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1

Acute Legionella pneumophila infection masquerading as acute alcoholic hepatitis  

PubMed Central

A middle-aged man had deteriorated rapidly in hospital after being misdiagnosed with acute alcoholic hepatitis. Acute Legionnaires disease (Legionellosis) was subsequently diagnosed on rapid antigen urinary testing and further confirmed serologically. This led to appropriate antibiotic treatment and complete clinical resolution. Physicians caring for patients with alcohol-related liver disease should consider Legionella pneumophila in their differential diagnosis even with a paucity of respiratory symptoms. PMID:23355576

Hunter, Jonathan Michael; Chan, Julian; Reid, Angeline Louise; Tan, Chistopher

2013-01-01

2

Pharmacotherapy of acute alcoholic hepatitis in clinical practice.  

PubMed

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

Abenavoli, Ludovico; Milic, Natasa; Rouabhia, Samir; Addolorato, Giovanni

2014-03-01

3

Prognosis and treatment of patients with acute alcoholic hepatitis.  

PubMed

Despite alcoholic hepatitis (AH) is the most acute manifestation of alcohol-related liver disease, its treatment remains controversial. Corticosteroids, given either as monotherapy or together with N-acetylecysteine, have been associated with a moderate short-term survival benefit in patients with severe disease. The Maddrey's discriminant function; Glasgow alcoholic hepatitis score; age, bilirubin, INR and creatinine score; and the Model for end-stage liver disease have been proposed for stratifying prognosis in AH enabling selection of the patients to treat. Definition of treatment non-responders using the Lille model after 7 days of therapy may prevent a detrimental impact of prolonged corticosteroids. Pentoxifylline is an effective alternative reducing the occurrence of hepatorenal syndrome. Emerging evidence supports use of liver transplantation in a strictly selected subset of corticosteroid non-responders. PMID:24716632

Papastergiou, Vassilios; Burroughs, Andrew K; Tsochatzis, Emmanuel A

2014-07-01

4

Alcoholic hepatitis  

PubMed Central

Alcoholic hepatitis (AH) is a clinical syndrome characterized by jaundice and liver failure that generally occurs after decades of harmful alcohol consumption. Less severe forms of acute AH (AAH) frequently respond to alcoholic abstinence; whereas severe AAHs are characterized by a poor prognosis: up to 40-60% of these patients die within six months. Glucocorticoids currently remain the mainstay for treating severe AAH in patients with Maddrey’s Discriminant Function score > 32. Standard contraindications include recent upper gastrointestinal bleeding, renal insufficiency and uncontrolled infections. The evaluation of concomitant viral infections (hepatitis C and B viruses) is mandatory. Liver transplantation (LT), in non-responders patients, is a possible therapeutic option for severe AAH, but it is rarely used because a 6-month abstinence period is required before listing for LT. Unfortunately, most of these patients die before the end of this sober period. In our opinion, in case of severe AAH and in case of patients with a good social support and without severe psychotic or personality disorders, the lack of pre-LT abstinence period alone should not be considered a hindrance to LT. PMID:23904876

Testino, G

2013-01-01

5

Alcoholic hepatitis.  

PubMed

Alcoholic hepatitis (AH) is a clinical syndrome characterized by jaundice and liver failure that generally occurs after decades of harmful alcohol consumption. Less severe forms of acute AH (AAH) frequently respond to alcoholic abstinence; whereas severe AAHs are characterized by a poor prognosis: up to 40-60% of these patients die within six months. Glucocorticoids currently remain the mainstay for treating severe AAH in patients with Maddrey's Discriminant Function score > 32. Standard contraindications include recent upper gastrointestinal bleeding, renal insufficiency and uncontrolled infections. The evaluation of concomitant viral infections (hepatitis C and B viruses) is mandatory. Liver transplantation (LT), in non-responders patients, is a possible therapeutic option for severe AAH, but it is rarely used because a 6-month abstinence period is required before listing for LT. Unfortunately, most of these patients die before the end of this sober period. In our opinion, in case of severe AAH and in case of patients with a good social support and without severe psychotic or personality disorders, the lack of pre-LT abstinence period alone should not be considered a hindrance to LT. PMID:23904876

Testino, G

2013-06-15

6

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

PubMed Central

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

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

7

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

PubMed

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

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

2014-10-28

8

Acute hepatic failure in the course of alcohol-paracetamol syndrome--case report.  

PubMed

Acetaminophen belongs to the antipyretic and analgesic drugs most commonly used all over the world. In western Europe, primarily in Great Britain, as well as in the US, increasing incidence of acute liver failure due to the overdose of the drug has been reported. The report presents a description of alcohol-paracetamol syndrome, which led to the development of acute hepatic failure with numerous complications. Intensive symptomatic and causal treatment with N-acetylcysteine resulted in complete recovery. PMID:15156605

Kozielewicz, Dorota; Dybowska, Dorota; Olczak, Anita; Nowak, Wojclech

2003-08-01

9

Alcoholic hepatitis: current management.  

PubMed

Alcoholic hepatitis is an acute manifestation of alcoholic liver disease with mortality as high as 40-50% in severe cases. Patients usually have a history of prolonged alcohol abuse with or without a known history of liver disease. Although there is significant range in severity at presentation, patients with severe alcoholic hepatitis typically present with anorexia, fatigue, fever, jaundice, and ascites. The use of either pentoxifylline or corticosteroids in those with severe disease (Maddrey's discriminate function >32) has significant mortality benefit. The addition of N-acetylcysteine to corticosteroids decreases the incidences of hepatorenal syndrome, infection, and short-term mortality, but does not appear to significantly affect 6-month mortality. Nutritional support with high-calorie, high-protein diet is recommended in all patients screening positive for malnutrition. Liver transplantation for a highly selected group of patients with severe alcoholic hepatitis may be an option in the future, but is not currently recommended or available at most transplant institutions. PMID:24798996

Spengler, Erin K J; Dunkelberg, Jeffrey; Schey, Ron

2014-10-01

10

Management of alcoholic hepatitis: Current concepts  

PubMed Central

Alcoholic hepatitis is a devastating form of acute liver injury seen in chronic alcohol abusers with significant morbidity and mortality. It is a multisystem disease that is precipitated by ingesting large quantities of alcohol with genetic and environmental factors playing a role. Prognostic criteria have been developed to predict disease severity and these criteria can serve as indicators to initiate medical therapy. Primary therapy remains abstinence and supportive care, as continued alcohol abuse is the most important risk factor for disease progression. The cornerstone of supportive care remains aggressive nutritional support, and although acute alcoholic hepatitis has been extensively studied, few specific medical therapies have been successful. Corticosteroids remain the most effective medical therapy available in improving short term survival in a select group of patients with alcoholic hepatitis; however, the long-term outcome of drug therapies is still not entirely clear and further clinical investigation is necessary. While liver transplantation for acute alcoholic hepatitis have demonstrated promising results, this practice remains controversial and has not been advocated universally, with most transplant centers requiring a prolonged period of abstinence before considering transplantation. Extracorporeal liver support devices, although still experimental, have been developed as a form of liver support to give additional time for liver regeneration. These have the potential for a significant therapeutic option in the future for this unfortunately dreadful disease. PMID:23355911

Karsan, Hetal A; Parekh, Samir

2012-01-01

11

Alcoholic hepatitis: Prognosis and treatment.  

PubMed

Alcoholic hepatitis (AH) is a type of acute-on-chronic liver failure and is the most severe form of alcoholic liver disease. AH occurs in patients with heavy alcohol abuse and underlying liver disease. In its severe form, AH carries a poor short-term prognosis. Although the existence of AH can be strongly suspected based on clinical and biochemical criteria, a definitive diagnosis requires a liver biopsy. There is a clear need to develop non-invasive markers for these patients. The prognosis of patients with AH can be established by different score systems (Maddrey's DF, ABIC, MELD and Glasgow). Recently, a histological scoring system able to estimate prognosis has been developed (Alcoholic Hepatitis Histological Score - AHHS). The management of patients with AH has changed little in the last few decades. In patients with severe form of AH, prednisolone and pentoxifylline are the first line therapy. Unfortunately, many patients do not respond and novel targeted therapies are urgently needed. Current research is aimed at identifying the main disease drivers and to develop animal models of true AH. For non-responders to medical therapy, the only curative option is to perform a salvage liver transplantation. This particular indication of liver transplantation is currently under debate and prospective studies should evaluate the specific patient evaluation and selection criteria. PMID:24656653

Casanova, Jennifer; Bataller, Ramón

2014-04-01

12

Acute alcohol intoxication.  

PubMed

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

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

2008-12-01

13

4 Acute hepatitis C  

Microsoft Academic Search

Acute hepatitis C is usually a sub-clinical disease, thus it is not included in the differential diagnosis of patients with acute disease. Making the diagnosis is also diffi cult because the virus antibodies appear at later stages and many even be negative even if the patient has symptoms; at this point the diagnosis of the disease could be made with

Jay H. Hoofnagle; JUAN CARLOS RESTREPO; John Jaime; Juan Carlos; Restrepo Gutiérrez; Gutiérrez Calle

2000-01-01

14

The hepatic-arterial/portal-venous scintiangiogram in alcoholic hepatitis  

SciTech Connect

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.

Stewart, C.; Sakimura, I.; Siegel, M.E.; Harley, H.; Lee, K.

1984-01-01

15

Hyperbilirubinaemia and haemolytic anaemia in acute alcoholic hepatitis: there's oil in them thar veins.  

PubMed

A Caucasian woman in her late 30s was evaluated after a period of binge drinking and found to have hyperbilirubinaemia for which she was referred for consideration of cholecystectomy. After exclusion of other possibilities, Zieve's syndrome was diagnosed. This is a condition of hyperbilirubinaemia, Coombs' negative haemolytic anaemia and hyperlipidaemia associated with alcoholism. Abstinence from alcohol remains the only known effective treatment, and appreciation of the entity can prevent unnecessary biliary procedures. The patient improved with supportive measures and was discharged in stable condition. PMID:24748143

Hashmi, Salman; Allison, Michael G; McCurdy, Michael T; Reed, Robert M

2014-01-01

16

[Acute hepatic vascular complications].  

PubMed

Acute hepatic vascular complications are rare. Acute portal vein thrombosis (PVT) and the Budd-Chiari syndrome (BSC) are the leading causes. Coagulopathy and local factors are present in up to 80% of cases. Diagnosis is established by colour-coded Doppler sonography, contrast-enhanced computed tomography or magnetic resonance imaging. Patients with acute PVT present with abdominal pain and disturbed intestinal motility. In the absence of cirrhosis anticoagulation with heparin is established followed by oral anticoagulation. In severe cases, surgical thrombectomy or transjugular thrombolysis with stent shunt may be necessary. Acute or fulminant BCS may require emergency liver transplantation or a transjugular intrahepatic portosystemic stent shunt, if patients present with acute liver failure. Milder cases receive anticoagulation for thrombolysis of occluded hepatic veins. Sinusoidal obstruction syndrome (SOS) is diagnosed after total body irradiation or chemotherapy, the term SOS replacing the former veno-occlusive disease. The treatment of congenital vascular malformations, complications in the setting of OLTX as well as patients with hepatic involvement of hereditary hemorrhagic telangiectasia requires significant expertise in a multidisciplinary approach. PMID:21667100

Ochs, A

2011-07-01

17

Optimal management of alcoholic hepatitis.  

PubMed

Alcoholic hepatitis, a clinical syndrome among people with chronic and active alcohol abuse presents with with jaundice and liver failure with or without hepatic encephalopathy. In patients with severe episode, this condition has a potential for 40-50% mortality within a month of presentation. Corticosteroids and pentoxifylline, only available current treatment options provide only about 50% survival benefit. Response to corticosteroids can only be assessed at 1 week of initiation of these drugs using Lille score or documentation of improvement in bilirubin levels. Requirement of minimum 6 months abstinence for liver transplantation cannot be met for alcoholic hepatitis patients who fail to respond to steroids. Emerging data on the benefit of liver transplantation for select patients with first episode of severe AH with non-response to steroids are encouraging. There remains an unmet need for studies assessing newer therapeutic targets and drugs and for optimizing the currently available treatment options. In this regard, decision to promote clinical and translational research by the National Institute of Alcohol Abuse and Alcoholism will be helpful in improving survival of patients with alcoholic hepatitis. PMID:24632766

Raff, E; Singal, A K

2014-03-01

18

Alcoholic hepatitis and concomitant hepatitis C virus infection  

PubMed Central

Hepatitis C virus (HCV) infection and alcohol abuse are two most important causes of chronic liver disease in the United States. Alcoholic hepatitis is a unique clinical syndrome among patients with chronic and active alcohol abuse with a potential for high short-term mortality. About 20% of patients presenting with alcoholic hepatitis have concomitant HCV infection. Mortality from alcoholic hepatitis is increased in the presence of concomitant hepatitis C due to synergistic interaction between HCV and alcohol in causing hepatocellular damage. Large prospective randomized studies are needed to develop guidelines on the use of corticosteroids among patients with alcoholic hepatitis and concomitant HCV infection. The impact of antiviral therapy on mortality and outcome in the setting of alcoholic hepatitis remains a novel area for future research. PMID:25232227

Shoreibah, Mohamed; Anand, Bhupinderjit S; Singal, Ashwani K

2014-01-01

19

Acute hepatic failure in children.  

PubMed Central

Many diseases may present as acute hepatic failure in the pediatric age group, including viral hepatitis A and B, adverse drug reactions, both toxic and "hepatitic," and inherited metabolic disorders such as tyrosinemia, alpha 1 antitrypsin deficiency, and Wilson's disease. Management is primarily supportive, with care taken to anticipate the known complications of hepatic failure. Few "curative" therapies are known, although attempts at stimulating hepatic regeneration may be helpful. Images FIG. 1 FIG. 3 FIG. 4 PMID:6433587

Riely, C. A.

1984-01-01

20

Alcoholic hepatitis: a comprehensive review of pathogenesis and treatment.  

PubMed

Alcoholic hepatitis (AH) is an acute hepatic inflammation associated with significant morbidity and mortality. Current evidence suggests that the pathogenesis is the end result of the complex interplay between ethanol metabolism, inflammation and innate immunity. Several clinical scoring systems have been derived to predict the clinical outcomes of patients with AH; such as Child-Turcotte-Pugh score, the Maddrey discriminant function, the Lille Model, the model for end stage liver disease scores, and the Glasgow alcoholic hepatitis score. At present, Corticosteroids or pentoxifylline are the current pharmacologic treatment options; though the outcomes from the therapies are poor. Liver transplantation as the treatment of alcoholic hepatitis remains controversial, and in an era of organ shortage current guidelines do not recommend transplantation as the treatment option. Because of the limitations in the therapeutic options, it is no doubt that there is a critical need for the newer and more effective pharmacological agents to treat AH. PMID:24876748

Chayanupatkul, Maneerat; Liangpunsakul, Suthat

2014-05-28

21

Alcoholic Hepatitis: Steroids vs. Pentoxifylline  

PubMed Central

Alcoholic hepatitis (AH) remains a major cause of liver-related morbidity and mortality in the United States and is actually increasing in certain areas of Europe. Thus, there is a pressing need for new therapies/approaches. Major barriers for reducing morbidity, mortality, and costs of care include: lack of translational animal and human studies of new therapies for AH; limited trials of combination therapies in AH targeted at specific disease mechanisms (e.g., gut permeability, cytokines, oxidative stress); limited studies on non-invasive, non-mortality end points; few studies on mechanisms of steroid non-responsiveness; and inadequate prognostic indicators, to name only a few. In spite of these gaps, we have made major advances in understanding mechanisms for AH and appropriate therapies for AH. This article reviews mechanisms and rationale for use of steroids and pentoxifylline in AH and future directions in therapy. PMID:23750115

Smart, Laura; Gobejishvili, Leila; Crittenden, Neil; Barve, Shirish; McClain, Craig J.

2013-01-01

22

Alcoholic hepatitis: current challenges and future directions.  

PubMed

Alcoholic hepatitis is a distinct clinical syndrome among people with chronic and active alcohol abuse, with a potential for 30%-40% mortality at 1 month among those with severe disease. Corticosteroids or pentoxifylline are the current pharmacologic treatment options, but they provide only about 50% survival benefit. These agents are recommended for patients with modified discriminant function (mDF) ? 32 or Model for End-Stage Liver Disease score ? 18. The Lille score is used to determine response to steroids. Currently, a minimum of 6 months of 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 nonresponsive 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 pharmacologic treatment options for patients with alcoholic hepatitis that are being pursued through upcoming consortium studies. PMID:23811249

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

2014-04-01

23

[Diagnostic and therapeutic strategies for severe alcoholic hepatitis].  

PubMed

Alcoholic hepatitis (AH) is defined as an acute hepatic manifestation resulting from heavy alcohol intake. Histologically, alcoholic steatohepatitis (ASH) is characterized by hepatocellular steatosis, inflammation, and fibrosis. Alcohol abstinence is the sine qua non of therapy for AH and, in the milder forms, is prerequisite to clinical recovery. Severe ASH may lead to multi-organ failure such as acute kidney injury and infection, which has a major impact on survival and thus should be closely monitored. Patients with severe ASH have a drastic short-term mortality of up to 40-50%. Specific therapies should be considered for patients with severe ASH at risk of early death. Corticosteroids are the standard of care for patients with severe ASH. When corticosteroids are contraindicated, pentoxifylline may be an alternative option. Steroid responsiveness should be evaluated on the basis of Lille score. Tactically, we should explore novel therapeutic targets to suppress inflammation based on cytokine profiles, promote hepatic regeneration, limit innate immune responses, and restore altered gut mucosal integrity in severe ASH. (Korean J Gastroenterol 2015;65:4-11). PMID:25603848

Kim, Won

2015-01-25

24

Severe alcoholic hepatitis-current concepts, diagnosis and treatment options  

PubMed Central

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

Kim, Won; Kim, Dong Joon

2014-01-01

25

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

PubMed

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

Kim, Won; Kim, Dong Joon

2014-10-27

26

Acute hepatitis E complicated by acute pancreatitis and multiorgan dysfunction.  

PubMed

We report this rare case of a 27-year-old man who presented with acute hepatitis E and went on to develop acute epigastric pain. He was diagnosed to have acute severe pancreatitis with shock and acute renal failure due to hepatitis E. Such a phenomenon has rarely been reported in the literature, with patients following a benign course and complete recovery after conservative management and analgesia. Awareness of this potentially life-threatening complication, especially in young men from endemic areas with acute hepatitis E presenting with abdomen pain has been highlighted. PMID:24899005

Karanth, Suman S; Khan, Zohaib; Rau, Nileshwar Radhakrishna; Rao, Karthik

2014-01-01

27

Zafirlukast-induced acute hepatitis.  

PubMed

Zafirlukast, a competitive cysteinyl leukotriene receptor antagonist, is a new class of asthma medications. It has shown an adverse event profile similar to that of placebo. Herein, we present a 69-year-old female patient who suffered from general malaise, poor appetite, nausea and jaundice after 3 months of zafirlukast therapy for asthma. She had no past history of liver disease, nor history of alcoholism, herb medication, blood transfusion, acupuncture, tattoo or recent traveling history. Liver biochemistries revealed elevated serum alanine aminotransferase and aspartase aminotransferase levels up to 481 U/L and 212 U/L, respectively. Moreover, peak serum total bilirubin level was elevated to 34.8 mg/dL during admission. Serum viral hepatitis marker, antinuclear antibody, anti-mitochondrial antibody and anti-smooth muscle antibody were all negative. Her general condition and liver biochemistries improved gradually after zafirlukast was discontinued. Roussel Uclaf causality assessment for adverse drug reaction confirmed the diagnosis of drug-induced liver injury. This case reminds us that zafirlukast is a potentially hepato-toxic drug. If clinical manifestations of hepatitis develop, patients should be managed cautiously and closely monitored for liver biochemistries. If drug-induced hepatitis is suspected, medication should be discontinued immediately to prevent further liver injury. PMID:12583521

Su, Chien-Wei; Wu, Jaw-Ching; Huang, Yi-Hsiang; Huang, Yi-Shin; Chang, Full-Young; Lee, Shou-Dong

2002-11-01

28

Acute esophageal necrosis caused by alcohol abuse  

PubMed Central

Acute esophageal necrosis (AEN) is extremely rare and the pathogenesis of this is still unknown. We report a case of AEN caused by alcohol abuse. In our case, the main pathogenesis could be accounted for low systemic perfusion caused by severe alcoholic lactic acidosis. After the healing of AEN, balloon dilatation was effective to manage the stricture. PMID:16222758

Endo, Tetsu; Sakamoto, Juichi; Sato, Ken; Takimoto, Miyako; Shimaya, Koji; Mikami, Tatsuya; Munakata, Akihiro; Shimoyama, Tadashi; Fukuda, Shinsaku

2005-01-01

29

Animal models of acute hepatic failure  

PubMed Central

The understanding and treatment of acute hepatic failure has developed rapidly over the last 40 years reducing morbidity and mortality from this syndrome. Progress has been made by the study of animal models that reflect the clinical, biochemical and histological pattern of the syndrome seen in man. This is of increasing importance with the use of therapeutic intervention, liver transplantation and the use of extra-corporeal liver support devices. This review examines and critically appraises the various approaches to the study of acute hepatic failure in animal models, including both surgical and pharmacological approaches. PMID:10762442

Rahman, Tony Manibur; Hodgson, Humphrey J F

2000-01-01

30

Role of Fn14 in acute alcoholic steatohepatitis in mice.  

PubMed

TNF-like weak inducer of apoptosis (TWEAK) is a growth factor for bipotent liver progenitors that express its receptor, fibroblast growth factor-inducible 14 (Fn14), a TNF receptor superfamily member. Accumulation of Fn14(+) progenitors occurs in severe acute alcoholic steatohepatitis (ASH) and correlates with acute mortality. In patients with severe ASH, inhibition of TNF-? increases acute mortality. The aim of this study was to determine whether deletion of Fn14 improves the outcome of liver injury in alcohol-consuming mice. Wild-type (WT) and Fn14 knockout (KO) mice were fed control high-fat Lieber deCarli diet or high-fat Lieber deCarli diet with 2% alcohol (ETOH) and injected intraperitoneally with CCl4 for 2 wk to induce liver injury. Mice were euthanized 3 or 10 days after CCl4 treatment. Survival was assessed. Liver tissues were analyzed for cell death, inflammation, proliferation, progenitor accumulation, and fibrosis by quantitative RT-PCR, immunoblot, hydroxyproline content, and quantitative immunohistochemistry. During liver injury, Fn14 expression, apoptosis, inflammation, hepatocyte replication, progenitor and myofibroblast accumulation, and fibrosis increased in WT mice fed either diet. Mice fed either diet expressed similar TWEAK/Fn14 levels, but ETOH-fed mice had higher TNF-? expression. The ETOH-fed group developed more apoptosis, inflammation, fibrosis, and regenerative responses. Fn14 deletion did not reduce hepatic TNF-? expression but improved all injury parameters in mice fed the control diet. In ETOH-fed mice, Fn14 deletion inhibited TNF-? induction and increased acute mortality, despite improvement in liver injury. Fn14 mediates wound-healing responses that are necessary to survive acute liver injury during alcohol exposure. PMID:25524063

Karaca, Gamze; Xie, Guanhua; Moylan, Cynthia; Swiderska-Syn, Marzena; Guy, Cynthia D; Krüger, Leandi; Machado, Mariana Verdelho; Choi, Steve S; Michelotti, Gregory A; Burkly, Linda C; Diehl, Anna Mae

2015-02-15

31

Osteopontin is an important mediator of alcoholic liver disease via hepatic stellate cell activation  

PubMed Central

AIM: To investigate over-expression of Osteopontin (OPN) pathway expression and mechanisms of action in human alcoholic liver disease (ALD), in vivo and in vitro acute alcohol models. METHODS: OPN pathway was evaluated in livers from patients with progressive stages of human ALD and serum from drinkers with and without liver cirrhosis. In vitro stellate LX2 cells exposed to acute alcohol and in vivo in acute alcoholic steatosis mouse models were also investigated for OPN pathway expression and function. WT and OPN-/- mice were administered an acute dose of alcohol and extent of liver injury was examined by histopathology and liver biochemistry after 16-24 h. The causative role of OPN was studied in OPN knockout animals and in vitro in stellate LX2 cells, utilizing siRNA, aptamer and neutralizing antibodies to block OPN and OPN pathway. OPN pathway expression and downstream functional consequences were measured for signaling by Western blotting, plasmin activation by spectrophotometric assays and cell migration by confocal imaging and quantitation. RESULTS: OPN expression positively correlated with disease severity in patients with progressive stages of ALD. In vivo, associated with alcoholic steatosis, a single dose of acute alcohol significantly increased hepatic OPN mRNA and protein, and a cleaved OPN form in a dose dependent manner. OPN mRNA and secreted OPN also increased in parallel with activation of LX2 stellate cells within 4 h of a single dose of alcohol. Expression of OPN receptors, ?v?3-integrin and CD44, increased in human ALD, and in vivo and in vitro with alcohol administration. This was accompanied by downstream phosphorylation of Akt and Erk, increased mRNA expression of several fibrogenesis, fibrinolysis and extracellular matrix pathway genes, plasmin activation and hepatic stellate cell (HSC) migration. Inhibition of OPN and OPN-receptor mediated signaling partially inhibited alcohol-induced HSC activation, plasmin activity and cell migration. CONCLUSION: OPN is a key mediator of the alcohol-induced effects on hepatic stellate cell functions and liver fibrogenesis. PMID:25278703

Seth, Devanshi; Duly, Alastair; Kuo, Paul C; McCaughan, Geoffrey W; Haber, Paul S

2014-01-01

32

An outbreak of refrigerant-induced acute hepatitis in Hong Kong.  

PubMed

We report a cluster of acute hepatitis in five air-conditioning maintenance workers following accidental exposure to 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123). They presented to us with complaints of feverishness, generalised malaise, and epigastric discomfort. Their blood biochemistry tests were compatible with acute hepatitis. Viral hepatitis serology, tests for autoimmune hepatitis, and analyses for drugs and alcohol consumption were all negative. No focal hepatic lesion was detected by ultrasound imaging. Percutaneous liver biopsy samples were taken from two of them. The patients were managed with supportive treatment. All had spontaneous, but slow, recovery. Their liver function tests returned to normal after 4 months and their outcomes were favourable. Physicians should be aware of this occupational disease entity. PMID:25488036

Kan, Y M; Lau, C F; Chan, W C; Chan, W S; Tung, Y M; Loo, C K

2014-12-01

33

Contribution of hepatitis E virus in acute sporadic hepatitis in north western India  

PubMed Central

Background & objectives: Hepatitis E virus (HEV) causes acute viral hepatitis. Majority of the documented studies on hepatitis E have been focused on the incidence of this disease in northern and south central India. Limited data are available on HEV infection among acute sporadic hepatitis cases in north western India. The present study was undertaken to investigate the contribution of hepatitis E virus infection in sporadic hepatitis cases in Rajasthan and neighbouring States. Methods: Seven hundred and thirty six patients suspected to have viral hepatitis were screened for the hepatotropic viral markers, hepatitis A, B, C and E by using commercial enzyme immunoassay kits with a high sensitivity and specificity. The acute nature of HEV infection was also confirmed by the detection of HEV RNA by nested RT-PCR. Results: Hepatitis E was found to be the major cause of acute sporadic viral hepatitis (49.7%) in this region of India. Mixed infections of HEV-HAV (1.2%), HEV-HBV (6.1%), and HEV-HCV (1.7%) were also detected. No viral marker was detected in 32 per cent cases. Interpretation & conclusion: HEV was found as the major aetiological agent of acute sporadic viral hepatitis in Rajasthan (north western India). It is important to screen primarily for all the common enterically and parenterally transmitted hepatotropic viral markers in acute sporadic viral hepatitis. There is a need to do additional serological and molecular tests to identify the aetiological agent in the cases of acute hepatitis. PMID:23041743

Chandra, Nidhi Subhash; Sharma, Asha; Rai, Ramesh Roop; Malhotra, Bharti

2012-01-01

34

Acute hepatitis associated with autochthonous hepatitis E virus infection--San Antonio, Texas, 2009.  

PubMed

Locally acquired hepatitis E infection is increasingly being observed in industrialized countries. We report 2 cases of autochthonous acute hepatitis E in the United States. Hepatitis E virus genotype 3a related to US-2 and swine hepatitis E virus strains was isolated from one of the patients, indicating potential food-borne or zoonotic transmission. PMID:21896699

Tohme, Rania A; Drobeniuc, Jan; Sanchez, Roger; Heseltine, Gary; Alsip, Bryan; Kamili, Saleem; Hu, Dale J; Guerra, Fernando; Teshale, Eyasu H

2011-10-01

35

In vitro and in vivo models of acute alcohol exposure  

PubMed Central

Alcohol abuse is a global problem due to the financial burden on society and the healthcare system. While the harmful health effects of chronic alcohol abuse are well established, more recent data suggest that acute alcohol consumption also affects human wellbeing. Thus, there is a need for research models in order to fully understand the effect of acute alcohol abuse on different body systems and organs. The present manuscript summarizes the interdisciplinary advantages and disadvantages of currently available human and non-human models of acute alcohol abuse, and identifies their suitability for biomedical research. PMID:19291816

Dolganiuc, Angela; Szabo, Gyongyi

2009-01-01

36

Alcohol use disorders and acute alcohol use preceding suicide in China  

PubMed Central

Objectives Identify distinguishing characteristics of subgroups of suicides classified according to different patterns of alcohol use prior to death. Methods Three groups of suicide decedents from a representative sample of 454 male suicides in China identified in a national psychological autopsy study were classified and compared: decedents with an alcohol use disorder during the year prior to death, those without an alcohol use disorder who used alcohol acutely at the time of suicide, and those with neither an alcohol use disorder nor acute use. Results Compared with suicides unrelated to alcohol, those with an alcohol use disorder were more likely to have made previous suicide attempts (adjusted OR, 95%CI=1.94, 1.07–3.53), and suicides with acute alcohol use were less likely to have poor overall functioning in the month before death (0.36, 0.20–0.63). Conclusions The characteristics of male suicide decedents with an alcohol use disorder, using alcohol acutely but without an alcohol use disorder, and with no alcohol involvement are somewhat different, suggesting the potential value of tailored prevention strategies. PMID:19850415

Zhang, Yali; Conner, Kenneth R.; Phillips, Michael R.

2009-01-01

37

Hepatic stellate cells and innate immunity in alcoholic liver disease  

PubMed Central

Constant alcohol consumption is a major cause of chronic liver disease, and there has been a growing concern regarding the increased mortality rates worldwide. Alcoholic liver diseases (ALDs) range from mild to more severe conditions, such as steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The liver is enriched with innate immune cells (e.g. natural killer cells and Kupffer cells) and hepatic stellate cells (HSCs), and interestingly, emerging evidence suggests that innate immunity contributes to the development of ALDs (e.g. steatohepatitis and liver fibrosis). Indeed, HSCs play a crucial role in alcoholic steatosis via production of endocannabinoid and retinol metabolites. This review describes the roles of the innate immunity and HSCs in the pathogenesis of ALDs, and suggests therapeutic targets and strategies to assist in the reduction of ALD. PMID:21633659

Suh, Yang-Gun; Jeong, Won-Il

2011-01-01

38

Hepatitis C, Acute Humoral Rejection, and Renal Allograft Survival  

Microsoft Academic Search

The effect of recipient hepatitis C virus (HCV) in- fection on renal allograft loss and acute rejection in kidney transplantation remains controversial. We studied 354 renal allograft recipients transplanted during 1996 to 2001 who had HCV antibodies (Ab) measured before transplantation. The primary outcome was death-censored allograft loss and the secondary outcome was acute humoral rejection (AHR). Com- pared with

JOHN P. FORMAN; NINA TOLKOFF-RUBIN; MANUEL PASCUAL; JULIE LIN

2004-01-01

39

Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure.  

PubMed

Hepatic encephalopathy in a hospitalized cirrhotic patient is associated with a high mortality rate and its presence adds further to the mortality of patients with acute-on-chronic liver failure (ACLF). The exact pathophysiological mechanisms of HE in this group of patients are unclear but hyperammonemia, systemic inflammation (including sepsis, bacterial translocation, and insulin resistance) and oxidative stress, modulated by glutaminase gene alteration, remain as key factors. Moreover, alcohol misuse, hyponatremia, renal insufficiency, and microbiota are actively explored. HE diagnosis requires exclusion of other causes of neurological, metabolic and psychiatric dysfunction. Hospitalization in the ICU should be considered in every patient with overt HE, but particularly if this is associated with ACLF. Precipitating factors should be identified and treated as required. Evidence-based specific management options are limited to bowel cleansing and non-absorbable antibiotics. Ammonia lowering drugs, such as glycerol phenylbutyrate and ornithine phenylacetate show promise but are still in clinical trials. Albumin dialysis may be useful in refractory cases. Antibiotics, prebiotics, and treatment of diabetes reduce systemic inflammation. Where possible and not contraindicated, large portal-systemic shunts may be embolized but liver transplantation is the most definitive step in the management of HE in this setting. HE in patients with ACLF appears to be clinically and pathophysiologically distinct from that of acute decompensation and requires further studies and characterization. PMID:25218789

Romero-Gómez, Manuel; Montagnese, Sara; Jalan, Rajiv

2014-09-10

40

[Acute paraparesis in chronic hepatic disease].  

PubMed

An acuta caude equina syndrome following portacaval shunt in a 64-year-old patient suffering from liver cirrhosis is reported. Diagnosis of a hepatic radiculopathy was confirmed by clinical and electrophysiological findings. A nearly complete remission of the neurological symptoms was achieved by treatment of the primary liver disease. Since there are only a few descriptions of severe hepatic polyneuro- and radiculopathies, the differential diagnosis of hepatic myelopathy is discussed. PMID:1851969

Jeske, J; Schädlich, H J; Sandmann, J; Karbe, H; Haupt, W F; Karenberg, A

1991-02-01

41

Pharmacokinetics of Diclofenac Sodium in Chronic Active Hepatitis and Alcoholic Cirrhosis  

Microsoft Academic Search

The objective of this study was to assess the pharmacokinetics of diclofenac sodium and its five metabolites following administration of a 150 mg oral dose to healthy subjects and patients with either chronic active hepatitis of varying morphology or alcoholic cirrhosis. Six healthy subjects, 6 chronic active hepatitis patients, and 6 alcoholic cirrhosis patients were enrolled in this prospective, open-label,

Jennifer S. Lill; Teresa OSullivan; Larry A. Bauer; John R. Horn; Robert Carithers; D. Eugene Strandness; Henry Lau; Keith Chan; Kamlesh Thakker

2000-01-01

42

Nitric oxide and pro-inflammatory cytokines in acute hepatitis B  

Microsoft Academic Search

Background: Experimental studies demonstrate that hepatitis B virus may induce nitric oxide (NO) production in infected hepatocytes. Its presence in acute hepatitis B patients has not been studied. Methods: Serum levels of nitric oxide and its regulatory pro-inflammatory cytokines were detected in 15 patients with uncomplicated acute hepatitis B, 19 blood donors and 15 chronic hepatitis B patients. Cytokines were

Meri Koulentaki; George Notas; Efthimia Petinaki; Vassilis Valatas; Ioannis A Mouzas; Elias Castanas; Elias A Kouroumalis

2004-01-01

43

The acute hepatic porphyrias: current status and future challenges.  

PubMed

The porphyrias are predominantly inherited metabolic disorders, which result from a specific deficiency of one of the eight enzymes along the pathway of haem biosynthesis. Historically, they have been classified into hepatic and erythropoietic forms, based on the primary site of expression of the prevailing dysfunctional enzyme. From a clinical point of view, however, it is more convenient to subdivide them into acute and non-acute porphyrias, thereby primarily considering the potential occurrence of life-threatening acute neurovisceral attacks. Unrecognised or untreated, such an acute porphyric attack is associated with a significant mortality of up to 10%. The acute hepatic porphyrias comprise acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and ?-aminolevulinic acid dehydratase deficiency porphyria. Making a precise diagnosis may be difficult because the different types of porphyrias may show overlapping clinical and biochemical characteristics. To date, the therapeutic possibilities are limited and mainly symptomatic. In this overview we report on what is currently known about pathogenesis, clinic, diagnostics, and therapy of the acute hepatic porphyrias. We further point out actual and future challenges in the management of these diseases. PMID:20955962

Siegesmund, Marko; van Tuyll van Serooskerken, Anne-Moniek; Poblete-Gutiérrez, Pamela; Frank, Jorge

2010-10-01

44

Acute pancreatitis associated with acute viral hepatitis A (HAV) - a case report.  

PubMed

In this case report, a young woman had acute viral hepatitis (HAV) and acute pancreatitis together. She was admitted to our hospital with fever, jaundice and abdominal pain. Hepatic and pancreatic enzymes were elevated. Her serum alanine aminotransferase (ALT) level was high. An initial abdominal ultrasound was per-formed at hospital and revealed features of acute viral hepatitis. Spiral computed imaging revealed imaging features of an acute stage of pancreatitis and gallbladder wall thickness. HAV infection was diagnosed by the detection of immunoglobulin M (IgM) against HAV in the serum. She was closely monitored and treated conservatively. On 10th day of hospital admission she was discharge after an uneventful recovery. In the current literature HAV infections have rarely been reported as a cause of acute pancreatitis. PMID:23416831

Arafat, S M; Azad, A K; Basher, A; Ananna, M A; Islam, M S; Abdullah, S; Abdullah, A M; Islam, M A

2013-01-01

45

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

PubMed Central

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

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

2014-01-01

46

Molecular mechanisms of hepatic fibrosis in non-alcoholic steatohepatitis.  

PubMed

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 other causes of liver damage. Fibrosis due to NASH develops primarily in the pericentral areas, surrounding groups of hepatocytes and thickening the space of Disse. This pericellular fibrosis eventually forms septa isolating regenerating nodules. The main cell type responsible for extracellular matrix deposition is represented by hepatic stellate cells that undergo activation in conditions of liver injury enabling them to participate in the liver wound healing process. Although the profibrogenic mechanisms operating in NASH are partly in common with those observed in other chronic liver diseases, the altered pattern of circulating adipokines, oxidative stress generation and the hormonal profile associated with the metabolic syndrome might have a specific role for the induction of fibrogenesis in this condition. In this paper, we review recent developments regarding the basic mechanisms of NASH and the involvement of hepatic stellate cells in this disease. PMID:20460917

Rombouts, Krista; Marra, Fabio

2010-01-01

47

Alcohol induced hepatic degeneration in a hepatitis C virus core protein transgenic mouse model.  

PubMed

Hepatitis C virus (HCV) has become a major public health issue. It is prevalent in most countries. HCV infection frequently begins without clinical symptoms, before progressing to persistent viremia, chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) in the majority of patients (70% to 80%). Alcohol is an independent cofactor that accelerates the development of HCC in chronic hepatitis C patients. The purpose of the current study was to evaluate ethanol-induced hepatic changes in HCV core-Tg mice and mutant core Tg mice. Wild type (NTG), core wild-Tg mice (TG-K), mutant core 116-Tg mice (TG-116) and mutant core 99-Tg mice (TG-99) were used in this investigation. All groups were given drinking water with 10% ethanol and 5% sucrose for 13 weeks. To observe liver morphological changes, we performed histopathological and immunohistochemical examinations. Histopathologically, NTG, TG-K and TG-116 mice showed moderate centrilobular necrosis, while severe centrilobular necrosis and hepatocyte dissociation were observed in TG-99 mice with increasing lymphocyte infiltration and piecemeal necrosis. In all groups, a small amount of collagen fiber was found, principally in portal areas. None of the mice were found to have myofibroblasts based on immunohistochemical staining specific for ?-SMA. CYP2E1-positive cells were clearly detected in the centrilobular area in all groups. In the TG-99 mice, we also observed cells positive for CK8/18, TGF-?1 and phosphorylated (p)-Smad2/3 and p21 around the necrotic hepatocytes in the centrilobular area (p < 0.01). Based on our data, alcohol intake induced piecemeal necrosis and hepatocyte dissociation in the TG-99 mice. These phenomena involved activation of the TGF-?1/p-Smad2/3/p21 signaling pathway in hepatocytes. Data from this study will be useful for elucidating the association between alcohol intake and HCV infection. PMID:24608925

Noh, Dong-Hyung; Lee, Eun-Joo; Kim, Ah-Young; Lee, Eun-Mi; Min, Chang-Woo; Kang, Kyung-Ku; Lee, Myeong-Mi; Kim, Sang-Hyeob; Sung, Soo-Eun; Hwang, Meeyul; Yu, Dae-Yeul; Jeong, Kyu-Shik

2014-01-01

48

Differences in Acute Alcohol-Induced Behavioral Responses Among Zebrafish Populations  

E-print Network

as CNS dis- orders may be modeled and studied with this species. Alcoholism and alcohol abuse are among: Alcoholism, Alcohol Abuse, Acute Alcohol Administration, Strain Comparison, Zebrafish, Zebra DanioOH or ethyl alcohol) abuse cost more than $150 billion yearly and resulted in 40,000 deaths in the United

Kalueff, Allan V.

49

Altered hepatic retinyl ester concentration and acyl composition in response to alcohol consumption.  

PubMed

Retinoids (vitamin A and its metabolites) are essential micronutrients that regulate many cellular processes. Greater than 70% of the body's retinoid reserves are stored in the liver as retinyl ester (RE). Chronic alcohol consumption induces depletion of hepatic retinoid stores, and the extent of this has been correlated with advancing stages of alcoholic liver disease. The goal of this study was to analyze the mechanisms responsible for depletion of hepatic RE stores by alcohol consumption A change in the fatty-acyl composition of RE in alcohol-fed mice was observed within two weeks after the start of alcohol consumption. Specifically, alcohol-feeding was associated with a significant decline in hepatic retinyl palmitate levels; however, total RE levels were maintained by a compensatory increase in levels of usually minor RE species, particularly retinyl oleate. Our data suggests that alcohol feeding initially stimulates a futile cycle of RE hydrolysis and synthesis, and that the change in RE acyl composition is associated with a change in the acyl composition of hepatic phosphatidylcholine. The alcohol-induced change in RE acyl composition was specific to the liver, and was not seen in lung or white adipose tissue. This shift in hepatic RE fatty acyl composition is a sensitive indicator of alcohol consumption and may be an early biomarker for events associated with the development of alcoholic liver disease. PMID:24046868

Clugston, Robin D; Jiang, Hongfeng; Lee, Man Xia; Berk, Paul D; Goldberg, Ira J; Huang, Li-Shin; Blaner, William S

2013-07-01

50

Altered hepatic retinyl ester concentration and acyl composition in response to alcohol consumption.  

PubMed

Retinoids (vitamin A and its metabolites) are essential micronutrients that regulate many cellular processes. Greater than 70% of the body's retinoid reserves are stored in the liver as retinyl ester (RE). Chronic alcohol consumption induces depletion of hepatic retinoid stores, and the extent of this has been correlated with advancing stages of alcoholic liver disease. The goal of this study was to analyze the mechanisms responsible for depletion of hepatic RE stores by alcohol consumption. A change in the fatty-acyl composition of RE in alcohol-fed mice was observed within two weeks after the start of alcohol consumption. Specifically, alcohol-feeding was associated with a significant decline in hepatic retinyl palmitate levels; however, total RE levels were maintained by a compensatory increase in levels of usually minor RE species, particularly retinyl oleate. Our data suggests that alcohol feeding initially stimulates a futile cycle of RE hydrolysis and synthesis, and that the change in RE acyl composition is associated with a change in the acyl composition of hepatic phosphatidylcholine. The alcohol-induced change in RE acyl composition was specific to the liver, and was not seen in lung or white adipose tissue. This shift in hepatic RE fatty acyl composition is a sensitive indicator of alcohol consumption and may be an early biomarker for events associated with the development of alcoholic liver disease. PMID:23583843

Clugston, Robin D; Jiang, Hongfeng; Lee, Man Xia; Berk, Paul D; Goldberg, Ira J; Huang, Li-Shin; Blaner, William S

2012-07-01

51

Granulocytapheresis for the treatment of severe alcoholic hepatitis: a case series and literature review.  

PubMed

Severe alcoholic hepatitis has a high mortality rate due to limited therapeutic methods. Although corticosteroids have been used to control the inflammatory response, the outcomes vary and no standardized therapy has been established. Novel therapeutic approaches, such as anti-TNF-?, pentoxifilline, and others have been tested clinically on the basis of their cytokinemic pathophysiology with limited success. However, treatment of leukocytosis that causes cytokinemia and hepatic inflammation in patients via granulocytapheresis and leukocytapheresis showed promising results in a number of reports. Here, we report two cases of severe alcoholic hepatitis treated with granulocytapheresis. The liver function and inflammation recovered after the therapy. A review of 35 cases treated with granulocytapheresis and leukocytapheresis demonstrated their efficacy in treating alcoholic hepatitis by controlling leukocytosis as well as cytokines such as IL-8. Multidisciplinary treatment for severe alcoholic hepatitis should be considered case by case on the basis of the complexity and severity of the condition. PMID:24052196

Kamimura, Kenya; Imai, Michitaka; Sakamaki, Akira; Mori, Shigeki; Kobayashi, Masaaki; Mizuno, Ken-Ichi; Takeuchi, Manabu; Suda, Takeshi; Nomoto, Minoru; Aoyagi, Yutaka

2014-02-01

52

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

PubMed

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

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

53

Porphyria cutanea tarda, hepatitis C, alcoholism, and hemochromatosis: a case report and review of the literature.  

PubMed

Porphyria cutanea tarda (PCT) is associated with estrogen, certain medications, alcohol abuse, hepatitis viruses, and iron overload. Numerous studies have demonstrated an increased incidence of hepatitis C in patients with PCT; therefore, hepatitis screening should be routinely performed on these patients. On the other hand, although studies have long suspected hereditary hemochromatosis (HH) to be an underlying condition of PCT, many physicians have a low index of suspicion. Also, diagnosis of HH has been difficult until recently, when the gene mutation was identified. We present a case of a patient with PCT, hepatitis C, and alcoholism who was homozygous for the HH gene mutation. PMID:15074347

Sams, Hunter; Kiripolsky, Monika G; Bhat, Leena; Stricklin, George P

2004-03-01

54

Efficacy of metadoxine in the management of acute alcohol intoxication.  

PubMed

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

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

2002-01-01

55

Maltol, a food flavoring agent, attenuates acute alcohol-induced oxidative damage in mice.  

PubMed

The purpose of this study was to evaluate the hepatoprotective effect of maltol, a food-flavoring agent, on alcohol-induced acute oxidative damage in mice. Maltol used in this study was isolated from red ginseng (Panax ginseng C.A Meyer) and analyzed by high performance liquid chromatography (HPLC) and mass spectrometry. For hepatoprotective activity in vivo, pretreatment with maltol (12.5, 25 and 50 mg/kg; 15 days) drastically prevented the elevated activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and triglyceride (TG) in serum and the levels of malondialdehyde (MDA), tumor necrosis factor-? (TNF-?), interleukin-1? (IL-1?) in liver tissue (p < 0.05). Meanwhile, the levels of hepatic antioxidant, such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were elevated by maltol pretreatment, compared to the alcohol group (p < 0.05). Histopathological examination revealed that maltol pretreatment significantly inhibited alcohol-induced hepatocyte apoptosis and fatty degeneration. Interestingly, pretreatment of maltol effectively relieved alcohol-induced oxidative damage in a dose-dependent manner. Maltol appeared to possess promising anti-oxidative and anti-inflammatory capacities. It was suggested that the hepatoprotective effect exhibited by maltol on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties. PMID:25608939

Han, Ye; Xu, Qi; Hu, Jiang-Ning; Han, Xin-Yue; Li, Wei; Zhao, Li-Chun

2015-01-01

56

Maltol, a Food Flavoring Agent, Attenuates Acute Alcohol-Induced Oxidative Damage in Mice  

PubMed Central

The purpose of this study was to evaluate the hepatoprotective effect of maltol, a food-flavoring agent, on alcohol-induced acute oxidative damage in mice. Maltol used in this study was isolated from red ginseng (Panax ginseng C.A Meyer) and analyzed by high performance liquid chromatography (HPLC) and mass spectrometry. For hepatoprotective activity in vivo, pretreatment with maltol (12.5, 25 and 50 mg/kg; 15 days) drastically prevented the elevated activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and triglyceride (TG) in serum and the levels of malondialdehyde (MDA), tumor necrosis factor-? (TNF-?), interleukin-1? (IL-1?) in liver tissue (p < 0.05). Meanwhile, the levels of hepatic antioxidant, such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were elevated by maltol pretreatment, compared to the alcohol group (p < 0.05). Histopathological examination revealed that maltol pretreatment significantly inhibited alcohol-induced hepatocyte apoptosis and fatty degeneration. Interestingly, pretreatment of maltol effectively relieved alcohol-induced oxidative damage in a dose-dependent manner. Maltol appeared to possess promising anti-oxidative and anti-inflammatory capacities. It was suggested that the hepatoprotective effect exhibited by maltol on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties. PMID:25608939

Han, Ye; Xu, Qi; Hu, Jiang-ning; Han, Xin-yue; Li, Wei; Zhao, Li-chun

2015-01-01

57

Importance of markers of hepatitis B virus in alcoholic liver disease.  

PubMed Central

To determine the importance of the presence of serological markers of hepatitis B virus infection in patients with alcohol related liver disease we compared cumulative alcohol intake and clinical and histological features in patients with markers of hepatitis B virus infection and in those without. Hepatitis B surface antigen (HBsAg) was detected in five (2%) out of 285 patients studied and antibody to HBsAg (anti-HBs) in 41 (14%); one patient had antibody to hepatitis B core antigen alone. The combined prevalence of markers of hepatitis B virus infection was similar in patients with alcoholic cirrhosis (18%) and precirrhotic liver disease (13%). Two patients positive for HBsAg had histological features of both alcoholic liver disease and chronic active hepatitis, with stainable HBsAg. Patients with anti-HBs were, however, histologically indistinguishable from patients without markers, and the mean cumulative alcohol intake of patients with anti-HBs was similar to or even higher than that of patients with liver disease of comparable severity who had no evidence of previous infection. The presence of markers of hepatitis B virus infection was related to former residence in countries with a high prevalence of the infection and to previous parenteral treatment and blood transfusions. Infection with hepatitis B virus does not enhance the development of chronic liver disease in heavy drinkers, except in the small number who remain positive for HBsAg. PMID:6407600

Saunders, J B; Wodak, A D; Morgan-Capner, P; White, Y S; Portmann, B; Davis, M; Williams, R

1983-01-01

58

Acute hepatitis C in HIV-positive individuals.  

