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1

Pharmacotherapy of acute alcoholic hepatitis in clinical practice  

PubMed Central

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

2014-01-01

2

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; Arico, Sarino; Baselice, Aniello; Leone, Silvia; Lozer, Fabiola; Scafato, Emanuele; Borro, Paolo

2014-01-01

3

Alcoholic hepatitis.  

PubMed

Alcoholic hepatitis (AH) is an acute inflammatory syndrome causing significant morbidity and mortality. The prognosis is strongly dependent on disease severity, as assessed by clinical scoring systems. Reliable epidemiological data as well as knowledge of the clinical course of AH are essential for planning and resource allocation within the health care system. Likewise, individual evaluation of risk is desirable in the clinical handling of patients with AH as it can guide treatment, improve patient information, and serve as strata in clinical trials. The present PhD thesis is based on three studies using a cohort of nearly 2000 patients diagnosed with AH in Denmark from 1999 to 2008 as a cohort, in a population-based study design. The aims of this thesis were as follows. (1) To describe the incidence and short- and long-term mortality, of AH in Denmark (Study I). (2) To validate and compare the ability of the currently available prognostic scores to predict mortality in AH (Study II). (3) To investigate the short- and long-term causes of death of patients with AH (Study III). During the study decade, the annual incidence rate in the Danish population rose from 37 to 46 per 106 for men and from 24 to 34 per 106 for women. Both short- and long-term mortality rose for men and women, and the increase in short-term mortality was attributable to increasing patient age and prevalence of cirrhosis. Our evaluation of the most commonly used prognostic scores for predicting the mortality of patients with AH showed that all scores performed similarly, with Area under the Receiver Operator Characteristics curves giving values between 0.74 and 0.78 for 28-day mortality assessed on admission. Our study on causes of death showed that in the short-term (< 84 days after diagnosis), patients with AH were likely to die from liver-related events and infections. In the long-term (? 84 days after diagnosis), those who developed cirrhosis mainly died from liver-related causes, and those who did not develop cirrhosis mainly died from causes related to alcohol abuse. In conclusion, the present thesis provides novel warranted epidemiological information about AH that shows increasing incidence and mortality rates. Consequently, it reiterates the fact that AH is a life-threatening disease and suggests that AH is an increasing public health concern. The most widely used prognostic models may be helpful adjuvants in the routine management of patients with AH, provided that clinicians are aware of the models' limitations. The causes of death in AH are primarily due to liver-related complications, suggesting that patients with AH could benefit from continued follow-up by a hepatologist after the acute episode. PMID:25283626

Sandahl, Thomas Damgaard

2014-10-01

4

Alcohol and Hepatitis C  

MedlinePLUS

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5

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

6

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

7

Pharmacokinetics of ornidazole in patients with acute viral hepatitis, alcoholic cirrhosis, and extrahepatic cholestasis.  

PubMed

Pharmacokinetics of ornidazole, a nitroimidazole derivative, was investigated after intravenous injection in 3 groups of 10 patients with different hepatic diseases: hepatitis, noncholestatic cirrhosis and extrahepatic cholestasis. Plasma concentrations of ornidazole and its two major hydroxylated metabolites, M1 [alpha-(chloromethyl)-2-hydroxymethyl-5-nitroimidazole-1-ethanol] and M4 [3-(2-methyl-5-nitroimidazole 1-yl)-1,2-propane diol] were measured by HPLC assay. As a consequence of a decreased clearance (26% to 48%), the half-life and MRT are increased in all patients by 19% to 38% when compared with healthy volunteers. No clear difference could be established between the different groups. The volume of distribution remains the same in all patients and controls except those suffering from cancer. As previously shown in patients with severe liver cirrhosis, both metabolites accumulate in plasma as a result of decreased elimination; formation is no longer the rate-limiting step of their kinetics. This metabolite accumulation is in part due to decreased biliary excretion and to hepatocellular failure. PMID:2702794

Taburet, A M; Attali, P; Bourget, P; Etienne, J P; Singlas, E

1989-04-01

8

[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

9

Hepatic Cysts: Treatment with Alcohol  

Microsoft Academic Search

Six patients with hepatic cysts were successfully treated with percutaneous aspiration and temporary direct injection of sterile alcohol U.S.P. (95% ethanol) into the cyst cavities through an aspiration catheter. Five cysts were treated percutaneously using sonographic guidance, and one cyst was treated under direct vision during a cholecys- tectom?. It is ideal to treat with 25% replacement volume of alcohol.

William J. Bean; Bruce A. Rodan

10

Alcoholic hepatitis and concomitant hepatitis C virus infection.  

PubMed

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

2014-09-14

11

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

12

Alcohol potentiates hepatitis C virus replicon expression  

Microsoft Academic Search

Alcohol consumption accelerates liver damage and diminishes the anti-hepatitis C virus (HCV) effect of interferon alfa (IFN-?) in patients with HCV infection. It is unknown, however, whether alcohol enhances HCV replication and promotes HCV disease progression. The availability of the HCV replicon containing hepatic cells has provided a unique opportunity to investigate the interaction between alcohol and HCV replicon expression.

Ting Zhang; Yuan Li; Jian-Ping Lai; Steven D. Douglas; David S. Metzger; Charles P. O'Brien; Wen-Zhe Ho

2003-01-01

13

Alcoholic hepatitis: A comprehensive review of pathogenesis and treatment  

PubMed Central

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

2014-01-01

14

Peculiar characteristics of portal-hepatic hemodynamics of alcoholic cirrhosis  

PubMed Central

Alcohol-related cirrhosis is a consequence of heavy and prolonged drinking. Similarly to patients with cirrhosis of other etiologies, patients with alcoholic cirrhosis develop portal hypertension and the hepatic, splanchnic and systemic hemodynamic alterations that follow. However, in alcoholic cirrhosis, some specific features can be observed. Compared to viral cirrhosis, in alcohol-related cirrhosis sinusoidal pressure is generally higher, hepatic venous pressure gradient reflects portal pressure better, the portal flow perfusing the liver is reduced despite an increase in liver weight, the prevalence of reversal portal blood flow is higher, a patent paraumbilical vein is a more common finding and signs of hyperdynamic circulations, such as an increased cardiac output and decreased systemic vascular resistance, are more pronounced. Moreover, alcohol consumption can acutely increase portal pressure and portal-collateral blood flow. Alcoholic cardiomyopathy, another pathological consequence of prolonged alcohol misuse, may contribute to the hemodynamic changes occurring in alcohol-related cirrhosis. The aim of this review was to assess the portal-hepatic changes that occur in alcohol-related cirrhosis, focusing on the differences observed in comparison with patients with viral cirrhosis. The knowledge of the specific characteristics of this pathological condition can be helpful in the management of portal hypertension and its complications in patients with alcohol-related cirrhosis. PMID:25009370

Bolognesi, Massimo; Verardo, Alberto; Di Pascoli, Marco

2014-01-01

15

Serological diagnosis of acute viral hepatitis  

Microsoft Academic Search

Fifty cases of symptomatic acute viral hepatitis presenting at the Washington, D.C., Veterans Administration Medical Center between 1976 and 1977 were tested for serological markers of hepatitis virus infection. The etiology of the acute hepatitis appeared to be hepatitis A virus in 20%, hepatitis B virus in 52%, non-A, non-B agents in 22%, delta hepatitis in 4%, and infectious mononucleosis

Jay H. Hoofnagle; Antonio Ponzetto; Lars R. Mathiesen; Jeanne G. Waggoner; Z. Buskell Bales; Leonard B. Seeff

1985-01-01

16

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.

Kim, Won; Kim, Dong Joon

2014-01-01

17

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

18

Hepatitis B vaccination in chronic alcoholics.  

PubMed

Given the possible role of hepatitis B virus in the occurrence of hepatocellular carcinoma and the high prevalence of HBV infection in alcoholics, we attempted to prevent HBV infection in alcoholic patients with or without cirrhosis. Among 32 cirrhosis, 20 received three injections of hepatitis B vaccine at monthly intervals and 12 had a 4th injection one month later. Effectiveness was evaluated on the anti-HBs titer at the 6th month; it did not differ between the 3- and 4-injection groups. Two patients were good responders (anti-HBs greater than 300 mU/ml), 14 had a low response (m-30 mU/ml at the peak) and 16 (50%) had no detectable anti-HBs. All alcoholics without cirrhosis were given 4 injections; all had detectable anti-HBs but their mean antibody response was 97.7 +/- 4 SD. No obvious statistical difference in the response to the vaccine was noted on the basis of sex or age, or on the discontinuation or not of alcohol intake. Deficient antibody response to vaccines has not previously been demonstrated in patients with cirrhosis or in alcoholics. It remains to be determined whether this response is specific of HBV and how it could be related to the role of HBV in the occurrence of liver alterations in alcoholics. PMID:2941477

Degos, F; Duhamel, G; Brechot, C; Nalpas, B; Courouce, A M; Tron, F; Berthelot, P

1986-01-01

19

Acute Hepatitis C: A Systematic Review  

Microsoft Academic Search

INTRODUCTION:The annual incidence of acute hepatitis C virus (HCV) has fallen in recent years, primarily because of effective blood screening efforts and increased education on the dangers of needle sharing. However, hepatitis C infection is still relatively frequent in certain populations. Most patients infected with HCV are unaware of their exposure and remain asymptomatic during the initial stages of the

Sanaa M. Kamal

2008-01-01

20

Is liver biopsy necessary in the management of alcoholic hepatitis?  

PubMed

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

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

2013-11-28

21

Current concepts and controversies in the treatment of alcoholic hepatitis.  

PubMed

The treatment of alcoholic hepatitis remains one of the most debated topics in medicine and a field of continued research. In this review, we discuss the evolution of scoring systems, including the recent development of the Glasgow alcoholic hepatitis score, role of liver biopsy and current treatment interventions. Studies of treatment interventions with glucocorticoids, pentoxifylline, infliximab, s-adenosyl-methionine, and colchicine are reviewed with discussion on quality. Glucocorticoids currently remain the mainstay of treatment for severe alcoholic hepatitis. PMID:17109510

Rongey, Catherine; Kaplowitz, Neil

2006-11-21

22

Acute alcohol intoxication and female orgasmic response  

Microsoft Academic Search

This study tested the hypothesis that increasing levels of acute alcohol intoxication are related to systematic changes in female orgasmic experience reflected by physiological, behavioral, and cognitive indices. Using a repeated measures design with monthly experimental sessions, each of 18 university women were sustained at four different blood alcohol concentrations (BAC) in counterbalanced order prior to viewing sexually explicit videotapes

Victor J. Malatesta; Robert H. Pollack; Terri D. Crotty; Lelon J. Peacock

1982-01-01

23

[Aplastic anemia after acute viral hepatitis].  

PubMed

The authors describe 4 patients with grave aplastic anemia that developed after acute virus hepatitis. In two cases aplasia occurred at the icteric period of hepatitis, in one during convalescence, and in one 5 months after the recovery from hepatitis. The counter electrophoresis technique failed to reveal the Australian antigen in all the 4 cases. Ninety per cent of patients out of over 200 reported cases of aplastic anemia that developed after acute virus hepatitis died. Of the 4 cases followed up by the authors, 3 patients died. One of the female patients was subjected to splenectomy 3 weeks after the occurrence of grave aplasia with fatty bone marrow with a purpose of immunodepression. Splenectomy entailed a considerable decrease in hemorrhagic diathesis. Later on the patient was treated with caprine antilymphocytic globulin. At present the patient is in a state of remission. The problems of the pathogenesis of aplastic anemia following acute virus hepatitis and potentialities of the disease treatment are under discussion. PMID:4049269

Idel'son, L I; Guse?nova, L A; Pogorel'skaia, E P; Aprosina, Z G; Novokreshchennykh, I I

1985-01-01

24

Blood culture-positive infections in patients with alcoholic hepatitis.  

PubMed

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

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

2014-12-01

25

Hepatitis mouse models: from acute-to-chronic autoimmune hepatitis.  

PubMed

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease associated with interface hepatitis, raised plasma liver enzymes, the presence of autoantibodies and regulatory T-cell (Tregs) dysfunction. The clinical course is heterogeneous, manifested by a fulminant or indolent course. Although genetic predisposition is well accepted, the combination with currently undefined environmental factors is crucial for the development of the disease. Progress in the development of reliable animal models provides added understanding of the pathophysiology of AIH, and these will be very useful in evaluating potential therapeutics. It appears that artificially breaking tolerance in the liver is easy. However, maintaining this state of tolerance breakdown, to get chronic hepatitis, is difficult because liver immune homeostasis is strongly regulated by several immune response inhibitory mechanisms. For example, Tregs are crucial regulators in acute and chronic hepatitis, and C57BL/6 mice are most prone to experimental AIH. Immunization of C57BL/6 mice with liver (AIH) autoantigens (CYP2D6/FTCD or IL-4R) and the disturbance of liver regulatory mechanism(s), leading to experimental AIH, are likely to be most representative of human AIH pathology. PMID:25112417

Yüksel, Muhammed; Laukens, Debby; Heindryckx, Femke; Van Vlierberghe, Hans; Geerts, Anja; Wong, F Susan; Wen, Li; Colle, Isabelle

2014-10-01

26

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

27

Hepatic Growth Hormone Resistance After Acute Injury  

PubMed Central

Severe injury and infection are often followed by accelerated protein catabolism and acute insulin resistance. This results in several effects that complicate and prolong recovery, including weakness, immobility, impaired wound healing, and organ dysfunction. Recent studies have demonstrated the development of GH resistance during severe inflammation, providing a potential mechanism for the protein loss that follows injury and infection. To understand this GH resistance, we recently developed a murine model of acute injury. Mice were subjected to soft-tissue injury, alone or combined with hemorrhage, and injected iv with GH 30, 60, or 90 minutes later. Hepatic GH signaling was measured via Western analysis. GH-induced signal transducer and activator of transcription 5 phosphorylation was decreased immediately after completion of the trauma procedure, and at 30 and 60 minutes, but further decreased by 90 minutes after trauma. Combined trauma and hemorrhage resulted in severely decreased GH-induced signal transducer and activator of transcription 5 phosphorylation compared with trauma alone, and this was true at all time points studied. Western analysis revealed an apparent decrease in the molecular weight of the hepatic GH receptor (GHR) after trauma and hemorrhage, but not trauma alone. Additional studies determined that the hemorrhage-induced decrease in receptor size was not due to changes in GHR N-linked glycosylation. These results suggest that GH sensitivity is rapidly impaired after acute injury and that trauma combined with hemorrhage results in a more severe form of GH resistance resulting from alteration or inactivation of hepatic GHR. PMID:23417424

Corrick, Ryan M.; Li, Li; Frank, Stuart J.

2013-01-01

28

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

29

Interactions between alcohol and hepatitis viruses in the liver.  

PubMed

There is a high frequency of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among individuals with alcoholic liver disease (ALD) and alcohol-associated hepatocellular carcinoma (HCC), suggesting that these viruses are implicated in the pathogenesis of these diseases. Alcohol may act synergistically by promoting the development and progression of liver disease. The interactions of alcohol with infected hepatocytes and with antiviral immunity may result in altered patterns of virus gene expression and replication, making diagnosis difficult in some cases of ALD and HCC. The potential association of ALD and alcoholic HCC with serologically negative virus variants raises major difficulties in the epidemiologic assessment of cause and effect, providing major challenges for the future. PMID:8792072

Brechot, C; Nalpas, B; Feitelson, M A

1996-06-01

30

Clinical application of hepatitis C virus core protein in early diagnosis of acute hepatitis C  

Microsoft Academic Search

:   A fluorescence enzyme immunoassay (FEIA) for the quantitative measurement of hepatitis C virus (HCV) core protein has recently\\u000a been developed. In this study, we studied the clinical usefulness of this measurement in patients with acute hepatitis C.\\u000a Eighteen patients with post-transfusion acute hepatitis C were enrolled in the study; 5 patients showed resolution of hepatitis\\u000a with disappearance of HCV

Masakazu Kobayashi; Eiji Tanaka; Akihiro Matsumoto; Kaname Yoshizawa; Haruhiko Imai; Takeshi Sodeyama; Kendo Kiyosawa

1998-01-01

31

Liver transplantation for acute hepatic failure  

PubMed Central

There are numerous causes of acute hepatic failure (AHF). Cerebral edema, coagulopathy, renal failure, metabolic disturbances and infection are the main clinical sequelae. Patients with AHF should be stabilized when first encountered and transferred to the nearest liver transplant center, as AHF progresses quickly and is often fatal. There are few adequate medical interventions and care of patients with AHF is supportive until spontaneous recovery ensues. If recovery does not appear to occur, most causes of AHF are well accepted indications for liver transplantation. PMID:18333235

Castaldo, Eric T.

2006-01-01

32

Bermuda Triangle for the liver: alcohol, obesity, and viral hepatitis.  

PubMed

Despite major progress in understanding and managing liver disease in the past 30 years, it is now among the top 10 most common causes of death globally. Several risk factors, such as genetics, diabetes, obesity, excessive alcohol consumption, viral infection, gender, immune dysfunction, and medications, acting individually or in concert, are known to precipitate liver damage. Viral hepatitis, excessive alcohol consumption, and obesity are the major factors causing liver injury. Estimated numbers of hepatitis B virus (HBV) and hepatitis C virus (HCV)-infected subjects worldwide are staggering (370 and 175 million, respectively), and of the 40 million known human immunodeficiency virus positive subjects, 4 and 5 million are coinfected with HBV and HCV, respectively. Alcohol and HCV are the leading causes of end-stage liver disease worldwide and the most common indication for liver transplantation in the United States and Europe. In addition, the global obesity epidemic that affects up to 40 million Americans, and 396 million worldwide, is accompanied by an alarming incidence of end-stage liver disease, a condition exacerbated by alcohol. This article focuses on the interactions between alcohol, viral hepatitis, and obesity (euphemistically described here as the Bermuda Triangle of liver disease), and discusses common mechanisms and synergy. PMID:23855291

Zakhari, Samir

2013-08-01

33

Hepatitis B and C markers among alcoholics in Israel: High incidence of HCV infection  

Microsoft Academic Search

Patients with alcoholic liver disease have an increased prevalence of viral hepatitis. However, the role of demographic characteristics has not been adequately delineated. Therefore, we examined and compared the seroprevalences of hepatitis B and C in Israeli alcoholic patients to that of blood donors control group by their country of birth and origin. Hepatitis B surface antigen, hepatitis B core

Isaac Srugo; Eilat Shinar; Shulamit Bar-Shany; Lanir Amos

1998-01-01

34

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

35

Hepatitis C viremia and anti-HCV antibodies in alcoholics.  

PubMed

We determined serum hepatitis C status using a RIBA2 kit and a sensitive PCR procedure in 62 chronic alcoholics, 36 of whom had anti-HCV antibodies (Ab) detectable in an ELISA1 assay. Anti-HCV antibodies were detected in 22 patients using RIBA2. HCV RNA was detected by means of PCR in 18 patients who were RIBA2 positive and in none who were RIBA2 negative. Liver biopsies, available for 12 HCV RNA-positive patients, revealed histological features of purely alcohol-related lesions in seven and mixed alcohol-viral lesions in five. These results indicate that HCV replication is maintained in most alcoholics who score positive for anti-HCV Ab in the RIBA2 test, and that HCV viremia can be associated with histological features typical of alcoholic liver disease. PMID:1380027

Nalpas, B; Thiers, V; Pol, S; Driss, F; Thepot, V; Berthelot, P; Brechot, C

1992-03-01

36

Effect of allyl alcohol-induced sublethal hepatic damage upon doxorubicin metabolism and toxicity in the rabbit.  

PubMed

A model of hepatic dysfunction in vivo has been developed in rabbits to determine the effects of sublethal hepatocellular necrosis upon doxorubicin pharmacology. Eight New Zealand white rabbits were given 3 mg/kg doxorubicin i.v. Plasma doxorubicin and metabolite pharmacokinetics were determined and toxicity assessed by nadir complete blood counts. Hepatic function was assessed by the pulmonary excretion rate of 14CO2 from [14C]aminopyrine. Hepatocellular necrosis was produced by i.v. injection of 1.35 mg/kg of a 2% allyl alcohol solution. Doxorubicin administration and pharmacokinetics were repeated. Doxorubicin enhances the hepatotoxicity of allyl alcohol. Hepatocellular necrosis does not alter the plasma pharmacokinetics of doxorubicin but does increase the plasma exposure of doxorubicinol. Doxorubicin-induced myelosuppression is enhanced by allyl alcohol pretreatment. These data suggest that in circumstances of reduced hepatocellular volume or acute hepatocellular necrosis, a key plasma marker of doxorubicin-induced acute toxicity may be doxorubicinol. PMID:3581067

Brenner, D E; Anthony, L B; Halter, S; Harris, N L; Collins, J C; Hande, K R

1987-06-15

37

Alcohol induced hepatic fibrosis: Role of acetaldehyde  

Microsoft Academic Search

Alcohol abuse is one of the major causes of liver fibrosis worldwide. Although the pathogenesis of liver fibrosis is a very complex phenomenon involving different molecular and biological mechanisms, several lines of evidence established that the first ethanol metabolite, acetaldehyde, plays a key role in the onset and maintenance of the fibrogenetic process. This review briefly summarizes the molecular mechanisms

Tommaso Mello; Elisabetta Ceni; Calogero Surrenti; Andrea Galli

2008-01-01

38

Motor performance during and following acute alcohol intoxication in healthy non-alcoholic subjects  

Microsoft Academic Search

Chronic alcohol abuse has adverse effects on skeletal muscle, and reduced muscle strength is frequently seen in chronic alcoholics.\\u000a In this study the acute effects of moderate alcohol intoxication on motor performance was evaluated in 19 non-alcoholic healthy\\u000a subjects (10 women, 9 men). A randomised double-blinded placebo controlled design was applied to subjects receiving alcohol\\u000a in juice and pure juice

M. B. Poulsen; J. Jakobsen; N. K. Aagaard; H. Andersen

2007-01-01

39

Severe Thrombocytopenia Associated with Acute Hepatitis E Virus Infection ?  

PubMed Central

We describe here what is, to the best of our knowledge, the third reported case of severe thrombocytopenia associated with acute hepatitis E virus infection. The patient was a 72-year-old French woman. It seems likely that the cause of the thrombocytopenia was acute hepatitis E virus infection, possibly occurring via an immune mechanism. No complications were noted, in contrast to the two previous reports. PMID:18480231

Colson, P.; Payraudeau, E.; Leonnet, C.; De Montigny, S.; Villeneuve, L.; Motte, A.; Tamalet, C.

2008-01-01

40

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

PubMed Central

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

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

2014-01-01

41

Inhibitory Effects of Pretreatment with Radon on Acute Alcohol-Induced Hepatopathy in Mice  

PubMed Central

We previously reported that radon inhalation activates antioxidative functions in the liver and inhibits carbon tetrachloride-induced hepatopathy in mice. In addition, it has been reported that reactive oxygen species contribute to alcohol-induced hepatopathy. In this study, we examined the inhibitory effects of radon inhalation on acute alcohol-induced hepatopathy in mice. C57BL/6J mice were subjected to intraperitoneal injection of 50% alcohol (5?g/kg bodyweight) after inhaling approximately 4000?Bq/m3 radon for 24?h. Alcohol administration significantly increased the activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) in serum, and the levels of triglyceride and lipid peroxide in the liver, suggesting acute alcohol-induced hepatopathy. Radon inhalation activated antioxidative functions in the liver. Furthermore, pretreatment with radon inhibited the depression of hepatic functions and antioxidative functions. These findings suggested that radon inhalation activated antioxidative functions in the liver and inhibited acute alcohol-induced hepatopathy in mice. PMID:23213269

Toyota, Teruaki; Kataoka, Takahiro; Nishiyama, Yuichi; Taguchi, Takehito; Yamaoka, Kiyonori

2012-01-01

42

Plasma and urine biomarkers in acute viral hepatitis E  

PubMed Central

Background Hepatitis E, caused by the hepatitis E virus (HEV), is endemic to developing countries where it manifests as waterborne outbreaks and sporadic cases. Though generally self-limited with a low mortality rate, some cases progress to fulminant hepatic failure (FHF) with high mortality. With no identified predictive or diagnostic markers, the events leading to disease exacerbation are not known. Our aim is to use proteomic tools to identify biomarkers of acute and fulminant hepatitis E. Results We analyzed proteins in the plasma and urine of hepatitis E patients and healthy controls by two-dimensional Differential Imaging Gel Electrophoresis (DIGE) and mass spectrometry, and identified over 30 proteins to be differentially expressed during acute hepatitis E. The levels of one plasma protein, transthyretin, and one urine protein, alpha-1-microglobulin (?1m), were then quantitated by enzyme immunoassay (EIA) in clinical samples from a larger group of patients and controls. The results showed decreased plasma transthyretin levels (p < 0.005) and increased urine ?1m levels (p < 0.001) in acute hepatitis E patients, compared to healthy controls. Preliminary results also showed lower urine zinc alpha glycoprotein levels in fulminant hepatitis E compared to acute disease; this remains to be confirmed with more fulminant cases. Conclusion Our results demonstrate the utility of characterizing plasma and urine proteomes for signatures of the host response to HEV infection. We predict that plasma transthyretin and urine ?1m could be reliable biomarkers of acute hepatitis E. Besides the utility of this approach to biomarker discovery, proteome-level changes in human biofluids would also guide towards a better understanding of host-virus interaction and disease. PMID:19860894

Taneja, Shikha; Sen, Somdutta; Gupta, Vijay K; Aggarwal, Rakesh; Jameel, Shahid

2009-01-01

43

Preparing to approach or avoid alcohol: EEG correlates, and acute alcohol effects.  

PubMed

Recently an approach-bias for alcohol has been described as an important cognitive motivational process in the etiology of alcohol use problems. In the approach-bias, perception and action are inextricably linked and stimulus response associations are central to this bias: performance improves when task instructions are congruent with a pre-existing stimulus-response association. These pre-existing response associations could potentially allow advance response preparation and execution. The present study aimed at investigating the effect of the alcohol approach bias on response preparation by means of event-related desynchronization in the beta band (beta-ERD) of the EEG signal and the effect of acute alcohol in the approach bias in response to alcohol cues. Subjects (18 social drinkers) performed an adapted alcohol-Approach Avoidance Task, in which a preparatory period was provided between alcohol/soft drink cues and approach/avoid responses. Subjects were tested both in a placebo and in an alcohol condition (counterbalanced). Posterior beta-ERD was found to increase during preparation for alcohol-approach trials. The beta-ERD in the congruent block increased following alcohol administration. These results suggest that advance response preparation may play a role in the alcohol approach bias and that acute alcohol facilitates response preparatory processes for approach alcohol trials. Future EEG studies using the adapted AAT may help understanding approach biases in addiction. PMID:24334167

Korucuoglu, Ozlem; Gladwin, Thomas E; Wiers, Reinout W

2014-01-24

44

Injections given in healthcare settings as a major source of acute hepatitis B in Moldova  

Microsoft Academic Search

Background Reported rates of acute hepatitis B are high in many former Soviet Union republics and modes of transmission are not well defined. Methods Two case-control studies were undertaken in Moldova to identify risk factors for acute hepatitis B in people aged 2-15 years (children) and >15 years (adults). Serologically confirmed acute hepatitis B cases occurring between 1 January 1994

Yvan JF; Rafael Harpaz; Jan Drobeniuc; Anatol Melnic; Michael Favorov; Petru Iarovoi; Craig N Shapiroa; Bradley A Woodruff

1999-01-01

45

Distinct cellular responses differentiating alcohol- and hepatitis C virus-induced liver cirrhosis  

Microsoft Academic Search

BACKGROUND: Little is known at the molecular level concerning the differences and\\/or similarities between alcohol and hepatitis C virus induced liver disease. Global transcriptional profiling using oligonucleotide microarrays was therefore performed on liver biopsies from patients with cirrhosis caused by either chronic alcohol consumption or chronic hepatitis C virus (HCV). RESULTS: Global gene expression patterns varied significantly depending upon etiology

Sharon L Lederer; Kathie-Anne Walters; Sean Proll; Bryan Paeper; Shahar Robinzon; Loreto Boix; Nelson Fausto; Jordi Bruix; Michael G Katze

2006-01-01

46

Acute Acalculous Cholecystitis due to Viral Hepatitis A  

PubMed Central

Inflammation of the gallbladder without evidence of calculi is known as acute acalculous cholecystitis (AAC). AAC is frequently associated with gangrene, perforation, and empyema. Due to these associated complications, AAC can be associated with high morbidity and mortality. Medical or surgical treatments can be chosen according to the general condition of the patient, underlying disease and agent. Particularly in acute acalculous cholecystitis cases, early diagnosis and early medical treatment have a positive effect on the patient and protect them from surgical trauma. ACC is a rare complication of acute viral hepatitis A. Herein, we present an adult patient of acalculous cholecystitis due to acute viral hepatitis A. She responded to the conservative management. PMID:24106622

Kaya, Safak; Ay, Nurettin; Baysal, Birol; Bahadir, Mehmet Veysi; Onur, Arzu; Duymus, Recai

2013-01-01

47

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

Microsoft Academic Search

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

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

2002-01-01

48

Acute viral hepatitis morbidity and mortality associated with hepatitis E virus infection: Uzbekistan surveillance data  

Microsoft Academic Search

BACKGROUND: In Uzbekistan, routine serologic testing has not been available to differentiate etiologies of acute viral hepatitis (AVH). To determine the age groups most affected by hepatitis E virus (HEV) during documented AVH epidemics, trends in AVH-associated mortality rate (MR) per 100,000 over a 15-year period and reported incidence of AVH over a 35-year period were examined. METHODS: Reported AVH

Makhmudkhan B Sharapov; Michael O Favorov; Tatiana L Yashina; Matthew S Brown; Gennady G Onischenko; Harold S Margolis; Terence L Chorba

2009-01-01

49

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

PubMed

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

2014-09-14

50

Acute Ethanol Causes Hepatic Mitochondrial Depolarization in Mice: Role of Ethanol Metabolism  

PubMed Central

Background/Aims An increase of ethanol metabolism and hepatic mitochondrial respiration occurs in vivo after a single binge of alcohol. Here, our aim was to determine how ethanol intake affects hepatic mitochondrial polarization status in vivo in relation to ethanol metabolism and steatosis. Methods Hepatic mitochondrial polarization, permeability transition (MPT), and reduce pyridine nucleotides, and steatosis in mice were monitored by intravital confocal/multiphoton microscopy of the fluorescence of rhodamine 123 (Rh123), calcein, NAD(P)H, and BODIPY493/503, respectively, after gavage with ethanol (1–6 g/kg). Results Mitochondria depolarized in an all-or-nothing fashion in individual hepatocytes as early as 1 h after alcohol. Depolarization was dose- and time-dependent, peaked after 6 to 12 h and maximally affected 94% of hepatocytes. This mitochondrial depolarization was not due to onset of the MPT. After 24 h, mitochondria of most hepatocytes recovered normal polarization and were indistinguishable from untreated after 7 days. Cell death monitored by propidium iodide staining, histology and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was low throughout. After alcohol, mitochondrial NAD(P)H autofluorescence increased and decreased, respectively, in hepatocytes with polarized and depolarized mitochondria. Ethanol also caused steatosis mainly in hepatocytes with depolarized mitochondria. Depolarization was linked to ethanol metabolism, since deficiency of alcohol dehydrogenase and cytochrome-P450 2E1 (CYP2E1), the major ethanol-metabolizing enzymes, decreased mitochondrial depolarization by ?70% and ?20%, respectively. Activation of aldehyde dehydrogenase decreased depolarization, whereas inhibition of aldehyde dehydrogenase enhanced depolarization. Activation of aldehyde dehydrogenase also markedly decreased steatosis. Conclusions Acute ethanol causes reversible hepatic mitochondrial depolarization in vivo that may contribute to steatosis and increased mitochondrial respiration. Onset of this mitochondrial depolarization is linked, at least in part, to metabolism of ethanol to acetaldehyde. PMID:24618581

Zhong, Zhi; Ramshesh, Venkat K.; Rehman, Hasibur; Liu, Qinlong; Theruvath, Tom P.; Krishnasamy, Yasodha; Lemasters, John J.

2014-01-01

51

Acute hepatitis C infection with unclear route of transmission.  

PubMed

A 43-year old man acquired acute hepatitis C virus (HCV) infection with unclear route of transmission. There were no known sexual or other risk factors for HCV acquisition. Phylogenetic analysis confirmed that the case was infected with identical genotype 1b strain. After symptomatic treatment for three weeks, the HCV was spontaneously cleared and liver function recovered. PMID:23155971

Cheng, J; Jiang, S W; Zhang, L Z; Zhou, Z S; Li, J B; Li, X; Sun, Q L

2012-03-01

52

Secondary immune response to hepatitis B virus vaccine in alcoholics.  

PubMed

The efficacy of full vaccination against hepatitis B virus (i.e., including the 1-year booster injection) was evaluated in 28 alcoholic patients with minimal liver disease. Although such patients are reportedly poor responders, the proportion of those protected (anti-HBs titer > = 10 mlU/ml) rose from 42.8% after primary immunization to 82% after the booster. The mean anti-HBs titer, which remained low in the overall group, was significantly lower in the subjects who resumed drinking during the follow-up period than in those who did not. This suggests a direct influence of alcohol itself on the response, because none of our patients had cirrhosis and none were clearly malnourished. Among the 17 patients for whom the 2-year post-booster anti-HBs titer could be determined, all those with a 1-month postbooster titer above 1000 mlU/ml still had a high anti-HBs level (> 100), whereas 80% of those with a 1-month postbooster titer < 1000 had 2 years later only a low (< 100) or even an unprotective anti-HBs level; this means that only the latter should be considered for a new booster injection. Our data indicate that protection against hepatitis B virus can be achieved in a good proportion of alcoholics with a full vaccination protocol. We suggest that efficacy should be evaluated 1 month after the booster, and that patients with low postbooster anti-HBs titers should be tested at regular intervals, because they can also be protected provided an adapted schedule of further injections is conducted. PMID:8488971

Nalpas, B; Thepot, V; Driss, F; Pol, S; Courouce, A M; Saliou, P; Berthelot, P

1993-04-01

53

Understanding the presence of false-positive antibodies in acute hepatitis.  

PubMed

Although false-positive antibodies (FPAs) have been well described in chronic hepatitis C virus (HCV), this has not been evaluated in acute viral hepatitis. Patients with acute viral hepatitis underwent antibody testing for other causes of liver disease and sexually transmitted diseases. Those with antibody positivity underwent confirmatory testing and monitoring. Patients with FPAs were compared with patients with acute hepatitis C infection without FPAs. In total 7 of 24 patients (29%) had FPAs. FPAs during acute viral hepatitis are associated with higher IgM levels and higher ESR in acute HCV. This has both mechanistic and clinical implications and should be evaluated further. PMID:24943727

Sakiani, Sasan; Koh, Christopher; Heller, Theo

2014-12-15

54

Steatosis of granular pneumocytes in alcoholics with acute alveolar injury.  

PubMed

Accumulation of neutral lipid in the type II alveolar epithelial cells of the lung has been described in experiments involving animals with conditions such as hypoxia or on alcohol administration. In two cases involving human subjects, this change was observed at autopsy by histochemical stains and electron microscopy. In both instances, the patients had had severe alcoholic liver disease, as well as extreme hypoxia resulting from acute alveolar injury. The lungs of six alcoholic patients with liver disease but without acute alveolar injury showed no lipid vesicles on histochemical staining. These observations suggest that a metabolic insult or combination of insults, such as alcohol or hypoxia, might lead to accumulation of neutral lipid, especially in regenerating alveolar epithelial cells that may be more susceptible to such injury. PMID:582366

Sridhar, S R; Ryan, S F

1979-09-01

55

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

PubMed Central

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 minorRE 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.

2013-01-01

56

Alcohol abuse-related severe acute pancreatitis with rhabdomyolysis complications.  

PubMed

Non-traumatic rhabdomyolysis is a rare complication of acute pancreatitis. One of the major risk factors of both acute pancreatitis and rhabdomyolysis is alcohol abuse. However, only a few studies have reported the prognosis and association of severe acute pancreatitis (SAP) and rhabdomyolysis in alcohol abuse patients. In the present study, we report two cases presenting with SAP complicated by rhabdomyolysis following high-dose alcohol intake. The disease onset, clinical manifestations, laboratory data, diagnosis and treatment procedure of each patient were recorded, and the association with rhabdomyolysis was analyzed. Alcohol consumption was the most predominant cause of SAP and rhabdomyolysis in these patients. SAP-related rhabdomyolysis was primarily induced by the toxicity associated with pancreatic necrosis. The laboratory tests revealed that the concentration of serum creatine kinase (CK) and myoglobin increased and acute renal failure symptoms were present, which provided an exact diagnosis for SAP-induced rhabdomyolysis. Rhabdomyolysis and subsequent hypermyoglobinuria severely impaired kidney function and aggravated hypocalcemia. The therapy of early stage SAP complicated by rhabdomyolysis involved liquid resuscitation support. When first stage treatment fails, blood purification should be performed immediately. Both patients developed multiple organ failure (MOF) and succumbed to the disease. Considering the two cases presented, we conclude that alcohol-related SAP complicated by rhabdomyolysis may have a poor clinical prognosis. PMID:23251265

Su, Mao-Sheng; Jiang, Ying; Yan, Xiao-Yuan Hu; Zhao, Qing-Hua; Liu, Zhi-Wei; Zhang, Wen-Zhi; He, Lei

2013-01-01

57

The Amount of Alcohol Consumption Negatively Impacts Short-Term Mortality in Mexican Patients With Alcoholic Hepatitis  

Microsoft Academic Search

OBJECTIVES:Mexicans have an increased rate of alcohol abuse and alcoholic liver disease. Factors influencing the severity of alcoholic hepatitis (AH) in Mexicans are unknown. The aims of the present study were to identify the prognostic factors of short-term mortality in Mexican patients with AH and to validate the existing prognostic models.METHODS:One hundred seventy-five consecutive patients with AH were recruited from

José Altamirano; Fátima Higuera-de laTijera; Andres Duarte-Rojo; Manuel A Martínez-Vázquez; Juan G Abraldes; Luis Enrique Herrera-Jiménez; Javier Michelena; Laura Zapata; José Perez-Hernández; Aldo Torre; José A Gonzáles-González; Andres Cardenas; Marlene Dominguez; Vicente Arroyo; Pere Ginès; Juan Caballería; Ramón Bataller

2011-01-01

58

Significance of intravascular coagulation and fibrinolysis in acute hepatic failure  

PubMed Central

Twenty-two patients with acute hepatic failure were studied to determine the incidence and magnitude of intravascular coagulation and fibrinolysis and their relation to the severity of bleeding and prognosis. The mean platelet count, Thrombotest, plasminogen activator, and plasminogen were reduced; the reduction in fibrinogen was not statistically significant. Fibrin/fibrinogen degradation products were only moderately increased. Hepatic fibrin deposition was not extensive, being present in 11 of 22 hepatic sections, more in areas of confluent necrosis than in the sinusoids. The combination of increased fibrin/fibrinogen degradation products with decreased plasminogen activator, plasminogen, and thrombocytopenia is consistent with a diagnosis of intravascular coagulation and secondary local fibrinolysis. However, neither of these processes was severe. Severity of bleeding was related only to plasminogen levels and prognosis only to Thrombotest levels. There was no relation between hepatic histological and haematological findings. Heparin therapy is not indicated in the routine management of acute hepatic failure, as intravascular coagulation is not severe and heparin may itself cause massive bleeding. ImagesFig 5 PMID:4820641

Hillenbrand, P.; Parbhoo, S. P.; Jedrychowski, A.; Sherlock, Sheila

1974-01-01

59

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.

60

Acute effects of alcohol on the development of intrusive memories  

Microsoft Academic Search

Rationale  Post-traumatic stress disorder is characterised by repeated intrusive imagery of the traumatic event. Despite alcohol's impairing\\u000a effect on memory and frequent involvement in real-life trauma, virtually nothing is known of the interaction between alcohol\\u000a and trauma memory.\\u000a \\u000a \\u000a \\u000a Objective  We aimed to investigate the acute alcohol effects on spontaneous memories following a trauma film as well as explicit memory\\u000a for the film.

James A. Bisby; Chris R. Brewin; Julie R. Leitz; H. Valerie Curran

2009-01-01

61

Protective effects of maslinic acid against alcohol-induced acute liver injury in mice.  

