Sample records for acute alcoholic hepatitis

  1. Hemolysis in Acute Alcoholic Hepatitis: Zieve's Syndrome

    PubMed Central

    Sitrin, Michael

    2015-01-01

    A 45-year-old man presented with acute alcoholic hepatitis, jaundice, and anemia on admission. There was no history of bleeding or any evidence of gastrointestinal blood loss. Lab studies revealed hemolysis as the cause of anemia. The patient was diagnosed with Zieve's syndrome and managed with supportive measures. He recovered well and was discharged to a detoxification unit in a stable condition. Zieve's syndrome has been described in literature, mostly in non-English language case studies, but is largely under-recognized and under-reported. Diagnosis should be made quickly to avoid unnecessary invasive diagnostic interventions.

  2. 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

  3. Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: An Italian position statement

    PubMed Central

    Testino, Gianni; Burra, Patrizia; Bonino, Ferruccio; Piani, Francesco; Sumberaz, Alessandro; Peressutti, Roberto; Giannelli Castiglione, Andrea; Patussi, Valentino; Fanucchi, Tiziana; Ancarani, Ornella; De Cerce, Giovanna; Iannini, Anna Teresa; Greco, Giovanni; Mosti, Antonio; Durante, Marilena; Babocci, Paola; Quartini, Mariano; Mioni, Davide; Aricò, Sarino; Baselice, Aniello; Leone, Silvia; Lozer, Fabiola; Scafato, Emanuele; Borro, Paolo

    2014-01-01

    Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the “6-mo rule”. Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The “Group of Italian Regions” suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups. PMID:25356027

  4. 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.

  5. Serum Metabolomic Profiling in Acute Alcoholic Hepatitis Identifies Multiple Dysregulated Pathways

    PubMed Central

    Rachakonda, Vikrant; Gabbert, Charles; Raina, Amit; Bell, Lauren N.; Cooper, Sara; Malik, Shahid; Behari, Jaideep

    2014-01-01

    Background and Objectives While animal studies have implicated derangements of global energy homeostasis in the pathogenesis of acute alcoholic hepatitis (AAH), the relevance of these findings to the development of human AAH remains unclear. Using global, unbiased serum metabolomics analysis, we sought to characterize alterations in metabolic pathways associated with severe AAH and identify potential biomarkers for disease prognosis. Methods This prospective, case-control study design included 25 patients with severe AAH and 25 ambulatory patients with alcoholic cirrhosis. Serum samples were collected within 24 hours of the index clinical encounter. Global, unbiased metabolomics profiling was performed. Patients were followed for 180 days after enrollment to determine survival. Results Levels of 234 biochemicals were altered in subjects with severe AAH. Random-forest analysis, principal component analysis, and integrated hierarchical clustering methods demonstrated that metabolomics profiles separated the two cohorts with 100% accuracy. Severe AAH was associated with enhanced triglyceride lipolysis, impaired mitochondrial fatty acid beta oxidation, and upregulated omega oxidation. Low levels of multiple lysolipids and related metabolites suggested decreased plasma membrane remodeling in severe AAH. While most measured bile acids were increased in severe AAH, low deoxycholate and glycodeoxycholate levels indicated intestinal dysbiosis. Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA) cycle activity, and enhanced peptide catabolism. Finally, altered levels of small molecules related to glutathione metabolism and antioxidant vitamin depletion were observed in patients with severe AAH. Univariable logistic regression revealed 15 metabolites associated with 180-day survival in severe AAH. Conclusion Severe AAH is characterized by a distinct metabolic phenotype spanning multiple pathways. Metabolomics profiling revealed a panel of biomarkers for disease prognosis, and future studies are planned to validate these findings in larger cohorts of patients with severe AAH. PMID:25461442

  6. 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

  7. 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

  8. Acute alcohol intoxication.

    PubMed

    Vonghia, Luisa; Leggio, Lorenzo; Ferrulli, Anna; Bertini, Marco; Gasbarrini, Giovanni; Addolorato, Giovanni

    2008-12-01

    Acute alcohol intoxication is a clinically harmful condition that usually follows the ingestion of a large amount of alcohol. Clinical manifestations are heterogeneous and involve different organs and apparatuses, with behavioral, cardiac, gastrointestinal, pulmonary, neurological, and metabolic effects. The management of an intoxicated patient occurs mainly in the emergency department and is aimed at stabilizing the clinical condition of the patient, depending on his/her clinical presentation. One specific drug that is useful in the treatment of acute alcohol intoxication is metadoxine, which is able to accelerate ethanol excretion. In patients presenting an acute alcohol intoxication, alcohol-related disorders should be detected so that the patient can be directed to an alcohol treatment unit, where a personalized, specific treatment can be established. PMID:19046719

  9. 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.

  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. [The catalase inhibitor aminotriazole alleviates acute alcoholic liver injury].

    PubMed

    Ai, Qing; Ge, Pu; Dai, Jie; Liang, Tian-Cai; Yang, Qing; Lin, Ling; Zhang, Li

    2015-02-25

    In this study, the effects of catalase (CAT) inhibitor aminotriazole (ATZ) on alcohol-induced acute liver injury were investigated to explore the potential roles of CAT in alcoholic liver injury. Acute liver injury was induced by intraperitoneal injection of alcohol in Sprague Dawley (SD) rats, and various doses of ATZ (100-400 mg/kg) or vehicle were administered intraperitoneally at 30 min before alcohol exposure. After 24 h of alcohol exposure, the levels of aspartate transaminase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) in plasma were determined. The degree of hepatic histopathological abnormality was observed by HE staining. The activity of hepatic CAT, hydrogen peroxide (H?O?) level and malondialdehyde (MDA) content in liver tissue were measured by corresponding kits. The levels of tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6) in plasma were determined by ELISA method. The results showed that treatment with ATZ dose-dependently suppressed the elevation of ALT, AST and LDH levels induced by alcohol exposure, and that ATZ alleviated alcohol-induced histopathological alterations. Furthermore, ATZ inhibited the activity of CAT, reduced hepatic levels of H?O?and MDA in alcohol exposed rats. ATZ also decreased the levels of plasma TNF-? and IL-6 in rats with alcohol exposure. These results indicated that ATZ attenuated alcohol-induced acute liver injury in rats, suggesting that CAT might play important pathological roles in the pathogenesis of alcoholic liver injury. PMID:25672632

  12. Alcoholic Hepatitis: Current challenges and future directions

    PubMed Central

    Singal, Ashwani K; Kamath, Patrick S; Gores, Gregory J; Shah, Vijay H

    2013-01-01

    Alcoholic hepatitis is a distinct clinical syndrome amongst people with chronic and active alcohol abuse with a potential for 30–40% mortality at one month amongst those with severe disease. Corticosteroids or pentoxifylline are the current pharmacological treatment options but provide only about 50% survival benefit. These agents are recommended for patients with modified discriminant function (mDF) of ?32 or model for end-stage disease (MELD) score of ?18. The Lille score is used to determine response to steroids. Currently, a minimum of 6 months abstinence from alcohol use is required for patients to receive a liver transplant, a requirement that cannot be met by patients with severe alcoholic hepatitis non-responsive to steroids (Lille score ?0.45). Data are emerging on the benefit of liver transplantation in select patients with first episode of severe alcoholic hepatitis. This review also focuses on recent treatment trials in alcoholic hepatitis including liver transplantation and its associated controversies, as well as possible future targets and pharmacological treatment options for patients with alcoholic hepatitis that are being pursued through upcoming consortium studies. PMID:23811249

  13. 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

  14. 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

  15. Acute Alcohol Consumption, Alcohol Outlets, and Gun Suicide

    PubMed Central

    Branas, Charles C.; Richmond, Therese S.; Ten Have, Thomas R.; Wiebe, Douglas J.

    2014-01-01

    A case–control study of 149 intentionally self-inflicted gun injury cases (including completed gun suicides) and 302 population-based controls was conducted from 2003 to 2006 in a major US city. Two focal independent variables, acute alcohol consumption and alcohol outlet availability, were measured. Conditional logistic regression was adjusted for confounding variables. Gun suicide risk to individuals in areas of high alcohol outlet availability was less than the gun suicide risk they incurred from acute alcohol consumption, especially to excess. This corroborates prior work but also uncovers new information about the relationships between acute alcohol consumption, alcohol outlets, and gun suicide. Study limitations and implications are discussed. PMID:21929327

  16. Acute cytomegalovirus hepatitis in an immunocompetent host.

    PubMed

    Sy, Alexander M; Omobomi, Olabimpe; Lenox, Theodore; Bergasa, Nora V

    2013-01-01

    A 52-year-old woman presented with a 1-week history of recurrent fevers and joint pains accompanied by abdominal and low back discomfort. She has a history of hypoparathyroidism and is on calcium supplements. Physical examination revealed fever and tachycardia. The rest of the examination was normal. Laboratory tests showed newly increased transaminase activity. Serum bilirubin and prothrombin time were normal. She was admitted for evaluation of acute hepatitis. Serology for hepatitis A, B, C and HIV were negative. Her serum acetaminophen and alcohol were undetected. Abdominal imaging was normal. Cultures were sterile. Additional tests for uncommon viral hepatitis included herpes simplex virus, cytomegalovirus and Epstein-Barr virus. Liver biopsy revealed non-specific inflammation. Subsequently, cytomegalovirus serology showed an IgM positive and negative IgG titre. Cytomegalovirus DNA qualitative PCR was also positive. No antiviral medication was given. She continued to have intermittent daily fever but reported no associated symptoms. She was discharged 9 days after admission in stable condition per her request with the advice to follow-up in the clinic in 1 week. Her serum hepatic profile returned to normal and she reported no more episodes of fever. Repeated titres of cytomegalovirus serology showed seroconversion. PMID:24275336

  17. Severe alcoholic hepatitis-current concepts, diagnosis and treatment options

    PubMed Central

    Kim, Won; Kim, Dong Joon

    2014-01-01

    Alcoholic hepatitis (AH) is an acute hepatic manifestation occurring from heavy alcohol ingestion. Alcoholic steatohepatitis (ASH) is histologically characterized by steatosis, inflammation, and fibrosis in the liver. Despite the wide range of severity at presentation, those with severe ASH (Maddrey’s discriminant function ? 32) typically present with fever, jaundice, and abdominal tenderness. Alcohol abstinence is the cornerstone of therapy for AH and, in the milder forms, is sufficient for clinical recovery. Severe ASH may progress to multi-organ failure including acute kidney injury and infection. Thus, infection and renal failure have a major impact on survival and should be closely monitored in patients with severe ASH. Patients with severe ASH have a reported short-term mortality of up to 40%-50%. Severe ASH at risk of early death should be identified by one of the available prognostic scoring systems before considering specific therapies. Corticosteroids are the mainstay of treatment for severe ASH. When corticosteroids are contraindicated, pentoxifylline may be alternatively used. Responsiveness to steroids should be assessed at day 7 and stopping rules based on Lille score should come into action. Strategically, future studies for patients with severe ASH should focus on suppressing inflammation based on cytokine profiles, balancing hepatocellular death and regeneration, limiting activation of the innate immune response, and maintaining gut mucosal integrity. PMID:25349640

  18. Hepatic artery duplex Doppler ultrasound in severe alcoholic hepatitis and correlation with Maddrey’s discriminant function

    PubMed Central

    Abhilash, Haridas; Mukunda, Madhavan; Sunil, Premaletha; Devadas, Krishnadas; Vinayakumar, Katoor Ramakrishnan Nair

    2015-01-01

    Background Alcoholic hepatitis is associated with altered hepatic artery hemodynamics. Maddrey’s discriminant function (MDF) can identify patients with poor prognosis (DF >32). We studied hepatic artery hemodynamic parameters of hepatic artery diameter (HAD), resistive index (RI) and pulsatility index (PI) in severe acute alcoholic hepatitis (SAAH) and for the presence of correlation of parameters with severity factor MDF. Methods A total of 20 consecutive SAAH patients defined as MDF >32 and a group of 20 alcoholic cirrhosis patients without alcoholic hepatitis formed the two study groups. Hepatic artery Doppler parameters HAD, RI, PI were determined after admission in the Gastroenterology Department, Government Medical College, Thiruvananthapuram, India. MDF score of SAAH was calculated at the time of admission to the hospital. Results The mean HAD showed statistically significant increase in SAAH compared with cirrhosis (3.96±0.51 vs. 2.86±0.41, P<0.001). There was statistically significant decrease in mean RI (0.49±0.08 vs. 0.81±0.09, P<0.001) and mean PI (1.67±0.13 vs. 1.80±0.13, P<0.001) in SAAH compared with alcoholic cirrhosis. Statistically significant correlation between MDF and HAD (r=0.63, P<0.003) was found in SAAH. On linear regression, 36% of the variability in MDF could be independently predicted by HAD. Conclusion Hepatic artery parameters of HAD, RI, PI had a significant difference in SAAH compared with alcoholic cirrhosis patients thereby being useful as a diagnostic tool. HAD showed correlation with MDF score assessing the severity of alcoholic hepatitis and may be a useful non-invasive prognostic tool. PMID:25830566

  19. 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

  20. Interleukin-1 production in acute viral hepatitis.

    PubMed Central

    Müller, C; Gödl, I; Ahmad, R; Wolf, H M; Mannhalter, J W; Eibl, M M

    1989-01-01

    The in vitro production of interleukin-1 in 15 children with acute hepatitis A and five children with acute hepatitis B was determined by measuring lymphocyte activating factor secreted by peripheral blood monocytes in a thymocyte proliferation assay. Aluminium hydroxide induced production of lymphocyte activating factor was significantly lower in patients with acute hepatitis A as well as patients with hepatitis B as compared with healthy control subjects. In both forms of acute viral hepatitis production of lymphocyte activating factor was severely depressed during the first week, increased gradually during the further course of the illness, but did not reach normal concentrations within the first three weeks after onset of the acute symptoms of the disease. No correlation could be found between in vitro production of lymphocyte activating factor and the severity of liver disease as estimated by the rise of serum concentrations of transaminases, bilirubin, or several parameters of acute phase reaction (alpha 1 antitrypsin, C reactive protein, erythrocyte sedimentation rate). The reduced production of interleukin-1, as assessed by determination of lymphocyte activating factor, could explain the only moderate acute phase reaction seen during acute viral hepatitis. PMID:2784656

  1. Impaired cerebral autoregulation during acute alcohol withdrawal

    Microsoft Academic Search

    Thomas Jochum; Matthias Reinhard; Michael K. Boettger; Maik Piater; Karl-Jürgen Bär

    2010-01-01

    Heavy alcohol consumption increases the risk for all major types of stroke and is associated with autonomic dysfunction during alcohol withdrawal syndrome (AWS). Cerebral autoregulation is the mechanism by which cerebral perfusion is maintained stable, representing an intrinsic protective system of the cerebral circulation. Here, we aimed to analyze the influence of acute AWS on cerebral hemodynamics in alcohol-dependent patients.We

  2. Recent understanding of immunological aspects in alcoholic hepatitis

    Microsoft Academic Search

    Hidetsugu Saito; Hiromasa Ishii

    2004-01-01

    Alcoholic hepatitis is a rate-limiting step in the development of alcoholic liver disease into liver cirrhosis, and approximately half of the heavy drinkers with alcoholic hepatitis develop liver cirrhosis within 5 years. Immunologic mechanisms may be involved in the individual differences in the clinical course of this disease. Endotoxin from the intestine seems to play an important role in neutrophil

  3. Alcohol abuse and chronic hepatitis C

    Microsoft Academic Search

    Tom Nguyen; M. Mazen Jamal; Timothy R. Morgan

    2007-01-01

    AbstractChronic infection with hepatitis C virus (HCV) and alcohol abuse are two of the most common causes of chronic liver\\u000a disease in the United States. These two entities often coexist and contribute to accelerated development of liver fibrosis,\\u000a cirrhosis, and hepatocellular carcinoma. Although the effect of one drink per day in the setting of chronic HCV infection\\u000a is unclear, there

  4. Is liver biopsy necessary in the management of alcoholic hepatitis?

    PubMed

    Dhanda, Ashwin D; Collins, Peter L; McCune, C Anne

    2013-11-28

    Acute alcoholic hepatitis (AAH) is characterised by deep jaundice in patients with a history of heavy alcohol use, which can progress to liver failure. A clinical diagnosis of AAH can be challenging to make in patients without a clear alcohol history or in the presence of risk factors for other causes of acute liver failure. Other causes of acute on chronic liver failure such as sepsis or variceal haemorrhage should be considered. Liver biopsy remains the only reliable method to make an accurate diagnosis. However, there is controversy surrounding the use of liver biopsy in patients with AAH because of the risks of performing a percutaneous biopsy and limitations in access to transjugular biopsy. We review the existing literature and find there are few studies directly comparing clinical and histological diagnosis of AAH. In the small number of studies that have been conducted the correlation between a clinical and histological diagnosis of AAH is poor. Due to this lack of agreement together with difficulties in accessing transjugular liver biopsy outside tertiary referral centres and research institutions, we cannot advocate universal biopsy for AAH but there remains a definite role for liver biopsy where there is clinical diagnostic doubt or dual pathology. It also adds value in a clinical trial context to ensure a homogeneous trial population and to further our understanding of the disease pathology. Further prospective studies are required to determine whether non-invasive markers can be used to accurately diagnose AAH. PMID:24307775

  5. 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

  6. 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

  7. Toxicology, circumstances and pathology of deaths from acute alcohol toxicity.

    PubMed

    Darke, Shane; Duflou, Johan; Torok, Michelle; Prolov, Tatiana

    2013-11-01

    Alcohol consumption makes a large contribution to premature mortality. In order to extend our understanding of the characteristics, circumstances, toxicology and pathology of alcohol toxicity deaths, all cases presenting to the Department of Forensic Medicine Sydney between 1/1/1997-31/12/2011 with blood alcohol concentrations (BACs) ?0.300 g/100 ml and where the direct cause of death was acute alcohol toxicity were retrieved (n = 83). The mean age was 47.2 yrs and 77.1% were male. The majority (81.9%) of deaths occurred in a home environment, and did not vary across month or day of the week. In 91.6% of cases, a history of alcoholism or heavy alcohol consumption was reported. None were in any form of substance dependence treatment at the time of death. The mean BAC was 0.420 g/100 ml (range 0.300-0.741 g/100 ml). In 33.7% of cases, other substances were detected, predominantly diazepam (28.9%). BACs did not vary significantly by gender, age or BMI. Urine/BAC ratios of >1.25 were seen in 6/43 cases where both samples were available. Cardiac disease was noted in 75.9% of cases and hepatic disease in 91.6%. The only alcohol-related organic brain syndrome pathology identified at autopsy was vermal cerebellar degeneration. PMID:24237834

  8. Extracorporeal liver support in severe alcoholic hepatitis

    PubMed Central

    Parés, Albert; Mas, Antoni

    2014-01-01

    The severity of alcoholic hepatitis (AH) which may coexist with cirrhosis varies greatly, from asymptomatic forms which are detected in alcoholic patients without any sign of liver disease, except laboratory abnormalities, to severe forms characterised by deep jaundice, ascites, hepatic encephalopathy and low prothrombin index. In hospitalized patients the mortality could be as high as 75%. The elevated number of therapeutic proposals reported for more than forty years reveals the lack of efficacy of a particular modality. Even in the most favorable trials, the survival is already very poor and in some cases related to the development of renal failure or hepatorenal syndrome. There are some motivating reports concerning albumin dialysis as a support treatment in patients with severe AH, either alone or in combination with other pharmacological therapies. The favorable effects of albumin dialysis in patients with severe AH suggest that the procedure used alone or in combination with other therapies may have a role in this clinical condition. This will be particularly relevant to offer an alternative therapy in these patients, thus being a potential bridge to recovery or to be listed for liver transplantation. PMID:25009371

  9. Fulminant hepatic failure in pregnant women: acute fatty liver or acute viral hepatitis?

    Microsoft Academic Search

    Saeed S. Hamid; S. M. Wasim Jafri; Haleem Khan; Hasnain Shah; Zaigham Abbas; Howard Fields

    1996-01-01

    Background: Hepatitis E virus, which is endemic in our region, can cause severe liver dysfunction in pregnant women and this can be clinically confused with acute fatty liver of pregnancy.Methods: We studied the clinical and laboratory data as well as the maternal and fetal outcomes of 12 pregnant women presenting with fulminant hepatic failure in order to determine the etiology

  10. Blood culture-positive infections in patients with alcoholic hepatitis.

    PubMed

    Wernlund, Pernille Glahn; Støy, Sidsel; Lemming, Lars; Vilstrup, Hendrik; Sandahl, Thomas Damgaard

    2014-12-01

    Acute alcoholic hepatitis (AH) is a life-threatening disease and its course is often determined by infections. However, the pattern of pathogens has not been studied. We examined the microbiological pathogens that caused blood-borne infection in patients with AH. We included 32 AH patients without infection at inclusion. Patients were followed for 1 month and their infection status was recorded based on clinical records, radiologic exams and cultures of different secreta. Nine patients (28%) developed blood culture-positive infections. The agents were of heterogeneous aetiology and came from various sites of infection. Candida species accounted for three of these infections (33%). Five patients (16%) died, two of which had positive blood cultures. A high fraction was invasively infected by a heterogeneous spectrum of microbes including yeasts and commensal bacteria. This may reflect the severe immune impairment of AH and suggests thorough infection screening and an immediate broad-spectrum antibiotic approach if infection is suspected. PMID:25290580

  11. Theory of Mind Deficits following Acute Alcohol Intoxication

    Microsoft Academic Search

    I. J. Mitchell; S. R. Beck; A. Boyal; V. R. Edwards

    2011-01-01

    Acute alcohol consumption is associated with socially inappropriate behaviour. Such behaviour could in part reflect the potential of alcohol to interfere with social cognition. In this experiment we tested the hypothesis that acute alcohol consumption by regular heavy social drinking young adults would compromise an aspect of social cognition, namely theory of mind (understanding intentions, emotions and beliefs). Participants who

  12. Reduced cardio-respiratory coupling in acute alcohol withdrawal

    Microsoft Academic Search

    Karl-Jürgen Bär; Michael Karl Boettger; Steffen Schulz; Rene Neubauer; Thomas Jochum; Andreas Voss; Vikram K. Yeragani

    2008-01-01

    BackgroundChronic alcoholism represents a risk factor for cardiac arrhythmias. One underlying mechanism is a sympathetically dominated autonomic imbalance. This is especially apparent during acute withdrawal from alcohol. Since linear analysis of heart rate variability may not be entirely adequate to detect such autonomic dysfunction in acute alcohol withdrawal, we applied novel non-linear parameters and measures for cardio-respiratory coupling.

  13. Endothelial dysfunction during acute alcohol withdrawal syndrome

    Microsoft Academic Search

    Thomas Jochum; Markus Weissenfels; Andrea Seeck; Steffen Schulz; Michael K. Boettger; Andreas Voss; Karl-Jürgen Bär

    2011-01-01

    BackgroundEndothelial dysfunction (EF) is a central phenomenon in a variety of conditions associated with increased cardiovascular morbidity. Here, we investigated EF during acute alcohol withdrawal syndrome before and 24h after medication. We aimed to analyze microcirculation, applying the post-occlusive reactive hyperemia (PORH) test and spectral analysis of skin vasomotion as markers of EF. Additionally, we explored whether segmentation of spectral

  14. Acute hepatic failure: limitations of medical treatment and indications for liver transplantation

    Microsoft Academic Search

    M. Peters; K.-H. Meyer zum Büschenfelde; G. Gerken

    1993-01-01

    Acute hepatic failure is defined as hepatic encephalopathy without evidence of previous liver disease. However, at times acute hepatic failure may be the presentation of Wilson's disease, autoimmune chronic active hepatitis, or delta superinfection in patients with chronic active hepatitis B. Currently accepted definitions of acute hepatic failure and of subvarieties thereof have been published [39] based on the time

  15. 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

  16. Change of acute hepatitis B transmission routes in Japan

    Microsoft Academic Search

    Shouko Arima; Kojiro Michitaka; Norio Horiike; Keiko Kawai; Hiroshi Matsubara; Seiji Nakanishi; Masanori Abe; Aki Hasebe; Yoshio Tokumoto; Kazuhisa Yamamoto; Morikazu Onji

    2003-01-01

    Background. Many years have passed since various prophylactic policies for preventing hepatitis B virus (HBV) transmission were begun. We studied the chronological alterations in HBV infectious routes in patients with acute hepatitis B in the past 27 years. Methods. Seventy-two patients with acute HBV infection who were admitted to our hospital during the period 1976 to 2002 were enrolled in

  17. The impact of steatosis and alcohol on hepatitis C

    Microsoft Academic Search

    Sam Galhenage; Manal F. Abdelmalek

    2007-01-01

    Alcohol consumption and hepatic steatosis interact synergistically with hepatitis C virus (HCV) to accelerate fibrosis progression\\u000a and reduce the efficacy of standard antiviral therapies. Research aimed at delineating the viral and host interactions involved\\u000a in the pathogenesis of steatosis in HCV infection may provide novel therapeutic strategies that can modify disease progression\\u000a and improve treatment response. This review discusses the

  18. Profile of Acute Infectious Markers in Sporadic Hepatitis E

    Microsoft Academic Search

    Shoujie Huang; Xuefeng Zhang; Hanmin Jiang; Qiang Yan; Xing Ai; Yijun Wang; Jiaping Cai; Lang Jiang; Ting Wu; Zhongze Wang; Li Guan; J. Wai Kuo Shih; Mun-Hon Ng; Fengcai Zhu; Jun Zhang; Ningshao Xia; Laurent Rénia

    2010-01-01

    Laboratory diagnosis of acute infection of hepatitis E virus (HEV) is commonly based on the detection of HEV RNA, IgM and\\/or rising IgG levels. However, the profile of these markers when the patients present have not been well determined. To clarify the extent of misdiagnosed sporadic hepatitis E in the initial laboratory detection, serial sera of 271 sporadic acute hepatitis

  19. 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

  20. Increased QT interval variability index in acute alcohol withdrawal

    Microsoft Academic Search

    Karl-Jürgen Bär; Michael Karl Boettger; Mandy Koschke; Silke Boettger; Marei Grotelüschen; Andreas Voss; Vikram K. Yeragani

    2007-01-01

    ObjectiveAcute alcohol withdrawal is associated with increased cardiovascular mortality, most likely due to cardiac arrhythmias. As the QT interval reflects the most critical phase for the generation of reentry and thus for arrhythmia, we examined QT variability in patients suffering from acute alcohol withdrawal.

  1. Blood alcohol levels in acute elderly admissions to hospital

    Microsoft Academic Search

    N. D. Penn; O. J. Corrado; L. J. Pitchfork; R. T. Evans; B. H. Mascie-Taylor

    1989-01-01

    Blood alcohol levels were estimated in 141 patients admitted acutely over a one month period to a geriatric unit. Only four (2.8%) had alcohol detectable in their blood. The levels were low, suggesting that alcohol intoxication is not a major factor in the admission of the elderly to hospital.

  2. Hepatic folate metabolism in the chronic alcoholic monkey

    SciTech Connect

    Tamura, T.; Romero, J.J.; Watson, J.E.; Gong, E.J.; Halsted, C.H.

    1981-05-01

    To assess the role of altered hepatic folate metabolism in the pathogenesis of the folate deficiency of chronic alcoholism, the hepatic metabolism of a tracer dose of /sup 3/H-PteGlu was compared in monkeys given 50% of energy as ethanol for 2 years and in control monkeys. Long-term ethanol feeding resulted in mild hepatic injury, with a significant decrease in hepatic folate levels. Chromatographic studies of liver biopsies obtained after the tracer dose indicated that the processes of reduction, methylation, and formylation of reduced folate and the synthesis of polyglutamyl folates were not affected by long-term ethanol feeding. Hepatic tritium levels were significantly decreased in the ethanol-fed group. These studies suggest that the decrease in hepatic folate levels observed after long-term ethanol ingestion is due to a decrease in hepatic folate levels observed after long-term ethanol ingestion is due to a decreased ability to retain folates in the liver, whereas reduction and further metabolism of folates is not affected.

  3. Concomitant endocrine and immune alterations during alcohol intoxication and acute withdrawal in alcohol-dependent subjects.

    PubMed

    Kutscher, Sven; Heise, Dirk J; Banger, Markus; Saller, Berhard; Michel, Martin C; Gastpar, Markus; Schedlowski, Manfred; Exton, Michael

    2002-01-01

    Although both alcohol intoxication and withdrawal have been demonstrated to produce significant endocrine alterations, no data exist on the effects of acute withdrawal on immune functions. Therefore, the current study investigated the effect of alcohol intoxication and acute withdrawal on plasma cortisol, prolactin and catecholamines, and blood leukocyte subset distribution in alcohol-dependent subjects. Nine male alcoholics admitted to the university clinic for alcohol dependence and 9 age-matched controls participated in the study. Blood was drawn from the alcohol-dependent subjects at 10:30 a.m. on day 0 (chronic alcohol intoxication), at the same time during acute alcohol withdrawal (day 1) and following the resolution of acute withdrawal (day 7). Blood was drawn from age- and gender-matched healthy control subjects at the corresponding time points. Plasma was then analyzed for hormone concentrations and blood examined for leukocyte subsets by flow cytometry. Alcohol-dependent patients displayed significantly elevated plasma cortisol during intoxication and withdrawal, which decreased to control levels following resolution of acute withdrawal. Small elevations of plasma prolactin and catecholamines were also observed during intoxication. Furthermore, alcohol-dependent subjects showed reduced absolute numbers of CD4(+) and CD8(+) T cells and natural killer cells compared with healthy controls across all time points. In contrast, although monocyte numbers were lower in alcohol-dependent patients during intoxication, acute alcohol withdrawal increased the number of monocytes in patients. Thus, alcohol dependence produces a general suppression of leukocyte subset populations in blood. However, resolution of acute alcohol withdrawal is associated with a return of plasma cortisol to control levels, and a concomitant increase in peripheral blood monocyte numbers. PMID:11979065

  4. Beware of paracetamol use in alcohol abusers: a potential cause of acute liver injury.

    PubMed

    Manchanda, Achala; Cameron, Christina; Robinson, Geoffrey

    2013-09-27

    There may be under-recognition of acute liver injury following reported therapeutic use of paracetamol in alcoholics. We present the case of an alcoholic patient who developed acute liver injury suspicious for chronic paracetamol toxicity on two occasions. The likely contribution of chronic paracetamol was not recognised at her second presentation, reflecting a need for increased awareness of this potential cause of acute liver injury. The biochemical hallmark of the syndrome is the 'towering' aspartate-aminotransferase (AST), often in the thousands; transaminases above 500 U/L should never be dismissed as secondary to alcoholic liver disease alone. Whether alcoholics are at increased risk of toxicity from therapeutic doses of paracetamol remains controversial, although many cases have been described for over 30 years. Randomised controlled trials to date have failed to show significant hepatic derangement in newly abstinent alcoholics exposed to short courses of paracetamol. We argue that these studies do not reflect the realities of paracetamol use in this population. In addition, alcoholics are at risk of accidental 'staggered overdoses', or repeated supra-therapeutic ingestions. In cases of suspected paracetamol toxicity, administration of the antidote n-acetyl cysteine (NAC) should be considered, even when the patient's serum paracetamol level is normal. PMID:24157994

  5. Reduced baroreflex sensitivity in acute alcohol withdrawal syndrome and in abstained alcoholics

    Microsoft Academic Search

    Karl-Jürgen Bär; Michael Karl Boettger; Silke Boettger; Marei Grotelüschen; Rene Neubauer; Thomas Jochum; Vico Baier; Heinrich Sauer; Andreas Voss

    2006-01-01

    Acute alcohol withdrawal is often associated with increased sympathetic activity, and a decreased baroreflex sensitivity (BRS) can be assumed. Parameters of heart rate variability (HRV), blood pressure variability (BPV), BRS as well as cardiac index (CI), left ventricular work index (LVWI) and total peripheral resistance (TPR) were investigated in 20 patients undergoing acute alcohol withdrawal and matched controls. Measures were

  6. 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

  7. Disturbances in the murine hepatic circadian clock in alcohol-induced hepatic steatosis

    PubMed Central

    Zhou, Peng; Ross, Ruth A.; Pywell, Cameron M.; Liangpunsakul, Suthat; Duffield, Giles E.

    2014-01-01

    To investigate the role of the circadian clock in the development of alcohol-induced fatty liver disease we examined livers of mice chronically alcohol-fed over 4-weeks that resulted in steatosis. Here we show time-of-day specific changes in expression of clock genes and clock-controlled genes, including those associated with lipid and bile acid regulation. Such changes were not observed following a 1-week alcohol treatment with no hepatic lipid accumulation. Real-time bioluminescence reporting of PERIOD2 protein expression suggests that these changes occur independently of the suprachiasmatic nucleus pacemaker. Further, we find profound time-of-day specific changes to the rhythmic synthesis/accumulation of triglycerides, cholesterol and bile acid, and the NAD/NADH ratio, processes that are under clock control. These results highlight not only that the circadian timekeeping system is disturbed in the alcohol-induced hepatic steatosis state, but also that the effects of alcohol upon the clock itself may actually contribute to the development of hepatic steatosis. PMID:24430730

  8. Post-transfusion hepatitis: fatal outcome in two cases with underlying alcoholic liver disease.

    PubMed

    Oyewole, M A; Peura, D A; Johnson, L F

    1985-10-01

    Two patients with underlying alcoholic liver disease who were doing well before receiving multiple blood transfusions for gastrointestinal bleeding died after developing post-transfusion hepatitis (PTH). This hepatitis was associated with an uncharacteristic disparity between transaminase levels. PMID:3877751

  9. Diagnosis and management of acute alcohol withdrawal

    Microsoft Academic Search

    Anne M. Holbrook; Renée Crowther; Chiachen Cheng; Derek King

    ALCOHOL ABUSE PRODUCES A CONSIDERABLE BURDEN OF ILLNESS in the Canadian popu- lation. The diagnosis of alcohol dependence and withdrawal can be difficult, particularly in the setting of covert intake or comorbidity. Two validated scales, the CAGE questionnaire to screen for alcohol abuse and dependence and the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale to assess the severity of

  10. Acute hepatitis B of genotype H resulting in persistent infection

    PubMed Central

    Yamada, Norie; Shigefuku, Ryuta; Sugiyama, Ryuichi; Kobayashi, Minoru; Ikeda, Hiroki; Takahashi, Hideaki; Okuse, Chiaki; Suzuki, Michihiro; Itoh, Fumio; Yotsuyanagi, Hiroshi; Yasuda, Kiyomi; Moriya, Kyoji; Koike, Kazuhiko; Wakita, Takaji; Kato, Takanobu

    2014-01-01

    A 47-year-old man presented with general fatigue and dark urine. The laboratory data showed increased levels of hepatic transaminases. The patient was positive for hepatitis B virus (HBV) markers and negative for anti-human immunodeficiency virus. The HBV-DNA titer was set to 7.7 log copies/mL. The patient was diagnosed with acute hepatitis B. The HBV infection route was obscure. The serum levels of hepatic transaminases decreased to normal ranges without any treatment, but the HBV-DNA status was maintained for at least 26 mo, indicating the presence of persistent infection. We isolated HBV from the acute-phase serum and determined the genome sequence. A phylogenetic analysis revealed that the isolated HBV was genotype H. In this patient, the elevated peak level of HBV-DNA and the risk alleles at human genome single nucleotide polymorphisms s3077 and rs9277535 in the human leukocyte antigen-DP locus were considered to be risk factors for chronic infection. This case suggests that there is a risk of persistent infection by HBV genotype H following acute hepatitis; further cases of HBV genotype H infection must be identified and characterized. Thus, the complete determination of the HBV genotype may be essential during routine clinical care of acute hepatitis B outpatients. PMID:24659896

  11. Occurrence of hepatitis E virus infection in acute hepatitis in Thailand.

    PubMed

    Siripanyaphinyo, U; Boon-Long, J; Louisirirotchanakul, S; Takeda, N; Chanmanee, T; Srimee, B; Namsai, A; Pounsawat, P; Khupulsap, K

    2014-10-01

    Hepatitis E virus (HEV) infection is one of the enterically transmitted types of hepatitis. The present study was undertaken to estimate the occurrence of HEV infection in sporadic acute hepatitis in Thailand. Serum samples were obtained from 614 suspected acute hepatitis patients at two large hospitals in Bangkok during 2008, 2009, and 2011. Acute hepatitis E was identified by the presence of anti-HEV IgM (4.8%) using indirect ELISA kits and/or HEV RNA (4.5%) by a semi-nested reverse transcription-polymerase chain reaction assay. HEV IgM was the most common marker for detection (77%) at diagnosis, either by positive HEV IgM alone or together with HEV RNA, whereas HEV RNA alone was detected in 23% of patients. Overall, 4.2% of cases (26 out of 614) were acute HEV infection with the highest attack rate in the elderly age group. In addition, nucleotide sequence analysis of five HEV samples revealed 92.8-99.8% homology. All viruses were clustered into HEV genotype 3 and were similar genetically to swine HEV strains previously detected in the same area. Therefore, the occurrence of HEV infection with closely related to swine genotype 3 was approximately 4-5% of acute hepatitis cases in Thailand. Anti-HEV IgM was the most common marker at diagnosis. PMID:24984976

  12. [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

  13. Protracted viremia during acute sporadic hepatitis E virus infection

    Microsoft Academic Search

    Santosh Kumar Nanda; Israrul Haque Ansari; Subrat Kumar Acharya; Shahid Jameel; Subrat Kumar Panda

    1995-01-01

    Background\\/Aims: Hepatitis E virus (HEV) is associated with epidemic and sporadic hepatitis in developing countries. The disease is largely self-limited with no long-term sequelae. The source of HEV for maintenance of the disease in an endemic area is unknown. This study investigated the occurrence and duration of viremia in patients with acute sporadic HEV infection. Methods: In 26 of 37

  14. Individual differences in acute alcohol impairment of inhibitory control predict ad libitum alcohol consumption

    PubMed Central

    Weafer, Jessica

    2015-01-01

    Rationale Research has begun to examine how acute cognitive impairment from alcohol could contribute to alcohol abuse. Specifically, alcohol-induced impairment of inhibitory control could compromise the drinker’s ability to stop the self-administration of alcohol, increasing the risk of binge drinking. Objective The present study was designed to test this hypothesis by examining the relation between acute alcohol impairment of inhibitory control and alcohol consumption during a single drinking episode. Materials and methods Twenty-six healthy adults performed a cued go/no-go task that measured inhibitory control. The study tested the degree to which their inhibitory control was impaired by a moderate dose of alcohol (0.65 g/kg) versus a placebo and the extent to which individual differences in this impairment predicted levels of alcohol consumption as assessed by ad lib drinking in the laboratory. Results In accord with the hypothesis, greater impairment of inhibitory control from alcohol was associated with increased ad lib consumption. Conclusion Acute impairment of inhibitory control might be an important cognitive effect that contributes to abuse in addition to the positive rewarding effects of the drug. PMID:18758758

  15. Circadian modulation of acute alcohol sensitivity but not acute tolerance in Drosophila.

    PubMed

    van der Linde, Kim; Lyons, Lisa C

    2011-05-01

    An increased understanding of the factors affecting behavioral and neurological responses to alcohol and alcohol physiology is necessary given the tremendous toll alcohol abuse and alcoholism exert on individuals and society. At the behavioral and molecular levels, the response to alcohol appears remarkably conserved from Drosophila to humans, suggesting that investigations across model species can provide insight into the identification of common modulatory factors. We investigated the interaction between the circadian clock and alcohol sensitivity, alcohol tolerance, and alcohol absorbance in Drosophila melanogaster. Using a loss-of-righting reflex (LoRR) assay, we found that flies exhibit a circadian rhythm in the LoRR, with the greatest sensitivity to alcohol occurring from mid to late night, corresponding to the flies' inactive phase. As predicted, a circadian rhythm in the LoRR was absent in circadian mutant flies and under conditions in which the circadian clock was nonfunctional. Circadian modulation of the response to alcohol was not due to circadian regulation of alcohol absorbance. Similar to other animals, Drosophila develop acute and chronic tolerance to alcohol upon repeat exposures. We found that the circadian clock did not modulate the development of acute alcohol tolerance measured as the difference in sensitivity to alcohol between naïve and pre-exposed flies. Thus, the circadian clock modulates some, but not all, of the behavioral responses to alcohol exposure, suggesting that specific mechanisms underlie the observed circadian modulation of LoRR rather than global cellular circadian regulation. This study provides valuable new insights in our understanding of the circadian modulation of alcohol-induced behaviors that ultimately could facilitate preventative measures in combating alcohol abuse and alcoholism. PMID:21721855

  16. Outcomes after liver transplantation for combined alcohol and hepatitis C virus infection

    PubMed Central

    Khan, Rashid; Singal, Ashwani K; Anand, Bhupinderjit S

    2014-01-01

    Alcohol abuse and chronic hepatitis C virus (HCV) infection are two major causes of chronic liver disease in the United States. About 10%-15% of liver transplants performed in the United States are for patients with cirrhosis due to combined alcohol and HCV infection. Data on outcomes on graft and patient survival, HCV recurrence, and relapse of alcohol use comparing transplants in hepatitis C positive drinkers compared to alcohol abuse or hepatitis C alone are conflicting in the literature. Some studies report a slightly better overall outcome in patients who were transplanted for alcoholic cirrhosis vs those transplanted for HCV alone or for combined HCV and alcohol related cirrhosis. However, some other studies do not support these observations. However, most studies are limited to a retrospective design or small sample size. Larger prospective multicenter studies are needed to better define the outcomes in hepatitis C drinkers. PMID:25232228

  17. 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

  18. Acute Hepatitis C Virus Infection: Diagnosis, Pathogenesis, Treatment

    Microsoft Academic Search

    Florin Alexandru Cãruntu; Loredana Benea

    Diagnosing acute hepatitis C is still difficult. The disease is frequently asymptomatic and there are no specific diagnostic tests. Most frequently, diagnosis is based on anti HCV antibodies serum conversion and, more rarely, on a double serum conversion (initially HCV-RNA undetectable by RT-PCR, subsequently positive and serum conversion for HCV antibodies determined by EIA and RIBA techniques). Evolution of HCV

  19. Hepatitis E as a cause of acute jaundice syndrome in northern Uganda, 2010-2012.

    PubMed

    Gerbi, Gemechu B; Williams, Roxanne; Bakamutumaho, Barnabas; Liu, Stephen; Downing, Robert; Drobeniuc, Jan; Kamili, Saleem; Xu, Fujie; Holmberg, Scott D; Teshale, Eyasu H

    2015-02-01

    Hepatitis E virus (HEV) is a common cause of acute viral hepatitis in developing countries; however, its contribution to acute jaundice syndrome is not well-described. A large outbreak of hepatitis E occurred in northern Uganda from 2007 to 2009. In response to this outbreak, acute jaundice syndrome surveillance was established in 10 district healthcare facilities to determine the proportion of cases attributable to hepatitis E. Of 347 acute jaundice syndrome cases reported, the majority (42%) had hepatitis E followed by hepatitis B (14%), malaria (10%), hepatitis C (5%), and other/unknown (29%). Of hepatitis E cases, 72% occurred in Kaboong district, and 68% of these cases occurred between May and August of 2011. Residence in Kaabong district was independently associated with hepatitis E (adjusted odds ratio = 13; 95% confidence interval = 7-24). The findings from this surveillance show that an outbreak and sporadic transmission of hepatitis E occur in northern Uganda. PMID:25448237

  20. Improving Alcohol Withdrawal Outcomes in Acute Care

    PubMed Central

    Melson, Jo; Kane, Michelle; Mooney, Ruth; McWilliams, James; Horton, Terry

    2014-01-01

    Context Excessive alcohol consumption is the nation’s third leading cause of preventable deaths. If untreated, 6% of alcohol-dependent patients experience alcohol withdrawal, with up to 10% of those experiencing delirium tremens (DT), when they stop drinking. Without routine screening, patients often experience DT without warning. Objective: Reduce the incidence of alcohol withdrawal advancing to DT, restraint use, and transfers to the intensive care unit (ICU) in patients with DT. Design: In October 2009, the alcohol withdrawal team instituted a care management guideline used by all disciplines, which included tools for screening, assessment, and symptom management. Data were obtained from existing datasets for three quarters before and four quarters after implementation. Follow-up data were analyzed and showed a great deal of variability in transfers to the ICU and restraint use. Percentage of patients who developed DT showed a downward trend. Main Outcome Measures: Incidence of alcohol withdrawal advancing to DT and, in patients with DT, restraint use and transfers to the ICU. Results: Initial data revealed a decrease in percentage of patients with alcohol withdrawal who experienced DT (16.4%–12.9%). In patients with DT, restraint use decreased (60.4%–44.4%) and transfers to the ICU decreased (21.6%–15%). Follow-up data indicated a continued downward trend in patients with DT. Changes were not statistically significant. Restraint use and ICU transfers maintained postimplementation levels initially but returned to preimplementation levels by third quarter 2012. Conclusion: Early identification of patients for potential alcohol withdrawal followed by a standardized treatment protocol using symptom-triggered dosing improved alcohol withdrawal management and outcomes. PMID:24867561

  1. Clinical and virological characteristics associated with severe acute hepatitis B.

    PubMed

    Coppola, N; Sagnelli, C; Pisaturo, M; Minichini, C; Messina, V; Alessio, L; Starace, M; Signoriello, G; Gentile, I; Filippini, P; Sagnelli, E

    2014-12-01

    To identify early predictors of a severe or fulminant course in patients with acute viral hepatitis B (AVH-B). One hundred and thirty-eight patients with symptomatic acute hepatitis B observed from 1999 to 2012 were enrolled. For each patient, the demographics, risk factors for the acquisition of hepatitis B virus (HBV) infection, clinical, biochemical and virological data (HBV DNA, HBV DNA sequences) were recorded and analysed. The HBV mutants in the polymerase region were sought in 110 (87%) patients by direct sequencing, and the rtM204V/I mutations also by an allele-specific PCR. AVH-B was severe in 13 (9.4%) of the 138 patients enrolled, fulminant in 6 (4.3%) and with a normal clinical course in 119. The 19 patients with severe or fulminant AVH-B more frequently than the 119 with a normal course stated intravenous drug use (63.2% versus 36.1%, p 0.04) and were HBV-DNA negative (31.6% versus 11.8%, p 0.03) and anti-hepatitis C virus (HCV) positive (57.9% versus 19.3%, p 0.0008); the prevalences of different HBV genotypes and of the rtM204V/I mutant were similar in these three forms of AVH-B. A multivariate logistic regression analysis identified a pre-existing HCV chronic infection as the only factor independently associated with a severe or fulminant clinical course of AVH-B (OR 4.89, 95% CI 1.5-15.94, p 0.01). A pre-existing HCV chronic infection was identified as the only factor independently associated with a severe clinical presentation of acute hepatitis B, an association most probably due to the combination of the liver lesions caused by acute hepatitis B and the pre-existing histological abnormalities related to HCV chronic infection. PMID:24930916

  2. Ecstasy induced acute hepatic failure. Case reports.

    PubMed

    Atayan, Y; Ça??n, Y F; Erdo?an, M A; Harputluoglu, M M M; Bilgic, Y

    2015-01-01

    3,4-methylenedioxymethamphetamine (MDMA), an amphetamine derivative known as ecstasy, has stimulating and hallucinogenic properties. It has become a substance that is widely used especially by young people. Hepatotoxicity is one of the rare side effects of this substance and can be fatal. Ecstasy-induced fulminant hepatitis has been reported in case reports. The clinical course and the prognosis of the cases may differ. In this article, two cases in whom ecstasy-induced fulminant hepatic failure had developed and who were treated with liver transplantation, and one case which recovered with treatment, have been presented. PMID:26118578

  3. Bidirectional interactions between acute psychosocial stress and acute intravenous alcohol in healthy men

    PubMed Central

    Childs, Emma; O'Connor, Sean; de Wit, Harriet

    2011-01-01

    Background The biological mechanisms by which acute stress increases alcohol consumption are unclear. One potential mechanism is that stress acts by altering the pharmacological and subjective effects of alcohol. Acute stress produces a cascade of physiological and psychological effects, each with a distinctive time course. In this study, we investigated whether different phases of response to an acute stress alter the subjective effects of intravenous alcohol, by administering the drug at two different times after the stress. Methods Healthy men (N=25) participated in two sessions; one with the Trier Social Stress Test, the other with a non-stressful control task, each followed by infusions of intravenous alcohol (targeting 40mg% in 5 min) and placebo. One group of participants received alcohol within 1 min of completing the tasks (Alc0, N=11), followed by placebo 30 min later. In the other group (Alc30, N=14), the order of alcohol and placebo infusions was reversed. Subjective effects (i.e., Anxiety, Stimulation, Want more) and physiological measures (heart rate, blood pressure, salivary cortisol) were measured before and at repeated intervals after the tasks and infusions. Results Stress did not change the subjective effects of alcohol in either group. However, when individual differences in alcohol responses were considered, stress differentially altered the stimulant-like and sedative effects of alcohol. Among individuals who exhibited predominantly stimulant responses to alcohol in the non-stressful condition, stress decreased the stimulant-like effects of alcohol and ‘wanting more’. By contrast, among participants who did not report stimulation after alcohol in the control session, stress decreased the sedative effects and increased ‘want more’. In addition, alcohol administered immediately after the TSST dampened cortisol responses yet prolonged negative subjective responses to the stress. Conclusions These findings demonstrate that there are bi-directional relationships between alcohol and stress. Alcohol influences responses to stress, and stress changes reactions to alcohol, depending on an individual's pattern of response to alcohol. This study highlights the fact that stress-alcohol interactions vary among individual drinkers, suggesting that the effects of stress on motivation to drink alcohol may also differ between individuals. PMID:21762177

  4. Efficacy of metadoxine in the management of acute alcohol intoxication.

    PubMed

    Díaz Martínez, M C L R; Díaz Martínez, A; Villamil Salcedo, V; Cruz Fuentes, C

    2002-01-01

    This randomized, open-label study evaluated the efficacy of 300 mg metadoxine (given intravenously) added to standard treatment compared with standard treatment alone in managing the physical and psychological signs of acute alcohol intoxication. Fifty-two acutely intoxicated patients were randomly assigned to one of two groups and followed during a 2-h period. Changes in clinical symptoms, degree of intoxication, and blood alcohol level were monitored. More patients receiving metadoxine in addition to standard therapy significantly improved by at least one degree of intoxication (one clinical category) compared with those receiving standard treatment alone (76.9% versus 42.3%, respectively). Metadoxine-treated patients also exhibited a significantly greater decrease in blood alcohol concentration compared with those receiving standard treatment alone (-105.4 +/- 61.5 mg/dl versus -60.1 +/- 38.6 mg/dl, respectively). Metadoxine improved the clinical signs of acute alcohol intoxication and accelerated alcohol clearance from the blood, thus supporting existing data. In contrast to previous data, these effects were concurrent but independent. No adverse effects were observed with metadoxine therapy. PMID:11921498

  5. The Outcome of Acute Hepatitis C Predicted by the Evolution of the Viral Quasispecies

    Microsoft Academic Search

    Patrizia Farci; Atsushi Shimoda; Alessandra Coiana; Giacomo Diaz; Giovanna Peddis; Jacqueline C. Melpolder; Antonello Strazzera; David Y. Chien; Santiago J. Munoz; Angelo Balestrieri; Robert H. Purcell; Harvey J. Alter

    2000-01-01

    The mechanisms by which hepatitis C virus (HCV) induces chronic infection in the vast majority of infected individuals are unknown. Sequences within the HCV E1 and E2 envelope genes were analyzed during the acute phase of hepatitis C in 12 patients with different clinical outcomes. Acute resolving hepatitis was associated with relative evolutionary stasis of the heterogeneous viral population (quasispecies),

  6. Hepatitis C Virus-Related Acute and Chronic Hepatitis in Hemodialysis Patients

    Microsoft Academic Search

    M. Pluvio; A. Saggese; D. Cirillo; P. Castellino; R. Pempinello; M. D. Iannece; D. Guarnaccia; P. Tassinaro; C. Pluvio; T. Cicchella; C. De Pasquale

    1992-01-01

    The incidence of HCV antibodies has been evaluated in 123 chronic hemodialysis (HD) patients (Group A; 55 M and 68 F) and in 37 consecutive HD patients (group B) admitted to our hospitals for acute hepatitis. In group A, HCV antibodies were present in 27% of the patients. 20 of 36 (55%) had previously received blood transfusions. 21 patients (58%)

  7. An acute psychosocial stressor does not potentiate alcohol cue reactivity in non-treatment-seeking alcoholics

    PubMed Central

    Thomas, Suzanne E.; Randall, Patrick K.; Brady, Kathleen; See, Ronald E.; Drobes, David J.

    2010-01-01

    Background Relapse risk factors, such as psychological stress and alcohol cues, are often encountered together. Understanding how they interact has the potential to improve alcoholism treatments. The present study was conducted to examine whether an acute psychosocial stressor enhanced alcohol cue reactivity in non-treatment-seeking alcoholics. Methods Seventy-nine alcohol dependent individuals (39 women) randomly received either the Trier Social Stress Test or a no-stress control condition. Stress reactivity was measured with serum ACTH and cortisol, mean arterial blood pressure, and subjective distress. Immediately following the stress manipulation, participants held and sniffed a neutral cue then their preferred alcoholic beverage. Cue reactivity was measured by two subjective measures of craving following each cue. Additionally, general craving was assessed with the Alcohol Urge Questionnaire (AUQ) at the beginning and end of the laboratory procedure. Results The stress manipulation showed internal validity on all measures of stress reactivity. There was not a main effect of stress nor a stress x cue interaction on either cue reactivity measure. As expected, there was a main effect of cue (alcohol > neutral cue) on both measures of cue reactivity. General craving increased during the challenge, but not differently by stress group. Magnitude of stress reactivity was not associated with magnitude of cue reactivity, and all results were independent of gender. Conclusion In this well-controlled clinical laboratory study of non-treatment-seeking alcoholics, an acute psychological stressor did not make an alcohol cue a more potent urge-inducing stimulus, and stress had no effect on general alcohol craving. PMID:21143244

  8. CCL20 mediates lipopolysaccharide induced liver injury and is a potential driver of inflammation and fibrosis in alcoholic hepatitis

    PubMed Central

    Affò, Silvia; Morales-Ibanez, Oriol; Rodrigo-Torres, Daniel; Altamirano, José; Blaya, Delia; Dapito, Dianne H; Millán, Cristina; Coll, Mar; Caviglia, Jorge M; Arroyo, Vicente; Caballería, Juan; Schwabe, Robert F; Ginès, Pere; Bataller, Ramón; Sancho-Bru, Pau

    2014-01-01

    Objective Chemokines are known to play an important role in the pathophysiology of alcoholic hepatitis (AH), a form of acute-on-chronic liver injury frequently mediated by gut derived lipopolysaccharide (LPS). In our study, we hypothesise that chemokine CCL20, one of the most upregulated chemokines in patients with AH, is implicated in the pathogenesis of AH by mediating LPS induced liver injury. Design CCL20 gene expression and serum levels and their correlation with disease severity were assessed in patients with AH. Cellular sources of CCL20 and its biological effects were evaluated in vitro and in vivo in chronic, acute and acute-on-chronic experimental models of carbon tetrachloride and LPS induced liver injury. RNA interference technology was used to knockdown CCL20 in vivo. Results CCL20 hepatic and serum levels were increased in patients with AH and correlated with the degree of fibrosis, portal hypertension, endotoxaemia, disease severity scores and short term mortality. Moreover, CCL20 expression was increased in animal models of liver injury and particularly under acute-on-chronic conditions. Macrophages and hepatic stellate cells (HSCs) were identified as the main CCL20 producing cell types. Silencing CCL20 in vivo reduced LPS induced aspartate aminotransferase and lactate dehydrogenase serum levels and hepatic proinflammatory and profibrogenic genes. CCL20 induced proinflammatory and profibrogenic effects in cultured primary HSCs. Conclusions Our results suggest that CCL20 upregulation is strongly associated with LPS and may not only represent a new potential biomarker to predict outcome in patients with AH but also an important mediator linking hepatic inflammation, injury and fibrosis in AH. PMID:24415562

  9. Role of hepatic resident and infiltrating macrophages in liver repair after acute injury.

    PubMed

    You, Qiang; Holt, Michael; Yin, Hao; Li, Guiying; Hu, Cheng-Jun; Ju, Cynthia

    2013-09-15

    Treatment of liver disease, caused by hepatotoxins, viral infections, alcohol ingestion, or autoimmune conditions, remains challenging and costly. The liver has a powerful capacity to repair and regenerate, thus a thorough understanding of this tightly orchestrated process will undoubtedly improve clinical means of restoring liver function after injury. Using a murine model of acute liver injury caused by overdose of acetaminophen (APAP), our studies demonstrated that the combined absence of liver resident macrophages (Kupffer cells, KCs), and infiltrating macrophages (IMs) resulted in a marked delay in liver repair, even though the initiation and extent of peak liver injury was not impacted. This delay was not due to impaired hepatocyte proliferation but rather prolonged vascular leakage, which is caused by APAP-induced liver sinusoidal endothelial cell (LSEC) injury. We also found that KCs and IMs express an array of angiogenic factors and induce LSEC proliferation and migration. Our mechanistic studies suggest that hypoxia-inducible factor (HIF) may be involved in regulating the angiogenic effect of hepatic macrophages (Macs), as we found that APAP challenge resulted in hypoxia and stabilization of HIF in the liver and hepatic Macs. Together, these data indicate an important role for hepatic Macs in liver blood vessel repair, thereby contributing to tissue recovery from acute injury. PMID:23876342

  10. Lamivudine treatment failure in preventing fatal outcome of de novo severe acute hepatitis B in patients with haematological diseases

    Microsoft Academic Search

    Enzo Petrelli; Maria Balducci; Carlo Pieretti; Marco B. Luigi Rocchi; Massimo Clementi; Aldo Manzin

    2001-01-01

    Background: Patients with malignant haematological diseases administered or no longer receiving immunosuppressive therapy are at high risk of reactivation or de novo hepatitis B infection and fulminant hepatitis. Despite promising results in the treatment of chronic hepatitis and its use in selected patients with acute hepatitis B, there is no consensus on lamivudine treatment in severe acute hepatitis portending a

  11. [A case of acute pancreatitis and acute hepatitis caused by ingestion of Ceramium kondoi].

    PubMed

    Kim, Da-bin; Cho, Yoo-Kyung; Song, Hyun Joo; Song, Byung-Cheol

    2013-11-01

    In Korea, the use of herbal remedies is a common cause of drug-induced liver injury. However, the occurrence of both acute pancreatitis and acute hepatitis after taking herbal remedies has rarely been reported. Herein, we report a case of concurrent acute pancreatitis and acute hepatitis associated with Ceramium kondoi ingestion. A 58-year-old woman was diagnosed with advanced gastric cancer 7 months ago. Total gastrectomy and adjuvant chemotherapy was performed without complications. The patient had been well until recently, when she presented with severe abdominal pain after ingestion of Ceramium kondoifor 4 weeks. The laboratory findings demonstrated elevated liver enzymes and lipase, and abdominal computed tomography revealed pancreas swelling with fat infiltration. The diagnosis was made based on the diagnostic criteria for drug induced pancreatitis and the Russel Uclaf Causality Assessment Method scale for drug-induced liver injury. After cessation of Ceramium kondoi, she showed clinical and biochemical improvement. PMID:24262598

  12. Current knowledge and future perspectives on acute hepatitis C infection.

    PubMed

    Hullegie, S J; Arends, J E; Rijnders, B J A; Irving, W L; Salmon, D; Prins, M; Wensing, A M; Klenerman, P; Leblebicioglu, H; Boesecke, C; Rockstroh, J K; Hoepelman, A I M

    2015-08-01

    Acute hepatitis C virus (HCV) infections are frequently seen worldwide in certain risk groups, with an annual incidence rate varying between 0.08% and 66%. Although this incidence is substantial, a delayed diagnosis during chronic infection is most often made in the absence of clinical symptoms in the acute phase of the infection. Currently used methods to diagnose acute HCV infection are IgG antibody seroconversion and repeated HCV RNA measurements, although no definitive diagnostic test is currently available. Progress in the field of adaptive and innate immune responses has aided both advances in the field of HCV vaccine development and a more basic understanding of viral persistence. The rapid changes in the treatment of chronic HCV infection will affect therapeutic regimens for acute HCV infection in the coming years, leading to shorter treatment courses and pegylated interferon-free modalities. This review gives an overview of the current knowledge and uncertainties, together with some future perspectives on acute hepatitis C epidemiology, virology, immunology, and treatment. PMID:25892133

  13. Non Alcoholic Fatty Liver Disease, Hepatic Insulin Resistance and Type 2 Diabetes

    PubMed Central

    Birkenfeld, Andreas L.; Shulman, Gerald I.

    2013-01-01

    Non alcoholic fatty liver disease (NAFLD), hepatic insulin resistance and type 2 diabetes are all strongly associated and are all reaching epidemic proportions. Whether there is a causal link between NAFLD and hepatic insulin resistance is controversial. This review will discuss recent studies in both humans and animal models of NAFLD that have implicated increases in hepatic diacylglycerol content leading to activation of PKC? resulting in decreased insulin signaling in the pathogenesis of NAFLD associated hepatic insulin resistance and type 2 diabetes. The DAG-PKC? hypothesis can explain the occurrence of hepatic insulin resistance observed in most cases of NAFLD associated with obesity, lipodystrophy and type 2 diabetes. PMID:23929732

  14. Acute hepatitis associated with the use of levofloxacin

    Microsoft Academic Search

    João Figueira-Coelho; Olga Pereira; Bárbara Picado; Paula Mendonça; José Neves-Costa; Jorge Neta

    2010-01-01

    Background: Levofloxacin is a fluoroquinolone used globally to treat respiratory, skin, and genitourinary tract infections. It is generally well tolerated and there is a very low risk for liver injury in patients taking this antibiotic.Objective: We report an acute case of hepatitis following treatment with levofloxacin for pneumonia.Case summary: A 77-year-old white male (height, 162 cm; weight, 58 kg) with

  15. Alcoholic hepatitis 2010: A clinician’s guide to diagnosis and therapy

    PubMed Central

    Amini, Maziyar; Runyon, Bruce A

    2010-01-01

    Alcoholic hepatitis (AH) remains a common and life threatening cause of liver failure, especially when it is severe. Although the adjective “acute” is frequently used to describe this form of liver injury, it is usually subacute and has been developing for weeks to months before it becomes clinically apparent. Patients with this form of alcoholic liver disease usually have a history of drinking heavily for many years. While certain aspects of therapy, mainly nutritional support and abstinence are well established, significant debate has surrounded the pharmacologic treatment of AH, and many institutions practice widely varying treatment protocols. In recent years a significant amount of literature has helped focus on the details of treatment, and more data have accumulated regarding risks and benefits of pharmacologic treatment. In particular, the efficacy of pentoxifylline has become increasingly apparent, and when compared with the risks associated with prednisolone, has brought this drug to the forefront of therapy for severe AH. This review will focus on the clinical and laboratory diagnosis and pharmacologic therapies that should be applied during hospitalization and continued into outpatient management. We conclude that the routine use of glucocorticoids for severe AH poses significant risk with equivocal benefit, and that pentoxifylline is a better, safer and cheaper alternative. While the full details of nutritional support lie beyond the scope of this article, nutrition is a cornerstone of therapy and must be addressed in every patient diagnosed with AH. Finally, while traditional psychosocial techniques play a major role in post-hospitalization care of alcoholics, we hope to make the medical clinician realize his or her role in reducing recidivism rates with early and frequent outpatient visits and with the use of baclofen to reduce alcohol craving. PMID:20954276

  16. 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

  17. Hepatitis E virus in patients with acute severe liver injury

    PubMed Central

    Crossan, Claire Louise; Simpson, Kenneth J; Craig, Darren G; Bellamy, Christopher; Davidson, Janice; Dalton, Harry R; Scobie, Linda

    2014-01-01

    AIM: To examine the incidence of hepatitis E (HepE) in individuals with acute liver injury severe enough to warrant treatment at a transplant unit. METHODS: Hepatitis E virus (HEV) is an emerging pathogen in developed countries causing severe illness, particularly in immunocompromised patients or those with underlying chronic liver disease. HepE infection is often under diagnosed, as clinicians can be reluctant to test patients who have not travelled to regions traditionally considered hyperendemic for HepE. There are few data regarding the significance of HEV in patients with very severe acute liver injury in developed countries. Eighty patients with acute severe liver injury attending the Scottish Liver Transplant unit were tested for HEV and anti-HEV IgG and IgM. Severe acute liver injury was defined as a sudden deterioration in liver function confirmed by abnormal liver function tests and coagulopathy or presence of hepatic encephalopathy. Eighty percent of these patients were diagnosed with paracetomol overdose. No patients had a history of chronic or decompensated chronic liver disease at time of sampling. IgG positive samples were quantified against the World Health Organization anti-HEV IgG standard. Samples were screened for HEV viral RNA by quantitative reverse transcription polymerase chain reaction. RESULTS: Four cases of hepatitis E were identified. Three of the four cases were only diagnosed on retrospective testing and were initially erroneously ascribed to drug-induced liver injury and decompensated chronic liver disease, with the cause of the decompensation uncertain. One case was caused by HEV genotype 1 in a traveller returning from Asia, the other three were autochthonous and diagnosed on retrospective testing. In two of these cases (where RNA was detected) HEV was found to be genotype 3, the most prevalent genotype in developed countries. Three patients survived, two of whom had been misdiagnosed as having drug induced liver injury. The fourth patient died from sepsis and liver failure precipitated as a result of hepatitis E infection and previously undiagnosed cirrhosis. Histopathology data to date is limited to mainly that seen for endemic HepE. All patients, with the exception of patient 1, demonstrated characteristics of HepE infection, as seen in previously described locally acquired cases. CONCLUSION: In patients with acute severe liver injury, HEV testing should be part of the initial diagnostic investigation algorithm irrespective of suspected initial diagnosis, age or travel history. PMID:25018853

  18. Molecular Mechanisms for Alcoholic Hepatitis Based on Analysis of Gene Expression Profile

    PubMed Central

    Liu, Minghui; Dou, Yuchang; Sun, Ran; Zhang, Yonggui; Liu, Yansong

    2015-01-01

    Background: Alcoholic hepatitis (AH) is an acute manifestation of alcoholic liver disease with high mortality rates. Objectives: Our aim was to study the molecular mechanisms of AH. Materials and Methods: The differentially expressed genes (DEGs) in liver between AH and control cases were identified by analyzing the GSE28619 microarray data using t-test. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) enrichment analyses were performed using DAVID online tool. The protein-protein interaction (PPI) network was constructed using Search Tool for the Retrieval of Interacting Genes (STRING) and the subnetwork was identified by BioNet. Both PPI network and subnetwork were visualized using the Cytoscape software. Results: Total 908 DEGs (551 up- and 357 down-regulated DEGs) were obtained. The up-regulated DEGs were significantly enriched in 15 pathways and 112 GO biological processes. The down-regulated DEGs were significantly enriched in 22 pathways and 84 GO biological processes. The PPI network with 608 nodes and 2878 interactions was constructed and the subnetwork with 53 nodes and 131 interactions was also identified. The hub DEGs (TSPO, PPIB, NME1 and NME2) were extracted in this subnetwork. Conclusions: TSPO might contribute to the liver damage and AH progression induced by mitochondrial dysfunction through oxidative stress of liver. TSPO interacted with PPIB might play important roles in liver damage in AH. The interaction between NME1 and NME2 might contribute to the transformation from AH to hepatocellular carcinoma.