PubMed

Due to the asymptomatic nature of acute hepatitis C it can be difficult to diagnose in the early stage of infection, but with the higher treatment success rates and reduced treatment duration at this stage, it is imperative that diagnoses are made. Therefore, physicians should routinely screen at-risk individuals and investigate abnormal liver function tests. Serum HCV RNA should be considered in any HCV-antibody-negative individual in whom acute HCV is clinically suspected, or annually in those high-risk individuals with previous infection. Acute hepatitis C transmission may be facilitated by the presence of an erosive genital lesion, such as syphilis or lymphogranuloma venereum, and thus testing at this time should be encouraged. Reinfection with HCV does occur and patients need to be informed of the sexual and other high-risk behaviors that put them at risk of reinfection. Public awareness of the possibility of HCV infection, and subsequent reinfection, in high-risk groups should be increased. The question of the optimal treatment regimen is still disputed. However, ongoing trials and the proposed randomized controlled trial from the European AIDS Treatment Network should answer many of our questions. In the meantime, units faced with HIV/acute hepatitis C coinfection should follow recommendations from the HCV-HIV International Panel. PMID:19092980

Low, Emma; Vogel, Martin; Rockstroh, Jürgen; Nelson, Mark

2008-01-01

59

SHORT REPORT Open Access Acute risk for hepatitis E virus infection among  

E-print Network

SHORT REPORT Open Access Acute risk for hepatitis E virus infection among HIV-1-positive pregnant: Hepatitis E virus (HEV), an enterically transmitted pathogen, is highly endemic in several African countries. Pregnant women are at particularly high risk for acute or severe hepatitis E. In Gabon, a central African

Paris-Sud XI, Université de

60

Butachlor-induced acute toxic hepatitis.  

PubMed

Butachlor is a highly effective herbicidal substance widely used by farmers. We report a 60-year-old man with exfoliative dermatitis, jaundice, increase in liver enzymes and eosinophilia one day after accidental dermal exposure to butachlor toxin. The diagnostic workup showed no other cause and liver histology was consistent with substance-induced toxic hepatitis. Within two weeks of conservative therapy, his liver function tests returned to normal. PMID:17704582

Daryani, Nasser Ebrahimi; Hosseini, Parviz; Bashashati, Mohammad; Haidarali, Mona; Sayyah, Alireza

2007-01-01

61

Acute Drug-Induced Hepatitis Caused by Albendazole  

PubMed Central

Albendazole binds to parasite's tubulin inhibiting its glucose absorption. Its common adverse effects are nausea, vomiting, constipation, thirst, dizziness, headache, hair loss and pruritus. Although mainly metabolized in the liver, abnormal liver function tests were a rare adverse effect during clinical trials and we found no literature about albendazole-induced hepatitis requiring admission. This patient had a previous history of albendazole ingestion in 2002 resulting in increase of liver function tests. And in 2005, the episode repeated. We evaluated the patient for viral hepatitis, alcoholic liver disease, and autoimmune hepatitis, but no other cause of hepatic injury could be found. Liver biopsy showed periportal steatosis and periportal necrosis. The initial abnormal liver function test improved only with supportive care. These findings and the Roussel Uclaf Causality Assessment Method of the Council for International Organizations of Medical Sciences (RUCAM/CIOMS) score of 9 are compatible with drug-induced hepatitis so we report the case of this patient with a review of the literature. PMID:18955802

Choi, Gi Young; Cho, Soung Hoon; Kang, Dong Wook; Go, Hoon; Lee, Woong Chul; Lee, Yun Jung; Jung, Sung Hee; Kim, An Na; Cha, Sang Woo

2008-01-01

62

ECG-voltage in alcoholics and non-alcoholics with acute alcohol intoxication  

Microsoft Academic Search

Alcohol intoxication is probably the most common intoxication worldwide, and may be lethal. The exact mechanism by which ethanol intoxication contributes to death is unknown, although ventricular tachyarrhythmias degenerating into fibrillation is a possible cause. Alcoholics have increased risk of sudden death and, possibly, higher risk than occasional drinkers. In 32 consecutive patients with alcohol intoxication ?-voltage was the differences

Willy Aasebø

2009-01-01

63

Hepatitis E virus in patients with acute severe liver injury  

PubMed Central

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

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

2014-01-01

64

Low dose acute alcohol effects on GABAA receptor subtypes  

PubMed Central

GABAA receptors (GABAARs) are the main inhibitory neurotransmitter receptors and have long been implicated in mediating at least part of the acute actions of ethanol. For example, ethanol and GABAergic drugs including barbiturates and benzodiazepines share many pharmacological properties. Besides the prototypical synaptic GABAAR subtypes, nonsynaptic GABAARs have recently emerged as important regulators of neuronal excitability. While high doses (?100 mM) of ethanol have been reported to enhance activity of most GABAAR subtypes, most abundant synaptic GABAARs are essentially insensitive to ethanol concentrations that occur during social ethanol consumption (<30 mM). However, extrasynaptic ? and ?3 subunit-containing GABAARs, associated in the brain with ?4or ?6 subunits, are sensitive to low millimolar ethanol concentrations, as produced by drinking half a glass of wine. Additionally, we found that a mutation in the cerebellar ?6 subunit (?6R100Q), initially reported in rats selectively bred for increased alcohol sensitivity, is sufficient to produce increased alcohol-induced motor impairment and further increases of alcohol sensitivity in recombinant ?6?3? receptors. Furthermore, the behavioral alcohol antagonist Ro15-4513 blocks the low dose alcohol enhancement on ?4/6/?3? receptors, without reducing GABA-induced currents. In binding assays ?4?3? GABAARs bind [3H] Ro15-4513 with high affinity, and this binding is inhibited, in an apparently competitive fashion, by low ethanol concentrations, as well as analogs of Ro15-4513 that are active to antagonize ethanol or Ro15-4513’s block of ethanol. We conclude that most low to moderate dose alcohol effects are mediated by alcohol actions on alcohol/Ro15-4513 binding sites on GABAAR subtypes. PMID:16814864

Wallner, Martin; Hanchar, H. Jacob; Olsen, Richard W.

2010-01-01

65

Molecular Mechanisms of Alcohol-Induced Hepatic Fibrosis  

Microsoft Academic Search

Alcohol abuse is a major cause of liver fibrosis and cirrhosis in developed countries. Before alcoholic liver fibrosis becomes evident, the liver undergoes several stages of alcoholic liver disease including steatosis and steatohepatitis. Although the main mechanisms of fibrogenesis are independent of the etiology of liver injury, alcoholic liver fibrosis is distinctively characterized by a pronounced inflammatory response due to

Sören V. Siegmund; Steven Dooley; David A. Brenner

2005-01-01

66

Acute alcohol impairs human goal-directed action.  

PubMed

There are two forms of motivated behaviour. Goal-directed action is mediated by knowledge of the consequences whereas habitual action is elicited directly by stimuli associated with the action. Alcohol may impair goal-directed control, favouring habit. To evaluate this proposal, participants were administered with 0.4 g/kg of alcohol or placebo before acquiring separate instrumental responses for chocolate and water points. Chocolate was then fed to satiety to devalue this outcome before choice between the two responses was tested in extinction. Any reduction in chocolate choice must be mediated by knowledge of the current incentive value of this outcome, i.e. must be goal-directed. Alcohol attenuated the devaluation effect on choice in extinction, but had no effect on reacquisition performance, the hedonic appraisal of rewards or acquisition of the instrumental contingencies. Acute alcohol impaired goal-directed control of action selection, favouring habit, which may mediate alcohol effects on under-controlled behaviour more broadly. PMID:22406757

Hogarth, Lee; Attwood, Angela S; Bate, Helen A; Munafò, Marcus R

2012-05-01

67

Effects of cysteine and antioxidants on the hepatic redox-state, acetaldehyde and triglyceride levels after acute ethanol dosing.  

PubMed

Cysteine and the synthetic antioxidants butylated hydroxytoluene (BHT) and N,N'-diphenyl-phenylenediamine (DPPD) have been found to protect against the increase in hepatic triglycerides caused by acute ethanol administration (2 g/kg/i.p.) in rats. None of these agents affected the ethanol-induced increase in the hepatic redox-state, measured as lactate/pyruvate and 3-hydroxybutyrate/acetoacetate ratios, and there was no influence of any of the compounds on ethanol metabolism. Of the three agents tested, only cysteine was found to lower the liver acetaldehyde concentration after ethanol administration, confirming reports that trapping of acetaldehyde can protect against ethanol hepatotoxicity. The protective action of the anti-oxidants suggests that lipid peroxidation (probably initiated by acetaldehyde) is an important event in the pathogenesis of acute alcoholic fatty liver. PMID:3426693

Ryle, P R; Chakraborty, J; Thomson, A D

1987-01-01

68

[Acute hepatitis associated with Colpachi intake. Apropros of 5 cases].  

PubMed

The use of herbal medicines believed to have therapeutic properties is becoming increasingly widespread. These medicines are usually taken by patients on their own initiative and physicians are often unaware of which patients are taking these substances. Herbal medicines can be taken in the form of teas, powders, and liquid extracts. In the last few years, it has come to light that these natural remedies are not free of risks, especially the risk of interaction with other drugs or hepatotoxicity, ranging from asymptomatic forms to massive hepatic necrosis. We describe a series of 5 patients notified to the Spanish Pharmacovigilance System of medicinal products for human use. All the patients developed acute hepatitis during Colpachi treatment lasting several months, which resolved after discontinuing intake of this substance. Systematic examination of the literature revealed the existence of 6 other reported cases of suspected Colpachi-induced hepatotoxicity. PMID:17335712

Bruguera, Miguel; Herrera, Samuel; Lázaro, Edurne; Madurga, Mariano; Navarro, Marta; de Abajo, Francisco J

2007-02-01

69

Recovery and Sequence Analysis of Hepatitis A Virus from Springwater Implicated in an Outbreak of Acute Viral Hepatitis?  

PubMed Central

An outbreak of acute hepatitis A virus in North Carolina was linked to drinking water from a contaminated shallow spring by phylogenetic analysis of hepatitis A virus (HAV) genomic sequences. Detection of HAV and fecal indicators in the water provided useful and timely information to assist with public health prevention and control measures. PMID:18708522

Tallon, Lindsay A.; Love, David C.; Moore, Zack S.; Sobsey, Mark D.

2008-01-01

70

Inhibitory effect of liposomal quercetin on acute hepatitis and hepatic fibrosis induced by concanavalin A  

PubMed Central

Immune response plays an important role in the development of hepatic fibrosis. In the present study, we investigated the effects of quercetin on hepatitis and hepatic fibrosis induced by immunological mechanism. In the acute hepatitis model, quercetin (2.5 mg/kg) was injected iv into mice 30 min after concanavalin A (Con A) challenge. Mice were sacrificed 4 or 24 h after Con A injection, and aminotransferase tests and histopathological sections were performed. Treatment with quercetin significantly decreased the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Consistent with this observation, treatment with quercetin markedly attenuated the pathologic changes in the liver. A hepatic fibrosis model was also generated in mice by Con A challenge once a week for 6 consecutive weeks. Mice in the experimental group were treated with daily iv injections of quercetin (0.5 mg/kg). Histopathological analyses revealed that treatment with quercetin markedly decreased collagen deposition, pseudolobuli development, and hepatic stellate cells activation. We also examined the effects of quercetin on the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) and transforming growth factor beta (TGF-?) pathways by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR). NF-?B and TGF-? production was decreased after treatment with quercetin, indicating that the antifibrotic effect of quercetin is associated with its ability to modulate NF-?B and TGF-? production. These results suggest that quercetin may be an effective therapeutic strategy in the treatment of patients with liver damage and fibrosis. PMID:25098714

Wan, Y.; Tang, M.H.; Chen, X.C.; Chen, L.J.; Wei, Y.Q.; Wang, Y.S.

2014-01-01

71

Alcohol and porphyrin metabolism.  

PubMed

Alcohol is a porphyrinogenic agent which may cause disturbances in porphyrin metabolism in healthy persons as well as biochemical and clinical manifestations of acute and chronic hepatic porphyrias. After excessive consumption of alcohol, a temporary, clinically asymptomatic secondary hepatic coproporphyrinuria is observable, which can become persistent in cases of alcohol-induced liver damage. Nowadays, the alcohol-liver-porphyrinuria syndrome is the first to be mentioned in secondary hepatic disturbances of porphyrin metabolism. Acute hepatic porphyrias (acute intermittent porphyria, variegate porphyria and hereditary coproporphyria) are considered to be molecular regulatory diseases, in contrast to non-acute, chronic hepatic porphyria, clinically appearing as porphyria cutanea tarda (PCT). Porphyrins do not accumulate in the liver in acute porphyrias, whereas in chronic hepatic porphyrias they do. Thus, chronic hepatic porphyria is a porphyrin-accumulation disease, whereas acute hepatic porphyrias are haem-pathway-dysregulation diseases, characterized in general by induction of delta-aminolevulinic acid synthase in the liver and excessive stimulation of the pathway without storage of porphyrins in the liver. The clinical expression of acute hepatic porphyrias can be triggered by alcohol, because alcohol augments the inducibility of delta-aminolevulinic acid synthase. In chronic hepatic porphyrias, however, which are already associated with liver damage, alcohol potentiates the disturbance of the decarboxylation of uro- and heptacarboxyporphyrinogen, which is followed by a hepatic accumulation of uro- and heptacarboxyporphyrin and their sometimes extreme urinary excretion. Especially in persons with a genetic deficiency of uroporphyrinogen decarboxylase, but also in patients with the so-called sporadic variety of PCT, alcohol is able to transform an asymptomatic coproporphyrinuria into PCT. Alcohol has many biochemical and clinical effects on porphyrin and haem synthesis both in humans and laboratory animals. Ethanol suppresses the activity of porphobilinogen synthase (synonym: delta-aminolevulinic acid dehydratase), uroporphyrinogen decarboxylase, coproporphyrinogen oxidase and ferrochelatase, whereas it induces the first and rate-limiting enzyme in the pathway, delta-aminolevulinic acid synthase and also porphobilinogen deaminase. Therefore, teetotalism is a therapeutically and prophylactically important measure in all types of hepatic porphyrias. PMID:10787385

Doss, M O; Kühnel, A; Gross, U

2000-01-01

72

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

PubMed

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

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

2015-02-25

73

Erythropoietic and hepatic porphyrias.  

PubMed

Porphyrias are divided into erythropoietic and hepatic manifestations. Erythropoietic porphyrias are characterized by cutaneous symptoms and appear in early childhood. Erythropoietic protoporphyria is complicated by cholestatic liver cirrhosis and progressive hepatic failure in 10%, of patients. Acute hepatic porphyrias (delta-aminolaevulinic acid dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria and variegate porphyria) are characterized by variable extrahepatic gastrointestinal, neurological-psychiatric and cardiovascular manifestations requiring early diagnosis to avoid life-threatening complications. Acute hepatic porphyrias are pharmacogenetic and molecular regulatory diseases (without porphyrin accumulation) mainly induced by drugs, sex hormones, fasting or alcohol. The disease process depends on the derepression of hepatic delta-aminolaevulinic acid synthase following haem depletion. In contrast to the acute porphyrias, nonacute, chronic hepatic porphyrias such as porphyria cutanea tarda are porphyrin accumulation disorders leading to cutaneous symptoms associated with liver disease, especially caused by alcohol or viral hepatitis. Alcohol, oestrogens, haemodialysis, hepatitis C and AIDS are triggering factors. Porphyria cutanea tarda is the most common porphyria, followed by acute intermittent porphyria and erythropoietic protoporphyria. The molecular genetics of the porphyrias is very heterogenous. Nearly every family has its own mutation. The mutations identified account for the corresponding enzymatic deficiencies, which may remain clinically silent throughout life. Thus, the recognition of the overt disorder with extrahepatic manifestations depends on the demonstration of biochemical abnormalities due to these primary defects and compensatory hepatic overexpression of hepatic delta-aminolaevulinic acid synthase in the acute porphyrias. Consequently, haem precursors are synthesized in excess. The increased metabolites upstream of the enzymatic defect are excreted into urine and faeces. The diagnosis is based on their evaluation. Primary enzymatic or molecular analyses are noncontributary and may be misleading. Acute polysymptomatic exacerbations accompany a high excretory constellation of porphyrin precursors delta-aminolaevulinic acid and porphobilinogen. Homozygous or compound heterozygous variants of acute hepatic porphyrias may already manifest in childhood. PMID:11117426

Gross, U; Hoffmann, G F; Doss, M O

2000-11-01

74

Safety of general anaesthesia and surgery in acute hepatic porphyria.  

PubMed Central

Patients with acute hepatic porphyria are denied essential operations because of concern that general anaesthesia and surgery will precipitate a life threatening porphyric crisis. This study assessed the safety of surgery under general anaesthesia in these patients. A combined prospective and retrospective case note study, with a biochemical study, was conducted in 25 patients with acute hepatic porphyria undergoing 38 surgical operations. Clinical outcome measures were survival and occurrence of porphyric crisis after surgery. The biochemical activity of porphyria was assessed by measurement of the perioperative 24 hour excretion of the haem precursors delta amino-laevulinic acid (ALA) and porphobilinogen (PBG). There were no deaths or crises after 29 operations in 19 patients who were known to have porphyria before their surgery, and therefore given only appropriate drugs. These operations include such major procedures as mitral valve replacement, hip replacement, coronary artery grafting, cholecystectomies, and renal transplantation. In eight of these patients the urinary excretion of ALA and PBG were studied, and showed no sustained postoperative increase. Nine operations were performed in eight patients before the diagnosis of porphyria was known and who thus received routine anaesthetic agents. Seven of these patients developed a postoperative porphyric crisis. Two of them died. It is concluded therefore that even the most major surgery can be undertaken safely in patients with porphyria. The risk is for undiagnosed cases. PMID:7926916

Dover, S B; Plenderleith, L; Moore, M R; McColl, K E

1994-01-01

75

Polyphyletic Strains of Hepatitis E Virus Are Responsible for Sporadic Cases of Acute Hepatitis in Japan  

PubMed Central

Among 87 patients who were previously treated for acute hepatitis of unknown etiology between 1992 and 2001 at five hospitals in Japan, 11 (13%) patients were positive for immunoglobulin M-class antibodies to hepatitis E virus (HEV) by enzyme immunoassay and had detectable HEV RNA by reverse transcription-PCR with two independent sets of primers derived from well-conserved genomic areas in open reading frames 1 and 2. Clinical HEV infection was significantly associated with male sex (9 of 11 versus 29 of 76 patients [P < 0.01]) and older age (52 ± 11 [mean ± standard deviation] versus 41 ± 17 years [P < 0.05]), and its prevalence differed by geographic region (6 to 25%), with a higher rate in the northern part of Japan. At admission, the 11 patients with HEV-associated hepatitis had elevated alanine aminotransferase levels of 914 to 4,850 IU/liter, and all but 1 had elevated bilirubin levels of 1.5 to 24.0 mg/dl. The 11 HEV isolates were of genotype III or IV and were segregated into three groups with intergroup nucleotide differences of 9.5 to 22.0%. Phylogenetic analysis revealed that four isolates of genotype III were closely related to a Japanese isolate, while the other four isolates of the same genotype were nearest those from the United States. The remaining three isolates were close to known isolates of genotype IV in China and Taiwan but shared less than 88% identity with them. These results indicate that multiple genotypes of HEV cocirculate in Japan and contribute to the development of sporadic acute hepatitis, with the prevalence differing by age, sex, and geographic region. PMID:12202555

Mizuo, Hitoshi; Suzuki, Kazuyuki; Takikawa, Yasuhiro; Sugai, Yoshiki; Tokita, Hajime; Akahane, Yoshihiro; Itoh, Keiichi; Gotanda, Yuhko; Takahashi, Masaharu; Nishizawa, Tsutomu; Okamoto, Hiroaki

2002-01-01

76

Acute seronegative hepatitis C manifesting itself as adult giant cell hepatitis--a case report and review of literature.  

PubMed

Adult giant cell hepatitis (AGCH) is a rare event and only about 100 cases have been reported within the last 20 years. The AGCH has been observed in association with viral infection, drug reactions or autoimmune disorders but in many cases its etiology remains unclear. AGCH manifests clinically as severe form of hepatitis histologically characterized by diffuse giant cell transformation of hepatocytes. We report the case of a 39-yr-old man with acute community-acquired hepatitis without previous pathology of the liver. Laboratory data revealed slight hypergammaglobulinemia and high titer of anti-smooth-muscle antibody with negative serology of hepatotropic viruses and absence of other known causes of hepatitis. Preliminary diagnosis of autoimmune hepatitis was established, additionally confirmed by excellent clinical and biochemical improvement during corticosteroid treatment. A liver biopsy showed the typical findings of panlobular syncytial giant cell hepatitis and positive HCV-RNA both in serum and liver. The above verified the diagnosis of acute type C hepatitis manifested histologically as adult giant cell hepatitis. After three months of treatment we withdrew corticosteroids as spontaneous clearance of HCV occurred and the lack of autoantibodies in serum as well as significant improvement of liver histology was ascertained. Within 30 months of the follow-up we have not observed biochemical and immunological abnormalities and control liver biopsy has shown no signs of hepatitis. PMID:15156608

Kryczka, Wies?aw; Walewska-Zielecka, Bozena; Dutkiewicz, Ewa

2003-08-01

77

Epstein-barr virus infection with acute pancreatitis associated with cholestatic hepatitis.  

PubMed

Infection-induced acute hepatitis complicated with acute pancreatitis is associated with hepatitis A virus, hepatitis B virus or hepatitis E virus. Although rare, Epstein-Barr virus (EBV) infection should be considered also in the differential diagnosis if the patient has acute hepatitis combined with pancreatitis. We report a case of EBV infection with cholestatic hepatitis and pancreatitis with review of literature. An 11-year-old female was admitted due to 1-day history of abdominal pain and vomiting without any clinical symptoms of infectious mononucleosis. Diagnosis of reactivated EBV infection was made by the positive result of viral capsid antigen (VCA) IgM, VCA IgG, Epstein-Barr nuclear antigen and heterophile antibody test. We performed serologic tests and magnetic resonance cholangiopancreatography to exclude other viral or bacterial infection, autoimmune disorder, and structural problems. The patient's symptoms recovered rapidly and blood chemistry returned to normal with conservative treatment similar to previously reported cases. PMID:24010108

Kang, Seok-Jin; Yoon, Ka-Hyun; Hwang, Jin-Bok

2013-03-01

78

Acute Effects of Alcohol on Intrusive Memory Development and Viewpoint Dependence in Spatial  

E-print Network

Words: Alcohol, allocentric, hippocampus, intrusions, post- traumatic stress disorder (PTSD) A primaryAcute Effects of Alcohol on Intrusive Memory Development and Viewpoint Dependence in Spatial Memory the effect of alcohol on intrusive memories and, concurrently, on egocentric and allocentric spatial memory

Burgess, Neil

79

Iron overload facilitates hepatic fibrosis in the rat alcohol\\/low-dose carbon tetrachloride model  

Microsoft Academic Search

The role of iron deposition in initiating hepatic fibrosis in iron overload disorders is not clearly established, and it is becoming increasingly recognized that iron may be interacting with other potential liver-damaging agents. The authors therefore examined the interplay of iron and alcohol in rats administered subtoxic doses of carbon tetrachloride (CCL4) vapor at 20 ppm in customized chambers. At

Malcolm MacKinnon; Cindy Clayton; John Plummer; Michael Ahern; Patricia Cmielewski; Anthony Ilsley; Pauline Hall

1995-01-01

80

Clinical Features of Adult Patients with Acute Hepatitis B Virus Infection Progressing to Chronic Infection  

PubMed Central

Background. Information regarding the progression of acute hepatitis B virus (HBV) infection to chronic infection in adults is scarce. Methods. Twenty-five adult patients with acute HBV infection (14 men and 11 women, 18–84 years old), whose clinical features progressed to those of chronic infection (group A) or did not (group B), were studied retrospectively. Results. There were 3 and 22 patients in groups A and B, respectively. Two of the 3 patients of group A lacked the typical symptoms of acute hepatitis. No differences were found between groups with respect to age, sex, or HBV genotypes. However, total bilirubin and alanine aminotransaminase levels were significantly lower in group A. Conclusions. Three of the 25 adult patients with acute HBV infection progressed to chronic infection. Hepatitis was mild in these patients. Patients with mild acute hepatitis B or unapparent HBV infection may have a higher risk of progressing to chronic infection. PMID:25349743

Michitaka, Kojiro; Hiraoka, Atsushi; Tokumoto, Yoshio; Ninomiya, Keiko; Ninomiya, Tomoyuki; Horiike, Norio

2014-01-01

81

Alcohol alters hepatic FoxO1, p53, and mitochondrial SIRT5 deacetylation function  

SciTech Connect

Chronic alcohol consumption affects the gene expression of a NAD-dependent deacetylase Sirtuis 1 (SIRT1) and the peroxisome proliferator-activated receptor-{gamma} coactivator1{alpha} (PGC-1{alpha}). Our aim was to verify that it also alters the forkhead (FoxO1) and p53 transcription factor proteins, critical in the hepatic response to oxidative stress and regulated by SIRT1 through its deacetylating capacity. Accordingly, rats were pair-fed the Lieber-DeCarli alcohol-containing liquid diets for 28 days. Alcohol increased hepatic mRNA expression of FoxO1 (p = 0.003) and p53 (p = 0.001) while corresponding protein levels remained unchanged. However phospho-FoxO1 and phospho-Akt (protein kinase) were both decreased by alcohol consumption (p = 0.04 and p = 0.02, respectively) while hepatic p53 was found hyperacetylated (p = 0.017). Furthermore, mitochondrial SIRT5 was reduced (p = 0.0025), and PGC-1{alpha} hyperacetylated (p = 0.027), establishing their role in protein modification. Thus, alcohol consumption disrupts nuclear-mitochondrial interactions by post-translation protein modifications, which contribute to alteration of mitochondrial biogenesis through the newly discovered reduction of SIRT5.

Lieber, Charles S. [Section of Liver Disease and Nutrition, James J. Peters VA Medical Center, 130 West Kingsbridge Road (151-2), Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States)], E-mail: liebercs@aol.com; Leo, Maria Anna [Section of Liver Disease and Nutrition, James J. Peters VA Medical Center, 130 West Kingsbridge Road (151-2), Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Wang, Xiaolei [Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); DeCarli, Leonore M. [Section of Liver Disease and Nutrition, James J. Peters VA Medical Center, 130 West Kingsbridge Road (151-2), Bronx, NY 10468 (United States)

2008-08-22

82

Transient receptor potential vanilloid 1 gene deficiency ameliorates hepatic injury in a mouse model of chronic binge alcohol-induced alcoholic liver disease.  

PubMed

Experimental alcohol-induced liver injury is exacerbated by a high polyunsaturated fat diet rich in linoleic acid. We postulated that bioactive oxidized linoleic acid metabolites (OXLAMs) play a critical role in the development/progression of alcohol-mediated hepatic inflammation and injury. OXLAMs are endogenous ligands for transient receptor potential vanilloid 1 (TRPV1). Herein, we evaluated the role of signaling through TRPV1 in an experimental animal model of alcoholic liver disease (ALD). Chronic binge alcohol administration increased plasma OXLAM levels, specifically 9- and 13-hydroxy-octadecadienoic acids. This effect was associated with up-regulation of hepatic TRPV1. Exposure of hepatocytes to these OXLAMs in vitro resulted in activation of TRPV1 signal transduction with increased intracellular Ca(2+) levels. Genetic depletion of TRPV1 did not blunt hepatic steatosis caused by ethanol, but prevented hepatic injury. TRPV1 deficiency protected from hepatocyte death and prevented the increase in proinflammatory cytokine and chemokine expression, including tumor necrosis factor-?, IL-6, macrophage inflammatory protein-2, and monocyte chemotactic protein 1. TRPV1 depletion markedly blunted ethanol-mediated induction of plasminogen activator inhibitor-1, an important alcohol-induced hepatic inflammation mediator, via fibrin accumulation. This study indicates, for the first time, that TRPV1 receptor pathway may be involved in hepatic inflammatory response in an experimental animal model of ALD. TRPV1-OXLAM interactions appear to play a significant role in hepatic inflammation/injury, further supporting an important role for dietary lipids in ALD. PMID:25447051

Liu, Huilin; Beier, Juliane I; Arteel, Gavin E; Ramsden, Christopher E; Feldstein, Ariel E; McClain, Craig J; Kirpich, Irina A

2015-01-01

83

Acute Posttransfusion Hepatitis C: Identification of a Common Hepatitis C Virus Strain in Donor and Recipient Using Polymorphism Analysis  

Microsoft Academic Search

An 11-year-old Thai boy who had received multiple blood transfusions from 12 different donors for treatment of Dengue shock\\u000a syndrome presented with symptoms of acute hepatitis 5 weeks thereafter. He was found positive for antibodies to hepatitis\\u000a C virus (HCV) and HCV-RNA was detected by reverse transcription PCR (RT-PCR). When his alanine aminotransferase (ALT) level\\u000a peaked at 1,879 U\\/l in

T. Chinchai; S. Noppornpanth; A. Theamboonlers; V. Chongsrisawat; Y. Poovorawan

2001-01-01

84

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

PubMed Central

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

2014-01-01

85

Chunggan extract, a traditional herbal formula, ameliorated alcohol-induced hepatic injury in rat model  

PubMed Central

AIM: To evaluate protective effects of Chunggan extract (CGX), a traditional herbal formula, under 4 wk of alcohol consumption-induced liver injury. METHODS: Male Sprague-Dawley Rats were orally administered 30% ethanol daily for 4 wk with or without CGX. The pharmaceutical properties were assessed through liver enzymes, histopathology, fibrogenic cytokines, and alcohol metabolism in hepatic tissues as well as by in vitro experiment using HSC-T6 cells. RESULTS: Four weeks of alcohol consumption notably increased liver enzymes and malondialdehyde levels in serum and hepatic tissue. CGX not only prevented the collagen deposition determined by histopathology and hydroxyproline content, but also normalized transforming growth factor-beta, platelet-derived growth factor-beta and connective tissue growth factor at the gene expression and protein levels in liver tissue. Moreover, CGX treatment also significantly normalized the abnormal changes in gene expression profiles of extracellular matrix proteins, matrix metalloproteinase and their inhibitors, alcohol metabolism, and inflammatory reactions. In the acetaldehyde-stimulated HSC-T6 cells, CGX considerably inhibited collagen production and normalized fibrogenic cytokines in both gene expression and protein levels. CONCLUSION: The present study evidenced that CGX has hepatoprotective properties via modulation of fibrogenic cytokines and alcohol metabolism in alcoholic liver injury. PMID:25400454

Kim, Hyeong-Geug; Kim, Jung-Min; Han, Jong-Min; Lee, Jin-Seok; Choi, Min-Kyung; Lee, Dong-Soo; Park, Yeon-Hwa; Son, Chang-Gue

2014-01-01

86

The effects of acute alcohol administration on the human brain: Insights from neuroimaging  

PubMed Central

Over the last quarter century, researchers have peered into the living human brain to develop and refine mechanistic accounts of alcohol-induced behavior, as well as neurobiological mechanisms for development and maintenance of addiction. These in vivo neuroimaging studies generally show that acute alcohol administration affects brain structures implicated in motivation and behavior control, and that chronic intoxication is correlated with structural and functional abnormalities in these same structures, where some elements of these decrements normalize with extended sobriety. In this review, we will summarize recent findings about acute human brain responses to alcohol using neuroimaging techniques, and how they might explain behavioral effects of alcohol intoxication. We then briefly address how chronic alcohol intoxication (as inferred from cross-sectional differences between various drinking populations and controls) may yield individual brain differences between drinking subjects that may confound interpretation of acute alcohol administration effects. PMID:23978384

Bjork, James M.; Gilman, Jodi M.

2014-01-01

87

Blood alcohol concentration and self-reported alcohol ingestion in acute poisoned patients who visited an emergency department  

PubMed Central

Background Many acute poisoned patients have co-ingested alcohol in the emergency department (ED). This study aimed to estimate the blood alcohol concentration (BAC) of acute poisoned patients who visited an ED by age and gender distribution and to determine whether it is possible to obtain self-reports of alcohol ingestion among poisoned patients. Method A retrospective medical chart review was conducted for all patients who visited the ED with acute poisoning between January 2004 and February 2008. Data regarding the patient’s age, gender, BAC, self-reported alcohol ingestion, poison ingested, time elapsed since poison exposure, presence of suicide attempts, and self-reported alcohol ingestion were collected. Patients were classified into two groups based on serum alcohol levels (?10 mg/dl, >10 mg/dl). Results Of the 255 subjects, 88 subjects (34.5%) were included in the non-alcohol group and 167 subjects (65.5%) were included in the alcohol group. 227 subjects (89.0%) showed suicide intention. Using the 201 subjects who completed the self-report of alcohol ingestion, self-report resulted in 96.6% sensitivity and 86.7% specificity for the assessment of alcohol ingestion. The positive and negative predictive values for self-report were 91.2% and 94.7%, respectively. The median (interquartile range) BAC of the 97 males in the sample was 85.0 (10.0-173.5) mg/dl, and that of the 158 females was 32.0 (4.0-137.5) mg/dl (p?=?0.010). The distribution of age in the groups was significantly different between the alcohol and non-alcohol groups (p?=?0.035), and there was a significant difference in the mean BAC with respect to age for males (p?=?0.003). Conclusion This study showed that over two-thirds of patients presenting with acute poisoning had a BAC?>?10 mg/dl. Most of patients visited by suicide attempt. Males had a higher BAC than did females. Self-reported alcohol ingestion in acute poisoned patients showed high sensitivity and specificity. PMID:23574916

2013-01-01

88

Relative effects of heavy alcohol use and Hepatitis C in decompensated chronic liver disease in a hospital inpatient population.  

PubMed

Abstract Background: Heavy alcohol use has been hypothesized to accelerate disease progression to end-stage liver disease in patients with hepatitis C virus (HCV) infection. In this study, we estimated the relative influences of heavy alcohol use and HCV in decompensated chronic liver disease (CLD). Methods: Retrospectively, 904 patients with cirrhotic disease admitted to our hospitals during January 2010-December 2012 were identified based on ICD9 codes. A thorough chart review captured information on demographics, viral hepatitis status, alcohol use and progression of liver disease (i.e. decompensation). Decompensation was defined as the presence of ascites due to portal hypertension, bleeding esophageal varices, hepatic encephalopathy or hepatorenal syndrome. Heavy alcohol use was defined as a chart entry of greater than six daily units of alcohol or its equivalent. Results: 347 patients were included based on our selection criteria of documented heavy alcohol use (n?=?215; 62.0%), hepatitis titers (HCV: n?=?182; 52.5%) and radiological evidence of CLD with or without decompensation (decompensation: n?=?225; 64.8%). Independent of HCV infection, heavy alcohol use significantly increased the risk of decompensation (OR?=?1.75, 95% CI 1.11-2.75, p?alcohol use. No significance was seen with age, sex, race, HIV, viral hepatitis and moderate alcohol use for risk for decompensation. Additionally, dose-relationship regression analysis revealed that heavy, but not moderate alcohol use, resulted in a three-fold increase (p?=?0.013) in the risk of decompensation relative to abstinence. Conclusions: While both heavy alcohol use and HCV infection are associated with risk of developing CLD, our data suggest that heavy, but not moderate, alcohol consumption is associated with a greater risk for hepatic decompensation in patients with cirrhosis than does HCV infection. PMID:25320839

Mankal, Pavan Kumar; Abed, Jean; Aristy, Jose David; Munot, Khushboo; Suneja, Upma; Engelson, Ellen S; Kotler, Donald P

2014-10-16

89

Acute Alcohol Effects on Neuronal and Attentional Processing: Striatal Reward System and Inhibitory Sensory Interactions under Acute Ethanol Challenge  

Microsoft Academic Search

The acute influence of ethanol on cerebral activity induces complex psycho-physiological effects that are considerably more pronounced during acute ethanol influx than during maximal blood alcohol concentration (elimination phase). Despite the psychiatric and forensic relevance of these different ethanol effects, the underlying neuronal mechanisms are still unclear. In total, 20 male healthy volunteers were investigated each with three different experimental

Mathias Schreckenberger; Rainer Amberg; Armin Scheurich; Matthias Lochmann; Wolfgang Tichy; André Klega; Thomas Siessmeier; Gerhard Gründer; Hans-Georg Buchholz; Christian Landvogt; Jan Stauss; Klaus Mann; Peter Bartenstein; Reinhard Urban

2004-01-01

90

Immunological and molecular epidemiological characteristics of acute and fulminant viral hepatitis A  

PubMed Central

Background Hepatitis A virus is an infection of liver; it is hyperendemic in vast areas of the world including India. In most cases it causes an acute self limited illness but rarely fulminant. There is growing concern about change in pattern from asymptomatic childhood infection to an increased incidence of symptomatic disease in the adult population. Objective In-depth analysis of immunological, viral quantification and genotype of acute and fulminant hepatitis A virus. Methods Serum samples obtained from 1009 cases of suspected acute viral hepatitis was employed for different biochemical and serological examination. RNA was extracted from blood serum, reverse transcribed into cDNA and amplified using nested PCR for viral quantification, sequencing and genotyping. Immunological cell count from freshly collected whole blood was carried out by fluorescence activated cell sorter. Results Fulminant hepatitis A was mostly detected with other hepatic viruses. CD8+ T cells count increases in fulminant hepatitis to a significantly high level (P = 0.005) compared to normal healthy control. The immunological helper/suppressor (CD4+/CD8+) ratio of fulminant hepatitis was significantly lower compared to acute cases. The serologically positive patients were confirmed by RT-PCR and total of 72 (69.2%) were quantified and sequenced. The average quantitative viral load of fulminant cases was significantly higher (P < 0.05). There was similar genotypic distribution in both acute and fulminant category, with predominance of genotype IIIA (70%) compared to IA (30%). Conclusions Immunological factors in combination with viral load defines the severity of the fulminant hepatitis A. Phylogenetic analysis of acute and fulminant hepatitis A confirmed genotypes IIIA as predominant against IA with no preference of disease severity. PMID:21605420

2011-01-01

91

Acute and chronic alcohol administration: Effects on performance of zebrafish in a latent learning task.  

PubMed

Alcohol abuse is a major medical problem. Zebrafish have been proposed to model alcohol related human disorders. Alcohol impairs learning and memory. Here, we analyze the effects of alcohol on performance of zebrafish in a recently developed latent learning paradigm. We employ a 2×3×2 experimental design (chronic×acute alcohol treatment×path blocked). The latent learning task had two phases: one, 30min long exploration trials (16 days, 1 trial/day) with left or right path of a complex maze blocked, and two, a subsequent probe trial with all paths open leading to a goal box that now contained stimulus fish. During the 16 days each fish received one of two chronic treatments: freshwater or 0.50% (v/v%) alcohol. Subsequently, fish were immersed for 1h in one of the following solutions: 0.00 (freshwater), 0.50% or 1.00% alcohol, the acute challenge. Behavior of fish was recorded during the probe trial that commenced immediately after the acute treatment. Path choices, latency to leave the start box and to enter the goal box, time spent in the goal box, distance traveled, and duration of freezing were quantified. We found that acute exposure to 1.00% alcohol after chronic freshwater disrupted learning performance, so did exposure to freshwater after chronic alcohol treatment (withdrawal). We also found exposure to chronic alcohol to diminish the effect of subsequent acute alcohol suggesting development of tolerance. Our results demonstrate that analysis of learning performance of zebrafish allows detection of alcohol-induced functional changes. The simplicity and scalability of the employed task also imply the utility of the zebrafish in high throughput drug screens. PMID:25557800

Luchiari, Ana C; Salajan, Diana C; Gerlai, Robert

2015-04-01

92

Alcohol and the Liver: Metabolism of Alcohol and Its Role in Hepatic and Extrahepatic Diseases  

Microsoft Academic Search

Dr. Charles S. Lieber has conducted clinical and experimental studies for more than four decades (three at Mount Sinai and the Bronx VA Medical Centers) with emphasis on liver, nutrition and GI pathophysiology. His major contributions include elucidation of the pathogenesis of alcoholic liver disease, by demonstrating the toxic role of alcohol and describing associated metabolic disor- ders. This was

CHARLES S. LIEBER

93

Acute hepatitis associated with clopidogrel: a case report and review of the literature.  

PubMed

Drug-induced hepatotoxicity is a common cause of acute hepatitis, and the recognition of the responsible drug may be difficult. We describe a case of clopidogrel-related acute hepatitis. The diagnosis is strongly suggested by an accurate medical history and liver biopsy. Reports about cases of hepatotoxicity due to clopidogrel are increasing in the last few years, after the increased use of this drug. In conclusion, we believe that physicians should carefully consider the risk of drug-induced hepatic injury when clopidogrel is prescribed. PMID:23846525

Pisapia, Raffaella; Abdeddaim, Amina; Mariano, Andrea; Rianda, Alessia; Vincenzi, Laura; Taibi, Chiara; Baiocchini, Andrea; Del Nonno, Franca; D?Offizi, Gianpiero

2015-01-01

94

Stent-Graft Treatment of Patients with Acute Bleeding from Hepatic Artery Branches  

SciTech Connect

Purpose. To present a new treatment option in patients with acute bleeding from the hepatic artery branches. Methods. Four male patients, 23-49 years old (mean 36.3 years), were treated for acute bleeding and subsequent transient hypotension. Bleeding episodes were secondary to hepatic artery pseudoaneurysms in two patients and surgical suture insufficiency in one patient. In the remaining patient, anastomotic leakage occurred following thrombolysis for hepatic artery thrombosis. Patients were treated by endovascular placement of one or two balloon-expandable stent-grafts, ranging from 17 to 28 mm in length. Results. All procedures were carried out without serious complications. All stent-grafts were deployed in the intended position with immediate cessation of bleeding and initial preservation of satisfactory blood flow. Conclusions. Bleeding from the hepatic artery can be treated by insertion of balloon-expandable stent-grafts in the acute setting.

Rami, Parag; Williams, David; Forauer, Andrew; Cwikiel, Wojciech [University of Michigan Hospital, Department of Radiology (United States)], E-mail: cwikiel@med.umich.edu

2005-04-15

95

Increased availability of central benzodiazepine receptors in patients with chronic hepatic encephalopathy and alcohol related cirrhosis  

PubMed Central

BACKGROUND/AIMS—To measure cerebral benzodiazepine receptor binding using 11C-flumazenil positron emission tomography in patients with stable chronic hepatic encephalopathy, who were also characterised by proton magnetic resonance spectroscopy.?METHODS—Six abstinent patients of mean age 61 years with alcohol related cirrhosis and grade I-II hepatic encephalopathy and 11 matched healthy volunteers were studied. Each patient's encephalopathy was defined according to clinical, psychometric, electroencephalographic, and magnetic resonance spectroscopy criteria. Using positron emission tomography, the brain volume of distribution of 11C-flumazenil was obtained; this reflects benzodiazepine receptor availability. Proton magnetic resonance spectra were acquired at 1.5 T using a multivoxel technique; peak area ratios were calculated for choline, glutamine/glutamate, N-acetylaspartate, and creatine resonances.?RESULTS—The mean volume of distribution of 11C-flumazenil was significantly higher in the cortex, cerebellum, and the basal ganglia in the patients compared with controls (p<0.001). In the patient group, the mean glutamine/glutamate to creatine ratio was significantly increased and the mean choline to creatine ratio was significantly decreased in all brain areas, compared with healthy volunteers. However, the N-acetylaspartate to creatine ratio was unchanged compared with controls.?CONCLUSIONS—The spectroscopy results reflect the cerebral metabolic derangement associated with hepatic encephalopathy. Stable grade I-II chronic hepatic encephalopathy in alcohol related cirrhosis may be associated with increased cerebral benzodiazepine receptor availability. However, a direct effect of previous chronic exposure to alcohol cannot be excluded.???Keywords: benzodiazepine receptors; chronic hepatic encephalopathy; 11C-flumazenil; in vivo proton magnetic resonance spectroscopy; positron emission tomography PMID:10716686

Jalan, R; Turjanski, N; Taylor-Robinson, S; Koepp, M; Richardson, M; Wilson, J; Bell, J; Brooks, D

2000-01-01

96

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

SciTech Connect

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.

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

97

Differences in Acute Response to Alcohol between African Americans and European Americans  

PubMed Central

Background Response to alcohol is a widely studied risk factor and potential endophenotype for alcohol use disorders. Research on African American response to alcohol has been limited despite large differences in alcohol use between African Americans and European Americans. Extending our previous work on the African American portion of this sample, the current study examined differences in acute subjective response to alcohol between African Americans and European Americans. Additionally, we tested if the association between response to alcohol and past month drinking behavior and alcohol-related problems differed across race. Methods One hundred and seventy eight participants (mean age = 21.87, SD = 1.23; 57% African American) who were moderate to heavy social drinkers completed an alcohol administration study in a laboratory setting, receiving a moderate dose of alcohol (0.72g/kg alcohol for males, 0.65g/kg for females). Acute alcohol response was measured at 8 time points (i.e., baseline, 15, 30, 45, 60, 90, 120, and 150 minutes). Results Latent growth curve models showed that African Americans experienced sharper increases in stimulation on the ascending limb compared to European Americans. African American women experienced sharper increases in sedation on the ascending limb compared to European American women. Change in sedation on the ascending limb was associated with past month drinking behavior. Stimulation on the ascending limb was related to alcohol-problems for African Americans but not European Americans. Conclusions We found differences in response to alcohol across racial groups: African Americans showed a stronger response to alcohol. Future studies are needed to incorporate response to alcohol into a larger model of African American alcohol use. PMID:23398190

Pedersen, Sarah L.; McCarthy, Denis M.

2013-01-01

98

Functional biomarkers for the acute effects of alcohol on the central nervous system in healthy volunteers  

PubMed Central

The central nervous system (CNS) effects of acute alcohol administration have been frequently assessed. Such studies often use a wide range of methods to study each of these effects. Unfortunately, the sensitivity of these tests has not completely been ascertained. A literature search was performed to recognize the most useful tests (or biomarkers) for identifying the acute CNS effects of alcohol in healthy volunteers. All tests were grouped in clusters and functional domains. Afterwards, the effect of alcohol administration on these tests was scored as improvement, impairment or as no effect. Furthermore, dose–response relationships were established. A total number of 218 studies, describing 342 different tests (or test variants) were evaluated. Alcohol affected a wide range of CNS domains. Divided attention, focused attention, visuo-motor control and scales of feeling high and of subjective drug effects were identified as the most sensitive functional biomarkers for the acute CNS effects of alcohol. The large number of CNS tests that are used to determine the effects of alcohol interferes with the identification of the most sensitive ones and of drug–response relationships. Our results may be helpful in selecting rational biomarkers for studies investigating the acute CNS effects of alcohol or for future alcohol- interaction studies. PMID:21284693

Zoethout, Remco W M; Delgado, Wilson L; Ippel, Annelies E; Dahan, Albert; van Gerven, Joop M A

2011-01-01

99

Changes in PTSD symptomatology during acute and protracted alcohol and cocaine abstinence  

Microsoft Academic Search

Previous research with substance users has demonstrated, across a variety of psychiatric disorders, significant decreases in psychological symptoms during early substance abstinence. To build on this literature, the current study prospectively assessed trauma symptomatology over 28 days during acute and protracted cocaine and alcohol abstinence. Participants were 162 male and female cocaine and\\/or alcohol dependent outpatients who reported a history

Scott F. Coffey; Julie A. Schumacher; Kathleen T. Brady; Bonnie Dansky Cotton

2007-01-01

100

New foe treated with old guns ¿ supportive role of steroids in the treatment of acute severe hepatitis E.  

PubMed

BackgroundAutochthonous hepatitis E has been observed with growing incidence in industrialized countries. Hepatitis E virus infection causes an acute hepatitis with spontaneous resolution in the majority of cases. However, in individual cases, hepatitis E may lead to life-threatening acute liver failure. In this report, we describe a case of acute liver injury caused by an autochthonous hepatitis E that resolved under steroid treatment. To our knowledge, this is the first case report describing supportive steroid monotherapy for acute liver injury due to hepatitis E.Case presentationA 63-year-old Caucasian male presented with acute liver injury of unknown origin. After excluding the most prevalent causes of acute liver injury, liver histology revealed signs of immune-mediated toxic or drug-induced liver injury. Therefore, immunosuppressive treatment with prednisolone was started. After initialization of steroid treatment, polymerase chain reaction analyses of peripheral blood and liver tissue revealed an acute hepatitis E virus infection (genotype 3). Under sustained steroid treatment, acute liver injury improved and hepatitis E infection resolved.ConclusionSteroid treatment might be an option to prevent progress of life-threatening liver failure and liver transplantation in patients with hepatitis E-induced acute liver injury and high-grade inflammation. PMID:25398314

Sebode, Marcial; Pischke, Sven; Lütgehetmann, Marc; Polywka, Susanne; Quaas, Alexander; Lohse, Ansgar W; Wege, Henning

2014-11-15

101

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

Microsoft Academic Search

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,

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

2012-01-01

102

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

Microsoft Academic Search

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,

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

2011-01-01

103

Hepatitis C Core Antigen Testing: A Reliable, Quick, and Potentially Cost-effective Alternative to Hepatitis C Polymerase Chain Reaction in Diagnosing Acute Hepatitis C Virus Infection.  

PubMed

Hepatitis C virus (HCV) is increasingly common among human immunodeficiency virus (HIV)-infected men who have sex with men. We evaluated the efficacy of HCV core antigen in diagnosing acute HCV in an HIV-infected cohort. Compared with HCV polymerase chain reaction, core antigen proved sensitive (100%) and specific (97.9%). As a quick, simple, and cost-effective test, it has considerable utility in screening for acute HCV. PMID:25301216

Cresswell, Fiona V; Fisher, Martin; Hughes, Daniel J; Shaw, Simon G; Homer, Gary; Hassan-Ibrahim, Mohammed O

2015-01-15

104

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

PubMed Central

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

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

2013-01-01

105

Psychosocial Correlates of Alcohol Use and Reduction for Individuals With Hepatitis C*  

PubMed Central

Objective: Patients with hepatitis C virus (HCV) are advised to refrain from alcohol consumption. A questionnaire was developed to measure concepts associated with alcohol use for individuals with HCV. Method: Subjects with HCV (N = 527) completed a telephone survey. Eligible respondents had screened negative for current abuse/dependence disorders (Alcohol Use Disorders Identification Test [AUDIT] ? 10). Measures of personality, self-efficacy, knowledge, readiness, coping styles, stigma, and symptoms were examined for associations with alcohol use. Results: Factor analysis supported a measurement structure of 105 items in 35 subdomains. A total of 26 subdomains had significant bivariate associations with alcohol use. Higher self-efficacy for resisting drinking in social situations was associated with lower alcohol use (r = ?.68, p < .001), as was knowledge of alcohol and HCV (r = ?.27, p < .001). Although agreeableness and marital status are typically associated with lower current drinking in samples of those with alcohol use problems, in our study agreeableness (?= .13, p < .01) and marital status (? = .08, p < .05) were modestly associated with higher current drinking. The final multivariate R2 was .55. Conclusions: The pattern of associations suggests the importance of the social aspects of drinking for drinking decisions. Existing brief interventions will need to be tailored to a contextualized psychosocial model for medical patients with HCV and AUDIT scores ? 10 to optimize effectiveness. Such future interventions should emphasize the potential medical hazards of drinking for persons with HCV, the maintenance of social relationships in the absence of alcohol use, and strategies for building confidence for resisting drinking in specific situations. PMID:21906506

Perzynski, Adam T.; Mccormick, Richard; Webster, Noah J.; Blixen, Carol E.; Kanuch, Stephanie; Thomas, Charles L.; Mullen, Kevin D.; Dawson, Neal V.

