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  1. Acute Ethanol Gavage Attenuates Hemorrhage/Resuscitation-Induced Hepatic Oxidative Stress in Rats

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    B. Relja

    2012-01-01

    Full Text Available Acute ethanol intoxication increases the production of reactive oxygen species (ROS. Hemorrhagic shock with subsequent resuscitation (H/R also induces ROS resulting in cellular and hepatic damage in vivo. We examined the role of acute ethanol intoxication upon oxidative stress and subsequent hepatic cell death after H/R. 14 h before H/R, rats were gavaged with single dose of ethanol or saline (5 g/kg, EtOH and ctrl; H/R_EtOH or H/R_ctrl, resp.. Then, rats were hemorrhaged to a mean arterial blood pressure of 30±2 mmHg for 60 min and resuscitated. Two control groups underwent surgical procedures without H/R (sham_ctrl and sham_EtOH, resp.. Liver tissues were harvested at 2, 24, and 72 h after resuscitation. EtOH-gavage induced histological picture of acute fatty liver. Hepatic oxidative (4-hydroxynonenal, 4-HNE and nitrosative (3-nitrotyrosine, 3-NT stress were significantly reduced in EtOH-gavaged rats compared to controls after H/R. Proapoptotic caspase-8 and Bax expressions were markedly diminished in EtOH-gavaged animals compared with controls 2 h after resuscitation. EtOH-gavage increased antiapoptotic Bcl-2 gene expression compared with controls 2 h after resuscitation. iNOS protein expression increased following H/R but was attenuated in EtOH-gavaged animals after H/R. Taken together, the data suggest that acute EtOH-gavage may attenuate H/R-induced oxidative stress thereby reducing cellular injury in rat liver.

  2. Steroidogenic acute regulatory protein (StAR) overexpression attenuates HFD-induced hepatic steatosis and insulin resistance.

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    Qiu, Yanyan; Sui, Xianxian; Zhan, Yongkun; Xu, Chen; Li, Xiaobo; Ning, Yanxia; Zhi, Xiuling; Yin, Lianhua

    2017-04-01

    Non-alcoholic fatty liver disease (NAFLD) covers a wide spectrum of liver pathology. Intracellular lipid accumulation is the first step in the development and progression of NAFLD. Steroidogenic acute regulatory protein (StAR) plays an important role in the synthesis of bile acid and intracellular lipid homeostasis and cholesterol metabolism. We hypothesize that StAR is involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. The hypothesis was identified using free fatty acid (FFA)-overloaded NAFLD in vitro model and high-fat diet (HFD)-induced NAFLD mouse model transfected by recombinant adenovirus encoding StAR (StAR). StAR expression was also examined in pathology samples of patients with fatty liver by immunohistochemical staining. We found that the expression level of StAR was reduced in the livers obtained from fatty liver patients and NAFLD mice. Additionally, StAR overexpression decreased the levels of hepatic lipids and maintained the hepatic glucose homeostasis due to the activation of farnesoid x receptor (FXR). StAR overexpression attenuated the impairment of insulin signaling in fatty liver. This protective role of StAR was owing to a reduction of intracellular diacylglycerol levels and the phosphorylation of PKCε. Furthermore, FXR inactivation reversed the observed beneficial effects of StAR. The present study revealed that StAR overexpression can reduce hepatic lipid accumulation, regulate glucose metabolism and attenuate insulin resistance through a mechanism involving the activation of FXR. Our study suggests that StAR may be a potential therapeutic target for NAFLD.

  3. Prolonged acute hepatitis A mimicking autoimmune hepatitis

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    Rintaro Mikata; Osamu Yokosuka; Fumio Imazeki; Kenichi Fukai; Tatsuo Kanda; Hiromitsu Saisho

    2005-01-01

    AIM: We report a case with a prolonged course of hepatitisA, with alanine aminotransferase (ALT) higher than 500 IU/Lfor more than 2 mo.METHODS: A middle-aged woman had an elevated IgG level of more than 2 000 mg/dL, positive arti-nudear antibodies (ANA) and anti-smooth muscle antibodies (ASMA), but no evidence of persistent hepatitis A virus (HAV) infection. Liver biopsy findings were compatible with prolonged acute hepatitis, although acute onset of autoimmune hepatitis could not be ruled out.RESULTS: It was assumed that she developed a course of hepatitis similar to autoimmune hepatitis triggered by HAV infection. Ursodeoxycholic acid (UDCA) treatment was initiated and a favorable outcome was obtained. CONCLUSION: We describe a case of a middle-aged woman who showed a prolonged course of acute hepatitis A mimicking autoimmune hepatitis. Treatment with UDCAproved to be effective.

  4. Acute pancreatitis in acute viral hepatitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To elucidate the frequency and characteristics of pancreatic involvement in the course of acute (nonfulminant) viral hepatitis.METHODS: We prospectively assessed the pancreatic involvement in patients with acute viral hepatitis who presented with severe abdomimanl pain.RESULTS: We studied 124 patients with acute viral hepatitis, of whom 24 presented with severe abdominal pain. Seven patients (5.65%) were diagnosed to have acute pancreatitis. All were young males. Five patients had pancreatitis in the first week and two in the fourth week after the onset of jaundice. The pancreatitis was mild and all had uneventful recovery from both pancreatitis and hepatitis on conservative treatment.The etiology of pancreatitis was hepatitis E virus in 4,hepatitis A virus in 2, and hepatitis B virus in 1 patient.One patient had biliary sludge along with HEV infection.The abdominal pain of remaining seventeen patients was attributed to stretching of Glisson's capsule.CONCLUSION: Acute pancreatitis occurs in 5.65% of patients with acute viral hepatitis, it is mild and recovers with conservative management.

  5. Management of acute hepatitis B.

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    Shiffman, Mitchell L

    2010-02-01

    Acute hepatitis B virus (HBV) is a common cause of acute icteric hepatitis in adults. The vast majority of these patients resolve this acute infection and develop long-lasting immunity. In contrast, the vast majority of patients who develop chronic HBV have minimal symptoms and do not develop jaundice after becoming infected with HBV. These patients will frequently remain undiagnosed for years or decades. Approximately 1% of persons with acute HBV develop acute liver failure. Preventing acute HBV with vaccination is the best treatment. Although universal vaccination is now administered to newborns in many countries, the majority of adults have not been vaccinated and remain at risk. Because the majority of patients with acute HBV resolve this infection spontaneously, treatment with an oral anti-HBV agent is not necessary. However, the use of an oral anti-HBV agent is not unreasonable to use in a patient who is developing acute liver failure from severe acute HBV.

  6. Autoimmune hepatitis triggered by acute hepatitis A

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    Hiroto Tanaka; Hiroto Tujioka; Hiroki Ueda; Hiroko Hamagami; Youhei Kida; Masakazu Ichinose

    2005-01-01

    The patient was a 57-year-old woman presenting with jaundice as the chief complaint. She began vomiting on July 10, 2003.Jaundice was noted and admitted to our hospital for thorough testing. Tests on admission indicated severe hepatitis, based on: aspartate aminotransferase (AST), 1 076 IU/L; alanine aminotransferase (ALT), 1 400 IU/L; total bilirubin (TB), 20.9 mg/dL; and prothrombin time rate (PT%), 46.9%. Acute hepatitis A (HA) was diagnosed based on negative hepatitis B surface antigen and hepatitis C virus RNA and positive immunoglobulin (Ig) M HA antibody, but elevation of anti-nuclear antigen (×320) and IgG (3 112 mg/dL) led to suspicion of autoimmune hepatitis (AIH). Plasma exchange was performed for 3 d from July 17, and steroid pulse therapy was performed for 3 d starting on July 18, followed by oral steroid therapy. Liver biopsy was performed on August 5, and the results confirmed acute hepatitis and mild chronic inflammation. Levels of AST and ALT normalized,so dose of oral steroid was markedly reduced. Steroid therapy was terminated after 4 mo, as the patient had glaucoma. Starting 3 mo after cessation of steroid therapy,levels of AST and ALT began to increase again. Another liver biopsy was performed and AIH was diagnosed based on serum data and biopsy specimen. Oral steroid therapy was reinitiated. Levels of AST and ALT again normalized.The present case was thus considered to represent AIH triggered by acute HA.

  7. Studies on acute hepatic insufficiency

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    G.H. de Groot (Gerrit Harmen)

    1984-01-01

    textabstractAcute hepatic failure (AHF) is one of the most dramatic situations that a clinical physician can encounter. It is also one of the most frustating since death is the result in a large majority of the cases, despite all efforts of the medical and nursing staffs. Although a wide variety of

  8. Oxymatrine liposome attenuates hepatic fibrosis via targeting hepatic stellate cells

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    Ning-Li Chai; Qiang Fu; Hui Shi; Chang-Hao Cai; Jun Wan; Shi-Ping Xu; Ben-Yan Wu

    2012-01-01

    AIM:To investigate the potential mechanism of ArgGly-Asp (RGD) peptide-labeled liposome loading oxymatrine (OM) therapy in CCl4-induced hepatic fibrosis in METHODS:We constructed a rat model of CCl4-induced hepatic fibrosis and treated the rats with different formulations of OM.To evaluate the antifibrotic effect of OM,we detected levels of alkaline phosphatase,hepatic histopathology (hematoxylin and eosin stain and Masson staining) and fibrosis-related gene expression of matrix metallopeptidase (MMP)-2,tissue inhibitor of metalloproteinase (TIMP)-1 as well as type Ⅰ procollagen via quantitative real-time polymerase chain reaction.To detect cell viability and apoptosis of hepatic stellate cells (HSCs),we performed 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide assay and flow cytometry.To reinforce the combination of oxymatrine with HSCs,we constructed fluorescein-isothiocyanate-conjugated Arg-Gly-Asp peptide-labeled liposomes loading OM,and its targeting of HSCs was examined by fluorescent microscopy.RESULTS:OM attenuated CCl4-induced hepatic fibrosis,as defined by reducing serum alkaline phosphatase (344.47 ± 27.52 U/L vs 550.69 ± 43.78 U/L,P < 0.05),attenuating liver injury and improving collagen deposits (2.36% ± 0.09% vs 7.70% ± 0.60%,P < 0.05) and downregulating fibrosis-related gene expression,that is,MMP-2,TIMP-1 and type Ⅰ procollagen (P < 0.05).OM inhibited cell viability and induced apoptosis of HSCs in vitro.RGD promoted OM targeting of HSCs and enhanced the therapeutic effect of OM in terms of serum alkaline phosphatase (272.51 ± 19.55 U/L vs 344.47 ± 27.52 U/L,P < 0.05),liver injury,collagen deposits (0.26% ± 0.09% vs 2.36% ± 0.09%,P < 0.05) and downregulating fibrosis-related gene expression,that is,MMP-2,TIMP-1 and type Ⅰ procollagen (P < 0.05).Moreover,in vitro assay demonstrated that RGD enhanced the effect of OM on HSC viability and apoptosis.CONCLUSION:OM attenuated hepatic fibrosis by

  9. Acute hepatic encephalopathy with diffuse cortical lesions

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    Arnold, S.M.; Spreer, J.; Schumacher, M. [Section of Neuroradiology, Univ. of Freiburg (Germany); Els, T. [Dept. of Neurology, University of Freiburg (Germany)

    2001-07-01

    Acute hepatic encephalopathy is a poorly defined syndrome of heterogeneous aetiology. We report a 49-year-old woman with alcoholic cirrhosis and hereditary haemorrhagic telangiectasia who developed acute hepatic coma induced by severe gastrointestinal bleeding. Laboratory analysis revealed excessively elevated blood ammonia. MRI showed lesions compatible with chronic hepatic encephalopathy and widespread cortical signal change sparing the perirolandic and occipital cortex. The cortical lesions resembled those of hypoxic brain damage and were interpreted as acute toxic cortical laminar necrosis. (orig.)

  10. Acute hepatitis with nontyphoidal salmonella and hepatitis E virus coinfection

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    Yu-Ting Kuo

    2014-09-01

    Full Text Available A 65-year-old Taiwanese man presented with dark urine for 5 days before admission to hospital and with fever on the 2nd day of admission to hospital. Laboratory studies showed acute hepatitis with hyperbilirubinemia. Acute hepatitis with nontyphoidal salmonella and hepatitis E virus coinfection was diagnosed. The fever subsided after treatment with ceftriaxone and cefepime. His serum bilirubin reached its peak value on the 3rd week after admission to hospital and then gradually returned to the normal range. To the best of our knowledge, acute hepatitis E coinfection with nontyphoidal salmonella has not been reported previously.

  11. Acute hepatitis C: Prospects and challenges

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    More than 170 million people worldwide have chronic hepatitis C. Acute hepatitis C is rarely diagnosed because it is commonly asymptomatic. Most infected patients are unaware of their condition until the symptoms of chronic infection manifest. Treatment of acute hepatitis C is something of a paradox because spontaneous resolution is possible and many patients do not have symptoms.However, several factors provide a rationale for treating patients who have acute hepatitis C. Compared with acute hepatitis C, chronic hepatitis C is associated with a worse prognosis, the need for more intensive treatment,longer treatment duration, and a decrease in successful treatment outcomes. Conversely, early intervention is associated with improved viral eradication, using a regimen that is better tolerated, less expensive, more convenient, and of shorter duration than the currently approved combination therapies for chronic hepatitis C.

  12. Acute pericarditis and renal failure complicating acute hepatitis A infection.

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    Beyazit, Yavuz; Guven, Gulay Sain; Kekilli, Murat; Koklu, Seyfettin; Yolcu, Omer Faruk; Shorbagi, Ali

    2006-01-01

    Hepatitis A infection may result in acute hepatitis, and rarely, fulminant hepatitis may ensue. Extrahepatic manifestations of hepatitis A are uncommon. The authors present the case of a 77-year-old male who had development of acute renal failure and pericarditis during the clinical course of acute hepatitis A infection. He died as a result of septic shock on the fifth day of hospitalization. To the best of our knowledge, this is the first report of both these rare and serious complications appearing in the same patient.

  13. Pediatric knowledge about acute viral hepatitis

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    Franca,Rita; Silva,Luciana; Melo, Maria Clotildes; Cavalcante,Suzy; Lima, Bruno; Rocha, Anita; Gomes, Cristiana; Franca, Mônica

    2004-01-01

    p.227-235 Knowledge about hepatotropic viruses is crucial for pediatricians because of the high prevalence of viral hepatitis during childhood. The multiplicity of hepatotropic viruses, the spectrum of acute and chronic infections, and the sequels of viral hepatitis result in a need for physicians to better understand the clinical and epidemiological context of patients with viral hepatitis, as well as the importance of prevention measures for hepatitis. A descriptive cross-sectional study...

  14. Characteristics of hepatitis viruses among Egyptian children with acute hepatitis.

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    Youssef, Ahmed; Yano, Yoshihiko; El-Sayed Zaki, Maysaa; Utsumi, Takako; Hayashi, Yoshitake

    2013-04-01

    Hepatitis viral infection is hyperendemic in Egypt, western Asia and Africa. However, little is known about the status of hepatitis viruses among rural Egyptian children. Therefore, this study sought to examine the prevalence and characteristics of hepatitis viruses among symptomatic Egyptian children. Serological and molecular analyses of hepatitis viral infection were conducted in 33 children hospitalised at Mansoura University with symptomatic hepatic dysfunction (mean ± standard deviation age, 9.7±3.4 years; alanine aminotransferase level, 130±68 IU/ml). Eleven children (33%) were positive for anti-haemagglutination-IgM and were diagnosed with acute hepatitis A. Hepatitis B surface antigen (HBsAg) and anti‑hepatitis C virus (HCV) were detected in 9 (27%) and 7 (21%) children, respectively, indicating acute-on-chronic infection with hepatitis viruses. None of the children was positive for anti‑hepatitis B core antigen-IgM. Phylogenetic analysis confirmed that all HBVs belonged to genotype D (subgenotype D1) and that HCV belonged to genotypes 4a and 1g. HBV-DNA was detected in 9 children (27%) in the pre-S/S region and in 16 children (48%) in the core promoter/precore region. The Y134F amino acid mutation in the 'α' determinant region was detected in all of the patients. The A1762T/G1764A double mutation, and the T1846A and G1896A single mutations were common in children with occult HBV infection. In conclusion, hepatitis viral infection, including acute-on-chronic infection with HCV and HBV, is common in Egyptian children hospitalised with acute hepatitis.

  15. Fulminant hepatic failure (FHF) due to acute hepatitis C.

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    Younis, Bilal Bin; Arshad, Rozina; Khurhsid, Saima; Masood, Junaid; Nazir, Farhan; Tahira, Maham

    2015-01-01

    Acute hepatitis C (HCV) infection has been identified as an important cause of fulminant hepatic failure (FHF), characterized by rapid deterioration of liver function from massive hepatic necrosis leading to encephalopathy and multi-organ failure. We admitted a female patient at Shalamar Hospital with jaundice, fever, encephalopathy and coagulopathy of short duration with no history of any comorbidity. Her hepatitis viral screen revealed positive anti HCV. Her viral loads were also high. A diagnosis of FHF due to acute HCV infection was made. Patient was treated conservatively and improved gradually. In summary, acute HCV can cause FHF and should be ruled out in patients with FHF of unknown cause in an endemic country for HCV like Pakistan.

  16. NNDSS - Table II. Hepatitis (viral, acute) C

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    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) C - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  17. NNDSS - Table II. Hepatitis (viral, acute)

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    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) - 2014.In this Table, all conditions with a 5-year average annual national total of more than or equals 1,000 cases but...

  18. NNDSS - Table II. Hepatitis (viral, acute)

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    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) - 2016. In this Table, provisional* cases of selected†notifiable diseases (≥1,000 cases reported during the preceding...

  19. NNDSS - Table II. Hepatitis (viral, acute)

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  20. Acute abdomen caused by brucellar hepatic abscess.

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    Ibis, Cem; Sezer, Atakan; Batman, Ali K; Baydar, Serkan; Eker, Alper; Unlu, Ercument; Kuloglu, Figen; Cakir, Bilge; Coskun, Irfan

    2007-10-01

    Brucellosis is a zoonotic infection that is transmitted from animals to humans by ingestion of infected food products, direct contact with an infected animal, or aerosol inhalation. The disease is endemic in many countries, including the Mediterranean basin, the Middle East, India, Mexico, Central and South America and, central and southwest Asia. Human brucellosis is a systemic infection with a wide clinical spectrum. Although hepatic involvement is very common during the course of chronic brucellosis, hepatic abscess is a very rare complication of Brucella infection. We present a case of hepatic abscess caused by Brucella, which resembled the clinical presentation of surgical acute abdomen.

  1. Albendazole-induced associated acute hepatitis and bicytopenia.

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    Ben Fredj, Nadia; Chaabane, Amel; Chadly, Zohra; Ben Fadhel, Najeh; Boughattas, Naceur A; Aouam, Karim

    2014-02-01

    Acute hepatitis induced by albendazole is rarely reported. We describe herein an original case of acute hepatitis associated with bicytopenia after albendazole intake. This paper is the first to describe a possible association of a hematologic disorder and acute hepatitis, both induced by albendazole therapy.

  2. Does chronic hepatitis B infection affect the clinical course of acute hepatitis A?

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    Shin, Su Rin; Moh, In Ho; Jung, Sung Won; Kim, Jin Bae; Park, Sang Hoon; Kim, Hyoung Su; Jang, Myung Kuk; Lee, Myung Seok

    2013-01-01

    The impact of chronic hepatitis B on the clinical outcome of acute hepatitis A remains controversial. The aim of present study was to evaluate the clinical characteristics of acute hepatitis A in cases with underlying chronic hepatitis B compared to cases of acute hepatitis A alone. Data on 758 patients with acute hepatitis A admitted at two university-affiliated hospitals were reviewed. Patients were classified into three groups: group A, patients with both acute hepatitis A and underlying chronic hepatitis B (n = 27); group B, patients infected by acute hepatitis A alone whose sexes and ages were matched with patients in group A (n  = 54); and group C, patients with acute hepatitis A alone (n = 731). None of the demographic features of group A were significantly different from those of group B or C, except for the proportion of males and body weight, which differed from group C. When comparing to group B, clinical symptoms were more frequent, and higher total bilirubin and lower albumin levels were observed in group A. When comparing to group C, the albumin levels were lower in group A. There were no differences in the duration of hospital stay, occurrence of acute kidney injury, acute liver failure, prolonged cholestasis, or relapsing hepatitis. This study revealed that clinical symptoms and laboratory findings were less favorable for patients with acute hepatitis A and chronic hepatitis B compared to those with acute hepatitis A alone. However, there were no differences in fatal outcomes or serious complications.

  3. Acute Hepatitis Induced by Alpha-Interferon in a Patient with Chronic Hepatitis C

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    Ivan Kraus; Dinko Vitezic

    2001-01-01

    Hepatic adverse effects occur very rarely with alpha-interferon therapy. A case of acute hepatitis induced by alpha-interferon in a 33-year-old man with chronic hepatitis C is described. The patient developed acute hepatitis with very high aminotransferase activity and jaundice. After discontinuing alpha-interferon therapy, hepatitis resolved rapidly. The immune-mediated mechanism is the most probable cause of this hepatitis.

  4. Acute Hepatitis Induced by Alpha-Interferon in a Patient with Chronic Hepatitis C

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    Ivan Kraus

    2001-01-01

    Full Text Available Hepatic adverse effects occur very rarely with alpha-interferon therapy. A case of acute hepatitis induced by alpha-interferon in a 33-year-old man with chronic hepatitis C is described. The patient developed acute hepatitis with very high aminotransferase activity and jaundice. After discontinuing alpha-interferon therapy, hepatitis resolved rapidly. The immune-mediated mechanism is the most probable cause of this hepatitis.

  5. Impaired plasma lipid profiles in acute hepatitis

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    Wang Yongzhong

    2010-01-01

    Full Text Available Abstract The present study examined plasma lipid profiles in thirty patients suffered from acute viral hepatitis. Patients' blood samples were collected at both the debut and recovery of diseases. Thirty sex and age matched normal subjects were included as controls. Plasma total triglycerides (TG, total cholesterol, high density lipoprotein cholesterol (HDL-C, low density lipoprotein cholesterol (LDL-C, apolipoprotein AI (ApoAI, apolipoprotein B (ApoB, lipoprotein (a (Lp(a, blood coagulation status including prothrombin complex activity and activated partial tromboplastin time (APTT, and hepatic functions were determined by the automatic biochemical analytical instrument. It demonstrated that plasma levels of total cholesterol, HDL-C and apoAI were significantly lower in the patients at the acute phase of hepatitis than those in normal subjects, whereas plasma levels of TG and LDL-C were obviously higher in the patients than in normal subjects (P

  6. Ischaemic Markers in Acute Hepatic Injury

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    Jena, Sushanta Kumar; Nanda, Rachita; Mangaraj, Manaswini; Nayak, Parsuram

    2016-01-01

    Introduction Hepatic injury of varied aetiology may progress to Acute Liver Failure (ALF). Compromised microcirculation is thought to be a deciding factor of hepatic hypoxia may be involved in disease progression that needs early detection. Ischaemia markers like serum Ischaemia- modified albumin (IMA), ALT-LDH ratio and ALT-LDH index have been suggested for its detection at early stage. Aim To find out the association of Ischaemia markers like serum IMA, ALT-LDH ratio and ALT-LDH index in acute hepatic injury cases. Materials and Methods Forty one diagnosed acute liver injury cases of varied aetiology admitted in Department of Medicine, and Gastroenterology of SCB Medical College, Cuttack were enrolled in the study along with 30 age and sex matched healthy controls. Blood collected at time of admission and at time of discharge (1st day and 7th day) were evaluated for FPG, RFT, LFT, Serum Albumin along with serum LDH, IMA, PT-INR and platelet count. Result Serum bilirubin, hepatic enzymes, IMA, PT-INR was more markedly raised in cases than controls on the 1st day of admission. ALT-LDH ratio and index were significantly low in complicated cases. However, on responding to treatment the ALT-LDH index on 7th day registered a rise in comparison to the 1st day, while serum IMA revealed an insignificant decline showing improvement in hepatic hypoxia. ALT-LDH ratio remains more or less same on response to treatment. Conclusion Serum IMA and ALT-LDH Index reveals association with disease process in Acute Hepatic Injury cases both clinically and biochemically and can be used as supportive parameters for the diagnosis of disease process. PMID:27190791

  7. Cerebral edema associated with acute hepatic failure.

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    Fujiwara,Masachika

    1985-02-01

    Full Text Available The clinicopathological findings of cerebral edema were investigated in patients with acute hepatic failure autopsied at Okayama University Hospital between 1970 and 1980 retrospectively. Nine (64% of 14 hepatic failure cases were found to have cerebral edema during a post-mortem examination of the brain. Clinical features of the patients with cerebral edema were not significantly different from those of the patients without cerebral edema. However, general convulsions were observed more frequently in patients later found to have cerebral edema. Moreover, the length of time from deep coma to death was much shorter in the brain edema cases with cerebral herniation than without herniation.

  8. Acute Brucellar Hepatitis: Report of Two Cases

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    Keramat

    2015-05-01

    Full Text Available Introduction Brucellosis is a common zoonotic disease which has a wide spectrum of clinical manifestations and complications in humans. Brucellosis is an endemic disease in Iran. The aim of this case report was to introduce acute hepatitis as a rare complication of acute brucellosis. Case Presentation First case, a 25-year-old man, who complained from fever, chillness, nocturnal sweating, nausea, vomiting, jaundice, and right upper quadrant pain, and was admitted to the hospital. Laboratory tests showed a five-fold increase in alanine aminotransferase and aspartate aminotransferase levels, and increased total and direct bilirubin and alkaline phosphatase levels. Second case, a 63-year-old man, who complained from fever, chillness, weight loss, malaise and nocturnal sweating, and was admitted to the hospital. Laboratory tests showed an eight-fold increase in alanine aminotransferase and aspartate aminotransferase levels, and increased total and direct bilirubin and alkaline phosphatase levels. The patient had jaundice at the third day of admission. The results of seroagglutination tests, Wright and 2-mercaptoethanol (2ME were positive for both patients. The patients were diagnosed as having acute brucella hepatitis and were treated with standard regimen of anti-brucella drugs and improved completely after six weeks of treatment. Conclusions Brucellosis must be considered in the differential diagnosis of acute hepatitis in patients with jaundice and fever manifestations especially if there is a history of unpasteurized dairy products ingestion and life in endemic areas because early diagnosis and treatment of the patient can decrease complications and mortality rate.

  9. Acute hepatitis C in patients receiving hemodialysis.

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    Griveas, I; Germanidis, G; Visvardis, G; Morice, Y; Perelson, A S; Pawlotsky, J M; Papadopoulou, D

    2007-01-01

    Hepatitis C virus (HCV) infection is frequent in patients with end-stage renal disease treated by chronic dialysis, with a prevalence varying from 10-65% according to the geographical data. The prevalence is significantly associated with the duration of dialysis and the number of transfused blood products[1,2] and has dramatically declined with efficient blood screening.[3] We studied patients with acute HCV infection in a dialysis unit. The diagnosis was based on both anti-HCV detection and HCV-RNA detection. Other virological tools including HCV genotype determination was also used to tailor treatment to the individual patient and determine its efficacy for a one-year follow-up period. Seventeen patients (7 male and 10 female, mean age: 63.7 +/- 11.6 SD) with acute hepatitis C were enrolled to our study. All of them were followed up for a period of one year after the diagnosis was established. Phylogenetic analysis distinguished two separate HCV subtypes 1b, which were both responsible for this acute infection (see Figure 1). These types did not differ in their behavior on the clinical situation of our patients, as confirmed by the fact that in both groups of patients, there was only one patient who presented with acute illness. Six patients of our study group, three months after the acute infection, received pegylated interferon (Peg-IFNa2a) 135 mug for a six-month period. Four of them responded very well to therapy and at the first determination HCV RNA was below the cutoff point. One of our patients with very high HCV levels (HCV RNA > 50,000,000 IU/mL), despite receiving the same therapy, did not respond well and developed cirrhosis. In conclusion, it is clear from our experience that better information is needed about the current incidence, prevalence, and risk factors for HCV infection in dialysis patients. Algorithms for the diagnosis and management of hepatitis C should be developed by academic societies. Routine screening for hepatitis C also would allow

  10. Alverine citrate induced acute hepatitis

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    Mehmet Arhan; Seyfettin K(o)klü; Aydln S K(o)ksal; (O)mer F Yolcu; Senem Koruk; Irfan Koruk; Ertugrul Kayacetin

    2004-01-01

    Alverine citrate is a commonly used smooth muscle relaxant agent. A MEDLINE search on January 2004 revealed only 1 report implicating the hepatotoxicity of this agent. A 34-year-old woman was investigated because of the finding of elevated liver function tests on biochemical screening. Other etiologies of hepatitis were appropriately ruled out and elevated enzymes were ascribed to alverine citrate treatment.Although alverine citrate hepatotoxicity was related to an immune mechanism in the first case, several features such as absence of predictable dose-dependent toxicity of alverine citrate in a previous study and absence of hypersensitivity manifestations in our patient are suggestive of a metabolic type of idiosyncratic toxicity.

  11. Clearance of HCV RNA following acute hepatitis A superinfection.

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    Cacopardo, B; Nunnari, G; Nigro, L

    2009-05-01

    A transient reduction of hepatitis C virus replication during the course of acute hepatitis A virus infection has already been reported in the literature. The present study reports the case study of a subject with chronic hepatitis due to hepatitis C virus who went on to develop an acute hepatitis A. From the early onset of acute disease, hepatitis C virus ribonucleic acid became undetectable. Following recovery from acute hepatitis, alanine amino-transferase levels became persistently normal and liver biopsy revealed a reduction in the Knodell histological activity index score. Hepatitis C virus ribonucleic acid clearance was maintained up to 4 years after the onset of acute hepatitis A. During the course of the acute disease, a sharp increase in interferon gamma levels was detected in serum and in the supernatant of both unstimulated and phytoemagglutinin/lipopolysaccharide-stimulated peripheral blood mononuclear cells. Interferon gamma levels were still high 3 months later. We hypothesize that acute hepatitis A virus superinfection during the course of chronic hepatitis C may lead to hepatitis C virus ribonucleic acid clearance through an immunological mechanism related to interferon gamma production.

  12. Clindamycin-induced acute cholestatic hepatitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    We report a case of acute hepatotoxicity in a 42-yearold woman after administration of clindamycin for a dental infection. After 6 d of treatment, she had fatigue, nausea, vomiting, anorexia, pruritus and jaundice. Her laboratory analysis showed alanine aminotransferase (ALT), 1795 IU/L (normal range 0-40); aspartate aminotransferase (AST), 1337 IU/L (normal range 5-34); alkaline phosphatase (ALP), 339 IU/L (normal range 40-150); γ-glutamyl transpeptidase (GGT), 148 IU/L (normal range 9-64 IU/L); total bilirubin, 4.1 mg/dL; direct bilirubin, 2.9 mg/dL and prothrombin time (PT), 13.5 s, with international normalized ratio (INR), 1.04. She was hospitalized, with immediate drug discontinuation. Her liver biopsy specimen showed mixed-type (both hepatocellular and cholestatic) hepatic injury, compatible with a diagnosis of drug-induced hepatitis. An objective causality assessment using the Naranjo probability scale suggested that clindamycin was the probable cause of the acute hepatitis. In susceptible individuals, clindamycin use may lead to acute mixedtype liver toxicity. Complete recovery may be possible if the drug is discontinued before severe liver injury is established.

  13. Acute pancreatitis, acute hepatitis and acute renal failure favourably resolved in two renal transplant recipients.

    Science.gov (United States)

    Voiculescu, Mihai; Ionescu, Camelia; Ismail, Gener; Mandache, Eugen; Hortopan, Monica; Constantinescu, Ileana; Iliescu, Olguta

    2003-03-01

    Renal transplantation is often associated with severe complications. Except for acute rejection, infections and toxicity of immunosuppressive treatment are the most frequent problems observed after transplantation. Infections with hepatic viruses (HBV, HDV, HCV, HGV) and cytomegalic virus (CMV) are the main infectious complications after renal transplantation. Cyclosporine toxicity is not unusual for a patient with renal transplantation and is even more frequent for patients with hepatic impairment due to viral infections. The subjects of this report are two renal transplant recipients with acute pancreatitis, severe hepatitis and acute renal failure on graft, receiving immunosuppressive therapy for maintaining renal graft function

  14. Acute hepatitis due to dengue virus in a chronic hepatitis patient

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    Souza, L J; Coelho, J.M.C. de O.; Silva,E. J.; Abukater,M.; Almeida,F.C.R.; A. S. Fonte; L.A Souza

    2008-01-01

    We present a case of acute hepatitis caused by dengue virus, with a significant increase in aspartate transferase and alanine transferase levels in a chronic hepatitis patient attended at the Cane Sugar Planters Hospital of Campos dos Goytacazes, RJ.

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

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    Y. Wan

    2014-08-01

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

  16. Acute hepatitis due to brucellosis: case report

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    Nevil AYKIN

    2009-06-01

    Full Text Available Brucella infection is a systemic disease. It rarely causes local infections like hepatitis in gastrointestinal system. In this article we would like to present an acute hepatitis case related to brucella infection that followed up in our clinic. A male, 30 year-old patient hospitalized due to common muscle pain, high fever and vomiting. During the physical examination the patient’s skin, scleras and mucosal membranes were icteric, the liver was 2-3 cm palpable and tender. Laboratory findings were as follows: AST:1190 U/L; ALT:715 U/L; GGT:961 U/L; ALP:369 U/L; total bilirubin:4.6 mg/dL; direct bilirubin:2.1 mg/dL. Viral markers were found to be negative. We started treatment with streptomicine and doxicycline since, the patient’s standard brucella tube agglutination test was positive (1/60 and brucella spp produced in his blood culture. From the second day of the treatment, we started to get clinical response. On the 17th day of the treatment, he discharged from the hospital because ALT, AST and bilirubine level were found normal and his treatment was completed to the 8 weeks. Brucella is continuing to be an important health problem especially who live in surrounding countryside and have to keep in mind in the differential diagnosis of the acute hepatitis.

  17. Histological and immunohistochemical features in fatal acute fulminant hepatitis E

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    Vinita Agrawal

    2012-01-01

    Full Text Available Background: Hepatitis E is being increasingly recognized as an emerging infection in developed countries. Data on histological findings and nature of inflammatory cell infiltrate in liver in this disease are quite sparse. Aims: This study was planned to study the histological features and the type of inflammatory infiltrate in liver biopsies of patients with acute fulminant hepatitis E. Materials and Methods: We retrieved postmortem liver biopsies of 11 Indian patients with fulminant hepatitis E, and compared these with biopsies from seven patients with fulminant hepatitis B. Results : Biopsies from acute fulminant hepatitis E showed varying degrees of hepatocyte necrosis, mixed portal and lobular inflammation, accompanied by bile ductular proliferation, lymphocytic cholangitis, Kupffer cell prominence, cholestasis, apoptotic bodies, pseudo-rosette formation, steatosis, and presence of plasma cells in portal tracts. Interface hepatitis was more frequent in acute hepatitis B than in acute hepatitis E (100% vs 20%; P<0.05. These findings differ from those reported in cases with autochthonous hepatitis E in Europe. On immunohistochemistry, lymphocyte infiltrate consisted predominantly of CD3 + T cells in both hepatitis E and hepatitis B; these cells contained a predominant cytotoxic (CD8 + cell subpopulation in 81.8% of cases with hepatitis E and in 50% of cases with hepatitis B. Conclusion: Our findings suggest that histological changes in HEV infection may vary with geographical location because of prevalent HEV genotypes, and that CD8 + lymphocytes play a role in HEV-induced liver injury.

  18. Acute Brucella Hepatitis in an Urban Patient

    Directory of Open Access Journals (Sweden)

    Seyed Moayed Alavian

    2009-11-01

    Full Text Available A 35-year-old man was referred to our center because of low grade fever, vomiting, yellow sclera, and tenderness in the upper-right quadrant of his abdomen. Laboratory tests showed a white blood cell (WBC of 7100/µL, a platelet of 184,000/µL, an erythrocyte sedimentation rate (ESR of 4 mm/h, an alanine aminotransferase (ALT of 525 U/L, an aspartate aminotransferase AST of 142 U/L, a total bilirubin level of 4.23 mg/dL, and a direct bilirubin level of 3.16 mg/dL. Viral hepatitis markers, immunoglobuline M antibody to cytomegalovirus (anti-CMV IgM, Ebstein-Barr virus (EBV IgM, and immunologic markers of autoimmune hepatitis were negative. The patient was diagnosed with acute hepatitis. Alkaline phosphatase was in the normal range throughout the course of the disease. Because of the patient's occupation as a butcher and his history of eating semi-cooked sheep testes, serologic tests of brucellosis were conducted; the tests came out positive. We were concerned about the hepatotoxicity of standard regimens; therefore, we started treatment with streptomycin and ciprofloxacin regimens. Although liver enzyme had fallen and fever discontinued, the total and direct bilirubin concentrations in the patient's serum both increased in spite of using 2 weeks of the abovementioned drug regimen. The elevation of bilirubin could have been due to drug hepatotoxicity. Alternatively, a regimen containing ciprofloxacin may have not have been efficient enough and may have had effects on the direct bilirubin concentration. Fortunately, within 8 weeks, progressive recovery was noticed. Brucellosis should be considered in the differential diagnosis of fever and hepatitis for those who live in endemic areas, especially if his/her job was at high risk for acquiring brucellosis. We recommend taking a careful occupational and behavioral history for patients with acute hepatitis syndrome. We assumed that ciprofloxacin was not suitable for brucella hepatitis treatment and

  19. Identification of acute self-limited hepatitis B among patients presenting with hepatitis B virus-related acute hepatitis: a hospital-based epidemiological and clinical study.

    Science.gov (United States)

    Han, Y-N

    2009-01-01

    This study aimed to identify acute self-limited hepatitis B (ASL-HB) among patients presenting with hepatitis B virus (HBV)-related acute hepatitis. Data were available for 220 patients diagnosed with HBV-related acute hepatitis, of whom 164 had acute hepatitis B (AHB). Of these, 160 were confirmed as ASL-HB: three (1.9%) evolved to chronic hepatitis B and one (0.6%) developed fulminant hepatitis and died. Comparisons were also made between AHB and acute infections with hepatitis A (HA) and hepatitis E (HE) viruses. During the study period, the number of patients with AHB exceeded the sum of those with acute HA and acute HE infections. There was no distinct seasonal peak for AHB infection, whereas both acute HA and acute HE infections occurred more frequently in the spring. Clinical symptoms and physical signs were similar for all three types of hepatitis, but significant differences were seen in some biochemical parameters. In conclusion, this study suggests that symptomatic AHB is not rare in China but it seldom evolves to chronic hepatitis B.

  20. CT findings of hepatic abscess arising from perforated acute cholecystitis

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Sang Hee; Lee, Kyoung Soo; Lee, Jin Seoung; Lee, Moon Gyu; Chung, Young Hwa; Lee, Young Sang; Lee, Sung Gyu; Auh, Yong Ho [Ulsan Univ. College of Medicine, Seoul (Korea, Republic of)

    1996-01-01

    The purpose of this study was to report the CT findings of four patients with hepatic abscess secondary to perforated acute cholecystitis. We retrospectively reviewed the CT findings of four patients with surgically proven hepatic abscess secondary to perforated acute cholecystitis. CT findings were analysed with respect to the observation of the gallbladder, pericholecystic space, hepatic lesions, and peritoneal cavity. All patients underwent cholecystectomy, with drainage of the hepatic abscess. CT findings of hepatic abscess secondary to perforated acute cholecystitis were hypodense mass formation in the pericholecystic space(n=3), irreguarity and wall defect of Gallbladder(n=4), thickened Gallbladder wall(n=4), stone with debris(n=4), and local or diffuse infiltration of the pericholecystic area(n=3), omentum, and mesentery. CT was helpful in diagnosing the hepatic abscess secondary to perforated acute cholecystitis.

  1. A case of acute viral hepatitis interfering with acute fatty liver disease of pregnancy

    Directory of Open Access Journals (Sweden)

    Abdulkadir Turgut

    2013-03-01

    Full Text Available Acute hepatitis A is a rarely seen infection during pregnancy.In terms of clinical and laboratory findings, it can beinterfere with acute fatty liver disease which can be quitemortal during pregnancy. Since liver function tests are elevatedin both conditions, hepatitis A infection should alsobe kept in mind in differential diagnosis. We present a 30year-old pregnant woman with 35 weeks of gestation whopresented to our clinic with a suspection of acute fattyliver disease but finally diagnosed as acute hepatitis A infection.J Clin Exp Invest 2013; 4 (1: 123-125Key words: Hepatitis A, pregnancy, acute fatty liver disease

  2. Acute Hepatitis and Pancytopenia in Healthy Infant with Adenovirus

    Directory of Open Access Journals (Sweden)

    Amr Matoq

    2016-01-01

    Full Text Available Adenoviruses are a common cause of respiratory infection, pharyngitis, and conjunctivitis in infants and young children. They are known to cause hepatitis and liver failure in immunocompromised patients; they are a rare cause of hepatitis in immunocompetent patients and have been known to cause fulminant hepatic failure. We present a 23-month-old immunocompetent infant who presented with acute noncholestatic hepatitis, hypoalbuminemia, generalized anasarca, and pancytopenia secondary to adenovirus infection.

  3. Endogenous n-3 polyunsaturated fatty acids attenuate T cell-mediated hepatitis via autophagy activation

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    Yanli Li

    2016-09-01

    Full Text Available Omega-3 polyunsaturated fatty acids (n-3 PUFAs exert anti-inflammatory effects in several liver disorders, including cirrhosis, acute liver failure, and fatty liver disease. To date, little is known about their role in immune-mediated liver diseases. In this study, we used fat-1 transgenic mice rich in endogenous n-3 PUFAs to examine the role of n-3 PUFAs in immune-mediated liver injury. Concanavalin A (Con A was administered intravenously to wild-type (WT and fat-1 transgenic mice to induce T cell-mediated hepatitis. Reduced liver damage was shown in Con A-administrated fat-1 transgenic mice, as evidenced by decreased mortality, attenuated hepatic necrosis, lessened serum alanine aminotransferase (ALT activity, and inhibited production of pro-inflammatory cytokines (e.g. TNF-α, IL-6, IL-17A and IFN-γ. In vivo and in vitro studies demonstrated that n-3 PUFAs significantly inhibited the activation of hepatic T cells and the differentiation of Th1 cells after Con A challenge. Further studies showed that n-3 PUFAs markedly increased autophagy level in Con A-treated fat-1 T cells compared with the WT counterparts. Blocking hepatic autophagy activity with chloroquine diminished the differences in T cell activation and liver injury between Con A-injected WT and fat-1 transgenic mice. We conclude that n-3 PUFAs limit Con A-induced hepatitis via an autophagy-dependent mechanism, and could be exploited as a new therapeutic approach for autoimmune hepatitis.

  4. Endogenous n-3 Polyunsaturated Fatty Acids Attenuate T Cell-Mediated Hepatitis via Autophagy Activation

    Science.gov (United States)

    Li, Yanli; Tang, Yuan; Wang, Shoujie; Zhou, Jing; Zhou, Jia; Lu, Xiao; Bai, Xiaochun; Wang, Xiang-Yang; Chen, Zhengliang; Zuo, Daming

    2016-01-01

    Omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert anti-inflammatory effects in several liver disorders, including cirrhosis, acute liver failure, and fatty liver disease. To date, little is known about their role in immune-mediated liver diseases. In this study, we used fat-1 transgenic mice rich in endogenous n-3 PUFAs to examine the role of n-3 PUFAs in immune-mediated liver injury. Concanavalin A (Con A) was administered intravenously to wild-type (WT) and fat-1 transgenic mice to induce T cell-mediated hepatitis. Reduced liver damage was shown in Con A-administrated fat-1 transgenic mice, as evidenced by decreased mortality, attenuated hepatic necrosis, lessened serum alanine aminotransferase activity, and inhibited production of pro-inflammatory cytokines (e.g., TNF-α, IL-6, IL-17A, and IFN-γ). In vivo and in vitro studies demonstrated that n-3 PUFAs significantly inhibited the activation of hepatic T cells and the differentiation of Th1 cells after Con A challenge. Further studies showed that n-3 PUFAs markedly increased autophagy level in Con A-treated fat-1 T cells compared with the WT counterparts. Blocking hepatic autophagy activity with chloroquine diminished the differences in T cell activation and liver injury between Con A-injected WT and fat-1 transgenic mice. We conclude that n-3 PUFAs limit Con A-induced hepatitis via an autophagy-dependent mechanism and could be exploited as a new therapeutic approach for autoimmune hepatitis. PMID:27679638

  5. Hydrogen sulfide, a potential novel drug, attenuates concanavalin A-induced hepatitis

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    Cheng P

    2014-09-01

    Full Text Available Ping Cheng,* Kan Chen,* Yujing Xia, Weiqi Dai, Fan Wang, Miao Shen, Chengfen Wang, Jing Yang, Rong Zhu, Huawei Zhang, Jingjing Li, Yuanyuan Zheng, Junshan Wang, Yan Zhang, Jie Lu, Yingqun Zhou, Chuanyong GuoDepartment of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University of Medicine, Shanghai, People's Republic of China *These authors contributed equally to this work Background: Hydrogen sulfide (H2S is known to exert anti-inflammatory properties. Apoptosis and autophagy play important roles in concanavalin A (Con A-induced acute hepatitis. The purpose of this study was to explore both the effect and mechanism of H2S on Con A-induced acute hepatitis. Methods: BALB/c mice were randomized into sham group, Con A-injection group, and 14 µmol/kg of sodium hydrosulfide (NaHS, an H2S donor pretreatment group. Results: Aspartate aminotransferase, alanine aminotransferase, and pathological damage were significantly ameliorated by NaHS pretreatment. NaHS pretreatment significantly reduced the levels of interleukin-6 and tumor necrosis factor-α compared with those of the Con A group. The expression of Bcl-2, Bax, Beclin-1, and LC3-2, which play important roles in the apoptosis and autophagy pathways, were also clearly affected by NaHS. Furthermore, NaHS affected the p-mTOR and p-AKT. Conclusion: H2S attenuates Con A-induced acute hepatitis by inhibiting apoptosis and autophagy, in part, through activation of the PtdIns3K-AKT1 signaling pathway. Keywords: NaHS, apoptosis, PtdIns3K-AKT, autophagy

  6. NNDSS - Table II. Hepatitis (viral, acute) A & B

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) A & B - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

  7. Rosmarinic acid attenuates hepatic ischemia and reperfusion injury in rats.

    Science.gov (United States)

    Ramalho, Leandra Naira Z; Pasta, Ângelo Augusto C; Terra, Vânia Aparecida; Augusto, Marlei Josiele; Sanches, Sheila Cristina; Souza-Neto, Fernando P; Cecchini, Rubens; Gulin, Francine; Ramalho, Fernando Silva

    2014-12-01

    Rosmarinic acid (RosmA) demonstrates antioxidant and anti-inflammatory properties. We investigated the effect of RosmA on liver ischemia/reperfusion injury. Rats were submitted to 60 min of ischemia plus saline or RosmA treatment (150 mg/kg BW intraperitoneally) followed by 6 h of reperfusion. Hepatocellular injury was evaluated according to aminotransferase activity and histological damage. Hepatic neutrophil accumulation was also evaluated. Oxidative/nitrosative stress was estimated by measuring the reduced glutathione, lipid hydroperoxide and nitrotyrosine levels. Endothelial and inducible nitric oxide synthase (eNOS/iNOS) and nitric oxide (NO) were assessed with immunoblotting and chemiluminescence assays. Hepatic tumor necrosis factor-alpha (TNF-α) and interleukin-1beta mRNA were assessed using real-time PCR, and nuclear factor-kappaB (NF-κB) activation was estimated by immunostaining. RosmA treatment reduced hepatocellular damage, neutrophil infiltration and all oxidative/nitrosative stress parameters. RosmA decreased the liver content of eNOS/iNOS and NO, attenuated NF-κB activation, and down-regulated TNF-α and interleukin-1beta gene expression. These data indicate that RosmA exerts anti-inflammatory and antioxidant effects in the ischemic liver, thereby protecting hepatocytes against ischemia/reperfusion injury. The mechanisms underlying these effects may be related to the inhibitory potential of RosmA on the NF-κB signaling pathway and the reduction of iNOS and eNOS expressions and NO levels, in addition to its natural antioxidant capability.

  8. Acute Cholestatic Hepatitis Associated with Teucrium Polium

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    M Mohammadi

    2007-12-01

    Full Text Available Diabetes mellitus (DM is a metabolic disorder resulting from a defect in Insulin secretion, insulin action or both. Despite the fact that it has a worldwide high prevalence, morbidity and mortality, it is regarded as a non–curable but controllable disease. In addition to different synthetic drugs, plant remedies and dietary traditions play an effective role in treatment. Teucrium polium L. is one of the 300 species of the genus Teucrium and found mainly in the Mediterranean and Western lrano- Turanian sphere. lt is widely distributed in Jordan and Palestine. The leaves, 1-3 cm long, are sessile, oblong or linear, the stems are ending in shortly paniculate or corymbose inflorescences, and corolla is white or pale cream colored. This case describes a 74year old man with diabetes since 20 years. He was treated by glibenclamide 5mg/day. He stopped this drug and started daily consumption of tea containing the medicinal plant, teucrium polium. One month after initiation of this therapy, he developed an acute icteric hepatitis like illness. After 8 weeks, the patient recovered clinically and bilirubin, ALT and AST levels were normal.

  9. [A study of 158 cases of acute delta hepatitis].

    Science.gov (United States)

    Castro, A; Buti, M; Esteban, R; Jardí, R; Allende, H; Roget, M; Rodríguez-Frías, F; Guardia, J

    1990-09-22

    We have prospectively studied 158 cases of acute hepatitis delta observed during the last 7 years in a general hospital. Among them 136 were male and 22 female. The mean age was 22.7 years with a range between 16 and 61 years. The epidemiologic factors were drug addiction by parenteral route in 145 cases (92%), sexual transmission in 5 (3%), post transfusional in 2 (1%) and unknown in 6 (4%). With respect to the delta type infection, 105 cases (66%) were coinfections with type B and delta, and 53 patients had a type delta superinfection (34%). The clinical course was a fulminant hepatitis in three cases (two cases of coinfection B and delta an one case of delta superinfection), and an acute benign hepatitis in 155 patients. The follow-up of 118 patients revealed that 96% of coinfections by type B and delta evolved to the chronicity showing findings of active chronic hepatitis or hepatic cirrhosis. It should be noted that in 4 cases of superinfection delta type (11%) the HBsAg was negative after several months of positivity. In these patients the level of transaminases normalized and the hepatic histology evidenced alterations of chronic active hepatitis (2 cases) and hepatic cirrhosis (2 cases) without identification of tissular delta antigen.

  10. Telmisartan attenuates hepatic fibrosis in bile duct-ligated rats

    Institute of Scientific and Technical Information of China (English)

    En-tong YI; Rui-xia LIU; Yan WEN; Cheng-hong YIN

    2012-01-01

    Aim: To evaluate the antifibrotic effect of telmisartan,an angiotensin Ⅱ receptor blocker,in bile duct-ligated rats.Methods: Adult Sprague-Dawley rats were allocated to 3 groups: sham-operated rats,model rats underwent common bile duct ligation (BDL),and BDL rats treated with telmisartan (8 mg/kg,po,for 4 weeks).The animals were sacrificed on d 29,and liver histology was examined,the Knodell and Ishak scores were assigned,and the expression of angiotensin-converting enzyme (ACE) and ACE2 was evaluated with immunohistochemical staining.The mRNAs and proteins associated with liver fibrosis were evaluated using RTQ-PCR and Western blot,respectively.Results: The mean fibrosis score of BDL rats treated with telmisartan was significantly lower than that of the model rats (1.66±0.87 vs 2.13±0.35,P=0.015).However,there was no significant difference in inflammation between the two groups,both of which showed moderate inflammation.Histologically,treatment with telmisartan significantly ameliorated BDL-caused the hepatic fibrosis.Treatment with telmisartan significantly upregulated the mRNA levels of ACE2 and MAS,and decreased the mRNA levels of ACE,angiotensin Ⅱ type 1 receptor (AT1-R),collagen type Ⅲ,and transforming growth factor β1 (TGF-β1).Moreover,treatment with telmisartan significantly increased the expression levels of ACE2 and MAS proteins,and inhibited the expression levels of ACE and AT1-R protein.Conclusion: Telmisartan attenuates liver fibrosis in bile duct-ligated rats via increasing ACE2 expression level.

  11. Infection with hepatitis A, B, C, and delta viruses among patients with acute hepatitis in Mongolia.

    Science.gov (United States)

    Tsatsralt-Od, Bira; Takahashi, Masaharu; Endo, Kazunori; Buyankhuu, Osorjin; Baatarkhuu, Oidov; Nishizawa, Tsutomu; Okamoto, Hiroaki

    2006-05-01

    One hundred ten consecutive patients (60 males and 50 females; age, mean +/- standard deviation [SD], 22.6 +/- 6.4 years; range 16-48 years) who were clinically diagnosed with sporadic acute hepatitis between December 2004 and January 2005 in Ulaanbaatar, Mongolia, were studied. IgM antibodies to hepatitis A virus were detected in 18 patients (16.4%), IgM antibodies to hepatitis B core (anti-HBc IgM) in 38 patients (34.5%) including two patients with concurrent hepatitis delta virus (HDV) infection, and hepatitis C virus RNA in nine patients (8.2%). There were 30 hepatitis B virus (HBV) carriers who had detectable hepatitis B surface antigen and antibodies to HDV but were negative for anti-HBc IgM, suggesting that they acquired type D acute hepatitis due to superinfection of HDV on a background of chronic HBV infection. None had IgM antibodies to hepatitis E virus (HEV). Consequently, 16.4, 32.7, 6.4, 1.8, and 27.3% of the patients were diagnosed as having acute hepatitis of type A, B, C, type B + D (HBV/HDV coinfection), and type D (superinfection of HDV), respectively. The cause of hepatitis was not known in the remaining 17 patients (15.5%). All 18 HAV isolates were genotyped as IA, all 9 HCV isolates were genotyped as 1b, and all 32 HDV isolates were classified into genotype I. The distribution of HBV genotypes among the 67 HBV isolates was A (1.5%, n = 1) and D (98.5%, n = 66). The present study indicates that de novo infections of HAV, HBV, HCV, and HDV are prevalent among young adults in Mongolia.

  12. Surgical attenuation of spontaneous congenital portosystemic shunts in dogs resolves hepatic encephalopathy but not hypermanganesemia.

    Science.gov (United States)

    Gow, Adam G; Frowde, Polly E; Elwood, Clive M; Burton, Carolyn A; Powell, Roger M; Tappin, Simon W; Foale, Rob D; Duncan, Andrew; Mellanby, Richard J

    2015-10-01

    Hypermanganesemia is commonly recognized in human patients with hepatic insufficiency and portosystemic shunting. Since manganese is neurotoxic, increases in brain manganese concentrations have been implicated in the development of hepatic encephalopathy although a direct causative role has yet to be demonstrated. Evaluate manganese concentrations in dogs with a naturally occurring congenital shunt before and after attenuation as well as longitudinally following the changes in hepatic encephalopathy grade. Our study demonstrated that attenuation of the shunt resolved encephalopathy, significantly reduced postprandial bile acids, yet a hypermanganasemic state persisted. This study demonstrates that resolution of hepatic encephalopathy can occur without the correction of hypermanganesemia, indicating that increased manganese concentrations alone do not play a causative role in encephalopathy. Our study further demonstrates the value of the canine congenital portosystemic shunt as a naturally occurring spontaneous model of human hepatic encephalopathy.

  13. Experience with lamivudine treatment for severe acute hepatitis B

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    Verhaz Antonija

    2014-01-01

    Full Text Available Introduction. Experience with lamivudine treatment for acute severe hepatitis B is limited. Fulminant hepatitis develops in 1% of immunocompetent patients with acute hepatitis B. Objective. The aim of this study was to evaluate the efficacy of lamivudine in the treatment of severe acute hepatitis B (SAHB in immunocompetent adult patients. Methods. Between January 2006 and May 2013 at the Clinic for Infectious Diseases Banja Luka, 13 patients with SAHB were treated with lamivudine at a dose of 100 mg per day. All 13 patients fulfilled at least two of three default criteria: 1. hepatic encephalopathy; 2. total bilirubin greater than 210 μmol/L; and 3. severe coagulopathy (international normalized ratio - INR ≥1.5 or prothrombin time - PT <40%. The criteria were defined according to the experiences reported in the study of Schmilovitz-Weiss et al. ”Lamivudine treatment for severe acute hepatitis B“. Nine patients had a rapid rise in the total bilirubin and decrease of alanine aminotransferase level, which escalated risk for development of fulminant hepatitis. Results. Within 1-6 months, HBsAg was undetectable in 12 of 13 examined patients. Protective anti-HBsAg developed in 10 of them during 2-14 months. Two patients did not develop protective antibodies, but the result of the analysis of PCR HBV DNA was repeatedly negative. Corticosteroids were shortly used in two patients. One patient died four days after starting the therapy. Lamivudine treatment was well tolerated by all patients. Conclusion. Early treatment with lamivudine can reduce the risk of progression to fulminant hepatitis in patients with SAHB.

  14. Acute hepatitis B or exacerbation of chronic hepatitis B-that is the question

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Hepatitis B virus (HBV) infection constitutes a serious global health problem. In countries with intermediate or high endemicity for HBV, exacerbations of chronic hepatitis B may be the first presentation of HBV infection. Some of these patients may be diagnosed mistakenly as having acute hepatitis B. Accurate diagnosis in these cases is very important for deciding whether to start treatment or not, because acute hepatitis B does not require therapy, while exacerbation of chronic hepatitis may benefit from it. Clinical and routine laboratory findings cannot help distinguishing between these two conditions. Therefore, several assays have been proposed for this purpose during the last few years. The presence of high levels of anti-HBe antibodies, HBsAg and HBV DNA are typical of chronic disease, whereas high titers of IgM anti-HBc, together with their high avidity index, characterize acute HBV infection. StarLing from the description of a patient with acute hepatitis B-who recently came to our observation-we critically review the currentlyavailable assays that may help distinguishing between the different conditions and lead to the optimal management of each patient.

  15. the Pathogenesis of acute on Chronic Hepatitis B liver Failure

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    Acute-on-chronic liver failure is a characteristic clinical liver syndrome, which should be differentiated from acute liver failure, acute decompensated liver cirrhosis and chronic liver failure. The pathogenesis of ACLF is not fully understood yet. Viral factors and immune injury have been reported to be the two major pathogenesis. This paper reviewed the researches on the pathogenesis of acute on chronic hepatitis B liver failure in recent years, to provide theoretical basis for prompt and accurate diagnosis and treatment of this syndrome. This would beneift for the prognosis and raise the survival rate of patients.

  16. Acute Liver Failure and Hepatic Encephalopathy After Cleft Palate Repair.

    Science.gov (United States)

    Kocaaslan, Nihal Durmuş; Tuncer, Fatma Betul; Tutar, Engin; Celebiler, Ozhan

    2015-09-01

    Paracetamol is the most commonly used analgesic after cleft palate repair. It has rarely caused acute hepatic failure at therapeutic or supratherapeutic doses. Only one case of therapeutic paracetamol toxicity after cleft palate repair had been reported previously. Here, we present a similar patient who developed acute liver failure and hepatic encephalopathy after an uncomplicated cleft palate surgery. Lack of large prospective trials in young children due to ethical concerns increases the value of the case reports of acetaminophen toxicity at therapeutic doses. The dosing recommendations of paracetamol may need to be reconsidered after cleft palate surgery.

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

    Science.gov (United States)

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

    2013-01-01

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

  18. [Hepatitis non-A, non-B: epidemiological significance in acute viral hepatitis and chronic active hepatitis of hepatological consultation].

    Science.gov (United States)

    Jmelnitzky, A C; Basualdo, J A; Belloni, P O; Ponce de León, H H; García, C; Curciarello, J

    1987-01-01

    157 acute viral hepatitis and 60 chronic active ones have been analyzed focusing on NANB etiology. HAV was implicated in 36.3% of the hole acute viral hepatitis sample, HBV in 29.3%, and HNANBV was presumed as etiology in 31.2%, 5 patients (3.2%) had acute infection by HAV, on previous one by HBV, except for Epstein-Barr virus, no other test for viruses were determined (CMV, HSV, etc.). Male/female ratio was 1.4:1, 1.9:1, and 1.4:1 for HAV, HBV and HNANBV acute hepatitis respectively; HAV was the main etiology in the 0-9 age group (72.2%) although it only represents 11.5% of the sample; small occurrence of HAV hepatitis were found in patients over 40 (8.8%); HBV was clearly prevalent in patients over 50 (65.2%); the highest concentration of NANB etiology was found between 20-39 years old, but it was represented in all age-groups. Out of 49 NANB acute hepatitis, 12.2% had related transfusional antecedents, 12.2% belonged to health care worker group, and 4.1% had a close family NANB hepatitis contact; 71.5% had no reported antecedent. Viral source was presumably implicated in 75.0% of chronic active hepatitis, 25.0% attributable to HNANBV. Results seem not feasible to transfer to general population due to the facts that most patients were of specialized consult, and pediatric assistance is unusual to the authors practice.

  19. Liver function tests in acute hepatitis in children

    Directory of Open Access Journals (Sweden)

    Shweta

    2016-08-01

    Conclusions: This study helps us to analyze the incidence of HBsAg positive cases presenting with clinical features of acute hepatitis and degree of alteration of liver functions would help the physician in better management of the cases. [Int J Res Med Sci 2016; 4(8.000: 3184-3187

  20. [Hepatic retransplant and acute Budd Chiari syndrome. Case report].

    Science.gov (United States)

    Savio-López, Andrés M; Lara-Molina, Evelin E; Soliva-Domínguez, Ramón; Capo-Jorge, José A; Gala-López, Boris; González-Castillo, Fernando

    2005-01-01

    Hepatic retransplant constitutes 10-20% of all orthotopic hepatic transplants. The piggy-back technique was used in hepatectomy with conservation of the retrohepatic vena cava. A side-to-side cavo-cavostomy technique is described in the case of hepatic congestion or acute Budd Chiari syndrome post-transplant. This is an extremely serious condition and can result in death. We present the first case of hepatic retransplant performed in Hospital Hermanos Ameijeiras in a patient who received who received his first transplant due to non-resectable hepatocarcinoma and who required retransplant due to acute rejection and graft dysfunction. During retransplant, the Belghiti side-to-side anastomosis technique was used to resolve the acute Budd Chiari syndrome that presented itself. Post-surgical evolution at 18 months was satisfactory without evidence of complications of the graft. Acute Budd Chiari syndrome post-transplant can satisfactorily be resolved with the Belghiti technique, although it is preferable to take prophylactic measures to avoid it.

  1. Sonographic changes of liver and gallbladder in acute viral hepatitis

    Directory of Open Access Journals (Sweden)

    Ebrahimi Daryani N

    2001-07-01

    Full Text Available Hepatomegaly, decrease in the liver paranchymal echo and increase in the gallbladder wall thickness has been shown in acute viral hepatitis. The present study was done to determine sonographic changes in acute viral hepatitis. We performed liver and bile ducts sonography and specific tests on 42 patients (mean age: 31.5 and 61% male with acute viral hepatitis. Gallbladder wall thickness was seen in 45.2% and hepatomegaly in 33.3% of patients and liver paranchymal echo was decreased in 19.3%. Age, sex, type of hepatitis, cholecystitis like symptoms, aspartate aminotransfrase, alanine aminotransfrase, alkaline phosphatase and bilirubin did not significantly corralate with these changes. Only raised prothrombin time was strongly correlated to the thickening of the gallbladder and decrease in the liver paranchymal echo and cholesistic like symptoms we can postulate that thickening of the gallbladder and decrease in the liver paranchymal echo is not dependent on the severity and speed of the paranchymal necrosis (as considered with ALT and AST but they depend on the liver function disturbance (as considered with PT because the thickening of the gall bladder is present in 45% of the patients and 10% of the normal population have gallbladder stones, one should not perform the diagnosis of acute cholecystitis, only on the basis of sonographic report without attention to the clinical and laboratory data.

  2. Deferoxamine attenuates acute hydrocephalus after traumatic brain injury in rats.

    Science.gov (United States)

    Zhao, Jinbing; Chen, Zhi; Xi, Guohua; Keep, Richard F; Hua, Ya

    2014-10-01

    Acute post-traumatic ventricular dilation and hydrocephalus are relatively frequent consequences of traumatic brain injury (TBI). Several recent studies have indicated that high iron levels in brain may relate to hydrocephalus development after intracranial hemorrhage. However, the role of iron in the development of post-traumatic hydrocephalus is still unclear. This study was to determine whether or not iron has a role in hydrocephalus development after TBI. TBI was induced by lateral fluid-percussion in male Sprague-Dawley rats. Some rats had intraventricular injection of iron. Acute hydrocephalus was measured by magnetic resonance T2-weighted imaging and brain hemorrhage was determined by T2* gradient-echo sequence imaging and brain hemoglobin levels. The effect of deferoxamine on TBI-induced hydrocephalus was examined. TBI resulted in acute hydrocephalus at 24 h (lateral ventricle volume: 24.1 ± 3.0 vs. 9.9 ± 0.2 mm(3) in sham group). Intraventricular injection of iron also caused hydrocephalus (25.7 ± 3.4 vs. 9.0 ± 0.6 mm(3) in saline group). Deferoxamine treatment attenuated TBI-induced hydrocephalus and heme oxygenase-1 upregulation. In conclusion, iron may contribute to acute hydrocephalus after TBI.

  3. [Consistency analysis on acute hepatitis B inpatients reported by hepatitis B surveillance pilot spots in six provinces of China].

    Science.gov (United States)

    Miao, N; Zhang, G M; Wang, F Z; Zheng, H; Sun, X J; Ma, X J; Cui, F Q

    2017-02-10

    Objective: To understand the characteristics of acute hepatitis B inpatients reported by the hepatitis B surveillance pilot points and to estimate the consistency between the diagnosed and reported types of hepatitis B by the clinicians involved. Methods: Data related to acute hepatitis B was from the NNDRS and the characteristics of acute hepatitis B were classified by querying Hospital Information System. We recorded the results based on clinical diagnosis and analyzed the consistency between the reported and diagnosed types that the clinicians made, on hepatitis B. Results: A total of 179 patients were included in this study with all of them as acute hepatitis B reported through NNDRS in 2015-2016. In terms of the durations of disease, among the 179 cases who were HBsAg positive, 32.40% (58/179) of them exceeding 6 months, 2.79% (5/179) within 6 months and 64.80% (116/179) tested the first time or never. Among the 179 cases who claimed having the history of hepatitis, 33.52% (60/179) of them identified as having hepatitis B, 1.12% (2/179) were hepatitis A, C or E, 41.34% (74/179) did not have the signs on hepatitis, while the rest 24.02% (43/179) did not know the situation. Only 79.89% (143/179) of the patients showed the symptoms or signs of hepatitis, but the rest 20.11% (36/179) did not. Among the 179 reported acute hepatitis patients, 67 of them were diagnosed as acute hepatitis B while 112 cases were as non-acute hepatitis B. The consistent rate of acute hepatitis B was 37.43% (67/179). Among the 112 cases that were diagnosed as non-acute hepatitis B, proportions of chronic hepatitis B and cirrhosis were 49.11%(55/112) and 16.07%(18/112) respectively. Conclusion: Consistency between the reported type of acute hepatitis B inpatients and the types diagnosed by clinicians was poor. Our results suggested that clinicians should make the accurate diagnosis at first place and then report to the Network in accordance with the clinical diagnosis classification

  4. Hydrogen sulfide protects against cognitive impairment induced by hepatic ischemia and reperfusion via attenuating neuroinflammation.

    Science.gov (United States)

    Tu, Faping; Li, Jingdong; Wang, Ji; Li, Qiang; Chu, Weihua

    2016-03-01

    Previously, hepatic ischemia followed by reperfusion (hepatic I/R) has been found to cause cognitive impairment. Hydrogen sulfide (H2S) attenuates hepatectomy induced cognitive deficits and also protects against cognitive dysfunction induced by neurodegenerative diseases. In this study, we aim to determine whether sodium hydrosulfide (NaHS), a H2S donor, could alleviate hepatic I/R-induced cognitive impairment and the underlying mechanisms. Rats were injected intraperitoneally with NaHS (5 mg/kg/d) for 11 days. A segmental hepatic I/R model was established on the fourth day. Cognitive function, proinflammatory cytokines levels, and hippocampal ionized calcium-binding adaptor molecule 1 (Iba1) expression was analyzed. We found hepatic I/R increased proinflammatory cytokines levels in serum and hippocampus, up-regulated Iba1 expression, leading to cognitive impairment in rats. However, treatment with NaHS alleviated hepatic I/R induced these neuroinflammatory changes and effectively improved cognitive function. Thus, NaHS appears to protect against cognitive impairment in rats undergoing hepatic I/R by attenuating neuroinflammation in the hippocampus.

  5. Acute Hepatic Failure in a Dog after Xylitol Ingestion.

    Science.gov (United States)

    Schmid, Renee D; Hovda, Lynn R

    2016-06-01

    Xylitol is a five-carbon sugar alcohol produced from natural resources frequently used as a sugar substitute for humans. We report the development and successful treatment of acute hepatic failure and coagulopathy in a dog after xylitol ingestion. A 9-year-old 4.95 kg (10.9 lb) neutered male Chihuahua was evaluated at a veterinary clinic for vomiting after ingesting 224 g (45 g/kg, 20.5 g/lb) of granulated xylitol. Hypoglycemia developed within 1-2 h, elevated liver values, suggesting the development of acute hepatic failure, within 12 h and coagulopathy less than 24 h after ingestion. Treatment included maropitant, intravenous dextrose, phytonadione, metronidazole, and fresh frozen plasma. N-acetylcysteine (NAC) and S-adensoyl-L-methionine (SAMe) provided hepatic detoxification and support. The dog survived and liver values returned to normal within 1 month post ingestion. No adverse effects to hepatic function have been identified 2 years after acute xylitol toxicity. This paper is one of the few reports of successful management of a dog with hypoglycemia, hepatic failure, and coagulopathy caused by xylitol toxicity. To date, this is the highest published xylitol dose survived by a dog, as well as the only reported case that documents laboratory changes throughout the course of toxicity and includes normal hepatic indices for 7 months following xylitol toxicity. The rapidly expanding use of xylitol in a variety of products intended for human consumption has led to a rise in xylitol toxicity cases reported in dogs, and clinicians should be aware that more dogs may potentially be exposed and develop similar manifestations.

  6. Combined antiretroviral therapy attenuates hepatic extracellular matrix remodeling in HIV patients assessed by novel protein fingerprint markers

    DEFF Research Database (Denmark)

    Leeming, Diana J; Anadol, Evrim; Schierwagen, Robert

    2014-01-01

    OBJECTIVES: Combined antiretroviral therapy (cART) attenuates hepatic fibrosis in hepatitis C virus and HIV coinfected patients. However, the role of HIV or cART on hepatic fibrosis in HIV monoinfection is discussed controversially. During liver fibrosis, matrix metalloproteinases (MMPs) degrade ...

  7. Atg7 Knockdown Augments Concanavalin A-Induced Acute Hepatitis through an ROS-Mediated p38/MAPK Pathway.

    Directory of Open Access Journals (Sweden)

    Yan Zhuang

    Full Text Available Concanavalin A (ConA, a T-cell mitogen that induces acute autoimmune hepatitis, is widely used to model pathophysiological processes of human acute autoimmune liver disease. Although autophagy has been extensively studied in the past decade, little is known about its molecular mechanism underlying the regulation of ConA-induced acute hepatitis. In this study, we used a Cre-conditional atg7 KO mouse to investigate the effects of Atg7-associated autophagy on ConA-induced murine hepatitis. Our results demonstrated that atg7 deficiency in mice enhanced macrophage activation and increased pro-inflammatory cytokines upon ConA stimulation. Atg7 silencing resulted in accumulation of dysfunctional mitochondria, disruption of reactive oxygen species (ROS degradation, and increase in pro-inflammatory cytokines in Raw264.7 cells. p38/MAPK and NF-κB levels were increased upon ConA induction due to Atg7 deficiency. Blocking ROS production inhibited ConA-induced p38/IκB phosphorylation and subsequent intracellular inflammatory responses. Hence, this study demonstrated that atg7 knockout in mice or Atg7 knockdown in cell culture augmented ConA-induced acute hepatitis and related cellular malfunction, indicating protective effects of Atg7 on regulating mitochondrial ROS via a p38/MAPK-mediated pathway. Collectively, our findings reveal that autophagy may attenuate macrophage-mediated inflammatory response to ConA and may be the potential therapeutic targets for acute liver injury.

