft PowerPoint file Microsoft Word file Microsoft Excel ...

  4. Viral Hepatitis: A through E and Beyond

    MedlinePLUS

    ... travelers How can hepatitis B be prevented? The hepatitis B vaccine offers the best protection. All infants and unvaccinated ... should receive hepatitis B immune globulin and the hepatitis B vaccine within 12 hours of birth to help prevent ...

  5. Hepatitis A Also Known As Hep A

    MedlinePLUS

    ... 2013 Hepatitis A Hepatitis A is a contagious viral infection that can easily affect children and adults. It is one of the most common types of hepatitis virus. Often when you hear about hepatitis A it ...

  6. Hepatitis b vaccination

    Microsoft Academic Search

    Albert D. Min; Aaron Walfish; Henry C. Bodenheimer

    2006-01-01

    Hepatitis B virus (HBV)infection is a major cause of chronic hepatitis and cirrhosis,with an estimated 350 million people\\u000a worldwide infected with the virus.Despite continuing advances in antiviral therapy,a cure for chronic HBV infection is considered\\u000a an elusive goal.Thus,primary prevention by immunization with HBV vaccines remains the most effective means to control the\\u000a transmission of HBV infection.

  7. Torsed pedunculated hepatic hamartoma

    Microsoft Academic Search

    Ignacio Vázquez-Lima; José L. Vázquez; Marta Gallego; Rebeca Fernández; Pilar Fernández

    2009-01-01

    We report a 9-year-old boy with a 6-h history of acute abdominal pain due to torsion of a pedunculated hepatic mesenchymal\\u000a hamartoma. The lesion was seen, on US and CT, to connect to the liver through a pedicle. Mesenchymal hepatic hamartomas are\\u000a unusual tumours that may be pedunculated, and this is a unique case complicated by torsion. The radiological and

  8. Foetal hepatic calcification

    Microsoft Academic Search

    N. D. Hawass; M. G. El Badawi; J. A. Fatani; A. Al-Meshari; D. Makanjoula; Y. B. Edress

    1990-01-01

    Thirty-three cases of 1,500 spontaneously-aborted foetuses showed hepatic calcifications. The exact location of these calcifications were confirmed by contrast studies, anatomic dissection, and further histology when necessary. Of them, 18 were calcified hepatic vein thrombi (CHVT), 12 were calcified portal vein thrombi (CPVT), 2 were parenchymal calcifications, and one was mixed. Associated anomalies were high (85% of cases). No significant

  9. Solitary Hepatic Lymphangioma

    PubMed Central

    Stavropoulos, M.; Vagianos, C.; Scopa, C. D.; Dragotis, C.; Androulakis, J.

    1994-01-01

    Hepatic lymphangiomas are extremely rare; moreover cystic lymphangiomas usually arise in areas such as the neck and axilla, where loose connective tissue allows the expansion of lymphatic channels. The case of a 65-year old male is described, who presented with a solitary lymphangioma in the liver. The lesion was discovered incidentally and due to diagnostic uncertainty was removed surgically. A short review of histology, clinical presentation and preoperative diagnostic difficulties of hepatic lymphangiomas is given. PMID:7993862

  10. Sex Differences in Hepatic Gluconeogenic Capacity After Chronic Alcohol Consumption

    PubMed Central

    Sumida, Ken D.; Hill, Janeen M.; Matveyenko, Aleksey V.

    2007-01-01

    Alcohol-induced hypoglycemia has traditionally been attributed to the amount of ethanol consumed rather than any inherent decline in glucose output capacity by the gluconeogenic organs and/or an increase in skeletal muscle glucose uptake. Further, while the potential for sex differences that might impact glucose homeostasis following chronic alcohol consumption has been recognized, direct evidence has been noticeably absent. This paper will provide a brief review of past and present reports of the potential for sex differences in glucose homeostasis following chronic ethanol consumption. This paper will also provide direct evidence from our laboratory demonstrating sex differences from chronic alcohol consumption resulting in a decrement in glucose appearance and more importantly, a specific decline in hepatic gluconeogenic (HGN) capacity in the absence and presence of ethanol. All our studies involved 8 weeks of chronic alcohol consumption in male and female Wistar rats, as well as a 24 to 48 hour fast to deplete hepatic glycogen stores. Under the conditions of chronic alcohol consumption and an acute dose of ethanol, we provide in vivo evidence of an early decline in whole body glucose appearance in females fed an ethanol diet compared to controls. While the decline was also observed in males fed the alcohol diet, it occurred much later compared to ethanol fed females. The site for the decline in whole body glucose production (i.e., either the kidneys or the liver) was beyond the scope of our prior in vivo study. In a follow-up study using the in situ perfused liver preparation, we provide additional evidence for a specific reduction in HGN capacity from lactate in ethanol fed females compared to ethanol fed males in the absence of alcohol in the perfusion medium. Finally, employing the isolated hepatocyte technique, we report decrements in HGN from lactate in ethanol fed females compared to ethanol fed males in the presence of ethanol in the incubation medium. The mechanism for the specific decline in HGN within the liver of ethanol fed females remains to be determined. To the extent that our observations in animals can be extrapolated to humans, we conclude that alcoholic women are more susceptible to ethanol-induced hypoglycemia compared to alcoholic men. PMID:18056029

  11. Antioxidant activities of isoflavones from the rhizomes of belamcanda chinensis on carbon tetrachloride-lnduced hepatic injury in rats

    Microsoft Academic Search

    Sang Hoon Jung; Yeon Sil Lee; Soon Sung Lim; Sanghyun Lee; Kuk Hyun Shin; Yeong Shik Kim

    2004-01-01

    The present study was carried out to clarify whether tectorigenin and tectoridin isolated from the rhizomes ofBelamcanda chinensis (Iridaceae) inhibit hepatic damage induced by carbon tetrachloride (CCI+4)-intoxication in rats by the experimental methodsin vitro andin vivo. Tectorigenin and tectoridin exhibited a significant decrease in serum transaminase activities elevated by hepatic damage\\u000a induced by CCI4-intoxication in rats, as well as in

  12. Mechanisms of Hepatic Fibrogenesis

    PubMed Central

    Friedman, Scott L.

    2010-01-01

    Substantial improvements in the treatment of chronic liver disease have accelerated interest in uncovering the mechanisms underlying hepatic fibrosis and its resolution. Activation of resident hepatic stellate cells into proliferative, contractile, and fibrogenic cells in liver injury remains a dominant theme driving the field. However, several new areas of rapid progress in the past 5–10 years also have taken root, including: (1) identification of different fibrogenic populations apart from resident stellate cells, for example, portal fibroblasts, fibrocytes, and bone-marrow– derived cells, as well as cells derived from epithelial mesenchymal transition; (2) emergence of stellate cells as finely regulated determinants of hepatic inflammation and immunity; (3) elucidation of multiple pathways controlling gene expression during stellate cell activation including transcriptional, post-transcriptional, and epigenetic mechanisms; (4) recognition of disease-specific pathways of fibrogenesis; (5) re-emergence of hepatic macrophages as determinants of matrix degradation in fibrosis resolution and the importance of matrix cross-linking and scar maturation in determining reversibility; and (6) hints that hepatic stellate cells may contribute to hepatic stem cell behavior, cancer, and regeneration. Clinical and translational implications of these advances have become clear, and have begun to impact significantly on the management and outlook of patients with chronic liver disease. PMID:18471545

  13. Immigration and viral hepatitis.

    PubMed

    Sharma, Suraj; Carballo, Manuel; Feld, Jordan J; Janssen, Harry L A

    2015-08-01

    WHO estimates reveal that the global prevalence of viral hepatitis may be as high as 500million, with an annual mortality rate of up to 1.3million individuals. The majority of this global burden of disease is borne by nations of the developing world with high rates of vertical and iatrogenic transmission of HBV and HCV, as well as poor access to healthcare. In 2013, 3.2% of the global population (231million individuals) migrated into a new host nation. Migrants predominantly originate from the developing countries of the south, into the developed economies of North America and Western Europe. This mass migration of individuals from areas of high-prevalence of viral hepatitis poses a unique challenge to the healthcare systems of the host nations. Due to a lack of universal standards for screening, vaccination and treatment of viral hepatitis, the burden of chronic liver disease and hepatocellular carcinoma continues to increase among migrant populations globally. Efforts to increase case identification and treatment among migrants have largely been limited to small outreach programs in urban centers, such that the majority of migrants with viral hepatitis continue to remain unaware of their infection. This review summarizes the data on prevalence of viral hepatitis and burden of chronic liver disease among migrants, current standards for screening and treatment of immigrants and refugees, and efforts to improve the identification and treatment of viral hepatitis among migrants. PMID:25962882

  14. Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

    SciTech Connect

    Wu, Weibin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China) [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Science, Fudan University, Shanghai 200032 (China); Zhu, Bo; Peng, Xiaomin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China)] [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Zhou, Meiling, E-mail: meilingzhou2012@gmail.com [Department of Radiology, Zhongshan Hospital of Fudan University and Shanghai Institute of Medical Imaging, Shanghai 200032 (China)] [Department of Radiology, Zhongshan Hospital of Fudan University and Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Jia, Dongwei, E-mail: jiadongwei@fudan.edu.cn [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China)] [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Gu, Jianxin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China) [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Science, Fudan University, Shanghai 200032 (China)

    2014-01-03

    Highlights: •FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. •Activation of FXR attenuated alcohol-induced liver injury and steatosis. •Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients.

  15. Mangafodipir Protects against Hepatic Ischemia-Reperfusion Injury in Mice

    PubMed Central

    Coriat, Romain; Leconte, Mahaut; Kavian, Niloufar; Bedda, Sassia; Nicco, Carole; Chereau, Christiane; Goulvestre, Claire; Weill, Bernard

    2011-01-01

    Introduction and Aim Mangafodipir is a contrast agent used in magnetic resonance imaging that concentrates in the liver and displays pleiotropic antioxidant properties. Since reactive oxygen species are involved in ischemia-reperfusion damages, we hypothesized that the use of mangafodipir could prevent liver lesions in a mouse model of hepatic ischemia reperfusion injury. Mangafodipir (MnDPDP) was compared to ischemic preconditioning and intermittent inflow occlusion for the prevention of hepatic ischemia-reperfusion injury in the mouse. Methods Mice were subjected to 70% hepatic ischemia (continuous ischemia) for 90 min. Thirty minutes before the ischemic period, either mangafodipir (10 mg/kg) or saline was injected intraperitoneally. Those experimental groups were compared with one group of mice preconditioned by 10 minutes' ischemia followed by 15 minutes' reperfusion, and one group with intermittent inflow occlusion. Hepatic ischemia-reperfusion injury was evaluated by measurement of serum levels of aspartate aminotransferase (ASAT) activity, histologic analysis of the livers, and determination of hepatocyte apoptosis (cytochrome c release, caspase 3 activity). The effect of mangafodipir on the survival rate of mice was studied in a model of total hepatic ischemia. Results Mangafodipir prevented experimental hepatic ischemia-reperfusion injuries in the mouse as indicated by a reduction in serum ASAT activity (P<0.01), in liver tissue damages, in markers of apoptosis (P<0.01), and by higher rates of survival in treated than in untreated animals (P<0.001). The level of protection by mangafodipir was similar to that observed following intermittent inflow occlusion and higher than after ischemic preconditioning. Conclusions Mangafodipir is a potential new preventive treatment for hepatic ischemia-reperfusion injury. PMID:22073237

  16. Metabolomic biomarkers correlating with hepatic lipidosis in dairy cows

    PubMed Central

    2014-01-01

    Background Hepatic lipidosis or fatty liver disease is a major metabolic disorder of high-producing dairy cows that compromises animal performance and, hence, causes heavy economic losses worldwide. This syndrome, occurring during the critical transition from gestation to early lactation, leads to an impaired health status, decreased milk yield, reduced fertility and shortened lifetime. Because the prevailing clinical chemistry parameters indicate advanced liver damage independently of the underlying disease, currently, hepatic lipidosis can only be ascertained by liver biopsy. We hypothesized that the condition of fatty liver disease may be accompanied by an altered profile of endogenous metabolites in the blood of affected animals. Results To identify potential small-molecule biomarkers as a novel diagnostic alternative, the serum samples of diseased dairy cows were subjected to a targeted metabolomics screen by triple quadrupole mass spectrometry. A subsequent multivariate test involving principal component and linear discriminant analyses yielded 29 metabolites (amino acids, phosphatidylcholines and sphingomyelines) that, in conjunction, were able to distinguish between dairy cows with no hepatic lipidosis and those displaying different stages of the disorder. Conclusions This proof-of-concept study indicates that metabolomic profiles, including both amino acids and lipids, distinguish hepatic lipidosis from other peripartal disorders and, hence, provide a promising new tool for the diagnosis of hepatic lipidosis. By generating insights into the molecular pathogenesis of hepatic lipidosis, metabolomics studies may also facilitate the prevention of this syndrome. PMID:24888604

  17. Classical and Modern Approaches Used for Viral Hepatitis Diagnosis

    PubMed Central

    Heiat, Mohammad; Ranjbar, Reza; Alavian, Seyed Moayed

    2014-01-01

    Context: Viral hepatitis diagnosis is an important issue in the treatment procedure of this infection. Late diagnosis and delayed treatment of viral hepatitis infections can lead to irreversible liver damages and occurrence of liver cirrhosis and hepatocellular carcinoma. A variety of laboratory methods including old and new technologies are being applied to detect hepatitis viruses. Here we have tried to review, categorize, compare and illustrate the classical and modern approaches used for diagnosis of viral hepatitis. Evidence Acquisition: In order to achieve a comprehensive aspect in viral hepatitis detection methods, an extensive search using related keywords was done in major medical library and data were collected, categorized and summarized in different sections. Results: Analyzing of collected data resulted in the wrapping up the hepatitis virus detection methods in separate sections including 1) immunological methods such as enzyme immunoassay (EIA), radio-immunoassay (RIA) immuno-chromatographic assay (ICA), and immuno-chemiluminescence 2) molecular approaches including non-amplification and amplification based methods, and finally 3) advanced biosensors such as mass-sensitive, electrical, electrochemical and optical based biosensors and also new generation of detection methods. Conclusions: Detection procedures in the clinical laboratories possess a large diversity; each has their individual advantages and facilities' differences. PMID:24829586

  18. Ethanol induces hydroxytyrosol formation in humans.

    PubMed

    Pérez-Mañá, Clara; Farré, Magí; Pujadas, Mitona; Mustata, Cristina; Menoyo, Esther; Pastor, Antoni; Langohr, Klaus; de la Torre, Rafael

    2015-01-01

    Previous studies in animals have shown an increase of hydroxytyrosol (OHTyr), a potent phenolic antioxidant and a minor metabolite of dopamine (also called 3,4-dihydroxyphenylethanol or DOPET), after ethanol intake. The interaction between ethanol and dopamine metabolism is the probable mechanism involved. The aim of the study was to establish the contribution of the dose of ethanol on OHTyr formation. 24 healthy male volunteers were included. Subjects were distributed in three different cohorts and each volunteer received two doses of ethanol or placebo. Doses of ethanol administered were 6, 12, 18, 24, 30 and 42g. Study design was double-blind, randomized, crossover and controlled. Hydroxytyrosol, tyrosol (Tyr), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) urinary excretion, ethanol plasma concentrations and drunkenness were evaluated along a 6-h period. Urinary excretion of OHTyr and Tyr increased with ethanol administered dose. A reduction in the ratio DOPAC/OHTyr from placebo to the highest dose was observed, compatible with a shift in the dopamine metabolism to preferently produce OHTyr instead of DOPAC. Also a dose-dependent increase in plasma ethanol concentrations and subjective effects was observed. This study demonstrates an endogenous production of OHTyr and Tyr in relation to ethanol administered dose in humans. Biological effects of both phenols from this source should be investigated in future studies. PMID:25801942

  19. Rescue of Lethal Hepatic Failure by Hepatized Lymph Nodes in Mice

    PubMed Central

    Hoppo, Toshitaka; Komori, Junji; Manohar, Rohan; Stolz, Donna Beer; Lagasse, Eric

    2010-01-01

    BACKGROUND & AIMS Hepatocyte transplantation is a potential therapeutic approach for liver disease. However, most patients with chronic hepatic damage have cirrhosis and fibrosis, which limit the potential for cell-based therapy of the liver. The development of an ectopic liver as an additional site of hepatic function represents a new approach for patients with an end-stage liver disease. We investigated the development and function of liver tissue in lymph nodes in mice with liver failure. METHODS Hepatocytes were isolated from 8 to 12-week-old mice and transplanted by intraperitoneal injection into 8- to 12-week-old Fah-/- mice, a model of the human liver disease tyrosinemia type I. Survival was monitored and the locations and functions of the engrafted liver cells were determined. RESULTS Lymph nodes of Fah-/- mice were colonized by transplanted hepatocytes; Fah+ hepatocytes were detected adjacent to the CD45+ lymphoid cells of the lymphatic system. Ten weeks after transplantation, these mice had substantial improvements in serum levels of transaminases, bilirubin, and amino acids. Homeostatic expansion of donor hepatocytes in lymph nodes rescued the mice from lethal hepatic failure. CONCLUSIONS Functional ectopic liver tissue in lymph nodes rescues mice from lethal hepatic disease; lymph nodes might therefore be used as sites for hepatocyte transplantation. PMID:21070777

  20. The effects of insulin pre-administration in mice exposed to ethanol: alleviating hepatic oxidative injury through anti-oxidative, anti-apoptotic activities and deteriorating hepatic steatosis through SRBEP-1c activation.

    PubMed

    Liu, Jiangzheng; Wang, Xin; Peng, Zhengwu; Zhang, Tao; Wu, Hao; Yu, Weihua; Kong, Deqing; Liu, Ying; Bai, Hua; Liu, Rui; Zhang, Xiaodi; Hai, Chunxu

    2015-01-01

    Alcoholic liver disease (ALD) has become an important liver disease hazard to public and personal health. Oxidative stress is believed to be responsible for the pathological changes in ALD. Previous studies have showed that insulin, a classic regulator of glucose metabolism, has significant anti-oxidative function and plays an important role in maintaining the redox balance. For addressing the effects and mechanisms of insulin pre-administration on ethanol-induced liver oxidative injury, we investigated histopathology, inflammatory factors, apoptosis, mitochondrial dysfunction, oxidative stress, antioxidant defense system, ethanol metabolic enzymes and lipid disorder in liver of ethanol-exposed mice pretreatment with insulin or not. There are several novel findings in our study. First, we found insulin pre-administration alleviated acute ethanol exposure-induced liver injury and inflammation reflected by the decrease of serum AST and ALT activities, the improvement of pathological alteration and the inhibition of TNF-? and IL-6 expressions. Second, insulin pre-administration could significantly reduce apoptosis and ameliorate mitochondrial dysfunction in liver of mice exposed to ethanol, supporting by decreasing caspases-3 activities and the ratio of Bax/Bcl-2, increasing mitochondrial viability and mitochondrial oxygen consumption, inhibition of the decline of ATP levels and mitochondrial ROS accumulation. Third, insulin pre-administration prevented ethanol-mediated oxidative stress and enhance antioxidant defense system, which is evaluated by the decline of MDA levels and the rise of GSH/GSSG, the up-regulations of antioxidant enzymes CAT, SOD, GR through Nrf-2 dependent pathway. Forth, the modification of ethanol metabolism pathway such as the inhibition of CYP2E1, the activation of ALDH might be involved in the anti-oxidative and protective effects exerted by insulin pre-administration against acute ethanol exposure in mice. Finally, insulin pre-administration deteriorated hepatic steatosis in mice exposed to ethanol might be through SRBEP-1c activation. In summary, these results indicated that insulin pre-administration effectively alleviated liver oxidative injury through anti-inflammatory, anti-oxidative and anti-apoptotic activities but also deteriorated hepatic steatosis through SRBEP-1c activation in mice exposed to ethanol. Our study provided novel insight about the effects and mechanisms of insulin on ethanol-induced liver injury. PMID:25892964

  1. Hepatic manifestations during amoebic dysentery

    Microsoft Academic Search

    S. Ramachandran; C. N. A. Rajapakse; R. de Saram; S. Sivalingam

    1973-01-01

    A variety of hepatic manifestations may occur during attacks of acute amoebic dysentery, conforming to clearly defined clinical groups.The incidence of definite hepatic involvement presenting as cases of hepatic amoebiasis with or without demonstrable pus or with tender hepatomegaly was 57·5%.While it is possible that the cases presenting with hepatic manifestations without demonstrable pus are due to small deep-seated abscesses,

  2. Pancreatic injury in hepatic alcohol dehydrogenase-deficient deer mice after subchronic exposure to ethanol

    SciTech Connect

    Kaphalia, Bhupendra S., E-mail: bkaphali@utmb.ed [Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555 (United States); Bhopale, Kamlesh K.; Kondraganti, Shakuntala; Wu Hai; Boor, Paul J.; Ansari, G.A. Shakeel [Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555 (United States)

    2010-08-01

    Pancreatitis caused by activation of digestive zymogens in the exocrine pancreas is a serious chronic health problem in alcoholic patients. However, mechanism of alcoholic pancreatitis remains obscure due to lack of a suitable animal model. Earlier, we reported pancreatic injury and substantial increases in endogenous formation of fatty acid ethyl esters (FAEEs) in the pancreas of hepatic alcohol dehydrogenase (ADH)-deficient (ADH{sup -}) deer mice fed 4% ethanol. To understand the mechanism of alcoholic pancreatitis, we evaluated dose-dependent metabolism of ethanol and related pancreatic injury in ADH{sup -} and hepatic ADH-normal (ADH{sup +}) deer mice fed 1%, 2% or 3.5% ethanol via Lieber-DeCarli liquid diet daily for 2 months. Blood alcohol concentration (BAC) was remarkably increased and the concentration was {approx} 1.5-fold greater in ADH{sup -} vs. ADH{sup +} deer mice fed 3.5% ethanol. At the end of the experiment, remarkable increases in pancreatic FAEEs and significant pancreatic injury indicated by the presence of prominent perinuclear space, pyknotic nuclei, apoptotic bodies and dilation of glandular ER were found only in ADH{sup -} deer mice fed 3.5% ethanol. This pancreatic injury was further supported by increased plasma lipase and pancreatic cathepsin B (a lysosomal hydrolase capable of activating trypsinogen), trypsinogen activation peptide (by-product of trypsinogen activation process) and glucose-regulated protein 78 (endoplasmic reticulum stress marker). These findings suggest that ADH-deficiency and high alcohol levels in the body are the key factors in ethanol-induced pancreatic injury. Therefore, determining how this early stage of pancreatic injury advances to inflammation stage could be important for understanding the mechanism(s) of alcoholic pancreatitis.

  3. 6 Immunopathogenesis of viral hepatitis

    Microsoft Academic Search

    Barbara Rehermann

    1996-01-01

    More than 500 million people world-wide suffer from viral hepatitis which can be caused by a variety of distinct infectious agents. The spectrum of disease, which ranges from acute self-limited hepatitis to liver cirrhosis, not only reflects the different biological properties and pathogenicity of the hepatitis viruses, but is also the result of the specific interaction between each virus and

  4. Viral hepatitis in the Arctic

    Microsoft Academic Search

    Brian J McMahon

    Objectives. Summarize research on viral hepatitis in indigenous populations in the Arctic. Study De- sign. Literature review. Methods. Medline search from 1966-2003. Results. High prevalence rates of total hepatitis A antibody of > 50% and of hepatitis B of between 22% in Alaska and 42% in Greenland for total infection and between 3% in Canada and 12% in Siberia for

  5. Protective Effect of Brazilian Propolis against Liver Damage with Cholestasis in Rats Treated with ?-Naphthylisothiocyanate

    PubMed Central

    Nakamura, Tadashi; Ohta, Yoshiji; Ohashi, Koji; Ikeno, Kumiko; Watanabe, Rie; Tokunaga, Kenji; Harada, Nobuhiro

    2013-01-01

    We examined the protective effect of Brazilian propolis against liver damage with cholestasis in rats treated with ?-naphthylisothiocyanate (ANIT) in comparison with that of vitamin E (VE). Rats orally received Brazilian propolis ethanol extract (BPEE) (25, 50, or 100?mg/kg), VE (250?mg/kg) or vehicle at 12?h after intraperitoneal injection of ANIT (75?mg/kg) and were killed 24?h after the injection. Vehicle-treated rats showed liver cell damage and cholestasis, judging from the levels of serum marker enzymes and components. The vehicle group had increased serum total cholesterol, triglyceride, phospholipid, and lipid peroxide levels, increased hepatic lipid peroxide, reduced glutathione, and ascorbic acid levels and myeloperoxidase activity, and decreased hepatic superoxide dismutase activity. BPEE (50?mg/kg) administered to ANIT-treated rats prevented liver cell damage and cholestasis and attenuated these serum and hepatic biochemical changes except hepatic ascorbic acid, although administered BPEE (25 or 100?mg/kg) was less effective. VE administered to ANIT-treated rats prevented liver cell damage, but not cholestasis, and attenuated increased serum lipid peroxide level, increased hepatic lipid peroxide level and myeloperoxidase activity, and decreased hepatic superoxide dismutase activity. These results indicate that BPEE protects against ANIT-induced liver damage with cholestasis in rats more effectively than VE. PMID:23710219

  6. [Effect of notoginseng extracts and their components on lipopolysaccharide and galactosamine mixture-induced impaired hepatic function in mice].