  19. Review: molecular pathogenesis of hepatic acute porphyrias.

    PubMed

    Grandchamp, B; Puy, H; Lamoril, J; Deybach, J C; Nordmann, Y

    1996-11-01

    The molecular cloning of cDNA and genes encoding enzymes of the haem biosynthetic pathway have permitted the genetic defects underlying acute intermittent porphyria (AIP) and hereditary coproporphyria to be unravelled. In AIP, many different gene abnormalities have been documented since 1989. The prevalence of specific defective alleles among AIP families depends on which human population is studied. Founder effects are likely to account for a high frequency of a single mutation in Finland and, to a lesser extent, in Holland, while many other mutations have only been found once, each of them in a single family. In hereditary coproporphyria several different mutations have already been identified since 1994, suggesting that a large allelic heterogeneity also exists. The search for mutations in variegate porphyria has just started since the recent publication of the human cDNA sequence. Direct detection of the mutations using DNA analysis brings a growing contribution to the detection of asymptomatic carriers among relatives of porphyric patients and will, therefore, improve the prevention of acute attacks. PMID:8985829

  20. Hepatic Steatosis in HIV: A Prospective Study in Patients without Viral Hepatitis, Diabetes, or Alcohol Abuse

    PubMed Central

    Sterling, Richard K; Smith, Paula G.; Brunt, Elizabeth M.

    2012-01-01

    Background and Aims Abnormal liver enzymes (LE) are common in those infected with HIV. Histologic data on those with abnormal LE without viral hepatitis are lacking. Methods HIV positive subjects without HCV, HBV, alcohol abuse, and DM with more than 1 abnormal LE, defined as 1.25 ULN in AST, ALT, or ALP, over 6 months were included. Subjects underwent a 2 hr oral glucose tolerance test, fasting lipids, insulin and glucose for insulin resistance (IR) by HOMA-IR and DEXA for fat distribution. Biopsies were read blindly to clinical data, and scored by Ishak histologic activity index (HAI) for inflammation and fibrosis and NAFLD Activity Score (NAS). Results Fourteen patients underwent biopsy. All were on highly active anti-retroviral therapy (HAART) with undetectable HIV RNA and mean CD4 614. The HAI scores for inflammation and fibrosis were 3.43(1.4) and 1.71(1.26), respectively, and 2 patients had advanced fibrosis (bridging fibrosis/cirrhosis). The majority (65%) of patients had steatosis: grade 1:21%, grade 2:28%, and grade 3:14%. Hepatocyte ballooning was seen in 7 (40%) but NASH was diagnosed only in 4(26%). NAS score of all biopsies of 3.07(2.2; range 0–5). Insulin resistance (HOMA-IR) was higher in those with compared to those without steatosis (3.52 vs. 1.91; p=.11) and highest in those with NASH (4.89). Using multivariate logistic regression, only increased GGT (p=.0009) predicted steatosis while HOMA-IR (p=.0046) predicted NASH. Conclusions Although steatosis is common in HIV patients with abnormal LE without DM, alcohol, or viral hepatitis coinfection, NASH was observed in only 26%. The only clinical or laboratory feature associated with biopsy proven steatosis and NASH were GGT and a calculated measure of insulin resistance, respectively. Further studies are needed in this population to determine the long term clinical significance. PMID:23059409

  1. Viral Superinfection in Previously Unrecognized Chronic Carriers of Hepatitis B Virus with Superimposed Acute Fulminant versus Nonfulminant Hepatitis

    Microsoft Academic Search

    CHIA-MING CHU; CHAU-TING YEH; YUN-FAN LIAW

    1999-01-01

    The role of viral superinfection in hepatitis B surface antigen carriers with superimposed fulminant (n 5 60) versus nonfulminant (n 5 90) acute hepatitis was studied. The frequency of hepatitis A virus (HAV) (0 versus 2.2%), HCV (18.3 versus 21.1%), HDV (15.0 versus 7.8%), and HEV (1.7 versus 4.4%) infection showed no significant difference, while simultaneous HCV and HDV infection

  2. Primary Pancreatic Lymphoma Simulating Acute Cholestatic Hepatitis in a 7-Year-Old Child

    PubMed Central

    Agrawal, Nitesh; Alam, Seema; Rawat, Dinesh; Khanna, Rajeev; Bansal, Kalpana; Bihari, Chhagan

    2015-01-01

    Primary pancreatic lymphoma in children has been described infrequently in literature, and its acute presentation as cholestatic hepatitis is similarly rare. We report a case of a 7-year-old child with primary pancreatic lymphoma presenting as acute infective hepatitis, leading to delay in correct diagnosis and management.

  3. 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

  4. HBs antigen subtypes among acute hepatitis patients in Japan: evidence of imported hepatitis.

    PubMed

    Shiina, S; Fujino, H; Yasuda, H; Kawabe, T; Tagawa, K; Unuma, T; Yoneyama, M; Ohmori, T; Suzuki, S

    1988-07-01

    HBs antigen subtypes were determined among 137 acute hepatitis patients in Japan. The distribution among the 99 male patients was 40 adr, 37 adw, one ayw, and 21 undetermined while that among the 38 female patients was 19 adr, 11 adw, and eight undetermined. The distribution among the male patients was different from that among HBs antigen carriers in Japan, suggesting that they were exposed not only to domestic HBs antigen carriers, but also to other sources. Thirty-one (29 males and two females) of the 137 patients (22.6%) were found to have been abroad at some time during the incubation period. The distribution among them was seven adr, 21 adw, and three undetermined. The majority had the same subtypes that are prevalent in the countries they visited, supporting the hypothesis that most of them had contracted the disease overseas. The remaining 106 patients had a distribution of the subtypes similar to that of domestic HBs antigen carriers. "Imported hepatitis" would be an important cause of acute type B hepatitis in Japan. PMID:3381803

  5. ASMASE IS REQUIRED FOR CHRONIC ALCOHOL INDUCED HEPATIC ENDOPLASMIC RETICULUM STRESS AND MITOCHONDRIAL CHOLESTEROL LOADING

    PubMed Central

    Fernandez, Anna; Matias, Núria; Fucho, Raquel; Ribas, Vicente; Von Montfort, Claudia; Nuño, Natalia; Baulies, Anna; Martinez, Laura; Tarrats, Núria; Mari, Montserrat; Colell, Anna; Morales, Albert; Dubuquoy, Laurent; Mathurin, Philippe; Bataller, Ramón; Caballeria, Joan; Elena, Montserrat; Balsinde, Jesus; Kaplowitz, Neil; Garcia-Ruiz, Carmen; Fernandez-Checa, Jose C.

    2013-01-01

    Background & aims The pathogenesis of alcohol-induced liver disease (ALD) is poorly understood. Here, we examined the role of acid sphingomyelinase (ASMase) in alcohol induced hepatic endoplasmic reticulum (ER) stress, a key mechanism of ALD Methods We examined ER stress, lipogenesis, hyperhomocysteinemia, mitochondrial cholesterol (mChol) trafficking and susceptibility to LPS and concanavalin-A in ASMase?/? mice fed alcohol. Results Alcohol feeding increased SREBP-1c, DGAT-2 and FAS mRNA in ASMase+/+ but not in ASMase?/? mice. Compared to ASMase+/+ mice, ASMase?/? mice exhibited decreased expression of ER stress markers induced by alcohol, but the level of tunicamycin-mediated upregulation of ER stress markers and steatosis was similar in both types of mice. The increase in homocysteine levels induced by alcohol feeding was comparable in both ASMase+/+ mice and ASMase?/? mice. Exogenous ASMase, but not neutral SMase, induced ER stress by perturbing ER Ca2+ homeostasis. Moreover, alcohol-induced mChol loading and StARD1 overexpression were blunted in ASMase?/? mice. Tunicamycin upregulated StARD1 expression and this outcome was abrogated by tauroursodeoxycholic acid. Alcohol-induced liver injury and sensitization to LPS and concanavalin-A were prevented in ASMase?/? mice. These effects were reproduced in alcohol-fed TNFR1/R2?/? mice. Moreover, ASMase does not impair hepatic regeneration following partial hepatectomy. Of relevance, liver samples from patients with alcoholic hepatitis exhibited increased expression of ASMase, StARD1 and ER stress markers. Conclusion Our data indicate that ASMase is critical for alcohol-induced ER stress, and provide a rationale for further clinical investigation in ALD. PMID:23707365

  6. Gene expression profile analysis of rat cerebellum under acute alcohol intoxication.

    PubMed

    Zhang, Yu; Wei, Guangkuan; Wang, Yuehong; Jing, Ling; Zhao, Qingjie

    2015-02-25

    Acute alcohol intoxication, a common disease causing damage to the central nervous system (CNS) has been primarily studied on the aspects of alcohol addiction and chronic alcohol exposure. The understanding of gene expression change in the CNS during acute alcohol intoxication is still lacking. We established a model for acute alcohol intoxication in SD rats by oral gavage. A rat cDNA microarray was used to profile mRNA expression in the cerebella of alcohol-intoxicated rats (experimental group) and saline-treated rats (control group). A total of 251 differentially expressed genes were identified in response to acute alcohol intoxication, in which 208 of them were up-regulated and 43 were down-regulated. Gene ontology (GO) term enrichment analysis and pathway analysis revealed that the genes involved in the biological processes of immune response and endothelial integrity are among the most severely affected in response to acute alcohol intoxication. We discovered five transcription factors whose consensus binding motifs are overrepresented in the promoter region of differentially expressed genes. Additionally, we identified 20 highly connected hub genes by co-expression analysis, and validated the differential expression of these genes by real-time quantitative PCR. By determining novel biological pathways and transcription factors that have functional implication to acute alcohol intoxication, our study substantially contributes to the understanding of the molecular mechanism underlying the pathology of acute alcoholism. PMID:25527120

  7. Moderate Alcohol Consumption Increases Oxidative Stress in Patients With Chronic Hepatitis C

    Microsoft Academic Search

    Cristina Rigamonti; Elisa Mottaran; Emanuela Reale; Roberta Rolla; Valentina Cipriani; Francesca Capelli; Renzo Boldorini; Matteo Vidali; Massimo Sartori; Emanuele Albano

    The mechanisms by which alcohol consumption worsens the evolution of chronic hepatitis C (CHC) are poorly understood. We have investigated the possible interaction between hepatitis C virus (HCV) and ethanol in promoting oxidative stress. Circulating IgG against human serum albumin (HSA) adducted with malondialdehyde (MDA-HSA), 4-hy- droxynonenal (HNE-HSA), or arachidonic acid hydroperoxide (AAHP-HSA) and against oxidized cardiolipin (Ox-CL) were evaluated

  8. Moderate alcohol consumption increases oxidative stress in patients with chronic hepatitis C

    Microsoft Academic Search

    Cristina Rigamonti; Elisa Mottaran; Emanuela Reale; Roberta Rolla; Valentina Cipriani; Francesca Capelli; Renzo Boldorini; Matteo Vidali; Massimo Sartori; Emanuele Albano

    2003-01-01

    The mechanisms by which alcohol consumption worsens the evolution of chronic hepatitis C (CHC) are poorly understood. We have investigated the possible interaction between hepatitis C virus (HCV) and ethanol in promoting oxidative stress. Circulating IgG against human serum albumin (HSA) adducted with malondialdehyde (MDA-HSA), 4-hydroxynonenal (HNE-HSA), or arachidonic acid hydroperoxide (AAHP-HSA) and against oxidized cardiolipin (Ox-CL) were evaluated as

  9. Hepatitis C Plus Alcohol or Marijuana: Which Is Worse?

    Microsoft Academic Search

    Ayman A. Koteish

    2010-01-01

    Despite advances in hepatitis C therapy and better knowledge of viral\\/host factors related to disease progression, the hepatitis\\u000a C virus remains the leading cause of chronic liver disease, causing progression to end-stage liver disease (ESLD) as well\\u000a as the development of hepatocellular carcinoma. Because hepatitis C virus acquisition is linked to an addictive behavior (ie,\\u000a injection drug use), any perceived

  10. Acute effects of propylthiouracil on hemodynamics and oxygen content in patients with alcoholic cirrhosis

    Microsoft Academic Search

    Philippe Sogni; Antoine Hadengue; Richard Moreau; Olivier Le Moine; Thierry Soupison; Frédérique Oberti; Robert Farinotti; Didier Lebrec

    1997-01-01

    Background\\/Aims: The antithyroid drug porpylthio-uracil has been suggested for the treatment of alcoholic liver disease. Its beneficial effects could be due to either a decrease in hepatic oxygen consumption or an increase in hepatic blood flow. The aim of this study was to test these two hypotheses in patients with proven alcoholic cirrhosis.Methods: The pharmacokinetic parameters after intravenous administration of

  11. CD36-deficient mice are resistant to alcohol- and high-carbohydrate-induced hepatic steatosis[S

    PubMed Central

    Clugston, Robin D.; Yuen, Jason J.; Hu, Yunying; Abumrad, Nada A.; Berk, Paul D.; Goldberg, Ira J.; Blaner, William S.; Huang, Li-Shin

    2014-01-01

    CD36 is a scavenger receptor with multiple ligands and cellular functions, including facilitating cellular uptake of free fatty acids (FFAs). Chronic alcohol consumption increases hepatic CD36 expression, leading to the hypothesis that this promotes uptake of circulating FFAs, which then serve as a substrate for triglyceride (TG) synthesis and the development of alcoholic steatosis. We investigated this hypothesis in alcohol-fed wild-type and Cd36-deficient (Cd36?/?) mice using low-fat/high-carbohydrate Lieber-DeCarli liquid diets, positing that Cd36?/? mice would be resistant to alcoholic steatosis. Our data show that the livers of Cd36?/? mice are resistant to the lipogenic effect of consuming high-carbohydrate liquid diets. These mice also do not further develop alcoholic steatosis when chronically fed alcohol. Surprisingly, we did not detect an effect of alcohol or CD36 deficiency on hepatic FFA uptake; however, the lower baseline levels of hepatic TG in Cd36?/? mice fed a liquid diet were associated with decreased expression of genes in the de novo lipogenesis pathway and a lower rate of hepatic de novo lipogenesis. In conclusion, Cd36?/? mice are resistant to hepatic steatosis when fed a high-carbohydrate liquid diet, and they are also resistant to alcoholic steatosis. These studies highlight an important role for CD36 in hepatic lipid homeostasis that is not associated with hepatic fatty acid uptake. PMID:24280415

  12. Acute hepatitis and myositis associated with Erythema infectiosum by Parvovirus B19 in an adolescent

    PubMed Central

    2014-01-01

    Background Erythema infectiosum is the most common clinical manifestation of Parvovirus B19 infection although it has also been associated with rheumatologic diseases and various types of systemic vasculitides. Acute hepatitis and benign myositis however are rarely reported in association with Parvovirus B19 infection. Case presentation Here we report a 14-year old male, who developed acute hepatitis and benign myositis associated with erythema infectiosum following Parvovirus B19 infection. Conclusion Parvovirus B19 infection has rarely been associated with acute hepatitis and exceptionally rarely with benign myositis. Parvovirus B19 should be considered in the differential diagnosis of acute non-A to E hepatitis and in the case of acute benign myositis presenting with a rash especially in children. PMID:24410941

  13. Similar morphological and intracellular biochemical changes in alcoholic acute pancreatitis and ischemic acute pancreatitis in rats.

    PubMed

    Siech, M; Weber, H; Letko, G; Dummler, W; Schoenberg, M H; Beger, H G

    1997-01-01

    Pancreatic hyperstimulation with simultaneous duct obstruction does not cause the typical features of acute pancreatitis, therefore the role of an additional challenge, such as either ethanol intoxication or short-term ischemia, was studied. Alcoholic pancreatitis was induced in 28 rats by acute ethanol intoxication (0.25 LD50) and an obstruction/hyperstimulation mechanism (clip of the biliopancreatic duct for 20 min and intravenous stimulation with 5 U of cholecystokinin and secretin each). Ischemic pancreatitis was performed by obstruction/hyperstimulation and subsequent pancreatic ischemia by clamping the supplying arteries for 40 min. The macro- and microscopic alterations were evaluated and graded by a scoring system. Additionally, the pancreas was removed in 50% of the animals and the pancreatic acini were prepared. From those acini the intracellular enzymes trypsinogen, kallikreinogen, amylase, lipase, glucuronidase, and acidic phosphatases were determined. While obstruction/hyperstimulation, 40 min of ischemia, or ethanol alone did not induce acute pancreatitis, a combination of obstruction/hyperstimulation with either ethanol or ischemia resulted in acute pancreatitis in 68 and 60% of treated rats, respectively. Similarly, both models were characterized by extrapancreatic fat necrosis and acinar necrosis at the periphery of the lobules. Almost all intracellular enzymes were elevated in both pancreatitis models compared to sham-operated controls. Both alcohol and ischemia were insults that sensitize the pancreas to develop acute pancreatitis after obstruction/hyperstimulation. Since the observed morphologic and enzymatic alterations in both models are very similar, alcohol and ischemia might have some common pathways by which they make the pancreas vulnerable to enzymatic attacks. PMID:8981505

  14. Chronic Alcohol Intake Upregulates Hepatic Expression of Carotenoid Cleavage Enzymes and PPAR in Rats12

    PubMed Central

    Luvizotto, Renata A. M.; Nascimento, André F.; Veeramachaneni, Sudipta; Liu, Chun; Wang, Xiang?Dong

    2010-01-01

    Excessive and chronic alcohol intake leads to a lower hepatic vitamin A status by interfering with vitamin A metabolism. Dietary provitamin A carotenoids can be converted into vitamin A mainly by carotenoid 15,15’-monooxygenase 1 (CMO1) and, to a lesser degree, carotenoid 9?10’-monooxygenase 2 (CMO2). CMO1 has been shown to be regulated by several transcription factors, such as the PPAR, retinoid X receptor, and thyroid receptor (TR). The regulation of CMO2 has yet to be identified. The impact of chronic alcohol intake on hepatic expressions of CMO1 and CMO2 and their related transcription factors are unknown. In this study, Fischer 344 rats were pair-fed either a liquid ethanol Lieber-DeCarli diet (n = 10) or a control diet (n = 10) for 11 wk. Hepatic retinoid concentration and expressions of CMO1, CMO2, PPAR?, PPAR?, and TR? as well as plasma thyroid hormones levels were analyzed. We observed that administering alcohol decreased hepatic retinoid levels but increased mRNA concentrations of CMO1, CMO2, PPAR?, PPAR?, and TR? and upregulated protein levels of CMO2, PPAR?, and PPAR?. There was a positive correlation of PPAR? with CMO1 (r = 0.89; P < 0.0001) and both PPAR? and PPAR? with CMO2 (r = 0.72, P < 0.001 and r = 0.62, P < 0.01, respectively). Plasma thyroid hormone concentrations did not differ between the control rats and alcohol-fed rats. This study suggests that chronic alcohol intake significantly upregulates hepatic expression of CMO1 and, to a much lesser extent, CMO2. This process may be due to alcohol-induced PPAR? expression and lower vitamin A status in the liver. PMID:20702748

  15. Molecular Mechanisms of Hepatic Fibrosis in Non-Alcoholic Steatohepatitis

    Microsoft Academic Search

    Krista Rombouts; Fabio Marra

    2010-01-01

    Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease in Western countries. The more severe form of this condition, non-alcoholic steatohepatitis (NASH), may progress to cirrhosis and its complications. Fibrosis and cirrhosis are the final outcomes of all chronic liver diseases; however, some morphological and biological differences distinguish fibrosis due to NASH from the forms secondary to

  16. Acute liver failure caused by severe acute hepatitis B: a case series from a multi-center investigation

    PubMed Central

    2014-01-01

    Background Few data can be available regarding acute liver failure (ALF) caused by severe acute hepatitis B up to now. This study aims to report such cases from China. Findings We conducted a multi-center investigation on ALF from 7 tertiary hospitals in different areas of China. A total of 11 patients with ALF caused by severe acute hepatitis B were finally identified. In these patients, there were 10 male and 1 female patients. As a serious complication, apparent hemorrhage occurred in 9 patients. Eventually, in these 11 patients, 4 survived and 7 died. 4 died of heavy bleeding, 2 died of systemic inflammatory response syndrome and 1 died of irreversible coma. No patients received liver transplantation. Conclusions ALF caused by severe acute hepatitis B is worthy of formal studies based on its rarity and severity. PMID:24958233

  17. Cardiorenal syndrome followed by acute hepatitis C in a patient with acute myeloid leukemia

    PubMed Central

    Mihaila, Romeo-Gabriel

    2014-01-01

    Cardiorenal syndrome involves altering cardiac and renal function. These patients frequently develop resistance to diuretic therapy, so that ultrafiltration should be applied in emergency for saving them. Concomitant presence of an active hematologic malignancy represents an important complicating factor. We present the case of an elderly patient with acute myeloid leukemia, appeared on the background of myelodysplastic syndrome who, during marrow aplasia occurred after the first course of induction chemotherapy, developed a cardiorenal syndrome, which required repeated sessions of hemodialysis. Complete hematologic remission and efficiency of fluid depletion therapy allowed the second course of polychemotherapy, after which the patient developed an acute hepatitis C. After 8 months of complete hematologic remission that persists, the patient will be put on the standard antivirusologic treatment. PMID:24949003

  18. High-dose interferon-? 2b treatment prevents chronicity in acute hepatitis C

    Microsoft Academic Search

    Wolfgang Vogel; Ivo Graziadei; Florian Umlauft; Christian Datz; Franz Hackl; Stefan Allinger; Kurt Grünewald; Josef Patsch

    1996-01-01

    Acute hepatitis C takes a chronic course in 50–80% of cases. Results with interferon treatment are conflicting. To evaluate the efficacy of high-dose interferon treatment, we initiated a pilot study in 1992 using 10 MU interferon-?2b administered subcutaneously daily until normalization of serum transaminase concentrations. Treatment was begun when a diagnosis of acute hepatitis C was established. HCV-RNA was tested

  19. Liver transplantation for acute liver failure related to autochthonous genotype 3 hepatitis E virus infection.

    PubMed

    Aherfi, Sarah; Borentain, Patrick; Raissouni, Ferdaous; Le Goffic, Aude; Guisset, Michel; Renou, Christophe; Grimaud, Jean-Charles; Hardwigsen, Jean; Garcia, Stéphane; Botta-Fridlund, Danielle; Nafati, Cyril; Motte, Anne; Le Treut, Yves Patrice; Colson, Philippe; Gerolami, René

    2014-02-01

    Hepatitis E virus of genotype 3 (HEV-3) is an emerging cause of sporadic autochthonous acute hepatitis in Europe. Although spontaneous outcome of hepatitis E is usually favorable, fulminant liver failure has been described worldwide. In Europe, autochthonous hepatitis E associated with fulminant hepatic failure and leading to liver transplantation has been exceptionally reported. We report here four cases of fulminant and sub-fulminant hepatitis E proposed for liver transplantation in Marseille University hospitals between July 2006 and March 2010. HEV diagnosis relied on detection of anti-HEV IgM antibodies and HEV RNA in serum samples. All cases were men, with no travel history in hyperendemic areas. HEV sequence analyses revealed genotype 3 HEV in the four patients. Liver histology indicated severe acute hepatitis in all of them, pre-existing fibrosis being found in two cases. Two patients underwent liver transplantation, and the two other patients could not be transplanted due to septic complications and died. HEV testing should be performed for the initial evaluation of every acute liver failure regardless of the epidemiological and clinical context. With respect to the potentially fulminant evolution of HEV genotype 3 infections, treatment with ribavirin of severe acute hepatitis E should be considered. PMID:24462173

  20. Alcohol Consumption in Patients with Acute or Chronic Pancreatitis

    Microsoft Academic Search

    J. Sand; P. G. Lankisch; I. Nordback

    2007-01-01

    Understanding of the relation between the alcoholic consumption and the development of pancreatitis should help in defining the alcoholic etiology of pancreatitis. Although the association between alcohol consumption and pancreatitis has been recognized for over 100 years, it remains still unclear why some alcoholics develop pancreatitis and some do not. Surprisingly little data are available about alcohol amounts, drinking patterns,

  1. Acute hepatitis due to hepatitis A virus subgenotype IA as an imported infectious disease from Indonesia.

    PubMed

    Utsumi, Takako; Yano, Yoshihiko; Amin, Mochamad; Lusida, Maria I; Soetjipto; Hotta, Hak; Hayashi, Yoshitake

    2014-01-01

    A 25-year-old Japanese man was admitted with general malaise and fever, which had developed 12 days after coming back to Japan from Indonesia. Blood examination revealed elevated transaminase levels and positivity for the IgM anti-HAV antibody; therefore, he was diagnosed with acute hepatitis A. HAV-RNA was detected in his serum and phylogenetically classified as subgenotype IA. The partial genome in the VP1/P2A region was consistent with the strain recently isolated from Surabaya, which indicated that he had been infected during his stay in Indonesia. Thus, HAV vaccination is recommended before visiting HAV-endemic countries for a long period of time. PMID:25339259

  2. [Acute pancreatitis and acalculous cholecystitis associated with viral hepatitis A].

    PubMed

    Arcana, Ronald; Frisancho, Oscar

    2011-01-01

    We report the case of a 14 year-old male from Lima. He is a student with a history of bronchial asthma since age 4 receives conditional salbutamol, corticosteroids used for asthma attacks (a crisis in 2010, 1 month ago) Refuses surgery or transfusions. He presented with a two weeks for abdominal pain, nausea, fever, and jaundice. Epigastric pain is colicky and radiated back to righ upper quadrant, refers in addition to nausea and fever, for ten days notice jaundice of skin and sclera. On examen he was lucid, with jaundice of skin and mucous membranes. There was no palpable lymph nodes, abdomen with bowel sounds, soft, depressible, liver span of 15cm, positive Murphy, no peritonitis. The laboratory findings showed hemoglobin 13gr, MCV 90, platelets 461.000/mm3, WBC 4320/mm, lymphocytes 1700 (39%). total bilirubin: 8.8, B Direct: 7.6, ALT (alanine aminotransferase): 3016, AST (aspartate aminotransferase): 984, alkaline phosphatase: 250, albumin: 3.34gr%, globulin: 2.8, amylase: 589 (high serum amylase), TP: 17, INR: 1.6, VHA IgM positive. 89 mg glucose, urea 19 mg%, creatinine 0.5 mg Hemoglobin 13gr, MCV 90 Platelet 461000/mm3, WBC 4320/mm, Lymphocytes 1700 (39%). The nuclear magnetic resonance showed hepatomegaly associated with thickening of gallbladder wall without stones up to 11mm inside. No bile duct dilatation, bile duct 4mm, pancreas increased prevalence of body size. Mild splenomegaly and free fluid in the space of Morrison and right flank. Abdominal ultrasound revealed a gallbladder wall thickness (11mm), without stones in his light. Pancreas to increase volume with peripancreatic fluid free perivesicular with a volume of 430 cc. Findings consistent with acute acalculous cholecystitis and acute pancreatitis. CT-scan showed enlarged pancreas with predominance of body and tail with peripancreatic edema; the gallbladder was thickening. We report this case because the extrahepatic manifestations of viral hepatitis A infection are uncommon, specially the associated with acute acalculous cholecystitis and acute pancreatitis simultaneous. PMID:21836659

  3. Chronic and acute alcohol administration induced neurochemical changes in the brain: Comparison of distinct zebrafish populations

    PubMed Central

    Chatterjee, Diptendu; Shams, Soaleha; Gerlai, Robert

    2014-01-01

    The zebrafish is increasingly utilized in the analysis of the effects of ethanol (alcohol) on brain function and behaviour. We have shown significant population dependent alcohol induced changes in zebrafish behaviour and have started to analyze alterations in dopaminergic and serotoninergic responses. Here, we analyze the effects of alcohol on levels of selected neurochemicals using a 2×3 (chronic x acute) between subject alcohol exposure paradigm randomized for two zebrafish populations, AB and SF. Each fish first received the particular chronic treatment (0 or 0.5 vol/vol% alcohol) and subsequently the acute exposure (0, 0.5 or 1.0% alcohol). We report changes in levels of dopamine, DOPAC, serotonin, 5HIAA, glutamate, GABA, aspartate, glycine and taurine as quantified from whole brain extracts using HPLC. We also analyze Mono-Amine Oxidase (MAO) and Tyrosine Hydroxylase (TH) enzymatic activity. The results demonstrate that compared to SF, AB is more responsive to both acute alcohol exposure and acute alcohol withdrawal at the level of neurochemistry, a finding that correlates well with prior behavioural observations and one which suggests the involvement of genes in the observed alcohol effects. We discuss correlations between the current results and prior behavioural findings, and stress the importance of characterization of zebrafish strains for future behaviour genetic and psychopharmacology studies. PMID:24381007

  4. A male patient with severe acute hepatitis who was domestically infected with a genotype H hepatitis B virus in Iwate, Japan

    Microsoft Academic Search

    Ichiro Kumagai; Koichi Abe; Takayoshi Oikawa; Akihiro Sato; Shinichiro Sato; Ryujin Endo; Yasuhiro Takikawa; Kazuyuki Suzuki; Tomoyuki Masuda; Shigehiko Sainokami; Kazunori Endo; Masaharu Takahashi; Hiroaki Okamoto

    2007-01-01

    Although all eight genotypes of hepatitis B virus (HBV) strains are circulating in Japan, no cases of acute hepatitis with\\u000a foreign HBV strains of genotype H have thus far been reported in Japan. Here, we report a 35-year-old Japanese patient with\\u000a severe acute hepatitis who was domestically infected with genotype H HBV. On admission, he had a high HBV load

  5. Hepatic Free Cholesterol Accumulates in Obese, Diabetic Mice and Causes Non-Alcoholic Steatohepatitis

    PubMed Central

    Van Rooyen, Derrick M; Larter, Claire Z; Haigh, W Geoffrey; Yeh, Matthew M; Ioannou, George; Kuver, Rahul; Lee, Sum P; Teoh, Narci C; Farrell, Geoffrey C

    2011-01-01

    Background & Aims Type-2 diabetes and non-alcoholic steatohepatitis (NASH) are associated with insulin resistance and disordered cholesterol homeostasis. We investigated the basis for hepatic cholesterol accumulation with insulin resistance and its relevance to pathogenesis of NASH. Methods Alms1 mutant (foz/foz) and wild-type (WT) NOD.B10 mice were fed high-fat diets that contained varying percentages of cholesterol; hepatic lipid pools and pathways of cholesterol turnover were determined. Hepatocytes were exposed to insulin concentrations that circulate in diabetic foz/foz mice. Results Hepatic cholesterol accumulation was attributed to up-regulation of low density lipoprotein receptor (LDLR) via activation of sterol regulatory element binding protein-2 (SREBP-2), reduced biotransformation to bile acids, and suppression of canalicular pathways for cholesterol and bile acid excretion in bile. Exposing primary hepatocytes to concentrations of insulin that circulate in diabetic Alms1 mice replicated the increases in SREBP-2 and LDLR and suppression of bile salt export pump. Removing cholesterol from diet prevented hepatic accumulation of free cholesterol and NASH; increasing dietary cholesterol exacerbated hepatic accumulation of free cholesterol, hepatocyte injury or apoptosis, macrophage recruitment, and liver fibrosis. Conclusions In obese, diabetic mice, hyperinsulinemia alters nuclear transcriptional regulators of cholesterol homeostasis, leading to hepatic accumulation of free cholesterol; the resulting cytotoxicity mediates transition of steatosis to NASH. PMID:21703998

  6. Predictors of Alcohol Use Among Rural Drug Users After Disclosure of Hepatitis C Virus Status

    PubMed Central

    Stephens, Dustin B.; Havens, Jennifer R.

    2013-01-01

    Objective: Alcohol consumption dramatically increases the risk of liver damage among those with hepatitis C virus (HCV) infection, yet the impact of HCV status disclosure and standard informational counseling on alcohol use among rural drug users remains poorly understood. Method: In this prospective study, 503 rural Appalachian drug users were recruited using respondent-driven sampling. Participants were tested for HCV antibodies, and data on sociodemographic characteristics, lifetime and past-30-day drug and alcohol use, and psychiatric disorders were collected by interviewer-administered questionnaires. A total of 470 participants returned after 6 months for follow-up; however,4 of those had no history of alcohol use, thus leaving a final sample size of 466. Multivariate negative binomial regression was used to determine the effect of disclosure of HCV status and posttest counseling on alcohol consumption at follow-up. Results: Despite an overall decrease in drinking frequency in the cohort, those who were HCV-positive were drinking at a frequency similar to their HCV-negative counterparts at follow-up, despite posttest counseling informing them of the risks of alcohol use with an HCV diagnosis (adjusted incidence rate ratio = 1.07, 95% CI [0.72, 1.61]). Significant predictors of increased days of alcohol use after 6 months included baseline alcohol use, baseline marijuana use, and meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for antisocial personality disorder. Those using OxyContin at baseline had significantly fewer days of alcohol use at follow-up. Conclusions: HCV status disclosure and standard informational counseling alone do not curtail drinking among HCV-positive drug users in the rural setting. Targeted interventions with regard to alcohol use are warranted in order to mitigate the damage of the HCV epidemic. PMID:23490567

  7. A case of acute motor and sensory axonal neuropathy following hepatitis a infection.

    PubMed

    Jo, Yoon-Sik; Han, Sang-Don; Choi, Jin-Yong; Kim, Ick Hee; Kim, Yong-Duk; Na, Sang-Jun

    2013-12-01

    Acute motor and sensory axonal neuropathy (AMSAN) are recently described subtypes of Guillain-Barre syndrome characterized by acute onset of distal weakness, loss of deep tendon reflexes, and sensory symptoms. A 21-yr-old male was transferred to our hospital due to respiration difficulties and progressive weakness. In laboratory findings, immunoglobulin M antibodies against hepatitis A were detected in blood and cerebrospinal fluid. The findings of motor nerve conduction studies showed markedly reduced amplitudes of compound muscle action potentials in bilateral peroneal, and posterior tibial nerves, without evidence of demyelination. Based on clinical features, laboratory findings, and electrophysiologic investigation, the patient was diagnosed the AMSAN following acute hepatitis A viral infection. The patient was treated with intravenous immunoglobulin and recovered slowly. Clinicians should consider this rare but a serious case of AMSAN following acute hepatitis A infection. PMID:24339719

  8. A Case of Acute Motor and Sensory Axonal Neuropathy Following Hepatitis A Infection

    PubMed Central

    Jo, Yoon-Sik; Han, Sang-Don; Choi, Jin-Yong; Kim, Ick Hee; Kim, Yong-Duk

    2013-01-01

    Acute motor and sensory axonal neuropathy (AMSAN) are recently described subtypes of Guillain-Barre syndrome characterized by acute onset of distal weakness, loss of deep tendon reflexes, and sensory symptoms. A 21-yr-old male was transferred to our hospital due to respiration difficulties and progressive weakness. In laboratory findings, immunoglobulin M antibodies against hepatitis A were detected in blood and cerebrospinal fluid. The findings of motor nerve conduction studies showed markedly reduced amplitudes of compound muscle action potentials in bilateral peroneal, and posterior tibial nerves, without evidence of demyelination. Based on clinical features, laboratory findings, and electrophysiologic investigation, the patient was diagnosed the AMSAN following acute hepatitis A viral infection. The patient was treated with intravenous immunoglobulin and recovered slowly. Clinicians should consider this rare but a serious case of AMSAN following acute hepatitis A infection. PMID:24339719

  9. Nicotinamide Counteracts Alcohol-Induced Impairment of Hepatic Protein Metabolism in Humans1,2

    Microsoft Academic Search

    Elena Volpi; Paola Lucidi; Guido Cruciani; Francesca Monacchia; Gianpaolo Reboldi; Paolo Brunetti; Geremia B. Bolli; Pierpaolo De Feo

    We have recently shown that a large amount of wine (750 mL, Ç70 g of alcohol) markedly impairs postprandial hepatic protein metabolism in healthy subjects. This is probably due to the shift in the intracellular redox state (increased NADH\\/NAD\\/) induced by ethanol oxidation. If this hypothesis is true, the administration of nicotinamide (NAD\\/ precursor) should provide NAD\\/ in excess and

  10. 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.

  11. Patterns of Alcohol Consumption and Acute Myocardial Infarction: A Case-Crossover Analysis

    Microsoft Academic Search

    M. G. Gerlich; A. Krämer; G. Gmel; M. Maggiorini; T. F. Lüscher; H. Rickli; G. R. Kleger; J. Rehm

    2009-01-01

    Background: Alcohol consumption has been causally related to the incidence of coronary heart disease, but the role of alcohol before the event has not been explored in depth. This study tested the hypothesis that heavy drinking (binge drinking) increases the risk of subsequent acute myocardial infarctions (AMI), whereas light to moderate drinking occasions decrease the risk. Methods: Case-crossover design of

  12. The effects of acute alcohol consumption on recovery from a simulated rugby match

    Microsoft Academic Search

    Matthew J. Barnes; Toby Mundel; Stephen R. Stannard

    2012-01-01

    In this study, we investigated the effects of acute post-exercise alcohol consumption on measures of physical performance, creatine kinase, and immunoendocrine function in the 48 h following a rugby game simulation. Ten male senior rugby union players completed a rugby game simulation after which they consumed either 1 g of alcohol per kilogram of body mass or a non-alcoholic control beverage. Agility,

  13. The effects of acute alcohol consumption on recovery from a simulated rugby match

    Microsoft Academic Search

    Matthew J. Barnes; Toby Mundel; Stephen R. Stannard

    2011-01-01

    In this study, we investigated the effects of acute post-exercise alcohol consumption on measures of physical performance, creatine kinase, and immunoendocrine function in the 48 h following a rugby game simulation. Ten male senior rugby union players completed a rugby game simulation after which they consumed either 1 g of alcohol per kilogram of body mass or a non-alcoholic control beverage. Agility,

  14. The incidence of acute pancreatitis: impact of social deprivation, alcohol consumption, seasonal and demographic factors1

    PubMed Central

    Roberts, SE; Akbari, A; Thorne, K; Atkinson, M; Evans, PA

    2013-01-01

    Background The incidence of acute pancreatitis has increased sharply in many European countries and the USA in recent years. Aim To establish trends in incidence and mortality for acute pancreatitis in Wales, UK, and to assess how incidence may be linked to factors including social deprivation, seasonal effects and alcohol consumption. Methods Use of record linked inpatient, mortality and primary care data for 10 589 hospitalised cases of acute pancreatitis between 1999 and 2010. Results The incidence of acute pancreatitis was 30.0 per 100 000 population overall, mortality was 6.4% at 60 days. Incidence increased significantly from 27.6 per 100 000 in 1999 to 36.4 in 2010 (average annual increase = 2.7% per year), there was little trend in mortality (0.2% average annual reduction). The largest increases in incidence were among women aged <35 years (7.9% per year) and men aged 35–44 (5.7%) and 45–54 (5.3%). Incidence was 1.9 times higher among the most deprived quintile of patients compared with the most affluent (3.9 times higher for alcoholic acute pancreatitis and 1.5 for gallstone acute pancreatitis). Acute pancreatitis was increased significantly during the Christmas and New Year weeks by 48% (95% CI = 24–77%) for alcoholic aetiology, but not for gallstone aetiology (9%). Alcoholic admissions were increased with higher consumption of spirits and beer, but not wine. Conclusions The study shows an elevated rate of alcoholic acute pancreatitis during the Christmas and New Year period. Acute pancreatitis continues to rise, most rapidly for young women, while alcoholic acute pancreatitis is linked strongly with social deprivation. PMID:23859492

  15. Managing alcohol withdrawal in the acutely ill hospitalized adult.

    PubMed

    Segatore, M; Adams, D; Lange, S

    1999-06-01

    Managing individuals with acute illness who are at high risk for alcohol withdrawal presents multiple challenges to the treatment teams caring for them. Following realization that management of this group was often characterized by severe withdrawal symptoms (delirium tremens, seizures and the need for leather restraints), a Task Force developed protocols to guide care. Its principal goal was to avoid cardiorespiratory and neurologic morbidities associated with severe withdrawal. The first 441 episodes of care treated after protocol implementation are described in this report. There were no instances of oversedation requiring pharmacological reversal or intubation, few individuals suffered seizures outside of the emergency department and the use of leather restraints declined dramatically. Outstanding issues arising from analysis include the necessity of subjecting the symptom severity instrument to rigorous psychometric study and reconsideration of the appropriateness of a symptom-triggered approach in treating this population. Our experience suggests that use of a nonprescriptive approach by educated and motivated nursing and medical staffs can reduce serious morbidity in this at-risk population. PMID:10846644

  16. Hazardous alcohol consumption and other barriers to antiviral treatment among hepatitis C positive people receiving opioid maintenance treatment

    Microsoft Academic Search

    Bianca Watson; KATHERINE M. CONIGRAVE; Cate Wallace; JOHN B. WHITFIELD; Friedrich Wurst; PAUL S. HABER

    2007-01-01

    Amongst people on opioid maintenance treatment (OMT), chronic hepatitis C (HCV) is common but infrequently treated. Numerous barriers, including misuse of alcohol may limit efforts at anti-viral treatment. The aim of this study was to define barriers, including alcohol misuse, to the effective treatment of HCV amongst OMT recipients. Ninety-four OMT patients completed the 3-item Alcohol Use Disorders Identification Test

  17. Acute alcohol effects on cognitive function in social drinkers: their relationship to drinking habits

    Microsoft Academic Search

    Ruth Weissenborn; Theodora Duka

    2003-01-01

      Abstract\\u000a \\u000a \\u000a Rationale. Several studies suggest that cognitive deficits seen in late stages of alcoholism are related to executive function. However,\\u000a little is known about the acute effects of alcohol on cognitive executive functions.\\u000a \\u000a \\u000a \\u000a \\u000a Aims. The present investigation examined the acute effects of a moderate alcohol dose on tests of planning and spatial working\\u000a memory as well as on tests of

  18. MATERNAL COFFEE AND ALCOHOL CONSUMPTION DURING PREGNANCY, PARENTAL SMOKING AND RISK OF CHILDHOOH ACUTE LEUKEMIA

    E-print Network

    Paris-Sud XI, Université de

    ACUTE LEUKEMIA Short title: Maternal coffee and alcohol consumption, parental smoking and childhood leukemia Category : Original article Condensed abstract : Maternal habits during pregnancy, as maternal smoking and maternal beverage consumption, were obtained for 280 cases of childhood acute leukemia and 280

  19. The Cumulative Effects of Acute Alcohol Consumption, Individual Differences and Situational Perceptions on Sexual Decision Making*

    PubMed Central

    ABBEY, ANTONIA; SAENZ, CHRISTOPHER; BUCK, PHILIP O.

    2015-01-01

    Objective Past alcohol administration research has produced mixed findings regarding the role of acute alcohol consumption on sexual decision making. The purpose of this study was to evaluate a more complex theoretical model that places alcohol's acute effects in context, through the inclusion of background measures as well as affective and cognitive responses to the specific situation. Method College students (90 men, 90 women) completed a survey that included measures of individual difference characteristics and past experiences; approximately 1 month later, they participated in an alcohol administration study. Participants were randomly assigned to one of three drink conditions (sober, placebo, alcohol), after which they read a story about a couple that wanted to have sex, but had no condoms available. Results In hierarchical multiple regression analyses, acute alcohol consumption significantly predicted participants’ perceived likelihood that they would have sex without a condom in such a situation; an earlier step included gender, impulsivity, self-reported alcohol expectancies, frequency of heavy drinking, lifetime number of sexual partners and frequency of condom use. There was no significant effect associated with the expectancy that one had consumed alcohol. Neither was there a significant interaction between drink condition and self-reported alcohol expectancies. Conclusions Through the inclusion of measures of individual differences and responses to the specific situation, this study provides a more nuanced understanding of the factors that affect college students’ sexual decision making, compared with laboratory studies that examine the effects of acute alcohol consumption in isolation. Alcohol consumption explained a significant yet relatively small amount of variance. Researchers need to consider the broader context to understand how intoxication influences sexual decision making. PMID:15830907

  20. Acute thrombocytopenia: An uncommon complication occurring following transarterial chemoembolization in a patient with neuroendocrine hepatic metastases

    PubMed Central

    XIE, PINGKUN; YUAN, ZHENG

    2015-01-01

    Neuroendocrine tumors are a group of carcinomas that secrete various polypeptides with hormonal activity. A significant percentage of patients already have hepatic metastases at the time of initial diagnosis, and 80–90% of these tumors are inoperable at the time of presentation. Transarterial chemoembolization (TACE) is the preferred approach for the management of neuroendocrine hepatic metastases. Although the technique is relatively safe, it is associated with several complications. The present study reported the case of a patient with neuroendocrine hepatic metastases who developed acute thrombocytopenia following TACE. To the best of our knowledge, acute thrombocytopenia occurring after TACE in a patient with neuroendocrine hepatic metastases has not been previously reported. In the present study, the hypothetical etiopathogenetic mechanisms were also discussed. PMID:26171007

  1. Sudden death of an alcoholic elderly man with acute esophageal necrosis (black esophagus).

    PubMed

    Unuma, Kana; Harada, Kazuki; Funakoshi, Takeshi; Uemura, Koichi

    2011-10-10

    We report a fatal case of acute esophageal necrosis (black esophagus) in an elderly male with alcohol abuse who was found dead with coffee-ground vomiting. A postmortem examination revealed severe anemia and marked black coloring of the esophagus from the upper to the bottom end. This was accompanied by histologic evidence of extensive mucosal necrosis. Alcohol abuse and esophagitis-related vomiting were both considered to be factors that led to the acute fatal esophageal necrosis. The cause of death was undetermined. We discuss the possible role of acute esophageal necrosis in the cause of sudden death. PMID:21684699

  2. Alcohol Worsens Acute Lung Injury by Inhibiting Alveolar Sodium Transport through the Adenosine A1 Receptor

    PubMed Central

    Urich, Daniela; Soberanes, Saul; Manghi, Tomas S.; Chiarella, Sergio E.; Chandel, Navdeep S.; Budinger, G. R. Scott; Mutlu, Gökhan M.

    2012-01-01

    Objective Alcohol intake increases the risk of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) and is associated with poor outcomes in patients who develop these syndromes. No specific therapies are currently available to treat or decrease the risk of ARDS in patients with alcoholism. We have recently shown increased levels of lung adenosine inhibit alveolar fluid clearance, an important predictor of outcome in patients with ARDS. We hypothesized that alcohol might worsen lung injury by increasing lung adenosine levels, resulting in impaired active Na+ transport in the lung. Methods We treated wild-type mice with alcohol administered i.p. to achieve blood alcohol levels associated with moderate to severe intoxication and measured the rate of alveolar fluid clearance and Na,K-ATPase expression in peripheral lung tissue and assessed the effect of alcohol on survival during exposure to hyperoxia. We used primary rat alveolar type II cells to investigate the mechanisms by which alcohol regulates alveolar Na+ transport. Results Exposure to alcohol reduced alveolar fluid clearance, downregulated Na,K-ATPase in the lung tissue and worsened hyperoxia-induced lung injury. Alcohol caused an increase in BAL fluid adenosine levels. A similar increase in lung adenosine levels was observed after exposure to hyperoxia. In primary rat alveolar type II cells alcohol and adenosine decreased the abundance of the Na,K-ATPase at the basolateral membrane via a mechanism that required activation of the AMPK. Conclusions Alcohol decreases alveolar fluid clearance and impairs survival from acute lung injury. Alcohol induced increases in lung adenosine levels may be responsible for reduction in alveolar fluid clearance and associated worsening of lung injury. PMID:22272351

  3. 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

  4. Hepatic stellate cell activation occurs in the absence of hepatitis in alcoholic liver disease and correlates with the severity of steatosis

    Microsoft Academic Search

    Helen L. Reeves; Alastair D. Burt; Susan Wood; Christopher P. Day

    1996-01-01

    Background\\/Aims: There is now overwhelming evidence that hepatic stellate cells are the principal cells involved in hepatic fibrogenesis. In several different forms of liver injury it has been demonstrated that they proliferate and undergo phenotypic transformation (activation) into matrix-producing, myofibroblast-like cells in response to necroinflammation, mediated in part, by Kupffer cell-derived factors. In alcoholic liver disease, however, the observation that

  5. Pathogenesis of liver cirrhosis in alcoholic patients: histological evidence for hepatitis C virus responsibility.

    PubMed

    Halimi, C; Dény, P; Gotheil, C; Trinchet, J C; Mal, F; Scavizzi, M; Beaugrand, M

    1991-12-01

    Hepatitis C virus (HCV) has been proposed to be a cofactor in the pathogenesis of cirrhosis in patients with chronic alcoholism. The demonstration of a different liver histological pattern in anti-HCV positive patients might provide additional evidence. We studied 164 patients with chronic alcoholism, and histologically proven cirrhosis. For all of them, serum samples were collected at the time of a liver biopsy and stored at -80 degrees C. Testing for anti-HCV antibodies was done using the Ortho Diagnostic Systems Anti-HCV ELISA test. Only reproducible results were considered positive. A semi-quantitative assessment of seven histological parameters was made independently on liver biopsy samples. In the study group, 29 patients (18%) had anti-HCV antibodies. When compared with anti-HCV negative patients, both groups had similar ALT and AST seric activities. Anti-HCV positive patients had a greater score of mononuclear cells infiltrate (0.71 +/- 0.57 vs 0.41 +/- 0.52; p less than 0.05) and a lesser score of alcoholic hepatitis (0.19 +/- 0.57 vs 0.74 +/- 0.74; p less than 0.005). The scores for steatosis, perisinusoidal and perinodular fibrosis, and hepatocellular necrosis were similar in the two groups. In anti-HCV positive patients, with a clearly positive recombinant immunobinding assay (RIBA, Chiron-Ortho Diagnostic Systems), a greater score for hepatic necrosis and a lesser one for fibrosis were demonstrated. Among the seven patients with active cirrhosis, six were anti-HCV positive. Therefore, HCV is likely to play a role in the pathogenesis of liver damage in a few patients with alcoholic cirrhosis, especially, those with active cirrhosis. PMID:1664014

  6. Clinical Factors and Viral Load Influencing Severity of Acute Hepatitis A

    PubMed Central

    Lee, Hyun Woong; Chang, Dong-Yeop; Moon, Hong Ju; Chang, Hye Young; Shin, Eui-Cheol; Lee, June Sung; Kim, Kyung-Ah; Kim, Hyung Joon

    2015-01-01

    Background and Aims Clinical manifestations of hepatitis A virus (HAV) infection vary from mild to fulminant hepatic failure (FHF) in adults. We investigated the relationship between laboratory findings, including viral load, and clinical outcomes in patients with acute hepatitis A (AHA) and evaluated predictive factors for severe acute hepatitis (s-AH). Methods We analyzed the clinical manifestations of AHA in 770 patients. Patients with a prothrombin time (PT) of less than 40% of normal were classified as s-AH and included 4 patients with FHF, 11 patients with acute renal failure, and 3 patients with prolonged jaundice (n = 128). Other patients were defined as mild acute hepatitis (m-AH) (n = 642). Serum samples were obtained from 48 patients with acute hepatitis A. Among them, 20 with s-AH, and 28 with m-AH, were tested for HAV RNA titer. Results In a multivariate analysis, age (HR = 1.042, P = 0.041), peak creatinine (HR = 4.014, P = 0.001), bilirubin (HR = 1.153, P = 0.003), alanine aminotransferase (ALT) (HR = 1.001, P<0.001), initial lactate dehydrogenase (LDH) (HR = 1.000, P = 0.045) and total cholesterol (HR = 0.978, P<0.001) were independent factors for s-AH. Serum HAV RNA was detected in 20/20 (100%) patients with s-AH and 22/28 (78.6%) patients with m-AH. In a multivariate analysis of the 48 patients who were tested for HAV RNA, peak ALT (HR = 1.001, P = 0.004) and HAV RNA titer (HR = 2.076, P = 0.012) were independent factors for s-AH. Conclusions Clinical factors including age, peak creatinine, bilirubin, ALT, initial LDH and total cholesterol were independent factors for s-AH in a multivariate analysis. In particular, HAV load strongly correlated with the severity of hepatitis A. PMID:26090677

  7. Efficacy of Lamivudine or Entecavir on Acute Exacerbation of Chronic Hepatitis B

    PubMed Central

    Kanda, Tatsuo; Shinozaki, Masami; Kamezaki, Hidehiro; Wu, Shuang; Nakamoto, Shingo; Arai, Makoto; Fujiwara, Keiichi; Goto, Nobuaki; Imazeki, Fumio; Yokosuka, Osamu

    2012-01-01

    Background/Aims: Spontaneous acute exacerbation of chronic hepatitis B virus (HBV) infection occasionally occurs in its natural history, sometimes leading rapidly to fatal hepatic failure. We compared the effects of lamivudine (LAM) with those of entecavir (ETV) treatments in acute exacerbation of chronic hepatitis B with 500 IU/L or higher alanine aminotransferase (ALT) levels. Methods: Thirty-four patients with acute exacerbation were consecutively treated with LAM /ETV. Their clinical improvements were compared. Results: Among LAM-treated and ETV-treated patients, none showed a reduction of <1 log IU/mL in HBV DNA after 1 or 3 months of treatment. Initial virological response, defined as a reduction of 4 log IU/mL in HBV DNA at 6 months, with LAM and ETV, respectively, was 83.3% and 100%. One LAM patient developed hepatic encephalopathy, but all patients in both groups survived. Twelve months after treatment, 41.6% of 24 LAM group patients switched to another drug or added adefovir to their treatment due to the emergence of LAM-resistant mutants. On the other hand, patients receiving ETV did not need to change drugs. Conclusions: ETV appears to be as effective as LAM in the treatment of patients with acute exacerbation of chronic hepatitis B. Clinicians should carefully start to treat these patients as soon as possible. PMID:22211086

  8. Leptin administration restores the altered adipose and hepatic expression of aquaglyceroporins improving the non-alcoholic fatty liver of ob/ob mice

    PubMed Central

    Rodríguez, Amaia; Moreno, Natalia R.; Balaguer, Inmaculada; Méndez-Giménez, Leire; Becerril, Sara; Catalán, Victoria; Gómez-Ambrosi, Javier; Portincasa, Piero; Calamita, Giuseppe; Soveral, Graça; Malagón, María M.; Frühbeck, Gema

    2015-01-01

    Glycerol is an important metabolite for the control of lipid accumulation in white adipose tissue (WAT) and liver. We aimed to investigate whether exogenous administration of leptin improves features of non-alcoholic fatty liver disease (NAFLD) in leptin-deficient ob/ob mice via the regulation of AQP3 and AQP7 (glycerol channels mediating glycerol efflux in adipocytes) and AQP9 (aquaglyceroporin facilitating glycerol influx in hepatocytes). Twelve-week-old male wild type and ob/ob mice were divided in three groups as follows: control, leptin-treated (1?mg/kg/d) and pair-fed. Leptin deficiency was associated with obesity and NAFLD exhibiting an AQP3 and AQP7 increase in WAT, without changes in hepatic AQP9. Adipose Aqp3 and hepatic Aqp9 transcripts positively correlated with markers of adiposity and hepatic steatosis. Chronic leptin administration (4-weeks) was associated with improved body weight, whole-body adiposity, and hepatosteatosis of ob/ob mice and to a down-regulation of AQP3, AQP7 in WAT and an up-regulation of hepatic AQP9. Acute leptin stimulation in vitro (4-h) induced the mobilization of aquaglyceroporins towards lipid droplets (AQP3) and the plasma membrane (AQP7) in murine adipocytes. Our results show that leptin restores the coordinated regulation of fat-specific AQP7 and liver-specific AQP9, a step which might prevent lipid overaccumulation in WAT and liver in obesity. PMID:26159457

  9. Leptin administration restores the altered adipose and hepatic expression of aquaglyceroporins improving the non-alcoholic fatty liver of ob/ob mice.

    PubMed

    Rodríguez, Amaia; Moreno, Natalia R; Balaguer, Inmaculada; Méndez-Giménez, Leire; Becerril, Sara; Catalán, Victoria; Gómez-Ambrosi, Javier; Portincasa, Piero; Calamita, Giuseppe; Soveral, Graça; Malagón, María M; Frühbeck, Gema

    2015-01-01

    Glycerol is an important metabolite for the control of lipid accumulation in white adipose tissue (WAT) and liver. We aimed to investigate whether exogenous administration of leptin improves features of non-alcoholic fatty liver disease (NAFLD) in leptin-deficient ob/ob mice via the regulation of AQP3 and AQP7 (glycerol channels mediating glycerol efflux in adipocytes) and AQP9 (aquaglyceroporin facilitating glycerol influx in hepatocytes). Twelve-week-old male wild type and ob/ob mice were divided in three groups as follows: control, leptin-treated (1?mg/kg/d) and pair-fed. Leptin deficiency was associated with obesity and NAFLD exhibiting an AQP3 and AQP7 increase in WAT, without changes in hepatic AQP9. Adipose Aqp3 and hepatic Aqp9 transcripts positively correlated with markers of adiposity and hepatic steatosis. Chronic leptin administration (4-weeks) was associated with improved body weight, whole-body adiposity, and hepatosteatosis of ob/ob mice and to a down-regulation of AQP3, AQP7 in WAT and an up-regulation of hepatic AQP9. Acute leptin stimulation in vitro (4-h) induced the mobilization of aquaglyceroporins towards lipid droplets (AQP3) and the plasma membrane (AQP7) in murine adipocytes. Our results show that leptin restores the coordinated regulation of fat-specific AQP7 and liver-specific AQP9, a step which might prevent lipid overaccumulation in WAT and liver in obesity. PMID:26159457

  10. Metadoxine in the treatment of acute and chronic alcoholism: a review.

    PubMed

    Addolorato, G; Ancona, C; Capristo, E; Gasbarrini, G

    2003-01-01

    Alcohol abuse and alcoholism are responsible for a wide variety of medical problems. The pharmaco-therapeutic aspect of alcoholism includes the use of drugs, with different actions and objectives. Among them, metadoxine seems to be of interest. Metadoxine is able to accelerate the elimination of alcohol from the blood and tissues, to help restore the functional structure of the liver and to relieve neuro-psychological disorders associated with alcohol intoxication. Metadoxine also seems to be safe; in more than 15 years of post-marketing surveillance only minor aspecific and reversible events were monitored in patients exposed to the treatment. In this review the preclinical and clinical results obtained using metadoxine in acute and chronic alcohol intoxication are reported. PMID:14611722

  11. Albumin dialysis improves hepatic encephalopathy and decreases circulating phenolic aromatic amino acids in patients with alcoholic hepatitis and severe liver failure

    PubMed Central

    Parés, Albert; Deulofeu, Ramón; Cisneros, Laura; Escorsell, Angels; Salmerón, Joan Manuel; Caballería, Joan; Mas, Antoni

    2009-01-01

    Introduction The aim of this study was to assess the effects of albumin dialysis on hepatic encephalopathy and circulating levels of amino acids in severe alcoholic hepatitis. Methods The study was carried out in nine patients with severe alcoholic hepatitis and four with primary biliary cirrhosis treated with the molecular adsorbent recirculating system. Besides standard liver function tests, circulating levels of ammonia, total, branched chain and aromatic amino acids, the presence and severity of hepatic encephalopathy, and number connection test were measured before and after each treatment. Results There were eight episodes of encephalopathy in patients with alcoholic hepatitis. Albumin dialysis was associated with significant improvement in encephalopathy (p = 0.02), and a decrease in total amino acid levels (2490 ± 152 ?M to 2229 ± 114 ?M, p < 0.001). Moreover, the Fischer's ratio, which was significantly lower in patients with alcoholic hepatitis (1.32 ± 0.08) than in controls (3.20 ± 0.16), increased by 17% after albumin dialysis (p < 0.02) because of a significant decrease in phenolic aromatic amino acids (193 ± 17 ?M to 165 ± 9 ?M, p = 0.04). No differences were observed in circulating ammonia. Changes in phenolic aromatic amino acids and the Fischer's ratio were more prominent in patients with encephalopathy and higher bilirubin removal. Albumin dialysis did not significantly affect the amino acid profile in the controls. Conclusions Albumin dialysis results in a significant decrease in circulating phenolic aromatic amino acids and improvement of hepatic encephalopathy in patients with severe liver failure. PMID:19175915

  12. Mallory-Denk Body (MDB) formation modulates Ufmylation expression epigenetically in alcoholic hepatitis (AH) and non-alcoholic steatohepatitis (NASH).

    PubMed

    Liu, Hui; Gong, Ming; French, Barbara A; Li, Jun; Tillman, Brittany; French, Samuel W

    2014-12-01

    Promoter CpG island hypermethylation is an important mechanism for inactivating key cellular enzymes that mediate epigenetic processes in hepatitis-related hepatocellular carcinoma (HCC). The ubiquitin-fold modifier 1 (Ufm1) conjugation pathway (Ufmylation) plays an essential role in protein degradation, protein quality control and signal transduction. Previous studies showed that the Ufmylation pathway was downregulated in alcoholic hepatitis (AH), non-alcoholic steatohepatitis (NASH) and in mice fed DDC, resulting in the formation of Mallory-Denk Bodies (MDBs). In this study, we further discovered that betaine, a methyl donor, fed together with DDC significantly prevents the increased expression of Ufmylation in drug-primed mice fed DDC. Betaine significantly prevented transcript silencing of Ufm1, Uba5 and UfSP1 where MDBs developed and also prevented the increased expression of FAT10 and LMP7 caused by DDC re-fed mice. Similar downregulation of Ufmylation was observed in multiple AH and NASH biopsies which had formed MDBs. The DNA methylation levels of Ufm1, Ufc1 and UfSP1 in the promoter CpG region were significantly increased both in AH and NASH patients compared to normal subjects. DNA (cytosine-5-)-methyltransferase 1 (DNMT1) and DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) mRNA levels were markedly upregulated in AH and NASH patients, implying that the maintenance of Ufmylation methylation might be mediated by DNMT1 and DNMT3B together. These data show that MDB formation results from Ufmylation expression epigenetically in AH and NASH patients. Promoter CpG methylation may be a major mechanism silencing Ufmylation expression. PMID:25290169

  13. Infection and the progression of hepatic encephalopathy in acute liver failure

    Microsoft Academic Search

    Javier Vaquero; Julie Polson; Chuhan Chung; Irene Helenowski; Frank V. Schiodt; Joan Reisch; William M. Lee; Andres T. Blei

    2003-01-01

    Background & Aims:Progression of hepatic encephalopathy (HE) is a major determinant of outcome in acute liver failure (ALF). Our aim was to identify predictive factors of worsening HE, including the relation of encephalopathy with the systemic inflammatory response (SIRS) and infection. Methods:We included 227 consecutive patients with stage I-II HE prospectively enrolled in the U.S. Acute Liver Failure Study. Univariate

  14. Acute versus chronic alcohol consumption in acetaminophen-induced hepatotoxicity

    Microsoft Academic Search

    Lars E. Schmidt; Kim Dalhoff; Henrik Enghusen Poulsen

    2002-01-01

    The aim of this study was to determine by multivariate analysis how alcohol and other factors affect the clinical course and outcome in patients with acetaminophen (paracetamol) poisoning. A total of 645 consecutive patients admitted from 1994 to 2000 with single-dose acetaminophen poisoning were studied, giving special attention to alcohol history, time between overdose and intravenous N-acetylcysteine (NAC) treatment (“time

  15. Sporadic acute hepatitis E of a 47-year-old man whose pet cat was positive for antibody to hepatitis E virus

    Microsoft Academic Search

    Akiko Kuno; Kenichi Ido; Norio Isoda; Yoshiaki Satoh; Kazunori Ono; Shin Satoh; Hideaki Inamori; Kentaro Sugano; Nobuyuki Kanai; Tsutomu Nishizawa; Hiroaki Okamoto

    2003-01-01

    We encountered a patient with sporadic acute hepatitis E who had not traveled to areas endemic for hepatitis E virus (HEV) infection and may have been infected in Japan. The patient was a 47-year-old male who had no history of blood transfusion or contact with travelers to hepatitis E-endemic regions or unspecified individuals. The disease presented with general malaise, fever,

  16. Effect of Acute Self-Limited Hepatitis C Virus (HCV) Superinfection on Hepatitis B Virus (HBV)Related Cirrhosis. Virological Features of HBV–HCV Dual Infection

    Microsoft Academic Search

    Norio Akuta; Fumitaka Suzuki; Mariko Kobayashi; Akihito Tsubota; Yoshiyuki Suzuki; Tetsuya Hosaka; Takashi Someya; Masahiro Kobayashi; Satoshi Saitoh; Yasuji Arase; Kenji Ikeda; Hiromitsu Kumada

    2004-01-01

    We investigated the virological impact of acute hepatitis C virus (HCV) superinfection on two patients with hepatitis B virus (HBV)-related cirrhosis. In both patients, chronic HBV-infection persisted while acute HCV infection resolved spontaneously. HBV DNA was transiently suppressed in both patients but increased with HCV resolution. In Case 1 (HBeAg-positive; wild type of basic core promoter [BCP] and precore [PreC]),

  17. Absence of Perilipin 2 Prevents Hepatic Steatosis, Glucose Intolerance and Ceramide Accumulation in Alcohol-Fed Mice

    PubMed Central

    Carr, Rotonya M.; Peralta, Giselle; Yin, Xiaoyan; Ahima, Rexford S.