  8. Butachlor-induced acute toxic hepatitis.

    Science.gov (United States)

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

    2007-01-01

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

  9. Tangeretin Alleviates Cisplatin-Induced Acute Hepatic Injury in Rats: Targeting MAPKs and Apoptosis.

    Science.gov (United States)

    Omar, Hany A; Mohamed, Wafaa R; Arab, Hany H; Arafa, El-Shaimaa A

    2016-01-01

    Despite its broad applications, cisplatin affords considerable nephro- and hepatotoxicity through triggering inflammatory and oxidative stress cascades. The aim of the current investigation was to study the possible protective effects of tangeretin on cisplatin-induced hepatotoxicity. The impact of tangeretin on cisplatin-evoked hepatic dysfunction and histopathologic changes along with oxidative stress, inflammatory and apoptotic biomarkers were investigated compared to silymarin. Tangeretin pre-treatment significantly improved liver function tests (ALT and AST), inhibited cisplatin-induced lipid profile aberrations (total cholesterol and triglycerides) and diminished histopathologic structural damage in liver tissues. Tangeretin also attenuated cisplatin-induced hepatic inflammatory events as indicated by suppression of tumor necrosis factor-α (TNF-α) and enhancement of interleukin-10 (IL-10). Meanwhile, it lowered malondialdehyde (MDA), nitric oxide (NO) and nuclear factor erythroid 2-related factor 2 (NRF-2) levels with restoration of glutathione (GSH), and glutathione peroxidase (GPx). Regarding mitogen-activated protein kinase (MAPK) pathway, tangeretin attenuated cisplatin-induced increase in phospho-p38, phospho-c-Jun N-terminal kinase (p-JNK) and phospho-extracellular signal-regulated kinase (p-ERK1/2) in liver tissues. In addition, tangeretin downregulated Bax expression with augmentation of Bcl-2 promoting liver cell survival. Our results highlight the protective effects of tangeretin against cisplatin-induced acute hepatic injury via the concerted modulation of inflammation, oxidative stress, MAPKs and apoptotic pathways.

  10. Tangeretin Alleviates Cisplatin-Induced Acute Hepatic Injury in Rats: Targeting MAPKs and Apoptosis.

    Directory of Open Access Journals (Sweden)

    Hany A Omar

    Full Text Available Despite its broad applications, cisplatin affords considerable nephro- and hepatotoxicity through triggering inflammatory and oxidative stress cascades. The aim of the current investigation was to study the possible protective effects of tangeretin on cisplatin-induced hepatotoxicity. The impact of tangeretin on cisplatin-evoked hepatic dysfunction and histopathologic changes along with oxidative stress, inflammatory and apoptotic biomarkers were investigated compared to silymarin. Tangeretin pre-treatment significantly improved liver function tests (ALT and AST, inhibited cisplatin-induced lipid profile aberrations (total cholesterol and triglycerides and diminished histopathologic structural damage in liver tissues. Tangeretin also attenuated cisplatin-induced hepatic inflammatory events as indicated by suppression of tumor necrosis factor-α (TNF-α and enhancement of interleukin-10 (IL-10. Meanwhile, it lowered malondialdehyde (MDA, nitric oxide (NO and nuclear factor erythroid 2-related factor 2 (NRF-2 levels with restoration of glutathione (GSH, and glutathione peroxidase (GPx. Regarding mitogen-activated protein kinase (MAPK pathway, tangeretin attenuated cisplatin-induced increase in phospho-p38, phospho-c-Jun N-terminal kinase (p-JNK and phospho-extracellular signal-regulated kinase (p-ERK1/2 in liver tissues. In addition, tangeretin downregulated Bax expression with augmentation of Bcl-2 promoting liver cell survival. Our results highlight the protective effects of tangeretin against cisplatin-induced acute hepatic injury via the concerted modulation of inflammation, oxidative stress, MAPKs and apoptotic pathways.

  11. Dengue hemorrhagic fever and acute hepatitis: a case report

    Directory of Open Access Journals (Sweden)

    Maria Paula Gomes Mourão

    2004-12-01

    Full Text Available Dengue fever is the world's most important viral hemorrhagic fever disease, the most geographically wide-spread of the arthropod-born viruses, and it causes a wide clinical spectrum of disease. We report a case of dengue hemorrhagic fever complicated by acute hepatitis. The initial picture of classical dengue fever was followed by painful liver enlargement, vomiting, hematemesis, epistaxis and diarrhea. Severe liver injury was detected by laboratory investigation, according to a syndromic surveillance protocol, expressed in a self-limiting pattern and the patient had a complete recovery. The serological tests for hepatitis and yellow fever viruses were negative. MAC-ELISA for dengue was positive.

  12. Acute exacerbation of autoimmune hepatitis induced by Twinrix

    Institute of Scientific and Technical Information of China (English)

    Antal Csepregi; Gerhard Treiber; Christoph R(o)cken; Peter Malfertheiner

    2005-01-01

    We report on a 26-year-old man who presented with severe jaundice and elevated serum liver enzyme activities after having received a dose of Twinrix(○R). In his past medical history, jaundice or abnormal liver function tests were never recorded. Following admission, an elevated immunoglobulin G level and antinuclear antibodies at a titer of 320 with a homogenous pattern were found. Histology of a liver biopsy showed marked bridging liver fibrosis and a chronic inflammation, compatible with autoimmune hepatitis. Treatment was started with budesonide and ursodeoxycholic acid,and led to complete normalization of the pathological liver function tests. We believe that Twinrix(○R) led to an acute exacerbation of an unrecognized autoimmune hepatitis in our patient. The pathogenesis remains to be clarified. It is tempting to speculate that inactivated hepatitis A virus and/or recombinant surface antigen of the hepatitis B virus -as seen in patients with chronic hepatitis C and unrecognized autoimmune hepatitis who were treated with interferon alpha-might have been responsible for disease exacerbation.

  13. Hepatitis E virus as a Cause of Acute Hepatitis in The Netherlands.

    Directory of Open Access Journals (Sweden)

    Aletta T R Tholen

    Full Text Available Recent studies indicate that 27% of Dutch blood donors have evidence of past infection with HEV. However, the low number of diagnosed HEV infections indicates either an asymptomatic course or under diagnosis.We investigated whether HEV is a cause of acute hepatitis in Dutch patients and which diagnostic modality (serology or PCR should be used for optimal detection.Serum samples were retrospectively selected from non-severely immuno-compromised patients from a university hospital population, suspected of having an infectious hepatitis. Criteria were: elevated alanine aminotransferase (ALT> 34 U/l and request for antibody testing for CMV, EBV or Hepatitis A (HAV.All samples were tested for HEV using ELISA and PCR. Ninety patients/sera were tested, of which 22% were HEV IgG positive. Only one serum was IgM positive. HEV PCR was positive in two patients: one patient was both HEV IgM and IgG positive, the other patient was only IgG positive. Both HEV RNA positive samples belonged to genotype 3. Evidence of recent infection with CMV, EBV and HAV was found in 13%, 10% and 3% respectively.Although our study is limited by small numbers, we conclude that HEV is a cause of acute hepatitis in hospital associated patients in The Netherlands. Moreover, in our study population the prevalence of acute HAV (3% was almost similar to acute HEV (2%. We propose to incorporate HEV testing in panels for acute infectious hepatitis. Negative results obtained for HEV IgM in a HEV PCR positive patient, indicates that antibody testing alone may not be sufficient and argues for PCR as a primary diagnostic tool in hospital associated patients. The high percentage of HEV IgG seropositivity confirms earlier epidemiological studies.

  14. Hepatic encephalopathy in acute-on-chronic liver failure.

    Science.gov (United States)

    Lee, Guan-Huei

    2015-10-01

    The presence of hepatic encephalopathy (HE) within 4 weeks is part of the criteria for defining acute-on-chronic liver failure (ACLF). The pathophysiology of HE is complex, and hyperammonemia and cerebral hemodynamic dysfunction appear to be central in the pathogenesis of encephalopathy. Recent data also suggest that inflammatory mediators may have a significant role in modulating the cerebral effect of ammonia. Multiple prospective and retrospective studies have shown that hepatic encephalopathy in ACLF patients is associated with higher mortality, especially in those with grade III-IV encephalopathy, similar to that of acute liver failure (ALF). Although significant cerebral edema detected by CT in ACLF patients appeared to be less common, specialized MRI imaging was able to detect cerebral edema even in low grade HE. Ammonia-focused therapy constitutes the basis of current therapy, as in the treatment of ALF. Emerging treatment strategies focusing on modulating the gut-liver-circulation-brain axis are discussed.

  15. Epigallocatechin-3-gallate attenuates apoptosis and autophagy in concanavalin A-induced hepatitis by inhibiting BNIP3

    Directory of Open Access Journals (Sweden)

    Li S

    2016-02-01

    Full Text Available Sainan Li, Yujing Xia, Kan Chen, Jingjing Li, Tong Liu, Fan Wang, Jie Lu, Yingqun Zhou, Chuanyong Guo Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China Background: Epigallocatechin-3-gallate (EGCG is the most effective compound in green tea, and possesses a wide range of beneficial effects, including anti-inflammatory, antioxidant, antiobesity, and anticancer effects. In this study, we investigated the protective effects of EGCG in concanavalin A (ConA-induced hepatitis in mice and explored the possible mechanisms involved in these effects.Methods: Balb/C mice were injected with ConA (25 mg/kg to induce acute autoimmune hepatitis, and EGCG (10 or 30 mg/kg was administered orally twice daily for 10 days before ConA injection. Serum liver enzymes, proinflammatory cytokines, and other marker proteins were determined 2, 8, and 24 hours after the ConA administration.Results: BNIP3 mediated cell apoptosis and autophagy in ConA-induced hepatitis. EGCG decreased the immunoreaction and pathological damage by reducing inflammatory factors, such as TNF-α, IL-6, IFN-γ, and IL-1β. EGCG also exhibited an antiapoptotic and antiautophagic effect by inhibiting BNIP3 via the IL-6/JAKs/STAT3 pathway.Conclusion: EGCG attenuated liver injury in ConA-induced hepatitis by downregulating IL-6/JAKs/STAT3/BNIP3-mediated apoptosis and autophagy. Keywords: concanavalin A, hepatitis, EGCG, autophagy, apoptosis, BNIP3, STAT3, JAKs, IL-6

  16. Arctigenin attenuates lipopolysaccharide-induced acute lung injury in rats.

    Science.gov (United States)

    Shi, Xianbao; Sun, Hongzhi; Zhou, Dun; Xi, Huanjiu; Shan, Lina

    2015-04-01

    Arctigenin (ATG) has been reported to possess anti-inflammatory properties. However, the effects of ATG on lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains not well understood. In the present study, our investigation was designed to reveal the effect of ATG on LPS-induced ALI in rats. We found that ATG pretreatment attenuated the LPS-induced ALI, as evidenced by the reduced histological scores, myeloperoxidase activity, and wet-to-dry weight ratio in the lung tissues. This was accompanied by the decreased levels of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-1 (IL-6) in the bronchoalveolar lavage fluid. Furthermore, ATG downregulated the expression of nuclear factor kappa B (NF-κB) p65, promoted the phosphorylation of inhibitor of nuclear factor-κB-α (IκBα) and activated the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPKα) in the lung tissues. Our results suggested that ATG attenuates the LPS-induced ALI via activation of AMPK and suppression of NF-κB signaling pathway.

  17. Desferrioxamine attenuates minor lung injury following surgical acute liver failure.

    Science.gov (United States)

    Kostopanagiotou, G G; Kalimeris, K A; Arkadopoulos, N P; Pafiti, A; Panagopoulos, D; Smyrniotis, V; Vlahakos, D; Routsi, C; Lekka, M E; Nakos, G

    2009-06-01

    Acute liver failure (ALF) can be complicated by lung dysfunction. The aim of this study was to test the hypothesis that inhibition of oxidative stress through iron chelation with desferrioxamine (DFX) attenuates pulmonary injury caused by ALF. 14 adult female domestic pigs were subjected to surgical devascularisation of the liver and were randomised to a study group (DFX group, n = 7), which received post-operative intravenous infusion of DFX (14.5 mg x kg(-1) x h(-1) for the first 6 h post-operatively and 2.4 mg x kg(-1) x h(-1) until completion of 24 h), and a control group (n = 7). Post-operative lung damage was evaluated by histological and bronchoalveolar lavage fluid (BALF) analysis. DFX resulted in reduced BALF protein levels and tissue phospholipase (PL)A(2) activity. Plasma malondialdehyde and BALF nitrate and nitrite concentrations were lower, while catalase activity in the lung was higher after DFX treatment. PLA(2), platelet-activating factor acetylhydrolase and total cell counts in BALF did not differ between groups. Histological examination revealed reduced alveolar collapse, pneumonocyte necrosis and total lung injury in the DFX-treated animals. DFX reduced systemic and pulmonary oxidative stress during ALF. The limited activity of PLA(2) and the attenuation of pneumonocyte necrosis could represent beneficial mechanisms by which DFX improves alveolar-capillary membrane permeability and prevents alveolar space collapse.

  18. Hepatitis A related acute liver failure by consumption of contaminated food.

    Science.gov (United States)

    Chi, Heng; Haagsma, Elizabeth B; Riezebos-Brilman, Annelies; van den Berg, Arie P; Metselaar, Herold J; de Knegt, Robert J

    2014-11-01

    We present a patient with no medical history admitted for jaundice and dark coloured urine. Further investigations revealed hepatitis A related acute liver failure while the patient had no travel history, nor contact with infected individuals. After admission, the patient deteriorated fulfilling the King's College criteria for acute liver failure. Two days after admission, he underwent liver transplantation and recovered. Careful investigation identified imported semi-dried tomatoes as the source of the hepatitis A infection. This patient was part of a foodborne hepatitis A outbreak in the Netherlands in 2010 affecting 13 patients. Virus sequence analysis of our patient's virus showed a strain commonly found in Turkey. Hepatitis A related acute liver failure is rare, but is associated with a poor prognosis. In developed countries, the incidence of hepatitis A is low, but foodborne outbreaks are emerging. Further, we review the literature on recent foodborne hepatitis A outbreaks in developed countries, hepatitis A related acute liver failure, and hepatitis A vaccine.

  19. Clinical epidemiology of acute hepatitis C in South America.

    Science.gov (United States)

    Dirchwolf, Melisa; Marciano, Sebastián; Mauro, Ezequiel; Ruf, Andrés Eduardo; Rezzonico, Lucrecia; Anders, Margarita; Chiodi, Daniela; Petta, Néstor Gill; Borzi, Silvia; Tanno, Federico; Ridruejo, Ezequiel; Barreyro, Fernando; Shulman, Carolina; Plaza, Pablo; Carbonetti, Rodolfo; Tadey, Luciana; Schroder, Teresa; Fainboim, Hugo

    2017-02-01

    There is scarce data pertaining to acute hepatitis C (aHC) infection in South America. We aimed to describe clinical characteristics and evolution of aHC in a South American cohort. A retrospective survey was conducted at 13 hepatology units. All patients ≥16 years old with aHC diagnosis were included. Demographic, clinical and outcome information were registered in a standardized ad hoc questionnaire. Sixty-four patients were included. The majority were middle-aged (median age: 46 years) and female (65.6%); most of them were symptomatic at diagnosis (79.6%). HCV-1 was the most prevalent genotype (69.2%). Five patients had liver failure: three cases of severe acute hepatitis, one case of fulminant hepatitis and one case of acute-on-chronic liver failure. Nosocomial exposure was the most prevalent risk factor. Evolution was assessed in 46 patients. In the untreated cohort, spontaneous resolution occurred in 45.8% and was associated with higher values of AST/ALT and with the absence of intermittent HCV RNA viremia (P = 0.01, 0.05, and 0.01, respectively). In the treated cohort, sustained virological response was associated with nosocomial transmission and early treatment initiation (P = 0.04 each). The prevalence of nosocomial transmission in this South-American cohort of aHC stresses the importance of following universal precautions to prevent HCV infection. J. Med. Virol. 89:276-283, 2017. © 2016 Wiley Periodicals, Inc.

  20. Immune thrombocytopenic purpura as sole manifestation in a case of acute hepatitis A.

    Science.gov (United States)

    Tanir, Gönül; Aydemir, Cumhur; Tuygun, Nilden; Kaya, Ozge; Yarali, Neşe

    2005-12-01

    Acute hepatitis due to hepatitis A virus is usually a benign selflimiting disease during childhood. Although many viral infections such as hepatitis B virus, Parvovirus, and Epstein-Barr virus are associated with extrahepatic autoimmune phenomena, such manifestations are rare in patients with acute hepatitis A infection. Immune thrombocytopenia is a benign, self-limiting disease in children, responding well to treatment and generally associated with viral infections. Immune thrombocytopenic purpura is rarely reported as a manifestation of acute hepatitis A. We report a five-year-old boy with immune thrombocytopenic purpura as the sole manifestation of anicteric acute hepatitis A infection. Acute hepatitis A should be included in the differential diagnosis of immune thrombocytopenic purpura.

  1. Protective effects of branched-chain amino acids on hepatic ischemia-reperfusion-induced liver injury in rats: a direct attenuation of Kupffer cell activation.

    Science.gov (United States)

    Kitagawa, Tomomi; Yokoyama, Yukihiro; Kokuryo, Toshio; Nagino, Masato

    2013-02-15

    We determined whether there is a protective effect of branched-chain amino acid (BCAA) on hepatic ischemia-reperfusion (I/R)-induced acute liver injury. Wister rats were divided into the following four groups: simple laparotomy with vehicle; simple laparotomy with BCAA (1 g/kg body wt orally); I/R (30 min clamp) with vehicle; and I/R with BCAA. Serum liver function tests and the gene expression of adhesion molecules (intercellular adhesion molecule and vascular cell adhesion molecule) and vasoconstrictor-related genes (endothelin-1) in the liver were examined. In the in vivo study, portal venous pressure, leukocyte adhesion, and hepatic microcirculation were evaluated. Furthermore, Kupffer cells were isolated and cultured with various concentrations of BCAA in the presence or absence of lipopolysaccharide (LPS). Increased levels of liver function tests following I/R were significantly attenuated by BCAA treatment. The increased expression of adhesion molecules and endothelin-1 was also significantly attenuated by BCAA treatment. Moreover, increased portal venous pressure, enhanced leukocyte adhesion, and deteriorated hepatic microcirculation following I/R were all improved by BCAA treatment. In the experiment using isolated Kupffer cells, the expression of interleukin-6, interleukin-1β, and endothelin-1 in response to LPS stimulation was attenuated by BCAA in a dose-dependent fashion. These results indicate that perioperative oral administration of BCAA has excellent therapeutic potential to reduce I/R-induced liver injury. These beneficial effects may result from the direct attenuation of Kupffer cell activation under stressful conditions.

  2. Parvovirus B19 in an Immunocompetent Adult Patient with Acute Liver Failure: An Underdiagnosed Cause of Acute Non-A-E Viral Hepatitis

    Directory of Open Access Journals (Sweden)

    J Kee Ho

    2005-01-01

    Full Text Available There are occasional pediatric reports of parvovirus B19-associated transient acute hepatitis and hepatic failure. A case of a 34-year-old immunocompetent woman who developed severe and prolonged but self-limited acute hepatitis and myelosuppression following acute parvovirus B19 infection is reported. Parvovirus B19 may be the causative agent in some adult cases of acute non-A-E viral hepatitis and acute liver failure.

  3. Curcumin attenuates diet-induced hepatic steatosis by activating AMP-activated protein kinase.

    Science.gov (United States)

    Um, Min Young; Hwang, Kwang Hyun; Ahn, Jiyun; Ha, Tae Youl

    2013-09-01

    Curcumin is a well-known component of traditional turmeric (Curcuma longa), which has been reported to prevent obesity and diabetes. However, the effect of curcumin on hepatic lipid metabolism remains unclear. The aim of this study was to examine the effects of curcumin on hepatic steatosis in high-fat/cholesterol diet (HFD)-induced obese mice. Male C57BL/6J mice were fed a normal diet (ND), HFD or HFD with 0.15% curcumin (HFD+C) for 11 weeks. We found that curcumin significantly lowered the body-weight and adipose tissue weight of mice in the HFD+C group compared with the findings for the HFD group (p cholesterol, fasting glucose and insulin in serum were decreased, and HFD-induced impairment of insulin sensitivity was improved by curcumin supplementation (p Curcumin protected against the development of hepatic steatosis by reducing hepatic fat accumulation. Moreover, curcumin activated AMP-activated protein kinase (AMPK) and elevated the gene expression of peroxisome proliferator-activated receptor alpha. By contrast, curcumin suppressed the HFD-mediated increases in sterol regulatory element-binding protein-1, acetyl-CoA carboxylase 1, fatty acid synthase and cluster of differentiation 36 expression. Taken together, these findings indicate that curcumin attenuates HFD-induced hepatic steatosis by regulating hepatic lipid metabolism via AMPK activation, suggesting its use as a therapeutic for hepatic steatosis.

  4. Attenuation of CCl4-induced hepatic fibrosis in mice by vaccinating against TGF-β1.

    Directory of Open Access Journals (Sweden)

    Xiaobao Fan

    Full Text Available Transforming growth factor β1 (TGF-β1 is the pivotal pro-fibrogenic cytokine in hepatic fibrosis. Reducing the over-produced expression of TGF-β1 or blocking its signaling pathways is considered to be a promising therapeutic strategy for hepatic fibrosis. In this study, we evaluated the feasibility of attenuating hepatic fibrosis by vaccination against TGF-β1 with TGF-β1 kinoids. Two TGF-β1 kinoid vaccines were prepared by cross-linking TGF-β1-derived polypeptides (TGF-β1(25-[41-65] and TGF-β1(30-[83-112] to keyhole limpet hemocyanin (KLH. Immunization with the two TGF-β1 kinoids efficiently elicited the production of high-levels of TGF-β1-specific antibodies against in BALB/c mice as tested by enzyme-linked immunosorbent assay (ELISA and Western blotting. The antisera neutralized TGF-β1-induced growth-inhibition on mink lung epithelial cells (Mv1Lu and attenuated TGF-β1-induced Smad2/3 phosphorylation, α-SMA, collagen type 1 alpha 2 (COL1A2, plasminogen activator inhibitor-1 (PAI-1 and tissue inhibitor of metalloproteinase-1 (TIMP-1 expression in the rat hepatic stellate cell (HSC line, HSC-T6. Vaccination against TGF-β1 with the kinoids significantly suppressed CCl4-induced collagen deposition and the expression of α-SMA and desmin, attenuated hepatocyte apoptosis and accelerated hepatocyte proliferation in BALB/c mice. These results demonstrated that immunization with the TGF-β1 kinoids efficiently attenuated CCl4-induced hepatic fibrosis and liver injury. Our study suggests that vaccination against TGF-β1 might be developed into a feasible therapeutic approach for the treatment of chronic fibrotic liver diseases.

  5. A homosexual japanese man with acute hepatitis due to hepatitis B virus genotype ae, concurrent with amebic colitis

    OpenAIRE

    Sakaguchi, Kohsaku; KOBASHI, HARUHIKO; Takaki,Akinobu; Kato, Jun; Nawa,Toru; Tatsukawa, Masashi; ISHIKAWA, SHIN; Iwasaki, Yoshiaki; Miyake,Yasuhiro; Shiratori, Yasushi

    2007-01-01

    We report herein a case with acute hepatitis due to hepatitis B virus genotype Ae, concurrent with amebic colitis. A 39-year-old homosexual Japanese man was admitted to our hospital with jaundice. Laboratory tests showed an elevation of transaminase and positivity for hepatitis B surface antigen and IgM-type antibody to hepatitis B core antigen. The hepatitis B virus genotype was determined to be Ae. Furthermore, a mud-like stool with blood and mucous had sometimes been noted during the past ...

  6. Integration of hepatitis B virus DNA into chromosomal DNA during acute hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Gerald C Kimbi; Anna Kramvis; Michael C Kew

    2005-01-01

    AIM: To examine the serum from black African patients with acute hepatitis B to ascertain if integrants of viral DNA can be detected in fragments of cellular DNA leaking from damaged hepatocytes into the circulation.METHODS: DNA was extracted from the sera of five patients with uncomplicated acute hepatitis B and one with fulminant disease. Two subgenomic PCRs designed to amplify the complete genome of HBV were used and the resulting amplicons were cloned and sequenced.RESULTS: HBV and chromosomal DNA were amplified from the sera of all the patients. In one patient with uncomplicated disease, HBV DNA was integrated into host chromosome 7 q11.23 in the WBSCR1 gene. The viral DNA comprised 200 nucleotides covering the S and X genes in opposite orientation, with a 1 169 nudeotide deletion. The right virus/host junction was situated at nucleotide 1774 in the cohesive overlap region of the viral genome, at a preferred topoisomerase I cleavage motif. The chromosomal DNA was not rearranged.The patient made a full recovery and seroconverted to anti-HBs- and anti-HBe-positivity. Neither HBV nor chromosomal DNA could be amplified from his serum at that time.CONCLUSION: Integration of viral DNA into chromosomal DNA may occur rarely during acute hepatitis B and, with clonal propagation of the integrant, might play a role in hepatocarcinogenesis.

  7. [Two cases of acute hepatitis associated with Q fever].

    Science.gov (United States)

    Yeşilyurt, Murat; Kılıç, Selçuk; Gürsoy, Bensu; Celebi, Bekir; Yerer, Mehmet

    2012-07-01

    Q fever which is caused by Coxiella burnetii, is a worldwide zoonosis. Many species of wild and domestic mammals, birds, and arthropods, are reservoirs of C.burnetii in nature, however farm animals are the most frequent sources of human infection. The most frequent way of transmission is by inhalation of contaminated aerosols. The clinical presentation of Q fever is polymorphic and nonspecific. Q fever may present as acute or chronic disease. In acute cases, the most common clinical syndromes are selflimited febrile illness, granulomatous hepatitis, and pneumonia, but it can also be asymptomatic. Fever with hepatitis associated with Q fever has rarely been described in the literature. Herein we report two cases of C.burnetii hepatitis presented with jaundice. In May 2011, two male cases, who inhabited in Malkara village of Tekirdag province (located at Trace region of Turkey), were admitted to the hospital with the complaints of persistent high grade fever, chills and sweats, icterus, disseminated myalgia and headache. Physical examination revealed fever, icterus and the patient appeared to be mildly ill but had no localizing signs of infection. Radiological findings of the patients were in normal limits. Laboratory findings revealed leukocytosis, increased hepatic and cholestatic enzyme levels, and moderate hyperbilirubinemia- mainly direct bilirubin, whereas serum C-reactive protein and erythrocyte sedimentation rate were found normal. Blood and urine cultures of the patients yielded no bacterial growth. Serological markers for acute viral hepatitis, citomegalovirus and Epstein-Barr virus infections, brucellosis, salmonellosis, toxoplasmosis and leptospirosis were found negative. Acute Q fever diagnosis of the cases were based on the positive results obtained by C.burnetii Phase II IgM and IgG ELISA (Vircell SL, Spain) test, and the serological diagnosis were confirmed by Phase I and II immunofluorescence (Vircell SL, Spain) method. Both cases were treated with

  8. Novel matrine derivative MD-1 attenuates hepatic fibrosis by inhibiting EGFR activation of hepatic stellate cells.

    Science.gov (United States)

    Feng, Yi; Ying, Hai-Yan; Qu, Ying; Cai, Xiao-Bo; Xu, Ming-Yi; Lu, Lun-Gen

    2016-09-01

    Matrine (MT), the effective component of Sophora flavescens Ait, has been shown to have anti-inflammation, immune-suppressive, anti-tumor, and anti-hepatic fibrosis activities. However, the pharmacological effects of MT still need to be strengthened due to its relatively low efficacy and short half-life. In the present study, we report a more effective thio derivative of MT, MD-1, and its inhibitory effects on the activation of hepatic stellate cells (HSCs) in both cell culture and animal models. Cytological experiments showed that MD-1 can inhibit the proliferation of HSC-T6 cells with a half-maximal inhibitory concentration (IC50) of 62 μmol/L. In addition, MD-1 more strongly inhibits the migration of HSC-T6 cells compared to MT and can more effectively induce G0/G1 arrest and apoptosis. Investigating the biological mechanisms underlying anti-hepatic fibrosis in the presence of MD-1, we found that MD-1 can bind the epidermal growth factor receptor (EGFR) on the surface of HSC-T6 cells, which can further inhibit the phosphorylation of EGFR and its downstream protein kinase B (Akt), resulting in decreased expression of cyclin D1 and eventual inhibition of the activation of HSC-T6 cells. Furthermore, in rats with dimethylnitrosamine (DMN)-induced hepatic fibrosis, MD-1 slowed the development and progression of hepatic fibrosis, protecting hepatic parenchymal cells and improving hepatic functions. Therefore, MD-1 is a potential drug for anti-hepatic fibrosis.

  9. CTRP3 attenuates diet-induced hepatic steatosis by regulating triglyceride metabolism

    Science.gov (United States)

    Peterson, Jonathan M.; Seldin, Marcus M.; Wei, Zhikui; Aja, Susan

    2013-01-01

    CTRP3 is a secreted plasma protein of the C1q family that helps regulate hepatic gluconeogenesis and is downregulated in a diet-induced obese state. However, the role of CTRP3 in regulating lipid metabolism has not been established. Here, we used a transgenic mouse model to address the potential function of CTRP3 in ameliorating high-fat diet-induced metabolic stress. Both transgenic and wild-type mice fed a high-fat diet showed similar body weight gain, food intake, and energy expenditure. Despite similar adiposity to wild-type mice upon diet-induced obesity (DIO), CTRP3 transgenic mice were strikingly resistant to the development of hepatic steatosis, had reduced serum TNF-α levels, and demonstrated a modest improvement in systemic insulin sensitivity. Additionally, reduced hepatic triglyceride levels were due to decreased expression of enzymes (GPAT, AGPAT, and DGAT) involved in triglyceride synthesis. Importantly, short-term daily administration of recombinant CTRP3 to DIO mice for 5 days was sufficient to improve the fatty liver phenotype, evident as reduced hepatic triglyceride content and expression of triglyceride synthesis genes. Consistent with a direct effect on liver cells, recombinant CTRP3 treatment reduced fatty acid synthesis and neutral lipid accumulation in cultured rat H4IIE hepatocytes. Together, these results establish a novel role for CTRP3 hormone in regulating hepatic lipid metabolism and highlight its protective function and therapeutic potential in attenuating hepatic steatosis. PMID:23744740

  10. Glutamine Attenuates Acute Lung Injury Caused by Acid Aspiration

    Directory of Open Access Journals (Sweden)

    Chih-Cheng Lai

    2014-08-01

    Full Text Available Inadequate ventilator settings may cause overwhelming inflammatory responses associated with ventilator-induced lung injury (VILI in patients with acute respiratory distress syndrome (ARDS. Here, we examined potential benefits of glutamine (GLN on a two-hit model for VILI after acid aspiration-induced lung injury in rats. Rats were intratracheally challenged with hydrochloric acid as a first hit to induce lung inflammation, then randomly received intravenous GLN or lactated Ringer’s solution (vehicle control thirty min before different ventilator strategies. Rats were then randomized to receive mechanical ventilation as a second hit with a high tidal volume (TV of 15 mL/kg and zero positive end-expiratory pressure (PEEP or a low TV of 6 mL/kg with PEEP of 5 cm H2O. We evaluated lung oxygenation, inflammation, mechanics, and histology. After ventilator use for 4 h, high TV resulted in greater lung injury physiologic and biologic indices. Compared with vehicle treated rats, GLN administration attenuated lung injury, with improved oxygenation and static compliance, and decreased respiratory elastance, lung edema, extended lung destruction (lung injury scores and lung histology, neutrophil recruitment in the lung, and cytokine production. Thus, GLN administration improved the physiologic and biologic profiles of this experimental model of VILI based on the two-hit theory.

  11. Thymoquinone Attenuates Diethylnitrosamine Induction of Hepatic Carcinogenesis Through Antioxidant Signaling

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    Mohamed M. Sayed-Ahmed

    2010-01-01

    Full Text Available Hepatocellular carcinoma accounts for about 80–90% of all liver cancer and is the fourth most common cause of cancer mortality. Although there are many strategies for the treatment of liver cancer, chemoprevention seems to be the best strategy for lowering the incidence of this disease. Therefore, this study has been initiated to investigate whether thymoquinone (TQ, Nigella sativa derived-compound with strong antioxidant properties, supplementation could prevent initiation of hepatocarcinogenesis-induced by diethylnitrosamine (DENA, a potent initiator and hepatocarcinogen, in rats. Male Wistar albino rats were divided into four groups. Rats of Group 1 received a single intraperitoneal (I.P. injection of normal saline. Animals in Group 2 were given TQ (4 mg/kg/day in drinking water for 7 consecutive days. Rats of Group 3 were injected with a single dose of DENA (200 mg/kg, I.P.. Animals in Group 4 were received TQ and DENA. DENA significantly increased alanine transaminase (ALT, alkaline phosphatase (ALP, total bilirubin, thiobarbituric acid reactive substances (TBARS and total nitrate/nitrite (NOx and decreased reduced glutathione (GSH, glutathione peroxidase (GSHPx, glutathione-s-transferase (GST and catalase (CAT activity in liver tissues. Moreover, DENA decreased gene expression of GSHPx, GST and CAT and caused severe histopathological lesions in liver tissue. Interestingly, TQ supplementation completely reversed the biochemical and histopathological changes induced by DENA to the control values. In conclusion, data from this study suggest that: (1 decreased mRNA expression of GSHPx, CAT and GST during DENA-induced initiation of hepatic carcinogenesis, (2 TQ supplementation prevents the development of DENA-induced initiation of liver cancer by decreasing oxidative stress and preserving both the activity and mRNA expression of antioxidant enzymes.

  12. Acute hypoxia and cytochrome P450-mediated hepatic drug metabolism in humans

    DEFF Research Database (Denmark)

    Jürgens, Gesche; Christensen, Hanne Rolighed; Brøsen, Kim;

    2002-01-01

    Our objective was to investigate the effect of acute hypoxia on the activity of hepatic cytochrome P450 (CYP) enzymes.......Our objective was to investigate the effect of acute hypoxia on the activity of hepatic cytochrome P450 (CYP) enzymes....

  13. Risk factors of acute hepatic failure during antituberculosis treatment: two cases and literature review

    NARCIS (Netherlands)

    Smink, F.; van Hoek, B.; Ringers, J.; van Altena, R.; Arend, S.M.

    2006-01-01

    Hepatotoxicity is a well-known side effect of antituberculosis treatment (ATT). If not recognised in time, drug-induced hepatitis can develop, which may rapidly progress to acute liver failure. We describe two patients with acute hepatic failure caused by ATT, whose pretreatment liver function had b

  14. Risk factors of acute hepatic failure during antituberculosis treatment : two cases and literature review

    NARCIS (Netherlands)

    Smink, F.; van Hoek, B.; Ringers, J.; van Altena, R.; Arend, S. M.

    2006-01-01

    Hepatotoxicity is a well-known side effect of antituberculosis treatment (ATT). If not recognised in time, drug-induced hepatitis can develop, which may rapidly progress to acute liver failure. We describe two patients with acute hepatic failure caused by ATT, whose pretreatment liver function had b

  15. Acute hepatitis in a patient using a Chinese herbal tea - a case report

    NARCIS (Netherlands)

    Levi, M; Guchelaar, HJ; Woerdenbag, HJ

    1998-01-01

    A case is presented of reversible acute hepatitis in a patient using a Chinese herbal tea. Upon identification of the tea mixture Aristolochia species, including A. debilis, which contains the highly toxic aristolochic acid, could be identified. We conclude that the acute hepatitis as described in t

  16. Petroselinum crispum extract attenuates hepatic steatosis in rats fed with fructose enriched diet.

    Science.gov (United States)

    Nair, V Yuneesha; Balakrishanan, N; Antony Santiago, J Victor

    2015-01-01

    Non alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and ongoing research efforts are focused on understanding the underlying pathophysiology of hepatic steatosis with the anticipation that these efforts will identify novel therapeutic targets. This study investigated the Petroselinum crispum extract in hepatic steatosis in rats fed with fructose enriched diet. Rats were divided into the 4 groups: Group 1 rats received standard pellet diet with corn starch for the entire experimental period of 8 weeks. Group 2 rats received standard pellet diet and 2 gm/kg body weight crude Parsley leaf ethanol extract for the entire experimental period of 8 weeks. Group 3 rats received modified fructose diet. Group 4 rats received modified fructose diet and 2gm/kg crude Parsley leaf ethanol extract. Hepatic function and structure was evaluated in these rats. Modified fructose diet produced dyslipidemia, hepatic steatosis and infiltration of inflammatory cells in the liver and higher plasma hepatic markers. Petroselinum crispum extract reversed metabolic changes such as abnormal crispum extract attenuated chronic changes in modified fructose diet induced NAFLD (Tab. 2, Fig. 3, Ref. 43).

  17. Jiao Tai Wan Attenuates Hepatic Lipid Accumulation in Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Zhaoyi Huang

    2013-01-01

    Full Text Available Jiao Tai Wan (JTW, a Chinese herbal formula containing Rhizoma Coptidis and Cortex Cinnamomi, has been used for diabetic treatment for many years. The aim of this study was to determine the main components in JTW and to investigate the effects of JTW on hepatic lipid accumulation in diabetic rats and humans. JTW extract was prepared and the main components were assayed by HPLC. An animal model of diabetes mellitus was established and JTW was administered intragastrically. In the clinical study, diabetic patients with poor glycemic control were treated with JTW. Blood glucose and lipid parameters, liver histology, hepatic triglyceride content and lipogenic gene expression were examined. Our data demonstrated that JTW significantly improved hyperglycemia, hyperlipidemia and hepatic lipid accumulation in diabetic rats. This was accompanied by the down-regulation of acetyl coenzyme A carboxylase (ACC and fatty acid synthase (FAS protein expressions, and the up-regulation of AMP-activated protein kinase (AMPK and phosphorylated-ACC (pACC protein expressions in the liver tissues. Diabetic patients also exhibited decreases in their hepatic triglyceride content. The results suggest that JTW attenuates hepatic lipid accumulation in diabetic rats and humans. These beneficial effects are possibly associated with the inhibition of lipogenic gene expression in the liver.

  18. Acute hepatitis with observed increased blood phenytoin level:a case study

    Institute of Scientific and Technical Information of China (English)

    Beuy Joob; Viroj Wiwanitkit

    2014-01-01

    Acute hepatitis is a common problem in medical practice.This problem can be fatal if there is no proper management.For management, the investigation for the cause is necessary.In the case report, the authors present an interesting male case presenting with unexplained acute hepatitis.The routine laboratory investigation cannot reveal the cause of hepatitis.The additional toxicological drug test can reveal the unexplained increased level of phenytoin.

  19. Chronic Hepatitis B with Spontaneous Severe Acute Exacerbation

    Directory of Open Access Journals (Sweden)

    Wei-Lun Tsai

    2015-11-01

    Full Text Available Chronic hepatitis B virus (HBV infection is a major global health problem with an estimated 400 million HBV carriers worldwide. In the natural history of chronic hepatitis B (CHB, spontaneous acute exacerbation (AE is not uncommon, with a cumulative incidence of 10%–30% every year. While exacerbations can be mild, some patients may develop hepatic decompensation and even die. The underlying pathogenesis is possibly related to the activation of cytotoxic T lymphocyte-mediated immune response against HBV. An upsurge of serum HBV DNA usually precedes the rise of alanine aminotransferase (ALT and bilirubin. Whether antiviral treatment can benefit CHB with severe AE remains controversial, but early nucleos(tide analogues treatment seemed to be associated with an improved outcome. There has been no randomized study that compared the effects of different nucleos(tide analogues (NA in the setting of CHB with severe AE. However, potent NAs with good resistance profiles are recommended. In this review, we summarized current knowledge regarding the natural history, pathogenetic mechanisms, and therapeutic options of CHB with severe AE.

  20. [Acute hepatitis in a patient with adult onset Still disease].

    Science.gov (United States)

    Gallo, M; Calvanese, A; Oscuro, F; Gallo, A; Caso, P; Annibale, E; Farinato, N

    1997-04-01

    Liver abnormalities in the course of Adult Onset Still's Disease (AOSD), both in form of hepatomegaly and elevation of hepatic enzymes, have been reported in up to three-quarts of the affected patients. These abnormalities may reflect disease activity or may be induced by drugs. Only in a few of this patients a liver biopsy was performed. However liver histology has shown, generally, non specific abnormalities or even normal pictures. We have recently observed a 47-year-old woman with a febrile illness started five months before, who after pertinent investigation was diagnosed as AOSD (according to criteria of Yamaguchi et al.). Apart from laboratory findings characteristic of an inflammatory disease, in absence of drug therapies the biochemical data showed raised levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and aminoglutamil transferase. Serological tests for either viral hepatitis viruses (HAV, HBV, HCV) or other viruses were negative. Ultrasonographic examination of gallbladder and bile ducts did not find gallstones or other abnormalities. A liver biopsy was performed, which histopathologic examination showed moderate fatty methamorphosis with focal areas of hepatocellular swelling with minimal necrosis, mild Kuppfer cell hyperplasia, portal and sinusoidal infiltrates of mononuclear cells. This picture consisted with the diagnosis of an acute unspecific reactive hepatitis.

  1. Hepatic artery pseudoaneurysm caused by acute idiopathic pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Yeon Hwa Yu; Joo Hyun Sohn; Tae Yeob Kim; Jae Yoon Jeong; Dong Soo Han; Yong Cheol Jeon; Min Young Kim

    2012-01-01

    Hepatic artery pseudoaneurysm (HAP) is a very rare disease but in cases of complication,there is a very high mortality.The most common cause of HAP is iatrogenic trauma such as liver biopsy,transhepatic biliary drainage,cholecystectomy and hepatectomy.HAP may also occur with complications such as infections or inflammation associated with septic emboli.HAP has been reported rarely in patients with acute pancreatitis.As far as we are aware,there is no report of a case caused by acute idiopathic pancreatitis,particularly.We report a case of HAP caused by acute idiopathic pancreatitis which developed in a 61-year-old woman.The woman initially presented with acute pancreatitis due to unknown cause.After conservative management,her symptoms seemed to have improved.But eight days after admission,abdominal pain abruptly became worse again.Abdominal computed tomography (CT) was rechecked and it detected a new HAP that was not seen in a previous abdominal CT.Endoscopic retrograde cholangiopancreatography (ERCP) was performed because of a suspicion of hemobilia as a cause of aggravated abdominal pain.ERCP confirmed hemobilia by observing fresh blood clots at the opening of the ampulla and several filling defects in the distal common bile duct on cholangiogram.Without any particular treatment such as embolization or surgical ligation,HAP thrombosed spontaneously.Three months after discharge,abdominal CT demonstrated that HAP in the left lateral segment had disappeared.

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

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

    Science.gov (United States)

    Kryczka, Wiesław; Walewska-Zielecka, Bozena; Dutkiewicz, Ewa

    2003-08-01

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

  4. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005226 Characteristics of peripheral blood T lymphocyte subsets in hepatitis B patients. FAN Zhen-ping(范振平),et al. Center Bio Ther, Instit Infect Dis, 302 Hosp Chin PLA, Beijing 100039. World Chin J Digestol, 2005;13(2): 194-197. Objective: To characterize the T-lymphocyte subsets in peripheral blood of patients with acute and chronic hepatitis B, and to explore their relations with the disease state. Methods: Peripheral blood

  5. Transient hepatic attenuation difference (THAD) in patients without neoplasm. Frequency, shape, distribution, and causes

    Energy Technology Data Exchange (ETDEWEB)

    Yamasaki, Michio; Furukawa, Akira; Murata, Kiyoshi; Morita, Rikushi [Shiga Univ. of Medical Science, Otsu (Japan)

    1999-03-01

    Transient hepatic attenuation difference (THAD) is a valuable finding in detecting hypervascular lesions. However, similar findings are also observed in patients even without known hepatic diseases. We elucidate the characteristic findings and the causes of THAD in patients without hepatic neoplasm in this article. Dual-phased contrast-enhanced CT studies performed in 450 patients were reviewed, and THAD was observed in 42 (9.3%). THAD was linear or wedge-shaped and was seen contiguous to the liver surface with a relatively obscure margin in 40 of the 42 cases. The most common cause of THAD was chronic cholecystitis followed by previous biliary surgery. THAD was also seen in 30 patients with no hepatic diseases in whom it had a tendency to locate around the gallbladder fossa or in the periphery of the liver particularly in the left lobe. The knowledge of the prevalence, shape, distribution and causes of THAD is essential for the evaluation of contrast-enhanced CT images obtained during the arterial phase. (author)

  6. Genistein Attenuates Nonalcoholic Steatohepatitis and Increases Hepatic PPARγ in a Rat Model

    Directory of Open Access Journals (Sweden)

    Warinda Susutlertpanya

    2015-01-01

    Full Text Available Nonalcoholic steatohepatitis (NASH has become a global chronic liver disease, but no effective medicine has been proven to cure it. This study investigated the protective effects of genistein, a phytoestrogen, on NASH and examined whether it has any effect on hepatic PPARγ. Male Sprague-Dawley rats were divided into four groups: control group fed ad libitum with standard rat diet, NASH group fed ad libitum with high-fat diet to induce NASH and NASH + Gen8 group and NASH + Gen16 group fed with high-fat diet plus intragastric administration of 8 or 16 mg/kg genistein once daily. After 6 weeks, liver samples were collected to determine MDA, TNF-α, PPARγ, and histopathology. The findings were that levels of hepatic MDA and TNF-α increased in NASH group, but 16 mg/kg genistein reduced these levels significantly. Downregulation of hepatic PPARγ was observed in NASH group, but genistein significantly upregulated the expression of PPARγ in both NASH + Gen groups. The histological appearance of liver in NASH group presented pathological features of steatohepatitis which were diminished in both NASH + Gen groups. The results suggest that genistein attenuates the liver histopathology of NASH with upregulation of hepatic PPARγ, reduction of oxidative stress, and inhibition of inflammatory cytokine.

  7. Effect of gomisin A in an immunologically-induced acute hepatic failure model.

    Science.gov (United States)

    Mizoguchi, Y; Shin, T; Kobayashi, K; Morisawa, S

    1991-02-01

    Guinea pigs were sensitized with trinitrophenylated liver macromolecular protein fraction (TNP-LP1) prepared by using sodium trinitrobenzenesulfonate of strong immunogenicity as the hapten and LP1 as the carrier protein. The administration of trinitrophenylated hepatocytes and lipopolysaccharide to these TNP-LP1-sensitized guinea pigs through the mesenteric vein 2 weeks later resulted in the induction of acute hepatic failure accompanied by massive hepatic cell necrosis in almost all of the guinea pigs. Using this experimental model, the effect of Gomisin A on the induction of immunological acute hepatic failure was examined. As a result, the administration of gomisin A remarkably improved the survival rate and serum transaminase levels of the immunologically-induced acute hepatic failure guinea pigs. Gomisin A also improved the histological changes of the liver in these guinea pigs. These results suggested that gomisin A is effective for the improvement of immunologically-induced acute hepatic failure in our experimental model.

  8. Persistent efficacy of live attenuated hepatitis A vaccine (H2-strain) after a mass vaccination program

    Institute of Scientific and Technical Information of China (English)

    ZHUANG Fang-cheng; QIAN Wen; MAO Zi-an; GONG Yue-ping; JIANG Qi; JIANG Li-min; CHEN Nian-liang; CHAI Shao-ai; MAO Jiang-sen

    2005-01-01

    Background Live attenuated hepatitis A vaccine (H2 strain) is widely applied in prevention of hepatitis A epidemic in China and other countries now. It is essential to observe and confirm the vaccine immune efficacy, population antibody level and its persistent efficacy after mass immunization.Methods A total of 220 children with negative anti-HAV antibody (aged 1-3 years) were taken for follow-up assay to observe seroconversion and geometric mean titre(GMT)level 2 months, 12 months, 6 years, and 10 years after inoculation. Another survey sampled from subjects of different age groups (3, 6, 9, 15, 18, 25 and 35 years) to compare anti-HA antibody positive rate before and after inoculation performed 10 years previously. Epidemiological observations were taken for 10 years to evaluate the relationship between vaccine coverage and hepatitis A morbidity. Serum antibody to HAV was detected by enzyme linked immunoassay (ELISA, calibrated by WHO international reference) and ABBOTT Axsym HAVAB microparticle enzyme immunoassay. Results Seroconversion in follow-up assay 2 months and 10 years after inoculation was 98.6% and 80.2% respectively. For children, the vaccination anti-HA antibody positive rates were significantly different before and after 10 years, 7.69% cf 70.45% (aged 3 years) and 52.58% cf 71.78% (aged 18 years). When vaccine coverage rose from 57% to 74%, there were no any HA epidemics. When vaccine coverage reached 85%, there were no any HA cases. With vaccine coverage between 85% and 91%, there were no any HA cases in cohorts from the age of 1 year to 15 years during the 10 years. Conclusions Live attenuated hepatitis A vaccine has an obvious long-term effectiveness in prevention and control of HA epidemics through mass vaccination.

  9. Prevalence of hepatitis viruses in patients with acute hepatitis and characterization of the detected genotype 4 hepatitis E virus sequences in Mongolia.

    Science.gov (United States)

    Tsatsralt-Od, Bira; Baasanjav, Nachin; Nyamkhuu, Dulmaa; Ohnishi, Hiroshi; Takahashi, Masaharu; Okamoto, Hiroaki

    2016-02-01

    Hepatitis E is considered to be a worldwide public health problem. Although the prevalence of hepatitis E virus (HEV) antibodies in healthy individuals is noted to be 11%, no patients with acute hepatitis E have previously been identified in Mongolia. Three hundred two consecutive patients (183 males and 119 females; median age of 22.0 [Interquartile range: 18.3-25.0] years) who were clinically diagnosed with sporadic acute hepatitis during 2012-2013 in Ulaanbaatar, Mongolia, were studied. By serological and/or molecular approaches, 77 (25.5%), 93 (30.8%), 19 (6.3%), 48 (15.9%), and 12 (4.0%) of the patients were diagnosed with acute hepatitis of types A, B, C, D (superinfection of hepatitis delta virus on a background of chronic hepatitis B virus infection) and E, respectively, while the cause of hepatitis was unknown in the remaining 53 patients (17.5%). The 12 hepatitis E patients had no history of travel abroad in the 3 months before the onset of disease, and lived separately in fixed or movable houses with water supplied via pipe, tank or well, denying transmission from a common water supply. The 12 HEV isolates obtained from the patients showed high nucleotide identities of 99.7-100%, and a representative HEV isolate, MNE13-227, was closest to the Chinese isolates of genotype 4, with the highest identity of 97.3% in the 304-nt ORF2 sequence and 92.1% over the entire genome. The present study revealed the occurrence of autochthonous acute hepatitis E in Mongolia, caused by a monophyletic genotype 4 HEV strain.

  10. Clinical significance of hepatic derangement in severe acute espiratory syndrome

    Institute of Scientific and Technical Information of China (English)

    Henry Lik-Yuen Chan; Ambrose Chi-Pong Kwan; Ka-Fai To; Sik-To Lai; Paul Kay-Sheung Chan; Wai-Keung Leung; Nelson Lee; Alan Wu; Joseph Jao-Yiu Sung

    2005-01-01

    AIM: Elevation of alanine aminotransferase (ALT) level iscommonly seen among patients suffering from severe acute respiratory syndrome (SARS). We report the progression and clinical significance of liver derangement in a large cohort of SARS patient.METHODS: Serial assay of serum ALT was followed in patients who fulfilled the WHO criteria of SARS. Those with elevated ALT were compared with those with normal liver functions for clinical outcome. Serology for hepatitis B virus (HBV) infection was checked. Adverse outcomes were defined as oxygen desaturation, need of intensive care unit (ICU) and mechanical ventilation and death.RESULTS: Two hundred and ninety-four patients wereincluded in this study. Seventy (24%) patients had elevatedserum ALT on admission and 204 (69%) patients hadelevated ALT during the subsequent course of illness. Using peek ALT >5xULN as a cut-off and after adjusting for potential confounding factors, the odds ratio of peek ALT >5x ULN for oxygen desaturation was 3.24 (95%CI 1.23-8.59, P = 0.018), ICU care was 3.70 (95%CT 1.38-9.89, P = 0.009), mechanical ventilation was 6.64 (95%CI 2.22-19.81, P = 0.001) and death was 7.34 (95%CI 2.28-24.89, P = 0.001). Ninety-three percent of the survived patients had ALT levels normalized or were on the improving trend during follow-up. Chronic hepatitis B was not associated with worse clinical outcomes. CONCLUSION: Reactive hepatitis is a common complication of SARS-coronavirus infection. Those patients with severehepatitis had worse clinical outcome.

  11. Acute Viral Hepatitis A – Clinical, Laboratory and Epidemiological Characteristics

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    Melinda HORVAT

    2013-06-01

    Full Text Available Background and Aims: Infection with hepatitis A virus is still one of the most common causes of hepatitis worldwide. The clinical manifestation of acute hepatitis A (AHA in adults can vary greatly, ranging from asymptomatic infection to severe and fulminant hepatitis. The aim of this study was to describe the demographic, clinical characteristics, laboratory features and hospital outcome of adult patients with AHA over a consecutive period of 4 years within an area from Eastern European country. Methods: Two hundred and two adult patients diagnosed with AHA were retrospective, observational and analytic analized over a period of 4 years. Based on prothrombin time less than 50, the study group was stratified in medium (79.2% and severe forms (20.8%. We investigated the clinical, laboratory and epidemiological features. Statistical analysis were applied to compare the medium and severe forms of AHA. Results: Most patients (72.7% were younger than 40 years. The main symptoms included: dyspepsia (72.07%, jaundice (86.63%, asteno-adynamia (86.72%, and flu-like symptoms (53.46%. The hemorrhagic cutaneous-mucous manifestations (6.93% associated with the severe forms of AHA (OR =12.19, 95%CI -3.59 - 41.3, p =0.001. We found statistically significant differences for PT (p <0.001, INR (p <0.001, TQ (p <0.001, ALAT (p <0.001, ASAT (p <0.001, ALP (p <0.001 and platelets (p =0.009 between severe and medium AHA forms. We found that TQ, INR, ALAT and ASAT have the highest diagnostic values, statistically significant (p <0.05 for severe AHA forms with AUC (0.99, 0.99, 0.72, 0.70 at values of sensitivity (95%, 90.5%, 89%, 95% and specificity (98%, 99%, 88%,94%. Conclusions Medium severity AHA forms were found in most of the study group patients (79.2%. The severe AHA forms were associated with hemorrhagic cutaneous-mucous manifestations (OR =12.19, p =0.001. The univariate analysis proved a negatively statistically significant correlation between IP and ALAT

  12. Acute viral hepatitis in Lebanon: evidence for a HAV-like non-A non-B hepatitis.

    Science.gov (United States)

    Shamma'a, M H

    1984-02-01

    Ninety-three cases of acute viral hepatitis in adult Lebanese patients were followed-up prospectively for a period ranging from 6 to 18 months. These included 33 hepatitis A (HAV), 32 hepatitis B (HBV) and 21 non-A, non-B hepatitis (NANB) cases. The clinical and seroepidemiologic characteristics of the three types were evaluated. HAV was characterized by a short prodroma (less than 1 week) and a high IgM level. HBV did not differ from similar cases reported in the Western world except for a complete absence of male homosexuals and drug addicts as a possible route of transmission. NANB hepatitis in Lebanon is mainly a sporadic infection similar to HAV except that the prodromal phase is prolonged (greater than 14 days) and IgM levels are within normal limits. The failure to develop chronicity in NANB suggests that the virus of sporadic NANB may be different from that which causes post-transfusional (PTH) NANB.

  13. Hepatitis e and acute liver failure in pregnancy.

    Science.gov (United States)

    Shalimar; Acharya, Subrat K

    2013-09-01

    Hepatitis E virus is a positive strand RNA virus with three open reading frames which is transmitted predominantly through the fecal contamination of water and food. It is the most common cause of acute liver failure in endemic areas. Pregnant women especially from the Indian subcontinent and Africa are at increased risk of contracting acute HEV infection as well as developing severe complications including ALF. Transmission of HEV occurs from mother to unborn child. Both maternal and fetal complications may occur, including abortion, fetal demise, preterm labor and maternal or neonatal death. The precise reasons for increased susceptibility to HEV infection during pregnancy and associated severe disease are still an enigma. Management is supportive and termination of pregnancy is not recommended as a general rule. Prevention of infection is of vital importance, as availability of clean drinking water can reduce the burden of this disease in the community. There is a need for future research to focus on prevention of ALF in pregnancy and to study the disease pathogenesis, which is not explicitly understood at present. The availability of a vaccine may alter the natural course of the disease in this select population which is at risk.

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

    Science.gov (United States)

    Hutin, Y J; Harpaz, R; Drobeniuc, J; Melnic, A; Ray, C; Favorov, M; Iarovoi, P; Shapiro, C N; Woodruff, B A

    1999-08-01

    Two case-control studies were conducted between January 1994 and August 1995 to determine the relative importance of injections and other exposures as a source of acute hepatitis B in Moldova among adults (aged 15 years) and children (aged 2-15 years). Results showed that injections in various health care settings were associated with acute hepatitis B and showed a higher proportion among adults compared with children. Contact with an HBsAg-positive person was also associated with illnesses; however, there was no statistically significant association between acute hepatitis B and other exposures. The risk of HBV transmission following percutaneous exposure is high (at least 30%). Calculation of the population attributable to risk suggests that injections associated with acute hepatitis B cases occurred in adults (52%) and children (21%). Adverse effects of injections may not be apparent in causing chronic infections. Transmission of blood-borne pathogens through unsafe injection practices is a problem increasingly identified worldwide.

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

    Science.gov (United States)

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

    2014-10-01

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

  16. "Pseudotumoral" hepatic pattern in acute alcoholic hepatitis:A case report

    Institute of Scientific and Technical Information of China (English)

    Andrea Tenca; Sara Massironi; Agostino Colli; Guido Basilisco; Dario Conte

    2009-01-01

    In acute alcoholic hepatitis (AAH),a "pseudotumoral" appearance of the liver parenchyma on computed tomography (CT) scan has been reported.The main findings are hypervascularized areas closely similar to those observed in large hepatocellular carcinomas.We report a case of a patient affected by AAH with an unusual appearance of these "pseudotumoral" areas on CT scan,close resembling a metastatic cancer rather than a primary hepatocellular carcinoma.In fact,in contrast with previous reports,the picture was characterized by the presence of many inhomogeneous,hypoattenuated areas highlighted during both pre-and post-contrast phases.Moreover,we report the first description of "pseudotumoral" lesions on ultrasound scan.This patient was successfully treated with corticosteroids,even if many controversies still exist regarding their efficacy in this setting.

  17. IMMUNOHISTOCHEMICAL STUDY OF EXTRACELLULAR-MATRIX IN ACUTE GALACTOSAMINE HEPATITIS IN RATS

    NARCIS (Netherlands)

    JONKER, AM; DIJKHUIS, FWJ; BOES, A; HARDONK, MJ

    1992-01-01

    A single injection of D-galactosamine hydrochloride induces acute self-limiting liver disease in rats that morphologically resembles drug-induced hepatitis in human beings. In this immunohistochemical study we examined the localization and expression of the hepatic extracellular matrix components fi

  18. Flumazenil does not improve hepatic encephalopathy associated with acute ischemic liver failure in the rabbit

    NARCIS (Netherlands)

    C.C.D. van der Rijt (Carin); R.J. de Knegt (Robert); S.W. Schalm (Solko); O.T. Terpstra (Onno); K. Mechelse (Karel)

    1990-01-01

    textabstractThe effect of flumazenil, a benzodiazepine antagonist, on hepatic encephalopathy was studied in rabbits with acute hepatic failure induced by a two-stage liver devascularization procedure. The rabbits were randomized for treatment with 5 mg/kg of flumazenil or the placebo. The drug was a

  19. Ultrasonographic Findings of the Gallbladder in Patients with Acute Hepatitis A: Do They Have Clinical Relevance?

    Energy Technology Data Exchange (ETDEWEB)

    An, Ji Young; Kim, Hyoung Jung; Lee, Dong Ho; Lim, Joo Won; Ko, Young Tae; Choi, Bong Keun [Dept. of Radiology, Graduate School of Medicine, Kyung Hee University, Kyung Hee University Medical Center, Seoul (Korea, Republic of)

    2012-06-15

    To determine the association of gallbladder (GB) abnormalities on ultrasonography (US) of patients with acute hepatitis A with demographic, clinical, and biochemical factors, and with other US findings. This retrospective study was approved by our institutional review board, which waived the requirement for informed consent. We retrospectively evaluated 152 consecutive patients with acute hepatitis A who underwent US. The diagnosis of acute hepatitis A was made during acute illness by demonstrating anti- HAV of the IgM class. US images were reviewed simultaneously by two abdominal radiologists and a consensus was reached for GB wall thickening, GB collapse, lymphadenopathy, and hepatic echogenicity. The associations between demographic, clinical, biochemical, and US findings and GB wall thickening or collapse were then assessed. GB wall thickening was present in 123 (81%) and GB collapse in 96 (63%) of the 152 patients. Total bilirubin level and GB collapse differed significantly (p < 0.05) between patients with and without GB wall thickening. Gender ratio, total and peak total bilirubin level, and GB wall thickness differed significantly (p < 0.05) between patients with and without GB collapse. Multivariate analysis showed that GB wall thickening was associated with GB collapse and vice versa. GB wall thickening and GB collapse are common US abnormalities associated with each other in patients with acute hepatitis A. However, GB wall thickening or collapse is not associated with any demographic, clinical, or biochemical factors, or with other US findings, in patients with acute hepatitis A.

  20. [Sodium butyrate inhibits HMGB1 expression and release and attenuates concanavalin A-induced acute liver injury in mice].

    Science.gov (United States)

    Gong, Quan; Chen, Mao-Jian; Wang, Chao; Nie, Hao; Zhang, Yan-Xiang; Shu, Ke-Gang; Li, Gang

    2014-10-25

    The purpose of the present study is to explore the protective effects of sodium butyrate (SB) pretreatment on concanavalin A (Con A)-induced acute liver injury in mice. The model animals were first administered intraperitoneally with SB. Half an hour later, acute liver injury mouse model was established by caudal vein injection with Con A (15 mg/kg). Then, levels of serous alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using standard clinical method by an automated chemistry analyzer, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured by ELISA, and pathological changes in hepatic tissue were observed by using HE staining and light microscopy. The expression and release of high-mobility group box 1 (HMGB1) were assessed by using reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and ELISA. The results showed that the pretreatment of SB significantly protected Con A-treated mice from liver injury as evidenced by the decrease of serum ALT, AST (P < 0.01) and reduction of hepatic tissues necrosis. SB also decreased levels of serous TNF-α and IFN-γ (P < 0.01). Furthermore, the expression and release of HMGB1 were markedly inhibited by SB pretreatment (P < 0.05 or P < 0.01). These results suggest that the attenuating effect of SB on Con A-induced acute liver injury may be due to its role of reducing the TNF-α and IFN-γ production, and inhibiting HMGB1 expression and release.

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

    Science.gov (United States)

    Arcana, Ronald; Frisancho, Oscar

    2011-01-01

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

  2. Acute hepatitis C: changing epidemiology and association with HIV infection.

    Science.gov (United States)

    Brejt, Nick; Gilleece, Yvonne; Fisher, Martin

    2007-03-01

    Over the past 6 to 7 years an increasing incidence of acute hepatitis C virus (AHCV) has been fuelled by two different changing epidemics: (1) a new resurgence of AHCV amongst intravenous drug users (IVDU); and (2) presumed sexually transmitted AHCV amongst predominantly HIV-positive men who have sex with men (MSM). Increasing incidence amongst IVDUs is likely to be a consequence of changing injecting behaviour, possibly related to changes in perception of HIV as well as HCV risk and consequences. Increasing incidence amongst MSM is likely to be a consequence of changing sexual practices, for example number of sexual partners and type of sexual behaviour, as well as increasing availability of recreational drugs associated with sexual risk-taking, and wider availability of casual sexual partners via the internet or sex-on-premises venues. It remains unclear whether the current outbreaks in MSM, predominantly seen in HIV-positive individuals, reflect a predisposition to AHCV secondary to HIV status per se, or whether this reflects differences in behaviour amongst HIV-positive versus HIV-negative MSM, or potentially increased screening (either routine or secondary to abnormal liver function tests) in HIV-positive MSM. The majority of individuals with AHCV are asymptomatic and therefore routine screening of individuals in at-risk groups with abnormal liver function tests should be considered. Previous historical studies suggest that individuals with concomitant HIV infection are far less likely than those without to spontaneously clear HCV. It is currently recommended that such individuals acutely infected with HCV should undergo monitoring of HCV viral load levels to determine whether spontaneous clearance is likely or whether the opportunity for early treatment should be considered.

  3. Thrombocytopenic purpura as initial presentation of acute hepatitis A.

    Science.gov (United States)

    Scott, Julius Xavier; Gnananayagam, Ebor Jacob; Gupta, Sanjay; Simon, Anna; Mukhopadhya, Ashish

    2003-01-01

    Extrahepatic immune manifestations are rare in hepatitis A virus infection. We report a 4 1/2-year-old girl who presented with thrombocytopenic purpura as initial manifestation of hepatitis A virus infection. She responded to steroid therapy.

  4. A Prospective, Randomized Investigation of Plasma First Resuscitation for Traumatic Hemorrhage and Attenuation of Acute Coagulopathy of Trauma

    Science.gov (United States)

    2016-05-01

    Attenuation of Acute Coagulopathy of Trauma . PRINCIPAL INVESTIGATOR: Ernest E. Moore, MD CONTRACTING ORGANIZATION: University of Colorado Denver...Randomized Investigation of “Plasma First Resuscitation” for Traumatic Hemorrhage and Attenuation of Acute Coagulopathy of Trauma . 5b. GRANT NUMBER...NOTES 14. ABSTRACT The COMBAT (Control of Major Bleeding After Trauma ) study is a randomized clinical trial evaluating the early administration of

  5. Infección aguda por el VHB Acute infection by Hepatitis B Virus

    Directory of Open Access Journals (Sweden)

    F. Alegre

    2004-01-01

    Full Text Available El espectro clínico de la infección aguda por el virus de la hepatitis B es muy amplio, con cuadros que van desde una hepatitis anictérica y subclínica a una hepatitis ictérica aguda grave e incluso, en algunos casos, a una hepatitis fulminante. El diagnóstico depende en gran medida del grado de sospecha clínica de la hepatitis, estableciéndose el origen etiológico por el virus B mediante el estudio de marcadores serológicos y/o DNA en sangre. Aunque en la mayor parte de los casos la evolución de la hepatitis aguda por virus B es favorable, con resolución espontánea de la clínica en 4-8 semanas, no es infrecuente en ciertos casos, sobre todo en la infancia, la progresión a hepatitis crónica. No existe ningún tratamiento específico para la infección aguda por virus B que reduzca su gravedad o prevenga su evolución a hepatitis crónica. Se recomienda, no obstante, el reposo relativo, y la administración de una dieta hipercalórica. En las hepatitis agudas graves debe indicarse ingreso hospitalario; en casos de hepatitis fulminante ingreso en UCI para monitorización intensiva y valoración de trasplante hepático si no se produce mejoría espontánea. En el presente artículo se revisa, de forma breve y esquemática, la clínica, el diagnóstico, el pronóstico y el tratamiento de la infección aguda por el virus de la hepatitis B.The clinical spectrum of acute hepatitis B virus infection is very broad, with clinical manifestations that range from anicteric and sub-clinical hepatitis to severe acute icteric hepatitis and even, in some cases, to fulminant hepatitis. Diagnosis depends to a large extent on the degree of clinical suspicion of hepatitis, establishing the aetiological origin of the B virus through the study of serological markers and/or DNA in the blood. Although in the majority of cases there is a favourable evolution of acute hepatitis B virus infection, with spontaneous resolution of the clinical manifestations

  6. Ghrelin reduces liver impairment in a model of concanavalin A-induced acute hepatitis in mice

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    Mao YQ

    2015-09-01

    activated the PI3K/Akt/Bcl-2 pathway and inhibited activation of autophagy.Conclusion: Our results demonstrate that ghrelin attenuates Con A-induced acute immune hepatitis by activating the PI3K/Akt pathway and inhibiting the process of autophagy, which might be related to inhibition of inflammatory cytokine release, and prevention of hepatocyte apoptosis. These effects could be interrupted by an Akt kinase inhibitor.Keywords: PI3K/Akt pathway, autophagy, inflammation, apoptosis

  7. Hepatic effect of NAC on sevear acute pancteatise of rats

    Institute of Scientific and Technical Information of China (English)

    Fang Chen; Ye-Jiang Zhou

    2014-01-01

    Objective:To analyze the hepatic protection of n-acetyl cysteine(NAC) on severe acute pancreatitis(SAP).Methods:SD rats were randomly divided into control group,SAP group and NAC group.SAPAHO method was adopted to establish the model,2 h after modeling, rats inNAC group had intraperitoneal injection ofNAC(200 mg/kg).Ten rats from each group were sacrificed in every6 and12 h at different time points respectively.Liver damage, liver function and serum amylase,AST,ALT and malondialdehyde(MDA) were determined.Results:Serum amylase,AST, ALT andMDA content inSAP,NAC group at each time point were significantly higher in the control group(P<0.05), serum amylase,AST,ALT andMDA content inNAC group rats were lower in theSAP group significantly(P<0.05);Microscopic examination showed that the liver injury in rats and theNAC group significantly reduced in theSAP group.Conclusions:NAC provides effective protection against liver damage toSAP, protective fromSAP liver injury.

  8. N-acetyl cysteine therapy in acute viral hepatitis

    Institute of Scientific and Technical Information of China (English)

    Huseyin Gunduz; Oguz Karabay; Ali Tamer; Resat Ozaras; Ali Mert; Omer Fehmi Tabak

    2003-01-01

    AIM: To investigate the effect of N-acetyl cysteine (NAC)on acute viral hepatitis (AVH).METHODS: We administered 200 mg oral NAC three times daily (600 mg/day) to the study group and placebo capsules to the control group. All patients were hospitalized and diagnosed as AVH. Blood total and direct bilirubin, ALT, AST,alkaline phosphatese, albumin and globulin levels of each patient were measured twice weekly until total bilirubin level dropped under 2 mg/dl, ALT level under 100 U/L, follow up was continued and then the patients were discharged.RESULTS: A total of 41(13 female and 28 male) AVH patients were included in our study. The period for normalization of ALT and total bilirubin in the study group was 19.7±6.9 days and 13.7±8.5 days respectively. In the control group it was 20.4±6.5 days and 16.9±7.8 days respectively (P>0.05).CONCLUSION: NAC administration effected neither the time necessary for normalization of ALT and total bilirubin values nor duration of hospitalization, so we could not suggest NAC for the treatment of icteric AVH cases. However, our results have shown that this drug is not harmful to patients with AVH.

  9. [Risk of acute hepatic insufficiency in children due to chronic accidental overdose of paracetamol (acetaminophen)

    NARCIS (Netherlands)

    Hameleers-Snijders, P.; Hogeveen, M.; Smeitink, J.A.M.; Kramers, C.; Draaisma, J.M.T.