PubMed

Protective effects of maslinic acid (MA) at 10, 15 or 20?mg/kg body weight/day against alcohol-induced acute hepatotoxicity in mice were examined. Mice were administrated by MA for 3 weeks, and followed by alcohol treatment. Results showed that MA pre-intake at three doses resulted in its accumulation in the liver; and dose-dependently lowered cytochrome P450 2E1 activity and protein expression at 23.5-51.2% and 21.4-62.3%, respectively (P?<0.05). MA pre-intake decreased subsequent alcohol-induced reactive oxygen species, interleukin-6, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, nitric oxide and prostaglandin E2 production; retained glutathione content; maintained catalase and glutathione peroxidase activities; and declined cyclooxygenase-2 and total nitric oxide synthase activities in the liver (P?<0.05). Furthermore, MA pre-intake suppressed 17.3-51.7% nuclear factor kappa (NF-?)B p50, 23.5-58.8% NF-?B p65, 25.6-62.4% p-p38 and 24.1-63.0% p-JNK expression in the liver (P?<0.05). Histological data indicated that MA intake at test doses attenuated hepatic inflammatory infiltrate. These findings support that maslinic acid is a potent preventive agent against acute alcoholic liver disease. PMID:25301236

Yan, Sheng-Lei; Yang, Hui-Ting; Lee, Hsiang-Lin; Yin, Mei-Chin

2014-12-01

62

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

E-print Network

1 MATERNAL COFFEE AND ALCOHOL CONSUMPTION DURING PREGNANCY, PARENTAL SMOKING AND RISK OF CHILDHOOH ACUTE LEUKEMIA Short title: Maternal coffee and alcohol consumption, parental smoking and childhood frequency matched controls. The results suggest an association between maternal alcohol and coffee

Paris-Sud XI, Université de

63

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

PubMed Central

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

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

2011-01-01

64

Acute hepatitis B after autologous stem cell transplantation in a man previously infected by hepatitis B virus  

Microsoft Academic Search

We report a case of acute hepatitis B after autologous stem cell transplantation (ASCT) in a patient with low-grade non-Hodgkin’s lymphoma. At diagnosis of the hematological disease, the patient had the characteristic serology of a previous hepatitis B infection, being Ag HBs negative, hepatitis B virus core antibody positive (anti-HBC) and hepatitis B virus surface antibody weakly positive. He developed

D Senecal; E Pichon; F Dubois; M Delain; C Linassier; Ph Colombat

1999-01-01

65

Influence of chronic HBV infection on superimposed acute hepatitis E  

PubMed Central

AIM: To investigate the influence of chronic hepatitis B virus (HBV) infection [based on the status of hepatitis B e antigen (HBeAg), HBV DNA, and cirrhosis] on superimposed acute hepatitis E. METHODS: A total of 294 patients were recruited from the Department of Infectious Diseases of the Third Affiliated Hospital, Sun Yat-sen University, from January 2003 to January 2012. The patients were classified into two groups: an HBV + hepatitis E virus (HEV) group (a group with chronic HBV infection that was superinfected with acute hepatitis E, n = 118) and an HEV group (a group with acute hepatitis E, n = 176). We retrospectively analyzed and compared the clinical features of the two groups. Statistical analyses were performed using the ?2 test or Fisher’s exact test for categorical variables and the Student’s t test for continuous variables. A P value < 0.05 was considered statistically significant. RESULTS: The peak values of prothrombin time, serum total bilirubin, and Model for End-Stage Liver Disease scores were significantly higher in the HBV + HEV group. More patients in the HBV + HEV group had complications (39.8% vs 16.5%, P = 0.000) and developed liver failure (35.6% vs 8.5%, P = 0.000). Additionally, the mortality of the HBV + HEV group was significantly higher (20.3% vs 7.4%, P = 0.002). Further analysis of the HBV + HEV group showed that there were no significant differences in complication occurrence, liver failure incidence, or mortality between patients with different HBeAg and HBV DNA statuses. However, in patients with underlying cirrhosis, complication occurrence and liver failure incidence significantly increased. In total, 12.7% of the patients in the HBV + HEV group received anti-HBV treatment, but this therapy failed to reduce mortality in patients who developed liver failure. CONCLUSION: The presence of underlying cirrhosis in chronic HBV infection results in more severe clinical outcomes with superimposed acute hepatitis E. Anti-HBV treatment cannot improve the prognosis of liver failure caused by HBV-HEV superinfection. PMID:24124337

Cheng, Si-Hong; Mai, Li; Zhu, Feng-Qin; Pan, Xing-Fei; Sun, Hai-Xia; Cao, Hong; Shu, Xin; Ke, Wei-Min; Li, Gang; Xu, Qi-Huan

2013-01-01

66

Prevalence of normal serum amylase levels in patients with acute alcoholic pancreatitis  

Microsoft Academic Search

Acute alcoholic pancreatitis is uncommonly diagnosed when the serum amylase level is normal. We defined acute alcoholic pancreatitis as a clinical syndrome in which hyperamylasemia was not a necessary component and sought support for the diagnosis by ultrasonography and computed tomography of the pancreas. In 68 episodes of acute alcoholic pancreatitis identified in a one-year period, the serum amylase level

Stuart Jon Spechler; John W. Dalton; Alan H. Robbins; Stephen G. Gerzof; Jerry S. Stern; Willard C. Johnson; Donald C. Nabseth; Elihu M. Schimmel

1983-01-01

67

Inpatient management of acute alcohol withdrawal syndrome.  

PubMed

Alcohol withdrawal is a common condition encountered in the hospital setting after abrupt discontinuation of alcohol in an alcohol-dependent individual. Patients may present with mild symptoms of tremulousness and agitation or more severe symptoms including withdrawal seizures and delirium tremens. Management revolves around early identification of at-risk individuals and symptom assessment using a validated tool such as the revised Clinical Institute Withdrawal Assessment for Alcohol score. Benzodiazepines remain the mainstay of treatment and can be administered using a front-loading, fixed-dose, or symptom-triggered approach. Long-acting benzodiazepines such as chlordiazepoxide or diazepam are commonly used and may provide a smoother withdrawal than shorter-acting benzodiazepines, but there are no data to support superiority of one benzodiazepine over another. Elderly patients or those with significant liver disease may have increased accumulation and decreased clearance of the long-acting benzodiazepines, and lorazepam or oxazepam may be preferred in these patients. Patients with symptoms refractory to high doses of benzodiazepines may require addition of a rescue medication such as phenobarbital, propofol or dexmedetomidine. Anticonvulsants (carbamazepine, valproate, gabapentin) may have a role in the management of mild to moderate withdrawal. Other medications such as ?-antagonists or neuroleptics may offer additional benefit in select patients but should not be used a monotherapy. PMID:24781751

Perry, Elizabeth C

2014-05-01

68

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

PubMed Central

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

Affo, Silvia; Morales-Ibanez, Oriol; Rodrigo-Torres, Daniel; Altamirano, Jose; Blaya, Delia; Dapito, Dianne H; Millan, Cristina; Coll, Mar; Caviglia, Jorge M; Arroyo, Vicente; Caballeria, Juan; Schwabe, Robert F; Gines, Pere; Bataller, Ramon; Sancho-Bru, Pau

2014-01-01

69

Histology of symptomatic acute hepatitis C infection in immunocompetent adults.  

PubMed

Acute hepatitis C in immunocompetent individuals is rarely symptomatic and rarely biopsied. Thus, the histologic descriptions of acute hepatitis C remain limited. The histology of 5 cases of acute hepatitis C in adults were studied by selecting cases from the consult and surgical pathology files of a single institution. The 5 individuals, 3 males and 2 females, had an average age at biopsy of 50+/-17 years. They presented with jaundice and other nonspecific abdominal symptoms. The time interval from clinical presentation to biopsy ranged from 2 to 18 weeks. The average alanine aminotransferase/aspartate aminotransferase/alkaline phosphatase at the time of biopsy was 308/73/85 U/L. The average total bilirubin was 5.2 mg/dL. Each individual had a single liver biopsy. The histologic findings of the 2 cases biopsied in close temporal proximity to the initial clinical presentation showed similar histologic findings of mixed portal infiltrates with lymphocytes and neutrophils along with bile ductular proliferation that raised the possibility of down stream biliary tract disease. The lobules showed canalicular cholestasis and mild to moderate inflammation. In the third and fourth case, obtained 8 weeks after presentation, the biopsies showed mild to moderate portal and lobular lymphocytic inflammation, findings that were also present in the last case, obtained 18 weeks after presentation. In conclusion, early after acute hepatitis C viral infection, biopsies can have a cholestatic pattern whereas later biopsies tend to show mild nonspecific portal and lobular lymphocytic inflammation. Proper histologic diagnosis can be aided by an awareness of the various histologic findings, which vary depending on the time interval from clinical symptoms to biopsy. PMID:18059233

Johnson, Kathyrn; Kotiesh, Ayman; Boitnott, John K; Torbenson, Michael

2007-11-01

70

Alcohol Abuse Enhances Pulmonary Edema in Acute Respiratory Distress Syndrome  

PubMed Central

Background Pulmonary edema is a cardinal feature of the life-threatening condition known as Acute Respiratory Distress Syndrome (ARDS). Patients with chronic alcohol abuse are known to be at increased risk of developing and dying from ARDS. Based upon preclinical data, we hypothesized that a history of chronic alcohol abuse in ARDS patients is associated with greater quantities and slower resolution of pulmonary edema compared to ARDS patients without a history of alcohol abuse. Methods A PiCCO™ transpulmonary thermodilution catheter was inserted into 35 patients within 72 hours of meeting American European Consensus Criteria definition of ARDS. Pulmonary edema was quantified as extravascular lung water (EVLW) and measured for up to 7 days in 13 patients with a history of chronic alcohol abuse and 22 patients without a history of chronic alcohol abuse. Results Mean EVLW was higher in patients with a history of chronic alcohol abuse (16.6mL/kg vs. 10.5mL/kg, p<0.0001). Patients with alcohol abuse had significantly greater EVLW over the duration of the study (RM-ANOVA p=0.003). There was a trend towards slower resolution of EVLW in patients with a history of alcohol abuse (a decrease of 0.5mL/kg vs. 2.4mL/kg, p=0.17) over the study period. A history of alcohol abuse conferred a greater than three-fold increased risk of elevated EVLW [OR 3.16, (1.26-7.93)] using multivariate logistic regression analysis. Conclusions In patients who develop ARDS, alcohol abuse is associated with greater levels EVLW and a trend towards slower resolution of EVLW. Combined with mechanistic and preclinical evidence linking chronic alcohol consumption and ARDS, targeted therapies should be developed for these patients. PMID:19572988

Berkowitz, David M.; Danai, Pajman A.; Eaton, Stephanie; Moss, Marc; Martin, Greg S.

2014-01-01

71

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

72

Acute hepatitis E virus infection and autoimmune thyroiditis: yet another trigger?  

PubMed Central

A middle aged woman, previously healthy with the exception of mild seasonal asthma was presented with signs of acute hepatitis. The further investigation showed acute hepatitis E virus infection associated with autoimmune thyroiditis. Treatment was started with propranolol and carbimazol whereupon hepatitis and hyperthyroidism resolved. The authors think that the observed association of acute hepatitis E virus infection and autoimmune thyroiditis suggests a role of hepatitis E virus as putative trigger of autoimmune thyroiditis. The alternative possibility of thyroid dysfunction due to pre-existing autoantibodies cannot be completely excluded but seems to be unlikely given the very mild course of seasonal asthma in this patient. PMID:22604767

Dumoulin, Franz Ludwig; Liese, Hanna

2012-01-01

73

Multiple hepatic mitochondrial DNA deletions suggest premature oxidative aging in alcoholic patients  

Microsoft Academic Search

Background\\/Aims: A 4977-base pair deletion has been detected in the hepatic mitochondrial DNA of alcoholic patients with microvesicular steatosis, a lesion ascribed to impaired mitochondrial ?-oxidation. However, only a single deletion had been looked for in this previous study, and it could not be determined whether the deletion was preexisting or acquired. Alcohol abuse increases the formation of reactive oxygen

Abdellah Mansouri; Bernard Fromenty; Alain Berson; Marie-Anne Robin; Sylvie Grimbert; Michel Beaugrand; Serge Erlinger; Dominique Pessayre

1997-01-01

74

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

PubMed Central

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

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

2012-01-01

75

Acute hepatitis A virus infections in British Gurkha soldiers.  

PubMed

Hepatitis A virus (HAV) and hepatitis E virus (HEV) infections are endemic in most developing countries, including Nepal and Afghanistan, and may cause outbreaks in military personnel. Previously, more than 99% of new British Gurkha recruits were already immune to HAV because of prior infection, but this may be declining due to improved living conditions in their countries of origin. Acute HAV infections have occurred in Gurkha soldiers serving in Afghanistan, which made them unfit for duty for 2-3 months. In one case, early serological diagnosis was impeded by IgM results against both HAV and HEV that were caused by cross-reactivity or persistence from a previous infection. These cases have led to a policy change whereby all Gurkha recruits are now tested for previous HAV infection and if negative they are offered vaccination. Meanwhile, HEV infection remains a significant threat in Nepal and Afghanistan with low levels of background immunity and no commercially available vaccine. PMID:23720504

Green, Chris A; Ross, D A; Bailey, M S

2013-09-01

76

Dynamic Coinfection with Multiple Viral Subtypes in Acute Hepatitis C  

PubMed Central

Introduction. Acute hepatitis C virus (HCV) infection is rarely studied, but virus sequence evolution and hostvirus dynamics during this early stage may influence the outcome of infection. Hypervariable region 1 (HVR1) is genetically diverse and under selective pressure from the host immune response. We analyzed HVR1 evolution by frequent sampling of an acutely infected HCV cohort. Methods. Three or more pretreatment samples were obtained from each of 10 acutely infected subjects. Polymerase chain reaction amplification was performed with multiple primer combinations to identify the full range of sequences present. Positive samples were cloned and sequenced. Phylogenetic analyses were used to assess viral diversity. Results. Eight of the 10 subjects were coinfected with at least 2 HCV subtypes. Multiple subtypes were detected in individual samples, and their relative proportions changed through acute infection. The subjects with the most complex subtype structure also had a dynamic viral load; however, changes in viral load were not directly linked to changes in subtype. Conclusions. This well-sampled cohort with acute HCV infection was characterized by dynamic coinfection with multiple viral subtypes, representing a highly complex virologic landscape extremely early in infection. PMID:21067369

Smith, Jennifer; Aberle, Judith H.; Fleming, Vicki M.; Ferenci, Peter; Thomson, Emma C.; Karayiannis, Peter; McLean, Angela R.; Holzmann, Heidemarie; Klenerman, Paul

2010-01-01

77

Acute Alcohol Use and Suicidal Behavior: A Review of the Literature  

Microsoft Academic Search

Background: Both acute and chronic use of alcohol are associated with suicidal behavior. However, the differing relationship of each component of alcohol use and possible causal mechanisms remain unclear. Methods: This article reviews and summarizes associations between acute alcohol consumption (with and without intoxication) and suicidal behavior (both completed suicide and suicide attempts) among adults 19 years and older, as

Cheryl J. Cherpitel; Guilherme L. G. Borges; Holly C. Wilcox

2004-01-01

78

Acute hepatic injury with atorvastatin: An unusual occurrence  

PubMed Central

Atorvastatin, a commonly used and well-tolerated hypolipidemic drug, belongs to the class of statins or hydroxymethylglutaryl-coenzyme A reductase inhibitors. Use of atorvastatin may be associated with minor asymptomatic elevations in serum aminotransferases, but clinically significant hepatotoxicity is usually infrequent. Here we present a case of self-limiting clinically apparent acute hepatic injury attributable to atorvastatin occurring at recommended daily dose of 20 mg once a day. This case was postulated to be an unusual idiosyncratic reaction of the drug. PMID:24987187

Vishwakarma, Pinki; Nehra, Rajiv; Kumar, Alok

2014-01-01

79

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

80

Investigation of SEN Virus Infection in Patients with Cryptogenic Acute Liver Failure, Hepatitis?Associated Aplastic Anemia, or Acute and Chronic Non–A–E Hepatitis  

Microsoft Academic Search

SEN virus (SENV) has been tentatively linked to transfusion-associated non-A-E hepatitis. We investigated SENV's role in unexplained hepatitis in other settings. Polymerase chain reaction amplification was used to detect 2 SENV variants (SENV-D and SENV-H) in 1706 patients and control subjects. SENV was detected in 54 (22%) of 248 patients with acute or chronic non-A-E hepatitis, 9 (35%) of 26

Takeji Umemura; Eiji Tanaka; George Ostapowicz; Stefan Heringlake; Koji Orii; Angelos Hatzakis; Kendo Kiyosawa

2003-01-01

81

Acute hepatitis induced by an Aloe vera preparation: A case report  

PubMed Central

AIM: Aloe vera, plant extracts of Aloe barbadensis miller, is widely used in phytomedicine. The first case of acute hepatitis due to this compound was described. METHODS: Description of a clinical case. RESULTS: Hepatitis in a 57-year old female could be linked to the ingestion of Aloe barbadensis miller compounds. The patient´s hepatitis resolved completely after discontinuing this medication. CONCLUSION: The case emphasizes the importance of considering phytopharmaceutical over-the-counter drugs as causative agents of hepatitis. PMID:15633238

Rabe, Christian; Musch, Annemarie; Schirmacher, Peter; Kruis, Wolfgang; Hoffmann, Robert

2005-01-01

82

Severe acute hepatitis E in an HIV infected patient: Successful treatment with ribavirin.  

PubMed

In industrialized countries, most cases of hepatitis E virus (HEV) infection in humans are autochthonous, mainly through foodborne and zoonotic transmission routes. In Europe, genotype 3 is a cause of acute self-limiting viral hepatitis, but can also be responsible for chronic hepatitis in immunocompromised patients. Ribavirin has been successfully used in the treatment of chronic hepatitis E and in a few cases of severe acute hepatitis E in immunocompetent patients. We report here the case of a 39 year-old man infected with HIV presenting with acute hepatitis E (genotype 3c). Unlike most cases, evolution was severe with a fall of prothrombin time down to 45%. Treatment with ribavirin allowed rapid viral clearance and a gradual normalization of liver function tests. PMID:24894604

Robbins, A; Lambert, D; Ehrhard, F; Brodard, V; Hentzien, M; Lebrun, D; Nguyen, Y; Tabary, T; Peron, J M; Izopet, J; Bani-Sadr, F

2014-08-01

83

Interleukin-6 regulates hepatic transporters during acute-phase response.  

PubMed

Cholestasis develops during inflammatory conditions characterized by the release of cytokines like interleukin-6 (IL-6), which is the major player in the hepatic acute-phase response. However, the exact contribution of IL-6 to transporter down-regulation is unclear. Therefore, we compared wild-type and IL-6-deficient mice after IL-6-injection and induction of an aseptic (turpentine-injection) or septic (LPS-injection) acute-phase response. Down-regulation of basolateral (Ntcp, Oatp1, and Mrp3) and canalicular (Mrp2, Bsep) transporter mRNA occurred after treatment with IL-6, turpentine, and LPS. In IL-6-deficient mice, turpentine failed to decrease mRNA-levels of basolateral and canalicular transporters, whereas LPS-mediated down-regulation of Ntcp, Mrp3, and Mrp2 was abolished at later time points (24 h). In conclusion, induction of an aseptic and septic acute-phase response leads to the down-regulation of basolateral and canalicular organic anion transporters. IL-6 is required for transporter down-regulation during aseptic inflammation. Furthermore, IL-6 also contributes to transporter regulation during LPS-induced cholestasis at more delayed time points. PMID:15313196

Siewert, Elmar; Dietrich, Christoph G; Lammert, Frank; Heinrich, Peter C; Matern, Siegfried; Gartung, Carsten; Geier, Andreas

2004-09-10

84

Relationship of plasma amino acids to nitrogen balance and portal-systemic encephalopathy in alcoholic liver disease  

Microsoft Academic Search

Plasma amino acids were compared in three groups of patients with alcoholic liver disease including stable cirrhosis, acute alcoholic hepatitis without portal-systemic encephalopathy, and cirrhosis with encephalopathy. In addition, plasma amino acids were correlated with nitrogen balance in patients with acute alcoholic hepatitis and with clinical improvement in patients with encephalopathy. Significant differences in plasma amino acids within these groups

Fredrick L. Weber; Barbara J. Reiser

1982-01-01

85

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

86

Impact of alcohol on hepatitis C virus replication and interferon signaling  

PubMed Central

Hepatitis C virus (HCV) is one of the main etiological factors responsible for liver disease worldwide. It has been estimated that there are over 170 million people infected with HCV worldwide. Of these infected individuals, approximately 75% will go on to develop a life long necroinflammatory liver disease, which over decades, can result in serious complications, such as cirrhosis and hepatocellular carcinoma. Currently there is no effective vaccine and whilst antiviral therapies have been improved, they are still only effective in approximately 50% of individuals. HCV infection stands as a major cause of global morbidity and suffering, and places a significant burden on health systems. The second highest cause of liver disease in the western world is alcoholic liver disease. Frequently, HCV infected individuals consume alcohol, and the combined effect of HCV and alcohol consumption is deleterious for both liver disease and response to treatment. This review discusses the impact of alcohol metabolism on HCV replication and the negative impact on interferon (IFN)-? treatment, with a particular focus on how alcohol and HCV act synergistically to increase oxidative stress, ultimately leading to exacerbated liver disease and a reduction in the efficacy of IFN-? treatment. A better understanding of the complicated mechanisms at play in hepatocytes infected with HCV and metabolizing alcohol will hopefully provide better treatment options for chronic hepatitis C individuals that consume alcohol. PMID:20238400

McCartney, Erin M; Beard, Michael R

2010-01-01

87

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

E-print Network

Acute 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. Methods: With a double-blind independent group design participants were administered alcohol (.4 or .8 g

Burgess, Neil

88

The acute effect of alcohol on decision making in social drinkers  

Microsoft Academic Search

Rationale  Many studies have reported the long-term adverse effects of alcohol on executive cognitive function in chronic alcohol abusers,\\u000a yet little research has investigated the acute effects of alcohol in social drinkers. Studies on acute effects report alcohol-induced\\u000a deficits on tasks that require executive cognitive processes, with alcohol acting to increase preservative errors and reduce\\u000a planning.\\u000a \\u000a \\u000a \\u000a Aim  The present investigation examines the

S. George; R. D. Rogers; T. Duka

2005-01-01

89

Percutaneous aspiration and alcohol sclerotherapy for symptomatic hepatic cysts. An alternative to surgical intervention.  

PubMed Central

Eight patients with 15 symptomatic nonneoplastic congenital hepatic cysts underwent ultrasound-guided percutaneous aspiration and temporary injection of 99% ethanol into the cyst. All cysts were treated at least twice at the same sitting. The volume of alcohol injected varied from 20 to 100 ml, depending on the size of the cyst. A cure was usually achieved with one alcohol sclerotherapy treatment. Only minor side effects such as transient pain and temperature elevation occurred. No recurrences were found during a follow-up period of 12 to 32 months. The results indicate that aspiration and alcohol sclerotherapy is a feasible alternative to surgical intervention in patients with symptomatic nonneoplastic congenital hepatic cysts. We recommend it as the treatment of choice in cases with high surgical risk or polycystic liver disease. Images Figs. 1A-E. Figs. 1A-E. Figs. 2A-I. Figs. 2A-I. Figs. 2A-I. PMID:2667475

Kairaluoma, M I; Leinonen, A; Stahlberg, M; Paivansalo, M; Kiviniemi, H; Siniluoto, T

1989-01-01

90

Acute Hepatitis due to Hepatitis A Virus Subgenotype IA as an Imported Infectious Disease from Indonesia.  

PubMed

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

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

2014-01-01

91

EPIDEMIOLOGY OF ACUTE HEPATITIS IN THE STANN CREEK DISTRICT OF BELIZE, CENTRAL AMERICA  

Microsoft Academic Search

Hepatitis is common in the Stann Creek District of southern Belize. To determine the etiologies, inci- dence, and potential risk factors for acute jaundice, we conducted active surveillance for cases. Cases of jaundice diagnosed by a physician within the previous 6 weeks were enrolled. Evaluation included a questionnaire and labo- ratory tests for hepatitis A, B, C, D, and E,

JOE P. BRYAN; LINDA REYES; SHILPA HAKRE; RUTH GLORIA; GARIKAPARTHI MOHAN KISHORE; WALWYN TILLETT; RONALD ENGLE; SERGEI TSAREV; DAVID CRUESS; ROBERT H. PURCELL

92

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

PubMed

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

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

2014-02-01

93

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

Microsoft Academic Search

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),

Scott Canna; Jennifer Frankovich; Gloria Higgins; Michael R Narkewicz; S Russell Nash; J Roger Hollister; Jennifer B Soep; Leonard L Dragone

2009-01-01

94

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

Microsoft Academic Search

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

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

1996-01-01

95

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

96

Alcohol consumption impairs hepatic protein trafficking: mechanisms and consequences  

PubMed Central

Alcoholic liver disease is a major biomedical health concern in the United States. Despite considerable research efforts aimed at understanding the progression of the disease, the specific mechanisms leading to alcohol-induced damage remain elusive. Numerous proteins are known to have alcohol-induced alterations in their dynamics. Defining these defects in protein trafficking is an active area of research. In general, two trafficking pathways are affected: transport of newly synthesized secretory or membrane glycoproteins from the Golgi to the basolateral membrane and clathrin-mediated endocytosis from the sinusoidal surface. Both impaired secretion and internalization require ethanol metabolism and are likely mediated by acetaldehyde. Although the mechanisms by which ethanol exposure impairs protein trafficking are not fully understood, recent work implicates alcohol-induced modifications on tubulin or components of the clathrin machinery as potential mediators. Furthermore, the physiological ramifications of impaired protein trafficking are not fully understood. In this review, we will list and discuss the proteins whose trafficking patterns are known to be impaired by ethanol exposure. We will then describe what is known about the possible mechanisms leading to impaired protein trafficking and how disrupted protein trafficking alters liver function and may explain clinical features of the alcoholic patient. PMID:19890673

Shepard, Blythe D.; Fernandez, David J.

2009-01-01

97

An Integrated Alcohol Abuse and Medical Treatment Model for Patients with Hepatitis C  

PubMed Central

Background Patients with chronic hepatitis C virus (HCV) infection have high rates of alcohol consumption, which is associated with progression of fibrosis and lower response rates to HCV treatment. Aims This prospective cohort study examined the feasibility of a 24-week integrated alcohol and medical treatment to HCV-infected patients. Methods Patients were recruited from a hepatology clinic if they had an Alcohol Use Disorders Identification Test score ? 4 for women and ? 8 for men, suggesting hazardous alcohol consumption. The integrated model included patients receiving medical care and alcohol treatment within the same clinic. Alcohol treatment consisted of six months of group and individual therapy from an addictions specialist and consultation from a study team psychiatrist as needed. Results Sixty patients were initially enrolled, and 53 patients participated in treatment. The primary endpoint was the Addiction Severity Index (ASI) alcohol composite scores, which significantly decreased by 0.105 (41.7% reduction) between 0 and 3 months (p<.01) and by 0.128 (50.6% reduction) between 0 and 6 months (p<.01) after adjusting for covariates. Alcohol abstinence was reported by 40% of patients at 3 months and 44% at 6 months. Patients who did not become alcohol abstinent had reductions in their ASI alcohol composite scores from 0.298 at baseline to 0.219 (26.8% reduction) at 6 months (p=.08). Conclusion This study demonstrated that an integrated model of alcohol treatment and medical care could be successfully implemented in a hepatology clinic with significant favorable impact on alcohol use and abstinence among patients with chronic HCV. PMID:22134784

Proeschold-Bell, Rae Jean; Patkar, Ashwin A.; Naggie, Susanna; Coward, Lesleyjill; Mannelli, Paolo; Yao, Jia; Bixby, Patricia; Muir, Andrew J.

2013-01-01

98

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

PubMed

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. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'. PMID:23978384

Bjork, James M; Gilman, Jodi M

2014-09-01

99

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

100

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

101

Chronic alcohol intoxication decreases the serum level of hepatitis B surface antigen in transgenic mice.  

PubMed

Hepatitis B virus (HBV) infections with an unusual serological profile, viz. positivity of HBV-DNA in the absence of hepatitis B surface antigen (HBsAg), have been described in alcoholics. This atypical pattern could be due to a low circulating level of viral particles rendering HBsAg undetectable with commercial kits, whereas HBV-DNA remains positive using the highly sensitive hybridization technique. We hypothesize that the well-known alcohol-induced impairment of protein secretion could also concern HBsAg particles and leads to a decrease in serum levels of the HBs antigen. To verify this hypothesis, we used HBsAg-positive transgenic mice as an animal model. Twelve HBsAg+ mice were separated into two groups; one group (n = 6) was submitted to increasing alcoholisation over an 18-week period, while the other (n = 6) was water fed. Seven HBsAg- littermates acted as controls: three received the alcohol regimen and the remaining four water. Chronic excessive alcoholisation lead to a significant decrease in serum HBsAg concentrations, while there was no obvious change in liver S mRNA. Ultrastructural studies showed a significant decrease in the number of microtubules in the livers of alcohol-fed mice. Finally, immunohistochemical studies performed at the end of the experiment showed a greater accumulation of HBsAg in the livers of HBsAg+ alcohol-fed (mainly located in the centrilobular area) than in the HBsAg+ water-fed mice. Our results (i) validate our initial hypothesis that chronic alcohol abuse leads to a decrease in serum HBsAg concentrations. This could explain, in part at least, the serological dissociations which were observed. (ii) Confirm the utility of screening serum HBV-DNA in alcoholics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1506627

Nalpas, B; Pourcel, C; Feldmann, G; Housset, C; Tiollais, P; Bréchot, C; Berthelot, P; Farza, H

1992-05-01

102

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

103

Encephalitis, acute renal failure, and acute hepatitis triggered by a viral infection in an immunocompetent young adult: a case report  

Microsoft Academic Search

INTRODUCTION: Cytomegalovirus generally causes self-limited, mild and asymptomatic infections in immunocompetent patients. An aggressive course in immunocompetent healthy patients is unusual. CASE PRESENTATION: We report the case of an immunocompetent 16-year-old Egyptian boy with encephalitis, acute renal failure, and acute hepatitis triggered by viral infection with a complete recovery following antiviral treatment. CONCLUSION: We believe that this case adds to

Mahmoud Aboelneen Khattab; Mohammed Eslam; Mohammed Emad Abd-elfattah

2009-01-01

104

Investigating an outbreak of acute viral hepatitis caused by hepatitis E virus variants in Karachi, South Pakistan.  

PubMed

Hepatitis E is a classic water-borne disease in developing countries. Detection of anti-HEV IgM and IgG antibodies, in addition to HEV RNA are useful epidemiological markers in diagnosis of hepatitis E. This study was conducted to investigate an outbreak of acute viral hepatitis in South-Pakistan. Anti-HEV IgM and IgG were assessed comparatively with serological kits manufactured by Abbott, Cosmic, TGH, and Wantai, selecting HEV RNA as reference assay. Molecular evolutionary analysis was performed by phylogeny and HEV spread time analysis by Bayesian Coalescent Theory approach. Of the 89 patients, 24 (26.9%) did not have acute hepatitis viral marker. Of the remaining 65 cases, 4 (6.1%) were positive for anti-HAV IgM, one (1.5%) for anti-HBc IgM, 2 (3%) for HCV, 53 (81.5%) for anti-HEV IgM, and 5 (7.7%) were hepatitis-negative. The Wantai test was 100% sensitive and specific followed by Cosmic (98.1% and 100%), TGH (98.1% and 97.2%) and Abbott (79.2% and 83.3%). Two HEV variant strains were detected by phylogeny responsible for this acute hepatitis outbreak. Estimates on demographic history of HEV showed that HEV in Pakistan has remained at a steady nonexpanding phase from around 1970 to the year 2005, in which it expanded explosively with the emergence of new HEV variants. In conclusion, the limited sensitivity of available assay (Abbott anti-HEV EIA) may be a concern in HEV diagnosis in Pakistan. This study cautions that the dissemination of the variant strains to other areas of Pakistan may lead to explosive HEV outbreaks. PMID:21328376

Khan, Anis; Tanaka, Yasuhito; Kurbanov, Fuat; Elkady, Abeer; Abbas, Zaigham; Azam, Zahid; Subhan, Amna; Raza, Sajjad; Razza, Sajjad; Hamid, Saeed; Jafri, Wasim; Shih, James; Xia, Ningshao; Takahashi, Kazuaki; Mishiro, Shunji; Mizokami, Masashi

2011-04-01

105

Genetic Variation in IL28B and Treatment-induced Clearance of Hepatitis C Virus in HIV-Positive Patients With Acute and Chronic Hepatitis C  

PubMed Central

Recently, a IL28B (rs 12979860) gene polymorphism was identified as a predictor for response to hepatits C virus–specific treatment in human immunodeficiency virus (HIV)–uninfected and –infected patients with chronic hepatitis C. In an analysis of HIV-infected patients with acute hepatitis C, we found that the IL28B genotype was associated with serum levels of hepatitis C virus RNA, g-GT, and CD4 cell count. In contrast to HIV-infected patients with chronic hepatitis C, the IL28B genotype was not significantly associated with treatment response rates in patients with acute hepatitis C. Thus, effects of the IL28B single-nucleotide polymorphism may differ in HIV-infected patients with chronic and acute hepatitis C. PMID:21257738

Vogel, Martin; Nischalke, Hans Dieter; Danta, Mark; Mauss, Stefan; Stellbrink, Hans-Jörg; Baumgarten, Axel; Mayr, Christoph; Bruno, Raffaele; Tural, Cristina; Klausen, Gerd; Clotet, Bonaventura; Naumann, Uwe; Lutz, Thomas; Rausch, Michael; Schewe, Knud; Bienek, Bernhard; Haerter, Georg; Sauerbruch, Tilman; Rockstroh, Juergen K.; Spengler, Ulrich

2011-01-01

106

Valproate Treatment of Acute Alcohol Hallucinosis: A Double-Blind, Placebo-Controlled Study  

Microsoft Academic Search

Aims: The aim of this study was to compare the efficacy and safety of valproate (Depakine-Chrono) versus placebo for the treatment of acute alcohol hallucinosis. Methods: 10 days' randomized, double-blind, parallel study was conducted; 40 patients with an ICD-10 diagnosis of acute alcohol hallucinosis were randomized to valproate (Depakine-Chrono) 3000 mg\\/day (n = 20) or placebo (n = 20). The

Zafar N. Aliyev; Nadir A. Aliyev

107

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

108

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

Microsoft Academic Search

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

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

2009-01-01

109

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

110

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

Microsoft Academic Search

The effect of Emblica officinalis fruit extract (EFE) against alcohol-induced hepatic damage in rats was investigated in the present study. In vitro studies\\u000a showed that EFE possesses antioxidant as well nitric oxide (NO) scavenging activity. In vivo administration of alcohol (5 g\\/kg\\u000a b.wt\\/day) for 60 days resulted increased liver lipid peroxidation, protein carbonyls, nitrite plus nitrate levels. Alcohol\\u000a administration also significantly lowers

V. Damodara Reddy; P. Padmavathi; S. Gopi; M. Paramahamsa; N. Ch. Varadacharyulu

2010-01-01

111

Adaptation of Mesenteric Collecting Lymphatic Pump Function Following Acute Alcohol Intoxication  

PubMed Central

Objective Acute alcohol intoxication increases intestinal lymph flow by unknown mechanisms, potentially impacting mucosal immunity. We tested the hypothesis that enhanced intrinsic pump function of mesenteric lymphatics contributes to increased intestinal lymph flow during alcohol intoxication. Methods Acute alcohol intoxication was produced by intragastric administration of 30% alcohol to concious, unrestrained rats through surgically-implanted catheters. Time-matched controls received either no bolus, vehicle, or isocaloric dextrose. Thirty minutes after alcohol administration, rats were anesthetized and mesenteric collecting lymphatics were isolated and cannulated to study intrinsic pumping parameters. In separate experiments, mesenteric lymphatics were isolated to examine direct effects of alcohol on intrinsic pump activity. Results Lymphatics isolated from alcohol-intoxicated animals displayed slgnificantly decreased contraction frequency (CF) than the dextrose group, elevated stroke volume index (SVI) versus all other groups, and decreased myogenic responsiveness compared to sham. Elevating pressure from 2 to 4 cm H2O increased the volume flow index 2.4-fold in the alcohol group versus 1.4-fold for shams. Isolated lymphatics exposed to 20 mM alcohol had reduced myogenic tone, without changes in CF or SVI. Conclusions Alcohol intoxication enhances intrinsic pumping by mesenteric collecting lymphatics. Alcohol directly decreases lymphatic myogenic tone, but effects on phasic contractions occur by an unidentified mechanism. PMID:21040117

Souza-Smith, Flavia M.; Kurtz, Kristine M.; Molina, Patricia E.; Breslin, Jerome W.

2010-01-01

112

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

113

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

114

Clinical Implications of Chemokines in Acute and Chronic Hepatitis C Virus Infection  

PubMed Central

Hepatitis C virus (HCV), a non-cytopathic positive-stranded RNA virus, is one of the most common causes of chronic liver diseases such as chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Upon HCV infection, the majority of patients fail to clear the virus and progress to chronic hepatitis C. Chemokines are small chemotactic cytokines that direct the recruitment of immune cells and coordinate immune responses upon viral infection. Chemokine production during acute HCV infection contributes to the recruitment of immune cells with antiviral effector functions and subsequent viral clearance. In chronic HCV infection, however, continuous production of chemokines due to persistent viral replication might result in incessant recruitment of inflammatory cells to the liver, giving rise to persistence of chronic inflammation and liver injury. In this review, we will summarize the roles of chemokines in acute and chronic settings of HCV infection and the clinical relevance of chemokines in the treatment of hepatitis C. PMID:22028149

Kang, Wonseok

2011-01-01

115

A Case of Acute Hepatitis with Mycoplasma pneumoniae Infection and Transient Depression of Multiple Coagulation Factors  

PubMed Central

We report a case of acute severe hepatitis with Mycoplasma pneumoniae (M. pneumoniae) infection and transient depression of multiple coagulation factors. A 5-year-old boy, previously healthy, was admitted with pneumonia. M. pneumoniae infection was confirmed by serology testing. Liver enzymes were elevated on admission without any past medical history. After treatment with azithromycin for 3 days, pneumonia improved, but the hepatitis was acutely aggravated. Partial thromboplastin time (PTT) was prolonged and depression of multiple coagulation factors developed. Liver biopsy revealed features consistent with acute hepatitis. A week later, liver enzymes were nearly normalized spontaneously. Normalization of prolonged PTT and coagulation factors were also observed several months later. This may be the first case of transient depression of multiple coagulation factors associated with M. pneumoniae infection. PMID:19108034

Chang, Joo Hee; Kwon, Young Se; Kim, Bok Ki; Son, Byong Kwan; Lee, Jee Eun; Lim, Dae Hyun; Kim, Soon Ki; Kim, Joon Mi

2008-01-01

116

Impact of Hepatitis C on HIV Progression in Adults With Alcohol Problems  

PubMed Central

Background Coinfection of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is a substantial medical and public health concern due to its increasing prevalence and complex patient management. Alcohol use may worsen HCV-related liver disease and interfere with adherence to antiretroviral therapy (ART) and medical care. We therefore studied the association between HCV infection and markers of HIV disease progression in adults with alcohol problems. Methods This is a longitudinal study of 396 HIV-infected persons with alcohol problems, 199 (50%) of whom were coinfected with HCV (positive HCV RNA test). CD4 cell counts and HIV RNA levels were assessed at baseline and then every 6 months for up to 42 months. Hepatitis C virus RNA status was determined at study enrollment. We examined the relationship between HCV infection and laboratory markers of HIV progression (CD4 cell count and log10 HIV RNA) by fitting multivariable longitudinal regression models for each outcome. Results Among subjects who were adherent to ART, the presence of HCV infection was associated with a lower CD4 cell count (adjusted mean difference -46.0 cells/?L, p = 0.03). There was no association observed between HCV infection and CD4 cell count among those not adherent to ART or those not taking ART. No significant association was observed between HCV infection and HIV RNA regardless of ART status. Conclusions Hepatitis C virus infection has an adverse effect on CD4 cell count in patients with alcohol problems who are adherent to ART. Addressing HCV coinfection among these patients may confer additional immunologic benefit for this patient population. PMID:17403066

Cheng, Debbie M.; Nunes, David; Libman, Howard; Vidaver, John; Alperen, Julie K.; Saitz, Richard; Samet, Jeffrey H.