2011-01-01

106

Activation of brain NOP receptors attenuates acute and protracted alcohol withdrawal symptoms in the rat  

PubMed Central

BACKGROUND Alcohol withdrawal, refers to a cluster of symptoms that may occur from suddenly ceasing the use of alcohol after chronic or prolonged ingestion. These symptoms make alcohol abstinence difficult and increase the risk of relapse in recovering alcoholics. In previous studies, we demonstrated that treatment with N/OFQ significantly reduces alcohol consumption and attenuates alcohol-seeking behaviour induced by environmental conditioning factors or by stress in rats. In the present study we evaluated whether activation of brain NOP receptors may also attenuate alcohol withdrawal signs in rats. METHODS For this purpose animals were subjected to a 6 day chronic alcohol intoxication (by intragastric administration) and at 8, 10 and 12 hours following cessation of alcohol exposure they were treated intracerebroventricularly (ICV) with N/OFQ (0.0, 1.0 and 3.0 ?g/rat). Somatic withdrawal signs were scored after ICV treatment. In a subsequent experiment, to evaluate N/OFQ effects on alcohol withdrawal-induced anxiety another group of rats was subjected to ethanol intoxication and after one week was tested for anxiety behavior in the elevated plus maze (EPM). In the last experiment an additional group of rats was tested for anxiety elicited by acute ethanol intoxication (hangover anxiety). For this purpose, animals received an acute dose (3.0 g/kg) of 20% alcohol and 12-h later were tested in the EPM following ICV N/OFQ (0.0, 1.0 and 2.0?g/rat). RESULTS Results showed that N/OFQ significantly reduced the expression of somatic withdrawal signs and reversed anxiety-like behaviors associated with both chronic and acute alcohol intoxication. N/OFQ did not affect anxiety scores in nondependent animals. CONCLUSIONS The present findings suggest that the N/OFQ-NOP receptor system may represent a promising target for the development of new treatments to ameliorate alcohol withdrawal symptoms. PMID:21223310

Economidou, Daina; Cippitelli, Andrea; Stopponi, Serena; Braconi, Simone; Clementi, Stefano; Ubaldi, Massimo; Martin-Fardon, Rèmi; Weiss, Friedbert; Massi, Maurizio; Ciccocioppo, Roberto

2010-01-01

107

A Snapshot of the Hepatic Transcriptome: Ad Libitum Alcohol Intake Suppresses Expression of Cholesterol Synthesis Genes in Alcohol-Preferring (P) Rats  

PubMed Central

Research is uncovering the genetic and biochemical effects of consuming large quantities of alcohol. One prime example is the J- or U-shaped relationship between the levels of alcohol consumption and the risk of atherosclerotic cardiovascular disease. Moderate alcohol consumption in humans (about 30 g ethanol/d) is associated with reduced risk of coronary heart disease, while abstinence and heavier alcohol intake is linked to increased risk. However, the hepatic consequences of moderate alcohol drinking are largely unknown. Previous data from alcohol-preferring (P) rats showed that chronic consumption does not produce significant hepatic steatosis in this well-established model. Therefore, free-choice alcohol drinking in P rats may mimic low risk or nonhazardous drinking in humans, and chronic exposure in P animals can illuminate the molecular underpinnings of free-choice drinking in the liver. To address this gap, we captured the global, steady-state liver transcriptome following a 23 week free-choice, moderate alcohol consumption regimen (?7.43 g ethanol/kg/day) in inbred alcohol-preferring (iP10a) rats. Chronic consumption led to down-regulation of nine genes in the cholesterol biosynthesis pathway, including HMG-CoA reductase, the rate-limiting step for cholesterol synthesis. These findings corroborate our phenotypic analyses, which indicate that this paradigm produced animals whose hepatic triglyceride levels, cholesterol levels and liver histology were indistinguishable from controls. These findings explain, at least in part, the J- or U-shaped relationship between cardiovascular risk and alcohol intake, and provide outstanding candidates for future studies aimed at understanding the mechanisms that underlie the salutary cardiovascular benefits of chronic low risk and nonhazardous alcohol intake. PMID:25542004

Klein, Jonathon D.; Sherrill, Jeremy B.; Morello, Gabriella M.; San Miguel, Phillip J.; Ding, Zhenming; Liangpunsakul, Suthat; Liang, Tiebing; Muir, William M.; Lumeng, Lawrence; Lossie, Amy C.

2014-01-01

108

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

Microsoft Academic Search

  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

Ruth Weissenborn; Theodora Duka

2003-01-01

109

A case of heart failure due to alcoholic cardiomyopathy combined with acute pulmonary embolism  

PubMed Central

It has not been reported that cases of alcoholic cardiomyopathy (ACM) combined with acute pulmonary embolism (PE). We hereby present a case of a 48-year-old male with ACM with significant enlargement of the heart and heart failure is described. Then, the patient was seized with acute PE which was confirmed by specific examination and his symptoms. PMID:25276392

Xiao, Feng; Yuan, Wei; Li, Xiaorong; Wang, Gannan; Jiang, Ting; Wang, Weiwei; Zhang, Jinsong; Li, Ping; Qi, Lianwen

2014-01-01

110

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

E-print Network

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

Paris-Sud XI, Université de

111

Trends of Acute Hepatitis B Notification Rates in Eastern China from 2005 to 2013  

PubMed Central

Zhejiang Province was a high endemicity for hepatitis B disease in the 1990's. A number of measures implemented since then have begun to control and prevent hepatitis B. In 1992, hepatitis B vaccine came on the market. In 2002, hepatitis B vaccine was included in the national Expanded Programme on Immunization (EPI). Between 2007 and 2010, catch-up vaccination was implemented for children under 15. Since 2010, vaccination guidelines for high-risk groups have also been adopted. This study evaluated the impact of these control and prevention strategies on acute hepatitis B notification rates from 2005 through 2013. Data from the National Notifiable Disease Reporting System (NNDRS) revealed a steady downward trend in notification rates of acute hepatitis B. The most dramatic decline occurred among pre-adults, highlighting the benefits of EPI's policy of universal vaccination for children. However, the highest notification rates occurred among young adults of lower socio-economic status. These findings indicate the strong need to vaccinate young adults at risk for HBV infection as well as to collect risk-factor information in the NNDRS for monitoring and following up persons with acute hepatitis B. PMID:25504088

Wang, Zhifang; Chen, Yaping; Pan, Jinren

2014-01-01

112

EFFECTS OF LIGHT AND DARK BEERS ON HEPATIC CYTOCHROME P450 EXPRESSION IN MALE RATS RECEIVING ALCOHOLIC BEVERAGES AS PART OF TOTAL ENTERAL NUTRITION  

Technology Transfer Automated Retrieval System (TEKTRAN)

Background: Alcoholic beverages contain many congeners in addition to ethanol. Therefore, consumption of alcoholic beverages may have considerably different effects on expression of hepatic microsomal monooxygenases than the relatively selective induction of CYP2E1 observed following consumption of...

113

Effect of chronic administration of alcoholic beverages and seasoning containing alcohol on hepatic ethanol metabolism in mice.  

PubMed

Five-week-old male mice, C3H/HeNCrj (C3H/He), were given a 5% (v/v) ethanol solution, commercial alcoholic beverages (Japanese sake (sake) or red wine) or a Japanese seasoning (mirin [containing ethanol and a large amount of glucose]) ad libitum for 45 d, and were then examined for changes in the hepatic enzymes related to ethanol metabolism 2 h after oral administration of 5 g of ethanol/kg body weight. The specific activity of aniline hydroxylase (ANH) in the hepatic microsome increased significantly in all groups chronically administered ethanol solution, sake, red wine or mirin, and the greatest increase was in the hepatic microsome of mirin-administered mice. The cytochrome P-450 (CYP) 2E1 increased in the hepatic microsome of the mice administered ethanol solution, red wine or mirin where accompanied by high ANH activity. The immunoreactive band for CYP1A1 showed high specificity in the microsome of mice given sake, red wine or mirin. It was assumed that CYP1A1 was induced by unknown component(s) other than ethanol in these solutions. In the cytosolic fraction, following the chronic administration of sake and mirin, the total aldehyde dehydrogenase (A1DH) activity with high-Km decreased significantly. In the mitochondrial fraction, the activity of high-Km A1DH increased significantly in the mirin-administered mice which drank a large amount of ethanol, whereas that in the red wine-administered group tended to decrease. These results indicate that the enzyme activities related to the oxidation of both ethanol and acetaldehyde in the cytosolic, mitochondrial and microsomal fractions of the liver were affected by either the action of ethanol or its interaction with other constituents of sake, red wine and mirin. PMID:9530614

Kishimoto, R; Ueda, M; Kawakami, M; Goda, K; Park, S S; Nakata, Y

1997-12-01

114

Effect of chronic alcohol consumption on Hepatic SIRT1 and PGC-1{alpha} in rats  

SciTech Connect

The nuclear genes, NAD-dependent deacetylase Sirtuis 1 (SIRT1) and the peroxisome proliferator-activated receptor-{gamma} coactivator1{alpha} (PGC-1{alpha}) are regulators of energy metabolism. Here, we studied the role of alcohol consumption in expression of these sensing molecules. Alcohol significantly reduced hepatic SIRT1 mRNA by 50% and PGC-1{alpha} mRNA by 46% and it significantly inhibited the protein expression of SIRT1 and PGC-1{alpha}, while the transcription factor PPAR-{gamma} remained unchanged. However, when the lipid composition of the alcohol diet was changed by replacing long-chain triglycerides (LCT) with medium chain triglycerides (MCT), SIRT1 and PGC-1{alpha} mRNA were restored to near control levels. This study demonstrates that alcohol reduces key energy sensing proteins and that replacement of LCT by MCT affects the transcription of these genes. Since there is a pathophysiological link between SIRT1 and PGC-1{alpha} and mitochondrial energy, the implication of the study is that mitochondrial dysfunction due to alcohol abuse can be treated by dietary modifications.

Lieber, Charles S. [Section of Liver Diseases, James J. Peters VA Medical Center, 130 West Kingsbridge Road (151-2), Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY (United States)], E-mail: liebercs@aol.com; Leo, Maria A. [Section of Liver Diseases, James J. Peters VA Medical Center, 130 West Kingsbridge Road (151-2), Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY (United States); Wang Xiaolei [Department of Medicine, Mount Sinai School of Medicine, New York, NY (United States); DeCarli, Leonore M. [Section of Liver Diseases, James J. Peters VA Medical Center, 130 West Kingsbridge Road (151-2), Bronx, NY 10468 (United States)

2008-05-23

115

Acute and Chronic Effects of Alcohol on Trail Making Test Performance Among Underage Drinkers in a Field Setting  

PubMed Central

Objective: Alcohol’s effects on executive functioning are well documented. Research in this area has provided much information on both the acute and chronic effects of alcohol on processes such as working memory and mental flexibility. However, most research on the acute effects of alcohol is conducted with individuals older than 21 years of age. Using field recruitment methods can provide unique empirical data on the acute effects of alcohol on an underage population. Method: The current study examined the independent effects of acute alcohol intoxication (measured by breath alcohol content) and chronic alcohol use (measured by years drinking) on a test of visuomotor performance and mental flexibility (Trail Making Test) among 91 drinkers ages 18–20 years recruited from a field setting. Results: Results show that breath alcohol predicts performance on Trails B, but not on Trails A, and that years drinking, above and beyond acute intoxication, predicts poorer performance on both Trails A and B. Conclusions: These data suggest that, independent of the acute effects of alcohol, chronic alcohol consumption has deleterious effects on executive functioning processes among underage drinkers. Our discussion focuses on the importance of these data in describing the effect of alcohol on adolescents and the potential for engaging in risky behavior while intoxicated. PMID:23739029

Day, Anne M.; Lisman, Stephen A.; Johansen, Gerard E.; Spear, Linda P.

2013-01-01

116

[Imported acute hepatitis in Spanish travelers to tropical countries].  

PubMed

Among the immunizable diseases, viral hepatitis is the most frequently diagnosed in travellers. The epidemiology and the clinical presentation of the imported viral hepatitis among patients in the Tropical Medicine Unit of Hospital Clínic (Barcelona) are studied in this article. A retrospective review of 47 viral hepatitis in Spanish travellers seen during the period 1988-1991 is presented, representing 2.47% of all diagnosis. Only a third of the patients were hepatitis A cases. The duration of the trip was significantly shorter in those who acquired hepatitis of the A and non-A--non-B types. Africa (60% cases), India and South East Asia (17%) and Central America (16%) were considered areas of risk. The B, C and non-A--non-B hepatitis types had a more silent clinical and biological presentation. Gathered data confirm the importance of hepatitis as an imported disease, the partial protection of the Spanish population against hepatitis A and the need to introduce this infection among the advice to be given in a travellers clinic. PMID:7938838

García, F; Gascón, J; Ruiz, L; Gómez-Olivé, X; Corachán, M

1994-08-01

117

Sleep disturbances after acute exposure to alcohol in mothers’ milk  

Microsoft Academic Search

The results of previous research in our laboratory revealed that breast-fed infants experience significantly less active sleep after exposure to alcohol in their mothers’ milk than do breast-fed infants not exposed to alcohol. The present study tested the hypothesis that infants would compensate for such reductions if their mothers then refrained from drinking alcohol. To this end, 23 breast-fed infants

Julie A. Mennella; Pamela L. Garcia-Gomez

2001-01-01

118

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

PubMed

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

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

2003-01-01

119

Gene Expression Profiles of T Cells from Hepatitis E Virus Infected Patients in Acute and Resolving Phase  

Microsoft Academic Search

Background and Aims  Approximately 50% of acute viral hepatitis in young adults and in pregnant women is due to hepatitis E virus (HEV) infection\\u000a in developing countries. T cell-mediated immune injury probably plays a key role in the pathogenesis of acute hepatitis illness.\\u000a However, there is a paucity of data on the global gene expression programs activated on T cells, which

Nirupma TrehanPati; Sukriti Sukriti; Robert Geffers; Syed Hissar; Peggy Riese; Tanja Toepfer; Carlos A. Guzman; Shiv Kumar Sarin

120

Ferritin L and Ferritin H are differentially located within hepatic and extra hepatic organs under physiological and acute phase conditions.  

PubMed

Ferritin L (FTL) and Ferritin H (FTH) subunits are responsible for intercellular iron storage. We previously reported increasing amounts of liver cytoplasmic and nuclear iron content during acute phase response (APR). Aim of the present study is to demonstrate intracellular localization of ferritin subunits in liver compared with extra hepatic organs of rat under physiological and acute phase conditions. Rats were administered turpentine-oil (TO) intramuscularly to induce a sterile abscess (acute-phase-model) and sacrificed at different time points. Immunohistochemistry was performed utilizing horse-reddish-peroxidise conjugated secondary antibody on 4?m thick section. Liver cytoplasmic and nuclear protein were used for Western blot analysis. By means of immunohistology, FTL was detected in cytoplasm while a strong nuclear positivity for FTH was evident in the liver. Similarly, in heart, spleen and brain FTL was detected mainly in the cytoplasm while FTH demonstrated intense nuclear and a weak cytoplasmic expression. Western blot analysis of cytoplasmic and nuclear fractions from liver, heart, spleen and brain further confirmed mainly cytoplasmic expression of FTL in contrast to the nuclear and cytoplasmic expression of FTH. The data presented demonstrate the differential localization of FTL and FTH within hepatic and extra hepatic organs being FTL predominantly in the cytoplasm while FTH predominantly in nucleus. PMID:23573308

Ahmad, Shakil; Moriconi, Federico; Naz, Naila; Sultan, Sadaf; Sheikh, Nadeem; Ramadori, Giuliano; Malik, Ihtzaz Ahmed

2013-01-01

121

Ferritin L and ferritin H are differentially located within hepatic and extra hepatic organs under physiological and acute phase conditions  

PubMed Central

Ferritin L (FTL) and Ferritin H (FTH) subunits are responsible for intercellular iron storage. We previously reported increasing amounts of liver cytoplasmic and nuclear iron content during acute phase response (APR). Aim of the present study is to demonstrate intracellular localization of ferritin subunits in liver compared with extra hepatic organs of rat under physiological and acute phase conditions. Rats were administered turpentine-oil (TO) intramuscularly to induce a sterile abscess (acute-phase-model) and sacrificed at different time points. Immunohistochemistry was performed utilizing horse-reddish-peroxidise conjugated secondary antibody on 4?m thick section. Liver cytoplasmic and nuclear protein were used for Western blot analysis. By means of immunohistology, FTL was detected in cytoplasm while a strong nuclear positivity for FTH was evident in the liver. Similarly, in heart, spleen and brain FTL was detected mainly in the cytoplasm while FTH demonstrated intense nuclear and a weak cytoplasmic expression. Western blot analysis of cytoplasmic and nuclear fractions from liver, heart, spleen and brain further confirmed mainly cytoplasmic expression of FTL in contrast to the nuclear and cytoplasmic expression of FTH. The data presented demonstrate the differential localization of FTL and FTH within hepatic and extra hepatic organs being FTL predominantly in the cytoplasm while FTH predominantly in nucleus. PMID:23573308

Ahmad, Shakil; Moriconi, Federico; Naz, Naila; Sultan, Sadaf; Sheikh, Nadeem; Ramadori, Giuliano; Malik, Ihtzaz Ahmed

2013-01-01

122

Impact of hepatitis C virus infection on the risk of death of alcohol-dependent patients.  

PubMed

Hepatitis C virus (HCV) infection is frequent among patients with alcohol use disorders. We aimed to analyse the impact of HCV infection on survival of patients seeking treatment for alcohol use. This was a longitudinal study in a cohort of patients who abused alcohol recruited in two detoxification units. Socio-demographic and alcohol use characteristics, liver function tests for the assessment of alcohol-related liver disease and HCV and HIV infection serologies were obtained at admission. Patients were followed until December 2008; causes of death were ascertained through clinical records and death registry. Cox models were used to analyse predictors of death. A total of 675 patients (79.7% men) were admitted; age at admission was 43.5 years (IQR: 37.9-50.2 years), duration of alcohol abuse was 18 years (IQR: 11-24 years), and median alcohol consumption was 200 g/day (IQR: 120-275 g/day). Distribution of patients according to viral infections was as follows: 75.7% without HCV or HIV infection, 14.7% HCV infection alone and 8.1% HCV/HIV coinfection. Median follow-up was 3.1 years (IQR: 1.5-5.1 years) accounting for 2,345 person-years. At the end of study, 78 patients (11.4%) had died. In the multivariate analysis, age at admission (HR = 1.71, 95%CI: 1.05-2.80), alcohol-related liver disease (HR = 3.55, 95%CI: 1.93-6.53) and HCV/HIV co-infection (HR = 3.86 95%CI: 2.10-7.11) were predictors of death. Younger patients (?43 years) with HCV infection were more likely to die than those without viral infections (HR = 3.1, 95%CI: 1.3-7.3; P = 0.007). Among patients with alcohol-related liver disease, mortality rate was high, irrespective of viral infections. These data show that HCV infection confers a worse prognosis in patients with alcohol use disorders. PMID:25131721

Fuster, D; Sanvisens, A; Bolao, F; Serra, I; Rivas, I; Tor, J; Muga, R

2015-01-01

123

The acute effects of alcohol on auditory thresholds  

Microsoft Academic Search

BACKGROUND: There is very little knowledge about alcohol-induced hearing loss. Alcohol consumption and tolerance to loud noise is a well observed phenomenon as seen in the Western world where parties get noisier by the hour as the evening matures. This leads to increase in the referrals to the \\

Tahwinder Upile; Fabian Sipaul; Waseem Jerjes; Sandeep Singh; Seyed Ahmad Reza Nouraei; Mohammed El Maaytah; Peter Andrews; John Graham; Colin Hopper; Anthony Wright

2007-01-01

124

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

PubMed Central

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

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

2014-01-01

125

Acute Alcohol Effects on Contextual Memory BOLD Response: Differences Based on Fragmentary Blackout History  

PubMed Central

Background Contextual memory, or memory for source details, is an important aspect of episodic memory and has been implicated in alcohol-induced fragmentary blackouts (FB). Little is known, however, about how neural functioning during contextual memory processes may differ between individuals with and without a history of fragmentary blackouts. This study examined whether neural activation during a contextual memory task differed by history of fragmentary blackout and acute alcohol consumption. Methods Twenty-four matched individuals with (FB+; n = 12) and without (FB?; n = 12) a history of FBs were recruited from a longitudinal study of alcohol use and behavioral risks and completed a laboratory beverage challenge followed by two functional magnetic resonance imaging (fMRI) sessions under no alcohol and alcohol [breath alcohol concentration (BrAC) = 0.08%] conditions. Task performance and brain hemodynamic activity during a block design contextual memory task were examined across 48 fMRI sessions. Results Groups demonstrated no differences in performance on the contextual memory task, yet exhibited different brain response patterns after alcohol intoxication. A significant FB group by beverage interaction emerged in bilateral dorsolateral prefrontal cortex and posterior parietal cortex with FB? individuals showing greater BOLD response after alcohol exposure (p < .05). Conclusions Alcohol had differential effects on neural activity for FB+ and FB? individuals during recollection of contextual information, perhaps suggesting a neurobiological mechanism associated with alcohol-induced fragmentary blackouts. PMID:22420742

Wetherill, Reagan R.; Schnyer, David M.; Fromme, Kim

2011-01-01

126

Neostigmine for the treatment of acute hepatic encephalopathy with acute intestinal pseudo-obstruction in a cirrhotic patient.  

PubMed

We treated a 49-yr-old man with neostigmine, who had liver cirrhosis, acute hepatic encephalopathy, and acute intestinal pseudoobstruction. He was admitted in a state of hepatic confusion. On physical examination, the abdomen was distended; and bowel sound was absent. Plain abdomen film revealed multiple air-fluid levels and distention of bowel loops. Initially, we gave him lactulose enemas every 6 hr for one day without improvement in his mental state. Furthermore, he became to a state of coma. Therefore, we gave him 0.5 mg of neostigmine subcutaneously to improve his peristaltic movement, and 2 L of polyethylene glycol electrolyte solution through a nasogastric tube for 4 hr to reduce the production and absorption of gut-derived toxins of nitrogenous compounds. After these treatments, the venous ammonia level decreased to the normal range within 12 hr, and the coma disappeared after 2 days. We suggest that neostigmine may be one of the most effective treatments to initiate peristaltic movement and bowel cleansing in cirrhotic patients with acute hepatic encephalopathy and acute intestinal pseudoobstruction. PMID:15716622

Park, Chang Hwan; Joo, Young Eun; Kim, Hyun Soo; Choi, Sung Kyu; Rew, Jong Sun; Kim, Sei Jong

2005-02-01

127

Acute hepatitis in three patients with systemic juvenile idiopathic arthritis taking interleukin-1 receptor antagonist  

PubMed Central

Purpose We investigated the etiology of acute hepatitis in three children with systemic Juvenile Idiopathic Arthritis (sJIA) taking Interleukin-1 receptor antagonist (IL1RA). Methods Laboratory and clinical data for three children with sJIA diagnosed at ages 13 months to 8 years who developed acute hepatitis during treatment with IL1RA were reviewed for evidence of sJIA flare, infection, macrophage activation syndrome (MAS), malignancy, and drug reaction. Results In all patients, hepatitis persisted despite cessation of known hepatotoxic drugs and in absence of known infectious triggers, until discontinuation of IL1RA. Liver biopsies had mixed inflammatory infiltrates with associated hepatocellular injury suggestive of an exogenous trigger. At the time of hepatitis, laboratory data and liver biopsies were not characteristic of MAS. In two patients, transaminitis resolved within one week of discontinuing IL1RA, the third improved dramatically in one month. Conclusions Although sJIA symptoms improved significantly on IL1RA, it appeared that IL1RA contributed to the development of acute hepatitis. Hepatitis possibly occurred as a result of an altered immune response to a typical childhood infection while on IL1RA. Alternatively, hepatitis could have represented an atypical presentation of MAS in patients with sJIA taking IL1RA. Further investigation is warranted to determine how anti-IL1 therapies alter immune responsiveness to exogenous triggers in patients with immune dysfunction such as sJIA. Our patients suggest that close monitoring for hepatic and other toxicities is indicated when treating with IL1RA. PMID:20028520

2009-01-01

128

Kudzu Extract Treatment Does Not Increase the Intoxicating Effects of Acute Alcohol in Human Volunteers  

PubMed Central

Background Isoflavone administration in the form of a purified extract from the herbal medication kudzu root has been shown to reduce, but not eliminate, alcohol consumption in alcohol-abusing and alcohol-dependent men. The precise mechanism of this action is unknown, but one possible explanation for these results is that the isoflavones in kudzu might actually increase the intensity or duration of alcohol’s effects and thus delay the desire for subsequent drinks. The present study was designed to test this hypothesis. Methods Twelve (12) healthy adult men and women (27.5±1.89 yrs old) who consumed moderate amounts of alcohol (7.8±0.63 drinks/week) participated in a double-blind, placebo-controlled crossover study in which they were treated with either kudzu extract (total isoflavone dose of 750 mg/day) or matched placebo for nine days. On days 8 and 9, participants received an acute challenge of ethyl alcohol (either 0.35 or 0.7 g/kg alcohol). During the challenges the following measures were collected: subjective effects, psychomotor (body sway), cognitive performance (vigilance/reaction time), physiological measures (heart rate and skin temperature), and plasma ethanol concentration. Results Alcohol resulted in a dose-related alteration in subjective measures of intoxication, impairment of stance stability, and vigilance/reaction time. Kudzu extract did not alter participants’ subjective responses to the alcohol challenge or to alcohol’s effects on stance stability or vigilance/reaction time. However, individuals treated with kudzu extract experienced a slightly more rapid rise in plasma ethanol levels, but only after the 0.7 g/kg dose. This transient effect during the first 30 minutes of the ascending plasma alcohol curve lasted only 10-15 minutes; there were no differences in peak plasma alcohol levels or alcohol elimination kinetics. Additionally, kudzu pretreatment enhanced the effects of the 0.7 g/kg dose of alcohol on heart rate and skin temperature. Conclusions These data suggest that individuals who drink alcohol while being treated with kudzu extract experience no adverse consequences and further, the reported reductions in alcohol intake after kudzu extract treatment are not related to an alteration in alcohol’s subjective or psychomotor effects. PMID:21244439

Penetar, David M.; MacLean, Robert R.; McNeil, Jane F.; Lukas, Scott E.

2010-01-01

129

Pancreatic Damage after the First Episode of Acute Alcoholic Pancreatitis and Its Association with the Later Recurrence Rate  

Microsoft Academic Search

Background: Acute alcoholic pancreatitis (AAP) recurs in up to half of the patients, continuous alcohol consumption being an important risk factor. Changes in pancreatic function and morphology after acute pancreatitis have been characterized previously, but their association with later recurrences has not been adequately studied. Patients and Methods: In this prospective follow-up study, the pancreatic function of 54 patients (47

Hanna Pelli; Riitta Lappalainen-Lehto; Anneli Piironen; Satu Järvinen; Juhani Sand; Isto Nordback

2009-01-01

130

Acute Sterol O-Acyltransferase 2 (SOAT2) Knockdown Rapidly Mobilizes Hepatic Cholesterol for Fecal Excretion  

PubMed Central

The primary risk factor for atherosclerotic cardiovascular disease is LDL cholesterol, which can be reduced by increasing cholesterol excretion from the body. Fecal cholesterol excretion can be driven by a hepatobiliary as well as a non-biliary pathway known as transintestinal cholesterol efflux (TICE). We previously showed that chronic knockdown of the hepatic cholesterol esterifying enzyme sterol O-acyltransferase 2 (SOAT2) increased fecal cholesterol loss via TICE. To elucidate the initial events that stimulate TICE, C57Bl/6 mice were fed a high cholesterol diet to induce hepatic cholesterol accumulation and were then treated for 1 or 2 weeks with an antisense oligonucleotide targeting SOAT2. Within 2 weeks of hepatic SOAT2 knockdown (SOAT2HKD), the concentration of cholesteryl ester in the liver was reduced by 70% without a reciprocal increase in hepatic free cholesterol. The rapid mobilization of hepatic cholesterol stores resulted in a ?2-fold increase in fecal neutral sterol loss but no change in biliary cholesterol concentration. Acute SOAT2HKD increased plasma cholesterol carried primarily in lipoproteins enriched in apoB and apoE. Collectively, our data suggest that acutely reducing SOAT2 causes hepatic cholesterol to be swiftly mobilized and packaged onto nascent lipoproteins that feed cholesterol into the TICE pathway for fecal excretion. PMID:24901470

Marshall, Stephanie M.; Gromovsky, Anthony D.; Kelley, Kathryn L.; Davis, Matthew A.; Wilson, Martha D.; Lee, Richard G.; Crooke, Rosanne M.; Graham, Mark J.; Rudel, Lawrence L.

2014-01-01

131

Evaluation of a new rapid immunochromatographic assay for serodiagnosis of acute hepatitis E infection.  

PubMed

A rapid and reliable diagnostic assay for acute hepatitis E virus (HEV) infection is needed. We evaluated a rapid, immunochromatographic assay for IgM antibodies to HEV (ASSURE HEV IgM Rapid Test) using acute-phase HEV samples (n = 200) from Indonesia and Nepal and convalescent-phase HEV samples (n = 70) from Nepal. Blood donors in Thailand (n = 100), individuals with hepatitis A (n = 80), hepatitis B (n = 45), and hepatitis C (n = 50) in Thailand and Nepal, acute-phase sera of individuals with Epstein-Barr virus infection (n = 20), and rheumatoid factor-positive blood (n = 26) served as negative controls. The assay had a sensitivity of 93% (95% confidence interval [CI] = 88.5-96.1%) and a specificity of 99.7% (95% CI = 98.3-100%). The positive and negative predictive values were 99.5% (95% CI = 97.1-100%) and 95.8% (95% CI = 93.1-97.7%), respectively. These results suggest that this assay is a sensitive and specific tool for the rapid diagnosis of acute HEV infection. PMID:16282308

Myint, Khin S A; Guan, Ming; Chen, Hsiao Ying; Lu, Yang; Anderson, David; Howard, Teresa; Noedl, Harald; Mammen, Mammen P

2005-11-01

132

Adolescents and Alcohol: Acute Sensitivities, Enhanced Intake, and Later Consequences*  

PubMed Central

Adolescence is an evolutionarily conserved developmental period characterized by notable maturational changes in brain along with various age-related behavioral characteristics, including the propensity to initiate alcohol and other drug use and consume more alcohol per occasion than adults. After a brief review of adolescent neurobehavioral function from an evolutionary perspective, the paper will turn to assessment of adolescent alcohol sensitivity and consequences, with a focus on work from our laboratory. After summarizing evidence showing that adolescents differ considerably from adults in their sensitivity to various effects of alcohol, potential contributors to these age-typical sensitivities will be discussed, and the degree to which these findings are generalizable to other drugs and to human adolescents will be considered. Recent studies are then reviewed to illustrate that repeated alcohol exposure during adolescence induces behavioral, cognitive, and neural alterations that are highly specific, replicable, persistent and dependent on the timing of the exposure. Research in this area is in its early stages, however, and more work will be necessary to characterize the extent of these neurobehavioral alterations and further determine the degree to which observed effects are specific to alcohol exposure during adolescence. PMID:24291291

Spear, Linda Patia

2014-01-01

133

[Study of lymphocyte subpopulations by means of monoclonal antibodies in acute hepatitis A and B].  

PubMed

We studied T3, T4 and T8 lymphocyte populations in peripheral blood by monoclonal antibodies in 40 patients with acute viral hepatitis (Type A 20; Type B 20) who underwent outcome to complete recovery. We compared the results with 20 healthy subjects (control group). We found a decrease in total lymphocytes measured by T3 monoclonal antibodies and a significant increase in T8 lymphocyte populations compared with control groups. In the early stage the T4/T8 ratio was decreased. Lymphocyte populations and T4/T8 ratio was normal in 3-6 month follow-up for the acute A hepatitis group and 3.6 month to a year follow-up for the B hepatitis group. Results were related to the humoral and clinical outcome. PMID:2616985

Collazo, L; Sotto, A; Morales, M G; Borbolla, E

1989-01-01

134

Hodgkin’s lymphoma coexisting with liver failure secondary to acute on chronic hepatitis B  

PubMed Central

Acute on chronic liver failure (ACLF) is rarely the initial manifestation of a malignant process or precipitated by the initiation of anti-viral treatment with a nucleoside or nucleotide agent. We report an unusual case of ACLF temporally associated with initiation of Entecavir for treatment of chronic hepatitis B. Early Hodgkin’s lymphoma (HL) was unmasked with initiation of the anti-viral treatment which may have exacerbated ACLF. To the best of our knowledge, this has not been described in the literature. In reviewing our patients clinical course and liver autopsy, he developed a severe acute exacerbation of his chronic hepatitis B virus coinciding with the institution of antiviral therapy and the underlying HL perhaps modulating the overall degree of hepatic injury. PMID:24303460

Palta, Renee; McClune, Amy; Esrason, Karl

2013-01-01

135

Animated bird silhouette above the tank: Acute alcohol diminishes fear responses in zebrafish  

PubMed Central

Alcohol dependence and alcohol abuse represent major unmet medical needs. The zebrafish is considered to be a promising vertebrate species with which the effects of alcohol on brain function and behavior and the mechanisms underlying these effects may be studied. Alcohol is known to induce alterations in motor function as well as fear and anxiety. Here we present a recently developed fear paradigm in which we employ an animated (moving) image of a bird silhouette. We measure the effect of acute alcohol administration (dose range employed: 0.00 – 0.75 vol/vol percentage, bath exposure for 60 minutes) on the behavioral responses of zebrafish. We test these responses during a pre-stimulus, stimulus and post-stimulus period of the task using both a video-tracking and an observation based quantification method. The fear inducing stimulus was found to decrease the distance of the zebrafish from the bottom of the tank, to increase number of erratic movements, and to increase the number of jumps in alcohol exposed fish (versus control fish). Alcohol attenuated these fear responses in a dose dependent manner. In addition, alcohol decreased general activity at the highest dose, an effect that was independent of the presentation of the stimulus. We discuss the similarities and differences between observation and video-tracking based results and conclude that fear paradigms will be useful in revealing alcohol induced functional changes in the brain of zebrafish. PMID:22266470

Luca, Ruxandra M.; Gerlai, Robert

2012-01-01

136

RNAi-mediated silencing of hepatic Alas1 effectively prevents and treats the induced acute attacks in acute intermittent porphyria mice  

PubMed Central

The acute hepatic porphyrias are inherited disorders of heme biosynthesis characterized by life-threatening acute neurovisceral attacks. Factors that induce the expression of hepatic 5-aminolevulinic acid synthase 1 (ALAS1) result in the accumulation of the neurotoxic porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG), which recent studies indicate are primarily responsible for the acute attacks. Current treatment of these attacks involves i.v. administration of hemin, but a faster-acting, more effective, and safer therapy is needed. Here, we describe preclinical studies of liver-directed small interfering RNAs (siRNAs) targeting Alas1 (Alas1-siRNAs) in a mouse model of acute intermittent porphyria, the most common acute hepatic porphyria. A single i.v. dose of Alas1-siRNA prevented the phenobarbital-induced biochemical acute attacks for approximately 2 wk. Injection of Alas1-siRNA during an induced acute attack significantly decreased plasma ALA and PBG levels within 8 h, more rapidly and effectively than a single hemin infusion. Alas1-siRNA was well tolerated and a therapeutic dose did not cause hepatic heme deficiency. These studies provide proof-of-concept for the clinical development of RNA interference therapy for the prevention and treatment of the acute attacks of the acute hepatic porphyrias. PMID:24821812

Yasuda, Makiko; Gan, Lin; Chen, Brenden; Kadirvel, Senkottuvelan; Yu, Chunli; Phillips, John D.; New, Maria I.; Liebow, Abigail; Fitzgerald, Kevin; Querbes, William; Desnick, Robert J.

2014-01-01

137

Alcoholic pancreatitis: mechanisms of viral infections as cofactors in the development of acute and chronic pancreatitis and fibrosis  

Microsoft Academic Search

Acute and chronic pancreatitis is asso- ciated with alcohol abuse, but symptomatic pancre- atitis develops in only a small proportion of persons (10-20%) who abuse alcohol. This apparent par- adox has led to the notion that additional cofactors are involved in the development of alcoholic pan- creatitis. Potential cofactors, such as diet and smoking, have been suggested, but there are

Thomas R. Jerrells; Debbie Vidlak; Jennifer M. Strachota

2007-01-01

138

Hepatitis B and Hepatitis C in Pregnancy  

MedlinePLUS

... sometimes causes no signs or symptoms. How is hepatitis B virus infection spread? Hepatitis B virus is spread by ... and hepatitis C infections during pregnancy? • How is hepatitis B virus infection spread? • What is acute hepatitis B virus ...

139

[Study of lymphocyte subpopulations with monoclonal antibodies in acute hepatitis A and B].  

PubMed

Using monoclonal antibodies, it was determined the T3, T4 and T8 1ym phocyte populations in the blood samples of 40 patients with acute viral hepatitis (20 type A and 20 type B). al patients showed complete remission from it. The results of this study were compared with those of a control group of 20 healthy subjects. There was a non significant decreased of the total number of lymphocytes measured with the T3 monoclonal antibody in both types of hepatitis. The number of T8 lymphocytes was significantly increased (p less than 0.05) when the results were compared with those of the control group. The quotient T4/T8 was diminished in the initial phase of the disease (p less than 0.05). There were no other differences between hepatitis A and hepatitis B. In the follow up of the disease, the results tend to normal values in the whole group of patients. PMID:1840845

Collazo, L; Sotto, A; Morales, M G; Borbolla, E

1991-01-01

140

Differential gene expression profiles in acute hepatic failure model in mice infected with MHV3 virus intervened by anti-hepatic failure compound  

Microsoft Academic Search

Summary  Differential gene expression profiles in Balb\\/cJ mouse model of acute hepatic failure infected with MHV-3 virus intervened\\u000a by anti-hepatic failure compound (AHFC) and the changes of cytokines regulated by genes were investigated. The Balb\\/cj mice\\u000a were divided into AHFC-intervened group and control group randomly. Acute hepatic failure model of Balb\\/cJ mice infected with\\u000a MHV-3 virus was established. The survival rate

Jiaquan Huang; Fei Xiao; Haijing Yu; Tiejun Huang; Haiyan Huang; Qin Ning

2007-01-01

141

MnSOD Overexpression Prevents Liver Mitochondrial DNA Depletion after an Alcohol Binge but Worsens This Effect after Prolonged Alcohol Consumption in Mice  

Microsoft Academic Search

Both acute and chronic alcohol consumption increase reactive oxygen species (ROS) formation and lipid peroxidation, whose products damage hepatic mitochondrial DNA (mtDNA). To test whether manganese superoxide dismutase (MnSOD) overexpression modulates acute and chronic alcohol-induced mtDNA lesions, transgenic MnSOD-overexpressing (TgMnSOD+++) mice and wild-type (WT) mice were treated by alcohol, either chronically (7 weeks in drinking water) or acutely (single intragastric

Abdellah Mansouri; Arige Tarhuni; Isabelle Larosche; Florence Reyl-Desmars; Christine Demeilliers; Françoise Degoul; Pierre Nahon; Angela Sutton; Richard Moreau; Bernard Fromenty; Dominique Pessayre

2010-01-01

142

Effect of Indigofera tinctoria Linn on liver antioxidant defense system during D-galactosamine/endotoxin-induced acute hepatitis in rodents.  

PubMed

Effects of pre-treatment with the alcoholic extract of I. tinctoria (500 mg/kg body wt/day, p.o. for 21 days) on liver antioxidant defense system during acute hepatitis induced by D-galactosamine (D-GalN)/endotoxin (LPS extracted by phenol water method from E. coli serotype 0111.B4; 300 mg and 30 micrograms/kg body wt/day, i.p., 18 hr before the assay) were investigated on the activities of enzymic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase and glutathione-s-transferase, and levels of total reduced glutathione in the liver of normal and experimental groups of male albino rats. Since lipid peroxidation and associated membrane damage is a key feature of D-galN/LPS-induced liver injury, the levels of lipid peroxides, was estimated and used as an index of oxidative stress. D-GalN/endotoxin-induced hepatic damage was manifested by a significant decrease in the activities of antioxidant enzymes, decreased glutathione levels and increased levels of lipid peroxides. I. tinctoria pre-treated rats showed considerable protection against D-galN/endotoxin, induced oxidative stress as evidenced by a significant increase in the activities of all the antioxidant enzymes studied and significant decrease in the levels of lipid peroxides. Results indicate that pretreatment with I. tinctoria extract in rats is very effective in reducing D-GalN/endotoxin-induced oxidative stress suggesting an antioxidant effect. PMID:11480218

Sreepriya, M; Devaki, T; Balakrishna, K; Apparanantham, T

2001-02-01

143

Acute toxic hepatitis caused by an aloe vera preparation in a young patient: a case report with a literature review.  

PubMed

Aloe is one of the leading products used in phytomedicine. Several cases of aloe-induced toxic hepatitis have been reported in recent years. However, its toxicology has not yet been systematically described in the literature. A 21-year-old female patient was admitted to our hospital with acute hepatitis after taking an aloe vera preparation for four weeks. Her history, clinical manifestation, laboratory findings, and histological findings all led to the diagnosis of aloe vera-induced toxic hepatitis. We report herein on a case of acute toxic hepatitis induced by aloe vera. PMID:25073673

Lee, Jeonghun; Lee, Mi Sun; Nam, Kwan Woo

2014-07-01

144

Alcohol-induced defects in hepatic transcytosis may be explained by impaired dynein function.  

PubMed

Alcoholic liver disease has been clinically well described, but the molecular mechanisms leading to hepatotoxicity have not been fully elucidated. Previously, we determined that microtubules are hyperacetylated and more stable in ethanol-treated WIF-B cells, VL-17A cells, liver slices, and in livers from ethanol-fed rats. From our recent studies, we believe that these modifications can explain alcohol-induced defects in microtubule motor-dependent protein trafficking including nuclear translocation of a subset of transcription factors. Since cytoplasmic dynein/dynactin is known to mediate both microtubule-dependent translocation and basolateral to apical/canalicular transcytosis, we predicted that transcytosis is impaired in ethanol-treated hepatic cells. We monitored transcytosis of three classes of newly synthesized canalicular proteins in polarized, hepatic WIF-B cells, an emerging model system for the study of liver disease. As predicted, canalicular delivery of all proteins tested was impaired in ethanol-treated cells. Unlike in control cells, transcytosing proteins were observed in discrete sub-canalicular puncta en route to the canalicular surface that aligned along acetylated microtubules. We further determined that the stalled transcytosing proteins colocalized with dynein/dynactin in treated cells. No changes in vesicle association were observed for either dynein or dynactin in ethanol-treated cells, but significantly enhanced dynein binding to microtubules was observed. From these results, we propose that enhanced dynein binding to microtubules in ethanol-treated cells leads to decreased motor processivity resulting in vesicle stalling and in impaired canalicular delivery. Our studies also importantly indicate that modulating cellular acetylation levels with clinically tolerated deacetylase agonists may be a novel therapeutic strategy for treating alcoholic liver disease. PMID:25148871

Groebner, Jennifer L; Fernandez, David J; Tuma, Dean J; Tuma, Pamela L

2014-12-01

145

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

SciTech Connect

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.

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

146

Using human adipose tissue-derived mesenchymal stem cells as salvage therapy for hepatic graft-versus-host disease resembling acute hepatitis.  

PubMed

A 43-year-old woman with chronic hepatic graft-versus-host disease (GVHD) who failed previous immunosuppressive therapy with cyclosporine and prednisone was treated with tacrolimus starting on day 165 after allogeneic hematopoietic stem cell transplantation. Fifteen days later, tacrolimus was discontinued because of progressive deterioration of renal function. However, after changing treatment to human adipose tissue-derived mesenchymal stem cells (AMSC), we observed rapid and complete resolution of hepatic GVHD and renal toxicity. We concluded that it is worthwhile to administer AMSC as a treatment for common hepatic GVHD, particularly for atypical cases presenting as acute hepatitis. PMID:17580228

Fang, B; Song, Y; Zhao, R C; Han, Q; Lin, Q

2007-06-01

147

Calciphylaxis associated with acute, reversible renal failure in the setting of alcoholic cirrhosis.  

PubMed

We describe a case of calciphylaxis in a 47-year-old man with alcohol-induced end-stage liver disease and acute renal failure secondary to hepatorenal syndrome. Possible contributing factors included transiently impaired renal function, protein C and S deficiencies, elevated calcium-phosphate product, hyperphosphatemia, low serum albumin, repeated albumin infusions, and elevated alkaline phosphatase level. PMID:15097947

Chavel, Severine M; Taraszka, Karen S; Schaffer, Julie V; Lazova, Rossitza; Schechner, Jeffrey S

2004-05-01

148

Acute alcohol effects on repetition priming and word recognition memory with equivalent memory cues  

Microsoft Academic Search

Acute alcohol intoxication effects on memory were examined using a recollection-based word recognition memory task and a repetition priming task of memory for the same information without explicit reference to the study context. Memory cues were equivalent across tasks; encoding was manipulated by varying the frequency of occurrence (FOC) of words in the study lists. Twenty-two female and male social

Suchismita Ray; Marsha E. Bates

2006-01-01

149

Acute Alcohol Effects on Repetition Priming and Word Recognition Memory with Equivalent Memory Cues  

ERIC Educational Resources Information Center

Acute alcohol intoxication effects on memory were examined using a recollection-based word recognition memory task and a repetition priming task of memory for the same information without explicit reference to the study context. Memory cues were equivalent across tasks; encoding was manipulated by varying the frequency of occurrence (FOC) of words…

Ray, Suchismita; Bates, Marsha E.

2006-01-01

150

Acute Alcohol Intoxication Impairs the Hematopoietic Precursor Cell Response to Pneumococcal Pneumonia  

PubMed Central

Background Alcohol abuse is associated with an increased incidence and severity of pneumonia. In both the general population and in individuals consuming excess alcohol, Streptococcus pneumoniae is the most frequent lung infection pathogen. Alcoholic patients with pneumonia frequently present with granulocytopenia, which is predictive of increased mortality. The mechanisms underlying this impaired granulopoietic response to pneumococcal pneumonia have yet to be elucidated. Methods Acute alcohol intoxication was induced in mice 30 minutes before intrapulmonary infection with Streptococcus pneumoniae. Bone marrow and blood samples were collected. Bone marrow cells were also isolated from naïve mice and treated in vitro with plasma from mice infected with S.pneumoniae. Results Alcohol intoxication impaired the pneumococcal-induced increase in granulocyte recruitment into the alveolar space, decreased bacterial clearance from the lung, and increased mortality. Pneumococcal pneumonia significantly increased bone marrow lineage?c-Kit+Sca-1+ (LKS) cell number and colony forming unit – granulocytes and monocyte (CFU-GM) activity of these cells. Both enhanced proliferation of LKS cells and re-expression of Sca-1 surface protein on downstream progenitor cells bearing lineage?c-Kit+Sca-1? surface markers accounted for the expansion of marrow LSK cells during pneumonia. Alcohol intoxication impaired these two mechanisms of LKS cell population expansion and was associated with a relative granulocytopenia during pneumococcal lung infection. Conclusions Alcohol inhibits the hematopoietic precursor cell response to pneumonia which may serve as a mechanism underlying the granulocytopenia and impaired host defense in alcohol abusers with bacterial pneumonia. PMID:20659065

Raasch, Caroline E.; Zhang, Ping; Siggins, Robert W.; LaMotte, Lynn R.; Nelson, Steve; Bagby, Gregory J.

2013-01-01

151

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

PubMed Central

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

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

152

Chronic alcohol intake up-regulates hepatic expressions of carotenoid cleavage enzymes and peroxisomal proliferator-activated receptors in rats  

Technology Transfer Automated Retrieval System (TEKTRAN)

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 9910’-monooxygenase 2 (CMO2)...

153

Identification of gene expression profile in the rat brain resulting from acute alcohol intoxication.  

PubMed

This study aimed to identify gene expression profile in the rat brain resulting from acute alcohol intoxication (AAI). Eighteen SD rats were divided into the alcohol-treated group (n = 9) and saline control group (n = 9). Periorbital blood samples were taken to determine their blood alcohol content by gas chromatography. Tissue sections were analyzed by H and E staining and biochemical assays. Real-time reverse transcription PCR was used to validate microarray data. Statistical analysis was carried out using SPSS18.0 software (Version 18.0, SPSS Inc., Chicago, IL, USA). H and E staining demonstrated that alcohol-treated rats showed no obvious pathological changes in nerve cells compared with those in the control group. Biochemical tests revealed that alcohol-treated rats had lower superoxide dismutase activity than those in the control group (167.3 ± 10.3 U/mg vs. 189.2 ± 5.9 U/mg, P < 0.05). Furthermore, the malondialdehyde levels in alcohol-treated rats were higher than those in the control group (3.48 ± 0.24 mmol/mg vs. 2.51 ± 0.23 mmol/mg, P < 0.05). Microarray data presented 366 up-regulated genes and 300 down-regulated genes in the AAI rat brain. Gene ontology analysis identified 31 genes up-regulated and 39 down-regulated among all differentially expressed genes. Twenty-four pathways showed significant differences, including 12 pathways involved with up-regulated genes and 12 pathways involved with down-regulated genes. Selected genes showed significantly different expression in both alcohol-treated and control groups (P < 0.05). Gene expression analysis enabled clustering of alcohol intoxication-related genes by function. These genes expression may be potential targets for treatment or drug screening for acute alcohol intoxication. PMID:25218841

Kong, Ling-Yu; Li, Guang-Peng; Yang, Ping; Wu, Wei; Shi, Jin-He; Li, Xue-Liang; Wang, Wei-Zhen

2014-09-14

154

Hepatitis  

MedlinePLUS

... an important digestive liquid called bile . What Is Hepatitis? Hepatitis is an inflammation (say: in-fluh- may - ... the most common types of viral hepatitis. Continue Hepatitis A For kids, hep A is the most ...

