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Sample records for alcoholic hepatitis ah

  1. Alcoholic hepatitis.

    PubMed

    Damgaard Sandahl, Thomas

    2014-10-01

    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

  2. Symptoms and signs of acute alcoholic hepatitis

    PubMed Central

    Basra, Gurjot; Basra, Sarpreet; Parupudi, Sreeram

    2011-01-01

    Although there is not one specific sign or symptom related to alcoholic hepatitis (AH), a constellation of symptoms and signs can help make the diagnosis of AH with reasonable accuracy. Documentation of chronic and active alcohol abuse is paramount in making a diagnosis of AH. Clinical presentation after abstinence for more than 3 m should raise doubts about the diagnosis of AH and dictate the need for considering other causes of liver disease, decompensation of alcoholic cirrhosis, sepsis and malignancy as the cause of patient’s clinical profile. PMID:21731904

  3. Update on Alcoholic Hepatitis.

    PubMed

    Torok, Natalie J

    2015-11-02

    Alcoholic liver disease is one of the most prevalent liver diseases worldwide, and a major cause of morbidity and mortality. Alcoholic hepatitis is a severe form of liver injury in patients with alcohol abuse, can present as an acute on chronic liver failure associated with a rapid decline in liver synthetic function, and consequent increase in mortality. Despite therapy, about 30%-50% of patients with severe alcoholic hepatitis eventually die. The pathogenic pathways that lead to the development of alcoholic hepatitis are complex and involve oxidative stress, gut dysbiosis, and dysregulation of the innate and adaptive immune system with injury to the parenchymal cells and activation of hepatic stellate cells. As accepted treatment approaches are currently limited, a better understanding of the pathophysiology would be required to generate new approaches that improve outcomes. This review focuses on recent advances in the diagnosis, pathogenesis of alcoholic hepatitis and novel treatment strategies.

  4. Update on Alcoholic Hepatitis

    PubMed Central

    Torok, Natalie J.

    2015-01-01

    Alcoholic liver disease is one of the most prevalent liver diseases worldwide, and a major cause of morbidity and mortality. Alcoholic hepatitis is a severe form of liver injury in patients with alcohol abuse, can present as an acute on chronic liver failure associated with a rapid decline in liver synthetic function, and consequent increase in mortality. Despite therapy, about 30%–50% of patients with severe alcoholic hepatitis eventually die. The pathogenic pathways that lead to the development of alcoholic hepatitis are complex and involve oxidative stress, gut dysbiosis, and dysregulation of the innate and adaptive immune system with injury to the parenchymal cells and activation of hepatic stellate cells. As accepted treatment approaches are currently limited, a better understanding of the pathophysiology would be required to generate new approaches that improve outcomes. This review focuses on recent advances in the diagnosis, pathogenesis of alcoholic hepatitis and novel treatment strategies. PMID:26540078

  5. Definition, epidemiology and magnitude of alcoholic hepatitis

    PubMed Central

    Basra, Sarpreet; Anand, Bhupinderjit S

    2011-01-01

    Alcoholic liver disease (ALD) is a major cause of alcohol-related morbidity and mortality. Its presentation ranges from fatty liver to alcoholic hepatitis (AH), cirrhosis, and hepatocellular carcinoma. Although the amount and pattern of alcohol consumption is a well recognized predisposing factor for the development of serious liver pathology, environmental factors and the host’s genetic make-up may also play significant roles that have not yet been entirely explored. Continuing alcohol consumption is a major factor that influences the survival of patients with AH. The presence of cirrhosis at presentation or its development on follow up is a major factor determining the outcome in the long run. This chapter deals with the epidemiology and magnitude of ALD in general and AH in particular. PMID:21731902

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

    SciTech Connect

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

    1984-01-01

    This study was designed to identify abnormalities in the hepatic-arterial/portal-venous scintiangiogram (SA) in alcoholic hepatitis (AH). SA's were performed in 35 patients with acute alcoholic hepatitis (AAH), 8; acute alcoholic hepatitis superimposed on cirrhosis (A/C), 14; and cirrhosis (C), 13. Posterior flows were done with a bolus of 10 mCi Tc-99m sulfur colloid with computer time-activity curves over the liver and left kidney. Curves were analyzed for per cent of hepatic arterial (HA) and portal venous contribution using the slope ratio method. Hepatic arterialization was estimated from the angle of the HA component of the curve. Reversal of the relative contribution of the hepatic and portal components of total flow were seen in all groups. Although quite severe in AH, the degree of reversal could not be used to differentiate among the groups. The average HA angle in AAH was 48.3 +- 8.1, in A/C 41.5 +- 10.6, and in C 30.4 +- 12.1. In reviewing the data of only those in the acute clinical phase of AH and not the recovery phase (1 AAH, 3 A/C) and those without other causes of alteration in hepatic arterialization (1 hepatoma, 1 portalcaval shunt, 6 renal failure), the average HA angle in AAH was 50.1 +- 6.6, 45.4 +- 8.2 in A/C, and 23.2 +- 4.2 in C. In 6 with renal failure (2 C, 2AAH, 2 A/C) the HA angle ws 52.7 +- 5.7. In all cases cirrhosis could be differentiated from both A/C (P=.05) and AAH (P<.01) using the HA angle. In absence of renal failure, portal shunt, or hepatoma, P was <.01 in both comparisons.

  7. Pharmacotherapy of acute alcoholic hepatitis in clinical practice

    PubMed Central

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

    2014-01-01

    Severe alcoholic hepatitis (AH) is an acute form of alcohol induced liver disease with a poor prognosis that is seen in the patients who consume large quantities of alcohol. The diagnosis of AH is based on the appropriate alcohol intake history and is supported with clinical and histological features, and several scoring systems. Glucocorticoids are the mainstay for treating severe AH with pentoxifylline used as an alternative to steroids in addition to total alcohol abstinence. Liver transplantation is a possible therapeutic option for severe AH. Among the anti-craving medications able to improve abstinence rate, baclofen seems to be effective and safe in the alcoholic patients affected by severe liver damage. PMID:24605014

  8. Therapeutic Strategies for the Treatment of Alcoholic Hepatitis.

    PubMed

    Singal, Ashwani K; Shah, Vijay H

    2016-02-01

    Acute alcoholic hepatitis is a unique clinical syndrome among patients with chronic and active heavy alcohol use. Presenting with acute or chronic liver failure, a severe episode has a potential for 30 to 40% mortality at 1 month from presentation, if not recognized and left untreated. Alcoholic hepatitis patients need supportive therapy for abstinence and nutritional supplementation for those patients with markedly reduced caloric intake. Results of the recently published STOPAH (Steroids or Pentoxifylline for Alcoholic Hepatitis) Study showed only a benefit of corticosteroids on short-term mortality without any benefit of pentoxifylline. Neither of these two drugs impacts medium- and long-term mortality, which is mainly driven by abstinence from alcohol. With the emerging data on the benefits of liver transplantation, liver transplantation could be an important salvage option for a very highly select group of AH patients. More data are needed on the use of liver transplantation in AH as the basis for deriving protocols for selecting cases and for posttransplant management. Currently, many clinical trials are examining the efficacy and safety of new or repurposed compounds in severe AH. These drugs are targeted at various pathways in the pathogenesis of AH: the gut-liver axis, the inflammatory cascade, and liver injury. With increasing interest of researchers and clinicians, supported by funding from the National Institute on Alcohol Abuse and Alcoholism, the future seems promising for the development of effective and safe pharmacological interventions for severe AH. PMID:26870933

  9. Alcoholic hepatitis: The pivotal role of Kupffer cells

    PubMed Central

    Suraweera, Duminda B; Weeratunga, Ashley N; Hu, Robert W; Pandol, Stephen J; Hu, Richard

    2015-01-01

    Kupffer cells play a central role in the pathogenesis of alcoholic hepatitis (AH). It is believed that alcohol increases the gut permeability that results in raised levels of serum endotoxins containing lipopolysaccharides (LPS). LPS binds to LPS-binding proteins and presents it to a membrane glycoprotein called CD14, which then activates Kupffer cells via a receptor called toll-like receptor 4. This endotoxin mediated activation of Kupffer cells plays an important role in the inflammatory process resulting in alcoholic hepatitis. There is no effective treatment for AH, although notable progress has been made over the last decade in understanding the underlying mechanism of alcoholic hepatitis. We specifically review the current research on the role of Kupffer cells in the pathogenesis of AH and the treatment strategies. We suggest that the imbalance between the pro-inflammatory and the anti-inflammatory process as well as the increased production of reactive oxygen species eventually lead to hepatocyte injury, the final event of alcoholic hepatitis. PMID:26600966

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

    PubMed

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

    2014-12-01

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

  11. Current Management of Alcoholic Hepatitis and Future Therapies

    PubMed Central

    Saberi, Behnam; Dadabhai, Alia S.; Jang, Yoon-Young; Gurakar, Ahmet; Mezey, Esteban

    2016-01-01

    Abstract Alcohol is one of the most common etiologies of liver disease, and alcoholic liver disease overall is the second most common indication for liver transplantation in the United States. It encompasses a spectrum of disease, including fatty liver disease, alcoholic hepatitis (AH), and alcoholic cirrhosis. AH can range from mild to severe disease, with severe disease being defined as: Discriminant Function (DF) ≥ 32, or Model for End-stage Liver Disease (MELD) ≥ 21, or presence of hepatic encephalopathy. Management of the mild disease consists mainly of abstinence and supportive care. Severe AH is associated with significant mortality. Currently, there is no ideal medical treatment for this condition. Besides alcohol cessation, corticosteroids have been used with conflicting results and are associated with an inherent risk of infection. Overall steroids have shown short term benefit when compared to placebo, but they have no obvious long term benefits. Pentoxifylline does not improve survival in patients with severe AH and is no longer recommended based on the results of the STOPAH (Steroid Or Pentoxifylline for Alcoholic Hepatitis) trial. Anti-tumor necrosis factor (TNF) agents are associated with increased risk of life threatening infections and death. Currently, early stage trials are underway, mainly targeting novel pathways based on disease pathogenesis, including modulation of innate immune system, inhibition of gut-liver axis and cell death pathways, and activation of transcription factor farnesyl X receptor (FXR). Future treatment may lie in human induced pluripotent stem cell (iPSC) technology, which is currently under investigation for the study of pathogenesis, drug discovery, and stem cell transplantation. Liver transplantation has been reported with good results in highly selected patients but is controversial due to limited organ supply. PMID:27350941

  12. Alcohol and Hepatitis C

    MedlinePlus

    ... Combat Veterans & their Families Readjustment Counseling (Vet Centers) War Related Illness & Injury Study Center Homeless Veterans Returning ... break of 1 hour between drinks. Drink soda, water, or juice after a drink with alcohol. Do ...

  13. Alcoholic hepatitis 2010: a clinician's guide to diagnosis and therapy.

    PubMed

    Amini, Maziyar; Runyon, Bruce A

    2010-10-21

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

  14. LPS-TLR4 Pathway Mediates Ductular Cell Expansion in Alcoholic Hepatitis

    PubMed Central

    Odena, Gemma; Chen, Jiegen; Lozano, Juan Jose; Altamirano, Jose; Rodrigo-Torres, Daniel; Affo, Silvia; Morales-Ibanez, Oriol; Matsushita, Hiroshi; Zou, Jian; Dumitru, Raluca; Caballeria, Juan; Gines, Pere; Arroyo, Vicente; You, Min; Rautou, Pierre-Emmanuel; Valla, Dominique; Crews, Fulton; Seki, Ekihiro; Sancho-Bru, Pau; Bataller, Ramon

    2016-01-01

    Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease for which there are no effective therapies. Patients with AH show impaired hepatocyte proliferation, expansion of inefficient ductular cells and high lipopolysaccharide (LPS) levels. It is unknown whether LPS mediates ductular cell expansion. We performed transcriptome studies and identified keratin 23 (KRT23) as a new ductular cell marker. KRT23 expression correlated with mortality and LPS serum levels. LPS-TLR4 pathway role in ductular cell expansion was assessed in human and mouse progenitor cells, liver slices and liver injured TLR4 KO mice. In AH patients, ductular cell expansion correlated with portal hypertension and collagen expression. Functional studies in ductular cells showed that KRT23 regulates collagen expression. These results support a role for LPS-TLR4 pathway in promoting ductular reaction in AH. Maneuvers aimed at decreasing LPS serum levels in AH patients could have beneficial effects by preventing ductular reaction development. PMID:27752144

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

    PubMed Central

    Kim, Won; Kim, Dong Joon

    2014-01-01

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

  16. Osteopontin deficiency does not prevent but promotes alcoholic neutrophilic hepatitis in mice

    PubMed Central

    Lazaro, Raul; Wu, Raymond; Lee, Sunyoung; Zhu, Nian-Ling; Chen, Chia-Lin; French, Samuel W.; Xu, Jun; Machida, Keigo; Tsukamoto, Hidekazu

    2014-01-01

    Alcoholic hepatitis (AH) is a distinct spectrum of alcoholic liver disease (ALD) with intense neutrophilic (PMN) inflammation and high mortality. Although a recent study implicates osteopontin (SPP1) in AH, SPP1 is also shown to have protective effects on experimental ALD. To address this unsettled question, we examined the effects of SPP1 deficiency in male mice given 40% calories derived from ad libitum consumption of the Western diet high in cholesterol and saturated fat (HCFD) and the rest from intragastric feeding (iG) of alcohol diet without or with weekly alcohol binge. Weekly binge in this new hybrid feeding model shifts chronic ASH with macrophage inflammation and perisinusoidal and pericelluar fibrosis to AH in 57% (15/26) of the mice, accompanied by inductions of chemokines (Spp1, Cxcl1, Il-17a), progenitor genes (Cd133, Cd24, Nanog, Epcam), PMN infiltration, and clinical features of AH such as hypoalbuminemia, bilirubinemia, and splenomegaly. SPP1 deficiency does not reduce the AH incidence and inductions of progenitor and fibrogenic genes but rather enhances the Il-17a induction and PMN infiltration in some mice. Further, in the absence of SPP1, chronic ASH mice without weekly binge begin to develop AH. In conclusion, these results suggest SPP1 has a protective rather than causal role for experimental AH reproduced in our model. PMID:25132354

  17. Diagnosis and Treatment of Alcoholic Hepatitis: A Systematic Review.

    PubMed

    Singal, Ashwani K; Kodali, Sudha; Vucovich, Lee A; Darley-Usmar, Victor; Schiano, Thomas D

    2016-07-01

    Alcoholic hepatitis (AH) occurs in about one-third of individuals reporting long-term heavy alcohol use. It is associated with high short-term mortality, economic burden, and hospital resources utilization. We performed this systematic review to (i) describe clinical characteristics and genomics associated with the risk of AH; (ii) discuss role and limitations of liver biopsy and prognostic scoring systems; (iii) summarize evidence regarding the currently available therapies including liver transplantation; and (iv) outline emerging therapies with areas of unmet need. Literature search was performed for studies published in English language (January 1971 through March 2016). The following search engines were used: PubMed, Elsevier Embase, PsycINFO, and Cochrane Library. For the treatment section, only randomized controlled studies were included for this review. A total of 138 studies (59 randomized, 22 systematic reviews or meta-analyses, 7 surveys or guidelines, 7 population-based, and 43 prospective cohorts) were cited. There are over 325,000 annual admissions with AH contributing to about 0.8% of all hospitalizations in the United States. Liver biopsy may be required in about 25 to 30% cases for uncertain clinical diagnosis. Corticosteroids with or without N-acetylcysteine remains the only available therapy for severe episodes. Data are emerging on the role of liver transplantation as salvage therapy for select patients. Abstinence remains the most important factor impacting long-term prognosis. Results from the ongoing clinical trials within the National Institute on Alcohol Abuse and Alcoholism-funded consortia are awaited for more effective and safer therapies. AH is a potentially lethal condition with a significant short-term mortality. A high index of suspicion is required. There remains an unmet need for noninvasive biomarkers for the diagnosis, and predicting prognosis and response to therapy. PMID:27254289

  18. Increased activity of the complement system in the liver of patients with alcoholic hepatitis.

    PubMed

    Shen, Hong; French, Barbara A; Liu, Hui; Tillman, Brittany C; French, Samuel W

    2014-12-01

    Inflammation has been suggested as a mechanism underlying the development of alcoholic hepatitis (AH). The activation of the complement system plays an important role in inflammation. Although it has been shown that ethanol-induced activation of the complement system contributes to the pathophysiology of ethanol-induced liver injury in mice, whether ethanol consumption activates the complement system in the human liver has not been investigated. Using antibodies against C1q, C3, and C5, the immunoreactivity of the complement system in patients with AH was examined by immunohistochemistry and quantified by morphometric image analysis. The immunoreactivity intensity of C1q, C3, and C5 in patients with AH was significantly higher than that seen in normal controls. Further, the gene expression of C1q, C3, and C5 was examined using real-time PCR. There were increases in the levels of C1q and C5, but not C3 mRNA in AH. Moreover, the immunoreactivity of C5a receptor (C5aR) also increased in AH. To explore the functional implication of the activation of the complement system in AH, we examined the colocalization of C5aR in Mallory-Denk bodies (MDBs) forming balloon hepatocytes. C5aR was focally overexpressed in the MDB forming cells. Collectively, our study suggests that alcohol consumption increases the activity of the complement system in the liver cells, which contributes to the inflammation-associated pathogenesis of AH.

  19. Advances in alcoholic liver disease: An update on alcoholic hepatitis

    PubMed Central

    Liang, Randy; Liu, Andy; Perumpail, Ryan B; Wong, Robert J; Ahmed, Aijaz

    2015-01-01

    Alcoholic hepatitis is a pro-inflammatory chronic liver disease that is associated with high short-term morbidity and mortality (25%-35% in one month) in the setting of chronic alcohol use. Histopathology is notable for micro- and macrovesicular steatosis, acute inflammation with neutrophil infiltration, hepatocellular necrosis, perivenular and perisinusoidal fibrosis, and Mallory hyaline bodies found in ballooned hepatocytes. Other findings include the characteristic eosinophilic fibrillar material (Mallory’s hyaline bodies) found in ballooned hepatocytes. The presence of focal intense lobular infiltration of neutrophils is what typically distinguishes alcoholic hepatitis from other forms of hepatitis, in which the inflammatory infiltrate is primarily composed of mononuclear cells. Management consists of a multidisciplinary approach including alcohol cessation, fluid and electrolyte correction, treatment of alcohol withdrawal, and pharmacological therapy based on the severity of the disease. Pharmacological treatment for severe alcoholic hepatitis, as defined by Maddrey’s discriminant factor ≥ 32, consists of either prednisolone or pentoxifylline for a period of four weeks. The body of evidence for corticosteroids has been greater than pentoxifylline, although there are higher risks of complications. Recently head-to-head trials between corticosteroids and pentoxifylline have been performed, which again suggests that corticosteroids should strongly be considered over pentoxifylline. PMID:26576078

  20. New treatment options for alcoholic hepatitis

    PubMed Central

    Shasthry, Saggere Muralikrishna; Sarin, Shiv Kumar

    2016-01-01

    The burden of alcoholic liver disease has rapidly grown in the past two decades and is expected to increase further in the coming years. Alcoholic hepatitis, the most florid presentation of alcoholic liver disease, continues to have high morbidity and mortality, with significant financial and healthcare burden with limited treatment options. Steroids remain the current standard of care in severe alcoholic hepatitis in carefully selected patients. No specific treatments are available for those patients who are steroid ineligible, intolerant or unresponsive. Liver transplant has shown good short-term outcome; however, feasibility, ethical and economic concerns remain. Modification of gut microbiota composition and their products, such as lipopolysaccharide, nutritional interventions, immune modulation, increasing steroid sensitivity, genetic polymorphism and epigenetic modification of alcohol induced liver damage, augmenting hepatic regeneration using GCSF are potential therapeutic avenues in steroid non-responsive/ineligible patients. With better understanding of the pathophysiology, using “Omics” platforms, newer options for patients with alcoholic hepatitis are expected soon. PMID:27099434

  1. Recent and currently emerging medical treatment options for the treatment of alcoholic hepatitis

    PubMed Central

    Reep, Gabriel L; Soloway, Roger D

    2011-01-01

    Patients with severe alcoholic hepatitis (AH) need to be treated with specific treatment for better outcome. Currently available specific treatment modalities are use of corticosteroids or pentoxifylline. However, the response rate to these drugs is only about 50%-60%. Hence, there is an urgent need for better and more effective treatment options. Tumor necrosis factor plays an important role in the pathogenesis of AH. However, agents blocking the action of tumor necrosis factor have not been found to be effective. Rather the randomized studies evaluating these agents showed an adverse effect and more infections in treated patients. Critical role of tumor necrosis factor in hepatic regeneration explaining this contrast is discussed. Oxidative stress and inflammation derived from gut bacteria ate two main components in the pathogenesis of AH laying foundation for the role of antioxidants, probiotics, and antibiotics in the management of AH. This article reviews the current data and status of these newer agents for the treatment of AH. Of the various options available, Vitamin E and N-acetylcysteine (NAC) have shown great promise for clinical use as adjunct to corticosteroids. With these encouraging data, future well designed studies are suggested to assess Vitamin E and NAC before their routine use in clinical practice in the management of AH. PMID:21954409

  2. Increased DNA methylation in the livers of patients with alcoholic hepatitis.

    PubMed

    Shen, Hong; French, Barbara A; Tillman, Brittany C; Li, Jun; French, Samuel W

    2015-10-01

    Epigenetic regulation of gene expression has been suggested to play a critical role in the development of alcoholic hepatitis (AH). Although it has been shown that ethanol-induced damage in hepatocytes resulted from a change in methionine metabolism causes global gene expression changes in hepatocytes, the role of the epigenetic machinery in such processes has, however, been barely investigated. 5-Methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are major molecules of epigenetic DNA modification that play an important role in the control of gene expression. Using antibodies against 5mC and 5hmC, the DNA methylation in patients with AH was examined by immunohistochemistry and quantified by morphometric image analysis. The immunoreactivity intensity of 5mC in patients with AH was significantly higher than that seen in normal controls. While there was a trend of decreased 5-hmC in patients with AH, the difference between patients with AH and normal control was not significant. Our study suggests that aberrant DNA-methylation is associated with pathogenesis of AH. PMID:26260903

  3. [Alcohol, steatohepatitis, insulin resistance and hepatitis C].

    PubMed

    Couzigou, P; Mathurin, P; Serfaty, L; Cacoub, P; Moussalli, J; Pialoux, G; Chossegros, P; Cattan, L; Pol, S

    2008-03-01

    Patients with chronic hepatitis C have frequently other morbidities, either because they are frequent in the general population (metabolic syndrome) and/or because the route of contamination (chronic alcohol consumption succeeding to drug abuse). These co-morbidities have a harmfull impact on fibrosis progression during the natural history of HCV infection and reduce the efficacy of antiviral treatments. Thus, it is crucial to diagnose early and treat these different diseases which may be combined. They are the metabolic syndrome and/or chronic alcohol consumption resulting in insuline resistance, infection by the human immune deficiency virus or by the hepatitis B virus as well as chronic tobacco use or excessive consumption of cannabis. An optimal is based on a multidisciplinary approach to reduce fibrosis progression and improve the efficiency of antiviral therapies. However, the hepatologist has to come back to a global care, which is mandatory at the individual level as well as for the public health. PMID:18675184

  4. Immune dysfunction in acute alcoholic hepatitis

    PubMed Central

    Dhanda, Ashwin D; Collins, Peter L

    2015-01-01

    Acute alcoholic hepatitis (AAH) is a serious complication of alcohol misuse and has high short term mortality. It is a clinical syndrome characterised by jaundice and coagulopathy in a patient with a history of recent heavy alcohol use and is associated with profound immune dysfunction with a primed but ineffective immune response against pathogens. Here, we review the current knowledge of the pathogenesis and immune defects of AAH and identify areas requiring further study. Alcohol activates the immune system primarily through the disruption of gut tight junction integrity allowing the escape of pathogen-associated molecular particles (PAMPs) into the portal venous system. PAMPs stimulate cells expressing toll-like receptors (mainly myeloid derived cells) and initiate a network of intercellular signalling by secretion of many soluble mediators including cytokines and chemokines. The latter coordinates the infiltration of neutrophils, monocytes and T cells and results in hepatic stellate cell activation, cellular damage and hepatocyte death by necrosis or apoptosis. On the converse of this immune activation is the growing evidence of impaired microbial defence. Neutrophils have reduced phagocytic capacity and oxidative burst and there is recent evidence that T cell exhaustion plays a role in this. PMID:26576079

  5. Corticosteroids and pentoxifylline for the treatment of alcoholic hepatitis: Current status

    PubMed Central

    Singal, Ashwani K; Walia, Ishmeet; Singal, Anjna; Soloway, Roger D

    2011-01-01

    The treatment of choice for patients with severe alcoholic hepatitis (AH) is use of corticosteroids. Many randomized well designed studies have been reported from all over the world on the use of corticosteroids in the treatment of AH. However, the data on the efficacy of corticosteroids in these patients have been conflicting. Initial meta-analyses also failed to show beneficial effects of corticosteroids. Based on individual data meta-analysis showing clear benefit of corticosteroids amongst patients with severe AH (modified discriminant function of 32 or more), led American College of Gastroenterology to recommend use of corticosteroids as the first line treatment option amongst patients with severe AH. However, corticosteroids are relatively contraindicated amongst patients with severe AH and coexistent sepsis, gastrointestinal bleeding, and acute pancreatitis. These patients may be candidates for second line treatment with pentoxifylline. Further, specific treatment of AH with corticosteroids far from satisfactory with as many as 40%-50% of patients failing to respond to steroids, thus classified as non-responsive to steroids. The management of these patients is a continuing challenge for physicians. Better treatment modalities need to be developed for this group of patients in order to improve the outcome of patients with severe AH. This article describes at length the available trials on use of corticosteroids and pentoxifylline with their current status. Route of administration, dosage, adverse effects, and mechanisms of action of these two drugs are also discussed. Finally, an algorithm with clinical approach to management of patients who present with clinical syndrome of AH is described. PMID:21954408

  6. Kinase analysis in alcoholic hepatitis identifies p90RSK as a potential mediator of liver fibrogenesis

    PubMed Central

    Morales-Ibanez, Oriol; Affò, Silvia; Rodrigo-Torres, Daniel; Blaya, Delia; Millán, Cristina; Coll, Mar; Perea, Luis; Odena, Gemma; Knorpp, Thomas; Templin, Markus F; Moreno, Montserrat; Altamirano, José; Miquel, Rosa; Arroyo, Vicente; Ginès, Pere; Caballería, Juan; Sancho-Bru, Pau; Bataller, Ramon

    2015-01-01

    Objective Alcoholic hepatitis (AH) is often associated with advanced fibrosis, which negatively impacts survival. We aimed at identifying kinases deregulated in livers from patients with AH and advanced fibrosis in order to discover novel molecular targets. Design Extensive phosphoprotein analysis by reverse phase protein microarrays was performed in AH (n=12) and normal human livers (n=7). Ribosomal S6 kinase (p90RSK) hepatic expression was assessed by qPCR, Western blot and immunohistochemistry. Kaempferol was used as a selective pharmacological inhibitor of the p90RSK pathway to assess the regulation of experimentally-induced liver fibrosis and injury, using in vivo and in vitro approaches. Results Proteomic analysis identified p90RSK as one of the most deregulated kinases in AH. Hepatic p90RSK gene and protein expression was also upregulated in livers with chronic liver disease. Immunohistochemistry studies showed increased p90RSK staining in areas of active fibrogenesis in cirrhotic livers. Therapeutic administration of kaempferol to carbon tetrachloride-treated mice resulted in decreased hepatic collagen deposition, and expression of profibrogenic and proinflammatory genes, compared to vehicle administration. In addition, kaempferol reduced the extent of hepatocellular injury and degree of apoptosis. In primary hepatic stellate cells, kaempferol and small interfering RNA decreased activation of p90RSK, which in turn regulated key profibrogenic actions. In primary hepatocytes, kaempferol attenuated proapoptotic signalling. Conclusions p90RSK is upregulated in patients with chronic liver disease and mediates liver fibrogenesis in vivo and in vitro. These results suggest that the p90RSK pathway could be a new therapeutic approach for liver diseases characterised by advanced fibrosis. PMID:25652085

  7. Alcoholic Hepatitis Markedly Decreases the Capacity for Urea Synthesis

    PubMed Central

    Glavind, Emilie; Aagaard, Niels Kristian; Grønbæk, Henning; Møller, Holger Jon; Orntoft, Nikolaj Worm; Vilstrup, Hendrik; Thomsen, Karen Louise

    2016-01-01

    Background and Aim Data on quantitative metabolic liver functions in the life-threatening disease alcoholic hepatitis are scarce. Urea synthesis is an essential metabolic liver function that plays a key regulatory role in nitrogen homeostasis. The urea synthesis capacity decreases in patients with compromised liver function, whereas it increases in patients with inflammation. Alcoholic hepatitis involves both mechanisms, but how these opposite effects are balanced remains unclear. Our aim was to investigate how alcoholic hepatitis affects the capacity for urea synthesis. We related these findings to another measure of metabolic liver function, the galactose elimination capacity (GEC), as well as to clinical disease severity. Methods We included 20 patients with alcoholic hepatitis and 7 healthy controls. The urea synthesis capacity was quantified by the functional hepatic nitrogen clearance (FHNC), i.e., the slope of the linear relationship between the blood α-amino nitrogen concentration and urea nitrogen synthesis rate during alanine infusion. The GEC was determined using blood concentration decay curves after intravenous bolus injection of galactose. Clinical disease severity was assessed by the Glasgow Alcoholic Hepatitis Score and Model for End-Stage Liver Disease (MELD) score. Results The FHNC was markedly decreased in the alcoholic hepatitis patients compared with the healthy controls (7.2±4.9 L/h vs. 37.4±6.8 L/h, P<0.01), and the largest decrease was observed in those with severe alcoholic hepatitis (4.9±3.6 L/h vs. 9.9±4.9 L/h, P<0.05). The GEC was less markedly reduced than the FHNC. A negative correlation was detected between the FHNC and MELD score (rho = -0.49, P<0.05). Conclusions Alcoholic hepatitis markedly decreases the urea synthesis capacity. This decrease is associated with an increase in clinical disease severity. Thus, the metabolic failure in alcoholic hepatitis prevails such that the liver cannot adequately perform the metabolic up

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

    PubMed Central

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

    2015-01-01

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

  9. A neurotoxic alcohol exposure paradigm does not induce hepatic encephalopathy.

    PubMed

    Hashimoto, Joel G; Wiren, Kristine M; Wilhelm, Clare J

    2016-01-01

    Alcohol abuse is associated with neurological dysfunction, brain morphological deficits and frank neurotoxicity. Although these disruptions may be a secondary effect due to hepatic encephalopathy, no clear evidence of causality is available. This study examined whether a 72h period of alcohol intoxication known to induce physical dependence, followed by a single withdrawal, was sufficient to induce signs of hepatic encephalopathy in male and female mice. Animals were continuously intoxicated via alcohol vapor inhalation, a procedure previously shown to induce significant neurotoxicity in female mice. At peak synchronized withdrawal (8h following the end of alcohol exposure), blood samples were taken and levels of several liver-regulated markers and brain swelling were characterized. Glutathione levels were also determined in the medial frontal cortex (mFC) and hippocampus. Results revealed elevated levels of cholesterol, albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT) and decreased levels of blood urea nitrogen and total bilirubin in alcohol-exposed male and female groups compared to controls. Brain water weight was not affected by alcohol exposure, though males tended to have slightly more water weight overall. Alcohol exposure led to reductions in tissue levels of glutathione in both the hippocampus and mFC which may indicate increased oxidative stress. Combined, these results suggest that hepatic encephalopathy does not appear to play a significant role in the neurotoxicity observed following alcohol exposure in this model. PMID:27268733

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

    PubMed

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

    2014-10-01

    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-1β 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-1β, IL-18, and other inflammatory components including IL-6, IL-10, TNF-α, IFN-γ, 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-α 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

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

    PubMed

    Zakhari, Samir

    2013-08-01

    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

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

    PubMed

    Zakhari, Samir

    2013-08-01

    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.

  13. Hepatic alcohol dehydrogenase activity in alcoholic subjects with and without liver disease.

    PubMed Central

    Vidal, F; Perez, J; Morancho, J; Pinto, B; Richart, C

    1990-01-01

    Alcohol dehydrogenase activity was measured in samples of liver tissue from a group of alcoholic and non-alcoholic subjects to determine whether decreased liver alcohol dehydrogenase activity is a consequence of ethanol consumption or liver damage. The alcoholic patients were classified further into the following groups: control subjects with no liver disease (group 1), subjects with non-cirrhotic liver disease (group 2), and subjects with cirrhotic liver disease (group 3). The non-alcoholic subjects were also divided, using the same criteria, into groups 4, 5, and 6, respectively. The analysis of the results showed no significant differences when mean alcohol dehydrogenase activities of alcoholic and non-alcoholic patients with similar degrees of liver pathology were compared (groups 1 v 4, 2 v 5, and 3 v 6. Alcohol dehydrogenase activity was, however, severely reduced in patients with liver disease compared with control subjects. Our findings suggest that alcohol consumption does not modify hepatic alcohol dehydrogenase activity. The reduction in specific alcohol dehydrogenase activity in alcoholic liver disease is a consequence of liver damage. PMID:2379876

  14. Severe alcoholic hepatitis: Glucocorticoid saves lives and transplantation is promising

    PubMed Central

    Braillon, Alain

    2011-01-01

    Glucocorticosteroids have been used as the only treatment for a long time which significantly reduced the mortality of the patients with severe alcoholic hepatitis. The efficacy of transplantation has been recently addressed in a pilot study. The result seems promising but needs larger multicenter trials. PMID:21633648

  15. Failure of carnitine in improving hepatic nitrogen content in alcoholic and non‐alcoholic malnourished rats

    PubMed Central

    Rodrigues, Luciana P; Portari, Guilherme Vannucchi; Padovan, Gilberto João; Jordão, Alceu Afonso; Suen, Vivian M M; Sergio Marchini, Julio

    2010-01-01

    AIMS: To investigate the effect of carnitine supplementation on alcoholic malnourished rats' hepatic nitrogen content. METHODS: Malnourished rats, on 50% protein‐calorie restriction with free access to water (malnutrition group) and malnourished rats under the same conditions with free access to a 20% alcohol/water solution (alcohol group) were studied. After the undernourishment period (4 weeks with or without alcohol), both groups were randomly divided into two subgroups, one of them nutritionally recovered for 28 days with free access to a normal diet and water (recovery groups) and the other re‐fed with free access to diet and water plus carnitine (0.1 g/g body weight/day by gavage) (carnitine groups). No alcohol intake was allowed during the recovery period. RESULTS: The results showed: i) no difference between the alcohol/no alcohol groups, with or without carnitine, regarding body weight gain, diet consumption, urinary nitrogen excretion, plasma free fatty acids, lysine, methionine, and glycine. ii) Liver nitrogen content was highest in the carnitine recovery non‐alcoholic group (from 1.7 to 3.3 g/100 g, P<0.05) and lowest in alcoholic animals (about 1.5 g/100g). iii) Hepatic fat content (∼10 g/100 g, P>.05) was highest in the alcoholic animals. CONCLUSION: Carnitine supplementation did not induce better nutritional recovery. PMID:21049216

  16. Hepatic folate metabolism in the chronic alcoholic monkey

    SciTech Connect

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

    1981-05-01

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

  17. Establishment of a hepatic cirrhosis and portal hypertension model by hepatic arterial perfusion with 80% alcohol

    PubMed Central

    Wang, Lei; He, Fu-Liang; Liu, Fu-Quan; Yue, Zhen-Dong; Zhao, Hong-Wei

    2015-01-01

    AIM: To determine the feasibility and safety of establishing a porcine hepatic cirrhosis and portal hypertension model by hepatic arterial perfusion with 80% alcohol. METHODS: Twenty-one healthy Guizhou miniature pigs were randomly divided into three experimental groups and three control groups. The pigs in the three experimental groups were subjected to hepatic arterial perfusion with 7, 12 and 17 mL of 80% alcohol, respectively, while those in the three control groups underwent hepatic arterial perfusion with 7, 12 and 17 mL of saline, respectively. Hepatic arteriography and direct portal phlebography were performed on all animals before and after perfusion, and the portal venous pressure and diameter were measured before perfusion, immediately after perfusion, and at 2, 4 and 6 wk after perfusion. The following procedures were performed at different time points: routine blood sampling, blood biochemistry, blood coagulation and blood ammonia tests before surgery, and at 2, 4 and 6 wk after surgery; hepatic biopsy before surgery, within 6 h after surgery, and at 1, 2, 3, 4 and 5 wk after surgery; abdominal enhanced computed tomography examination before surgery and at 6 wk after surgery; autopsy and multi-point sampling of various liver lobes for histological examination at 6 wk after surgery. RESULTS: In experimental group 1, different degrees of hepatic fibrosis were observed, and one pig developed hepatic cirrhosis. In experimental group 2, there were cases of hepatic cirrhosis, different degrees of increased portal venous pressure, and intrahepatic portal venous bypass, but neither extrahepatic portal-systemic bypass circulation nor death occurred. In experimental group 3, two animals died and three animals developed hepatic cirrhosis, and different degrees of increased portal venous pressure and intrahepatic portal venous bypass were also observed, but there was no extrahepatic portal-systemic bypass circulation. CONCLUSION: It is feasible to establish an

  18. Alcoholic liver disease and hepatitis C virus infection

    PubMed Central

    Novo-Veleiro, Ignacio; Alvela-Suárez, Lucía; Chamorro, Antonio-Javier; González-Sarmiento, Rogelio; Laso, Francisco-Javier; Marcos, Miguel

    2016-01-01

    Alcohol consumption and hepatitis C virus (HCV) infection have a synergic hepatotoxic effect, and the coexistence of these factors increases the risk of advanced liver disease. The main mechanisms of this effect are increased viral replication and altered immune response, although genetic predisposition may also play an important role. Traditionally, HCV prevalence has been considered to be higher (up to 50%) in alcoholic patients than in the general population. However, the presence of advanced alcoholic liver disease (ALD) or intravenous drug use (IDU) may have confounded the results of previous studies, and the real prevalence of HCV infection in alcoholic patients without ALD or prior IDU has been shown to be lower. Due to the toxic combined effect of HCV and alcohol, patients with HCV infection should be screened for excessive ethanol intake. Patients starting treatment for HCV infection should be specifically advised to stop or reduce alcohol consumption because of its potential impact on treatment efficacy and adherence and may benefit from additional support during antiviral therapy. This recommendation might be extended to all currently recommended drugs for HCV treatment. Patients with alcohol dependence and HCV infection, can be treated with acamprosate, nalmefene, topiramate, and disulfiram, although baclofen is the only drug specifically tested for this purpose in patients with ALD and/or HCV infection. PMID:26819510

  19. Interaction between the NS4B amphipathic helix, AH2, and charged lipid headgroups alters membrane morphology and AH2 oligomeric state — Implications for the Hepatitis C virus life cycle

    PubMed Central

    Ashworth Briggs, Esther L.; Gomes, Rafael G.B.; Elhussein, Malaz; Collier, William; Stuart Findlow, I.; Khalid, Syma; McCormick, Chris J.; Williamson, Philip T.F.

    2015-01-01

    The non-structural protein 4B (NS4B) from Hepatitis C virus (HCV) plays a pivotal role in the remodelling of the host cell's membranes, required for the formation of the viral replication complex where genome synthesis occurs. NS4B is an integral membrane protein that possesses a number of domains vital for viral replication. Structural and biophysical studies have revealed that one of these, the second amphipathic N-terminal helix (AH2), plays a key role in these remodelling events. However, there is still limited understanding of the mechanism through which AH2 promotes these changes. Here we report on solid-state NMR and molecular dynamics studies that demonstrate that AH2 promotes the clustering of negatively charged lipids within the bilayer, a process that reduces the strain within the bilayer facilitating the remodelling of the lipid bilayer. Furthermore, the presence of negatively charged lipids within the bilayer appears to promote the disassociation of AH2 oligomers, highlighting a potential role for lipid recruitment in regulating NS protein interactions. PMID:25944559

  20. Alcohol produces distinct hepatic lipidome and eicosanoid signature in lean and obese.

    PubMed

    Puri, Puneet; Xu, Jun; Vihervaara, Terhi; Katainen, Riikka; Ekroos, Kim; Daita, Kalyani; Min, Hae-Ki; Joyce, Andrew; Mirshahi, Faridoddin; Tsukamoto, Hidekazu; Sanyal, Arun J

    2016-06-01

    Alcohol- and obesity-related liver diseases often coexist. The hepatic lipidomics due to alcohol and obesity interaction is unknown. We characterized the hepatic lipidome due to 1) alcohol consumption in lean and obese mice and 2) obesity and alcohol interactions. In the French-Tsukamoto mouse model, intragastric alcohol or isocaloric dextrose were fed with either chow (lean) or high-fat, high-cholesterol diet (obese). Four groups (lean, lean alcohol, obese, and obese alcohol) were studied. MS was performed for hepatic lipidomics, and data were analyzed. Alcohol significantly increased hepatic cholesteryl esters and diacyl-glycerol in lean and obese but was more pronounced in obese. Alcohol produced contrasting changes in hepatic phospholipids with significant enrichment in lean mice versus significant decrease in obese mice, except phosphatidylglycerol, which was increased in both lean and obese alcohol groups. Most lysophospholipids were increased in lean alcohol and obese mice without alcohol use only. Prostaglandin E2; 5-, 8-, and 11-hydroxyeicosatetraenoic acids; and 9- and 13-hydroxyoctadecadienoic acids were considerably increased in obese mice with alcohol use. Alcohol consumption produced distinct changes in lean and obese with profound effects of obesity and alcohol interaction on proinflammatory and oxidative stress-related eicosanoids.

  1. Role of osteopontin in hepatic neutrophil infiltration during alcoholic steatohepatitis

    SciTech Connect

    Apte, Udayan M.; Banerjee, Atrayee; McRee, Rachel; Wellberg, Elizabeth; Ramaiah, Shashi K. . E-mail: sramaiah@cvm.tamu.edu

    2005-08-22

    Alcoholic liver disease (ALD) is a major complication of heavy alcohol (EtOH) drinking and is characterized by three progressive stages of pathology: steatosis, steatohepatitis, and fibrosis/cirrhosis. Alcoholic steatosis (AS) is the initial stage of ALD and consists of fat accumulation in the liver accompanied by minimal liver injury. AS is known to render the hepatocytes increasingly sensitive to toxicants such as bacterial endotoxin (LPS). Alcoholic steatohepatitis (ASH), the second and rate-limiting step in the progression of ALD, is characterized by hepatic fat accumulation, neutrophil infiltration, and neutrophil-mediated parenchymal injury. However, the pathogenesis of ASH is poorly defined. It has been theorized that the pathogenesis of ASH involves interaction of increased circulating levels of LPS with hepatocytes being rendered highly sensitive to LPS due to heavy EtOH consumption. We hypothesize that osteopontin (OPN), a matricellular protein (MCP), plays an important role in the hepatic neutrophil recruitment due to its enhanced expression during the early phase of ALD (AS and ASH). To study the role of OPN in the pathogenesis of ASH, we induced AS in male Sprague-Dawley rats by feeding EtOH-containing Lieber-DeCarli liquid diet for 6 weeks. AS rats experienced extensive fat accumulation and minimal liver injury. Moderate induction in OPN was observed in AS group. ASH was induced by feeding male Sprague-Dawley rats EtOH-containing Lieber-DeCarli liquid diet for 6 weeks followed by LPS injection. The ASH rats had substantial neutrophil infiltration, coagulative oncotic necrosis, and developed higher liver injury. Significant increases in the hepatic and circulating levels of OPN was observed in the ASH rats. Higher levels of the active, thrombin-cleaved form of OPN in the liver in ASH group correlated remarkably with hepatic neutrophil infiltration. Finally, correlative studies between OPN and hepatic neutrophil infiltration was corroborated in a simple

  2. The Altered Hepatic Tubulin Code in Alcoholic Liver Disease

    PubMed Central

    Groebner, Jennifer L.; Tuma, Pamela L.

    2015-01-01

    The molecular mechanisms that lead to the progression of alcoholic liver disease have been actively examined for decades. Because the hepatic microtubule cytoskeleton supports innumerable cellular processes, it has been the focus of many such mechanistic studies. It has long been appreciated that α-tubulin is a major target for modification by highly reactive ethanol metabolites and reactive oxygen species. It is also now apparent that alcohol exposure induces post-translational modifications that are part of the natural repertoire, mainly acetylation. In this review, the modifications of the “tubulin code” are described as well as those adducts by ethanol metabolites. The potential cellular consequences of microtubule modification are described with a focus on alcohol-induced defects in protein trafficking and enhanced steatosis. Possible mechanisms that can explain hepatic dysfunction are described and how this relates to the onset of liver injury is discussed. Finally, we propose that agents that alter the cellular acetylation state may represent a novel therapeutic strategy for treating liver disease. PMID:26393662

  3. Experimental alcohol-induced hepatic necrosis: suppression by propylthiouracil.

    PubMed

    Israel, Y; Kalant, H; Orrego, H; Khanna, J M; Videla, L; Phillips, J M

    1975-03-01

    We have previously reported that a hypermetabolic state, resembling that produced by thryoid hormones, exists in the livers of animals treated chronically with ethanol. We propose that this alteration produces a relative hypoxia in the centrilobular zone of the liver which, if severe enough, leads to cellular death and to the production of hepatitis. Rats consuming ethanol for 30 days, given with a nutritionally adequate diet, and exposed to reduced oxygen tensions for only 6 hr, developed histological and biochemical evidence of hepatocellular necrosis and inflammatory lesions confined to the centrilobular zone. The severity was proportional to the degree of hypoxia. Pair-fed (nonalcohol) controls showed no such lesions. Treatment of the animals with propylthiouracil for 3-10 days abolished the hypermetabolic state of the liver in ethanol-consuming animals, and drastically reduced the histological and biochemical effects of hypoxia in them. These findings may have implications for pathogenesis and treatment of alcoholic hepatitis in man.

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

    PubMed

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

    2014-01-01

    Hepatitis C virus (HCV) has become a major public health issue. It is prevalent in most countries. HCV infection frequently begins without clinical symptoms, before progressing to persistent viremia, chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) in the majority of patients (70% to 80%). Alcohol is an independent cofactor that accelerates the development of HCC in chronic hepatitis C patients. The purpose of the current study was to evaluate ethanol-induced hepatic changes in HCV core-Tg mice and mutant core Tg mice. Wild type (NTG), core wild-Tg mice (TG-K), mutant core 116-Tg mice (TG-116) and mutant core 99-Tg mice (TG-99) were used in this investigation. All groups were given drinking water with 10% ethanol and 5% sucrose for 13 weeks. To observe liver morphological changes, we performed histopathological and immunohistochemical examinations. Histopathologically, NTG, TG-K and TG-116 mice showed moderate centrilobular necrosis, while severe centrilobular necrosis and hepatocyte dissociation were observed in TG-99 mice with increasing lymphocyte infiltration and piecemeal necrosis. In all groups, a small amount of collagen fiber was found, principally in portal areas. None of the mice were found to have myofibroblasts based on immunohistochemical staining specific for α-SMA. CYP2E1-positive cells were clearly detected in the centrilobular area in all groups. In the TG-99 mice, we also observed cells positive for CK8/18, TGF-β1 and phosphorylated (p)-Smad2/3 and p21 around the necrotic hepatocytes in the centrilobular area (p < 0.01). Based on our data, alcohol intake induced piecemeal necrosis and hepatocyte dissociation in the TG-99 mice. These phenomena involved activation of the TGF-β1/p-Smad2/3/p21 signaling pathway in hepatocytes. Data from this study will be useful for elucidating the association between alcohol intake and HCV infection.

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

    PubMed

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

    2014-09-14

    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

  6. Chronic alcohol consumption has a biphasic effect on hepatic retinoid loss

    PubMed Central

    Clugston, Robin D.; Huang, Li-Shin; Blaner, William S.

    2015-01-01

    The alcohol-induced depletion of hepatic retinoid stores correlates with the progression of liver injury; however, the mechanisms underlying alcohol’s effects have not been fully elucidated. Our goal was to gain a mechanistic understanding of alcohol-induced hepatic retinoid depletion. Wild-type and mutant mice were continuously fed alcohol through Lieber-DeCarli liquid diets, with matched control animals pair fed an isocaloric alcohol-free diet to ensure equal nutrient and calorie intake between groups. A systematic analysis of tissue retinol and retinyl ester levels was performed with HPLC, complemented by gene and protein expression analyses. Our results delineated 2 phases of alcohol-induced depletion of hepatic retinoid. Initially, ∼15% of hepatic retinoid content was mobilized from the liver, causing extrahepatic tissue retinoid levels to increase. Subsequently, there was a precipitous drop in hepatic retinoid content (>60%), without further retinoid accumulation in the periphery. Follow-up studies in mutant mice revealed roles for RBP, CRBP1, and CD36 in retinoid mobilization and extrahepatic retinoid uptake, as well as a role for CYP2E1 in the catabolism of hepatic retinoid. In summary, alcohol has a biphasic effect on hepatic retinoid stores, characterized by an initial phase of rapid mobilization to extrahepatic tissues followed by extensive catabolism within the liver.—Clugston, R. D., Huang, L.-S., Blaner, W. S. Chronic alcohol consumption has a biphasic effect on hepatic retinoid loss. PMID:25985802

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

    PubMed

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

    2014-10-28

    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.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-10-28

    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

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

    PubMed

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

    2013-07-01

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

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

    PubMed

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

    2012-07-01

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

  12. Fibroblast growth factor 21 deficiency exacerbates chronic alcohol-induced hepatic steatosis and injury

    PubMed Central

    Liu, Yanlong; Zhao, Cuiqing; Xiao, Jian; Liu, Liming; Zhang, Min; Wang, Cuiling; Wu, Guicheng; Zheng, Ming-Hua; Xu, Lan-Man; Chen, Yong-Ping; Mohammadi, Moosa; Chen, Shao-Yu; Cave, Matthew; McClain, Craig; Li, Xiaokun; Feng, Wenke

    2016-01-01

    Fibroblast growth factor 21 (FGF21) is a hepatokine that regulates glucose and lipid metabolism in the liver. We sought to determine the role of FGF21 in hepatic steatosis in mice exposed to chronic alcohol treatment and to discern underlying mechanisms. Male FGF21 knockout (FGF21 KO) and control (WT) mice were divided into groups that were fed either the Lieber DeCarli diet containing 5% alcohol or an isocaloric (control) diet for 4 weeks. One group of WT mice exposed to alcohol received recombinant human FGF21 (rhFGF21) in the last 5 days. Liver steatosis and inflammation were assessed. Primary mouse hepatocytes and AML-12 cells were incubated with metformin or rhFGF21. Hepatic genes and the products involved in in situ lipogenesis and fatty acid β-oxidation were analyzed. Alcohol exposure increased circulating levels and hepatic expression of FGF21. FGF21 depletion exacerbated alcohol-induced hepatic steatosis and liver injury, which was associated with increased activation of genes involved in lipogenesis mediated by SREBP1c and decreased expression of genes involved in fatty acid β-oxidation mediated by PGC1α. rhFGF21 administration reduced alcohol-induced hepatic steatosis and inflammation in WT mice. These results reveal that alcohol-induced FGF21 expression is a hepatic adaptive response to lipid dysregulation. Targeting FGF21 signaling could be a novel treatment approach for alcoholic steatohepatitis. PMID:27498701

  13. Fibroblast growth factor 21 deficiency exacerbates chronic alcohol-induced hepatic steatosis and injury.

    PubMed

    Liu, Yanlong; Zhao, Cuiqing; Xiao, Jian; Liu, Liming; Zhang, Min; Wang, Cuiling; Wu, Guicheng; Zheng, Ming-Hua; Xu, Lan-Man; Chen, Yong-Ping; Mohammadi, Moosa; Chen, Shao-Yu; Cave, Matthew; McClain, Craig; Li, Xiaokun; Feng, Wenke

    2016-01-01

    Fibroblast growth factor 21 (FGF21) is a hepatokine that regulates glucose and lipid metabolism in the liver. We sought to determine the role of FGF21 in hepatic steatosis in mice exposed to chronic alcohol treatment and to discern underlying mechanisms. Male FGF21 knockout (FGF21 KO) and control (WT) mice were divided into groups that were fed either the Lieber DeCarli diet containing 5% alcohol or an isocaloric (control) diet for 4 weeks. One group of WT mice exposed to alcohol received recombinant human FGF21 (rhFGF21) in the last 5 days. Liver steatosis and inflammation were assessed. Primary mouse hepatocytes and AML-12 cells were incubated with metformin or rhFGF21. Hepatic genes and the products involved in in situ lipogenesis and fatty acid β-oxidation were analyzed. Alcohol exposure increased circulating levels and hepatic expression of FGF21. FGF21 depletion exacerbated alcohol-induced hepatic steatosis and liver injury, which was associated with increased activation of genes involved in lipogenesis mediated by SREBP1c and decreased expression of genes involved in fatty acid β-oxidation mediated by PGC1α. rhFGF21 administration reduced alcohol-induced hepatic steatosis and inflammation in WT mice. These results reveal that alcohol-induced FGF21 expression is a hepatic adaptive response to lipid dysregulation. Targeting FGF21 signaling could be a novel treatment approach for alcoholic steatohepatitis. PMID:27498701

  14. Pathogenesis of alcoholic hepatitis: Role of inflammatory signaling and oxidative stress

    PubMed Central

    Jampana, Sarat C; Khan, Rashid

    2011-01-01

    Inflammatory signaling and oxidative stress are two major components in the pathogenesis of alcoholic hepatitis. Alcohol consumption results in translocation of gut bacteria into the portal system along with lipopolysaccharides that interact with toll-like receptors and results in the production of inflammatory and immunogenic mediators such as tumor necrosis factor-alpha (TNF-α) and interferons. Chronic consumption of alcohol causes priming of this process in which there is enhanced production of cytokines, interferon, interleukins, and TNF-α. Oxidative stress, genetic predisposition, and the unfolded protein response are other contributory mechanisms. Novel therapies aimed at these pathways may prevent, decrease, or delay the complications of alcoholic hepatitis. PMID:21731903

  15. Hepatotherapeutic effect of Aloe vera in alcohol-induced hepatic damage.

    PubMed

    Saka, W A; Akhigbe, R E; Ishola, O S; Ashamu, E A; Olayemi, O T; Adeleke, G E

    2011-07-15

    There is a lack of reliable hepatotherapeutic drugs in modern medicine in the management of alcohol/drug-induced liver damage. Aloe vera extract has been used in folklore medicine for its medicinal values. This study evaluates the hepatotherapeutic activity of aqueous extract of Aloe vera gel in rats. Sprague-Dawley rats were divided into three groups; the negative control, positive control and the extract-treated groups. The negative control received only distilled water daily. The positive control received alcohol, while the extract-treated group received aqueous extract of Aloe vera and alcohol. Hepatotoxicity was induced in the positive control and extract-treated rats with alcohol. The hepatotherapeutic effect was evaluated by performing an assay of the serum total bilirubin, alkaline phosphatase, aspartate and alanine transaminases and liver histopathology. Alanine transaminase activities were comparable in all groups. Alcohol treatment alone significantly (p < 0.05) increased total serum bilirubin, alkaline phosphatase and aspartate transaminase activities. Alcohol-induced hepatic dysfunction was abrogated by Aloe vera extract. Histopathological examination revealed that alcohol induced hepatic damage. Aloe vera treatment maintained hepatic architecture similar to that seen in the control. This study shows that aqueous extract of Aloe vera gel is hepatotherapeutic and thus lends credence to the use of the plant in folklore medicine in the management of alcohol-induced hepatic dysfunction.

  16. Hepatic microsomal cytochrome p450s and chlorinated hydrocarbons in largha and ribbon seals from Hokkaido, Japan: differential response of seal species to Ah receptor agonist exposure.

    PubMed

    Chiba, Issei; Sakakibara, Akihito; Iwata, T Hisato; Ishizuka, Mayumi; Tanabe, Shinsuke; Akahori, Fumiaki; Kazusaka, Akio; Fujita, Shoichi

    2002-04-01

    From 16 largha seals (Phoca largha) and 15 ribbon seals (Phoca fasciata) in the coastal waters of Hokkaido, Japan, blubber chlorinated hydrocarbon (CHC) levels and hepatic cytochrome P450 (CYP) catalytic activities and their immunochemically detected protein content levels were measured. Concentrations of DDTs (2,2-bis(4-chlorophenyl)-1,1-dichloroethylene,p,p'-DDE; 2,2-bis(4-chlorophenyl)-1,1-dichloroethane, p,p'-DDD; dichlorodiphenyltrichloroethane, p,p'-DDT), polychlorinated biphenyl congeners (PCBs), and chlordane compounds (oxychlordane, chlordanes, and nonachlors) in both species were in the range of 290 to 5,300, 420 to 4,000, and 130 to 1,500 ng/g lipid weight, respectively. Aryl hydrocarbon receptor (AhR) agonists, non-ortho (IUPAC 77 and 126) and mono-ortho (IUPAC 105, 118, and 156) coplanar PCB congeners, were also detected, and the 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) toxic equivalents (TEQs) were 4.9 to 120 pg TEQ/g lipid weight. Cross-reactive proteins with polyclonal antibodies against rat CYP1A1 and CYP3A2 were notably detected in seal liver microsomes. Interestingly, a polyclonal antibody against rat CYP2B1 recognized proteins only at trace levels. In largha seals, both levels of alkoxyresorufin- (methoxy-, ethoxy-, pentoxy-, and benzyloxyresorufin) O-dealkylase (AROD) activities and proteins detected by polyclonal antibodies against rat CYP1A1 were significantly correlated with the concentrations of individual coplanar PCB congeners, total TEQs, and total PCBs. Threshold concentrations for TEQs in blubber of the largha seal to induce hepatic CYP1A protein and EROD activity were estimated to be 8.5 and 19 pg TEQ/g fat weight, respectively. In ribbon seals, similar correlations were not detected, although the TEQ levels were not significantly lower than those in largha seals. These results suggest that AROD activity and CYP1A1 protein in the liver of the largha seal could be a biomarker for the exposure to AhR agonists such as coplanar PCB

  17. Alcohol Increases Liver Progenitor Populations and Induces Disease Phenotypes in Human IPSC-Derived Mature Stage Hepatic Cells.

    PubMed

    Tian, Lipeng; Deshmukh, Abhijeet; Prasad, Neha; Jang, Yoon-Young

    2016-01-01

    Alcohol consumption has long been a global problem affecting human health, and has been found to influence both fetal and adult liver functions. However, how alcohol affects human liver development and liver progenitor cells remains largely unknown. Here, we used human induced pluripotent stem cells (iPSCs) as a model to examine the effects of alcohol, on multi-stage hepatic cells including hepatic progenitors, early and mature hepatocyte-like cells derived from human iPSCs. While alcohol has little effect on endoderm development from iPSCs, it reduces formation of hepatic progenitor cells during early hepatic specification. The proliferative activities of early and mature hepatocyte-like cells are significantly decreased after alcohol exposure. Importantly, at a mature stage of hepatocyte-like cells, alcohol treatment increases two liver progenitor subsets, causes oxidative mitochondrial injury and results in liver disease phenotypes (i.e., steatosis and hepatocellular carcinoma associated markers) in a dose dependent manner. Some of the phenotypes were significantly improved by antioxidant treatment. This report suggests that fetal alcohol exposure may impair generation of hepatic progenitors at early stage of hepatic specification and decrease proliferation of fetal hepatocytes; meanwhile alcohol injury in post-natal or mature stage human liver may contribute to disease phenotypes. This human iPSC model of alcohol-induced liver injury can be highly valuable for investigating alcoholic injury in the fetus as well as understanding the pathogenesis and ultimately developing effective treatment for alcoholic liver disease in adults. PMID:27570479

  18. Alcohol Increases Liver Progenitor Populations and Induces Disease Phenotypes in Human IPSC-Derived Mature Stage Hepatic Cells

    PubMed Central

    Tian, Lipeng; Deshmukh, Abhijeet; Prasad, Neha; Jang, Yoon-Young

    2016-01-01

    Alcohol consumption has long been a global problem affecting human health, and has been found to influence both fetal and adult liver functions. However, how alcohol affects human liver development and liver progenitor cells remains largely unknown. Here, we used human induced pluripotent stem cells (iPSCs) as a model to examine the effects of alcohol, on multi-stage hepatic cells including hepatic progenitors, early and mature hepatocyte-like cells derived from human iPSCs. While alcohol has little effect on endoderm development from iPSCs, it reduces formation of hepatic progenitor cells during early hepatic specification. The proliferative activities of early and mature hepatocyte-like cells are significantly decreased after alcohol exposure. Importantly, at a mature stage of hepatocyte-like cells, alcohol treatment increases two liver progenitor subsets, causes oxidative mitochondrial injury and results in liver disease phenotypes (i.e., steatosis and hepatocellular carcinoma associated markers) in a dose dependent manner. Some of the phenotypes were significantly improved by antioxidant treatment. This report suggests that fetal alcohol exposure may impair generation of hepatic progenitors at early stage of hepatic specification and decrease proliferation of fetal hepatocytes; meanwhile alcohol injury in post-natal or mature stage human liver may contribute to disease phenotypes. This human iPSC model of alcohol-induced liver injury can be highly valuable for investigating alcoholic injury in the fetus as well as understanding the pathogenesis and ultimately developing effective treatment for alcoholic liver disease in adults. PMID:27570479

  19. Alcohol consumption among patients with hepatitis B infection in northern Portugal considering gender and hepatitis B virus genotype differences.

    PubMed

    Mota, Ana; Guedes, Fátima; Areias, Jorge; Pinho, Luciana; Cardoso, Margarida Fonseca

    2010-03-01

    Alcohol abuse is an important public health problem. In Portugal with a population of 10 millions of inhabitants, there are around 10% of alcoholics or excessive alcohol drinkers and 1% of chronically infected patients with hepatitis B virus (HBV). To examine the characteristics of patients with higher levels of alcohol consumption and to investigate the association between alcohol consumption and liver damage a total of 298 chronically infected individuals, with HBV genotyped and submitted to liver biopsy, were classified with Child's grading and separated by habits of alcohol intake, less and greater than 20g/day. No significant differences were observed about genotype but genotypes A and D were predominant in both of them. A higher percentage of males (P<.001) were observed in the group with alcohol intake above 20g/day, as well a lower proportion of patients with HBeAg negativity (P< or =.035). In this group, biochemistry parameters, such as alanine aminotransferase (P=.006), aspartate aminotransferase (P=.001), gamma-glutamyl transferase (P<.001) were elevated in a significantly higher proportion than in the other group. The analysis of hematological parameters showed significantly lower values of platelets (P=.042) and mean corpuscular volume (P<.001) and significantly higher values of prothrombin time (P<.001) in the group with higher levels of alcohol consumption. The characteristics of biopsy (P<.001) and Child-Phug's classification (P=.002) revealed more severe results in this group. Logistic regression showed a positive association between liver damage and alcohol intake, increasing with age. In female patients, a strong positive association between alcohol intake and liver damage was also found (odds ratio: 9.379; 95% confidence interval: 0.859-468.422; P = .037); however, the most severe cases were only observed in women older than 45 years. In patients with HBV infection, alcohol is associated with a more severe liver disease. No evidence was found

  20. [Fulminant hepatitis induced by disulfiram in a patient with alcoholic cirrhosis. Survival after liver transplantation].

    PubMed

    Vanjak, D; Samuel, D; Gosset, F; Derrida, S; Moreau, R; Soupison, T; Soulier, A; Bismuth, H; Sicot, C

    1989-12-01

    Fulminant hepatitis was observed in a 44-year-old patient with cirrhosis, 38 days after the beginning of a treatment by disulfiram. Hepatitis was associated with fever and hypereosinophilia. Liver transplantation was performed with success. We reviewed 15 previously published cases of disulfiram-induced hepatitis. They occurred from 10 to 180 days after the beginning of the treatment by disulfiram, aminotransferases were increased whereas alkaline phosphatases were not markedly changed; there was either focal or widespread necrosis. Fulminant hepatitis was observed mainly in patients with alcoholic chronic liver disease or in patients who continued to ingest disulfiram while jaundice was already present. An immunoallergic mechanism is thought to be responsible for disulfiram-induced hepatitis. PMID:2625187

  1. Chronic alcohol intake upregulates hepatic expression of carotenoid cleavage enzymes and PPAR in rats.

    PubMed

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

    2010-10-01

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

  2. Behavioral Interventions to Reduce Alcohol Use Among Patients with Hepatitis C: A Systematic Review.

    PubMed

    Sims, Omar T; Maynard, Quentin R; Melton, Pam A

    2016-10-01

    Alcohol use is a barrier to pharmacologic treatment for hepatitis C virus (HCV). It is advantageous for medical and clinical social workers engaged in HCV care to be knowledgeable of behavioral interventions that can be used to reduce alcohol use among patients with HCV. This article identifies and describes studies that designed and implemented behavioral interventions to reduce alcohol use among patients with HCV in clinical settings. To achieve this goal, this article conducts a rigorous systematic review to identify peer-reviewed articles, describes each behavioral intervention, and reports primary outcomes of each study included in the review. PMID:27295132

  3. Hepatitis B vaccination. Response of alcoholic with and without liver injury.

    PubMed

    Mendenhall, C; Roselle, G A; Lybecker, L A; Marshall, L E; Grossman, C J; Myre, S A; Weesner, R E; Morgan, D D

    1988-03-01

    Alcoholics are at risk to develop hepatitis B infections, chronic active hepatitis, and even hepatoma. Hence, immunization with hepatitis B vaccine is recommended. However, immune abnormalities may coexist which alter their responsiveness to vaccination. This study compares the immune response to this vaccine in controls (group I), alcoholics without overt liver disease (group II), and alcoholics with clinical liver disease (group III). By the seventh month after the initial vaccination, 89% in group I, 70% in group II, and 18% in group III had a response greater than 36 RIA units. The magnitude of the response was significantly different in groups I, II, and III (19,456 vs 8,326 vs 153 RIA units, respectively; P less than 0.05, group I vs III). In those who did not respond, a significant (P less than 0.02) lower helper/inducer (T4) class of lymphocytes was observed as compared to patients who exhibited an adequate response. These observations suggest: (1) that the response to hepatitis B vaccine is a T-cell-dependent event and (2) that in this population, using the existing vaccine, postvaccination evaluations of antibody concentrations are needed before protection against hepatitis B infection can be assumed. PMID:2856849

  4. The association of syphilis with cirrhosis: the role of alcohol and serum hepatitis

    PubMed Central

    Sadikali, F.

