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Sample records for direct hepatic differentiation

  1. Hepatic abscess versus peripheral cholangiocarcinoma: Sonographic differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Hwan Hoon; Kim, Yun Hwan; Kang, Chang Ho; Chung, Kyoo Byung; Suh, Won Hyuck [Korea University College of Medicine, Seoul (Korea, Republic of); Lee, Chang Hee [Kunkuk University College of Medicine, Chung-Ju Hospital, Chung-Ju (Korea, Republic of)

    2000-12-15

    To find out the sonographic findings that are useful to differentiate hepatic abscess from peripheral cholangiocarcinoma. Twenty-two hepatic abscesses and 22 peripheral cholangiocarcinomas which had been confirmed histologically were included in this study. Objective points were echo characteristics of the lesion, internal septation, presence of peripheral low echoic rim, demarcation from normal liver(well or poorly defined), posterior enhancement, multiplicity, dilatation of bile duct(obstructive or non-obstructive), intrahepatic duct stone, pleural effusion, and intra-abdominal fluid collection. Echo characteristics of the lesion were classified in-to four types. Type I; Predominantly echogenic with hypoechoic portion, type II; Echogenic without hypoechoic portion, type III; Predominantly hypoechoic with echogenic portion, type IV; Hypoechoic without echogenic portion. 1)Nine abscesses and 2 peripheral cholangiocarcinomas were type I(p=0.037), 2)One abscess and 18 peripheral cholangiocarcinomas were type II(p=0.001), 3)Seven abscesses and none of peripheral cholangiocarcinomas were type III(p=0.001), 4)Five abscesses and 2 peripheral cholangiocarcinomas were type IV(p=0.410). Only 7 abscesses showed internal septations(p=0.013). One abscess and 9 peripheral cholangiocarcinomas showed peripheral hypoechoic halos(p=0.012). Only 9 peripheral cholangiocarcinomas showed obstructive bile duct dilatation (p=0.001). There were no statistically significant differences between abscess and peripheral cholangiocarcinoma on other objective points. Predominantly echogenic with hypoechoic portion, predominantly hypoechoic with echogenic portion, and internal septation are the features suggestive of hepatic abscess, and echogenic without hypoechoic portion, peripheral hypoechoic halo, obstructive bile duct dilatation are suggestive of peripheral cholangiocarcinoma. Therefore these sonographic findings are helpful to differentiate hepatic abscess from peripheral

  2. Differential effect of gender on hepatic fat

    International Nuclear Information System (INIS)

    Gilsanz, Vicente; Chung, Sandra A.; Kaplowitz, Neil

    2011-01-01

    There are discrepant data on whether men or women have a higher risk for hepatic steatosis. To examine the influence of gender on hepatic adiposity in teenagers and young adults. We measured subcutaneous abdominal fat (SAF), intra-abdominal fat (IAF) and hepatic tissue density (a surrogate measure of hepatic fat) using CT in 505 healthy teenagers and young adults (254 males, 251 females; ages 15-22.9 years). Overall, compared to men, women had higher values of SAF (P 0.05). When compared to overweight and obese young women, overweight and obese young men are at greater risk for hepatic steatosis, independent of IAF. (orig.)

  3. Hepatic differentiation potential of commercially available human mesenchymal stem cells.

    Science.gov (United States)

    Ong, Shin-Yeu; Dai, Hui; Leong, Kam W

    2006-12-01

    The ready availability and low immunogenicity of commercially available mesenchymal stem cells (MSC) render them a potential cell source for the development of therapeutic products. With cell source a major bottleneck in hepatic tissue engineering, we investigated whether commercially available human MSC (hMSC) can transdifferentiate into the hepatic lineage. Based on previous studies that find rapid gain of hepatic genes in bone marrow-derived stem cells cocultured with liver tissue, we used a similar approach to drive hepatic differentiation by coculturing the hMSC with rat livers treated or untreated with gadolinium chloride (GdCl(3)). After a 24-hour coculture period with liver tissue injured by GdCl(3) in a Transwell configuration, approximately 34% of the cells differentiated into albumin-expressing cells. Cocultured cells were subsequently maintained with growth factors to complete the hepatic differentiation. Cocultured cells expressed more hepatic gene markers, and had higher metabolic functions and P450 activity than cells that were only differentiated with growth factors. In conclusion, commercially available hMSC do show hepatic differentiation potential, and a liver microenvironment in culture can provide potent cues to accelerate and deepen the differentiation. The ability to generate hepatocyte-like cells from a commercially available cell source would find interesting applications in liver tissue engineering.

  4. Differential effect of gender on hepatic fat

    Energy Technology Data Exchange (ETDEWEB)

    Gilsanz, Vicente [Children' s Hospital Los Angeles, USC, Keck School of Medicine, Department of Radiology, MS 81, Los Angeles, CA (United States); Children' s Hospital Los Angeles, USC, Keck School of Medicine, Department of Pediatrics, Los Angeles, CA (United States); Chung, Sandra A. [Children' s Hospital Los Angeles, USC, Keck School of Medicine, Department of Radiology, MS 81, Los Angeles, CA (United States); Kaplowitz, Neil [USC, Keck School of Medicine, USC Research Center for Liver Disease, Los Angeles, CA (United States)

    2011-09-15

    There are discrepant data on whether men or women have a higher risk for hepatic steatosis. To examine the influence of gender on hepatic adiposity in teenagers and young adults. We measured subcutaneous abdominal fat (SAF), intra-abdominal fat (IAF) and hepatic tissue density (a surrogate measure of hepatic fat) using CT in 505 healthy teenagers and young adults (254 males, 251 females; ages 15-22.9 years). Overall, compared to men, women had higher values of SAF (P < 0.0001) but similar measures of IAF and liver tissue density (P = 0.09 and 0.92, respectively). However, when compared to overweight/obese men, overweight/obese women had strikingly similar IAF values (P = 0.85) but lower hepatic fat (P = 0.009). Multiple regression analyses indicated that, after adjusting for age and SAF, IAF independently predicted hepatic density in males (P < 0.0001) but not in females (P = 0.36). Hepatic fat increased with body mass in males from lean to overweight and obese (P < 0.0001) but not in females (P > 0.05). When compared to overweight and obese young women, overweight and obese young men are at greater risk for hepatic steatosis, independent of IAF. (orig.)

  5. Hepatic Shock Differential Diagnosis and Risk Factors: A Review Article.

    Science.gov (United States)

    Soleimanpour, Hassan; Safari, Saeid; Rahmani, Farzad; Nejabatian, Arezu; Alavian, Seyed Moayed

    2015-10-01

    Liver as an important organ has a vital role in physiological processes in the body. Different causes can disrupt normal function of liver. Factors such as hypo-perfusion, hypoxemia, infections and some others can cause hepatic injury and hepatic shock. Published research resources from 2002 to May 2015 in some databases (PubMed, Scopus, Index Copernicus, DOAJ, EBSCO-CINAHL, Science direct, Cochrane library and Google scholar and Iranian search database like SID and Iranmedex) were investigated for the present study. Different causes can lead to hepatic shock. Most of these causes can be prevented by early resuscitation and treatment of underlying factors. Hepatic shock is detected in ill patients, especially those with hemodynamic disorders. It can be prevented by early treatment of underlying disease. There is no definite treatment for hepatic shock and should be managed conservatively. Hepatic shock in patients can increase the mortality rate.

  6. MR imaging assessment of direct hepatic invasion by adjacent tumors

    International Nuclear Information System (INIS)

    Moeser, P.M.; Karstaedt, N.; Wolfman, N.T.; Bechtold, R.E.

    1986-01-01

    The proper staging of right renal and adrenal tumors requires accurate prediction of hepatic invasion. The authors retrospectively reviewed MR studies of 35 patients with right renal or adrenal masses to assess the utility of MR imaging in predicting direct hepatic invasion. Twenty-three patients were selected for study on the basis of absence of the fat plane between tumor and liver. Hepatic signal and tumor-liver interface characteristics were used to predict invasion. In 14 patients with renal tumors, absence of abnormal signal from hepatic parenchyma correlated well with absence of invasion, but the presence of abnormal hepatic signal did not necessarily indicate hepatic invasion. Inversion-recovery pulse sequences optimally demonstrated abnormal hepatic signal as well as the tumor-liver interface. The authors are currently reviewing the studies in the nine patients with adrenal masses

  7. Direct-acting antivirals for chronic hepatitis C

    DEFF Research Database (Denmark)

    Jakobsen, Janus C; Nielsen, Emil Eik; Feinberg, Joshua

    2017-01-01

    BACKGROUND: Millions of people worldwide suffer from hepatitis C, which can lead to severe liver disease, liver cancer, and death. Direct-acting antivirals (DAAs), e.g. sofosbuvir, are relatively new and expensive interventions for chronic hepatitis C, and preliminary results suggest that DAAs may...... eradicate hepatitis C virus (HCV) from the blood (sustained virological response). Sustained virological response (SVR) is used by investigators and regulatory agencies as a surrogate outcome for morbidity and mortality, based solely on observational evidence. However, there have been no randomised trials...... hepatitis C-related morbidity, serious adverse events, and health-related quality of life. Our secondary outcomes were all-cause mortality, ascites, variceal bleeding, hepato-renal syndrome, hepatic encephalopathy, hepatocellular carcinoma, non-serious adverse events (each reported separately), and SVR. We...

  8. Bioenergetic Changes during Differentiation of Human Embryonic Stem Cells along the Hepatic Lineage

    DEFF Research Database (Denmark)

    Hopkinson, Branden M; Madsen, Claus Desler; Kalisz, Mark

    2017-01-01

    Mitochondrial dysfunction has been demonstrated to result in premature aging due to its effects on stem cells. Nevertheless, a full understanding of the role of mitochondrial bioenergetics through differentiation is still lacking. Here we show the bioenergetics profile of human stem cells...... of embryonic origin differentiating along the hepatic lineage. Our study reveals especially the transition between hepatic specification and hepatic maturation as dependent on mitochondrial respiration and demonstrates that even though differentiating cells are primarily dependent on glycolysis until induction...

  9. Seroprevalence of hiv and hepatitis viruses in directed blood donors ...

    African Journals Online (AJOL)

    Aims: To determine the seroprevalence of HIV and Hepatitis B viruses in directed blood donors in Nguru and also to see if there is co-infection of these viruses in this category of donor population. Method: This is a prospective study carried out at the blood bank of the Federal Medical Centre Nguru, Yobe State between ...

  10. Direct-acting antivirals for chronic hepatitis C

    DEFF Research Database (Denmark)

    Jakobsen, Janus C; Nielsen, Emil Eik; Feinberg, Joshua

    2017-01-01

    and Drug Administration (FDA) (www.fda.gov), and pharmaceutical company sources for ongoing or unpublished trials. Searches were last run in October 2016. SELECTION CRITERIA: Randomised clinical trials comparing DAAs versus no intervention or placebo, alone or with co-interventions, in adults with chronic......BACKGROUND: Millions of people worldwide suffer from hepatitis C, which can lead to severe liver disease, liver cancer, and death. Direct-acting antivirals (DAAs) are relatively new and expensive interventions for chronic hepatitis C, and preliminary results suggest that DAAs may eradicate...

  11. Reactivation of hepatitis B in patients of chronic hepatitis C with hepatitis B virus infection treated with direct acting antivirals.

    Science.gov (United States)

    Yeh, Ming-Lun; Huang, Chung-Feng; Hsieh, Meng-Hsuan; Ko, Yu-Min; Chen, Kuan-Yu; Liu, Ta-Wei; Lin, Yi-Hung; Liang, Po-Cheng; Hsieh, Ming-Yen; Lin, Zu-Yau; Chen, Shinn-Cherng; Huang, Ching-I; Huang, Jee-Fu; Kuo, Po-Lin; Dai, Chia-Yen; Yu, Ming-Lung; Chuang, Wan-Long

    2017-10-01

    Hepatitis B virus (HBV) may reactivate when treating chronic hepatitis C (CHC) with direct acting antivirals (DAA). We aim to investigate the risk of HBV reactivation during DAA therapy. Chronic hepatitis C patients receiving pan-oral DAA therapy from December 2013 to August 2016 were evaluated. Fifty-seven patients that had a past HBV infection (negative hepatitis B surface antigen [HBsAg] and positive hepatitis B core antibody) and seven patients that had a current HBV infection (positive HBsAg) were enrolled. Serum HBV and hepatitis C virus (HCV) markers were regularly measured. The endpoints were the HCV sustained virological response (SVR) and the HBV virological/clinical reactivation. The overall SVR 12 rate was 96.9%, and two patients, one with positive HBsAg, had a relapse of HCV. No episodes of HBV virological reactivation were observed among the patients with a past HBV infection. For the seven patients with a current HBV infection, HBV virological reactivation was found in four (57.1%) of the seven patients. Clinical reactivation of HBV was observed in one patient with pretreatment detectable HBV DNA and recovered after entecavir administration. For the other three patients with HBV virological reactivation, the reappearance of low level HBV DNA without clinical reactivation was observed. HBsAg levels demonstrated only small fluctuations in all the patients. There was a minimal impact of hepatitis B core antibody seropositivity on HCV efficacy and safety. For CHC patients with current HBV infection, the risk of HBV reactivation was present, and monitoring the HBV DNA level during therapy is warranted. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  12. The significance of postangiographic CT for differentiation of hepatic masses

    International Nuclear Information System (INIS)

    Lee, Jae Kyo; Chang, Jae Chun; Chang, You Song

    1994-01-01

    To identify the long term hemodynamics of various hepatic masses and to determine any differential findings by using postangiograpic CT performed with increased amount of contrast media and time than conventional contrast CT. 50 confirmed masses consisted of 22 hepatocellular carcinoma, 10 cholangiocarcinoma, 9 metastasis, and 9 cavernous hemangioma were included. The changes of the density of internal viable tumor portion relative to surrounding normal liver parenchyma in postangiograhic CT from that in conventional CT were classified as 3 patients; no specific changes, increase, or decrease. In 22 cases of hepatocellular carcinoma, six cases showed no relative density change, four cases increase, and twelve cases decrease. In ten cases of cholangiocacinoma, one case showed no change, nine cases increase. In nine cases of metastasis, four cases showed no change, five cases increase. In nine cases of hemangioma, all cases showed increase. In postangiographic CT which emphasize the significance of postequilibrium and delayed phase, other hemodynamic changes undetected in angiography could more easily be comprehended. Considering the differing amount of consumed contrast media and time duration, and with reference of other imaging modalities, differential diagnosis of hepatic masses based on long term hemodynamics could easily be made

  13. Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals.

    Science.gov (United States)

    Ahmed, Asma; Felmlee, Daniel J

    2015-12-18

    There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR) rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.

  14. Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals

    Directory of Open Access Journals (Sweden)

    Asma Ahmed

    2015-12-01

    Full Text Available There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.

  15. Profile of Inflammation-associated genes during Hepatic Differentiation of Human Pluripotent Stem Cells

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    Joseph Ignatius Irudayam

    2015-12-01

    Full Text Available Expression of genes associated with inflammation was analyzed during differentiation of human pluripotent stem cells (PSCs to hepatic cells. Messenger RNA transcript profiles of differentiated endoderm (day 5, hepatoblast (day 15 and hepatocyte-like cells (day 21 were obtained by RNA sequencing analysis. When compared to endoderm cells an immature cell type, the hepatic cells (days 15 and 21 had significantly higher expression of acute phase protein genes including complement factors, coagulation factors, serum amyloid A and serpins. Furthermore, hepatic phase of cells expressed proinflammatory cytokines IL18 and IL32 as well as cytokine receptors IL18R1, IL1R1, IL1RAP, IL2RG, IL6R, IL6ST and IL10RB. These cells also produced CCL14, CCL15, and CXCL- 1, 2, 3, 16 and 17 chemokines. Endoderm cells had higher levels of chemokine receptors, CXCR4 and CXCR7, than that of hepatic cells. Sirtuin family of genes involved in aging, inflammation and metabolism were differentially regulated in endoderm and hepatic phase cells. Ligands and receptors of the tumor necrosis factor (TNF family as well as downstream signaling factors TRAF2, TRAF4, FADD, NFKB1 and NFKBIB were differentially expressed during hepatic differentiation.

  16. Resolution of Hepatic Encephalopathy Following Hepatic Artery Embolization in a Patient with Well-Differentiated Neuroendocrine Tumor Metastatic to the Liver

    International Nuclear Information System (INIS)

    Erinjeri, Joseph P.; Deodhar, Ajita; Thornton, Raymond H.; Allen, Peter J.; Getrajdman, George I.; Brown, Karen T.; Sofocleous, Constantinos T.; Reidy, Diane L.

    2010-01-01

    Hepatic encephalopathy is considered a contraindication to hepatic artery embolization. We describe a patient with a well-differentiated neuroendocrine tumor metastatic to the liver with refractory hepatic encephalopathy and normal liver function tests. The encephalopathy was refractory to standard medical therapy with lactulose. The patient's mental status returned to baseline after three hepatic artery embolization procedures. Arteriography and ultrasound imaging before and after embolization suggest that the encephalopathy was due to arterioportal shunting causing hepatofugal portal venous flow and portosystemic shunting. In patients with a primary or metastatic well-differentiated neuroendocrine tumor whose refractory hepatic encephalopathy is due to portosystemic shunting (rather than global hepatic dysfunction secondary to tumor burden), hepatic artery embolization can be performed safely and effectively.

  17. [IgM class antibodies against hepatitis A viruses in the differentiation of viral hepatitis].

    Science.gov (United States)

    Zivanović-Marinković, V; Stanković, D; Parabucki, S; Lazarov, A; Marinković, V; Krstić, L; Letica, Z

    1982-01-01

    The sera of 64 patients with acute viral hepatitis which were previously HbsAG negative by rPHA were tested by RIA methods for the presence of HBsAG and anti-HBc, by EIA method for HBc and anti-HBc and also by RIA method for the presence of IgM antibodies against hepatitis A virus. The pairs of sera were tested also for the presence of antibodies against cytomegalovirus and EB viruses. Of the total of 64 patients, markers of fresh HB viral infection were proved in 5 patients, sera positive to IgM antibodies to hepatitis A virus were found in 51 and no positive tests to any of the tested viruses were found in 8. The authors consider that they belonged to "non-A, non-B" viral hepatitis.

  18. Direct-acting antiviral therapy for chronic hepatitis C

    NARCIS (Netherlands)

    de Bruijne, J.

    2012-01-01

    Hepatitis C virus (HCV) infection was discovered in the late 1980s. Since then, tremendous progress has been made in understanding the pathophysiology of HCV infection together with the development of improved therapies for patients with chronic hepatitis C. The main focus of this thesis was to

  19. Directional differentiation of chicken embryonic stem cells into ...

    African Journals Online (AJOL)

    Jane

    2011-08-01

    Aug 1, 2011 ... In this study, the differentiation potential of chicken ES cells was investigated ... Key words: Chicken embryonic stem cells, in vitro, directional differentiation, .... synthesized by using the Revert Aid first strand cDNA synthesis kit.

  20. Ultrasonographic differentiation of biliary atresia and neonatal hepatitis: Reestablishment of size criteria of the gallbladder

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Woo Sun; Cheon, Jung Eun; Koh, Young Hwan; Kim, In One; Yeon, Kyung Mo [Seoul National University College of Medicine and Institude of Radiation Medicion, Seoul (Korea, Republic of)

    2001-12-15

    To reestablish the size criterion of the gallbladder on ultrasonography (US) for the differentiation diagnosis of biliary atresia from neonatal hepatitis. Abdominal US ws performed in 201 patients with jaundice and 40 patients without evidence of jaundice or hepatobiliary illness (all with the age less than 4 months). US was performed in fasting (fasting for at least 4 hours) to measure the length of the gallbladder and calculated the area of the gallbladder lumen. The morphology of the gallbladder was classified into three types: normal, elongated and atretic. To evaluate the contractibility of the gallbladder, the length of the gallbladder and area of the gallbladder lumen was again measured 1 hour after feeding. The final diagnosis included biliary atresia in 79 patients and neonatal hepatitis in 83 patients. Differences in the length, area, and morphology of the gallbladder were statistically significant among three groups, the normal group, neonatal hepatitis group and biliary atresia group (length and area of gallbladder; normal group>neonatal hepatitis>biliary atresia). The differences in the length and area of gallbladder between pre- and postmeal state were statistically significant in the normal and neonatal hepatitis groups whereas those of biliary atresia were not significant (p=0.85). When the empirical size criterion of the gallbladder (<15 mm in length) was applied, the sensitivity, specificity and diagnostic accuracy for the differential diagnosis of biliary atresia from hepatitis were 52%, 82%, and 67%, respectively. Meanwhile, if the area criterion(<30 mm{sup 2} in area) was applied, the sensitivity, the specificity and diagnostic accuracy were 67%, 85%, and 75%, respectively. Ultrasonographic evaluation of the morphology as well as size of the gallbladder are helpful in the differential diagnosis of biliary atresia from neonatal hepatitis. Therefore, since the measurement of the area of gallbladder lumen on US reflect both size and morphology of

  1. Differential equations inverse and direct problems

    CERN Document Server

    Favini, Angelo

    2006-01-01

    DEGENERATE FIRST ORDER IDENTIFICATION PROBLEMS IN BANACH SPACES A NONISOTHERMAL DYNAMICAL GINZBURG-LANDAU MODEL OF SUPERCONDUCTIVITY. EXISTENCE AND UNIQUENESS THEOREMSSOME GLOBAL IN TIME RESULTS FOR INTEGRODIFFERENTIAL PARABOLIC INVERSE PROBLEMSFOURTH ORDER ORDINARY DIFFERENTIAL OPERATORS WITH GENERAL WENTZELL BOUNDARY CONDITIONSTUDY OF ELLIPTIC DIFFERENTIAL EQUATIONS IN UMD SPACESDEGENERATE INTEGRODIFFERENTIAL EQUATIONS OF PARABOLIC TYPE EXPONENTIAL ATTRACTORS FOR SEMICONDUCTOR EQUATIONSCONVERGENCE TO STATIONARY STATES OF SOLUTIONS TO THE SEMILINEAR EQUATION OF VISCOELASTICITY ASYMPTOTIC BEHA

  2. Hepatitis

    Science.gov (United States)

    ... most common types of viral hepatitis. What Is Hepatitis A? For kids, hep A is the most common ... they recover, it does not come back. Can Hepatitis A Be Prevented? The following will help keep people ...

  3. Hepatic Mass Caused by Fasciola Hepatica: A Tricky Differential Diagnosis

    Science.gov (United States)

    Yılmaz, Bülent; Köklü, Seyfettin; Gedikoğlu, Gökhan

    2013-01-01

    Fascioliasis is a zoonotic infestation caused by the trematode fasciola hepatica. It presents a wide spectrum of clinical pictures ranging from fever and eosinophilia to ambiguous gastrointestinal symptoms in the acute phase. However, it may often be overlooked, especially in the acute phase, because of uncertain symptoms. Fasciola hepatica can have an initial presentation similar to the presentation of malignancy. Here, we report a case of a hepatic mass caused by fasciola hepatica. PMID:24080633

  4. The impact of share wave elastography in differentiation of hepatic hemangioma from malignant liver tumors in pediatric population

    International Nuclear Information System (INIS)

    Özmen, Evrim; Adaletli, İbrahim; Kayadibi, Yasemin; Emre, Şenol; Kılıç, Fahrettin; Dervişoğlu, Sergülen; Kuruğoğlu, Sebuh; Şenyüz, Osman Faruk

    2014-01-01

    Highlights: • We evaluated the impact of share wave elastography technique in differentiation hepatic hemangiomas from malignant liver tumors in pediatric population. • Share wave technique can increase the diagnostic capability of conventional ultrasonography in the differential diagnosis of liver tumors in children. • Share wave elastography is a potential adjunctive diagnostic technique for pediatric liver tumors. - Abstract: Objective: In children it is crucial to differentiate malignant liver tumors from the most common benign tumor, hepatic hemangiomas since the treatment strategies are quite different. We aimed to evaluate the efficiency of shear wave elastography (SWE) technique in differentiation of malignant hepatic tumors and hepatic hemangiomas. Methods: Twenty patients with hepatic tumor were included in our study. Two radiologists performed SWE for 13 patients with malignant hepatic tumors including hepatoblastoma (n = 7), hepatocellular carcinoma (n = 3), metastasis (n = 2), embryonal sarcoma (n = 1) and 7 patients with hepatic hemangioma. All of our patients were between the age of 1 and 192 months (mean age: 56.88 months). Receiver operating characteristic analysis was achieved to evaluate the diagnostic accuracy of SWE and to determine the optimal cut-off value in differentiation hepatic hemangioma from malignant hepatic tumors. Results: The mean SWE values (in kPa) for the first observer were 46.94 (13.8–145) and 22.38 (6.6–49.6) and those for the second observer were 57.91 (11–237) and 23.87 (6.4–57.5), respectively for malignant hepatic tumors and hepatic hemangiomas. The SWE values of malignant hepatic tumors were significantly higher than those of hepatic hemangioma (p = 0.02). The inter-observer agreement was almost perfect (0.81). The area under the receiver operating characteristic curve of SWE for differentiating the hepatic hemangioma from malignant hepatic tumors was 0.77 with a sensitivity of 72.7% and a specificity of 66

  5. 75 FR 55797 - Draft Guidance for Industry on Chronic Hepatitis C Virus Infection: Developing Direct-Acting...

    Science.gov (United States)

    2010-09-14

    ...] Draft Guidance for Industry on Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral... entitled ``Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Agents for Treatment... announcing the availability of a draft guidance for industry entitled ``Chronic Hepatitis C Virus Infection...

  6. Hepatic differentiation of human pluripotent stem cells in miniaturized format suitable for high-throughput screen

    Directory of Open Access Journals (Sweden)

    Arnaud Carpentier

    2016-05-01

    Full Text Available The establishment of protocols to differentiate human pluripotent stem cells (hPSCs including embryonic (ESC and induced pluripotent (iPSC stem cells into functional hepatocyte-like cells (HLCs creates new opportunities to study liver metabolism, genetic diseases and infection of hepatotropic viruses (hepatitis B and C viruses in the context of specific genetic background. While supporting efficient differentiation to HLCs, the published protocols are limited in terms of differentiation into fully mature hepatocytes and in a smaller-well format. This limitation handicaps the application of these cells to high-throughput assays. Here we describe a protocol allowing efficient and consistent hepatic differentiation of hPSCs in 384-well plates into functional hepatocyte-like cells, which remain differentiated for more than 3 weeks. This protocol affords the unique opportunity to miniaturize the hPSC-based differentiation technology and facilitates screening for molecules in modulating liver differentiation, metabolism, genetic network, and response to infection or other external stimuli.

  7. Contemporary issues and future directions in autoimmune hepatitis.

    Science.gov (United States)

    Liberal, Rodrigo; Mieli-Vergani, Giorgina; Vergani, Diego

    2016-06-03

    Autoimmune hepatitis (AIH) is a severe life-threatening hepatopathy of unknown etiology, affecting both pediatric and adult populations, and characterised by inflammatory liver histology, circulating non-organ-specific autoantibodies, and hypergammaglobulinaemia. AIH is a very heterogeneous disease with a variety of clinical presentations, ranging from asymptomatic liver test abnormalities to acute severe hepatitis or even acute liver failure. It responds very well to immunosuppressive treatment with prednisolone with or without azathioprine. Patients who are intolerant or fail to respond to standard therapy are candidates for alternative immunosuppressive regimens, the combination of steroids with mycophenolate mofetil or calcineurin inhibitors being the most frequently reported. The pathogenesis of AIH remains not completely understood, although there is evidence that genetic predisposition, molecular mimicry and defective immunoregulatory mechanisms contribute to the autoimmune liver damage. A literature search was conducted using the key-words 'autoimmune hepatitis', 'immunogenetics', 'regulatory T-cells' and 'immunosuppression'. The aim of this review is to discuss recent breakthroughs in the understanding AIH pathogenesis, diagnosis and treatment. Expert commentary: Progress in the understanding of AIH pathogenesis is likely to contribute to the development of novel therapeutic strategies, such as the adoptive transfer of autologous expanded antigen-specific regulatory T-cells.

  8. Direct Acting Antivirals in Patients with Chronic Hepatitis C and Down Syndrome

    Directory of Open Access Journals (Sweden)

    Eric R. Yoo

    2016-01-01

    Full Text Available Patients with Down syndrome who received blood transfusions, likely in conjunction with cardiothoracic surgery for congenital heart disease and prior to the implementation of blood-donor screening for hepatitis C virus infection, face a substantial risk of acquiring the infection. In the past, interferon-based therapy for chronic hepatitis C infection in patients with Down syndrome was noted to have lower efficacy and potentially higher risk of adverse effects. Recently, the treatment for chronic hepatitis C has been revolutionized with the introduction of interferon-free direct acting antivirals with favorable safety, tolerability, and efficacy profile. Based on our experiences, the newly approved sofosbuvir-based direct acting antiviral therapy is well tolerated and highly efficacious in this subpopulation of hepatitis C virus infected patients with Down syndrome.