    2007-01-01

    Two girls aged 4 and 3 years, respectively, experienced acute liver failure due to accidental ingestion of supratherapeutic doses of paracetamol (90 mg/kg/day or more). Recognition of chronic paracetamol intoxication as a cause of acute hepatic failure is often delayed. It is important to consider t

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

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    Husain Syed A

    2011-05-01

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

  11. Serological profile of sporadic acute viral hepatitis in an area of hyper-endemic hepatitis B virus infection

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    Ayoola Ayobanji

    2001-01-01

    Full Text Available Background: Located in the south western part of Saudi Arabia, the Gizan region is largely a rural community in which hepatitis B and chronic liver disease including hepatocellular carcinoma are highly prevalent. Aim of study: To determine the relative frequencies of acute hepatitis A, B, C and E in acute viral hepatitis in an area of hyperendemic hepatitis B infection. Methods and materials: In a prospective study 246 consecutive patients (179 males and 67 females diagnosed in a 2-year period were tested for markers of Hepatitis A virus (HAV, hepatitis B virus (HBV, hepatitis C (HCV and hepatitis E virus (HEV. Results: Of the patients tested, 131 (53.3% were children (< 10 years, and 42 (17% were 11 - 20 years in age. Ig M anti -HAV, IgM anti-HBV, anti- HCV and IgM anti-HEV were positive in 37%, 19.1%, 3.7% and 13.7% respectively. Markers of these viruses were absent in 24.4%. Among 131 children (< 10 years the commonest cause of AVH was HAV occurring in 57.3% of the cases. In adults (> 21 years HBV was found in 35.6% and IgM anti -HAV was detected in only 6.8%. In contrast to the age- related decline in the frequency of acute HA, the proportion of acute HE were similar in all age groups (13.7% in children, 16.7% in adolescents and 11.0% in adults. Conclusion: The study indicated that HAV is still a common cause of AVH particularly among children in Gizan. Acute 1-113 had a low occurrence among the children, evidently as a consequence of the integration of HB vaccine into the Saudi Arabian national EPI, 10 years ago. With the availability of combined HB and HA vaccines, It should be possible to graft the vaccination against HAV on to the existing program in Saudi Arabia. Affecting 13.4% of the group studied, sporadic HEV constitute a significant cause of AVH in this population. Until HEV vaccine becomes widely available, its prevention would be mainly by the improvement of socio - economic and hygienic standards of the population.

  12. Epidemiological aspects of acute viral hepatitis in São Paulo, Brazil

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    L. C. da Silva

    1986-12-01

    Full Text Available As few reports on the prevalence of each type of viral hepatitis have been published in our country, we studied 154 patients with acute viral hepatitis consecutively seen at the Liver Unit from November 1980 to November 1984. The frequency of hepatitis A, B and non-A, non-B was 52.6%, 27.3% and 20.1% respectively. Greater frequency in young people, previous contact with infected patients and ingestion of suspected foods were the predominant epidemiological features in the hepatitis A group. Hepatitis B was characterized by the parenteral, non-transfusional exposure, previous contact and a high occurence in health-care workers. A history of blood transfusion was a significant finding in the hepatitis non-A, non-B group. Finally, the routes of transmission were unknown in 30-40% of the three groups of patients.

  13. Relationship between antioxidant capacity and oxidative stress in children with acute hepatitis A

    Institute of Scientific and Technical Information of China (English)

    Mustafa Cemek; Semiha Dede; Fahri Bayiro(g)lu; Hüseyin (C)aksen; Fatma Cemek; Nihat Mert

    2006-01-01

    AIM: To investigate in children with acute hepatitis A.According to our knowledge, there are no data about the blood levels of malondialdehyde (MDA, an indicator of oxidative stress) and nonenzymic antioxidants in children with acute hepatitis A.METHODS: Whole blood MDA and reduced glutathione (GSH), serum β-carotene, retinol, vitamin E and vitamin C levels were studied in 19 (10 females, 9 males)children with acute hepatitis A and in 29 (13 females, 16males) healthy control subjects.RESULTS: There was a statistically significant difference between patients and controls for all parameters (P <0.05). Lipid peroxidation marker MDA was significantly elevated (P < 0.001), while antioxidants β-carotene,retinol and GSH were significantly decreased (all P <0.001) in patients compared to healthy subjects. In addition, α-tocopherol and ascorbic acid levels were significantly lower in patients when compared to age and sex matched controls (P < 0.05, P < 0.01, respectively).CONCLUSION: Our study shows that hepatitis A virus induces oxidative stress in childern with hepatitis A. This finding could be taken into consideration to improve the therapeutic approach in acute hepatitis A.

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

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    Bruno da Cruz Pádua

    2014-01-01

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

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

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    Blystad Hans

    2011-05-01

    Full Text Available Abstract Background Norway is classified as a low prevalence country for hepatitis B virus infection. Vaccination is only recommended for risk groups (intravenous drug users (IDUs, Men who have Sex with Men (MSM, immigrants and contacts of known carriers. We describe the epidemiology of reported cases of hepatitis B in Norway, during the years 1992-2009 in order to assess the validity of current risk groups and recommend preventive measures. Methods We used case based data from the national surveillance system on acute and chronic hepatitis B. The Norwegian Statistics Bureau provided population and migration data and the Norwegian Institute for Alcohol and Drug Research the estimated number of active IDUs between 2002-2007. Incidence rates (IR and incidence rate ratios (IRR for acute hepatitis B and notification rates (NR and notification rate ratios (NRR for chronic hepatitis B with 95% confidence intervals were calculated. Results The annual IR of acute hepatitis B ranged from 0.7/100,000 (1992 to 10.6/100,000 (1999. Transmission occurred mainly among IDUs (64% or through sexual contact (24%. The risk of acquiring acute hepatitis B was highest in people aged 20-29 (IRR = 6.6 [3.3-13.3], and in males (IRR = 2.4 [1.7-3.3]. We observed two peaks of newly reported chronic hepatitis B cases in 2003 and 2009 (NR = 17.6/100,000 and 17.4/100,000, respectively. Chronic hepatitis B was more likely to be diagnosed among immigrants than among Norwegians (NRR = 93 [71.9-120.6], and among those 20-29 compared to those 50-59 (NRR = 5.2 [3.5-7.9]. Conclusions IDUs remain the largest risk group for acute hepatitis B. The observed peaks of chronic hepatitis B are related to increased immigration from high endemic countries and screening and vaccination of these groups is important to prevent further spread of infection. Universal screening of pregnant women should be introduced. A universal vaccination strategy should be considered, given the high cost of

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

    Science.gov (United States)

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

    2015-02-01

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

  17. Chinese green tea and acute hepatitis: a rare yet recurring theme.

    Science.gov (United States)

    Lugg, Sebastian Thomas; Braganza Menezes, Darryl; Gompertz, Simon

    2015-09-23

    A previously healthy 16-year-old girl presented with signs of acute hepatitis. On initial enquiry, she had not taken any prescribed or 'over-the-counter' medications, and there was no recent travel history. Further investigations revealed no viral, autoimmune or metabolic cause of hepatitis. Only following specific questioning did she reveal that she had, in the preceding 3 months, regularly consumed internet ordered Chinese green tea, which contained Camellia sinensis. After ceasing green tea consumption, there was a rapid and sustained recovery of her hepatitis. The authors discuss the probable cause of herbal tea in this case of acute hepatitis, and the importance of awareness of this rare yet recurring theme for patients and clinicians alike.

  18. Opuntia ficus indica (nopal) attenuates hepatic steatosis and oxidative stress in obese Zucker (fa/fa) rats.

    Science.gov (United States)

    Morán-Ramos, Sofía; Avila-Nava, Azalia; Tovar, Armando R; Pedraza-Chaverri, José; López-Romero, Patricia; Torres, Nimbe

    2012-11-01

    Nonalcoholic fatty liver disease (NAFLD) is associated with multiple factors such as obesity, insulin resistance, and oxidative stress. Nopal, a cactus plant widely consumed in the Mexican diet, is considered a functional food because of its antioxidant activity and ability to improve biomarkers of metabolic syndrome. The aim of this study was to assess the effect of nopal consumption on the development of hepatic steatosis and hepatic oxidative stress and on the regulation of genes involved in hepatic lipid metabolism. Obese Zucker (fa/fa) rats were fed a control diet or a diet containing 4% nopal for 7 wk. Rats fed the nopal-containing diet had ∼50% lower hepatic TG than the control group as well as a reduction in hepatomegaly and biomarkers of hepatocyte injury such as alanine and aspartate aminotransferases. Attenuation of hepatic steatosis by nopal consumption was accompanied by a higher serum concentration of adiponectin and a greater abundance of mRNA for genes involved in lipid oxidation and lipid export and production of carnitine palmitoyltransferase-1 and microsomal TG transfer proteins in liver. Hepatic reactive oxygen species and lipid peroxidation biomarkers were significantly lower in rats fed nopal compared with the control rats. Furthermore, rats fed the nopal diet had a lower postprandial serum insulin concentration and a greater liver phosphorylated protein kinase B (pAKT):AKT ratio in the postprandial state. This study suggests that nopal consumption attenuates hepatic steatosis by increasing fatty acid oxidation and VLDL synthesis, decreasing oxidative stress, and improving liver insulin signaling in obese Zucker (fa/fa) rats.

  19. Hepatitis B virus disrupts mitochondrial dynamics: induces fission and mitophagy to attenuate apoptosis.

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    Seong-Jun Kim

    Full Text Available Human hepatitis B virus (HBV causes chronic hepatitis and is associated with the development of hepatocellular carcinoma. HBV infection alters mitochondrial metabolism. The selective removal of damaged mitochondria is essential for the maintenance of mitochondrial and cellular homeostasis. Here, we report that HBV shifts the balance of mitochondrial dynamics toward fission and mitophagy to attenuate the virus-induced apoptosis. HBV induced perinuclear clustering of mitochondria and triggered mitochondrial translocation of the dynamin-related protein (Drp1 by stimulating its phosphorylation at Ser616, leading to mitochondrial fission. HBV also stimulated the gene expression of Parkin, PINK1, and LC3B and induced Parkin recruitment to the mitochondria. Upon translocation to mitochondria, Parkin, an E3 ubiquitin ligase, underwent self-ubiquitination and facilitated the ubiquitination and degradation of its substrate Mitofusin 2 (Mfn2, a mediator of mitochondrial fusion. In addition to conventional immunofluorescence, a sensitive dual fluorescence reporter expressing mito-mRFP-EGFP fused in-frame to a mitochondrial targeting sequence was employed to observe the completion of the mitophagic process by delivery of the engulfed mitochondria to lysosomes for degradation. Furthermore, we demonstrate that viral HBx protein plays a central role in promoting aberrant mitochondrial dynamics either when expressed alone or in the context of viral genome. Perturbing mitophagy by silencing Parkin led to enhanced apoptotic signaling, suggesting that HBV-induced mitochondrial fission and mitophagy promote cell survival and possibly viral persistence. Altered mitochondrial dynamics associated with HBV infection may contribute to mitochondrial injury and liver disease pathogenesis.

  20. [Acute hepatitis-associated pure red cell aplasia: a case report].

    Science.gov (United States)

    Della Loggia, Paolo; Cremonini, Laura

    2002-12-01

    After a holiday in Egypt, a 57-year-old caucasian woman developed acute hepatitis A. The illness seemed initially to have a benign course, with a decreasing trend of hepatic enzymes and an apparent recovery. Three weeks later a relapse occurred. Recurrence of symptoms and aminotransferase elevation were associated with severe anemia; a hyporegenerative anemia was diagnosed and all laboratory findings were consistent with pure red cell aplasia. The haematologic disorder was successfully treated with red cell transfusion and glucocorticoids.

  1. Crocin attenuates lipopolysacchride-induced acute lung injury in mice

    Science.gov (United States)

    Wang, Jian; Kuai, Jianke; Luo, Zhonghua; Wang, Wuping; Wang, Lei; Ke, Changkang; Li, Xiaofei; Ni, Yunfeng

    2015-01-01

    Crocin, a representative of carotenoid compounds, exerts a spectrum of activities including radical scavenger, anti-microbial and anti-inflammatory properties. To investigate the protective effect of crocin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. ALI was induced in mice by intratracheal instillation of LPS (1 mg/kg). The mice received intragastric injection of crocin (50 mg/kg) 1 h before LPS administration. Pulmonary histological changes were evaluated by hematoxylineosin stain and lung wet/dry weight ratios were observed. Concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and nitric oxide (NO), and myeloperoxidase (MPO) activity were measured by enzymelinked immunosorbent assay. Expression of inducible nitric oxide synthase (iNOS) in lung tissues was determined by Western blot analysis. Crocin pretreatment significantly alleviated the severity of lung injury and inhibited the production of TNF-α and IL-1β in mice with ALI. After LPS administration, the lung wet/dry weight ratios, as an index of lung edema, and MPO activity were also markedly reduced by crocin pretreatment. Crocin pretreatment also reduced the concentrations of NO in lung tissues. Furthermore, the expression of iNOS was significantly suppressed by crocin pretreatment. Croncin potently protected against LPS-induced ALI and the protective effects of crocin may attribute partly to the suppression of iNOS expression. PMID:26191176

  2. Acute Lymphoblastic Leukemia in a Young Adult Presenting as Hepatitis and Acute Kidney Injury

    Science.gov (United States)

    Heincelman, Marc; Karakala, Nithin; Rockey, Don C.

    2016-01-01

    Acute lymphoblastic leukemia (ALL) in adults is a relatively rare malignancy. The typical presentation includes signs and symptoms associated with bone marrow failure, including fevers, infections, fatigue, and excessive bruising. In this article, we report an unusual systemic presentation of ALL in a previously healthy 18-year-old man. He initially presented with several-day history of nausea and vomiting, 10-pound weight loss, and right upper quadrant abdominal pain with evidence of acute hepatocellular liver injury (elevations in aspartate aminotransferase/alanine aminotransferase) and elevation in serum creatinine. Further history revealed that he just joined the Marine Corp; in preparation, he had been lifting weights and taking protein and creatine supplements. A complete serological evaluation for liver disease was negative and creatine phosphokinase was normal. His aspartate aminotransferase and alanine aminotransferase declined, and he was discharged with expected improvement. However, he returned one week later with continued symptoms and greater elevation of aminotransferases. Liver biopsy was nondiagnostic, revealing scattered portal and lobular inflammatory cells (primarily lymphocytes) felt to be consistent with drug-induced liver injury or viral hepatitis. Given his elevated creatinine, unresponsive to aggressive volume expansion, a kidney biopsy was performed, revealing normal histology. He subsequently developed an extensive left lower extremity deep venous thrombosis. Given his deep venous thrombosis, his peripheral blood was sent for flow cytometry, which revealed lymphoblasts. Bone marrow biopsy revealed 78% blasts with markers consistent with acute B-cell lymphoblastic leukemia. This report emphasizes that right upper quadrant abdominal pain with liver test abnormalities may be the initial presentation of a systemic illness such as ALL.

  3. [Clinical and immunological features of acute hepatitis B in patients with concomitant chronic toxic liver damage].

    Science.gov (United States)

    Furyk, E; Ryabokon, E

    2013-02-01

    The article presents information obtained during the survey in 64 patients with acute hepatitis B. We show that acute hepatitis B in patients with concomitant chronic toxic liver characterized by a marked imbalance of cytokine status due to a lower level of interleukin-2 and a higher content of interleukin-8, the highest levels of nitrite content, spontaneous oxidative modifications of blood proteins and the lowest content of L -arginine in the blood serum in the dynamics of disease compared with patients without this concomitant factor. In the period of convalescence these changes in patients with acute hepatitis B with concomitant chronic toxic liver characterized combined with higher cytolysis of liver cells, often circulating in the blood of HBsAg seroconversion and less frequently with the advent of anti-HBeAg.

  4. Monoacylglycerol lipase (MAGL inhibition attenuates acute lung injury in mice.

    Directory of Open Access Journals (Sweden)

    Carolina Costola-de-Souza

    Full Text Available Endocannabinoid signaling is terminated by enzymatic hydrolysis, a process that, for 2-Arachidonoylglycerol (2-AG, is mediated by monoacylglycerol lipase (MAGL. The piperidine carbamate, 4-nitrophenyl- 4-(dibenzo[d] [1,3]dioxol-5-yl (hydroxy methyl piperidine- 1-carboxylate (JZL184, is a drug that inhibits MAGL and presents high potency and selectivity. Thus, JZL184 increases the levels of 2-AG, an endocannabinoid that acts on the CB1 and CB2 cannabinoid receptors. Here, we investigated the effects of MAGL inhibition, with a single dose (16 mg/kg, intraperitoneally (i.p. of JZL184, in a murine model of lipopolysaccharide (LPS -induced acute lung injury (ALI 6, 24 and 48 hours after the inflammatory insult. Treatment with JZL184 decreased the leukocyte migration into the lungs as well as the vascular permeability measured through the bronchoalveolar lavage fluid (BAL and histological analysis. JZL184 also reduced the cytokine and chemokine levels in the BAL and adhesion molecule expression in the blood and BAL. The CB1 and CB2 receptors were considered involved in the anti-inflammatory effects of JZL184 because the AM281 selective CB1 receptor antagonist (1-(2,4-dichlorophenyl-5-(4-iodophenyl-4-methyl-N-4-morpholinyl-1H-pyrazole-3-carboxamide and the AM630 selective CB2 receptor antagonist ([6-iodo-2-methyl-1-[2-(4-morpholinylethyl]-1H-indol-3-yl](4-methoxyphenyl-methanone blocked the anti-inflammatory effects previously described for JZL184. It was concluded that MAGL inhibition, and consequently the increase in 2-AG levels, produced anti-inflammatory effects in a murine model of LPS-induced ALI, a finding that was considered a consequence of the activation of the CB1 and CB2 receptors.

  5. Typhoid Fever Presenting With Acute Renal Failure And Hepatitis Simultaneously - A Rare Presentation

    Directory of Open Access Journals (Sweden)

    Rajput R.

    2016-05-01

    Full Text Available Typhoid fever is an important health problem worldwide but its incidence is more in developing countries. Hepatic involvement is common, but both hepatic and renal involvement is rare in typhoid fever. We report a case of typhoid fever presenting with hepatitis and acute renal failure. A 17 year old male presenting with fever and pain abdomen was found to have raised blood urea, creatinine, liver enzymes and bilirubin. Widal and typhidot (IgM,IgG test were positive. His symptoms subsided and deranged parameters resolved with treatment of typhoid fever.

  6. Review: Study progress on mechanism of severe acute pancreatitis complicated with hepatic injury

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xi-ping; WANG Lei; ZHANG Jie

    2007-01-01

    Study on the action mechanism of inflammatory mediators generated by the severe acute pancreatitis (SAP) in multiple organ injury is a hotspot in the surgical field. In clinical practice, the main complicated organ dysfunctions are shock, respiratory failure, renal failure, encephalopathy, with the rate of hepatic diseases being closely next to them. The hepatic injury caused by SAP cannot only aggravate the state of pancreatitis, but also develop into hepatic failure and cause patient death. Its complicated pathogenic mechanism is an obstacle in clinical treatment. Among many pathogenic factors, the changes ofvasoactive substances, participation of inflammatory mediators as well as OFR (oxygen free radical), endotoxin, etc. may play important roles in its progression.

  7. Hepatitis E virus quasispecies and the outcome of acute hepatitis E in solid-organ transplant patients.

    Science.gov (United States)

    Lhomme, Sebastien; Abravanel, Florence; Dubois, Martine; Sandres-Saune, Karine; Rostaing, Lionel; Kamar, Nassim; Izopet, Jacques

    2012-09-01

    Hepatitis E virus (HEV) infections are responsible for chronic hepatitis in immunocompromised patients, and this can evolve to cirrhosis. Like all RNA viruses, HEV exists as a mixture of heterogeneous viruses defining quasispecies. The relationship between the genetic heterogeneity described as a quasispecies, cytokine secretion, and the outcome of acute hepatitis in immunocompromised patients remains to be elucidated. We cloned and sequenced the region encoding the M and P capsid domains of HEV from eight solid-organ transplant (SOT) patients with acute HEV infection who subsequently cleared the virus and from eight SOT patients whose infection became chronic. We analyzed the cytokines and chemokines in the sera of these SOT patients by multianalyte profiling. The nucleotide sequence entropy and genetic distances were greater in patients whose infections became chronic. A lower K(a)/K(s) ratio was associated with the persistence of HEV. The patients who developed chronic infection had lower serum concentrations of interleukin-1 (IL-1) receptor antagonist and soluble IL-2 receptor. Increased concentrations of the chemokines implicated in leukocyte recruitment to the liver were associated with persistent infection. Those patients with chronic HEV infection and progressing liver fibrosis had less quasispecies diversification during the first year than patients without liver fibrosis progression. Great quasispecies heterogeneity, a weak inflammatory response, and high serum concentrations of the chemokines involved in leukocyte recruitment to the liver in the acute phase were associated with persistent HEV infection. Slow quasispecies diversification during the first year was associated with rapidly developing liver fibrosis.

  8. Prophylaxis of acute viral hepatitis by immune serum globulin, hepatitis B vaccine, and health education: a sixteen year study of Japan overseas cooperation volunteers.

    Science.gov (United States)

    Ohara, H; Ebisawa, I; Naruto, H

    1997-01-01

    From 1978 to 1993 a study of acute viral hepatitis contracted by the Japan Overseas Cooperation Volunteers (JOCV) during their assignments in tropical and subtropical countries was conducted. Of 10,509 subjects in this study, 240 cases of acute viral hepatitis were confirmed (hepatitis A = 139, hepatitis B = 72, and non-A, non-B hepatitis = 29). The annual morbidity was 5.1% in 1978 and 4.9% in 1979, with hepatitis A accounting for 80% of the cases. However, it decreased significantly after the prophylactic inoculation with immune serum globulin (ISG) was started in 1980. A significant decrease of hepatitis B from 1.2% in 1980 to 0.1% in 1990 was also seen after vaccination was introduced for all volunteers in 1988. Health education concerning food and water sanitation, and providing general information on viral hepatitis, was also conducted throughout this period. These results indicate that acute viral hepatitis could be successfully prevented in the JOCV with a combination of ISG, hepatitis B vaccination, and health education.

  9. [A case of sustained cholestasis caused by acute A viral hepatitis in Dubin-Johnson syndrome].

    Science.gov (United States)

    Ra, Sang Ho; Sung, Se Yong; Jung, Ho Yeon; Cha, Jae Hwang; Baik, Soon Koo; Cho, Mee Yon; Kim, Moon Young

    2012-04-01

    Dubin-Johnson syndrome is a rare clinical entity. It shows intermittent symptoms such as chronic or intermittent jaundice, abdominal pain, weakness, nausea, vomiting, anorexia and diarrhea. Symptoms are precipitated or aggravated by pregnancy, alcoholism, surgical procedures and intercurrent disease. Chronic idiopathic jaundice is typical of Dubin-Johnson syndrome and its prognosis is good. We describe a case of prolonged cholestasis for more than 10 months caused by acute A viral hepatitis in a patient with Dubin-Johnson syndrome. It is a first report of cholestasis complicated by acute A viral hepatitis in a patient with Dubin-Johnson syndrome.

  10. Novel controlled attenuation parameter for noninvasive assessment of steatosis using Fibroscan(®): validation in chronic hepatitis C.

    Science.gov (United States)

    Sasso, M; Tengher-Barna, I; Ziol, M; Miette, V; Fournier, C; Sandrin, L; Poupon, R; Cardoso, A-C; Marcellin, P; Douvin, C; de Ledinghen, V; Trinchet, J-C; Beaugrand, M

    2012-04-01

    A novel controlled attenuation parameter (CAP) has been developed for Fibroscan(®) to assess liver steatosis, simultaneously with liver stiffness measurement (LSM). We assessed CAP diagnostic accuracy in a large cohort of patients with chronic hepatitis C (CHC) virus. A total of 615 patients with CHC, who underwent both Fibroscan(®) and liver biopsy, were analysed. Fibrosis was graded using METAVIR score. Steatosis was categorized by visual assessment as S(0) : steatosis in Fibroscan(®) , in patients with CHC.

  11. Ceftriaxone attenuates locomotor activity induced by acute and repeated cocaine exposure in mice.

    Science.gov (United States)

    Tallarida, Christopher S; Corley, Gladys; Kovalevich, Jane; Yen, William; Langford, Dianne; Rawls, Scott M

    2013-11-27

    Ceftriaxone (CTX) decreases locomotor activation produced by initial cocaine exposure and attenuates development of behavioral sensitization produced by repeated cocaine exposure. An important question that has not yet been answered is whether or not CTX reduces behavioral sensitization to cocaine in cases in which the antibiotic is administered only during the period of cocaine absence that follows repeated cocaine exposure and precedes reintroduction to cocaine. We investigated this question using C57BL/6 mice. Mice pretreated with cocaine (15mg/kg×14 days) and then challenged with cocaine (15mg/kg) after 30 days of cocaine absence displayed sensitization of locomotor activity. For combination experiments, CTX injected during the 30 days of cocaine absence attenuated behavioral sensitization produced by cocaine challenge. In the case in which CTX was injected together with cocaine for 14 days, development of behavioral sensitization to cocaine challenge was also reduced. CTX attenuated the increase in locomotor activity produced by acute cocaine exposure; however, its efficacy was dependent on the dose of cocaine as inhibition was detected against 30mg/kg, but not 15mg/kg, of cocaine. These results from mice indicate that CTX attenuates locomotor activity produced by acute and repeated cocaine exposure and counters cocaine's locomotor activating properties in a paradigm in which the antibiotic is injected during the period of forced cocaine absence that follows repeated cocaine exposure.

  12. Attenuation of oxidative stress and alteration of hepatic tissue ultrastructure by D-pinitol in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Sivakumar, Selvaraj; Palsamy, Periyasamy; Subramanian, Sorimuthu Pillai

    2010-06-01

    The present study was aimed to investigate the effect of D-pinitol on hyperglycaemia mediated oxidative stress by analysing the hepatic antioxidant competence, pro-inflammatory cytokines and ultrastructural changes in liver tissues of streptozotocin-induced diabetic rats. Oral administration of D-pinitol (50 mg/kg b.w.) resulted in significant (p pinitol instigated a significant escalation in the levels of hepatic tissue non-enzymatic antioxidants and the activities enzymatic antioxidants of diabetic rats with significant (p pinitol on the hepatic tissues from oxidative stress-induced liver damage. These biochemical observations were complemented by histological and ultrastructural examination of liver section. Thus, the present study demonstrates the hepatoprotective nature of D-pinitol by attenuating hyperglycaemia-mediated pro-inflammatory cytokines and oxidative stress.

  13. A comparative study of regression of jaundice in patients of malaria and acute viral hepatitis

    Directory of Open Access Journals (Sweden)

    D.K. Kochar, K. Kaswan, S.K. Kochar, P. Sirohi, M. Pala, A. Kochar , R.P. Agrawal , A. Das

    2006-09-01

    Full Text Available Background & objectives: Jaundice is one of the common manifestations of severe malaria in adults.The purpose of this study is to compare the pattern of clinical and biochemical parameters such asserum bilirubin and liver enzyme levels in patients of malaria with jaundice and acute viral hepatitis.Methodology: The present study was conducted on 34 patients of malaria with jaundice and 15patients of acute viral hepatitis. Estimation of serum bilirubin, aspartate amino transferase (AST,alanine amino transferase (ALT and alkaline phosphatase was done daily using standard proceduresin malaria patients and weekly in acute viral hepatitis patients.Results: Mean level of serum bilirubin on first day in malaria and acute viral hepatitis patients was7.07 ± 3.94 and 10.38 ± 7.87 mg%, whereas on Day 8 it was 1.19 ± 1.43 and 7.88 ± 7.02 mg%respectively. Mean level of AST on Day 1 in malaria and acute viral hepatitis patients was 158.47 ±120.35 and 1418.6 ± 834.11 IU/L, whereas on Day 8 it was 41 ± 28.33 and 775.3 ± 399.01IU/L respectively. Mean level of ALT on Day 1 in malaria and acute viral hepatitis patients was220.14 ± 145.61 and 1666.67 ± 1112.77 IU/L, whereas on Day 8 it was 50.85 ± 37.31 and 823.8 ±475.06 IU/L respectively. Mean level of serum alkaline phosphatase on Day 1 in malaria and acuteviral hepatitis patients was 394.74 ± 267.78 and 513.4 ± 324.7 IU/L, whereas on Day 8 it was84.76 ± 68.50 and 369.27 ± 207.75 IU/L respectively.Interpretation & conclusion: We observed that resolution of jaundice in malaria took 1–2 weeks incontrast 6 to 8 weeks in viral hepatitis. This difference in duration was statistically significant. Thus,jaundice not resolving in 1–2 weeks time in a patient of malaria requires serious consideration forpresence of other concomitant diseases including viral hepatitis.

  14. Cluster of cases of acute hepatitis associated with hepatitis E virus infection acquired in the Netherlands.

    NARCIS (Netherlands)

    Widdowson, MA; Jaspers, WJ; Poel, van der WH; Verschoor, F.; Husman, AM de Roda; Winter, HL; Zaaijer, H.L.; Koopmans, M

    2003-01-01

    Increasing evidence suggests that hepatitis E virus (HEV) infection may occur in developed countries and that swine may act as a reservoir. We report a cluster of 2 confirmed cases and 1 presumptive case of hepatitis associated with HEV. The typed strain from 1 case was related to HEV strains found

  15. Acute Alcoholic Hepatitis | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available UK - MHRA A.2EudraCT number2006-004419-24 A.3Full title of the trial The Use of Sulfasalazine as an Anti-fibrotic in Acute...General Information on the Trial E.1 Medical condition or disease under investigation E.1.1Medical condition...(s) being investigated Acute Alcoholic Hepatitis MedDRA Classification E.1.2 Medical condition or disease un

  16. Extracorporal hemodialysis with acute or decompensated chronical hepatic failure

    Directory of Open Access Journals (Sweden)

    Wasem, Jürgen

    2006-04-01

    Full Text Available Background: Conventional diagnostic procedures and therapy of acute liver failure (ALF and acute-on-chronic liver failure (ACLF focus on to identify triggering events of the acute deterioration of the liver function and to avoid them. Further objectives are to prevent the development respectively the progression of secondary organ dysfunctions or organ failure. Most of the times the endocrinological function of the liver can to a wide extent be compensated, but the removal of toxins can only marginally be substituted by conventional conservative therapy. To improve this component of the liver function is the main objective of extracorporal liver support systems. The following principles of liver support systems can be differentiated: Artificial systems, bioartifical systems and extracorporal liver perfusion systems. This HTA report focuses on artificial systems (e.g. BioLogic-DT/-DTPF, MARS, Prometheus, because only these approaches currently are relevant in the German health care system. In 2004 a category "Extracorporal liver assist device" was introduced in the list of "additional payments" in the German DRG-system, which makes reimbursement for hospitals using the technology in inpatient care possible, based on an hospital's individual contract with statutory sickness funds. Objectives: To report the present evidence and future research need on medical efficacy and economic effectiveness of extracorporal liver support devices for treatment of patients with ALF or ACLF based on published literature data. Are artificial liver support systems efficient and effective in the treatment of ALF or ACLF? Methods: An extensive, systematic literature search in medical, economic, and HTA literature data bases was performed. Relevant data were extracted and synthesised. Results: Relevant controlled trials were detected for BioLogic-DT and MARS. No randomised controlled trial on Prometheus was found. None of the included studies on BioLogic-DT showed

  17. Acute sterol o-acyltransferase 2 (SOAT2 knockdown rapidly mobilizes hepatic cholesterol for fecal excretion.

    Directory of Open Access Journals (Sweden)

    Stephanie M Marshall

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

  18. Acute drug induced hepatitis secondary to a weight loss product purchased over the internet

    Directory of Open Access Journals (Sweden)

    Cross Tim JS

    2007-06-01

    Full Text Available Abstract Background Many people now seek alternative methods of weight loss. The internet provides a readily available source of weight reduction products, the ingredients of which are often unclear. The authors describe a case of acute hepatitis in a 20 year old woman caused by such a product purchased over the internet. Case Presentation A 20-year old woman presented with a two day history of abdominal pain, vomiting and jaundice. There were no identifiable risk factors for chronic liver disease. Liver function tests demonstrated an acute hepatitis (aminoaspartate transaminase 1230 IU/L. A chronic liver disease screen was negative. The patient had started a weight loss product (Pro-Lean, purchased over the internet two weeks prior to presentation. The patient was treated conservatively, and improved. The sequence of events suggests an acute hepatitis caused by an herbal weight loss product. Conclusion This case report highlights the dangers of weight loss products available to the public over the internet, and the importance of asking specifically about alternative medicines in patients who present with an acute hepatitis.

  19. Use of nucleoside (tide) analogues in patients with hepatitis B-related acute liver failure

    DEFF Research Database (Denmark)

    Dao, Doan Y; Seremba, Emmanuel; Ajmera, Veeral;

    2012-01-01

    The efficacy of nucleoside(tide) analogues (NA) in the treatment of acute liver failure due to hepatitis B virus (HBV-ALF) remains controversial. We determined retrospectively the impact of NAs in a large cohort of patients with HBV-ALF....

  20. Molecular epidemiology of acute hepatitis B in the Netherlands in 2004 : nationwide survey

    NARCIS (Netherlands)

    van Houdt, R; Bruisten, S M; Koedijk, F D H; Dukers, N H T M; Op de Coul, E L M; Mostert, M C; Niesters, H G M; Richardus, J H; de Man, R A; van Doornum, G J J; van den Hoek, J A R; Coutinho, R A; van de Laar, M J W; Boot, H J

    2007-01-01

    To gain insight into hepatitis B virus (HBV) transmission in the Netherlands, epidemiological data and sera were collected from reported cases of acute HBV infections in the Netherlands in 2004. Cases were classified according to mode of transmission. A fragment of the S-gene of HBV (648 bp) was amp

  1. Hepatitis A related acute liver failure by consumption of contaminated food

    NARCIS (Netherlands)

    Chi, Heng; Haagsma, Elizabeth B.; Riezebos-Brilman, Annelies; van den Berg, Arie P.; Metselaar, Herold J.; de Knegt, Robert J.

    2014-01-01

    We present a patient with no medical history admitted for jaundice and dark coloured urine. Further investigations revealed hepatitis A related acute liver failure while the patient had no travel history, nor contact with infected individuals. After admission, the patient deteriorated fulfilling the

  2. Boceprevir, peginterferon and ribavirin for acute hepatitis C in HIV infected patients

    NARCIS (Netherlands)

    Hullegie, Sebastiaan J.; Claassen, Mark A. A.; van den Berk, Guido E. L.; Van der Meer, Jan T. M.; Posthouwer, Dirk; Lauw, Fanny N.; Leyten, Eliane M. S.; Koopmans, Peter P.; Richter, Clemens; van Eeden, Arne; Bierman, Wouter F. W.; Newsum, Astrid M.; Arends, Joop E.; Rijnders, Bart J. A.

    2016-01-01

    Background & Aims: Acute hepatitis C virus infections (AHCV) are prevalent among HIV positive men having sex with men and generally treated with pegylated interferon-alpha (PegIFN) and ribavirin (RBV) during 24 weeks. The addition of a protease inhibitor could shorten therapy without loss of efficac

  3. A diet high in α-linolenic acid and monounsaturated fatty acids attenuates hepatic steatosis and alters hepatic phospholipid fatty acid profile in diet-induced obese rats.

    Science.gov (United States)

    Hanke, Danielle; Zahradka, Peter; Mohankumar, Suresh K; Clark, Jaime L; Taylor, Carla G

    2013-01-01

    This study investigated the efficacy of the plant-based n-3 fatty acid, α-linolenic acid (ALA), a dietary precursor of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for modulating hepatic steatosis. Rats were fed high fat (55% energy) diets containing high oleic canola oil, canola oil, a canola/flax oil blend (C/F, 3:1), safflower oil, soybean oil, or lard. After 12 weeks, C/F and weight-matched (WM) groups had 20% less liver lipid. Body mass, liver weight, glucose and lipid metabolism, inflammation and molecular markers of fatty acid oxidation, synthesis, desaturation and elongation did not account for this effect. The C/F group had the highest total n-3 and EPA in hepatic phospholipids (PL), as well as one of the highest DHA and lowest arachidonic acid (n-6) concentrations. In conclusion, the C/F diet with the highest content of the plant-based n-3 ALA attenuated hepatic steatosis and altered the hepatic PL fatty acid profile.

  4. Acute paraquat exposure impairs colonic motility by selectively attenuating nitrergic signalling in the mouse.

    Science.gov (United States)

    Diss, Lucy; Dyball, Sarah; Ghela, Tina; Golding, Jonathan; Morris, Rachel; Robinson, Stephen; Tucker, Rosemary; Walter, Talia; Young, Paul; Allen, Marcus; Fidalgo, Sara; Gard, Paul; Mabley, Jon; Patel, Bhavik; Chatterjee, Prabal; Yeoman, Mark

    2016-02-01

    Paraquat, a common herbicide, is responsible for large numbers of deaths worldwide through both deliberate and accidental ingestion. Previous studies have eluded that the bioavailability of paraquat increases substantially with increasing dose and that these changes may in part be due to the effects that these high concentrations have on the gastrointestinal tract (GI tract). To date, the actions of acute, high concentrations (20mM for 60 min) of paraquat on the GI tract, particularly the colon which is a major site of paraquat absorption, are unknown. This study examined the effects of acute paraquat administration on colonic motility in the C57BL/6 mouse. Acute paraquat exposure decreased colonic motility and the amplitude of colonic migrating motor complexes (CMMCs), which are major motor patterns involved in faecal pellet propulsion. In isolated segments of distal colon, paraquat increased resting tension and markedly attenuated electrical field stimulation-evoked relaxations. Pharmacological dissection of paraquat's mechanism of action on both the CMMCs and field stimulated tissue using the nitric oxide synthase inhibitor NG-nitro-L-arginine and direct measurement of NO release from the myenteric plexus, demonstrated that paraquat selectively attenuates nitrergic signalling pathways. These changes did not appear to be due to alterations in colonic oxidative stress, inflammation or complex 1 activity, but were most likely caused by paraquat's ability to act as a redox couple. In summary, these data demonstrate that acute paraquat exposure attenuates colonic transit. These changes may facilitate the absorption of paraquat into the circulation and so facilitate its toxicity.

  5. Aliskiren attenuates steatohepatitis and increases turnover of hepatic fat in mice fed with a methionine and choline deficient diet.

    Directory of Open Access Journals (Sweden)

    Kuei-Chuan Lee

    Full Text Available BACKGROUND & AIMS: Activation of the renin-angiotensin-system is known to play a role in nonalcoholic steatohepatitis. Renin knockout mice manifest decreased hepatic steatosis. Aliskiren is the first direct renin inhibitor to be approved for clinical use. Our study aims to evaluate the possible therapeutic effects and mechanism of the chronic administration of aliskiren in a dietary steatohepatitis murine model. METHODS: Male C57BL/6 mice were fed with a methionine and choline-deficient (MCD diet to induce steatohepatitis. After 8 weeks of feeding, the injured mice were randomly assigned to receive aliskiren (50 mg·kg(-1 per day or vehicle administration for 4 weeks. Normal controls were also administered aliskiren (50 mg·kg(-1 per day or a vehicle for 4 weeks. RESULTS: In the MCD mice, aliskiren attenuated hepatic steatosis, inflammation and fibrosis. Aliskiren did not change expression of lipogenic genes but increase turnover of hepatic fat by up-regulating peroxisome proliferator-activated receptor α, carnitine palmitoyltransferase 1a, cytochrome P450-4A14 and phosphorylated AMP-activated protein kinase. Furthermore, aliskiren decreased the hepatic expression of angiotensin II and nuclear factor κB. The levels of oxidative stress, hepatocyte apoptosis, activation of Kupffer cells and hepatic stellate cells, and pro-fibrotic markers were also reduced in the livers of the MCD mice receiving aliskiren. CONCLUSIONS: Aliskiren attenuates steatohepatitis and fibrosis in mice fed with a MCD diet. Thus, the noted therapeutic effects might come from not only the reduction of angiotensin II but also the up-regulation of fatty acid oxidation-related genes.

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

    Directory of Open Access Journals (Sweden)

    Khattab Mahmoud

    2009-11-01

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

  7. OUTCOME OF ACUTE LIVER FAILURE DUE TO HEPATITIS A TREATED WITH MEDICAL MANAGEMENT

    Directory of Open Access Journals (Sweden)

    Thulaseedharan Nallaveettil

    2016-02-01

    Full Text Available BACKGROUND Acute liver failure is a heterogeneous entity and its prognosis varies with the aetiology. In India and other developing countries, hepatitis A virus is an important cause of acute liver failure. The prognostic factors and outcome of such patients should be studied separately. AIM OF THE STUDY To study the outcome of patients with acute liver failure due to hepatitis A treated with intensive supportive care and to determine the prognostic factors predicting the transplant free survival. MATERIALS AND METHODS In this observational study, all patients admitted in our hospital with ALF due to hepatitis A virus infection during the period of 3 years from January 1st 2013 to December 31st 2015 were selected; 40 patients satisfied the inclusion and exclusion criteria. Detailed history taking, physical examination, haematological and biochemical investigations were performed. The day-to-day progress and treatment given until discharge or death were recorded. RESULTS Overall mortality in acute liver failure due to hepatitis A was 30%. Transplant free survival was 100% in patients with grade I and II encephalopathy, 66.6% in grade III encephalopathy and 22.2% in grade IV encephalopathy (P less than 0.001. Extrahepatic manifestations were observed in 29 patients (72.5%, the most common was thrombocytopenia in 22 patients (55% followed by acute kidney injury in 12 patients (30%. CONCLUSIONS The grade of hepatic encephalopathy was the single most important factor that determined the prognosis. Patients with grade I and II encephalopathy had 100% spontaneous survival rate.

  8. First case report of an acute genotype 3 hepatitis E infected pregnant woman living in South-Eastern France.

    Science.gov (United States)

    Anty, R; Ollier, L; Péron, J M; Nicand, E; Cannavo, I; Bongain, A; Giordanengo, V; Tran, A

    2012-05-01

    In European countries, epidemiology of hepatitis E virus (HEV) infection is not well known. Although, seroprevalence of HEV Immunoglobulin G reached a few percent in European women, no acute hepatitis E during pregnancy has been described so far. Here, we report a case of an autochthonous HEV genotype 3 infection in a 41-years-old pregnant woman living in a non-endemic country. The acute hepatitis had a spontaneous good outcome for the mother and the child. In non-endemic areas where Hepatitis E infections are emerging, unexplained cytolysis, whatever its level, in a pregnant woman could be investigated for HEV, using biological molecular and serology tools.

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

    Science.gov (United States)

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

    2014-07-01

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

  10. Benzodiazepine receptor antagonists for acute and chronic hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Kjaergard, L L; Gluud, C

    2001-01-01

    The pathogenesis of hepatic encephalopathy is unknown. It has been suggested that liver failure leads to the accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition which may progress to coma. Several trials have assessed benzodiazepine receptor...

  11. Amniotic fluid stem cells from EGFP transgenic mice attenuate hyperoxia-induced acute lung injury.

    Directory of Open Access Journals (Sweden)

    Shih-Tao Wen

    Full Text Available High concentrations of oxygen aggravate the severity of lung injury in patients requiring mechanical ventilation. Although mesenchymal stem cells have been shown to effectively attenuate various injured tissues, there is limited information regarding a role for amniotic fluid stem cells (AFSCs in treating acute lung injury. We hypothesized that intravenous delivery of AFSCs would attenuate lung injury in an experimental model of hyperoxia-induced lung injury. AFSCs were isolated from EGFP transgenic mice. The in vitro differentiation, surface markers, and migration of the AFSCs were assessed by specific staining, flow cytometry, and a co-culture system, respectively. The in vivo therapeutic potential of AFSCs was evaluated in a model of acute hyperoxia-induced lung injury in mice. The administration of AFSCs significantly reduced the hyperoxia-induced pulmonary inflammation, as reflected by significant reductions in lung wet/dry ratio, neutrophil counts, and the level of apoptosis, as well as reducing the levels of inflammatory cytokine (IL-1β, IL-6, and TNF-α and early-stage fibrosis in lung tissues. Moreover, EGFP-expressing AFSCs were detected and engrafted into a peripheral lung epithelial cell lineage by fluorescence microscopy and DAPI stain. Intravenous administration of AFSCs may offer a new therapeutic strategy for acute lung injury (ALI, for which efficient treatments are currently unavailable.

  12. Acute pancreatitis associated with pegylated interferon-alpha-2a therapy in chronic hepatitis C.

    Science.gov (United States)

    Choi, Jong Wook; Lee, June Sung; Paik, Woo Hyun; Song, Tae Jun; Kim, Jung Wook; Bae, Won Ki; Kim, Kyung-Ah; Kim, Jung Gon

    2016-03-01

    Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Combination therapy of pegylated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) is a current standard treatment for chronic HCV infection in Korea, which has considerable adverse effects. Acute pancreatitis is a rare complication of PEG-IFN-α administration. We report a case of a 62-year-old female who experienced acute pancreatitis after 4 weeks of PEG-IFN-α-2a and RBV combination therapy for chronic HCV infection. The main cause of the acute pancreatitis in this case was probably PEG-IFN-α rather than RBV for several reasons. A few cases have been reported in which acute pancreatitis occurred during treatment with PEG-IFN-α-2b. This is the first report of acute pancreatitis associated with PEG-IFN-α-2a in Korea.

  13. 17β-Estradiol administration attenuates seawater aspiration-induced acute lung injury in rats.

    Science.gov (United States)

    Fan, Qixin; Zhao, Pengtao; Li, Jiahuan; Xie, Xiaoyan; Xu, Min; Zhang, Yong; Mu, Deguang; Li, Wangping; Sun, Ruilin; Liu, Wei; Nan, Yandong; Zhang, Bo; Jin, Faguang; Li, Zhichao

    2011-12-01

    There is very little evidence on the value of administering estrogen in cases of seawater drowning which can induce acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Therefore, this study aimed to investigate whether 17β-estradiol (E2) treatment can attenuate seawater aspiration-induced ALI in rats. In the experiment, ALI was induced by endotracheal instillation of seawater (4mL/kg) and the rats were then given intraperitoneal injection of E2 (5mg/kg) 20min after seawater instillation. Finally, the changes of arterial blood gases which contained hydrogen ion concentration (pH), arterial oxygen tension (PaO(2)) and arterial carbon dioxide tension (PaCO(2)) were measured and the measurement of extravascular lung water (EVLW) was observed. The pulmonary histological changes were evaluated by hematoxylin-eosin stain. The expression of aquaporins (AQPs) 1, AQP5, and estrogen receptor-β (ERβ) was measured by western blotting and immunohistochemical methods. The results showed that compared with normal saline water, seawater aspiration induced more serious ALI in rats which was markedly alleviated by E2 treatment. Meanwhile, the ERβ in lung tissues was activated after E2 administration. The seawater aspiration group also presented with severe pulmonary edema which was paralleled with over expressed AQP1 and AQP5. However, the up-regulation of AQP1 and AQP5 was suppressed by the administration of E2, resulting in an attenuation of lung edema. In conclusion, E2 treatment could effectively attenuate seawater aspiration-induced acute lung injury in rats by the down-regulation of AQP1 and AQP5.

  14. Stent grafting of acute hepatic artery bleeding following pancreatic head resection

    Energy Technology Data Exchange (ETDEWEB)

    Stoupis, Christoforos [University of Berne, Inselspital, Department of Diagnostic, Interventional and Pediatric Radiology, Berne (Switzerland); Kreisspital, Radiology, Maennedorf (Switzerland); Ludwig, Karin; Triller, Juergen [University of Berne, Inselspital, Department of Diagnostic, Interventional and Pediatric Radiology, Berne (Switzerland); Inderbitzin, Daniel [University of Berne, Inselspital, Clinic for Visceral and Transplantation Surgery, Berne (Switzerland); Do, Dai-Do [University of Berne, Inselspital, Clinic for Angiology, Berne (Switzerland)

    2007-02-15

    The purpose of this study was to report the potential of hepatic artery stent grafting in cases of acute hemorrhage of the gastroduodenal artery stump following pancreatic head resection. Five consecutive male patients were treated because of acute, life-threatening massive bleeding. Instead of re-operation, emergency angiography, with the potential of endovascular treatment, was performed. Because of bleeding from the hepatic artery, a stent graft (with the over-the-wire or monorail technique) was implanted to control the hemmorhage by preserving patency of the artery. The outcome was evaluated. In all cases, the hepatic artery stent grafting was successfully performed, and the bleeding was immediately stopped. Clinically, immediately after the procedure, there was an obvious improvement in the general patient condition. There were no immediate procedure-related complications. Completion angiography (n=5) demonstrated control of the hemorrhage and patency of the hepatic artery and the stent graft. Although all patients recovered hemodynamically, three individuals died 2 to 10 days after the procedure. The remaining two patients survived, without the need for re-operation. Transluminal stent graft placement in the hepatic artery is a safe and technically feasible solution to control life-threatening bleeding of the gastroduodenal artery stump. (orig.)

  15. Glycolipid antigens for treating hepatic colorectal cancer metastases and their effect on the therapeutic efficacy of live attenuated Listeria monocytogenes.

    Science.gov (United States)

    Olino, Kelly; Edil, Barish H; Meckel, Kristen F; Pan, Xiaoyu; Thuluvath, Avesh; Pardoll, Drew M; Schulick, Richard D; Yoshimura, Kiyoshi; Weber, Walter P

    2012-05-01

    Previous work demonstrated that a subset of natural killer T cells in mice decreased the antitumor efficacy of live attenuated Listeria monocytogenes where the actin A and internalin B genes were genetically deleted (LMD) against murine hepatic colorectal cancer metastases. Therefore, we hypothesized that the use of specific glycolipids known to selectively stimulate natural killer T-cell subsets used alone or co-administered with LMD would increase survival. We found that early or multiple administrations of glycolipids after tumor challenge had a strong impact on survival with or without LMD. Solitary administration or treatment given later was less efficacious but still showed a strong trend toward enhancing the antitumor activity of LMD. These results underscore the potential of glycolipids in the treatment of hepatic metastases and encourage further investigations into the immunomodulation of natural killer T cells to enhance the antitumor activity of LMD.

  16. [Acute non-A non-B viral hepatitis].

    Science.gov (United States)

    Findor, J A; Lafage, M; Bruch Igartua, E M; Domecq, P; Firpo, A M; Domecq, R B

    1980-01-01

    Thirty-one patients HBs Ag negative seen between january 1978 and june 1980 were studied. Twenty-four of them were males and seven females. Their age ranged between 13 and 58 years. All of them were anti-HAV IgM negative. Six patients presented simultaneously Anti HBc and Anti HBs in the two first weeks of the illness. This fact could be imputed to an acquired immunity due to a previous infection with virus B. None of the patients studied had evidence of infectious mononucleosis or cytomegalovirus. In view of the absence of the markers of recent infection due to virus A and B these patients were considered to have a non A non B hepatitis. Twelve patients had evidence of previous hepatitis, thirteen had acquired the infection by parenteral route; four were post-transfusional and in six cases there was an epidemic medium. Forty-five percent of the patients studied had a biphasic elevation of the aminotransferases, and twenty percent had a cholestatic form. Two of the patients turned into a chronic active hepatitis and another one died of submasive necrosis; in both cases the via of infection was parenteral.

  17. Effects of acute hepatic and renal failure on pharmacokinetics of flunixin meglumine in rats.

    Science.gov (United States)

    Hwang, Youn-Hwan; Yun, Hyo-In

    2011-01-01

    The aim of this study was to investigate the effects of hepatic and renal failure on the pharmacokinetics of flunixin in carbon tetrachloride (CCl(4))- and glycerol-treated rats. After intravenous administration of flunixin (2 mg/kg), the plasma concentration of flunixin was measured by high-performance liquid chromatography. Both acute hepatic and renal failure resulted in significantly increased area under the curve (AUC), prolonged elimination half-life (t(1/2β)), and reduced total body clearance (Cl(tot)) compared with respective controls (Pflunixin.

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

    AIM: To asses the expression of myeloid dendritic cells (CD11c+) subset during acute HCV hepatitis and its possible involvement in natural history of the infection.METHODS: We enrolled 11 patients with acute hepatitis C (AHC) (Group A), 10 patients with acute hepatitis A (AHA) (as infective control-Group B) and 10 healthy donors (group C) in this study. All patients underwent selective flow cytometry gating strategies to assess the peripheral number of the myeloid dendritic cells (mDCs)to understand the possible role and differences during acute hepatitis.RESULTS: Eight of 11 patients with acute HCV hepatitis did not show any increase of mDCs compared to healthy individuals, while a significant decrease of mDCs was found in absolute cell count (z=-2.37; P<0.05) and percentage (z=-2.30; P<0.05) as compared with AHA.On the contrary, The remaining three patients of the group A had a higher mDCs number and percentage as occur in group B. Interestingly, after six months, those patients did not show any increase of mDCs subset were chronically infected. while the three subjects with an increase of peripheral mDCs, as in HAV acute infection,resolved the illness.CONCLUSION: The lack of increase of mDCs during acute hepatitis C might be an important factor involved in chronicization of the infection.

  19. Acute-onset chronic inflammatory demyelinating polyneuropathy in hantavirus and hepatitis B virus coinfection

    Science.gov (United States)

    Lim, Jong Youb; Lim, Young-Ho; Choi, Eun-Hi

    2016-01-01

    Abstract Introduction: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired autoimmune disorder with progressive weakness. Acute-onset CIDP resembles Guillain-Barre syndrome (GBS), a rapidly progressive disorder, and follows a chronic course. To our knowledge, no case of acute-onset CIDP in hantavirus and hepatitis B virus (HBV) coinfection has been reported previously. Clinical findings: We report a case of acute-onset CIDP that was initially diagnosed as GBS. Diagnoses: A 44-year-old male logger complained of acute quadriplegia and dyspnea. Mechanical ventilation was initiated. He was an HBV carrier with mild elevation of hepatic enzyme, and positive for hantavirus antibody. He was diagnosed with GBS and immunoglobulin therapy was administered. Interventions: After 8 months, quadriplegia and hypesthesia recurred. Immunoglobulin therapy at this time had no effect, but steroid therapy had some effect. Outcomes: A diagnosis of CIDP was made. After 2 months, severe extremity pain and dyspnea developed again, and steroid pulse therapy was initiated. Conclusion: Besides GBS, acute-onset CIDP can occur with hantavirus and HBV coinfection. Patients with this coinfection in whom GBS has been initially diagnosed should be followed up for a long time, because of the possibility of relapse or deterioration, and acute-onset CIDP should always be considered. PMID:27930572

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

    Directory of Open Access Journals (Sweden)

    Luciano Rezende Vilela

    2015-01-01

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

  1. Immune reconstitution inflammatory syndrome Kaposi sarcoma in the liver manifesting as acute obstructive hepatitis: another potential role for montelukast?

    Science.gov (United States)

    Read, P J; Lucas, S; Morris, S; Kulasegaram, R

    2013-02-01

    Immune reconstitution inflammatory syndrome has been described in Kaposi sarcoma, but does not usually manifest as acute hepatitis. We describe a case of rapid obstructive jaundice after initiation of antiretroviral therapy, in which the liver biopsy confirmed hepatic Kaposi sarcoma, and the clinical course was altered by the addition of montelukast.

  2. Clinical features of acute renal failure associated with hepatitis A virus infection.

    Science.gov (United States)

    Jung, Y J; Kim, W; Jeong, J B; Kim, B G; Lee, K L; Oh, K-H; Yoon, J-H; Lee, H-S; Kim, Y J

    2010-09-01

    Acute hepatitis A (AHA) is one of the most common infectious diseases; it is usually a self-limiting disease affecting the liver. Although extrahepatic manifestations are not common, some cases have been reported associated with acute renal failure. We reviewed the clinical features of patients with AHA complicated by acute renal failure (ARF group) and compared them with patients with noncomplicated AHA (non-ARF group). The medical records of 208 consecutive patients with AHA who were diagnosed between January 2003 and October 2008 were reviewed. We identified 15 patients (7.2%) with ARF associated with AHA. There were no differences between the ARF and non-ARF group with regard to gender and age. The peak value of alanine aminotransferase (ALT) (median: 6060 IU/L vs 1792 IU/L, P hepatic failure, and two patients died because of fulminant hepatic failure. There were no deaths among patients with noncomplicated AHA in the non-ARF group. Five patients underwent kidney biopsy; two patients were diagnosed with acute tubular necrosis, two patients with acute interstitial nephritis with IgA nephropathy and one patient with acute tubulointerstitial nephritis. All patients in the ARF group had microscopic haematuria and proteinuria (100%vs 31.1%, P < 0.001). Urine sodium levels were more than 10 mEq/L in 10 patients. The findings of high urinary sodium concentrations, microscopic haematuria and proteinuria did not support the diagnosis of hepatorenal syndrome (HRS). Patients with AHA with ARF had higher ALT levels, more prolonged PTs, and higher total bilirubin levels. The prognosis for these patients was poorer than for those without ARF. However, the patients with ARF and nonfulminant AHA had recovered with proper treatment and should not be confused with patients that have HRS.

  3. Acute cholestatic hepatitis caused by amoxicillin/clavulanate

    Science.gov (United States)

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

    2013-01-01

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

  4. Long-term ethanol exposure decreases the endotoxin-induced hepatic acute phase response in rats

    DEFF Research Database (Denmark)

    Glavind, Emilie; Vilstrup, Hendrik; Grønbaek, Henning

    2017-01-01

    -fed rats showed either no liver histopathological changes or varying degrees of steatosis. Ethanol feeding decreased the spontaneous liver mRNA expression of the prevailing acute phase protein alpha-2-macroglobulin by 30% (Ptumor necrosis factor...... an induced acute phase response is impaired in long-term ethanol-fed rats. METHODS: For six weeks, rats were either fed a Lieber-DeCarli ethanol-containing (36% as calories) liquid diet ad libitum or calorically pair-fed. Then, the rats were injected intraperitoneally with a low-dose of lipopolysaccharide...... (LPS) (0.5 mg/kg) to induce an acute phase response. Two hours after LPS, we measured the plasma concentrations of an array of inflammatory cytokines. Twenty-four hours after LPS, we measured the hepatic mRNA expression and serum concentrations of prominent rat acute phase proteins. RESULTS: Ethanol...

  5. The Clinical Course of Cirrhosis Patients Hospitalized for Acute Hepatic Deterioration: A Prospective Bicentric Study.

    Science.gov (United States)

    Shi, Yu; Yan, Huadong; Zhou, Zhibo; Fang, Hong; Li, Jiawei; Ye, Honghua; Sun, Wenjie; Zhou, Wenhong; Ye, Jingfen; Yang, Qiao; Yang, Ying; Hu, Yaoren; Chen, Zhi; Sheng, Jifang

    2015-11-01

    Patients with cirrhosis are vulnerable to acute hepatic insults and are more likely to develop rapid hepatic deterioration. The aim of this study is to describe the clinical course of patients with cirrhosis and hospitalized for acute hepatic deterioration (AHD).This is a prospective study involving 163 patients with cirrhosis and AHD. The occurrence of organ failures, systemic inflammatory response syndrome (SIRS), and infections during hospital stay were recorded and the relationship between organ failure and death or SIRS/infection was subsequently analyzed.Of 163 patients, 35 did not develop any organ failure during in-hospital follow-ups (90-day mortality: 0%); 84 had intrahepatic organ failures (IH-OFs, defined by liver and/or coagulation failure) (90-day mortality: 22.0%); and 44 patients developed extra-hepatic organ failures (EH-OFs, defined by kidney, cerebral, circulation, and respiratory failure) on the basis of IH-OF with a 90-day mortality of 90.9%. On multivariable analysis by a Cox proportion hazard model, age, WBC, presence of IH-OF, and EH-OF all predicted 90-day death. A logistic regression analysis identified SIRS being associated with the development of EH-OF. Furthermore, IH-OF at admission and infections occurred during the hospital stay were shown to be another 2 potential risk factors.The clinical course of cirrhosis patients with acute hepatic injury was characterized by 3 consecutive stages (AHD, IH-OF, and EH-OF), which provided a clear risk stratification. The PIRO criteria provided an accurate frame for prognostication of those patients. The systemic inflammatory response syndrome may be a target for blocking the progression to the EH-OF stage.

  6. Hepatic artery stent-grafts for the emergency treatment of acute bleeding

    Energy Technology Data Exchange (ETDEWEB)

    Bellemann, Nadine, E-mail: nadine.bellemann@med.uni-heidelberg.de [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, INF 110, 69120 Heidelberg (Germany); Sommer, Christof-Matthias; Mokry, Theresa; Kortes, Nikolas; Gnutzmann, Daniel; Gockner, Theresa; Schmitz, Anne [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, INF 110, 69120 Heidelberg (Germany); Weitz, Jürgen [Department of Surgery, University Hospital Heidelberg, INF 110, 69120 Heidelberg (Germany); Department for Visceral, Thoracic and Vascular Surgery at the University Hospital, Technical University Dresden (Germany); Kauczor, Hans-Ulrich; Radeleff, Boris; Stampfl, Ulrike [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, INF 110, 69120 Heidelberg (Germany)

    2014-10-15

    Highlights: • We report our experiences with stent-grafts for the treatment of acute hemorrhage from the hepatic artery or the stump of the gastroduodenal artery. • The technical success of stent-graft implantation was 88%. • The bleeding ceased immediately after stent-graft implantation in 88%. • The complication rate was 21%. - Abstract: Purpose: We evaluated the technical success and clinical efficacy of stent-graft implantation for the emergency management of acute hepatic artery bleeding. Methods: Between January 2010 and July 2013, 24 patients with hemorrhage from the hepatic artery were scheduled for emergency implantation of balloon expandable stent-grafts. The primary study endpoints were technical and clinical success, which were defined as successful stent-graft implantation with sealing of the bleeding site at the end of the procedure, and cessation of clinical signs of hemorrhage. The secondary study endpoints were complications during the procedure or at follow-up and 30-day mortality rate. Results: In 23 patients, hemorrhage occurred after surgery, and in one patient hemorrhage occurred after trauma. Eight patients had sentinel bleeding. In most patients (n = 16), one stent-graft was implanted. In six patients, two overlapping stent-grafts were implanted. The stent-grafts had a target diameter between 4 mm and 7 mm. Overall technical success was 88%. The bleeding ceased after stent-graft implantation in 21 patients (88%). The mean follow-up was 137 ± 383 days. In two patients, re-bleeding from the hepatic artery occurred during follow-up after 4 and 29 days, respectively, which could be successfully treated by endovascular therapy. The complication rate was 21% (minor complication rate 4%, major complication rate 17%). The 30-day mortality rate was 21%. Conclusions: Implantation of stent-grafts in the hepatic artery is an effective emergency therapy and has a good technical success rate for patients with acute arterial hemorrhage.

  7. Chronic Elevation of Liver Enzymes in Acute Intermittent Porphyria Initially Misdiagnosed as Autoimmune Hepatitis

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    A. González Estrada

    2011-01-01

    Full Text Available Autoimmune hepatitis is a disease characterized by an elevation of liver enzymes, as well as specific autoantibodies. It is more common in women than men. We describe a 32-year-old woman with elevated transaminases, autoantibodies, and a liver biopsy result suggestive of autoimmune hepatitis. The indicated treatment was administered without showing a satisfactory response. The patient had a family history of acute intermittent porphyria (AIP so we decided to begin treatment with hematin, achieving a complete remission of the symptoms. Acute intermittent porphyria is a rare condition characterized by neurovisceral symptoms, abdominal pain being the most common of them. The disease has a higher prevalence among young women and certain European countries such as Sweden, Great Britain, and Spain. A correct diagnosis and prompt treatment are essential because patients affected by AIP must have a strict followup due to the fatal outcome of the outbreaks.

  8. Tranilast reduces serum IL-6 and IL-13 and protects against thioacetamide-induced acute liver injury and hepatic encephalopathy.

    Science.gov (United States)

    Abdelaziz, Rania R; Elkashef, Wagdi F; Said, Eman

    2015-07-01

    Hepatic encephalopathy is a serious neuropsychiatric disorder usually affecting either acute or chronic hepatic failure patients. Hepatic encephalopathy was replicated in a validated rat model to assess the potential protective efficacy of tranilast against experimentally induced hepatic encephalopathy. Thioacetamide injection significantly impaired hepatic synthetic, metabolic and excretory functions with significant increase in serum NO, IL-6 and IL-13 levels and negative shift in the oxidant/antioxidant balance. Most importantly, there was a significant increase in serum ammonia levels with significant astrocytes' swelling and vacuolization; hallmarks of hepatic encephalopathy. Tranilast administration (300 mg/kg, orally) for 15 days significantly improved hepatic functions, restored oxidant/antioxidant balance, reduced serum NO, IL-6 and IL-13 levels. Meanwhile, serum ammonia significantly declined with significant reduction in astrocytes' swelling and vacuolization. Several mechanisms can be implicated in the observed hepato- and neuroprotective potentials of tranilast, such as its anti-inflammatory potential, its antioxidant potential as well as its immunomodulatory properties.

  9. Acute risk for hepatitis E virus infection among HIV-1-positive pregnant women in central Africa

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    Caron Mélanie

    2012-10-01

    Full Text Available Abstract Background Hepatitis E virus (HEV, an enterically transmitted pathogen, is highly endemic in several African countries. Pregnant women are at particularly high risk for acute or severe hepatitis E. In Gabon, a central African country, the prevalence of antibodies to HEV among pregnant women is 14.1%. Recent studies have demonstrated unusual patterns of hepatitis E (chronic hepatitis, cirrhosis among immunodeficient patients. Findings We investigated the prevalence of antibodies to HEV among pregnant women infected with HIV-1 or HTLV-1 in Gabon. Of 243 samples collected, 183 were positive for HIV-1 and 60 for HTLV-1; 16 women (6.6% had IgG antibodies to HEV. The seroprevalence was higher among HIV-1-infected women (7.1% than HTLV-1-infected women (5.0%. Moreover, the HIV-1 viral load was significantly increased (p ≤ 0.02 among women with past-HEV exposure (1.3E+05 vs 5.7E+04 copies per ml, whereas no difference was found in HTLV-1 proviral load (9.0E+01 vs 1.1E+03 copies per ml. Conclusions These data provide evidence that HIV-1-infected women are at risk for acute or severe infection if they are exposed to HEV during pregnancy, with an increased viral load.

  10. Isoforskolin pretreatment attenuates lipopolysaccharide-induced acute lung injury in animal models.

    Science.gov (United States)

    Yang, Weimin; Qiang, Dongjin; Zhang, Min; Ma, Limei; Zhang, Yonghui; Qing, Chen; Xu, Yunlong; Zhen, Chunlan; Liu, Jikai; Chen, Yan-Hua

    2011-06-01

    Isoforskolin was isolated from Coleus forskohlii native to Yunnan in China. We hypothesize that isoforskolin pretreatment attenuates acute lung injury induced by lipopolysaccharide (endotoxin). Three acute lung injury models were used: situ perfused rat lung, rat and mouse models of endotoxic shock. Additionally, lipopolysaccharide stimulated proinflammatory cytokine production was evaluated in human mononuclear leukocyte. In situ perfused rat lungs, pre-perfusion with isoforskolin (100, and 200 μM) and dexamethasone (65 μM, positive control) inhibited lipopolysaccharide (10 mg/L) induced increases in lung neutrophil adhesion rate, myeloperoxidase activity, lung weight Wet/Dry ratio, permeability-surface area product value, and tumor necrosis factor (TNF)-α levels. In rats, pretreatments with isoforskolin (5, 10, and 20 mg/kg, i.p.) and dexamethasone (5mg/kg, i.p.) markedly reduced lipopolysaccharide (6 mg/kg i.v.) induced increases of karyocyte, neutrophil counts and protein content in bronchoalveolar lavage fluid, and plasma myeloperoxidase activity. Lung histopathology showed that morphologic changes induced by lipopolysaccharide were less pronounced in the isoforskolin and dexamethasone pretreated rats. In mice, 5 mg/kg isoforskolin and dexamethasone caused 100% and 80% survival, respectively, after administration of lipopolysaccharide (62.5mg/kg, i.v., 40% survival if untreated). In human mononuclear leukocyte, isoforskolin (50, 100, and 200 μM) and dexamethasone (10 μM) pre-incubation lowered lipopolysaccharide (2 μg/mL) induced secretion of the cytokine TNF-α, and interleukins (IL)-1β, IL-6, and IL-8. In conclusion, pretreatment with isoforskolin attenuates lipopolysaccharide-induced acute lung injury in several models, and it is involved in down-regulation of inflammatory responses and proinflammatory cytokines TNF-α, IL-1β, IL-6, and IL-8.

  11. Coleus forskohlii extract attenuates the hypoglycemic effect of tolbutamide in vivo via a hepatic cytochrome P450-mediated mechanism.

    Science.gov (United States)

    Yokotani, Kaori; Chiba, Tsuyoshi; Sato, Yoko; Umegaki, Keizo

    2014-01-01

    This in vivo study in rats evaluated whether Coleus forskohlii extract (CFE) taken orally interacted with tolbutamide, a hypoglycemic drug metabolized by CYP2C enzymes. Rats were fed 0%, 0.3%, 1% (w/w) CFE diet for 2 weeks, followed by 0% CFE diet for 1 day. They were then given 40 mg/kg tolbutamide by intragastric gavage. Blood glucose level was determined up to 6 h after tolbutamide administration. CFE treatment increased total CYP content and various CYP subtypes in the liver. In particular, increases in activity and protein expression were noted for the CYP2B, CYP2C, and CYP3A subtypes. CFE treatment dose-dependently attenuated both the hypoglycemic action of tolbutamide at 6 h and the plasma concentration of tolbutamide. The activity of (S)-warfarin 7-hydroxylase, a CYP2C enzyme was negatively correlated with plasma tolbutamide level, which also showed a negative correlation with the reduction of blood glucose level. These results indicate that CFE induced hepatic CYPs in rats and attenuated the hypoglycemic action of tolbutamide via a hepatic CYP2C-mediated mechanism.

  12. Association between Plasma Fibrinogen Levels and Mortality in Acute-on-Chronic Hepatitis B Liver Failure

    OpenAIRE

    Zhexin Shao; Ying Zhao; Limin Feng; Guofang Feng; Juanwen Zhang; Jie Zhang

    2015-01-01

    Acute-on-chronic liver failure (AoCLF) is the most common type of liver failure and is associated with high mortality. Fibrinogen is critical in maintaining primary and secondary hemostasis. Therefore, we prospectively analyzed the association between fibrinogen and outcomes in AoCLF patients. Plasma fibrinogen was measured in 169 AoCLF, 173 chronic hepatitis B (CHB), and 171 healthy patients using a coagulation method. The predictive ability of fibrinogen for 3-month mortality in AoCLF patie...

  13. Acute Hepatitis after Ingestion of a Preparation of Chinese Skullcap and Black Catechu for Joint Pain

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    Charilaos Papafragkakis

    2016-01-01

    Full Text Available Many herbal preparations are routinely used and have been occasionally associated with a wide range of side effects, from mild to severe. Chinese skullcap and black catechu are herbal medications commonly used for their hepatoprotective and other properties. We report a case of acute toxic hepatitis associated with ingestion of Chinese skullcap and black catechu in one preparation for the alleviation of joint pain.

  14. Enhanced Surveillance for Acute and Likely Acute Hepatitis B in Canada: 1999 to 2002

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    David Boulos

    2005-01-01

    Full Text Available OBJECTIVE: To assess the incidence of clinically identified hepatitis B cases, as well as the demographic and risk behaviour profiles of these cases in a defined Canadian population.

  15. Epidemiological characteristics and clinical manifestations of acute non-A-E hepatitis

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    Delić Dragan

    2010-01-01

    Full Text Available Background/Aim. Acute non-A, non-B, non-C, non-D, non-E hepatitis (non-A-E AH is an acute disease of the liver of unknown etiology for which one or more new, so far undetected, hepatotropic viruses may be responsible. The frequency of non-A-E AH ranges from 3.8% to 33.9%, and therefore it has a significant place within current infectology and hepatology. The aim of our study was to establish the frequency, clinical and biochemical characteristics, natural course and outcome of non-A-E AH and compare them with control groups affected by acute viral hepatitis A, B and C. Methods. This descriptive-analytic prospective study included 31 patients with non-A-E AH treated at the Institute of Infectious and Tropical Diseases, Clinical Center of Serbia, Belgrade, from 2003 to 2008. They were followed up during the period not less than 6 months. The controls involved randomly selected patients, treated at the same time with a definite diagnosis of acute viral hepatitis A, B and C. Statistical data analysis used Mann-Whitney Utest, Student's t-test and variance analysis. The value of p < 0.05 was considered statistically significant. Results. The frequency of non-A-E AH was 7.6%. Almost no difference was found between sexes (male/female ratio was 1 : 1.07; it was developed in all age groups, with the highest incidence in the middle age (mean age was 38.32 ± 15.3 years. It appeared equally throughout the whole year. Out of risk factors, inoculation risk was predominant (before all, dental interventions, mostly involving urban population living in comfortable conditions. The duration of incubation varied much ranging from 20 to 180 days (median 60 days. By clinical course, moderate and icteric forms were most common, mostly corresponding to acute hepatitis A and C. On the other hand, by duration of the disease (mean duration was 67.1 ± 27.1 and chronic transformation, non-A-E AH resembled to acute hepatitis B. Progression to chronicity was recorded in 9

  16. Hepatitis C and recurrent treatment-resistant acute ischemic stroke

    OpenAIRE

    Saxsena, Aneeta; Tarsia, Joseph; Dunn, Casey; Aysenne, Aimee; Shah, Basil; Moore, David F.