2007-01-01

117

Communicating About Alcohol Consumption to Nonharmful Drinkers with Hepatitis C: Patient and Provider Perspectives  

PubMed Central

Background Abstaining from alcohol consumption is generally recommended for patients with Hepatitis C (HCV). However, mixed research findings coupled with a lack of consistent guidelines on alcohol consumption and HCV may influence what healthcare providers tell their HCV patients about drinking. This may be more problematic when advising nonharmful drinkers with HCV, a population for whom consumption would not be a problem in the absence of their HCV diagnosis. Objective This study explores what healthcare providers advise their HCV patients who are drinking alcohol at nonharmful levels about alcohol use and what these patients actually hear. Design We conducted separate focus groups and interviews about alcohol use and HCV with nonharmful drinkers with HCV (N?=?50) and healthcare providers (N?=?14) at a metropolitan teaching hospital. All focus groups and interviews were audio-taped, transcribed, and analyzed using NVivo, a qualitative data management and analysis program. Results We found similar themes about HCV and alcohol consumption (stop completely, occasional drink is ok, cut down, and provision of mixed/ambiguous messages), reported by both providers and patients. Patient respondents who reported hearing “stop completely” were more likely to have had their last medical visit at the gastroenterology (GI) clinic as opposed to the internal medicine (IM) clinic. Furthermore, IM providers were more likely to give their recommendations in “medical language” than were GI providers. Conclusions To make the best health-related decisions about their disease, HCV patients need consistent information about alcohol consumption. Departments of Internal Medicine can increase provider knowledge about HCV and alcohol use by providing more education and training on HCV. PMID:22135843

Blixen, Carol E.; Webster, Noah J.; Hund, Andrew J.; Perzynski, Adam T.; Kanuch, Stephanie W.; Stoller, Eleanor Palo; McCormick, Richard A.

2008-01-01

118

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

119

Case-control study to evaluate risk factors for acute hepatitis B virus infection in Egypt.  

PubMed

Hepatitis B virus (HBV) infection is a significant health problem in Egypt. To better define risk factors associated with HBV transmission, we conducted a case-control study among patients admitted with acute hepatitis to an infectious disease hospital in Cairo. A total of 60 cases and 120 controls were interviewed about various exposures within 6 months prior to admission. Univariate analysis revealed HBV case-patients were more likely to report providing injections to relatives or friends, injecting drug use, exposure to a household contact with hepatitis, exposure to invasive medical procedures and being in the military. Efforts should be made to implement strict infection control standards in Egypt. PMID:20214150

Talaat, M; Radwan, E; El-Sayed, N; Ismael, T; Hajjeh, R; Mahoney, F J

2010-01-01

120

Combination of Oxidative Stress and Steatosis Is a Risk Factor for Fibrosis in Alcohol-Drinking Patients With Chronic Hepatitis C  

Microsoft Academic Search

BACKGROUND AND AIMS:Alcohol and HCV have been shown to interact in stimulating hepatic oxidative damage. Thus, we investigated the contribution of oxidative mechanisms in the progression of chronic hepatitis C (CHC) in alcohol consumers.METHODS: An increased IgG reactivity against lipid peroxidation-derived antigens was used as the marker for alcohol-induced oxidative damage in 125 CHC patients.RESULTS:Alcohol intake significantly increased the frequency

Matteo Vidali; Giuseppa Occhino; Alessandra Ivaldi; Cristina Rigamonti; Massimo Sartori; Emanuele Albano

2008-01-01

121

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

122

Hepatic failure toxins depress liver regenerative enzymes after periportal injury with allyl alcohol in the rat.  

PubMed

Hepatic regenerative enzyme (thymidine kinase and ornithine decarboxylase) activities were significantly depressed by subcoma doses of the hepatic failure toxins (NH4+, octanoic acid, and dimethyl disulfide) after selective injury with allyl alcohol. The inhibitory effect of NH4+ was greater than that of dimethyl disulfide, even though the neurologic effects of dimethyl disulfide were approximately comparable with those of the NH4+. There appeared to be a delay in the full expression of the depressive effects of octanoic acid and dimethyl disulfide. The resistance to these two toxins, particularly dimethyl disulfide, may reflect the resistance to injury of the oxidative processes prominent in periportal hepatocyte mitochondria. In comparison with pericentral injury or two-lobe hepatectomy, periportal injury seemed equally susceptible to regenerative enzyme inhibition by NH4+ but less susceptible to the effect of octanoic acid and dimethyl disulfide. PMID:3373115

Zieve, L; Anderson, W R; LaFontaine, D

1988-06-01

123

Combined effects of alcohol and hepatitis C: a secondary analysis of alcohol use biomarkers and high-risk behaviors from two medication trials for alcohol dependence  

PubMed Central

Objectives This goal of this secondary analysis was to examine the combined effect of HCV infection and recent alcohol use on baseline biologic markers of alcohol consumption in two outpatient medication trials for alcohol dependence. In addition, the relationship between Hepatitis C virus (HCV) infection and behavioral risk factors for HCV infection in these clinical populations were examined. Methods Data (n = 345) from two randomized, placebo-controlled trials of naltrexone and psychosocial treatment for alcohol dependence (Study I, n = 212) and comorbid alcohol and cocaine dependence (Study II, n = 133) were used to examine baseline measures of HCV risk behaviors (injection drug use, needle sharing), and biomarkers of alcohol use (AST, ALT, GGT and CDT) were compared by HCV serostatus first within each study and then across studies. Results Although groups had differing sociodemographic profiles (as indicated by race, marital status, level of education) subjects in Study I exhibited no statistically significant differences from the Study II cohort in HCV prevalence (12.7 vs. 20.0 percent, p = 0.07), lifetime history of injection drug use (13.8 vs. 22.0%, p = 0.74), lifetime history of needle sharing (9.1 vs. 18.0 percent, p = 0.62). As such, the data from both studies were analyzed together. Regardless of drinking status, HCV infection was significantly associated with an upward shift in the baseline level of ALT, AST, and GGT (p<0.006 for all measures) and a downward shift in baseline CDT (p = 0.002). When using standard laboratory cutoff values to determine clinically significant elevations, HCV seropositivity was significantly associated with elevations in ALT, AST, GGT (p<0.001), and with decreases in CDT (p = .002). Conclusions These data emphasize the importance of evaluating HCV infection and HCV risk behaviors at intake in medication trials for alcohol dependence and also raise questions regarding the use of cut off scores for ALT, AST, GGT and CDT levels as biologic markers of alcohol use in subjects when HCV status is unknown. PMID:19783106

Plebani, Jennifer G.; Tirado, Carlos F.; Pettinati, Helen M.; Kampman, Kyle M.; Volpicelli, Joseph R.; Oslin, David W.

2009-01-01

124

The Alternative Substance Paradigm:Effectiveness of Beverage Blinding and Effects on Acute Alcohol Responses  

PubMed Central

A fundamental goal of double-blind alcohol challenge studies is to reduce alcohol expectancies, though there is little research on the effectiveness of blinding procedures and their relationship to acute alcohol responses. This study examined social drinkers’ perception of beverage content and related alcohol response during three separate double-blind experimental sessions with placebo, low dose alcohol (0.4 g/kg), and high dose alcohol (0.8 g/kg). Using the Alternative Substance Paradigm, participants (N=182) were informed that the beverage they consumed might contain alcohol, a stimulant, a sedative, or a placebo. At several timepoints, subjective and objective measures were obtained and participants were asked to identify which substance they received. During both placebo and low dose alcohol sessions, 33% and 50% of participants, respectively, did not correctly identify the beverage content; during the high dose alcohol session, 20% did not correctly identify the beverage. While correct and incorrect identifiers at any dose level did not differ on major background variables, drinking characteristics, or psychomotor performance during these sessions, they did differ on self-reported subjective responses, with greater sedation reported by incorrect identifiers in the placebo and high dose conditions. In sum, results suggest that the Alternative Substance Paradigm may be a viable option for alcohol laboratory studies, particularly for repeated sessions in within-subjects designs and in cases where the experimenter wants to reduce expectancy by not revealing a priori that alcohol is being administered. PMID:22867037

Conrad, Megan; McNamara, Patrick; King, Andrea

2014-01-01

125

Abnormalities in Cu and Zn levels in acute hepatitis of different etiologies  

PubMed Central

Background: Copper (Cu) and Zinc (Zn) are essential trace elements which play an important role in various biological processes. Zn deficiency is common in liver diseases while Cu deficiency is rarely reported. To determine whether serum Cu and Zn concentrations differed in acute hepatitis, compared to controls and investigate possible correlations of Cu and Zn values with etiology and severity of liver diseases. Methods: Serum Cu and Zn concentrations were determined by air acetylene flame atomic absorption spectrometer in 40 patients (acute hepatitis A, B, C, autoimmune and drug induced hepatitis) and 150 healthy controls. Results: Compared to healthy controls, significantly higher Zn levels were found in patients (106.5 ?g/dl, P <0.01). Abnormal levels of either Cu and/or Zn were found in 48% of patients vs 23.3% of the controls (P =0.01). Ten patients had abnormal Zn and fourteen had abnormal Cu levels. There was a trend for the severe hepatitis cases to have abnormal Cu values and in this subgroup Cu and Zn were positively correlated with prothrombin time and alanine aminotransferase (ALT) levels, respectively. Cu and Zn levels did not differ statistically across groups of different etiologies. Conclusions: Abnormalities in Cu and Zn concentrations are common in acute hepatitis. Cu and Zn exhibited positive correlations with prothrombin time and ALT respectively, in severe cases. PMID:25336878

Papanikolopoulos, K; Alexopoulou, A; Dona, A; Hadziyanni, E; Vasilieva, L; Dourakis, S

2014-01-01

126

Alcohol Consumption Decisions among Nonabusing Drinkers Diagnosed with Hepatitis C: An Exploratory Sequential Mixed Methods Study  

PubMed Central

Most studies of decisions to curtail alcohol consumption reflect experiences of abusing drinkers. We employ an exploratory sequential research design to explore the applicability of this research to the experience of nonabusing drinkers advised to curtail alcohol consumption after a Hepatitis C diagnosis. A qualitative component identified 17 new decision factors not reflected in an inventory of factors based on synthesis of existing scales. We triangulated qualitative data by supplementing semi-structured interviews with Internet postings. A quantitative component estimated prevalence and association with current drinking of these new decision factors. Patients who quit drinking tended to attribute post-diagnosis drinking to occasional triggers, whereas patients who were still drinking were more likely to endorse rationales not tied to specific triggers. PMID:20046861

Stoller, Eleanor Palo; Webster, Noah J.; Blixen, Carol E.; McCormick, Richard A.; Hund, Andrew J.; Perzynski, Adam T.; Kanuch, Stephanie W.; Thomas, Charles L.; Kercher, Kyle; Dawson, Neal V.

2009-01-01

127

Aminotransferase changes and acute hepatitis in patients with dengue fever: analysis of 1,585 cases  

Microsoft Academic Search

Introduction: Type 3 dengue virus caused an extensive epidemic in the state of Rio de Janeiro in summer 2002. In some of the patients, it was found in an atypical form with increased aminotransferase levels and acute hepatitis. Material and Methods: An analysis was made of 1,585 serologically confirmed dengue cases at the Dengue Reference Center in Campos dos Goytacazes,

Luiz José de Souza; José Galvão Alves; Rita Maria Ribeiro Nogueira; Carlos Gicovate Neto; Diogo Assed Bastos; Edno Wallace da Silva Siqueira; João Tadeu Damian Souto Filho; Thiago de Abreu Cezário; Carlos Eduardo Soares; Rodrigo da Costa Carneiro

2004-01-01

128

Risks of Chronicity Following Acute Hepatitis B Virus Infection. A Review.  

National Technical Information Service (NTIS)

Hepatitis B virus (HBV) is the cause of one of the most common viral infections of humans (1, 2). A wide range of clinical outcomes are possible following HBV infection. Self-limited, often asymptomatic acute infection most often occurs, but HBV also can ...

1995-01-01

129

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

E-print Network

with a mortality rate of 4%, in particular among young adults, and up to 20% among pregnant women [9]. Obstetric]. A study on maternal and fetal outcomes in India showed that pregnant women with acute hepatitis E had a 2 women in central Africa Mélanie Caron1 , Julie Bouscaillou2 and Mirdad Kazanji1,2* Abstract Background

Paris-Sud XI, Université de

130

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

SciTech Connect

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

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

1996-03-01

131

Semen Hoveniae extract protects against acute alcohol-induced liver injury in mice.  

PubMed

The protective effects of Semen Hoveniae extract (SHE) from Hovenia dulcis Thunb. (Rhamnaceae) on acute alcohol-induced liver injury were investigated in vivo using mice as test models. In the present study, SHE (150, 300, 600 mg/kg/day) was given to mice by intragastric administration for 4 days. Mice were gavaged with 60% ethanol 10 mL/kg after the last dose of extract. Six hours after alcohol administration, liver injury was evaluated by biochemical examination. Lipid peroxidation and the activity of antioxidants were measured by spectrophotometric methods. In mice, administration of SHE significantly decreased the activities of alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum. Administration of SHE also protected against alcohol-induced alcohol dehydrogenase (ADH) elevation in mice. Concurrently, there was an augmentation in the activities of antioxidant enzymes such as superoxide dismutase (SOD), glutathione S-transferase (GST), and glutathione (GSH), and it also facilitated alcohol metabolism. Acute toxicity tests showed that a single dose of oral SHE up to 22 g/kg did not result in any death or toxic side effects in mice during 14 days' observation. These results demonstrate that SHE could protect against acute alcohol-induced liver injury without any toxic side effects. Therefore, Semen Hoveniae has potential for the development of a clinically useful agent which could protect the liver from alcohol-induced injury. PMID:20673184

Du, Jian; He, Da; Sun, Lian-Na; Han, Ting; Zhang, Hong; Qin, Lu-Ping; Rahman, Khalid

2010-08-01

132

Protracted impairment of impulse control under an acute dose of alcohol: a time-course analysis.  

PubMed

Alcohol is well-known for impairing impulse control as well as its disruptive effects on other aspects of behavioral functioning, such as motor control. Time-course analyses during a single dose show rapid development of acute tolerance to impairment of motor coordination, reaction time, and levels of subjective intoxication, but no acute tolerance to impairment of the ability to inhibit responses. Evidence for a possible lag in tolerance development to the impairing effects of alcohol on inhibitory control suggests that, as drinkers' blood alcohol concentration (BAC) declines, they might exhibit prolonged impulsivity despite having an unimpaired ability to initiate action. The present study extended the time-course analysis to examine the recovery of inhibitory control under a dose of alcohol as drinkers' BAC descended from a peak of 80 mg/100ml to a zero level. Twenty-four healthy adults were tested following 0.65 g/kg alcohol and a placebo in a counterbalanced order. They performed a cued go/no-go task that measured response inhibition. They also performed tasks that assessed reaction time, motor coordination, and completed ratings of their subjective levels of intoxication. Alcohol initially impaired inhibitory control, response time, and motor coordination and increased subjective ratings of intoxication. However, acute tolerance to the impairing effects of alcohol was observed for measures of response time, motor coordination, and ratings of intoxication and these measures returned to sober (i.e., placebo) levels by the time BAC fell to near zero. By contrast, impairment of inhibitory control showed no acute tolerance and remained impaired even when drinkers' BAC returned to near zero. Taken together, these results indicate that the disinhibiting effects of alcohol are present even when the impairing effects of alcohol on other aspects of behavior have diminished under the dose. These findings could provide a greater understanding of impulsive behaviors during the descending limb of intoxication. PMID:24286706

Miller, Melissa A; Fillmore, Mark T

2014-11-01

133

Ellagic acid protects Lipopolysaccharide/d-galactosamine-induced acute hepatic injury in mice.  

PubMed

Ellagic acid, a natural polyphenol found in certain fruits, nuts and vegetables, has been reported to have anti-inflammatory, anti-tumor, and antioxidant activities. However, the effects of ellagic acid on acute hepatic injury have not been reported. In the present study, we investigated the effects of ellagic acid on Lipopolysaccharide/d-galactosamine-induced acute hepatic injury in mice. The results showed that LPS/GalN increased hepatic malondialdehyde (MDA) content, TNF-? level, serum ALT and AST levels and TNF-? level. However, these changes were attenuated by ellagic acid. Western blot analysis showed that ellagic acid inhibited LPS/GalN-induced NF-?B activation. Furthermore, ellagic acid induced the expression of Nrf2 and heme oxygenase-1. In conclusion, our results showed that ellagic acid protected against LPS/GalN-induced liver injury by enhancing the antioxidative defense system and reducing inflammatory response. PMID:25038320

Gu, Lei; Deng, Wen-Sheng; Liu, Ye; Jiang, Chun-Hui; Sun, Long-Ci; Sun, Xiao-Fei; Xu, Qing; Zhou, Hong

2014-10-01

134

Interferon gamma production in whole peripheral blood culture in acute hepatitis B.  

PubMed

Interferon gamma (IFNg) production in whole peripheral blood (WPB) and mononuclear (MN) cell culture in acute hepatitis B (AHB) was compared. IFNg production was induced by phytogem agglutinin and measured in the cell supernatants of 14 AHB patients in the course of the disease. There were some up-regulating factors of IFNg production that probably operated in WPB culture: the presence of autoerythrocytes as well as the low content of monocytes. Autoserum regulated IFNg production in a stage-dependent way: it decreased IFNg activity at the bilirubin peak in hepatitis B infection, but not in convalescence. In contrast, we did not find a serum blocking effect in the corresponding stage of acute hepatitis A. The nature of this serum blocking factor in AHB is unclear. PMID:8743107

Osna, N; Duk, A; Sochnev, A

1996-04-01

135

A Randomized, Double-Blinded, Placebo-Controlled Multi-Center Trial of Etanercept in the Treatment of Alcoholic Hepatitis  

PubMed Central

Background Alcoholic hepatitis is a cause of major morbidity and mortality that lacks effective therapies. Both experimental and clinical evidence indicate that the multifunctional cytokine tumor necrosis factor-? (TNF?) contributes to pathogenesis and clinical sequelae of alcoholic hepatitis. A pilot study demonstrated that the TNF?-neutralizing molecule, etanercept, could be an effective treatment for patients with alcoholic hepatitis. Methods Forty-eight patients with moderate to severe alcoholic hepatitis (MELD score ?15) were enrolled and randomized to groups that were given up to 6 subcutaneous injections of either etanercept or placebo for three weeks. Primary study endpoints included mortality at 1- and 6-month timepoints. Results There were no significant baseline differences between the placebo and etanercept groups in demographics or disease severity parameters including age, gender, and MELD score. The 1-month mortality rates of patients receiving placebo and etanercept were similar on an intention-to-treat basis (22.7% versus 36.4%, respectively; OR and 95% CI: 1.8 and 0.5–6.5). The 6-month mortality rate was significantly higher in the etanercept group, compared with the placebo group (57.7% versus 22.7%, respectively; OR and 95% CI: 4.6 and 1.3–16.4, p=0.017). Rates of infectious serious adverse events were significantly higher in the etanercept group, compared with the placebo group (34.6% versus 9.1%, p=0.04). Conclusion In patients with moderate to severe alcoholic hepatitis, etanercept was associated with a significantly higher mortality rate after 6 months, indicating that etanercept is not effective for the treatment of patients with alcoholic hepatitis. PMID:18848937

Boetticher, Nicholas C.; Peine, Craig J.; Kwo, Paul; Abrams, Gary A.; Patel, Tushar; Aqel, Bashar; Boardman, Lisa; Gores, Gregory J.; Harmsen, William S.; McClain, Craig J.; Kamath, Patrick S.; Shah, Vijay H.

2008-01-01

136

Encephalitis, acute renal failure, and acute hepatitis triggered by a viral infection in an immunocompetent young adult: a case report  

PubMed Central

Introduction Cytomegalovirus generally causes self-limited, mild and asymptomatic infections in immunocompetent patients. An aggressive course in immunocompetent healthy patients is unusual. Case presentation We report the case of an immunocompetent 16-year-old Egyptian boy with encephalitis, acute renal failure, and acute hepatitis triggered by viral infection with a complete recovery following antiviral treatment. Conclusion We believe that this case adds to the understanding of the molecular biology, clinical presentation and increasing index of suspicion of many viral infections. PMID:20062779

2009-01-01

137

Acute nonimmune hemolytic anemia without fulminant hepatitis in Wilson disease.  

PubMed

Owing to the insidious course and variable presentation, Wilson disease is often diagnosed months to years after the initial symptoms. Although fulminant hepatitis with nonimmune hemolytic anemia is frequently reported, chronic mild hepatitis can occur with bouts of transient hemolytic anemia. We report a 16-year-old female who presented with fatigue, dizziness, and new onset jaundice. She had a hemolytic anemia, although diagnosis of Wilson disease was initially confounded by a family history of autoimmunity with a high erythrocyte sedimentation rate and only mildly elevated bilirubin and aspartate aminotransferase. Macrocytosis, poor liver synthetic function, and low serum alkaline phosphatase led to the diagnosis. PMID:21516016

Agrawal, Anurag K; Haddad, Fadi G; Matsunaga, Alison

2011-05-01

138

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

139

Functional Imaging of Cognitive Control During Acute Alcohol Intoxication  

PubMed Central

The anterior cingulate and a collection of other prefrontal and parietal brain regions are implicated in error processing and cognitive control. The effects of different doses of alcohol on activity within these brain regions during an fMRI task where errors are frequently committed have not been fully explored. This study examined the impact of a placebo [Breath Alcohol Concentration (BrAC) = 0.00%], moderate (BrAC = 0.05%) and high (BrAC = 0.10%) doses of alcohol on brain hemodynamic activity during a functional MRI (fMRI) Go/No-Go task in thirty-eight healthy volunteers. Alcohol increased reaction time and false alarm errors in a dose-dependent manner. FMRI analyses showed alcohol decreased activity in anterior cingulate, lateral prefrontal cortex, insula and parietal lobe regions during false alarm responses to No-Go stimuli. These findings indicate that brain regions implicated in error processing are affected by alcohol and might provide a neural basis for alcohol's effects on behavioral performance. PMID:20958334

Anderson, Beth M; Stevens, Michael C; Meda, Shashwath; Jordan, Kathryn; Calhoun, Vince D; Pearlson, Godfrey D

2010-01-01

140

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

PubMed Central

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

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

2014-01-01

141

Saliva flow rate, amylase activity, and protein and electrolyte concentrations in saliva after acute alcohol consumption  

Microsoft Academic Search

Objective: The aim of our study was to evaluate the effects of acute alcohol consumption on saliva secretion rate and selected salivary parameters in healthy nonalcoholic volunteers. Study Design: Twenty-four volunteers (37.7 ± 9.6 years, mean ± SD) consumed 0.6 g or 0.7 g alcohol\\/kg of body weight (for women and men, respectively) in a soft drink. Saliva samples were

Nina Enberg; Hannu Alho; Vuokko Loimaranta; Marianne Lenander-Lumikari

2001-01-01

142

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

Microsoft Academic Search

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

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

143

Acute behavioral and cardiac effects of cocaine and alcohol combinations in humans  

Microsoft Academic Search

Subjects received acute doses of orally administered alcohol (0–1.0 g\\/kg) and intranasal cocaine (4–96 mg\\/70 kg) alone and in combination in two experiments. Results generally were consistent across both experiments. Cocaine administered alone improved Digit Symbol Substitution Test (DSST) performance, increased subject ratings of stimulant-like effects, heart rate and blood pressure, and decreased skin temperature. Alcohol administered alone disrupted DSST

Stephen T. Higgins; Craig R. Rush; Warren K. Bickel; John R. Hughes; Mary Lynn; Mark A. Capeless

1993-01-01

144

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

145

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 ...

146

Hepatitis  

MedlinePLUS

... Health Issues > Conditions > Abdominal > Hepatitis Health Issues Listen Hepatitis Article Body Hepatitis means “inflammation of the liver.” ... it has been associated with drinking contaminated water. Hepatitis Viruses Type Transmission Prognosis A Fecal-oral (stool ...

147

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

148

Acute intoxication due to tert-amyl alcohol--a case report.  

PubMed

We presented a case of 28 year-old male, who was found in a deep coma complicated with acute respiratory failure because of recreational intoxication with tert-amyl alcohol (TAA). The TAA blood level at the admission was 83 ?g/mL determined by gas chromatography-mass spectrometry (GC-MS). In the last few months popularity of TAA among alcohol and drug addicted people in Europe is still growing. The main reasons of these are: self-healing of addiction, low price of this xenobiotic compare to alcohol, and problem to detect this xenobiotic in generally used screening tests. PMID:25112153

Anand, Jacek Sein; Giero?, Joanna; Lechowicz, Wojciech; Schetz, Daria; Ka?a, Maria; Waldman, Wojciech

2014-09-01

149

Inappropriate ICD Shocks caused by T-wave Oversensing due to Acute Alcohol Intoxication  

PubMed Central

T-wave oversensing can be a serious problem that often results in inappropriate device therapy. We report here a patient with binge alcohol use who received multiple, inappropriate ICD shocks due to T-wave oversensing from repolarization changes induced by acute alcohol intoxication and no other relevant metabolic derangements. Following recovery from his alcohol intoxication a few days later, the T-wave amplitude decreased so the device no longer inappropriately sensed or delivered therapies. This case represents an uncommon, but reversible cause of T-wave oversensing, that should be considered before more aggressive measures are taken to correct the abnormality. PMID:22385111

Rasania, Suraj P.; Mountantonakis, Stavros; Patel, Vickas V.

2012-01-01

150

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

151

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

E-print Network

Hepatic Ceramide May Mediate Brain Insulin Resistance and Neurodegeneration in Type 2 Diabetes. Keywords Alzheimer's disease; amyloid; diabetes mellitus; high fat diet; insulin resistance, Providence, RI, USA Abstract Obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic steatohepatitis

Hayar, Abdallah

152

Reduced Acute Recovery from Alcohol Impairment in Adults with ADHD  

PubMed Central

Rationale Prior research has found that adults with attention-deficit/hyperactivity disorder (ADHD) show increased sensitivity to the impairing effects of alcohol (Weafer et al. 2009). However, these studies have focused exclusively on the ascending limb of the blood alcohol concentration (BAC) curve, and it is unclear whether these adults continue to show increased sensitivity during the later phase of the dose as BAC is declining. Objective This study tested the hypothesis that those with ADHD would display increased response to alcohol during the ascending limb of the BAC curve and less recovery from the impairing effects during the descending limb. Methods Adult social drinkers with ADHD and control adults completed measures of motor coordination, reaction time, and subjective intoxication twice following 0.64 g/kg alcohol and placebo. The measures were administered during the ascending limb of the BAC curve and again during the descending limb. Results During the ascending limb, alcohol reduced motor coordination, slowed reaction time (RT), and increased self-reports of subjective intoxication. Those with ADHD displayed greater impairment of motor coordination compared with controls. During the descending limb, controls reported diminished subjective intoxication and showed recovery from the impairing effects of alcohol on both their motor coordination and their RT. Those with ADHD showed reduced subjective intoxication and faster RT during this time, but they did not recover motor control. Conclusions The protracted time course of motor impairment in adults with ADHD despite reductions in subjective intoxication may contribute to poor decision making and diminished behavioral control in this group. PMID:23430161

Roberts, Walter; Milich, Richard; Fillmore, Mark T.

2013-01-01

153

Alcohol increases circulatory disease mortality in Russia: acute and chronic effects or misattribution of cause?  

PubMed Central

Background There is a consensus that the large fluctuations in mortality seen in Russia in the past two decades can be attributed to trends in alcohol consumption. However, the precise mechanisms linking alcohol to mortality from circulatory disease remain unclear. It has recently been argued that a substantial number of such deaths currently ascribed to cardiovascular disorders are misclassified cases of acute alcohol poisoning. Methods Analysis of routine mortality data and of a case–control study of mortality among working-age (25–54 years) men occurring in the Russian city of Izhevsk, west of the Ural mountains, 2003–05. Interviews were carried out with proxy informants for both the dead cases (N?=?1750) and the controls (N?=?1750) selected at random from a population register. Mortality was analysed according to indicators of alcohol problems. Results Hazardous drinking was associated with an increased risk of death from circulatory diseases as a whole [odds ratio (OR)?=?4.14, 95% confidence interval (CI) 3.23, 5.31] adjusted for age, smoking and education. The association with alcoholic cardiomyopathy was particularly strong (OR?=?15.7, 95% CI 9.5, 25.9). Although there was no association with deaths from myocardial infarction (MI; OR?=?1.17, 95% CI 0.59, 2.32), there was a strong association with the aggregate of all other ischaemic heart disease (IHD; OR?=?4.04, 95% CI 2.79, 5.84). Stronger associations for each of these causes (other than MI) were seen with whether or not the man had drunk very heavily in the previous week. However, associations also remained when analyses were restricted to subjects with no evidence of recent heavy drinking, suggesting that misclassification of acute alcohol poisonings is unlikely to explain these overall associations. Conclusion Taken as a whole, the available evidence suggests that the positive association of alcohol with increased cardiovascular disease mortality may be best explained as being the result of a combination of chronic and acute alcohol consumption resulting in alcohol-related cardiac disorders, especially cardiomyopathy, rather than being due to misclassification of acute alcohol poisoning. Further work is required to understand the mechanisms underlying the link between heavy alcohol consumption and deaths classified as being due to IHD (other than MI). PMID:20591986

Leon, David A; Shkolnikov, Vladimir M; McKee, Martin; Kiryanov, Nikolay; Andreev, Evgueny

2010-01-01

154

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

PubMed

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

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

2014-10-01

155

Division of Protoplasmic Astrocytes in Acute Experimental Hepatic Encephalopathy  

PubMed Central

The ultrastructural features of dividing protoplasmic astrocytes, induced by the production of hepatic encephalopathy, are described. True cellular hyperplasia, as manifested by cytokinesis at the site of paired nuclei, was demonstrated. The cytoplasm contained structural elements suggesting that cell division occurs by a highly organized process. Some of the observations were similar to those found in mitotic division in other types of cells, raising the possibility that cell division in protoplasmic astrocytosis might occur by mitosis rather than by amitosis, as widely held. ImagesFig 1Fig 2Fig 3 PMID:5021108

Norenberg, Michael D.; Lapham, Lowell W.; Eastland, Mark W.; May, Allyn G.

1972-01-01

156

Microglial proliferation in the brain of chronic alcoholics with hepatic encephalopathy.  

PubMed

Hepatic encephalopathy (HE) is a common complication of chronic alcoholism and patients show neurological symptoms ranging from mild cognitive dysfunction to coma and death. The HE brain is characterized by glial changes, including microglial activation, but the exact pathogenesis of HE is poorly understood. During a study investigating cell proliferation in the subventricular zone of chronic alcoholics, a single case with widespread proliferation throughout their adjacent grey and white matter was noted. This case also had concomitant HE raising the possibility that glial proliferation might be a pathological feature of the disease. In order to explore this possibility fixed postmortem human brain tissue from chronic alcoholics with cirrhosis and HE (n?=?9), alcoholics without HE (n?=?4) and controls (n?=?4) were examined using immunohistochemistry and cytokine assays. In total, 4/9 HE cases had PCNA- and a second proliferative marker, Ki-67-positive cells throughout their brain and these cells co-stained with the microglial marker, Iba1. These cases were termed 'proliferative HE' (pHE). The microglia in pHEs displayed an activated morphology with hypertrophied cell bodies and short, thickened processes. In contrast, the microglia in white matter regions of the non-proliferative HE cases were less activated and appeared dystrophic. pHEs were also characterized by higher interleukin-6 levels and a slightly higher neuronal density . These findings suggest that microglial proliferation may form part of an early neuroprotective response in HE that ultimately fails to halt the course of the disease because underlying etiological factors such as high cerebral ammonia and systemic inflammation remain. PMID:24346482

Dennis, Claude V; Sheahan, Pamela J; Graeber, Manuel B; Sheedy, Donna L; Kril, Jillian J; Sutherland, Greg T

2014-12-01

157

Selenium dietary supplementation as a mechanism to restore hepatic selenoprotein regulation in rat pups exposed to alcohol.  

PubMed

Ethanol exposure during gestation and lactation decreases selenium (Se) intake, disrupting body Se balance and inducing oxidative stress in rat offspring. Selenium-supplemented diet (0.5 ppm) was administered to ethanol-exposed (20% v/v) dams during gestation and lactation. When the dams' pups were 21 days old, the pups' levels of the main hepatic selenoproteins glutathione peroxidase (GPx1 and GPx4) and selenoprotein P (SelP) were measured. The pups were divided into control (C), alcohol (A), control-selenium (CS), and alcohol-selenium (AS) groups. The purpose was to evaluate the effect of the selenium-supplemented diet on the levels of Se deposits present in the livers of their pups. Alcohol decreases hepatic Se deposits, GPx activity, and GPx1 expression; alcohol increases GPx4 and SelP expression. Se was measured by furnace graphite atomic absorption spectrometry, the antioxidant activity of GPx and concentration of hepatic phospholipids (PL) were determined by spectrophotometry, and the selenoprotein expressions were detected by Western blotting. Selenite treatment prevented alcohol's effects of diminishing the Se deposits, GPx activity, and GPx1 expression, while maintaining the high levels of the expression of GPx4 and SelP. These results suggest that depletion of hepatic Se levels in rat pups, caused by ethanol exposure to their dams, affects the synthesis of the 3 main hepatic selenoproteins in different ways, which is related to a decrease in GPx activity and PL concentration, and an increase in serum Se levels. Selenium supplementation to the dams increased the expression of GPx1, GPx4, and SelP in their pups. PMID:24113570

Jotty, Karick; Ojeda, M Luisa; Nogales, Fátima; Murillo, M Luisa; Carreras, Olimpia

2013-11-01

158

Acute inhibition of hepatic beta-oxidation in APOE*3Leiden mice does not affect hepatic VLDL secretion or insulin sensitivity.  

PubMed

Hepatic VLDL and glucose production is enhanced in type 2 diabetes and associated with hepatic steatosis. Whether the derangements in hepatic metabolism are attributable to steatosis or to the increased availability of FA metabolites is not known. We used methyl palmoxirate (MP), an inhibitor of carnitine palmitoyl transferase I, to acutely inhibit hepatic FA oxidation and investigated whether the FAs were rerouted into VLDL secretion and whether this would affect hepatic glucose production. After an overnight fast, male APOE3*Leiden transgenic mice received an oral dose of 10 mg/kg MP. Administration of MP led to an 83% reduction in plasma beta-hydroxybutyrate (ketone body) levels compared with vehicle-treated mice (0.47 +/- 0.07 vs. 2.81 +/- 0.16 mmol/l, respectively; P < 0.01), indicative of impaired ketogenesis. Plasma FFA levels were increased by 32% and cholesterol and insulin levels were decreased by 17% and 50%, respectively, in MP-treated mice compared with controls. MP treatment led to a 30% increase in liver triglyceride (TG) content. Surprisingly, no effect on hepatic VLDL-TG production was observed between the groups at 8 h after MP administration. In addition, the capacity of insulin to suppress endogenous glucose production was unaffected in MP-treated mice compared with controls. In conclusion, acute inhibition of FA oxidation increases hepatic lipid content but does not stimulate hepatic VLDL secretion or reduce insulin sensitivity. PMID:15716584

Duivenvoorden, Ilse; Teusink, Bas; Rensen, Patrick C N; Kuipers, Folkert; Romijn, Johannes A; Havekes, Louis M; Voshol, Peter J

2005-05-01

159

Acute cholestatic hepatitis caused by amoxicillin/clavulanate.  

PubMed

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

2013-12-14

160

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, Andre Loyola

2013-01-01

161

Effect of alcohol exposure on hepatic superoxide generation and hepcidin expression  

PubMed Central

AIM: To understand the role of mitochondrial-produced superoxide (O2•-) in the regulation of iron-regulatory hormone, hepcidin by alcohol in the liver. METHODS: For alcohol experiments, manganese superoxide dismutase knockout mice heterozygous for Sod2 gene expression (Sod2+/-) and age-matched littermate control mice (LMC), expressing Sod2 gene on both alleles, were exposed to either 10% (w/v) ethanol in the drinking water or plain water (control) for 7 d. Total cellular O2•- levels in hepatocytes isolated from the livers of mice were measured by electron paramagnetic resonance spectroscopy. The mitochondrial-targeted, O2•--sensitive fluorogenic probe, MitoSOX Red and flow cytometry were utilized to measure O2•- in mitochondria. Gene and protein expression were determined by Taqman Real-time quantitative PCR and Western blotting, respectively. RESULTS: Sod2+/- mice expressed 40% less MnSOD protein (SOD2) in hepatocytes compared to LMC mice. The deletion of Sod2 allele did not alter the basal expression level of hepcidin in the liver. 10% ethanol exposure for 1 wk inhibited hepatic hepcidin mRNA expression three-fold both in Sod2+/- and LMC mice. O2•- levels in hepatocytes of untreated Sod2+/- mice were three-fold higher than in untreated LMC mice, as observed by electron paramagnetic resonance spectroscopy. O2•- levels in mitochondria of Sod2+/ mice were four-fold higher than in mitochondria of untreated LMC mice, as measured by MitoSOX Red fluorescence and flow cytometry. Alcohol induced a two-fold higher increase in O2•- levels in hepatocytes of LMC mice than in Sod2+/- mice compared to respective untreated counterparts. In contrast, 1 wk alcohol exposure did not alter mitochondrial O2•- levels in both Sod2+/- and control mice. CONCLUSION: Mitochondrial O2•- is not involved in the inhibition of liver hepcidin transcription and thereby regulation of iron metabolism by alcohol. These findings also suggest that short-term alcohol consumption significantly elevates O2•- levels in hepatocytes, which appears not to originate from mitochondria. PMID:24340135

Harrison-Findik, Duygu Dee; Lu, Sizhao; Zmijewski, Emily M; Jones, Jocelyn; Zimmerman, Matthew C

2013-01-01

162

[Acute upper gastrointestinal hemorrhage as a complication of hepatic artery port catheter].  

PubMed

We report a case of a 56-year-old patient with an acute upper gastrointestinal bleeding following penetration of an aneurysm of the gastroduodenal artery in the duodenal bulb. The patient received an i.a. portsystem five month before the reported acute gastrointestinal bleeding. The portsystem was implanted for treatment of multiple liver metastases of an neuroendocrine tumor. This life-threatening situation could not controlled endoscopically. Also an embolisation was impossible so we carried out a laparotomy with ligation of the proper hepatic artery. The postoperative course was uneventful. Due to her tumor disease the patient died 13 month after surgery. PMID:10743039

Reiher, F; Ridwelski, K; Pross, M; Lippert, H

2000-01-01

163

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

164

Sequential occurrence of acute hepatitis B among members of a high school Sumo wrestling club.  

PubMed

A 17-year-old male was admitted to our hospital and diagnosed with acute hepatitis B. Six weeks later, a 15-year-old male was admitted with acute hepatitis B as well. They were Sumo wrestling players in the same club. A detailed survey in the club revealed that a 28-year-old male coach was a hepatitis B surface antigen carrier with high-level viremia. The consistency of hepatitis B virus (HBV) DNA in the infected players was revealed by analyzing the complete HBV genome sequences. Sumo players are more likely to get injured, including cuts and bleeding, compared with players of other sports because of the characteristic wrestling style. Several past reports have suggested that highly viremic HBV carriers have high HBV DNA titers in both their blood and other body fluids such as sweat. In our cases, percutaneous HBV transmission through the bleeding wounds was the most probable infection route. We conclude that a universal HBV immunization program should be introduced urgently in Japan, similar to those implemented in other countries worldwide. PMID:24007264

Bae, Sung Kwan; Yatsuhashi, Hiroshi; Takahara, Ikuko; Tamada, Yoko; Hashimoto, Satoru; Motoyoshi, Yasuhide; Ozawa, Eisuke; Nagaoka, Shinya; Yanagi, Kenji; Abiru, Seigo; Komori, Atsumasa; Ishibashi, Hiromi

2014-10-01

165

Research status of the mechanism and treatment for acute pancreatitis complicated with hepatic injury  

Microsoft Academic Search

Acute pancreatitis (AP) is characterized by its sudden onset and rapid progression and is often complicated by liver injury. AP-induced liver injury may develop into hepatic failure and even result in death. Thus, it is of importance to protect liver function and block injury-related pathways. In the pathogenesis of liver injury in AP, inflammatory cytokines, nuclear factor-kappa B (NF-?B) and

Xiping Zhang; Jie Zhang; Ping Yang

2008-01-01

166

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; Cetin, R?dvan; Cevik, Erdem; C?nar, Orhan

2014-01-01

167

Acute Psychotic Symptoms due to Benzydamine Hydrochloride Abuse with Alcohol.  