    PubMed

    Komatsu, Ken-ichi; Tanaka, Hiroko; Nakagawa, Daisuke; Kawashima, Keiko

    2012-01-01

    The protective effects of notoginseng against hepatic damage were investigated in mice. To prepare a model animal of hepatitis, a mixture of lipopolysaccharide and galactosamine (LPS/GAlN) was administered intraperitoneally, leading to the impairment of hepatic function. Extracts of notoginseng or its components (ginsenoside Rb1 and ginsenoside Rg1) were orally administered 2 h before LPS/GalN injection. Eight hours after LPS/GalN injection, blood and liver tissue samples were collected. The levels of serum aspartate amino transferase (AST), alanine aminotransferase (ALT), tumor necrosis factor (TNF)-?, and interferon (IFN)-? were measured using commercial assay kits. Histologic changes in the tissue samples were also observed after hematoxylin-eosin staining. LPS/GalN administration increased the serum levels of AST and ALT, and histologic changes were noted, indicating hepatic cell damage. Prior to the increase in ALT, the serum levels of TNF-? and IFN-? were elevated after LPS/GalN injection. Pretreatment of the mice with either notoginseng extract or gensenoside Rb1 and Rg1 attenuated the LPS/GalN-induced hepatic damage markedly. The protective effects of the components against hepatic damage appeared to be less potent than those of the crude extract and prescription of notoginseng. Notoginseng may be clinically useful in patients with hepatitis. PMID:22790029

  7. Juvenile autoimmune hepatitis: Spectrum of the disease

    PubMed Central

    Maggiore, Giuseppe; Nastasio, Silvia; Sciveres, Marco

    2014-01-01

    Juvenile autoimmune hepatitis (JAIH) is a progressive inflammatory liver disease, affecting mainly young girls, from infancy to late adolescence, characterized by active liver damage, as shown by high serum activity of aminotransferases, by elevated immunoglobulin G levels, high titers of serum non organ-specific and organ-specific autoantibodies, and by interface hepatitis on liver biopsy. It is a multifactorial disease of unknown etiology in which environmental factors act as a trigger in genetically predisposed individuals. Two types of JAIH are identified according to the autoantibody panel detected at diagnosis: AIH-1, characterized by the presence of anti-smooth muscle antibody and/or antinuclear antibody and AIH-2, by anti-liver-kidney microsomal antibody type 1 and/or by the presence of anti-liver cytosol type 1 antibody. Epidemiological distribution, genetic markers, clinical presentation and pattern of serum cytokines differentiate the two types of AIH suggesting possible pathogenetic mechanisms. The most effective therapy for AIH is pharmacological suppression of the immune response. Treatment should be started as soon as the diagnosis is made to avoid severe liver damage and progression of fibrosis. The aim of this review is to outline the most significant and peculiar features of JAIH, based largely on our own personal database and on a review of current literature. PMID:25067998

  8. 72 FR 44560 - Guidance for Industry: Adequate and Appropriate Donor Screening Tests for Hepatitis B; Hepatitis...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2007-08-08

    ...Adequate and Appropriate Donor Screening Tests for Hepatitis B; Hepatitis B Surface Antigen Assays Used to Test Donors of Whole...Adequate and Appropriate Donor Screening Tests for Hepatitis B; Hepatitis B Surface Antigen (HBsAg)...

  9. Cutaneous manifestations of viral hepatitis.

    PubMed

    Akhter, Ahmed; Said, Adnan

    2015-02-01

    There are several extrahepatic cutaneous manifestations associated with hepatitis B and hepatitis C virus infection. Serum sickness and polyarteritis nodosa are predominantly associated with hepatitis B infection, whereas mixed cryoglobulinemia associated vasculitis and porphyria cutanea tarda are more frequently seen in hepatitis C infection. The clinico-pathogenic associations of these skin conditions are not completely defined but appear to involve activation of the host immune system including the complement system. Management of the aforementioned cutaneous manifestations of viral hepatitis is often similar to that done in cases without viral hepatitis, with control of immune activation being a key strategy. In cases associated with hepatitis B and C, control of viral replication with specific antiviral therapy is also important and associated with improvement in most of the associated clinical manifestations. PMID:25809574

  10. NK cells in chronic hepatitis C and hepatitis B Fine Characterization of Intra-hepatic NK cells Expressing

    E-print Network

    Boyer, Edmond

    1 NK cells in chronic hepatitis C and hepatitis B Fine Characterization of Intra-hepatic NK cells Expressing Natural Killer Receptors in Chronic Hepatitis B and C Paula Bonorino1,2* , Muhammad Ramzan 1. The proportions of intra-hepatic NK cells expressing either NKG2A, and/or CD158a,h, CD158b,j differed

  11. P. Roingeard -Journal of Viral Hepatitis 2013 ; 20, 77-84. Page 1 Hepatitis C virus diversity and hepatic steatosis

    E-print Network

    Paris-Sud XI, Université de

    P. Roingeard - Journal of Viral Hepatitis 2013 ; 20, 77-84. Page 1 REVIEW Hepatitis C virus diversity and hepatic steatosis P. Roingeard. INSERM U966, Université François Rabelais & CHRU de Tours, 10, published in "Journal of Viral Hepatitis 2013;20(2):77-84" #12;P. Roingeard - Journal of Viral Hepatitis

  12. Extracellular adenosine controls NKT-cell-dependent hepatitis induction.

    PubMed

    Subramanian, Meenakshi; Kini, Radhika; Madasu, Manasa; Ohta, Akiko; Nowak, Michael; Exley, Mark; Sitkovsky, Michail; Ohta, Akio

    2014-04-01

    Extracellular adenosine regulates inflammatory responses via the A2A adenosine receptor (A2AR). A2AR deficiency results in much exaggerated acute hepatitis, indicating nonredundancy of adenosine-A2AR pathway in inhibiting immune activation. To identify a critical target of immunoregulatory effect of extracellular adenosine, we focused on NKT cells, which play an indispensable role in hepatitis. An A2AR agonist abolished NKT-cell-dependent induction of acute hepatitis by concanavalin A (Con A) or ?-galactosylceramide in mice, corresponding to downregulation of activation markers and cytokines in NKT cells and of NK-cell co-activation. These results show that A2AR signaling can downregulate NKT-cell activation and suppress NKT-cell-triggered inflammatory responses. Next, we hypothesized that NKT cells might be under physiological control of the adenosine-A2AR pathway. Indeed, both Con A and ?-galactosylceramide induced more severe hepatitis in A2AR-deficient mice than in WT controls. Transfer of A2AR-deficient NKT cells into A2AR-expressing recipients resulted in exaggeration of Con A-induced liver damage, suggesting that NKT-cell activation is controlled by endogenous adenosine via A2AR, and this physiological regulatory mechanism of NKT cells is critical in the control of tissue-damaging inflammation. The current study suggests the possibility to manipulate NKT-cell activity in inflammatory disorders through intervention to the adenosine-A2AR pathway. PMID:24448964

  13. Hepatic resection with an Nd:YAG laser in pig.

    PubMed

    Godlewski, G; Ginoves, P; Chincholles, J M; Viel, E; Bureau, J P; Rouy, S; Mion, H; Dubois, A; Fesquet, J

    1983-01-01

    Eleven hepatic resections were performed by means of a divergent Nd:YAG laser. The beam was transmitted through a fiberoptic delivery system without any handpiece. The shortest resection time and most limited ischemic damage (4 mm) were obtained with 80-W power shoots and a low divergent beam (4 degrees 2 for full angle). The hemostatic effects of the Nd:YAG controlled bleeding from veins of up to 4.5 mm in diameter, and parenchymatic oozing from the cut edge minimized blood loss. Histological examination revealed the importance of cellular deterioration in the ischemic layer, while electron microscopy showed selective destruction of cell organelles and protein denaturation. Marked elevation of hepatic serum enzymes suggests a high degree of cellular damage. Postoperative examinations confirmed an uncomplicated healing process. Finally, the use of a flexible fiberoptic enables easy surgical manipulation. PMID:6668977

  14. Hepatic siderosis in alcoholics

    Microsoft Academic Search

    Andrew W. Jakobovits; Marsha Y. Morgan; Sheila Sherlock

    1979-01-01

    In a population of 157 (120 males, 37 females) predominantly British alcoholics with liver disease, the incidence of some degree of hepatic siderosis, as estimated by stainable parenchymal iron, was 57.3%. The incidence of significant siderosis (grades III and IV) was 7%, and was similar for both sexes. In the female alcoholics there was a significant correlation between age and

  15. Viral hepatitis in Bucharest.

    PubMed Central

    Paquet, C.; Babes, V. T.; Drucker, J.; Sénémaud, B.; Dobrescu, A.

    1993-01-01

    A seroprevalence survey of viral hepatitis was conducted in Bucharest, Romania, between April and July 1990 on a systematic sample of 1355 persons drawn from the general population and groups at higher risk of infection. Sera were tested for hepatitis A, B, and C (HAV, HBV and HCV, resp.) markers using an enzyme-linked immunosorbent assay (ELISA) method. The prevalences of HAV and HBV markers were high in all groups. A total of 47% of the adults from the general population and 39.8% of the children aged 0-16 years had at least one HBV marker. Of the pregnant women 7.8% were positive for hepatitis B surface antigen. Among infants (0-3 years of age) living in orphanages, the prevalence of at least one HBV marker was 54.6%. The findings also confirmed that HCV was circulating in Romania. The results are consistent with national surveillance data and confirm that viral hepatitis is a major public health problem in Romania. Preventive measures will have to include HBV immunization of infants, with an appropriately targeted immunization strategy being determined through further epidemiological studies. PMID:8313496

  16. Hepatitis (For Parents)

    MedlinePLUS

    ... have time to get any necessary immunizations. The HBV vaccine is given to both children and adults as ... cause the kind of response needed for a vaccine to be ... its own. Chronic hepatitis B can sometimes be treated using medications. Several drugs ...

  17. Foetal hepatic calcification.

    PubMed

    Hawass, N D; el Badawi, M G; Fatani, J A; al-Meshari, A; Makanjoula, D; Edress, Y B

    1990-01-01

    Thirty-three cases of 1,500 spontaneously-aborted foetuses showed hepatic calcifications. The exact location of these calcifications were confirmed by contrast studies, anatomic dissection, and further histology when necessary. Of them, 18 were calcified hepatic vein thrombi (CHVT), 12 were calcified portal vein thrombi (CPVT), 2 were parenchymal calcifications, and one was mixed. Associated anomalies were high (85% of cases). No significant difference was found between the type and percentage of anomalies of those with CHVT and those with CPVT. The most common anomalies encountered in all cases were meconium intraluminal calcification (27%), cystic hygroma (18%), and metaphyseal defect (18%). In view of this, it is suggested that a variety of severe foetal illnesses predispose to CHVT and CPVT. At correlation with maternal factors, it was found that the highest incidence was in the third decade. A significant high percentage of mothers (33%) had been on contraceptive pills, and there was interesting inverse relationship of hepatic calcification with gravidity. Practically, it is also hoped that the awareness of the presence of various types of hepatic calcifications will help in their detection prenatally by ultrasound. PMID:2216588

  18. Viral hepatitis B

    Microsoft Academic Search

    Ching Lung Lai; Vlad Ratziu; Man-Fung Yuen; Thierry Poynard

    2003-01-01

    More than 170 million people worldwide are chronically infected with the hepatitis C virus (HCV), which is responsible for more than 100 000 cases of liver cancer per year, with similar numbers of digestive haemorrhage and ascites episodes. Major breakthroughs have been made in diagnosis and treatment, and advances in molecular biology mean that the replicative state of the virus

  19. Induction of hepatitis by JNK-mediated expression of TNF?

    PubMed Central

    Das, Madhumita; Sabio, Guadalupe; Jiang, Feng; Rincón, Mercedes; Flavell, Richard A.; Davis, Roger J.

    2009-01-01

    The cJun NH2-terminal kinase (JNK) signaling pathway has been implicated in the development of tumor necrosis factor (TNF) -dependent hepatitis. Indeed, JNK may play a critical role in hepatocytes during TNF-stimulated cell death in vivo. To test this hypothesis, we examined the phenotype of mice with compound disruption of the Jnk1 and Jnk2 genes. Mice with loss of JNK1/2 expression in hepatocytes exhibited no defects in the development of hepatitis compared with control mice. In contrast, mice with loss of JNK1/2 in the hematopoietic compartment exhibited a profound defect in hepatitis that was associated with markedly reduced expression of TNF?. Together, these data indicate that JNK is required for TNF? expression, but JNK is not required for TNF?-stimulated death of hepatocytes. Indeed, TNF?-induced similar hepatic damage in mice with hepatocyte-specific JNK1/2-deficiency and control mice. These observations confirm a role for JNK in the development of hepatitis, but identify hematopoietic cells as the site of the essential function of JNK. PMID:19167327

  20. The concanavalin A model of acute hepatitis in mice.

    PubMed

    Heymann, F; Hamesch, K; Weiskirchen, R; Tacke, F

    2015-04-01

    The intravenous injection of the plant lectin concanavalin A (ConA) is a widely used model for acute immune-mediated hepatitis in mice. In contrast to several other models for acute hepatic damage, ConA-induced injury is primarily driven by the activation and recruitment of T cells to the liver. Hence, the ConA model has unique features with respect to its pathogenesis and important similarities to immune-mediated hepatitis in humans, such as autoimmune hepatitis, acute viral hepatitis or distinct entities of drug toxicity leading to immune activation. However, the ConA model has considerable variability, depending on the preparation of the compound, genetic background of the mice, sex, age and microbial environment of the animal facility barrier. This standard operating procedure (SOP) comprises a detailed protocol for the ConA application, including preparation of ConA working solution, handling of the animals, choice of the appropriate conditions and endpoints, as well as efficient dose-finding. PMID:25835734

  1. Hepatitis B and human immunodeficiency virus co-infection.

    PubMed

    Phung, Bao-Chau; Sogni, Philippe; Launay, Odile

    2014-12-14

    Hepatitis B and human immunodeficiency virus (HBV and HIV) infection share transmission patterns and risk factors, which explains high prevalence of chronic HBV infection in HIV infected patients. The natural course of HBV disease is altered by the HIV infection with less chance to clear acute HBV infection, faster progression to cirrhosis and higher risk of liver-related death in HIV-HBV co-infected patients than in HBV mono-infected ones. HIV infected patients with chronic hepatitis B should be counseled for liver damage and surveillance of chronic hepatitis B should be performed to screen early hepatocellular carcinoma. Noninvasive tools are now available to evaluate liver fibrosis. Isolated hepatitis B core antibodies (anti-HBc) are a good predictive marker of occult HBV infection. Still the prevalence and significance of occult HBV infection is controversial, but its screening may be important in the management of antiretroviral therapy. Vaccination against HBV infection is recommended in non-immune HIV patients. The optimal treatment for almost all HIV-HBV co-infected patients should contain tenofovir plus lamivudine or emtricitabine and treatment should not be stopped to avoid HBV reactivation. Long term tenofovir therapy may lead to significant decline in hepatitis B surface Antigen. The emergence of resistant HBV strains may compromise the HBV therapy and vaccine therapy. PMID:25516647

  2. Durchbruch bei der Therapie der Hepatitis C

    E-print Network

    Manstein, Dietmar J.

    Durchbruch bei der Therapie der Hepatitis C: Segen für die Patienten ­ Albtraum für die Behandler -Virushepatitis Oktober 2012 #12;H. Wedemeyer -Virushepatitis Oktober 2012 Hepatitisviren Hepatitis A Feinstone 1973 RNA Hepatitis B Blumberg 1965 DNA Hepatitis C Houghton 1988 RNA Hepatitis D Rizzetto 1977 RNA

  3. The Impact of Hepatic Steatosis on Hepatic Ischemia-Reperfusion Injury in Experimental Studies: A Systematic Review

    PubMed Central

    Chu, Michael J. J.; Hickey, Anthony J. R.; Phillips, Anthony R. J.; Bartlett, Adam S. J. R.

    2013-01-01

    Background. The impact of hepatic steatosis on outcome following hepatic ischemia-reperfusion injury (IRI) remains controversial with conflicting clinical results. A number of experimental studies have been published examining the relationship between hepatic steatosis and IRI. This systematic review evaluates these experimental studies. Methods. An electronic search of the Medline and Embase databases (January 1946 to June 2012) was performed to identify studies that reported relevant outcomes in animal models of hepatic steatosis subjected to IRI. Results. A total of 1314 articles were identified, of which 33 met the predefined criteria and were included in the study. There was large variation in the type of animal model, duration, and type of IRI and reporting of histological findings. Increased macrovesicular steatosis (>30%) was associated with increased histological damage, liver function derangement, and reduced survival. Increased duration of warm or cold ischemia had a negative impact on all outcomes measured. Microvesicular steatosis did not influence outcome. Conclusions. Findings from this systemic review support the hypothesis that livers with >30% macrovesicular steatosis are less tolerant of IRI. Clinically, it is likely that these findings are applicable to patients undergoing hepatic resection, but further studies are required to confirm these data. PMID:24062999

  4. The Effect of p38 Mitogen-Activated Protein Kinase Activation on Inflammatory Liver Damage following Hemorrhagic Shock in Rats

    PubMed Central

    Sato, Hiroaki; Tanaka, Toshiko; Tanaka, Noriyuki

    2012-01-01

    Hemorrhagic shock is a frequent cause of liver failure and often leads to a fatal outcome. Several studies have revealed that p38 MAPK is a key mediator in hemorrhagic damage of the primary organs through the activation of proinflammatory cytokines such as tumor necrosis factor (TNF)-? and interleukin (IL)-1?. However, the precise role of these factors in liver damage following hemorrhagic shock is unclear. In this study, we used FR167653, a specific inhibitor of p38 MAPK phosphorylation, to examine the role of p38 MAPK in liver damage occurring up to 5 hours after a hemorrhagic episode in a rat model. Activation of p38 MAPK in the liver as well as an increase in hepatic mRNA expression and serum concentrations of TNF-? and IL-1? occurred during the early phase after hemorrhage. Increased serum levels of hepatic enzymes, as well as histological damage and activated neutrophil accumulation in the liver, were observed in the late phase following hemorrhagic shock. FR167653 inhibited the inflammation-related hepatic injury following hemorrhagic shock. Bacterial lipopolysaccharide (LPS) derived from the gut appeared to have little effects on the hepatic damage. These results demonstrate that p38 MAPK activation is induced by hepatic ischemia during hemorrhagic shock and plays an important role both in the hepatic expression of proinflammatory cytokines and in the development of inflammation-related liver damage. PMID:22253904

  5. Liver Damage due to Methotrexate in Patients with Psoriasis

    PubMed Central

    Dahi, M. G. C.; Gregory, M. M.; Scheuer, P. J.

    1971-01-01

    Liver function and histological changes in liver biopsies were studied in 37 patients who had been treated for psoriasis with methotrexate. Cirrhosis was found in seven (19%) and hepatic fibrosis of varying severity in 10 (27%). Minor abnormalities in another 17 (46%) consisted of fatty change, round cell infiltration, and extensive vacuolation of liver cell nuclei. In only three (8%) was hepatic histology entirely normal. The severity of liver damage was related to the duration of methotrexate treatment. Minor abnormalities of liver function tests and liver histology were also found in eight control psoriatic patients. Standard liver function tests were of little value in predicting the degree of liver damage. It appears that methotrexate, in the doses normally used to control psoriasis, may cause cirrhosis if treatment is prolonged and that liver biopsy is necessary for evaluation of liver damage in these patients. ImagesFIG. 2FIG. 3FIG. 4FIG. 5 PMID:5548839

  6. Damaged Skylab

    NASA Technical Reports Server (NTRS)

    1973-01-01

    The Saturn V vehicle, carrying the unmarned orbital workshop for the Skylab-1 mission, lifted off successfully and all systems performed normally. Sixty-three seconds into the flight, engineers in the operation support and control center saw an unexpected telemetry indication that signalled that damages occurred on one solar array and the micrometeoroid shield during the launch. The micrometeoroid shield, a thin protective cylinder surrounding the workshop, that protected it from tiny space particles and the sun's scorching heat, ripped loose from its position around the workshop. This caused the loss of one solar wing and jammed the other. Still unoccupied, the Skylab was stricken with the loss of the heat shield and sunlight beat mercilessly on the lab's sensitive skin. Internal temperatures soared, rendering the station uninhabitable, threatening foods, medicines, films, and experiments. This image, taken during a fly-around inspection by the Skylab-2 crew, shows the exterior skin of the workshop discolored by solar radiation. The Marshall Space Flight Center (MSFC) developed, tested, rehearsed, and approved three repair options. These options included a parasol sunshade and a twin-pole sunshade to restore the temperature inside the workshop, and a set of metal cutting tools to free the jammed solar panel.

  7. Management of Covert Hepatic Encephalopathy

    PubMed Central

    Waghray, Abhijeet; Waghray, Nisheet; Mullen, Kevin

    2014-01-01

    Hepatic encephalopathy is a reversible progressive neuropsychiatric disorder that encompasses a wide clinical spectrum. Covert hepatic encephalopathy is defined as patients with minimal hepatic encephalopathy and Grade I encephalopathy by West-Haven Criteria. Terminology such as “sub-clinical”, “latent”, and “minimal” appear to trivialize the disease and have been replaced by the term covert. The lack of clinical signs means that covert hepatic encephalopathy is rarely recognized or treated outside of clinical trials with options for therapy based on patients with episodic hepatic encephalopathy. This review discusses the current available options for therapy in covert hepatic encephalopathy and focuses on non-absorbable disacharides (lactulose or lactitol), antibiotics (rifaximin), probiotics/synbiotics and l-ornithine-l-aspartate.

  8. Occult hepatitis B in Cuban HIV patients.

    PubMed

    Marité, Bello; Montalvo, María Caridad; Rodríguez, Licel de Los Ángeles; Sariego, Susel; Verdasquera, Denis; Vincent, Marguerite; Gutiérrez, Aidonis; Sánchez, Meilin

    2011-04-01

    INTRODUCTION Co-infections between hepatitis B and HIV viruses are frequent due to their similar epidemiological characteristics. Worldwide, hepatitis B infection is one of the main causes of hepatocellular carcinoma and cirrhosis. In Cuba as elsewhere, prevalences of hepatitis B and hepatitis C viral infections are higher in persons with HIV. These hepatitis viruses act as opportunistic infections in persons with HIV. In other contexts, persons with HIV have been found to be at higher risk for occult hepatitis B, defined as the presence in serum or plasma of hepatitis B virus DNA and antibodies to its core antigen, in the absence of hepatitis B surface antigen. OBJECTIVES Describe occult hepatitis B prevalence in Cuban HIV-positive patients and explore possible associations with their clinical characteristics. METHODS A total of 325 serum samples from patients positive for HIV and negative for hepatitis B surface antigen were studied, divided into two groups, Group 1, negative for hepatitis C virus; and Group 2, positive for hepatitis C virus. Exposure to hepatitis B was determined by testing for hepatitis B core antigen; samples positive for hepatitis B core antigen were then examined for presence of antibodies to hepatitis B surface antigen. Both determinations were done by ultramicroELISA. In samples positive for hepatitis B core antigen with levels of antibodies to hepatitis B surface antigen of <50 IU/L, real-time polymerase chain reaction was used to detect hepatitis B DNA and its presence examined in relation to several clinical variables. All data were obtained from patients' clinical records. RESULTS In the hepatitis-C-negative group, 27.9% (68/243) of serum samples tested were positive for hepatitis B core antigen. In the hepatitis-C-positive group, 37.8% (31/82) were positive for hepatitis B core antigen. Total hepatitis B virus exposure prevalence was 30.4% (99/325); 54.5% (54/99) showing low immunity (hepatitis B virus surface antigen <50 IU/L) and 24% of these (13/54), occult hepatitis. There was no statistically significant association between hepatitis B virus DNA and any of the clinical variables studied. CONCLUSIONS Low-immunity HIV-positive persons in our study were exposed to hepatitis B virus. Diagnosis of occult hepatitis B infection is frequent in these patients. This study suggests that diagnostic protocols for persons with HIV and without hepatitis B surface antigen should include testing for hepatitis B core antigen, with positive results followed by molecular techniques to detect occult hepatitis B. This study makes a useful contribution to prevention and control of hepatitis B in Cuba. PMID:21654589

  9. Primary hepatic sarcomas: CT findings

    Microsoft Academic Search

    Ri-Sheng Yu; Ying Chen; Biao Jiang; Liu-Hong Wang; Xiu-Fang Xu

    2008-01-01

    Primary hepatic sarcomas are rare tumors that are difficult to diagnose clinically. Different primary hepatic sarcomas may\\u000a have different clinical, morphologic, and radiological features. In this pictorial review, we summarized computed tomography\\u000a (CT) findings of some relatively common types of hepatic sarcomas, including angiosarcoma, epithelioid hemangioendothelioma\\u000a (EHE), liposarcoma, undifferentiated embryonal sarcoma (UES), leiomyosarcoma, malignant fibrous histiocytoma (MFH), and carcinosarcoma\\u000a (including

  10. Clotiazepam-induced acute hepatitis.

    PubMed

    Habersetzer, F; Larrey, D; Babany, G; Degott, C; Corbic, M; Pessayre, D; Benhamou, J P

    1989-09-01

    We report the case of a patient who developed acute hepatitis with extensive hepatocellular necrosis, 7 months after the onset of administration of clotiazepam, a thienodiazepine derivative. Clotiazepam withdrawal was followed by prompt recovery. The administration of several benzodiazepines, chemically related to clotiazepam, did not interfere with recovery and did not induce any relapse of hepatitis. This observation shows that clotiazepam can induce acute hepatitis and suggests that there is no cross hepatotoxicity between clotiazepam and several benzodiazepines. PMID:2572625

  11. Acute viral hepatitis in Hanoi, Viet Nam

    Microsoft Academic Search

    A. L. Corwin; T. C. Dai; Dao Dinh Duc; P. I. Suu; Nguyen Thu Van; Le Dang Ha; M. Janick; L. Kanti; Anni Sie; R. Soderquist; R. Graham; S. F. Wignall; K. C. Hyams

    1996-01-01

    A study of acute hepatitis was conducted in Hanoi, Viet Nam, from January 1993 to February 1995; 188 sera from clinical hepatitis cases were screened by enzyme-linked immunosorbent assay for immunoglobulin (Ig) M anti-hepatitis A virus (HAV), IgM anti-hepatitis B core antigen (HBc), IgG anti-hepatitis C virus (HCV), IgG anti-hepatitis E virus (HEV) and IgM anti-HEV. Additionally, 187 sera from

  12. Hepatitis E: current status.

    PubMed

    Pérez-Gracia, María Teresa; Mateos Lindemann, María Luísa; Caridad Montalvo Villalba, María

    2013-11-01

    Acute hepatitis E is a very common disease in developing countries, to the point that, according to World Health Organization estimates, one third of the world's population has been exposed to HEV. It also causes outbreaks in refugee camps or after natural disasters such as floods or earthquakes. Sporadic cases of acute hepatitis have been observed in practically all European countries and other developed geographical areas, not only in travelers from endemic countries but also in people with no risk factors. But, lately, new aspects of this infection are appearing in industrialized countries such as the possibility of the disease becoming chronic in transplant patients, the immunocompromised in general, and even in patients with previous liver disease who are immunocompetent. In this comprehensive review, we summarize the current knowledge on HEV infection. PMID:24038432

  13. Chronic hepatitis C

    Microsoft Academic Search

    Tram T. Tran; Paul Martin

    2001-01-01

    Opinion statement  Infection with hepatitis C virus (HCV) accounts for 40% of cases of chronic liver disease in the United States and is now\\u000a the most common indication for liver transplantation. Estimates suggest that 4 million people (1.8%) of the American population\\u000a are or have been infected with HCV. Currently, the treatment of choice for patients with chronic HCV infection is

  14. Hepatitis C in veterans

    Microsoft Academic Search

    Edmund J. Bini

    2003-01-01

    Hepatitis C virus (HCV) infection is the most common chronic bloodborne infection in the United States and has recently been\\u000a identified as the single most important emerging pathogen in the Department of Veterans Affairs (VA) health care system. The\\u000a Third National Health and Nutrition Examination Survey estimated that 3.9 million Americans (1.8%) are infected with HCV.\\u000a In contrast, the prevalence

  15. Hepatitis E Virus Infection

    PubMed Central

    Dalton, Harry R.; Abravanel, Florence; Izopet, Jacques

    2014-01-01

    SUMMARY Hepatitis E virus (HEV) infection is a worldwide disease. An improved understanding of the natural history of HEV infection has been achieved within the last decade. Several reservoirs and transmission modes have been identified. Hepatitis E is an underdiagnosed disease, in part due to the use of serological assays with low sensitivity. However, diagnostic tools, including nucleic acid-based tests, have been improved. The epidemiology and clinical features of hepatitis E differ between developing and developed countries. HEV infection is usually an acute self-limiting disease, but in developed countries it causes chronic infection with rapidly progressive cirrhosis in organ transplant recipients, patients with hematological malignancy requiring chemotherapy, and individuals with HIV. HEV also causes extrahepatic manifestations, including a number of neurological syndromes and renal injury. Acute infection usually requires no treatment, but chronic infection should be treated by reducing immunosuppression in transplant patients and/or the use of antiviral therapy. In this comprehensive review, we summarize the current knowledge about the virus itself, as well as the epidemiology, diagnostics, natural history, and management of HEV infection in developing and developed countries. PMID:24396139

  16. Hepatitis - Multiple Languages: MedlinePlus

    MedlinePLUS

    ... ?????? ????? ???????? - ??????? Bilingual PDF Health Information Translations Chinese - Simplified (????) Viral Hepatitis ????? - ???? (Chinese - Simplified) Bilingual PDF Health Information Translations Chinese - Traditional (????) Viral Hepatitis ????? - ???? (Chinese - ...