    2013-01-01

    Since the introduction of recombinant tissue plasminogen activator and thrombolysis, acute ischemic stroke has become a treatable disorder if the patient presents within the 4.5-hour time window. Typically, sporadic stroke is caused by atherosclerotic disease involving large or small cerebral arteries or secondary to a cardioembolic source often associated with atrial fibrillation. In the over-65-year age group, more rare causes of stroke, such as antiphospholipid syndromes, are unusual; such...

  17. D-pinitol attenuates the impaired activities of hepatic key enzymes in carbohydrate metabolism of streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Sivakumar, Selvaraj; Subramanian, Sorimuthu P

    2009-09-01

    During diabetes mellitus, endogenous hepatic glucose production is increased as a result of impaired activities of the key enzymes of carbohydrate metabolism, which leads to the condition known as hyperglycemia. D-pinitol, a bioactive constituent isolated from soybeans, has been shown to reduce hyperglycemia in experimental diabetes. We therefore designed this study to investigate the effect of oral administration of D-pinitol (50 mg/kg b. w. for 30 days) on the activities of key enzymes in carbohydrate and glycogen metabolism in the liver tissues of streptozotocin-induced diabetic rats. The efficacy was compared with glyclazide, a standard hypoglycemic drug. Oral administration of D-pinitol to diabetic group of rats showed a marked decrease in the levels of blood glucose, glycosylated hemoglobin and an increase in plasma insulin and body weight. The activities of the hepatic enzymes such as hexokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase, glycogen synthase and hepatic glycogen content were significantly (p pinitol. The results suggest that alterations in the activities of key metabolic enzymes of carbohydrate metabolism could be one of the biochemical rationale by which D-pinitol attenuates the hyperglycemic effect in diabetic rats.

  18. Supplementation of parenteral nutrition with fish oil attenuates acute lung injury in a rat model

    Science.gov (United States)

    Kohama, Keisuke; Nakao, Atsunori; Terashima, Mariko; Aoyama-Ishikawa, Michiko; Shimizu, Takayuki; Harada, Daisuke; Nakayama, Mitsuo; Yamashita, Hayato; Fujiwara, Mayu; Kotani, Joji

    2014-01-01

    Fish oil rich in n-3 polyunsaturated fatty acids has diverse immunomodulatory properties and attenuates acute lung injury when administered in enternal nutrition. However, enteral nutrition is not always feasible. Therefore, we investigated the ability of parenteral nutrition supplemented with fish oil to ameliorate acute lung injury. Rats were infused with parenteral nutrition solutions (without lipids, with soybean oil, or with soybean oil and fish oil) for three days. Lipopolysaccharide (15 mg/kg) was then administered intratracheally to induce acute lung injury, characterized by impaired lung function, polymorphonuclear leukocyte recruitment, parenchymal tissue damage, and upregulation of mRNAs for inflammatory mediators. Administration of parenteral nutrition supplemented with fish oil prior to lung insult improved gas exchange and inhibited neutrophil recruitment and upregulation of mRNAs for inflammatory mediators. Parenteral nutrition supplemented with fish oil also prolonged survival. To investigate the underlying mechanisms, leukotriene B4 and leukotriene B5 secretion was measured in neutrophils from the peritoneal cavity. The neutrophils from rats treated with fish oil-rich parenteral nutrition released significantly more leukotriene B5, an anti-inflammatory eicosanoid, than neutrophils isolated from rats given standard parenteral nutrition. Parenteral nutrition with fish oil significantly reduced lipopolysaccharide-induced lung injury in rats in part by promoting the synthesis of anti-inflammatory eicosanoids. PMID:24688221

  19. Bone marrow and nonbone marrow Toll like receptor 4 regulate acute hepatic injury induced by endotoxemia.

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    Edith Hochhauser

    Full Text Available BACKGROUND: Toll-like receptors (TLRs are expressed in immune cells and hepatocytes. We examined whether hepatic Toll-like receptor 4 (TLR4 is involved in the acute hepatic injury caused by the administration of lipopolysaccharide (LPS (septic shock model. METHODS: Wild type (WT, TLR4-deficient and chimera mice underwent myeloablative bone marrow transplantation to dissociate between TLR4 expression in the liver or in the immune-hematopoietic system. Mice were injected with LPS and sacrificed 4 hours later. RESULTS: Compared to TLR4 deficient mice, WT mice challenged with LPS displayed increased serum liver enzymes and hepatic cellular inflammatory infiltrate together with increased serum and hepatic levels of interleukin 1β (IL-1β, tumor necrosis factor α (TNFα ,Up-regulation of hepatic mRNA encoding TLR4, IκB and c-jun expressions. TLR4 mutant mice transplanted with WT bone marrow were more protected than WT chimeric mice bearing TLR4 mutant hemopoietic cells from LPS, as seen by IL-1β and TNFα levels. We then used hepatocytes (Huh7 and macrophages from monocytic cell lines to detect TLR mRNA expression. Macrophages expressed a significantly higher level of TLR4 mRNA and TLR2 (more than 3000- and 8000-fold respectively compared with the hepatocyte cell line. LPS administration induced TLR4 activation in a hepatocyte cell line in a dose dependent manner while TLR2 mRNA hardly changed. CONCLUSIONS: These results suggest that TLR4 activation of hepatocytes participate in the immediate response to LPS induced hepatic injury. However, in this response, the contribution of TLR4 on bone marrow derived cells is more significant than those of the hepatocytes. The absence of the TLR4 gene plays a pivotal role in reducing hepatic LPS induced injury.

  20. Hepatitis E virus infection in patients with acute non-A, non-B, non-C hepatitis in Central Brazil

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    Nara Rubia de Freitas

    Full Text Available Hepatitis E virus (HEV infection has a worldwide distribution and represents an important cause of acute hepatitis. This study aims to investigate the occurrence of HEV infection and factors associated with this infection in patients with acute non-A, non-B, non-C hepatitis in Central Brazil. From April 2012 to October 2014, a cross-sectional study was conducted among 379 patients with acute non-A, non-B, non-C hepatitis in the City of Goiania, Central Brazil. Serum samples of all patients were tested for serological markers of HEV infection (anti-HEV IgM and IgG by ELISA. Positive samples were confirmed using immunoblot test. Anti-HEV IgM and IgG positive samples were tested for HEV RNA. Of the 379 serum samples, one (0.3% and 20 (5.3% were positive for anti-HEV IgM and IgG, respectively. HEV RNA was not found in any sample positive for IgM and/or IgG anti-HEV. After multivariate analysis, low education level was independently associated with HEV seropositivity (p = 0.005, as well as living in rural area, with a borderline p-value (p = 0.056. In conclusion, HEV may be responsible for sporadic self-limited cases of acute hepatitis in Central Brazil.

  1. Hepatitis E virus infection in patients with acute non-A, non-B, non-C hepatitis in Central Brazil

    Science.gov (United States)

    de Freitas, Nara Rubia; de Santana, Edna Braz Rocha; Silva, Ágabo Macedo da Costa e; da Silva, Sueli Meira; Teles, Sheila Araújo; Gardinali, Noemi Rovaris; Pinto, Marcelo Alves; Martins, Regina Maria Bringel

    2016-01-01

    Hepatitis E virus (HEV) infection has a worldwide distribution and represents an important cause of acute hepatitis. This study aims to investigate the occurrence of HEV infection and factors associated with this infection in patients with acute non-A, non-B, non-C hepatitis in Central Brazil. From April 2012 to October 2014, a cross-sectional study was conducted among 379 patients with acute non-A, non-B, non-C hepatitis in the City of Goiania, Central Brazil. Serum samples of all patients were tested for serological markers of HEV infection (anti-HEV IgM and IgG) by ELISA. Positive samples were confirmed using immunoblot test. Anti-HEV IgM and IgG positive samples were tested for HEV RNA. Of the 379 serum samples, one (0.3%) and 20 (5.3%) were positive for anti-HEV IgM and IgG, respectively. HEV RNA was not found in any sample positive for IgM and/or IgG anti-HEV. After multivariate analysis, low education level was independently associated with HEV seropositivity (p = 0.005), as well as living in rural area, with a borderline p-value (p = 0.056). In conclusion, HEV may be responsible for sporadic self-limited cases of acute hepatitis in Central Brazil. PMID:27759769

  2. Hepatic perfusion changes in an experimental model of acute pancreatitis: Evaluation by perfusion CT

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    Tutcu, Semra [Department of Surgery, Celal Bayar University, School of Medicine, Manisa (Turkey); Serter, Selim, E-mail: serterselim@gmail.co [Department of Radiology, Celal Bayar University, School of Medicine, Manisa (Turkey); Kaya, Yavuz; Kara, Eray [Department of Surgery, Celal Bayar University, School of Medicine, Manisa (Turkey); Nese, Nalan [Department of Pathology, Celal Bayar University, School of Medicine, Manisa (Turkey); Pekindil, Goekhan [Department of Radiology, Celal Bayar University, School of Medicine, Manisa (Turkey); Coskun, Teoman [Department of Surgery, Celal Bayar University, School of Medicine, Manisa (Turkey)

    2010-08-15

    Purpose: It is known that acute pancreatitis may cause secondary changes in several organs. Liver is one of these involved organs. In different experimental studies hepatic damages were shown histopathologically in acute pancreatitis but there are a few studies about perfusion disorders that accompany these histopathologic changes. Perfusion CT (pCT) provides the ability to detect regional and global alterations in organ blood flow. The purpose of the study was to describe hepatic perfusion changes in experimental acute pancreatitis model with pCT. Materials and methods: Forty Sprague-Dawley rats of both genders with average weights of 250 g were used. Rats were randomized into two groups. Twenty rats were in control group and 20 in acute pancreatitis group. pCT was performed. Perfusion maps were formed by processing the obtained images with perfusion CT software. Blood flow (BF) and blood volume (BV) values were obtained from these maps. All pancreatic and liver tissues were taken off with laparotomy and histopathologic investigation was performed. Student's t test was used for statistical analyses. Results: In pCT we found statistically significant increase in blood volume in both lobes of liver and in blood flow in right lobe of the liver (p < 0.01). Although blood flow in left lobe of the liver increased, it did not reach statistical significance. Conclusion: The quantitative analysis of liver parenchyma with pCT showed that acute pancreatitis causes a significant perfusion changes in the hepatic tissue. Systemic mediators seem to be effective as well as local inflammatory changes in perfusion changes.

  3. Severe acute cholestatic hepatitis of unknown etiology successfully treated with the Chinese herbal medicine Inchinko-to (TJ-135)

    Institute of Scientific and Technical Information of China (English)

    Susumu Ohwada; Isao Kobayashi; Nobuo Harasawa; Kyoichiro Tsuda; Yosikatsu Inui

    2009-01-01

    Severe acute hepatitis of unknown etiology is difficult to treat and often progresses to subacute fulminant hepatitis or late-onset hepatic failure. A 45-year-old wellnourished, healthy man had progressive fatigue and his liver function tests showed severe liver dysfunction. The etiology of sever acute cholestatic hepatitis was unknown. The liver function tests normalized gradually, which excluded high persistent total bilirubin after starting on predonine. A liver biopsy showed chronic active hepatitis with mild fibrosis (A2, F1). Oral Inchinko-to, a Chinese herbal medicine, at 7.5 g daily was prescribed. The treatment was effective with no adverse effects. We present a successfully treated case and discuss hepatoprotective and choleretic effects of Inchinko-to.

  4. Hepatic damage during acute pancreatitis in the rat

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    A.M.M. Coelho

    1997-08-01

    Full Text Available We studied the alterations in the metabolism of liver mitochondria in rats with acute pancreatitis. Male Wistar rats were allocated to a control group (group I and to five other groups corresponding to 2, 4, 12, 24 and 48 h after the induction of acute pancreatitis by the injection of 5% sodium taurocholate into the pancreatic duct. Sham-operated animals were submitted to the same surgical steps except for the induction of acute pancreatitis. Mitochondrial oxidation and phosphorylation were measured polarographically by determining oxygen consumption without ADP (basal respiration, state 4 and in the presence of ADP (activated respiration, state 3. Serum amylase, transaminases (ALT and AST and protein were also determined. Ascitic fluid, contents of amylase, trypsin and total protein were also determined and arterial blood pressure was measured in all groups. In ascitic fluid, trypsin and amylase increased reaching a maximum at 2 and 4 h, respectively. Serum amylase increased at 2 h reaching a maximum at 4 h. Serum transaminase levels increased at 12 and 24 h. After 2 h (and also 4 h there was an increase in state 4 respiration (45.65 ± 1.79 vs 28.96 ± 1.50 and a decrease in respiration control rate (3.53 ± 0.09 vs 4.45 ± 0.08 and in the ADP/O ratio (1.77 ± 0.02 vs 1.91 ± 0.01 compared to controls (P<0.05. These results indicate a disruption of mitochondrial function, which recovered after 12 h. In the 48-h groups there was mitochondrial damage similar to that occurring in ischemic lesion. Beat-to-beat analysis (30 min showed that arterial blood pressure remained normal up to 24 h (111 ± 3 mmHg while a significant decrease occurred in the 48-h group (91 ± 4 mmHg. These data suggest biphasic damage in mitochondrial function in acute pancreatitis: an initial uncoupled phase, possibly secondary to enzyme activity, followed by a temporary recovery and then a late and final dysfunction, associated with arterial hypotension, possibly related

  5. Micro-RNA-122 levels in acute liver failure and chronic hepatitis C.

    Science.gov (United States)

    Dubin, Perry H; Yuan, Hejun; Devine, Robert K; Hynan, Linda S; Jain, Mamta K; Lee, William M

    2014-09-01

    MicroRNA-122 (miR-122) is the foremost liver-related micro-RNA, but its role in the hepatocyte is not fully understood. To evaluate whether circulating levels of miR-122 are elevated in chronic-HCV for a reason other than hepatic injury, we compared serum level in patients with chronic hepatitis C to other forms of liver injury including patients with acute liver failure and healthy controls. MiR-122 was quantitated using sera from 35 acute liver failure patients (20 acetaminophen-induced, 15 other etiologies), 39 chronic-HCV patients and 12 controls. In parallel, human genomic DNA (hgDNA) levels were measured to reflect quantitatively the extent of hepatic necrosis. Additionally, six HIV-HCV co-infected patients, who achieved viral clearance after undergoing therapy with interferon and ribavirin, had serial sera miR-122 and hgDNA levels measured before and throughout treatment. Serum miR-122 levels were elevated approximately 100-fold in both acute liver failure and chronic-HCV sera as compared to controls (P < 0.001), whereas hgDNA levels were only elevated in acute liver failure patients as compared to both chronic-HCV and controls (P < 0.001). Subgroup analysis showed that chronic-HCV sera with normal aminotransferase levels showed elevated miR-122 despite low levels of hepatocyte necrosis. All successfully treated HCV patients showed a significant Log10 decrease in miR-122 levels ranging from 0.16 to 1.46, after sustained viral response. Chronic-HCV patients have very elevated serum miR-122 levels in the range of most patients with severe hepatic injury leading to acute liver failure. Eradication of HCV was associated with decreased miR-122 but not hgDNA. An additional mechanism besides hepatic injury may be active in chronic-HCV to explain the exaggerated circulating levels of miR-122 observed.

  6. Inhibition of soluble epoxide hydrolase attenuates hepatic fibrosis and endoplasmic reticulum stress induced by carbon tetrachloride in mice

    Science.gov (United States)

    Harris, Todd R.; Bettaieb, Ahmed; Kodani, Sean; Dong, Hua; Myers, Richard; Chiamvimonvat, Nipavan; Haj, Fawaz G.; Hammock, Bruce D.

    2015-01-01

    Liver fibrosis is a pathological condition in which chronic inflammation and changes to the extracellular matrix lead to alterations in hepatic tissue architecture and functional degradation of the liver. Inhibitors of the enzyme soluble epoxide hydrolase (sEH) reduce fibrosis in the heart, pancreas and kidney in several disease models. In this study, we assess the effect of sEH inhibition on the development of fibrosis in a carbon tetrachloride (CCl4)-induced mouse model by monitoring changes in the inflammatory response, matrix remolding and endoplasmic reticulum stress. The sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) was administered in drinking water. Collagen deposition in the liver was increased five-fold in the CCl4-treated group, and this was returned to control levels by TPPU treatment. Hepatic expression of Col1a2 and 3a1 mRNA was increased over fifteen-fold in the CCl4-treated group relative to the control group, and this increase was reduced by 50% by TPPU treatment. Endoplasmic reticulum (ER) stress observed in the livers of CCl4-treated animals was attenuated by TPPU treatment. In order to support the hypothesis that TPPU is acting to reduce the hepatic fibrosis and ER stress through its action as a sEH inhibitor we used a second sEH inhibitor, trans-4-{4-[3-(4-trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid (t-TUCB), and sEH null mice. Taken together, these data indicate that the sEH may play an important role in the development of hepatic fibrosis induced by CCl4, presumably by reducing endogenous fatty acid epoxide chemical mediators acting to reduce ER stress. PMID:25827057

  7. PREVALENCE OF DIFFERENT VIRAL MARKERS IN PATIENTS OF ACUTE VIRAL HEPATITIS IN AND AROUND VISAKHAPATNAM : HOSPITAL BASED STUDY

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    Aruna Sree

    2015-04-01

    Full Text Available Acute viral hepatitis (AVH is a major public health problem and is an important cause of morbidity and mortality in the developing countries. AIM: The aim of the present study is to study the serological profile of acute viral hepatitis in children and adults admitted in King George Hospital, Visakhapatnam and also age and sex distribution of patients suffering from acute viral hepatitis and also comparing the etiological profile by studying serological markers of common viral agents. SUBJECTS AND METHODS: Samples were collected from 80 individuals with jaundice and other clinical and biochemical evidences of acute viral hepatitis . They were tested for hepatitis surface antigen, HBcIgM, HAVIgM, HEVIgM, Antibodies to HCV by the enzyme - linked immuno sorbent assay. RESULTS: Out of the 80 viral hepatitis cases (47 adults+33 children. In adults 20(42.5% patients presented HBV (26.96% was identified as the most common cause of acute hepatitis followed by HEV14 (29.8%, HEV+HAV4 (8.5% and HAV 6(12.76%. Co - infections with more than one virus were present in 5cases; HAV - HEV co - infection being the most common. In children 16(48.5% presented with HAV, HAV+HEV11 (33.3%, HEV4 (12.12%, HBV1 (3.03% CONCLUSIONS: Vaccination of adults against hepatitis B is indicated, along with sexual education to decrease the incidence of hepatitis which is found as common etiological agent in adults. The incidence of HAV and HEV in children shows that there is need for improvement in sanitation and food habits.

  8. Effect of naked eukaryotic expression plasmid encoding rat augmenter of liver regeneration on acute hepatic injury and hepatic failure in rats

    Institute of Scientific and Technical Information of China (English)

    Li-Mei Zhang; Dian-Wu Liu; Jian-Bo Liu; Xiao-Lin Zhang; Xiao-Bo Wang; Long-Mei Tang; Li-Qin Wang

    2005-01-01

    AIM: To study the protective effect of eukaryotic expression plasmid encoding augmenter of liver regeneration (ALR) on acute hepatic injury and hepatic failure in rats. METHODS: The PCR-amplified ALR gene was recombined with pcDNA3 plasmid, and used to treat rats with acute hepatic injury. The rats with acute hepatic injury induced by intraperitoneal injection of 2 mL/kg 50% carbon tetrachloride (CCl4) were randomly divided into saline control group and recombinant pcDNA3-ALR plasmid treatment groups. Recombinant pcDNA3-ALR plasmid DNA (50 or 200 μg/kg) was injected into the rats with acute hepatic injury intravenously, intraperitoneally, or intravenously and intraperitoneally in combination 4 h after CCl4 administration, respectively. The recombinant plasmid was injected once per 12 h into all treatment groups four times, and the rats were decapitated 12 h after the last injection. Hepatic histopathological alterations were observed after HE staining, the expression of proliferating cell nuclear antigen (PCNA) in liver tissue was detected by immunohistochemical staining, and the level of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was determined by biochemical method. The recombinant plasmid DNA (200 μg/kg) and saline were intraperitoneally injected into the rats with acute hepatic failure induced by intraperitoneal injection of 4 mL/kg 50% CCl4 after 4 h of CCl4 administration, respectively. Rats living over 96 h were considered as survivals.RESULTS: The sequence of ALR cDNA of recombinant pcDNA3-ALR plasmid was accordant with the reported sequence of rat ALR cDNA. After the rats with acute hepatic injury were treated with recombinant pcDNA3-ALR plasmid, the degree of liver histopathological injury markedly decreased. The pathologic liver tissues, in which hepatic degeneration and necrosis of a small amount of hepatocytes and a large amount of infiltrating inflammatory cells were observed, and they became basically normal in the

  9. Risk factors and molecular characterization of acute sporadic symptomatic hepatitis E virus infection in Thailand

    Institute of Scientific and Technical Information of China (English)

    Kittiyod Poovorawan; Salyavit Jitmitrapab; Sombat Treeprasertsuk; Thanunrat Thongmee; Apiradee Theamboonlers; Pisit Tangkijvanich; Piyawat Komolmit; Yong Poovorawan

    2014-01-01

    Objective:To report clinical outcomes and viral genotypes of acute symptomatic hepatitis E virus (HEV) infection inThailand.Methods:Forty patients with acute symptomaticHEV infection were recruited during2009-2013.Clinical, demographic and laboratory data were collected.Diagnosis was accomplished by detection of anti-HEVIgM and/orHEVRNA in the serum or stool.HEV genotypes were classified by direct sequencing ofRT-PCRproducts and phylogenetic analysis. Results:The high risk group, comprising immune-compromised, liver cirrhosis and very elderly (>80 years) patients(17 cases), had higher levels of serum alkaline phosphatase at presentation compared with the low risk group.Two fatal cases resulted from acute hepatitisE in the high risk group.Initial clinical presentation did not show statistically significant differences.In six cases (6/40), the virus could be detected in serum or stool byRT-PCR and sequencing.Upon molecular characterization, the viruses were classified asHEV genotype3f and were in the same cluster as Thai swineHEV.Conclusions:Our data showed that acuteHEV infection has various clinical presentations and outcomes.Higher levels of serum alkaline phosphatase were observed in high risk patients.All isolated viruses were identified asHEV genotype3f possibly originating from swine.

  10. Acute overactive endocannabinoid signaling induces glucose intolerance, hepatic steatosis, and novel cannabinoid receptor 1 responsive genes.

    Directory of Open Access Journals (Sweden)

    Maxwell A Ruby

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

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

    Science.gov (United States)

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

    2015-09-01

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

  12. Molecular analysis of hepatitis A virus strains obtained from patients with acute hepatitis A in Mongolia, 2004-2013.

    Science.gov (United States)

    Tsatsralt-Od, Bira; Baasanjav, Nachin; Nyamkhuu, Dulmaa; Ohnishi, Hiroshi; Takahashi, Masaharu; Kobayashi, Tominari; Nagashima, Shigeo; Nishizawa, Tsutomu; Okamoto, Hiroaki

    2016-04-01

    Despite the high endemicity of hepatitis A virus (HAV) in Mongolia, the genetic information on those HAV strains is limited. Serum samples obtained from 935 patients with acute hepatitis in Ulaanbaatar, Mongolia during 2004-2013 were tested for the presence of HAV RNA using reverse transcription-PCR with primers targeting the VP1-2B region (481 nucleotides, primer sequences at both ends excluded). Overall, 180 patients (19.3%) had detectable HAV RNA. These 180 isolates shared 94.6-100% identity and formed four phylogenetic clusters within subgenotype IA. One or three representative HAV isolates from each cluster exhibited 2.6-3.9% difference between clusters over the entire genome. Cluster 1 accounted for 65.0% of the total, followed by Cluster 2 (30.6%), Cluster 3 (3.3%), and Cluster 4 (1.1%). Clusters 1 and 2 were predominant throughout the observation period, whereas Cluster 3 was undetectable in 2009 and 2013 and Cluster 4 became undetectable after 2009. The Mongolian HAV isolates were closest to those of Chinese or Japanese origin (97.7-98.5% identities over the entire genome), suggesting the evolution from a common ancestor with those circulating in China and Japan. Further molecular epidemiological analyses of HAV infection are necessary to investigate the factors underlying the spread of HAV and to implement appropriate prevention measures in Mongolia.

  13. Comparison of clinical features of acute hepatitis caused by hepatitis E virus (HEV) genotypes 3 and 4 in Sapporo, Japan.

    Science.gov (United States)

    Ohnishi, Sachiyo; Kang, Jong-Hon; Maekubo, Hiroshi; Arakawa, Tomohiro; Karino, Yoshiyasu; Toyota, Joji; Takahashi, Kazuaki; Mishiro, Shunji

    2006-12-01

    In Japan, indigenous acute hepatitis E is not a rare disease, and is mainly caused by hepatitis E virus (HEV) genotypes 3 and 4. Whether there is a difference in clinical features between the two genotypes remains unclear. This study compares the clinical features of patients infected with the two. From January, 1994, to December, 2003, 9 infected with HEV genotype 3 and 27 patients with genotype 4 were enrolled. Patients with genotype 4 had significantly higher peak alanine aminotransferase levels (median 3430IU/L, interquartile range 1747-4763 versus 1052IU/L, 845-2707; p=0.01). The lowest prothrombin time was lower in the genotype 4 group (61%, 42-77 versus 84%, 70-96; p=0.05). In our series, patients with genotype 4 had longer median duration of hospital stay (26.5 days, 18-31 versus 18 days, 12-23.5; p=0.06). The patients with genotype 4 infection tended to have more severe clinical manifestations than those with genotype 3 infection.

  14. Hepatitis A complicated with acute renal failure and high hepatocyte growth factor: A case report.

    Science.gov (United States)

    Oe, Shinji; Shibata, Michihiko; Miyagawa, Koichiro; Honma, Yuichi; Hiura, Masaaki; Abe, Shintaro; Harada, Masaru

    2015-08-28

    A 58-year-old man was admitted to our hospital. Laboratory data showed severe liver injury and that the patient was positive for immunoglobulin M anti-hepatitis A virus (HAV) antibodies. He was also complicated with severe renal dysfunction and had an extremely high level of serum hepatocyte growth factor (HGF). Therefore, he was diagnosed with severe acute liver failure with acute renal failure (ARF) caused by HAV infection. Prognosis was expected to be poor because of complications by ARF and high serum HGF. However, liver and renal functions both improved rapidly without intensive treatment, and he was subsequently discharged from our hospital on the 21(st) hospital day. Although complication with ARF and high levels of serum HGF are both important factors predicting poor prognosis in acute liver failure patients, the present case achieved a favorable outcome. Endogenous HGF might play an important role as a regenerative effector in injured livers and kidneys.

  15. Differential Gene Expression Profiles in Acute Hepatic Failure Model in Mice Infected with MHV-3 Virus Intervened by Anti-hepatic Failure Compound

    Institute of Scientific and Technical Information of China (English)

    HUANG Jiaquan; XIAO Fei; YU Haijing; HUANG Tiejun; HUANG Haiyan; NING Qin

    2007-01-01

    Differential gene expression profiles in Balb/cJ mouse model of acute hepatic failure in- fected with MHV-3 virus intervened by anti-hepatic failure compound (AHFC) and the changes of cytokines regulated by genes were investigated. The Balb/cj mice were divided into AHFC-intervened group and control group randomly. Acute hepatic failure model of Balb/cJ mice infected with MHV-3 virus was established. The survival rate in the two groups was observed. It was found that the survival rate in the AHFC-intervened group and control group was 90% and 50% re- spectively 48 h after intrapefitoneal injection of MHV-3 (P<0.05). Before and after the experiment, the cytokines in peripheral blood of the survival mice were determined, and RNA was extracted from survival mouse liver tissue for the analysis of the differential gene expression by a 36 kb mouse oli- gonuleotide DNA array. In all the genes of microarray there were 332 genes expressed differently in the two groups, in which 234 genes were up-regulated and 78 genes down-regulated. Through clustering analysis, the differential expression of immune related genes, including TNF receptor superfamily, Kctd9, Bcl-2, Fg12, IL-8, IL-6, IFN-γ, TNF-α etc. might be related with the curative effectiveness of AHFC. It was suggested that AHFC can balance the immune state of mouse model of acute hepatic failure infected with MHV-3 virus mainly through regulating the expression of immune related genes, decrease the immune damage and inhibit liver cell apoptosis of mouse acute hepatic failure model obviously so as to increase the survival rate of mouse models of acute hepatic failure.

  16. Burkholderia mallei CLH001 Attenuated Vaccine Strain Is Immunogenic and Protects against Acute Respiratory Glanders.

    Science.gov (United States)

    Hatcher, Christopher L; Mott, Tiffany M; Muruato, Laura A; Sbrana, Elena; Torres, Alfredo G

    2016-08-01

    Burkholderia mallei is the causative agent of glanders, an incapacitating disease with high mortality rates in respiratory cases. Its endemicity and ineffective treatment options emphasize its public health threat and highlight the need for a vaccine. Live attenuated vaccines are considered the most viable vaccine strategy for Burkholderia, but single-gene-deletion mutants have not provided complete protection. In this study, we constructed the select-agent-excluded B. mallei ΔtonB Δhcp1 (CLH001) vaccine strain and investigated its ability to protect against acute respiratory glanders. Here we show that CLH001 is attenuated, safe, and effective at protecting against lethal B. mallei challenge. Intranasal administration of CLH001 to BALB/c and NOD SCID gamma (NSG) mice resulted in complete survival without detectable colonization or abnormal organ histopathology. Additionally, BALB/c mice intranasally immunized with CLH001 in a prime/boost regimen were fully protected against lethal challenge with the B. mallei lux (CSM001) wild-type strain.

  17. Rabdosia japonica var. glaucocalyx Flavonoids Fraction Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Mice

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    Chun-jun Chu

    2014-01-01

    Full Text Available Rabdosia japonica var. glaucocalyx (Maxim. Hara, belonging to the Labiatae family, is widely used as an anti-inflammatory and antitumor drug for the treatment of different inflammations and cancers. Aim of the Study. To investigate therapeutic effects and possible mechanism of the flavonoids fraction of Rabdosia japonica var. glaucocalyx (Maxim. Hara (RJFs in acute lung injury (ALI mice induced by lipopolysaccharide (LPS. Materials and Methods. Mice were orally administrated with RJFs (6.4, 12.8, and 25.6 mg/kg per day for 7 days, consecutively, before LPS challenge. Lung specimens and the bronchoalveolar lavage fluid (BALF were isolated for histopathological examinations and biochemical analysis. The level of complement 3 (C3 in serum was quantified by a sandwich ELISA kit. Results. RJFs significantly attenuated LPS-induced ALI via reducing productions of the level of inflammatory mediators (TNF-α, IL-6, and IL-1β, and significantly reduced complement deposition with decreasing the level of C3 in serum, which was exhibited together with the lowered myeloperoxidase (MPO activity and nitric oxide (NO and protein concentration in BALF. Conclusions. RJFs significantly attenuate LPS-induced ALI via reducing productions of proinflammatory mediators, decreasing the level of complement, and reducing radicals.

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

    Science.gov (United States)

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

    2015-01-01

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

  19. The Impact of Acute Matriptase Inhibition in Hepatic Inflammatory Models

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    Judit Pomothy

    2016-01-01

    Full Text Available Purpose. Dysfunction of matriptase-2 can be involved in iron regulatory disorder via downregulation of hepcidin expression. In the present study, we investigated the effects of 3-amidinophenylalanine-derived matriptase inhibitors on porcine hepatic inflammatory cell models. Methods. Hepatocyte-Kupffer cell cocultures (ratio of 2 : 1 and 6 : 1 were treated with four structurally related matriptase inhibitors at 50 μM. Cell cytotoxicity and relative expressions of IL-6 and IL-8 and the levels of hepcidin were determined by MTS and porcine-specific ELISA. The extracellular H2O2 contents were analyzed by Amplex Red method. Results. Matriptase inhibitors at 50 µM for 24 h did not increase cell death rate. The elevated ROS production observed after short-term application of inhibitor MI-441 could be correlated with lowered hepcidin expression. MI-460 could significantly enhance hepcidin levels in the supernatants of cocultures (by 62.21±26.8% in hepatocyte-Kupffer cell, 2 : 1, and by 42.6±14.3% in hepatocyte-Kupffer cell, 6 : 1, cocultures, resp.. No significant changes were found in IL-6 and IL-8 levels in cocultures exposed to matriptase inhibitors. Conclusions. Based on in vitro findings, administration of MI-460 via modulation of hepcidin expression without cytotoxic and oxidative stress inducing properties might be a reliable alternative to treat iron overload in human and veterinary clinical practice.

  20. Case control study to identify risk factors for acute hepatitis C virus infection in Egypt

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    Kandeel Amr M

    2012-11-01

    Full Text Available Abstract Background Identification of risk factors of acute hepatitis C virus (HCV infection in Egypt is crucial to develop appropriate prevention strategies. Methods We conducted a case–control study, June 2007-September 2008, to investigate risk factors for acute HCV infection in Egypt among 86 patients and 287 age and gender matched controls identified in two infectious disease hospitals in Cairo and Alexandria. Case-patients were defined as: any patient with symptoms of acute hepatitis; lab tested positive for HCV antibodies and negative for HBsAg, HBc IgM, HAV IgM; and 7-fold increase in the upper limit of transaminase levels. Controls were selected from patients’ visitors with negative viral hepatitis markers. Subjects were interviewed about previous exposures within six months, including community-acquired and health-care associated practices. Results Case-patients were more likely than controls to have received injection with a reused syringe (OR=23.1, CI 4.7-153, to have been in prison (OR=21.5, CI 2.5-479.6, to have received IV fluids in a hospital (OR=13.8, CI 5.3-37.2, to have been an IV drug user (OR=12.1, CI 4.6-33.1, to have had minimal surgical procedures (OR=9.7, CI 4.2-22.4, to have received IV fluid as an outpatient (OR=8, CI 4–16.2, or to have been admitted to hospital (OR=7.9, CI 4.2-15 within the last 6 months. Multivariate analysis indicated that unsafe health facility practices are the main risk factors associated with transmission of HCV infection in Egypt. Conclusion In Egypt, focusing acute HCV prevention measures on health-care settings would have a beneficial impact.

  1. Hypothermia induced by adenosine 5'-monophosphate attenuates early stage injury in an acute gouty arthritis rat model.

    Science.gov (United States)

    Miao, Zhimin; Guo, Weiting; Lu, Shulai; Lv, Wenshan; Li, Changgui; Wang, Yangang; Zhao, Shihua; Yan, Shengli; Tao, Zhenyin; Wang, Yunlong

    2013-08-01

    To investigate whether the hypothermia induced by Adenosine 5'-Monophosphate (5'-AMP) could attenuate early stage injury in a rat acute gouty arthritis model. Ankle joint injection with monosodium urate monohydrate crystals (MSU crystals) in hypothermia rat model which was induced by 5'-AMP and then observe whether hypothermia induced by 5'-AMP could be effectively inhibit the inflammation on acute gouty arthritis in rats. AMP-induced hypothermia has protective effects on our acute gouty arthritis, which was demonstrated by the following criteria: (1) a significant reduction in the ankle swelling (p gouty arthritis model.

  2. Serum Hyperamylasemia as a prognostic indicator of acute viral hepatitis and cirrhosis of liver

    Directory of Open Access Journals (Sweden)

    N. Kaur

    2014-06-01

    Full Text Available Liver disease is a condition that causes liver inflammation or tissue damage and affects liver function. Liver functions tests are abnormal in various liver diseases such as hepatitis, cirrhosis and end stage liver disease. The study of pancreatic enzymes for prognostic purpose in evolving liver disease is gaining ground and act as prognostic indicator for liver diseases. Present study has been planned to assess the serum amylase status in 50 patients of acute viral hepatitis and 50 patients of cirrhosis of liver in comparison to 50 normal healthy control subjects. Levels of serum amylase were determined by CNP- G3 kinetic method. The serum levels of amylase were significantly raised (p<0.0001 in patients compared to control group and levels were observed to be constantly increased with increased severity of liver diseases. The probable cause of variation in serum amylase enzymes in acute viral hepatitis and cirrhosis of liver is its anatomical proximity and common egress system through Ampulla of vater into the duodenum.

  3. Ultrastructural changes in hepatic sinusoidal endothelial cells acutely exposed to colloidal iron.

    Science.gov (United States)

    Bassett, Mark L; Dahlstrom, Jane E; Taylor, Matthew C; Koina, Mark E; Maxwell, Lesley; Francis, Douglas; Jain, Sanjiv; McLean, Allan J

    2003-07-01

    Hepatic sinusoidal endothelial cells form an important interface between the vascular system, represented by the sinusoids, and the space of Disse that surrounds the hepatocyte microvilli. This study aimed to assess the light microscopic and ultrastructural effects of acute exposure of hepatic sinusoidal endothelial cells to colloidal iron by injection of rats with iron polymaltose. Eight minutes after a single intravenous injection of iron polymaltose sinusoidal endothelial cells showed defenestration, and thickening and layering as assessed by transmission electron microscopy. Kupffer cells and stellate cells appeared activated. These changes were not observed in control animals, experiments using equivalent doses of maltose, or experiments using colloidal carbon except for Kupffer cell activation due to colloidal carbon. No significant light microscopic changes were seen in study or control animals. The findings indicate that acute exposure to colloidal iron causes changes in hepatic sinusoidal endothelial cells, stellate cells and Kupffer cells. This may be the result of a direct toxic effect of iron or increased production of reactive oxygen species. These observations suggest a possible mechanism for defenestration of sinusoidal endothelial cells in ageing and in disease states.

  4. Inhibition of Hepatitis C Virus-Like Particle Binding to Target Cells by Antiviral Antibodies in Acute and Chronic Hepatitis C

    Science.gov (United States)

    Steinmann, Daniel; Barth, Heidi; Gissler, Bettina; Schürmann, Peter; Adah, Mohammed I.; Gerlach, J. Tilman; Pape, Gerd R.; Depla, Erik; Jacobs, Dirk; Maertens, Geert; Patel, Arvind H.; Inchauspé, Geneviève; Liang, T. Jake; Blum, Hubert E.; Baumert, Thomas F.

    2004-01-01

    Hepatitis C virus (HCV) is a leading cause of chronic viral hepatitis worldwide. The study of antibody-mediated virus neutralization has been hampered by the lack of an efficient and high-throughput cell culture system for the study of virus neutralization. The HCV structural proteins have been shown to assemble into noninfectious HCV-like particles (HCV-LPs). Similar to serum-derived virions, HCV-LPs bind and enter human hepatocytes and hepatoma cell lines. In this study, we developed an HCV-LP-based model system for a systematic functional analysis of antiviral antibodies from patients with acute or chronic hepatitis C. We demonstrate that cellular HCV-LP binding was specifically inhibited by antiviral antibodies from patients with acute or chronic hepatitis C in a dose-dependent manner. Using a library of homologous overlapping envelope peptides covering the entire HCV envelope, we identified an epitope in the N-terminal E2 region (SQKIQLVNTNGSWHI; amino acid positions 408 to 422) as one target of human antiviral antibodies inhibiting cellular particle binding. Using a large panel of serum samples from patients with acute and chronic hepatitis C, we demonstrated that the presence of antibodies with inhibition of binding activity was not associated with viral clearance. In conclusion, antibody-mediated inhibition of cellular HCV-LP binding represents a convenient system for the functional characterization of human anti-HCV antibodies, allowing the mapping of envelope neutralization epitopes targeted by naturally occurring antiviral antibodies. PMID:15308699

  5. Saturated hydrogen saline attenuates endotoxin-induced acute liver dysfunction in rats.

    Science.gov (United States)

    Xu, X-F; Zhang, J

    2013-01-01

    To determine the effect of saturated hydrogen saline on lipopolysaccharide (LPS)-induced acute liver dysfunction, rats were divided into control, LPS, and LPS plus saturated hydrogen saline (LPS+H(2)) groups. Treatment with saturated hydrogen saline prolonged the median survival time and reduced liver dysfunction. Moreover, saturated hydrogen saline significantly reduced pathological alterations in liver tissues, the number of ballooned hepatocytes, serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 levels, and myeloperoxidase (MPO) and malondialdehyde (MDA) levels in liver tissues (Phydrogen saline treatment. Saturated hydrogen saline also decreased phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated Jun kinase (p-JNK), nuclear factor-kappa B (NF-kappaB), and second mitochondria-derived activator of caspase (Smac) levels, and increased p38 activation (Phydrogen saline may attenuate LPS-induced acute liver dysfunction in rats, possibly by reducing inflammation and cell apoptosis. Mitogen-activated protein kinase (MAPK), NF-kappaB, and Smac may contribute to saturated hydrogen saline-mediated liver protection.

  6. Intrathecal PLC(β3) oligodeoxynucleotides antisense potentiates acute morphine efficacy and attenuates chronic morphine tolerance.

    Science.gov (United States)

    Quanhong, Zhou; Ying, Xue; Moxi, Chen; Tao, Xu; Jing, Wang; Xin, Zhang; Li, Wang; Derong, Cui; Xiaoli, Zhang; Wei, Jiang

    2012-09-07

    Morphine is a mainstay for chronic pain treatment, but its efficacy has been hampered by physical tolerance. The underlying mechanism for chronic morphine induced tolerance is complicated and not well understood. PLC(β3) is regarded as an important factor in the morphine tolerance signal pathway. In this study, we determined intrathecal (i.t.) administration of an antisense oligodeoxynucleotide (ODN) of PLC(β3) could quicken the on-set antinociceptive efficacy of acute morphine treatment and prolong the maximum effect up to 4h. The antisense could also attenuate the development of morphine-induced tolerance and left shift the ED50 after 7 day of coadministration with morphine. These results probably were contributed by the PLC(β3) antisense ODN as they successfully knocked down protein expression levels and reduced activity of PLC(β3) in spinal cord in rats. The mismatch group had no such effects. The results confirmed the important involvement of PLC(β3) in both acute morphine efficacy and chronic morphine tolerance at spinal level in rats. This study may provide an idea for producing a novel adjuvant for morphine treatment.

  7. Salvianolic Acid B Attenuates Rat Hepatic Fibrosis via Downregulating Angiotensin II Signaling

    Science.gov (United States)

    Li, Shu; Wang, Lina; Yan, Xiuchuan; Wang, Qinglan; Tao, Yanyan; Li, Junxia; Peng, Yuan; Liu, Ping; Liu, Chenghai

    2012-01-01

    The renin-angiotensin system (RAS) plays an important role in hepatic fibrosis. Salvianolic acid B (Sal B), one of the water-soluble components from Radix Salviae miltiorrhizae, has been used to treat hepatic fibrosis, but it is still not clear whether the effect of Sal B is related to angiotensin II (Ang II) signaling pathway. In the present study, we studied Sal B effect on rat liver fibrosis and Ang-II related signaling mediators in dimethylnitrosamine-(DMN-) induced rat fibrotic model in vivo and Ang-II stimulated hepatic stellate cells (HSCs) in vitro, with perindopril or losartan as control drug, respectively. The results showed that Sal B and perindopril inhibited rat hepatic fibrosis and reduced expression of Ang II receptor type 1 (AT1R) and ERK activation in fibrotic liver. Sal B and losartan also inhibited Ang II-stimulated HSC activation including cell proliferation and expression of type I collagen I (Col-I) and α-smooth muscle actin (α-SMA) production in vitro, reduced the gene expression of transforming growth factor beta (TGF-β), and downregulated AT1R expression and ERK and c-Jun phosphorylation. In conclusion, our results indicate that Sal B may exert an antihepatic fibrosis effect via downregulating Ang II signaling in HSC activation. PMID:23243430

  8. Salvianolic Acid B Attenuates Rat Hepatic Fibrosis via Downregulating Angiotensin II Signaling

    Directory of Open Access Journals (Sweden)

    Shu Li

    2012-01-01

    Full Text Available The renin-angiotensin system (RAS plays an important role in hepatic fibrosis. Salvianolic acid B (Sal B, one of the water-soluble components from Radix Salviae miltiorrhizae, has been used to treat hepatic fibrosis, but it is still not clear whether the effect of Sal B is related to angiotensin II (Ang II signaling pathway. In the present study, we studied Sal B effect on rat liver fibrosis and Ang-II related signaling mediators in dimethylnitrosamine-(DMN- induced rat fibrotic model in vivo and Ang-II stimulated hepatic stellate cells (HSCs in vitro, with perindopril or losartan as control drug, respectively. The results showed that Sal B and perindopril inhibited rat hepatic fibrosis and reduced expression of Ang II receptor type 1 (AT1R and ERK activation in fibrotic liver. Sal B and losartan also inhibited Ang II-stimulated HSC activation including cell proliferation and expression of type I collagen I (Col-I and α-smooth muscle actin (α-SMA production in vitro, reduced the gene expression of transforming growth factor beta (TGF-β, and downregulated AT1R expression and ERK and c-Jun phosphorylation. In conclusion, our results indicate that Sal B may exert an antihepatic fibrosis effect via downregulating Ang II signaling in HSC activation.

  9. Antioxidants vitamin E and C attenuate hepatic fibrosis in biliary-obstructed rats

    Institute of Scientific and Technical Information of China (English)

    Ali Riza Soylu; Huseyin Baloglu; Mevlut Ture; Kemal Kutlu; Kadir Kaymak; Nurettin Aydogdu; Umit Nusret Basaran; Semsi Altaner; Orhan Tarcin; Nursal Gedik; Hasan Umit; Ahmet Tezel; Gulbin Dokmeci

    2006-01-01

    AIM:To investigate whether antioxidants vitamin E and C can retard development of hepatic fibrosis in the biliary-obstructed rats.METHODS: Fifty Wistar albino rats were randomly assigned to 5 groups (10 rats in each). Bile duct was ligated in 40 rats and they were treated as follows: group vitC, vitamin C 10 rog/kg sc daily; group vitE, vitamin E 15 mg/kg sc daily; group vitEC, both of the vitamins; bile duct-ligated (BDL, control) group, physiological saline sc. The fifth group was assigned to sham operation. At the end of fourth week, the rats were decapitated, and hepatic tissue biochemical collagen content and collagen surface area were measured. Hepatic tissue specimens were histopathologically evaluated according to Scheuer system. Serum hyaluronate levels were measured by ELTSA method.RESULTS: Despite being higher than sham group, hepatic collagen level was significantly decreased in each of the vitC, vitE and vitEC groups (32.7 ± 1.2, 33.8 ±2.9, 36.7 ± 0.5 μg collagen/mg protein, respectively)compared to BDL (48.3 ± 0.6 mg collagen/g protein) (P< 0.001 for each vitamin group). Each isolated vitamin C, isolated vitamin E and combined vitamin E/C supplementation prevented the increase in hepatic collagen surface density (7.0% ± 1.1%, 6.2% ± 1.7%, 12.3% ±2.0%, respectively) compared to BDL (17.4% ± 5.6%) (P< 0.05 for each). The same beneficial effect of vitamin C,vitamin E and combined vitamin E/C treatment was also observed on the decrease of serum hyaluronate levels compared to BDL group (P < 0.001). The relative liver and spleen weights, serum transaminases, cholestatic enzymes, bilirubins and histopathological inflammation scores were not different between the antioxidant treatment groups and the control. However, fibrosis staging scores were obviously reduced only in the vitamin E/C combination group (vit EC: 2.4 ± 0.8 vs BDL: 3.1 ± 0.7;P < 0.05).CONCLUSION: Each antioxidant vitamin E, vitamin C and their combination retard hepatic

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

    Directory of Open Access Journals (Sweden)

    Jiying Jiang

    2013-08-01

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

  11. Infección aguda por el VHC Acute hepatitis C virus infection

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    A. Martínez Echeverría

    2004-01-01

    Full Text Available La infección aguda por el virus C de la hepatitis produce un cuadro clínico y bioquímico no específico e indistinguible de los causados por otros virus hepatotropos. El diagnóstico específico de la hepatitis aguda por virus C se basa en la detección en sangre del RNA-VHC mediante una técnica de reacción en cadena de la polimerasa cuyo resultado será positivo a partir de 1-2 semanas tras el contacto inicial con el virus. Los anticuerpos frente al VHC se detectan más tardíamente (a las 7-8 semanas por término medio no siendo útiles, como determinación aislada, para distinguir infección aguda de infección crónica o aclaramiento del virus (espontáneo o tras tratamiento. El 55-85% de los pacientes con infección aguda por el VHC no aclaran el virus y desarrollan una infección crónica con riesgo de evolución a cirrosis y de desarrollo de hepatocarcinoma. Por ello, la tendencia actual es tratar con interferón a todos aquellos pacientes en los que el RNA-VHC se mantenga positivo más allá de 3-4 meses tras el diagnóstico de la infección aguda.Acute hepatitis C virus infection produces clinical and biochemical features that is non-specific and indistinguishable from those caused by other hepatotropic viruses. The specific diagnosis of acute hepatitis C virus infection is based on the detection of serum RNA-HCV through a technique of PCR whose result will be positive after 1-2 weeks of the initial contact with the virus. The anti-bodies against HCV are detected later (after 7-8 weeks on average, and are not useful, as an isolated determination, in distinguishing acute infection from chronic infection or in clearing the virus (spontaneous or following treatment. Fifty-five to eighty-five percent of patients with acute HCV infection do not clear the virus and develop a chronic infection with risk of evolution to cirrhosis and of developing hepatocellular carcinoma. For this reason, the present tendency is to treat with interferon

  12. Effect of gomisin A in the prevention of acute hepatic failure induction.

    Science.gov (United States)

    Mizoguchi, Y; Kawada, N; Ichikawa, Y; Tsutsui, H

    1991-08-01

    Nearly all rats develop massive hepatic cell necrosis and die upon intravenous administration of heat-killed Propionibacterium acnes followed by a small amount of Gram-negative lipopolysaccharide 7 days later. However, when such an experimental liver disorder is induced in rats raised for 4 or more weeks on food containing 0.06% of gomisin A extracted and purified from Schizandra chinensis, the survival rate rises, histological changes of the liver improve remarkably, and splenocyte reactivity to phytohemagglutinin and pokeweed mitogen as well as splenocyte interleukin 1 productivity are retained. These results suggested the possibility that the development of acute hepatic failure may be prevented with the oral administration of gomisin A.

  13. Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH) presenting with acute fulminant hepatic failure.

    Science.gov (United States)

    Mhanni, A A; Chan, A; Collison, M; Seifert, B; Lehotay, D C; Sokoro, Ah; Huynh, H Q; Greenberg, C R

    2008-03-01

    We report on two Aboriginal patients with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. Both presented with acute hepatic failure with severe hypertransaminasemia and coagulopathy, prompting evaluation for emergent liver transplantation. The diagnosis of HHH syndrome was based on the presence of typical metabolic abnormalities. A protein-restricted diet and L-arginine or L-citrulline supplementation were immediately started, with rapid normalization of liver function test results and other biochemical abnormalities. Molecular analysis of the SLC25A15 gene showed that the two patients were homozygous for the common French Canadian mutation (F188Delta). The diagnosis of HHH syndrome should be considered in patients with unexplained fulminant hepatic failure. There does not appear to be a genotype-phenotype correlation for this presentation, inasmuch as the only other reported patient presenting with this picture had two different point mutations. Early identification and prompt treatment of these patients is crucial to avoid liver transplantation and can be life saving.

  14. Protective effects of protostemonine on LPS/GalN-induced acute liver failure: Roles of increased hepatic expression of heme oxygenase-1.

    Science.gov (United States)

    Cheng, Zhuo; Yue, Ling; Zhao, Wenhao; Yang, Xinzhou; Shu, Guangwen

    2015-12-01

    Here, we explored protective effects of protostemonine (PSN), on mouse acute liver failure induced by lipopolysaccharide/d-galactosamine (LPS/GalN). PSN dose-dependently declined LPS/GalN-induced lethality of mice as well as increase of ALT/AST activities in their serum. Hepatoprotective effects of PSN were also supported by liver histopathological examinations. After LPS/GalN treatment, severe oxidative stresses in the liver could be detected by boosted MDA and ROS as well as decreased GSH. Moreover, hepatic expression of pro-inflammatory cytokines, including TNF-α, IL-1β and IL-6, were sharply elevated. These symptoms were dose-dependently ameliorated by PSN. Mechanistically, PSN promoted the transcription and translation of heme oxygenase-1 (HO-1) in hepatocytes and liver Kupffer cells. Nrf2 is a master transcription factor contributing to the expression of HO-1. PSN elevated Nrf2 nuclear accumulation and enhanced Nrf2/HO-1 promoter interaction. Suppressing enzyme activity of HO-1 by co-treating mice with HO-1 inhibitor ZnPP abolished protective effects of PSN. ZnPP also abrogated alleviative impacts of PSN on LPS/GalN-mediated hepatic oxidative stresses and inflammatory responses. Finally, we showed that PSN exhibited undetectable toxic effects on vital organs of mice. Our findings suggested that PSN is able to attenuate LPS/GalN-induced acute liver failure and upregulating HO-1 expression is implicated in its hepatoprotective activity.

  15. Acute hepatitis C infection in HIV-negative men who have sex with men.

    Science.gov (United States)

    McFaul, K; Maghlaoui, A; Nzuruba, M; Farnworth, S; Foxton, M; Anderson, M; Nelson, M; Devitt, E

    2015-06-01

    Acute hepatitis C infection is recognized in HIV-infected men who have sex with men (MSM), but the risk in HIV-negative MSM remains unclear. We evaluated a population of MSM with acute hepatitis C. From January 2010 to May 2014, all cases of HCV antibody positive HIV-negative MSM were identified. European AIDS Network criteria were applied to determine acute infection, and 44 individuals fulfilled the criteria for acute hepatitis C. Ten were RNA negative at baseline and classed as prior spontaneous clearance. 15 (34.1%) had a previously negative HCV antibody within 1 year. 11 (25.0%) had significant elevation in ALT levels, and 18 (40.9%) were clinically diagnosed from risk exposure and history. Median age was 37 years (range 24-75). 41 (93.2%) individuals reported unprotected anal sex, 36 with (87.8%) both insertive and receptive intercourse, 4 (9.8%) with receptive intercourse, 1 (2.4%) with insertive intercourse, and no data were recorded for 3 (7.3%) patients. Individuals had an average of 7.3 reported (median 2, range 1-100) partners. 12 (27.3%) engaged in group sex, 11 (25.0%) practised fisting, 11 (25.0%) admitted using drugs during sexual activity, 16 (36.4%) reported nasal, and 9 (20.5%) reported injection drug use. 14 (31.8)% had unprotected sex whilst under the influence of recreational drugs. 29 individuals were aware of a partner's status. 2 (4.5%) individuals had sexual contact with a known HCV monoinfected partner, 13 (29.5%) with a HIV monoinfected partner and 6 (13.6%) with a HCV/HIV coinfected partner. 9 (20.5%) reported a partner/partners with no known infection. No data were available in 14 (31.8%) individuals. 13 (29.5%) individuals had a coexisting STI at the time of acute HCV diagnosis. 8 (18.2%) received HIV postexposure prophylaxis (PEP) within the 6 months prior to the HCV diagnosis (2 were participants in a HIV pre-exposure prophylaxis trial). 15 (34.1%) individuals achieved spontaneous clearance of HCV, and 11 patients received HCV

  16. Hydrogen-rich saline attenuates acute renal injury in sodium taurocholate-induced severe acute pancreatitis by inhibiting ROS and NF-κB pathway.

    Science.gov (United States)

    Shi, Qiao; Liao, Kang-Shu; Zhao, Kai-Liang; Wang, Wei-Xing; Zuo, Teng; Deng, Wen-Hong; Chen, Chen; Yu, Jia; Guo, Wen-Yi; He, Xiao-Bo; Abliz, Ablikim; Wang, Peng; Zhao, Liang

    2015-01-01

    Hydrogen (H2), a new antioxidant, was reported to reduce (•)OH and ONOO(-) selectively and inhibit certain proinflammatory mediators to product, without disturbing metabolic redox reactions or ROS involved in cell signaling. We herein aim to explore its protective effects on acute renal injury in sodium taurocholate-induced acute pancreatitis and its possible mechanisms. Rats were injected with hydrogen-rich saline (HRS group) or normal saline (SO and SAP group) through tail intravenously (6 mL/kg) and compensated subcutaneously (20 mL/kg) after successful modeling. Results showed that hydrogen-rich saline attenuated the following: (1) serum Cr and BUN, (2) pancreatic and renal pathological injuries, (3) renal MDA, (4) renal MPO, (5) serum IL-1β, IL-6, and renal TNF-α, HMGB1, and (6) tyrosine nitration, IκB degradation, and NF-κB activation in renal tissues. In addition, it increased the level of IL-10 and SOD activity in renal tissues. These results proved that hydrogen-rich saline attenuates acute renal injury in sodium taurocholate-induced acute pancreatitis, presumably because of its detoxification activity against excessive ROS, and inhibits the activation of NF-κB by affecting IκB nitration and degradation. Our findings highlight the potential value of hydrogen-rich saline as a new therapeutic method on acute renal injury in severe acute pancreatitis clinically.

  17. Predictors of the outcomes of acute-on-chronic hepatitis B liver failure

    Institute of Scientific and Technical Information of China (English)

    Hsiu-Lung Fan; Po-Sheng Yang; Hui-Wei Chen; Teng-Wei Chen; De-Chuan Chan; Chi-Hong Chu; Jyh-Cherng Yu

    2012-01-01

    AIM:TO identify the risk factors in predicting the outcome of acute-on-chronic hepatitis B liver failure patients.METHODS:We retrospectively divided 113 patients with acute-on-chronic liver failure-hepatitis B virus (ACLF-HBV) and without concurrent hepatitis C or D virus infection and hepatocellular carcinoma into two groups according to their outcomes after anti-HBV therapy.Their demographic,clinical,and biochemical data on the day of diagnosis and after the first week of treatment were analyzed using the Mann-Whitney U test,Fisher's exact test,and a multiple logistic regression analysis.RESULTS:The study included 113 patients (87 men and 26 women) with a mean age of 49.84 years.Fiftytwo patients survived,and 61 patients died.Liver failure (85.2%),sepsis (34.4%),and multiple organ failure (39.3%) were the main causes of death.Multivariate analyses showed that Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ scores ≥ 12[odds ratio (OR) =7.160,95% CI:2.834-18.092,P <0.001] and positive blood culture (OR =13.520,95%CI:2.740-66.721,P =0.001) on the day of diagnosis and model for end-stage liver disease (MELD) scores ≥ 28 (OR =8.182,95% CI:1.884-35.527,P =0.005)after the first week of treatment were independent predictors of mortality.CONCLUSION:APACHE Ⅱ scores on the day of diagnosis and MELD scores after the first week of anti-HBV therapy are feasible predictors of outcome in ACLF-HBV patients.

  18. Bamboo salt attenuates CCl4-induced hepatic damage in Sprague-Dawley rats.

    Science.gov (United States)

    Zhao, Xin; Song, Jia-Le; Kil, Jeung-Ha; Park, Kun-Young

    2013-08-01

    Bamboo salt, a Korean folk medicine, is prepared with solar salt (sea salt) and baked several times at high temperatures in a bamboo case. In this study, we compared the preventive effects of bamboo salt and purified and solar salts on hepatic damage induced by carbon tetrachloride in Sprague-Dawley rats. Compared with purified and solar salts, bamboo salts prevented hepatic damage in rats, as evidenced by significantly reduced serum levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase (P Bamboo salt (baked 9×) triggered the greatest reduction in these enzyme levels. In addition, it also reduced the levels of the proinflammatory cytokines interleukin (IL)-6, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α. Histopathological sections of liver tissue demonstrated the protective effect of bamboo salt, whereas sections from animals treated with the other salt groups showed a greater degree of necrosis. We also performed reverse transcription-polymerase chain reaction and western blot analyses of the inflammation-related genes iNOS, COX-2, TNF-α, and IL-1β in rat liver tissues. Bamboo salt induced a significant decrease (~80%) in mRNA and protein expression levels of COX-2, iNOS, TNF-α, and IL-1β, compared with the other salts. Thus, we found that baked bamboo salt preparations could prevent CCl4-induced hepatic damage in vivo.

  19. Dexamethasone pretreatment attenuates lung and kidney injury in cholestatic rats induced by hepatic ischemia/reperfusion.

    Science.gov (United States)

    Zhou, Liangyi; Yao, Xiangqing; Chen, Yanling

    2012-02-01

    Hepatic ischemia followed by reperfusion (IR) results in mild to severe organ injury, in which tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) seem to be involved. Thus, we aim to assess the influence of hepatic ischemia/reperfusion injury on remote organs in addition to cholestasis and consider the possible efficacy of steroid pretreatment in reducing the injury. A common bile duct ligation model was done on 24 male Sprague-Dawley rats. After 7 days, the rats were divided randomly into control group, IR group, and dexamethasone (DEX) group. The IR group showed significant increases in serum alanine aminotransferase, aspartate aminotransferase, and creatinine levels compared with the control and DEX groups. By ELISA techniques, higher levels of TNF-α and IL-1β in lung and kidney tissues were measured in the IR group than in the control and DEX groups, these were verified by immunohistochemistry. The lung histology of the IR group rats showed neutrophil infiltration, interstitial edema, and alveolar wall thickening. Kidney histology of the IR group rats showed vacuolization of the proximal tubular epithelial cells and tubular dilatation with granular eosinophilic casts. Better morphological aspects were observed in the DEX-pretreated animals. Minimal lesions were observed in the control. The results suggest that hepatic ischemia/reperfusion injury in cholestatic rats induced lung and kidney injuries. Pretreatment with dexamethasone reduced the IR-induced injury in addition to cholestasis.

  20. Efficacy of immunization against hepatitis B virus infection in acute leukemia

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    Tuphan Kanti Dolai

    2010-09-01

    Full Text Available Objective: The aim of this study was to assess the antibody response to combined passive-active immunization versus active immunization against hepatitis B in 71 patients with acute leukemia with negative hepatitis B virus serology at presentation. Materials and Methods: The first group (n=28 received a double dose of hepatitis B vaccine at 0, 1, 2 and 6 months and immunoglobin (HBIG at 0 and 1 month concurrently with vaccine but at a different intramuscular site. The second group (n=43 received double dose of hepatitis B vaccine at 0, 1, 2, and 6 months. HBsAg and anti-HBs titers were determined one month after the 1st, 2nd, 3rd and 4th doses of vaccine. Results: In the vaccine-only group, 2.56%, 8.33%, 14.28% and 34.29% of patients developed anti-HBs titer ≥10 IU/L after the 1st, 2nd, 3rd and 4th doses of vaccine, respectively. In the HBIG group, 91.30%, 91.30%, 69.56% and 73.91% of patients developed anti-HBs titer ≥10 IU/L after the 1st, 2nd, 3rd and 4th doses of vaccine, respectively. Those in the vaccine-HBIG group maintained their anti-HBs titer ≥10 IU/L from the 1st to the 4th doses. In the vaccine-only group, 34.29% of patients gained protective antibody titer after receiving the 4th dose of vaccine. Subgroup analysis of age (pediatric vs adult and disease (acute lymphoblastic leukemia vs acute myeloid leukemia groups showed no effect of either on the development of protective antibody titer. The incidence of HBsAg positivity one month after the 4th dose of vaccine was 8.62%. No patient became positive for anti-HCV or HIV antibody before or after chemo therapy.Conclusion: Combined HBIG and vaccine may protect acute leukemia patients during the intensive chemotherapy period.

  1. Are heat stroke and physical exhaustion underestimated causes of acute hepatic failure?

    Institute of Scientific and Technical Information of China (English)

    Kilian Weigand; Carina Riediger; Wolfgang Stremmel; Christa Flechtenmacher; Jens Encke

    2007-01-01

    While cardiopulmonary symptoms are common in patients undergoing classical or, due to physical exercise,exertional heat stroke, the failure of other organs is a rarely described phenomenon. Here we present two cases of acute hepatic failure, one due to classic heat shock, while the other occurred while the patient was doing a marathon-type running. Both cases presented with very high transaminases and significantly elevated international normalized ratio (INR). No other causes for liver failure could be identified but physical exhaustion and hyperthermia.

  2. Acute Viral Hepatitis E Is Associated with the Development of Myocarditis

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    M. Premkumar

    2015-01-01

    Full Text Available Myocarditis, an inflammatory disease of heart muscle, is an important cause of dilated cardiomyopathy worldwide. Viral infection is an important cause of myocarditis. This condition presents with various symptoms, ranging from minimally symptomatic cases to fatal arrhythmia and cardiogenic shock, and may develop chronic myocarditis and dilated cardiomyopathy in some patients. We report the case of a 26-year-old patient with acute viral hepatitis E who developed symptomatic myocarditis. As far as we could search, this is probably the 3rd case report of this rare association.

  3. Acute tryptophan depletion attenuates brain-heart coupling following external feedback

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    Erik M Mueller

    2012-04-01

    Full Text Available External and internal performance feedback triggers neural and visceral modulations such as reactions in the medial prefrontal cortex and insulae or changes of heart period (HP. The functional coupling of neural and cardiac responses following feedback (cortico-cardiac connectivity is not well understood. While linear time-lagged within-subjects correlations of single-trial EEG and HP (cardio-electroencephalographic covariance-tracing, CECT indicate a robust negative coupling of EEG magnitude 300 ms after presentation of an external feedback stimulus with subsequent alterations of heart period (the so-called N300H phenomenon, the neurotransmitter systems underlying feedback-evoked cortico-cardiac connectivity are largely unknown. Because it has been shown that acute tryptophan depletion (ATD, attenuating brain serotonin (5-HT, decreases cardiac but not neural correlates of feedback processing, we hypothesized that 5-HT may be involved in feedback-evoked cortico-cardiac connectivity. In a placebo-controlled double-blind crossover design, twelve healthy participants received a tryptophan-free amino-acid drink at one session and a balanced amino-acid control-drink on another and twice performed a time-estimation task with feedback presented after each trial. N300H magnitude and plasma tryptophan levels were assessed. Results indicated a robust N300H after the control drink, which was significantly attenuated following ATD. Moreover, plasma tryptophan levels during the control session were correlated with N300H amplitude such that individuals with lower tryptophan levels showed reduced N300H. Together, these findings indicate that 5-HT is important for feedback-induced covariation of cortical and cardiac activity. Because individual differences in anxiety have previously been linked to 5-HT, cortico-cardiac coupling and feedback processing, the present findings may be particularly relevant for futures studies linking 5-HT to anxiety.

  4. Inhibition of extracellular HMGB1 attenuates hyperoxia-induced inflammatory acute lung injury

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    Maria Entezari

    2014-01-01

    Full Text Available Prolonged exposure to hyperoxia results in acute lung injury (ALI, accompanied by a significant elevation in the levels of proinflammatory cytokines and leukocyte infiltration in the lungs. However, the mechanisms underlying hyperoxia-induced proinflammatory ALI remain to be elucidated. In this study, we investigated the role of the proinflammatory cytokine high mobility group box protein 1 (HMGB1 in hyperoxic inflammatory lung injury, using an adult mouse model. The exposure of C57BL/6 mice to ≥99% O2 (hyperoxia significantly increased the accumulation of HMGB1 in the bronchoalveolar lavage fluids (BALF prior to the onset of severe inflammatory lung injury. In the airways of hyperoxic mice, HMGB1 was hyperacetylated and existed in various redox forms. Intratracheal administration of recombinant HMGB1 (rHMGB1 caused a significant increase in leukocyte infiltration into the lungs compared to animal treated with a non-specific peptide. Neutralizing anti-HMGB1 antibodies, administrated before hyperoxia significantly attenuated pulmonary edema and inflammatory responses, as indicated by decreased total protein content, wet/dry weight ratio, and numbers of leukocytes in the airways. This protection was also observed when HMGB1 inhibitors were administered after the onset of the hyperoxic exposure. The aliphatic antioxidant, ethyl pyruvate (EP, inhibited HMGB1 secretion from hyperoxic macrophages and attenuated hyperoxic lung injury. Overall, our data suggest that HMGB1 plays a critical role in mediating hyperoxic ALI through the recruitment of leukocytes into the lungs. If these results can be translated to humans, they suggest that HMGB1 inhibitors provide treatment regimens for oxidative inflammatory lung injury in patients receiving hyperoxia through mechanical ventilation.

  5. Nebulization of the acidified sodium nitrite formulation attenuates acute hypoxic pulmonary vasoconstriction

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    Surber Mark W

    2010-06-01

    Full Text Available Abstract Background Generalized hypoxic pulmonary vasoconstriction (HPV occurring during exposure to hypoxia is a detrimental process resulting in an increase in lung vascular resistance. Nebulization of sodium nitrite has been shown to inhibit HPV. The aim of this project was to investigate and compare the effects of nebulization of nitrite and different formulations of acidified sodium nitrite on acute HPV. Methods Ex vivo isolated rabbit lungs perfused with erythrocytes in Krebs-Henseleit buffer (adjusted to 10% hematocrit and in vivo anesthetized catheterized rabbits were challenged with periods of hypoxic ventilation alternating with periods of normoxic ventilation. After baseline hypoxic challenges, vehicle, sodium nitrite or acidified sodium nitrite was delivered via nebulization. In the ex vivo model, pulmonary arterial pressure and nitric oxide concentrations in exhaled gas were monitored. Nitrite and nitrite/nitrate were measured in samples of perfusion buffer. Pulmonary arterial pressure, systemic arterial pressure, cardiac output and blood gases were monitored in the in vivo model. Results In the ex vivo model, nitrite nebulization attenuated HPV and increased nitric oxide concentrations in exhaled gas and nitrite concentrations in the perfusate. The acidified forms of sodium nitrite induced higher levels of nitric oxide in exhaled gas and had longer vasodilating effects compared to nitrite alone. All nitrite formulations increased concentrations of circulating nitrite to the same degree. In the in vivo model, inhaled nitrite inhibited HPV, while pulmonary arterial pressure, cardiac output and blood gases were not affected. All nitrite formulations had similar potency to inhibit HPV. The tested concentration of appeared tolerable. Conclusion Nitrite alone and in acidified forms effectively and similarly attenuates HPV. However, acidified nitrite formulations induce a more pronounced increase in nitric oxide exhalation.

  6. Methylene blue attenuates acute liver injury induced by paraquat in rats.

    Science.gov (United States)

    Chen, Jun-Liang; Dai, Li; Zhang, Peng; Chen, Wei; Cai, Gao-Shan; Qi, Xiao-Wei; Hu, Ming-Zhu; Du, Bin; Pang, Qing-Feng

    2015-09-01

    Paraquat (PQ) poisoning often leads to severe oxidative liver injury. Recent studies have reported that methylene blue (MB) can prevent oxidative stress-induced diseases. This study tested the hypothesis that MB treatment reduced acute liver injury induced by PQ in rats. Adult male Sprague-Dawley (SD) rats were randomly divided into four groups: (1) normal group, (2) MB group (2mg/kg i.p.), (3) PQ group (35 mg/kg i.p.) and (4) PQ+MB group (MB 2mg/kg i.p. administrated 2h after PQ). We evaluated the changes of liver histopathology, serum liver enzymatic activities, oxidative stress, heme oxygenase-1 expression, and mitochondrial permeability transition. The rats were injected with PQ produced liver injury, evidenced by histological changes and elevated serum alkaline phosphatase and alanine transaminase levels; PQ also led to oxidative stress, an increase of malondialdehyde content and mitochondrial permeability transition pore opening. Pathological damage and all of the above mentioned markers were reversed in the animals treated with MB than in those who received PQ alone. Meanwhile, MB significantly increased the contents of superoxide dismutase, adenosine triphosphate and the expression of heme oxygenase-1. In conclusion, MB had a protective effect against PQ-induced hepatic damage in rats. The mechanisms of the protection seem to be the inhibition of mitochondrial permeability transition opening and the increase of heme oxygenase-1 expression.

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

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    Ye Han

    2015-01-01

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

  8. Acute onset anarthria without hepatic manifestation: a rare presentation of Wilson disease.

    Science.gov (United States)

    Verma, Rajesh; Bhandari, Aveg; Tiwari, Navin; Chaudhari, Tejendra S

    2013-08-20

    Wilson disease (WD) is one of the few inherited but treatable disorder mainly affecting the liver and brain resulting in severe disability or death if left untreated. Hence, it is important to keep a high index of suspicion for diagnosing this clinical entity in appropriate clinical settings. The clinical presentation can be quite variable and they may present solely with neurological features sans hepatic symptoms. Such neurological manifestations usually follow subacute to chronic course. Acute onset anarthria as the heralding and predominant presenting feature has been rarely reported in the literature. We reported a case of a 12-year-old girl who presented with acute onset anarthria and dystonia of 1-month duration. On further evaluation, a diagnosis of WD was made. The patient showed partial improvement after she was started on copper chelating agents and anticholinergics.