    1975-01-01

    The role of syphilis and alcohol was investigated in a prospective study of patients with cirrhosis of liver in Uganda, and results were correlated with the histological type of cirrhosis, and serological tests for hepatitis B antigen (HB Ag). Eighteen out of eighty (22·5%) patients with histologically-proven cirrhosis had positive serology for syphilis (VDRL and TPI). A high incidence of alcoholism (80%) and syphilis (60%) was found in patients with micronodular cirrhosis who were all negative for HB Ag. By contrast, HB Ag was detected in 37% of patients with macronodular cirrhosis who had a much smaller incidence of syphilis and alcoholism. Although chronic infection with hepatitis B virus related to HB Ag appears to be an important factor in the pathogenesis of cirrhosis in at least 30% of cases, infection acquired during past treatment for syphilis is not an important cause of the association of syphilis with cirrhosis in this population. Subdivision of patients with cirrhosis into those with and those without a history of severe alcohol abuse showed that the difference between the incidence of syphilis in the two groups is significant statistically. However, evidence of syphilis in association with non-alcoholic as well as alcoholic cirrhosis in this and other previously reported series suggests that the association between the two diseases cannot be entirely explained through the common factor of alcoholism, and other factors may also be responsible. PMID:1114150

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

    SciTech Connect

    Lieber, Charles S. Leo, Maria Anna; Wang, Xiaolei; DeCarli, Leonore M.

    2008-08-22

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

  6. Binding of aromatic amines to the rat hepatic Ah receptor in vitro and in vivo and the 8S and 4S estrogen receptor of rat uterus and rat liver

    SciTech Connect

    Cikryt, P.; Kaiser, T.; Gottlicher, M. )

    1990-08-01

    Studies on structurally related aromatic amines with different carcinogenic properties have shown that 2-acetylaminofluorene (2-AAF) and 2-acetylaminophenanthrene (AAP) inhibit the binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin to the Ah receptor in vitro. The apparent inhibitor constants (K{sub i}) are 2.3 {mu}M for 2-AAF and 2.7 {mu}M for AAP. In contrast, 4-acetylaminofluorene, an isomer of 2-AAF, and trans-4-acetylaminostilbene do not bind to the rat hepatic cytosolic Ah receptor. Pretreating female Wistar rats with 2-AAF or AAP leads to the induction of the P-450 isoenzymes that are under the control of the Ah receptor. Ornithine decarboxylase activity is induced by all aromatic amines tested irrespective of their Ah receptor affinity. The aromatic amines used as model compounds do not inhibit the binding of 17-{beta}-estradiol to the 8S and 4S estrogen receptor of rat uterus or rat liver in a competition assay analyzed using sucrose density gradient centrifugation. On the other hand, the aromatic amines bind to varying extents to another estrogen-binding protein of rat liver whose function and identity is still unknown. The study demonstrates that structurally related aromatic amines in their unmetabolized form interact differentially with a cellular target protein, the Ah receptor, in vitro as well as in vivo. However, a relationship between these effects and the postulated promoting properties of 2-AAF remains to be established.

  7. Frequency of alcohol and smoking cessation counseling in hepatitis C patients among internists and gastroenterologists.

    PubMed

    Chandra, Tanu; Reyes, Mary; Nguyen, Huy; Borum, Marie

    2009-12-21

    Given the overwhelming evidence that both alcohol consumption and smoking accelerate the progression of hepatitis C virus (HCV)-induced liver disease, we evaluated the frequency of alcohol and smoking counseling of patients with HCV-induced liver disease by their primary care internists and gastroenterologists. One hundred and twenty-three medical records of consecutive patients with HCV-induced liver disease referred by an internist to a gastroenterologist for its management were reviewed. Patient gender, race, history of and counseling against alcohol and tobacco use by a physician and a gastroenterologist were obtained. A database was created using Microsoft Excel. There were 105 African-Americans, 12 Caucasians and six patients of other races/ethnicities. Forty-six (37%) patients were daily tobacco users and 34 (28%) patients were daily alcohol consumers. There was a statistically significant difference in the frequencies of alcohol (P = 0.0002) and smoking cessation (P = 0.0022) between gastroenterologists and internists. This study reveals that internists and gastroenterologists, alike, inadequately counsel patients with hepatitis C about tobacco and alcohol use. PMID:20014469

  8. Suppression of PPARγ-mediated monoacylglycerol O-acyltransferase 1 expression ameliorates alcoholic hepatic steatosis.

    PubMed

    Yu, Jung Hwan; Song, Su Jin; Kim, Ara; Choi, Yoonjeong; Seok, Jo Woon; Kim, Hyo Jung; Lee, Yoo Jeong; Lee, Kwan Sik; Kim, Jae-Woo

    2016-01-01

    Alcohol consumption is one of the major causes of hepatic steatosis, fibrosis, cirrhosis, and superimposed hepatocellular carcinoma. Ethanol metabolism alters the NAD(+)/NADH ratio, thereby suppressing the activity of sirtuin family proteins, which may affect lipid metabolism in liver cells. However, it is not clear how long-term ingestion of ethanol eventually causes lipid accumulation in liver. Here, we demonstrate that chronic ethanol ingestion activates peroxisome proliferator-activated receptor γ (PPARγ) and its target gene, monoacylglycerol O-acyltransferase 1 (MGAT1). During ethanol metabolism, a low NAD(+)/NADH ratio repressed NAD-dependent deacetylase sirtuin 1 (SIRT1) activity, concomitantly resulting in increased acetylated PPARγ with high transcriptional activity. Accordingly, SIRT1 transgenic mice exhibited a low level of acetylated PPARγ and were protected from hepatic steatosis driven by alcohol or PPARγ2 overexpression, suggesting that ethanol metabolism causes lipid accumulation through activation of PPARγ through acetylation. Among the genes induced by PPARγ upon alcohol consumption, MGAT1 has been shown to be involved in triglyceride synthesis. Thus, we tested the effect of MGAT1 knockdown in mice following ethanol consumption, and found a significant reduction in alcohol-induced hepatic lipid accumulation. These results suggest that MGAT1 may afford a promising approach to the treatment of fatty liver disease. PMID:27404390

  9. Suppression of PPARγ-mediated monoacylglycerol O-acyltransferase 1 expression ameliorates alcoholic hepatic steatosis

    PubMed Central

    Yu, Jung Hwan; Song, Su Jin; Kim, Ara; Choi, Yoonjeong; Seok, Jo Woon; Kim, Hyo Jung; Lee, Yoo Jeong; Lee, Kwan Sik; Kim, Jae-woo

    2016-01-01

    Alcohol consumption is one of the major causes of hepatic steatosis, fibrosis, cirrhosis, and superimposed hepatocellular carcinoma. Ethanol metabolism alters the NAD+/NADH ratio, thereby suppressing the activity of sirtuin family proteins, which may affect lipid metabolism in liver cells. However, it is not clear how long-term ingestion of ethanol eventually causes lipid accumulation in liver. Here, we demonstrate that chronic ethanol ingestion activates peroxisome proliferator-activated receptor γ (PPARγ) and its target gene, monoacylglycerol O-acyltransferase 1 (MGAT1). During ethanol metabolism, a low NAD+/NADH ratio repressed NAD-dependent deacetylase sirtuin 1 (SIRT1) activity, concomitantly resulting in increased acetylated PPARγ with high transcriptional activity. Accordingly, SIRT1 transgenic mice exhibited a low level of acetylated PPARγ and were protected from hepatic steatosis driven by alcohol or PPARγ2 overexpression, suggesting that ethanol metabolism causes lipid accumulation through activation of PPARγ through acetylation. Among the genes induced by PPARγ upon alcohol consumption, MGAT1 has been shown to be involved in triglyceride synthesis. Thus, we tested the effect of MGAT1 knockdown in mice following ethanol consumption, and found a significant reduction in alcohol-induced hepatic lipid accumulation. These results suggest that MGAT1 may afford a promising approach to the treatment of fatty liver disease. PMID:27404390

  10. Hepatic non-parenchymal cells: Master regulators of alcoholic liver disease?

    PubMed Central

    Seo, Wonhyo; Jeong, Won-Il

    2016-01-01

    Chronic alcohol consumption is one of the most common causes of the progression of alcoholic liver disease (ALD). In the past, alcohol-mediated hepatocyte injury was assumed to be a significantly major cause of ALD. However, a huge number of recent and brilliant studies have demonstrated that hepatic non-parenchymal cells including Kupffer cells, hepatic stellate cells, liver sinusoidal endothelial cells and diverse types of lymphocytes play crucial roles in the pathogenesis of ALD by producing inflammatory mediators such as cytokines, oxidative stress, microRNA, and lipid-originated metabolites (retinoic acid and endocannabinoids) or by directly interacting with parenchymal cells (hepatocytes). Therefore, understanding the comprehensive roles of hepatic non-parenchymal cells during the development of ALD will provide new integrative directions for the treatment of ALD. This review will address the roles of non-parenchymal cells in alcoholic steatosis, inflammation, and liver fibrosis and might help us to discover possible therapeutic targets and treatments involving modulating the non-parenchymal cells in ALD. PMID:26819504

  11. Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease.

    PubMed

    Kawano, Yuki; Cohen, David E

    2013-04-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation in the absence of excess alcohol intake. NAFLD is the most common chronic liver disease, and ongoing research efforts are focused on understanding the underlying pathobiology of hepatic steatosis with the anticipation that these efforts will identify novel therapeutic targets. Under physiological conditions, the low steady-state triglyceride concentrations in the liver are attributable to a precise balance between acquisition by uptake of non-esterified fatty acids from the plasma and by de novo lipogenesis, versus triglyceride disposal by fatty acid oxidation and by the secretion of triglyceride-rich lipoproteins. In NAFLD patients, insulin resistance leads to hepatic steatosis by multiple mechanisms. Greater uptake rates of plasma non-esterified fatty acids are attributable to increased release from an expanded mass of adipose tissue as a consequence of diminished insulin responsiveness. Hyperinsulinemia promotes the transcriptional upregulation of genes that promote de novo lipogenesis in the liver. Increased hepatic lipid accumulation is not offset by fatty acid oxidation or by increased secretion rates of triglyceride-rich lipoproteins. This review discusses the molecular mechanisms by which hepatic triglyceride homeostasis is achieved under normal conditions, as well as the metabolic alterations that occur in the setting of insulin resistance and contribute to the pathogenesis of NAFLD. PMID:23397118

  12. Hepatic Steatosis in Response to Acute Alcohol Exposure in Zebrafish requires Srebp Activation

    PubMed Central

    Passeri, Michael J.; Cinaroglu, Ayca; Gao, Chuan; Sadler, Kirsten C.

    2008-01-01

    Steatosis is the most common consequence of acute alcohol abuse and may predispose to more severe hepatic disease. Increased lipogenesis driven by the sterol response element binding protein (SREBP) transcription factors is essential for steatosis associated with chronic alcohol ingestion, but the mechanisms underlying steatosis following acute alcohol exposure are unknown. Zebrafish larvae represent an attractive vertebrate model for studying alcoholic liver disease (ALD), because they possess the pathways to metabolize alcohol, the liver is mature by 4 days post-fertilization (dpf), and alcohol can be simply added to their water. Exposing 4 dpf zebrafish larvae to 2% ethanol (EtOH) for 32 hours achieves ∼80 mM intracellular EtOH and upregulation of hepatic cyp2e1, sod and bip, indicating that EtOH is metabolized and provokes oxidant stress. EtOH-treated larvae develop hepatomegaly and steatosis accompanied by changes in the expression of genes required for hepatic lipid metabolism. Based on the importance of SREPBs in chronic ALD, we explored the role of Srebps in this model of acute ALD. Srebp activation was prevented in gonzo larvae, which harbor a mutation in the membrane bound transcription factor protease 1 (mbtps1) gene, and in embryos injected with a morpholino to knock-down Srebp cleavage activating protein (scap). Both gonzo mutants and scap morphants were resistant to steatosis in response to 2% EtOH, and the expression of many Srebp target genes are down regulated in gonzo mutant livers. Conclusion Zebrafish larvae develop signs of acute ALD, including steatosis. Srebp activation is required for steatosis in this model. The tractability of zebrafish genetics provides a valuable tool for dissecting the molecular pathogenesis of acute ALD. PMID:19127516

  13. Deletion of tumor progression locus 2 attenuates alcohol-induced hepatic inflammation

    PubMed Central

    Stice, Camilla P.; Hussain, Sajid; Liu, Chun; Ausman, Lynne M.

    2016-01-01

    Background The pathogenesis of alcoholic liver disease (ALD) involves the interaction of several inflammatory signaling pathways. Tumor progression locus 2 (TPL2), also known as Cancer Osaka Thyroid (COT) and MAP3K8, is a serine-threonine kinase that functions as a critical regulator of inflammatory pathways by up-regulating production of inflammatory cytokines. The present study aims to fill the gap in knowledge regarding the involvement of TPL2 in the mechanism of alcohol-induced hepatic inflammation. Methods Male TPL2−/− knockout (TPL2KO) mice and TPL2+/+ wild-type (WT) mice were group pair-fed with Lieber-DeCarli liquid ethanol diet (EtOH diet, 27% energy from EtOH) or control diet (ctrl diet) for 4 weeks. Both histological and molecular biomarkers involved in the induction of hepatic inflammation by alcohol consumption were examined. Results Consumption of the EtOH diet in WT mice lead to a significant induction of TPL2 mRNA expression as compared with WT mice fed ctrl diet. A significant induction in inflammatory foci and steatosis was also observed in WT mice fed EtOH diet. The deletion of TPL2 significantly reduced inflammatory foci in the liver of mice consuming both ctrl and EtOH diets as compared to their respective WT controls. This reduction was associated with suppression of hepatic inflammatory gene expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) and macrophage marker F4/80. In addition, histological analysis of livers revealed that TPL2 deletion resulted in reduced steatosis in both ctrl (significant) and EtOH (non-significant) diet-fed mice as compared to their respective WT controls. Conclusions The demonstration that TPL2 deletion attenuates alcohol-induced hepatic inflammation provides evidence of a novel role for TPL2 in the pathogenesis of ALD. PMID:26904554

  14. Clinical assessment of hepatic de novo lipogenesis in non-alcoholic fatty liver disease.

    PubMed

    Paglialunga, Sabina; Dehn, Clayton A

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is heralded as the next big global epidemic. Hepatic de novo lipogenesis (DNL), the synthesis of new fatty acids from non-lipid sources, is thought to play a pivotal role in the development of NAFLD. While there is currently no NAFLD-specific therapeutic agent available, pharmaceutical drugs aimed at reducing hepatic fat accretion may prove to be a powerful ally in the treatment and management of this disease. With a focus on NAFLD, the present review summarizes current techniques examining DNL from a clinical perspective, and describes the merits and limitations of three commonly used assays; stable-label isotope tracer studies, fatty acid indexes and indirect calorimetry as non-invasive measures of hepatic DNL. Finally, the application of DNL assessments in the pharmacological and nutraceutical treatment of NAFLD/NASH is summarized. In a clinical research setting, measures of DNL are an important marker in the development of anti-NAFLD treatments.

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

    SciTech Connect

    Kaphalia, Bhupendra S.; Bhopale, Kamlesh K.; Kondraganti, Shakuntala; Wu Hai; Boor, Paul J.; Ansari, G.A. Shakeel

    2010-08-01

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

  16. Tlr4-mutant mice are resistant to acute alcohol-induced sterol-regulatory element binding protein activation and hepatic lipid accumulation.

    PubMed

    Zhang, Zhi-Hui; Liu, Xiao-Qian; Zhang, Cheng; He, Wei; Wang, Hua; Chen, Yuan-Hua; Liu, Xiao-Jing; Chen, Xi; Xu, De-Xiang

    2016-01-01

    Previous studies demonstrated that acute alcohol intoxication caused hepatic lipid accumulation. The present study showed that acute alcohol intoxication caused hepatic lipid accumulation in Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic sterol-regulatory element binding protein (SREBP)-1, a transcription factor regulating fatty acid and triglyceride (TG) synthesis, was activated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic Fas, Acc, Scd-1 and Dgat-2, the key genes for fatty acid and TG synthesis, were up-regulated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Additional experiment showed that hepatic MyD88 was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic NF-κB was activated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Moreover, hepatic GSH content was reduced and hepatic MDA level was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic CYP2E1 was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic p67phox and gp91phox, two NADPH oxidase subunits, were up-regulated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Alpha-phenyl-N-t-butylnitrone (PBN), a free radical spin-trapping agent, protected against alcohol-induced hepatic SREBP-1 activation and hepatic lipid accumulation. In conclusion, Tlr4-mutant mice are resistant to acute alcohol-induced hepatic SREBP-1 activation and hepatic lipid accumulation. PMID:27627966

  17. Tlr4-mutant mice are resistant to acute alcohol-induced sterol-regulatory element binding protein activation and hepatic lipid accumulation

    PubMed Central

    Zhang, Zhi-Hui; Liu, Xiao-Qian; Zhang, Cheng; He, Wei; Wang, Hua; Chen, Yuan-Hua; Liu, Xiao-Jing; Chen, Xi; Xu, De-Xiang

    2016-01-01

    Previous studies demonstrated that acute alcohol intoxication caused hepatic lipid accumulation. The present study showed that acute alcohol intoxication caused hepatic lipid accumulation in Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic sterol-regulatory element binding protein (SREBP)-1, a transcription factor regulating fatty acid and triglyceride (TG) synthesis, was activated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic Fas, Acc, Scd-1 and Dgat-2, the key genes for fatty acid and TG synthesis, were up-regulated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Additional experiment showed that hepatic MyD88 was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic NF-κB was activated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Moreover, hepatic GSH content was reduced and hepatic MDA level was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic CYP2E1 was elevated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Hepatic p67phox and gp91phox, two NADPH oxidase subunits, were up-regulated in alcohol-treated Tlr4-wild-type mice but not in Tlr4-mutant mice. Alpha-phenyl-N-t-butylnitrone (PBN), a free radical spin-trapping agent, protected against alcohol-induced hepatic SREBP-1 activation and hepatic lipid accumulation. In conclusion, Tlr4-mutant mice are resistant to acute alcohol-induced hepatic SREBP-1 activation and hepatic lipid accumulation. PMID:27627966

  18. Hepatic Deficiency of Augmenter of Liver Regeneration Exacerbates Alcohol-Induced Liver Injury and Promotes Fibrosis in Mice.

    PubMed

    Kumar, Sudhir; Wang, Jiang; Rani, Richa; Gandhi, Chandrashekhar R

    2016-01-01

    Why only a subpopulation (about 15%) of humans develops liver cirrhosis due to alcohol is a critical as yet unanswered question. Liver-specific depletion of augmenter of liver regeneration (ALR) protein in mice causes robust steatosis and hepatocyte apoptosis by 2 weeks; these pathologies regress subsequently with return of ALR expression even at lower than control levels, but the mice develop modest steatohepatitis by 8 weeks. We aimed to investigate whether chronic alcohol ingestion promotes excessive hepatic fibrosis in these ALR-deficient mice. Liver-specific ALR-deficient and wild type (WT) female mice (8-10 weeks old) were placed on 4% alcohol-supplemented or isocaloric diet for 4 weeks. Liver sections were examined for histopathology, and parameters of steatosis and fibrosis were quantified. The mRNA expression of alcohol dehydrogenase-1, acetaldehyde dehydrogenase-1 and cytochrome P450-2E1 increased in WT mice but decreased in ALR-deficient mice upon alcohol ingestion. While alcohol induced steatosis and mild inflammation in WT mice, ALR-deficient mice showed minimal steatosis, strong hepatocellular injury and inflammation, prominent ductular proliferation, and robust fibrosis. Compared to the WT mice, alcohol feeding of ALR-deficient mice resulted in significantly greater increase in hepatic TNFα and TGFβ, and oxidative stress; there was also hepatic iron accumulation, robust lipid peroxidation and mitochondrial DNA damage. Importantly, similar to ALR-deficient mice, lower hepatic ALR levels in human alcoholic liver cirrhosis were associated with increased iron content, reduced expression of alcohol dehydrogenase and acetaldehyde dehydrogenase, and elevated fibrogenic markers. We conclude that ALR deficiency or anomaly can play a critical role in alcohol-induced hepatic fibrosis/cirrhosis, mechanisms of which may involve dysregulation of alcohol metabolism and iron homeostasis, mitochondrial damage and oxidative injury. PMID:26808690

  19. Hepatic Deficiency of Augmenter of Liver Regeneration Exacerbates Alcohol-Induced Liver Injury and Promotes Fibrosis in Mice

    PubMed Central

    Kumar, Sudhir; Wang, Jiang; Rani, Richa; Gandhi, Chandrashekhar R.

    2016-01-01

    Why only a subpopulation (about 15%) of humans develops liver cirrhosis due to alcohol is a critical as yet unanswered question. Liver-specific depletion of augmenter of liver regeneration (ALR) protein in mice causes robust steatosis and hepatocyte apoptosis by 2 weeks; these pathologies regress subsequently with return of ALR expression even at lower than control levels, but the mice develop modest steatohepatitis by 8 weeks. We aimed to investigate whether chronic alcohol ingestion promotes excessive hepatic fibrosis in these ALR-deficient mice. Liver-specific ALR-deficient and wild type (WT) female mice (8–10 weeks old) were placed on 4% alcohol-supplemented or isocaloric diet for 4 weeks. Liver sections were examined for histopathology, and parameters of steatosis and fibrosis were quantified. The mRNA expression of alcohol dehydrogenase-1, acetaldehyde dehydrogenase-1 and cytochrome P450-2E1 increased in WT mice but decreased in ALR-deficient mice upon alcohol ingestion. While alcohol induced steatosis and mild inflammation in WT mice, ALR-deficient mice showed minimal steatosis, strong hepatocellular injury and inflammation, prominent ductular proliferation, and robust fibrosis. Compared to the WT mice, alcohol feeding of ALR-deficient mice resulted in significantly greater increase in hepatic TNFα and TGFβ, and oxidative stress; there was also hepatic iron accumulation, robust lipid peroxidation and mitochondrial DNA damage. Importantly, similar to ALR-deficient mice, lower hepatic ALR levels in human alcoholic liver cirrhosis were associated with increased iron content, reduced expression of alcohol dehydrogenase and acetaldehyde dehydrogenase, and elevated fibrogenic markers. We conclude that ALR deficiency or anomaly can play a critical role in alcohol-induced hepatic fibrosis/cirrhosis, mechanisms of which may involve dysregulation of alcohol metabolism and iron homeostasis, mitochondrial damage and oxidative injury. PMID:26808690

  20. Transient Receptor Potential Vanilloid 1 Gene Deficiency Ameliorates Hepatic Injury in a Mouse Model of Chronic Binge Alcohol-Induced Alcoholic Liver Disease

    PubMed Central

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

    2016-01-01

    Experimental alcohol-induced liver injury is exacerbated by a high polyunsaturated fat diet rich in linoleic acid. We postulated that bioactive oxidized linoleic acid metabolites (OXLAMs) play a critical role in the development/progression of alcohol-mediated hepatic inflammation and injury. OXLAMs are endogenous ligands for transient receptor potential vanilloid 1 (TRPV1). Herein, we evaluated the role of signaling through TRPV1 in an experimental animal model of alcoholic liver disease (ALD). Chronic binge alcohol administration increased plasma OXLAM levels, specifically 9- and 13-hydroxy-octadecadienoic acids. This effect was associated with up-regulation of hepatic TRPV1. Exposure of hepatocytes to these OXLAMs in vitro resulted in activation of TRPV1 signal transduction with increased intracellular Ca2+ levels. Genetic depletion of TRPV1 did not blunt hepatic steatosis caused by ethanol, but prevented hepatic injury. TRPV1 deficiency protected from hepatocyte death and prevented the increase in proinflammatory cytokine and chemokine expression, including tumor necrosis factor-α, IL-6, macrophage inflammatory protein-2, and monocyte chemotactic protein 1. TRPV1 depletion markedly blunted ethanol-mediated induction of plasminogen activator inhibitor-1, an important alcohol-induced hepatic inflammation mediator, via fibrin accumulation. This study indicates, for the first time, that TRPV1 receptor pathway may be involved in hepatic inflammatory response in an experimental animal model of ALD. TRPV1-OXLAM interactions appear to play a significant role in hepatic inflammation/injury, further supporting an important role for dietary lipids in ALD. PMID:25447051

  1. Systematic review of the pharmacological treatment of alcohol use disorders in individuals infected with hepatitis C.

    PubMed

    Thibault, Alexis; Brissette, Suzanne; Jutras-Aswad, Didier

    2015-01-01

    Treating alcohol use disorders (AUD) is critical in individuals suffering from hepatitis C infection (HCV). Aside from psychosocial interventions, pharmacological treatment is effective for decreasing alcohol consumption and promoting abstinence. However, unique factors belonging to HCV-infected individuals, such as baseline hepatic vulnerability and possible ongoing hepatitis C treatment, complicate AUD drug therapy. The goal of this review is to systematically identify, summarize, and evaluate the existing evidence on the pharmacological management of AUD in HCV-infected individuals. MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials were searched for English- and French-language articles published from 1993 to December 2013. The search criteria focused on clinical trials and observational studies assessing the efficacy and/or safety of pharmacological management of AUD in patients infected with HCV. Of 421 identified studies, three were included for analysis. Two were observational studies assessing the safety of disulfiram. One was a randomized controlled trial assessing the efficacy and safety of baclofen. There is paucity of data regarding the efficacy and safety of pharmacological treatment of AUD in HCV-infected individuals, with studies being small series and showing significant heterogeneity. No strong recommendations can be made based on the current studies as to which pharmacological option should be preferred in this sub-population. PMID:25928362

  2. Hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) infections in alcoholics.

    PubMed

    Prakash, Om; Mason, Andrew; Luftig, Ronald B; Bautista, Abraham P

    2002-07-01

    Approximately 400,000 individuals in the United States are co-infected with hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) and it is likely that almost one in two of these subjects consumes alcohol. The majority of these patients suffer an accelerated course of liver disease as manifested by the onset of cirrhosis within 5 to 10 years of developing HCV infection, as well as an increased risk of developing hepatocellular carcinoma (HCC). It is thought that chronic alcohol abuse mediates liver damage as a result of increased production of free radicals and proinflammatory cytokines. In the setting of chronic HCV infection, alcohol ingestion has an additional effect of diminishing immune clearance and increasing viral burden to hasten the onset of cirrhosis and HCC. Likewise, chronic HCV and HIV-1 co-infection results in a net increase in HCV burden; higher prevalence rates of HCV transmission to sexual partners and offspring, as well as an accelerated progression to end stage liver disease as compared to individuals with HCV infection alone. Thus, the synergistic effects of alcohol abuse and HIV-1 greatly impact on the morbidity and mortality for patients with HCV coinfection. Ultimately, this cumulative disease process will require far more aggressive management with abstinence and counseling for alcohol abuse; highly active antiretroviral therapy (HAART) for HIV infection and combination anti-viral therapy for HCV infection to stem the rapid progression to end stage liver disease. PMID:12086918

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

    SciTech Connect

    Lieber, Charles S. Leo, Maria A.; Wang Xiaolei; DeCarli, Leonore M.

    2008-05-23

    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.

  4. Aberrant Hepatic Methionine Metabolism and Gene Methylation in the Pathogenesis and Treatment of Alcoholic Steatohepatitis

    PubMed Central

    Halsted, Charles H.; Medici, Valentina

    2012-01-01

    The pathogenesis of alcoholic steatohepatitis (ASH) involves ethanol-induced aberrations in hepatic methionine metabolism that decrease levels of S-adenosylmethionine (SAM), a compound which regulates the synthesis of the antioxidant glutathione and is the principal methyl donor in the epigenetic regulation of genes relevant to liver injury. The present paper describes the effects of ethanol on the hepatic methionine cycle, followed by evidence for the central role of reduced SAM in the pathogenesis of ASH according to clinical data and experiments in ethanol-fed animals and in cell models. The efficacy of supplemental SAM in the prevention of ASH in animal models and in the clinical treatment of ASH will be discussed. PMID:22007317

  5. Hepatitis

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Hepatitis KidsHealth > For Kids > Hepatitis Print A A A ... an important digestive liquid called bile . What Is Hepatitis? Hepatitis is an inflammation (say: in-fluh-MAY- ...

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

    PubMed Central

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

    2014-01-01

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

  7. Clinical assessment of hepatic de novo lipogenesis in non-alcoholic fatty liver disease.

    PubMed

    Paglialunga, Sabina; Dehn, Clayton A

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is heralded as the next big global epidemic. Hepatic de novo lipogenesis (DNL), the synthesis of new fatty acids from non-lipid sources, is thought to play a pivotal role in the development of NAFLD. While there is currently no NAFLD-specific therapeutic agent available, pharmaceutical drugs aimed at reducing hepatic fat accretion may prove to be a powerful ally in the treatment and management of this disease. With a focus on NAFLD, the present review summarizes current techniques examining DNL from a clinical perspective, and describes the merits and limitations of three commonly used assays; stable-label isotope tracer studies, fatty acid indexes and indirect calorimetry as non-invasive measures of hepatic DNL. Finally, the application of DNL assessments in the pharmacological and nutraceutical treatment of NAFLD/NASH is summarized. In a clinical research setting, measures of DNL are an important marker in the development of anti-NAFLD treatments. PMID:27640119

  8. Pioglitazone, quercetin and hydroxy citric acid effect on hepatic biomarkers in Non Alcoholic Steatohepatitis

    PubMed Central

    Surapaneni, Krishna Mohan; Jainu, Mallika

    2014-01-01

    Background: Non alcoholic steatohepatitis (NASH), severe form of diseases belonging to the spectrum of the Non alcoholic fatty liver disease (NAFLD). It is an asymptomatic disease which leads to fibrosis and finally to cirrhosis, an end stage liver disease. Objective: To study the effect of pioglitazone, quercetin and hydroxy citric acid on hepatic biomarkers and various biochemical parameters in experimentally induced non alcoholic steatohepatitis (NASH). Materials and Methods: Male Wister rats were divided into 8 groups. The activities of alkaline phosphatase (ALP), aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH) and γ-Glutamyl Transferase (GGT) were assayed in serum. The levels of various other biochemical parameters such as serum albumin, total bilirubin, creatinine, urea, uric acid and glucose were also estimated in experimental NASH. Results: The NASH group produced severe liver injury by significantly increasing the serum levels of ALT, AST, GGT and LDH compared with that of the control. However, the experimental NASH rats treated with pioglitazone, with quercetin and with hydroxy citric acid showed an obvious decrease in ALT, AST, GGT and LDH levels when compared with that of NASH induced group. A significant increase in the levels of albumin, creatinine, urea, uric acid, glucose and total bilirubin was noticed in experimentally induced NASH group (group 2) when compared to rats in control group (group 1). Conclusion: It could be inferred from this study that, pioglitazone, quercetin and hydroxy citric acid may afford protection to the liver against NASH, as evidenced by the results of this study on the levels of various biochemical parameters such as glucose, urea, uric acid, creatinine and bilirubin. Whereas from the results of hepatic marker enzymes, it is evident that optimal protection was observed after quercetin treatment against experimental NASH whereas pioglitazone and hydroxy citric acid also confers

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

    PubMed Central

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

    2016-01-01

    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 micro-tubules 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

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

    PubMed

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

    2015-02-15

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

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

    PubMed Central

    Ye, Qinyuan; Lian, Fuzhi; Chavez, Pollyanna R.G.; Chung, Jayong; Ling, Wenhua; Qin, Hua; Seitz, Helmut K.

    2012-01-01

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

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

    SciTech Connect

    Wu, Weibin; Zhu, Bo; Peng, Xiaomin; Zhou, Meiling; Jia, Dongwei; Gu, Jianxin

    2014-01-03

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

  13. Prognostic significance of cholestatic alcoholic hepatitis. VA Cooperative Study Group #119.

    PubMed

    Nissenbaum, M; Chedid, A; Mendenhall, C; Gartside, P

    1990-07-01

    Tissue cholestasis is a histologic feature in some patients with alcoholic liver disease, but its significance is unknown. We studied prospectively the clinical, laboratory, and histologic findings of 306 chronic male alcoholics in whom liver tissue was available. Tissue cholestasis permitted identification of two groups: group I, absent or mild cholestasis (239 patients), and group II, moderate to severe cholestasis (67 patients). Statistical evaluation was performed by Student's t test and regression analyses. In patients with tissue cholestasis, 97% had elevated serum cholylglycine levels, while only 61% had significant jaundice (serum bilirubin greater than 5 mg/dl). In patients without tissue cholestasis, 66% had elevated serum cholylglycine and 13.5% jaundice. Highly significant statistical correlations (P less than 0.0001) were found between cholestasis and malnutrition, prothrombin time, AST, alkaline phosphatase, bilirubin, Maddrey's discriminant function, serum cholylglycine level, albumin, and histologic severity score. In group I, 54% survived 60 months versus 22% in group II (P less than 0.0001). Highly significant statistical correlations (P less than 0.0001) were noted between serum cholylglycine levels and the parameters enumerated earlier, but not with survival. We conclude that tissue cholestasis is a highly significant prognostic indicator of outcome in alcoholic hepatitis and is more consistently associated with bile salt retention than jaundice.

  14. Diagnosis and Management of Alcoholic Liver Disease

    PubMed Central

    Dugum, Mohannad; McCullough, Arthur

    2015-01-01

    Alcohol is a leading cause of liver disease and is associated with significant morbidity and mortality. Several factors, including the amount and duration of alcohol consumption, affect the development and progression of alcoholic liver disease (ALD). ALD represents a spectrum of liver pathology ranging from fatty change to fibrosis to cirrhosis. Early diagnosis of ALD is important to encourage alcohol abstinence, minimize the progression of liver fibrosis, and manage cirrhosis-related complications including hepatocellular carcinoma. A number of questionnaires and laboratory tests are available to screen for alcohol intake. Liver biopsy remains the gold-standard diagnostic tool for ALD, but noninvasive accurate alternatives, including a number of biochemical tests as well as liver stiffness measurement, are increasingly being utilized in the evaluation of patients with suspected ALD. The management of ALD depends largely on complete abstinence from alcohol. Supportive care should focus on treating alcohol withdrawal and providing enteral nutrition while managing the complications of liver failure. Alcoholic hepatitis (AH) is a devastating acute form of ALD that requires early recognition and specialized tertiary medical care. Assessment of AH severity using defined scoring systems is important to allocate resources and initiate appropriate therapy. Corticosteroids or pentoxifylline are commonly used in treating AH but provide a limited survival benefit. Liver transplantation represents the ultimate therapy for patients with alcoholic cirrhosis, with most transplant centers mandating a 6 month period of abstinence from alcohol before listing. Early liver transplantation is also emerging as a therapeutic measure in specifically selected patients with severe AH. A number of novel targeted therapies for ALD are currently being evaluated in clinical trials. PMID:26356792

  15. Hepatocyte-mediated cytotoxicity and host defense mechanisms in the alcohol-injured liver.

    PubMed

    McVicker, Benita L; Thiele, Geoffrey M; Tuma, Dean J; Casey, Carol A

    2014-09-01

    The consumption of alcohol is associated with many health issues including alcoholic liver disease (ALD). The natural history of ALD involves the development of steatosis, inflammation (steatohepatitis), fibrosis and cirrhosis. During the stage of steatohepatitis, the combination of inflammation and cellular damage can progress to a severe condition termed alcoholic hepatitis (AH). Unfortunately, the pathogenesis of AH remains uncharacterized. Some modulations have been identified in host defense and liver immunity mechanisms during AH that highlight the role of intrahepatic lymphocyte accumulation and associated inflammatory cytokine responses. Also, it is hypothesized that alcohol-induced injury to liver cells may significantly contribute to the aberrant lymphocytic distribution that is seen in AH. In particular, the regulation of lymphocytes by hepatocytes may be disrupted in the alcoholic liver resulting in altered immunologic homeostasis and perpetuation of disease. In recent studies, it was demonstrated that the direct killing of activated T lymphocytes by hepatocytes is facilitated by the asialoglycoprotein receptor (ASGPR). The ASGPR is a well-characterized glycoprotein receptor that is exclusively expressed by hepatocytes. This hepatic receptor is known for its role in the clearance of desialylated glycoproteins or cells, yet neither its physiological function nor its role in disease states has been determined. Interestingly, alcohol markedly impairs ASGPR function; however, the effect alcohol has on ASGPR-mediated cytotoxicity of lymphocytes remains to be elucidated. This review discusses the contribution of hepatocytes in immunological regulation and, importantly, how pathological effects of ethanol disrupt hepatocellular-mediated defense mechanisms.

  16. Human herpesvirus-6 has no apparent influence on course of HCV hepatitis, but may complicate HBV hepatitis and alcoholic liver disease. A pilot study.

    PubMed

    Rojo, Julieta; Simoes, Patricia; Krueger, Gerhard R F; Humberto, Cruz Ortiz; Ramon, Albert M

    2003-01-01

    Human herpesvirus-6 (HHV-6) is a widespread virus with occasional reactivation and a potential hepatotropism. The present study was undertaken to investigate the frequency of HHV-6 reactivation in viral (HCV, HBV) and alcoholic liver diseases and its implication for the course of the primary disease. Serological and immunohistochemical tests were done to document viral activity, hepatocellular apoptosis or proliferation, and autoantibody formation. While the course of HCV remains apparently uninfluenced by HHV-6, HBV hepatitis and alcoholic liver disease show a higher incidence of autoantibody formation if HHV-6 is present. The data of this pilot study warrant more extensive investigations of the clinical pathology of HHV-6 in liver diseases.

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed

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

    2013-11-01

    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.

  19. Prenatal 3,3',4,4',5-pentachlorobiphenyl exposure modulates induction of rat hepatic CYP 1A1, 1B1, and AhR by 7,12-dimethylbenz[a]anthracene

    SciTech Connect

    Wakui, Shin . E-mail: wakui@azabu-u.ac.jp; Yokoo, Kiyofumi; Takahashi, Hiroyuki; Muto, Tomoko; Suzuki, Yoshihiko; Kanai, Yoshikatsu; Hano, Hiroshi; Furusato, Masakuni; Endou, Hitoshi

    2006-02-01

    We previously reported the finding that prenatal exposure to a relatively low dose of PCB126 increases the rate of DMBA-induced rat mammary carcinoma, while a high dose decreased it. One of the most important factors determining the sensitivity to mammary carcinogenesis is the metabolic stage at administration of the carcinogenic agent. DMBA is a procarcinogen that recruits the host metabolism to yield its ultimate carcinogenic form, and CYP1A1 and CYP1B1 (CYP1) conduct this metabolism. We investigated the hepatic expression of CYP1 and AhR following oral administration of DMBA (100 mg/kg b.w.) (i.g.) to 50-day-old female Sprague-Dawley rats whose dams had been treated (i.g.) with 2.5 ng, 250 ng, 7.5 {mu}g of PCB126/kg or the vehicle on days 13 to 19 post-conception. Real-time quantitative RT-PCR analysis revealed that the prenatal exposure to a relatively low dose of PCB126 (the 250 ng group) prolonged the higher expression of CYP1A1, CYP1B1, and AhR mRNA, while prenatal exposure to a high dose of PCB126 (the 7.5 {mu}g group) prolonged the higher expression of CYP1A1 and AhR mRNA. Western blotting and immunohistochemical analyses were consistent with mRNAs changes. Because DMBA oxidation produces a highly mutagenic metabolite and is finally catalyzed by CYP1B1, a relatively low PCB126 dose might produce the biological character to potentially increase the risk of DMBA-induced mammary carcinoma.

  20. Dysregulation of hepatic cAMP levels via altered Pde4b expression plays a critical role in alcohol-induced steatosis.

    PubMed

    Avila, Diana V; Barker, David F; Zhang, JingWen; McClain, Craig J; Barve, Shirish; Gobejishvili, Leila

    2016-09-01

    Alcohol-induced hepatic steatosis is a significant risk factor for progressive liver disease. Cyclic adenosine monophosphate (cAMP) signalling has been shown to significantly regulate lipid metabolism; however, the role of altered cAMP homeostasis in alcohol-mediated hepatic steatosis has never been studied. Our previous work demonstrated that increased expression of hepatic phosphodiesterase 4 (Pde4), which specifically hydrolyses and decreases cAMP levels, plays a pathogenic role in the development of liver inflammation/injury. The aim of this study was to examine the role of PDE4 in alcohol-induced hepatic steatosis. C57BL/6 wild-type and Pde4b knockout (Pde4b(-/-) ) mice were pair-fed control or ethanol liquid diets. One group of wild-type mice received rolipram, a PDE4-specific inhibitor, during alcohol feeding. We demonstrate for the first time that an early increase in PDE4 enzyme expression and a resultant decrease in hepatic cAMP levels are associated with the significant reduction in carnitine palmitoyltransferase 1A (Cpt1a) expression. Notably, alcohol-fed (AF) Pde4b(-/-) mice and AF wild-type mice treated with rolipram had significantly lower hepatic free fatty acid content compared with AF wild-type mice. Importantly, PDE4 inhibition in alcohol-fed mice prevented the decrease in hepatic Cpt1a expression via the Pparα/Sirt1/Pgc1α pathway. These results demonstrate that the alcohol- induced increase in hepatic Pde4, specifically Pde4b expression, and compromised cAMP signalling predispose the liver to impaired fatty acid oxidation and the development of steatosis. Moreover, these data also suggest that hepatic PDE4 may be a clinically relevant therapeutic target for the treatment of alcohol-induced hepatic steatosis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:27287961

  1. High prevalence of alcohol use among hepatitis C virus antibody positive injection drug users in three US cities

    PubMed Central

    Campbell, Jennifer V.; Hagan, Holly; Latka, Mary H.; Garfein, Richard S.; Golub, Elizabeth T.; Coady, Micaela H.; Thomas, David L.; Strathdee, Steffanie A.

    2007-01-01

    Injection drug users (IDUs) acquire the majority of new hepatitis C virus (HCV) infections and frequently use alcohol. Alcohol abuse accelerates liver disease among HCV-infected persons, can reduce the effectiveness of treatment for HCV infection and may be a contraindication for HCV treatment. HCV seropositive, HIV-negative IDUs aged 18–35 years in Baltimore, New York City and Seattle who were enrolled in a behavioral risk-reduction intervention trial underwent computerized self-interviews to assess baseline alcohol use and dependence and medical history. We measured problem alcohol use using the 10-item Alcohol Use Disorders Identification Test (AUDIT) scale. Of 598 participants, 84% responded “false” to: “it is safe for a person with HCV to drink alcohol”. Problem drinking, defined as score ≥ 8 on AUDIT, was identified in 37%. Correlates of scoring ≥ 8 on AUDIT included homelessness, male gender, primarily injecting speedballs, having injected with used needles, prior alcohol treatment and depression. Although most HCV seropositive IDUs in our sample appear informed about their increased risk of liver disease from alcohol, two-fifths screened positive for problem alcohol use. These findings underscore the importance of referring HCV-positive persons to effective alcohol treatment programs to reduce future liver damage and improve eligibility for and effectiveness of treatment of HCV. PMID:16129567

  2. Interleukin-17 exacerbates hepatic steatosis and inflammation in non-alcoholic fatty liver disease

    PubMed Central

    Tang, Y; Bian, Z; Zhao, L; Liu, Y; Liang, S; Wang, Q; Han, X; Peng, Y; Chen, X; Shen, L; Qiu, D; Li, Z; Ma, X

    2011-01-01

    Mechanisms associated with the progression of simple steatosis to non-alcoholic fatty liver disease (NAFLD) remain undefined. Regulatory T cells (Tregs) play a critical role in regulating inflammatory processes in non-alcoholic steatohepatitis (NASH) and because T helper type 17 (Th17) functionally oppose Treg-mediated responses, this study focused on characterizing the role of Th17 cells using a NAFLD mouse model. C57BL/6 mice were fed either a normal diet (ND) or high fat (HF) diet for 8 weeks. Mice in the HF group had a significantly higher frequency of liver Th17 cells compared to ND-fed mice. Neutralization of interleukin (IL)-17 in HF mice ameliorated lipopolysaccharide (LPS)-induced liver injury reflected by decreased serum alanine aminotransferase (ALT) levels and reduced inflammatory cell infiltrates in the liver. In vitro, HepG2 cells cultured in the presence of free fatty acids (FFA; oleic acid and palmitic acid) for 24 h and IL-17 developed steatosis via insulin-signalling pathway interference. IL-17 and FFAs synergized to induce IL-6 production by HepG2 cells and murine primary hepatocytes which, in combination with transforming growth factor (TGF-β), expanded Th17 cells. It is likely that a similar process occurs in NASH patients, as there were significant levels of IL-17+ cell infiltrates in NASH patient livers. The hepatic expression of Th17 cell-related genes [retinoid-related orphan receptor gamma (ROR)γt, IL-17, IL-21 and IL-23] was also increased significantly in NASH patients compared to healthy controls. Th17 cells and IL-17 were associated with hepatic steatosis and proinflammatory response in NAFLD and facilitated the transition from simple steatosis to steatohepatitis. Strategies designed to alter the balance between Th17 cells and Tregs should be explored as a means of preventing progression to NASH and advanced liver diseases in NAFLD patients. PMID:21985374

  3. Recurrent hepatitis C and non-alcoholic fatty liver disease in transplanted patients: a review.

    PubMed

    Testino, G; Sumberaz, A; Leone, S; Borro, P

    2013-04-01

    Non-alcoholic fatty liver disease (NAFLD) is a common occurrence after orthotopic liver transplantation (OLT). The association steatosis/HCV determines important implications for clinical practice: steatosis accelerates the progression of fibrosis and reduces the likelihood of obtaining a sustained virological response (SVR) with antiviral therapy. In post-transplant HCV patients we have evidenced a strong correlation between body mass index (BMI), cholesterol, triglycerides (TGC) and hepatic percentage of steatosis. In subjects with BMI <25 and TGC <160 ng/mL, the chance of SVR was 48 times higher than that of non response. The chances of SVR and sustained biochemical response for patients with percentage of steatosis <15 were 12 times higher than that with higher percentage of steatosis. We can conclude how the amount of steatosis be noted specifically in biopsy examination reports of patients with relapse chronic hepatitis C and how the management of dismetabolism, diet and exercise therapy can improve BMI, liver histology and the response to antiviral therapy. PMID:23514999

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

    PubMed Central

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

    2015-01-01

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

  5. Increased hepatic receptor interacting protein kinase 3 expression due to impaired proteasomal functions contributes to alcohol-induced steatosis and liver injury

    PubMed Central

    Wang, Shaogui; Ni, Hong-Min; Dorko, Kenneth; Kumer, Sean C.; Schmitt, Timothy M.; Nawabi, Atta; Komatsu, Masaaki; Huang, Heqing; Ding, Wen-Xing

    2016-01-01

    Chronic alcohol exposure increased hepatic receptor-interacting protein kinase (RIP) 3 expression and necroptosis in the liver but its mechanisms are unclear. In the present study, we demonstrated that chronic alcohol feeding plus binge (Gao-binge) increased RIP3 but not RIP1 protein levels in mouse livers. RIP3 knockout mice had decreased serum alanine amino transferase activity and hepatic steatosis but had no effect on hepatic neutrophil infiltration compared with wild type mice after Gao-binge alcohol treatment. The hepatic mRNA levels of RIP3 did not change between Gao-binge and control mice, suggesting that alcohol-induced hepatic RIP3 proteins are regulated at the posttranslational level. We found that Gao-binge treatment decreased the levels of proteasome subunit alpha type-2 (PSMA2) and proteasome 26S subunit, ATPase 1 (PSMC1) and impaired hepatic proteasome function. Pharmacological or genetic inhibition of proteasome resulted in the accumulation of RIP3 in mouse livers. More importantly, human alcoholics had decreased expression of PSMA2 and PSMC1 but increased protein levels of RIP3 compared with healthy human livers. Moreover, pharmacological inhibition of RIP1 decreased Gao-binge-induced hepatic inflammation, neutrophil infiltration and NF-κB subunit (p65) nuclear translocation but failed to protect against steatosis and liver injury induced by Gao-binge alcohol. In conclusion, results from this study suggest that impaired hepatic proteasome function by alcohol exposure may contribute to hepatic accumulation of RIP3 resulting in necroptosis and steatosis while RIP1 kinase activity is important for alcohol-induced inflammation. PMID:26769846

  6. Effectiveness of exercise in hepatic fat mobilization in non-alcoholic fatty liver disease: Systematic review

    PubMed Central

    Golabi, Pegah; Locklear, Cameron T; Austin, Patrick; Afdhal, Sophie; Byrns, Melinda; Gerber, Lynn; Younossi, Zobair M

    2016-01-01

    AIM: To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease (NAFLD) patients. METHODS: Ovid-Medline, PubMed, EMBASE and Cochrane database were searched for randomized trials and prospective cohort studies in adults aged ≥ 18 which investigated the effects of at least 8 wk of exercise only or combination with diet on NAFLD from 2010 to 2016. The search terms used to identify articles, in which exercise was clearly described by type, duration, intensity and frequency were: “NASH”, “NAFLD”, “non-alcoholic steatohepatitis”, “non-alcoholic fatty liver disease”, “fat”, “steatosis”, “diet”, “exercise”, “MR spectroscopy” and “liver biopsy”. NAFLD diagnosis, as well as the outcome measures, was confirmed by either hydrogen-magnetic resonance spectroscopy (H-MRS) or biopsy. Trials that included dietary interventions along with exercise were accepted if they met all criteria. RESULTS: Eight studies met selection criteria (6 with exercise only, 2 with diet and exercise with a total of 433 adult participants). Training interventions ranged between 8 and 48 wk in duration with a prescribed exercise frequency of 3 to 7 d per week, at intensities between 45% and 75% of VO2 peak. The most commonly used imaging modality was H-MRS and one study utilized biopsy. The effect of intervention on fat mobilization was 30.2% in the exercise only group and 49.8% in diet and exercise group. There was no difference between aerobic and resistance exercise intervention, although only one study compared the two interventions. The beneficial effects of exercise on intrahepatic triglyceride (IHTG) were seen even in the absence of significant weight loss. Although combining an exercise program with dietary interventions augmented the reduction in IHTG, as well as improved measures of glucose control and/or insulin sensitivity, exercise only significantly decreased hepatic lipid contents

  7. Alcoholic hepatitis accelerates early hepatobiliary cancer by increasing stemness and miR-122-mediated HIF-1α activation

    PubMed Central

    Ambade, Aditya; Satishchandran, Abhishek; Szabo, Gyongyi

    2016-01-01

    Alcohol-related hepatocellular carcinoma (HCC) develops with advanced alcoholic liver disease and liver fibrosis. Using adult mice, we evaluate the effect of alcoholic steatohepatitis on early hepatobiliary carcinoma after initiation by diethyl-nitrosamine (DEN). Here we show that alcohol-fed DEN-injected mice have higher ALT and liver-to-body weight ratio compared to pair-fed DEN-injected mice. Alcohol feeding results in steatohepatitis indicated by increased pro-inflammatory cytokines and fibrotic genes. MRI and liver histology of alcohol+DEN mice shows hepatobiliary cysts, early hepatic neoplasia and increase in serum alpha-fetoprotein. Proliferation makers (BrdU, cyclin D1, p53) and cancer stem cell markers (CD133 and nanog) are significantly up-regulated in livers of alcohol-fed DEN-injected mice compared to controls. In livers with tumors, loss of miR-122 expression with a significant up-regulation of miR-122 target HIF-1α is seen. We conclude that alcoholic steatohepatitis accelerates hepatobiliary tumors with characteristic molecular features of HCC by up-regulating inflammation, cell proliferation, stemness, and miR-122 loss. PMID:26888602

  8. 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

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

    2009-09-01

    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

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

    PubMed

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

    2015-06-01

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

  10. Alcohol

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Alcohol KidsHealth > For Teens > Alcohol Print A A A ... you can make an educated choice. What Is Alcohol? Alcohol is created when grains, fruits, or vegetables ...

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

    PubMed

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

    2014-09-01

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

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

    PubMed Central

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

    2014-01-01

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

  13. Hepatitis

    MedlinePlus

    ... has been associated with drinking contaminated water. Hepatitis Viruses Type Transmission Prognosis A Fecal-oral (stool to ... risk for severe disease. Others A variety of viruses can affect the liver Signs and Symptoms Hepatitis ...

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

    PubMed Central

    2011-01-01

    Background Diabetes mellitus is associated with metabolic dysfunctions, including alterations in circulating lipid levels and fat tissue accumulation, which causes, among other pathologies, non-alcoholic fatty liver disease (NAFLD). Aim of the study The objective of this study was to analyse the effects of physical exercise and spirulina intake on the control of NAFLD in diabetic Wistar rats. Methods Diabetes was induced in the animals through intravenous administration of alloxan. The rats were divided into four groups: Diabetic Control (DC) - diabetic rats fed with a control diet and no physical exercise; Diabetic Spirulina (DS) - diabetic rats fed with a diet that included spirulina; Diabetic Spirulina and Exercise (DSE) - diabetic rats fed with a diet that included Spirulina and that exercised; and Diabetic Exercise (DE) - diabetic rats fed with a control diet and that exercised. Results The groups DS, DSE, and DE presented lower plasma concentrations of LDL cholesterol than DC, as well as lower levels of total liver lipids in groups DS, DSE, and DE in comparison to DC. Conclusion Thus, spirulina appears to be effective in reducing total circulating levels of LDL-cholesterol and hepatic lipids, alone or in conjunction with physical exercise in diabetic rats. PMID:21569626

  15. Dietary α-linolenic acid-rich flaxseed oil prevents against alcoholic hepatic steatosis via ameliorating lipid homeostasis at adipose tissue-liver axis in mice

    PubMed Central

    Wang, Meng; Zhang, Xiao-Jing; Feng, Kun; He, Chengwei; Li, Peng; Hu, Yuan-Jia; Su, Huanxing; Wan, Jian-Bo

    2016-01-01

    Low levels of n-3 polyunsaturated fatty acids (PUFAs) in serum and liver tissue biopsies are the common characteristics in patients with alcoholic liver disease. The α-linolenic acid (ALA) is a plant-derived n-3 PUFA and is rich in flaxseed oil. However, the impact of ALA on alcoholic fatty liver is largely unknown. In this study, we assessed the potential protective effects of ALA-rich flaxseed oil (FO) on ethanol-induced hepatic steatosis and observed that dietary FO supplementation effectively attenuated the ethanol-induced hepatic lipid accumulation in mice. Ethanol exposure stimulated adipose lipolysis but reduced fatty acid/lipid uptake, which were normalized by FO. Our investigations into the corresponding mechanisms demonstrated that the ameliorating effect of FO might be associated with the lower endoplasmic reticulum stress and normalized lipid metabolism in adipose tissue. In the liver, alcohol exposure stimulated hepatic fatty acid uptake and triglyceride synthesis, which were attenuated by FO. Additionally, dietary FO upregulated plasma adiponectin concentration, hepatic adiponectin receptor 2 expression, and the activation of hepatic adenosine monophosphate-activated protein kinase. Collectively, dietary FO protects against alcoholic hepatic steatosis by improving lipid homeostasis at the adipose tissue-liver axis, suggesting that dietary ALA-rich flaxseed oil might be a promising approach for prevention of alcoholic fatty liver. PMID:27220557

  16. 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 ...

  17. 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 ...

  18. Bone marrow stem cells contribute to alcohol liver fibrosis in humans.

    PubMed

    Dalakas, Evangelos; Newsome, Philip N; Boyle, Shelagh; Brown, Rachael; Pryde, Anne; McCall, Shonna; Hayes, Peter C; Bickmore, Wendy A; Harrison, David J; Plevris, John N

    2010-09-01

    Bone marrow-derived stem cell (BMSC) contribution to liver repair varies considerably and recent evidence suggests these cells may contribute to liver fibrosis. We investigated the mobilization and hepatic recruitment of bone marrow (BM) stem cells in patients with alcohol liver injury and their contribution to parenchymal/non-parenchymal liver cell lineages. Liver biopsies from alcoholic hepatitis (AH) patients and male patients, who received a female liver transplant and developed AH, were analyzed for BM stem cell content by fluorescence in situ hybridization and immunostaining. Y chromosome analysis was performed, along with co-staining for hepatocyte, biliary, myofibroblast, and Ki-67 markers. Blood CD34(+) levels were quantified in AH patients by flow cytometry. AH patients had increased CD34(+) cell counts in liver tissue (1.834% +/- 0.605%; P < 0.05) and in blood (0.195% +/- 0.063%; P < 0.05) as compared with matched controls (0.299% + 0.208% and 0.067% +/- 0.01%). A proportion of hepatic myofibroblasts were BM-derived (7.9%-26.8%) as deemed by the co-localization of Y chromosome/alpha-smooth muscle actin (alpha-SMA) staining. In the cross-sex liver grafts with AH, 5.025% of the myofibroblasts were co-staining for CD34, suggesting that a population of CD34(+) cells were contributing to the hepatic myofibroblast population. There was no evidence of BM contribution to hepatocyte or biliary cell differentiation, nor evidence of increased hepatocyte regeneration. Alcohol liver injury mobilizes CD34(+) stem cells into the circulation and recruits them into the liver. These BMSCs contribute to the hepatic myofibroblast population but not to parenchymal lineages and do not promote hepatocyte repair.

  19. Autoimmune Hepatitis Induced by Syngeneic Liver Cytosolic Proteins Biotransformed by Alcohol Metabolites

    PubMed Central

    Thiele, Geoffrey M.; Duryee, Michael J.; Willis, Monte S.; Tuma, Dean J.; Radio, Stanley J.; Hunter, Carlos D.; Schaffert, Courtney S.; Klassen, Lynell W.

    2010-01-01

    Background & Aims Aldehydes that are produced following the breakdown of ethanol (acetaldehyde) and lipid peroxidation of membranes (malondialdehyde) have been shown to bind (adduct) proteins. Additionally, these two aldehydes can combine (MAA) on non-syngeneic and syngeneic proteins to initiate numerous immune responses to the unmodified part of the protein in the absence of an adjuvant. Therefore, these studies provide a potential mechanism for the development of antigen-specific immune responses resulting in liver damage should syngeneic liver proteins be adducted with MAA. Methods This study sought to test whether MAA modified syngeneic liver cytosolic proteins administered daily in the absence of adjuvant into C57BL/6 mice abrogates tolerance to initiate a MAA induced autoimmune-like hepatitis (MIAH). Results In mice immunized with MAA modified cytosols there was an increase in liver damage as assessed by AST/ALT levels that correlated with liver pathology scores and the presence of the pro-fibrotic factors; smooth muscle actin (SMA), TGF-β, and collagen. IgG antibodies and T-cell proliferative responses specific for cytosolic proteins were also detected. Pro-inflammatory cytokines were produced in the livers of animals exposed to MAA-modified cytosols. Finally, transfer of immunized T-cells to naïve animals caused biochemical and histological evidence of liver damage. Conclusions These data demonstrate that a disease with an autoimmune-like pathophysiology can be generated in this animal model using soluble MAA modified syngeneic liver cytosols as the immunogen. These studies provide insight into potential mechanism(s) that the metabolites of alcohol may play in contributing to the onset of an autoimmune-like disease in ALD patients. PMID:20860619

  20. Alcohol

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Alcohol KidsHealth > For Kids > Alcohol Print A A A Text Size What's in ... What Is Alcoholism? Say No en español El alcohol Getting the Right Message "Hey, who wants a ...

  1. Helenalin attenuates alcohol-induced hepatic fibrosis by enhancing ethanol metabolism, inhibiting oxidative stress and suppressing HSC activation.

    PubMed

    Lin, Xing; Zhang, Shijun; Huang, Renbin; Wei, Ling; Tan, Shimei; Liang, Shuang; Tian, Yuanchun; Wu, Xiaoyan; Lu, Zhongpeng; Huang, Quanfang

    2014-06-01

    A compound was isolated from Centipeda minima using bioassay-guided screening. The structure of this compound was elucidated based on its spectral data, and it was identified as helenalin. The hepatoprotective effect of helenalin was evaluated using a liver fibrosis model induced by intragastric administration with alcohol within 24 weeks in rats. The results revealed that helenalin significantly prevented alcohol-induced hepatic injury and fibrogenesis, as evidenced by the decrease in serum aminotransferase, the attenuation of histopathological changes, and the inhibition of the hepatic fibrosis indicators, such as hyaluronic acid, type III precollagen, laminin, hydroxyproline and collagen α type I. Mechanistically, studies showed that helenalin expedited ethanol metabolism by enhancing the alcohol and aldehyde dehydrogenase activities. Furthermore, helenalin alleviated lipid peroxidation, recruited the antioxidative defense system, inhibited CYP2E1 activity, and reduced the inflammatory mediators, including TGF-β1, TNF-α, IL-6 and IL-1β and myeloperoxidase, via down-regulation of NF-κB. Helenalin significantly decreased collagen deposition by reducing the profibrotic cytokines like transforming growth factor-β, platelet-derived growth factor-β and connective tissue growth factor, and promoted extracellular matrix degradation by modulating the levels of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-9. In addition, helenalin inhibited HSC activation as evidenced by the down-regulation of α-SMA and TGF-β levels. In conclusion, helenalin had a significant protective effect on chronic ethanol-induced hepatic fibrosis and may be a major bioactive ingredient of C. minima.

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

    PubMed

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

    2013-12-01

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

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

    PubMed Central

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

    2013-01-01

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

  4. Systematic transcriptome analysis reveals elevated expression of alcohol-metabolizing genes in NAFLD livers.

    PubMed

    Zhu, Ruixin; Baker, Susan S; Moylan, Cynthia A; Abdelmalek, Manal F; Guy, Cynthia D; Zamboni, Fausto; Wu, Dingfeng; Lin, Weili; Liu, Wensheng; Baker, Robert D; Govindarajan, Sugantha; Cao, Zhiwei; Farci, Patrizia; Diehl, Anna Mae; Zhu, Lixin

    2016-03-01

    Obese animals and non-alcoholic fatty liver disease (NAFLD) patients exhibit elevated blood alcohol, suggesting potential contributions of alcohol metabolism to the development of NAFLD. Liver gene expression in patients with biopsy-proven mild (N = 40) and severe (N = 32) NAFLD were compared to that in healthy liver donors (N = 7) and alcoholic hepatitis (AH; N = 15) using microarrays. Principal components analyses (PCA) revealed similar gene expression patterns between mild and severe NAFLD which clustered with those of AH but were distinct from those of healthy livers. Differential gene expression between NAFLD and healthy livers was consistent with established NAFLD-associated genes and NAFLD pathophysiology. Alcohol-metabolizing enzymes including ADH, ALDH, CYP2E1, and CAT were up-regulated in NAFLD livers. The expression level of alcohol-metabolizing genes in severe NAFLD was similar to that in AH. The NAFLD gene expression profiles provide new directions for future investigations to identify disease markers and targets for prevention and treatment, as well as to foster our understanding of NAFLD pathogenesis and pathophysiology. Particularly, increased expression of alcohol-metabolizing genes in NAFLD livers supports a role for endogenous alcohol metabolism in NAFLD pathology and provides further support for gut microbiome therapy in NAFLD management. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley © Sons, Ltd.

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

    PubMed

    Summa, Keith C; Voigt, Robin M; Forsyth, Christopher B; Shaikh, Maliha; Cavanaugh, Kate; Tang, Yueming; Vitaterna, Martha Hotz; Song, Shiwen; Turek, Fred W; Keshavarzian, Ali

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  7. Alcoholism

    PubMed Central

    Girard, Donald E.; Carlton, Bruce E.

    1978-01-01

    There are important measurements of alcoholism that are poorly understood by physicians. Professional attitudes toward alcoholic patients are often counterproductive. Americans spend about $30 billion on alcohol a year and most adults drink alcohol. Even though traditional criteria allow for recognition of the disease, diagnosis is often made late in the natural course, when intervention fails. Alcoholism is a major health problem and accounts for 10 percent of total health care costs. Still, this country's 10 million adult alcoholics come from a pool of heavy drinkers with well defined demographic characteristics. These social, cultural and familial traits, along with subtle signs of addiction, allow for earlier diagnosis. Although these factors alone do not establish a diagnosis of alcoholism, they should alert a physician that significant disease may be imminent. Focus must be directed to these aspects of alcoholism if containment of the problem is expected. PMID:685264

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

    PubMed Central

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

    2014-01-01

    In the current study, the therapeutic effects of zeaxanthin dipalmitate (ZD) on a rat alcoholic fatty liver disease (AFLD) model were evaluated. After-treatment with ZD from the 5th week to the 10th week in a 10-week ethanol intragastric administration in rats significantly alleviated the typical AFLD symptoms, including reduction in rat body weight, accumulation of hepatic fat droplets, occurrence of oxidative stress, inflammation, chemoattractive responses and hepatic apoptosis in the liver. The reduction of liver function abnormalities by ZD was partly through lower expression level of cytochrome P450 2E1 (CYP2E1), diminished activity of nuclear factor kappa B (NF-κB) through the restoration of its inhibitor kappa B alpha (IκBα), 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

  9. Alcohol and Cirrhosis

    MedlinePlus

    ... that a non-drinker with hepatitis C has. Alcohol and hepatitis C both damage the liver, so together, the risk of serious liver damage (cirrhosis) is much higher than with either alone. < Previous Living with Hepatitis ...