  9. Acoustic Radiation Force Impulse Elastography for Focal Hepatic Tumors: Usefulness for Differentiating Hemangiomas from Malignant Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Eun [Department of Radiology, Gyeongsang National University School of Medicine, Jinju 660-702 (Korea, Republic of); Lee, Jae Young [Department of Radiology and Radiation Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Bae, Kyung Soo [Department of Radiology, Gyeongsang National University School of Medicine, Jinju 660-702 (Korea, Republic of); Han, Joon Koo; Choi, Byung Ihn [Department of Radiology and Radiation Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of)

    2013-07-01

    The purpose of this study is to investigate whether acoustic radiation force impulse (ARFI) elastography with ARFI quantification and ARFI 2-dimensional (2D) imaging is useful for differentiating hepatic hemangiomas from malignant hepatic tumors. One-hundred-and-one tumors in 74 patients were included in this study: 28 hemangiomas, 26 hepatocellular carcinomas (HCCs), three cholangiocarcinomas (CCCs), 20 colon cancer metastases and 24 other metastases. B-mode ultrasound, ARFI 2D imaging, and ARFI quantification were performed in all tumors. Shear wave velocities (SWVs) of the tumors and the adjacent liver and their SWV differences were compared among the tumor groups. The ARFI 2D images were compared with B-mode images regarding the stiffness, conspicuity and size of the tumors. The mean SWV of the hemangiomas was significantly lower than the malignant hepatic tumor groups: hemangiomas, 1.80 ± 0.57 m/sec; HCCs, 2.66 ± 0.94 m/sec; CCCs, 3.27 ± 0.64 m/sec; colon cancer metastases, 3.70 ± 0.61 m/sec; and other metastases, 2.82 ± 0.96 m/sec (p < 0.05). The area under the receiver operating characteristics curve of SWV for differentiating hemangiomas from malignant tumors was 0.86, with a sensitivity of 96.4% and a specificity of 65.8% at a cut-off value of 2.73 m/sec (p < 0.05). In the ARFI 2D images, the malignant tumors except HCCs were stiffer and more conspicuous as compared with the hemangiomas (p < 0.05). ARFI elastography with ARFI quantification and ARFI 2D imaging may be useful for differentiating hepatic hemangiomas from malignant hepatic tumors.

  10. Robust Regression Analysis of GCMS Data Reveals Differential Rewiring of Metabolic Networks in Hepatitis B and C Patients

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    Cedric Simillion

    2017-10-01

    Full Text Available About one in 15 of the world’s population is chronically infected with either hepatitis virus B (HBV or C (HCV, with enormous public health consequences. The metabolic alterations caused by these infections have never been directly compared and contrasted. We investigated groups of HBV-positive, HCV-positive, and uninfected healthy controls using gas chromatography-mass spectrometry analyses of their plasma and urine. A robust regression analysis of the metabolite data was conducted to reveal correlations between metabolite pairs. Ten metabolite correlations appeared for HBV plasma and urine, with 18 for HCV plasma and urine, none of which were present in the controls. Metabolic perturbation networks were constructed, which permitted a differential view of the HBV- and HCV-infected liver. HBV hepatitis was consistent with enhanced glucose uptake, glycolysis, and pentose phosphate pathway metabolism, the latter using xylitol and producing threonic acid, which may also be imported by glucose transporters. HCV hepatitis was consistent with impaired glucose uptake, glycolysis, and pentose phosphate pathway metabolism, with the tricarboxylic acid pathway fueled by branched-chain amino acids feeding gluconeogenesis and the hepatocellular loss of glucose, which most probably contributed to hyperglycemia. It is concluded that robust regression analyses can uncover metabolic rewiring in disease states.

  11. Radioactive sodium selenite in the differentiation of hepatic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Houlder, A E [King Edward VIII Hospital, Durban (South Africa). Dept. of Radiophysics

    1977-06-11

    Selenium-75 selenite and technetium-99m sulphur colloid scans were performed on 38 South African Blacks with intrahepatic space-occupying lesions. Uptake of selenite was demonstrated in the 'cold area' on the sulphur colloid scan in 17 out of 19 patients with hepatocellular carcinoma, but in 16 patients with amoebic liver abscess there was no uptake of selenite in the 'cold area'. In 3 patients with secondary involvement in the liver, 2 had positive uptake of selenite in the affected region. /sup 75/Se selenite was found to be useful in the differential diagnosis of intrahepatic lesions.

  12. Hepatitis C virus induces a prediabetic state by directly impairing hepatic glucose metabolism in mice.

    Science.gov (United States)

    Lerat, Hervé; Imache, Mohamed Rabah; Polyte, Jacqueline; Gaudin, Aurore; Mercey, Marion; Donati, Flora; Baudesson, Camille; Higgs, Martin R; Picard, Alexandre; Magnan, Christophe; Foufelle, Fabienne; Pawlotsky, Jean-Michel

    2017-08-04

    Virus-related type 2 diabetes is commonly observed in individuals infected with the hepatitis C virus (HCV); however, the underlying molecular mechanisms remain unknown. Our aim was to unravel these mechanisms using FL-N/35 transgenic mice expressing the full HCV ORF. We observed that these mice displayed glucose intolerance and insulin resistance. We also found that Glut-2 membrane expression was reduced in FL-N/35 mice and that hepatocyte glucose uptake was perturbed, partly accounting for the HCV-induced glucose intolerance in these mice. Early steps of the hepatic insulin signaling pathway, from IRS2 to PDK1 phosphorylation, were constitutively impaired in FL-N/35 primary hepatocytes via deregulation of TNFα/SOCS3. Higher hepatic glucose production was observed in the HCV mice, despite higher fasting insulinemia, concomitant with decreased expression of hepatic gluconeogenic genes. Akt kinase activity was higher in HCV mice than in WT mice, but Akt-dependent phosphorylation of the forkhead transcription factor FoxO1 at serine 256, which triggers its nuclear exclusion, was lower in HCV mouse livers. These findings indicate an uncoupling of the canonical Akt/FoxO1 pathway in HCV protein-expressing hepatocytes. Thus, the expression of HCV proteins in the liver is sufficient to induce insulin resistance by impairing insulin signaling and glucose uptake. In conclusion, we observed a complete set of events leading to a prediabetic state in HCV-transgenic mice, providing a valuable mechanistic explanation for HCV-induced diabetes in humans. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. 75 FR 11189 - Expanded Access to Direct-Acting Antiviral Agents for the Treatment of Chronic Hepatitis C...

    Science.gov (United States)

    2010-03-10

    ... viral hepatitis and from 70 to 90 percent of all cases of hepatocellular carcinoma. An estimated 3.2...] Expanded Access to Direct-Acting Antiviral Agents for the Treatment of Chronic Hepatitis C Infection in... hepatitis C (CHC) infection in patients with unmet medical need. This public hearing is being held to obtain...

  14. MSCT diagnosis and differential diagnosis of hepatic focal nodular hyperplasia

    International Nuclear Information System (INIS)

    Zhang Haitao; Xu Qinsha; Chen Yutang; Song Yupiao

    2011-01-01

    Objective: To evaluate the MSCT findings of focal nodular hyperplasia (FNH) of the liver, and to improve the diagnostic standard. Methods: The MSCT findings were analyzed retrospectively in 25 patients pathologically approved with FNH. All patients underwent 16 detector row spiral CT scanning with and without contrast enhancement. Results: 28 lesions were discovered by CT, with single lesion showed in 22 cases, 2 lesions showed in 3 cases. All lesions showed a solitary nodules or lobulated mass in the liver. On plain CT, FNH showed equal or slightly low density. In the arterial phase, 27 lesions were vigorously and homogeneously enhanced, except the central scars with CT value of 99∼149HU and the mean CT-number of 124 HU. 1 lesion ws enhanced inter-homogeneously. Tortuous and enlarged arteries were seen at the center or periphery in 8 of the 28 lesions. In the portal venous phase, 16 lesions remained slightly hyperdense, 8 lesions turned to isodense, and 1 lesion turned to slightly hypodense. The typical central scar was showed in 8 lesions and 2 lesions showed delayed enhancement. 21 cases were correctly diagnosed by MSCT, with the diagnostic accuracy of 84.0%. Conclusion: MSCT scanning can fully show the pathologic and the blood supplying characteristics of FNH. The typical FNH can be easily diagnosed by CT, while the atypical cases should be differentiated from hepatocellular carcinoma, hemangioma of liver, liver cell adenoma and fibrolamellar hepatocarcinoma. (authors)

  15. An immunohistochemical approach to differentiate hepatic lipidosis from hepatic phospholipidosis in rats.

    Science.gov (United States)

    Obert, Leslie A; Sobocinski, Gregg P; Bobrowski, Walter F; Metz, Alan L; Rolsma, Mark D; Altrogge, Douglas M; Dunstan, Robert W

    2007-08-01

    Hepatocellular vacuolation can be a diagnostic challenge since cytoplasmic accumulations of various substances (lipid, water, phospholipids, glycogen, and plasma) can have a similar morphology. Cytoplasmic accumulation of phospholipids following administration of cationic amphiphilic drugs (CAD) can be particularly difficult to differentiate from nonphosphorylated lipid accumulations at the light microscopic level. Histochemical methods (Sudan Black, Oil Red-O, Nile Blue, etc.) can be used to identify both nonphosphorylated and/or phosphorylated lipid accumulations, but these techniques require non-paraffin-embedded tissue and are only moderately sensitive. Thus, electron microscopy is often utilized to achieve a definitive diagnosis based upon the characteristic morphologic features of phospholipid accumulations; however, this is a low throughput and labor intense procedure. In this report, we describe the use of immunohistochemical staining for LAMP-2 (a lysosome-associated protein) and adipophilin (a protein that forms the membrane around non-lysosomal lipid droplets) to differentiate phospholipidosis and lipidosis, respectively in the livers of rats. This staining procedure can be performed on formalin-fixed paraffin embedded tissues, is more sensitive than histochemistry, and easier to perform than ultrastructural evaluation.

  16. TRIF Differentially Regulates Hepatic Steatosis and Inflammation/Fibrosis in MiceSummary

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    Ling Yang

    2017-05-01

    Full Text Available Background & Aims: Toll-like receptor 4 (TLR4 signaling is activated through 2 adaptor proteins: MyD88 and TIR-domain containing adaptor-inducing interferon-β (TRIF. TLR4 and MyD88 are crucial in nonalcoholic steatohepatitis (NASH and fibrosis. However, the role of TRIF in TLR4-mediated NASH and fibrosis has been elusive. This study investigated the differential roles of TRIF in hepatic steatosis and inflammation/fibrosis. Methods: A choline-deficient amino acid defined (CDAA diet was used for the mouse NASH model. On this diet, the mice develop hepatic steatosis, inflammation, and fibrosis. TLR4 wild-type and TLR4-/- bone marrow chimeric mice and TRIF-/- mice were fed CDAA or a control diet for 22 weeks. Hepatic steatosis, inflammation, and fibrosis were examined. Results: In the CDAA diet–induced NASH, the mice with wild-type bone marrow had higher alanine aminotransferase and hepatic tumor necrosis factor levels than the mice with TLR4-/- bone marrow. The nonalcoholic fatty liver disease activity score showed that both wild-type and TLR4-/- bone marrow chimeras had reduced hepatic steatosis, and that both types of chimeras had similar levels of inflammation and hepatocyte ballooning to whole-body wild-type mice. Notably, wild-type recipients showed more liver fibrosis than TLR4-/- recipients. Although TRIF-/- mice showed reduced hepatic steatosis, these mice showed more liver injury, inflammation, and fibrosis than wild-type mice. TRIF-/- stellate cells and hepatocytes produced more C-X-C motif chemokine ligand 1 (CXCL1 and C-C motif chemokine ligand than wild-type cells in response to lipopolysaccharide. Consistently, TRIF-/- mice showed increased CXCL1 and CCL3 expression along with neutrophil and macrophage infiltration, which promotes liver inflammation and injury. Conclusions: In TLR4-mediated NASH, different liver cells have distinct roles in hepatic steatosis, inflammation, and fibrosis. TRIF promotes hepatic

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

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    Boix Loreto

    2006-11-01

    Full Text Available Abstract Background Little is known at the molecular level concerning the differences and/or similarities between alcohol and hepatitis C virus induced liver disease. Global transcriptional profiling using oligonucleotide microarrays was therefore performed on liver biopsies from patients with cirrhosis caused by either chronic alcohol consumption or chronic hepatitis C virus (HCV. Results Global gene expression patterns varied significantly depending upon etiology of liver disease, with a greater number of differentially regulated genes seen in HCV-infected patients. Many of the gene expression changes specifically observed in HCV-infected cirrhotic livers were expectedly associated with activation of the innate antiviral immune response. We also compared severity (CTP class of cirrhosis for each etiology and identified gene expression patterns that differentiated ethanol-induced cirrhosis by class. CTP class A ethanol-cirrhotic livers showed unique expression patterns for genes implicated in the inflammatory response, including those related to macrophage activation and migration, as well as lipid metabolism and oxidative stress genes. Conclusion Stages of liver cirrhosis could be differentiated based on gene expression patterns in ethanol-induced, but not HCV-induced, disease. In addition to genes specifically regulating the innate antiviral immune response, mechanisms responsible for differentiating chronic liver damage due to HCV or ethanol may be closely related to regulation of lipid metabolism and to effects of macrophage activation on deposition of extracellular matrix components.

  18. Differential effects of low-fat and high-fat diets on fed-state hepatic triacylglycerol secretion, hepatic fatty acid profiles, and DGAT-1 protein expression in obese-prone Sprague–Dawley rats

    Science.gov (United States)

    Heden, Timothy D.; Morris, E. Matthew; Kearney, Monica L.; Liu, Tzu-Wen; Park, Young-min; Kanaley, Jill A.; Thyfault, John P.

    2015-01-01

    The purpose of this study was to compare the effects of short-term low-fat (LF) and high-fat (HF) diets on fed-state hepatic triacylglycerol (TAG) secretion, the content of proteins involved in TAG assembly and secretion, fatty acid oxidation (FAO), and the fatty acid profile of stored TAG. Using selectively bred obese-prone Sprague–Dawley rats, we directly measured fed-state hepatic TAG secretion, using Tyloxapol (a lipoprotein lipase inhibitor) and a standardized oral mixed meal (45% carbohydrate, 40% fat, 15% protein) bolus in animals fed a HF or LF diet for 2 weeks, after which the rats were maintained on their respective diet for 1 week (washout) prior to the liver being excised to measure protein content, FAO, and TAG fatty acid profiles. Hepatic DGAT-1 protein expression was ~27% lower in HF- than in LF-fed animals (p < 0.05); the protein expression of all other molecules was similar in the 2 diets. The fed-state hepatic TAG secretion rate was ~39% lower (p < 0.05) in HF- (4.62 ± 0.18 mmol·h−1) than in LF- (7.60 ± 0.57 mmol·h−1) fed animals. Hepatic TAG content was ~2-fold higher (p < 0.05) in HF- (1.07 ± 0.15 nmol·g−1 tissue) than in LF- (0.50 ± 0.16 nmol·g−1 tissue) fed animals. In addition, the fatty acid profile of liver TAG in HF-fed animals closely resembled the diet, whereas in LF-fed animals, the fatty acid profile consisted of mostly de novo synthesized fatty acids. FAO was not altered by diet. LF and HF diets differentially alter fed-state hepatic TAG secretion, hepatic fatty acid profiles, and DGAT-1 protein expression. PMID:24669989

  19. Differential effects of low-fat and high-fat diets on fed-state hepatic triacylglycerol secretion, hepatic fatty acid profiles, and DGAT-1 protein expression in obese-prone Sprague-Dawley rats.

    Science.gov (United States)

    Heden, Timothy D; Morris, E Matthew; Kearney, Monica L; Liu, Tzu-Wen; Park, Young-Min; Kanaley, Jill A; Thyfault, John P

    2014-04-01

    The purpose of this study was to compare the effects of short-term low-fat (LF) and high-fat (HF) diets on fed-state hepatic triacylglycerol (TAG) secretion, the content of proteins involved in TAG assembly and secretion, fatty acid oxidation (FAO), and the fatty acid profile of stored TAG. Using selectively bred obese-prone Sprague-Dawley rats, we directly measured fed-state hepatic TAG secretion, using Tyloxapol (a lipoprotein lipase inhibitor) and a standardized oral mixed meal (45% carbohydrate, 40% fat, 15% protein) bolus in animals fed a HF or LF diet for 2 weeks, after which the rats were maintained on their respective diet for 1 week (washout) prior to the liver being excised to measure protein content, FAO, and TAG fatty acid profiles. Hepatic DGAT-1 protein expression was ∼27% lower in HF- than in LF-fed animals (p < 0.05); the protein expression of all other molecules was similar in the 2 diets. The fed-state hepatic TAG secretion rate was ∼39% lower (p < 0.05) in HF- (4.62 ± 0.18 mmol·h(-1)) than in LF- (7.60 ± 0.57 mmol·h(-1)) fed animals. Hepatic TAG content was ∼2-fold higher (p < 0.05) in HF- (1.07 ± 0.15 nmol·g(-1) tissue) than in LF- (0.50 ± 0.16 nmol·g(-1) tissue) fed animals. In addition, the fatty acid profile of liver TAG in HF-fed animals closely resembled the diet, whereas in LF-fed animals, the fatty acid profile consisted of mostly de novo synthesized fatty acids. FAO was not altered by diet. LF and HF diets differentially alter fed-state hepatic TAG secretion, hepatic fatty acid profiles, and DGAT-1 protein expression.

  20. Hepatic Differentiation of Human Induced Pluripotent Stem Cells in a Perfused Three-Dimensional Multicompartment Bioreactor

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    Nora Freyer

    2016-08-01

    Full Text Available The hepatic differentiation of human induced pluripotent stem cells (hiPSC holds great potential for application in regenerative medicine, pharmacological drug screening, and toxicity testing. However, full maturation of hiPSC into functional hepatocytes has not yet been achieved. In this study, we investigated the potential of a dynamic three-dimensional (3D hollow fiber membrane bioreactor technology to improve the hepatic differentiation of hiPSC in comparison to static two-dimensional (2D cultures. A total of 100 × 106 hiPSC were seeded into each 3D bioreactor (n = 3. Differentiation into definitive endoderm (DE was induced by adding activin A, Wnt3a, and sodium butyrate to the culture medium. For further maturation, hepatocyte growth factor and oncostatin M were added. The same differentiation protocol was applied to hiPSC maintained in 2D cultures. Secretion of alpha-fetoprotein (AFP, a marker for DE, was significantly (p < 0.05 higher in 2D cultures, while secretion of albumin, a typical characteristic for mature hepatocytes, was higher after hepatic differentiation of hiPSC in 3D bioreactors. Functional analysis of multiple cytochrome P450 (CYP isoenzymes showed activity of CYP1A2, CYP2B6, and CYP3A4 in both groups, although at a lower level compared to primary human hepatocytes (PHH. CYP2B6 activities were significantly (p < 0.05 higher in 3D bioreactors compared with 2D cultures, which is in line with results from gene expression. Immunofluorescence staining showed that the majority of cells was positive for albumin, cytokeratin 18 (CK18, and hepatocyte nuclear factor 4-alpha (HNF4A at the end of the differentiation process. In addition, cytokeratin 19 (CK19 staining revealed the formation of bile duct-like structures in 3D bioreactors similar to native liver tissue. The results indicate a better maturation of hiPSC in the 3D bioreactor system compared to 2D cultures and emphasize the potential of dynamic 3D culture

  1. Hepatic differentiation of human iPSCs in different 3D models: A comparative study.

    Science.gov (United States)

    Meier, Florian; Freyer, Nora; Brzeszczynska, Joanna; Knöspel, Fanny; Armstrong, Lyle; Lako, Majlinda; Greuel, Selina; Damm, Georg; Ludwig-Schwellinger, Eva; Deschl, Ulrich; Ross, James A; Beilmann, Mario; Zeilinger, Katrin

    2017-12-01

    Human induced pluripotent stem cells (hiPSCs) are a promising source from which to derive distinct somatic cell types for in vitro or clinical use. Existent protocols for hepatic differentiation of hiPSCs are primarily based on 2D cultivation of the cells. In the present study, the authors investigated the generation of hiPSC-derived hepatocyte-like cells using two different 3D culture systems: A 3D scaffold-free microspheroid culture system and a 3D hollow-fiber perfusion bioreactor. The differentiation outcome in these 3D systems was compared with that in conventional 2D cultures, using primary human hepatocytes as a control. The evaluation was made based on specific mRNA expression, protein secretion, antigen expression and metabolic activity. The expression of α-fetoprotein was lower, while cytochrome P450 1A2 or 3A4 activities were higher in the 3D culture systems as compared with the 2D differentiation system. Cells differentiated in the 3D bioreactor showed an increased expression of albumin and hepatocyte nuclear factor 4α, as well as secretion of α-1-antitrypsin as compared with the 2D differentiation system, suggesting a higher degree of maturation. In contrast, the 3D scaffold-free microspheroid culture provides an easy and robust method to generate spheroids of a defined size for screening applications, while the bioreactor culture model provides an instrument for complex investigations under physiological-like conditions. In conclusion, the present study introduces two 3D culture systems for stem cell derived hepatic differentiation each demonstrating advantages for individual applications as well as benefits in comparison with 2D cultures.

  2. Phenobarbital alters hepatic Mrp2 function by direct and indirect interactions

    NARCIS (Netherlands)

    Patel, NJ; Zamek-Gliszczynski, MJ; Zhang, PJ; Han, YH; Jansen, PLM; Meier, PJ; Stieger, B; Brouwer, KLR

    Phenobarbital (PB) treatment impairs the biliary excretion of some organic anions. One mechanism may involve direct competition for biliary excretion by PB and/or a PB metabolite. Alternatively, PB may alter the expression and/or function of hepatic organic anion transport proteins. The role of

  3. Phenobarbital alters hepatic Mrp2 function by direct and indirect interactions

    NARCIS (Netherlands)

    Patel, Nita J.; Zamek-Gliszczynski, Maciej J.; Zhang, Peijin; Han, Yong-Hae; Jansen, Peter L. M.; Meier, Peter J.; Stieger, Bruno; Brouwer, Kim L. R.

    2003-01-01

    Phenobarbital (PB) treatment impairs the biliary excretion of some organic anions. One mechanism may involve direct competition for biliary excretion by PB and/or a PB metabolite. Alternatively, PB may alter the expression and/or function of hepatic organic anion transport proteins. The role of

  4. Differential gene expression analysis of in vitro duck hepatitis B virus infected primary duck hepatocyte cultures

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    Issac Aneesh

    2011-07-01

    Full Text Available Abstract Background The human hepatitis B virus (HBV, a member of the hepadna viridae, causes acute or chronic hepatitis B, and hepatocellular carcinoma (HCC. The duck hepatitis B virus (DHBV infection, a dependable and reproducible model for hepadna viral studies, does not result in HCC unlike chronic HBV infection. Information on differential gene expression in DHBV infection might help to compare corresponding changes during HBV infection, and to delineate the reasons for this difference. Findings A subtractive hybridization cDNA library screening of in vitro DHBV infected, cultured primary duck hepatocytes (PDH identified cDNAs of 42 up-regulated and 36 down-regulated genes coding for proteins associated with signal transduction, cellular respiration, transcription, translation, ubiquitin/proteasome pathway, apoptosis, and membrane and cytoskeletal organization. Those coding for both novel as well as previously reported proteins in HBV/DHBV infection were present in the library. An inverse modulation of the cDNAs of ten proteins, reported to play role in human HCC, such as that of Y-box binding protein1, Platelet-activating factor acetylhydrolase isoform 1B, ribosomal protein L35a, Ferritin, α-enolase, Acid α-glucosidase and Caspase 3, copper-zinc superoxide dismutase (CuZnSOD, Filamin and Pyruvate dehydrogenase, was also observed in this in vitro study. Conclusions The present study identified cDNAs of a number of genes that are differentially modulated in in vitro DHBV infection of primary duck hepatocytes. Further correlation of this differential gene expression in in vivo infection models would be valuable to understand the little known aspects of the hepadnavirus biology.

  5. Mechanism of action of direct-acting antiviral agents in treatment of chronic hepatitis C

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    WEN Xiaoyu

    2016-09-01

    Full Text Available With the development and launch of direct-acting antiviral agents (DAAs in the world in recent years, therapeutic regimens for chronic hepatitis C are constantly evolving. DAAs will also be launched in China in the near future. DAAs mainly target at the non-structural proteins of HCV and can inhibit HCV RNA replication. This article introduces the targets, mechanism of action, and resistance characteristics of different DAAs, as well as their current research and development in China and the results of phase Ⅲ clinical studies, in order to provide a reference for combined therapeutic strategies with DAAs in the treatment for chronic hepatitis C.

  6. Differing results of direct and indirect solid phase radioimmunoassay for HBsAg in acute hepatitis

    International Nuclear Information System (INIS)

    Strohm, W.D.; Legler, K.; Gerlich, W.; Stamm, B.; Zimmer, S.; Biotest-Serum-Institut G.m.b.H., Frankfurt am Main; Goettingen Univ.

    1978-01-01

    In 54 patients suffering from active viral hepatitis the indirect solid phase radioimmunoassay (ind-SPRIA) for HBsAg was positive in 9 cases the direct solid phase radioimmunoassay (d-SPRIA) being negative. In 2 further cases ind-SPRIA was positive during several weeks but d-SPRIA only once. AntiHBc could be detected in 9 of these patients. In 7 patients the usual decrease of the transaminase activity was followed by a second elavation with prolongation of the disease. The unknown factor detected by ind-SPRIA suggests a special of acute hepatitis. (orig.) [de

  7. Differing results of direct and indirect solid phase radioimmunoassay for HBsAg in acute hepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Strohm, W D; Legler, K; Gerlich, W; Stamm, B; Zimmer, S [Frankfurt Univ. (Germany, F.R.). Abt. fuer Gastroenterologie; Biotest-Serum-Institut G.m.b.H., Frankfurt am Main (Germany, F.R.); Goettingen Univ. (Germany, F.R.). Hygiene-Institut)

    1978-09-01

    In 54 patients suffering from active viral hepatitis the indirect solid phase radioimmunoassay (ind-SPRIA) for HBsAg was positive in 9 cases the direct solid phase radioimmunoassay (d-SPRIA) being negative. In 2 further cases ind-SPRIA was positive during several weeks but d-SPRIA only once. AntiHBc could be detected in 9 of these patients. In 7 patients the usual decrease of the transaminase activity was followed by a second elavation with prolongation of the disease. The unknown factor detected by ind-SPRIA suggests a special of acute hepatitis.

  8. Utility of dual echo T2-weighted turbo spin echo MR imaging for differentiation of solid, malignant hepatic lesions from nonsolid, benign hepatic lesions

    International Nuclear Information System (INIS)

    Yang, Dal Mo; Yoon, Myung Hwan; Kim, Hak Soo; Lee, Eun Joo; Kim, Jong Ho; Kim, Hyung Sik; Chung, Jin Woo

    1999-01-01

    To evaluate the additive value of multiphasic contrast-enhanced dynamic MR imaging as a supplement to dual-echo T2-weighted TSE MR imaging for the differentiation of solid, malignant hepatic lesions from nonsolid, benign hepatic lesions. Two radiologists retrospectively reviewed dual-echo T2-weighted TSE MR images and gadolinium-enhanced MR images in 51 patients with hepatic lesions (28 malignant, 69 benign). For the differentiation of malignant from benign lesions, as seen on dual-echo T2-weighted TSE MR images, we evaluated sensitivity, specificity, and accuracy, and compared with the results with those for dual echo T2-weighted MR images plus multiphasic contrast-enhanced dynamic MR images. In addition, Az values for dual echo T2-weighted MR images were compared with those for dual echo T2-weighted MR images plus multiphasic contrast-enhanced dynamic MR images. For the differentiation of malignant from benign hepatic lesions, as seen on dual-echo T2-weighted TSE images, sensitivity, specificity, and accuracy were 80.0%, 97.5%, and 93.9%, respectively, for lesions less than 3cm in diameter, and 92.3%, 95.0%, and 93.5%, respectively, for those that were 3cm or larger. The results for dual-echo T2-weighted MR imaging plus multiphasic contrast-enhanced dynamic MR imaging were 86.7%, 100.0%, and 97.3%, respectively, for lesions less than 3cm, and 92.3%, 100.0%, and 95.7%, respectively for those that were 3cm or larger. There were no significant differences in sensitivity, specificity, or accuracy between the results obtained using dual-echo T2-weighted MR imaging and those obtained with dual-echo T2-weighted MR imaging plus multiphasic contrast-enhanced dynamic MR imaging. Nor were these statistically significant differences in Az values between the two groups. For the differentiation of solid, malignant hepatic lesions from nonsolid, benign hepatic lesions, there is no difference in accuracy between dual-echo T2-weighted TSE MR imaging and the additional use of

  9. Directed neuronal differentiation of human embryonic stem cells

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    Noggle Scott A

    2003-10-01

    Full Text Available Abstract Background We have developed a culture system for the efficient and directed differentiation of human embryonic stem cells (HESCs to neural precursors and neurons. HESC were maintained by manual passaging and were differentiated to a morphologically distinct OCT-4+/SSEA-4- monolayer cell type prior to the derivation of embryoid bodies. Embryoid bodies were grown in suspension in serum free conditions, in the presence of 50% conditioned medium from the human hepatocarcinoma cell line HepG2 (MedII. Results A neural precursor population was observed within HESC derived serum free embryoid bodies cultured in MedII conditioned medium, around 7–10 days after derivation. The neural precursors were organized into rosettes comprised of a central cavity surrounded by ring of cells, 4 to 8 cells in width. The central cells within rosettes were proliferating, as indicated by the presence of condensed mitotic chromosomes and by phosphoHistone H3 immunostaining. When plated and maintained in adherent culture, the rosettes of neural precursors were surrounded by large interwoven networks of neurites. Immunostaining demonstrated the expression of nestin in rosettes and associated non-neuronal cell types, and a radial expression of Map-2 in rosettes. Differentiated neurons expressed the markers Map-2 and Neurofilament H, and a subpopulation of the neurons expressed tyrosine hydroxylase, a marker for dopaminergic neurons. Conclusion This novel directed differentiation approach led to the efficient derivation of neuronal cultures from HESCs, including the differentiation of tyrosine hydroxylase expressing neurons. HESC were morphologically differentiated to a monolayer OCT-4+ cell type, which was used to derive embryoid bodies directly into serum free conditions. Exposure to the MedII conditioned medium enhanced the derivation of neural precursors, the first example of the effect of this conditioned medium on HESC.