155

Flow cytometry assay of myeloid dendritic cells (mDCs) in peripheral blood during acute hepatitis C: Possible pathogenetic mechanisms  

PubMed Central

AIM: To asses the expression of myeloid dendritic cells (CD11c+) subset during acute HCV hepatitis and its possible involvement in natural history of the infection. METHODS: We enrolled 11 patients with acute hepatitis C (AHC) (Group A), 10 patients with acute hepatitis A (AHA) (as infective control-Group B) and 10 healthy donors (group C) in this study. All patients underwent selective flow cytometry gating strategies to assess the peripheral number of the myeloid dendritic cells (mDCs) to understand the possible role and differences during acute hepatitis. RESULTS: Eight of 11 patients with acute HCV hepatitis did not show any increase of mDCs compared to healthy individuals, while a significant decrease of mDCs was found in absolute cell count (z?=?-2.37; P?acute infection, resolved the illness. CONCLUSION: The lack of increase of mDCs during acute hepatitis C might be an important factor involved in chronicization of the infection. PMID:16534853

Perrella, Alessandro; Atripaldi, Luigi; Bellopede, Pasquale; Patarino, Tommaso; Sbreglia, Costanza; Tarantino, Giovanni; Sorrentino, Paolo; Conca, Paolo; Ruggiero, Luca; Perrella, Oreste

2006-01-01

156

Acute primary toxoplasmic hepatitis in an adult cat shedding Toxoplasma gondii oocysts.  

PubMed

A 3-year-old 4-kg neutered male domestic shorthair cat died within 5 days after onset of fever and respiratory distress. At necropsy, all tissues were icteric, and the liver had a diffuse reticular pattern. Histologically, hepatitis and encephalitis were associated with Toxoplasma gondii tachyzoites. Toxoplasma gondii female gamonts and oocysts were found in epithelial cells of intact villi and in epithelial cells desquamated into the lumen. Finding of acute hepatitis and T gondii oocysts in an adult cat without detectable immunodeficiency is unusual, because adult cats rarely have clinical signs of toxoplasmosis during the oocyst-shedding phase. PMID:2276958

Dubey, J P; Zajac, A; Osofsky, S A; Tobias, L

1990-12-15

157

Acute Psychotic Symptoms due to Benzydamine Hydrochloride Abuse with Alcohol  

PubMed Central

Benzydamine hydrochloride is a locally acting nonsteroidal anti-inflammatory drug. Benzydamine hydrochloride overdose can cause stimulation of central nervous system, hallucinations, and psychosis. We presented a young man with psychotic symptoms due to benzydamine hydrochloride abuse. He received a total dose of 1000?mg benzydamine hydrochloride with alcohol for its hallucinative effects. Misuse of benzydamine hydrochloride must be considered in differential diagnosis of first-episode psychosis and physicians should consider possibility of abuse in prescribing. PMID:25343054

Acar, Yahya Ayhan; Kalkan, Mustafa; Çetin, R?dvan; Çevik, Erdem; Ç?nar, Orhan

2014-01-01

158

Acute effect of alcohol intake on sine-wave Cartesian and polar contrast sensitivity functions  

PubMed Central

The aim of this study was to assess contrast sensitivity for angular frequency stimuli as well as for sine-wave gratings in adults under the effect of acute ingestion of alcohol. We measured the contrast sensitivity function (CSF) for gratings of 0.25, 1.25, 2.5, 4, 10, and 20 cycles per degree of visual angle (cpd) as well as for angular frequency stimuli of 1, 2, 4, 24, 48, and 96 cycles/360°. Twenty adults free of ocular diseases, with normal or corrected-to-normal visual acuity, and no history of alcoholism were enrolled in two experimental groups: 1) no alcohol intake (control group) and 2) alcohol ingestion (experimental group). The average concentration of alcohol in the experimental group was set to about 0.08%. We used a paradigm involving a forced-choice method. Maximum sensitivity to contrast for sine-wave gratings in the two groups occurred at 4 cpd sine-wave gratings and at 24 and 48 cycles/360° for angular frequency stimuli. Significant changes in contrast sensitivity were observed after alcohol intake compared with the control condition at spatial frequency of 4 cpd and 1, 24, and 48 cycles/360° for angular frequency stimuli. Alcohol intake seems to affect the processing of sine-wave gratings at maximum sensitivity and at the low and high frequency ends for angular frequency stimuli, both under photopic luminance conditions. PMID:24676473

Cavalcanti-Galdino, M.K.; da Silva, J.A.; Mendes, L.C.; dos Santos, N.A.; Simas, M.L.B.

2014-01-01

159

Differences in Acute Alcohol-Induced Behavioral Responses Among Zebrafish Populations  

PubMed Central

Background With the arsenal of genetic tools available for zebrafish, this species has been successfully used to investigate the genetic aspects of human diseases from developmental disorders to cancer. Interest in the behavior and brain function of zebrafish is also increasing as CNS disorders may be modeled and studied with this species. Alcoholism and alcohol abuse are among the most devastating and costliest diseases. However, the mechanisms of these diseases are not fully understood. Zebrafish has been proposed as a model organism to study such mechanisms. Characterization of alcohol’s effects on zebrafish is a necessary step in this research. Methods Here, we compare the effects of acute alcohol (EtOH) administration on the behavior of zebrafish from 4 distinct laboratory-bred populations using automated as well as observation based behavioral quantification methods. Results Alcohol treatment resulted in significant dose-dependent behavioral changes but the dose–response trajectories differed among zebrafish populations. Conclusions The results demonstrate for the first time a genetic component in alcohol responses in adult zebrafish and also show the feasibility of high throughput behavioral screening. We discuss the exploration and exploitation of the genetic differences found. PMID:18652595

Gerlai, Robert; Ahmad, Fahad; Prajapati, Sonal

2009-01-01

160

Acute Inflammatory Bowel Disease Complicating Chronic Alcoholism and Mimicking Carcinoid Syndrome  

PubMed Central

We report the case of a woman with a history of chronic alcohol abuse who was hospitalized with diarrhea, severe hypokalemia refractory to potassium infusion, nausea, vomiting, abdominal pain, alternations of high blood pressure with phases of hypotension, irritability and increased urinary 5-hydroxyindoleacetic acid and cortisol. Although carcinoid syndrome was hypothesized, abdominal computed tomography and colonoscopy showed non-specific inflammatory bowel disease with severe colic wall thickening, and multiple colic biopsies confirmed non-specific inflammation with no evidence of carcinoid cells. During the following days diarrhea slowly decreased and the patient's condition progressively improved. One year after stopping alcohol consumption, the patient was asymptomatic and serum potassium was normal. Chronic alcohol exposure is known to have several deleterious effects on the intestinal mucosa and can favor and sustain local inflammation. Chronic alcohol intake may also be associated with high blood pressure, behavior disorders, abnormalities in blood pressure regulation with episodes of hypotension during hospitalization due to impaired baroreflex sensitivity in the context of an alcohol withdrawal syndrome, increased urinary 5-hydroxyindoleacetic acid as a result of malabsorption syndrome, and increased urinary cortisol as a result of hypothalamic-pituitary-adrenal axis dysregulation. These considerations, together with the regression of symptoms and normalization of potassium levels after stopping alcohol consumption, suggest the intriguing possibility of a alcohol-related acute inflammatory bowel disease mimicking carcinoid syndrome. PMID:22949895

Ballo, Piercarlo; Dattolo, Pietro; Mangialavori, Giuseppe; Ferro, Giuseppe; Fusco, Francesca; Consalvo, Matteo; Chiodi, Leandro; Pizzarelli, Francesco; Zuppiroli, Alfredo

2012-01-01

161

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

Microsoft Academic Search

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

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

2000-01-01

162

Low dose acute alcohol effects on GABA A receptor subtypes  

Microsoft Academic Search

GABAA receptors (GABAARs) are the main inhibitory neurotransmitter receptors and have long been implicated in mediating at least part of the acute actions of ethanol. For example, ethanol and GABAergic drugs including barbiturates and benzodiazepines share many pharmacological properties. Besides the prototypical synaptic GABAAR subtypes, nonsynaptic GABAARs have recently emerged as important regulators of neuronal excitability. While high doses (?100 mM)

Martin Wallner; H. Jacob Hanchar; Richard W. Olsen

2006-01-01

163

Hospitalisation for an alcohol-related cause among injecting drug users in Scotland: Increased risk following diagnosis with hepatitis C infection  

Microsoft Academic Search

BackgroundThe rate of hepatitis C (HCV) related liver disease progression is known to be strongly associated with alcohol consumption, yet there are very few data on alcohol use in injecting drug users (IDUs), who represent 90% of Scotland's HCV-diagnosed population. To investigate the extent of alcohol use in IDUs, we used hospitalisation with an alcohol-related diagnosis as an indicator for

Scott A. McDonald; Sharon J. Hutchinson; Sheila M. Bird; Chris Robertson; Peter R. Mills; John F. Dillon; David J. Goldberg

2011-01-01

164

Acute and chronic effects of dinner with alcoholic beverages on nitric oxide metabolites in healthy men.  

PubMed

1. The present study investigated the acute and chronic effect of dinner with alcoholic beverages on serum nitric oxide (NO) metabolites, namely nitrate and nitrite (NOx), in 11 healthy, non-smoking middle-aged men. 2. In a randomized, diet-controlled, cross-over trial, subjects consumed dinner with four glasses of red wine, beer, spirits (Dutch gin) or sparkling mineral water (control) for 3 weeks. At the end of each 3 week period, serum NOx concentrations were measured just before and 1, 5 and 13 h after dinner. 3. Serum NOx concentrations were approximately 50% higher 1 and 5 h after dinner with any beverage compared with just before dinner (P = 0.0001). At 1 h after dinner, the serum NOx concentration was approximately 11% lower after dinner with alcoholic beverages compared with concentrations observed after dinner with water (P = 0.01). The fasted serum NOx concentration (13 h after dinner) was similar to the preprandial concentration and there were no differences in serum NOx concentrations between the alcoholic beverages. 4. Food intake acutely and transiently increased serum NOx concentrations, an effect that was slightly attenuated if combined with alcoholic beverages. Chronic moderate alcohol consumption had no effect on serum NOx concentration. PMID:12823267

Sierksma, Aafje; van der Gaag, Martijn S; Grobbee, Diederick E; Hendriks, Henk F J

2003-07-01

165

High precision liquid chromatography analysis of dopaminergic and serotoninergic responses to acute alcohol exposure in zebrafish  

PubMed Central

Zebrafish is gaining popularity in behavioral neuroscience in general and in alcohol research in particular. Alcohol is known to affect numerous molecular mechanisms depending on dose and administration regimen. Prominent among these mechanisms are several neurotransmitter systems. Here we analyze the responses of the dopaminergic and serotoninergic neurotransmitter systems of zebrafish to acute alcohol treatment (1 h long exposure of adult fish to 0.00%, 0.25%, 0.50%, or 1.00% ethyl alcohol) by testing the concentration of dopamine, its metabolite DOPAC, and serotonin and its metabolite 5-HIAA from whole brain extracts. We utilize a sensitive HPLC method and describe significant alcohol induced changes in zebrafish for the first time. We show that dopamine significantly increased in a quasi-linear dose dependent manner, DOPAC showed a smaller apparent increase which was non-significant, while both serotonin and 5-HIAA showed a significant increase only in the highest acute dose group. We discuss the methodological novelty of our work and theorize about the implications of the neurotransmitter level changes from a behavioral perspective. PMID:19378384

Chatterjee, Diptendu; Gerlai, Robert

2009-01-01

166

Acute hepatitis A in Italy: incidence, risk factors and preventive measures.  

PubMed

The incidence of, and risk factors for, acute hepatitis A (AHA) were assessed by using data collected from the Italian surveillance system of acute viral hepatitis (SEIEVA). To this end, a case-control study within a population-based surveillance for acute viral hepatitis was performed. AHA incidence has been estimated since 1991; the association with considered risk factors was analysed from 2001 to 2006 employing cases of acute hepatitis B (AHB) as controls. The incidence of AHA declined from 4 / 100 000 in 1991 to 1.4/100 000 in 2006, with a peak during 1996-1998 due to an outbreak in southern Italy. The incidence of AHA was highest among persons aged 15-24 years. The case-fatality rate was 2.9 / 10 000. Contact with individuals with AHA [adjusted OR (OR(adj)) = 3.8, 95% CI 2.7-5.5; population-attributable risk (PAR) = 7.5%], travelling to endemic areas (OR(adj) = 3.1, 95% CI = 2.6-3.8; PAR = 19.5%), ingestion of raw shellfish (OR(adj) = 1.8, 95% CI = 1.6-2.1; PAR = 26.6%), and cohabitation with day care children (OR(adj) = 1.3, 95% CI = 1.01-1.7; PAR = 2.3%) were the main important risk factors. In 2003, an outbreak, with high case-fatality rate occurred among intravenous drug users, in a central Italian town. A weak association was found for male homosexuality when acute hepatitis C cases were employed as controls (OR(adj) = 1.4 CI, 95% CI = 1.1-1.9). Hepatitis A virus infections are currently occurring more frequently in adults, in whom the disease is most severe. In conclusion, looking at the attributable risks, at present most of the AHA infections are due to shellfish consumption, travel to endemic areas and contact with patients with AHA. Vaccination of individuals at increased risk of infection, as well as persons with underling liver disease and those at increased risk of complications, combined with surveillance of shellfish retail outlets are efficient control measures. PMID:18837830

Tosti, M E; Spada, E; Romanò, L; Zanetti, A; Mele, A

2008-10-01

167

Behavioral economic analysis of stress effects on acute motivation for alcohol.  

PubMed

Due to issues of definition and measurement, the heavy emphasis on subjective craving in the measurement of acute motivation for alcohol and other drugs remains controversial. Behavioral economic approaches have increasingly been applied to better understand acute drug motivation, particularly using demand curve modeling via purchase tasks to characterize the perceived reinforcing value of the drug. This approach has focused on using putatively more objective indices of motivation, such as units of consumption, monetary expenditure, and price sensitivity. To extend this line of research, the current study used an alcohol purchase task to determine if, compared to a neutral induction, a personalized stress induction would increase alcohol demand in a sample of heavy drinkers. The stress induction significantly increased multiple measures of the reinforcing value of alcohol to the individual, including consumption at zero price (intensity), the maximum total amount of money spent on alcohol (Omax ), the first price where consumption was reduced to zero (breakpoint), and the general responsiveness of consumption to increases in price (elasticity). These measures correlated only modestly with craving and mood. Self-reported income was largely unrelated to demand but moderated the influence of stress on Omax . Moderation based on CRH-BP genotype (rs10055255) was present for Omax , with T allele homozygotes exhibiting more pronounced increases in response to stress. These results provide further support for a behavioral economic approach to measuring acute drug motivation. The findings also highlight the potential relevance of income and genetic factors in understanding state effects on the perceived reinforcing value of alcohol. PMID:25413719

Owens, Max M; Ray, Lara A; MacKillop, James

2014-11-20

168

Exercise capacity is not impaired after acute alcohol ingestion: a pilot study.  

PubMed

The usage of alcohol is widespread, but the effects of acute alcohol ingestion on exercise performance and the stress hormone axis are not fully elucidated.We studied 10 healthy white men, nonhabitual drinkers, by Doppler echocardiography at rest, spirometry, and maximal cardiopulmonary exercise test (CPET) in two visits (2-4 days in between), one after administration of 1.5?g/kg ethanol (whisky) diluted at 15% in water, and the other after administration of an equivalent volume of water. Plasma levels of NT-pro-BNP, cortisol, and adrenocorticotropic hormone (ACTH) were also measured 10?min before the test, at maximal effort and at the third minute of recovery. Ethanol concentration was measured from resting blood samples by gas chromatography and it increased from 0.00?±?0.00 to 1.25?±?0.54‰ (P?acute alcohol intake, whereas ACTH, cortisol, and NT-pro-BNP nonsignificantly increased in all phases of the test. CPET data suggested a trend toward a slight reduction of exercise performance (peak VO2?=?3008?±?638 vs. 2900?±?543?ml/min, ns; peak workload?=?269?±?53 vs. 249?±?40?W, ns; test duration 13.7?±?2.2 vs. 13.3?±?1.7?min, ns; VE/VCO2 22.1?±?1.4 vs. 23.3?±?2.9, ns). Ventilatory equivalent for carbon dioxide at rest was higher after alcohol intake (28?±?2.5 vs. 30.4?±?3.2, P?=?0.039) and maximal respiratory exchange ratio was lower after alcohol intake (1.17?±?0.02 vs. 1.14?±?0.04, P?=?0.04). In conclusion, we showed that acute alcohol intake in healthy white men is associated with a nonsignificant exercise performance reduction and stress hormone stimulation, with an unchanged exercise metabolism. PMID:25083719

Popovic, Dejana; Damjanovic, Svetozar S; Plecas-Solarovic, Bosiljka; Peši?, Vesna; Stojiljkovic, Stanimir; Banovic, Marko; Ristic, Arsen; Mantegazza, Valentina; Agostoni, Piergiuseppe

2014-08-01

169

Acute Thrombocytopenia: An Unusual Complication Occurring After Drug-Eluting Microspheres Transcatheter Hepatic Chemoembolization  

SciTech Connect

Image-guided transcatheter hepatic chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma and liver metastases from neuroendocrine tumors, colorectal carcinomas, and uveal melanomas. Although the technique is relatively safe, it has been associated with several complications. We report the cases of two patients with colorectal liver metastases who developed acute thrombocytopenia a few hours after TACE. To our knowledge, acute thrombocytopenia occurring after TACE with drug-eluting microspheres has not yet been reported. Here we discuss the hypothetical etiopathogenetic mechanisms.

Poggi, Guido, E-mail: guido.poggi@fsm.it [Istituto Scientifico di Pavia, Department of Oncology, IRCCS Fondazione S. Maugeri (Italy); Quaretti, Pietro, E-mail: pquaretti@smatteo.pv.it [IRCCS Policlinico San Matteo, Department of Interventional Radiology (Italy); Montagna, Benedetta, E-mail: b.montagna@fsm.it; Sottotetti, Federico, E-mail: f.sottotetti@fsm.it; Tagliaferri, Barbara, E-mail: b.tagliaferri@fsm.it; Pozzi, Emma, E-mail: v.pozzi@fsm.it; Amatu, Alessio, E-mail: a.amatu@fsm.it; Pagella, Chiara; Bernardo, Giovanni, E-mail: g.bernardo@fsm.it [Istituto Scientifico di Pavia, Department of Oncology, IRCCS Fondazione S. Maugeri (Italy)

2011-02-15

170

Recognition and treatment of acute alcohol withdrawal syndromes.  

PubMed

The alcohol withdrawal syndromes are generally self-limited processes from which spontaneous recovery can be anticipated. To achieve this outcome, the various types of withdrawal must be managed in such a way as to prevent the occurrence of life-threatening situations. This begins with a good initial evaluation, followed by the appropriate pharmacologic and behavioral steps to control the severity of withdrawal symptoms and to manage complications. Once the withdrawal process is completed, the patient can then be entered into a long-term treatment program. PMID:6335250

Holloway, H C; Hales, R E; Watanabe, H K

1984-12-01

171

An acute psychosocial stressor increases drinking in non-treatment-seeking alcoholics  

Microsoft Academic Search

Rationale  Although studies suggest that stress is an important reason for relapse in alcoholics, few controlled studies have been conducted\\u000a to examine this assumption. Evidence of stress-potentiated drinking would substantiate this clinical observation and would\\u000a contribute to the development of a model that would be valuable to alcohol treatment research.\\u000a \\u000a \\u000a \\u000a \\u000a Objectives  The hypothesis was tested that an acute psychosocial stressor, the Trier

Suzanne E. Thomas; Amy K. Bacon; Patrick K. Randall; Kathleen T. Brady; Ronald E. See

172

Acute kidney injury after hepatic ischemia and reperfusion injury in mice  

PubMed Central

Hepatic ischemia reperfusion (IR) is the leading cause of acute liver failure (ALF) during the perioperative period and patients with ALF frequently develop acute kidney injury (AKI). There is no effective therapy for AKI associated with ALF because pathomechanisms are incompletely characterized, in part due to the lack of an animal model. In this study, we characterize a novel murine model of AKI following hepatic IR. Mice subjected to ~70% liver IR not only developed acute liver dysfunction, but also developed severe AKI 24 hr after liver injury. Mice subjected to liver IR developed histological changes of acute tubular injury including focal proximal tubular cell necrosis involving the S3 segment, cortical tubular ectasia, focal tubular simplification and granular bile/heme cast formation. In addition, there was focal interstitial edema and hyperplasia of the juxtaglomerular apparatus. Inflammatory changes in the kidney after hepatic IR included neutrophil infiltration of the interstitium and upregulation of several pro-inflammatory mRNAs (tumor necrosis factor-?, keratinocyte derived cytokine, monocyte chemotactic protein-1, macrophage inflammatory protein-2, intercellular adhesion molecule-1). In addition, marked renal endothelial cell apoptosis was detected involving peritubular interstitial capillaries, accompanied by increased renal vascular permeability. Finally, there was severe disruption of renal proximal tubule epithelial filamentous-actin. Our results show that AKI rapidly and reproducibly develops in mice after hepatic IR and is characterized by renal tubular necrosis, inflammatory changes and interstitial capillary endothelial apoptosis. Our murine model of AKI after liver injury closely mimics human AKI associated with ALF and may be useful in delineating the mechanisms and potential therapies for this common clinical condition. PMID:19079326

Lee, H. Thomas; Park, Sang Won; Kim, Mihwa; D’Agati, Vivette D.

2008-01-01

173

Trihalomethane Comparative Toxicity: Acute Renal and Hepatic Toxicity of Chloroform and Bromodichloromethane Following Aqueous Gavage  

Microsoft Academic Search

Bromodichloromethane (BDCM) and chloroform (CHCl3) are by-products of drinking water chlorination and are the two most prevalent trihalomethanes (THMs) in finished drinking water. To date, no comprehensive comparison of the acute renal and hepatic effects of BDCM and CHCl3following oral gavage in an aqueous dosing vehicle has been conducted. To characterize BDCM- and CHCl3-induced nephro- and hepatotoxicity following aqueous gavage

Patrick D. Lilly; Tracey M. Ross; Rex A. Pegramt

1997-01-01

174

Acute cholestatic hepatitis caused by amoxicillin/clavulanate  

PubMed Central

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

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

2013-01-01

175

Detection and characterization of circulating immune complexes during acute exacerbation of chronic viral hepatitis.  

PubMed

For the detection and characterization of circulating immune complexes (CIC) in various liver diseases, a Clq binding test was used. Though the CIC level was almost normal in HB surface antigen (HBsAg) positive asymptomatic carriers, the level increased in patients with liver diseases. During acute exacerbation of chronic viral hepatitis, the CIC level reached peaks 1 to 3 weeks before and after the hepatic cell necrosis. Study of the sedimentation rates of CIC in various liver diseases showed CIC in the 19s-22s region and in the 7s-19s region. In acid buffer, CIC was dissociated into 5 to 6 components by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). In one case of HBsAg positive severe chronic aggressive hepatitis, CIC was composed of HBsAg, IgG and another three or four undetermined components. During acute exacerbation of chronic hepatitis, minor changes of these dissociation patterns of CIC were observed. PMID:6450515

Araki, K; Tsuji, T; Onoue, K; Tsuchiya, M; Shinohara, T; Inoue, J; Nagashima, H

1980-03-01

176

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

PubMed Central

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

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

2013-01-01

177

Acute effects of mildly intoxicating levels of alcohol on left ventricular function in conscious dogs.  

PubMed Central

We assessed the effect of alcohol, before and after autonomic blockade, on left ventricular (LV) performance in conscious dogs. 10 animals were instrumented to determine LV volume from ultrasonic LV internal dimensions and measure LV pressure with a micromanometer. The animals were studied in the conscious state after full recovery from the operation. Blood alcohol was undetectable before and 67 +/- 14 mg/dl (mean +/- SD) at 20 min after alcohol administration. In response to alcohol, the LV systolic pressure was reduced slightly, the left ventricular end-diastolic pressure increased slightly. The maximum time derivative of LV pressure (dP/dtmax) and stroke volume were decreased. The end-systolic volume (VES), as well as effective arterial elastance, were significantly increased. There was no significant change in heart rate. Variably loaded pressure-volume loops were generated by acute caval occlusion before, immediately, and 20 min after the intravenous infusion of alcohol (0.2 g/kg). Three measures of LV performance were derived from these variably loaded pressure-volume loops: the end-systolic pressure-volume relation; the stroke work-end-diastolic volume relation; and maximum dP/dt-VED relation. The slopes of all three relations were significantly decreased in response to alcohol, and all three relations were shifted toward the right, indicating a depression of LV contractile performance. Similar, but greater depressions of LV performance with alcohol were observed following autonomic blockade. LV performance was restored by infusing dobutamine. We conclude that mildly intoxicating levels of alcohol (blood concentration less than 100 mg/dl) are capable of producing LV contractile depression in conscious animals, which is more marked after autonomic blockade. This suggests that patients with impaired LV function should avoid even small amounts of alcohol. PMID:2347916

Cheng, C P; Shihabi, Z; Little, W C

1990-01-01

178

Brain modifications after acute alcohol consumption analyzed by resting state fMRI.  

PubMed

Resting-state functional magnetic resonance imaging (fMRI) is a recent breakthrough in neuroimaging research able to describe "in vivo" the spontaneous baseline neuronal activity characterized by blood oxygen level dependent (BOLD) signal fluctuations at slow frequency (0.01-0.1Hz) that, in the absence of any task, forms spatially distributed functional connectivity networks, called resting state networks (RSNs). The aim of this study was to investigate, in the young and healthy population, the changing of the RSNs after acute ingestion of an alcohol dose able to determine a blood concentration (0.5g/L) that barely exceeds the legal limits for driving in the majority of European Countries. Fifteen healthy volunteers underwent two fMRI sessions using a 1.5T MR scanner before and after alcohol oral consumption. The main sequence acquired was EPI 2D BOLD, one per each session. To prevent the excessive alcohol consumption the subjects underwent the estimation of blood rate by breath test and after the stabilization of blood alcohol level (BAL) at 0.5g/L the subjects underwent the second fMRI session. Functional data elaboration was carried out using the probabilistic independent component analysis (PICA). Spatial maps so obtained were further organized, with MELODIC multisession temporal concatenation FSL option, in a cluster representing the group of pre-alcohol sessions and the group of post-alcohol sessions, followed by the dual regression approach in order to evaluate the increase or decrease in terms of connectivity in the RSNs between the two sessions at group level. The results we obtained reveal that acute consumption of alcohol reduces in a significant way the BOLD signal fluctuations in the resting brain selectively in the sub-callosal cortex (SCC), in left temporal fusiform cortex (TFC) and left inferior temporal gyrus (ITG), which are cognitive regions known to be part of the reward brain network and the ventral visual system. PMID:23680187

Spagnolli, Federica; Cerini, Roberto; Cardobi, Nicolò; Barillari, Marco; Manganotti, Paolo; Storti, Silvia; Mucelli, Roberto Pozzi

2013-10-01

179

Pretranslational modulation of acute phase hepatic protein synthesis by murine recombinant interleukin 1 (IL1) and purified human IL1  

Microsoft Academic Search

The acute phase response is a systemic reaction to inflammation or tissue injury. It is characterized by complex changes that include fever, leukocytosis, increased muscle proteolysis, altered carbohydrate and trace metal metabolism, and a pronounced change in hepatic protein synthesis (1). Within several hours of an acute phase stimulus, the plasma concentrations of C-reactive protein and serum amyloid A (SAA)

G. Ramadori; J. D. SIPE; C. A. DINARELLO; S. B. MIZEL; H. R. COLTEN

1985-01-01

180

Acute Alcohol Modulates Cardiac Function as PI3K/Akt Regulates Oxidative Stress  

PubMed Central

Background Clinical manifestations of alcohol abuse on the cardiac muscle include defective contractility with the development of heart failure. Interestingly, low alcohol consumption has been associated with reduced risk of cardiovascular disease. Although several hypotheses have been postulated for alcoholic cardiomyopathy and for the low-dose beneficial cardiovascular effects, the precise mechanisms and mediators remain largely undefined. We hypothesize that modulation of oxidative stress by PI3K/Akt plays a key role in the cardiac functional outcome to acute alcohol exposure. Methods Thus, acutely exposed rat cardiac tissue and cardiocytes to low (LA: 5 mM), moderate (MA: 25 mM), and high (HA: 100 mM) alcohol were assessed for markers of oxidative stress in the presence and absence of PI3K/Akt activators (IGF-1 0.1 ?M or constitutively active PI3K: Ad.BD110 transfection) or inhibitor (LY294002 1 ?Mor Akt-negative construct Ad.Akt(K179M) transfection). Results Acute LA reduced Akt, superoxide dismutase (SOD-3) and NF?B, ERK1, and p38 MAPK gene expression. Acute HA only increased that of SOD-3 and NF?B. These effects were generally inhibited by Ad.Akt(K179M) and enhanced with Ad.BD110 transfection. In parallel, LA reduced but HA enhanced Akt activity, which was reversed by IGF-1 and inhibited by Ad.Akt(K179M), respectively. Also, LA reduced caspase 3/7 activity and oxidative stress, while HA increased both. The former was blocked, while the latter effect was enhanced by Ad.Akt(K179M). The reverse was true with PI3K/Akt activation. This translated into reduced viability with HA, with no effect with LA. On the functional level, acute LA improved cardiac output and ejection fraction, mainly through increased stroke volume. This was accompanied with enhanced end-systolic pressure–volume relationship and preload recruitable stroke work. Opposite effect was recorded for HA. LA and HA in vivo functional effects were alleviated by LY and enhanced by IGF-1 treatment. Conclusions Acute LA and HA seem to oppositely affect cardiac function through modulation of oxidative stress where PI3K/Akt plays a pivotal role. PMID:24962888

Umoh, Nsini A.; Walker, Robin K.; Al-Rubaiee, Mustafa; Jeffress, Miara A.; Haddad, Georges E.

2015-01-01

181

Hepatic and Fecal Metabolomic Analysis of the Effects of Lactobacillus rhamnosus GG on Alcoholic Fatty Liver Disease in Mice.  

PubMed

The interactions among the gut, liver, and immune system play an important role in liver disease. Probiotics have been used for the treatment and prevention of many pathological conditions, including liver diseases. Comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOF MS) was used herein, in conjunction with chemometric data analysis, to identify metabolites significantly affected by probiotics in mice fed with or without alcohol. The metabolomics analysis indicates that the levels of fatty acids increased in mouse liver and decreased in mouse feces when mice were chronically exposed to alcohol. Supplementing the alcohol-fed mice with culture supernatant from Lactobacillus rhamnosus GG (LGGs) normalized these alcohol-induced abnormalities and prevented alcoholic liver disease (ALD). These results agree well with previous studies. In addition to diet-derived long chain fatty acids (LCFAs), LGGs may positively modify the gut's bacterial population to stimulate LCFA synthesis, which has been shown to enhance intestinal barrier function, reduce endotoxemia, and prevent ALD. We also found that several amino acids, including l-isoleucine, a branched chain amino acid, were downregulated in the liver and fecal samples from animals exposed to alcohol and that the levels of these amino acids were corrected by LGGs. These results demonstrate that LGGs alleviates alcohol-induced fatty liver by mechanisms involving increasing intestinal and decreasing hepatic fatty acids and increasing amino acid concentration. PMID:25592873

Shi, Xue; Wei, Xiaoli; Yin, Xinmin; Wang, Yuhua; Zhang, Min; Zhao, Cuiqing; Zhao, Haiyang; McClain, Craig J; Feng, Wenke; Zhang, Xiang

2015-02-01

182

Concurrent acute interstitial pneumonia and pulmonary embolism during treatment with peginterferon alpha-2a and ribavirin in a patient with hepatitis C  

PubMed Central

The case presented is the first patient with concurrent acute interstitial pneumonia and pulmonary embolism associated with combined treatment of peginterferon and ribavirin for hepatitis C. PMID:25097288

Çoban, Hikmet; Yahyaoglu, Mehmet; Vatan, M. Bülent

2014-01-01

183

Epidemiology of acute and chronic hepatitis B and delta over the last 5 decades in Italy  

PubMed Central

The spread of hepatitis B virus (HBV) infection has gradually decreased in Italy in the last 5 decades as shown by the steady reduction in the incidence rates of acute hepatitis B, from 10/100000 inhabitants in 1984 to 0.85/100000 in 2012, and by the reduced prevalence of hepatitis B surface antigen (HBsAg)-positive cases among chronic hepatitis patients with different etiologies, from 60% in 1975 to about 10% in 2001. The prevalence of HBsAg chronic carriers in the general population also decreased from nearly 3% in the 1980s to 1% in 2010. Linked to HBV by its characteristics of defective virus, the hepatitis delta virus (HDV) has shown a similar epidemiological impact on the Italian population over time. The incidence of acute HDV infection decreased from 3.2/100000 inhabitants in 1987 to 0.8/100000 in 2010 and the prevalence of HDV infection in HBsAg chronic carriers decreased from 24% in 1990 to 8.5% in 2006. Before the beneficial effects of HBV mass vaccination introduced in 1991, the decreased endemicity of HBV and HDV infection in Italy paralleled the improvement in screening blood donations, the higher standard of living and impressive reduction in the birth rate associated with a marked reduction in the family size. A further contribution to the decline in HBV and HDV infections most probably came from the media campaigns to prevent the spread of human immunodeficiency virus infection by focusing the attention of the general population on the same routes of transmission of viral infections such as unsafe sexual intercourse and parenteral exposures of different kinds. PMID:24976701

Sagnelli, Evangelista; Sagnelli, Caterina; Pisaturo, Mariantonietta; Macera, Margherita; Coppola, Nicola

2014-01-01

184

Linagliptin alleviates hepatic steatosis and inflammation in a mouse model of non-alcoholic steatohepatitis.  

PubMed

Non-alcoholic steatohepatitis (NASH) is a primary cause of cirrhosis and hepatocellular carcinoma. Dipeptidyl peptidase (DPP)-4 inhibitors are established therapies for type 2 diabetes and although DPP-4 inhibitors can reduce hepatic steatosis, their impact on local inflammation and fibrosis in NASH remains unknown. Using two different experimental treatment regimens (4- and 2-week treatments) in streptozotocin-treated neonatal mice on a high-fat diet, we show that the DPP-4 inhibitor linagliptin (10 and 30 mg/kg) significantly attenuated the NAS score from 4.9 ± 0.6 to 3.7 ± 0.4 and 3.6 ± 0.3, respectively, in the 4-week study. In the 2-week study, linagliptin 10 mg/kg significantly reduced NAS score from 4.1 ± 0.4 to 2.4 ± 0.4. Telmisartan was used as a positive control in both studies and lowered NAS score to 1.9 ± 0.7 and 1.4 ± 0.3, respectively. Due to streptozotocin treatment, elevated glucose levels were unchanged by either drug treatment. Further, linagliptin 10 mg/kg significantly reduced mRNA levels of SOCS-3 (from 1.68 ± 0.2 to 0.83 ± 0.08), IFN-? (from 4.0 ± 0.5 to 2.3 ± 0.3), and TNF-? (from 5.7 ± 0.5 to 2.13 ± 0.3). The latter observation was confirmed by immunohistochemistry of TNF-? in liver specimens. In addition, using microautoradiography, we showed that the distribution of radiolabeled linagliptin was heterogeneous with the highest density associated with interlobular bile ducts and portal tracts (acini). In conclusion, these studies confirm that linagliptin has high exposure in hepatic tissue and has both anti-inflammatory and anti-steatotic activity in NASH. PMID:24048504

Klein, Thomas; Fujii, Masato; Sandel, Jan; Shibazaki, Yuichiro; Wakamatsu, Kyoko; Mark, Michael; Yoneyama, Hiroyuki

2014-09-01

185

A Herbal Composition of Semen Hoveniae, Radix Puerariae, and Fructus Schisandrae Shows Potent Protective Effects on Acute Alcoholic Intoxication in Rodent Models  

PubMed Central

This study is designed to evaluate the effects of a herbal composition of Semen Hoveniae, Radix Puerariae and Fructus Schisandrae (SRF) against acute alcoholic intoxication. The animals were treated with SRF extract (SRFE) for 14 days, and ethanol was conducted subsequent to the final treatment. The effects of SRFE on righting reflex, inebriety rates, kinetic parameters of blood ethanol and acetaldehyde were determined. In addition; levels of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), the activities of cytochrome P450 2E1 (CYP2E1), selected antioxidative enzymes, and the contents of malonaldehyde (MDA) were measured. SRFE-pretreated rodents exhibited lower rates of intoxication, longer times to loss of righting reflex, and shortened times to recovery of righting reflex than in controls. The peak concentrations and area under the time-concentration curves were lower in the pretreated animals than in controls, which corresponded to higher levels of ADH and ALDH in both gastrointestines and livers of the SRFE-treated animals. The activities of CYP2E1 were lower in SRFE-pretreated animals, which also exhibited higher activities of some antioxidant enzymes and lower hepatic MDA levels. These findings suggest that the anti-inebriation effects of SRFE may involve inhibition of ethanol absorption, promotion of ethanol metabolism, and enhancing hepatic anti-oxidative functions. PMID:23118795

Xiong, Jie; Guo, Yu; Li, Lu-yi; Hu, Hang; Qu, Xin-lan; Sun, Xi-zhen; Liu, Sheng-hua; Wang, Hui

2012-01-01

186

Increased loss and decreased synthesis of hepatic glutathione after acute ethanol administration. Turnover studies.  

PubMed Central

The effect of acute ethanol administration on rates of synthesis and utilization of hepatic glutathione (GSH) was studied in rats after a pulse of [35S]cysteine. A 35% decrease in hepatic GSH content 5h after administration of 4 g of ethanol/kg body wt. was accompanied by a 33% increase in the rate of GSH utilization. The decrease occurred without increases in hepatic oxidized glutathione (GSSG) or in the GSH/GSSG ratio. The rate of non-enzymic condensation of GSH with acetaldehyde could account for only 6% of the rate of hepatic GSH disappearance. The increased loss of [35S]GSH induced by ethanol was not accompanied by an increased turnover; rather, a 30% inhibition of GSH synthesis balanced the increased rate of loss, leaving the turnover rate unchanged. The rate of acetaldehyde condensation with cysteine in vitro occurred at about one-third of the rate of GSH loss in ethanol-treated animals. However, ethanol induced only a minor decrease in liver cysteine content, which did not precede, but followed, the decrease in GSH. The characteristics of 2-methylthiazolidine-4-carboxylic acid, the condensation product between acetaldehyde and cysteine, were studied and methodologies were developed to determine its presence in tissues. It was not found in the liver of ethanol-treated animals. Ethanol administration led to a marked increase (47%) in plasma GSH in the post-hepatic inferior vena cava, but not in its pre-hepatic segment. Data suggest that an increased loss of GSH from the liver constitutes an important mechanism for the decrease in GSH induced by ethanol. In addition, an inhibition of GSH synthesis is observed. PMID:3977847

Speisky, H; MacDonald, A; Giles, G; Orrego, H; Israel, Y

1985-01-01

187

[Acute hepatitis due to infectious mononucleosis in a 21-year-old-man].  

PubMed

A 21-year-old mole was admitted because of fever, fatigue, headache, pharyngitis, abdominal pain, loss of appetite, vomiting and dark urine for three days. The patient denied recent use of medicines or any other drug. His physical examination disclosed jaundice, hepato-splenomegaly, whitish-yellow covered tonsils, bilateral anterior and posterior cervical lymph node enlargement associated with edema on the face and neck. Routine blood tests detected abnormalities in serum bilirubins and liver enzymes (total bilirubin: 14.5 mg/dl, direct-reacting bilirubin: 12.9 mg/dl, AST: 697 U/l, ALT: 619 U/l, alkaline phosphatases: 260 U/l, and GGT: 413 U/l). Serological tests showed negative results for viral hepatitis, cytomegalovirus, HIV-1 and HIV-2, and toxoplasmosis markers, while serology for recent infection by EBV was positive (IgM: 70 and 29 U/ml; EBV IgG: 25 and 156 U/ml). Although infrequently, EBV infection can cause acute hepatitis with accentuated cholestatic jaundice (5% of cases), which may constitute an additional diagnostic challenge for primary care physicians. The patient improved with supportive management and was discharged after 12 days. This case study might contribute to increase the suspicion index about acute hepatitis related to EBV. PMID:24356741

Modesto Dos Santos, Vitorino; Da Costa Arruda, Zilcem; De Farias Polcheira, Maira; Da Silva De Souza, Diogo Wagner; Rodrigues Oliveira Santos, Alessandra Maria; Santos Corrêa Da Costa, Marcela

2013-07-01

188

Clinical course and management of acute and chronic viral hepatitis during pregnancy.  

PubMed

Pregnancy is a para-physiologic condition, which usually evolves without any complications in the majority of women, even if in some circumstances moderate or severe clinical problems can also occur. Among complications occurring during the second and the third trimester very important are those considered as concurrent to pregnancy such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, HELLP syndrome and acute fatty liver of pregnancy. The liver diseases concurrent to pregnancy typically occur at specific times during the gestation and they may lead to significant maternal and foetal morbidity and mortality. Commonly, delivery of the foetus, even preterm, usually terminates the progression of these disorders. All chronic liver diseases, such as chronic viral hepatitis, autoimmune hepatitis, Wilson's disease, and cirrhosis of different aetiologies may cause liver damage, independently from pregnancy. In this review we will also comment the clinical implications of pregnancies occurring in women who received a orthotopic liver transplantation (OLT) Therefore, the management of immunosuppressive therapy before and after the delivery in women who received liver transplant is becoming a relevant clinical issue. Finally, we will focus on acute and chronic viral hepatitis occurring during pregnancy, on management of advanced liver disease and we will review the literature on the challenging issue regarding pregnancy and OLT. PMID:25288051

Licata, A; Ingrassia, D; Serruto, A; Soresi, M; Giannitrapani, L; Montalto, G; Craxì, A; Almasio, P L

2014-10-01

189

The inflammasome in alcoholic hepatitis: Its relationship with Mallory-Denk body formation.  

PubMed

Recent studies indicate that the inflammasome activation plays important roles in the pathogenesis of alcoholic hepatitis (AH). Nod-like receptor protein 3 (NLRP3) is a key component of the macromolecular complex that is so called the inflammasome that triggers caspase 1-dependent maturation of the precursors of IL-1? and IL-18 cytokines. It is also known that the adaptor proteins including apoptosis-associated speck-like protein containing CARD (ASC) and the mitochondrial antiviral signaling protein (MAVS) are necessary for NLRP3-dependent inflammasome function. Steatohepatitis frequently includes Mallory-Denk body (MDB) formation. In the case of alcoholic steatohepatitis, MDB formation occurs in 80% of biopsies (French 1981; French 1981). While previous studies have focused on in vitro cell lines and mouse models, we are the first group to investigate inflammasome activation in AH liver biopsy specimen and correlate it with MDB formation. Expression of NOD1, NLRP3, ASC, NAIP, MAVS, caspase 1, IL-1?, IL-18, and other inflammatory components including IL-6, IL-10, TNF-?, IFN-?, STAT3, and p65 was measured in three to eight formalin-fixed paraffin-embedded AH specimens and control normal liver specimens by immunofluorescence staining and quantified by immunofluorescence intensity. The specimens were double stained with ubiquitin to demonstrate the relationship between inflammasome activation and MDB formation. MAVS, caspase1, IL-18, and TNF-? showed increases in expression in AH compared to the controls (p<0.05), and NAIP expression markedly increased in AH compared to the controls (p<0.01). There was a trend that levels of NLRP3, ASC, caspase1, IL-18, IL-10, and p65 expression correlated with the number of MDBs found in the same field of measurement (correlation coefficients were between 0.62 and 0.93, p<0.05). Our results demonstrate the activation of the inflammasome in AH and suggest that MDB could be an indicator of the extent of inflammasome activation. PMID:25149528

Peng, Yue; French, Barbara A; Tillman, Brittany; Morgan, Timothy R; French, Samuel W

2014-10-01

190

Alcohol  

MedlinePLUS

... Text Size: A A A Listen En Español Alcohol Wondering if alcohol is off limits with diabetes? Most people with diabetes can have a moderate amount of alcohol. Research has shown that there can be some ...

191

Alcohol  

MedlinePLUS

If you are like many Americans, you drink alcohol at least occasionally. For many people, moderate drinking ... risky. Heavy drinking can lead to alcoholism and alcohol abuse, as well as injuries, liver disease, heart ...

192

Post?load insulin resistance is an independent predictor of hepatic fibrosis in virus C chronic hepatitis and in non?alcoholic fatty liver disease  

PubMed Central

Background Insulin resistance is a significant risk factor for hepatic fibrosis in patients with both non?alcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC), either directly or by favouring hepatic steatosis. Several methods are available to assess insulin resistance, but their impact on this issue has never been evaluated. Aims To determine the relative contribution of steatosis, metabolic abnormalities and insulin resistance, measured by different basal and post?load parameters, to hepatic fibrosis in CHC and in NAFLD patients. Methods In 90 patients with CHC and 90 pair?matched patients with NAFLD, the degree of basal insulin resistance (by the homeostasis model assessment, (HOMA)) and post?load insulin sensitivity (by the oral glucose insulin sensitivity (OGIS) index) was assessed, together with the features of the metabolic syndrome according to Adult Treatment Panel III definition. Data were correlated with hepatic histopathology. Results The prevalence of basal insulin resistance (HOMA values >75th percentile of normal) was 23.3% in CHC patients and 57.8% in NAFLD, but it increased to 28.8 and 67.8% when measured by post?load insulin resistance (OGIS <25th percentile). In a multivariate model, after adjustment for age, gender and body mass index, OGIS was a predictor of severe fibrosis in CHC and in NAFLD patients, independently of steatosis. An OGIS value below the cut?off of the 25th percentile increased the likelihood ratio of severe fibrosis by a factor of 1.5–2 and proved to be a more sensitive and generally more specific test than HOMA?R for the identification of subjects with severe fibrosis both in NAFLD and in CHC. Conclusions Post?load insulin resistance (OGIS <9.8?mg/kg/min) is associated with severe hepatic fibrosis in both NAFLD and CHC patients, and may help identify subjects at risk of progressive disease. PMID:17392334

Svegliati?Baroni, G; Bugianesi, E; Bouserhal, T; Marini, F; Ridolfi, F; Tarsetti, F; Ancarani, F; Petrelli, E; Peruzzi, E; Cascio, M Lo; Rizzetto, M; Marchesini, G; Benedetti, A

2007-01-01

193

Protective Effect of N-Acetylserotonin against Acute Hepatic Ischemia-Reperfusion Injury in Mice  

PubMed Central

The purpose of this study was to investigate the possible protective effect of N-acetylserotonin (NAS) against acute hepatic ischemia-reperfusion (I/R) injury in mice. Adult male mice were randomly divided into three groups: sham, I/R, and I/R + NAS. The hepatic I/R injury model was generated by clamping the hepatic artery, portal vein, and common bile duct with a microvascular bulldog clamp for 30 min, and then removing the clamp and allowing reperfusion for 6 h. Morphologic changes and hepatocyte apoptosis were evaluated by hematoxylin-eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, respectively. Activated caspase-3 expression was evaluated by immunohistochemistry and Western blot. The activation of aspartate aminotransferase (AST), malondialdehyde (MDA), and superoxide dismutase (SOD) was evaluated by enzyme-linked immunosorbent assay (ELISA). The data show that NAS rescued hepatocyte morphological damage and dysfunction, decreased the number of apoptotic hepatocytes, and reduced caspase-3 activation. Our work demonstrates that NAS ameliorates hepatic IR injury. PMID:23994834

Yu, Shuna; Zheng, Jie; Jiang, Zhengchen; Shi, Caixing; Li, Jin; Du, Xiaodong; Wang, Hailiang; Jiang, Jiying; Wang, Xin

2013-01-01

194

The microbiota regulates susceptibility to Fas-mediated acute hepatic injury.  

PubMed

Whereas a significant role for intestinal microbiota in affecting the pathogenesis and progression of chronic hepatic diseases is well documented, the contribution of the intestinal flora to acute liver injury has not been extensively addressed. Elucidating the influence of the intestinal microbiota on acute liver inflammation would be important for better understanding the transition from acute injury to chronic liver disease. Using the Concanavalin A (ConA)-induced liver injury model in laboratory mice, we show that the severity of acute hepatic damage varies greatly among genetically identical mice raised in different environments and harboring distinct microbiota. Through reconstitution of germ-free (GF) mice, and the co-housing of conventional mice, we provide direct evidence that manipulation of the intestinal flora alters susceptibility to ConA-induced liver injury. Through deep sequencing of the fecal microbiome, we observe that the relative abundance of Ruminococcaceae, a Gram(+) family within the class Clostridia, but distinct from segmented filamentous bacteria, is positively associated with the degree of liver damage. Searching for the underlying mechanism(s) that regulate susceptibility to ConA, we provide evidence that the extent of liver injury following triggering of the death receptor Fas varies greatly as a function of the microbiota. We demonstrate that the extent of Fas-induced liver injury increases in GF mice after microbiota reconstitution, and decreases in conventionally raised mice following reduction in intestinal bacterial load, by antibiotic treatment. We also show that the regulation of sensitivity to Fas-induced liver injury is dependent upon the toll-like receptor signaling molecule MyD88. In conclusion, the status and composition of the intestinal microbiota determine the susceptibility to ConA-induced acute liver injury. The microbiota acts as a rheostat, actively modulating the extent of liver damage in response to Fas triggering. PMID:25068658

Celaj, Stela; Gleeson, Michael W; Deng, Jie; O'Toole, George A; Hampton, Thomas H; Toft, Martin F; Morrison, Hilary G; Sogin, Mitchell L; Putra, Juan; Suriawinata, Arief A; Gorham, James D

2014-09-01

195

Spontaneous Evolution in Bilirubin Levels Predicts Liver-Related Mortality in Patients with Alcoholic Hepatitis  

PubMed Central

The accurate prognostic stratification of alcoholic hepatitis (AH) is essential for individualized therapeutic decisions. The aim of this study was to develop a new prognostic model to predict liver-related mortality in Asian AH patients. We conducted a hospital-based, retrospective cohort study using 308 patients with AH between 1999 and 2011 (a derivation cohort) and 106 patients with AH between 2005 and 2012 (a validation cohort). The Cox proportional hazards model was constructed to select significant predictors of liver-related death from the derivation cohort. A new prognostic model was internally validated using a bootstrap sampling method. The discriminative performance of this new model was compared with those of other prognostic models using a concordance index in the validation cohort. Bilirubin, prothrombin time, creatinine, potassium at admission, and a spontaneous change in bilirubin levels from day 0 to day 7 (SCBL) were incorporated into a model for AH to grade the severity in an Asian patient cohort (MAGIC). For risk stratification, four risk groups were identified with cutoff scores of 29, 37, and 46 based on the different survival probabilities (P<0.001). In addition, MAGIC showed better discriminative performance for liver-related mortality than any other scoring system in the validation cohort. MAGIC can accurately predict liver-related mortality in Asian patients hospitalized for AH. Therefore, SCBL may help us decide whether patients with AH urgently require corticosteroid treatment. PMID:25013906

Lee, Minjong; Kim, Won; Choi, Yunhee; Kim, Sunhee; Kim, Donghee; Yu, Su Jong; Lee, Jeong-Hoon; Kim, Hwi Young; Jung, Yong Jin; Kim, Byeong Gwan; Kim, Yoon Jun; Yoon, Jung-Hwan; Lee, Kook Lae; Lee, Hyo-Suk

2014-01-01

196

Alcoholic liver disease  

MedlinePLUS

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

197

[Bleeding gastric ulcers and acute hepatitis: 2 simultaneous adverse reactions due to nimesulide in a case].  