  10. Liver biochemistry and associations with alcohol intake, hepatitis B virus infection and Inuit ethnicity: a population-based comparative epidemiological survey in Greenland and Denmark

    PubMed Central

    Rex, Karsten Fleischer; Krarup, Henrik Bygum; Laurberg, Peter; Andersen, Stig

    2016-01-01

    Background Hepatitis B virus (HBV) infection is common in Arctic populations and high alcohol intake has been associated with an increased risk of a number of diseases. Yet, a description of the influence of alcohol intake in persons with HBV infection on liver biochemistry is lacking. Objective We aimed to describe the association between reported alcohol intake and liver biochemistry taking into account also HBV infection, ethnicity, Inuit diet, body mass index (BMI), gender and age in an Arctic population. Design and methods Population-based investigation of Inuit (n=441) and non-Inuit (94) in Greenland and Inuit living in Denmark (n=136). Participants filled in a questionnaire on alcohol intake and other life style factors. Blood samples were tested for aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), bilirubin, albumin, hepatitis B surface antigen, hepatitis B surface antibody and hepatitis B core antibody. We also performed physical examinations. Results Participation rate was 95% in Greenland and 52% in Denmark. An alcohol intake above the recommended level was reported by 12.9% of non-Inuit in Greenland, 9.1% of Inuit in East Greenland, 6.1% of Inuit migrants and 3.4% of Inuit in the capital of Greenland (p=0.035). Alcohol intake was associated with AST (p<0.001) and GGT (p=0.001), and HBV infection was associated with ALP (p=0.001) but not with AST, GGT, bilirubin or albumin in the adjusted analysis. Inuit had higher AST (p<0.001), GGT (p<0.001) and ALP (p=0.001) values than non-Inuit after adjustment for alcohol, diet, BMI and HBV exposure. Ethnic origin modified the association between alcohol and AST, while HBV infection did not modify the associations between alcohol and liver biochemistry. Conclusions Non-Inuit in Greenland reported a higher alcohol intake than Inuit. Ethnic origin was more markedly associated with liver biochemistry than was alcohol intake, and Greenlandic ethnicity modified the effect

  11. Dietary tomato powder inhibits alcohol-induced hepatic injury by suppressing cytochrome p450 2E1 induction in rodent models.

    PubMed

    Stice, Camilla P; Liu, Chun; Aizawa, Koichi; Greenberg, Andrew S; Ausman, Lynne M; Wang, Xiang-Dong

    2015-04-15

    Chronic and excessive alcohol consumption leads to the development of alcoholic liver disease (ALD) and greatly increases the risk of liver cancer. Induction of the cytochrome p450 2E1 (CYP2E1) enzyme by chronic and excessive alcohol intake is known to play a role in the pathogenesis of ALD. High intake of tomatoes, rich in the carotenoid lycopene, is associated with a decreased risk of chronic disease. We investigated the effects of whole tomato (tomato powder, TP), partial tomato (tomato extract, TE), and purified lycopene (LYC) against ALD development in rats. Of the three supplements, only TP reduced the severity of alcohol-induced steatosis, hepatic inflammatory foci, and CYP2E1 protein levels. TE had no effect on these outcomes and LYC greatly increased inflammatory foci in alcohol-fed rats. To further support the protective effect of TP against ALD, TP was supplemented in a carcinogen (diethylnitrosamine, DEN)-initiated alcohol-promoted mouse model. In addition to reduced steatosis and inflammatory foci, TP abolished the presence of preneoplastic foci of altered hepatocytes in DEN-injected mice fed alcohol. These reductions were associated with decreased hepatic CYP2E1 protein levels, restored levels of peroxisome proliferator-activated receptor-α and downstream gene expression, decreased inflammatory gene expression, and reduced endoplasmic reticulum stress markers. These data provide strong evidence for TP as an effective whole food prevention strategy against ALD.

  12. Dietary tomato powder inhibits alcohol-induced hepatic injury by suppressing cytochrome p450 2E1 induction in rodent models

    PubMed Central

    Stice, Camilla P.; Liu, Chun; Aizawa, Koichi; Greenberg, Andrew S.; Ausman, Lynne M.; Wang, Xiang-Dong

    2015-01-01

    Chronic and excessive alcohol consumption leads to the development of alcoholic liver disease (ALD) and greatly increases the risk of liver cancer. Induction of the cytochrome p450 2E1 (CYP2E1) enzyme by chronic and excessive alcohol intake is known to play a role in the pathogenesis of ALD. High intake of tomatoes, rich in the carotenoid lycopene, is associated with a decreased risk of chronic disease. We investigated the effects of whole tomato (tomato powder, TP), partial tomato (tomato extract, TE), and purified lycopene (LYC) against ALD development in rats. Of the three supplements, only TP reduced the severity of alcohol-induced steatosis, hepatic inflammatory foci, and CYP2E1 protein levels. TE had no effect on these outcomes and LYC greatly increased inflammatory foci in alcohol-fed rats. To further support the protective effect of TP against ALD, TP was supplemented in a carcinogen (diethylnitrosamine, DEN)-initiated alcohol-promoted mouse model. In addition to reduced steatosis and inflammatory foci, TP abolished the presence of preneoplastic foci of altered hepatocytes in DEN-injected mice fed alcohol. These reductions were associated with decreased hepatic CYP2E1 protein levels, restored levels of peroxisome proliferator-activated receptor-α and downstream gene expression, decreased inflammatory gene expression, and reduced endoplasmic reticulum stress markers. These data provide strong evidence for TP as an effective whole food prevention strategy against ALD. PMID:25592162

  13. Dietary tomato powder inhibits alcohol-induced hepatic injury by suppressing cytochrome p450 2E1 induction in rodent models.

    PubMed

    Stice, Camilla P; Liu, Chun; Aizawa, Koichi; Greenberg, Andrew S; Ausman, Lynne M; Wang, Xiang-Dong

    2015-04-15

    Chronic and excessive alcohol consumption leads to the development of alcoholic liver disease (ALD) and greatly increases the risk of liver cancer. Induction of the cytochrome p450 2E1 (CYP2E1) enzyme by chronic and excessive alcohol intake is known to play a role in the pathogenesis of ALD. High intake of tomatoes, rich in the carotenoid lycopene, is associated with a decreased risk of chronic disease. We investigated the effects of whole tomato (tomato powder, TP), partial tomato (tomato extract, TE), and purified lycopene (LYC) against ALD development in rats. Of the three supplements, only TP reduced the severity of alcohol-induced steatosis, hepatic inflammatory foci, and CYP2E1 protein levels. TE had no effect on these outcomes and LYC greatly increased inflammatory foci in alcohol-fed rats. To further support the protective effect of TP against ALD, TP was supplemented in a carcinogen (diethylnitrosamine, DEN)-initiated alcohol-promoted mouse model. In addition to reduced steatosis and inflammatory foci, TP abolished the presence of preneoplastic foci of altered hepatocytes in DEN-injected mice fed alcohol. These reductions were associated with decreased hepatic CYP2E1 protein levels, restored levels of peroxisome proliferator-activated receptor-α and downstream gene expression, decreased inflammatory gene expression, and reduced endoplasmic reticulum stress markers. These data provide strong evidence for TP as an effective whole food prevention strategy against ALD. PMID:25592162

  14. AH Her Observing Campaign

    NASA Astrophysics Data System (ADS)

    Waagen, Elizabeth O.

    2013-05-01

    Dr. Juan Echevarria (Universidad Nacional Autónoma de México) and colleagues request AAVSO assistance in a campaign on the Z Cam-type cataclysmic variable AH Her being carried out 2013 May 29 - June 18. They will be making photometric and spectroscopic observations of AH Her using the 2.1m and 0.84m telescopes at San Pedro Martir Observatory (SPM). Their goal is to carry out a radial velocity study of the system components using modern detectors; no study of AH Her has been made since the one by Horne, Wade, and Szkody in 1980-1981 (1986MNRAS.219..791H). Photometry and spectroscopy are requested. AH Her, for decades a reasonably "regular" Z Cam system, began exhibiting significantly anomalous behavior in ~2007. Since then it has experienced brief periods of fairly typical behavior interspersed with more anomalous intervals, including some unprecedented behavior. Most recently, it has returned to a more normal pattern of outbursts shape-wise but it is not back to its normal amplitude or frequency. AAVSO data will be essential for correlation in order to determine the precise time(s) of minimum occurring during the campaign. Finder charts with sequences may be created using the AAVSO Variable Star Plotter (http://www.aavso.org/vsp). Observations should be submitted to the AAVSO International Database. See full Alert Notice for more details.

  15. Altered hepatic lipid metabolism in C57BL/6 mice fed alcohol: a targeted lipidomic and gene expression study[S

    PubMed Central

    Clugston, Robin D.; Jiang, Hongfeng; Lee, Man Xia; Piantedosi, Roseann; Yuen, Jason J.; Ramakrishnan, Rajasekhar; Lewis, Michael J.; Gottesman, Max E.; Huang, Li-Shin; Goldberg, Ira J.; Berk, Paul D.; Blaner, William S.

    2011-01-01

    Chronic alcohol consumption is associated with fatty liver disease in mammals. The object of this study was to gain an understanding of dysregulated lipid metabolism in alcohol-fed C57BL/6 mice using a targeted lipidomic approach. Liquid chromatography tandem mass spectrometry was used to analyze several lipid classes, including free fatty acids, fatty acyl-CoAs, fatty acid ethyl esters, sphingolipids, ceramides, and endocannabinoids, in plasma and liver samples from control and alcohol-fed mice. The interpretation of lipidomic data was augmented by gene expression analyses for important metabolic enzymes in the lipid pathways studied. Alcohol feeding was associated with i) increased hepatic free fatty acid levels and decreased fatty acyl-CoA levels associated with decreased mitochondrial fatty acid oxidation and decreased fatty acyl-CoA synthesis, respectively; ii) increased hepatic ceramide levels associated with higher levels of the precursor molecules sphingosine and sphinganine; and iii) increased hepatic levels of the endocannabinoid anandamide associated with decreased expression of its catabolic enzyme fatty acid amide hydrolase. The unique combination of lipidomic and gene expression analyses allows for a better mechanistic understanding of dysregulated lipid metabolism in the development of alcoholic fatty liver disease. PMID:21856784

  16. Purple potato (Solanum tuberosum L.) anthocyanins attenuate alcohol-induced hepatic injury by enhancing antioxidant defense.

    PubMed

    Jiang, Zhihui; Chen, Chen; Wang, Jian; Xie, Wenyan; Wang, Meng; Li, Xinsheng; Zhang, Xiaoying

    2016-01-01

    Alcoholic liver disease (ALD) is a serious and challenging health issue. In the past decade, natural components possessing hepatoprotective properties have gained more attention for ALD intervention. In this study, the phytochemical components of anthocyanins from purple potato were assessed using UPLC-MS/MS, and the hepatoprotective effects of purple potato anthocyanins (PPAs) were investigated in the ALD mouse model. Serum and liver biochemical parameters were determined, along with histopathological changes in liver tissue. In addition, the major contributors to alcohol-induced oxidative stress were assessed. The results indicated that the levels of aspartate transaminase and alanine transaminase were lower in the serum of the PPA-treated group than the alcohol-treated group. PPAs significantly inhibited the reduction of total cholesterol and triglycerides. Higher levels of superoxide dismutase and reduced glutathione enzymes as well as a reduction in the formation of malondialdehyde occurred in mice fed with PPAs. In addition, PPAs protected against increased alcohol-induced levels and activity of cytochrome P450 2E1 (CYP2E1), which demonstrates the effects of PPAs against alcohol-induced oxidative stress and liver injury. This study suggests that PPAs could be an effective therapeutic agent in alcohol-induced liver injuries by inhibiting CYP2E1 expression and thereby strengthening antioxidant defenses. PMID:26481011

  17. Purple potato (Solanum tuberosum L.) anthocyanins attenuate alcohol-induced hepatic injury by enhancing antioxidant defense.

    PubMed

    Jiang, Zhihui; Chen, Chen; Wang, Jian; Xie, Wenyan; Wang, Meng; Li, Xinsheng; Zhang, Xiaoying

    2016-01-01

    Alcoholic liver disease (ALD) is a serious and challenging health issue. In the past decade, natural components possessing hepatoprotective properties have gained more attention for ALD intervention. In this study, the phytochemical components of anthocyanins from purple potato were assessed using UPLC-MS/MS, and the hepatoprotective effects of purple potato anthocyanins (PPAs) were investigated in the ALD mouse model. Serum and liver biochemical parameters were determined, along with histopathological changes in liver tissue. In addition, the major contributors to alcohol-induced oxidative stress were assessed. The results indicated that the levels of aspartate transaminase and alanine transaminase were lower in the serum of the PPA-treated group than the alcohol-treated group. PPAs significantly inhibited the reduction of total cholesterol and triglycerides. Higher levels of superoxide dismutase and reduced glutathione enzymes as well as a reduction in the formation of malondialdehyde occurred in mice fed with PPAs. In addition, PPAs protected against increased alcohol-induced levels and activity of cytochrome P450 2E1 (CYP2E1), which demonstrates the effects of PPAs against alcohol-induced oxidative stress and liver injury. This study suggests that PPAs could be an effective therapeutic agent in alcohol-induced liver injuries by inhibiting CYP2E1 expression and thereby strengthening antioxidant defenses.

  18. Assessment of Portal Venous and Hepatic Artery Haemodynamic Variation in Non-Alcoholic Fatty Liver Disease (NAFLD) Patients

    PubMed Central

    Balasubramanian, Padhmini; Govindasamy, Ezhumalai; Venkatesh, Basavaiya Prabhu

    2016-01-01

    Introduction Non-Alcoholic Fatty Liver Disease (NAFLD) has various spectrums of liver diseases like isolated fatty liver, steatohepatitis and cirrhosis usually progressing in a linear fashion. In this process they are known to cause certain haemodynamic changes in the portal flow and hepatic artery flow. Aim The aim of the study was to study these haemodynamic changes in patients with NAFLD and to correlate it with the disease severity. Materials and Methods Ninety patients diagnosed to have NAFLD based on ultrasound abdomen (30 each in grade1, grade2 and grade3 NAFLD) and 30 controls (Normal liver on ultrasound abdomen) were subjected to portal vein and hepatic artery Doppler study. Peak maximum velocity (Vmax), Peak minimum velocity (Vmin), Mean flow velocity (MFV), and Vein pulsality index (VPI) of the portal vein and hepatic artery resistivity index (HARI) of the hepatic artery were the doppler parameters which were assessed. Liver span was also assessed both for the fatty liver and controls. Results The mean Vmax, Vmin, MFV and VPI of the portal vein in patients with NAFLD was 12.23±1.74cm/sec, 9.31±1.45cm/sec, 10.76±1.48cm/sec, and 0.24±0.04 as compared to 14.05±2.43cm/sec, 10.01±2.27cm/sec, 12.23±2.47cm/sec, 0.3±0.08 in controls respectively. All these differences were statistically significant except for Vmin. The Mean HARI in patients with fatty liver was 0.65±0.06 when compared to controls of 0.75±0.06 (p=0.001). HARI (r-value of -0.517) had a better negative correlation followed by VPI (r-value of -0.44) and Vmax (r-value of -0.293) with the severity of NAFLD. MFV had a very weak negative correlation (r-value of -0.182) with the severity of NAFLD. Conclusion The Vmax, MFV, VPI and HARI were significantly less when compared to controls suggesting a reduced portal flow and an increased hepatic arterial flow in patients with NAFLD. Among the parameters, HARI correlated better with the severity of NAFLD followed by VPI. PMID:27656524

  19. Hepatitis

    MedlinePlus

    ... Fitness Diseases & Conditions Infections Q&A School & Jobs Drugs & Alcohol Staying Safe Recipes En Español Making a Change – Your Personal Plan Hot Topics Meningitis Choosing Your Mood Prescription Drug Abuse Healthy School Lunch Planner How Can I ...

  20. Hepatitis B

    MedlinePlus

    ... and Change Plan Wallet card for patients to record their alcohol use over a 4-week period as a way to monitor and reduce their drinking behavior. Glossary Definitions of terms commonly used with viral hepatitis and ...

  1. Alcohol.

    ERIC Educational Resources Information Center

    Schibeci, Renato

    1996-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  3. Transgenic Overexpression of Aryl Hydrocarbon Receptor Repressor (AhRR) and AhR-Mediated Induction of CYP1A1, Cytokines, and Acute Toxicity

    PubMed Central

    Vogel, Christoph F.A.; Chang, W.L. William; Kado, Sarah; McCulloh, Kelly; Vogel, Helena; Wu, Dalei; Haarmann-Stemmann, Thomas; Yang, GuoXiang; Leung, Patrick S.C.; Matsumura, Fumio; Gershwin, M. Eric

    2016-01-01

    Background: The aryl hydrocarbon receptor repressor (AhRR) is known to repress aryl hydrocarbon receptor (AhR) signaling, but very little is known regarding the role of the AhRR in vivo. Objective: This study tested the role of AhRR in vivo in AhRR overexpressing mice on molecular and toxic end points mediated through a prototypical AhR ligand. Methods: We generated AhRR-transgenic mice (AhRR Tg) based on the genetic background of C57BL/6J wild type (wt) mice. We tested the effect of the prototypical AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the expression of cytochrome P450 (CYP)1A1 and cytokines in various tissues of mice. We next analyzed the infiltration of immune cells in adipose tissue of mice after treatment with TCDD using flow cytometry. Results: AhRR Tg mice express significantly higher levels of AhRR compared to wt mice. Activation of AhR by TCDD caused a significant increase of the inflammatory cytokines Interleukin (IL)-1β, IL-6 and IL-10, and CXCL chemokines in white epididymal adipose tissue from both wt and AhRR Tg mice. However, the expression of IL-1β, CXCL2 and CXCL3 were significantly lower in AhRR Tg versus wt mice following TCDD treatment. Exposure to TCDD caused a rapid accumulation of neutrophils and macrophages in white adipose tissue of wt and AhRR Tg mice. Furthermore we found that male AhRR Tg mice were protected from high-dose TCDD-induced lethality associated with a reduced inflammatory response and liver damage as indicated by lower levels of TCDD-induced alanine aminotransferase and hepatic triglycerides. Females from both wt and AhRR Tg mice were less sensitive than male mice to acute toxicity induced by TCDD. Conclusion: In conclusion, the current study identifies AhRR as a previously uncharacterized regulator of specific inflammatory cytokines, which may protect from acute toxicity induced by TCDD. Citation: Vogel CF, Chang WL, Kado S, McCulloh K, Vogel H, Wu D, Haarmann-Stemmann T, Yang GX, Leung PS, Matsumura F

  4. Effects of artificial sweeteners on the AhR- and GR-dependent CYP1A1 expression in primary human hepatocytes and human cancer cells.

    PubMed

    Kamenickova, Alzbeta; Pecova, Michaela; Bachleda, Petr; Dvorak, Zdenek

    2013-12-01

    Food constituents may cause a phenomenon of food-drug interactions. In the current study, we examined the effects of artificial sweeteners (aspartame, acesulfame, cyclamate, saccharin) on the aryl hydrocarbon receptor (AhR) and glucocorticoid receptor (GR)-dependent expression of CYP1A1 in human hepatocytes, hepatic HepG2 and intestinal LS174T cancer cell lines. Sweeteners were tested in concentrations up to those occurring in non-alcoholic beverages. Basal and ligand-inducible AhR- and GR-dependent reporter gene activation in stably transfected HepG2 and HeLa cells, respectively, were not affected by either of the sweeteners tested after 24h of incubation. The expression of CYP1A1 mRNA and protein in primary cultures of human hepatocytes and in LS174T and HepG2 cells was not induced by any of the tested sweeteners. Overall, aspartame, acesulfame, saccharin and cyclamate had no effects on CYP1A1 expression and transcriptional activities of AhR and GR. These data imply the safety of artificial sweeteners in terms of interference with AhR, GR and CYP1A1.

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

    SciTech Connect

    Lin, R.C.; Miller, B.M. V.A. Medical Center, Indianapolis, IN )

    1991-03-11

    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.

  6. Murine Models of Acute Alcoholic Hepatitis and Their Relevance to Human Disease.

    PubMed

    Wilkin, Richard J W; Lalor, Patricia F; Parker, Richard; Newsome, Philip N

    2016-04-01

    Alcohol-induced liver damage is a major burden for most societies, and murine studies can provide a means to better understand its pathogenesis and test new therapies. However, there are many models reported with widely differing phenotypes, not all of which fully regenerate the spectrum of human disease. Thus, it is important to understand the implications of these variations to efficiently model human disease. This review critically appraises key articles in the field, detailing the spectrum of liver damage seen in different models, and how they relate to the phenotype of disease seen in patients. A range of different methods of alcohol administration have been studied, ranging from ad libitum consumption of alcohol and water to modified diets (eg, Lieber deCarli liquid diet). Other feeding regimens have taken more invasive routes using intragastric feeding tubes to infuse alcohol directly into the stomach. Notably, models using wild-type mice generally produce a milder phenotype of liver damage than those using genetically modified mice, with the exception of the chronic binge-feeding model. We recommend panels of tests for consideration to standardize end points for the evaluation of the severity of liver damage-key for comparison of models of injury, testing of new therapies, and subsequent translation of findings into clinical practice. PMID:26835538

  7. Deletion of tumor progression locus 2 attenuates alcohol induced hepatic inflammation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BACKGROUND: The pathogenesis of alcoholic liver disease (ALD) involves the interaction of several inflammatory signaling pathways. Tumor progression locus 2 (TPL2), also known as Cancer Osaka Thyroid (COT) and MAP3K8, is a serine threonine kinase that functions as a critical regulator of inflammator...

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

    SciTech Connect

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

    1981-02-01

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

  9. Lactobacillus rhamnosus GG supernatant promotes intestinal barrier function, balances Treg and TH17 cells and ameliorates hepatic injury in a mouse model of chronic-binge alcohol feeding.

    PubMed

    Chen, Rui-Cong; Xu, Lan-Man; Du, Shan-Jie; Huang, Si-Si; Wu, He; Dong, Jia-Jia; Huang, Jian-Rong; Wang, Xiao-Dong; Feng, Wen-Ke; Chen, Yong-Ping

    2016-01-22

    Impaired intestinal barrier function plays a critical role in alcohol-induced hepatic injury, and the subsequent excessive absorbed endotoxin and bacterial translocation activate the immune response that aggravates the liver injury. Lactobacillus rhamnosus GG supernatant (LGG-s) has been suggested to improve intestinal barrier function and alleviate the liver injury induced by chronic and binge alcohol consumption, but the underlying mechanisms are still not clear. In this study, chronic-binge alcohol fed model was used to determine the effects of LGG-s on the prevention of alcoholic liver disease in C57BL/6 mice and investigate underlying mechanisms. Mice were fed Lieber-DeCarli diet containing 5% alcohol for 10 days, and one dose of alcohol was gavaged on Day 11. In one group, LGG-s was supplemented along with alcohol. Control mice were fed isocaloric diet. Nine hours later the mice were sacrificed for analysis. Chronic-binge alcohol exposure induced an elevation in liver enzymes, steatosis and morphology changes, while LGG-s supplementation attenuated these changes. Treatment with LGG-s significantly improved intestinal barrier function reflected by increased mRNA expression of tight junction (TJ) proteins and villus-crypt histology in ileum, and decreased Escherichia coli (E. coli) protein level in liver. Importantly, flow cytometry analysis showed that alcohol reduced Treg cell population while increased TH17 cell population as well as IL-17 secretion, which was reversed by LGG-s administration. In conclusion, our findings indicate that LGG-s is effective in preventing chronic-binge alcohol exposure-induced liver injury and shed a light on the importance of the balance of Treg and TH17 cells in the role of LGG-s application.

  10. Lactobacillus rhamnosus GG supernatant promotes intestinal barrier function, balances Treg and TH17 cells and ameliorates hepatic injury in a mouse model of chronic-binge alcohol feeding.

    PubMed

    Chen, Rui-Cong; Xu, Lan-Man; Du, Shan-Jie; Huang, Si-Si; Wu, He; Dong, Jia-Jia; Huang, Jian-Rong; Wang, Xiao-Dong; Feng, Wen-Ke; Chen, Yong-Ping

    2016-01-22

    Impaired intestinal barrier function plays a critical role in alcohol-induced hepatic injury, and the subsequent excessive absorbed endotoxin and bacterial translocation activate the immune response that aggravates the liver injury. Lactobacillus rhamnosus GG supernatant (LGG-s) has been suggested to improve intestinal barrier function and alleviate the liver injury induced by chronic and binge alcohol consumption, but the underlying mechanisms are still not clear. In this study, chronic-binge alcohol fed model was used to determine the effects of LGG-s on the prevention of alcoholic liver disease in C57BL/6 mice and investigate underlying mechanisms. Mice were fed Lieber-DeCarli diet containing 5% alcohol for 10 days, and one dose of alcohol was gavaged on Day 11. In one group, LGG-s was supplemented along with alcohol. Control mice were fed isocaloric diet. Nine hours later the mice were sacrificed for analysis. Chronic-binge alcohol exposure induced an elevation in liver enzymes, steatosis and morphology changes, while LGG-s supplementation attenuated these changes. Treatment with LGG-s significantly improved intestinal barrier function reflected by increased mRNA expression of tight junction (TJ) proteins and villus-crypt histology in ileum, and decreased Escherichia coli (E. coli) protein level in liver. Importantly, flow cytometry analysis showed that alcohol reduced Treg cell population while increased TH17 cell population as well as IL-17 secretion, which was reversed by LGG-s administration. In conclusion, our findings indicate that LGG-s is effective in preventing chronic-binge alcohol exposure-induced liver injury and shed a light on the importance of the balance of Treg and TH17 cells in the role of LGG-s application. PMID:26617183

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

    PubMed Central

    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

    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 α-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 μmol/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 α-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

  12. Combination of alcohol and fructose exacerbates metabolic imbalance in terms of hepatic damage, dyslipidemia, and insulin resistance in rats.

    PubMed

    Alwahsh, Salamah Mohammad; Xu, Min; Schultze, Frank Christian; Wilting, Jörg; Mihm, Sabine; Raddatz, Dirk; Ramadori, Giuliano

    2014-01-01

    Although both alcohol and fructose are particularly steatogenic, their long-term effect in the development of a metabolic syndrome has not been studied in vivo. Consumption of fructose generally leads to obesity, whereas ethanol can induce liver damage in the absence of overweight. Here, Sprague-Dawley rats were fed ad libitum for 28 days on five diets: chow (control), liquid Lieber-DeCarli (LDC) diet, LDC +30%J of ethanol (L-Et) or fructose (L-Fr), and LDC combined with 30%J ethanol and 30%J fructose (L-EF). Body weight (BW) and liver weight (LW) were measured. Blood and liver samples were harvested and subjected to biochemical tests, histopathological examinations, and RT-PCR. Alcohol-containing diets substantially reduced the food intake and BW (≤3rd week), whereas fructose-fed animals had higher LW than controls (P<0.05). Additionally, leukocytes, plasma AST and leptin levels were the highest in the fructose-administered rats. Compared to the chow and LDC diets, the L-EF diet significantly elevated blood glucose, insulin, and total-cholesterol levels (also vs. the L-Et group). The albumin and Quick-test levels were the lowest, whereas ALT activity was the highest in the L-EF group. Moreover, the L-EF diet aggravated plasma triglyceride and reduced HDL-cholesterol levels more than 2.7-fold compared to the sum of the effects of the L-Et and L-Fr diets. The decreased hepatic insulin clearance in the L-EF group vs. control and LDC groups was reflected by a significantly decreased C-peptide:insulin ratio. All diets except the control caused hepatosteatosis, as evidenced by Nile red and H&E staining. Hepatic transcription of insulin receptor substrate-1/2 was mainly suppressed by the L-Fr and L-EF diets. The L-EF diet did not enhance the mitochondrial β-oxidation of fatty acids (Cpt1α and Ppar-α expressions) compared to the L-Et or L-Fr diet. Together, our data provide evidence for the coaction of ethanol and fructose with a high-fat-diet on dyslipidemia and

  13. The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model Mice

    PubMed Central

    Ideta, Takayasu; Shirakami, Yohei; Miyazaki, Tsuneyuki; Kochi, Takahiro; Sakai, Hiroyasu; Moriwaki, Hisataka; Shimizu, Masahito

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD), which is strongly associated with metabolic syndrome, is increasingly a major cause of hepatic disorder. Dipeptidyl peptidase (DPP)-4 inhibitors, anti-diabetic agents, are expected to be effective for the treatment of NAFLD. In the present study, we established a novel NAFLD model mouse using monosodium glutamate (MSG) and a high-fat diet (HFD) and investigated the effects of a DPP-4 inhibitor, teneligliptin, on the progression of NAFLD. Male MSG/HFD-treated mice were divided into two groups, one of which received teneligliptin in drinking water. Administration of MSG and HFD caused mice to develop severe fatty changes in the liver, but teneligliptin treatment improved hepatic steatosis and inflammation, as evaluated by the NAFLD activity score. Serum alanine aminotransferase and intrahepatic triglyceride levels were significantly decreased in teneligliptin-treated mice (p < 0.05). Hepatic mRNA levels of the genes involved in de novo lipogenesis were significantly downregulated by teneligliptin (p < 0.05). Moreover, teneligliptin increased hepatic expression levels of phosphorylated AMP-activated protein kinase (AMPK) protein. These findings suggest that teneligliptin attenuates lipogenesis in the liver by activating AMPK and downregulating the expression of genes involved in lipogenesis. DPP-4 inhibitors may be effective for the treatment of NAFLD and may be able to prevent its progression to non-alcoholic steatohepatitis. PMID:26670228

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

    PubMed Central

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

    2014-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases around the world, and is closely associated with obesity, diabetes, and insulin resistance. Ursolic acid (UA), an ubiquitous triterpenoid with multifold biological roles, is distributed in various plants. This study was conducted to investigate the therapeutic effect and potential mechanisms of UA against hepatic steatosis in a high-fat diet (HFD)-induced obese non-alcoholic fatty liver disease (NAFLD) rat model. Methodology/Principal Findings Obese NAFLD model was established in Sprague-Dawley rats by 8-week HFD feeding. Therapeutic role of UA was evaluated using 0.125%, 0.25%, 0.5% UA-supplemented diet for another 6 weeks. The results from both morphologic and histological detections indicated that UA significantly reversed HFD-induced hepatic steatosis and liver injury. Besides, hepatic peroxisome proliferator-activated receptor (PPAR)-α was markedly up-regulated at both mRNA and protein levels by UA. Knocking down PPAR-α 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-α 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

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

    PubMed Central

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

    2015-01-01

    Background Chronic and excessive alcohol consumption is an established risk for hepatic inflammation and carcinogenesis. Luteolin is one of the most common flavonoids present in plants and has potential beneficial effects against cancer. In this study, we examined the effect and potential mechanisms of luteolin supplementation in a carcinogen initiated alcohol-promoted pre-neoplastic liver lesion mouse model. Methods C57BL/6 mice were injected with diethylnitrosamine (DEN) [i.p. 25 mg/kg of body weight (BW)] at 14 days of age. At 8 weeks of age mice were group pair-fed with Lieber-DeCarli liquid control diet or alcoholic diet [ethanol (EtOH) diet, 27% total energy from ethanol] and supplemented with a dose of 30 mg luteolin/kg BW per day for 21 days. Results DEN-injected mice fed EtOH diet displayed a significant induction of pre-neoplastic lesions, a marker associated with presence of steatosis and inflammation. Dietary luteolin significantly reduced the severity and incidence of hepatic inflammatory foci and steatosis in DEN-injected mice fed EtOH diet, as well the presence of preneoplastic lesions. There was no difference on hepatic protein levels of sirtuin 1 (SIRT1) among all groups; however, luteolin supplementation significantly reversed alcohol-reduced SIRT1 activity assessed by the ratio of acetylated and total forkhead box protein O1 (FoXO1) and SIRT1 target proliferator-activated receptor gamma, coactivator 1 alpha (PGC1α). Conclusions Dietary intake of luteolin prevents alcohol promoted pre-neoplastic lesions, potentially mediated by SIRT1 signaling pathway. PMID:26005679

  16. Etiology of liver cirrhosis in Brazil: chronic alcoholism and hepatitis viruses in liver cirrhosis diagnosed in the state of Espírito Santo

    PubMed Central

    Gonçalves, Patricia Lofego; da Penha Zago-Gomes, Maria; Marques, Carla Couzi; Mendonça, Ana Tereza; Gonçalves, Carlos Sandoval; Pereira, Fausto Edmundo Lima

    2013-01-01

    OBJECTIVES: To report the etiology of liver cirrhosis cases diagnosed at the University Hospital in Vitoria, Espirito Santo, Brazil. METHODS: The medical charts of patients with liver cirrhosis who presented to the University Hospital in Vitoria were reviewed. Chronic alcoholism and the presence of hepatitis B or C infections (HBV and HCV, respectively) were pursued in all cases. RESULTS: The sample consisted of 1,516 cases (male:female ratio 3.5:1, aged 53.2±12.6 years). The following main etiological factors were observed: chronic alcoholism alone (39.7%), chronic alcoholism in association with HBV or HCV (16.1%), HCV alone (14.5%) and in association with alcoholism (8.6%) (total, 23.1%), and HBV alone (13.1%) and in association with alcoholism (7.5%, total 20.6%). The remaining etiologies included cryptogenic cases (9.8%) and other causes (6.0%). The mean patient age was lower and the male-to-female ratio was higher in the cirrhosis cases that were associated with alcoholism or HBV compared with other causes. Intravenous drug abuse and a history of surgery or blood transfusion were significantly associated with HCV infection. Hepatocellular carcinoma was present at the time of diagnosis in 15.4% of cases. Chronic alcoholism associated with HCV infection was significantly associated (p<0.001) with reduced age (at the time of cirrhosis diagnosis) and increased prevalence of hepatocellular carcinoma (p = 0.052). CONCLUSION: Alcoholism, HCV and HBV are the main factors associated with liver cirrhosis in the state of Espirito Santo. Chronic alcoholism associated with HCV infection reduced the age of patients at the time of liver cirrhosis diagnosis. PMID:23644846

  17. Effects of insulin resistance and hepatic lipid accumulation on hepatic mRNA expression levels of apoB, MTP and L-FABP in non-alcoholic fatty liver disease.

    PubMed

    Higuchi, Nobito; Kato, Masaki; Tanaka, Masatake; Miyazaki, Masayuki; Takao, Shinichiro; Kohjima, Motoyuki; Kotoh, Kazuhiro; Enjoji, Munechika; Nakamuta, Makoto; Takayanagi, Ryoichi

    2011-11-01

    Non-alcoholic fatty liver disease (NAFLD) is considered a hepatic manifestation of metabolic syndrome, which is known to be associated with insulin resistance (IR). NAFLD occurs when the rate of hepatic fatty acid uptake from plasma and de novo fatty acid synthesis is greater than the rate of fatty acid oxidation and excretion as very low-density lipoprotein (VLDL). To estimate the effects of IR on hepatic lipid excretion, mRNA expression levels of genes involved in VLDL assembly were analyzed in NAFLD liver. Twenty-two histologically proven NAFLD patients and 10 healthy control subjects were enrolled in this study. mRNA was extracted from liver biopsy samples and real-time PCR was performed to quantify the expression levels of apolipoprotein B (apoB), microsomal triglyceride transfer protein (MTP) and liver fatty-acid binding protein (L-FABP). Hepatic expression levels of the genes were compared between NAFLD patients and control subjects. In NAFLD patients, we also examined correlations between expression levels of the genes and metabolic factors, including IR, and the extent of obesity and hepatic lipid accumulation. Hepatic expression levels of apoB, MTP and L-FABP were significantly up-regulated in NAFLD patients compared to control subjects. The expression levels of MTP were correlated with those of apoB, but not with those of L-FABP. In the NAFLD liver, the expression levels of MTP were significantly reduced in patients with HOMA-IR >2.5. In addition, a significant reduction in MTP expression was observed in livers with advanced steatosis. Enhanced expression of genes involved in VLDL assembly may be promoted to release excess lipid from NAFLD livers. However, the progression of IR and hepatic steatosis may attenuate this compensatory process.

  18. Efficacy of curcumin to reduce hepatic damage induced by alcohol and thermally treated oil in rats.

    PubMed

    El-Deen, Nasr A M N; Eid, Mohamed

    2010-01-01

    The authors investigated the effect of curcumin on markers of oxidative stress and liver damage in rats that chronically ingested alcohol and heated oil. Nine groups of ten Wistar male rats received combinations of curcumin 100 mg/kg body weight daily, ethanol 5 mg/kg, 15% dietary sunflower oil and 15% heated sunflower oil for 12 weeks. Serum and liver tissue were collected. Groups 4-6, which had received compounds causing oxidative stress, showed increased serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, cholesterol, triglycerides, low density lipoprotein, very low density lipoprotein and reduced high density lipoprotein, protein and albumin, compared with the controls. Reductions were observed in glutathione peroxidase and reductase gene expression, superoxide dismutase activity, glutathione peroxidase activity, glutathione reductase activity, reduced glutathione concentration and catalase enzyme activity. Groups 7, 8 and 9 which received curcumin with heated oil, ethanol or both, showed lower elevations in serum and oxidative damage markers compared with the corresponding non-curcumin treated groups. It can be concluded that curcumin reduces markers of liver damage in rats treated with heated sunflower oil or ethanol.

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

    PubMed Central

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

    2014-01-01

    Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to <0.2% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 μg/g in the lungs of ethanol-fed mice as compared to 1.5 μg/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1α and spliced XBP1 were observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. PMID:24625836

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

    PubMed

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

    2014-06-01

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

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

    SciTech Connect

    Campion, Sarah N.; Tatis-Rios, Cristina; Augustine, Lisa M.; Goedken, Michael J.; Rooijen, Nico van; Cherrington, Nathan J.; Manautou, Jose E.

    2009-04-01

    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.

  2. Roux-En Y Gastric Bypass Results in Long-Term Remission of Hepatocyte Apoptosis and Hepatic Histological Features of Non-alcoholic Steatohepatitis

    PubMed Central

    Schneck, Anne-Sophie; Anty, Rodolphe; Patouraux, Stéphanie; Bonnafous, Stéphanie; Rousseau, Déborah; Lebeaupin, Cynthia; Bailly-Maitre, Beatrice; Sans, Arnaud; Tran, Albert; Gugenheim, Jean; Iannelli, Antonio; Gual, Philippe

    2016-01-01

    The long-term effects of bariatric surgery on non-alcoholic steatohepatitis (NASH), focusing on liver injury and hepatocyte apoptosis, are not well-established. We here performed a longitudinal study with paired liver biopsies of nine morbidly obese women (median BMI: 42 [38.7; 45.1] kg/m2) with NASH with a median follow-up of 55 [44; 75] months after laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. LRYGB surgery was associated with significant weight loss (median BMI loss −13.7 [−16.4; −9.5] kg/m2), improved hepatic steatosis in all patients (55.5% with total resolution), and resolution of hepatic inflammation and hepatocyte ballooning in 100 and 88.8% of cases, respectively. Alanine aminotransferase levels dropped to normal values while hepatic activated cleaved caspase-3 levels strongly decreased after a median follow-up of 55 months. Hepatocyte apoptosis, as evaluated by serum caspase-generated keratin-18 fragment, improved within the first year following LRYGB and these improvements persisted for at least 55 months. LRYGB in morbidly obese patients with NASH is thus associated with a long-lasting beneficial impact on hepatic steatohepatitis and hepatocyte death.

  3. Roux-En Y Gastric Bypass Results in Long-Term Remission of Hepatocyte Apoptosis and Hepatic Histological Features of Non-alcoholic Steatohepatitis

    PubMed Central

    Schneck, Anne-Sophie; Anty, Rodolphe; Patouraux, Stéphanie; Bonnafous, Stéphanie; Rousseau, Déborah; Lebeaupin, Cynthia; Bailly-Maitre, Beatrice; Sans, Arnaud; Tran, Albert; Gugenheim, Jean; Iannelli, Antonio; Gual, Philippe

    2016-01-01

    The long-term effects of bariatric surgery on non-alcoholic steatohepatitis (NASH), focusing on liver injury and hepatocyte apoptosis, are not well-established. We here performed a longitudinal study with paired liver biopsies of nine morbidly obese women (median BMI: 42 [38.7; 45.1] kg/m2) with NASH with a median follow-up of 55 [44; 75] months after laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. LRYGB surgery was associated with significant weight loss (median BMI loss −13.7 [−16.4; −9.5] kg/m2), improved hepatic steatosis in all patients (55.5% with total resolution), and resolution of hepatic inflammation and hepatocyte ballooning in 100 and 88.8% of cases, respectively. Alanine aminotransferase levels dropped to normal values while hepatic activated cleaved caspase-3 levels strongly decreased after a median follow-up of 55 months. Hepatocyte apoptosis, as evaluated by serum caspase-generated keratin-18 fragment, improved within the first year following LRYGB and these improvements persisted for at least 55 months. LRYGB in morbidly obese patients with NASH is thus associated with a long-lasting beneficial impact on hepatic steatohepatitis and hepatocyte death. PMID:27594839

  4. Roux-En Y Gastric Bypass Results in Long-Term Remission of Hepatocyte Apoptosis and Hepatic Histological Features of Non-alcoholic Steatohepatitis.

    PubMed

    Schneck, Anne-Sophie; Anty, Rodolphe; Patouraux, Stéphanie; Bonnafous, Stéphanie; Rousseau, Déborah; Lebeaupin, Cynthia; Bailly-Maitre, Beatrice; Sans, Arnaud; Tran, Albert; Gugenheim, Jean; Iannelli, Antonio; Gual, Philippe

    2016-01-01

    The long-term effects of bariatric surgery on non-alcoholic steatohepatitis (NASH), focusing on liver injury and hepatocyte apoptosis, are not well-established. We here performed a longitudinal study with paired liver biopsies of nine morbidly obese women (median BMI: 42 [38.7; 45.1] kg/m(2)) with NASH with a median follow-up of 55 [44; 75] months after laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. LRYGB surgery was associated with significant weight loss (median BMI loss -13.7 [-16.4; -9.5] kg/m(2)), improved hepatic steatosis in all patients (55.5% with total resolution), and resolution of hepatic inflammation and hepatocyte ballooning in 100 and 88.8% of cases, respectively. Alanine aminotransferase levels dropped to normal values while hepatic activated cleaved caspase-3 levels strongly decreased after a median follow-up of 55 months. Hepatocyte apoptosis, as evaluated by serum caspase-generated keratin-18 fragment, improved within the first year following LRYGB and these improvements persisted for at least 55 months. LRYGB in morbidly obese patients with NASH is thus associated with a long-lasting beneficial impact on hepatic steatohepatitis and hepatocyte death. PMID:27594839

  5. Oncogenic signaling pathways and origins of tumor-initiating stem-like cells of hepatocellular carcinomas induced by hepatitis C virus, alcohol and/or obesity.

    PubMed

    Chen, Chia-Lin; Tsukamoto, Hidekazu; Machida, Keigo

    2014-07-01

    This review article discusses the importance and oncogenic signaling pathways of tumor-initiating cells (TICs) in several etiologies of hepatocellular carcinomas (HCCs) induced by hepatitis C virus (HCV), alcohol, obesity and/or chemicals. Stem cells may be present in cancer tissue, and a hierarchy of cells is formed, as is the case for normal tissue. Tumor formation, growth and propagation are maintained by a small proportion of cells with stem cell-like properties. TICs are present in alcohol-fed HCV transgenic mice, diethylnitrosamine/phenobarbital-treated mice (chemical carcinogenesis) and Spnb2 +/- mice (defective TGF-β signal). Alcohol/obesity-associated endotoxemia induces the stem cell marker Nanog through TLR4 signaling to generate TICs and liver tumors in several HCC models. The oncogenic pathway (such as the STAT3 and TLR4-NANOG pathway) and mechanism of generation of TICs of HCCs associated with HCV, alcohol and obesity are discussed. Understanding the molecular stemness signaling and cellular hierarchy and defining key TIC-specific genes will accelerate the development of novel biomarkers and treatment strategies. This review highlights recent advances in understanding the pathogenesis of liver TICs and discusses unanswered questions about the concept of liver TICs. (This project was supported by NIH grants 1R01AA018857 and P50AA11999).

  6. Dissociation between exercise-induced reduction in liver fat and changes in hepatic and peripheral glucose homoeostasis in obese patients with non-alcoholic fatty liver disease.

    PubMed

    Cuthbertson, Daniel J; Shojaee-Moradie, Fariba; Sprung, Victoria S; Jones, Helen; Pugh, Christopher J A; Richardson, Paul; Kemp, Graham J; Barrett, Mark; Jackson, Nicola C; Thomas, E Louise; Bell, Jimmy D; Umpleby, A Margot

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is associated with multi-organ (hepatic, skeletal muscle, adipose tissue) insulin resistance (IR). Exercise is an effective treatment for lowering liver fat but its effect on IR in NAFLD is unknown. We aimed to determine whether supervised exercise in NAFLD would reduce liver fat and improve hepatic and peripheral (skeletal muscle and adipose tissue) insulin sensitivity. Sixty nine NAFLD patients were randomized to 16 weeks exercise supervision (n=38) or counselling (n=31) without dietary modification. All participants underwent MRI/spectroscopy to assess changes in body fat and in liver and skeletal muscle triglyceride, before and following exercise/counselling. To quantify changes in hepatic and peripheral insulin sensitivity, a pre-determined subset (n=12 per group) underwent a two-stage hyperinsulinaemic euglycaemic clamp pre- and post-intervention. Results are shown as mean [95% confidence interval (CI)]. Fifty participants (30 exercise, 20 counselling), 51 years (IQR 40, 56), body mass index (BMI) 31 kg/m(2) (IQR 29, 35) with baseline liver fat/water % of 18.8% (IQR 10.7, 34.6) completed the study (12/12 exercise and 7/12 counselling completed the clamp studies). Supervised exercise mediated a greater reduction in liver fat/water percentage than counselling [Δ mean change 4.7% (0.01, 9.4); P<0.05], which correlated with the change in cardiorespiratory fitness (r=-0.34, P=0.0173). With exercise, peripheral insulin sensitivity significantly increased (following high-dose insulin) despite no significant change in hepatic glucose production (HGP; following low-dose insulin); no changes were observed in the control group. Although supervised exercise effectively reduced liver fat, improving peripheral IR in NAFLD, the reduction in liver fat was insufficient to improve hepatic IR. PMID:26424731

  7. Hepatic Macrosteatosis Is Partially Converted to Microsteatosis by Melatonin Supplementation in ob/ob Mice Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Lavazza, Antonio; Golic, Igor; Aleksic, Marija; Korac, Aleksandra; Rodella, Luigi Fabrizio; Rezzani, Rita

    2016-01-01

    Background Obesity is a common risk factor for non-alcoholic fatty liver disease (NAFLD). Currently, there are no specific treatments against NAFLD. Thus, examining any molecule with potential benefits against this condition emerged melatonin as a molecule that influences metabolic dysfunctions. The aim of this study was to determine whether melatonin would function against NAFDL, studying morphological, ultrastuctural and metabolic markers that characterize the liver of ob/ob mice. Methods Lean and ob/ob mice were supplemented with melatonin in the drinking water for 8 weeks. Histology and stereology were performed to assess hepatic steatosis and glycogen deposition. Ultrastructural features of mitochondria, endoplasmic reticulum (ER) and their juxtapositions were evaluated in livers of all experimental groups. Furthermore, hepatic distribution and expression of markers of ER and mitochondria (calnexin, ATP sintase β, GRP78 and CHOP) and metabolic dysfunction (RPB4, β-catenin) and cellular longevity (SIRT1) were analyzed. Results Melatonin significantly reduced glycemia, identified also by a decrease of hepatic RBP4 expression, reversed macrosteatosis in microsteatosis at the hepatic pericentral zone, enlarged ER-mitochondrial distance and ameliorated the morphology and organization of these organelles in ob/ob mouse liver. Furthermore, in ob/ob mice, calnexin and ATP synthase β were partially restored, GRP78 and CHOP decreased in periportal and midzonal hepatocytes and β-catenin expression was, in part, restored in peripheral membranes of hepatocytes. Melatonin supplementation to ob/ob mice improves hepatic morphological, ultrastructural and metabolic damage that occurs as a result of NAFLD. Conclusions Melatonin may be a potential adjuvant treatment to limit NAFLD and its progression into irreversible complications. PMID:26824477

  8. Dissociation between exercise-induced reduction in liver fat and changes in hepatic and peripheral glucose homoeostasis in obese patients with non-alcoholic fatty liver disease.

    PubMed

    Cuthbertson, Daniel J; Shojaee-Moradie, Fariba; Sprung, Victoria S; Jones, Helen; Pugh, Christopher J A; Richardson, Paul; Kemp, Graham J; Barrett, Mark; Jackson, Nicola C; Thomas, E Louise; Bell, Jimmy D; Umpleby, A Margot

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is associated with multi-organ (hepatic, skeletal muscle, adipose tissue) insulin resistance (IR). Exercise is an effective treatment for lowering liver fat but its effect on IR in NAFLD is unknown. We aimed to determine whether supervised exercise in NAFLD would reduce liver fat and improve hepatic and peripheral (skeletal muscle and adipose tissue) insulin sensitivity. Sixty nine NAFLD patients were randomized to 16 weeks exercise supervision (n=38) or counselling (n=31) without dietary modification. All participants underwent MRI/spectroscopy to assess changes in body fat and in liver and skeletal muscle triglyceride, before and following exercise/counselling. To quantify changes in hepatic and peripheral insulin sensitivity, a pre-determined subset (n=12 per group) underwent a two-stage hyperinsulinaemic euglycaemic clamp pre- and post-intervention. Results are shown as mean [95% confidence interval (CI)]. Fifty participants (30 exercise, 20 counselling), 51 years (IQR 40, 56), body mass index (BMI) 31 kg/m(2) (IQR 29, 35) with baseline liver fat/water % of 18.8% (IQR 10.7, 34.6) completed the study (12/12 exercise and 7/12 counselling completed the clamp studies). Supervised exercise mediated a greater reduction in liver fat/water percentage than counselling [Δ mean change 4.7% (0.01, 9.4); P<0.05], which correlated with the change in cardiorespiratory fitness (r=-0.34, P=0.0173). With exercise, peripheral insulin sensitivity significantly increased (following high-dose insulin) despite no significant change in hepatic glucose production (HGP; following low-dose insulin); no changes were observed in the control group. Although supervised exercise effectively reduced liver fat, improving peripheral IR in NAFLD, the reduction in liver fat was insufficient to improve hepatic IR.

  9. Carvedilol Improves Inflammatory Response, Oxidative Stress and Fibrosis in the Alcohol-Induced Liver Injury in Rats by Regulating Kuppfer Cells and Hepatic Stellate Cells

    PubMed Central

    Leitão, Renata Ferreira de Carvalho; Brito, Gerly Anne de Castro; Miguel, Emilio de Castro; Guedes, Paulo Marcos Matta; de Araújo, Aurigena Antunes

    2016-01-01

    Aim To evaluate the anti-inflammatory, anti-oxidant and antifibrotic effects of carvedilol (CARV) in rats with ethanol-induced liver injury. Methods Liver injury was induced by gavage administration of alcohol (7 g/kg) for 28 consecutive days. Eighty Wistar rats were pretreated with oral CARV at 1, 3, or 5 mg/kg or with saline 1 h before exposure to alcohol. Liver homogenates were assayed for interleukin (IL)-1β, IL-10, and tumor necrosis factor (TNF)-α level as well as for myeloperoxidase (MPO) activity and malonyldialdehyde (MDA) and glutathione (GSH) levels. Serum aspartate aminotransferase (AST) activity and liver triglyceride (TG) levels were also assayed. Immunohistochemical analyses of cyclooxygenase 2 (COX-2), receptor activator of nuclear factor kappa-B/ligand (RANK/RANKL), suppressor of cytokine signalling (SOCS1), the Kupffer cell marker IBA-1 (ionized calcium-binding adaptor molecule 1), intercellular adhesion molecule 1 (ICAM-1), superoxide dismutase (SOD-1), and glutathione peroxidase (GPx-1) expression were performed. Confocal microscopy analysis of IL-1β and NF-κB expression and real-time quantitative PCR analysis for TNFα, PCI, PCIII, and NF-κB were performed. Results CARV treatment (5 mg/kg) during the alcohol exposure protocol was associated with reduced steatosis, hepatic cord degeneration, fibrosis and necrosis, as well as reduced levels of AST (p < 0.01), ALT (p < 0.01), TG (p < 0.001), MPO (p < 0.001), MDA (p < 0.05), and proinflammatory cytokines (IL-1β and TNF-α, both p < 0.05), and increased levels of the anti-inflammatory cytokine IL-10 (p < 0.001) and GSH (p < 0.05), compared to the alcohol-only group. Treatment with CARV 5 mg/kg also reduced expression levels of COX-2, RANK, RANKL, IBA-1, and ICAM-1 (all p < 0.05), while increasing expression of SOCS1, SOD-1, and GPx-1 (all p < 0.05) and decreasing expression of IL-1β and NF-κB (both, p < 0.05). Real-time quantitative PCR analysis showed that mRNA production of TNF

  10. Difference in Hepatic Metabolism of Long- and Medium-Chain Fatty Acids: the Role of Fatty Acid Chain Length in the Production of the Alcoholic Fatty Liver*

    PubMed Central

    Lieber, Charles S.; Lefèvre, André; Spritz, Norton; Feinman, Lawrence; DeCarli, Leonore M.

    1967-01-01

    Replacement of dietary triglycerides containing long-chain fatty acids (LCFA) by triglycerides containing medium-chain fatty acids (MCFA) markedly reduced the capacity of alcohol to produce fatty liver in rats. After 24 days of ethanol and MCFA, the increase in hepatic triglycerides was only 3 times that of controls, whereas an 8-fold rise was observed after ethanol and LCFA. The triglyceride fatty acids that accumulated in the liver after feeding of ethanol with MCFA contained only a small percentage of the MCFA; their composition also differed strikingly from that of adipose lipids. To study the mechanism of the reduction in steatosis, we compared oxidation to CO2 and incorporation into esterified lipids of 14C-labeled chylomicrons or palmitate-14C (representing LCFA), and of octanoate-14C (as MCFA) in liver slices and isolated perfused livers, in the presence or absence of ethanol. Ethanol depressed the oxidation of all substrates to CO2; MCFA, however, was much more oxidized and reciprocally much less esterified than LCFA, with a 100-fold difference in the ratio of esterified lipid-14C to 14CO2. Furthermore, in hepatic microsomal fractions incubated with α-glycerophosphate, octanoate was much less esterified than palmitate. This propensity of MCFA to oxidation rather than esterification represents a likely explanation for the reduction in alcoholic steatosis upon replacement of dietary LCFA by MCFA. PMID:6036539

  11. Caffeine protects against alcohol-induced liver fibrosis by dampening the cAMP/PKA/CREB pathway in rat hepatic stellate cells.

    PubMed

    Wang, Qi; Dai, Xuefei; Yang, Wanzhi; Wang, He; Zhao, Han; Yang, Feng; Yang, Yan; Li, Jun; Lv, Xiongwen

    2015-04-01

    Alcoholic liver fibrosis (ALF) is characterized by hyperplasia of extracellular matrix under long-term alcohol stimulation. Hepatic stellate cell (HSC) activation plays an important role in promoting hepatic fibrogenesis. Caffeine, as the main active component of coffee and tea, was widely consumed in daily life. It was always a thought that caffeine can reduce the probability of suffering from liver diseases. In this study, we attempt to validate the hypothesis that caffeine inhibits activation of HSCs which were isolated from rat ALF model. The rats were gavaged by ethanol to establish ALF model and then treated with different concentrations of caffeine or colchicine. Serum was collected to measure the contents of serum alanine aminotransferase (ALT), aspartate transaminase (AST), hyaluronic acid (HA), laminin (LN), N-terminal peptide of type III procollagen (PIIINP) and type IV collagen (CIV). Then liver tissues were obtained for hematoxylin-eosin staining and Sirius-red staining. Others were treated through liver perfusion to isolate primary rat HSCs. Interestingly, we found that caffeine significantly decreased ALT, AST, HA, LN, PIIINP and CIV levels and reversed liver fibrosis in rat ALF models. Results of immunohistochemistry, real-time PCR and western blot indicated that caffeine could reduce fibrosis and inhibit cAMP/PKA/CREB signal pathway in HSC. Caffeine has a preventive effect on ALF. The mechanism may be interpreted that caffeine inhibits the cAMP/PKA/CREB signal pathway through adenosine A2A receptors in HSC.

  12. Cellular cholesterol accumulation modulates high fat high sucrose (HFHS) diet-induced ER stress and hepatic inflammasome activation in the development of non-alcoholic steatohepatitis.

    PubMed

    Bashiri, Amir; Nesan, Dinushan; Tavallaee, Ghazaleh; Sue-Chue-Lam, Ian; Chien, Kevin; Maguire, Graham F; Naples, Mark; Zhang, Jing; Magomedova, Lilia; Adeli, Khosrow; Cummins, Carolyn L; Ng, Dominic S

    2016-07-01

    Non-alcoholic steatohepatitis (NASH), is the form of non-alcoholic fatty liver disease posing risk to progress into serious long term complications. Human and pre-clinical models implicate cellular cholesterol dysregulation playing important role in its development. Mouse model studies suggest synergism between dietary cholesterol and fat in contributing to NASH but the mechanisms remain poorly understood. Our laboratory previously reported the primary importance of hepatic endoplasmic reticulum cholesterol (ER-Chol) in regulating hepatic ER stress by comparing the responses of wild type, Ldlr-/-xLcat+/+ and Ldlr-/-xLcat-/- mice, to a 2% high cholesterol diet (HCD). Here we further investigated the roles of ER-Chol and ER stress in HFHS diet-induced NASH using the same strains. With HFHS diet feeding, both WT and Ldlr-/-xLcat+/+ accumulate ER-Chol in association with ER stress and inflammasome activation but the Ldlr-/-xLcat-/- mice are protected. By contrast, all three strains accumulate cholesterol crystal, in correlation with ER-Chol, albeit less so in Ldlr-/-xLcat-/- mice. By comparison, HCD feeding per se (i) is sufficient to promote steatosis and activate inflammasomes, and (ii) results in dramatic accumulation of cholesterol crystal which is linked to inflammasome activation in Ldlr-/-xLcat-/- mice, independent of ER-Chol. Our data suggest that both dietary fat and cholesterol each independently promote steatosis, cholesterol crystal accumulation and inflammasome activation through distinct but complementary pathways. In vitro studies using palmitate-induced hepatic steatosis in HepG2 cells confirm the key roles by cellular cholesterol in the induction of steatosis and inflammasome activations. These novel findings provide opportunities for exploring a cellular cholesterol-focused strategy for treatment of NASH. PMID:27090939

  13. The non-invasive 13C-methionine breath test detects hepatic mitochondrial dysfunction as a marker of disease activity in non-alcoholic steatohepatitis

    PubMed Central

    2011-01-01

    Introduction Mitochondrial dysfunction plays a central role in the general pathogenesis of non-alcoholic fatty liver disease (NAFLD), increasing the risk of developing steatosis and subsequent hepatocellular inflammation. We aimed to assess hepatic mitochondrial function by a non-invasive 13C-methionine breath test (MeBT) in patients with histologically proven NAFLD. Methods 118 NAFLD-patients and 18 healthy controls were examined by MeBT. Liver biopsy specimens were evaluated according to the NASH scoring system. Results Higher grades of NASH activity and fibrosis were independently associated with a significant decrease in cumulative 13C-exhalation (expressed as cPDR(%)). cPDR1.5h was markedly declined in patients with NASH and NASH cirrhosis compared to patients with simple steatosis or borderline diagnosis (cPDR1.5h: 3.24 ± 1.12% and 1.32 ± 0.94% vs. 6.36 ± 0.56% and 4.80 ± 0.88% respectively; p < 0.001). 13C-exhalation further declined in the presence of advanced fibrosis which was correlated with NASH activity (r = 0.36). The area under the ROC curve (AUROC) for NASH diagnosis was estimated to be 0.87 in the total cohort and 0.83 in patients with no or mild fibrosis (F0-1). Conclusion The 13C-methionine breath test indicates mitochondrial dysfunction in non-alcoholic fatty liver disease and predicts higher stages of disease activity. It may, therefore, be a valuable diagnostic addition for longitudinal monitoring of hepatic (mitochondrial) function in non-alcoholic fatty liver disease. PMID:21810560

  14. Drug treatment clients' readiness for hepatitis C treatment: implications for expanding treatment services in drug and alcohol settings.

    PubMed

    Treloar, Carla; Holt, Martin

    2008-08-01

    This study explores the perception of and readiness for hepatitis C treatment within a sample of 77 clients already participating in drug treatment, with a view to identifying likely barriers and incentives to hepatitis C treatment within a drug treatment population. Participants with hepatitis C did not demonstrate a consistent, indepth knowledge of the infection, lacked confidence in symptom recognition, and had little awareness of treatment options. Those without obvious symptoms or liver deterioration did not have a pressing interest in treatment, and many had heard concerning stories about the side effects of hepatitis C treatment. For those coping with anxiety or depression, the increased risk of a depressive episode under interferon treatment was a major barrier to treatment. PMID:18666886

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

    SciTech Connect

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

    2014-06-01

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

  16. Molecular Links between Alcohol and Tobacco Induced DNA Damage, Gene Polymorphisms and Patho-physiological Consequences: A Systematic Review of Hepatic Carcinogenesis.

    PubMed

    Mansoori, Abdul Anvesh; Jain, Subodh Kumar

    2015-01-01

    Chronic alcohol and tobacco abuse plays a crucial role in the development of different liver associated disorders. Intake promotes the generation of reactive oxygen species within hepatic cells exposing their DNA to continuous oxidative stress which finally leads to DNA damage. However in response to such damage an entangled protective repair machinery comprising different repair proteins like ATM, ATR, H2AX, MRN complex becomes activated. Under abnormal conditions the excessive reactive oxygen species generation results in genetic predisposition of various genes (as ADH, ALDH, CYP2E1, GSTT1, GSTP1 and GSTM1) involved in xenobiotic metabolic pathways, associated with susceptibility to different liver related diseases such as fibrosis, cirrhosis and hepatocellular carcinoma. There is increasing evidence that the inflammatory process is inherently associated with many different cancer types, including hepatocellular carcinomas. The generated reactive oxygen species can also activate or repress epigenetic elements such as chromatin remodeling, non-coding RNAs (micro-RNAs), DNA (de) methylation and histone modification that affect gene expression, hence leading to various disorders. The present review provides comprehensive knowledge of different molecular mechanisms involved in gene polymorphism and their possible association with alcohol and tobacco consumption. The article also showcases the necessity of identifying novel diagnostic biomarkers for early cancer risk assessment among alcohol and tobacco users. PMID:26163595

  17. Molecular Links between Alcohol and Tobacco Induced DNA Damage, Gene Polymorphisms and Patho-physiological Consequences: A Systematic Review of Hepatic Carcinogenesis.

    PubMed

    Mansoori, Abdul Anvesh; Jain, Subodh Kumar

    2015-01-01

    Chronic alcohol and tobacco abuse plays a crucial role in the development of different liver associated disorders. Intake promotes the generation of reactive oxygen species within hepatic cells exposing their DNA to continuous oxidative stress which finally leads to DNA damage. However in response to such damage an entangled protective repair machinery comprising different repair proteins like ATM, ATR, H2AX, MRN complex becomes activated. Under abnormal conditions the excessive reactive oxygen species generation results in genetic predisposition of various genes (as ADH, ALDH, CYP2E1, GSTT1, GSTP1 and GSTM1) involved in xenobiotic metabolic pathways, associated with susceptibility to different liver related diseases such as fibrosis, cirrhosis and hepatocellular carcinoma. There is increasing evidence that the inflammatory process is inherently associated with many different cancer types, including hepatocellular carcinomas. The generated reactive oxygen species can also activate or repress epigenetic elements such as chromatin remodeling, non-coding RNAs (micro-RNAs), DNA (de) methylation and histone modification that affect gene expression, hence leading to various disorders. The present review provides comprehensive knowledge of different molecular mechanisms involved in gene polymorphism and their possible association with alcohol and tobacco consumption. The article also showcases the necessity of identifying novel diagnostic biomarkers for early cancer risk assessment among alcohol and tobacco users.

  18. Deletion of SIRT1 from Hepatocytes in Mice Disrupts Lipin-1 Signaling and Aggravates Alcoholic Fatty liver

    PubMed Central

    Yin, Huquan; Hu, Ming; Liang, Xiaomei; Ajmo, Joanne M.; Li, Xiaoling; Bataller, Ramon; Odena, Gemma; Stevens, Stanley M.; You, Min

    2013-01-01

    Background&Aims: Sirtuin (SIRT1) is a NAD+-dependent protein deacetylase that regulates hepatic lipid metabolism by modifying histones and transcription factors. Ethanol exposure disrupts SIRT1 activity and contributes to alcoholic liver disease (ALD) in rodents, but the exact pathogenic mechanism is not clear. We compared mice with liver-specific deletion of Sirt1 (Sirt1LKO) mice with their LOX littermates (controls). Methods: We induced alcoholic liver injury in male Sirt1LKO and control mice, placing them on Lieber-DeCarli ethanol-containing diets for 10 days and then administering a single dose of ethanol (5 g/kg body weight) via gavage. Liver and serum samples were collected. We also measured mRNA levels of SIRT1, SFRS10, and lipin-1β and lipin-1α in liver samples from patients with alcoholic hepatitis (AH) and individuals without AH (controls). Results: On the ethanol-containing diet, livers of Sirt1LKO mice accumulated larger amounts of hepatic lipid and expressed higher levels of inflammatory cytokines than control mice; serum of Sirt1LKO mice had increased levels of alanine aminotransferase and aspartate aminotransferase. Hepatic deletion of SIRT1 exacerbated ethanol-mediated defects in lipid metabolism, mainly by altering the function of lipin-1, a transcriptional regulator of lipid metabolism. In cultured mouse AML-12 hepatocytes, transgenic expression of SIRT1 prevented fat accumulation in response to ethanol exposure, largely by reversing the aberrations in lipin-1 signaling induced by ethanol. Liver samples from patients with AH had reduced levels of SIRT1 and a higher ratio of Lpin1β:α mRNAs than controls. Conclusions: In mice, hepatic deletion of Sirt1 promotes steatosis, inflammation, and fibrosis in response to ethanol challenge. Ethanol-mediated impairment of hepatic SIRT1 signaling via lipin-1 contributes to development of alcoholic steatosis and inflammation. Reagents designed to increase SIRT1 regulation of lipin-1 might be developed to

  19. Studies on the role of the Ah receptor in hexachloro-benzene-induced porphyria

    SciTech Connect

    Hahn, M.E.