    2014-01-01

    Background Perilipin 2 (Plin2) is a lipid droplet protein that has roles in both lipid and glucose homeostasis. An increase in Plin2 in liver is associated with the development of steatosis, glucose intolerance, and ceramide accumulation in alcoholic liver disease. We investigated the role of Plin2 on energy balance and glucose and lipid homeostasis in wildtype and Plin2 knockout (Plin2KO) mice chronically fed a Lieber-DeCarli liquid ethanol or control diet for six weeks. Methods We performed in vivo measurements of energy intake and expenditure; body composition; and glucose tolerance. After sacrifice, liver was dissected for histology and lipid analysis. Results We found that neither genotype nor diet had a significant effect on final weight, body composition, or energy intake between WT and Plin2KO mice fed alcohol or control diets. Additionally, alcohol feeding did not affect oxygen consumption or carbon dioxide production in Plin2KO mice. We performed glucose tolerance testing and observed that alcohol feeding failed to impair glucose tolerance in Plin2KO mice. Most notably, absence of Plin2 prevented hepatic steatosis and ceramide accumulation in alcohol-fed mice. These changes were related to downregulation of genes involved in lipogenesis and triglyceride synthesis. Conclusions Plin2KO mice chronically fed alcohol are protected from hepatic steatosis, glucose intolerance, and hepatic ceramide accumulation, suggesting a critical pathogenic role of Plin2 in experimental alcoholic liver disease. PMID:24831094

  18. Influences of Situational Factors and Alcohol Expectancies on Sexual Desire and Arousal Among Heavy-Episodic Drinking Women: Acute Alcohol Intoxication and Condom Availability

    PubMed Central

    George, William H.; Nguyen, Hong V.; Heiman, Julia R.; Davis, Kelly Cue; Norris, Jeanette

    2013-01-01

    Although studies suggest that alcohol increases women’s sexual desire, no studies to our knowledge have examined the effects of acute alcohol intoxication on women’s sexual desire. The majority of research examining alcohol’s effects on sexual arousal in women suggests that alcohol increases self-reported arousal. In an alcohol administration study in which women projected themselves into an eroticized scenario depicting a consensual sexual encounter with a new male partner, we examined the effects of alcohol and condom condition on women’s sexual desire and arousal. The moderating effects of sex-related alcohol expectancies were also examined. Results revealed that alcohol intoxication was related to less desire to engage in sex with a new partner and condom presence was related to more desire. Alcohol interacted with sexual disinhibition alcohol expectancies, indicating that more expectancy endorsement was associated with greater sexual desire and self-reported arousal in the alcohol condition, but not the control condition. Condom condition had no effect on self-reported sexual arousal. The present research suggests that sexual desire merits research attention in non-clinical samples, and experimental methodology can provide valuable information about alcohol’s influence on women’s sexual desire, thus advancing our understanding of this relationship beyond cross-sectional correlations. The current findings also provide evidence that sex-related alcohol expectancies may play an important role in alcohol-involved sexual experiences including desire and arousal. PMID:23661324

  19. Curative effect of lauromacrogol and absolute ethyl alcohol injection guided by ultrasound on simplex hepatic cyst.

    PubMed

    Xue, Jie; Geng, Xianhui

    2015-03-01

    This research aims to analyze the curative effect and security of lauromacrogol injection and absolute ethyl alcohol treating simplex hepatic cyst respectively. The simplex hepatic cyst patients were divided into lauromacrogol group (86 cases, research group) and absolute ethyl alcohol group (80 cases, control group). Both two groups received sclerotherapy of thoracic drainage under ultrasonic guidance and the curative effect and untoward effect were observed. The result showed there was no hemorrhage or infection within two groups. During the therapeutic process, 45 patients (56.3%) suffered from pain at different degrees and 23 cases were found with symptom of drunkenness in control group, while the patients in the research group were found with no obvious discomfort. A week after treatment, 23 patients (25.0%) in control group still remained to have swelling pain at upper right stomach, while there were only 9 in treatment group (10.5%), and the difference was of statistical significance (X(2)=6.037, P<0.05). through 6 months of follow-up visit after the operation, we found the cure rate of lauromacrogol group was 94.6% and absolute ethyl alcohol was 92.6%, and the difference between these two groups was of no statistical significance (P>0.05). The results showed that, in the treatment of cystosclerosis with absolute ethyl alcohol injection under ultrasonic guidance, some patients suffered pain and the symptom of drunkenness at different degrees, whereas, lauromacrogol was effective with no untoward effects, therefore it is worthy of clinical popularization and application. PMID:25796160

  20. A Rare Case of Icteric Acute Hepatitis C Infection Acquired Through Intranasal Methamphetamine Use

    PubMed Central

    Yimam, Kidist K.; Frederick, R. Todd; Swenson, Sara L.

    2014-01-01

    Most patients with acute hepatitis C (HCV) infections are asymptomatic, while 15% present with jaundice. Intranasal drug use can uncommonly transmit HCV via contaminated instruments and nasal epithelial breakdown. Given a 15% prevalence of HCV infection in chronic methamphetamine users, recognition of potential transmission routes is important to target prevention and screening efforts in this population.

  1. Use of iron colloid-enhanced MRI for study of acute radiation-induced hepatic injury

    SciTech Connect

    Suto, Yuji; Ametani, Masaki; Kato, Takashi; Hashimoto, Masayuki; Kamba, Masayuki; Sugihara, Syuji; Ohta, Yoshio [Tottori Univ. School of Medicine, Yonago (Japan)] [Tottori Univ. School of Medicine, Yonago (Japan)

    1996-03-01

    We present a case with acute radiation-induced hepatic injury using chondroitin sulfate iron colloid (CSIC)-enhanced MRI. Uptake of CSIC was decreased in the irradiated portion of the liver. CSIC-enhanced MRI is useful for obtaining information on the function of the reticuloendothelial system and demarcates between irradiated and nonirradiated zones. 18 refs., 3 figs

  2. Infection and the Progression of Hepatic Encephalopathy in Acute Liver Failure

    Microsoft Academic Search

    JAVIER VAQUERO; JULIE POLSON; CHUHAN CHUNG; IRENE HELENOWSKI; FRANK V. SCHIODT; JOAN REISCH; WILLIAM M. LEE; ANDRES T. BLEI

    2003-01-01

    Background & Aims: Progression of hepatic encephalop- athy (HE) is a major determinant of outcome in acute liver failure (ALF). Our aim was to identify predictive factors of worsening HE, including the relation of en- cephalopathy with the systemic inflammatory response (SIRS) and infection. Methods: We included 227 consec- utive patients with stage I-II HE prospectively enrolled in the U.S.

  3. Massive infiltration of liver by metastatic adenocarcinoma: a rare cause of acute hepatic failure.

    PubMed

    Varghese, Joy; Jayanthi, Venkataraman; Patra, Susma; Rela, Mohamed

    2012-09-01

    Acute liver cell failure can occur by diffuse infiltration of malignant cells in liver parenchyma. The malignant cells might be either primary hepatocellular carcinoma or metastatic liver disease. Mostly, CT abdomen with intravenous contrast fails to detect liver malignancy. We report a case of liver metastasis masquerading as fulminant hepatic failure. PMID:25755446

  4. Integrated epidethiological system for acute viral hepatitis in Italy ( SEIEVA ): Description and preliminary results

    Microsoft Academic Search

    A. Mele; F. Rosmini; A. Zampieri; O. N. Gill

    1986-01-01

    An integrated epidemiological system for the surveillance of acute viral hepatitis SEIEVA which linked notifications to available serology results and used a standard risk factor questionnaire is described. Results of over 1300 cases reported by 35 participating local health units (USL's) during the first 18 months of the programme are presented.

  5. Post-Acute Coronary Syndrome Alcohol Abuse: Prospective Evaluation in the ERICO Study

    PubMed Central

    Morilha, Abner; Karagulian, Samuel; Lotufo, Paulo A.; Santos, Itamar S.; Benseñor, Isabela M.; Goulart, Alessandra C.

    2015-01-01

    Background Some studies have indicated alcohol abuse as one of the contributors to the development of cardiovascular disease, particularly coronary heart disease. However, this relationship is controversial. Objective To investigate the relationship between post-acute coronary syndrome (ACS) alcohol abuse in the Acute Coronary Syndrome Registry Strategy (ERICO Study). Methods 146 participants from the ERICO Study answered structured questionnaires and underwent laboratory evaluations at baseline, 30 days and 180 days after ACS. The Alcohol Use Disorders Identification Test (AUDIT) was applied to assess harmful alcohol consumption in the 12 months preceding ACS (30 day-interview) and six months after that. Results The frequencies of alcohol abuse were 24.7% and 21.1% in the 12 months preceding ACS and six months after that, respectively. The most significant cardiovascular risk factors associated with high-risk for alcohol abuse 30 days after the acute event were: male sex (88.9%), current smoking (52.8%) and hypertension (58.3%). Six months after the acute event, the most significant results were replicated in our logistic regression, for the association between alcohol abuse among younger individuals [35-44 year-old multivariate OR: 38.30 (95% CI: 1.44-1012.56) and 45-54 year-old multivariate OR: 10.10 (95% CI: 1.06-96.46)] and for smokers [current smokers multivariate OR: 51.09 (95% CI: 3.49-748.01) and past smokers multivariate OR: 40.29 (95% CI: 2.37-685.93)]. Conclusion Individuals younger than 54 years and smokers showed a significant relation with harmful alcohol consumption, regardless of the ACS subtype. PMID:25945467

  6. Acute and residual interactive effects of repeated administrations of oral methamphetamine and alcohol in humans

    Microsoft Academic Search

    Matthew G. Kirkpatrick; Erik W. Gunderson; Frances R. Levin; Richard W. Foltin; Carl L. Hart

    Although methamphetamine and alcohol are commonly used together in a binge-like pattern, there is a dearth of empirical data\\u000a investigating the repeated effects of this drug combination. The current study examined acute and residual mood, performance,\\u000a and physiological effects of methamphetamine alone, alcohol alone, and the combination. Nine adult male volunteers completed\\u000a this 20-day within-participant, residential laboratory study. During four

  7. Prevalence and types of drug-resistant variants in Chinese patients with acute hepatitis B.

    PubMed

    Su, Feifei; Dai, Jianyi; Yang, Shoufeng; Jiang, Xiangao; Cui, Xiaoya; Ning, Hongye; Li, Junhua; Huang, Mohe

    2015-09-01

    The presence of therapy-associated hepatitis B virus (HBV) variants is the main drawback of antiviral therapy for HBV infection. Moreover, drug-resistant variants are more insensitive to a second agent and more therapy-associated mutations will be present. To apply better nucleos(t)ide analogues (NA) and reduce the occurrence of resistance, the prevalence and types of drug-resistant mutations in acute hepatitis B patients were investigated in this study. One hundred three HBV DNA-positive patients with symptomatic acute hepatitis B that were observed from 2011 to 2013 were enrolled. Direct polymerase chain reaction sequencing was used firstly to screen HBV reverse-transcriptase domain to detect HBV mutants. Five lamivudine-resistant variants were identified. Clonal sequencing was performed for 5 resistance-positive samples and 10 other random samples. Interestingly, all detected samples harbored drug-resistant mutations, although with different percentage. Thirteen harbored lamivudine-related alone (five) or together with other NA related mutations (five with adefovir, one with entecavir, and one with telbivudine), and two of them harbored adefovir-related mutations. Also, mutations associated with four currently used NA were all detected, and the frequency is in accordance with the popularity of NA used in clinical practice. These data suggest that drug-resistant variants are present in patients with acute hepatitis B and NA should be applied more carefully for chronic hepatitis B patients developed from acute hepatitis B. J. Med. Virol. 87:1527-1531, 2015. © 2015 Wiley Periodicals, Inc. PMID:26032700

  8. Factors Associated with Alcohol Consumption in Hepatitis B Carriers: A Nationwide Study in the Republic of Korea

    PubMed Central

    Park, Boyoung; Jung, Kyu-Won; Oh, Chang-Mo; Choi, Kui Son; Suh, Mina; Jun, Jae Kwan

    2014-01-01

    This study was conducted to investigate the prevalence of alcohol consumption and identify the sociodemographic factors associated with alcohol consumption among individuals with hepatitis B virus(HBV) infection. We used data from the Korean National Health and Nutrition Examination Surveys, a nationwide survey conducted between 2007 and 2011. “Monthly alcohol consumption” was defined as having consumed alcohol at least once per month during the past year, and “high-risk alcohol consumption” was defined as having consumed alcohol twice or more per week and, for males, having consumed at least 60 g of alcohol on one occasion or, for females, having consumed at least 40 g of alcohol on more than one occasion. The prevalence of monthly alcohol consumption was 53.2%, and that of high-risk alcohol consumption was 11.8% among HBV carriers. Less education was associated with both monthly and high-risk alcohol consumption(OR?=?1.75 [95% CI?=?1.02?3.02] for monthly alcohol consumption among those with less than a high school education; OR?=?2.48 [95% CI?=?1.19?5.17] for high-risk alcohol consumption among those with less than a high school education and OR?=?2.02 [95% CI?=?1.12?3.64] among those with a high school education). Additionally, smoking and being male increased the risk of alcohol consumption, and older age and having a normal body mass index decreased the risk. HBV carriers who were less educated, overweight, and smokers were more likely to consume alcohol or meet criteria for high-risk drinking. Health policies and intervention programs aimed at promoting a generally healthy lifestyle in HBV carriers should consider educational inequalities and alcohol consumption. PMID:25387237

  9. Heart rate turbulence during acute alcohol withdrawal syndrome

    Microsoft Academic Search

    Thomas Jochum; Steffen Schulz; Marion Schein; Rico Schröder; Andreas Voss; Karl-Jürgen Bär

    BackgroundAlcohol withdrawal syndrome is associated with an increased incidence of cardiac arrhythmias and sudden cardiac death. Heart rate turbulence (HRT) parameters were applied during withdrawal to estimate cardiac regulation during treatment with clomethiazole.

  10. Quantitative Proteomics Identifies Host Factors Modulated during Acute Hepatitis E Virus Infection in the Swine Model

    PubMed Central

    Rogée, Sophie; Le Gall, Morgane; Chafey, Philippe; Bouquet, Jérôme; Cordonnier, Nathalie; Frederici, Christian

    2014-01-01

    ABSTRACT Hepatitis E virus (HEV) causes acute enterically transmitted hepatitis. In industrialized countries, it is a zoonotic disease, with swine being the major reservoir of human HEV contamination. The occurrence and severity of the disease are variable, with clinical symptoms ranging from asymptomatic to self-limiting acute hepatitis, chronic infection, or fulminant hepatitis. In the absence of a robust cell culture system or small-animal models, the HEV life cycle and pathological process remain unclear. To characterize HEV pathogenesis and virulence mechanisms, a quantitative proteomic analysis was carried out to identify cellular factors and pathways modulated during acute infection of swine. Three groups of pigs were inoculated with three different strains of swine HEV to evaluate the possible role of viral determinants in pathogenesis. Liver samples were analyzed by a differential proteomic approach, two-dimensional difference in gel electrophoresis, and 61 modulated proteins were identified by mass spectroscopy. The results obtained show that the three HEV strains replicate similarly in swine and that they modulate several cellular pathways, suggesting that HEV impairs several cellular processes, which can account for the various types of disease expression. Several proteins, such as heterogeneous nuclear ribonucleoprotein K, apolipoprotein E, and prohibitin, known to be involved in other viral life cycles, were upregulated in HEV-infected livers. Some differences were observed between the three strains, suggesting that HEV's genetic variability may induce variations in pathogenesis. This comparative analysis of the liver proteome modulated during infection with three different strains of HEV genotype 3 provides an important basis for further investigations on the factors involved in HEV replication and the mechanism of HEV pathogenesis. IMPORTANCE Hepatitis E virus (HEV) is responsible for acute hepatitis, with clinical symptoms ranging from asymptomatic to self-limiting acute hepatitis, chronic infection, or fulminant hepatitis. In industrialized countries, HEV is considered an emerging zoonotic disease, with swine being the principal reservoir for human contamination. The viral and cellular factors involved in the replication and/or pathogenesis of HEV are still not fully known. Here we report that several cellular pathways involved in cholesterol and lipid metabolism or cell survival were modulated during HEV infection in the swine model. Moreover, we observed a difference between the different swine strains, suggesting that HEV's genetic variability could play a role in pathogenesis. We also identified some proteins known to be involved in other viral cycles. Our study provides insight into the mechanisms modulated during HEV infection and constitutes a useful reference for future work on HEV pathogenesis and virulence. PMID:25320303

  11. Assessment of alcohol consumption among hepatitis C-positive people receiving opioid maintenance treatment using direct ethanol metabolites and self-report: a pilot study.

    PubMed

    Wurst, Friedrich M; Haber, Paul S; Wiesbeck, Gerhard; Watson, Bianca; Wallace, Cate; Whitfield, John B; Halter, Claudia; Weinmann, Wolfgang; Conigrave, Katherine M

    2008-09-01

    This study was conducted to identify the alcohol consumption among hepatitis C-positive people receiving opioid maintenance therapy using self-report and biomarkers. A total of 49 people (28 male, 21 female) were hepatitis C virus (HCV) positive and were included. The alcohol use disorder identification test (AUDIT) and self-reported ethanol intake in the last 28 days were assessed. In addition to gamma-glutamyl-transferase (GGT) and mean corpuscular volume (MCV), ethyl glucuronide (EtG) and ethyl sulphate (EtS) were determined in serum and urine (UEtG, UEtS, SEtG) using liquid chromatography/tandem mass-spectroscopy (LC/MS-MS) with deuterated internal standards. Abstinence from alcohol was reported for the last 28 days by 13 participants and for the last 7 days by 22. AUDIT was > 8 in 27 cases. The maximum values were 34.8 mg/l for UEtG, 5.3 mg/l for UEtS and 0.15 for SEtG. Among the 19 UEtG positives, 8 had not reported any ethanol intake in the 7 days prior to the study. Six participants reported intake of up to 320 g of ethanol in the last 7 days, but were negative for SEtG, UEtG and UEtS. Self-reported ethanol intake in the last 28 days correlated with AUDIT score (r = 0.733, P < 0.001), with the direct ethanol metabolites and MCV. In this population, abstinence and episodic heavy drinking are more common than in the general population. Episodic heavy drinking is a significant cause of acute risk in this population. Results from biomarker testing could indicate cases of under- as well as over-reporting of alcohol consumption. Further research on the diagnostic accuracy of direct ethanol metabolites, including the use of phosphatidylethanol (PEth), in this setting is needed. PMID:17711559

  12. Percutaneous Alcohol Sclerotherapy of Simple Hepatic Cysts. Results From a Multicentre Survey in Italy

    PubMed Central

    Montorsi, Marco; Torzilli, Guido; Fumagalli, Uberto; Bona, Stefano; Rosati, Riccardo; de Simone, Matilde; Rovati, Vittorio; Mosca, Franco; Filice, Carlo

    1994-01-01

    The increased use of Ultrasonography (US) has led to increased detection of simple hepatic cysts. For symptomatic cysts treatment is necessary. Until some years ago surgery was the only therapy. We have treated a large number of patients with Percutaneous Alcohol Sclerotherapy (PAS) and evaluated retrospectively the efficacy of this approach. Data on 21 patients with symptomatic simple hepatic cysts were reviewed retrospectively. Cysts had a mean diameter of 9 cm (range: 7–15 cm). PAS was always performed under local anesthesia and US guidance. 25% of the volume was replaced with 95% ethanol and then completely aspirated after 20–30 minutes. No complications or deaths occurred. In all patients symptoms disappeared after treatment. In 15 out of 21 cases there was no evidence of residual cyst on US, computed tomography (CT) or magnetic resonance (MRI). In 6 patients with shorter follow-up, cysts showed a mean reduction in diameter of 50%. The mean follow-up was 18 months (range 6–60 months). We conclude that PAS is easy with low risk for the patients and with good long-term results; it should therefore become the procedure of choice for simple hepatic cysts. PMID:7880778

  13. Protective effect of calpain inhibitor N-acetyl-L-leucyl-L-leucyl-L-norleucinal on acute alcohol consumption related cardiomyopathy.

    PubMed

    Kartkaya, Kazim; Kanbak, Güngör; O?lakç?, Ay?egül; Buruko?lu, Dilek; Ozer, Mehmet Caner

    2014-10-01

    Excessive alcohol consumption and alcoholism cause medical problems with high mortality and morbidity rates. In this study we aimed to decrease the alcohol related tissue damage by inhibiting calpain activation which plays an important role in apoptosis and necrosis, in rats with cardiomyopathy induced by acute alcohol consumption. Male Sprague-Dawley rats were separated into four groups (control, vehicle, alcohol and alcohol + inhibitor) with 10 rats in each. Control group received isocaloric maltose while vehicle group received isocaloric maltose with DMSO, and alcohol group received 8 g/kg absolute ethanol by gavage. Inhibitor group received 20 mg/kg calpain inhibitor 1 intraperitonally prior to alcohol administration. Calpain activities, cathepsin L levels and cytochrome c release rates were significantly increased in alcohol group compared to control group (p < 0.05). Serum CK MB and BNP levels of alcohol group were excessively increased compared to control group (respectively p < 0.001 and p < 0.01). Serum BNP levels of alcohol + inhibitor group were significantly (p < 0.05) decreased compared to alcohol group. In addition to these, histological evaluation of light microscope images and the results of DNA fragmentation and immunohistochemical caspase-3 activity results showed significant improvement of these parameters in alcohol + inhibitor group compared to alcohol group. Results of our biochemical and histological evaluation results revealed that the calpain inhibitor N-acetyl-leu-leu-norleucinal may have an ameliorating effect on acute alcohol consumption related cardiac tissue damage due to its effects on cell death pathways. PMID:24996291

  14. Cytotoxic T lymphocytes and natural killer cells display impaired cytotoxic functions and reduced activation in patients with alcoholic hepatitis.

    PubMed

    Støy, Sidsel; Dige, Anders; Sandahl, Thomas Damgaard; Laursen, Tea Lund; Buus, Christian; Hokland, Marianne; Vilstrup, Hendrik

    2015-02-15

    The dynamics and role of cytotoxic T lymphocytes (CTLs), natural killer (NK) cells, and NKT cells in the life-threatening inflammatory disease alcoholic hepatitis is largely unknown. These cells directly kill infected and damaged cells through, e.g., degranulation and interferon-? (IFN?) production, but cause tissue damage if overactivated. They also assist tissue repair via IL-22 production. We, therefore, aimed to investigate the frequency, functionality, and activation state of such cells in alcoholic hepatitis. We analyzed blood samples from 24 severe alcoholic hepatitis patients followed for 30 days after diagnosis. Ten healthy abstinent volunteers and 10 stable abstinent alcoholic cirrhosis patients were controls. Using flow cytometry we assessed cell frequencies, NK cell degranulation capacity following K562 cell stimulation, activation by natural killer group 2 D (NKG2D) expression, and IL-22 and IFN? production. In alcoholic hepatitis we found a decreased frequency of CTLs compared with healthy controls (P < 0.001) and a similar trend for NK cells (P = 0.089). The NK cell degranulation capacity was reduced by 25% compared with healthy controls (P = 0.02) and by 50% compared with cirrhosis patients (P = 0.04). Accordingly, the NKG2D receptor expression was markedly decreased on NK cells, CTLs, and NKT cells (P < 0.05, all). The frequencies of IL-22-producing CTLs and NK cells were doubled compared with healthy controls (P < 0.05, all) but not different from cirrhosis patients. This exploratory study for the first time showed impaired cellular cytotoxicity and activation in alcoholic hepatitis. This is unlikely to cause hepatocyte death but may contribute toward the severe immune incompetence. The results warrant detailed and mechanistic studies. PMID:25501547

  15. Reduced hepatic mitochondrial respiration following acute high-fat diet is prevented by PGC-1? overexpression

    PubMed Central

    Morris, E. Matthew; Jackman, Matthew R.; Meers, Grace M. E.; Johnson, Ginger C.; Lopez, Jordan L.; MacLean, Paul S.

    2013-01-01

    Changes in substrate utilization and reduced mitochondrial respiratory capacity following exposure to energy-dense, high-fat diets (HFD) are putatively key components in the development of obesity-related metabolic disease. We examined the effect of a 3-day HFD on isolated liver mitochondrial respiration and whole body energy utilization in obesity-prone (OP) rats. We also examined if hepatic overexpression of peroxisomal proliferator-activated receptor-? coactivator-1? (PGC-1?), a master regulator of mitochondrial respiratory capacity and biogenesis, would modify liver and whole body responses to the HFD. Acute, 3-day HFD (45% kcal) in OP rats resulted in increased daily energy intake, energy balance, weight gain, and adiposity, without an increase in liver triglyceride (triacylglycerol) accumulation. HFD-fed OP rats also displayed decreased whole body substrate switching from the dark to the light cycle, which was paired with reductions in hepatic mitochondrial respiration of multiple substrates in multiple respiratory states. Hepatic PGC-1? overexpression was observed to protect whole body substrate switching, as well as maintain mitochondrial respiration, following the acute HFD. Additionally, liver PGC-1? overexpression did not alter whole body dietary fatty acid oxidation but resulted in greater storage of dietary free fatty acids in liver lipid, primarily as triacylglycerol. Together, these data demonstrate that a short-term HFD can result in a decrease in metabolic flexibility and hepatic mitochondrial respiratory capacity in OP rats that is completely prevented by hepatic overexpression of PGC-1?. PMID:24091599

  16. 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

  17. Superselective arterial embolisation with a liquid polyvinyl alcohol copolymer in patients with acute gastrointestinal haemorrhage

    Microsoft Academic Search

    Markus Lenhart; Christian Paetzel; Michael Sackmann; Hans Schneider; Ernst Michael Jung; Andreas G. Schreyer; Stefan Feuerbach; Niels Zorger

    2010-01-01

    Objectives  To evaluate the results of emergency embolisation in acute arterial bleeding of the gastrointestinal tract with a liquid polyvinyl\\u000a alcohol copolymer from two centres.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  We retrospectively analysed 16 cases (15 patients) of acute arterial bleeding of the gastrointestinal tract where emergency\\u000a embolotherapy was performed by using the copolymer when acute haemorrhage was not treatable with endoscopic techniques alone.\\u000a Cause of

  18. 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.

  19. Acute Ethanol Effects on Brain Activation in Low- and High-Level Responders to Alcohol

    PubMed Central

    Trim, Ryan S.; Simmons, Alan N.; Tolentino, Neil J.; Hall, Shana A.; Matthews, Scott C.; Robinson, Shannon K.; Smith, Tom L.; Padula, Claudia B.; Paulus, Martin P.; Tapert, Susan F.; Schuckit, Marc A.

    2013-01-01

    Background A low level of response (LR) to alcohol is an important endophenotype associated with an increased risk for alcoholism. However, little is known about how neural functioning may differ between individuals with low and high LRs to alcohol. This study examined whether LR group effects on neural activity varied as a function of acute alcohol consumption. Methods 30 matched high- and low-LR pairs (N=60 healthy young adults) were recruited from the University of California, San Diego and administered a structured diagnostic interview and laboratory alcohol challenge followed by two fMRI sessions under placebo and alcohol conditions, in randomized order. Task performance and BOLD response contrast to high relative to low working memory load in an event-related visual working memory (VWM) task was examined across 120 fMRI sessions. Results Both LR groups performed similarly on the VWM task across conditions. A significant LR group by condition interaction effect was observed in inferior frontal and cingulate regions, such that alcohol attenuated the LR group differences found under placebo (p<.05). The LR group by condition effect remained even after controlling for cerebral blood flow, age, and typical drinking quantity. Conclusions Alcohol had differential effects on brain activation for low and high LR individuals within frontal and cingulate regions. These findings represent an additional step in the search for physiological correlates of a low LR, and identify brain regions that may be associated with the low LR response. PMID:20477775

  20. Acute Alcohol Administration and Placebo Effectiveness in Older Moderate Drinkers: Influences on Cognitive Performance*

    PubMed Central

    Gilbertson, Rebecca; Prather, Robert; Jo Nixon, Sara

    2010-01-01

    Objective: Placebo effectiveness and subsequent influence on cognitive performance were investigated in older moderate drinkers (ages 50–69; N = 30; 15 men) following acute alcohol administration. Method: Double-blind, placebo-controlled alcohol administration techniques were designed to produce peak breath alcohol concentration levels consistent with an episode of social drinking (?40 mg/100 ml). Cognitive performance, measured via a covert attentional processing task, was assessed. Participants were also asked to rate their perceived levels of intoxication and impairment. Results: The placebo beverage was effective in older moderate drinkers, with 63% of participants who received placebo reporting that they received alcohol. Placebo beverage effectiveness influenced cognitive performance. Participants who received placebo, but reported they received alcohol, demonstrated slower reaction times on the covert attentional processing task, similar to those receiving alcohol. Placebo effects did not influence accuracy on the covert attentional processing task or self-reported measures of intoxication and impairment. As expected, participants who received alcohol had less accuracy on the covert attentional processing task and more self-reported impairment and intoxication than those who received placebo, regardless of placebo effectiveness. Conclusions: These results suggest that belief of having received a moderate dose of alcohol has an effect on reaction time similar to that of its pharmacological effect in older moderate drinkers. Although placebo effects are not novel, these findings suggest that cognitive processes are differentially affected. The study of moderate doses and more complex real-world tasks is an important next step. PMID:20409427

  1. Is rat liver affected by non-alcoholic steatosis more susceptible to the acute toxic effect of thioacetamide?

    PubMed Central

    Ku?era, Otto; Lotková, Halka; Sta?ková, Pavla; Podhola, Miroslav; Roušar, Tomáš; Mezera, Vojt?ch; ?ervinková, Zuzana

    2011-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic condition of the liver in the western world. There is only little evidence about altered sensitivity of steatotic liver to acute toxic injury. The aim of this project was to test whether hepatic steatosis sensitizes rat liver to acute toxic injury induced by thioacetamide (TAA). Male Sprague–Dawley rats were fed ad libitum a standard pelleted diet (ST-1, 10% energy fat) and high-fat gelled diet (HFGD, 71% energy fat) for 6 weeks and then TAA was applied intraperitoneally in one dose of 100 mg/kg. Animals were sacrificed in 24-, 48- and 72-h interval after TAA administration. We assessed the serum biochemistry, the hepatic reduced glutathione, thiobarbituric acid reactive substances, cytokine concentration, the respiration of isolated liver mitochondria and histopathological samples (H+E, Sudan III, bromodeoxyuridine [BrdU] incorporation). Activities of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase and concentration of serum bilirubin were significantly higher in HFGD groups after application of TAA, compared to ST-1. There were no differences in activities of respiratory complexes I and II. Serum tumour necrosis factor alpha at 24 and 48 h, liver tissue interleukin-6 at 72 h and transforming growth factor ?1 at 24 and 48 h were elevated in TAA-administrated rats fed with HFGD, but not ST-1. TAA-induced centrilobular necrosis and subsequent regenerative response of the liver were higher in HFGD-fed rats in comparison with ST-1. Liver affected by NAFLD, compared to non-steatotic liver, is more sensitive to toxic effect of TAA. PMID:21410800

  2. Is rat liver affected by non-alcoholic steatosis more susceptible to the acute toxic effect of thioacetamide?

    PubMed

    Ku?era, Otto; Lotková, Halka; Sta?ková, Pavla; Podhola, Miroslav; Roušar, Tomáš; Mezera, Vojt?ch; Cervinková, Zuzana

    2011-08-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic condition of the liver in the western world. There is only little evidence about altered sensitivity of steatotic liver to acute toxic injury. The aim of this project was to test whether hepatic steatosis sensitizes rat liver to acute toxic injury induced by thioacetamide (TAA). Male Sprague-Dawley rats were fed ad libitum a standard pelleted diet (ST-1, 10% energy fat) and high-fat gelled diet (HFGD, 71% energy fat) for 6 weeks and then TAA was applied intraperitoneally in one dose of 100 mg/kg. Animals were sacrificed in 24-, 48- and 72-h interval after TAA administration. We assessed the serum biochemistry, the hepatic reduced glutathione, thiobarbituric acid reactive substances, cytokine concentration, the respiration of isolated liver mitochondria and histopathological samples (H+E, Sudan III, bromodeoxyuridine [BrdU] incorporation). Activities of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase and concentration of serum bilirubin were significantly higher in HFGD groups after application of TAA, compared to ST-1. There were no differences in activities of respiratory complexes I and II. Serum tumour necrosis factor alpha at 24 and 48 h, liver tissue interleukin-6 at 72 h and transforming growth factor ?1 at 24 and 48 h were elevated in TAA-administrated rats fed with HFGD, but not ST-1. TAA-induced centrilobular necrosis and subsequent regenerative response of the liver were higher in HFGD-fed rats in comparison with ST-1. Liver affected by NAFLD, compared to non-steatotic liver, is more sensitive to toxic effect of TAA. PMID:21410800

  3. Acute withdrawal, protracted abstinence and negative affect in alcoholism: Are they linked?

    PubMed Central

    Heilig, M.; Egli, M.; Crabbe, J.C.; Becker, H.C.

    2012-01-01

    The role of withdrawal-related phenomena in development and maintenance of alcohol addiction remains under debate. A “self-medication” framework postulates that emotional changes are induced by a history of alcohol use, persist into abstinence, and are a major factor in maintaining alcoholism. This view initially focused on negative emotional states during early withdrawal: these are pronounced, occur in the vast majority of alcohol dependent patients, and are characterized by depressed mood and elevated anxiety. This concept lost popularity with the realization that, in most patients, these symptoms abate over 3 – 6 weeks of abstinence, while relapse risk persists long beyond this period. More recently, animal data have established that a prolonged history of alcohol dependence induces more subtle neuroadaptations. These confer altered emotional processing that persists long into protracted abstinence. The resulting behavioral phenotype is characterized by excessive voluntary alcohol intake and increased behavioral sensitivity to stress. Emerging human data support the clinical relevance of negative emotionality for protracted abstinence and relapse. These developments prompt a series of research questions: 1) Are processes observed during acute withdrawal, while transient in nature, mechanistically related to those that remain during protracted abstinence? 2) Is susceptibility to negative emotionality in acute withdrawal in part due to heritable factors, similar to what animal models have indicated for susceptibility to physical aspects of withdrawal? 3) To what extent is susceptibility to negative affect that persists into protracted abstinence heritable? PMID:20148778

  4. Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine

    PubMed Central

    Vilela, Luciano Rezende; Gomides, Lindisley Ferreira; David, Bruna Araújo; Antunes, Maísa Mota; Diniz, Ariane Barros; Moreira, Fabrício de Araújo; Menezes, Gustavo Batista

    2015-01-01

    Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. The most severe and common complications are seizures, ischemic strokes, myocardial infarction, and acute liver injury. Here, we demonstrated that acute cocaine intoxication promoted seizure along with acute liver damage in mice, with intense inflammatory infiltrate. Considering the protective role of the endocannabinoid system against cell toxicity, we hypothesized that treatment with an anandamide hydrolysis inhibitor, URB597, or with a phytocannabinoid, cannabidiol (CBD), protects against cocaine toxicity. URB597 (1.0?mg/kg) abolished cocaine-induced seizure, yet it did not protect against acute liver injury. Using confocal liver intravital microscopy, we observed that CBD (30?mg/kg) reduced acute liver inflammation and damage induced by cocaine and prevented associated seizure. Additionally, we showed that previous liver damage induced by another hepatotoxic drug (acetaminophen) increased seizure and lethality induced by cocaine intoxication, linking hepatotoxicity to seizure dynamics. These findings suggest that activation of cannabinoid system may have protective actions on both liver and brain induced by cocaine, minimizing inflammatory injury promoted by cocaine, supporting its further clinical application in the treatment of cocaine abuse. PMID:25999668

  5. HEV identified in serum from humans with acute hepatitis and in sewage of animal origin in Spain

    Microsoft Academic Search

    Sonia Pina; Maria Buti; Montserrat Cotrina; Joan Piella; Rosina Girones

    2000-01-01

    Background\\/Aims: Hepatitis E virus (HEV) is an enterically transmitted pathogen that appears sporadically in non-endemic countries. We studied HEV as a causal agent of acute hepatitis cases in the Spanish population, and the role of pigs as an animal reservoir.Methods: The presence of HEV-RNA was analysed by nested polymerase chain reaction in 37 serum samples from patients with acute viral

  6. Effects of Perioperative Protease Inhibitor on Inflammatory Cytokines and Acute-Phase Proteins in Patients with Hepatic Resection

    Microsoft Academic Search

    S. Ambiru; M. Miyazaki; K. Sasada; H. Ito; F. Kimura; K. Nakagawa; H. Shimizu; K. Ando; N. Nakajima

    2000-01-01

    Aim: The objective of this study was to examine the effects of perioperative administration of ulinastatin, or urinary trypsin inhibitor (UTI), on inflammatory cytokines and acute-phase proteins induced by inflammatory cytokines in patients who had undergone hepatic resection. Method: Twenty patients admitted to the hospital for hepatic resection were equally randomized to one of two groups: the UTI group, those

  7. Rhabdomyolysis, acute renal failure, and multiple focal neuropathies after drinking alcohol soaked with centipede.

    PubMed

    Wang, I-Kuan; Hsu, Shih-Pin; Chi, Ching-Chi; Lee, Kam-Fai; Lin, Paul Yann; Chang, Hsueh-Wen; Chuang, Feng-Rong

    2004-01-01

    Many Chinese like to drink alcohol soaked with creatures for promoting health. This study reports a 49-year-old male who presented with multiple focal neuropathies of the upper limbs, coagulopathy, erythematous swelling of the bilateral upper extremities and trunk with bullous skin lesions, and rhabdomyolysis associated with acute renal failure after drinking alcohol soaked with centipede. Soaking a centipede, Scolopendra subspinipes mutilans, in 53% alcohol, produced the wine. Supportive treatment was administered, and the skin lesions and renal failure improved with subsequent neurologic deficit during the week following initial presentation. Alcohol binge or immobilization was the likely cause of neuropathy, bullous skin lesions and rhabdomyolysis in the patient. However, there is a possibility that centipede venom also contributed to the illness in this patient. PMID:15083930

  8. High Risk of Hepatitis B Reactivation among Patients with Acute Myeloid Leukemia

    PubMed Central

    Chen, Chien-Yuan; Huang, Sheng-Yi; Cheng, Aristine; Chou, Wen-Chien; Yao, Ming; Tang, Jih-Luh; Tsay, Woei; Sheng, Wang-Huei; Tien, Hwei-Fang

    2015-01-01

    Background Hepatitis B virus (HBV) infections are common and associated with significant morbidity and mortality in cancer patients. However, the incidence and risk factors of HBV reactivation in patients with acute myeloid leukemia (AML) are rarely investigated. Methods AML patients followed-up at the National Taiwan University Hospital between 2006 and 2012 were analyzed. The clinical characteristics and laboratory data were retrospectively reviewed. Results Four hundred and ninety patients comprising 265 men and 225 women were studied. The median age was 52 years (range, 18 - 94). Chronic HBV carriage was documented at the time of leukemia diagnosis in 57 (11.6%) patients. Forty-six (80.7%) of the 57 HBV carriers received prophylaxis with anti-HBV agents. Sixteen HBV carriers (28.1%) developed hepatitis B reactivation during or after chemotherapy, including 7 patients who had discontinued antiviral therapy. The incidence of hepatitis B reactivation among AML patients with HBV carriage was 9.5 per 100 person-years. Prophylaxis with anti-HBV agents significantly decreased the risk of hepatitis B reactivation among HBV carriers (13% vs. 61%, p<0.001). Four (2.8%) of 142 patients with initial positive anti-HBsAb and anti-HBcAb experienced hepatitis B reactivation and lost their protective anti-HBsAb. Multivariate analysis revealed that diabetes mellitus (p=0.008, odds ratio (OR) = 2.841, 95% confident interval (CI): 0.985-8.193) and carriage of HBsAg (p<0.001, OR=36.878, 95% CI: 11.770-115.547) were independent risk factors for hepatitis B reactivation in AML patients. Conclusions Hepatitis B reactivation is not uncommon in the HBsAg positive AML patients. Prophylaxis with anti-HBV agent significantly decreased the risk of hepatitis B reactivation. PMID:25973905

  9. Alcohol Impairs Interferon Signaling and Enhances Full Cycle Hepatitis C Virus JFH-1 Infection of Human Hepatocytes

    PubMed Central

    Ye, Li; Wang, Shihong; Wang, Xu; Zhou, Yu; Li, Jieliang; Persidsky, Yuri; Ho, Wenzhe

    2010-01-01

    Alcohol drinking and hepatitis C virus (HCV) infection frequently coexist in patients with chronic liver disease. There is limited information, however, about the impact of alcohol on host cell innate immunity and full cycle replication of HCV. This study investigated whether alcohol impairs the intracellular innate immunity in human hepatocytes, promoting HCV infection and replication. Alcohol treatment of human hepatocytes before, during and after viral infection significantly enhanced full cycle HCV replication. Alcohol suppressed intracellular expression of type I interferons (IFN-?/?) in human hepatocytes. Investigation of the mechanisms responsible for the alcohol action revealed that alcohol inhibited the expression of the IFN regulatory factors (IRF-5 and IRF-7), and signal transducer and activator of transcription (STAT-1 and STAT-2), the key positive regulators in type I IFN signaling pathway. In addition, alcohol induced the expression of suppressors of cytokine signaling (SOCS-2 and SOCS-3), the key negative regulators of IFN-?/? expression. These in vitro findings suggest that alcohol, through modulating the expression of key regulators in IFN signaling pathway, inhibits type I IFN-based intracellular innate immunity in hepctocytes, which may contribute to the chronicity of HCV infection and the poor efficacy of IFN-?-based therapy. PMID:20646875

  10. Differentiation of acute and chronic hepatitis B in IgM anti-HBc positive patients

    PubMed Central

    Park, Ji Won; Kwak, Kyeong Min; Kim, Sung Eun; Jang, Myoung Kuk; Kim, Dong Joon; Lee, Myung Seok; Kim, Hyoung Su; Park, Choong Kee

    2015-01-01

    AIM: To identify the factors that differentiate acute hepatitis B (AHB) from chronic hepatitis B with acute exacerbation (CHB-AE). METHODS: From 2004 to 2013, a total of 82 patients (male n = 52, 63.4%; female n = 30, 36.6%) with clinical features of acute hepatitis with immunoglobulin M antibodies to the hepatitis B core antigen (IgM anti-HBc) were retrospectively enrolled and divided into two groups; AHB (n = 53) and CHB-AE (n = 29). The AHB group was defined as patients without a history of hepatitis B virus (HBV) infection before the episode and with loss of hepatitis B surface antigen within 6 mo after onset of acute hepatitis. Biochemical and virological profiles and the sample/cutoff (S/CO) ratio of IgM anti-HBc were compared to determine the differential diagnostic factors. RESULTS: The multivariate analysis demonstrated that, the S/CO ratio of IgM anti-HBc and HBV DNA levels were meaningful factors. The S/CO ratio of IgM anti-HBc was significantly higher in the AHB group, while the HBV DNA level was significantly higher in the CHB-AE group. The optimal cutoff values of IgM anti-HBc and HBV DNA levels for differentiating the two conditions were 8 S/CO ratio and 5.5 log10 IU/mL, respectively. The sensitivity and specificity were 96.2% and 89.7% for the S/CO ratio of IgM anti-HBc and 81.1% and 72.4% for HBV DNA levels, respectively. The area under receiver operating characteristic curves of both the S/CO ratio of IgM anti-HBc and HBV DNA levels were not significantly different (0.933 vs 0.844, P = 0.105). When combining IgM anti-HBc and HBV DNA, the diagnostic power significantly improved compared to HBV DNA alone (P = 0.0056). The combination of these factors yielded a sensitivity and specificity of 98.1% and 86.2%, respectively. CONCLUSION: The combination of the S/CO ratio of IgM anti-HBc and HBV DNA levels was a useful tool for differentiating AHB from CHB-AE in patients with positive IgM anti-HBc. PMID:25852281

  11. Acute Alcohol Intoxication Suppresses the Pulmonary ELR-Negative CXC Chemokine Response to Lipopolysaccharide

    PubMed Central

    Happel, Kyle I.; Rudner, Xiaowen; Quinton, Lee J.; Movassaghi, Jennifer L.; Clark, Charles; Odden, Anthony R.; Zhang, Ping; Bagby, Gregory J.; Nelson, Steve; Shellito, Judd E.

    2007-01-01

    Alcohol abuse impairs the pulmonary immune response to infection and increases the morbidity and mortality of bacterial pneumonia. Acute alcohol intoxication suppresses lung expression of CXC chemokines bearing the Glu-Leu-Arg motif (ELR+) following lipopolysaccharide (LPS) challenge, but its effect on the structurally-related ELR- CXC chemokines, which attract T cells, is unknown. We therefore investigated the effect of acute alcohol intoxication on the pulmonary response to intratracheal (i.t.) LPS challenge for the ELR- CXC chemokines monokine induced by gamma (MIG or CXCL9), interferon-inducible protein 10 (IP-10 or CXCL10), and interferon-inducible T cell alpha chemoattractant (I-TAC or CXCL11). Male C57BL/6 or C3H/HeN mice were given an intraperitoneal injection of ethanol (3.0g/kg) or PBS 30 min before i.t. LPS challenge. Chemokine mRNA transcripts were measured at 0, 2, 6, and 16 h. Acute alcohol intoxication inhibited the lung’s expression of all three chemokine genes in response to LPS. Lung IFN-? mRNA was also inhibited by acute intoxication over the same time course. The in vitro effect of ethanol on chemokine secretion was further studied in the MH-S alveolar macrophage cell line. IP-10, MIG, and I-TAC in response to LPS were enhanced by exogenous IFN-?, and these responses were blunted by exposure to ethanol. Alcohol exposure did not affect MH-S cell NF-kB p65 nuclear localization during challenge, despite dose-dependent inhibition of Erk 1/2 phosphorylation. In addition, phospho-STAT1 was not decreased in the presence of acute ethanol, thereby indicating acute intoxication does not affect IFN-? signaling in MH-S cells. Recruitment of CD3+ T cells into the alveolar space 4 days after LPS challenge was moderately impaired by acute ethanol intoxication. These results implicate acute ethanol intoxication as a significant inhibitor of lymphocyte chemoattractant expression during pulmonary inflammation. PMID:17889309

  12. Acute liver failure secondary to hepatic infiltration: a single centre experience of 18 cases

    Microsoft Academic Search

    D Rowbotham; J Wendon; R Williams

    1998-01-01

    Background—Acute liver failure (ALF) secondary to malignant infiltration of the liver is rare and is diagnosed often only after death.Aims—To determine diagnostic factors and particular clinical patterns of illness.Methods—Review of case notes from all patients with ALF secondary to hepatic infiltration admitted to this unit over an 18 year period (1978–1995).Results—From a total of 4020 admissions, 18 patients were identified

  13. Acute cholestatic hepatitis induced by bupropion prescribed as pharmacological support to stop smoking. A case report

    Microsoft Academic Search

    D. Alvaro; A. Onetti-Muda; R. Moscatelli; A. F. Attili

    2001-01-01

    We report the first case of acute cholestatic hepatitis induced by bupropion. This antidepressant was taken by a 49-year-old female as adjuvant treatment to stop smoking. After 20 days of bupropion, the patient presented a symptomatology characterized by asthenia, nausea and scleral icterus and biochemical analyses showed a dramatic increase in direct bilirubin (up to 28 mg\\/dl) and transaminases (up

  14. Autoimmune reaction to a liver specific membrane antigen during acute viral hepatitis.

    PubMed Central

    Cochrane, A M; Moussouros, A; Smith, A; Thomson, A D; Eddleston, A L; Williams, R

    1976-01-01

    Lymphocyte cytotoxicity for isolated hepatocytes has been demonstrated in 93% of cases of acute viral hepatitis tested within two weeks of the onset of symptoms. The frequency of cytotoxicity during this time was similar for HBsAg positive and negative cases. However, after this time it was significantly higher in HBsAg positive than negative cases, 90% and 25% respectively (P less than 0-01). Cytotoxicity was found in B-cell, but not T-cell, enriched fractions of lymphocytes, compatible with an antibody-dependent K-cell mediated reaction. In two cases the assay remained positive on retesting six months later, and follow-up liver biopsies showed the features of chronic aggressive hepatitis. These findings suggest that, in addition to the known immunological reactions against viral antigens that occur during the acute phase of viral hepatitis, an autoimmune reaction directed against a liver specific protein is also initiated; and if this reaction persists then chronic hepatitis may develop. PMID:61905

  15. A Histologic Scoring System for Prognosis of Patients With Alcoholic Hepatitis

    PubMed Central

    Altamirano, José; Miquel, Rosa; Katoonizadeh, Aezam; Abraldes, Juan G; Duarte-Rojo, Andrés; Louvet, Alexandre; Augustin, Salvador; Mookerjee, Rajeshwar P.; Michelena, Javier; Smyrk, Thomas C.; Buob, David; Leteurtre, Emmanuelle; Rincón, Diego; Ruiz, Pablo; García-Pagán, Juan Carlos; Guerrero-Marquez, Carmen; Jones, Patricia D.; Barritt, A. Sidney; Arroyo, Vicente; Bruguera, Miquel; Bañares, Rafael; Ginès, Pere; Caballería, Juan; Roskams, Tania; Nevens, Frederik; Jalan, Rajiv; Mathurin, Philippe; Shah, Vijay H.; Bataller, Ramón

    2014-01-01

    Background & Aims There is no histologic classification system to determine prognoses of patients with alcoholic hepatitis (AH). We identified histologic features associated with disease severity and created a histologic scoring system to predict short-term (90 day) mortality. Methods We analyzed data from 121 patients admitted to the Liver Unit (Hospital Clinic, Barcelona, Spain) from January 2000 through January 2008 with features of AH, and developed a histologic scoring system to determine risk of death using logistic regression. The system was tested and updated in a test set of 96 patients from 5 academic centers in the US and Europe, and a semi-quantitative scoring system was developed, called the alcoholic hepatitis histologic score (AHHS). The system was validated in an independent set of 109 patients. Inter-observer agreement was evaluated by weighted statistic analysis. Results Degree of fibrosis, neutrophil infiltration, type of bilirubinostasis, and presence mega-mitochondria were independently associated with 90 day mortality. We used these 4 parameters to develop the AHHS to identify patients with low (0–3 points), moderate (4–5 points), and high (6–9 points) risks of death within 90 days (3%, 19%, and 51%, respectively; P<.0001). The AHHS estimated 90 day mortality in the training and test sets with an area under the receiver operating characteristic value of 0.77 (95% confidence interval, 0.71–0.83). Inter-rate agreement values were 0.65 for fibrosis, 0.86 for bilirubinostasis, 0.60 for neutrophil infiltration, and 0.46 for megamitochondria. Interestingly, the type of bilirubinostasis predicted the development of bacterial infections. Conclusions We identified histologic features associated with severity of AH and developed a patient classification system that might be used in clinical decision making. PMID:24440674

  16. Sustained hyperresponsiveness of dendritic cells is associated with spontaneous resolution of acute hepatitis C.

    PubMed

    Pelletier, Sandy; Bédard, Nathalie; Said, Elias; Ancuta, Petronela; Bruneau, Julie; Shoukry, Naglaa H

    2013-06-01

    Some studies have reported that dendritic cells (DCs) may be dysfunctional in a subset of patients with chronic hepatitis C virus (HCV) infection. However, the function of DCs during acute HCV infection and their role in determining infectious outcome remain elusive. Here, we examined the phenotype and function of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) during acute HCV infection. Three groups of injection drug users (IDUs) at high risk of HCV infection were studied: an uninfected group, a group with acute HCV infection with spontaneous resolution, and a group with acute infection with chronic evolution. We examined the frequency, maturation status, and cytokine production capacity of DCs in response to the Toll-like receptor 4 (TLR4) and TLR7/8 ligands lipopolysaccharide (LPS) and single-stranded RNA (ssRNA), respectively. Several observations could distinguish HCV-negative IDUs and acute HCV resolvers from patients with acute infection with chronic evolution. First, we observed a decrease in the frequency of mature CD86(+), programmed death-1 receptor ligand-positive (PDL1(+)), and PDL2(+) pDCs. This phenotype was associated with the increased sensitivity of pDCs from resolvers and HCV-negative IDUs versus the group with acute infection with chronic evolution to ssRNA stimulation in vitro. Second, LPS-stimulated mDCs from resolvers and HCV-negative IDUs produced higher levels of cytokines than mDCs from the group with acute infection with chronic evolution. Third, mDCs from all patients with acute HCV infection, irrespective of their outcomes, produced higher levels of cytokines during the early acute phase in response to ssRNA than mDCs from healthy controls. However, this hyperresponsiveness was sustained only in spontaneous resolvers. Altogether, our results suggest that the immature pDC phenotype and sustained pDC and mDC hyperresponsiveness are associated with spontaneous resolution of acute HCV infection. PMID:23576504

  17. Sustained Hyperresponsiveness of Dendritic Cells Is Associated with Spontaneous Resolution of Acute Hepatitis C

    PubMed Central

    Pelletier, Sandy; Bédard, Nathalie; Said, Elias; Ancuta, Petronela; Bruneau, Julie

    2013-01-01

    Some studies have reported that dendritic cells (DCs) may be dysfunctional in a subset of patients with chronic hepatitis C virus (HCV) infection. However, the function of DCs during acute HCV infection and their role in determining infectious outcome remain elusive. Here, we examined the phenotype and function of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) during acute HCV infection. Three groups of injection drug users (IDUs) at high risk of HCV infection were studied: an uninfected group, a group with acute HCV infection with spontaneous resolution, and a group with acute infection with chronic evolution. We examined the frequency, maturation status, and cytokine production capacity of DCs in response to the Toll-like receptor 4 (TLR4) and TLR7/8 ligands lipopolysaccharide (LPS) and single-stranded RNA (ssRNA), respectively. Several observations could distinguish HCV-negative IDUs and acute HCV resolvers from patients with acute infection with chronic evolution. First, we observed a decrease in the frequency of mature CD86+, programmed death-1 receptor ligand-positive (PDL1+), and PDL2+ pDCs. This phenotype was associated with the increased sensitivity of pDCs from resolvers and HCV-negative IDUs versus the group with acute infection with chronic evolution to ssRNA stimulation in vitro. Second, LPS-stimulated mDCs from resolvers and HCV-negative IDUs produced higher levels of cytokines than mDCs from the group with acute infection with chronic evolution. Third, mDCs from all patients with acute HCV infection, irrespective of their outcomes, produced higher levels of cytokines during the early acute phase in response to ssRNA than mDCs from healthy controls. However, this hyperresponsiveness was sustained only in spontaneous resolvers. Altogether, our results suggest that the immature pDC phenotype and sustained pDC and mDC hyperresponsiveness are associated with spontaneous resolution of acute HCV infection. PMID:23576504

  18. Acute cholestatic hepatitis caused by amoxicillin/clavulanate.

    PubMed

    Beraldo, Daniel Oliveira; Melo, Joanderson Fernandes; Bonfim, Alexandre Vidal; Teixeira, Andrei Alkmim; Teixeira, Ricardo Alkmim; Duarte, André Loyola

    2013-12-14

    Amoxicillin/clavulanate is a synthetic penicillin that is currently commonly used, especially for the treatment of respiratory and cutaneous infections. In general, it is a well-tolerated oral antibiotic. However, amoxicillin/clavulanate can cause adverse effects, mainly cutaneous, gastrointestinal, hepatic and hematologic, in some cases. Presented here is a case report of a 63-year-old male patient who developed cholestatic hepatitis after recent use of amoxicillin/clavulanate. After 6 wk of prolonged use of the drug, he began to show signs of cholestatic icterus and developed severe hyperbilirubinemia (total bilirubin > 300 mg/L). Diagnostic investigation was conducted by ultrasonography of the upper abdomen, serum tests for infection history, laboratory screening of autoimmune diseases, nuclear magnetic resonance (NMR) of the abdomen with bile duct-NMR and transcutaneous liver biopsy guided by ultrasound. The duration of disease was approximately 4 mo, with complete resolution of symptoms and laboratory changes at the end of that time period. Specific treatment was not instituted, only a combination of anti-emetic (metoclopramide) and cholestyramine for pruritus. PMID:24379601

  19. Acute interstitial nephritis with acetaminophen and alcohol intoxication

    Microsoft Academic Search

    Lauren L Fruchter; Iakovina Alexopoulou; Keith K Lau

    2011-01-01

    Drug-induced acute interstitial nephritis (AIN) represents a growing cause of renal failure in current medical practice. While\\u000a antimicrobials and non-steroidal anti-inflammatory drugs are typically associated with drug-induced AIN, few reports have\\u000a been made on the involvement of other analgesics. We report our experience in managing a 17-year-old female with AIN and subsequent\\u000a renal injury following an acetaminophen overdose in conjunction

  20. Amphiregulin activates human hepatic stellate cells and is upregulated in non alcoholic steatohepatitis

    PubMed Central

    McKee, Chad; Sigala, Barbara; Soeda, Junpei; Mouralidarane, Angelina; Morgan, Maelle; Mazzoccoli, Gianluigi; Rappa, Francesca; Cappello, Francesco; Cabibi, Daniela; Pazienza, Valerio; Selden, Claire; Roskams, Tania; Vinciguerra, Manlio; Oben, Jude A.

    2015-01-01

    Amphiregulin (AR) involvement in liver fibrogenesis and hepatic stellate cells (HSC) regulation is under study. Non-alcoholic fatty liver disease (NAFLD) and its more severe form non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular cancer (HCC). Our aim was to investigate ex vivo the effect of AR on human primary HSC (hHSC) and verify in vivo the relevance of AR in NAFLD fibrogenesis. hHSC isolated from healthy liver segments were analyzed for expression of AR and its activator, TNF-? converting enzyme (TACE). AR induction of hHSC proliferation and matrix production was estimated in the presence of antagonists. AR involvement in fibrogenesis was also assessed in a mouse model of NASH and in humans with NASH. hHSC time dependently expressed AR and TACE. AR increased hHSC proliferation through several mitogenic signaling pathways such as EGFR, PI3K and p38. AR also induced marked upregulation of hHSC fibrogenic markers and reduced hHSC death. AR expression was enhanced in the HSC of a murine model of NASH and of severe human NASH. In conclusion, AR induces hHSC fibrogenic activity via multiple mitogenic signaling pathways, and is upregulated in murine and human NASH, suggesting that AR antagonists may be clinically useful anti-fibrotics in NAFLD. PMID:25744849

  1. Alcohol concentration determines the type of atrial arrhythmia induced in a porcine model of acute alcoholic intoxication.

    PubMed

    Anadon, M J; Almendral, J; González, P; Zaballos, M; Delcan, J L; De Guevara, J L

    1996-11-01

    Alcohol abuse has long been suspected clinically to cause paroxysmal atrial tachyarrhythmias. However, such a relationship has never been conclusively proven, partly due to the lack of experimental evidence. Although atrial fibrillation (AF) is the most common atrial arrhythmia attributed to acute alcoholic ingestion, atrial flutter has occasionally been noted. We analyzed the possible role of alcohol in initiation and/or maintenance of a variety of atrial tachyarrhythmias in a closed-chest porcine model. Nine pigs underwent nine endocardial right atrial stimulation protocols (RASP) at baseline and 17 RASPs after increasing doses of ethanol (first infusion 1,230 mg/kg, second infusion 870 mg/kg) by means of one multipolar catheter advanced under heavy sedation from the femoral vein. Each RASP included 1, 2, and 3 extrastimuli, and rapid pacing at 5 times diastolic threshold. Venous ethanol concentrations were measured (HPGC method) every 10 minutes and at the time of arrhythmia induction. Atrial tachyarrhythmias were induced in 4 of 9 baseline RASPs, and lasted for a mean of 21 seconds, and in 16 of 17 RASPs after alcohol lasting for a mean of 357 seconds. Only fibrillation was observed at the baseline RASP. The atrial tachyarrhythmias induced after alcohol were AF in 11 RASPs and atrial flutter in 5 RASPs (in 5 animals). The mean venous ethanol concentration at the time of the longest arrhythmia induced for each RASP were 200 +/- 89 mg/dL for RASP inducing fibrillation and 292 +/- 40 mg/dL for RASP inducing flutter (P < 0.05). Flutter tended to be sustained (> 1 minute in duration) more often than fibrillation (4 of 5 flutter vs 2 of 11 fibrillation P < 0.05). In three experiments, atrial flutter persisted for > 10 minutes and was terminated by overdrive atrial pacing. We concluded: (1) in this closed-chest porcine model, an ethanol infusion facilitates a variety of atrial arrhythmias related to the ethanol concentration; (2) flutter tended to be sustained, and its termination by overdrive pacing suggests the possibility of an alcohol induced reentrant mechanism; and (3) the higher concentration required for atrial flutter, exceeding that usually seen in humans, may help to explain the rarity of atrial flutter in clinical alcohol intoxication. PMID:8945078

  2. 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 ...

  3. Acute right ventricular failure in a patient with hepatic cirrhosis.

    PubMed

    Soto Soto, Jose; Geiger, Xochiquetzal; Johnson, Margaret M

    2012-01-01

    Pulmonary embolic disease is most commonly a manifestation of venous thromboembolism (VTE). However, fat, tumor, and air may all embolize to the pulmonary vasculature and lymphatics resulting in various clinical manifestations. Tumor emboli to small pulmonary vessels and lymphatics can lead to hypoxemic respiratory failure and shock. We present a 62-year-old male with history of mild COPD and end-stage liver disease secondary to hepatitis C admitted due to progressive shortness of breath and hypoxemia who developed shock and right ventricular failure. After a negative evaluation for venous thromboembolic disease, he had progressive respiratory and hemodynamic deterioration despite mechanical ventilation, renal replacement therapy, and vasopressive/inotropic support. Postmortem examination revealed diffuse micronodular moderately differentiated hepatocellular carcinoma (HCC) without a discrete mass, as well as numerous HCC tumor emboli to the lung and focally to the heart, consistent with disseminated hepatocellular tumor microembolism. PMID:23316403

  4. Metadoxine improves the three- and six-month survival rates in patients with severe alcoholic hepatitis

    PubMed Central

    Higuera-de la Tijera, Fátima; Servín-Caamaño, Alfredo I; Serralde-Zúñiga, Aurora E; Cruz-Herrera, Javier; Pérez-Torres, Eduardo; Abdo-Francis, Juan M; Salas-Gordillo, Francisco; Pérez-Hernández, José L

    2015-01-01

    AIM: To evaluate the impact of metadoxine (MTD) on the 3- and 6-mo survival of patients with severe alcoholic hepatitis (AH). METHODS: This study was an open-label clinical trial, performed at the “Hospital General de México, Dr. Eduardo Liceaga”. We randomized 135 patients who met the criteria for severe AH into the following groups: 35 patients received prednisone (PDN) 40 mg/d, 35 patients received PDN+MTD 500 mg three times daily, 33 patients received pentoxifylline (PTX) 400 mg three times daily, and 32 patients received PTX+MTD 500 mg three times daily. The duration of the treatment for all of the groups was 30 d. RESULTS: In the groups treated with the MTD, the survival rate was higher at 3 mo (PTX+MTD 59.4% vs PTX 33.3%, P = 0.04; PDN+MTD 68.6% vs PDN 20%, P = 0.0001) and at 6 mo (PTX+MTD 50% vs PTX 18.2%, P = 0.01; PDN+MTD 48.6% vs PDN 20%, P = 0.003) than in the groups not treated with MTD. A relapse in alcohol intake was the primary independent factor predicting mortality at 6 mo. The patients receiving MTD maintained greater abstinence than those who did not receive it (74.5% vs 59.4%, P = 0.02). CONCLUSION: MTD improves the 3- and 6-mo survival rates in patients with severe AH. Alcohol abstinence is a key factor for survival in these patients. The patients who received the combination therapy with MTD were more likely to maintain abstinence than those who received monotherapy with either PDN or PTX. PMID:25945012

  5. Effects of Acute Alcohol Consumption in Older and Younger Adults: Perceived Impairment Versus Psychomotor Performance*

    PubMed Central

    Gilbertson, Rebecca; Ceballos, Natalie A.; Prather, Robert; Nixon, Sara Jo

    2009-01-01

    Objective: Perceived impairment and psychomotor performance following acute alcohol administration in older (ages 50-74, n = 42; 22 male) and younger (ages 25-35, n = 26; 12 male) adults were investigated in this study. Method: Double-blind, placebo-controlled alcohol administration techniques were designed to produce peak levels of breath alcohol concentration consistent with an episode of social drinking (40 mg/100 ml). Behavioral measures (Trail Making Test, Forms A and B), as well as measures of self-reported perceived intoxication and impairment, were administered on the ascending and descending limbs at common time points after beverage ingestion. Results: Results indicated that psychomotor performance differences did not parallel self-reported levels of perceived impairment. Relative to younger adults, older adults exhibited performance deficits on the ascending limb while simultaneously reporting less perceived impairment. Conversely, on the descending limb, older adults who received alcohol reported more perceived impairment than did those who received placebo, although psychomotor performance between these two groups of older drinkers did not differ. For younger participants, a moderate dose of alcohol facilitated performance on the ascending limb; however, these differences were not reflected on the descending limb. Conclusions: These results reinforce the common knowledge that self-reported measures may not provide an accurate reflection of performance outcomes and, importantly, that older adults may be impaired even under a moderate dose of alcohol, although they may not be aware (i.e., report) of this impairment. PMID:19261236

  6. 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 ...

  7. Acute Hepatitis E Infection Accounts for Some Cases of Suspected Drug-Induced Liver Injury

    PubMed Central

    Davern, Timothy J.; Chalasani, Naga; Fontana, Robert J.; Hayashi, Paul H.; Protiva, Petr; Kleiner, David E.; Engle, Ronald E.; Nguyen, Hanh; Emerson, Suzanne U.; Purcell, Robert H.; Tillmann, Hans L.; Gu, Jiezhun; Serrano, Jose; Hoofnagle, Jay H.