PubMed

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; Cetin, R?dvan; Cevik, Erdem; C?nar, Orhan

2014-01-01

168

Identification of two distinct genotypes of hepatitis E virus in a Japanese patient with acute hepatitis who had not travelled abroad  

Microsoft Academic Search

Two distinct hepatitis E virus (HEV) isolates, designated HE-JI3 and HE-JI4, were identified in a single patient with acute hepatitis in Japan, who had not travelled abroad. The HEV load of HE-JI3 at admission was 102 copies\\/ml, but that of HE-JI4 was tenfold higher at 103 copies\\/ml. The viraemia of HE-JI4 persisted for up to 16 days from admission, whereas

Masaharu Takahashi; Tsutomu Nishizawa; Akira Yoshikawa; Shin Sato; Norio Isoda; Kenichi Ido; Kentaro Sugano; Hiroaki Okamoto

2002-01-01

169

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

PubMed

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

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

2004-01-01

170

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

171

Lactobacillus rhamnosus GG culture supernatant ameliorates acute alcohol-induced intestinal permeability and liver injury  

PubMed Central

Endotoxemia is a contributing cofactor to alcoholic liver disease (ALD), and alcohol-induced increased intestinal permeability is one of the mechanisms of endotoxin absorption. Probiotic bacteria have been shown to promote intestinal epithelial integrity and protect barrier function in inflammatory bowel disease (IBD) and in ALD. Although it is highly possible that some common molecules secreted by probiotics contribute to this action in IBD, the effect of probiotic culture supernatant has not yet been studied in ALD. We examined the effects of Lactobacillus rhamnosus GG culture supernatant (LGG-s) on the acute alcohol-induced intestinal integrity and liver injury in a mouse model. Mice on standard chow diet were supplemented with supernatant from LGG culture (109 colony-forming unit/mouse) for 5 days, and one dose of alcohol at 6 g/kg body wt was administered via gavage. Intestinal permeability was measured by FITC-FD-4 ex vivo. Alcohol-induced liver injury was examined by measuring the activity of alanine aminotransferase (ALT) in plasma, and liver steatosis was evaluated by triglyceride content and Oil Red O staining of the liver sections. LGG-s pretreatment restored alcohol-induced reduction in ileum mRNA levels of claudin-1, intestine trefoil factor (ITF), P-glycoprotein (P-gp), and cathelin-related antimicrobial peptide (CRAMP), which play important roles on intestinal barrier integrity. As a result, LGG-s pretreatment significantly inhibited the alcohol-induced intestinal permeability, endotoxemia and subsequently liver injury. Interestingly, LGG-s pretreatment increased ileum mRNA expression of hypoxia-inducible factor (HIF)-2?, an important transcription factor of ITF, P-gp, and CRAMP. These results suggest that LGG-s ameliorates the acute alcohol-induced liver injury by promoting HIF signaling, leading to the suppression of alcohol-induced increased intestinal permeability and endotoxemia. The use of bacteria-free LGG culture supernatant provides a novel strategy for prevention of acute alcohol-induced liver injury. PMID:22538402

Wang, Yuhua; Liu, Yanlong; Sidhu, Anju; Ma, Zhenhua; McClain, Craig

2012-01-01

172

Acute renal and hepatic failure associated with allopurinol treatment.  

PubMed

Hyperuricemia is present in about 5% of the population, and allopurinol is frequently used to treat it. The use of this drug can be associated with a number of side effects, indicating allergic reactions, such as skin rash, reversible after its withdrawal. In some cases more severe hypersensitivity reactions may be seen, such as erythema multiforme exudativum, or Steven-Johnson Syndrome (SJS). Reversible clinical hepatotoxicity, as well as acute renal failure, may also develop after allopurinol therapy. We describe here the case of a 74-year-old woman with chronic renal failure who was admitted to hospital after 1 week of sore throat and fever, presenting mucous membrane lesions, widespread blistering of the skin, evolving to flaccid vesicles and bullae, and extensive epidermal detachment associated with acute renal failure and cholestatic jaundice. A diagnosis of allopurinol-induced toxic epidermal necrolysis (TEN) was established. Allopurinol was discontinued, and intensive care management was required: the patient was successfully treated by using intravenous immunoglobulin (IVIg), standard hemodialysis, and albumin dialysis (Molecular Adsorbents Recirculating System - MARS, Teraklin AG, Rostock, Germany). Allopurinol-induced TEN is extremely rare, however, the survival rate is extremely low. Clinicians should be aware of this potentially severe adverse effect. This report emphasizes the importance of an aggressive pharmacological and dialysis treatment in the case of TEN. PMID:19049711

Fagugli, R M; Gentile, G; Ferrara, G; Brugnano, R

2008-12-01

173

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

PubMed

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, 15 m sprint, countermovement jump, and srummaging performance were assessed pre-simulation and 24 and 48 h post-simulation. White blood cell count, testosterone, cortisol, and creatine kinase were measured before the simulation and 30 min, 12, 24, 36, and 48 h after the simulation. One week after the first trial, participants completed the second simulation after which the other beverage was consumed. The acute consumption of alcohol after a rugby game simulation negatively affected countermovement jump performance in the days following the simulation (P = 0.028). No differences between treatments were observed for the other criterion measures made in this study. In conclusion, after 80 min of a simulated rugby game, the consumption of 1 g of alcohol per kg body mass negatively impacts lower body vertical power output. However, performance of tasks requiring repeated maximal muscular effort is not affected. PMID:22168345

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

2012-01-01

174

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

175

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

176

Acute Overactive Endocannabinoid Signaling Induces Glucose Intolerance, Hepatic Steatosis, and Novel Cannabinoid Receptor 1 Responsive Genes  

PubMed Central

Endocannabinoids regulate energy balance and lipid metabolism by stimulating the cannabinoid receptor type 1 (CB1). Genetic deletion and pharmacological antagonism have shown that CB1 signaling is necessary for the development of obesity and related metabolic disturbances. However, the sufficiency of endogenously produced endocannabinoids to cause hepatic lipid accumulation and insulin resistance, independent of food intake, has not been demonstrated. Here, we show that a single administration of isopropyl dodecylfluorophosphonate (IDFP), perhaps the most potent pharmacological inhibitor of endocannabinoid degradation, increases hepatic triglycerides (TG) and induces insulin resistance in mice. These effects involve increased CB1 signaling, as they are mitigated by pre-administration of a CB1 antagonist (AM251) and in CB1 knockout mice. Despite the strong physiological effects of CB1 on hepatic lipid and glucose metabolism, little is known about the downstream targets responsible for these effects. To elucidate transcriptional targets of CB1 signaling, we performed microarrays on hepatic RNA isolated from DMSO (control), IDFP and AM251/IDFP-treated mice. The gene for the secreted glycoprotein lipocalin 2 (lcn2), which has been implicated in obesity and insulin resistance, was among those most responsive to alterations in CB1 signaling. The expression pattern of IDFP mice segregated from DMSO mice in hierarchal cluster analysis and AM251 pre-administration reduced (>50%) the majority (303 of 533) of the IDFP induced alterations. Pathway analysis revealed that IDFP altered expression of genes involved in lipid, fatty acid and steroid metabolism, the acute phase response, and amino acid metabolism in a CB1-dependent manner. PCR confirmed array results of key target genes in multiple independent experiments. Overall, we show that acute IDFP treatment induces hepatic TG accumulation and insulin resistance, at least in part through the CB1 receptor, and identify novel cannabinoid responsive genes. PMID:22073164

Ruby, Maxwell A.; Nomura, Daniel K.; Hudak, Carolyn S. S.; Barber, Anne; Casida, John E.; Krauss, Ronald M.

2011-01-01

177

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

PubMed Central

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

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

2013-01-01

178

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

179

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

Coban, Hikmet; Yahyaoglu, Mehmet; Vatan, M. Bulent

2014-01-01

180

Little evidence that hepatitis C virus leads to a higher risk of mortality in the absence of cirrhosis and excess alcohol intake: the Swiss Hepatitis C Cohort Study.  

PubMed

The objective of this study was to describe the all-cause mortality of participants in the Swiss Hepatitis C Cohort compared to the Swiss general population. Patients with hepatitis C virus (HCV) infection attending secondary and tertiary care centres in Switzerland. One thousand six hundred and forty-five patients with HCV infection were followed up for a mean of over 2 years. We calculated all-cause standardized mortality ratios (SMR) and 95% confidence intervals (CI) using age, sex and calendar year-specific Swiss all-cause mortality rates. Multivariable Poisson regression was used to model the variability of SMR by cirrhotic status, HCV genotype, infection with hepatitis B virus or HIV, injection drug use and alcohol intake. Sixty-one deaths were recorded out of 1645 participants. The crude all-cause SMR was 4.5 (95% CI: 3.5-5.8). Patients co-infected with HIV had a crude SMR of 20 (95% CI: 11.1-36.1). The SMR of 1.1 (95% CI: 0.63-2.03) for patients who were not cirrhotic, not infected with HBV or HIV, did not inject drugs, were not heavy alcohol consumers (hepatitis C infected patients who were not cirrhotic, in the absence of selected risk factors. Our findings emphasize the importance of providing appropriate preventive advice, such as counselling to avoid alcohol intake, in those infected with HCV. PMID:19243494

Prasad, L; Spicher, V M; Negro, F; Rickenbach, M; Zwahlen, M

2009-09-01

181

Clinical Characteristics, Spontaneous Clearance and Treatment Outcome of Acute Hepatitis C: A Single Tertiary Center Experience  

PubMed Central

Background and Aims: Acute hepatitis C is rarely diagnosed due to its predominantly asymptomatic course. However, early treatment results in viral eradication in a high number of patients thus, preventing chronicity. The aim of our study was to describe our experience with patients with acute hepatitis C virus (HCV) infection who presented and followed-up in our liver unit, pointing on treatment strategy, and outcome. Patients and Methods: Retrospective, descriptive study of 30 patients with acute HCV infection (26 males and 4 females) with a mean age of 32 years. Results: The source of infection was mainly injection drug use in 17/30 (56.7) and medical procedures 6/30 (20%). Twenty patients (66.6%) were symptomatic. HCV-ribonucleic acid (RNA) was detectable at presentation in 26 (86.7%) patients. The genotype distribution was: 13/26 (50%) genotype 1, 3/26 (11.5%) genotype 2, 8/26 (30.8%) genotype 3 and 2/26 (7.7%) genotype 4. Totally, 9 patients (30%) experienced spontaneous viral eradication. No significant differences could be documented between patients who spontaneously cleared the virus and those who had viral persistence. Thirteen patients (44%) were treated with peginterferon-based regimen. All patients (100%) achieved non-detectable HCV-RNA and had normal serum alanine aminotransferase levels at the end of the treatment. Eleven patients achieved sustained virologic response (SVR), one relapsed and one was lost to follow-up. The overall SVR rate was 84.6%. None of the patients required dose reduction or stopped the treatment due to side effects. Conclusion: In conclusion, early initiation of anti-viral treatment in patients with acute hepatitis C results in high-SVR rates (independently of genotype) and is well-tolerated. PMID:23481134

Deutsch, Melanie; Papadopoulos, Nikolaos; Hadziyannis, Emilia S.; Koskinas, John

2013-01-01

182

Metabolomic analysis of arginine metabolism in acute hepatic injury in rats.  

PubMed

To clarify the relationship between arginine metabolism and hepatic injury, metabolomic analysis was performed in rats treated with 3 representative hepatotoxicants, monocrotaline (MCT), concanavalin A (ConA), and ?-naphthyl isothiocyanate (ANIT); or a myotoxicant, tetramethyl-p-phenylenediamine (TMPD). A single dose of MCT, ConA, or ANIT dose-dependently induced hepatocellular necrosis accompanied by decreased blood arginine and increased blood alanine aminotransferase (ALT) and arginase. A close correlation was detected between arginine and ALT (r = -0.746, -0.795, -0.787 for MCT, ConA, ANIT, respectively) or between arginine and arginase (r = -0.605, -0.808, -0.672 for MCT, ConA, ANIT, respectively) in all three hepatic injury models. In contrast, neither hepatocellular necrosis nor alterations in arginine were found in the skeletal muscle injury model, although ALT was slightly increased. An in vitro assay revealed that blood samples obtained from ConA-treated rats transformed external arginine to ornithine, and the reaction was totally inhibited by an arginase inhibitor. These results suggest that blood arginase plays a crucial role in arginine metabolism associated with hepatic injury. In metabolomic analysis, nearly 450 endogenous metabolites were identified in blood obtained from all the models. Among the 13 metabolites involved in arginine metabolism, decreased arginine and increased ornithine occurred in common in the hepatic injury models, whereas citrulline and other metabolites were not altered. These results indicate that arginine metabolism, especially the arginine-to-ornithine pathway, is altered in association with acute hepatic injury. Furthermore, blood arginine and ornithine are possibly specific biomarkers for hepatic injury. PMID:24418708

Saitoh, Wataru; Yamauchi, Shusuke; Watanabe, Kyoko; Takasaki, Wataru; Mori, Kazuhiko

2014-02-01

183

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

184

Acute alcohol consumption aggravates the decline in muscle performance following strenuous eccentric exercise  

Microsoft Academic Search

This study investigated the effects of acute moderate alcohol intake on muscular performance during recovery from eccentric exercise-induced muscle damage. Eleven healthy males performed 300 maximal eccentric contractions of the quadriceps muscles of one leg on an isokinetic dynamometer. They then consumed a beverage containing 1g\\/kg bodyweight ethanol (as vodka and orange juice) (ALC). On another occasion they performed an

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

2010-01-01

185

Ethical considerations regarding early liver transplantation in patients with severe alcoholic hepatitis not responding to medical therapy.  

PubMed

A recent study proposed that liver transplantation may represent life-saving treatment in patients with severe alcoholic hepatitis not responding to medical therapy. In this pilot experience, stringent patient selection resulted in major improvement of short-term survival with low rates of post-transplant alcohol relapse. In the context of organ shortage, which imposes a need for strict selection of transplant candidates, these results raise major ethical questions. Reluctance to perform liver transplantation in alcoholics is based on the fact that alcoholism is frequently considered to be self-inflicted and on fears of harmful post-transplant alcoholism recurrence. A minimal interval of sobriety lasting at least 6 months is a widely adopted criterion for the selection of patients with alcoholic liver disease for liver transplantation. In severe alcoholic hepatitis, the disastrous short-term prognosis in patients not responding to medical therapy does not allow one to reasonably impose an arbitrary period of 6-months of abstinence. This means that these patients must be either systematically excluded from transplantation or selected according to other criteria. Without significant pre-transplant abstinence, it might be argued that these patients do not merit a graft as they have not demonstrated their ability to gain control over their disease through durable modification of their behaviour. Consequently, this procedure could have a negative impact in the public, affecting organ donation and confidence in the fairness of transplant programs. In contrast, ethical principles recommend active treatment of patients, without discrimination, according to the best scientific knowledge. At this stage, we propose that there are no major ethical barriers for further evaluation of this new therapeutic option. The next steps should include transparent communication with the public and further studies to reproduce these results and identify the selection criteria that provide the best long-term outcomes. PMID:24291238

Donckier, Vincent; Lucidi, Valerio; Gustot, Thierry; Moreno, Christophe

2014-04-01

186

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

PubMed Central

Although methamphetamine and alcohol are commonly used together in a binge-like pattern, there is a dearth of empirical data investigating the repeated effects of this drug combination. The current study examined acute and residual mood, performance, and physiological effects of methamphetamine alone, alcohol alone, and the combination. Nine adult male volunteers completed this 20-day within-participant, residential laboratory study. During four 5-day blocks of sessions, participants were administered oral methamphetamine (0, 10 mg) combined with alcohol (0, 0.375, 0.75 g/kg) three times (day 2: AM, day 2: PM, and day 3: PM). Breath alcohol concentrations, cardiovascular, subjective, and cognitive/psychomotor performance effects were assessed before drug administration and repeatedly thereafter. Subjective and objective sleep measures were also assessed; residual effects were assessed on days 3–5 of each block. Following the first drug administration, the methamphetamine–alcohol combination produced greater elevations of heart rate and ratings of “good drug effect” compared to either drug alone. Methamphetamine attenuated alcohol-related performance decrements and feelings of intoxication, whereas alcohol attenuated methamphetamine-related sleep disruptions. By the third administration, many of these effects were significantly diminished, suggesting that participants developed tolerance. Few residual effects were observed. These data show that methamphetamine combined with alcohol produced a profile of effects that was different from the effects of either drug alone. The largely positive effects of the drug combination (i.e., greater euphoria, and fewer performance and sleep disruptions) might explain why these drugs are often used in combination. PMID:21748253

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

2011-01-01

187

Hepatic Angiosarcoma Presenting as an Acute Intraabdominal Hemorrhage Treated with Transarterial Chemoembolization  

PubMed Central

Primary malignant neoplasms of the liver are some of the most uncommon malignancies in many parts of the world. They include hepatocellular carcinoma and stromal tumors such as hepatic angiosarcoma. It is a lethal tumor with life expectancy of less than six months. Once discovered, it is often too late for surgical intervention. Like other vascular tumors of the liver and spleen, intraperitoneal hemorrhage is a well-documented finding of angiosarcoma which can be lethal if not diagnosed and treated immediately. As in our case, intraperitoneal hemorrhage from primary tumor rupture was the only clinical presentation of this neoplasm. Approximately 15% of patients present with acute hemoperitoneum from either tumor rupture or peritoneal metastasis. Although several therapeutic options are available, we describe apalliative therapy for hepatic angiosarcoma utilizing transcatheter arterial chemoembolization (TACE) techniques incorporating the newer embolization agent Embospheres to locally target and treat this aggressive tumor. PMID:18288242

Stambo, Glenn William; Guiney, Michael J.

2007-01-01

188

Temporal pathogenesis of experimental neonatal woodchuck hepatitis virus infection: increased initial viral load and decreased severity of acute hepatitis during the development of chronic viral infection.  

PubMed

Acute hepatitis B virus (HBV) infections either resolve or progress to chronicity. Identification of early deviations in host-virus responses associated with these outcomes can further differentiate cause-effect mechanisms that initiate and maintain chronicity. Neonatal woodchucks were infected experimentally with the woodchuck hepatitis virus (WHV) at 3 days of age. At 8 or 14 weeks of age (i.e. , the early- or mid-acute stage of infection), whole blood and large surgical biopsies of the liver were obtained from infected animals and uninfected controls. These were stored for later correlating histopathologic responses and viral load with the subsequently determined outcome of infection. As of 1 year postinfection, half of the surgically treated infected woodchucks had developed self-limited infections, while the other half developed chronic infections. The self-limited outcome was characterized by decreased viral load in acute-phase liver and plasma and a generally robust acute hepatic inflammatory response. Comparisons at the same early time points revealed that the chronic outcome was characterized by increasing initial viral load in liver and plasma, and a detectable, but diminished, acute hepatic inflammation. These cotemporal comparisons indicate that there is an early host-response deviation during the acute phase of a developing chronic infection. Continued analysis of the tissues banked from this study will facilitate further temporal characterization of acute-phase mechanisms that determine resolution versus chronicity in WHV infection. Understanding such mechanisms may be useful in the rational design of therapy for established chronic HBV infection. PMID:11003627

Cote, P J; Toshkov, I; Bellezza, C; Ascenzi, M; Roneker, C; Ann Graham, L; Baldwin, B H; Gaye, K; Nakamura, I; Korba, B E; Tennant, B C; Gerin, J L

2000-10-01

189

Role of Toll-like receptors 2, 4, and 9 in mediating neutrophil dysfunction in alcoholic hepatitis  

PubMed Central

Neutrophil dysfunction in alcoholic hepatitis is associated with endotoxemia and an increased incidence of infection, but the mechanism is unclear. We aimed to investigate the role of Toll-like-receptors (TLR)2, 4, and 9 in mediating neutrophil dysfunction in alcoholic hepatitis. Neutrophils from healthy volunteers were incubated with alcoholic hepatitis patients’ plasma (n = 12) with and without TLR2, 4, or 9 antagonists and with and without human albumin. TLR2, 4, and 9 expression, neutrophil oxidative burst, phagocytosis, and CXCR1+2 expression were measured by FACS analysis. Patients’ plasma increased oxidative burst, decreased CXCR1+2 expression, and decreased phagocytosis of normal neutrophils in association with increased expression of TLR2, 4, and 9 and depletion of ATP. Inhibition of TLR2, 4, and 9 prevented the increase in oxidative burst and the decrease in CXCR1 and CXCR2 expression but did not prevent phagocytic dysfunction. Incubation with albumin completely prevented the patient plasma induced neutrophil dysfunction. Increased expression of TLR2, 4, and 9 is associated with neutrophil dysfunction, endotoxemia, and energy depletion. TLR2, 4, and 9 inhibition does not improve phagocytosis, indicating that TLR overexpression may be the result and not the cause of neutrophil activation. Albumin, an endotoxin scavenger, prevents the deleterious effect of patients’ plasma on neutrophil phagocytosis, resting burst, and TLR expression. PMID:19033535

Stadlbauer, V.; Mookerjee, R. P.; Wright, G. A. K.; Davies, N. A.; Jurgens, G.; Hallstrom, S.; Jalan, R.

2009-01-01

190

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

191

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

192

[Efficiency of groprinosine in the complex treatment of acute virus hepatitis B].  

PubMed

35 patients with acute virus hepatitis of average severity were examined. They developed after short-term improvement of general state a negative dynamics of clinical and laboratory indexes. 21 patients have received traditional treatment, 14 patients additionally were prescribed groprinosine in a dose of 50 mg/kg daily per/os within 5-10 days. It was shown, that addition of gropfmosme to complex therapy positively influenced on the disease's course, promoted a rapid regress of clinical symptoms, normalization of biochemical indexes of liver's functions and decreased days of hospitalization. PMID:15724621

Karimov, I Z

2004-01-01

193

Effects of Acute Hyperglucagonemia on Hepatic and Intestinal Lipoprotein Production and Clearance in Healthy Humans  

PubMed Central

OBJECTIVE The metabolism of hepatic- and intestinally derived lipoproteins is regulated in a complex fashion by nutrients, hormones, and neurologic and other factors. Recent studies in animal models suggest an important role for glucagon acting via the glucagon receptor in regulating hepatic triglyceride (TG) secretion. Here we examined the direct effects of glucagon on regulation of hepatic and intestinal lipoprotein metabolism in humans. RESEARCH DESIGN AND METHODS Eight healthy men underwent two studies each, in random order, 4–6 weeks apart in which de novo lipogenesis, kinetics of larger VLDL1 TG, and kinetics of VLDL1 and smaller VLDL2 apolipoprotein (apo)B100 and B48 were studied using established stable isotope enrichment methods. Subjects were studied in the constant fed state under conditions of a pancreatic clamp (with infusion of somatostatin, insulin, and growth hormone) at either basal glucagon (BG study, 64.5 ± 2.1 pg/mL) or hyperglucagonemia (high glucagon [HG] study, 183.2 ± 5.1 pg/mL). RESULTS There were no significant differences in plasma concentration of VLDL1 or VLDL2 TG, apoB100 or apoB48 between BG and HG studies. There was, however, lower (P < 0.05) VLDL1 apoB100 fractional catabolic rate (?39%) and production rate (?30%) in HG versus BG, but no difference in de novo lipogenesis or TG turnover, and glucagon had no effect on intestinal (B48-containing) lipoprotein metabolism. CONCLUSIONS Glucagon acutely regulates hepatic but not intestinal lipoprotein particle metabolism in humans both by decreasing hepatic lipoprotein particle production as well as by inhibiting particle clearance, with no net effect on particle concentration. PMID:20980459

Xiao, Changting; Pavlic, Mirjana; Szeto, Linda; Patterson, Bruce W.; Lewis, Gary F.

2011-01-01

194

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

PubMed

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

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

2014-10-15

195

One year follow-up of patients treated with misoprostol in acute phase of viral hepatitis B  

Microsoft Academic Search

The study was undertaken to determine the long-term effect of misoprostol, on hepatitis B virus (HBV) elimination in patients treated during acute phase of viral hepatitis B. Forty male patients were evaluated 12 months after treatment with misoprostol (M-group) or sylimarin (S-group). HBsAg clearance, as an indicator of HBV elimination, and serum bilirubin concentration, prothrombin index, and activities of alanine

Robert Flisiak; Danuta Prokopowicz

2000-01-01

196

Awareness of Hepatitis C Diagnosis is Associated with Less Alcohol Use Among Persons Co-Infected with HIV  

PubMed Central

BACKGROUND AND OBJECTIVE It is unknown whether testing HIV-infected individuals for hepatitis C virus (HCV) and informing them of their HCV status impacts subsequent alcohol use. We hypothesized that HIV-infected individuals with current or past alcohol problems who reported being told they had HCV were more likely to 1) abstain from alcohol and 2) not drink unhealthy amounts compared to individuals who had not been told. DESIGN, PARTICIPANTS, AND MEASUREMENTS Data from a prospective, observational cohort study (HIV-Longitudinal Interrelationships of Viruses and Ethanol) were used to assess the association between awareness of having HCV at baseline and subsequent abstinence and not drinking unhealthy amounts as reported at 6-month follow-up intervals. General estimating equations logistic regression was used to account for the correlation from using repeated observations from the same subject over time. We adjusted for age, sex, race, homelessness, injection drug use, depressive symptoms, and having abnormal liver tests. RESULTS Participants who reported being told they had HCV were more likely to report abstaining from alcohol (AOR?=?1.60; 95% CI: 1.13 to 2.27) and not drinking unhealthy amounts (AOR?=?1.46; 95% CI: 1.01 to 2.11). CONCLUSIONS Among patients infected with HIV who had a history of alcohol problems, reporting being told one had HCV was associated with greater abstinence from alcohol and less unhealthy amounts of drinking. PMID:17503108

Saitz, Richard; Cheng, Debbie M.; Nunes, David; Libman, Howard; Alperen, Julie K.; Samet, Jeffrey H.

2007-01-01

197

Hepatitis  

Microsoft Academic Search

Blood-borne viral infections have implications for anaesthesia and intensive care because of their potential for transmission and as disease entities. An increasing number of hepatotropic viruses have been identified and may be acquired from faecal contamination (hepatitis A and E) or parenterally via body fluids (hepatitis B, C, D and G). These hepatotropic viruses preferentially cause hepatitis and exhibit this

Rick Keays

2004-01-01

198

Acute lung injury following transcatheter hepatic arterial chemoembolization of doxorubicin-loaded LC beads in a patient with hepatocellular carcinoma.  

PubMed

Transcatheter arterial chemoembolization (TACE) currently is being used as an effective palliative therapy for unresectable cancers especially hepatocelluar carcinoma (HCC). Accidental lipiodol embolism to the lungs is a rare but potentially fatal complication of TACE. This procedure involves injection of drug-eluting microspheres (LC Bead) loaded with doxorubicin, followed by embolization with embozene microspheres until stasis is evident, being used in advanced HCC. We report a patient with inoperable HCC with underlying Hepatitis C and liver cirrhosis, who developed acute lung injury following targeted chemoembolization of selective feeding hepatic artery with LC beads loaded with doxorubicin. Acute lung injury as a complication of unintended lung chemoembolization with doxorubicin has not been previously reported in the literature. Interventional radiologists screen patients for potential hepatic A-V shunt and take appropriate precautions to prevent unintended pulmonary embolization. These include appropriate selection of LC bead particle size especially in patients who are embolized with radiation pellets. This report highlights the need for a screening total body scintigraphy after injection of radionuclide Tc-99 MAA in the feeding hepatic artery to identify patients with hepatic A-V shunt. In such patients, appropriate size selection of LC bead particles is critical to prevent unintended pulmonary chemoembolization and acute lung injury. Other measures include careful patient selection, low dose of chemotherapy, and transient selective hepatic vein balloon occlusion. PMID:22628935

Khan, Ihsan; Vasudevan, Viswanath; Nallagatla, Sasikanath; Arjomand, Farhad; Ali, Rana

2012-04-01

199

[Viral hepatitis].  

PubMed

Viral hepatitis is associated with significant morbidity and mortality worldwide. Hepatitis A and E viruses are enterally transmitted and lead to usually self-limited acute hepatitis. Hepatitis B, C and D viruses are transmitted by parenteral routes and can lead to chronic hepatitis with progression to liver cirrhosis and hepatocellular carcinoma. Here, we briefly review current understanding and new developments in the virology and epidemiology, diagnosis, natural history, therapy and prevention of viral hepatitis. PMID:21452137

Moradpour, Darius; Blum, Hubert E

2011-04-01

200

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

201

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 ...

202

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 ...

203

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

204

Acute fulminant hepatitis E virus genotype 3e infection: Description of the first case in Europe.  

PubMed

Abstract Hepatitis E virus (HEV) is the most important causative agent of acute hepatitis in developing countries. The disease is usually characterized by a self-limiting, benign course. However, when particular conditions coexist (pregnancy, old age, pre-existing liver disease) it may run an unfavourable course. To date, 4 HEV genotypes have been described. Historically, in the Western world, HEV infection was considered a travel-related disease, however in the last 2 decades a great number of non-travel-related autochthonous cases have been described, more often related to genotype 3 or 4 and in the context of zoonosis. We report the case of an elderly Italian man with an acute fulminant HEV infection genotype 3e that developed in the context of pre-existing liver disease; this is the first case of an unfavourable outcome associated with subgenotype 3e. The potential pathogenicity of this subgenotype together with the influence of host-related risk factors are discussed. PMID:25134653

Festa, Stefano; Garbuglia, Anna Rosa; Baccini, Flavia; Panzuto, Francesco; Capobianchi, Maria Rosaria; Santino, Iolanda; Purchiaroni, Flaminia; Orgera, Gianluigi; Delle Fave, Gianfranco; Marignani, Massimo

2014-10-01

205

ACTIVATION OF NATURAL KILLER CELLS DURING ACUTE INFECTION WITH HEPATITIS C VIRUS  

PubMed Central

Background and Aims NK cells are essential early after infection not only for viral containment but also for timely and efficient induction of adaptive responses. An inhibitory effect of HCV-E2 proteins on NK cells has been reported but the features of NK cell responses in the acute phase of hepatitis C are still largely undefined. Therefore, the aim of this study was to characterize function and phenotype of natural killer cells in the acute phase of infection and compare individuals with chronic and self-limited outcomes. Methods Twenty-two individuals with acute HCV infection, 14 with chronic evolution and 8 with self-limited infection, were studied using NK phenotypic and functional assays. Results An increased expression of NKG2D on both CD56bright and CD56dim NK cells was detected in acute HCV patients, irrespective of the outcome, as compared to healthy controls. Also IFN-? production and cytotoxicity by NK cells were higher in individuals with acute HCV infection than in healthy controls. Subset analysis demonstrated an increased IFN-? production in both NK cell subsets carrying group 1 and group 2 HLA-C specific KIRs. However, increased CD107a was noted only on NK cells expressing the group 1 HLA-C specific KIR and was maximal in self-limited infection. Conclusions Our data demonstrate that in the acute phase of HCV infection NK cells are activated regardless of outcome with no evidence of a suppressive effect of HCV on NK cell function. PMID:20080094

Amadei, Barbara; Urbani, Simona; Cazaly, Angelica; Fisicaro, Paola; Zerbini, Alessandro; Ahmed, Parvin; Missale, Gabriele; Ferrari, Carlo; Khakoo, Salim I

2014-01-01

206

Alterations in natural killer cells and natural killer T cells during acute viral hepatitis E.  

PubMed

The mechanism of liver damage in acute hepatitis E is poorly understood. In this study, we assessed the frequency and activation status of natural killer (NK) and natural killer T (NKT) cells and cytotoxic activity of NK cells in the peripheral blood mononuclear cells (PBMCs) obtained from patients with hepatitis E (n = 41) and healthy controls (n = 61). Flow cytometry was used to assess NK (CD3(-)/CD56(+)) and NKT cell (CD3(+)/CD56(+)) fractions (% of PBMCs) and activation status (CD69(+); % of NK, NKT cells). NK cell cytotoxicity was assessed using major histocompatibilities complex-deficient K562 cells as target cells. In 14 patients, the studies were repeated during the convalescence period. Patients had fewer median (range) NK cells [8.9% (2.4-47.0) vs 11.2% (2.6-35.4)] and NKT cells [8.7% (2.8-34.1) vs 13.6% (2.3-36.9)] than controls (P < 0.05 each). Activation markers were present on large proportion of NK cells [43.5% (11.2-58.6) vs 15.5% (3.0-55.8)] and NKT cells [41.5% (17.4-71.1) vs 12.8% (3.3-63.2); P < 0.05 each] from patients. NK cell cytotoxicity was similar in patients and controls. During convalescence, all the parameters normalized. In conclusion, reversible alterations in NK and NKT cell number and activation status during acute hepatitis E suggest a role of these cells in the pathogenesis of this disease. PMID:18673427

Srivastava, R; Aggarwal, R; Bhagat, M R; Chowdhury, A; Naik, S

2008-12-01

207

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

PubMed Central

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

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

2013-01-01

208

Changes in cerebral CB1 receptor availability after acute and chronic alcohol abuse and monitored abstinence.  

PubMed

Involvement of the type 1 cannabinoid receptor (CB1R) in the effects of alcohol on the brain is supported by animal experiments, but how in vivo CB1R levels are altered in alcoholic patients is still unclear. To assess the short-time effects of a binge drinking episode on CB1R availability, 20 healthy social drinkers underwent [(18)F]MK-9470-positron emission tomography (PET) at baseline and after intravenous ethanol administration (ALC ACU). Moreover, 26 alcoholic patients underwent sequential CB1R PET after chronic heavy drinking (ALC CHR) and after 1 month of abstinence (ALC ABST). Seventeen healthy subjects served as controls. Compared with baseline, ALC ACU resulted in a global increase of CB1R availability (+15.8%). In contrast, a global decreased CB1R availability was found in ALC CHR patients (-16.1%) compared with controls, which remained unaltered after abstinence (-17.0%). Voxel-based analysis showed that ALC CHR patients had reduced CB1R availability, especially in the cerebellum and parieto-occipital cortex. After abstinence, reduced CB1R availability extended also to other areas such as the ventral striatum and mesotemporal lobe. In conclusion, whereas the acute alcohol effect is an increase in CB1R availability, chronic heavy drinking leads to reduced CB1R availability that is not reversible after 1 month of abstinence. Longer follow-up is required to differentiate whether this is a compensatory effect of repeated endocannabinoid overstimulation or an enduring trait-like feature. An enhanced CB1R signaling may offer a new therapeutic direction for treatment of the negative affective state produced by alcohol withdrawal and abstinence, which is critical for the maintenance of alcohol addiction. PMID:24553924

Ceccarini, Jenny; Hompes, Titia; Verhaeghen, Anne; Casteels, Cindy; Peuskens, Hendrik; Bormans, Guy; Claes, Stephan; Van Laere, Koen

2014-02-19

209

[Methyldopa-induced acute reactive hepatitis in pregnancy, drug-metabolizing capacity of the liver].  

PubMed

Alpha-methyldopa is a regularly used antihypertensive drug during pregnancy. Methyldopa, which decreases the sympathoadrenal system, is the first drug of choice since decades. The reactive hepatitis is not frequent, but known serious side effect of alpha-methyldopa. In non-pregnant women the estimated rate of manifest hepatotoxicity is 2.5-10%. In our case, gestation hypertension developed at the 21st gestation week of a 35 year-old pregnant woman. Oral methyldopa, a central alpha adrenergic blocker therapy was introduced. On the 23rd gestation week acute hepatitis developed. During differential diagnosis of hepatitis, the etiology of methyldopa was taken into account. Viral and autoimmune origin was rolled out. No fetal aberration was found during ultrasound examination. The function of drug metabolizing function from blood was measured by CYP phenotyping (CYP gene expression analysis). CYP3A4 enzyme plays a primary role in the metabolism of nifedipine. Antihypertensive therapy was changed from methyldopa to nifedipine. Nifedipine dosage was based on the value of CYP3A4 gene expression. With the reduced nifedipine therapy (30 mg daily), blood pressure was successfully under control. The diagnosis of alpha-methyldopa induced hepatitis was based on anamnesis, clinical picture and the results of chemical and radiological examination and confirmed by the level of drug-metabolizing capacity. The gestation hepatotoxicity of alpha-methyldopa was reported first in 1969 by Elkington Smith, who suggested the monitoring of serum aminotransferase during alpha-methyldopa therapy in pregnancy in their case report. Our case report confirms that monitoring of serum aminotransferase level is still valuable when treating a pregnant woman with alpha-methyldopa. PMID:20211808

Ozsvár, Zsófia; Solymossi, Zsuzsa; Monostory, Katalin

2010-03-14

210

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

PubMed

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

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

2014-06-01

211

Comparison of histopathology in acute allograft rejection and recurrent hepatitis C infection after liver transplantation.  

PubMed

Recurrent hepatitis C infection after orthotopic liver transplantation (OLT) is frequent and may occur as early as a few weeks postoperatively. Early histopathological features of recurrent hepatitis C virus (HCV) infection may be modified by immunosuppressive therapy and can be difficult to differentiate from acute allograft rejection (AAR). Thus, we retrospectively compared histopathological features of liver biopsy specimens from two carefully selected patient groups: one with unequivocal recurrent hepatitis C, the other with unequivocal AAR. Index biopsy specimens obtained at the time of the appearance of liver test abnormalities after OLT and all serial liver biopsy specimens (2 to 13 per patient) were assessed under code and scored semiquantitatively for 44 histopathological variables. The index biopsy specimens from patients with recurrent HCV infection and AAR index biopsies (AAR-Ib) differed significantly (P < .05) for 11 features (10 features were statistically associated with AAR and 1 with early recurrence of HCV infection). Statistically significant features associated with AAR included bile duct injury with overlapping nuclei, lymphocytic infiltrates and necrosis, endothelialitis, portal inflammatory infiltrates containing eosinophils and polymorphonuclear leukocytes, hepatocyte mitoses, and zone 3 canalicular cholestasis. In contrast, the only statistically significant feature associated with early recurrent HCV was sinusoidal dilatation. Stepwise discriminant analysis showed that the presence of eosinophils in the portal inflammatory infiltrate, bile duct necrosis, and bile duct lymphocytic infiltrates were independently associated with AAR. However, serial biopsy specimens from patients with recurrent HCV infection showed statistically significant progression in scores for portal inflammation, portal lymphoid aggregates, and lobular inflammation. We conclude that (1) multiple histopathological features are associated with AAR; (2) early recurrent HCV infection is characterized by elevated alanine aminotransferase levels, positive HCV RNA by polymerase chain reaction (PCR), and absence of diagnostic histopathological features; and (3) serial biopsies are needed to demonstrate progression of histopathological features of recurrent hepatitis C. PMID:9346770

Petrovic, L M; Villamil, F G; Vierling, J M; Makowka, L; Geller, S A

1997-07-01

212

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

213

Acute lymphocytic crisis following herpes simplex type 1 virus hepatitis in a nonimmunocompromised man: a case report  

Microsoft Academic Search

INTRODUCTION: An increase in circulating lymphocytes can be seen following infections such as infectious mononucleosis and pertussis, or in lymphoproliferative disorders such as acute and chronic lymphocytic leukemia. Acute lymphocytic crisis following herpes simplex virus hepatitis has not been described in the literature. CASE PRESENTATION: A 52-year-old man was admitted to our hospital reporting low-grade fever for the previous seven

Sotiris Plastiras; Ourania Kampessi

2009-01-01

214

Microtubule Acetylation and Stability May Explain Alcohol-Induced Alterations in Hepatic Protein Trafficking  

PubMed Central

We have been using polarized hepatic WIF-B cells to examine ethanol-induced liver injury. Previously, we determined microtubules were more highly acetylated and more stable in ethanol-treated WIF-B cells. We proposed that the ethanol-induced alterations in microtubule dynamics may explain the ethanol-induced defects in membrane trafficking that have been previously documented. To test this, we compared the trafficking of selected proteins in control cells and cells treated with ethanol or with the histone deacetylase 6 inhibitor trichostatin A (TSA). We determined that exposure to 50 nM TSA for 30 minutes induced microtubule acetylation (~3-fold increase) and stability to the same extent as did ethanol. As shown previously in situ, the endocytic trafficking of the asialoglycoprotein receptor (ASGP-R) was impaired in ethanol-treated WIF-B cells. This impairment required ethanol metabolism and was likely mediated by acetaldehyde. TSA also impaired ASGP-R endocytic trafficking, but to a lesser extent. Similarly, both ethanol and TSA impaired transcytosis of the single-spanning apical resident aminopeptidase N (APN). For both ASGP-R and APN and for both treatments, the block in trafficking was internalization from the basolateral membrane. Interestingly, no changes in transcytosis of the glycophosphatidylinositol-anchored protein, 5?-nucleotidase, were observed, suggesting that increased microtubule acetylation and stability differentially regulate internalization. We further determined that albumin secretion was impaired in both ethanol-treated and TSA-treated cells, indicating that increased microtubule acetylation and stability also disrupted this transport step. Conclusion These results indicate that altered microtubule dynamics explain in part alcohol-induced defects in membrane trafficking. PMID:18161881

Joseph, Rohan A.; Shepard, Blythe D.; Kannarkat, George T.; Rutledge, Tara M.; Tuma, Dean J.; Tuma, Pamela L.