    1987-01-01

    Many of the effects of hexachlorobenzene (HCB) resemble those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), whose effects are initiated by its binding to the AH receptor, the regulatory gene product of the Ah locus. I investigated the ability of HCB to interact with the AH receptor and the involvement of this protein in HCB-induced porphyria. The induction of two cytochrome P450 isozymes regulated by the Ah locus was also examined in light of their possible role in the pathogenesis of HCB- and TCDD-induced porphyria. HCB competitively inhibited the in vitro specific binding of ({sup 3}H)-TCDD to the rat hepatic Ah receptor (K{sub I} = 2.1 {mu}M) without affecting the solubility of ({sup 3}H)TCDD. Following the administration of HCB to rats, the number of ({sup 3}H)TCDD specific binding sites was reduced by up to 40%. HCB induced cytochromes P450b, P450e, P450c, and P450d, confirming that it is a mixed-type P450 inducer. The presence of porphyria in mice was assessed by measuring urinary and hepatic porphyrins and hepatic uroporphyrinogen decarboxylase activity.

  20. Simulation studies for wells AH-4bis/AH-17 and AH-18, Ahuachapan Geothermal Field

    SciTech Connect

    Monterrosa, Manuel Ernesto

    1996-01-24

    Well AH-4bis, at the Ahuachapan Geothermal Field is planned to be drilled on the same pad as the former AH-4. A simulation study was carried out for two casing dameters 13 5/8 and 9 5/8” in order to estimate its production and to know its economic feasibility. The simulation results indcate a high probability of production in the range of 7 Mwe, equivalent to 120 kg/s total mass flow rate, 1250 kJ/kg at 6 bar-a for the new well AH-4bis. Well AH- 17 is good producer, during 1991 after ten years of production, the well was shut-in due to silica scaling problems. A wellbore simulation was carried out in order to predict the new production conditions after the work-over, mainly to estimate the water flow rate in order to reduce the silica scaling. The results indicate a very low water flow rate. The match between the simulated and measured production curves after the work-over was successful. The well AH-18 is located at the southern part of the actual bore field. CEL is planning to expand the borefield at this area and it is neccessary to estimate the possible production condtions at that zone. The results indicate a high probabilty of production at that area. The power potential is estimated at 3.5 Mwe per well at WHP 6 bar-a and the wells will not require induction.

  1. 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

    Zorzano, A. ); Herrera, E. )

    1990-01-01

    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.

  2. Effects of the new thiazolidine derivative LPSF/GQ-02 on hepatic lipid metabolism pathways in non-alcoholic fatty liver disease (NAFLD).

    PubMed

    Araújo, Shyrlene; Soares E Silva, Amanda; Gomes, Fabiana; Ribeiro, Edlene; Oliveira, Wilma; Oliveira, Amanda; Lima, Ingrid; Lima, Maria do Carmo; Pitta, Ivan; Peixoto, Christina

    2016-10-01

    Non-alcoholic fatty liver disease (NAFLD) is considered the most common manifestation of metabolic syndrome. One of its most important features is the accumulation of triglycerides in the hepatocyte cells. Thiazolidinediones (TZDs) act as insulin sensitizers and are used to treat patients with type 2 diabetes and other conditions that are resistant to insulin, such as hepatic steatosis. Controversially, TZDs are also associated with the development of cardiovascular events and liver problems. For this reason, new therapeutic strategies are necessary to improve liver function in patients with chronic liver diseases. The aim of the present study was to evaluate the effects of LPSF/GQ-02 on the liver lipid metabolism in a murine model of NAFLD. Eighty male LDLR-/- mice were divided into 3 groups: 1-fed with a high-fat diet (HFD); 2-HFD+Pioglitazone (20mg/kg/day); 3-HFD+LPSF/GQ-02 (30mg/kg/day). The experiments lasted 12 weeks and drugs were administered daily by gavage in the final four weeks. The liver was processed for optical microscopy, Oil Red O, immunohistochemistry, immunofluorescence and western blot analysis. LPSF/GQ-02 effectively decreased fat accumulation, increased the hepatic levels of p-AMPK, FoxO1, ATGL, p-ACC and PPARα, and reduced the expression of LXRα, SREBP-1c and ACC. These results suggest that LPSF/GQ-02 acts directly on the hepatic lipid metabolism through the activation of the PPAR-α/AMPK/FoxO1/ATGL lipolytic pathway, and the inhibition of the AMPK/LXR/SREBP-1c/ACC/FAS lipogenic pathway.

  3. Type 2 Diabetes in Non-Alcoholic Fatty Liver Disease and Hepatitis C Virus Infection—Liver: The “Musketeer” in the Spotlight

    PubMed Central

    Ballestri, Stefano; Nascimbeni, Fabio; Romagnoli, Dante; Baldelli, Enrica; Targher, Giovanni; Lonardo, Amedeo

    2016-01-01

    The pathogenesis of type 2 diabetes (T2D) involves chronic hyperinsulinemia due to systemic and hepatic insulin resistance (IR), which if uncorrected, will lead to progressive pancreatic beta cell failure in predisposed individuals. Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of fatty (simple steatosis and steatohepatitis) and non-fatty liver changes (NASH-cirrhosis with or without hepatocellular carcinoma (HCC)) that are commonly observed among individuals with multiple metabolic derangements, notably including visceral obesity, IR and T2D. Hepatitis C virus (HCV) infection is also often associated with both hepatic steatosis and features of a specific HCV-associated dysmetabolic syndrome. In recent years, the key role of the steatotic liver in the development of IR and T2D has been increasingly recognized. Thus, in this comprehensive review we summarize the rapidly expanding body of evidence that links T2D with NAFLD and HCV infection. For each of these two liver diseases with systemic manifestations, we discuss the epidemiological burden, the pathophysiologic mechanisms and the clinical implications. To date, substantial evidence suggests that NAFLD and HCV play a key role in T2D development and that the interaction of T2D with liver disease may result in a “vicious circle”, eventually leading to an increased risk of all-cause mortality and liver-related and cardiovascular complications. Preliminary evidence also suggests that improvement of NAFLD is associated with a decreased incidence of T2D. Similarly, the prevention of T2D following HCV eradication in the era of direct-acting antiviral agents is a biologically plausible result. However, additional studies are required for further clarification of mechanisms involved. PMID:27005620

  4. Hepatic Deletion of Smad7 in Mouse Leads to Spontaneous Liver Dysfunction and Aggravates Alcoholic Liver Injury

    PubMed Central

    Zhu, Lu; Wang, Lingdi; Wang, Xiao; Luo, Xiaolin; Yang, Ling; Zhang, Rui; Yin, Hongkun; Xie, Dong; Pan, Yi; Chen, Yan

    2011-01-01

    Background TGF-β has been known to play an important role in various liver diseases including fibrosis and alcohol-induced fatty liver. Smad7 is an intracellular negative regulator of TGF-β signaling. It is currently unclear whether endogenous Smad7 has an effect on liver function and alcoholic liver damage. Methodology/Principal Findings We used Cre/loxP system by crossing Alb-Cre mice with Smad7loxP/loxP mice to generate liver-specific deletion of Smad7 with loss of the indispensable MH2 domain. Alcoholic liver injury was achieved by feeding mice with a liquid diet containing 5% ethanol for 6 weeks, followed by a single dose of ethanol gavage. Deletion of Smad7 in the liver was associated with increased Smad2/3 phosphorylation in the liver or upon TGF-β treatment in primary hepatocytes. The majority of mice with liver specific deletion of Smad7 (Smad7liver-KO) were viable and phenotypically normal, accompanied by only slight or no reduction of Smad7 expression in the liver. However, about 30% of Smad7liver-KO mice with high efficiency of Smad7 deletion had spontaneous liver dysfunction, demonstrated as low body weight, overall deterioration, and increased serum levels of AST and ALT. Degeneration and elevated apoptosis of liver cells were observed with these mice. TGF-β-induced epithelial to mesenchymal transition (EMT) was accelerated in Smad7-deleted primary hepatocytes. In addition, alcohol-induced liver injury and steatosis were profoundly aggravated in Smad7 deficient mice, associated with upregulation of critical genes involved in lipogenesis and inflammation. Furthermore, alcohol-induced ADH1 expression was significantly abrogated by Smad7 deletion in hepatocytes. Conclusion/Significance In this study, we provided in vivo evidence revealing that endogenous Smad7 plays an important role in liver function and alcohol-induced liver injury. PMID:21386907

  5. Exosomes derived from alcohol-treated hepatocytes horizontally transfer liver specific miRNA-122 and sensitize monocytes to LPS

    PubMed Central

    Momen-Heravi, Fatemeh; Bala, Shashi; Kodys, Karen; Szabo, Gyongyi

    2015-01-01

    Hepatocyte damage and inflammation in monocytes/macrophages are central to the pathogenesis of alcoholic hepatitis (AH). MicroRNAs (miRNAs) regulate all of these processes. MiRNA-122 is abundantly expressed in hepatocytes while monocytes/macrophages have low levels. The role of exosomes in AH and possible cross talk between hepatocyte-derived exosomes and immune cells is not explored yet. Here, we show that the number of exosomes significantly increases in the sera of healthy individuals after alcohol binge drinking and in mice after binge or chronic alcohol consumption. Exosomes isolated from sera after alcohol consumption or from in vitro ethanol-treated hepatocytes contained miRNA-122. Exosomes derived from ethanol-treated Huh7.5 cells were taken up by the recipients THP1 monocytes and horizontally transferred a mature form of liver-specific miRNA-122. In vivo, liver mononuclear cells and Kupffer cells from alcohol-fed mice had increased miRNA-122 levels. In monocytes, miRNA-122 transferred via exosomes inhibited the HO-1 pathway and sensitized to LPS stimulation and increased levels of pro-inflammatory cytokines. Finally, inflammatory effects of exosomes from ethanol-treated hepatocytes were prevented by using RNA interference via exosome-mediated delivery of a miRNA-122 inhibitor. These results demonstrate that first, exosomes mediate communication between hepatocytes and monocytes/macrophages and second, hepatocyte-derived miRNA-122 can reprogram monocytes inducing sensitization to LPS. PMID:25973575

  6. Diagnostic value of biochemical markers (NashTest) for the prediction of non alcoholo steato hepatitis in patients with non-alcoholic fatty liver disease

    PubMed Central

    Poynard, Thierry; Ratziu, Vlad; Charlotte, Frederic; Messous, Djamila; Munteanu, Mona; Imbert-Bismut, Françoise; Massard, Julien; Bonyhay, Luninita; Tahiri, Mohamed; Thabut, Dominique; Cadranel, Jean François; Le Bail, Brigitte; de Ledinghen, Victor

    2006-01-01

    Background Liver biopsy is considered the gold standard for assessing histologic lesions of non-alcoholic fatty liver disease (NAFLD). The aim was to develop and validate a new biomarker of non alcoholic steato hepatitis (NASH) the NashTest (NT) in patients with NAFLD. Methods 160 patients with NAFLD were prospectively included in a training group, 97 were included in a multicenter validation group and 383 controls. Histological diagnoses used Kleiner et al's scoring system, with 3 classes for NASH: "Not NASH", "Borderline", "NASH"). The area under the ROC curves (AUROC), sensitivity (Se), specificity (Sp), and positive and negative predictive values (PPV, NPV) were assessed. Results NT was developed using patented algorithms combining 13 parameters: age, sex, height, weight, and serum levels of triglycerides, cholesterol, alpha2macroglobulin, apolipoprotein A1, haptoglobin, gamma-glutamyl-transpeptidase, transaminases ALT, AST, and total bilirubin. AUROCs of NT for the diagnosis of NASH in the training and validation groups were, respectively, 0.79 (95%CI 0.69–0.86) and 0.79 (95%CI 0.67–0.87; P = 0.94); for the diagnosis of borderline NASH they were: 0.69 (95%CI 0.60–0.77) and 0.69 (95%CI 0.57–0.78; P = 0.98) and for the diagnosis of no NASH, 0.77 (95%CI 0.68–0.84) and 0.83 (95%CI 0.67–0.90; P = 0.34). When the two groups were pooled together the NashTest Sp for NASH = 94% (PPV = 66%), and Se = 33% (NPV = 81%); for borderline NASH or NASH Sp = 50% (PPV = 74%) and Se = 88% (NPV = 72%). Conclusion In patients with non-alcoholic fatty liver disease, NashTest, a simple and non-invasive biomarker reliably predicts the presence or absence of NASH. PMID:17096854

  7. Non-invasive diagnosis of alcoholic liver disease

    PubMed Central

    Mueller, Sebastian; Seitz, Helmut Karl; Rausch, Vanessa

    2014-01-01

    Alcoholic liver disease (ALD) is the most common liver disease in the Western world. For many reasons, it is underestimated and underdiagnosed. An early diagnosis is absolutely essential since it (1) helps to identify patients at genetic risk for ALD; (2) can trigger efficient abstinence namely in non-addicted patients; and (3) initiate screening programs to prevent life-threatening complications such as bleeding from varices, spontaneous bacterial peritonitis or hepatocellular cancer. The two major end points of ALD are alcoholic liver cirrhosis and the rare and clinically-defined alcoholic hepatitis (AH). The prediction and early diagnosis of both entities is still insufficiently solved and usually relies on a combination of laboratory, clinical and imaging findings. It is not widely conceived that conventional screening tools for ALD such as ultrasound imaging or routine laboratory testing can easily overlook ca. 40% of manifest alcoholic liver cirrhosis. Non-invasive methods such as transient elastography (Fibroscan), acoustic radiation force impulse imaging or shear wave elastography have significantly improved the early diagnosis of alcoholic cirrhosis. Present algorithms allow either the exclusion or the exact definition of advanced fibrosis stages in ca. 95% of patients. The correct interpretation of liver stiffness requires a timely abdominal ultrasound and actual transaminase levels. Other non-invasive methods such as controlled attenuation parameter, serum levels of M30 or M65, susceptometry or breath tests are under current evaluation to assess the degree of steatosis, apoptosis and iron overload in these patients. Liver biopsy still remains an important option to rule out comorbidities and to confirm the prognosis namely for patients with AH. PMID:25356026

  8. A novel role for the dioxin receptor in fatty acid metabolism and hepatic steatosis

    PubMed Central

    Lee, Jung Hoon; Wada, Taira; Febbraio, Maria; He, Jinhan; Matsubara, Tsutomu; Lee, Min Jae; Gonzalez, Frank J.; Xie, Wen

    2010-01-01

    Background & Aims The aryl hydrocarbon receptor (AhR) is a PAS domain transcription factor previously known as the “dioxin receptor” or “xenobiotic receptor.” The goal of this study is to determine the endobiotic role of AhR in hepatic steatosis. Methods Wild type, constitutively activated AhR (CA-AhR) transgenic, AhR null (AhR-/-), and fatty acid translocase CD36/FAT null (CD36-/-) mice were used to investigate the role of AhR in steatosis and the involvement of CD36 in the steatotic effect of AhR. The promoters of the mouse and human CD36 genes were cloned and their regulation by AhR was analyzed. Results Activation of AhR induced spontaneous hepatic steatosis characterized by the accumulation of triglycerides. The steatotic effect of AhR is likely due to the combined upregulation of CD36 and fatty acid transport proteins (FATPs), suppression of fatty acid oxidation, inhibition of hepatic export of triglycerides, increase in peripheral fat mobilization, and increased hepatic oxidative stress. Promoter analysis established CD36 as a novel transcriptional target of AhR. Activation of AhR in liver cells induced CD36 gene expression and enhanced fatty acid uptake. The steatotic effect of an AhR agonist was inhibited in CD36-/- mice. Conclusions Our study reveals a novel link between AhR-induced steatosis and the expression of CD36. Industrial or military exposures to dioxin and related compounds have been linked to increased prevalence of fatty liver in humans. Results from this study may help to establish AhR and its target CD36 as novel therapeutic and preventive targets for fatty liver disease. PMID:20303349

  9. Dioscin alleviates alcoholic liver fibrosis by attenuating hepatic stellate cell activation via the TLR4/MyD88/NF-κB signaling pathway

    PubMed Central

    Liu, Min; Xu, Youwei; Han, Xu; Yin, Lianhong; Xu, Lina; Qi, Yan; Zhao, Yanyan; Liu, Kexin; Peng, Jinyong

    2015-01-01

    The present work aimed to investigate the activities and underlying mechanisms of dioscin against alcoholic liver fibrosis (ALF). In vivo liver fibrosis in mice was induced by an alcoholic liquid diet, and in vitro studies were performed on activated HSC-T6 and LX2 cells treated with lipopolysaccharide. Our results showed that dioscin significantly attenuated hepatic stellate cells (HSCs) activation, improved collagen accumulation, and attenuated inflammation through down-regulating the levels of myeloid differentiation factor 88 (MyD88), nuclear factor κB (NF-κB), interleukin (IL)-1, IL-6 and tumour necrosis factor-α by decreasing Toll-like receptor (TLR)4 expression both in vivo and in vitro. TLR4 overexpression was also decreased by dioscin, leading to the markedly down-regulated levels of MyD88, NF-κB, transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (α-SMA) and type I collagen (COL1A1) in cultured HSCs. Suppression of cellular MyD88 by ST2825 or abrogation of NF-κB by pyrrolidine dithiocarbamate eliminated the inhibitory effects of dioscin on the levels of TGF-β1, α-SMA and COL1A1. In a word, dioscin exhibited potent effects against ALF via altering TLR4/MyD88/NF-κB signaling pathway, which provided novel insights into the mechanisms of this compound as an antifibrogenic candidate for the treatment of ALF in the future. PMID:26655640

  10. RESULTS FROM THE AHS PESTICIDE EXPOSURE STUDY

    EPA Science Inventory

    The Agricultural Health Study/Pesticide Exposure Study (AHS/PES) measured exposures resulting from agricultural use of 2,4-D and chlorpyrifos for a subset of applicators in the AHS cohort. Through on-farm measurements and observations, data collected in the exposure study will...

  11. Alcoholic liver disease: Treatment

    PubMed Central

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

    2014-01-01

    The excess consumption of alcohol is associated with alcoholic liver diseases (ALD). ALD is a major healthcare problem, personal and social burden, and significant reason for economic loss worldwide. The ALD spectrum includes alcoholic fatty liver, alcoholic hepatitis, cirrhosis, and the development of hepatocellular carcinoma. The diagnosis of ALD is based on a combination of clinical features, including a history of significant alcohol intake, evidence of liver disease, and laboratory findings. Abstinence is the most important treatment for ALD and the treatment plan varies according to the stage of the disease. Various treatments including abstinence, nutritional therapy, pharmacological therapy, psychotherapy, and surgery are currently available. For severe alcoholic hepatitis, corticosteroid or pentoxifylline are recommended based on the guidelines. In addition, new therapeutic targets are being under investigation. PMID:25278689

  12. Intervention with a caspase-1 inhibitor reduces obesity-associated hyperinsulinemia, non-alcoholic steatohepatitis and hepatic fibrosis in LDLR−/−.Leiden mice

    PubMed Central

    Morrison, M C; Mulder, P; Salic, K; Verheij, J; Liang, W; van Duyvenvoorde, W; Menke, A; Kooistra, T; Kleemann, R; Wielinga, P Y

    2016-01-01

    Background/Objectives: Non-alcoholic steatohepatitis (NASH) is a serious liver condition, closely associated with obesity and insulin resistance. Recent studies have suggested an important role for inflammasome/caspase-1 in the development of NASH, but the potential therapeutic value of caspase-1 inhibition remains unclear. Therefore, we aimed to investigate the effects of caspase-1 inhibition in the ongoing disease process, to mimic the clinical setting. Subjects/Methods: To investigate effects of caspase-1 inhibition under therapeutic conditions, male LDLR−/−.Leiden mice were fed a high-fat diet (HFD) for 9 weeks to induce a pre-diabetic state before start of treatment. Mice were then continued on HFD for another 12 weeks, without (HFD) or with (HFD-YVAD) treatment with the caspase-1 inhibitor Ac-YVAD-cmk (40 mg kg−1 per day). Results: Nine weeks of HFD feeding resulted in an obese phenotype, with obesity-associated hypertriglyceridemia, hypercholesterolemia, hyperglycemia and hyperinsulinemia. Treatment with Ac-YVAD-cmk did not affect further body weight gain or dyslipidemia, but did attenuate further progression of insulin resistance. Histopathological analysis of livers clearly demonstrated prevention of NASH development in HFD-YVAD mice: livers were less steatotic and neutrophil infiltration was strongly reduced. In addition, caspase-1 inhibition had a profound effect on hepatic fibrosis, as assessed by histological quantification of collagen staining and gene expression analysis of fibrosis-associated genes Col1a1, Acta2 and Tnfa. Conclusions: Intervention with a caspase-1 inhibitor attenuated the development of NASH, liver fibrosis and insulin resistance. Our data support the importance of inflammasome/caspase-1 in the development of NASH and demonstrate that therapeutic intervention in the already ongoing disease process is feasible. PMID:27121255

  13. Portal Vein Embolization with Radiolabeled Polyvinyl Alcohol Particles in a Swine Model: Hepatic Distribution and Implications for Pancreatic Islet Cell Transplantation

    SciTech Connect

    Owen, Richard J.; Mercer, John R.; Al-Saif, Faisal; Molinari, Michele; Ashforth, Robert A.; Rajotte, Ray V.; Conner-Spady, Barbara; Shapiro, A. M. James

    2009-05-15

    The distribution of radiolabeled polyvinyl alcohol microspheres (PVAMs) when infused into the portal vein of domestic swine was investigated, with the purpose of assessing implications for pancreatic islet cell transplantation. PVAMs measuring 100-300 {mu}m (Contour SE) and labeled with {sup 99m}Tc were infused into the main portal vein of 12 swine, with intermittent portal venous pressure measurements. The infusion catheter was introduced antegradely via direct or indirect cannulation of the portal vein. The liver was subsequently divided into anatomical segments. Radioactivity (decay corrected) was measured for {sup 99m}Tc microsphere synthesis, dose preparation, gross organ activities, tissue samples, and blood. Particulate labeling, catheter positioning, and infusion were successful in all cases. The number of particles used was (185,000 {+-} 24,000) with a volume of 1 ml. Mean portal pressure at 5 min was significantly higher than baseline, but without a significant difference at 15 min. Extrahepatic tissue and serum radioactivity was negligible. A significant difference in number of radioactive particles per gram was detected between segments 6/7 and segments 5/8. Intrasegmental activity was analyzed, and for segments 2/3 a significant difference in the percentage dose per gram across samples was demonstrated (P = 0.001). Effective and stable radiolabeling of PVAMs with {sup 99m}Tc-sulfur colloid was demonstrated. Portal venous infusion of 100- to 300-{mu}m particles showed entrapment in the sinusoidal hepatic system with transient portal pressure elevation. Preferential embolization into the right lateral and posterior segments occurs, suggesting that flow dynamics/catheter tip position plays a role in particle distribution.

  14. Pathological characterization and morphometric analysis of hepatic lesions in SHRSP5/Dmcr, an experimental non-alcoholic steatohepatitis model, induced by high-fat and high-cholesterol diet.

    PubMed

    Horai, Yasushi; Utsumi, Hiroyuki; Ono, Yuko; Kishimoto, Toshimitsu; Ono, Yuuichi; Fukunari, Atsushi

    2016-02-01

    SHRSP5/Dmcr is a newly established substrain of stroke-prone spontaneously hypertensive rat (SHRSP). Recently, high-fat and high-cholesterol (HFC) diet-fed SHRSP5/Dmcr has been reported as a novel rat model of developing hepatic lesions similar to human non-alcoholic steatohepatitis (NASH). The aim of this study was to investigate the detailed pathological conditions induced by HFC diet in SHRSP5/Dmcr rats using molecular biological methods and morphometric analysis. SHRSP5/Dmcr rats at 6 weeks of age were fed on either HFC diet or stroke-prone (SP) diet for 2, 4, 6, 8 and 16 weeks and histopathological changes in the liver, blood chemistry and mRNA expression levels in the liver were investigated. As evidenced by the histopathological examination of the liver of the SHRSP5/Dmcr rats, hepatic steatosis and lobular inflammation were present, with gradual increasing severity from 2 weeks after the introduction of the HFC diet. Partial hepatic fibrosis was detected at 6 weeks and spread over the entire region of the liver with more severe bridging formation by 16 weeks. The degrees of NASH-like hepatic lesions such as steatosis (the size distribution of lipid droplets), inflammation and fibrosis were quantified by morphometric analysis. Eosinophilic inclusion bodies encountered in the hepatocytes had immunoreactivity with Cox-4 and double-membrane walls, identified as mega-mitochondria. Serum ALT and bilirubins, and the mRNA expression levels related to fibrosis were closely correlated with hepatic histopathological changes. The clear feeding time-dependent progression of NASH-like hepatic lesion in HFC diet-fed SHRSP5/Dmcr rats reinforced the conclusion that this strain might be a useful model of NASH and of inflammatory fibrotic liver disease. PMID:27037502

  15. Alcoholism and Alcohol Abuse

    MedlinePlus

    ... This means that their drinking causes distress and harm. It includes alcoholism and alcohol abuse. Alcoholism, or ... brain, and other organs. Drinking during pregnancy can harm your baby. Alcohol also increases the risk of ...

  16. Alcoholic and non-alcoholic steatohepatitis

    PubMed Central

    Neuman, Manuela G.; French, Samuel W.; French, Barbara A.; Seitz, Helmut K.; Cohen, Lawrence B.; Mueller, Sebastian; Osna, Natalia A.; Kharbanda, Kusum K.; Seth, Devanshi; Bautista, Abraham; Thompson, Kyle J.; McKillop, Iain H.; Kirpich, Irina A.; McClain, Craig J.; Bataller, Ramon; Nanau, Radu M.; Voiculescu, Mihai; Opris, Mihai; Shen, Hong; Tillman, Brittany; Li, Jun; Liu, Hui; Thomas, Paul G.; Ganesan, Murali; Malnick, Steve

    2015-01-01

    This paper is based upon the “Charles Lieber Satellite Symposia” organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its comorbidities with chronic viral hepatitis in the presence or absence of human deficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible

  17. AhR signalling and dioxin toxicity.

    PubMed

    Sorg, Olivier

    2014-10-15

    Dioxins are a family of molecules associated to several industrial accidents such as Ludwigshafen in 1953 or Seveso in 1976, to the Agent Orange used during the war of Vietnam, and more recently to the poisoning of the former president of Ukraine, Victor Yushchenko. These persistent organic pollutants are by-products of industrial activity and bind to an intracellular receptor, AhR, with a high potency. In humans, exposure to dioxins, in particular 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces a cutaneous syndrome known as chloracne, consisting in the development of many small skin lesions (hamartoma), lasting for 2-5 years. Although TCDD has been classified by the WHO as a human carcinogen, its carcinogenic potential to humans is not clearly demonstrated. It was first believed that AhR activation accounted for most, if not all, biological properties of dioxins. However, certain AhR agonists found in vegetables do not induce chloracne, and other chemicals, in particular certain therapeutic agents, may induce a chloracne-like syndrome without activating AhR. It is time to rethink the mechanism of dioxin toxicity and analyse in more details the biological events following exposure to these compounds and other AhR agonists, some of which have a very different chemical structure than TCDD. In particular various food-containing AhR agonists are non-toxic and may on the contrary have beneficial properties to human health. PMID:24239782

  18. Therapy for alcoholic liver disease

    PubMed Central

    Jaurigue, Maryconi M; Cappell, Mitchell S

    2014-01-01

    Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic liver disease (ALD). ALD includes alcoholic steatosis, alcoholic hepatitis, and alcoholic cirrhosis, in order of increasing severity. Important scoring systems of ALD severity include: Child-Pugh, a semi-quantitative scoring system useful to roughly characterize clinical severity; model for end-stage liver disease, a quantitative, objective scoring system used for prognostication and prioritization for liver transplantation; and discriminant function, used to determine whether to administer corticosteroids for alcoholic hepatitis. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including twelve-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Disulfiram decreases alcohol consumption by causing unpleasant sensations after drinking alcohol from accumulation of acetaldehyde in serum, but disulfiram can be hepatotoxic. Adjunctive pharmacotherapies to reduce alcohol consumption include naltrexone, acamprosate, and baclofen. Nutritional therapy helps reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. Although reduced protein intake was previously recommended for advanced ALD to prevent hepatic encephalopathy, a diet containing 1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting. Corticosteroids are first-line therapy for severe alcoholic hepatitis (discriminant function ≥ 32), but proof of their efficacy in decreasing mortality remains elusive. Pentoxifylline is an alternative therapy. Complications of advanced ALD include ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and

  19. Nimesulide, a cyclooxygenase-2 selective inhibitor, suppresses obesity-related non-alcoholic fatty liver disease and hepatic insulin resistance through the regulation of peroxisome proliferator-activated receptor γ

    PubMed Central

    Tsujimoto, Shunsuke; Kishina, Manabu; Koda, Masahiko; Yamamoto, Yasutaka; Tanaka, Kohei; Harada, Yusuke; Yoshida, Akio; Hisatome, Ichiro

    2016-01-01

    Cyclooxygenase (COX)-2 selective inhibitors suppress non-alcoholic fatty liver disease (NAFLD); however, the precise mechanism of action remains unknown. The aim of this study was to examine how the COX-2 selective inhibitor nimesulide suppresses NAFLD in a murine model of high-fat diet (HFD)-induced obesity. Mice were fed either a normal chow diet (NC), an HFD, or HFD plus nimesulide (HFD-nime) for 12 weeks. Body weight, hepatic COX-2 mRNA expression and triglyceride accumulation were significantly increased in the HFD group. Triglyceride accumulation was suppressed in the HFD-nime group. The mRNA expression of hepatic peroxisome proliferator-activated receptor γ (PPARγ) and the natural PPARγ agonist 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) were significantly increased in the HFD group and significantly suppressed in the HFD-nime group. Glucose metabolism was impaired in the HFD group compared with the NC group, and it was significantly improved in the HFD-nime group. In addition, the plasma insulin levels in the HFD group were increased compared with those in the NC group, and were decreased in the HFD-nime group. These results indicate that HFD-induced NAFLD is mediated by the increased hepatic expression of COX-2. We suggest that the production of 15d-PGJ2, which is mediated by COX-2, induces NAFLD and hepatic insulin resistance by activating PPARγ. Furthermore, the mRNA expression of tissue inhibitor of metalloproteinases-1 (TIMP-1), procollagen-1 and monocyte chemoattractant protein-1 (MCP-1), as well as the number of F4/80-positive hepatic (Kupffer) cells, were significantly increased in the HFD group compared with the NC group, and they were reduced by nimesulide. In conclusion, COX-2 may emerge as a molecular target for preventing the development of NAFLD and insulin resistance in diet-related obesity. PMID:27431935

  20. Viral Hepatitis

    MedlinePlus

    ... Public Home » For Veterans and the Public Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... the Public Veterans and Public Home How is Hepatitis C Treated? Find the facts about the newest ...

  1. Viral Hepatitis

    MedlinePlus

    ... with hepatitis? How does a pregnant woman pass hepatitis B virus to her baby? If I have hepatitis B, what does my baby need so that she ... Can I breastfeed my baby if I have hepatitis B? More information on viral hepatitis What is hepatitis? ...

  2. Integration of Genome-Wide Computation DRE Search, AhR ChIP-chip and Gene Expression Analyses of TCDD-Elicited Responses in the Mouse Liver

    PubMed Central

    2011-01-01

    Background The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor (TF) that mediates responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Integration of TCDD-induced genome-wide AhR enrichment, differential gene expression and computational dioxin response element (DRE) analyses further elucidate the hepatic AhR regulatory network. Results Global ChIP-chip and gene expression analyses were performed on hepatic tissue from immature ovariectomized mice orally gavaged with 30 μg/kg TCDD. ChIP-chip analysis identified 14,446 and 974 AhR enriched regions (1% false discovery rate) at 2 and 24 hrs, respectively. Enrichment density was greatest in the proximal promoter, and more specifically, within ± 1.5 kb of a transcriptional start site (TSS). AhR enrichment also occurred distal to a TSS (e.g. intergenic DNA and 3' UTR), extending the potential gene expression regulatory roles of the AhR. Although TF binding site analyses identified over-represented DRE sequences within enriched regions, approximately 50% of all AhR enriched regions lacked a DRE core (5'-GCGTG-3'). Microarray analysis identified 1,896 number of TCDD-responsive genes (|fold change| ≥ 1.5, P1(t) > 0.999). Integrating this gene expression data with our ChIP-chip and DRE analyses only identified 625 differentially expressed genes that involved an AhR interaction at a DRE. Functional annotation analysis of differentially regulated genes associated with AhR enrichment identified overrepresented processes related to fatty acid and lipid metabolism and transport, and xenobiotic metabolism, which are consistent with TCDD-elicited steatosis in the mouse liver. Conclusions Details of the AhR regulatory network have been expanded to include AhR-DNA interactions within intragenic and intergenic genomic regions. Moreover, the AhR can interact with DNA independent of a DRE core suggesting there are alternative mechanisms of AhR-mediated gene regulation. PMID:21762485

  3. Leflunomide Induces Pulmonary and Hepatic CYP1A Enzymes via Aryl Hydrocarbon Receptor.

    PubMed

    Patel, Ananddeep; Zhang, Shaojie; Paramahamsa, Maturu; Jiang, Weiwu; Wang, Lihua; Moorthy, Bhagavatula; Shivanna, Binoy

    2015-12-01

    Emerging evidence indicates that the aryl hydrocarbon receptor (AhR) plays a crucial role in normal physiologic homeostasis. Additionally, aberrant AhR signaling leads to several pathologic states in the lung and liver. Activation of AhR transcriptionally induces phase I (CYP1A) detoxifying enzymes. Although the effects of the classic AhR ligands such as 3-methylcholanthrene and dioxins on phase 1 enzymes are well studied in rodent lung, liver, and other organs, the toxicity profiles limit their use as therapeutic agents in humans. Hence, there is a need to identify and investigate nontoxic AhR ligands not only to understand the AhR biology but also to develop the AhR as a clinically relevant therapeutic target. Leflunomide is a Food and Drug Administration-approved drug in humans that is known to have AhR agonist activity in vitro. Whether it activates AhR and induces phase 1 enzymes in vivo is unknown. Therefore, we tested the hypothesis that leflunomide will induce pulmonary and hepatic CYP1A enzymes in C57BL/6J wild-type mice, but not in AhR-null mice. We performed real-time reverse-transcription polymerase chain reaction analyses for CYP1A1/2 mRNA expression, western blot assays for CYP1A1/2 protein expression, and ethoxyresorufinO-deethylase assay for CYP1A1 catalytic activity. Leflunomide increased CYP1A1/A2 mRNA, protein, and enzymatic activities in wild-type mice. In contrast, leflunomide failed to increase pulmonary and hepatic CYP1A enzymes in AhR-null mice. In conclusion, we provide evidence that leflunomide induces pulmonary and hepatic CYP1A enzymes via the AhR.

  4. 12 CFR Appendixes A-H to Subpart A... - Appendixes A-H to Subpart A of Part 702

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Appendixes A-H to Subpart A of Part 702 A Appendixes A-H to Subpart A of Part 702 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS PROMPT CORRECTIVE ACTION Net Worth Classification Pt. 702, Apps. Appendixes A-H...

  5. 12 CFR Appendixes A-H to Subpart A... - Appendixes A-H to Subpart A of Part 702

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 7 2014-01-01 2014-01-01 false Appendixes A-H to Subpart A of Part 702 A Appendixes A-H to Subpart A of Part 702 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS PROMPT CORRECTIVE ACTION Net Worth Classification Pt. 702, Apps. Appendixes A-H...

  6. 12 CFR Appendixes A-H to Subpart A... - Appendixes A-H to Subpart A of Part 702

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 7 2013-01-01 2013-01-01 false Appendixes A-H to Subpart A of Part 702 A Appendixes A-H to Subpart A of Part 702 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS PROMPT CORRECTIVE ACTION Net Worth Classification Pt. 702, Apps. Appendixes A-H...

  7. 12 CFR Appendixes A-H to Subpart A... - Appendixes A-H to Subpart A of Part 702

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 7 2012-01-01 2012-01-01 false Appendixes A-H to Subpart A of Part 702 A Appendixes A-H to Subpart A of Part 702 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS PROMPT CORRECTIVE ACTION Net Worth Classification Pt. 702, Apps. Appendixes A-H...

  8. 12 CFR Appendixes A-H to Subpart A... - Appendixes A-H to Subpart A of Part 702

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Appendixes A-H to Subpart A of Part 702 A Appendixes A-H to Subpart A of Part 702 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS PROMPT CORRECTIVE ACTION Net Worth Classification Pt. 702, Apps. Appendixes A-H...

  9. Alcoholism, Alcohol, and Drugs

    ERIC Educational Resources Information Center

    Rubin, Emanuel; Lieber, Charles S.

    1971-01-01

    Describes research on synergistic effects of alcohol and other drugs, particularly barbiturates. Proposes biochemical mechanisms to explain alcoholics' tolerance of other drugs when sober, and increased sensitivity when drunk. (AL)

  10. Pharmacotherapy for alcoholic patients with alcoholic liver disease

    PubMed Central

    Vuittonet, Cynthia L.; Halse, Michael; Leggio, Lorenzo; Fricchione, Samuel B.; Brickley, Michael; Haass-Koffler, Carolina L.; Tavares, Tonya; Swift, Robert M.; Kenna, George A.

    2014-01-01

    Purpose An update on pharmacotherapy for achieving and maintaining abstinence and mitigating hepatic damage in patients with alcoholic liver disease (ALD) is presented. Summary Currently there are limited pharmacotherapy options for managing ALD, which encompasses a broad spectrum of disorders ranging from steatosis and alcoholic hepatitis to fibrosis, cirrhosis, and hepatocellular cancer. Individual variation in the severity, presentation, and complex pathologenesis of ALD defines barriers to effective treatment. Scoring of disease severity using validated assessment instruments should guide treatment approaches; abstinence and proper nutrition continue to be the cornerstones of management. A literature search (through December 31, 2013) identified no reports of randomized controlled trials using Food and Drug Administration (FDA)-approved medications for the treatment of alcohol dependence in ALD-spectrum disorders. Disulfiram, acamprosate, and naltrexone (oral and intramuscular), while approved by FDA for treatment of alcohol dependence, are not currently approved for use in patients with ALD. Baclofen (also not FDA-approved for use in ALD) is the only medication available in the United States with demonstrated safety and efficacy in reducing alcoholic behavior that has been formally tested in clinical trials in patients with ALD. Pharmacotherapy of alcoholic hepatitis using glucocorticoids or pentoxifylline has shown promise, but these options are reserved for severe ALD only. Conclusion Although various treatments have been investigated for ALD in patients with alcoholism, complete abstinence from alcohol is currently the only recommended form of hepatoprotection for the entire spectrum of ALD diagnoses. PMID:25027533

  11. Ah receptor ligands in tobacco smoke.

    PubMed

    Löfroth, G; Rannug, A

    1988-08-01

    Tar particulates from cigarette smoke contain compounds with affinity for the Ah receptor. The sidestream activity is larger than that of the mainstream with a ratio of about 5. The compounds causing the affinity appear in the neutral fraction after chemical fractionation excluding basic and acidic components as major contributors to the affinity. The affinity cannot be explained by benzo[a]pyrene and other polycyclic aromatic hydrocarbons but it might be caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds and by oxidized tryptophan derivatives.

  12. Clinically important immunological processes in acute and fulminant hepatitis, mainly due to hepatitis B virus.

    PubMed Central

    Mackenjee, M K; Kiepiela, P; Cooper, R; Coovadia, H M

    1982-01-01

    Clinically useful criteria were found by studying immunological functions on admission in 15 African children with acute hepatitis (AH) (11 of whom were HBsAg positive) and in 11 children with fulminant hepatic failure (FHF) (8 of whom were HBsAg positive), and by comparing these results with normal controls. Nine of the FHF patients died. All the AH patients survived despite the development of transient liver failure in seven. There was significant diminution of components of the classical and alternative pathways of complement and total haemolytic complement in FHF compared with AH, and in both groups in comparison with controls. Cellular immunity tested by phytohaemagglutinin and HBsAg transformation of lymphocytes and leucocyte migration inhibition with HBsAg, were more impaired in FHF than AH. These indices were reduced in both groups of patients compared with controls. The most important index correlating with severity of clinical disease was C3. It was lowest in FHF, but within this group was highest in 2 patients who survived, and in AH the C3 on admission was significantly lower in patients who subsequently showed signs of transient liver failure than in those who did not. The prothrombin index was less sensitive in differentiating serious from mild illness. It is suggested that C3 levels can be helpful in monitoring patients with acute liver disease. PMID:7082040

  13. Hepatitis virus panel

    MedlinePlus

    Hepatitis A antibody test; Hepatitis B antibody test; Hepatitis C antibody test; Hepatitis D antibody test ... or past infection, or immunity to hepatitis A Hepatitis B tests: Hepatitis B surface antigen (HBsAg), you have ...

  14. Hepatitis C and HIV

    MedlinePlus

    ... Problems : Hepatitis C Subscribe Translate Text Size Print Hepatitis C What is Hepatitis? Hepatitis means inflammation of the liver. This condition ... our related pages, Hepatitis A and Hepatitis B . Hepatitis C and HIV About 25% of people living ...

  15. Hepatitis B and HIV

    MedlinePlus

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

  16. Newspapers and newspaper ink contain agonists for the ah receptor.

    PubMed

    Bohonowych, Jessica E S; Zhao, Bin; Timme-Laragy, Alicia; Jung, Dawoon; Di Giulio, Richard T; Denison, Michael S

    2008-04-01

    Ligand-dependent activation of the aryl hydrocarbon receptor (AhR) pathway leads to a diverse array of biological and toxicological effects. The best-studied ligands for the AhR include polycyclic and halogenated aromatic hydrocarbons, the most potent of which is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, as new AhR ligands are identified and characterized, their structural and physiochemical diversity continues to expand. Our identification of AhR agonists in crude extracts from diverse materials raises questions as to the magnitude and extent of human exposure to AhR ligands through normal daily activities. We have found that solvent extracts of newspapers from countries around the world stimulate the AhR signaling pathway. AhR agonist activity was observed for dimethyl sulfoxide (DMSO), ethanol, and water extracts of printed newspaper, unprinted virgin paper, and black printing ink, where activation of luciferase reporter gene expression was transient, suggesting that the AhR active chemical(s) was metabolically labile. DMSO and ethanol extracts also stimulated AhR transformation and DNA binding, and also competed with [(3)H]TCDD for binding to the AhR. In addition, DMSO extracts of printed newspaper induced cytochrome P450 1A associated 7-ethoxyresorufin-O-deethylase activity in zebrafish embryos in vivo. Although the responsible bioactive chemical(s) remain to be identified, our results demonstrate that newspapers and printing ink contain relatively potent metabolically labile agonists of the AhR. Given the large amount of recycling and reprocessing of newspapers throughout the world, release of these easily extractable AhR agonists into the environment should be examined and their potential effects on aquatic organisms assessed. PMID:18203687

  17. AH Leo and the Blazhko Effect

    NASA Astrophysics Data System (ADS)

    Phillips, J.; Gay, P. L.

    2004-12-01

    We obtained 563 V-Band observations of AH Leo between January 27 and May 12, 2004. All observations were obtained with a 12-inch Schmidt-Cassegrain located on the island of Saipan, in the Commonwealth of the Northern Mariana Islands. We show that AH Leo is a type RRab RR Lyrae star with a minimum magnitude of V=14.658 magnitudes, a maximum amplitude of 0.989 magnitudes and a minimum amplitude of perhaps just 0.4 magnitudes. Its primary period is 0.4662609 days. Our observations also confirm the presence of the Blazhko effect, which had previously been detected by Smith and Gay (private communication) in 1993 and 1994. We estimate the Blazhko period to be roughly 20-days, however poor phase coverage at maximum light makes exact determination impossible. We also note that the bump during minimum, which is common in many RR Lyraes, varied throughout the Blazhko cycle, demonstrating amplitudes between 0 and 0.15 magnitudes. We would like to thank Sarah Maddison and Swinburne Astronomy Online for supporting this project

  18. Aryl Hydrocarbon Receptor Plays Protective Roles against High Fat Diet (HFD)-induced Hepatic Steatosis and the Subsequent Lipotoxicity via Direct Transcriptional Regulation of Socs3 Gene Expression.

    PubMed

    Wada, Taira; Sunaga, Hiroshi; Miyata, Kazuki; Shirasaki, Haruno; Uchiyama, Yuki; Shimba, Shigeki

    2016-03-25

    Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor regulating the expression of genes involved in xenobiotic response. Recent studies have suggested that AhR plays essential roles not only in xenobiotic detoxification but also energy metabolism. Thus, in this study, we studied the roles of AhR in lipid metabolism. Under high fat diet (HFD) challenge, liver-specific AhR knock-out (AhR LKO) mice exhibited severe steatosis, inflammation, and injury in the liver. Gene expression analysis and biochemical study revealed thatde novolipogenesis activity was significantly increased in AhR LKO mice. In contrast, induction of suppressor of cytokine signal 3 (Socs3) expression by HFD was attenuated in the livers of AhR LKO mice. Rescue of theSocs3gene in the liver of AhR LKO mice cancelled the HFD-induced hepatic lipotoxicities. Promoter analysis established Socs3 as novel transcriptional target of AhR. These results indicated that AhR plays a protective role against HFD-induced hepatic steatosis and the subsequent lipotoxicity effects, such as inflammation, and that the mechanism of protection involves the direct transcriptional regulation ofSocs3expression by AhR. PMID:26865635

  19. Alcohol Alert

    MedlinePlus

    ... Us You are here Home » Alcohol Alert Alcohol Alert The NIAAA Alcohol Alert is a quarterly bulletin that disseminates important research ... text. To order single copies of select Alcohol Alerts, see ordering Information . To view publications in PDF ...

  20. Alcoholism - resources

    MedlinePlus

    Resources - alcoholism ... The following organizations are good resources for information on alcoholism : Alcoholics Anonymous -- www.aa.org Al-Anon/Alateen -- www.al-anon.org/home National Institute on Alcohol ...

  1. Alcoholic neuropathy

    MedlinePlus

    Neuropathy - alcoholic; Alcoholic polyneuropathy ... The exact cause of alcoholic neuropathy is unknown. It likely includes both a direct poisoning of the nerve by the alcohol and the effect of poor nutrition ...

  2. Alcohol Facts

    MedlinePlus

    ... raquo Alcohol Facts Alcohol Facts Listen Drinks like beer, malt liquor, wine, and hard liquor contain alcohol. Alcohol is the ingredient that gets you drunk. Hard liquor—such as whiskey, rum, or gin—has more ...

  3. Testing Update on 20 and 25-Ah Lithium Ion Cells

    NASA Technical Reports Server (NTRS)

    Bruce, Gregg C.; Mardikian, Pamella; Edwards, Sherri; Bugga, Kumar; Chin, Keith; Smart, Marshall; Surampudi, Subbarao

    2003-01-01

    Eagle-Picher Energy Products has worked on lithium ion batteries for approximately 8 years. During that period EPEPC developed and delivered several cell sizes on a program funded by the USAF and Canadian DND. Designs are wound cylindrical cells from 7 to 40-Ah. Most cells delivered were approximately 25-Ah due to requirements of Mars missions. Several iterations of cells were manufactured and delivered for evaluation. The first design was 20-Ah, Design I, and the second was a 25-Ah, Design II.

  4. Alcohol Alert: Genetics of Alcoholism

    MedlinePlus

    ... and Reports » Alcohol Alert » Alcohol Alert Number 84 Alcohol Alert Number 84 Print Version The Genetics of ... immune defense system. Genes Encoding Enzymes Involved in Alcohol Breakdown Some of the first genes linked to ...

  5. Performance of AEA 80 Ah Battery under GEO Profiles

    NASA Technical Reports Server (NTRS)

    Russel, N.; Curzon, D.; Ng, K.; Lee, L.; Rao, G.

    2004-01-01

    This viewgraph presentation is divided into the following sections: 1) AEA Geosynchronous Earth Orbit (GEO) Life Testing; 2) AEA/Goddard Space Flight Center (GSFC) 20 Ah Battery; 3) AEA/GSFC 80 Ah Battery; 4) Solar Dynamic Observatory (SDO) Life Test; 5) Test Results; 6) Correlation; 7) Conclusions.

  6. Protective Role of Dietary Curcumin in the Prevention of the Oxidative Stress Induced by Chronic Alcohol with respect to Hepatic Injury and Antiatherogenic Markers

    PubMed Central

    Varatharajalu, Ravi; Garige, Mamatha; Leckey, Leslie C.; Reyes-Gordillo, Karina; Shah, Ruchi; Lakshman, M. Raj

    2016-01-01

    Curcumin, an antioxidant compound found in Asian spices, was evaluated for its protective effects against ethanol-induced hepatosteatosis, liver injury, antiatherogenic markers, and antioxidant status in rats fed with Lieber-deCarli low menhaden (2.7% of total calories from ω-3 polyunsaturated fatty acids (PUFA)) and Lieber-deCarli high menhaden (13.8% of total calories from ω-3 PUFA) alcohol-liquid (5%) diets supplemented with or without curcumin (150 mg/kg/day) for 8 weeks. Treatment with curcumin protected against high ω-3 PUFA and ethanol-induced hepatosteatosis and increase in liver injury markers, alanine aminotransferase, and aspartate aminotransferase. Curcumin upregulated paraoxonase 1 (PON1) mRNA and caused significant increase in serum PON1 and homocysteine thiolactonase activities as compared to high ω-3 PUFA and ethanol group. Moreover, treatment with curcumin protected against ethanol-induced oxidative stress by increasing the antioxidant glutathione and decreasing the lipid peroxidation adduct 4-hydroxynonenal. These results strongly suggest that chronic ethanol in combination with high ω-3 PUFA exacerbated hepatosteatosis and liver injury and adversely decreases antiatherogenic markers due to increased oxidative stress and depletion of glutathione. Curcumin supplementation significantly prevented these deleterious actions of chronic ethanol and high ω-3 PUFA. Therefore, we conclude that curcumin may have therapeutic potential to protect against chronic alcohol-induced liver injury and atherosclerosis. PMID:26881029

  7. Syzygium cumini seed extract protects the liver against lipid peroxidation with concurrent amelioration of hepatic enzymes and lipid profile of alcoholic rats.

    PubMed

    Hossain, Shahdat; Chowdhury, Imrul Hasan; Basunia, Mafroz Ahmed; Nahar, Taslima; Rahaman, Asiqur; Choudhury, Bazlur Karim; Choudhuri, Shahabuddin Kabir; Mahmud, Ishtiaq; Uddin, Borhan

    2011-01-01

    The in vitro oxidative stress induced by ethanol/Fenton's reaction in rat liver homogenates decreased significantly in the presence of Syzygium cumini seed extract, suggesting the protective effect of the seed extract against the oxidative stress in liver. To corroborate the in vitro effects by an in vivo experiment, 24 rats were divided into four groups: control, S. cumini seed-extract-administered (SE), 15% ethanol-fed (Alc) and Alc+SE rats. The oral administration of the extract (400 mg/kg BW.day) for 7 weeks significantly decreased the levels of liver LPO in the Alc+SE rats, suggesting that S. cumini seed not only obstructed the in vitro free radical production and subsequent oxidative stress, but also inhibited their in vivo formation. The oral administration of extract also reduced the enzyme activities of serum gammaglutamyl transferase, glutamate oxaloacetate transaminase and glutamate pyruvate transaminase and the levels of serum creatinine and blood urea nitrogen, serum/liver triglycerides and total cholesterol of the alcoholic rats. The levels of fecal cholesterol were increased by the extract. Fatty degenerations in liver and kidney were absent with S. cumini seed extract treatment. The results suggest that S. cumini seed may be a potential therapy for alcoholics and related dysfunctions by restraining oxidative stress. PMID:22754945

  8. Induction of AhR-Mediated Gene Transcription by Coffee

    PubMed Central

    Ishikawa, Toshio; Takahashi, Satoshi; Morita, Koji; Okinaga, Hiroko; Teramoto, Tamio

    2014-01-01

    Background Aryl hydrocarbon receptor (AhR) is classically known to be activated by xenobiotics such as dioxins and polycyclic aromatic hydrocarbons (PAHs). Although it has been reported that PAHs are contained in roasted coffee beans, in general coffee beverages are not considered to be AhR activators. We tested whether exposure to coffee would activate AhR in cultured cells. Methods HepG2 cells stably expressing an AhR-responsive reporter gene were treated with coffee samples. Also, expression of CYP1A1, an endogenous AhR-responsive gene, was quantitated by RT-PCR and Western blotting in HepG2, Caco-2, and MCF-7 cells, after treatment with coffee. In order to obtain sensitive and reproducible results, all the experiments were performed with the cells placed in either phosphate-buffered saline (PBS) or pure serum, instead of routinely-used culture medium, whose intrinsic AhR-stimulating activity turned out to be so strong as to interfere with the analyses. Results All the coffee samples tested robustly stimulated AhR-mediated transcription in the reporter gene assays. Of note, to what extent coffee and other AhR agonists activated AhR was different, depending on whether the experiments were done in PBS or serum. CYP1A1 mRNA was induced by coffee, in HepG2, Caco-2, and MCF-7 cells placed in either PBS or serum. CYP1A1 protein expression, which was not detected in these cells incubated in PBS, was also increased by coffee in cells placed in serum. Conclusions By using culture medium-free experimental settings, we have shown that coffee is a strong AhR activator. Our observation may help elucidate as-yet-unrecognized effects of coffee on human health. PMID:25007155

  9. Hepatitis C: Treatment

    MedlinePlus

    ... Public Home » Hepatitis C » Hepatitis C Treatment Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... Enter ZIP code here Enter ZIP code here Hepatitis C Treatment for Veterans and the Public Treatment ...

  10. Hepatitis C and Incarceration

    MedlinePlus

    HEPATITIS C & INCARCERATION What is hepatitis? “Hepatitis” means inflammation or swelling of the liver. The liver is an important ... viral hepatitis: Hepatitis A, Hepatitis B, and Hepatitis C. They are all different from each other and ...

  11. Hepatitis A

    MedlinePlus

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

  12. Autoimmune hepatitis

    MedlinePlus

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

  13. Hepatitis D

    MedlinePlus

    ... if the hepatitis B virus is also present. Transmission Hepatitis D can be found in the blood, ... other body fluids of people who are infected. Transmission happens when infected body fluid enters another person’s ...

  14. Hepatitis C

    MedlinePlus

    ... 2014 Select a Language: Fact Sheet 507 Hepatitis C WHAT IS HEPATITIS C? HOW IS IT DIAGNOSED? ... treatment may be less likely to work. Hep C treatment is less effective for coinfected people. Cure ...

  15. Hepatitis A

    MedlinePlus

    ... Organizations ​​ (PDF, 341 KB)​​​​​ Alternate Language URL Español Hepatitis A Page Content On this page: What is ... Nutrition Points to Remember Clinical Trials What is hepatitis A? Hepatitis * A is a virus , or infection, ...

  16. Autoimmune Hepatitis

    MedlinePlus

    ... Organizations ​​ (PDF, 341 KB)​​​​​ Alternate Language URL Autoimmune Hepatitis Page Content On this page: What is autoimmune ... Points to Remember Clinical Trials What is autoimmune hepatitis? Autoimmune hepatitis is a chronic—or long lasting— ...

  17. Hepatitis C

    MedlinePlus

    ... an inflammation of the liver. One type, hepatitis C, is caused by the hepatitis C virus (HCV). It usually spreads through contact with ... childbirth. Most people who are infected with hepatitis C don't have any symptoms for years. If ...

  18. Non-alcoholic fatty liver disease.

    PubMed

    Pearce, Lynne

    2016-08-24

    Essential facts Non-alcoholic fatty liver disease (NAFLD) is an excess of fat in the liver that is not the result of excessive alcohol consumption or other secondary causes, such as hepatitis C. According to the National Institute for Health and Care Excellence, fatty liver - steatosis - affects between 20% and 30% of the population and its prevalence is increasing. PMID:27641564

  19. The Adverse Effects of Alcohol on Vitamin A Metabolism

    PubMed Central

    Clugston, Robin D.; Blaner, William S.

    2012-01-01

    The objective of this review is to explore the relationship between alcohol and the metabolism of the essential micronutrient, vitamin A; as well as the impact this interaction has on alcohol-induced disease in adults. Depleted hepatic vitamin A content has been reported in human alcoholics, an observation that has been confirmed in animal models of chronic alcohol consumption. Indeed, alcohol consumption has been associated with declines in hepatic levels of retinol (vitamin A), as well as retinyl ester and retinoic acid; collectively referred to as retinoids. Through the use of animal models, the complex interplay between alcohol metabolism and vitamin A homeostasis has been studied; the reviewed research supports the notion that chronic alcohol consumption precipitates a decline in hepatic retinoid levels through increased breakdown, as well as increased export to extra-hepatic tissues. While the precise biochemical mechanisms governing alcohol’s effect remain to be elucidated, its profound effect on hepatic retinoid status is irrefutable. In addition to a review of the literature related to studies on tissue retinoid levels and the metabolic interactions between alcohol and retinoids, the significance of altered hepatic retinoid metabolism in the context of alcoholic liver disease is also considered. PMID:22690322

  20. Diagnosis of alcoholic liver disease.

    PubMed

    Torruellas, Cara; French, Samuel W; Medici, Valentina

    2014-09-01

    Alcohol is a hepatotoxin that is commonly consumed worldwide and is associated with a spectrum of liver injury including simple steatosis or fatty liver, alcoholic hepatitis, fibrosis, and cirrhosis. Alcoholic liver disease (ALD) is a general term used to refer to this spectrum of alcohol-related liver injuries. Excessive or harmful alcohol use is ranked as one of the top five risk factors for death and disability globally and results in 2.5 million deaths and 69.4 million annual disability adjusted life years. All patients who present with clinical features of hepatitis or chronic liver disease or who have elevated serum elevated transaminase levels should be screened for an alcohol use disorder. The diagnosis of ALD can generally be made based on history, clinical and laboratory findings. However, the diagnosis of ALD can be clinically challenging as there is no single diagnostic test that confirms the diagnosis and patients may not be forthcoming about their degree of alcohol consumption. In addition, clinical findings may be absent or minimal in early ALD characterized by hepatic steatosis. Typical laboratory findings in ALD include transaminase levels with aspartate aminotransferase greater than alanine aminotransferase as well as increased mean corpuscular volume, gamma-glutamyltranspeptidase, and IgA to IgG ratio. In unclear cases, the diagnosis can be supported by imaging and liver biopsy. The histological features of ALD can ultimately define the diagnosis according to the typical presence and distribution of hepatic steatosis, inflammation, and Mallory-Denk bodies. Because of the potential reversible nature of ALD with sobriety, regular screening of the general population and early diagnosis are essential. PMID:25206273

  1. Diagnosis of alcoholic liver disease

    PubMed Central

    Torruellas, Cara; French, Samuel W; Medici, Valentina

    2014-01-01

    Alcohol is a hepatotoxin that is commonly consumed worldwide and is associated with a spectrum of liver injury including simple steatosis or fatty liver, alcoholic hepatitis, fibrosis, and cirrhosis. Alcoholic liver disease (ALD) is a general term used to refer to this spectrum of alcohol-related liver injuries. Excessive or harmful alcohol use is ranked as one of the top five risk factors for death and disability globally and results in 2.5 million deaths and 69.4 million annual disability adjusted life years. All patients who present with clinical features of hepatitis or chronic liver disease or who have elevated serum elevated transaminase levels should be screened for an alcohol use disorder. The diagnosis of ALD can generally be made based on history, clinical and laboratory findings. However, the diagnosis of ALD can be clinically challenging as there is no single diagnostic test that confirms the diagnosis and patients may not be forthcoming about their degree of alcohol consumption. In addition, clinical findings may be absent or minimal in early ALD characterized by hepatic steatosis. Typical laboratory findings in ALD include transaminase levels with aspartate aminotransferase greater than alanine aminotransferase as well as increased mean corpuscular volume, gamma-glutamyltranspeptidase, and IgA to IgG ratio. In unclear cases, the diagnosis can be supported by imaging and liver biopsy. The histological features of ALD can ultimately define the diagnosis according to the typical presence and distribution of hepatic steatosis, inflammation, and Mallory-Denk bodies. Because of the potential reversible nature of ALD with sobriety, regular screening of the general population and early diagnosis are essential. PMID:25206273

  2. Alcoholic steatohepatitis: management and prognosis.

    PubMed

    Maher, Jacquelyn J

    2007-03-01

    Alcoholic hepatitis is a disease with a wide range of severity. Patients with severe disease have short-term mortality rates above 35%. In these high-risk patients, pharmacologic therapy is an important adjunct to supportive medical care and has been proved to improve survival. Given the benefit of drug treatment, it is important to identify patients at risk of early mortality from alcoholic hepatitis. A number of validated scoring systems are useful for this purpose, including the Maddrey Discriminant Function, the Model of End-Stage Liver Disease score, and the Glasgow Alcoholic Hepatitis score. Patients judged by one or more of these criteria to have severe alcoholic hepatitis should be treated with corticosteroids or pentoxifylline, provided they have no contraindications for this treatment. Adequate nutrition is also critical and should be provided by tube feeding if necessary. A prompt decline in serum bilirubin indicates a favorable response to therapy. Patients who do not exhibit a reduction in serum bilirubin within 1 week are considered nonresponders and have a 6-month mortality rate of 50% or higher. PMID:17335676

  3. Liver Biochemistry During the Course of Influenza A/H1N1 Infection

    PubMed Central

    Seretis, Charalampos; Lagoudianakis, Emmanuel; Salemis, Nikolaos; Pappas, Apostolos; Gemenetzis, George; Seretis, Fotios; Gourgiotis, Stavros

    2013-01-01

    Despite the multi-systemic effects of influenza A/H1N1 virus, the occurrence of hepatic injury during the natural course of the infection remains a matter of debate. We performed a review of the published clinical studies which assess the above mentioned relationship, reviewing the studies published in PubMed database (English literature), using the key words “H1N1”, “influenza A” and “liver”. We excluded case reports and clinical studies that referred to pediatric and transplanted patients, pregnants and patients with known history of chronic liver diseases. From a total of 96 results, a total of 78 papers met one or more of the exclusion criteria set. Evaluating the remaining 18 published papers, 14 more were excluded as they did not provide any sufficient data, relevant to the subject of our review. Although the analysis of the remaining studies revealed the existence of conflicting results concerning the exact degree and the potential mechanisms of liver injury in H1N1 positive patients, it can be assumed that influenza A/H1N1 virus is -or at least could be- a hepatotropic virus.

  4. Myths about drinking alcohol

    MedlinePlus

    ... to. I spend a lot of time getting alcohol, drinking alcohol, or recovering from the effects of alcohol. ... Institute on Alcohol Abuse and Alcoholism. Overview of Alcohol Consumption. www.niaaa.nih.gov/alcohol-health/overview-alcohol- ...

  5. Diagnosis of Alcoholic Liver Disease: Key Foundations and New Developments.

    PubMed

    Childers, Ryan E; Ahn, Joseph

    2016-08-01

    Alcoholic liver disease is a spectrum of conditions that include alcoholic fatty liver disease, alcoholic hepatitis, and chronic alcoholic liver disease. The diagnosis of alcoholic liver disease remains founded in an accurate patient history and detailed physical examination. Concurrent with the physical examination, objective data from laboratory, imaging, and histologic studies are helpful to confirm a diagnosis of alcoholic liver disease. Novel biomarkers, scoring systems, and imaging modalities are improving the ability to diagnose and manage alcoholic liver disease, but for most practicing clinicians, these have not been adopted widely because of their cost, but also because of limitations and uncertainty in their performance characteristics. PMID:27373609

  6. Hepatitis Vaccines

    PubMed Central

    Ogholikhan, Sina; Schwarz, Kathleen B.

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

  7. [Autoimmune hepatitis].

    PubMed

    Ostojić, Rajko

    2003-01-01

    Autoimmune hepatitis is an unresolving, hepatocellular inflammation of unknown cause that is characterized by the presence of periportal hepatitis on histologic examination, tissue autoantibodies in serum, and hypergammaglobulinemia. By international consensus, the designation autoimmune hepatitis has replaced alternative terms for the condition. Three types of autoimmune hepatitis have been proposed based on immunoserologic findings. Type 1 autoimmune hepatitis is characterized by the presence of antinuclear antibodies (ANA) or smooth muscle antibodies (SMA) (or both) in serum. Seventy percent of patients with type 1 of autoimmune hepatitis are women. This type is the most common form and accounts for at least 80% of cases. Type 2 is characterized by the presence of antibodies to liver-kidney microsome type 1 (anti-LKM1) in serum. Patients with this type of autoimmune hepatitis are predominantly children. Type 3 autoimmune hepatitis is characterized by the presence of antibodies to soluble liver antigen (anti-SLA) in serum. There are no individual features that are pathognomonic of autoimmune hepatitis, and its diagnosis requires the confident exclusion of other conditions. The large majority of patients show satisfactory response to corticosteroid (usually prednisone or prednisolone) therapy. For the past 30 years it has been customary to add azathioprine as a "steroid sparing" agent to allow lower doses of steroids to be used and remission, once achieved, can be sustained in many patients with azathioprine alone after steroid withdrawal. Patients with autoimmune hepatitis who have decompensated during or after corticosteroid therapy are candidates for liver transplantation.

  8. Viral hepatitis*

    PubMed Central

    Deinhardt, F.; Gust, I. D.

    1982-01-01

    Three forms of viral hepatitis can be recognized: hepatitis A, hepatitis B, and hepatitis non-A, non-B. Hepatitis A is caused by a picornavirus, is transmitted by the faceal—oral route, does not become chronic, and no chronic virus carriers exist. The virus can be grown in cell cultures, and killed as well as live attenuated virus vaccines are under development. Hepatitis B is caused by an enveloped virus containing a circular, double-stranded form of DNA. The disease is transmitted parenterally through inoculation of blood or blood products containing virus or through close personal contact with a virus-positive person. Hepatitis B becomes chronic in a certain number of cases and can lead to cirrhosis and primary liver cell carcinoma. The blood and certain body secretions of individuals with a persistent or chronic infection may remain infectious for many years. The hepatitis B virus cannot be grown in cell cultures but the entire genome has been sequenced and cloned in bacterial and eukaryotic cells. An inactivated virus vaccine has been prepared from hepatitis B surface antigen present in the plasma of hepatitis B virus carriers and further vaccines are under development. The agents of hepatitis non-A, non-B have not been identified. It is possible to distinguish between a predominantly parenterally transmitted and an orally transmitted form of hepatitis non-A, non-B. The latter is reported to be caused by a picornavirus that does not, however, have any antigenic relationship with hepatitis A virus. PMID:6817933

  9. AH-1S communication switch integration program

    NASA Technical Reports Server (NTRS)

    Haworth, Loran; Szoboszlay, Zoltan; Shively, Robert; Bick, Frank J.