PubMed

A 66 year-old obese woman with arthrosis, self-medicated with oral nimesulide, 200 mg daily. After 6 weeks she developed nausea, jaundice and dark urine. Two weeks later she had recurrent hematemesis and was hospitalized. Besides obesity and anemia her physical examination was unremarkable. An upper GI endoscopy revealed 3 acute gastric ulcers and a 4th one in the pyloric channel. Abdominal ultrasonogram showed a slightly enlarged liver with diffuse reduction in ecogenicity; the gallbladder and biliary tract were normal. Blood tests demonstrated a conjugated hyperbilirubinemia (maximal total value: 18.4 mg/dl), ALAT 960 U/l, ASAT 850 U/l, GGT 420 U/l, alkaline phosphatases mildly elevated, pro-time 49% and albumin 2.7 mg/dl. Serum markers for hepatitis A, B and C viruses were negative. ANA, AMA, anti-SmA, were negative. Ceruloplasmin was normal. A liver biopsy showed bridging necrosis and other signs of acute toxic liver damage. Gastric ulcers healed after conventional treatment and hepatitis subsided after 2 months leaving no signs of chronic liver damage. The diagnosis of toxic hepatitis due to nimesulide was supported by the time-course of drug usage, sex, age, absence of other causes of liver disease, a compatible liver biopsy and the improvement after drug withdrawal. Peptic ulcers or toxic hepatitis have been previously described as independent adverse reactions in patients taking nimesulide or other NSAIDs but their simultaneous occurrence in a single patient is a unique event that deserves to be reported. PMID:11227244

Tejos, S; Torrejón, N; Reyes, H; Meneses, M

2000-12-01

198

TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non-alcoholic fatty liver disease  

PubMed Central

Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition, strongly associated with the metabolic syndrome, that can lead to progressive hepatic fibrosis, cirrhosis and hepatic failure. Subtle inter-patient genetic variation and environmental factors combine to determine variation in disease progression. A common non-synonymous polymorphism in TM6SF2 (rs58542926 c.449 C>T, p.Glu167Lys) was recently associated with increased hepatic triglyceride content, but whether this variant promotes clinically relevant hepatic fibrosis is unknown. Here we confirm that TM6SF2 minor allele carriage is associated with NAFLD and is causally related to a previously reported chromosome 19 GWAS signal that was ascribed to the gene NCAN. Furthermore, using two histologically characterized cohorts encompassing steatosis, steatohepatitis, fibrosis and cirrhosis (combined n=1,074), we demonstrate a new association, independent of potential confounding factors (age, BMI, type 2 diabetes mellitus and PNPLA3 rs738409 genotype), with advanced hepatic fibrosis/cirrhosis. These findings establish new and important clinical relevance to TM6SF2 in NAFLD. PMID:24978903

Liu, Yang-Lin; Reeves, Helen L.; Burt, Alastair D.; Tiniakos, Dina; McPherson, Stuart; Leathart, Julian B. S.; Allison, Michael E. D.; Alexander, Graeme J.; Piguet, Anne-Christine; Anty, Rodolphe; Donaldson, Peter; Aithal, Guruprasad P.; Francque, Sven; Van Gaal, Luc; Clement, Karine; Ratziu, Vlad; Dufour, Jean-Francois; Day, Christopher P.; Daly, Ann K.; Anstee, Quentin M.

2014-01-01

199

Acute hepatitis in a woman following excessive ingestion of an energy drink: a case report  

PubMed Central

Introduction The consumption of energy drinks has increased significantly. We report the case of a patient who presented to our hospital with jaundice, abdominal pain, and markedly increased liver transaminases likely due to the increased consumption of an energy drink. To the best of our knowledge, this is the first case report in the literature linking the development of acute hepatitis to the consumption of an energy drink. Case presentation A 22-year-old Caucasian woman presented to our hospital with epigastric pain, nausea, vomiting, and low-grade fever. She had been drinking 10 cans of an energy drink daily for two weeks prior to presentation. Her physical examination revealed mild epigastric tenderness. Her initial blood tests revealed elevated alanine aminotransferase, aspartate aminotransferase, and total bilirubin. A computed tomographic scan of the abdomen and pelvis was normal, and the patient was discharged to home. She returned to the Emergency Department of our hospital with worsening pain and new-onset jaundice. This time her physical examination revealed epigastric tenderness and icteric sclera. Her aspartate aminotransferase, alanine aminotransferase, and international normalized ratio were markedly elevated. Further radiological studies were non-specific, and she was admitted to our hospital with a diagnosis of acute hepatitis. Her viral serology and toxicology screens were negative. The patient was treated supportively and was discharged after resolution of her symptoms and a marked decrease in her liver enzymes. Conclusion The development of acute hepatitis in this patient was most likely due to the excessive ingestion of an energy drink, and we speculate that niacin was the culprit ingredient. PMID:21696583

2011-01-01

200

Oral administration of sepimostat mesilate prevents acute alcohol pancreatic injury in rats.  

PubMed

The preventive effect of a novel synthetic serine protease inhibitor, sepimostat mesilate (sepimostat), on acute alcohol pancreatic injury, induced by exocrine hyperstimulation and ethanol administration, was assessed and compared with that of a similar protease inhibitor, camostat mesilate (camostat). Conscious rats were infused with 1 microg mL(-1) h(-1) caerulein intravenously for 6 h and with 0.1 g mL(-1) h(-1) ethanol for 9 h, with the latter infusion beginning 3 h after the start of the caerulein infusion. Sepimostat or camostat was administered orally 1 h before the caerulein infusion. Rats infused with caerulein plus ethanol showed increased plasma amylase and lipase activities, and aggravated pancreatic interstitial oedema when compared with rats given caerulein alone. Sepimostat at 10 and 30 mg kg(-1) prevented the increase in plasma amylase and lipase activities caused by caerulein plus ethanol infusion. Sepimostat at 30 mg kg(-1) suppressed the histological change. Camostat did not show any preventive effects at the equivalent dose. When conscious rats were infused with 1 microg mL(-1) h(-1) caerulein alone intravenously for 6 h, plasma amylase and lipase activities were increased compared with rats given saline. Neither drug prevented the increase in these activities at 30mg kg(-1). Our results suggest that sepimostat has superior preventive effects on alcohol-induced acute pancreatic injury compared with camostat. Sepimostat may thus be a useful drug in the therapy of alcohol-induced pancreatitis. PMID:10467964

Yuasa, C; Irimura, K; Oda, M; Fukui, K; Oka, T

1999-07-01

201

The effect of acute alcohol intoxication on gut wall integrity in healthy male volunteers; a randomized controlled trial.  

PubMed

The aim of the study is to determine the effect of acute alcohol consumption on enterocytes. Chronic alcohol consumption has been known to induce a decrease in gut wall integrity in actively drinking alcoholics and patients with alcohol-induced liver disease. Data on the extent of the damage induced by acute alcohol consumption in healthy human beings is scarce. Studies show that heavy incidental alcohol consumption is a growing problem in modern society. Data on this matter may provide insights into the consequences of this behavior for healthy individuals. In a randomized clinical trial in crossover design, 15 healthy volunteers consumed water one day and alcohol the other. One blood sample was collected pre-consumption, five every hour post-consumption, and one after 24 h. Intestinal fatty acid binding protein (I-FABP) was used as a marker for enterocyte damage. Liver fatty acid binding protein (L-FABP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) were used as markers for hepatocyte damage. Lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) were used as a measure of translocation. Interleukin-6 (IL-6) was used to assess the acute inflammatory response to endotoxemia. Alcohol consumption caused a significant increase in serum I- and L-FABP levels, compared to water consumption. Levels increased directly post-consumption and decreased to normal levels within 4 h. LBP, sCD14, and IL-6 levels were not significantly higher in the alcohol group. Moderate acute alcohol consumption immediately damages the enterocyte but does not seem to cause endotoxemia. PMID:25559494

de Jong, W J; Cleveringa, A M; Greijdanus, B; Meyer, P; Heineman, E; Hulscher, J B

2015-02-01

202

[Effect of plant preparations on lipid peroxidation parameters in acute toxic hepatitis].  

PubMed

The influence of the original vegetable complexes (which include: juices of beet-rout and carrot, decoction of degrose berries, extracts of corn silk, leaves of peppermint and some other components) on the indicators of the cytolysis, lipid peroxidation and antioxidant system of serum of the laboratory rats with acute toxic hepatitis, was investigated. The vegetable complexes exhibited antioxidant effects which were proved by the reduction of the final and intermediate products of lipoperoxidization, the absence of decline of the level of endogenous alpha-tocopherol content and glutathione dependent enzymes. PMID:11925749

Katikova, O Iu; Kostin, Ia V; Iagudina, R I; Tishkin, V S

2001-01-01

203

Effects of acute alcohol intoxication on saccadic conflict and error processing  

PubMed Central

Rationale Flexible behavior optimization relies on cognitive control which includes the ability to suppress automatic responses interfering with relevant goals. Extensive evidence suggests that the anterior cingulate cortex (ACC) is the central node in a predominantly frontal cortical network subserving executive tasks. Neuroimaging studies indicate that the ACC is sensitive to acute intoxication during conflict, but such evidence is limited to tasks using manual responses with arbitrary response contingencies. Objectives The present study was designed to examine whether alcohol's effects on top–down cognitive control would generalize to the oculomotor system during inhibition of hardwired saccadic responses. Methods Healthy social drinkers (N=22) underwent functional magnetic resonance imaging (fMRI) scanning and eye movement tracking during alcohol (0.6 g/kg ethanol for men, 0.55 g/kg for women) and placebo conditions in a counterbalanced design. They performed visually guided prosaccades (PS) towards a target and volitional antisaccades (AS) away from it. To mitigate possible vasoactive effects of alcohol on the BOLD (blood oxygenation level-dependent) signal, resting perfusion was quantified with arterial spin labeling (ASL) and used as a covariate in the BOLD analysis. Results Saccadic conflict was subserved by a distributed frontoparietal network. However, alcohol intoxication selectively attenuated activity only in the ACC to volitional AS and erroneous responses. Conclusions This study provides converging evidence for the selective ACC vulnerability to alcohol intoxication during conflict across different response modalities and executive tasks, confirming its supramodal, high-level role in cognitive control. Alcohol intoxication may impair top–down regulative functions by attenuating the ACC activity, resulting in behavioral disinhibition and decreased self-control. PMID:23812762

Rickenbacher, Elizabeth; Azma, Sheeva; Artsy, Elinor; Lee, Adrian K. C.

2013-01-01

204

Alcoholism  

Microsoft Academic Search

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

James C. Garbutt

205

Molecular epidemiology of hepatitis B virus genotypes circulating in acute hepatitis B patients in the Campania region.  

PubMed

Fifty-three HBV-DNA-positive patients with symptomatic acute hepatitis B were enrolled from 1999 to 2010 to evaluate molecular and phylogenetic changes in HBV in southern Italy. HBV polymerase region was evaluated by direct sequencing in plasma samples obtained at first observation. Different data sets were aligned and a phylogenetic tree was inferred using PhyML program. Statistical robustness was confirmed with a bootstrap analysis. A Bayesian Markov chain Monte Carlo method and a Bayesian skyline plot were used to estimate the evolution of our samples. The dN/dS rate (?) was estimated by the maximum likelihood approach to investigate the presence of codons under positive selection. The MacClade program was used to test viral gene out/in flow only among HBV-D3 subgenotype patients with different risk factors. Of the 53 patients, 83% were born in Italy and 17% were foreigners. HBV genotype D was prevalent (64.1%), followed by genotype A (26.4%), E (3.8%), and F (5.7%). The prevalent subgenotype was D3 (70.6%). The Bayesian tree of the 24 D3 subgenotypes showed two main clades both dated 1994; 40% of viral gene flow observed was from intravenous drugs users and heterosexual patients. Phylogenetic analysis of HBV isolates showed that HBV-D3 remains the prevalent genotype, but also subgenotype A2 has become frequent in southern Italy. This may be of clinical relevance in years to come, since patients with HBV-genotype-A chronic infection less frequently than those with genotype D develop HBeAg-negative chronic hepatitis and respond more frequently to alfa-interferon treatment. PMID:24980631

Sagnelli, Caterina; Ciccozzi, Massimo; Pisaturo, Mariantonietta; Zehender, Gianguglielmo; Lo Presti, Alessandra; Alessio, Loredana; Starace, Mario; Lovero, Domenica; Sagnelli, Evangelista; Coppola, Nicola

2014-10-01

206

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

PubMed

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

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

2013-01-01

207

Assessing Candidacy for Acute Hepatitis C Treatment Among Active Young Injection Drug Users: A Case-Series Report  

PubMed Central

Treatment for acute hepatitis C virus (HCV) infection has significantly better outcomes than treatment for chronic infection. The short window of the acute period poses challenges for young injection drug users (IDU), who are at highest risk of HCV infection, to demonstrate treatment candidacy. We recruited patients with acute HCV from a prospective cohort study to examine clinical and behavioral issues related to treatment candidacy. We report on outcomes and how nursing case management affected candidacy. All 5 acutely-infected participants reported daily drug use at baseline. All established primary care and decreased their drug use. None received treatment for their acute infection; one was treated within 12 months of infection. . Establishing treatment candidacy for young IDU in the acute phase involves various health domains. Acute infection's short period poses many challenges to establishing candidacy, but it is a window of opportunity to engage young IDU in health care. PMID:21497111

Asher, Alice; Lum, Paula J.; Page, Kimberly

2011-01-01

208

Assessing candidacy for acute hepatitis C treatment among active young injection drug users: a case-series report.  

PubMed

Treatment for acute hepatitis C virus (HCV) infection has significantly better outcomes than treatment for chronic infection. The short window of the acute period poses challenges for young injection drug users (IDU), who are at highest risk of HCV infection, to demonstrate treatment candidacy. We recruited patients with acute HCV from a prospective cohort study to examine clinical and behavioral issues related to treatment candidacy. We report on outcomes and how nursing case management affected candidacy. All five acutely-infected participants reported daily drug use at baseline. All established primary care and decreased their drug use. None received treatment for their acute infection; one was treated within 12 months of infection. Establishing treatment candidacy for young IDU in the acute phase involves various health domains. An acute infection's short period poses many challenges to establishing candidacy, but it is a window of opportunity to engage young IDU in health care. PMID:21497111

Asher, Alice; Lum, Paula J; Page, Kimberly

2012-01-01

209

Delta agent (Hepatitis D)  

MedlinePLUS

... is found only in people who carry the hepatitis B virus. HDV may make a recent (acute) hepatitis B ... can even cause symptoms in people who carry hepatitis B virus but who never had symptoms. Hepatitis D infects ...

210

Protective Effect of Emblica officinalis Against Alcohol-Induced Hepatic Injury by Ameliorating Oxidative Stress in Rats  

PubMed Central

The effect of Emblica officinalis fruit extract (EFE) against alcohol-induced hepatic damage in rats was investigated in the present study. In vitro studies showed that EFE possesses antioxidant as well nitric oxide (NO) scavenging activity. In vivo administration of alcohol (5 g/kg b.wt/day) for 60 days resulted increased liver lipid peroxidation, protein carbonyls, nitrite plus nitrate levels. Alcohol administration also significantly lowers the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and reduced glutathione as compared with control rats. Administration of EFE (250 mg/kg body weight) to alcoholic rats significantly brought the plasma enzymes towards near normal level and also significantly reduced the levels of lipid peroxidation, protein carbonyls and restored the enzymic and non-enzymatic antioxidants level. This observation was supplemented by histopathological examination in liver. Our data indicate that the tannoid, flavonoid and NO scavenging compounds present in EFE may offer protection against free radical mediated oxidative stress in rat hepatocytes of animals with alcohol-induced liver injury. PMID:21966117

Damodara Reddy, V.; Padmavathi, P.; Gopi, S.; Paramahamsa, M.

2010-01-01

211

Necro-inflammatory response of pancreatic acinar cells in the pathogenesis of acute alcoholic pancreatitis  

PubMed Central

The role of pancreatic acinar cells in initiating necro-inflammatory responses during the early onset of alcoholic acute pancreatitis (AP) has not been fully evaluated. We investigated the ability of acinar cells to generate pro- and anti-inflammatory mediators, including inflammasome-associated IL-18/caspase-1, and evaluated acinar cell necrosis in an animal model of AP and human samples. Rats were fed either an ethanol-containing or control diet for 14 weeks and killed 3 or 24?h after a single lipopolysaccharide (LPS) injection. Inflammasome components and necro-inflammation were evaluated in acinar cells by immunofluorescence (IF), histology, and biochemical approaches. Alcohol exposure enhanced acinar cell-specific production of TNF?, IL-6, MCP-1 and IL-10, as early as 3?h after LPS, whereas IL-18 and caspase-1 were evident 24?h later. Alcohol enhanced LPS-induced TNF? expression, whereas blockade of LPS signaling diminished TNF? production in vitro, indicating that the response of pancreatic acinar cells to LPS is similar to that of immune cells. Similar results were observed from acinar cells in samples from patients with acute/recurrent pancreatitis. Although morphologic examination of sub-clinical AP showed no visible signs of necrosis, early loss of pancreatic HMGB1 and increased systemic levels of HMGB1 and LDH were observed, indicating that this strong systemic inflammatory response is associated with little pancreatic necrosis. These results suggest that TLR-4-positive acinar cells respond to LPS by activating the inflammasome and producing pro- and anti-inflammatory mediators during the development of mild, sub-clinical AP, and that these effects are exacerbated by alcohol injury. PMID:24091659

Gu, H; Werner, J; Bergmann, F; Whitcomb, D C; Büchler, M W; Fortunato, F

2013-01-01

212

Zinc mesoporphyrin represses induced hepatic 5-aminolevulinic acid synthase and reduces heme oxygenase activity in a mouse model of acute hepatic porphyria.  

PubMed

Zinc mesoporphyrin (ZnMP) is a potent inhibitor of heme oxygenase (HO) and represses 5-aminolevulinic acid synthase (ALAS). These properties make it a potential candidate for treatment of inducible acute hepatic porphyrias, diseases characterized by neurovisceral symptoms, and massive ALAS induction. Effects of intraperitoneal ZnMP (2.5-10 micromol/kg/d) and heme arginate (3-6 mg/kg/d) on plasma levels of 5-aminolevulinic acid (ALA), on messenger RNA (mRNA), and activity of hepatic ALAS and HO were studied in porphobilinogen deaminase-deficient mice treated with phenobarbital (100 mg/kg/d) to induce ALAS. ZnMP (5 micromol/kg/d) led to a significant reduction of plasma ALA levels to 31% of controls (P < .01) by lowering the activity of hepatic mitochondrial and cytosolic ALAS to 29% and 25% of controls, respectively (P < .03). ZnMP decreased the mRNA levels of hepatic ALAS to 53% (P < .03) of controls and this repression was more pronounced than that achieved with heme arginate. In contrast to heme arginate, ZnMP led to a significant reduction of HO activity. We conclude that the combined effect of ZnMP on highly induced ALAS and on HO may be of potential benefit for human acute hepatic porphyrias and therefore merits further in vivo investigations addressing questions raised by this study. PMID:11343251

Schuurmans, M M; Hoffmann, F; Lindberg, R L; Meyer, U A

2001-05-01

213

Acute Marchiafava-Bignami disease presenting as reversible dementia in a chronic alcoholic  

PubMed Central

Marchiafava-Bignami disease (MBD) is a rare complication of chronic alcoholism. Its clinical diagnosis has considerably changed during recent times, with MRI of the brain paving way for in life diagnosis. We believe that physicians need to have a high index of suspicion, because acute onset MBD is not always fatal and complete recovery is possible, provided the diagnosis is made early and treated appropriately. We report a case of MBD who was diagnosed early in the disease course with subsequent clinical and radiological recovery on institution of appropriate treatment. PMID:23417939

Sehgal, Vineet; Kesav, Praveen; Modi, M; Ahuja, Chirag K

2013-01-01

214

Rapid spontaneous resolution of acute subdural haematoma in a patient with chronic alcoholism.  

PubMed

Acute subdural haematoma (ASDH) constitutes one of the most critical emergencies in neurosurgery. There are only several reports that show the rapid disappearance of ASDH without surgical intervention. We report a case of a 64-year-old alcoholic man who had a traumatic subdural haematoma after a fall from a height of about eight meters on level ground. The computed tomography (CT) of the brain on admission demonstrated a left parietooccipital ASDH. A follow-up CT scan after 8 hours showed resolution of the hematoma. The patient was discharged 9 days later with no neurological deficit. We discuss the possible mechanisms of the rapid resolution of the ASDH. PMID:22111954

Hadjigeorgiou, Georgios; Chamilos, Christos; Petsanas, Adamantios; Vranos, Georgios; Foteas, Pavlos; Spiridakis, Filokypros

2012-06-01

215

CD8+?T-Cell Responses in Acute Hepatitis C Virus Infection  

PubMed Central

Hepatitis C virus (HCV) infects approximately 170 million people worldwide and is a major cause of life-threatening liver diseases such as liver cirrhosis and hepatocellular carcinoma. Acute HCV infection often progresses to chronic persistent infection, although some patients recover spontaneously. The divergent outcomes of acute HCV infection are known to be determined by differences in virus-specific T-cell responses among patients. Of the two major T-cell subsets, CD8+ T-cells are known to be the key effector cells that control viral infections via cytolytic activity and cytokine secretion. Herein, we review various aspects of HCV-specific CD8+ T-cell responses in acute HCV infection. In particular, we focus on timing of CD8+ T-cell responses, relationship between CD8+ T-cell responses and outcomes of acute HCV infection, receptor expression on CD8+ T-cells, breadth of CD8+ T-cell responses, and viral mutations. PMID:24936203

Sung, Pil Soo; Racanelli, Vito; Shin, Eui-Cheol

2014-01-01

216

The role of chemokines in acute and chronic hepatitis C infection  

PubMed Central

Hepatitis C imposes a significant burden on global healthcare. Chronic infection is associated with progressive inflammation of the liver which typically manifests in cirrhosis, organ failure and cancer. By virtue of elaborate evasion strategies, hepatitis C virus (HCV) succeeds as a persistent human virus. It has an extraordinary capacity to subvert the immune response enabling it to establish chronic infections and associated liver disease. Chemokines are low molecular weight chemotactic peptides that mediate the recruitment of inflammatory cells into tissues and back into the lymphatics and peripheral blood. Thus, they are central to the temporal and spatial distribution of effector and regulatory immune cells. The interactions between chemokines and their cognate receptors help shape the immune response and therefore, have a major influence on the outcome of infection. However, chemokines represent a target for modulation by viruses including the HCV. HCV is known to modulate chemokine expression in vitro and may therefore enable its survival by subverting the immune response in vivo through altered leukocyte chemotaxis resulting in impaired viral clearance and the establishment of chronic low-grade inflammation. In this review, the roles of chemokines in acute and chronic HCV infection are described with a particular emphasis placed on chemokine modulation as a means of immune subversion. We provide an in depth discussion of the part played by chemokines in mediating hepatic fibrosis while addressing the potential applications for these chemoattractants in prognostic medicine. PMID:23954947

Fahey, Stephen; Dempsey, Eugene; Long, Aideen

2014-01-01

217

Use of linear and multiple antigenic peptides in the immunodiagnosis of acute hepatitis A virus infection.  

PubMed

The reactivities of two panels of anti-HAV human sera from geographically distinct areas (Chile and Spain) to synthetic peptides from the VP1, VP2 and VP3 hepatitis A virus capsid proteins were examined by an enzyme-linked immunosorbent assay (ELISA) procedure. Two and four branched multiple antigenic peptides (MAPs) and palmitoylated peptides were compared with free synthetic sequences for the detection of IgM anti-HAV antibodies in the two panels of human sera. Our results showed that acute hepatitis A patient sera recognized preferentially homogeneous two branched MAPs and palmitic acid conjugated peptides. The palmitoyl-derived VP3(110-121) peptide and the corresponding dimeric MAP were the most sensitive and appropriate for serological studies of HAV-infected patients by ELISA, sensitivity and specificity being higher than 90% and 95%, respectively. These peptide-based tests open up new avenues in the development of peptide-based immunosorbent assays for the detection of acute HAV disease. PMID:10669766

Gómara, M J; Riedemann, S; Vega, I; Ibarra, H; Ercilla, G; Haro, I

2000-02-01

218

Clinical, histologic and serologic evaluation of patients with acute non-A-E hepatitis in north-eastern Brazil: is it an infectious disease?  

Microsoft Academic Search

Non-A-E hepatitis and acute cryptogenic hepatitis are the names given to the disease of patients with clinical hepatitis, but in whom serologic evidence of A-E hepatitis has not been found. Over a period of 8 years, we evaluated in Brazil 32 patients who fulfilled the criteria for this diagnosis in order to determine patterns of the clinical illness, laboratory parameters,

Raymundo Paraná; Zilton Andrade; Luiz A. R. de Freitas; Rogério Santos-Jesus; Mitermayer Reis; Helma Cotrim; Simone Cunha; Christian Trepo

2003-01-01

219

Alcohol  

MedlinePLUS

... are fermented . Fermentation is a process that uses yeast or bacteria to change the sugars in the ... parents and other adults use alcohol socially — having beer or wine with dinner, for example — alcohol seems ...

220

Ethylene-vinyl alcohol copolymer endobiliary obliteration of hepatic segments in a patient with isolated bile leaks.  

PubMed

A 54-year-old woman with a symptomatic giant hepatic hemangioma underwent an extended left hepatic trisegmentectomy complicated by 250-350 mL/d postoperative bilious drainage. After 5 months of therapy, drainage was unabated, and the patient was no longer a surgical candidate. Sinography revealed three distinct isolated bile duct leaks involving segments 6, 7, and 8. Endobiliary segmentectomy was achieved by obliterating the isolated systems with ethylene-vinyl alcohol copolymer (Onyx; ev3, Plymouth, Minnesota) during three fluoroscopic procedures. Bilious leaks were successfully eliminated, and compensatory hypertrophy of noninvolved liver occurred. At 2 years from the last embolization procedure, the patient remained asymptomatic with no bilious leak. PMID:25442143

Wible, Brandt C; Gooden, Christie; Saucier, Nathan; Borsa, John J; Cummings, Lee S; Cho, Kenneth H

2014-11-01

221

Alcohol  

MedlinePLUS

... Body Works Main Page The Pink Locker Society Alcohol KidsHealth > Kids > Staying Healthy > Being Good to My Body > Alcohol Print A A A Text Size What's in ... fun." "It's cool. Everybody drinks, right?" Wrong. Drinking alcohol is dangerous for kids and teens and sometimes ...

222

Dietary fat sources differentially modulate intestinal barrier and hepatic inflammation in alcohol-induced liver injury in rats  

PubMed Central

Endotoxemia is a causal factor in the development of alcoholic liver injury. The present study aimed at determining the interactions of ethanol with different fat sources at the gut-liver axis. Male Sprague-Dawley rats were pair fed control or ethanol liquid diet for 8 wk. The liquid diets were based on a modified Lieber-DeCarli formula, with 30% total calories derived from corn oil (rich in polyunsaturated fatty acids). To test the effects of saturated fats, corn oil in the ethanol diet was replaced by either cocoa butter (CB, rich in long-chain saturated fatty acids) or medium-chain triglycerides (MCT, exclusively medium-chain saturated fatty acids). Ethanol feeding increased hepatic lipid accumulation and inflammatory cell infiltration and perturbed hepatic and serum metabolite profiles. Ethanol feeding with CB or MCT alleviated ethanol-induced liver injury and attenuated ethanol-induced metabolic perturbation. Both CB and MCT also normalized ethanol-induced hepatic macrophage activation, cytokine expression, and neutrophil infiltration. Ethanol feeding elevated serum endotoxin level, which was normalized by MCT but not CB. In accordance, ethanol-induced downregulations of intestinal occludin and zonula occludens-1 were normalized by MCT but not CB. However, CB normalized ethanol-increased hepatic endotoxin level in association with upregulation of an endotoxin detoxifying enzyme, argininosuccinate synthase 1 (ASS1). Knockdown ASS1 in H4IIEC3 cells resulted in impaired endotoxin clearance and upregulated cytokine expression. These data demonstrate that the protection of saturated fats against alcohol-induced liver injury occur via different actions at the gut-liver axis and are chain length dependent. PMID:24113767

Zhong, Wei; Li, Qiong; Xie, Guoxiang; Sun, Xiuhua; Tan, Xiaobing; Sun, Xinguo; Jia, Wei

2013-01-01

223

Rac1 modulates acute and subacute genotoxin-induced hepatic stress responses, fibrosis and liver aging  

PubMed Central

To investigate the importance of the Ras-homologous GTPase Rac1 for the hepatic response to genotoxic insults and liver aging, rac1 was deleted in liver of mice by Mx1-Cre-based recombination. Knockout of rac1 caused complex changes in basal as well as doxorubicin and ionizing radiation-induced mRNA expression of various genotoxic stress response-related genes, including hspa1b, rad51, wrn and xpc. Rac1 deletion protected the liver from acute toxicity following doxorubicin treatment. Moreover, the level of S139 phosphorylated histone H2AX (?H2AX), which is indicative of DNA damage, and mRNA expression of pro-inflammatory (IL-6) and pro-fibrotic (CTGF, TGF?, ?SMA) factors were mitigated in rac1 knockout animals. By contrast, lack of rac1 promoted subacute hepatotoxicity, which was determined 3 weeks after injection of multiple low doses of doxorubicin by assaying the ?H2AX level, mitotic index and pro-fibrotic gene expression. Regarding ionizing radiation, rac1 deficiency had no major effects on DNA damage induction or acute pro-inflammatory and pro-fibrotic stress responses. Mice lacking hepatic rac1 for extended period of time (15 months) revealed increased mRNA expression of fibrosis-related factors (CTGF, TGF?, collagen, MMP1) and fibrotic tissue remodeling. In addition, protein expression of the senescence marker p16 was enhanced in the absence of rac1. Taken together, the data provide evidence that Rac1 is required for doxorubicin-induced DNA damage induction. It is also involved in both the acute and delayed inflammatory and fibrotic stress response in the liver following doxorubicin, but not ionizing radiation, treatment and, furthermore, protects against endogenous liver aging. PMID:23519127

Bopp, A; Wartlick, F; Henninger, C; Kaina, B; Fritz, G

2013-01-01

224

Effect of Curcumin on the Increase in Hepatic or Brain Phosphatidylcholine Hydroperoxide Levels in Mice after Consumption of Excessive Alcohol  

PubMed Central

Curcumin is a bright yellow compound found in Curcuma longa L., a member of the family Zingiberaceae. In the present study, we determined whether curcumin protects against oxidative stress in liver and brain in mice fed excessive alcohol. BALB/c mice were administered 20% alcohol (16?g/kg body weight) with or without curcumin (0.016% in diet) for 12 weeks. The concentrations of phosphatidylcholine hydroperoxide (PC-OOH) in liver and brain samples were determined using chemiluminescence high-performance liquid chromatography. Mice treated with ethanol and curcumin significantly (P < 0.05) showed a lower hepatic PC-OOH level compared to mice treated with only ethanol. However, there was no significant difference in the brain PC-OOH level among all mice. Our finding indicates that the dosage of alcohol might increase the lipid peroxide level of liver but not of brain, and daily curcumin consumption might be protective for liver against alcohol-related oxidative stress in mice. PMID:23607090

Pyun, Chang Won; Han, Kyu-Ho; Hong, Go Eun; Lee, Chi Ho

2013-01-01

225

Greater hepatic vulnerability after alcohol intake in African Americans compared with Caucasians: a population-based study.  

PubMed Central

AIMS OF THE STUDY: In the last 40 years, African Americans have experienced higher age-adjusted liver cirrhosis mortality rates than whites. Alcohol use has been hypothesized to be the likely determinant of this disparity in liver disease mortality. This study was aimed at evaluating racial variations in common biomarkers of liver injury, such as gamma-glutamyltransferase (GGT), aspartate amino transferase (AST) and alanine amino transferase (ALT), by categories of drinking status and levels of current alcohol use. METHODS: A cross-sectional analysis of a general population sample of 3304 residents of Erie and Niagara counties in New York State, 35-80 years of age and free from known hepatic disease, stratified by racial group (African-American and white). RESULTS: Concentrations of GGT were higher for African-Americans than for whites in all categories of drinking status (lifetime abstainers, former and current drinkers) after adjustment for potential confounders (age, sex, education, smoking, and body mass index). However, differences in enzyme mean values between the two racial groups were consistently larger among current drinkers than for either lifetime abstainers or former drinkers. In analyses based on tertiles of alcohol consumption in the last 30 days, differences in GGT mean values between the two races tended to amplify with increasing amounts of consumption. CONCLUSIONS: These findings seem to support the hypothesis of greater sensitivity to alcohol-induced hepatotoxicity among African-Americans than for whites. PMID:15481746

Stranges, Saverio; Freudenheim, Jo L.; Muti, Paola; Farinaro, Eduardo; Russell, Marcia; Nochajski, Thomas H.; Trevisan, Maurizio

2004-01-01

226

Alcohol  

PubMed Central

Suicide is a major public health problem in the United States as well as around the world. The significant role that alcohol plays in suicidality is well known and accepted in the scientific community. The use of alcohol does not necessarily lead to suicide, but through its action and effects, alcohol is an important proximal risk factor for suicidal behavior. There is very little data showing how and why alcohol exerts such tremendous influence and “lubricates the gears” to propel the act of committing suicide. This article will elucidate the complex relationship between alcohol and suicide and how alcohol use can lead to suicide. The article also describes how alcohol affects brain neurophysiology in regards to suicidal behavior. PMID:23440995

Nathani, Milankumar; Jabeen, Shahgufta; Yazdani, Ijlal; Mouton, Charles D.; Bailey, Rahn K.; Mahr, Mona; Pate, Rebecca J.; Riley, Wayne J.

2013-01-01

227

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

PubMed Central

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

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

2013-01-01

228

A Randomized Controlled Trial to Assess the Safety and Efficacy of Silymarin on Symptoms, Signs and Biomarkers of Acute Hepatitis  

PubMed Central

Purpose Milk thistle or its purified extract, silymarin (Silybum marianum), is widely used in treating acute or chronic hepatitis. Although silymarin is hepatoprotective in animal experiments and some human hepatotoxic exposures, its efficacy in ameliorating the symptoms of acute clinical hepatitis remains inconclusive. In this study, our purpose was to determine whether silymarin improves symptoms, signs and laboratory test results in patients with acute clinical hepatitis, regardless of etiology. Methods This is a randomized, placebo-controlled trial in which participants, treating physicians and data management staff were blinded to treatment group. The study was conducted at two fever hospitals in Tanta and Banha, Egypt where patients with symptoms compatible with acute clinical hepatitis and serum alanine aminotransferase (ALT) levels > 2.5 times the upper limit of normal were enrolled. The intervention consisted of three times daily ingestion of either a standard recommended dose of 140 mg of silymarin (Legalon®, MADAUS GmbH, Cologne, Germany), or a vitamin placebo for four weeks with an additional four-week follow-up. The primary outcomes were symptoms and signs of acute hepatitis and results of liver function tests on days 2, 4 and 7 and weeks 2, 4, and 8. Side-effects and adverse events were ascertained by self-report. Results From July 2003 through October 2005, 105 eligible patients were enrolled after providing informed consent. No adverse events were noted and both silymarin and placebo were well tolerated. Patients randomized to the silymarin group had quicker resolution of symptoms related to biliary retention: dark urine (p=0.013), jaundice (p=0.02) and scleral icterus (p=0.043). There was a reduction in indirect bilirubin among those assigned to silymarin (p=0.012), but other variables including direct bilirubin, ALT and aspartate aminotransferase (AST) were not significantly reduced. Conclusions Patients receiving silymarin had earlier improvement in subjective and clinical markers of biliary excretion. Despite a modest sample size and multiple etiologies for acute clinical hepatitis, our results suggest that standard recommended doses of silymarin are safe and may be potentially effective in improving symptoms of acute clinical hepatitis despite lack of a detectable effect on biomarkers of the underlying hepatocellular inflammatory process. PMID:19303273

El-Kamary, Samer S.; Shardell, Michelle D.; Abdel-Hamid, Mohamed; Ismail, Soheir; El-Ateek, Mohamed; Metwally, Mohamed; Mikhail, Nabiel; Hashem, Mohamed; Mousa, Amr; Aboul-Fotouh, Amr; El-Kassas, Mohamed; Esmat, Gamal; Strickland, G. Thomas

2009-01-01

229

Prospective Study of Hepatitis B and C Viral Infections, Cigarette Smoking, Alcohol Consumption, and Other Factors Associated with Hepatocellular Carcinoma Risk in Japan  

Microsoft Academic Search

This community-based prospective study examined the effects of viral infections and lifestyle habits on hepatocellular carcinoma (HCC) risk in Japan. A baseline survey was conducted for 981 males and 2,078 females in June 1992 and evaluated hepatitis B surface antigen, second-generation hepatitis C virus antibody, and history of cigarette smoking and habitual alcohol consumption. By March 1997,14 males and 8

Mitsuru Mori; Megumi Hara; Ikuko Wada; Toshiya Hara; Kyosuke Yamamoto; Morisada Honda; Junichi Naramoto

230

Fulminant hepatic failure and acute renal failure as manifestations of concurrent Q fever and cytomegalovirus infection: a case report.  

PubMed

Background Coxiella burnetii is an obligate bacterial pathogen that causes Q fever. Cytomegalovirus (CMV) commonly exists as a latent infection in healthy people. Co-infection with both pathogens is rare.Case presentationWe report an immunocompetent 53-year-old male farmer who presented with fulminant hepatic failure and acute renal failure. Empiric antibiotic treatment with intravenous penicillin G and levofloxacin were given, but hepatic and renal functions continued to deteriorate. A subsequent test of serum immunoglobulin M was positive for CMV, and administration of gancyclovir led to gradual recovery. A diagnosis of acute Q fever was confirmed by indirect immunofluorescence assay (IFA) on paired serum samples to demonstrate a significant rise in antibody titers. Antibiotic treatment was adjusted accordingly.ConclusionCMV co-infection should be considered in patients with acute Q fever when they do not respond to standard antimicrobial agents. PMID:25487053

Hsu, Jin-Yi; Tsai, Chen-Chi; Tseng, Kuo-Chih

2014-12-01

231

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

PubMed Central

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

Weafer, Jessica

2015-01-01

232

Vitamin B6 metabolism in chronic alcohol abuse The effect of ethanol oxidation on hepatic pyridoxal 5'-phosphate metabolism.  

PubMed Central

Individuals with chronic alcohol abuse frequently exhibit lowered plasma levels of pyridoxal 5'-phosphate, the coenzyme form of vitamin B6. Because the liver is the primary source of this coenzyme in plasma and also the principal organ that oxidizes ethanol, the effect of ethanol on hepatic pyridoxal phosphate metabolism was studied in the rat. The chronic feeding of ethanol (36 percent of the total dietary calories) for 6 wk significantly decreased the hepatic pyridoxal phosphate content both in animals given a sufficient amount of vitamin B6 in their diet and in those rendered vitamin B6 deficient. In isolated perfused livers, the addition of 18 mM ethanol lowered the pyridoxal phosphate content of livers from vitamin B6-sufficient animals and deceased the net synthesis of pyridoxal phosphate from pyridoxine by the livers of vitamin B6-deficient animals. Ethanol also diminished the rate of release of pyridoxal phosphate into the perfusate by the livers of vitamin B6-deficient rats. These effects of ethanol, in vitro, were abolished by 4-methyl pyrazole, an inhibitor of alcohol dehydrogenase. Thus the derangement of pyridoxal phosphate metabolism produced by ethanol is dependt upon its oxidation. These data support previous findings whic indicate that acetaldehyde is the responsible agent which acts by accelerating the degradation of intracellular pyridoxal phosphate. Images PMID:1168205

Vech, R L; Lumeng, L; Li, T K

1975-01-01

233

In vivo relationship between monoamine oxidase type B and alcohol dehydrogenase: effects of ethanol and phenylethylamine  

Microsoft Academic Search

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

S. U. Aliyu; L. Upahi

1988-01-01

234

The role of hepatic fat accumulation in pathogenesis of non-alcoholic fatty liver disease (NAFLD)  

PubMed Central

Nonalcoholic fatty liver disease is increasingly regarded as a hepatic manifestation of metabolic syndrome, and the severity of nonalcoholic fatty liver disease seems to increase in parallel with other features of metabolic syndrome. Excess lipid accumulation in the liver cells is not only a mediator of Metabolic Syndrome and indicator of a lipid overload but also accompanied by a range of histological alterations varying from 'simple' steatosis to nonalcoholic steatohepatitis, with time progressing to manifest cirrhosis. Hepatocellular carcinoma may also occur in nonalcoholic steatohepatitis -related cirrhosis with a mortality rate similar to or worse than for cirrhosis associated with hepatitis C. This review summarizes the knowledge about the causal relationship between hepatic fat accumulation, insulin resistance, liver damage and the etiological role of hepatic fat accumulation in pathogenesis of extra- and intra-hepatic manifestations. Special emphasis is given suggestions of new targets treatment and prevention of nonalcoholic fatty liver disease. PMID:20426802

2010-01-01

235

Hepatitis  

MedlinePLUS

... be serious. Some can lead to scarring, called cirrhosis, or to liver cancer. Sometimes hepatitis goes away by itself. If it does not, it can be treated with drugs. Sometimes hepatitis lasts a lifetime. Vaccines can help prevent some viral forms.

236

Acute rapamycin treatment improved glucose tolerance through inhibition of hepatic gluconeogenesis in rainbow trout (Oncorhynchus mykiss).  

PubMed

Our aim was to investigate the potential role of TOR (target of rapamycin) signaling pathway in the regulation of hepatic glucose metabolism in rainbow trout. Fasted fish were first treated with a single intraperitoneal injection of rapamycin or vehicle and then submitted to a second intraperitoneal administration of glucose 4 h later. Our results revealed that intraperitoneal administration of glucose induced hyperglycemia for both vehicle and rapamycin treatments, which peaked at 2 h. Plasma glucose level in vehicle-treated fish was significantly higher than in rapamycin-treated fish at 8 and 17 h, whereas it remained at the basal level in rapamycin-treated fish. Glucose administration significantly enhanced the phosphorylation of Akt and ribosomal protein S6 kinase (S6K1) in vehicle-treated fish, while rapamycin completely abolished the activation of S6K1 in rapamycin-treated fish, without inhibiting the phosphorylation of Akt on Thr-308 or Ser-473. Despite the lack of significant variation in phosphoenolpyruvate carboxykinase mRNA abundance, mRNA abundance for glucokinase (GK), glucose 6-phosphatase (G6Pase) I and II, and fructose 1,6-bisphosphatase (FBPase) was reduced by rapamycin 17 h after glucose administration. The inhibition effect of rapamycin on GK and FBPase was further substantiated at the activity level. The suppression of GK gene expression and activity by rapamycin provided the first in vivo evidence in fish that glucose regulates hepatic GK gene expression and activity through a TORC1-dependent manner. Unlike in mammals, we observed that acute rapamycin treatment improved glucose tolerance through the inhibition of hepatic gluconeogenesis in rainbow trout. PMID:25163922

Dai, Weiwei; Panserat, Stéphane; Terrier, Frédéric; Seiliez, Iban; Skiba-Cassy, Sandrine

2014-11-15

237

Dynamic Changes of Lipopolysaccharide Levels in Different Phases of Acute on Chronic Hepatitis B Liver Failure  

PubMed Central

Background High serum levels of lipopolysaccharide (LPS) with LPS-MD-2/TLR4 complex activated NF-kb and cytokine cause hepatic necrosis in animal models. We investigated the dynamic changes of LPS levels in patients with acute on chronic hepatitis B liver failure (ACHBLF). Methods We enrolled ACHBLF patients for a 12-week study. Patients’ LPS levels were measured along with 10 healthy controls. Patients on supportive care and recovered without intervention(s) were analyzed. Patients’ LPS levels during the disease progression phase, peak phase, and remission phase were compared with healthy controls. Results Among 30 patients enrolled, 25 who received interventions or expired during the study period were excluded from the analysis, five patients on supportive care who completed the study were analyzed. Significant abnormal distributions of LPS levels were observed in patients in different phases (0.0168±0.0101 in progression phase; 0.0960±0.0680 in peak phase; 0.0249±0.0365 in remission phase; and 0.0201±0.0146 in controls; respectively, p<0.05). The highest level of LPS was in the peak phase and significantly elevated when compared to controls (0.0201±0.0146 vs. 0.0960±0.0680, p?=?0.007). There were no statistically significant differences in LPS levels between healthy controls and subjects in the progression phase or remission phase. Dynamic changes of LPS were correlated with MELD-Na in the progression phase (p?=?0.01, R?=?0.876) and in the peak phase (p?=?0.000, R?=??1.00). Conclusions Significant abnormal distributions of LPS levels were observed in ACHBLF with the highest level in the peak phase. The dynamic changes of LPS were correlated with disease severity and suggested LPS causing secondary hepatic injury. PMID:23185336

Zhang, Wei; Zheng, Yubao; Peng, Liang; Deng, Hong; Chen, Youming; Chen, Lubiao; Chen, Sui; Zhang, Min; Gao, Zhiliang

2012-01-01

238

A randomised controlled trial of extended brief intervention for alcohol dependent patients in an acute hospital setting (ADPAC)  

PubMed Central

Background Alcohol dependence affects approximately 3% of the English population, and accounts for significant medical and psychiatric morbidity. Only 5.6% of alcohol-dependent individuals ever access specialist treatment and only a small percentage ever seek treatment. As people who are alcohol dependent are more likely to have experienced health problems leading to frequent attendance at acute hospitals it would seem both sensible and practical to ensure that this setting is utilised as a major access point for treatment, and to test the effectiveness of these treatments. Methods/Design This is a randomised controlled trial with a primary hypothesis that extended brief interventions (EBI) delivered to alcohol-dependent patients in a hospital setting by an Alcohol Specialist Nurse (ASN) will be effective when compared to usual care in reducing overall alcohol consumption and improving on the standard measures of alcohol dependence. Consecutive patients will be screened for alcohol misuse in the Emergency Department (ED) of a district general hospital. On identification of an alcohol-related problem, following informed written consent, we aim to randomize 130 patients per group. The ASN will discharge to usual clinical care all control group patients, and plan a programme of EBI for treatment group patients. Follow-up interview will be undertaken by a researcher blinded to the intervention at 12 and 24 weeks. The primary outcome measure is level of alcohol dependence as determined by the Severity of Alcohol Dependence Questionnaire (SADQ) score. Secondary outcome measures include; Alcohol Use Disorders Identification Test (AUDIT) score, quantity and frequency of alcohol consumption, health-related quality of life measures, service utilisation, and patient experience. The trial will also allow an assessment of the cost-effectiveness of EBI in an acute hospital setting. In addition, patient experience will be assessed using qualitative methods. Discussion This paper presents a protocol for a RCT of EBI delivered to alcohol dependent patients by an ASN within an ED. Importantly; the trial will also seek to understand patients' perceptions and experiences of being part of a RCT and of receiving this form of intervention. Trial registration number ISRCTN: ISRCTN78062794 PMID:21726445

2011-01-01

239

Regulation of TREM expression in hepatic macrophages and endothelial cells during acute endotoxemia.  

PubMed

Triggering receptor expressed on myeloid cells (TREM) regulates inflammatory responses to lipopolysaccharide (LPS). In these studies, we analyzed the expression of TREM in hepatic macrophages and endothelial cells which play a central role in LPS clearance. LPS administration to C3H/HeOuJ mice resulted in a rapid induction of TREM-1 and TREM-3, but a decrease in TREM-2 in liver macrophages and endothelial cells. The observation that TREM family members are detectable in endothelial cells is novel and demonstrates that their expression is not limited to myeloid cells. LPS-induced alterations in TREM expression were not evident in cells from C3H/HeJ TLR-4 mutant mice, indicating that the response is dependent on TLR-4. IL-1beta and TNFalpha upregulated TREM-1 and TREM-3 expression and suppressed TREM-2 expression in macrophages and endothelial cells. This activity involved PI3-kinase and p38 MAP kinase signaling. Interestingly, no significant differences were noted in TREM expression between wild-type and TNFR1-/- mice treated with LPS. Treatment of macrophages and endothelial cells with LPS upregulated expression of nitric oxide synthase-2 (NOS-2). This was blocked by TREM-1 Fc/fusion protein, indicating that TREM-1 mediates LPS-induced NOS-2 expression. These results suggest that TREM proteins are important in the inflammatory response of hepatic macrophages and endothelial cells to acute endotoxemia. PMID:18222421

Chen, Li C; Laskin, Jeffrey D; Gordon, Marion K; Laskin, Debra L

2008-04-01

240

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

PubMed Central

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

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

2009-01-01

241

Hepatic iron stores and markers of iron overload in alcoholics and patients with idiopathic hemochromatosis  

Microsoft Academic Search

Liver iron concentrations were determined in 60 alcoholics with liver disease of varying severity, 15 patients with untreated idiopathic hemochromatosis, and 16 control subjects with biliary tract disease. Mean liver iron concentrations (µg\\/100 mg dry weight) were significantly greater in the alcoholics (156.4±7.8 (sem);PP140 µg\\/100 mg were found in 17 alcoholics (29%) and in all 15 patients with idiopathic hemochromatosis.

R. W. Chapman; M. Y. Morgan; M. Laulicht; A. V. Hoffbrand; Sheila Sherlock

1982-01-01

242

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

SciTech Connect

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.

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

243

Protective role of antioxidants on thioacetamide-induced acute hepatic encephalopathy: biochemical and ultrastructural study.  