  9. α1-ANTITRYPSIN ATTENUATES ENDOTOXIN-INDUCED ACUTE LUNG INJURY IN RABBITS

    Institute of Scientific and Technical Information of China (English)

    揭志军; 蔡映云; 杨文兰; 金美玲; 朱威; 祝慈芳

    2003-01-01

    Objective To investigate whether pretreatment with α1-AT can attenuate acute lung injury (ALI) in rabbits induced with endotoxin. Methods Thirty-two New Zealand rabbits were randomly assigned to four groups(n=8):1.Infusion of endotoxin(Lipopolysaccharide,LPS 500μg/kg)without α1-AT (group LPS).2.Infusion α1-AT 120mg/kg at 15min before challenge with LPS(group LAV).3.Infusion of α1-AT 120mg/kg(group AAT).4 Infusion of saline 4ml/kg as control (group NS).Arterial blood gases,peripheral leukocyte counts and airway pressure were recorded every 1h.Physiologic intrapulmonary shunting (Qs/Qt) was measured every 4h.After 8h the bloods were collected for measurement of plasma concentration and activity of α1-AT.Then bronchoalveolar lavage fluid (BALF)was collected for measurement of concentrations of total protein (TP),interleukin-8(IL-8),tumor necrosis factor(TNF-α),the activities of elastase-like and α1-AT,total phospholipids(TPL) and disaturated phosphatidylcholine (DSPC).In addition,the wet-to-dry lung weight ratio(W/D) was measured. Results After infusion of endotoxin,it was observed that PaO2,peripheral luekocyte counts,total respiratory compliance progressively decreased and Ppeak and Qs/Qt increased comparing with the baseline values.In contrast to group NS,the increased plasma concentration but reduced activity of α1-AT was found in group LPS.In the BALF,the activity of α1-AT,TPL,DSPC/TPL were lower,but the concentrations of albumin,IL-8,TNF-α,and the activity of NE were higher.The ratio of W/D also increased.The pretreatment of α1-AT attenuated the deterioration of oxygenation,the reduction of compliance and the deterioration of other physiological,biochemical parameters mentioned above. Conclusion Pretreatment with α1-AT could attenuate endotoxin-induced lung injury in rabbits.Those beneficial effects of α1-AT might be due in part to the inhibitory effect on neutrophil elastase.

  10. Changes of High Mobility Group box 1 in Serum of Pig Acute Hepatic Failure Model and Significance

    Institute of Scientific and Technical Information of China (English)

    Fan ZHANG; Yongwen HE; Zhongping DUAN

    2008-01-01

    The role of the high mobility group box 1 (HMGB-1) in acute hepatic failure and the ef- fect of artificial liver support system treatment on HMGB-1 level were investigated. Pig models of acute hepatic failure were induced by D-galactosamine and randomly divided into two groups with or without artificial liver support system treatment. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels were detected by the enzyme linked immunosorbent assay (ELISA), the expression of HMGB-1 by Western blot, and serum levels of HMGB-1, liver function and hepatic pathology were observed after artificial liver support system treatment. The levels of TNF-α and IL-1β were increased and reached the peak at 24th h in the acute hepatic failure group, then quickly decreased. The serum level of HMGB-1 was increased at 24th h in the acute hepatic failure group and reached the peak at 48th h, then kept a stable high level. Significant liver injury appeared at 24th h and was continuously getting worse in the pig models of acute hepatic failure. In contrast, the liver injury was significantly alleviated and serum level of HMGB-1 was significantly decreased in the group treated with artificial liver support system (P<0.05). It was suggested that HMGB-1 may participate in the inflammatory response and liver injury in the late stage of the acute liver failure. Artificial liver support system treatment can reduce serum HMGB-1 level and relieve liver pathological damage.

  11. Inhibition of soluble epoxide hydrolase attenuates hepatic fibrosis and endoplasmic reticulum stress induced by carbon tetrachloride in mice

    Energy Technology Data Exchange (ETDEWEB)

    Harris, Todd R. [Department of Entomology and Comprehensive Cancer Center, University of California, Davis, CA 95616 (United States); Bettaieb, Ahmed [Department of Nutrition, University of California, Davis, CA 95616 (United States); Kodani, Sean; Dong, Hua [Department of Entomology and Comprehensive Cancer Center, University of California, Davis, CA 95616 (United States); Myers, Richard; Chiamvimonvat, Nipavan [Department of Internal Medicine: Cardiovascular, University of California, Davis, CA 95616 (United States); Haj, Fawaz G. [Department of Nutrition, University of California, Davis, CA 95616 (United States); Department of Internal Medicine: Endocrinology, Diabetes and Metabolism, University of California, Davis, CA 95616 (United States); Hammock, Bruce D., E-mail: bdhammock@ucdavis.edu [Department of Entomology and Comprehensive Cancer Center, University of California, Davis, CA 95616 (United States)

    2015-07-15

    Liver fibrosis is a pathological condition in which chronic inflammation and changes to the extracellular matrix lead to alterations in hepatic tissue architecture and functional degradation of the liver. Inhibitors of the enzyme soluble epoxide hydrolase (sEH) reduce fibrosis in the heart, pancreas and kidney in several disease models. In this study, we assess the effect of sEH inhibition on the development of fibrosis in a carbon tetrachloride (CCl{sub 4})-induced mouse model by monitoring changes in the inflammatory response, matrix remolding and endoplasmic reticulum stress. The sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) was administered in drinking water. Collagen deposition in the liver was increased five-fold in the CCl{sub 4}-treated group, and this was returned to control levels by TPPU treatment. Hepatic expression of Col1a2 and 3a1 mRNA was increased over fifteen-fold in the CCl{sub 4}-treated group relative to the Control group, and this increase was reduced by 50% by TPPU treatment. Endoplasmic reticulum (ER) stress observed in the livers of CCl{sub 4}-treated animals was attenuated by TPPU treatment. In order to support the hypothesis that TPPU is acting to reduce the hepatic fibrosis and ER stress through its action as a sEH inhibitor we used a second sEH inhibitor, trans-4-(4-[3-(4-trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy)-benzoic acid (t-TUCB), and sEH null mice. Taken together, these data indicate that the sEH may play an important role in the development of hepatic fibrosis induced by CCl{sub 4}, presumably by reducing endogenous fatty acid epoxide chemical mediators acting to reduce ER stress. - Highlights: • We administer an inhibitor of sEH in a CCl4 murine model. • sEH inhibition reduces liver collagen deposition and pro-fibrotic gene expression. • sEH inhibition induces MMP-1a activity.

  12. Alterations in bronchoalveolar lavage fluid during ischemia-induced acute hepatic failure in the pig.

    Science.gov (United States)

    Kostopanagiotou, Georgia; Routsi, Christina; Smyrniotis, Vassilios; Lekka, Marilena E; Kitsiouli, Eirini; Arkadopoulos, Nikolaos; Nakos, George

    2003-05-01

    The objective of this controlled experimental animal study was to evaluate whether acute hepatic failure (AHF) can cause acute lung injury (ALI) and to investigate possible pathophysiologic mechanisms. Seventeen domestic pigs were randomly assigned to AHF and sham groups. AHF was induced by surgical devascularization of liver in 10 animals. Seven animals were sham operated. Hemodynamics, lung mechanics, extravascular lung water (EVLW), and intracranial pressure, blood gas, liver function tests, and serum endotoxin levels were measured. Cells count, total protein, and phospholipids and phospholipases A(2) were determined in the bronchoalveolar lavage (BAL) fluid. Measurements were obtained after the insertion of central lines and 4 hours and 7 hours after the completion of the surgical procedure. Hemodynamic, biochemical, neuromonitoring, and histologic data confirmed the development of liver failure. Seven hours after devascularization, EVLW was higher in AHF (13.7 +/- 1.8 mL/kg) compared with the sham group (5.9 +/- 0.7 mL/kg) (P <.05); in AHF, increase of neutrophils (5% +/- 8% to 25% +/- 8%, P <.001), total protein (6.2 +/- 3.7 to 11.2 +/- 6.5 microg/mL, P <.048), and phospholipase A(2) (1.43 +/- 0.56 to 2.38 +/- 1.38 nmoL/mL/h, P <.03) and decrease in PAF-acetylhydrolase (0.114 +/- 0.128 to 0.039 +/- 0.038 nmol/mL/h, P <.01) compared with baseline were observed; total phospholipids decreased in AHF and increased in the sham model. Histologic examination confirmed lesions compatible with acute lung injury. In conclusion, AHF due to hepatic devascularization induced acute lung injury, confirmed by the increase of inflammatory cells in the alveoli as well as by histologic findings. The decreased PAF-AcH and the increased phospholipase A(2) may play a significant role in the perpetuation of inflammation accompanied by surfactant disorders.

  13. Ceftriaxone attenuates acute cocaine‐evoked dopaminergic neurotransmission in the nucleus accumbens of the rat

    Science.gov (United States)

    Rasmussen, B A; Tallarida, C S; Scholl, J L; Forster, G L; Unterwald, E M; Rawls, S M

    2015-01-01

    Background and Purpose Ceftriaxone is a β‐lactam antibiotic and glutamate transporter activator that reduces the reinforcing effects of psychostimulants. Ceftriaxone also reduces locomotor activation following acute psychostimulant exposure, suggesting that alterations in dopamine transmission in the nucleus accumbens contribute to its mechanism of action. In the present studies we tested the hypothesis that pretreatment with ceftriaxone disrupts acute cocaine‐evoked dopaminergic neurotransmission in the nucleus accumbens. Experimental Approach Adult male Sprague–Dawley rats were pretreated with saline or ceftriaxone (200 mg kg−1, i.p. × 10 days) and then challenged with cocaine (15 mg kg−1, i.p.). Motor activity, dopamine efflux (via in vivo microdialysis) and protein levels of tyrosine hydroxylase (TH), the dopamine transporter and organic cation transporter as well as α‐synuclein, Akt and GSK3β were analysed in the nucleus accumbens. Key Results Ceftriaxone‐pretreated rats challenged with cocaine displayed reduced locomotor activity and accumbal dopamine efflux compared with saline‐pretreated controls challenged with cocaine. The reduction in cocaine‐evoked dopamine levels was not counteracted by excitatory amino acid transporter 2 blockade in the nucleus accumbens. Pretreatment with ceftriaxone increased Akt/GSK3β signalling in the nucleus accumbens and reduced levels of dopamine transporter, TH and phosphorylated α‐synuclein, indicating that ceftriaxone affects numerous proteins involved in dopaminergic transmission. Conclusions and Implications These results are the first evidence that ceftriaxone affects cocaine‐evoked dopaminergic transmission, in addition to its well‐described effects on glutamate, and suggest that its ability to attenuate cocaine‐induced behaviours, such as psychomotor activity, is due in part to reduced dopaminergic neurotransmission in the nucleus accumbens. PMID:26375494

  14. Intravenous transplantation of mesenchymal stem cells attenuates oleic acid induced acute lung injury in rats

    Institute of Scientific and Technical Information of China (English)

    XU Yu-lin; LIU Ying-long; WANG Qiang; LI Gang; L(U) Xiao-dong; KONG Bo

    2012-01-01

    Background Acute lung injury (ALI) and end-stage acute respiratory distress syndrome (ARDS) were among the most common causes of death in intensive care units.The activation of an inflammatory response and the damage of pulmonary epithelium and endotheliumwerethe hallmark of ALI/ARDS.Recent studies had demonstrated the importance of mesenchymal stem cells (MSCs) in maintaining the normal pulmonary endothelial and epithelial function as well as participating in modulating the inflammatory response and they are involved in epithelial and endothelial repair after injury.Here,our study demonstrates MSCs therapeutic potential in a rat model of ALI/ARDS.Methods Bone marrow derived MSCs were obtained from Sprague-Dawley (SD) rats and their differential potential was verified.ALl was induced in rats byoleic acid (OA),and MSCs were transplanted intravenously.The lung injury and the concentration of cytokines in plasma and lung tissue extracts were assessed at 8 hours,24 hours and 48 hours after OA-injection.Results The histological appearance and water content in rat lung tissue were significantly improved at different time points in rats treated with MSCs.The concentration of tumor necrosis factor-α and intercellular adhesion molecular-1 in rats plasma and lung tissue extracts were significantly inhibited after intravenous transplantation of MSCs,whereas interleukin-10 was significantly higher after MSCs transplantation at 8 hours,24 hours and 48 hours after OA-challenge.Conclusions Intravenous transplantation of MSCs could maintain the integrity of the pulmonary alveolar-capillary barrier and modulate the inflammatory response to attenuate the experimental ALI/ARDS.Transplantation of MSCs could be a novel cell-based therapeutic strategy for prevention and treatment of ALI/ARDS.

  15. Does Fasciola hepatica infection modify the response of acute hepatitis C virus infection to IFN-α treatment?

    Institute of Scientific and Technical Information of China (English)

    Mehmet Sahin; Mehmet Isler; Altug Senol; Mustafa Demirci; Zeynep Dilek Aydin

    2005-01-01

    Immunologic response to acute hepatitis C is mainly a Th1 response, whereas fasciolopsiasis is associated with a diverse T-cell response. Interferon-alpha has immunomodulatory effects and enhances Th1 immune response. Fasciola infection could theoretically interfere with the Th1 immune response, even when acquired after an initial response to interferon-alpha treatment for acute hepatitis C virus (HCV) infection. We report here the case of a male patient who acquired Fasciola hepatica infection after an initial response to IFN-alpha therapy with a favorable outcome

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

    OpenAIRE

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

    2009-01-01

    Acute pancreatitis, an uncommon side effect of pegylated interferon α (PEG-IFN α) and ribavirin (RBV) combination therapy, has rarely been reported in the English language literature. Here, acute pancreatitis associated with PEG-IFN plus RBV treatment is described in three patients with chronic hepatitis C, genotype 1b with high serum hepatitis C virus RNA levels. The patients had been started on weekly subcutaneous injections of PEG-IFN α (60, 80, and 90 μg) plus a daily oral dose of RBV (60...

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

    Directory of Open Access Journals (Sweden)

    Yingqun Zhou

    2015-01-01

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

  18. Opuntia ficus-indica seed attenuates hepatic steatosis and promotes M2 macrophage polarization in high-fat diet-fed mice.

    Science.gov (United States)

    Kang, Jung-Woo; Shin, Jun-Kyu; Koh, Eun-Ji; Ryu, Hyojeong; Kim, Hyoung Ja; Lee, Sun-Mee

    2016-04-01

    Opuntia ficus-indica (L.) is a popular edible plant that possesses considerable nutritional value and exhibits diverse biological actions including anti-inflammatory and antidiabetic activities. In this study, we hypothesized that DWJ504, an extract of O ficus-indica seed, would ameliorate hepatic steatosis and inflammation by regulating hepatic de novo lipogenesis and macrophage polarization against experimental nonalcoholic steatohepatitis. Mice were fed a normal diet or a high-fat diet (HFD) for 10 weeks. DWJ504 (250, 500, and 1000 mg/kg) or vehicle (0.5% carboxymethyl cellulose) were orally administered for the last 4 weeks of the 10-week HFD feeding period. DWJ504 treatment remarkably attenuated HFD-induced increases in hepatic lipid content and hepatocellular damage. DWJ504 attenuated increases in sterol regulatory element-binding protein 1 and carbohydrate-responsive element-binding protein expression and a decrease in carnitine palmitoyltransferase 1A. Although DWJ504 augmented peroxisome proliferator-activated receptor α protein expression, it attenuated peroxisome proliferator-activated receptor γ expression. Moreover, DWJ504 promoted hepatic M2 macrophage polarization as indicated by attenuation of the M1 marker genes and enhancement of M2 marker genes. Finally, DWJ504 attenuated expression of toll-like receptor 4, nuclear factor κB, tumor necrosis factor α, interleukin 6, TIR-domain-containing adapter-inducing interferon β, and interferon β levels. Our results demonstrate that DWJ504 prevented intrahepatic lipid accumulation, induced M2 macrophage polarization, and suppressed the toll-like receptor 4-mediated inflammatory signaling pathway. Thus, DWJ504 has therapeutic potential in the prevention of nonalcoholic fatty liver disease.

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

    Science.gov (United States)

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

    2014-01-01

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

  20. Oral exposure to Phytomonas serpens attenuates thrombocytopenia and leukopenia during acute infection with Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Rosiane V da Silva

    Full Text Available Mice infected with Trypanosoma cruzi, the agent of Chagas disease, rapidly develop anemia and thrombocytopenia. These effects are partially promoted by the parasite trans-sialidase (TS, which is shed in the blood and depletes sialic acid from the platelets, inducing accelerated platelet clearance and causing thrombocytopenia during the acute phase of disease. Here, we demonstrate that oral immunization of C57BL/6 mice with Phytomonas serpens, a phytoflagellate parasite that shares common antigens with T. cruzi but has no TS activity, reduces parasite burden and prevents thrombocytopenia and leukopenia. Immunization also reduces platelet loss after intraperitoneal injection of TS. In addition, passive transfer of immune sera raised in mice against P. serpens prevented platelet clearance. Thus, oral exposure to P. serpens attenuates the progression of thrombocytopenia induced by TS from T. cruzi. These findings are not only important for the understanding of the pathogenesis of T. cruzi infection but also for developing novel approaches of intervention in Chagas disease.

  1. Blockade of high mobility group box-1 protein attenuates experimental severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Hidehiro Sawa; Takashi Ueda; Yoshifumi Takeyama; Takeo Yasuda; Makoto Shinzeki; Takahiro Nakajima; Yoshikazu Kuroda

    2006-01-01

    AIM: To examine the effects of anti-high mobility group box 1 (HMGB1) neutralizing antibody in experimental severe acute pancreatitis (SAP).METHODS: SAP was induced by creating closed duodenal loop in C3H/HeN mice. SAP was induced immediately after intraperitoneal injection of anti-HMGB1 neutralizing antibody (200 μg). Severity of pancreatitis, organ injury (liver, kidney and lung), and bacterial translocation to pancreas was examined 12 h after induction of SAP.RESULTS: Anti-HMGB1 neutralizing antibody significantly improved the elevation of the serum amylase level and the histological alterations of pancreas and lung in SAP.Anti-HMGB1 antibody also significantly ameliorated the elevations of serum alanine aminotransferase and creatinine in SAP. However, anti-HMGB1 antibody worsened the bacterial translocation to pancreas.CONCLUSION: Blockade of HMGB1 attenuated the development of SAP and associated organ dysfunction,suggesting that HMGB1 may act as a key mediator for inflammatory response and organ injury in SAP.

  2. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930140 Hepatocyte stimulator peptide and itsclinical significance in viral hepatitis.ZHOUWeiping(周卫平),et al.Instit Viral Hepatitis,Chongqing Med Univ,630010.Chin J InternMed 1992;31(10):626-628.Hepatocyte stimulator peptide(HSP)is anewly developed hepatic stimulator substance.Its monoclonal antibodies have been obtained inour laboratory.In this study,HSP was deter-mined in the sera of 315 subjects including pa-

  3. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    2010349 Relationships between serum hepatitis B virus load in mothers,free maternal DNA in peripheral blood of newborns and hepatitis B virus infection of newborns. WEI Junni(魏俊妮),et al. Dept Epidemiol,Shanxi Med Univ,Taiyuan 030001. Chin J Infect Dis 2010;28(5):297-300. Objective To study the relationships between serum hepatitis B virus (HBV) DNA level

  4. Mechanism research on the effects of fasudil to postoperative acute hepatic failure induced by hepatic ischemia & hepatectomy on rats with obstructive jaundice

    Institute of Scientific and Technical Information of China (English)

    Shao-Hua Chen; Li Cheng

    2015-01-01

    Objective:To establish a kind of animal model of postoperative acute hepatic failure induced by hepatic ischemia & hepatectomy on rats with obstructive jaundice, which could show similar clinical pathophysiological changes in hunman beings. To investigate the influence of fasudil to this model.Method:Selected 96 Wistar big rats as animal model of obstructive jaundice, which were treated with ligation and cuting off common bile duct. Rats in low-dose group were immediately injected fasudil of 10 mg/kg through portal vein after hepatectomy, while rats in high-dose group were immediately injected fasudil of 30 mg/kg through portal vein after hepatectomy, rats in control group were immediately injected equivalent normal saline through portal vein after hepatectomy. To determine the serum ALT, AST, TBIL (tumor necrosis factor-α, TNF-α)and (interferon-γ, INF-γ) levels in postoperative rats with hepatic failure within 6 h; to determine the (superoxide dismutase, SOD) activity and (malondialdehyde, MDA) content in hepatic tissue; hepatic tissue HE staining to observe the pathological injury; to observe animal model 96 h of survival rate.Results:That Proceeding internal biliary drainage operation to rats after obstruction for 14 h, and blocking 70% of hepatic blood supply, excising remnant liver after 30 min was in accordance with criteria of hepatic failure animal, and was deserved to further research. Compared with control group, serum AST, ALT, TBIL, TNF-α, INF-γ levels decreased in fasudil treatment group, SOD activity increased in hepatic tissue, MDA content decreased, pathological injury in hepatic tissue reduced, rats 96 h of survival rate increased, and the effects of high-dose group were more obvious than that in low-dose group.Conclusion:A surgical hepatic failure model in rat was established, which showed similar clinical pathophysiological changes in hunman beings. In addition, we have found that fasudil possibly played a role of protection to hepatic

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

    Science.gov (United States)

    ... 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 ...

  6. Vascular endothelial growth factor attenuates hepatic sinusoidal capillarization in thioacetamide-induced cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Hao Xu; Bao-Min Shi; Xiao-Fei Lu; Feng Liang; Xing Jin; Tai-Huang Wu; Jian Xu

    2008-01-01

    AIM: To investigate the effect of vascular endothelial growth factor (VEGF) transfection on hepatic sinusoidal capillarization.MEthODS: Enhanced green fluorescent protein (EGFP)/VEGF transfection was confirmed by immunofluorescencemicroscopy and immunohistoche-mistry both in primaryhepatocytes and in normal liven Cirrhotic rats weregenerated by thioacetamide (TAA) administration andthen divided into a treatment group, which receivedinjections of 400 μg of plasmid DNA encoding an EGFP-VEGF fusion protein, and a blank group, which receivedan equal amount of normal saline through the portalvein. The portal vein pressure was measured in the normal and cirrhotic state, in treated and blank groups.The average number of fenestrae per hepatic sinusoidwas determined using transmission electron microscopy(TEM), while the relative abundance of VEGF transcriptswas examined by Gene array.RESULTS: Green fluorescent protein was observed in the cytoplasms of liver cells under immunofluorescence microscopy 24 h after transfection with EGFP/VEGFplasmid in vitro. Staining with polyclonal antibodies against VEGF illustrated that hepatocytes expressed immunodetectable VEGF both in vitro and in vitro. There were significant differences in the number of fenestrae and portal vein pressures between normal and cirrhotic rats (7.40±1.71 vs 2.30± 2.26 and 9.32± 0.85 cmH2Ovs 27.92± 0.90 cmH2O1, P < 0.02), between cirrhotic and treated rats (2.30 + 1.16 cmH2O vs 4.60± 1.65 and 17.92± 0.90 cmH2O vs 15.52±0.93 cmH20, P < 0.05)and between the treatment group and the blank group (4.60±1.65 cmH20 vs 2.10 ± 1.10 cmH20 and 25.52 +0.93 cmH20 vs 17.26 ± 1.80 cmH20, P < 0.05). Gene-array analysis revealed that the relative abundance oftranscripts of VEGF family members decreased in the cirrhotic state and increased after transfection. CONCLUSION: Injection of a plasmid encoding VEGFthrough the portal vein is an effective method toinduce the formation of fenestrae and decrease portalvein

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

    Science.gov (United States)

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

    2014-01-01

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

  8. Salmon Thrombin as a Treatment to Attenuate Acute Pain and Promote Tissue Healing by Modulating Local Inflammation

    Science.gov (United States)

    2012-12-01

    trauma and in association with the absence of pain . Early cleavage of PAR1 by thrombin may provide its anti- nociceptive properties. We were very...1-1002 TITLE: Salmon Thrombin as a Treatment to Attenuate Acute Pain and Promote Tissue Healing by Modulating Local Inflammation... Pain and 5a. CONTRACT NUMBER Promote Tissue Healing by Modulating Local Inflammation 5b. GRANT NUMBER W81XWH-10-1-1002 5c. PROGRAM ELEMENT

  9. Cerebrolysin attenuates cerebral and hepatic injury due to lipopolysaccharide in rats.

    Science.gov (United States)

    Abdel-Salam, O M E; Omara, E A; Mohammed, N A; Youness, E R; Khadrawy, Y A; Sleem, A A

    2013-12-01

    This study aimed to investigate the effect of cerebrolysin on oxidative stress in the brain and liver during systemic inflammation. Rats were intraperitoneally challenged with a single subseptic dose of lipopolysaccharide (LPS; 300 μg/kg) without or with cerebrolysin at doses of 21.5, 43 or 86 mg/kg. After 4 h, rats were euthanized and the brain and liver tissues were subjected to biochemical and histopathological analyses. Cerebrolysin revealed inhibitory effects on the elevation of lipid peroxidation and nitric oxide induced by LPS. In contrast, the decrease in reduced glutathione level and paraoxonase activity induced by LPS was attenuated by an injection of cerebrolysin in a dose-dependent manner. Moreover, cerebrolysin reduced LPS-induced activation of brain NF-κB and reversed LPS-induced decline of brain butyrylcholinesterase and acetylcholinesterase activities in a dose-dependent manner. Histopathological analyses revealed that neuronal damage and liver necrosis induced by LPS were ameliorated by cerebrolysin dose-dependently. Cerebrolysin treatment dose-dependently attenuated LPS-induced expressions in cyclooxygenase 2, inducible nitric oxide synthase, and caspase-3 in the cortex or striatum as well as the liver. These results suggest that cerebrolysin treatment might have beneficial therapeutic effects in cerebral inflammation. Cerebrolysin might also prove of value in liver disease and this possibility requires further exploration.

  10. Periostin down-regulation attenuates the pro-fibrogenic response of hepatic stellate cells induced by TGF-β1.

    Science.gov (United States)

    Hong, Li; Shejiao, Dai; Fenrong, Chen; Gang, Zhao; Lei, Dong

    2015-10-01

    Liver fibrosis is characterized by an exacerbated accumulation of deposition of the extracellular matrix (ECM), and the activation of hepatic stellate cells (HSC) plays a pivotal role in the development of liver fibrosis. Periostin has been shown to regulate cell adhesion, proliferation, migration and apoptosis; however, the involvement of periostin and its role in transforming growth factor (TGF)-β1-induced HSC activation remains unclear. We used RT-PCR and Western blot to evaluate the expression level of periostin in hepatic fibrosis tissues and HSCs, respectively. Cell proliferation was determined using the Cell Proliferation ELISA BrdU kit, cell cycle was analysed by flow cytometry. The expression of α-smooth muscle actin (α-SMA), collagen I, TGF-β1, p-Smad2 and p-Smad3 were determined by western blot. Our study found that periostin was up-regulated in liver fibrotic tissues and activated HSCs. In addition, siRNA-periostin suppressed TGF-β1-induced HSC proliferation. The HSC transfected with siRNA-periostin significantly inhibited TGF-β1-induced expression levels of α-SMA and collagen I. Furthermore, TGF-β1 stimulated the expression of periostin, and siRNA-periostin attenuated TGF-β1-induced Smad2/3 activation in HSCs. These results suggest that periostin may function as a novel regulator to modulate HSC activation, potentially by promoting the TGF-β1/Smad signalling pathway, and propose a strategy to target periostin for the treatment of liver fibrosis.

  11. Intensive insulin treatment attenuates burn-initiated acute lung injury in rats: role of the protective endothelium.

    Science.gov (United States)

    Zhang, Wan-Fu; Zhu, Xiong-Xiang; Hu, Da-Hai; Xu, Cheng-Feng; Wang, Yun-Chuan; Lv, Gen-Fa

    2011-01-01

    Nonmetabolic effects of intensive insulin therapy in critically ill patients have been reported, but the underlying mechanisms are unclear. This study was designed to test the hypothesis that intensive insulin treatment would attenuate burn-induced acute lung injury by protecting the pulmonary microvascular endothelium. The rat model of burn injury was achieved by exposure to 92°C water for 18 seconds. The rats were randomly allocated into the sham, burn/normal saline (NS), and burn/intensive insulin treatment groups. Blood glucose level was maintained between 5 and 7 mmol/L in rats in the burn/intensive insulin treatment group. Pulmonary injury was assessed by hematoxylin and eosin staining, scanning electron microscopy, bronchoalveolar lavage fluid protein concentrations, the lung wet:dry weight ratio, and lung myeloperoxidase activity. Pulmonary microvascular endothelial cells were examined by transmission electron microscopy. Western blotting was used to determine the protein expression of caspase-3. Intensive insulin treatment markedly attenuated the acute lung injury, revealed by improvements in histological features and significant decreases in bronchoalveolar lavage fluid protein concentrations, pulmonary wet:dry weight ratio, and myeloperoxidase activity at 12 hours after injury (P insulin treatment group when compared with the burn/NS group. Overall, intensive insulin treatment efficiently attenuated pulmonary microvascular endothelial cell dysfunction, decreased cell apoptosis, and inhibited acute lung injury after a burn. These findings may be useful in preventing organ failure after burn injury.

  12. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970349 Primary structure and variability of partialsequences in nonstructural gene 5 region of hepatitis Gvirus, CHANG Jinhong(常锦红), et al. Hepatol Instis,People’s Hosp, Beijing Med Univ, Beijing, 100044. NatlMed J China 1997; 77(3): 178-182. Objective: To sequence partial genome of hepatitis G

  13. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    2009209 Effects of chronic hepatitis B virus infection on human hepatic cytochrome P450 2C9.ZHO Fuping(周福平),et al.Dept Infect Dis,Shanghai Changzheng Hosp,Shanghai 200003.Chin J Infect Dis,2009;27(2):94-98.

  14. Hepatitis

    Science.gov (United States)

    ... inflammation of the liver.” This inflammation can be caused by a wide variety of toxins, drugs, and metabolic diseases, as well as infection. There are at least 5 hepatitis viruses. Hepatitis A is contracted when a child eats food or drinks water that is contaminated with the virus or has ...

  15. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    920691 The determination of serum hepa-titis B virus DNA by polymerase chain rea-ction in hepatitis B patients treated withalpha-interferon. XU. Jianye(徐建业), et al.Centr Lab, Chongqing Cancer Instit, 630030.Chin J Intern Med, 1992; 31(5): 278-280. To clarify the status of HBV in serum of

  16. Arterial steroid injection therapy can inhibit the progression of severe acute hepatic failure toward fulminant liver failure

    Institute of Scientific and Technical Information of China (English)

    Kazuhiro Kotoh; Tsuyoshi Tajima; Yoshiki Asayama; Kousei Ishigami; Masakazu Hirakawa; Munechika Enjoji; Makoto Nakamuta; Tsuyoshi Yoshimoto; Motoyuki Kohjima; Shusuke Morizono; Shinsaku Yamashita; Yuki Horikawa; Kengo Yoshimitsu

    2006-01-01

    AIM: To utilize transcatheter arterial steroid injection therapy (TASIT) via the hepatic artery to reduce hepatic macrophage activity in patients with severe acute hepatic failure.METHODS: Thirty-four patients with severe acute hepatic failure were admitted to our hospital between June 2002 to June 2006 providing for the possibility of liver transplantation (LT). Seventeen patients were treated using traditional liver supportive procedures, and the other 17 patients additionally underwent TASIT with 1000 mg methylprednisolone per day for 3 continuous days.RESULTS: Of the 17 patients who received TASIT, 13 were cured without any complications, 2 died, and 2 underwent LT. Of the 17 patients who did not receive TASIT, 4 were self-limiting, 7 died, and 6 underwent LT.Univariate logistic analysis revealed that ascites, serum albumin, prothrombin time, platelet count, and TASIT were significant variables for predicating the prognosis.Multivariate logistic regression analysis using stepwise variable selection showed that prothrombin time, platelet count, and TASIT were independent predictive factors.CONCLUSION: TASIT might effectively prevent the progression of severe acute hepatic failure to a fatal stage of fulminant liver failure.

  17. Sustained viral response of a case of acute hepatitis C virus infection via needle-stick injury

    Institute of Scientific and Technical Information of China (English)

    Takayuki Kogure; Yu Nakagome; Masashi Ninomiya; Tooru Shimosegawa; Yoshiyuki Ueno; Noriatsu Kanno; Koji Fukushima; Yoko Yamagiwa; Futoshi Nagasaki; Eiji Kakazu; Yasunori Matsuda; Osamu Kido

    2006-01-01

    A 29-year-old nurse with a hepatitis C virus (HCV) infection caused by needle-stick injury was treated with interferon-beta starting about one year after the onset of acute hepatitis. The patient developed acute hepatitis C with symptoms of general fatigues, jaundice, and ascites 4 wk after the needle-stick injury. When these symptoms were presented, the patient was pregnant by artificial insemination. She hoped to continue her pregnancy.After delivery, biochemical liver enzyme returned to normal levels. Nevertheless, HCV RNA was positive and the pathological finding indicated a progression to chronicity. The genotype was 1b with low viral load.Daily intravenous injection of interferon-beta at the dosage of six million units was started and continued for eight weeks. HCV was eradicated without severe adverse effects. In acute hepatitis C, delaying therapy is considered to reduce the efficacy but interferon-beta therapy is one of the useful treatments for hepatitis C infection in chronic phase.

  18. Maternal resveratrol intake during lactation attenuates hepatic triglyceride and fatty acid synthesis in adult male rat offspring

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    Masato Tanaka

    2017-03-01

    regulates the lipogenic pathway by activating genes involved in triglyceride and fatty acid synthesis. The present study showed significant downregulation of hepatic fatty acid synthase (FAS and acetyl-CoA carboxylase (ACC levels in the CR group. These results indicated that maternal resveratrol intake during lactation suppressed SREBP-1c cleavage and nuclear translocation and repressed SREBP-1c target gene expression such as FAS and ACC in the livers of adult male offspring. These changes attenuate hepatic triacylglycerol and fatty acid synthesis in adult male offspring.

  19. Calpain inhibitor attenuated optic nerve damage in acute optic neuritis in rats

    Science.gov (United States)

    Das, Arabinda; Guyton, M. Kelly; Smith, Amena; Wallace, Gerald; McDowell, Misty L.; Matzelle, Denise D.; Ray, Swapan K.; Banik, Naren L.

    2012-01-01

    Optic neuritis (ON), which is an acute inflammatory autoimmune demyelinating disease of the central nervous system (CNS), often occurs in multiple sclerosis (MS). ON is an early diagnostic sign in most MS patients caused by damage to the optic nerve leading to visual dysfunction. Various features of both MS and ON can be studied following induction of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, in Lewis rats. Inflammation and cell death in the optic nerve, with subsequent damage to the retinal ganglion cells in the retina, are thought to correlate with visual dysfunction. Thus, characterizing the pathophysiological changes that lead to visual dysfunction in EAE animals may help develop novel targets for therapeutic intervention. We treated EAE animals with and without the calpain inhibitor calpeptin (CP). Our studies demonstrated that the Ca2+-activated neutral protease calpain was upregulated in the optic nerve following induction of EAE at the onset of clinical signs (OCS) of the disease and these changes were attenuated following treatment with CP. These reductions correlated with decreases in inflammation (cytokines, iNOS, COX-2, NF-κB), and microgliosis (i.e. activated microglia). We observed that calpain inhibition reduced astrogliosis (reactive astroglia) and expression of aquaporin 4 (AQP4). The balance of Th1/Th2 cytokine production and also expression of the Th1-related CCR5 and CXCR3 chemokine receptors influence many pathological processes and play both causative and protective roles in neuron damage. Our data indicated that CP suppressed cytokine imbalances. Also, Bax:Bcl-2 ratio, production of tBid, PARP-1, expression and activities of calpain and caspases, and internucleosomal DNA fragmentation were attenuated after treatment with CP. Our results demonstrated that CP decreased demyelination [loss of myelin basic protein (MBP)] and axonal damage [increase in dephosphorylated neurofilament protein (de-NFP), and also

  20. Acute effects of ethanol on hepatic uptake and distribution of narcotics in the isolated perfused rabbit liver

    Energy Technology Data Exchange (ETDEWEB)

    Kreek, M.J.; Rothschild, M.A.; Oratz, M.; Mongelli, J.; Handley, A.C.

    This study was performed as an initial step in systematically defining the hepatic interactions between ethanol and opioids using a controlled in vitro system. The acute effects of ethanol on the initial uptake and distribution of long- and short-acting narcotics were studied using isolated rabbit liver perfused with rabbit blood without or with ethanol. A pulse injection of 1.5 mg of 14C-labeled narcotic (methadone, 1-alpha-acetylmethadol (LAAM), morphine, or meperidine) was made into the portal vein cannula followed by perfusion for 2 min. Radioactivity was determined in liver homogenates and subcellular fractions; methadone and its metabolites were measured by thin-layer chromatography with zonal scanning in each fraction. Ethanol preperfusion and concomitant ethanol perfusion did not effect hepatic uptake of methadone, LAAM, morphine, or meperidine. Although subcellular localization of morphine and meperidine differed from that of methadone and LAAM, perfusion with ethanol did not alter the acute hepatic uptake and distribution of any of the narcotics. These findings suggest that acute exposure to ethanol does not alter the acute hepatic disposition of narcotics.

  1. Peginterferon-alfa mono-therapy in the treatment of acute hepatitis C in HIV-infection

    NARCIS (Netherlands)

    Boesecke, C.; van Assen, S.; Stellbrink, H. -J.; Baumgarten, A.; Ingiliz, P.; Strassburg, C. P.; Schwarze-Zander, C.; Wasmuth, J. -C.; Hoepelman, A. I. M.; Rockstroh, J. K.; Arends, J. E.

    2014-01-01

    The ongoing epidemic of acute hepatitis C (AHC) infection among MSM highlights the need to identify factors allowing for optimal treatment outcome in HIV co-infected individuals. Cohort study of 105 HIV-infected patients with AHC infection from five centres in two European countries was carried out.

  2. A 12-Week Treatment with Boceprevir, Peginterferon and Ribavirin for Acute Hepatitis C in HIV infected patients

    NARCIS (Netherlands)

    Hullegie, Sebastiaan J; Claassen, Mark A A; van den Berk, Guido E L; van der Meer, Jan T M; Posthouwer, Dirk; Lauw, Fanny N; Leyten, Eliane M S; Koopmans, Peter P; Richter, Clemens; van Eeden, Arne; Bierman, Wouter F W; Newsum, Astrid M; Arends, Joop E; Rijnders, Bart J A

    2016-01-01

    BACKGROUND AND AIMS: Acute hepatitis C virus infections (AHCV) are prevalent among HIV positive men having sex with men (MSM) and generally treated with peginterferon-alfa (pegIFN) and ribavirin (RBV) during 24 weeks. The addition of a protease inhibitor could shorten therapy without loss of efficac

  3. Intrahepatic Cholestasis of Pregnancy with Severe Elevation of Bile Acids in the Setting of Acute Hepatitis C Infection

    Directory of Open Access Journals (Sweden)

    Megan L. Lawlor

    2016-01-01

    Full Text Available Intrahepatic cholestasis of pregnancy (ICP is a complication of pregnancy resulting in elevation of serum bile acid levels. ICP is often associated with underlying liver disease, including hepatitis C. Bile acids in relationship to the acute infection of hepatitis C virus have not yet been delineated in the literature. A 26-year-old gravida 4 para 2103 with dichorionic, diamniotic twin gestation and history of intravenous drug abuse developed ICP in the setting of acute hepatitis C infection. In addition to clinical symptoms of pruritus and right upper quadrant pain, she developed severe elevation in bile acids, 239 micromol/L, and transaminitis aspartate aminotransferase 1033 U/L, and alanine aminotransferase 448 U/L. She received ursodeoxycholic acid and antenatal testing was performed. Patient delivered vaginally at 33-week gestation following preterm rupture of membranes. Neonates were admitted to NICU and had uncomplicated neonatal courses. In the setting of ICP with significant transaminitis and severe elevation of bile acids, consideration of acute viral hepatitis is important, especially considering the worsening opioid epidemic and concurrent increase in intravenous drug use in the United States. Further study is needed regarding the acute form of HCV infection and its effect on ICP and associated bile acids.

  4. Breviscapine attenuates acute pancreatitis by inhibiting expression of PKCα and NF-κB in pancreas

    Institute of Scientific and Technical Information of China (English)

    Hong Zhang; Cui-Zhu Cai; Xiao-Qin Zhang; Tao Li; Xiao-Yun Jia; Bao-Lan Li; Liang Song; Xiao-Jun Ma

    2011-01-01

    AIM: To study the effect of breviscapine (Bre) on activity of protein kinase Cα (PKCα) and nuclear factor (NF)-κB in pancreas, and the mechanism of Bre attenuating acute pancreatitis (AP).METHODS: One hundred and eight rats were randomly divided into acute necrotizing pancreatitis (ANP) group, Bre group (ANP + Bre group) and sham operation (SO) group, 36 rats in each group.ANP model was induced by a retrograde injection of 4% sodium deoxycholate into the bilio-pancreatic duct.Fifteen minutes after the ANP model was induced, the rats in Bre group were intraperitoneally injected with Bre (0.4 mg/100 g body weight or 0.1 mL/100 g body weight).Survival time and mortality of rats were calculated.Serum amylase and malondialdehyde levels were measured, volume of ascites was recorded and morphology of pancreas and lung was evaluated at 1, 5 and 10 h, after the ANP model was induced, respectively.Expressions of PKCα and subunit p65 of NF-κB in pancreas were detected by immunohistochemistry and Western blotting.RESULTS: The life span of rats was longer and the mortality was lower in Bre group than in ANP group 13.51 ± 5.46 vs 25.36 ± 8.11 (P < 0.05).The amylase and MDA levels as well as the volume of ascites were lower and the pathological changes in pancreas and lung were less in Bre group than ANP group (P < 0.05), indicating that the pancreatitis is less severe in Bre group than ANP group.The activation of PKCα and NF-κB p65 in pancreas was induced rapidly and reached their peak at 1 h or 5 h after ANP, but their activity in Bre group was significantly inhibited.CONCLUSION: Bre exerts its therapeutic effect on AP by inhibiting the activation of PKCα and NF-κB p65 in pancreas.

  5. Shikonin Attenuates Concanavalin A-Induced Acute Liver Injury in Mice via Inhibition of the JNK Pathway

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    Tong Liu

    2016-01-01

    Full Text Available Objective. Shikonin possesses anti-inflammatory effects. However, its function in concanavalin A-induced acute liver injury remains uncertain. The aim of the present study was to investigate the functions of shikonin and its mechanism of protection on ConA-induced acute liver injury. Materials and Methods. Balb/C mice were exposed to ConA (20 mg/kg via tail vein injection to establish acute liver injury; shikonin (7.5 mg/kg and 12.5 mg/kg was intraperitoneally administered 2 h before the ConA injection. The serum liver enzyme levels and the inflammatory cytokine levels were determined at 3, 6, and 24 h after ConA injection. Results. After the injection of ConA, inflammatory cytokines IL-1β, TNF-α, and IFN-γ were significantly increased. Shikonin significantly ameliorated liver injury and histopathological changes and suppressed the release of inflammatory cytokines. The expressions of Bcl-2 and Bax were markedly affected by shikonin pretreatment. LC3, Beclin-1, and p-JNK expression levels were decreased in the shikonin-pretreated groups compared with the ConA-treated groups. Shikonin attenuated ConA-induced liver injury by reducing apoptosis and autophagy through the inhibition of the JNK pathway. Conclusion. Our results indicated that shikonin pretreatment attenuates ConA-induced acute liver injury by inhibiting apoptosis and autophagy through the suppression of the JNK pathway.

  6. Pifithrin-μ Attenuates Acute Sickness Response to Lipopolysaccharide in C57BL/6J Mice.

    Science.gov (United States)

    Zhang, Rongping; Wang, Jili; Hu, Yanling; Lu, Xu; Jiang, Bo; Zhang, Wei; Huang, Chao

    2016-01-01

    Sickness behavior is a coordinated set of behavioral changes that happen as a response to acute infectious pathogens. Its well-known benefit is to reorganize the organism's priorities to cope with infection, but the uncontrolled development of sickness behavior may trigger negative feelings or chronic depressive events. This study aims at investigating the potential effect of pifithrin-μ, an inhibitor of heat shock protein 70 substrate binding activity, on lipopolysaccharide (LPS)-induced sickness response. C57BL/6J mice were submitted to the forced swimming test (FST), tail suspension test (TST), open field test (OFT) and light-dark box test. Food intake and body weight were also evaluated. The serum corticosterone level was measured using an ELISA kit. Treatment of mice with LPS (0.33 mg/kg, i.p.) markedly increased the floating and immobility time in the FST and TST, respectively, and depressed locomotor activity in the OFT. LPS administration prolonged the latency to first transition and reduced the total number of transitions in the light-dark box test. In addition, LPS induced anorexia and increased serum corticosterone levels. Pretreatment with pifithrin-μ (1 or 5 mg/kg) attenuated behavioral changes induced by LPS in the FST, TST, OFT and light-dark box test. Pifithrin-μ also prevented the formation of anorexia as well as the increase in serum corticosterone levels in LPS-treated mice. Our previous studies showed that pifithrin-μ prevents the production of pro-inflammatory factors in both microglia and macrophages. These findings presented here extend the role of pifithrin-μ beyond an anti-inflammatory molecule to a modulator of sickness behavior.

  7. Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid.

    Science.gov (United States)

    Fisher, Bernard J; Kraskauskas, Donatas; Martin, Erika J; Farkas, Daniela; Wegelin, Jacob A; Brophy, Donald; Ward, Kevin R; Voelkel, Norbert F; Fowler, Alpha A; Natarajan, Ramesh

    2012-07-01

    Bacterial infections of the lungs and abdomen are among the most common causes of sepsis. Abdominal peritonitis often results in acute lung injury (ALI). Recent reports demonstrate a potential benefit of parenteral vitamin C [ascorbic acid (AscA)] in the pathogenesis of sepsis. Therefore we examined the mechanisms of vitamin C supplementation in the setting of abdominal peritonitis-mediated ALI. We hypothesized that vitamin C supplementation would protect lungs by restoring alveolar epithelial barrier integrity and preventing sepsis-associated coagulopathy. Male C57BL/6 mice were intraperitoneally injected with a fecal stem solution to induce abdominal peritonitis (FIP) 30 min prior to receiving either AscA (200 mg/kg) or dehydroascorbic acid (200 mg/kg). Variables examined included survival, extent of ALI, pulmonary inflammatory markers (myeloperoxidase, chemokines), bronchoalveolar epithelial permeability, alveolar fluid clearance, epithelial ion channel, and pump expression (aquaporin 5, cystic fibrosis transmembrane conductance regulator, epithelial sodium channel, and Na(+)-K(+)-ATPase), tight junction protein expression (claudins, occludins, zona occludens), cytoskeletal rearrangements (F-actin polymerization), and coagulation parameters (thromboelastography, pro- and anticoagulants, fibrinolysis mediators) of septic blood. FIP-mediated ALI was characterized by compromised lung epithelial permeability, reduced alveolar fluid clearance, pulmonary inflammation and neutrophil sequestration, coagulation abnormalities, and increased mortality. Parenteral vitamin C infusion protected mice from the deleterious consequences of sepsis by multiple mechanisms, including attenuation of the proinflammatory response, enhancement of epithelial barrier function, increasing alveolar fluid clearance, and prevention of sepsis-associated coagulation abnormalities. Parenteral vitamin C may potentially have a role in the management of sepsis and ALI associated with sepsis.

  8. CAFFEINE ATTENUATES ACUTE GROWTH HORMONE RESPONSE TO A SINGLE BOUT OF RESISTANCE EXERCISE

    Directory of Open Access Journals (Sweden)

    Bo-Hun Wu

    2010-06-01

    Full Text Available The purpose of this study was to investigate the effects of caffeine consume on substrate metabolism and acute hormonal responses to a single bout of resistance exercise (RE. Ten resistance-trained men participated in this study. All subjects performed one repetition maximum (1RM test and then performed two protocols: caffeine (CAF, 6 mg·kg-1 and control (CON in counter balanced order. Subjects performed RE (8 exercises, 3 sets of 10 repetitions at 75% of 1RM after caffeine or placebo ingestion one hour prior to RE. Blood samples collected prior to treatment ingestion (pre-60, immediately prior to RE (pre-exe, and 0, 15, 30 min post to RE (P0, P15, P30 for analysis of insulin, testosterone, cortisol, growth hormone, glucose, free fatty acid and lactic acid. Each experiment was separated by seven days. In this study, statistical analysis of a two-way analysis of variance (treatment by time with repeated measures was applied. After ingesting caffeine, the concentrations of free fatty acid (pre- exe, P0, P15, P30 in CAF were significantly higher than CON (p < 0.05. Additionally, the responses of GH (P0, P15, P30 in CAF were significantly lower than CON (p < 0.05, whereas the concentrations of insulin, testosterone and cortisol were not different between CAF and CON (p < 0.05 after RE. The results of this study indicated that caffeine ingestion prior to RE might attenuate the response of GH. This effect might be caused by the elevation in blood FFA concentration at the beginning of RE

  9. Involvement of the TNF and FasL produced by CD11b Kupffer cells/macrophages in CCl4-induced acute hepatic injury.

    Directory of Open Access Journals (Sweden)

    Atsushi Sato

    Full Text Available We previously reported that F4/80(+ Kupffer cells are subclassified into CD68(+ Kupffer cells with phagocytic and ROS producing capacity, and CD11b(+ Kupffer cells with cytokine-producing capacity. Carbon tetrachloride (CCl4-induced hepatic injury is a well-known chemical-induced hepatocyte injury. In the present study, we investigated the immunological role of Kupffer cells/macrophages in CCl4-induced hepatitis in mice. The immunohistochemical analysis of the liver and the flow cytometry of the liver mononuclear cells showed that clodronate liposome (c-lipo treatment greatly decreased the spindle-shaped F4/80(+ or CD68(+ cells, while the oval-shaped F4/80+ CD11b(+ cells increased. Notably, severe hepatic injury induced by CCl4 was further aggravated by c-lipo-pretreatment. The population of CD11b(+ Kupffer cells/macrophages dramatically increased 24 hour (h after CCl4 administration, especially in c-lipo-pretreated mice. The CD11b(+ Kupffer cells expressed intracellular TNF and surface Fas-ligand (FasL. Furthermore, anti-TNF Ab pretreatment (which decreased the FasL expression of CD11b(+ Kupffer cells, anti-FasL Ab pretreatment or gld/gld mice attenuated the liver injury induced by CCl4. CD1d-/- mouse and cell depletion experiments showed that NKT cells and NK cells were not involved in the hepatic injury. The adoptive transfer and cytotoxic assay against primary cultured hepatocytes confirmed the role of CD11b(+ Kupffer cells in CCl4-induced hepatitis. Interestingly, the serum MCP-1 level rapidly increased and peaked at six h after c-lipo pretreatment, suggesting that the MCP-1 produced by c-lipo-phagocytized CD68(+ Kupffer cells may recruit CD11b(+ macrophages from the periphery and bone marrow. The CD11b(+ Kupffer cells producing TNF and FasL thus play a pivotal role in CCl4-induced acute hepatic injury.

  10. Patterns of hepatitis C virus RNA levels during acute infection: the InC3 study.

    Directory of Open Access Journals (Sweden)

    Behzad Hajarizadeh

    Full Text Available Understanding the patterns of HCV RNA levels during acute hepatitis C virus (HCV infection provides insights into immunopathogenesis and is important for vaccine design. This study evaluated patterns of HCV RNA levels and associated factors among individuals with acute infection.Data were from an international collaboration of nine prospective cohorts of acute HCV (InC3 Study. Participants with well-characterized acute HCV infection (detected within three months post-infection and interval between the peak and subsequent HCV RNA levels ≤ 120 days were categorised by a priori-defined patterns of HCV RNA levels: i spontaneous clearance, ii partial viral control with persistence (≥ 1 log IU/mL decline in HCV RNA levels following peak and iii viral plateau with persistence (increase or <1 log IU/mL decline in HCV RNA levels following peak. Factors associated with HCV RNA patterns were assessed using multinomial logistic regression.Among 643 individuals with acute HCV, 162 with well-characterized acute HCV were identified: spontaneous clearance (32%, partial viral control with persistence (27%, and viral plateau with persistence (41%. HCV RNA levels reached a high viraemic phase within two months following infection, with higher levels in the spontaneous clearance and partial viral control groups, compared to the viral plateau group (median: 6.0, 6.2, 5.3 log IU/mL, respectively; P = 0.018. In the two groups with persistence, Interferon lambda 3 (IFNL3 CC genotype was independently associated with partial viral control compared to viral plateau (adjusted odds ratio [AOR]: 2.75; 95%CI: 1.08, 7.02. In the two groups with viral control, female sex was independently associated with spontaneous clearance compared to partial viral control (AOR: 2.86; 95%CI: 1.04, 7.83.Among individuals with acute HCV, a spectrum of HCV RNA patterns is evident. IFNL3 CC genotype is associated with initial viral control, while female sex is associated with ultimate

  11. Quercetin Attenuates Chronic Ethanol-Induced Hepatic Mitochondrial Damage through Enhanced Mitophagy.

    Science.gov (United States)

    Yu, Xiao; Xu, Yanyan; Zhang, Shanshan; Sun, Jian; Liu, Peiyi; Xiao, Lin; Tang, Yuhan; Liu, Liegang; Yao, Ping

    2016-01-05

    Emerging evidence suggested mitophagy activation mitigates ethanol-induced liver injury. However, the effect of ethanol on mitophagy is inconsistent. Importantly, the understanding of mitophagy status after chronic ethanol consumption is limited. This study evaluated the effect of quercetin, a naturally-occurring flavonoid, on chronic ethanol-induced mitochondrial damage focused on mitophagy. An ethanol regime to mice for 15 weeks (accounting for 30% of total calories) led to significant mitochondrial damage as evidenced by changes of the mitochondrial ultrastructure, loss of mitochondrial membrane potential and remodeling of membrane lipid composition, which was greatly attenuated by quercetin (100 mg/kg.bw). Moreover, quercetin blocked chronic ethanol-induced mitophagy suppression as denoted by mitophagosomes-lysosome fusion and mitophagy-related regulator elements, including LC3II, Parkin, p62 and voltage-dependent anion channel 1 (VDAC1), paralleling with increased FoxO3a nuclear translocation. AMP-activated protein kinase (AMPK) and extracellular signal regulated kinase 2 (ERK2), instead of AKT and Sirtuin 1, were involved in quercetin-mediated mitophagy activation. Quercetin alleviated ethanol-elicited mitochondrial damage through enhancing mitophagy, highlighting a promising preventive strategy for alcoholic liver disease.

  12. Connective tissue growth factor hammerhead ribozyme attenuates human hepatic stellate cell function

    Institute of Scientific and Technical Information of China (English)

    Run-Ping Gao; David R Brigstock

    2009-01-01

    AIM: To determine the effect of hammerhead ribozyme targeting connective tissue growth factor (CCN2) on human hepatic stellate cell (HSC) function. METHODS: CCN2 hammerhead ribozyme cDNA plus two self-cleaving sequences were inserted into pTriEx2 to produce pTriCCN2-Rz. Each vector was individually transfected into cultured LX-2 human HSCs, which were then stimulated by addition of transforming growth factor (TGF)-b1 to the culture medium. Semiquantitative RT-PCR was used to determine mRNA levels for CCN2 or collagen Ⅰ, while protein levels of each molecule in cell lysates and conditioned medium were measured by ELISA. Cell-cycle progression of the transfected cells was assessed by flow cytometry. RESULTS: In pTriEx2-transfected LX-2 cells, TGF-β1 treatment caused an increase in the mRNA level for CCN2 or collagen Ⅰ, and an increase in produced and secreted CCN2 or extracellular collagen Ⅰ protein levels. pTriCCN2-Rz-transfected LX-2 cells showed decreased basal CCN2 or collagen mRNA levels, as well as produced and secreted CCN2 or collagen Ⅰ protein. Furthermore, the TGF-b1-induced increase in mRNA or protein for CCN2 or collagen Ⅰ was inhibited partially in pTriCCN2-Rz-transfected LX-2 cells. Inhibition of CCN2 using hammerhead ribozyme cDNA resulted in fewer of the cells transitioning into S phase. CONCLUSION: Endogenous CCN2 is a mediator of basal or TGF-b1-induced collagen Ⅰ production in human HSCs and regulates entry of the cells into Sphase.

  13. (Toxic hepatitis and acute renal failure after inhalation of chloride solvents: report of one case (author's transl))

    Energy Technology Data Exchange (ETDEWEB)

    Teixido Planas, J.; Martinez-Castelao, A.; Romero Gonzalez, R.; Grino Boira, J.; Gonzalez Segura, C.; Caralps Riera, A.

    1981-06-25

    Due to a combination of ingested ethanol and inhaled trichloroethylene (Tri) a 28 year old man developed toxic hepatitis and acute oliguric renal failure, both of which had a favorable evolution. Tri has been described as a cause of hepatic disfunction and acute renal failure due to acute tubular necrosis, although some of the cases described are controversial, because Tri was either contaminated by other dissolvents or could not be proven pure, with the exception of one case. In many there was ethanol ingestion. The Tri inhaled by our patient was found to contain less than 1% of carbon tetrachloride (C-Tchl). This would suggest the C-Tchl to be responsible for the clinical picture although the combination Tri/ethanol cannot be discarded as the causal agent, due to the small amount of contaminant present.

  14. A Case of Acute Q Fever Hepatitis Diagnosed by F-18 FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Beak, Sora [Hallym Univ. College of Medicine, Seoul (Korea, Republic of); Oh, Minyoung; Lee, Sand-Oh; Yu, Eunsil; Ryu Jin-Sook [Univ. of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2012-06-15

    A 53-year-old man with fever of unknown origin underwent F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) as a workup for a fever of unknown origin. On presentation, he complained of fever, chills, and myalgia. The F-18 FDG PET/CT scan showed diffusely increased uptake of the liver with mild hepatomegaly. A liver biopsy then revealed fibrin-ring granulomas typically seen in Q fever. The patient was later serologically diagnosed as having acute Q fever as the titers for C. IgM and IgG were 64:1 and -16:1, respectively. He recovered completely following administration of doxycycline. This indicates that F-18 FDG PET/CT may be helpful for identifying hepatic involvement in Q fever as a cause of fever of unknown origin.

  15. Liver transplantation for acute hepatic failure due to chemotherapy-induced HBV reactivation in lymphoma patients

    Institute of Scientific and Technical Information of China (English)

    Timothée Noterdaeme; Luc Longrée; Christian Bataille; Arnaud Deroover; Anne Lamproye; Jean Delwaide; Yves Beguin; Pierre Honoré; Olivier Detry

    2011-01-01

    Hepatitis B (HBV) reactivation induced by chemotherapy is problem encountered recently in the management of malignant diseases. Chemotherapy-induced HBV reactivation may ultimately lead to terminal acute liver failure. Liver transplantation (LT) currently remains the only definitive treatment option for such cases, but is generally denied to patients suffering from malignancy. Here, the authors describe 2 cases of cancer-free and HBV graft re-infection-free survival after LT performed for terminal liver failure arising from HBV reactivation induced by chemotherapy for advanced stage lymphoma. These 2 cases, and some other reports in the literature, may suggest that patients suffering from hematologic malignancies and terminal liver disease can be considered for LT if the prognosis of their hematologic malignancy is good.

  16. Pure red-cell aplasia and autoimmune hemolytic anemia in a patient with acute hepatitis A.

    Science.gov (United States)

    Chang, Hyo Jeong; Sinn, Dong Hyun; Cho, Sung Gyun; Oh, Tae Hoon; Jeon, Tae Joo; Shin, Won Chang; Choi, Won Choong

    2014-06-01

    Pure red cell aplasia (PRCA) and autoimmune hemolytic anemia (AIHA) have rarely been reported as an extrahepatic manifestation of acute hepatitis A (AHA). We report herein a case of AHA complicated by both PRCA and AIHA. A 49-year-old female with a diagnosis of AHA presented with severe anemia (hemoglobin level, 6.9 g/dL) during her clinical course. A diagnostic workup revealed AIHA and PRCA as the cause of the anemia. The patient was treated with an initial transfusion and corticosteroid therapy. Her anemia and liver function test were completely recovered by 9 months after the initial presentation. We review the clinical features and therapeutic strategies for this rare case of extrahepatic manifestation of AHA.

  17. Changes of hepatic lactoferrin gene expression in two mouse models of the acute phase reaction.

    Science.gov (United States)

    Ahmad, Ghayyor; Sial, Gull Zareen Khan; Ramadori, Pierluigi; Dudas, Jozsef; Batusic, Danko S; Ramadori, Giuliano

    2011-12-01

    Lactoferrin (Ltf), an iron binding glycoprotein, is a pleiotropic molecule whose serum concentration increases under acute phase conditions. The physiological roles of this protein have been well elucidated, but the source and serum regulation of Ltf gene expression have not been investigated in detail as part of the acute phase reaction (APR). In the current work, the changes in hepatic Ltf-gene-expression during turpentine oil- (TO-) or LPS-induced APR were investigated. Ltf was upregulated at both the mRNA and protein levels in the liver of TO- and LPS-treated wild type (WT) mice. The pattern of induction however was different in both animal models indicating distinctive signalling patterns resulting in an acute phase reaction. Cytokines are the core regulators of APR. Among the major cytokines, IL-6 is an important signalling molecule, which also regulates iron homeostasis in response to an inflammatory situation. In this study, the administration of IL-6 induced Ltf gene expression in the liver of WT mice, in murine hepatocytes and in hepa 1-6 cells. Ltf-gene-expression was upregulated also in the liver of TO- and LPS-treated IL-6 knockout (KO) mice. The increase in serum Ltf after LPS injection was greater than after TO-injection both in WT and IL-6-KO mice. To evaluate the contribution of other acute phase cytokines in the regulation of Ltf-gene-expression in the liver, both in vitro and in vivo studies with IL-1β, TNF-α, or IFN-γ were performed. The results demonstrate that TNF-α and IFN-γ also upregulated Ltf-gene-expression, while IL-1β has no role in the regulation of Ltf-gene-expression.

  18. Acute Sickle Hepatic Crisis after Liver Transplantation in a Patient with Hb SC Disease

    Directory of Open Access Journals (Sweden)

    J. H. Gillis

    2015-01-01

    Full Text Available Acute sickle hepatic crisis (ASHC has been observed in approximately 10% of patients with sickle cell disease. It occurs predominantly in patients with homozygous (Hb SS sickle cell anemia and to a lesser degree in patients with Hb SC disease, sickle cell trait, and Hb S beta thalassemia. Patients commonly present with jaundice, right upper quadrant pain, nausea, low-grade fever, tender hepatomegaly, and mild to moderate elevations in serum AST, ALT, and bilirubin. We describe the case of a patient with a history of hemoglobin SC disease and cirrhosis caused by hepatitis C presenting approximately 1 year after liver transplantation with an ASHC. The diagnosis was confirmed by liver biopsy. Our patient was treated with RBC exchange transfusions, IV hydration, and analgesia and made a complete recovery. Only a limited number of patients with sickle cell disease have received liver transplants, and, to our knowledge, this is the first case of ASHC after transplantation in a patient with Hb SC disease.

  19. Survival and prognostic factors in hepatitis B virus-related acute-on-chronic liver failure

    Institute of Scientific and Technical Information of China (English)

    Kun Huang; Jin-Hua Hu; Hui-Fen Wang; Wei-Ping He; Jing Chen; Xue-Zhang Duan; Ai-Min Zhang; Xiao-Yan Liu

    2011-01-01

    AIM: To investigate the survival rates and prognostic ffactors in patients with hepatitis B virus-related acute-on-chronic liver ffailure (HBV-ACLF).METHODS: Clinical data in hospitalized patients with HBV-ACLF admitted ffrom 2006 to 2009 were retrospectively analyzed. Their general conditions and survival were analyzed by survival analysis and Cox regression analysis.RESULTS: A total off 190 patients were included in this study. The overall 1-year survival rate was 57.6%. Patients not treated with antiviral drugs had a significantly higher mortality [relative risk (RR) = 0.609, P = 0.014].The highest risk off death in patients with ACLF was associated with hepatorenal syndrome (HRS) (RR = 2.084, P =0.026), while other significant factors were electrolyte disturbances (RR = 2.062, P = 0.010), and hepatic encephalopathy (HE) (RR = 1.879, P < 0.001).CONCLUSION: Antiviral therapy has a strong effffect on the prognosis off the patients with HBV-ACLF by improving their 1-year survival rate. HRS, electrolyte disturbances,and HE also affffect patient survival.

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

    Institute of Scientific and Technical Information of China (English)

    María Jesús Tu(n)ón; Marcelino Alvarez; Jesús M Culebras; Javier González-Gallego

    2009-01-01

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

  1. Ciclosporin does not attenuate intracranial hypertension in rats with acute hyperammonaemia

    DEFF Research Database (Denmark)

    Larsen, Rikke Hebo; Kjær, Mette S; Eefsen, Martin;

    2013-01-01

    To investigate the neuroprotective potential of ciclosporin during acute liver failure. We evaluated the effect of intrathecally administered ciclosporin on intracranial pressure, brain water content and aquaporin-4 expression in a rat model with acute hyperammonaemia....

  2. Rosiglitazone, a PPAR-γ agonist, fails to attenuate CLA-induced milk fat depression and hepatic lipid accumulation in lactating mice.

    Science.gov (United States)

    Vyas, Diwakar; Teter, Beverly B; Delmonte, Pierluigi; Erdman, Richard A

    2014-07-01

    Our objective was to investigate the combination of rosiglitazone (ROSI) and conjugated linoleic acid (CLA) on mammary and hepatic lipogenesis in lactating C57Bl/6 J mice. Twenty-four lactating mice were randomly assigned to one of four treatments applied from postpartum day 6 to day 10. Treatments included: (1) control diet, (2) control plus 1.5 % dietary CLA (CLA) substituted for soybean oil, (3) control plus daily intra-peritoneal (IP) rosiglitazone injections (10 mg/kg body weight) (ROSI), and (4) CLA plus ROSI (CLA-ROSI). Dam food intake and milk fat concentration were depressed with CLA. However, no effects were observed with ROSI. The CLA-induced milk fat depression was due to reduced expression for mammary lipogenic genes involved in de-novo fatty acid (FA) synthesis, FA uptake and desaturation, and triacyglycerol synthesis. Liver weight (g/100 g body weight) was increased by CLA due to an increase in lipid accumulation triggering a compensatory reduction in mRNA abundance of hepatic lipogenic enzymes, including acetyl-CoA carboxylase I and stearoyl-CoA desaturase I. On the contrary, no effects were observed with ROSI on hepatic and mammary lipogenic gene and enzyme expression. Overall, feeding CLA to lactating mice induced milk fat depression and increased hepatic lipid accumulation, probably due to the presence of trans-10, cis-12 CLA isomer, while ROSI failed to significantly attenuate both hepatic steatosis and reduction in milk fat content.

  3. Wortmannin, PI3K/Akt signaling pathway inhibitor, attenuates thyroid injury associated with severe acute pancreatitis in rats.

    Science.gov (United States)

    Abliz, Ablikim; Deng, Wenhong; Sun, Rongze; Guo, Wenyi; Zhao, Liang; Wang, Weixing

    2015-01-01

    Increasing evidences suggest that PI3K/AKT pathway plays an important role in the pathogenesis of inflammatory diseases such as acute pancreatitis. However, the exact effect of PI3K/AKT on thyroid injury associated with acute pancreatitis has not been investigated. This study aimed to investigate the protective effects of wortmannin, PI3K/AKT inhibitor, on thyroid injury in a rat model of severe acute pancreatitis (SAP). Sixty male SD rats were randomly divided into four groups: sham operating group (SO), SAP group, wortmannin treatment (WOR) group and drug control (WOR-CON) group. Serum amylase (AMY), lipase (LIP) and thyroid hormone levels were evaluated. The morphological change of thyroid tissue was analyzed under the light and transmission electron microscopy. AKT, P38MAPK and NF-κB expression in the thyroid tissue was evaluated by immunohistochemical staining. Oxidative stress and inflammatory cytokines were detected. Results showed that wortmannin attenuated the following: (1) serum AMY, LIP and thyroid hormone (2) pancreatic and thyroid pathological injuries (3) thyroid MDA, (4) thyroid ultrastructural change, (5) serum TNF-α, IL-6 and IL-1β (6) AKT, MAPKP38 and NF-κB expression in thyroid tissues. These results suggested that wortmannin attenuates thyroid injury in SAP rats, presumably because of its role on prevent ROS generation and inhibits the activation of P38MAPK, NF-κB pathway. Our findings provide new therapeutic targets for thyroid injury associated with SAP.

  4. IkB kinase-beta inhibitor attenuates hepatic fibrosis in mice

    Institute of Scientific and Technical Information of China (English)

    Jue Wei; Min Shi; Wei Qi Wu; Ting Wang; Na Wang; Jia-Li Ma; Yu-Gang Wang

    2011-01-01

    AIM: To investigate the anti-fibrosis effect of IκkB kinase-beta inhibitor (IKK2 inhibitor IMD0354) in liver fibrosis. METHODS: Twenty male C57BL6 mice were divided into four groups. Five high-fat fed mice were injected with lipopolysaccharide (LPS, 10 mg/kg) intraperitoneally and five high-fat fed mice were without LPS injection to build models of liver injury, and the intervention group (five mice) was injected intraperitoneally with IKK2 inhibitor (IMD 30 mg/kg for 14 d), while the remaining five mice received a normal diet as controls. Hepatic function, pathological evaluation and liver interleukin- 6 (IL-6) expression were examined. Western blotting and real-time polymerase chain reaction were used to detect the expressions of nuclear factor-κkB (NF-κkB), alpha-smooth muscle actin (α-SMA), tumor growth factor-beta1 (TGF-β1), tumor necrosis factor-alpha (TNF-α), typeⅠand type Ⅲ collagen proteins and mRNA. RESULTS: A mouse model of liver injury was successfully established, and IMD decreased nuclear translocation translocation of NF-κkB p65 in liver cells. In the IMD-treated group, the levels of alanine aminotransferase (103 ± 9.77 μ/L vs 62.4 ± 7.90 μ/L, P < 0.05) and aminotransferase (295.8 ± 38.56 μ/L vs 212 ± 25.10 μ/L, P < 0.05) were significantly decreased when compared with the model groups. The histological changes were significantly ameliorated. After treatment, the expressions of IL-6 (681 ± 45.96 vs 77 ± 7.79, P < 0.05), TGF-β1 (Western blotting 5.65% ± 0.017% vs 2.73% ± 0.005%, P < 0.05), TNF-α (11.58% ± 0.0063% vs 8.86% ± 0.0050%, P < 0.05), typeⅠcollagen (4.49% ± 0.014% vs 1.90% ± 0.0006%, P < 0.05) and type Ⅲ collagen (3.46% ± 0.008% vs 2.29% ± 0.0035%, P < 0.05) as well as α-SMA (6.19 ± 0.0036 μ/L vs 2.16 ± 0.0023 μ/L, P < 0.05) protein and mRNA were downregulated in the IMD group compared to the fibrosis control groups (P < 0.05).CONCLUSION: IKK2 inhibitor IMD markedly improved non-alcoholic fatty liver

  5. Efficacy of liver transplantation for acute hepatic failure:a single-center experience

    Institute of Scientific and Technical Information of China (English)

    Xian-Jie Shi; Hong-Bin Xu; Wen-Bin Ji; Yu-Rong Liang; Wei-Dong Duan; Lei He; Ming-Jun Wang; Zhi-Ming Zhao

    2011-01-01

    BACKGROUND: Acute hepatic failure (AHF) is a devastating clinical syndrome with a high mortality rate. The outcome of AHF varies with etiology, but liver transplantation (LT) can significantly improve the prognosis and survival rate of such patients. This study aimed to detect the role of LT and artificial liver support systems (ALSS) for AHF patients and to analyze the etiology and outcome of patients with this disease. METHODS: A retrospective analysis was made of 48 consecutive patients with AHF who fulfilled the Kings College Criteria for LT at our center. We analyzed and compared the etiology, outcome, prognosis, and survival rates of patients between the transplantation (LT) group and the non-transplantation (N-LT) group. RESULTS: AHF was due to viral hepatitis in 25 patients (52.1%; hepatitis B virus in 22), drug or toxic reactions in 14 (29.2%; acetaminophen in 6), Wilson disease in 4 (8.3%), unknown reasons in 3 (6.3%), and miscellaneous conditions in 2 (4.2%). In the LT group, 36 patients (7 underwent living donor LT, and 29 cadaveric LT) had an average model for end-stage liver disease score (MELD) of 35.7. Twenty-eight patients survived with good graft function after a follow-up of 27.3± 4.5 months. During the waiting time, 6 patients were treated with ALSS and 2 of them died during hospitalization. The 30-day, 12-month, and 18-month survival rates were 77.8%, 72.2%, and 66.7%, respectively. In the N-LT group, 12 patients had an average MELD score of 34.5. Four patients were treated with ALSS and all died during hospitalization. The 90-day and 1-year survival rates were only 16.7% and 8.3%, respectively. CONCLUSIONS: Hepatitis is the most prominent cause of AHF at our center. Most patients with AHF, who fulfill the Kings College Criteria for LT, did not survive longer without LT. ALSS did not improve the prognosis of AHF patients, but may extend the waiting time for a donor. Currently, LT is still the most effective way to improve the prognosis

  6. Attenuation of hypoxic pulmonary vasoconstriction in acute oleic acid lung injury--significance of vasodilator prostanoids.