    1989-01-01

    The C-6533/ARC communication system as installed on the test AH-1E Cobra helicopter was modified to allow discrete radio selection of all aircraft radios at the cyclic radio/intercommunication system switch. The current Cobra-fleet use of the C-6533 system is cumbersome, particularly during low-altitude operations. Operationally, the current system C-6533 configuration and design requires the pilot to estimate when he can safely remove his hand from an active flight control to select radios during low-altitude flight. The pilot must then physically remove his hand from the flight control, look inside the cockpit to select and verify the radio selection and then effect the selected radio transmission by activating the radio/ICS switch on the cyclic. This condition is potentially hazardous, especially during low-level flight at night in degraded weather. To improve pilot performance, communications effectiveness, and safety, manprint principles were utilized in the selection of a design modification. The modified C-6533 design was kept as basic as possible for potential Cobra-fleet modification. The communications system was modified and the design was subsequently flight-tested by the U.S. Army Aeroflightdynamics Directorate and NASA at the NASA Ames Research Center, Mountain View, California. The design modification enables the Cobra pilot to maintain hands-on flight controls while selecting radios during nap-of-the-Earth (NOE) flight without looking inside the cockpit which resulted in reduced pilot workload ratings, better pilot handling quality ratings and increased flight safety for the NOE flight environment.

  10. Validation of AshTest as a Non-Invasive Alternative to Transjugular Liver Biopsy in Patients with Suspected Severe Acute Alcoholic Hepatitis

    PubMed Central

    Rudler, Marika; Mouri, Sarah; Charlotte, Frederic; Cluzel, Philippe; Ngo, Yen; Munteanu, Mona; Lebray, Pascal; Ratziu, Vlad; Thabut, Dominique; Poynard, Thierry

    2015-01-01

    Background/Aims According to guidelines, the histological diagnosis of severe alcoholic steatohepatitis (ASH) can require liver biopsy if a specific treatment is needed. The blood test AshTest (BioPredictive, Paris, France) has been initially validated for the non-invasive diagnosis of ASH in a large population of heavy drinkers. The aim was to validate the AshTest accuracy in the specific context of use of patients with suspected severe ASH, in order to reduce the need for transjugular biopsy before deciding treatment. Methods The reference was liver biopsy, performed using the transjugular route, classified according to its histological severity as none, minimal, moderate or severe. Biopsies were assessed by the same experienced pathologist, blinded to simultaneous AshTest results. Results A total of 123 patients with severe clinical ASH (recent jaundice and Maddrey function greater or equal to 32) were included, all had cirrhosis and 80% had EASL histological definition of ASH. 95% of patients received prednisolone; and the 2-year mortality was 63%. The high AshTest performance was confirmed both for the binary outcome [AUROC = 0.803 (95%CI 0.684–0.881)] significantly higher than the AST/ALT AUROC [0.603 (0.462–0.714); P<0.001], and for the severity of ASH-score system by the Obuchowski measures for [mean (SE) 0.902 (0.017) vs. AST/ALT 0.833 (0.023); P = 0.01], as well as for the diagnosis and severity of ballooning, PMN and Mallory bodies. According to attributability of discordances, AshTest had a 2–7% risk of 2 grades misclassification. Conclusion These results confirmed the diagnostic performance of AshTest in cirrhotic patients with severe clinical ASH, in the specific context of use of corticosteroid treatment. AshTest is an appropriate non-invasive alternative to transjugular liver biopsy. PMID:26252713

  11. Comparisons of parallel potential biomarkers of 1H-MRS-measured hepatic lipid content in patients with non-alcoholic fatty liver disease

    PubMed Central

    Shih, Kai-Lun; Su, Wei-Wen; Chang, Chia-Chu; Kor, Chew-Teng; Chou, Chen-Te; Chen, Ting-Yu; Wu, Hung-Ming

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease. This cross-sectional study aimed to evaluate whether parallel clinical features and serum markers are related to the severity of NAFLD. We enrolled 111 participants with different metabolic syndrome (MetS) scores (zero, n = 22; one, n = 19; two, n = 22; and ≥ three, n = 48) and used 1H-MRS to measure liver fat content. Biochemical profiles and potential biomarkers of NAFLD were measured in fasting plasma. We found that 1H-MRS-measured fat content was significantly associated with MetS score ≥1, endotoxin, and hs-CRP. Ordinal logistic regression analysis revealed that MetS score ≥2 and endotoxin were predictive of NAFLD (1H-MRS > 5%) and that endotoxin, hs-CRP, and malondialdehyde (MDA) were predictive of NAFLD with liver injury (1H-MRS > 9.67%). Endotoxin plus MetS score was shown to be the most accurate predictor of overall NAFLD (AUC = 0.854; (95% CI: 0.785–0.924), P < 0.001), and endotoxin plus hs-CRP and MDA was found to be predictive of NAFLD with liver injury (0.868; (0.801–0.936), P < 0.001). These results suggest that MetS score plus certain serum biomarkers with 1H-MRS findings may hold promise for developing an effective model for monitoring the severity of NAFLD. PMID:27079922

  12. Autoimmune hepatitis.

    PubMed

    Roberts, E A

    1995-01-01

    Autoimmune hepatitis can present as either acute or chronic disease in children. Clinical and laboratory features, including association with extrahepatic autoimmune syndromes and prompt response to immunosuppressive treatment, circulating autoantibodies and hypergammaglobulinemia, suggest an immune etiology. However, the disease mechanism remains uncertain. Different types of autoimmune hepatitis are defined on the basis of which autoantibodies are present: anti-smooth muscle (type 1), anti-liver/kidney microsomal (type 2), or anti-soluble liver antigen (type 3). Diseases which may be clinically similar to autoimmune hepatitis must be excluded before the diagnosis of autoimmune hepatitis is established: Wilson's disease, primary sclerosing cholangitis, chronic hepatitis B or C, and drug-induced liver disease are among the most important entities. Corticosteroids alone or with azathioprine constitute the usual treatment for autoimmune hepatitis. Although some children achieve a complete remission, or even recovery, and can stop immunosuppressive treatment, others required low-dose prednisone treatment indefinitely.

  13. The effect of constant darkness and circadian resynchronization on the recovery of alcohol hangover.

    PubMed

    Karadayian, Analía G; Lores-Arnaiz, Silvia; Cutrera, Rodolfo A

    2014-07-15

    Alcohol hangover (AH) is a particular state after binge-like drinking. AH begins when ethanol is absent in plasma and is characterized by a cluster of physical and psychological symptoms. Alcohol disrupts circadian patterns of behavioral and physiological parameters; however, the involvement of circadian clock on the recovery of AH was not explored. Our aim was to study the effect of continuous darkness and the possible involvement of the circadian clock in the recovery time of neuromuscular impairment and anxiety related-behavior due to AH. Male Swiss mice were habituated to 12:12 L:D or continuous darkness. Each group was injected i.p. either with saline (control group) or with ethanol (3.8 g/kg BW) (hangover group). Motor performance and anxiety phenotype were evaluated at a basal point (ZT0) and every 2 h up to 20 h after blood alcohol levels were close to zero (hangover onset). A third group was subjected to a phase advance during which a hangover episode was induced and behavioral tests were carried out for each group of treatment and resynchronization day. Constant darkness resulted to be in a faster recovery of both motor and anxiety impairments in AH compared with the recovery pattern observed under normal light-dark conditions. Mice suffering from a phase shift exhibited behavioral disruptions due to both AH and phase advance. Results indicated that a synchronized circadian clock is necessary for an adequate recovery of alcohol hangover symptoms.

  14. The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes

    PubMed Central

    Perry, Rachel J.; Samuel, Varman T.; Petersen, Kitt F.; Shulman, Gerald I.

    2015-01-01

    Non-alcoholic fatty liver disease and its downstream sequelae, hepatic insulin resistance and type 2 diabetes, are rapidly growing epidemics, which lead to increased morbidity and mortality rates, and soaring health-care costs. Developing interventions requires a comprehensive understanding of the mechanisms by which excess hepatic lipid develops and causes hepatic insulin resistance and type 2 diabetes. Proposed mechanisms implicate various lipid species, inflammatory signalling and other cellular modifications. Studies in mice and humans have elucidated a key role for hepatic diacylglycerol activation of protein kinase Cε in triggering hepatic insulin resistance. Therapeutic approaches based on this mechanism could alleviate the related epidemics of non-alcoholic fatty liver disease and type 2 diabetes. PMID:24899308

  15. Hepatitis B Vaccine

    MedlinePlus

    ... as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... What is hepatitis B?Hepatitis B is a serious infection that affects the liver. It is caused by the hepatitis B virus. ...

  16. Hepatitis C: Clinical Trials

    MedlinePlus

    ... and Public Home » Hepatitis C » Treatment Decisions Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... can I find out about participating in a hepatitis C clinical trial? Many trials are being conducted ...

  17. Hepatitis B

    MedlinePlus

    ... A Hepatitis B HPV (Human Papillomavirus) Influenza (Flu) Measles Meningococcal Disease Mumps Pertussis (Whooping Cough) Pneumococcal Disease Rubella (German Measles) Shingles (Herpes Zoster) Tetanus (Lockjaw) Professional Resources Adult ...

  18. Alcohol and Alcoholism.

    ERIC Educational Resources Information Center

    National Inst. of Mental Health (DHEW), Chevy Chase, MD. National Clearinghouse for Mental Health Information.

    This concise survey presents some of the highlights of modern research on drinking and alcoholism, as based on technical articles published in the scientific literature and the views expressed by leading authorities in the field. Contents include discussions about: (1) the nature and scope of the problem; (2) the chemical composition of alcoholic…

  19. Molecular Mechanisms of Alcoholic Fatty Liver

    PubMed Central

    Purohit, Vishnudutt; Gao, Bin; Song, Byoung-Joon

    2009-01-01

    Alcoholic fatty liver is a potentially pathologic condition which can progress to steatohepatitis, fibrosis, and cirrhosis if alcohol consumption is continued. Alcohol exposure may induce fatty liver by increasing NADH/NAD+ ratio, increasing sterol regulatory element-binding protein-1 (SREBP-1) activity, decreasing peroxisome proliferator-activated receptor-α (PPAR-α) activity, and increasing complement C3 hepatic levels. Alcohol may increase SREBP-1 activity by decreasing the activities of AMP-activated protein kinase and sirtuin-1. Tumor necrosis factor-α (TNF-α) produced in response to alcohol exposure may cause fatty liver by up-regulating SREBP-1 activity, whereas betaine and pioglitazone may attenuate fatty liver by down-regulating SREBP-1 activity. PPAR-α agonists have potentials to attenuate alcoholic fatty liver. Adiponectin and interleukin-6 may attenuate alcoholic fatty liver by up-regulating PPAR-α and insulin signaling pathways while down-regulating SREBP-1 activity, and suppressing TNF-α production. Recent studies show that paracrine activation of hepatic cannabinoid receptor 1 by hepatic stellate cell-derived endocannabinoids also contributes to the development of alcoholic fatty liver. Furthermore, oxidative modifications and inactivation of the enzymes involved in the mitochondrial and/or peroxisomal β-oxidation of fatty acids could contribute to fat accumulation in the liver. PMID:19032584

  20. Clinical effect of a polysaccharide-rich extract of Acanthopanax senticosus on alcohol hangover.

    PubMed

    Bang, Joon Seok; Chung, Yoon Hee; Chung, Su Jin; Lee, Ho Sung; Song, Eun Ho; Shin, Yong Kyoo; Lee, Yu Jeung; Kim, Hyoung-Chun; Nam, Yunsung; Jeong, Ji Hoon

    2015-04-01

    The present study aimed to examine the effects polysaccharide-rich extract of Acanthopanax senticosus (PEA) on blood alcohol concentration (BAC) and hangover as well as blood lab parameters. A randomized, placebo-controlled, double-blind crossover trial was conducted. The PEA was orally administered before and after consuming alcohol 1.75 g/kg of pure alcohol. After alcohol consumption, BAC was measured for evaluation of alcohol pharmacokinetics. In the second day morning, subjects were asked to complete the Acute Hangover Scale (AHS) questionnarie. BAC results showed little difference between placebo and PEA groups, indicating that PEA does not have an effect on the pharmacokinetics of alcohol. However, several AHS items (i.e., tired, headache, dizziness, stomachache and nausea) and AHS total score were significantly improved by PEA. Blood lab parameters were significantly altered by alcohol in the placebo group. The alteration by alcohol of glucose and C-reactive protein (CRP) level was significantly attenuated by PEA. Therefore, PEA may have potential to reduce the severity of the alcohol hangover by inhibiting the alcohol-induced hypoglycemia and inflammatory response. PMID:26012258

  1. Clinical effect of a polysaccharide-rich extract of Acanthopanax senticosus on alcohol hangover.

    PubMed

    Bang, Joon Seok; Chung, Yoon Hee; Chung, Su Jin; Lee, Ho Sung; Song, Eun Ho; Shin, Yong Kyoo; Lee, Yu Jeung; Kim, Hyoung-Chun; Nam, Yunsung; Jeong, Ji Hoon

    2015-04-01

    The present study aimed to examine the effects polysaccharide-rich extract of Acanthopanax senticosus (PEA) on blood alcohol concentration (BAC) and hangover as well as blood lab parameters. A randomized, placebo-controlled, double-blind crossover trial was conducted. The PEA was orally administered before and after consuming alcohol 1.75 g/kg of pure alcohol. After alcohol consumption, BAC was measured for evaluation of alcohol pharmacokinetics. In the second day morning, subjects were asked to complete the Acute Hangover Scale (AHS) questionnarie. BAC results showed little difference between placebo and PEA groups, indicating that PEA does not have an effect on the pharmacokinetics of alcohol. However, several AHS items (i.e., tired, headache, dizziness, stomachache and nausea) and AHS total score were significantly improved by PEA. Blood lab parameters were significantly altered by alcohol in the placebo group. The alteration by alcohol of glucose and C-reactive protein (CRP) level was significantly attenuated by PEA. Therefore, PEA may have potential to reduce the severity of the alcohol hangover by inhibiting the alcohol-induced hypoglycemia and inflammatory response.

  2. [Autoimmune hepatitis].

    PubMed

    Marcais, O; Larrey, D

    1994-01-01

    Acute and chronic autoimmune hepatitis are uncommon inflammatory liver diseases, mainly occurring in young women, in association with hypergammaglobulinemia and serum autoantibodies. Different types have been described: type 1 characterized by anti-smooth muscle and anti-nuclear antibodies; type 2 characterized by anti-LKM1 antibodies; type 3 characterized by anti-SLA antibodies. Other types, still not clearly defined, may exist. Autoimmune hepatitis are associated with HLA A1 B8 DR3 and HLA DR4. Without any treatment, the disease leads to cirrhosis and, uncommonly, to fulminant hepatitis. Large doses of corticosteroids usually allow to control the disease. Relapse of hepatitis is frequent after corticosteroid withdrawal. Concomitant administration of immunosuppressive agents such as azathioprine allows to reduce corticosteroid dosage and contributes to maintain the remission of the disease. Liver transplantation may be indicated in cases of severe cirrhosis or fulminant hepatitis.

  3. Alcohol use disorder

    MedlinePlus

    ... Alcohol abuse; Problem drinking; Drinking problem; Alcohol addiction; Alcoholism - alcohol use; Substance use - alcohol ... The National Institute on Alcohol Abuse and Alcoholism ... 1 drink per day Men should not drink more than 2 drinks per day

  4. Arterial Embolization of Giant Hepatic Hemangiomas

    SciTech Connect

    Giavroglou, Constantinos; Economou, Hippolete; Ioannidis, Ioannis

    2003-02-15

    Hepatic cavernous hemangiomas are usually small and asymptomatic. They are usually discovered incidentally and only a few require treatment. However, giant hemangiomas may cause symptoms,which are indications for treatment. We describe four cases of symptomatic giant hepatic hemangiomas successfully treated with transcatheter arterial embolization, performed with polyvinyl alcohol particles. There were no complications. Follow-up with clinical and imaging examinations showed disappearance of symptoms and decrease in size of lesions.

  5. Treatment of alcoholic liver disease.

    PubMed

    Barve, Ashutosh; Khan, Rehan; Marsano, Luis; Ravindra, Kadiyala V; McClain, Craig

    2008-01-01

    Alcoholic Liver Disease (ALD) is a major cause of morbidity and mortality both in the United States and worldwide. In the United States, it is projected that over 2,000,000 persons have ALD, and the mortality for cirrhosis with superimposed alcoholic hepatitis is much worse than that of many common types of cancer. Unfortunately, there is no FDA approved therapy for ALD. We have made major strides in the last decade in identifying mechanisms for the development of liver injury in ALD, and therapies are evolving directed at specific mechanisms. It is clear that life style modification with abstinence, cessation of smoking and weight loss (if overweight) are beneficial. It is also clear that most patients with advanced liver disease have some form of malnutrition, and nutritional supplementation is of benefit. Patients with alcoholic hepatitis that is relatively severe in nature, but not complicated by issues such as infection or GI bleeding, appear to benefit from steroids. A drop in bilirubin should be monitored in steroid treated patients. Pentoxifylline appears to be beneficial in patients with alcoholic hepatitis, especially those with early hepatorenal syndrome. A variety of other agents such as PTU, lecithin, colchicine, and anabolic steroids are probably not effective. Complementary and alternative medicine agents such as zinc, milk thistle, and SAM have great therapeutic rationale. Results of ongoing NIH studies evaluating agents such as specific anti-TNF's, SAM and Milk Thistle are eagerly awaited. Transplantation is clearly an option for end stage ALD in patients who are abstinent.

  6. Ah receptor mediated suppression of the antibody response in mice is primarily dependent on the Ah phenotype of lymphoid tissue.

    PubMed

    Silkworth, J B; Antrim, L A; Sack, G

    1986-12-01

    Halogenated aromatic hydrocarbons act through the aromatic hydrocarbon (Ah) receptor in mice to produce a series of toxic effects of the immune system. The receptor protein is a product of the Ah gene locus. Ah responsive (Ahb/Ahb) mice express a high affinity receptor in both lymphoid and nonlymphoid tissues whereas nonresponsive Ahd/Ahd mice express a poor affinity receptor. To determine the role of the Ah receptor of lymphoid tissue relative to that of nonlymphoid tissue in the induction of immune impairment, bone marrow was used to reconstitute lethally irradiated mice of the same or opposite Ah phenotype. All mice were given 3,3',4,4'-tetrachlorobiphenyl (35 and 350 mumol/kg) ip 2 days before immunization with sheep erythrocytes (SRBC). The immune response to this T dependent antigen and organ weights were determined 5 or 7 days later in normal or chimeric mice, respectively. Monoclonal Lyt 1.1 and Lyt 1.2 antibodies were used to establish the origin of the cells which repopulated the chimeric thymuses. The immune responses of both BALB/cBy (Ahb/Ahb) and the BALB/cBy X DBA/2 hybrid, CByD2F1 (Ahb/Ahd), were significantly suppressed but DBA/2 mice were unaffected. The immune responses of chimeric BALB/cBy----BALB/cBy and BALB/cBy----DBA/2 (donor----recipient) mice were also significantly suppressed and thymic atrophy was observed in both cases. The serum anti-SRBC antibody titers of DBA/2----BALB/cBy chimeras were also significantly decreased although not to the same extent as in BALB/cBy----DBA/2 mice. Chimeric DBA/2----DBA/2 mice were not affected. These results indicate that the sensitivity to Ah receptor mediated suppression of the antibody response is primarily determined by the Ah phenotype of the lymphoid tissue.

  7. Pathophysiological Significance of Hepatic Apoptosis

    PubMed Central

    Wang, Kewei; Lin, Bingliang

    2013-01-01

    Apoptosis is a classical pathological feature in liver diseases caused by various etiological factors such as drugs, viruses, alcohol, and cholestasis. Hepatic apoptosis and its deleterious effects exacerbate liver function as well as involvement in fibrosis/cirrhosis and carcinogenesis. An imbalance between apoptotic and antiapoptotic capabilities is a prominent characteristic of liver injury. The regulation of apoptosis and antiapoptosis can be a pivotal step in the treatment of liver diseases. PMID:27335822

  8. NOAA 26.5 Ah LEO characterization test

    NASA Technical Reports Server (NTRS)

    Morrow, G. W.

    1986-01-01

    The General Electric (GE) 26.5 Ah NOAA-G flight nickel-cadmium cells were obtained from RCA-Astro Electronics to undergo performance characterization testing at the Goddard Space Flight Center (GSFC). This lot of cells was manufactured with passivated positive plate, to control nickel structure attack duing active material impregnation, and less electrolyte than normal (less than 3cc/Ah). The cells were tested in a parametric low Earth orbit (LEO) cycling regime that was previously used to test and characterize standard 50 Ah cells. Life cycle testing at the Naval Weapons Support Center (NWSC), in Crane, followed. The results of the test showed nominal performance in comparison with previous test data on the standard 50. Life cycle testing in the NOAA orbital regime is continuing at NWSC.

  9. Design and Performance Data for 81 Ah FNC Cells

    NASA Technical Reports Server (NTRS)

    Cohen, F.; Anderman, Menahem

    1997-01-01

    Design and performance data for 81 Ah FNC cells are given. The conclusions are: that a sealed Ni-Cd cells are not limited to 50 Ah with the FNC design; energy densities of 40 Wh/kg in a conservative high Cd, high electrolyte design have been demonstrated; uniform ATP data and LEO cycling performance is being demonstrated; internal cell pressures remain low under all conditions; and no conditioning is necessary under any LEO profile; accelerated LEO cycling exhibits performance well beyond traditional space Ni-Cd cells.

  10. Hepatitis B

    MedlinePlus

    ... U.S. Preventive Services Task Force recommendation statement. Ann Intern Med . 2014;161(1):58-66. PMID 24863637 ... Development Conference Statement: Management of hepatitis B. Ann Intern Med . 2009;150:104-10. PMID: 19124811 www. ...

  11. Hepatitis B

    MedlinePlus

    ... All babies should get the vaccine, but older children and adults can get it too. If you travel to countries where Hepatitis B is common, you should get the vaccine. NIH: National Institute of Diabetes and Digestive and Kidney Diseases

  12. Hepatic Sarcoidosis.

    PubMed

    Tadros, Micheal; Forouhar, Faripour; Wu, George Y

    2013-12-01

    Sarcoidosis is a multisystem disease characterized by the presence of non-caseating granulomas in affected organs. Pulmonary involvement is the most common site of disease activity. However, hepatic involvement is also common in sarcoidosis, occurring in up to 70% of patients. Most patients with liver involvement are asymptomatic. Therefore, the majority of cases are discovered incidentally, frequently by the finding of elevated liver enzymes. Pain in the right upper quadrant of the abdomen, fatigue, pruritus, and jaundice may be associated with liver involvement. Portal hypertension and cirrhosis are complications linked to long-standing hepatic sarcoidosis. Liver biopsy is usually required to confirm the diagnosis. It is important to differentiate hepatic sarcoidosis from other autoimmune and granulomatous liver diseases. Not all cases of hepatic sarcoidosis require treatment. For symptomatic patients, the first line treatment includes corticosteroids or ursodeoxycholic acid. Various immunosuppressant agents can be used as second line agents. Rarely, severe cases require liver transplantation.

  13. Autoimmune hepatitis.

    PubMed

    Heneghan, Michael A; Yeoman, Andrew D; Verma, Sumita; Smith, Alastair D; Longhi, Maria Serena

    2013-10-26

    Autoimmune hepatitis is a disease of the hepatic parenchyma that can present in acute or chronic forms. In common with many autoimmune diseases, autoimmune hepatitis is associated with non-organ-specific antibodies in the context of hepatic autoimmunity. This dichotomy has made definition of a unifying hypothesis in the pathophysiology of the disease difficult, although data from the past 8 years have drawn attention to the role of regulatory T cells. Several triggers have been identified, and the disease arises in genetically susceptible individuals. Clinical and biochemical remission is achievable in up to 85% of cases. For the remaining patients, alternative immunosuppression strategies are an option. Liver transplantation provides an excellent outcome for patients with acute liver failure or complications of end-stage liver disease, including hepatocellular carcinoma. Variant or overlapping syndromes are worthy of consideration when unexpected disease features arise.

  14. Social class based on occupation is associated with hospitalization for A(H1N1)pdm09 infection. Comparison between hospitalized and ambulatory cases.

    PubMed

    Pujol, J; Godoy, P; Soldevila, N; Castilla, J; González-Candelas, F; Mayoral, J M; Astray, J; Garcia, S; Martin, V; Tamames, S; Delgado, M; Domínguez, A

    2016-03-01

    This study aimed to analyse the existence of an association between social class (categorized by type of occupation) and the occurrence of A(H1N1)pmd09 infection and hospitalization for two seasons (2009-2010 and 2010-2011). This multicentre study compared ambulatory A(H1N1)pmd09 confirmed cases with ambulatory controls to measure risk of infection, and with hospitalized A(H1N1)pmd09 confirmed cases to asses hospitalization risk. Study variables were: age, marital status, tobacco and alcohol use, pregnancy, chronic obstructive pulmonary disease, chronic respiratory failure, cardiovascular disease, diabetes, chronic liver disease, body mass index >40, systemic corticosteroid treatment and influenza vaccination status. Occupation was registered literally and coded into manual and non-manual worker occupational social class groups. A conditional logistic regression analysis was performed. There were 720 hospitalized cases, 996 ambulatory cases and 1062 ambulatory controls included in the study. No relationship between occupational social class and A(H1N1)pmd09 infection was found [adjusted odds ratio (aOR) 0·97, 95% confidence interval (CI) 0·74-1·27], but an association (aOR 1·53, 95% CI 1·01-2·31) between occupational class and hospitalization for A(H1N1)pmd09 was observed. Influenza vaccination was a protective factor for A(H1N1)pmd09 infection (aOR 0·41, 95% CI 0·23-0·73) but not for hospitalization. We conclude that manual workers have the highest risk of hospitalization when infected by influenza than other occupations but they do not have a different probability of being infected by influenza.

  15. Hepatitis C FAQs

    MedlinePlus

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

  16. Hepatitis B FAQs

    MedlinePlus

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

  17. Hepatitis A Test

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Hepatitis A Testing Share this page: Was this page ... HAV-Ab total; Anti-HAV Formal name: Viral Hepatitis A Antibody Related tests: Hepatitis B Testing ; Hepatitis ...

  18. Delta agent (Hepatitis D)

    MedlinePlus

    Hepatitis D virus ... Hepatitis D virus (HDV) is found only in people who carry the hepatitis B virus. HDV may make liver ... B virus but who never had symptoms. Hepatitis D infects about 15 million people worldwide. It occurs ...

  19. CCD Photometric Study and Period Investigation of AH Tauri

    NASA Astrophysics Data System (ADS)

    Xiang, Fu-Yuan; Xiao, Ting-Yu; Yu, Yun-Xia

    2015-07-01

    In this paper, we present new CCD photometric observations of AH Tauri in the R band observed in 2006 at the Yunnan Observatory. Two new times of light minima were derived from these observations. We modeled the light curves using the 2003 version of the Wilson-Devinney program. The results show that the variations of the light curves can be expained by a cool spot on the primary star. The fill-out factor is about 6.6%, indicating that AH Tauri is a shallow-contact system. The mass ratio was determined to be about 0.505. In addition, the orbital period variations of AH Tauri were investigated based on all of the photoelectric and CCD light minimum times, including our two new data. It was found that the orbital period exhibits a possible periodic variation with a period of {P}{mod}=54.62\\(+/- 0.20) years and a secular period decrease of {dP}/{dt}=-(1.823+/- 0.215)× {10}-7 {days} {{yr}}-1. Since AH Tauri is an overcontact solar-like system, we discuss three mechanisms of the mass transfer, the light-time effect of the third body, and magnetic activity responsible for the orbital period changes.

  20. PESTICIDE TRADE NAMES AND THEIR ACTIVE INGREDIENTS IN THE AHS

    EPA Science Inventory

    The detailed information on the use of specific pesticides is a major strength of exposure assessment conducted for the Agricultural Health Study (AHS). During the enrollment interviews, a check list was used to collect information on the frequency and duration of use for 28 p...

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

    MedlinePlus

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

  2. Overview of Alcohol Consumption

    MedlinePlus

    ... Search Alcohol & Your Health Overview of Alcohol Consumption Alcohol's Effects on the Body Alcohol Use Disorder Fetal Alcohol ... other questions about alcohol. Here’s what we know: Alcohol’s effects vary from person to person, depending on a ...

  3. Alcohol and pregnancy

    MedlinePlus

    Drinking alcohol during pregnancy; Fetal alcohol syndrome - pregnancy; FAS - fetal alcohol syndrome ... When a pregnant woman drinks alcohol, the alcohol travels through her blood and into the baby's blood, tissues, and organs. Alcohol breaks down much more slowly in ...

  4. Ethnic Differences in Presentation and Severity of Alcoholic Liver Disease

    PubMed Central

    Durbin-Johnson, Blythe; Halsted, Charles H.; Medici, Valentina

    2015-01-01

    Background The frequency of alcoholic liver disease (ALD), including alcoholic steatosis, hepatitis and cirrhosis, varies significantly by ethnicity. Methods With the goal to assess the role of ethnicity in determining the age of onset and severity of ALD and to compare the risk factors for its progression among ethnic groups, we conducted a retrospective chart review of all patients with ALD who were admitted or were followed as outpatients at University of California Davis Medical Center between 2002 and 2010. After excluding HBsAg and HIV positive subjects, we reviewed the charts of 791 ALD patients including 130 with alcoholic fatty liver, 154 with alcoholic hepatitis, and 507 with alcoholic cirrhosis. Results When controlling for all variables in the model, Hispanic patients presented at significantly 4-10 years younger ages than White/Caucasian patients, in each of the three disease severity categories and the results were confirmed after excluding HCV Ab/RNA positive subjects. There were more obese Hispanic patients than White/Caucasian patients, whereas the proportion of patients with hepatitis C was significantly greater in African/American subjects with alcoholic hepatitis and the proportion of patients with diabetes mellitus was significantly lower in White/Caucasian subjects than in Hispanic subjects with cirrhosis. The proportion of subjects with severe alcoholic hepatitis was similar in Hispanic and White/Caucasian patients, but lower in African/American subjects. Conclusion Ethnicity is a major factor affecting the age and severity of presentation of different subtypes of ALD. PMID:25702770

  5. Impact of Dyrk1A level on alcohol metabolism.

    PubMed

    Renon, Marjorie; Legrand, Béatrice; Blanc, Etienne; Daubigney, Fabrice; Bokobza, Cindy; Mortreux, Marie; Paul, Jean-Louis; Delabar, Jean-Maurice; Rouach, Hélène; Andreau, Karine; Janel, Nathalie

    2016-09-01

    Alcoholic liver diseases arise from complex phenotypes involving many genetic factors. It is quite common to find hyperhomocysteinemia in chronic alcoholic liver diseases, mainly due to deregulation of hepatic homocysteine metabolism. Dyrk1A, involved in homocysteine metabolism at different crossroads, is decreased in liver of hyperhomocysteinemic mice. Here, we hypothesized that Dyrk1A contributes to alcohol-induced hepatic impairment in mice. Control, hyperhomocysteinemic and mice overexpressing Dyrk1A were fed using a Lieber-DeCarli liquid diet with or without ethanol (5% v/v ethanol) for one month, and liver histological examination and liver biochemical function tests were performed. Plasma alanine aminotransferase and homocysteine levels were significantly decreased in mice overexpressing Dyrk1A compared to control mice with or without alcohol administration. On the contrary, the mean plasma alanine aminotransferase and homocysteine levels were significantly higher in hyperhomocysteinemic mice than that of control mice after alcohol administration. Paraoxonase 1 and CYP2E1, two phase I xenobiotic metabolizing enzymes, were found increased in the three groups of mice after alcohol administration. However, NQO1, a phase II enzyme, was only found increased in hyperhomocysteinemic mice after alcohol exposure, suggesting a greater effect of alcohol in liver of hyperhomocysteinemic mice. We observed positive correlations between hepatic alcohol dehydrogenase activity, Dyrk1A and ADH4 protein levels. Importantly, a deleterious effect of alcohol consumption on hepatic Dyrk1A protein level was found. Our study reveals on the one hand a role of Dyrk1A in ethanol metabolism and on the other hand a deleterious effect of alcohol administration on hepatic Dyrk1A level.

  6. Impact of Dyrk1A level on alcohol metabolism.

    PubMed

    Renon, Marjorie; Legrand, Béatrice; Blanc, Etienne; Daubigney, Fabrice; Bokobza, Cindy; Mortreux, Marie; Paul, Jean-Louis; Delabar, Jean-Maurice; Rouach, Hélène; Andreau, Karine; Janel, Nathalie

    2016-09-01

    Alcoholic liver diseases arise from complex phenotypes involving many genetic factors. It is quite common to find hyperhomocysteinemia in chronic alcoholic liver diseases, mainly due to deregulation of hepatic homocysteine metabolism. Dyrk1A, involved in homocysteine metabolism at different crossroads, is decreased in liver of hyperhomocysteinemic mice. Here, we hypothesized that Dyrk1A contributes to alcohol-induced hepatic impairment in mice. Control, hyperhomocysteinemic and mice overexpressing Dyrk1A were fed using a Lieber-DeCarli liquid diet with or without ethanol (5% v/v ethanol) for one month, and liver histological examination and liver biochemical function tests were performed. Plasma alanine aminotransferase and homocysteine levels were significantly decreased in mice overexpressing Dyrk1A compared to control mice with or without alcohol administration. On the contrary, the mean plasma alanine aminotransferase and homocysteine levels were significantly higher in hyperhomocysteinemic mice than that of control mice after alcohol administration. Paraoxonase 1 and CYP2E1, two phase I xenobiotic metabolizing enzymes, were found increased in the three groups of mice after alcohol administration. However, NQO1, a phase II enzyme, was only found increased in hyperhomocysteinemic mice after alcohol exposure, suggesting a greater effect of alcohol in liver of hyperhomocysteinemic mice. We observed positive correlations between hepatic alcohol dehydrogenase activity, Dyrk1A and ADH4 protein levels. Importantly, a deleterious effect of alcohol consumption on hepatic Dyrk1A protein level was found. Our study reveals on the one hand a role of Dyrk1A in ethanol metabolism and on the other hand a deleterious effect of alcohol administration on hepatic Dyrk1A level. PMID:27216978

  7. Hepatitis C: Sex and Sexuality

    MedlinePlus

    ... with Hepatitis » Sex and Sexuality: Entire Lesson Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... hepatitis C virus through sex. Can you pass hepatitis C to a sex partner? Yes, but it ...

  8. Hepatitis C

    PubMed Central

    Mehta, Bharti; Kumar Dharma, Vijay; Chawla, Sumit; Jindal, Harashish; Bhatt, Bhumika

    2014-01-01

    Hepatitis C Virus (HCV) infection is a major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Following acute infection, 20% of people eliminate the virus over weeks or months and are often asymptomatic. The remaining 80% of people will develop chronic disease, of which approximately 20% will eventually develop liver cirrhosis and 1–5% will develop liver cancer. About 150 million people are chronically infected with HCV, and more than 350 000 people die every year from hepatitis C related liver diseases. The economic cost of hepatitis C is significant both to the individual and to the society. In the United States the average lifetime cost of the disease was estimated at $33 407 USD with the cost of a liver transplant approximately $200 000 USD. PEG-IFN and ribavirin treatment is also expensive and, at an average cost of approximately GB £7000 in the UK for a treatment course, is unaffordable in developing countries. Hepatitis C, not only brings down the quality of the life of individuals but also affect progress of the nation by adding financial burden. If we prevent the disease from occurring or find a perfect cure of the disease, in form of a prophylactic or therapeutic vaccine, it will be a boon to not only to the individual but to the nation as a whole. PMID:24165512

  9. Hepatic encephalopathy.

    PubMed

    Córdoba, Juan; Mínguez, Beatriz

    2008-02-01

    Hepatic encephalopathy is a severe complication of cirrhosis that is related to the effects of ammonia. Analysis of interorgan ammonia trafficking has identified an important role of skeletal muscle in ammonia removal and has highlighted the importance of the nutritional status. Ammonia causes neurotransmitter abnormalities and induces injury to astrocytes that is partially mediated by oxidative stress. These disturbances lead to astrocyte swelling and brain edema, which appear to be involved in the pathogenesis of neurological manifestations. Inflammatory mediators worsen brain disturbances. New methods for assessing hepatic encephalopathy include clinical scales, neuropsychological tests, imaging of portal-systemic circulation, and magnetic resonance of the brain. Reappraisal of current therapy indicates the need for performing placebo-controlled trials and the lack of evidence for administering diets with restricted protein content. Liver transplant should be considered in selected patients with hepatic encephalopathy. Future prospects include new drugs that decrease plasma ammonia, measures to reduce brain edema, and liver-support devices. PMID:18293278

  10. Hepatic sarcoidosis.

    PubMed

    Karagiannidis, Alexandros; Karavalaki, Maria; Koulaouzidis, Anastasios

    2006-01-01

    Sarcoidosis is a multisystem disease of unknown aetiology. Histological evidence of non-caseating granulomas represents the main finding. It affects mostly young people, targeting primary the lung and hilar lymph nodes although liver involvement is often encountered. Hepatic sarcoidosis covers a broad spectrum from asymptomatic hepatic granulomas formation and slightly deranged liver function tests to clinically evident disease with cholestasis or, in advanced cases, cirrhosis and portal hypertension. Other granulomatous diseases (mainly systemic infections like tuberculosis) should be excluded prior to treatment, as longstanding corticosteroid administration is the main stem of therapy. In advanced cases, liver transplantation represents the ultimate therapeutic option.

  11. Comparing introduction to Europe of highly pathogenic avian influenza viruses A(H5N8) in 2014 and A(H5N1) in 2005.

    PubMed

    Adlhoch, C; Gossner, C; Koch, G; Brown, I; Bouwstra, R; Verdonck, F; Penttinen, P; Harder, T

    2014-01-01

    Since the beginning of November 2014, nine outbreaks of highly pathogenic avian influenza virus (HPAIV) A(H5N8) in poultry have been detected in four European countries. In this report, similarities and differences between the modes of introduction of HPAIV A(H5N1) and A(H5N8) into Europe are described. Experiences from outbreaks of A(H5N1) in Europe demonstrated that early detection to control HPAIV in poultry has proven pivotal to minimise the risk of zoonotic transmission and prevention of human cases.

  12. The physiological role of liver alcohol dehydrogenase.

    PubMed

    Krebs, H A; Perkins, J R

    1970-07-01

    1. Yeast alcohol dehydrogenase was used to determine ethanol in the portal and hepatic veins and in the contents of the alimentary canal of rats given a diet free from ethanol. Measurable amounts of a substance behaving like ethanol were found. Its rate of interaction with yeast alcohol dehydrogenase and its volatility indicate that the substance measured was in fact ethanol. 2. The mean alcohol concentration in the portal blood of normal rats was 0.045mm. In the hepatic vein, inferior vena cava and aorta it was about 15 times lower. 3. The contents of all sections of the alimentary canal contained measurable amounts of ethanol. The highest values (average 3.7mm) were found in the stomach. 4. Infusion of pyrazole (an inhibitor of alcohol dehydrogenase) raised the alcohol concentration in the portal vein 10-fold and almost removed the difference between portal and hepatic venous blood. 5. Addition of antibiotics to the food diminished the ethanol concentration of the portal blood to less than one-quarter and that of the stomach contents to less than one-fortieth. 6. The concentration of alcohol in the alimentary canal and in the portal blood of germ-free rats was much decreased, to less than one-tenth in the alimentary canal and to one-third in the portal blood, but detectable quantities remained. These are likely to arise from acetaldehyde formed by the normal pathways of degradation of threonine, deoxyribose phosphate and beta-alanine. 7. The results indicate that significant amounts of alcohol are normally formed in the gastro-intestinal tract. The alcohol is absorbed into the circulation and almost quantitatively removed by the liver. Thus the function, or a major function, of liver alcohol dehydrogenase is the detoxication of ethanol normally present. 8. The alcohol concentration in the stomach of alloxan-diabetic rats was increased about 8-fold. 9. The activity of liver alcohol dehydrogenase is generally lower in carnivores than in herbivores and omnivores

  13. An orbital period for the dwarf nova AH Herculis

    NASA Astrophysics Data System (ADS)

    Moffat, A. F. J.; Shara, M. M.

    1984-07-01

    AH Her is the best-studied dwarf nova which displays rapid coherent oscillations at maximum light, yet its orbital period is not determined. Eleven nights of observations with the 1-meter Wise Observatory telescope with chopping secondary, and 'Nather' photometer, yield a period P = 0.247 + or - 0.008 day, in excellent agreement with that predicted from the decline rate of the outburst. The source of flickering in the system (presumably the hot spot) is shown to fluctuate with the same amplitude whether AH Her is in outburst or not. The implication is that the accretion stream, hot spot, and outer disk are unaffected by, and do not take part in the eruption.

  14. Hepatitis C.

    PubMed

    Liddle, C

    1996-04-01

    The hepatitis C virus (HCV) genome was isolated during the late 1980s using molecular cloning techniques. It is recognized as the cause of most cases of percutaneously transmitted non-A, non-B hepatitis. Prevalence of antibodies to HCV(anti-HCV) in the general Australian population is 0.3%. However, among regular intravenous drug users the prevalence exceeds 90%. The predominant risk factors for HCV are intravenous drug use, tattoos, exposure to blood products, occupational risk and ethnicity. In contrast to hepatitis B, sexual spread and vertical transmission of HCV from mother to neonate are relatively uncommon. The risk of acquiring HCV from a single HCV-contaminated needlestick accident is about 5%. Most cases of acute HCV infection are asymptomatic, but 50 to 80% progress to chronic disease. The percentage of those with chronic HCV progressing to cirrhosis is not accurately known, but is probably 20%. Treatment strategies for HCV, utilizing recombinant interferons, are proving useful in patients with mild to moderate liver disease, but fare less well in patients with cirrhosis. Currently, there is no vaccine for hepatitis C, so pre-exposure prophylaxis is not possible. Equally, no post-exposure intervention, for example with gamma globulin, has been shown to be beneficial, though there may be a role for early interferon therapy.

  15. The effects of Nigella sativa (Ns), Anthemis hyalina (Ah) and Citrus sinensis (Cs) extracts on the replication of coronavirus and the expression of TRP genes family.

    PubMed

    Ulasli, Mustafa; Gurses, Serdar A; Bayraktar, Recep; Yumrutas, Onder; Oztuzcu, Serdar; Igci, Mehri; Igci, Yusuf Ziya; Cakmak, Ecir Ali; Arslan, Ahmet

    2014-03-01

    Extracts of Anthemis hyalina (Ah), Nigella sativa (Ns) and peels of Citrus sinensis (Cs) have been used as folk medicine to fight antimicrobial diseases. To evaluate the effect of extracts of Ah, Ns and Cs on the replication of coronavirus (CoV) and on the expression of TRP genes during coronavirus infection, HeLa-CEACAM1a (HeLa-epithelial carcinoembryonic antigen-related cell adhesion molecule 1a) cells were inoculated with MHV-A59 (mouse hepatitis virus-A59) at moi of 30. 1/50 dilution of the extracts was found to be the safe active dose. ELISA kits were used to detect the human IL-8 levels. Total RNA was isolated from the infected cells and cDNA was synthesized. Fluidigm Dynamic Array nanofluidic chip 96.96 was used to analyze the mRNA expression of 21 TRP genes and two control genes. Data was analyzed using the BioMark digital array software. Determinations of relative gene expression values were carried out by using the 2(-∆∆Ct) method (normalized threshold cycle (Ct) value of sample minus normalized Ct value of control). TCID50/ml (tissue culture infectious dose that will produce cytopathic effect in 50% of the inoculated tissue culture cells) was found for treatments to determine the viral loads. The inflammatory cytokine IL-8 level was found to increase for both 24 and 48 h time points following Ns extract treatment. TRPA1, TRPC4, TRPM6, TRPM7, TRPM8 and TRPV4 were the genes which expression levels changed significantly after Ah, Ns or Cs extract treatments. The virus load decreased when any of the Ah, Ns or Cs extracts was added to the CoV infected cells with Ah extract treatment leading to undetectable virus load for both 6 and 8 hpi. Although all the extract treatments had an effect on IL-8 secretion, TRP gene expression and virus load after CoV infection, it was the Ah extract treatment that showed the biggest difference in virus load. Therefore Ah extract is the best candidate in our hands that contains potential treatment molecule(s).

  16. Prevention of Steatosis by Hepatic JNK1

    PubMed Central

    Sabio, Guadalupe; Cavanagh-Kyros, Julie; Ko, Hwi Jin; Jung, Dae Young; Gray, Susan; Jun, John Y.; Barrett, Tamera; Mora, Alfonso; Kim, Jason K.; Davis, Roger J.

    2009-01-01

    Non-alcoholic steatosis (fatty liver) is a major cause of liver dysfunction that is associated with insulin resistance and metabolic syndrome. The cJun NH2-terminal kinase 1 (JNK1) signaling pathway is implicated in the pathogenesis of hepatic steatosis and drugs that target JNK1 may be useful for treatment of this disease. Indeed, mice with defects in JNK1 expression in adipose tissue are protected against hepatic steatosis. Here we report that mice with specific ablation of Jnk1 in hepatocytes exhibit glucose intolerance, insulin resistance, and hepatic steatosis. JNK1 therefore serves opposing actions in liver and adipose tissue to both promote and prevent hepatic steatosis. This finding has profound implications for the design of JNK1-selective drugs for the treatment of metabolic syndrome. PMID:19945406

  17. Chronic Hepatitis C.

    PubMed

    Tran, Tram T.; Martin, Paul

    2001-12-01

    Infection with hepatitis C virus (HCV) accounts for 40% of cases of chronic liver disease in the United States and is now the most common indication for liver transplantation. Estimates suggest that 4 million people (1.8%) of the American population are or have been infected with HCV. Currently, the treatment of choice for patients with chronic HCV infection is recombinant interferon alfa with ribavirin. Pegylated interferons are a promising new development, and in combination with ribavirin, they will rapidly become the standard of care. The goals of therapy are to slow disease progression, improve hepatic histology, reduce infectivity, and reduce the risk of hepatocellular carcinoma. Sustained virologic response, which generally implies the absence of viremia for 6 months or more following completion of therapy, is increasingly being regarded as a cure, with evidence of slowing or even regression of fibrosis on follow-up liver biopsy. A number of factors have been shown to be predictive of a sustained response, including viral genotype other than 1, low serum HCV RNA levels, absence of cirrhosis, younger age, female gender, and shorter duration of infection. Disease severity as assessed by liver biopsy, comorbidities, and possible contraindications to therapy should be weighed in the decision to begin treatment. Counseling patients regarding transmission, natural history, and drug and alcohol abstinence also should be included in management. Close monitoring should be done during treatment for side effects of interferon, including depression and bone marrow suppression. Hemolytic anemia is the major side effect of ribavirin. PMID:11696276

  18. Alcohol and skin disorders: with a focus on psoriasis.

    PubMed

    Kazakevich, Natalia; Moody, Megan N; Landau, Jennifer M; Goldberg, Leonard H

    2011-04-01

    Alcohol is a serious cause of morbidity and mortality in our society and is implicated in multiple health conditions, including hepatic failure, neurological damage, hematological disorders, and nutritional deficiencies, to name a few. Although alcohol induced cutaneous abnormalities can also cause significant morbidity, they tend to be overshadowed by the other disease states associated with alcohol use. In addition to the cutaneous stigmata linked to chronic alcoholic liver disease, alcohol can directly cause or exacerbate several skin conditions. In particular, alcohol misuse is implicated in the development of psoriasis and discoid eczema, as well as confers increased susceptibility to skin and systemic infections. Alcohol misuse might also exacerbate rosacea, porphyria cutanea tarda, and post adolescent acne. Herein, we review the evidence concerning the influences of alcohol in skin conditions with a focus on psoriasis.

  19. Alcohol during Pregnancy

    MedlinePlus

    ... Home > Pregnancy > Is it safe? > Alcohol during pregnancy Alcohol during pregnancy E-mail to a friend Please ... and fetal alcohol spectrum disorders. How does drinking alcohol during pregnancy affect your baby's health? Drinking alcohol ...

  20. Alcohol Energy Drinks

    MedlinePlus

    ... Home / About Addiction / Alcohol / Alcohol Energy Drinks Alcohol Energy Drinks Read 17728 times font size decrease font size increase font size Print Email Alcohol energy drinks (AEDs) or Caffeinated alcoholic beverages (CABs) are ...

  1. Natural co-infection of influenza A/H3N2 and A/H1N1pdm09 viruses resulting in a reassortant A/H3N2 virus

    PubMed Central

    Rith, Sareth; Chin, Savuth; Sar, Borann; Y, Phalla; Horm, Srey Viseth; Ly, Sovann; Buchy, Philippe; Dussart, Philippe; Horwood, Paul F.

    2015-01-01

    Background Despite annual co-circulation of different subtypes of seasonal influenza, co-infections between different viruses are rarely detected. These co-infections can result in the emergence of reassortant progeny. Study design We document the detection of an influenza co-infection, between influenza A/H3N2 with A/H1N1pdm09 viruses, which occurred in a 3 year old male in Cambodia during April 2014. Both viruses were detected in the patient at relatively high viral loads (as determined by real-time RT-PCR CT values), which is unusual for influenza co-infections. As reassortment can occur between co-infected influenza A strains we isolated plaque purified clonal viral populations from the clinical material of the patient infected with A/H3N2 and A/H1N1pdm09. Results Complete genome sequences were completed for 7 clonal viruses to determine if any reassorted viruses were generated during the influenza virus co-infection. Although most of the viral sequences were consistent with wild-type A/H3N2 or A/H1N1pdm09, one reassortant A/H3N2 virus was isolated which contained an A/H1N1pdm09 NS1 gene fragment. The reassortant virus was viable and able to infect cells, as judged by successful passage in MDCK cells, achieving a TCID50 of 104/ml at passage number two. There is no evidence that the reassortant virus was transmitted further. The co-infection occurred during a period when co-circulation of A/H3N2 and A/H1N1pdm09 was detected in Cambodia. Conclusions It is unclear how often influenza co-infections occur, but laboratories should consider influenza co-infections during routine surveillance activities. PMID:26590689

  2. Alcohol, psoriasis, liver disease, and anti-psoriasis drugs.

    PubMed

    Cassano, Nicoletta; Vestita, Michelangelo; Apruzzi, Doriana; Vena, Gino A

    2011-11-01

    Over the last years, data have been accumulating regarding a possible association between alcohol and psoriasis. While it is still unclear whether alcohol misuse represents a true risk factor or merely an epiphenomenon of the cutaneous disease, a number of studies support the role of ethanol and its metabolites as triggering factors of psoriasis. A drinking habit also appears to exacerbate a preexisting psoriasis, and the magnitude of alcohol consumption may be related to both a higher incidence and severity of psoriasis. Evidence also shows that deaths from alcohol-related causes are significantly more frequent in patients with psoriasis than in normal controls. Alcohol consumption may adversely affect psoriasis through multiple mechanisms, such as increased susceptibility to infections, stimulation of lymphocyte and keratinocyte proliferation, and production of proinflammatory cytokines. Moreover, alcohol misuse can predispose to a greater risk of liver disease and potential drug interactions. Alcoholic and non-alcoholic liver diseases have both been found to be common in psoriatic patients. Tumor necrosis factor (TNF)-alpha, a key cytokine in psoriasis pathogenesis, has been found to have a crucial role in alcoholic hepatitis, and small preliminary studies have evaluated the effect of anti-TNF therapy in this condition. However, the use of anti-TNF-α drugs in alcoholic hepatitis is still controversial and needs to be further investigated. In this review, the relationship between alcohol and psoriasis will be reviewed and discussed, taking also into account recent findings related to liver disease and therapeutic implications.

  3. Functional Conservation and Divergence of Four Ginger AP1/AGL9 MADS–Box Genes Revealed by Analysis of Their Expression and Protein–Protein Interaction, and Ectopic Expression of AhFUL Gene in Arabidopsis

    PubMed Central

    Song, Juanjuan; Sun, Wei; Xia, Kuaifei; Liao, Jingping; Zhang, Mingyong

    2014-01-01

    Alpinia genus are known generally as ginger–lilies for showy flowers in the ginger family, Zingiberaceae, and their floral morphology diverges from typical monocotyledon flowers. However, little is known about the functions of ginger MADS–box genes in floral identity. In this study, four AP1/AGL9 MADS–box genes were cloned from Alpinia hainanensis, and protein–protein interactions (PPIs) and roles of the four genes in floral homeotic conversion and in floral evolution are surveyed for the first time. AhFUL is clustered to the AP1lineage, AhSEP4 and AhSEP3b to the SEP lineage, and AhAGL6–like to the AGL6 lineage. The four genes showed conserved and divergent expression patterns, and their encoded proteins were localized in the nucleus. Seven combinations of PPI (AhFUL–AhSEP4, AhFUL–AhAGL6–like, AhFUL–AhSEP3b, AhSEP4–AhAGL6–like, AhSEP4–AhSEP3b, AhAGL6–like–AhSEP3b, and AhSEP3b–AhSEP3b) were detected, and the PPI patterns in the AP1/AGL9 lineage revealed that five of the 10 possible combinations are conserved and three are variable, while conclusions cannot yet be made regarding the other two. Ectopic expression of AhFUL in Arabidopsis thaliana led to early flowering and floral organ homeotic conversion to sepal–like or leaf–like. Therefore, we conclude that the four A. hainanensis AP1/AGL9 genes show functional conservation and divergence in the floral identity from other MADS–box genes. PMID:25461565

  4. Alcohol conversion

    DOEpatents

    Wachs, Israel E.; Cai, Yeping

    2002-01-01

    Preparing an aldehyde from an alcohol by contacting the alcohol in the presence of oxygen with a catalyst prepared by contacting an intimate mixture containing metal oxide support particles and particles of a catalytically active metal oxide from Groups VA, VIA, or VIIA, with a gaseous stream containing an alcohol to cause metal oxide from the discrete catalytically active metal oxide particles to migrate to the metal oxide support particles and to form a monolayer of catalytically active metal oxide on said metal oxide support particles.

  5. Molecular mechanisms of hepatic apoptosis

    PubMed Central

    Wang, K

    2014-01-01

    Apoptosis is a prominent feature of liver diseases. Causative factors such as alcohol, viruses, toxic bile acids, fatty acids, drugs, and immune response, can induce apoptotic cell death via membrane receptors and intracellular stress. Apoptotic signaling network, including membrane death receptor-mediated cascade, reactive oxygen species (ROS) generation, endoplasmic reticulum (ER) stress, lysosomal permeabilization, and mitochondrial dysfunction, is intermixed each other, but one mechanism may dominate at a particular stage. Mechanisms of hepatic apoptosis are complicated by multiple signaling pathways. The progression of liver disease is affected by the balance between apoptotic and antiapoptotic capabilities. Therapeutic options of liver injury are impacted by the clear understanding toward mechanisms of hepatic apoptosis. PMID:24434519

  6. Alcoholic ketoacidosis

    MedlinePlus

    Tests may include: Arterial blood gases (measure the acid/base balance and oxygen level in blood) Blood alcohol ... PA: Elsevier Saunders; 2013:chap 161. Seifter JL. Acid-Base disorders. In: Goldman L, Schafer AI, eds. Goldman's ...

  7. Alcohol withdrawal

    MedlinePlus

    ... Seeing or feeling things that aren't there (hallucinations) Seizures Severe confusion ... alcohol withdrawal. You will be watched closely for hallucinations and other signs of delirium tremens. Treatment may ...

  8. Hepatitis B virus (image)

    MedlinePlus

    Hepatitis B is also known as serum hepatitis and is spread through blood and sexual contact. It is ... population. This photograph is an electronmicroscopic image of hepatitis B virus particles. (Image courtesy of the Centers for ...

  9. What Is Hepatitis?

    MedlinePlus

    ... Twitter Facebook Google + iTunes Play Store What is hepatitis? Online Q&A Reviewed July 2016 Q: What ... Question and answer archives Submit a question World Hepatitis Day Know hepatitis - Act now Event notice Key ...

  10. Drug-induced hepatitis

    MedlinePlus

    Toxic hepatitis ... to get liver damage. Some drugs can cause hepatitis with small doses, even if the liver breakdown ... liver. Many different drugs can cause drug-induced hepatitis. Painkillers and fever reducers that contain acetaminophen are ...

  11. [Clinical and biological specificities of female alcoholism].

    PubMed

    Limosin, F

    2002-01-01

    Even though the number of alcohol-dependent women is only about 1/3 of the number of alcoholic men, the alcoholism in women, by its clinical features and its course, is the source of therapeutic and economic stakes, particularly in young women among whom an increase of alcohol consumption related problems is reported. Another specificity of the female alcoholism is the lack of care seeking, whereas women have tendency globally to solicit more often care structures than men. Women represent only 1/4 of the overall treated alcoholic patients. The main explanation for this phenomenon is the pejorative social and moral connotation of the female alcoholism, with frequent feelings of shame and deep guilt, that also account for the frequency of hidden and lonely alcohol intakes. The female alcoholism is essentially characterized by an increased vulnerability to the toxic effects of the alcohol, whereas the pathological consumption starts later and with smaller daily amounts. Most studies have revealed a higher vulnerability in women to somatic complications directly attributable to the alcohol organs toxicity, such as hepatic cirrhosis and cardiovascular complications (high blood pressure, non obstructive cardiomyopathy). The reported brain morphological abnormalities could also occur more precociously in alcoholic women than in men. A decreased corpus callosum size among alcoholic women, but not in alcoholic men, was thus found in a recent study, compared with healthy controls. Among the different hypothesis proposed to explain this increased alcohol toxicity, the most incriminated is higher alcohol blood rates for the same ingested amount, mainly of the fact of a lower size with a weaker proportion of the bodily total water, but also of weaker concentrations of gastro-intestinal tract ADH, or of a longer metabolism during some menstrual phases. Indeed, some experimental studies on animal showed that the alcohol toxic effects may occur only from a threshold of alcohol

  12. Assessing Antigenic Drift of Seasonal Influenza A(H3N2) and A(H1N1)pdm09 Viruses.

    PubMed

    Tewawong, Nipaporn; Prachayangprecha, Slinporn; Vichiwattana, Preeyaporn; Korkong, Sumeth; Klinfueng, Sirapa; Vongpunsawad, Sompong; Thongmee, Thanunrat; Theamboonlers, Apiradee; Poovorawan, Yong

    2015-01-01

    Under selective pressure from the host immune system, antigenic epitopes of influenza virus hemagglutinin (HA) have continually evolved to escape antibody recognition, termed antigenic drift. We analyzed the genomes of influenza A(H3N2) and A(H1N1)pdm09 virus strains circulating in Thailand between 2010 and 2014 and assessed how well the yearly vaccine strains recommended for the southern hemisphere matched them. We amplified and sequenced the HA gene of 120 A(H3N2) and 81 A(H1N1)pdm09 influenza virus samples obtained from respiratory specimens and calculated the perfect-match vaccine efficacy using the pepitope model, which quantitated the antigenic drift in the dominant epitope of HA. Phylogenetic analysis of the A(H3N2) HA1 genes classified most strains into genetic clades 1, 3A, 3B, and 3C. The A(H3N2) strains from the 2013 and 2014 seasons showed very low to moderate vaccine efficacy and demonstrated antigenic drift from epitopes C and A to epitope B. Meanwhile, most A(H1N1)pdm09 strains from the 2012-2014 seasons belonged to genetic clades 6A, 6B, and 6C and displayed the dominant epitope mutations at epitopes B and E. Finally, the vaccine efficacy for A(H1N1)pdm09 (79.6-93.4%) was generally higher than that of A(H3N2). These findings further confirmed the accelerating antigenic drift of the circulating influenza A(H3N2) in recent years.

  13. Paracetamol, alcohol and the liver

    PubMed Central

    Prescott, Laurie F

    2000-01-01

    It is claimed that chronic alcoholics are at increased risk of paracetamol (acetaminophen) hepatotoxicity not only following overdosage but also with its therapeutic use. Increased susceptibility is supposed to be due to induction of liver microsomal enzymes by ethanol with increased formation of the toxic metabolite of paracetamol. However, the clinical evidence in support of these claims is anecdotal and the same liver damage after overdosage occurs in patients who are not chronic alcoholics. Many alcoholic patients reported to have liver damage after taking paracetamol with ‘therapeutic intent’ had clearly taken substantial overdoses. No proper clinical studies have been carried out to investigate the alleged paracetamol–alcohol interaction and acute liver damage has never been produced by therapeutic doses of paracetamol given as a challenge to a chronic alcoholic. The paracetamol–alcohol interaction is complex; acute and chronic ethanol have opposite effects. In animals, chronic ethanol causes induction of hepatic microsomal enzymes and increases paracetamol hepatotoxicity as expected (ethanol primarily induces CYP2E1 and this isoform is important in the oxidative metabolism of paracetamol). However, in man, chronic alcohol ingestion causes only modest (about twofold) and short-lived induction of CYP2E1, and there is no corresponding increase (as claimed) in the toxic metabolic activation of paracetamol. The paracetamol–ethanol interaction is not specific for any one isoform of cytochrome P450, and it seems that isoenzymes other than CYP2E1 are primarily responsible for the oxidative metabolism of paracetamol in man. Acute ethanol inhibits the microsomal oxidation of paracetamol both in animals and man. This protects against liver damage in animals and there is evidence that it also does so in man. The protective effect disappears when ethanol is eliminated and the relative timing of ethanol and paracetamol intake is critical. In many of the reports

  14. A 65 Ah rechargeable lithium molybdenum disulfide battery

    NASA Technical Reports Server (NTRS)

    Brandt, K.

    1986-01-01

    A rechargeable lithium molybdenum disulfide battery which has a number of superior performance characteristics which includes a high energy density, a high power density, and a long charge retention time was developed. The first cell sizes developed included a C size cell and an AA size cell. Over the last two years, a project to demonstrate the feasibility of the scale up to this technology to a BC size cell with 65 Ah capacity was undertaken. The objective was to develop, build, and test a .6 kWh storage battery consisting of 6 BC cells in series.

  15. Calorimetry of 25 Ah lithium/thionyl chloride cells

    NASA Technical Reports Server (NTRS)

    Johnson, C. J.; Dawson, S.

    1991-01-01

    Heat flow measurements of 25-Ah lithium thionyl chloride cells provided a method to calculate an effective thermal potential, E(TP) of 3.907 V. The calculation is useful to determine specific heat generation of this cell chemistry and design. The E(TP) value includes heat generation by electrochemical cell reactions, competitive chemical reactions, and resistance heating at the tabs, connectors, and leads. Heat flow was measured while applying electrical loads to the cell in an isothermal calorimeter set at 0, 20, and 60 C.

  16. Deciding to quit drinking alcohol

    MedlinePlus

    ... Alcohol abuse - quitting drinking; Quitting drinking; Quitting alcohol; Alcoholism - deciding to quit ... pubmed/23698791 . National Institute on Alcohol Abuse and Alcoholism. Alcohol and health. www.niaaa.nih.gov/alcohol- ...

  17. Hepatic ethanol elimination kinetics in patients with cirrhosis

    PubMed Central

    DAM, GITTE; SØRENSEN, MICHAEL; MUNK, OLE LAJORD; KEIDING, SUSANNE

    2011-01-01

    Objective To address the question of whether increased ethanol elimination in alcoholics can be ascribed to increased metabolism via alcohol dehydrogenase (ADH; Km around 0.2 mM) or the microsomal ethanol-oxidizing system (MEOS; Km 10 mM) by kinetic analysis of hepatic ethanol elimination in recently drinking patients with alcoholic cirrhosis and healthy subjects. A further objective was to investigate whether systemic clearance of ethanol at low arterial ethanol concentrations can be used as a measure of hepatic blood flow. Material and methods Six patients with alcoholic cirrhosis were enrolled after 2 days of abstinence, along with 6 healthy subjects. Ethanol was administered as 6 successive infusions in increasing doses. Arterial and hepatic venous blood concentrations of ethanol were measured; hepatic blood flow was measured simultaneously. Kinetic parameters were calculated according to the sinusoidal perfusion model of enzymatic elimination by the intact liver. Results Mean hepatic Km for ethanol was 0.16 mM (range 0.09–0.36) in healthy subjects and 0.36 mM (range 0.16–0.69) in patients with cirrhosis (p>0.3), both compatible with the Km for ADH. The two groups of subjects had similar Vmax values (p>0.3). Extrahepatic elimination of ethanol accounted for more than 50% of total elimination in both groups, which precludes the use of systemic clearance as a measure of hepatic blood flow. Conclusions The results support the hypothesis that ADH remains the main pathway for hepatic elimination of ethanol in recently drinking patients with alcoholic cirrhosis. We interpret this as evidence against a significant contribution of MEOS in vivo. PMID:19404864

  18. Relation among cytochrome P450, AH-active PCB congeners and dioxin equivalents in pipping black-crowned night-heron embryos

    USGS Publications Warehouse

    Rattner, B.A.; Hatfield, J.S.; Melancon, M.J.; Custer, T.W.; Tillitt, D.E.