2010-01-01

215

Feature Hepatitis: The Dangers of Hepatitis: What you should know from A to E  

MedlinePLUS

... Navigation Bar Home Current Issue Past Issues Feature Hepatitis The Dangers of Hepatitis: What you should know from A to E ... drugs. In some cases, hepatitis lasts a lifetime. Hepatitis: Acute or Chronic? Acute hepatitis is the initial ...

216

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

PubMed

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

217

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; Buchler, M W; Fortunato, F

2013-01-01

218

Octacosanol Attenuates Disrupted Hepatic Reactive Oxygen Species Metabolism Associated with Acute Liver Injury Progression in Rats Intoxicated with Carbon Tetrachloride  

PubMed Central

We examined whether octacosanol, the main component of policosanol, attenuates disrupted hepatic reactive oxygen species metabolism associated with acute liver injury progression in rats intoxicated with carbon tetrachloride (CCl4). In rats intoxicated with CCl4 (1 ml/kg, i.p.), the activities of serum transaminases increased 6 h after intoxication and further increased at 24 h. In the liver of CCl4-intoxicated rats, increases in lipid peroxide (LPO) concentration and myeloperoxidase activity and decreases in superoxixde dismutase activity and reduced glutathione (GSH) concentration occurred 6 h after intoxication and these changes were enhanced with an increase in xanthine oxidase activity and a decrease in catalase activity at 24 h. Octacosanol (10, 50 or 100 mg/kg) administered orally to CCl4-intoxicated rats at 6 h after intoxication attenuated the increased activities of serum transaminases and the increased hepatic myeloperoxidase and xanthine oxidase activities and LPO concentration and the decreased hepatic superoxide dismutase and catalase activities and GSH concentration found at 24 h after intoxication dose-dependently. Octacosanol (50 or 100 mg/kg) administered to untreated rats decreased the hepatic LPO concentration and increased the hepatic GSH concentration. These results indicate that octacosanol attenuates disrupted hepatic reactive oxygen species metabolism associated with acute liver injury progression in CCl4-intoxicated rats. PMID:18385828

Ohta, Yoshiji; Ohashi, Koji; Matsura, Tatsuya; Tokunaga, Kenji; Kitagawa, Akira; Yamada, Kazuo

2008-01-01

219

Hepatitis B virus (HBV) genotypes in Egyptian pediatric cancer patients with acute and chronic active HBV infection  

Microsoft Academic Search

BACKGROUND: There are eight genotypes of hepatitis B virus (A-H) and subgenotypes are recognized. Genotyping can be accomplished based on a partial sequence of HBV genome such as the pre-S or S gene. Several methods have been developed and used for HBV genotyping. This study was undertaken to determine the HBV genotypes in Egyptian pediatric cancer patients with acute and

Abdel-Rahman N Zekri; Mohamed M Hafez; Nahed I Mohamed; Zeinab K Hassan; Manal H El-Sayed; Mohsen M Khaled; Tarek Mansour

2007-01-01

220

Configuration and replication competence of hepatitis B virus DNA in peripheral blood mononuclear cells from chronic hepatitis B patients and patients who have recovered from acute self-limited hepatitis  

Microsoft Academic Search

Several studies have reported the presence of hepatitis B virus (HBV) DNA in peripheral blood mononuclear cells (PBMCs). However, the mode of existence, infectivity and replication competence of HBV DNA in PBMCs remain unclear. To clarify these questions, we assayed for covalently closed circular DNA (cccDNA) and integrated HBV DNA in PBMCs from ten patients who had recovered from acute

Nobuyuki Torii; Kiyoshi Hasegawa; Riho Joh; Naoaki Hayashi

2003-01-01

221

Experimental non-alcoholic fatty liver disease results in decreased hepatic uptake transporter expression and function in rats  

PubMed Central

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of diagnoses ranging from simple fatty liver (SFL), to non-alcoholic steatohepatitis (NASH). This study aimed to determine the effect of moderate and severe NAFLD on hepatic transporter expression and function in vivo. Rats were fed a high-fat diet (SFL model) or a methionine-choline-deficient diet (NASH model) for eight weeks. Hepatic uptake transporter function was determined by bromosulfophthalein (BSP) disposition. Transporter expression was determined by branched DNA signal amplification assay and western blotting; inflammation was identified by immunostaining of liver slices for interleukin 1 beta (IL-1?). MC- rats showed significant retention of BSP in the plasma when compared to control rats. Hepatic NTCP, OATP1a1, 1a4, 1b2 and 2b1; and OAT 2 and 3 mRNA levels were significantly decreased in high-fat and MC- diet rats when compared to control. Protein expression of OATP1a1 was significantly decreased in high-fat animals, while OATP1a1 and OATP1b2 expression was significantly lower in MC- rats when compared to control. Liver tissue from high-fat and MC- rats stained positive for IL-1?, a pro-inflammatory cytokine known to decrease expression of NTCP, OATP and OAT transporters, suggesting a plausible mechanism for the observed transporter alterations. These data suggest that different stages of NAFLD result in altered hepatic uptake transporter expression that can lead to a functional impairment of xenobiotic uptake from the blood. Furthermore, NAFLD may alter the plasma retention time of clinically relevant drugs that are reliant on these transporters and may increase the potential drug toxicity. PMID:19358839

Fisher, Craig D.; Lickteig, Andrew J.; Augustine, Lisa M.; Oude Elferink, Ronald P.J.; Besselsen, David G.; Erickson, Robert P.; Cherrington, Nathan J.

2009-01-01

222

ACUTE EFFECT OF ETHANOL ON HEPATIC RETICULAR G6Pase AND Ca2+ POOL  

PubMed Central

Background Hydrolysis of glucose 6-phosphate via glucose 6-phosphatase enlarges the reticular Ca2+ pool of the hepatocyte. Exposure of liver cells to ethanol impairs reticular Ca2+ homeostasis. The present study investigated the effect of acute ethanol administration on glucose 6-phosphate supported Ca2+ accumulation in liver cells. Methods Total microsomes were isolated from rat livers acutely perfused with varying doses of ethanol (0.01%, 0.1%, or 1% v/v) for 8 minutes. Calcium uptake was assessed by 45Ca redistribution. Inorganic phosphate (Pi) formation was measured as an indicator of glucose 6-phosphatase hydrolytic activity. Results Glucose 6-phosphate-supported Ca2+ uptake decreased in a manner directly proportional to the dose of ethanol infused in the liver whereas Ca2+ uptake via SERCA pumps was decreased by ~25% only at the highest dose of alcohol administered. The reduced accumulation of Ca2+ within the microsomes resulted in a smaller IP3-induced Ca2+ release. Kinetic assessment of IP3 and passive Ca2+ release indicated a faster mobilization in microsomes from ethanol-treated livers, suggesting alcohol-induced alteration of Ca2+ releasing mechanisms. Pre-treatment of livers with chloromethiazole or dithio-threitol, but not 4-methyl-pyrazole prevented the inhibitory effect of ethanol on glucose 6-phosphatase activity and Ca2+ homeostasis. Conclusions Liver glucose 6-phosphatase activity and IP3-mediated Ca2+ release are rapidly inhibited following acute (8 min) exposure to ethanol, thus compromising the ability of the endoplasmic reticulum to dynamically modulate Ca2+ homeostasis in the hepatocyte. The protective effect of chloromethiazole and di-thio-threitol suggests that the inhibitory effect of ethanol is mediated through its metabolism via reticular cyP4502E1 and consequent free radicals formation. PMID:22958133

Jacobs-Harper, Amy; Crumbly, Ashlee; Romani, Andrea

2012-01-01

223

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

PubMed Central

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

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

2013-01-01

224

Acute abdomen as an unusual presentation of hepatic PEComa. A case report.  

PubMed

Perivascular epithelioid cell (PEC) tumors (or PEComas) are myomelanocytic lesions defined by coexpression of melanocytic and muscle markers, suggesting dual differentiation. They are rare mesenchymal tumors and include subtypes with distinct clinical features: angiomyolipoma, lymphangioleiomyomatosis, and clear cell "sugar" tumors of the lung, pancreas and uterus. Consequent upon the World Health Organization's recognition of PEC-derived tumors as a distinct entity, an increasing number of reports has documented PEComas arising at various anatomical locations. Clear cell myomelanocytic tumors of the falciform ligament/ligamentum teres (CCMTs) represent a rare variant of the PEComas. These hepatic PEComas, different from angiomyolipoma of the liver, pose a clinical, radiological and morphological diagnostic challenge. Because of their rarity, the clinical features and biological behavior of these tumors have yet to be established. We experienced our first case of CCMT in a 36-year-old woman who presented to our emergency department with a 3-day history of abdominal discomfort and progressive growth of an epigastric bulk. Intralesional hemorrhage was causing abdominal distension, which progressed to acute abdomen soon after. The hemoglobin concentration was 9.9 g/dL. Liver laboratory tests showed slight elevation of AST, ALT and gamma-GT. The alpha-fetoprotein level was not elevated. The radiological images showed a hemorrhagic mass with some bizarre features in left hepatic lobe, immediately adjacent to the ligamentum teres and falciform ligament. The patient underwent a left hepatic lobectomy. The diagnosis of CCMT was based on histological and immunohistochemical staining. The postoperative course was uneventful. The patient received no adjuvant treatment and is currently, 34 months after surgery, alive and disease free. In this report we describe a peculiar and hitherto undescribed clinical presentation of this tumor and its further course. Moreover, we discuss previously undescribed diagnostic imaging. We recommend that all unusual carcinomas and mesenchymal tumors of the liver should be tested for HMB-45: when positive, there is a high likelihood of PEComa. PMID:19366072

Priola, Adriano Massimiliano; Priola, Sandro Massimo; Cataldi, Aldo; Marci, Valerio; Fava, Cesare

2009-01-01

225

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

226

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

Tunon, Maria Jesus; Alvarez, Marcelino; Culebras, Jesus M; Gonzalez-Gallego, Javier

2009-01-01

227

Acute acetaminophen intoxication leads to hepatic iron loading by decreased hepcidin synthesis.  

PubMed

Acetaminophen (APAP), a major cause of acute liver injury in the Western world, is mediated by metabolism and oxidative stress. Recent studies have suggested a role for iron in potentiating APAP-induced liver injury although its regulatory mechanism is not completely understood. The current study was designed to unravel the iron-regulating pathways in mice after APAP-induced hepatotoxicity. Mice with severe injury showed a significant increase in liver iron concentration and oxidative stress. Concurrently, the plasma concentration of hepcidin, the key regulator in iron metabolism, and hepatic hepcidin antimicrobial peptide (Hamp) mRNA expression levels were significantly reduced. We showed that hepcidin transcription was inhibited via several hepcidin-regulating factors, including the bone morphogenetic protein/small mother against decapentaplegic (BMP/SMAD) pathway, CCAAT/enhancer-binding protein ? (C/EBP?), and possibly also via erythropoietin (EPO). Downregulation of the BMP/SMAD signaling pathway was most likely caused by hypoxia-inducible factor 1? (HIF-1?), which was increased in mice with severe APAP-induced liver injury. HIF-1? stimulates cleaving of hemojuvelin, the cofactor of the BMP receptor, thereby blocking BMP-induced signaling. In addition, gene expression levels of C/ebp? were significantly reduced, and Epo mRNA expression levels were significantly increased after APAP intoxication. These factors are regulated through HIF-1? during oxidative stress and suggest that HIF-1? is a key modulator in reduced hepcidin transcription after APAP-induced hepatotoxicity. In conclusion, acute APAP-induced liver injury leads to activation of HIF-1?, which results in a downregulation in hepcidin expression through a BMP/SMAD signaling pathway and through C/EBP? inhibition. Eventually, this leads to hepatic iron loading associated with APAP cytotoxicity. PMID:22610607

van Swelm, Rachel P L; Laarakkers, Coby M M; Blous, Linda; Peters, Janny G P; Blaney Davidson, Esmeralda N; van der Kraan, Peter M; Swinkels, Dorine W; Masereeuw, Rosalinde; Russel, Frans G M

2012-09-01

228

Dynamics of HCV RNA levels during acute hepatitis C virus infection.  

PubMed

Understanding viral dynamics during acute hepatitis C virus (HCV) infection can provide important insights into immunopathogenesis and guide early treatment. The aim of this study was to investigate the dynamics of HCV RNA and alanine transaminase (ALT) levels during recent HCV infection in the Australian Trial in Acute Hepatitis C (ATAHC). ATAHC was a prospective study of the natural history of recently acquired HCV infection. Longitudinal HCV RNA and ALT levels were compared among individuals with persistent infection and spontaneous clearance. Among those with HCV persistence (n?=?104) and HCV clearance (n?=?30), median HCV RNA (5.2 vs. 4.1?log?IU/ml, respectively) and ALT levels (779 vs. 1,765?IU/L, respectively) were high during month two following infection, and then declined during months three and four in both groups. Among those with HCV persistence, median HCV RNA was 2.9?log?IU/ml during months four, increased to 5.5?log?IU/ml during month five, and remained subsequently relatively stable. Among those with HCV clearance, median HCV RNA was undetectable by month five. Median HCV RNA levels were comparable between individuals with HCV persistence and HCV clearance during month three following infection (3.2 vs. 3.5?log?IU/ml, respectively; P?=?0.935), but markedly different during month five (5.5 vs. 1.0?log?IU/ml, respectively; P?

Hajarizadeh, Behzad; Grebely, Jason; Applegate, Tanya; Matthews, Gail V; Amin, Janaki; Petoumenos, Kathy; Hellard, Margaret; Rawlinson, William; Lloyd, Andrew; Kaldor, John; Dore, Gregory J

2014-10-01

229

Alcoholism.  

ERIC Educational Resources Information Center

This extensive annotated bibliography provides a compilation of documents retreived from a computerized search of the ERIC, Social Science Citation Index, and Med-Line databases on the topic of alcoholism. The materials address the following areas of concern: (1) attitudes toward alcohol users and abusers; (2) characteristics of alcoholics and…

Caliguri, Joseph P., Ed.

230

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 ...

231

Three male patients with sporadic acute hepatitis E in Sendai, Japan, who were domestically infected with hepatitis E virus of genotype III or IV.  

PubMed

Recent studies indicate that hepatitis E virus (HEV) infection occurs not only in developing countries but also in industrialized nations. However, the characteristics of domestic infections of hepatitis E in Japan are not fully understood. We analyzed serum samples from 34 patients who were seen at a city hospital in Sendai, Japan, between January 1997 and December 2002, and who had been given the diagnosis of sporadic acute hepatitis of non-A, non-B, non-C etiology. Among these 34 patients, 3 (9%; all men; aged 54, 59, and 61 years) were positive for both IgG and IgM anti-HEV antibodies and for HEV RNA. The HEV isolates (HE-JAS1 and HE-JAS3) obtained from case 1 and case 3, respectively, segregated into genotype III; they had the highest nucleotide sequence identity, of 99.5% and 99.0%, with HE-JA7 and HE-JA8, respectively, both of which had been isolated in Iwate, a neighboring prefecture of Sendai. In contrast, the remaining HEV isolate (HE-JAS2), obtained from case 2, segregated into genotype IV; it had the highest nucleotide sequence identity, of 99.8% and 99.3%, with JKK-Sap and HE-JA3, respectively, both of which had been isolated in Hokkaido, Japan, although case 2 had never been to Hokkaido. Our three patients with hepatitis E had not traveled abroad in the preceding 1 year, had had no contact with pigs, and no history of blood transfusion. These results indicate that HEV should be considered as an etiological agent of acute hepatitis of non-A, non-B, non-C etiology in Japan. The risk factor(s) for acquiring domestic HEV infection in Japan needs to be clarified in future studies. PMID:15065009

Yamamoto, Takeshi; Suzuki, Hiroshi; Toyota, Takayoshi; Takahashi, Masaharu; Okamoto, Hiroaki

2004-01-01

232

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

PubMed Central

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

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

2014-01-01

233

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

234

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

Microsoft Academic Search

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

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

1996-01-01

235

Ecological momentary assessment of acute alcohol use disorder symptoms: associations with mood, motives, and use on planned drinking days.  

PubMed

Several theories posit that alcohol is consumed both in relation to one's mood and in relation to different motives for drinking. However, there are mixed findings regarding the role of mood and motives in predicting drinking. Ecological momentary assessment (EMA) methods provide an opportunity to evaluate near real-time changes in mood and motives within individuals to predict alcohol use. In addition, endorsement of criteria of an alcohol use disorder (AUD) may also be sensitive to changes within subjects. The current study used EMA with 74 moderate drinkers who responded to fixed and random mood, motive, alcohol use, and AUD criteria prompts over a 21-day assessment period. A temporal pattern of daytime mood, evening drinking motivation, and nighttime alcohol use and acute AUD symptoms on planned drinking days was modeled to examine how these associations unfold throughout the day. The results suggest considerable heterogeneity in drinking motivation across drinking days. Additionally, an affect regulation model of drinking to cope with negative mood was observed. Specifically, on planned drinking days, the temporal association between daytime negative mood and the experience of acute AUD symptoms was mediated via coping motives and alcohol use. The current study found that motives are dynamic, and that changes in motives may predict differential drinking patterns across days. Further, the study provides evidence that emotion-regulation-driven alcohol involvement may need to be examined at the event level to fully capture the ebb and flow of negative affect motivated drinking. PMID:24932896

Dvorak, Robert D; Pearson, Matthew R; Day, Anne M

2014-08-01

236

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

237

Comprehensive treatment of acute-on-chronic liver failure in a patient with hepatitis B: a case report.  

PubMed

The clinical data of a patient with acute-on-chronic liver failure were analyzed retrospectively. The patient has suffered from hepatitis B for 30 years. His liver function deteriorated, yielding Child-Pugh grade C and reaching a model for end-stage liver disease score of 33 points within a short period; this condition was complicated with highly active variceal bleeding and coagulation system failure (PT > 100 s). The patient also presented hepatocellular carcinoma. Comprehensive treatments included effective inhibition of hepatitis B virus replication and intensive care support. Piggyback orthotopic liver transplantation was performed as the final treatment. The patient recovered uneventfully and was discharged after surgery. PMID:24810647

Li, Lei; Liu, Yimei; Luo, Tiancheng; Zhou, Jian; Hou, Yingyong; Shen, Xizhong; Wang, Jiyao

2014-06-01

238

Interactive effects of contextual cues and acute alcohol intoxication on the associations between alcohol expectancy activation and urge to drink.  

PubMed

This study examined the joint effects of contextual cues and alcohol intoxication on the associations between activation of positive and negative alcohol expectancies in memory and self-reported urges to drink alcohol after a laboratory alcohol administration. Young adult heavy drinkers were randomly assigned to drink a moderate dose of alcohol or a placebo (alcohol manipulation), and then listened to positive or negative drinking scenarios (cue manipulation). Before and after these manipulations, participants completed an alcohol expectancy Stroop task assessing positive and negative expectancy activation, as well as self-report measures of urges to drink. Regression analyses revealed that the alcohol and cue manipulations had a joint, moderating impact on the associations between expectancy activation and postcue changes in urge to drink. Specifically, both increased activation of negative expectancies and decreased activation of positive expectancies predicted decreases in urges to drink, but only for intoxicated participants in the negative cue condition. There were no associations between expectancy activation and urges to drink for those in the positive cue condition regardless of beverage condition. Results suggest that whether memory activation of alcohol expectancies has an impact on urge to drink after alcohol is on board may depend on the relevance of the activated expectancies to the current drinking context. This process appears to be influenced by a complex interaction between contextual cues in the environment and the pharmacological effects of alcohol. (PsycINFO Database Record (c) 2014 APA, all rights reserved). PMID:25111186

Wardell, Jeffrey D; Read, Jennifer P

2014-10-01

239

Acute delta superinfection in a previously unrecognised HBsAg carrier with transient loss of HBsAg simulating acute non-A, non-B hepatitis.  

PubMed Central

An 18 yr old previously well male Taiwanese was admitted with malaise, anorexia, and jaundice for two weeks. Results of liver tests were compatible with acute hepatitis. On day 1, he was seronegative for HBsAg, IgM anti-HAV, IgM anti-HBc, IgM anti-CMV, and IgM EBV capsid Ab, but positive for anti-delta in association with anti-HBc and anti-HBs. At follow up on day 5 HBsAg converted to positive with decreasing titre of anti-HBs. On day 19, the titre of HBsAg increased concomitantly with loss of anti-HBs. The results of these serological profiles indicated that this patient was a previously unrecognised HBsAg carrier, who developed acute hepatitis delta virus superinfection with transient loss of HBsAg. This phenomenon should be kept in mind in the serodiagnosis of acute viral hepatitis, especially in areas of high HBV prevalence. PMID:3135251

Chu, C M; Liaw, Y F

1988-01-01

240

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

241

Hepatic response to the oxidative stress induced by E. coli endotoxin: Glutathione as an index of the acute phase during the endotoxic shock  

Microsoft Academic Search

Reactive oxygen species are important mediators of cellular damage during endotoxic shock. In order to investigate the hepatic response to the oxidative stress induced by endotoxin, hepatic and plasma glutathione (total, GSH and GSSG), GSSG\\/GSH ratio as well as Mn-superoxide dismutase and catalase activities were determined during the acute and recovery phases of reversible endotoxic shock in the rat. A

M. Teresa Portolés; Myriam Catalfi; Adolfo Antón; Raffaella Pagani

1996-01-01

242

Poly(vinyl alcohol)-coated chitosan microparticles act as an effective oral vaccine delivery system for hepatitis B vaccine in rat model.  

PubMed

The present study focused on the development of an effective oral vaccine delivery system of poly(vinyl alcohol)-coated chitosan microparticles-based recombinant hepatitis B vaccine. Chitosan microparticles were prepared by ionotropic gelation technique; they were loaded with recombinant hepatitis B vaccine and coated with poly(vinyl alcohol). The average sizes of the microparticles were measured in the range of 100-410 nm. The optimal loading capacity and loading efficiency were recorded around 3.4 and 74%, respectively. In vitro release study shows that the prepared microparticles release the antigen in a sustained manner. Moreover, the microparticles were resistant to simulated gastric environment and release the antigen in the targeted intestinal milieu. Furthermore, oral immunisation of rats with poly(vinyl alcohol)-coated chitosan hepatitis-B microparticles vaccine shows comparable seroprotective immune response to presently practiced intramuscular vaccination. The results demonstrated that poly(vinyl alcohol)-coated chitosan microparticles have the potential for being used as an oral vaccine delivery system for hepatitis B vaccine and may be a suitable alternative for needle-based vaccination. PMID:25429498

Shrestha, Bijaya; Rath, Jyoti Prakash

2014-12-01

243

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

SciTech Connect

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

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

1988-01-01

244

A rare case of acute hepatitis induced by use of Babchi seeds as an Ayurvedic remedy for vitiligo.  

PubMed

This case highlights that hepatitis is a potential side effect of Babchi seeds, an Ayurvedic remedy used to treat vitiligo. The patient, a 52-year-old Indian woman, presented with a 1 week history of jaundice, vomiting, pruritus and abdominal pain. Progressive deterioration in liver function prompted a liver biopsy which was consistent with the diagnosis of a drug-induced hepatitis. The hepatitis resolved after withdrawal of its use. A PubMed search found no previous UK cases and only two cases have been reported globally. This potentially serious side effect of a widely available substance is not acknowledged by manufacturers, and those purchasing the product are unaware of the risk of harm. To compound this risk, there is an absence of dosing advice or maximum recommended daily intake. It is important to ask about topical and oral herbal remedies in cases of acute jaundice as patients rarely perceive these preparations as 'medications'. PMID:25103314

Smith, Deborah Ann; MacDonald, Stewart

2014-01-01

245

Selection for high alcohol preference drinking in mice results in heightened sensitivity and rapid development of acute functional tolerance to alcohol's ataxic effects.  

PubMed

Propensity to develop acute functional (or within session) tolerance to alcohol (ethanol) may influence the amount of alcohol consumed, with higher drinking associated with greater acute functional tolerance (AFT). The goal of this study was to assess this potential correlated response between alcohol preference and AFT in second and third replicate lines of mice selectively bred for high (HAP2 and HAP3) and low (LAP2 and LAP3) alcohol preference drinking. Male and female mice were tested for development of AFT on a static dowel task, which requires that animals maintain balance on a wooden dowel in order to prevent falling. On test day, each mouse received one (1.75 g/kg; Experiment 1) or two (1.75 and 2.0 g/kg; Experiment 2) injections of ethanol; an initial administration before being placed on the dowel and in Experiment 2, an additional administration after the first regain of balance on the dowel. Blood samples were taken immediately after loss of balance [when blood ethanol concentrations (BECs) were rising] and at recovery (during falling BECs) in Experiment 1, and after first and second recovery in Experiment 2. It was found that HAP mice fell from the dowel significantly earlier and at lower BECs than LAP mice following the initial injection of ethanol and were therefore more sensitive to its early effects. Furthermore, Experiment 1 detected significantly greater AFT development (BECfalling--BECrising) in HAP mice when compared with LAP mice, which occurred within ~30 min, supporting our hypothesis. However, AFT was not different between lines in Experiment 2, indicating that ~30-60 min following alcohol administration, AFT development was similar in both lines. These data show that high alcohol drinking genetically associates with both high initial sensitivity and very early tolerance to the ataxic effects of ethanol. PMID:22853703

Fritz, B M; Grahame, N J; Boehm, S L

2013-02-01

246

Scoring systems predict the prognosis of acute-on-chronic hepatitis B liver failure: an evidence-based review.  

PubMed

Acute-on-chronic hepatitis B liver failure is a devastating condition that is associated with mortality rates of over 50% and is consequent to acute exacerbation of chronic hepatitis B in patients with previously diagnosed or undiagnosed chronic liver disease. Liver transplantation is the definitive treatment to lower mortality rate, but there is a great imbalance between donation and potential recipients. An early and accurate prognostic system based on the integration of laboratory indicators, clinical events and some mathematic logistic equations is needed to optimize treatment for patients. As parts of the scoring systems, the MELD was the most common and the donor-MELD was the most innovative for patients on the waiting list for liver transplantation. This review aims to highlight the various features and prognostic capabilities of these scoring systems. PMID:24762209

Wu, Fa-Ling; Shi, Ke-Qing; Chen, Yong-Ping; Braddock, Martin; Zou, Hai; Zheng, Ming-Hua

2014-08-01

247

Hepatic abnormal perfusion visible by magnetic resonance imaging in acute pancreatitis  

PubMed Central

AIM: To study the prevalence and patterns of hepatic abnormal perfusion (HAP) visible by magnetic resonance imaging (MRI) in acute pancreatitis (AP). METHODS: Enhanced abdominal MRI was performed on 51 patients with AP. These patients were divided into two groups according to the MRI results: those with signs of gallstones, cholecystitis, common bile duct (CBD) stones or dilatation of the CBD on MRI and those without. The prevalence, shape and distribution of HAP in the two groups were analyzed and compared. The severity of AP was graded using the MR severity index (MRSI). The correlation between the MRSI and HAP was then analyzed. RESULTS: Of the 51 patients with AP, 32 (63%) showed at least one sign of gallbladder and CBD abnormalities on the MR images, while 19 (37%) showed no sign of gallbladder or CBD abnormalities. Nineteen patients (37%) had HAP visible in the enhanced images, including strip-, wedge- or patch-shaped HAP distributed in the hepatic tissue adjacent to the gallbladder and left and right liver lobes. There were no significant differences in the prevalence of HAP (?2 = 0.305, P = 0.581 > 0.05) or HAP distribution in the liver (?2 = 2.181, P = 0.536 > 0.05) between patients with and without gallbladder and CBD abnormalities. There were no significant differences in the MRSI score between patients with and without HAP (t = 0.559, P = 0.552 > 0.05). HAP was not correlated with the MRSI score. CONCLUSION: HAP is common in patients with AP and appears strip-, patch- or wedge-shaped on MRI. HAP on MRI cannot be used to indicate the severity of AP. PMID:24379936

Tang, Wei; Zhang, Xiao-Ming; Zhai, Zhao-Hua; Zeng, Nan-Lin

2013-01-01

248

Arousal effects of orexin A on acute alcohol intoxication-induced coma in rats.  

PubMed

The key role of the hypothalamic neuropeptides orexins in maintenance and promotion of arousal has been well established in normal mammalian animals, but whether orexins exert arousal effects under pathological condition such as coma was little studied. In this study, a model of unconscious rats induced by acute alcohol intoxication was used to examine the effects of orexins through intracerebroventricular injection. The results revealed that either orexin A or orexin B induced decrease of duration of loss of right reflex in alcohol-induced unconscious rats. In the presence of the selective orexin receptor 1 antagonist SB 334867 and orexin receptor 2 antagonist TCS OX2 29, the excitatory action of orexin A was completely blocked. Our data further presented that orexin A also induced reduction of delta power in EEG in these rats. Single-unit recording experiment in vivo demonstrated that orexin A could evoke increase of firing activity of prefrontal cortex neurons in unconscious rats. This excitation was completely inhibited by an H(1) receptor antagonist, pyrilamine, whereas application of ?(1)-adrenoreceptor antagonist prazosin or 5-HT(2) selective receptor antagonist ritanserin partially attenuated the excitatory effects of orexin A on these neurons. Consistently, the results of EEG recordings showed that microinjection of pyrilamine, prazosin, or ritanserin suppressed reduction of delta power in EEG induced by orexin A on unconscious rats. Thus, these data suggest that orexins exert arousal effects on alcohol-induced unconscious rats by the promotion of cortical activity through activation of histaminergic, noradrenergic and serotonergic systems. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. PMID:21924278

Jia, Xiaojun; Yan, Jie; Xia, Jianxia; Xiong, Jiaxiang; Wang, Tianhao; Chen, Yuan; Qi, Aiping; Yang, Nian; Fan, Shuangyi; Ye, Jianning; Hu, Zhian

2012-02-01

249

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

PubMed Central

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

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

2012-01-01

250

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

SciTech Connect

Purpose: This study was designed to determine the feasibility and efficacy of endovascular embolization with liquid embolic agent ethylene vinyl alcohol copolymer (Onyx) in patients with acute traumatic arterial bleeding. Methods: This is a retrospective review of 13 patients (9 men and 4 women; mean age 45 years) with severe trauma who underwent embolotherapy using Onyx from November 2003 to February 2009. Bleeding was located in the pelvis (5 patients), kidney (3 patients), mesenteric region (2 patients), retroperitoneal space (2 patients), neck (1 patient), and thigh (1 patient). In three cases (23.1%), Onyx was used in conjunction with coils. We evaluate the technical and clinical success, procedural and embolization time, occurrence of rebleeding, and embolotherapy-related complications, such as necrosis or migration of Onyx into nontarget vessels. Results: In all patients, embolotherapy was technically and clinically successful on the first attempt. Control of bleeding could be reached with a mean time of 19 (range, 4-63) min after correct placement of the microcatheter in the feeding artery. No recurrent bleeding was detected. No unintended necrosis or migration of Onyx into a nontarget region was observed. During the follow-up period, three patients (23.1%) died due to severe intracranial hemorrhage, cardiac arrest, and sepsis. Conclusions: Transcatheter embolization with new liquid embolic agent Onyx is technically feasible and effective in trauma patients with acute arterial hemorrhage.

Mueller-Wille, R., E-mail: rene.mueller-wille@klinik.uni-regensburg.de; Heiss, P., E-mail: peter.heiss@klinik.uni-regensburg.de [University Medical Center Regensburg, Department of Radiology (Germany); Herold, T., E-mail: thomas.herold@helios-kliniken.de [Helios Klinikum Berlin-Buch, Department of Radiology (Germany); Jung, E. M., E-mail: ernst-michael.jung@klinik.uni-regensburg.de; Schreyer, A. G., E-mail: andreas.schreyer@klinik.uni-regensburg.de; Hamer, O. W., E-mail: okka.hamer@klinik.uni-regensburg.de; Rennert, J., E-mail: janine.rennert@klinik.uni-regensburg.de; Hoffstetter, P., E-mail: P.hoffstetter@asklepios.com; Stroszczynski, C., E-mail: christian.stros@klinik.uni-regensburg.de [University Medical Center Regensburg, Department of Radiology (Germany); Zorger, N., E-mail: Niels.Zorger@barmherzige-regensburg.de [Krankenhaus Barmherzige Brueder Regensburg, Department of Radiology (Germany)

2012-02-15

251

Alcohol self-administration acutely stimulates the hypothalamic-pituitary-adrenal axis, but alcohol dependence leads to a dampened neuroendocrine state  

PubMed Central

Clinical studies link disruption of the neuroendocrine stress system with alcoholism, but remaining unknown is whether functional differences in the hypothalamic-pituitary-adrenal (HPA) axis precede alcohol abuse and dependence or result from chronic exposure to this drug. Using an operant self-administration animal model of alcohol dependence and serial blood sampling, we show that long-term exposure to alcohol causes significant impairment of HPA function in adult male Wistar rats. Acute alcohol (voluntary self-administration or experimenter-administered) stimulated the release of corticosterone and its upstream regulator, adrenocorticotropic hormone, but chronic exposure sufficient to produce dependence led to a dampened neuroendocrine state. HPA responses to alcohol were most robust in ‘low-responding’ non-dependent animals (averaging < 0.2 mg/kg/session), intermediate in non-dependent animals (averaging ~0.4 mg/kg/session), and most blunted in dependent animals (averaging ~1.0 mg/kg/session) following several weeks of daily 30-min self-administration sessions, suggesting that neuroendocrine tolerance can be initiated prior to dependence and relates to the amount of alcohol consumed. Decreased expression of corticotropin-releasing factor (CRF) mRNA expression in the paraventricular nucleus of the hypothalamus and reduced sensitivity of the pituitary to CRF may contribute to, but do not completely explain, neuroendocrine tolerance. The present results, combined with previous studies, suggest that multiple adaptations to stress regulatory systems may be brought about by excessive drinking, including a compromised hormonal response and a sensitized brain stress response that together contribute to dependence. PMID:18979677

Richardson, Heather N.; Lee, Soon Y.; O'Dell, Laura E.; Koob, George F.; Rivier, Catherine L.

2009-01-01

252

Alcoholism  

Microsoft Academic Search

Summary  Physicians can be most helpful to alcoholic patients, whatever the stage of progression of their illness, by adopting the\\u000a following strategies:\\u000a \\u000a \\u000a 1. \\u000a \\u000a Become familiar with the interactional dynamics that result from denial so as to improve data gathering and interpretation,\\u000a resulting in better diagnostic acumen. Expect to feel uncomfortable because of the interpersonal nature of alcoholism’s defenses.\\u000a Tolerate these feelings

Brian Johnson; William Clark

1989-01-01

253

Hepatitis  

MedlinePLUS

... fever, fatigue, lack of appetite, nausea, jaundice and dark urine.These symptoms can last up to five ... fever, fatigue, lack of appetite, nausea, jaundice and dark urine. Acute symptoms can last several months, during ...

254

Abdominal imaging can misdiagnose submassive hepatic necrosis as cirrhosis in acute liver failure.  

PubMed

Patients with acute liver failure (ALF) can be listed status I for liver transplantation (LT) whereas patients with cirrhosis must follow the MELD scoring system. Liver imaging can mistakenly diagnose submassive hepatic necrosis in ALF as cirrhosis. The purpose of our study was to assess the accuracy of ultrasound (US) and computed tomography (CT) in distinguishing cirrhosis from ALF. All patients listed for ALF and transplanted during the study period were included. Controls were age- and gender-matched cirrhotic patients who underwent LT during the same period. Abdominal US or CT scans obtained on all patients were independently reviewed by three blinded abdominal radiologists. Explants from all patients were reviewed by two blinded pathologists, and histological diagnosis was correlated with radiological diagnosis. Forty-one patients with ALF and 42 patients with cirrhosis were analyzed. Univariate and multivariate analyses both revealed overall accuracy of 85% for ultrasound and 93% for CT. US and CT scans both provide high levels of accuracy in terms of discriminating ALF from cirrhosis but measures taken to determine whether a patient has ALF vs. cirrhosis needs to approach 100% accuracy. Thus, imaging studies alone should not definitively diagnosis one etiology of liver failure over the other. PMID:23647426

Kim, Andrew I; Han, Steven-Huy; Tran, Doan-Trang; Sullivan, Peggy; Lassman, Charles; Raman, Steve; Zimmerman, Peter; Chin, Eva E

2013-01-01

255

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

256

Tenofovir as Rescue Therapy Following Clinical Failure to Lamivudine in Severe Acute Hepatitis B  

PubMed Central

Acute hepatitis B (AHB) is a self-limiting condition in more than 95% of cases. Treatment is however recommended in patients with severe AHB (<1% of cases), aiming to prevent liver failure and death. Various nucleos(t)ide analogues (NA) have been found to be effective in severe AHB, although NA-resistant strains causing AHB have been also recently reported. The use of tenofovir in severe AHB has only been described in 3 cases (1 adult and 1 infant with HBV mono-infection, 1 adult with HBV/HIV co-infection). We hereby report a 47-year-old treatment-naïve male, who developed severe AHB and was initially treated with lamivudine (LMV). Initial rapid biochemical response was followed by biochemical breakthrough after 9 days, suggesting LMV resistance. Rescue therapy with ‘add-on’ tenofovir brought about a sustained improvement in biochemical, serological and virological markers until HBsAg was lost after 4 months. Thus, this is the second adult HBV mono-infected patient, who responded successfully to tenofovir in severe AHB. PMID:23795273

Gerada, Jurgen; Borg, Elaine; Formosa, Denise; Magro, Rosalie; Pocock, James

2013-01-01

257

High Plasma Interleukin-18 Levels Mark the Acute Phase of Hepatitis C Virus Infection  

PubMed Central

Background.?Proinflammatory cytokines play a critical role in antiviral immune responses. Large-scale genome studies have found correlations between single-nucleotide polymorphisms (SNPs) in the interleukin (IL) 18 promoter and spontaneous control of hepatitis C virus (HCV), suggesting a role in clearance. Methods.?Plasma IL-18, IL-1?, IL-6, IL-8, IL-12, interferon-?, tumor necrosis factor–?, alanine aminotransferase (ALT), and HCV RNA levels were assessed longitudinally in subjects with known dates of HCV acquisition and analyzed according to IL-18 SNPs and outcome, either spontaneous clearance (SC) (n = 13) or persistent infection (PI) (n = 25). Results.?No significant change in plasma proinflammatory cytokine expression was observed with the exception of IL-18, which increased in every subject with initial detection of HCV RNA. In every SC subject, IL-18 returned to the preinfection baseline concomitant with HCV control. In PI subjects, IL-18 declined following the acute phase of infection but remained above the preinfection baseline throughout chronic infection and did not correlate with HCV RNA or ALT levels. Conclusions.?Plasma IL-18 was an early and the most reliably detected host response to HCV infection measured in blood. Reduced IL-18 production with transition to chronic infection without correlation with HCV RNA or ALT levels suggests modulation of the innate response with persistent infection. PMID:21984735

Chattergoon, Michael A.; Levine, Jordana S.; Latanich, Rachel; Osburn, William O.; Thomas, David L.