  17. Radioembolization of hepatic tumors.

    PubMed

    Kennedy, Andrew

    2014-06-01

    Unresectable primary and metastatic liver tumors are a leading cause of cancer mortality and morbidity. This remains a challenging and key task for every oncologist despite significant advances that have been made with selective targeted systemic agents and in technology advances with radiotherapy delivery. Radioembolization (RE) is a technique of permanently implanting microspheres containing Yttrium-90 ((90)Y), a beta-emitting isotope with a treatment range of 2 mm, into hepatic tumors. This form of brachytherapy utilizes the unique dual vascular anatomy of the liver to preferentially deliver radioactive particles via the hepatic artery to tumor, sparing normal liver parenchyma. The main treatment inclusion criteria are patients with solid tumors, compensated liver functions, life expectancy of at least three months, and ECOG performance status 0-2. Benefit of RE has been proven in patients that have low-to-moderate extrahepatic disease burden, prior liver radiotherapy, heavy prior chemotherapy and biologic agent exposure, and history of hepatic surgery or ablation. Most of the clinical evidence is reported in metastatic colorectal, and neuroendocrine tumors (NET), and primary hepatocellular cancer. A growing body of data supports the use of RE in hepatic metastatic breast cancer, intrahepatic cholangiocarinoma, and many other metastatic tumor types. Side effects are typically mild constitutional and GI issues limited to the first 7-14 days post treatment, with only 6% grade 3 toxicity reported in large series. Potentially serious or fatal radiation induced liver disease is extremely rare, reported in only 1% or fewer in major series of both metastatic and primary tumors treated with RE. Currently, high priority prospective clinical trials are testing RE combined with chemotherapy in first line therapy for colorectal hepatic metastases, and combined with sorafenib for hepatocellular carcinomas (HCCs). Fortunately, this beneficial and now widely available therapy is being increasingly incorporated into the standard therapy algorithms of multidisciplinary GI cancer teams worldwide. This form of radiotherapy differs significantly from daily external beam radiotherapy in many ways, particularly in dose rate, dosimetric coverage and duration of radiation delivery, side effects, and patient selection factors. A wealth of experience using RE in solid tumors exists and ongoing major prospective clinical trials will soon clarify the role of RE in the management of metastatic colorectal liver metastases. PMID:24982766

  18. Immunology of hepatitis B virus and hepatitis C virus infection

    Microsoft Academic Search

    Michelina Nascimbeni; Barbara Rehermann

    2005-01-01

    More than 500 million people worldwide are persistently infected with the hepatitis B virus (HBV) and\\/or hepatitis C virus (HCV) and are at risk of developing chronic liver disease, cirrhosis and hepatocellular carcinoma. Despite many common features in the pathogenesis of HBV- and HCV-related liver disease, these viruses markedly differ in their virological properties and in their immune escape and

  19. CT in hepatic cirrhosis and chronic hepatitis.

    PubMed

    Valls, Carlos; Andía, Eduard; Roca, Yolanda; Cos, Mònica; Figueras, Juan

    2002-02-01

    Cirrhosis is a diffuse liver disease with premalignant potential in which hepatocellular carcinoma (HCC) frequently develops. The hemodynamics of contrast material are the key to diagnosis of focal liver lesions with computed tomography (CT). Lesions with arterial-dominant vascularity, such as HCC, show brisk enhancement during the arterial phase, whereas lesions with portal blood supply can appear as hyperenhancing lesions in the portal phase. The advent of helical CT has significantly improved the CT examination of the liver because the arterial phase can be displayed independently of the portal phase. The addition of arterial phase imaging to conventional portal phase imaging seems to improve tumor detection and characterization. Although HCC is the single most frequent tumor seen in chronic liver disease, other lesions such as peripheral cholangiocarcinoma and hemangioma should be considered in the differential diagnosis. Optimization of helical CT techniques may allow better detection and characterization of these lesions. In addition to tumor detection, CT plays an important role in preoperative staging of HCC as well as in preoperative assessment of patient candidates to hepatic transplantation. The use of CT angiography with maximum intensity projection techniques may allow for better preoperative work-up and vascular mapping in HCC patients. This article shows the spectrum of helical CT findings in chronic liver disease and specifically in the imaging of HCC and other focal lesions. PMID:11866222

  20. Methamphetamine causes acute hyperthermia-dependent liver damage.

    PubMed

    Halpin, Laura E; Gunning, William T; Yamamoto, Bryan K

    2013-10-01

    Methamphetamine-induced neurotoxicity has been correlated with damage to the liver but this damage has not been extensively characterized. Moreover, the mechanism by which the drug contributes to liver damage is unknown. This study characterizes the hepatocellular toxicity of methamphetamine and examines if hyperthermia contributes to this liver damage. Livers from methamphetamine-treated rats were examined using electron microscopy and hematoxylin and eosin staining. Methamphetamine increased glycogen stores, mitochondrial aggregation, microvesicular lipid, and hydropic change. These changes were diffuse throughout the hepatic lobule, as evidenced by a lack of hematoxylin and eosin staining. To confirm if these changes were indicative of damage, serum aspartate and alanine aminotransferase were measured. The functional significance of methamphetamine-induced liver damage was also examined by measuring plasma ammonia. To examine the contribution of hyperthermia to this damage, methamphetamine-treated rats were cooled during and after drug treatment by cooling their external environment. Serum aspartate and alanine aminotransferase, as well as plasma ammonia were increased concurrently with these morphologic changes and were prevented when methamphetamine-induced hyperthermia was blocked. These findings support that methamphetamine produces changes in hepatocellular morphology and damage persisting for at least 24 h after drug exposure. At this same time point, methamphetamine treatment significantly increases plasma ammonia concentrations, consistent with impaired ammonia metabolism and functional liver damage. Methamphetamine-induced hyperthermia contributes significantly to the persistent liver damage and increases in peripheral ammonia produced by the drug. PMID:25505562

  1. Methamphetamine causes acute hyperthermia-dependent liver damage

    PubMed Central

    Halpin, Laura E; Gunning, William T; Yamamoto, Bryan K

    2013-01-01

    Methamphetamine-induced neurotoxicity has been correlated with damage to the liver but this damage has not been extensively characterized. Moreover, the mechanism by which the drug contributes to liver damage is unknown. This study characterizes the hepatocellular toxicity of methamphetamine and examines if hyperthermia contributes to this liver damage. Livers from methamphetamine-treated rats were examined using electron microscopy and hematoxylin and eosin staining. Methamphetamine increased glycogen stores, mitochondrial aggregation, microvesicular lipid, and hydropic change. These changes were diffuse throughout the hepatic lobule, as evidenced by a lack of hematoxylin and eosin staining. To confirm if these changes were indicative of damage, serum aspartate and alanine aminotransferase were measured. The functional significance of methamphetamine-induced liver damage was also examined by measuring plasma ammonia. To examine the contribution of hyperthermia to this damage, methamphetamine-treated rats were cooled during and after drug treatment by cooling their external environment. Serum aspartate and alanine aminotransferase, as well as plasma ammonia were increased concurrently with these morphologic changes and were prevented when methamphetamine-induced hyperthermia was blocked. These findings support that methamphetamine produces changes in hepatocellular morphology and damage persisting for at least 24 h after drug exposure. At this same time point, methamphetamine treatment significantly increases plasma ammonia concentrations, consistent with impaired ammonia metabolism and functional liver damage. Methamphetamine-induced hyperthermia contributes significantly to the persistent liver damage and increases in peripheral ammonia produced by the drug. PMID:25505562

  2. Protect Yourself against Hepatitis A and B: A Guide for Gay and Bisexual Men

    MedlinePLUS

    ... of hepatitis A vaccine. Will hepatitis A or hepatitis B vaccine protect me from hepatitis C? No. Hepatitis A, ... Australia should get vaccinated against hepatitis A virus. Hepatitis B vaccine is recommended for many travelers also. Discuss this ...

  3. Molecular biology of hepatitis B virus infection.

    PubMed

    Seeger, Christoph; Mason, William S

    2015-05-01

    Human hepatitis B virus (HBV) is the prototype of a family of small DNA viruses that productively infect hepatocytes, the major cell of the liver, and replicate by reverse transcription of a terminally redundant viral RNA, the pregenome. Upon infection, the circular, partially double-stranded virion DNA is converted in the nucleus to a covalently closed circular DNA (cccDNA) that assembles into a minichromosome, the template for viral mRNA synthesis. Infection of hepatocytes is non-cytopathic. Infection of the liver may be either transient (<6 months) or chronic and lifelong, depending on the ability of the host immune response to clear the infection. Chronic infections can cause immune-mediated liver damage progressing to cirrhosis and hepatocellular carcinoma (HCC). The mechanisms of carcinogenesis are unclear. Antiviral therapies with nucleoside analog inhibitors of viral DNA synthesis delay sequelae, but cannot cure HBV infections due to the persistence of cccDNA in hepatocytes. PMID:25759099

  4. Adaptive response in hepatitis B virus infection.

    PubMed

    Loggi, E; Gamal, N; Bihl, F; Bernardi, M; Andreone, P

    2014-05-01

    Hepatitis B virus (HBV) is a major cause of acute and chronic liver inflammation worldwide. The immune response against the virus represents a key factor in determining infection outcome, in terms of both viral clearance and the perpetuation of liver damage. Significant advances have recently been achieved regarding the functions of antiviral CD8+ T cells, leading to a better understanding of their abnormalities during chronic infection as well as the pathways to be manipulated to reverse the immune impairment of chronic infection. In this review, we aimed to analyse the patterns of adaptive immunity that develop during acute infection and the profiles in chronic infection. In addition to CD8+ T cells, which are the best-described subset to date, we reviewed and commented on the direct and indirect roles of CD4+ T cells and B cells. PMID:24674098

  5. Nonconvulsive status epilepticus disguising as hepatic encephalopathy

    PubMed Central

    Jo, Yong Min; Lee, Sung Wook; Han, Sang Young; Baek, Yang Hyun; Ahn, Ji Hye; Choi, Won Jong; Lee, Ji Young; Kim, Sang Ho; Yoon, Byeol A

    2015-01-01

    Nonconvulsive status epilepticus has become an important issue in modern neurology and epileptology. This is based on difficulty in definitively elucidating the condition and its various clinical phenomena and on our inadequate insight into the intrinsic pathophysiological processes. Despite nonconvulsive status epilepticus being a situation that requires immediate treatment, this disorder may not be appreciated as the cause of mental status impairment. Although the pathophysiology of nonconvulsive status epilepticus remains unknown, this disorder is thought to lead to neuronal damage, so its identification and treatment are important. Nonconvulsive status epilepticus should be considered in the differential diagnosis of patients with liver cirrhosis presenting an altered mental status. We report a case of a 52-year-old male with liver cirrhosis presenting an altered mental status. He was initially diagnosed with hepatic encephalopathy but ultimately diagnosed with nonconvulsive status epilepticus by electroencephalogram. PMID:25945028

  6. Hepatitis C Virus and Cardiomyopathy

    Microsoft Academic Search

    Akira Matsumori

    2000-01-01

    The importance of hepatitis C virus infection has been recently noted in patients with hypertrophic cardiomyopathy or dilated cardiomyopathy. In a collaborative research project of the Committees for the Study of Idiopathic Cardiomyopathy, hepatitis C virus antibody was found in 74 of 697 patients (10.65) with hypertrophic cardiomyopathy and in 42 of 663 patients (6.3%) with dilated cardiomyopathy; these prevalences

  7. Adaptive Immunity in Autoimmune Hepatitis

    Microsoft Academic Search

    Maria Serena Longhi; Yun Ma; Giorgina Mieli-Vergani; Diego Vergani

    2010-01-01

    The histological lesion of interface hepatitis, with its dense portal cell infiltrate consisting of lymphocytes, monocytes\\/macrophages and plasma cells, was the first to suggest an autoaggressive cellular immune attack in the pathogenesis of autoimmune hepatitis (AIH). Immunohistochemical studies, focused on the phenotype of inflammatory cells infiltrating the liver parenchyma, have shown a predominance of ??-T cells. Amongst these cells, the

  8. Calpain and lipopolysaccharide mediated hepatitis

    E-print Network

    Rose, Robert Edward

    2009-06-02

    I INTRODUCTION?????????????????????? 1 II DEVELOPMENT OF THE NEUTROPHILIC HEPATITIS MODEL?... 5 Materials and Methods???????????????... 5 Results?????????????????????? 9 Discussion... II DEVELOPMENT OF THE NEUTROPHILIC HEPATITIS MODEL MATERIALS AND METHODS Animals and treatment All animal procedures were approved by the Texas A&M University Laboratory Animal Care Committee (ULACC) and conformed to the standards set forth...

  9. [Hepatitis in dogs; a review].

    PubMed

    Rothuizen, J; van den Ingh, T S

    1998-04-15

    As with most liver diseases, the symptoms of hepatitis in dogs are nearly always aspecific: the dogs eat less, are apathetic, sometimes have polyuria/polydipsia, and sometimes have diarrhoea. Hepatoencephalopathy and ascites only occur with these symptoms in very advanced stages of chronic hepatitis. Only a part of the dogs have jaundice. Because of these aspecific symptoms, the diagnosis hepatitis is often not taken into consideration, even though the presence of a liver disease can be easily detected by measuring plasma concentrations of alkaline phosphatase and bile acids, one or both of which are elevated. The diagnosis is confirmed by histological examination of a liver biopsy sample. The most common forms of hepatitis are non-specific reactive hepatitis, acute hepatitis, and chronic hepatitis. Non-specific reactive hepatitis is a reaction against endotoxin as a result of sepsis or an increased gastrointestinal absorption. Treatment is directed to the primary process. Leptospirosis also causes non-specific reactive hepatitis, but then renal insufficiency is the most prominent feature. The diagnosis is made not on the basis of a liver biopsy but on the basis of increased IgM titres against Leptospira. Immediate treatment with antibiotics and infusions at the first signs (jaundice and uraemia) can save the animal's life. Acute hepatitis can develop as a result of infection, toxins, or liver hypoxia. There is no specific treatment, but adequate recovery often occurs with supportive treatment. Corticosteroids are contraindicated. Chronic hepatitis, which can lead to cirrhosis, is the most common form of hepatitis. It is an autoimmune inflammatory reaction that is usually caused by a virus infection but sometimes by poisoning (intoxication). Long treatment with prednisolone or azathioprine is usually successful, but early recognition of the disease increases the likelihood of success. Nowadays, chronic hepatitis due to hepatic copper accumulation in Beddlington terriers can be detected by DNA tests. Such tests make it possible to distinguish between carriers and non-carriers. Affected animals can be kept symptom-free by life-long treatment with zinc gluconate or penicillamine. PMID:9584348

  10. Pathological Role of Interleukin-17 in Poly I:C-Induced Hepatitis

    PubMed Central

    He, Jianqin; Lang, Guanjing; Ding, Shiping; Li, Lanjuan

    2013-01-01

    Immune-mediated responses were the main causes of liver damage during viral hepatitis, and recently viral RNA mimetic Poly I:C was used to induce a NK cell-dominated acute hepatitis. Interleukin-17A (IL-17A), the cytokine tightly associated with various autoimmune diseases, was known to play protective or pathological roles in LPS and ConA-induced hepatitis. However, its role in NK cell-mediated acute hepatitis remains unknown. Here we demonstrated that Poly I:C treatment triggered IL-17A production from hepatic ??T cells. Neutralizing IL-17A by monoclonal antibodies reduced Poly I:C-induced intrahepatic inflammatory responses and the liver injury through decreased accumulation, activation and cytolytic activity of NK cells in the liver. Furthermore, Poly I:C didn't trigger IL-17A secretion from ??T cells directly, and Kuppfer cells were demonstrated to be the accessory cell that can secrete IL-23. Finally, our findings demonstrated a pathological role of IL-17A and ??T cells in Poly I:C-induced acute hepatitis, which provides novel insights into viral infection-induced hepatitis and may serve as potential target in clinic immunotherapy against these disease. PMID:24069246

  11. Hepatitis B Vaccines

    Microsoft Academic Search

    Oren Shibolet; Daniel Shouval

    \\u000a Key Principles\\u000a \\u000a Initial immunization strategies against hepatitis B virus (HBV) infection concentrated on high-risk groups. This strategy,\\u000a which was successful in individual situations, failed to reduce the incidence and prevalence of HBV in the general population.\\u000a \\u000a \\u000a \\u000a As a result, in 1991 the World Health Organization (WHO) has recommended that HBV universal immunization should be integrated\\u000a into national immunization programs in

  12. Hepatic visceral larva migrans

    PubMed Central

    Rohilla, Seema; Jain, Nitin; Yadav, Rohtas; Dhaulakhandi, Dhara Ballabh

    2013-01-01

    Visceral larva migrans (VLM) is a systemic manifestation of migration of second stage larvae of nematodes through the tissue of human viscera. It is not uncommon but is underdiagnosed in developing countries. The liver is the most common organ to be involved due to its portal venous blood supply. The imaging findings are subtle and differentiation from hepatocellular carcinoma (HCC), metastases, cystic mesenchymal hamartoma and granulomatous diseases is difficult. This case report highlights the imaging features of hepatic lesions of VLM along with clinical and laboratory data which help in clinching the diagnosis. PMID:23853189

  13. Hepatic alveolar echinococcosis.

    PubMed

    Farrokh, Donya; Zandi, Behrouz; Pezeshki Rad, Masoud; Tavakoli, Maryam

    2015-03-01

     Alveolar hydatid disease is a highly malignant form of echinococcosis caused by the larvae of the cestode echinococcus multilocularis. Alveolar hydatid disease always affects the liver and can metastasise to the lung and brain. Early diagnosis and precise evaluation of the localization as well as the extent of lesions are essential for treatment. In this report, we present ultrasound and computed tomography findings in a patient with hepatic alveolar echinococcosis. The patient, who was presented with hepatomegaly, jaundice, and an infiltrative solid tumor, diagnosed by ultrasound and computed tomography. In contrast to hydatid cyst caused by echinococcus granulosus, this is a rare disease in Iran. PMID:25773697

  14. Immunopathogenesis of hepatitis C virus infection

    Microsoft Academic Search

    Anthony J Freeman; George Marinos; Rosemary A Ffrench; Andrew R Lloyd

    2001-01-01

    Hepatitis C virus, a recently identified member of the family Flaviviridae, is an important cause of chronic viral hepatitis and cirrhosis. There are similarities in the nature of the immune response to this pathogen with immunity in other flavivirus and hepatotropic virus infections, such as hepatitis B. However, the high rate of viral persistence after primary hepatitis C infection, and

  15. [Cholecystolithiasis as a cause of local hepatitis].

    PubMed

    Dolimov, K S; Il'khamov, F A; Abdumazhidov, A Sh; Tukhtamuradov, Z Z; Dolimov, T K; Pivnitski?, I O

    2014-08-01

    In an acute inflammation of gallbladder inflammatory process spreads on surrounding tissues, including hepatic tissue, what causes the regional hepatitis occurrence. In some patients, suffering calculous cholecystitis on background of transition of inflammatory process from gallbladder to hepatic tissue likewise a regional hepatitis, hyperbilirubinemia, the skin yellowness are revealed, what simulates choledocholithiasis and obturation jaundice. PMID:25417284

  16. Coinfection of Chronic Hepatitis B and Fasciolosis

    Microsoft Academic Search

    M. Demirci; M. Isler; B. Cicioglu Aridogan; A. Senol; M. Korkmaz

    2004-01-01

    Chronic hepatitis B and fasciolosis are associated with the induction of T-cell responses polarized to the Th2 subtype. Interferon-alpha enhances innate immunity as well as Th1 immune response. We present a male patient with chronic hepatitis B and fasciolosis who responded to chronic hepatitis treatment with hepatitis B virus (HBV) vaccine, interferon-alpha-2b and lamivudine.

  17. [Hepatitis E: an emerging disease].

    PubMed

    Bonnet, D; Kamar, N; Izopet, J; Alric, L

    2012-06-01

    The hepatitis E virus is endemic in countries with poor sanitation, where it has many similarities with the hepatitis A virus. It causes a strictly human, feco-oral transmitted, acute, self-limited hepatitis in young adults. The outcome is excellent, except in pregnant women and cirrhotic patients, who experience a high mortality rate. The first cases described in industrialized countries were travellers coming from endemic areas. However, there is now growing evidence that locally-acquired hepatitis E is common in these areas, where it is an emergent disease, despite it is still misdiagnosed. In industrialized countries, hepatitis E spreads sporadically and has a predilection for elderly men with comorbidity, particularly chronic liver diseases. The mortality seems to be higher in this population. In these areas, hepatitis E is due to the genotype 3 virus that is thought to be zoonotically transmitted by pigs and wild boar. Hepatitis E may evolve towards a chronic infection in immunocompromised subjects, particularly in solid organ-transplanted patients. In case of chronic infection, it may cause liver fibrosis and cirrhosis. The diagnosis of hepatitis E is based on serological tests (IgM and IgG) and detection of the viral genome by reverse transcription polymerase chain reaction (RT-PCR) on blood and stools. Acute hepatitis E does not require any treatment but in chronically infected patients, a sustained viral response and finally a definitive viral clearance has been observed after a three-month course of low-dose ribavirin (600 to 800 mg/day). Two vaccines underwent successful human trials but are not yet commercially available. PMID:22405325

  18. The hepatic-arterial/portal-venous scintiangiogram in alcoholic hepatitis

    SciTech Connect

    Stewart, C.; Sakimura, I.; Siegel, M.E.; Harley, H.; Lee, K.

    1984-01-01

    This study was designed to identify abnormalities in the hepatic-arterial/portal-venous scintiangiogram (SA) in alcoholic hepatitis (AH). SA's were performed in 35 patients with acute alcoholic hepatitis (AAH), 8; acute alcoholic hepatitis superimposed on cirrhosis (A/C), 14; and cirrhosis (C), 13. Posterior flows were done with a bolus of 10 mCi Tc-99m sulfur colloid with computer time-activity curves over the liver and left kidney. Curves were analyzed for per cent of hepatic arterial (HA) and portal venous contribution using the slope ratio method. Hepatic arterialization was estimated from the angle of the HA component of the curve. Reversal of the relative contribution of the hepatic and portal components of total flow were seen in all groups. Although quite severe in AH, the degree of reversal could not be used to differentiate among the groups. The average HA angle in AAH was 48.3 +- 8.1, in A/C 41.5 +- 10.6, and in C 30.4 +- 12.1. In reviewing the data of only those in the acute clinical phase of AH and not the recovery phase (1 AAH, 3 A/C) and those without other causes of alteration in hepatic arterialization (1 hepatoma, 1 portalcaval shunt, 6 renal failure), the average HA angle in AAH was 50.1 +- 6.6, 45.4 +- 8.2 in A/C, and 23.2 +- 4.2 in C. In 6 with renal failure (2 C, 2AAH, 2 A/C) the HA angle ws 52.7 +- 5.7. In all cases cirrhosis could be differentiated from both A/C (P=.05) and AAH (P<.01) using the HA angle. In absence of renal failure, portal shunt, or hepatoma, P was <.01 in both comparisons.

  19. Hepatitis G virus infection in fulminant hepatic failure

    PubMed Central

    Saiz, J; Sans, M; Mas, A; Olmedo, E; Forns, X; Lopez-Labrador, F; Restrepo, J; Costa, J; Salmeron, J; Guilera, M; Ampurdanes, S; Sanchez-Tapias, J; de Anta, M T J.; Rodes, J

    1997-01-01

    Background—RNA sequences of the recently identified hepatitis GB virus C (HGBV-C), also named hepatitis G virus (HGV), have been detected in patients with idiopathic fulminant hepatic failure (FHF) but the role of this agent in the disease remains controversial. ?Aims—To investigate the presence and implications of HGV infection in a large series of Spanish patients with FHF. ?Patients—Sixty eight patients with FHF, including 19 with idiopathic disease, were studied. In 28 cases, studies were performed before and after liver transplantation. For comparison 200 volunteer blood donors and 22 patients transplanted for chronic liver disease were also studied. ?Methods—HGV RNA was measured in serum by reverse transcriptase polymerase chain reaction of the 5' non-coding region. ?Results—Evidence of HGV infection was found in 3% (6/200) of blood donors and in 19% (13/68) of patients with FHF. HGV infection was more frequent in patients with hepatitis B (24%, 6/25) or hepatitis D (42%, 5/12), than in patients with idiopathic disease (11%, 2/19). Half of the patients with HGV infection used illicit intravenous drugs. Specific clinical features associated with HGV infection were not identified. A very high rate of infection with HGV was observed in patients who underwent liver transplantation, either for FHF (60%, 15/24) or chronic liver disease (45%, 9/20). ?Conclusions—In our geographical area, HGV infection is relatively frequent in FHF, but it does not seem to play a major role in idiopathic cases. ?? Keywords: viral hepatitis; hepatitis G virus; fulminant hepatic failure; liver transplantation PMID:9414981

  20. Hepatic progenitors for liver disease: current position

    PubMed Central

    Conigliaro, Alice; Brenner, David A; Kisseleva, Tatiana

    2010-01-01

    Liver regeneration restores the original functionality of hepatocytes and cholangiocytes in response to injury. It is regulated on several levels, with different cellular populations contributing to this process, eg, hepatocytes, liver precursor cells, intrahepatic stem cells. In response to injury, mature hepatocytes have the capability to proliferate and give rise to new hepatocytes and cholangiocytes. Meanwhile, liver precursor cells (oval cells) have become the most recognized bipotential precursor cells in the damaged liver. They rapidly proliferate, change their cellular composition, and differentiate into hepatocytes and cholangiocytes to compensate for the cellular loss and maintain liver homeostasis. There is a growing body of evidence that oval cells originate from the intrahepatic stem cell(s), which in turn give(s) rise to epithelial, including oval cells, and/or other hepatic cells of nonepithelial origin. Since there is a close relationship between the liver and hematopoiesis, bone marrow derived cells can also contribute to liver regeneration by the fusion of myeloid cells with damaged hepatocytes, or differentiation of mesenchymal stem cells into hepatocyte-like cells. The current review discusses the contribution of different cells to liver regeneration and their characteristics. PMID:24198509

  1. Comparison of imatinib, nilotinib and silymarin in the treatment of carbon tetrachloride-induced hepatic oxidative stress, injury and fibrosis

    PubMed Central

    Shaker, Mohamed E.; Zalata, Khaled R.; Mehal, Wajahat Z.; Shiha, Gamal E.; Ibrahim, Tarek M.