    1994-01-01

    Pipping black-crowned night-heron (Nycticorax nycticorax) embryos were collected from a relatively uncontaminated site (next to Chincoteague National Wildlife Refuge, VA) and three polluted sites (Cat Island, Green Bay, Lake Michigan, WI; Bair Island, San Francisco Bay, CA; West Marin Island, San Francisco Bay, CA). Hepatic cytochrome P-450-associated monooxygenases and cytochrome P-450 proteins, induced up to 85-fold relative to the reference site, were associated with concentrations of total polychlorinated biphenyls (PCBs) and 11 PCB congeners that are presumed to express toxicity through the arylhydrocarbon (Ah) receptor. Multiple regression revealed that up to 86% of the variation of cytochrome P450 measurements was accounted for by variation in the concentration of these PCB congeners. Toxic equivalents (TEQs) of sample extracts, predicted mathematically (summed product of PCB congener concentrations and toxic equivalency factors), and dioxin equivalents (TCDD-EQs), derived by bioassay (ethoxyresorufin-O-dealkylase activity of treated H4IIE rat hepatoma cells), were greatest in Cat Island samples. Cytochrome P450-associated monooxygenases and cytochrome P450 proteins were related to TEQs and TCDD-EQs; adjusted r-2 often exceeded 0.5 for the relation among mathematically predicted TEQs and cytochrome P450 measurements. These data extend previous observations in heron embryos of an association between P450 and total PCB burdens to include Ah-active PCB congeners, and presumably other compounds, which interact similarly with the Ah receptor. Benzyloxyresorufin O-dealkylase, ethoxyresorufin O-dealkylase, and cytochrome P450 1A appear to be the most reliable measures of exposure to Ah-active PCB congeners in black-crowned night-heron embryos. These findings provide further evidence that cytochrome P450-associated parameters have considerable value as a biomarker for assessing environmental contamination of wetlands.

  19. Relation among cytochrome P450, Ah-active PCB congeners and dioxin equivalents in pipping black-crowned night-heron embryos

    SciTech Connect

    Rattner, B.A.; Hatfield, J.S.; Melancon, M.J.; Custer, T.W. . Patuxent Environmental Science Center); Tillitt, D.E. . Midwest Science Center)

    1994-11-01

    Pipping black-crowned night-heron (Nycticorax nycticorax) embryos were collected from a relatively uncontaminated site (next to Chincoteague National Wildlife Refuge, VA) and three polluted sites (Cat Island, Green Bay, Lake Michigan, WI; Bair Island, San Francisco Bay, CA; West Marin Island, San Francisco Bay, CA). Hepatic cytochrome P450-associated mono-oxygenates and cytochrome P450 proteins, induced up to 85-fold relative to the reference site, were associated with concentrations of total polychlorinated biphenyls (PCBs) and 11 PCB congeners that are presumed to express toxicity through the arylhydrocarbon (Ah) receptor. Multiple regression revealed that up to 86% of the variation of cytochrome P450 measurements was accounted for by variation in the concentration of these PCB congeners. Toxic equivalents (TEQs) of sample extracts, predicted mathematically (summed product of PCB congener concentrations and toxic equivalency factors), and dioxin equivalents (TCDD-EQs), derived by bioassay (ethoxyresorufin-O-dealkylase activity of treated H4IIE rat hepatoma cells), were greatest in Cat Island samples. Cytochrome P450-associated monooxygenases and cytochrome P450 proteins were related to TEQs and TCDD-EQs; adjusted r[sup 2] often exceeded 0.5 for the relation among mathematically predicted TEQs and cytochrome P450 measurements. These data extend previous observations in heron embryos of an association between P450 and total PCB burdens to include Ah-active PCB congeners, and presumably other compounds, which interact similarly with the AH receptor. Benzyloxyresorufin O-dealkylase, ethoxyresorufin O-dealkylase, and cytochrome P450 1A appear to be the most reliable measures of exposure to Ah-active PCB congeners in black-crowned night-heron embryos. These findings provide further evidence that cytochrome P450-associated parameters have considerable value as a biomarker for assessing environmental contamination of wetlands.

  20. Relation among cytochrome P450, Ah-active PCB congeners and dioxin equivalents in pipping black- crowned night-heron embryos

    USGS Publications Warehouse

    Rattner, B.A.; Hatfield, J.S.; Melancon, M.J.; Custer, T.W.; Tillitt, D.E.

    1994-01-01

    Pipping black-crowned night-heron (Nycticorax nycticorax) embryos were collected from a relatively uncontaminated site (next to Chincoteague National Wildlife Refuge, VA) and three polluted sites (Cat Island, Green Bay, Lake Michigan, WI; Bair Island, San Francisco Bay, CA; West Marin Island, San Francisco Bay, CA). Hepatic cytochrome P450-associated monooxygenases and cytochrome P450 proteins, induced up to 85- fold relative to the reference site, were associated with concentrations of total polychlorinated biphenyls (PCBs) and 11 PCB congeners that are presumed to express toxicity through the arylhydrocarbon (Ah) receptor. Multiple regression revealed that up to 86% of the variation of cytochrome P450 measurements was accounted for by variation in the concentration of these PCB congeners. Toxic equivalents (TEQs) of sample extracts, predicted mathematically (summed product of PCB congener concentrations and toxic equivalency factors), and dioxin equivalents (TCDD-EQs), derived by bioassay (ethoxyresorufin-O-dealkylase activity of treated H4IIE rat hepatoma cells), were greatest in Cat Island samples. Cytochrome P450-associated monooxygenases and cytochrome P450 proteins were related to TEQs and TCDD-EQs; adjusted r super(2) often exceeded 0.5 for the relation among mathematically predicted TEQs and cytochrome P450 measurements. These data extend previous observations in heron embryos of an association between P450 and total PCB burdens to include Ah- active PCB congeners, and presumably other compounds, which interact similarly with the Ah receptor. Benzyloxyresorufin O-dealkylase, ethoxyresorufin O-dealkylase, and cytochrome P450 1A appear to be the most reliable measures of exposure to Ah-active PCB congeners in black-crowned night-heron embryos. These findings provide further evidence that cytochrome P450-associated parameters have considerable value as a biomarker for assessing environmental contamination of wetlands.

  1. Linking Ah receptor mediated effects of sediments and impacts on fish to key pollutants in the Yangtze Three Gorges Reservoir, China - A comprehensive perspective.

    PubMed

    Floehr, Tilman; Scholz-Starke, Björn; Xiao, Hongxia; Hercht, Hendrik; Wu, Lingling; Hou, Junli; Schmidt-Posthaus, Heike; Segner, Helmut; Kammann, Ulrike; Yuan, Xingzhong; Roß-Nickoll, Martina; Schäffer, Andreas; Hollert, Henner

    2015-12-15

    The Three Gorges Reservoir (TGR), created in consequence of the Yangtze River's impoundment by the Three Gorges Dam, faces numerous anthropogenic impacts that challenge its unique ecosystem. Organic pollutants, particularly aryl hydrocarbon receptor (AhR) agonists, have been widely detected in the Yangtze River, but only little research was yet done on AhR-mediated activities. Hence, in order to assess effects of organic pollution, with particular focus on AhR-mediated activities, several sites in the TGR area were examined applying the "triad approach". It combines chemical analysis, in vitro, in vivo and in situ investigations to a holistic assessment. Sediments and the benthic fish species Pelteobagrus vachellii were sampled in 2011/2012, respectively, to identify relevant endpoints. Sediment was tested in vitro with the ethoxyresorufin-O-deethylase (EROD) induction assay, and in vivo with the Fish Embryo Toxicity Test and Sediment Contact Assay with Danio rerio. Activities of phase I (EROD) and phase II (glutathione-S-transferase) biotransformation enzymes, pollutant metabolites and histopathological alterations were studied in situ in P. vachellii. EROD induction was tested in vitro and in situ to evaluate possible relationships. Two sites, near Chongqing and Kaixian city, were identified as regional hot-spots and further investigated in 2013. The sediments induced in the in vitro/in vivo bioassays AhR-mediated activities and embryotoxic/teratogenic effects - particularly on the cardiovascular system. These endpoints could be significantly correlated to each other and respective chemical data. However, particle-bound pollutants showed only low bioavailability. The in situ investigations suggested a rather poor condition of P. vachellii, with histopathological alterations in liver and excretory kidney. Fish from Chongqing city exhibited significant hepatic EROD induction and obvious parasitic infestations. The polycyclic aromatic hydrocarbon (PAH) metabolite 1

  2. Linking Ah receptor mediated effects of sediments and impacts on fish to key pollutants in the Yangtze Three Gorges Reservoir, China - A comprehensive perspective.

    PubMed

    Floehr, Tilman; Scholz-Starke, Björn; Xiao, Hongxia; Hercht, Hendrik; Wu, Lingling; Hou, Junli; Schmidt-Posthaus, Heike; Segner, Helmut; Kammann, Ulrike; Yuan, Xingzhong; Roß-Nickoll, Martina; Schäffer, Andreas; Hollert, Henner

    2015-12-15

    The Three Gorges Reservoir (TGR), created in consequence of the Yangtze River's impoundment by the Three Gorges Dam, faces numerous anthropogenic impacts that challenge its unique ecosystem. Organic pollutants, particularly aryl hydrocarbon receptor (AhR) agonists, have been widely detected in the Yangtze River, but only little research was yet done on AhR-mediated activities. Hence, in order to assess effects of organic pollution, with particular focus on AhR-mediated activities, several sites in the TGR area were examined applying the "triad approach". It combines chemical analysis, in vitro, in vivo and in situ investigations to a holistic assessment. Sediments and the benthic fish species Pelteobagrus vachellii were sampled in 2011/2012, respectively, to identify relevant endpoints. Sediment was tested in vitro with the ethoxyresorufin-O-deethylase (EROD) induction assay, and in vivo with the Fish Embryo Toxicity Test and Sediment Contact Assay with Danio rerio. Activities of phase I (EROD) and phase II (glutathione-S-transferase) biotransformation enzymes, pollutant metabolites and histopathological alterations were studied in situ in P. vachellii. EROD induction was tested in vitro and in situ to evaluate possible relationships. Two sites, near Chongqing and Kaixian city, were identified as regional hot-spots and further investigated in 2013. The sediments induced in the in vitro/in vivo bioassays AhR-mediated activities and embryotoxic/teratogenic effects - particularly on the cardiovascular system. These endpoints could be significantly correlated to each other and respective chemical data. However, particle-bound pollutants showed only low bioavailability. The in situ investigations suggested a rather poor condition of P. vachellii, with histopathological alterations in liver and excretory kidney. Fish from Chongqing city exhibited significant hepatic EROD induction and obvious parasitic infestations. The polycyclic aromatic hydrocarbon (PAH) metabolite 1

  3. Identification of TMPRSS2 as a Susceptibility Gene for Severe 2009 Pandemic A(H1N1) Influenza and A(H7N9) Influenza.

    PubMed

    Cheng, Zhongshan; Zhou, Jie; To, Kelvin Kai-Wang; Chu, Hin; Li, Cun; Wang, Dong; Yang, Dong; Zheng, Shufa; Hao, Ke; Bossé, Yohan; Obeidat, Ma'en; Brandsma, Corry-Anke; Song, You-Qiang; Chen, Yu; Zheng, Bo-Jian; Li, Lanjuan; Yuen, Kwok-Yung

    2015-10-15

    The genetic predisposition to severe A(H1N1)2009 (A[H1N1]pdm09) influenza was evaluated in 409 patients, including 162 cases with severe infection and 247 controls with mild infection. We prioritized candidate variants based on the result of a pilot genome-wide association study and a lung expression quantitative trait locus data set. The GG genotype of rs2070788, a higher-expression variant of TMPRSS2, was a risk variant (odds ratio, 2.11; 95% confidence interval, 1.18-3.77; P = .01) to severe A(H1N1)pdm09 influenza. A potentially functional single-nucleotide polymorphism, rs383510, accommodated in a putative regulatory region was identified to tag rs2070788. Luciferase assay results showed the putative regulatory region was a functional element, in which rs383510 regulated TMPRSS2 expression in a genotype-specific manner. Notably, rs2070788 and rs383510 were significantly associated with the susceptibility to A(H7N9) influenza in 102 patients with A(H7N9) influenza and 106 healthy controls. Therefore, we demonstrate that genetic variants with higher TMPRSS2 expression confer higher risk to severe A(H1N1)pdm09 influenza. The same variants also increase susceptibility to human A(H7N9) influenza.

  4. Alcohol effects on drug-nutrient interactions.

    PubMed

    Seitz, H K

    1985-01-01

    The interaction of ethanol with drugs and xenobiotics is complex because ethanol can affect any of the following steps; absorption, plasma protein binding, hepatic blood flow, distribution, hepatic uptake of drugs, and phase I and II hepatic metabolism. The ingestion of ethanol can lead to malabsorption of a variety of nutrients and can modify the absorption of various drugs. High concentrations of ethanol in conjunction with aspirin causes gastric mucosal damage. The principal effect of acute ethanol ingestion on drug metabolism is inhibition of microsomal drug metabolism. The synergistic effects of ethanol on central nervous system depressants can be explained by this mechanism. In contrast, chronic ethanol consumption increases mixed function oxidation and drug metabolism. The cross tolerance between ethanol and sedatives in chronic alcoholics may be due to this effect of alcohol. In addition, enhanced production of hepatotoxic products from certain drugs and xenobiotics and an increased activation of procarcinogens to carcinogens can result from this microsomal induction. The increased susceptibility to hepatotoxins and the enhanced carcinogenesis in the alcoholic may be explained by this fact. Other effects of the interaction between drugs and ethanol are the result of changes in organ susceptibility, best demonstrated for the central nervous system. Subsequently, the presence of liver disease has a great effect on drug metabolism in alcoholics.

  5. AH-64 IHADSS aviator vision experiences in Operation Iraqi Freedom

    NASA Astrophysics Data System (ADS)

    Hiatt, Keith L.; Rash, Clarence E.; Harris, Eric S.; McGilberry, William H.

    2004-09-01

    Forty AH-64 Apache aviators representing a total of 8564 flight hours and 2260 combat hours during Operation Iraqi Freedom and its aftermath were surveyed for their visual experiences with the AH-64's monocular Integrated Helmet and Display Sighting System (IHADSS) helmet-mounted display in a combat environment. A major objective of this study was to determine if the frequencies of reports of visual complaints and illusions reported in the previous studies, addressing mostly benign training environments, differ in the more stressful combat environments. The most frequently reported visual complaints, both while and after flying, were visual discomfort and headache, which is consistent with previous studies. Frequencies of complaints after flying in the current study were numerically lower for all complaint types, but differences from previous studies are statistically significant only for visual discomfort and disorientation (vertigo). With the exception of "brownout/whiteout," reports of degraded visual cues in the current study were numerically lower for all types, but statistically significant only for impaired depth perception, decreased field of view, and inadvertent instrumental meteorological conditions. This study also found statistically lower reports of all static and dynamic illusions (with one exception, disorientation). This important finding is attributed to the generally flat and featureless geography present in a large portion of the Iraqi theater and to the shift in the way that the aviators use the two disparate visual inputs presented by the IHADSS monocular design (i.e., greater use of both eyes as opposed to concentrating primarily on display imagery).

  6. Aeroelastic characteristics of the AH-64 bearingless tail rotor

    NASA Technical Reports Server (NTRS)

    Banerjee, D.

    1988-01-01

    The results of a wind tunnel test program to determine the performance loads and dynamic characteristics of the Composite Flexbeam Tail Rotor (CFTR) for the AH-64 Advanced Attack Helicopter are reported. The CFTR uses an elastomeric shear attachment of the flexbeam to the hub to provide soft-inplane S-mode and stiff-inplane C-mode configuration. The properties of the elastomer were selected for proper frequency placement and scale damping of the inplane S-mode. Kinematic pitch-lag coupling was introduced to provide the first cyclic inplane C-mode damping at high collective pitch. The CFTR was tested in a wind tunnel over the full slideslip envelop of the AH-64. It is found that the rotor was aeroelastically stable throughout the complete collective pitch range and up to rotor speeds of 1403 rpm. The dynamic characteristics of the rotor were found to be satisfactory at all pitch angles and rotor speeds of the tunnel tests. The design characteristics of the rotor which permit the high performance characteristics are discussed. Several schematic drawings and photographs of the rotor are provided.

  7. Detecting Spread of Avian Influenza A(H7N9) Virus Beyond China.

    PubMed

    Millman, Alexander J; Havers, Fiona; Iuliano, A Danielle; Davis, C Todd; Sar, Borann; Sovann, Ly; Chin, Savuth; Corwin, Andrew L; Vongphrachanh, Phengta; Douangngeun, Bounlom; Lindblade, Kim A; Chittaganpitch, Malinee; Kaewthong, Viriya; Kile, James C; Nguyen, Hien T; Pham, Dong V; Donis, Ruben O; Widdowson, Marc-Alain

    2015-05-01

    During February 2013-March 2015, a total of 602 human cases of low pathogenic avian influenza A(H7N9) were reported; no autochthonous cases were reported outside mainland China. In contrast, since highly pathogenic avian influenza A(H5N1) reemerged during 2003 in China, 784 human cases in 16 countries and poultry outbreaks in 53 countries have been reported. Whether the absence of reported A(H7N9) outside mainland China represents lack of spread or lack of detection remains unclear. We compared epidemiologic and virologic features of A(H5N1) and A(H7N9) and used human and animal influenza surveillance data collected during April 2013-May 2014 from 4 Southeast Asia countries to assess the likelihood that A(H7N9) would have gone undetected during 2014. Surveillance in Vietnam and Cambodia detected human A(H5N1) cases; no A(H7N9) cases were detected in humans or poultry in Southeast Asia. Although we cannot rule out the possible spread of A(H7N9), substantial spread causing severe disease in humans is unlikely.

  8. Detecting Spread of Avian Influenza A(H7N9) Virus Beyond China

    PubMed Central

    Havers, Fiona; Iuliano, A. Danielle; Davis, C. Todd; Sar, Borann; Sovann, Ly; Chin, Savuth; Corwin, Andrew L.; Vongphrachanh, Phengta; Douangngeun, Bounlom; Lindblade, Kim A.; Chittaganpitch, Malinee; Kaewthong, Viriya; Kile, James C.; Nguyen, Hien T.; Pham, Dong V.; Donis, Ruben O.; Widdowson, Marc-Alain

    2015-01-01

    During February 2013–March 2015, a total of 602 human cases of low pathogenic avian influenza A(H7N9) were reported; no autochthonous cases were reported outside mainland China. In contrast, since highly pathogenic avian influenza A(H5N1) reemerged during 2003 in China, 784 human cases in 16 countries and poultry outbreaks in 53 countries have been reported. Whether the absence of reported A(H7N9) outside mainland China represents lack of spread or lack of detection remains unclear. We compared epidemiologic and virologic features of A(H5N1) and A(H7N9) and used human and animal influenza surveillance data collected during April 2013–May 2014 from 4 Southeast Asia countries to assess the likelihood that A(H7N9) would have gone undetected during 2014. Surveillance in Vietnam and Cambodia detected human A(H5N1) cases; no A(H7N9) cases were detected in humans or poultry in Southeast Asia. Although we cannot rule out the possible spread of A(H7N9), substantial spread causing severe disease in humans is unlikely. PMID:25897654

  9. Deciphering Dimerization Modes of PAS Domains: Computational and Experimental Analyses of the AhR:ARNT Complex Reveal New Insights Into the Mechanisms of AhR Transformation

    PubMed Central

    Corrada, Dario; Soshilov, Anatoly A.; Denison, Michael S.

    2016-01-01

    The Aryl hydrocarbon Receptor (AhR) is a transcription factor that mediates the biochemical response to xenobiotics and the toxic effects of a number of environmental contaminants, including dioxins. Recently, endogenous regulatory roles for the AhR in normal physiology and development have also been reported, thus extending the interest in understanding its molecular mechanisms of activation. Since dimerization with the AhR Nuclear Translocator (ARNT) protein, occurring through the Helix-Loop-Helix (HLH) and PER-ARNT-SIM (PAS) domains, is needed to convert the AhR into its transcriptionally active form, deciphering the AhR:ARNT dimerization mode would provide insights into the mechanisms of AhR transformation. Here we present homology models of the murine AhR:ARNT PAS domain dimer developed using recently available X-ray structures of other bHLH-PAS protein dimers. Due to the different reciprocal orientation and interaction surfaces in the different template dimers, two alternative models were developed for both the PAS-A and PAS-B dimers and they were characterized by combining a number of computational evaluations. Both well-established hot spot prediction methods and new approaches to analyze individual residue and residue-pairwise contributions to the MM-GBSA binding free energies were adopted to predict residues critical for dimer stabilization. On this basis, a mutagenesis strategy for both the murine AhR and ARNT proteins was designed and ligand-dependent DNA binding ability of the AhR:ARNT heterodimer mutants was evaluated. While functional analysis disfavored the HIF2α:ARNT heterodimer-based PAS-B model, most mutants derived from the CLOCK:BMAL1-based AhR:ARNT dimer models of both the PAS-A and the PAS-B dramatically decreased the levels of DNA binding, suggesting this latter model as the most suitable for describing AhR:ARNT dimerization. These novel results open new research directions focused at elucidating basic molecular mechanisms underlying the

  10. [Hepatic encephalopathy].

    PubMed

    Festi, Davide; Marasco, Giovanni; Ravaioli, Federico; Colecchia, Antonio

    2016-07-01

    Hepatic encephalopathy (HE) is a common complication of liver cirrhosis and it can manifest with a broad spectrum of neuropsychiatric abnormalities of varying severity, acuity and time course with important clinical implications. According to recent guidelines, HE has been classified into different types, depending on the severity of hepatic dysfunction, the presence of porto-systemic shunts and the number of previous episodes or persistent manifestations. From a clinical point of view, HE can be recognized as unimpaired, covert (that deals with minimal and grade 1 according to the grading of mental state), and overt (that is categorized from grade 2 to grade 4). Different and only partially known pathogenic mechanisms have been identified, comprising ammonia, inflammatory cytokines, benzodiazepine-like compounds and manganese deposition. Different therapeutic strategies are available for treating HE, in particular the overt HE, since covert HE needs to be managed case by case. Recognition and treatment of precipitating factors represent fundamental part of the management. The more effective treatments, which can be performed separately or combined, are represented by non-absorbable disaccharides (lactulose and lactitol) and the topic antibiotic rifaximin; other possible therapies, mainly used in patients non responders to previous treatments, are represented by branched chain amino acids and metabolic ammonia scavengers. PMID:27571468

  11. Protect Yourself from Hepatitis

    MedlinePlus

    ... develop yellowish eyes and skin. All the hepatitis viruses can cause acute, or short-term, hepatitis. Some can also cause chronic hepatitis, in which the infection lasts a long time, sometimes for your whole life. Chronic hepatitis can eventually lead to scarring of ...

  12. Alcohol-Dependent Liver Cell Necrosis in vitro: A New Model

    NASA Astrophysics Data System (ADS)

    Schanne, Francis A. X.; Zucker, Amy H.; Farber, John L.; Rubin, Emanuel

    1981-04-01

    In alcoholic liver injury, necrosis is involved in the progression from benign fatty liver to alcoholic hepatitis and cirrhosis. However, there is no practical model of alcohol-dependent liver cell necrosis. The calcium-dependent killing of cultured rat hepatocytes by two different membrane-active hepatotoxins, galactosamine and phalloidin, is potentiated by ethyl alcohol. This indicates that some general physical effect of alcohol on cellular membranes renders cells susceptible to otherwise nonlethal injuries. The in vitro model described in this report may thus be used to search for a general mechanism underlying alcohol-related tissue injury.

  13. [Hepatic amyloidosis as a rare differential diagnosis of progressive liver failure].

    PubMed

    Bettinger, Dominik; Lutz, Lisa; Schultheiß, Michael; Werner, Martin; Thimme, Robert; Neumann-Haefelin, Christoph

    2016-09-01

    Primary systemic amyloidosis is a rare disorder resulting in extracellular deposition of insoluble fibrils in different organs. Liver involvement has been reported. Since hepatic amyloidosis often presents clinically asymptomatic without specific laboratory or imaging hallmarks, diagnosis is challenging. However, cases of progressive hepatic failure due to liver amyloidosis have been reported. A 63 year old man presented with newly diagnosed ascites to our department. The patient reported occasional alcohol consumption. Viral hepatitis, genetic-metabolic causes as well as hepatic vascular disorders were excluded and ultrasound did not show any signs of liver cirrhosis or intraabdominal malignancy. Initially, alcoholic hepatitis was suspected. Due to the rapid deterioration of liver function, however, transjugular liver biopsy was performed showing light chain amyloidosis of kappa isotype. As diagnosis of hepatic amyloidosis is challenging, early liver biopsy is mandatory in patients with unexplained acute or chronic liver disease to exclude rare diseases with high mortality. PMID:27642740

  14. [Hepatic amyloidosis as a rare differential diagnosis of progressive liver failure].

    PubMed

    Bettinger, Dominik; Lutz, Lisa; Schultheiß, Michael; Werner, Martin; Thimme, Robert; Neumann-Haefelin, Christoph

    2016-09-01

    Primary systemic amyloidosis is a rare disorder resulting in extracellular deposition of insoluble fibrils in different organs. Liver involvement has been reported. Since hepatic amyloidosis often presents clinically asymptomatic without specific laboratory or imaging hallmarks, diagnosis is challenging. However, cases of progressive hepatic failure due to liver amyloidosis have been reported. A 63 year old man presented with newly diagnosed ascites to our department. The patient reported occasional alcohol consumption. Viral hepatitis, genetic-metabolic causes as well as hepatic vascular disorders were excluded and ultrasound did not show any signs of liver cirrhosis or intraabdominal malignancy. Initially, alcoholic hepatitis was suspected. Due to the rapid deterioration of liver function, however, transjugular liver biopsy was performed showing light chain amyloidosis of kappa isotype. As diagnosis of hepatic amyloidosis is challenging, early liver biopsy is mandatory in patients with unexplained acute or chronic liver disease to exclude rare diseases with high mortality.

  15. Fetal alcohol syndrome

    MedlinePlus

    Alcohol in pregnancy; Alcohol-related birth defects; Fetal alcohol effects; FAS ... varies. Almost none of these babies have normal brain development. Infants and children with fetal alcohol syndrome have many different problems, which can be ...

  16. Fetal Alcohol Spectrum Disorders

    MedlinePlus

    ... alcohol can cause a group of conditions called fetal alcohol spectrum disorders (FASDs). Effects can include physical and behavioral problems such ... alcohol syndrome is the most serious type of FASD. People with fetal alcohol syndrome have facial abnormalities, ...

  17. Alcoholic Liver Disease and Malnutrition

    PubMed Central

    McClain, Craig J.; Barve, Shirish S.; Barve, Ashutosh; Marsano, Luis

    2013-01-01

    Malnutrition, both protein energy malnutrition (PEM) and deficiencies in individual nutrients, is a frequent complication of alcoholic liver disease (ALD). Severity of malnutrition correlates with severity of ALD. Malnutrition also occurs in patients with cirrhosis due to etiologies other than alcohol. The mechanisms for malnutrition are multifactorial, and malnutrition frequently worsens in the hospital due to fasting for procedures and metabolic complications of liver disease, such as hepatic encephalopathy. Aggressive nutritional support is indicated in inpatients with ALD, and patients often need to be fed through an enteral feeding tube to achieve protein and calorie goals. Enteral nutritional support clearly improves nutrition status and may improve clinical outcome. Moreover, late-night snacks in outpatient cirrhotics improve nutritional status and lean body mass. Thus, with no FDA-approved therapy for ALD, careful nutritional intervention should be considered as frontline therapy. PMID:21284673

  18. Hepatic glucose and lipid metabolism.

    PubMed

    Jones, John G

    2016-06-01

    The liver has a central role in the regulation of systemic glucose and lipid fluxes during feeding and fasting and also relies on these substrates for its own energy needs. These parallel requirements are met by coordinated control of carbohydrate and lipid fluxes into and out of the Krebs cycle, which is highly tuned to nutrient availability and heavily regulated by insulin and glucagon. During progression of type 2 diabetes, hepatic carbohydrate and lipid biosynthesis fluxes become elevated, thus contributing to hyperglycaemia and hypertriacylglycerolaemia. Over this interval there are also significant fluctuations in hepatic energy state. To date, it is not known to what extent abnormal glucose and lipid fluxes are causally linked to altered energy states. Recent evidence that the glucose-lowering effects of metformin appear to be mediated by attenuation of hepatic energy generation places an additional spotlight on the interdependence of hepatic biosynthetic and oxidative fluxes. The transition from fasting to feeding results in a significant re-direction of hepatic glucose and lipid fluxes and may also incur a temporary hepatic energy deficit. At present, it is not known to what extent these variables are additionally modified by type 2 diabetes and/or non-alcoholic fatty liver disease. Thus, there is a compelling need to measure fluxes through oxidative, gluconeogenic and lipogenic pathways and determine their relationship with hepatic energy state in both fasting and fed conditions. New magnetic resonance-based technologies allow these variables to be non-invasively studied in animal models and humans. This review summarises a presentation given at the symposium entitled 'The liver in focus' at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Kenneth Cusi, DOI: 10.1007/s00125-016-3952-1 , and by Hannele Yki-Järvinen, DOI: 10.1007/s00125-016-3944-1 ) and a commentary by the Session Chair, Michael

  19. [Non-alcoholic fatty liver].

    PubMed

    Tagle Arrospide, Martín

    2003-01-01

    Non alcoholic fatty liver disease (NAFLD) and its more agressive form, non alcoholic steatohepatitis (NASH) are entities that are becoming subject of interest of the medical community in general, especially because of the increased prevalence of diabetes and obesity in the world population. There is solid evidence linking NAFLD with the so called metabolic syndrome or syndrome X, to the point of accepting hepatic steatosis and its spectrum as one more element of the latter, along with diabetes, hipertension, hypertriglyceridemia and obesity. Insulin resistance seems to be the common link between these entities. Clinical evaluation of every patient with abnormal aminotransferase levels should take into account non alcoholic fatty liver and its spectrum, especially if the subject is obese or diabetic. Despite the important developments in the field of imaging, currenty the only way to differentiate NASH from simple NAFLD is by performing a liver biopsy, which should be discussed extensively with the patient. The prognosis of simple NAFLD is generally benign, but if there is fibrosis, ballooning of the hepatocytes, inflammation and Mallory bodies there is risk to progression to cirrhosis. Liver histology in NAFLD is indistinguishable from alcoholic hepatitis, although the clinical course is generally more benign. Despite this long and protracted clinical course, an important number of subjects have complications of cirrhosis including hepatocellular carcinoma, and many patients require a liver transplantation. There is no specific treatment for this condition, although every therapeutic regimen should include a gradual and supervised weight reduction, a balanced diet and exercise, as well as correction of precipitant factors. There is currently no specific pharmacologic treatment for NASH or NAFLD. Current body of evidence and some pilot studies suggest that the future might be concentrated in agents improving insulin resistance. Meanwhile, we should do our best to

  20. Use of artificial sweeteners to promote alcohol consumption by rats.

    PubMed

    Plummer, J L; Hall, P M; Cmielewski, P L; Ilsley, A H; Ahern, M J

    1997-02-01

    Cirrhosis may be reliably produced in rats by exposing them intermittently to low levels of carbon tetrachloride vapour while feeding alcohol in the Lieber-DeCarli liquid diet. Providing the alcohol in drinking water that has been sweetened with sucrose is a cheaper and more convenient method but it does not yield reliable results. This study aimed to determine whether alcohol in drinking water sweetened with artificial sweeteners would give adequate alcohol intake to achieve the desired hepatic effects. Rats were fed alcohol (8% v/v) in drinking water sweetened with sucrose (5% w/v) (n = 12), or with one of the artificial sweeteners aspartame (0.025%), saccharin (0.025%) or cyclamate (0.05%) (n = 8 per agent). During the alcohol treatment the animals were exposed to carbon tetrachloride vapour, 40 ppm, six hours per night for five nights per week, over a period of 14 weeks. All groups achieved good alcohol intakes of 5-6 g/kg/day. Only one rat, in the aspartame group, became cirrhotic; all the others had varying degrees of fibrosis which did not differ significantly among the treatments. Although it was not effective in reliably achieving cirrhosis, sweetening the alcohol solution with artificial sweeteners led to reasonable alcohol intakes with resultant hepatic fibrosis, and without the high carbohydrate intake which occurs when sucrose is used.

  1. Allyl alcohol

    Integrated Risk Information System (IRIS)

    Allyl alcohol ; CASRN 107 - 18 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  2. Propargyl alcohol

    Integrated Risk Information System (IRIS)

    Propargyl alcohol ; CASRN 107 - 19 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic

  3. Isobutyl alcohol

    Integrated Risk Information System (IRIS)

    Isobutyl alcohol ; CASRN 78 - 83 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic E

  4. Alcohol project

    SciTech Connect

    Not Available

    1980-12-01

    The Great Western Sugar Company has announced plans for the construction of a $300 million plant for the production of fuel grade alcohol from corn. The plant at Reserve, Lousiana, will also produce high fructose corn syrup and animal feed by-products and will employ an additional 200 people.

  5. Hepatic Perfusion Therapy.

    PubMed

    Rajeev, Rahul; Gamblin, T Clark; Turaga, Kiran K

    2016-04-01

    Isolated hepatic perfusion uses the unique vascular supply of hepatic malignancies to deliver cytotoxic chemotherapy. The procedure involves vascular isolation of the liver and delivery of chemotherapy via the hepatic artery and extraction from retrohepatic vena cava. Benefits of hepatic perfusion have been observed in hepatic metastases of ocular melanoma and colorectal cancer and primary hepatocellular carcinoma. Percutaneous and prophylactic perfusions are avenues of ongoing research.

  6. Alcoholism and Minority Populations.

    ERIC Educational Resources Information Center

    Watts, Thomas D.; Wright, Roosevelt, Jr.

    1991-01-01

    Briefly discusses some aspects of the role of the state and the position of minorities in respect to alcoholism policies and services. Includes case study of a Black alcoholic. Refers readers to studies on Black alcoholism, Native American alcoholism, Hispanic alcoholism, and Asian-American alcoholism. (Author/NB)

  7. A case of acute hepatitis following mad honey ingestion.

    PubMed

    Sari Dogan, Fatma; Ozaydin, Vehbi; Incealtin, Onur; Guneysel, Ozlem; Demireller, Merve

    2015-12-01

    Acute hepatitis is characterized by liver inflammation and liver cell necrosis. The most frequently observed underlying cause thereof is viruses, but various other causes, such as alcohol, medication, or toxins may also lead thereto. In this paper, a case of acute hepatitis presenting with bradycardia, hypotension, and a prominent increase in liver enzymes following mad honey ingestion is discussed. Since there are only few cases of acute hepatitis following mad honey ingestion in the literature, we want to present this subject matter. PMID:27239626

  8. Emerging therapeutic targets for the treatment of hepatic fibrosis.

    PubMed

    Fagone, Paolo; Mangano, Katia; Pesce, Antonio; Portale, Teresa Rosanna; Puleo, Stefano; Nicoletti, Ferdinando

    2016-02-01

    Fibrosis represents a response to chronic injury, aimed at maintaining organ integrity. Hepatic fibrosis is mainly related to chronic viral hepatitis B or C (HBV or HCV), alcoholic and nonalcoholic steatohepatitis (NASH), and biliary diseases. A deep understanding of the cellular and molecular mechanisms underlying liver fibrosis has enabled the development of 'pathogenetic tailored' therapeutic interventions. However, effective drugs to prevent or revert hepatic fibrosis are still lacking. In this review, we discuss the cellular populations and the molecular pathways involved in liver fibrogenesis as well as the novel approaches currently being tested in clinical trials.

  9. Zafirlukast-induced acute hepatitis.

    PubMed

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

    2002-11-01

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

  10. Hepatology after Hepatitis C.

    PubMed

    Fitz, J Gregory

    2016-01-01

    The ∼90% probability of curing individual patients with hepatitis C virus (HCV)using direct-acting antivirals represents one of the most dramatic medical success stories of the modern era, and the journey from viral discovery to treatment occurred over just ∼25 years. The realities of the global burden of disease (2-3% of the world's population is infected), limited access to care and cost of treatment mean that HCV will continue to be a major problem for the next 25 years. But what if HCV (and hepatitis B) could be eradicated? Since liver transplantation and HCV management have been the mainstays of academic hepatology practice, where do we go from here? Unfortunately, we are in an era where the incidence and prevalence of liver diseases around the globe is increasing, and death from complications of cirrhosis is now among the top 10 causes in most countries; so hepatologists are expected to play a major role in the future. Despite remarkable progress, success at the population level is limited by the resource-intensive nature of caring for patients with end-stage disease. Accordingly, the major advances in the next decade are likely to focus on (i) the earlier identification of individuals and populations at higher risk for liver diseases, and (ii) initiation in high-risk populations of specific strategies for early detection and treatment of fibrosis, cancer and cirrhosis. The answers will lie in large part in the further exploration of the human genome in carefully phenotyped patients. Risk variants in the PNPLA3 gene represent the best example to date. The risk variants are common and are enriched in certain populations around the globe; and individuals that possess risk variants are more likely to have liver injury from fatty liver disease (even as children), alcohol and viral hepatitis. Further, those with liver injury are more likely to progress to cirrhosis and hepatoma. Similarly, in those with established liver disease, use of biomarkers and other

  11. Evaluation of Aroclor 1260 exposure in a mouse model of diet-induced obesity and non-alcoholic fatty liver disease

    SciTech Connect

    Wahlang, Banrida; Song, Ming; Beier, Juliane I.; Cameron Falkner, K.; Al-Eryani, Laila; Clair, Heather B.; Prough, Russell A.; Osborne, Tanasa S.; Malarkey, David E.; Christopher States, J.; Cave, Matthew C.

    2014-09-15

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with non-alcoholic fatty liver disease (NAFLD) in epidemiologic studies. The purpose of this study was to evaluate the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, in a mouse model of diet-induced obesity (DIO). Male C57Bl/6J mice were fed control diet or 42% high fat diet (HFD) and exposed to Aroclor 1260 (20 mg/kg or 200 mg/kg in corn oil) for 12 weeks. A glucose tolerance test was performed; plasma/tissues were obtained at necropsy for measurements of adipocytokine levels, histology, and gene expression. Aroclor 1260 exposure was associated with decreased body fat in HFD-fed mice but had no effect on blood glucose/lipid levels. Paradoxically, Aroclor 1260 + HFD co-exposed mice demonstrated increased hepatic inflammatory foci at both doses while the degree of steatosis did not change. Serum cytokines, ALT levels and hepatic expression of IL-6 and TNFα were increased only at 20 mg/kg, suggesting an inhibition of pro-inflammatory cytokine production at the 200 mg/kg exposure. Aroclor 1260 induced hepatic expression of cytochrome P450s including Cyp3a11 (Pregnane-Xenobiotic Receptor target) and Cyp2b10 (constitutive androstane receptor target) but Cyp2b10 inducibility was diminished with HFD-feeding. Cyp1a2 (aryl hydrocarbon Receptor target) was induced only at 200 mg/kg. In summary, Aroclor 1260 worsened hepatic and systemic inflammation in DIO. The results indicated a bimodal response of PCB-diet interactions in the context of inflammation which could potentially be explained by xenobiotic receptor activation. Thus, PCB exposure may be a relevant “second hit” in the transformation of steatosis to steatohepatitis. - Highlights: • Aroclor 1260 exposure decreased adiposity in mice fed with high fat diet • Aroclor 1260 exposure induced steatohepatitis in diet-induced obese mice • Aroclor 1260 (20 and 200 mg/kg) induced

  12. Non-Alcoholic Fatty Liver Disease in Children

    PubMed Central

    SINGER, CRISTINA; STANCU, POLIXENIA; COŞOVEANU, SIMONA; BOTU, ALINA

    2014-01-01

    In the last years, there has been extremely much information which reveals an alarming increase of obesity in children and, at the same time, an increase of the incidence of non-alcoholic fatty liver disease (NAFLD). NAFLD implies a wide range of affections starting from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH); the latter can evolve to cirrhosis and hepatic carcinoma. All these affections were noticed in children, too. The article presents data on the epidemiology, pathogeny, clinical and paraclinical findings, and treatment of NAFLD in children. PMID:25729601

  13. Attack helicopter (AH-1T) cockpit systems integration

    NASA Technical Reports Server (NTRS)

    Graf, V. A.

    1984-01-01

    This discussion summarizes the effort conducted by the BHTI Human Factors and Cockpit Arrangement group for a study and design of the integration of a cockpit control system for the AH 1T (TOW). The resulting design is a culmination of studies that were conducted using the existing configuration as a baseline and complementing it with new equipment and subsystems that fulfill the attack helicopter requirements for the foreseeable future. Of primary concern was the requirement to add a missile control system, with secondary considerations for improved NOE and night operations. In addition, growth capabilities for improved target acquisition, weapons delivery, and precise navigation was considered. Along with the addition of new equipment, the aircraft was assumed to have a central multiplex data bus system for information transfer throughout the aircraft and its subsystems.

  14. Human Infection with Highly Pathogenic A(H7N7) Avian Influenza Virus, Italy, 2013

    PubMed Central

    Rossini, Giada; Facchini, Marzia; Vaccari, Gabriele; Di Trani, Livia; Di Martino, Angela; Gaibani, Paolo; Vocale, Caterina; Cattoli, Giovanni; Bennett, Michael; McCauley, John W.; Rezza, Giovanni; Moro, Maria Luisa; Rangoni, Roberto; Finarelli, Alba Carola; Landini, Maria Paola; Castrucci, Maria Rita; Donatelli, Isabella

    2014-01-01

    During an influenza A(H7N7) virus outbreak among poultry in Italy during August–September 2013, infection with a highly pathogenic A(H7N7) avian influenza virus was diagnosed for 3 poultry workers with conjunctivitis. Genetic analyses revealed that the viruses from the humans were closely related to those from chickens on affected farms. PMID:25271444

  15. Pityriazepin and other potent AhR ligands isolated from Malassezia furfur yeast

    PubMed Central

    Mexia, Nikitia; Gaitanis, George; Velegraki, Aristea; Soshilov, Anatoly; Denison, Michael S.; Magiatis, Prokopios

    2015-01-01

    Malassezia furfur yeast strains isolated from diseased human skin preferentially biosynthesize indole alkaloids which can be detected in human skin and are highly potent activators of the aryl hydrocarbon receptor (AhR) and AhR-dependent gene expression. Chemical analysis of an EtOAc extract of a M. furfur strain obtained from diseased human skin and grown on L-tryptophan agar revealed several known AhR active tryptophan metabolites along with a previously unidentified compound, pityriazepin. While its structure resembled that of the known alkaloid pityriacitrin, the comprised pyridine ring had been transformed into an azepinone. The indoloazepinone scaffold of pityriazepin is extremely rare in nature and has only been reported once previously. Pityriazepin, like the other isolated compounds, was found to be a potent activator of the AhR-dependent reporter gene assays in recombinant cell lines derived from four different species, although significant species differences in relative potency was observed. The ability of pityriazepin to competitively bind to the AhR and directly stimulate AhR DNA binding classified it as a new naturally-occurring potent AhR agonist. Malassezia furfur produces an expanded collection of extremely potent naturally occurring AhR agonists, which produce their biological effects in a species-specific manner.1 PMID:25721496

  16. A historical perspective of influenza A(H1N2) virus.

    PubMed

    Komadina, Naomi; McVernon, Jodie; Hall, Robert; Leder, Karin

    2014-01-01

    The emergence and transition to pandemic status of the influenza A(H1N1)A(H1N1)pdm09) virus in 2009 illustrated the potential for previously circulating human viruses to re-emerge in humans and cause a pandemic after decades of circulating among animals. Within a short time of the initial emergence of A(H1N1)pdm09 virus, novel reassortants were isolated from swine. In late 2011, a variant (v) H3N2 subtype was isolated from humans, and by 2012, the number of persons infected began to increase with limited person-to-person transmission. During 2012 in the United States, an A(H1N2)v virus was transmitted to humans from swine. During the same year, Australia recorded its first H1N2 subtype infection among swine. The A(H3N2)v and A(H1N2)v viruses contained the matrix protein from the A(H1N1)pdm09 virus, raising the possibility of increased transmissibility among humans and underscoring the potential for influenza pandemics of novel swine-origin viruses. We report on the differing histories of A(H1N2) viruses among humans and animals.

  17. A Modified Delphi Study to Define "Ah Ha" Moments in Education Settings

    ERIC Educational Resources Information Center

    Pilcher, Jobeth

    2015-01-01

    Ah ha moments are often mentioned in education literature. These moments are suggested to be a powerful aspect of learning, yet limited research is present regarding this topic. Ah ha learning moments have also not been defined in the education literature, resulting in the likelihood that each educator and learner may have differing definitions.…

  18. Use of natural AhR ligands as potential therapeutic modalities against inflammatory disorders

    PubMed Central

    Busbee, Philip B; Rouse, Michael; Nagarkatti, Mitzi; Nagarkatti, Prakash S

    2014-01-01

    The aim of this review is to discuss research involving ligands for the aryl hydrocarbon receptor (AhR) and their role in immunomodulation. While activation of the AhR is well known for its ability to regulate the biochemical and toxic effects of environmental chemicals, more recently an exciting discovery has been made indicating that AhR ligation can also regulate T-cell differentiation, specifically through activation of Foxp3+ regulatory T cells (Tregs) and downregulation of the proinflammatory Th17 cells. Such findings have opened new avenues of research on the possibility of targeting the AhR to treat inflammatory and autoimmune diseases. Specifically, this review will discuss the current research involving natural and dietary AhR ligands. In addition, evidence indicating the potential use of these ligands in regulating inflammation in various diseases will be highlighted. The importance of the AhR in immunological processes can be illustrated by expression of this receptor on a majority of immune cell types. In addition, AhR signaling pathways have been reported to influence a number of genes responsible for mediating inflammation and other immune responses. As interest in the AhR and its ligands increases, it seems prudent to consolidate current research on the contributions of these ligands to immune regulation during the course of inflammatory diseases. PMID:23731446

  19. Antiviral activity of alcohol for surface disinfection.

    PubMed

    Moorer, W R

    2003-08-01

    Bacteria and viruses from the patient's mouth travel with dental splatter and spills. A surface disinfectant should possess antiviral activity as well as antibacterial action. Because of frequent and 'open' application in the dental office, such a disinfectant should be non-toxic, non-allergenic and safe for the hygienist. It now appears that high-concentration alcohol mixtures (i.e. 80% ethanol + 5% isopropanol) are not only excellent antibacterials, but quickly inactivate HIV as well as hepatitis B and hepatitis C viruses. Compared to alternative surface disinfectants, use of high-concentration alcohol for the spray-wipe-spray method of surface disinfection in dentistry appears safe and efficient. However, dried matter should be wiped and hydrated first.

  20. Viral hepatitis: Indian scenario.

    PubMed

    Satsangi, Sandeep; Chawla, Yogesh K

    2016-07-01

    Viral hepatitis is a cause for major health care burden in India and is now equated as a threat comparable to the "big three" communicable diseases - HIV/AIDS, malaria and tuberculosis. Hepatitis A virus and Hepatitis E virus are predominantly enterically transmitted pathogens and are responsible to cause both sporadic infections and epidemics of acute viral hepatitis. Hepatitis B virus and Hepatitis C virus are predominantly spread via parenteral route and are notorious to cause chronic hepatitis which can lead to grave complications including cirrhosis of liver and hepatocellular carcinoma. Around 400 million people all over the world suffer from chronic hepatitis and the Asia-Pacific region constitutes the epicentre of this epidemic. The present article would aim to cover the basic virologic aspects of these viruses and highlight the present scenario of viral hepatitis in India. PMID:27546957

  1. TCDD and omeprazole prime platelets through the aryl hydrocarbon receptor (AhR) non-genomic pathway.

    PubMed

    Pombo, Mónica; Lamé, Michael W; Walker, Naomi J; Huynh, Danh H; Tablin, Fern

    2015-05-19

    The role of the aryl hydrocarbon receptor (AhR) in hemostasis has recently gained increased attention. Here, we demonstrate, by qRT-PCR and western blot, that human platelets express both AhR mRNA and AhR protein. AhR protein levels increase in a dose dependent manner when incubated with either 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or omeprazole. Treatment of platelets with puromycin blocks increased AhR protein synthesis in the presence of AhR activators. Additionally, treatment of platelets with either activator results in phosphorylation of p38MAPK and cPLA2, two key signaling molecules in platelet activation pathways. Using the AhR competitive inhibitors alpha naphthoflavone and CH-223191, we show that phosphorylation of p38MAPK is AhR dependent. Further, inhibition of p38MAPK blocks downstream cPLA2 phosphorylation induced by TCDD or omeprazole. Treatment with AhR activators results in platelet priming, as demonstrated by increased platelet aggregation, which is inhibited by AhR antagonists. Our data support a model of the platelet AhR non-genomic pathway in which treatment with AhR activators results in increased expression of the AhR, phosphorylation of p38MAPK and cPLA2, leading to platelet priming in response to agonist. PMID:25797602

  2. Steatosis and hepatitis C

    PubMed Central

    Modaresi Esfeh, Jamak; Ansari-Gilani, Kianoush

    2016-01-01

    Hepatitis C virus (HCV) infection is a common liver disease worldwide with a high rate of chronicity (75–80%) in infected individuals. The chronic form of HCV leads to steatosis, cirrhosis and hepatocellualr carcinoma. Steatosis is prevalent in HCV patients (55%) due to a combination of viral factors (effect of viral proteins on some of the intracellular pathways) and host factors (overweight, insulin resistance, diabetes mellitus, and alcohol consumption). The response rates to treatment of chronic HCV with pegylated interferon (PEG-IFN) and (in the case of genotype-1 HCV, the most common infecting genotype in the USA) ribavirin (RBV) is low, with a sustained viral response rate ≤ 40%. Adding direct-acting antiviral agents—recently approved by the FDA—to the standard protocol has increased the response rate; however HCV-related end-stage liver disease is still the primary indication for liver transplantation in the USA. The focus of this article is on the interrelation between HCV, steatosis and metabolic syndrome. PMID:26276502

  3. Hepatitis C: liver transplantation.

    PubMed

    Metts, Julius; Carmichael, Lesley; Kokor, Winfred; Scharffenberg, Robert

    2014-12-01

    Hepatitis C virus (HCV)-related cirrhosis and hepatocellular carcinoma account for approximately 40% of the 6,000 adult liver transplantations performed each year in the United States. Survival rates are 76% to 83% at 2 years and 69% to 72% at 5 years. If eligible for surgery and in the absence of contraindications, any patient with HCV infection who develops decompensated liver disease or hepatocellular carcinoma is a candidate for liver transplantation. Most transplantation programs require that a patient with a history of alcohol or drug abuse be abstinent for at least 6 months and active in a substance abuse rehabilitation program. Prioritization for transplantation is based primarily on a patient's model for end-stage liver disease score, though other factors are considered. Complications after liver transplantation include recurrence of HCV infection, rejection of the transplanted liver, and an increased rate of infection because of immunosuppression. Various drugs are used to prevent infection and organ rejection. Liver transplant recipients also develop diabetes, hypertension, hyperlipidemia, renal dysfunction, osteopenia, and cancers at high rates, likely because of the effects of immunosuppressive drugs, particularly steroids and calcineurin inhibitors. The family physician's role in caring for liver transplant recipients often involves detection and management of these conditions. PMID:25478647

  4. Interstellar Alcohols

    NASA Technical Reports Server (NTRS)

    Charnley, S. B.; Kress, M. E.; Tielens, A. G. G. M.; Millar, T. J.

    1995-01-01

    We have investigated the gas-phase chemistry in dense cores where ice mantles containing ethanol and other alcohols have been evaporated. Model calculations show that methanol, ethanol, propanol, and butanol drive a chemistry leading to the formation of several large ethers and esters. Of these molecules, methyl ethyl ether (CH3OC2H5) and diethyl ether (C2H5)2O attain the highest abundances and should be present in detectable quantities within cores rich in ethanol and methanol. Gas-phase reactions act to destroy evaporated ethanol and a low observed abundance of gas-phase C,H,OH does not rule out a high solid-phase abundance. Grain surface formation mechanisms and other possible gas-phase reactions driven by alcohols are discussed, as are observing strategies for the detection of these large interstellar molecules.

  5. Hepatitis Information for the Public

    MedlinePlus

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

  6. Diabetes and Hepatitis B Vaccination

    MedlinePlus

    Diabetes and Hepatitis B Vaccination Information for Diabetes Educators What is hepatitis B? Hepatitis B is a contagious liver disease that results from infection with the hepatitis B virus. When first infected, a person can develop ...

  7. Alcohol use and safe drinking

    MedlinePlus

    ... RISKS OF ALCOHOL Alcohol increases the risk of: Alcoholism Falls, drownings, and other accidents Head, neck, stomach, ... pubmed/23698791 . National Institute on Alcohol Abuse and Alcoholism. Alcohol and your health. www.niaaa.nih.gov/ ...

  8. Alcohol and the heart: to abstain or not to abstain?

    PubMed

    Movva, Rajesh; Figueredo, Vincent M

    2013-04-15

    Alcohol has been consumed by most societies over the last 7000 years. Abraham Lincoln said "It has long been recognized that the problems with alcohol relate not to the use of a bad thing, but to the abuse of a good thing." Light to moderate alcohol consumption reduces the incidence of coronary heart disease (CHD), ischemic stroke, peripheral arterial disease, CHD mortality, and all-cause mortality, especially in the western populations. However, heavy alcohol consumption is detrimental causing cardiomyopathy, cardiac arrhythmias, hepatic cirrhosis, pancreatitis, and hemorrhagic stroke. In this article, we review the effects of alcohol on CHD, individual cardiovascular risk factors, cardiomyopathy, and cardiac arrhythmias, including the most recent evidence of the effects of alcohol on CHD.

  9. Precursor systems analyses of automated highway systems. Activity area K AHS roadway operational analysis. Final report, September 1993-November 1994

    SciTech Connect

    Schulze, R.; Roper, D.; Tsao, J.; Michael, B.

    1995-05-01

    This study considers the roadway operational requirements of an automated highway system (AHS) in light of corresponding operational requirements for existing conventional highways with traffic operations centers (TOCs). Contrasts and similarities between TOC and AHS operations are identified. Maintenance operations and activities are the focus of the study. Similarities and contrasts between AHS and conventional highways are considered, analyzed, and discussed to raise issues risks. Urban/rural, passenger/heavy vehicle, and representative system configuration differences are covered insofar as there are significant differences among these categories of possible AHS operations. Maintenance needs and incident response requirements as they would impact as AHS operating agency are qualitatively analyzed. Two possible staged deployment scenarios for AHS are presented. The fault tolerance of the AHS is assessed. Results of interviews with personnel in charge of several existing TOCs have been summarized. The role of the driver in an AHS is discussed.

  10. Alcohol Induced Alterations to the Human Fecal VOC Metabolome

    PubMed Central

    Couch, Robin D.; Dailey, Allyson; Zaidi, Fatima; Navarro, Karl; Forsyth, Christopher B.; Mutlu, Ece; Engen, Phillip A.; Keshavarzian, Ali

    2015-01-01

    Studies have shown that excessive alcohol consumption impacts the intestinal microbiota composition, causing disruption of homeostasis (dysbiosis). However, this observed change is not indicative of the dysbiotic intestinal microbiota function that could result in the production of injurious and toxic products. Thus, knowledge of the effects of alcohol on the intestinal microbiota function and their metabolites is warranted, in order to better understand the role of the intestinal microbiota in alcohol associated organ failure. Here, we report the results of a differential metabolomic analysis comparing volatile organic compounds (VOC) detected in the stool of alcoholics and non-alcoholic healthy controls. We performed the analysis with fecal samples collected after passage as well as with samples collected directly from the sigmoid lumen. Regardless of the approach to fecal collection, we found a stool VOC metabolomic signature in alcoholics that is different from healthy controls. The most notable metabolite alterations in the alcoholic samples include: (1) an elevation in the oxidative stress biomarker tetradecane; (2) a decrease in five fatty alcohols with anti-oxidant property; (3) a decrease in the short chain fatty acids propionate and isobutyrate, important in maintaining intestinal epithelial cell health and barrier integrity; (4) a decrease in alcohol consumption natural suppressant caryophyllene; (5) a decrease in natural product and hepatic steatosis attenuator camphene; and (6) decreased dimethyl disulfide and dimethyl trisulfide, microbial products of decomposition. Our results showed that intestinal microbiota function is altered in alcoholics which might promote alcohol associated pathologies. PMID:25751150

  11. Alcohol induced alterations to the human fecal VOC metabolome.

    PubMed

    Couch, Robin D; Dailey, Allyson; Zaidi, Fatima; Navarro, Karl; Forsyth, Christopher B; Mutlu, Ece; Engen, Phillip A; Keshavarzian, Ali

    2015-01-01

    Studies have shown that excessive alcohol consumption impacts the intestinal microbiota composition, causing disruption of homeostasis (dysbiosis). However, this observed change is not indicative of the dysbiotic intestinal microbiota function that could result in the production of injurious and toxic products. Thus, knowledge of the effects of alcohol on the intestinal microbiota function and their metabolites is warranted, in order to better understand the role of the intestinal microbiota in alcohol associated organ failure. Here, we report the results of a differential metabolomic analysis comparing volatile organic compounds (VOC) detected in the stool of alcoholics and non-alcoholic healthy controls. We performed the analysis with fecal samples collected after passage as well as with samples collected directly from the sigmoid lumen. Regardless of the approach to fecal collection, we found a stool VOC metabolomic signature in alcoholics that is different from healthy controls. The most notable metabolite alterations in the alcoholic samples include: (1) an elevation in the oxidative stress biomarker tetradecane; (2) a decrease in five fatty alcohols with anti-oxidant property; (3) a decrease in the short chain fatty acids propionate and isobutyrate, important in maintaining intestinal epithelial cell health and barrier integrity; (4) a decrease in alcohol consumption natural suppressant caryophyllene; (5) a decrease in natural product and hepatic steatosis attenuator camphene; and (6) decreased dimethyl disulfide and dimethyl trisulfide, microbial products of decomposition. Our results showed that intestinal microbiota function is altered in alcoholics which might promote alcohol associated pathologies. PMID:25751150

  12. [Induction of rat hepatic CYP2E1 expression by arecoline in vivo].

    PubMed

    Huang, Xiang-tao; Xiao, Run-mei; Wang, Ming-feng; Wang, Jun-jun; Chen, Yong

    2016-01-01

    The regulation mechanism of arecoline on rat hepatic CYP2E1 was studied in vivo. After oral administration of arecoline hydrobromide (AH; 4, 20 and 100 mg x kg(-1) x d(-1)) to rats for one week, the hepatic CYP2E1 mRNA level remained unchanged, but the hepatic CYP2E1 protein content was dose-dependently increased. Additionally, although the hepatic CYP2E1 activity was induced by AH treatment, the induction was attenuated with the increase in dosage. The results indicate that the effect of arecoline on rat hepaticdoes not involve transcriptional activation of the gene, but largely involves the stabilization of CYP2E1 protein against degradation or increased efficiency of CYP2E1 mRNA translation, and additionally involve the post- ranslational modification of CYP2E1 protein. Furthermore, the CYP2E1 response is fairly equal among the different species, the induction of rat hepatic CYP2E1 by arecoline suggests that there is a risk of metabolic interaction among the substrate drugs of CYP2E1 in betel-quid use human. PMID:27405178

  13. Trends in the management and burden of alcoholic liver disease

    PubMed Central

    Mathurin, Philippe; Bataller, Ramon

    2016-01-01

    Summary Alcoholic liver disease (ALD) is the most prevalent cause of advanced liver disease in Europe and is the leading cause of death among adults with excessive alcohol consumption. There is a dose-response relationship between the amount of alcohol consumed and the risk of ALD. The relative risk of cirrhosis increases in subjects who consume more than 25 g/day. The burden of alcohol-attributable liver cirrhosis and liver cancer is high and is entirely preventable. Health agencies should develop population-based policies to reduce the prevalence of harmful and/or hazardous alcohol consumption and foster research in this field to provide new diagnostic and therapeutic tools. Disease progression of patients with ALD is heavily influenced by both genetic and environmental factors. Non-invasive methods for the diagnosis of fibrosis have opened new perspectives in the early detection of advanced ALD in asymptomatic patients. Alcoholic hepatitis, the most severe form of ALD, carries a high short-term mortality (around 30–50% at 3 months). Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis but duration of therapy should be adapted to early response. Liver transplantation is the best option for patients with severe liver dysfunction. However, alcohol relapse after transplantation remains a critical issue and drinking habits of transplanted patients need to be routinely screened. PMID:25920088

  14. Alcohol, Tobacco, and Other Drug Misuse Prevention and Cessation Programming for Alternative High School Youth: A Review

    ERIC Educational Resources Information Center

    Sussman, Steve; Arriaza, Bridget; Grigsby, Timothy J.

    2014-01-01

    Background: Relative to youth in regular high schools, alternative high school (AHS) youth are at high risk for alcohol, tobacco, and other drug (ATOD) misuse. Prevention and cessation efforts are needed for this population. Methods: A systematic, exhaustive literature search was completed to identify ATOD misuse prevention and cessation research…

  15. Effects of N-acetylcysteine on alcohol abstinence and alcohol-induced adverse effects in rats.

    PubMed

    Ferreira Seiva, Fábio Rodrigues; Amauchi, Juliana Fujihara; Ribeiro Rocha, Katiucha Karolina; Souza, Gisele Aparecida; Ebaid, Geovana Xavier; Burneiko, Regina Miranda; Novelli, Ethel Lourenzi Barbosa

    2009-03-01

    Alcoholism is rampant in modern society and some antioxidant compound could perhaps be useful to reduce the damage done by alcohol consumption and abstinence. The present study was undertaken to investigate the association of N-acetylcysteine (NAC) intake, alcoholism, and alcohol abstinence on lipid profile, in vivo low-density lipoprotein (LDL) oxidation, oxidative stress, and antioxidant status in serum and liver of rats. Initially, male Wistar 30 rats were divided into two groups: (C, N=6) given standard chow and water; (E, N=24) receiving standard chow and aqueous ethanol solution in semi-voluntary research. After 30 days of ethanol exposure, (E) group was divided into four subgroups (N=6/group): (E-E) continued drinking 30% ethanol solution; (E-NAC) drinking ethanol solution containing 2 g/L NAC; (AB) changed ethanol solution to water; (AB-NAC) changed ethanol to aqueous solution 2 g/L NAC. After 15 days of the E-group division, E-E rats had higher serum alanine transaminase, lower body weight, and surface area, despite higher energy intake than C. E-E rats had also lower feed efficiency, dyslipidemia with enhanced triacylglycerol, very low-density lipoprotein (VLDL), lipid hydroperoxide (LH) and in vivo oxidized-LDL (ox-LDL). AB, E-NAC, and AB-NAC rats ameliorated serum oxidative stress markers and normalized serum lipids. E-E rats had higher hepatic LH and lower reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio than C, indicating hepatic oxidative stress. AB and E-NAC rats normalized hepatic LH, GSSG, and the GSH/GSSG ratio, compared to E-E. AB-NAC rats had the lowest serum ox-LDL, hepatic LH levels, and the highest GSH reductase activity in hepatic tissue. In conclusion, the present study brought new insights into alcohol consumption, because ethanol exposure enhanced serum in vivo ox-LDL, as well as serum and hepatic oxidative stress. N-acetylcysteine offers promising therapeutic value to inhibit ethanol-induced adverse effects. Ethanol

  16. Hepatic abscesses

    PubMed Central

    Rajagopalan, S.; Langer, V.

    2012-01-01

    Hepatic abscesses are potentially lethal diseases if early diagnosis and treatment are not instituted. They are prevalent all over the globe and pyogenic abscesses are predominant over amoebic. With better control of intra abdominal and systemic infections by a spectrum of antibiotics, aetiology of pyogenic abscesses are secondary to interventions and diseases in the biliary tree to a large extent today. The common organisms isolated are the Gram negative group. Amoebic abscesses continue to plague some regions of the world where hygiene and sanitation are questionable. Over the years, diagnosis, treatment and prognosis have evolved remarkably. Imaging modalities like ultrasonography and CT scan have become the cornerstone of diagnosis. The absence of ionizing radiation makes MRI an attractive alternative in patients who require multiple follow up scans. Serological testing in amoebic abscesses has become more reliable. Though antibiotics have remained the principal modality of management, percutaneous drainage of abscesses have vastly improved the chances of cure and bring down the morbidity drastically in pyogenic abscesses. Amoebic abscesses respond well to medical treatment with nitroimidazoles, and minimally invasive surgical drainage is an option in cases where open surgery is indicated. PMID:24532886

  17. Hepatitis A - children

    MedlinePlus

    ... hepatitis A. Children can get hepatitis A at day care center from other children or from child care ... treatment with immunoglobulin therapy. If your child attends day care: Make sure the children and staff at the ...

  18. Hepatitis B Test

    MedlinePlus

    ... IgM; anti-HBe; Hepatitis B e Antibody; HBV DNA Formal name: Hepatitis B Virus Testing Related tests: ... produced by the virus, and others detect viral DNA . The main uses for HBV tests include: To ...

  19. Hepatitis C (image)

    MedlinePlus

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

  20. [Alcohol and alcoholism: attitudes of nursing students].

    PubMed

    Vargas, Divane; Bittencourt, Marina Nolli

    2013-01-01

    This is a descriptive exploratory study that aimed to verify nursing students' attitudes facing to the alcoholic drinks, alcoholism and alcoholics, according to their position in face of an attitudes scale items. For data collection, it was used the Scale of Attitudes to alcohol, alcoholism and alcoholic, applied to 144 nursing students. The results showed a tendency to negative attitudes of these students in face of alcoholism, alcoholic person and alcoholic drinks, since most participants were placed in category indifferent or disagree with the positive items, agreeing with negative scale items. We conclude that this trend of negative attitudes is connected to insufficient attention given to the subject during the nurses' education, being verified the need for greater importance to be given to this problem.