2011-01-01

258

Prostacyclin (PGI2) stabilises hepatic lysosomes during acute experimental pancreatitis in dogs.  

PubMed

In 15 mongrel dogs acute experimental pancreatitis (AEP) was induced by injection of bile and trypsin into the pancreatic duct. After 12 hrs in lysosomal enriched subfraction of the liver in untreated group (N = 5) relative free activity of cathepsins (Cs), acid phosphatase (AP) and beta-glucuronidase (beta G) increased to 50,62, and 53% respectively in comparison to the healthy dogs (N = 6) : 19,43 and 20%. In dogs with AEP treated with prostacyclin (PGI2) in the dose of 20 ng/kg X min for 12 hrs these activities of Cs, AP and beta G were lowered to 30,55 and 41% in comparison with the untreated group. In dogs with AEP (N = 5) additionally pretreated during 1 hr before the induction of AEP with the same rate of PGI2 i.v. infusion, the relative free activity of enzymes was similar to the treated group. After two hrs incubation of lysosomal enriched subfraction in acidic medium (pH = 5,0), the highest values of relative free activity were observed in untreated group, the difference being more pronounced in comparison with control group than before incubation. In those animals treated and pretreated with PGI2, postincubation activities were much lower than in untreated dogs. These results suggest the stabilising effect of PGI2 on hepatic lysosomes, damaged during the course of AEP in dogs. PMID:6753374

Dlugosz, J; Gabryelewicz, A; Andrzejewska, A; Triebling, A; Brzozowski, J; Wereszczynska, U

1982-07-01

259

False serologic evidence for acute primary toxoplasmosis during liver transplantation for fulminant hepatitis B: a case report.  

PubMed

Acute primary Toxoplasma gondii infection is usually considered to be a contraindication for solid organ transplantation. Recent reports of acute T. gondii infection have highlighted the need to include T. gondii serology in the pretransplant screening of solid-organ transplant recipients. However such serology might be misleading. We describe the case of a 25-year-old woman who received a liver transplantation for life-threatening liver failure due to hepatitis B virus infection. The presence of high IgM titers against T. gondii, as detected by membrane immunoassay, immunofluorescence, and mu-capture ELISA tests, together with the absence of IgG antibodies in the immediate pretransplant serology screening suggested acute primary T. gondii infection at the time of transplantation. We initiated a preemptive therapy with intravenous clindamycin and cotrimoxazole. However, negative PCR and IgA capture assays, together with the absence of a sustained IgG response finally excluded the initial diagnosis of primary toxoplasmosis, leading to discontinuation of antitoxoplasmosis therapy. This case illustrates the problem that, in the context of fulminant hepatitis B, serologic markers for acute primary toxoplasmosis can be falsely positive. Confirmation by PCR and IgA antibody determinations is required to confirm this diagnosis. PMID:20005415

Uçkay, I; Wunderli, W; Giostra, E; Majno, P; Mentha, G; van Delden, C

2009-12-01

260

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

261

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

Microsoft Academic Search

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

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

2010-01-01

262

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

263

Effect of alcohol on hepatic receptor of high density lipoproteins (HDL)  

SciTech Connect

Moderate alcohol intake has been shown to increase HDL cholesterol and proteins. The seemingly protective effect' of moderate alcohol drinking against cardiovascular diseases has been attributed to an increase in serum HDL. In this study, the authors show that a receptor for HDL is present in rat liver. Rat liver membrane was prepared by stepwise ultracentrifugation. Apo Al was iodinated using {sup 125}I-NaI and IODO-beads. HDL was labeled by incubating with {sup 125}I-apo Al then refloated be centrifugation. Binding of {sup 125}I-HDL to rat liver membrane reached equilibrium by 2-3 h and was saturable at 37C. The binding was inhibited 80% by excess unlabeled HDL, but was inhibited only 25% by excess LDL. It could also be inhibited by preincubating HDL with anti-apo Al or anti-apo E antisera but not with anti-apo AIV or control sera. The binding affinity of HDL to the liver membrane of rats fed alcohol for 5 wk was 50% that of their pair-fed controls. Thus a decrease in the binding of HDL to liver membrane due to alcohol-drinking may result in a slower clearance of HDL by the liver and consequently a higher HDL concentration in the serum.

Lin, R.C.; Miller, B.M. (Indiana Univ., Indianapolis (United States) V.A. Medical Center, Indianapolis, IN (United States))

1991-03-11

264

Integration and proliferation of transplanted cells in hepatic parenchyma following D-galactosamine-induced acute injury in F344 rats.  

PubMed

To determine whether liver repopulation with cell transplantation could be of therapeutic value in acute hepatic failure, it is necessary to establish the fate of transplanted hepatocytes. This study used dipeptidyl peptidase IV-deficient F344 rats as recipients to analyse the engraftment and proliferation of transplanted hepatocytes. Syngeneic hepatocytes were transplanted intrasplenically 24-30 h after induction of liver injury by D-galactosamine (GalN). Portosystemic shunting was analysed with 99m-Tc-labelled albumin microspheres. GalN-treated rats showed characteristic hepatic necrosis, inflammation, gamma-glutamyl transpeptidase activation, and regenerative activity, without increased portosystemic shunting (>99% 99m-Tc activity was in the liver in normal and GalN-treated rats). Transplanted cells entered hepatic sinusoids promptly and were observed in liver plates at 48 h. The number of transplanted cells increased in GalN-treated rats by approximately seven-fold (range two- to 12-fold), along with evidence for DNA synthesis between 3 and 14 days after cell transplantation and greater prevalence of larger transplanted cell clusters. These findings indicate that the liver can be safely repopulated in animals with acute liver failure, although the time required for regenesis of plasma membrane structures and proliferation in transplanted hepatocytes will need to be considered in developing therapeutic strategies. PMID:10657020

Gupta, S; Rajvanshi, P; Irani, A N; Palestro, C J; Bhargava, K K

2000-02-01

265

Acute cold- and chronic heat-exposure upregulate hepatic leptin and muscle uncoupling protein (UCP) gene expression in broiler chickens.  

PubMed

Emerging evidence showed that variations in environmental temperature affect both leptin and uncoupling protein (UCP) gene expression in mammals, whereas a little is known about such interactions in birds. Thus, we conducted the present study to investigate the influence of acute (2 hours) cold (4 degrees C) and chronic (10 days) heat (32 degrees C) exposure on hepatic leptin and muscle UCP gene expression in 5-wk-old broiler chickens. Both cold- and heat-exposure significantly (P < 0.05 to P < 0.001) upregulated hepatic leptin (by 35 and 46%, respectively) and muscle UCP mRNA levels (by 71 and 71%, respectively) compared to the thermoneutrality (22 degrees C). This result suggests that leptin and UCP may be involved in the thermoregulation response of chickens to extreme climate (cold and hot temperatures). The upregulation of hepatic leptin gene expression was accompanied by an increase in plasma leptin levels, indicating that leptin may be regulated at transcriptional level. The increase of leptin and UCP mRNA abundance, and leptinemia we report here were not related to plasma glucose or insulin levels. In conclusion, the exposure of broiler chickens to extreme ambient temperatures (cold and heat) increases hepatic leptin and muscle UCP gene expression. PMID:18473347

Dridi, Sami; Temim, Soraya; Derouet, Michel; Tesseraud, Sophie; Taouis, Mohammed

2008-08-01

266

Effect of Carrageenan-induced Acute Peripheral Inflammation on the Pharmacokinetics and Hepatic Metabolism of Midazolam in Rats.  

PubMed

The effect of carrageenan-induced acute peripheral inflammation (API) on the pharmacokinetics of the hepatically metabolizing compound midazolam (MDZ) was investigated in rats. Rats were subcutaneously treated with ?-carrageenan in the hind paw to induce API. When MDZ was intravenously administered in male rats, it was demonstrated that the plasma concentration profile of MDZ slightly alters in API rats compared with that in normal rats, while the plasma concentrations of its metabolites, 4-hydroxy and 1'-hydroxy MDZ, are markedly reduced with delayed appearances in API rats. In the incubation study with rat liver microsomes, it was clearly indicated that the generation rates of the two metabolites decrease in API rats. Western blot analysis revealed that hepatic CYP3A1 expression increases, while CYP3A2 expression decreases in API rats. In female rats, in which CYP3A2 is barely expressed in the liver, MDZ metabolism is little affected by API. These findings indicate that the hepatic handling of a therapeutic compound varies with API, largely due to altered hepatic expression of the drug-metabolizing enzyme. PMID:24717840

Kajikawa, Noriko; Doi, Masami; Kusaba, Jun-Ichi; Aiba, Tetsuya

2014-10-25

267

Anti-inflammatory activity of alcoholic extract of Adenema hyssopifolium G.Don in acute and chronic experimental models in albino rats  

Microsoft Academic Search

Objective: To evaluate the anti-inflammatory effect of alcoholic extract of Adenema hyssopifolium. Methodology and results: Carrageen induced rat paw edema method (acute), Turpentine oil induced granuloma pouch (sub acute) and formalin induced rat hind paw edema (chronic) models in rats was adopted for the study. The alcohol extract (using 90%) at a concentration of 300 and 600 mg kg-1 p.o.,

R. Arivukkarasu; A. Rajasekaran; S. Murugesh

268

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

SciTech Connect

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

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

1995-12-31

269

The protective effects of carnosine in alcohol-induced hepatic injury in rats.  

PubMed

Consumption of alcohol leads to oxidative stress in liver by inducing lipid peroxidation. The aim of this study was to investigate the effects of carnosine (CAR) in alcohol-induced liver injury by biochemical and histomorphological evaluations. The rats were divided into four groups, namely, control group, alcohol (AL) group, CAR group and AL + CAR group. Three doses of ethanol (5 g/kg, 25% (v/v) in distilled water) were given by nasogastric catheter for twice-a-day. CAR (100 mg/kg) was given 1 h before the administration of ethanol using the same method. Levels of alanine aminotransferase, aspartate aminotransferase, myeloperoxidase and malondialdehyde were significantly increased in the AL group compared with control, CAR and AL + CAR groups. Glutathione level was significantly decreased in the AL group, while it was increased in the AL + CAR group. Immunoreactivity of caspase-3 and bax increased in the hepatocytes of AL group when compared with control and AL + CAR groups. Expression of bcl-2 was decreased in AL group than AL + CAR group. Under electron microscopy, dense mitochondria, accumulation of lipid, sinusoidal dilatation, vacuolization and decrease in the number of microvilli were observed in AL group, while these findings were markedly less in the AL + CAR group. In conclusion, pretreatment of CAR is effective for recovering biochemical alterations and morphologic damage in the liver of rats treated with ethanol. PMID:22661399

Baykara, B; Micili, S Cilaker; Tugyan, K; Tekmen, I; Bagriyanik, Ha; Sonmez, U; Sonmez, A; Oktay, G; Yener, N; Ozbal, S

2014-02-01

270

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

271

Exenatide decreases hepatic fibroblast growth factor 21 resistance in non-alcoholic fatty liver disease in a mouse model of obesity and in a randomised controlled trial  

PubMed Central

Aims/hypothesis Systemic fibroblast growth factor (FGF)21 levels and hepatic FGF21 production are increased in non-alcoholic fatty liver disease patients, suggesting FGF21 resistance. We examined the effects of exenatide on FGF21 in patients with type 2 diabetes and in a diet-induced mouse model of obesity (DIO). Methods Type 2 diabetes mellitus patients (n=24) on diet and/or metformin were randomised (using a table of random numbers) to receive additional treatment consisting of pioglitazone 45 mg/day or combined therapy with pioglitazone (45 mg/day) and exenatide (10 ?g twice daily) for 12 months in an open label parallel study at the Baylor Clinic. Results Twenty-one patients completed the entire study and were included in the analysis. Pioglitazone treatment (n=10) reduced hepatic fat as assessed by magnetic resonance spectroscopy, despite a significant increase in body weight (?=3.7 kg); plasma FGF21 levels did not change (1.9±0.6 to 2.2±0.6 ng/ml [mean±SEM]). However, combined pioglitazone and exenatide therapy (n=11) was associated with a significant reduction of FGF21 levels (2.3±0.5 to 1.1± 0.3 ng/ml) and a greater decrease in hepatic fat. Besides weight gain observed in the pioglitazone-treated patients, lower extremity oedema was observed as a side effect in two of the ten patients. Three patients who received pioglitazone and exenatide combination therapy complained of significant nausea that was self-limiting and did not require them to leave the study. In DIO mice, exendin-4 for 4 weeks significantly reduced hepatic triacylglycerol content, decreased hepatic FGF21 protein and mRNA, and enhanced phosphorylation of hepatic AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, although no significant difference in weight and body fat was observed. Hepatic FGF21 correlated inversely with hepatic AMPK phosphorylation Conclusions/interpretation In type 2 diabetes mellitus, combined pioglitazone and exenatide therapy is associated with a reduction in plasma FGF21 levels, as well as a greater decrease in hepatic fat than that achieved with pioglitazone therapy. In DIO mice, exendin-4 treatment reduces hepatic triacylglycerol and FGF21 protein, and enhances hepatic AMPK phosphorylation, suggesting an improvement of hepatic FGF21 resistance. PMID:21956711

Samson, S. L.; Sathyanarayana, P.; Jogi, M.; Gonzalez, E. V.; Gutierrez, A.; Krishnamurthy, R.; Muthupillai, R.; Chan, L.

2013-01-01

272

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

273

Acute disinhibiting effects of alcohol as a factor in risky driving behavior  

Microsoft Academic Search

Automobile crash reports show that up to 40% of fatal crashes in the United States involve alcohol and that younger drivers are over-represented. Alcohol use among young drivers is associated with impulsive and risky driving behaviors, such as speeding, which could contribute to their over-representation in alcohol-related crash statistics. Recent laboratory studies show that alcohol increases impulsive behaviors by impairing

Mark T. Fillmore; Jaime S. Blackburn; Emily L. R. Harrison

2008-01-01

274

Acute hepatic ischemic-reperfusion injury induces a renal cortical "stress response," renal "cytoresistance," and an endotoxin hyperresponsive state.  

PubMed

Hepatic ischemic-reperfusion injury (HIRI) is considered a risk factor for clinical acute kidney injury (AKI). However, HIRI's impact on renal tubular cell homeostasis and subsequent injury responses remain ill-defined. To explore this issue, 30-45 min of partial HIRI was induced in CD-1 mice. Sham-operated or normal mice served as controls. Renal changes and superimposed injury responses (glycerol-induced AKI; endotoxemia) were assessed 2-18 h later. HIRI induced mild azotemia (blood urea nitrogen ?45 mg/dl) in the absence of renal histologic injury or proteinuria, implying a "prerenal" state. However, marked renal cortical, and isolated proximal tubule, cytoprotective "stress protein" gene induction (neutrophil gelatinase-associated lipocalin, heme oxygenase-1, hemopexin, hepcidin), and increased Toll-like receptor 4 (TLR4) expression resulted (protein/mRNA levels). Ischemia caused release of hepatic heme-based proteins (e.g., cytochrome c) into the circulation. This corresponded with renal cortical oxidant stress (malondialdehyde increases). That hepatic derived factors can evoke redox-sensitive "stress protein" induction was implied by the following: peritoneal dialysate from HIRI mice, soluble hepatic extract, or exogenous cytochrome c each induced the above stress protein(s) either in vivo or in cultured tubule cells. Functional significance of HIRI-induced renal "preconditioning" was indicated by the following: 1) HIRI conferred virtually complete morphologic protection against glycerol-induced AKI (in the absence of hyperbilirubinemia) and 2) HIRI-induced TLR4 upregulation led to a renal endotoxin hyperresponsive state (excess TNF-?/MCP-1 gene induction). In conclusion, HIRI can evoke "renal preconditioning," likely due, in part, to hepatic release of pro-oxidant factors (e.g., cytochrome c) into the systemic circulation. The resulting renal changes can impact subsequent AKI susceptibility and TLR4 pathway-mediated stress. PMID:25080526

Zager, Richard A; Johnson, Ali C M; Frostad, Kirsten B

2014-10-01

275

A fatal case of acute hepatitis E among pregnant women, Central African Republic  

Microsoft Academic Search

BACKGROUND: Hepatitis E virus (HEV) is a major public health problem in developing countries. HEV infection in pregnant women is more common and more often fatal in the third trimester. The mortality rate due to HEV-induced hepatitis is as high as 15-20 per cent. The present study was designed to determine the potential factors responsible for high mortality rate among

Charles M Goumba; Emmanuel R Yandoko-Nakouné; Narcisse P Komas

2010-01-01

276

Epidemiological characteristics and medical follow-up of 61 patients with acute hepatitis C identified through the hepatitis C surveillance system in France  

PubMed Central

SUMMARY This study aimed to describe current epidemiological and clinical characteristics, medical follow-up and outcome in the real practice of acute hepatitis C (AHC) patients. AHC cases were retrospectively identified through the French Hepatology Reference Centres Surveillance system and additional data were collected. Sixty-one patients with AHC were identified (sex ratio: M/F 1·7/1; mean age 39 years). Forty-four (72%) had documented seroconversion within a 6-month period. Main reported risk exposures were intravenous or nasal drug use (35%), invasive medical procedures (25%) and sexual contact with a HCV-positive partner (20%). Spontaneous clearance of HCV RNA was observed in seven out of 16 patients followed without therapy. This study confirms the major role of drug use in HCV transmission and highlights the role of invasive medical procedures and occupational exposure. PMID:17697444

BROUARD, C.; PRADAT, P.; DELAROCQUE-ASTAGNEAU, E.; SILVAIN, C.

2008-01-01

277

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

278

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

279

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

280

Citric acid reduces the decline in P300 amplitude induced by acute alcohol consumption in healthy adults*  

PubMed Central

Event-related potential (ERP) is a reliable neuroelectric measure of brain activity that helps to confirm the assessment of mental status and cognitive impairment. Many studies have reported that alcoholics show a significantly lower ERP P300 amplitude than the norm. In the present study, ERP P300 waves were measured to evaluate the effect of citric acid on cognitive function during excessive alcohol consumption in healthy adults. Five volunteers were selected through clinical interview, physical examination, and psychiatric assessment for participation in this study. In a double-blind placebo-controlled before-after design, each subject was treated with 5 ml/kg body weight alcohol, 5 ml/kg body weight alcohol and 1 mg citric acid, or a placebo on three separate occasions, one week apart. ERP P300, blood biochemical indicators, blood alcohol concentrations (BACs) and acetaldehyde concentrations were assessed. Repeated measure analysis of variance (ANOVA) with a within-subjects factor was used to evaluate differences in blood biochemical indicators, BACs, blood acetaldehyde concentrations, and ERP P300 in the three sessions of assessments. Several blood biochemical indicators showed significant differences between treatments, including the levels of cholinesterase (CHE), total bile acid (TBA), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and glycylproline dipeptidyl aminopeptidase (GPDA). BACs after consumption of alcohol alone or citric acid with alcohol were significantly higher compared to those after placebo treatment (P<0.05). There were no significant differences in blood acetaldehyde concentrations between the treatments. The P300 amplitudes on the frontal (Fz), central (Cz), and parietal (Pz) regions of the scalp after consumption of alcohol were significantly lower than those after consumption of the placebo or citric acid with alcohol (P<0.05), while there were no significant differences between the latter two treatments. The results of this study suggest that citric acid could reduce the decline in ERP P300 amplitude and cognitive ability induced by acute alcohol consumption. It may also affect some blood biochemical indicators, but the specific mechanisms need further research. PMID:22556178

Chen, Wei-xing; Xu, Chuan-qin; Chen, Shao-hua; Xu, Gen-yun; Ye, Huai-zhuang

2012-01-01

281

A prospective study of the influence of acute alcohol intoxication versus chronic alcohol consumption on outcome following traumatic brain injury.  

PubMed

The purpose of the study was to disentangle the relative contributions of day-of-injury alcohol intoxication and pre-injury alcohol misuse on outcome from TBI. Participants were 142 patients enrolled from a Level 1 Trauma Center (in Vancouver, Canada) following a traumatic brain injury (TBI; 43 uncomplicated mild TBI and 63 complicated mild-severe TBI) or orthopedic injury [36 trauma controls (TC)]. At 6-8 weeks post-injury, diffusion tensor imaging (DTI) of the whole brain was undertaken using a Phillips 3T scanner. Participants also completed neuropsychological testing, an evaluation of lifetime alcohol consumption (LAC), and had blood alcohol levels (BALs) taken at the time of injury. Participants in the uncomplicated mild TBI and complicated mild-severe TBI groups had higher scores on measures of depression and postconcussion symptoms (d = 0.45-0.83), but not anxiety, compared with the TC group. The complicated mild-severe TBI group had more areas of abnormal white matter on DTI measures (all p < .05; d = 0.54-0.61) than the TC group. There were no difference between groups on all neurocognitive measures. Using hierarchical regression analyses and generalized linear modeling, LAC and BAL did provide a unique contribution toward the prediction of attention and executive functioning abilities; however, the variance accounted for was small. LAC and BAL did not provide a unique and meaningful contribution toward the prediction of self-reported symptoms, DTI measures, or the majority of neurocognitive measures. In this study, BAL and LAC were not predictive of mental health symptoms, postconcussion symptoms, cognition, or white-matter changes at 6-8 weeks following TBI. PMID:24964748

Lange, Rael T; Shewchuk, Jason R; Rauscher, Alexander; Jarrett, Michael; Heran, Manraj K S; Brubacher, Jeffrey R; Iverson, Grant L

2014-08-01

282

Surveillance for Viral Hepatitis - United States, 2012  

MedlinePLUS

... PPTX - 832KB] Hepatitis B virus PAGE DESCRIPTION Table 3.1 Reported cases of acute hepatitis B, by state ? ... characteristic and year – United States, 2007-2011 Slide 3.1 Reported number of acute hepatitis B cases — United ...

283

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

284

Shift of hepatitis E virus RNA from hepatocytes to biliary epithelial cells during acute infection of rhesus monkey.  

PubMed

Hepatitis E virus (HEV) has been considered to be the major cause of enterically transmitted non-A, non-B hepatitis in developing countries. However, little is known about viral replication and localization in the liver. The aim of this study was to examine the distribution of HEV-infected cells in experimentally infected animals. Seven captured wild rhesus monkeys were inoculated intravenously with faecal extract derived from a Myanmar strain of HEV. Animals were killed at different time-points of clinical illness: during early infection, during prehepatitis with viral-like particles in bile, during acute hepatitis and during convalescence. Intrahepatic localization of HEV was analysed using non-isotopic thymine dimer in situ hybridization (NITDISH). Both plus and minus strands of HEV RNA were found in hepatocytes during the early infection period. Staining in the submembranous cytoplasmic region of hepatocytes was observed. In the prehepatitis period, both plus and minus strand HEV RNAs appeared in the canalicular side of isolated bile epithelial cells. Subsequently, HEV RNA became universally distributed in the cytoplasm of medium-size bile epithelial cells. After recovery, HEV RNA disappeared. PMID:10607243

Kawai, H F; Koji, T; Iida, F; Kaneko, S; Kobayashi, K; Nakane, P K

1999-07-01

285

Gentiana manshurica Kitagawa prevents acetaminophen-induced acute hepatic injury in mice via inhibiting JNK/ERK MAPK pathway  

PubMed Central

AIM: To investigate the in vivo hepatoprotective effects and mechanisms of Gentiana manshurica Kitagawa (GM) in acetaminophen (APAP)-induced liver injury in mice. METHODS: GM (200, 150 or 50 mg/kg body weight) or N-acetyl-L-cysteine (NAC; 300 mg/kg body weight) was administrated orally with a single dose 2 h prior to APAP (300 mg/kg body weight) injection in mice. RESULTS: APAP treatment significantly depleted hepatic glutathione (GSH), increased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and malonyldialdehyde (MDA) and 4-hydroxynonenal levels, and decreased hepatic activity of glutathione peroxidase (GSH-px) and superoxide dismutase (SOD). However, the pretreatment of GM significantly alleviated APAP-induced oxidative stress by increasing GSH content, decreasing serum ALT, AST and MDA, and retaining the activity of GSH-px and SOD in the liver. Furthermore, GM pretreatment can inhibit caspase-3 activation and phosphorylation of c-Jun-NH2-terminal protein kinase 2 (JNK1/2) and extracellular signal-regulated kinase (ERK). GM also remarkably attenuated hepatocyte apoptosis confirmed by the terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling method. CONCLUSION: Hepatoprotective effects of GM against APAP-induced acute toxicity are mediated either by preventing the decline of hepatic antioxidant status or its direct anti-apoptosis capacity. These results support that GM is a potent hepatoprotective agent. PMID:20082487

Wang, Ai-Yan; Lian, Li-Hua; Jiang, Ying-Zi; Wu, Yan-Ling; Nan, Ji-Xing

2010-01-01

286

Identification of Hepatic Niche Harboring Human Acute Lymphoblastic Leukemic Cells via the SDF-1/CXCR4 Axis  

PubMed Central

In acute lymphoblastic leukemia (ALL) patients, the bone marrow niche is widely known to be an important element of treatment response and relapse. Furthermore, a characteristic liver pathology observed in ALL patients implies that the hepatic microenvironment provides an extramedullary niche for leukemic cells. However, it remains unclear whether the liver actually provides a specific niche. The mechanism underlying this pathology is also poorly understood. Here, to answer these questions, we reconstituted the histopathology of leukemic liver by using patients-derived primary ALL cells into NOD/SCID/Yc null mice. The liver pathology in this model was similar to that observed in the patients. By using this model, we clearly demonstrated that bile duct epithelial cells form a hepatic niche that supports infiltration and proliferation of ALL cells in the liver. Furthermore, we showed that functions of the niche are maintained by the SDF-1/CXCR4 axis, proposing a novel therapeutic approach targeting the extramedullary niche by inhibition of the SDF-1/CXCR4 axis. In conclusion, we demonstrated that the liver dissemination of leukemia is not due to nonselective infiltration, but rather systematic invasion and proliferation of leukemic cells in hepatic niche. Although the contribution of SDF-1/CXCR4 axis is reported in some cancer cells or leukemic niches such as bone marrow, we demonstrated that this axis works even in the extramedullary niche of leukemic cells. Our findings form the basis for therapeutic approaches that target the extramedullary niche by inhibiting the SDF-1/CXCR4 axis. PMID:22069486

Kato, Itaru; Niwa, Akira; Heike, Toshio; Fujino, Hisanori; Saito, Megumu K.; Umeda, Katsutsugu; Hiramatsu, Hidefumi; Ito, Mamoru; Morita, Makiko; Nishinaka, Yoko; Adachi, Souichi; Ishikawa, Fumihiko; Nakahata, Tatsutoshi

2011-01-01

287

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.; Kaplan, Mark S.

2013-01-01

288

Hepatitis B virus (HBV) genotypes in Egyptian pediatric cancer patients with acute and chronic active HBV infection  

PubMed Central

Background There are eight genotypes of hepatitis B virus (A-H) and subgenotypes are recognized. Genotyping can be accomplished based on a partial sequence of HBV genome such as the pre-S or S gene. Several methods have been developed and used for HBV genotyping. This study was undertaken to determine the HBV genotypes in Egyptian pediatric cancer patients with acute and chronic liver disease. Methods HBV genotypes were determined in 22 patients who had acute forms of liver disease (AH) and in 48 patients with chronic active hepatitis (CAH). A type-specific primer based the nested-PCR method was employed in the HBV genotyping. Results This study showed that HBV infections in pediatric cancer patients are attributed predominantly to viral genotypes D and B that constituted 37.1% and 25.7%, respectively of the total infections. In addition, there was a relatively high prevalence of mixed infections of 15.7% among the studied group especially mixed A/D genotype infections. Genotype D was found significantly more often in patients with CAH than in patients with AH [23/48(47.9%) v 3/22 (13.6%)]. Conclusion These findings show the distribution of HBV A-D genotypes in pediatric cancer Egyptian patients. Furthermore, our results indicate a markedly high prevalence of mixed A/D genotype infections in subjects with CAH and a possible association of mixed infections with the severity of liver diseases. PMID:17631684

Zekri, Abdel-Rahman N; Hafez, Mohamed M; Mohamed, Nahed I; Hassan, Zeinab K; El-Sayed, Manal H; Khaled, Mohsen M; Mansour, Tarek

2007-01-01

289

Protective Effect of Baccharis trimera Extract on Acute Hepatic Injury in a Model of Inflammation Induced by Acetaminophen  

PubMed Central

Background. Acetaminophen (APAP) is a commonly used analgesic and antipyretic. When administered in high doses, APAP is a clinical problem in the US and Europe, often resulting in severe liver injury and potentially acute liver failure. Studies have demonstrated that antioxidants and anti-inflammatory agents effectively protect against the acute hepatotoxicity induced by APAP overdose. Methods. The present study attempted to investigate the protective effect of B. trimera against APAP-induced hepatic damage in rats. The liver-function markers ALT and AST, biomarkers of oxidative stress, antioxidant parameters, and histopathological changes were examined. Results. The pretreatment with B. trimera attenuated serum activities of ALT and AST that were enhanced by administration of APAP. Furthermore, pretreatment with the extract decreases the activity of the enzyme SOD and increases the activity of catalase and the concentration of total glutathione. Histopathological analysis confirmed the alleviation of liver damage and reduced lesions caused by APAP. Conclusions. The hepatoprotective action of B. trimera extract may rely on its effect on reducing the oxidative stress caused by APAP-induced hepatic damage in a rat model. General Significance. These results make the extract of B. trimera a potential candidate drug capable of protecting the liver against damage caused by APAP overdose.

Pádua, Bruno da Cruz; Rossoni Júnior, Joamyr Victor; de Brito Magalhães, Cíntia Lopes; Chaves, Míriam Martins; Silva, Marcelo Eustáquio; Pedrosa, Maria Lucia; de Souza, Gustavo Henrique Bianco; Brandão, Geraldo Célio; Rodrigues, Ivanildes Vasconcelos; Lima, Wanderson Geraldo; Costa, Daniela Caldeira

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

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

PubMed

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

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

2014-10-01

292

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

293

Tissue Localization of Australia Antigen Immune Complexes in Acute and Chronic Hepatitis and Liver Cirrhosis  

PubMed Central

In a significant percentage of examined cases of fulminant hepatitis, subacute hepatitis, chronic aggressive hepatitis, liver cirrhosis and chronic persistent hepatitis, Australia (hepatitis-associated) antigen (Au HAA) was identified in the liver and in extrahepatic locations. The several immunofluorescent patterns of Au HAA localization in hepatocytes strongly suggested various stages of Au HAA accumulation and release. Deposits of a mixture of immunoglobulins G and M and occasionally ?1C-globulin were found in the cytoplasm of Au HAA containing hepatocytes, on their plasma membranes, on or in the nuclei, in the cytoplasm of Kupffer cells and, rarely, in the sinusoids. The accompanying tissue changes were hepatocellular degeneration and necrosis. These intra- and extracellular complexes of Au HAA and immunoglobulins displayed strong affinity for guinea pig complement in the immunohistochemical complement fixation reaction. When tested by immunodiffusion in agar, IgG dissociated from these complexes by potassium thiocyanate (KSCN) treatment showed anti-Au HAA specificity. In fulminant hepatitis neither Au HAA nor immunoglobulins and complement were found in the liver. In chronic aggressive hepatitis and subacute hepatitis the amount of the Au HAA immune complexes identified in the liver was approximately inversely proportional to the extent and severity of the parenchymal lesions. In liver cirrhosis and chronic persistent hepatitis there was a positive correlation between the amount of the Au HAA immune complexes found in the liver and the degree of hepatocellular damage. The deposits of Au HAA, identified in extrahepatic locations including germinal centers of lymph nodes and spleen, kidney glomeruli and blood vessel walls, were as a rule accompanied by deposits of IgG, IgM, ?1C-globulin and fibrin. All these deposits showed strong affinity for guinea pig complement in the immunohistochemical reaction of complement fixation. Germinal center activation, chronic membraneous glomerulonephritis, panarteritis and simple arteriolar hyalinosis were found at sites of localization of these deposits. ImagesFig 21Fig 22Fig 23Fig 24Fig 1Fig 2Fig 3Fig 4Fig 5Fig 6Fig 25Fig 26Fig 27Fig 28Fig 29Fig 7Fig 8Fig 9Fig 10Fig 11Fig 12Fig 13Fig 14Fig 15Fig 16Fig 17Fig 18Fig 19Fig 20 PMID:4628111

Nowos?awski, Adam; Krawczy?ski, Krzysztof; Brzosko, Witold J.; Madali?ski, Kazimierz

1972-01-01

294

The Acute Effects of Alcohol on Sleep Architecture in Late Adolescence  

PubMed Central

Background Alcohol consumption is prevalent in late adolescence, however little is known about its effect on sleep in this group. In mature adults, alcohol decreases sleep onset latency (SOL) and sleep efficiency (SE) and increases wake after sleep onset (WASO). It also increases slow wave sleep (SWS) and decreases REM sleep in the first half of the night, with the inverse occurring in the second half. Alcohol’s effect on sleep during late adolescence is of interest given that this age group shows both dramatic increases in alcohol consumption, and significant developmental changes in the central nervous system. This study examined the effect of alcohol on sleep architecture in women and men aged 18–21 years and whether previously reported sleep architecture effects may have been as an artificial result of changes to sleep cycle length. Methods 24 (12 female) healthy 18–21 year old light social drinkers (19.1±1.0yrs) underwent two conditions: pre-sleep alcohol (Target BAC 0.10%) and placebo administered under controlled conditions, followed by standard polysomnography. Results In the alcohol condition, mean breath alcohol concentration (BAC) at lights out was 0.084 ±0.016%. Time in bed, total sleep time and sleep onset latency (all p>.05) did not differ between conditions. However, there was less REM (p=.011) and more stage 2 sleep (p=.035) in the alcohol condition. Further, alcohol increased SWS (p=.02) and decreased REM sleep (p<.001) in the first half of the night and disrupted sleep in the second half, with increased WASO (interaction: p=.034), and decreased SE (p=.04) and SWS (p=.01) and no REM sleep rebound in the second half of the night (p=.262). Additionally, alcohol had no effect on sleep cycle length (p=.598). Conclusions The results were broadly consistent with the adult literature with the novel extension that half night sleep architecture effects could not be attributed to changes in sleep cycle length. However, alcohol did not reduce SOL, or result in a REM rebound following reduced REM in the first half of the night. The results suggest that the effects of alcohol on sleep are modified by sleep’s prevailing developmental stage. PMID:23800287

Chan, Julia K. M.; Trinder, John; Andrewes, Holly E.; Colrain, Ian M.; Nicholas, Christian L.

2013-01-01

295

Purple sweet potato (Ipomoea batatas L.) anthocyanins: preventive effect on acute and subacute alcoholic liver damage and dealcoholic effect.  

PubMed

This study aimed to investigate the dealcoholic effect and preventive effect of anthocyanins from purple sweet potato (PSPAs) on acute and subacute alcoholic liver damage (ALD). Seven-week-old male inbred mice were grouped into five groups: control group (without PSPAs and ethanol treatments), model group (with ethanol treatment only), low-dose group (50 mg PSPAs/kg body weight), middle-dose group (125 mg PSPAs/kg body weight), and high-dose group (375 mg PSPAs/kg body weight), and the mice in all groups were administered intragastrically. Biochemical parameters of serum and liver were determined, and the histopathological changes of liver tissue were also analyzed. Results showed that all tested parameters were ameliorated after consumption of PSPAs. Therefore, PSPAs have preventive effect on acute and subacute ALD. It is suggested that PSPAs could be used as a supplementary reagent during prophylactic and curative managements of ALD. PMID:24564852

Sun, Hongnan; Mu, Taihua; Liu, Xingli; Zhang, Miao; Chen, Jingwang

2014-03-19

296

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

297

Pneumonia eosinofílica aguda num doente com infecção crónica pelo vírus da hepatite C Acute eosinophilic pneumonia in a patient with chronic hepatitis C virus infection  

Microsoft Academic Search

Acute eosinophilic pneumonia (AEP) is a cli- nical entity characterized by eosinophilic pul- monary infiltration without peripheral blood eosinophilia in most cases. We describe a case of AEP in a patient with chronic hepatitis C and review some features of the first disease.

Carmen Olabuenaga; Augusta Machado; António Oliveira e Silva; Jorge Almeida; Manuel Quintas

2003-01-01

298

Effect of allyl alcohol on hepatic transporter expression: Zonal patterns of expression and role of Kupffer cell function  

SciTech Connect

During APAP toxicity, activation of Kupffer cells is critical for protection from hepatotoxicity and up-regulation of multidrug resistance-associated protein 4 (Mrp4) in centrilobular hepatocytes. The present study was performed to determine the expression profile of uptake and efflux transporters in mouse liver following treatment with allyl alcohol (AlOH), a periportal hepatotoxicant. This study also investigated the role of Kupffer cells in AlOH hepatotoxicity, and whether changes in transport protein expression by AlOH are dependent on the presence of Kupffer cells. C57BL/6J mice received 0.1 ml clodronate liposomes to deplete Kupffer cells or empty liposomes 48 h prior to dosing with 60 mg/kg AlOH, i.p. Hepatotoxicity was assessed by plasma ALT and histopathology. Hepatic transporter mRNA and protein expression were determined by branched DNA signal amplification assay and Western blotting, respectively. Depletion of Kupffer cells by liposomal clodronate treatment resulted in heightened susceptibility to AlOH toxicity. Exposure to AlOH increased mRNA levels of several Mrp genes, while decreasing organic anion transporting polypeptides (Oatps) mRNA expression. Protein analysis mirrored many of these mRNA changes. The presence of Kupffer cells was not required for the observed changes in uptake and efflux transporters induced by AlOH. Immunofluorescent analysis revealed enhanced Mrp4 staining exclusively in centrilobular hepatocytes of AlOH treated mice. These findings demonstrate that Kupffer cells are protective from AlOH toxicity and that induction of Mrp4 occurs in liver regions away from areas of AlOH damage independent of Kupffer cell function. These results suggest that Kupffer cell mediators do not play a role in mediating centrilobular Mrp4 induction in response to periportal damage by AlOH.

Campion, Sarah N.; Tatis-Rios, Cristina [Toxicology Program, Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, 69 North Eagleville Road, Unit 3092, Storrs, CT 06269-3092 (United States); Augustine, Lisa M. [Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ (United States); Goedken, Michael J. [Department of Pathology, Schering Plough Research Institute, Lafayette, NJ (United States); Rooijen, Nico van [Department of Molecular Cell Biology, VU Medical Center, Amsterdam (Netherlands); Cherrington, Nathan J. [Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ (United States); Manautou, Jose E. [Toxicology Program, Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, 69 North Eagleville Road, Unit 3092, Storrs, CT 06269-3092 (United States)], E-mail: jose.manautou@uconn.edu

2009-04-01

299

Enhanced expression of pro-inflammatory mediators and liver X-receptor-regulated lipogenic genes in non-alcoholic fatty liver disease and hepatitis C.  