    2013-01-01

    Effective and well-tolerated anti-fibrotic drugs are currently lacking. Therefore, this study was carried out to investigate the potential anti-fibrotic effects of imatinib, nilotinib and silymarin on established hepatic fibrosis in the carbon tetrachloride (CCl4) rat model. Male Wistar rats received intraperitoneal injections of CCl4 twice weekly for 8 weeks, as well as daily intraperitoneal treatments of imatinib (10 and 20 mg/kg), nilotinib (10 and 20 mg/kg) and silymarin (100 mg/kg) during the last 4 weeks of CCl4-intoxication. At the end of the study, hepatic damage was evaluated by analysis of liver function tests and hepatic oxidative stress parameters. Hepatic fibrosis was evaluated by histopathology and morphometry, as well as collagen and 4-hydroxyproline contents. Nilotinib (20 mg/kg) was the most effective treatment to counteract CCl4-induced hepatic injury as indicated by liver function tests and histopathology. Nilotinib (10 mg/kg), nilotinib (20 mg/ kg) and silymarin (100 mg/kg) treatments reduced the mean score of hepatic fibrosis by 31%, 68% and 47%, respectively, and hepatic collagen content by 47%, 49% and 18%, respectively in CCl4-treated rats. Hepatic morphometric evaluation and 4-hydroxyproline content revealed that CCl4-induced fibrosis was ameliorated significantly by nilotinib (20 mg/kg) and imatinib (20 mg/kg). Unlike nilotinib, imatinib (20 mg/kg) showed some sort of hepatic injury evidenced by elevation of serum aminotransferases and total bilirubin levels, and hepatic total nitrate/nitrite content, as well as characteristic anisonucleosis visualized with the hematoxylineosin staining. In conclusion, this study provides the evidence that nilotinib exerts anti-fibrotic activity and suggests that it may be valuable in the treatment of hepatic fibrosis in humans. PMID:21316382

  2. Hepatitis B in pregnancy

    PubMed Central

    Borgia, Guglielmo; Carleo, Maria Aurora; Gaeta, Giovanni Battista; Gentile, Ivan

    2012-01-01

    Chronic hepatitis B virus (HBV) infection affects about 350 million individuals worldwide. Management of HBV infection in pregnancy is difficult because of several peculiar and somewhat controversial aspects. The aim of the present review is to provide a tool that may help physicians to correctly manage HBV infection in pregnancy. This review focuses on (1) the effect of pregnancy on HBV infection and of HBV infection on pregnancy; (2) the potential viral transmission from mother to newborn despite at-birth prophylaxis with immunoglobulin and vaccine; (3) possible prevention of mother-to-child transmission through antiviral drugs, the type of antiviral drug to use considering their efficacy and potential teratogenic effect, and the timing of their administration and discontinuation; and (4) the evidence for the use of elective caesarean section vs vaginal delivery and the possibility of breastfeeding. PMID:23002336

  3. Hepatic Encephalopathy: Historical Remarks

    PubMed Central

    Amodio, Piero

    2014-01-01

    The history of hepatic encephalopathy (HE) is briefly reviewed since the beginning of western medicine by Hippocrates. For about 2000 years the main evidence was the mere association between jaundice, fever and delirium. A clear link between delirium and cirrhosis was proven in the 17th century by Morgagni. In subsequent times the focus was manly the descriptions of symptoms and the only pathophysiological improvement was the evidence that jaundice, per se, does not alter brain function. Only at the end of the 19th century Hann et al proved the role of portal-systemic shunt and pf nitrogenous derivates in the pathophysiology of the syndrome. A terrific development of knowledge occurred in the last 60 years, after the works of Sherlock in London. Nowadays some consensus about HE was reached, so that new developments will likely occur. PMID:26041956

  4. Hepatic encephalopathy: historical remarks.

    PubMed

    Amodio, Piero

    2015-03-01

    The history of hepatic encephalopathy (HE) is briefly reviewed since the beginning of western medicine by Hippocrates. For about 2000 years the main evidence was the mere association between jaundice, fever and delirium. A clear link between delirium and cirrhosis was proven in the 17th century by Morgagni. In subsequent times the focus was manly the descriptions of symptoms and the only pathophysiological improvement was the evidence that jaundice, per se, does not alter brain function. Only at the end of the 19th century Hann et al proved the role of portal-systemic shunt and pf nitrogenous derivates in the pathophysiology of the syndrome. A terrific development of knowledge occurred in the last 60 years, after the works of Sherlock in London. Nowadays some consensus about HE was reached, so that new developments will likely occur. PMID:26041956

  5. FastStats: Viral Hepatitis

    MedlinePLUS

    ... States, 2014, table 37 [PDF - 9.8 MB] Mortality Number of deaths: 8,157 Deaths per 100, ... in Health Data Interactive Viral Hepatitis Related Links Mortality data Centers for Disease Control and Prevention: Viral ...

  6. Hepatic fat accumulation and regulation of FAT/CD36: an effect of hepatic irradiation.

    PubMed

    Martius, Gesa; Alwahsh, Salamah Mohammad; Rave-Fränk, Margret; Hess, Clemens Friedrich; Christiansen, Hans; Ramadori, Giuliano; Malik, Ihtzaz Ahmed

    2014-01-01

    Irradiation is known to induce inflammation and affect fat metabolic pathways. The current study investigates hepatic fat accumulation and fatty acid transportation in a rat model of single dose liver irradiation (25-Gy). Rat livers were selectively irradiated in-vivo (25-Gy), sham-irradiated rats served as controls. Hepatic lipids were studied by colorimetric assays in liver and serum. Intracellular lipids, protein and mRNA were studied by Nile red staining, immunohistology, Western Blot analysis and RT-PCR in liver, respectively. Changes in FAT/CD36 expression were studied in-vitro in a human monocyte cell line U937 after irradiation in presence or absence of infliximab (IFX). Nile Red staining of liver cryosections showed a quick (12-48 h) increase in fat droplets. Accordingly, hepatic triglycerides (TG) and free fatty acids (FFA) were elevated. An early increase (3-6 h) in the serum level of HDL-C, TG and cholesterol was measured after single dose irradiation followed by a decrease thereafter. Furthermore, expression of the fat transporter protein FAT/CD36 was increased, immunohistochemistry revealed basolateral and cytoplasmic expression in hepatocytes. Moreover, apolipoprotein-B100, -C3 and enzymes (acetyl-CoA carboxylase, lipoprotein-lipase, carnitine-palmitoyltransferase, malonyl-CoA-decarboxylase) involved in fat metabolism were induced at 12-24 h. Early activation of the NFk? pathway (I?B?) by TNF-? was seen, followed by a significant elevation of serum markers for liver damage (AST and GLDH). TNF-? blockage by anti-TNF-? in cell culture (U937) prevented the increase of FAT/CD36 caused by irradiation. Selective liver irradiation is a model for rapid induction of steatosis hepatis and fat accumulation could be triggered by irradiation-induced inflammatory mediators (e.g. TNF-?). PMID:25197426

  7. Hepatic fat accumulation and regulation of FAT/CD36: an effect of hepatic irradiation

    PubMed Central

    Martius, Gesa; Alwahsh, Salamah Mohammad; Rave-Fränk, Margret; Hess, Clemens Friedrich; Christiansen, Hans; Ramadori, Giuliano; Malik, Ihtzaz Ahmed

    2014-01-01

    Irradiation is known to induce inflammation and affect fat metabolic pathways. The current study investigates hepatic fat accumulation and fatty acid transportation in a rat model of single dose liver irradiation (25-Gy). Rat livers were selectively irradiated in-vivo (25-Gy), sham-irradiated rats served as controls. Hepatic lipids were studied by colorimetric assays in liver and serum. Intracellular lipids, protein and mRNA were studied by Nile red staining, immunohistology, Western Blot analysis and RT-PCR in liver, respectively. Changes in FAT/CD36 expression were studied in-vitro in a human monocyte cell line U937 after irradiation in presence or absence of infliximab (IFX). Nile Red staining of liver cryosections showed a quick (12-48 h) increase in fat droplets. Accordingly, hepatic triglycerides (TG) and free fatty acids (FFA) were elevated. An early increase (3-6 h) in the serum level of HDL-C, TG and cholesterol was measured after single dose irradiation followed by a decrease thereafter. Furthermore, expression of the fat transporter protein FAT/CD36 was increased, immunohistochemistry revealed basolateral and cytoplasmic expression in hepatocytes. Moreover, apolipoprotein-B100, -C3 and enzymes (acetyl-CoA carboxylase, lipoprotein-lipase, carnitine-palmitoyltransferase, malonyl-CoA-decarboxylase) involved in fat metabolism were induced at 12-24 h. Early activation of the NFk? pathway (I?B?) by TNF-? was seen, followed by a significant elevation of serum markers for liver damage (AST and GLDH). TNF-? blockage by anti-TNF-? in cell culture (U937) prevented the increase of FAT/CD36 caused by irradiation. Selective liver irradiation is a model for rapid induction of steatosis hepatis and fat accumulation could be triggered by irradiation-induced inflammatory mediators (e.g. TNF-?). PMID:25197426

  8. Hepatic haemangiomata: diagnosis and management.

    PubMed Central

    Larcher, V F; Howard, E R; Mowat, A P

    1981-01-01

    Five cases of hepatic haemangioma are described, and a sixth (previously reported) is reviewed. Clinical features, investigation, and management are described to show the great variability of the complications and prognosis. Five children presented in the first 10 weeks of life with hepatomegaly; 4 developed congestive cardiac failure; 3 had cutaneous haemangiomata. One child presented at age 4 years with hepatomegaly and anaemia, and on investigation had features of chronic disseminated intravascular coagulation. Focal decrease or patchiness in hepatic uptake of technetium-99m colloid, and abnormal intrahepatic circulation was shown in all cases. In 3 children liver biopsy was performed to exclude malignant disease. In one patient there was spontaneous regression of the tumour by age 3 years. In 3 cases hepatic artery ligation was necessary to control congestive cardiac failure which had persisted despite treatment with digoxin, diuretics, and oral corticosteroids, a procedure which was without complications after up to 8 years. One infant with intractable portal hypertension, hepatic vein obstruction, and severe cholestasis died with persisting alimentary haemorrhage and intra-abdominal sepsis. One child aged 4 years showed no immediate response to hepatic artery ligation but the size of her tumour got smaller and the clinical features diminished after irradiation. These tumours cause considerable morbidity and have a high reported mortality. If congestive cardiac failure is not rapidly controlled, hepatic artery ligation should be performed. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7469456

  9. Problems of protection against virus B hepatitis

    PubMed Central

    Polakoff, Sheila

    1976-01-01

    Various methods have been employed to reduce hepatitis B infections among patients and staff at high risk. Routine screening tests of all blood donors for hepatitis B surface antigen has reduced post-transfusion hepatitis B. After a control and prevention programme was instituted hepatitis B cross-infection was eliminated from haemodialysis units in Britain. Prophylaxis with specific immunoglobulin reduced attack rates of clinical hepatitis B, after accidental inoculation with infective material, to about 2%. Endemic hepatitis B in hospitals for the mentally subnormal remains a problem. PMID:981104

  10. Mitochondrial iron accumulation exacerbates hepatic toxicity caused by hepatitis C virus core protein.

    PubMed

    Sekine, Shuichi; Ito, Konomi; Watanabe, Haruna; Nakano, Takafumi; Moriya, Kyoji; Shintani, Yoshizumi; Fujie, Hajime; Tsutsumi, Takeya; Miyoshi, Hideyuki; Fujinaga, Hidetake; Shinzawa, Seiko; Koike, Kazuhiko; Horie, Toshiharu

    2015-02-01

    Patients with long-lasting hepatitis C virus (HCV) infection are at major risk of hepatocellular carcinoma (HCC). Iron accumulation in the livers of these patients is thought to exacerbate conditions of oxidative stress. Transgenic mice that express the HCV core protein develop HCC after the steatosis stage and produce an excess of hepatic reactive oxygen species (ROS). The overproduction of ROS in the liver is the net result of HCV core protein-induced dysfunction of the mitochondrial respiratory chain. This study examined the impact of ferric nitrilacetic acid (Fe-NTA)-mediated iron overload on mitochondrial damage and ROS production in HCV core protein-expressing HepG2 (human HCC) cells (Hep39b cells). A decrease in mitochondrial membrane potential and ROS production were observed following Fe-NTA treatment. After continuous exposure to Fe-NTA for six days, cell toxicity was observed in Hep39b cells, but not in mock (vector-transfected) HepG2 cells. Moreover, mitochondrial iron ((59)Fe) uptake was increased in the livers of HCV core protein-expressing transgenic mice. This increase in mitochondrial iron uptake was inhibited by Ru360, a mitochondrial Ca(2+) uniporter inhibitor. Furthermore, the Fe-NTA-induced augmentation of mitochondrial dysfunction, ROS production, and cell toxicity were also inhibited by Ru360 in Hep39b cells. Taken together, these results indicate that Ca(2+) uniporter-mediated mitochondrial accumulation of iron exacerbates hepatocyte toxicity caused by the HCV core protein. PMID:25545986

  11. Fenofibrate Does Not Affect Burn-Induced Hepatic Endoplasmic Reticulum Stress

    PubMed Central

    Hiyama, Yaeko; Marshall, Alexandra H.; Kraft, Robert; Arno, Anna; Jeschke, Marc G.

    2013-01-01

    Background Burn injury causes major metabolic derangements such as hypermetabolism, hyperlipidemia, and insulin resistance and is associated with liver damage, hepatomegaly, and hepatic endoplasmic reticulum (ER) stress. Although the physiological consequences of such derangements have been delineated, the underlying molecular mechanisms remain unknown. Previously, it was shown that fenofibrate improves patient outcome by attenuating post-burn stress responses. Methods Fenofibrate, a peroxisome proliferator-activated receptor (PPAR)-? agonist, regulates liver lipid metabolism and has been used to treat hypertriglyceridemia and hypercholesterolemia for many years. The aim of the present study is to determine the effects of fenofibrate on burn-induced hepatic morphologic and metabolic changes. We randomized rats to sham, burn injury, and burn injury plus fenofibrate. Animals were sacrificed and livers were assessed at 24 or 48 hours post-burn. Results Burn injury decreased albumin and increased alanine transaminase (p = 0.1 vs. sham), indicating liver injury. Fenofibrate administration did not restore albumin or decrease alanine transaminase. In addition, ER stress was significantly increased after burn injury both with and without fenofibrate (p < 0.05 vs. sham). Burn injury increased fatty acid metabolism gene expression (p < 0.05 vs. sham), downstream of PPAR?. Fenofibrate treatment increased fatty acid metabolism further, which reduced post-burn hepatic steatosis (burn vs. sham p < 0.05, burn+fenofibrate vs. sham not significant). Conclusions Fenofibrate did not alleviate thermal injury induced hepatic ER stress and dysfunction but reduced hepatic steatosis by modulating hepatic genes related to fat metabolism. PMID:23866789

  12. Dysregulation of hepatic iron with aging: implications for heat stress-induced oxidative liver injury.

    PubMed

    Bloomer, Steven A; Brown, Kyle E; Buettner, Garry R; Kregel, Kevin C

    2008-04-01

    Environmental heat stress is associated with an age-related increase in hepatic oxidative damage and an exaggerated state of oxidative stress. The purpose of this investigation was to evaluate the regulation of hepatic iron after heat stress. A secondary aim was to determine a potential role for iron in heat stress-induced liver injury. Hyperthermia-induced alterations in hepatic iron were evaluated in young (6 mo) and old (24 mo) Fischer 344 rats by exposing them to a two-heat stress protocol. Livers were harvested at several time points after the second heating and assayed for labile and nonheme iron. In the control condition, there was no difference in labile iron between age groups. Both labile iron and storage iron were not altered by hyperthermia in young rats, but both were increased immediately after heating in old rats. To evaluate a role for iron in liver injury, hepatic iron content was manipulated in young and old rats, and then both groups were exposed to heat stress. Iron administration to young rats significantly increased hepatic iron content and ferritin but did not affect markers of lipid peroxidation under control conditions or after heat stress. In old rats, iron chelation with deferoxamine prevented the increase in nonheme iron, labile iron, ferritin, and lipid peroxidation after heat stress. These results suggest that iron may play a role in hepatic injury after hyperthermia. Thus, dysregulation of iron may contribute to the gradual decline in cellular and physiological function that occurs with aging. PMID:18272664

  13. Protective effect of Rumex patientia (English Spinach) roots on ferric nitrilotriacetate (Fe-NTA) induced hepatic oxidative stress and tumor promotion response.

    PubMed

    Lone, Irshad A; Kaur, Gurpreet; Athar, Mohammad; Alam, M Sarwar

    2007-10-01

    In this communication, we document the antioxidant potential of ethanolic extract of Rumex patientia L. (Polygonaceae) roots and its chemopreventive effects against Fe-NTA mediated hepatic oxidative stress, hepatotoxicity and tumor promotion response. The extract exhibited high polyphenolic content, potent reducing power and significantly scavenged free radicals (including several reactive oxygen species (ROS) and reactive nitrogen species (RNS)). The extract also significantly and dose dependently protected against oxidative damage to lipids and DNA. These results indicated R. patientia root extract to exert a potent antioxidant activity in vitro. The efficacy of extract was also evaluated in vivo and it was found to exert a potent protective affect in acute oxidative tissue injury animal model: ferric nitrilotriacetate (Fe-NTA) induced hepatotoxicity in mice. Administration of Fe-NTA (9 mg/kg body weight, i.p.) to mice led to a significant oxidative stress and allied damage in liver tissues and induced hyperproliferation. A significant depletion was observed in GSH content and enzymes implicated in its metabolism. Attenuation also occurred in activities of other hepatic antioxidant enzymes including SOD, CAT, and GPX. Fe-NTA also incited hyperproliferation response elevating ornithine decarboxylase activity and [(3)H]-thymidine incorporation into DNA. Histopathological investigations and liver function tests (LFT) indicated Fe-NTA to cause extensive hepatic damage. However, prophylactic treatment with R. patientia root extract at a dose regimen of 100-200mg/kg body weight for a week not only restored hepatic antioxidant armory close to normal, but also significantly precluded oxidative damage restoring normal hepatic architecture and levels of hepatic damage markers. The data obtained in the present study illustrates R. patientia roots to possess potent antioxidant and free radical scavenging activities and thwart oxidative damage and hyperproliferation in hepatic tissues. PMID:17517459

  14. Testing for the Hepatitis C Virus

    MedlinePLUS

    ... C Virus" /> Consumer Summary – Sept. 13, 2013 Testing for the Hepatitis C Virus Formats View PDF ( ... longer for bleeding to stop Understanding Hepatitis C Testing How do I know if I have the ...

  15. Surveillance for Viral Hepatitis - United States, 2012

    MedlinePLUS

    ... Home Page Share Compartir Surveillance for Viral Hepatitis – United States, 2012 Entire report in a printable format [PDF - ... Reported cases of acute hepatitis A, by state ? United States, 2008–2012 Table 2.2 Clinical characteristics of ...

  16. All Kids Need Hepatitis B Shots

    MedlinePLUS

    ... Newborn babies should receive their first shot of hepatitis B vaccine at birth before leaving the hospital. If your ... be done at the same visit as vaccinations. Hepatitis B vaccine is one of the safest vaccines available. It ...

  17. Hepatic tumor angiography: a subject review

    SciTech Connect

    Chuang, V.P.

    1983-09-01

    The dual blood supply of the normal hepatic parenchyma and the single arterial supply of hepatic neoplasms are important factors in the interpretation of celiac and hepatic arteriograms. Depending on whether the hepatic artery, portal vein, or both are opacified, three types of hepatogram can occur: arterial, portal, or mixed. On the celiac arteriogram, the densely opacified hepatic parenchyma makes the less well opacified tumor appear relatively hypovascular; and conversely, on the hepatic arteriogram the nonopacified portal flow has a ''wash-out'' effect on the normal parenchyma so that the neoplasm remains hypervascular. Thus most hepatic neoplasms are hypervascular on the hepatic arteriogram, and conversion of a hypervascular tumor to a hypovascular one is indicative of its response to treatment.

  18. [Treatment of hepatitis C].

    PubMed

    Schneider, M D; Kronenberger, B; Zeuzem, S; Sarrazin, C

    2015-04-01

    Chronic hepatitis C virus (HCV) infection is the major cause of liver cirrhosis, hepatocellular carcinoma and liver transplantation in the western world. The development and approval of nine directly acting antiviral drugs in recent years has led to a dramatic improvement in therapeutic efficacy accompanied by fewer side effects. With current treatment options sustained virologic response in more than 90?% of patients can be achieved depending on HCV genotype, liver cirrhosis and prior therapies. Modern HCV treatment regimens are interferon-free and should be administered for 12-24 weeks. Shorter courses are possible in selected patients. For the treatment of HCV genotype 1 infection combinations of either the nucleotide polymerase inhibitor sofosbuvir with the protease inhibitor simeprevir or with one of the two NS5A inhibitors daclatasvir or ledipasvir on the one hand or triple DAA therapy of paritaprevir, ombitasvir and dasabuvir on the other hand are applicable. Ribavirin has still a role as an add-on in difficult to treat patients. PMID:25762008

  19. Genetics Home Reference: Congenital hepatic fibrosis

    MedlinePLUS

    ... gastrointestinal ; gene ; hepatic ; hepatosplenomegaly ; hypertension ; infection ; inheritance ; inheritance pattern ; inherited ; intestine ; kidney ; lymph ; malformation ; polycystic kidney ; prevalence ; recessive ; renal ; ...

  20. Parvovirus B19 Associated Hepatitis

    PubMed Central

    Bihari, Chhagan; Rastogi, Archana; Saxena, Priyanka; Rangegowda, Devraj; Chowdhury, Ashok; Gupta, Nalini; Sarin, Shiv Kumar

    2013-01-01

    Parvovirus B19 infection can present with myriads of clinical diseases and syndromes; liver manifestations and hepatitis are examples of them. Parvovirus B19 hepatitis associated aplastic anemia and its coinfection with other hepatotropic viruses are relatively underrecognized, and there is sufficient evidence in the literature suggesting that B19 infections can cause a spectrum of liver diseases from elevation of transaminases to acute hepatitis to fulminant liver failure and even chronic hepatitis. It can also cause fatal macrophage activation syndrome and fibrosing cholestatic hepatitis. Parvovirus B19 is an erythrovirus that can only be replicate in pronormoblasts and hepatocytes, and other cells which have globosides and glycosphingolipids in their membrane can also be affected by direct virus injury due to nonstructural protein 1 persistence and indirectly by immune mediated injury. The virus infection is suspected in bone marrow aspiration in cases with sudden drop of hemoglobin and onset of transient aplastic anemia in immunosuppressed or immunocompetent patients and is confirmed either by IgM and IgG positive serology, PCR analysis, and in situ hybridization in biopsy specimens or by application of both. There is no specific treatment for parvovirus B19 related liver diseases, but triple therapy regimen may be effective consisting of immunoglobulin, dehydrohydrocortisone, and cyclosporine. PMID:24232179

  1. Generation of functional hepatic cells from pluripotent stem cells

    PubMed Central

    Han, Songyan; Bourdon, Alice; Hamou, Wissam; Dziedzic, Noelle; Goldman, Orit; Gouon-Evans, Valerie

    2014-01-01

    Liver diseases affect millions of people worldwide, especially in developing country. According to the American Liver Foundation, nearly 1 in every 10 Americans suffers from some form of liver disease. Even though, the liver has great ability to self-repair, in end-stage liver diseases including fibrosis, cirrhosis, and liver cancer induced by viral hepatitis and drugs, the liver regenerative capacity is exhausted. The only successful treatment for chronic liver failure is the whole liver transplantation. More recently, some clinical trials using hepatocyte transplantation have shown some clinical improvement for metabolic liver diseases and acute liver failure. However, the shortage of donor livers remains a life-threatening challenge in liver disease patients. To overcome the scarcity of donor livers, hepatocytes generated from embryonic stem cell or induced pluripotent stem cell differentiation cultures could provide an unlimited supply of such cells for transplantation. This review provides an updated summary of hepatic differentiation protocols published so far, with a characterization of the hepatic cells generated in vitro and their ability to regenerate damaged livers in vivo following transplantation in pre-clinical liver deficient mouse models. PMID:25364624

  2. RELATED ARTICLES Pricey Hepatitis C Drug Draws

    E-print Network

    Bogyo, Matthew

    as this dangerous alphabet of infectious diseases Hepatitis A,B,C,D, and E kills nearly as many people as does HIV/AIDS. Hepatitis B and C are most well known and justifiably feared because they cause chronic liver cirrhosis and liver cancer, very often leading to death. Hepatitis B is transmitted from an infected mother to her

  3. 78 FR 46247 - World Hepatitis Day, 2013

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-31

    ...threats, and both hepatitis B and C can become chronic...disease. Vaccines for hepatitis A and B are crucial to preventing...is no vaccine against hepatitis C, but through early...and in many cases even cure the infection....

  4. Hepatic toxicity resulting from cancer treatment

    Microsoft Academic Search

    Theodore S. Lawrence; John M. Robertson; Mitchell S. Anscher; Randy L. Jirtle; William D. Ensminger; Luis F. Fajardo

    1995-01-01

    Radiation-induced liver disease (RILD), often called radiation hepatitis, is a syndrome characterized by the development of anicteric ascites approximately 2 weeks to 4 months after hepatic irradiation. There has been a renewed interest in hepatic irradiation because of two significant advances in cancer treatment: three dimensional radiation therapy treatment planning and bone marrow transplantation using total body irradiation. RILD resulting

  5. 79 FR 44257 - World Hepatitis Day, 2014

    Federal Register 2010, 2011, 2012, 2013, 2014

    2014-07-31

    ...Proclamation 9151 of July 25, 2014 World Hepatitis Day, 2014 By the President of the United...in twelve people are living with viral hepatitis. In the United States, millions of...unaware of their infection status. Viral hepatitis can persist undetected for many...