    2013-01-01

    Background & Aims The diagnosis of drug-induced liver injury relies upon exclusion of other causes, including viral hepatitis A, B, and C. Hepatitis E virus (HEV) infection has been proposed as another cause of suspected drug-induced liver disease. We assessed the frequency of HEV infection among patients with drug-induced liver injury in the United States. Methods The drug-induced liver injury network (DILIN) is a prospective study of patients with suspected drug-induced liver injury; clinical information and biological samples are collected to investigate pathogenesis and disease progression. We analyzed serum samples, collected from patients enrolled in DILIN, for immunoglobulin (Ig)G and IgM against HEV; selected samples were tested for HEV RNA. Results Among 318 patients with suspected drug-induced liver injury, 50 (16%) tested positive for anti-HEV IgG and 9 (3%) for anti-HEV IgM. The samples that contained anti-HEV IgM (collected 2 to 24 weeks after onset of symptoms) included 4 that tested positive for HEV RNA, genotype 3. Samples from the 6-month follow-up visit were available from 4 patients; they were negative for anti-HEV IgM, but levels of anti-HEV IgG increased with time. Patients that had anti-HEV IgM were mostly from older men (89%; mean age, 67 years) and 2 were HIV positive. Clinical reassessment of the 9 patients with anti-HEV IgM indicated that acute hepatitis E was the most likely diagnosis for 7 and might be the primary diagnosis for 2. Conclusion HEV infection contributes to a small but important proportion of cases of acute liver injury that are suspected of being drug induced. Serologic testing for HEV infection should be performed—particularly if clinical features are compatible with acute viral hepatitis. PMID:21855518

  8. Liver iron is predictive of death in alcoholic cirrhosis: a multivariate study of 229 consecutive patients with alcoholic and/or hepatitis C virus cirrhosis: a prospective follow up study

    PubMed Central

    Ganne-Carrie, N; Christidis, C; Chastang, C; Ziol, M; Chapel, F; Imbert-Bismut, F; Trinchet, J; Guettier, C; Beaugrand, M

    2000-01-01

    BACKGROUND/AIMS—A study was undertaken of liver biopsy samples from 229 consecutive patients with alcoholic or hepatitis C virus related cirrhosis who were prospectively followed until January 1996 to evaluate the influence of liver iron content on survival and the occurrence of hepatocellular carcinoma.?METHODS—Hepatic iron content was measured with a validated semiquantitative score, and its predictive value for survival and the occurrence of hepatocellular carcinoma was assessed.?RESULTS—130 patients had detectable iron at enrolment. During follow up (57 (28) months), 95 patients died and 39 patients developed hepatocellular carcinoma. No significant relation was found between hepatic iron and the occurrence of hepatocellular carcinoma. Conversely, the presence of iron was predictive of death in alcoholic patients (p = 0.007) by the log rank test but not in patients with hepatitis C virus related (p = 0.71) or mixed (p = 0.98) cirrhosis. The predictive value of hepatic iron content in patients with alcoholic cirrhosis was confirmed by the Cox model using either a binary coding (p = 0.009; relative risk = 2.27; 95% confidence interval 1.2 to 4.19) or the continuous values (p = 0.002).?CONCLUSIONS—These results suggest that hepatic iron enhances liver lesions caused by alcohol but not those caused by hepatitis C virus.???Keywords: cirrhosis; liver; iron; survival; hepatocellular carcinoma; alcohol PMID:10644325

  9. Two sides of one coin: massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure

    PubMed Central

    Weng, Hong-Lei; Cai, Xiaobo; Yuan, Xiaodong; Liebe, Roman; Dooley, Steven; Li, Hai; Wang, Tai-Ling

    2015-01-01

    Massive hepatic necrosis is a key event underlying acute liver failure, a serious clinical syndrome with high mortality. Massive hepatic necrosis in acute liver failure has unique pathophysiological characteristics including extremely rapid parenchymal cell death and removal. On the other hand, massive necrosis rapidly induces the activation of liver progenitor cells, the so-called “second pathway of liver regeneration.” The final clinical outcome of acute liver failure depends on whether liver progenitor cell-mediated regeneration can efficiently restore parenchymal mass and function within a short time. This review summarizes the current knowledge regarding massive hepatic necrosis and liver progenitor cell-mediated regeneration in patients with acute liver failure, the two sides of one coin.

  10. Dissociation between diurnal cycles in locomotor activity, feeding behavior and hepatic PERIOD2 expression in chronic alcohol-fed mice.

    PubMed

    Zhou, Peng; Werner, John H; Lee, Donghoon; Sheppard, Aaron D; Liangpunsakul, Suthat; Duffield, Giles E

    2015-06-01

    Chronic alcohol consumption contributes to fatty liver disease. Our studies revealed that the hepatic circadian clock is disturbed in alcohol-induced hepatic steatosis, and effects of chronic alcohol administration upon the clock itself may contribute to steatosis. We extended these findings to explore the effects of chronic alcohol treatment on daily feeding and locomotor activity patterns. Mice were chronically pair-fed ad libitum for 4 weeks using the Lieber-DeCarli liquid diet, with calorie-controlled liquid and standard chow diets as control groups. Locomotor activity, feeding activity, and real-time bioluminescence recording of PERIOD2::LUCIFERASE expression in tissue explants were measured. Mice on liquid control and chow diets exhibited normal profiles of locomotor activity, with a ratio of 22:78% day/night activity and a peak during early night. This pattern was dramatically altered in alcohol-fed mice, marked by a 49:51% ratio and the absence of a distinct peak. While chow-diet fed mice had a normal 24:76% ratio of feeding activity, with a peak in the early night, this pattern was dramatically altered in both liquid-diet groups: mice had a 43:57% ratio, and an absence of a distinct peak. Temporal differences were also observed between the two liquid-diet groups during late day. Cosinor analysis revealed a ?4-h and ?6-h shift in the alcohol-fed group feeding and locomotor activity rhythms, respectively. Analysis of hepatic PER2 expression revealed that the molecular clock in alcohol-fed and control liquid-diet mice was shifted by ?11 h and ?6 h, respectively. No differences were observed in suprachiasmatic nucleus explants, suggesting that changes in circadian phase in the liver were generated independently from the central clock. These results suggest that chronic alcohol consumption and a liquid diet can differentially modulate the daily rhythmicity of locomotor and feeding behaviors, aspects that might contribute to disturbances in the circadian timing system and development of hepatic steatosis. PMID:25960184

  11. Alcohol-impaired speed and accuracy of cognitive functions: a review of acute tolerance and recovery of cognitive performance.

    PubMed

    Schweizer, Tom A; Vogel-Sprott, Muriel

    2008-06-01

    Much research on the effects of a dose of alcohol has shown that motor skills recover from impairment as blood alcohol concentrations (BACs) decline and that acute tolerance to alcohol impairment can develop during the course of the dose. Comparable alcohol research on cognitive performance is sparse but has increased with the development of computerized cognitive tasks. This article reviews the results of recent research using these tasks to test the development of acute tolerance in cognitive performance and recovery from impairment during declining BACs. Results show that speed and accuracy do not necessarily agree in detecting cognitive impairment, and this mismatch most frequently occurs during declining BACs. Speed of cognitive performance usually recovers from impairment to drug-free levels during declining BACs, whereas alcohol-increased errors fail to diminish. As a consequence, speed of cognitive processing tends to develop acute tolerance, but no such tendency is shown in accuracy. This "acute protracted error" phenomenon has not previously been documented. The findings pose a challenge to the theory of alcohol tolerance on the basis of physiological adaptation and raise new research questions concerning the independence of speed and accuracy of cognitive processes, as well as hemispheric lateralization of alcohol effects. The occurrence of alcohol-induced protracted cognitive errors long after speed returned to normal is identified as a potential threat to the safety of social drinkers that requires urgent investigation. PMID:18540784

  12. Identification of potential biomarkers of hepatitis B-induced acute liver failure using hepatic cells derived from human skin precursors.

    PubMed

    Rodrigues, Robim M; Sachinidis, Agapios; De Boe, Veerle; Rogiers, Vera; Vanhaecke, Tamara; De Kock, Joery

    2015-09-01

    Besides their role in the elucidation of pathogenic processes of medical and pharmacological nature, biomarkers can also be used to document specific toxicological events. Hepatic cells generated from human skin-derived precursors (hSKP-HPC) were previously shown to be a promising in vitro tool for the evaluation of drug-induced hepatotoxicity. In this study, their capacity to identify potential liver-specific biomarkers at the gene expression level was investigated with particular emphasis on acute liver failure (ALF). To this end, a set of potential ALF-specific biomarkers was established using clinically relevant liver samples obtained from patients suffering from hepatitis B-associated ALF. Subsequently, this data was compared to data obtained from primary human hepatocyte cultures and hSKP-HPC, both exposed to the ALF-inducing reference compound acetaminophen. It was found that both in vitro systems revealed a set of molecules that was previously identified in the ALF liver samples. Yet, only a limited number of molecules was common between both in vitro systems and the ALF liver samples. Each of the in vitro systems could be used independently to identify potential toxicity biomarkers related to ALF. It seems therefore more appropriate to combine primary human hepatocyte cultures with complementary in vitro models to efficiently screen out potential hepatotoxic compounds. PMID:25458485

  13. Acute Hepatic Insulin Resistance Contributes to Hyperglycemia in Rats Following Myocardial Infarction.

    PubMed

    Wang, Jiali; Liu, Baoshan; Han, Hui; Yuan, Qiuhuan; Xue, Mengyang; Xu, Feng; Chen, Yuguo

    2015-01-01

    Although hyperglycemia is common in patients with acute myocardial infarction (MI), the underlying mechanisms are largely unknown. Insulin signaling plays a key role in the regulation of glucose homeostasis. In this study, we test the hypothesis that rapid alteration of insulin signaling pathways could be a potential contributor to acute hyperglycemia after MI. Male rats were used to produce MI by ligation of the left anterior descending coronary artery. Plasma glucose and insulin levels were significantly higher in MI rats than those in controls. Insulin-stimulated tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) was reduced significantly in the liver tissue of MI rats compared with controls, followed by decreased attachment of phosphatidylinositol 3-kinase (PI3K) p85 subunit with IRS1 and Akt phosphorylation. However, insulin-stimulated signaling was not altered significantly in skeletal muscle after MI. The relative mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and G6Pase were slightly higher in the liver tissue of MI rats than those in controls. Rosiglitazone (ROSI) markedly restored hepatic insulin signaling, inhibited gluconeogenesis and reduced plasma glucose levels in MI rats. Insulin resistance develops rapidly in liver but not skeletal muscle after MI, which contributes to acute hyperglycemia. Therapy aimed at potentiating hepatic insulin signaling may be beneficial for MI-induced hyperglycemia. PMID:25730774

  14. Acute Hepatic Insulin Resistance Contributes to Hyperglycemia in Rats Following Myocardial Infarction

    PubMed Central

    Wang, Jiali; Liu, Baoshan; Han, Hui; Yuan, Qiuhuan; Xue, Mengyang; Xu, Feng; Chen, Yuguo

    2015-01-01

    Although hyperglycemia is common in patients with acute myocardial infarction (MI), the underlying mechanisms are largely unknown. Insulin signaling plays a key role in the regulation of glucose homeostasis. In this study, we test the hypothesis that rapid alteration of insulin signaling pathways could be a potential contributor to acute hyperglycemia after MI. Male rats were used to produce MI by ligation of the left anterior descending coronary artery. Plasma glucose and insulin levels were significantly higher in MI rats than those in controls. Insulin-stimulated tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) was reduced significantly in the liver tissue of MI rats compared with controls, followed by decreased attachment of phosphatidylinositol 3-kinase (PI3K) p85 subunit with IRS1 and Akt phosphorylation. However, insulin-stimulated signaling was not altered significantly in skeletal muscle after MI. The relative mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and G6Pase were slightly higher in the liver tissue of MI rats than those in controls. Rosiglitazone (ROSI) markedly restored hepatic insulin signaling, inhibited gluconeogenesis and reduced plasma glucose levels in MI rats. Insulin resistance develops rapidly in liver but not skeletal muscle after MI, which contributes to acute hyperglycemia. Therapy aimed at potentiating hepatic insulin signaling may be beneficial for MI-induced hyperglycemia. PMID:25730774

  15. Acute Effects of Alcohol on Inhibitory Control and Simulated Driving in DUI Offenders

    PubMed Central

    Van Dyke, Nicholas; Fillmore, Mark T.

    2014-01-01

    Introduction The public health costs associated with alcohol-related traffic accidents have prompted considerable research aimed at identifying characteristics of individuals who drive under the influence (DUI) in order to improve treatment and prevention strategies. Survey studies consistently show that DUI offenders self-report higher levels of impulsivity compared to their nonoffending counterparts. However, little is known about how individuals with a DUI history respond under alcohol. Inhibitory control is a behavioral component of impulsivity thought to underlie risky drinking and driving behaviors. Method The present study examined the degree to which DUI drivers display deficits of inhibitory control in response to alcohol and the degree to which alcohol impaired their simulated driving performance. It was hypothesized that DUI offenders would display an increased sensitivity to the acute impairing effects of alcohol on simulated driving performance. Young adult drivers with a history of DUI and a demographically-comparable group of drivers with no history of DUI (controls) were tested following a 0.65 g/kg dose of alcohol and a placebo. Inhibitory control was measured using a cued go/no-go task. Drivers then completed a driving simulation task that yielded multiple indicators of driving performance, such as within-lane deviation, steering rate, centerline crossings and road edge excursions, and drive speed. Results Results showed that although DUI offenders self-reported greater levels of impulsivity than did controls, no group differences were observed in the degree to which alcohol impaired inhibitory control and driving performance. The findings point to the need to identify other aspects of behavioral dysfunction underlying the self-reported impulsivity among DUI offenders, and to better understand the specific driving situations that might pose greater risk to DUI offenders. PMID:24913486

  16. Dietary saturated fatty acids reduce hepatic lipid accumulation but induce fibrotic change in alcohol-fed rats

    PubMed Central

    Chen, Ya-Ling; Peng, Hsiang-Chi; Wang, Xiang-Dong

    2015-01-01

    Background In this study, we evaluated the influence of an ethanol-containing diet with high saturated fatty acids (SFAs) on alcoholic liver disease (ALD) in rats. Methods Male Wistar rats weighing about 160 g were divided into four groups: an ethanol (E) group fed an ethanol-containing liquid diet with 36% total calories as fat (corn oil, olive oil and safflower oil); a control (C) group pair-fed an isoenergetic diet without ethanol; an ethanol with saturated fat (EHS) group fed an ethanol-containing diet which contained 40% total calories as fat (90% lard); and a control with saturated fat (CHS) group fed an isoenergetic diet without ethanol, which contained 40% total calories as fat. Results After 8 weeks of treatment, the liver weight and plasma aspartate aminotransferase (AST) activities in E and EHS groups were significantly higher than those of C group. Significantly higher scores of inflammation, necrosis, and fatty changes were found in E group, whereas significantly higher scores of necrosis, bile duct hyperplasia, and fibrosis were found in EHS group. Although significantly lower plasma adiponectin concentrations were observed in both E and EHS groups, compared to C group, plasma adiponectin in EHS group was significantly higher than that in E group. There was no change in hepatic peroxisome proliferator activated receptor (PPAR)-? expression between E and C groups, and rats in EHS group showed a significantly elevated level compared to the other groups. A lower hepatic sirtuins (SIRT)-1 level was found in E group, but it did not reach statistical significance. Moreover, the highest plasma TGF-?1 level was found in EHS group. Compared to C group, the hepatic reduced glutathione/oxidized glutathione ratio and thiobarbituric acid (TBA)-reactive substance level were significantly increased in E and EHS groups; however, there was no significant difference between E and EHS groups. Significantly increased hepatic CYP2E1 expression was observed in both E and EHS groups, while at the same time, hepatic CYP2E1 in EHS group was the highest among all groups. The hepatic tumor necrosis factor (TNF)-?, interleukin (IL)-1?, IL-6, and IL-10 concentrations in the E group were significantly higher than those in C group, whereas the hepatic IL-6 and IL-10 concentrations in ES group were significantly lower than those of E group. Conclusions These results suggested that dietary saturated fats may inhibit hepatic fat accumulation and induce hepatic fibrosis in rats under chronic alcohol intake.

  17. Novel Management of Acute or Secondary Biliary Liver Conditions Using Hepatically Differentiated Human Dental Pulp Cells

    PubMed Central

    Ishkitiev, Nikolay; Imai, Toshio; Tanaka, Tomoko; Fushimi, Naho; Mitev, Vanyo; Okada, Mio; Tominaga, Noriko; Ono, Sachie; Ishikawa, Hiroshi

    2015-01-01

    The current definitive treatment for acute or chronic liver condition, that is, cirrhosis, is liver transplantation from a limited number of donors, which might cause complications after donation. Hence, bone marrow stem cell transplantation has been developed, but the risk of carcinogenesis remains. We have recently developed a protocol for hepatic differentiation of CD117+ stem cells from human exfoliated deciduous teeth (SHED). In the present study, we examine whether SHED hepatically differentiated (hd) in vitro could be used to treat acute liver injury (ALI) and secondary biliary cirrhosis. The CD117+ cell fraction was magnetically separated from SHED and then differentiated into hepatocyte-like cells in vitro. The cells were transplanted into rats with either ALI or induced secondary biliary cirrhosis. Engraftment of human liver cells was determined immunohistochemically and by in situ hybridization. Recovery of liver function was examined by means of histochemical and serological tests. Livers of transplanted animals were strongly positive for human immunohistochemical factors, and in situ hybridization confirmed engraftment of human hepatocytes. The tests for recovery of liver function confirmed the presence of human hepatic markers in the animals' blood serum and lack of fibrosis and functional integration of transplanted human cells into livers. No evidence of malignancy was found. We show that in vitro hdSHED engraft morphologically and functionally into the livers of rats having acute injury or secondary biliary cirrhosis. SHED are readily accessible adult stem cells, capable of proliferating in large numbers before differentiating in vitro. This makes SHED an appropriate and safe stem cell source for regenerative medicine. PMID:25234861

  18. Epigenetic signatures of alcohol abuse and hepatitis infection during human hepatocarcinogenesis

    PubMed Central

    Hlady, Ryan A.; Tiedemann, Rochelle L.; Puszyk, William; Zendejas, Ivan; Roberts, Lewis R.; Choi, Jeong-Hyeon; Liu, Chen; Robertson, Keith D.

    2014-01-01

    Hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide. Deregulated DNA methylation landscapes are ubiquitous in human cancers. Interpretation of epigenetic aberrations in HCC is confounded by multiple etiologic drivers and underlying cirrhosis. We globally profiled the DNA methylome of 34 normal and 122 liver disease tissues arising in settings of hepatitis B (HBV) or C (HCV) viral infection, alcoholism (EtOH), and other causes to examine how these environmental agents impact DNA methylation in a manner that contributes to liver disease. Our results demonstrate that each ‘exposure’ leaves unique and overlapping signatures on the methylome. CpGs aberrantly methylated in cirrhosis-HCV and conserved in HCC were enriched for cancer driver genes, suggesting a pathogenic role for HCV-induced methylation changes. Additionally, large genomic regions displaying stepwise hypermethylation or hypomethylation during disease progression were identified. HCC-HCV/EtOH methylomes overlap highly with cryptogenic HCC, suggesting shared epigenetically deregulated pathways for hepatocarcinogenesis. Finally, overlapping methylation abnormalities between primary and cultured tumors unveil conserved epigenetic signatures in HCC. Taken together, this study reveals profound epigenome deregulation in HCC beginning during cirrhosis and influenced by common environmental agents. These results lay the foundation for defining epigenetic drivers and clinically useful methylation markers for HCC. PMID:25294808

  19. Imatinib-induced Severe Hepatitis in a 9-Year-old Girl With Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia.

    PubMed

    Suzuki, Ryoko; Kobayashi, Chie; Sakai, Aiko; Fukushima, Hiroko; Tagawa, Manabu; Satomi, Kaishi; Nanmoku, Toru; Sumazaki, Ryo; Fukushima, Takashi

    2015-08-01

    Imatinib mesylate has dramatically improved the outcome of children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph ALL) and is now included as first-line therapy. Uncommon adverse effects of this drug for pediatric use, however, are largely unknown. We report the first case of a 9-year-old child who developed severe acute hepatitis with grade 4 transaminases and bilirubin elevation during imatinib treatment for Ph ALL. Liver biopsy showed extensive lobular and pericentral necrosis of hepatocytes. Liver function recovered after discontinuing imatinib with a 4-week prednisolone. Extensive hepatic necrosis should be considered not only in adults but also in children under imatinib administration. PMID:25929609

  20. Acute myocardial infarction induced by concurrent use of adderall and alcohol in an adolescent.

    PubMed

    Sharma, Jayendra; de Castro, Carlyle; Chatterjee, Partha; Pinto, Rohit

    2013-01-01

    Adderall (amphetamine, dextroamphetamine mixed salts), a widely prescribed stimulant for the treatment of attention-deficit/hyperactivity disorder in children and adolescents, is considered safe with due precautions. Nonmedical use of Adderall is prevalent and rising in high school and college students. Use of prescribed Adderall without intention to overdose as a cause of myocardial infarction is extremely rare, and to our knowledge, only 3 cases have been reported in the pediatric literature. We report a case of acute myocardial infarction in an adolescent without cardiovascular risk factors who took the total prescribed daily dose of Adderall one time while consuming alcohol. The sporadic use of Adderall with alcohol creates a potentially dangerous situation with serious cardiovascular adverse effects. We should have a high degree of suspicion for children and adolescents on stimulant therapy who present with chest pain and an abnormal electrocardiogram in the pediatric emergency department, and there is a need to evaluate them for myocardial ischemia and infarction. PMID:23283274

  1. A case of acute hepatitis C caused by interspousal transmission after 30 years of marriage.

    PubMed

    Nishimura, Naoyuki; Isoda, Norio; Higashizawa, Toshihiko; Otake, Toshiya; Tsukui, Mamiko; Nagashima, Shigeo; Takahashi, Masaharu; Okamoto, Hiroaki; Sugano, Kentaro

    2010-02-01

    We describe a case of interspousal transmission of hepatitis C virus (HCV) infection after 30 years of marriage which was confirmed by gene analysis. A 60-year-old man was referred to our hospital because of severe hepatic dysfunction. Laboratory findings showed that HCV-Ab titer and qualitative Amplicor HCV were both positive in low levels. Because the patient regularly consumes various health foods, it was initially difficult to rule out drug-induced hepatopathy, but the patient was diagnosed with acute hepatitis C when HCV antibody titer increased 4 months later. Because his wife also tested positive for HCV antibody, interspousal transmission was suspected, and gene analysis was performed. Both husband and wife had HCV 1b, and the base sequence homology of 1087 base pairs (bp) in the NS5B region was 98.6% (99.4% at the amino acid level). In addition, upon analysis of the E1 and E2 junctional region sequence (268 bp) including hypervariable region 1 (HVR-1), a close relationship (89.2-99.6%) between clones obtained from each spouse was observed, thus confirming that the source of infection was his wife. Thorough medical history taking suggested that sexual intercourse was the most likely route of infection. In previous large-scale clinical studies, the frequency of HCV infection between married couples has been extremely low, but it is important to obtain informed consent regarding the potential risk of infection. PMID:26189908

  2. The Protective Effect of Resveratrol on Concanavalin-A-Induced Acute Hepatic Injury in Mice

    PubMed Central

    Zhou, Yingqun; Chen, Kan; He, Lei; Xia, Yujing; Dai, Weiqi; Wang, Fan; Li, Jingjing; Li, Sainan; Liu, Tong; Wang, Jianrong; Lu, Wenxia; Yin, Qin; Zhou, Yuqing; Lu, Jie; Teng, Hongfei; Guo, Chuanyong

    2015-01-01

    Pharmacologic Relevance. Resveratrol, an antioxidant derived from grapes, has been reported to modulate the inflammatory process. In this study, we investigated the effects of resveratrol and its mechanism of protection on concanavalin-A- (ConA-) induced liver injury in mice. Materials and Methods. Acute autoimmune hepatitis was induced by ConA (20?mg/kg) in Balb/C mice; mice were treated with resveratrol (10, 20, and 30?mg/kg) daily by oral gavage for fourteen days prior to a single intravenous injection of ConA. Eight hours after injection, histologic grading, proinflammatory cytokine levels, and hedgehog pathway activity were determined. Results. After ConA injection, the cytokines IL-2, IL-6, and TNF-? were increased, and Sonic hedgehog (Shh), Glioblastoma- (Gli-) 1, and Patched (Ptc) levels significantly increased. Pretreatment with resveratrol ameliorated the pathologic effects of ConA-induced autoimmune hepatitis and significantly inhibited IL-2, IL-6, TNF-?, Shh, Gli-1, and Ptc. The effects of resveratrol on the hedgehog pathway were studied by western blotting and immunohistochemistry. Resveratrol decreased Shh expression, possibly by inhibiting Shh expression in order to reduce Gli-1 and Ptc expression. Conclusion. Resveratrol protects against ConA-induced autoimmune hepatitis by decreasing cytokines expression in mice. The decreases seen in Gli-1 and Ptc may correlate with the amelioration of hedgehog pathway activity. PMID:26089871

  3. Heterotopic auxiliary rat liver transplantation with flow-regulated portal vein arterialization in acute hepatic failure.

    PubMed

    Schleimer, Karina; Kalder, Johannes; Grommes, Jochen; Jalaie, Houman; Tawadros, Samir; Greiner, Andreas; Jacobs, Michael; Kokozidou, Maria

    2014-01-01

    In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the failing native liver has regenerated.(1-3) The APOLT-method, the orthotopic implantation of auxiliary segments- averts most of the technical problems. However this method necessitates extensive resections of both the native liver and the graft.(4) In 1998, Erhard developed the heterotopic auxiliary liver transplantation (HALT) utilizing portal vein arterialization (PVA) (Figure 1). This technique showed promising initial clinical results.(5-6) We developed a HALT-technique with flow-regulated PVA in the rat to examine the influence of flow-regulated PVA on graft morphology and function (Figure 2). A liver graft reduced to 30 % of its original size, was heterotopically implanted in the right renal region of the recipient after explantation of the right kidney.  The infra-hepatic caval vein of the graft was anastomosed with the infrahepatic caval vein of the recipient. The arterialization of the donor's portal vein was carried out via the recipient's right renal artery with the stent technique. The blood-flow regulation of the arterialized portal vein was achieved with the use of a stent with an internal diameter of 0.3 mm. The celiac trunk of the graft was end-to-side anastomosed with the recipient's aorta and the bile duct was implanted into the duodenum. A subtotal resection of the native liver was performed to induce acute hepatic failure. (7) In this manner 112 transplantations were performed. The perioperative survival rate was 90% and the 6-week survival rate was 80%. Six weeks after operation, the native liver regenerated, showing an increase in weight from 2.3±0.8 g to 9.8±1 g. At this time, the graft's weight decreased from 3.3±0.8 g to 2.3±0.8 g. We were able to obtain promising long-term results in terms of graft morphology and function. HALT with flow-regulated PVA reliably bridges acute hepatic failure until the native liver regenerates. PMID:25285729

  4. 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, ...

  5. Hepatic Crown-Like Structure: A Unique Histological Feature in Non-Alcoholic Steatohepatitis in Mice and Humans

    PubMed Central

    Suganami, Takayoshi; Konuma, Kuniha; Marumoto, Yoshio; Terai, Shuji; Sakugawa, Hiroshi; Kanai, Sayaka; Hamaguchi, Miho; Fukaishi, Takahiro; Aoe, Seiichiro; Akiyoshi, Kazunari; Komohara, Yoshihiro; Takeya, Motohiro; Sakaida, Isao; Ogawa, Yoshihiro

    2013-01-01

    Although macrophages are thought to be crucial for the pathogenesis of chronic inflammatory diseases, how they are involved in disease progression from simple steatosis to non-alcoholic steatohepatitis (NASH) is poorly understood. Here we report the unique histological structure termed “hepatic crown-like structures (hCLS)” in the mouse model of human NASH; melanocortin-4 receptor deficient mice fed a Western diet. In hCLS, CD11c-positive macrophages aggregate to surround hepatocytes with large lipid droplets, which is similar to those described in obese adipose tissue. Histological analysis revealed that hCLS is closely associated with activated fibroblasts and collagen deposition. When treatment with clodronate liposomes effectively depletes macrophages scattered in the liver, with those in hCLS intact, hepatic expression of inflammatory and fibrogenic genes is unaffected, suggesting that hCLS is an important source of inflammation and fibrosis during the progression of NASH. Notably, the number of hCLS is positively correlated with the extent of liver fibrosis. We also observed increased number of hCLS in the liver of non-alcoholic fatty liver disease/NASH patients. Collectively, our data provide evidence that hCLS is involved in the development of hepatic inflammation and fibrosis, thereby suggesting its pathophysiologic role in disease progression from simple steatosis to NASH. PMID:24349208

  6. Endovascular Treatment of Acute Arterial Hemorrhage in Trauma Patients Using Ethylene Vinyl Alcohol Copolymer (Onyx)

    Microsoft Academic Search

    R. Müller-Wille; P. Heiss; T. Herold; E. M. Jung; A. G. Schreyer; O. W. Hamer; J. Rennert; P. Hoffstetter; C. Stroszczynski; N. Zorger

    Purpose  This study was designed to determine the feasibility and efficacy of endovascular embolization with liquid embolic agent ethylene\\u000a vinyl alcohol copolymer (Onyx) in patients with acute traumatic arterial bleeding.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  This is a retrospective review of 13 patients (9 men and 4 women; mean age 45 years) with severe trauma who underwent embolotherapy\\u000a using Onyx from November 2003 to February 2009. Bleeding

  7. Alcoholism

    Microsoft Academic Search

    James C. Garbutt

    The use of alcohol is woven into our culture in a most complex fashion. The majority of adults in the United States consume\\u000a alcohol, yet alcohol also causes nearly 75,000 deaths per year and costs our society on the order of 150 billion per year.\\u000a Harm from alcohol can occur in a number of ways. First, if alcohol is consumed

  8. Hepatic mitochondrial DNA depletion after an alcohol binge in mice: probable role of peroxynitrite and modulation by manganese superoxide dismutase.

    PubMed

    Larosche, Isabelle; Lettéron, Philippe; Berson, Alain; Fromenty, Bernard; Huang, Ting-Ting; Moreau, Richard; Pessayre, Dominique; Mansouri, Abdellah

    2010-03-01

    Alcohol consumption increases reactive oxygen species (ROS) formation, which can damage mitochondrial DNA (mtDNA) and alter mitochondrial function. To test whether manganese superoxide dismutase (MnSOD) modulates acute alcohol-induced mitochondrial alterations, transgenic MnSOD-overexpressing (MnSOD(+++)) mice, heterozygous knockout (MnSOD(+/-)) mice, and wild-type (WT) littermates were sacrificed 2 or 24 h after intragastric ethanol administration (5 g/kg). Alcohol administration further increased MnSOD activity in MnSOD(+++) mice, but further decreased it in MnSOD(+/-) mice. In WT mice, alcohol administration transiently increased mitochondrial ROS formation, decreased mitochondrial glutathione, depleted and damaged mtDNA, and decreased complex I and V activities; alcohol durably increased inducible nitric-oxide synthase (NOS) expression, plasma nitrites/nitrates, and the nitration of tyrosine residues in complex V proteins. These effects were prevented in MnSOD(+++) mice and prolonged in MnSOD(+/-) mice. In alcoholized WT or MnSOD(+/-) mice, mtDNA depletion and the nitration of tyrosine residues in complex I and V proteins were prevented or attenuated by cotreatment with tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), a superoxide scavenger; N(omega)-nitro-l-arginine methyl ester and N-[3-(aminomethyl)benzyl]acetamidine (1,400W), two NOS inhibitors; or uric acid, a peroxynitrite scavenger. In conclusion, MnSOD overexpression prevents, and MnSOD deficiency prolongs, mtDNA depletion after an acute alcohol binge in mice. The protective effects of MnSOD, tempol, NOS inhibitors, and uric acid point out a role of the superoxide anion reacting with NO to form mtDNA-damaging peroxynitrite. PMID:20016022

  9. PD1 Expression in Acute Hepatitis C Virus (HCV) Infection Is Associated with HCV-Specific CD8 Exhaustion

    Microsoft Academic Search

    Simona Urbani; Barbara Amadei; Daniela Tola; Marco Massari; Simona Schivazappa; Gabriele Missale; Carlo Ferrari

    2006-01-01

    Hepatitis C virus (HCV)-specific CD8 cell exhaustion may represent a mechanism of HCV persistence. The inhibitory receptor PD-1 has been reported to be up-regulated in exhausted CD8 cells. Therefore, we studied PD-1 expression longitudinally during acute HCV infection. Most HCV-specific CD8 cells expressed PD-1 at the time of acute illness, irrespective of the final outcome. PD-1 expression declined with the

  10. Primary hepatic circumscribed Burkitt's lymphoma that developed after acute hepatitis B: report of a case with a review of the literature.

    PubMed

    Sekiguchi, Yasunobu; Yoshikawa, Hitomi; Shimada, Asami; Imai, Hidenori; Wakabayashi, Mutsumi; Sugimoto, Keiji; Nakamura, Noriko; Sawada, Tomohiro; Takeuchi, Kengo; Ohta, Yasunori; Komatsu, Norio; Noguchi, Masaaki

    2013-01-01

    A Japanese man aged 30 years old contracted acute hepatitis B in October 2011, and was cured following conservative treatment. Mild hepatosplenomegaly was the only positive finding on computed tomography (CT) and ultrasonography at that time. In May 2012, slight impairment of the liver function was detected again in the patient; an abdominal CT at this time revealed a tumor mass in the right hepatic lobe, so subsegmentectomy of the right hepatic lobe was performed. On the basis of the findings of the resected specimen, primary hepatic circumscribed Burkitt's lymphoma (sporadic form), stage IA, was diagnosed. Multiple cycles of hyper-CVAD/MTX-Ara-C therapy with concomitant rituximab were administered, under which the patient was successfully maintained in complete remission. To date, at least 15 cases of primary hepatic Burkitt's lymphoma have been reported in the literature; all of the 11 patients without concurrent human immunodeficiency virus (HIV) infection had the sporadic form of the disease. Asians were relatively common (7 patients) among these patients, and patients in their childhood or adolescence accounted for a considerable proportion. Therefore, the present case may be regarded as rather typical. The presence of hepatitis virus infection as a background disorder other than HIV is considered to be of profound interest etiologically. PMID:23995115

  11. Acute intermittent porphyria causes hepatic mitochondrial energetic failure in a mouse model.

    PubMed

    Homedan, Chadi; Laafi, Jihane; Schmitt, Caroline; Gueguen, Naïg; Lefebvre, Thibaud; Karim, Zoubida; Desquiret-Dumas, Valérie; Wetterwald, Céline; Deybach, Jean-Charles; Gouya, Laurent; Puy, Hervé; Reynier, Pascal; Malthièry, Yves

    2014-06-01

    Acute intermittent porphyria (AIP), an inherited hepatic disorder, is due to a defect of hydroxymethylbilane synthase (HMBS), an enzyme involved in heme biosynthesis. AIP is characterized by recurrent, life-threatening attacks at least partly due to the increased hepatic production of 5-aminolaevulinic acid (ALA). Both the mitochondrial enzyme, ALA synthase (ALAS) 1, involved in the first step of heme biosynthesis, which is closely linked to mitochondrial bioenergetic pathways, and the promise of an ALAS1 siRNA hepatic therapy in humans, led us to investigate hepatic energetic metabolism in Hmbs KO mice treated with phenobarbital. The mitochondrial respiratory chain (RC) and the tricarboxylic acid (TCA) cycle were explored in the Hmbs(-/-) mouse model. RC and TCA cycle were significantly affected in comparison to controls in mice treated with phenobarbital with decreased activities of RC complexes I (-52%, (**)p<0.01), II (-50%, (**)p<0.01) and III (-55%, (*)p<0.05), and decreased activity of ?-ketoglutarate dehydrogenase (-64%, (*)p<0.05), citrate synthase (-48%, (**)p<0.01) and succinate dehydrogenase (-53%, (*)p<0.05). Complex II-driven succinate respiration was also significantly affected. Most of these metabolic alterations were at least partially restored after the phenobarbital arrest and heme arginate administration. These results suggest a cataplerosis of the TCA cycle induced by phenobarbital, caused by the massive withdrawal of succinyl-CoA by ALAS induction, such that the TCA cycle is unable to supply the reduced cofactors to the RC. This profound and reversible impact of AIP on mitochondrial energetic metabolism offers new insights into the beneficial effect of heme, glucose and ALAS1 siRNA treatments by limiting the cataplerosis of TCA cycle. PMID:24727425

  12. 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 ...

  13. Adaptation of hepatic mitochondrial function in humans with non-alcoholic Fatty liver is lost in steatohepatitis.

    PubMed

    Koliaki, Chrysi; Szendroedi, Julia; Kaul, Kirti; Jelenik, Tomas; Nowotny, Peter; Jankowiak, Frank; Herder, Christian; Carstensen, Maren; Krausch, Markus; Knoefel, Wolfram Trudo; Schlensak, Matthias; Roden, Michael

    2015-05-01

    The association of hepatic mitochondrial function with insulin resistance and non-alcoholic fatty liver (NAFL) or steatohepatitis (NASH) remains unclear. This study applied high-resolution respirometry to directly quantify mitochondrial respiration in liver biopsies of obese insulin-resistant humans without (n = 18) or with (n = 16) histologically proven NAFL or with NASH (n = 7) compared to lean individuals (n = 12). Despite similar mitochondrial content, obese humans with or without NAFL had 4.3- to 5.0-fold higher maximal respiration rates in isolated mitochondria than lean persons. NASH patients featured higher mitochondrial mass, but 31%-40% lower maximal respiration, which associated with greater hepatic insulin resistance, mitochondrial uncoupling, and leaking activity. In NASH, augmented hepatic oxidative stress (H2O2, lipid peroxides) and oxidative DNA damage (8-OH-deoxyguanosine) was paralleled by reduced anti-oxidant defense capacity and increased inflammatory response. These data suggest adaptation of the liver ("hepatic mitochondrial flexibility") at early stages of obesity-related insulin resistance, which is subsequently lost in NASH. PMID:25955209

  14. Use of Nucleoside (Tide) Analogues in Patients with Hepatitis B-Related Acute Liver Failure

    PubMed Central

    Dao, Doan Y; Seremba, Emmanuel; Ajmera, Veeral; Sanders, Corron; Hynan, Linda S.; Lee, William M.

    2013-01-01

    Background & Aims The efficacy of nucleoside(tide) analogues (NA) in the treatment of acute liver failure due to hepatitis B virus (HBV-ALF) remains controversial. We determined retrospectively the impact of NAs in a large cohort of patients with HBV-ALF. Methods The US Acute Liver Failure Study Group, a 23-site registry prospectively enrolled 1,413 patients with ALF with different etiologies between 1998 and 2008. Of those, 105 patients were identified as HBV-ALF patients, of whom we excluded those without data on NA use or with co-infection with hepatitis C, leaving 85 patients, 43 of whom had received NA treatment. HBV-DNA on admission was quantified by real time polymerase chain reaction. Results The treated and untreated groups were similar in most respects but differed significantly in regard to higher aminotransferase and bilirubin levels and hepatic coma grades, all being observed in the untreated group. Median duration of NA treatment was 6 (range: 1-21) days. Overall survival in the NA treated and untreated groups were 61% and 64% respectively (p=0.72). Rates of transplant-free survival were 21% and 36% in the treated and untreated groups respectively, p=0.42. Multivariate analysis revealed that not using a NA [odds ratio (OR) 4.4, 95% CI 1.1-18.1, p=0.041], hepatic coma grade I or II [OR 14.4, 95% CI 3.3-62.8, p<0.001], prolonged prothrombin time (PT) [OR 0.59, 95% CI 0.39-0.89, p=0.012] were predictors of improved transplant-free survival. Conclusions Patients who are admitted with established HBV-ALF do not appear to benefit from viral suppression using nucleoside(tide) analogues presumably because of rapid disease evolution and short treatment duration. Despite the lack of benefit, NAs should still be given to transplantation candidates since viral suppression prevents recurrence after grafting. PMID:22198704

  15. Acute hepatitis C infection in HIV positive men who have sex with men in Paris, France, 2001-2004.

    PubMed

    Gambotti, L; Batisse, D; Colin-de-Verdiere, N; Delaroque-Astagneau, E; Desenclos, J C; Dominguez, S; Dupont, C; Duval, X; Gervais, A; Ghosn, J; Larsen, C; Pol, S; Serpaggi, J; Simon, A; Valantin, M A; Velter, A

    2005-05-01

    In mid-2004, three Parisian hospital wards informed the Institut de veille sanitaire of recent acute hepatitis C in HIV-infected (HIV+) men who had sex with men (MSM). These cases for whom none of the usual bloodborne routes for hepatitis C (HCV) transmission was found, reported having had unprotected sex. In October 2004, we conducted a retrospective investigation in Parisian hospital wards to explore HCV modes of transmission in recent acute hepatitis C in HIV+ MSM. Patient demographics, clinical and biological status of HIV infection, reasons for HCV testing, sexual behaviour and risk factors for HCV transmission within the 6 months before hepatitis onset were collected from medical records. An anonymous self-administered questionnaire on sexual behaviour within the six months before hepatitis onset was also offered to all cases. We identified 29 cases of acute hepatitis C in HIV+ MSM with onset from April 2001 to October 2004. HIV infection was asymptomatic for 76%. Median age at hepatitis C onset was 40 (28-54) years. In all records, were noted unprotected anal sex, fisting in 21% and a concomitant sexually transmitted infection (STI) in 41%. Median time between HIV diagnosis and HCV infection was 6.5 years (0-22). From the 11 self-administered questionnaires completed, 10 reported an STI, 8 'hard' sexual practices, 6 bleeding during sex and 5 fisting. HCV transmission probably occurred through bleeding during unprotected traumatic anal sex among HIV+ MSM and may be facilitated by STI mucosal lesions. This report stresses the continuous need to strongly advocate safer sex to MSM. PMID:16077209

  16. Disruption of the Circadian Clock in Mice Increases Intestinal Permeability and Promotes Alcohol-Induced Hepatic Pathology and Inflammation

    PubMed Central

    Forsyth, Christopher B.; Shaikh, Maliha; Cavanaugh, Kate; Tang, Yueming; Vitaterna, Martha Hotz; Song, Shiwen

    2013-01-01

    The circadian clock orchestrates temporal patterns of physiology and behavior relative to the environmental light:dark cycle by generating and organizing transcriptional and biochemical rhythms in cells and tissues throughout the body. Circadian clock genes have been shown to regulate the physiology and function of the gastrointestinal tract. Disruption of the intestinal epithelial barrier enables the translocation of proinflammatory bacterial products, such as endotoxin, across the intestinal wall and into systemic circulation; a process that has been linked to pathologic inflammatory states associated with metabolic, hepatic, cardiovascular and neurodegenerative diseases – many of which are commonly reported in shift workers. Here we report, for the first time, that circadian disorganization, using independent genetic and environmental strategies, increases permeability of the intestinal epithelial barrier (i.e., gut leakiness) in mice. Utilizing chronic alcohol consumption as a well-established model of induced intestinal hyperpermeability, we also found that both genetic and environmental circadian disruption promote alcohol-induced gut leakiness, endotoxemia and steatohepatitis, possibly through a mechanism involving the tight junction protein occludin. Circadian organization thus appears critical for the maintenance of intestinal barrier integrity, especially in the context of injurious agents, such as alcohol. Circadian disruption may therefore represent a previously unrecognized risk factor underlying the susceptibility to or development of alcoholic liver disease, as well as other conditions associated with intestinal hyperpermeability and an endotoxin-triggered inflammatory state. PMID:23825629

  17. Serum lipase and amylase ratio in acute alcoholic and nonalcoholic pancreatitis by using Dupont ACA discrete clinical analyzer

    Microsoft Academic Search

    Ehsan Ansari; David A. Talenti; Joseph A. Scopelliti; Jawad M. Saadat; Bradley D. Zehr

    1996-01-01

    This work involves a retrospective analysis of serum amylase, lipase, and lipase\\/amylase ratio in alcoholic and nonalcoholic patients diagnosed with acute pancreatitis. The purpose of this study was to test the reliability of the Dupont ACA method with respect to the lipase\\/amylase ratio as a discriminator, for the etiology of pancreatitis. Thirty-six consecutive patients with the diagnosis of acute pancreatitis

  18. Reduced Susceptibility of DNA Methyltransferase 1 Hypomorphic (Dnmt1N/+) Mice to Hepatic Steatosis upon Feeding Liquid Alcohol Diet

    PubMed Central

    Yu, Lianbo; Zhang, Xiaoli; Majumder, Sarmila; Motiwala, Tasneem; Khan, Nuzhat; Belury, Martha; McClain, Craig; Jacob, Samson; Ghoshal, Kalpana

    2012-01-01

    Background Methylation at C-5 (5-mdC) of CpG base pairs, the most abundant epigenetic modification of DNA, is catalyzed by 3 essential DNA methyltransferases (Dnmt1, Dnmt3a and Dnmt3b). Aberrations in DNA methylation and Dnmts are linked to different diseases including cancer. However, their role in alcoholic liver disease (ALD) has not been elucidated. Methodology/Principal Findings Dnmt1 wild type (Dnmt1+/+) and hypomorphic (Dnmt1N/+) male mice that express reduced level of Dnmt1 were fed Lieber-DeCarli liquid diet containing ethanol for 6 weeks. Control mice were pair-fed calorie-matched alcohol-free liquid diet, and Dnmtase activity, 5-mdC content, gene expression profile and liver histopathology were evaluated. Ethanol feeding caused pronounced decrease in hepatic Dnmtase activity in Dnmt1+/+ mice due to decrease in Dnmt1 and Dnmt3b protein levels and upregulation of miR-148 and miR-152 that target both Dnmt1 and Dnmt3b. Microarray and qPCR analysis showed that the genes involved in lipid, xenobiotic and glutathione metabolism, mitochondrial function and cell proliferation were dysregulated in the wild type mice fed alcohol. Surprisingly, Dnmt1N/+ mice were less susceptible to alcoholic steatosis compared to Dnmt1+/+ mice. Expression of several key genes involved in alcohol (Aldh3b1), lipid (Ppara, Lepr, Vldlr, Agpat9) and xenobiotic (Cyp39a1) metabolism, and oxidative stress (Mt-1, Fmo3) were significantly (P<0.05) altered in Dnmt1N/+ mice relative to the wild type mice fed alcohol diet. However, CpG islands encompassing the promoter regions of Agpat9, Lepr, Mt1 and Ppara were methylation-free in both genotypes irrespective of the diet, suggesting that promoter methylation does not regulate their expression. Similarly, 5-mdC content of the liver genome, as measured by LC-MS/MS analysis, was not affected by alcohol diet in the wild type or hypomorphic mice. Conclusions/Significance Although feeding alcohol diet reduced Dnmtase activity, the loss of one copy of Dnmt1 protected mice from alcoholic hepatosteatosis by dysregulating genes involved in lipid metabolism and oxidative stress. PMID:22905112

  19. Immune responses to the hepatitis B surface antigen and liver-specific lipoprotein in acute type B hepatitis.

    PubMed Central

    Lee, W M; Reed, W D; Osman, C G; Vahrman, J; Zuckerman, A J; Eddleston, A L; Williams, R

    1977-01-01

    A serial prospective study of cellular immunity to HBsAg and liver-specific membrane lipoprotein was undertaken in 21 adults with acute hepatitis type B. Cellular immunity to HBsAg as determined by leucocyte migration inhibition with partially purified HBsAg as antigen was detected in all the patients during the recovery phase of the illness and was already detectable at the time of admission in 13 (62%) of the cases. In five of the remaining eight the titre of HBsAg in the serum at this time was high and in the whole series there was an inverse correlation between the degree of migration inhibition on admission and the peak HBsAg titre suggesting that antigen or possibly antigen/antibody complexes might be interfering with the demonstration of cellular immunity in vitro. Using a combination of minimum migration index recorded during the recovery period peak HBsAg titre, it was possible to compute the peak aspartate aminotransferase level with reasonable accuracy, a finding consistent with the hypothesis that the severity of the illness is related to both the number of infected hepatocytes and the vigour of the immune response to HBsAg. Evidence of an immune response to the liver-specific hepatocyte membrane lipoprotein was present in 50% of the patients tested at the time of admission, but was transient, having disappeared in every case by four weeks. The minimum migration index recorded with HBsAg as antigen was significantly lower in those with detectable sensitisation to the lipoprotein and it is possible that this autoimmune reaction is also generated by the interaction of T cells with viral antigenic determinants on the liver cell surface. PMID:856683

  20. Acute Liver Injury Induces Nucleocytoplasmic Redistribution of Hepatic Methionine Metabolism Enzymes

    PubMed Central

    Delgado, Miguel; Garrido, Francisco; Pérez-Miguelsanz, Juliana; Pacheco, María; Partearroyo, Teresa; Pérez-Sala, Dolores

    2014-01-01

    Abstract Aims: The discovery of methionine metabolism enzymes in the cell nucleus, together with their association with key nuclear processes, suggested a putative relationship between alterations in their subcellular distribution and disease. Results: Using the rat model of d-galactosamine intoxication, severe changes in hepatic steady-state mRNA levels were found; the largest decreases corresponded to enzymes exhibiting the highest expression in normal tissue. Cytoplasmic protein levels, activities, and metabolite concentrations suffered more moderate changes following a similar trend. Interestingly, galactosamine treatment induced hepatic nuclear accumulation of methionine adenosyltransferase (MAT) ?1 and S-adenosylhomocysteine hydrolase tetramers, their active assemblies. In fact, galactosamine-treated livers showed enhanced nuclear MAT activity. Acetaminophen (APAP) intoxication mimicked most galactosamine effects on hepatic MAT?1, including accumulation of nuclear tetramers. H35 cells that overexpress tagged-MAT?1 reproduced the subcellular distribution observed in liver, and the changes induced by galactosamine and APAP that were also observed upon glutathione depletion by buthionine sulfoximine. The H35 nuclear accumulation of tagged-MAT?1 induced by these agents correlated with decreased glutathione reduced form/glutathione oxidized form ratios and was prevented by N-acetylcysteine (NAC) and glutathione ethyl ester. However, the changes in epigenetic modifications associated with tagged-MAT?1 nuclear accumulation were only prevented by NAC in galactosamine-treated cells. Innovation: Cytoplasmic and nuclear changes in proteins that regulate the methylation index follow opposite trends in acute liver injury, their nuclear accumulation showing potential as disease marker. Conclusion: Altogether these results demonstrate galactosamine- and APAP-induced nuclear accumulation of methionine metabolism enzymes as active oligomers and unveil the implication of redox-dependent mechanisms in the control of MAT?1 subcellular distribution. Antioxid. Redox Signal. 20, 2541–2554. PMID:24124652

  1. Distinct Features in Natural History and Outcomes of Acute Hepatitis C

    PubMed Central

    Bunchorntavakul, Chalermrat; Jones, Lisa M.; Kikuchi, Masahiro; Valiga, Mary E.; Kaplan, David E.; Nunes, Frederick A.; Aytaman, Ayse; Reddy, K. Rajender

    2015-01-01

    Background: Acute hepatitis C (AHCV) provides a diagnostic challenge with diverse clinical presentations. Goals: This study was aimed to examine the clinical and demographic features as well as outcomes in AHCV patients identified from inpatient and outpatient hospital settings. Study: Patients with suspected AHCV were recruited from Philadelphia VA Medical Center, Hospital of University of Pennsylvania and Brooklyn VA Medical Center between 2000 and 2010. AHCV was diagnosed by acute serum alanine aminotransferase elevation with anti-hepatitis C virus (HCV) seroconversion, HCV-RNA fluctuations above 1 log, and/or recent high-risk exposure without prior HCV infection, excluding those with human immunodeficiency virus infection. Clinical and therapeutic outcomes were monitored for at least 6 months. Results: A total of 40 AHCV patients were enrolled with a median follow-up of 129 weeks. They were mostly men (68%) and whites (73%) with median age of 43 years, diverse risk factors (33% injection drugs, 20% health care–associated, 3% sexual, and 45% unknown), and wide variations in peak alanine aminotransferase (143 to 3435 U/L) and total bilirubin levels (0.4 to 19.3 mg/dL). Viremia resolved spontaneously in 23% and persisted without therapy in 27%, whereas 50% received interferon ?-based therapy with 90% cure (18/20). Distinct clinical scenarios included: (1) wide viremic fluctuations >1 log (65%) and intermittent HCV-RNA negativity; (2) autoantibodies (25% antinuclear antibodies, 69% antismooth muscle antibodies) or autoimmune features; (3) delayed spontaneous viral clearance in 2 patients; (4) rapid cirrhosis progression in 2 patients. Conclusions: AHCV is a heterogenous disease that requires careful monitoring. The lack of apparent risk factor in high proportion of patients and its diverse presentations warrant diagnostic vigilance. PMID:24457946

  2. Peginterferon alfa related psoriasis in a patient with acute hepatitis C and review of the literature.

    PubMed

    Dag, Muhammed Sait; Oztürk, Zeynel Abidin; Y?lmaz, Nimet; Cam, Hakan; Kaday?fç?, Abdurrahman

    2013-09-01

    The Interferon (IFN) which is the standard treatment for Hepatitis C, may cause a lot of side effects including dermatological anomalies. This paper presents a psoriasis case which occurred in relation with the treatment of acute hepatitis C (AHC) with peginterferon alfa (peg-IFN-?). A 60-year-old male patient came to the hospital with symptoms of high liver enzymes. The patient with history of a recent operation showed anti-HCV(+), HCVRNA 3.5 million IU/mL and HCV genotype 1b in the tests. Without any other etiological factors found in the patient, we started a treatment of peg-IFN?-2b with the diagnosis of AHC. After 3 weeks, psoriatic plaques were observed in various parts of the body. Antiviral treatment of the patient was concluded within 6 months. His psoriasis treatment initially commenced with local agents followed by phototherapy. Permanent viral response was seen in the patient and his lesions recovered rapidly after the antipsoriatic and antiviral treatment. Psoriasis and other autoimmune diseases should be considered even though they are encountered rarely,and the patients should be informed of the possible risks before planning treatment with peg-IFN-?. PMID:23912615

  3. Anti-viral therapy in hepatitis B virus reactivation with acute-on-chronic liver failure.

    PubMed

    Yuen, Man-Fung

    2015-07-01

    Hepatitis B virus (HBV) reactivation with hepatic decompensation leading to acute on chronic liver failure is not uncommon. It is associated with high mortality of up to 30-70 %. Prognostic factors for mortality include high bilirubin level, more prolonged prothrombin time, low platelet count and presence of pre-existing cirrhosis. Several studies addressing the efficacy of different anti-viral therapies, namely lamivudine, entecavir and tenofovir, have been performed. Although the results were not highly consistent, it appeared that use of anti-viral agents was associated with decreasing chance of mortality, subsequent HBV reactivation, disease progression, and with excellent viral suppression. The beneficial effects were most prominently observed in patients with MELD score 20-30. However, even with anti-viral therapy, patients may still have irreversible liver decompensation requiring liver transplantation if other adverse parameters. including pre-existing cirrhosis, bilirubin >20 mg/dL (340 µmol/L), prothrombin time <40 %, platelet count <120 × 10(9)/L. were present. Mortality rate in patients with MELD score >30 was >92 % even with prompt anti-viral treatment. Liver transplantation should be considered urgently. PMID:25788180

  4. An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure

    PubMed Central

    Tuñón, María Jesús; Alvarez, Marcelino; Culebras, Jesús M; González-Gallego, Javier

    2009-01-01

    Acute hepatic failure (AHF) is a severe liver injury accompanied by hepatic encephalopathy which causes multiorgan failure with an extremely high mortality rate, even if intensive care is provided. Management of severe AHF continues to be one of the most challenging problems in clinical medicine. Liver transplantation has been shown to be the most effective therapy, but the procedure is limited by shortage of donor organs. Although a number of clinical trials testing different liver assist devices are under way, these systems alone have no significant effect on patient survival and are only regarded as a useful approach to bridge patients with AHF to liver transplantation. As a result, reproducible experimental animal models resembling the clinical conditions are still needed. The three main approaches used to create an animal model for AHF are: surgical procedures, toxic liver injury and infective procedures. Most common models are based on surgical techniques (total/partial hepatectomy, complete/transient devascularization) or the use of hepatotoxic drugs (acetaminophen, galactosamine, thioacetamide, and others), and very few satisfactory viral models are available. We have recently developed a viral model of AHF by means of the inoculation of rabbits with the virus of rabbit hemorrhagic disease. This model displays biochemical and histological characteristics, and clinical features that resemble those in human AHF. In the present article an overview is given of the most widely used animal models of AHF, and their main advantages and disadvantages are reviewed. PMID:19575487

  5. Acute tolerance to alcohol impairment of behavioral and cognitive mechanisms related to driving: drinking and driving on the descending limb

    PubMed Central

    Weafer, Jessica

    2015-01-01

    Rationale Alcohol effects on behavioral and cognitive mechanisms influence impaired driving performance and decisions to drive after drinking (Barry 1973; Moskowitz and Robinson 1987). To date, research has focused on the ascending limb of the blood alcohol curve, and there is little understanding of how acute tolerance to impairment of these mechanisms might influence driving behavior on the descending limb. Objectives To provide an integrated examination of the degree to which alcohol impairment of motor coordination and inhibitory control contributes to driving impairment and decisions to drive on the ascending and descending limbs of the blood alcohol curve. Methods Social-drinking adults (N=20) performed a testing battery that measured simulated driving performance and willingness to drive, as well as mechanisms related to driving: motor coordination (grooved pegboard), inhibitory control (cued go/no-go task), and subjective intoxication. Performance was tested in response to placebo and a moderate dose of alcohol (0.65 g/kg) twice at comparable blood alcohol concentrations: once on the ascending limb and again on the descending limb. Results Impaired motor coordination and subjective intoxication showed acute tolerance, whereas driving performance and inhibitory control showed no recovery from impairment. Greater motor impairment was associated with poorer driving performance under alcohol, and poorer inhibitory control was associated with more willingness to drive. Conclusions Findings suggest that acute tolerance to impairment of motor coordination is insufficient to promote recovery of driving performance and that the persistence of alcohol-induced disinhibition might contribute to risky decisions to drive on the descending limb. PMID:21960182

  6. Prevalence of hepatitis B and C viruses infection in chronic alcoholics with or without liver disease in Ioannina, Greece: Low incidence of HCV infection

    Microsoft Academic Search

    Georgios N. Dalekos; Eleftheria Zervou; Markos H. Merkouropoulos; Epameinondas V. Tsianos

    1996-01-01

    Intravenous heroin abusers comprise a high risk group for hepatitis B and C viruses (HBV and HCV) infection. Chronic alcoholics with liver disease (LD) also comprise a high risk group for HBV infection whereas the frequency of antibodies to HCV (anti-HCV) ranges from 27–42.6%. In this study, HBV and HCV infection markers were determined in alcoholic patients with (83 patients)

  7. Zeaxanthin Dipalmitate Therapeutically Improves Hepatic Functions in an Alcoholic Fatty Liver Disease Model through Modulating MAPK Pathway

    PubMed Central

    Xing, Feiyue; Han, Tao; Jiao, Rui; Liong, Emily C.; Fung, Man-Lung; So, Kwok-Fai; Tipoe, George L.

    2014-01-01

    In the current study, the therapeutic effects of zeaxanthin dipalmitate (ZD) on a rat alcoholic fatty liver disease (AFLD) model were evaluated. After-treatment with ZD from the 5th week to the 10th week in a 10-week ethanol intragastric administration in rats significantly alleviated the typical AFLD symptoms, including reduction in rat body weight, accumulation of hepatic fat droplets, occurrence of oxidative stress, inflammation, chemoattractive responses and hepatic apoptosis in the liver. The reduction of liver function abnormalities by ZD was partly through lower expression level of cytochrome P450 2E1 (CYP2E1), diminished activity of nuclear factor kappa B (NF-?B) through the restoration of its inhibitor kappa B alpha (I?B?), and the modulation of MAPK pathways including p38 MAPK, JNK and ERK. ZD treatment alone did not pose obvious adverse effect on the healthy rat. In the cellular AFLD model, we also confirmed the inhibition of p38 MAPK and ERK abolished the beneficial effects of ZD. These results provide a scientific rationale for the use of zeaxanthin and its derivatives as new complementary agents for the prevention and treatment of alcoholic liver diseases. PMID:24740309

  8. The effects of acute alcohol exposure on the response properties of neurons in visual cortex area 17 of cats

    SciTech Connect

    Chen Bo [Hefei National Laboratory for Physical Sciences at Microscale and School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027 (China); State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Science, Beijing 100101 (China); Xia Jing; Li Guangxing [Hefei National Laboratory for Physical Sciences at Microscale and School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027 (China); Zhou Yifeng, E-mail: zhouy@ustc.edu.c [Hefei National Laboratory for Physical Sciences at Microscale and School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027 (China); State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Science, Beijing 100101 (China)

    2010-03-15

    Physiological and behavioral studies have demonstrated that a number of visual functions such as visual acuity, contrast sensitivity, and motion perception can be impaired by acute alcohol exposure. The orientation- and direction-selective responses of cells in primary visual cortex are thought to participate in the perception of form and motion. To investigate how orientation selectivity and direction selectivity of neurons are influenced by acute alcohol exposure in vivo, we used the extracellular single-unit recording technique to examine the response properties of neurons in primary visual cortex (A17) of adult cats. We found that alcohol reduces spontaneous activity, visual evoked unit responses, the signal-to-noise ratio, and orientation selectivity of A17 cells. In addition, small but detectable changes in both the preferred orientation/direction and the bandwidth of the orientation tuning curve of strongly orientation-biased A17 cells were observed after acute alcohol administration. Our findings may provide physiological evidence for some alcohol-related deficits in visual function observed in behavioral studies.

  9. Please cite this article in press as: X. Chen, et al. Dynamics of acute hepatitis B virus infection in chimpanzees, Math. Comput. Simul. (2013), http://dx.doi.org/10.1016/j.matcom.2013.05.003

    E-print Network

    Kuang, Yang

    2013-01-01

    is the most serious type of viral hepatitis. About two billion people worldwide have been infectedPlease cite this article in press as: X. Chen, et al. Dynamics of acute hepatitis B virus infection in Simulation xxx (2013) xxx­xxx Original article Dynamics of acute hepatitis B virus infection in chimpanzees

  10. Biochemical Evaluation of Patients of Alcoholic Liver Disease and Non-alcoholic Liver Disease.

    PubMed

    Torkadi, Prasad P; Apte, I C; Bhute, A K

    2014-01-01

    Alcoholic liver disease (ALD) is due to excessive alcohol intake for long duration. Distinguishing ALD from non-ALD (non-alcoholic steatohepatitis, hepatitis of viral origin) is difficult as patient may deny alcohol abuse. Clinical examination, histology and serology may not differentiate these conditions. Accurate diagnosis is important as management of ALD differs from non-ALD patients. The aim of our study was (1) To evaluate the patients of ALD and non-ALD by biochemical parameters compared to controls, (2) To assess whether these parameters can differentiate ALD from non-ALD. Study was carried out on 50 patients of ALD in group I and 35 patients of NASH (non-alcoholic steatohepatitis) and acute viral hepatitis each in group II. Age matched healthy controls n = 50. Selection criteria-history of alcohol intake (amount and duration), clinical examination, sonography of abdomen, serum alanine transaminase (ALT) and bilirubin levels. Blood samples were analyzed for bilirubin, aspartate transaminase (AST), ALT, alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) by kinetic method. Statistical analysis was done by Student unpaired 't' test. Patients of ALD have raised AST/ALT ratio (De Ritis ratio) (>2), ALP and GGT compared to controls (P < 0.01).There is significant difference in AST/ALT ratio, serum GGT and ALP in ALD group compared to that in NASH and acute viral hepatitis (P < 0.05). This study suggests that De Ritis ratio >2 in ALD patients may be due to alcohol induced hepatic mitochondrial injury and pyridoxine deficiency. High GGT and ALP values may indicate enzyme induction by alcohol and mild cholestasis. Thus ALD patients have severe hepatic damage. De Ritis ratio <1 and normal to mild elevation in GGT level in NASH and acute viral hepatitis suggest mild hepatic injury of non-alcoholic origin. Our study concludes that ALD patients can be differentiated from NASH and acute viral hepatitis with certainty by measuring serum AST/ALT ratio, GGT and ALP. These biochemical parameters may help clinicians to support the diagnosis of ALD and non-ALD. PMID:24478554

  11. Acute effects of alcohol on feedback processing and outcome evaluation during risky decision-making: an ERP study

    Microsoft Academic Search

    Anja S. Euser; Catharina S. van Meel; Michelle Snelleman; Ingmar H. A. Franken

    2011-01-01

    Rationale  Although risky decision-making is one of the hallmarks of alcohol use disorders, relatively little is known about the acute\\u000a psychopharmacological effects of alcohol on decision-making processes.\\u000a \\u000a \\u000a \\u000a \\u000a Objective  The present study investigated the acute effects of alcohol on neural mechanisms underlying feedback processing and outcome\\u000a evaluation during risky decision-making, using event-related brain potentials (ERPs).\\u000a \\u000a \\u000a \\u000a \\u000a Methods  ERPs elicited by positive and negative feedback were

  12. Alcohol-induced hepatic sinusoidal endothelial cell dysfunction in the mouse is mediated by Kupffer cells

    Microsoft Academic Search

    Ion. V. Deaciuc; Nympha B. D'Souza; John J. Spitzer

    1995-01-01

    Significant increase in plasma hyaluronan level (104%) and a marked inhibition of hyaluronan uptake by the isolated, perfused liver (54%) were seen 3 h after intraperitoneal administration of alcohol (4.4 g\\/kg body wt.) to mice. Intravenous administration of GdCl3 (10 mg\\/kg body wt.), an agent that inactivates\\/eliminates Kupffer cells, 24 h prior to alcohol administration, counteracted the alcohol-induced suppression of

  13. Nature and prevalence of risk factors associated to type B and C acute viral hepatitis cases in Bucharest, 1998-2000.

    PubMed

    Ion-Nedelcu, N; Velea, L; Ulmeanu, V; Dragomirescu, C; Dumitrache-Marian, R; Gherasim, P; Iord?chescu, C; Mihailovici, R; Radu, L

    2001-01-01

    The main objective of the study was to calculate and report the prevalence of probable risk factors involved in the transmission of pathogenic agents among type B and C acute viral hepatitis cases confirmed in Bucharest (1998-2000). The standardized values of the risks detected in the 45-180 days preceding the onset of illness suggest that in both types of acute viral hepatitis considered in our study transmission associated to the individuals' behaviour (19.0%-hepatitis B and 20.1%-hepatitis C) seems more frequent than "iatrogenic" transmission; in case of hepatitis B, sexual contacts with more than one partner coming first (15.7%), whilst in case of hepatitis C the use of i.v. drugs (heroine) was most frequently incriminated (12.4%). The study reviews the present knowledge of the risk factors involved in the transmission of the disease and approaches prevention strategies. PMID:11850898

  14. Phosphorus-31 nuclear magnetic resonance spectroscopic study of the canine pancreas: applications to acute alcoholic pancreatitis

    SciTech Connect

    Janes, N.; Clemens, J.A.; Glickson, J.D.; Cameron, J.L.