PubMed

NAFLD (non-alcoholic fatty liver disease) is one of the most frequent chronic liver diseases worldwide. The metabolic factors associated with NAFLD are also determinants of liver disease progression in chronic HCV (hepatitis C virus) infection. It has been reported that, besides inducing hepatic fatty acid biosynthesis, LXR (liver X receptor) regulates a set of inflammatory genes. We aimed to evaluate the hepatic expression of LXR? and its lipogenic and inflammatory targets in 43 patients with NAFLD, 44 with chronic HCV infection and in 22 with histologically normal liver. Real-time PCR and Western blot analysis were used to determine hepatic expression levels of LXR? and related lipogenic and inflammatory mediators in the study population. We found that the LXR? gene and its lipogenic targets PPAR-? (peroxisome-proliferator-activated receptor-?), SREBP (sterol-regulatory-element-binding protein)-1c, SREBP-2 and FAS (fatty acid synthase) were overexpressed in the liver of NAFLD and HCV patients who had steatosis. Moreover, up-regulation of inflammatory genes, such as TNF (tumour necrosis factor)-?, IL (interleukin)-6, OPN (osteopontin), iNOS (inducible NO synthase), COX (cyclo-oxygenase)-2 and SOCS (suppressors of cytokine signalling)-3, was observed in NAFLD and HCV patients. Interestingly, TNF-?, IL-6 and osteopontin gene expression was lower in patients with steatohepatitis than in those with steatosis. In conclusion, hepatic expression of LXR? and its related lipogenic and inflammatory genes is abnormally increased in NAFLD and HCV patients with steatosis, suggesting a potential role of LXR? in the pathogenesis of hepatic steatosis in these chronic liver diseases. PMID:20929443

Lima-Cabello, Elena; García-Mediavilla, María Victoria; Miquilena-Colina, María E; Vargas-Castrillón, Javier; Lozano-Rodríguez, Tamara; Fernández-Bermejo, Miguel; Olcoz, José Luis; González-Gallego, Javier; García-Monzón, Carmelo; Sánchez-Campos, Sonia

2011-03-01

300

Altered methylation and expression of ER-associated degradation factors in long-term alcohol and constitutive ER stress-induced murine hepatic tumors  

PubMed Central

Mortality from liver cancer in humans is increasingly attributable to heavy or long-term alcohol consumption. The mechanisms by which alcohol exerts its carcinogenic effect are not well understood. In this study, the role of alcohol-induced endoplasmic reticulum (ER) stress response in liver cancer development was investigated using an animal model with a liver knockout (KO) of the chaperone BiP and under constitutive hepatic ER stress. Long-term alcohol and high fat diet feeding resulted in higher levels of serum alanine aminotransferase, impaired ER stress response, and higher incidence of liver tumor in older (aged 16 months) KO females than in either middle-aged (6 months) KOs or older (aged 16 months) wild type females. In the older KO females, stronger effects of the alcohol on methylation of CpG islands at promoter regions of genes involved in the ER-associated degradation (ERAD) were also detected. Altered expression of ERAD factors including derlin 3, Creld2 (cysteine-rich with epidermal growth factor-like domains 2), Herpud1 (homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member), Wfs1 (Wolfram syndrome gene), and Yod1 (deubiquitinating enzyme 1) was co-present with decreased proteasome activities, increased estrogen receptor ? variant (ER?36), and enhanced phosphorylations of ERK1/2 (extracellular signal-regulated protein kinases 1 and 2) and STAT3 (the signal transducers and activators of transcription) in the older KO female fed alcohol. Our results suggest that long-term alcohol consumption and aging may promote liver tumorigenesis in females through interfering with DNA methylation and expression of genes involved in the ERAD. PMID:24198826

Han, Hui; Hu, Jay; Lau, Mo Y.; Feng, Min; Petrovic, Lydia M.; Ji, Cheng

2013-01-01

301

Acute Stress and Event-Related Potential Correlates of Attention to Alcohol Images in Social Drinkers  

PubMed Central

Objective: The use of alcohol to cope with stress is a major health concern, yet the neurophysiological mechanisms underlying the effects of stress on alcohol-related cognition are not well understood. This study examined changes in event-related potentials (ERPs) elicited by alcohol-related images before and after a stressor compared with a control condition. Method: Social drinkers (N = 75; 38 male) were assigned to one of two target subgroups for completion of an oddball task: (a) to detect alcohol targets while ignoring household object distracters and frequently presented nonsense shapes or (b) to detect object targets while ignoring alcohol distracters and nonsense shapes. ERPs were recorded before and after one of two conditions: a stressor or a nonstressful control task. Results: N200 latency and amplitude changes were modulated by stress. Similarly, stress reduced P300 latencies beyond practice effects. For P300 amplitude, the target subgroup interacted with the condition such that the standard “oddball” effect was observed in the control condition but was absent in the stress condition, suggesting that stress may have interfered with the participants’ cognitive efficiency, or the ability to ignore task-irrelevant stimuli. Conclusions: These findings suggest that stress influences the early stages of alcohol-related processing, an effect that may be particularly apparent in ERP latencies. These findings have implications for understanding the neural mechanisms involved with stress and alcohol cue reactivity. PMID:22846240

Ceballos, Natalie A.; Giuliano, Ryan J.; Wicha, Nicole Y.Y.; Graham, Reiko

2012-01-01

302

Event-level associations between affect, alcohol intoxication, and acute dependence symptoms: Effects of urgency, self-control, and drinking experience  

PubMed Central

This study used experience sampling to examine within-person associations between positive affect, anxiety, sadness, and hostility and two outcomes: alcohol intoxication and acute dependence symptoms. We examined the role of urgency, premeditation, and perseverance in predicting the alcohol outcomes and tested whether the affective associations varied as a function of urgency. Participants completed baseline assessments and 21 days of experience sampling on PDAs. Hypotheses were partially confirmed. Positive affect was positively, and sadness inversely, associated with intoxication. Hostility was associated with intoxication for men but not women. Negative urgency moderated the association between anxiety and intoxication, making it stronger. However, positive urgency did not moderate the effect of positive affect. Heavier drinkers exhibited the greatest number of symptoms, yet the association between intoxication and acute signs of alcohol disorder were attenuated among these individuals. Results support the use of experience sampling to study acute signs and symptoms of high risk drinking and dependence. PMID:20685044

Simons, Jeffrey S.; Dvorak, Robert D.; Batien, Bryan D.; Wray, Tyler B.

2012-01-01

303

Acute illness-induced behavioral alterations are similar to those observed during withdrawal from acute alcohol exposure  

PubMed Central

Exposure to an immunogen results in a constellation of behavioral changes collectively referred to as “sickness behaviors,” with alterations in cytokine expression previously shown to contribute to this sickness response. Since behaviors observed during ethanol withdrawal are strikingly similar to sickness behaviors, we hypothesized that behavioral manifestations of ethanol withdrawal might be an expression of sickness behaviors induced by ethanol-related changes in peripheral and/or central cytokine expression. Accordingly, behaviors exhibited during a modified social investigation test were first characterized in male rats following an acute injection of lipopolysaccharide (LPS; 100 ?g/kg). Subsequently, behavioral changes after either a high (4-g/kg; Experiment 2) or low dose (0.5 g/kg; Experiment 3) of ethanol were also examined in the same social investigation test, as well as in the forced-swim test (FST; Experiment 4). Results from these experiments demonstrated similar reductions in both exploration and social investigatory behavior during acute illness and ethanol withdrawal, while a seemingly paradoxical decrease in immobility was observed in the FST during acute ethanol withdrawal. In follow-up studies, neither indomethacin (Experiment 5) nor interleukin-1 receptor antagonist (Experiment 6) pre-exposure reversed the ethanol withdrawal-induced behavioral changes observed in this social investigation test. Taken together, these studies demonstrate that the behavioral sequelae of acute illness and ethanol withdrawal are similar in nature, while antagonist studies suggest that these behavioral alterations are not reversed by blockade of IL-1 receptors or inhibition of prostaglandin synthesis. Though a direct mechanistic link between cytokines and the expression of acute ethanol withdrawal-related behaviors has yet to be found, future studies examining the involvement of brain cytokines as potential mediators of ethanol effects are greatly needed. PMID:22921768

Richey, Laura; Doremus-Fitzwater, Tamara L.; Buck, Hollin M.; Deak, Terrence

2012-01-01

304

Lack of variant specific CD8+ T-cell response against mutant and pre-existing variants leads to outgrowth of particular clones in acute hepatitis C  

PubMed Central

Background CTL escape mutations have been described during acute hepatitis C in patients who developed chronic disease later on. Our aim was to investigate the mutual relationship between HCV specific CD8+ T cells and evolution of the viral sequence during early acute HCV infection. Results We sequenced multiple clones of NS3 1406 epitope in 4 HLA-A*02 patients with acute hepatitis C genotype 1b infection. Pentamers specific for the variants were used to monitor the corresponding CD8+ T cell response. We observed outgrowth of mutations, which induced only a weak and thus potentially insufficient CD8+ T cell response. In one patient we observed outgrowth of variant epitopes with similarities to a different genotype rather than de novo mutations most probably due to a lack of responsiveness to these likely pre-existing variants. We could show that in acute hepatitis C CTL escape mutations occur much earlier than demonstrated in previous studies. Conclusions The adaption of the virus to a new host is characterized by a high and rapid variability in epitopes under CD8+ T cell immune pressure. This adaption takes place during the very early phase of acute infection and strikingly some sequences were reduced below the limit of detection at some time points but were detected at high frequency again at later time points. Independent of the observed variability, HCV-specific CD8+ T cell responses decline and no adaption to different or new antigens during the course of infection could be detected. PMID:24073713

2013-01-01

305

Lymphocyte proliferation to Phytohemagglutinin (PHA) in hepatitis B antigen-positive and -negative hepatitis  

Microsoft Academic Search

Summary Lymphocytes from patients with HBs-Ag-positive and -negative acute, chronic-persistent, and chronic-active hepatitis, from healthy controls and from patients with alcoholic liver cirrhosis were tested under standardized conditions. These included use of a single charge of Phytohemagglutinin (PHA-P) dissolved and diluted in one operation, of a single pool of homologous serum of the major blood group AB found free of

C.-P. Sodomann; M. Rother; K. Havemann; G. A. Martini

1979-01-01

306

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

Microsoft Academic Search

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

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

2001-01-01

307

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

Microsoft Academic Search

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

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

2009-01-01

308

Long-Term Outcome of Liver Resection for Hepatocellular Carcinoma in Noncirrhotic Nonfibrotic Liver with No Viral Hepatitis or Alcohol Abuse  

Microsoft Academic Search

Background  Hepatocellular carcinoma (HCC) occurs primarily in cirrhotic liver, with less than 10% occurring in normal liver parenchyma.\\u000a Limited studies have described the outcome of liver resection in strictly normal liver parenchyma with no cirrhosis, fibrosis,\\u000a underlying viral hepatitis, alcohol abuse, or dysmetabolic syndrome.\\u000a \\u000a \\u000a \\u000a Materials and methods  Between January 1986 and 2005, a total of 321 patients were referred to our institution

Jean Lubrano; Emmanuel Huet; Basile Tsilividis; Arnaud François; Odile Goria; Ghassan Riachi; Michel Scotté

2008-01-01

309

Acute effects of alcohol on brain perfusion monitored with arterial spin labeling magnetic resonance imaging in young adults.  

PubMed

While a number of studies have established that moderate doses of alcohol increase brain perfusion, the time course of such an increase as a function of breath alcohol concentration (BrAC) has not yet been investigated, and studies differ about regional effects. Using arterial spin labeling (ASL) magnetic resonance imaging, we investigated (1) the time course of the perfusion increase during a 15-minute linear increase of BrAC up to 0.6?g/kg followed by a steady exposure of 100?minutes, (2) the regional distribution, (3) a potential gender effect, and (4) the temporal stability of perfusion effects. In 48 young adults who participated in the Dresden longitudinal study on alcohol effects in young adults, we observed (1) a 7% increase of global perfusion as compared with placebo and that perfusion and BrAC are tightly coupled in time, (2) that the increase reaches significance in most regions of the brain, (3) that the effect is stronger in women than in men, and (4) that an acute tolerance effect is not observable on the time scale of 2?hours. Larger studies are needed to investigate the origin and the consequences of the effect, as well as the correlates of inter-subject variations. PMID:24398943

Marxen, Michael; Gan, Gabriela; Schwarz, Daniel; Mennigen, Eva; Pilhatsch, Maximilian; Zimmermann, Ulrich S; Guenther, Matthias; Smolka, Michael N

2014-03-01

310

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

311

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

312

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

313

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

PubMed

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

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

2014-12-15

314

Therapy with Interleukin-22 Alleviates Hepatic Injury and Hemostasis Dysregulation in Rat Model of Acute Liver Failure  

PubMed Central

The therapeutic efficacy of interleukin-22 (IL-22) on liver injury and hematological disturbances was studied in rat model of acute liver failure (ALF) induced by D-galactosamine/lipopolysaccharide (D-GalN/LPS). The following parameters were investigated: (1) survival rate, (2) serum levels of liver function enzymes (aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP)), total bilirubin (TBILI), and total albumen (ALB), (3) blood clotting tests (prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen level (FIB)) and white blood cells (WBCs), red blood cells (RBCs), and platelet counts, (4) hepatic levels of tumor necrosis factor-? (TNF-?) and cyclooxygenase-2 (COX-2), and (5) liver histopathology. After 48 hours of D-GalN/LPS, the rats exhibited 20% mortality, significant increases in AST, ALT, ALP, TBILI, PT, and aPTT, TNF-?, and COX-2 and significant decreases in FIB, WBCs, and RBCs. By contrast, therapy with IL-22 prevented the lethal effect of D-GalN/LPS by 100% and efficiently alleviated all the biochemical and hematological abnormalities that were observed in ALF untreated group. Furthermore, IL-22 treatment decreased the hepatic contents of TNF-? and COX-2. The histopathological findings also supported the hepatoprotective effect of IL-22. Taken together, therapy with IL-22 can represent a promising therapeutic tool against liver injury and its associated hemostasis disturbances. PMID:24799907

Ashour, Tariq Helal

2014-01-01

315

Linking GABA(A) receptor subunits to alcohol-induced conditioned taste aversion and recovery from acute alcohol intoxication.  

PubMed

GABA type A receptors (GABA(A)-R) are important for ethanol actions and it is of interest to link individual subunits with specific ethanol behaviors. We studied null mutant mice for six different GABA(A)-R subunits (?1, ?2, ?3, ?4, ?5 and ?). Only mice lacking the ?2 subunit showed reduction of conditioned taste aversion (CTA) to ethanol. These results are in agreement with data from knock-in mice with mutation of the ethanol-sensitive site in the ?2-subunit (Blednov et al., 2011). All together, they indicate that aversive property of ethanol is dependent on ethanol action on ?2-containing GABA(A)-R. Deletion of the ?2-subunit led to faster recovery whereas absence of the ?3-subunit slowed recovery from ethanol-induced incoordination (rotarod). Deletion of the other four subunits did not affect this behavior. Similar changes in this behavior for the ?2 and ?3 null mutants were found for flurazepam motor incoordination. However, no differences in recovery were found in motor-incoordinating effects of an ?1-selective modulator (zolpidem) or an ?4-selective agonist (gaboxadol). Therefore, recovery of rotarod incoordination is under control of two GABA(A)-R subunits: ?2 and ?3. For motor activity, ?3 null mice demonstrated higher activation by ethanol (1 g/kg) whereas both ?2 (-/-) and ?3 (-/Y) knockout mice were less sensitive to ethanol-induced reduction of motor activity (1.5 g/kg). These studies demonstrate that the effects of ethanol at GABAergic synapses containing ?2 subunit are important for specific behavioral effects of ethanol which may be relevant to the genetic linkage of the ?2 subunit with human alcoholism. PMID:23147414

Blednov, Y A; Benavidez, J M; Black, M; Chandra, D; Homanics, G E; Rudolph, U; Harris, R A

2013-04-01

316

5 Natural history of hepatitis C  

Microsoft Academic Search

SUMMARY Hepatitis B virus (HBV) infection can cause acute, fulminant or chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). Perinatally or childhood acquired HBV infection usually causes subclinical or anicteric acute hepatitis and is associated with a high risk of chronicity (30 to 90% of cases), whereas adult acquired infection may cause acute symptomatic hepatitis (approximately 30% of patients) and

Leonard B. Seeff

2000-01-01

317

Deficit in brain reward function and acute and protracted anxiety-like behavior after discontinuation of a chronic alcohol liquid diet in rats  

Microsoft Academic Search

Rationale  Discontinuation of chronic and excessive alcohol consumption leads to a dysphoric state in humans. It is not known if there\\u000a are changes in brain reward function after the discontinuation of an alcohol liquid in rats.\\u000a \\u000a \\u000a \\u000a Objectives  The aim of these studies was to investigate the effect of withdrawal from an alcohol liquid diet on brain reward function\\u000a and acute and protracted

Daria Rylkova; Hina P. Shah; Elysia Small; Adrie W. Bruijnzeel

2009-01-01

318

Mechanisms of the Hepatic Acute-Phase Response during Bacterial Pneumonia  

Microsoft Academic Search

The acute-phase response is characterized by increased circulating levels of acute-phase proteins (APPs) generated by the liver. During bacterial pneumonia, APPs correlate with the severity of disease, serve as biomarkers, and are functionally significant. The kinetics and regulatory mechanisms of APP induction in the liver during lung infection have yet to be defined. Here we show that APP mRNA transcription

Lee J. Quinton; Matthew R. Jones; Bryanne E. Robson; Joseph P. Mizgerd

2009-01-01

319

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

320

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

321

[Acute and chronic alcohol abuse--effect on inpatient treatment of trauma surgery patients].  

PubMed

The effect of alcoholism on the length of stay and costs of hospital treatment is not well documented. The posttraumatic course of treatment of 75 alcohol intoxicated patients was prospectively followed. A shortened MAST-test served to identify chronic alcoholised patients. The obtained data were compared with a control group according to the matched-pair method. The course of treatment of 44 drunken patients without signs of chronic alcoholism was not different from the control group. However 31 chronic alcohol intoxicated patients showed a clearly different course from the control group. The hospital stay was nearly doubled (13.5 days) compared to the control group (7.5 days). There were explicitly more consultations of specialists (26 vs. 9) necessary and the complication rate (9 vs. 1) during the hospital stay was significantly increased. Chronic alcoholism of traumatised patients yields to a cost increase of the hospital treatment. The high complication rate forces an intensive supervision of the affected patients. These results have to be taken into account by calculations of reimbursement rates for the field of trauma surgery. PMID:7975941

Ring, T; Sattler, R W

1994-01-01

322

Acute hepatitis after starting pinaverium bromide in a patient taking mirtazapine.  

PubMed

A 56-year-old man presented with chronic abdominal pain. He had been evaluated extensively in the recent past undergoing upper gastrointestinal endoscopy, colonoscopy and CT scan of the abdomen with normal results. The provisional diagnosis of irritable bowel syndrome was performed and pinaverium bromide was started. The patient had pre-existing hypertension, a major depressive disorder and gastro-oesophageal reflux disease. He had been taking nebivolol and pantoprazole for several years and mirtazapine for the last 1 year. The patient developed nausea, vomiting and anorexia after 5 days of starting pinaverium bromide. Investigations revealed marked elevation of liver enzymes and bilirubin. He was negative for HIV, HBSAg, anti-hepatitis C virus, IgM for hepatitis A virus, hepatitis E virus, antinuclear antibody and antimitochondrial antibody. An ultrasound showed mild hepatomegaly with hypoechoic echo texture; the rest of scan was normal. Pinaverium and mirtazapine were stopped immediately. The patient was treated symptomatically and his liver profile returned to normal after 4 weeks. PMID:25015163

Tak, Sandeep; Tak, Shubhanjali

2014-01-01

323

Acute hepatitis C virus infection in young adult injection drug users: a prospective study of incident infection, resolution and reinfection  

PubMed Central

Background Hepatitis C virus (HCV) infection, clearance and reinfection are best studied in injection drug users (IDU) who have the highest incidence and are representative of most infections. Methods A prospective cohort of HCV negative young IDU was followed from 2000 to 2007, to identify acute and incident HCV and prospectively study infection outcomes. Results Among 1,191 young IDU screened, 731 (61.4%) were HCV negative, and 520 (71.1%) were enrolled into follow-up. Cumulative HCV incidence was 26.7 per 100 person years of observation (PYO) (95% CI, 21.5, 31.6). 95 (70.4%) of 135 acute/incident HCV infections were followed; 21% cleared HCV. Women had a significantly higher incidence of viral clearance compared to men (age-adjusted relative hazard 2.91, 95% CI, 1.68, 5.03) and also showed a significantly faster rate of early HCV viremia decline. Estimated reinfection rate was 24.6 per 100 PYO (95% CI, 11.7, 51.6). Among seven individuals, multiple episodes of HCV reinfection and re-clearance were observed. Conclusions In this large sample of young IDU, females show demonstrative differences in their rates of viral clearance and kinetics of early viral decline. Recurring reinfection and re-clearance suggest possible protection against persistent infection. These results should inform HCV clinical care and vaccine development. PMID:19764883

Page, Kimberly; Hahn, Judith A.; Evans, Jennifer; Shiboski, Stephen; Lum, Paula; Delwart, Eric; Tobler, Leslie; Andrews, William; Avanesyan, Lia; Cooper, Stewart; Busch, Michael P.

2010-01-01

324

Upregulation of heat shock protein 32 with hemin alleviates acute heat-induced hepatic injury in mice.  

PubMed

Heat shock protein 32 (HSP32) is a stress response protein that can be induced by heat stress in the liver, and its induction can act as an important cellular defence mechanism against heat-induced liver injury. To investigate the functional role of HSP32 in protecting liver tissue against heat stress in mice and the mechanism by which it achieves this protective effect, HSP32 expression and carbon monoxide (CO) contents in a model of mice subjected to acute, transient heat exposure were examined. Furthermore, functional and histological parameters of liver damage and the possible involvement of oxidative stress to induce oxidative deterioration of liver functions and caspase-3 expression were also investigated in this study. We found that heat treatment of mice produced severe hepatic injury, whereas upregulation of HSP32 with hemin pretreatment prevented mice from liver damage. In contrast, addition of Sn-protoporphyrin (SnPP) to inhibit HSP32 expression completely reversed its hepatoprotective effect. It is concluded that upregulation of HSP32 by hemin could alleviate acute heat-induced hepatocellular damage in mice, and its by-product CO seems to play a more important role in hepatoprotective mechanism. PMID:24473736

Li, Cheng-Min; Li, Lian; Wu, Jie; Bai, Jing-Yan; Sun, Yu; Huang, Shuai; Wang, Gen-Lin

2014-09-01

325

Novel protocol including liver biopsy to identify and treat CD8+ T-cell predominant acute hepatitis and liver failure.  

PubMed

In the majority of children with ALF, the etiology is unknown and liver transplantation is often needed for survival. A patient case prompted us to consider that immune dysregulation may be the cause of indeterminate acute hepatitis and liver failure in children. Our study includes nine pediatric patients treated under a multidisciplinary clinical protocol to identify and treat immune-mediated acute liver injury. Patients with evidence of inflammation and no active infection on biopsy received treatment with intravenous immune globulin and methylprednisolone. Seven patients had at least one positive immune marker before or after treatment. All patients had a CD8+ T-cell predominant liver injury that completely or partially responded to immune therapy. Five of the nine patients recovered liver function and did not require liver transplantation. Three of these patients subsequently developed bone marrow failure and were treated with either immunosuppression or stem cell transplant. This series highlights the importance of this tissue-based approach to diagnosis and treatment that may improve transplant-free survival. Further research is necessary to better characterize the immune injury and to predict the subset of patients at risk for bone marrow failure who may benefit from earlier and stronger immunosuppressive therapy. PMID:24930635

McKenzie, Rebecca B; Berquist, William E; Nadeau, Kari C; Louie, Christine Y; Chen, Sharon F; Sibley, Richard K; Glader, Bertil E; Wong, Wendy B; Hofmann, Lawrence V; Esquivel, Carlos O; Cox, Kenneth L

2014-08-01

326

Plasma interferon-gamma-inducible protein-10 (IP-10) levels during acute hepatitis C virus infection  

PubMed Central

Systemic levels of interferon-gamma-inducible protein-10 (IP-10) are predictive of treatment-induced clearance in chronic HCV. In the present study, factors associated with plasma IP-10 levels at the time of acute HCV detection and the association between IP-10 levels and spontaneous clearance were assessed in three cohorts of acute HCV infection. Among 300 individuals, 245 (181 male, 47 HIV+) were HCV RNA+ at acute HCV detection. In adjusted analysis, factors independently associated with IP-10 levels ?150 pg/mL (median level) included HCV RNA levels >6 log IU/mL, HIV co-infection and non-Aboriginal ethnicity. Among 245 HCV RNA+ at acute HCV detection, 214 were untreated (n=137) or had persistent infection (infection duration ?26 weeks) at treatment initiation (n=77). Spontaneous clearance occurred in 14% (29 of 214). Individuals without spontaneous clearance had significantly higher mean plasma IP-10 levels at the time of acute HCV detection than those with clearance (248±32 vs. 142±22 pg/mL, P=0.008). The proportion of individuals with spontaneous clearance was 0% (0 of 22, P=0.048) and 16% (27 of 165) and in those in those with and without plasma IP-10 levels ?380 pg/mL. In adjusted analyses, favourable IL28B genotype was associated with spontaneous clearance, while higher HCV RNA level was independently associated with lower odds of spontaneous clearance. Conclusion High IP-10 levels at acute HCV detection were associated with failure to spontaneously clear HCV. Patients with acute HCV and high baseline IP-10 levels, particularly >380 pg/mL, should be considered for early therapeutic intervention, and those with low levels should defer therapy for potential spontaneous clearance. PMID:23325615

Grebely, Jason; Feld, Jordan J.; Applegate, Tanya; Matthews, Gail V.; Hellard, Margaret; Sherker, Alana; Petoumenos, Kathy; Zang, Geng; Shaw, Ineke; Yeung, Barbara; George, Jacob; Teutsch, Suzy; Kaldor, John M.; Cherepanov, Vera; Bruneau, Julie; Shoukry, Naglaa H.; Lloyd, Andrew R.; Dore, Gregory J.

2013-01-01

327

Circulating microRNAs: promising candidates serving as novel biomarkers of acute hepatitis  

PubMed Central

Acute liver failure as life threatening condition comprises a difficult diagnostic situation to evaluate potential outcomes and therapeutic options. Thus, prognostic indicators are urgently needed for evaluation of progression of liver injury, clinical outcome, prognosis, and for therapeutic response. Recently, circulating microRNA, in particular miR-122, was described as a potential biomarker of acute liver injury after intoxication of mice. Circulating microRNA (miRNA) molecules are very stable and RNase-resistant due to protein aggregation and vesicle enclosure. Since miRNA species are known to be associated with chronic liver damage or with liver cancer, circulating miRNA patterns are suggested to serve also as reporters for progression of acute liver failure. miRNA profiling analyses using PCR arrays or next generation sequencing, may achieve identification of miRNA species that are linked to the rapid progression of acute liver injury, to the outcome of liver failure, or to the therapeutic response. Therefore, circulating miRNAs are promising, non-invasive biomarkers of future diagnostic approaches. However, normalisation of circulating miRNA levels is essential and further standardisation of miRNA quantification assays is needed. PMID:23267332

Elfimova, Natalia; Schlattjan, Martin; Sowa, Jan-Peter; Dienes, Hans Peter; Canbay, Ali; Odenthal, Margarete

2012-01-01

328

Acute Alcohol Intake Induces SOCS1 and SOCS3 and Inhibits Cytokine-Induced STAT1 and STAT3 Signaling in Human Monocytes  

PubMed Central

Background Acute alcohol consumption is associated with induction of immuno-inhibitory cytokines and down-regulation of pro-inflammatory responses to various pathogens. We previously reported that alcohol activates janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling leading to IL-10 induction. The JAK-STAT pathway also activates its own negative regulators, suppressors of cytokine signaling (SOCS) 1 and SOCS3. SOCS proteins are inducible inhibitors that negatively regulate STAT3/STAT1 signaling pathways induced by cytokines, IL-6 or IFNs. Here we aimed to explore the effect of acute alcohol on induction of SOCS1/SOCS3 and regulation of STAT3/STAT1 pathways induced by IL-6 or IFNs in human monocytes. Methods Blood samples from normal volunteers were collected before and 24 hours after consumption of 2 ml vodka/kg body weight. For in vitro experiments human monocytes were pretreated with ethanol (EtOH) followed by stimulation with cytokines; proteins were analyzed by Western blot, nuclear protein binding to DNA by EMSA, and RNA by real time PCR. Results: Acute in vivo or in vitro alcohol treatment increased both SOCS1 and SOCS3 RNA expression in monocytes. Alcohol treatment resulted in increased STAT3 and STAT1 DNA binding capacity. Activation of both STAT1 and STAT3 has been shown to induce SOCS1/3. We hypothesized that induction of SOCS proteins by alcohol in turn may lead to modulation of cytokine signaling through STAT1 and STAT3. Indeed, we observed significant down-regulation of IL-6-, IFN?- and IFN?-induced STAT1 DNA binding as well as inhibition of IL-6- and IFN?-induced STAT3 when alcohol was added to monocytes 3 hours prior to the cytokine stimulation. Consistent with inhibition of IL-6-induced STAT3 DNA binding in alcohol-pretreated cells, the levels of IL-6-dependent genes, MCP-1 and ICAM-1, was reduced after IL-6 stimulation. Similar to EtOH alone, combined EtOH+IL-6 simulation resulted in increased expression of both SOCS3 and SOCS1 genes. Conclusion While acute alcohol treatment alone activates STAT1/3 signaling pathways and induces SOCS3 and SOCS1 levels in monocytes, alcohol also leads to down-regulation of IL-6-, IFN?-, and IFN?-induced signaling via STAT1/STAT3 pathways, likely through excessive SOCS activation. PMID:18616672

Norkina, Oxana; Dolganiuc, Angela; Catalano, Donna; Kodys, Karen; Mandrekar, Pranoti; Syed, Amber; Efros, Marian; Szabo, Gyongyi

2014-01-01

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

Endovascular Treatment of Pseudoaneurysm of the Common Hepatic Artery with Intra-aneurysmal Glue (N-Butyl 2-Cyanoacrylate) Embolization  

SciTech Connect

A 40-year-old man, a chronic alcoholic, presented with acute epigastric pain. Selective celiac arteriography showed a pseudoaneurysm arising from the common hepatic artery. We hereby describe a technical innovation where complete pseudoaneurysm exclusion was seen after intra-aneurysmal N-butyl 2-cyanoacrylate (glue) injection with preservation of antegrade hepatic arterial flow and conclude that intra-aneurysmal liquid injection may have potential as a therapeutic option to reconstruct a defective vessel wall and thereby maintain the antegrade flow.

Garg, Ashwin, E-mail: ashwin_garg@yahoo.co.in; Banait, Swati; Babhad, Sudeep; Kanchankar, Niraj; Nimade, Pradeep; Panchal, Chintan [Lokmanya Tilak Medical College and Municipal General Hospital, Department of Radiology (India)

2007-09-15

331

Hepatic sulfotransferase as a nephropreventing target by suppression of the uremic toxin indoxyl sulfate accumulation in ischemic acute kidney injury.  

PubMed

Ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) is evoked by diverse pathophysiological conditions and/or surgical procedures. Here, we evaluated the nephropreventive effect of sulfotransferase (SULT) inhibitors, quercetin, and resveratrol, which hamper hepatic indoxyl sulfate (IS) production. I/R of the kidney caused severe renal injury with marked accumulation of serum and renal IS and urinary excretion of kidney injury molecule-1. Oral administration of AST-120 resulted in a significant restoration of kidney injury, suggesting that uremic toxins, which can be suppressed or adsorbed by AST-120 in the intestine, contribute to the progression or development of I/R-induced AKI. Oral administration of resveratrol or quercetin, SULT inhibitors, suppressed IS accumulation, accompanied by significant amelioration of renal dysfunction. The expression of nuclear factor E2-related factor 2 (Nrf2) in the renal nuclear fractions was markedly elevated by renal I/R, but suppressed by treatment with SULT inhibitors. IS is primarily taken up by HK-2 cells derived from human proximal tubular cells via organic anion transporters, which then evokes activation of Nrf2, most likely due to intracellular oxidative stress. Renal basolateral organic anion transporters OAT1 and OAT3, which mediate renal tubular uptake of IS in basolateral membrane, were markedly downregulated by renal I/R, but restored by SULT inhibitors. Our results suggest that renal accumulation of IS in ischemic AKI induces oxidative stress and downregulation of organic anion transporters resulting in kidney damage, which could be restored to some extent by inhibiting hepatic SULT activity as a nephropreventive target. PMID:24958931

Saito, Hideyuki; Yoshimura, Misato; Saigo, Chika; Komori, Megumi; Nomura, Yui; Yamamoto, Yuko; Sagata, Masataka; Wakida, Ayaka; Chuman, Erina; Nishi, Kazuhiko; Jono, Hirofumi

2014-09-01

332

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

333

Acute ethanol poisoning in a 6-year-old girl following ingestion of alcohol-based hand sanitizer at school  

PubMed Central

BACKGROUND: Alcohol-based hand sanitizers (ABHSs) have been widely used in homes, workplaces and schools to prevent the spread of infectious diseases. We report a young child unintentionally ingested ABHS at a school, resulting in intoxication. METHODS: The child was a 6-year-old girl who had been brought to the emergency department (ED) for hypothermia, altered mental status (AMS), periods of hypoventilation, hypothermia and vomiting. Computed tomography of her head revealed nothing abnormal in intracranial pathology. Urine drug screening was negative. Alcohol level was 205 mg/dL on admission. Other abnormal values included potassium of 2.8 mEq/L, osmolality of 340 mOsm/kg and no hypoglycemia. Further investigation revealed that the patient had gone frequently to the class restroom for ingestion of unknown quantities of ABHSs during the day. The patient was admitted for one day for intravenous fluid hydration and close observation of her mental status. RESULTS: The patient was discharged from the hospital the next day without any complications. CONCLUSION: Despite the large safety margin of ABHSs, emergency physicians need to be aware of the potential risk of ingestion of a large amount of such products in children and consider it in the assessment and management of school-age children with acute AMS.

Joseph, Madeline Matar; Zeretzke, Cristina; Reader, Sara; Sollee, Dawn R.

2011-01-01

334

An insight into the possible protective effect of pyrrolidine dithiocarbamate against lipopolysaccharide-induced oxidative stress and acute hepatic injury in rats  

PubMed Central

Lipopolysaccharide (LPS) is a major cell wall molecule of Gram-negative bacteria known to stimulate the synthesis and secretion of several toxic metabolites, such as reactive oxygen species. In this study, the effect of pyrrolidine dithiocarbamate (PDTC), an antioxidant with nuclear factor-?B inhibitor activity, was evaluated in LPS-induced oxidative stress and acute hepatic injury in rats. Animals were pretreated for 3 consecutive days with PDTC (200 mg/kg/day, i.p.) or saline and animals were then challenged with LPS (6 mg/kg, i.p.) or saline. Six hours after LPS injection, animals were decapitated and blood and liver samples were collected to assess the chosen biochemical parameters. Saline-pretreated animals challenged with LPS revealed extensive liver damage, as evidenced by increases in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transferase (?-GT). Also, LPS treatment resulted in significant increases in serum lactate dehydrogenase (LDH), tumor necrosis factor-alpha (TNF-?) and nitrite levels. Furthermore, LPS challenge caused oxidative stress as indicated by an increase in hepatic lipid peroxidation measured as thiobarbituric acid reactive substances (TBARS) and a decrease in hepatic reduced glutathione concentration (GSH) as well as decreased activities of superoxide dismutase (SOD) and catalase in hepatic tissues. The administration of PDTC prior to LPS challenge resulted in improved liver functions as evidenced by the decline in serum AST, ALT, ?-GT levels and reduction in serum LDH, TNF-? and nitrite levels. Moreover, PDTC reduced the chosen lipid peroxidation marker, TBARS and increased GSH concentration, and SOD and catalase activities in hepatic tissues. These results indicate that PDTC may be a useful pharmacological agent in alleviating LPS-induced oxidative stress and acute hepatic injury. PMID:23960709

Hagar, Hanan H.

2009-01-01

335

An insight into the possible protective effect of pyrrolidine dithiocarbamate against lipopolysaccharide-induced oxidative stress and acute hepatic injury in rats.  

PubMed

Lipopolysaccharide (LPS) is a major cell wall molecule of Gram-negative bacteria known to stimulate the synthesis and secretion of several toxic metabolites, such as reactive oxygen species. In this study, the effect of pyrrolidine dithiocarbamate (PDTC), an antioxidant with nuclear factor-?B inhibitor activity, was evaluated in LPS-induced oxidative stress and acute hepatic injury in rats. Animals were pretreated for 3 consecutive days with PDTC (200 mg/kg/day, i.p.) or saline and animals were then challenged with LPS (6 mg/kg, i.p.) or saline. Six hours after LPS injection, animals were decapitated and blood and liver samples were collected to assess the chosen biochemical parameters. Saline-pretreated animals challenged with LPS revealed extensive liver damage, as evidenced by increases in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transferase (?-GT). Also, LPS treatment resulted in significant increases in serum lactate dehydrogenase (LDH), tumor necrosis factor-alpha (TNF-?) and nitrite levels. Furthermore, LPS challenge caused oxidative stress as indicated by an increase in hepatic lipid peroxidation measured as thiobarbituric acid reactive substances (TBARS) and a decrease in hepatic reduced glutathione concentration (GSH) as well as decreased activities of superoxide dismutase (SOD) and catalase in hepatic tissues. The administration of PDTC prior to LPS challenge resulted in improved liver functions as evidenced by the decline in serum AST, ALT, ?-GT levels and reduction in serum LDH, TNF-? and nitrite levels. Moreover, PDTC reduced the chosen lipid peroxidation marker, TBARS and increased GSH concentration, and SOD and catalase activities in hepatic tissues. These results indicate that PDTC may be a useful pharmacological agent in alleviating LPS-induced oxidative stress and acute hepatic injury. PMID:23960709

Hagar, Hanan H

2009-10-01

336

Putative cis-Acting Stem-Loops in the 5' Untranslated Region of the Severe Acute Respiratory Syndrome Coronavirus Can Substitute for Their Mouse Hepatitis Virus Counterparts  

Microsoft Academic Search

Consensus covariation-based secondary structural models for the 5! 140 nucleotides of the 5! untranslated regions (5! UTRs) from mouse hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus (SCoV) were developed and predicted three major helical stem-loop structures, designated stem-loop 1 (SL1), SL2, and SL4. The SCoV 5! UTR was predicted to contain a fourth stem-loop, named SL3, in which

Hyojeung Kang; Min Feng; Megan E. Schroeder; David P. Giedroc; Julian L. Leibowitz

2006-01-01

337

Antibodies against human liver-specific protein (LSP) in acute and chronic viral hepatitis types A, B and non-A, non-B.  

PubMed Central

Sera from 42 patients with acute viral hepatitis (AVH), 97 patients with chronic active liver disease (CALD) and 89 controls were tested by radioimmunoprecipitation for the presence of antibodies against human liver-specific protein (LSP). Anti-LSP were found in all but one patient with AVH type A (93%) and in a smaller percentage of AVH type B (55%). In non-A, non-B cases, anti-LSP were found in low percentages: 27% in acute cases, 10% in chronic cases. Furthermore, in CALD, a significant difference was found between HBsAg-positive CAH and 'autoimmune' CAH, a significant difference was found between HBsAg-positive CAH and 'autoimmune' CAH, both in anti-LSP prevalence (21%, 67%; P less than 0.005) and in anti-LSP titre (1:154 +/- 170, 1:316 +/- 186; P less than 0.005). In HBsAg-negative/anti-HBc-positive CAH, three of 15 patients were anti-LSP positive. Anti-LSP were found only in three of 57 patients with various non-hepatic diseases with autoimmune features. None of the 12 healthy HBsAg carriers was positive. Hence there is evidence for a considerable heterogeneity in anti-LSP response in acute and in chronic inflammatory HBsAg-negative liver diseases. These data suggest that anti-LSP antibodies do not play a prominent role in the process of transition to chronicity of acute viral hepatitis particularly in non-A, non-B cases, whereas these antibodies may be important in the mechanism of ongoing liver cell injury in patients with 'autoimmune' CAH, and can represent a useful diagnostic marker of this type of hepatitis. PMID:6802539

Meliconi, R; Baraldini, M; Stefanini, G F; Facchini, A; Miglio, F; Bortolotti, F; Alberti, A; Realdi, G; Amoroso, P

1981-01-01

338

Predictive value of intrahepatic hepatitis B virus covalently closed circular DNA and total DNA in patients with acute hepatitis B and patients with chronic hepatitis B receiving anti?viral treatment.  