  6. Taxonomic Classification of Hepatitis A Virus

    Microsoft Academic Search

    Ian D. Gust; Anthony G. Coulepis; Stephen M. Feinstone; Stephen A. Locarnini; Yasuo Moritsugu; Raphael Najera; Gunter Siegl

    1983-01-01

    Summary Sufficient data have accumulated to permit the ICTV Ad Hoc Study Group on the Taxonomy of Hepatitis Viruses to recognize hepatitis A virus as a picornavirus. Within the family Picornaviridae, hepatitis A virus closely resembles members of the genus Enterovirus.Copyright © 1983 S. Karger AG, Basel

  7. Drug-induced chronic hepatic disease.

    PubMed

    Zimmerman, H J

    1979-05-01

    A number of chronic hepatic lesions can result from adverse reactions to medicinal agents. Such lesions include a form of chronic active hepatitis; hepatic steatosis, phoepholipidosis and granulomatosis; several vascular lesions; two types of noncirrhotic portal hypertension; several types of cirrhosis and several neoplasms. PMID:221760

  8. Hepatitis B vaccine nonresponse and celiac disease

    Microsoft Academic Search

    Kyung W. Noh; Gregory A. Poland; Joseph A. Murray

    2003-01-01

    OBJECTIVES:There is a genetic predisposition to hepatitis B vaccine nonresponse. The link between human leukocyte antigen (HLA) genotype and ineffective development of immunity to the hepatitis B vaccine has been characterized in multiple studies. Celiac disease has a strong association with a particular HLA genotype of DQ2; interestingly, this HLA genotype is seen in association with nonresponders to the hepatitis

  9. Development of a Spontaneous Liver Disease Resembling Autoimmune Hepatitis in Mice Lacking Tyro3, Axl and Mer Receptor Tyrosine Kinases

    PubMed Central

    Qi, Nan; Liu, Peipei; Zhang, Yue; Wu, Hui; Chen, Yongmei; Han, Daishu

    2013-01-01

    Autoimmune hepatitis (AIH) is a severe type of chronic liver disease. The lack of appropriate animal models has resulted in a limited understanding regarding the etiology of AIH. Here, we demonstrated that mice deficient in Tyro3, Axl and Mer (TAM) receptor tyrosine kinases (RTKs) developed persistent inflammatory liver damage resembling AIH. Tyro3?/?Axl?/?Mer?/? triple mutant (TAM?/?) mice exhibited chronic hepatitis, manifested by progressive appearance of interface hepatitis, immune cell infiltrations and elevated inflammatory cytokine levels in the liver. Accordingly, increased levels of transaminases were observed. Moreover, characteristic autoantibodies and high levels of plasma immunoglobulin G for AIH were detected as TAM?/? mice aged. Finally, we provided evidence that the liver damage in TAM?/? mice mainly result from bone marrow-derived cells and could be rescued by transplantation of WT bone marrow cells. Results suggest that TAM RTKs play an important role in maintaining immune tolerance of the liver. PMID:23799121

  10. Dental infection with hepatitis B.

    PubMed

    Williams, S V; Pattison, C P; Berquist, K R

    1975-06-23

    We performed a prospective study to assess the risk of patients acquiring infection following routine professional contact with two dentists incubating type B viral hepatitis. Serum samples from patients exposed during the six weeks before onset of hepatitis in the dentists were tested for hepatitis B surface antigen and for antibody to the antigen shortly after illness developed and again six months later. Household members of exposed patients served as a control group. None of the exposed patients or controls became ill with hepititis, and none developed antigen. Three of the 237 exposed patients developed antibody, as did four of the 245 controls. The difference between exposed patients and controls was not significant. These results do not support the hypothesis that these two dentists transmitted infection to their patients. PMID:805849

  11. Drug-induced hepatic steatosis.

    PubMed

    Amacher, David E; Chalasani, Naga

    2014-05-01

    Several drugs have been associated with the potential for drug-induced hepatic steatosis (DIHS) and/or phospholipidosis (DIPL), a lysosomal storage disorder. Drug-induced hepatic steatosis is generally a chronic but reversible affliction and may involve drug accumulation in the liver. Fat accumulation may be either macrovesicular or microvesicular in nature. Commonly used medications associated with DIHS include amiodarone, valproate, tamoxifen, methotrexate, and some chemotherapeutic and antiretroviral agents. Two recently approved medications for the treatment of hereditary homozygous hypercholesterolemia have also been noted to cause hepatic steatosis. For some compounds such as methotrexate and tamoxifen, the underlying metabolic risk factors such as obesity and metabolic syndrome may exacerbate their potential to cause DIHS and its progression. In this article, the authors discuss the preclinical screening and mechanisms of DIHS and DIPL, and review specific examples of drugs commonly used in clinical practice that are known to cause DIHS. PMID:24879984

  12. [Hepatitis C and insulin resistance].

    PubMed

    Seirafi, Mariam; Negro, Francesco

    2008-09-01

    In the course of a chronic infection with the hepatitis C virus, the fibrosis progression rate varies among individuals, and depends on the existence of certain co-factors. In this context, a growing interest has emerged and has focused on insulin resistance. In fact, the hepatitis C virus is now recognized as being responsible for a direct interference with the insulin signalling pathway. This insulin resistance of viral origin, in combination with an eventual insulin resistance associated with an existing metabolic syndrome, can therefore accelerate its evolution to a type II diabetes. Independently of its pathogenesis, insulin resistance occurring in chronic hepatitis C causes a fatty liver, contributes to the progression towards cirrhosis, and narrows the chances of a successful antiviral therapy. It is therefore crucial to recognize it in order to correct it. PMID:18831405

  13. Aloe-induced Toxic Hepatitis

    PubMed Central

    Yang, Ha Na; Kim, Young Mook; Kim, Byoung Ho; Sohn, Kyoung Min; Choi, Myung Jin; Choi, Young Hee

    2010-01-01

    Aloe has been widely used in phytomedicine. Phytomedicine describes aloe as a herb which has anti-inflammatory, anti-proliferative, anti-aging effects. In recent years several cases of aloe-induced hepatotoxicity were reported. But its pharmacokinetics and toxicity are poorly described in the literature. Here we report three cases with aloe-induced toxic hepatitis. A 57-yr-old woman, a 62-yr-old woman and a 55-yr-old woman were admitted to the hospital for acute hepatitis. They had taken aloe preparation for months. Their clinical manifestation, laboratory findings and histologic findings met diagnostic criteria (RUCAM scale) of toxic hepatitis. Upon discontinuation of the oral aloe preparations, liver enzymes returned to normal level. Aloe should be considered as a causative agent in hepatotoxicity. PMID:20191055

  14. [Prevention of viral hepatitis B and C infections--jurisdiction and certification difficulties].

    PubMed

    Olesiak-Andryszczak, Ma?gorzata; Cnota, Wojciech; Sodowski, Krzysztof

    2004-01-01

    The number of the cases for payment because of viral hepatitis B and C inflammation is significant. Because of the greater patients' notice of the disease and portal of infection, lawyer's opinion accessibility and poor economical situation of society the claims for damages seems to be more popular. The lawyers specialize in medical law. This is the reason to pay more attention to prevention of infections. Besides the hospital infections there is problem of viral hepatitis B and C infection as the occupational disease with all health and juridical consequences. These problems concern specially operative specialties therefore gynecology and obstetrics among the others. The aim of our study was to analyze jurisdiction and certification difficulties in context of occupational disease and cases for payment because of viral hepatitis B and C infections. We also try to answer the question what are possibilities to prevent infections and to defence in law suits. PMID:15884247

  15. Hepatitis C, stigma and cure

    PubMed Central

    Marinho, Rui Tato; Barreira, David Pires

    2013-01-01

    The infection with hepatitis C virus (HCV) is one of the most important global chronic viral infections worldwide. It is estimated to affect around 3% of the world population, about 170-200 million people. Great part of the infections are asymptomatic, the patient can be a chronic carrier for decades without knowing it. The most severe consequences of the chronic infection are liver cirrhosis and hepatocellular carcinoma, which appears in 20%-40% of the patients, leading to hepatic failure and death. The HCV was discovered 25 years ago in 1989, is a RNA virus and classified by the World Health Organization as an oncogenic one. Hepatocellular carcinoma is one of the most important cancers, the fifth worldwide in terms of mortality. It has been increasing in the Ocidental world, mainly due to chronic hepatitis C. Hepatitis C is not only a liver disease and a cause of cirrhosis, but also a mental, psychological, familiar, and social disease. The stigma that the infected person sometimes carries is tremendous having multiple consequences. The main cause is lack of adequate information, even in the health professionals setting. But, besides the “drama” of being infected, health professionals, family, society and the infected patients, must be aware of the chance of real cure and total and definitive elimination of the virus. The treatment for hepatitis C has begun in the last 80´s with a percentage of cure of 6%. Step by step the efficacy of the therapy for hepatitis C is rapidly increasing and nowadays with the very new medications, the so called Direct Antiviral Agents-DAAs of new generation, is around 80%-90%. PMID:24187444

  16. Hepatic lipase deficiency.

    PubMed

    Connelly, P W; Hegele, R A

    1998-12-01

    Hepatic lipase (HL) is an enzyme that is made primarily by hepatocytes (and also found in adrenal gland and ovary) and hydrolyzes phospholipids and triglycerides of plasma lipoproteins. It is secreted and bound to the hepatocyte surface and readily released by heparin. It is a member of the lipase superfamily and is homologous to lipoprotein lipase and pancreatic lipase. The enzyme can be divided into an NH2-terminal domain containing the catalytic site joined by a short spanning region to a smaller COOH-terminal domain. The NH2-terminal portion contains an active site serine in a pentapeptide consensus sequence, Gly-Xaa-Ser-Xaa-Gly, as part of a classic Ser-Asp-His catalytic triad, and a putative hinged loop structure covering the active site. The COOH-terminal domain contains a putative lipoprotein-binding site. The heparin-binding sites may be distributed throughout the molecule, with the characteristic elution pattern from heparin-sepharose determined by the COOH-terminal domain. Of the three N-linked glycosylation sites, Asn-56 is required for efficient secretion and enzymatic activity. HL is hypothesized to directly couple HDL lipid metabolism to tissue/cellular lipid metabolism. The potential significance of the HL pathway is that it provides the hepatocyte with a mechanism for the uptake of a subset of phospholipids enriched in unsaturated fatty acids and may allow the uptake of cholesteryl ester, free cholesterol, and phospholipid without catabolism of HDL apolipoproteins. HL can hydrolyze triglyceride and phospholipid in all lipoproteins, but is predominant in the conversion of intermediate density lipoproteins to LDL and the conversion of post-prandial triglyceride-rich HDL into the postabsorptive triglyceride-poor HDL. HL plays a secondary role in the clearance of chylomicron remnants by the liver. Human post-heparin HL activity is inversely correlated with intermediate density lipoprotein cholesterol concentration only in subjects with a hyperlipidemia involving VLDL. This is consistent with intermediate-density lipoproteins being a substrate for HL. HDL cholesterol has been reported to be inversely correlated to HL activity, and on this basis it has been suggested that lowering HL would increase HDL cholesterol. However, the correlation could also be due to a common hormonal factor such as estrogen, which has been shown to up-regulate apoAI and HDL cholesterol and lower HL. A striking feature of severe deficiency of HL is the increase in HDL cholesterol and apolipoprotein AI and an approximately 10-fold increase in HDL triglyceride. Hyper-alpha-triglyceridemia is not a feature of antiatherogenic HDL. HL binds not only to heparan, but also to the LDL receptor-related protein. It has been suggested that enzymatically inactive HL can play a role in hepatic lipoprotein uptake, forming a "bridge" by binding to the lipoprotein and to the cell surface. This raises the interesting possibility that production and secretion of mutant inactive HL could promote clearance of VLDL remnants. We have described a rare family with HL deficiency. Affected patients are compound heterozygotes for a mutation of Ser267 to Phe that results in an inactive enzyme and a mutation of Thr383 to Met that results in impaired secretion and reduced specific activity. Human HL deficiency in the context of a second factor causing hyperlipidemia is strongly associated with premature coronary artery disease. Recently, it has been reported that mutations affecting the structure of HL (e.g., T383M) are relatively frequent in the Finnish population. A C-to-T polymorphism in the promotor region of the HL gene is associated with lowered HL activity and less strongly with increased HDL cholesterol. In summary, there is a good understanding of what HL does in lipoprotein metabolism; however, there is little understanding of its physiological importance, that is, why HL does what it does. (ABSTRACT TRUNCATED) PMID:9885775

  17. Lactobacillus fermentum ZYL0401 Attenuates Lipopolysaccharide-Induced Hepatic TNF-? Expression and Liver Injury via an IL-10- and PGE2-EP4-Dependent Mechanism

    PubMed Central

    Lv, Longxian; Yang, Jianzhuan; Lu, Haifeng; Li, Lanjuan

    2015-01-01

    Lipopolysaccharide (LPS) has essential role in the pathogenesis of D-galactosamine-sensitized animal models and alcoholic liver diseases of humans, by stimulating release of pro-inflammatory mediators that cause hepatic damage and intestinal barrier impairment. Oral pretreatment of probiotics has been shown to attenuate LPS-induced hepatic injury, but it is unclear whether the effect is direct or due to improvement in the intestinal barrier. The present study tested the hypothesis that pretreatment with probiotics enables the liver to withstand directly LPS-induced hepatic injury and inflammation. In a mouse model of LPS-induced hepatic injury, the levels of hepatic tumor necrosis factor-alpha (TNF-?) and serum alanine aminotransferase (ALT) of mice with depleted intestinal commensal bacteria were not significantly different from that of the control models. Pre-feeding mice for 10 days with Lactobacillus fermentum ZYL0401 (LF41), significantly alleviated LPS-induced hepatic TNF-? expression and liver damage. After LF41 pretreatment, mice had dramatically more L.fermentum-specific DNA in the ileum, significantly higher levels of ileal cyclooxygenase (COX)-2 and interleukin 10 (IL-10) and hepatic prostaglandin E2 (PGE2). However, hepatic COX-1, COX-2, and IL-10 protein levels were not changed after the pretreatment. There were also higher hepatic IL-10 protein levels after LPS challenge in LF41-pretreaed mice than in the control mice. Attenuation of hepatic TNF-? was mediated via the PGE2/E prostanoid 4 (EP4) pathway, and serum ALT levels were attenuated in an IL-10-dependent manner. A COX-2 blockade abolished the increase in hepatic PGE2 and IL-10 associated with LF41. In LF41-pretreated mice, a blockade of IL-10 caused COX-2-dependent promotion of hepatic PGE2, without affecting hepatic COX-2levels. In LF41-pretreated mice, COX2 prevented enhancing TNF-? expression in both hepatic mononuclear cells and the ileum, and averted TNF-?-mediated increase in intestinal permeability. Together, we demonstrated that LF41 pre-feeding enabled the liver to alleviate LPS-induced hepatic TNF-? expression and injury via a PGE2-EP4- and IL-10-dependent mechanism. PMID:25978374

  18. Diagnosis of Minimal Hepatic Encephalopathy

    PubMed Central

    Weissenborn, Karin

    2014-01-01

    Minimal hepatic encephalopathy (mHE) has significant impact upon a liver patient's daily living and health related quality of life. Therefore a majority of clinicians agree that mHE should be diagnosed and treated. The optimal means for diagnosing mHE, however, is controversial. This paper describes the currently most frequently used methods—EEG, critical flicker frequency, Continuous Reaction time Test, Inhibitory Control Test, computerized test batteries such as the Cognitive Drug Research test battery, the psychometric hepatic encephalopathy score (PHES) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)—and their pros and cons.

  19. Diagnosis of minimal hepatic encephalopathy.

    PubMed

    Weissenborn, Karin

    2015-03-01

    Minimal hepatic encephalopathy (mHE) has significant impact upon a liver patient's daily living and health related quality of life. Therefore a majority of clinicians agree that mHE should be diagnosed and treated. The optimal means for diagnosing mHE, however, is controversial. This paper describes the currently most frequently used methods-EEG, critical flicker frequency, Continuous Reaction time Test, Inhibitory Control Test, computerized test batteries such as the Cognitive Drug Research test battery, the psychometric hepatic encephalopathy score (PHES) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)-and their pros and cons. PMID:26041959

  20. Replication of hepatitis C virus.

    PubMed

    Moradpour, Darius; Penin, François; Rice, Charles M

    2007-06-01

    Exciting progress has recently been made in understanding the replication of hepatitis C virus, a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. The development of complete cell-culture systems should now enable the systematic dissection of the entire viral lifecycle, providing insights into the hitherto difficult-to-study early and late steps. These efforts have already translated into the identification of novel antiviral targets and the development of new therapeutic strategies, some of which are currently undergoing clinical evaluation. PMID:17487147

  1. Damage Tolerance of Composites

    NASA Technical Reports Server (NTRS)

    Hodge, Andy

    2007-01-01

    Fracture control requirements have been developed to address damage tolerance of composites for manned space flight hardware. The requirements provide the framework for critical and noncritical hardware assessment and testing. The need for damage threat assessments, impact damage protection plans, and nondestructive evaluation are also addressed. Hardware intended to be damage tolerant have extensive coupon, sub-element, and full-scale testing requirements in-line with the Building Block Approach concept from the MIL-HDBK-17, Department of Defense Composite Materials Handbook.

  2. Hepatic encephalopathy: An approach to its multiple pathophysiological features

    PubMed Central

    Perazzo, Juan Carlos; Tallis, Silvina; Delfante, Amalia; Souto, Pablo Andrés; Lemberg, Abraham; Eizayaga, Francisco Xavier; Romay, Salvador

    2012-01-01

    Hepatic encephalopathy (HE) is a neuropsychiatric complex syndrome, ranging from subtle behavioral abnormalities to deep coma and death. Hepatic encephalopathy emerges as the major complication of acute or chronic liver failure. Multiplicity of factors are involved in its pathophysiology, such as central and neuromuscular neurotransmission disorder, alterations in sleep patterns and cognition, changes in energy metabolism leading to cell injury, an oxidative/nitrosative state and a neuroinflammatory condition. Moreover, in acute HE, a condition of imminent threat of death is present due to a deleterious astrocyte swelling. In chronic HE, changes in calcium signaling, mitochondrial membrane potential and long term potential expression, N-methyl-D-aspartate-cGMP and peripheral benzodiazepine receptors alterations, and changes in the mRNA and protein expression and redistribution in the cerebral blood flow can be observed. The main molecule indicated as responsible for all these changes in HE is ammonia. There is no doubt that ammonia, a neurotoxic molecule, triggers or at least facilitates most of these changes. Ammonia plasma levels are increased two- to three-fold in patients with mild to moderate cirrhotic HE and up to ten-fold in patients with acute liver failure. Hepatic and inter-organ trafficking of ammonia and its metabolite, glutamine (GLN), lead to hyperammonemic conditions. Removal of hepatic ammonia is a differentiated work that includes the hepatocyte, through the urea cycle, converting ammonia into GLN via glutamine synthetase. Under pathological conditions, such as liver damage or liver blood by-pass, the ammonia plasma level starts to rise and the risk of HE developing is high. Knowledge of the pathophysiology of HE is rapidly expanding and identification of focally localized triggers has led the development of new possibilities for HE to be considered. This editorial will focus on issues where, to the best of our knowledge, more research is needed in order to clarify, at least partially, controversial topics. PMID:22489256

  3. Monoacylglycerol Lipase Controls Endocannabinoid and Eicosanoid Signaling and Hepatic Injury in Mice

    PubMed Central

    Cao, Zongxian; Mulvihill, Melinda M.; Mukhopadhyay, Partha; Xu, Huan; Erdélyi, Katalin; Hao, Enkui; Holovac, Eileen; Haskó, György; Cravatt, Benjamin F.; Nomura, Daniel K.; Pacher, Pál

    2013-01-01

    Background & Aims The endocannabinoid and eicosanoid lipid signaling pathways have important roles in inflammatory syndromes. Monoacylglycerol lipase (MAGL) links these pathways, hydrolyzing the endocannabinoid 2-arachidonoylglycerol to generate the arachidonic acid precursor pool for prostaglandin production. We investigated whether blocking MAGL protects against inflammation and damage from hepatic ischemia/reperfusion (I/R) and other insults. Methods We analyzed the effects of hepatic I/R in mice given the selective MAGL inhibitor JZL184, in Mgll?/? mice, FAAH?/? mice, and in Cnr1?/? and Cnr2?/? mice, which have disruptions in the cannabinoid receptors 1 and 2 (CB1/2). Liver tissues were collected and analyzed, along with cultured hepatocytes and Kupffer cells. We measured endocannabinoids, eicosanoids, and markers of inflammation, oxidative stress, and cell death using molecular biology, biochemistry, and mass spectrometry analyses. Results Wild-type mice given JZL184 and Mgll?/? mice were protected from hepatic I/R injury by a mechanism that involved increased endocannabinoid signaling via CB2 and reduced production of eicosanoids in the liver. JZL184 suppressed the inflammation and oxidative stress that mediate hepatic I/R injury. Hepatocytes were the major source of hepatic MAGL activity and endocannabinoid and eicosanoid production. JZL184 also protected from induction of liver injury by D-(+)-galactosamine and lipopolysaccharides or CCl4. Conclusions MAGL promotes hepatic injury via endocannabinoid and eicosanoid signaling; blockade of this pathway protects mice from liver injury. MAGL inhibitors might be developed to treat for conditions that expose the liver to oxidative stress and inflammatory damage. PMID:23295443

  4. Hepatic cytomembranous inclusions in patients with type C chronic hepatitis

    Microsoft Academic Search

    Seishiro Watanabe; Mutsunori Shirai; Keiji Arima; Mikio Nishioka; Miyuki Ohbayashi; Eugene R. Schiff

    1995-01-01

    Electron microscopic studies of the liver biopsy specimens from two patients with chronic type C hepatitis revealed cytomembranous structures. Cylindrical confronting cisternae were identified for the first time in the cytoplasm of macrophages in the specimen which was taken during ?-interferon therapy. Tubuloreticular inclusions were observed in both patients with and without therapy. Although the cytomembranous inclusions are not specific

  5. Oxidative stress and hepatitis C virus

    PubMed Central

    2013-01-01

    The disproportionate imbalance between the systemic manifestation of reactive oxygen species and body’s ability to detoxify the reactive intermediates is referred to as oxidative stress. Several biological processes as well as infectious agents, physiological or environmental stress, and perturbed antioxidant response can promote oxidative stress. Oxidative stress usually happens when cells are exposed to more electrically charged reactive oxygen species (ROS) such as H2O2 or O2-. The cells’ ability to handle such pro-oxidant species is impeded by viral infections particularly within liver that plays an important role in metabolism and detoxification of harmful substances. During liver diseases (such as hepatocellular or cholestatic problems), the produced ROS are involved in transcriptional activation of a large number of cytokines and growth factors, and continued production of ROS and Reactive Nitrogen Species (RNS) feed into the vicious cycle. Many human viruses like HCV are evolved to manipulate this delicate pro- and antioxidant balance; thus generating the sustainable oxidative stress that not only causes hepatic damage but also stimulates the processes to reduce treatment of damage. In this review article, the oxidant and antioxidant pathways that are perturbed by HCV genes are discussed. In the first line of risk, the pathways of lipid metabolism present a clear danger in accumulation of viral induced ROS. Viral infection leads to decrease in cellular concentrations of glutathione (GSH) resulting in oxidation of important components of cells such as proteins, DNA and lipids as well as double strand breakage of DNA. These disorders have the tendency to lead the cells toward cirrhosis and hepatocellular carcinoma in adults due to constant insult. We have highlighted the importance of such pathways and revealed differences in the extent of oxidative stress caused by HCV infection. PMID:23923986

  6. Pediatric knowledge about acute viral hepatitis.

    PubMed

    Franca, Rita; Silva, Luciana; Melo, Maria Clotildes; Cavalcante, Suzy; Lima, Bruno; Rocha, Anita; Gomes, Cristiana; Franca, Mônica

    2004-06-01

    Knowledge about hepatotropic viruses is crucial for pediatricians because of the high prevalence of viral hepatitis during childhood. The multiplicity of hepatotropic viruses, the spectrum of acute and chronic infections, and the sequels of viral hepatitis result in a need for physicians to better understand the clinical and epidemiological context of patients with viral hepatitis, as well as the importance of prevention measures for hepatitis. A descriptive cross-sectional study was made of pediatrician's knowledge about viral hepatitis, through questionnaires to 574 pediatricians, with no obligation of identification. The pediatricians were recruited among those who attended a national Congress of Pediatrics in Brasília, Brazil. Among these pediatricians, 50.1% frequently treated cases of hepatitis, and 74.7% indicated that they had knowledge of the existence of five hepatotropic viruses; 14.5% knew about at least four types of hepatitis complications, while only 7.7% and 4.3% were able to correctly diagnose viral hepatitis A and B, respectively. Many (28.4%) did not know how to treat the patients adequately. Only 37.5% had already recommended vaccination against hepatitis B. Only 50.2% of the pediatricians had been vaccinated against hepatitis B. We concluded that it is crucial to make pediatricians more knowledgeable about viral hepatitis, through continued education programs, especially emphasizing prevention procedures. PMID:15476061

  7. [Epidemiology of viral hepatitis in Mexico].