    1988-01-01

    The first nuclear magnetic resonance spectroscopic study of the canine pancreas is described. Both in-vivo, ex-vivo protocols and NMR observables are discussed. The stability of the ex-vivo preparation based on the NMR observables is established for at least four hours. The spectra obtained from the in-vivo and ex-vivo preparations exhibited similar metabolite ratios, further validating the model. Metabolite levels were unchanged by a 50% increase in perfusion rate. Only trace amounts of phosphocreatine were observed either in the intact gland or in extracts. Acute alcoholic pancreatitis was mimicked by free fatty acid infusion. Injury resulted in hyperamylasemia, edema (weight gain), increased hematocrit and perfusion pressure, and depressed levels of high energy phosphates.

  15. Unsaturated fatty acid feeding prevents the development of acute hepatitis in Long-Evans cinnamon (LEC) rats.

    PubMed

    Shibata, T; Nagayasu, H; Kawano, T; Kitajo, H; Hamada, J; Moriuchi, T; Okada, F; Watanabe, S; Yasuda, S; Okuyama, H; Kobayashi, H; Arisue, M

    1999-01-01

    To investigate the effects of dietary alpha-linolenic acid (18:3, n-3; alpha-LNA) and linoleic acid (18:2, n-6; LA) on the development of hereditary hepatitis, we compared incidences and grades of acute hepatitis between the Long-Evans cinnamon (LEC) rats fed with safflower oil-supplemented diet and perilla oil-supplemented diet. Both safflower and perilla oil supplemented diets reduced the incidence of hepatitis and significantly prolonged its onset as compared to the non-supplemented conventional diet. No significant difference was observed between safflower and perilla oil diets in the rats of incidence of hepatitis. At the age of 16 weeks, just before the onset of hepatitis, serum levels of transaminase (AST, ALT) and concentration of copper in rats fed with both test diets were significantly reduced as compared with that of rats fed alpha-linolenate and linoleate have an inhibitory effect on the development of hepatitis in LEC rats due to the prevention of serum copper elevation. PMID:10697529

  16. The effects of acute alcohol consumption and eccentric muscle damage on neuromuscular function.

    PubMed

    Barnes, Matthew J; Mündel, Toby; Stannard, Stephen R

    2012-02-01

    Voluntary and electrically stimulated muscular performance was examined to identify the effects of acute alcohol consumption on neuromuscular function in the presence and absence of exercise-induced muscle damage (EIMD). After initial neuromuscular performance measures were made, 12 subjects completed a bout of eccentric exercise (EX) using the quadriceps muscles of 1 leg while the remaining 11 subjects did not exercise (NX). Subjects then consumed either an alcoholic beverage containing 1 g·kg(-1) body weight (ALC) or a nonalcoholic beverage (OJ). On another occasion the contralateral leg of both groups was tested and those in the EX group performed an equivalent bout of eccentric exercise after which the other beverage was consumed. Measurements of neuromuscular function were made pre-exercise and 36 and 60 h post-beverage consumption. Creatine kinase (CK) was measured pre-exercise and at 12, 36, and 60 h. Significantly greater (p < 0.01) decrements in maximal voluntary isometric contraction were observed with EX ALC at 36 and 60 h compared with EX OJ, and no change was seen in the NX group. Significant decreases in voluntary activation were observed at 36 h (p = 0.003) and 60 h (p = 0.01) with EX ALC only. Elevations in CK were observed at all posteccentric exercise time points (all p < 0.05) under both EX OJ and ALC. No change in electromyography or low-frequency fatigue was observed under either treatment in either group. These results suggest that decreased neural drive appears to contribute to alcohol's effect on the magnitude of EIMD-related decrements in voluntary force generation. PMID:22185621

  17. CHRONIC ALCOHOL CONSUMPTION HAS BIPHASIC EFFECTS ON HEPATIC INSULIN SIGNALING DEPENDENT ON DOSE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiological studies have shown paradoxical biphasic effects of alcohol on health. Moderate drinkers have lower overall mortality than teetotalers or than heavy drinkers. There are protective effects of low levels of alcohol consumption (less than one drink day) on diabetes risk and other chroni...

  18. Successful management of hepatic mucormycosis in an acute lymphoblastic leukaemia patient: a case report and review of the literature.

    PubMed

    Tuysuz, Gulen; Ozdemir, Nihal; Senyuz, Osman Faruk; Emre, Senol; Kantarcioglu, Serda; Adaletli, Ibrahim; Kepil, Nuray; Tutuncu, Cigdem; Celkan, Tiraje

    2014-08-01

    We present a case of hepatic mucormycosis in a 9-year-old boy with acute lymphoblastic leukaemia. Despite long-term use of combined liposomal amphotericin B and posaconazole therapy, the lesion persisted and could only be treated by surgical excision. After surgery, antifungal treatment was continued with posaconazole. On follow-up, the patient had two episodes of ascending cholangitis which were responsive to intravenous antibiotics. He is doing well at the moment in remission for 2.5 years. Mucormycosis was long regarded as a fatal infection with poor prognosis. With early medical and surgical management, survival rates increase. Isolated hepatic mucormycosis is rare and only seven cases were reported in the literature up to now. We wanted to emphasise the role of early surgery in patients with hepatic mucormycosis in view of the literature. PMID:24635874

  19. Chronic Graft-versus-Host Disease of the Liver Presenting as an Acute Hepatitis following Nonmyeloablative Hematopoietic Stem Cell Transplantation

    Microsoft Academic Search

    Hoyoung Maeng; Jae-Hyun Lee; June Won Cheong; Seung Tae Lee; Jee Sook Hahn; Yun Woong Ko; Yoo Hong Min

    2004-01-01

    Chronic graft-versus-host disease (GVHD) of the liver usually presents as an indolent cholestatic disease. We observed 3 patients\\u000a in whom chronic GVHD of the liver after allogeneic nonmyeloablative hematopoietic stem cell transplantation (HSCT) presented\\u000a with marked elevations of serum aminotransferases, clinically resembling acute viral hepatitis. The liver biopsies revealed\\u000a predominant diffuse lobular injury and degenerative small bile ducts. Prompt administration

  20. Antibody responses to Hepatitis B and measles-mumps-rubella vaccines in children who received chemotherapy for acute lymphoblastic leukemia

    PubMed Central

    Viana, Simone Santana; Araujo, Gustavo Santos; Faro, Gustavo Baptista de Almeida; da Cruz-Silva, Lana Luíza; Araújo-Melo, Carlos André; Cipolotti, Rosana

    2012-01-01

    Objective To evaluate viral vaccine antibody levels in children with acute lymphoblastic leukemia after chemotherapy and after vaccine booster doses. Methods Antibody levels against hepatitis B, rubella, measles and mumps vaccine antigens were evaluated in 33 children after completing chemotherapy (before and after vaccine booster doses) and the results were compared to the data of 33 healthy children matched for gender, age and social class. Results After chemotherapy, 75.9%, 67.9%, 59.3% and 51.7% of the patients showed low antibody titers that would be unlikely to protect against exposure to measles, rubella, hepatitis B and mumps, respectively. After receiving a vaccine booster dose for these antigens the patients had high antibody levels consistent with potential protection against measles, mumps and hepatitis B, but not against rubella. Conclusion Extra doses of measles-mumps-rubella plus hepatitis B vaccines are recommended in acute lymphoblastic leukemia patients submitted to treatment after hematologic recovery. After this, viral vaccine antibody levels should be verified to define the individual's protective status. PMID:23049440

  1. 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

  2. Application of an alcohol clamp paradigm to examine inhibitory control, subjective responses, and acute tolerance in late adolescence.

    PubMed

    Hendershot, Christian S; Wardell, Jeffrey D; Strang, Nicole M; Markovich, Mike S D; Claus, Eric D; Ramchandani, Vijay A

    2015-06-01

    Individual differences in acute alcohol effects on cognitive control and subjective responses-and acute tolerance to these effects-are implicated in the risk for heavy drinking and alcohol-related harms. Few studies have examined these effects in drinkers under age 21. Additionally, studies of acute tolerance typically involve bolus oral alcohol administration, such that estimates of tolerance are confounded with blood alcohol concentration (BAC) limb. The current study examined cognitive control and subjective responses in young heavy drinkers (n = 88; M = 19.8 years old, SD = 0.8) during a single-session alcohol clamp protocol. Participants completed an intravenous alcohol session comprising an ascending limb (0 to 80 mg% in 20 min) and a BAC plateau (80 mg% for 80 min). Serial assessments included a cued go/no-go task and measures of stimulation, sedation, and craving. Relevant individual difference factors (attention-deficit hyperactivity disorder [ADHD] symptoms and sensation seeking) were examined as moderators. Multilevel modeling demonstrated that response inhibition worsened following initial rise in BAC and showed increasing impairment during the BAC plateau. ADHD symptoms and sensation seeking moderated this effect. Significant within-person associations between stimulation and craving were evident on the ascending limb only. Participants with higher ADHD symptoms reported steeper increases in stimulation during the ascending limb. These findings provide initial information about subjective and behavioral responses during pseudoconstant BAC, and potential moderators of these outcomes, in late adolescence. Additional studies with placebo-controlled designs are necessary to confirm these findings. (PsycINFO Database Record PMID:26053322

  3. Alcohol

    MedlinePLUS

    ... risk. Because alcohol can cause such problems, the citizens and government leaders in the United States decided ... The Nemours Foundation, iStock, Getty Images, Corbis, Veer, Science Photo Library, Science Source Images, Shutterstock, and Clipart. ...

  4. Alcohol

    Microsoft Academic Search

    William E. M. Lands

    \\u000a \\u000a \\u000a Key Points\\u000a \\u000a \\u000a \\u000a • \\u000a \\u000a \\u000a Excessive alcohol consumption contributes to 4 of the 10 leading causes of death in the United States.\\u000a \\u000a \\u000a \\u000a • \\u000a \\u000a \\u000a Alcohol consumption is split, with 33% of the population consuming 95% of the alcoholic beverages and 33% abstaining. The\\u000a US population median intake is much less than the average (mean) intake.\\u000a \\u000a \\u000a \\u000a \\u000a • \\u000a \\u000a \\u000a An increase in average alcohol intake could

  5. Alcohol

    MedlinePLUS

    ... created when grains, fruits, or vegetables are fermented . Fermentation is a process that uses yeast or bacteria ... change the sugars in the food into alcohol. Fermentation is used to produce many necessary items — everything ...

  6. Alcohol.

    ERIC Educational Resources Information Center

    Schibeci, Renato

    1996-01-01

    Describes the manufacturing of ethanol, the effects of ethanol on the body, the composition of alcoholic drinks, and some properties of ethanol. Presents some classroom experiments using ethanol. (JRH)

  7. Protective effects of caffeic acid phenethyl ester against acute radiation-induced hepatic injury in rats.

    PubMed

    Chu, JianJun; Zhang, Xiaojun; Jin, Liugen; Chen, Junliang; Du, Bin; Pang, Qingfeng

    2015-03-01

    Caffeic acid phenyl ester (CAPE) is a potent anti-inflammatory agent and it can eliminate the free radicals. The current study was intended to evaluate the protective effect of CAPE against the acute radiation-induced liver damage in rats. Male Sprague-Dawley rats were intraperitoneally administered with CAPE (30 mg/kg) for 3 consecutive days before exposing them to a single dose of 30 Gy of ?-ray irradiation to upper abdomen. We found that pretreatment with CAPE significantly decreased the serum levels of alanine aminotransferase and aspartate aminotransferase and increased the activity of superoxide dismutase and glutathione. Histological evaluation further confirmed the protection of CAPE against radiation-induced hepatotoxicity. TUNEL assay showed that CAPE pretreatment inhibited hepatocyte apoptosis. Moreover, CAPE inhibited the nuclear transport of NF-?B p65 subunit, decreased the level of tumor necrosis factor-?, nitric oxide and inducible nitric oxide synthase. Taken together, these results suggest that pretreatment with CAPE offers protection against radiation-induced hepatic injury. PMID:25704035

  8. Hepatoprotective effect of nitric oxide in experimental model of acute hepatic failure

    PubMed Central

    Saracyn, Marek; Brytan, Marek; Zdanowski, Robert; Z?bkowski, Tomasz; Dyrla, Przemys?aw; Patera, Janusz; Wojtu?, Stanis?aw; Koz?owski, Wojciech; Wa?kowicz, Zofia

    2014-01-01

    AIM: To evaluate the effect of nitric oxide (NO) on the development and degree of liver failure in an animal model of acute hepatic failure (AHF). METHODS: An experimental rat model of galactosamine-induced AHF was used. An inhibitor of NO synthase, nitroarginine methyl ester, or an NO donor, arginine, were administered at various doses prior to or after the induction of AHF. RESULTS: All tested groups developed AHF. Following inhibition of the endogenous NO pathway, most liver parameters improved, regardless of the inhibitor dose before the induction of liver damage, and depending on the inhibitor dose after liver damage. Prophylactic administration of the inhibitor was more effective in improving liver function parameters than administration of the inhibitor after liver damage. An attempt to activate the endogenous NO pathway prior to the induction of liver damage did not change the observed liver function parameters. Stimulation of the endogenous NO pathway after liver damage, regardless of the NO donor dose used, improved most liver function parameters. CONCLUSION: The endogenous NO pathway plays an important role in the development of experimental galactosamine-induced AHF. PMID:25516652

  9. How CAGE, RAPS4-QF, and AUDIT Can Help Practitioners for Patients Admitted with Acute Alcohol Intoxication in Emergency Departments?

    PubMed Central

    Brousse, Georges; Arnaud, Benjamin; Geneste, Julie; Pereira, Bruno; De Chazeron, Ingrid; Teissedre, Frederique; Perrier, Christophe; Schwan, Raymund; Malet, Laurent; Schmidt, Jeannot; Llorca, Pierre Michel; Cherpitel, Cheryl J.

    2014-01-01

    Aims: To help clinicians to identify the severity of alcohol use disorders (AUDs) from optimal thresholds found for recommended scales. Especially, taking account of the high prevalence of alcohol dependence among patients admitted to the emergency department (ED) for acute alcohol intoxication (AAI), we propose to define thresholds of severity of dependence based on the AUDIT score. Methods: All patients admitted to the ED with AAI (blood alcohol level >0.8?g/L), in a 2-month period, were assessed using the CAGE, RAPS-QF, and AUDIT, with the alcohol dependence/abuse section of the mini international neuropsychiatric interview (MINI) used as the gold standard. To explore the relation between the AUDIT and the MINI the sum of the positive items on the MINI (dependence) as a quantitative variable and as an ordinal parameter were analyzed. From the threshold score found for each scale we proposed intervals of severity of AUDs. Results: The mean age of the sample (122 males, 42 females) was 46?years. Approximately 12% of the patients were identified with alcohol abuse and 78% with dependence (DSM-IV). Cut points were determined for the AUDIT in order to distinguish mild and moderate dependence from severe dependence. A strategy of intervention based on levels of severity of AUD was proposed. Conclusion: Different thresholds proposed for the CAGE, RAPS4-QF, and AUDIT could be used to guide the choice of intervention for a patient: brief intervention, brief negotiation interviewing, or longer more intensive motivational intervention. PMID:25009509

  10. 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 ...

  11. Predicting Short-term Mortality and Long-term Survival of Hospitalized U.S. Patients with Alcoholic Hepatitis

    PubMed Central

    Cuthbert, Jennifer A.; Arslanlar, Sami; Yepuri, Jay; Montrose, Marc; Ahn, Chul W.; Shah, Jessica P.

    2014-01-01

    Background No study has evaluated current scoring systems for their accuracy in predicting short- and long-term outcome of alcoholic hepatitis in a U.S. population. Methods We reviewed electronic records for patients with ALD admitted to Parkland Memorial Hospital between January 2002 and August 2005. Data and outcomes for 148 of 1761 admissions meeting pre-defined criteria were collected. The discriminant function (DF) was revised (INRdf) to account for changes in prothrombin time reagents that could potentially affect identification of risk using the prior DF threshold of > 32. Admission and theoretical peak scores using the Model for End-stage Liver Disease (MELD) were calculated. Analysis models compared 5 different scoring systems. Results INRdf was closely correlated with the old DF (r2 = 0.95). Multivariate analysis of data showed that survival at 28 days was significantly associated with admission values for white blood cell count (p = 0.006), a scoring system using a combination of age, bilirubin, coagulation status and creatinine (p < 0.001) as well as an elevated ammonia result within 2 days of admission (p = 0.006). When peak values for MELD were included, they were the most significant predictor of short-term mortality (p < 0.001) followed by INRdf (p = 0.006 Conclusion On admission, 2 scoring systems that identify a subset of patients with severe alcoholic liver disease are able to predict > 50% mortality at 4 weeks as well as > 80% mortality at 6 months without specific treatment. PMID:24445730

  12. B cell gene signature with massive intrahepatic production of antibodies to hepatitis B core antigen in hepatitis B virus–associated acute liver failure

    PubMed Central

    Farci, Patrizia; Diaz, Giacomo; Chen, Zhaochun; Govindarajan, Sugantha; Tice, Ashley; Agulto, Liane; Pittaluga, Stefania; Boon, Denali; Yu, Claro; Engle, Ronald E.; Haas, Mark; Simon, Richard; Purcell, Robert H.; Zamboni, Fausto

    2010-01-01

    Hepatitis B virus (HBV)-associated acute liver failure (ALF) is a dramatic clinical syndrome due to a sudden loss of hepatic cells leading to multiorgan failure. The mechanisms whereby HBV induces ALF are unknown. Here, we show that liver tissue collected at the time of liver transplantation in two patients with HBV-associated ALF is characterized by an overwhelming B cell response apparently centered in the liver with massive accumulation of plasma cells secreting IgG and IgM, accompanied by complement deposition. We demonstrate that the molecular target of these antibodies is the hepatitis B core antigen (HBcAg); that these anti-bodies display a restricted variable heavy chain (VH) repertoire and lack somatic mutations; and that these two unrelated individuals with ALF use an identical predominant VH gene with unmutated variable domain (IGHV1-3) for both IgG and IgM anti-HBc antibodies, indicating that HBcAg is the target of a germline human VH gene. These data suggest that humoral immunity may exert a primary role in the pathogenesis of HBV-associated ALF. PMID:20421498

  13. Human immunodeficiency virus, hepatitis C, and inflammatory biomarkers in individuals with alcohol problems: a cross-sectional study

    PubMed Central

    2013-01-01

    Background Assessing whether hepatitis C (HCV) co-infection with human immunodeficiency virus (HIV) is associated with increased inflammation is complex. The liver, integral to inflammatory biomarker synthesis, is compromised by HCV and alcohol abuse. Using single liver-synthesized biomarkers (e.g. C-reactive protein) to represent inflammation may not be appropriate in HIV/HCV co-infection. We hypothesized that 1) detectable HIV/HCV RNA was independently associated with increased inflammation; 2) a composite inflammation measure describes inflammation differently from single inflammatory biomarkers. Methods We compared inflammation by HIV/HCV group in a cohort of 361 HIV infected participants from the HIV-Longitudinal Interrelationships of Viruses and Ethanol study. Inflammatory biomarkers >75th percentile were considered elevated. Associations between HIV/HCV group and elevated biomarkers were analyzed as a composite measure (inflammatory burden) or individually. We defined inflammatory burden as number of concurrently elevated biomarkers. Biomarkers included interleukin-6 (IL-6), C-reactive protein (CRP), cystatin C, serum amyloid-A (SAA), tumor necrosis factor-alpha (TNF-?), interleukin-10 (IL-10). Covariates: alcohol, liver fibrosis, comorbidities, CD4 count, antiretroviral therapy, substance use. Results Detectable HIV and HCV RNA (OR?=?2.49; 95% CI?=?1.05–5.89) and detectable HCV RNA alone (2.95; 1.08–8.01) were independently associated with increased odds of having a greater inflammatory burden compared to undetectable viremia. Elevated IL-10 (7.79; 1.90–31.97) and TNF-? (7.70; 1.42–41.83) were independently associated with detectable HIV and HCV RNA. Elevated IL-10 was also associated with detectable HCV RNA alone (5.51; 1.17, 25.84). Conclusions Detectable HIV and HCV replication versus undetectable replication was associated with inflammatory burden and certain inflammatory biomarkers independently of alcohol consumption, liver fibrosis and other comorbidities. PMID:23987993

  14. Goal-related outcome after acute alcohol-pancreatitis -- a two-year follow-up study.

    PubMed

    Lappalainen-Lehto, Riitta; Koistinen, Noora; Aalto, Mauri; Huhtala, Heini; Sand, Juhani; Nordback, Isto; Seppä, Kaija

    2013-12-01

    The aim of this study was to find out if an acute pancreatitis leads the patients to reduce their alcohol consumption and if there are factors predicting the outcome. We also observed which factors affected the choice of patient's personal drinking goal, e.g., abstinence or moderate drinking, how this goal changed during the follow-up and how the goal affected the change in drinking habits. In 2001-2005, 120 patients treated in Tampere University Hospital for their first alcohol-related acute pancreatitis were interviewed before discharge from the hospital and at the two-year follow-up. All patients had at least one intervention session for their alcohol use. Of the patients 87 (72.5%) completed the study. The alcohol consumption level and its changes, personal drinking goal of the patients, the factors affecting the choice and the changes of the goal were observed. Most (96.4%) of the patients were willing to reduce their drinking. At follow-up, 34 (40.5%) patients succeeded in reducing their alcohol consumption under the pre-set moderate drinking level. The only factor predicting alcohol use was the number of hospitalization days due to the acute alcohol-related pancreatitis (p=0.015). Those who chose abstinence seemed to succeed more often in stopping drinking or reducing their drinking below risk levels as compared to those with moderation goal (47.9% vs. 28.6%, p=0.075). The only abstinence-goal predicting factor was the concern of the relatives, friends or doctors (p=0.001). All 6 patients who needed intensive care chose abstinence-goal. During the follow-up period the goal changed. At baseline, the majority chose abstinence but two years after pancreatitis, the majority was striving for moderate drinking. A serious illness seems to be a good opportunity to change and to motivate patients. Even if abstinence is recommended to patients with alcohol-related pancreatitis, communication of individual goals is important in the motivation process of the patients. PMID:24018221

  15. 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 ...

  16. Effect of acute and chronic alcohol treatment and their superimposition on lysosomal, cytoplasmic, and proteosomal protease activities in rat skeletal muscle in vivo

    Microsoft Academic Search

    M. Koll; S. Ahmed; D. Mantle; T. M. Donohue; T. N. Palmer; U. A. Simanowski; H. K. Seltz; T. J. Peters; V. R. Preedy

    2002-01-01

    Alcohol can be considered as a nutritional toxin when ingested in excess amounts and leads to skeletal muscle myopathy. We hypothesized that altered protease activities contribute to this phenomenon, and that differential effects on protease activities may occur when: (1) rats at different stages in their development are administered alcohol in vivo; (2) acute ethanol treatment is superimposed on chronic

  17. Expectancy and tolerance: a study of acute alcohol intoxication using the balanced placebo design.

    PubMed

    Laberg, J C; Löberg, T

    1989-09-01

    Interactive effects of expectancy and alcohol dose on CNS functioning were examined in subjects differing in degree of dependence on alcohol, using the balanced placebo design. Male subjects (N = 30), 10 severely-, 10 moderately- and 10 nondependent on alcohol, were tested with the Klove-Matthews Motor Steadiness Battery before and after drinking. The administered alcohol dose yielded .07 mg/dl mean blood alcohol level. Expectations about alcohol resulted in impaired sensorimotor coordination in severely dependent alcoholics, as compared to expectations of soft drinks. Moderately dependent subjects showed an opposite response pattern. Such expectancy factors may counteract neuropharmacological tolerance effects, neutralizing real tolerance effects on moderate doses of alcohol for severely dependent alcoholics. High tolerance also makes larger quantities necessary, leading to increased consumption to obtain the same effect. PMID:2779247

  18. Acute aquatic toxicity of nine alcohol ethoxylate surfactants to fathead minnow and Daphnia magna

    SciTech Connect

    Wong, D.C.L.; Dorn, P.B.; Chai, E.Y. [Shell Development Co., Houston, TX (United States)

    1995-12-31

    The aquatic toxicity of nine commercial-grade alcohol ethoxylate surfactants was studied in acute exposures to fathead minnow (Pimephales promelas) and Daphnia magna. All studies were conducted in accordance with USEPA TSCA Good Laboratory Practice Standards. Mean measured surfactant concentrations in exposure solutions showed good agreement with nominal concentrations for both fathead minnow and daphnid tests. Surfactant recoveries ranged from 59 to 97% and 67 to 106% in the fathead minnow and daphnid solutions, respectively. The response of both species to the surfactants was generally similar with the daphnids being slightly more sensitive to a few surfactants. Surfactant toxicity tended to increase with increasing alkyl chain lengths. The effect of low average EO groups on increased surfactant toxicity was more evident in the daphnid exposures. Quantitative structure-activity relationship (QSAR) models were developed form the data which relates surfactant structure to toxicity. The models predict increasing toxicity with decreasing EO number and increasing alkyl chain length. The models also indicate that alkyl chain length has a greater effect on toxicity than EO groups. Further, the models indicate that both species did not differ markedly in their sensitivity to alkyl chain length effects, while the number of EO groups had a stronger effect on daphnids than fathead minnow. Good agreement was found between QSAR model-predicted toxicity and reported toxicity values from the literature for several surfactants previously studied.

  19. [Impact of acute alcoholism on the women's mortality in the northern region of Slovak Republic].

    PubMed

    Straka, L; Stuller, F; Novomeský, F; Zelený, M

    2009-10-01

    Problem of women's alcoholism doesn't belong among main topics of Slovak or Czech public discussions. Though everyone meeting the phenomenon of women's alcoholism can feel the fatal consequences of this mistake, our society used to perceive alcoholism as a men's problem. The authors performed the complex analysis of the mortuary files with particular focusing on the cases of women's deaths caused by alcohol intoxication, and the cases of deaths where an alcohol played the dominating role, in the northern regions of Slovak republic. Submitted article is author's next referring to urgent need of public discussion concerning the alcohol consumption in Slovakia, the phenomenon being widely tolerated by the society. PMID:20302040

  20. Doppler Ultrasound of Hepatic and System Hemodynamics in Patients with Alcoholic Liver Cirrhosis

    Microsoft Academic Search

    Zekanovic Drazen; Ljubicic Neven; Boban Marko; Nikolic Marko; Delic-Brkljacic Diana; Gacina Petar; Klarin Ivo; Turcinov Jadranko

    2010-01-01

    Objective The progression of liver cirrhosis eventually increases cardiac output, while blood pressure and systemic vascular resistance\\u000a are reduced. A complex behavior of portal hemodynamic to hepatic artery and system circulation has not yet been presented.\\u000a There is a lack in knowledge about the correlation of local and systemic circulation parameters to the degree of liver failure,\\u000a with respect to

  1. Potent antiviral therapy improves survival in acute on chronic liver failure due to hepatitis B virus reactivation

    PubMed Central

    Philips, Cyriac Abby; Sarin, Shiv Kumar

    2014-01-01

    Acute on chronic liver failure (ACLF) is a disease entity with a high mortality rate. The acute event arises from drugs and toxins, viral infections, bacterial sepsis, interventions (both surgical and non-surgical) and vascular events on top of a known or occult chronic liver disease. ACLF secondary to reactivation of chronic hepatitis B virus is a distinct condition; the high mortality of which can be managed in the wake of new potent antiviral therapy. For example, lamivudine and entecavir use has shown definite short-term survival benefits, even though drug resistance is a concern in the former. The renoprotective effects of telbivudine have been shown in a few studies to be useful in the presence of renal dysfunction. Monotherapy with newer agents such as tenofovir and a combination of nucleos(t)ides is promising for improving survival in this special group of liver disease patients. This review describes the current status of potent antiviral therapy in patient with acute on chronic liver failure due to reactivation of chronic hepatitis B, thereby providing an algorithm in management of such patients. PMID:25473156

  2. The Cytotoxic T Lymphocyte Response to Multiple Hepatitis B Virus Polymerase Epitopes During and After Acute Viral Hepatitis

    Microsoft Academic Search

    Barbara Rehermann; Patricia Fowler; John Sidney; Allan Redeker; Michael Brown; Bernard Moss; Francis V. Chisari

    1995-01-01

    Summary Cytotoxic T lymphocytes (CTL) are thought to contribute to viral clearance and liver cell injury during hepatitis B virus (HBV) infection. Using a strategy involving the in vitro stimulation of peripheral blood mononuclear cells (PBMC) with HBV-derived synthetic peptides containing HLA-A2.1, -A31, and -Aw68 binding motifs, we have previously described CTL responses to several epitopes within the HBV nudeocapsid

  3. Diagnosis of alcoholic cirrhosis with the right-to-left hepatic lobe ratio: concise communication

    SciTech Connect

    Shreiner, D.P.; Barlai-Kovach, M.

    1981-02-01

    Since scans of cirrhotic livers commonly show a reduction in size and colloid uptake of the right lobe, a quantitative measure of uptake was made using a minicomputer to determine total counts in regions of interest defined over each lobe. Right-to-left ratios were then compared in 103 patients. For normal paitents the mean ratio +- 1 s.d. was 2.85 +- 0.65, and the mean for patients with known cirrhosis was 1.08 +- 0.33. Patients with other liver diseases had ratios similar to the normal group. The normal range of the right-to-left lobe ratio was 1.55 to 4.15. The sensitivity of the ratio for alcoholic cirrhosis was 85.7% and the specificity was 100% in this patient population. The right-to-left lobe ratio was more sensitive and specific for alcoholic cirrhosis than any other criterion tested. An hypothesis is described to explain these results.

  4. Serum Hepatic Enzyme Activity and Alcohol Drinking Status in Relation to the Prevalence of Metabolic Syndrome in the General Japanese Population

    PubMed Central

    Uemura, Hirokazu; Katsuura-Kamano, Sakurako; Yamaguchi, Miwa; Sawachika, Fusakazu; Arisawa, Kokichi

    2014-01-01

    Background Studies on the combined associations of elevated serum hepatic enzyme activity and alcohol drinking with metabolic syndrome are rare. Our objectives were to evaluate the associations of elevated serum hepatic enzyme activity with the prevalence of metabolic syndrome in the general Japanese population and whether alcohol drinking had a modifying effect on these associations. Methods We conducted a cross-sectional study with 1,027 men and 1,152 women throughout Japan during 2002–2010. Biochemical factors including alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) were determined in overnight fasting blood, and a survey on lifestyle was conducted by questionnaire. Serum ALT and GGT levels were divided into tertiles in men and women, and their associations with the prevalence of metabolic syndrome were evaluated by logistic regressions. Results Elevated serum ALT and GGT, even within the reference range, were independently associated with increased metabolic syndrome prevalence and were associated with most of its components in both sexes, except for the association between GGT and low high-density lipoprotein (HDL) cholesterol in men. Stratified analyses by alcohol drinking status revealed that within the same tertile category of serum ALT and GGT, subjects classified as alcohol abstainers showed higher adjusted odds ratios for metabolic syndrome prevalence than those classified as regular alcohol drinkers in both sexes. The interaction effects of serum GGT with alcohol drinking status on metabolic syndrome prevalence were significant in both sexes. Conclusions These results suggest that elevated serum ALT and GGT, even within the reference range, are independently associated with increased metabolic syndrome prevalence, especially in alcohol abstainers, in Japanese men and women. PMID:24755715

  5. 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

  6. Inhibition of diethylnitrosamine-initiated alcohol-promoted hepatic inflammation and precancerous lesions by flavonoid luteolin is associated with increased sirtuin 1 activity in mice

    PubMed Central

    Rafacho, Bruna Paola Murino; Stice, Camilla Peach; Liu, Chun; Greenberg, Andrew S.; Ausman, Lynne M.

    2015-01-01

    Background Chronic and excessive alcohol consumption is an established risk for hepatic inflammation and carcinogenesis. Luteolin is one of the most common flavonoids present in plants and has potential beneficial effects against cancer. In this study, we examined the effect and potential mechanisms of luteolin supplementation in a carcinogen initiated alcohol-promoted pre-neoplastic liver lesion mouse model. Methods C57BL/6 mice were injected with diethylnitrosamine (DEN) [i.p. 25 mg/kg of body weight (BW)] at 14 days of age. At 8 weeks of age mice were group pair-fed with Lieber-DeCarli liquid control diet or alcoholic diet [ethanol (EtOH) diet, 27% total energy from ethanol] and supplemented with a dose of 30 mg luteolin/kg BW per day for 21 days. Results DEN-injected mice fed EtOH diet displayed a significant induction of pre-neoplastic lesions, a marker associated with presence of steatosis and inflammation. Dietary luteolin significantly reduced the severity and incidence of hepatic inflammatory foci and steatosis in DEN-injected mice fed EtOH diet, as well the presence of preneoplastic lesions. There was no difference on hepatic protein levels of sirtuin 1 (SIRT1) among all groups; however, luteolin supplementation significantly reversed alcohol-reduced SIRT1 activity assessed by the ratio of acetylated and total forkhead box protein O1 (FoXO1) and SIRT1 target proliferator-activated receptor gamma, coactivator 1 alpha (PGC1?). Conclusions Dietary intake of luteolin prevents alcohol promoted pre-neoplastic lesions, potentially mediated by SIRT1 signaling pathway. PMID:26005679

  7. Therapeutic Role of Ursolic Acid on Ameliorating Hepatic Steatosis and Improving Metabolic Disorders in High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Rats

    PubMed Central

    Meng, Fanyu; Wang, Yemei; Sun, Zongxiang; Guo, Fuchuan; Li, Xiaoxia; Meng, Man; Li, Ying; Sun, Changhao

    2014-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases around the world, and is closely associated with obesity, diabetes, and insulin resistance. Ursolic acid (UA), an ubiquitous triterpenoid with multifold biological roles, is distributed in various plants. This study was conducted to investigate the therapeutic effect and potential mechanisms of UA against hepatic steatosis in a high-fat diet (HFD)-induced obese non-alcoholic fatty liver disease (NAFLD) rat model. Methodology/Principal Findings Obese NAFLD model was established in Sprague-Dawley rats by 8-week HFD feeding. Therapeutic role of UA was evaluated using 0.125%, 0.25%, 0.5% UA-supplemented diet for another 6 weeks. The results from both morphologic and histological detections indicated that UA significantly reversed HFD-induced hepatic steatosis and liver injury. Besides, hepatic peroxisome proliferator-activated receptor (PPAR)-? was markedly up-regulated at both mRNA and protein levels by UA. Knocking down PPAR-? significantly inhibited the anti-steatosis role of UA in vitro. HFD-induced adverse changes in the key genes, which participated in hepatic lipid metabolism, were also alleviated by UA treatment. Furthermore, UA significantly ameliorated HFD-induced metabolic disorders, including insulin resistance, inflammation and oxidative stress. Conclusions/Significance These results demonstrated that UA effectively ameliorated HFD-induced hepatic steatosis through a PPAR-? involved pathway, via improving key enzymes in the controlling of lipids metabolism. The metabolic disorders were accordingly improved with the decrease of hepatic steatosis. Thereby, UA could be a promising candidate for the treatment of NAFLD. PMID:24489777

  8. Liver Regeneration Signature in Hepatitis B Virus (HBV)-Associated Acute Liver Failure Identified by Gene Expression Profiling

    PubMed Central

    Diaz, Giacomo; Kleiner, David E.; Tice, Ashley; Fantola, Giovanni; Zamboni, Fausto; Mishra, Lopa; Farci, Patrizia

    2012-01-01

    Introduction The liver has inherent regenerative capacity via mitotic division of mature hepatocytes or, when the hepatic loss is massive or hepatocyte proliferation is impaired, through activation of hepatic stem/progenitor cells (HSPC). The dramatic clinical course of acute liver failure (ALF) has posed major limitations to investigating the molecular mechanisms of liver regeneration and the role of HSPC in this setting. We investigated the molecular mechanisms of liver regeneration in 4 patients who underwent liver transplantation for hepatitis B virus (HBV)-associated ALF. Methods and Findings Gene expression profiling of 17 liver specimens from the 4 ALF cases and individual specimens from 10 liver donors documented a distinct gene signature for ALF. However, unsupervised multidimensional scaling and hierarchical clustering identified two clusters of ALF that segregated according to histopathological severity massive hepatic necrosis (MHN; 2 patients) and submassive hepatic necrosis (SHN; 2 patients). We found that ALF is characterized by a strong HSPC gene signature, along with ductular reaction, both of which are more prominent in MHN. Interestingly, no evidence of further lineage differentiation was seen in MHN, whereas in SHN we detected cells with hepatocyte-like morphology. Strikingly, ALF was associated with a strong tumorigenesis gene signature. MHN had the greatest upregulation of stem cell genes (EpCAM, CK19, CK7), whereas the most up-regulated genes in SHN were related to cellular growth and proliferation. The extent of liver necrosis correlated with an overriding fibrogenesis gene signature, reflecting the wound-healing process. Conclusion Our data provide evidence for a distinct gene signature in HBV-associated ALF whose intensity is directly correlated with the histopathological severity. HSPC activation and fibrogenesis positively correlated with the extent of liver necrosis. Moreover, we detected a tumorigenesis gene signature in ALF, emphasizing the close relationship between liver regeneration and liver cancer. PMID:23185381

  9. IL-22 modulates gut epithelial and immune barrier functions following acute alcohol exposure and burn injury

    PubMed Central

    Rendon, Juan L.; Li, Xiaoling; Akhtar, Suhail; Choudhry, Mashkoor A.

    2012-01-01

    Interleukin (IL)–22 maintains gut epithelial integrity and expression of antimicrobial peptides (AMPs) Reg3? and Reg3?. Our laboratory has shown that acute alcohol/ethanol (EtOH) exposure prior to burn injury results in increased gut permeability, intestinal T cell suppression and enhanced bacterial translocation. Herein, we determined the effect of combined EtOH intoxication and burn injury on intestinal levels of IL-22 as well as Reg3? and Reg3? expression. We further examined whether in vivo restitution of IL-22 restores gut permeability, Reg3? and Reg3? levels, and bacterial load (e.g. gut bacterial growth) within the intestine following EtOH and burn injury. Male mice, ~25g, were gavaged with EtOH (2.9 mg/kg) prior to receiving a ~12.5% total body surface area full thickness burn. Mice were immediately treated with saline control or IL-22 (1 mg/kg) by i.p. injection. One day post injury, there was a significant decrease in intestinal IL-22, Reg3? and Reg3? expression along with an increase in intestinal permeability and gut bacterial load following EtOH combined with burn injury, as compared to sham injury. Treatment with IL-22 normalized Reg3? and Reg3? expression, and attenuated the increase in intestinal permeability following EtOH and burn injury. Qualitatively, IL-22 treatment reduced the bacterial load in nearly half of mice receiving EtOH combined with burn injury. Our data indicate that IL-22 maintains gut epithelial and immune barrier integrity following EtOH and burn injury; thus, the IL-22/AMP pathway may provide a therapeutic target for the treatment of patients who sustain burn injury under the influence of EtOH. PMID:23143063

  10. Case-Reporting of Acute Hepatitis B and C Among Injection Drug Users

    Microsoft Academic Search

    Holly Hagan; Nadine Snyder; Eileen Hough; Tianji Yu; Shelly McKeirnan; Janice Boase; Jeffrey Duchin

    Although public health surveillance system data are widely used to describe the epidemiology of communicable disease, occurrence of hepatitis B and C virus (HBV and HCV, respectively) infections may be misrepresented by under-reporting in injection drug users (IDUs). This study was carried out to examine the relationship between HBV and HCV incidence and case-reporting of hepatitis B and C in

  11. Capacity of a natural strain of woodchuck hepatitis virus, WHVNY, to induce acute infection in naive adult woodchucks.

    PubMed

    Freitas, Natalia; Lukash, Tetyana; Dudek, Megan; Litwin, Sam; Menne, Stephan; Gudima, Severin O

    2015-07-01

    Woodchuck hepatitis virus (WHV) is often used as surrogate to study mechanism of HBV infection. Currently, most infections are conducted using strains WHV7 or WHV8 that have very high sequence identity. This study focused on natural strain WHVNY that is more genetically distant from WHV7. Three naive adult woodchucks inoculated with WHVNY developed productive acute infection with long lasting viremia. However, only one of two woodchucks infected with WHV7 at the same multiplicity demonstrated productive liver infection. Quantification of intracellular WHV RNA and DNA replication intermediates; percentages of core antigen-positive hepatocytes; and serum relaxed circular DNA showed that strains WHVNY and WHV7 displayed comparable replication levels and capacities to induce acute infection in naive adult woodchucks. Strain WHVNY was therefore validated as valuable reagent to analyze the mechanism of hepadnavirus infection, especially in co- and super-infection settings, which required discrimination between two related virus genomes replicating in the same liver. PMID:25979221

  12. Sleep Architecture in Adolescent Marijuana and Alcohol Users during Acute and Extended Abstinence

    PubMed Central

    Cohen-Zion, Mairav; Drummond, Sean P.A.; Padula, Claudia B.; Winward, Jennifer; Kanady, Jennifer; Medina, Krista L.; Tapert, Susan F.

    2009-01-01

    This study examined sleep changes following cessation of marijuana and alcohol use during late adolescence. Twenty-nine heavy marijuana and alcohol users and 20 matched controls were studied during a 28-day monitored abstinence period. Sleep as examined as a function of prior substance use during Nights 1–2 and Nights 27–28. On Night 2, percent Rapid Eye Movement sleep was predicted by past month alcohol use, whereas percent Slow Wave Sleep was predicted by marijuana intake. By Night 28, neither alcohol no marijuana use predicted any sleep architecture measure. However, on Night 28, indices of period limb movements (PLMs) in sleep were predicted by marijuana and alcohol intake. Results indicate that in adolescents: (1) cessation of heavy marijuana and alcohol use may influence sleep; (2) most sleep abnormalities abate within several weeks of abstinence; and (3) PLMs may increase following abstinence. PMID:19505769

  13. Animal models for studying hepatitis C and alcohol effects on liver

    PubMed Central

    Mercer, David F

    2011-01-01

    Chronic consumption of ethanol has a dramatic effect on the clinical outcome of patients with hepatitis C virus (HCV) infection, but the mechanism linking these two pathologies is unknown. Presently, in vitro systems are limited in their ability to study the interaction between a productive wild-type HCV infection and chronic ethanol exposure. Mouse models are potentially very useful in dissecting elements of the HCV-ethanol relationship. Experiments in mice that transgenically express HCV proteins are outlined, as are experiments for the generation of mice with chimeric human livers. The latter models appear to have the most promise for accurately modeling the effects of chronic ethanol intake in HCV-infected human livers. PMID:21633656

  14. Acute Interaction of Baclofen in Combination with Alcohol in Heavy Social Drinkers

    PubMed Central

    Evans, Suzette M.; Bisaga, Adam

    2008-01-01

    Background There is growing evidence that GABA-B receptor agonists may be effective in the treatment of alcohol abuse or dependence. The primary goal of this study was to determine the safety of baclofen in combination with alcohol consumption in heavy drinkers. In addition, the effects of baclofen alone, and in combination with alcohol, on subjective effects, cognitive performance effects, as well as alcohol craving, were assessed. Methods Eighteen non-treatment seeking heavy social drinkers (mean of 28 drinks/week) who did not meet criteria for alcohol dependence participated. All individuals were tested using a double-blind double-dummy design with six 2-day inpatient phases. Baclofen (0, 40, and 80 mg) was administered 2.5 hours before alcohol (1.5 g/l body water or approximately 0.75 g/kg) or placebo beverages, given in 4 divided doses every 20 min. Results Baclofen, either alone, or in combination with alcohol, produced only modest increases in heart rate and blood pressure and no adverse effects were reported. Baclofen did not increase positive subjective effects (e.g., Stimulant effects, Drug Liking) but did increase sedation and impair performance. Even though both baclofen and alcohol impaired performance, for the most part performance was not impaired to a greater extent when baclofen was combined with alcohol. Among this population of non-dependent drinkers, baclofen did not alter alcohol craving or alcohol-induced positive subjective effects. Conclusions Baclofen alone has minimal abuse liability in heavy social drinkers and baclofen is relatively well tolerated and safe when given in combination with intoxicating doses of alcohol. PMID:18840257

  15. A case of acute hepatic insufficiency treated with novel plasmapheresis plasma diafiltration for bridge use until liver transplantation.

    PubMed

    Mori, Tsuyoshi; Eguchi, Yutaka; Shimizu, Tomoharu; Endo, Yoshihiro; Yoshioka, Toyokazu; Hanasawa, Kazuyoshi; Tani, Tohru

    2002-12-01

    A patient with acute hepatic insufficiency induced by a drug presented to our institution, and we performed a novel plasmapheresis that we call plasma dia-filtration (PDF). The patient was a 36 year old woman. She underwent 11 sessions of PDF for a duration of about 9 h for each procedure using the Evacure EC-2A filter together with 20 units of fresh frozen plasma and dialysate simultaneously. Serum levels of total bilirubin and prothrombin time were significantly improved after she underwent each procedure. However, after the third procedure the levels returned to the same level as on the previous day. Encephalopathy improved after the first procedure, and this improvement was maintained until the ninth procedure. The patient prepared to undergo liver transplantation after the tenth procedure because of the development of hepatic coma, but she died of respiratory insufficiency before undergoing the procedure. Accordingly in this case, PDF worked to maintain liver function in acute liver failure and may act as bridge therapy until the patient can undergo liver transplantation. PMID:12460412

  16. Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in Mice.

    PubMed

    Hao, Lijun; Xie, Yuxi; Wu, Guikai; Cheng, Aibin; Liu, Xiaogang; Zheng, Rongjuan; Huo, Hong; Zhang, Junwei

    2015-01-01

    We investigated the effects of Hericium erinaceus (HEM) on liver injury induced by acute alcohol administration in mice. Mice received ethanol (5?g/kg?BW) by gavage every 12?hrs for a total of 3 doses. HEM (200?mg/kg?BW) was gavage before ethanol administration. Subsequent serum alanine aminotransferase (ALT) level, aspartate aminotransaminase (AST) level, Maleic dialdehyde (MDA) level, hepatic total antioxidant status (TAOS), and activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) were determined by ELISA and immunohistochemistry, respectively. HEM administration markedly (P < 0.05) decreased serum ALT, AST, and MDA levels. The hepatic histopathological observations showed that HEM had a relatively significant role in mice model, which had alcoholic liver damage. In conclusion, we observed that HEM (200?mg/kg?BW) supplementation could restrain the hepatic damage caused by acute alcohol exposure. PMID:25960751

  17. Treatment of severe, nonfulminant acute hepatitis B with lamivudine vs placebo: a prospective randomized double-blinded multicentre trial.

    PubMed

    Wiegand, J; Wedemeyer, H; Franke, A; Rößler, S; Zeuzem, S; Teuber, G; Wächtler, M; Römmele, U; Ruf, B; Spengler, U; Trautwein, C; Bock, C T; Fiedler, G M; Thiery, J; Manns, M P; Brosteanu, O; Tillmann, H L

    2014-10-01

    Acute hepatitis B virus (aHBV) infection can lead to fulminant liver failure, which likely is prevented by early lamivudine therapy. Even nonfulminant but severe acute hepatitis B can lead to significant morbidity and impaired quality of life. Therefore, lamivudine was evaluated in patients with severe aHBV in a placebo-controlled trial. Patients with severe aHBV infection (ALT >10× ULN, bilirubin >85 ?m, prothrombin time >50%) were prospectively treated with lamivudine 100 mg/day or with placebo within 8 days after the diagnosis. The primary end point was time to bilirubin <34.2 ?m. Secondary end points were time to clear HBsAg and HBV-DNA, development of anti-HBs and normalization of ALT. Eighteen cases were randomized to lamivudine, 17 to placebo. 94% of patients were hospitalized. No individual progressed to hepatic failure; all but one patient achieved the primary end point. Due to smaller than expected patient numbers, all study end points did not become statistically significant between treatment arms. Median time end points [in days] were bilirubin <34.2 ?m (26.5 vs 32), ALT normalization (35 vs 48) and HBsAg clearance (48 vs 67) referring to earlier recovery under lamivudine, in contrast to loss of HBV-DNA (62 vs 54) and development of anti-HBs (119 vs 109). In all but two patients (one in every group), HBsAg clearance was reached in the study. Adverse events occurred more frequently during lamivudine therapy, but did not reach statistical significance. Lamivudine may ameliorate severe aHBV infection, but limited patient numbers prevented definite conclusions. PMID:24329913

  18. High Level of PD1 Expression on Hepatitis C Virus (HCV)Specific CD8+ and CD4+ T Cells during Acute HCV Infection, Irrespective of Clinical Outcome

    Microsoft Academic Search

    Victoria Kasprowicz; J. Schulze zur Wiesch; Thomas Kuntzen; Brian E. Nolan; Steven Longworth; Andrew Berical; Jenna Blum; Cory McMahon; Laura L. Reyor; Nahel Elias; William W. Kwok; Barbara G. McGovern; Gordon Freeman; Raymond T. Chung; Paul Klenerman; Lia Lewis-Ximenez; Bruce D. Walker; Todd M. Allen; Arthur Y. Kim; Georg M. Lauer

    2008-01-01

    We monitored expression of PD-1 (a mediator of T-cell exhaustion and viral persistence) on hepatitis C virus (HCV)-specific CD8 and CD4 T cells from blood and liver during acute and chronic infections and after the resolved infection stage. PD-1 expression on HCV-specific T cells was high early in acute infection irrespective of clinical outcome, and most cells continued to express

  19. Acute effect of altered tryptophan levels and alcohol on aggression in normal human males

    Microsoft Academic Search

    Robert O. Pihl; Simon N. Young; Philip Harden; Stewart Plotnick; Brian Chamberlain; Frank R. Ervin

    1995-01-01

    Normal males received amino acid mixtures designed to raise or lower tryptophan availability, and thus to raise or lower brain serotonin synthesis. They also received alcoholic or non-alcoholic drinks. The subjects were tested in the Taylor Competitive Reaction Time Task in which they competed against a (non-existent) partner in a reaction time task. The magnitude of electric shocks that the

  20. Pathophysiological Similarities and Synergisms in Alcoholic and Non-Alcoholic Steatohepatitis

    Microsoft Academic Search

    Claus Hellerbrand

    2010-01-01

    Chronic alcohol consumption is one of the main etiological factors for liver disease worldwide, however only a fraction of drinkers develop significant hepatic inflammation (alcoholic steatohepatitis), and even less progress to significant hepatic fibrosis and cirrhosis. The pathophysiological significance of hepatic lipid accumulation in the absence of significant alcohol consumption is also increasingly recognized. Non-alcoholic fatty liver disease (NAFLD) is

  1. Intestinal plethora: An early sign of acute posttraumatic hepatic artery-portal vein arteriovenous fistula

    Microsoft Academic Search

    Salvatore J. A. Sclafani; Michael Herskowitz; Susan Rachlin

    1995-01-01

    Traumatic communications between the hepatic artery or its branches and the portal vein or its tributaries usually are clinically\\u000a occult until the late sequelae of portal hypertension, such as esophageal and mesenteric varices, ascites, or congestive heart\\u000a failure, become manifest. The authors describe the early diagnosis of such a lesion by computed tomography. The CT findings\\u000a included a hepatic hematoma

  2. Case-reporting of acute hepatitis B and C among injection drug users

    Microsoft Academic Search

    Holly Hagan; Nadine Snyder; Eillen Hough; Tianji Yu; Shelly McKeirnan; Janice Boase; Jeffrey Duchin

    2002-01-01

    Although public health surveillance system data are widely used to describe the epidemiology of communicable disease, occurrence\\u000a of hepatitis B and C virus (HBV and HCV, respectively) infections may be misrepresented by under-reporting in injection drug\\u000a users (IDUs). This study was carried out to examine the relationship between HBV and HCV incidence and case-reporting of hepatitis\\u000a B and C in

  3. Epidemiology of acute and chronic hepatitis B virus infection in Norway, 1992-2009

    Microsoft Academic Search

    Gražina Rimšelien?; Øivind Nilsen; Hilde Kløvstad; Hans Blystad; Preben Aavitsland

    2011-01-01

    Background  Norway is classified as a low prevalence country for hepatitis B virus infection. Vaccination is only recommended for risk\\u000a groups (intravenous drug users (IDUs), Men who have Sex with Men (MSM), immigrants and contacts of known carriers). We describe\\u000a the epidemiology of reported cases of hepatitis B in Norway, during the years 1992-2009 in order to assess the validity of

  4. Effects of Combined Alcohol and Anti-HIV Drugs on Cellular Stress Responses in Primary Hepatocytes and Hepatic Stellate and Kupffer Cells

    PubMed Central

    Hu, Jay; Han, Hui; Lau, Mo Yin; Lee, Harrison; MacVeigh-Aloni, Michelle; Ji, Cheng

    2015-01-01

    Background Certain anti-HIV drugs alone or in combination are often associated with liver damages, which are frequently worsened by alcohol consumption. We previously found an endoplasmic reticulum (ER) stress mechanism for the drug- and alcohol-induced hepatic injuries in animal models and in vitro hepatocytes. However, it is unknown whether anti-HIV drugs and alcohol induce similar cellular stress responses and injuries in liver nonparenchymal cells. Methods Primary mouse hepatocytes (PMH), kupffer cells (KC), and hepatocellular stellate cells (HSC) were freshly isolated from mouse liver and treated with DMSO, stress-inducing pharmaceutical agents, alcohol alone, or in combination with antiviral ritonavir (RIT), lopinavir (LOP), or efavirenz (EFV). Expression of cellular stress markers, protein colocalization, and cell death were analyzed with immunoblotting, immunocytochemistry, and positive double staining with Sytox green and Hoechst blue, respectively. Results Expression of the ER stress markers of BiP, CHOP, and SERCA and the autophagy marker LC3 was significantly changed in PMH in response to combined alcohol, RIT, and LOP, which was companied by increased cell death compared with control. In contrast, although pharmaceutical agents induced ER stress and cell death, no significant ER stress or cell death was found in KC treated with alcohol, RIT, LOP, and EFV singly or in combination. In HSC, alcohol, RIT, LOP, or EFV induced BiP, but not CHOP, SERCA, or cell death compared with vehicle control. Further in PMH, RIT and LOP or in combination with alcohol-induced dose-dependent inhibition of ?-actin. Inhibition of ?-actin by RIT and LOP was companied with an inhibited nuclear expression of the antioxidant response regulator Nrf2 and reduced GST downstream of Nrf2. Ascorbic acid treatment reduced the alcohol-, RIT-, and LOP-induced cell death. Conclusions The data suggest for the first time that sensitivities of hepatocytes and nonparenchymal cells to alcohol and anti-HIV drugs in vitro are different in terms of cellular stress response and cell death injury. Oxidative stress mediated by Nrf2 contributes to the alcohol- and drug-induced toxicity in the hepatocytes. PMID:25623401

  5. Estimating Alcohol Consumption

    Microsoft Academic Search

    Jonathan Chick; Esko Kemppainen

    2007-01-01

    Alcohol use is one of the two main aetiologies of acute pancreatitis. Detection of excessive alcohol consumption is problematic, illustrated by the fact that self-reports of alcohol consumption account for only approximately 50% of the reported sales of alcohol. To improve the reliability, structured questionnaires and various biochemical markers have been developed to estimate alcohol consumption objectively. Further, the pattern

  6. 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

  7. Analysis of HBV genotype, drug resistant mutations, and pre-core/basal core promoter mutations in Korean patients with acute hepatitis B.

    PubMed

    Lee, Jong Ho; Hong, Sun Pyo; Jang, Eun Sun; Park, Sang Jong; Hwang, Seong Gyu; Kang, Sook-Kyoung; Jeong, Sook-Hyang

    2015-06-01

    Acute hepatitis B, caused by hepatitis B virus (HBV) strains with drug resistant mutations or pre-core/basal core promoter (PC/BCP) mutations, is a public health concern, because this infection is often associated with poor disease outcome or difficulty in therapeutic choice. The HBV genotype, the prevalence of drug resistant mutations, and PC/BCP mutations in Korean patients with acute hepatitis B were studied. From 2006 to 2008, 36 patients with acute hepatitis B were enrolled prospectively in four general hospitals. Among them, 20 showed detectable HBV DNA (median value was 4.8 log copies/mL). HBV genotyping and analysis of HBV mutations that conferred resistance against lamivudine, adefovir, or entecavir and of PC/BCP mutations were performed using highly sensitive restriction fragment mass polymorphism (RFMP) analysis. All 20 patients were infected with HBV genotype C, which causes almost all cases of chronic hepatitis B in Korea. No patient showed mutations that conferred resistance against lamivudine (L180M, M204V/I), adefovir (A181T, N236S), or entecavir (I169M, A184T/V, S202I/G, M250V/I/L). However, four patients had BCP mutations, and two had PC mutations. Platelet counts were significantly lower in the four patients with PC/BCP mutations compared to those with wild type. In this study, all acute hepatitis B patients had genotype C HBV strains with no drug resistant mutations. However, 20% showed PC/BCP mutations. This highlights the need for further study on the significance of PC/BCP mutations. J. Med. Virol. 87:993-998, 2015. © 2015 Wiley Periodicals, Inc. PMID:25712861

  8. Initial load of hepatitis B virus (HBV), its changing profile, and precore\\/core promoter mutations correlate with the severity and outcome of acute HBV infection

    Microsoft Academic Search

    Shigehiko Sainokami; Koichi Abe; Akihiro Sato; Ryujin Endo; Yasuhiro Takikawa; Kazuyuki Suzuki; Hiroaki Okamoto

    2007-01-01

    Background  The pathogenesis of the fulminant or severe form of acute hepatitis B virus (HBV) infection remains unclear, although both\\u000a host- and virus-specific factors are considered to have a great impact on the c course. We aimed to define possible viral\\u000a factors implicated in the severe form of acute HBV infection.\\u000a \\u000a \\u000a \\u000a Methods  We investigated viral factors in 42 patients with acute HBV

  9. Sleep architecture in adolescent marijuana and alcohol users during acute and extended abstinence

    Microsoft Academic Search

    Mairav Cohen-Zion; Sean P. A. Drummond; Claudia B. Padula; Jennifer Winward; Jennifer Kanady; Krista L. Medina; Susan F. Tapert

    2009-01-01

    This study examined sleep changes following cessation of marijuana and alcohol use during late adolescence. Twenty-nine heavy marijuana and alcohol users and 20 matched controls were studied during a 28-day monitored abstinence period. Sleep was examined as a function of prior substance use during Nights 1–2 and Nights 27–28. On Night 2, percent rapid eye movement sleep was predicted by

  10. Childhood Sexual Abuse and Acute Alcohol Effects on Men’s Sexual Aggression Intentions

    PubMed Central

    Davis, Kelly Cue; Schraufnagel, Trevor J.; Jacques-Tiura, Angela J.; Norris, Jeanette; George, William H.; Kiekel, Preston A.

    2012-01-01

    Objective Although research has established childhood sexual abuse (CSA) as a risk factor for men’s perpetration of sexual aggression, there has been little investigation of the factors undergirding this association. This study represents one of the first to use a laboratory-based sexual aggression analogue coupled with an alcohol administration protocol to investigate the pathways through which CSA and alcohol influence men’s self-reported sexual aggression intentions. Method After completing background questionnaires, male social drinkers (N = 220) were randomly assigned to a control, placebo, low alcohol dose or high alcohol dose condition. Following beverage consumption, participants read a sexual scenario in which the female partner refused to have unprotected sexual intercourse, after which they completed dependent measures. Results Path analysis indicated that men with a CSA history and intoxicated men perceived the female character as more sexually aroused and reported stronger sexual entitlement cognitions, both of which were in turn associated with greater condom use resistance and higher sexual aggression intentions. Exploratory analyses revealed that intoxication moderated the effects of CSA history on sexual entitlement cognitions, such that sexual entitlement cognitions were highest for men who had a CSA history and consumed alcohol. Conclusions Findings suggest that CSA history may facilitate sexual assault perpetration through its effects on in-the-moment cognitions, and that these effects may be exacerbated by alcohol intoxication. PMID:22754720

  11. Ethanol Extract of Fructus Schisandrae Decreases Hepatic Triglyceride Level in Mice Fed with a High Fat/Cholesterol Diet, with Attention to Acute Toxicity

    PubMed Central

    Pan, Si-Yuan; Yu, Zhi-Ling; Dong, Hang; Xiang, Chun-Jing; Fong, Wang-Fun; Ko, Kam-Ming

    2011-01-01

    Effects of the ethanol extract of Fructus Schisandrae (EtFSC) on serum and liver lipid contents were investigated in mice fed with high fat/cholesterol (HFC) diet for 8 or 15 days. The induction of hypercholesterolemia by HFC diet caused significant increases in serum and hepatic total cholesterol (TC) levels (up to 62% and 165%, resp.) and hepatic triglyceride (TG) levels (up to 528%) in mice. EtFSC treatment (1 or 5?g/kg/day for 7 days; from Day 1 to 7 or from Day 8 to 14, i.g.) significantly decreased the hepatic TG level (down to 35%) and slightly increased the hepatic index (by 8%) in hypercholesterolemic mice. Whereas fenofibrate treatment (0.1?g/kg/day for 7 days, i.g.) significantly lowered the hepatic TG level (by 61%), it elevated the hepatic index (by 77%) in hypercholesterolemic mice. Acute toxicity test showed that EtFSC was relatively non-toxic, with an LD50 value of 35.63 ± 6.46?g/kg in mice. The results indicate that EtFSC treatment can invariably decrease hepatic TG in hypercholesterolemic mice, as assessed by both preventive and therapeutic protocols, suggesting its potential use for fatty liver treatment. PMID:19592476

  12. Acute hepatitis B caused by a vaccine-escape HBV strain in vaccinated subject: sequence analysis and therapeutic strategy.

    PubMed

    Luongo, Monica; Critelli, Rosina; Grottola, Antonella; Gitto, Stefano; Bernabucci, Veronica; Bevini, Mirco; Vecchi, Chiara; Montagnani, Giuliano; Villa, Erica

    2015-01-01

    HBV vaccine contains the 'a' determinant region, the major immune-target of antibodies (anti-HBs). Failure of immunization may be caused by vaccine-induced or spontaneous 'a' determinant surface gene mutants. Here, we evaluate the possible lack of protection by HBV vaccine, describing the case of an acute hepatitis B diagnosed in a 55-year-old Caucasian male unpaid blood donor, vaccinated against HBV. Sequencing data for preS-S region revealed multiple point mutations. Of all the substitutions found, Q129H, located in the "a" determinant region of HBsAg, can alter antigenicity, leading to mutants. This mutant may cause vaccine failure especially when associated with high viremia of infecting source. PMID:25542480

  13. Incubation Phase of Acute Hepatitis B in Man: Dynamic of Cellular Immune Mechanisms

    Microsoft Academic Search

    George J. M. Webster; Stephanie Reignat; Mala K. Maini; Simon A. Whalley; Graham S. Ogg; Abigail King; David Brown; Peter L. Amlot; Roger Williams; Diego Vergani; Geoffrey M. Dusheiko; Antonio Bertoletti

    2000-01-01

    After hepatitis B virus (HBV) infection, liver injury and viral control have been thought to result from lysis of infected hepatocytes by virus-specific cytotoxic T cells. Patients are usually studied only after developing significant liver injury, and so the viral and immune events during the incubation phase of disease have not been defined. During a single-source outbreak of HBV infection,

  14. DNA Microarray Analysis of Chimpanzee Liver during Acute Resolving Hepatitis C Virus Infection

    Microsoft Academic Search

    CATHERINE B. BIGGER; KATHLEEN M. BRASKY; ROBERT E. LANFORD

    2001-01-01

    Hepatitis C virus (HCV) poses a worldwide health problem in that the majority of individuals exposed to HCV become chronically infected and are predisposed for developing significant liver disease. DNA microarray technology provides an opportunity to survey transcription modulation in the context of an infectious disease and is a particularly attractive approach in characterizing HCV-host interactions, since the mechanisms underlying

  15. Adaptive immune responses in acute and chronic hepatitis C virus infection

    Microsoft Academic Search

    David G. Bowen; Christopher M. Walker

    2005-01-01

    The hepatitis C virus (HCV) persists in the majority of infected individuals and is a significant cause of human illness and death globally. Recent studies have yielded important insights into immunity to HCV, in particular revealing the central role of T cells in viral control and clearance. Other key features of adaptive immune responses remain obscure, including mechanisms by which

  16. 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

  17. Risk factors for acute hepatitis A infection in Korea in 2007 and 2009: a case-control study.

    PubMed

    Seo, Joo Youn; Choi, Bo Youl; Ki, Moran; Jang, Hye Lim; Park, Hee Suk; Son, Hyun Jin; Bae, Si Hyun; Kang, Jin Han; Jun, Dae Won; Lee, Jin-Woo; Hong, Young Jin; Kim, Young Seok; Kim, Chang-Hwi; Chang, U Im; Kim, Jong-Hyun; Yang, Hyeon Woong; Kim, Hong Soo; Park, Kyeong Bae; Hwang, Jae Seok; Heo, Jeong; Kim, In Hee; Kim, Jung Soo; Cheon, Gab Jin

    2013-06-01

    This study aimed to identify the risk factors associated with acute hepatitis A virus (HAV) infection in the Korean population. Participants were recruited from five referral hospitals across the country in 2007 and from 11 hospitals in 2009. Patients with positive anti-HAV IgM antibody tests became the case group, while patients treated for non-contagious diseases at the same hospitals were recruited as controls. A total of 222 and 548 case-control pairs were studied in the 2007 and 2009 surveys, respectively. Data from the surveys were analyzed jointly. In a multivariate analysis, sharing the household with HAV-infected family members (OR, 6.32; 95% CI, 1.4-29.6), contact with other HAV-infected individuals (OR, 4.73; 95% CI, 2.4-9.4), overseas travel in 2007 (OR, 19.93; 95% CI, 2.3-174.4), consumption of raw shellfish (OR, 2.51; 95% CI, 1.8-3.5), drinking bottled water (OR, 1.64; 95% CI, 1.3-8.4), and occupation that involve handling food (OR, 3.30; 95% CI, 1.3-8.4) increased the risk of HAV infection. Avoiding contact with HAV-infected individuals and avoiding raw foods eating could help minimize the risk of hepatitis A infection. Immunization must be beneficial to individuals who handle food ingredients occupationally or travel overseas to HAV-endemic areas. PMID:23772157

  18. Study on protecting effects of Baicalin and Octreotide on hepatic injury in rats with severe acute pancreatitis

    PubMed Central

    Zhang, Xi-Ping; Zhang, Jie; Ren, Zheng; Feng, Guang-Hua; Zhu, Wei; Cai, Yang; Yang, Qi-Jun; Ju, Tong-Fa; Xie, Qi; Yuan, Wen-Qin

    2008-01-01

    AIM: To investigate the protective effects and mechanisms of Baicalin and Octreotide on hepatic injury in rats with severe acute pancreatitis (SAP). METHODS: The SAP rat models were prepared and randomly assigned to the model control group, Baicalin treated group, and Octreotide treated group while other healthy rats were assigned to the sham-operated group. Rat mortality, levels of ALT, AST, liver and pancreas pathological changes in all groups were observed at 3, 6 and 12 h after operation. Tissue microarray (TMA) sections of hepatic tissue were prepared to observe expression levels of Bax, Bcl-2 protein and Caspase-3, and changes of apoptotic indexes. RESULTS: Rat survival at 12 h, expression levels of Bax, Caspase-3 protein and apoptotic indexes of liver were all significantly higher in treated groups than in model control group. While the liver and pancreas pathological scores, contents of ALT, AST, and expression levels of Bcl-2 protein were all lower in treated groups than in the model control group. CONCLUSION: Both Baicalin and Octreotide can protect rats with SAP by decreasing the contents of ALT, AST and expression levels of Bcl-2 protein, and improving the expression levels of Bax protein, Caspase-3 protein, and inducing apoptosis. PMID:19030211

  19. Toxic myopathy and acute hepatic necrosis in cattle caused by ingestion of Senna obtusifolia (sicklepod; coffee senna) in Brazil.