  1. Impact of PPAR-α induction on glucose homoeostasis in alcohol-fed mice.

    PubMed

    Lebrun, Valérie; Molendi-Coste, Olivier; Lanthier, Nicolas; Sempoux, Christine; Cani, Patrice D; van Rooijen, Nico; Stärkel, Peter; Horsmans, Yves; Leclercq, Isabelle A

    2013-12-01

    Alcohol consumption is a major cause of liver disease. It also associates with increased cardiovascular risk and Type 2 diabetes. ALD (alcoholic liver disease) and NAFLD (non-alcoholic fatty liver disease) share pathological features, pathogenic mechanisms and pattern of disease progression. In NAFLD, steatosis, lipotoxicity and liver inflammation participate to hepatic insulin resistance. The aim of the present study was to verify the effect of alcohol on hepatic insulin sensitivity and to evaluate the role of alcohol-induced steatosis and inflammation on glucose homoeostasis. C57BL/6J mice were fed for 20 days a modified Lieber-DeCarli diet in which the alcohol concentration was gradually increased up to 35% of daily caloric intake. OH (alcohol liquid diet)-fed mice had liver steatosis and inflammatory infiltration. In addition, these mice developed insulin resistance in the liver, but not in muscles, as demonstrated by euglycaemic-hyperinsulinaemic clamp and analysis of the insulin signalling cascade. Treatment with the PPAR-α (peroxisome-proliferator-activated receptor-α) agonist Wy14,643 protected against OH-induced steatosis and KC (Kupffer cell) activation and almost abolished OH-induced insulin resistance. As KC activation may modulate insulin sensitivity, we repeated the clamp studies in mice depleted in KC to decipher the role of macrophages. Depletion of KC using liposomes-encapsuled clodronate in OH-fed mice failed both to improve hepatic steatosis and to restore insulin sensitivity as assessed by clamp. Our study shows that chronic alcohol consumption induces steatosis, KC activation and hepatic insulin resistance in mice. PPAR-α agonist treatment that prevents steatosis and dampens hepatic inflammation also prevents alcohol-induced hepatic insulin resistance. However, KC depletion has little impact on OH-induced metabolic disturbances.

  2. Induction of human UGT1A1 by bilirubin through AhR dependent pathway.

    PubMed

    Togawa, Hiroshi; Shinkai, Shigeko; Mizutani, Takaharu

    2008-12-01

    UDP-glucuronosyltransferase1A1 (UGT1A1) plays a key role to conjugate bilirubin and preventing jaundice, but there is no report showing the induction of human UGT1A1 (UGT1A1) by bilirubin. In this report, we show findings of the induction of the reporter gene (-3475/+14) of UGT1A1 in HepG2 cells by bilirubin at 50 microM, 100 microM, with human aryl hydrocarbon receptor (hAhR). We confirmed that induction of the reporter gene by bilirubin is dependent on the position of the xenobiotic responsive element (XRE) (-3328/-3319) of UGT1A1, because the XRE deletion UGT1A1 gene did not respond to stimulation by a complex of bilirubin and hAhR. alpha-Naphthoflavone (alpha-NF) of a typical AhR antagonist at 50 microM inhibited induction by bilirubin, suggesting that bilirubin stimulates through binding with hAhR. Meanwhile, bilirubin itself did not stimulate the induction of AhR, because we detected no-elevation of the mRNA level of AhR by RT-PCR. These results indicate that the induction of UGT1A1 by bilirubin-AhR did not depend on the elevation of AhR but on ligand binding. From this result, we considered that high bilirubin in neonates must induce the elevation of UGT1A1 after birth to prevent jaundice, and bilirubin in adults also regulates the level of UGT1A1. This is the first report showing direct induction of UGT1A1 by a bilirubin through AhR pathway. PMID:19356098

  3. Hepatitis E Pathogenesis

    PubMed Central

    Lhomme, Sébastien; Marion, Olivier; Abravanel, Florence; Chapuy-Regaud, Sabine; Kamar, Nassim; Izopet, Jacques

    2016-01-01

    Although most hepatitis E virus (HEV) infections are asymptomatic, some can be severe, causing fulminant hepatitis and extra-hepatic manifestations, including neurological and kidney injuries. Chronic HEV infections may also occur in immunocompromised patients. This review describes how our understanding of the pathogenesis of HEV infection has progressed in recent years. PMID:27527210

  4. Hepatitis B (HBV)

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Hepatitis B (HBV) KidsHealth > For Teens > Hepatitis B (HBV) Print A A A Text Size ... Prevented? How Is It Treated? What Is It? Hepatitis (pronounced: hep-uh-TIE-tiss) is a disease ...

  5. Hepatitis E Pathogenesis.

    PubMed

    Lhomme, Sébastien; Marion, Olivier; Abravanel, Florence; Chapuy-Regaud, Sabine; Kamar, Nassim; Izopet, Jacques

    2016-01-01

    Although most hepatitis E virus (HEV) infections are asymptomatic, some can be severe, causing fulminant hepatitis and extra-hepatic manifestations, including neurological and kidney injuries. Chronic HEV infections may also occur in immunocompromised patients. This review describes how our understanding of the pathogenesis of HEV infection has progressed in recent years. PMID:27527210

  6. Immune mechanisms in alcoholic liver disease

    PubMed Central

    Vidali, Matteo

    2009-01-01

    Growing evidence indicates that inflammatory reactions play an important role in the pathogenesis of alcoholic liver disease (ALD). The implication of immunity in fueling chronic inflammation in ALD has emerged from clinical and experimental evidence showing the recruitment and the activation of lymphocytes in the inflammatory infiltrates of ALD and has received further support by the recent demonstration of a role of Th17 lymphocytes in alcoholic hepatitis. Nonetheless, the mechanisms by which alcohol triggers adaptive immune responses are still incompletely characterized. Patients with advanced ALD show a high prevalence of circulating IgG and T-lymphocytes towards epitopes derived from protein modification by hydroxyethyl free radicals (HER) and end-products of lipid peroxidation. In both chronic alcohol-fed rats and heavy drinkers the elevation of IgG against lipid peroxidation-derived antigens is associated with an increased production of pro-inflammatory cytokines/chemokines and with the severity of histological signs of liver inflammation. Moreover, CYP2E1-alkylation by HER favors the development of anti-CYP2E1 auto-antibodies in a sub-set of ALD patients. Altogether, these results suggest that allo- and auto-immune reactions triggered by oxidative stress might contribute to fuel chronic hepatic inflammation during the progression of ALD. PMID:19809845

  7. Challenges in transplantation for alcoholic liver disease.

    PubMed

    Berlakovich, Gabriela A

    2014-07-01

    Transplantation for the treatment of alcoholic cirrhosis is more controversially discussed than it is for any other indication. The crucial aspect in this setting is abstinence before and after liver transplantation. We established pre-transplant selection criteria for potential transplant candidates. Provided that the underlying disease can be treated, there is no reason to withhold liver transplantation in a patient suffering from alcoholic cirrhosis. Evaluation of the patient by a multidisciplinary team, including an addiction specialist, is considered to be the gold standard. However, several centers demand a specified period of abstinence - usually 6 mo- irrespective of the specialist's assessment. The 6-mo rule is viewed critically because liver transplantation was found to clearly benefit selected patients with acute alcoholic hepatitis; the benefit was similar to that achieved for other acute indications. However, the discussion may well be an academic one because the waiting time for liver transplantation exceeds six months at the majority of centers. The actual challenge in liver transplantation for alcoholic cirrhosis may well be the need for lifelong post-transplant follow-up rather than the patient's pre-transplant evaluation. A small number of recipients experience a relapse of alcoholism; these patients are at risk for organ damage and graft-related death. Post-transplant surveillance protocols should demonstrate alcohol relapse at an early stage, thus permitting the initiation of adequate treatment. Patients with alcoholic cirrhosis are at high risk of developing head and neck, esophageal, or lung cancer. The higher risk of malignancies should be considered in the routine assessment of patients suffering from alcoholic cirrhosis. Tumor surveillance protocols for liver transplant recipients, currently being developed, should become a part of standard care; these will improve survival by permitting diagnosis at an early stage. In conclusion, the key

  8. The 50 Ah NiH2 CPV qualification tests

    NASA Technical Reports Server (NTRS)

    Garner, J. C.; Barnes, Wilbert L.; Hickman, Gary L.

    1995-01-01

    In 1992, the Naval Research Laboratory (NRL) started a program to qualify a large diameter common pressure vessel (CPV) nickel-hydrogen (NiH2) batteries for use on future Navy/NRL spacecraft electrical power subsystems. NRL's involvement with the qualification of CPV NiH2 batteries dates back to 1988 when COMSAT and Johnson Controls, Inc. initiated a joint effort to fly the first ever NiH2 CPV in space. A later NRL-JCI cooperative research and development agreement led to the launch of a space experiment in 1993 and to the use of a single NiH2 CPV battery on the BMDO Clementine spacecraft in 1994. NRL initiated procurement of two, 50 Ah CPV NiH2 batteries in the Fall of 1992. The two batteries were delivered to NRL in June 1994. NiH2 CPV batteries have almost 2x the specific energy (Wh/kg) of nickel cadium batteries and 2x the energy density (Wh/l) of individual pressure vessel NiH2 CPV's. This presentation discusses the results of electrical and mechanical qualification tests conducted at NRL. The tests included electrical characterization, standard capacity, random vibration, peak load, and thermal vacuum. The last slides of the presentation show initial results from the life cycle tests of the second NiH2 CPV battery at 40% depth of discharge and a temperature of 10 C.

  9. The 50 Ah NiH2 CPV qualification tests

    NASA Astrophysics Data System (ADS)

    Garner, J. C.; Barnes, Wilbert L.; Hickman, Gary L.

    1995-02-01

    In 1992, the Naval Research Laboratory (NRL) started a program to qualify a large diameter common pressure vessel (CPV) nickel-hydrogen (NiH2) batteries for use on future Navy/NRL spacecraft electrical power subsystems. NRL's involvement with the qualification of CPV NiH2 batteries dates back to 1988 when COMSAT and Johnson Controls, Inc. initiated a joint effort to fly the first ever NiH2 CPV in space. A later NRL-JCI cooperative research and development agreement led to the launch of a space experiment in 1993 and to the use of a single NiH2 CPV battery on the BMDO Clementine spacecraft in 1994. NRL initiated procurement of two, 50 Ah CPV NiH2 batteries in the Fall of 1992. The two batteries were delivered to NRL in June 1994. NiH2 CPV batteries have almost 2x the specific energy (Wh/kg) of nickel cadium batteries and 2x the energy density (Wh/l) of individual pressure vessel NiH2 CPV's. This presentation discusses the results of electrical and mechanical qualification tests conducted at NRL. The tests included electrical characterization, standard capacity, random vibration, peak load, and thermal vacuum. The last slides of the presentation show initial results from the life cycle tests of the second NiH2 CPV battery at 40% depth of discharge and a temperature of 10 C.

  10. Non-dioxin-like AhR ligands in a mouse peanut allergy model.

    PubMed

    Schulz, Veronica J; Smit, Joost J; Huijgen, Veerle; Bol-Schoenmakers, Marianne; van Roest, Manon; Kruijssen, Laura J W; Fiechter, Daniëlle; Hassing, Ine; Bleumink, Rob; Safe, Stephen; van Duursen, Majorie B M; van den Berg, Martin; Pieters, Raymond H H

    2012-07-01

    Recently, we have shown that AhR activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppresses sensitization to peanut at least in part by inducing a functional shift toward CD4(+)CD25(+)Foxp3(+) T cells. Next to TCDD, numerous other AhR ligands have been described. In this study, we investigated the effect of three structurally different non-dioxin-like AhR ligands, e.g., 6-formylindolo[3,2-b]carbazole (FICZ), β-naphthoflavone (β-NF), and 6-methyl-1,3,8-trichlorodibenzofuran (6-MCDF), on peanut sensitization. Female C57BL/6 mice were sensitized by administering peanut extract (PE) by gavage in the presence of cholera toxin. Before and during peanut sensitization, mice were treated with FICZ, β-NF, or 6-MCDF. AhR gene transcription in duodenum and liver was investigated on day 5, even as the effect of these AhR ligands on CD4(+)CD25(+)Foxp3(+) T(reg) cells in spleen and mesenteric lymph nodes (MLNs). Mice treated with TCDD were included as a positive control. Furthermore, the murine reporter cell line H1G1.1c3 (CAFLUX) was used to investigate the possible role of metabolism of TCDD, FICZ, β-NF, and 6-MCDF on AhR activation in vitro. TCDD, but not FICZ, β-NF, and 6-MCDF, suppressed sensitization to peanut (measured by PE-specific IgE, IgG1, IgG2a and PE-induced interleukin (IL)-5, IL-10, IL-13, IL-17a, IL-22, and interferon-γ). In addition, FICZ, β-NF, and 6-MCDF treatments less effectively induced AhR gene transcription (measured by gene expression of AhR, AhRR, CYP1A1, CYP1A2, CYP1B1) compared with TCDD-treated mice. Furthermore, FICZ, β-NF and 6-MCDF did not increase the percentage of CD4(+)CD25(+)Foxp3(+) T(reg) cells in spleen and mesenteric lymph nodes compared with PE-sensitized mice, in contrast to TCDD. Inhibition of metabolism in vitro increased AhR activation. Together, these data shows that TCDD, but not FICZ, β-NF, and 6-MCDF suppresses sensitization to peanut. Differences in metabolism, AhR binding and subsequent gene transcription might

  11. Behind the Label "Alcoholic."

    ERIC Educational Resources Information Center

    Wright, Deborah M.

    1989-01-01

    Relates individual's personal story of her childhood influenced by her parent's alcoholism, her own alcoholism as a young adult, and her experiences with counseling. Asks others not to reject her because of the label "alcoholic." (ABL)

  12. Breath alcohol test

    MedlinePlus

    Alcohol test - breath ... There are various brands of breath alcohol tests. Each one uses a different method to test the level of alcohol in the breath. The machine may be electronic or manual. One ...

  13. Enhancement of hypoxia-induced gene expression in fish liver by the aryl hydrocarbon receptor (AhR) ligand, benzo[a]pyrene (BaP).

    PubMed

    Yu, Richard Man Kit; Ng, Patrick Kwok Shing; Tan, Tianfeng; Chu, Daniel Ling Ho; Wu, Rudolf Shiu Sun; Kong, Richard Yuen Chong

    2008-11-21

    Fish in polluted coastal habitats commonly suffer simultaneous exposure to both hypoxia and xenobiotics. Although the adaptive molecular responses to each stress have been described, little is known about the interaction between the signaling pathways mediating these responses. Previous studies in mammalian hepatoma cell lines have shown that hypoxia-inducible factor (HIF)- and/or aryl hydrocarbon receptor (AhR)-activated gene expression is suppressed following co-exposure to hypoxia and the hallmark AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, whether similar crosstalk exists in the non-tumor liver tissues of fish and whether other non-TCDD ligands also play the same inhibitory role in this crosstalk remain unknown. Here, the in vivo hepatic mRNA expression profiles of multiple hypoxia- and AhR-responsive genes (later gene expression=mRNA expression of the gene) were examined in the orange-spotted grouper (Epinephelus coioides) upon single and combined exposures to hypoxia and benzo[a]pyrene (BaP). Combined exposure enhanced hypoxia-induced gene expression but did not significantly alter BaP-induced gene expression. Protein carbonyl content was markedly elevated in fish subjected to combined exposure, indicating accumulation of reactive oxygen species (ROS). Application of diethyldithiocarbamate (DDC) to hypoxia-treated grouper liver explants similarly exaggerated hypoxia-induced gene expression as in the combined stress tissues in vivo. These observations suggest that ROS derived from the combined hypoxia and BaP stress have a role in enhancing hypoxia-induced gene expression.

  14. [Treatment of alcoholic liver diseases. Abstinence, nutritional support, drug therapy, liver transplantation].

    PubMed

    Pár, A

    2000-04-16

    The review summarizes clinically established treatment forms of alcoholic liver disease in four main chapters: abstinence, nutritional supportation, drug therapy and liver transplantation are discussed. Drug therapy is described according to the three types of alcoholic hepatopathies (fatty liver, hepatitis and cirrhosis). Early diagnosis and treatment depending on the severity and stage of alcoholic liver disease are of importance for the attempts to retard progression and improve prognosis. PMID:10817009

  15. Alteration of human hepatic drug transporter activity and expression by cigarette smoke condensate.

    PubMed

    Sayyed, Katia; Vee, Marc Le; Abdel-Razzak, Ziad; Jouan, Elodie; Stieger, Bruno; Denizot, Claire; Parmentier, Yannick; Fardel, Olivier

    2016-07-01

    Smoking is well-known to impair pharmacokinetics, through inducing expression of drug metabolizing enzymes. In the present study, we demonstrated that cigarette smoke condensate (CSC) also alters activity and expression of hepatic drug transporters, which are now recognized as major actors of hepatobiliary elimination of drugs. CSC thus directly inhibited activities of sinusoidal transporters such as OATP1B1, OATP1B3, OCT1 and NTCP as well as those of canalicular transporters like P-glycoprotein, MRP2, BCRP and MATE1, in hepatic transporters-overexpressing cells. CSC similarly counteracted constitutive OATP, NTCP and OCT1 activities in human highly-differentiated hepatic HepaRG cells. In parallel, CSC induced expression of BCRP at both mRNA and protein level in HepaRG cells, whereas it concomitantly repressed mRNA expression of various transporters, including OATP1B1, OATP2B1, OAT2, NTCP, OCT1 and BSEP, and enhanced that of MRP4. Such changes in transporter gene expression were found to be highly correlated to those caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin, a reference activator of the aryl hydrocarbon receptor (AhR) pathway, and were counteracted, for some of them, by siRNA-mediated AhR silencing. This suggests that CSC alters hepatic drug transporter levels via activation of the AhR cascade. Importantly, drug transporter expression regulations as well as some transporter activity inhibitions occurred for a range of CSC concentrations similar to those required for inducing drug metabolizing enzymes and may therefore be hypothesized to be relevant for smokers. Taken together, these data established human hepatic transporters as targets of cigarette smoke, which could contribute to known alteration of pharmacokinetics and some liver adverse effects caused by smoking. PMID:27450509

  16. Pathogenesis of Hepatic Encephalopathy

    PubMed Central

    Ciećko-Michalska, Irena; Szczepanek, Małgorzata; Słowik, Agnieszka; Mach, Tomasz

    2012-01-01

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

  17. Avian Influenza A(H5N1) and A(H9N2) Seroprevalence and Risk Factors for Infection Among Egyptians: A Prospective, Controlled Seroepidemiological Study

    PubMed Central

    Gomaa, Mokhtar R.; Kayed, Ahmed S.; Elabd, Mona A.; Zeid, Dina Abu; Zaki, Shaimaa A.; El Rifay, Amira S.; Sherif, Lobna S.; McKenzie, Pamela P.; Webster, Robert G.; Webby, Richard J.; Ali, Mohamed A.; Kayali, Ghazi

    2015-01-01

    Background. A(H5N1) and A(H9N2) avian influenza viruses are enzootic in Egyptian poultry, and most A(H5N1) human cases since 2009 have occurred in Egypt. Our understanding of the epidemiology of avian viruses in humans remains limited. Questions about the frequency of infection, the proportion of infections that are mild or subclinical, and the case-fatality rate remain largely unanswered. Methods. We conducted a 3-year, prospective, controlled, seroepidemiological study that enrolled 750 poultry-exposed and 250 unexposed individuals in Egypt. Results. At baseline, the seroprevalence of anti-A(H5N1) antibodies (titer, ≥80) among exposed individuals was 2% significantly higher than that among the controls (0%). Having chronic lung disease was a significant risk factor for infection. Antibodies against A(H9N2) were not detected at baseline when A(H9N2) was not circulating in poultry. At follow-up, A(H9N2) was detected in poultry, and consequently, the seroprevalence among exposed humans was between 5.6% and 7.5%. Vaccination of poultry, older age, and exposure to ducks were risk factors for A(H9N2) infection. Conclusions. Results of this study indicate that the number of humans infected with avian influenza viruses is much larger than the number of reported confirmed cases. In an area where these viruses are enzootic in the poultry, human exposure to and infection with avian influenza becomes more common. PMID:25355942

  18. Toll-like receptors in alcoholic liver disease, non-alcoholic steatohepatitis and carcinogenesis.

    PubMed

    Roh, Yoon Seok; Seki, Ekihiro

    2013-08-01

    Activation of innate immune systems including Toll-like receptor (TLR) signaling is a key in chronic liver disease. Recent studies suggest that gut microflora-derived bacterial products (i.e. lipopolysaccharide [LPS], bacterial DNA) and endogenous substances (i.e. high-mobility group protein B1 [HMGB1], free fatty acids) released from damaged cells activate hepatic TLRs that contribute to the development of alcoholic (ASH) and non-alcoholic steatohepatitis (NASH) and liver fibrosis. The crucial role of TLR4, a receptor for LPS, has been implicated in the development of ASH, NASH, liver fibrosis, and hepatocellular carcinoma. However, the role of other TLRs, such as TLR2 and TLR9 in chronic liver disease remains less clear. In this review, we will discuss the role of TLR2, 4, and 9 in Kupffer cells and hepatic stellate cells in the development of ASH, NASH, and hepatocarcinogenesis. PMID:23855294

  19. Hepatitis: protecting BMETs & CEs.

    PubMed

    Baker, S A

    1994-01-01

    Hepatitis is the primary occupational hazard for healthcare workers. Not until the 1970s were hepatitis viruses isolated and identified as types A and B. In the late 1970s, hepatitis D was discovered as a major cause of fulminant hepatitis. Soon, it was evident that another type was also at work. Because testing was only available for types A and B, the new category was referred to as non-A, non-B. In the 1980s, scientists identified two more viruses from this non-A, non-B group, namely hepatitis E and hepatitis C. These five types of hepatitis have different modes of transmission. The fecal-to-oral route is the mode of transmission for hepatitis types A and E. But, types B and D are bloodborne pathogens. With the advent of a safe vaccine for hepatitis B, this category is declining. To date, hepatitis C appears to have multiple routes of transmission, with half the cases being posttransfusion. In the United States, 85,000 people per year develop chronic hepatitis C, which ultimately leads to severe liver damage. This paper addresses each of the five viruses that have been grouped by routes of transmission, prevention techniques for BMETs and CEs, and statistics of reported cases to the Centers for Disease Control and Prevention (CDCP) over the last 20 years. PMID:10139739

  20. Protective effect of heat-treated cucumber (Cucumis sativus L.) juice on alcohol detoxification in experimental rats.

    PubMed

    Bajpai, Vivek K; Kim, Na-Hyung; Kim, Ji-Eun; Kim, Kangmin; Kang, Sun Chul

    2016-05-01

    In this study, heat-treated cucumber juice was assessed for its protective effect on blood alcohol levels and hepatic alcohol metabolic enzyme system in experimental rats. Initially, during detoxification of alcohol, all groups were orally dosed to 22% alcohol (6ml/kg body weight) along with different concentrations of heat-treated cucumber juice (10, 100 and 500mg/kg) and commercial goods for hangover-removal on sale (2ml/kg). Cucumber juice was dosed before 30 min, and simultaneously after 30min of alcohol administration, and its hepatoprotective effect on blood alcohol levels and hepatic alcohol metabolic enzyme system in experimental rats was evaluated. As a result, after 7h, remarkable reduction was found in the blood alcohol levels for all concentrations of cucumber juice treatment. Treatment with cucumber juice resulted in increasing dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) enzymatic activities in rat liver at 9h after alcohol administration thereby stimulated blood alcohol metabolism as compared with control group. The effect of heat-treated cucumber juice on alcohol detoxification was observed only in the rats treated before 30min from alcohol administration. These findings indicate that heat-treated cucumber juice has significant protective effect on alcohol detoxification in experimental rats, suggesting its usefulness in the treatment of liver injury caused by alcohol consumption.

  1. Protective effect of heat-treated cucumber (Cucumis sativus L.) juice on alcohol detoxification in experimental rats.

    PubMed

    Bajpai, Vivek K; Kim, Na-Hyung; Kim, Ji-Eun; Kim, Kangmin; Kang, Sun Chul

    2016-05-01

    In this study, heat-treated cucumber juice was assessed for its protective effect on blood alcohol levels and hepatic alcohol metabolic enzyme system in experimental rats. Initially, during detoxification of alcohol, all groups were orally dosed to 22% alcohol (6ml/kg body weight) along with different concentrations of heat-treated cucumber juice (10, 100 and 500mg/kg) and commercial goods for hangover-removal on sale (2ml/kg). Cucumber juice was dosed before 30 min, and simultaneously after 30min of alcohol administration, and its hepatoprotective effect on blood alcohol levels and hepatic alcohol metabolic enzyme system in experimental rats was evaluated. As a result, after 7h, remarkable reduction was found in the blood alcohol levels for all concentrations of cucumber juice treatment. Treatment with cucumber juice resulted in increasing dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) enzymatic activities in rat liver at 9h after alcohol administration thereby stimulated blood alcohol metabolism as compared with control group. The effect of heat-treated cucumber juice on alcohol detoxification was observed only in the rats treated before 30min from alcohol administration. These findings indicate that heat-treated cucumber juice has significant protective effect on alcohol detoxification in experimental rats, suggesting its usefulness in the treatment of liver injury caused by alcohol consumption. PMID:27383492

  2. Vitamin-Dependent Methionine Metabolism and Alcoholic Liver Disease1

    PubMed Central

    Halsted, Charles H.; Medici, Valentina

    2011-01-01

    Emerging evidence indicates that ethanol-induced alterations in hepatic methionine metabolism play a central role in the pathogenesis of alcoholic liver disease (ALD). Because malnutrition is a universal clinical finding in this disease and hepatic methionine metabolism is dependent upon dietary folate and vitamins B-6 and B-12, ALD can be considered an induced nutritional disorder that is conditioned by alcohol abuse. The present review describes the etiologies of these 3 vitamin deficiencies in ALD and how they interact with chronic ethanol exposure to alter hepatic methionine metabolism. Subsequent sections focus on molecular mechanisms for the interactions of aberrant methionine metabolism with ethanol in the pathogenesis of ALD, in particular the role of S-adenosylmethionine (SAM) in regulating the epigenetic expressions of genes relevant to pathways of liver injury. The review will conclude with descriptions of studies on the efficacy of SAM in the treatment of ALD and with discussion of potentially fruitful future avenues of research. PMID:22332083

  3. Identification and expression of aryl hydrocarbon receptors (AhR1 and AhR2) provide insight in an evolutionary context regarding sensitivity of white sturgeon (Acipenser transmontanus) to dioxin-like compounds.

    PubMed

    Doering, Jon A; Wiseman, Steve; Beitel, Shawn C; Giesy, John P; Hecker, Markus

    2014-05-01

    Sturgeons are ancient fishes, which are endangered in many parts of the world. Due to their benthic nature and longevity, sturgeon are at great risk of exposure to bioaccumulative contaminants such as dioxin-like compounds (DLCs). Despite their endangered status, little research has been conducted to characterize the relative sensitivity of sturgeons to DLCs. Proper assessment of risk of DLCs posed to these fishes therefore, requires a better understanding of this sensitivity and the factors that are driving it. Adverse effects associated with exposure to DLCs are mediated by the aryl hydrocarbon receptor (AhR). This study identified and characterized two distinct AhRs, AhR1 and AhR2, in white sturgeon (Acipenser transmontanus) for the first time as a first step in studying the relative sensitivities of sturgeons to DLCs. Furthermore, tissue-specific expression of both AhRs under basal conditions and in response to exposure to the model DLC, β-naphthoflavone (βNF), was determined. The sequence of amino acids of AhR1 of white sturgeon had greater similarity to AhRs of tetrapods, including amphibians, birds, and mammals, than to AhR1s of other fishes. The sequence of amino acids in the ligand binding domain of the AhR1 had greater than 80% similarity to AhRs known to bind DLCs and was less similar to AhRs not known to bind DLCs. AhR2 of white sturgeon had greatest similarity to AhR2 of other fishes. Profiles of expression of AhR1 and AhR2 in white sturgeon were distinct from those known in other fishes and appear more similar to profiles observed in birds. Expressions of both AhR1 and AhR2 of white sturgeon were greatest in liver and heart, which are target organs for DLCs. Furthermore, abundances of transcripts of AhR1 and AhR2 in all tissues from white sturgeon were greater than controls (up to 35-fold) following exposure to βNF. Based upon both AhRs having similar abundances of transcript in target organs of DLC toxicity, both AhRs being up-regulated following

  4. Identification and expression of aryl hydrocarbon receptors (AhR1 and AhR2) provide insight in an evolutionary context regarding sensitivity of white sturgeon (Acipenser transmontanus) to dioxin-like compounds.

    PubMed

    Doering, Jon A; Wiseman, Steve; Beitel, Shawn C; Giesy, John P; Hecker, Markus

    2014-05-01

    Sturgeons are ancient fishes, which are endangered in many parts of the world. Due to their benthic nature and longevity, sturgeon are at great risk of exposure to bioaccumulative contaminants such as dioxin-like compounds (DLCs). Despite their endangered status, little research has been conducted to characterize the relative sensitivity of sturgeons to DLCs. Proper assessment of risk of DLCs posed to these fishes therefore, requires a better understanding of this sensitivity and the factors that are driving it. Adverse effects associated with exposure to DLCs are mediated by the aryl hydrocarbon receptor (AhR). This study identified and characterized two distinct AhRs, AhR1 and AhR2, in white sturgeon (Acipenser transmontanus) for the first time as a first step in studying the relative sensitivities of sturgeons to DLCs. Furthermore, tissue-specific expression of both AhRs under basal conditions and in response to exposure to the model DLC, β-naphthoflavone (βNF), was determined. The sequence of amino acids of AhR1 of white sturgeon had greater similarity to AhRs of tetrapods, including amphibians, birds, and mammals, than to AhR1s of other fishes. The sequence of amino acids in the ligand binding domain of the AhR1 had greater than 80% similarity to AhRs known to bind DLCs and was less similar to AhRs not known to bind DLCs. AhR2 of white sturgeon had greatest similarity to AhR2 of other fishes. Profiles of expression of AhR1 and AhR2 in white sturgeon were distinct from those known in other fishes and appear more similar to profiles observed in birds. Expressions of both AhR1 and AhR2 of white sturgeon were greatest in liver and heart, which are target organs for DLCs. Furthermore, abundances of transcripts of AhR1 and AhR2 in all tissues from white sturgeon were greater than controls (up to 35-fold) following exposure to βNF. Based upon both AhRs having similar abundances of transcript in target organs of DLC toxicity, both AhRs being up-regulated following

  5. AHS and CASI Processing for the REFLEX Remote Sensing Campaign: Methods and Results

    NASA Astrophysics Data System (ADS)

    De Miguel, Eduardo; Jiménez, Marcos; Pérez, Irene; de la Cámara, Óscar G.

    2015-12-01

    The airborne spectroradiometers AHS and CASI were used as a source of hyperspectral and thermal remote sensing data during the REFLEX campaign. Data geolocation and a first simple atmospheric correction was performed by INTA in near-real time with a specific on-site setup and distributed to all campaign participants. In this paper we present briefly the AHS and CASI REFLEX flight campaign followed by a detailed description of the methodology used for image processing and finally the results obtained in terms of image quality. As a conclusion, near-real time processing for AHS and CASI level 1 geolocated products was successful as most of CASI level 2 results but further work is needed for achieving accurate AHS level 2 products.

  6. Activation of AhR-mediated toxicity pathway by emerging pollutants polychlorinated diphenyl sulfides

    EPA Science Inventory

    Polychlorinated diphenyl sulfides (PCDPSs) are a group of environmental pollutants for which limited toxicological information is available. This study tested the hypothesis that PCDPSs could activate the mammalian aryl hydrocarbon receptor (AhR) mediated toxicity pathways. Eight...

  7. The 50Ah NiH2 cell life test results

    NASA Technical Reports Server (NTRS)

    Jamin, Thierry; Puig, Olivier

    1992-01-01

    Information is given in viewgraph form for the 50 AhNiH2 cell life test results. Information is given on pressure vessel design, electrochemical/stack design, cell electrical characteristics, and cell life test results.

  8. Health risks of alcohol use

    MedlinePlus

    Alcoholism - risks; Alcohol abuse - risks; Alcohol dependence - risks; Risky drinking ... Beer, wine, and liquor all contain alcohol. If you are drinking any of these, you are using alcohol. Your drinking patterns may vary, depending on who you are with ...

  9. Histogenesis of alcoholic fibrosis and cirrhosis in the baboon.

    PubMed

    Popper, H; Lieber, C S

    1980-03-01

    Sequential liver specimens of 18 baboons exposed for up to 6 years to alcohol on a nutritionally adequate diet, as well as those of pair-fed controls, were examined by light microscopy. Whereas control animals failed to develop pathologic changes, in all baboons exposed, ethanol produced initial steatosis and subsequently fibrosis. Emphasis was on the pattern of the fiber accumulations as related to lesions of the hepatocytes. Segmented neutrophilic leukocytes were rarely observed, and the picture of frank alcoholic hepatitis was absent, but diffusely increased mononuclear sinusoidal cells and interstitial clusters of such cells with PAS-positive macrophages were abundant. Fibrosis proceeding to septum formation was associated mainly with large-droplet steatosis. Septum formation was initiated by excess layers of reticulin around steatotic hepatocytes or, more frequently, by linking of fiber accumulations around the clusters of mononuclear cells, in both instances with subsequent deposition of collagen fibers. Both processes were prominent in the centrolobular zone, creating a perivenous net-like fibrosis, but septum formation also started within the lobular parenchyma and eventually linked with the barely altered portal tracts. Fifteen alcohol-fed baboons developed septums, with diffuse septal fibrosis in 5; 4 proceeded to septal cirrhosis and 1 each to micronodular and to mixed micromacronodular cirrhosis. Cirrhosis in the baboons thus develops without the conspicuous polymorphonuclear inflammation characteristic of human alcoholic hepatitis. These observations indicate a pathway to cirrhosis over creeping fibrosis that might play a role also in man, instead of (or supplementing) the one proceeding over alcoholic hepatitis.

  10. Non alcoholic steatohepatitis a precursor for hepatocellular carcinoma development

    PubMed Central

    Jiang, Chun-Meng; Pu, Chun-Wen; Hou, Ya-Hui; Chen, Zhe; Alanazy, Mohammed; Hebbard, Lionel

    2014-01-01

    Hepatocellular carcinoma (HCC) is increasing in prevalence and is one of the most common cancers in the world. Chief amongst the risks of attaining HCC are hepatitis B and C infection, aflatoxin B1 ingestion, alcoholism and obesity. The later has been shown to promote non alcoholic fatty liver disease, which can lead to the inflammatory form non alcoholic steatohepatitis (NASH). NASH is a complex metabolic disorder that can impact greatly on hepatic function. The mechanisms by which NASH promotes HCC are only beginning to be characterized. Here in this review, we give an overview of the recent novel mechanisms published that have been associated with NASH and subsequent HCC progression. We will focus our discussion on inflammation and gut derived inflammation and how they contribute to NASH driven HCC. PMID:25469014

  11. Hepatic encephalopathy: a review.

    PubMed

    Lizardi-Cervera, Javier; Almeda, Paloma; Guevara, Luis; Uribe, Misael

    2003-01-01

    Hepatic encephalopathy (HE) is a complication that presents in as many as 28% of patients with cirrhosis, and reported up to ten years after the diagnosis of cirrhosis. Commonly, it is observed in patients with severe hepatic failure and is characterized by neuropsychiatric manifestations that can range in severity from a mild alteration in mental state to a coma; additionally, some neuromuscular symptoms can be observed. This complication of either acute or chronic hepatic disease is the result of a diminished hepatic reservoir and inability to detoxify some toxins that originate in the bowel. Today, the role of astrocytes, specifically the Alzheimer type II cells, is known to be very important in the pathogenesis of the hepatic encephalopathy, and will be reviewed later. In conclusion, the objectives of this review are: To understand the pathogenesis of hepatic encephalopathy, To recognize the precipitating factors, as well as preventive measures for the development of the hepatic encephalopathy, To describe the new classification of hepatic encephalopathy and its clinical implications, To recognize the clinical manifestations and stages of the disease, To understand the main diagnostic tests used to detect the hepatic encephalopathy, To describe the main therapeutic treatments of hepatic encephalopathy. PMID:15115963

  12. An in-vitro comparative study for assessment of apical sealing ability of Epiphany/AH Plus sealer with Resilon/gutta-percha root canal filling materials

    PubMed Central

    Sultana, Meraj; Musani, Mohammad A.; Ahmed, Iffat M.

    2016-01-01

    Aims and Objectives: Endodontic treatment is directed to eliminate microbial challenges from the root canal system and to create a complete seal. The aim of this study was to assess the apical sealing ability of resin-based Epiphany-Resilon root canal filling system and to compare it with the sealing abilities of different combinations of AH Plus, gutta-percha, Epiphany, and Resilon. Materials and Methods: One hundred extracted human maxillary incisor roots were treated endodontically. The samples were divided into groups A, B, C, and D, with each group containing 25 samples. Group A: Canals obturated with gutta-percha and AH Plus sealer; Group B: Canals obturated with Resilon and Epiphany; Group C: Canals obturated with gutta-percha and Epiphany; Group D: Control group canals obturated with gutta-percha without a sealer. The sealing ability of each of the obturation techniques was tested using the dye penetration method followed by the clearing method using alcohol. Stereo microscope was used to measure the extent of dye penetration. Statistical data analysis was performed using analysis of variance and Tukey tests. Results: Microleakage was found in all the four groups. Apical extent of mean microleakage was maximum for gutta-percha, followed by Gutta-percha + AH-plus and Gutta-percha + Epiphany, and the least with Resilon + Epiphany. Statistically significant difference (P < 0.01) was seen in the apical leakage. Conclusion: All the samples tested showed microleakage. The “Epiphany soft resin endodontic obturation system” showed a superior result compared to other obturation materials. PMID:27583220

  13. Orlistat-induced fulminant hepatic failure.

    PubMed

    Sall, D; Wang, J; Rashkin, M; Welch, M; Droege, C; Schauer, D

    2014-12-01

    Orlistat was approved by the Food and Drug Administration in 1998 and has been shown to be superior to placebo in achieving weight loss. It is generally well tolerated. However, severe liver injury has been reported. We present a case of hepatic failure in a patient taking orlistat. A 54-year-old African-American woman with hypertension presented with hepatic failure. She had noticed increasing fatigue, jaundice and confusion. She used alcohol sparingly and denied tobacco or illicit drug use, but had been taking over-the-counter orlistat for the past two months. Physical examination revealed scleral icterus, jaundice, asterixis and slow speech. Laboratory testing showed markedly abnormal liver function tests with coagulopathy. Acute viral and autoimmune serologies were negative, as was toxicology screen. Liver biopsy showed necrotic hepatic parenchyma likely secondary to drug toxicity. Based upon her clinical presentation and time course, the pattern of liver injury seen on liver biopsy and lack of an alternative plausible explanation, her liver failure was most likely associated with orlistat use. She continued to deteriorate and ultimately underwent orthotopic liver transplantation. Fourteen cases of severe liver injury associated with orlistat use have been reported, four of which are detailed in the literature. This is the second published case of liver failure associated with over-the-counter orlistat usage. Clinicians should be aware of the growing number of cases associating liver injury and orlistat use and carefully monitor their patients on this medication for signs of hepatic dysfunction.

  14. Orlistat-induced fulminant hepatic failure.

    PubMed

    Sall, D; Wang, J; Rashkin, M; Welch, M; Droege, C; Schauer, D

    2014-12-01

    Orlistat was approved by the Food and Drug Administration in 1998 and has been shown to be superior to placebo in achieving weight loss. It is generally well tolerated. However, severe liver injury has been reported. We present a case of hepatic failure in a patient taking orlistat. A 54-year-old African-American woman with hypertension presented with hepatic failure. She had noticed increasing fatigue, jaundice and confusion. She used alcohol sparingly and denied tobacco or illicit drug use, but had been taking over-the-counter orlistat for the past two months. Physical examination revealed scleral icterus, jaundice, asterixis and slow speech. Laboratory testing showed markedly abnormal liver function tests with coagulopathy. Acute viral and autoimmune serologies were negative, as was toxicology screen. Liver biopsy showed necrotic hepatic parenchyma likely secondary to drug toxicity. Based upon her clinical presentation and time course, the pattern of liver injury seen on liver biopsy and lack of an alternative plausible explanation, her liver failure was most likely associated with orlistat use. She continued to deteriorate and ultimately underwent orthotopic liver transplantation. Fourteen cases of severe liver injury associated with orlistat use have been reported, four of which are detailed in the literature. This is the second published case of liver failure associated with over-the-counter orlistat usage. Clinicians should be aware of the growing number of cases associating liver injury and orlistat use and carefully monitor their patients on this medication for signs of hepatic dysfunction. PMID:25826164

  15. Nurses' Attitudes towards Alcoholics.

    ERIC Educational Resources Information Center

    Speer, Rita D.

    Nurses' attitudes toward the alcoholic can have a profound impact on the person suffering from alcoholism. These attitudes can affect the alcoholic's care and even whether the alcoholic chooses to recover. This study investigated attitudes of approximately 68 nurses employed in hospitals, 49 nurses in treatment facilities, 58 nursing students, and…

  16. Feature Hepatitis: Hepatitis Can Strike Anyone

    MedlinePlus

    ... please turn Javascript on. From Hollywood's "Walk of Stars" to Main Street, USA, people from all walks ... that includes many well-known names: Legendary television star Larry Hagman was diagnosed with advanced hepatitis C ...

  17. Internet Alcohol Marketing and Underage Alcohol Use

    PubMed Central

    McClure, Auden C.; Tanski, Susanne E.; Li, Zhigang; Jackson, Kristina; Morgenstern, Matthis; Li, Zhongze; Sargent, James D.

    2016-01-01

    BACKGROUND AND OBJECTIVE Internet alcohol marketing is not well studied despite its prevalence and potential accessibility and attractiveness to youth. The objective was to examine longitudinal associations between self-reported engagement with Internet alcohol marketing and alcohol use transitions in youth. METHODS A US sample of 2012 youths aged 15 to 20 was surveyed in 2011. An Internet alcohol marketing receptivity score was developed, based on number of positive responses to seeing alcohol advertising on the Internet, visiting alcohol brand Web sites, being an online alcohol brand fan, and cued recall of alcohol brand home page images. We assessed the association between baseline marketing receptivity and both ever drinking and binge drinking (≥6 drinks per occasion) at 1-year follow-up with multiple logistic regression, controlling for baseline drinking status, Internet use, sociodemographics, personality characteristics, and peer or parent drinking. RESULTS At baseline, ever-drinking and binge-drinking prevalence was 55% and 27%, respectively. Many (59%) reported seeing Internet alcohol advertising, but few reported going to an alcohol Web site (6%) or being an online fan (3%). Higher Internet use, sensation seeking, having family or peers who drank, and past alcohol use were associated with Internet alcohol marketing receptivity, and a score of 1 or 2 was independently associated with greater adjusted odds of initiating binge drinking (odds ratio 1.77; 95% confidence interval, 1.13–2.78 and odds ratio 2.15; 95% confidence interval, 1.06–4.37 respectively) but not with initiation of ever drinking. CONCLUSIONS Although high levels of engagement with Internet alcohol marketing were uncommon, most underage youths reported seeing it, and we found a prospective association between receptivity to this type of alcohol marketing and future problem drinking, making additional research and ongoing surveillance important. PMID:26738886

  18. Hepatitis E Outbreak on Cruise Ship

    PubMed Central

    Ijaz, Samreen; Kafatos, George; Booth, Linda; Thomas, H. Lucy; Walsh, Amanda; Ramsay, Mary; Morgan, Dilys

    2009-01-01

    In 2008, acute hepatitis E infection was confirmed in 4 passengers returning to the United Kingdom after a world cruise. Epidemiologic investigation showed that of 789 persons who provided blood samples, 195 (25%) were seropositive, 33 (4%) had immunoglobulin [Ig] M levels consistent with recent acute infection (11 of these persons were symptomatic), and 162 (21%) had IgG only, consistent with past infection. Passenger mean age was 68 years. Most (426/789, 54%) passengers were female, yet most with acute infection (25/33, 76%) were male. Sequencing of RNA from 3 case-patients identified hepatitis E virus genotype 3, closely homologous to genotype 3 viruses from Europe. Significant association with acute infection was found for being male, drinking alcohol, and consuming shellfish while on board (odds ratio 4.27, 95% confidence interval 1.23–26.94, p = 0.019). This was probably a common-source foodborne outbreak. PMID:19891860

  19. Alcohol and bone.

    PubMed

    Mikosch, Peter

    2014-01-01

    Alcohol is widely consumed across the world in different cultural and social settings. Types of alcohol consumption differ between (a) light, only occasional consumption, (b) heavy chronic alcohol consumption, and (c) binge drinking as seen as a new pattern of alcohol consumption among teenagers and young adults. Heavy alcohol consumption is detrimental to many organs and tissues, including bones. Osteoporosis is regularly mentioned as a secondary consequence of alcoholism, and chronic alcohol abuse is established as an independent risk factor for osteoporosis. The review will present the different mechanisms and effects of alcohol intake on bone mass, bone metabolism, and bone strength, including alcoholism-related "life-style factors" such as malnutrition, lack of exercise, and hormonal changes as additional causative factors, which also contribute to the development of osteoporosis due to alcohol abuse. PMID:24477631

  20. [Alcohol and arrhythmias].

    PubMed

    Pfeiffer, D; Jurisch, D; Neef, M; Hagendorff, A

    2016-09-01

    The effects of alcohol on induction of arrhythmias is dose-dependent, independent of preexisting cardiovascular diseases or heart failure and can affect otherwise healthy subjects. While the probability of atrial fibrillation increases with the alcohol dosage, events of sudden cardiac death are less frequent with low and moderate consumption but occur more often in heavy drinkers with alcoholic cardiomyopathy. Men are first affected at higher dosages of alcohol but women can suffer from arrhythmias at lower dosages. Thromboembolisms and ischemic stroke can occur less often at lower dosages of alcohol; however, hemorrhagic stroke and subarachnoid hemorrhage are increased with higher alcohol dosages. Recognizable protective mechanisms of alcohol with respect to cardiovascular diseases only occur with lower amounts of alcohol of less than 10 g per day. Underlying mechanisms explain these controversial effects. Specific therapeutic options for alcohol-related arrhythmias apart from abstinence from alcohol consumption are not known. PMID:27582366

  1. Combination hepatitis a-hepatitis B vaccine.

    PubMed

    Wagstaff, A J; Balfour, J A

    1997-09-01

    The adult formulation of this combination hepatitis A-hepatitis B vaccine contains 720 enzyme-linked immunosorbent assay units (EU) of formalin-inactivated hepatitis A virus strain HM175 and 20mug of recombinant DNA yeast-derived hepatitis B surface antigen adsorbed onto aluminium salts in 1ml for injection. The paediatric formulation contains half this dosage in 0.5ml for injection. The combination vaccine has been shown to be highly immunogenic in healthy young adults after the full dosage schedule of 3 doses at 0, 1 and 6 months. Trials in older adults and children indicate that immunogenicity is adequate in these groups also. The immunogenicity of the combination vaccine appears to be similar to that of hepatitis A vaccine and hepatitis B vaccine administered separately. Possible advantages for the combination vaccine recipient include fewer injections and lower costs. Local adverse reactions such as soreness at the injection site, redness and swelling occur often with the first dose of the series, but the incidence falls with subsequent doses. Local reactions are usually mild and transient, and reported systemic reactions (fatigue, headache) are thought not to have a causal link with the vaccine. PMID:18020513

  2. Biological role of Trichoderma harzianum-derived platelet-activating factor acetylhydrolase (PAF-AH) on stress response and antagonism.

    PubMed

    Yu, Chuanjin; Fan, Lili; Wu, Qiong; Fu, Kehe; Gao, Shigang; Wang, Meng; Gao, Jinxin; Li, Yaqian; Chen, Jie

    2014-01-01

    We investigated the properties of platelet-activating factor acetylhydrolase (PAF-AH) derived from Trichoderma harzianum. The enzyme, comprised of 572 amino acids, shares high homology with PAF-AH proteins from T. koningii and other microbial species. The optimum enzymatic activity of PAF-AH occurred at pH 6 in the absence of Ca2+ and it localized in the cytoplasm, and we observed the upregulation of PAF-AH expression in response to carbon starvation and strong heat shock. Furthermore, PAF-AH knockout transformant growth occurred more slowly than wild type cells and over-expression strains grown in SM medium at 37°C and 42°C. In addition, PAF-AH expression significantly increased under a series of maize root induction assay. Eicosanoic acid and ergosterol levels decreased in the PAF-AH knockouts compared to wild type cells, as revealed by GC/MS analysis. We also determined stress responses mediated by PAF-AH were related to proteins HEX1, Cu/Zn superoxide dismutase, and cytochrome c. Finally, PAF-AH exhibited antagonistic activity against Rhizoctonia solani in plate confrontation assays. Our results indicate PAF-AH may play an important role in T. harzianum stress response and antagonism under diverse environmental conditions.

  3. Emergence in China of human disease due to avian influenza A(H10N8)--cause for concern?

    PubMed

    To, Kelvin K W; Tsang, Alan K L; Chan, Jasper F W; Cheng, Vincent C C; Chen, Honglin; Yuen, Kwok-Yung

    2014-03-01

    In December 2013, China reported the first human case of avian influenza A(H10N8). A 73-year-old female with chronic diseases who had visited a live poultry market succumbed with community-acquired pneumonia. While human infections with avian influenza viruses are usually associated with subtypes prevalent in poultries, A(H10N8) isolates were mostly found in migratory birds and only recently in poultries. Although not possible to predict whether this single intrusion by A(H10N8) is an accident or the start of another epidemic like the preceding A(H7N9) and A(H5N1), several features suggest that A(H10N8) is a potential threat to humans. Recombinant H10 could attach to human respiratory epithelium, and A(H10N4) virus could cause severe infections in minks and chickens. A(H10N8) viruses contain genetic markers for mammalian adaptation and virulence in the haemagglutinin (A135T, S138A[H3 numbering]), M1(N30D, T215A), NS1(P42S) and PB2(E627K) protein. Studies on this human A(H10N8) isolate will reveal its adaptability to humans. Clinicians should alert the laboratory to test for A(H5,6,7,9,10) viruses in patients with epidemiological exposure in endemic geographical areas especially when human influenza A(H1,3) and B are negative. Vigilant virological and serological surveillance for A(H10N8) in human, poultry and wild bird is important for following the trajectory of this emerging influenza virus.

  4. Alcohol fuels

    SciTech Connect

    Not Available

    1990-07-01

    Ethanol is an alcohol made from grain that can be blended with gasoline to extend petroleum supplies and to increase gasoline octane levels. Congressional proposals to encourage greater use of alternative fuels could increase the demand for ethanol. This report evaluates the growth potential of the ethanol industry to meet future demand increases and the impacts increased production would have on American agriculture and the federal budget. It is found that ethanol production could double or triple in the next eight years, and that American farmers could provide the corn for this production increase. While corn growers would benefit, other agricultural segments would not; soybean producers, for example could suffer for increased corn oil production (an ethanol byproduct) and cattle ranchers would be faced with higher feed costs because of higher corn prices. Poultry farmers might benefit from lower priced feed. Overall, net farm cash income should increase, and consumers would see slightly higher food prices. Federal budget impacts would include a reduction in federal farm program outlays by an annual average of between $930 million (for double current production of ethanol) to $1.421 billion (for triple production) during the eight-year growth period. However, due to an partial tax exemption for ethanol blended fuels, federal fuel tax revenues could decrease by between $442 million and $813 million.

  5. Hepatic apoptosis can modulate liver fibrosis through TIMP1 pathway.

    PubMed

    Wang, Kewei; Lin, Bingliang; Brems, John J; Gamelli, Richard L

    2013-05-01

    Apoptotic injury participates in hepatic fibrosis, but the molecular mechanisms are not well understood. The present study aimed to investigate the role of inducible TIMP1 in the pathogenesis of hepatic apoptosis-fibrosis. Apoptosis was induced with GCDC, LPS, and alcohol in precision-cut liver slices or bile duct ligation (BDL) in rats, as reflected by caspase-3 activity, TUNEL assay, and apoptosis-related gene profiles. The hepatic fibrosis was detected with Picrosirius staining, hydroxyproline determination, and expression profiling of fibrosis-related genes. Levels of TIMP1 were upregulated by the hepatic apoptosis, but downregulated by caspase inhibitor. The inducible TIMP1 was apoptosis-dependent. Once TIMP1 was inhibited with treatment of TIMP1-siRNA, the fibrotic response was reduced as demonstrated by hydroxyproline assay. In addition, the expression of fibrosis-related genes aSMA, CTGF, and TGFb2r were down-regulated subsequent to the treatment of TIMP1-siRNA. TIMP1 could mediate the expression of fibrosis-related genes. TIMP1 was transcriptionally regulated by nuclear factor c-Jun as demonstrated by EMSA and ChIP assay. The treatment of c-Jun siRNA could significantly decrease the expression of TIMP1 induced by alcohol, GCDC, or LPS treatment. Hepatic apoptosis induces the expression of TIMP1. Inducible TIMP1 can modulate the expression of fibrosis-related genes in liver. TIMP1 pathway is a potential target for therapeutic intervention of fibrotic liver diseases.

  6. Liver fibrosis markers in alcoholic liver disease.

    PubMed

    Chrostek, Lech; Panasiuk, Anatol

    2014-07-01

    Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease (ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have been used to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APRI indexes, FIB4, an algorithm combining Prothrombin index (PI), α-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients. PMID:25009372

  7. Hepatitis C: Information on Testing and Diagnosis

    MedlinePlus

    HEPATITIS C Information on Testing & Diagnosis What is Hepatitis C? Hepatitis C is a serious liver disease that results from infection with the Hepatitis C virus. Hepatitis C has been called a silent ...

  8. Summary of AH-1G flight vibration data for validation of coupled rotor-fuselage analyses

    NASA Technical Reports Server (NTRS)

    Dompka, R. V.; Cronkhite, J. D.

    1986-01-01

    Under a NASA research program designated DAMVIBS (Design Analysis Methods for VIBrationS), four U. S. helicopter industry participants (Bell Helicopter, Boeing Vertol, McDonnell Douglas Helicopter, and Sikorsky Aircraft) are to apply existing analytical methods for calculating coupled rotor-fuselage vibrations of the AH-1G helicopter for correlation with flight test data from an AH-1G Operational Load Survey (OLS) test program. Bell Helicopter, as the manufacturer of the AH-1G, was asked to provide pertinent rotor data and to collect the OLS flight vibration data needed to perform the correlations. The analytical representation of the fuselage structure is based on a NASTRAN finite element model (FEM) developed by Bell which has been extensively documented and correlated with ground vibration tests.The AH-1G FEM was provided to each of the participants for use in their coupled rotor-fuselage analyses. This report describes the AH-1G OLS flight test program and provides the flight conditions and measured vibration data to be used by each participant in their correlation effort. In addition, the mechanical, structural, inertial and aerodynamic data for the AH-1G two-bladed teetering main rotor system are presented. Furthermore, modifications to the NASTRAN FEM of the fuselage structure that are necessary to make it compatible with the OLS test article are described. The AH-1G OLS flight test data was found to be well documented and provide a sound basis for evaluating currently existing analysis methods used for calculation of coupled rotor-fuselage vibrations.

  9. Phylodynamics of influenza A(H3N2) in South America, 1999-2012.

    PubMed

    Born, Priscila Silva; Siqueira, Marilda Mendonça; Faria, Nuno Rodrigues; Resende, Paola Cristina; Motta, Fernando Couto; Bello, Gonzalo

    2016-09-01

    The limited influenza A(H3N2) genetic data available from the Southern Hemisphere (particularly from Africa and Latin America), constrains the accurate reconstruction of viral dissemination dynamics within those regions. Our objective was to describe the spatial dissemination dynamics of influenza A(H3N2) within South America. A total of 469 sequences of the HA1 portion of the hemagglutinin gene (HA) from influenza A(H3N2) viruses sampled in temperate and tropical South American countries between 1999 and 2012 were combined with available contemporary sequences from Australia, Hong Kong, United Kingdom and the United States. Phylogenetic analyses revealed that influenza A(H3N2) sequences from South America were highly intermixed with sequences from other geographical regions, although a clear geographic virus population structure was detected globally. We identified 14 clades mostly (≥80%) composed of influenza sequences from South American countries. Bayesian phylogeographic analyses of those clades support a significant role of both temperate and tropical regions in the introduction and dissemination of new influenza A(H3N2) strains within South America and identify an intensive bidirectional viral exchange between different geographical areas. These findings indicate that seasonal influenza A(H3N2) epidemics in South America are seeded by both the continuous importation of viral variants from other geographic regions and the short-term persistence of local lineages. This study also supports a complex metapopulation model of influenza A(H3N2) dissemination in South America, with no preferential direction in viral movement between temperate and tropical regions. PMID:27275847

  10. Clinical effectiveness of KSS formula, a traditional folk remedy for alcohol hangover symptoms.

    PubMed

    Takahashi, Mizuho; Li, Wei; Koike, Kazuo; Sadamoto, Kiyomi

    2010-10-01

    A formula (KSS formula) containing the pith of Citrus tangerine Hort. et Tanaka (Kitsuraku), the rhizome of Zingiber officinale (Shokyo), and brown sugar has been traditionally used in China for the treatment of discomfort and cold sensation in the abdomen after ingestion of large amounts of alcohol. We evaluated the clinical effectiveness of this formula on signs and symptoms of alcohol hangover (AH). Of the twenty-two symptoms listed, significant decreases in severity scores were shown in nausea, vomiting, and diarrhea when the formula was administered in scheduled prophylactic doses. The score in overall well-being, ranging from 0 to 100 (worst possible condition), was 68.9 +/- 16.5 (mean +/- SD) in the control group and it decreased to 46.9 +/- 27.3 and to 44.4 +/- 26.4 in the two groups that included a dosing point prior to alcohol ingestion. Regardless of dosing schedules, KSS formula did not alter the time required for complete recovery from AH symptoms. These findings suggest the possibility that KSS formula may become a candidate for AH remedy when administered prophylactically.

  11. Genome-Wide Analysis of Evolutionary Markers of Human Influenza A(H1N1)pdm09 and A(H3N2) Viruses May Guide Selection of Vaccine Strain Candidates

    PubMed Central

    Belanov, Sergei S.; Bychkov, Dmitrii; Benner, Christian; Ripatti, Samuli; Ojala, Teija; Kankainen, Matti; Kai Lee, Hong; Wei-Tze Tang, Julian; Kainov, Denis E.

    2015-01-01

    Here we analyzed whole-genome sequences of 3,969 influenza A(H1N1)pdm09 and 4,774 A(H3N2) strains that circulated during 2009–2015 in the world. The analysis revealed changes at 481 and 533 amino acid sites in proteins of influenza A(H1N1)pdm09 and A(H3N2) strains, respectively. Many of these changes were introduced as a result of random drift. However, there were 61 and 68 changes that were present in relatively large number of A(H1N1)pdm09 and A(H3N2) strains, respectively, that circulated during relatively long time. We named these amino acid substitutions evolutionary markers, as they seemed to contain valuable information regarding the viral evolution. Interestingly, influenza A(H1N1)pdm09 and A(H3N2) viruses acquired non-overlapping sets of evolutionary markers. We next analyzed these characteristic markers in vaccine strains recommended by the World Health Organization for the past five years. Our analysis revealed that vaccine strains carried only few evolutionary markers at antigenic sites of viral hemagglutinin (HA) and neuraminidase (NA). The absence of these markers at antigenic sites could affect the recognition of HA and NA by human antibodies generated in response to vaccinations. This could, in part, explain moderate efficacy of influenza vaccines during 2009–2014. Finally, we identified influenza A(H1N1)pdm09 and A(H3N2) strains, which contain all the evolutionary markers of influenza A strains circulated in 2015, and which could be used as vaccine candidates for the 2015/2016 season. Thus, genome-wide analysis of evolutionary markers of influenza A(H1N1)pdm09 and A(H3N2) viruses may guide selection of vaccine strain candidates. PMID:26615216

  12. Genome-Wide Analysis of Evolutionary Markers of Human Influenza A(H1N1)pdm09 and A(H3N2) Viruses May Guide Selection of Vaccine Strain Candidates.

    PubMed

    Belanov, Sergei S; Bychkov, Dmitrii; Benner, Christian; Ripatti, Samuli; Ojala, Teija; Kankainen, Matti; Kai Lee, Hong; Wei-Tze Tang, Julian; Kainov, Denis E

    2015-11-27

    Here we analyzed whole-genome sequences of 3,969 influenza A(H1N1)pdm09 and 4,774 A(H3N2) strains that circulated during 2009-2015 in the world. The analysis revealed changes at 481 and 533 amino acid sites in proteins of influenza A(H1N1)pdm09 and A(H3N2) strains, respectively. Many of these changes were introduced as a result of random drift. However, there were 61 and 68 changes that were present in relatively large number of A(H1N1)pdm09 and A(H3N2) strains, respectively, that circulated during relatively long time. We named these amino acid substitutions evolutionary markers, as they seemed to contain valuable information regarding the viral evolution. Interestingly, influenza A(H1N1)pdm09 and A(H3N2) viruses acquired non-overlapping sets of evolutionary markers. We next analyzed these characteristic markers in vaccine strains recommended by the World Health Organization for the past five years. Our analysis revealed that vaccine strains carried only few evolutionary markers at antigenic sites of viral hemagglutinin (HA) and neuraminidase (NA). The absence of these markers at antigenic sites could affect the recognition of HA and NA by human antibodies generated in response to vaccinations. This could, in part, explain moderate efficacy of influenza vaccines during 2009-2014. Finally, we identified influenza A(H1N1)pdm09 and A(H3N2) strains, which contain all the evolutionary markers of influenza A strains circulated in 2015, and which could be used as vaccine candidates for the 2015/2016 season. Thus, genome-wide analysis of evolutionary markers of influenza A(H1N1)pdm09 and A(H3N2) viruses may guide selection of vaccine strain candidates.

  13. Aetiology and pathogenesis of alcoholic liver disease.

    PubMed

    Lieber, C S

    1993-09-01

    Until the 1960s, liver disease of the alcoholic patient was attributed exclusively to dietary deficiencies. Since then, however, our understanding of the impact of alcoholism on nutritional status has undergone a progressive evolution. Alcohol, because of its high energy content, was at first perceived to act exclusively as 'empty calories' displacing other nutrients in the diet, and causing primary malnutrition through decreased intake of essential nutrients. With improvement in the overall nutrition of the population, the role of primary malnutrition waned and secondary malnutrition was emphasized as a result of a better understanding of maldigestion and malabsorption caused by chronic alcohol consumption and various diseases associated with chronic alcoholism. At the same time, the concept of the direct toxicity of alcohol came to the forefront as an explanation for the widespread cellular injury. Some of the hepatotoxicity was found to result from the metabolic disturbances associated with the oxidation of ethanol via the liver alcohol dehydrogenase (ADH) pathway and the redox changes produced by the generated NADH, which in turn affects the metabolism of lipids, carbohydrates, proteins and purines. Exaggeration of the redox change by the relative hypoxia which prevails physiologically in the perivenular zone contributes to the exacerbation of the ethanol-induced lesions in zone 3. In addition to ADH, ethanol can be oxidized by liver microsomes: studies over the last twenty years have culminated in the molecular elucidation of the ethanol-inducible cytochrome P450IIE1 (CYP2E1) which contributes not only to ethanol metabolism and tolerance, but also to the selective hepatic perivenular toxicity of various xenobiotics. Their activation by CYP2E1 now provides an understanding for the increased susceptibility of the heavy drinker to the toxicity of industrial solvents, anaesthetic agents, commonly prescribed drugs, 'over the counter' analgesics, chemical

  14. Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes.

    PubMed

    Tolstrup, Janne Schurmann; Nordestgaard, Børge Grønne; Rasmussen, Søren; Tybjaerg-Hansen, Anne; Grønbaek, Morten

    2008-06-01

    Alcohol drinking habits and alcoholism are partly genetically determined. Alcohol is degraded primarily by alcohol dehydrogenase (ADH) wherein genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. It is biologically plausible that these variations may be associated with alcohol drinking habits and alcoholism. By genotyping 9080 white men and women from the general population, we found that men and women with ADH1B slow vs fast alcohol degradation drank more alcohol and had a higher risk of everyday drinking, heavy drinking, excessive drinking and of alcoholism. For example, the weekly alcohol intake was 9.8 drinks (95% confidence interval (CI): 9.1-11) among men with the ADH1B.1/1 genotype compared to 7.5 drinks (95% CI: 6.4-8.7) among men with the ADH1B.1/2 genotype, and the odds ratio (OR) for heavy drinking was 3.1 (95% CI: 1.7-5.7) among men with the ADH1B.1/1 genotype compared to men with the ADH1B.1/2 genotype. Furthermore, individuals with ADH1C slow vs fast alcohol degradation had a higher risk of heavy and excessive drinking. For example, the OR for heavy drinking was 1.4 (95% CI: 1.1-1.8) among men with the ADH1C.1/2 genotype and 1.4 (95% CI: 1.0-1.9) among men with the ADH1B.2/2 genotype, compared with men with the ADH1C.1/1 genotype. Results for ADH1B and ADH1C genotypes among men and women were similar. Finally, because slow ADH1B alcohol degradation is found in more than 90% of the white population compared to less than 10% of East Asians, the population attributable risk of heavy drinking and alcoholism by ADH1B.1/1 genotype was 67 and 62% among the white population compared with 9 and 24% among the East Asian population.

  15. Perillyl Alcohol (Monoterpene Alcohol), Limonene.

    PubMed

    Shojaei, Shahla; Kiumarsi, Amir; Moghadam, Adel Rezaei; Alizadeh, Javad; Marzban, Hassan; Ghavami, Saeid

    2014-01-01

    Natural products have a long history of use in traditional medicines and their activities against different diseases have been the focus of many basic and clinical researches in past few decades. The essential oils, volatile liquid containing aroma compound from plants, are known as active ingredients in the herbal medicine. Perillyl alcohol (POH) is usually available through dietary sources and is being explored for its cancer chemoprevention, tumor growth suppression, and regression. Citrus peels are the waste product of juice manufacturing industries and have been considered as a critical problem for environmental green ecology policies for years. One of the most well-known approaches to overcome this problem is transformation of these monoterpene by the use of specific strains of bacteria or yeasts. Limonene (1-methyl-4-isopropyl-cyclohexene) is a monoterpene, as other monoterpenes consists of two isoprene units, that comprises more than 90% of citrus essential oil and it exists in many fruits and vegetables. Although, the anticancer activity of d-limonene has identified nearly two decades ago, it has recently attracted much more attention in translational medicine. In this chapter, we will overview the anticancer effects of POH and d-limonene. Later, we will address the pharmacokinetics of these compounds, highlight the signaling pathways which are targeted by these proteins, review the clinical trials which have been done for these compounds in different cancer models, and finally discuss the future directions of the research in this field that might be more applicable in future cancer therapy strategies.