PubMed

Thioacetamide (TAA) has been used in development of animal models of acute hepatic encephalopathy (AHE). This experimental study was designed to evaluate effects of oral administration of vitamin C, vitamin E and their combination on liver and brain enzymes and their histologic and ultrastructure changes. Eighty Wistar rats were included and divided into five groups (16 each). Group 1 (control) received saline once intraperitoneally (IP) then administered orally saline and corn oil for 3 days. Group 2 [hepatotoxic (TAA)] were received TAA (300mg/kg) once intraperitoneally (IP). Group 3 (vitamin C and TAA) received TAA (300mg/kg) once intraperitoneally (IP) and then administered orally vitamin C (100mg/kg) daily for 3 days. Group 4 (vitamin E and TAA) received TAA (300mg/kg) once intraperitoneally (IP) and then administered orally vitamin E (200mg/kg) daily for 3 days. Group 5 (vitamin C and vitamin E and TAA) received TAA (300mg/kg) once intraperitoneally (IP) and then administered orally vitamin C (100mg/kg) in combination with vitamin E (200mg/kg) daily for 3 days. All rats were sacrificed 24h after last treatment under anesthesia. Blood samples were collected and serum was obtained for analysis of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), total protein, triglyceride, cholesterol using spectrophotometer and ELISA kits. Liver and brain were extracted and tissue homogenate was used to measure malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO). Histological and ultrastructure examination were done. TAA induced significant increase of MDA and decreased in GSH and NO in both liver and brain homogenate with more liver affection, and increased in serum levels of AST, ALT, triglyceride, cholesterol and decreased in total protein. Furthermore, there is decrease in serum levels of AST, ALT, triglyceride, cholesterol and tissue levels of MDA and elevated serum total protein and tissue GSH and NO under the umbrella of vitamin C and vitamin E and their combination, although vitamin E is more efficient. These data showed protective effect of vitamins C and E, especially vitamin E against oxidative stress and hepatic and brain damage, and histological architecture of the liver in rats' model of acute hepatic encephalopathy elicited by TAA. PMID:23876406

Mustafa, H N; El Awdan, Sally A; Hegazy, Gehan A

2013-10-01

244

Augmented central nitric oxide production inhibits vasopressin release during hemorrhage in acute alcohol-intoxicated rodents  

PubMed Central

Acute alcohol intoxication (AAI) attenuates the AVP response to hemorrhage, contributing to impaired hemodynamic counter-regulation. This can be restored by central cholinergic stimulation, implicating disrupted signaling regulating AVP release. AVP is released in response to hemorrhage and hyperosmolality. Studies have demonstrated nitric oxide (NO) to play an inhibitory role on AVP release. AAI has been shown to increase NO content in the paraventricular nucleus. We hypothesized that the attenuated AVP response to hemorrhage during AAI is the result of increased central NO inhibition. In addition, we predicted that the increased NO tone during AAI would impair the AVP response to hyperosmolality. Conscious male Sprague-Dawley rats (300–325 g) received a 15-h intragastric infusion of alcohol (2.5 g/kg + 300 mg·kg?1·h?1) or dextrose prior to a 60-min fixed-pressure hemorrhage (?40 mmHg) or 5% hypertonic saline infusion (0.05 ml·kg?1·min?1). AAI attenuated the AVP response to hemorrhage, which was associated with increased paraventricular NO content. In contrast, AAI did not impair the AVP response to hyperosmolality. This was accompanied by decreased paraventricular NO content. To confirm the role of NO in the alcohol-induced inhibition of AVP release during hemorrhage, the nitric oxide synthase inhibitor, nitro-l-arginine methyl ester (l-NAME; 250 ?g/5 ?l), was administered centrally prior to hemorrhage. l-NAME did not further increase AVP levels during hemorrhage in dextrose-treated animals; however, it restored the AVP response during AAI. These results indicate that AAI impairs the AVP response to hemorrhage, while not affecting the response to hyperosmolality. Furthermore, these data demonstrate that the attenuated AVP response to hemorrhage is the result of augmented central NO inhibition. PMID:21849630

Whitaker, Annie M.; Sulzer, Jesse K.

2011-01-01

245

Dopamine and Serotonin Transporter Availability During Acute Alcohol Withdrawal: Effects of Comorbid Tobacco Smoking  

Microsoft Academic Search

Tobacco smoking is highly comorbid with heavy alcohol drinking, yet the interaction of tobacco smoking and alcohol drinking on brain catecholaminergic synaptic markers is unexplored. Here we evaluate the effects of alcohol drinking alone from comorbid alcohol drinking and tobacco smoking on dopamine (DA) and serotonin (5-HT) transporter availability. A total of 14 heavy alcohol drinking smokers (n=6) and nonsmokers

Kelly P Cosgrove; Erica Krantzler; Erin B Frohlich; Stephanie Stiklus; Brian Pittman; Gilles D Tamagnan; Ronald M Baldwin; Frederic Bois; John P Seibyl; John H Krystal; Stephanie S O'Malley; Julie K Staley

2009-01-01

246

Hepatitis  

MedlinePLUS

... partner. Increased rates of hepatitis A infection among gay and bisexual men have been reported in many ... by many physicians with a large number of gay and bisexual male patients. As with all STDs, ...

247

Acute alcohol exposure, acidemia or glutamine administration impacts amino acid homeostasis in ovine maternal and fetal plasma  

PubMed Central

Fetal alcohol syndrome (FAS) is a significant problem in human reproductive medicine. Maternal alcohol administration alters maternal amino acid homeostasis and results in acidemia in both mother and fetus, causing fetal growth restriction. We hypothesized that administration of glutamine, which increases renal ammoniagenesis to regulate acid-base balance, may provide an intervention strategy. This hypothesis was tested using sheep as an animal model. On day 115 of gestation, ewes were anesthetized and aseptic surgery was performed to insert catheters into the fetal abdominal aorta as well as the maternal abdominal aorta and vena cava. On day 128 of gestation, ewes received intravenous administration of saline, alcohol [1.75 g/kg body weight (BW)/h], a bolus of 30 mg glutamine/kg BW, alcohol + a bolus of 30 mg glutamine/kg BW, a bolus of 100 mg glutamine/kg BW, alcohol + a bolus of 100 mg glutamine/kg BW, or received CO2 administration to induce acidemia independent of alcohol. Blood samples were obtained simultaneously from the mother and the fetus at times 0 and 60 min (the time of peak blood alcohol concentration) of the study. Administration of alcohol to pregnant ewes led to a reduction in concentrations of glutamine and related amino acids in plasma by 21–30%. An acute administration of glutamine to ewes, concurrent with alcohol administration, improved the profile of most amino acids (including citrulline and arginine) in maternal and fetal plasma. We suggest that glutamine may have a protective effect against alcohol-induced metabolic disorders and FAS in the ovine model. PMID:23315157

Washburn, Shannon E.; Sawant, Onkar B.; Lunde, Emilie R.; Wu, Guoyao; Cudd, Timothy A.

2013-01-01

248

Serological misdiagnosis of acute liver failure associated with echovirus 25 due to immunological similarities to hepatitis a virus and prozone effect.  

PubMed

We describe a case of acute liver failure caused by echovirus 25 (E25) in a previously healthy 2-year-old boy. Initial serological studies were consistent with hepatitis A virus (HAV), with prozone phenomenon. The similarity of E25 to HAV may obscure accurate diagnosis in some cases of hepatitis. PMID:25355762

Wollersheim, Susan K; Humphries, Romney M; Cherry, James D; Krogstad, Paul

2015-01-01

249

Fenugreek (Trigonella foenum graecum) seed polyphenols protect liver from alcohol toxicity: a role on hepatic detoxification system and apoptosis.  

PubMed

The present study investigates the hepatoprotective effect of fenugreek seed polyphenolic extract (FPEt) against ethanol-induced hepatic injury and apoptosis in rats. Chronic ethanol administration (6 g/kg/day x 60 days) caused liver damage that was manifested by the elevation of markers of liver dysfunction--aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), bilirubin and gamma-glutamyl transferase (GGT) in plasma and reduction in liver glycogen. The effects on alcohol metabolizing enzymes such as alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) were studied and found to be altered in the alcohol-treated group. Ethanol administration resulted in adaptive induction of the activities of cytochrome p450 (cyt-p-450) and cytochrome-b5 (cyt-b5) and reduction in cytochrome-c-reductase (cyt-c-red) and glutathione-S-tranferase (GST), a phase II enzyme. Further, ethanol reduced the viability of isolated hepatocytes (ex vivo) as assessed by the trypan blue exclusion test and increased hepatocyte apoptosis as assessed by propidium iodide staining (PI). Treatment with FPEt restored the levels of markers of liver injury and mitigated the alterations in alcohol metabolizing and detoxification enzymes and the electron transport component cytochrome-c reductase. Increased hepatocyte viability and reduced apoptotic nuclei were observed in FPEt-treated rats. These findings demonstrate that FPEt acts as a protective agent against ethanol-induced abnormalities in the liver. The effects of FPEt are comparable with those of a known hepatoprotective agent, silymarin. PMID:17484288

Kaviarasan, S; Anuradha, C V

2007-04-01

250

Alcohol  

Microsoft Academic Search

\\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

William E. M. Lands

251

The Role Of Alcohol in Severe Pneumonia and Acute Lung Injury  

Microsoft Academic Search

\\u000a Alcohol is the most frequently abused drug in the world (1). In the United States, approximately 50% of the adult population regularly consume alcohol, and 15 to 20 million individuals\\u000a are alcoholic’s (1). The effects of alcohol abuse on our health care system are concerning. Alcohol is the third leading cause of preventable\\u000a mortality and is associated with an estimated

Marc Moss

252

Symptomatic Acute Hepatitis C in Egypt: Diagnosis, Spontaneous Viral Clearance, and Delayed Treatment with 12 Weeks of Pegylated Interferon Alfa-2a  

PubMed Central

Background and Objectives The aim of this study was to estimate the proportion of spontaneous viral clearance (SVC) after symptomatic acute hepatitis C and to evaluate the efficacy of 12 weeks of pegylated interferon alfa-2a in patients who did not clear the virus spontaneously. Methods Patients with symptomatic acute hepatitis C were recruited from two “fever hospitals” in Cairo, Egypt. Patients still viremic three months after the onset of symptoms were considered for treatment with 12 weeks of pegylated interferon alfa-2a (180 µg/week). Results Between May 2002 and February 2006, 2243 adult patients with acute hepatitis were enrolled in the study. The SVC rate among 117 patients with acute hepatitis C was 33.8% (95%CI [25.9%–43.2%]) at three months and 41.5% (95%CI [33.0%–51.2%]) at six months. The sustained virological response (SVR) rate among the 17 patients who started treatment 4–6 months after onset of symptoms was 15/17?=?88.2% (95%CI [63.6%–98.5%]). Conclusion Spontaneous viral clearance was high (41.5% six months after the onset of symptoms) in this population with symptomatic acute hepatitis C. Allowing time for spontaneous clearance should be considered before treatment is initiated for symptomatic acute hepatitis C. PMID:19115010

Sharaf Eldin, Noha; Ismail, Soheir; Mansour, Hala; Rekacewicz, Claire; El-Houssinie, Moustafa; El-Kafrawy, Sherif; El Aidi, Saeed; Abdel-Hamid, Mohamed; Esmat, Gamal; Pol, Stanislas; Fontanet, Arnaud; Mohamed, Mostafa K.

2008-01-01

253

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

PubMed

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

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

2014-08-01

254

Refractory status epilepticus due to acute hepatic porphyria in a pregnant woman: induced abortion as the sole therapeutic option?  

PubMed

A 22-years old, 55 kg female patient in the twelfth week of pregnancy developed neuropsychiatric syndromes and in the following status epilepticus. Raised porphyrines and porphyrine precursors were found in the patient's urine. Despite intravenous glucose infusions and appropriate medication no reduction in seizure-frequency and neuropsychiatric syndromes was observed. An abortion was induced. After the interruption and starting of haem arginate therapy, seizure activity stopped and porphyrine precursors returned to normal levels, and after 6 weeks the patient was discharged in excellent clinical condition. This report describes a status epilepticus caused by acute hepatic porphyria, triggered by pregnancy, in a 22-years old woman. To our knowledge this is the first report of induced abortion as successful treatment in acute hepatic porphyria induced status epilepticus. PMID:15469454

Engelhardt, K; Trinka, E; Franz, G; Unterberger, I; Spiegel, M; Beer, R; Pfausler, B; Kampfl, A; Schmutzhard, E

2004-10-01

255

Nonselective inhibition of prostaglandin-endoperoxide synthase by naproxen ameliorates hepatic injury in animals with acute or chronic liver injury  

PubMed Central

The rising prevalence of hepatic injury due to toxins, metabolites, viruses, etc., necessitates development of further mechanisms for protecting the liver and for treating acute or chronic liver diseases. To examine whether inhibition of inflammation directed by cyclo-oxygenase pathways, we performed animal studies with naproxen, which inhibits prostaglandin-endoperoxide synthases 1 and 2 and is in extensive clinical use. We administered carbon tetrachloride to induce acute liver injury and ligated the common bile duct to induce chronic liver injury in adult rats. These experimental manipulations produced abnormalities in liver tests, tissue necrosis, compensatory hepatocyte or biliary proliferation, and onset of fibrosis, particularly after bile duct ligation. After carbon tetrachloride-induced acute injury, naproxen decreased liver test abnormalities, tissue necrosis and compensatory hepatocellular proliferation. After bile duct ligation-induced chronic injury, naproxen decreased liver test abnormalities, tissue injury and compensatory biliary hyperplasia. Moreover, after bile duct ligation, naproxen-treated rats showed more periductular oval liver cells, which have been classified as hepatic progenitor cells. In naproxen-treated rats, we found greater expression in hepatic stellate cells and mononuclear cells of cytoprotective factors, such as vascular endothelial growth factor. The ability of naproxen to induce expression of vascular endothelial growth factor was verified in cell culture studies with CFSC-8B clone of rat hepatic stellate cells. Whereas assays for carbon tetrachloride toxicity using cultured primary hepatocytes established that naproxen was not directly cytoprotective, we found conditioned medium containing vascular endothelial growth factor from naproxen-treated CFSC-8B cells protected hepatocytes from carbon tetrachloride toxicity. Therefore, naproxen was capable of ameliorating toxic liver injury, which involved naproxen-induced release of physiological cytoprotective factors in nonparenchymal liver cells. Such drug-induced release of endogenous cytoprotectants will advance therapeutic development for hepatic injury. PMID:24220607

Bahde, Ralf; Kapoor, Sorabh; Gupta, Sanjeev

2014-01-01

256

Primary follicular lymphoma of the spleen incidentally found in a patient with alcohol- and hepatitis C-related liver cirrhosis  

PubMed Central

Primary splenic lymphoma is rare as non-Hodgkin lymphomas. Splenic infiltration of lymphoma cells may cause splenomegaly in many cases. However, splenomegaly is caused not only by tumor involvement but also by non-tumorous disorders. One of the most prevalent non-neoplastic causes is portal hypertension mostly due to liver cirrhosis. On the other hand, liver cirrhosis may underlie various extrahepatic manifestations including development of B-cell non-Hodgkin lymphomas. Here, we report a case of primary follicular lymphoma of the spleen in a patient with liver cirrhosis related to hepatitis C and alcohol. The lymphoma was incidentally found in an enlarged spleen resected palliatively to alleviate symptomatic pancytopenia of the patient. The main characteristic of our case is an incidental finding of a rare situation brought by careful pathological examination. Our case illustrates the importance to recognize a possibility of co-occurrence of chronic liver disease and extrahepatic lymphoma. PMID:25120838

Matsuda, Ikuo; Okada, Masaya; Inoue, Takayuki; Tokugawa, Tazuko; Ogawa, Hiroyasu; Hirota, Seiichi

2014-01-01

257

Ferritin L is the sole serum ferritin constituent and a positive hepatic acute-phase protein.  

PubMed

Ferritin L (FTL) and ferritin H (FTH) subunits are responsible for intracellular iron storage. Serum ferritin levels are not only dependant on body iron stores. Aims of the present study are to demonstrate nature, source, and major regulatory mediators of serum ferritin in an animal model of acute-phase (AP) response. Animals (rats, wild-type [WT] mice, and interleukin [IL]-6ko mice) were injected with turpentine oil (TO) intra-muscularity to induce a sterile abscess and sacrificed at different time points afterward. Rat hepatocytes were isolated for cell culture and, after reaching confluence, stimulated with major AP cytokines to induce AP conditions. We found a significantly increased expression of both ferritin subunits in liver at mRNA and protein levels during AP response. In the serum of both control and TO-injected rats, only FTL was detectable by Western blotting, whereas no increase in serum FTL was measured by Western blot or enzyme-linked immunosorbent assay. An increase in protein expression of FTL and FTH was observed in lysates of rat hepatocytes after treatment with IL-6, IL-1?, and tumor necrosis factor-?; however, only FTL was increasingly released into supernatant. In both TO-injected rats and WT mice, a dramatic increase in serum IL-6 levels was observed, along with an increased amount of hepatic ferritin subunits. However, an increase of hepatic FTL but not of FTH protein expression was observed in IL-6ko mice after TO injection. Our data demonstrate that FTL is the only rat serum ferritin whose release into circulation from the hepatocytes is increased by the effect of AP cytokines (e.g., IL-6). In contrast, FTH expression is intracellular in both under physiological and AP conditions. PMID:23524846

Naz, Naila; Moriconi, Federico; Ahmad, Shakil; Amanzada, Ahmad; Khan, Sajjad; Mihm, Sabine; Ramadori, Guiliano; Malik, Ihtzaz Ahmed

2013-06-01

258

Predictors of spontaneous viral clearance and outcomes of acute hepatitis C infection  

PubMed Central

Background/Aims This study evaluated the predictors of spontaneous viral clearance (SVC), as defined by two consecutive undetectable hepatitis C virus (HCV) RNA tests performed ?12 weeks apart, and the outcomes of acute hepatitis C (AHC) demonstrating SVC or treatment-induced viral clearance. Methods Thirty-two patients with AHC were followed for 12-16 weeks without administering antiviral therapy. Results HCV RNA was undetectable at least once in 14 of the 32 patients. SVC occurred in 12 patients (37.5%), among whom relapse occurred in 4. SVC was exhibited in 8 of the 11 patients exhibiting undetectable HCV RNA within 12 weeks. HCV RNA reappeared in three patients (including two patients with SVC) exhibiting undetectable HCV RNA after 12 weeks. SVC was more frequent in patients with low viremia than in those with high viremia (55.6% vs. 14.3%; P=0.02), and in patients with HCV genotype non-1b than in those with HCV genotype 1b (57.1% vs. 22.2%; P=0.04). SVC was more common in patients with a ?2 log reduction of HCV RNA at 4 weeks than in those with a smaller reduction (90% vs. 9.1%, P<0.001). A sustained viral response was achieved in all patients (n=18) receiving antiviral therapy. Conclusions Baseline levels of HCV RNA and genotype non-1b were independent predictors for SVC. A ?2 log reduction of HCV RNA at 4 weeks was a follow-up predictor for SVC. Undetectable HCV RNA occurring after 12 weeks was not sustained. All patients receiving antiviral therapy achieved a sustained viral response. Antiviral therapy should be initiated in patients with detectable HCV RNA at 12 weeks after the diagnosis.

Cho, Yoo-Kyung; Kim, Young Nam

2014-01-01

259

Brief motivational intervention for adolescents treated in emergency departments for acute alcohol intoxication – a randomized-controlled trial  

PubMed Central

Background Alcohol misuse among youth is a major public health concern and numbers of adolescents admitted to the emergency department for acute alcoholic intoxication in Germany are recently growing. The emergency setting offers an opportunity to reach at-risk alcohol consuming adolescents and provide brief interventions in a potential “teachable moment”. However, studies on brief interventions targeting adolescents in emergency care are scarce and little is known about their effectiveness when delivered immediately following hospitalization for acute alcohol intoxication. In this protocol we present the HaLT-Hamburg trial evaluating a brief motivational intervention for adolescents treated in the emergency department after an episode of acute alcoholic intoxication. Methods The trial design is a parallel two-arm cluster randomized-controlled trial with follow-up assessment after 3 and 6 months. N?=?312 participants aged 17 years and younger will be recruited Fridays to Sundays in 6 pediatric clinics over a period of 30 months. Intervention condition is a manual-based brief motivational intervention with a telephone booster after 6 weeks and a manual-guided intervention for caregivers which will be compared to treatment as usual. Primary outcomes are reduction in binge drinking episodes, quantity of alcohol use on a typical drinking day and alcohol-related problems. Secondary outcome is further treatment seeking. Linear mixed models adjusted for baseline differences will be conducted according to intention-to-treat (ITT) and completers (per-protocol) principles to examine intervention effects. We also examine quantitative and qualitative process data on feasibility, intervention delivery, implementation and receipt from intervention providers, receivers and regular emergency department staff. Discussion The study has a number of strengths. First, a rigorous evaluation of HaLT-Hamburg is timely because variations of the HaLT project are widely used in Germany. Second, prior research has not targeted adolescents in the presumed teachable moment following acute alcohol intoxication. Third, we included a comprehensive process evaluation to raise external validity. Fourth, the study involved important stakeholders from the start to set up organizational structures for implementation and maintaining project impact. Trial registration Current Controlled Trials ISRCTN31234060 (April 30th 2012). PMID:24975110

2014-01-01

260

In vitro inactivation of hepatic alcohol dehydrogenase and aldehyde dehydrogenases from rats by dithiocarbamates with or without metals  

SciTech Connect

Alcohol dehydrogenases is localized mainly in the hepatic cytoplasm. Aldehyde dehydrogenases are bound predominantly to the hepatic mitochondrial and endoplasmic reticular membranes; a small part of their total activity is measured in the cytosol. ALDH catalyses the oxidation of acetaldehyde to acetic acid and the metabolism of endogenous or exogenous aldehydes. The goal of the present investigation was to examine in vitro the possible interaction of metal containing dithiocarbamates with the activity of ALDH isolated from rat livers in comparison with that of dithiocarbamates without metals. In addition, the elucidation of an inhibitory effect on isolated liver ADH possibly caused by dithiocarbamates with or without metals could help to explain a previously found delay of ethanol elimination from rat blood. To this end the following substances were tested: The dimers TMTD and TETD, the monomers dimethyldithiocarbamate (DMDC) as sodium salt or as zinc salt and diethyldithiocarbamate (DEDC) as sodium salt, as well as the related compounds tetramethylthiuram monosulfide (TMTM), manganese(II)-(N,N'-ethylenebis(dithiocarbamate)), and zinc-(N,N'-ethylenebis(dithiocarbamate)).

Freundt, K.J.; Schreiner, E.

1988-10-01

261

IgM and IgA antibodies generated against hepatitis C virus core antigen in patients with acute and chronic HCV infection  

Microsoft Academic Search

Antibody subclasses directed against the core protein (HCc) of hepatitis C virus (HCV) were measured in 27 patients with acute non-A, non-B (NANB) hepatitis, and 99 patients with chronic HCV-associated liver disease. IgM, IgA, and IgG anti-HCc responses were observed in 11 (40.7%), 7 (25.9%), and 18 (67%) patients with acute NANB hepatitis, respectively. Twenty-four (24.2%) and 40 (40.4%) patients

Shinjiro Sato; Shigetoshi Fujiyama; Motohiko Tanaka; Masafumi Goto; Yuko Taura; Shin-Ichi Kawano; Tatsuo Sato; Hiroyuki Yasuo

1994-01-01

262

Liver transplantation for acute intermittent porphyria is complicated by a high rate of hepatic artery thrombosis.  

PubMed

Acute intermittent porphyria (AIP) is an autosomal-dominant condition resulting from a partial deficiency of the ubiquitously expressed enzyme porphobilinogen deaminase. Although its clinical expression is highly variable, a minority of patients suffer recurrent life-threatening neurovisceral attacks despite optimal medical therapy. Because the liver is the major source of excess precursor production, liver transplantation (LT) represents a potentially effective treatment for severely affected patients. Using data from the U.K. Transplant Registry, we analyzed all transplants performed for AIP in the United Kingdom and Ireland. Between 2002 and 2010, 10 patients underwent LT for AIP. In all cases, the indication for transplantation was recurrent, biochemically proven, medically nonresponsive acute attacks of porphyria resulting in significantly impaired quality of life. Five patients had developed significant neurological morbidities such as paraplegia before transplantation. The median follow-up time was 23.4 months, and there were 2 deaths from multiorgan failure at 98 days and 26 months. Eight recipients were alive for 3.2 to 109 months after transplantation. Complete biochemical and symptomatic resolution was observed in all patients after transplantation. However, there was a high rate of hepatic artery thrombosis (HAT; 4/10), with 1 patient requiring regrafting. The effects of previous neuronal damage such as joint contractures were not improved by transplantation. Thus, impaired quality of life in the surviving patients was usually a result of preoperative complications. Refractory AIP is an excellent indication for LT, and long-term outcomes for carefully selected patients are good. There is, however, an increased incidence of HAT in these patients, and we recommend routine antiplatelet therapy after transplantation. PMID:21618697

Dowman, Joanna K; Gunson, Bridget K; Mirza, Darius F; Bramhall, Simon R; Badminton, Mike N; Newsome, Philip N

2012-02-01

263

Liver Transplantation for Acute Intermittent Porphyria is Complicated by a High Rate of Hepatic Artery Thrombosis  

PubMed Central

Acute intermittent porphyria (AIP) is an autosomal-dominant condition resulting from a partial deficiency of the ubiquitously expressed enzyme porphobilinogen deaminase. Although its clinical expression is highly variable, a minority of patients suffer recurrent life-threatening neurovisceral attacks despite optimal medical therapy. Because the liver is the major source of excess precursor production, liver transplantation (LT) represents a potentially effective treatment for severely affected patients. Using data from the UK Transplant Registry, we analyzed all transplants performed for AIP in the United Kingdom and Ireland. Between 2002 and 2010, 10 patients underwent LT for AIP. In all cases, the indication for transplantation was recurrent, biochemically proven, medically nonresponsive acute attacks of porphyria resulting in significantly impaired quality of life. Five patients had developed significant neurological morbidities such as paraplegia before transplantation. The median follow-up time was 23.4 months, and there were 2 deaths from multiorgan failure at 98 days and 26 months. Eight recipients were alive for 3.2 to 109 months after transplantation. Complete biochemical and symptomatic resolution was observed in all patients after transplantation. However, there was a high rate of hepatic artery thrombosis (HAT; 4/10), with 1 patient requiring regrafting. The effects of previous neuronal damage such as joint contractures were not improved by transplantation. Thus, impaired quality of life in the surviving patients was usually a result of preoperative complications. Refractory AIP is an excellent indication for LT, and long-term outcomes for carefully selected patients are good. There is, however, an increased incidence of HAT in these patients, and we recommend routine antiplatelet therapy after transplantation. Liver Transpl 18:195–200, 2012. © 2011 AASLD. PMID:21618697

Dowman, Joanna K; Gunson, Bridget K; Mirza, Darius F; Bramhall, Simon R; Badminton, Mike N; Newsome, Philip N

2012-01-01

264

Prospective Follow-Up of Patients with Acute Hepatitis C Virus Infection in Brazil  

PubMed Central

Background The natural outcome of infection with hepatitis C virus (HCV) varies substantially among individuals. However, little is known about host and viral factors associated with a self-limiting or chronic evolution of HCV infection. Methods From 1 January 2001 through 31 December 2008, a consecutive series of 65 patients from Rio de Janeiro, Brazil, with a well-documented diagnosis of acute HCV infection, acquired via various routes, were enrolled in this study. Patients were prospectively followed up for a median of 40 months after the estimated date of HCV infection with serial measurements of serum alanine aminotransferase, HCV RNA, and anti-HCV antibodies. Spontaneous viral clearance (SVC) was defined as undetectable levels of HCV RNA in serum, in the absence of treatment, for 3 consecutive HCV polymerase chain reaction tests within the first 6 months of follow-up. Cox proportional hazards regression was used to identify host and viral predictors of SVC. Results The cumulative rate of SVC was 44.6% (95% confidence interval, 32.3%–57.5%). Compared with chronic HCV evolution, patients with self-limiting disease had significantly lower peak levels of anti-HCV antibodies (median, 109.0 vs 86.7 optical density–to–cutoff ratio [od/co]; P < .02), experienced disease symptoms more frequently (69.4% vs 100%; P < .001), and had lower viral load at first clinical presentation (median, 4.3 vs 0.0 log copies; P =.01). In multivariate analyses, low peak anti-HCV level (<93.5 od/co) was the only independent predictor for SVC; the hazard ratio compared with high anti-HCV levels (?93.5 od/co) was 2.62 (95% confidence interval, 1.11–6.19; P =.03). Conclusion Our data suggest that low levels of anti-HCV antibodies during the acute phase of HCV infection are independently related to spontaneous viral clearance. PMID:20235831

Lewis-Ximenez, Lia L.; Lauer, Georg M.; zur Wiesch, Julian Schulze; de Sousa, Paulo Sergio Fonseca; Ginuino, Cleber F.; Paranhos-Baccalá, Gláucia; Ulmer, Hanno; Pfeiffer, Karl P.; Goebel, Georg; Pereira, João Luiz; de Oliveira, Jaqueline Mendes; Yoshida, Clara Fumiko Tachibana; Lampe, Elisabeth; Velloso, Carlos Eduardo; Pinto, Marcelo Alves; Coelho, Henrique Sergio; Almeida, Adilson José; Fernandes, Carlos Augusto; Kim, Arthur Y.; Strasak, Alexander M.

2013-01-01

265

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

PubMed Central

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

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

266

Acute Alcohol Intoxication Prolongs Neuroinflammation without Exacerbating Neurobehavioral Dysfunction following Mild Traumatic Brain Injury  

PubMed Central

Abstract Traumatic brain injury (TBI) represents a leading cause of death and disability among young persons with ?1.7 million reported cases in the United States annually. Although acute alcohol intoxication (AAI) is frequently present at the time of TBI, conflicting animal and clinical reports have failed to establish whether AAI significantly impacts short-term outcomes after TBI. The objective of this study was to determine whether AAI at the time of TBI aggravates neurobehavioral outcomes and neuroinflammatory sequelae post-TBI. Adult male Sprague-Dawley rats were surgically instrumented with gastric and vascular catheters before a left lateral craniotomy. After recovery, rats received either a primed constant intragastric alcohol infusion (2.5?g/kg+0.3?g/kg/h for 15?h) or isocaloric/isovolumic dextrose infusion followed by a lateral fluid percussion TBI (?1.4?J, ?30?ms). TBI induced apnea and a delay in righting reflex. AAI at the time of injury increased the TBI induced delay in righting reflex without altering apnea duration. Neurological and behavioral dysfunction was observed at 6?h and 24?h post-TBI, and this was not exacerbated by AAI. TBI induced a transient upregulation of cortical interleukin (IL)-6 and monocyte chemotactic protein (MCP)-1 mRNA expression at 6?h, which was resolved at 24?h. AAI did not modulate the inflammatory response at 6?h but prevented resolution of inflammation (IL-1, IL-6, tumor necrosis factor-?, and MCP-1 expression) at 24?h post-TBI. AAI at the time of TBI did not delay the recovery of neurological and neurobehavioral function but prevented the resolution of neuroinflammation post-TBI. PMID:24050411

Teng, Sophie X.

2014-01-01

267

Effect of intestinal microbiota alteration on hepatic damage in rats with acute rejection after liver transplantation.  

PubMed

The previous studies all focus on the effect of probiotics and antibiotics on infection after liver transplantation. Here, we focus on the effect of gut microbiota alteration caused by probiotics and antibiotics on hepatic damage after allograft liver transplantation. Brown-Norway rats received saline, probiotics, or antibiotics via daily gavage for 3 weeks. Orthotopic liver transplantation (OLT) was carried out after 1 week of gavage. Alteration of the intestinal microbiota, liver function and histopathology, serum and liver cytokines, and T cells in peripheral blood and Peyer's patch were evaluated. Distinct segregation of fecal bacterial diversity was observed in the probiotic group and antibiotic group when compared with the allograft group. As for diversity of intestinal mucosal microbiota and pathology of intestine at 2 weeks after OLT, antibiotics and probiotics had a significant effect on ileum and colon. The population of Lactobacillus and Bifidobacterium in the probiotic group was significantly greater than the antibiotic group and the allograft group. The liver injury was significantly reduced in the antibiotic group and the probiotic group compared with the allograft group. The CD4/CD8 and Treg cells in Peyer's patch were decreased in the antibiotic group. The intestinal Treg cell and serum and liver TGF-? were increased markedly while CD4/CD8 ratio was significantly decreased in the probiotic group. It suggested that probiotics mediate their beneficial effects through increase of Treg cells and TGF-? and deduction of CD4/CD8 in rats with acute rejection (AR) after OLT. PMID:25004996

Xie, Yirui; Chen, Huazhong; Zhu, Biao; Qin, Nan; Chen, Yunbo; Li, Zhengfeng; Deng, Min; Jiang, Haiyin; Xu, Xiangfei; Yang, Jiezuan; Ruan, Bing; Li, Lanjuan

2014-11-01

268

Biodistribution and acute toxicity of naked gold nanoparticles in a rabbit hepatic tumor model  

PubMed Central

There is a paucity of data regarding the safety of administering solid gold nanoparticles (AuNPs) in large animal tumor models. We assessed the acute toxicity and biodistribution of 5 nm and 25 nm solid AuNPs in New Zealand White rabbits (n = 6 in each) with implanted liver Vx2 tumors 24 hours after intravenous injection. Gold concentration was determined by inductively coupled plasma atomic emission spectrometry (ICP) and imaged with transmission electron microscopy (TEM). There was no clinico-pathologic evidence of renal, hepatic, pulmonary, or other organ dysfunction. After 25 nm AuNP administration, the concentration of white blood cells increased after treatment (p = 0.001). Most other blood studies were unchanged. AuNPs were distributed to the spleen, liver, and Vx2 tumors, but not to other tissues. The urinary excretion of AuNPs was bimodal as measured by ICP. 25 nm AuNPs were more evenly distributed throughout tissues and may be better tools for medical therapy. PMID:20854190

GLAZER, EVAN S; ZHU, CIHUI; HAMIR, AMIR N.; BORNE, AGATHA; THOMPSON, C. SHEA; CURLEY, STEVEN A.

2012-01-01

269

Effect of bone marrow mesenchymal stem cell transplantation on acute hepatic failure in rats.  

PubMed

The aim of the present study was to investigate the effectiveness of bone marrow mesenchymal stem cell (BMSC) transplantation in the treatment of acute hepatic failure (AHF) in rats. BMSCs were isolated from rat bone marrow, cultured and analyzed by flow cytometry. Following BMSC transplantation into rats with AHF, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), direct bilirubin (DBIL) and indirect bilirubin (IBIL) in the serum were measured using an automatic biochemical analyzer. Hematoxylin and eosin (H&E) staining and a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were performed to analyze the pathological changes and apoptosis rate. Levels of cluster of differentiation (CD)163 and interleukin (IL)-10 in the serum and liver tissue were detected by an enzyme-linked immunosorbent assay (ELISA) assay and western blot analysis. Compared with the levels in the control group, the serum levels of ALT, AST, DBIL, IBIL, CD163 and IL-10 in the BMSC transplantation groups were significantly lower at 120 and 168 h, while the serum levels of ALB were significantly higher at 168 h after BMSC transplantation. The pathological features of liver failure were alleviated by BMSC transplantation. The expression levels of CD163 and IL-10 in the liver tissue were also significantly decreased following transplantation. The results indicate that BMSCs have a therapeutic effect on AHF in rats, and CD163 and IL-10 may be used as sensitive serum prognosis indicators in the early assessment of patients following liver transplantation. PMID:25187814

Yuan, Shufang; Jiang, Tao; Zheng, Rongjiong; Sun, Lihua; Cao, Guiqiu; Zhang, Yuexin

2014-10-01

270

Induction of hepatic Bach1 mRNA expression by carbon tetrachloride-induced acute liver injury in rats  

PubMed Central

Hepatic oxidative stress is a major contributor to the pathogenesis of several acute liver diseases. Diagnostic markers of hepatic oxidative stress may facilitate early detection and intervention. Bach1 is an oxidative stress-responsive transcription factor that represses heme oxygenase 1 (HO-1), the rate-limiting enzyme in the catabolism of heme, a potent pro-oxidant. We previously demonstrated that carbon tetrachloride (CCl4) causes oxidative hepatic injury in rats, exacerbated by free heme, suggesting that CCl4 may affect Bach1 gene expression. In the present study, we used northern blot analysis to measure Bach1, HO-1 and ?-aminolevulinate synthase (ALAS1; a heme biosynthesis enzyme) mRNA expression levels during acute hepatic injury induced by CCl4 (at doses of 0.1, 1.0 and 2.0 ml/kg body weight). Oxidative injury was assessed by measuring serum alanine aminotransferase (ALT), hepatic malondialdehyde (MDA) and glutathione (GSH) content. Treatment with CCl4 induced a significant dose-dependent increase in Bach1 mRNA 1–3 h after administration. Bach1 mRNA peaked at 6 h after CCl4 treatment (1 ml/kg), followed by a rapid decrease and gradual return to baseline by 12 h after treatment. The timecourse of transient Bach1 mRNA induction roughly mirrored that of HO-1 mRNA, while ALAS1 mRNA was inversely downregulated. Serum ALT levels and hepatic MDA concentration were significantly increased at 24 h after CCl4 treatment, while the hepatic GSH content was significantly reduced within 3 h of treatment. Serum ALT levels were positively correlated with Bach1 mRNA levels. These findings indicate that Bach1 mRNA is transiently induced in rat liver by CCl4, possibly as a regulatory mechanism to restore HO-1 to baseline following free heme catabolism. Our findings also suggest that Bach1 mRNA expression may be a novel indicator of the extent of oxidative hepatic injury caused by free heme. PMID:24748974

TANIOKA, NOHITO; SHIMIZU, HIROKO; TAKAHASHI, TORU; OMORI, EMIKO; KURODA, KOSUKE; SHIBATA, MARI; YAMAOKA, MASAKAZU; TODA, YUICHIRO; MATSUSAKI, TAKASHI; MORIMATSU, HIROSHI

2014-01-01

271

Acute Pancreatitis Associated with Pegylated Interferon and Ribavirin Treatment of Chronic Hepatitis C, Genotype 1b with High Viral Load  

PubMed Central

Acute pancreatitis, an uncommon side effect of pegylated interferon ? (PEG-IFN ?) and ribavirin (RBV) combination therapy, has rarely been reported in the English language literature. Here, acute pancreatitis associated with PEG-IFN plus RBV treatment is described in three patients with chronic hepatitis C, genotype 1b with high serum hepatitis C virus RNA levels. The patients had been started on weekly subcutaneous injections of PEG-IFN ? (60, 80, and 90 ?g) plus a daily oral dose of RBV (600 mg). The therapy was discontinued, however, because of the onset of acute pancreatitis (after 15 weeks, 48 weeks, and 3 weeks respectively). The drug-induced pancreatitis was diagnosed on the basis of elevated levels of amylase and lipase and the absence of other identifiable causes. High tumor necrosis factor-? was found in one patient and high interleukin-6 in the other two. The immune system stimulated by PEG-IFN and RBV combination therapy might have caused the acute pancreatitis. Further study is needed to clarify the mechanism of the onset of drug-induced pancreatitis by PEG-IFN and RBV combination therapy. PMID:21103256

Ando, Kenji; Kim, Soo Ryang; Imoto, Susumu; Nakajima, Taisuke; Mita, Keiji; Fukuda, Katsumi; Taniguchi, Miyuki; Sasase, Noriko; Muramatsu, Akira; Matsuoka, Toshiyuki; Kudo, Masatoshi; Hayashi, Yoshitake

2009-01-01

272

Hepatitis B virus (HBV) core antigen-specific regulatory T cells confer sustained remission to anti-HBV therapy in chronic hepatitis B with acute exacerbation.  

PubMed

Acute exacerbations (AEs) of chronic hepatitis B (CH-B) are thought to be the result of breakdown of immune tolerance on the natural history of chronic hepatitis B virus (HBV) infection. Immune tolerance to HBV maintained in CH-B patients without hepatitis is under the control of the host's forkhead box p3-expressing regulatory T cells (Tregs). Its breakdown mimics the occurrence of autoimmune diseases. Severe AEs may lead to liver decompensation and mortalities. Consequently, AEs are currently the major therapeutic targets in patient treatment. In this study, we employed the SYFPEITHI scoring system to identify epitopes on HBV core antigen (HBcAg) for the construction of human leukocyte antigen class II tetramers to measure HBcAg-specific Treg frequencies (Tregf). Upregulation of Treg gene profiling accompanied by increased HBcAg-specific Tregf was detected in AE patients with sustained remission (SR) to anti-HBV therapy. Depletion of Tregs from peripheral blood mononuclear cells enhanced proliferation to HBcAg. HBcAg-specific Treg clones inhibited the killing capacity of cytotoxic T lymphocyte clones in an antigen-independent manner. A greater posttherapy increase in HBcAg-specific Tregf correlated with a higher SR rate to anti-HBV therapy. These results suggest that HBcAg-specific Tregs function as suppressor effectors and confer SR to anti-HBV therapy. PMID:21215784

Koay, Lok-Beng; Feng, I-Che; Sheu, Ming-Jen; Kuo, Hsing-Tao; Lin, Chin-Yih; Chen, Jyh-Jou; Wang, Shih-Ling; Tang, Ling-Yu; Tsai, Sun-Lung

2011-09-01

273

Chronic alcohol ingestion modulates hepatic macrophage populations and functions in mice.  

PubMed

Hepatic Macs, consisting of resident KCs and infiltrating monocytes/IMs, are thought to play an important role in the pathogenesis of ALD. Previous work has focused on KCs or studied hepatic Macs as one cell population. The aim of the current study is to distinguish IMs from KCs and to compare their phenotypes and functions. We show here that a 4-week ethanol feeding of C57BL/6J mice causes recruitment of IMs into the liver. KCs and IMs can be distinguished based on their differential expression of F4/80 and CD11b. IMs can be divided further into two subsets based on their differential expression of Ly6C. KCs and two subsets of IMs were separately purified by FACS. The phagocytosis abilities and the expression profiles of genes related to various functions were compared among different populations of hepatic Macs. Ly6C(low) IMs exhibit an anti-inflammatory and tissue-protective phenotype; in contrast, Ly6C(hi) IMs exhibit a proinflammatory, tissue-damaging phenotype. The ratio of Ly6C(hi)/Ly6C(low) increases when mice chronically fed ethanol were binged, which significantly enhanced liver injury. Moreover, upon phagocytosis of apoptotic hepatocytes, Ly6C(hi) IMs switch to Ly6C(low) IMs. Taken together, chronic ethanol feeding induces the recruitment of two subsets of hepatic IMs, which play different or even opposite roles in regulating liver inflammation and repair. These findings may not only increase our understanding of the complex functions of Macs in the pathogenesis of ALD but also help us to identify novel therapeutic targets for the treatment of this disease. PMID:25030420

Wang, Meng; You, Qiang; Lor, Kenton; Chen, Fangfang; Gao, Bin; Ju, Cynthia

2014-10-01

274

Molecular investigation of interspousal transmission of hepatitis C virus in two Japanese patients who acquired acute hepatitis C after 40 or 42 years of marriage.  

PubMed

A 65-year-old woman (C1I) and a 65-year-old man (C2I) contracted acute hepatitis C 40 or 42 years after marriage, respectively, in Japan. They had no discernible risk factors for acquiring hepatitis C virus (HCV) infection, except that they had monogamous sexual relationships with their spouses (C1S [66-year-old] with hepatocellular carcinoma and C2S [64-year-old] with liver cirrhosis, respectively) who were infected with HCV of the same genotype (1b) and had a high-titer HCV RNA in the serum (bDNA probe assay, 17 Meq/ml [C1S] and 15 Meq/ml [C2S]). The HCV isolates from Patients C1I and C1S and those from Patients C2I and C2S shared identity of 99.9% and 99.1%, respectively, in the 1,087-nucleotide (nt) sequence of the NS5B region, although these four isolates were only 91.7%-96.2% identical to the 94 reported genotype 1b isolates including those from Japanese patients. To confirm the high degree of genetic relatedness among ten HCV clones from each spouse within each pair of spouses, the E1 and E2 junctional region sequence (268 or 271 nt) including hypervariable region 1 (HVR-1) was analyzed. There was a close relationship between clones obtained from each spouse within each couple. Regarding the HVR-1 amino acid sequence, nine of the ten C1I clones were 100% identical with six of the ten C1S clones, and one each of the C2I and C2S clones differed by only one amino acid residue. This study indicates that two Japanese patients with acute hepatitis C had acquired HCV infection most probably by interspousal sexual transmission during a long-lasting marriage. PMID:15602741

Nakayama, Haruo; Sugai, Yoshiki; Ikeya, Shinichi; Inoue, Jun; Nishizawa, Tsutomu; Okamoto, Hiroaki

2005-02-01

275

Milk Thistle for Alcoholic and\\/or Hepatitis B or C Liver Diseases—A Systematic Cochrane HepatoBiliary Group Review with Meta-Analyses of Randomized Clinical Trials  

Microsoft Academic Search

OBJECTIVES:Our objectives were to assess the beneficial and harmful effects of milk thistle (MT) or MT constituents versus placebo or no intervention in patients with alcoholic liver disease and\\/or hepatitis B and\\/or C liver diseases.METHODS:Randomized clinical trials studying patients with alcoholic and\\/or hepatitis B or C liver diseases were included (December 2003). The randomized clinical trials were evaluated by components

Andrea Rambaldi; Bradly P. Jacobs; Gaetano Iaquinto; Christian Gluud

2005-01-01

276

Plasma Interleukin-10: A Likely Predictive Marker for Hepatitis B Virus-Related Acute-on-Chronic Liver Failure  

PubMed Central

Background: The pathogenesis of HBV-related acute-on-chronic liver failure (HBV-ACLF) is mainly based on a heightened immune-inflammatory reaction; however, the intimate underlying mechanism remains unclear. Objectives: The aim of the study was to explore potential key immune molecular targets that could serve as early predictive markers for HBV-ACLF. Patients and Methods: Twenty-seven patients with acute exacerbation of chronic hepatitis B (CHB) (defined by: alanine transaminase ? 20 ULN, total bilirubin ? 5 ULN, 40% < prothrombin time activity ? 60%) and without cirrhosis were divided into 18 cases which did not progress to HBV-ACLF (defined by: prothrombin time activity < 40% and development within four weeks of hepatic encephalopathy and/or ascites) and nine cases that developed HBV-ACLF. Nine healthy people defined the normal control group (NC). Interleukin-1? (IL-1?), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, TNF-? and IFN-? protein levels were assayed by Cytometric Bead Array (CBA) in blood plasma. The ELISA method was applied to confirm IL-10 detection using the CBA method. Results: IL-4, IL-12p70 and IFN-? were undetectable; IL-1?, IL-6, IL-8, IL-10 and TNF-? levels were significantly higher than in NC. Moreover, cytokines reached the highest levels in acute exacerbation of CHB, with the exception of IL-2 and IL-8. When comparing the HBV-ACLF patients prior to and at the time of ACLF diagnosis, IL-10 was the only cytokine that exhibited a significant decrease (P = 0.008). IL-10 concentrations were positively correlated to ALT levels (r = 0.711, P < 0.001). Conclusions: The assessment of plasma IL-10 levels in chronic hepatitis B acute exacerbation may provide an early predictive marker for progression to HBV-ACLF. PMID:25147572

Wang, Ke; Wu, Zhe-bin; Ye, Yi-nong; Liu, Jing; Zhang, Geng-lin; Su, Yu-jie; He, Hong-liang; Zheng, Yu-bao; Gao, Zhi-liang

2014-01-01

277

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

SciTech Connect

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.