    PubMed

    Furlan, Fernando Henrique; Zanata, Carina; Damasceno, Everson Dos Santos; de Oliveira, Leonardo Pintar; da Silva, Leilane Aparecida; Colodel, Edson Moleta; Riet-Correa, Franklin

    2014-12-15

    The epidemiological, clinical and pathological findings of field and experimental Senna obtusifolia (sicklepod; coffee senna) poisoning in cattle are described. The low availability of good quality forage and high rate of infestation of pastures by S. obtusifolia were the factors that led to poisonous plant ingestion. In this study, the morbidity ranged between 2% and 27.9%, and the lethality was 100%. For the experimental study, six cattle were fed with the aerial parts of S. obtusifolia collected in three different seasons at 9%-38% of the animal's body weight. The experimental and field diseases were similar. The main clinical signs were diarrhea, reluctance to move, muscular weakness and recumbency. The gross findings included pale discoloration of the skeletal muscle. Microscopically, the affected cattle showed degeneration and necrosis of the skeletal muscles and occasionally of the cardiac muscles. Additionally, two cattle showed centrilobular hepatic necrosis. In this study, S. obtusifolia collected from the same farm showed seasonal variation in toxicity. Poisoning by S. obtusifolia is an important cause of death of cattle in the Central Western region of Brazil. The toxicosis caused by this plant is similar to S. occidentalis poisoning; however, in S. obtusifolia poisoning, acute hepatic necrosis is sometimes present. PMID:25255730

  20. Paracetamol, alcohol and the liver

    PubMed Central

    Prescott, Laurie F

    2000-01-01

    It is claimed that chronic alcoholics are at increased risk of paracetamol (acetaminophen) hepatotoxicity not only following overdosage but also with its therapeutic use. Increased susceptibility is supposed to be due to induction of liver microsomal enzymes by ethanol with increased formation of the toxic metabolite of paracetamol. However, the clinical evidence in support of these claims is anecdotal and the same liver damage after overdosage occurs in patients who are not chronic alcoholics. Many alcoholic patients reported to have liver damage after taking paracetamol with ‘therapeutic intent’ had clearly taken substantial overdoses. No proper clinical studies have been carried out to investigate the alleged paracetamol–alcohol interaction and acute liver damage has never been produced by therapeutic doses of paracetamol given as a challenge to a chronic alcoholic. The paracetamol–alcohol interaction is complex; acute and chronic ethanol have opposite effects. In animals, chronic ethanol causes induction of hepatic microsomal enzymes and increases paracetamol hepatotoxicity as expected (ethanol primarily induces CYP2E1 and this isoform is important in the oxidative metabolism of paracetamol). However, in man, chronic alcohol ingestion causes only modest (about twofold) and short-lived induction of CYP2E1, and there is no corresponding increase (as claimed) in the toxic metabolic activation of paracetamol. The paracetamol–ethanol interaction is not specific for any one isoform of cytochrome P450, and it seems that isoenzymes other than CYP2E1 are primarily responsible for the oxidative metabolism of paracetamol in man. Acute ethanol inhibits the microsomal oxidation of paracetamol both in animals and man. This protects against liver damage in animals and there is evidence that it also does so in man. The protective effect disappears when ethanol is eliminated and the relative timing of ethanol and paracetamol intake is critical. In many of the reports where it is alleged that paracetamol hepatotoxicity was enhanced in chronic alcoholics, the reverse should have been the case because alcohol was actually taken at the same time as the paracetamol. Chronic alcoholics are likely to be most vulnerable to the toxic effects of paracetamol during the first few days of withdrawal but maximum therapeutic doses given at this time have no adverse effect on liver function tests. Although the possibility remains that chronic consumption of alcohol does increase the risk of paracetamol hepatotoxicity in man (perhaps by impairing glutathione synthesis), there is insufficient evidence to support the alleged major toxic interaction. It is astonishing that clinicians and others have unquestion-ingly accepted this supposed interaction in man for so long with such scant regard for scientific objectivity. PMID:10759684

  1. ‘Turning a blind eye’: denying people their right to treatment for acute alcohol, drug and mental health conditions – an act of discrimination

    Microsoft Academic Search

    Jacky Talmet; Charlotte de Crespigny; Lynette Cusack; Peter Athanasos

    2009-01-01

    Background: Australians seeking health care from any public hospital have the right to non-discriminatory safe medical assessment, treatment and nursing care. The literature clearly indicates that people presenting to public hospitals with acute alcohol- or drug-related conditions are at risk of dying by being denied medical and nursing treatment. This denial of treatment is on the basis that their presumed

  2. Differential Regulation of TGF-?/Smad Signaling in Hepatic Stellate Cells between Acute and Chronic Liver Injuries.

    PubMed

    Yoshida, Katsunori; Matsuzaki, Koichi

    2012-01-01

    Current evidence suggests that regulation of extracellular matrix (ECM) accumulation by fibrogenic transforming growth factor (TGF)-? and platelet-derived growth factor (PDGF) signals involves different mechanisms in acute and chronic liver injuries, even though hepatic stellate cells (HSC) are the principal effecter in both cases. As a result of chronic liver damage, HSC undergo progressive activation to become myofibroblasts (MFB)-like cells. Our current review will discuss the differential regulation of TGF-? signaling between HSC and MFB in vitro and in vivo. Smad proteins, which convey signals from TGF-? receptors to the nucleus, have intermediate linker regions between conserved Mad-homology (MH) 1 and MH2 domains. TGF-? type I receptor and Ras-associated kinases differentially phosphorylate Smad2 and Smad3 to create COOH-terminally (C), linker (L), or dually (L/C) phosphorylated (p) isoforms. After acute liver injury, TGF-? and PDGF synergistically promote collagen synthesis in the activated HSC via pSmad2L/C and pSmad3L/C pathways. To avoid unlimited ECM deposition, Smad7 induced by TGF-? negatively regulates the fibrogenic TGF-? signaling. In contrast, TGF-? and PDGF can transmit the fibrogenic pSmad2L/C and mitogenic pSmad3L signals in MFB throughout chronic liver injury, because Smad7 cannot be induced by the pSmad3L pathway. This lack of Smad7 induction might lead to constitutive fibrogenesis in MFB, which eventually develop into accelerated liver fibrosis. PMID:22457652

  3. RNA-Sequencing Analysis of 5' Capped RNAs Identifies Many New Differentially Expressed Genes in Acute Hepatitis C Virus Infection

    PubMed Central

    Papic, Neven; Maxwell, Christopher I.; Delker, Don A.; Liu, Shuanghu; Heale, Bret S. E.; Hagedorn, Curt H.

    2012-01-01

    We describe the first report of RNA sequencing of 5' capped (Pol II) RNAs isolated from acutely hepatitis C virus (HCV) infected Huh 7.5 cells that provides a general approach to identifying differentially expressed annotated and unannotated genes that participate in viral-host interactions. We identified 100, 684, and 1,844 significantly differentially expressed annotated genes in acutely infected proliferative Huh 7.5 cells at 6, 48, and 72 hours, respectively (fold change ? 1.5 and Bonferroni adjusted p-values < 0.05). Most of the differentially expressed genes (>80%) and biological pathways (such as adipocytokine, Notch, Hedgehog and NOD-like receptor signaling) were not identified by previous gene array studies. These genes are critical components of host immune, inflammatory and oncogenic pathways and provide new information regarding changes that may benefit the virus or mediate HCV induced pathology. RNAi knockdown studies of newly identified highly upregulated FUT1 and KLHDC7B genes provide evidence that their gene products regulate and facilitate HCV replication in hepatocytes. Our approach also identified novel Pol II unannotated transcripts that were upregulated. Results further identify new pathways that regulate HCV replication in hepatocytes and suggest that our approach will have general applications in studying viral-host interactions in model systems and clinical biospecimens. PMID:22590687

  4. Acute inflammatory demyelinating polyneuropathy associated with pegylated interferon ? 2a therapy for chronic hepatitis C virus infection

    PubMed Central

    Khiani, Vijay; Kelly, Thomas; Shibli, Adeel; Jensen, Donald; Mohanty, Smruti R

    2008-01-01

    The combination of pegylated interferon (Peg-IFN) and ribavirin is the standard of care for chronic hepatitis C virus (HCV) infection treatment. In general, common side effects related to this combination therapy are mild and are very well tolerated. However, peripheral neuropathy including demyelinating polyneuropathy related to Peg-IFN is extremely rare. We present the first case of an acute inflammatory demyelinating polyneuropathy (AIDP) associated with Peg-IFN-? 2a (Pegasys) after 16 wk of a combination therapy with Pegasys and ribavirin in a 65-year-old woman with chronic HCV infection. She developed tingling, numbness, and weakness of her upper and lower extremities and was hospitalized for acute neurological deficits. Her clinical course, neurological findings, an electromyogram (EMG), nerve conductions studies (NCS), muscle biopsy, and a sural nerve biopsy were all consistent with AIDP likely related to Pegasys use. The patient recovered completely with the use of intravenous immunoglobulin (IVIG) including physical therapy and neurological rehabilitation. It is very important that gastroenterologists and/or hepatologists recognize this rare neurological complication related to Peg-IFN treatment very early, since it requires a prompt discontinuation of therapy including an immediate referral to a neurologist for the confirmation of diagnosis, management, and the prevention of long-term neurological deficits. PMID:18186575

  5. Rhabdomyolysis due to Lamivudine administration in acute viral hepatitis B infection: a case report from Malaysia

    PubMed Central

    Baharin, Janudin; Sahari, Narisa Sulaiman; Lim, Sazlyna Mohd Sazlly

    2014-01-01

    Rhabdomyolysis is a serious but rare side effect of Lamivudine treatment. Therefore, appropriate biochemical monitoring should be undertaken when it is used in the treatment of hepatitis B. This paper presents a case of Lamivudine-associated rhabdomyolysis in a 31-year-old man with congenital heart disease and hepatitis B. Three days after starting Lamivudine, the patient developed myalgia. Significant muscle tenderness and swelling of the upper and lower limbs was discovered during a physical examination. Creatine kinase was markedly raised. Lamivudine-induced rhabdomyolysis was suspected and the drug was discontinued. Symptoms and creatine kinase activity improved within four days of Lamivudine cessation and hydration. Early identification of Lamivudine-induced rhabdomyolysis is key in preventing this potentially fatal drug reaction; withdrawal of Lamivudine may contribute to complete remission of rhabdomyolysis. PMID:25763159

  6. Effects of acute doxorubicin treatment on hepatic proteome lysine acetylation status and the apoptotic environment

    PubMed Central

    Dirks-Naylor, Amie J; Kouzi, Samir A; Bero, Joseph D; Tran, Ngan TK; Yang, Sendra; Mabolo, Raean

    2014-01-01

    AIM: To determine if doxorubicin (Dox) alters hepatic proteome acetylation status and if acetylation status was associated with an apoptotic environment. METHODS: Doxorubicin (20 mg/kg; Sigma, Saint Louis, MO; n = 8) or NaCl (0.9%; n = 7) was administered as an intraperitoneal injection to male F344 rats, 6-wk of age. Once animals were treated with Dox or saline, all animals were fasted until sacrifice 24 h later. RESULTS: Dox treatment decreased proteome lysine acetylation likely due to a decrease in histone acetyltransferase activity. Proteome deacetylation may likely not be associated with a proapoptotic environment. Dox did not increase caspase-9, -8, or -3 activation nor poly (adenosine diphosphate-ribose) polymerase-1 cleavage. Dox did stimulate caspase-12 activation, however, it likely did not play a role in apoptosis induction. CONCLUSION: Early effects of Dox involve hepatic proteome lysine deacetylation and caspase-12 activation under these experimental conditions. PMID:25225604

  7. Acute alcohol effects on impulsivity: Associations with drinking and driving behavior

    PubMed Central

    McCarthy, Denis M.; Niculete, Maria E.; Treloar, Hayley R.; Morris, David H.; Bartholow, Bruce D.

    2012-01-01

    Aims Although drink drivers exhibit higher levels of trait impulsivity, no studies have tested the hypothesis that drink drivers experience increased impulsivity while intoxicated. We tested this hypothesis for two impulsivity constructs: delay discounting and behavioral inhibition. Design A within-subjects study comparing performance of drink drivers and non-drink drivers on behavioral measures of impulsivity in alcohol and no-beverage sessions. Setting A laboratory setting at the University of Missouri. Participants Twenty-nine young adults who were at least moderate drinkers were recruited from the local community and the University of Missouri. Measurements Impulsivity was assessed using the Two Choice Impulsivity Paradigm (TCIP) and the Stop-Signal Task. Participants also completed self-report measures of binge drinking and trait impulsivity. Findings In the no-beverage session, TCIP impulsive choices did not differ between drinking and driving groups (p = .93). In the alcohol session, drink drivers made more TCIP impulsive choices on both the ascending (p < .01) and descending limb (p < .01) of the blood alcohol concentration curve than their peers who did not drink and drive. Drinking and driving groups did not differ on the Stop-Signal Task. Supplementary analyses indicated that effects for the TCIP were not explained by individual differences in trait impulsivity. Conclusions Individuals who report having three or more drinks before driving show greater impulsivity when under the influence of alcohol than those who do not report heavy drinking before driving. PMID:22690907

  8. Heart Rate Variability and Sympathetic Skin Response in Male Patients Suffering From Acute Alcohol Withdrawal Syndrome

    Microsoft Academic Search

    Karl-Jurgen Bar; Michael Karl Boettger; Rene Neubauer; Marei Groteluschen; Thomas Jochum; Vico Baier; Heinrich Sauer; Andreas Voss

    2006-01-01

    Background: Many symptoms of alcohol withdrawal (AW) such as tachycardia or elevated blood pressure might be explained by increased peripheral and central adrenergic activity. In contrast to many neurochemical studies of sympathetic activation during AW, only very few studies investigated autonomic balance using neurophysiological methods. Methods: We investigated heart rate variability (HRV) and sympathetic skin response (SSR) in male patients

  9. Acute hepatitis B despite a previous high titer of anti-HBs

    Microsoft Academic Search

    Resat OzarasCem ArSeniz Ongoren; Cem Ar; Seniz Ongoren; Bilgul Mete; Fehmi Tabak; Ali Mert; Recep Ozturk

    2010-01-01

    Introduction  Loss of HBsAg and development of surface and core antibodies represent clinical cure. However, recent evidence suggests that\\u000a hepatitis B virus (HBV) persists in a latent state even in those with mounted protective antibodies. After significant immunosuppression,\\u000a anti-HBs may decrease and HBsAg may reappear (reverse seroconversion). Reverse seroconversion of HBV has been observed in\\u000a association with hematopoietic stem cell transplantation,

  10. Differential regulation of TGF-? signal in hepatic stellate cells between acute and chronic rat liver injury

    Microsoft Academic Search

    Yoshiya Tahashi; Koichi Matsuzaki; Masataka Date; Katsunori Yoshida; Fukiko Furukawa; Yasushi Sugano; Masanori Matsushita; Yasuo Himeno; Yutaka Inagaki; Kyoichi Inoue

    2002-01-01

    During chronic liver injury, transforming growth factor ? (TGF-?) plays a prominent role in stimulating liver fibrogenesis by myofibroblast-like cells derived from hepatic stellate cells (HSCs). On the other hand, Smad 7 was recently shown to antagonize the TGF-?–induced activation of signal-transducing Smads (2 and 3). In this study, we investigated the regulatory mechanisms of the TGF-? signals in rat

  11. Protective Effects of Pretreatment with Oleanolic Acid in Rats in the Acute Phase of Hepatic Ischemia-Reperfusion Injury: Role of the PI3K/Akt Pathway

    PubMed Central

    Gui, Bo; Hua, Fuzhou; Chen, Jie; Xu, Zeping; Sun, Hongbin; Qian, Yanning

    2014-01-01

    Oleanolic acid (OA) has been used to treat liver disorders, but whether it can attenuate hepatic ischemia-reperfusion- (IR-) associated liver dysfunction remains unexplored. In the present study, 160 male Sprague-Dawley rats were equally divided into five groups: group SH received neither hepatic IR nor drugs; group IR received hepatic IR without drugs; group CM and group OA received 0.5% sodium carboxymethylcellulose and 100?mg/kg OA, intragastrically, once a day for seven days before the hepatic IR, respectively; on the basis of treatment in group OA, group OA+wortmannin further received 15??g/kg of PI3K inhibitor wortmannin, intraperitoneally, 30?min before the hepatic IR. Then each group was equally divided into four subgroups according to four time points (preoperation, 0?h, 3?h, and 6?h after reperfusion). Serum ALT activity, IL-1? concentration, and hepatic phosphorylation of PI3K, Akt, and GSK-3? protein expression were serially studied. We found that OA pretreatment improved histological status and decreased serum ALT and IL-1? levels. It also increased p-PI3K, p-Akt, and p-GSK-3? protein expression at all the four time points. Prophylactic wortmannin partially reversed OA's protective effects. The data indicate that OA pretreatment protects liver from IR injury during the acute phase partially through PI3K/Akt-mediated inactivation of GSK-3?. PMID:24829521

  12. New Point Mutations in Surface and Core Genes of Hepatitis B Virus Associated with Acute on Chronic Liver Failure Identified by Complete Genomic Sequencing

    PubMed Central

    Lou, Guohua; Zheng, Min; Cao, Qingyi; Chen, Zhi

    2015-01-01

    The objective of this study was to identify new viral biomarkers associated with acute on chronic liver failure (ACLF) by complete genomic sequencing of HBV. Hepatitis B virus mutations associated with ACLF were screened by Illumina high-throughput sequencing in twelve ACLF cases and twelve age-matched mild chronic hepatitis B patients, which were validated in 438 chronic hepatitis B patients (80 asymptomatic carriers, 152 mild chronic hepatitis B patients, 102 severe chronic hepatitis B patients and 104 ACLF patients) by direct sequencing. The results of Illumina sequencing showed that the mutations at 7 sites (T216C, G285A, A1846T, G1896A, C1913A/G, A2159G, and A2189C) of 12 ACLF patients were significantly higher than those of 12 controls. In the validation cohorts, a significantly higher ratio of genotype B to C was found in patients with ACLF than in patients with non-ACLF. Multivariate analysis showed that T216C, G1896A, C1913A/G and A2159G/C were independent risk factors for ACLF. C216 in any combination, A/G1913 in any combination, and G/C2159 in any combination had high specificity for ACLF. In summary, T216C and A2159G/C mutations were novel factors independently associated with ACLF. Combined mutations in hepatitis B cases could play important roles in ACLF development. PMID:25849554

  13. A major QTL for acute ethanol sensitivity in the alcohol tolerant and non-tolerant selected rat lines.

    PubMed

    Radcliffe, R A; Erwin, V G; Bludeau, P; Deng, X; Fay, T; Floyd, K L; Deitrich, R A

    2009-08-01

    The Alcohol Tolerant and Alcohol Non-Tolerant rats (AT, ANT) were selectively bred for ethanol-induced ataxia as measured on the inclined plane. Here we report on a quantitative trait locus (QTL) study in an F(2) intercross population derived from inbred AT and ANT (IAT, IANT) and a follow-up study of congenics that were bred to examine one of the mapped QTLs. Over 1200 F(2) offspring were tested for inclined plane sensitivity, acute tolerance on the inclined plane, duration of the loss of righting reflex (LORR) and blood ethanol at regain of the righting reflex (BECRR). F(2) rats that were in the upper and lower 20% for inclined plane sensitivity were genotyped with 78 SSLP markers. Significant QTLs for inclined plane sensitivity were mapped on chromosomes 8 and 20; suggestive QTLs were mapped on chromosomes 1, 2 and 3. Highly significant QTLs for LORR duration (LOD = 12.4) and BECRR (LOD = 5.7) were mapped to the same locus on chromosome 1. Breeding and testing of reciprocal congenic lines confirmed the chromosome 1 LORR/BECRR QTL. A series of recombinant congenic sub-lines were bred to fine-map this QTL. Current results have narrowed the QTL to an interval of between 5 and 20 Mb. We expect to be able to narrow the interval to less than 5 Mb with additional genotyping and continued breeding of recombinant sub-congenic lines. PMID:19500156

  14. Improvement of Carbon Tetrachloride-Induced Acute Hepatic Failure by Transplantation of Induced Pluripotent Stem Cells without Reprogramming Factor c-Myc

    PubMed Central

    Chang, Hua-Ming; Liao, Yi-Wen; Chiang, Chih-Hung; Chen, Yi-Jen; Lai, Ying-Hsiu; Chang, Yuh-Lih; Chen, Hen-Li; Jeng, Shaw-Yeu; Hsieh, Jung-Hung; Peng, Chi-Hsien; Li, Hsin-Yang; Chien, Yueh; Chen, Szu-Yu; Chen, Liang-Kung; Huo, Teh-Ia

    2012-01-01

    The only curative treatment for hepatic failure is liver transplantation. Unfortunately, this treatment has several major limitations, as for example donor organ shortage. A previous report demonstrated that transplantation of induced pluripotent stem cells without reprogramming factor c-Myc (3-genes iPSCs) attenuates thioacetamide-induced hepatic failure with minimal incidence of tumorigenicity. In this study, we investigated whether 3-genes iPSC transplantation is capable of rescuing carbon tetrachloride (CCl4)-induced fulminant hepatic failure and hepatic encephalopathy in mice. Firstly, we demonstrated that 3-genes iPSCs possess the capacity to differentiate into hepatocyte-like cells (iPSC-Heps) that exhibit biological functions and express various hepatic specific markers. 3-genes iPSCs also exhibited several antioxidant enzymes that prevented CCl4-induced reactive oxygen species production and cell death. Intraperitoneal transplantation of either 3-genes iPSCs or 3-genes iPSC-Heps significantly reduced hepatic necrotic areas, improved hepatic functions, and survival rate in CCl4-treated mice. CCl4-induced hepatic encephalopathy was also improved by 3-genes iPSC transplantation. Hoechst staining confirmed the successful engraftment of both 3-genes iPSCs and 3-genes iPSC-Heps, indicating the homing properties of these cells. The most pronounced hepatoprotective effect of iPSCs appeared to originate from the highest antioxidant activity of 3-gene iPSCs among all transplanted cells. In summary, our findings demonstrated that 3-genes iPSCs serve as an available cell source for the treatment of an experimental model of acute liver diseases. PMID:22489170

  15. CAGE, RAPS4, RAPS4-QF and AUDIT Screening Tests for Men and Women Admitted for Acute Alcohol Intoxication to an Emergency Department: Are Standard Thresholds Appropriate?

    PubMed Central

    Geneste, J.; Pereira, B.; Arnaud, B.; Christol, N.; Liotier, J.; Blanc, O.; Teissedre, F.; Hope, S.; Schwan, R.; Llorca, P.M.; Schmidt, J.; Cherpitel, C.J.; Malet, L.; Brousse, G.

    2012-01-01

    Aims: A number of screening instruments are routinely used in Emergency Department (ED) situations to identify alcohol-use disorders (AUD). We wished to study the psychometric features, particularly concerning optimal thresholds scores (TSs), of four assessment scales frequently used to screen for abuse and/or dependence, the cut-down annoyed guilty eye-opener (CAGE), Rapid Alcohol Problem Screen 4 (RAPS4), RAPS4-quantity-frequency and AUD Identification Test (AUDIT) questionnaires, particularly in the sub-group of people admitted for acute alcohol intoxication (AAI). Methods: All included patients [AAI admitted to ED (blood alcohol level ?0.8 g/l)] were assessed by the four scales, and with a gold standard (alcohol dependence?abuse section of the Mini International Neuropsychiatric Interview), to determine AUD status. To investigate the TSs of the scales, we used Youden's index, efficiency, receiver operating characteristic (ROC) curve techniques and quality ROC curve technique for optimized TS (indices of quality). Results: A total of 164 persons (122 males, 42 females) were included in the study. Nineteen (11.60%) were identified as alcohol abusers alone and 128 (78.1%) as alcohol dependents (DSM-IV). Results suggest a statistically significant difference between men and women (P < 0.05) in performance of the screening tests RAPS4 (?1) and CAGE (?2) for detecting abuse. Also, in this population, we show an increase in TSs of RAPS4 (?2) and CAGE (?3) for detecting dependence compared with those typically accepted in non-intoxicated individuals. The AUDIT test demonstrates good performance for detecting alcohol abuse and/or alcohol-dependent patients (?7 for women and ?12 for men) and for distinguishing alcohol dependence (?11 for women and ?14 for men) from other conditions. Conclusion: Our study underscores for the first time the need to adapt, taking into account gender, the thresholds of tests typically used for detection of abuse and dependence in this population. PMID:22414922

  16. Event-Related Potential responses to the acute and chronic effects of alcohol in adolescent and adult Wistar rats

    PubMed Central

    Ehlers, Cindy L.; Desikan, Anita; Wills, Derek N.

    2014-01-01

    Background The present study explored the hypothesis that adolescent ethanol exposure may cause long lasting changes in ethanol sensitivity by exploring the age-related effects of acute alcohol on intoxication and on event-related potential (ERP) responses to acoustic stimuli in ethanol naïve adolescent and adult male Wistar rats and in adult rats that were exposed to chronic ethanol/control conditions during adolescence. Methods Ethanol naïve adolescent (postnatal day 32 (PD32)) and adult male rats (PD99) were included in the first study. In a second study, rats were exposed to 5 weeks of ethanol vapor (Blood ethanol concentrations @ 175 mg%) or air from PD24 to PD59 and allowed to mature until PD90. In both studies rats were implanted with cortical recording electrodes, and the effects of acute ethanol (0.0, 1.5, and 3.0 g/kg) on behavioral and ERP responses were assessed. Results Adolescents were found to have higher amplitude and longer latency P3a and P3b components at baseline as compared to adult rats, and ethanol was found to produce a robust dose-dependent increase in the latency of the P3a and P3b components of the auditory ERP recorded in cortical sites in both adolescents and adults. However, ethanol produced significantly larger delays in P3a and P3b latencies in adults as compared to adolescents. Acute ethanol administration was also found to produce a robust dose dependent increase in the latency of the P3a and P3b components in adult animals exposed to ethanol vapor as adolescents and air exposed controls; however, larger acute ethanol-induced increases in P3a and P3b latencies were seen in controls as compared to adolescent vapor exposed rats. Conclusions Adolescent rats have a less intense P3 latency response to acute ethanol administration when compared to adult rats. Exposure to chronic ethanol during adolescence can cause “retention” of the adolescent phenotype of reduced P3 latency sensitivity to ethanol. PMID:24483322

  17. SURVIVAL IN INFECTION-RELATED ACUTE-ON-CHRONIC LIVER FAILURE IS DEFINED BY EXTRA-HEPATIC ORGAN FAILURES

    PubMed Central

    Bajaj, Jasmohan S; O’Leary, Jacqueline G; Reddy, K Rajender; Wong, Florence; Biggins, Scott W.; Patton, Heather; Fallon, Michael B; Garcia-Tsao, Guadalupe; Maliakkal, Benedict; Malik, Raza; Subramanian, Ram M; Thacker, Leroy R; Kamath, Patrick S

    2014-01-01

    Background Infections worsen survival in cirrhosis; however, simple predictors of survival in infection-related acute-on-chronic liver failure (I-ACLF) derived from multi-center studies are required in order to improve prognostication and resource allocation. Methods Using the NACSELD database, data from 18 centers were collected for survival analysis of prospectively enrolled cirrhotic patients hospitalized with an infection. We defined organ failures as (i) shock, (ii) grade III/IV hepatic encephalopathy(HE), (iii) need for dialysis (iv) mechanical ventilation. Determinants of survival with these organ failures were analyzed. Results 507 patients were included (55 yrs, 52% HCV, 15.8% nosocomial infection, 96% Child score?7) and 30-day evaluations were available in 453 patients. Urinary tract infection (UTI) (28.5%), and spontaneous bacterial peritonitis (SBP) (22.5%) were most prevalent. During hospitalization, 55.7% developed HE, 17.6% shock, 15.1% required renal replacement, and 15.8% needed ventilation; 23% died within 30-days and 21.6% developed second infections. Admitted patients developed none (38.4%), one (37.3%), two (10.4%), three (10%) or four (4%) organ failures. 30-day survival worsened with higher number of extra-hepatic organ failures, none (92%), one (72.6%), two (51.3%), three (36%) and all four (23%). I-ACLF was defined as ?2 organ failures given the significant change in survival probability associated at this cutoff. Baseline independent predictors for development of ACLF were nosocomial infections, MELD score, low mean arterial pressure (MAP), and non-SBP infections. Independent predictors of poor 30-day survival were I-ACLF, second infections, and admission values of high MELD, low MAP, high white blood count and low albumin. In conclusion, using multi-center study data in hospitalized decompensated infected cirrhotic patients, I-ACLF defined by the presence of two or more organ failures using simple definitions is predictive of poor survival. PMID:24677131

  18. High Dose Lycopene Supplementation Increases Hepatic CYP2E1 Protein and Inflammation in Alcohol-Fed Rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent in vitro evidence suggests that the antioxidant lycopene can prevent alcohol induced oxidative stress and inflammation. However, in vivo knowledge of possible interactions between escalating doses of lycopene and chronic alcohol ingestion are lacking. In the present study, we investigated p...

  19. Acute hemorrhage causes hepatic insulin sensitizing substance (HISS)-dependent insulin resistance.

    PubMed

    Seredycz, Larissa I; Ming, Zhi; Lautt, W Wayne

    2006-11-01

    Hepatic insulin sensitizing substance (HISS) has been shown to account for 55% of the action of insulin in the fed state. HISS blockade leads to HISS-dependent insulin resistance (HDIR). The objective of this study was to test the hypothesis that insulin resistance produced by hemorrhage was HDIR. Insulin sensitivity was measured using the rapid insulin sensitivity test (RIST), which can identify HISS-dependent and independent components. Hemorrhage was performed in anesthetized rats by removing blood to reduce mean arterial pressure to 50 mmHg. Subsequent to blood removal, a RIST was performed. The results show that hemorrhage caused complete HDIR as subsequent administration of atropine failed to further reduce insulin sensitivity. However, the post-hemorrhage RIST was reduced by 34% and not the anticipated 55%. The lesser reduction of the RIST index by hemorrhage was related to reduced apparent volume of distribution and clearance of insulin, since occlusion of the superior mesenteric artery, which caused a similar decrease in portal venous flow as did hemorrhage, resulted in a similar degree of reduction of insulin clearance. The response to administered insulin was confounded by the impact of reduced hepatic blood flow on insulin metabolism that resulted in an increase in the HISS independent (direct) action of injected insulin against a background of complete HDIR. HDIR represents a useful hormonal response to assure a hyperglycemic response to hemorrhage. PMID:17218979

  20. A novel hypothesis for an alkaline phosphatase 'rescue' mechanism in the hepatic acute phase immune response.

    PubMed

    Pike, Adrianne F; Kramer, Nynke I; Blaauboer, Bas J; Seinen, Willem; Brands, Ruud

    2013-12-01

    The liver isoform of the enzyme alkaline phosphatase (AP) has been used classically as a serum biomarker for hepatic disease states such as hepatitis, steatosis, cirrhosis, drug-induced liver injury, and hepatocellular carcinoma. Recent studies have demonstrated a more general anti-inflammatory role for AP, as it is capable of dephosphorylating potentially deleterious molecules such as nucleotide phosphates, the pathogenic endotoxin lipopolysaccharide (LPS), and the contact clotting pathway activator polyphosphate (polyP), thereby reducing inflammation and coagulopathy systemically. Yet the mechanism underlying the observed increase in liver AP levels in circulation during inflammatory insults is largely unknown. This paper hypothesizes an immunological role for AP in the liver and the potential of this system for damping generalized inflammation along with a wide range of ancillary pathologies. Based on the provided framework, a mechanism is proposed in which AP undergoes transcytosis in hepatocytes from the canalicular membrane to the sinusoidal membrane during inflammation and the enzyme's expression is upregulated as a result. Through a tightly controlled, nucleotide-stimulated negative feedback process, AP is transported in this model as an immune complex with immunoglobulin G by the asialoglycoprotein receptor through the cell and secreted into the serum, likely using the receptor's State 1 pathway. The subsequent dephosphorylation of inflammatory stimuli by AP and uptake of the circulating immune complex by endothelial cells and macrophages may lead to decreased inflammation and coagulopathy while providing an early upstream signal for the induction of a number of anti-inflammatory gene products, including AP itself. PMID:23899605

  1. [Factors inducing clinical symptoms of acute hepatic porphyria 1986-1990].

    PubMed

    Tarczy?ska-Nosal, S; Ekiert, M; Kostrzewska, E

    1991-01-01

    The most frequent cause of porphyria attacks in this time period were drugs used in symptomatic treatment (in 69 out of 195 cases). In 42 women attacks were induced by sex hormone disturbances, in 21 cases by contact with paints and lacquer in 7 by alcohol and in 3 by calorie deficiencies. The main cause of porphyria attacks in carriers of this metabolic error is lack of porphyria considering in the differential diagnosis of abdominal pains, polyneuropathy and vague mental disorders, which leads to erroneous treatment worsening the course and prognosis of the disease. PMID:1823950

  2. Zingiber officinale Roscoe prevents acetaminophen-induced acute hepatotoxicity by enhancing hepatic antioxidant status

    Microsoft Academic Search

    T. A. Ajith; U. Hema; M. S. Aswathy

    2007-01-01

    A large number of xenobiotics are reported to be potentially hepatotoxic. Free radicals generated from the xenobiotic metabolism can induce lesions of the liver and react with the basic cellular constituents – proteins, lipids, RNA and DNA. Hepatoprotective activity of aqueous ethanol extract of Zingiber officinale was evaluated against single dose of acetaminophen-induced (3g\\/kg, p.o.) acute hepatotoxicity in rat. Aqueous

  3. The sequence and phylogenetic analysis of a novel hepatitis E virus isolated from a patient with acute hepatitis reported in the United States

    Microsoft Academic Search

    George G. Schlauder; George J. Dawson; James C. Erker; Paul Y. Kwo; Mark F. Knigge; David L. Smalley; Jon E. Rosenblatt; Suresh M. Desai; Isa K. Mushahwar

    1998-01-01

    A variant of hepatitis E virus (HEV), designated HEV US-1, was identified in a hepatitis patient in the United States (US); the patient had no history of travel to areas where HEV is endemic. Nucleotide sequences were obtained from the 5« end of open reading frame (ORF) 1 (1418 nt), the 3« end of ORF1 (1359 nt), the entire ORF2

  4. Protective effect of mesenchymal stem cell-conditioned medium on hepatic cell apoptosis after acute liver injury

    PubMed Central

    Xagorari, Angeliki; Siotou, Eleni; Yiangou, Minas; Tsolaki, Eleftheria; Bougiouklis, Dimitris; Sakkas, Leonidas; Fassas, Athanassios; Anagnostopoulos, Achilles

    2013-01-01

    The aim of this study was to investigate the role of Mesenchymal Stem Cell (MSC) conditioned medium (CMMSC) on apoptosis of cultured mouse primary hepatocytes after in vivo carbon tetrachloride (CCl4)-induced acute liver injury. The acute liver injury was induced by injecting CCl4 intraperitoneally in C57/BL6 mice. Hepatocytes were isolated by liver perfusion, cultured in a defined medium to maintain their differentiation and characterized by reverse transcriptase polymerase chain reaction (RT-PCR) using the hepatic cell specific genes albumin, hepatocyte nuclear factor 4 (HNF4) and cytokeratin 18 (CK18). CMMSC was generated from cultured bone marrow-derived MSCs (BM-MSCs). BM-MSCs were positive for CD73, CD90, CD44 by flow cytometry and able to differentiate into chondrocytes, adipocytes and osteocytes. Apoptosis was evaluated by both annexin V. CMMSC were examined by flow cytometry to detect MSC-derived annexin V- and CD54/CD44-positive microparticles (MPs). In the CCl4-CMMSC treated hepatocytes, interleukin-6 (IL-6) was increased on the first day of culture compared to control and CCl4 and was followed by upregulation of fibroblast-like-protein (FGL1) expression after 48 hrs. This was associated with a significant decrease of annexin V positive CCl4-CMMSC treated hepatocytes at day 3 post plating. Recombinant IL-6 was induced FGL1 expression in hepatocytes derived from CCl4-treated mice suggesting that CMMSC, which is enriched also in microparticles, attenuates CCl4-induced early apoptosis in hepatocytes through activation of FGL1. PMID:23638214

  5. Protective effect of mesenchymal stem cell-conditioned medium on hepatic cell apoptosis after acute liver injury.

    PubMed

    Xagorari, Angeliki; Siotou, Eleni; Yiangou, Minas; Tsolaki, Eleftheria; Bougiouklis, Dimitris; Sakkas, Leonidas; Fassas, Athanassios; Anagnostopoulos, Achilles

    2013-01-01

    The aim of this study was to investigate the role of Mesenchymal Stem Cell (MSC) conditioned medium (CM(MSC)) on apoptosis of cultured mouse primary hepatocytes after in vivo carbon tetrachloride (CCl4)-induced acute liver injury. The acute liver injury was induced by injecting CCl4 intraperitoneally in C57/BL6 mice. Hepatocytes were isolated by liver perfusion, cultured in a defined medium to maintain their differentiation and characterized by reverse transcriptase polymerase chain reaction (RT-PCR) using the hepatic cell specific genes albumin, hepatocyte nuclear factor 4 (HNF4) and cytokeratin 18 (CK18). CM(MSC) was generated from cultured bone marrow-derived MSCs (BM-MSCs). BM-MSCs were positive for CD73, CD90, CD44 by flow cytometry and able to differentiate into chondrocytes, adipocytes and osteocytes. Apoptosis was evaluated by both annexin V. CM(MSC) were examined by flow cytometry to detect MSC-derived annexin V- and CD54/CD44-positive microparticles (MPs). In the CCl4-CM(MSC) treated hepatocytes, interleukin-6 (IL-6) was increased on the first day of culture compared to control and CCl4 and was followed by upregulation of fibroblast-like-protein (FGL1) expression after 48 hrs. This was associated with a significant decrease of annexin V positive CCl4-CM(MSC) treated hepatocytes at day 3 post plating. Recombinant IL-6 was induced FGL1 expression in hepatocytes derived from CCl4-treated mice suggesting that CM(MSC), which is enriched also in microparticles, attenuates CCl4-induced early apoptosis in hepatocytes through activation of FGL1. PMID:23638214

  6. Alcohol induced diabetic ketoacidosis exacerbated by an acute respiratory infection with Klebsiella pneumoniae.

    PubMed

    Distel, Caleb; Jacobson, Stephanie; Tille, Patricia M

    2013-01-01

    Ketoacidosis is a metabolic condition that occurs as a result of an insufficient amount of insulin. The lack of insulin results in an increased release of glucose from the liver and an excess of ketone bodies as a result of the breakdown of adipose tissue. This occurs when carbohydrates are unable to be properly processed for needed energy requirements during cellular metabolism. Ketoacidosis is commonly linked to diabetes mellitus. Diabetes mellitus is a condition where the body is unable to produce the proper amount of insulin or is unable to effectively respond to insulin stimulation. Excessive alcohol use can damage the pancreas, reducing insulin secretion. Other conditions such as pneumonia or urinary tract infections can trigger the release of counter-regulatory hormones that may contribute to the decrease in insulin's activity and secretion. Symptoms of diabetic ketoacidosis often include nausea and vomiting, increased thirst and urine production, hyperglycemia, abdominal pain, shortness of breath, confusion, headache, general weakness, fatigue and increased heart rate. If left untreated, diabetic ketoacidosis can lead to more serious complications including circulatory collapse, decreased blood potassium levels, infection and cerebral edema. The following case study presents a complex condition of ketoacidosis associated with a bacterial infection compounded by the patient's history of alcohol abuse. PMID:23772471

  7. Raised hepatic free fatty acids in a patient with acute fatty liver after gastric surgery for morbid obesity

    Microsoft Academic Search

    S R Cairns; A E Kark; T J Peters

    1986-01-01

    A patient died after gastric surgery for morbid obesity. Necropsy showed severe fatty liver, and biochemical analysis of hepatic lipids showed unusually high free fatty acid concentrations, which may have contributed to the hepatic failure.

  8. Acute Interstitial Nephritis Proteinuria and Herpes Simplex Virus Hepatitis in Pregnancy Mimic HELLP Syndrome (Hemolysis, Elevated Liver Enzymes, Low Platelets)

    PubMed Central

    White, Wendy M.; Tran, Diana; Garovic, Vesna D.; Brost, Brian

    2011-01-01

    Elevated transaminases, hemolysis, and thrombocytopenia in pregnancy are most often caused by a preeclampsia variant—HELLP syndrome (hemolysis, elevated liver enzymes, low platelets). In atypical cases, it is important to consider other causes, such as herpes simplex virus (HSV) hepatitis. Acute interstitial nephritis (AIN)-induced proteinuria can make distinguishing HELLP from its mimics more difficult. A 43-year-old G4P3 gestational carrier at 28 weeks had abnormal laboratory findings consistent with HELLP, including proteinuria. However, she was normotensive and febrile, prompting an investigation into other possible causes of her signs and symptoms. She ultimately was diagnosed with disseminated HSV infection, started on definitive therapy, and allowed to continue her pregnancy to term. The proteinuria was attributed to AIN. AIN can cause proteinuria in the critically ill pregnant patient. When mimics of HELLP syndrome, such as disseminated HSV infection, are the cause of critical illness, the presence of AIN-induced proteinuria may falsely implicate a hypertensive disorder of pregnancy, resulting in iatrogenic premature delivery of the fetus and failure to initiate definitive potential lifesaving treatment. PMID:23705099

  9. Cx3cr1 deficiency in mice attenuates hepatic granuloma formation during acute schistosomiasis by enhancing the M2-type polarization of macrophages.

    PubMed

    Ran, Lin; Yu, Qilin; Zhang, Shu; Xiong, Fei; Cheng, Jia; Yang, Ping; Xu, Jun-Fa; Nie, Hao; Zhong, Qin; Yang, Xueli; Yang, Fei; Gong, Quan; Kuczma, Michal; Kraj, Piotr; Gu, Weikuan; Ren, Bo-Xu; Wang, Cong-Yi

    2015-07-01

    Acute schistosomiasis is characterized by pro-inflammatory responses against tissue- or organ-trapped parasite eggs along with granuloma formation. Here, we describe studies in Cx3cr1(-/-) mice and demonstrate the role of Cx3cr1 in the pathoetiology of granuloma formation during acute schistosomiasis. Mice deficient in Cx3cr1 were protected from granuloma formation and hepatic injury induced by Schistosoma japonicum eggs, as manifested by reduced body weight loss and attenuated hepatomegaly along with preserved liver function. Notably, S. japonicum infection induced high levels of hepatic Cx3cr1 expression, which was predominantly expressed by infiltrating macrophages. Loss of Cx3cr1 rendered macrophages preferentially towards M2 polarization, which then led to a characteristic switch of the host immune defense from a conventional Th1 to a typical Th2 response during acute schistosomiasis. This immune switch caused by Cx3cr1 deficiency was probably associated with enhanced STAT6/PPAR-? signaling and increased expression of indoleamine 2,3-dioxygenase (IDO), an enzyme that promotes M2 polarization of macrophages. Taken together, our data provide evidence suggesting that CX3CR1 could be a viable therapeutic target for treatment of acute schistosomiasis. PMID:26035381

  10. Cx3cr1 deficiency in mice attenuates hepatic granuloma formation during acute schistosomiasis by enhancing the M2-type polarization of macrophages

    PubMed Central

    Ran, Lin; Yu, Qilin; Zhang, Shu; Xiong, Fei; Cheng, Jia; Yang, Ping; Xu, Jun-Fa; Nie, Hao; Zhong, Qin; Yang, Xueli; Yang, Fei; Gong, Quan; Kuczma, Michal; Kraj, Piotr; Gu, Weikuan; Ren, Bo-Xu; Wang, Cong-Yi

    2015-01-01

    ABSTRACT Acute schistosomiasis is characterized by pro-inflammatory responses against tissue- or organ-trapped parasite eggs along with granuloma formation. Here, we describe studies in Cx3cr1?/? mice and demonstrate the role of Cx3cr1 in the pathoetiology of granuloma formation during acute schistosomiasis. Mice deficient in Cx3cr1 were protected from granuloma formation and hepatic injury induced by Schistosoma japonicum eggs, as manifested by reduced body weight loss and attenuated hepatomegaly along with preserved liver function. Notably, S. japonicum infection induced high levels of hepatic Cx3cr1 expression, which was predominantly expressed by infiltrating macrophages. Loss of Cx3cr1 rendered macrophages preferentially towards M2 polarization, which then led to a characteristic switch of the host immune defense from a conventional Th1 to a typical Th2 response during acute schistosomiasis. This immune switch caused by Cx3cr1 deficiency was probably associated with enhanced STAT6/PPAR-? signaling and increased expression of indoleamine 2,3-dioxygenase (IDO), an enzyme that promotes M2 polarization of macrophages. Taken together, our data provide evidence suggesting that CX3CR1 could be a viable therapeutic target for treatment of acute schistosomiasis. PMID:26035381

  11. [Signal averaging electrocardiography in chronic alcoholism].

    PubMed

    Pochmalicki, G; Genest, M; Jibril, A; Abdmoulah, M; Chatila, M; Zemir, H; Cayla, J M

    1998-03-01

    Cardiovascular death is the main cause of mortality in chronic alcoholics, perhaps due to a pro-arrhythmogenic effect of alcohol associated with infraclinical myocardial lesions. The authors investigated prospectively 41 patients (average age: 49.7 years) who were chronic alcoholics but had no acute alcoholic episodes for cardiac disease (ECG, signal averaging for late ventricular potentials, echocardiography and Holter ECG monitoring) and hepatic disease (liver biopsy). The history of alcoholism was 14 +/- 9 years, the quantity of alcohol ingested before they stopped drinking being 89 +/- 31 grammes/day. Thirty per cent of patients displayed 2 or 3 criteria of late ventricular potentials (LP). The authors demonstrated a correlation between the daily quantity of alcohol consumed before stopping drinking and the duration of the filtered QRS complex (p = 0.02). Moreover, the frequency of fatty infiltration found on liver biopsy, greater in alcoholics with LP (35% versus 19%, p = 0.025) correlated with the amplitude of the last 40 ms of the average QRS (p = 0.0485), with the duration of potentials of less than 40 microvolts (p = 0.05) and, above all, with the number of criteria of LP (p = 0.02). Finally, the presence of LP was also related to the following biological abnormalities: GGT (p = 0.027), ASAT (p = 0.046), ALAT (p = 0.039). The ECG abnormalities may reflect early infra-clinical myocardial lesions secondary to cellular metabolic abnormalities perhaps analogous to the fatty hepatic changes. However, the prognostic value of these signal-averaging ECG abnormalities remains unknown. PMID:9749235

  12. Indirect Effects of Acute Alcohol Intoxication on Sexual Risk-taking: The Roles of Subjective and Physiological Sexual Arousal

    Microsoft Academic Search

    William H. George; Kelly Cue Davis; Jeanette Norris; Julia R. Heiman; Susan A. Stoner; Rebecca L. Schacht; Christian S. Hendershot; Kelly F. Kajumulo

    2009-01-01

    Three experiments supported the idea that alcohol fosters sexual risk-taking in men and women, in part, through its effects\\u000a on sexual arousal. In Experiment 1, increasing alcohol dosage (target blood alcohol levels of .00, .04, .08%) heightened men’s\\u000a and women’s risk-taking intentions. Alcohol’s effect was indirect via increased subjective sexual arousal; also, men exhibited\\u000a greater risk-taking than women. In Experiment

  13. Alcoholic Lung Injury: Metabolic, Biochemical and Immunological Aspects

    PubMed Central

    Kaphalia, Lata; Calhoun, William J.

    2013-01-01

    Chronic alcohol abuse is a systemic disorder and a risk factor for acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD). A significant amount of ingested alcohol reaches airway passages in the lungs and can be metabolized via oxidative and non-oxidative pathways. About 90% of the ingested alcohol is metabolized via hepatic alcohol dehydrogenase (ADH)-catalyzed oxidative pathway. Alcohol can also be metabolized by cytochrome P450 2E1 (CYP2E1), particularly during chronic alcohol abuse. Both the oxidative pathways, however, are associated with oxidative stress due to the formation of acetaldehyde and/or reactive oxygen species (ROS). Alcohol ingestion is also known to cause endoplasmic reticulum (ER) stress, which can be mediated by oxidative and/or non-oxidative metabolites of ethanol. An acute as well as chronic alcohol ingestions impair protective antioxidants, oxidize reduced glutathione (GSH, cellular antioxidant against ROS and oxidative stress), and suppress innate and adaptive immunity in the lungs. Oxidative stress and suppressed immunity in the lungs of chronic alcohol abusers collectively are considered to be major risk factors for infection and development of pneumonia, and such diseases as ARDS and COPD. Prior human and experimental studies attempted to identify common mechanisms by which alcohol abuse directly causes toxicity to alveolar epithelium and respiratory tract, particularly lungs. In this review, the metabolic basis of lung injury, oxidative and ER stress and immunosuppression in experimental models and alcoholic patients, as well as potential immunomodulatory therapeutic strategies for improving host defenses against alcohol-induced pulmonary infections are discussed. PMID:23892124

  14. MR Imaging Findings in Alcoholic and Nonalcoholic Acute Wernicke's Encephalopathy: A Review

    PubMed Central

    Manzo, Gaetana; De Gennaro, Angela; Cozzolino, Attilio; Serino, Antonietta; Fenza, Giacomo; Manto, Andrea

    2014-01-01

    Wernicke's encephalopathy (WE) is a severe neurological syndrome caused by thiamine (vitamin B1) deficiency and clinically characterized by the sudden onset of mental status changes, ocular abnormalities, and ataxia. Apart from chronic alcoholism, the most common cause of WE, a lot of other conditions causing malnutrition and decreasing thiamine absorption such as gastrointestinal surgical procedures and hyperemesis gravidarum must be considered as predisposing factors. Due to its low prevalence and clinical heterogeneity, WE is often misdiagnosed, leading to persistent dysfunctions and, in some cases, to death. Nowadays, MR imaging of the brain, showing T2 and FLAIR hyperintensities in typical (thalami, mammillary bodies, tectal plate, and periaqueductal area) and atypical areas (cerebellum, cranial nerve nuclei, and cerebral cortex), is surely the most important and effective tool in the diagnostic assessment of WE. The aim of this paper is to propose a state of the art of the role of MR imaging in the early diagnosis of this complex disease. PMID:25050351

  15. Rapid Recovery from Acute Liver Failure Secondary to Pancreatoduodenectomy-Related Non-Alcoholic Steatohepatitis

    PubMed Central

    Nirei, Kazushige; Ogihara, Norikazu; Kawamura, Wataru; Kang, Woodea; Moriyama, Mitsuhiko

    2013-01-01

    This report describes a case of liver failure secondary to pancreatoduodenectomy and rapid recovery following treatment. A 68-year-old woman with cancer on the ampulla of Vater underwent surgery for pancreatoduodenectomy. The patient developed liver failure 3 months postsurgically. She was hospitalized after presenting with jaundice, hypoalbuminemia and decreased serum zinc. Computed tomography (CT) of the abdomen showed a reduction in CT attenuation values postoperatively. We suspected fatty liver due to impaired absorption caused by pancreatoduodenectomy. We initiated treatment with branched-chain amino acids and a zinc formulation orally. Trace elements were administered intravenously. Two months after treatment, there was a noticeable improvement in CT findings. The patient's jaundice and hypoalbuminemia prompted a liver biopsy, which led to a diagnosis of non-alcoholic steatohepatitis. PMID:23467319

  16. Acetaldehyde accumulation in rat mammary tissue after an acute treatment with alcohol.

    PubMed

    Castro, G D; Delgado de Layño, A M A; Fanelli, S L; Maciel, M E; Díaz Gómez, M I; Castro, J A

    2008-04-01

    Previous studies reported the presence in rat mammary tissue of a cytosolic xanthine oxidoreductase pathway for the metabolism of alcohol to acetaldehyde and hydroxyl radicals and to the microsomal biotransformation of ethanol to acetaldehyde. It was also reported that after chronic ethanol drinking stressful oxidative conditions can be observed. The present work reports that even after single doses of ethanol, given at three different levels (6.3 g kg(-1); 3.8 g kg(-1) or 0.6 g kg(-1) p.o.), acetaldehyde accumulates for prolonged periods of time in the mammary tissue to reach concentrations higher than in blood (e.g. 5.1+/-1.2 nmol g(-1) versus 0.2+/-0.1 nmol ml(-1), for 6.3 g kg(-1) dose, 6 h after intoxication). The presence in rat mammary tissue of low activities of additional enzymes able to generate acetaldehyde was established (alcohol dehydrogenase: 0.97+/-0.84 mU mg(-1) protein; CYP2E1: 1.30+/-0.12 x 10(-2) pmol 4-nitrocatechol min(-1) mg(-1) protein) and a low activity of aldehyde dehydrogenase was observed in the cytosolic, mitochondrial and microsomal fractions (0.02+/-0.04; 0.35+/-0.09 and 0.72+/-0.19 mU mg(-1) protein, respectively). After a single high dose of ethanol, an increased susceptibility to oxidative stress was observed, as evidenced by changes in the shape of t-butylhydroperoxide induced emission of chemiluminescence in mammary tissue (6.3 g kg(-1) dose; at 3 and 6 h). In summary, the results show that even after single doses of ethanol, acetaldehyde, either formed in situ or arriving via blood, tends to accumulate in mammary tissue and that this condition might decrease cell defenses against injury. PMID:17590863

  17. Alteration of factors associated with hepatic gluconeogenesis in response to acute lipopolysaccharide in dairy goat.

    PubMed

    Wang, L F; Yang, G Q; Yang, S; Yang, G Y; Li, M; Zhu, H S; Wang, Y Y; Han, L Q; Liu, R Y; Jia, S D; Song, F

    2015-06-01

    Lipopolysaccharide (LPS) is a common pathogenic agent that causes many diseases and metabolic disorders. Hypoglycemia is often observed when animals are infected with LPS. To explore the influence of LPS on blood glucose and hepatic gluconeogenesis in goats, 12 goats were randomly assigned to 1 of 2 groups: the LPS-treated group (60 ?g/kg BW of LPS; jugular vein injections) or the control group (saline vehicle; jugular vein injections). Blood samples were collected from jugular veins at 0, 1, 2, 4, 6, and 8 h, and liver tissue samples were biopsied 8 h after the injections. The dynamic changes in blood glucose levels as well as key hepatic gluconeogenic enzyme mRNA and protein expression, ATP and ADP levels, and glutathione reductase (GR) activity were determined. The results showed that blood glucose levels in the LPS group were dramatically reduced after an initial, short-term increase. In liver tissue, the mRNA of key gluconeogenic enzymes, phosphoenolpyruvate carboxykinase 1 (PEPCK1; < 0.05), fructose-1,6-bisphosphatase 1 (FBP1; < 0.01), pyruvate carboxylase (PCB; < 0.05), and acyl-CoA synthetase short-chain family member 3 (ACSS3; < 0.01), in the related pathways and PPAR-? coactivator 1? (PGC-1?; < 0.05) were decreased in the LPS group compared with those in the control group, whereas glucose-6-phosphatase (G6Pase-?) was not different ( > 0.05). The protein expression of PEPCK1 decreased ( < 0.01), whereas that of G6Pase-? increased ( < 0.05) significantly. The ratio of ADP to ATP ( < 0.05) and the activity of GR ( < 0.01) were markedly increased in the LPS group compared with those in controls. This research showed that LPS markedly affects and reduces blood glucose in dairy goats. The crucial reasons for the marked change in blood glucose are the altered expression of key gluconeogenic enzymes in different pathways and of essential factors associated with gluconeogenesis in the liver. PMID:26115264

  18. Acute and fulminant hepatitis induced by flutamide: case series report and review of the literature.

    PubMed

    Brahm, Javier; Brahm, Magdalena; Segovia, Roberto; Latorre, Ricardo; Zapata, Rodrigo; Poniachik, Jaime; Buckel, Erwin; Contreras, Luis

    2011-01-01

    Flutamide is a non-steroidal anti-androgenic drug, commonly used in the treatment of advanced prostate cancer, acne and hirsutism. This drug may induce various degrees of liver injury, including acute liver failure (ALF), with further need for liver transplantation. Here, we present a report of 10 consecutive patients seen in a period of 14 years, with acute liver toxicity induced by flutamide (in most cases severe hepatotoxicity): 3 men and 7 women, with a mean age of 75 and 29 years old, respectively. All men received flutamide as treatment of advanced prostate carcinoma and they developed hepatotoxicity without ALF, and three months after withdrawal of the drug, they recovered completely. In contrast, in 7 young female with liver toxicity caused by flutamide as treatment of various hyperandrogenic conditions (acne and hirsutism), ALF was observed in 5 patients, all of them requiring urgent liver transplantation, with excellent outcome and survival in 4 of them. Based on the above, we believe that flutamide treatment should be preferentially avoided in young female patients with benign pathologies, or if it is used, patients should be warned of its potential severe complications. Also, serial liver tests should be closely monitored and, in case of elevations, the drug should be immediately withdrawn. PMID:21301018

  19. Acute intravenous toxicity of dimethyl sulfoxide, polyethylene glycol 400, dimethylformamide, absolute ethanol, and benzyl alcohol in inbred mouse strains.

    PubMed

    Montaguti, P; Melloni, E; Cavalletti, E

    1994-04-01

    Acute intravenous toxicity of some solvents, i.e. dimethyl sulfoxide (DMSO), polyethylene glycol 400 (PEG 400), dimethylformamide (DMF), absolute ethanol (EtOH) and benzyl alcohol (BeOH), was determined in three inbred (CD2F1, B6D2F1 and C57BL/6N) mouse strains used in many preclinical tests, mainly in oncology and toxicology. Haemolytic and precipitation potential tests in vitro were performed to assess the blood compatibility of the investigated solvents and its relationship with the observed symptoms. The single tested solvents did not show any major differences in acute toxicity in the three tested strains with the exclusion of DMSO (less toxic in CD2F1) and BeOH and EtOH (less toxic in B6D2F1). The tested dose ranges in the three strains (in ml/kg) were 1.0-5.66 for DMSO, 2.0-8.0 for PEG 400, 1.0-4.0 for DMF, 0.75-4.24 for EtOH, 0.025-0.4 for BeOH. The lowest tested dose was a safe dose and the highest one was the dose causing mortality in no more than half the animals in each group. The in vitro results suggest avoiding the use of BeOH (which also is more toxic than the other solvents in the in vivo test) and DMSO and using PEG400, EtOH and DMF even though the latter induced a body weight decrease in the B6D2F1 mouse strain. As a general conclusion, dilution of these solvents in water is suggested to ameliorate their blood compatibility and the use of doses not higher than the lowest dose tested in this study is recommended. PMID:8011014

  20. Acute alcohol exposure has an independent impact on C-reactive protein levels, neutrophil CD64 expression, and subsets of circulating white blood cells differentiated by flow cytometry in nontrauma patients.

    PubMed

    Gacouin, Arnaud; Roussel, Mikael; Le Priol, Jerome; Azzaoui, Imane; Uhel, Fabrice; Fest, Thierry; Le Tulzo, Yves; Tadie, Jean Marc

    2014-09-01

    Acute and massive alcohol exposure (blood alcohol concentration of ?1 g/L) is a common way to consume alcohol. In a prospective study performed in critically ill nontrauma patients, we compared C-reactive protein (CRP) values, circulating subsets of white blood cells, and neutrophil CD64 indexes recorded at admission to the intensive care unit between abstinent or moderate drinkers (n = 173), patients with acute or chronic alcohol exposure (n = 32), and patients with acute exposure but not chronically exposed to alcohol (n = 27). Values for CRP (P < 0.001), circulating neutrophils (P < 0.001), and neutrophil CD64 indexes (P < 0.001) were significantly lower in patients acutely exposed compared with the other patients, whereas values for B lymphocytes (P < 0.001) and cytotoxic (P < 0.001) and noncytotoxic T lymphocytes (P < 0.001) were significantly higher. After multiple regression analysis, alcohol exposure remained independently associated with values of CRP, neutrophils CD4 indexes, cytotoxic and noncytotoxic T lymphocytes, and CD16-negative and -positive monocytes. These results were not affected by the presence or absence of infection at admission. Our results suggest that in nontrauma critically ill patients, acute alcohol exposure diminishes inflammation and increases numbers of circulating B and T lymphocytes. PMID:24827394

  1. Problematic Internet use, excessive alcohol consumption, their comorbidity and cardiovascular and cortisol reactions to acute psychological stress in a student population.

    PubMed

    Bibbey, Adam; Phillips, Anna C; Ginty, Annie T; Carroll, Douglas

    2015-06-01

    Background and aims Problematic Internet use and excessive alcohol consumption have been associated with a host of maladaptive outcomes. Further, low (blunted) cardiovascular and stress hormone (e.g. cortisol) reactions to acute psychological stress are a feature of individuals with a range of adverse health and behavioural characteristics, including dependencies such as tobacco and alcohol addiction. The present study extended this research by examining whether behavioural dependencies, namely problematic Internet use, excessive alcohol consumption, and their comorbidity would also be associated with blunted stress reactivity Methods A large sample of university students (N = 2313) were screened using Internet and alcohol dependency questionnaires to select four groups for laboratory testing: comorbid Internet and alcohol dependence (N = 17), Internet dependence (N = 17), alcohol dependence (N = 28), and non-dependent controls (N = 26). Cardiovascular activity and salivary cortisol were measured at rest and in response to a psychological stress protocol comprising of mental arithmetic and public speaking tasks. Results Neither problematic Internet behaviour nor excessive alcohol consumption, either individually or in combination, were associated with blunted cardiovascular or cortisol stress reactions. Discussion It is possible that problematic Internet behaviour and excessive alcohol consumption in a student population were not related to physiological reactivity as they may not reflect ingrained addictions but rather an impulse control disorder and binging tendency. Conclusions The present results serve to indicate some of the limits of the developing hypothesis that blunted stress reactivity is a peripheral marker of the central motivational dysregulation in the brain underpinning a wide range of health and behavioural problems. PMID:26014670

  2. Detection of mixed populations of wild-type and YMDD hepatitis B variants by pyrosequencing in acutely and chronically infected patients

    PubMed Central

    2012-01-01

    Background Lamivudine (LAM) is associated with the highest known rate of resistance mutations among nucleotide analogs used to treat chronic hepatitis B virus (HBV) infection. Despite this, LAM continues in widespread use, especially in combination therapies. The primary LAM resistance mutation (rtM204V/I) occurs in the YMDD motif of HBV polymerase. The aim of this study was to characterize Brazilian HBV isolates from acute and chronic cases by direct sequencing, and to identify HBV quasispecies in the YMDD motif using a pyrosequencing method capable of detecting single-nucleotide polymorphisms. HBV DNA from serum samples of 20 individuals with acute HBV infection and 44 with chronic infection undergoing antiviral therapies containing LAM were analyzed by direct sequencing and pyrosequencing methods. Results Phylogenic analyses of direct-sequenced isolates showed the expected genotypes (A, D and F) for the Brazilian population in both acute and chronic infections. However, within genotype A isolates, subgenotype A2 was more frequently detected in acute cases than in chronic cases (P?=?0.012). As expected, none of the individuals with acute hepatitis B had LAM-resistant isolates as a dominant virus population, whether detected by direct sequencing or pyrosequencing. However, pyrosequencing analyses showed that 45% of isolates (9/20) had minor subpopulations (4-17%) of LAM-resistant isolates. Among chronic patients undergoing LAM treatment, YMDD mutants were frequently found as a dominant virus population. In cases where wild-type virus was the dominant population, subpopulations of YMDD variants were usually found, demonstrating the complexity of HBV quasispecies. Conclusions YMDD variants were frequently detected as a minor population in acute HBV infection. The occurrence of pre-existing variants may lead to a high frequency of resistant mutants during antiviral therapy in the chronic phase. In chronic infection, detection of YMDD variants before virological or biochemical breakthrough might contribute to making better therapy choices and thus improving treatment outcome. PMID:22672436

  3. The inhibitory effect of black soybean on hepatic cholesterol accumulation in high cholesterol and high fat diet-induced non-alcoholic fatty liver disease.