  10. [Notch signaling pathway participates in the differentiation of hepatic progenitor cells into bile duct epithelial cells and progression of hepatic fibrosis in cholestatic liver fibrosis rat].

    Science.gov (United States)

    Mu, Y P; Zhang, X; Xu, Y; Fan, W W; Li, X W; Chen, J M; Chen, G F; Liu, P

    2017-06-08

    Objective: To investigate differentiation direction of hepatic progenitor cells (HPCs) in cholestatic liver fibrosis (CLF), and the role of Notch signaling pathway in the differentiation of HPCs. Methods: A CLF rat model was established by bile duct ligation (BDL) followed by monitoring changes of Notch signal pathway and the cellular origin of proliferating cholangiocytes. After intraperitoneal injection of DAPT (a Notch signaling inhibitor) after bile duct ligation, the progress of liver fibrosis and the proliferation of cholangiocytes after inhibition of the Notch pathway were analyzed. Results: Data showed that bile duct proliferation gradually increased along with inflammatory cell infiltration and proliferating bile duct cells surrounded by abundant collagen in the BDL group. Immunostaining confirmed markedly increased expression of CK19, OV6, Sox9 and EpCAM. In addition, RT-PCR results showed that Notch signaling pathway was activated significantly. Once the Notch signaling pathway was inhibited by DAPT, bile duct proliferation markedly suppressed along with significantly decreased the mRNA expression of CK19, OV6, Sox9 and EpCAM, compared with BDL group [(10.2±0.7) vs . (22.3±0.8), (7.6±1.5) vs . (18.1±3.7), (1.4±0.4) vs . (4.1±1.1), (1.3±0.3) vs . (5.0±1.4), respectively, P liver fibrosis was also reduced significantly. Conclusion: Notch signaling activation is required for HPCs differentiation into cholangiocytes in CLF and inhibition of the Notch signaling pathway may offer a therapeutic option for treating CLF.

  11. Differential Effects of Three Techniques for Hepatic Vascular Exclusion during Resection for Liver Cirrhosis on Hepatic Ischemia-Reperfusion Injury in Rats

    Directory of Open Access Journals (Sweden)

    Changjun Jia

    2018-01-01

    Full Text Available Background/Aims. Hepatic ischemia-reperfusion (I/R injury is a serious concern during hepatic vascular occlusion. The objectives of this study were to assess effects of three techniques for hepatic vascular occlusion on I/R injury and to explore the underlying mechanisms. Methods. Liver cirrhotic rats had undertaken Pringle maneuver (PR, hemihepatic vascular occlusion (HH, or hepatic blood inflow occlusion without hemihepatic artery control (WH. Levels of tumor necrosis factor alpha (TNF-α, nuclear factor kappa B (NF-κB, toll-like receptor 4 (TLR4, TIR-domain-containing adapter-inducing interferon-β (TRIF, and hemeoxygenase 1 (HMOX1 were assayed. Results. The histopathologic analysis displayed that liver harm was more prominent in the PR group, but similar in the HH and WH groups. The HH and WH groups responded to hepatic I/R inflammation similarly but better than the PR group. Mechanical studies suggested that TNF-α/NF-κB signaling and TLR4/TRIF transduction pathways were associated with the differential effects. In addition, the HH and WH groups had significantly higher levels of hepatic HMOX1 (P<0.05 than the PR group. Conclusions. HH and WH confer better preservation of liver function and protection than the Pringle maneuver in combating I/R injury. Upregulation of HMOX1 may lead to better protection and clinical outcomes after liver resection.

  12. Computed tomography of liver tumors, 2. Differential diagnosis between hepatocellular carcinoma and metastatic hepatic tumor by dynamic CT scanning

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    Naito, Akira; Fukuoka, Haruhito; Kashiwado, Kouzou; Ichiki, Toshio; Makidono, Yoko [Hiroshima Red Cross Hospital (Japan)

    1984-02-01

    Differential diagnosis between hepatocellular carcinoma and metastatic hepatic tumor was attempted using dynamic CT scanning. Homogeneous and patchy types were peculiar to hepatocellular carcinoma, and ring-like type to metastatic hepatic tumor. However, with no enhancement, hepatocellular carcinoma could not be denied. Hepatocellular carcinoma was characterized by the enhancement shown on the early stage of dynamic CT. Ring enhancement was not visualized on dynamic CT but visualized on conventional contrast enhanced CT in hepatocellular carcinomas; it was visualized on conventional contrast enhanced CT and on dynamic CT in metastatic hepatic tumors.

  13. Ethanol negatively regulates hepatic differentiation of hESC by inhibition of the MAPK/ERK signaling pathway in vitro.

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    Wei Gao

    Full Text Available Alcohol insult triggers complex events in the liver, promoting fibrogenic/inflammatory signals and in more advanced cases, aberrant matrix deposition. It is well accepted that the regenerative capacity of the adult liver is impaired during alcohol injury. The liver progenitor/stem cells have been shown to play an important role in liver regeneration -in response to various chronic injuries; however, the effects of alcohol on stem cell differentiation in the liver are not well understood.We employed hepatic progenitor cells derived from hESCs to study the impact of ethanol on hepatocyte differentiation by exposure of these progenitor cells to ethanol during hepatocyte differentiation.We found that ethanol negatively regulated hepatic differentiation of hESC-derived hepatic progenitor cells in a dose-dependent manner. There was also a moderate cell cycle arrest at G1/S checkpoint in the ethanol treated cells, which is associated with a reduced level of cyclin D1 in these cells. Ethanol treatment specifically inhibited the activation of the ERK but not JNK nor the p38 MAP signaling pathway. At the same time, the WNT signaling pathway was also reduced in the cells exposed to ethanol. Upon evaluating the effects of the inhibitors of these two signaling pathways, we determined that the Erk inhibitor replicated the effects of ethanol on the hepatocyte differentiation and attenuated the WNT/β-catenin signaling, however, inhibitors of WNT only partially replicated the effects of ethanol on the hepatocyte differentiation.Our results demonstrated that ethanol negatively regulated hepatic differentiation of hESC-derived hepatic progenitors through inhibiting the MAPK/ERK signaling pathway, and subsequently attenuating the WNT signaling pathway. Thus, our finding provides a novel insight into the mechanism by which alcohol regulates cell fate selection of hESC-derived hepatic progenitor cells, and the identified pathways may provide therapeutic targets

  14. Differential Binding Models for Direct and Reverse Isothermal Titration Calorimetry.

    Science.gov (United States)

    Herrera, Isaac; Winnik, Mitchell A

    2016-03-10

    Isothermal titration calorimetry (ITC) is a technique to measure the stoichiometry and thermodynamics from binding experiments. Identifying an appropriate mathematical model to evaluate titration curves of receptors with multiple sites is challenging, particularly when the stoichiometry or binding mechanism is not available. In a recent theoretical study, we presented a differential binding model (DBM) to study calorimetry titrations independently of the interaction among the binding sites (Herrera, I.; Winnik, M. A. J. Phys. Chem. B 2013, 117, 8659-8672). Here, we build upon our DBM and show its practical application to evaluate calorimetry titrations of receptors with multiple sites independently of the titration direction. Specifically, we present a set of ordinary differential equations (ODEs) with the general form d[S]/dV that can be integrated numerically to calculate the equilibrium concentrations of free and bound species S at every injection step and, subsequently, to evaluate the volume-normalized heat signal (δQ(V) = δq/dV) of direct and reverse calorimetry titrations. Additionally, we identify factors that influence the shape of the titration curve and can be used to optimize the initial concentrations of titrant and analyte. We demonstrate the flexibility of our updated DBM by applying these differentials and a global regression analysis to direct and reverse calorimetric titrations of gadolinium ions with multidentate ligands of increasing denticity, namely, diglycolic acid (DGA), citric acid (CIT), and nitrilotriacetic acid (NTA), and use statistical tests to validate the stoichiometries for the metal-ligand pairs studied.

  15. Direct economic burden of hepatitis B virus related diseases: evidence from Shandong, China.

    Science.gov (United States)

    Lu, Jingjing; Xu, Aiqiang; Wang, Jian; Zhang, Li; Song, Lizhi; Li, Renpeng; Zhang, Shunxiang; Zhuang, Guihua; Lu, Mingshan

    2013-01-31

    Although the expenses of liver cirrhosis are covered by a critical illness fund under the current health insurance program in China, the economic burden associated with hepatitis B virus (HBV) related diseases is not well addressed. In order to provide evidence to address the economic disease burden of HBV, we conducted a survey to investigate the direct economic burden of acute and chronic hepatitis B, cirrhosis and liver cancer caused by HBV-related disease. From April 2010 to November 2010, we conducted a survey of inpatients with HBV-related diseases and who were hospitalized for seven or more days in one of the seven tertiary and six secondary hospitals in Shandong, China. Patients were recorded consecutively within a three-to-five month time period from each sampled hospital; an in-person survey was conducted to collect demographic and socio-economic information, as well as direct medical and nonmedical expenses during the last month and last year prior to the current hospitalization. Direct medical costs included total outpatient, inpatient, and self-treatment expenditures; direct nonmedical costs included spending on nutritional supplements, transportation, and nursing. Direct medical costs during the current hospitalization were also obtained from the hospital financial database. The direct economic cost was calculated as the sum of direct medical and nonmedical costs. Our results call for the importance of implementing clinical guideline, improving system accountability, and helping secondary and smaller hospitals to improve efficiency. This has important policy implication for the on-going hospital reform in China. Our data based on inpatients with HBV-related diseases suggested that the direct cost in US dollars for acute hepatitis B, severe hepatitis B, chronic hepatitis B, compensated cirrhosis, decompensated cirrhosis and primary liver cancer was $2954, $10834, $4552, $7400.28, $6936 and $10635, respectively. These costs ranged from 30.72% (for acute

  16. Direct economic burden of hepatitis B virus related diseases: evidence from Shandong, China

    Directory of Open Access Journals (Sweden)

    Lu Jingjing

    2013-01-01

    Full Text Available Abstract Background Although the expenses of liver cirrhosis are covered by a critical illness fund under the current health insurance program in China, the economic burden associated with hepatitis B virus (HBV related diseases is not well addressed. In order to provide evidence to address the economic disease burden of HBV, we conducted a survey to investigate the direct economic burden of acute and chronic hepatitis B, cirrhosis and liver cancer caused by HBV-related disease. Methods From April 2010 to November 2010, we conducted a survey of inpatients with HBV-related diseases and who were hospitalized for seven or more days in one of the seven tertiary and six secondary hospitals in Shandong, China. Patients were recorded consecutively within a three-to-five month time period from each sampled hospital; an in-person survey was conducted to collect demographic and socio-economic information, as well as direct medical and nonmedical expenses during the last month and last year prior to the current hospitalization. Direct medical costs included total outpatient, inpatient, and self-treatment expenditures; direct nonmedical costs included spending on nutritional supplements, transportation, and nursing. Direct medical costs during the current hospitalization were also obtained from the hospital financial database. The direct economic cost was calculated as the sum of direct medical and nonmedical costs. Our results call for the importance of implementing clinical guideline, improving system accountability, and helping secondary and smaller hospitals to improve efficiency. This has important policy implication for the on-going hospital reform in China. Results Our data based on inpatients with HBV-related diseases suggested that the direct cost in US dollars for acute hepatitis B, severe hepatitis B, chronic hepatitis B, compensated cirrhosis, decompensated cirrhosis and primary liver cancer was $2954, $10834, $4552, $7400.28, $6936 and $10635

  17. Differential effects of arsenic trioxide on chemosensitization in human hepatic tumor and stellate cell lines

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    Rangwala Fatima

    2012-09-01

    Full Text Available Abstract Background Crosstalk between malignant hepatocytes and the surrounding peritumoral stroma is a key modulator of hepatocarcinogenesis and therapeutic resistance. To examine the chemotherapy resistance of these two cellular compartments in vitro, we evaluated a well-established hepatic tumor cell line, HepG2, and an adult hepatic stellate cell line, LX2. The aim was to compare the chemosensitization potential of arsenic trioxide (ATO in combination with sorafenib or fluorouracil (5-FU, in both hepatic tumor cells and stromal cells. Methods Cytotoxicity of ATO, 5-FU, and sorafenib, alone and in combination against HepG2 cells and LX2 cells was measured by an automated high throughput cell-based proliferation assay. Changes in survival and apoptotic signaling pathways were analyzed by flow cytometry and western blot. Gene expression of the 5-FU metabolic enzyme, thymidylate synthase, was analyzed by real time PCR. Results Both HepG2 and LX2 cell lines were susceptible to single agent sorafenib and ATO at 24 hr (ATO IC50: 5.3 μM in LX2; 32.7 μM in HepG2; Sorafenib IC50: 11.8 μM in LX2; 9.9 μM in HepG2. In contrast, 5-FU cytotoxicity required higher concentrations and prolonged (48–72 hr drug exposure. Concurrent ATO and 5-FU treatment of HepG2 cells was synergistic, leading to increased cytotoxicity due in part to modulation of thymidylate synthase levels by ATO. Concurrent ATO and sorafenib treatment showed a trend towards increased HepG2 cytotoxicity, possibly due to a significant decrease in MAPK activation in comparison to treatment with ATO alone. Conclusions ATO differentially sensitizes hepatic tumor cells and adult hepatic stellate cells to 5-FU and sorafenib. Given the importance of both of these cell types in hepatocarcinogenesis, these data have implications for the rational development of anti-cancer therapy combinations for the treatment of hepatocellular carcinoma (HCC.

  18. Differential effects of arsenic trioxide on chemosensitization in human hepatic tumor and stellate cell lines

    International Nuclear Information System (INIS)

    Rangwala, Fatima; Williams, Kevin P; Smith, Ginger R; Thomas, Zainab; Allensworth, Jennifer L; Lyerly, H Kim; Diehl, Anna Mae; Morse, Michael A; Devi, Gayathri R

    2012-01-01

    Crosstalk between malignant hepatocytes and the surrounding peritumoral stroma is a key modulator of hepatocarcinogenesis and therapeutic resistance. To examine the chemotherapy resistance of these two cellular compartments in vitro, we evaluated a well-established hepatic tumor cell line, HepG2, and an adult hepatic stellate cell line, LX2. The aim was to compare the chemosensitization potential of arsenic trioxide (ATO) in combination with sorafenib or fluorouracil (5-FU), in both hepatic tumor cells and stromal cells. Cytotoxicity of ATO, 5-FU, and sorafenib, alone and in combination against HepG2 cells and LX2 cells was measured by an automated high throughput cell-based proliferation assay. Changes in survival and apoptotic signaling pathways were analyzed by flow cytometry and western blot. Gene expression of the 5-FU metabolic enzyme, thymidylate synthase, was analyzed by real time PCR. Both HepG2 and LX2 cell lines were susceptible to single agent sorafenib and ATO at 24 hr (ATO IC 50 : 5.3 μM in LX2; 32.7 μM in HepG2; Sorafenib IC 50 : 11.8 μM in LX2; 9.9 μM in HepG2). In contrast, 5-FU cytotoxicity required higher concentrations and prolonged (48–72 hr) drug exposure. Concurrent ATO and 5-FU treatment of HepG2 cells was synergistic, leading to increased cytotoxicity due in part to modulation of thymidylate synthase levels by ATO. Concurrent ATO and sorafenib treatment showed a trend towards increased HepG2 cytotoxicity, possibly due to a significant decrease in MAPK activation in comparison to treatment with ATO alone. ATO differentially sensitizes hepatic tumor cells and adult hepatic stellate cells to 5-FU and sorafenib. Given the importance of both of these cell types in hepatocarcinogenesis, these data have implications for the rational development of anti-cancer therapy combinations for the treatment of hepatocellular carcinoma (HCC)

  19. FLAIR-HASTE sequence in differential diagnosis of focal hepatic lesions

    International Nuclear Information System (INIS)

    Kim, Yong Jae; Kim, Tae Kyoung; Bae, In Young; Kim, Pyo Nyun; Ha, Hyun Kwon; Kim, Ah Young; Lee, Moon Gyu

    2001-01-01

    To assess the feasibility of using the FLAIR (fluid-attenuated inversion recovery)-HASTE (half-fourier acquisition single-shot turbo spin-echo) sequence for the differential diagnosis of focal hepatic lesions. During a 12-month period, 80 patients with 127 focal hepatic lesions [hemangiomas (n=60), hepatocellular carcinomas (HCC) (n=27), cysts (n=25), and metastases (n=15) underwent MR imaging using a 1.5-T scanner. Verification of the diagnosis was based on the findings of pathology (n=11), of angiography and clinical investigation (n=17), or of dynamic contrast-enhanced MR imaging (n=99). MR sequences included T2-weighted HASTE (TE, 134 ms ; echo space, 4.4 ms), FLAIR-HASTE (TE, 64 ms ; echo space, 4.4 ms ; inversion time, 2000 ms ; number of slices, 5-9 ; acquisition time, 13-20 s), and dynamic gadolinium-enhanced T1-weighted FLASH (TR, 131 ms ; TE, 4 ms). FLAIR-HASTE imaging was of any focal lesions seen on T2-weighted HASTE images was performed in the liver area, and their signal intensity was classified in one of five ways : very high (higher than the spleen), moderately high (similar to the spleen), slightly high (higher than the liver and lower than the spleen), intermediate (similar to the liver), or low (lower than the liver). The signal intensity of the 25 cysts, as determined by FLAIR-HASTE, was low in 21 cases (84%), intermediate in three (12%), and very high in one (4%), which was diagnosed as a complicated cyst in which ultrasound revealed internal septa. At FLAIR-HASTE, all 60 hemangiomas showed either very high (n=50, 83%) or moderately high (n=10, 17%) signal intensity, while that of 42 hepatic malignant tumors was very high in 14 cases (33%), moderately high in 8 (19%), slightly high in 18 (43%), intermediate in one (2.5%), and low in one (2.5%). FLAIR-HASTE showed that the signal intensity of the majority of hepatic cysts was low, while that of most hemangiomas and solid liver tumors was high. For the differential diagnosis of cystic and

  20. Spectral CT imaging in the differential diagnosis of necrotic hepatocellular carcinoma and hepatic abscess

    International Nuclear Information System (INIS)

    Yu, Y.; Guo, L.; Hu, C.; Chen, K.

    2014-01-01

    Aim: To explore the value of CT spectral imaging in the differential diagnosis of necrotic hepatocellular carcinoma (nHCC) and hepatic abscess (HA) during the arterial phase (AP) and portal venous phase (PP). Materials and methods: Sixty patients with 36 nHCCs and 24 HAs underwent spectral CT during AP and PP. Iodine or water concentration were measured and the normalized iodine concentration (NIC) and lesion-normal parenchyma iodine concentration ratio (LNR) were calculated. The two-sample t-test was used to compare quantitative parameters. Two readers qualitatively assessed lesion types according to imaging features. Sensitivity and specificity were compared between the qualitative and quantitative studies. Results: NIC and LNR in the AP for the wall of nHCC (0.14 ± 0.04 mg/ml; 2.77 ± 0.74) were higher than those of HA (0.13 ± 0.02 mg/ml; 1.4 ± 0.9). NIC and LNR in the PP for the wall of HA (0.66 ± 0.05 mg/ml; 1.2 ± 0.2) were higher than those of nHCC (0.5 ± 0.11 mg/ml; 0.94 ± 0.12). The differences in NIC in the AP were not significant but the differences in LNR in AP, and NIC and LNR in the PP were significant. The best quantitative parameter was LNR in AP, and a threshold of 1.52 would yield a sensitivity and specificity of 100% and 91.7%, respectively, for differentiating nHCC from HA. Conclusion: CT spectral imaging with quantitative iodine concentration analysis may help to increase the accuracy of differentiating nHCC from HA. - Highlights: • We preliminarily investigate the usefulness of CT spectral imaging in differentiating nHCC from HA. • CT spectral imaging may help differentiate necrotic hepatocellular carcinoma from hepatic abscess. • CT spectral imaging can evaluate the blood supply and necrotic degree of lesions. • Quantitative analysis of iodine concentration provides greater diagnostic confidence

  1. Engineering kidney cells: reprogramming and directed differentiation to renal tissues.

    Science.gov (United States)

    Kaminski, Michael M; Tosic, Jelena; Pichler, Roman; Arnold, Sebastian J; Lienkamp, Soeren S

    2017-07-01

    Growing knowledge of how cell identity is determined at the molecular level has enabled the generation of diverse tissue types, including renal cells from pluripotent or somatic cells. Recently, several in vitro protocols involving either directed differentiation or transcription-factor-based reprogramming to kidney cells have been established. Embryonic stem cells or induced pluripotent stem cells can be guided towards a kidney fate by exposing them to combinations of growth factors or small molecules. Here, renal development is recapitulated in vitro resulting in kidney cells or organoids that show striking similarities to mammalian embryonic nephrons. In addition, culture conditions are also defined that allow the expansion of renal progenitor cells in vitro. Another route towards the generation of kidney cells is direct reprogramming. Key transcription factors are used to directly impose renal cell identity on somatic cells, thus circumventing the pluripotent stage. This complementary approach to stem-cell-based differentiation has been demonstrated to generate renal tubule cells and nephron progenitors. In-vitro-generated renal cells offer new opportunities for modelling inherited and acquired renal diseases on a patient-specific genetic background. These cells represent a potential source for developing novel models for kidney diseases, drug screening and nephrotoxicity testing and might represent the first steps towards kidney cell replacement therapies. In this review, we summarize current approaches for the generation of renal cells in vitro and discuss the advantages of each approach and their potential applications.

  2. Intravoxel Incoherent Motion Diffusion-weighted Imaging: Evaluation of the Differentiation of Solid Hepatic Lesions

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    Ma Luo

    2017-10-01

    Full Text Available PURPOSE: To evaluate whether intravoxel incoherent motion (IVIM–related parameters could be used to differentiate malignant from benign focal liver lesions (FLLs and to improve diagnostic efficiency. METHODS: Seventy-four patients with 75 lesions, including 51 malignant FLLs and 24 benign FLLs, underwent liver 3.0-T magnetic resonance imaging for routine examination sequences. IVIM diffusion-weighted imaging (DWI with 11 b values (0-800 s/mm2 was also acquired concurrently. Apparent diffusion coefficient (ADCtotal and IVIM-derived parameters, such as the pure diffusion coefficient (D, the pseudodiffusion coefficient (D⁎, and the perfusion fraction (f, were calculated and compared between the two groups. A receiver operating characteristic curve analysis was performed to assess their diagnostic value. RESULTS: ADCtotal, D, and f were significantly lower in the malignant group than in the benign group, whereas D⁎ did not show a statistical difference. D had a larger area under the curve value (0.968 and higher sensitivity (92.30% for differentiation. CONCLUSION: IVIM is a useful method to differentiate malignant and benign FLLs. The D value showed higher efficacy to detect hepatic solid lesions.

  3. Human dental pulp stem cells derived from cryopreserved dental pulp tissues of vital extracted teeth with disease demonstrate hepatic-like differentiation.

    Science.gov (United States)

    Chen, Y K; Huang, Anderson H C; Chan, Anthony W S; Lin, L M

    2016-06-01

    Reviewing the literature, hepatic differentiation of human dental pulp stem cells (hDPSCs) from cryopreserved dental pulp tissues of vital extracted teeth with disease has not been studied. This study is aimed to evaluate the hypothesis that hDPSCs from cryopreserved dental pulp tissues of vital extracted teeth with disease could possess potential hepatic differentiation. Forty vital extracted teeth with disease recruited for hDPSCs isolation, stem cell characterization and hepatic differentiation were randomly and equally divided into group A (liquid nitrogen-stored dental pulp tissues) and group B (freshly derived dental pulp tissues). Samples of hDPSCs isolated from groups A and B but without hepatic growth factors formed negative controls. A well-differentiated hepatocellular carcinoma cell line was employed as a positive control. All the isolated hDPSCs from groups A and B showed hepatic-like differentiation with morphological change from a spindle-shaped to a polygonal shape and normal karyotype. Differentiated hDPSCs and the positive control expressed hepatic metabolic function genes and liver-specific genes. Glycogen storage of differentiated hDPSCs was noted from day 7 of differentiation-medium culture. Positive immunofluorescence staining of low-density lipoprotein and albumin was observed from day 14 of differentiation-medium culture; urea production in the medium was noted from week 6. No hepatic differentiation was observed for any of the samples of the negative controls. We not only demonstrated the feasibility of hepatic-like differentiation of hDPSCs from cryopreserved dental pulp tissues of vital extracted teeth with disease but also indicated that the differentiated cells possessed normal karyotype and were functionally close to normal hepatic-like cells. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  4. Dynamics of a delay differential equation model of hepatitis B virus infection.

    Science.gov (United States)

    Gourley, Stephen A; Kuang, Yang; Nagy, John D

    2008-04-01

    We formulate and systematically study the global dynamics of a simple model of hepatitis B virus in terms of delay differential equations. This model has two important and novel features compared to the well-known basic virus model in the literature. Specifically, it makes use of the more realistic standard incidence function and explicitly incorporates a time delay in virus production. As a result, the infection reproduction number is no longer dependent on the patient liver size (number of initial healthy liver cells). For this model, the existence and the component values of the endemic steady state are explicitly dependent on the time delay. In certain biologically interesting limiting scenarios, a globally attractive endemic equilibrium can exist regardless of the time delay length.

  5. Management of hepatitis C infection in the era of direct-acting antiviral therapy

    Science.gov (United States)

    Zain, L. H.; Sungkar, T.

    2018-03-01

    Hepatitis C viral infection globally affects millions of people and commonly results in debilitating complications and mortality. Initial mainstay therapy consisted of pegylated interferon α (pegIFNα) with additional ribavirin that showed unsatisfactory cure rate, common side effects and complicated dosing, contributing to high discontinuation rate. Over the last few years, newer antivirals have been extensively studied, that are Direct-Acting Antivirals (DAAs). Specifically targeting viral protein mainly during replication phase, DAAs showed greater cure rate (commonly measured as sustained virologic response), improved safety profile and shorter treatment duration compared to traditional interferon-ribavirin therapy. Current guidelines have also included Interferon-free, often ribavirin-free, DAAs combinations that suggest promising outcomes. The current review highlights development of rapidly growing hepatitis C treatment including DAAs recommendations.

  6. Segmentation of hepatic artery in multi-phase liver CT using directional dilation and connectivity analysis

    Science.gov (United States)

    Wang, Lei; Schnurr, Alena-Kathrin; Zidowitz, Stephan; Georgii, Joachim; Zhao, Yue; Razavi, Mohammad; Schwier, Michael; Hahn, Horst K.; Hansen, Christian

    2016-03-01

    Segmentation of hepatic arteries in multi-phase computed tomography (CT) images is indispensable in liver surgery planning. During image acquisition, the hepatic artery is enhanced by the injection of contrast agent. The enhanced signals are often not stably acquired due to non-optimal contrast timing. Other vascular structure, such as hepatic vein or portal vein, can be enhanced as well in the arterial phase, which can adversely affect the segmentation results. Furthermore, the arteries might suffer from partial volume effects due to their small diameter. To overcome these difficulties, we propose a framework for robust hepatic artery segmentation requiring a minimal amount of user interaction. First, an efficient multi-scale Hessian-based vesselness filter is applied on the artery phase CT image, aiming to enhance vessel structures with specified diameter range. Second, the vesselness response is processed using a Bayesian classifier to identify the most probable vessel structures. Considering the vesselness filter normally performs not ideally on the vessel bifurcations or the segments corrupted by noise, two vessel-reconnection techniques are proposed. The first technique uses a directional morphological operator to dilate vessel segments along their centerline directions, attempting to fill the gap between broken vascular segments. The second technique analyzes the connectivity of vessel segments and reconnects disconnected segments and branches. Finally, a 3D vessel tree is reconstructed. The algorithm has been evaluated using 18 CT images of the liver. To quantitatively measure the similarities between segmented and reference vessel trees, the skeleton coverage and mean symmetric distance are calculated to quantify the agreement between reference and segmented vessel skeletons, resulting in an average of 0:55+/-0:27 and 12:7+/-7:9 mm (mean standard deviation), respectively.