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

1981-02-01

278

Nrf2 pathway activation contributes to anti-fibrosis effects of ginsenoside Rg1 in a rat model of alcohol- and CCl4-induced hepatic fibrosis  

PubMed Central

Aim: To investigate the anti-fibrosis effects of ginsenoside Rg1 on alcohol- and CCl4-induced hepatic fibrosis in rats and to explore the mechanisms of the effects. Methods: Rats were given 6% alcohol in water and injected with CCl4 (2 mL/kg, sc) twice a week for 8 weeks. Rg1 (10, 20 and 40 mg/kg per day, po) was administered in the last 2 weeks. Hepatic fibrosis was determined by measuring serum biochemical parameters, HE staining, Masson's trichromic staining, and hydroxyproline and ?-SMA immunohistochemical staining of liver tissues. The activities of antioxidant enzymes, lipid peroxidation, and Nrf2 signaling pathway-related proteins (Nrf2, Ho-1 and Nqo1) in liver tissues were analyzed. Cultured hepatic stellate cells (HSCs) of rats were prepared for in vitro studies. Results: In the alcohol- and CCl4-treated rats, Rg1 administration dose-dependently suppressed the marked increases of serum ALT, AST, LDH and ALP levels, inhibited liver inflammation and HSC activation and reduced liver fibrosis scores. Rg1 significantly increased the activities of antioxidant enzymes (SOD, GSH-Px and CAT) and reduced MDA levels in liver tissues. Furthermore, Rg1 significantly increased the expression and nuclear translocation of Nrf2 that regulated the expression of many antioxidant enzymes. Treatment of the cultured HSCs with Rg1 (1 ?mol/L) induced Nrf2 translocation, and suppressed CCl4-induced cell proliferation, reversed CCl4- induced changes in MDA, GPX, PCIII and HA contents in the supernatant fluid and ?-SMA expression in the cells. Knockdown of Nrf2 gene diminished these actions of Rg1 in CCl4-treated HSCs in vitro. Conclusion: Rg1 exerts protective effects in a rat model of alcohol- and CCl4-induced hepatic fibrosis via promoting the nuclear translocation of Nrf2 and expression of antioxidant enzymes. PMID:24976156

Li, Jian-ping; Gao, Yan; Chu, Shi-feng; Zhang, Zhao; Xia, Cong-yuan; Mou, Zheng; Song, Xiu-yun; He, Wen-bin; Guo, Xiao-feng; Chen, Nai-hong

2014-01-01

279

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

PubMed Central

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

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

2014-01-01

280

Acute Alcohol Intoxication Inhibits the Lineage-c-kit+Sca-1+ Cell Response to Escherichia Coli Bacteremia1  

PubMed Central

Alcohol abuse predisposes the host to bacterial infections. In response to bacterial infection, the bone marrow hematopoietic activity shifts toward granulocyte production which is critical for enhancing host defense. This study investigated the hematopoietic precursor cell response to bacteremia and how alcohol affects this response. Acute alcohol intoxication was induced in Balb/c mice 30 min prior to initiation of Escherichia coli bacteremia. Bacteremia caused a significant increase in the number of bone marrow lineage(lin3)-c-kit+Sca-1+ cells. Marrow lin-c-kit+Sca-1+ cells isolated from bacteremic mice showed an increase in CFU-GM activity compared to controls. In addition to enhanced proliferation of lin-c-kit+Sca-1+ cells as reflected by BrdU incorporation, phenotypic inversion of lin-c-kit+Sca-1- cells primarily accounted for the rapid increase in marrow lin-c-kit+Sca-1+ cells following bacteremia. Bacteremia increased plasma concentration of TNF-?. Culture of marrow lin-c-kit+Sca-1- cells with recombinant murine TNF-? for 24 h caused a dose dependent increase in conversion of these cells to lin-c-kit+Sca-1+ cells. Sca-1 mRNA expression by the cultured cells was also up-regulated following TNF-? stimulation. Acute alcohol intoxication inhibited the increase in the number of lin-c-kit+Sca-1+ cells in the bone marrow after E. coli infection. Alcohol impeded the increase in BrdU incorporation into marrow lin-c-kit+Sca-1+ cells in response to bacteremia. Alcohol also suppressed the plasma TNF-? response to bacteremia and inhibited TNF-?-induced phenotypic inversion of lin-c-kit+Sca-1- cells in vitro. These data show that alcohol inhibits the hematopoietic precursor cell response to bacteremia which may serve as one mechanism underlying the impaired host defense in alcohol abusers with severe bacterial infections. This is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (AAI), publisher of The JI, holds the copyright to this manuscript. This version of the manuscript has not yet been copyedited or subjected to editorial proofreading by The JI; hence, it may differ from the final version published in The JI (online and in print). AAI (The JI) is not liable for errors or omissions in this author-produced version of the manuscript or in any version derived from it by the U.S. National Institutes of Health or any other third party. The final, citable version of record can be found at www.jimmunol.org. PMID:19155505

Zhang, Ping; Welsh, David A.; Siggins, Robert W.; Bagby, Gregory J.; Raasch, Caroline E.; Happel, Kyle I.; Nelson, Steve

2009-01-01

281

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

Microsoft Academic Search

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

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

1995-01-01

282

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

PubMed Central

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

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

2014-01-01

283

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

PubMed Central

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

Philips, Cyriac Abby; Sarin, Shiv Kumar

2014-01-01

284

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

PubMed

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

Philips, Cyriac Abby; Sarin, Shiv Kumar

2014-11-21

285

Innate Immune Responses in Hepatitis C Virus Exposed Healthcare Workers Who do not Develop Acute Infection  

PubMed Central

Hepatitis C virus (HCV) infection typically results in chronic disease with HCV outpacing antiviral immune responses. Here we asked whether innate immune responses are induced in healthcare workers who are exposed to small amounts of HCV, but do not develop systemic infection and acute liver disease. Twelve healthcare workers with accidental percutaneous exposure to HCV-infected blood were prospectively studied up to 6 months for phenotype and function of NKT and NK cells, kinetics of serum chemokines, and vigor and specificity of HCV-specific T cell responses. Eleven healthcare workers tested negative for HCV RNA and HCV-antibodies. All but one of these aviremic cases displayed NKT cell activation, increased serum chemokines levels, and NK cell responses with increased CD122, NKp44, NKp46 and NKG2A expression, cytotoxicity (as determined by TRAIL and CD107a expression) and IFN-? production. This multifunctional NK cell response appeared a month earlier than in the one health care worker who developed high-level viremia, and it differed from the impaired IFN-? production, which is typical for NK cells in chronic HCV infection. The magnitude of NKT cell activation and NK cell cytotoxicity correlated with the magnitude of the subsequent HCV-specific T cell response. T cell responses targeted nonstructural HCV sequences that require translation of viral RNA, which suggests that transient or locally contained HCV replication occurred without detectable systemic viremia. Collectively, these results demonstrate that exposure to small amounts of HCV induces innate immune responses, which correlate with the subsequent HCV-specific T cell response and may contribute to antiviral immunity. PMID:23463364

Werner, Jens Martin; Heller, Theo; Gordon, Ann Marie; Sheets, Arlene; Sherker, Averell H.; Kessler, Ellen; Bean, Kathleen S.; Stevens, M'Lou; Schmitt, James; Rehermann, Barbara

2013-01-01

286

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

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

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

2014-01-01

287

Exercise and spirulina control non-alcoholic hepatic steatosis and lipid profile in diabetic Wistar rats  

Microsoft Academic Search

Background  Diabetes mellitus is associated with metabolic dysfunctions, including alterations in circulating lipid levels and fat tissue\\u000a accumulation, which causes, among other pathologies, non-alcoholic fatty liver disease (NAFLD).\\u000a \\u000a \\u000a \\u000a \\u000a Aim of the study  The objective of this study was to analyse the effects of physical exercise and spirulina intake on the control of NAFLD in diabetic Wistar rats.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Diabetes was induced in the

Leandro P Moura; Guilherme M Puga; Wladimir R Beck; Inaian P Teixeira; Carolina Ana Ghezzi; Gláucio A Silva; Maria Alice R Mello

2011-01-01

288

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

PubMed Central

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

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

2012-01-01

289

Acute Use of Alcohol and Methods of Suicide in a US National Sample  

PubMed Central

Objectives. We explored age, gender, and racial/ethnic differences with alcohol use and firearms, hanging or asphyxiation, and poisoning methods of suicide. Methods. We analyzed data for 37?993 suicide decedents aged 18 years and older from the 2005–2010 National Violent Death Reporting System database. Multinomial logistic regressions examined associations of method with alcohol use defined by blood alcohol content. Two-way interactions tested the effects of age, gender, and race/ethnicity on the associations between alcohol use and method of suicide. Results. Alcohol was present among decedents who used the 3 leading methods of suicide: firearm (35.0%), hanging (36.8%), and poisoning (32.7%). Two-way interaction tests suggested that in young and middle adulthood, individuals were more likely to drink alcohol when they used a firearm or hanging (compared with poisoning), but in older adulthood, the reverse was true, with alcohol use more likely with poisoning. Interaction tests also suggested that Asians and Pacific Islanders were most likely to use alcohol in poisonings and that Blacks were least likely to use alcohol in hangings. Conclusions. The results suggested that alcohol use before suicide was influenced by several factors, including age, race/ethnicity, and suicide method. PMID:23678938

Conner, Kenneth R.; Huguet, Nathalie; Caetano, Raul; Giesbrecht, Norman; McFarland, Bentson H.; Nolte, Kurt B.

2014-01-01

290

In the company of others: Social factors alter acute alcohol effects  

PubMed Central

Rationale Alcohol is usually consumed in social contexts. However, the drug has been studied mainly under socially isolated conditions, and our understanding of how social setting affects response to alcohol is limited. Objectives The current study compared the subjective, physiological and behavioral effects of a moderate dose of alcohol in moderate social drikers who were tested in either a social or an isolated context, and in the presence of others who had or had not consumed alcohol. Methods: Healthy men and women were randomly assigned to either a social group tested in pairs (SOC; N=24), or an isolated group tested individually (ISO; N=20). They participated in four sessions, in which they received oral alcohol (0.8 g/kg) or placebo on two sessions each, in quasi randomized order under double blind conditions. In the SOC condition, the drug conditions of the co-participants were varied systematically: On two sessions both participants received the same substance (placebo or alcohol) and on the other two sessions one received alcohol while the other received placebo. Cardiovascular measures, breath alcohol levels and mood were assessed at regular intervals, and measures of social interaction were obtained in the SOC group. Results Alcohol produced greater effects on certain subjective measures in the SOC condition compared to the ISO condition, including feelings of intoxication and stimulation, but not on other measures such as feeling sedated or high, or on cardiovascular measures. Within the SOC condition, participants rated themselves as more intoxicated when their partner received alcohol, and paired subjects interacted more when at least one participant received alcohol. Conclusions The presence of others enhances some of the subjective and behavioral effects of alcohol, especially the presence of another intoxicated individual. This enhancement of alcohol effects may explain, in part, why it is used in a social context. PMID:23712603

Kirkpatrick, Matthew G.; de Wit, Harriet

2013-01-01

291

PD-1 expression in acute hepatitis C virus (HCV) infection is associated with HCV-specific CD8 exhaustion.  

PubMed

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 acquisition of a memory phenotype and recovery of an efficient CD8 cell function in resolving HCV infections, whereas high levels were maintained when HCV persisted and HCV-specific CD8 cells remained dysfunctional. Blocking PD-1/PDL-1 interaction with an anti-PDL-1 antibody improved the capacity of expansion of virus-specific CD8 cells. PMID:16956940

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

2006-11-01

292

Acute Alcohol Intoxication Decreases Glucose Metabolism but Increases Acetate Uptake in the Human Brain  

PubMed Central

Alcohol intoxication results in marked reductions in brain glucose metabolism, which we hypothesized reflect not just its GABAergic enhancing effects but also metabolism of acetate as an alternative brain energy source. To test this hypothesis we separately assessed the effects of alcohol intoxication on brain glucose and acetate metabolism using Positron Emission Tomography (PET). We found that alcohol intoxication significantly decreased whole brain glucose metabolism (measured with FDG) with the largest decrements in cerebellum and occipital cortex and the smallest in thalamus. In contrast, alcohol intoxication caused a significant increase in [1-11C]acetate brain uptake (measured as standard uptake value, SUV), with the largest increases occurring in cerebellum and the smallest in thalamus. In heavy alcohol drinkers [1-11C]acetate brain uptake during alcohol challenge trended to be higher than in occasional drinkers (p <0.06) and the increases in [1-11C]acetate uptake in cerebellum with alcohol were positively associated with the reported amount of alcohol consumed (r=0.66, p<0.01). Our findings corroborate a reduction of brain glucose metabolism during intoxication and document an increase in brain acetate uptake. The opposite changes observed between regional brain metabolic decrements and regional increases in [1-11C]acetate uptake support the hypothesis that during alcohol intoxication the brain may rely on acetate as an alternative brain energy source and provides preliminary evidence that heavy alcohol exposures may facilitate the use of acetate as an energy substrate. These findings raise the question of the potential therapeutic benefits that increasing plasma acetate concentration (ie ketogenic diets) may have in alcoholics undergoing alcohol detoxification. PMID:22947541

Volkow, Nora D.; Kim, Sung Won; Wang, Gene-Jack; Alexoff, David; Logan, Jean; Muench, Lisa; Shea, Colleen; Telang, Frank; Fowler, Joanna S.; Wong, Christopher; Benveniste, Helene; Tomasi, Dardo

2012-01-01

293

Subjective effects and changes in steroid hormone concentrations in humans following acute consumption of alcohol  

Microsoft Academic Search

Background:\\u000a   GABAA receptors are an important site of action of endogenous neurosteroids and an important mediator of several behavioral effects of alcohol. This study examined the effects of alcohol on plasma steroid hormone concentrations on the hypothesis that the endocrine effects mediate some of the subjective effects of alcohol.\\u000a Methods:\\u000a   Thirty-two healthy subjects (17 men) with no history of a

Amira Pierucci-Lagha; Jonathan Covault; Richard Feinn; Rahul T. Khisti; Christine E. Marx; Lawrence J. Shampine; Henry R. Kranzler

2006-01-01

294

Physicochemical properties, antioxidant activities and protective effect against acute ethanol-induced hepatic injury in mice of foxtail millet (Setaria italica) bran oil.  

PubMed

This study was designed to investigate physicochemical characterization of the oil extracted from foxtail millet bran (FMBO), and the antioxidant and hepatoprotective effects against acute ethanol-induced hepatic injury in mice. GC-MS analysis revealed that unsaturated fatty acids (UFAs) account for 83.76% of the total fatty acids; in particular, the linoleic acid (C18:2) is the predominant polyunsaturated fatty acid (PUFA), and the compounds of squalene and six phytosterols (or phytostanols) were identified in unsaponifiable matter of FMBO. The antioxidant activity examination of FMBO in vitro showed highly ferric-reducing antioxidant power and scavenging effects against DPPH· and HO· radicals. Furthermore, the protective effect of FMBO against acute hepatic injuries induced by ethanol was verified in mice. In this, intragastric administration with different dosages of FMBO in mice ahead of acute ethanol administration could observably antagonize the ethanol-induced increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), and the hepatic malondialdehyde (MDA) levels, respectively, along with enhanced hepatic superoxide dismutase (SOD) levels relative to the control. Hepatic histological changes were also observed and confirmed that FMBO is capable of attenuating ethanol-induced hepatic injury. PMID:24909671

Pang, Min; He, Shujian; Wang, Lu; Cao, Xinmin; Cao, Lili; Jiang, Shaotong

2014-08-01

295

When Someone Close to You Has Chronic Hepatitis B  

MedlinePLUS

... liver disease that results from infection with the Hepatitis B virus. Hepatitis B can be “acute” or “chronic.” Acute ... the first 6 months of exposure to the Hepatitis B virus. Some people recover from their acute infection. When ...

296

Methylation of suppressor of cytokine signalling 1 gene promoter is associated with acute-on-chronic hepatitis B liver failure.  

PubMed

Suppressor of cytokine signalling 1 (SOCS1) was demonstrated to play an important negative role in fulminant hepatitis and might be involved in acute-on-chronic hepatitis B liver failure (ACHBLF). This study was therefore to identify the potential role of SOCS1 and its promoter methylation pattern in ACHBLF patients. Sixty ACHBLF patients, 60 chronic hepatitis B (CHB) patients and 30 healthy controls were investigated in this study. We found that expression of SOCS1 mRNA in CHB and ACHBLF patients was significantly higher than that in healthy controls. The serum level of IL-6, IFN-? and TNF-? was significantly higher in ACHBLF than CHB. Increased serum level of IL-6, IFN-? and TNF-? was correlated with total bilirubin, ALT, PTA and MELD scores in ACHBLF. The degree of methylation of the SOCS1 in ACHBLF patients (35.0%, 21/60) was significantly higher than that in CHB patients (16.7%, 10/60). Furthermore, methylated group showed lower level of SOCS1, and higher MELD scores and mortality rate when compared with unmethylated group of ACHBLF. These results suggested that SOCS1 might contribute to immune-related liver damage in ACHBLF, and its aberrant methylation may be a key event for the prognosis of ACHBLF. PMID:25045829

Zhang, J-J; Fan, Y-C; Zhang, Z-H; Han, J; Wang, L-Y; Li, T; Zhang, F; Yin, Y-P; Hu, L-H; Yang, Y; Sun, F-K; Wang, K

2015-03-01

297

Use of alcohol hand sanitizer as an infection control strategy in an acute care facility  

Microsoft Academic Search

Background: Nosocomial infections are a major problem in health care facilities, resulting in extended durations of care, substantial morbidity and mortality, and excess costs. Since alcohol gel hand sanitizers combine high immediate antimicrobial efficacy with ease of use, this study was carried out to determine the effect of the use of an alcohol gel hand sanitizer by caregivers on infection

Jessica Hilburn; Brian S. Hammond; Eleanor J. Fendler; Patricia A. Groziak

2003-01-01

298

sTNFR-II and sICAM-1 are associated with acute disease and hepatic inflammation in schistosomiasis japonica  

PubMed Central

Soluble intracellular adhesive molecule 1 (sICAM-1) and tumour necrosis factor receptors I (TNFR-1) and II (TNFR-II) have been shown to be associated with numerous liver disorders. Shedding of these membrane proteins can be triggered by the Th1 cytokines, TNF-alpha and IFN-gamma, which are associated with susceptibility or resistance to hepatic schistosomiasis, respectively. Further, TNF-alpha receptors and sICAM-1 have been implicated in periportal fibrosis in advanced human schistosomiasis mansoni and correlate with schistosome granuloma formation in the murine model. We measured serum levels of sICAM-1, TNFR-I and TNFR-II in Chinese patients with different clinically defined stages of schistosomiasis japonica and controls; these included 35 patients with acute schistosomiasis, 45 patients with chronic schistosome infections, 34 advanced patients with evidence of severe morbidity and 20 patients with no known history of exposure to infection. Markedly elevated levels of soluble TNFRs (sTNFRs) and sICAM-1 were observed in the acute and advanced patients compared with the chronic and control groups. Mean sTNFR-II levels were significantly higher in acute patients compared with advanced (P < 0.00001) and chronic patients (P < 0.00001) and showed the strongest association of the markers with acute disease (odds ratio (OR) = 1.099). sTNFR-II and sICAM-1 levels both correlated with infection intensity and there were significant positive correlations observed between eosinophil count and infection intensity (P = 0.0072) and sICAM-1 (P = 0.0014). Although there were significantly higher levels of antigen-specific IgG4 and total IgG in infected individuals compared with controls, none correlated with infection intensity. Further, no differences in IgG4 and total IgG levels were observed between the acute and chronic groups. The results suggest sTNFRs and sICAM-1 are associated with liver inflammation and disease progression. Measurement of sTNFR-II and sICAM-1 levels in serum could serve as additional markers for the diagnosis of acute stage disease and the monitoring of hepatic inflammation in human schistosomiasis japonica. PMID:18001742

Ellis, Magda K.; Li, Yuesheng; Hou, Xunya; Chen, Honggen; McManus, Donald P.

2008-01-01

299

Erythropoietic and hepatic porphyrias  

Microsoft Academic Search

Porphyrias are divided into erythropoietic and hepatic manifestations. Erythropoietic porphyrias are characterized by cutaneous symptoms and appear in early childhood. Erythropoietic protoporphyria is complicated by cholestatic liver cirrhosis and progressive hepatic failure in 10% of patients. Acute hepatic porphyrias (d-aminolaevulinic acid dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria and variegate porphyria) are characterized by variable extrahepatic gastrointestinal, neurological–psychiatric and

U. Gross; G. F. Hoffmann; M. O. Doss

2000-01-01

300

Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding.  

PubMed

Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to <1.0% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 ?g/g in the lungs of ethanol-fed mice as compared to 1.5 ?g/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1? and spliced XBP1 was observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. PMID:24625836

Kaphalia, Lata; Boroumand, Nahal; Hyunsu, Ju; Kaphalia, Bhupendra S; Calhoun, William J

2014-06-01

301

Acute Alcohol Consumption Impairs Controlled but Not Automatic Processes in a Psychophysical Pointing Paradigm  

PubMed Central

Numerous studies have investigated the effects of alcohol consumption on controlled and automatic cognitive processes. Such studies have shown that alcohol impairs performance on tasks requiring conscious, intentional control, while leaving automatic performance relatively intact. Here, we sought to extend these findings to aspects of visuomotor control by investigating the effects of alcohol in a visuomotor pointing paradigm that allowed us to separate the influence of controlled and automatic processes. Six male participants were assigned to an experimental “correction” condition in which they were instructed to point at a visual target as quickly and accurately as possible. On a small percentage of trials, the target “jumped” to a new location. On these trials, the participants’ task was to amend their movement such that they pointed to the new target location. A second group of 6 participants were assigned to a “countermanding” condition, in which they were instructed to terminate their movements upon detection of target “jumps”. In both the correction and countermanding conditions, participants served as their own controls, taking part in alcohol and no-alcohol conditions on separate days. Alcohol had no effect on participants’ ability to correct movements “in flight”, but impaired the ability to withhold such automatic corrections. Our data support the notion that alcohol selectively impairs controlled processes in the visuomotor domain. PMID:23861934

Johnston, Kevin; Timney, Brian; Goodale, Melvyn A.

2013-01-01

302

Severity of acute hepatitis and its outcome in patients with dengue fever in a tertiary care hospital Karachi, Pakistan (South Asia)  

Microsoft Academic Search

BACKGROUND: Liver injury due to dengue viral infection is not uncommon. Acute liver injury is a severe complicating factor in dengue, predisposing to life-threatening hemorrhage, Disseminated Intravascular Coagulation (DIC) and encephalopathy. Therefore we sought to determine the frequency of hepatitis in dengue infection and to compare the outcome (length of stay, in hospital mortality, complications) between patients of Dengue who

Om Parkash; Aysha Almas; SM Wasim Jafri; Saeed Hamid; Jaweed Akhtar; Hasnain Alishah

2010-01-01

303

Dose-response relationship between in-hospital mortality and alcohol following acute injury.  

PubMed

Although the relationship between alcohol and injury incidence is well researched, there continues to be dispute about the relationship between alcohol and mortality following an injury. Findings from past studies have varied primarily because of methodological issues and have failed to characterize the dose-response relationship. The main objective of this study was to evaluate the dose response relationship of in-hospital mortality and blood alcohol concentration (BAC). This study was a retrospective analysis of traumatic injuries occurring between 1995 and 2009 as reported by all level 1 and 2 trauma units in the State of Illinois. The study includes all patients with blood alcohol toxicological examination levels ranging from zero to 500 mg/dl (N = 190,612). The Illinois trauma registry includes all patients sustaining traumatic injuries and admitted to a trauma center for ?12 h. A total of 6733 patients meeting the inclusion criteria died following admission. Patients that were dead on arrival and those that died during the initial assessment within the emergency room were excluded. In the adjusted multivariable model, a decrease in in-hospital mortality was strongly associated with an increase in blood alcohol concentration (adjusted OR = 0.83 per 100 mg/dl units change in BAC; CI 95%: 0.80, 0.85; p < 0.001). The direction of the dose response relationship was consistent across the stratified models, with the exception of patients suffering burns. The largest reduction of in-hospital case fatality rates by blood alcohol concentration was observed among patients suffering penetrating or severe injuries (Injury Severity Score ? 16). In the clinical setting, it is important to understand not only how to recognize intoxicated patients, but also how alcohol may affect the course of treatment. The consistency of the findings across the multivariable models indicates that blood alcohol concentration is strongly associated with lower in-hospital mortality among those that survive long enough to receive treatment in specialized trauma units. PMID:23085114

Friedman, Lee S

2012-12-01

304

Comparison of Serological and Nucleic Acid Based Assays Used to Diagnose Hepatitis C Virus (HCV) Infection in Acute and Chronic Liver Diseases  

PubMed Central

Background: This study reports a comparative diagnostic potential of three different assay systems used to detect HCV infection in acute and chronic liver diseases. Methods: A total number of 364 patients with various types of liver diseases were analyzed for hepatitis C virus (HCV) core antigen using Enzyme Immuno Assay (EIA), HCV-RNA by RT-PCR and anti-HCV antibodies by third generation EIA system. Simultaneously these patients were also tested for markers of other hepatitis viruses, notably, hepatitis A, B, C, D and E. In some cases, even transfusion transmitted virus (TTV) was tested using TTV-DNA as the marker of TTV infection. Results: Analysis of results demonstrated the presence of hepatitis B, C and E in different proportions of patients belonging to these liver diseases. Hepatitis A and D infections could not be detected in these cases TTV infection was prevalent in different liver diseases in different proportions. Though none of control sera demonstrated hepatitis A-E infection, however, TTV infection was noted in control group also. When we analysed all the sera for HCV infection using these different assay systems, we found HCV core, HCV-RNA and anti-HCV antibodies in 18.3%, 18.3% and 5.83% cases of acute viral hepatitis (AVH), 13.3 %, 13.3% and 46.6% cases of chronic viral hepatitis (CVH), 23.8%, 23.8% and 23.8% cases with cirrhosis of liver and 20%, 17.5% and 10% cases respectively, of fulminant hepatic failure (FHF) patients. Whereas HCV core and HCV-RNA assays were comparable and predominantly positive in acute cases (AVH and FHF), anti-HCV antibodies were detected in high proportions in chronic liver diseases. Cirrhosis patients showed all the markers in equal proportions. This pattern of HCV markers remains unaffected by co-infection of HCV with other hepatitis viral infections. Conclusion: In conclusion, where HCV core and HCV-RNA are best diagnostic markers in acute liver diseases, anti-HCV diagnoses high proportion of HCV cases in chronic liver diseases. This diagnostic pattern is not changed on co-infection of HCV with other viral infections. PMID:21475446

Irshad, M.; Dhar, I.; Khushboo; Singh, Shiwani; Kapoor, S.

2007-01-01

305

Association of Proton Pump Inhibitor Therapy with Hepatic Encephalopathy in Hepatitis B Virus-related Acute-on-Chronic Liver Failure  

PubMed Central

Background: Hepatic encephalopathy (HE) is an important neuropsychiatry complication of acute-on-chronic liver failure (ACLF). PPI therapy may increase the intestinal bacterial overgrowth and infections. Objectives: The aim of this study was to assess whether PPI use in ACLF is associated with HE. Patients and Methods: A retrospective case-control study was performed. Fifty five admitted patients with hepatitis B virus (HBV)-related ACLF complicated by Stage II-IV HE developed after admission between January 2008 and December 2012 were matched (by sex, age, and MELD score) with comparable HBV-related ACLF patients (n = 110) who did not develop this complication during hospitalization. We excluded combined HE upon admission and other neurological disorders in patients with ACLF. Univariate and multivariate analyses of 30 variables (laboratory examination, predisposition, treatment, etc.) before the occurrence of HE were carried out to identify the factors predictive of HE. Results: In univariate analysis, patients with HE in ACLF had a significantly higher rate of PPI use (89.1%) compared with non-HE (63.6%, P = 0.001). In addition, clinical and standard laboratory variables were significantly different between the two groups regarding the infection rate, hyponatremia, alpha-fetoprotein (AFP), Arginine Hydrochloride use and Lactulose use. Logistic regression analysis was used to examine the combined effects of the variables with HE as the outcome. HE in ACLF was associated with hyponatremia (odds ratio (OR) = 6. 318, 95% confidence interval (CI) = 2. 803-14.241; P = 0. 000), PPI use was independently associated with HE (OR = 4. 392, CI = 1. 604-12.031; P = 0. 004), and lactulose use was protective (OR = 0. 294, CI = 0. 136-0.675; P = 0. 003). Conclusions: The occurrence of HE is associated with hyponatremia and PPI use in patients with ACLF. PMID:24748895

Lin, Zhao-Ni; Zuo, Yong-Qing; Hu, Peng

2014-01-01

306

Hepatic Ceramide May Mediate Brain Insulin Resistance and Neurodegeneration in Type 2 Diabetes and Non-alcoholic  

E-print Network

and Non-alcoholic Steatohepatitis Lascelles E. Lyn-Cook Jr1, Margot Lawton1, Ming Tong, Elizabeth, Providence, RI, USA Abstract Obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic steatohepatitis; neurodegeneration; non-alcoholic steatohepatitis; obesity INTRODUCTION The prevalence rates of Alzheimer's disease

Hayar, Abdallah

307

Galectin-9 and IL-21 Mediate Cross-regulation between Th17 and Treg Cells during Acute Hepatitis C  

PubMed Central

Loss of CD4 T cell help correlates with virus persistence during acute hepatitis C virus (HCV) infection, but the underlying mechanism(s) remain unknown. We developed a combined proliferation/intracellular cytokine staining assay to monitor expansion of HCV-specific CD4 T cells and helper cytokines expression patterns during acute infections with different outcomes. We demonstrate that acute resolving HCV is characterized by strong Th1/Th17 responses with specific expansion of IL-21-producing CD4 T cells and increased IL-21 levels in plasma. In contrast, viral persistence was associated with lower frequencies of IL-21-producing CD4 T cells, reduced proliferation and increased expression of the inhibitory receptors T cell immunoglobulin and mucin-domain-containing-molecule-3 (Tim-3), programmed death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) on HCV-specific CD8 T cells. Progression to persistent infection was accompanied by increased plasma levels of the Tim-3 ligand Galectin-9 (Gal-9) and expansion of Gal-9 expressing regulatory T cells (Tregs). In vitro supplementation of Tim-3high HCV-specific CD8 T cells with IL-21 enhanced their proliferation and prevented Gal-9 induced apoptosis. siRNA-mediated knockdown of Gal-9 in Treg cells rescued IL-21 production by HCV-specific CD4 T cells. We propose that failure of CD4 T cell help during acute HCV is partially due to an imbalance between Th17 and Treg cells whereby exhaustion of both CD4 and CD8 T cells through the Tim-3/Gal-9 pathway may be limited by IL-21 producing Th17 cells or enhanced by Gal-9 producing Tregs. PMID:23818845

Kared, Hassen; Fabre, Thomas; Bédard, Nathalie; Bruneau, Julie; Shoukry, Naglaa H.

2013-01-01

308

Role of IL28B Gene Polymorphism and Cell-Mediated Immunity in Spontaneous Resolution of Acute Hepatitis C  

PubMed Central

Background.?A single-nucleotide polymorphism (SNP; rs12979860) near the IL28B gene has been associated with spontaneous and treatment-induced hepatitis C virus clearance. We investigated predictors of spontaneous disease resolution in a cohort of patients with acute hepatitis C (AHC), analyzing epidemiological, clinical and virological parameters together with IL28B.rs12979860 genotypes and cell-mediated immunity (CMI). Methods.?Fifty-six symptomatic AHC patients were enrolled and followed prospectively. CMI was measured in 31 patients at multiple time points by interferon-? enzyme-linked immunospot assay and was correlated to the IL28B.rs12979860 SNP. Results.?Eighteen patients had a self-limiting AHC that was associated with female sex (P = .028), older age (P = .018), alanine aminotransferase level >1000 U/L (P = .027), total bilirubin level >7 mg/dL (P = .036), and IL28B.rs12979860 genotype CC (P = .030). In multivariate analysis, only CC genotype was independently associated with self-limiting AHC (odds ratio, 5.3; 95% confidence interval, 1.1–26.5). Patients with the CC genotype with self-limiting AHC had a stronger (P = .02) and broader (P = .013) CMI than patients with the CT genotype with chronically evolving AHC. In patients with chronically evolving disease, CC genotype was associated with a broader CMI compared to CT genotype (P = .028). A negative CMI was more frequently associated with CT genotype among persistently infected patients (P = .043) and with persistent infection among CT patients (P = .033). Conclusions.?Self-limiting AHC was independently associated with CC genotype. The correlation between IL28B.rs12979860 genotypes and CMI is suggestive of a possible important role of CMI in favoring hepatitis C virus clearance in CC patients. PMID:23784926

Spada, Enea; Amoroso, Pietro; Taliani, Gloria; Zuccaro, Ornella; Chiriacò, Piergiorgio; Maio, Patrizia; Maio, Giuseppe; Esposito, Maria Luisa; Mariano, Corrado; Rinaldi, Roberto; Bellissima, Pietro; Tosti, Maria Elena; Del Porto, Paola; Francavilla, Ruggiero; Mellace, Vincenzo; Garbuglia, Anna Rosa; Folgori, Antonella; Mele, Alfonso; Buonocore, Salvatore; Lettieri, Gennaro; Pierri, Paola; Cosco, Lucio; Ferraro, Teresa; Scognamiglio, Paola; Capobianchi, Maria Rosaria; Baldi, Ubaldo; Montesano, Franco; Audino, Giulia; De Stefano, Caterina; Caterini, Antonio; Cuccia, Mario; Girelli, Gabriella; Perrone, Paola; Laurenti, Luca; Piccolella, Enza; Scotta, Cristiano; Cortese, Riccardo; Nicosia, Alfredo; Vitelli, Alessandra

2013-01-01

309

Protective effect of Mesona procumbens against tert-butyl hydroperoxide-induced acute hepatic damage in rats.  

PubMed

The protective effect of Hsian-tsao (Mesona procumbens Hemsl.) and its active compounds on liver damage was evaluated using the model of tert-butyl hydroperoxide (t-BHP)-induced acute hepatic damage in rats. Male Sprague-Dawley rats (200 +/- 10 g) were orally pretreated with a water extract of Hsian-tsao (WEHT) (0.1, 0.5, and 1.0 g/kg) or caffeic acid (0.1 g/kg of body weight) for 13 days before a single dose of t-BHP (0.2 mmol/kg, intraperitoneally) to each animal, and the rats were sacrificed 18 h later by decapitation; blood samples were collected for the assays of serum biochemical values. The livers were excised from the animals and assayed for oxidative injury, antioxidant enzyme, and pathological histology. The result showed that the oral pretreatment of WEHT (0.1, 0.5, and 1.0 g/kg) or caffeic acid (0.10 g/kg) before t-BHP (0.2 mmol/kg) treatment significantly lowered the serum levels of the hepatic enzyme markers (alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase) and reduced oxidative stress of the liver by evaluation of malondialdehyde, glutathione, 8-hydroxy-2'-deoxyguanosine, glutathione peroxidase, and glutathione reductase. The histopathological evaluation of the rat livers showed that WEHT and caffeic acid reduced the incidence of liver lesions including cloudy swelling, pyknosis, and cytolysis induced by t-BHP in rats. On the basis of the results of this study, it can be speculated that M. procumbens protects liver against t-BHP-induced hepatic damage in rats. PMID:15212457

Yen, Gow-Chin; Yeh, Chi-Tai; Chen, Yen-Ju

2004-06-30

310

Severe Aplastic Anemia following Acute Hepatitis from Toxic Liver Injury: Literature Review and Case Report of a Successful Outcome  

PubMed Central

Hepatitis associated aplastic anemia (HAAA) is a rare syndrome in which severe aplastic anemia (SAA) complicates the recovery of acute hepatitis (AH). HAAA is described to occur with AH caused by viral infections and also with idiopathic cases of AH and no clear etiology of liver injury. Clinically, AH can be mild to fulminant and transient to persistent and precedes the onset SAA. It is assumed that immunologic dysregulation following AH leads to the development of SAA. Several observations have been made to elucidate the immune mediated injury mechanisms, ensuing from liver injury and progressing to trigger bone marrow failure with the involvement of activated lymphocytes and severe T-cell imbalance. HAAA has a very poor outcome and often requires bone marrow transplant (BMT). The findings of immune related myeloid injury implied the use of immunosuppressive therapy (IST) and led to improved survival from HAAA. We report a case of young male who presented with AH resulting from the intake of muscle building protein supplements and anabolic steroids. The liver injury slowly resolved with supportive care and after 4 months of attack of AH, he developed SAA. He was treated with IST with successful outcome without the need for a BMT. PMID:25587471

Qureshi, Kamran; Sarwar, Usman; Khallafi, Hicham

2014-01-01

311

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

PubMed

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

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

312

Xenobiotic metabolism: the effect of acute kidney injury on non-renal drug clearance and hepatic drug metabolism.  

PubMed

Acute kidney injury (AKI) is a common complication of critical illness, and evidence is emerging that suggests AKI disrupts the function of other organs. It is a recognized phenomenon that patients with chronic kidney disease (CKD) have reduced hepatic metabolism of drugs, via the cytochrome P450 (CYP) enzyme group, and drug dosing guidelines in AKI are often extrapolated from data obtained from patients with CKD. This approach, however, is flawed because several confounding factors exist in AKI. The data from animal studies investigating the effects of AKI on CYP activity are conflicting, although the results of the majority do suggest that AKI impairs hepatic CYP activity. More recently, human study data have also demonstrated decreased CYP activity associated with AKI, in particular the CYP3A subtypes. Furthermore, preliminary data suggest that patients expressing the functional allele variant CYP3A5*1 may be protected from the deleterious effects of AKI when compared with patients homozygous for the variant CYP3A5*3, which codes for a non-functional protein. In conclusion, there is a need to individualize drug prescribing, particularly for the more sick and vulnerable patients, but this needs to be explored in greater depth. PMID:24531139

Dixon, John; Lane, Katie; Macphee, Iain; Philips, Barbara

2014-01-01

313

Risk Factors for Acute Hepatitis A Infection in Korea in 2007 and 2009: A Case-Control Study  

PubMed Central

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

Seo, Joo Youn; 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

2013-01-01

314

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

PubMed Central

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

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

315

Protective Effect of Danhong Injection on Acute Hepatic Failure Induced by Lipopolysaccharide and D-Galactosamine in Mice  

PubMed Central

Acute hepatic failure (AHF), which leads to an extremely high mortality rate, has become the focus of attention in clinic. In this study, Danhong injection (DHI) was investigated to evaluate the preventive and protective effect on AHF induced by lipopolysaccharide (LPS) and D-galactosamine (GalN) in mice. For AHF induction, ICR mice were intraperitoneally injected with D-GalN (700?mg/kg) and LPS (20??g/kg). DHI was administrated twice, at 12 and 1?h, respectively, before D-GalN/LPS injection. After stimulation with D-GalN/LPS for 1 and 6?h, serum and livers were collected for analysis. We found that mice administrated with DHI displayed a higher survival rate, lower serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), glutathione S-transferase (GST), and tumor necrosis factor (TNF)-?. DHI inhibited the elevations of hepatic lipid peroxidation (malondialdehyde), caspase-8 activity, and mRNA expression levels of inflammatory cytokines (interleukin-1? and interleukin-6) increased by D-GalN/LPS in the liver. Furthermore, liver histopathological analysis indicated that the DHI group showed markedly fewer apoptotic (TUNEL positive) cells and less pathological changes than those in the AHF model group. These results provide a novel insight into the pharmacological actions of DHI as a potential candidate for treating AHF. PMID:24772178

Wang, Ying; Gao, Li-Na; Cui, Yuan-Lu; Jiang, Heng-Li

2014-01-01

316

[Alcohol intake--a two-edged sword. Part 1: metabolism and pathogenic effects of alcohol].  

PubMed

From the biomedical point of view alcohol is a Janus-faced dietary component with a dose-dependent effect varying from cardiovascular protection to cytotoxicity. Alcohol is absorbed in the upper gastrointestinal tract by passive diffusion, is quickly distributed throughout body water and is mostly eliminated through oxidation. The enzymatically-catalyzed oxidative degradation to acetaldehyde and further to acetate is primarily localized in the liver. In case of a low blood alcohol concentration (<0.5 per thousand) alcohol is predominantely metabolized by the enzyme aldehyde dehydrogenase; higher blood concentrations (>0.5 per thousand) are increasingly oxidized by the microsomal ethanoloxidizing system (MEOS). Alcohol consumption induces several metabolic reactions as well as acute effects on the central nervous system. Chronic alcohol consumption to some extent irreparably damages nearly every organ with the liver being particularly concerned. There are three stages of alcohol-induced liver disease (fatty liver, alcohol hepatitis, liver cirrhosis) and the liver damages mainly result from reaction products of alcohol degradation (acetaldehyde, NADH and reactive oxygen species). An especially dreaded clinical complication of the alcohol-induced liver disease is the hepatic encephalopathy. Its pathogenesis is a multifactorial and self-perpetuating process with the swelling of astrocytes being a crucial point. Swollen astrocytes induce several reactions such as oxidative/nitrosative stress, impaired signal transduction, protein modifications and a modified gene expression profile. The swelling of astrocytes and the change in neuronal activity are attributed to several neurotoxins, especially ammonia and aromatic amino acids. In alcohol addicted subjects multiple micronutrient deficiencies are common. The status of folic acid, thiamine, pyridoxine and zinc is especially critical. PMID:22970527

Ströhle, Alexander; Wolters, Maike; Hahn, Andreas

2012-08-01

317

Increased cytokine production is associated with acute inflammation in cirrhotic alcoholic patients  

Microsoft Academic Search

The role of cytokines in the etiology of liver injury and their contribution to the systemic manifestations that occur in patients with liver disease, are not clearly understood. Aim: To study if serum levels and in vitro blood mononuclear cell (BMC) production of IL-I? and TNF? are related to the severity of alcoholic liver cirrhosis, and identify potential factors that

Sandra Hirsch; Carlos Muñoz; María Pía de la Maza; Margarita Petermann; Marcelo López; Liana Schlesinger; Daniel Bunout

1997-01-01

318

Reduction of thyroid hormones triggers down-regulation of hepatic CYP2B through nuclear receptors CAR and TR in a rat model of acute stroke.  

PubMed

Stroke is a neurological condition and may cause changes in hepatic drug-metabolizing enzymes. Hepatic CYP2B is involved in the metabolism of a variety of centrally active substances. The purpose of this study was to investigate the possible down-regulation mechanism of hepatic CYP2B after acute stroke. Using a rat model of acute stroke induced by middle cerebral artery occlusion, we studied the influence of brain ischemia/reperfusion (I/R) injury on CYP2B expression. Effects of 3,5,3'-triiodo-L-thyronine (T3) treatment on constitutive androstane receptor (CAR) and thyroid hormone receptors (TRs, including TR? and TR?) proteins were detected in Huh7 cells. We found dramatic decreases in the levels of plasma free triiodthyronine, free thyroxine and hepatic CYP2B expression. Both CAR and retinoid X receptor alpha (RXR?) were significantly dissociated from the phenobarbital-responsive enhancer module (PBREM) of the CYP2B1 promoter in the early stages of the acute stroke. The levels of the polymer of TRs, CAR, and RXR? were time-dependently decreased after brain I/R injury. T3 regulated the CAR expression at the transcriptional level, and facilitated the translocation of TR?/? proteins as well as the binding of TRs, RXR?, and CAR to PBREM region. The reduction of thyroid hormone levels after a brain I/R injury may be the initial trigger for the down-regulation of hepatic CYP2B1 via induction of the dissociation of CAR from the TRs and from the PBREM region. Our data suggest that patients with acute ischemic stroke may have a decreased CYP2B-mediated metabolism of exogenous and endogenous compounds because of the low level of thyroid hormones. PMID:24368200

Bing, Yuntao; Zhu, Siying; Jiang, Kun; Dong, Guicheng; Li, Jie; Yang, Zheqiong; Yang, Jing; Yue, Jiang

2014-02-15

319

Protective effects of HFE7A, mouse anti-human\\/mouse Fas monoclonal antibody against acute and lethal hepatic injury induced by Jo2  

Microsoft Academic Search

HFE7A is a mouse anti-human\\/mouse Fas monoclonal antibody which, protects mice from fulminant hepatitis induced by Jo2. Herein,\\u000a we report on the mechanism of the protective effect of HFE7A against Jo2-induced acute and lethal hepatic injury. HFE7A reduced\\u000a the serum aminotransferase level which was elevated after Jo2 injection. HFE7A also inhibited caspase activation and mitochondrial\\u000a depolarization in hepatocytes derived from

Hiroko Yoshida; Kenji Watanabe; Shu Takahashi; Kimihisa Ichikawa

2010-01-01

320

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

PubMed Central

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

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

2012-01-01

321

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

PubMed Central

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

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

2008-01-01

322

Use of linear and multiple antigenic peptides in the immunodiagnosis of acute hepatitis A virus infection  

Microsoft Academic Search

The reactivities of two panels of anti-HAV human sera from geographically distinct areas (Chile and Spain) to synthetic peptides from the VP1, VP2 and VP3 hepatitis A virus capsid proteins were examined by an enzyme-linked immunosorbent assay (ELISA) procedure. Two and four branched multiple antigenic peptides (MAPs) and palmitoylated peptides were compared with free synthetic sequences for the detection of

M. J Gómara; S Riedemann; I Vega; H Ibarra; G Ercilla; I Haro

2000-01-01

323

Protective effect of Zhuyeqing liquor, a Chinese traditional health liquor, on acute alcohol-induced liver injury in mice  

PubMed Central

The study first evaluated the hepatoprotective effect of Zhuyeqing Liquor (ZYQL) against acute alcohol-induced liver injury in mice. Animals were administered orally with 50% alcohol 12 ml/kg at 4 h after the doses of ZYQL everyday for fourteen consecutive days except mice in normal group. The protective effect was evaluated by biochemical parameters including serum aspartate transaminase (AST), alanine transferase (ALT), total-bilirubin (TBIL) and reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) in liver tissue. The result were confirmed histopathologically and the expression of TNF-? in mice liver was determined by immunohistochemistry analysis. HPLC-PDA was used for phytochemical analysis of ZYQL, and the plant source of each compound was claritied by UPLC-TOF-MS. The result showed that pretreatment with ZYQL exhibited a significant protective effect by reversing the biochemical parameters and histopathological changes in a dose depended manner. HPLC analysis indicated that ZYQL contained flavonoids, iridoids, terpenoids and phenolic acids, which might be the active chemicals. This study demonstrated the hepatoprotective activity of ZYQL, thus scientifically supported the function of its health care. PMID:24090365

2013-01-01

324

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

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

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

2014-01-01

325

Alcohol and Hepatitis C  

MedlinePLUS

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326

Pharmacotherapy in Alcoholism  

Microsoft Academic Search

This review categorizes five main uses of pharmacologic agents in the treatment of alcoholism: reversing the active pharmacologic effects of alcohol; controlling withdrawal symptoms; blocking the desire for alcohol use; treating psychiatric symptoms induced by alcohol and other drugs; and treating indenpendent, but concurrent, psychopathologic conditions. No medication, including stimulants such as caffeine, has been found to acutally reverse the

Norman S. Miller

1995-01-01

327

Effects of methanol extract of Cirsium japonicum var. ussuriense and its principle, hispidulin-7-O-neohesperidoside on hepatic alcohol-metabolizing enzymes and lipid peroxidation in ethanol-treated rats.  

PubMed

Effects of the methanol extract of Cirsium japonicum var. ussuriense and hispidulin 7-O-neohesperidoside isolated from the plant on hepatic alcohol-metabolizing enzymes and lipid peroxidation were studied in rats treated with ethanol. Rats treated with 10% alcohol solution for 6 weeks were orally administered with 250 or 500 mg of methanol extract or 10 or 20 mg of hispidulin 7-O-neohesperidoside per kg body weight daily during the last week of ethanol treatment. The administration of the methanol extract of herbal plant and hispidulin 7-O-neohesperidoside in ethanol-treated rats significantly enhanced the activities of hepatic alcohol dehydrogenase, microsomal ethanol-oxidizing system and aldehyde dehydrogenase in a dose-dependent manner. The extract and the compound decreased hepatic lipid peroxidation along with an increase in hepatic content of reduced glutathione. The methanol extract and hispidulin 7-O-neohesperidoside of C. japonicum var. ussuriense also increased the activity of glutathione reductase, but had no effect on gamma-glutamylcysteine synthase. The results suggest that C. japonicum var. ussuriense may alleviate alcoholic toxicity by enhancing ethanol oxidation as well as inhibiting lipid peroxidation, and hispidulin 7-O-neohesperidoside is one of the active substances responsible for the protective effects of this plant. PMID:14750195

Park, Jong Cheol; Hur, Jong Moon; Park, Ju Gwon; Kim, Sang Cheol; Park, Jeong Ro; Choi, Seong Hee; Choi, Jong Won

2004-01-01

328

Spatio-temporal processing of words and nonwords: hemispheric laterality and acute alcohol intoxication.  

PubMed

This study examined neurofunctional correlates of reading by modulating semantic, lexical, and orthographic attributes of letter strings. It compared the spatio-temporal activity patterns elicited by real words (RW), pseudowords, orthographically regular, pronounceable nonwords (PN) that carry no meaning, and orthographically illegal, nonpronounceable nonwords (NN). A double-duty lexical decision paradigm instructed participants to detect RW while ignoring nonwords and to additionally respond to words that refer to animals (AW). Healthy social drinkers (N=22) participated in both alcohol (0.6 g/kg ethanol for men, 0.55 g/kg for women) and placebo conditions in a counterbalanced design. Whole-head MEG signals were analyzed with an anatomically-constrained MEG method. Simultaneously acquired ERPs confirm previous evidence. Spatio-temporal MEG estimates to RW and PN are consistent with the highly replicable left-lateralized ventral visual processing stream. However, the PN elicit weaker activity than other stimuli starting at ~230 ms and extending to the M400 (magnetic equivalent of N400) in the left lateral temporal area, indicating their reduced access to lexicosemantic stores. In contrast, the NN uniquely engage the right hemisphere during the M400. Increased demands on lexicosemantic access imposed by AW result in greater activity in the left temporal cortex starting at ~230 ms and persisting through the M400 and response preparation stages. Alcohol intoxication strongly attenuates early visual responses occipito-temporally overall. Subsequently, alcohol selectively affects the left prefrontal cortex as a function of orthographic and semantic dimensions, suggesting that it modulates the dynamics of the lexicosemantic processing in a top-down manner, by increasing difficulty of semantic retrieval. PMID:24565928

Marinkovic, Ksenija; Rosen, Burke Q; Cox, Brendan; Hagler, Donald J

2014-04-16

329

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

PubMed

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

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

2013-12-01

330

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

PubMed Central

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

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

2013-01-01

331

Hepatic porphyrias in children  

Microsoft Academic Search

Clinically overt hepatic porphyria is uncommon in children. The autosomal dominant acute hepatic porphyrias, acute intermittent porphyria (AIP), variegate porphyria (VP) and hereditary coproporphyria (HCP), are rarely present before puberty. Identification of asymptomatic children who have inherited these disorders is an important aspect of the management of the disease in their families and requires either enzymatic or DNA methods. Homozygous

G. H. Elder

1997-01-01

332

Serum 1H-NMR Metabolomic Fingerprints of Acute-On-Chronic Liver Failure in Intensive Care Unit Patients with Alcoholic Cirrhosis  

PubMed Central

Introduction Acute-on-chronic liver failure is characterized by acute deterioration of liver function in patients with compensated or decompensated, but stable, cirrhosis. However, there is no accurate definition of acute-on-chronic liver failure and physicians often use this term to describe different clinical entities. Metabolomics investigates metabolic changes in biological systems and identifies the biomarkers or metabolic profiles. Our study assessed the metabolomic profile of serum using proton nuclear magnetic resonance (1H-NMR) spectroscopy to identify metabolic changes related to acute-on-chronic liver failure. Patients Ninety-three patients with compensated or decompensated cirrhosis (CLF group) but stable liver function and 30 patients with cirrhosis and hospitalized for the management of an acute event who may be responsible of acute-on-chronic liver failure (ACLF group), were fully analyzed. Blood samples were drawn at admission, and sera were separated and stored at –80°C until 1H-NMR spectral analysis. Using orthogonal projection to latent-structure discriminant analyses, various metabolites contribute to the complete separation between these both groups. Results The predictability of the model was 0.73 (Q2Y) and the explained variance was 0.63 (R2Y). The main metabolites that had increased signals related to acute-on-chronic liver failure were lactate, pyruvate, ketone bodies, glutamine, phenylalanine, tyrosine, and creatinine. High-density lipids were lower in the ALCF group than in CLF group. Conclusion A serum metabolite fingerprint for acute-on-chronic liver failure, obtained with 1H-NMR, was identified. Metabolomic profiling may aid clinical evaluation of patients with cirrhosis admitted into intensive care units with acute-on-chronic liver failure, and provide new insights into the metabolic processes involved in acute impairment of hepatic function. PMID:24586615

Nahon, Pierre; Bouchemal, Nadia; Kamoun, Walid; Haouache, Hakim; Trinchet, Jean-Claude; Savarin, Philippe; Le Moyec, Laurence; Dhonneur, Gilles

2014-01-01

333

In vivo ethanol elimination in man, monkey and rat: A lack of relationship between the ethanol metabolism and the hepatic activities of alcohol and aldehyde dehydrogenases  

SciTech Connect

The in vivo ethanol elimination in human subjects, monkeys and rats was investigated after an oral ethanol dosage. After 0.4 g. ethanol/kg of body weight, ethanol elimination was much slower in human subjects than in monkeys. In order to detect a rise in monkey plasma ethanol concentrations as early as observed in human subjects, ethanol had to be administered at a dose of 3 g/kg body weight. Ethanol metabolism in rats was also much faster than in human subjects. However, human liver showed higher alcohol dehydrogenase activity and higher low Km aldehyde dehydrogenase activity than rat liver. Thus, our data suggest a lack of relationship between hepatic ethanol-metabolizing activities and the in vivo ethanol elimination rate.