    Science.gov (United States)

    Yamaguchi, K; Mori, M; Kawai, A; Asano, K; Takasugi, T; Umeda, A; Yokoyama, T

    1992-01-01

    To assess a significant role of hypoxic pulmonary vasoconstriction, HPV, on maintaining the gas exchange efficiency in acute lung injury, 24 mongrel dogs were treated with intravenously injecting 0.07 ml/kg of oleic acid. Hemodynamic and gas-exchange parameters were investigated at varied inspired O2 concentration, FIO2. To know a possible contribution of vasoactive prostanoids in regulating vascular reactivity under these circumstances, observations were repeated after infusion of indomethacin. The impairment of gas exchange in injured lungs was examined by measuring the fractional retention, R, of the gas in arterial blood. For this evaluation, a normal saline containing five foreign inert gases such as sulfur hexafluoride, SF6, ethane, cyclopropane, halothane and diethyl ether was infused at a constant rate through a peripheral vein. After a steady state was established, the expired gas was collected and the samples of both arterial and mixed venous blood were simultaneously taken for the inert-gas analysis. The concentrations of the indicator gases in the samples were measured in terms of a gas chromatograph equipped with an electron capture detector for SF6 and a flame ionization detector for the other four gases. Although pulmonary vascular resistance, PVR, after injecting oleic acid at FIO2 0.60 was significantly smaller than that obtained at FIO2 0.21, cardiac output, QT as well as extravascular lung water were not different between the two conditions. R value for the indicator gas was consistently lower at FIO2 0.60 irrespective of the gas species. As increasing FIO2, R estimate concerning SF6, RSF6, rational index of the fractional blood flow perfusing shunt area, decreased significantly. Administration of indomethacin caused the rise in PVR without an appreciable change in either QT or extravascular lung water but a considerable diminution in R value for the inert gas. RSF6 after infusion of indomethacin decreased from 0.35 to 0.27, accompanied by a

  7. INTERRELATIONS BETWEEN IMMUNOLOGICAL ALTERATIONS AND VIRAL LOAD IN ACUTE HEPATITIS B

    Directory of Open Access Journals (Sweden)

    A. A. Savchenko

    2011-01-01

    Full Text Available Abstract. A group of seventy-six patients with acute viral hepatitis B (HB was under study, in order to evaluate immunological parameters, and ability of blood mononuclear cells to produce cytokines, as dependent on individual viral loads. The immune parameters were less affected in cases of low viral load. Meanwhile, the immune profiles exhibited maximal alterations in the patients with medium and high viral loads. Most expressed changes of immune parameters are found in patients with moderate and high  virus load. Meanwhile, moderate  HB  viral  loads  are  associated  with  higher  functional  activity  of  B-cells  and  lower  NK  numbers, whereas high viral loads correlated with increased amounts of peripheral B cells and higher CD25+ lymphocyte levels. Increased background cytokine synthesis is revealed in mononuclear cells of the patients with acute HB, being, however, suppressed upon additional functional induction. An increased viral load is associated with decreased basal levels of TNFα synthesis. (Med. Immunol., 2011, vol. 13, N 2-3, pp 181-188 

  8. Immune complexed (IC) hepatitis C virus (HCV) in chronically and acutely HCV-infected patients.

    Science.gov (United States)

    Riva, E; Maggi, F; Abbruzzese, F; Bellomi, F; Giannelli, G; Picardi, A; Scagnolari, C; Folgori, A; Spada, E; Piccolella, E; Dianzani, F; Antonelli, G

    2009-02-01

    In infected individuals, hepatitis C virus (HCV) exists in various forms of circulating particles which role in virus persistence and in HCV resistance to IFN therapy is still debated. Here, the proportion of HCV bound to immunoglobulin was determined in plasma of 107 chronically infected patients harbouring different HCV genotypes and, for comparison, of six patients with acute HCV infection. The results showed that, in spite of wide individual variability, chronically HCV-infected patients exhibited an extremely high proportion of immune complexed (IC) virus regardless of plasma HCV load and infecting genotype. Moreover, no significant association was found between baseline proportion of IC HCV and response to IFN treatment. Plasma samples collected within 2 weeks of treatment from 20 patients revealed a significant decline of mean IC HCV values relative to baseline that clearly paralleled the decay of total HCV load. In acutely infected patients, circulating HCV was not IC or IC at very low levels only in patients developing chronic HCV infection. Collectively, these findings strengthen the possibility that IC virus could play a critical role in the pathogenesis of HCV infection.

  9. Interstitial nephritis, acute renal failure in a patient with non-fulminant hepatitis A infection.

    Science.gov (United States)

    Vaboe, A L; Leh, S; Forslund, T

    2002-02-01

    This is the first report from Norway of a patient with interstitial nephritis and renal failure due to non-fulminant hepatitis A virus (HAV) infection. HAV infection was confirmed by positive anti-HAV IgM serology. All tests for other virus infections were negative. At admittance serum creatinine (s-Creat) and blood urea nitrogen (BUN) concentration were 539 microlmol/l and 32.6 mmol/l increasing the following days to 890 micromol/l and 39.9 mmol/l, respectively. Nine courses of hemodialysis had to be given. Kidney biopsy specimen showed interstitial edema, lymphocytic cell infiltration and acute tubular injury with normal glomeruli. Examination with immunohistochemistry was negative. In contrast to the findings associated with HBV and HCV infection in which glomerular disease is predominantly found, the HAV infection in our patient was associated with interstitial nephritis and acute tubular necrosis. The prognosis of the renal failure due to HAV infection was good although the recovery was substantially delayed.

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

    Science.gov (United States)

    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

  11. Pioglitazone attenuates the severity of sodium taurocholate-induced severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Ping Xu; Xiao-Jiang Zhou; Ling-Quan Chen; Jiang Chen; Yong Xie; Long-Hua Lv; Xiao-Hua Hou

    2007-01-01

    AIM: To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-γ (PPARγ)ligand, on development of severe acute pancreatitis (SAP) and expression of nuclear factor-kappa B (NF-κB)and intercellular adhesion molecule-1 (ICAM-1) in the pancreas.METHODS: Male Sprague-Dawley (SD) rats (160-200 g)were randomly allocated into three groups (n = 18in each group): severe acute pancreatitis group,pioglitazone group, sham group. SAP was induced by retrograde infusion of 1 mL/kg body weight 5% sodium taurocholate (STC) into the biliopancreatic duct of male SD rats. Pioglitazone was injected intraperitoneally two hours piror to STC infusion. Blood and ascites were obtained for detecting amylase and ascitic capacity. Pancreatic wet/dry weight ratio, expression of NF-κB and ICAM-1 in pancreatic tissues were detected by immunohistochemical staining. Pancreatic tissue samples were stained with hematoxylin and eosin (HE)for routine optic microscopy.RESULTS: Sham group displayed normal pancreatic structure. SAP group showed diffuse hemorrhage,necrosis and severe edema in focal areas of pancreas.There was obvious adipo-saponification in abdominal cavity. Characteristics such as pancreatic hemorrhage,necrosis, severe edema and adipo-saponification were found in pioglitazone group, but the levels of those injuries were lower in pioglitazone group than those in SAP group. The wet/dry pancreatic weight ratio,ascetic capacity, serum and ascitic activities of anylase in the SAP group were significantly higher than those in the sham group and pioglitazone group respectively (6969.50 ± 1368.99 vs 2104.67 ± 377.16, 3.99 ± 1.22 vs 2.48 ± 0.74, P < 0.01 or P < 0.05). According to Kusske criteria, the pancreatic histologic score showed that interstitial edema, inflammatory infiltration,parenchyma necrosis and parenchyma hommorrhage in SAP group significantly differed from those in the sham group and pioglitazone group (7.17 ± 1.83 vs 0.50 ±0.55, 7

  12. Adenoviral overexpression of Lhx2 attenuates cell viability but does not preserve the stem cell like phenotype of hepatic stellate cells

    Energy Technology Data Exchange (ETDEWEB)

    Genz, Berit [Institute for Experimental Surgery, Rostock University Medical Center, Rostock (Germany); Thomas, Maria [Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart (Germany); Pützer, Brigitte M. [Institute of Experimental Gene Therapy and Cancer Research, Rostock University Medical Center, Rostock (Germany); Siatkowski, Marcin; Fuellen, Georg [Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Rostock (Germany); Vollmar, Brigitte [Institute for Experimental Surgery, Rostock University Medical Center, Rostock (Germany); Abshagen, Kerstin, E-mail: kerstin.abshagen@uni-rostock.de [Institute for Experimental Surgery, Rostock University Medical Center, Rostock (Germany)

    2014-11-01

    Hepatic stellate cells (HSC) are well known initiators of hepatic fibrosis. After liver cell damage, HSC transdifferentiate into proliferative myofibroblasts, representing the major source of extracellular matrix in the fibrotic organ. Recent studies also demonstrate a role of HSC as progenitor or stem cell like cells in liver regeneration. Lhx2 is described as stem cell maintaining factor in different organs and as an inhibitory transcription factor in HSC activation. Here we examined whether a continuous expression of Lhx2 in HSC could attenuate their activation and whether Lhx2 could serve as a potential target for antifibrotic gene therapy. Therefore, we evaluated an adenoviral mediated overexpression of Lhx2 in primary HSC and investigated mRNA expression patterns by qRT-PCR as well as the activation status by different in vitro assays. HSC revealed a marked increase in activation markers like smooth muscle actin alpha (αSMA) and collagen 1α independent from adenoviral transduction. Lhx2 overexpression resulted in attenuated cell viability as shown by a slightly hampered migratory and contractile phenotype of HSC. Expression of stem cell factors or signaling components was also unaffected by Lhx2. Summarizing these results, we found no antifibrotic or stem cell maintaining effect of Lhx2 overexpression in primary HSC. - Highlights: • We performed adenoviral overexpression of Lhx2 in primary hepatic stellate cells. • Hepatic stellate cells expressed stem cell markers during cultivation. • Cell migration and contractility was slightly hampered upon Lhx2 overexpression. • Lhx2 overexpression did not affect stem cell character of hepatic stellate cells.

  13. Nitric oxide mediates effects of acute, not chronic, naltrexone on LPS-induced hepatic encephalopathy in cirrhotic rats.

    Science.gov (United States)

    Ghiassy, Bentolhoda; Rahimi, Nastaran; Javadi-Paydar, Mehrak; Gharedaghi, Mohammad Hadi; Norouzi-Javidan, Abbas; Dehpour, Ahmad R

    2017-01-01

    Recent studies suggest endogenous opioids and nitric oxide (NO) are involved in the pathophysiology of hepatic encephalopathy (HE). In this study, the interaction between the opioid receptor antagonist and NO was investigated on lipopolysaccharide (LPS)-induced HE in cirrhotic rats. Male rats were divided in the sham- and bile duct ligation (BDL)-operated groups. Animals were treated with saline; naltrexone (10 mg/kg, i.p.); or L-NAME (3 mg/kg, i.p.), alone or in combination with naltrexone. To induce HE, LPS (1 mg/kg, i.p.) was injected 1 h after the final drug treatment. HE scoring, hepatic histology, and plasma NO metabolites levels and mortality rate were recorded. Deteriorated level of consciousness and mortality after LPS administration significantly ameliorated following both acute and chronic treatment with naltrexone in cirrhotic rats. However, acute and chronic administration of L-NAME did not change HE scores in cirrhotic rats. The effects of acute but not chronic treatment of naltrexone on HE parameters were reversed by L-NAME. Plasma NOx concentrations elevated in BDL rats, which were decreased after acute and chronic treatment by naltrexone or L-NAME, significantly. We suggest both acute and chronic treatment with naltrexone improved LPS-induced HE. But, only acute treatment with naltrexone may affect through NO pathway.

  14. Autochthonous sporadic acute hepatitis E caused by two distinct subgenotype 3b hepatitis E virus strains with only 90% nucleotide identity.

    Science.gov (United States)

    Yamaguchi, Yasuko; Takagi, Hitoshi; Suzuki, Yuhei; Maruhashi, Kyoko; Kosone, Takashi; Kakizaki, Satoru; Sato, Ken; Yamada, Masanobu; Nagashima, Shigeo; Takahashi, Masaharu; Okamoto, Hiroaki

    2017-04-01

    Hepatitis E, which is caused by hepatitis E virus (HEV), is a public health concern in Japan, where the zoonotic food-borne transmission of HEV from domestic pigs and wild boars plays an important role. A 44-year-old Japanese man with autochthonous sporadic acute hepatitis E was admitted with general fatigue and moderate liver dysfunction. In the present study, two distinct HEV strains were recovered from the patient, who had consumed the raw or undercooked pig liver and intestine two or three times per week for 3 months before the disease onset. The recovered HEV strains were segregated into two clusters within subgenotype 3b, the open reading frame (ORF)1 and ORF2 sequences of which each showed ~10% difference, indicating HEV mixed infection. Because most notified patients with clinical HEV infection in Japan are diagnosed based on the detection of IgA-class HEV antibodies and because serum samples from only a limited number of HEV-infected patients are subjected to HEV RNA detection and nucleotide sequencing, it is very likely that patients with HEV mixed infection remain largely overlooked. The identification of sources of autochthonous HEV infection remains an important goal. Continued efforts to trace the sources of acute or chronic autochthonous HEV infection are warranted.

  15. Factors affecting the accuracy of controlled attenuation parameter (CAP in assessing hepatic steatosis in patients with chronic liver disease.

    Directory of Open Access Journals (Sweden)

    Kyu Sik Jung

    Full Text Available BACKGROUND & AIMS: Controlled attenuation parameter (CAP can measure hepatic steatosis. However, factors affecting its accuracy have not been described yet. This study investigated predictors of discordance between liver biopsy (LB and CAP. METHODS: A total of 161 consecutive patients with chronic liver disease who underwent LB and CAP were enrolled prospectively. Histological steatosis was graded as S0 (66% of hepatocytes. Cutoff CAP values were calculated from our cohort (250, 301, and 325 dB/m for ≥ S1, ≥ S2, and S3. Discordance was defined as a discrepancy of at least two steatosis stages between LB and CAP. RESULTS: The median age (102 males and 59 females was 49 years. Repartition of histological steatosis was as follows; S0 26.1% (n = 42, S1 49.7% (n = 80, S2 20.5% (n = 33, and S3 3.7% (n = 6. In multivariate linear regression analysis, CAP value was independently associated with steatosis grade along with body mass index (BMI and interquartile range/median of CAP value (IQR/MCAP (all P<0.05. Discordance was identified in 13 (8.1% patients. In multivariate analysis, histological S3 (odd ratio [OR], 9.573; 95% confidence interval [CI], 1.207-75.931; P = 0.033 and CAP value (OR, 1.020; 95% CI, 1.006-1.034; P = 0.006 were significantly associated with discordance, when adjusting for BMI, IQR/MCAP, and necroinflammation, reflected by histological activity or ALT level. CONCLUSIONS: Patients with high grade steatosis or high CAP values have a higher risk of discordance between LB and CAP. Further studies are needed to improve the accuracy of CAP interpretation, especially in patients with higher CAP values.

  16. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008312 Impact of hepatitis B virus infection on the activity of hematopoietic stem cell.SHI Yanmei(石雁梅),et al.Dept Infect Dis,1st Clin Coll,Harbin Med Univ,Harbin 150001.Chin J Infect Dis 2008;26(4):197-201.Objective To study the impact of hepatitis B virus (HBV)infection on the activity of cord hematopoieticstem cells.Methods CD34+cells were isolated from healthy human cord blood by mini MACS.Cells were

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

    Directory of Open Access Journals (Sweden)

    Hikmet Coban

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  19. Renal, gastrointestinal, and hepatic late effects in survivors of childhood acute myeloid leukemia treated with chemotherapy only--a NOPHO-AML study

    DEFF Research Database (Denmark)

    Skou, Anne-Sofie; Glosli, Heidi; Jahnukainen, Kirsi;

    2014-01-01

    BACKGROUND: We investigated the spectrum, frequency, and risk factors for renal, gastrointestinal, and hepatic late adverse effects in survivors of childhood acute myeloid leukemia (AML) without relapse treated with chemotherapy alone according to three consecutive AML trials by the Nordic Society...... with chemotherapy only experienced few renal, gastrointestinal, and hepatic late effects....

  20. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008449 A cross-sectional survey of occult hepatitis B virus infection in HIV-infected patients. MA Jianxin(马建新), et al.Dept Infect Dis, Shanghai Public Health Clin Center, Shanghai 201508. Chin J Intern Med 2008;47(7):574-577. Objective To assess the prevalence of occult HBV infection in HIV-infected patients.

  1. A novel multiplex real-time PCR assay for the concurrent detection of hepatitis A, B and C viruses in patients with acute hepatitis.

    Science.gov (United States)

    Park, Yongjung; Kim, Beom Seok; Choi, Kyu Hun; Shin, Dong Ho; Lee, Mi Jung; Cho, Yonggeun; Kim, Hyon-Suk

    2012-01-01

    A novel multiplex real-time PCR assay for concurrent detection of hepatitis viruses was evaluated for its clinical performance in screening patients with acute hepatitis. A total of 648 serum samples were collected from patients with acute symptoms of hepatitis. Concurrent detection of nucleic acids of HAV, HBV and HCV was performed using the Magicplex™ HepaTrio Real-time Detection test. Serum nucleic acid levels of HBV and HCV were also quantified by the Cobas® AmpliPrep/Cobas® TaqMan® (CAP/CTM) HBV and HCV tests. Patients' medical records were also reviewed. Concordance rates between the results from the HepaTrio and the CAP/CTM tests for the detection of HBV and HCV were 94.9% (k = 0.88) and 99.2% (k = 0.98), respectively. The cycle threshold values with the HepaTrio test were also correlated well with the levels of HBV DNA (r = -0.9230) and HCV RNA (r = -0.8458). The sensitivity and specificity of the HepaTrio test were 93.8% and 98.2%, respectively, for detecting HBV infection, and 99.1% and 100.0%, respectively, for HCV infection. For the HepaTrio test, 21 (3.2%) cases were positive for both HBV and HCV. Among the positive cases, 6 (0.9%) were true coinfections. This test also detected 18 (2.8%) HAV positives. The HepaTrio test demonstrated good clinical performance and produced results that agreed well with those of the CAP/CTM assays, especially for the detection of HCV. This assay was also able to detect HAV RNA from anti-HAV IgM-positive individuals. Therefore, this new multiplex PCR assay could be useful for the concurrent detection of the three hepatitis viruses.

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

    Science.gov (United States)

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

    2014-08-01

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

  3. Virological efficacy of combination therapy with corticosteroid and nucleoside analogue for severe acute exacerbation of chronic hepatitis B.

    Science.gov (United States)

    Yasui, S; Fujiwara, K; Nakamura, M; Miyamura, T; Yonemitsu, Y; Mikata, R; Arai, M; Kanda, T; Imazeki, F; Oda, S; Yokosuka, O

    2015-02-01

    The short-term prognosis of patients with severe acute exacerbation of chronic hepatitis B (CHB) leading to acute liver failure is extremely poor. We have reported the efficacy of corticosteroid in combination with nucleoside analogue in the early stages, but virological efficacy has not been documented. Our aim was to elucidate the virological efficacy of this approach. Thirteen patients defined as severe acute exacerbation of CHB by our uniform criteria were prospectively examined for virological responses to treatment. Nucleoside analogue and sufficient dose of corticosteroids were introduced as soon as possible after the diagnosis of severe disease. Of the 13 patients, 7 (54%) survived, 5 (38%) died and 1 (8%) received liver transplantation. The decline of HBV DNA was significant between the first 2 weeks (P = 0.02) and 4 weeks (P analogue has sufficient virological effect against severe acute exacerbation of CHB, and a rapid decline of HBV DNA is conspicuous in survived patients.

  4. Aberrantly elevated microRNA-34a in obesity attenuates hepatic responses to FGF19 by targeting a membrane coreceptor β-Klotho.

    Science.gov (United States)

    Fu, Ting; Choi, Sung-E; Kim, Dong-Hyun; Seok, Sunmi; Suino-Powell, Kelly M; Xu, H Eric; Kemper, Jongsook Kim

    2012-10-02

    MicroRNA-34a (miR-34a) is the most highly elevated hepatic miR in obese mice and is also substantially elevated in patients who have steatosis, but its role in obesity and metabolic dysfunction remains unclear. After a meal, FGF19 is secreted from the ileum; binds to a hepatic membrane receptor complex, FGF19 receptor 4 and coreceptor β-Klotho (βKL); and mediates postprandial responses under physiological conditions, but hepatic responses to FGF19 signaling were shown to be impaired in patients with steatosis. Here, we show an unexpected functional link between aberrantly elevated miR-34a and impaired βKL/FGF19 signaling in obesity. In vitro studies show that miR-34a down-regulates βKL by binding to the 3' UTR of βKL mRNA. Adenoviral-mediated overexpression of miR-34a in mice decreased hepatic βKL levels, impaired FGF19-activated ERK and glycogen synthase kinase signaling, and altered expression of FGF19 metabolic target genes. Consistent with these results, βKL levels were decreased and hepatic responses to FGF19 were severely impaired in dietary obese mice that have elevated miR-34a. Remarkably, in vivo antisense inhibition of miR-34a in obese mice partially restored βKL levels and improved FGF19 target gene expression and metabolic outcomes, including decreased liver fat. Further, anti-miR-34a treatment in primary hepatocytes of obese mice restored FGF19-activated ERK and glycogen synthase kinase signaling in a βKL-dependent manner. These results indicate that aberrantly elevated miR-34a in obesity attenuates hepatic FGF19 signaling by directly targeting βKL. The miR-34a/βKL/FGF19 axis may present unique therapeutic targets for FGF19-related human diseases, including metabolic disorders and cancer.

  5. Hepatic abnormal perfusion visible by magnetic resonance imaging in acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

    AIM:to study the prevalence and patterns of hepatic abnormal perfusion(HAP)visible by magnetic resonance imaging(MRI)in acute pancreatitis(AP).METHODS:Enhanced abdominal MRI was performed on 51 patients with AP.these patients were divided into two groups according to the MRI results:those with signs of gallstones,cholecystitis,common bile duct(CBD)stones or dilatation of the CBD on MRI and those without.the prevalence,shape and distribution of HAP in the two groups were analyzed and compared.the severity of AP was graded using the MR severity index(MRSI).the correlation between the MRSI and HAP was then analyzed.RESULTS:Of the 51 patients with AP,32(63%)showed at least one sign of gallbladder and CBD abnormalities on the MR images,while 19(37%)showed no sign of gallbladder or CBD abnormalities.Nineteen patients(37%)had HAP visible in the enhanced images,including strip-,wedge-or patch-shaped HAP distributed in the hepatic tissue adjacent to the gallbladder and left and right liver lobes.there were no significant differences in the prevalence of HAP(χ2=0.305,P=0.581>0.05)or HAP distribution in the liver(χ2=2.181,P=0.536>0.05)between patients with and without gallbladder and CBD abnormalities.there were no significant differences in the MRSI score between patients with and without HAP(t=0.559,P=0.552>0.05).HAP was not correlated with the MRSI score.CONCLUSION:HAP is common in patients with AP and appears strip-,patch-or wedge-shaped on MRI.HAP on MRI cannot be used to indicate the severity of AP.

  6. Serological cross reactivity to CMV and EBV causes problems in the diagnosis of acute hepatitis E virus infection.

    Science.gov (United States)

    Hyams, Catherine; Mabayoje, Diana A; Copping, Ruth; Maranao, Desmond; Patel, Mauli; Labbett, Wendy; Haque, Tanzina; Webster, Daniel P

    2014-03-01

    Hepatitis E virus (HEV) infection is an important public health concern as a major cause of enterically-transmitted hepatitis worldwide. The detectable window of viraemia is narrow, and HEV IgM and IgG rise simultaneously in acute infection. Furthermore, previous investigators have shown HEV IgM false positive reactions occur against EBV, CMV and potentially hepatitis A. A retrospective analysis of HEV serology testing was performed at a London tertiary referral hospital over a 3-year period. A thousand four hundred and twenty three serum samples were tested for HEV serology, with 33 samples HEV IgM positive and 28 HEV IgM equivocal. One hundred and eleven samples were HEV IgG positive but IgM negative suggesting past infection. No patients with HEV IgM positivity had false positive reactions against hepatitis A. A high degree of EBV and CMV cross reactivity was noted, with 33.3% and 24.2% of HEV IgM positive samples also testing positive for EBV and CMV IgM, respectively. HEV RNA was detected in four HEV IgM positive samples, indicating true positivity, although three demonstrated cross reactivity against EBV. Only 13.3% of samples with positive HEV IgM were HEV PCR positive, highlighting a low positive predictive value of serology testing. Overall a high level of HEV, EBV and CMV IgM cross reactivity was demonstrated, indicating that serology is unreliable in the diagnosis of acute viral hepatitis. It is concluded that that the diagnosis of viral hepatitis should be based on clinical features, raised transaminases, serology, and confirmatory PCR testing.

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

    Directory of Open Access Journals (Sweden)

    Simone Santana Viana

    2012-01-01

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

  8. Carnosic acid attenuates acute ethanol-induced liver injury via a SIRT1/p66Shc-mediated mitochondrial pathway.

    Science.gov (United States)

    Tian, Xinyao; Hu, Yan; Li, Mingzhu; Xia, Kun; Yin, Jiye; Chen, Juan; Liu, Zhaoqian

    2016-04-01

    Ethanol-induced liver injury is associated with oxidative stress and hepatocyte apoptosis. We previously demonstrated that SIRT1/p66Shc pathway activation attenuates hepatocyte apoptosis in liver ischemia/reperfusion. The current study aimed to investigate whether carnosic acid (CA), a natural antioxidant, can inhibit acute ethanol-induced apoptosis of hepatocytes and to determine the effect of SIRT1/p66Shc on this process. Our results showed that CA pretreatment significantly reduced ethanol-induced histologic damage, serum aminotransferase activity, and oxidative stress in rats. Importantly, CA pretreatment increased SIRT1 expression following ethanol exposure. Furthermore, p66Shc expression was negatively correlated with SIRT1 expression. Consistent with the results demonstrating p66Shc inhibition, CA pretreatment inhibited the release of cytochrome C and apoptosis-inducing factor (AIF) from mitochondria. After exposing L02 cells to ethanol, the increased SIRT1 expression induced by CA was abrogated by pharmacologic SIRT1 inhibition or the use of siRNA against SIRT1. Additionally, SIRT1 inhibition significantly abrogated the suppression of p66Shc expression and mitochondrial translocation induced by CA. Accordingly, CA-induced decreases in the release of cytochrome C and AIF and in mitochondrial apoptosis were nearly abolished by SIRT1 knockdown. These data indicated that CA-activated SIRT1 is protective against ethanol treatment. In summary, CA attenuates acute ethanol-induced liver injury via a SIRT1/p66Shc-mediated mitochondrial pathway.

  9. Hepatitis

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008079 Relationship of HBV genotype and bcp and pc mutations with HBV DNA rebound after lamivudine therapy. SU Minghua(苏明华), et al. Dept Infect Dis Clin Hosp, Guangxi Med Univ, Nanning 530027. World Chin J Digestol 2007;15(33):3507-3513. Objective To investigate the relationship of HBV gene mutations with HBV DNA rebound after lamivudine therapy. Methods Twenty-seven hepatitis B patients with HBV DNA rebound after

  10. Serial measurement of Doppler hepatic hemodynamic parameters for the diagnosis of acute rejection after live donor liver transplantation.

    Science.gov (United States)

    Sugimoto, Hiroyuki; Kato, Koichi; Hirota, Masashi; Takeda, Shin; Kamei, Hideya; Nakamura, Taro; Kiuchi, Tetsuya; Nakao, Akimasa

    2009-09-01

    To elucidate the role of Doppler hepatic hemodynamic parameters as surrogate markers of acute rejection (AR) after live donor liver transplantation (LDLT), serial Doppler measurements were prospectively performed during the first 2 weeks after LDLT to compare the longitudinal hepatic hemodynamic changes between patients with histologically proven AR and patients without histologically proven AR. Forty-six patients that had undergone adult-to-adult LDLT using a right lobe graft were enrolled in this study. The portal venous maximum velocity (PVV; cm/second), portal venous flow volume, hepatic arterial peak systolic velocity, hepatic arterial pulsatility index, hepatic venous maximum velocity, hepatic venous pulsatility index, and splenic arterial pulsatility index were measured. Fourteen patients were diagnosed by biopsy to have clinically relevant AR. Markedly increased PVV was seen soon after surgery and gradually decreased in both patients with clinically relevant AR and patients without clinically relevant AR. This serial change of decreasing PVV was significantly greater in patients with clinically relevant AR (P patients with clinically relevant AR was significantly lower than that in patients without clinically relevant AR (PVV on postoperative day 6: 35.6 +/- 21.3 versus 58.3 +/- 27.1 cm/second, respectively, P = 0.0080). A PVV cutoff value of 20.2 cm/second demonstrated the best accuracy for predicting clinically relevant AR. The sensitivity and specificity for predicting clinically relevant AR were 92.9% and 87.1%, respectively. The area under the curve was 0.94. In conclusion, serial Doppler measurement of hepatic parameters in LDLT is useful for the diagnosis of clinically relevant AR. Clinically relevant AR should therefore be suspected when a marked unexpected decrease in the PVV is observed.

  11. Analysis of the Molecular Evolution of Hepatitis B Virus Genotypes in Symptomatic Acute Infections in Argentina

    Science.gov (United States)

    Rodrigo, María Belén; Mojsiejczuk, Laura Noelia; Torres, Carolina; Sevic, Ina; González López Ledesma, María Mora; Perez, Paula Soledad; Bouzas, María Belén; Galdame, Omar; Marciano, Sebastián; Fainboim, Hugo; Flichman, Diego Martín; Campos, Rodolfo Héctor

    2016-01-01

    Hepatitis B virus (HBV) is a globally distributed human pathogen that leads to both self-limited and chronic infections. At least eight genotypes (A-H) with distinct geographical allocations and phylodynamic behaviors have been described. They differ substantially in many virological and probably some clinical parameters. The aim of this study was to analyze full-length HBV genome sequences from individuals with symptomatic acute HBV infections using phylogenetic and coalescent methods. The phylogenetic analysis resulted in the following subgenotype distribution: F1b (52.7%), A2 (18.2%), F4 (18.2%) and A1, B2, D3 and F2a 1.8% each. These results contrast with those previously reported from chronic infections, where subgenotypes F1b, F4, A2 and genotype D were evenly distributed. This differential distribution might be related to recent internal migrations and/or intrinsic biological features of each viral genotype that could impact on the probability of transmission. The coalescence analysis showed that after a diversification process started in the 80s, the current sequences of subgenotype F1b were grouped in at least four highly supported lineages, whereas subgenotype F4 revealed a more limited diversification pattern with most lineages without offspring in the present. In addition, the genetic characterization of the studied sequences showed that only two of them presented mutations of clinical relevance at S codifyng region and none at the polymerase catalytic domains. Finally, since the acute infections could be an expression of the genotypes currently being transmitted to new hosts, the predominance of subgenotype F1b might have epidemiological, as well as, clinical relevance due to its potential adverse disease outcome among the chronic cases. PMID:27433800

  12. Analysis of the Molecular Evolution of Hepatitis B Virus Genotypes in Symptomatic Acute Infections in Argentina.

    Directory of Open Access Journals (Sweden)

    María Belén Rodrigo

    Full Text Available Hepatitis B virus (HBV is a globally distributed human pathogen that leads to both self-limited and chronic infections. At least eight genotypes (A-H with distinct geographical allocations and phylodynamic behaviors have been described. They differ substantially in many virological and probably some clinical parameters. The aim of this study was to analyze full-length HBV genome sequences from individuals with symptomatic acute HBV infections using phylogenetic and coalescent methods. The phylogenetic analysis resulted in the following subgenotype distribution: F1b (52.7%, A2 (18.2%, F4 (18.2% and A1, B2, D3 and F2a 1.8% each. These results contrast with those previously reported from chronic infections, where subgenotypes F1b, F4, A2 and genotype D were evenly distributed. This differential distribution might be related to recent internal migrations and/or intrinsic biological features of each viral genotype that could impact on the probability of transmission. The coalescence analysis showed that after a diversification process started in the 80s, the current sequences of subgenotype F1b were grouped in at least four highly supported lineages, whereas subgenotype F4 revealed a more limited diversification pattern with most lineages without offspring in the present. In addition, the genetic characterization of the studied sequences showed that only two of them presented mutations of clinical relevance at S codifyng region and none at the polymerase catalytic domains. Finally, since the acute infections could be an expression of the genotypes currently being transmitted to new hosts, the predominance of subgenotype F1b might have epidemiological, as well as, clinical relevance due to its potential adverse disease outcome among the chronic cases.

  13. Free fatty acid-induced hepatic insulin resistance is attenuated following lifestyle intervention in obese individuals with impaired glucose tolerance

    DEFF Research Database (Denmark)

    Haus, Jacob M; Solomon, Thomas; Marchetti, Christine M;

    2010-01-01

    The objective of the study was to examine the effects of an exercise/diet lifestyle intervention on free fatty acid (FFA)-induced hepatic insulin resistance in obese humans.......The objective of the study was to examine the effects of an exercise/diet lifestyle intervention on free fatty acid (FFA)-induced hepatic insulin resistance in obese humans....

  14. Clinical implications of sulcal enhancement on postcontrast fluid attenuated inversion recovery images in patients with acute stroke symptoms

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyuk Joon; Kim, Eun Hee; Lee, Kyung Mi; Kim, Jae Hyoung; Bae, Yun Jung; Choi, Byoung Se; Jung, Cheol Kyu [Dept. of Radiology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

    2015-08-15

    Hyperintense acute reperfusion marker (HARM) without diffusion abnormalities is occasionally found in patients with an acute stroke. This study was to determine the prevalence and clinical implications of HARM without diffusion abnormalities. There was a retrospective review of magnetic resonance images 578 patients with acute strokes and identified those who did not have acute infarction lesions, as mapped by diffusion-weighted imaging (DWI). These patients were classified into an imaging-negative stroke and HARM without diffusion abnormalities groups, based on the DWI findings and postcontrast fluid attenuated inversion recovery images. The National Institutes of Health Stroke Scale (NIHSS) scores at admission, 1 day, and 7 days after the event, as well as clinical data and risk factors, were compared between the imaging-negative stroke and HARM without diffusion abnormalities groups. Seventy-seven acute stroke patients without any DWI abnormalities were found. There were 63 patients with an imaging-negative stroke (accounting for 10.9% of 578) and 13 patients with HARM without diffusion abnormalities (accounting for 2.4% of 578). The NIHSS scores at admission were higher in HARM without diffusion abnormalities group than in the imaging-negative stroke group (median, 4.5 vs. 1.0; p < 0.001), but the scores at 7 days after the event were not significantly different between the two groups (median, 0 vs. 0; p = 1). The patients with HARM without diffusion abnormalities were significantly older, compared with patients with an imaging-negative stroke (mean, 73.1 years vs. 55.9 years; p < 0.001). Patients with HARM without diffusion abnormalities are older and have similarly favorable short-term neurological outcomes, compared with the patients with imaging-negative stroke.

  15. Association between plasma fibrinogen levels and mortality in acute-on-chronic hepatitis B liver failure.

    Science.gov (United States)

    Shao, Zhexin; Zhao, Ying; Feng, Limin; Feng, Guofang; Zhang, Juanwen; Zhang, Jie

    2015-01-01

    Acute-on-chronic liver failure (AoCLF) is the most common type of liver failure and is associated with high mortality. Fibrinogen is critical in maintaining primary and secondary hemostasis. Therefore, we prospectively analyzed the association between fibrinogen and outcomes in AoCLF patients. Plasma fibrinogen was measured in 169 AoCLF, 173 chronic hepatitis B (CHB), and 171 healthy patients using a coagulation method. The predictive ability of fibrinogen for 3-month mortality in AoCLF patients was assessed using receiver operating characteristic (ROC) curve and multivariable logistic regression analyses. Plasma fibrinogen was significantly lower in nonsurvivor AoCLF patients compared with survivor AoCLF, CHB, and control patients. The sensitivity, specificity, and area under the ROC curve of 1/fibrinogen predicting mortality in AoCLF patients were 66.7%, 72.5%, and 0.746 (95% confidence interval (CI): 0.672-0.820, P fibrinogen cutoff value was 0.90 g/L. On multivariate logistic regression analysis, low fibrinogen was an independent factor predicting mortality (odds ratio: 0.304; 95% CI: 0.094-0.983; P = 0.047). Nonsurvivor AoCLF patients had significantly decreased fibrinogen levels, suggesting that low plasma fibrinogen may be a useful predictor of poor prognosis in AoCLF patients.

  16. Acute hepatitis C virus infection in a nurse trainee following a needlestick injury

    Science.gov (United States)

    Scaggiante, Renzo; Chemello, Liliana; Rinaldi, Roberto; Bartolucci, Giovanni Battista; Trevisan, Andrea

    2013-01-01

    Hepatitis C virus (HCV) infection after biological accident (needlestick injury) is a rare event. This report describes the first case of acute HCV infection after a needlestick injury in a female nursing student at Padua University Hospital. The student nurse was injured on the second finger of the right hand when recapping a 23-gauge needle after taking a blood sample. The patient who was the source was a 72-year-old female with weakly positive anti-HCV test results. Three months after the injury, at the second step of follow-up, a relevant increase in transaminases with a low viral replication activity (350 IU/mL) was observed in the student, indicating HCV infection. The patient tested positive for the same genotype (1b) of HCV as the injured student. A rapid decline in transaminases, which was not accompanied by viral clearance, and persistently positive HCV-RNA was described 1 mo later. Six months after testing positive for HCV, the student was treated with pegylated interferon plus ribavirin for 24 wk. A rapid virological response was observed after 4 wk of treatment, and a sustained virological response (SVR) was evident 6 mo after therapy withdrawal, confirming that the patient was definitively cured. Despite the favourable IL28B gene (rs12979860) CC- polymorphism observed in the patient, which is usually predictive of a spontaneous clearance and SVR, spontaneous viral clearance did not take place; however, infection with this genotype was promising for a sustained virological response after therapy. PMID:23382640

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

    Science.gov (United States)

    Glazer, Evan S; Zhu, Cihui; Hamir, Amir N; Borne, Agatha; Thompson, Catherine Shea; Curley, Steven A

    2011-12-01

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

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

    Science.gov (United States)

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

    2015-03-01

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

  19. [Coping strategies used by the family of a patient with acute fulminant hepatitis].

    Science.gov (United States)

    Iriarte Cerdán, Laura; Ruiz de Galarreta, Leire Martínez; Olano Lizarraga, Maddi; García Vivar, Cristina

    2012-04-01

    In the holistic care to the patient, the family should be an important part because its members are also affected by the situation. Therefore, nursing work should be directed to both the individual and his environment, being of great help to identify family's needs in order to meet their specific needs accurately. Also in the process of recovery the family goes through several stages of coping, each of them have its own characteristics and nurses' interventions should be adapted to them. The aim of this paper is to evidence the importance of caring for the family, identifying the stages of coping, recognizing their needs and identifying relevant care. For this, a clinical case of a family with a relative hospitalised in an intensive care unit because of an acute fulminant hepatitis was developed. The instruments used to carry out the analysis of the case are: family's needs described by Leske et al., coping stages identified by Kubler-Ross, and ways of coping scale developed by Lazarus and Folkman. Nurses have a relevant role due to their close contact with people, this helps to become a factor which facilitates the interaction of patient and family within the hospital environment. A holistic approach of nursing care involves assessing the needs of families to develop strategies for effective interventions.

  20. Hepato-splenic lymphoma: a rare entity mimicking acute hepatitis: A case report

    Institute of Scientific and Technical Information of China (English)

    Federico Perfetto; Roberto Tarquini; Franceco Mancuso; Simonetta di Lollo; Silvia Tozzini; Giampiero Belesi; Giacomo Laffi

    2003-01-01

    We reported a case of non-Hodgkin's lymphoma where liver involvement was the predominant clinical manifestation. A 27-year old man presented wiht markedly elevated serum aspartate aminotrasferase, alanine aminotransferase and lactate dehydrogenase, reduced prothrombin activity, thrombocytopenic purpura and hepato-splenomegaly without adenopathy. Viral, toxic,autoimmune and metabolic liver diseases were excluded.Bone marrow biopsy showed an intracapillary infiltration of T-lymphocytes with no evidence of lipid storage disease.Because of a progressive spleen enlargement, splenectomy was performed. Histological examination showed lymphomatous intrasinuses invasion of the spleen.Immunohistochemical investigation revealed the T phenotype of the neoplastic cells: CD45+, CD45RO+,CD3+, CD4-, CD8-, TIA1-. About 50 % of the lymphoid cells expressed CD56 antigen. The diagnosis of hepatosplenic T cell lymphoma was done. The patient was treated with chemotherapy, which induced a complete remission. Eighteen months later, he had a first relapse with increased aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase,thrombocytopenic purpura and blast in the peripheral blood.In spite of autologous bone marrow transplantation, he died twenty months after the diagnosis. Even in the absence of a mass lesion or lymphoadenopathy, hepatosplenic Tcell lymphoma should be considered in the differential diagnosis of a patient whose clinical course is atypical for acute hepatic dysfunction.

  1. Obesity Is Associated with Neutrophil Dysfunction and Attenuation of Murine Acute Lung Injury

    OpenAIRE

    Kordonowy, Lauren L.; Burg, Elianne; Lenox, Christopher C.; Gauthier, Lauren M.; Petty, Joseph M.; Antkowiak, Maryellen; Palvinskaya, Tatsiana; Ubags, Niki; Rincón, Mercedes; Dixon, Anne E.; Vernooy, Juanita H. J.; Fessler, Michael B.; Poynter, Matthew E.; Suratt, Benjamin T.

    2012-01-01

    Although obesity is implicated in numerous health complications leading to increased mortality, the relationship between obesity and outcomes for critically ill patients appears paradoxical. Recent studies have reported better outcomes and lower levels of inflammatory cytokines in obese patients with acute lung injury (ALI)/acute respiratory distress syndrome, suggesting that obesity may ameliorate the effects of this disease. We investigated the effects of obesity in leptin-resistant db/db o...

  2. C1q/TNF-Related Protein 9 (CTRP9) attenuates hepatic steatosis via the autophagy-mediated inhibition of endoplasmic reticulum stress.

    Science.gov (United States)

    Jung, Tae Woo; Hong, Ho Cheol; Hwang, Hwan-Jin; Yoo, Hye Jin; Baik, Sei Hyun; Choi, Kyung Mook

    2015-12-05

    C1q/TNF-Related Protein (CTRP) 9, the closest paralog of adiponectin, has been reported to protect against diet-induced obesity and non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanism has not been fully elucidated. We explored the protective effect of CTRP9 against hepatic steatosis and apoptosis, and identified the mechanisms through autophagy and endoplasmic reticulum (ER) stress using in vitro and in vivo experiments. Treating HepG2 cells with human recombinant CTRP9 significantly ameliorated palmitate- or tunicamycin-induced dysregulation of lipid metabolism, caspase 3 activity and chromatin condensation, which lead to reduction of hepatic triglyceride (TG) accumulation. CTRP9 treatment induced autophagy markers including LC3 conversion, P62 degradation, Beclin1 and ATG7 through AMPK phosphorylation in human primary hepatocytes. Furthermore, CTRP9 decreased palmitate- or tunicamycin-induced ER stress markers, such as eIF2α, CHOP and IRE-1, in HepG2 cells. Compound C, an AMPK inhibitor, and 3 methyladenine (3 MA), an autophagy inhibitor, canceled the effects of CTRP9 on ER stress, apoptosis and hepatic steatosis. In the livers of HFD-fed mice, adenovirus-mediated CTRP9 overexpression significantly induced AMPK phosphorylation and autophagy, whereas suppressed ER stress markers. In addition, both SREBP1-mediated lipogenic gene expression and apoptosis were significantly attenuated, which result in improvement in hepatic steatosis by overexpression of CTRP9. These results demonstrate that CTRP9 alleviates hepatic steatosis through relief of ER stress via the AMPK-mediated induction of autophagy.

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

    Directory of Open Access Journals (Sweden)

    Kenji Ando

    2009-11-01

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

  4. "Dose-effect-response" Relationships of Paeoniae Radix Rubra on α-Naphthylisothiocyanate-induced Acute Cholestatic Hepatitis in Rats

    Institute of Scientific and Technical Information of China (English)

    WEI Si-si; ZHAO Yan-ling; JIANG Feng-juan; JIA Lei; ZHU Yun; WANG Jia-bo; SUN Zhi-yong; LI Rui-sheng; XIAO Xiao-he

    2011-01-01

    Objective To investigate the hepatoprotective effects of Paeoniae Radix Rubra (PRR) at different doses against α-naphthylisothiocyanate (α-NIT)-induced acute cholestatic hepatitis in rats.Methods Rats were ig administrated with vehicle or PRR [(1,9,18,36,54,72,and 81 g/(kg·d)] 3 d before and 2 d after α-NIT (60 mg/kg) ig administration.The general status of rats,histopathology of liver,serum alanine aminotransaminase,aspartate aminotransaminase,total bilirubin,direct bilirubin,and alkaline phosphatase levels,were observed at respective time points (24 and 48 h) after α-NIT administration.Using cluster analysis and correspondence analysis,the "dose-effect-response" relationships of PRR were evaluated.Results The results showed that compared with model group,the serum biochemistry index significantly decreased with the increasing of PRR dosage (P < 0.01),and the change and necrosis of hepatic cellula,and inflammatory cell infiltration were gradually alleviated.However,the improvement was not obviously found in the low-dose group [1 g/(kg·d)].The cluster analysis and correspondence analysis results showed that different doses of PRR could significantly ameliorate α-NIT-induced acute cholestatic hepatitis of rats in a dose-dependent manner.Conclusion The experiments show that administration doses of PRR in clinical use should be added properly in order to gain the expectant therapeutic effect,especially in the treatment of heavy acute cholestasis hepatitis.

  5. Salvianolic Acids Attenuate Rat Hippocampal Injury after Acute CO Poisoning by Improving Blood Flow Properties

    Directory of Open Access Journals (Sweden)

    Li Guan

    2015-01-01

    Full Text Available Carbon monoxide (CO poisoning causes the major injury and death due to poisoning worldwide. The most severe damage via CO poisoning is brain injury and mortality. Delayed encephalopathy after acute CO poisoning (DEACMP occurs in forty percent of the survivors of acute CO exposure. But the pathological cause for DEACMP is not well understood. And the corresponding therapy is not well developed. In order to investigate the effects of salvianolic acid (SA on brain injury caused by CO exposure from the view point of hemorheology, we employed a rat model and studied the dynamic of blood changes in the hemorheological and coagulative properties over acute CO exposure. Compared with the groups of CO and 20% mannitol + CO treatments, the severe hippocampal injury caused by acute CO exposure was prevented by SA treatment. These protective effects were associated with the retaining level of hematocrit (Hct, plasma viscosity, fibrinogen, whole blood viscosities and malondialdehyde (MDA levels in red blood cells (RBCs. These results indicated that SA treatment could significantly improve the deformation of erythrocytes and prevent the damage caused by CO poisoning. Meanwhile, hemorheological indexes are good indicators for monitoring the pathological dynamic after acute CO poisoning.

  6. Aguamiel concentrate from Agave salmiana and its extracted saponins attenuated obesity and hepatic steatosis and increased Akkermansia muciniphila in C57BL6 mice

    Science.gov (United States)

    Leal-Díaz, Ana María; Noriega, Lilia G.; Torre-Villalvazo, Ivan; Torres, Nimbe; Alemán-Escondrillas, Gabriela; López-Romero, Patricia; Sánchez-Tapia, Mónica; Aguilar-López, Miriam; Furuzawa-Carballeda, Janette; Velázquez-Villegas, Laura A.; Avila-Nava, Azalia; Ordáz, Guillermo; Gutiérrez-Uribe, Janet A.; Serna-Saldivar, Sergio O.; Tovar, Armando R.

    2016-01-01

    Obesity and its comorbidities are a severe public health problem worldwide. The use of bioactive compounds found in some foods has been demonstrated to ameliorate the metabolic abnormalities associated with obesity. The purpose of this study was to assess whether the bioactive compounds present in aguamiel concentrate (AC) from Agave salmiana could attenuate glucose intolerance and hepatic steatosis in mice fed a high fat (HF) diet. HPLC-ELSD analysis showed that AC contained several saponins. The consumption of an AC extract rich in saponins reduced weight gain and fat mass and lowered serum glucose, insulin and LDL-cholesterol levels in mice fed a HF diet. Additionally, mice fed the saponin extract exhibited a reduced HOMA index and hepatic lipid levels and increased expression of genes involved in fatty acid oxidation. Saponins increased white adipose tissue browning, AMPK phosphorylation, fatty acid oxidation, and mitochondrial activity in skeletal muscle and energy expenditure in mice fed the HF diet. These metabolic changes were accompanied by an increase in the abundance of Akkermansia muciniphila in the gut microbiota. Therefore, Agave salmiana saponins can be an alternative to attenuate the metabolic changes that accompany obesity. PMID:27678062

  7. Effects of Acute Normovolemic Hemodilution on Perioperative Coagulation and Fibrinolysis in Elderly Patients Undergoing Hepatic Carcinectomy

    Institute of Scientific and Technical Information of China (English)

    Jian-rong Guo; Jun Yu; Xiao-ju Jin; Jin-man Du; Wei Guo; Xiao-hong Yuan

    2010-01-01

    Objective To observe the effects of acute normovolemie hemodilution (ANH) on coagulation func-tion and fibrinolysis in elderly patients undergoing hepatic carcinectomy.Methods Thirty elderly patients (aged 60-70 years) with liver cancer (American Society of Anesthe-siologists physical status Ⅰ-Ⅱ) scheduled for hepatic carcinectomy from February 2007 to February 2008 were randomly divided into ANH group (n= 15) and control group (n= 15). After tracheal intubation, patients in ANH group and control group were infused with 6% hydroxyethyl starch (HES) (130/0.4), and basic liquid containing 6% HES and routine Ringer's solution, respectively. In all the studied patients, blood samples were drawn at five different time points: before anesthesia induction (T1), 30 minutes after ANH (T2), I hour after start of operation (T3), immediately after operation (T4), and 24 hours after operation (T5). Then co-agulation function, soluble fibrin monomer complex (SFMC), prothrombin fragment (F1+2), and platelet membrane glycoprotein (activated GPIIb/GPIIIa and P-selectin) were measured.Results The perioperative blood loss was not significantly different between the two groups (P> 0.05). The volume of allogeneic blood transfusion in ANH group was significantly smaller than that in control group (350.5±70.7 mL vs. 457.8±181.3 mL, P0.05). SFMC and F1 +2 increased in both groups, but without statistical significance. P-selectin expression on the platelet surface of ANH group was significantly low-ered at T2 and T3 compared with the level at T1 (P< 0.05). Compared with control group, P-selectin was sig-nificandy lower in ANH group at T2-T5 (all P<0.05).Conclusions In elderly patients undergoing resection of liver cancer, ANH may not hamper fibri-nolysis and coagulation function. It could therefore be safe to largely reduce allogeneic blood transfusion.

  8. Gypsophila elegans isoorientin attenuates CCl₄-induced hepatic fibrosis in rats via modulation of NF-κB and TGF-β1/Smad signaling pathways.

    Science.gov (United States)

    Lin, Xing; Chen, Yongxin; Lv, Shujuan; Tan, Shimei; Zhang, Shijun; Huang, Renbin; Zhuo, Lang; Liang, Shuang; Lu, Zhongpeng; Huang, Quanfang

    2015-09-01

    The hepatoprotective effect of Gypsophila elegans isoorientin (GEI) was evaluated using a hepatic fibrosis model induced by CCl4 in rats. The results revealed that GEI significantly prevented CCl4-induced liver injury and fibrosis, as evidenced by the attenuation of histopathological changes, the decrease in serum aminotransferase, and the inhibition of collagen accumulation. GEI strongly inhibited lipid peroxidation and recruited anti-oxidative defense system. Moreover, GEI alleviated pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6 via inhibiting nuclear factor-κB (NF-κB) activation. In addition, GEI down-regulated the phosphorylation of Smad2/3 and up-regulated the level of hepatic Smad7, thereby inhibiting TGFβ1/Smad signaling pathway. In conclusion, our findings indicate that GEI can inhibit CCl4-induced hepatic fibrosis, which may be ascribed to its radical scavenging action, antioxidant activity, and modulation of NF-κB and TGF-β1/Smad signaling pathways.

  9. Exogenous heat shock cognate protein 70 pretreatment attenuates cardiac and hepatic dysfunction with associated anti-inflammatory responses in experimental septic shock.

    Science.gov (United States)

    Hsu, Jong-Hau; Yang, Rei-Cheng; Lin, Shih-Jen; Liou, Shu-Fen; Dai, Zen-Kong; Yeh, Jwu-Lai; Wu, Jiunn-Ren

    2014-12-01

    It has been recently demonstrated that intracellular heat shock cognate protein 70 (HSC70) can be released into extracellular space with physiologic effects. However, its extracellular function in sepsis is not clear. In this study, we hypothesize that extracellular HSC70 can protect against lipopolysaccharide (LPS)-induced myocardial and hepatic dysfunction because of its anti-inflammatory actions. In Wistar rats, septic shock developed with hypotension, tachycardia, and myocardial and hepatic dysfunction at 4 h following LPS administration (10 mg/kg, i.v.). Pretreatment with recombinant bovine HSC70 (20 μg/kg, i.v.) attenuated LPS-induced hypotension and tachycardia by 21% and 23%, respectively (P shock cognate protein 70 also prevented LPS-induced hypoglycemia (217 vs. 59 mg/dL, P shock, extracellular HSC70 conveys pleiotropic protection on myocardial, hepatic, and systemic derangements, with associated inhibition of proinflammatory mediators including tumor necrosis factor α, nitric oxide, cyclooxygenase 2, and matrix metalloproteinase 9, through mitogen-activated protein kinase/nuclear factor κB signaling pathways. Therefore, extracellular HSC70 may have a promising role in the prophylactic treatment of sepsis.

  10. 国产甲型肝炎减毒活疫苗和灭活疫苗安全性评价%Evaluation on Safety of Domestic Hepatitis A Attenuated Live Vaccine and Hepatitis A Inactivated Vaccine

    Institute of Scientific and Technical Information of China (English)

    张晓曙; 安婧; 刘建锋; 付鸿; 高丽; 李慧

    2012-01-01

    Objective To evaluate safety of domestic hepatitis A attenuated live vaccine (HepA-L) and hepatitis A inactivated vaccine (HepA-I), and provide reference for emergency vaccination after hepatitis A outbreaks. Methods 493 children aged 6-9 years confirmed negative with antibody to hepatitis A virus (Anti-HAV) produced by Abbott. U.S were divided randomly into four groups. Group A were vaccinated with domestic HepA-L, group B were vaccinated with domestic HepA-I, group C were vaccinated with hepatitis B vaccine made by recombinant deoxyribonucleic acid technigues in sacchararomyces cerevisiae yeast ( HepB-SCY ) as negative control and group D were vaccinated HepA-I produced by GlaxoSmithKline Biologicals S.A. (GSK)as positive control. The adverse events following immunization (AEFIs) were observed after 30 minutes, 24, 48 and 72 hours after vaccination with double-blind method. Results The main AEFIs were fever, local pain and scleroma. There were no other severe AEFIs. The rate of AEFIs was 13.95% in Group A, 15.25% in group B, 16.80% in group C and 25.62% in group D. There were no statistical differences between different groups (x2=6.953, P=0.073). Conclusion Domestic HepA-L, domestic HepA-I and imported HepA-I are Safe.%目的 评价国产甲型病毒性肝炎(甲肝)减毒活疫苗(Hepatitis A Attenuated Live Vaccine,HepA-L)和灭活疫苗(Hepatitis A Inactivated Vaccine,HepA-I)的安全性,为开展甲肝爆发疫情应急接种提供参考.方法 用美国雅培(Abbott)公司生产的抗甲肝病毒抗体(Antibody to Hepatitis A Virus,Anti-HAV)试剂,筛查未感染HAV的6~9岁儿童.将入选对象随机分为4组,分别接种国产HepA-L和国产HepA-I,以国产的重组乙型肝炎疫苗(酿酒酵母)(Hepatitis B Vaccine Made by Recombinant Deoxyribonucleic Acid Technigues in Sacchararomyces Cerevisiae Yeast,HepB-SCY)为阴性对照,以GlaxoSmithKline Biologicals S.A.(GSK)生产的HepA-I为阳性对照,采取随机双盲方法,观察接种疫苗后30min

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

    Science.gov (United States)

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

    2008-08-01

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

  12. Moderate (2%, v/v) Ethanol Feeding Alters Hepatic Wound Healing after Acute Carbon Tetrachloride Exposure in Mice.

    Science.gov (United States)

    Deshpande, Krutika T; Liu, Shinlan; McCracken, Jennifer M; Jiang, Lu; Gaw, Ta Ehpaw; Kaydo, Lindsey N; Richard, Zachary C; O'Neil, Maura F; Pritchard, Michele T

    2016-01-06

    Wound healing consists of three overlapping phases: inflammation, proliferation, and matrix synthesis and remodeling. Prolonged alcohol abuse can cause liver fibrosis due to deregulated matrix remodeling. Previous studies demonstrated that moderate ethanol feeding enhances liver fibrogenic markers and frank fibrosis independent of differences in CCl₄-induced liver injury. Our objective was to determine whether or not other phases of the hepatic wound healing response were affected by moderate ethanol after CCl₄ exposure. Mice were fed moderate ethanol (2% v/v) for two days and then were exposed to CCl₄ and euthanized 24-96 h later. Liver injury was not different between pair- and ethanol-fed mice; however, removal of necrotic tissue was delayed after CCl₄-induced liver injury in ethanol-fed mice. Inflammation, measured by TNFα mRNA and protein and hepatic Ly6c transcript accumulation, was reduced and associated with enhanced hepatocyte apoptosis after ethanol feeding. Hepatocytes entered the cell cycle equivalently in pair- and ethanol-fed mice after CCl₄ exposure, but hepatocyte proliferation was prolonged in livers from ethanol-fed mice. CCl₄-induced hepatic stellate cell activation was increased and matrix remodeling was prolonged in ethanol-fed mice compared to controls. Taken together, moderate ethanol affected each phase of the wound healing response to CCl₄. These data highlight previously unknown effects of moderate ethanol exposure on hepatic wound healing after acute hepatotoxicant exposure.

  13. Moderate (2%, v/v Ethanol Feeding Alters Hepatic Wound Healing after Acute Carbon Tetrachloride Exposure in Mice

    Directory of Open Access Journals (Sweden)

    Krutika T. Deshpande

    2016-01-01

    Full Text Available Wound healing consists of three overlapping phases: inflammation, proliferation, and matrix synthesis and remodeling. Prolonged alcohol abuse can cause liver fibrosis due to deregulated matrix remodeling. Previous studies demonstrated that moderate ethanol feeding enhances liver fibrogenic markers and frank fibrosis independent of differences in CCl4-induced liver injury. Our objective was to determine whether or not other phases of the hepatic wound healing response were affected by moderate ethanol after CCl4 exposure. Mice were fed moderate ethanol (2% v/v for two days and then were exposed to CCl4 and euthanized 24–96 h later. Liver injury was not different between pair- and ethanol-fed mice; however, removal of necrotic tissue was delayed after CCl4-induced liver injury in ethanol-fed mice. Inflammation, measured by TNFα mRNA and protein and hepatic Ly6c transcript accumulation, was reduced and associated with enhanced hepatocyte apoptosis after ethanol feeding. Hepatocytes entered the cell cycle equivalently in pair- and ethanol-fed mice after CCl4 exposure, but hepatocyte proliferation was prolonged in livers from ethanol-fed mice. CCl4-induced hepatic stellate cell activation was increased and matrix remodeling was prolonged in ethanol-fed mice compared to controls. Taken together, moderate ethanol affected each phase of the wound healing response to CCl4. These data highlight previously unknown effects of moderate ethanol exposure on hepatic wound healing after acute hepatotoxicant exposure.

  14. Hydrosulfide attenuates acute myocardial ischemic injury through the glycogen synthase kinase-3β/β-catenin signaling pathway.

    Science.gov (United States)

    Ge, Ning; Liu, Chao; Li, Guofeng; Xie, Lijun; Zhang, Qinzeng; Li, Liping; Hao, Na; Zhang, Jianxin

    2016-05-01

    The endogenous signaling gasotransmitter, hydrosulfide (H2S), has been shown to exert cardioprotective effects against acute myocardial infarction (AMI) due to ischemic injury. However, the mechanisms responsible for these effects are not yet fully understood. In this study, we investigated whether sodium hydrogen sulfide (NaHS), an H2S donor, attenuates acute myocardial ischemic injury through glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling. For this purpose, we utilized an in vivo rat model of AMI by occluding the left anterior descending coronary artery. NaHS (0.39, 0.78 or 1.56 mg/kg, intraperitoneally), the GSK-3β inhibitor, SB216763 (0.6 mg/kg, intravenously), or 1% dimethylsulfoxide (2 ml/kg, intravenously) were administered to the rats. The results demonstrated that the administration of medium- and high-dose NaHS and SB216763 significantly improved rat cardiac function, as evidenced by an increase in the mean arterial pressure, left ventricular developed pressure, contraction and relaxation rates, as well as a decrease in left ventricular end-diastolic pressure. In addition, the administration of NaHS and SB216763 attenuated myocardial injury as reflected by a decrease in apoptotic cell death and in the serum lactate dehydrogenase concentrations, and prevented myocardial structural changes. The administration of NaHS and SB216763 increased the concentrations of phosphorylated (p-)GSK-3β, the p-GSK-3β/t-GSK-3β ratio and downstream protein β-catenin. Moreover, western blot and immunohistochemical analyses of apoptotic signaling pathway proteins further established the cardioprotective potential of NaHS, as reflected by the upregulation of Bcl-2 expression, the downregulation of Bax expression, and a decrease in the number of TUNEL-positive stained cells. These findings suggest that hydrosulfide exerts cardioprotective effects against AMI-induced apoptosis through the GSK-3β/β-catenin signaling pathway.

  15. Propofol pretreatment attenuates lipopolysaccharide-induced acute lung injury in rats by activating the phosphoinositide-3-kinase/Akt pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, L.L. [Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province (China); Hu, G.C. [Department of Pharmacology, College of Medicine, University of Illinois at Chicago, Chicago, IL (United States); Zhu, S.S. [Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province (China); Li, J.F. [Department of Anesthesiology, Tengzhou Central People' s Hospital, Liaocheng, Shandong Province (China); Liu, G.J. [Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province (China)

    2014-10-14

    The aim of this study was to investigate the effect of propofol pretreatment on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the role of the phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathway in this procedure. Survival was determined 48 h after LPS injection. At 1 h after LPS challenge, the lung wet- to dry-weight ratio was examined, and concentrations of protein, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF) were determined using the bicinchoninic acid method or ELISA. Lung injury was assayed via lung histological examination. PI3K and p-Akt expression levels in the lung tissue were determined by Western blotting. Propofol pretreatment prolonged survival, decreased the concentrations of protein, TNF-α, and IL-6 in BALF, attenuated ALI, and increased PI3K and p-Akt expression in the lung tissue of LPS-challenged rats, whereas treatment with wortmannin, a PI3K/Akt pathway specific inhibitor, blunted this effect. Our study indicates that propofol pretreatment attenuated LPS-induced ALI, partly by activation of the PI3K/Akt pathway.

  16. Berberine attenuates adverse left ventricular remodeling and cardiac dysfunction after acute myocardial infarction in rats: role of autophagy.

    Science.gov (United States)

    Zhang, Yao-Jun; Yang, Shao-Hua; Li, Ming-Hui; Iqbal, Javaid; Bourantas, Christos V; Mi, Qiong-Yu; Yu, Yi-Hui; Li, Jing-Jing; Zhao, Shu-Li; Tian, Nai-Liang; Chen, Shao-Liang

    2014-12-01

    The present study aimed to test the hypothesis that berberine, a plant-derived anti-oxidant, attenuates adverse left ventricular remodelling and improves cardiac function in a rat model of myocardial infarction (MI). Furthermore, the potential mechanisms that mediated the cardioprotective actions of berberine, in particular the effect on autophagy, were also investigated. Acute MI was induced by ligating the left anterior descending coronary artery of Sprague-Dawley rats. Cardiac function was assessed by transthoracic echocardiography. The protein activity/levels of autophagy related to signalling pathways (e.g. LC-3B, Beclin-1) were measured in myocardial tissue by immunohistochemical staining and western blot. Four weeks after MI, berberine significantly prevented cardiac dysfunction and adverse cardiac remodelling. MI rats treated with low dose berberine (10 mg/kg per day) showed higher left ventricular ejection fraction and fractional shortening than those treated with high-dose berberine (50 mg/kg per day). Both doses reduced interstitial fibrosis and post-MI adverse cardiac remodelling. The cardioprotective action of berberine was associated with increased LC-3B II and Beclin-1 expressions. Furthermore, cardioprotection with berberine was potentially related to p38 MAPK inhibition and phospho-Akt activation. The present in vivo study showed that berberine is effective in promoting autophagy, and subsequently attenuating left ventricular remodelling and cardiac dysfunction after MI. The potential underlying mechanism is augmentation of autophagy through inhibition of p38 MAPK and activation of phospho-Akt signalling pathways.

  17. Serum metabolomic profiling in acute alcoholic hepatitis identifies multiple dysregulated pathways.

    Directory of Open Access Journals (Sweden)

    Vikrant Rachakonda

    Full Text Available 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

  18. A simple melatonin treatment protocol attenuates the response to acute stress in the sole Solea senegalensis

    DEFF Research Database (Denmark)

    Gesto, Manuel; Álvarez-Otero, Rosa; Conde-Sieira, Marta

    2016-01-01

    Several compounds have been tested in fish in order to attenuate the effects of different stressors, most often following previous observations in mammals. The hormone melatonin (MEL) and the amino acid L-tryptophan have been tested for this purpose with different degree of success. In Senegalese...... sole (Solea senegalensis) we have previously observed that during prolonged exposure to relatively mild stressors, the presence of MEL in the water helped to reduce the stress response. Here, we aimed to investigate the potential anti-stress effects of a short melatonin exposure that could be easily...

  19. Hypoksisk hepatitis

    DEFF Research Database (Denmark)

    Amadid, Hanan; Schiødt, Frank Vinholt

    2014-01-01

    Hypoxic hepatitis (HH), also known as ischaemic hepatitis or shock liver, is an acute liver injury caused by hepatic hypoxia. Cardiac failure, respiratory failure and septic shock are the main underlying conditions. In each of these conditions, several haemodynamic mechanisms lead to hepatic...... hypoxia. A shock state is observed in only 50% of cases. Thus, shock liver and ischaemic hepatitis are misnomers. HH can be a diagnostic pitfall but the diagnosis can be established when three criteria are met. Prognosis is poor and prompt identification and treatment of the underlying conditions...

  20. Tyrosol Attenuates High Fat Diet-Induced Hepatic Oxidative Stress: Potential Involvement of Cystathionine β-Synthase and Cystathionine γ-Lyase.

    Science.gov (United States)

    Sarna, Lindsei K; Sid, Victoria; Wang, Pengqi; Siow, Yaw L; House, James D; O, Karmin

    2016-05-01

    The Mediterranean diet is known for its cardioprotective effects. Recently, its protective qualities have also been reported in patients with non-alcoholic fatty liver disease (NAFLD). Oxidative stress is one of the important factors responsible for the development and progression of NAFLD. Hydrogen sulfide (H2S), a multifaceted gasotransmitter, has emerged as a potential therapeutic target in NAFLD. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are major enzymes responsible for endogenous H2S synthesis. Since oxidative stress contributes to NAFLD pathogenesis, the objective of this study was to investigate the effect of tyrosol, a major compound in olive oil and white wine, on high fat diet-induced hepatic oxidative stress and the mechanisms involved. Mice (C57BL/6) were fed for 5 weeks with a control diet (10 % kcal fat), a high fat diet (60 % kcal fat, HFD) or a HFD supplemented with tyrosol. High fat diet feeding induced hepatic oxidative stress, as indicated by the significant increase in lipid peroxidation and NADPH oxidase activity. Tyrosol supplementation significantly increased hepatic CBS and CSE expression and H2S synthesis in high fat diet-fed mice. Such effects were associated with the attenuation of high fat diet-induced hepatic lipid peroxidation and the restoration of the redox equilibrium of the antioxidant glutathione. Tyrosol also inhibited palmitic acid-induced oxidative stress in hepatocytes (HepG2 cells). These results suggest that the antioxidant properties of tyrosol may be mediated through functional changes in CBS and CSE activity, which might contribute to the hepatoprotective effect of the Mediterranean diet.

  1. Oxymatrine attenuates CCl4-induced hepatic fibrosis via modulation of TLR4-dependent inflammatory and TGF-β1 signaling pathways.

    Science.gov (United States)

    Zhao, Hong-Wei; Zhang, Zhen-Fang; Chai, Xuan; Li, Guang-Quan; Cui, He-Rong; Wang, Hong-Bo; Meng, Ya-Kun; Liu, Hui-Min; Wang, Jia-Bo; Li, Rui-Sheng; Bai, Zhao-Fang; Xiao, Xiao-He

    2016-07-01

    Oxymatrine (OMT) is able to effectively protect against hepatic fibrosis because of its anti-inflammatory property, while the underlying mechanism remains incompletely understood. In this study, forty rats were randomly divided into five groups: control group, model group (carbon tetrachloride, CCl4) and three OMT treatment groups (30, 60, 120mg/kg). After CCl4 alone, the fibrosis score was 20.2±0.8, and the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hydroxyproline content, and collagen I expression was elevated, but OMT blunted these parameters. Treatment with OMT prevented CCl4-induced increases in expression of pro-inflammatory and pro-fibrotic cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α, meanwhile OMT promoted the expression of anti-inflammatory and anti-fibrotic factors such as interleukin (IL)-10 and bone morphogenetic protein and activin membrane-bound inhibitor (Bambi). Moreover, lipopolysaccharides (LPS) and high mobility group box-1 (HMGB1), which activates Toll-like receptor 4 (TLR4) and modulate hepatic fibrogenesis through hepatic stellate cells (HSCs) or Kupffer cells, were significantly decreased by OMT treatment. These results were further supported by in vitro data. First, OMT suppressed the expression of TLR4 and its downstream pro-inflammatory cytokines, lowered the level of HMGB1, TGF-β1 in macrophages. Then, OMT promoted Bambi expression and thereby inhibited activation of HSCs mediated by transforming growth factor (TGF)-β1. In conclusion, this study showed that OMT could effectively attenuate the CCl4-induced hepatic fibrosis, and this effect may be due to modulation of TLR4-dependent inflammatory and TGF-β1 signaling pathways.