PubMed

This study aimed to investigate the persistence and predictive values of intrahepatic (IH) hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and total DNA (tDNA) in patients with acute hepatitis B (AHB) and patients with chronic hepatitis B (CHB) receiving anti?viral treatment. The levels of IH cccDNA and tDNA, serum HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and alanine aminotransferase (ALT) were detected in 11 patients with AHB and 46 patients with CHB who were receiving anti?viral treatment, among whom 21 had primary treatment failure, 11 achieved virological response (VR) and 15 achieved VR and HBsAg seroclearance. The median IH cccDNA and tDNA levels in the patients with AHB (0.002 copies/cell and 0.04 copies/cell, respectively) were significantly lower than those in the patients with CHB. In the patients with CHB, the median IH cccDNA level among individuals who achieved VR and HBsAg seroclearance (0.012 copies/cell) was significantly lower than that in those who had failed primary treatment (4.18 copies/cell, P<0.0001) but not that in those who achieved solely VR (0.039 copies/cell, P=0.169). The median IH tDNA level in patients with CHB who achevied VR and HBsAg seroclearance (0.096 copies/cell) was significantly lower than that in those who failed primary treatment (371 copies/cell, P<0.0001) and those who achieved solely VR (1.62 copies/cell, P=0.001). No significant difference was observed in the area under the receiver operating characteristic (ROC) curve, which was used to predict the likelihood of achieving VR and HBsAg seroclearance, between IH tDNA and IH cccDNA levels (0.96 and 0.88, respectively; P>0.10). IH cccDNA levels were shown to be positively correlated with serum ALT (P=0.024), HBeAg (P=0.001) and IH tDNA levels (P<0.0001), but not with serum HBV DNA (P=0.12) and HBsAg levels in either HBeAg?positive (P=0.84) or in HBeAg?negative (P=0.146) patients. In conclusion, IH cccDNA may persist in patients with AHB and patients with CHB who acheive VR and HBsAg seroclearance following anti?viral treatment. Furthermore, IH cccDNA and tDNA may have potential in predicting successful therapeutic response in patients with CHB who receive anti?viral treatment. PMID:24566465

Ruan, Peng; Zhou, Boping; Dai, Xiufang; Sun, Zequn; Guo, Xiaoyan; Huang, Jian; Gong, Zuojiong

2014-04-01

339

Superoxide dismutase activity in rat brain during acute and chronic alcohol intoxication  

Microsoft Academic Search

The effect of acute and chronic ethanol administration on rat brain superoxide dismutase (SOD) activity was studied. Intraperitoneal injections of ethanol led to an inhibition of SOD activity. When ethanol was fed as the sole fluid, the SOD activity decreased progressively, reaching a plateau after 6 weeks of treatment. Withdrawal of ethanol produced a recovery of control values within 48

Marc Ledig; Jean-Rémy M'Paria; Paul Mandel

1981-01-01

340

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

341

Infectious mononucleosis complicated by acute hepatitis and myocarditis: a response to corticosteroids.  

PubMed

Infectious mononucleosis, or glandular fever, is a viral illness which commonly affects young adults. Symptoms can vary from sore throat, enlarged lymph glands, lethargy and weight loss to more serious clinical manifestations such as myocarditis or hepatitis. Treatment is usually conservative although there has been significant debate over the role of oral corticosteroids, especially in more serious cases. Evidence based medicine suggests that there is little to no role for steroids, but there are enough published case reports where steroid therapy has been potentially life saving that the debate continues. We present a case of a fit and well man who had significant multi-organ involvement secondary to infectious mononucleosis, and our experience of oral corticosteroid treatment. PMID:21686466

Ghosal, Robin; Lewis, Keir E; Chandramouli, Sriram

2009-01-01

342

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.

Ward, Christopher; Lee, Vincent

2014-01-01

343

Decrease of glutathione content in the prefrontal cortical mitochondria of rats with acute hepatic encephalopathy: prevention by histidine.  

PubMed

Mitochondrial glutathione (mGSH) is a critical factor in the cell defense against oxidative and nitrosative stress (ONS), and ONS is a key pathogenic event in hepatic encephalopathy (HE). Acute HE in the thioacetamide (TAA) model caused a 54 % decrease of mGSH content in the rat prefrontal cortex (pfc), but not in the striatum (str), nor did it affect the GSH content in the pfc or str homogenate. In the pfc, treatment with L- histidine (His), which is known to alleviate ONS-related symptoms in HE animals, attenuated the decrease of mGSH, and increased the GSH content in pfc and str homogenates and pfc microdialysates of control animals. His increased the expression of mRNA coding for the GSH synthesizing enzyme, glutamate cysteine ligase (GCL) and decreased that of the GSH-degrading enzyme ?-glutamyltranspeptidase (?GT). The results suggest that the decrease of mGSH may be an important contributing factor to mitochondrial dysfunction in HE, and delineate a new mechanistic aspect of the therapeutic potential of His in HE. PMID:23086200

Ruszkiewicz, Joanna; Fr??ko, Inez; Hilgier, Wojciech; Albrecht, Jan

2013-03-01

344

Does Hepatitis E Viral Load and Genotypes Influence the Final Outcome of Acute Liver Failure During Pregnancy?  

Microsoft Academic Search

BACKGROUND:Hepatitis E is a major health problem in developing countries including India. The incidence and mortality rate in pregnant women with fulminant hepatic failure (FHF) due to hepatitis E virus (HEV) has been reported to be significantly higher, specifically in Asian women. Pregnancy is usually associated with an altered status of sex steroid hormones and immunity. Steroid hormones directly influence

Premashis Kar; Nishat Jilani; Syed A. Husain; Sayed Tazeen Pasha; Ranjana Anand; Arvind Rai; Bhudev C. Das

2008-01-01

345

Chronic Alcohol Consumption Is a Major Risk Factor for Pancreatic Necrosis in Acute Pancreatitis  

Microsoft Academic Search

BACKGROUND:Much of the late morbidity and mortality of acute pancreatitis (AP) is attributed to complications of pancreatic necrosis (PNEC). Early diagnosis of PNEC in high-risk patients is critical to management. Hemoconcentration is one risk factor for PNEC, but additional risk factors are likely implicated.AIMS:(1) To evaluate a series of preselected clinical factors in a prospectively collected cohort with AP to

Georgios I. Papachristou; Dionysios J. Papachristou; Veronique D. Morinville; Adam Slivka; David C. Whitcomb

2006-01-01

346

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

347

The antioxidant activity of chondroitin-4-sulphate, in carbon tetrachloride-induced acute hepatitis in mice, involves NF-?B and caspase activation  

PubMed Central

Background and purpose: Reactive oxygen species (ROC) are the main causes of carbon tetrachloride (CCl4)-induced acute liver injury. Chondroitin-4-sulphate (C4S) is known to inhibit lipid peroxidation through antioxidant mechanisms. Activation of nuclear factor (NF)-?B and caspases may strongly intensify inflammation and cell damage, in addition to that directly exerted by ROS. We investigated whether treatment with C4S, besides exerting antioxidant activity, was able to modulate NF-?B and apoptosis activation in CCl4-induced liver injury in mice. Experimental approach: Acute hepatitis was induced in mice by an i.p. injection of CCl4. Varying doses of C4S were administered i.p. 1?h before, 6 and 12?h after CCl4 injection. 24?h after CCl4 injection, the mice were killed for biochemical and histological analysis. Key results: CCl4 injection produced: marked elevation of alanine aminotransferase and aspartate aminotransferase; hepatic membrane lipid peroxidation, assayed by 8-isoprostane levels; and depletion of reduced glutathione and superoxide dismutase. CCl4 also decreased NF-?B translocation and IkB?, and increased gene expression of mRNA and protein of metalloproteases (MMP)-2 and -9, and of pro- and cleaved forms of caspases-3 and -7. There was also increased liver polymorphonuclear infiltration, evaluated by elastase assay, and hepatic cell disruption. C4S treatment inhibited lipid peroxidation; blocked NF-?B activation and IkB? protein loss; decreased mRNA and proteins for MMPs and caspases; restored endogenous antioxidants; limited hepatic polymorphonuclear accumulation and tissue damage. Conclusions and implications: As antioxidants may inhibit NF-?B and caspase activation, we hypothesize that treatment with C4S was able to inhibit NF-?B and apoptosis activation in hepatic injury. PMID:18724385

Campo, G M; Avenoso, A; Campo, S; Nastasi, G; Traina, P; D'Ascola, A; Rugolo, C A; Calatroni, A

2008-01-01

348

Comparison between two high-dose methylprednisolone schedules in the treatment of acute hepatic cellular rejection in liver transplant recipients: a controlled clinical trial.  

PubMed

Intravenous methylprednisolone is used in most liver transplant centers as first-line therapy of acute hepatic cellular rejection in patients who undergo liver transplant. However, no controlled study has been performed to date to define the optimal dose and duration of the steroid regimen. The schedules that actually are used in most transplant centers are drawn from those that were developed empirically for the treatment of acute renal graft rejection. Thus, the aim of the study was to compare two schedules of steroid treatment of acute hepatic cellular rejection among those most widely used. Thirty-eight eligible patients with grade II or III acute hepatic cellular rejection were randomized to receive two different high-dose methylprednisolone schedules. Eighteen patients were randomized in group A (intravenous dose of 1,000 mg of methylprednisolone followed by a 6-day taper from 200 to 20 mg/d). Twenty patients were randomized in group B (intravenous dose of 1,000 mg of methylprednisolone for three consecutive days). The response to treatment was evaluated by means of a second liver biopsy. The treatment of group A proved to be more effective than treatment of group B. The resolution of acute hepatic cellular rejection was observed in 83.3% of cases in group A and 50.0% of cases in group B (P <.05). The treatment of group A proved to be safer also than treatment of group B. Patients randomized in group B showed a higher prevalence of infections (90.0% of cases versus 55.5% of cases; P <.01) mainly because of bacterial (80.0% versus 50.0%; P <.05) and viral (50.0% versus 16.6%; P <.05) agents. In conclusion, the study shows that intravenous administration of 1,000 mg of methylprednisolone followed by a 6-day taper from 200 to 20 mg/d is more effective and safer than intravenous dose of 1,000 mg of methylprednisolone for three consecutive days in the treatment of acute cellular rejection in patients with liver transplantation. PMID:12037783

Volpin, Roberta; Angeli, Paolo; Galioto, Alessandra; Fasolato, Silvano; Neri, Daniele; Barbazza, Franco; Merenda, Roberto; Del Piccolo, Franco; Strazzabosco, Mario; Casagrande, Fabio; Feltracco, Paolo; Sticca, Antonietta; Merkel, Carlo; Gerunda, Giorgio; Gatta, Angelo

2002-06-01

349

The inhibitory effect of black soybean on hepatic cholesterol accumulation in high cholesterol and high fat diet-induced non-alcoholic fatty liver disease.  

PubMed

Non-alcoholic fatty liver disease (NAFLD) is defined as excess of fat in the liver. We investigated the effects of black soybean on the cholesterol metabolism and insulin resistance of mice fed high cholesterol/fat diets. Mice were randomly allocated into four groups that were fed different diets: the normal cholesterol/fat diet; high cholesterol/fat diets (HCD); and HCD with 1%, and 4% black soybean powder (1B-HCD, and 4B-HCD). Liver total cholesterol and triglyceride concentrations were significantly lower in the black soybean-supplemented groups than that in the HCD group. PCR revealed significantly lower hepatic SREBP2 and HMG-CoA reductase mRNA levels of black soybean-supplemented mice. Real-time PCR revealed significantly higher hepatic ABCA1 mRNA level of black soybean-supplemented mice, which may increase cholesterol efflux. Liver bile acids concentration was significantly high in the 4B-HCD group. Black soybean stimulated secretion of adiponectin, activation of pAMPK, and eliminated free fatty acids in the liver. Black soybean supplementation decreased MDA and nitrate level. The activities of SOD, catalase, and GPx were restored by black soybean supplementation. Our data strongly indicate that black soybean influences the balance between oxidative and antioxidative stress. We suggest that black soybean improves cholesterol metabolism, insulin resistance, and alleviates oxidative damage in NAFLD. PMID:23900008

Jung, Ji-Hye; Kim, Hyun-Sook

2013-10-01

350

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.

Yu, Haoyong; Jia, Weiping; Guo, ZengKui

2014-01-01

351

Glucokinase links Kr?ppel-like factor 6 to the regulation of hepatic insulin sensitivity in non-alcoholic fatty liver disease  

PubMed Central

The polymorphism, KLF6-IVS1-27A, in the Krüppel-like factor 6 (KLF6) transcription factor gene enhances its splicing into antagonistic isoforms and is associated with delayed histological progression of non-alcoholic fatty liver disease (NAFLD). To explore a potential role for KLF6 in the development of insulin resistance, central to NAFLD pathogenesis, we genotyped KLF6-IVS1-27 in healthy subjects and assayed fasting plasma glucose (FPG) and insulin sensitivities. Furthermore, we quantified mRNA expression of KLF6 and glucokinase (GCK), as an important mediator of insulin sensitivity, in human livers and in liver tissues derived from a murine Klf6 knockdown model (DeltaKlf6). Klf6 overexpression studies in a mouse hepatocyte line were utilized to mechanistically link KLF6 with Gck promoter activity. Results KLF6-IVS1-27Gwt (ie., less KLF6 splicing) was associated with stepwise increases in FPG and insulin and reduced hepatic insulin sensitivity. KLF6 binds to the liver-specific Gck promoter and activates a GCK promoter-reporter, identifying GCK as a KLF6 direct transcriptional target. Accordingly, in DeltaKlf6 hepatocytes, Gck expression was reduced and stable transfection of Klf6 led to upregulation of Gck. GCK and KLF6 mRNAs correlate directly in human NAFLD tissues and immunohistochemistry studies confirm falling levels of both KLF6 and GCK in fat laden hepatocytes. In contrast to full length KLF6, splice variant KLF6-SV1 increases in NAFLD hepatocytes and inversely correlates with glucokinase regulatory protein, which negatively regulates GCK activity. Conclusion KLF6 regulation of GCK contributes to the development of hepatic insulin resistance. The KLF6-IVS1-27A polymorphism, which generates more KLF6-SV1, combats this, lowering hepatic insulin resistance and blood glucose. PMID:22095588

Bechmann, Lars P; Gastaldelli, Amalia; Vetter, Diana; Patman, Gillian L; Pascoe, Laura; Hannivoort, Rebekka A; Lee, Ursula E; Fiel, Isabel; Munoz, Ursula; Ciociaro, Demetrio; Lee, Young-Min; Buzzigoli, Emma; Miele, Luca; Hui, Kei Y; Bugianesi, Elisabetta; Burt, Alastair D; Day, Christopher P; Mari, Andrea; Agius, Loranne; Walker, Mark; Friedman, Scott L; Reeves, Helen L

2011-01-01

352

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

PubMed

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

353

SOCS3 expression correlates with severity of inflammation in mouse hepatitis virus strain 3-induced acute liver failure and HBV-ACLF.  

PubMed

Recently, suppressor of cytokine signaling-3 (SOCS3) has been shown to be an inducible endogenous negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway which is relevant in inflammatory response, while its functions in acute liver failure and HBV-induced acute-on-chronic liver failure (HBV-ACLF) have not been fully elucidated. In this study, we explored the role of SOCS3 in the development of mouse hepatitis virus strain 3 (MHV-3)-induced acute liver failure and its expression in liver and peripheral blood mononuclear cells (PBMCs) of patients with HBV-ACLF. Inflammation-related gene expression was detected by real-time PCR, immunohistochemistry and Western blotting. The correlation between SOCS3 level and liver injury was studied. Our results showed that the SOCS3 expression was significantly elevated in both the liver tissue and PBMCs from patients with HBV-ACLF compared to mild chronic hepatitis B (CHB). Moreover, a time course study showed that SOCS3 level was increased remarkably in the liver of BALB/cJ mice at 72 h post-infection. Pro-inflammatory cytokines, interleukin (IL)-1?, IL-6, and tumor necrosis factor (TNF)-?, were also increased significantly at 72 h post-infection. There was a close correlation between hepatic SOCS3 level and IL-6, and the severity of liver injury defined by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, respectively. These data suggested that SOCS3 may play a pivotal role in the pathogenesis of MHV-3-induced acute liver failure and HBV-ACLF. PMID:24939297

Li, Yong; Han, Mei-fang; Li, Wei-na; Shi, Ai-chao; Zhang, Yuan-ya; Wang, Hong-yan; Wang, Fa-xi; Li, Lan; Wu, Ting; Ding, Lin; Chen, Tao; Yan, Wei-ming; Luo, Xiao-ping; Ning, Qin

2014-06-01

354

Indirect Effects of Acute Alcohol Intoxication on Sexual Risk-taking: The Roles of Subjective and Physiological Sexual Arousal  

Microsoft Academic Search

Three experiments supported the idea that alcohol fosters sexual risk-taking in men and women, in part, through its effects\\u000a on sexual arousal. In Experiment 1, increasing alcohol dosage (target blood alcohol levels of .00, .04, .08%) heightened men’s\\u000a and women’s risk-taking intentions. Alcohol’s effect was indirect via increased subjective sexual arousal; also, men exhibited\\u000a greater risk-taking than women. In Experiment

William H. George; Kelly Cue Davis; Jeanette Norris; Julia R. Heiman; Susan A. Stoner; Rebecca L. Schacht; Christian S. Hendershot; Kelly F. Kajumulo

2009-01-01

355

Acute Central Neuropeptide Y Administration Increases Food Intake but Does Not Affect Hepatic Very Low-Density Lipoprotein (Vldl) Production in Mice  

PubMed Central

Objective Central neuropeptide Y (NPY) administration stimulates food intake in rodents. In addition, acute modulation of central NPY signaling increases hepatic production of very low-density lipoprotein (VLDL)-triglyceride (TG) in rats. As hypertriglyceridemia is an important risk factor for atherosclerosis, for which well-established mouse models are available, we set out to validate the effect of NPY on hepatic VLDL-TG production in mice, to ultimately investigate whether NPY, by increasing VLDL production, contributes to the development of atherosclerosis. Research Design and Methods Male C57Bl/6J mice received an intracerebroventricular (i.c.v.) cannula into the lateral (LV) or third (3V) ventricle of the brain. One week later, after a 4 h fast, the animals received an intravenous (i.v.) injection of Tran35S (100 µCi) followed by tyloxapol (500 mg/kg body weight; BW), enabling the study of hepatic VLDL-apoB and VLDL-TG production, respectively. Immediately after the i.v. injection of tyloxapol, the animals received either an i.c.v. injection of NPY (0.2 mg/kg BW in artificial cerebrospinal fluid; aCSF), synthetic Y1 receptor antagonist GR231118 (0.5 mg/kg BW in aCSF) or vehicle (aCSF), or an i.v. injection of PYY3–36 (0.5 mg/kg BW in PBS) or vehicle (PBS). Results Administration of NPY into both the LV and 3V increased food intake within one hour after injection (+164%, p<0.001 and +367%, p<0.001, respectively). NPY administration neither in the LV nor in the 3V affected hepatic VLDL-TG or VLDL-apoB production. Likewise, antagonizing central NPY signaling by either PYY3–36 or GR231118 administration did not affect hepatic VLDL production. Conclusion In mice, as opposed to rats, acute central administration of NPY increases food intake without affecting hepatic VLDL production. These results are of great significance when extrapolating findings on the central regulation of hepatic VLDL production between species. PMID:23460782

Havekes, Louis M.; Romijn, Johannes A.; Rensen, Patrick C. N.

2013-01-01

356

Cost-effective Screening for Acute Hepatitis C Virus Infection in HIV-Infected Men Who Have Sex With Men  

PubMed Central

Background.?We used a Monte Carlo computer simulation to estimate the effectiveness and cost-effectiveness of screening for acute hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)–infected men who have sex with men. Methods.?One-time screening for prevalent HCV infection was performed at the time of enrollment in care, followed by either symptom-based screening, screening with liver function tests (LFTs), HCV antibody (Ab) screening, or HCV RNA screening in various combinations and intervals. We considered both treatment with pegylated interferon and ribavirin (PEG/RBV) alone and with an HCV protease inhibitor. Outcome measures were life expectancy, quality-adjusted life expectancy, direct medical costs, and cost-effectiveness, assuming a societal willingness to pay $100 000 per quality-adjusted life-year (QALY) gained. Results.?All strategies increased life expectancy (from 0.49 to 0.94 life-months), quality-adjusted life expectancy (from 0.47 to 1.00 quality-adjusted life-months), and costs (from $1900 to $7600), compared with symptom-based screening. The incremental cost-effectiveness ratio of screening with 6-month LFTs and a 12-month HCV Ab test, compared with symptom-based screening, was $43 700/QALY (for PEG/RBV alone) and $57 800/QALY (for PEG/RBV plus HCV protease inhibitor). The incremental cost-effectiveness ratio of screening with 3-month LFTs, compared with 6-month LFTs plus a 12-month HCV Ab test, was $129 700/QALY (for PEG/RBV alone) and $229 900/QALY (for PEG/RBV plus HCV protease inhibitor). With HCV protease inhibitor–based therapy, screening with 6-month LFTs and a 12-month HCV Ab test was the optimal strategy when the HCV infection incidence was ?1.25 cases/100 person-years. The 3-month LFT strategy was optimal when the incidence was >1.25 cases/100 person-years. Conclusions.?Screening for acute HCV infection in HIV-infected MSM prolongs life expectancy and is cost-effective. Depending on incidence, regular screening with LFTs, with or without an HCV Ab test, is the optimal strategy. PMID:22491339

Linas, Benjamin P.; Wong, Angela Y.; Schackman, Bruce R.; Kim, Arthur Y.; Freedberg, Kenneth A.

2012-01-01

357

Acute exposure to 3-methylcholanthrene induces hepatic oxidative stress via activation of the Nrf2/ARE signaling pathway in mice.  

PubMed

Polycyclic aromatic hydrocarbons (PAHs) are the most common contaminants in the environment. The primary focus on the toxicity of PAHs is their ability to activate the aryl hydrocarbon receptor (AhR)-mediated pathway and lead to carcinogenesis in different organisms. However, the influence of PAHs on the antioxidant system in mammalian systems has received only limited attention. In the present study, we observed that the intraperitoneal injection of 100 mg/kg 3-methylcholanthrene (3MC) into mice significantly increased reactive oxygen species (ROS) levels and malondialdehyde (MDA) contents and decreased glutathione (GSH) contents and the activity of total antioxidant capacity (T-AOC), indicating that serious oxidative stress had been induced in the liver of mice. Then, the oxidative stress signal activated the nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathway by enhancing the mRNA levels of Nrf2, p38, and Erk2. Moreover, the mRNA levels of Nrf2/ARE target genes, including glutathione peroxidase (Gpx), glutathione reductase (GR), glutathione synthetase (GS), NAD(P)H: quinone oxidoreductase 1 (Nqo1), superoxide dismutase 1 (Sod1), and Sod2, increased significantly after treatment with 3MC for 24 hours. The hepatic levels of NQO1 and the activities of GR and GS were also significantly enhanced at 24 hours after 3MC treatment. Because the expression of NQO1 is co-regulated by Nrf2/ARE and AhR/XRE in mammalian tissues, NQO1 may play an important role in protecting against the oxidative stress induced by 3MC. Taken together, our findings suggested that acute exposure to 3MC altered the cellular redox balance in hepatocytes to trigger Nrf2-regulated antioxidant responses, which may represent an adaptive cell defense mechanism against the oxidative stress induced by PAHs. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1399-1408, 2014. PMID:23712962

Jin, Yuanxiang; Miao, Wenyu; Lin, Xiaojian; Pan, Xiuhong; Ye, Yang; Xu, Minjie; Fu, Zhengwei

2014-12-01

358

Preliminary characterization, antioxidant activity in vitro and hepatoprotective effect on acute alcohol-induced liver injury in mice of polysaccharides from the peduncles of Hovenia dulcis.  

PubMed

The fresh fleshy peduncles of Hovenia dulcis have been used as a food supplement and traditional herbal medicine for the treatment of liver diseases and alcoholic poisoning for more than a millennium. The objectives of the present study, therefore, were to determine the antioxidant activity of polysaccharides from the peduncles of H. dulcis (HDPS) and to evaluate its hepatoprotective effect on acute alcohol-induced liver injury in mice. HDPS, prepared by hot water extraction, ethanol precipitation and treatment of macroporous resin, was found to be non-starch polysaccharide and mainly composed of galactose, arabinose, rhamnose and galacturonic acid. In in vitro antioxidant assay, HDPS exhibited high superoxide radical scavenging activity, strong inhibition effect on lipid peroxidation and a medium ferrous ion-chelating activity. For hepatoprotective activity in vivo, the administration of HDPS significantly decreased the serum levels of alanine aminotransferase and aspartate aminotransferase, significantly decreased the liver level of malondialdehyde and remarkably restored the liver activities of superoxide dismutase and glutathione peroxidase in alcohol-induced liver injury mice. The results suggested that HDPS had a significant protective effect against acute alcohol-induced liver injury possibly via its antioxidant activity to protect biological systems against the oxidative stress. PMID:22750723

Wang, Mingchun; Zhu, Peilei; Jiang, Changxing; Ma, Liping; Zhang, Zhanjun; Zeng, Xiaoxiong

2012-09-01

359

Alcoholic lung injury: metabolic, biochemical and immunological aspects.  

PubMed

Chronic alcohol abuse is a systemic disorder and a risk factor for acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD). A significant amount of ingested alcohol reaches airway passages in the lungs and can be metabolized via oxidative and non-oxidative pathways. About 90% of the ingested alcohol is metabolized via hepatic alcohol dehydrogenase (ADH)-catalyzed oxidative pathway. Alcohol can also be metabolized by cytochrome P450 2E1 (CYP2E1), particularly during chronic alcohol abuse. Both the oxidative pathways, however, are associated with oxidative stress due to the formation of acetaldehyde and/or reactive oxygen species (ROS). Alcohol ingestion is also known to cause endoplasmic reticulum (ER) stress, which can be mediated by oxidative and/or non-oxidative metabolites of ethanol. An acute as well as chronic alcohol ingestions impair protective antioxidants, oxidize reduced glutathione (GSH, cellular antioxidant against ROS and oxidative stress), and suppress innate and adaptive immunity in the lungs. Oxidative stress and suppressed immunity in the lungs of chronic alcohol abusers collectively are considered to be major risk factors for infection and development of pneumonia, and such diseases as ARDS and COPD. Prior human and experimental studies attempted to identify common mechanisms by which alcohol abuse directly causes toxicity to alveolar epithelium and respiratory tract, particularly lungs. In this review, the metabolic basis of lung injury, oxidative and ER stress and immunosuppression in experimental models and alcoholic patients, as well as potential immunomodulatory therapeutic strategies for improving host defenses against alcohol-induced pulmonary infections are discussed. PMID:23892124

Kaphalia, Lata; Calhoun, William J

2013-10-24

360

Alcoholic Lung Injury: Metabolic, Biochemical and Immunological Aspects  

PubMed Central

Chronic alcohol abuse is a systemic disorder and a risk factor for acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD). A significant amount of ingested alcohol reaches airway passages in the lungs and can be metabolized via oxidative and non-oxidative pathways. About 90% of the ingested alcohol is metabolized via hepatic alcohol dehydrogenase (ADH)-catalyzed oxidative pathway. Alcohol can also be metabolized by cytochrome P450 2E1 (CYP2E1), particularly during chronic alcohol abuse. Both the oxidative pathways, however, are associated with oxidative stress due to the formation of acetaldehyde and/or reactive oxygen species (ROS). Alcohol ingestion is also known to cause endoplasmic reticulum (ER) stress, which can be mediated by oxidative and/or non-oxidative metabolites of ethanol. An acute as well as chronic alcohol ingestions impair protective antioxidants, oxidize reduced glutathione (GSH, cellular antioxidant against ROS and oxidative stress), and suppress innate and adaptive immunity in the lungs. Oxidative stress and suppressed immunity in the lungs of chronic alcohol abusers collectively are considered to be major risk factors for infection and development of pneumonia, and such diseases as ARDS and COPD. Prior human and experimental studies attempted to identify common mechanisms by which alcohol abuse directly causes toxicity to alveolar epithelium and respiratory tract, particularly lungs. In this review, the metabolic basis of lung injury, oxidative and ER stress and immunosuppression in experimental models and alcoholic patients, as well as potential immunomodulatory therapeutic strategies for improving host defenses against alcohol-induced pulmonary infections are discussed. PMID:23892124

Kaphalia, Lata; Calhoun, William J.

2013-01-01

361

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

362

Acute renal failure, thrombocytopenia, and elevated liver enzymes after concurrent abuse of alcohol and cocaine  

PubMed Central

Cocaine has been associated with known adverse effects on cardiac, cerebrovascular and pulmonary systems. However, the effect of cocaine on other organs has not been extensively reported. A middle age man presented with abdominal pain and nausea after inhalation of crack cocaine. On admission, he was found to be hypertensive and tachycardic. Physical examination revealed mild abdominal tenderness without rebound. Laboratory investigations were significant for acute kidney failure with elevated serum creatinine (3.72 mg/dL), thrombocytopenia (platelet count 74,000/UL), elevated alanine and aspartate transaminases (ALT 331 U/L; AST 462 U/L) and elevated creatine phosphokinase (CPK 5885 U/L). Urine toxicology screening solely revealed cocaine. A clinical diagnosis of cocaine toxicity was made and patient was admitted to the intensive care unit because of multi organ failure. Despite downward trending of liver enzymes during the hospital course, he continued to have residual renal insufficiency and a low platelet count at the time of discharge. In a patient with history of recent cocaine use presenting with these manifestations, cocaine itself should be considered as a likely cause. PMID:24765297

Hosseinnezhad, Alireza; Vijayakrishnan, Rajakrishnan; Farmer, Mary Jo S.

2011-01-01

363

Interferon ?-Stimulated Natural Killer Cells From Patients With Acute Hepatitis C Virus (HCV) Infection Recognize HCV-Infected and Uninfected Hepatoma Cells via DNAX accessory molecule-1  

PubMed Central

Background.?Natural killer (NK) cells are an important component of the innate immune defense against viruses, including hepatitis C virus (HCV). The cell culture system using HCV-permissive Huh-7.5 cells make studies on interaction of NK cells and HCV-infected target cells possible. We used this system to characterize interactions of HCV-infected Huh-7.5 cells and NK cells from healthy controls and patients with acute HCV infection. Methods.?IFN?- and IL-2 stimulated NK cells were cultured with HCV-infected hepatoma cells and subsequently analyzed (for degranulation and cytokine production) via multicolour flow cytometry. Luciferase assyas have been used to study inhibition of HCV replication. Further, PBMC from patients with acute hepatitis C as well as HCV-infected Huh7.5 cells have been analyzed via flow cytometry for expression of NK cell receptors and ligands, respectively. Results.?After interferon (IFN) ? stimulation, NK cells from healthy controls and patients with acute hepatitis C efficiently recognized both HCV-infected and uninfected hepatoma cells. Subsequent dissection of receptor-ligand interaction revealed a dominant role for DNAM-1 and a complementary contribution of NKG2D for NK cell activation in this setting. Furthermore, IFN-?–stimulated NK cells effectively inhibited HCV replication in a DNAM-1–dependent manner. Conclusions.?Human NK cells recognize HCV-infected hepatoma cells after IFN-? stimulation in a DNAM-1–dependent manner. Furthermore, interaction of IFN-?–stimulated NK cells with HCV-infected hepatoma cells efficiently reduced HCV replication. This study opens up future studies of NK cell interaction with HCV-infected hepatocytes to gain further insight into the pathogenesis of human HCV infection and the therapeutic effects of IFN-?. PMID:22457290

Stegmann, Kerstin A.; Bjorkstrom, Niklas K.; Ciesek, Sandra; Lunemann, Sebastian; Jaroszewicz, Jerzy; Wiegand, Johannes; Malinski, Phillipp; Dustin, Lynn B.; Rice, Charles M.; Manns, Michael P.; Pietschmann, Thomas; Cornberg, Markus; Ljunggren, Hans-Gustaf

2012-01-01

364

Seroprevalence of Human Herpes Simplex, Hepatitis B and Epstein-Barr Viruses in Children with Acute Lymphoblastic Leukemia in Southern Iran  

Microsoft Academic Search

To investigate the seroprevalence of Herpes Simplex Viruses (HSV1 and HSV2), Ebstein-Barr Virus (EBV) and Hepatitis B Virus\\u000a (HBV) in children with acute lymphoblastic leukemia (ALL) in southern Iran. 90 patients with ALL and 90 age-sex matched healthy\\u000a participants were enrolled in this study. Antibodies (IgG) against HBsAg, HSV1, HSV2, EBV different antigens including Epstein-Barr\\u000a nuclear antigen-1 (EBNA-1), viral capsid

Seyed Babak Mahjour; Fariborz Ghaffarpasand; Mohammad Javad Fattahi; Abbas Ghaderi; Alireza Fotouhi Ghiam; Mehran Karimi

2010-01-01

365

Novel molecular alterations in the ORF 2 capsid gene of hepatitis E virus in patients with acute liver failure in North India.  

PubMed

Hepatitis E virus (HEV) is evolving as a major global threat to public health, including in developed countries. We partially sequenced the ORF 2 capsid protein genes of HEV genomes from patients with acute liver failure, including pregnant women in the northern part of India. Five unique synonymous substitutions and one non-synonymous substitution, along with a novel mutation, P259S, in the capsid gene, were identified that might be associated with the poor outcome in the patients. Phylogenetic analysis revealed that the isolates belonged to genotype 1 with subtype 1a. The significance of these findings for disease pathogenicity needs to be investigated further. PMID:25100237

Borkakoti, Jayanta; Ahmed, Giasuddin; Hussain, Syed Akhtar; Rai, Arvind; Kar, Premashis

2014-12-01

366

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

367

Hepadna virus nucleocapsid and surface antigens and the antigen-specific antibodies associated with hepatocyte plasma membranes in experimental woodchuck acute hepatitis.  

PubMed

Hepatocyte plasma membranes purified from five woodchucks with distinct serologic and histologic patterns of experimentally induced acute woodchuck hepatitis virus (WHV) infection were studied to determine the virus antigens expression and anti-viral specificity of the bound immunoglobulins. WHV core, e, and surface antigens (WHcAg, WHeAg, and WHsAg, respectively) were analyzed with the use of immunoblotting technique both in the native form of these membranes and in the membranes treated with high molar urea or a nonionic detergent. The eluted material was tested either for the presence of WHV antigens or reactivity of the antibodies directed to the virus antigens. The data revealed that acute WHV infection is accompanied by hepatocyte plasma membrane expression of all three viral antigens tested. In all cases, native membranes displayed both WHeAg and WHsAg, whereas WHcAg presence was detected in hepatocyte plasma membranes after their disruption with urea or a detergent. The data indicated that a part or, in some instances, even the whole detectable WHcAg specificity can be incorporated into plasma membrane structure in such a way that it is not accessible for recognition by the specific antibodies (anti-WHc), suggesting at least a partial functional disability of this antigen as a target for immunologic reactions in in vivo conditions. In contrast, WHeAg specificity was detectable in all native membrane preparations studied and its expression was not evidently influenced by the employed treatments, whereas that of WHsAg tended to decline. Further, anti-WHc reactivity was identified in all membrane eluates tested, but antibodies to WHeAg (anti-WHe) were exclusively found in the material eluted from membranes originating from woodchucks with borderline histologic activity of acute hepatitis, which cleared away e antigen from the serum shortly before liver perfusion. Antibodies to WHsAg (anti-WHs) did not show up in the eluates. The present findings demonstrated that WHeAg specificity is not only exposed on the surface of infected hepatocytes, but is also relatively more easily accessible for serologic recognition than that of WHcAg in acute WHV infection. The above observation suggests that e antigen can serve as a potential plasma membrane target for hepatocytolytic attack in addition to that of WHsAg or WHcAg. Moreover, the results of this study demonstrated an apparent relationship between low histologic activity of liver inflammation, e antigen clearance from the circulation, and detectability of hepatocyte plasma membrane-bound anti-e antibodies in acute hepadna viral hepatitis. PMID:2359258

Michalak, T I; Lin, B; Churchill, N D; Dzwonkowski, P; Desousa, J R

1990-06-01

368

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

369

Using Human Adipose Tissue-Derived Mesenchymal Stem Cells as Salvage Therapy for Hepatic Graft-Versus-Host Disease Resembling Acute Hepatitis  

Microsoft Academic Search

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

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

2007-01-01

370

Curative Effects of Thiacremonone against Acetaminophen-Induced Acute Hepatic Failure via Inhibition of Proinflammatory Cytokines Production and Infiltration of Cytotoxic Immune Cells and Kupffer Cells  

PubMed Central

High doses of acetaminophen (APAP; N-acetyl-p-aminophenol) cause severe hepatotoxicity after metabolic activation by cytochrome P450 2E1. This study was undertaken to examine the preventive effects of thiacremonone, a compound extracted from garlic, on APAP-induced acute hepatic failure in male C57BL/6J. Mice received with 500?mg/kg APAP after a 7-day pretreatment with thiacremonone (10–50?mg/kg). Thiacremonone inhibited the APAP-induced serum ALT and AST levels in a dose-dependent manner, and markedly reduced the restricted area of necrosis and inflammation by administration of APAP. Thiacremonone also inhibited the APAP-induced depletion of intracellular GSH, induction of nitric oxide, and lipid peroxidation as well as expression of P450 2E1. After APAP injection, the numbers of Kupffer cells, natural killer cells, and cytotoxic T cells were elevated, but the elevated cell numbers in the liver were reduced in thiacremonone pretreated mice. The expression levels of I-309, M-CSF, MIG, MIP-1?, MIP-1?, IL-7, and IL-17 were increased by APAP treatment, which were inhibited in thiacremonone pretreated mice. These data indicate that thiacremonone could be a useful agent for the treatment of drug-induced hepatic failure and that the reduction of cytotoxic immune cells as well as proinflammatory cytokine production may be critical for the prevention of APAP-induced acute liver toxicity. PMID:23935693

Kim, Yu Ri; Ban, Jung Ok; Yoo, Hwan Soo; Lee, Yong Moon; Yoon, Yeo Pyo; Eum, So Young; Jeong, Heon Sang; Yoon, Do-young; Han, Sang Bae; Hong, Jin Tae

2013-01-01

371

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

372

Trouble with Bleeding: Risk Factors for Acute Hepatitis C among HIV-Positive Gay Men from Germany--A Case-Control Study  

PubMed Central

Objectives To identify risk factors for hepatitis C among HIV-positive men who have sex with men (MSM), focusing on potential sexual, nosocomial, and other non-sexual determinants. Background Outbreaks of hepatitis C virus (HCV) infections among HIV-positive MSM have been reported by clinicians in post-industrialized countries since 2000. The sexual acquisition of HCV by gay men who are HIV positive is not, however, fully understood. Methods Between 2006 and 2008, a case-control study was embedded into a behavioural survey of MSM in Germany. Cases were HIV-positive and acutely HCV-co-infected, with no history of injection drug use. HIV-positive MSM without known HCV infection, matched for age group, served as controls. The HCV-serostatus of controls was assessed by serological testing of dried blood specimens. Univariable and multivariable regression analyses were used to identify factors independently associated with HCV-co-infection. Results 34 cases and 67 controls were included. Sex-associated rectal bleeding, receptive fisting and snorting cocaine/amphetamines, combined with group sex, were independently associated with case status. Among cases, surgical interventions overlapped with sex-associated rectal bleeding. Conclusions Sexual practices leading to rectal bleeding, and snorting drugs in settings of increased HCV-prevalence are risk factors for acute hepatitis C. We suggest that sharing snorting equipment as well as sharing sexual partners might be modes of sexual transmission. Condoms and gloves may not provide adequate protection if they are contaminated with blood. Public health interventions for HIV-positive gay men should address the role of blood in sexual risk behaviour. Further research is needed into the interplay of proctosurgery and sex-associated rectal bleeding. PMID:21408083

Schmidt, Axel J.; Rockstroh, Jurgen K.; Vogel, Martin; An der Heiden, Matthias; Baillot, Armin; Krznaric, Ivanka; Radun, Doris

2011-01-01

373

Alcohol-Related Diarrhea  

Microsoft Academic Search

\\u000a Diarrhea related to alcohol abuse may be either acute or chronic. Acute diarrheas are the result of dietary indiscretion,\\u000a transient anatomic or motility changes of the stomach or small intestine, impaired nutrient absorption, mucosal barrier function\\u000a or pancreatic secretion as well as hormonal\\/cytokine abnormalities related to alcohol hangover. Chronic diarrheas may result\\u000a from alcohol withdrawal, pancreatic or hepatobiliary dysfunction, morphologic

Nischita K. Reddy; Ashwani Singal; Don W. Powell

374