  7. In vitro proliferation and differentiation of hepatic oval cells and their potential capacity for intrahepatic transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Z.; Chen, J. [Liaocheng People' s Hospital, Department of Hepatobiliary Surgery, Liaocheng, Shandong, China, Department of Hepatobiliary Surgery, Liaocheng People’s Hospital, Liaocheng, Shandong (China); Li, L.; Ran, J.H.; Liu, J. [The First People' s Hospital of Kunming, Kunming, Yunnan, China, The First People’s Hospital of Kunming, Kunming, Yunnan (China); Gao, T.X.; Guo, B.Y. [Dongchangfu Hospital of Women and Child Health Care, Liaocheng, Shandong (China); Li, X.H.; Liu, Z.H.; Liu, G.J.; Gao, Y.C.; Zhang, X.L. [Liaocheng People' s Hospital, Department of Hepatobiliary Surgery, Liaocheng, Shandong, China, Department of Hepatobiliary Surgery, Liaocheng People’s Hospital, Liaocheng, Shandong (China)

    2013-07-30

    Hepatic oval cells (HOCs) are recognized as facultative liver progenitor cells that play a role in liver regeneration after acute liver injury. Here, we investigated the in vitro proliferation and differentiation characteristics of HOCs in order to explore their potential capacity for intrahepatic transplantation. Clusters or scattered HOCs were detected in the portal area and interlobular bile duct in the liver of rats subjected to the modified 2-acetylaminofluorene and partial hepatectomy method. Isolated HOCs were positive for c-kit and CD90 staining (99.8% and 88.8%, respectively), and negative for CD34 staining (3.6%) as shown by immunostaining and flow cytometric analysis. In addition, HOCs could be differentiated into hepatocytes and bile duct epithelial cells after leukemia inhibitory factor deprivation. A two-cuff technique was used for orthotopic liver transplantation, and HOCs were subsequently transplanted into recipients. Biochemical indicators of liver function were assessed 4 weeks after transplantation. HOC transplantation significantly prolonged the median survival time and improved the liver function of rats receiving HOCs compared to controls (P=0.003, Student t-test). Administration of HOCs to rats also receiving liver transplantation significantly reduced acute allograft rejection compared to control liver transplant rats 3 weeks following transplantation (rejection activity index score: control=6.3±0.9; HOC=3.5±1.5; P=0.005). These results indicate that HOCs may be useful in therapeutic liver regeneration after orthotopic liver transplantation.

  8. In vitro proliferation and differentiation of hepatic oval cells and their potential capacity for intrahepatic transplantation

    International Nuclear Information System (INIS)

    Li, Z.; Chen, J.; Li, L.; Ran, J.H.; Liu, J.; Gao, T.X.; Guo, B.Y.; Li, X.H.; Liu, Z.H.; Liu, G.J.; Gao, Y.C.; Zhang, X.L.

    2013-01-01

    Hepatic oval cells (HOCs) are recognized as facultative liver progenitor cells that play a role in liver regeneration after acute liver injury. Here, we investigated the in vitro proliferation and differentiation characteristics of HOCs in order to explore their potential capacity for intrahepatic transplantation. Clusters or scattered HOCs were detected in the portal area and interlobular bile duct in the liver of rats subjected to the modified 2-acetylaminofluorene and partial hepatectomy method. Isolated HOCs were positive for c-kit and CD90 staining (99.8% and 88.8%, respectively), and negative for CD34 staining (3.6%) as shown by immunostaining and flow cytometric analysis. In addition, HOCs could be differentiated into hepatocytes and bile duct epithelial cells after leukemia inhibitory factor deprivation. A two-cuff technique was used for orthotopic liver transplantation, and HOCs were subsequently transplanted into recipients. Biochemical indicators of liver function were assessed 4 weeks after transplantation. HOC transplantation significantly prolonged the median survival time and improved the liver function of rats receiving HOCs compared to controls (P=0.003, Student t-test). Administration of HOCs to rats also receiving liver transplantation significantly reduced acute allograft rejection compared to control liver transplant rats 3 weeks following transplantation (rejection activity index score: control=6.3±0.9; HOC=3.5±1.5; P=0.005). These results indicate that HOCs may be useful in therapeutic liver regeneration after orthotopic liver transplantation

  9. A study on an automated computerized differential diagnosis of diffuse liver diseases, based only on hepatic scintigrams using sup(99m)Tc-Sn-colloid

    International Nuclear Information System (INIS)

    Matsuo, Michimasa; Fujii, Susumu; Kaneda, Yukio

    1980-01-01

    Hepatic scintigrams using sup(99m)Tc-compounds are now routinely performed. In this study, automated computerized pattern characterizations of right lateral hepatic scintigrams using sup(99m)Tc-Sn colloid were studied to extract characteristic indicators, which are effective for an automated computerized differential diagnosis. The program, developed by us, of the automated computerized pattern characterization and the automated computerized differential diagnosis can be performed without the aid of professional doctors' ability of pattern recognition. The right lateral hepatic scintigrams of fifty one cases, which are accurately diagnosed by biopsy, are applied as the training group. The results of the automated computerized differential diagnosis were as follows: Three cases were accurately diagnosed among 3 normal cases; Three among 3 acute hepatitis; Seven among 7 chronic inactive hepatitis; Twenty among 22 chronic active hepatitis; Sixteen among 16 liver cirrhosis. Only two cases of chronic active hepatitis are falsely-diagnosed as chronic inactive hepatitis and as liver cirrhosis respectively. The over all accuracy rate was 96% in the training group. With this result, the automated computerized differential diagnosis of diffuse liver diseases is suggested to be possible, based on the hepatic scintigram. (author)

  10. Pharmacogenetics of hepatitis C: transition from interferon-based therapies to direct-acting antiviral agents

    Directory of Open Access Journals (Sweden)

    Kamal SM

    2014-06-01

    Full Text Available Sanaa M Kamal1,21Department of Medicine, Division of Hepatology, Gastroenterology and Tropical Medicine, Ain Shams Faculty of Medicine, Cairo, Egypt, 2Department of Medicine, Salman Bin Abdul Aziz College of Medicine, Kingdom of Saudi ArabiaAbstract: Hepatitis C virus (HCV has emerged as a major viral pandemic over the past two decades, infecting 170 million individuals, which equates to approximately 3% of the world's population. The prevalence of HCV varies according to geographic region, being highest in developing countries such as Egypt. HCV has a high tendency to induce chronic progressive liver damage in the form of hepatic fibrosis, cirrhosis, or liver cancer. To date, there is no vaccine against HCV infection. Combination therapy comprising PEGylated interferon-alpha and ribavirin has been the standard of care for patients with chronic hepatitis C for more than a decade. However, many patients still do not respond to therapy or develop adverse events. Recently, direct antiviral agents such as protease inhibitors, polymerase inhibitors, or NS5A inhibitors have been used to augment PEGylated interferon and ribavirin, resulting in better efficacy, better tolerance, and a shorter treatment duration. However, most clinical trials have focused on assessing the efficacy and safety of direct antiviral agents in patients with genotype 1, and the response of other HCV genotypes has not been elucidated. Moreover, the prohibitive costs of such triple therapies will limit their use in patients in developing countries where most of the HCV infection exists. Understanding the host and viral factors associated with viral clearance is necessary for individualizing therapy to maximize sustained virologic response rates, prevent progression to liver disease, and increase the overall benefits of therapy with respect to its costs. Genome wide studies have shown significant associations between a set of polymorphisms in the region of the interleukin-28B (IL

  11. Directed technical change and differentiation of climate policy

    International Nuclear Information System (INIS)

    Otto, Vincent M.; Loeschel, Andreas; Reilly, John

    2008-01-01

    This paper studies the cost effectiveness of climate policy if there are technology externalities. For this purpose, we develop a forward looking model that captures empirical links between CO 2 emissions associated with energy use, directed technical change and the economy. We find our most cost effective climate policy to include a combination of R and D subsidies and CO 2 emission constraints, although R and D subsidies raise the shadow value of the CO 2 constraint (i.e. CO 2 price) because of a strong rebound effect from stimulating innovation. Furthermore, we find that cost effectiveness of climate policy improves if it is differentiated between technologies. Even our rudimentary distinction between CO 2 intensive technologies and non-CO 2 intensive technologies lead to this result. Such differentiated climate policy encourages growth in the non-CO 2 intensive sectors and discourages growth in CO 2 intensive sectors by harnessing positive effects of technology externalities on total factor productivity in the former and letting the latter bear relatively more of the abatement burden. This result is robust to whether emission constraints, R and D subsidies or combinations of both are used as climate policy instruments. (author)

  12. Direct vs. indirect pathway of hepatic glycogen synthesis as a function of glucose infusion rate

    International Nuclear Information System (INIS)

    Bagby, G.J.; Lang, C.H.; Johnson, J.L.; Blakesly, H.L.; Spitzer, J.J.

    1986-01-01

    This study was initiated to determine the influence of the rate of exogenous glucose administration on liver glycogen synthesis by the direct (glucose uptake and incorporation into glycogen) vs the indirect pathway (glucose degradation to 3-carbon intermediates, e.g., lactate, prior to incorporation into glycogen). Catheterized rats were fasted 2 days prior to receiving a 3 hr infusion of glucose at rates of 0 to 230 μmol/min/kg containing tracer [6- 3 H]- and [U- 14 C]-glucose. Plasma glucose (r = 0.80), insulin (r = 0.90) and lactate (r = 0.84) were correlated with glucose infusion rate. The rate of liver glycogen deposition (0.46 +/- 0.03 μmol/min/g) did not differ between a glucose infusion rate of 20 and 230 μmol/min/kg. At the lowest and highest glucose infusion rates hepatic glycogenesis accounted for 87 +/- 6 and 9 +/- 1% of the total glucose load, respectively. The percent contribution of the direct pathways to glycogen deposition ([ 3 H] specific activity in hepatic glycogen/[ 3 H] specific activity in plasma glucose) increased from 16 +/- 3 to 83 +/- 5% from lowest to highest glucose infusion rates (prevailing plasma glucose concentrations: 9 +/- 1 and 21 +/- 2 mM, respectively). The results indicate that the relative contribution of the direct and indirect pathways of glucogen synthesis are dependent upon the glucose load or plasma glucose concentration

  13. Genetic Correction and Hepatic Differentiation of Hemophilia B-specific Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    He, Qiong; Wang, Hui-Hui; Cheng, Tao; Yuan, Wei-Ping; Ma, Yu-Po; Jiang, Yong-Ping; Ren, Zhi-Hua

    2017-09-27

    Objective To genetically correct a disease-causing point mutation in human induced pluripotent stem cells (iPSCs) derived from a hemophilia B patient. Methods First, the disease-causing mutation was detected by sequencing the encoding area of human coagulation factor IX (F IX) gene. Genomic DNA was extracted from the iPSCs, and the primers were designed to amplify the eight exons of F IX. Next, the point mutation in those iPSCs was genetically corrected using CRISPR/Cas9 technology in the presence of a 129-nucleotide homologous repair template that contained two synonymous mutations. Then, top 8 potential off-target sites were subsequently analyzed using Sanger sequencing. Finally, the corrected clones were differentiated into hepatocyte-like cells, and the secretion of F IX was validated by immunocytochemistry and ELISA assay. Results The cell line bore a missense mutation in the 6 th coding exon (c.676 C>T) of F IX gene. Correction of the point mutation was achieved via CRISPR/Cas9 technology in situ with a high efficacy at about 22% (10/45) and no off-target effects detected in the corrected iPSC clones. F IX secretion, which was further visualized by immunocytochemistry and quantified by ELISA in vitro, reached about 6 ng/ml on day 21 of differentiation procedure. Conclusions Mutations in human disease-specific iPSCs could be precisely corrected by CRISPR/Cas9 technology, and corrected cells still maintained hepatic differentiation capability. Our findings might throw a light on iPSC-based personalized therapies in the clinical application, especially for hemophilia B.

  14. Effects of Co-Culture Media on Hepatic Differentiation of hiPSC with or without HUVEC Co-Culture.

    Science.gov (United States)

    Freyer, Nora; Greuel, Selina; Knöspel, Fanny; Strahl, Nadja; Amini, Leila; Jacobs, Frank; Monshouwer, Mario; Zeilinger, Katrin

    2017-08-07

    The derivation of hepatocytes from human induced pluripotent stem cells (hiPSC) is of great interest for applications in pharmacological research. However, full maturation of hiPSC-derived hepatocytes has not yet been achieved in vitro. To improve hepatic differentiation, co-cultivation of hiPSC with human umbilical vein endothelial cells (HUVEC) during hepatic differentiation was investigated in this study. In the first step, different culture media variations based on hepatocyte culture medium (HCM) were tested in HUVEC mono-cultures to establish a suitable culture medium for co-culture experiments. Based on the results, two media variants were selected to differentiate hiPSC-derived definitive endodermal (DE) cells into mature hepatocytes with or without HUVEC addition. DE cells differentiated in mono-cultures in the presence of those media variants showed a significant increase ( p < 0.05) in secretion of α-fetoprotein and in activities of cytochrome P450 (CYP) isoenzymes CYP2B6 and CYP3A4 as compared with cells differentiated in unmodified HCM used as control. Co-cultivation with HUVEC did not further improve the differentiation outcome. Thus, it can be concluded that the effect of the used medium outweighed the effect of HUVEC co-culture, emphasizing the importance of the culture medium composition for hiPSC differentiation.

  15. Integration-deficient lentivectors: an effective strategy to purify and differentiate human embryonic stem cell-derived hepatic progenitors.

    Science.gov (United States)

    Yang, Guanghua; Si-Tayeb, Karim; Corbineau, Sébastien; Vernet, Rémi; Gayon, Régis; Dianat, Noushin; Martinet, Clémence; Clay, Denis; Goulinet-Mainot, Sylvie; Tachdjian, Gérard; Tachdjian, Gérard; Burks, Deborah; Vallier, Ludovic; Bouillé, Pascale; Dubart-Kupperschmitt, Anne; Weber, Anne

    2013-07-19

    Human pluripotent stem cells (hPSCs) hold great promise for applications in regenerative medicine. However, the safety of cell therapy using differentiated hPSC derivatives must be improved through methods that will permit the transplantation of homogenous populations of a specific cell type. To date, purification of progenitors and mature cells generated from either embryonic or induced pluripotent stem cells remains challenging with use of conventional methods. We used lentivectors encoding green fluorescent protein (GFP) driven by the liver-specific apoliprotein A-II (APOA-II) promoter to purify human hepatic progenitors. We evaluated both integrating and integration-defective lentivectors in combination with an HIV integrase inhibitor. A human embryonic stem cell line was differentiated into hepatic progenitors using a chemically defined protocol. Subsequently, cells were transduced and sorted at day 16 of differentiation to obtain a cell population enriched in hepatic progenitor cells. After sorting, more than 99% of these APOA-II-GFP-positive cells expressed hepatoblast markers such as α-fetoprotein and cytokeratin 19. When further cultured for 16 days, these cells underwent differentiation into more mature cells and exhibited hepatocyte properties such as albumin secretion. Moreover, they were devoid of vector DNA integration. We have developed an effective strategy to purify human hepatic cells from cultures of differentiating hPSCs, producing a novel tool that could be used not only for cell therapy but also for in vitro applications such as drug screening. The present strategy should also be suitable for the purification of a broad range of cell types derived from either pluripotent or adult stem cells.

  16. The value of gadoxetic acid-enhanced MRI for differentiation between hepatic microabscesses and metastases in patients with periampullary cancer

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seo-Youn [Soonchunhyang University College of Medicine, Bucheon Hospital, Department of Radiology, Bucheon (Korea, Republic of); Kim, Young Kon; Cha, Dong Ik; Jeong, Woo Kyoung; Lee, Won Jae [Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Seoul (Korea, Republic of); Min, Ji Hye [Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Seoul (Korea, Republic of); Chungnam National University Hospital, Chungnam National University College of Medicine, Department of Radiology, Daejeon (Korea, Republic of)

    2017-10-15

    We aimed to identify features that differentiate hepatic microabscess from hepatic metastasis on gadoxetic acid-enhanced MRI in patients with periampullary cancer. We included 72 patients (31 patients with 83 hepatic microabscesses and 41 patients with 71 hepatic metastases) who had a history of periampullary cancer and underwent gadoxetic acid-enhanced MRI. Image analysis was performed for margin, signal intensity, rim enhancement, perilesional hyperaemia, pattern on DWI and dynamic phases, and size discrepancy between sequences by consensus of two observers. Multivariate analysis revealed that the following significant parameters favour microabscess: a history of bile duct cancer, perilesional hyperaemia, persistent arterial rim enhancement through the transitional phase (TP), and size discrepancy between T1WI and T2WI and between T1WI and hepatobiliary phase image (HBPI). The diagnostic accuracy for microabscess was highest (90.9%) when showing a size discrepancy ≥30% between T1WI and HBPI or persistent arterial rim enhancement through the TP. When the lesion was positive for both these variables, specificity reached 100%. The combination of a size discrepancy between T1WI and HBPI and persistent arterial rim enhancement through the TP represents a reliable MRI feature for distinguishing between hepatic microabscess and metastasis in patients with periampullary cancer. (orig.)

  17. Hepatic farnesoid X-receptor isoforms α2 and α4 differentially modulate bile salt and lipoprotein metabolism in mice.

    Directory of Open Access Journals (Sweden)

    Marije Boesjes

    Full Text Available The nuclear receptor FXR acts as an intracellular bile salt sensor that regulates synthesis and transport of bile salts within their enterohepatic circulation. In addition, FXR is involved in control of a variety of crucial metabolic pathways. Four FXR splice variants are known, i.e. FXRα1-4. Although these isoforms show differences in spatial and temporal expression patterns as well as in transcriptional activity, the physiological relevance hereof has remained elusive. We have evaluated specific roles of hepatic FXRα2 and FXRα4 by stably expressing these isoforms using liver-specific self-complementary adeno-associated viral vectors in total body FXR knock-out mice. The hepatic gene expression profile of the FXR knock-out mice was largely normalized by both isoforms. Yet, differential effects were also apparent; FXRα2 was more effective in reducing elevated HDL levels and transrepressed hepatic expression of Cyp8b1, the regulator of cholate synthesis. The latter coincided with a switch in hydrophobicity of the bile salt pool. Furthermore, FXRα2-transduction caused an increased neutral sterol excretion compared to FXRα4 without affecting intestinal cholesterol absorption. Our data show, for the first time, that hepatic FXRα2 and FXRα4 differentially modulate bile salt and lipoprotein metabolism in mice.

  18. Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents

    DEFF Research Database (Denmark)

    Xiao, Fei; Fofana, Isabel; Heydmann, Laura

    2014-01-01

    Hepatitis C virus (HCV) is transmitted between hepatocytes via classical cell entry but also uses direct cell-cell transfer to infect neighboring hepatocytes. Viral cell-cell transmission has been shown to play an important role in viral persistence allowing evasion from neutralizing antibodies....... In contrast, the role of HCV cell-cell transmission for antiviral resistance is unknown. Aiming to address this question we investigated the phenotype of HCV strains exhibiting resistance to direct-acting antivirals (DAAs) in state-of-the-art model systems for cell-cell transmission and spread. Using HCV...... genotype 2 as a model virus, we show that cell-cell transmission is the main route of viral spread of DAA-resistant HCV. Cell-cell transmission of DAA-resistant viruses results in viral persistence and thus hampers viral eradication. We also show that blocking cell-cell transmission using host...

  19. Fatty liver in hepatitis C patients post-sustained virological response with direct-acting antivirals

    Science.gov (United States)

    Noureddin, Mazen; Wong, Micaela M; Todo, Tsuyoshi; Lu, Shelly C; Sanyal, Arun J; Mena, Edward A

    2018-01-01

    AIM To determine steatosis and fibrosis prevalence in hepatitis C patients after a sustained virological response achieved with direct-acting antivirals. METHODS Transient elastography with controlled attenuation parameter (CAP) was used to assess hepatic steatosis post-sustained virological response (SVR); the CAP technology was not available in the United States at study initiation. Liver stiffness/fibrosis was measured before and 47 wk after treatment completion. Patients with genotype 3 and patients with cirrhosis were excluded. RESULTS One hundred and one patients were included in the study. Post-SVR there were decreases from baseline in alanine aminotransferase (ALT) (63.1 to 17.8 U/L), aspartate aminotransferase (51.8 to 21.5 U/L) and fibrosis score (7.4 to 6.1 kPa) (P steatosis on CAP; of these, 6.25% had advanced fibrosis. Patients with steatosis had higher body mass index (29.0 vs 26.1 kg/m2), glucose (107.8 vs 96.6 mg/dL), ALT (20.4 vs 15.3 mg/dL), CAP score (296.3 vs 212.4 dB/m) and fibrosis score (7.0 vs 5.3 kPa); P steatosis had change in fibrosis score post-SVR (7.7 kPa vs 7.0 kPa and 7.0 kPa vs 5.3 kPa); alternatively, (P steatosis continued to have clinically significant stiffness (≥ 7 kPa). CONCLUSION Fatty liver is very common in hepatitis C virus (HCV) patients post-SVR. These patients continue to have elevated mean fibrosis score (≥ 7 kPa) compared to those without fatty liver; some have advanced fibrosis. Long term follow up is needed to assess steatosis and fibrosis in HCV patients post-SVR. PMID:29568207

  20. Differential hepatic avoidance radiation therapy: Proof of concept in hepatocellular carcinoma patients

    International Nuclear Information System (INIS)

    Bowen, Stephen R.; Saini, Jatinder; Chapman, Tobias R.; Miyaoka, Robert S.; Kinahan, Paul E.; Sandison, George A.; Wong, Tony; Vesselle, Hubert J.; Nyflot, Matthew J.; Apisarnthanarax, Smith

    2015-01-01

    Purpose: To evaluate the feasibility of a novel planning concept that differentially redistributes RT dose away from functional liver regions as defined by 99m Tc-sulphur colloid (SC) uptake on patient SPECT/CT images. Materials and methods: Ten HCC patients with different Child–Turcotte–Pugh scores (A5-B9) underwent SC SPECT/CT scans in treatment position prior to RT that were registered to planning CT scans. Proton pencil beam scanning (PBS) therapy plans were optimized to deliver 37.5–60.0 Gy (RBE) over 5–15 fractions using single field uniform dose technique robust to range and setup uncertainty. Photon volumetrically modulated arc therapy (VMAT) plans were optimized to the same prescribed dose and minimum target coverage. For both treatment modalities, differential hepatic avoidance RT (DHART) plans were generated to decrease dose to functional liver volumes (FLV) defined by a range of thresholds relative to maximum SC uptake (43–90%) in the tumor-subtracted liver. Radiation dose was redistributed away from regions of increased SC uptake in each FLV by linearly scaling mean dose objectives during PBS or VMAT optimization. DHART planning feasibility was assessed by a significantly negative Spearman’s rank correlation (R S ) between dose difference and SC uptake. Patient, tumor, and treatment planning characteristics were tested for association to DHART planning feasibility using non-parametric Kruskal–Wallis ANOVA. Results: Compared to conventional plans, DHART plans achieved a 3% FLV dose reduction for every 10% SC uptake increase. DHART planning was feasible in the majority of patients with 60% of patients having R S < −0.5 (p < 0.01, range −1.0 to 0.2) and was particularly effective in 30% of patients (R S < −0.9). Mean dose to FLV was reduced by up to 20% in these patients. Only fractionation regimen was associated with DHART planning feasibility: 15 fraction courses were more feasible than 5–6 fraction courses (R S < −0.93 vs. R S

  1. Hepatitis C virus resistance to the new direct-acting antivirals.

    Science.gov (United States)

    Esposito, Isabella; Trinks, Julieta; Soriano, Vicente

    2016-10-01

    The treatment of hepatitis C virus (HCV) infection has dramatically improved in recent years with the widespread use of interferon-free combination regimens. Despite the high sustained virological response (SVR) rates (over 90%) obtained with direct-acting antivirals (DAAs), drug resistance has emerged as a potential challenge. The high replication rate of HCV and the low fidelity of its RNA polymerase result in a high degree of genetic variability in the HCV population, which ultimately explains the rapid selection of drug resistance associated variants (RAVs). Results from clinical trials and real-world experience have both provided important information on the rate and clinical significance of RAVs. They can be present in treatment-naive patients as natural polymorphisms although more frequently they are selected upon treatment failure. In patients engaged in high-risk behaviors, RAVs can be transmitted. Although DAA failures generally occur in less than 10% of treated chronic hepatitis C patients, selection of drug resistance is the rule in most cases. HCV re-treatment options are available, but first-line therapeutic strategies should be optimized to efficiently prevent DAA failure due to baseline HCV resistance. Considerable progress is being made and next-generation DAAs are coming with pangenotypic activity and higher resistance barrier.

  2. Treatment of chronic hepatitis C with direct-acting antivirals: The role of resistance.

    Science.gov (United States)

    Jiménez-Pérez, Miguel; González-Grande, Rocío; España Contreras, Pilar; Pinazo Martínez, Isabel; de la Cruz Lombardo, Jesús; Olmedo Martín, Raúl

    2016-08-07

    The use of direct-acting antivirals (DAAs) to treat chronic hepatitis C has resulted in a significant increase in rates of sustained viral response (around 90%-95%) as compared with the standard treatment of peginterferon/ribavirin. Despite this, however, the rates of therapeutic failure in daily clinical practice range from 10%-15%. Most of these cases are due to the presence of resistant viral variants, resulting from mutations produced by substitutions of amino acids in the viral target protein that reduce viral sensitivity to DAAs, thus limiting the efficacy of these drugs. The high genetic diversity of hepatitis C virus has resulted in the existence of resistance-associated variants (RAVs), sometimes even before starting treatment with DAAs, though generally at low levels. These pre-existing RAVs do not appear to impact on the sustained viral response, whereas those that appear after DAA therapy could well be determinant in virological failure with future treatments. As well as the presence of RAVs, virological failure to treatment with DAAs is generally associated with other factors related with a poor response, such as the degree of fibrosis, the response to previous therapy, the viral load or the viral genotype. Nonetheless, viral breakthrough and relapse can still occur in the absence of detectable RAVs and after the use of highly effective DAAs, so that the true clinical impact of the presence of RAVs in therapeutic failure remains to be determined.

  3. Evaluation and Management of Hepatic Encephalopathy: Current Status and Future Directions

    OpenAIRE

    Suraweera, Duminda; Sundaram, Vinay; Saab, Sammy

    2016-01-01

    Hepatic encephalopathy is a spectrum of neurocognitive manifestations often seen in patients with liver injury or rarely in patients with portosystemic shunting without liver injury. It can be divided into minimal (covert) hepatic encephalopathy and overt hepatic encephalopathy, depending on the severity. Patients with hepatic encephalopathy have compromised clinical outcomes, decreased quality of life, and increased healthcare utilization, often resulting in a heavy financial and personal bu...

  4. [A new challenge in clinical practice: resistance to directly acting antivirals in hepatitis C treatment].

    Science.gov (United States)

    Chen, Z W; Hu, P; Ren, H

    2016-03-20

    Directly acting antivirals (DAAs) is a major treatment of hepatitis C virus (HCV) overseas. But DAAs resistance is getting more and more clinicians' attention. DAAs have not been approved in China to date, even though some of them are in clinical trials. However, a good knowledge of DAAs resistance is important on optimizing HCV treatment regimens, increasing sustained virological response (SVR) and decreasing treatment failure in clinical. In this review, DAAs resistance mechanism and virologic barrier to resistance, the prevalence of pre-existing DAAs resistance-associated variants (RAVs), the impact of RAVs on treatment outcome, the options of treatment regimens after resistance and drug resistance testing are discussed, hoping to provide some help for DAAs' standardized treatment in China in the future.