    PubMed

    Panduro, Arturo; Escobedo Meléndez, Griselda; Fierro, Nora A; Ruiz Madrigal, Bertha; Zepeda-Carrillo, Eloy Alfonso; Román, Sonia

    2011-01-01

    The main etiology of liver disease in Mexico is alcohol and viral hepatitis. The aim of the present study was to analyze the current epidemiology of viral hepatitis in Mexico. From 2000 to 2007 the Ministry of Health reported 192 588 cases of hepatitis, 79% HAV, 3.3% HBV, 6% HCV, and 12% without a specific etiologic factor. Due to high endemic areas for HBV infection in native Mexican population, limitations in the diagnostic sensitivity and specificity of the serological immunoassays used to date and presence of occult hepatitis B in the country, the real prevalence of HBV infection could be even higher than HCV in Mexico. Hepatitis E virus in cirrhotic patients and in porcine farms could at least partially explain the cases of hepatitis that are diagnosed without a specific etiologic agent. Specific strategies to establish control regulations against viral hepatitis infections in Mexico are proposed. PMID:21877071

  8. Physiological control of NKT cell-dependent hepatitis induction by extracellular adenosine

    PubMed Central

    Subramanian, Meenakshi; Kini, Radhika; Madasu, Manasa; Ohta, Akiko; Nowak, Michael; Exley, Mark; Sitkovsky, Michail; Ohta, Akio

    2015-01-01

    Summary Extracellular adenosine regulates inflammatory responses via A2A adenosine receptor (A2AR). A2AR-deficiency results in much exaggerated acute hepatitis, indicating non-redundancy of adenosine-A2AR pathway in inhibitory mechanisms of immune activation. To identify a critical target of immunoregulatory effect of extracellular adenosine, we focused on NKT cells, which play an indispensable role in hepatitis. A2AR agonist abolished NKT cell-dependent induction of acute hepatitis by Con A or ?-galactosylceramide (?-GalCer), corresponding to down-regulation of activation markers and cytokines in NKT cells and of NK cell co-activation. These results show that A2AR signaling can down-regulate NKT cell activation and suppress NKT cell-triggered inflammatory responses. Next, we hypothesized that NKT cells might be under physiological control of the adenosine-A2AR pathway. Indeed, both Con A and ?-GalCer induced more severe hepatitis in A2AR?/? mice than in wild-type controls. Transfer of A2AR?/? NKT cells into A2AR-expressing recipients resulted in exaggeration of Con A-induced liver damage, suggesting that NKT cell activation is controlled by endogenous adenosine via A2AR, and this physiological regulatory mechanism of NKT cells is critical in the control of tissue-damaging inflammation. The current study suggests the possibility to manipulate NKT cell activity in inflammatory disorders through intervention to the adenosine-A2AR pathway. PMID:24448964

  9. Hepatitis C virus infection and glomerular disease.

    PubMed

    Fabrizi, F; Donato, F; Messa, P

    2014-06-01

    The association between hepatitis C virus (HCV) infection and chronic kidney disease (CKD) is well established and remains an area of intense research. HCV infection is associated with a large spectrum of histo-pathological lesions in both native and transplanted kidneys. The frequency of kidney damage in HCV-infected patients appears low even if is not fully detailed. The most frequent HCV-associated renal lesion is type I membrano-proliferative glomerulonephritis, usually in the context of type II mixed cryoglobulinemia. Various approaches have been tried for the treatment of HCV-related glomerulonephritis, including immunosuppressive therapy (corticosteroids and cytotoxic agents), plasma exchange and antiviral agents. Antiviral treatment of HCV-associated glomerulonephritis has shown encouraging results. Immunosuppressive therapy is particularly recommended for cryoglobulinemic kidney disease. Two distinct approaches should be considered for the treatment of HCV-associated cryoglobulinemic glomerulonephritis according to the level of proteinuria and kidney failure. Some evidence on rituximab therapy for HCV-related cryoglobulinemic glomerulonephritis exists but several questions related to its use need to be addressed. PMID:24988205

  10. 8 Immunopathogenesis of hepatitis C

    Microsoft Academic Search

    Barbara Rehermann; Gabriele MISSALE; Carolina BONI; Simona URBANI

    2000-01-01

    Print this page SUMMARY The type of cell-mediated responses expressed at the early stages of HBV infection can influence the subsequent outcome of hepatitis B. Indeed, recovery is associated with efficient activation of mechanisms of the innate immunity, which seem to be responsible for the early inhibition of viral replication. A subsequent activation of HBV-specific T cells is probably crucial

  11. Treatment of chronic hepatitis B

    Microsoft Academic Search

    P. Marcellin; T. Asselah; N. Boyer

    2005-01-01

    SUMMARY. In the last years, marked progress has been made in the treatment of chronic hepatitis B. The efficacy of lami- vudine, the first nucleoside analogue available, is limited by the high incidence of resistance. Adefovir, which was recently approved has a comparable efficacy with a very low frequency of resistance. However, adefovir needs to be indefinitely administered as withdrawal

  12. HEPATIC SINUSOIDAL ENDOTHELIUM IN GOATS

    Microsoft Academic Search

    PL Wright; JA Clemett; KF Smith; WA Day; R Fraser

    1983-01-01

    The ultrastructure of the hepatic sinusoids of the goat was examined. Contrary to current belief concerning this and other ruminant species, we found the sinusoids to be lined by a smooth, continuous layer of endothelium, broken only by the presence of numerous, unoccluded fenestrae which provide a direct path of communication between the sinusoidal lumen and the space of Disse.

  13. Astroglial Dysfunction in Hepatic Encephalopathy

    Microsoft Academic Search

    Michael D. Norenberg

    1998-01-01

    While the pathogenesis of hepatic encephalopathy (HE) remains elusive, there is considerable evidence pointing to a key role of ammonia-induced dysfunction of astrocytes in this condition. Deficits in the ability of astrocytes to take up glutamate from the extracellular space may lead to abnormal glutamatergic neurotransmission. Furthermore, excessive stimulation of neuronal and glial glutamate receptors by elevated extracellular levels of

  14. Hepatitis C virus-mediated angiogenesis: Molecular mechanisms and therapeutic strategies

    PubMed Central

    Hassan, Mohamed; Selimovic, Denis; El-Khattouti, Abdelouahid; Soell, Martine; Ghozlan, Hanan; Haikel, Youssef; Abdelkader, Ola; Megahed, Mosaad

    2014-01-01

    Angiogenesis is an essential process for organ growth and repair. Thus, an imbalance in this process can lead to several diseases including malignancy. Angiogenesis is a critical step in vascular remodeling, tissue damage and wound healing besides being required for invasive tumor growth and metastasis. Because angiogenesis sets an important point in the control of tumor progression, its inhibition is considered a valuable therapeutic approach for tumor treatment. Chronic liver disease including hepatitis C virus (HCV) infection is one of the main cause for the development of hepatic angiogenesis and thereby plays a critical role in the modulation of hepatic angiogenesis that finally leads to hepatocellular carcinoma progression and invasion. Thus, understanding of the molecular mechanisms of HCV-mediated hepatic angiogenesis will help design a therapeutic protocol for the intervention of HCV-mediated angiogenesis and subsequently its outcome. In this review, we will focus on the molecular mechanisms of HCV-mediated hepatic angiogenesis and the related signaling pathways that can be target for current and under development therapeutic approaches. PMID:25400432

  15. Complications of radiofrequency ablation of hepatic tumors: Frequency and risk factors

    PubMed Central

    Fonseca, Alexandre Zanchenko; Santin, Stephanie; Gomes, Luiz Guilherme Lisboa; Waisberg, Jaques; Ribeiro Jr., Marcelo Augusto Fontenelle

    2014-01-01

    Radiofrequency ablation (RFA) has become an important option in the therapy of primary and secondary hepatic tumors. Surgical resection is still the best treatment option, but only a few of these patients are candidates for surgery: multilobar disease, insufficient liver reserve that will lead to liver failure after resection, extra-hepatic disease, proximity to major bile ducts and vessels, and co-morbidities. RFA has a low mortality and morbidity rate and is considered to be safe. Thus, complications occur and vary widely in the literature. Complications are caused by thermal damage, direct needle injury, infection and the patient’s co-morbidities. Tumor type, type of approach, number of lesions, tumor localization, underlying hepatic disease, the physician’s experience, associated hepatic resection and lesion size have been described as factors significantly associated with complications. The physician in charge should promptly recognize high-risk patients more susceptible to complications, perform a close post procedure follow-up and manage them early and adequately if they occur. We aim to describe complications from RFA of hepatic tumors and their risk factors, as well as a few techniques to avoid them. This way, others can decrease their morbidity rates with better outcomes. PMID:24672640

  16. Hepatic lipid profiling of deer mice fed ethanol using {sup 1}H and {sup 31}P NMR spectroscopy: A dose-dependent subchronic study

    SciTech Connect

    Fernando, Harshica; Bhopale, Kamlesh K.; Boor, Paul J.; Ansari, G.A. Shakeel; Kaphalia, Bhupendra S., E-mail: bkaphali@utmb.edu

    2012-11-01

    Chronic alcohol abuse is a 2nd major cause of liver disease resulting in significant morbidity and mortality. Alcoholic liver disease (ALD) is characterized by a wide spectrum of pathologies starting from fat accumulation (steatosis) in early reversible stage to inflammation with or without fibrosis and cirrhosis in later irreversible stages. Previously, we reported significant steatosis in the livers of hepatic alcohol dehydrogenase (ADH)-deficient (ADH{sup ?}) vs. hepatic ADH-normal (ADH{sup +}) deer mice fed 4% ethanol daily for 2 months [Bhopale et al., 2006, Alcohol 39, 179–188]. However, ADH{sup ?} deer mice fed 4% ethanol also showed a significant mortality. Therefore, a dose-dependent study was conducted to understand the mechanism and identify lipid(s) involved in the development of ethanol-induced fatty liver. ADH{sup ?} and ADH{sup +} deer mice fed 1, 2 or 3.5% ethanol daily for 2 months and fatty infiltration in the livers were evaluated by histology and by measuring dry weights of extracted lipids. Lipid metabolomic changes in extracted lipids were determined by proton ({sup 1}H) and {sup 31}phosphorus ({sup 31}P) nuclear magnetic resonance (NMR) spectroscopy. The NMR data was analyzed by hierarchical clustering (HC) and principle component analysis (PCA) for pattern recognition. Extensive vacuolization by histology and significantly increased dry weights of total lipids found only in the livers of ADH{sup ?} deer mice fed 3.5% ethanol vs. pair-fed controls suggest a dose-dependent formation of fatty liver in ADH{sup ?} deer mouse model. Analysis of NMR data of ADH{sup ?} deer mice fed 3.5% ethanol vs. pair-fed controls shows increases for total cholesterol, esterified cholesterol, fatty acid methyl esters (FAMEs), triacylglycerides and unsaturation, and decreases for free cholesterol, phospholipids and allylic and diallylic protons. Certain classes of neutral lipids (cholesterol esters, fatty acyl chain (-COCH{sub 2}-) and FAMEs) were also mildly increased in ADH{sup ?} deer mice fed 1 or 2% ethanol. Only small increases were observed for allylic and diallylic protons, FAMEs and unsaturations in ADH{sup +} deer mice fed 3.5% ethanol vs. pair-fed controls. PCA of NMR data showed increased clustering by gradual separation of ethanol-fed ADH{sup ?} deer mice groups from their respective pair-fed control groups and corresponding ethanol-fed ADH{sup +} deer mice groups. Our data indicate that dose of ethanol and hepatic ADH deficiency are two key factors involved in initiation and progression of alcoholic fatty liver disease. Further studies on characterization of individual lipid entities and associated metabolic pathways altered in our deer mouse model after different durations of ethanol feeding could be important to delineate mechanism(s) and identify potential biomarker candidate(s) of early stage ALD. -- Highlights: ? Dose-dependent ethanol-induced fatty liver was studied in deer mouse model. ? A NMR-based lipidomic approach with histology and dry lipid weights was used. ? We used principal component analysis (PCA) to analyze the NMR lipidomic data. ? Dose-dependent clustering patterns by PCA were compared among the groups.

  17. Pioglitazone retrieves hepatic antioxidant DNA repair in a mice model of high fat diet

    Microsoft Academic Search

    Pi-Jung Hsiao; Tusty-Jiuan Hsieh; Kung-Kai Kuo; Wei-Wen Hung; Kun-Bow Tsai; Ching-Hsiu Yang; Ming-Lung Yu; Shyi-Jang Shin

    2008-01-01

    BACKGROUND: Pioglitazone was reported to improve hepatic steatosis and necroinflammation in human studies. To investigate whether the hepato-protective effect of pioglitazone was associated with an improvement of antioxidant defense mechanism, oxidative DNA damage and repair activity were determined in a high fat diet model. Male C57BL\\/6 mice were respectively fed with a 30% fat diet, the same diet with pioglitazone

  18. CALL TO ACTION TO SCALE UP GLOBAL HEPATITIS RESPONSE

    E-print Network

    Straight, Aaron

    hepatitis and some 2 billion have been infected with hepatitis B virus. Most people with chronic hepatitis B. Such treatments must be made accessible to people who need them at affordable prices. Hepatitis B is preventable with a safe and effective vaccine, however, there are 240 million people living with chronic hepatitis B

  19. Occult HBV Infection among Chronic Hepatitis C Patients

    Microsoft Academic Search

    Aghazadeh R; Honarkar Z; Alavian SM; Samiee Sh; Saeedfar K; Ehsani MJ; Nori Nayer B

    Transmission routs of both hepatitis B and hepatitis C viruses are similar and infection with both viruses is common. Occult hepatitis B is a new entity in which serum HBsAg is negative but HBVDNA is detectable in serum or liver tissues. In this study the frequency of occult hepatitis B among patients with chronic hepatitis C and also their biochemical

  20. Hepatitis A: Old and New

    PubMed Central

    Cuthbert, Jennifer A.

    2001-01-01

    The hepatitis A virus (HAV), a picornavirus, is a common cause of hepatitis worldwide. Spread of infection is generally person to person or by oral intake after fecal contamination of skin or mucous membranes; less commonly, there is fecal contamination of food or water. Hepatitis A is endemic in developing countries, and most residents are exposed in childhood. In contrast, the adult population in developed countries demonstrates falling rates of exposure with improvements in hygiene and sanitation. The export of food that cannot be sterilized, from countries of high endemicity to areas with low rates of infection, is a potentially important source of infection. After ingestion and uptake from the gastrointestinal tract, the virus replicates in the liver and is excreted into the bile. Cellular immune responses to the virus lead to destruction of infected hepatocytes with consequent development of symptoms and signs of disease. Humoral immune responses are the basis for diagnostic serologic assays. Acute HAV infection is clinically indistinguishable from other causes of acute viral hepatitis. In young children the disease is often asymptomatic, whereas in older children and adults there may be a range of clinical manifestations from mild, anicteric infection to fulminant hepatic failure. Clinical variants include prolonged, relapsing, and cholestatic forms. Management of the acute illness is supportive, and complete recovery without sequelae is the usual outcome. Research efforts during World War II led to the development of passive immunoprophylaxis. Pooled immune serum globulin is efficacious in the prevention and attenuation of disease in exposed individuals. More recently, active immunoprophylaxis by vaccination has been accomplished. Future eradication of this disease can now be contemplated. PMID:11148002

  1. Eltrombopag in chronic hepatitis C

    PubMed Central

    Mih?il?, Romeo-Gabriel; Cip?ian, Remus-C?lin

    2014-01-01

    Chronic hepatitis C is a public health problem worldwide. Unfortunately, not all patients may benefit from antiviral therapy due to thrombocytopenia. Its causes are represented by portal hypertension and platelet sequestration in the spleen, decreased serum levels or activity of thrombopoietin, the bone marrow suppression induced by hepatitis C virus and a possible adverse effect of interferon. Thrombopoietin receptor analogs may contribute to increase platelet counts in these patients. Eltrombopag binds to another region of the thrombopoietin receptor compared to endogenous thrombopoietin and stimulates the proliferation and maturation of megakaryocytes and the platelet production in a dose-dependent manner. Eltrombopag has proven its effectiveness for the treatment of patients with primary immune thrombocytopenia. Its indication for other hemopathies or situations (like thrombocytopenia secondary to chemo- or radiotherapy, acute leukemia, myelodysplastic syndroms, acquired and hereditary bone marrow failure, and platelet donors) is under study. Eltrombopag may be particularly useful in patients with advanced chronic hepatitis or liver cirrhosis who require antiviral treatment. We present a minireview on the results of treatment with eltrombopag in patients chronically infected with hepatitis C virus, highlighting the benefits and mentioning possible adverse effects. In some studies eltrombopag increased the number of virological responses after clasical antiviral treatment of patients with chronic hepatitis C and reduced the transfusional requirements of those who had to be subjected to invasive surgery. Eltrombopag is a solution for many of these patients, which allows them receiving antiviral therapy and sometimes getting a sustained virological response, but they must be well monitored to prevent possible thromboembolic or bone marrow complications or liver failure occurrence. PMID:25253952

  2. Oxymatrine liposome attenuates hepatic fibrosis via targeting hepatic stellate cells

    PubMed Central

    Chai, Ning-Li; Fu, Qiang; Shi, Hui; Cai, Chang-Hao; Wan, Jun; Xu, Shi-Ping; Wu, Ben-Yan

    2012-01-01

    AIM: To investigate the potential mechanism of Arg-Gly-Asp (RGD) peptide-labeled liposome loading oxymatrine (OM) therapy in CCl4-induced hepatic fibrosis in rats. METHODS: We constructed a rat model of CCl4-induced hepatic fibrosis and treated the rats with different formulations of OM. To evaluate the antifibrotic effect of OM, we detected levels of alkaline phosphatase, hepatic histopathology (hematoxylin and eosin stain and Masson staining) and fibrosis-related gene expression of matrix metallopeptidase (MMP)-2, tissue inhibitor of metalloproteinase (TIMP)-1 as well as type?I?procollagen via quantitative real-time polymerase chain reaction. To detect cell viability and apoptosis of hepatic stellate cells (HSCs), we performed 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide assay and flow cytometry. To reinforce the combination of oxymatrine with HSCs, we constructed fluorescein-isothiocyanate-conjugated Arg-Gly-Asp peptide-labeled liposomes loading OM, and its targeting of HSCs was examined by fluorescent microscopy. RESULTS: OM attenuated CCl4-induced hepatic fibrosis, as defined by reducing serum alkaline phosphatase (344.47 ± 27.52 U/L vs 550.69 ± 43.78 U/L, P < 0.05), attenuating liver injury and improving collagen deposits (2.36% ± 0.09% vs 7.70% ± 0.60%, P < 0.05) and downregulating fibrosis-related gene expression, that is, MMP-2, TIMP-1 and type?I?procollagen (P < 0.05). OM inhibited cell viability and induced apoptosis of HSCs in vitro. RGD promoted OM targeting of HSCs and enhanced the therapeutic effect of OM in terms of serum alkaline phosphatase (272.51 ± 19.55 U/L vs 344.47 ± 27.52 U/L, P < 0.05), liver injury, collagen deposits (0.26% ± 0.09% vs 2.36% ± 0.09%, P < 0.05) and downregulating fibrosis-related gene expression, that is, MMP-2, TIMP-1 and type?I?procollagen (P < 0.05). Moreover, in vitro assay demonstrated that RGD enhanced the effect of OM on HSC viability and apoptosis. CONCLUSION: OM attenuated hepatic fibrosis by inhibiting viability and inducing apoptosis of HSCs. The RGD-labeled formulation enhanced the targeting efficiency for HSCs and the therapeutic effect. PMID:22919254

  3. Epidemiology of Hepatitis B, C, E, and G Virus Infections and Molecular Analysis of Hepatitis G Virus Isolates in Bolivia

    Microsoft Academic Search

    NAMI KONOMI; CHIAKI MIYOSHI; CARLOS LA FUENTE ZERAIN; TIAN-CHENG LI; YASUYUKI ARAKAWA; KENJI ABE

    1999-01-01

    Prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis G virus (HGV), and hepatitis E virus (HEV) was investigated among 574 healthy blood donors in Bolivia. HCV RNA and HGV RNA in the serum were identified by a nested reverse transcription-PCR using primers derived from the 5* untranslated region (5* UTR). We also tested for hepatitis B surface

  4. Laser Damage Lab

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Optical Damage Threshold Testing Instrumentation at NASA Langley Research Center. This work was sanctioned and funded by Code Q, R, & AE to develop a new standard for damage testing various types of optical materials and coatings. Laser Induced Damage Threshold (LIDT) testing is a destructive test procedure to determine the minimum applied laser energy level that will result in damage and is referred to as the damage threshold. The damage threshold is often the critical limitation in the section of optical materials for use in high-energy laser systems.The test station consists of diagnostic equipment, beam conditioning optical elements, an inspection microscope and three lasers: a high energy pulsed ND: Yag, which develops 650mJ at 10 hz and outputs three wavelengths which include 1.06m, 532nm and 355 nm; a Ti:sapphire laser which produces a continuum of laser output from 790nm to 900nm; and a alignment HeNe, which looks yellow when mixed with the 2nd harmonic ND:Yag laser. Laser sources are used to perform damage threshold testing at the specific wavelength of interest.

  5. [Effect of liver damage in females on reactive changes in the livers of the progeny].

    PubMed

    Tsirel'nikov, N I

    1976-09-01

    The liver of 30-day ratlings was studied spectrocytophotometrically (glycogen, amino acid, RNA, and DNA content) and morphometrically (the size of the nuclei, nucleoli, mitotic index) 48 hours after the intragastric administration of CCI4; the mothers of these ratlings had sustained toxic hepatitis before pregnancy. The results obtained indicated that hepatitis sustained by the female animals not only influenced the morphological peculiarities and the histochemical properties of the liver of the progeny, but also largely conditioned the changes in the response of hepatocytes to the poison -- enhanced the damaging effect of the hepatotoxin. PMID:990471

  6. Hepatitis B antigen, hepatitis B antibody, and subtypes in leprosy.

    PubMed Central

    Sher, R; Mackay, M E; Macnab, G M; Kok, S H; Koornhof, H J

    1977-01-01

    The prevalence of hepatitis B antigen (HBsAg), hepatitis B antibody (HBsAb), and subtypes in 242 cases of leprosy is reported. Patients were divided into three subgroups, lepromatous (174), tuberculoid (55), and borderline (13). A total of 131 patients were tested on admission; the remaining 111 had been institutionalized for a period of 3 months or more when tested. Of the 131 cases tested on admission, 88 were retested 6 to 12 months after admission. There was no statistical difference in the incidence of HBsAg and HBsAb among the three groups or between normal controls and the leprosy patients. The predominant subtype was ADW (84.1%). After institutionalization, one lepromatous case converted to HBsAg positive and four converted to HBsAb positive. PMID:885608

  7. DNA Damage Response

    PubMed Central

    Giglia-Mari, Giuseppina; Zotter, Angelika; Vermeulen, Wim

    2011-01-01

    Structural changes to DNA severely affect its functions, such as replication and transcription, and play a major role in age-related diseases and cancer. A complicated and entangled network of DNA damage response (DDR) mechanisms, including multiple DNA repair pathways, damage tolerance processes, and cell-cycle checkpoints safeguard genomic integrity. Like transcription and replication, DDR is a chromatin-associated process that is generally tightly controlled in time and space. As DNA damage can occur at any time on any genomic location, a specialized spatio-temporal orchestration of this defense apparatus is required. PMID:20980439

  8. Hepatitis B Shots Are Recommended for All New Babies

    MedlinePLUS

    ... can be prevented by vaccination. Who recommends that all babies get hepatitis B vaccination at birth? Medical ... B virus. Hepatitis B Shots Are Recommended for All New Babies. Hepatitis B Vaccine Helps Protect Your ...

  9. 21 CFR 660.40 - Hepatitis B Surface Antigen.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...2013-04-01 2013-04-01 false Hepatitis B Surface Antigen. 660.40 Section...DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.40 Hepatitis B Surface Antigen. (a) Proper name...

  10. 65 FR 53316 - Interim Hepatitis B Vaccine Information Materials

    Federal Register 2010, 2011, 2012, 2013, 2014

    2000-09-01

    ...Disease Control and Prevention Interim Hepatitis B Vaccine Information Materials AGENCY...SUMMARY: A hepatitis B vaccine has recently been approved...information statement entitled, ``Hepatitis B Vaccine: What You Need to...

  11. Hepatitis B vaccine - what you need to know

    MedlinePLUS

    ... is taken in its entirety from the CDC Hepatitis B Vaccine Information Statement (VIS): http://www.cdc.gov/vaccines/ ... injecting drugs Being stuck with a used needle Hepatitis B vaccine: Why get vaccinated? Hepatitis B vaccine can prevent ...

  12. 21 CFR 660.40 - Hepatitis B Surface Antigen.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...2010-04-01 2010-04-01 false Hepatitis B Surface Antigen. 660.40 Section...DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.40 Hepatitis B Surface Antigen. (a) Proper name...

  13. 21 CFR 660.40 - Hepatitis B Surface Antigen.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 2011-04-01 2010-04-01 true Hepatitis B Surface Antigen. 660.40 Section...DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.40 Hepatitis B Surface Antigen. (a) Proper name...

  14. 21 CFR 660.40 - Hepatitis B Surface Antigen.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...2012-04-01 2012-04-01 false Hepatitis B Surface Antigen. 660.40 Section...DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.40 Hepatitis B Surface Antigen. (a) Proper name...

  15. 21 CFR 660.40 - Hepatitis B Surface Antigen.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...2014-04-01 2014-04-01 false Hepatitis B Surface Antigen. 660.40 Section...DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.40 Hepatitis B Surface Antigen. (a) Proper name...

  16. Occult hepatitis B virus infection in Lebanese patients with chronic hepatitis C liver disease

    Microsoft Academic Search

    S. Ramia; A. I. Sharara; M. El-Zaatari; F. Ramlawi; Z. Mahfoud

    2008-01-01

    Occult hepatitis B virus (HBV) infection, characterised by the presence of HBV infection with undetectable hepatitis B surface\\u000a antigen (HBsAg), was investigated in 98 Lebanese patients with chronic hepatitis C liver disease and 85 control subjects recruited\\u000a from eight institutions in different parts of the country. The prevalence of occult HBV infection ranged from 11.9% to 44.4%\\u000a in hepatitis C

  17. [Acute herpesviridae hepatitis during pregnancy: A review].

    PubMed

    Dochez, Vincent; Ducarme, Guillaume

    2015-06-01

    Viral hepatitis are well defined during pregnancy, including hepatitis A, B, C, D or E. In contrast, viral hepatitis called non-alphabetic, like viruses Herpesviridae family hepatitis [cytomegalovirus (CMV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV) or herpes simplex virus (HSV)] are rarely described. The aim of this article is to make a focus on the care of these viral herpesviridae hepatitis during pregnancy. Herpes hepatitis is more common during pregnancy, with a neonatal risk at peripartum period. VZV infection can cause disease to the fetus, with possible vertical transmission, and induce congenital or neonatal varicella. While EBV infection during pregnancy seems benign, the CMV is a high risk of birth defects. The management of these patients therefore depends on the gestational age, but especially the type of virus involved. The diagnosis is therefore essential to adapt treatment and obstetrical care. PMID:26033557

  18. In situ detection of lipid peroxidation and oxidative DNA damage in non-alcoholic fatty liver diseases

    Microsoft Academic Search

    Shuichi Seki; Takuya Kitada; Takao Yamada; Hiroki Sakaguchi; Kazuki Nakatani; Kenichi Wakasa

    2002-01-01

    Background\\/Aims: Although oxidative stress is an important candidate in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), the localization and pathological significance of oxidative stress-induced cellular damage in NAFLD remains unclear.Methods: Hepatic expression of 4-hydroxy-2?-nonenal (HNE) and 8-hydroxydeoxyguanosine (8-OHdG), as reliable markers of lipid peroxidation and oxidative DNA damage, respectively, was immunohistochemically investigated in NAFLD and the results were compared

  19. Controlling Opossum Damage 

    E-print Network

    Texas Wildlife Services

    2007-05-23

    damage; however, their pelts can be sold only during the furbearer season and with the proper licenses. Other furbearers include beaver, otter, mink, nutria, ringtailed cat, badger, skunk, weasel, raccoon, muskrat, fox and civet cat. Homeowners...

  20. LSD and Genetic Damage

    ERIC Educational Resources Information Center

    Dishotsky, Norman I.; And Others

    1971-01-01

    Reviews studies of the effects of lysergic acid diethylamide (LSD) on man and other organisms. Concludes that pure LSD injected in moderate doses does not cause chromosome or detectable genetic damage and is not a teratogen or carcinogen. (JM)

  1. Controlling Beaver Damage

    E-print Network

    Texas Wildlife Services

    2007-03-13

    Damage Controlling BEAVER B eavers (Castor canadensis) are the largest rodents in North America. Their range includes most of North America, from the northern parts of Canada and Alaska to northern Mexico. Beavers are aquatic rodents which live...