  2. Korean Pine Nut Oil Attenuated Hepatic Triacylglycerol Accumulation in High-Fat Diet-Induced Obese Mice.

    Science.gov (United States)

    Park, Soyoung; Shin, Sunhye; Lim, Yeseo; Shin, Jae Hoon; Seong, Je Kyung; Han, Sung Nim

    2016-01-21

    Korean pine nut oil (PNO) has been reported to influence weight gain and lipid metabolism. We examined whether PNO replacement in a high-fat diet (HFD) can ameliorate HFD-induced hepatic steatosis. Five-week-old male C57BL mice were fed control diets containing 10% of the energy from fat from PNO or soybean oil (SBO) (PC, SC) or HFDs with 45% of the energy from fat, with 10% from PNO or SBO and 35% from lard (PHFD, SHFD), for 12 weeks. Body weight gain and amount of white adipose tissue were lower in PHFD (10% and 18% lower, respectively) compared with SHFD. Hepatic triacylglycerol (TG) level was significantly lower in PHFD than the SHFD (26% lower). PNO consumption upregulated hepatic ACADL mRNA levels. The hepatic PPARG mRNA level was lower in the PC than in the SC. Expression of the sirtuin (SIRT) 3 protein in white adipose tissue was down-regulated in the SHFD and restored in the PHFD to the level in the lean control mice. SIRT 3 was reported to be upregulated under conditions of caloric restriction (CR) and plays a role in regulating mitochondrial function. PNO consumption resulted in lower body fat and hepatic TG accumulation in HFD-induced obesity, which seemed to be associated with the CR-mimetic response.

  3. Korean Pine Nut Oil Attenuated Hepatic Triacylglycerol Accumulation in High-Fat Diet-Induced Obese Mice

    Directory of Open Access Journals (Sweden)

    Soyoung Park

    2016-01-01

    Full Text Available Korean pine nut oil (PNO has been reported to influence weight gain and lipid metabolism. We examined whether PNO replacement in a high-fat diet (HFD can ameliorate HFD-induced hepatic steatosis. Five-week-old male C57BL mice were fed control diets containing 10% of the energy from fat from PNO or soybean oil (SBO (PC, SC or HFDs with 45% of the energy from fat, with 10% from PNO or SBO and 35% from lard (PHFD, SHFD, for 12 weeks. Body weight gain and amount of white adipose tissue were lower in PHFD (10% and 18% lower, respectively compared with SHFD. Hepatic triacylglycerol (TG level was significantly lower in PHFD than the SHFD (26% lower. PNO consumption upregulated hepatic ACADL mRNA levels. The hepatic PPARG mRNA level was lower in the PC than in the SC. Expression of the sirtuin (SIRT 3 protein in white adipose tissue was down-regulated in the SHFD and restored in the PHFD to the level in the lean control mice. SIRT 3 was reported to be upregulated under conditions of caloric restriction (CR and plays a role in regulating mitochondrial function. PNO consumption resulted in lower body fat and hepatic TG accumulation in HFD-induced obesity, which seemed to be associated with the CR-mimetic response.

  4. White Pitaya (Hylocereus undatus) Juice Attenuates Insulin Resistance and Hepatic Steatosis in Diet-Induced Obese Mice.

    Science.gov (United States)

    Song, Haizhao; Zheng, Zihuan; Wu, Jianan; Lai, Jia; Chu, Qiang; Zheng, Xiaodong

    2016-01-01

    Insulin resistance and hepatic steatosis are the most common complications of obesity. Pitaya is an important source of phytochemicals such as polyphenols, flavonoid and vitamin C which are related to its antioxidant activity. The present study was conducted to evaluate the influence of white pitaya juice (WPJ) on obesity-related metabolic disorders (e.g. insulin resistance and hepatic steatosis) in high-fat diet-fed mice. Forty-eight male C57BL/6J mice were assigned into four groups and fed low-fat diet with free access to water or WPJ, or fed high-fat diet with free access to water or WPJ for 14 weeks. Our results showed that administration of WPJ improved high-fat diet-induced insulin resistance, hepatic steatosis and adipose hypertrophy, but it exerted no influence on body weight gain in mice. Hepatic gene expression analysis indicated that WPJ supplement not only changed the expression profile of genes involved in lipid and cholesterol metabolism (Srebp1, HMGCoR, Cpt1b, HL, Insig1 and Insig2) but also significantly increased the expression levels of FGF21-related genes (Klb, FGFR2, Egr1 and cFos). In conclusion, WPJ protected from diet-induced hepatic steatosis and insulin resistance, which was associated with the improved FGF21 resistance and lipid metabolism.

  5. White Pitaya (Hylocereus undatus Juice Attenuates Insulin Resistance and Hepatic Steatosis in Diet-Induced Obese Mice.

    Directory of Open Access Journals (Sweden)

    Haizhao Song

    Full Text Available Insulin resistance and hepatic steatosis are the most common complications of obesity. Pitaya is an important source of phytochemicals such as polyphenols, flavonoid and vitamin C which are related to its antioxidant activity. The present study was conducted to evaluate the influence of white pitaya juice (WPJ on obesity-related metabolic disorders (e.g. insulin resistance and hepatic steatosis in high-fat diet-fed mice. Forty-eight male C57BL/6J mice were assigned into four groups and fed low-fat diet with free access to water or WPJ, or fed high-fat diet with free access to water or WPJ for 14 weeks. Our results showed that administration of WPJ improved high-fat diet-induced insulin resistance, hepatic steatosis and adipose hypertrophy, but it exerted no influence on body weight gain in mice. Hepatic gene expression analysis indicated that WPJ supplement not only changed the expression profile of genes involved in lipid and cholesterol metabolism (Srebp1, HMGCoR, Cpt1b, HL, Insig1 and Insig2 but also significantly increased the expression levels of FGF21-related genes (Klb, FGFR2, Egr1 and cFos. In conclusion, WPJ protected from diet-induced hepatic steatosis and insulin resistance, which was associated with the improved FGF21 resistance and lipid metabolism.

  6. Problems with diagnosis by fluid-attenuated inversion recovery magnetic resonance imaging in patients with acute aneurysmal subarachnoid hemorrhage.

    Science.gov (United States)

    Shimoda, Masami; Hoshikawa, Kaori; Shiramizu, Hideki; Oda, Shinri; Matsumae, Mitsunori

    2010-01-01

    The diagnostic efficacy of fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging and computed tomography (CT) for acute subarachnoid hemorrhage (SAH) were compared and the problems with diagnosis were investigated in 81 patients with aneurysmal SAH within 24 hours after onset who underwent FLAIR imaging and CT on admission. The number of hematomas in the cisterns and ventricles were evaluated by clot scores. In addition, the frequency of undetected hematomas was calculated for the cisterns and ventricles. Clot scores were significantly higher for FLAIR imaging than for CT in the lateral sylvian, quadrigeminal, and convexity cisterns. On the other hand, clot scores were significantly higher for CT than for FLAIR imaging in the interhemispheric and medial sylvian cisterns. The overall frequency of undetected SAH was 2% for FLAIR imaging and 14% for CT. With the exception of the interhemispheric and medial sylvian cisterns, the frequency of undetected SAH was higher for CT than for FLAIR imaging. In this study, FLAIR imaging was more sensitive than CT for the detection of acute SAH within 24 hours after onset. However, the diagnostic efficacy of FLAIR imaging was reduced in comparatively tight cisterns.

  7. Aquaporin-4 deficiency attenuates acute lesions but aggravates delayed lesions and microgliosis after cryoinjury to mouse brain

    Institute of Scientific and Technical Information of China (English)

    Wen-Zhen Shi; Chun-Zhen Zhao; Bing Zhao; Xiao-Liang Zheng; San-Hua Fang; Yun-Bi Lu; Wei-Ping Zhang; Zhong Chen; Er-Qing Wei

    2012-01-01

    Objective To determine whether aquaporin-4 (AQP4) regulates acute lesions,delayed lesions,and the associated microglial activation after cryoinjury to the brain.Methods Brain cryoinjury was applied to AQP4 knockout (KO)and wild-type mice.At 24 h and on days 7 and 14 after cryoinjury,lesion volume,neuronal loss,and densities of microglia and astrocytes were determined,and their changes were compared between AQP4 KO and wild-type mice.Results Lesion volume and neuronal loss in AQP4 KO mice were milder at 24 h following cryoinjury,but worsened on days 7 and 14,compared to those in wild-type mice.Besides,microglial density increased more,and astrocyte proliferation and glial scar formation were attenuated on days 7 and 14 in AQP4 KO mice.Conclusion AQP4 deficiency ameliorates acute lesions,but worsens delayed lesions,perhaps due to the microgliosis in the late phase.

  8. The Acute Phase of Trypanosoma cruzi Infection Is Attenuated in 5-Lipoxygenase-Deficient Mice

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    Adriana M. C. Canavaci

    2014-01-01

    Full Text Available In the present work we examine the contribution of 5-lipoxygenase- (5-LO- derived lipid mediators to immune responses during the acute phase of Trypanosoma cruzi infection in 5-LO gene knockout (5-LO−/− mice and wild-type (WT mice. Compared with WT mice, the 5-LO−/− mice developed less parasitemia/tissue parasitism, less inflammatory cell infiltrates, and a lower mortality. This resistance of 5-LO−/− mice correlated with several differences in the immune response to infection, including reduced PGE2 synthesis; sustained capacity of splenocytes to produce high levels of interleukin (IL-12 early in the infection; enhanced splenocyte production of IL-1β, IL-6, and IFN-γ; rapid T-cell polarization to secrete high quantities of IFN-γ and low quantities of IL-10; and greater numbers of CD8+CD44highCD62Llow memory effector T cells at the end of the acute phase of infection. The high mortality in WT mice was associated with increased production of LTB4/LTC4, T cell bias to produce IFN-γ, high levels of serum nitrite, and marked protein extravasation into the peritoneal cavity, although survival was improved by treatment with a cys-LT receptor 1 antagonist. These data also provide evidence that 5-LO-derived mediators negatively affect host survival during the acute phase of T. cruzi infection.

  9. iPLA2β deficiency attenuates obesity and hepatic steatosis in ob/ob mice through hepatic fatty-acyl phospholipid remodeling.

    Science.gov (United States)

    Deng, Xiuling; Wang, Jiliang; Jiao, Li; Utaipan, Tanyarath; Tuma-Kellner, Sabine; Schmitz, Gerd; Liebisch, Gerhard; Stremmel, Wolfgang; Chamulitrat, Walee

    2016-05-01

    PLA2G6 or GVIA calcium-independent PLA2 (iPLA2β) is identified as one of the NAFLD modifier genes in humans, and thought to be a target for NAFLD therapy. iPLA2β is known to play a house-keeping role in phospholipid metabolism and remodeling. However, its role in NAFLD pathogenesis has not been supported by results obtained from high-fat feeding of iPLA2β-null (PKO) mice. Unlike livers of human NAFLD and genetically obese rodents, fatty liver induced by high-fat diet is not associated with depletion of hepatic phospholipids. We therefore tested whether iPLA2β could regulate obesity and hepatic steatosis in leptin-deficient mice by cross-breeding PKO with ob/ob mice to generate ob/ob-PKO mice. Here we observed an improvement in ob/ob-PKO mice with significant reduction in serum enzymes, lipids, glucose, insulin as well as improved glucose tolerance, and reduction in islet hyperplasia. The improvement in hepatic steatosis measured by liver triglycerides, fatty acids and cholesterol esters was associated with decreased expression of PPARγ and de novo lipogenesis genes, and the reversal of β-oxidation gene expression. Notably, ob/ob livers contained depleted levels of lysophospholipids and phospholipids, and iPLA2β deficiency in ob/ob-PKO livers lowers the former, but replenished the latter particularly phosphatidylethanolamine (PE) and phosphatidylcholine (PC) that contained arachidonic (AA) and docosahexaenoic (DHA) acids. Compared with WT livers, PKO livers also contained increased PE and PC containing AA and DHA. Thus, iPLA2β deficiency protected against obesity and ob/ob fatty liver which was associated with hepatic fatty-acyl phospholipid remodeling. Our results support the deleterious role of iPLA2β in severe obesity associated NAFLD.

  10. Immune-driven adaptation of hepatitis B virus genotype D involves preferential alteration in B-cell epitopes and replicative attenuation--an insight from human immunodeficiency virus/hepatitis B virus coinfection.

    Science.gov (United States)

    Mondal, R K; Khatun, M; Ghosh, S; Banerjee, P; Datta, S; Sarkar, S; Saha, B; Santra, A; Banerjee, S; Chowdhury, A; Datta, S

    2015-07-01

    An important driving force behind the sequence diversity of hepatitis B virus (HBV) is viral adaptation to host immune responses. To gain an insight into the impact of host immunity on genetic diversification and properties of HBV, we characterized HBV of genotype D from treatment-naive hepatitis B e antigen-positive (EP) and hepatitis B e antigen-negative (EN) patients with chronic hepatitis B (CHB), where HBV is under stronger immune pressure, with that of HBV derived from human immunodeficiency virus (HIV)/HBV-coinfected individuals, where HIV infection has significantly weakened the immune system. Full-length sequence analysis showed that HBV heterogeneity was most extensive in EN-CHB followed by EP-CHB and HIV/HBV coinfection. The relative magnitude of non-synonymous changes within B-cell epitopes was greater than that in T-cell epitopes of HBV open reading frames (ORFs) in both EP-CHB and EN-CHB. Nine amino acid substitutions were identified in B-cell epitopes and one in a T-cell epitope of HBV in EN-CHB, most of which resulted in altered hydrophobicities, as determined using the Kyte and Doolittle method, relative to wild-type residues found in HBV from the HIV-positive group. Additionally, 19 substitutions occurred at significantly higher frequencies in non-epitope regions of HBV ORF-P in EN-CHB than HIV/HBV-coinfected patients. In vitro replication assay demonstrated that the substitutions, particularly in reverse transcriptase and RNaseH domains of ORF-P, resulted in a decline in replication capacity of HBV. Hence, our results indicate that HBV adapts to increasing immune pressure through preferential mutations in B-cell epitopes and by replicative attenuation. The viral epitopes linked to immune response identified in this study bear important implications for future HBV vaccine studies.

  11. Protocatechuic aldehyde attenuates cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation

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    Li Gao

    2016-12-01

    Full Text Available Cisplatin is a classic chemotherapeutic agent widely used to treat different types of cancers including ovarian, head and neck, testicular and uterine cervical carcinomas. However, cisplatin induces acute kidney injury by directly triggering an excessive inflammatory response, oxidative stress and programmed cell death of renal tubular epithelial cells. All of which lead to higher mortality rates in patients. In this study we examined the protective effect of protocatechuic aldehyde (PA in vitro in cisplatin-treated tubular epithelial cells and in vivo in cisplatin nephropathy. PA is a monomer of Traditional Chinese Medicine isolated from the root of S. miltiorrhiza. Results show that PA prevented cisplatin-induced decline of renal function and histological damage, which was confirmed by attenuation of KIM1 in both mRNA and protein levels. Moreover, PA reduced renal inflammation by suppressing oxidative stress and programmed cell death in response to cisplatin, which was further evidenced by in vitro data. Of note, PA suppressed NAPDH oxidases, including Nox2 and Nox4, in a dosage-dependent manner. Moreover, silencing Nox4, but not Nox2, removed the inhibitory effect of PA on cisplatin-induced renal injury, indicating that Nox4 may play a pivotal role in mediating the protective effect of PA in cisplatin-induced acute kidney injury. Collectively, our data indicate that PA largely blocked cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation without compromising anti-tumor activity of cisplatin. These findings suggest that PA and its derivatives may serve as potential protective agents for cancer patients with cisplatin treatment.

  12. Attenuation of acute nitrogen mustard-induced lung injury, inflammation and fibrogenesis by a nitric oxide synthase inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Malaviya, Rama; Venosa, Alessandro [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Hall, LeRoy [Drug Safety Sciences, Johnson and Johnson, Raritan, NJ 08869 (United States); Gow, Andrew J. [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Sinko, Patrick J. [Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Jeffrey D. [Department of Environmental and Occupational Medicine, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854 (United States); Laskin, Debra L., E-mail: laskin@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States)

    2012-12-15

    Nitrogen mustard (NM) is a toxic vesicant known to cause damage to the respiratory tract. Injury is associated with increased expression of inducible nitric oxide synthase (iNOS). In these studies we analyzed the effects of transient inhibition of iNOS using aminoguanidine (AG) on NM-induced pulmonary toxicity. Rats were treated intratracheally with 0.125 mg/kg NM or control. Bronchoalveolar lavage fluid (BAL) and lung tissue were collected 1 d–28 d later and lung injury, oxidative stress and fibrosis assessed. NM exposure resulted in progressive histopathological changes in the lung including multifocal lesions, perivascular and peribronchial edema, inflammatory cell accumulation, alveolar fibrin deposition, bronchiolization of alveolar septal walls, and fibrosis. This was correlated with trichrome staining and expression of proliferating cell nuclear antigen (PCNA). Expression of heme oxygenase (HO)-1 and manganese superoxide dismutase (Mn-SOD) was also increased in the lung following NM exposure, along with levels of protein and inflammatory cells in BAL, consistent with oxidative stress and alveolar-epithelial injury. Both classically activated proinflammatory (iNOS{sup +} and cyclooxygenase-2{sup +}) and alternatively activated profibrotic (YM-1{sup +} and galectin-3{sup +}) macrophages appeared in the lung following NM administration; this was evident within 1 d, and persisted for 28 d. AG administration (50 mg/kg, 2 ×/day, 1 d–3 d) abrogated NM-induced injury, oxidative stress and inflammation at 1 d and 3 d post exposure, with no effects at 7 d or 28 d. These findings indicate that nitric oxide generated via iNOS contributes to acute NM-induced lung toxicity, however, transient inhibition of iNOS is not sufficient to protect against pulmonary fibrosis. -- Highlights: ► Nitrogen mustard (NM) induces acute lung injury and fibrosis. ► Pulmonary toxicity is associated with increased expression of iNOS. ► Transient inhibition of iNOS attenuates acute

  13. Epidemiological, immunological and virological aspects of acute and chronic hepatitis C virus infections

    NARCIS (Netherlands)

    Thomas, X.V.

    2015-01-01

    Hepatitis C virus (HCV) is a single-stranded positive-sense RNA virus classified as a member of the Hepacivirus genus in the family Flavirviridae, and was first described by Choo et al. in 1989 as the causative agent of non-A-non-B post-transfusion hepatitis. HCV is a major cause of blood-borne infe

  14. Acute hepatitis B in a healthcare worker: A case report of genuine vaccination failure

    NARCIS (Netherlands)

    Boot, H.J.; Van Der Waaij, L.A.; Schirm, J.; Kallenberg, Cees; van Steenbergen, J.; Wolters, B.

    2009-01-01

    Background: Individuals who reach the antibody threshold level of 10 IU/I against the surface protein of the hepatitis B virus (HBV) after completion of a series of hepatitis B vaccination are considered to be long-term protected against a clinically manifest HBV infection. Case report: Here we desc

  15. Acute hepatitis B in a healthcare worker : A case report of genuine vaccination failure

    NARCIS (Netherlands)

    Boot, Hein J.; van der Waaij, Laurens A.; Schirm, Jurien; Kallenberg, Cees G. M.; van Steenbergen, Jim; Wolters, Bert

    2009-01-01

    Background: Individuals who reach the antibody threshold level of 10 IU/I against the surface protein of the hepatitis B virus (HBV) after completion of a series of hepatitis B vaccination are considered to be long-term protected against a clinically manifest HBV infection. Case report: Here we desc

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

    Science.gov (United States)

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

    2014-10-01

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

  17. Liver regeneration signature in hepatitis B virus (HBV-associated acute liver failure identified by gene expression profiling.

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    Oriel Nissim

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

  18. CT and MR imaging findings of appendiceal and hepatic mucormycosis in a patient with acute T-lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seo Youn; Lee, Min Hee; Lee, Hae Kyung; Yi, Boem Ha; Chin, Su Sie; Park, Seong Kyu; Chung, Jun Chul [Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of)

    2015-11-15

    Fungal infections occur in severely immunocompromised patients having profound and prolonged neutropenia. Here, we report a case of a 41-year-old female who, at the conclusion of induction chemotherapy for acute T-lymphoblastic leukemia, developed angioinvasive mucormycosis involving the appendix and liver, which presented as abdominal pain. This case is the first to provide detailed computed tomography and magnetic resonance imaging findings of angioinvasive appendiceal and hepatic mucormycosis. The implications of these findings as well as the diagnosis and management of mucormycosis, is further discussed.

  19. Acute, fatal Sarcocystis calchasi-associated hepatitis in Roller pigeons (Columba livia f. dom.) at Philadelphia Zoo.

    Science.gov (United States)

    Trupkiewicz, J G; Calero-Bernal, R; Verma, S K; Mowery, J; Davison, S; Habecker, P; Georoff, T A; Ialeggio, D M; Dubey, J P

    2016-01-30

    Four Roller pigeons (Columba livia f. dom.) at the Philadelphia Zoo died suddenly. Necropsy examination revealed macroscopic hepatitis. Microscopically, the predominant lesions were in liver, characterized with necrosis and mixed cell inflammatory response. Sarcocystis calchasi-like schizonts and free merozoites were identified in liver. Transmission electron microscopy confirmed that schizonts were in hepatocytes. A few schizonts were in spleen. PCR using S. calchasi-specific primers confirmed the diagnosis. Neither lesions nor protozoa were found in brain and muscles. This is the first report of acute visceral S. calchasi-associated sarcocystosis in naturally infected avian hosts.

  20. cis-Urocanic acid attenuates acute dextran sodium sulphate-induced intestinal inflammation.

    Directory of Open Access Journals (Sweden)

    Eric Albert

    Full Text Available On exposure to sunlight, urocanic acid (UCA in the skin is converted from trans to the cis form and distributed systemically where it confers systemic immunosuppression. The aim of this study was to determine if administration of cis-UCA would be effective in attenuating colitis and the possible role of IL-10. Colitis was induced in 129/SvEv mice by administering 5% dextran sodium sulfate (DSS for 7 days in drinking water. During this period mice received daily subcutaneously injections of cis-UCA or vehicle. To examine a role for IL-10, 129/SvEv IL-10(-/- mice were injected for 24 days with cis-UCA or vehicle. Clinical disease was assessed by measurement of body weight, stool consistency, and presence of blood. At sacrifice, colonic tissue was collected for histology and measurement of myeloperoxidase and cytokines. Splenocytes were analyzed for CD4+CD25+FoxP3+ T-regulatory cells via flow cytometry. Murine bone-marrow derived antigen-presenting cells were treated with lipopolysaccharide (LPS ± UCA and cytokine secretion measured. Our results demonstrated that cis-UCA at a dose of 50 µg was effective in ameliorating DSS-induced colitis as evidenced by reduced weight loss and attenuated changes in colon weight/length. This protection was associated with reduced colonic expression of CXCL1, an increased expression of IL-17A and a significant preservation of splenic CD4+CD25+FoxP3+ T-regulatory cells. cis-UCA decreased LPS induced CXCL1, but not TNFα secretion, from antigen-presenting cells in vitro. UCA reduced colonic levels of IFNγ in IL-10(-/- mice but did not attenuate colitis. In conclusion, this study demonstrates that cis-urocanic acid is effective in reducing the severity of colitis in a chemically-induced mouse model, indicating that pathways induced by ultraviolet radiation to the skin can influence distal sites of inflammation. This provides further evidence for a possible role for sunlight exposure in modulating inflammatory

  1. The expression of T-cell receptor Vβ subfamily in hepatitis B virus-related acute-on-chronic liver failure patients and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    施文娟

    2014-01-01

    Objective To investigate the expression and clinical significance of T-cell receptor(TCR)Vβsubfamily in hepatitis B virus(HBV)-related acute-on-chronic liverfailure(HBV-ACLF)patients.Methods Twenty-eight patients with HBV-ACLF(HBV-ACLF group)and 32patients with chronic hepatitis B flare(CHB-F group),who were treated in The Second People’s Hospital from

  2. Ebselen pretreatment attenuates ischemia/reperfusion injury and prevents hyperglycemia by improving hepatic insulin signaling and β-cell survival in gerbils.

    Science.gov (United States)

    Park, S; Kang, S; Kim, D S; Shin, B K; Moon, N R; Daily, J W

    2014-08-01

    Transient carotid artery occlusion causes ischemia/reperfusion (I/R) injury resulting in neuron and pancreatic β-cell death with consequential post-stroke hyperglycemia, which can lead to diabetes and may accelerate the development of Alzheimer's disease. Antioxidants have been shown to protect against the I/R injury and destruction of neurons. However, it is unknown whether the protection against I/R injury extends to the pancreatic β-cells. Therefore, we investigated whether treatment with ebselen, a glutathione peroxidase mimic, prevents neuronal and β-cell death following I/R in gerbils susceptible to stroke. After 28 days post artery occlusion, there was widespread neuronal cell death in the CA1 of the hippocampus and elevated IL-1β and TNF-α levels. Pretreatment with ebselen prevented the death by 56% and attenuated neurological damage (abnormal eyelid drooping, hair bristling, muscle tone, flexor reflex, posture, and walking patterns). Ischemic gerbils also exhibited impaired glucose tolerance and insulin sensitivity which induced post-stroke hyperglycemia associated with decreased β-cell mass due to increased β-cell apoptosis. Ebselen prevented the increased β-cell apoptosis, possibly by decreasing IL-1β and TNF-α in islets. Ischemia also attenuated hepatic insulin signaling, and expression of GLUT2 and glucokinase, whereas ebselen prevented the attenuation and suppressed gluconeogenesis by decreasing PEPCK expression. In conclusion, antioxidant protection by ebselen attenuated I/R injury of neurons and pancreatic β-cells and prevented subsequent impairment of glucose regulation that could lead to diabetes and Alzheimer's disease.

  3. Dietary unsaponifiable fraction from extra virgin olive oil supplementation attenuates acute ulcerative colitis in mice.

    Science.gov (United States)

    Sánchez-Fidalgo, S; Cárdeno, A; Sánchez-Hidalgo, M; Aparicio-Soto, M; Villegas, I; Rosillo, M A; de la Lastra, C Alarcón

    2013-02-14

    Extra virgin olive oil (EVOO) has demonstrated immunomodulatory and antiinflammatory properties in murine experimental ulcerative colitis (UC). In addition to its high monounsaturated fatty acid content, evidences have accumulated on the favorable properties of minor, although highly bioactive, components present in the unsaponifiable fraction (UF). The present study was designed to evaluate the effects of dietary EVOO's UF supplementation on acute UC. C57BL/6 mice were fed from weaning with sunflower oil (SD), EVOO diet and UF-enriched SD at 5% oil (SD+UF). After 30 days, mice were exposed to 3% dextran sulfate sodium (DSS) for 5 days developing acute colitis. After 4 days of DSS removal, animals were sacrificed and colons were histological and biochemically processed. Disease activity index and microscopic damage score were significantly improved in EVOO and SD+UF dietary groups versus SD group. In addition, both dietary treatments significantly induced decreases in MCP-1 and TNF-α levels, iNOS and COX-2 overexpression and p38 MAPKs activation in colon mucosa. Moreover, an upregulation of IκB expression was also observed after feeding the animals with both diets. However, no statistically differences between data from mice fed with EVOO or UF+SD diets were observed. Dietary enrichment with EVOO's UF reduces the damage in acute colitis model, alleviating the oxidative events and returning proinflammatory proteins expression to basal levels probably through p38 MAPK and NFκB signalling pathways. EVOO's UF diet might provide a basis for developing a new strategy in dietary supplementation for the prevention of UC.

  4. Astaxanthin Pretreatment Attenuates Hepatic Ischemia Reperfusion-Induced Apoptosis and Autophagy via the ROS/MAPK Pathway in Mice

    Directory of Open Access Journals (Sweden)

    Jingjing Li

    2015-05-01

    Full Text Available Background: Hepatic ischemia reperfusion (IR is an important issue in complex liver resection and liver transplantation. The aim of the present study was to determine the protective effect of astaxanthin (ASX, an antioxidant, on hepatic IR injury via the reactive oxygen species/mitogen-activated protein kinase (ROS/MAPK pathway. Methods: Mice were randomized into a sham, IR, ASX or IR + ASX group. The mice received ASX at different doses (30 mg/kg or 60 mg/kg for 14 days. Serum and tissue samples at 2 h, 8 h and 24 h after abdominal surgery were collected to assess alanine aminotransferase (ALT, aspartate aminotransferase (AST, inflammation factors, ROS, and key proteins in the MAPK family. Results: ASX reduced the release of ROS and cytokines leading to inhibition of apoptosis and autophagy via down-regulation of the activated phosphorylation of related proteins in the MAPK family, such as P38 MAPK, JNK and ERK in this model of hepatic IR injury. Conclusion: Apoptosis and autophagy caused by hepatic IR injury were inhibited by ASX following a reduction in the release of ROS and inflammatory cytokines, and the relationship between the two may be associated with the inactivation of the MAPK family.

  5. Fulminant hepatic failure in children: Etiology, histopathology and MDCT findings

    Energy Technology Data Exchange (ETDEWEB)

    Cakir, Banu [Baskent University Faculty of Medicine Department of Radiology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: banutopcu@yahoo.com; Kirbas, Ismail [Baskent University Faculty of Medicine Department of Radiology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: drismailk@yahoo.com; Demirhan, Beyhan [Baskent University Faculty of Medicine Department of Pathology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: beyhand@baskent-ank.edu.tr; Tarhan, Nefise Cagla [Baskent University Faculty of Medicine Department of Radiology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: caglat@gmail.com; Bozkurt, Alper [Baskent University Faculty of Medicine Department of Radiology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: abozkurt78@hotmail.com; Ozcay, Figen [Baskent University Faculty of Medicine Department of Pediatric Gastroenterology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: fozcay@baskent.edu.tr; Coskun, Mehmet [Baskent University Faculty of Medicine Department of Radiology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: mcoskun@baskent-ank.edu.tr

    2009-11-15

    Introduction: The purpose of this study is to determine the etiologies, histopathology and MDCT findings of children with fulminant hepatic failure admitted to our institution. Materials and methods: Between June 2004 and November 2006, 15 children with fulminant hepatic failure who underwent MDCT were included retrospectively in this study. Twelve patients had liver biopsies. The patients were divided into three groups as hyperacute (Group I), acute (Group II) and subacute (Group III) depending on onset of hepatic encephalopathy. Results: Hepatitis A in 4 patients, non-A, non-E hepatitis in 4; mushroom poisoning in 3; fulminant Wilson's disease in 2; autoimmune hepatitis in 1; and both hepatitis B and toxic hepatitis (with leflunomide treatment) in 1 patient were detected. MDCT of all three groups revealed diffuse reduction in hepatic attenuation in 11 patients; ascites in 9; periportal edema in 6; edema of gallbladder wall in 6; splenomegaly in 6; heterogeneous hepatic parenchyma in 6; hepatomegaly in 3; irregular contours of liver in 2; multiple micronodules in 1 and necrotic areas and regeneration in liver parenchyma in 2 patients. Histopathologic evaluation of liver biopsies showed massive hepatic necrosis, inflammatory cell infiltration and ductular proliferation in 8 patients, periportal edema in 6, edema of gallbladder wall in 5, regenerating nodules and fibrous septa consistent with cirrhotic pattern in 2, and regenerating nodules and necrotic areas in 2 patients. Conclusion: The most common MDCT findings in fulminant hepatic failure were diffuse reduction in hepatic attenuation and ascites. Massive hepatic necrosis was the most common histopathologic finding.

  6. The pericarp extract of Prunus persica attenuates chemotherapy-induced acute nephrotoxicity and hepatotoxicity in mice.

    Science.gov (United States)

    Lee, Chang Ki; Park, Kwang-Kyun; Hwang, Jae-Kwan; Lee, Sang Kook; Chung, Won-Yoon

    2008-06-01

    The fruit of Prunus persica L. (peach) is one of the common fruits. Its seed is well known as a traditional medicine (Persicae Semen) in Japan, China, and other Asian countries. However, the biological activities of P. persica fruit except its seed are poorly understood. This study was aimed at evaluating the protective effect of the pericarp extract of P. persica (PPE) against cisplatin-induced acute toxicity in mice. PPE (500 mg/kg, p.o.) showed a significant protection against the acute nephrotoxicity and hepatotoxicity induced by a single administration of cisplatin (45 mg/kg, i.p.) over a 16-hour period in mice. Its protective effect was evaluated by serum and tissue biochemical parameters. The pretreatment with PPE for 7 days prevented the cisplatin-induced decrease in the kidney and liver weights as a percentage of the total body weight. PPE significantly inhibited both the cisplatin-induced elevation in serum blood urea nitrogen and creatinine levels caused by kidney damage and the cisplatin-induced increase in serum alanine aminotransferase and aspartate aminotransferase levels by the liver damage. In addition, the administration of PPE caused recovery of the cisplatin-mediated changes in levels of serum nitric oxide and tissue lipid peroxidation, and reduced glutathione content returned to control levels. These results suggest that PPE protects against cisplatin-induced nephrotoxicity and hepatotoxicity by reducing cisplatin-induced oxidative stress in mice.

  7. Ginseng Berry Extract Attenuates Dextran Sodium Sulfate-Induced Acute and Chronic Colitis.

    Science.gov (United States)

    Zhang, Wei; Xu, Li; Cho, Si-Young; Min, Kyung-Jin; Oda, Tatsuya; Zhang, LiJun; Yu, Qing; Jin, Jun-O

    2016-04-05

    This study investigates the in vivo functions of ginseng berry extract (GB) as a therapy for dextran sodium sulfate (DSS)-induced colitis. C57BL/6 mice were given drinking water containing DSS (3%) for eight days to induce acute colitis. At the same time, the mice received an oral dose of GB (50 mg/kg) once daily. The GB-treated mice were less susceptible to the development of acute colitis than were control mice treated with saline, as determined by weight loss, disease activity, and colon histology. The administration of GB to DSS-treated mice also reduced the numbers and inhibited the activation of colon-infiltrating T cells, neutrophils, intestinal CD103(-)CD11c⁺ dendritic cells (cDCs), and macrophages. In addition, GB treatment promoted the migration of CD103⁺CD11c⁺ cDCs and expansion of Foxp3⁺ regulatory T cells in the colons of DSS-treated mice. Similarly, in the DSS-induced chronic colitis model, GB treatment improved the macroscopic and histological appearance of the colon wall when compared to untreated control mice, as indicated by longer colon length and lower histological scores. This is the first report to show that oral administration of GB suppresses immune activation and protects against experimentally induced colitis.

  8. Microbiological diagnostics of viral hepatitis

    OpenAIRE

    HASDEMİR, Ufuk

    2016-01-01

    Viral hepatitis is an infection that primarily affects the liverbut may also have systemic clinical manifestations. The vastmajority of viral hepatitis are caused by one of five hepatotropicviruses: hepatitis A virus (HAV), hepatitis B virus (HBV),hepatitis C virus (HCV), hepatitis D (delta) virus (HDV), andhepatitis E virus (HEV) (Table I) [1]. HBV, HCV, and HDValso cause chronic hepatitis, whereas HAV does not. HEVcauses acute hepatitis in normal hosts but can cause protractedand chronic he...

  9. Identification of hepatic niche harboring human acute lymphoblastic leukemic cells via the SDF-1/CXCR4 axis.

    Directory of Open Access Journals (Sweden)

    Itaru Kato

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

  10. Hepatite aguda colestática pelo propiltiouracil: relato de caso Acute cholestatic hepatitis induced by propylthiouracil: case report

    Directory of Open Access Journals (Sweden)

    Mônica Beatriz PAROLIN

    2000-04-01

    Full Text Available Propiltiouracil é uma droga amplamente utilizada no tratamento do hipertiroidismo. A hepatotoxicidade é um dos efeitos colaterais mais raros e também mais graves associados a ela. Relata-se um caso de hepatite aguda colestática que acomete um jovem de 15 anos em uso de propiltiouracil para tratamento de hipertiroidismo. Causas virais, metabólicas e autoimunes foram excluídas e a biopsia hepática revelou achados histopatológicos sugestivos de hepatite colestática induzida por droga. Com a suspensão da droga, houve remissão dos sintomas e normalização progressiva das provas de função hepática. Raramente, os pacientes em uso de propiltiouracil podem desenvolver injúria hepática grave.Propylthiouracil is widely used to treat patients with hyperthyroidism. However, propylthiouracil-induced hepatitis is an uncommon entity. The case of a 15-year-old boy treated with propylthiouracil for hyperthyroidism who developed a cholestatic acute hepatitis is reported. Viral, metabolic and autoimmune liver diseases were excluded and liver biopsy showed a pattern suggestive of drug-induced cholestatic hepatitis. After discontinuating the drug, there was a progressive resolution of symptoms and normalization of liver biochemical tests. Despite its rarity, patients receiving propylthiouracil are exposed to develop severe hepatotoxicity.

  11. Yin-Chen-Hao Tang Attenuates Severe Acute Pancreatitis in Rat: An Experimental Verification of In silico Network Target Prediction

    Science.gov (United States)

    Xiang, Hong; Wang, Guijun; Qu, Jialin; Xia, Shilin; Tao, Xufeng; Qi, Bing; Zhang, Qingkai; Shang, Dong

    2016-01-01

    Yin-Chen-Hao Tang (YCHT) is a classical Chinese medicine compound that has a long history of clinical use in China for the treatment of inflammatory diseases. However, the efficacy and mechanisms of YCHT for the treatment of severe acute pancreatitis (SAP) are not known. The current study investigated the pharmacological properties of YCHT against SAP and its underlying mechanisms. A computational prediction of potential targets of YCHT was initially established based on a network pharmacology simulation. The model suggested that YCHT attenuated SAP progress by apoptosis inducement, anti-inflammation, anti-oxidation and blood lipid regulation. These effects were validated in SAP rats. YCHT administration produced the following results: (1) significantly inhibited the secretion of pancreatic enzymes and protected pancreatic tissue; (2) obviously increased the number of in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells and induced apoptosis; (3) markedly inhibited neutrophil infiltration to the impaired pancreas and reduced the inflammatory reaction; (4) notably enhanced the activities of antioxidant enzymes and decreased the nitric oxide synthase levels; (5) significantly reduced the levels of triglycerides, total cholesterol and low-density lipoprotein and increased high-density lipoprotein; and (6) significantly up-regulated peroxisome proliferator-activated receptor-γ (PPARγ) and down-regulated nuclear factor-kappa B (NF-κB). In summary, these results demonstrated that YCHT attenuated SAP progress by inducing apoptosis, repressing inflammation, alleviating oxidative stress and regulating lipid metabolism partially via regulation of the NF-κB/PPARγ signal pathway. PMID:27790147

  12. Sesamin Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Inhibition of TLR4 Signaling Pathways.

    Science.gov (United States)

    Qiang, Li; Yuan, Jiang; Shouyin, Jiang; Yulin, Li; Libing, Jiang; Jian-An, Wang

    2016-02-01

    Recent studies suggested that TLR4 signaling pathways played an important role in the development of LPS-induced acute lung injury (ALI). Sesamin, a sesame lignan exacted from sesame seeds, has been shown to exhibit significant anti-inflammatory activity. The purpose of this study was to investigate the anti-inflammatory effects of sesamin on LPS-induced ALI in mice. Mice ALI model was induced by intratracheal instillation of LPS. Sesamin was given 1 h after LPS challenge. Our results showed that sesamin inhibited LPS-induced lung pathological change, edema, and myeloperoxidase (MPO) activity. Sesamin suppressed LPS-induced inflammatory cytokines TNF-α, IL-6, and IL-1β production. Furthermore, sesamin inhibited LPS-induced TLR4 expression and NF-κB activation. In conclusion, the results of this study indicated that sesamin protected against LPS-induced ALI by inhibition of TLR4 signaling pathways.

  13. Immune Complex Mediated Glomerulonephritis with Acute Thrombotic Microangiopathy following Newly Detected Hepatitis B Virus Infection in a Kidney Transplant Recipient

    Science.gov (United States)

    Burton, Hannah; Douthwaite, Sam; Newsholme, William; Horsfield, Catherine

    2016-01-01

    Hepatitis B virus (HBV) presents a risk to patients and staff in renal units. To minimise viral transmission, there are international and UK guidelines recommending HBV immunisation for patients commencing renal replacement therapy (RRT) and HBV surveillance in kidney transplant recipients. We report the case of a 56-year-old male who was immunised against HBV before starting haemodialysis. He received a deceased donor kidney transplant three years later, at which time there was no evidence of HBV infection. After a further six years he developed an acute kidney injury; allograft biopsy revealed an acute thrombotic microangiopathy (TMA) with glomerulitis, peritubular capillaritis, and C4d staining. Due to a “full house” immunoprofile, tests including virological screening were undertaken, which revealed acute HBV infection. Entecavir treatment resulted in an improvement in viral load and kidney function. HBV genotyping demonstrated a vaccine escape mutant, suggesting “past resolved” infection that reactivated with immunosuppression, though posttransplant acquisition cannot be excluded. This is the first reported case of acute HBV infection associated with immune complex mediated glomerulonephritis and TMA. Furthermore, it highlights the importance of HBV surveillance in kidney transplant recipients, which although addressed by UK guidelines is not currently practiced in all UK units.

  14. Immune Complex Mediated Glomerulonephritis with Acute Thrombotic Microangiopathy following Newly Detected Hepatitis B Virus Infection in a Kidney Transplant Recipient

    Directory of Open Access Journals (Sweden)

    Tracey Salter

    2016-01-01

    Full Text Available Hepatitis B virus (HBV presents a risk to patients and staff in renal units. To minimise viral transmission, there are international and UK guidelines recommending HBV immunisation for patients commencing renal replacement therapy (RRT and HBV surveillance in kidney transplant recipients. We report the case of a 56-year-old male who was immunised against HBV before starting haemodialysis. He received a deceased donor kidney transplant three years later, at which time there was no evidence of HBV infection. After a further six years he developed an acute kidney injury; allograft biopsy revealed an acute thrombotic microangiopathy (TMA with glomerulitis, peritubular capillaritis, and C4d staining. Due to a “full house” immunoprofile, tests including virological screening were undertaken, which revealed acute HBV infection. Entecavir treatment resulted in an improvement in viral load and kidney function. HBV genotyping demonstrated a vaccine escape mutant, suggesting “past resolved” infection that reactivated with immunosuppression, though posttransplant acquisition cannot be excluded. This is the first reported case of acute HBV infection associated with immune complex mediated glomerulonephritis and TMA. Furthermore, it highlights the importance of HBV surveillance in kidney transplant recipients, which although addressed by UK guidelines is not currently practiced in all UK units.

  15. Human mesenchymal stem cells attenuate early damage in a ventilated pig model of acute lung injury

    Directory of Open Access Journals (Sweden)

    Yuben Moodley

    2016-07-01

    Full Text Available Acute lung injury/acute respiratory distress syndrome (ALI/ARDS is a major cause of global morbidity and mortality. Mesenchymal stem cells (MSC have shown promise in treating inflammatory lung conditions. We hypothesised that human MSC (hMSC can improve ALI/ARDS through their anti-inflammatory actions. We subjected pigs (n = 6 to intravenous oleic acid (OA injury, ventilation and hMSC infusion, while the controls (n = 5 had intravenous OA, ventilation and an infusion vehicle control. hMSC were infused 1 h after the administration of OA. The animals were monitored for additional 4 h. Nuclear translocation of nuclear factor-light chain enhancer of activated B cells (NF-κB, a transcription factor that mediates several inflammatory pathways was reduced in hMSC treated pigs compared to controls (p = 0.04. There was no significant difference in lung injury, assessed by histological scoring in hMSC treated pigs versus controls (p = 0.063. There was no difference in neutrophil counts between hMSC-treated pigs and controls. Within 4 h, there was no difference in the levels of IL-10 and IL-8 pre- and post-treatment with hMSC. In addition, there was no difference in hemodynamics, lung mechanics or arterial blood gases between hMSC treated animals and controls. Subsequent studies are required to determine if the observed decrease in inflammatory transcription factors will translate into improvement in inflammation and in physiological parameters over the long term.

  16. Acute antibody-directed myostatin inhibition attenuates disuse muscle atrophy and weakness in mice.

    Science.gov (United States)

    Murphy, Kate T; Cobani, Vera; Ryall, James G; Ibebunjo, Chikwendu; Lynch, Gordon S

    2011-04-01

    Counteracting the atrophy of skeletal muscle associated with disuse has significant implications for minimizing the wasting and weakness in plaster casting, joint immobilization, and other forms of limb unloading, with relevance to orthopedics, sports medicine, and plastic and reconstructive surgery. We tested the hypothesis that antibody-directed myostatin inhibition would attenuate the loss of muscle mass and functional capacity in mice during 14 or 21 days of unilateral hindlimb casting. Twelve-week-old C57BL/10 mice were subjected to unilateral hindlimb plaster casting or served as controls. Mice received subcutaneous injections of saline or a mouse chimera of anti-human myostatin antibody (PF-354, 10 mg/kg; n = 6-9) on days 0 and 7 and were tested for muscle function on day 14, or were treated on days 0, 7, and 14 and tested for muscle function on day 21. Hindlimb casting reduced muscle mass, fiber size, and function of isolated soleus and extensor digitorum longus (EDL) muscles (P casting, when wasting and weakness had plateaued (P casting with reductions in muscle size and strength being most apparent during the first 14 days of disuse. These findings highlight the therapeutic potential of antibody-directed myostatin inhibition for disuse atrophy especially within the first 2 wk of disuse.

  17. Activated protein C attenuates acute ischaemia reperfusion injury in skeletal muscle.

    LENUS (Irish Health Repository)

    Dillon, J P

    2012-02-03

    Activated protein C (APC) is an endogenous anti-coagulant with anti-inflammatory properties. The purpose of the present study was to evaluate the effects of activated protein C in the setting of skeletal muscle ischaemia reperfusion injury (IRI). IRI was induced in rats by applying rubber bands above the levels of the greater trochanters bilaterally for a period of 2h followed by 12h reperfusion. Treatment groups received either equal volumes of normal saline or activated protein C prior to tourniquet release. Following 12h reperfusion, muscle function was assessed electrophysiologically by electrical field stimulation. The animals were then sacrificed and skeletal muscle harvested for evaluation. Activated protein C significantly attenuated skeletal muscle reperfusion injury as shown by reduced myeloperoxidase content, wet to dry ratio and electrical properties of skeletal muscle. Further in vitro work was carried out on neutrophils isolated from healthy volunteers to determine the direct effect of APC on neutrophil function. The effects of APC on TNF-alpha stimulated neutrophils were examined by measuring CD18 expression as well as reactive oxygen species generation. The in vitro work demonstrated a reduction in CD18 expression and reactive oxygen species generation. We conclude that activated protein C may have a protective role in the setting of skeletal muscle ischaemia reperfusion injury and that this is in part mediated by a direct inhibitory effect on neutrophil activation.

  18. Molecular evolution of GB virus B hepatitis virus during acute resolving and persistent infections in experimentally infected tamarins

    DEFF Research Database (Denmark)

    Takikawa, Shingo; Engle, Ronald E; Faulk, Kristina N

    2010-01-01

    GB virus B (GBV-B) causes acute hepatitis in experimentally infected tamarins. We compared evolutionary features in acute resolving and persistent GBV-B infection. We detected no evidence of evolution in four animals with clearance during weeks 9-12, whereas three animals with clearance during...... weeks 13-26 had several substitutions in their polyprotein sequence. A single tamarin had long-term GBV-B viraemia; analysis of virus recovered at weeks 2, 5, 12, 20, 26, 52 and 104 demonstrated that mutations accumulated over time. Overall, the amino acid substitution rate was 3.5x10(-3) and 1.1x10......(-3) substitutions per site year(-1) during weeks 1-52 and 53-104, respectively. Thus, there was a significant decrease in evolution over time, as found for hepatitis C virus. The rate of non-synonymous substitution per non-synonymous site compared with that of synonymous substitution per synonymous site decreased...

  19. The Effect of Emodin-Assisted Early Enteral Nutrition on Severe Acute Pancreatitis and Secondary Hepatic Injury

    Directory of Open Access Journals (Sweden)

    Gang Wang

    2007-01-01

    Full Text Available Severe acute pancreatitis (SAP characterized by atrocious progression and numerous complications often leads to a high mortality rate due to hypermetabolism, systemic inflammatory response syndrome (SIRS, and multiple organs dysfunction syndrome (MODS. Studies have revealed that both early enteral nutrition (EEN and emodin are potent agents in the management of SAP. However, whether the combined strategy is rational and more effective than either one alone remains unknown. In this regard, Wistar rats were treated with emodin-assisted EEN (EAEEN through enteral nutrient tubes after induction of SAP by retrograde infusion of 5.0% sodium taurocholate into the common pancreatic duct. Serum levels of amylase, tumor necrosis factor-alpha (TNF-α, angiotensin II (AngII, maleic dialdehyde (MDA, glutamic pyruvic transaminase (ALT, glutamic oxaloacetic transaminase (AST and C-reactive protein (CRP, intestinal secretory IgA (SIgA, pancreatic and hepatic myeloperoxidase (MPO activity as well as plasma levels of D-lactate and endotoxin were measured. In addition, pathologic alterations of pancreas and liver were observed microscopically. We found that EAEEN could significantly ameliorate these parameters and prevent pancreas and liver from serious damage. In conclusion, Our results indicated that EAEEN could exert beneficial effects on experimental SAP and obviously abate the severity of secondary hepatic injury. The combined strategy was safe and more effective than either one alone in the acute stage of SAP. This study also provided an experimental base for the clinical treatment of SAP patients with EAEEN.

  20. Quercetin attenuates the activation of hepatic stellate cells and liver fibrosis in mice through modulation of HMGB1-TLR2/4-NF-κB signaling pathways.

    Science.gov (United States)

    Li, Xi; Jin, Qianwen; Yao, Qunyan; Xu, Beili; Li, Zheng; Tu, Chuantao

    2016-11-02

    This study aimed to investigate the effects of quercetin on liver fibrogenesis in mice and to elucidate the underlying molecular mechanisms. Mice were administered with carbon tetrachloride (CCl4) for eight weeks to induce liver fibrosis and concomitantly orally treated with quercetin (50mgkg(-1)day(-1)). Here, we demonstrated that quercetin dramatically ameliorated liver injury, inflammation, and hepatic fibrogenesis induced by CCl4. Quercetin also inhibited the activation of hepatic stellate cells (HSC) in vivo and in vitro, as evaluated by α-smooth muscle actin (α-SMA) expression, which is a specific marker of HSC activation. Moreover, reduced fibrosis was associated with decreased high-mobility group box 1 (HMGB1), toll like receptor (TLR) 2 and TLR4 genes, and protein expression. Quercetin also inhibited the cytoplasmic translocation of HMGB1 in hepatocytes of fibrotic livers. Further investigation demonstrated that quercetin treatment significantly attenuated CCl4-induced nuclear translocation of the nuclear factor-κB (NF-κB) p65 and inhibited degradation of IκBα (an inhibitor of NF-κB) expression in the liver compared with vehicle-treated fibrotic mice. Considered together, our data indicate that quercetin has hepatoprotective and anti-fibrotic effects in animal models of liver fibrosis, the mechanism of which may be involved in modulating the HMGB1-TLR2/4-NF-κB signaling pathways.

  1. The Impact of Transient Hepatic Attenuation Differences in the Diagnosis of Pseudoaneurysm and Arteriovenous Fistula on Follow-Up CT Scans after Blunt Liver Trauma

    Directory of Open Access Journals (Sweden)

    Andreas Hjelm Brandt

    2014-09-01

    Full Text Available A feared complication to liver trauma is delayed vascular complication, such as pseudoaneurysm and arteriovenous fistula (PS/AF seen as focal enhancement on contrast-enhanced computed tomography (CT in the arterial phase. A hyperdense area termed transient hepatic attenuation difference (THAD representing altered hepatic blood flow can be seen in the arterial phase near the liver lesion. The objective of this study was to describe THAD and PS/AF on follow-up CT after blunt liver trauma, and to evaluate if THAD influenced the evaluation of PS/AF. Three radiology residents retrospectively evaluated scans of 78 patients. The gold standard for PS/AF was an evaluation by an experienced senior radiologist, while THAD was a consensus between the residents. PS/AF was present in 14% and THAD in 54%. THAD was located in the periphery of the lesion with hazy borders and mean HU levels of 100, while PS/AF was located within the lesion with focal enhancement and mean HU levels of 170 (p < 0.05. In evaluation of PS/AF, the likelihood of agreement between the observers and the gold standard was 89% when THAD was present, and 98% when THAD was absent (p = 0.04. THAD is common and can hamper the evaluation of PS/AF.

  2. Attenuation of oxidative stress and hepatic damage by some fermented tropical legume condiment diets in streptozotocin-induced diabetes in rats

    Institute of Scientific and Technical Information of China (English)

    Adedayo O Ademiluyi; Ganiyu Oboh

    2012-01-01

    Objective:To investigate the modulatory effect of fermented legume condiments diet on oxidative stress in streptozotocin(STZ) induced diabetic rats.Methods:Adult maleWistar rats were randomly divided into six groups with six animals in each group.Diabetes was induced by intraperitoneal injection ofSTZ(35 mg/kg b.w.).After being confirmed diabetic, the rats were fed with fermentedBambara groundnut,Locust beanandSoybean diets for14 days.The plasma was obtained after14-day treatment and analyzed for hepatic damage marker enzymes(AST,ALT andALP) andin vivo antioxidant indices.Results:The diabetic untreated rats showed elevated (P<0.05) levels ofAST,ALT,ALP and malondialdehyde with reduced activities of glutathione-S-transferase, catalase as well as plasma reduced glutathione, vitaminC and total protein content.However, treatment of diabetic rats with fermented legume condiments diets for14 days significantly(P<0.05) reversed the above parameters towards normalcy, suggesting their modulation of oxidative stress, which may be due to their high phenolic content and antioxidant capacity.Conclusions:The attenuation of oxidative stress and protection of hepatic tissue damage by the legume condiment diets inSTZ induced diabetic rats compare favourably with that of metformin, a well known oral hypoglycemic drug.

  3. Diagnosis and Treatment of Acute Hepatitis C Among HIV Positive Men Having Sex with Men

    NARCIS (Netherlands)

    S.J. Hullegie (Sebastiaan)

    2016-01-01

    textabstractThe general aim of this thesis is to study different aspects of an acute HCV infection in HIV positive MSM. The primary aim is to study the effectivity and safety of boceprevir in addition to pegIFN and RBV for the treatment of acute HCV infections within the Dutch Acute HCV in HIV study

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

    OpenAIRE

    Blystad Hans; Kløvstad Hilde; Nilsen Øivind; Rimšelienė Gražina; Aavitsland Preben

    2011-01-01

    Abstract Background Norway is classified as a low prevalence country for hepatitis B virus infection. Vaccination is only recommended for risk groups (intravenous drug users (IDUs), Men who have Sex with Men (MSM), immigrants and contacts of known carriers). We describe the epidemiology of reported cases of hepatitis B in Norway, during the years 1992-2009 in order to assess the validity of current risk groups and recommend preventive measures. Methods We used case based data from the nationa...

  5. Endothelial cells are damaged by autophagic induction before hepatocytes in Con A-induced acute hepatitis.

    Science.gov (United States)

    Yang, Ming-Chen; Chang, Chih-Peng; Lei, Huan-Yao

    2010-08-01

    We have reported both T-cell-dependent and -independent hepatitis in immunocompetent and immunodeficiency mice, respectively, after intravenous injection of Con A in mice. The mode of hepatocyte cell death is different: autophagy for T-cell-independent hepatitis in contrast to apoptosis for T-cell-dependent one. In this study, we further demonstrate that liver blood vessels are the first target in both modes. The infused Con A bond to the hepatic vascular endothelial cells and cause its damage with autophagy. Before the elevation of the serum alanine aminotransferase at 6 h post-injection, the plasma leakage and hemorrhage occur at 1-3 h without inflammation. Con A induces autophagy of endothelial cells and hemorrhage that is enhanced by IFN-gamma. Using the endothelial cell line HMEC-1, a dose- and time-dependent cell death with autophagic LC3-II (microtubule-associated protein light chain 3) conversion was induced by Con A and was enhanced by IFN-gamma. In conclusion, Con A induced autophagy on hepatic endothelial cells; the damage of liver blood vessel occurs before the induction of T-cell-dependent hepatitis via apoptosis or T-cell-independent hepatitis via autophagy.

  6. Dark chocolate attenuates intracellular pro-inflammatory reactivity to acute psychosocial stress in men: A randomized controlled trial.

    Science.gov (United States)

    Kuebler, Ulrike; Arpagaus, Angela; Meister, Rebecca E; von Känel, Roland; Huber, Susanne; Ehlert, Ulrike; Wirtz, Petra H

    2016-10-01

    Flavanol-rich dark chocolate consumption relates to lower risk of cardiovascular mortality, but underlying mechanisms are elusive. We investigated the effect of acute dark chocolate consumption on inflammatory measures before and after stress. Healthy men, aged 20-50years, were randomly assigned to a single intake of either 50g of flavanol-rich dark chocolate (n=31) or 50g of optically identical flavanol-free placebo-chocolate (n=34). Two hours after chocolate intake, both groups underwent the 15-min Trier Social Stress Test. We measured DNA-binding-activity of the pro-inflammatory transcription factor NF-κB (NF-κB-BA) in peripheral blood mononuclear cells, as well as plasma and whole blood mRNA levels of the pro-inflammatory cytokines IL-1β and IL-6, and the anti-inflammatory cytokine IL-10, prior to chocolate intake as well as before and several times after stress. We also repeatedly measured the flavanol epicatechin and the stress hormones epinephrine and cortisol in plasma and saliva, respectively. Compared to the placebo-chocolate-group, the dark-chocolate-group revealed a marginal increase in IL-10 mRNA prior to stress (p=0.065), and a significantly blunted stress reactivity of NF-κB-BA, IL-1β mRNA, and IL-6 mRNA (p's⩽0.036) with higher epicatechin levels relating to lower pro-inflammatory stress reactivity (p's⩽0.033). Stress hormone changes to stress were controlled. None of the other measures showed a significant chocolate effect (p's⩾0.19). Our findings indicate that acute flavanol-rich dark chocolate exerts anti-inflammatory effects both by increasing mRNA expression of the anti-inflammatory cytokine IL-10 and by attenuating the intracellular pro-inflammatory stress response. This mechanism may add to beneficial effects of dark chocolate on cardiovascular health.

  7. Swertiamarin ameliorates oleic acid induced lipid accumulation and oxidative stress by attenuating gluconeogenesis and lipogenesis in hepatic steatosis.

    Science.gov (United States)

    Patel, Tushar P; Rawal, Komal; Soni, Sanket; Gupta, Sarita

    2016-10-01

    Swertiamarin, a bitter secoiridoid glycoside, is an antidiabetic drug with lipid lowering activity meliorates insulin resistance in Type 2 Diabetes condition. Therefore, the study was designed to explore the antioxidant and hypolipidemic activity of swertiamarin in ameliorating NAFLD caused due to hepatic lipid accumulation, inflammation and insulin resistance. Steatosis was induced in HepG2 cells by supplementing 1mM oleic acid (OA) for 24h which was marked by significant accumulation of lipid droplets. This was determined by Oil Red O (ORO) staining and triglyceride accumulation. Swertiamarin (25μg/ml) decreased triglyceride content by 2 folds and effectively reduced LDH release (50%) activity by protecting membrane integrity thus, preventing apoptosis evidenced by reduced cleavage of Caspase 3 and PARP1. We observed that swertiamarin significantly increased the expressions of major insulin signaling proteins like Insulin receptor (IR), PI(3)K, pAkt with concomitant reduction in p307 IRS-1. AMPK was activated by swertiamarin action, thus restoring insulin sensitivity in hepatocytes. In addition, qPCR results confirmed OA up-regulated Sterol Regulatory Element Binding Protein (SREBP)-1c and fatty acid synthase (FAS), resulting in increased fatty acid synthesis. Swertiamarin effectively modulated PPAR-α, a major potential regulator of carbohydrate metabolism which, in turn, decreased the levels of the gluconeogenic enzyme PEPCK, further restricting hepatic glucose production and fatty acid synthesis. Cumulatively, swertiamarin targets potential metabolic regulators AMPK and PPAR-α, through which it regulates hepatic glycemic burden, fat accumulation, insulin resistance and ROS in hepatic steatosis which emphasizes clinical significance of swertiamarin in regulating metabolism and as a suitable candidate for treating NAFLD.

  8. Pomegranate seed extract attenuates chemotherapy-induced acute nephrotoxicity and hepatotoxicity in rats.

    Science.gov (United States)

    Cayır, Kerim; Karadeniz, Ali; Simşek, Nejdet; Yıldırım, Serap; Karakuş, Emre; Kara, Adem; Akkoyun, Hürrem Turan; Sengül, Emin

    2011-10-01

    Cisplatin (CDDP), one of the most active cytotoxic agents against cancer, has adverse side effects, such as nephrotoxicity and hepatotoxicity. The present study was designed to investigate the potential protective effect of pomegranate seed extract (PSE) against oxidative stress caused by CDDP injury of the kidneys and liver by measuring tissue biochemical and antioxidant variables and immunohistochemically testing caspase-3-positive cells. Twenty-four Sprague-Dawley rats were divided into 4 groups: control; CDDP: injected intraperitoneally with CDDP (7 mg/kg body weight, single dose); PSE: treated for 15 consecutive days by gavage with PSE (300 mg/kg per day); and PSE+CDDP: treated by gavage with PSE 15 days after a single injection of CDDP. The degree of protection against CDDP injury afforded by PSE was evaluated by determining the levels of malondialdehyde as a measure of lipid peroxidation. The levels of glutathione and activities of glutathione peroxidase, glutathione S-transferase, and superoxide dismutase were estimated from liver and kidney homogenates; the liver and kidney were also histologically examined. PSE elicited a significant protective effect toward liver and kidney by decreasing the level of lipid peroxidation; elevating the levels of glutathione S-transferase; and increasing the activities of glutathione peroxidase, glutathione S-transferase, and superoxide dismutase. These biochemical observations were supported by immunohistochemical findings and suggested that PSE significantly attenuated nephrotoxicity and hepatotoxicity by the way of its antioxidant, radical-scavenging, and antiapoptotic effects. This PSE extract could be used as a dietary supplement in patients receiving chemotherapy medications.

  9. Dimethylfumarate attenuates restenosis after acute vascular injury by cell-specific and Nrf2-dependent mechanisms

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    Chang Joo Oh

    2014-01-01

    Full Text Available Excessive proliferation of vascular smooth muscle cells (VSMCs and incomplete re-endothelialization is a major clinical problem limiting the long-term efficacy of percutaneous coronary angioplasty. We tested if dimethylfumarate (DMF, an anti-psoriasis drug, could inhibit abnormal vascular remodeling via NF−E2-related factor 2 (Nrf2-NAD(PH quinone oxidoreductase 1 (NQO1 activity. DMF significantly attenuated neointimal hyperplasia induced by balloon injury in rat carotid arteries via suppression of the G1 to S phase transition resulting from induction of p21 protein in VSMCs. Initially, DMF increased p21 protein stability through an enhancement in Nrf2 activity without an increase in p21 mRNA. Later on, DMF stimulated p21 mRNA expression through a process dependent on p53 activity. However, heme oxygenase-1 (HO-1 or NQO1 activity, well-known target genes induced by Nrf2, were dispensable for the DMF induction of p21 protein and the effect on the VSMC proliferation. Likewise, DMF protected endothelial cells from TNF-α-induced apoptosis and the dysfunction characterized by decreased eNOS expression. With knock-down of Nrf2 or NQO1, DMF failed to prevent TNF-α-induced cell apoptosis and decreased eNOS expression. Also, CD31 expression, an endothelial specific marker, was restored in vivo by DMF. In conclusion, DMF prevented abnormal proliferation in VSMCs by G1 cell cycle arrest via p21 upregulation driven by Nrf2 and p53 activity, and had a beneficial effect on TNF-α-induced apoptosis and dysfunction in endothelial cells through Nrf2–NQO1 activity suggesting that DMF might be a therapeutic drug for patients with vascular disease.

  10. The ethanolic extract of Juglans sinensis leaves and twigs attenuates CCl4-induced hepatic oxidative stress in rats

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    Heejung Yang

    2015-01-01

    Full Text Available Background: The nuts of Juglans sinensis Dode, walnut tree, are rich in unsaturated fatty acids and bioactive compounds with antioxidant activity on liver damages. However, hepatoprotective activity of the leaves and twigs of J. sinensis have not intensively studied yet. Objective: Hepatoprotective activity of the refined ethanolic extract of J. sinensis (JSE3 was evaluated using carbon tetrachloride (CCl4 intoxicated rats. Materials and Methods: Hepatotoxicity was induced in Sprague Dawley rats by intraperitoneal injection of CCl4 for 6 weeks in the presence or absence of JSE3 (100 and 200 mg/kg body weight. The hepatoprotective activity of JSE3 was assessed by biochemical parameters including plasma aspartate aminotransferase (AST, alanine aminotransferase (ALT, and antioxidant enzymes, such as superoxide dismutase (SOD, glutathione reductase, glutathione peroxide, reduced glutathione and oxidized glutathione, along with histopathological studies on hepatic tissue. Results: JSE3 significantly decreased the elevated levels of AST and ALT and restored the reduced levels of antioxidant enzymes. JSE3 also decreased the amounts of collagen content accumulated by CCl4 intoxication. Conclusion: These results suggested that the refined extract of J. sinensis may have a potential to be developed as a therapeutic agent to treat hepatic diseases, such as fatty liver and hepatic fibrosis.

  11. Inhibition of p38 mitogen-activated protein kinase attenuates experimental autoimmune hepatitis: Involvement of nuclear factor kappa B

    Institute of Scientific and Technical Information of China (English)

    Xiong Ma; Yi-Tao Jia; De-Kai Qiu

    2007-01-01

    AIM: To investigate the role of p38 mitogen-activated protein kinase (p38MAPK) in murine experimental autoimmune hepatitis (EAH).METHODS: To induce EAH, the syngeneic S-100 antigen emulsified in complete Freud's adjuvant was injected intraperitoneally into adult male C57BI/6 mice. Liver injury was assessed by serum ALT and liver histology.The expression and activity of p38 MAPK were measured by Western blot and kinase activity assays. In addition,DNA binding activities of nuclear factor kappa B (NF-κB)were analyzed by electrophoretic mobility shift assay. The effects of SB203580, a specific p38 MAPK inhibitor, on liver injuries and expression of proinflammatory cytokines (interferon-γ, IL-12, IL-1β and TNF-α) were observed.RESULTS: The activity of p38 MAPK and NF-κB was increased and reached its peak 14 or 21 d after the first syngeneic S-100 administration. Inhibition of p38 MAPK activation by SB203580 decreased the activation of NF-κB and the expression of proinflammatory cytokines.Moreover, hepatic injuries were improved significantly after SB203580 administration.CONCLUSION: p38 MAPK and NF-κB play an important role in an animal model of autoimmune hepatitis (AIH)induced by autoantigens.

  12. Human Upcyte Hepatocytes: Characterization of the Hepatic Phenotype and Evaluation for Acute and Long-Term Hepatotoxicity Routine Testing.

    Science.gov (United States)

    Tolosa, Laia; Gómez-Lechón, M José; López, Silvia; Guzmán, Carla; Castell, José V; Donato, M Teresa; Jover, Ramiro

    2016-07-01

    The capacity of human hepatic cell-based models to predict hepatotoxicity depends on the functional performance of cells. The major limitations of human hepatocytes include the scarce availability and rapid loss of the hepatic phenotype. Hepatoma cells are readily available and easy to handle, but are metabolically poor compared with hepatocytes. Recently developed human upcyte hepatocytes offer the advantage of combining many features of primary hepatocytes with the unlimited availability of hepatoma cells. We analyzed the phenotype of upcyte hepatocytes comparatively with HepG2 cells and adult primary human hepatocytes to characterize their functional features as a differentiated hepatic cell model. The transcriptomic analysis of liver characteristic genes confirmed that the upcyte hepatocytes expression profile comes closer to human hepatocytes than HepG2 cells. CYP activities were measurable and showed a similar response to prototypical CYP inducers than primary human hepatocytes. Upcyte hepatocytes also retained conjugating activities and key hepatic functions, e.g. albumin, urea, lipid and glycogen synthesis, at levels close to hepatocytes. We also investigated the suitability of this cell model for preclinical hepatotoxicity risk assessments using multiparametric high-content screening, as well as transcriptomics and targeted metabolomic analysis. Compounds with well-documented in vivo hepatotoxicity were screened after acute and repeated doses up to 1 week. The evaluation of complex mechanisms of cell toxicity, drug-induced steatosis and oxidative stress biomarkers demonstrated that, by combining the phenotype of primary human hepatocytes and the ease of handling of HepG2 cells, upcyte hepatocytes offer suitable properties to be potentially used for toxicological assessments during drug development.

  13. Açai berry extract attenuates glycerol-induced acute renal failure in rats.

    Science.gov (United States)

    Unis, Amina

    2015-03-01

    Acute renal failure (ARF) is one of the most common problems encountered in hospitalized critically ill patients. In recent years great effort has been focused on the introduction of herbal medicine as a novel therapeutic agent for prevention of ARF. Hence, the current study was designed to investigate the effect of Açai berry extract (ABE) on glycerol-induced ARF in rats. Results of the present study showed that rat groups that received oral ABE in a dose of 100 and 200 mg/kg/day for 7 days before or 7 days after induction of ARF by a single intramuscular glycerol injection reported a significant improvement in kidney functions tests [decrease in serum urea, serum creatinine, and blood urea nitrogen (BUN)] when compared to the ARF model groups. Moreover, there was significant amelioration in renal oxidative stress markers [renal catalase (CAT), renal reduced glutathione (GSH)] and renal histopathological changes in the ABE-treated groups when compared to ARF model groups. The most significant improvement was reported in the groups where ABE was administered in a dose 200 mg/kg/day. These results indicate that ABE has a potential role in ameliorating renal damage involved in ARF.

  14. Combination of tadalafil and diltiazem attenuates renal ischemia reperfusion-induced acute renal failure in rats.

    Science.gov (United States)

    El-Sisi, Alaa E; Sokar, Samia S; Abu-Risha, Sally E; Ibrahim, Hanaa A

    2016-12-01

    Life threatening conditions characterized by renal ischemia/reperfusion (RIR) such as kidney transplantation, partial nephrectomy, renal artery angioplasty, cardiopulmonary bypass and aortic bypass surgery, continue to be among the most frequent causes of acute renal failure. The current study investigated the possible protective effects of tadalafil alone and in combination with diltiazem in experimentally-induced renal ischemia/reperfusion injury in rats. Possible underlying mechanisms were also investigated such as oxidative stress and inflammation. Rats were divided into sham-operated and I/R-operated groups. Anesthetized rats (urethane 1.3g/kg) were subjected to bilateral ischemia for 30min by occlusion of renal pedicles, then reperfused for 6h. Rats in the vehicle I/R group showed a significant (p˂0.05) increase in kidney malondialdehyde (MDA) content; myeloperoxidase (MPO) activity; TNF-α and IL-1β contents. In addition significant (p˂0.05) increase in intercellular adhesion molecule-1(ICAM-1) content, BUN and creatinine levels, along with significant decrease in kidney superoxide dismutase (SOD) activity. In addition, marked diffuse histopathological damage and severe cytoplasmic staining of caspase-3 were detected. Pretreatment with combination of tadalafil (5mg/kg bdwt) and diltiazem (5mg/kg bdwt) resulted in reversal of the increased biochemical parameters investigated. Also, histopathological examination revealed partial return to normal cellular architecture. In conclusion, pretreatment with tadalafil and diltiazem combination protected against RIR injury.