    PubMed

    Jung, Ji-Hye; Kim, Hyun-Sook

    2013-10-01

    Non-alcoholic fatty liver disease (NAFLD) is defined as excess of fat in the liver. We investigated the effects of black soybean on the cholesterol metabolism and insulin resistance of mice fed high cholesterol/fat diets. Mice were randomly allocated into four groups that were fed different diets: the normal cholesterol/fat diet; high cholesterol/fat diets (HCD); and HCD with 1%, and 4% black soybean powder (1B-HCD, and 4B-HCD). Liver total cholesterol and triglyceride concentrations were significantly lower in the black soybean-supplemented groups than that in the HCD group. PCR revealed significantly lower hepatic SREBP2 and HMG-CoA reductase mRNA levels of black soybean-supplemented mice. Real-time PCR revealed significantly higher hepatic ABCA1 mRNA level of black soybean-supplemented mice, which may increase cholesterol efflux. Liver bile acids concentration was significantly high in the 4B-HCD group. Black soybean stimulated secretion of adiponectin, activation of pAMPK, and eliminated free fatty acids in the liver. Black soybean supplementation decreased MDA and nitrate level. The activities of SOD, catalase, and GPx were restored by black soybean supplementation. Our data strongly indicate that black soybean influences the balance between oxidative and antioxidative stress. We suggest that black soybean improves cholesterol metabolism, insulin resistance, and alleviates oxidative damage in NAFLD. PMID:23900008

  4. Acute Alcohol Consumption and Secondary Psychopathic Traits Increase Ratings of the Attractiveness and Health of Ethnic Ingroup Faces but Not Outgroup Faces

    PubMed Central

    Mitchell, Ian J.; Gillespie, Steven M.; Leverton, Monica; Llewellyn, Victoria; Neale, Emily; Stevenson, Isobel

    2015-01-01

    Studies have consistently shown that both consumption of acute amounts of alcohol and elevated antisocial psychopathic traits are associated with an impaired ability for prepotent response inhibition. This may manifest as a reduced ability to inhibit prepotent race biased responses. Here, we tested the effects of acute alcohol consumption, and elevated antisocial psychopathic traits, on judgments of the attractiveness and health of ethnic ingroup and outgroup faces. In the first study, we show that following acute alcohol consumption, at a dose that is sufficient to result in impaired performance on tests of executive function, Caucasian participants judged White faces to be more attractive and healthier compared to when sober. However, this effect did not extend to Black faces. A similar effect was found in a second study involving sober Caucasian participants where secondary psychopathic traits were related to an intergroup bias in the ratings of attractiveness for White versus Black faces. These results are discussed in terms of a model which postulates that poor prefrontal functioning leads to increases in ingroup liking as a result of impaired abilities for prepotent response inhibition. PMID:25745403

  5. Alcoholism and Alcohol Abuse

    MedlinePLUS

    ... their drinking causes distress and harm. It includes alcoholism and alcohol abuse. Alcoholism, or alcohol dependence, is a disease that causes ... groups. NIH: National Institute on Alcohol Abuse and Alcoholism

  6. Lycium barbarum polysaccharides therapeutically improve hepatic functions in non-alcoholic steatohepatitis rats and cellular steatosis model

    PubMed Central

    Xiao, Jia; Xing, Feiyue; Huo, Jie; Fung, Man Lung; Liong, Emily C.; Ching, Yick Pang; Xu, Aimin; Chang, Raymond Chuen Chung; So, Kwok Fai; Tipoe, George L.

    2014-01-01

    This study aimed to investigate the possible therapeutic effects and active components of Lycium barbarum polysaccharides (LBP) on a high fat diet-induced NASH rat model. We induced NASH in a rat model by voluntary oral feeding with a high-fat diet ad libitum for 8 weeks. After 8 weeks, 1?mg/kg LBP was orally administered for another 4 weeks with a high-fat diet. When compared with NASH rats treated for 12 weeks, therapeutic LBP treatment for 4 weeks during 12 weeks of NASH induction showed ameliorative effects on: (1) increased body and wet liver weights; (2) insulin resistance and glucose metabolic dysfunction; (3) elevated level of serum aminotransferases; (4) fat accumulation in the liver and increased serum free fatty acid (FFA) level; (5) hepatic fibrosis; (6) hepatic oxidative stress; (7) hepatic inflammatory response; and (8) hepatic apoptosis. These improvements were partially through the modulation of transcription factor NF-?B, MAPK pathways and the autophagic process. In a palmitate acid-induced rat hepatocyte steatosis cell–based model, we also demonstrated that l-arabinose and ?-carotene partially accounted for the beneficial effects of LBP on the hepatocytes. In conclusion, LBP possesses a variety of hepato-protective properties which make it a potent supplementary therapeutic agent against NASH in future clinical trials. PMID:24998389

  7. The nuclear receptor CAR modulates alcohol-induced liver injury.

    PubMed

    Chen, Xiaosong; Meng, Zhipeng; Wang, Xiaoqiong; Zeng, Samuel; Huang, Wendong

    2011-08-01

    The constitutive androstane receptor (CAR) is a member of the nuclear receptor superfamily and a sensor and detoxifier of both xenobiotics and endobiotics. Recent studies also show that CAR participates in metabolism of glucose and lipid, and has an important role in fatty liver disease and diabetes. In this study, we investigate the roles of CAR in chronic and acute alcohol-induced liver injuries. The results showed that absence of CAR in rodents led to significantly increased susceptibility to chronic alcohol-induced liver injury, which was accompanied with elevated hepatocyte apoptosis and fat accumulation. However, pre-activation of CAR by a CAR agonist, TCPOBOP, strongly enhanced the hepatic toxicity by both chronic and acute alcohol infusion in wild-type, but not in CAR(-/-) mice. Gene expression analyses indicated that CAR pre-activation and alcohol infusion synergistically decreased the expression of enzymes that metabolize the alcohol in liver. These results support a role of CAR in modulating alcoholic liver injury and imply a risk of synergistic liver toxicity induced by alcohol and CAR activation. PMID:21519326

  8. GPS2-dependent corepressor/SUMO pathways govern anti-inflammatory actions of LRH-1 and LXR? in the hepatic acute phase response

    PubMed Central

    Venteclef, Nicolas; Jakobsson, Tomas; Ehrlund, Anna; Damdimopoulos, Anastasios; Mikkonen, Laura; Ellis, Ewa; Nilsson, Lisa-Mari; Parini, Paolo; Jänne, Olli A.; Gustafsson, Jan-Åke; Steffensen, Knut R.; Treuter, Eckardt

    2010-01-01

    The orphan receptor LRH-1 and the oxysterol receptors LXR? and LXR? are established transcriptional regulators of lipid metabolism that appear to control inflammatory processes. Here, we investigate the anti-inflammatory actions of these nuclear receptors in the hepatic acute phase response (APR). We report that selective synthetic agonists induce SUMOylation-dependent recruitment of either LRH-1 or LXR to hepatic APR promoters and prevent the clearance of the N-CoR corepressor complex upon cytokine stimulation. Investigations of the APR in vivo, using LXR knockout mice, indicate that the anti-inflammatory actions of LXR agonists are triggered selectively by the LXR? subtype. We further find that hepatic APR responses in small ubiquitin-like modifier-1 (SUMO-1) knockout mice are increased, which is due in part to diminished LRH-1 action at APR promoters. Finally, we provide evidence that the metabolically important coregulator GPS2 functions as a hitherto unrecognized transrepression mediator of interactions between SUMOylated nuclear receptors and the N-CoR corepressor complex. Our study extends the knowledge of anti-inflammatory mechanisms and pathways directed by metabolic nuclear receptor–corepressor networks to the control of the hepatic APR, and implies alternative pharmacological strategies for the treatment of human metabolic diseases associated with inflammation. PMID:20159957

  9. Hepatic Deletion of Smad7 in Mouse Leads to Spontaneous Liver Dysfunction and Aggravates Alcoholic Liver Injury

    PubMed Central

    Zhu, Lu; Wang, Lingdi; Wang, Xiao; Luo, Xiaolin; Yang, Ling; Zhang, Rui; Yin, Hongkun; Xie, Dong; Pan, Yi; Chen, Yan

    2011-01-01

    Background TGF-? has been known to play an important role in various liver diseases including fibrosis and alcohol-induced fatty liver. Smad7 is an intracellular negative regulator of TGF-? signaling. It is currently unclear whether endogenous Smad7 has an effect on liver function and alcoholic liver damage. Methodology/Principal Findings We used Cre/loxP system by crossing Alb-Cre mice with Smad7loxP/loxP mice to generate liver-specific deletion of Smad7 with loss of the indispensable MH2 domain. Alcoholic liver injury was achieved by feeding mice with a liquid diet containing 5% ethanol for 6 weeks, followed by a single dose of ethanol gavage. Deletion of Smad7 in the liver was associated with increased Smad2/3 phosphorylation in the liver or upon TGF-? treatment in primary hepatocytes. The majority of mice with liver specific deletion of Smad7 (Smad7liver-KO) were viable and phenotypically normal, accompanied by only slight or no reduction of Smad7 expression in the liver. However, about 30% of Smad7liver-KO mice with high efficiency of Smad7 deletion had spontaneous liver dysfunction, demonstrated as low body weight, overall deterioration, and increased serum levels of AST and ALT. Degeneration and elevated apoptosis of liver cells were observed with these mice. TGF-?-induced epithelial to mesenchymal transition (EMT) was accelerated in Smad7-deleted primary hepatocytes. In addition, alcohol-induced liver injury and steatosis were profoundly aggravated in Smad7 deficient mice, associated with upregulation of critical genes involved in lipogenesis and inflammation. Furthermore, alcohol-induced ADH1 expression was significantly abrogated by Smad7 deletion in hepatocytes. Conclusion/Significance In this study, we provided in vivo evidence revealing that endogenous Smad7 plays an important role in liver function and alcohol-induced liver injury. PMID:21386907

  10. The Effects of Acute Alcohol Consumption, Cognitive Reserve, Partner Risk, and Gender on Sexual Decision Making*

    PubMed Central

    Abbey, Antonia; Saenz, Christopher; Buck, Philip O.; Parkhill, Michele R.; Hayman, Lenwood W.

    2015-01-01

    Objective In past alcohol administration studies, intoxicated college students have been more willing to have unprotected sex with a hypothetical new partner than sober or placebo students. The objective of the present research was to extend past work by examining the effects of gender, cognitive reserve, and partner risk on intoxicated sexual decision making. Method Before assigning participants (60 women and 60 men) to a drink condition, cognitive reserve was assessed with the reading subtest of the Wide Range Achievement Test 3 (WRAT3). After drinking, participants watched a video of a male and female college student in a sexual situation. There were two versions of the video that were identical, except for information that suggested the opposite-gender character had many past sexual partners or only a few. Results There was a significant interaction between drink condition and cognitive reserve such that intoxicated participants with lower WRAT3 scores were more likely than other participants to indicate that they would have unprotected sex if they were in this situation. Partner risk did not influence participants' willingness to have unprotected sex; however, they were less interested in dating the high-risk partner. Conclusions As expected, participants with less cognitive reserve made riskier decisions when intoxicated. Unexpectedly, although participants clearly perceived the high- and low-risk partners differently, this did not affect their willingness to have unprotected sex with this hypothetical partner. These findings demonstrate the need for sexually transmitted disease/ HIV prevention programs that go beyond factual presentations and provide students with the skills they need to assess risk realistically and the need for programs with messages tailored for individuals with low cognitive skills. PMID:16536135

  11. Pathogenesis of Hepatic Encephalopathy and Brain Edema in Acute Liver Failure

    PubMed Central

    Butterworth, Roger F.

    2014-01-01

    Neuropathologic investigations in acute liver failure (ALF) reveal significant alterations to neuroglia consisting of swelling of astrocytes leading to cytotoxic brain edema and intracranial hypertension as well as activation of microglia indicative of a central neuroinflammatory response. Increased arterial ammonia concentrations in patients with ALF are predictors of patients at risk for the development of brain herniation. Molecular and spectroscopic techniques in ALF reveal alterations in expression of an array of genes coding for neuroglial proteins involved in cell volume regulation and mitochondrial function as well as in the transport of neurotransmitter amino acids and in the synthesis of pro-inflammatory cytokines. Liver-brain pro-inflammatory signaling mechanisms involving transduction of systemically-derived cytokines, ammonia neurotoxicity and exposure to increased brain lactate have been proposed. Mild hypothermia and N-Acetyl cysteine have both hepato-protective and neuro-protective properties in ALF. Potentially effective anti-inflammatory agents aimed at control of encephalopathy and brain edema in ALF include etanercept and the antibiotic minocycline, a potent inhibitor of microglial activation. Translation of these potentially-interesting findings to the clinic is anxiously awaited.

  12. Manifestations of Perihepatic Lymph Nodes in Acute Flare of Chronic Hepatitis B: Association with HBeAg Status and with HBeAg Seroconversion

    PubMed Central

    Ko, Yen-Ling; Sun, Chi-Shu; Chung, Kun-Ming; Lin, Yu-Min; Feng, I-Che; Sheu, Ming-Jen; Koay, Lok-Beng; Lin, Ching-Yih; Ho, Chung-Han; Kuo, Hsing-Tao

    2015-01-01

    It has been observed that enlargement of perihepatic lymph nodes may be seen in patients with chronic hepatitis B, particularly during acute flares of CHB. We hypothesized that there may be a correlation between the nodal change patterns in CHB patients with acute flare and HBeAg status. Perihepatic lymph node sizes of 87 patients with acute flares of CHB were documented, with a median follow up of 43 months. Patients were separated into 3 groups, HBeAg-positive with HBe seroconversion (group 1), HBeAg-positive without HBe seroconversion (group 2), and HBeAg-negative (group 3). Group 1 has the highest incidence of enlarged lymph nodes (92.3%) compared with group 2 (75.8%) and group 3 (46.8%) (p = 0.003). And if nodal width at acute flare was > 8mm and interval change of nodal width was >3mm, the incidence of HBeAg seroconversion will be 75% (p<0.001). Conclusion Larger perihepatic lymph nodes are seen in CHB acute flare patients with positive HBeAg and the magnitude of nodal width change may predict HBeAg seroconversion at recovery. PMID:25689069

  13. Hypertonic saline resuscitation enhances blood pressure recovery and decreases organ injury following hemorrhage in acute alcohol intoxicated rodents

    PubMed Central

    Sulzer, Jesse K.; Whitaker, Annie M.; Molina, Patricia E.

    2012-01-01

    Background Acute alcohol intoxication (AAI) impairs the hemodynamic and arginine vasopressin (AVP) counter-regulation to hemorrhagic shock (HS) and lactated Ringer’s (LR) fluid resuscitation (FR). The mechanism of AAI-induced suppression of AVP release in response to HS involves accentuated nitric oxide (NO) inhibitory tone. In contrast, AAI does not prevent AVP response to increased osmolarity produced by hypertonic saline (HTS) infusion. We hypothesized that FR with HTS during AAI would enhance AVP release by decreasing PVN NO inhibitory tone subsequently improving mean arterial blood pressure (MABP) and organ perfusion. Methods Male Sprague Dawley rats received a 15h alcohol infusion (2.5g/kg + 0.3 g/kg/h) or dextrose (DEX) prior to HS (40mmHg × 60 min) and FR with HTS (7.5%; 4ml/kg) or LR (2.4 × blood volume removed). Organ blood flow was determined and brains collected for NO content at 2h post-FR. Results HTS improved MABP recovery in AAI (109 vs 80mmHg) and DEX (114 vs 83mmHg) animals compared to LR. This was associated with higher (>60%) circulating AVP levels at 2h post-FR than those detected in LR animals in both groups. Neither AAI alone nor HS in DEX animals resuscitated with LR altered organ blood flow. In AAI animals, HS and FR with LR reduced blood flow to liver (72%), small intestine (65%), and large intestine (67%) compared to shams. FR with HTS improved liver (3-fold) and small intestine (2-fold) blood flow compared to LR in AAI-HS animals. The enhanced MABP response to HTS was prevented by pretreatment with a systemic AVP V1a receptor antagonist. HTS decreased PVN NO content in both groups 2h post-FR. Conclusions These results suggest that FR with HTS in AAI results in removal of central NO inhibition of AVP, restoring AVP levels and improving MABP and organ perfusion in AAI-HS. PMID:23147176

  14. Seven Novel Mutations in Bulgarian Patients with Acute Hepatic Porphyrias (AHP).

    PubMed

    Dragneva, Sonya; Szyszka-Niagolov, Monika; Ivanova, Aneta; Mateva, Lyudmila; Izumi, Rumiko; Aoki, Yoko; Matsubara, Yoichi

    2014-01-01

    Acute intermittent porphyria (AIP), variegate porphyria (VP), and hereditary coproporphyria (HCP) are caused by mutations in the hydroxymethylbilane synthase (HMBS), protoporphyrinogen oxidase (PPOX), and coproporphyrinogen oxidase (CPOX) genes, respectively. This study aimed to identify mutations in seven Bulgarian families with AIP, six with VP, and one with HCP. A total of 33 subjects, both symptomatic (n?=?21) and asymptomatic (n?=?12), were included in this study. The identification of mutations was performed by direct sequencing of all the coding exons of the corresponding enzymes in the probands. The available relatives were screened for the possible mutations. A total of six different mutations in HMBS were detected in all seven families with AIP, three of which were previously described: c.76C>T [p.R26C] in exon 3, c.287C>T [p.S96F] in exon 7, and c.445C>T [p.R149X] in exon 9. The following three novel HMBS mutations were found: c.345-2A>C in intron 7-8, c.279-280insAT in exon 7, and c.887delC in exon 15. A total of three different novel mutations were identified in the PPOX gene in the VP families: c.441-442delCA in exon 5, c.917T>C [p.L306P] in exon 9, and c.1252T>C [p.C418R] in exon 12. A novel nonsense mutation, c.364G>T [p.E122X], in exon 1 of the CPOX gene was identified in the HCP family. This study, which identified mutations in Bulgarian families with AHP for the first time, established seven novel mutation sites. Seven latent carriers were also diagnosed and, therefore, were able to receive crucial counseling to prevent attacks. PMID:24997713

  15. Early detection of anti-HCc antibody in acute hepatitis C virus (HCV) by western blot (immunoblot) using a recombinant HCV core protein fragment.

    PubMed Central

    Yeh, C T; Han, C M; Lo, S Y; Ou, J H; Fan, K D; Sheen, I S; Chu, C M; Liaw, Y F

    1994-01-01

    Crude extract from Escherichia coli which expressed a recombinant protein containing amino acids 2 to 127 of the hepatitis C virus (HCV) core protein was used to detect the antibody against HCV core protein (anti-HCc). After electrophoretic separation of proteins from the extract, Western blot (immunoblot) analysis was performed with the serum samples. This method was compared with a commercially available second-generation enzyme immunoassay (EIA) which employed synthetic peptides corresponding to highly antigenic segments of both structural and nonstructural portions of HCV. Also, reverse transcription PCR for HCV RNA was used for comparison. Seventy-two serum samples from three groups of patients were tested. Groups I and II represented healthy subjects and subjects with acute hepatitis A or B, respectively. Group III included patients with newly acquired acute hepatitis C. By Western blot analysis, 31 of 31 (100%) samples from group I were negative for anti-HCc antibody, whereas 4 of 22 (18%) samples from group II were positive for anti-HCc. One of these four samples was also positive for anti-HCV antibody by the second-generation EIA (1 of 22 [4.5%]). Among 19 patients diagnosed with newly acquired acute hepatitis C, 4 (21%) were positive for anti-HCV by the second-generation EIA, whereas 12 of 19 (63%) were positive for anti-HCc by Western blot analysis. Of EIA-positive subjects, 4 of 4 (100%) were also positive for anti-HCc by Western blot analysis, whereas among EIA-negative subjects, 8 of 15 (53%) were positive. For HCV RNA detected by reverse transcription PCR, 15 of 19 (80%) of this group of samples were positive. Strikingly, the peak bilirubin level for patients with EIA-negative and Western blot-positive results is significantly higher than that for patients with consistent EIA and Western blot results (22.7 versus 7.2 mg/dl). A series of serum samples from a patient with concurrent hepatitis B and C viral infection was also studied by both tests. Although anti-HCc persisted throughout the course of infection, anti-HCV by EIA converted from negative to positive 20 days after admission and then converted back to negative 30 days later. Images PMID:7529251

  16. Risk factors for acute non-A, non-B hepatitis and their relationship to antibodies for hepatitis C virus: a case-control study.

    PubMed Central

    Mele, A; Sagliocca, L; Manzillo, G; Converti, F; Amoroso, P; Stazi, M A; Ferrigno, L; Rapicetta, M; Franco, E; Adamo, B

    1994-01-01

    A case-control study was carried out comparing 333 case subjects with non-A, non-B hepatitis and 1095 hospital control subjects. Of 333 case subjects, 197 (59%) were positive for hepatitis C antibody (anti-HCV). Excluding blood transfusion and intravenous drug use, surgical intervention and dental therapy were strongly associated with anti-HCV-positive cases: in particular, obstetric and gynecology surgical intervention was found to be strongly associated with HCV positivity (odds ratio [OR] = 32; 95% confidence interval [CI] = 7, 147). Raw shellfish consumption was a risk factor for anti-HCV-negative cases (OR = 2.2; 95% CI = 1.0, 5.1), thus suggesting an enterically transmitted virus in sporadic non-A, non-B hepatitis in Italy. PMID:7943485

  17. Evaluation of SSYA10-001 as a replication inhibitor of severe acute respiratory syndrome, mouse hepatitis, and Middle East respiratory syndrome coronaviruses.

    PubMed

    Adedeji, Adeyemi O; Singh, Kamalendra; Kassim, Ademola; Coleman, Christopher M; Elliott, Ruth; Weiss, Susan R; Frieman, Matthew B; Sarafianos, Stefan G

    2014-08-01

    We have previously shown that SSYA10-001 blocks severe acute respiratory syndrome coronavirus (SARS-CoV) replication by inhibiting SARS-CoV helicase (nsp13). Here, we show that SSYA10-001 also inhibits replication of two other coronaviruses, mouse hepatitis virus (MHV) and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). A putative binding pocket for SSYA10-001 was identified and shown to be similar in SARS-CoV, MERS-CoV, and MHV helicases. These studies show that it is possible to target multiple coronaviruses through broad-spectrum inhibitors. PMID:24841268

  18. Metabolic syndrome and hepatic resection: improving outcome

    PubMed Central

    Agrawal, Shefali; Daruwala, Cherag

    2011-01-01

    Objective A review of the peri-operative risk associated with hepatic resection in patients with metabolic syndrome (MetS) and identification of measures for the improvement of cardiometabolic disturbances and liver-related mortality. Background MetS and its hepatic manifestation non-alcoholic fatty liver disease (NAFLD) are associated with an increased operative mortality in spite of a significant improvement in peri-operative outcome after hepatic resection. Methods A review of the English literature on MetS, liver resection and steatosis was performed from 1980 to 2011 using the MEDLINE and PubMed databases. Results MetS is a predictor of NAFLD and patients with multiple metabolic risk factors may harbour non-alcoholic steatohepatitis (NASH) predictive of operative and cardiovascular mortality. Pre-operative diagnosis of unsuspected NASH with the selective use of a liver biopsy can modify the operative strategy by limiting the extent of hepatic resection, avoiding or altering the pre-operative chemotherapy regimen and the utilization of portal vein embolization. Thiazolidinediones are therapeutic for MetS and NASH and Vitamin E for active NASH; however, their utility in improving the peri-operative outcome after hepatic resection is unknown. A short-term regimen for weight loss improves post-operative patient and liver-related outcomes in patients with >30% steatosis. Cardiovascular disease associated with MetS or NAFLD should be managed aggressively. Peri-operative measures to minimize thrombotic events and acute renal injury secondary to the pro-inflammatory, prothrombotic state of MetS may further improve the outcome. Conclusion Potential candidates for hepatic resection should be screened for MetS as the pre-operative identification of NASH, short-term treatment of significant steatosis, cardiovascular risk assessment and optimization of each component of MetS may improve the peri-operative outcome in this high-risk subset of patients. PMID:22081919

  19. Full-Length Sequences of Six Hepatitis E Virus Isolates of Genotypes III and IV from Patients with Sporadic Acute or Fulminant Hepatitis in Japan

    Microsoft Academic Search

    Kazuaki Takahashi; Jong-Hon Kang; Sachiyo Ohnishi; Kunihiko Hino; Hiroshi Miyakawa; Yuzo Miyakawa; Hiroshi Maekubo; Shunji Mishiro

    2003-01-01

    Objective: Ranges of variation and conservation in sequence need to be defined for detecting and genotyping hepatitis E virus (HEV). Methods: Six HEV isolates from Japanese patients were sequenced over the entire genome and compared phylogenetically along with 16 reported HEV isolates, including two from pigs. Results: Three of the six HEV isolates were of genotype III, and the remaining

  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. Severe drug induced acute hepatitis associated with use of St John’s wort (Hypericum perforatum) during treatment with pegylated interferon ?

    PubMed Central

    Piccolo, Paola; Gentile, Silvia; Alegiani, Filippo; Angelico, Mario

    2009-01-01

    A 61-year-old woman with chronic hepatitis C received peginterferon ? 180 ?g/week, and obtained undetectable qualitative hepatitis C virus (HCV) RNA (lower limit of detection 50 IU/ml) after 8 weeks of treatment. Shortly thereafter aminotransferase values greatly increased (>20 × upper limit of normal) and did not decline after treatment suspension. The patient admitted taking St John’s wort (Hypericum perforatum) for depressed mood, recommended by a friend, during the preceding 6 weeks. Liver function tests continued to worsen and international normalised ratio (INR) prolongation developed; the patient was hospitalised. Test for antinuclear antibody was positive (1:320) and treatment with methylprednisolone was started; bilirubin and aminotransferase levels slowly declined, though a new flare occurred when steroids were tapered. After 6 months of prednisone treatment, the liver function tests returned to baseline levels. The combination of peginterferon ? and St John’s wort resulted in a severe acute hepatitis in this patient. Patients should be advised of this potential toxic effect of this herbal remedy. PMID:21686643

  2. Curative Effects of Thiacremonone against Acetaminophen-Induced Acute Hepatic Failure via Inhibition of Proinflammatory Cytokines Production and Infiltration of Cytotoxic Immune Cells and Kupffer Cells

    PubMed Central

    Kim, Yu Ri; Ban, Jung Ok; Yoo, Hwan Soo; Lee, Yong Moon; Yoon, Yeo Pyo; Eum, So Young; Jeong, Heon Sang; Yoon, Do-young; Han, Sang Bae; Hong, Jin Tae

    2013-01-01

    High doses of acetaminophen (APAP; N-acetyl-p-aminophenol) cause severe hepatotoxicity after metabolic activation by cytochrome P450 2E1. This study was undertaken to examine the preventive effects of thiacremonone, a compound extracted from garlic, on APAP-induced acute hepatic failure in male C57BL/6J. Mice received with 500?mg/kg APAP after a 7-day pretreatment with thiacremonone (10–50?mg/kg). Thiacremonone inhibited the APAP-induced serum ALT and AST levels in a dose-dependent manner, and markedly reduced the restricted area of necrosis and inflammation by administration of APAP. Thiacremonone also inhibited the APAP-induced depletion of intracellular GSH, induction of nitric oxide, and lipid peroxidation as well as expression of P450 2E1. After APAP injection, the numbers of Kupffer cells, natural killer cells, and cytotoxic T cells were elevated, but the elevated cell numbers in the liver were reduced in thiacremonone pretreated mice. The expression levels of I-309, M-CSF, MIG, MIP-1?, MIP-1?, IL-7, and IL-17 were increased by APAP treatment, which were inhibited in thiacremonone pretreated mice. These data indicate that thiacremonone could be a useful agent for the treatment of drug-induced hepatic failure and that the reduction of cytotoxic immune cells as well as proinflammatory cytokine production may be critical for the prevention of APAP-induced acute liver toxicity. PMID:23935693

  3. The Hepatitis E Virus ORF3 Protein Modulates Epidermal Growth Factor Receptor Trafficking, STAT3 Translocation, and the Acute-Phase Response?

    PubMed Central

    Chandra, Vivek; Kar-Roy, Anindita; Kumari, Sudha; Mayor, Satyajit; Jameel, Shahid

    2008-01-01

    The hepatitis E virus (HEV) causes acute viral hepatitis, but its characterization is hampered by the lack of an efficient in vitro infection system that can be used to study the effects of HEV proteins on cellular processes. Previous studies suggest that the viral ORF3 protein (pORF3) is essential for infection in vivo and is likely to modulate the host response. Here, we report that pORF3 localizes to early and recycling endosomes and causes a delay in the postinternalization trafficking of epidermal growth factor receptor (EGFR) to late endosomes/lysosomes. The cytoplasmic phosphorylated signal transducer and activator of transcription 3 (pSTAT3) proteins require growth factor receptor endocytosis for their translocation from the cytoplasm to nucleus. Consequently, lower levels of pSTAT3 were found in the nuclei of ORF3-expressing Huh7 human hepatoma cells stimulated with EGF. This results in downregulation of the acute-phase response, a major determinant of inflammation in the host. We propose that through its effects on EGFR trafficking, pORF3 prolongs endomembrane growth factor signaling and promotes cell survival. The effects on STAT3 translocation would result in a reduced inflammatory response. Both of these events are likely to contribute positively to viral replication. PMID:18448545

  4. Two Distinct Subtypes of Hepatitis B Virus-Related Acute Liver Failure Are Separable By Quantitative Serum IgM anti-HBc and HBV DNA Levels

    PubMed Central

    Dao, Doan Y; Hynan, Linda S.; Yuan, He-Jun; Sanders, Corron; Balko, Jody; Attar, Nahid; Lok, Anna S.F.; Word, R. Ann; Lee, William M.

    2011-01-01

    Background Hepatitis B virus-related acute liver failure (HBV-ALF) may occur following acute HBV infection (AHBV-ALF) or during an exacerbation of chronic HBV infection (CHBV-ALF). Clinical differentiation of the two is often difficult if a prior history of hepatitis B is not available. Quantitative measurements of anti-hepatitis B core immunoglobulin M (IgM anti-HBc) titers and of HBV viral loads (VLs) might allow separation of acute from chronic HBV-ALF. Methods Of 1602 patients with ALF, 60 met clinical criteria for AHBV-ALF and 27 for CHBV-ALF. Sera were available on 47 and 23 patients, respectively. A quantitative immunoassay was used to determine IgM anti-HBc levels, and real-time polymerase chain reaction (rtPCR) to determine HBV VLs. Results AHBV-ALFs had much higher IgM anti-HBc titers than CHBV-ALFs, (signal to noise (S/N) ratio median 88.5, range 0–1,120, vs. 1.3, 0–750, p<0.001); a cut point for S/N ratio of 5.0 correctly identified 44/46 (96%) AHBV-ALFs and 16/23 (70%) CHBV-ALFs; the area under the receiver operator characteristic curve was 0.86, p<0.001. AHBV-ALF median admission VL was 3.9 (0–8.1) log10 IU/mL, vs. 5.2 (2.0–8.7) log10 IU/mL for CHBV-ALF, p<0.025. Twenty percent (12/60) of the AHBV-ALF group had no hepatitis B surface antigen (HBsAg) detectable on admission to study, while no CHBV-ALF patients experienced HBsAg clearance. Rates of transplant-free survival were 33% (20/60) for AHBV-ALF vs. 11% (3/27) for CHBV-ALF, p=0.030. Conclusions AHBV-ALF and CHBV-ALF differ markedly in IgM anti-HBc titers, in HBV VLs and in prognosis, suggesting that the two forms are indeed different entities that might each have a unique pathogenesis. PMID:21987355

  5. Hepatitis E virus: do locally acquired infections in Australia necessitate laboratory testing in acute hepatitis patients with no overseas travel history?

    PubMed Central

    Shrestha, Ashish C.; Faddy, Helen M.; Flower, Robert L. P.; Seed, Clive R.; Keller, Anthony J.

    2015-01-01

    Summary Hepatitis E virus (HEV) is emerging as a global public health threat. Water-borne HEV outbreaks are common in developing countries and are associated with genotypes 1 and 2. In industrialised countries, sporadic cases of zoonotic transmission associated with genotypes 3 and 4 are increasingly being reported. Transfusion- and transplantation-transmitted HEV have been documented, although ingestion of contaminated food is thought to be the major transmission route. Severe disease is possible and chronic hepatitis infection occurs in solid-organ-transplant recipients and in patients with immunosuppressive disorders. In Australia, HEV cases are mainly travellers returning from disease endemic countries. Indeed, there are few reported cases of locally acquired HEV. Pigs in Australia have been shown to be infected with HEV, which indicates the possibility of zoonotic transmission. The extent of locally acquired infection is not known, however it may be greater than expected and may necessitate laboratory testing in patients reporting no overseas travel. PMID:25560836

  6. Role of p38 Mapk in Development of Acute Hepatic Injury in Long-Evans Cinnamon (LEC) Rats, an Animal Model of Human Wilson’s Disease

    PubMed Central

    KADOWAKI, Shingo; MEGURO, Saori; IMAIZUMI, Yoshitaka; SAKAI, Hiroshi; ENDOH, Daiji; HAYASHI, Masanobu

    2013-01-01

    ABSTRACT The Long-Evans Cinnamon (LEC) rat, an animal model of human Wilson’s disease, spontaneously develops fulminant hepatitis associated with severe jaundice at about 4 months of age. In this study, we examined the changes in gene expression during progression of acute hepatic injury. When levels of gene expression in the liver of LEC rats at 13 weeks of age were compared to those in rats at 4 weeks of age using oligonucleotide arrays, 1,620 genes out of 7,700 genes analyzed showed more than 2-fold differences. Expression levels of 11 of 29 genes related to stress-activating protein kinase (SAPK) changed by more than 2-fold in the liver of LEC rats, but none of the SAPK-related genes showed changes in expression levels in the liver of control rats. Activity of p38 mapk in the liver of LEC rats at 13 weeks of age was about 8.1-fold higher than that in rats at 4 weeks of age. When LEC rats were administered SB203580, a p38 mapk-specific inhibitor, by s.c. injection twice a week from 10 to 13 weeks of age, activities of p38 mapk in the liver, activities of AST and ALT and concentrations of bilirubin in sera of rats administered SB203580 significantly decreased compared to those in rats not administered. These results showed that the increase in activities of p38 mapk was related to the occurrence of acute hepatic injury in LEC rats. PMID:23877843

  7. 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

  8. Are oxidative stress mechanisms the common denominator in the progression from hepatic steatosis towards non-alcoholic steatohepatitis (NASH)?

    PubMed

    Tariq, Zoon; Green, Charlotte J; Hodson, Leanne

    2014-08-01

    Non-alcoholic fatty liver disease (NAFLD) is not a single disease entity, rather it describes a spectrum of liver conditions that range from fatty liver (steatosis) to more severe steatosis coupled with marked inflammation and fibrosis [non-alcoholic steatohepatitis (NASH)] to severe liver disease such as cirrhosis and possibly hepatocellular carcinoma. Obesity, notably abdominal obesity, is a common risk factor for NAFLD. The pathogenesis from steatosis to NASH is poorly understood, and the 'two hit' model, as suggested nearly two decades ago, provides a feasible starting point for characterization of underlying mechanisms. This review will examine the oxidative stress factors ('triggers') which have been implicated as a 'second hit' in the development of primary NASH. It would be reasonable to assume that multiple, rather than single, pro-oxidative intracellular and extracellular triggers act in conjunction promoting oxidative stress that drives the development of NASH. It is likely that the common denominator of these pro-oxidative triggers is mitochondrial dysfunction. Understanding the contribution of each of these 'triggers' is an essential step in starting to understand and elucidate the mechanisms responsible for progression from steatosis to NASH, thus enabling the development of therapeutic targeting to prevent NASH development and progression. PMID:24621397

  9. Cellular and humoral immune reactions in chronic active liver disease. II. Lymphocyte subsets and viral antigens in liver biopsies of patients with acute and chronic hepatitis B.

    PubMed Central

    Eggink, H F; Houthoff, H J; Huitema, S; Wolters, G; Poppema, S; Gips, C H

    1984-01-01

    The characteristics and distribution of the inflammatory infiltrate in liver biopsies of 25 patients with hepatitis B viral (HBV) infection were studied in relation to the distribution and expression of HBV antigens. Mononuclear subsets were characterized with monoclonal (OKT, OKM, Leu) antibodies to surface antigens. For the demonstration of viral antigens directly conjugated antibodies to surface (HBsAg), core (HBcAg) and 'e' (HBeAg) antigen were used. For the study of mutual relations all methods were performed on serial cut tissue sections. In chronic active hepatitis B (CAH-B, n = 12) OKT8+ lymphocytes of T cell origin were the only cell type present in areas with liver cell degeneration and T cell cytotoxicity appears to be the only immune mechanism. In chronic persistent hepatitis B (CPH-B, n = 7) the only conspicuous feature was the presence of many Leu 3+ lymphocytes of the helper/inducer population in the portal tracts. In acute hepatitis B (AHB, n = 6) OKT8+ cells of non-T origin (OKT1-,3-) and Leu 7+ cells of presumed natural killer (NK) potential predominated in the areas with liver cell necrosis, and non-T cell cytotoxicity appears to be the predominant immune mechanism. In none of these disease entities a positive spatial relation could be established between the cytotoxic cells and the demonstrable expression of HBV antigens in hepatocytes. It is concluded that differences in immunological reaction pattern may explain the different course in the three forms of HBV infection studied. Images Fig. 1 Fig. 2 PMID:6713726

  10. 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

  11. 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

  12. Alcoholic and non-alcoholic steatohepatitis.

    PubMed

    Neuman, Manuela G; French, Samuel W; French, Barbara A; Seitz, Helmut K; Cohen, Lawrence B; Mueller, Sebastian; Osna, Natalia A; Kharbanda, Kusum K; Seth, Devanshi; Bautista, Abraham; Thompson, Kyle J; McKillop, Iain H; Kirpich, Irina A; McClain, Craig J; Bataller, Ramon; Nanau, Radu M; Voiculescu, Mihai; Opris, Mihai; Shen, Hong; Tillman, Brittany; Li, Jun; Liu, Hui; Thomes, Paul G; Ganesan, Murali; Malnick, Steve

    2014-12-01

    This paper is based upon the "Charles Lieber Satellite Symposia" organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human immunodeficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible repair. We aim to (1) determine the immuno-pathology of alcohol-induced liver damage, (2) examine the role of genetics in the development of ASH, (3) propose diagnostic markers of ASH and NASH, (4) examine age differences, (5) develop common research tools to study alcohol-induced effects in clinical and pre-clinical studies, and (6) focus on factors that aggravate severity of organ-damage. The intention of these symposia is to advance the international profile of the biological research on alcoholism. We also wish to further our mission of leading the forum to progress the science and practice of translational research in alcoholism. PMID:25217800

  13. Acute psychosis due to the interaction of legal compounds--ephedra alkaloids in 'vigueur fit' tablets, caffeine in 'red bull' and alcohol.

    PubMed

    Tormey, W P; Bruzzi, A

    2001-10-01

    A short-lasting episode of acute psychosis in a 32-year-old male which followed the consumption of alcohol, caffeine and 'vigueur fit' tablets containing ephedra alkaloids is reported. Less than two days after the event, a urine sample contained 22 microg/ml of ephedrine and 5 microg/ml of pseudoephedrine. Despite detailed pharmacological evidence being given at a jury trial, he was convicted of assault and trespass and was fined pounds sterling 16,000. An earlier incident involving misbehaviour on an aircraft again involving alcohol and ephedrine resulted in a conviction and a court order to provide twice weekly urine tests for alcohol for a period of six months. He stopped taking the alkaloid tablets after the second incident. There was no history of aberrant behaviour in this man outwith the period when taking these tablets. Ephedra alkaloids may cause psychosis and their effects can be exaggerated by interaction with caffeine and ethanol. To protect the public, the use of stimulant drugs in over-the-counter weight control programmes should be prescription only and the package insert should include a warning on the dangers of concomitant use of ethanol. PMID:11693229

  14. [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

  15. Orlistat-induced fulminant hepatic failure.

    PubMed

    Sall, D; Wang, J; Rashkin, M; Welch, M; Droege, C; Schauer, D

    2014-12-01

    Orlistat was approved by the Food and Drug Administration in 1998 and has been shown to be superior to placebo in achieving weight loss. It is generally well tolerated. However, severe liver injury has been reported. We present a case of hepatic failure in a patient taking orlistat. A 54-year-old African-American woman with hypertension presented with hepatic failure. She had noticed increasing fatigue, jaundice and confusion. She used alcohol sparingly and denied tobacco or illicit drug use, but had been taking over-the-counter orlistat for the past two months. Physical examination revealed scleral icterus, jaundice, asterixis and slow speech. Laboratory testing showed markedly abnormal liver function tests with coagulopathy. Acute viral and autoimmune serologies were negative, as was toxicology screen. Liver biopsy showed necrotic hepatic parenchyma likely secondary to drug toxicity. Based upon her clinical presentation and time course, the pattern of liver injury seen on liver biopsy and lack of an alternative plausible explanation, her liver failure was most likely associated with orlistat use. She continued to deteriorate and ultimately underwent orthotopic liver transplantation. Fourteen cases of severe liver injury associated with orlistat use have been reported, four of which are detailed in the literature. This is the second published case of liver failure associated with over-the-counter orlistat usage. Clinicians should be aware of the growing number of cases associating liver injury and orlistat use and carefully monitor their patients on this medication for signs of hepatic dysfunction. PMID:25826164

  16. 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,

  17. Hepatorenal syndrome: resolution of ascites by continuous renal replacement therapy in an alcoholic coinfected with hepatitis B, C, and human immunodeficiency viruses.

    PubMed

    Hansard, Paul C; Manning, Ricardo A; Haseeb, M A; Salwen, Martin J

    2006-01-01

    A 39-yr-old male with hepatorenal syndrome type 1 and refractory ascites was treated with continuous renal replacement therapy (CRRT) resulting in clinical improvement. He was positive for antibodies to hepatitis B, C, and human immunodeficiency viruses, and had a history of chronic alcohol and iv drug abuse. The patient had 4 hospital admissions during a 12-wk period. He first presented with advanced liver disease including pedal edema and a serum ammonia level of 56 micromol/L (reference range: 11 - 35 micromol/L). In subsequent admissions, he had asterixis, nausea, vomiting, jaundice, and worsening pedal edema. On his 4th admission, there was lethargy, tense ascites, decreased urinary output, bilateral edema of the lower extremities and scrotum, serum creatinine of 6.2 mg/dl (reference range: 0.6 - 1.5 mg/dl), and weight gain of 16 kg during the prior 8 wk. During the first 3 hospitalizations, he was treated with lactulose with slight improvement. On the 4th admission, he was started on low-dose dopamine (3 microg/kg/min) and 25% salt-poor albumin without clinical improvement. A pulmonary artery catheter was placed and hemofiltration by CRRT was performed for 5 days, with removal of 26.7 L of fluid and a net reduction of 11 kg of body weight. Serum creatinine decreased to 4.2 mg/dl during CRRT and was 2.2 mg/dl at hospital discharge 2 weeks later. His PaO(2) improved from 66 to 78 mmHg and his systemic vascular resistance increased from 571 to 799 dyne.sec/cm(5). CRRT was effective in relieving severe fluid retention and producing marked clinical improvement. We suggest that CRRT should be considered for the treatment of refractory ascites including that caused by hepatorenal syndrome. PMID:16501243

  18. Acoustic Radiation Force Impulse Elastography for the Non-Invasive Evaluation of Hepatic Fibrosis in Non-Alcoholic Fatty Liver Disease Patients: A Systematic Review & Meta-Analysis

    PubMed Central

    Liu, Haixia; Fu, Jing; Hong, Ruixia; Liu, Li; Li, Fang

    2015-01-01

    Background In order to better monitor non-alcoholic fatty liver disease (NAFLD) patients at higher risk for HCC, there is a need for non-invasive diagnostic approaches to screen for the presence of advanced fibrosis in these patients. The aim of this systematic review and meta-analysis will be to evaluate the diagnostic efficacy of ARFI elastography in detecting hepatic fibrosis in NAFLD patients. Methods Relevant studies were identified from systematic searches of several major electronic databases (PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials). The primary outcomes were the summary sensitivity, summary specificity, the diagnostic odds ratio, and the summary receiver operating characteristic curve (SROC) of ARFI elastography in detecting significant fibrosis (defined as 4>F?2) in NAFLD patients. Study quality was assessed using the Quality Assessment of Studies of Diagnostic Accuracy included in Systematic Review (QUADAS-2). Results The summary sensitivity and specificity of ARFI in detecting significant fibrosis were 80.2% (95% confidence interval (CI): 0.758–0.842; p = 0.0000) and 85.2% (95% CI: 0.808–0.890), p = 0.1617), respectively. The pooled diagnostic odds ratio of ARFI in detecting significant fibrosis was 30.13 (95% CI: 12.08–75; chi-squared = 14.59, p = 0.0237). The area under the SROC curve (AUC) was 0.898 (standard error (SE): 0.031) with a Q* index of 0.830 (SE: 0.033). Conclusions ARFI elastography appears to be modestly accurate in detecting significant fibrosis in NAFLD patients. Future studies in this field should provide head-to-head comparisons of ARFI elastography versus other elastographic imaging modalities in NAFLD patients. PMID:26131717

  19. Portal Vein Embolization with Radiolabeled Polyvinyl Alcohol Particles in a Swine Model: Hepatic Distribution and Implications for Pancreatic Islet Cell Transplantation

    SciTech Connect

    Owen, Richard J., E-mail: drrichardowen@tbwifi.c [University of Alberta, Department of Radiology and Diagnostic Imaging, Faculty of Medicine, Walter Mackenzie Health Sciences Center (Canada); Mercer, John R. [University of Alberta, Department of Oncologic Imaging, Faculty of Medicine (Canada); Al-Saif, Faisal; Molinari, Michele [University of Alberta Hospital, Department of Surgery (Canada); Ashforth, Robert A. [University of Alberta, Department of Radiology and Diagnostic Imaging, Faculty of Medicine, Walter Mackenzie Health Sciences Center (Canada); Rajotte, Ray V. [University of Alberta, Surgical-Medical Research Institute (Canada); Conner-Spady, Barbara [University of Alberta, Department of Radiology and Diagnostic Imaging, Faculty of Medicine, Walter Mackenzie Health Sciences Center (Canada); Shapiro, A. M. James [University of Alberta, Clinical Islet Transplant Program (Canada)

    2009-05-15

    The distribution of radiolabeled polyvinyl alcohol microspheres (PVAMs) when infused into the portal vein of domestic swine was investigated, with the purpose of assessing implications for pancreatic islet cell transplantation. PVAMs measuring 100-300 {mu}m (Contour SE) and labeled with {sup 99m}Tc were infused into the main portal vein of 12 swine, with intermittent portal venous pressure measurements. The infusion catheter was introduced antegradely via direct or indirect cannulation of the portal vein. The liver was subsequently divided into anatomical segments. Radioactivity (decay corrected) was measured for {sup 99m}Tc microsphere synthesis, dose preparation, gross organ activities, tissue samples, and blood. Particulate labeling, catheter positioning, and infusion were successful in all cases. The number of particles used was (185,000 {+-} 24,000) with a volume of 1 ml. Mean portal pressure at 5 min was significantly higher than baseline, but without a significant difference at 15 min. Extrahepatic tissue and serum radioactivity was negligible. A significant difference in number of radioactive particles per gram was detected between segments 6/7 and segments 5/8. Intrasegmental activity was analyzed, and for segments 2/3 a significant difference in the percentage dose per gram across samples was demonstrated (P = 0.001). Effective and stable radiolabeling of PVAMs with {sup 99m}Tc-sulfur colloid was demonstrated. Portal venous infusion of 100- to 300-{mu}m particles showed entrapment in the sinusoidal hepatic system with transient portal pressure elevation. Preferential embolization into the right lateral and posterior segments occurs, suggesting that flow dynamics/catheter tip position plays a role in particle distribution.

  20. 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 ...

  1. Role of Hypoxia Inducing Factor-1? in Alcohol-Induced Autophagy, Steatosis and Liver Injury in Mice

    PubMed Central

    Ni, Hong-Min; Bhakta, Amar; Wang, Shaogui; Li, Zhenrui; Manley, Sharon; Huang, Heqing; Copple, Bryan; Ding, Wen-Xing

    2014-01-01

    Chronic alcohol causes liver hypoxia and steatosis, which eventually develops into alcoholic liver disease (ALD). While it has been known that alcohol consumption activates hepatic hypoxia inducing factor-1? (HIF-1?), conflicting results regarding the role of HIF-1? in alcohol-induced liver injury and steatosis in mice have been reported. In the present study, we aimed to use hepatocyte-specific HIF-1? knockout mice to eliminate the possible compensatory effects of the single knockout of the 1? subunit of HIF to study the role of HIFs in ALD. C57BL/6 wild type mice were treated with acute ethanol to mimic human binge drinking. Matched wild-type and hepatocyte specific HIF-1? knockout mice were also subjected to a recently established Gao-binge alcohol model to mimic chronic plus binge conditions, which is quite common in human alcoholics. We found that acute alcohol treatment increased BNIP3 and BNIP3L/NIX expression in primary cultured hepatocytes and in mouse livers, suggesting that HIF may be activated in these models. We further found that hepatocyte-specific HIF-1? knockout mice developed less steatosis and liver injury following the Gao-binge model or acute ethanol treatment compared with their matched wild type mice. Mechanistically, protection against Gao-binge treatment-induced steatosis and liver injury was likely associated with increased FoxO3a activation and subsequent induction of autophagy in hepatocyte-specific HIF-1? knockout mice. PMID:25536043

  2. Accumulation of xenotransplanted canine bone marrow cells in NOD/SCID/?c(null) mice with acute hepatitis induced by CCl4.

    PubMed

    Kato, Takashi; Hisasue, Masaharu; Segawa, Kazuhito; Fujimoto, Ayumi; Makiishi, Eri; Neo, Sakurako; Yasuno, Kyohei; Kobayashi, Ryosuke; Tsuchiya, Ryo

    2013-07-31

    Bone marrow cell infusion (BMI) has recently been suggested as an effective therapy for refractory liver disease; however, the efficiency of BMI using canine bone marrow cells (cBMCs) has not been reported. We evaluated the accumulation potential of cBMCs in a mouse model of acute liver failure. Acute hepatitis was induced by carbon tetrachloride (CCl4) treatment in NOD/SCID/?c(null)(NOG) mice and wild-type (WT) C57BL mice, and the characteristics of liver dysfunction and the degree of hepatic injury and regeneration were compared between the two mouse models. Next, female CCl4-treated NOG mice were xenotransplanted with male PKH26-labeled cBMCs, and the potential of cBMCs to accumulate in injured liver tissue compartments was examined. Fluorescence microscopy was performed to histologically detect the infused cBMCs, and DNA polymerase chain reaction was performed for detection of the male Y chromosome (SRY gene) in the recipient female NOG mice. The number of PKH26-positive cBMCs transplanted in the liver tissue gradually increased in the NOG mice. The infused cBMCs were located in the necrotic area of the liver at an early stage after transplantation, and most had accumulated a week after transplantation. However, the therapeutic efficacy of the xenotransplantation remained unclear, because no significant differences were observed concerning the extent liver injury and regeneration between the cBMC-transplanted and saline control mice. These results suggest that cBMCs will specifically accumulate in injured liver tissue and that BMC transplantation may have the potential to repair liver deficiency. PMID:23411484

  3. Studies on hepatoprotective and antioxidant actions of Strychnos potatorum Linn. seeds on CCl4-induced acute hepatic injury in experimental rats.

    PubMed

    Sanmugapriya, E; Venkataraman, S

    2006-04-21

    Strychnos potatorum Linn. seeds are used in the Indian traditional system of medicine for the treatment of hepatopathy, nephropathy, gonorrhoea, leucorrhoea, gastropathy, bronchitis, chronic diarrhoea, strangury, renal and vesicle calculi, diabetes and eye diseases. The present study describes the hepatoprotective and antioxidant activities of the seed powder (SPP) and aqueous extract (SPE) of Strychnos potatorum seeds against CCl4-induced acute hepatic injury. Hepatic injury was achieved by injecting 3 ml/kg, s.c. of CCl4 in equal proportion with olive oil. Both SPP and SPE at the doses 100 and 200 mg/kg, p.o. offered significant (p < 0.001) hepatoprotective action by reducing the serum marker enzymes like serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT). They also reduced the elevated levels of ALP and serum bilirubin. Reduced enzymic and nonenzymic antioxidant levels and elevated lipid peroxide levels were restored to normal by administration of SPP and SPE. Histopathological studies further confirmed the hepatoprotective activity of SPP and SPE when compared with the CCl4 treated control groups. The results obtained were compared with Silymarin (50 mg/kg, p.o.), the standard drug. In conclusion, SPE (200 mg/kg, p.o.) showed significant hepatoprotective activity similar to that of the standard drug, Silymarin (50 mg/kg, p.o.). PMID:16388923

  4. Alcohol Facts and Statistics

    MedlinePLUS

    ... to a range of acute consequences, including injuries, sexual assaults, and even deaths—including those from car crashes. ... of 18 and 24 report experiencing alcohol-related sexual assault or date rape. 24 Roughly 20 percent of ...

  5. Acute hepatic failure and multi-system organ failure secondary to replacement of the liver with metastatic melanoma

    PubMed Central

    Kaplan, Gilaad G; Medlicott, Shaun; Culleton, Bruce; Laupland, Kevin B

    2005-01-01

    Background Metastatic malignant melanoma to the liver resulting in fulminant hepatic failure is a rare occurrence. Case presentation A 46 year old man presented to hospital with massive hepatomegaly, elevated liver enzymes and increased lactate three weeks following resection of a malignant melanoma from his shoulder (Clark level 5). Initially stable, he decompensated 24 to 48 hours subsequent to presentation with respiratory failure requiring mechanical ventilation, distributive shock requiring high dose vasopressor infusion, coagulopathy refractory to plasma infusion, progressive rise in liver enzymes and severe metabolic abnormalities including hyperkalemia, acidosis, hyperphosphatemia, hyperuricemia and hypocalcemia. Refractory to aggressive physiologic support he received palliation. Autopsy revealed >80% liver infiltration by metastatic malignant melanoma. Conclusion We report a case of fulminant hepatic failure secondary to metastatic malignant melanoma infiltration of the liver. PMID:15989692

  6. Molecular characterization of hepatitis A virus isolated from acute gastroenteritis patients in the Seoul region of Korea

    Microsoft Academic Search

    S.-H. Park; E.-J. Kim; J.-H. Lee; S.-S. Choi; M.-S. Kim; S.-S. Jung; G.-Y. Han; H.-S. Yun; D.-S. Chun; S.-S. Oh; H.-S. Kim

    2009-01-01

    Hepatitis A virus (HAV) is a major public health problem throughout the world. As a result of declining HAV endemic in Korea,\\u000a an increasing number of children and adolescents have become susceptible to HAV infection. HAV is related with sanitation\\u000a conditions of the environment and is transmitted via the fecal–oral route, either through person-to-person contact or by contaminated\\u000a water and

  7. Immunological studies in patients with chronic active hepatitis. Cytotoxic activity of lymphocytes to autochthonous liver cells grown in tissue culture.

    PubMed Central

    Paronetto, F; Vernace, S

    1975-01-01

    The cytotoxic activity of lymphocytes against autochthonous liver cells was studied in patients with chronic liver diseases and in controls. Cytotoxicity of lymphocytes was observed in eight of ten patients with chronic active hepatitis, two patients with chronic persistent hepatitis, one patient with primary biliary cirrhosis, one patient with alcoholic hepatitis and carcinoma of the pancreas, and in three of five patients with acute viral hepatitis, but not in seven patients without liver alteration or with miscellaneous liver diseases. Serum was not cytotoxic, but in three patients it decreased the cytotoxicity of lymphocytes. Cytotoxicity was seen in both HBAg-positive and HBAg-negative patients, appears to be influenced by therapy, and does not correlate with autoantibodies. These data support the hypothesis of an aggressive activity of lymphocytes in certain liver diseases. PMID:1204242

  8. Effect of Non-Alcoholic Compounds of Alcoholic Drinks on the Pancreas

    Microsoft Academic Search

    Peter Feick; Andreas Gerloff; Manfred V. Singer

    2007-01-01

    Over the past 30 years the role of alcohol (ethanol) in the development of acute and chronic pancreatitis has been intensively investigated. However, ethanol is generally consumed in form of alcoholic beverages which contain numerous non-alcoholic compounds. At least on gastric acid secretion it has been convincingly demonstrated that alcohol and alcoholic beverages have markedly different effects. In the present

  9. Categories of Alcohol Consumers: Definitions and Criteria of Alcohol Addiction

    Microsoft Academic Search

    Claude Tomberg

    2010-01-01

    Common patterns of alcohol consumption are described with their main criteria, blood alcohol levels, and diagnostic criteria. Binge drinking, an acute alcohol intoxication pattern of particularly concern, is also described, as it appears to be the most common pattern among teenagers when the brain is not yet mature. A number of classification schemes have been proposed specially for social drinking

  10. Alcohol, host defence and society

    Microsoft Academic Search

    Steve Nelson; Jay K. Kolls

    2002-01-01

    Impaired health caused by alcohol abuse has been known throughout recorded history. Over the past century, alcohol abuse has been clearly linked to host susceptibility to infectious disease, particularly bacterial pneumonia. Recently, both acute and chronic alcohol intake have been shown to result in specific defects in innate and adaptive immunity; these could, in principle, be subjected to specific modulation

  11. Regulation of the neutralizing anti-hepatitis B surface (HBs) antibody response in vitro in HBs vaccine recipients and patients with acute or chronic hepatitis B virus (HBV) infection†

    PubMed Central

    BÖCHER, W O; HERZOG-HAUFF, S; HERR, W; HEERMANN, K; GERKEN, G; MEYER ZUM BÜSCHENFELDE, K-H; LÖHR, H F

    1996-01-01

    Antibodies directed to the HBs antigen indicate viral clearance and the development of life-long immunity in patients that recovered from HBV infection. In HBs antigen vaccine recipients anti-HBs antibodies provide protective immunity. However, little is known about the regulation of this HBs-specific antibody response. The existence of anti-HBs-secreting B cells was demonstrated using the highly sensitive ELISPOT technique compared with conventional ELISA in serum and cell culture supernatants. In the peripheral blood of patients with acute self-limited hepatitis B, HBs-specific B cells were demonstrated with a high frequency despite undetectable anti-HBs serum antibodies. HBV-immunized patients that had recovered from infection and vaccine recipients had significantly lower frequencies, whereas chronic HBV carriers and negative controls showed no anti-HBs-secreting B cells. Coculture experiments of isolated B and T cells revealed that the anti-HBs antibody response was restricted to the presence of T helper cells, but not to identical HLA class II molecules. Allogeneic T cells derived from vaccine recipients or chronic HBV carriers stimulated the HBs-specific B cell response in HBs vaccine recipients. Otherwise, isolated T helper cells could never provide sufficient help to induce the HBs-specific B cell response in chronic HBV carriers. Furthermore, peripheral blood mononuclear cells (PBMC) of six out of 10 vaccine recipients, one out of five HBV-immunized patients, but of no chronic HBV carrier showed a proliferative response to different HBs antigen preparations. This study demonstrated a high frequency of circulating anti-HBs-producing B cells in the early phase of acute HBV infection, but a lower frequency of HBs-specific B cells years after resolution of HBV infection. In chronic HBV carriers, however, deficient HBs-specific T and B cell responses were observed. PMID:8697635

  12. Moderate acute alcohol intoxication has minimal effect on surround suppression measured with a motion direction discrimination task.

    PubMed

    Read, Jenny C A; Georgiou, Renos; Brash, Claire; Yazdani, Partow; Whittaker, Roger; Trevelyan, Andrew J; Serrano-Pedraza, Ignacio

    2015-01-01

    A well-studied paradox of motion perception is that, in order to correctly judge direction in high-contrast stimuli, subjects need to observe motion for longer in large stimuli than in small stimuli. This effect is one of several perceptual effects known generally as "surround suppression." It is usually attributed to center-surround antagonism between neurons in visual cortex, believed to be mediated by GABA-ergic inhibition. Accordingly, several studies have reported that this index of surround suppression is reduced in groups known to have reduced GABA-ergic inhibition, including older people and people with schizophrenia and major depressive disorder. In this study, we examined the effect on this index of moderate amounts of ethanol alcohol. Among its many effects on the nervous system, alcohol potentiates GABA-ergic transmission. We therefore hypothesized that it should further impair the perception of motion in large stimuli, resulting in a stronger surround-suppression index. This prediction was not borne out. Alcohol consumption slightly worsened duration thresholds for both large and small stimuli, but their ratio did not change significantly. PMID:25583875

  13. Alcohol, vitamin A, and cancer

    Microsoft Academic Search

    Xiang-Dong Wang

    2005-01-01

    Chronic and excessive alcohol intake is associated with an increased risk of a variety of cancers (e.g., oral cavity, larynx, esophagus, liver, lung, colorectal, and breast). Retinoids (vitamin A and its derivatives) are known to exert profound effects on cellular growth, cellular differentiation, and apoptosis, thereby controlling carcinogenesis. Lower hepatic vitamin A levels have been well documented in alcoholics. Substantial

  14. [Alcohol induced cognitive deficits].

    PubMed

    Weiss, Elisabeth; Singewald, Evelin M; Ruepp, Beatrix; Marksteiner, Josef

    2014-01-01

    Previous studies could show a complex relationship between alcohol consumption and cognition but also with processes of ageing both social and biological. Acute effects of alcohol during intoxication include clinical signs such as excitation and reduced inhibition, slurred speech, and increased reaction time but also cognitive dysfunction, especially deficits in memory functions. However, these cognitive deficits during alcohol intoxication are reversible while patients with alcohol addiction and chronic alcohol intake show severe impairments of cognitive functions especially deficits in executive functions. Frontal executive impairments in these patients include deficits in problem solving, abstraction, planning, organizing, and working memory.Additionally, gender specific deficits are relevant for the course of the disease and its concomitant health problems with female alcoholics showing a higher vulnerability for cognitive dysfunction and brain atrophy at earlier stages of alcoholism history. PMID:23868552

  15. The Expression of PD-1 Ligands and Their Involvement in Regulation of T Cell Functions in Acute and Chronic Woodchuck Hepatitis Virus Infection

    PubMed Central

    Zhang, Ejuan; Zhang, Xiaoyong; Liu, Jia; Wang, Baoju; Tian, Yongjun; Kosinska, Anna D.; Ma, Zhiyong; Xu, Yang; Dittmer, Ulf; Roggendorf, Michael; Yang, Dongliang; Lu, Mengji

    2011-01-01

    Background The programmed cell death 1 (PD-1)/programmed death-1 ligand 1 (PD-L1) system may play a role in the negative regulation of T cell functions in hepatitis B virus (HBV) infection. Thus, it is important to study its role in the widely used animal model for HBV infection of woodchucks with woodchuck hepatitis virus (WHV). Methods Woodchuck PD-L1 (wPD-L1) and -L2 (wPD-L2) were cloned and characterized. The levels of wPD-L1 expression in primary woodchuck hepatocytes (PWH), peripheral blood mononuclear cells (PBMCs), and liver tissue of naive and WHV-infected woodchucks were examined by real time reverse transcription (RT)-PCR and flow cytometry. Using antibodies against wPD-L1 and -L2, the effect of blocking PD-1/PD-L1/PD-L2 interaction on the proliferation and degranulation of woodchuck PBMCs was examined. Principal Findings Both wPD-L1 and -L2 showed a high homology to their counterparts of other mammalian species and humans. WPD-L1 expression in PWH and PBMCs of naive animals was low but could be stimulated by Toll-like receptor (TLR) ligands and interferons (IFN). WPD-L1 expression in liver tissue was significantly higher than that measured in PWHs and was slightly elevated during acute and chronic WHV infection. However, wPD-1 and wPD-L1 expression on PBMCs was strongly up-regulated during acute and chronic infection. In vitro blockade with antibodies against wPD-L1 and -L2 partially enhanced proliferation and degranulation of PBMCs from WHV-infected woodchucks. Conclusions Our results demonstrated that wPD-1/wPD-L1 expression in hepatocytes and PBMCs can be induced by different inflammatory stimuli and is up-regulated mainly on PBMCs during WHV infection. A blockade of the woodchuck PD-1/PD-L pathway could partially enhance T cell functions in WHV infection. PMID:22022563

  16. Analysis of Hepatitis B Virus Intrahepatic Covalently Closed Circular DNA and Serum Viral Markers in Treatment-Naive Patients with Acute and Chronic HBV Infection

    PubMed Central

    Zou, Zhengsheng; Liu, Yan; Li, Baosen; Sun, Ying; Li, Xiaodong; Liu, Shuhong; Cai, Shaoping; Yao, Weimin; Xin, Shaojie; Lu, Fengmin; Xu, Dongping

    2014-01-01

    Background This study aimed to investigate the relationships of intrahepatic cccDNA with serum HBsAg and with HBV DNA in treatment-naive patients throughout acute and chronic HBV infection. Methods A total of 120 patients who had a liver biopsy were enrolled, including 19 with acute hepatitis B (AHB), and 101 patients with chronic HBV infection (CHB) of whom were 10 in immune-tolerant (IT) phase, 59 in immune-clearance (IC) phase, 8 in low-replicative (LR) phase, and 24 in HBeAg-negative hepatitis (ENH) phase. Intrahepatic cccDNA, serum HBsAg and serum HBV DNA levels were comparatively analyzed. Results The median intrahepatic cccDNA levels were 0.18 4.80, 3.81, 0.22 and 0.97 copies/cell for patients with AHB, CHB-IT, CHB-IC, CHB-LR, and CHB-ENH, respectively. In AHB patients, intrahepatic cccDNA was positively correlated with serum HBsAg (r?=?0.665, P?=?0.003), as well as serum HBV DNA (r?=?0.536, P?=?0.022). In CHB patients, intrahepatic cccDNA was positively correlated with serum HBsAg in the IC phase (r?=?0.392, P?=?0.005), and with serum HBV DNA in the IC phase (r?=?0.301, P?=?0.036) and ENH phase (r?=?0.588, P?=?0.013). HBV replicative efficiency, defined as the ratio of serum HBV DNA to intrahepatic cccDNA, was obviously lower in AHB and CHB-LR patients than in CHB-IT, CHB-IC and CHB-ENH patients (0.70 and 0.53 vs. 1.12, 1.09 and 0.99, P<0.001, values were logarithmic transformed for analysis). In CHB-IC patients, HBV replicative efficiency was positively correlated with histological activity index of liver inflammation (r?=?0.308, P?=?0.009). Conclusion Serum HBsAg and HBV DNA levels may reflect the amount of active intrahepatic cccDNA in treatment-naive AHB and CHB-IC patients. Reduced intrahepatic cccDNA and HBV replicative efficiency may imply effective immune control of HBV infection. PMID:24551214

  17. Hepatic cytochrome P450 3A drug metabolism is reduced in cancer patients who have an acute-phase response

    Microsoft Academic Search

    L P Rivory; K A Slaviero; S J Clarke

    2002-01-01

    Inflammatory disease states (infection, arthritis) are associated with reduced drug oxidation by the cytochrome P450 3A system. Many chemotherapy agents are metabolised through this pathway, and disease may therefore influence inter-individual differences in drug pharmacokinetics. The purpose of this study was to assess cytochrome P450 3A function in patients with advanced cancer, and its relation to the acute-phase response. We

  18. 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

  19. Hepatic Steatosis In Patients Undergoing Bariatric Surgery and its Relationship to Body Mass Index and Co-Morbidities

    Microsoft Academic Search

    Myriam Moretto; Carlos Kupski; Cláudio Corá Mottin; Giuseppe Repetto; Marcelo Garcia Toneto; Jacqueline Rizzolli; Diovanne Berleze; Cesar Luis de Souza Brito; Daniela Casagrande; Fernanda Colossi

    2003-01-01

    Background: Although non-alcoholic hepatitis usually is asymptomatic and benign, this condition may progress to cirrhosis\\u000a and hepatic failure. Some findings are similar to alcoholic hepatitis, but there is no history of excessive alcohol consumption.\\u000a Among the factors associated with non-alcoholic hepatitis, obesity, diabetes and dyslipidemia are the most important. Methods:\\u000a 77 consecutive patients undergoing bariatric surgery had their liver biopsy

  20. 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 ...