  5. Evaluation and Management of Hepatic Encephalopathy: Current Status and Future Directions

    Science.gov (United States)

    Suraweera, Duminda; Sundaram, Vinay; Saab, Sammy

    2016-01-01

    Hepatic encephalopathy is a spectrum of neurocognitive manifestations often seen in patients with liver injury or rarely in patients with portosystemic shunting without liver injury. It can be divided into minimal (covert) hepatic encephalopathy and overt hepatic encephalopathy, depending on the severity. Patients with hepatic encephalopathy have compromised clinical outcomes, decreased quality of life, and increased healthcare utilization, often resulting in a heavy financial and personal burden on caregivers. The diagnosis remains largely clinical, with the exclusion of possible other causes for the altered mental status. Current treatment strategies include nonabsorbable disaccharides and antibiotics. This review will focus on the diagnosis, management and clinical impact of hepatic encephalopathy. PMID:27377741

  6. Directional differentiation of chicken embryonic stem cells into ...

    African Journals Online (AJOL)

    Chicken embryonic stem (ES) cells are useful for producing transgenic chickens and preserving genetic material in avian species. In this study, the differentiation potential of chicken ES cells was investigated in vitro. Chicken ES cells were differentiated into osteoblasts cultured for 15 to 21 days in the induction media ...

  7. Effect of Chromatin-Remodeling Agents in Hepatic Differentiation of Rat Bone Marrow-Derived Mesenchymal Stem Cells In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Danna Ye

    2016-01-01

    Full Text Available Epigenetic events, including covalent histone modifications and DNA methylation, play fundamental roles in the determination of lineage-specific gene expression and cell fates. The aim of this study was to determine whether the DNA methyltransferase inhibitor (DNMTi 5-aza-2′-deoxycytidine (5-aza-dC and the histone deacetylase inhibitor (HDACi trichostatin A (TSA promote the hepatic differentiation of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs and their therapeutic effect on liver damage. 1 μM TSA and 20 μM 5-aza-dC were added to standard hepatogenic medium especially at differentiation and maturation steps and their potential function on hepatic differentiation in vitro and in vivo was determined. Exposure of rBM-MSCs to 1 μM TSA at both the differentiation and maturation steps considerably improved hepatic differentiation. TSA enhanced the development of the hepatocyte shape, promoted the chronological expression of hepatocyte-specific markers, and improved hepatic functions. In contrast, treatment of rBM-MSCs with 20 μM 5-aza-dC alone or in combination with TSA was ineffective in improving hepatic differentiation in vitro. TSA and/or 5-aza-dC derived hepatocytes-like cells failed to improve the therapeutic potential in liver damage. We conclude that HDACis enhance hepatic differentiation in a time-dependent manner, while DNMTis do not induce the hepatic differentiation of rBM-MSCs in vitro. Their in vivo function needs further investigation.

  8. Hepatocyte nuclear factor 4A improves hepatic differentiation of immortalized adult human hepatocytes and improves liver function and survival.

    Science.gov (United States)

    Hang, Hua-Lian; Liu, Xin-Yu; Wang, Hai-Tian; Xu, Ning; Bian, Jian-Min; Zhang, Jian-Jun; Xia, Lei; Xia, Qiang

    2017-11-15

    Immortalized human hepatocytes (IHH) could provide an unlimited supply of hepatocytes, but insufficient differentiation and phenotypic instability restrict their clinical application. This study aimed to determine the role of hepatocyte nuclear factor 4A (HNF4A) in hepatic differentiation of IHH, and whether encapsulation of IHH overexpressing HNF4A could improve liver function and survival in rats with acute liver failure (ALF). Primary human hepatocytes were transduced with lentivirus-mediated catalytic subunit of human telomerase reverse transcriptase (hTERT) to establish IHH. Cells were analyzed for telomerase activity, proliferative capacity, hepatocyte markers, and tumorigenicity (c-myc) expression. Hepatocyte markers, hepatocellular functions, and morphology were studied in the HNF4A-overexpressing IHH. Hepatocyte markers and karyotype analysis were completed in the primary hepatocytes using shRNA knockdown of HNF4A. Nuclear translocation of β-catenin was assessed. Rat models of ALF were treated with encapsulated IHH or HNF4A-overexpressing IHH. A HNF4A-positive IHH line was established, which was non-tumorigenic and conserved properties of primary hepatocytes. HNF4A overexpression significantly enhanced mRNA levels of genes related to hepatic differentiation in IHH. Urea levels were increased by the overexpression of HNF4A, as measured 24h after ammonium chloride addition, similar to that of primary hepatocytes. Chromosomal abnormalities were observed in primary hepatocytes transfected with HNF4A shRNA. HNF4α overexpression could significantly promote β-catenin activation. Transplantation of HNF4A overexpressing IHH resulted in better liver function and survival of rats with ALF compared with IHH. HNF4A improved hepatic differentiation of IHH. Transplantation of HNF4A-overexpressing IHH could improve the liver function and survival in a rat model of ALF. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Delay differential equations recent advances and new directions

    CERN Document Server

    Balachandran, Balakumar; Gilsinn, David E

    2009-01-01

    This is a cohesive set of contributions from leading experts on the theory and applications of functional and delay differential equations. The book focuses on theory, symbolic, and numerical methods, which show the practical applications of the concepts.

  10. Fatty liver in hepatitis C patients post-sustained virological response with direct-acting antivirals.

    Science.gov (United States)

    Noureddin, Mazen; Wong, Micaela M; Todo, Tsuyoshi; Lu, Shelly C; Sanyal, Arun J; Mena, Edward A

    2018-03-21

    To determine steatosis and fibrosis prevalence in hepatitis C patients after a sustained virological response achieved with direct-acting antivirals. Transient elastography with controlled attenuation parameter (CAP) was used to assess hepatic steatosis post-sustained virological response (SVR); the CAP technology was not available in the United States at study initiation. Liver stiffness/fibrosis was measured before and 47 wk after treatment completion. Patients with genotype 3 and patients with cirrhosis were excluded. One hundred and one patients were included in the study. Post-SVR there were decreases from baseline in alanine aminotransferase (ALT) (63.1 to 17.8 U/L), aspartate aminotransferase (51.8 to 21.5 U/L) and fibrosis score (7.4 to 6.1 kPa) ( P < 0.05). Post-SVR, 48 patients (47.5%) had steatosis on CAP; of these, 6.25% had advanced fibrosis. Patients with steatosis had higher body mass index (29.0 vs 26.1 kg/m 2 ), glucose (107.8 vs 96.6 mg/dL), ALT (20.4 vs 15.3 mg/dL), CAP score (296.3 vs 212.4 dB/m) and fibrosis score (7.0 vs 5.3 kPa); P < 0.05. Interestingly, compared to baseline, both patients with and without steatosis had change in fibrosis score post-SVR (7.7 kPa vs 7.0 kPa and 7.0 kPa vs 5.3 kPa); alternatively, ( P < 0.05) and therefore patients with steatosis continued to have clinically significant stiffness (≥ 7 kPa). Fatty liver is very common in hepatitis C virus (HCV) patients post-SVR. These patients continue to have elevated mean fibrosis score (≥ 7 kPa) compared to those without fatty liver; some have advanced fibrosis. Long term follow up is needed to assess steatosis and fibrosis in HCV patients post-SVR.

  11. DIFFERENTIAL HEPATIC PROCESSING AND BILIARY-SECRETION OF HEADGROUP AND ACYL CHAINS OF LIPOSOMAL PHOSPHATIDYLCHOLINES

    NARCIS (Netherlands)

    VERKADE, HJ; DERKSEN, JTP; GERDING, A; SCHERPHOF, GL; VONK, RJ; KUIPERS, F

    1991-01-01

    To investigate the contribution of plasma-derived phosphatidylcholine (PC) to bile PC, the hepatic processing and biliary secretion of liposome-associated PC was studied in rats. For this purpose, small unilamellar vesicles (SUV), containing trace amounts of

  12. Application of dual phase imaging of 11C-acetate positron emission tomography on differential diagnosis of small hepatic lesions.

    Directory of Open Access Journals (Sweden)

    Li Huo

    Full Text Available OBJECTIVE: Previously we observed that dual phase 11C-acetate positron emission tomography (AC-PET could be employed for differential diagnosis of liver malignancies. In this study, we prospectively evaluated the effect of dual phase AC-PET on differential diagnosis of primary hepatic lesions of 1-3 cm in size. METHODS: 33 patients having primary hepatic lesions with size of 1-3 cm in diameter undertook dual phase AC-PET scans. Procedure included an early upper-abdomen scan immediately after tracer injection and a conventional scan in 11-18 min. The standardized uptake value (SUV was calculated for tumor (SUVT and normal tissue (SUVB, from which 11C-acetate uptake ratio (as lesion against normal liver tissue, SUVT/SUVB in early imaging (R1, conventional imaging (R2, and variance between R2 and R1 (ΔR were derived. Diagnoses based on AC-PET data and histology were compared. Statistical analysis was performed with SPSS 19.0. RESULTS: 20 patients were found to have HCC and 13 patients had benign tumors. Using ΔR>0 as criterion for malignancy, the accuracy and specificity were significantly increased comparing with conventional method. The area under ROC curve (AUC for R1, R2, and ΔR were 0.417, 0.683 and 0.831 respectively. Differential diagnosis between well-differentiated HCCs and benign lesions of FNHs and hemangiomas achieved 100% correct. Strong positive correlation was also found between R1 and R2 in HCC (r2 = 0.55, P<0.001. CONCLUSIONS: Dual phase AC-PET scan is a useful procedure for differential diagnosis of well-differentiated hepatocellular carcinoma and benign lesions. The dynamic changes of 11C-acetate uptake in dual phase imaging provided key information for final diagnosis.

  13. Directed Differentiation of Zebrafish Pluripotent Embryonic Cells to Functional Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Yao Xiao

    2016-09-01

    Full Text Available A cardiomyocyte differentiation in vitro system from zebrafish embryos remains to be established. Here, we have determined pluripotency window of zebrafish embryos by analyzing their gene-expression patterns of pluripotency factors together with markers of three germ layers, and have found that zebrafish undergoes a very narrow period of pluripotency maintenance from zygotic genome activation to a brief moment after oblong stage. Based on the pluripotency and a combination of appropriate conditions, we established a rapid and efficient method for cardiomyocyte generation in vitro from primary embryonic cells. The induced cardiomyocytes differentiated into functional and specific cardiomyocyte subtypes. Notably, these in vitro generated cardiomyocytes exhibited typical contractile kinetics and electrophysiological features. The system provides a new paradigm of cardiomyocyte differentiation from primary embryonic cells in zebrafish. The technology provides a new platform for the study of heart development and regeneration, in addition to drug discovery, disease modeling, and assessment of cardiotoxic agents.

  14. Directed Differentiation of Human Pluripotent Stem Cells to Microglia

    Directory of Open Access Journals (Sweden)

    Panagiotis Douvaras

    2017-06-01

    Full Text Available Microglia, the immune cells of the brain, are crucial to proper development and maintenance of the CNS, and their involvement in numerous neurological disorders is increasingly being recognized. To improve our understanding of human microglial biology, we devised a chemically defined protocol to generate human microglia from pluripotent stem cells. Myeloid progenitors expressing CD14/CX3CR1 were generated within 30 days of differentiation from both embryonic and induced pluripotent stem cells (iPSCs. Further differentiation of the progenitors resulted in ramified microglia with highly motile processes, expressing typical microglial markers. Analyses of gene expression and cytokine release showed close similarities between iPSC-derived (iPSC-MG and human primary microglia as well as clear distinctions from macrophages. iPSC-MG were able to phagocytose and responded to ADP by producing intracellular Ca2+ transients, whereas macrophages lacked such response. The differentiation protocol was highly reproducible across several pluripotent stem cell lines.

  15. Direct-Acting Antivirals for the Treatment of Chronic Hepatitis C: Open Issues and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Hee Bok Chae

    2013-01-01

    Full Text Available Currently, two direct-acting antivirals (DAAs show well-established efficacy against hepatitis C virus (HCV, namely, first-wave protease inhibitors telaprevir and boceprevir. Most clinical trials have examined DAAs in combination with standard of care (SOC regimens. Future therapeutic drugs were divided into three categories. They are second-wave protease inhibitors, second-generation protease inhibitors, and polymerase inhibitors. Second-wave protease inhibitors are more improved form and can be administered once a day. Oral drug combinations can be favored because interferon (IFN not only has to be given as intradermal injection, but also can cause several serious side effects. Combination of drugs with different mechanisms shows a good sustained virological response (SVR. But several mutations are associated with viral resistance to DAAs. Therefore, genotypic resistance data may provide insights into strategies aimed at maximizing SVR rates and minimizing resistance. Combined drug regimens are necessary to prevent the emergence of drug-resistant HCV. Many promising DAA candidates have been identified. Of these, a triple regimen containing sofosbuvir shows promise, and treatment with daclatasvir plus asunaprevir yields a high SVR rate (95%. Oral drug combinations will be standard of care in the near future.

  16. Resistance Mechanisms in Hepatitis C Virus: implications for Direct-Acting Antiviral Use.

    Science.gov (United States)

    Bagaglio, Sabrina; Uberti-Foppa, Caterina; Morsica, Giulia

    2017-07-01

    Multiple direct-acting antiviral (DAA)-based regimens are currently approved that provide one or more interferon-free treatment options for hepatitis C virus (HCV) genotypes (G) 1-6. The choice of a DAA regimen, duration of therapy, and use of ribavirin depends on multiple viral and host factors, including HCV genotype, the detection of resistance-associated amino acid (aa) substitutions (RASs), prior treatment experience, and presence of cirrhosis. In regard to viral factors that may guide the treatment choice, the most important is the infecting genotype because a number of DAAs are genotype-designed. The potency and the genetic barrier may also impact the choice of treatment. One important and debated possible virologic factor that may negatively influence the response to DAAs is the presence of baseline RASs. Baseline resistance testing is currently not routinely considered or recommended for initiating HCV treatment, due to the overall high response rates (sustained virological response >90%) obtained. Exceptions are patients infected by HCV G1a when initiating treatment with simeprevir and elbasvir/grazoprevir or in those with cirrhosis prior to daclatasvir/sofosbuvir treatment because of natural polymorphisms demonstrated in sites of resistance. On the basis of these observations, first-line strategies should be optimized to overcome treatment failure due to HCV resistance.

  17. Hepatitis C Virus Resistance to Direct-Acting Antiviral Drugs in Interferon-Free Regimens.

    Science.gov (United States)

    Pawlotsky, Jean-Michel

    2016-07-01

    Treatment of hepatitis C virus (HCV) infection has progressed considerably with the approval of interferon-free, direct-acting antiviral (DAA)-based combination therapies. Although most treated patients achieve virological cure, HCV resistance to DAAs has an important role in the failure of interferon-free treatment regimens. The presence of viral variants resistant to NS5A inhibitors at baseline is associated with lower rates of virological cure in certain groups of patients, such as those with genotype 1a or 3 HCV, those with cirrhosis, and/or prior nonresponders to pegylated interferon-based regimens. DAA-resistant HCV is generally dominant at virological failure (most often relapse). Viruses resistant to NS3-4A protease inhibitors disappear from peripheral blood in a few weeks to months, whereas NS5A inhibitor-resistant viruses persist for years. Re-treatment options are available, but first-line treatment strategies should be optimized to efficiently prevent treatment failure due to HCV resistance. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  18. Reactivation of Herpesvirus in Patients With Hepatitis C Treated With Direct-Acting Antiviral Agents.

    Science.gov (United States)

    Perelló M, Christie; Fernández-Carrillo, Carlos; Londoño, María-Carlota; Arias-Loste, Teresa; Hernández-Conde, Marta; Llerena, Susana; Crespo, Javier; Forns, Xavier; Calleja, José Luis

    2016-11-01

    We performed a case-series analysis of reactivation of herpesvirus in patients with hepatitis C virus (HCV) infection treated with direct-acting antiviral (DAA) agents. We collected data from 576 patients with HCV infection treated with DAA combinations at 3 hospitals in Spain, from November 2014 through November 2015. We also collected data from a control population (230 HCV-infected patients, matched for sex and age; 23 untreated and 213 treated with interferon-based regimens). Herpesvirus was reactivated in 10 patients who received DAA therapy (7 patients had cirrhosis and 3 patients had received liver transplants), a median of 8 weeks after the therapy was initiated. None of the controls had herpesvirus reactivation. Patients with herpesvirus reactivation were receiving the DAA agents sofosbuvir with ledipasvir (with or without ribavirin, 7/10), ombitasvir with paritaprevir and ritonavir plus dasabuvir (with or without ribavirin, 2/10), or sofosbuvir with simeprevir plus ribavirin (1/10). Two of the 10 patients developed postherpetic neuralgia and 1 patient developed kerato-uveitis. All 10 patients with herpesvirus reactivation achieved a sustained virologic response. Immune changes that follow clearance of HCV might lead to reactivation of other viruses, such as herpesvirus. Patients with HCV infection suspected of having herpesvirus infection should be treated immediately. Some groups also might be screened for herpesvirus infection. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  19. Effect of contrast-enhanced ultrasound on differential diagnosis of intrahepatic cholangiocarcinoma and arterial phase enhanced hepatic inflammatory lesions

    Institute of Scientific and Technical Information of China (English)

    Shanshan Yin; Qiuli Cui; Kun Yan; Wei Yang; Wei Wu; Liping Bao; Minhua Chen

    2017-01-01

    Objective:To investigate differential diagnosis between intrahepatic cholangiocarcinoma (ICC) and arterial phase enhanced hepatic inflammatory lesions in patients without liver cirrhosis using contrast-enhanced ultrasound (CEUS).Methods:ICC and hepatic inflammatory lesions cases with CEUS and pathological diagnosis between Sep 2013 and Oct 2016 were investigated retrospectively.Imaging features of conventional ultrasound and CEUS were analyzed.The parameters of time intensity curve (TIC),including the arrival time,peak intensity (PI) in the lesions,the starting time for washout,and the intensity difference at 3 min (△I3) after contrast agent infection between the lesion and the liver parenchyma,were compared between ICC and hepatic inflammatory lesions.Results:Twenty-five ICC and fifteen inflammatory patients were included in this study.Seventeen ICC (68.0%) and two inflammatory cases (13.3%) showed bile duct dilatation on conventional ultrasound.Using CEUS,three ICC cases (12.0%) were misdiagnosed as inflammatory lesions and three inflammatory lesions (20.0%) as ICC;two ICC (8.0%) and one inflammatory case (6.7%) could not be made definite diagnosis.Washout started at 34.5±3.5 s and 61.5± 12.9 s for ICC and inflammatory lesions respectively (P<0.001).The intensity difference between lesion and liver parenchyma at 3 min after contrast agent injection was 10.8±3.1 dB in ICC and 4.2±2.3 dB in inflammatory group (P<0.00 1).The sensitivity and specificity differentiating ICC and inflammatory lesions were 76% and 87% if the cut-offvalue of the intensity difference was 7.7 dB.Conclusions:Combined with TIC analysis,and particularly with the characteristic of the early-starting and obvious washout in ICC,CEUS can be useful in differential diagnosis between hepatic inflammatory lesions and ICC.

  20. Role of diffusion-weighted MRI in differentiation of hepatic abscesses from non-infected fluid collections.

    Science.gov (United States)

    Schmid-Tannwald, C; Schmid-Tannwald, C M; Morelli, J N; Neumann, R; Reiser, M F; Nikolaou, K; Rist, C

    2014-07-01

    To evaluate the role of diffusion-weighted magnetic resonance imaging (DW-MRI) in the differentiation of hepatic abscesses from non-infected fluid collections. In this retrospective study, 22 hepatic abscesses and 27 non-infected hepatic fluid collections were examined in 27 patients who underwent abdominal MRI including DW-MRI. Two independent observers reviewed T2-weighted + DW-MRI and T2-weighted + contrast-enhanced T1-weighted (CET1W) images in two sessions. Detection rates and confidence levels were calculated and compared using McNemar's and Wilcoxon's signed rank tests, respectively. Apparent diffusion coefficient (ADC) values of abscesses and non-infected fluid collections were compared using the t-test. Receiver operating characteristic (ROC) curves were constructed. There was no statistically significant difference in the accuracy of detecting abscesses using T2-weighted + DW-MRI (both observers: 21/22, 95.5%) versus T2-weighted + CET1W images (observer 1: 21/22, 95.5%; observer 2: 22/22, 100%; p collections (0.83 ± 0.24 versus 2.25 ± 0.61 × 10(-3) mm(2)/s; p collections at a threshold ADC value of 1.36 × 10(-3) mm(2)/s. DW-MRI allows qualitative and quantitative differentiation of abscesses from non-infected fluid collections in the liver. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  1. Differential effects of high-carbohydrate and high-fat diets on hepatic lipogenesis in rats.

    Science.gov (United States)

    Ferramosca, Alessandra; Conte, Annalea; Damiano, Fabrizio; Siculella, Luisa; Zara, Vincenzo

    2014-06-01

    Hepatic fatty acid synthesis is influenced by several nutritional and hormonal factors. In this study, we have investigated the effects of distinct experimental diets enriched in carbohydrate or in fat on hepatic lipogenesis. Male Wistar rats were divided into four groups and fed distinct experimental diets enriched in carbohydrates (70% w/w) or in fat (20 and 35% w/w). Activity and expression of the mitochondrial citrate carrier and of the cytosolic enzymes acetyl-CoA carboxylase and fatty acid synthetase were analyzed through the study with assessments at 0, 1, 2, 4, and 6 weeks. Liver lipids and plasma levels of lipids, glucose, and insulin were assayed in parallel. Whereas the high-carbohydrate diet moderately stimulated hepatic lipogenesis, a strong inhibition of this anabolic pathway was found in animals fed high-fat diets. This inhibition was time-dependent and concentration-dependent. Moreover, whereas the high-carbohydrate diet induced an increase in plasma triglycerides, the high-fat diets determined an accumulation of triglycerides in liver. An increase in the plasmatic levels of glucose and insulin was observed in all cases. The excess of sucrose in the diet is converted into fat that is distributed by bloodstream in the organism in the form of circulating triglycerides. On the other hand, a high amount of dietary fat caused a strong inhibition of lipogenesis and a concomitant increase in the level of hepatic lipids, thereby highlighting, in these conditions, the role of liver as a reservoir of exogenous fat.

  2. Lipids in hepatic glycogen storage diseases: pathophysiology, monitoring of dietary management and future directions.

    Science.gov (United States)

    Derks, Terry G J; van Rijn, Margreet

    2015-05-01

    Hepatic glycogen storage diseases (GSD) underscore the intimate relationship between carbohydrate and lipid metabolism. The hyperlipidemias in hepatic GSD reflect perturbed intracellular metabolism, providing biomarkers in blood to monitor dietary management. In different types of GSD, hyperlipidemias are of a different origin. Hypertriglyceridemia is most prominent in GSD type Ia and associated with long-term outcome morbidity, like pancreatitis and hepatic adenomas. In the ketotic subtypes of GSD, hypertriglyceridemia reflects the age-dependent fasting intolerance, secondary lipolysis and increased mitochondrial fatty acid oxidation. The role of high protein diets is established for ketotic types of GSD, but non-traditional dietary interventions (like medium-chain triglycerides and the ketogenic diet) in hepatic GSD are still controversial and necessitate further studies. Patients with these rare inherited disorders of carbohydrate metabolism meet several criteria of the metabolic syndrome, therefore close monitoring for cardiovascular diseases in ageing GSD patients may be justified.

  3. Directed technical change and differentiation of climate policy

    NARCIS (Netherlands)

    Otto, V.M.; Löschel, A.; Reilly, J.

    2008-01-01

    This paper studies the cost effectiveness of climate policy if there are technology externalities. For this purpose, we develop a forward looking model that captures empirical links between CO2 emissions associated with energy use, directed technical change and the economy. We find our most cost

  4. Direct-acting antiviral therapy decreases hepatocellular carcinoma recurrence rate in cirrhotic patients with chronic hepatitis C.

    Science.gov (United States)

    Virlogeux, Victor; Pradat, Pierre; Hartig-Lavie, Kerstin; Bailly, François; Maynard, Marianne; Ouziel, Guillaume; Poinsot, Domitille; Lebossé, Fanny; Ecochard, Marie; Radenne, Sylvie; Benmakhlouf, Samir; Koffi, Joseph; Lack, Philippe; Scholtes, Caroline; Uhres, Anne-Claire; Ducerf, Christian; Mabrut, Jean-Yves; Rode, Agnès; Levrero, Massimo; Combet, Christophe; Merle, Philippe; Zoulim, Fabien

    2017-08-01

    Arrival of direct-acting antiviral agents against hepatitis C virus with high-sustained virological response rates and very few side effects has drastically changed the management of hepatitis C virus infection. The impact of direct-acting antiviral exposure on hepatocellular carcinoma recurrence after a first remission in patients with advanced fibrosis remains to be clarified. 68 consecutive hepatitis C virus patients with a first hepatocellular carcinoma diagnosis and under remission, subsequently treated or not with a direct-acting antiviral combination, were included. Clinical, biological and virological data were collected at first hepatocellular carcinoma diagnosis, at remission and during the surveillance period. All patients were cirrhotic. Median age was 62 years and 76% of patients were male. Twenty-three patients (34%) were treated with direct-acting antivirals and 96% of them achieved sustained virological response. Median time between hepatocellular carcinoma remission and direct-acting antivirals initiation was 7.2 months (IQR: 3.6-13.5; range: 0.3-71.4) and median time between direct-acting antivirals start and hepatocellular carcinoma recurrence was 13.0 months (IQR: 9.2-19.6; range: 3.0-24.7). Recurrence rate was 1.7/100 person-months among treated patients vs 4.2/100 person-months among untreated patients (P=.008). In multivariate survival analysis, the hazard ratio for hepatocellular carcinoma recurrence after direct-acting antivirals exposure was 0.24 (95% confidence interval: 0.10-0.55; PHepatocellular carcinoma recurrence rate was significantly lower among patients treated with direct-acting antivirals compared with untreated patients. Given the potential impact of our observation, large-scale prospective cohort studies are needed to confirm these results. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Proteins Differentially Expressed in the Pancreas of Hepatic Alcohol Dehydrogenase-Deficient Deer Mice Fed Ethanol For 3 Months.

    Science.gov (United States)

    Bhopale, Kamlesh K; Amer, Samir M; Kaphalia, Lata; Soman, Kizhake V; Wiktorowicz, John E; Shakeel Ansari, Ghulam A; Kaphalia, Bhupendra S

    2017-07-01

    The aim of this study was to identify differentially expressed proteins in the pancreatic tissue of hepatic alcohol dehydrogenase-deficient deer mice fed ethanol to understand metabolic basis and mechanism of alcoholic chronic pancreatitis. Mice were fed liquid diet containing 3.5 g% ethanol daily for 3 months, and differentially expressed pancreatic proteins were identified by protein separation using 2-dimensional gel electrophoresis and identification by mass spectrometry. Nineteen differentially expressed proteins were identified by applying criteria established for protein identification in proteomics. An increased abundance was found for ribosome-binding protein 1, 60S ribosomal protein L31-like isoform 1, histone 4, calcium, and adenosine triphosphate (ATP) binding proteins and the proteins involved in antiapoptotic processes and endoplasmic reticulum function, stress, and/or homeostasis. Low abundance was found for endoA cytokeratin, 40S ribosomal protein SA, amylase 2b isoform precursor, serum albumin, and ATP synthase subunit β and the proteins involved in cell motility, structure, and conformation. Chronic ethanol feeding in alcohol dehydrogenase-deficient deer mice differentially expresses pancreatic functional and structural proteins, which can be used to develop biomarker(s) of alcoholic chronic pancreatitis, particularly amylase 2b precursor, and 60 kDa heat shock protein and those involved in ATP synthesis and blood osmotic pressure.

  6. Efficacy and Safety of Direct Acting Antivirals in Kidney Transplant Recipients with Chronic Hepatitis C Virus Infection

    OpenAIRE

    Lin, Ming V.; Sise, Meghan E.; Pavlakis, Martha; Amundsen, Beth M.; Chute, Donald; Rutherford, Anna E.; Chung, Raymond T.; Curry, Michael P.; Hanifi, Jasmine M.; Gabardi, Steve; Chandraker, Anil; Heher, Eliot C.; Elias, Nahel; Riella, Leonardo V.

    2016-01-01

    The prevalence of Hepatitis C Virus (HCV) infection is significantly higher in patients with end-stage renal disease compared to the general population and poses important clinical challenges in patients who undergo kidney transplantation. Historically, interferon-based treatment options have been limited by low rates of efficacy and significant side effects, including risk of precipitating rejection. Limited data exist on the use of all-oral, interferon-free direct-acting antiviral (DAA) the...

  7. Direct-acting antiviral agent efficacy and safety in renal transplant recipients with chronic hepatitis C virus infection

    OpenAIRE

    Chen, Keliang; Lu, Pei; Song, Rijin; Zhang, Jiexiu; Tao, Rongzhen; Wang, Zijie; Zhang, Wei; Gu, Min

    2017-01-01

    Abstract Background: The efficacy and safety of direct-acting antivirals (DAAs) for treating hepatitis C virus (HCV)-infected renal transplant recipients (RTRs) has not been determined. Methods: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials and assessed the quality of eligible studies using the Joanna Briggs Institute scale. DAA efficacy and safety were assessed using standard mean difference (SMD) with 95% confidence intervals (95%CIs). Results: Six studi...