Zorzano, A. (Universidad de Barcelona (Spain)); Herrera, E. (Universidad de Madrid (Spain))

1990-01-01

334

Experience of acute hepatitis C and HIV co-infection in an inner city clinic in the UK  

PubMed Central

Introduction Acute hepatitis C infection (HCV) is increasing in the HIV-infected population, particularly among men who have sex with men (MSM). Patients co-infected with HCV and HIV progress more rapidly to liver cirrhosis and are at higher risk of hepatocellular carcinoma. We looked at our management of acute HCV to assess treatment outcome. Materials and Methods We performed a retrospective and prospective case note review of HIV-HCV co-infected patients attending a large inner city sexual health clinic from 2006-to date. Acute HCV infections (less than six months) were identified and data was collected on demographics, transmission and treatment outcomes. Treatment regime was 48 weeks of weight-based ribavirin and pegylated interferon ?2a. Results Sixty-seven acute HCV infections were identified among 142 co-infected patients, all of whom were male and 66 (98.5%) were MSM. Median age at diagnosis was 37 (range 20–59) and 58 (86.6%) were White British. Sixty patients (89.6%) were genotype 1, 3 (4.5%) were genotype 4 and 2 (3.0%) were genotype 2/3. A further 2 (3.0%) were re-infections. A peak in new HCV diagnoses was seen in 2013 with 17 (25.4%). Route of transmission was sexual in all cases with 13 (19.4%) also injecting drugs, pointing to mixed transmission routes. Nine (69.2%) of these occurred in 2013. Nine (13.4%) patients cleared HCV themselves. Of the 58 who didn't clear HCV, 12 (20.7%) were lost to follow up/transferred care, 4 (6.9%) declined treatment awaiting newer agents, and 10 (17.2%) are waiting to start. A total of 32 patients started treatment. Six (18.8%) patients are currently on treatment and three (9.4%) await a final sustained virological response (SVR) test. Six out of twenty-four (25.0%) stopped treatment due to lack of response and 1 stopped due to side effects. Fifteen (62.5%) achieved SVR and 2 (8.3%) failed to achieve SVR. Eight out of ten (80.0%) patients who had an early virological response (EVR) achieved SVR. Conclusions Our data shows good treatment outcomes for acute HCV infection in HIV patients with an SVR rate of 62.5%. We've seen a steady increase in acute HCV infection, particularly in MSM injecting party drugs. Changing risk behaviours, particularly a rise in chem sex parties and club drug use, along with more anonymous partners and disclosure issues create difficulties in managing the HCV epidemic. More education is needed to raise awareness of HCV transmission and disclosure in our MSM population. PMID:25394143

Ward, Christopher; Lee, Vincent

2014-01-01

335

Opioid-mediated acute responses to alcohol: ethanol potentiates opioid actions on the guinea pig ileum.  

PubMed

Acute administration of ethanol can potentiate the inhibitory effects of exogenously administered opioids on release of acetylcholine from the guinea pig's enteric nervous system. Ethanol also appears to inhibit the release of enteric substance P by enhancing the inhibitory action of simultaneously released endogenous opioids. One consequence of this mechanism of action is that those states that result in the activation of opioid-containing systems, such as stress, might also be the conditions under which the opioid component of the actions of ethanol are the most pronounced. PMID:6192873

Gintzler, A R; Scalisi, J A

1983-06-20

336

MR imaging findings in alcoholic and nonalcoholic acute Wernicke's encephalopathy: a review.  

PubMed

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

Manzo, Gaetana; De Gennaro, Angela; Cozzolino, Attilio; Serino, Antonietta; Fenza, Giacomo; Manto, Andrea

2014-01-01

337

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

338

Prognostic Indicators for Acute Liver Failure Development and Mortality in Patients with Hepatitis A: Consecutive Case Analysis  

PubMed Central

Purpose Due to the seroepidemiological shift in hepatitis A (HA), its severity, mortality, and complications have increased in recent years. Thus, the aim of this study was to identify predictive factors associated with poor prognosis among patients with HA. Materials and Methods A total of 304 patients with HA admitted to our institution between July 2009 and June 2011 were enrolled consecutively. Patients with complications defined as acute liver failure (ALF) were evaluated, and mortality was defined as death or liver transplantation. Results The mean age of patients (204 males, 100 females) was 32 years. Eighteen (5.9%) patients had progressed to ALF. Of the patients with ALF, 10 patients (3.3%) showed spontaneous survival while 8 (2.6%) died or underwent liver transplantation. Multivariate regression analysis showed that Model for End-Stage Liver Disease (MELD) and systemic inflammatory response syndrome (SIRS) scores were significant predictive factors of ALF. Based on receiver operating characteristics (ROC) analysis, a MELD ?23.5 was significantly more predictive than a SIRS score ?3 (area under the ROC: 0.940 vs. 0.742, respectively). In addition, of patients with a MELD score ?23.5, King's College Hospital criteria (KCC) and SIRS scores were predictive factors associated with death/transplantation in multivariate analysis. Conclusion MELD and SIRS scores ?23.5 and ?3, respectively, appeared to be related to ALF development. In addition, KCC and SIRS scores ?3 were valuable in predicting mortality of patients with a MELD ?23.5. PMID:24954323

Shin, Hye Sun; Kim, Sae Pyul; Han, Sang Hoon; Kim, Do Young; Ahn, Sang Hoon; Han, Kwang-Hyub; Chon, Chae Yoon

2014-01-01

339

Reducing Liver Fat by Low Carbohydrate Caloric Restriction Targets Hepatic Glucose Production in Non-Diabetic Obese Adults with Non-Alcoholic Fatty Liver Disease  

PubMed Central

Non-alcoholic fatty liver disease (NAFLD) impairs liver functions, the organ responsible for the regulation of endogenous glucose production and thus plays a key role in glycemic homeostasis. Therefore, interventions designed to normalize liver fat content are needed to improve glucose metabolism in patients affected by NAFLD such as obesity. Objective this investigation is designed to determine the effects of caloric restriction on hepatic and peripheral glucose metabolism in obese humans with NAFLD. Methods eight non-diabetic obese adults were restricted for daily energy intake (800 kcal) and low carbohydrate (<10%) for 8 weeks. Body compositions, liver fat and hepatic glucose production (HGP) and peripheral glucose disposal before and after the intervention were determined. Results the caloric restriction reduced liver fat content by 2/3 (p = 0.004). Abdominal subcutaneous and visceral fat, body weight, BMI, waist circumference and fasting plasma triglyceride and free fatty acid concentrations all significantly decreased (p < 0.05). The suppression of post-load HGP was improved by 22% (p = 0.002) whereas glucose disposal was not affected (p = 0.3). Fasting glucose remained unchanged and the changes in the 2-hour plasma glucose and insulin concentration were modest and statistically insignificant (p > 0.05). Liver fat is the only independent variable highly correlated to HGP after the removal of confounders. Conclusion NAFLD impairs HGP but not peripheral glucose disposal; low carbohydrate caloric restriction effectively lowers liver fat which appears to directly correct the HGP impairment. PMID:25411646

Yu, Haoyong; Jia, Weiping; Guo, ZengKui

2014-01-01

340

Alcoholism & depression.  

PubMed

One out of 2 Americans report drinking on a routine basis, making the excessive consumption of alcohol the third leading cause of preventable death in America (). Alcoholism and depression are common comorbidities that home healthcare professionals frequently encounter. To achieve the best patient outcomes, alcoholism should be addressed initially. Although all age groups are at risk, alcoholism and depression occur in more than 8 percent of older adults. Prevention through identifying alcohol use early in adolescence is vital to reduce the likelihood of alcohol dependence. This article provides an overview of the long-term effects of alcohol abuse, including alcoholic cirrhosis and hepatic encephalopathy. The diagnostic criteria for substance dependence and ideas for nonthreatening screening questions to use with patients who are adolescent or older are discussed. While providing patient care, home healthcare nurses share the patient's intimate home environment. This environment is perceived as a safe haven by the patient and home care nurses can take advantage of counseling and treatment opportunities in this nonthreatening environment. PMID:23026991

Hall, Mellisa

2012-10-01

341

Lycium barbarum polysaccharides therapeutically improve hepatic functions in non-alcoholic steatohepatitis rats and cellular steatosis model  

PubMed Central

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

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

342

Acute alcohol intoxication and long-term outcome in patients with traumatic brain injury.  

PubMed

The effect of blood alcohol concentration (BAC) on outcome after traumatic brain injury (TBI) is controversial. We sought to assess the independent effect of positive BAC on long-term outcome in patients with TBI treated in the intensive care unit (ICU). We performed a retrospective analysis of 405 patients with TBI, admitted to the ICU of a large urban Level 1 trauma center between January 2009 and December 2012. Outcome was six-month mortality and unfavorable neurological outcome (defined as a Glasgow Outcome Scale score of 1 [death], 2, [vegetative state], or 3 [severe disability]). Patients were categorized by admission BAC into: no BAC (0.0‰; n=99), low BAC (<2.3‰; n=140) and high BAC (?2.3‰; n=166). Logistic regression analysis, adjusting for baseline risk and severity of illness, was used to assess the independent effect of BAC on outcome (using the no BAC group as the reference). Overall six-month mortality was 25% and unfavorable outcome was 46%. Multivariate analysis showed low BAC to independently reduce risk of six-month mortality compared with no BAC (low BAC adjusted odds ratio [AOR] 0.41, 95% confidence interval [CI] 0.19-0.88, p=0.021) and high BAC (AOR 0.58, 95% CI 0.29-1.15, p=0.120). Furthermore, a trend towards reduced risk of six-month unfavorable neurological outcome for patients with positive BAC, compared to patients with negative BAC, was noted, although this did not reach statistical significance (low BAC AOR 0.65, 95% CI 0.34-1.22, p=0.178, and high BAC AOR 0.59, 95% CI 0.32-1.09, p=0.089). In conclusion, low admission BAC (<2.3‰) was found to independently reduce risk of six-month mortality for patients with TBI, and a trend towards improved long-term neurological outcome was found for BAC-positive patients. The role of alcohol as a neuroprotective agent warrants further studies. PMID:25010885

Raj, Rahul; Skrifvars, Markus B; Kivisaari, Riku; Hernesniemi, Juha; Lappalainen, Jaakko; Siironen, Jari

2015-01-15

343

Zn(II)-curcumin protects against hemorheological alterations, oxidative stress and liver injury in a rat model of acute alcoholism.  

PubMed

Curcumin can chelate metal ions, forming metallocomplexes. We compared the effects of Zn(II)-curcumin with curcumin against hemorheological alterations, oxidative stress and liver injury in a rat model of acute alcoholism. Oral administration of Zn(II)-curcumin dose-dependently prevented the ethanol-induced elevation of serum malondialdehyde (MDA) content and reductions in glutathione level and superoxide dismutase (SOD) activity. Zn(II)-curcumin also inhibited ethanol-induced liver injury. Additionally, Zn(II)-curcumin dose-dependently inhibited hemorheological abnormalities, including the ethanol-induced elevation of whole blood viscosity, plasma viscosity, blood viscosity at corrected hematocrit (45%), erythrocyte aggregation index, erythrocyte rigidity index and hematocrit. Compared to curcumin at the same dose, Zn(II)-curcumin more effectively elevated SOD activity, ameliorated liver injury and improved hemorheological variables. These results suggest that Zn(II)-curcumin protected the rats from ethanol-induced liver injury and hemorheological abnormalities via the synergistic effect of curcumin and zinc. PMID:24607687

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

2014-03-01

344

Acute Renal and Hepatic Failure in an Adolescent: An Unusual Presentation of Multiple Aortic Aneurysms.  

PubMed

Aortic dissection secondary to thoracoabdominal aortic aneurysms is very uncommon in children, and this life-threatening diagnosis requires a high clinical index of suspicion. Unlike adults, in whom atherosclerosis, inflammation, and advanced age are typically contributing factors, aortic dissection in children is usually due to nonatherosclerotic causes.Aortic aneurysms can be asymptomatic when small but, when significantly enlarged, can compromise organ function and dissect, resulting in high mortality rates. It is therefore critical that children with this uncommon condition be identified early when medical or surgical management can potentially improve outcome. We describe a 15-year-old patient with multiple aortic aneurysms with dissection whose presentation includes chronic anemia, acute-on-chronic renal failure with hyperkalemia, and liver injury. PMID:25411855

Wadia, Rajeev S; Schwartz, Jamie M; Kudchadkar, Sapna R

2014-11-19

345

Multicentre study of acute alcohol use and non-fatal injuries: data from the WHO collaborative study on alcohol and injuries.  

PubMed Central

OBJECTIVES: To study the risk of non-fatal injury at low levels and moderate levels of alcohol consumption as well as the differences in risk across modes of injury and differences among alcoholics. METHODS: Data are from patients aged 18 years and older collected in 2001-02 by the WHO collaborative study on alcohol and injuries from 10 emergency departments around the world (n = 4320). We used a case-crossover method to compare the use of alcohol during the 6 hours prior to the injury with the use of alcohol during same day of the week in the previous week. FINDINGS: The risk of injury increased with consumption of a single drink (odds ratio (OR) = 3.3; 95% confidence interval = 1.9-5.7), and there was a 10-fold increase for participants who had consumed six or more drinks during the previous 6 hours. Participants who had sustained intentional injuries were at a higher risk than participants who had sustained unintentional injuries. Patients who had no symptoms of alcohol dependence had a higher OR. CONCLUSION: Since low levels of drinking were associated with an increased risk of sustaining a non-fatal injury, and patients who are not dependent on alcohol may be at higher risk of becoming injured, comprehensive strategies for reducing harm should be implemented for all drinkers seen in emergency departments. PMID:16799729

Borges, Guilherme; Cherpitel, Cheryl; Orozco, Ricardo; Bond, Jason; Ye, Yu; Macdonald, Scott; Rehm, Jürgen; Poznyak, Vladimir

2006-01-01

346

Prolonged oval cell proliferation with Ito cell activation and extracellular matrix accumulation in galactosamine-induced acute hepatitis in mini rats.  

PubMed

Histopathological and immunohistochemical studies were carried out on D-galactosamine (GalNAc)-induced acute hepatitis in rats of the JCI: Wistar TgN (ARGHGEN) 1 Nts strain (Mini rats), in which expression of the growth hormone gene is suppressed by an antisense transgene. Hepatitis characterized by hepatocellular acidophilic necrosis with inflammatory cell infiltration was most prominent at 2 days after GalNAc (1000 mg/kg)-injection, when proliferation of Ito cells and deposition of fibronectin and laminin were found along the sinusoidal linings. At 72 hours after GalNAc-injection, Ito cell proliferation with deposition of laminin and fibronectin became more prominent, and marked proliferation of small epithelial cells was observed in the periportal area. At 7 days after GalNAc-injection, quite a number of alpha-smooth muscle actin-positive Ito cells, surrounded by abundant fibronectin, laminin and type IV collagen, were still observed in close juxtaposition to rapidly proliferating small epithelial cells. The small epithelial cells were found to be positive for both alpha-fetoprotein and cytokeratin 7 and were therefore considered to be so-called oval cells. The results suggest that there may be some relation between oval cell proliferation, Ito cell activation and extracellular matrix accumulation in GalNAc-induced acute hepatitis in Mini rats. PMID:9302554

Uetsuka, K; Suzuki, M; Nakayama, H; Doi, K

1997-10-01

347

Limited theraputic effect of n-acetylcysteine on hepatic insulin resistance in an experimental model of alcohol-induced steatohepatitis  

Technology Transfer Automated Retrieval System (TEKTRAN)

Alcohol-related steatohepatitis is associated with increased oxidative stress, DNA damage, lipotoxicity, and insulin resistance in liver. Hypothesis: Since inflammation and oxidative stress can promote insulin resistance, effective treatment with anti-oxidants, e.g. N-acetylcysteine (NAC), may rest...

348

Protective effects of HFE7A, mouse anti-human/mouse Fas monoclonal antibody against acute and lethal hepatic injury induced by Jo2  

PubMed Central

HFE7A is a mouse anti-human/mouse Fas monoclonal antibody which, protects mice from fulminant hepatitis induced by Jo2. Herein, we report on the mechanism of the protective effect of HFE7A against Jo2-induced acute and lethal hepatic injury. HFE7A reduced the serum aminotransferase level which was elevated after Jo2 injection. HFE7A also inhibited caspase activation and mitochondrial depolarization in hepatocytes derived from apoptosis induced by Jo2 injection. The protective effect of HFE7A against Jo2-induced apoptosis in mouse hepatocytes was reproducible in vitro. The cell death and caspase activation in isolated mouse hepatocytes were induced by incubating these cells with Jo2 in vitro, and HFE7A inhibited the cell death and caspase activation in mouse hepatocytes in a dose-dependent manner. The affinity of HFE7A to mouse Fas was lower than that of Jo2. The binding of Jo2 to neither recombinant mouse Fas nor mouse hepatocytes was inhibited by an excessive amount of HFE7A. Interestingly, HFE7A bound to hepatocytes isolated from Fas knockout mice. From these results, it is suggested that HFE7A may exert a protective effect against Jo2-induced hepatitis not by competitively inhibiting the binding of Jo2 to Fas on hepatocytes, and that a distinct molecule other than Fas may possibly be involved in the protective effect of HFE7A against Jo2-induced hepatic injury. PMID:20024619

Watanabe, Kenji; Takahashi, Shu; Ichikawa, Kimihisa

2009-01-01

349

Hypertonic saline resuscitation enhances blood pressure recovery and decreases organ injury following hemorrhage in acute alcohol intoxicated rodents  

PubMed Central

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

Sulzer, Jesse K.; Whitaker, Annie M.; Molina, Patricia E.

2012-01-01

350

Frontal electroencephalogram variables are associated with the outcome and stage of hepatic encephalopathy in acute liver failure.  

PubMed

Acute liver failure (ALF) and hepatic encephalopathy (HE) can lead to an elevated intracranial pressure (ICP) and death within days. The impaired liver function increases the risks of invasive ICP monitoring, whereas noninvasive methods remain inadequate. The purpose of our study was to explore reliable noninvasive methods of neuromonitoring for patients with ALF in the intensive care unit (ICU) setting; more specifically, we wanted to track changes in HE and predict the outcomes of ALF patients treated with albumin dialysis. The study included 20 patients with severe ALF at admission who had been referred to the ICU of the liver transplantation (LT) center for albumin dialysis treatment and evaluation for transplantation. Data were collected from all study patients in the form of continuous frontal electroencephalography (EEG) recordings and transcranial Doppler (TCD) measurements of cerebral blood flow. Among the studied EEG variables, the 50% spectral edge frequency decreased and the delta power increased as the HE stage increased. Both variables were predictive of the stage of HE [prediction probability (PK) of 50% spectral edge frequency?=?0.23, standard error (SE)?=?0.03; PK of delta power?=?0.76, SE?=?0.03]. The total wavelet subband entropy, a novel variable that we used for tracking abnormal EEG activity, predicted the outcome of ALF patients treated with albumin dialysis (PK?=?0.88, SE?=?0.09). With a threshold value of 1.6, the TCD pulsatility index had an odds ratio of 1.1 (95% confidence interval?=?0.1-9.3) for a poor outcome (LT or death). In conclusion, EEG variables are useful for the monitoring of HE and can be used to predict outcomes of ALF. TCD measurements do not predict patient outcomes. PMID:24975240

Stewart, Juhani; Särkelä, Mika; Koivusalo, Anna-Maria; Wennervirta, Johanna; Salmi, Tapani; Isoniemi, Helena; Stenman, Ulf-Håkan; Viertiö-Oja, Hanna; Lapinlampi, Petteri; Lindgren, Leena; Salminen, Ulla-Stina; Vakkuri, Anne

2014-10-01

351

Seven Novel Mutations in Bulgarian Patients with Acute Hepatic Porphyrias (AHP).  

PubMed

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

Dragneva, Sonya; Szyszka-Niagolov, Monika; Ivanova, Aneta; Mateva, Lyudmila; Izumi, Rumiko; Aoki, Yoko; Matsubara, Yoichi

2014-01-01

352

CD4+ T-Cell Help Is Required for Effective CD8+ T Cell-Mediated Resolution of Acute Viral Hepatitis in Mice  

PubMed Central

Cytotoxic CD8+ T cells are essential for the control of viral liver infections, such as those caused by HBV or HCV. It is not entirely clear whether CD4+ T-cell help is necessary for establishing anti-viral CD8+ T cell responses that successfully control liver infection. To address the role of CD4+ T cells in acute viral hepatitis, we infected mice with Lymphocytic Choriomeningitis Virus (LCMV) of the strain WE; LCMV-WE causes acute hepatitis in mice and is cleared from the liver by CD8+ T cells within about two weeks. The role of CD4+ T-cell help was studied in CD4+ T cell-lymphopenic mice, which were either induced by genetic deficiency of the major histocompatibility (MHC) class II transactivator (CIITA) in CIITA?/? mice, or by antibody-mediated CD4+ cell depletion. We found that CD4+ T cell-lymphopenic mice developed protracted viral liver infection, which seemed to be a consequence of reduced virus-specific CD8+ T-cell numbers in the liver. Moreover, the anti-viral effector functions of the liver-infiltrating CD8+ T cells in response to stimulation with LCMV peptide, notably the IFN-? production and degranulation capacity were impaired in CIITA?/? mice. The impaired CD8+ T-cell function in CIITA?/? mice was not associated with increased expression of the exhaustion marker PD-1. Our findings indicate that CD4+ T-cell help is required to establish an effective antiviral CD8+ T-cell response in the liver during acute viral infection. Insufficient virus control and protracted viral hepatitis may be consequences of impaired initial CD4+ T-cell help. PMID:24466045

Trautmann, Tanja; Kozik, Jan-Hendrik; Carambia, Antonella; Richter, Kirsten; Lischke, Timo; Schwinge, Dorothee; Mittrücker, Hans-Willi; Lohse, Ansgar W.; Oxenius, Annette; Wiegard, Christiane; Herkel, Johannes

2014-01-01

353

TLR3/4 signaling is mediated via the NF?B-CXCR4/7 pathway in human alcoholic hepatitis and non-alcoholic steatohepatitis which formed Mallory-Denk bodies.  

PubMed

Activation of Toll-like receptor (TLR) signaling which stimulates inflammatory and proliferative pathways is the key element in the pathogenesis of Mallory-Denk bodies (MDBs) in mice fed DDC. However, little is known as to how TLR signaling is regulated in MDB formation during chronic liver disease development. The first systematic study of TLR signaling pathway transcript regulation in human archived formalin-fixed, paraffin-embedded (FFPE) liver biopsies with MDB formation is presented here. When compared to the activation of Toll-like signaling in alcoholic hepatitis (AH) and non-alcoholic steatohepatitis (NASH) patients, striking similarities and obvious differences were observed. Similar TLRs (TLR3 and TLR4, etc.), TLR downstream adaptors (MyD88 and TRIF, etc.) and transcript factors (NF?B and IRF7, etc.) were all upregulated in the patients' livers. MyD88, TLR3 and TLR4 were significantly induced in the livers of AH and NASH compared to normal subjects, while TRIF and IRF7 mRNA were only slightly upregulated in AH patients. This is a different pathway from the induction of the TLR4-MyD88-independent pathway in the AH and NASH patients with MDBs present. Importantly, chemokine receptor 4 and 7 (CXCR4/7) mRNAs were found to be induced in the patients livers in FAT10 positive hepatocytes. The CXCR7 pathway was significantly upregulated in patients with AH and the CXCR4 was markedly upregulated in patients with NASH, indicating that CXCR4/7 is crucial in liver MDB formation. This data constitutes the first demonstration of the upregulation of the MyD88-dependent TLR4/NF?B pathway in AH and NASH where MDBs formed, via the NF?B-CXCR4/7 pathway, and provides further insight into the mechanism of MDB formation in human liver diseases. PMID:24997224

Liu, Hui; Li, Jun; Tillman, Brittany; Morgan, Timothy R; French, Barbara A; French, Samuel W

2014-10-01

354

Reduction of endotoxin attenuates liver fibrosis through suppression of hepatic stellate cell activation and remission of intestinal permeability in a rat non-alcoholic steatohepatitis model.  

PubMed

Previous clinical studies have demonstrated that endotoxin/toll?like receptor 4 (TLR4) signaling is critical in the inflammatory pathways associated with non?alcoholic steatohepatitis (NASH). In human and animal studies, NASH was associated with portal lipopolysaccharide (LPS) and the plasma LPS level was hypothesized to be associated with small intestinal bacterial overgrowth, change in composition of the microbiota and increased intestinal permeability. The aim of the present study was to investigate the roles of endogenous endotoxin and TLR4 in the pathogenesis of NASH. The effects of antibiotics were assessed in vivo using a choline deficiency amino acid (CDAA)?induced experimental liver fibrosis model. Antibiotics, including polymyxins and neomycins, were orally administered in drinking water. Antibiotics attenuated hepatic stellate cell (HSC) activation and liver fibrosis via TGF?? and collagen in an experimental hepatic fibrosis model. The mechanism by which antibiotics attenuated LPS?TLR4 signaling and liver fibrosis was assessed. Notably, TLR4 mRNA level in the liver was elevated in the CDAA group and the CDAA?induced increase was significantly reduced by antibiotics. However, no significant differences were observed in the intestine among all groups. Elevated mRNA levels of LPS binding protein, which was correlated with serum endotoxin levels, were recognized in the CDAA group and the CDAA?induced increase was significantly reduced by antibiotics. The intestinal permeability of the CDAA group was increased compared with the choline?supplemented amino acid group. The tight junction protein (TJP) in the intestine, determined by immunohistochemical analysis was inversely associated with intestinal permeability. Antibiotics improved the intestinal permeability and enhanced TJP expression. Inhibition of LPS?TLR4 signaling with antibiotics attenuated liver fibrosis development associated with NASH via the inhibition of HSC activation. These results indicated that reduction of LPS and restoration of intestinal TJP may be a novel therapeutic strategy for treatment of liver fibrosis development in NASH. PMID:25421042

Douhara, Akitoshi; Moriya, Kei; Yoshiji, Hitoshi; Noguchi, Ryuichi; Namisaki, Tadashi; Kitade, Mitsuteru; Kaji, Kosuke; Aihara, Yosuke; Nishimura, Norihisa; Takeda, Kosuke; Okura, Yasushi; Kawaratani, Hideto; Fukui, Hiroshi

2015-03-01

355

Reduction of endotoxin attenuates liver fibrosis through suppression of hepatic stellate cell activation and remission of intestinal permeability in a rat non-alcoholic steatohepatitis model  

PubMed Central

Previous clinical studies have demonstrated that endotoxin/toll-like receptor 4 (TLR4) signaling is critical in the inflammatory pathways associated with non-alcoholic steatohepatitis (NASH). In human and animal studies, NASH was associated with portal lipopolysaccharide (LPS) and the plasma LPS level was hypothesized to be associated with small intestinal bacterial overgrowth, change in composition of the microbiota and increased intestinal permeability. The aim of the present study was to investigate the roles of endogenous endotoxin and TLR4 in the pathogenesis of NASH. The effects of antibiotics were assessed in vivo using a choline deficiency amino acid (CDAA)-induced experimental liver fibrosis model. Antibiotics, including polymyxins and neomycins, were orally administered in drinking water. Antibiotics attenuated hepatic stellate cell (HSC) activation and liver fibrosis via TGF-? and collagen in an experimental hepatic fibrosis model. The mechanism by which antibiotics attenuated LPS-TLR4 signaling and liver fibrosis was assessed. Notably, TLR4 mRNA level in the liver was elevated in the CDAA group and the CDAA-induced increase was significantly reduced by antibiotics. However, no significant differences were observed in the intestine among all groups. Elevated mRNA levels of LPS binding protein, which was correlated with serum endotoxin levels, were recognized in the CDAA group and the CDAA-induced increase was significantly reduced by antibiotics. The intestinal permeability of the CDAA group was increased compared with the choline-supplemented amino acid group. The tight junction protein (TJP) in the intestine, determined by immunohistochemical analysis was inversely associated with intestinal permeability. Antibiotics improved the intestinal permeability and enhanced TJP expression. Inhibition of LPS-TLR4 signaling with antibiotics attenuated liver fibrosis development associated with NASH via the inhibition of HSC activation. These results indicated that reduction of LPS and restoration of intestinal TJP may be a novel therapeutic strategy for treatment of liver fibrosis development in NASH. PMID:25421042

DOUHARA, AKITOSHI; MORIYA, KEI; YOSHIJI, HITOSHI; NOGUCHI, RYUICHI; NAMISAKI, TADASHI; KITADE, MITSUTERU; KAJI, KOSUKE; AIHARA, YOSUKE; NISHIMURA, NORIHISA; TAKEDA, KOSUKE; OKURA, YASUSHI; KAWARATANI, HIDETO; FUKUI, HIROSHI

2015-01-01

356

Evaluation of SSYA10-001 as a replication inhibitor of severe acute respiratory syndrome, mouse hepatitis, and Middle East respiratory syndrome coronaviruses.  

PubMed

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

Adedeji, Adeyemi O; Singh, Kamalendra; Kassim, Ademola; Coleman, Christopher M; Elliott, Ruth; Weiss, Susan R; Frieman, Matthew B; Sarafianos, Stefan G

2014-08-01

357

Epitope mapping of antibodies directed against hypervariable region 1 in acute self-limiting and chronic infections due to hepatitis C virus.  

PubMed Central

Epitopes of hypervariable region 1 (HVR1) were mapped by enzyme-linked immunosorbent assay using follow-up sera of patients, all of whom were infected with the same isolate of hepatitis C virus (HCV). Our results suggest that (i) an early appearance (up to month 13 postinfection) of antibodies directed to the N terminus of HVR1 is associated with acute self-limiting infections of HCV and (ii) isolate-independent antibodies which are mainly directed to the C terminus of HVR1 seem to persist in chronically infected patients. The relevance of HVR1-specific antibodies for neutralization was evaluated by characterization of a rabbit serum. PMID:9094694

Zibert, A; Kraas, W; Meisel, H; Jung, G; Roggendorf, M

1997-01-01

358

Metabolic syndrome and hepatic resection: improving outcome  

PubMed Central

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

Agrawal, Shefali; Daruwala, Cherag

2011-01-01

359

Alcoholic liver disease: treatment.  

PubMed

The excess consumption of alcohol is associated with alcoholic liver diseases (ALD). ALD is a major healthcare problem, personal and social burden, and significant reason for economic loss worldwide. The ALD spectrum includes alcoholic fatty liver, alcoholic hepatitis, cirrhosis, and the development of hepatocellular carcinoma. The diagnosis of ALD is based on a combination of clinical features, including a history of significant alcohol intake, evidence of liver disease, and laboratory findings. Abstinence is the most important treatment for ALD and the treatment plan varies according to the stage of the disease. Various treatments including abstinence, nutritional therapy, pharmacological therapy, psychotherapy, and surgery are currently available. For severe alcoholic hepatitis, corticosteroid or pentoxifylline are recommended based on the guidelines. In addition, new therapeutic targets are being under investigation. PMID:25278689

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

2014-09-28

360

Acute effects of alcohol on cardiovascular reactivity to stress in college-age Type A (coronary prone) individuals  

Microsoft Academic Search

Healthy college-age males and females classified as Type A or Type B were randomly assigned to an alcohol (N=24) or a no-alcohol condition (N=24). Subjects were exposed to a verbal stress quiz while blood pressure, heart rate, peripheral vascular response (PVR), and self-reported anxiety indices were monitored. Results indicated that alcohol effected a reduction in resting levels of systolic blood

Amos Zeichner; Patrick Edwards; Enid Cohen

1985-01-01

361

Are oxidative stress mechanisms the common denominator in the progression from hepatic steatosis towards non-alcoholic steatohepatitis (NASH)?  

PubMed

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

Tariq, Zoon; Green, Charlotte J; Hodson, Leanne

2014-08-01

362

Effect of nutritional counselling on hepatic, muscle and adipose tissue fat content and distribution in non-alcoholic fatty liver disease  

PubMed Central

AIM: To assess the effectiveness of the current UK clinical practice in reducing hepatic fat (IHCL). METHODS: Whole body MRI and 1H MRS were obtained, before and after 6 mo nutritional counselling, from liver, soleus and tibialis muscles in 10 subjects with non-alcoholic fatty liver disease (NAFLD). RESULTS: A 500 Kcal-restricted diet resulted in an average weight loss of 4% (-3.4 kg,) accompanied by significant reductions in most adipose tissue (AT) depots, including subcutaneous (-9.9%), abdominal subcutaneous (-10.2%) and intra-abdominal-AT (-11.4%). Intramyocellular lipids (IMCL) were significantly reduced in the tibialis muscle (-28.2%). Decreases in both IHCL (-39.9%) and soleus IMCL (-12.2%) content were also observed, although these were not significant. Several individuals showed dramatic decreases in IHCL, while others paradoxically showed increases in IHCL content. Changes in body composition were accompanied by improvements in certain liver function tests: serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Significant correlations were found between decreases in IHCL and reductions in both intra-abdominal and abdominal subcutaneous AT. Improvements in liver function tests were associated with reductions in intra-abdominal AT, but not with changes in IHCL. CONCLUSION: This study shows that even a very modest reduction in body weight achieved through lifestyle modification can result in changes in body fat depots and improvements in LFTs. PMID:17007047

Thomas, E Louise; Brynes, Audrey E; Hamilton, Gavin; Patel, Nayna; Spong, Adam; Goldin, Robert D; Frost, Gary; Bell, Jimmy D; Taylor-Robinson, Simon D

2006-01-01

363

The Relationship of Alcohol Concentration in Epidural or Acute Subdural Hematoma Compared with Vitreous Humor and Femoral Blood  

Microsoft Academic Search

The study of the relationship between the epidural hematoma or subdural hematoma alcohol concen- tration (SDHAC) compared with femoral blood (BAC) and vitreous humor alcohol concentration (VHAC). The specimens of 25 corpses (total 888 corpses) were carried out which revealed EDH or SDH, no treatment and the autopsy performed within 24 hours after death in 2006 at the Forensic Medicine

2008-01-01

364

Acute effects of alcohol on stimulus-induced gamma oscillations in human primary visual and motor cortices  

PubMed Central

Alcohol is a rich drug affecting both the ?-amino butyric acid (GABA) and glutamatergic neurotransmitter systems. Recent findings from both modelling and pharmacological manipulation have indicated a link between GABAergic activity and oscillations measured in the gamma frequency range (30-80Hz), but there are no previous reports of alcohol’s modulation of gamma-band activity measured by magnetoencephalography (MEG) or electroencephalography (EEG). In this single-blind, placebo-controlled crossover study, 16 participants completed two study days, one in which they consumed a dose of 0.8g/kg alcohol, and the other a placebo. MEG recordings of brain activity were taken before and after beverage consumption, using visual grating and finger abduction paradigms known to induce gamma-band activity in the visual and motor cortices respectively. Time-frequency analyses of beamformer source reconstructions in the visual cortex showed that alcohol increased peak gamma amplitude and decreased peak frequency. For the motor task, alcohol increased gamma amplitude in the motor cortex. These data support the notion that gamma oscillations are dependent, in part, on the balance between excitation and inhibition. Disruption of this balance by alcohol, through increasing GABAergic inhibition at GABAA receptors and decreasing glutamatergic excitation at NMDA receptors, alters both the amplitude and frequency of gamma oscillations. The findings provide further insight into the neuropharmacological action of alcohol. PMID:24622470

Campbell, Anne Eileen; Sumner, Petroc; Singh, Krish D.; Muthukumaraswamy, Suresh D.

2014-01-01

365

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

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

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

366

Decreased activity of folate transporters in lipid rafts resulted in reduced hepatic folate uptake in chronic alcoholism in rats.  

PubMed

Folic acid is an essential nutrient that is required for one-carbon biosynthetic processes and for methylation of biomolecules. Deficiency of this micronutrient leads to disturbances in normal physiology of cell. Chronic alcoholism is well known to be associated with folate deficiency, which is due in part to folate malabsorption. The present study deals with the regulatory mechanisms of folate uptake in liver during chronic alcoholism. Male Wistar rats were fed 1 g/kg body weight/day ethanol (20 % solution) orally for 3 months, and the molecular mechanisms of folate uptake were studied in liver. The characterization of the folate transport system in liver basolateral membrane (BLM) suggested it to be a carrier mediated and acidic pH dependent, with the major involvement of proton coupled folate transporter and folate binding protein in the uptake. The folate transporters were found to be associated with lipid raft microdomain of liver BLM. Moreover, ethanol ingestion decreased the folate transport by altering the Vmax of folate transport process and downregulated the expression of folate transporters in lipid rafts. The decreased transporter levels were associated with reduced protein and mRNA levels of these transporters in liver. The deranged folate uptake together with reduced folate transporter levels in lipid rafts resulted in reduced folate levels in liver and thereby to its reduced levels in serum of ethanol-fed rats. The chronic ethanol ingestion led to decreased folate uptake in liver, which was associated with the decreased number of transporter molecules in the lipid rafts that can be ascribed to the reduced synthesis of these transporters. PMID:22956120

Wani, Nissar Ahmad; Nada, Ritambhara; Khanduja, Krishan Lal; Kaur, Jyotdeep

2013-03-01

367

Involvement of the TNF and FasL Produced by CD11b Kupffer Cells/Macrophages in CCl4-Induced Acute Hepatic Injury  

PubMed Central

We previously reported that F4/80+ Kupffer cells are subclassified into CD68+ Kupffer cells with phagocytic and ROS producing capacity, and CD11b+ Kupffer cells with cytokine-producing capacity. Carbon tetrachloride (CCl4)-induced hepatic injury is a well-known chemical-induced hepatocyte injury. In the present study, we investigated the immunological role of Kupffer cells/macrophages in CCl4-induced hepatitis in mice. The immunohistochemical analysis of the liver and the flow cytometry of the liver mononuclear cells showed that clodronate liposome (c-lipo) treatment greatly decreased the spindle-shaped F4/80+ or CD68+ cells, while the oval-shaped F4/80+ CD11b+ cells increased. Notably, severe hepatic injury induced by CCl4 was further aggravated by c-lipo-pretreatment. The population of CD11b+ Kupffer cells/macrophages dramatically increased 24 hour (h) after CCl4 administration, especially in c-lipo-pretreated mice. The CD11b+ Kupffer cells expressed intracellular TNF and surface Fas-ligand (FasL). Furthermore, anti-TNF Ab pretreatment (which decreased the FasL expression of CD11b+ Kupffer cells), anti-FasL Ab pretreatment or gld/gld mice attenuated the liver injury induced by CCl4. CD1d?/? mouse and cell depletion experiments showed that NKT cells and NK cells were not involved in the hepatic injury. The adoptive transfer and cytotoxic assay against primary cultured hepatocytes confirmed the role of CD11b+ Kupffer cells in CCl4-induced hepatitis. Interestingly, the serum MCP-1 level rapidly increased and peaked at six h after c-lipo pretreatment, suggesting that the MCP-1 produced by c-lipo-phagocytized CD68+ Kupffer cells may recruit CD11b+ macrophages from the periphery and bone marrow. The CD11b+ Kupffer cells producing TNF and FasL thus play a pivotal role in CCl4-induced acute hepatic injury. PMID:24667392

Sato, Atsushi; Nakashima, Hiroyuki; Nakashima, Masahiro; Ikarashi, Masami; Nishiyama, Kiyoshi; Kinoshita, Manabu; Seki, Shuhji

2014-01-01

368

Increased ethane exhalation, an in vivo index of lipid peroxidation, in alcohol-abusers  

Microsoft Academic Search

Ethane exhalation was measured in 42 control subjects, 52 patients with various non-alcoholic liver diseases, and 89 alcohol abusers who had been admitted to hospital for alcohol withdrawal and assessment of liver disease (six with normal liver tests, 10 with steatosis with or without fibrosis, six with alcoholic hepatitis, 29 with cirrhosis, 34 with both cirrhosis and alcoholic hepatitis, and

P Lettéron; V Duchatelle; A Berson; B Fromenty; C Fisch; C Degott; J P Benhamou; D Pessayre

1993-01-01

369

Carotenoids and alcoholic liver disease  

PubMed Central

Chronic and excessive consumption of alcohol leads to the development of alcoholic liver disease. The depletion of vitamin A is a well-known consequence of alcohol consumption, and may be associated with the observed alcohol-induced hepatic injury. The provitamin A carotenoid ?-carotene has been demonstrated to increase alcohol-induced hepatic injury when given in high doses, while low dose supplementation provides protection against hepatic injury. However, it is unknown if the hepatoprotective effects of low dose ?-carotene are due to the protective actions of ?-carotene itself or if the alterations are due to restored vitamin A levels. Future studies are needed to provide further insight into the specific mechanisms by which ?-carotene exerts its protective effect. Further, supplementation studies utilizing high doses of ?-carotene in the presence of alcohol must be done with caution. PMID:24570953

Stice, Camilla P.

2013-01-01

370

Therapy for alcoholic liver disease  

PubMed Central

Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic liver disease (ALD). ALD includes alcoholic steatosis, alcoholic hepatitis, and alcoholic cirrhosis, in order of increasing severity. Important scoring systems of ALD severity include: Child-Pugh, a semi-quantitative scoring system useful to roughly characterize clinical severity; model for end-stage liver disease, a quantitative, objective scoring system used for prognostication and prioritization for liver transplantation; and discriminant function, used to determine whether to administer corticosteroids for alcoholic hepatitis. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including twelve-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Disulfiram decreases alcohol consumption by causing unpleasant sensations after drinking alcohol from accumulation of acetaldehyde in serum, but disulfiram can be hepatotoxic. Adjunctive pharmacotherapies to reduce alcohol consumption include naltrexone, acamprosate, and baclofen. Nutritional therapy helps reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. Although reduced protein intake was previously recommended for advanced ALD to prevent hepatic encephalopathy, a diet containing 1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting. Corticosteroids are first-line therapy for severe alcoholic hepatitis (discriminant function ? 32), but proof of their efficacy in decreasing mortality remains elusive. Pentoxifylline is an alternative therapy. Complications of advanced ALD include ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and portopulmonary hypertension. Alcoholic cirrhotics have increased risk of developing hepatomas. Liver transplantation is the ultimate therapy for severe ALD, but generally requires 6 mo of proven abstinence for eligibility. Alcoholic cirrhotics who maintain abstinence generally have a relatively favorable prognosis after liver transplantation. PMID:24605013

Jaurigue, Maryconi M; Cappell, Mitchell S

2014-01-01

371

Therapy for alcoholic liver disease.  

PubMed

Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic liver disease (ALD). ALD includes alcoholic steatosis, alcoholic hepatitis, and alcoholic cirrhosis, in order of increasing severity. Important scoring systems of ALD severity include: Child-Pugh, a semi-quantitative scoring system useful to roughly characterize clinical severity; model for end-stage liver disease, a quantitative, objective scoring system used for prognostication and prioritization for liver transplantation; and discriminant function, used to determine whether to administer corticosteroids for alcoholic hepatitis. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including twelve-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Disulfiram decreases alcohol consumption by causing unpleasant sensations after drinking alcohol from accumulation of acetaldehyde in serum, but disulfiram can be hepatotoxic. Adjunctive pharmacotherapies to reduce alcohol consumption include naltrexone, acamprosate, and baclofen. Nutritional therapy helps reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. Although reduced protein intake was previously recommended for advanced ALD to prevent hepatic encephalopathy, a diet containing 1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting. Corticosteroids are first-line therapy for severe alcoholic hepatitis (discriminant function ? 32), but proof of their efficacy in decreasing mortality remains elusive. Pentoxifylline is an alternative therapy. Complications of advanced ALD include ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and portopulmonary hypertension. Alcoholic cirrhotics have increased risk of developing hepatomas. Liver transplantation is the ultimate therapy for severe ALD, but generally requires 6 mo of proven abstinence for eligibility. Alcoholic cirrhotics who maintain abstinence generally have a relatively favorable prognosis after liver transplantation. PMID:24605013

Jaurigue, Maryconi M; Cappell, Mitchell S

2014-03-01

372

Entecavir vs lamivudine therapy for naïve patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure  

PubMed Central

AIM: To investigate the short-term and long-term efficacy of entecavir versus lamivudine in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure (ACLF). METHODS: This was a single center, prospective cohort study. Eligible, consecutive hospitalized patients received either entecavir 0.5 mg/d or lamivudine 100 mg/d. All patients were given standard comprehensive internal medicine. The primary endpoint was survival rate at day 60, and secondary endpoints were reduction in hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) levels, and improvement in Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD) scores at day 60 and survival rate at week 52. RESULTS: One hundred and nineteen eligible subjects were recruited from 176 patients with severe acute exacerbation of chronic hepatitis B: 65 were included in the entecavir group and 54 in the lamivudine group (full analysis set). No significant differences were found in patient baseline clinical parameters. At day 60, entecavir did not improve the probability of survival (P = 0.066), despite resulting in faster virological suppression (P < 0.001), higher rates of virological response (P < 0.05) and greater reductions in the CTP and MELD scores (all P < 0.05) than lamivudine. Intriguingly, at week 52, the probability of survival was higher in the entecavir group than in the lamivudine group [42/65 (64.6%) vs 26/54 (48.1%), respectively; P = 0.038]. The pretreatment MELD score (B, 1.357; 95%Cl: 2.138-7.062; P = 0.000) and virological response at day 30 (B, 1.556; 95%Cl: 1.811-12.411; P =0.002), were found to be good predictors for 52-wk survival. CONCLUSION: Entecavir significantly reduced HBV DNA levels, decreased the CTP and MELD scores, and thereby improved the long-term survival rate in patients with spontaneous reactivation of hepatitis B presenting as ACLF. PMID:24782628

Zhang, Yang; Hu, Xiao-Yu; Zhong, Sen; Yang, Fang; Zhou, Tao-You; Chen, Guo; Wang, Yan-Yan; Luo, Jian-Xing

2014-01-01

373

Portal Vein Embolization with Radiolabeled Polyvinyl Alcohol Particles in a Swine Model: Hepatic Distribution and Implications for Pancreatic Islet Cell Transplantation  

SciTech Connect

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.

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

374

[Cholecystolithiasis as a cause of local hepatitis].  

PubMed

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

Dolimov, K S; Il'khamov, F A; Abdumazhidov, A Sh; Tukhtamuradov, Z Z; Dolimov, T K; Pivnitski?, I O

2014-08-01

375

Assessing Women’s Sexual Arousal in the Context of Sexual Assault History and Acute Alcohol Intoxication  

PubMed Central

Introduction Few studies have examined differences in women’s sexual arousal based on sexual assault history (SAH) or in-the-moment alcohol intoxication. Only one has examined combined effects. Findings regarding the relationship between SAH and arousal are contradictory. Aim We aimed to determine the relationship between SAH, alcohol intoxication, and sexual arousal. Main Outcome Measures Genital response was measured by vaginal pulse amplitude (VPA) using vaginal photoplethysmography while watching erotic films. Self-reported sexual arousal was assessed after watching erotic films. Methods Women were randomly assigned to an alcohol (target blood alcohol level = .10%) or control condition and categorized as having a SAH or not. After beverage administration, all women watched erotic films while genital arousal (vaginal pulse amplitude; VPA) was measured. Afterwards self-reported sexual arousal was measured. Results Women with a SAH had smaller increases in genital arousal in response to the films than women without a SAH. Intoxicated women had smaller increases in genital arousal than sober women. However, no differences for SAH or intoxication were found in self-reported arousal. Conclusion SAH and alcohol intoxication are associated with smaller increases in genital arousal compared to women without a SAH and sober women, suggesting that these co-occurring factors impact sexual arousal. PMID:20367775

Gilmore, Amanda K.; Schacht, Rebecca L.; George, William H.; Otto, Jacqueline M.; Davis, Kelly Cue; Heiman, Julia R.; Norris, Jeanette; Kajumulo, Kelly F.

2011-01-01

376

Role of Hypoxia Inducing Factor-1? in Alcohol-Induced Autophagy, Steatosis and Liver Injury in Mice  

PubMed Central

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

Ni, Hong-Min; Bhakta, Amar; Wang, Shaogui; Li, Zhenrui; Manley, Sharon; Huang, Heqing; Copple, Bryan; Ding, Wen-Xing

2014-01-01

377

Silencing of Hepatic Fatty Acid Transporter Protein 5 in Vivo Reverses Diet-induced Non-alcoholic Fatty Liver Disease and  

E-print Network

-alcoholic Fatty Liver Disease and Improves Hyperglycemia*S Received for publication,May 8, 2008, and in revised-alcoholic fatty liver disease is a serious health problem linked to obesity and type 2 diabetes. To investigate fatty acid transport protein 5 in vivo prior to or after establishing non-alcoholic fatty liver disease

Kay, Mark A.

378

Treatment of Alcoholic Liver Disease  

PubMed Central

Alcoholic liver disease (ALD) remains a major cause of morbidity and mortality worldwide. For example, the Veterans Administration Cooperative Studies reported that patients with cirrhosis and superimposed alcoholic hepatitis had a 4-year mortality of >60% (worse than many common cancers such as breast and prostate). The cornerstone for therapy for ALD is lifestyle modification, including drinking cessation and treatment of decompensation, if appropriate. Nutrition intervention has been shown to play a positive role on both an in-patient and out-patient basis. Corticosteroids are effective in selected patients with alcoholic hepatitis, and treatment with pentoxifylline appears to be a promising anti-inflammatory therapy. Recent studies have indicated anti-TNF? therapy, at least for alcoholic hepatitis. Some complementary and alternative medicinal agents, such as milk thistle and S-adenosylmethionine, may be effective in alcoholic cirrhosis. Treatment of the complications of ALD can improve the quality of life and, in some cases, decrease short-term mortality. PMID:16508292

Bergheim, Ina; McClain, Craig J.; Arteel, Gavin E.

2009-01-01

379

sTNFR-II and sICAM-1 are associated with acute disease and hepatic inflammation in schistosomiasis japonica  

Microsoft Academic Search

Soluble intracellular adhesive molecule 1 (sICAM-1) and tumour necrosis factor receptors I (TNFR-1) and II (TNFR-II) have been shown to be associated with numerous liver disorders. Shedding of these membrane proteins can be triggered by the Th1 cytokines, TNF-alpha and IFN-gamma, which are associated with susceptibility or resistance to hepatic schistosomiasis, respectively. Further, TNF-alpha receptors and sICAM-1 have been implicated

Magda K. Ellis; Yuesheng Li; Xunya Hou; Honggen Chen; Donald P. McManus

2008-01-01

380

Moderate acute alcohol intoxication has minimal effect on surround suppression measured with a motion direction discrimination task.  

PubMed

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

Read, Jenny C A; Georgiou, Renos; Brash, Claire; Yazdani, Partow; Whittaker, Roger; Trevelyan, Andrew J; Serrano-Pedraza, Ignacio

2015-01-01

381

Treatment of Alcoholic Liver Disease  

Microsoft Academic Search

Alcoholic liver disease (ALD) remains a major cause of morbidity and mortality worldwide. For example, the Veterans Administration Cooperative Studies reported that patients with cirrhosis and superimposed alcoholic hepatitis had a 4-year mortality of >60% (worse than many common cancers such as breast and prostate). The cornerstone for therapy for ALD is lifestyle modification, including drinking cessation and treatment of

Ina Bergheim; Craig J. McClain; Gavin E. Arteel

2005-01-01