  1. Alcoholism - resources

    MedlinePLUS

    Resources - alcoholism ... The following organizations are good resources for information on alcoholism : Alcoholics Anonymous - www.alcoholics-anonymous.org Al-Anon/Alateen - www.al-anon.org National Institute on Alcohol ...

  2. Alcohol Alert

    MedlinePLUS

    You are here Home » Alcohol Alert Alcohol Alert The NIAAA Alcohol Alert is a quarterly bulletin that disseminates important research findings on a single aspect of alcohol abuse and alcoholism. Please ...

  3. Long-term follow-up of acute and chronic nonA, non-B post-transfusion hepatitis: evidence of progression to liver cirrhosis

    Microsoft Academic Search

    G Realdi; A Alberti; M Rugge; A M Rigoli; F Tremolada; L Schivazappa; A Ruol

    1982-01-01

    The long-term outcome of non-A, non-B post-transfusion hepatitis was evaluated in 21 patients who developed the illness after open-heart surgery and could be followed thereafter up to five years. Histological chronic sequelae were documented in 13 patients, and consisted of chronic persistent hepatitis in one case, chronic lobular hepatitis in two and chronic active hepatitis in 10, five of whom

  4. Increased Toll-Like Receptor 4 in Cerebral Endothelial Cells Contributes to the Astrocyte Swelling and Brain Edema in Acute Hepatic Encephalopathy

    PubMed Central

    Jayakumar, A.R.; Tong, X.Y.; Curtis, K.M.; Ruiz-Cordero, R.; Abreu, M.T.; Norenberg, M.D.

    2013-01-01

    Astrocyte swelling and the subsequent increase in intracranial pressure and brain herniation are major clinical consequences in patients with acute hepatic encephalopathy (AHE). We recently reported that conditioned media (CM) from brain endothelial cells (ECs) exposed to ammonia, a mixture of cytokines (CKs) or lipopolysaccharide (LPS), when added to astrocytes caused cell swelling. In the present study we investigated the possibility that ammonia and inflammatory agents activate the toll-like receptor 4 (TLR4) in ECs, resulting in the release of factors that ultimately cause astrocyte swelling. We found a significant increase in TLR4 protein expression when ECs were exposed to ammonia, CKs or LPS alone, while exposure of ECs to a combination of these agents potentiated such effects. Additionally, astrocytes exposed to CM from TLR4-silenced ECs that were treated with ammonia, CKs or LPS, resulted in a significant reduction in astrocyte swelling. TLR4 protein upregulation was also detected in rat brain ECs after treatment with the liver toxin thioacetamide (TAA), and that TAA-treated TLR4 knock-out mice exhibited a reduction in brain edema. These studies strongly suggest that ECs significantly contribute to the astrocyte swelling/brain edema in AHE, likely as a consequence of increased TLR4 protein expression by blood-borne noxious agents. PMID:24261962

  5. ASS and SULT2A1 are Novel and Sensitive Biomarkers of Acute Hepatic Injury-A Comparative Study in Animal Models

    PubMed Central

    Prima, Victor; Cao, Mengde; Svetlov, Stanislav I

    2013-01-01

    Liver and kidney damage associated with polytrauma, endotoxic shock/sepsis, and organ transplantation, are among the leading causes of the multiple organ failure. Development of novel sensitive biomarkers that detect early stages of liver and kidney injury is vital for the effective diagnostics and treatment of these life-threatening conditions. Previously, we identified several hepatic proteins, including Argininosuccinate Synthase (ASS) and sulfotransferases which were degraded in the liver and rapidly released into circulation during Ischemia/Reperfusion (I/R) injury. Here we compared sensitivity and specificity of the newly developed sandwich ELISA assays for ASS and the sulfotransferase isoform SULT2A1 with the standard clinical liver and kidney tests Alanine Aminotransferase (ALT) and Aspartate Transaminase (AST) in various pre-clinical models of acute injury. Our data suggest that ASS and SULT2A1 have superior characteristics for liver and kidney health assessment in endotoxemia, Ischemia/Reperfusion (I/R), chemical and drug-induced liver injury and may be of high potential value for clinical applications. PMID:23724364

  6. ForPeerReview SEROCONVERSION TO HEPATITIS C VIRUS ALTERNATE

    E-print Network

    Paris-Sud XI, Université de

    ForPeerReview SEROCONVERSION TO HEPATITIS C VIRUS ALTERNATE READING FRAME PROTEIN DURING THE ACUTE de Bacteriologie and Virologie Keywords: ARFP, antibodies, acute hepatitis C, seroconversion (Baltimore, Md.) 2009;49(5):1449-59" DOI : 10.1002/hep.22821 #12;ForPeerReview SEROCONVERSION TO HEPATITIS C

  7. 69 FR 58371 - Microbiology Devices; Reclassification of Hepatitis A Virus (HAV) Serological Assays (IgM...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2004-09-30

    ...Microbiology Devices; Reclassification of Hepatitis A Virus (HAV) Serological Assays...Administration (FDA) is proposing to reclassify hepatitis A virus (HAV) serological assays from...signs and symptoms consistent with acute hepatitis A or for determining if an...

  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. Quinine allergy causing acute severe systemic illness: report of 4 patients manifesting multiple hematologic, renal, and hepatic abnormalities

    PubMed Central

    2003-01-01

    Quinine is widely used for the common symptom of leg cramps. Quinine tablets require a prescription, but quinine and the product from which it is derived, cinchona, are also available without prescription. They are components of over-the-counter remedies for many common symptoms, of nutrition products, and of beverages such as tonic water and bitter lemon. Although quinine has been used for centuries, initially as an extract from the bark of the cinchona tree, allergic reactions to quinine can be severe and can affect multiple organs. These allergic reactions can cause thrombocytopenia, neutropenia, anemia, disseminated intravascular coagulation, acute renal failure, liver toxicity, and neurological abnormalities. Because quinine use is often intermittent, defining quinine as a cause of an acute disorder may be difficult. Moreover, since quinine use is often self-regulated, patients may not mention it in response to direct questions about medication use, adding to diagnostic difficulty. The diversity and severity of quinine-associated disorders and the difficulties of diagnosis are illustrated by the presentation of 4 case histories. Awareness of the variety of potential quinine-associated reactions is important for accurate diagnosis and critical for prevention of recurrent illness. PMID:16278718

  10. 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

  11. 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

  12. Alcoholism, Alcohol, and Drugs

    ERIC Educational Resources Information Center

    Rubin, Emanuel; Lieber, Charles S.

    1971-01-01

    Describes research on synergistic effects of alcohol and other drugs, particularly barbiturates. Proposes biochemical mechanisms to explain alcoholics' tolerance of other drugs when sober, and increased sensitivity when drunk. (AL)

  13. [Biliocalculous disease as a cause of local hepatitis].

    PubMed

    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:25507012

  14. Spin-trapping studies of hepatic free radicals formed following the acute administration of ethanol to rats: In vivo detection of 1-hydroxyethyl radicals with PBN

    SciTech Connect

    Reinke, L.A.; Kotake, Y.; McCay, P.B.; Janzen, E.G. (Department of Pharmacology, University of Oklahoma Health Sciences Center, Oklahoma City (United States))

    1991-01-01

    The generation of free radicals in rat liver following the acute oral administration of ethanol was studied with the spin-trapping method, using a deuterated derivative of phenyl-N-tert-butylnitrone (PBN-d14) as the spin-trapping agent. After administration of ethanol and PBN-d14 to rats, organic extracts of the liver were prepared and subjected to ESR spectroscopy. In the case of ethanol-treated rats, the ESR spectra indicated that mixtures of radicals had been trapped, while spectra from control rats were essentially negative. The predominant spin adduct detected after ethanol treatment is proposed to be from a carbon-centered, primary alkyl radical, based on gamma-hydrogen hyperfine splitting patterns observed with PBN-d14. Oxygen-centered radicals also contributed to the ESR spectra. Liver extracts also contained low concentrations of the 1-hydroxyethyl radical spin adduct, which was indicated by weak spectral lines corresponding to those of the 1-13C-ethanol adduct. These data confirm previous suggestions that ethanol is metabolized to a free radical metabolite in rat liver. In addition, some information on types of lipid radicals generated during alcohol intoxication has been obtained.

  15. Similar effects of intranasal oxytocin administration and acute alcohol consumption on socio-cognitions, emotions and behaviour: Implications for the mechanisms of action.

    PubMed

    Mitchell, Ian J; Gillespie, Steven M; Abu-Akel, Ahmad

    2015-08-01

    Oxytocin (OT) plays a critical role in the formation of long lasting social attachments across a range of mammalian species. Raising intracerebral OT levels by intranasal administration of the neuropeptide (inOT) can also have pronounced effects on human sociocognitive functioning. inOT has been associated with increasing altruism, generosity, empathy and trust while decreasing fear, anxiety and stress reactions via neural mechanisms which are yet to be fully elucidated. The observation of the prosocial effects of OT has led to speculation about the role the peptide might play in some psychiatric conditions and debate as to its potential therapeutic uses. Here we note the great similarity in the sociocognitive effects that can be induced by inOT and the effects of acute consumption of modest does of alcohol. We further reflect on how both compounds may act on limbic and prefrontal cortical structures to increase GABAergic transmission, thereby facilitating the release of prepotent responses, that is, more automatic responses which are associated with earlier developmental stages. PMID:25956250

  16. Effects of nonylphenol on hepatic testosterone metabolism and the expression of acute phase proteins in winter flounder (Pleuronectes americanus): comparison to the effects of Saint John's Wort.

    PubMed

    Baldwin, William S; Roling, Jonathan A; Peterson, Sean; Chapman, Laura M

    2005-01-01

    4-Nonylphenol (4-NP), a major by-product of alkylphenol ethoxylates, is used in several industries and as a consequence is quite common in rivers, estuaries and other aquatic environments that receive sewage discharges or are near offshore oil platforms. 4-NP is an environmental estrogen that also binds human and rodent Pregnane X-receptor (PXR), the orphan nuclear receptor that controls the expression of several detoxication genes in mammals, including several CYP3A and CYP2B family members. These P450s preferentially hydroxylate testosterone in the 6beta- and 16beta-positions, respectively. In this study, the effects of 4-NP on testosterone metabolism and hepatic CYP3A induction were compared to the effects of St. John's Wort (SJW), a well established mammalian PXR agonist, in winter flounder. Male winter flounder (Pleuronectes americanus) were injected with 100 mg/kg/day 4-NP or 500 mg/kg/day SJW or both (S and N) every 24 h. Forty-eight hours after the initial injections, flounder were euthanized. Western blots and testosterone 6beta-hydroxylation indicated that CYP3A was increased 50% by 4-NP, but was not affected by SJW. Testosterone 16beta-hydroxylase activity was also significantly increased in flounder treated with 4-NP (2.8 x), but not with SJW. This is not consistent with our hypothesis that both SJW and 4-NP would induce CYP3A. Subtractive hybridization was performed between control and 4-NP treated hepatic mRNA samples to isolate differentially expressed genes. Subtractive hybridization indicated that several acute phase proteins were altered by 4-NP. Quantitative real-time PCR (Q-PCR) confirmed 4-NP altered the expression of complement components C8b, cathepsin L, C-type lectin domain, FK506 binding protein 2 precursor (FKBP2) and an EST (expressed sequence tag). SJW and 4-NP treated flounder demonstrated similar induction profiles for the EST, cathepsin L and FKBP2, suggesting that SJW was at a sufficient dose to alter gene expression but not induce P450s. In conclusion, testosterone hydroxylase activity and Western blots indicate that SJW did not activate detoxication pathways in a similar manner to 4-NP. PMID:15792627

  17. Reduction of metabolic signs of acute stress in male mice by Papaver rhoaes hydro-alcoholic extract.

    PubMed

    Ranjbaran, M; Mirzaei, P; Lotfi, F; Behzadi, S; Sahraei, H

    2013-10-01

    In the present study, effects of hydro-alcoholic extract of Papaver rhoeas L. (Papaveraceae) on the metabolic changes induced by electro foot shock stress in male NMRI mice (25-30 g) has been investigated. The mice were received electric foot shock (40 mV) for 100 sec. Plasma corticosterone levels, food and water intake and delay to eating (Anorexia) were assessed 20 min later. Different doses of the plant extract (15, 30 and 60 mg kg(-1)), or saline (10 mL kg(-1)) was injected to the animals intraperitoneally 30 min before the stress. The control groups received saline (10 mL kg(-1)) or the extract (15, 30 and 60 mg kg(-1)) and 30 min later were exposed to the apparatus but did not received stress. Our results indicated that stress can increase plasma corticosterone level significantly and the extract can exacerbate the stress effect. However, stress could reduce food and water intake and increase delay to eating times which were inhibited by the extract pretreatment. The results indicate that administration of the extract of Papaver rhoeas can reduce the side effects of stress but increases plasma corticosterone level which may be due to its effects on the adrenal gland. PMID:24502164

  18. 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

  19. Hepatitis B Virus Genotype Distribution and Genotype-Specific BCP/preCore Substitutions in Acute and Chronic Infections in Argentina

    PubMed Central

    González López Ledesma, María Mora; Mojsiejczuk, Laura Noelia; Rodrigo, Belén; Sevic, Ina; Mammana, Lilia; Galdame, Omar; Gadano, Adrian; Fainboim, Hugo; Campos, Rodolfo; Flichman, Diego

    2015-01-01

    Aim In order to assess Hepatitis B Virus genotype (g) and subgenotype (sg) implications in the course of infection, 234 HBsAg positive patients in different infection stages were characterized (66 acute infections, 63 HBeAg positive chronic infections and 105 anti-HBe positive chronic infections). Results Overall, sgA2 (17.9%), gD (20.9%), sgF1b (34.2%) and sgF4 (19.7%) were the most prevalent. Subgenotype F1b was overrepresented in acute and chronic HBeAg infections (56.1%), whereas gD was the most frequent (40.0%) in anti-HBe positive chronic infections. Among chronic infections, HBeAg positivity rates were 50.0, 12.5, 62.8 and 35.3% for sgA2, gD, sgF1b and sgF4, respectively (p <0.05). A bias toward BCP/preCore mutations was observed among genotypes. In anti-HBe positive chronic infections, sgF1b was more prone to have A1762T/G1764A mutation than sgA2, sgF4 and gD (75.0, 40.0, 33.3 and 31.8%, p<0.005), whereas in the pC region, gD and sgF4 were more likely to have G1896A than sgA2 and sgF1b (81.0, 72.7, 0.0 and 31.3%, p <0.001). The unexpected low frequency of the G1896A mutation in the sgF1b (despite carrying 1858T) prompted us to perform a further analysis in order to identify genotype-specific features that could justify the pattern mutations observed. A region encompassing nucleotides 1720 to 1920 showed the higher dissimilarity between sgF1b and sgF4. Genotypes and subgenotypes carrying the 1727G, 1740C and 1773T polymorphisms were prevented to mutate position 1896. Discussion HBeAg seroconversion is a critical event in the natural history of HBV infection. Differences in the HBeAg positivity rate might be relevant since different studies have observed that delayed HBeAg seroconversion is associated with a more severe clinical course of infection, highlighting the critical role that genotypes/subgenotypes might play in the progression of HBV infection. Polymorphisms in the regions 1720 to 1920 could be involved in the molecular mechanisms underlying seroconversion of each genotype/subgenotype. PMID:25822666

  20. Calcium-Channel-Blocking Agent in the Treatment of Acute Alcohol Withdrawal – Caroverine versus Meprobamate in a Randomized Double-Blind Study

    Microsoft Academic Search

    S. Koppi; G. Eberhardt; R. Haller; P. König

    1987-01-01

    We present a randomized double-blind study on the efficacy of caroverine in the treatment of alcohol withdrawal symptoms. The group B Ca2+ channel blocking agent caroverine was tested against meprobamate in inpatient treatment of alcohol withdrawal. Patients of both groups were similar in age, weight, duration of drinking, ingested quantities of alcohol and intensity of withdrawal symptoms in both groups.

  1. Alcohol Facts

    MedlinePLUS

    ... page Alcohol Facts Drinks like beer, malt liquor, wine, and hard liquor contain alcohol. Alcohol is the ... alcohol in it than beer, malt liquor, or wine. These drink sizes have about the same amount ...

  2. Modulation of penetrance by the wild-type allele in dominantly inherited erythropoietic protoporphyria and acute hepatic porphyrias.

    PubMed

    Gouya, Laurent; Puy, Hervé; Robreau, Anne-Marie; Lyoumi, Said; Lamoril, Jérome; Da Silva, Vasco; Grandchamp, Bernard; Deybach, Jean-Charles

    2004-02-01

    We have recently demonstrated that in an autosomal dominant porphyria, erythropoietic protoporphyria (EPP), the coinheritance of a ferrochelatase (FECH) gene defect and of a wild-type low-expressed FECH allele is generally involved in the clinical expression of EPP. This mechanism may provide a model for phenotype modulation by minor variations in the expression of the wild-type allele in the other three autosomal dominant porphyrias that exhibit incomplete penetrance: acute intermittent porphyria (AIP), variegata porphyria (VP) and hereditary coproporphyria (HC), which are caused by partial deficiencies of hydroxy-methyl bilane synthase (HMBS), protoporphyrinogen oxidase (PPOX) and coproporphyrinogen oxidase (CPO), respectively. Given the dominant mode of inheritance of EPP, VP, AIP and HC, we first confirmed that the 200 overtly porphyric subjects (55 EPP, 58 AIP, 56 VP; 31 HC) presented a single mutation restricted to one allele (20 novel mutations and 162 known mutations). We then analysed the available single-nucleotide polymorphisms (SNPs) present at high frequencies in the general population and spreading throughout the FECH, HMBS, PPOX and the CPO genes in four case-control association studies. Finally, we explored the functional consequences of polymorphisms on the abundance of wild-type RNA, and used relative allelic mRNA determinations to find out whether low-expressed HMBS, PPOX and the CPO alleles occur in the general population. We confirm that the wild-type low-expressed allele phenomenon is usually operative in the mechanism of variable penetrance in EPP, but conclude that this is not the case in AIP and VP. For HC, the CPO mRNA determinations strongly suggest that normal CPO alleles with low-expression are present, but whether this low-expression of the wild-type allele could modulate the penetrance of a CPO gene defect in HC families remains to be ascertained. PMID:14669009

  3. Non-Alcoholic Fatty Liver Disease (NAFLD)

    MedlinePLUS

    ... occur with resultant hepatitis called non-alcoholic steatohepatitis (NASH). This condition can lead to liver damage with ... 10-40% of adults in the United States. NASH is present in 2 to 5 percent of ...

  4. 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 ...

  5. 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 ...

  6. Lesser celandine (pilewort) induced acute toxic liver injury: The first case report worldwide.

    PubMed

    Yilmaz, Bulent; Yilmaz, Bar??; Akta?, Bora; Unlu, Ozan; Roach, Emir Charles

    2015-02-27

    Lesser celandine, also known as Ranunculus ficaria, is a herbaceous perennial plant that commonly utilizes piles and is taken either internally or used externally. The causality assessment of several reports provided evidence for the existence of Greater Celandine hepatotoxicity. However, there hasn't been any case report published thus far, about lesser celandine induced liver injury. Here, we present a case of 36-year-old woman admitted to the hospital with acute hepatitis and jaundice on her sclera with no history of drug abuse or alcohol consumption. However, the patient had a recent history of lesser celandine extract consumption for hemorrhoids, for about 10 d, prior to the admission. Viral hepatitis, autoimmune hepatitis, and drug induced toxic hepatitis were ruled out by further imaging studies and laboratory analysis. Using the Council for International Organizations of Medical Sciences scale, the type of liver injury was assumed as hepatocellular and was scored as 7 which shows probable causality. Immediate discontinuation of lesser celandine extract resulted in rapid decrease of the elevated enzymes. Herbs have been reported to cause liver injury and therefore should be suspected in the case of acute hepatitis with an unknown etiology. This case is important to be the first to explain hepatotoxicity caused by lesser celandine. Physicians should consider lesser celandine as a causative agent for hepatotoxicity. PMID:25729484

  7. Ethanol Extract of Fructus Schisandrae Decreases Hepatic Triglyceride Level in Mice Fed with a High Fat\\/Cholesterol Diet, with Attention to Acute Toxicity

    Microsoft Academic Search

    Si-Yuan Pan; Zhi-Ling Yu; Hang Dong; Chun-Jing Xiang; Wang-Fun Fong

    Effects of the ethanol extract of Fructus Schisandrae (EtFSC) on serum and liver lipid contents were investigated in mice fed with high fat\\/cholesterol (HFC) diet for 8 or 15 days. The induc- tion of hypercholesterolemia by HFC diet caused significant increases in serum and hepatic total cholesterol (TC) levels (up to 62% and 165%, respectively) and hepatic triglyceride (TG) levels

  8. Alcohol Impairment and Social Drinking.

    ERIC Educational Resources Information Center

    Bates, Marsha E.

    Cognitive abilities of social drinkers are generally thought to be affected by alcohol only during acute intoxication, but several studies suggest that sober-state performance may be affected by the quantity of alcohol consumed per drinking episode. Although the findings regarding sober-state mental deficits in social drinkers are inconclusive,…

  9. What I Need to Know about Hepatitis C

    MedlinePLUS

    ... person sharing spoons, forks, and other eating utensils drinking water or eating food A baby cannot get hepatitis ... with the hepatitis C virus. Early diagnosis and treatment of chronic hepatitis C can ... a healthy diet. Avoid drinking alcohol, which can harm the liver. Talk with ...

  10. Carbohydrate deficient transferrin and alcoholism

    PubMed Central

    Solomons, Hilary Denis

    2012-01-01

    Alcohol abuse is an important public health problem, with major implications in patients with a pre-existing liver pathology of viral origin. Hepatitis C, for example, is one of the diseases in which alcohol consumption can lead to the transition from a fairly benign outline to a potentially life-threatening liver disease. Alcohol abuse is usually identified on the basis of clinical judgment, alcoholism related questionnaires, laboratory tests and, more recently, biomarkers. Also on this list of tests, carbohydrate deficient transferrin (CDT) is widely available and useful for determining recent alcohol consumption, particularly when corroborated with elevation of other liver-associated enzymes. Clinicians should be aware of the indications and limitations of this test in order to better evaluate alcohol consumption in their patients. PMID:24432265

  11. Alcohol myopia and goal commitment

    PubMed Central

    Sevincer, A. Timur; Oettingen, Gabriele

    2014-01-01

    According to alcohol myopia theory, acute alcohol consumption leads people to disproportionally focus on the salient rather than the peripheral aspects of a situation. We summarize various studies exploring how myopic processes resulting from acute alcohol intake affect goal commitment. After consuming alcohol student participants felt strongly committed to an important personal goal even though they had low expectations of successfully attaining the goal. However, once intoxicated participants were sober again (i.e., not myopic anymore) they failed to act on their goal commitment. In line with alcohol myopia theory, strong goal commitment as a result of alcohol intake was mediated by intoxicated (vs. sober) participants disproportionally focusing on the desirability rather than the feasibility of their goal. Further supporting alcohol myopia theory, when the low feasibility of attaining a particular goal was experimentally made salient (either explicitly or implicitly by subliminal priming), intoxicated participants felt less committed than those who consumed a placebo. We discuss these effects of acute alcohol intake in the context of research on the effects of chronic alcohol consumption on goal commitment. PMID:24624106

  12. 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 ...

  13. 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 ...

  14. 15-Deoxy-?12,14-prostaglandin J2 Reduces Liver Impairment in a Model of ConA-Induced Acute Hepatic Inflammation by Activation of PPAR? and Reduction in NF-?B Activity

    PubMed Central

    Chen, Kan; Li, Jingjing; Wang, Junshan; Xia, Yujing; Dai, Weiqi; Wang, Fan; Shen, Miao; Cheng, Ping; Zhang, Yan; Wang, Chengfen; Yang, Jing; Zhu, Rong; Zhang, Huawei; Zheng, Yuanyuan; Lu, Jie; Fan, Zhuoyi; Zhou, Yingqun; Guo, Chuanyong

    2014-01-01

    Objective. 15-Deoxy-?12,14-prostaglandin J2 (15d-PGJ2) reduces inflammation and has been identified as an anti-inflammatory prostaglandin in numerous animal models. In this study, we investigated both effects of 15d-PGJ2 and its protection mechanism in concanavalin A- (ConA-) induced autoimmune hepatitis in mice. Materials and Methods. In vivo, Balb/C mice were injected with ConA (25?mg/kg) to induce acute autoimmune hepatitis, and 15d-PGJ2 (10??g or 25??g) was administered 1?h before the ConA injection. The histological grade, proinflammatory cytokine levels, and NF-?B and PPAR? activity were determined 6, 12, and 24?h after the ConA injection. In vitro, LO2 cells and RAW264.7 cells were pretreated with 15d-PGJ2 (2??M) 1?h before the stimulation with ConA (30??g/mL). The NF-?B and PPAR? activity were determined 30?min after the ConA administration. Results. Pretreatment with 15d-PGJ2 reduced the pathological effects of ConA-induced autoimmune hepatitis and significantly reduced the levels of cytokines after injection. 15d-PGJ2 activated PPAR?, blocked the degradation of I?B?, and inhibited the translocation of NF-?B into the nucleus. Conclusion. These results indicate that 15d-PGJ2 protects against ConA-induced autoimmune hepatitis by reducing proinflammatory cytokines. This reduction in inflammation may correlate with the activation of PPAR? and the reduction in NF-?B activity. PMID:25120564

  15. Trouble with Bleeding: Risk Factors for Acute Hepatitis C among HIV-Positive Gay Men from Germany---A Case-Control Study

    Microsoft Academic Search

    Axel J. Schmidt; Jürgen K. Rockstroh; Martin Vogel; Matthias An der Heiden; Armin Baillot; Ivanka Krznaric; Doris Radun; Xia Jin

    2011-01-01

    ObjectivesTo identify risk factors for hepatitis C among HIV-positive men who have sex with men (MSM), focusing on potential sexual, nosocomial, and other non-sexual determinants.BackgroundOutbreaks of hepatitis C virus (HCV) infections among HIV-positive MSM have been reported by clinicians in post-industrialized countries since 2000. The sexual acquisition of HCV by gay men who are HIV positive is not, however, fully

  16. Simultaneous Detection of Immunoglobulin A (IgA) and IgM Antibodies against Hepatitis E Virus (HEV) Is Highly Specific for Diagnosis of Acute HEV Infection

    Microsoft Academic Search

    Masaharu Takahashi; Shigeyuki Kusakai; Hitoshi Mizuo; Kazuyuki Suzuki; Kuniko Fujimura; Kazuo Masuko; Yoshiki Sugai; Tatsuya Aikawa; Tsutomu Nishizawa; Hiroaki Okamoto

    2005-01-01

    Serum samples collected from 68 patients (age, mean the standard deviation (SD), 56.3 12.8 years) at admission who were subsequently molecularly diagnosed as having hepatitis E and from 2,781 individuals who were assumed not to have been recently infected with hepatitis E virus (HEV; negative controls; 52.9 18.9 years), were tested for immunoglobulin M (IgM) and IgA classes of antibodies

  17. Effects of Protein-Free Diet and Food Deprivation on Hepatic Rhodanese Activity, Serum Proteins and Acute Cyanide Lethality in Mice12

    Microsoft Academic Search

    JOSEPH V. RUTKOWSKI; B. D. ROEBUCK; ROGER P. SMITH

    This study was undertaken to evaluate changes in hepatic and extra- hepatic cyanide detoxication resulting from nutritional deficits and any parallel changes in cyanide sensitivity. Male CD-I mice were fed control diet, control diet in reduced quantities or protein-free diet. After 14 d body weight and relative liver size were lower in the protein-free diet and the food-deprived groups than

  18. [Alcohol use in France].

    PubMed

    Beck, François; Richard, Jean-Baptiste

    2014-10-01

    Alcohol consumption has regularly decreased in France since the 1950s, essentially in connection with the decrease of wine consumption, with disaffection for the "table wine", for the benefit of better quality wines that are drunk in lesser quantity. France is still part of the most alcohol drinking countries in the European Union but is no longer situated at the very top of the ranking. General population surveys results tend to confirm the evolution of sale of alcohol: since 1992, among 15-75 years old, alcohol daily users proportion was divided by two, from 24% in 1992 to 11% in 2010, currently replaced by a more occasional use. We indeed observe in the general population a profile of young adults having a strong and punctual consumption, and an older profile of less important but regular consumption. The proportion of problematic alcohol users remains stable, concerning approximately a person on 10 in the adult population. The part of persons who declared they have drunk six glasses or more during the same occasion at least once a month during the last twelve months increased from 15% in 2005 to 18% in 2010. Binge drinking and the frequency of drunkenness have increased among teenagers and young adults these last years. These behaviors can lead to short term risks, such as accidents, undergone violence, unwanted or unprotected sexual intercourse, even coma, whereas chronic alcohol use can lead to numerous hepatic, cardiovascular and neuropsychiatric complications, as well as cancers. With such sanitary consequences, alcohol is a major risk factor of avoidable morbidity and premature mortality. The beneficial effect that seems to have a moderate consumption of alcohol on the risk of death by cardiovascular diseases has brought about recurring scientific controversies. However, its major noxious effects in terms of non-transmitted diseases should remain the major point in public health decisions on alcoholization. PMID:24994508

  19. Diagnosis of alcoholic liver disease

    PubMed Central

    Torruellas, Cara; French, Samuel W; Medici, Valentina

    2014-01-01

    Alcohol is a hepatotoxin that is commonly consumed worldwide and is associated with a spectrum of liver injury including simple steatosis or fatty liver, alcoholic hepatitis, fibrosis, and cirrhosis. Alcoholic liver disease (ALD) is a general term used to refer to this spectrum of alcohol-related liver injuries. Excessive or harmful alcohol use is ranked as one of the top five risk factors for death and disability globally and results in 2.5 million deaths and 69.4 million annual disability adjusted life years. All patients who present with clinical features of hepatitis or chronic liver disease or who have elevated serum elevated transaminase levels should be screened for an alcohol use disorder. The diagnosis of ALD can generally be made based on history, clinical and laboratory findings. However, the diagnosis of ALD can be clinically challenging as there is no single diagnostic test that confirms the diagnosis and patients may not be forthcoming about their degree of alcohol consumption. In addition, clinical findings may be absent or minimal in early ALD characterized by hepatic steatosis. Typical laboratory findings in ALD include transaminase levels with aspartate aminotransferase greater than alanine aminotransferase as well as increased mean corpuscular volume, gamma-glutamyltranspeptidase, and IgA to IgG ratio. In unclear cases, the diagnosis can be supported by imaging and liver biopsy. The histological features of ALD can ultimately define the diagnosis according to the typical presence and distribution of hepatic steatosis, inflammation, and Mallory-Denk bodies. Because of the potential reversible nature of ALD with sobriety, regular screening of the general population and early diagnosis are essential. PMID:25206273

  20. [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

  1. Increased hepatocyte CYP2E1 expression in a rat nutritional model of hepatic steatosis with inflammation

    Microsoft Academic Search

    GC Farrell; C Liddle

    1996-01-01

    BACKGROUND & AIMS: Nonalcoholic steatohepatitis is morphologically identical to alcoholic hepatitis and has multiple etiologic associations and an unknown pathogenesis. The present study used a rat nutritional model of hepatic steatosis with inflammation to test the hypothesis that induction of the alcohol-inducible hepatic cytochrome P450 (CYP) 2E1 is associated with production of steatohepatitis. METHODS: Rats received a diet devoid of

  2. Alcohol Testing

    Microsoft Academic Search

    Steve C. Kazmierczak; Hassan M. E. Azzazy

    Ethanol, commonly also referred to as alcohol, is widely used as well as abused, and measurement of alcohol is a common test\\u000a in clinical toxicology and forensic laboratories. Although blood alcohol measurement is most commonly used, alcohol can also\\u000a be measured in breath, urine, saliva and vitreous humor. Whole blood alcohol levels are lower than serum alcohol levels, and\\u000a the

  3. Pharmacokinetic and pharmacodynamic drug interactions with ethanol (alcohol).

    PubMed

    Chan, Lingtak-Neander; Anderson, Gail D

    2014-12-01

    Ethanol (alcohol) is one of the most widely used legal drugs in the world. Ethanol is metabolized by alcohol dehydrogenase (ADH) and the cytochrome P450 (CYP) 2E1 drug-metabolizing enzyme that is also responsible for the biotransformation of xenobiotics and fatty acids. Drugs that inhibit ADH or CYP2E1 are the most likely theoretical compounds that would lead to a clinically significant pharmacokinetic interaction with ethanol, which include only a limited number of drugs. Acute ethanol primarily alters the pharmacokinetics of other drugs by changing the rate and extent of absorption, with more limited effects on clearance. Both acute and chronic ethanol use can cause transient changes to many physiologic responses in different organ systems such as hypotension and impairment of motor and cognitive functions, resulting in both pharmacokinetic and pharmacodynamic interactions. Evaluating drug interactions with long-term use of ethanol is uniquely challenging. Specifically, it is difficult to distinguish between the effects of long-term ethanol use on liver pathology and chronic malnutrition. Ethanol-induced liver disease results in decreased activity of hepatic metabolic enzymes and changes in protein binding. Clinical studies that include patients with chronic alcohol use may be evaluating the effects of mild cirrhosis on liver metabolism, and not just ethanol itself. The definition of chronic alcohol use is very inconsistent, which greatly affects the quality of the data and clinical application of the results. Our study of the literature has shown that a significantly higher volume of clinical studies have focused on the pharmacokinetic interactions of ethanol and other drugs. The data on pharmacodynamic interactions are more limited and future research addressing pharmacodynamic interactions with ethanol, especially regarding the non-central nervous system effects, is much needed. PMID:25267448

  4. COMBINING THE AUDIT QUESTIONNAIRE AND BIOCHEMICAL MARKERS TO ASSESS ALCOHOL USE AND RISK OF ALCOHOL WITHDRAWAL IN MEDICAL INPATIENTS

    Microsoft Academic Search

    JONATHAN M. DOLMAN; NEIL D. HAWKES

    2005-01-01

    Aims: Alcohol consumption is often under-reported in patients admitted to general hospitals with acute illness. For alcohol-dependent individuals hospital admission results in an enforced period of abstinence with potential alcohol withdrawal symp- toms, and possible life threatening complications. Early detection of alcohol use is therefore beneficial to patients and health services. The purpose of this study was to investigate the

  5. Protective effect of alcoholic extract of Entada pursaetha DC. against CCl4-induced hepatotoxicity in rats.

    PubMed

    Gupta, Gaurav; More, Amar Sunil; Kumari, Rashmi Rekha; Lingaraju, Madhu Cholenahalli; Kumar, Dhirendra; Kumar, Dinesh; Mishra, Santosh Kumar; Tandan, Surender Kumar

    2014-03-01

    The alcoholic extract of stem of E. pursaetha (PSE, 30, 100, 300 mg/kg body weight, po for 7 days) showed hepatoprotective activity against CCl4 (2 mL/kg body weight, ip)-induced hepatotoxicity. The extract exhibited a significant dose-dependent hepatoprotective effect comparable to standard drug silymarin, by preventing increase in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, and total bilirubin, lactate dehydrogenase; by lowering hepatic levels of malonaldehyde, nitrate-nitrite, myeloperoxidase activity; enhancing activities of antioxidant enzymes, superoxide dismutase, catalase and increasing reduced glutathione levels in liver, which suggests the antioxidant property of PSE. Histopathological studies also supported the above biochemical parameters. The results suggested that alcoholic extract of E. pursaetha possesses significant hepatoprotective activity in CCl4-induced acute hepatotoxicity in rats and this is likely to be mediated through its antioxidant activities. PMID:24669663

  6. SEX HORMONES DURING ALCOHOL WITHDRAWAL: A LONGITUDINAL STUDY OF 29 MALE ALCOHOLICS DURING DETOXIFICATION

    Microsoft Academic Search

    JAAN RUUSA; BO BERGMAN; MONA-LISA SUNDELL

    It is a well-known fact that alcohol affects sex hormone levels in males. Even in the absence of liver dysfunction, there is still a direct toxic effect of ethanol on testosterone synthesis resulting in acutely decreased values. This study is based on 29 male alcoholics without severe signs of liver disease treated on the alcohol detoxification ward at Huddinge hospital

  7. Does Preinjury Alcohol Use or Blood Alcohol Level Influence Cognitive Functioning After Traumatic Brain Injury?

    Microsoft Academic Search

    Aaron P. Turner; Daniel R. Kivlahan; Carl T. Rimmele; Charles H. Bombardier

    2006-01-01

    Objective: To examine the relations among preinjury alcohol use patterns and admission blood alcohol level (BAL) and postinjury cognitive functioning among individuals with recent TBI. Design: Cohort survey with chart review and follow-up cognitive assessment. Setting: Acute inpatient rehabilitation program in a Level I trauma center. Participants: 124 consecutive initial admissions meeting inclusion criteria. Measures: Admission BAL, preinjury alcohol consumption,

  8. 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

  9. Review article Zoonotic hepatitis E: animal reservoirs and emerging risks

    E-print Network

    Paris-Sud XI, Université de

    Review article Zoonotic hepatitis E: animal reservoirs and emerging risks Nicole PAVIO 1*, Xiang; accepted 1 April 2010) Abstract ­ Hepatitis E virus (HEV) is responsible for enterically-transmitted acute hepatitis in humans with two distinct epidemiological patterns. In endemic regions, large waterborne

  10. 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

  11. The Antibody Response Following Hepatitis A Infection

    Microsoft Academic Search

    Stephen A. Locarnini; Allan A. Ferris; Noreen I. Lehmann; Ian D. Gust

    1977-01-01

    Summary A specific IgM response to hepatitis A virus was detected in sera from patients suffering acute hepatitis A infection. The presence of virus-specific IgM in 19S components of acute and early convalescent phase sera was detected by immune electron microscopy and solid-phase radioimmunoassay. The presence of virus-specific IgM in whole serum specimens was demonstrated by indirect immunoferritin labeling. Following

  12. Projecting future complications of chronic hepatitis C in the United States

    Microsoft Academic Search

    Gary L. Davis; James E. Albright; Suzanne F. Cook; Daniel M. Rosenberg

    2003-01-01

    Chronic hepatitis C virus (HCV) infection is common and often results in slowly progressive liver disease. Although acute hepatitis C is now uncommon, most patients with acute infection have developed chronic hepatitis, and, therefore, the pool of infected patients is large. We used a modification of a previously described natural history model for HCV infection to project the number of

  13. 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 ...

  14. 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 ...

  15. Concurrent Acute Necrotizing Adenovirus Hepatitis and Enterocolitis in an Adult Patient After Double Cord Blood Stem Cell Transplant for Refractory Crohn's Disease.

    PubMed

    Lo, Amy A; Lo, Edward C; Rao, M Sambasivia; Yang, Guang-Yu

    2015-08-01

    It has been recently recognized that adenovirus is a pathogen with high morbidity and mortality among immunocompromised patients, particularly after solid organ or stem cell transplant. Confluent necrotizing hepatitis secondary to adenovirus infection alone or together with other organ involvement is extremely rare. There are only 32 cases of confluent necrotizing hepatitis reported in adults since 1960 and most occur after iatrogenic immunosuppression for bone marrow or solid organ transplantation or in other states of immunosuppression, including acquired immunodeficiency syndrome or chemotherapy treatment. We present the first case of concurrent adenovirus-induced necrotizing hepatitis and enterocolitis in an adult patient after double cord stem cell transplant for refractory Crohn's disease. Additionally, we report the imaging and morphologic findings and discuss the potential significance of morphology and immunohistochemistry as a practical approach for identifying adenovirus. PMID:25998316

  16. Role of GABA(B) receptor in alcohol dependence: reducing effect of baclofen on alcohol intake and alcohol motivational properties in rats and amelioration of alcohol withdrawal syndrome and alcohol craving in human alcoholics.

    PubMed

    Colombo, Giancarlo; Addolorato, Giovanni; Agabio, Roberta; Carai, Mauro A M; Pibiri, Fabio; Serra, Salvatore; Vacca, Giovanni; Gessa, Gian Luigi

    2004-01-01

    The present paper describes the results of recent preclinical and clinical studies conducted in this laboratory in order to characterize the anti-alcohol properties of the GABA(B) receptor agonist, baclofen. At a preclinical level, the repeated administration of non-sedative doses of baclofen dose-dependently suppressed the acquisition and maintenance of alcohol drinking behavior in selectively bred Sardinian alcohol-preferring (sP) rats tested under the homecage, 2-bottle "alcohol vs water" choice regimen. Acute injection of baclofen completely blocked the temporary increase in voluntary alcohol intake occurring after a period of alcohol abstinence (the so-called alcohol deprivation effect, which models alcohol relapses in human alcoholics). Acute treatment with baclofen also dose-dependently suppressed extinction responding for alcohol (an index of motivation to consume alcohol) in sP rats trained to lever-press for oral alcohol self-administration. Taken together, these results suggest the involvement of the GABA(B) receptor in the neural substrate mediating alcohol intake and alcohol motivational properties in an animal model of excessive alcohol consumption. Further, acutely administered baclofen dose-dependently reduced the severity of alcohol withdrawal signs in Wistar rats made physically dependent upon alcohol. Preliminary clinical surveys suggest that the anti-alcohol properties of baclofen observed in rats may generalize to human alcoholics. Indeed, a double-blind survey demonstrated that repeated daily treatment with baclofen was associated, when compared to placebo, with a higher percentage of subjects totally abstinent from alcohol and a higher number of days of total abstinence. Treatment with baclofen also suppressed the number of daily drinks and decreased the obsessive and compulsive components of alcohol craving. Finally, a single non-sedative dose of baclofen resulted in the rapid disappearance of alcohol withdrawal symptomatology, including delirium tremens, in alcohol-dependent patients. In both clinical studies, baclofen was well tolerated with minimal side effects. These results suggest that baclofen may represent a potentially effective medication in the treatment of alcohol-dependent patients. PMID:15545024

  17. Hepatic Transcriptome Analysis of Hepatitis C Virus Infection in Chimpanzees Defines Unique Gene Expression Patterns Associated with Viral Clearance

    Microsoft Academic Search

    Santosh Nanda; Michael B. Havert; Gloria M. Calderón; Michael Thomson; Christian Jacobson; Daniel Kastner; T. Jake Liang; Fu-Sheng Wang

    2008-01-01

    Hepatitis C virus infection leads to a high rate of chronicity. Mechanisms of viral clearance and persistence are still poorly understood. In this study, hepatic gene expression analysis was performed to identify any molecular signature associated with the outcome of hepatitis C virus (HCV) infection in chimpanzees. Acutely HCV-infected chimpanzees with self-limited infection or progression to chronicity were studied. Interferon

  18. In vivo relationship between monoamine oxidase type B and alcohol dehydrogenase: effects of ethanol and phenylethylamine

    SciTech Connect

    Aliyu, S.U.; Upahi, L.

    1988-01-01

    The role of acute ethanol and phenylethylamine on the brain and platelet monoamine oxidase activities, hepatic cytosolic alcohol dehydrogenase, redox state and motor behavior were studied in male rats. Ethanol on its own decreased the redox couple ratio, as well as, alcohol dehydrogenase activity in the liver while at the same time it increased brain and platelet monoamine oxidase activity due to lower Km with no change in Vmax. The elevation in both brain and platelet MAO activity was associated with ethanol-induced hypomotility in the rats. Co-administration of phenylethylamine and ethanol to the animals, caused antagonism of the ethanol-induced effects described above. The effects of phenylethylamine alone, on the above mentioned biochemical and behavioral indices, are more complex. Phenylethylamine on its own, like ethanol, caused reduction of the cytosolic redox, ratio and elevation of monoamine oxidase activity in the brain and platelets. However, in contrast to ethanol, this monoamine produced hypermotility and activation of the hepatic cytosolic alcohol dehydrogenase activity in the animals.

  19. 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 ...

  20. 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 ...

  1. 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

  2. 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 ...

  3. JAMA Patient Page: Alcohol Abuse and Alcoholism

    MedlinePLUS

    ... Medical Association JAMA PATIENT PAGE Alcohol Abuse and Alcoholism A buse of alcohol is a major cause ... by or worsened by the effects of alcohol. Alcoholism (alcohol dependence) is a more severe pattern of ...

  4. Current status and prospects of studies on human genetic alleles associated with hepatitis B virus infection

    Microsoft Academic Search

    Fu-Sheng Wang

    2003-01-01

    Abstract Chronic hepatitis B virus (HBV) infection can cause a broad spectrum diseases, including from asymptomatic HBV carriers or cryptic hepatitis, to acute hepatitis, chronic hepatitis, Liver cirrhosis and primary hepatocellular carcinoma. The variable pattern and clinical outcome of the infection were mainly determined by virological itself factors, host immunological factors and genetic factors as well as the experimental factors.

  5. Transgenic Expression of Aflatoxin Aldehyde Reductase (AKR7A1) Modulates Aflatoxin B1 Metabolism but not Hepatic Carcinogenesis in the Rat

    PubMed Central

    Roebuck, Bill D.; Johnson, Denise N.; Sutter, Carrie Hayes; Egner, Patricia A.; Scholl, Peter F.; Friesen, Marlin D.; Baumgartner, Karen J.; Ware, Nicholas M.; Bodreddigari, Sridevi; Groopman, John D.; Kensler, Thomas W.; Sutter, Thomas R.

    2009-01-01

    In both experimental animals and humans, aflatoxin B1 (AFB1) is a potent hepatic toxin and carcinogen against which a variety of antioxidants and experimental or therapeutic drugs (e.g., oltipraz, related dithiolethiones, and various triterpenoids) protect from both acute toxicity and carcinogenesis. These agents induce several hepatic glutathione S-transferases (GST) as well as aldo-keto reductases (AKR) which are thought to contribute to protection. Studies were undertaken in transgenic rats to examine the role of one inducible enzyme, AKR7A1, for protection against acute and chronic actions of AFB1 by enhancing detoxication of a reactive metabolite, AFB1 dialdehyde, by reduction to alcohols. The AFB1 dialdehyde forms adducts with protein amino groups by a Schiff base mechanism and these adducts have been theorized to be at least one cause of the acute toxicity of AFB1 and to enhance carcinogenesis. A liver-specific AKR7A1 transgenic rat was constructed in the Sprague-Dawley strain and two lines, AKR7A1Tg2 and AKR7A1Tg5, were found to overexpress AKR7A1 by 18- and 8-fold, respectively. Rates of formation of AFB1 alcohols, both in hepatic cytosols and as urinary excretion products, increased in the transgenic lines with AKR7A1Tg2 being the highest. Neither line offered protection against acute AFB1-induced bile duct proliferation, a functional assessment of acute hepatotoxicity by AFB1, nor did they protect against the formation of GST-P positive putative preneoplastic foci as a result of chronic exposure to AFB1. These results imply that the prevention of protein adducts mediated by AKR are not critical to protection against AFB1 tumorigenicity. PMID:19168568

  6. Acute Liver Failure Secondary to Niacin Toxicity

    PubMed Central

    Ellsworth, Marc A.; Anderson, Katelyn R.; Hall, David J.; Freese, Deborah K.; Lloyd, Robin M.

    2014-01-01

    A 17-year-old male was transferred to the pediatric intensive care unit for evaluation of acute liver failure. He was recently released from an alcohol treatment center with acute onset of chest pain. Cardiac workup was negative but he was found to have abnormal coagulation studies and elevated liver transaminases. Other evaluations included a normal toxicology screen and negative acetaminophen level. Autoimmune and infectious workups were normal providing no identifiable cause of his acute liver failure. He initially denied any ingestions or illicit drug use but on further query he admitted taking niacin in an attempt to obscure the results of an upcoming drug test. Niacin has been touted on the Internet as an aid to help pass urine drug tests though there is no evidence to support this practice. Niacin toxicity has been associated with serious multisystem organ failure and fulminant hepatic failure requiring liver transplantation. Pediatric providers should be aware of the risks associated with niacin toxicity and other experimental medical therapies that may be described on the Internet or other nonreputable sources. PMID:24711953

  7. [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

  8. Suppression of PGC-1? by Ethanol: Implications of Its Role in Alcohol Induced Liver Injury

    PubMed Central

    Chaung, Wayne W.; Jacob, Asha; Ji, Youxin; Wang, Ping

    2008-01-01

    Ethanol has been known to cause injury to the liver and other tissues; however the molecular factors responsible for alcohol induced liver injury has not been fully understood. Recent studies indicate that reactive oxygen species (ROS) may play an important role in alcohol induced liver injury. Peroxisome proliferator activated receptor-? (PPAR-?)-coactivator 1? (PGC-1?) has been shown to be involved in defenses against ROS by inducing many ROS-detoxifying enzymes. However, the role of PGC-1? in alcohol induced liver injury has not been elucidated. Therefore, in this study, we examined the effect of alcohol on gene and protein expression of PGC-1? in H4-IIE cells (in vitro) and hepatic tissues (in vivo) by real-time PCR and Western blot, respectively. Our results show that exposure to 500 mM ethanol in H4-IIE cells for 24 h significantly decreased both gene and protein expression of PGC-1?. PGC-1? gene expression was significantly decreased in cells exposed to 100 ng/ml LPS or 1% hypoxia for 24 h. In addition, PGC-1? gene and protein expressions were slightly lower in hepatic tissues of rats exposed to ethanol for 15 h, at the level equivalent to the 500 mM used in culture cells, in comparison to sham rats. In contrast, serum LDH and AST levels in ethanol exposed rats were 1.9 fold and 2.8 fold higher than that of sham rats, respectively, which suggest significant organ injury in these rats following ethanol exposure. Likewise, catalase, an enzyme that hydrolyzes peroxide to water, is significantly increased in ethanol exposed H4-IIE cells which further confirms ROS generation due to ethanol exposure. Thus, our results show that oxidative stress conditions such as acute alcohol consumption, LPS or hypoxia suppresses PGC-1? expression in the liver, thereby presumably downregulates pertinent ROS-scavenging enzymes and enhances liver injury. PMID:19079670

  9. [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

  10. 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

  11. Immune system and hepatitis B virus infection

    Microsoft Academic Search

    Chee-Kin Hui; George K. K. Lau

    2005-01-01

    The immune system plays an important role in determining the outcome of hepatitis B virus (HBV) infection. This is because recovery from of acute HBV infection is associated with a clear division in the profile of adaptive immune response. Multispecific antiviral CD4 and CD8 responses with a type 1 cytokine production can be observed in patients who recover from acute

  12. Polythiol-containing, recombinant mannosylated-albumin is a superior CD68+/CD206+ Kupffer cell-targeted nanoantioxidant for treatment of two acute hepatitis models.

    PubMed

    Maeda, Hitoshi; Hirata, Kenshiro; Watanabe, Hiroshi; Ishima, Yu; Chuang, Victor Tuan Giam; Taguchi, Kazuaki; Inatsu, Akihito; Kinoshita, Manabu; Tanaka, Motohiko; Sasaki, Yutaka; Otagiri, Masaki; Maruyama, Toru

    2015-02-01

    Since reactive oxygen species (ROS) derived from Kupffer cells (KC), especially CD68(+) KC, play a key role in the induction of hepatic oxidative stress and injuries, we developed a polythiolated- and mannosylated human serum albumin (SH-Man-HSA), which functions as a novel nanoantioxidant for delivering thiol to CD68(+) KC. In vitro electron paramagnetic resonance coupled with pharmacokinetics and immunohistochemical studies showed that SH-Man-HSA possessed powerful radical-scavenging activity and rapidly and selectively delivered thiols to the liver via mannose receptor (CD206) on CD68(+) cells. SH-Man-HSA significantly improved the survival rate of concanavalin-A (Con-A)-treated mice. Moreover, SH-Man-HSA exhibited excellent hepatoprotective functions, not by decreasing tumor necrosis factor or interferon-? production that is closely associated with Con-A-induced hepatitis, but by suppressing ROS production. Interestingly, the protective effect of SH-Man-HSA was superior to N-acetyl cysteine (NAC). This could be attributed to the difference in the inhibition of hepatic oxidative stress between the two antioxidants depending on their potential for thiol delivery to the liver. Similar results were also observed for acetaminophen (APAP)-induced hepatopathy models. Flow cytometric data further confirmed that an increase in F4/80(+)/ROS(+) cells was dramatically decreased by SH-Man-HSA. The administration of SH-Man-HSA at 4 hours following a Con-A or APAP injection also exhibited a profound hepatoprotective action against these hepatitis models, whereas this was not observed for NAC. It can be concluded therefore that SH-Man-HSA has great potential for use in a rescue therapy for hepatopathy as a nanoantioxidant because of its ability to efficiently and rapidly deliver thiols to CD68(+)/CD206(+) KC. PMID:25398242

  13. HIV Infection Accelerates Hepatitis C-Related Liver Fibrosis

    MedlinePLUS

    ... Prevention Research Training Treatment Research Trends and Statistics Drugs of Abuse Alcohol Amphetamines Bath Salts Club Drugs Cocaine Emerging ... this article APA style citation National Institute on Drug Abuse. HIV Infection Accelerates Hepatitis C–Related Liver Fibrosis ...

  14. 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: ...

  15. 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 ...

  16. 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

  17. Alcohol withdrawal

    Microsoft Academic Search

    Thomas A. Grieger; Deborah L. Warden; Cynthia Shappell

    1996-01-01

    Alcohol abuse or dependence is present in 13.6% of the general population and more than half of these individuals have another psychiatric disorder. Psychiatrists are increasingly involved in the management of alcohol withdrawal\\/detoxification. Although generally a safe procedure, patients must be carefully evaluated for comorbid conditions and for medical complications of prolonged alcohol use. Individuals who experience withdrawal symptoms require

  18. Alcoholics Anonymous

    Microsoft Academic Search

    Philip J. Flores

    1988-01-01

    This article explores some of the philosophical roots of Alcoholics Anonymous. Parallels between AA, existentialism and phenomenology are outlined. The success of AA is related to its ability to place the alcoholic's suffering within a meaningful paradigm and to require the alcoholic to accept responsibility and limitations while breaking the pattern of isolation and alienation.

  19. Understanding the Effects of Stress and Alcohol Cues on Motivation for Alcohol via Behavioral Economics

    PubMed Central

    Amlung, Michael; MacKillop, James

    2014-01-01

    Background Psychological stress and alcohol cues are common antecedents of both ongoing drinking and relapse. One candidate mechanism of risk from these factors is acute increases in craving, but experimental support for this hypothesis is mixed. Furthermore, the combination of stress and cues has been largely unstudied. The current study employed a behavioral economic approach to investigate the combined roles of psychosocial stress and alcohol cues on motivation for alcohol. Methods In a sample of 84 adult heavy drinkers, we examined the effects of an acute laboratory stress induction and an alcohol cue exposure on subjective craving and stress, arousal, and behavioral economic decision-making. Primary dependent measures included an intertemporal cross-commodity multiple choice procedure (ICCMCP), incorporating both price and delay elements; an alcohol purchase task (APT), measuring alcohol demand; and a monetary delay discounting task (DDT), measuring intertemporal choice. Results The stress induction significantly increased stress, craving, and the incentive value of alcohol on the ICCMCP and APT. Stress-related increases in value on the ICCMCP were mediated by increased alcohol demand. Exposure to alcohol cues only significantly affected craving, APT breakpoint, and arousal. Delay discounting was not affected by either stress or cues. Conclusions These results reveal unique behavioral economic dimensions of motivation for alcohol following acute stress and an alcohol cue exposure. More broadly, as the first application of this approach to understanding the role of stress in drug motivation, these findings support its utility and potential in future applications. PMID:24890323

  20. Alcohol and drug abuse in burn injuries

    Microsoft Academic Search

    A. Haum; W. Perbix; H. J. Häck; G. B. Stark; G. Spilker; M. Doehn

    1995-01-01

    Two studies are described in this paper. In the first study 225 acutely, severely burned patients were retrospectively investigated as to admission blood alcohol level and history of chronic alcohol abuse. The influence of further risk factors, circumstances and therapeutic data was studied, in particular the influence of gender, full-thickness burns, smoke inhalation injury, smoking, length of total and ICU

  1. Role of Alcohol Metabolism in Chronic Pancreatitis

    Microsoft Academic Search

    Alain Vonlaufen; Jeremy S. Wilson; Romano C. Pirola; Minoti V. Apte

    2007-01-01

    Alcohol abuse is the major cause of chronic inflammation of the pancreas (i.e., chronic pancreatitis). Although it has long been thought that alcoholic pancreatitis is a chronic disease from the outset, evidence is accumulating to indicate that chronic damage in the pancreas may result from repeated attacks of acute tissue inflammation and death (i.e., necroinflammation). Initially, research into the pathogenesis

  2. Short-term selection for acute ethanol tolerance and sensitization from an F 2 population derived from the high and low alcohol-sensitive selectively bred rat lines

    Microsoft Academic Search

    Richard A. Radcliffe; Pequita Bludeau; Xin-Sheng Deng; V. Gene Erwin; Richard A. Deitrich

    2007-01-01

    Previous studies have identified quantitative trait loci (QTL) in the inbred high and low alcohol-sensitive rat (IHAS1 and ILAS1) strains. The original development of the strains involved selection for ethanol sensitivity based on duration of the loss of the righting reflex (LORR) after a standard dose of ethanol. This paper confirms some of these QTL using a short-term selection procedure

  3. Quantitative analysis of transforming growth factor beta 1 mRNA in patients with alcoholic liver disease

    Microsoft Academic Search

    Wei-Xing Chen; You-Ming Li; Chao-Hui Yu; Wei-Min Cai; Min Zheng; Feng Chen

    AIM: To investigate the expression of the transforming growth factor beta 1(TGF- beta 1) mRNA in different stages of alcoholic liver disease (ALD) and its clinical value. METHODS: One hundred and seven male alcoholics were grouped by clinical findings into four groups: alcohol abusers without liver impairment (n=22), alcoholic steatosis (n=30); alcoholic hepatitis (n=31); and alcoholic cirrhosis(n=24). Using peripheral blood

  4. Alcoholics' Evaluations of Alcoholism Treatment

    Microsoft Academic Search

    Alisdair Mackenzie; Richard P. Allen

    2003-01-01

    A sample of alcoholics who have considerable experience as participants in alcoholism treatment are interviewed for their recommendations and criticisms of treatment. Inpatient Milieu and Alcoholics Anonymous were the most frequent choices of treatments considered beneficial. Among treatments not recommended were specific inpatient facilities. Our subjects' evaluations are compared with published reviews of treatment outcome studies. The relationships between treatment

  5. Facts about Alcohol and Alcoholism.

    ERIC Educational Resources Information Center

    Hall, Leonard C.

    Recognition of alcoholism as a treatable illness is a result of public education based on scientific facts. This publication, a digest of a more detailed survey of research about drinking and alcoholism, presents information about alcohol and its effects on individuals and society. It provides facts about the short-term and long-term effects of…

  6. Effectiveness of alcohol-based hand disinfectants in a public administration: Impact on health and work performance related to acute respiratory symptoms and diarrhoea

    Microsoft Academic Search

    Nils-Olaf Hübner; Claudia Hübner; Michael Wodny; Günter Kampf; Axel Kramer

    2010-01-01

    BACKGROUND: The economical impact of absenteeism and reduced productivity due to acute infectious respiratory and gastrointestinal disease is normally not in the focus of surveillance systems and may therefore be underestimated. However, large community studies in Europe and USA have shown that communicable diseases have a great impact on morbidity and lead to millions of lost days at work, school

  7. Pathophysiology of hepatitis C virus infection and related liver disease.

    PubMed

    Pawlotsky, Jean-Michel

    2004-02-01

    Hepatitis C virus (HCV) infects over 170 million people worldwide. Chronic infection occurs in 50-80% of cases and eventually leads to cirrhosis and hepatocellular carcinoma. The HCV lifecycle is only partly understood owing to the lack of a productive cell culture system. Several molecules have been implicated in the receptor complex at the surface of target cells, but the mode of HCV entry remains unknown. Persistent infection appears to be due to weak CD4+and CD8+ T-cell responses during acute infection, which fail to control viral replication. When chronic infection is established, HCV does not appear to be cytopathic. Liver lesions appear to result from locally driven immune responses, which are mainly non-specific. Local inflammation triggers fibrogenesis, in which hepatic stellate cells play a major role. Cirrhosis is facilitated by external factors, such as chronic alcohol consumption and viral co-infections. Patients with cirrhosis are at high risk of developing hepatocellular carcinoma. The role of HCV proteins in hepatocarcinogenesis is unknown. Further progress in our understanding of HCV infection and pathogenesis awaits the advent of new model systems and technologies. PMID:15036326

  8. Water Metabolism in Rats Subjected to Chronic Alcohol Administration

    Microsoft Academic Search

    Alexandr Parlesak; Claus Pohl; J. Christian Bode; Christiane Bode

    2004-01-01

    Aim: While the diuretic action of acute ingestion of alcohol has been studied extensively, the effect of chronic alcohol consumption has received less attention. The aim of the present study was to investigate the effect of chronic alcohol consumption on the balance of water intake and excretion and certain renal functions in rats during a period of 12 months. Animals

  9. Spin-trapping studies of hepatic free radicals formed following the acute administration of ethanol to rats: In vivo detection of 1-hydroxyethyl radicals with PBN

    Microsoft Academic Search

    L. A. Reinke; Y. Kotake; P. B. McCay; E. G. Janzen

    1991-01-01

    The generation of free radicals in rat liver following the acute oral administration of ethanol was studied with the spin-trapping method, using a deuterated derivative of phenyl-N-tert-butylnitrone (PBN-d14) as the spin-trapping agent. After administration of ethanol and PBN-d14 to rats, organic extracts of the liver were prepared and subjected to ESR spectroscopy. In the case of ethanol-treated rats, the ESR

  10. Alcohol Problems

    Microsoft Academic Search

    David C. Hodgins; Katherine Diskin; Jonathan N. Stea

    \\u000a Alcohol problems can be broadly defined as negative consequences that people experience as a result of their use of alcohol.\\u000a People may drink alcohol for a number of reasons: to promote feelings of relaxation, to increase feelings of sociability,\\u000a to elevate mood, to conform to social expectations, or to reduce feelings of stress (Anonymous, 2000). Information from the\\u000a US National

  11. IgA deposition in alcoholic liver disease.

    PubMed

    Goldin, R D; Cattle, S; Boylston, A W

    1986-11-01

    Immunoglobulin deposition in alcoholic and non-alcoholic liver disease was studied using an indirect immunoperoxidase technique. A continuous pattern of IgA deposition, with IgA outlining the sinusoids, was shown to be a specific and sensitive marker for liver disease caused by alcohol in both cirrhotic and non-cirrhotic livers. The sensitivity was lowest in cases of alcoholic disease showing fatty change alone. In one case it was possible to show the absence of IgA in liver disease caused by a drug, which was histologically indistinguishable from alcoholic hepatitis. PMID:3540014

  12. 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

  13. 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

  14. Focus On: Alcohol and the Immune System

    PubMed Central

    Molina, Patricia E.; Happel, Kyle I.; Zhang, Ping; Kolls, Jay K.; Nelson, Steve

    2010-01-01

    Alcohol abuse suppresses multiple arms of the immune response, leading to an increased risk of infections. The course and resolution of both bacterial and viral infections is severely impaired in alcohol-abusing patients, resulting in greater patient morbidity and mortality. Multiple mechanisms have been identified underlying the immunosuppressive effects of alcohol. These mechanisms involve structural host defense mechanisms in the gastrointestinal and respiratory tract as well as all of the principal components of the innate and adaptive immune systems, which are compromised both through alcohol’s direct effects and through alcohol-related dysregulation of other components. Analyses of alcohol’s diverse effects on various components of the immune system provide insight into the factors that lead to a greater risk of infection in the alcohol-abusing population. Some of these mechanisms are directly related to the pathology found in people with infections such as HIV/AIDS, tuberculosis, hepatitis, and pneumonia who continue to use and abuse alcohol. PMID:23579940

  15. [Metadoxine in alcohol-related pathology].

    PubMed

    Santoni, S; Corradini, P; Zocchi, M; Camarri, F

    1989-07-31

    Metadoxine is an active drug for treatment of acute and chronic alcohol intoxication, affecting both liver and brain function. The authors reviewed the international pharmacological and clinical literature on the drug which shows the potential usefulness of metadoxine in the treatment of alcohol-induced diseases. The case report concerns the results in 20 chronic alcoholics, admitted to the hospital for acute alcohol intake treated with metadoxine (one 500 mg tablet twice daily). Biohumoral hepatopathy parameters and clinical parameters of neuropsychic behaviour were examined simultaneously. Compared with a control group of patients undergoing traditional therapy (sedative and multi-vitamin drugs), metadoxine showed a significant improvement of the values of gamma-GT, GPT, blood ammonia, blood alcohol and of neuropsychic and behavioural parameters such as agitation, tremor, asterixis, sopor and depression. No side-effects or unfavourable reactions occurred during metadoxine treatment, which confirms the safety of this molecule. PMID:2529084

  16. Alcohol, affect, and the disinhibition of verbal behavior

    Microsoft Academic Search

    Thomas F. Babor; Steven Berglas; Jack H. Mendelson; James Ellingboe; Kenneth Miller

    1983-01-01

    A study was conducted to investigate the effects of acute alcohol administration on affective states and verbal behavior during the ascending and descending limbs of the blood alcohol curve. Sixteen male social drinkers were given alcohol (1.0 g\\/kg) or placebo in a double-blind crossover research design. Subjects tested while blood alcohol levels (BAL) were ascending close to peak concentration (0.11

  17. 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 ...

  18. 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 ...

  19. 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

  20. Alcoholics Anonymous

    Microsoft Academic Search

    Cathy Streifel; Heather Servanty-Seib

    2006-01-01

    The present paper offers two theories that help to explain why the 12-step program of Alcoholics Anonymous (AA) is such an effective intervention for recovering alcoholics, and provides directions for future research on AA. It is argued that Schlossberg's (1984) transition theory and Rando's (1995) theory of grief and mourning are applicable to the AA program because, as will be