  8. Impact of hepatitis C virus genotype-4 eradication following direct acting antivirals on liver stiffness measurement

    Directory of Open Access Journals (Sweden)

    Tag-Adeen M

    2017-10-01

    Full Text Available Mohammed Tag-Adeen,1,2 Ahlam Mohamed Sabra,1 Yuko Akazawa,2 Ken Ohnita,2 Kazuhiko Nakao2 1Department of Internal Medicine, Qena School of Medicine, South Valley University, Qena, Egypt; 2Department of Gastroenterology and Hepatology, Nagasaki School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan Background: Liver fibrosis is the most important prognostic factor in chronic hepatitis C virus (HCV patients, and Egypt shows the highest worldwide HCV prevalence with genotype-4 predominance. The aim of this study was to investigate the degree of liver stiffness measurement (LSM improvement after successful HCV eradication.Patients and methods: The study included 84 chronic HCV Egyptian patients, and was conducted at Qena University Hospital from November 1, 2015 till October 31, 2016. LSM was obtained by FibroScan® before starting direct acting antiviral (DAA treatment and after achieving sustained virologic response-24 (SVR-24. Based on baseline LSM, patients were stratified into F0–F1, F2, F3 and F4 groups (METAVIR. LSM and laboratory data after achieving SVR-24 was compared with that before starting therapy in each fibrosis group (F0-F4, p-value <0.05 was statistically significant.Results: Following DAA treatment, 80 patients achieved SVR-24; of these, 50 were males (62.5%, mean age: 54.2±7.6 years, and mean body mass index: 28.6±2.2 kg/m2. Mean baseline LSM dropped from 15.6±10.8 to 12.1±8.7 kPa post-SVR; the maximum change of −5.8 occurred in F4 versus −2.79, −1.28 and +0.08 in F3, F2 and F0–F1 respectively (p<0.0001. At baseline, 41 patients were in the F4 group; only 16 (39% regressed to non-cirrhotic range (<12.5 kPa, while 25 (61% were still cirrhotic despite achieving SVR-24 (p<0.0001. Patients who achieved LSM improvement (n=64 have had significantly higher baseline aspartate transferase (AST and alanine transaminase (ALT. Also, those patients showed significant improvement in AST, AST/platelets ratio index

  9. Lycopene attenuated hepatic tumorigenesis via differential mechanisms depending on carotenoid cleavage enzyme in mice

    Science.gov (United States)

    Ip, Blanche C.; Liu, Chun; Ausman, Lynne M.; von Lintig, Johannes; Wang, Xiang-Dong

    2014-01-01

    Obesity is associated with increased liver cancer risks and mortality. We recently showed that apo-10’-lycopenoic acid, a lycopene metabolite generated by beta-carotene-9’,10’-oxygenase (BCO2), inhibited carcinogen-initiated, high-fat diet (HFD)-promoted liver inflammation and hepatic tumorigenesis development. The present investigation examined the outstanding question of whether the lycopene could suppress HFD-promoted hepatocellular carcinoma (HCC) progression, and if BCO2 is important in BCO2-knockout (BCO2-KO) and wild-type male mice. Results showed that lycopene supplementation (100 mg/kg diet) for 24 weeks resulted in comparable accumulation of hepatic lycopene (19.4 vs 18.2 nmol/g) and had similar effects on suppressing HFD-promoted HCC incidence (19% vs 20%) and multiplicity (58% vs 62%) in wild-type and BCO2-KO mice, respectively. Intriguingly, lycopene chemopreventive effects in wild-type mice were associated with reduced hepatic pro-inflammatory signaling (phosphorylation of nuclear factor-κB p65 and signal transducer and activator of transcription 3; interleukin-6 protein) and inflammatory foci. In contrast, the protective effects of lycopene in BCO2-KO but not in wild-type mice were associated with reduced hepatic endoplasmic reticulum stress-mediated unfolded protein response (ERUPR), through decreasing ERUPR-mediated protein kinase RNA-activated like kinase– eukaryotic initiation factor 2α activation, and inositol requiring 1α–X-box binding protein 1 signaling. Lycopene supplementation in BCO2-KO mice suppressed oncogenic signals including Met mRNA, β-catenin protein, and mammalian target of rapamycin (mTOR) complex 1 activation, which was associated with increased hepatic microRNA (miR)-199a/b and miR-214 levels. These results provided novel experimental evidence that dietary lycopene can prevent HFD-promoted HCC incidence and multiplicity in mice, and may elicit different mechanisms depending on BCO2 expression. PMID:25293877

  10. A direct algebraic method applied to obtain complex solutions of some nonlinear partial differential equations

    International Nuclear Information System (INIS)

    Zhang Huiqun

    2009-01-01

    By using some exact solutions of an auxiliary ordinary differential equation, a direct algebraic method is described to construct the exact complex solutions for nonlinear partial differential equations. The method is implemented for the NLS equation, a new Hamiltonian amplitude equation, the coupled Schrodinger-KdV equations and the Hirota-Maccari equations. New exact complex solutions are obtained.

  11. Consistency of direct integral estimator for partially observed systems of ordinary differential equations

    NARCIS (Netherlands)

    Vujačić, Ivan; Dattner, Itai

    In this paper we use the sieve framework to prove consistency of the ‘direct integral estimator’ of parameters for partially observed systems of ordinary differential equations, which are commonly used for modeling dynamic processes.

  12. Clarkson-Kruskal Direct Similarity Approach for Differential-Difference Equations

    Institute of Scientific and Technical Information of China (English)

    SHEN Shou-Feng

    2005-01-01

    In this letter, the Clarkson-Kruskal direct method is extended to similarity reduce some differentialdifference equations. As examples, the differential-difference KZ equation and KP equation are considered.

  13. Differential effect of combined lipase deficiency (cld/cld) on human hepatic lipase and lipoprotein lipase secretion.

    Science.gov (United States)

    Boedeker, J C; Doolittle, M H; White, A L

    2001-11-01

    Combined lipase deficiency (cld) is a recessively inherited disorder in mice associated with a deficiency of LPL and hepatic lipase (HL) activity. LPL is synthesized in cld tissues but is retained in the endoplasmic reticulum (ER), whereas mouse HL (mHL) is secreted but inactive. In this study we investigated the effect of cld on the secretion of human HL (hHL) protein mass and activity. Differentiated liver cell lines were derived from cld mice and their normal heterozygous (het) littermates by transformation of hepatocytes with SV40 large T antigen. After transient transfection with lipase expression constructs, secretion of hLPL activity from cld cells was only 12% of that from het cells. In contrast, the rate of secretion of hHL activity and protein mass per unit of expressed hHL mRNA was identical for the two cell lines. An intermediate effect was observed for mHL, with a 46% reduction in secretion of activity from cld cells. The ER glucosidase inhibitor, castanospermine, decreased secretion of both hLPL and hHL from het cells by approximately 70%, but by only approximately 45% from cld cells. This is consistent with data suggesting that cld may result from a reduced concentration of the ER chaperone calnexin. In conclusion, our results demonstrate a differential effect of cld on hLPL, mHL, and hHL secretion, suggesting differential requirements for activation and exit of the enzymes from the ER.

  14. Hepatic Differentiation of Human Induced Pluripotent Stem Cells in a Perfused 3D Porous Polymer Scaffold for Liver Tissue Engineering

    DEFF Research Database (Denmark)

    Hemmingsen, Mette; Muhammad, Haseena Bashir; Mohanty, Soumyaranjan

    A huge shortage of liver organs for transplantation has motivated the research field of tissue engineering to develop bioartificial liver tissue and even a whole liver. The goal of NanoBio4Trans is to create a vascularized bioartificial liver tissue, initially as a liver-support system. Due...... to limitations of primary hepatocytes regarding availability and maintenance of functionality, stem cells and especially human induced pluripotent stem cells (hIPS cells) are an attractive cell source for liver tissue engineering. The aim of this part of NanoBio4Trans is to optimize culture and hepatic...... differentiation of hIPS-derived definitive endoderm (DE) cells in a 3D porous polymer scaffold built-in a perfusable bioreactor. The use of a microfluidic bioreactor array enables the culture of 16 independent tissues in one experimental run and thereby an optimization study to be performed....

  15. Vitamin C and E chronic supplementation differentially affect hepatic insulin signaling in rats.

    Science.gov (United States)

    Ali, Mennatallah A; Eid, Rania M H M; Hanafi, Mervat Y

    2018-02-01

    Vitamin C and vitamin E supplementations and their beneficial effects on type 2 diabetes mellitus (T2DM) have been subjected to countless controversial data. Hence, our aim is to investigate the hepatic molecular mechanisms of any diabetic predisposing risk of the chronic administration of different doses of vitamin E or vitamin C in rats. The rats were supplemented with different doses of vitamin C or vitamin E for eight months. Vitamin C and vitamin E increased fasting blood glucose, insulin, and homeostasis model assessment index for insulin resistance (HOMA). Vitamin C disrupted glucose tolerance by attenuating upstream hepatic insulin action through impairing the phosphorylation and activation of insulin receptor and its subsequent substrates; however, vitamin E showed its effect downstream insulin receptor in the insulin signaling pathway, reducing hepatic glucose transporter-2 (GLUT2) and phosphorylated protein kinase (p-Akt). Moreover, both vitamins showed their antioxidant capabilities [nuclear factor-erythroid-2-related factor 2 (Nrf2), total and reduced glutathione] and their negative effect on Wnt pathway [phosphorylated glycogen synthase kinase-3β (p-GSK-3β)], by altering the previously mentioned parameters, inevitably leading to severe reduction of reactive oxygen species (ROS) below the physiological levels. In conclusion, a detrimental effect of chronic antioxidant vitamins supplementation was detected; leading to insulin resistance and impaired glucose tolerance obviously through different mechanisms. Overall, these findings indicate that the conventional view that vitamins promote health benefits and delay chronic illnesses and aging should be modified or applied with caution. Copyright © 2017. Published by Elsevier Inc.

  16. Activity-based protein profiling of the hepatitis C virus replication in Huh-7 hepatoma cells using a non-directed active site probe

    Directory of Open Access Journals (Sweden)

    McKay Craig S

    2010-02-01

    Full Text Available Abstract Background Hepatitis C virus (HCV poses a growing threat to global health as it often leads to serious liver diseases and is one of the primary causes for liver transplantation. Currently, no vaccines are available to prevent HCV infection and clinical treatments have limited success. Since HCV has a small proteome, it relies on many host cell proteins to complete its life cycle. In this study, we used a non-directed phenyl sulfonate ester probe (PS4≡ to selectively target a broad range of enzyme families that show differential activity during HCV replication in Huh-7 cells. Results The PS4≡ probe successfully targeted 19 active proteins in nine distinct protein families, some that were predominantly labeled in situ compared to the in vitro labeled cell homogenate. Nine proteins revealed altered activity levels during HCV replication. Some candidates identified, such as heat shock 70 kDa protein 8 (or HSP70 cognate, have been shown to influence viral release and abundance of cellular lipid droplets. Other differentially active PS4≡ targets, such as electron transfer flavoprotein alpha, protein disulfide isomerase A5, and nuclear distribution gene C homolog, constitute novel proteins that potentially mediate HCV propagation. Conclusions These findings demonstrate the practicality and versatility of non-directed activity-based protein profiling (ABPP to complement directed methods and accelerate the discovery of altered protein activities associated with pathological states such as HCV replication. Collectively, these results highlight the ability of in situ ABPP approaches to facilitate the identification of enzymes that are either predominantly or exclusively labeled in living cells. Several of these differentially active enzymes represent possible HCV-host interactions that could be targeted for diagnostic or therapeutic purposes.

  17. How dietary arachidonic- and docosahexaenoic- acid rich oils differentially affect the murine hepatic transcriptome

    OpenAIRE

    Roberts Matthew A; Berger Alvin; Hoff Bruce

    2006-01-01

    Introduction Herein, we expand our previous work on the effects of long chain polyunsaturated fatty acids (LC-PUFA) on the murine hepatic transcriptome using novel statistical and bioinformatic approaches for evaluating microarray data. The analyses focuses on key differences in the transcriptomic response that will influence metabolism following consumption of FUNG (rich in 20:4n6), FISH (rich in 20:5n3, 22:5n3, and 22:6n3) and COMB, the combination of the two. Results Using a variance-stab...

  18. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy ( ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy ( ...

  19. Cost-effectiveness of hepatitis C treatment using generic direct-acting antivirals available in India.

    Directory of Open Access Journals (Sweden)

    Rakesh Aggarwal

    Full Text Available Availability of directly-acting antivirals (DAAs has changed the treatment landscape of hepatitis C virus (HCV infection. The high price of DAAs has restricted their use in several countries. However, in some countries such as India, generic DAAs are available at much cheaper price. This study examined whether generic DAAs could be cost-saving and how long it would take for the treatment to become cost-saving/effective.A previously-validated, mathematical model was adapted to the HCV-infected population in India to compare the outcomes of no treatment versus treatment with DAAs. Model parameters were estimated from published studies. Cost-effectiveness of HCV treatment using available DAAs was calculated, using a payer's perspective. We estimated quality-adjusted life years (QALYs, disability-adjusted life years (DALYs, total costs, and incremental cost-effectiveness ratio of DAAs versus no treatment. One-way and probabilistic sensitivity analyses were conducted.Compared with no treatment, the use of generic DAAs in Indian HCV patients would increase the life expectancy by 8.02 years, increase QALYs by 3.89, avert 19.07 DALYs, and reduce the lifetime healthcare costs by $1,309 per-person treated. Treatment became cost-effective within 2 years, and cost-saving within 10 years of its initiation overall and within 5 years in persons with cirrhosis. Treating 10,000 HCV-infected persons could prevent 3400-3850 decompensated cirrhosis, 1800-2500 HCC, and 4000-4550 liver-related deaths. The results were sensitive to the costs of DAAs, pre- and post-treatment diagnostic tests and management of cirrhosis, and quality of life after sustained virologic response.Treatment with generic DAAs available in India will improve patient outcomes, provide a good value for money within 2 years, and be ultimately cost-saving. Therefore, in this and similar settings, HCV treatment should be a priority from a public health as well an economic perspective.

  20. Hepatitis B surface antigen quantity positively correlates with plasma levels of microRNAs differentially expressed in immunological phases of chronic hepatitis B in children

    DEFF Research Database (Denmark)

    Winther, Thilde Nordmann; Heiberg, Ida Louise; Bang-Berthelsen, Claus Heiner

    2013-01-01

    Children with chronic hepatitis B (CHB) are at high risk of progressive liver disease. It is suggested that a newly-identified panel of 16 microRNAs is important in the pathogenesis of CHB in children. Subviral hepatitis B surface antigen (HBsAg) particles are produced in large excess over infect...

  1. Hepatic glycogen in humans. I. Direct formation after oral and intravenous glucose or after a 24-h fast

    International Nuclear Information System (INIS)

    Radziuk, J.

    1989-01-01

    The formation of hepatic glycogen by the direct pathway is assessed in humans after a 12-h fast and oral loading (100 g) or intravenous infusion (90 g) and after a 24-h fast and the same oral glucose load. The methodology used is based on the double tracer method. [3- 3 H]glucose is infused at a constant rate for the determination of the metabolic clearance of glucose. [1- 14 C]glucose is administered with the glucose load. One hour after absorption or the intravenous glucose infusion is terminated, a glucagon infusion is initiated to mobilize the glycogen labeled with [1- 14 C]glucose and formed during the absorptive period. At this time a third tracer, [6- 3 H]glucose, is administered to measure glucose clearance. It was found that after the 12-h fast and oral glucose loading 7.2 +/- 1.1 g of hepatic glycogen appears to be formed directly from glucose compared with 8.4 +/- 1.0 g after the same load and a 24-h fast and 8.5 +/- 0.4 g after a 12-h fast and an equivalent intravenous glucose infusion. When the amount of label ([ 14 C]glucose) mobilized that was not corrected for metabolic recycling was calculated, the data suggested that the amount of glycogen formed by gluconeogenic pathways was probably at least equal to that formed by direct uptake. It was also approximately 60% greater after a 24-h fast. It can be concluded that the amount of hepatic glycogen formed directly from glucose during glucose loading is not significantly altered by the route of entry or the extension of the fasting period to 24 h. The data suggest, however, that gluconeogenetic formation of glycogen increases with fasting

  2. Future of liver disease in the era of direct acting antivirals for the treatment of hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Francesca Romana Ponziani; Francesca Mangiola; Cecilia Binda; Maria Assunta Zocco; Massimo Siciliano; Antonio Grieco; Gian Lodovico Rapaccini; Maurizio Pompili; Antonio Gasbarrini

    2017-01-01

    Hepatitis C virus(HCV) infection has been a global health problem for decades, due to the high number of infected people and to the lack of effective and welltolerated therapies. In the last 3 years, the approval of new direct acting antivirals characterized by high rates of virological clearance and excellent tolerability has dramatically improved HCV infection curability, especially for patients with advanced liver disease and for liver transplant recipients. Long-term data about the impact of the new direct acting antivirals on liver fibrosis and liver disease-related outcomes are not yet available, due to their recent introduction. However, previously published data deriving from the use of pegylatedinterferon and ribavirin lead to hypothesizing that we are going to observe, in the future, a reduction in mortality and in the incidence of hepatocellular carcinoma, as well as a regression of fibrosis for people previously affected by hepatitis C. In the liver transplant setting, clinical improvement has already been described after treatment with the new direct acting antivirals, which has often led to patients delisting. In the future, this may hopefully reduce the gap between liver organ request and availability, probably expanding liver transplant indications to other clinical conditions. Therefore, these new drugs are going to change the natural history of HCV-related liver disease and the epidemiology of HCV infection worldwide. However, the global consequences will depend on treatment accessibility and on the number of countries that could afford the use of the new direct acting antivirals.

  3. On method of solving third-order ordinary differential equations directly using Bernstein polynomials

    Science.gov (United States)

    Khataybeh, S. N.; Hashim, I.

    2018-04-01

    In this paper, we propose for the first time a method based on Bernstein polynomials for solving directly a class of third-order ordinary differential equations (ODEs). This method gives a numerical solution by converting the equation into a system of algebraic equations which is solved directly. Some numerical examples are given to show the applicability of the method.

  4. Substance P increases liver fibrosis by differential changes in senescence of cholangiocytes and hepatic stellate cells.

    Science.gov (United States)

    Wan, Ying; Meng, Fanyin; Wu, Nan; Zhou, Tianhao; Venter, Julie; Francis, Heather; Kennedy, Lindsey; Glaser, Trenton; Bernuzzi, Francesca; Invernizzi, Pietro; Glaser, Shannon; Huang, Qiaobing; Alpini, Gianfranco

    2017-08-01

    Substance P (SP) is involved in the proliferation of cholangiocytes in bile duct-ligated (BDL) mice and human cholangiocarcinoma growth by interacting with the neurokinin-1 receptor (NK-1R). To identify whether SP regulates liver fibrosis during cholestasis, wild-type or NK-1R knockout (NK-1R -/- ) mice that received BDL or sham surgery and multidrug resistance protein 2 knockout (Mdr2 -/- ) mice treated with either an NK-1R antagonist (L-733,060) or saline were used. Additionally, wild-type mice were treated with SP or saline intraperitoneally. In vivo, there was increased expression of tachykinin precursor 1 (coding SP) and NK-1R in both BDL and Mdr2 -/- mice compared to wild-type mice. Expression of tachykinin precursor 1 and NK-1R was significantly higher in liver samples from primary sclerosing cholangitis patients compared to healthy controls. Knockout of NK-1R decreased BDL-induced liver fibrosis, and treatment with L-733,060 resulted in decreased liver fibrosis in Mdr2 -/- mice, which was shown by decreased sirius red staining, fibrosis gene and protein expression, and reduced transforming growth factor-β1 levels in serum and cholangiocyte supernatants. Furthermore, we observed that reduced liver fibrosis in NK-1R -/- mice with BDL surgery or Mdr2 -/- mice treated with L-733,060 was associated with enhanced cellular senescence of hepatic stellate cells and decreased senescence of cholangiocytes. In vitro, L-733,060 inhibited SP-induced expression of fibrotic genes in hepatic stellate cells and cholangiocytes; treatment with L-733,060 partially reversed the SP-induced decrease of senescence gene expression in cultured hepatic stellate cells and the SP-induced increase of senescence-related gene expression in cultured cholangiocytes. Collectively, our results demonstrate the regulatory effects of the SP/NK-1R axis on liver fibrosis through changes in cellular senescence during cholestatic liver injury. (Hepatology 2017;66:528-541). © 2017 by the American

  5. Access to direct-acting antivirals for the treatment of hepatitis C in a country with limited resources.

    Science.gov (United States)

    Marciano, S; Haddad, L; Borzi, S M; D'Amico, C; Gaite, L A; Aubone, M V; Sirotinsky, M E; Ratusnu, N; Frola, M S; Aparicio, M C; Ríos, B; Anselmo, M N; Hansen, R; De Filippi, S; Dans, C García; de Labra, L; Peche, M A; Strella, T M; Ibáñez Duran, M; García Rosales, M B; Dirchwolf, M; Galdame, O A; Gadano, A C

    2018-04-12

    To estimate the proportion of patients who access to direct-acting antivirals agents (DAAs) for the treatment of hepatitisC in Argentina and to evaluate factors associated with failure to access to treatment. We performed a cross-sectional study of DAAs prescriptions written by centers participating in the telemedicine project ECHO TM -Hospital Italiano of Buenos Aires between January 2016 and February 2017. A total of 143 consecutive prescriptions were evaluated; the global access was 70% (95% CI: 62%-77%). The only factor independently associated with failure to access to treatment was belonging to the public healthcare system [OR 4.98 (95% CI: 2.05- 12.09)] in comparison to belonging to private insurance or HMOs. Patients with hepatitisC who belong to the public healthcare system are 4 times more likely to fail to access to treatment of hepatitisC than patients with private insurance or other kind of insurance. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  6. Differentiation between hepatic haemangiomas and cysts with an inversion recovery single-shot turbo spin-echo (SSTSE) sequence using the TI nulling value of hepatic haemangioma with sensitivity encoding

    International Nuclear Information System (INIS)

    Katada, Yoshiaki; Nozaki, Miwako; Yasumoto, Mayumi; Ishii, Chikako; Tanaka, Hiroshi; Nakamoto, Kazuya; Ohashi, Isamu

    2010-01-01

    To evaluate the additional value of inversion recovery (IR) single-shot turbo spin-echo (SSTSE) imaging with sensitivity encoding (SENSE) using the inversion time (TI) value of hepatic haemangioma as a supplement to conventional T2-weighted turbo spin-echo (TSE) imaging for the discrimination of hepatic haemangiomas and cysts. A total of 134 lesions (77 hepatic haemangiomas, 57 hepatic cysts) in 59 patients were evaluated. Three readers evaluated these images and used a five-point scale to evaluate the lesion status. A receiver operating characteristic (ROC) analysis and 2 x 2 table analysis were used. The ROC analysis for all the readers and all the cases revealed a significantly higher area under the curve (AUC) for the combination of moderately and heavily T2-weighted TSE with IR-SSTSE images (0.945) than for moderately and heavily T2-weighted TSE images alone (0.894) (P < 0.001). For the combination of T2-weighted TSE with IR-SSTSE versus T2-weighted TSE alone, the 2 x 2 table analysis revealed a higher true-positive rate; this difference was statistically significant (P < 0.0001). The introduction of IR-SSTSE with SENSE sequences significantly improves the diagnostic accuracy of the differentiation of hepatic haemangioma and cysts while increasing the time required for routine abdominal imaging by only 20 s. (orig.)

  7. LL-37 directs macrophage differentiation toward macrophages with a proinflammatory signature.

    Science.gov (United States)

    van der Does, Anne M; Beekhuizen, Henry; Ravensbergen, Bep; Vos, Tim; Ottenhoff, Tom H M; van Dissel, Jaap T; Drijfhout, Jan W; Hiemstra, Pieter S; Nibbering, Peter H

    2010-08-01

    The human cathelicidin LL-37 has broad-spectrum antimicrobial activity. It also participates at the interface of innate and adaptive immunity by chemoattracting immune effector cells, modulating the production of a variety of inflammatory mediators by different cell types, and regulating the differentiation of monocytes into dendritic cells. In this study, we investigated the effects of LL-37 on the differentiation of human monocytes into anti-inflammatory macrophages (MPhi-2; driven by M-CSF) versus proinflammatory macrophages (MPhi-1; driven by GM-CSF) as well as on fully differentiated MPhi-1 and MPhi-2. Results revealed that monocytes cultured with M-CSF in the presence of LL-37 resulted in macrophages displaying a proinflammatory signature, namely, low expression of CD163 and little IL-10 and profound IL-12p40 production on LPS stimulation. The effects of LL-37 on M-CSF-driven macrophage differentiation were dose- and time-dependent with maximal effects observed at 10 microg/ml when the peptide was present from the start of the cultures. The peptide enhanced the GM-CSF-driven macrophage differentiation. Exposure of fully differentiated MPhi-2 to LL-37 for 6 d resulted in macrophages that produced less IL-10 and more IL-12p40 on LPS stimulation than control MPhi-2. In contrast, LL-37 had no effect on fully differentiated MPhi-1. Peptide mapping using a set of 16 overlapping 22-mer peptides covering the complete LL-37 sequence revealed that the C-terminal portion of LL-37 is responsible for directing macrophage differentiation. Our results furthermore indicate that the effects of LL-37 on macrophage differentiation required internalization of the peptide. Together, we conclude that LL-37 directs macrophage differentiation toward macrophages with a proinflammatory signature.

  8. Some New Lie Symmetry Groups of Differential-Difference Equations Obtained from a Simple Direct Method

    International Nuclear Information System (INIS)

    Zhi Hongyan

    2009-01-01

    In this paper, based on the symbolic computing system Maple, the direct method for Lie symmetry groups presented by Sen-Yue Lou [J. Phys. A: Math. Gen. 38 (2005) L129] is extended from the continuous differential equations to the differential-difference equations. With the extended method, we study the well-known differential-difference KP equation, KZ equation and (2+1)-dimensional ANNV system, and both the Lie point symmetry groups and the non-Lie symmetry groups are obtained.

  9. Bioprinting of human pluripotent stem cells and their directed differentiation into hepatocyte-like cells for the generation of mini-livers in 3D.

    Science.gov (United States)

    Faulkner-Jones, Alan; Fyfe, Catherine; Cornelissen, Dirk-Jan; Gardner, John; King, Jason; Courtney, Aidan; Shu, Wenmiao

    2015-10-21

    We report the first investigation into the bioprinting of human induced pluripotent stem cells (hiPSCs), their response to a valve-based printing process as well as their post-printing differentiation into hepatocyte-like cells (HLCs). HLCs differentiated from both hiPSCs and human embryonic stem cells (hESCs) sources were bioprinted and examined for the presence of hepatic markers to further validate the compatibility of the valve-based bioprinting process with fragile cell transfer. Examined cells were positive for nuclear factor 4 alpha and were demonstrated to secrete albumin and have morphology that was also found to be similar to that of hepatocytes. Both hESC and hiPSC lines were tested for post-printing viability and pluripotency and were found to have negligible difference in terms of viability and pluripotency between the printed and non-printed cells. hESC-derived HLCs were 3D printed using alginate hydrogel matrix and tested for viability and albumin secretion during the remaining differentiation and were found to be hepatic in nature. 3D printed with 40-layer of HLC-containing alginate structures reached peak albumin secretion at day 21 of the differentiation protocol. This work demonstrates that the valve-based printing process is gentle enough to print human pluripotent stem cells (hPSCs) (both hESCs and hiPSCs) while either maintaining their pluripotency or directing their differentiation into specific lineages. The ability to bioprint hPSCs will pave the way for producing organs or tissues on demand from patient specific cells which could be used for animal-free drug development and personalized medicine.