  2. Court Disallows Damage Claims

    ERIC Educational Resources Information Center

    Tomson, Bernard; Coplan, Norman

    1976-01-01

    In rejecting claims for damages, the Court finds that contract's "increase or decrease of cost" language is not applicable to added overhead costs and loss of labor efficiency resulting from delays over which the contractor has no control. (Author)

  3. DAMAGING AGENTS AND PROTECTION

    E-print Network

    Standiford, Richard B.

    limit the longevity of individual oaks. People who manage oak trees or woodlands are concerned of the ecological relationships between oaks and damaging agents. Oaks evolved under the challenge of various

  4. Controlling Woodpecker Damage 

    E-print Network

    Texas Wildlife Damage Management Service

    2008-04-15

    Several species of woodpeckers, flickers and sapsuckers live in Texas. They can be destructive when they drill holes in wooden structures. This publication discusses various controls and alternative methods for eliminating noise and damage....

  5. Controlling Armadillo Damage 

    E-print Network

    Texas Wildlife Services

    2007-03-13

    Armadillos are beneficial because they eat insects and other invertebrates, but they can damage lawns, gardens and structural foundations. They also are believed to transmit leprosy to humans. This leaflet focuses on control methods such as trapping...

  6. Northridge, CA Earthquake Damage

    USGS Multimedia Gallery

    The person in this image was a USGS employee at the time this was taken. Collection of USGS still images taken after the January 17, 1994 Northridge earthquake highlighting the damage to buildings and infrastructure....

  7. Composites Damage Tolerance Workshop

    NASA Technical Reports Server (NTRS)

    Gregg, Wayne

    2006-01-01

    The Composite Damage Tolerance Workshop included participants from NASA, academia, and private industry. The objectives of the workshop were to begin dialogue in order to establish a working group within the Agency, create awareness of damage tolerance requirements for Constellation, and discuss potential composite hardware for the Crew Launch Vehicle (CLV) Upper Stage (US) and Crew Module. It was proposed that a composites damage tolerance working group be created that acts within the framework of the existing NASA Fracture Control Methodology Panel. The working group charter would be to identify damage tolerance gaps and obstacles for implementation of composite structures into manned space flight systems and to develop strategies and recommendations to overcome these obstacles.

  8. Controlling Feral Hog Damage 

    E-print Network

    Texas Wildlife Services

    2008-04-15

    This publication discusses the distribution of feral hogs as well as their habitats, food habits and reproduction. Feral hogs can damage crops and kill lambs and kid goats. Methods of control are also explained....

  9. exploring drug users' illness representations of hiv, hepatitis b and hepatitis c using repertory grids

    Microsoft Academic Search

    Andrea Jennifer Walton; Frank Eves

    2001-01-01

    Hepatitis B and C viruses are more prevalent among injecting drug users than HIV. This study explored drug users' illness representations of hepatitis B and C using repertory grid methodology. Initially, nine drug users were presented with six elements including hepatitis B and C, and HIV. Constructs were elicited via the sequential form variation of the method of triads. Elements

  10. A prospective study of acute viral hepatitis with particular reference to hepatitis A*

    PubMed Central

    Locarnini, S. A.; Gust, I. D.; Ferris, A. A.; Stott, A. C.; Wong, M. L.

    1976-01-01

    In order to investigate the relationship of hepatitis A antigen to viral hepatitis, a prospective study was carried out on 97 patients admitted to Fairfield Hospital, Melbourne, with suspected viral hepatitis, and 3 of their family contacts. Evidence of infection with hepatitis A virus was obtained by detecting hepatitis A antigen in stools, and/or antibody to it in sera, by immune electron microscopy. Infection with hepatitis B virus was determined by testing for hepatitis B surface antigen and antibody in serum, by solid phase radioimmunoassay. Sixteen patients were found to have diseases other than viral hepatitis and 2 patients (child contacts) suffered no illness. There was clinical and/or biochemical evidence compatible with viral hepatitis in 82 patients, of whom 35 were confirmed as having hepatitis A and 31 as having hepatitis B infections. In the remaining 16 patients there was no evidence of infection with either hepatitis A or B virus. It is possible that some of these patients may have been infected with viral agents as yet unidentified. ImagesFig. 1 PMID:191207

  11. Hepatic histopathologic range compared with virological studies of hepatitis viruses among autopsy cases in Tokyo

    Microsoft Academic Search

    Masahiko Okudaira; Fumio Tsuda; Naoki Ikawa; Jun Takamatsu; Shogo Tokudome; Katsumi Kurosu; Makoto Mayumi

    2001-01-01

    Few reports exist comparing virological studies on hepatitis viruses with histopathological studies of autopsy cases other than those of liver clinics. Relations between hepatitis virus-related markers and hepatic histopathology were studied in 1044 autopsy cases (779 men and 265 women) at the Medical Examiner's Office, Tokyo. Heart blood was obtained at the autopsy, and the sera were submitted for virus-marker

  12. [Hepatic hemangioma: the choice of treatment].

    PubMed

    Aksenov, I V; Fedorchenko, A N

    2010-01-01

    117 patients with hepatic hemangioma were treated. 17 patients were operated on with the use of laser and plasmic scalpel. The possibility and technical features of liver resections by hepatic hemangiomas are discussed. In 8 of 17 operated patients, endovascular hemangiomatous vessel occlusion was effective. Authors state the necessity of reduction of surgical treatment of hepatic hemangiomas and substantiate the need of dynamic observation of such lesions of the liver. PMID:20559223

  13. Hepatic perfusion imaging: concepts and application.

    PubMed

    Haider, Masoom A; Farhadi, Farzin A; Milot, Laurent

    2010-08-01

    Hepatic perfusion imaging with magnetic resonance (MR) imaging is an emerging technique for quantitative assessment of diffuse hepatic disease and hepatic lesion blood flow. The principal method that has been used is based on T1 dynamic contrast-enhanced MR imaging. Perfusion imaging shows promise in the assessment of tumor therapy response, staging of liver fibrosis, and evaluation of hepatocellular carcinoma. The future standardization of imaging protocols and MR imaging pulse sequences will allow for broader clinical applications. PMID:21094450

  14. Rate Tornado Damage

    NSDL National Science Digital Library

    Tornadoes can produce damage that ranges from broken tree limbs to a block of houses swept from their foundations. They can inflict utter devastation across a wide swath of land or, destroy one house and leave others on either side largely untouched. In this interactive feature from NOVA Online, sudents examine a series of photos of tornado damage and assign intensity ratings (on the Fulita scale) based on what they see.

  15. Rate Tornado Damage

    NSDL National Science Digital Library

    Lexi Krock

    An interactive Flash animation that educates students about the Fujita scale for rating tornado wind speeds and the damage caused by tornados. After being presented with photographs of tornado damage, students are challenged to assign the tornado a rating on the F-scale. The interactive explains the different levels of the F-scale and provides instant feedback on whether or not the correct category was assigned to the tornado.

  16. Gene therapy for viral hepatitis.

    PubMed

    Gonzalez-Aseguinolaza, Gloria; Crettaz, Julien; Ochoa, Laura; Otano, Itziar; Aldabe, Rafael; Paneda, Astrid

    2006-12-01

    Hepatitis B and C infections are two of the most prevalent viral diseases in the world. Existing therapies against chronic viral hepatitis are far from satisfactory due to low response rates, undesirable side effects and selection of resistant viral strains. Therefore, new therapeutic approaches are urgently needed. This review, after briefly summarising the in vitro and in vivo systems for the study of both diseases and the genetic vehicles commonly used for liver gene transfer, examines the existing status of gene therapy-based antiviral strategies that have been employed to prevent, eliminate or reduce viral infection. In particular, the authors focus on the results obtained in clinical trials and experimental clinically relevant animal models. PMID:17223736

  17. Optimal treatment of hepatic encephalopathy.

    PubMed

    Waghray, A; Waghray, N; Kanna, S; Mullen, K

    2014-03-01

    Hepatic encephalopathy (HE) is a neuropsychiatric complication of acute or chronic liver disease with symptoms encompassing a continuum from mild confusion to coma. Both covert and overt HE have a significant impact on quality of life and healthcare related costs. The pathophysiology of HE is multifactorial and there is general consensus that ammonia and inflammation act synergistically to cause astrocyte swelling and cerebral edema. Current management strategies include the identification of precipitating factors and the initiation of pharmacologic therapies aimed at modulating intestinal flora and reducing levels of ammonia and other gut-derived toxins. Lactulose and rifaximin are two commonly used treatments for the management of HE. This article will review the optimal management of hepatic encephalopathy. PMID:24632768

  18. Fatal hepatic failure associated with graft rejection following reduced-intensity stem-cell transplantation for chronic idiopathic myelofibrosis (CIMF).

    PubMed

    Miyakoshi, Shigesaburo; Kami, Masahiro; Kishi, Yukiko; Murashige, Naoko; Yuji, Koichiro; Kusumi, Eiji; Matsumura, Tomoko; Onishi, Yasushi; Kobayashi, Kazuhiko; Kim, Sung-Won; Hamaki, Tamae; Takaue, Yoichi; Taniguchi, Shuichi

    2004-12-01

    A 54-year-old man with chronic idiopathic myelofibrosis (CIMF) underwent RIST. His clinical course had been uneventful until day 60, when splenomegaly reappeared. Hepatic dysfunction developed on day 75. Recipient-type hematopoiesis increased to 51% on day 90. After rapid tapering of cyclosporin, serum levels of AST and ALP normalized in parallel with recovery of complete chimerism on day 134. Yet, jaundice progressed. He died of liver failure on day 176. Postmortem examination revealed neither GVHD nor VOD. Graft rejection following RIST for CIMF may lead to fatal hepatic damage through extramedullary hematopoiesis in the liver or cytokine-mediated immune dysregulations. PMID:15621770

  19. Aquaporin4 in hepatic encephalopathy

    Microsoft Academic Search

    K. V. Rama Rao; M. D. Norenberg

    2007-01-01

    Brain edema is a critical component of hepatic encephalopathy (HE) associated with acute liver failure and such edema appears\\u000a to be principally due to astrocyte swelling (cytotoxic edema). Ammonia is believed to represent a major factor responsible\\u000a for astrocyte swelling, although the mechanisms by which ammonia causes such swelling are not completely understood. Recent\\u000a studies have implicated potential role of

  20. [Drug (statine)-induced hepatitis].

    PubMed

    Lazebnik, L B; Zvenigorodskaia, L A; Khomeriki, S G; Efremov, L I; Cherkashova, E A

    2009-01-01

    In the article is presented the case of development of medicinal hepatitis as result of irrational use of statin treatment at patient with Ischemic heart disease and nonalcoholic Fatty Liver Disease against morbid obesity. The clinical observation reflects the necessity of usage of liver protectors in prevention of possible side effects of hypolipidemic statin treatment and emphasizes the advantage of double cholesterol inhibition. PMID:19938288

  1. Chronic hepatitis C and steatosis

    Microsoft Academic Search

    Andrew D. Clouston; Julie R. Jonsson; Elizabeth E. Powell

    2004-01-01

    Steatosis is a common finding in chronic hepatitis C infection. It is associated with increased fibrogenesis and, in nongenotype\\u000a 3 infection, with a reduced response to antiviral therapy. The steatosis is multifactorial; host factors, particularly excess\\u000a body mass and insulin resistance, and viral cytopathic effects each play a variable role in different genotypes. How steatosis\\u000a or the accompanying metabolic changes

  2. Hepatic resection for hepatocellular carcinoma

    Microsoft Academic Search

    Masahiro Suenaga; Akimasa Nakao; Akio Harada; Toshiaki Nonami; Yoshikatsu Okada; Hayato Sugiura; Shinichi Uehara; Hiroshi Takagi

    1992-01-01

    One hundred and eighteen patients underwent hepatic resection for hepatocellular carcinoma from 1979 to 1987. Ninety-eight of these patients had co-existing cirrhosis of the liver; 18 patients underwent lobectomy, 28 patients had segmentectomy, and 52 patients had subsegmentectomy. In the 21 non-cirrhotic patients, 11 patients underwent lobectomy, 5 patients had segmentectomy, and 5 patients had subsegmentectomy. The operative mortality rate

  3. Ex vivo Analysis of Resident Hepatic Pro-inflammatory CD1d-reactive T cells & Hepatocyte Surface CD1d Expression in Hepatitis C

    PubMed Central

    Yanagisawa, Kazuhiko; Yue, Simon; van der Vliet, Hans J.; Wang, RuoJie; Alatrakchi, Nadia; Golden-Mason, Lucy; Schuppan, Detlef; Koziel, Margaret J.; Rosen, Hugo R.; Exley, Mark A.

    2013-01-01

    Hepatic CD1d-restricted and natural killer T cell populations are heterogeneous. Classical ‘Type 1’ ?-galactosylceramide-reactive CD1d-restricted T cells express ‘invariant’ TCR? (‘iNKT’). iNKT dominating rodent liver are implicated in inflammation, including in hepatitis models. Low levels of iNKT are detected in human liver, decreased in subjects with chronic hepatitis C (CHC). However, high levels of human hepatic CD161±CD56± non-invariant pro-inflammatory CD1d-restricted ‘Type 2’ T cells have been identified in vitro. Unlike rodents, healthy human hepatocytes only express trace and intracellular CD1d. Total hepatic CD1d appears to be increased in CHC and primary biliary cirrhosis. Direct ex vivo analysis of human intra-hepatic lymphocytes (IHL), including matched ex vivo versus in vitro expanded IHL, demonstrated detectable non-invariant CD1d-reactivity in substantial proportions of HCV-positive livers and significant fractions of HCV-negative livers. However, ?-galactosylceramide-reactive iNKT were detected only relatively rarely. Liver CD1d-restricted IHL produced IFN?, variable levels of IL-10, and modest levels of Th2 cytokines IL-4 and IL-13 ex vivo. In a novel FACS assay, a major fraction (10–20%) of hepatic T cells rapidly produced IFN? and up-regulated activation marker CD69 in response to CD1d. As previously only shown with murine iNKT, non-invariant human CD1d-specific responses were augmented by IL-12. Interestingly, CD1d was also found selectively expressed on the surface of hepatocytes in CHC, but not those CHC subjects with history of alcohol usage or resolved CHC. In contrast to hepatic iNKT, non-invariant IFN?-producing Type 2 CD1d-reactive NKT cells are commonly detected in CHC, together with cognate ligand CD1d, implicating them in CHC liver damage. PMID:23808994

  4. Hepatitis C in hemodialysis patients

    PubMed Central

    Marinaki, Smaragdi; Boletis, John N; Sakellariou, Stratigoula; Delladetsima, Ioanna K

    2015-01-01

    Despite reduction of hepatitis C prevalence after recognition of the virus and testing of blood products, hemodialysis (HD) patients still comprise a high risk group. The natural history of hepatitis C virus (HCV) infection in dialysis is not fully understood while the clinical outcome differs from that of the general population. HD patients show a milder liver disease with lower aminotransferase and viral levels depicted by milder histological features on liver biopsy. Furthermore, the “silent” clinical course is consistent with a slower disease progression and a lower frequency of cirrhosis and hepatocellular carcinoma. Potential explanations for the “beneficial” impact of uremia and hemodialysis on chronic HCV infection are impaired immunosurveillance leading to a less aggressive host response to the virus and intradialytic release of “hepatoprotective” cytokines such as interferon (IFN)-? and hepatocyte growth factor. However, chronic hepatitis C is associated with a higher liver disease related cardiovascular and all-cause mortality of HD patients. Therapy is indicated in selected patients groups including younger patients with low comorbidity burden and especially renal transplant candidates, preferably after performance of a liver biopsy. According to current recommendations, choice of treatment is IFN or pegylated interferon with a reported sustained viral response at 30%-40% and a withdrawal rate ranging from 17% to 30%. New data regarding combination therapy with low doses of ribavirin which provide higher standard variable rates and good safety results, offer another therapeutic option. The new protease inhibitors may be the future for HCV infected HD patients, though data are still lacking. PMID:25848478

  5. Hepatitis C virus and lymphoma.

    PubMed

    Viswanatha, D S; Dogan, A

    2007-12-01

    Hepatitis C virus (HCV) is well known for its aetiological role in chronic non-A, non-B viral hepatitis, liver cirrhosis and hepatocellular carcinoma; in addition, the virus has also been implicated in a number of extra-hepatic "autoimmune" disease manifestations. A causative association between HCV and non-Hodgkin lymphoma (NHL) was postulated relatively recently and has been the subject of intense investigation, as well as some debate. On the strength of epidemiological data, emerging biological investigations and clinical observations, HCV appears to be involved in the pathogenesis of at least a proportion of patients with NHL. Morphologically, HCV-associated lymphomas represent a variety of histological subtypes including marginal zone lymphoma (splenic, nodal and extranodal), small lymphocytic lymphoma/chronic lymphocytic leukaemia, lymphoplasmacytic lymphoma and diffuse large B-cell lymphoma. Remarkably, some HCV-associated NHL appears to be highly responsive to antiviral therapy, providing some clinical evidence for this relationship, as well as the prospect for novel therapeutic intervention. PMID:18042694

  6. [Steatosis and fibrosis: first stage of liver damage induced by chronic alcoholism. Our experience in 100 cases].

    PubMed

    Mancinella, A

    1991-04-15

    Having briefly analyzed the metabolism of ethanol in man, the author describes hepatocellular damage induced by alcohol abuse and histological, clinical and biohumoral features of steatosis and fibrosis. One hundred clinical cases of hepatic steatosis and fibrosis are also illustrated, studied and observed during five years. PMID:1828726

  7. Tissue Localization of Australia Antigen Immune Complexes in Acute and Chronic Hepatitis and Liver Cirrhosis

    PubMed Central

    Nowos?awski, Adam; Krawczy?ski, Krzysztof; Brzosko, Witold J.; Madali?ski, Kazimierz

    1972-01-01

    In a significant percentage of examined cases of fulminant hepatitis, subacute hepatitis, chronic aggressive hepatitis, liver cirrhosis and chronic persistent hepatitis, Australia (hepatitis-associated) antigen (Au HAA) was identified in the liver and in extrahepatic locations. The several immunofluorescent patterns of Au HAA localization in hepatocytes strongly suggested various stages of Au HAA accumulation and release. Deposits of a mixture of immunoglobulins G and M and occasionally ?1C-globulin were found in the cytoplasm of Au HAA containing hepatocytes, on their plasma membranes, on or in the nuclei, in the cytoplasm of Kupffer cells and, rarely, in the sinusoids. The accompanying tissue changes were hepatocellular degeneration and necrosis. These intra- and extracellular complexes of Au HAA and immunoglobulins displayed strong affinity for guinea pig complement in the immunohistochemical complement fixation reaction. When tested by immunodiffusion in agar, IgG dissociated from these complexes by potassium thiocyanate (KSCN) treatment showed anti-Au HAA specificity. In fulminant hepatitis neither Au HAA nor immunoglobulins and complement were found in the liver. In chronic aggressive hepatitis and subacute hepatitis the amount of the Au HAA immune complexes identified in the liver was approximately inversely proportional to the extent and severity of the parenchymal lesions. In liver cirrhosis and chronic persistent hepatitis there was a positive correlation between the amount of the Au HAA immune complexes found in the liver and the degree of hepatocellular damage. The deposits of Au HAA, identified in extrahepatic locations including germinal centers of lymph nodes and spleen, kidney glomeruli and blood vessel walls, were as a rule accompanied by deposits of IgG, IgM, ?1C-globulin and fibrin. All these deposits showed strong affinity for guinea pig complement in the immunohistochemical reaction of complement fixation. Germinal center activation, chronic membraneous glomerulonephritis, panarteritis and simple arteriolar hyalinosis were found at sites of localization of these deposits. ImagesFig 21Fig 22Fig 23Fig 24Fig 1Fig 2Fig 3Fig 4Fig 5Fig 6Fig 25Fig 26Fig 27Fig 28Fig 29Fig 7Fig 8Fig 9Fig 10Fig 11Fig 12Fig 13Fig 14Fig 15Fig 16Fig 17Fig 18Fig 19Fig 20 PMID:4628111

  8. Ipilimumab-associated Hepatitis: Clinicopathologic Characterization in a Series of 11 Cases.

    PubMed

    Johncilla, Melanie; Misdraji, Joseph; Pratt, Daniel S; Agoston, Agoston T; Lauwers, Gregory Y; Srivastava, Amitabh; Doyle, Leona A

    2015-08-01

    Ipilimumab is a monoclonal antibody that inhibits the CTLA4 receptor on cytotoxic T lymphocytes, resulting in immune-mediated tumor cell death. Ipilimumab is most often used in the treatment of metastatic melanoma, and rarely liver toxicity necessitating cessation of treatment occurs. The aim of this study was to characterize the histologic features and clinical course of ipilimumab-associated hepatitis. Eleven patients with clinical suspicion of ipilimumab-induced hepatitis, due to the development of abnormal liver function tests (LFTs) while receiving treatment, and who underwent liver biopsy, were identified over a 6-year period. Ten patients were male and 1 female (median age 58 y), and all received 1 to 4 doses of ipilimumab. None had known preexisting liver disease. Two patients were obese, and another had a history of alcohol abuse. Viral and autoimmune serologies were negative in all patients except 1 who had a mildly elevated ANA titer. Nine biopsies showed active hepatitis with 2 distinct histologic patterns: panlobular hepatitis in 6 cases and zone 3 hepatitis in 3. The inflammatory infiltrate was similar in composition in both patterns, composed predominantly of CD8 T lymphocytes, admixed histiocytes, scattered plasma cells, and eosinophils. Prominent histiocytic sinusoidal infiltrates were present in 7 cases and frequently formed loose histiocytic aggregates. Central vein endothelialitis was present in 8 cases. Patients in this group tended to have markedly elevated ALT, AST, and total bilirubin. Two cases did not fit into the above 2 histologic groups: 1 showed portal inflammation with cholangitis, and the other showed morphologic features indistinguishable from nonalcoholic steatohepatitis. Discontinuation of ipilimumab and administration of immunosuppressives resulted in resolution or marked improvement of LFTs in all patients within 3 months of presentation. Ipilimumab may potentially unmask previously subclinical liver disease, for example, fatty liver disease, and the diagnosis of ipilimumab-induced liver injury may only be recognized with certainty after cessation of the drug leads to normalization of LFTs. Overall, ipilimumab-associated hepatitis most often presents with a panlobular active hepatitis that resembles autoimmune hepatitis. Prominent sinusoidal histiocytic infiltrates and central vein damage with endothelialitis may be helpful histologic clues to the diagnosis of ipilimumab-associated hepatitis. PMID:26034866

  9. Hepatitis B antigens in serum and liver of chimpanzees acutely infected with hepatitis B virus.

    PubMed Central

    Berquist, K R; Peterson, J M; Murphy, B L; Ebert, J W; Maynard, J E; Purcell, R H

    1975-01-01

    We report the temporal patterns of various immunohistological and serological parameters of acute self-limited hepatitis B virus infection of two chimpanzees, and we provide evidence that the synthesis of hepatitis B core antigen precedes that of hepatitis B surface antigen. Our data suggest that existence of a biphasic hepatitis B virus infection involving a hematogenous reinfection of the liver and indicate that recruitment of liver cells to produce hepatitis B virus may occur in a pattern consistent with a replicative cycle of about 8 days. PMID:1100525

  10. Autoimmune Hepatitis Triggered by Treatment With Pegylated Interferon ?-2a and Ribavirin for Chronic Hepatitis C

    PubMed Central

    Pipaliya, Nirav; Choksi, Dhaval; Parikh, Pathik; Ingle, Meghraj; Sawant, Prabha

    2015-01-01

    Hepatitis flare is rarely observed during treatment with pegylated interferon alpha for hepatitis C virus (HCV) infection. A 49-year-old man receiving pegylated interferon ?-2a for HCV infection had icterus and hyperbiliru-binemia in the 14th week of therapy, with HCV RNA undetectable after the 12th dose. Liver biopsy was suggestive of chronic hepatitis with cirrhosis without interface pattern. Pegylated interferon was discontinued; a few weeks later, his aminotransferases and immunoglobulin levels increased significantly. Antibody to cytosolic liver antigen-1 was positive, and liver biopsy revealed lymphoplasmacytic infiltrate with intense interface hepatitis, consistent with autoimmune hepatitis.