  16. Perillyl Alcohol (Monoterpene Alcohol), Limonene.

    PubMed

    Shojaei, Shahla; Kiumarsi, Amir; Moghadam, Adel Rezaei; Alizadeh, Javad; Marzban, Hassan; Ghavami, Saeid

    2014-01-01

    Natural products have a long history of use in traditional medicines and their activities against different diseases have been the focus of many basic and clinical researches in past few decades. The essential oils, volatile liquid containing aroma compound from plants, are known as active ingredients in the herbal medicine. Perillyl alcohol (POH) is usually available through dietary sources and is being explored for its cancer chemoprevention, tumor growth suppression, and regression. Citrus peels are the waste product of juice manufacturing industries and have been considered as a critical problem for environmental green ecology policies for years. One of the most well-known approaches to overcome this problem is transformation of these monoterpene by the use of specific strains of bacteria or yeasts. Limonene (1-methyl-4-isopropyl-cyclohexene) is a monoterpene, as other monoterpenes consists of two isoprene units, that comprises more than 90% of citrus essential oil and it exists in many fruits and vegetables. Although, the anticancer activity of d-limonene has identified nearly two decades ago, it has recently attracted much more attention in translational medicine. In this chapter, we will overview the anticancer effects of POH and d-limonene. Later, we will address the pharmacokinetics of these compounds, highlight the signaling pathways which are targeted by these proteins, review the clinical trials which have been done for these compounds in different cancer models, and finally discuss the future directions of the research in this field that might be more applicable in future cancer therapy strategies. PMID:27102697

  17. International Laboratory Comparison of Influenza Microneutralization Assays for A(H1N1)pdm09, A(H3N2), and A(H5N1) Influenza Viruses by CONSISE.

    PubMed

    Laurie, Karen L; Engelhardt, Othmar G; Wood, John; Heath, Alan; Katz, Jacqueline M; Peiris, Malik; Hoschler, Katja; Hungnes, Olav; Zhang, Wenqing; Van Kerkhove, Maria D

    2015-08-01

    The microneutralization assay is commonly used to detect antibodies to influenza virus, and multiple protocols are used worldwide. These protocols differ in the incubation time of the assay as well as in the order of specific steps, and even within protocols there are often further adjustments in individual laboratories. The impact these protocol variations have on influenza serology data is unclear. Thus, a laboratory comparison of the 2-day enzyme-linked immunosorbent assay (ELISA) and 3-day hemagglutination (HA) microneutralization (MN) protocols, using A(H1N1)pdm09, A(H3N2), and A(H5N1) viruses, was performed by the CONSISE Laboratory Working Group. Individual laboratories performed both assay protocols, on multiple occasions, using different serum panels. Thirteen laboratories from around the world participated. Within each laboratory, serum sample titers for the different assay protocols were compared between assays to determine the sensitivity of each assay and were compared between replicates to assess the reproducibility of each protocol for each laboratory. There was good correlation of the results obtained using the two assay protocols in most laboratories, indicating that these assays may be interchangeable for detecting antibodies to the influenza A viruses included in this study. Importantly, participating laboratories have aligned their methodologies to the CONSISE consensus 2-day ELISA and 3-day HA MN assay protocols to enable better correlation of these assays in the future.

  18. Inflammatory status in human hepatic cirrhosis

    PubMed Central

    Martínez-Esparza, María; Tristán-Manzano, María; Ruiz-Alcaraz, Antonio J; García-Peñarrubia, Pilar

    2015-01-01

    This review focuses on new findings about the inflammatory status involved in the development of human liver cirrhosis induced by the two main causes, hepatitis C virus (HCV) infection and chronic alcohol abuse, avoiding results obtained from animal models. When liver is faced to a persistent and/or intense local damage the maintained inflammatory response gives rise to a progressive replacement of normal hepatic tissue by non-functional fibrotic scar. The imbalance between tissue regeneration and fibrosis will determine the outcome toward health recovery or hepatic cirrhosis. In all cases progression toward liver cirrhosis is caused by a dysregulation of mechanisms that govern the balance between activation/homeostasis of the immune system. Detecting differences between the inflammatory status in HCV-induced vs alcohol-induced cirrhosis could be useful to identify specific targets for preventive and therapeutic intervention in each case. Thus, although survival of patients with alcoholic cirrhosis seems to be similar to that of patients with HCV-related cirrhosis (HCV-C), there are important differences in the altered cellular and molecular mechanisms implicated in the progression toward human liver cirrhosis. The predominant features of HCV-C are more related with those that allow viral evasion of the immune defenses, especially although not exclusively, inhibition of interferons secretion, natural killer cells activation and T cell-mediated cytotoxicity. On the contrary, the inflammatory status of alcohol-induced cirrhosis is determined by the combined effect of direct hepatotoxicity of ethanol metabolites and increases of the intestinal permeability, allowing bacteria and bacterial products translocation, into the portal circulation, mesenteric lymph nodes and peritoneal cavity. This phenomenon generates a stronger pro-inflammatory response compared with HCV-related cirrhosis. Hence, therapeutic intervention in HCV-related cirrhosis must be mainly focused to

  19. Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research

    PubMed Central

    Willebrords, Joost; Pereira, Isabel Veloso Alves; Maes, Michaël; Yanguas, Sara Crespo; Colle, Isabelle; Van Den Bossche, Bert; Da silva, Tereza Cristina; Oliveira, Cláudia P; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Cogliati, Bruno; Vinken, Mathieu

    2015-01-01

    Non-alcoholic fatty liver disease encompasses a spectrum of liver diseases, including simple steatosis, steatohepatitis, liver fibrosis and cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is currently the most dominant chronic liver disease in Western countries due to the fact that hepatic steatosis is associated with insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome and drug-induced injury. A variety of chemicals, mainly drugs, and diets is known to cause hepatic steatosis in humans and rodents. Experimental non-alcoholic fatty liver disease models rely on the application of a diet or the administration of drugs to laboratory animals or the exposure of hepatic cell lines to these drugs. More recently, genetically modified rodents or zebrafish have been introduced as non-alcoholic fatty liver disease models. Considerable interest now lies in the discovery and development of novel non-invasive biomarkers of non-alcoholic fatty liver disease, with specific focus on hepatic steatosis. Experimental diagnostic biomarkers of non-alcoholic fatty liver disease, such as (epi)genetic parameters and ‘-omics’-based read-outs are still in their infancy, but show great promise. . In this paper, the array of tools and models for the study of liver steatosis is discussed. Furthermore, the current state-of-art regarding experimental biomarkers such as epigenetic, genetic, transcriptomic, proteomic and metabonomic biomarkers will be reviewed. PMID:26073454

  20. Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets

    PubMed Central

    Herfst, Sander; Schrauwen, Eefje J. A.; Linster, Martin; Chutinimitkul, Salin; de Wit, Emmie; Munster, Vincent J.; Sorrell, Erin M.; Bestebroer, Theo M.; Burke, David F.; Smith, Derek J.; Rimmelzwaan, Guus F.; Osterhaus, Albert D. M. E.; Fouchier, Ron A. M.

    2016-01-01

    Highly pathogenic avian influenza A/H5N1 virus can cause morbidity and mortality in humans but thus far has not acquired the ability to be transmitted by aerosol or respiratory droplet (“airborne transmission”) between humans. To address the concern that the virus could acquire this ability under natural conditions, we genetically modified A/H5N1 virus by site-directed mutagenesis and subsequent serial passage in ferrets. The genetically modified A/H5N1 virus acquired mutations during passage in ferrets, ultimately becoming airborne transmissible in ferrets. None of the recipient ferrets died after airborne infection with the mutant A/H5N1 viruses. Four amino acid substitutions in the host receptor-binding protein hemagglutinin, and one in the polymerase complex protein basic polymerase 2, were consistently present in airborne-transmitted viruses. The transmissible viruses were sensitive to the antiviral drug oseltamivir and reacted well with antisera raised against H5 influenza vaccine strains. Thus, avian A/H5N1 influenza viruses can acquire the capacity for airborne transmission between mammals without recombination in an intermediate host and therefore constitute a risk for human pandemic influenza. PMID:22723413

  1. Long-Term Cytotoxicity, pH and Dissolution Rate of AH Plus and MTA Fillapex.

    PubMed

    Silva, Emmanuel João Nogueira Leal da; Accorsi-Mendonça, Thais; Pedrosa, Ana Carolina; Granjeiro, José Mauro; Zaia, Alexandre A

    2016-01-01

    The aim of the present study was to verify the long-term cytotoxic effects of the MTA Fillapex and to compare them with AH Plus. Dissolution rate and pH were also evaluated. Human osteoblast cells were incubated with elutes of fresh specimens from AH Plus and MTA Fillapex, and with elutes of the same specimens for 4 successive weeks. Elute's pH was evaluated at each time point. A multiparametric cell viability assay was performed. For dissolution rate, ISO methodology was used. The results were analyzed by one-way analysis of variance, complemented with the Tukey post-test (p<0.05). No significant difference was found among the materials when fresh mixed (p>0.05). After 1 week, AH Plus became non-cytotoxic on all three evaluated parameters. Conversely, MTA Fillapex remained severely and mildly cytotoxic over the entire experimental period (p<0.05). The dissolution rate of AH Plus was significantly lower than MTA Fillapex at all time points (p>0.05). The pH of AH Plus was significantly lower than MTA Fillapex at the second and third week (p<0.05). In the other tested time points no statistical difference was observed. In conclusion, MTA Fillapex remained cytotoxic after 4 weeks and its cytotoxicity may be related to the high dissolution rate of this material. PMID:27652704

  2. Effects of scorched food leachates with or without activated charcoal pretreatment on AhR activation in cultured cells.

    PubMed

    Takahashi, Satoshi; Morita, Koji; Kinoshita, Makoto; Fujimori, Shin; Ishikawa, Toshio

    2015-12-01

    Aryl hydrocarbon receptor (AhR) is a transcription factor activated by xenobiotics, including dioxins and polycyclic aromatic hydrocarbons (PAHs). Although AhR is also activated by some dietary constituents, it has not been completely clarified in what circumstances AhR ligands are ingested in our daily life. Because PAHs are formed by the incomplete combustion of organic materials, we hypothesized that scorched foods might contain and leach out AhR ligands sufficient to stimulate AhR in vitro. To test this hypothesis, scorched foods (bread, cheese, etc.) were mixed vigorously with water, and the supernatants were retrieved as samples. The samples were added to HepG2 cells stably expressing an AhR-responsive reporter gene. Also, expression of CYP1A1, an endogenous AhR-responsive gene, was analyzed by RT-PCR in different cell lines treated with the samples. We further tested whether pretreatment of the samples with activated charcoal would alter their AhR-stimulating activity. All the supernatant samples tested induced AhR-dependent reporter gene activity and CYP1A1 mRNA expression. In some samples, these inductions were inhibited by pretreatment with activated charcoal. Our findings indicate that scorched food leachates stimulate AhR in cultured cells and that activated charcoal adsorbs the AhR-stimulating substances in some leachates. Thus, people who habitually eat scorched foods are exposed to AhR ligands on a regular basis. Further studies are needed to elucidate whether burnt foods actually exert biological effects on our health.

  3. Effects of scorched food leachates with or without activated charcoal pretreatment on AhR activation in cultured cells.

    PubMed

    Takahashi, Satoshi; Morita, Koji; Kinoshita, Makoto; Fujimori, Shin; Ishikawa, Toshio

    2015-12-01

    Aryl hydrocarbon receptor (AhR) is a transcription factor activated by xenobiotics, including dioxins and polycyclic aromatic hydrocarbons (PAHs). Although AhR is also activated by some dietary constituents, it has not been completely clarified in what circumstances AhR ligands are ingested in our daily life. Because PAHs are formed by the incomplete combustion of organic materials, we hypothesized that scorched foods might contain and leach out AhR ligands sufficient to stimulate AhR in vitro. To test this hypothesis, scorched foods (bread, cheese, etc.) were mixed vigorously with water, and the supernatants were retrieved as samples. The samples were added to HepG2 cells stably expressing an AhR-responsive reporter gene. Also, expression of CYP1A1, an endogenous AhR-responsive gene, was analyzed by RT-PCR in different cell lines treated with the samples. We further tested whether pretreatment of the samples with activated charcoal would alter their AhR-stimulating activity. All the supernatant samples tested induced AhR-dependent reporter gene activity and CYP1A1 mRNA expression. In some samples, these inductions were inhibited by pretreatment with activated charcoal. Our findings indicate that scorched food leachates stimulate AhR in cultured cells and that activated charcoal adsorbs the AhR-stimulating substances in some leachates. Thus, people who habitually eat scorched foods are exposed to AhR ligands on a regular basis. Further studies are needed to elucidate whether burnt foods actually exert biological effects on our health. PMID:26558458

  4. A human intervention study with foods containing natural Ah-receptor agonists does not significantly show AhR-mediated effects as measured in blood cells and urine.

    PubMed

    de Waard, Pim W J; Peijnenburg, Ad A C M; Baykus, Hakan; Aarts, Jac M M J G; Hoogenboom, Ron L A P; van Schooten, Frederik J; de Kok, Theo M C M

    2008-10-22

    Binding and activation of the aryl hydrocarbon receptor (AhR) is thought to be an essential step in the toxicity of the environmental pollutants dioxins and dioxin-like PCBs. However, also a number of natural compounds, referred to as NAhRAs (natural Ah-receptor agonists), which are present in, for example, fruits and vegetables, can bind and activate this receptor. To study their potential effects in humans, we first investigated the effect of the prototypical AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gene expression in ex vivo exposed freshly isolated human lymphocytes, and compared the resulting gene expression profile with those caused by the well-known NAhRA indolo[3,2-b]carbazole (ICZ), originating from cruciferous vegetables, and by a hexane extract of NAhRA-containing grapefruit juice (GJE). Only ICZ induced a gene expression profile similar to TCDD in the lymphocytes, and both significantly up-regulated CYP1B1 and TIPARP (TCDD-inducible poly (ADP-ribose) polymerase) mRNA. Next, we performed a human intervention study with NAhRA-containing cruciferous vegetables and grapefruit juice. The expression of the prototypical AhR-responsive genes CYP1A1, CYP1B1 and NQO1 in whole blood cells and in freshly isolated lymphocytes was not significantly affected. Also enzyme activities of CYP1A2, CYP2A6, N-acetyltransferase 2 (NAT2) and xanthine oxidase (XO), as judged by caffeine metabolites in urine, were unaffected, except for a small down-regulation of NAT2 activity by grapefruit juice. Examination of blood plasma with DR CALUX showed a 12% increased AhR agonist activity 3 and 24 h after consumption of cruciferous vegetables, but did not show a significant effect of grapefruit juice consumption. We conclude that intake of NAhRAs from food may result in minor AhR-related effects measurable in human blood and urine. PMID:18762178

  5. [Effect of painting work on alcoholic liver dysfunction].

    PubMed

    Goji, Junko; Tsuchiya, Goro; Fujita, Daisuke; Koizumi, Naoko

    2003-11-01

    The effect of painting on alcoholic liver dysfunction was investigated. The subjects were male workers engaged in small-scale enterprises under contract to with heavy industries. Painting involved metal cleaning and painting, and the air concentrations of organic solvents were frequently high. The study population consisted of 1,157 male workers over 40 yr of age. Of them, 85 were painters engaged for a mean duration of 20.9 +/- 9.8 yr. There was no significant difference in GOT and GPT between painters who did not drink and non-painters who did not drink, but GOT and GPT were significantly higher in painters drinking several days a week than in non-painters. A past history of hepatitis affected GOT, GPT and gamma-GTP. Painting, daily alcohol consumption, drinking frequency and body mass index affected gamma-GTP. A questionnaire survey of hepatitis was also conducted in 206 male workers (age range 18-67 yr). Of them, 134 were painters (mean duration of painting, 16.8 +/- 10.4 yr). This questionnaire survey showed that 13 painters (9.6% of the painters) and two non-painters (2.6% of the non-painters) had a history of hepatitis. Of the 13 painters, five painters had a history of hepatitis C and four had a history of alcoholic hepatitis. All of these 13 painters had the habit of drinking. This study indicated that painting had little effect on the liver function in painters not drinking, but increased alcoholic liver dysfunction in painters with the drinking habit. PMID:14696391

  6. Neurologic effects of alcoholism.

    PubMed Central

    Diamond, I; Messing, R O

    1994-01-01

    Alcoholism, a worldwide disorder, is the cause of a variety of neurologic disorders. In this article we discuss the cellular pathophysiology of ethanol addition and abuse as well as evidence supporting and refuting the role of inheritance in alcoholism. A genetic marker for alcoholism has not been identified, but neurophysiologic studies may be promising. Some neurologic disorders related to longterm alcoholism are due predominantly to inadequate nutrition (the thiamine deficiency that causes Wernicke's encephalopathy), but others appear to involve the neurotoxicity of ethanol on brain (alcohol withdrawal syndrome and dementia) and peripheral nerves (alcoholic neuropathy and myopathy). Images PMID:7975567

  7. Pregnancy outcomes associated with viral hepatitis.

    PubMed

    Reddick, K L B; Jhaveri, R; Gandhi, M; James, A H; Swamy, G K

    2011-07-01

    The aim of this study was to examine the contribution of hepatitis B virus (HBV) and hepatitis C virus (HCV) to pregnancy-related complications including gestational diabetes mellitus (GDM), preterm birth (PTB), intrauterine growth restriction (IUGR), pre-eclampsia, antepartum haemorrhage and cholestasis. The Nationwide Inpatient Sample was queried for all pregnancy-related discharges, pregnancy complications and viral hepatitis from 1995 to 2005. Logistic regression was used to examine the association between HBV, HCV, HBV + HCV and pregnancy-related complications including GDM, PTB, IUGR, pre-eclampsia, antepartum haemorrhage, cholestasis and caesarean delivery. Model covariates included maternal age, race, insurance status, substance use and medical complications including liver complication, hypertension, HIV, anaemia, thrombocytopenia and sexually transmitted infections. Of 297 664 pregnant women data available for analysis, 1446 had a coded diagnosis of HBV, HCV or both. High-risk behaviours, such as smoking, alcohol and substance use were higher in women with either HBV or HCV. Women with HBV had an increased risk for PTB (aOR 1.65, CI [1.3, 2.0]) but a decreased risk for caesarean delivery (aOR 0.686, CI [0.53, 0.88]). Individuals with HCV had an increased risk for GDM (aOR 1.6, CI [1.0, 2.6]). Individuals with both HBV and HCV co-infection had an increased risk for antepartum haemorrhage (aOR 2.82, CI [1.1, 7.2]). There was no association of viral hepatitis with IUGR or pre-eclampsia. Women with hepatitis have an increased risk for complications during pregnancy. Research to determine the efficacy and cost-effectiveness of counselling patients about potential risks for adverse outcomes is warranted. PMID:21692952

  8. Hepatitis (For Parents)

    MedlinePlus

    ... people at risk for contracting hepatitis. But frequent hand washing and good hygiene practices can reduce this risk. All kids in ... to prevent viral hepatitis you should: Follow good hygiene and avoid crowded, ... their hands thoroughly after using the toilet and before eating. ...

  9. AhR expression and polymorphisms are associated with risk of coronary arterial disease in Chinese population

    PubMed Central

    Huang, Shian; Shui, Xiaorong; He, Yuan; Xue, Yiqiang; Li, Jianwen; Li, Guoming; Lei, Wei; Chen, Can

    2015-01-01

    The aryl hydrocarbon receptor (AhR) mediates the control of environmental toxicity, and modulates the development and pathogenesis of the cardiovascular system. However, little is known about the role of AhR in coronary arterial disease (CAD) susceptibility. We therefore conducted a case-control study in a Chinese population, and assessed the potential association between AhR variants and CAD susceptibility. Compared with the controls, circulating AhR expression was found to be significantly increased in patients with CAD and its subtypes including ST-segment and non-ST-segment elevation myocardial infarction, and stable and unstable angina pectoris. Receiver operating characteristic (ROC) analysis to evaluate the effect of AhR on CAD progression showed it to be a potent biomarker for CAD. Genotype frequencies of AhR rs2066853 differed significantly between CAD and control subjects, while smoking and hyperlipidemia markedly promoted CAD risk relative to the AhR polymorphism. Moreover, a significant difference in AhR variant distribution was observed between the four CAD subtypes with different severities. The expression level and functional polymorphisms of circulating AhR may affect the susceptibility and progression of CAD in Chinese populations. This provides a novel view of the etiology and epidemiology of CAD, and will contribute to the diagnosis and therapy of this severe disease. PMID:25620626

  10. [Update chronic viral hepatitis].

    PubMed

    Ziegenhagen, D J

    2016-03-01

    More than 500,000 people in Germany have chronic viral hepatitis. The interferon-based treatments formerly used in hepatitis B have been widely replaced by life-long oral medication with nucleoside or nucleotide analogues. Treatment for chronic hepatitis C has been improved substantially by the development of new and very expensive drug combinations. Up to 90% of patients can now be cured with certainty, and one to two years after successful treatment there is no relevant risk of recurrence. These individuals expect to receive insurance cover under appropriate conditions. Vaccination programmes are very efficient at decreasing the incidence of hepatitis B, but no vaccine against hepatitis C is likely to become available in the next decade. PMID:27111951

  11. Subchronic Exposure to TCDD, PeCDF, PCB126, and PCB153: Effect on Hepatic Gene Expression

    PubMed Central

    Vezina, Chad M.; Walker, Nigel J.; Olson, James R.

    2004-01-01

    We employed DNA microarray to identify unique hepatic gene expression patterns associated with subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other halogenated aromatic hydrocarbons (HAHs). Female Harlan Sprague-Dawley rats were exposed for 13 weeks to toxicologically equivalent doses of four different HAHs based on the toxic equivalency factor of each chemical: TCDD (100 ng/kg/day), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF; 200 ng/kg/day), 3,3′,4,4′,5-pentachlorobiphenyl (PCB126; 1,000 ng/kg/day), or 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153; 1,000 μg/kg/day). Global gene expression profiles for each exposure, which account for 8,799 gene probe sets contained on Affymetrix RGU34A GeneChips, were compared by principal components analysis. The aryl hydrocarbon receptor (AhR) ligands TCDD, PeCDF, and PCB126 produced very similar global gene expression profiles that were unique from the nonAhR ligand PCB153, underscoring the extensive impact of AhR activation and/or the resulting hepatic injury on global gene expression in female rat liver. Many genes were co-expressed during the 13-week TCDD, PeCDF, or PCB126 exposures, including classical AhR-regulated genes and some genes not previously characterized as being AhR regulated, such as carcinoembryonic-cell adhesion molecule 4 (C-CAM4) and adenylate cyclase-associated protein 2 (CAP2). Real-time reverse-transcriptase polymerase chain reaction confirmed the increased expression of these genes in TCDD-, PeCDF-, and PCB126-exposed rats as well as the up- or down-regulation of several other novel dioxin-responsive genes. In summary, DNA microarray successfully identified dioxin-responsive genes expressed after exposure to AhR ligands (TCDD, PeCDF, PCB126) but not after exposure to the non-AhR ligand PCB153. Together, these findings may help to elucidate some of the fundamental features of dioxin toxicity and may further clarify the biologic role of the AhR signaling pathway. PMID:15598615

  12. Molecular mechanisms of alcoholic liver disease: innate immunity and cytokines.

    PubMed

    Miller, Andrew M; Horiguchi, Norio; Jeong, Won-Il; Radaeva, Svetlana; Gao, Bin

    2011-05-01

    Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases worldwide, causing fatty liver, alcoholic hepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma. In the past few decades, significant progress has been made in our understanding of the molecular mechanisms underlying alcoholic liver injury. Activation of innate immunity components such as Kupffer cells, LPS/TLR4, and complements in response to alcohol exposure plays a key role in the development and progression of alcoholic liver disease (ALD). LPS activation of Kupffer cells also produces IL-6 and IL-10 that may play a protective role in ameliorating ALD. IL-6 activates signal transducer and activator of transcription 3 (STAT3) in hepatocytes and sinusoidal endothelial cells, while IL-10 activates STAT3 in Kupffer cells/macrophages, subsequently protecting against ALD. In addition, alcohol consumption also inhibits some components of innate immunity such as natural killer (NK) cells, a type of cells that play key roles in anti-viral, anti-tumor, and anti-fibrotic defenses in the liver. Ethanol inhibition of NK cells likely contributes significantly to the pathogenesis of ALD. Understanding the roles of innate immunity and cytokines in alcoholic liver injury may provide insight into novel therapeutic targets in the treatment of alcoholic liver disease. PMID:21284667

  13. [Disturbances of folic acid and homocysteine metabolism in alcohol abuse].

    PubMed

    Cylwik, Bogdan; Chrostek, Lech

    2011-04-01

    Chronic alcohol abuse leads to malnutrition, and thus to the deficiency of many nutrients, including vitamins and trace elements. Most often comes to the deficiency of all vitamins, however because the clinical implications, the most important is folic acid (vitamin B9) deficiency. Biochemical effect of folate deficiency is elevated homocysteine concentration in the blood, named "cholesterol of XXI. century". In the paper, the folate and homocysteine metabolism in alcohol abuse was discussed. Mechanisms of alcohol action on folate homeostasis in the human body have been indicated. Chronic alcohol consumption leads to deficiency of this vitamin due to their dietary inadequacy, intestinal malabsorption, decreased hepatic uptake and increased body excretion, mainly via urine. The decreased concentration of serum folic acid may occur in 80% of alcoholics. The cause of elevated concentrations of homocysteine in the serum of alcohol abusers is also a deficiency of vitamins involved such as vitamin B12 and pyridoxal phosphate. Disturbance of folic acid and homocysteine metabolism in alcohol abusers can lead to serious clinical consequences. Folic acid deficiency leads inter alia to macrocytic and megaloblastic anemia and neurological disorders. Megaloblastic anemia occurs in about half of alcohol abusers with chronic liver diseases. In turn, high level of homocysteine in blood is associated with an inreased risk of cardiovascular diseases. Hyperhomocysteinemia is an independent risk factor that favors the occurrence of acute coronary syndromes in patients with coronary heart disease.

  14. Fetal Alcohol Spectrum Disorders.

    PubMed

    Williams, Janet F; Smith, Vincent C

    2015-11-01

    Prenatal exposure to alcohol can damage the developing fetus and is the leading preventable cause of birth defects and intellectual and neurodevelopmental disabilities. In 1973, fetal alcohol syndrome was first described as a specific cluster of birth defects resulting from alcohol exposure in utero. Subsequently, research unequivocally revealed that prenatal alcohol exposure causes a broad range of adverse developmental effects. Fetal alcohol spectrum disorder (FASD) is the general term that encompasses the range of adverse effects associated with prenatal alcohol exposure. The diagnostic criteria for fetal alcohol syndrome are specific, and comprehensive efforts are ongoing to establish definitive criteria for diagnosing the other FASDs. A large and growing body of research has led to evidence-based FASD education of professionals and the public, broader prevention initiatives, and recommended treatment approaches based on the following premises:▪ Alcohol-related birth defects and developmental disabilities are completely preventable when pregnant women abstain from alcohol use.▪ Neurocognitive and behavioral problems resulting from prenatal alcohol exposure are lifelong.▪ Early recognition, diagnosis, and therapy for any condition along the FASD continuum can result in improved outcomes.▪ During pregnancy:◦no amount of alcohol intake should be considered safe;◦there is no safe trimester to drink alcohol;◦all forms of alcohol, such as beer, wine, and liquor, pose similar risk; and◦binge drinking poses dose-related risk to the developing fetus.

  15. Fetal Alcohol Spectrum Disorders.

    PubMed

    Williams, Janet F; Smith, Vincent C

    2015-11-01

    Prenatal exposure to alcohol can damage the developing fetus and is the leading preventable cause of birth defects and intellectual and neurodevelopmental disabilities. In 1973, fetal alcohol syndrome was first described as a specific cluster of birth defects resulting from alcohol exposure in utero. Subsequently, research unequivocally revealed that prenatal alcohol exposure causes a broad range of adverse developmental effects. Fetal alcohol spectrum disorder (FASD) is the general term that encompasses the range of adverse effects associated with prenatal alcohol exposure. The diagnostic criteria for fetal alcohol syndrome are specific, and comprehensive efforts are ongoing to establish definitive criteria for diagnosing the other FASDs. A large and growing body of research has led to evidence-based FASD education of professionals and the public, broader prevention initiatives, and recommended treatment approaches based on the following premises:▪ Alcohol-related birth defects and developmental disabilities are completely preventable when pregnant women abstain from alcohol use.▪ Neurocognitive and behavioral problems resulting from prenatal alcohol exposure are lifelong.▪ Early recognition, diagnosis, and therapy for any condition along the FASD continuum can result in improved outcomes.▪ During pregnancy:◦no amount of alcohol intake should be considered safe;◦there is no safe trimester to drink alcohol;◦all forms of alcohol, such as beer, wine, and liquor, pose similar risk; and◦binge drinking poses dose-related risk to the developing fetus. PMID:26482673

  16. Relaxin-3 Receptor (RXFP3) Signalling Mediates Stress-Related Alcohol Preference in Mice

    PubMed Central

    Walker, Andrew W.; Smith, Craig M.; Chua, Berenice E.; Krstew, Elena V.; Zhang, Cary; Gundlach, Andrew L.; Lawrence, Andrew J.

    2015-01-01

    Stressful life events are causally linked with alcohol use disorders (AUDs), providing support for a hypothesis that alcohol consumption is aimed at stress reduction. We have previously shown that expression of relaxin-3 mRNA in rat brain correlates with alcohol intake and that central antagonism of relaxin-3 receptors (RXFP3) prevents stress-induced reinstatement of alcohol-seeking. Therefore the objectives of these studies were to investigate the impact of Rxfp3 gene deletion in C57BL/6J mice on baseline and stress-related alcohol consumption. Male wild-type (WT) and Rxfp3 knockout (KO) (C57/B6JRXFP3TM1/DGen) littermate mice were tested for baseline saccharin and alcohol consumption and preference over water in a continuous access two-bottle free-choice paradigm. Another cohort of mice was subjected to repeated restraint followed by swim stress to examine stress-related alcohol preference. Hepatic alcohol and aldehyde dehydrogenase activity was assessed in mice following chronic alcohol intake and in naive controls. WT and Rxfp3 KO mice had similar baseline saccharin and alcohol preference, and hepatic alcohol processing. However, Rxfp3 KO mice displayed a stress-induced reduction in alcohol preference that was not observed in WT littermates. Notably, this phenotype, once established, persisted for at least six weeks after cessation of stress exposure. These findings suggest that in mice, relaxin-3/RXFP3 signalling is involved in maintaining high alcohol preference during and after stress, but does not appear to strongly regulate the primary reinforcing effects of alcohol. PMID:25849482

  17. Relaxin-3 receptor (RXFP3) signalling mediates stress-related alcohol preference in mice.

    PubMed

    Walker, Andrew W; Smith, Craig M; Chua, Berenice E; Krstew, Elena V; Zhang, Cary; Gundlach, Andrew L; Lawrence, Andrew J

    2015-01-01

    Stressful life events are causally linked with alcohol use disorders (AUDs), providing support for a hypothesis that alcohol consumption is aimed at stress reduction. We have previously shown that expression of relaxin-3 mRNA in rat brain correlates with alcohol intake and that central antagonism of relaxin-3 receptors (RXFP3) prevents stress-induced reinstatement of alcohol-seeking. Therefore the objectives of these studies were to investigate the impact of Rxfp3 gene deletion in C57BL/6J mice on baseline and stress-related alcohol consumption. Male wild-type (WT) and Rxfp3 knockout (KO) (C57/B6JRXFP3TM1/DGen) littermate mice were tested for baseline saccharin and alcohol consumption and preference over water in a continuous access two-bottle free-choice paradigm. Another cohort of mice was subjected to repeated restraint followed by swim stress to examine stress-related alcohol preference. Hepatic alcohol and aldehyde dehydrogenase activity was assessed in mice following chronic alcohol intake and in naive controls. WT and Rxfp3 KO mice had similar baseline saccharin and alcohol preference, and hepatic alcohol processing. However, Rxfp3 KO mice displayed a stress-induced reduction in alcohol preference that was not observed in WT littermates. Notably, this phenotype, once established, persisted for at least six weeks after cessation of stress exposure. These findings suggest that in mice, relaxin-3/RXFP3 signalling is involved in maintaining high alcohol preference during and after stress, but does not appear to strongly regulate the primary reinforcing effects of alcohol.

  18. Physicochemical properties and surfaces morphologies evaluation of MTA FillApex and AH plus.

    PubMed

    Borges, Álvaro Henrique; Orçati Dorileo, Maura Cristiane Gonçales; Dalla Villa, Ricardo; Borba, Alexandre Meireles; Semenoff, Tereza Aparecida Delle Vedove; Guedes, Orlando Aguirre; Estrela, Cyntia Rodrigues Araújo; Bandeca, Matheus Coelho

    2014-01-01

    The solubility, pH, electrical conductivity, and radiopacity of AH Plus and MTA FillApex were evaluated. In addition, the surfaces morphologies of the sealers were analyzed by using scanning electron microscopy. For pH test, the samples were immersed in distilled water at different periods of time. The same solution was used for electrical conductivity measurement. The solubility and radiopacity were evaluated according to ANSI/ADA. Statistical analyses were carried out at 5% level of significance. MTA FillApex presented higher mean value for solubility and electrical conductivity. No significant difference was observed in the mean values for pH reading. AH Plus presented higher radiopacity mean values. MTA FillApex presented an external surface with porosities and a wide range of sizes. In conclusion, the materials fulfill the ANSI/ADA requirements when considering the radiopacity and solubility. AH Plus revealed a compact and homogeneous surface with more regular aspects and equal particle sizes.

  19. Identification and simulation evaluation of an AH-64 helicopter hover math model

    NASA Technical Reports Server (NTRS)

    Schroeder, J. A.; Watson, D. C.; Tischler, M. B.; Eshow, M. M.

    1991-01-01

    Frequency-domain parameter-identification techniques were used to develop a hover mathematical model of the AH-64 Apache helicopter from flight data. The unstable AH-64 bare-airframe characteristics without a stability-augmentation system were parameterized in the convectional stability-derivative form. To improve the model's vertical response, a simple transfer-function model approximating the effects of dynamic inflow was developed. Additional subcomponents of the vehicle were also modeled and simulated, such as a basic engine response for hover and the vehicle stick dynamic characteristics. The model, with and without stability augmentation, was then evaluated by AH-64 pilots in a moving-base simulation. It was the opinion of the pilots that the simulation was a satisfactory representation of the aircraft for the tasks of interest. The principal negative comment was that height control was more difficult in the simulation than in the aircraft.

  20. Orbital Period Investigations of Two W UMa-type Binaries: AH Aur and V728 Her

    NASA Astrophysics Data System (ADS)

    Yu, Yun-Xia; Xiang, Fu-Yuan; Hu, Ke

    2016-04-01

    The orbital period changes of two W UMa-type binaries, AH Aur and V728 Her, are investigated based on all available times of the light minimum taken from the databases and literature. It is revealed that the orbital period of AH Aur shows a long-term decrease at a rate of {dP}/{dt}=-2.491× {10}-7 days yr-1. For V728 Her, we find that the orbital period exhibits a secular increase at a rate of {dP}/{dt}=3.793× {10}-7 days yr-1. The secular period changes suggest that AH Aur and V728 Her are undergoing rapid mass transfer between the primary star and the secondary companion.

  1. Alcohol Use and Older Adults

    MedlinePlus

    ... version of this page please turn Javascript on. Alcohol Use and Older Adults Alcohol and Aging Adults of any age can have ... Escape (Esc) button on your keyboard.) What Is Alcohol? Alcohol, also known as ethanol, is a chemical ...

  2. Solution structure of the isolated histone H2A-H2B heterodimer.

    PubMed

    Moriwaki, Yoshihito; Yamane, Tsutomu; Ohtomo, Hideaki; Ikeguchi, Mitsunori; Kurita, Jun-Ichi; Sato, Masahiko; Nagadoi, Aritaka; Shimojo, Hideaki; Nishimura, Yoshifumi

    2016-01-01

    During chromatin-regulated processes, the histone H2A-H2B heterodimer functions dynamically in and out of the nucleosome. Although detailed crystal structures of nucleosomes have been established, that of the isolated full-length H2A-H2B heterodimer has remained elusive. Here, we have determined the solution structure of human H2A-H2B by NMR coupled with CS-Rosetta. H2A and H2B each contain a histone fold, comprising four α-helices and two β-strands (α1-β1-α2-β2-α3-αC), together with the long disordered N- and C-terminal H2A tails and the long N-terminal H2B tail. The N-terminal αN helix, C-terminal β3 strand, and 310 helix of H2A observed in the H2A-H2B nucleosome structure are disordered in isolated H2A-H2B. In addition, the H2A α1 and H2B αC helices are not well fixed in the heterodimer, and the H2A and H2B tails are not completely random coils. Comparison of hydrogen-deuterium exchange, fast hydrogen exchange, and {(1)H}-(15)N hetero-nuclear NOE data with the CS-Rosetta structure indicates that there is some conformation in the H2A 310 helical and H2B Lys11 regions, while the repression domain of H2B (residues 27-34) exhibits an extended string-like structure. This first structure of the isolated H2A-H2B heterodimer provides insight into its dynamic functions in chromatin. PMID:27181506

  3. Solution structure of the isolated histone H2A-H2B heterodimer

    PubMed Central

    Moriwaki, Yoshihito; Yamane, Tsutomu; Ohtomo, Hideaki; Ikeguchi, Mitsunori; Kurita, Jun-ichi; Sato, Masahiko; Nagadoi, Aritaka; Shimojo, Hideaki; Nishimura, Yoshifumi

    2016-01-01

    During chromatin-regulated processes, the histone H2A-H2B heterodimer functions dynamically in and out of the nucleosome. Although detailed crystal structures of nucleosomes have been established, that of the isolated full-length H2A-H2B heterodimer has remained elusive. Here, we have determined the solution structure of human H2A-H2B by NMR coupled with CS-Rosetta. H2A and H2B each contain a histone fold, comprising four α-helices and two β-strands (α1–β1–α2–β2–α3–αC), together with the long disordered N- and C-terminal H2A tails and the long N-terminal H2B tail. The N-terminal αN helix, C-terminal β3 strand, and 310 helix of H2A observed in the H2A-H2B nucleosome structure are disordered in isolated H2A-H2B. In addition, the H2A α1 and H2B αC helices are not well fixed in the heterodimer, and the H2A and H2B tails are not completely random coils. Comparison of hydrogen-deuterium exchange, fast hydrogen exchange, and {1H}-15N hetero-nuclear NOE data with the CS-Rosetta structure indicates that there is some conformation in the H2A 310 helical and H2B Lys11 regions, while the repression domain of H2B (residues 27–34) exhibits an extended string-like structure. This first structure of the isolated H2A-H2B heterodimer provides insight into its dynamic functions in chromatin. PMID:27181506

  4. [Influence of ethyl alcohol on diabetes pathogenesis type].

    PubMed

    Zasimowicz, Elzbieta; Wolszczak, Blanka; Zasimowicz, Barbara

    2014-03-01

    Relations between metabolism of carbohydrates and ethyl alcohol consumption became a subject of many research because they occur very frequently amongst alcoholics. One of the most often and dangerous effects of abusing ethanol is hypoglycemia. It is caused by hepatic gluconeogenesis disturbed by ethyl alcohol. Chronic result of abusing alcohol is chronic pancreas inflammation (PZT), what causes disorders of exo- and endocrine function of pancreas. Endocrine function is secretion of insulin and the glucagon what regulates metabolism of absorbed compounds. Failure of beta cells of Langerhans islets causes diabetes demanding insulin therapy. The ethanol can cause recurring diabetes resulting from damage of cells of Langerhans islets but can be also the risk factor of diabetes type 2.

  5. Alcohol and Cancer Risk

    MedlinePlus

    ... Overview Cancer Prevention Overview–for health professionals Research Alcohol and Cancer Risk On This Page What is ... in the risk of colorectal cancer. Research on alcohol consumption and other cancers: Numerous studies have examined ...

  6. Alcohol and Migraine

    MedlinePlus

    ... on Pinterest Follow us on Instagram DONATE TODAY Alcohol and Migraine Abuse, Maltreatment, and PTSD and Their ... to Migraine Altitude, Acute Mountain Sickness and Headache Alcohol and Migraine Anxiety and Depression Caffeine and Migraine ...

  7. Benzyl Alcohol Topical

    MedlinePlus

    Benzyl alcohol lotion is used to treat head lice (small insects that attach themselves to the skin) in adults ... children less than 6 months of age. Benzyl alcohol is in a class of medications called pediculicides. ...

  8. Translational Studies of Alcoholism

    PubMed Central

    Zahr, Natalie M.; Sullivan, Edith V.

    2008-01-01

    Human studies are necessary to identify and classify the brain systems predisposing individuals to develop alcohol use disorders and those modified by alcohol, while animal models of alcoholism are essential for a mechanistic understanding of how chronic voluntary alcohol consumption becomes compulsive, how brain systems become damaged, and how damage resolves. Our current knowledge of the neuroscience of alcohol dependence has evolved from the interchange of information gathered from both human alcoholics and animal models of alcoholism. Together, studies in humans and animal models have provided support for the involvement of specific brain structures over the course of alcohol addiction, including the prefrontal cortex, basal ganglia, cerebellum, amygdala, hippocampus, and the hypothalamic–pituitary–adrenal axis. PMID:20041042

  9. [Neurologic sequelae of alcohol].

    PubMed

    Ladurner, G; Griebnitz, E

    1986-10-10

    The consequences of alcoholism on the peripheral and central nervous system are discussed. Polyneuropathy is present in 30% of the alcoholics, whilst cranial nerve involvement is found in 5-25%. Alcoholic myopathy is only very rarely seen. Wernicke's encephalopathy is found at post mortem investigation in 1.8% of alcoholics, but is rarely clinically diagnosed. The Marchiafava-Bignamy syndrome and central pontine myelinolysis are rarely seen; alcoholic amblyopia which is seen in 0.5% of the hospitalised alcoholics is more frequent, but still a rare finding. Cerebral seizures are common in chronic alcoholics with an incidence varying from 5 to 37% according to the type of drinking habit and have, thus, to be categorised. Brain atrophy is a common finding and correlates with the duration and extent of the alcoholism. PMID:3788182

  10. Alcohol and Cancer

    MedlinePlus

    ... developing some kinds of cancer. The way alcohol causes cancer isn’t completely understood. In fact, there might ... For example, it could be that alcohol itself causes cancer by increasing hormone levels, or it may be ...

  11. Alcohol Calorie Calculator

    MedlinePlus

    ... Alcohol Calorie Calculator Find out the number of beer and hard alcohol calories you are consuming. Simply ... calories) Average Drinks Per Week Monthly Subtotal Calories Beer Regular 12 149 Regular Beer Light 12 110 ...

  12. National Institute on Alcohol Abuse and Alcoholism

    MedlinePlus

    ... TODAY: “Neurodevelopment and Alcohol: From Cell Adhesion to Cell Phones" Dr. Michael Charness, 11/3 @3 , Masur t. ... lecture: “Neurodevelopment and Alcohol: From Cell Adhesion to Cell Phones" Dr. Michael Charness, 11/3 @3 pm, Masur ...

  13. Ah-receptor controlled luciferase expression: A novel species-specific bioassay for Ah-receptor active compounds in environmental matrices

    SciTech Connect

    Murk, A.J.; Aarts, J.M.M.J.G.; Koeman, J.H.; Brouwer, A.; Denison, M.S.

    1995-12-31

    Polyhalogenated aromatic hydrocarbons (PHAHs) such as polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs) are persistent lipophilic compounds that accumulate especially in sediments and in top predators of the aquatic foodchain. PHAHs elicit a number of common toxic responses, which are highly species-specific. The most toxic, planar, PHAHs share a common mechanism of action mediated by the aryl hydrocarbon receptor (AhR). Based on this mechanism, the toxic equivalency factor (TEF) concept has been developed, allowing hazard and risk assessment for mixtures of PHAHs. The TEF-approach assumes additive responses, but also synergistic and antagonistic interactions have been observed. In addition, the often large number of compounds in a mixture, low levels of individual congeners, possible presence of unknown AhR-active substances, and species differences in inducibility, ask for an comprehensive approach in hazard assessment. A number of recombinant cell lines, including Hepa1c1c7 mouse and H411E rat hepatoma cell lines, were developed, showing AhR-mediated firefly (Photinuspyralis) luciferase gene expression. The response by 2,3,7,8-TCDD in the CALUX (chemical activated luciferase expression) assay with these cell lines is dose-dependent, and not subjected to substrate inhibition at higher ligand concentrations. The detection limit for 2,3,7,8-TCDD is below 1 pM (0.2 fmol). The luciferase assay has been successfully applied for monitoring the amount of AhR-active compounds in small aliquots of blood plasma and in both sediment and pore-water samples, of which examples will be presented.

  14. Alcoholic Liver Disease and the Mitochondrial Ribosome

    PubMed Central

    Cahill, Alan; Sykora, Peter

    2009-01-01

    Summary Chronic alcohol consumption has been shown to severely compromise mitochondrial protein synthesis. Hepatic mitochondria isolated from alcoholic animals contain decreased levels of respiratory complexes and display depressed respiration rates when compared to pair-fed controls. One underlying mechanism for this involves ethanol-elicited alterations in the structural and functional integrity of the mitochondrial ribosome. Ethanol feeding results in ribosomal changes that include decreased sedimentation rates, larger hydrodynamic volumes, increased levels of unassociated subunits and changes in the levels of specific ribosomal proteins. The methods presented in this chapter detail how to isolate mitochondrial ribosomes, determine ribosomal activity, separate ribosomes into nucleic acid and protein, and perform two-dimensional nonequilibrium pH gradient electrophoretic polyacrylamide gel electrophoresis to separate and subsequently identify mitochondrial ribosomal proteins. PMID:18369931

  15. Functional and phenotypic effects of AhR activation in inflammatory dendritic cells

    SciTech Connect

    Bankoti, Jaishree; Rase, Ben; Simones, Tom; Shepherd, David M.

    2010-07-15

    Aryl hydrocarbon receptor (AhR) activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces immune suppression. Dendritic cells (DCs) are key antigen presenting cells governing T cell activation and differentiation. However, the consequences of AhR activation in DCs are not fully defined. We hypothesized that AhR activation alters DC differentiation and generates dysfunctional DCs. To test this hypothesis, inflammatory bone marrow-derived DCs (BMDCs) from C57Bl/6 mice were generated in the presence of vehicle or TCDD. TCDD decreased CD11c expression but increased MHC class II, CD86 and CD25 expression on the BMDCs. The effects of TCDD were strictly AhR-dependent but not exclusively DRE-mediated. Similar effects were observed with two natural AhR ligands, 6-formylindolo[3,2-b]carbazole (FICZ) and 2-(1H-Indol-3-ylcarbonyl)-4-thiazolecarboxylic acid (ITE). TCDD increased LPS- and CpG-induced IL-6 and TNF-{alpha} production by BMDCs but decreased their NO production. TCDD decreased CpG-induced IL-12p70 production by BMDCs but did not affect their secretion of IL-10. TCDD downregulated LPS- and CpG-induced NF-kB p65 levels and induced a trend towards upregulation of RelB levels in the BMDCs. AhR activation by TCDD modulated BMDC uptake of both soluble and particulate antigens. Induction of indoleamine-2,3-dioxygenase (IDO) and TGF-{beta}3 has been implicated in the generation of regulatory T cells following AhR activation. TCDD increased IDO1, IDO2 and TGF-{beta}3 mRNA levels in BMDCs as compared to vehicle. Despite the induction of regulatory mediators, TCDD-treated BMDCs failed to suppress antigen-specific T cell activation. Thus, AhR activation can directly alter the differentiation and innate functions of inflammatory DCs without affecting their ability to successfully interact with T cells.

  16. Influenza A/H1N1 Severe Pneumonia: Novel Morphocytological Findings in Bronchoalveolar Lavage

    PubMed Central

    Faverio, Paola; Messinesi, Grazia; Brenna, Ambrogio; Pesci, Alberto

    2014-01-01

    We present the results of bronchoalveolar lavage (BAL) performed in three patients with severe influenza A/H1N1 pneumonia complicated by acute respiratory distress syndrome (ARDS). Light microscopy analysis of BAL cytocentrifugates showed the presence of characteristic large, mononuclear, plasmoblastic/plasmocytoid-like cells never described before. Via transmission electron microscopy, these cells were classified as atypical type II pneumocytes and some of them showed cytoplasmic vesicles and inclusions. We concluded that plasmoblastic/plasmocytoid-like type II pneumocytes might represent a morphologic marker of A/H1N1 influenza virus infection as well as reparative cellular activation after diffuse alveolar damage. PMID:25383078

  17. Physical Parameters of the Overcontact Binary AH Cnc in the Old Open Cluster M 67

    NASA Astrophysics Data System (ADS)

    Yakut, K.; Aerts, C.

    2006-04-01

    We present a photometric study of the overcontact binary AH Cnc. The CCD observations were done with the Russian-Turkish 1.5 m telescope and the light-curve was solved with the Wilson-Devinney code. The physical parameters of the components have been deduced as M1 = 1.22 Msun, M2 = 0.20 Msun, R1 = 1.37 Rsun, R2 = 0.66 Rsun, L1 = 2.65 Lsun and L2 = 0.63 Lsun from the obtained orbital parameters and the distance modules of M 67. AH Cnc has been compared with similar systems in the Hertzsprung-Russell diagram.

  18. Alcohol and motorcycle fatalities.

    PubMed Central

    Baker, S P; Fisher, R S

    1977-01-01

    A series of 99 fatal motorcycle crashes in Maryland was studied retrospectively, using police and medical examiner records. Blood alcohol concentrations were determined for 62 motorcycle drivers; measurable amounts of alcohol were found in two-thirds (41), and one-half (31) had illegally high concentrations of 100 mg/100 ml or more. The police report mentioned alcohol in only 9 instances. High blood alcohol concentrations were found most commonly among drivers age 20-34. PMID:842762

  19. The Alcoholism Questionnaire.

    ERIC Educational Resources Information Center

    Ferneau, E.; Mueller, S.

    The alcoholism questionnaire used to survey college student attitudes on the subject is provided. It is identical to the drug-abuse questionnaire except for word changes appropriate to the subject matter. The questionnaire consists of 40 statements about alcoholics and alcoholism, with 7 possible responses: (1) completely disagree; (2) mostly…

  20. Youths' Perceptions of Alcoholism.

    ERIC Educational Resources Information Center

    Lorch, Barbara (Day); Hughes, Robert H.

    1986-01-01

    Only a third of students in this study accepted the medical model of alcoholism. Those who had the least knowledge of, and experience with, alcohol were the most likely to consider alcoholism as an illness. The source of information on drugs most conducive to acceptance of the medical model was parents. (Author/ABB)

  1. Alcohol and Minority Youth.

    ERIC Educational Resources Information Center

    Wright, Roosevelt, Jr.; Watts, Thomas D.

    1991-01-01

    Maintains that minority youth who use (or abuse) alcohol in American society deal with using alcohol, being minority, and being young, three dimensions viewed by society with mixed, sometimes hostile and/or fearful reactions. Suggests that examining alcoholism among minority youth involves coming to grips with poverty, education, income, and life…

  2. Television: Alcohol's Vast Adland.

    ERIC Educational Resources Information Center

    2002

    Concern about how much television alcohol advertising reaches underage youth and how the advertising influences their attitudes and decisions about alcohol use has been widespread for many years. Lacking in the policy debate has been solid, reliable information about the extent of youth exposure to television alcohol advertising. To address this…

  3. Alcohol on Campus.

    ERIC Educational Resources Information Center

    ACU-I Bulletin, 1984

    1984-01-01

    Alcohol use on campus and strategies colleges are using to educate students about alcohol are considered in two articles. In "When Alternatives Aren't," Ruth Bradford Burnham and Stephen J. Nelson explore the role alcoholic beverages play in young people's social lives and some of the implications for planning social events. They offer a balanced…

  4. Biological Vulnerability to Alcoholism.

    ERIC Educational Resources Information Center

    Schuckit, Marc A.

    1987-01-01

    Reviews the role of biological factors in the risk for alcoholism. Notes the importance of the definition of primary alcoholism and highlights data indicating that this disorder is genetically influenced. In studies of men at high risk for the future development of alcoholism, vulnerability shows up in reactions to ethanol brain wave amplitude and…

  5. Adult Children of Alcoholics.

    ERIC Educational Resources Information Center

    Goodman, Ronald W.

    1987-01-01

    Presents analysis of adult children of alcoholics, their experience and adjustment in relation to the severity and type of alcoholism, age considerations and perceptions as a child, and existence and nature of significant others. Discusses alcoholics' and others' family issues, focusing on roles taken, and personality characteristics. Emphasizes…

  6. Alcoholism and Lesbians

    ERIC Educational Resources Information Center

    Gedro, Julie

    2014-01-01

    This chapter explores the issues involved in the relationship between lesbianism and alcoholism. It examines the constellation of health and related problems created by alcoholism, and it critically interrogates the societal factors that contribute to the disproportionately high rates of alcoholism among lesbians by exploring the antecedents and…

  7. Alcoholism's Hidden Curriculum.

    ERIC Educational Resources Information Center

    Gress, James R.

    1988-01-01

    Discusses children of alcoholics as victims of fetal alcohol syndrome, family violence, retarded social development, and severe emotional scars. These children bring family roles to school that allow survival in the alcoholic home but are dysfunctional outside it. Educators can take certain steps to address these students' problems. Includes six…

  8. Women and Alcohol

    MedlinePlus

    ... alcohol, which is found in: »» 12 ounces of beer with 5 percent alcohol content »» 5 ounces of wine with 12 percent alcohol content »» 1.5 ounces ... reflect customary serving sizes. A large cup of beer, an overpoured glass of wine, or a single ...

  9. Alcohol and the elderly.

    PubMed

    Dufour, M C; Archer, L; Gordis, E

    1992-02-01

    Moderate drinking for the elderly of both genders is no more than one drink per day, where a drink is defined as 12 oz of beer, 5 oz of wine, or 1.5 oz of spirits. Age does not affect the rate of absorption or elimination of alcohol. Lean body mass decreases and adipose tissue increases with age, however, resulting in a corresponding decrease in the volume of total body water. With a smaller volume of distribution, an alcohol dose identical to that administered to a younger individual of the same size and gender will produce a higher blood alcohol concentration in the elderly. Low-dose alcohol stimulates appetite and promoters regular bowel function. In the well-nourished nonalcoholic elderly, the negative impact of alcohol consumption on nutrition is minimal. Alcohol consumption improves mood by increasing feelings of happiness and freedom from care while lessening inhibitions, stress, tension, and depression. Although in the laboratory low-dose alcohol improves certain types of cognitive function in young men, in other types of task performance, alcohol induces impairment, which worsens with age. The effects of alcohol on sleep are primarily detrimental, worsening both insomnia and breathing disturbances during sleep. Although the role of alcohol consumption in mortality from heart disease has not been investigated in the elderly, moderate drinking appears safe. Under some circumstances low-dose alcohol may produce analgesia whereas in others it may worsen pain. The elderly use a significant proportion of both prescription and over-the-counter medication, a large variety of which interact with alcohol. Alcoholic beverage consumption may exacerbate cognitive impairment and dementias of other etiology. Although some studies suggest that moderate use of alcohol by institutionalized senior citizens appears to produce benefits including improved socialization, separation of the effects of the social situation from those specifically attributable to alcohol remains to

  10. Experimental models of hepatic fibrosis in the rat.

    PubMed

    Wasser, S; Tan, C E

    1999-01-01

    The rat is a frequently used experimental model in studies involving human disease. We review several methods of inducing hepatic fibrosis and cirrhosis in rats. These include induction by hepatotoxins and hepatocarcinogens such as carbon tetrachloride, dimethylnitrosamine, thioacetamide and furan; the hepatoxin-cum-nutrient, alcohol; a high fat-low choline-low protein diet; immunologic agents such as heterologous serum or bacterial cell wall products; and obstructive jaundice and biliary cirrhosis by common bile duct ligation. PMID:10374036

  11. Circadian clock control of hepatic lipid metabolism: role of small heterodimer partner (Shp).

    PubMed

    Wang, Li; Liangpunsakul, Suthat

    2016-10-01

    Hepatic steatosis, the accumulation of triglyceride droplets in the hepatocytes, is a common hepatic pathology seen in subjects with obesity/metabolic syndrome and those with excessive alcohol use. The pathogenesis underlying hepatic steatosis is complex. Recent studies have shown the specific role played by the molecular clock mechanism in the control of lipid metabolism and that the disruption of these tissue clocks may lead to the disturbances in lipid homeostasis. This review reports a novel role of small heterodimer partner in maintaining triglyceride and lipoprotein homeostasis through neuronal PAS domain protein 2. PMID:27473715

  12. The hepatitis C crisis.

    PubMed

    St John, Tina M; Sandt, Lorren

    2005-01-01

    An estimated 170 million persons (3% of the world's population) are infected with the hepatitis C virus (HCV), and 3 to 4 million persons are newly infected each year. Of those infected, 70%-85% develop chronic viremia with the potential for devastating long-term sequelae, including chronic liver disease, cirrhosis, hepatic failure, and hepatocellular carcinoma. The passivity in the public health sector and in the medical community at large with respect to hepatitis C portends a myriad of societal, fiscal, and personal costs for the United States within the next two decades unless immediate actions are taken to intervene in the natural history of this emerging public health crisis. PMID:15822840

  13. Chronic Alcohol Ingestion in Rats Alters Lung Metabolism, Promotes Lipid Accumulation, and Impairs Alveolar Macrophage Functions

    PubMed Central

    Romero, Freddy; Shah, Dilip; Duong, Michelle; Stafstrom, William; Hoek, Jan B.; Kallen, Caleb B.; Lang, Charles H.

    2014-01-01

    Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung diseases, including infectious pneumonia and acute respiratory distress syndrome. Although alcoholism has been shown to alter hepatic metabolism, leading to lipid accumulation, hepatitis, and, eventually, cirrhosis, the effects of alcohol on pulmonary metabolism remain largely unknown. Because both the lung and the liver actively engage in lipid synthesis, we hypothesized that chronic alcoholism would impair pulmonary metabolic homeostasis in ways similar to its effects in the liver. We reasoned that perturbations in lipid metabolism might contribute to the impaired pulmonary immunity observed in people who chronically consume alcohol. We studied the metabolic consequences of chronic alcohol consumption in rat lungs in vivo and in alveolar epithelial type II cells and alveolar macrophages (AMs) in vitro. We found that chronic alcohol ingestion significantly alters lung metabolic homeostasis, inhibiting AMP-activated protein kinase, increasing lipid synthesis, and suppressing the expression of genes essential to metabolizing fatty acids (FAs). Furthermore, we show that these metabolic alterations promoted a lung phenotype that is reminiscent of alcoholic fatty liver and is characterized by marked accumulation of triglycerides and free FAs within distal airspaces, AMs, and, to a lesser extent, alveolar epithelial type II cells. We provide evidence that the metabolic alterations in alcohol-exposed rats are mechanistically linked to immune impairments in the alcoholic lung: the elevations in FAs alter AM phenotypes and suppress both phagocytic functions and agonist-induced inflammatory responses. In summary, our work demonstrates that chronic alcohol ingestion impairs lung metabolic homeostasis and promotes pulmonary immune dysfunction. These findings suggest that therapies aimed at reversing alcohol-related metabolic alterations might be effective for preventing and

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

    PubMed

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

    2014-12-01

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

  15. Chemically-induced formation of an inhibitor of hepatic uroporphyrinogen decarboxylase in inbred mice with iron overload.

    PubMed Central

    Smith, A G; Francis, J E

    1987-01-01

    An inhibitor of hepatic uroporphyrinogen decarboxylase (EC 4.1.1.37) was demonstrated in heat-treated extracts of livers from C57BL/10ScSn mice with iron overload after a single dose (100 mg/kg; 350 mumol/kg) of hexachlorobenzene (HCB). Inhibition was not due to accumulated uroporphyrin since this could be removed by a SEP-PAK C18 cartridge without affecting inhibitor activity. The presence of the inhibitor could be first demonstrated 2 weeks after mice received HCB and before major elevation of hepatic porphyrin levels. Maximum inhibitory potential was reached at about 8 weeks and was still detected 25 weeks after the chemical, thus paralleling the depression of enzyme activity reported previously [Smith, Francis, Kay, Greig & Stewart (1986) Biochem. J. 238, 871-878]. The inhibitor was not detected following treatment of mice with either iron or HCB alone or after the decarboxylase activity was destroyed in vitro by the combination of uroporphyrin and light. The formation of the inhibitor by inbred mouse strains nominally Ah-responsive (C57BL/6J, C57BL/10ScSn, BALB/c, C3H/HeJ, CBA/J and A/J) and Ah-nonresponsive (SWR, AKR, 129, SJL, LP and DBA/2) did not correlate fully with their reported Ah-phenotype. There was a correlation amongst the Ah-responsive strains only, with hepatic ethoxyphenoxazone de-ethylase activity induced in parallel experiments by treatment with beta-naphthoflavone. De-ethylase activity induced by HCB, however, was considerably less than that with beta-naphthoflavone, which has not been reported as porphyrogenic. Other polyhalogenated chemicals, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,4,2',3',4'-hexachlorobiphenyl and hexabromobenzene, also caused the formation of the inhibitor of uroporphyrinogen decarboxylase. PMID:3675556

  16. Nicotinic acid supplementation in the context of alcoholic liver injury: friend or foe?

    PubMed

    Kharbanda, Kusum K

    2014-07-01

    Li and colleagues (2014) in this issue report that dietary nicotinic acid (NA) supplementation ameliorates ethanol-induced hepatic steatosis, but a deficiency does not worsen injury induced by alcohol alone. The authors further present some mechanistic insights into the protective role of NA supplementation. Results of this and other previous studies in the context of alcoholic liver injury raise one important question as to what should be an adequate dose of NA that will provide the maximum benefit to hepatic and extrahepatic tissues and with minimum adverse effects.

  17. 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 ...

  18. Gene cloning and expression analysis of AhR and CYP4 from Pinctada martensii after exposed to pyrene.

    PubMed

    Du, Junqiao; Liao, Chenghong; Zhou, Hailong; Diao, Xiaoping; Li, Yuhu; Zheng, Pengfei; Wang, Fuqiang

    2015-10-01

    Pyrene, a typical polycyclic aromatic hydrocarbon, is a common pollutant in the marine environment. Polycyclic aromatic hydrocarbons initiate cellular detoxification in an exposed organism via the activation of the aryl hydrocarbon receptor (AhR). Subsequent metabolism of these xenobiotics is mainly by the cytochrome P450 enzymes of the phase I detoxification system. Full-length complementary DNA sequences from the pearl oyster Pinctada martensii (pm) encoding AhR and cytochrome P4 were cloned. The P. martensii AhR complementary DNA sequence constitutes an open reading frame that encodes for 848 amino acids. Sequence analysis indicated PmAhR showed high similarity with its homologues of other bivalve species. The cytochrome P(CYP)4 complementary DNA sequence of P. martensii constitutes an open reading frame that encodes for 489 amino acids. Quantitative real-time analysis detected both PmAhR and PmCYP4 messenger RNA expressions in the mantle, gill, hepatapancreas and adductor muscle of P. martensii exposed to pyrene. The highest transcript-band intensities of PmAhR and PmCYP4 were observed in the gill. Temporal expression of PmAhR and PmCYP4 messenger RNAs induction was observed in gills and increased between 3 and 5 days post exposure; then returned to control level. These results suggest that messenger RNAs of PmAhR and PmCYP4 in pearl oysters might be useful parameters for monitoring marine environment pyrene pollution.

  19. Arylhydrocarbon receptor (AhR) activation in airway epithelial cells induces MUC5AC via reactive oxygen species (ROS) production.

    PubMed

    Chiba, Takahito; Uchi, Hiroshi; Tsuji, Gaku; Gondo, Hisaki; Moroi, Yoichi; Furue, Masutaka

    2011-02-01

    The dioxins and dioxin-like compounds in cigarette smoke regulate various immunological responses via the arylhydrocarbon receptor (AhR). These environmental toxicants are known to cause bronchitis, asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. Recent studies have demonstrated that AhR activation upregulates the expression of mucin 5AC, oligomeric mucus/gel-forming (MUC5AC) in the airway epithelial cell line. However, the mechanism for the production of mucin has not been clarified. In this study, we investigated the role and pathway of AhR in airway epithelial cells by using selective agonists and antagonists. After stimulation with or without benzopyrene (B[a]P), an AhR agonist, MUC5AC expression was measured by real-time RT-PCR. The mechanism of AhR-induced MUC5AC expression in airway epithelial cells was studied in terms of the production of cytokine and reactive oxygen species (ROS). Treatment with B[a]P increased ROS generation in NCI-H₂₉₂ cells. Furthermore, B[a]P-induced MUC5AC upregulation and mucin production were inhibited by AhR siRNA or the use of an antioxidative agent. These results suggest that the AhR-induced increase of mucin production is partially mediated by ROS generation. An antioxidant therapy approach may help to cure AhR-induced mucus hypersecretory diseases. PMID:20709182

  20. Hepatic sarcoidosis complicating treatment-naive viral hepatitis

    PubMed Central

    Aravinthan, Aloysious; Gelson, William; Limbu, Anita; Brais, Rebecca; Richardson, Paul

    2012-01-01

    Hepatic sarcoidosis is usually asymptomatic but rarely leads to adverse liver-related outcome. Co-existence of viral hepatitis and hepatic sarcoidosis is a rare, but recognised phenomenon. Obtaining a balance between immune suppression and anti-viral therapy may be problematic. Immunosuppression in the presence of viral hepatitis can lead to rapid deterioration of liver disease. Similarly, anti-viral therapy may exacerbate granulomatous hepatitis. Here we present two cases of viral hepatitis co-existing with sarcoidosis that illustrate successful management strategies. In one, hepatitis B replication was suppressed with oral anti-viral therapy before commencing prednisolone. In the second, remission of hepatic sarcoidosis was achieved with prednisolone, before treating hepatitis C and obtaining a sustained virological response with pegylated interferon and ribavirin therapy. PMID:23355920