  10. Bioprinting of human pluripotent stem cells and their directed differentiation into hepatocyte-like cells for the generation of mini-livers in 3D

    International Nuclear Information System (INIS)

    Faulkner-Jones, Alan; Cornelissen, Dirk-Jan; Shu, Wenmiao; Fyfe, Catherine; Gardner, John; King, Jason; Courtney, Aidan

    2015-01-01

    We report the first investigation into the bioprinting of human induced pluripotent stem cells (hiPSCs), their response to a valve-based printing process as well as their post-printing differentiation into hepatocyte-like cells (HLCs). HLCs differentiated from both hiPSCs and human embryonic stem cells (hESCs) sources were bioprinted and examined for the presence of hepatic markers to further validate the compatibility of the valve-based bioprinting process with fragile cell transfer. Examined cells were positive for nuclear factor 4 alpha and were demonstrated to secrete albumin and have morphology that was also found to be similar to that of hepatocytes. Both hESC and hiPSC lines were tested for post-printing viability and pluripotency and were found to have negligible difference in terms of viability and pluripotency between the printed and non-printed cells. hESC-derived HLCs were 3D printed using alginate hydrogel matrix and tested for viability and albumin secretion during the remaining differentiation and were found to be hepatic in nature. 3D printed with 40-layer of HLC-containing alginate structures reached peak albumin secretion at day 21 of the differentiation protocol. This work demonstrates that the valve-based printing process is gentle enough to print human pluripotent stem cells (hPSCs) (both hESCs and hiPSCs) while either maintaining their pluripotency or directing their differentiation into specific lineages. The ability to bioprint hPSCs will pave the way for producing organs or tissues on demand from patient specific cells which could be used for animal-free drug development and personalized medicine. (paper)

  11. Differential effects of krill oil and fish oil on the hepatic transcriptome in mice

    Directory of Open Access Journals (Sweden)

    Lena eBurri

    2011-07-01

    Full Text Available Dietary supplementation with ω-3 polyunsaturated fatty acids (ω-3 PUFAs, specifically the fatty acids docosahexaenoic acid (DHA; 22:6 ω-3 and eicosapentaenoic acid (EPA; 20:5 ω-3, is known to have beneficial health effects including improvements in glucose and lipid homeostasis and modulation of inflammation. To evaluate the efficacy of two different sources of ω-3 PUFAs, we performed gene expression profiling in the liver of mice fed diets supplemented with either fish oil or krill oil. We found that ω-3 PUFA supplements derived from a phospholipid krill fraction (krill oil downregulated the activity of pathways involved in hepatic glucose production as well as lipid and cholesterol synthesis. The data also suggested that krill oil-supplementation increases the activity of the mitochondrial respiratory chain. Surprisingly, an equimolar dose of EPA and DHA derived from fish oil modulated fewer pathways than a krill oil-supplemented diet and did not modulate key metabolic pathways regulated by krill oil, including glucose metabolism, lipid metabolism and the mitochondrial respiratory chain. Moreover, fish oil upregulated the cholesterol synthesis pathway, which was the opposite effect of krill supplementation. Neither diet elicited changes in plasma levels of lipids, glucose or insulin, probably because the mice used in this study were young and were fed a low fat diet. Further studies of krill oil supplementation using animal models of metabolic disorders and/or diets with a higher level of fat may be required to observe these effects.

  12. How dietary arachidonic- and docosahexaenoic- acid rich oils differentially affect the murine hepatic transcriptome

    Directory of Open Access Journals (Sweden)

    Roberts Matthew A

    2006-04-01

    Full Text Available Introduction Herein, we expand our previous work on the effects of long chain polyunsaturated fatty acids (LC-PUFA on the murine hepatic transcriptome using novel statistical and bioinformatic approaches for evaluating microarray data. The analyses focuses on key differences in the transcriptomic response that will influence metabolism following consumption of FUNG (rich in 20:4n6, FISH (rich in 20:5n3, 22:5n3, and 22:6n3 and COMB, the combination of the two. Results Using a variance-stabilized F-statistic, 371 probe sets (out of 13 K probe sets in the Affymetrix Mu11K chip set were changed by dietary treatment (P Conclusion Distinct transcriptomic, signaling cascades, and predicted affects on murine liver metabolism have been elucidated for 20:4n6-rich dietary oils, 22:6n3-rich oils, and a surprisingly distinct set of genes were affected by the combination of the two. Our results emphasize that the balance of dietary n6 and n3 LC-PUFA provided for infants and in nutritional and neutraceutical applications could have profoundly different affects on metabolism and cell signaling, beyond that previously recognized.

  13. Validation of HAV biomarker 2A for differential diagnostic of hepatitis A infected and vaccinated individuals using multiplex serology.

    Science.gov (United States)

    Bohm, Katrin; Filomena, Angela; Schneiderhan-Marra, Nicole; Krause, Gérard; Sievers, Claudia

    2017-10-13

    Worldwide about 1.5 million clinical cases of hepatitis A virus (HAV) infections occur every year and increasingly countries are introducing HAV vaccination into the childhood immunization schedule with a single dose instead of the originally licenced two dose regimen. Diagnosis of acute HAV infection is determined serologically by anti-HAV-IgM detection using ELISA. Additionally anti-HAV-IgG can become positive during the early phase of symptoms, but remains detectable after infection and also after vaccination against HAV. Currently no serological marker allows the differentiation of HAV vaccinated individuals and those with a past infection with HAV. Such differentiation would greatly improve evaluation of vaccination campaigns and risk assessment of HAV outbreaks. Here we tested the HAV non-structural protein 2A, important for the capsid assembly, as a biomarker for the differentiation of the immune status in previously infected and vaccinated individuals. HAV antigens were recombinantly expressed as glutathione-S-transferase (GST) fusion proteins. Using glutathione tagged, magnetic fluorescent beads (Luminex®), the proteins were affinity purified and used in a multiplex serological assay. The multiplex HAV assay was validated using 381 reference sera in which the immune status HAV negative, vaccinated or infected was established using the Abbott ARCHITECT® HAVAb-IgM or IgG, the commercial HAV ELISA from Abnova and documentation in vaccination cards. HAV multiplex serology showed a sensitivity of 99% and specificity of 95% to detect anti-HAV IgG/IgM positive individuals. HAV biomarker 2A allowed the differentiation between previously infected and vaccinated individuals. HAV vaccinated individuals and previously infected individuals could be identified with 92% accuracy. HAV biomarker 2A can be used to differentiate between previously HAV-vaccinated and naturally infected individuals. Within a multiplex serological approach this assay can provide valuable

  14. Chromatin remodeling agent trichostatin A: a key-factor in the hepatic differentiation of human mesenchymal stem cells derived of adult bone marrow

    Directory of Open Access Journals (Sweden)

    Vinken Mathieu

    2007-04-01

    Full Text Available Abstract Background The capability of human mesenchymal stem cells (hMSC derived of adult bone marrow to undergo in vitro hepatic differentiation was investigated. Results Exposure of hMSC to a cocktail of hepatogenic factors [(fibroblast growth factor-4 (FGF-4, hepatocyte growth factor (HGF, insulin-transferrin-sodium-selenite (ITS and dexamethasone] failed to induce hepatic differentiation. Sequential exposure to these factors (FGF-4, followed by HGF, followed by HGF+ITS+dexamethasone, however, resembling the order of secretion during liver embryogenesis, induced both glycogen-storage and cytokeratin (CK18 expression. Additional exposure of the cells to trichostatin A (TSA considerably improved endodermal differentiation, as evidenced by acquisition of an epithelial morphology, chronological expression of hepatic proteins, including hepatocyte-nuclear factor (HNF-3β, alpha-fetoprotein (AFP, CK18, albumin (ALB, HNF1α, multidrug resistance-associated protein (MRP2 and CCAAT-enhancer binding protein (C/EBPα, and functional maturation, i.e. upregulated ALB secretion, urea production and inducible cytochrome P450 (CYP-dependent activity. Conclusion hMSC are able to undergo mesenchymal-to-epithelial transition. TSA is hereby essential to promote differentiation of hMSC towards functional hepatocyte-like cells.

  15. Hepatitis C in the era of direct-acting antivirals: real-world costs of untreated chronic hepatitis C; a cross-sectional study.

    LENUS (Irish Health Repository)

    Kieran, Jennifer Ann

    2015-10-26

    Recent advances in Hepatitis C therapeutics offer the possibility of cure but will be expensive. The cost of treatment may be partially offset by the avoidance of advanced liver disease. We performed a micro-costing study of the ambulatory healthcare utilisation of patients with Hepatitis C supplemented with inpatient diagnosis related group costs.

  16. Fasting exacerbates hepatic growth differentiation factor 15 to promote fatty acid β-oxidation and ketogenesis via activating XBP1 signaling in liver

    Directory of Open Access Journals (Sweden)

    Meiyuan Zhang

    2018-06-01

    Full Text Available Liver coordinates a series of metabolic adaptations to maintain systemic energy balance and provide adequate nutrients for critical organs, tissues and cells during starvation. However, the mediator(s implicated in orchestrating these fasting-induced adaptive responses and the underlying molecular mechanisms are still obscure. Here we show that hepatic growth differentiation factor 15 (GDF15 is regulated by IRE1α-XBP1s branch and promotes hepatic fatty acids β-oxidation and ketogenesis upon fasting. GDF15 expression was exacerbated in liver of mice subjected to long-term fasted or ketogenic diet feeding. Abrogation of hepatic Gdf15 dramatically attenuated hepatic β-oxidation and ketogenesis in fasted mice or mice with STZ-initiated type I diabetes. Further study revealed that XBP1s activated Gdf15 transcription via binding to its promoter. Elevated GDF15 in liver reduced lipid accumulation and impaired NALFD development in obese mice through enhancing fatty acids oxidation in liver. Therefore, our results demonstrate a novel and critical role of hepatic GDF15 activated by IRE1α-XBP1s branch in regulating adaptive responses of liver upon starvation stress. Keywords: Fasting, Fatty acid β-oxidation, Ketogenesis, GDF15, XBP1, NAFLD

  17. Metabolic syndrome in chronic hepatitis C infection: does it still matter in the era of directly acting antiviral therapy?

    Directory of Open Access Journals (Sweden)

    Lim TR

    2014-12-01

    Full Text Available TR Lim Centre for Liver Research and NIHR Biomedical Research Unit in Liver Disease, University of Birmingham and Liver and Hepatobiliary Unit, Queen Elizabeth Hospital Birmingham, UK Abstract: Metabolic syndrome is prevalent in patients with hepatitis C virus (HCV infection. Given the pandemic spread of HCV infection and metabolic syndrome, the burden of their interaction is a major public health issue. The presence of metabolic syndrome accelerates the progression of liver disease in patients with HCV infection. New drug development in HCV has seen an unprecedented rise in the last year, which resulted in better efficacy, better tolerance, and a shorter treatment duration. This review describes the underlying mechanisms and clinical effects of metabolic syndrome in HCV infection, as well as their importance in the era of new directly acting antiviral therapy. Keywords: HCV, genotype 3, metabolic syndrome, steatosis, directly acting antiviral agents

  18. Hepatitis viruses overview

    African Journals Online (AJOL)

    Hepatitis is major cause of morbidity or mortality worldwide, particularly in the developing world. The major causes of infective hepatitis are hepatitis viruses. A, B, C, D or E. In the acute phase, there are no clinical features that can reliably differentiate between these viruses. Infection may be asymptomatic or can present as.

  19. Emergence of a Stage-Dependent Human Liver Disease Signature with Directed Differentiation of Alpha-1 Antitrypsin-Deficient iPS Cells

    Directory of Open Access Journals (Sweden)

    Andrew A. Wilson

    2015-05-01

    Full Text Available Induced pluripotent stem cells (iPSCs provide an inexhaustible source of cells for modeling disease and testing drugs. Here we develop a bioinformatic approach to detect differences between the genomic programs of iPSCs derived from diseased versus normal human cohorts as they emerge during in vitro directed differentiation. Using iPSCs generated from a cohort carrying mutations (PiZZ in the gene responsible for alpha-1 antitrypsin (AAT deficiency, we find that the global transcriptomes of PiZZ iPSCs diverge from normal controls upon differentiation to hepatic cells. Expression of 135 genes distinguishes PiZZ iPSC-hepatic cells, providing potential clues to liver disease pathogenesis. The disease-specific cells display intracellular accumulation of mutant AAT protein, resulting in increased autophagic flux. Furthermore, we detect beneficial responses to the drug carbamazepine, which further augments autophagic flux, but adverse responses to known hepatotoxic drugs. Our findings support the utility of iPSCs as tools for drug development or prediction of toxicity.

  20. 1,5-Disubstituted benzimidazoles that direct cardiomyocyte differentiation from mouse embryonic stem cells.

    Science.gov (United States)

    Okolotowicz, Karl J; Bushway, Paul; Lanier, Marion; Gilley, Cynthia; Mercola, Mark; Cashman, John R

    2015-09-01

    Cardiomyopathy is the leading cause of death worldwide. Despite progress in medical treatments, heart transplantation is one of the only current options for those with infarcted heart muscle. Stem cell differentiation technology may afford cell-based therapeutics that may lead to the generation of new, healthy heart muscle cells from undifferentiated stem cells. Our approach is to use small molecules to stimulate stem cell differentiation. Herein, we describe a novel class of 1,5-disubstituted benzimidazoles that induce differentiation of stem cells into cardiac cells. We report on the evaluation in vitro for cardiomyocyte differentiation and describe structure-activity relationship results that led to molecules with drug-like properties. The results of this study show the promise of small molecules to direct stem cell lineage commitment, to probe signaling pathways and to develop compounds for the stimulation of stem cells to repair damaged heart tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. An abstract approach to some spectral problems of direct sum differential operators

    Directory of Open Access Journals (Sweden)

    Maksim S. Sokolov

    2003-07-01

    Full Text Available In this paper, we study the common spectral properties of abstract self-adjoint direct sum operators, considered in a direct sum Hilbert space. Applications of such operators arise in the modelling of processes of multi-particle quantum mechanics, quantum field theory and, specifically, in multi-interval boundary problems of differential equations. We show that a direct sum operator does not depend in a straightforward manner on the separate operators involved. That is, on having a set of self-adjoint operators giving a direct sum operator, we show how the spectral representation for this operator depends on the spectral representations for the individual operators (the coordinate operators involved in forming this sum operator. In particular it is shown that this problem is not immediately solved by taking a direct sum of the spectral properties of the coordinate operators. Primarily, these results are to be applied to operators generated by a multi-interval quasi-differential system studied, in the earlier works of Ashurov, Everitt, Gesztezy, Kirsch, Markus and Zettl. The abstract approach in this paper indicates the need for further development of spectral theory for direct sum differential operators.

  2. Consideration of Viral Resistance for Optimization of Direct Antiviral Therapy of Hepatitis C Virus Genotype 1-Infected Patients.

    Science.gov (United States)

    Dietz, Julia; Susser, Simone; Berkowski, Caterina; Perner, Dany; Zeuzem, Stefan; Sarrazin, Christoph

    2015-01-01

    Different highly effective interferon-free treatment options for chronic hepatitis C virus (HCV) infection are currently available. Pre-existence of resistance associated variants (RAVs) to direct antiviral agents (DAAs) reduces sustained virologic response (SVR) rates by 3-53% in hepatitis C virus (HCV) genotype 1 infected patients depending on different predictors and the DAA regimen used. Frequencies of single and combined resistance to NS3, NS5A and NS5B inhibitors and consequences for the applicability of different treatment regimens are unknown. Parallel population based sequencing of HCV NS3, NS5A and NS5B genes in 312 treatment-naïve Caucasian HCV genotype 1 infected patients showed the presence of major resistant variants in 20.5% (NS3), 11.9% (NS5A), and 22.1% (NS5B) with important differences for HCV subtypes. In NS3, Q80K was observed in 34.7% and 2.1% of subtype 1a and 1b patients, respectively while other RAVs to second generation protease inhibitors were detected rarely (1.4%). Within NS5A RAVs were observed in 7.1% of subtype 1a and 17.6% in subtype 1b infected patients. RAVs to non-nucleoside NS5B inhibitors were observed in 3.5% and 44.4% of subtype 1a and 1b patients, respectively. Considering all three DAA targets all subtype 1a and 98.6% of subtype 1b infected patients were wildtype for at least one interferon free DAA regimen currently available. In conclusion, baseline resistance testing allows the selection of at least one RAVs-free treatment option for nearly all patients enabling a potentially cost- and efficacy-optimized treatment of chronic hepatitis C.

  3. Consideration of Viral Resistance for Optimization of Direct Antiviral Therapy of Hepatitis C Virus Genotype 1-Infected Patients.

    Directory of Open Access Journals (Sweden)

    Julia Dietz

    Full Text Available Different highly effective interferon-free treatment options for chronic hepatitis C virus (HCV infection are currently available. Pre-existence of resistance associated variants (RAVs to direct antiviral agents (DAAs reduces sustained virologic response (SVR rates by 3-53% in hepatitis C virus (HCV genotype 1 infected patients depending on different predictors and the DAA regimen used. Frequencies of single and combined resistance to NS3, NS5A and NS5B inhibitors and consequences for the applicability of different treatment regimens are unknown. Parallel population based sequencing of HCV NS3, NS5A and NS5B genes in 312 treatment-naïve Caucasian HCV genotype 1 infected patients showed the presence of major resistant variants in 20.5% (NS3, 11.9% (NS5A, and 22.1% (NS5B with important differences for HCV subtypes. In NS3, Q80K was observed in 34.7% and 2.1% of subtype 1a and 1b patients, respectively while other RAVs to second generation protease inhibitors were detected rarely (1.4%. Within NS5A RAVs were observed in 7.1% of subtype 1a and 17.6% in subtype 1b infected patients. RAVs to non-nucleoside NS5B inhibitors were observed in 3.5% and 44.4% of subtype 1a and 1b patients, respectively. Considering all three DAA targets all subtype 1a and 98.6% of subtype 1b infected patients were wildtype for at least one interferon free DAA regimen currently available. In conclusion, baseline resistance testing allows the selection of at least one RAVs-free treatment option for nearly all patients enabling a potentially cost- and efficacy-optimized treatment of chronic hepatitis C.

  4. Minimum target prices for production of direct-acting antivirals and associated diagnostics to combat hepatitis C virus.

    Science.gov (United States)

    van de Ven, Nikolien; Fortunak, Joe; Simmons, Bryony; Ford, Nathan; Cooke, Graham S; Khoo, Saye; Hill, Andrew

    2015-04-01

    Combinations of direct-acting antivirals (DAAs) can cure hepatitis C virus (HCV) in the majority of treatment-naïve patients. Mass treatment programs to cure HCV in developing countries are only feasible if the costs of treatment and laboratory diagnostics are very low. This analysis aimed to estimate minimum costs of DAA treatment and associated diagnostic monitoring. Clinical trials of HCV DAAs were reviewed to identify combinations with consistently high rates of sustained virological response across hepatitis C genotypes. For each DAA, molecular structures, doses, treatment duration, and components of retrosynthesis were used to estimate costs of large-scale, generic production. Manufacturing costs per gram of DAA were based upon treating at least 5 million patients per year and a 40% margin for formulation. Costs of diagnostic support were estimated based on published minimum prices of genotyping, HCV antigen tests plus full blood count/clinical chemistry tests. Predicted minimum costs for 12-week courses of combination DAAs with the most consistent efficacy results were: US$122 per person for sofosbuvir+daclatasvir; US$152 for sofosbuvir+ribavirin; US$192 for sofosbuvir+ledipasvir; and US$115 for MK-8742+MK-5172. Diagnostic testing costs were estimated at US$90 for genotyping US$34 for two HCV antigen tests and US$22 for two full blood count/clinical chemistry tests. Minimum costs of treatment and diagnostics to cure hepatitis C virus infection were estimated at US$171-360 per person without genotyping or US$261-450 per person with genotyping. These cost estimates assume that existing large-scale treatment programs can be established. © 2014 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

  5. EXACT SOLITARY WAVE SOLUTIONS TO A CLASS OF NONLINEAR DIFFERENTIAL EQUATIONS USING DIRECT ALGEBRAIC METHOD

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Using direct algebraic method,exact solitary wave solutions are performed for a class of third order nonlinear dispersive disipative partial differential equations. These solutions are obtained under certain conditions for the relationship between the coefficients of the equation. The exact solitary waves of this class are rational functions of real exponentials of kink-type solutions.

  6. 16-level differential phase shift keying (D16PSK) in direct detection optical communication systems

    DEFF Research Database (Denmark)

    Sambaraju, R.; Tokle, Torger; Jensen, J.B.

    2006-01-01

    Optical 16-level differential phase shift keying (D16PSK) carrying four bits for every symbol is proposed for direct detection optical communication systems. Transmitter and receiver schematics are presented, and the receiver sensitivity is discussed. We numerically investigate the impact...

  7. Differential expression of chicken hepatic genes responsive to PFOA and PFOS

    International Nuclear Information System (INIS)

    Yeung, Leo W.Y.; Guruge, Keerthi S.; Yamanaka, Noriko; Miyazaki, Shigeru; Lam, Paul K.S.

    2007-01-01

    The effects of PFOS and PFOA on the gene expression patterns of chickens that were exposed to either PFOS or PFOA at low doses were investigated with the use of microarray techniques. Twelve Genechip Chicken Genome Arrays were used to study hepatic gene expression in 6-week-old chickens (Gallus gallus) that were exposed to either PFOA (0.1, 0.5, or 5 mg/mL), PFOS (0.02 or 0.1 mg/mL), or a saline vehicle control (0.9% NaCl in Milli-Q water) via subcutaneous implantation of a 2 mL osmotic pump for 4 weeks or for 4 weeks with a further 4 weeks of depuration. Over 240 and 480 genes were significantly affected by PFOS after 4 weeks of exposure and after 4 weeks of exposure with a further 4 weeks of depuration, respectively and over 290 and 320 genes were significantly affected by PFOA, correspondingly. For PFOS, the genes that were affected after 4 weeks of exposure were mainly related to the transport of electrons and oxygen, and the metabolism of lipids and fatty acids; while the genes that were affected after 4 weeks of exposure with a further 4 weeks of depuration were mainly related to the transport of electrons and ions, and protein amino acid phosphorylation and proteolysis. For PFOA, the genes that were affected after 4 weeks of exposure were related to the transport of ions, lipids, and electrons and cytochromes; while the genes that were affected after 4 weeks of exposure with a further 4 weeks of depuration were related to protein amino acid phosphorylation and proteolysis, the transport of ions, and the metabolism of fatty acids and lipids. The results also showed that the gene expression patterns between chickens that were treated with PFOS and those that were treated with PFOA were different, which points to the importance of the separate evaluation of the toxicities of PFOS and PFOA. Specifically, the gene expressions of CYP8B and NOV were studied

  8. Differential protein expression of hepatic cells associated with MeHg exposure: deepening into the molecular mechanisms of toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Cuello, Susana; Madrid, Yolanda; Luque-Garcia, Jose L.; Camara, Carmen [Complutense University of Madrid, Department of Analytical Chemistry, Faculty of Chemistry, Madrid (Spain); Ramos, Sonia [Institute of Food Science, Technology and Nutrition, Consejo Superior de Investigaciones Cientificas (CSIC), Madrid (Spain)

    2012-08-15

    Understanding the molecular mechanisms underlying MeHg toxicity and the way in which this molecule interacts with living organisms is a critical point since MeHg represents a well-known risk to ecosystems and human health. We used a quantitative proteomic approach based on stable isotopic labeling by amino acids in cell culture in combination with SDS-PAGE and nanoflow LC-ESI-LTQ for analyzing the differential protein expression of hepatic cells associated to MeHg exposure. Seventy-eight proteins were found de-regulated by more than 1.5-fold. We identified a number of proteins involved in different essential biological processes including apoptosis, mitochondrial dysfunction, cellular trafficking and energy production. Among these proteins, we found several molecules whose de-regulation has been already related to MeHg exposure, thus confirming the usefulness of our discovery approach, and new ones that helped to gain a deeper insight into the biomolecular mechanisms related to MeHg-induced toxicity. Overexpression of several HSPs and the proteasome 26S subunit itself showed the proteasome system as a molecular target of toxic MeHg. As for the interaction networks, the top ranked was the nucleic acid metabolism, where many of the identified de-regulated proteins are involved. (orig.)

  9. In vivo hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis

    OpenAIRE

    Zhang, Guo-Zun; Sun, Hui-Cong; Zheng, Li-Bo; Guo, Jin-Bo; Zhang, Xiao-Lan

    2017-01-01

    AIM To investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/cirrhosis. METHODS A CCl4-induced liver fibrotic/cirrhotic rat model was used to assess the effect of hUC-MSCs. Histopathology was assessed by hematoxylin and eosin (H&E), Masson trichrome and Sirius red staining. The liver biochemical profile was measured using a Beckman Coulter analyzer. Expression analysis was ...

  10. Anti-idiotypic antibodies directed against anti-HBs among the patients with chronic hepatitis B.

    Science.gov (United States)

    Kobayashi, K; Suzuki, H; Ueno, Y; Nagatomi, R; Kanno, A; Otsuki, M; Toyota, T

    1990-08-01

    Anti-idiotypic antibodies (anti-Id) against anti-HBs were found in the sera of patients with chronic hepatitis type B. Anti-idiotypic antibodies were detected by an enzyme-linked immunosorbent assay using horseradish peroxidase conjugated mouse monoclonal anti-HBs. Ten of 72 HBsAg positive sera contained anti-Id (13.9%). The prevalence of anti-Id did not appear to correlate with HBeAg/anti-HBe system. However, HB virus specific DNA polymerase activity was significantly higher in anti-Id positive sera. In the sera obtained from the patients treated with predonisolone before, anti-Id positive rate was higher than that in the patients without a history of predonisolone therapy. These results suggest that anti-Id may be related to the immunoregulatory mechanism of HB virus replication.

  11. [Direct hospitalization costs associated with chronic Hepatitis C in the Valencian Community in 2013].

    Science.gov (United States)

    Barrachina Martínez, Isabel; Giner Durán, Remedios; Vivas-Consuelo, David; López Rodado, Antonio; Maldonado Segura, José Alberto

    2018-04-23

    Hospital costs associated with Chronic Hepatitis C (HCC) arise in the final stages of the disease. Its quantification is very helpful in order to estimate and check the burden of the disease and to make financial decisions for new antivirals. The highest costs are due to the decompensation of cirrosis. Cross-sectional observational study of hospital costs of HCC diagnoses in the Valencian Community in 2013 (n= 4,486 hospital discharges). Information source: Minimum basic set of data/ Basic Minimum Data Set. The costs were considered according to the rates established for the DRG (Diagnosis related group) associated with the episodes with diagnosis of hepatitis C. The average survival of patients since the onset of the decom- pensation of their cirrhosis was estimated by a Markov model, according to the probabilities of evolution of the disease existing in Literatura. There were 4,486 hospital episodes, 1,108 due to complications of HCC, which generated 6,713 stays, readmission rate of 28.2% and mortality of 10.2%. The hospital cost amounted to 8,788,593EUR: 3,306,333EUR corresponded to Cirrhosis (5,273EUR/patient); 1,060,521EUR to Carcinoma (6,350EUR/ patient) and 2,962,873EUR to transplantation (70,544EUR/paciente. Comorbidity was 1,458,866EUR. These costs are maintai- ned for an average of 4 years once the cirrhosis decompensation begins. Cirrhosis due to HCC generates a very high hospitalization's costs. The methodology used in the estimation of these costs from the DRG can be very useful to evaluate the trend and economic impact of this disease.

  12. Direct application of Padé approximant for solving nonlinear differential equations.

    Science.gov (United States)

    Vazquez-Leal, Hector; Benhammouda, Brahim; Filobello-Nino, Uriel; Sarmiento-Reyes, Arturo; Jimenez-Fernandez, Victor Manuel; Garcia-Gervacio, Jose Luis; Huerta-Chua, Jesus; Morales-Mendoza, Luis Javier; Gonzalez-Lee, Mario

    2014-01-01

    This work presents a direct procedure to apply Padé method to find approximate solutions for nonlinear differential equations. Moreover, we present some cases study showing the strength of the method to generate highly accurate rational approximate solutions compared to other semi-analytical methods. The type of tested nonlinear equations are: a highly nonlinear boundary value problem, a differential-algebraic oscillator problem, and an asymptotic problem. The high accurate handy approximations obtained by the direct application of Padé method shows the high potential if the proposed scheme to approximate a wide variety of problems. What is more, the direct application of the Padé approximant aids to avoid the previous application of an approximative method like Taylor series method, homotopy perturbation method, Adomian Decomposition method, homotopy analysis method, variational iteration method, among others, as tools to obtain a power series solutions to post-treat with the Padé approximant. 34L30.

  13. An in vitro expansion system for generation of human iPS cell-derived hepatic progenitor-like cells exhibiting a bipotent differentiation potential.

    Directory of Open Access Journals (Sweden)

    Ayaka Yanagida

    Full Text Available Hepatoblasts, hepatic stem/progenitor cells in liver development, have a high proliferative potential and the ability to differentiate into both hepatocytes and cholangiocytes. In regenerative medicine and drug screening for the treatment of severe liver diseases, human induced pluripotent stem (iPS cell-derived mature functional hepatocytes are considered to be a potentially good cell source. However, induction of proliferation of these cells is difficult ex vivo. To circumvent this problem, we generated hepatic progenitor-like cells from human iPS cells using serial cytokine treatments in vitro. Highly proliferative hepatic progenitor-like cells were purified by fluorescence-activated cell sorting using antibodies against CD13 and CD133 that are known cell surface markers of hepatic stem/progenitor cells in fetal and adult mouse livers. When the purified CD13(highCD133(+ cells were cultured at a low density with feeder cells in the presence of suitable growth factors and signaling inhibitors (ALK inhibitor A-83-01 and ROCK inhibitor Y-27632, individual cells gave rise to relatively large colonies. These colonies consisted of two types of cells expressing hepatocytic marker genes (hepatocyte nuclear factor 4α and α-fetoprotein and a cholangiocytic marker gene (cytokeratin 7, and continued to proliferate over long periods of time. In a spheroid formation assay, these cells were found to express genes required for mature liver function, such as cytochrome P450 enzymes, and secrete albumin. When these cells were cultured in a suitable extracellular matrix gel, they eventually formed a cholangiocytic cyst-like structure with epithelial polarity, suggesting that human iPS cell-derived hepatic progenitor-like cells have a bipotent differentiation ability. Collectively these data indicate that this novel procedure using an in vitro expansion system is useful for not only liver regeneration but also for the determination of molecular mechanisms that

  14. [Value of intravoxel incoherent motion diffusion-weighted imaging in differential diagnosis of benign and malignant hepatic lesions and blood perfusion evaluation].