  11. Anti-inflammatory effect of recombinant thrombomodulin for fulminant hepatic failure.

    PubMed

    Kurokohchi, Kazutaka; Imataki, Osamu; Kubo, Fumiyoshi

    2015-07-14

    Fulminant hepatic failure (FHF) is a critical illness that can be comorbid to primary liver damage. FHF shows a high mortality rate, and patients with FHF require intensive therapy, including plasma apheresis. However, intensive care at the present is not enough to restore the severe liver damage or promote hepatocellular reproduction, and a standard therapy for the treatment of FHF has not been established. An 86-year-old female with FHF was admitted to our hospital. Her manifestation demonstrated a clinical situation of systemic inflammatory response syndrome (SIRS) and disseminated intravascular coagulation. A diagnosis of fulminant hepatitis was made according to the definition given in the position paper of the American Association for the Study of Liver Diseases. Her serum hepatocyte growth factor (HGF) level had increased to 11.84 ng/mL. The HGF level indicated massive liver damage as seen in FHF. Recombinant thrombomodulin (rTM) was administered daily from the admission day for 1 wk at 380 U/kg. The patient's white blood cells and C-reactive protein responded to the rTM treatment within a few days. The HGF level and PT recovered to the normal range. The levels of proinflammatory cytokines (tumor necrosis factor-? and interleukin-1?) were suppressed by the administration of rTM. The patient's hepatic function (e.g., PT and albumin) completely recovered without plasma exchange. rTM may modulate the over-response of SIRS with the improvement of proinflammatory cytokines. The underlying mechanism is thought to be the inhibitory effect of rTM on high-mobility group box 1 (HMBG1). The pathogenesis of HMBG1 protein in fulminant hepatic failure has been already known. A novel favorable effect of rTM for SIRS would be promising for FHF, and the wide application of rTM for SIRS should be considered. PMID:26185395

  12. Anti-inflammatory effect of recombinant thrombomodulin for fulminant hepatic failure

    PubMed Central

    Kurokohchi, Kazutaka; Imataki, Osamu; Kubo, Fumiyoshi

    2015-01-01

    Fulminant hepatic failure (FHF) is a critical illness that can be comorbid to primary liver damage. FHF shows a high mortality rate, and patients with FHF require intensive therapy, including plasma apheresis. However, intensive care at the present is not enough to restore the severe liver damage or promote hepatocellular reproduction, and a standard therapy for the treatment of FHF has not been established. An 86-year-old female with FHF was admitted to our hospital. Her manifestation demonstrated a clinical situation of systemic inflammatory response syndrome (SIRS) and disseminated intravascular coagulation. A diagnosis of fulminant hepatitis was made according to the definition given in the position paper of the American Association for the Study of Liver Diseases. Her serum hepatocyte growth factor (HGF) level had increased to 11.84 ng/mL. The HGF level indicated massive liver damage as seen in FHF. Recombinant thrombomodulin (rTM) was administered daily from the admission day for 1 wk at 380 U/kg. The patient’s white blood cells and C-reactive protein responded to the rTM treatment within a few days. The HGF level and PT recovered to the normal range. The levels of proinflammatory cytokines (tumor necrosis factor-? and interleukin-1?) were suppressed by the administration of rTM. The patient’s hepatic function (e.g., PT and albumin) completely recovered without plasma exchange. rTM may modulate the over-response of SIRS with the improvement of proinflammatory cytokines. The underlying mechanism is thought to be the inhibitory effect of rTM on high-mobility group box 1 (HMBG1). The pathogenesis of HMBG1 protein in fulminant hepatic failure has been already known. A novel favorable effect of rTM for SIRS would be promising for FHF, and the wide application of rTM for SIRS should be considered. PMID:26185395

  13. Hepatic histology in hepatitis C virus carriers coinfected with hepatitis G virus

    PubMed Central

    Petrik, J; Guella, L; Wight, D; Pearson, G; Hinton, J; Parker, H; Allain, J; Alexander, G

    1998-01-01

    Background—A novel flavivirus has been described recently and designated hepatitis G virus (HGV). The virus is transmitted by the parenteral route but it is uncertain whether it is associated with chronic liver disease because liver biopsy is difficult to justify in this group. ?Aims—To examine histological features of liver biopsy in patients infected with hepatitis C virus (HCV) according to the presence or absence of HCV and HGV RNA. ?Methods—One hundred and thirty one consecutive HCV carriers undergoing staging liver biopsy were studied retrospectively. In each, HCV RNA and HGV RNA were detected by reverse transcription polymerase chain reaction on serum samples collected at the time of biopsy. The presence of each RNA was correlated with histological features blind to the RNA results; individual histological features of inflammation or fibrosis were scored separately. ?Results—Nineteen patients were positive for both HGV and HCV RNA in serum, 91 were positive for HCV RNA alone, two were positive for HGV RNA alone, and 19 were negative for both RNA species. Neither age nor sex differed between the groups; a greater proportion of intravenous drug users were HGV RNA positive, but this was not statistically significant. There was no effect of HGV coinfection on the stage of fibrosis or any other histological parameter except steatosis; patients with HCV and HGV RNA had a higher mean score for fat than those patients with HCV RNA alone (p<0.05). ?Conclusions—HGV coinfection has no important effects on histological features in chronic HCV carriers. It is unlikely that HGV infection causes chronic liver disease. ?? Keywords: hepatitis C virus; hepatitis G virus; RNA; histology PMID:9505894

  14. Yeast-recombinant hepatitis B vaccine: efficacy with hepatitis B immune globulin in prevention of perinatal hepatitis B virus transmission

    SciTech Connect

    Stevens, C.E.; Taylor, P.E.; Tong, M.J.; Toy, P.T.; Vyas, G.N.; Nair, P.V.; Weissman, J.Y.; Krugman, S.

    1987-05-15

    A yeast-recombinant hepatitis B vaccine was licensed recently by the Food and Drug administration and is now available. To assess the efficacy of the yeast-recombinant vaccine, the authors administered the vaccine in combination with hepatitis B immune globulin to high-risk newborns. If infants whose mothers were positive for both hepatitis B surface antigen and the e antigen receive no immunoprophylaxis, 70% to 90% become infected with the virus, and almost all become chronic carriers. Among infants in this study who received hepatitis B immune globulin at birth and three 5-/sup +/g doses of yeast-recombinant hepatitis B vaccine, only 4.8% became chronic carriers, a better than 90% level of protection and a rate that is comparable with that seen with immune globulin and plasma-derived hepatitis B vaccine. Hepatitis surface antigen and antibodies were detected by radioimmunoassay. These data suggest that, in this high-risk setting, the yeast-recombinant vaccine is as effective as the plasma-derived vaccine in preventing hepatitis B virus infection and the chronic carrier state.

  15. Is hepatitis A more severe in patients with chronic hepatitis B and other chronic liver diseases?

    PubMed

    Keeffe, E B

    1995-02-01

    There are several published case series of acute hepatitis A, with coverage ranging from epidemics to case reports, that provide information regarding the clinical course and outcome of hepatitis A in patients with underlying chronic hepatitis B virus (HBV) infection (1-12). Only a few reports have addressed the outcome of hepatitis A in patients with other chronic liver diseases (2, 13). Some, but not all, of these reports suggest that hepatitis A superimposed on chronic hepatitis B or other chronic liver diseases is associated with higher peak laboratory abnormalities, more severe disease, including fulminant hepatic failure, and a higher case fatality rate. In addition, analysis of HBsAg titer and serum markers of HBV replication, including HBeAg, HBV DNA, and DNA polymerase, reveals suppression of HBV replication. With the availability of hepatitis A virus (HAV) vaccine in many countries and its imminent approval for use in the United States, the issue of whether or not patients with chronic liver diseases, including chronic HBV infection, should be a target group for vaccination to prevent hepatitis A warrants consideration. The purpose of this review is to analyze the published literature addressing the clinical course and outcome of acute hepatitis A in patients with chronic HBV infection and other chronic liver diseases to determine if hepatitis A is more severe in these patients. PMID:7847285

  16. Reducing Radiation Damage

    SciTech Connect

    Blankenbecler, Richard

    2006-06-05

    This talk describes the use of a modified treatment sequence, i.e., radiation dose, geometry, dwell time, etc., to mitigate some of the deleterious effects of cancer radiotherapy by utilizing natural cell repair processes. If bad side effects can be reduced, a more aggressive therapy can be put into place. Cells contain many mechanisms that repair damage of various types. If the damage can not be repaired, cells will undergo apoptosis (cell death). Data will be reviewed that support the fact that a small dose of radiation will activate damage repair genes within a cell. Once the mechanisms are fully active, they will efficiently repair the severe damage from a much larger radiation dose. The data ranges from experiments on specific cell cultures using microarray (gene chip) techniques to experiments on complete organisms. The suggested effect and treatment is consistent with the assumption that all radiation is harmful, no matter how small the dose. Nevertheless, the harm can be reduced. These mechanisms need to be further studied and characterized. In particular, their time dependence needs to be understood before the proposed treatment can be optimized. Under certain situations it is also possible that the deleterious effects of chemotherapy can be mitigated and the damage to radiation workers can be reduced.

  17. Hepatic function and the cardiometabolic syndrome.

    PubMed

    Wiernsperger, Nicolas

    2013-01-01

    Despite skeletal muscle being considered by many as the source of insulin resistance, physiology tells us that the liver is a central and cardinal regulator of glucose homeostasis. This is sometimes underestimated because, in contrast with muscle, investigations of liver function are technically very difficult. Nevertheless, recent experimental and clinical research has demonstrated clearly that, due in part to its anatomic position, the liver is exquisitely sensitive to insulin and other hormonal and neural factors, either by direct intrahepatic mechanisms or indirectly by organ cross-talk with muscle or adipose tissue. Because the liver receives absorbed nutrients, these have a direct impact on liver function, whether via a caloric excess or via the nature of food components (eg, fructose, many lipids, and trans fatty acids). An emerging observation with a possibly great future is the increase in intestinal permeability observed as a consequence of high fat intake or bacterial modifications in microbiota, whereby substances normally not crossing the gut gain access to the liver, where inflammation, oxidative stress, and lipid accumulation leads to fatty liver, a situation observed very early in the development of diabetes. The visceral adipose tissue located nearby is another main source of inflammatory substances and oxidative stress, and also acts on hepatocytes and Kupffer cells, resulting in stimulation of macrophages. Liberation of these substances, in particular triglycerides and inflammation factors, into the circulation leads to ectopic fat deposition and vascular damage. Therefore, the liver is directly involved in the development of the prediabetic cardiometabolic syndrome. Treatments are mainly metformin, and possibly statins and vitamin D. A very promising avenue is treatment of the leaky gut, which appears increasingly to be an important causal factor in hepatic insulin resistance and steatosis. PMID:24143116

  18. Potential mechanisms of hepatitis B virus induced liver injury.

    PubMed

    Suhail, Mohd; Abdel-Hafiz, Hany; Ali, Ashraf; Fatima, Kaneez; Damanhouri, Ghazi A; Azhar, Esam; Chaudhary, Adeel Ga; Qadri, Ishtiaq

    2014-09-21

    Chronic active hepatitis (CAH) is acknowledged as an imperative risk factor for the development of liver injury and hepatocellular carcinoma. The histological end points of CAH are chronic inflammation, fibrosis and cirrhosis which are coupled with increased DNA synthesis in cirrhotic vs healthy normal livers. The potential mechanism involved in CAH includes a combination of processes leading to liver cell necrosis, inflammation and cytokine production and liver scaring (fibrosis). The severity of liver damage is regulated by Hepatitis B virus genotypes and viral components. The viral and cellular factors that contribute to liver injury are discussed in this article. Liver injury caused by the viral infection affects many cellular processes such as cell signaling, apoptosis, transcription, DNA repair which in turn induce radical effects on cell survival, growth, transformation and maintenance. The consequence of such perturbations is resulted in the alteration of bile secretion, gluconeogenesis, glycolysis, detoxification and metabolism of carbohydrates, proteins, fat and balance of nutrients. The identification and elucidation of the molecular pathways perturbed by the viral proteins are important in order to design effective strategy to minimize and/or restore the hepatocytes injury. PMID:25253946

  19. Potential mechanisms of hepatitis B virus induced liver injury

    PubMed Central

    Suhail, Mohd; Abdel-Hafiz, Hany; Ali, Ashraf; Fatima, Kaneez; Damanhouri, Ghazi A; Azhar, Esam; Chaudhary, Adeel GA; Qadri, Ishtiaq

    2014-01-01

    Chronic active hepatitis (CAH) is acknowledged as an imperative risk factor for the development of liver injury and hepatocellular carcinoma. The histological end points of CAH are chronic inflammation, fibrosis and cirrhosis which are coupled with increased DNA synthesis in cirrhotic vs healthy normal livers. The potential mechanism involved in CAH includes a combination of processes leading to liver cell necrosis, inflammation and cytokine production and liver scaring (fibrosis). The severity of liver damage is regulated by Hepatitis B virus genotypes and viral components. The viral and cellular factors that contribute to liver injury are discussed in this article. Liver injury caused by the viral infection affects many cellular processes such as cell signaling, apoptosis, transcription, DNA repair which in turn induce radical effects on cell survival, growth, transformation and maintenance. The consequence of such perturbations is resulted in the alteration of bile secretion, gluconeogenesis, glycolysis, detoxification and metabolism of carbohydrates, proteins, fat and balance of nutrients. The identification and elucidation of the molecular pathways perturbed by the viral proteins are important in order to design effective strategy to minimize and/or restore the hepatocytes injury. PMID:25253946

  20. Pharmacotherapy of acute alcoholic hepatitis in clinical practice

    PubMed Central

    Abenavoli, Ludovico; Milic, Natasa; Rouabhia, Samir; Addolorato, Giovanni

    2014-01-01

    Severe alcoholic hepatitis (AH) is an acute form of alcohol induced liver disease with a poor prognosis that is seen in the patients who consume large quantities of alcohol. The diagnosis of AH is based on the appropriate alcohol intake history and is supported with clinical and histological features, and several scoring systems. Glucocorticoids are the mainstay for treating severe AH with pentoxifylline used as an alternative to steroids in addition to total alcohol abstinence. Liver transplantation is a possible therapeutic option for severe AH. Among the anti-craving medications able to improve abstinence rate, baclofen seems to be effective and safe in the alcoholic patients affected by severe liver damage. PMID:24605014

  1. Damage Tolerance Assessment Branch

    NASA Technical Reports Server (NTRS)

    Walker, James L.

    2013-01-01

    The Damage Tolerance Assessment Branch evaluates the ability of a structure to perform reliably throughout its service life in the presence of a defect, crack, or other form of damage. Such assessment is fundamental to the use of structural materials and requires an integral blend of materials engineering, fracture testing and analysis, and nondestructive evaluation. The vision of the Branch is to increase the safety of manned space flight by improving the fracture control and the associated nondestructive evaluation processes through development and application of standards, guidelines, advanced test and analytical methods. The Branch also strives to assist and solve non-aerospace related NDE and damage tolerance problems, providing consultation, prototyping and inspection services.

  2. Occult Viral Hepatitis and Noncirrhotic Hepatocellular Carcinoma

    Microsoft Academic Search

    Stuart C. Gordon

    2005-01-01

    The achievement of a sustained virologic response to hepatitis C antiviral therapy represents a milestone occurrence that many tout as a cure. Recent studies, however, have found trace HCV viral material both among sustained responders and in patients with chronic liver disease who are HCV RNA negative, suggesting the entity of occult hepatitis C. As a body of literature emerges

  3. [Human immunodeficiency virus infection and viral hepatitis].

    PubMed

    Soriano, Vicente; Martin-Carbonero, Luz; Vispo, Eugenia; Labarga, Pablo; Barreiro, Pablo

    2011-11-01

    Hepatic complications currently represent one of the leading reasons for medical consultations, hospitalisation, and death in the HIV-infected population. This is due to a large extent to viral hepatitis, given its disproportionate frequency in this population. Chronic hepatitis B affects 5-10% of the HIV-infected population. Vaccination has reduced the incidence of liver disease related to hepatitis-B virus (HBV), and the availability of tenofovir has dramatically improved the prognosis of HIV/HBV carriers. Delta hepatitis affects around 15% of HIV-infected individuals in Europe harbouring positive HBsAg. It has the worst prognosis, given its accelerated course to cirrhosis and the absence of successful therapy. Lastly, chronic hepatitis C is the major cause of liver disease in the HIV population. Although classically linked to persons infected parenterally (i.e., intravenous drug users), outbreaks of acute hepatitis C among homosexual men have been reported over the last decade. Treatment with pegylated interferon plus ribavirin provides a cure in less than 40% of patients. However, the introduction of new direct acting antivirals against hepatitis- C virus (HCV) (telaprevir, boceprevir) has revolutionised the field, as HAART did in 1996 in the HIV field, improving the prognosis of co-infected patients. However, interactions between these drugs and antiretroviral agents and the risk of selective resistance pose huge threats in this population. PMID:21978797

  4. Neurobehavioral Correlates of Chronic Hepatitis C

    Microsoft Academic Search

    Robin C. Hilsabeck; Parviz Malek-Ahmadi

    2004-01-01

    Chronic infection with the hepatitis C virus is a major public health concern in the United States and worldwide, and persons with psychiatric histories are more likely to have chronic hepatitis C (CHC). Neurobehavioral consequences of CHC are common in all phases of the disease process and significantly contribute to morbidity. Antiviral treatment also is associated with neurobehavioral difficulties that

  5. Hazards of hepatitis at the Hajj.

    PubMed

    Rafiq, Shafquat M; Rashid, Harunor; Haworth, Elizabeth; Booy, Robert

    2009-07-01

    While an increased risk of hepatitis is associated with travel, the risk of hepatitis associated with the Islamic Hajj pilgrimage to Mecca, Saudi Arabia has not been carefully quantified. Conditions unique to this gathering can pose the risk of both enteral and parenteral viral hepatitis. During this congregation, pilgrims stay in tents shared by 100 or more people often living on foods from street vendors and sharing common toilet facilities that can expose them to both hepatitis A and E. To mark the end of the festival, head shaving or trimming by fellow pilgrims or street barbers, who often re-use their razor may expose them to hepatitis B or C. Pilgrims are also at risk of cuts to the hands and feet while sacrificing cattle and walking barefooted, which may further increase the risk of parenteral viral hepatitis. Emerging diseases such as Alkhumra virus and Rift Valley fever, which may cause hepatitis, are also potentially important for the Hajj pilgrims. Improved health education to increase awareness about the risk of these diseases and appropriate immunisations, particularly hepatitis A and B vaccines, could play an important role. PMID:19717108

  6. Review Future therapies for hepatitis C

    Microsoft Academic Search

    Jean-Michel Pawlotsky; Robert G Gish

    Although pegylated interferon-? plus ribavirin has become the standard for treating chronic hepatitis C virus infection, a substantial number of patients do not tolerate therapy and require dose reduction or discontin- uation, or do not respond to this combination therapy. Thus, new therapeutic options are needed. An increased knowledge of the hepatitis C virus and an understanding of its replication

  7. Hepatitis C: molecular virology and antiviral targets

    Microsoft Academic Search

    Darius Moradpour; Volker Brass; Rainer Gosert; Benno Wölk; Hubert E. Blum

    2002-01-01

    Chronic hepatitis C is a leading cause of liver cirrhosis and hepatocellular carcinoma worldwide. Although current treatment options are limited, progress in understanding the molecular virology of hepatitis C has led to the identification of novel antiviral targets. Moreover, in vitro and in vivo model systems have been developed that allow systematic evaluation of new therapeutic strategies. This review details

  8. Guillain-Barré syndrome following hepatitis E

    Microsoft Academic Search

    Jean Philippe Loly; Estelle Rikir; Maxime Seivert; Emile Legros; Pierre Defrance; Jacques Belaiche; Gustave Moonen; Jean Delwaide

    2009-01-01

    Guillain-Barré syndrome (GBS) is often triggered by a preceding bacterial or viral infection. Occasionally, it has been observed in association with acute hepatitis A, B and C, and three cases have been previously described in India in which GBS was associated with acute hepatitis E. A molecular mimicry mechanism is supposed to be involved in the pathogenesis of GBS triggered

  9. Chronic hepatitis in Doberman pinschers. A review

    Microsoft Academic Search

    P. J. J. Mandigers; T. S. G. A. M. van den Ingh; B. Spee; L. C. Penning; P. Bode; J. Rothuizen

    2004-01-01

    Chronic hepatitis in Doberman pinschers is predominantly seen in female dogs, usually between 4 and 7 years of age and was first recognized in the early eighties. The histopathological characteristics of Doberman hepatitis are those of micronodular cirrhosis with histological features of fibrosis, piece meal necrosis and progressive lymphocyte and plasma cell infiltration of the portal triads. Currently there are

  10. "Hepatitis" - Prevention and management in dental practice.

    PubMed

    Dahiya, Parveen; Kamal, Reet; Sharma, Varun; Kaur, Saravpreet

    2015-01-01

    Today, viral hepatitis has become a silent epidemic worldwide. It is the major cause of liver cirrhosis and liver carcinoma. In a dental office, infections can be expedited through several routes, including direct or indirect contact with blood, oral fluids, droplet splatter, aerosols, etc. The aim of the present review is to increase the awareness among dental practitioners, so as to reduce the burden of hepatitis in their community. Electronic databases like PubMed, Medline, ProQuest, etc. were searched using the keywords hepatitis, dentist, liver disease, and infection control. Manual search of various journals and books was also carried out. Only highly relevant articles from English literature were considered for the present review. The results revealed that the dentists were among the high-risk groups for hepatitis, and they have little information on the factors associated with adherence to hepatitis B vaccination. A dentist can play a major role in the prevention of hepatitis by considering each and every patient as a potential carrier of hepatitis. Proper infection control, sterilization, and prophylactic vaccination protocols should be followed in order to reduce the risk of hepatitis. PMID:26097847

  11. ALLYLISOPROPYLACETAMIDE INDUCES RAT HEPATIC ORNITHINE DECARBOXYLASE

    EPA Science Inventory

    In rat liver, allylisopropylacetamide (AIA) treatment strongly induced (25-fold) the activity of rat hepatic ornithine decarboxylase (ODC). y either the oral or the subcutaneous routes, AIA produced a long-lasting induction (30 to 4O hours) of hepatic ODC activity. hree analogs o...

  12. Hepatitis” – Prevention and management in dental practice

    PubMed Central

    Dahiya, Parveen; Kamal, Reet; Sharma, Varun; Kaur, Saravpreet

    2015-01-01

    Today, viral hepatitis has become a silent epidemic worldwide. It is the major cause of liver cirrhosis and liver carcinoma. In a dental office, infections can be expedited through several routes, including direct or indirect contact with blood, oral fluids, droplet splatter, aerosols, etc. The aim of the present review is to increase the awareness among dental practitioners, so as to reduce the burden of hepatitis in their community. Electronic databases like PubMed, Medline, ProQuest, etc. were searched using the keywords hepatitis, dentist, liver disease, and infection control. Manual search of various journals and books was also carried out. Only highly relevant articles from English literature were considered for the present review. The results revealed that the dentists were among the high-risk groups for hepatitis, and they have little information on the factors associated with adherence to hepatitis B vaccination. A dentist can play a major role in the prevention of hepatitis by considering each and every patient as a potential carrier of hepatitis. Proper infection control, sterilization, and prophylactic vaccination protocols should be followed in order to reduce the risk of hepatitis.

  13. Radioimmunoassay for hepatitis B core antigen

    SciTech Connect

    Sagnelli, E. (Mount Sinai School of Medicine of the City Univ. of New York); Pereira, C.; Triolo, G.; Vernace, S.; Paronetto, F.

    1982-02-01

    Serum hepatitis B core antigen (HBcAg) is an important marker of hepatitis B virus replication. We describe an easy, sensitive radioimmunoassay for determination of HBcAg in detergent-treated serum pellets containing Dane particles. Components of a commercial kit for anticore determination are used, and HBcAG is measured by competitive inhibition of binding of /sub 125/I-labeled antibodies to HBcAg with HBcAg-coated beads. We assayed for HBcAG in the sera of 49 patients with hepatitis B surface antigen (HBsAg)-positive chronic hepatitis, 50 patients with HBsAg-negative chronic hepatitis, and 30 healthy volunteers. HBcAg was detected in 41% of patients with HBsAg-positive chronic hepatitis but not in patients with HBsAg-negative chronic hepatitis. Hepatitis Be antigen (an antigen closely associated with the core of Dane particles) determined in the same sera by radioimmunoassay, was not detected in 50% of HBcAg-positive sera.

  14. Damage Control Orthopaedics

    Microsoft Academic Search

    Julie M. Keller; Andrew N. Pollak

    \\u000a University of Maryland School of Medicine\\u000a \\u000a Julie M. Keller MD, Andrew N. Pollak MD\\u000a \\u000a \\u000a In damage control for trauma patients, the main tenets are to perform temporary operative procedures to provide time for physiologic\\u000a stabilization before definitive surgical care. There are four distinct phases of the damage control philosophy: the first\\u000a is recognition of the at risk patient; next, temporizing

  15. Sofosbuvir for treatment of chronic hepatitis C.

    PubMed

    Kattakuzhy, Sarah; Levy, Rachel; Kottilil, Shyam

    2015-04-01

    Chronic hepatitis C is a leading cause of liver-related morbidity and mortality worldwide. If untreated, chronic hepatitis C can progress to advanced liver fibrosis, cirrhosis, liver failure, hepatocellular carcinoma and death. Until recently, treatment of hepatitis C predominantly constituted an immunomodulatory agent, peg-interferon-alfa and ribavirin. In 2011, the first class of directly acting antiviral agents, HCV NS3/4A serine protease inhibitors, was added to peg-interferon-alfa and ribavirin with increased efficacy. In the past year, an NS5B inhibitor, sofosbuvir, has emerged as a potent agent with pangenotypic efficacy, resulting in the first interferon-free regimen for the treatment of hepatitis C. This review summarizes the data that resulted in regulatory approval of sofosbuvir and highlights the future of hepatitis C therapy with sofosbuvir as the backbone of a highly effective antiviral regimen. PMID:25788194

  16. Haemorrhagic rupture of hepatic simple cysts.

    PubMed

    Simon, Tiarah; Bakker, Ilsalien S; Penninga, Luit; Nellensteijn, David R

    2015-01-01

    Haemorrhagic rupture is a life-threatening complication of a hepatic simple cyst. A 63-year-old man presented with severe acute abdominal pain and a massive haemoperitoneum resulting from haemorrhagic rupture of a large hepatic cyst. The haemorrhagic rupture was aggravated by an overdose of vitamin K-antagonist treatment. CT scans revealed a large hepatic simple cyst. The patient was successfully treated conservatively with resuscitation, transfusion therapy and administration of coagulation agents. To date, there is no clear evidence regarding optimal treatment of haemorrhagic hepatic cyst rupture. The risk of recurrent bleeding from the haemorrhagic hepatic simple cyst, and the need for final treatment to avoid rebleeding either by percutaneous sclerotherapy, endovascular embolisation, surgical cyst resection, or surgical deroofing, is discussed. PMID:25697302

  17. NDRG2 Ameliorates Hepatic Fibrosis by Inhibiting the TGF-?1\\/Smad Pathway and Altering the MMP2\\/TIMP2 Ratio in Rats

    Microsoft Academic Search

    Jiandong Yang; Jin Zheng; Lin Wu; Ming Shi; Hongtao Zhang; Xing Wang; Ning Xia; Desheng Wang; Xinping Liu; Libo Yao; Yan Li; Kefeng Dou

    2011-01-01

    Liver fibrosis is a worldwide clinical issue. It has been well established that activated hepatic stellate cells (HSCs) are responsible for excessive extracellular matrix (ECM) deposition in chronically damaged livers. The identification of key elements that control HSCs activation will help to further our understanding of liver fibrosis and improve the outcome of clinical treatment. This study demonstrates that N-Myc

  18. Hepatic resection under selective portal vein occlusion using degradable starch microspheres. A simple procedure of an experimental study using the pig.

    PubMed

    Ezaki, T; Yamaguchi, H; Sasaki, Y; Ishida, T; Fujiwara, M

    2001-01-01

    A simple technique is described to perform hepatectomy. The technique consists of portal vein blood flow occlusion using degradable starch microspheres injected through an ultrasonically-guided puncture at the point of resection root and hepatic artery occlusion. The method minimizes ischemic damage to the liver remnant and is easy to perform. PMID:11268939

  19. THE PREVALENCE OF VIRAL HEPATITIS AMONG THE HMONG PEOPLE OF NORTHERN THAILAND

    Microsoft Academic Search

    S Louisirirotchanakul; KSA Myint; B Srimee; C Kanoksinsombat; C Khamboonruang; P Kunstadter; Chantapong Wasi

    Sera from 269 Hmong people (102 males and 167 females, with mean age 35.4 years, range 16-63 years) were examined in order to determine the seroprevalence of hepatitis virus infection. The seroprevalence rates for HAV (hepatitis A virus), HBV (hepatitis B virus), HCV (hepatitis C virus), HDV (hepatitis D virus), HEV (hepatitis E virus), HGV (hepatitis G virus) and TTV

  20. Best Pract Res Clin Gastroenterol . Author manuscript Diagnosis and management of chronic viral hepatitis: antigens, antibodies

    E-print Network

    Paris-Sud XI, Université de

    of chronic viral hepatitis: antigens, antibodies and viral genomes St phane Chevaliezé 1 2 , Jean ; Hepatitis B Antibodies ; blood ; Hepatitis B Antigens ; blood ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; diagnosis ; drug therapy ; genetics ; Hepatitis C Antibodies ; blood ; Hepatitis C