  15. SIRT1/3 Activation by Resveratrol Attenuates Acute Kidney Injury in a Septic Rat Model

    Science.gov (United States)

    Xu, Siqi; Wei, Siwei; Dai, Xingui

    2016-01-01

    Sepsis often results in damage to multiple organ systems, possibly due to severe mitochondrial dysfunction. Two members of the sirtuin family, SIRT1 and SIRT3, have been implicated in the reversal of mitochondrial damage. The aim of this study was to determine the role of SIRT1/3 in acute kidney injury (AKI) following sepsis in a septic rat model. After drug pretreatment and cecal ligation and puncture (CLP) model reproduction in the rats, we performed survival time evaluation and kidney tissue extraction and renal tubular epithelial cell (RTEC) isolation. We observed reduced SIRT1/3 activity, elevated acetylated SOD2 (ac-SOD2) levels and oxidative stress, and damaged mitochondria in RTECs following sepsis. Treatment with resveratrol (RSV), a chemical SIRT1 activator, effectively restored SIRT1/3 activity, reduced acetylated SOD2 levels, ameliorated oxidative stress and mitochondrial function of RTECs, and prolonged survival time. However, the beneficial effects of RSV were greatly abrogated by Ex527, a selective inhibitor of SIRT1. These results suggest a therapeutic role for SIRT1 in the reversal of AKI in septic rat, which may rely on SIRT3-mediated deacetylation of SOD2. SIRT1/3 activation could therefore be a promising therapeutic strategy to treat sepsis-associated AKI. PMID:28003866

  16. Inhibition of 5-Lipoxygenase Pathway Attenuates Acute Liver Failure by Inhibiting Macrophage Activation

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    Lu Li

    2014-01-01

    Full Text Available This study aimed to investigate the role of 5-lipoxygenase (5-LO in acute liver failure (ALF and changes in macrophage activation by blocking it. ALF was induced in rats by administration of D-galactosamine (D-GalN/lipopolysaccharide (LPS. Rats were injected intraperitoneally with AA-861 (a specific 5-LO inhibitor, 24 hr before D-GalN/LPS administration. After D-GalN/LPS injection, the liver tissue was collected for assessment of histology, macrophage microstructure, macrophage counts, 5-LO mRNA formation, protein expression, and concentration of leukotrienes. Serum was collected for detecting alanine aminotransferase (ALT, aspartate transaminase (AST, total bilirubin (Tbil, and tumor necrosis factor- (TNF-α. Twenty-four hours after injection, compared with controls, ALF rats were characterized by widespread hepatocyte necrosis and elevated ALT, AST, and Tbil, and 5-LO protein expression reached a peak. Liver leukotriene B4 was also significantly elevated. However, 5-LO mRNA reached a peak 8 hr after D-GalN/LPS injection. Simultaneously, the microstructure of macrophages was changed most significantly and macrophages counts were increased significantly. Moreover, serum TNF-α was also elevated. By contrast, AA-861 pretreatment significantly decreased liver necrosis as well as all of the parameters compared with the rats without pretreatment. Macrophages, via the 5-LO pathway, play a critical role in ALF, and 5-LO inhibitor significantly alleviates ALF, possibly related to macrophage inhibition.

  17. Hemin Attenuates Cisplatin-Induced Acute Renal Injury in Male Rats

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    Mohamed A. Al-Kahtani

    2014-01-01

    Full Text Available Background. The aim of this study is to investigate the protective effects of hemin (the heme oxygenase-1 [OH-1] inducer against nephrotoxic effects induced by cisplatin [cis-diamminedichloroplatinum II (CP] in male rats. Methods. The evaluation was performed through monitoring renal redox parameters: lipid peroxidation (LPO, glutathione peroxidase (GPx, superoxide dismutase (SOD, glutathione reductase (GR, and reduced glutathione (GSH. The work also examined renal function tests (urea and creatinine, tissue proinflammatory mediator like nitric oxide (NO, and kidney cytopathology. Results. A single intraperitoneal dose of CP (10 mg/kg b.w. caused significant elevation of blood urea, serum creatinine, and renal LPO and NO, along with significant decline of the activities of GPx and GR, but renal SOD activity and GSH level were statistically insignificant as compared to control group. Subcutaneous injection of hemin (40 µmol/kg b.w. partially ameliorated CP-induced renal damage, based on suppression of blood urea, serum creatinine, the renal MDA and NO levels, and increased antioxidant capacity in CP-treated rats. The results of histopathological and ultrastructural investigations supported the renoprotective effect of hemin against CP-induced acute toxicity. Conclusion. The induction of HO-1 by hemin is a promising approach in the treatment of CP-induced nephrotoxicity. However, further preclinical studies are warranted to test effectiveness of CP/hemin on the outcome of tumor chemotherapy.

  18. Calpain Inhibition Attenuates Apoptosis of Retinal Ganglion Cells in Acute Optic Neuritis

    Science.gov (United States)

    Smith, Amena W.; Das, Arabinda; Guyton, M. Kelly; Ray, Swapan K.; Rohrer, Baerbel

    2011-01-01

    Purpose. Optic neuritis (ON), inflammation of the optic nerve, is strongly associated with the pathogenesis of multiple sclerosis (MS) and is initiated by the attack of autoreactive T cells against self-myelin antigens, resulting in demyelination, degeneration of retinal ganglion cells (RGCs), and cumulative visual impairment. Methods. Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats on day 0, and animals received daily intraperitoneal injections of calpain inhibitor (calpeptin) or vehicle from day 1 until killed. Retinal cell death was analyzed by DNA fragmentation, and surviving ganglion cells were quantified after double labeling of retinal tissue with TUNEL and Brn3a. The expression of apoptotic and inflammatory proteins was determined by Western blotting. Results. It was demonstrated that calpain inhibition downregulates expression of proapoptotic proteins and the proinflammatory molecule nuclear factor-kappa B (NF-κB) in the retina of Lewis rats with acute EAE. Immunofluorescent labeling revealed that apoptotic cells in the RGC layer of vehicle-treated EAE animals were Brn3a positive, and a moderate dose of calpeptin dramatically reduced the frequency of apoptotic RGCs. Conclusions. These results suggest that calpain inhibition might be a useful supplement to immunomodulatory therapies such as corticosteroids in ON, due to its neuroprotective effect on RGCs. PMID:21613375

  19. Infusion of Bone Marrow Mesenchymal Stem Cells Attenuates Experimental Severe Acute Pancreatitis in Rats

    Science.gov (United States)

    Huang, Dandan; Gao, Jun; Gong, Yanfang; Wu, Hongyu; Xu, Aifang

    2016-01-01

    Background & Aims. Severe acute pancreatitis (SAP) remains a high-mortality disease. Bone marrow (BM) mesenchymal stem cells (MSCs) have been demonstrated to have plasticity of transdifferentiation and to have immunomodulatory functions. In the present study, we assessed the roles of MSCs in SAP and the therapeutic effects of MSC on SAP after transplantation. Methods. A pancreatitis rat model was induced by the injection of taurocholic acid (TCA) into the pancreatic duct. After isolation and characterization of MSC from BM, MSC transplantation was conducted 24 hrs after SAP induction by tail vein injection. The survival rate was observed and MSCs were traced after transplantation. The expression of TNF-α and IL-1β mRNA in the transplantation group was also analyzed. Results. The survival rate of the transplantation group was significantly higher compared to the control group (p pancreas and BM 3 days after transplantation. The expression of TNF-α and IL-1β mRNA in the transplantation group was significantly lower than in the control group in both the pancreas and the lungs (p < 0.05). Conclusions. MSC transplantation could improve the prognosis of SAP rats. Engrafted MSCs have the capacity of homing, migration, and planting during the treatment of SAP. PMID:27721836

  20. Leptin attenuates lipopolysaccharide or oleic acid-induced acute lung injury in mice.

    Science.gov (United States)

    Dong, Hai-Ying; Xu, Min; Ji, Zhen-Yu; Wang, Yan-Xia; Dong, Ming-Qing; Liu, Man-Ling; Xu, Dun-Quan; Zhao, Peng-Tao; Liu, Yi; Luo, Ying; Niu, Wen; Zhang, Bo; Ye, Jing; Li, Zhi-Chao

    2013-12-01

    Leptin is reported to be involved in acute lung injury (ALI). However, the role and underlying mechanisms of leptin in ALI remain unclear. The aim of this study was to determine whether leptin deficiency promoted the development of ALI. LPS or oleic acid (OA) were administered to wild-type and leptin deficient (ob/ob) mice to induce ALI. Leptin level, survival rate, and lung injury were examined. Results showed that leptin levels were predominantly increased in the lung, but also in the heart, liver, kidney, and adipose tissue after LPS adminiatration. Compared with wild-type mice, LPS- or OA-induced lung injury was worse and the survival rate was lower in ob/ob mice. Moreover, leptin deficiency promoted the release of proinflammatory cytokines. Exogenous administration of leptin reduced lethality in ob/ob mice and ameliorated lung injury partly through inhibiting the activation of NF-κB, p38, and ERK pathways. These results indicated that leptin deficiency contributed to the development of lung injury by enhancing inflammatory response, and a high level of leptin improved survival and protected against ALI.

  1. Intravenous injection of Xuebijing attenuates acute kidney injury in rats with paraquat intoxication

    Science.gov (United States)

    Xu, Jia-jun; Zhen, Jian-tao; Tang, Li; Lin, Qing-ming

    2017-01-01

    BACKGROUND: The study aimed to investigate the therapeutic benefits of intravenous Xuebijing on acute kidney injury (AKI) in rats with paraquat intoxication. METHODS: Male Sprague-Dawley rats were randomly divided equally into three groups: sham group (n=8), paraquat group (n=8) and Xuebijing-treated group (n=8) using a random number table. The rats were intraperitoneally injected with 50 mg/kg of paraquat. One hour after paraquat administration, the rats were treated intravenously with Xuebijing (8 mL/kg). At 12 hours after paraquat administration, serum was collected to evaluate kidney function, then the rats were sacrificed and kidney samples were immediately harvested. AKI scores were evaluated by renal histopathology and pro-inflammatory cytokines mRNA levels in kidney were assayed using real-time RT-PCR. RESULTS: Serum urea nitrogen, creatinine and AKI scores were significantly higher in the paraquat group, compared with the sham group (Pparaquat group (Pparaquat group (Pparaquat poisoning by suppressing inflammatory response. PMID:28123623

  2. l-Arginine supplementation protects against hepatic ischemia-reperfusion lesions in rabbits.

    Science.gov (United States)

    Taha, M O; Simões, M J; Haddad, M A; Capelato, R C; Budny, N; Matsumoto, A H; Soares, P C M; Santos, W M; Armeato, G D; Araki, C M; Gomes, J S M; Magalhães, K G; Tersariol, I L S; Monteiro, H P; Oliveira-Júnior, I S; Oliveira, I; Jurkiewicz, A; Caricati-Neto, A

    2009-04-01

    We evaluated the effects of a substrate in the biosynthesis of nitric oxide (NO)-l-arginine (LARG)-on hepatic lesions caused by ischemia/reperfusion (I/R) injury in rabbit livers. Rabbits were pretreated with LARG (150 mg/kg IV) or saline solution 0.9% (SS) before the hepatic I/R procedure. The effects of LARG on hepatic injury were evaluated before and after I/R. The warm hepatic I/R procedure produced profound acute liver injury, as indicated by elevated values of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactic dehydrogenase (LDH), as well as a high apoptotic cell count. All changes were attenuated by treatment with LARG before the hepatic I/R procedure. These results suggested that LARG produced protective effects on hepatic I/R lesions. This protective effect of LARG was probably associated with blocking generation of superoxide anions during the hepatic I/R procedure.

  3. Ischemic post-conditioning attenuates acute lung injury induced by intestinal ischemia-reperfusion in mice: role of Nrf2.

    Science.gov (United States)

    Meng, Qing-Tao; Cao, Chen; Wu, Yang; Liu, Hui-Min; Li, Wei; Sun, Qian; Chen, Rong; Xiao, Yong-Guang; Tang, Ling-Hua; Jiang, Ying; Leng, Yan; Lei, Shao-Qing; Lee, Chris C; Barry, Devin M; Chen, Xiangdong; Xia, Zhong-Yuan

    2016-10-01

    Intestinal ischemic post-conditioning (IPo) protects against lung injury induced by intestinal ischemia-reperfusion (IIR) partly through promotion of expression and function of heme oxygenase-1 (HO-1). NF-E2-related factor-2 (Nrf2) is a key transcription factor that interacts with HO-1 and regulates antioxidant defense. However, the role of Nrf2 in IPo protection of IIR-induced pulmonary injury is not completely understood. Here we show that IPo significantly attenuated IIR-induced lung injury and suppressed oxidative stress and systemic inflammatory responses. IPo also increased the expression of both Nrf2 and HO-1. Consistently, the beneficial effects of IPo were abolished by ATRA and Brusatol, potent inhibitors of Nrf2. Moreover, the Nrf2 agonist t-BHQ showed similar activity as IPo. Taken together, our data suggest that Nrf2 activity, along with HO-1, plays an important role in the protective effects of IPo against IIR-induced acute lung injury.

  4. Asiaticoside attenuates lipopolysaccharide-induced acute lung injury via down-regulation of NF-κB signaling pathway.

    Science.gov (United States)

    Qiu, Jiaming; Yu, Lijun; Zhang, Xingxing; Wu, Qianchao; Wang, Di; Wang, Xiuzhi; Xia, Cheng; Feng, Haihua

    2015-05-01

    Asiaticoside (AS), a triterpene glycoside isolated from Centella asiatica, has been shown to possess potent anti-inflammatory activity. However, the detailed molecular mechanisms of AS on lipopolysaccharide (LPS)-induced acute lung injury (ALI) model in mice are scanty. The purpose of this study was to evaluate the effect of AS on LPS-induced mouse ALI via down-regulation of NF-κB signaling pathway. We investigated the efficacy of AS on cytokine levels induced by LPS in bronchoalveolar lavage fluid (BALF) and RAW 264.7 cells. The production of cytokine (TNF-α and IL-6) was measured by enzyme-linked immunosorbent assay (ELISA). The lung wet-to-dry weight ratios were measured in LPS-challenged mice, and lung histopathologic changes observed via paraffin section were assessed. To further study the mechanism of AS protective effects on ALI, the activation of NF-κB p65 subunit and the degradation of IκBα were tested by western blot assay. We found that AS treatment at 15, 30 or 45mg/kg dose-dependently attenuated LPS-induced pulmonary inflammation by reducing inflammatory infiltration, histopathological changes, descended cytokine production, and pulmonary edema initiated by LPS. Furthermore, our results suggested that AS suppressed inflammatory responses in LPS-induced ALI through inhibition of the phosphorylation of NF-κB p65 subunit and the degradation of its inhibitor IκBα, and might be a new preventive agent of ALI in the clinical setting.

  5. Acute pancreatitis-induced enzyme release and necrosis are attenuated by IL-1 antagonism through an indirect mechanism.

    Science.gov (United States)

    Fink, G; Yang, J; Carter, G; Norman, J

    1997-01-01

    Interleukin-1 beta (IL-1) is a proinflammatory cytokine which is produced within the pancreas during acute pancreatitis reaching levels which are toxic to many cell types. Since antagonism of this cytokine provides dramatic survival benefits during lethal pancreatitis, we hypothesized that IL-1 had direct secretagogue and cytolytic effects within the pancreas. The effect of IL-1 on pancreatic exocrine function and tissue viability was assessed in vivo by blockade of IL-1 with varying doses of IL-1 receptor antagonist (IL-1ra) prior to the induction of either moderate (caerulein-induced) or severe (choline deficient diet-induced) necrotizing pancreatitis. Subsequent in vitro studies were conducted to determine the direct effect of IL-1 on dispersed rat acini prepared through collagenase digestion. Amylase release was measured after a 30-min incubation with varying doses of recombinant IL-1 beta. Viability was determined in the presence of IL-1 via trypan blue exclusion at multiple time points. Blockade of the IL-1 receptor decreased pancreatic amylase release and tissue necrosis in both models of pancreatitis in a dose-dependent fashion (1.0 mg/kg, P = NS; 10 mg/kg, P amylase release and tissue necrosis are significantly attenuated during experimental pancreatitis by IL-1 antagonism. These changes do not appear to be due to the direct action of IL-1 on pancreatic acini and are likely due to more complex interactions between acini and cytokine-producing leukocytes.

  6. Hepatitis C virus NS3/4A quasispecies diversity in acute hepatitis C infection in HIV-1 co-infected patients.

    Science.gov (United States)

    Nevot, M; Boesecke, C; Parera, M; Andrés, C; Franco, S; Revollo, B; Ingiliz, P; Tural, C; Clotet, B; Rockstroh, J K; Martinez, M A

    2014-06-01

    The growing number of cases of acute hepatitis C (AHC) infections among human immunodeficiency virus type 1 (HIV-1)-positive men who have sex with men (MSM) in the last 10 years has promoted the search for predictors of AHC clearance as well as for epidemiological networks of viral transmission. We characterized the diversity and catalytic efficiency of HCV NS3/4A protease quasispecies in AHC patients coinfected with HIV-1. Plasma samples obtained at HCV diagnosis from 18 MSM HIV-coinfected patients with AHC were studied. Five HCV monoinfected patient samples with AHC were also investigated. An average of 39 clones from each sample was analysed. The catalytic efficiency of the dominant quasispecies (i.e. the most abundant) from each quasispecies was also assayed for mitochondrial antiviral signalling protein (MAVS) cleavage. Phylogenetic analysis identified two clusters of patients with highly related viruses, suggesting a common source of HCV infection. None of the 18 MSM HIV-coinfected patients spontaneously cleared HCV, although 78% of the treated patients achieved a sustained virological response after early treatment with pegylated interferon (pegIFN) plus ribavirin (RBV). The synonymous-nonsynonymous (ds/dn) mutation ratio, a marker of selective pressure, was higher in AHC compared to 26 HIV-1-infected men with genotype 1a chronic hepatitis C (CHC) (P < 0.0001). NS3/4A proteases from AHC patients also exhibited higher catalytic efficiency compared to CHC patients (P < 0.0001). No differences were found when ds/dn mutation ratios and NS3/4A protease catalytic efficiencies from AHC HIV-coinfected patients were compared with AHC monoinfected patients. The presence of epidemiological networks of HCV transmission was confirmed among HIV-1-positive MSM. In addition, substantial genetic diversity was demonstrated in AHC. NS3/4A protease efficiency cleaving MAVS may be associated with virus transmission and response to pegIFN/RBV treatment.

  7. Betaine Treatment Attenuates Chronic Ethanol-Induced Hepatic Steatosis and Alterations to the Mitochondrial Respiratory Chain Proteome

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    Kusum K. Kharbanda

    2012-01-01

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

  8. Epstein-Barr virus associated acute hepatitis with cross-reacting antibodies to other herpes viruses in immunocompetent patients: report of two cases.

    Science.gov (United States)

    Gupta, Ekta; Bhatia, Vikram; Choudhary, Aashish; Rastogi, Archana; Gupta, Naveen L

    2013-03-01

    Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis (IM) which is characterized by the triad of fever, sore throat, and lymphadenopathy. Self-limited, mild liver function test abnormalities are seen in IM. Acute hepatitis in primary EBV infection is uncommon. Serum transaminases are elevated but are less than fivefold the normal levels in most cases and rarely exceed 10 times the normal levels in primary EBV infections especially in elderly. Laboratory diagnosis of acute EBV infection is by serological assays confirming the presence of EBV viral capsid antigen (VCA) IgM antibodies. Due to antigenic cross-reactivity with Herpes viruses, serological assays lack specificity; hence specific molecular diagnostic methods are required for confirmation of the etiology. The present report describes two cases of acute hepatitis caused by infection with EBV which had indistinguishable clinical features and biochemical markers from acute hepatitis caused by hepatotropic viruses such as hepatitis viruses A-E. The diagnosis of infection by EBV was confirmed by detection of EBV DNA in blood of both the patients and EBV DNA in the liver tissue of one of the patients.

  9. Gut microbiota are linked to increased susceptibility to hepatic steatosis in low aerobic capacity rats fed an acute high fat diet

    Science.gov (United States)

    Poor aerobic fitness is linked to nonalcoholic fatty liver disease and increased all-cause mortality. We previously found that low capacity running (LCR) rats fed acute high fat diet (HFD; 45% kcal from fat) for 3 days resulted in positive energy balance and increased hepatic steatosis compared with...

  10. Hepatitis E virus is a leading cause of acute-on-chronic liver disease:experience from a tertiary centre in Bangladesh

    Institute of Scientific and Technical Information of China (English)

    Mamun-Al Mahtab; Salimur Rahman; Mobin Khan; Md. Fazal Karim

    2009-01-01

    BACKGROUND:Acute-on-chronic liver failure (ACLF) is common in Bangladesh. Acute viral E hepatitis is sporadically encountered in this country each year, with a rising incidence in the rainy season. This study aimed to identify the etiology of ACLF in Bangladesh. METHODS:In this retrospective study, 69 ACLF patients were included. They presented to our department at the Bangabandhu Sheikh Mujib Medical University in Dhaka. History of diseases was recorded and appropriate investigations were conducted in all patients. RESULTS:Acute hepatitis E virus (HEV) infection was positive in 21.7% (15/69) of the patients, while 14.5%(10/69) had septicemia. Upper gastrointestinal tract hemorrhage was seen in 4.3% of the patients (3/69), while another 4.3% (3/69) had a positive history for alcohol or drugs. None of the patients tested positive for hepatitis A virus infection and no evidence of hepatitis B virus lfare was found in any patient. No speciifc cause for ACLF could be identiifed. CONCLUSIONS:Acute HEV infection is a leading cause of ACLF in Bangladesh. Many patients were thought to have decompensation of cirrhosis, but subsequently were recognized as having ACLF by a retrospective review according to the deifnition of the Asian Paciifc Association for the Study of the Liver Working Party Meeting on ACLF in New Delhi in early 2008.

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

    NARCIS (Netherlands)

    Geerling, J.J.; Wang, Y.; Havekes, L.M.; Romijn, J.A.; Rensen, P.C.N.

    2013-01-01

    Objective: Central neuropeptide Y (NPY) administration stimulates food intake in rodents. In addition, acute modulation of central NPY signaling increases hepatic production of very low-density lipoprotein (VLDL)-triglyceride (TG) in rats. As hypertriglyceridemia is an important risk factor for athe

  12. Intrathecal morphine attenuates acute opioid tolerance secondary to remifentanil infusions during spinal surgery in adolescents

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    Tripi PA

    2015-09-01

    Full Text Available Paul A Tripi,1 Matthew E Kuestner,1 Connie S Poe-Kochert,2 Kasia Rubin,1 Jochen P Son-Hing,2 George H Thompson,2 Joseph D Tobias3 1Division of Pediatric Anesthesiology, 2Division of Pediatric Orthopaedic Surgery, Rainbow Babies and Children's Hospital, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, 3Department of Anesthesiology and Pain Medicine, Nationwide Children's Hospital, Columbus, OH, USA Introduction: The unique pharmacokinetic properties of remifentanil with a context-sensitive half-life unaffected by length of infusion contribute to its frequent use during anesthetic management during posterior spinal fusion in children and adolescents. However, its intraoperative administration can lead to increased postoperative analgesic requirements, which is postulated to be the result of acute opioid tolerance with enhancement of spinal N-methyl-D-aspartate receptor function. Although strategies to prevent or reduce tolerance have included the coadministration of longer acting opioids or ketamine, the majority of these studies have demonstrated little to no benefit. The current study retrospectively evaluates the efficacy of intrathecal morphine (ITM in preventing hyperalgesia following a remifentanil infusion.Methods: We retrospectively analyzed 54 patients undergoing posterior spinal fusion with segmental spinal instrumentation, to evaluate the effects of ITM on hyperalgesia from remifentanil. Patients were divided into two groups based on whether they did or did not receive remifentanil during the surgery: no remifentanil (control group (n=27 and remifentanil (study group (n=27. Data included demographics, remifentanil dose and duration, Wong–Baker visual analog scale postoperative pain scores, and postoperative intravenous morphine consumption in the first 48 postoperative hours.Results: The demographics of the two study groups were similar. There were no differences in the Wong–Baker visual analog

  13. Sulfur dioxide attenuates LPS-induced acute lung injury via enhancing polymorphonuclear neutrophil apoptosis

    Institute of Scientific and Technical Information of China (English)

    Hui-jie MA; Xin-li HUANG; Yan LIU; Ya-min FAN

    2012-01-01

    Aim:We speculated that the enhanced apoptosis of polymorphonuclear neutrophil (PMN) might be responsible for the inhibition of PMN infiltration in the lung.This study was designed to investigate the effects of sulfur dioxide (SO2) on PMN apoptosis in vivo and in vitro,which may mediate the protective action of SO2 on pulmonary diseases.Methods:Acute lung injury (ALI) was induced by intratracheally instillation of lipopolysaccharide (LPS,100 μg/100 g.in 200 μL saline) in adult male SD rats.SO2 solution (25 μmol/kg) was administered intraperitoneally 30 min before LPS treatment.The rats were killed 6 h after LPS treatment.Lung tissues were collected for histopathologic study and SO2 concentration assay.Bronchoalveolar lavage fluid (BALF) was collected for the measurement of PMN apoptosis.For in vitro experiments,rat peripheral blood PMNs were cultured and treated with LPS (30 mg/L) and S02 (10,20 and 30 μmol/L) for 6 h,and apoptosis-related protein expression was detected by Western blotting,and apoptosis rate was measured with flow cytometry.Results:LPS treatment significantly reduced the SO2 concentrations in the lung tissue and peripheral blood,as compared with the control group.Pretreatment with SO2 prevented LPS-induced reduction of the SO2 concentration in the lung tissue and peripheral blood.LPS treatment significantly reduced PMN apoptosis both in vivo and in vitro,which could be prevented by the pretreatment with SO2.The protein levels of caspase-3 and Bax was significantly increased,but Bcl-2 was decreased by the pretreatment with SO2,as compared with LPS administration alone.Conclusion:SO2 plays an important role as the modulator of PMN apoptosis during LPS-induced ALl,which might be one of the mechanisms underlying the protective action of SO2 on pulmonary diseases.

  14. Effect of hepatic glucose production on acute insulin resistance induced by lipid-infusion in awake rats

    Institute of Scientific and Technical Information of China (English)

    Ling Li; Gang-Yi Yang

    2004-01-01

    AIM: To explore the influence of hepatic glucose production on acute insulin resistance induced by a lipid infusion in awake rats.METHODS: A hyperinsulinaemic-euglycaemic clamp was established in awake chronically catheterized rats. Two groups of rats were studied either with a 4-h intraarterial infusion of lipid/heparin or saline. Insulin-mediated peripheral and hepatic glucose metabolism was assessed by hyperinsulinaemiceuglycaemic clamp combined with [3-3H]-glucose infusion.RESULTS: During hyperinsulinaemic-euglycaemic clamp,there was a significant increase in plasma free fatty acid (FFA, from 741.9±50.6 to 2346.4±238.5 μmol/L, P<0.01) in lipid-infused group. The glucose infusion rates (GIR) in the lipid infusion rats, compared to control rats, were significantly reduced (200-240 min average: lipid infusion; 12.6±1.5 vs control; 34.0±1.6 mg/kg.min, P<0.01), declining to - 35%of the corresponding control values during the last time of the clamp (240 min: lipid infusion; 12.0±1.9 vs control;34.7±1.7 mg/kg.min, P<0.0001). At the end of clamp study,the hepatic glucose production (HGP) in control rats was significantly suppressed (88%) from 19.0±4.5 (basal) to 2.3±0.9 mg/kg.min (P<0.01). The suppressive effect of insulin on HGP was significantly blunted in the lipid-infused (P<0.05). The rate of glucose disappearance (GRd) was a slight decrease in the lipid-infused rats compared with controls during the clamp.CONCLUSION: These data suggest that lipid infusion could induces suppression of hepatic glucose production, impairs the abilities of insulin to suppress lipolysis and mediate glucose utilization in peripheral tissue. Therefore, we conclude that lipid-infusion induces an acute insulin resistance in vivo.

  15. Branched chain amino acid transaminase and branched chain alpha-ketoacid dehydrogenase activity in the brain, liver and skele­tal muscle of acute hepatic failure rats

    Directory of Open Access Journals (Sweden)

    Takei,Nobuyuki

    1985-02-01

    Full Text Available Branched chain amino acid (BCAA transaminase activity increased in both the mitochondrial and supernatant fractions of brain from hepatic failure rats, in which a partial hepatectomy was performed 24h following carbon tetrachloride (CCl4 administration, although the activity of liver and skeletal muscle was the same as in control rats. The elevation of mitochondrial BCAA transaminase activity in liver-injured rats was partly due to increased activity of brain specific Type III isozyme. Branched chain alpha-ketoacid (BCKA dehydrogenase in the brain homogenates was not significantly altered in acute hepatic failure rats, while the liver enzyme activity was markedly diminished. BCKA dehydrogenase activity in the brain homogenates was inhibited by adding ATP to the assay system, and was activated in vitro by preincubating the brain homogenate at 37 degrees C for 15 min. These findings suggest that brain BCAA catabolism is accelerated in acute hepatic failure rats.

  16. Full-Breadth Analysis of CD8+ T-Cell Responses in Acute Hepatitis C Virus Infection and Early Therapy

    Science.gov (United States)

    Lauer, Georg M.; Lucas, Michaela; Timm, Joerg; Ouchi, Kei; Kim, Arthur Y.; Day, Cheryl L.; zur Wiesch, Julian Schulze; Paranhos-Baccala, Glaucia; Sheridan, Isabelle; Casson, Deborah R.; Reiser, Markus; Gandhi, Rajesh T.; Li, Bin; Allen, Todd M.; Chung, Raymond T.; Klenerman, Paul; Walker, Bruce D.

    2005-01-01

    Multispecific CD8+ T-cell responses are thought to be important for the control of acute hepatitis C virus (HCV) infection, but to date little information is actually available on the breadth of responses at early time points. Additionally, the influence of early therapy on these responses and their relationships to outcome are controversial. To investigate this issue, we performed comprehensive analysis of the breadth and frequencies of virus-specific CD8+ T-cell responses on the single epitope level in eight acutely infected individuals who were all started on early therapy. During the acute phase, responses against up to five peptides were identified. During therapy, CD8+ T-cell responses decreased rather than increased as virus was controlled, and no new specificities emerged. A sustained virological response following completion of treatment was independent of CD8+ T-cell responses, as well as CD4+ T-cell responses. Rapid recrudescence also occurred despite broad CD8+ T-cell responses. Importantly, in vivo suppression of CD3+ T cells using OKT3 in one subject did not result in recurrence of viremia. These data suggest that broad CD8+ T-cell responses alone may be insufficient to contain HCV replication, and also that early therapy is effective independent of such responses. PMID:16189000

  17. Hepatic Interferon-λ3 (IFNL3 Gene Expression Reveals Not to Be Attenuated in Non-Favorable IFNL3 rs4803217 or IFNL4 rs368234815 Minor Allele Carriers in Chronic Hepatitis C.

    Directory of Open Access Journals (Sweden)

    Ahmad Amanzada

    Full Text Available Genetic polymorphisms in the region of the interferon-λ genes (IFNL associate with clearance of hepatitis C virus (HCV infection. One of these polymorphisms, IFNL4 rs368234815, determines loss or gain of function of the IFNL4 gene by frameshift variation. The very same and a second one, IFNL3 rs4803217, are supposed to impact the expression of IFNL3: while IFNL4 rs368234815 is suggested to modulate IFNL3 transcription, IFNL3 rs4803217 is thought to alter IFNL3 mRNA stability. The latter process is believed to be partially driven by an HCV-induced ectopic expression of myosin heavy chain genes 7B and 7 and their co-expressed microRNAs mir499 and mir208B. These ideas are evidenced by functional investigations on peripheral blood mononuclear and hepatoma cells in culture. Our study aimed at exploring IFNL3 gene expression in clinical samples, i.e., in ex vivo derived liver tissue from patients with chronic hepatitis C (n = 57 and various other diseases (n = 56. By applying an assay designed to specifically quantify IFNL3 and discriminating paralogous IFNL2 transcripts, IFNL3 mRNA expression was not found to differ significantly between chronic hepatitis C and control samples. Among patients with chronic HCV infection, moreover, IFNL3 rs4803217 or IFNL4 rs368234815 minor alleles did not associate with reduced IFNL3 gene expression. Finally, myosin heavy chain genes 7B and 7 and corresponding microRNAs mir499 and mir208B were not found activated in liver in chronic HCV infection. Of note, detectability of MYH7 mRNA related to the procedure of liver biopsy sampling, as tissue obtained by direct punctation of the liver during laparoscopic inspection was less likely to contain MYH7 transcripts than samples acquired by percutaneous punctation. In conclusion, data on ex vivo derived liver tissue samples argue against an attenuating impact of IFNL3 rs4803217 or IFNL4 rs368234815 minor alleles on hepatic IFNL3 gene expression in vivo.

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

    Science.gov (United States)

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

    2015-06-01

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

  19. Live Attenuated Vaccine Based on Duck Enteritis Virus against Duck Hepatitis A Virus Types 1 and 3

    Science.gov (United States)

    Zou, Zhong; Ma, Ji; Huang, Kun; Chen, Huanchun; Liu, Ziduo; Jin, Meilin

    2016-01-01

    As causative agents of duck viral hepatitis, duck hepatitis A virus type 1 (DHAV-1) and type 3 (DHAV-3) causes significant economic losses in the duck industry. However, a licensed commercial vaccine that simultaneously controls both pathogens is currently unavailable. Here, we generated duck enteritis virus recombinants (rC-KCE-2VP1) containing both VP1 from DHAV-1 (VP1/DHAV-1) and VP1 from DHAV-3 (VP1/DHAV-3) between UL27 and UL26. A self-cleaving 2A-element of FMDV was inserted between the two different types of VP1, allowing production of both proteins from a single open reading frame. Immunofluorescence and Western blot analysis results demonstrated that both VP1 proteins were robustly expressed in rC-KCE-2VP1-infected chicken embryo fibroblasts. Ducks that received a single dose of rC-KCE-2VP1 showed potent humoral and cellular immune responses and were completely protected against challenges of both pathogenic DHAV-1 and DHAV-3 strains. The protection was rapid, achieved as early as 3 days after vaccination. Moreover, viral replication was fully blocked in vaccinated ducks as early as 1 week post-vaccination. These results demonstrated, for the first time, that recombinant rC-KCE-2VP1 is potential fast-acting vaccine against DHAV-1 and DHAV-3. PMID:27777571

  20. Brivanib attenuates hepatic fibrosis in vivo and stellate cell activation in vitro by inhibition of FGF, VEGF and PDGF signaling.

    Directory of Open Access Journals (Sweden)

    Ikuo Nakamura

    Full Text Available Brivanib is a selective inhibitor of vascular endothelial growth factor receptor (VEGFR and fibroblast growth factor receptor (FGFR tyrosine kinases, which are both involved in mechanisms of liver fibrosis. We hypothesized that inhibition of VEGFR and FGFR by brivanib would inhibit liver fibrosis. We therefore examined the effect of brivanib on liver fibrosis in three mouse models of fibrosis.In vivo, we induced liver fibrosis by bile duct ligation (BDL, chronic carbon tetrachloride (CCl4, and chronic thioacetamide (TAA administration. Liver fibrosis was examined by immunohistochemistry and Western immunoblotting. In vitro, we used LX-2 human hepatic stellate cells (HSCs to assess the effect of brivanib on stellate cell proliferation and activation.After in vivo induction with BDL, CCl4, and TAA, mice treated with brivanib showed reduced liver fibrosis and decreased expression of collagen Iα1 and α-smooth muscle actin in the liver. In vitro, brivanib decreased proliferation of HSCs induced by platelet-derived growth factor (PDGF, VEGF, and FGF. Brivanib also decreased stellate cell viability and inhibited PDGFBB-induced phosphorylation of its cognate receptor.Brivanib reduces liver fibrosis in three different animal models and decreases human hepatic stellate cell activation. Brivanib may represent a novel therapeutic approach to treatment of liver fibrosis and prevention of liver cancer.

  1. Blocking Cyclic Adenosine Diphosphate Ribose-mediated Calcium Overload Attenuates Sepsis-induced Acute Lung Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    Qian-yi Peng; Yu Zou; Li-Na Zhang; Mei-Lin Ai; Wei Liu; Yu-Hang Ai

    2016-01-01

    Background:Acute lung injury (ALI) is a common complication of sepsis that is associated with high mortality.Intracellular Ca2+ overload plays an important role in the pathophysiology of sepsis-induced ALI,and cyclic adenosine diphosphate ribose (cADPR) is an important regulator of intracellular Ca2+ mobilization.The cluster of differentiation 38 (CD38)/cADPR pathway has been found to play roles in multiple inflammatory processes but its role in sepsis-induced ALI is still unknown.This study aimed to investigate whether the CD38/cADPR signaling pathway is activated in sepsis-induced ALI and whether blocking cADPR-mediated calcium overload attenuates ALI.Methods:Septic rat models were established by cecal ligation and puncture (CLP).Rats were divided into the sham group,the CLP group,and the CLP+ 8-bromo-cyclic adenosine diphosphate ribose (8-Br-cADPR) group.Nicotinamide adenine dinucleotide (NAD+),cADPR,CD38,and intracellular Ca2+ levels in the lung tissues were measured at 6,12,24,and 48 h after CLP surgery.Lung histologic injury,tumor necrosis factor (TNF)-α,malondialdehyde (MDA) levels,and superoxide dismutase (SOD) activities were measured.Results:NAD+,cADPR,CD38,and intracellular Ca2+ levels in the lungs of septic rats increased significantly at 24 h after CLP surgery.Treatment with 8-Br-cADPR,a specific inhibitor of cADPR,significantly reduced intracellular Ca2+ levels (P =0.007),attenuated lung histological injury (P =0.023),reduced TNF-α and MDA levels (P < 0.001 and P =0.002,respectively) and recovered SOD activity (P =0.031) in the lungs of septic rats.Conclusions:The CD38/cADPR pathway is activated in the lungs of septic rats,and blocking cADPR-mediated calcium overload with 8-Br-cADPR protects against sepsis-induced ALI.

  2. Galunisertib (LY2157299), a transforming growth factor-β receptor I kinase inhibitor, attenuates acute pancreatitis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Liu, X. [Department of General Surgery, the Affiliated Hospital of Qingdao University, Qingdao (China); Department of General Surgery, People' s Hospital of Chengyang, Qingdao (China); Yu, M. [Department of Clinical Laboratory, the Women and Children' s Hospital of Qingdao, Qingdao (China); Chen, Y. [Department of Traditional Chinese Medicine, the Affiliated Hospital of Qingdao University, Qingdao (China); Zhang, J. [Department of General Surgery, the Affiliated Hospital of Qingdao University, Qingdao (China)

    2016-08-08

    Galunisertib (LY2157299), a selective ATP-mimetic inhibitor of TGF-β receptor I (TGF-βRI), is the only known TGF-β pathway inhibitor. In the present study, we investigated the effect of galunisertib on taurocholate (TAC)-induced acute pancreatitis (AP) in rats, and the role of TGF-β and NF-κB signaling pathways. AP was induced by infusion of TAC into the pancreatic duct of Sprague-Dawley male rats (n=30). The rats (220±50 g) were administered galunisertib intragastrically [75 mg·kg{sup -1}·day{sup -1} for 2 days (0 and 24 h)]. Serum IL-1β, IL-6, TNF-α, amylase (AMY), lipase (LIP), and myeloperoxidase (MPO) levels were measured by ELISA. NF-κB activity was detected by electrophoretic mobility shift assay (EMSA); NF-κBp65 and TGF-β1 proteins, as well as TGF-βRI and p-Smad2/3 proteins, were detected by western blot assay. Cell apoptosis was detected by TUNEL assay. H&E staining was used to evaluate the histopathological alterations of the pancreas. Galunisertib treatment attenuated the severity of AP and decreased the pancreatic histological score. In addition, number of apoptotic cells were significantly increased in the galunisertib-treated group (16.38±2.26) than in the AP group (8.14±1.27) and sham-operated group (1.82±0.73; P<0.05 and P<0.01, respectively). Galunisertib decreased the expression levels of TGF-βRI and p-Smad2/3 and inhibited NF-κB activation and p65 translocation compared with the sham-operated group. Furthermore, serum IL-1β, IL-6, TNF-α, AMY and LIP levels and tissue MPO activity were significantly decreased in the galunisertib-treated group. Our data demonstrate that galunisertib attenuates the severity of TAC-induced experimental AP in rats by inducing apoptosis in the pancreas, inhibiting the activation of TGF-β signals and NF-κB as well as the secretion of pro-inflammatory cytokines.

  3. Acute hepatitis A in an elderly patient after care worker travel to high endemicity country.

    Science.gov (United States)

    Aasheim, Erlend T; Seymour, Martin; Balogun, Koye; Ngui, Siew-Lin; Williams, Chris J; Shankar, Ananda Giri

    2013-11-01

    Hepatitis A virus (HAV) is considered one of the most important vaccine-preventable diseases in travelers. HAV spreads from person to person via the fecal-oral route and gives rise to an estimated 1.4 million cases worldwide each year. In developing countries with poor sanitary conditions people tend to be infected during childhood and have few symptoms, whereas in developed countries with good sanitary conditions fewer people develop immunity during childhood. This leads to susceptible populations of adults, who are also more prone to severe complications. Here we describe two confirmed cases of hepatitis A associated with a nursing home. The index case was a care worker who had recently traveled to a high-endemicity country, and the second case was a resident at the nursing home where the index case worked. Both cases had an identical genotype IIIA strain, consistent with a transmission event. Current policy does not include a requirement for hepatitis A vaccine in care workers who travel to high endemicity countries despite the fact that infected care workers can potentially spread the disease to elderly patients and other groups at risk of severe complications from HAV infection. We suggest that employers should consider hepatitis A vaccine upon employment; particularly in care workers who plan to visit areas where HAV is known to be endemic.

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

    NARCIS (Netherlands)

    Duivenvoorden, [No Value; Teusink, B; Rensen, PCN; Kuipers, F; Romijn, JA; Havekes, LM; Voshol, PJ

    2005-01-01

    Hepatic VLDL and glucose production is enhanced in type 2 diabetes and associated with hepatic steatosis. Whether the derangements in hepatic metabolism are attributable to steatosis or to the increased availability of FA metabolites is not known. We used methyl palmoxirate ( MP), an inhibitor of ca

  5. Low Cerebral Oxygen Consumption and Blood Flow in Patients With Cirrhosis and an Acute Episode of Hepatic Encephalopathy

    DEFF Research Database (Denmark)

    Iversen, Peter; Bak, Lasse Kristoffer; Waagepetersen, Helle Sønderby

    2009-01-01

    BACKGROUND & AIMS: It is unclear whether patients with hepatic encephalopathy (HE) have disturbed brain oxygen metabolism and blood flow. METHODS: We measured cerebral oxygen metabolism rate (CMRO(2)) by using (15)O-oxygen positron emission tomography (PET), and cerebral blood flow (CBF) by using....../min in patients with HE, 0.47 +/- 0.02 in patients without HE, and 0.49 +/- 0.03 in healthy subjects. CMRO(2) and CBF were correlated, and both variables correlated negatively with arterial ammonia concentration. Analysis of regional values, using individual magnetic resonance co-registrations, showed...... that the reductions in CMRO(2) and CBF in patients with HE were essentially generalized throughout the brain. CONCLUSIONS: The observations imply that reduced cerebral oxygen consumption and blood flow in cirrhotic patients with an acute episode of overt HE are associated with HE and not cirrhosis as such...

  6. Acute Disseminated Encephalomyelitis following Vaccination against Hepatitis B in a Child: A Case Report and Literature Review

    Science.gov (United States)

    Yuan, Jun-liang; Wang, Shuang-kun; Guo, Xiao-juan

    2016-01-01

    Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system, which has been associated with several vaccines such as rabies, diphtheria-tetanus-polio, smallpox, measles, mumps, rubella, Japanese B encephalitis, pertussis, influenza, and the Hog vaccine. Here, we presented a case of 12-year-old child who suffered from ADEM three weeks after hepatitis B vaccination. He was admitted to our hospital with symptoms of weakness of limbs, high fever, and alteration of consciousness. Some abnormalities were also found in CSF. Treatment with high-dose corticosteroids and intravenous immunoglobulin had significant effect, with marked improvement of the clinical symptoms and the results of CSF. The findings of MRI also detected some abnormal lesions located in both brain and spinal cord. The clinical features, the findings of CSF and MRI, and therapeutic effect may contribute to such diagnosis of ADEM. PMID:27478662

  7. Acute Disseminated Encephalomyelitis following Vaccination against Hepatitis B in a Child: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Jun-liang Yuan

    2016-01-01

    Full Text Available Acute disseminated encephalomyelitis (ADEM is an inflammatory demyelinating disease of the central nervous system, which has been associated with several vaccines such as rabies, diphtheria-tetanus-polio, smallpox, measles, mumps, rubella, Japanese B encephalitis, pertussis, influenza, and the Hog vaccine. Here, we presented a case of 12-year-old child who suffered from ADEM three weeks after hepatitis B vaccination. He was admitted to our hospital with symptoms of weakness of limbs, high fever, and alteration of consciousness. Some abnormalities were also found in CSF. Treatment with high-dose corticosteroids and intravenous immunoglobulin had significant effect, with marked improvement of the clinical symptoms and the results of CSF. The findings of MRI also detected some abnormal lesions located in both brain and spinal cord. The clinical features, the findings of CSF and MRI, and therapeutic effect may contribute to such diagnosis of ADEM.

  8. High doses of bifendate elevate serum and hepatic triglyceride levels in rabbits and mice: animal models of acute hypertriglyceridemia

    Institute of Scientific and Technical Information of China (English)

    Si-yuan PAN; Rong YANG; Yi-fan HAN; Hang DONG; Xu-dong FENG; Na LI; Wei GENG; Kam-ming KO

    2006-01-01

    Aim: To investigate the effects of bifendate on serum and hepatic lipids level in rabbits and mice. Methods: Animals were administered bifendate [powdered pill suspended in 0.5% sodium carboxymethylcellulose (CMC)] at increasing doses (0.25-1 g/kg, ig). Blood lipid and apolipoprotein levels were measured using commercially available assay kits. Results: The treatment of rabbits with a single dose of bifendate (0.3 g/kg) caused a time-dependent and biphasic change in serum triglyceride (TG) levels, with the value reaching a maximum (3-fold increase compared to the baseline value) between 24 and 36 h post-dosing. When mice were orally treated with bifendate (0.25-1 g/kg), serum TG levels increased by 39%-76% and 14%-39% at 24 and 48 h post-dosing, respectively. When given at daily doses of 0.25 and 1 g/kg for 4 d, bifendate increased serum TG levels (56%-79%), with concomitant elevations in apolipoprotein A-I and apolipoprotein B levels at 24 h after the last dosing. TG levels were also increased (11%-43%) in liver samples of mice receiving single or multiple doses of bifendate. However, bifendate treatment caused slight reductions in serum and hepatic total cholesterol levels (9%-13%). The hypertriglyceridemia induced by bifendate was ameliorated by fenofibrate but not inositol nicotinate treatment in mice. Conclusion: The findings suggest that bifendate treatment at high oral doses can cause an acute elevation in serum and hepatic TG levels.

  9. Acute hepatitis C in persons infected with the human immunodeficiency virus (HIV: The "Real-life Setting" proves the concept

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    Obermeier M

    2011-05-01

    Full Text Available Abstract Objectives Outbreaks of sexually transmitted acute HCV infection have been described recently in several cities in the western world. The epidemic affects mainly MSM who are coinfected with HIV and is supposably linked to certain sexual risk practices. Here, we compared our findings with current knowledge and recommendations. Methods HIV-positive patients with the diagnosis of acute HCV infection were included in the retrospective analysis. The patients came from outpatient infectious disease centers in northern German cities. We looked at markers of HIV and HCV infection and compared patients who received treatment and those who did not. Treated patients were followed up to 72 weeks. Results Three hundred nineteen HIV-positive patients with the diagnosis of acute hepatitis C between 2001 and 2008 and were included in the analysis. All patients were male, 315 (99% patients were of caucasian origin, 296 (93% declared homosexual contacts as a risk factor for HCV infection, intravenous drug use was declared in 3 (1% cases. Median age at HCV diagnosis was 40 years (range 20-69 years. Median HCV viral load was 1.2 × 106 IU/mL, 222 patients (70% had HCV genotype 1, 59 (18% genotype 4. The median time of HIV infection was 5.5 years (range 0 to 22.4 years. Median HIV viral load was 110 copies/mL (range 25 to 10 × 106 copies/mL. The median CD 4 count was 461 cells/mm3 (range 55- 1331 cells/mm3. Two hundred and fourty-six patients (77% received anti-HCV treatment, and 175 (55% had completed therapy by the time of the analysis. Median treatment duration was 33 weeks (IQR 24.1-49.9. 93 of the 175 treated patients (53% reached a sustained virological response (SVR. In the multivariate analysis, ART at diagnosis, HCV RNA drop at week 12, hemoglobin levels and higher platelets were associated with SVR. Treatment duration was significantly higher in the SVR group (40.6 weeks vs 26.6 weeks, p Conclusions Our findings confirm that acute hepatitis C in

  10. Added value of arterial enhancement fraction color maps for the characterization of small hepatic low-attenuating lesions in patients with colorectal cancer.

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    Mina Park

    Full Text Available To assess the added value of arterial enhancement fraction (AEF color maps for the differentiation of small metastases from hepatic benign lesions.We retrospectively analyzed 46 patients with colorectal cancer who underwent multiphasic liver CT imaging and had low-attenuating liver lesions smaller than 3 cm (123 total lesions; metastasis: benign = 32:91. AEF color maps of the liver were created from multiphasic liver CT images using dedicated software. Two radiologists independently reviewed multiphasic CT image sets alone and in combination with image sets with AEF color maps using a five-point scale. The additional diagnostic value of the color maps was assessed by means of receiver-operating characteristic (ROC analysis.The area under the ROC curve (Az increased when multiphasic CT images were combined with AEF color map analysis as compared with evaluation based only on multiphasic CT images (from 0.698 to 0.897 for reader 1, and from 0.825 to 0.945 for reader 2; P < 0.001 and 0.002, respectively. The increase Az was especially significant for lesions less than 1 cm (from 0.702 to 0.888 for reader 1, and from 0.768 to 0.958 for reader 2; P = 0.001 and P = 0.001, respectively. The mean AEF of tumor-adjacent parenchyma (35.07 ± 27.2 was significantly higher than that of tumor-free liver parenchyma (27.3 ± 20.6 (P = 0.04.AEF color mapping can improve the diagnostic performance for small hepatic metastases from colorectal cancer and may allow for the elimination of additional examinations.

  11. Galectin-9 and IL-21 mediate cross-regulation between Th17 and Treg cells during acute hepatitis C.

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    Hassen Kared

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

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

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    Kamran Qureshi

    2014-01-01

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

  13. Acute sensorineural hearing loss associated with peginterferon and ribavirin combination therapy during hepatitis C treatment: Outcome after resumption of therapy

    Institute of Scientific and Technical Information of China (English)

    Victor K Wong; Cindy Cheong-Lee; Jo-Ann E Ford; Eric M Yoshida

    2005-01-01

    Peginterferon and ribavirin combination therapy for the treatment of hepatitis C virus (HCV) is well known to be associated with significant adverse effects. Sensorineural hearing loss, that in most cases is unilateral, has been reported as a consequence of therapy with both non-pegylated and pegylated interferon (pegIFN) but is not a well-known adverse effect. We report a 45-year-old Caucasian woman who developed acute sensorineural hearing loss 2 mo after starting therapy with pegIFN-α 2b and ribavirin for the treatment of chronic HCV, genotype 1a. She did not report the hearing loss to the hepatitis clinic until L mo,later whereupon therapy was promptly discontinued.Although her serum alanine aminotransferase (ALT)normalized and her HCV-RNA became undetectable after 12 wk of pegIFN and ribavirin therapy, after discontinuation,her HCV-RNA became detectable with significant elevations of serum ALT. Four months after initial discontinuation,the patient re-commenced pegIFN and ribavirin combination therapy. After 44 of 48 wk of therapy, the patient's liver biochemistry has normalized and the HCV-RNA is undetectable. She has not developed worsening of her hearing loss and hearing on the left-side is unaffected.Both patients and physicians should be aware that sensorineural hearing loss may occur with pegIFN therapy.Our experience suggests that re-institution of therapy is not always associated with further hearing impairment.

  14. Protective effect of danhong injection on acute hepatic failure induced by lipopolysaccharide and d-galactosamine in mice.

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

    2014-01-01

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

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

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    Ying Wang

    2014-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  17. Role of Protective Effect of L-Carnitine against Acute Acetaminophen Induced Hepatic Toxicity in Adult Albino Rats

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    Zeinab M. Gebaly* and Gamal M. Aboul Hassan

    2012-10-01

    Full Text Available Background: Acetaminophen, a widely used analgesic and antipyretic is known to cause hepatic injury in humans and experimental animals when administered in high doses. It was reported that toxic effects of acetaminophen are due to oxidative reactions that take place during its metabolism. L-carnitine is a cofactor in the transfer of long-chain fatty acid allowing to the beta-oxidation of fatty acid in the mitochondria. It is a known antioxidant with protective effects against lipid peroxidation. This study aimed to investigate the possible beneficial effect of L-carnitine as an antioxidant agent against acetaminophen induced hepatic toxicity in rats. Material and Methods: Four rat groups (N=7 in each group. Group I is the control, group II received 500 mg/kg/ body weight of L-carnitine for 7 days by oral route, group III received 640/kg/ bw of acetaminophen by oral route, group IV acute acetaminophen group pretreated with L-carnitine for 7 days by gastric tube gavage tube. The liver of all rats were removed for investigation using light and electro microscopic studies. Results: Acetaminophen caused massive centrilobular necrosis and massive degenerative changes. The electron-microscopic study showed few mitochondria, increased fat droplets and scanty smooth endoplasmic reticulum (SER, rough endoplasmic reticulum (RER.These changes were reduced by L-carnitine pretreatment. Conclusion: those results suggest that acetaminophen results damage in the liver as an acute effect and L-carnitine ameliorated the adverse effects of acetaminophen via its antioxidant role

  18. Acute pancreatitis associated with acute viral hepatitis: case report and review of literature Pancreatite aguda associada com hepatite A aguda: relato de caso e revisão da literatura

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    Danilo Bora Moleta

    2009-12-01

    Full Text Available This case report, along with the review presented, describes a patient diagnosed with acute viral hepatitis, who developed a framework of intense abdominal pain and laboratorial alterations compatible with acute pancreatitis. The association of acute pancreatitis complicating fulminant and non-fulminant acute hepatitis virus (AHV has been reported and several mechanisms have been proposed for this complication, but so far none is clearly involved. As acute hepatitis is a common disease, it is important to stimulate the development of other studies in order to determine local incidence and profile of patients presenting this association in our environment.Este relato de caso, junto com a revisão de literatura, descreve um paciente com diagnóstico de hepatite viral aguda, que desenvolveu quadro de dor abdominal intensa e alterações laboratoriais compatíveis com pancreatite aguda. Casos de pancreatite aguda complicando hepatites virais agudas fulminantes e não fulminantes tem sido esporadicamente relatados e vários mecanismos são propostos para explicar esta complicação, no entanto sua causa ainda se mantém desconhecida. Como a hepatite aguda é doença comum, é importante estimular o desenvolvimento de mais estudos na América Latina que visem determinar a incidência local e o perfil dos pacientes que apresentam esta complicação.

  19. Acute onset anarthria without hepatic manifestation: a rare presentation of Wilson disease

    OpenAIRE

    Verma, Rajesh; Bhandari, Aveg; Tiwari, Navin; Chaudhari, Tejendra S

    2013-01-01

    Wilson disease (WD) is one of the few inherited but treatable disorder mainly affecting the liver and brain resulting in severe disability or death if left untreated. Hence, it is important to keep a high index of suspicion for diagnosing this clinical entity in appropriate clinical settings. The clinical presentation can be quite variable and they may present solely with neurological features sans hepatic symptoms. Such neurological manifestations usually follow subacute to chronic course. A...

  20. Pathological research on acute hepatic and renal tissue damage in Wistar rats induced by cocoa

    Institute of Scientific and Technical Information of China (English)

    Chiedozie Onyejiaka Ibegbulem; Paul Chidoka Chikezie; Ezeikel Chinemerem Dike

    2016-01-01

    Objective: To ascertain the functional integrity of renal and hepatic tissues of Wistar rats fed with processed cocoa bean-based beverages and raw cocoa bean products-containing diets by using biochemical and histological methods. Methods: Thirty Wistar rats were designated on the basis of experimental diets which were given for 28 days. At the end of the feeding period, blood samples were drawn, and renal and hepatic tissues were excised from the experimental rat groups for functional tests and histological examinations, respectively. Results: Serum alanine aminotransferase activities of the experimental rat groups showed no significant difference (P > 0.05) and were within a relatively narrow range of (32.17 ± 4.98) IU/L to (41.00 ± 10.85) IU/L, whereas serum aspartate aminotransferase activities gave wide variation within the range of (15.67 ± 2.13) IU/L to (34.83 ± 8.31) IU/L with P Conclusions: The pattern of alanine aminotransferase activity being more active than aspartate aminotransferase one in serum appeared to correlate with the extent of disar-rangement of hepatic tissue architecture. The experimental rat groups exhibited no hyperbilirubinemia. Also, diets containing processed cocoa bean and raw cocoa bean products did not substantially interfere with the capacity of the hepatocytes to bio-synthesize plasma proteins and the functionality of renal tissues.

  1. Successful Antiviral Triple Therapy in a Longstanding Refractory Hepatitis C Virus Infection with an Acute Kidney Injury

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    David Callau Monje

    2014-01-01

    Full Text Available Introduction. The HCV infection is a common disease with many chronically infected patients worldwide. So far, the standard therapy of a chronic HCV infection consisted of interferon as single therapy or in combination with ribavirin. After approval of the two protease inhibitors, boceprevir and telaprevir, the standard therapy for patients with genotype 1 changed. In patients with acute kidney injury (AKI these therapies are not approved and have so far not been evaluated in studies. Case Report. In April 2012, a 58-year-old female was admitted due to a cryoglobulin-positive chronic HCV infection which had been treated with interferon and ribavirin. Currently, the patient was admitted because of severe complications with an acute kidney injury. We treated our patient successfully with a boceprevir based triple therapy. Conclusion. Limited data suggests that a therapy with ribavirin in patients with AKI seems to be safe under close monitoring. Our patient was treated successfully with a protease inhibitor based triple therapy. Nevertheless, it is necessary to plan an interventional study to evaluate the exact risk-benefit profile of triple therapy regimens in patients with AKI and hepatitis C.

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

    Science.gov (United States)

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

    2014-08-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  4. Different attenuated phenotypes of GM2 gangliosidosis variant B in Japanese patients with HEXA mutations at codon 499, and five novel mutations responsible for infantile acute form.

    Science.gov (United States)

    Tanaka, Akemi; Hoang, Lan Thi Ngcok; Nishi, Yasuaki; Maniwa, Satoshi; Oka, Makio; Yamano, Tsunekazu

    2003-01-01

    Eight mutations of the alpha subunit of beta-hexosaminidase A gene ( HEXA) were identified in eight patients with GM2 gangliosidosis variant B. They were five missense mutations, two splice-site mutations, and one two-base deletion. Five of them, R252L (CGT-->CTT), N295S (AAT-->AAC), W420C (TGG-->TGT), IVS 13, +2A-->C, and del 265-266AC (exon 2), were novel mutations responsible for infantile acute form of GM2 gangliosidosis. Two missense mutations, R499H and R499C, were found in one allele of two patients with attenuated phenotypes. The patient with R499C showed a late infantile form, and the other patient with R499H showed a juvenile form. These two mutations have been reported previously in the patients of other ethnic groups, and they have been known to cause attenuated phenotypes. The milder phenotypes of GM2 gangliosidosis variant B, different from the infantile acute form, have not been reported so far in Japan, and this is the first report of Japanese patients with attenuated phenotypes and their molecular analysis.

  5. Autoimmune hepatitis.

    Science.gov (United States)

    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.

  6. A Novel Matrine Derivative WM130 Inhibits Activation of Hepatic Stellate Cells and Attenuates Dimethylnitrosamine-Induced Liver Fibrosis in Rats

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    Yang Xu

    2015-01-01

    Full Text Available Activation of hepatic stellate cells (HSCs is a critical event in process of hepatic fibrogenesis and cirrhosis. Matrine, the active ingredient of Sophora, had been used for clinical treatment of acute/chronic liver disease. However, its potency was low. We prepared a high potency and low toxicity matrine derivate, WM130 (C30N4H40SO5F, which exhibited better pharmacological activities on antihepatic fibrosis. This study demonstrated that WM130 results in a decreased proliferative activity of HSC-T6 cells, with the half inhibitory concentration (IC50 of 68 μM. WM130 can inhibit the migration and induce apoptosis in HSC-T6 cells at both concentrations of 68 μM (IC50 and 34 μM (half IC50. The expression of α-SMA, Collagen I, Collagen III, and TGF-β1 could be downregulated, and the protein phosphorylation levels of EGFR, AKT, ERK, Smad, and Raf (p-EGFR, p-AKT, p-ERK, p-Smad, and p-Raf were also decreased by WM130. On the DMN-induced rat liver fibrosis model, WM130 can effectively reduce the TGF-β1, AKT, α-SMA, and p-ERK levels, decrease the extracellular matrix (ECM formation, and inhibit rat liver fibrosis progression. In conclusion, this study demonstrated that WM130 can significantly inhibit the activation of HSC-T6 cells and block the rat liver fibrosis progression by inducing apoptosis, suppressing the deposition of ECM, and inhibiting TGF-β/Smad and Ras/ERK pathways.

  7. Acute exercise reduces hepatic glucose production through inhibition of the Foxo1/HNF-4alpha pathway in insulin resistant mice.

    Science.gov (United States)

    De Souza, Cláudio T; Frederico, Marisa J S; da Luz, Gabrielle; Cintra, Dennys E; Ropelle, Eduardo R; Pauli, José R; Velloso, Lício A

    2010-06-15

    Protein hepatocyte nuclear factor 4alpha (HNF-4alpha) is atypically activated in the liver of diabetic rodents and contributes to hepatic glucose production. HNF-4alpha and Foxo1 can physically interact with each other and represent an important signal transduction pathway that regulates the synthesis of glucose in the liver. Foxo1 and HNF-4alpha interact with their own binding sites in the phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) promoters, and this binding is required for their effects on those promoters. However, the effect of physical activity on the HNF-4alpha/Foxo1 pathway is currently unknown. Here, we investigate the protein levels of HNF-4alpha and the HNF-4alpha/Foxo1 pathway in the liver of leptin-deficient (ob/ob) and diet-induced obese Swiss (DIO) mice after acute exercise. The ob/ob and DIO mice swam for four 30 min periods, with 5 min rest intervals for a total swimming time of 2h. Eight hours after the acute exercise protocol, the mice were submitted to an insulin tolerance test (ITT) and determination of biochemical and molecular parameters. Acute exercise improved insulin signalling, increasing insulin-stimulated Akt and Foxo1 phosphorylation and decreasing HNF-4alpha protein levels in the liver of DIO and ob/ob mice under fasting conditions. These phenomena were accompanied by a reduction in the expression of gluconeogenesis genes, such as PEPCK and G6Pase. Importantly, the PI3K inhibitor LY292004 reversed the acute effect of exercise on fasting hyperglycaemia, confirming the involvement of the PI3K pathway. The present study shows that exercise acutely improves the action of insulin in the liver of animal models of obesity and diabetes, resulting in increased phosphorylation and nuclear exclusion of Foxo1, and a reduction in the Foxo1/HNF-4alpha pathway. Since nuclear localization and the association of these proteins is involved in the activation of PEPCK and G6Pase, we believe that the regulation of Foxo1

  8. Hepatitis A virus-encoded miRNAs attenuate the accumulation of viral genomic RNAs in infected cells.

    Science.gov (United States)

    Shi, Jiandong; Sun, Jing; Wu, Meini; Hu, Ningzhu; Hu, Yunzhang

    2016-06-01

    The establishment of persistent infection with hepatitis A virus (HAV) is the common result of most HAV/cell culture systems. Previous observations show that the synthesis of viral RNAs is reduced during infection. However, the underlying mechanism is poorly understood. We characterized three HAV-encoded miRNAs in our previous study. In this study, we aim to investigate the impact of these miRNAs on the accumulation of viral RNAs. The results indicated that the synthesis of viral genomic RNAs was dramatically reduced (more than 75 % reduction, P < 0.05) when transfected with one or two viral miRNA mimics. Conversely, they were significantly increased (more than 3.3-fold addition, P < 0.05) when transfected with one or two viral miRNA inhibitors. The luciferase reporter assay of miRNA targets showed that viral miRNAs were fully complementary to specific sites of the viral plus or minus strand RNA and strongly inhibited their expressions. Further data showed that the relative abundance of viral genomic RNA fragments that contain miRNA targets was also dramatically reduced (more than 80 % reduction, P < 0.05) when viral miRNAs were overexpressed with miRNA mimics. In contrast, they were significantly increased (approximately 2-fold addition, P < 0.05) when viral miRNAs were inhibited with miRNA inhibitors. In conclusion, these data suggest a possible mechanism for the reduction of viral RNA synthesis during HAV infection. Thus, we propose that it is likely that RNA virus-derived miRNA could serve as a self-mediated feedback regulator during infection.

  9. Inhibition of secretory phospholipase A2 activity attenuates acute cardiogenic pulmonary edema induced by isoproterenol infusion in mice after myocardial infarction.

    Science.gov (United States)

    Kawabata, Kenichi; Fujioka, Daisuke; Kobayashi, Tsuyoshi; Saito, Yukio; Obata, Jun-Ei; Nakamura, Takamitsu; Yano, Toshiaki; Watanabe, Kazuhiro; Watanabe, Yosuke; Mishina, Hideto; Kugiyama, Kiyotaka

    2010-10-01

    Several types of secretory phospholipase A2 (sPLA2) are expressed in lung tissue, yielding various eicosanoids that might cause pulmonary edema. This study examined whether inhibition of sPLA2 activity attenuates acute cardiogenic pulmonary edema in mice. Acute cardiogenic pulmonary edema was induced in C57BL/6J male mice by an increase in heart rate with continuous intravenous infusion of isoproterenol (ISP) (10 mg/kg/h) at 2 weeks after the creation of myocardial infarction by left coronary artery ligation. Just before ISP infusion, a single intraperitoneal injection of 100 mg/kg LY374388, a prodrug of LY329722 that inhibits sPLA2 activity, or vehicle was administered. The ISP infusion after myocardial infarction induced interstitial and alveolar edema on lung histology. Furthermore, it increased the lung-to-body weight ratio, pulmonary vascular permeability evaluated by the Evans blue extravasation method, lung activity of sPLA2, and lung content of thromboxane A2 and leukotriene B4. These changes were significantly attenuated by LY374388 treatment. In Kaplan-Meier analysis, the survival rate during the ISP infusion after myocardial infarction was significantly higher in LY374388- than in vehicle-treated mice. Similar results were obtained with another inhibitor of sPLA2 activity, para-bromophenacyl bromide. In conclusion, inhibition of sPLA2 activity suppressed acute cardiogenic pulmonary edema.

  10. Atrial natriuretic peptide attenuates inflammatory responses on oleic acid-induced acute lung injury model in rats

    Institute of Scientific and Technical Information of China (English)

    ZHU Yao-bin; ZHANG Yan-bo; LIU Dong-hai; LI Xiao-feng; LIU Ai-jun; FAN Xiang-ming; QIAO Chen-hui

    2013-01-01

    Background An inflammatory response leading to organ dysfunction and failure continues to be a major problem after injury in many clinical conditions such as sepsis,severe burns,and trauma.It is increasingly recognized that atrial natriuretic peptide (ANP) possesses a broad range of biological activities,including effects on endothelial function and inflammation.A recent study has revealed that ANP exerts anti-inflammatory effects.In this study we tested the effects of human ANP (hANP) on lung injury in a model of oleic acid (OA)-induced acute lung injury (ALl) in rats.Methods Rats were randomly assigned to three groups (n=6 in each group).Rats in the control group received a 0.9% solution of NaCl (1 ml.kg1.h-1) by continuous intravenous infusion,after 30 minutes a 0.9% solution of NaCl (1 ml/kg) was injected intravenously,and then the 0.9% NaCl infusion was restarted.Rats in the ALl group received a 0.9% NaCl solution (1 ml·kg-1·h-1) intravenous infusion,after 30 minutes OA was injected intravenously (0.1 ml/kg),and then the 0.9% NaCl infusion was restarted.Rats in the hANP-treated ALI group received a hANP (0.1μg·kg-1·min-1) infusion,after 30 minutes OA was injected intravenously (0.1 ml/kg),and then the hANP infusion was restarted.The anti-inflammation effects of hANP were evaluated by histological examination and determination of serum cytokine levels.Results Serum intedeukin (IL)-1β,IL-6,IL-10 and tumor necrosis factor (TNF) α were increased in the ALI group at six hours.The levels of all factors were significantly lower in the hANP treated rats (P <0.005).Similarly,levels of IL-1β,IL-6,IL-10 and TNF-α were higher in the lung tissue in the ALI group at six hours.hANP treatment significantly reduced the levels of these factors in the lungs (P <0.005).Histological examination revealed marked reduction in interstitial congestion,edema,and inflammation.Conclusion hANP can attenuate inflammation in an OA-induced lung injury in rat model.

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

    NARCIS (Netherlands)

    Swelm, R.P.L. van; Laarakkers, J.M.M.; Blous, L.; Peters, J.G.P.; Blaney Davidson, E.N.; Kraan, P.M. van der; Swinkels, D.W.; Masereeuw, R.; Russel, F.G.M.

    2012-01-01

    Acetaminophen (APAP), a major cause of acute liver injury in the Western world, is mediated by metabolism and oxidative stress. Recent studies have suggested a role for iron in potentiating APAP-induced liver injury although its regulatory mechanism is not completely understood. The current study wa

  12. Acute exercise reduces insulin resistance-induced TRB3 expression and amelioration of the hepatic production of glucose in the liver of diabetic mice.

    Science.gov (United States)

    Lima, Athos F; Ropelle, Eduardo R; Pauli, José R; Cintra, Dennys E; Frederico, Marisa J S; Pinho, Ricardo A; Velloso, Lício A; De Souza, Cláudio T

    2009-10-01

    TRB3 (a mammalian homolog of Drosophila) is emerging as an important player in the regulation of insulin signaling. TRB3 can directly bind to Ser/Thr protein kinase Akt, the major downstream kinase of insulin signaling. Conversely, physical exercise has been linked to improved glucose homeostasis and enhanced insulin sensitivity; however, the molecular mechanisms by which exercise improves glucose homeostasis, particularly in the hepatic tissue, are only partially known. Here, we demonstrate that acute exercise reduces fasting glucose in two models diabetic mice. Western blot analysis showed that 8 h after a swimming protocol, TRB3 expression was reduced in the hepatic tissue from diet-induced obesity (Swiss) and leptin-deficient (ob/ob) mice, when compared with respective control groups at rest. In parallel, there was an increase in insulin responsiveness in the canonical insulin-signaling pathway in hepatic tissue from DIO and ob/ob mice after exercise. In addition, the PEPCK expression was reduced in the liver after the exercise protocol, suggesting that acute exercise diminished hepatic glucose production through insulin-signaling restoration. Thus, these results provide new insights into the mechanism by which physical activity improves glucose homeostasis in type 2 diabetes.

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

    Directory of Open Access Journals (Sweden)

    Akhtar Jaweed

    2010-05-01

    Full Text Available Abstract Background Liver injury due to dengue viral infection is not uncommon. Acute liver injury is a severe complicating factor in dengue, predisposing to life-threatening hemorrhage, Disseminated Intravascular Coagulation (DIC and encephalopathy. Therefore we sought to determine the frequency of hepatitis in dengue infection and to compare the outcome (length of stay, in hospital mortality, complications between patients of Dengue who have mild/moderate (ALT 23-300 IU/L v/s severe acute hepatitis (ALT > 300 IU/L. Methods A Cohort study of inpatients with dengue viral infection done at Aga Khan University Hospital Karachi. All patients (≥ 14 yrs age admitted with diagnosis of Dengue Fever (DF, Dengue Hemorrhagic Fever (DHF or Dengue Shock Syndrome (DSS were included. Chi square test was used to compare categorical variables and fischer exact test where applicable. Survival analysis (Cox regression and log rank for primary outcome was done. Student t test was used to compare continuous variables. A p value of less than or equal to 0.05 was taken as significant. Results Six hundred and ninety nine patients were enrolled, including 87% (605 patients with DF and 13% (94 patients with DHF or DSS. Liver functions tests showed median ALT of 88.50 IU/L; IQR 43.25-188 IU/L, median AST of 174 IU/L; IQR 87-371.5 IU/L and median T.Bil of 0.8 mg/dl; IQR 0.6-1.3 mg/dl. Seventy one percent (496 had mild to moderate hepatitis and 15% (103 had severe hepatitis. Mean length of stay (LOS in patients with mild/moderate hepatitis was 3.63 days v.s 4.3 days in those with severe hepatitis (P value 0.002. Overall mortality was 33.3% (n = 6 in mild/moderate hepatitis vs 66.7% (n = 12 in severe hepatitis group (p value Conclusion Severe hepatitis (SGPT>300IU in Dengue is associated with prolonged LOS, mortality, bleeding and RF.

  14. Fatal acute myocarditis and fulminant hepatic failure in an infant with pandemic human influenza A, H1N1 (2009) virus infection