    Science.gov (United States)

    Ying, M L; Xiao, W W; Xu, S L; Shu, J E; Pan, J F; Fu, J F; Lu, J H; Pan, Y H; Jiang, Y

    2016-11-20

    Objective: To investigate the value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in the differential diagnosis and blood perfusion evaluation of benign and malignant hepatic lesions. Methods: A retrospective analysis was performed for 86 patients (96 lesions) with pathologically or clinically confirmed hepatic lesions or hepatic lesions diagnosed based on follow-up results, among whom 48 had malignant lesions (53 lesions) and 38 had benign lesions (43 lesions). The patients underwent conventional magnetic resonance (MR) plain scan, contrast-enhanced scan, and diffusion-weighted imaging (DWI) with different b values (b = 0, 50, 100, 150, 200, 400, 600, 800, 1 000, and 1 200 s/mm 2 ) to determine the parameters of the double exponential model for intravoxel incoherent motion (IVIM): fast diffusion coefficient Dfast, slow diffusion coefficient Dslow, and percentage of fast-diffusion constituent F value. The patients were divided into groups according to the blood supply to lesions on conventional MR plain scan and contrast-enhanced scan, and there were 47 lesions in abundant blood supply group and 49 in poor blood supply group. The data for analysis were Dfast, Dslow, and F values of benign/malignant lesion groups and abundant/poor blood supply groups. The independent samples t-test was used for statistical analysis; the independent samples non-parametric test Mann-Whitney U test was used for the comparison of F value; the receiver operating characteristic (ROC) curve was used to evaluate the value of above parameters in the differentiation of benign and malignant lesions and blood supply evaluation. Results: Compared with the malignant lesion group, the benign lesion group had significantly higher Dslow, and F values ( P benign and malignant hepatic lesions, and F value can show blood perfusion in benign and malignant hepatic lesions without the need for contrast-enhanced scan, which provides a reference for the qualitative diagnosis of liver

  15. Retinoic acid receptor signalling directly regulates osteoblast and adipocyte differentiation from mesenchymal progenitor cells

    Energy Technology Data Exchange (ETDEWEB)

    Green, A.C. [St Vincent' s Institute, Fitzroy, Victoria 3065 (Australia); Department of Medicine at St. Vincent' s Hospital, The University of Melbourne, Victoria 3065 (Australia); Kocovski, P.; Jovic, T.; Walia, M.K. [St Vincent' s Institute, Fitzroy, Victoria 3065 (Australia); Chandraratna, R.A.S. [IO Therapeutics, Inc., Santa Ana, CA 92705 (United States); Martin, T.J.; Baker, E.K. [St Vincent' s Institute, Fitzroy, Victoria 3065 (Australia); Department of Medicine at St. Vincent' s Hospital, The University of Melbourne, Victoria 3065 (Australia); Purton, L.E., E-mail: lpurton@svi.edu.au [St Vincent' s Institute, Fitzroy, Victoria 3065 (Australia); Department of Medicine at St. Vincent' s Hospital, The University of Melbourne, Victoria 3065 (Australia)

    2017-01-01

    Low and high serum retinol levels are associated with increased fracture risk and poor bone health. We recently showed retinoic acid receptors (RARs) are negative regulators of osteoclastogenesis. Here we show RARs are also negative regulators of osteoblast and adipocyte differentiation. The pan-RAR agonist, all-trans retinoic acid (ATRA), directly inhibited differentiation and mineralisation of early osteoprogenitors and impaired the differentiation of more mature osteoblast populations. In contrast, the pan-RAR antagonist, IRX4310, accelerated differentiation of early osteoprogenitors. These effects predominantly occurred via RARγ and were further enhanced by an RARα agonist or antagonist, respectively. RAR agonists similarly impaired adipogenesis in osteogenic cultures. RAR agonist treatment resulted in significant upregulation of the Wnt antagonist, Sfrp4. This accompanied reduced nuclear and cytosolic β-catenin protein and reduced expression of the Wnt target gene Axin2, suggesting impaired Wnt/β-catenin signalling. To determine the effect of RAR inhibition in post-natal mice, IRX4310 was administered to male mice for 10 days and bones were assessed by µCT. No change to trabecular bone volume was observed, however, radial bone growth was impaired. These studies show RARs directly influence osteoblast and adipocyte formation from mesenchymal cells, and inhibition of RAR signalling in vivo impairs radial bone growth in post-natal mice. - Graphical abstract: Schematic shows RAR ligand regulation of osteoblast differentiation in vitro. RARγ antagonists±RARα antagonists promote osteoblast differentiation. RARγ and RARα agonists alone or in combination block osteoblast differentiation, which correlates with upregulation of Sfrp4, and downregulation of nuclear and cytosolic β-catenin and reduced expression of the Wnt target gene Axin2. Red arrows indicate effects of RAR agonists on mediators of Wnt signalling.

  16. Differential effect of corn oil-based low trans structured fat on the plasma and hepatic lipid profile in an atherogenic mouse model: comparison to hydrogenated trans fat

    Directory of Open Access Journals (Sweden)

    Kim Hye-Jin

    2011-01-01

    Full Text Available Abstract Background Trans fat are not desirable in many aspects on health maintenance. Low trans structured fats have been reported to be relatively more safe than trans fats. Methods We examined the effects of low trans structured fat from corn oil (LC, compared with high trans fat shortening, on cholesterol and fatty acid metabolism in apo E deficient mice which is an atherogenic animal model. The animals were fed a high trans fat (10% fat: commercial shortening (CS or a low trans fat (LC diet for 12 weeks. Results LC decreased apo B and hepatic cholesterol and triglyceride concentration compared to the CS group but significantly increased plasma total cholesterol and triglyceride concentration and fecal lipids with a simultaneous increase in HDL-cholesterol level, apo A-I, and the ratio of HDL-cholesterol to total cholesterol (HTR. Reduction of hepatic lipid levels by inclusion of LC intake was observed alongside modulation of hepatic enzyme activities related to cholesterol esterification, fatty acid metabolism and fecal lipids level compared to the CS group. The differential effects of LC intake on the plasma and hepatic lipid profile seemed to be partly due to the fatty acid composition of LC which contains higher MUFA, PUFA and SFA content as well as lower content of trans fatty acids compared to CS. Conclusions We suggest that LC may exert a dual effect on plasma and hepatic lipid metabolism in an atherogenic animal model. Accordingly, LC, supplemented at 10% in diet, had an anti-atherogenic effect on these apo E-/- mice, and increased fecal lipids, decreased hepatic steatosis, but elevated plasma lipids. Further studies are needed to verify the exact mode of action regarding the complex physiological changes and alteration in lipid metabolism caused by LC.

  17. Differential effect of corn oil-based low trans structured fat on the plasma and hepatic lipid profile in an atherogenic mouse model: comparison to hydrogenated trans fat

    Science.gov (United States)

    2011-01-01

    Background Trans fat are not desirable in many aspects on health maintenance. Low trans structured fats have been reported to be relatively more safe than trans fats. Methods We examined the effects of low trans structured fat from corn oil (LC), compared with high trans fat shortening, on cholesterol and fatty acid metabolism in apo E deficient mice which is an atherogenic animal model. The animals were fed a high trans fat (10% fat: commercial shortening (CS)) or a low trans fat (LC) diet for 12 weeks. Results LC decreased apo B and hepatic cholesterol and triglyceride concentration compared to the CS group but significantly increased plasma total cholesterol and triglyceride concentration and fecal lipids with a simultaneous increase in HDL-cholesterol level, apo A-I, and the ratio of HDL-cholesterol to total cholesterol (HTR). Reduction of hepatic lipid levels by inclusion of LC intake was observed alongside modulation of hepatic enzyme activities related to cholesterol esterification, fatty acid metabolism and fecal lipids level compared to the CS group. The differential effects of LC intake on the plasma and hepatic lipid profile seemed to be partly due to the fatty acid composition of LC which contains higher MUFA, PUFA and SFA content as well as lower content of trans fatty acids compared to CS. Conclusions We suggest that LC may exert a dual effect on plasma and hepatic lipid metabolism in an atherogenic animal model. Accordingly, LC, supplemented at 10% in diet, had an anti-atherogenic effect on these apo E-/- mice, and increased fecal lipids, decreased hepatic steatosis, but elevated plasma lipids. Further studies are needed to verify the exact mode of action regarding the complex physiological changes and alteration in lipid metabolism caused by LC. PMID:21247503

  18. Direct economic burden and influencing factors in patients with hepatitis B virus related diseases in Jiangsu, China.

    Science.gov (United States)

    Zhang, Hua; Chao, Jianqian; Zhu, Liguo; Song, Long; Li, Xiyan; Liu, Pei

    2015-03-01

    The purpose of this study was to explore direct economic burden and its influencing factors in patients with hepatitis B virus (HBV) related diseases. Time phasing continuous sampling was used to select patients from August 1, 2012, to December 31, 2012, in 3 county hospitals of 3 model regions in Jiangsu Province, China. A total of 436 outpatients and 196 inpatients were observed. The average direct economic burden of HBV-associated admission was US$107.11 for outpatients, and drug fees accounted for 74%; the burden was US$3193.47 for inpatients, and the direct medical costs accounted for 96%. Multivariate linear regression analysis showed that drug fee, examination fee, and antiviral therapy were influencing factors for outpatients, while hospitalization stay, drug ratio, and patient's age were influencing factors for inpatients. It can be concluded that the direct economic burden of patients with HBV-related diseases was high compared to their household income. Measures should be taken to reduce the economic burden of patients. © 2014 APJPH.

  19. [Clinical significance of drug resistance-associated mutations in treatment of hepatitis C with direct-acting antiviral agents].

    Science.gov (United States)

    Li, Z; Chen, Z W; Ren, H; Hu, P

    2017-03-20

    Direct-acting antiviral agents (DAAs) achieve a high sustained virologic response rate in the treatment of chronic hepatitis C virus infection. However, drug resistance-associated mutations play an important role in treatment failure and have attracted more and more attention. This article elaborates on the clinical significance of drug resistance-associated mutations from the aspects of their definition, association with genotype, known drug resistance-associated mutations and their prevalence rates, the impact of drug resistance-associated mutations on treatment naive and treatment-experienced patients, and the role of clinical detection, in order to provide a reference for clinical regimens with DAAs and help to achieve higher sustained virologic response rates.

  20. Direct assessment of hepatic mitochondrial oxidative and anaplerotic fluxes in humans using dynamic 13C magnetic resonance spectroscopy

    DEFF Research Database (Denmark)

    Befroy, Douglas E; Perry, Rachel J; Jain, Nimit

    2014-01-01

    that rates of mitochondrial oxidation and anaplerosis in human liver can be directly determined noninvasively. Using this approach, we found the mean rates of hepatic tricarboxylic acid (TCA) cycle flux (VTCA) and anaplerotic flux (VANA) to be 0.43 ± 0.04 μmol g(-1) min(-1) and 0.60 ± 0.11 μmol g(-1) min(-1......), respectively, in twelve healthy, lean individuals. We also found the VANA/VTCA ratio to be 1.39 ± 0.22, which is severalfold lower than recently published estimates using an indirect approach. This method will be useful for understanding the pathogenesis of nonalcoholic fatty liver disease and type 2 diabetes...

  1. Hepatitis C

    Science.gov (United States)

    ... Workshops Follow Us Home Health Information Liver Disease Hepatitis (Viral) Hepatitis C Related Topics English English Español Section Navigation Hepatitis (Viral) What Is Viral Hepatitis? Hepatitis A Hepatitis B ...

  2. Differentiation between chronic hepatitis and normal liver of grayscale ultrasound tissue quantification using adobe photoshop(5.0)

    International Nuclear Information System (INIS)

    Choi, Jong Cheol; Oh, Jong Young; Lim, Jong Uk; Nam, Kyung Jin

    2001-01-01

    To evaluate whether was any difference in the brightness of echogenicity on gray scale ultrasound imaging between the liver with chronic hepatitis and the normal liver using Adobe photoshop 5.0 Seventy-five patients with pathologically proven chronic hepatitis and twenty normal volunteers were included in this study. Adobe photoshop 5.0 histogram was used to measure the brightness of image. The measured brightness of the liver was divided by the brightness of the kidney, and the radio was calculated and compared between patients with chronic hepatitis and the normal control groups. In addition, the degree of fibrosis was also evaluated. The difference in brightness between the normal liver and live with chronic hepatitis was statistically significant, but no statistically significant difference was observed between the brightness of the liver and the degree of fibrosis in the liver. Tissue echo quantification using Adobe Photoshop 5.0 may be a helpful diagnostic methods for the patients with chronic hepatitis.

  3. Direct costs of first-generation protease inhibitors for the treatment of genotype 1 chronic hepatitis C viral infection.

    Science.gov (United States)

    Sethi, N; Tapper, E B; Vong, A; Sethi, S; Rourke, M; Afdhal, N H

    2015-12-01

    To evaluate the cost-effectiveness of Hepatitis C therapy, robust real-world data are needed to understand the costs and benefits of treatment alternatives. The objective of this study was to evaluate the true direct cost of treatment in an unselected sequential population of patients treated at a tertiary care centre for hepatitis C virus genotype 1. A total of 200 consecutive patients were treated with interferon, ribavirin and a first-generation direct-acting antiviral agent (DAA) between 2011 and 2013. A total of 41% had cirrhosis, 31% were prior relapsers, and 41% were prior partial or null responders. Costs used were wholesale acquisition cost prices for medications, average hospital costs per day for each diagnosis code based on US inpatient hospital charges. All costs were adjusted to 2013 dollars. Sustained virologic response (SVR) was achieved in 97 patients (48.5%). A total of 14% experienced relapse, 19% breakthrough or nonresponse, and 18.5% discontinued secondary to side effects. Twenty per cent of patients had at least one hospitalization attributable to a complication of therapy. Thirty-seven per cent of patients required erythropoietin-stimulating agents, 16% received filgastrim, and 15% needed a red blood cell transfusion. The mean overall cost of treatment was $83,851 per patient. The cost per SVR was $172,889; $266,670 for patients with cirrhosis. The costs per SVR after treatment with first-generation DAAs are dependent on the stage of disease and therapy side effects. These real-world costs significantly exceed those described in prior cost-effectiveness assessments and should be used instead for future studies. © 2015 John Wiley & Sons Ltd.

  4. Direct-acting antiviral agents against hepatitis C virus and lipid metabolism.

    Science.gov (United States)

    Kanda, Tatsuo; Moriyama, Mitsuhiko

    2017-08-21

    Hepatitis C virus (HCV) infection induces steatosis and is accompanied by multiple metabolic alterations including hyperuricemia, reversible hypocholesterolemia and insulin resistance. Total cholesterol, low-density lipoprotein-cholesterol and triglyceride levels are increased by peginterferon and ribavirin combination therapy when a sustained virologic response (SVR) is achieved in patients with HCV. Steatosis is significantly more common in patients with HCV genotype 3 but interferon-free regimens are not always effective for treating HCV genotype 3 infections. HCV infection increases fatty acid synthase levels, resulting in the accumulation of fatty acids in hepatocytes. Of note, low-density lipoprotein receptor, scavenger receptor class B type I and Niemann-Pick C1-like 1 proteins are candidate receptors that may be involved in HCV. They are also required for the uptake of cholesterol from the external environment of hepatocytes. Among HCV-infected patients with or without human immunodeficiency virus infection, changes in serum lipid profiles are observed during interferon-free treatment and after the achievement of an SVR. It is evident that HCV affects cholesterol metabolism during interferon-free regimens. Although higher SVR rates were achieved with interferon-free treatment of HCV, special attention must also be paid to unexpected adverse events based on host metabolic changes including hyperlipidemia.

  5. Biomimetic hydrogels direct spinal progenitor cell differentiation and promote functional recovery after spinal cord injury

    Science.gov (United States)

    Geissler, Sydney A.; Sabin, Alexandra L.; Besser, Rachel R.; Gooden, Olivia M.; Shirk, Bryce D.; Nguyen, Quan M.; Khaing, Zin Z.; Schmidt, Christine E.

    2018-04-01

    Objective. Demyelination that results from disease or traumatic injury, such as spinal cord injury (SCI), can have a devastating effect on neural function and recovery. Many researchers are examining treatments to minimize demyelination by improving oligodendrocyte availability in vivo. Transplantation of stem and oligodendrocyte progenitor cells is a promising option, however, trials are plagued by undirected differentiation. Here we introduce a biomaterial that has been optimized to direct the differentiation of neural progenitor cells (NPCs) toward oligodendrocytes as a cell delivery vehicle after SCI. Approach. A collagen-based hydrogel was modified to mimic the mechanical properties of the neonatal spinal cord, and components present in the developing extracellular matrix were included to provide appropriate chemical cues to the NPCs to direct their differentiation toward oligodendrocytes. The hydrogel with cells was then transplanted into a unilateral cervical contusion model of SCI to examine the functional recovery with this treatment. Six behavioral tests and histological assessment were performed to examine the in vivo response to this treatment. Main results. Our results demonstrate that we can achieve a significant increase in oligodendrocyte differentiation of NPCs compared to standard culture conditions using a three-component biomaterial composed of collagen, hyaluronic acid, and laminin that has mechanical properties matched to those of neonatal neural tissue. Additionally, SCI rats with hydrogel transplants, with and without NPCs, showed functional recovery. Animals transplanted with hydrogels with NPCs showed significantly increased functional recovery over six weeks compared to the media control group. Significance. The three-component hydrogel presented here has the potential to provide cues to direct differentiation in vivo to encourage regeneration of the central nervous system.

  6. Direct Differentiation of Human Pluripotent Stem Cells into Haploid Spermatogenic Cells

    Directory of Open Access Journals (Sweden)

    Charles A. Easley, IV

    2012-09-01

    Full Text Available Human embryonic stem cells (hESCs and induced pluripotent stem cells (hiPSCs have been shown to differentiate into primordial germ cells (PGCs but not into spermatogonia, haploid spermatocytes, or spermatids. Here, we show that hESCs and hiPSCs differentiate directly into advanced male germ cell lineages, including postmeiotic, spermatid-like cells, in vitro without genetic manipulation. Furthermore, our procedure mirrors spermatogenesis in vivo by differentiating PSCs into UTF1-, PLZF-, and CDH1-positive spermatogonia-like cells; HIWI- and HILI-positive spermatocyte-like cells; and haploid cells expressing acrosin, transition protein 1, and protamine 1 (proteins that are uniquely found in spermatids and/or sperm. These spermatids show uniparental genomic imprints similar to those of human sperm on two loci: H19 and IGF2. These results demonstrate that male PSCs have the ability to differentiate directly into advanced germ cell lineages and may represent a novel strategy for studying spermatogenesis in vitro.

  7. A fuzzy logic sliding mode controlled electronic differential for a direct wheel drive EV

    Science.gov (United States)

    Ozkop, Emre; Altas, Ismail H.; Okumus, H. Ibrahim; Sharaf, Adel M.

    2015-11-01

    In this study, a direct wheel drive electric vehicle based on an electronic differential system with a fuzzy logic sliding mode controller (FLSMC) is studied. The conventional sliding surface is modified using a fuzzy rule base to obtain fuzzy dynamic sliding surfaces by changing its slopes using the global error and its derivative in a fuzzy logic inference system. The controller is compared with proportional-integral-derivative (PID) and sliding mode controllers (SMCs), which are usually preferred to be used in industry. The proposed controller provides robustness and flexibility to direct wheel drive electric vehicles. The fuzzy logic sliding mode controller, electronic differential system and the overall electrical vehicle mechanism are modelled and digitally simulated by using the Matlab software. Simulation results show that the system with FLSMC has better efficiency and performance compared to those of PID and SMCs.

  8. In Vitro and In Vivo Hepatic Differentiation of Adult Somatic Stem Cells and Extraembryonic Stem Cells for Treating End Stage Liver Diseases

    Directory of Open Access Journals (Sweden)

    Chenxia Hu

    2015-01-01

    Full Text Available The shortage of liver donors is a major handicap that prevents most patients from receiving liver transplantation and places them on a waiting list for donated liver tissue. Then, primary hepatocyte transplantation and bioartificial livers have emerged as two alternative treatments for these often fatal diseases. However, another problem has emerged. Functional hepatocytes for liver regeneration are in short supply, and they will dedifferentiate immediately in vitro after they are isolated from liver tissue. Alternative stem-cell-based therapeutic strategies, including hepatic stem cells (HSCs, embryonic stem cells (ESCs, induced pluripotent stem cells (iPSCs, and mesenchymal stem cells (MSCs, are more promising, and more attention has been devoted to these approaches because of the high potency and proliferation ability of the cells. This review will focus on the general characteristics and the progress in hepatic differentiation of adult somatic stem cells and extraembryonic stem cells in vitro and in vivo for the treatment of end stage liver diseases. The hepatic differentiation of stem cells would offer an ideal and promising source for cell therapy and tissue engineering for treating liver diseases.

  9. Rapid, Directed Differentiation of Retinal Pigment Epithelial Cells from Human Embryonic or Induced Pluripotent Stem Cells

    OpenAIRE

    Foltz, LP; Clegg, DO

    2017-01-01

    We describe a robust method to direct the differentiation of pluripotent stem cells into retinal pigment epithelial cells (RPE). The purpose of providing a detailed and thorough protocol is to clearly demonstrate each step and to make this readily available to researchers in the field. This protocol results in a homogenous layer of RPE with minimal or no manual dissection needed. The method presented here has been shown to be effective for induced pluripotent stem cells (iPSC) and human embry...

  10. Direct costs of care for hepatocellular carcinoma in patients with hepatitis C cirrhosis.

    Science.gov (United States)

    Tapper, Elliot B; Catana, Andreea M; Sethi, Nidhi; Mansuri, Daniel; Sethi, Saurabh; Vong, Annie; Afdhal, Nezam H

    2016-03-15

    Hepatitis C virus (HCV) is the commonest cause of hepatocellular carcinoma (HCC) in the United States. The benefits of HCV therapy may be measured in part by the prevention of HCC and other complications of cirrhosis. The true cost of care of the HCV patient with HCC is unknown. One hundred patients were randomly selected from a cohort of all HCC patients with HCV at a US transplant center between 2003 and 2013. Patients were categorized by the primary treatment modality, Barcelona class, and ultimate transplant status. Costs included the unit costs of procedures, imaging, hospitalizations, medications, and all subsequent care of the HCC patient until either death or the end of follow-up. Associations with survival and cost were assessed in multivariate regression models. Overall costs included a median of $176,456 (interquartile range [IQR], $84,489-$292,192) per patient or $6279 (IQR, $4043-$9720) per patient-month of observation. The median costs per patient-month were $7492 (IQR, $5137-$11,057) for transplant patients and $4830 for nontransplant patients. The highest median monthly costs were for transplant patients with Barcelona A4 disease ($11,349) and patients who received chemoembolization whether they underwent transplantation ($10,244) or not ($8853). Transarterial chemoembolization and radiofrequency ablation were independently associated with a 28% increase and a 22% decrease in costs, respectively, with adjustments for the severity of liver disease and Barcelona class. These data represent real-world estimates of the cost of HCC care provided at a transplant center and should inform economic studies of HCV therapy. © 2015 American Cancer Society.

  11. Sofosbuvir/velpatasvir en elbasvir/grazoprevir bij hepatitis C : nog meer ‘direct-acting antivirals’ – kunnen we door de bomen het bos nog wel zien?

    NARCIS (Netherlands)

    Stolk, Leo; Bruggeman, R.

    De laatste jaren is er een groot aantal ‘direct-acting antivirals’ (DAA’s) en combinatieprepaten met DAA’s voor behandeling van hepatitis C beschikbaar gekomen. De richtlijnen moeten daarom veelvuldig worden aangepast. Behandeling met combinaties van deze nieuwe DAA’s is zeer effectief en de

  12. Nuclear magnetic resonance (NMR) imaging in the diagnosis of liver disease. Differential diagnosis of hepatic tumors and correlation between NMR imaging and histological findings

    Energy Technology Data Exchange (ETDEWEB)

    Ebara, Masaaki; Oto, Masao; Sugiura, Nobuyuki; Kimura, Kunio; Okuda, Kunio; Hirooka, Noboru; Ikehira, Hiroo; Fukuda, Nobuo; Tateno, Yukio

    1984-06-01

    Characteristics of nuclear magnetic resonance (NMR) images for various liver diseases were examined using a 0.1 T resistive NMR imaging unit on 26 patients with liver disease and 10 normal volunteers. Hepatic tumors, including small hepatocellular carcinoma 1.5 cm in diameter, were detected on NMR imaging. Ring sign characteristic of nodular type hepatocellular carcinoma was shown on NMR-CT in 60 % of patients. T/sub 1/ values allowed differential diagnosis of hepatic tumors. There was close correlation between NMR images and histopathological findings. The T/sub 1/ in the liver and spleen was more prolonged in patients with liver cirrhosis than in normal volunteers, with significant differences. (Namekawa, K.).

  13. Hepatitis C virus pharmacogenomics in Latin American populations: implications in the era of direct-acting antivirals

    Directory of Open Access Journals (Sweden)

    Trinks J

    2017-03-01

    Full Text Available Julieta Trinks,1,2 Mariela Caputo,2,3 María L Hulaniuk,1 Daniel Corach,2,3 Diego Flichman2,4 1Basic Science and Experimental Medicine Institute (ICBME, University Institute of the Italian Hospital of Buenos Aires, 2Scientific and Technological National Research Council (CONICET, 3Servicio de Huellas Digitales Genéticas, Facultad de Farmacia y Bioquímica, 4Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina Abstract: In recent years, great progress has been made in the field of new therapeutic options for hepatitis C virus (HCV infection. The new direct-acting antiviral agents (DAAs represent a great hope for millions of chronically infected individuals because their use may lead to excellent cure rates with fewer side effects. In Latin America, the high prevalence of HCV genotype 1 infection and the significant association of Native American ancestry with risk predictive single-nucleotide polymorphisms (SNPs in IFNL4 and ITPA genes highlight the need to implement new treatment regimens in these populations. However, the universal accessibility to DAAs is still not a reality in the region as their high cost is one of the major, although not the only, limiting factors for their broad implementation. Therefore, under these circumstances, could the assessment of host genetic markers be a useful tool to prioritize DAA treatment until global access to these new drugs can be achieved? This review will summarize the scientific evidences and the potential implications of HCV pharmacogenomics in this rapidly evolving era of anti-HCV drug development. Keywords: hepatitis C virus, pharmacogenomics, PEG-IFN/RBV, DAAs, Latin America

  14. Construction and expression of hepatitis B surface antigen escape variants within the "a" determinant by site directed mutagenesis.

    Science.gov (United States)

    Golsaz Shirazi, Forough; Amiri, Mohammad Mehdi; Mohammadi, Hamed; Bayat, Ali Ahmad; Roohi, Azam; Khoshnoodi, Jalal; Zarnani, Amir Hassan; Jeddi-Tehrani, Mahmood; Kardar, Gholam Ali; Shokri, Fazel

    2013-09-01

    The antibody response to hepatitis B surface antigen (HBsAg) controls hepatitis B virus infection. The "a" determinant of HBsAg is the most important target for protective antibody response, diagnosis and immunoprophylaxis. Mutations in this area may induce immune escape mutants and affect the performance of HBsAg assays. To construct clinically relevant recombinant mutant forms of HBsAg and assessment of their reactivity with anti-HBs monoclonal antibodies (MAbs). Wild type (wt) and mutant (mt) HBsAg genes were constructed by site directed mutagenesis and SEOing PCR. The amplified genes were inserted into pCMV6-neo plasmid and transfected in CHO cell line. The expression of wt- and mtHBsAg was assessed by commercial ELISA assays and stable cells were established and cloned by limiting dilution. The recombinant mutants were further characterized using a panel of anti-HBs monoclonal antibodies (MAbs) and the pattern of their reactivity was assessed by ELISA. Ten HBsAg mutants having single mutation within the "a" determinant including P120E, T123N, Q129H, M133L, K141E, P142S, D144A, G145R, N146S and C147S together with a wt form were successfully constructed and expressed in CHO cells. Reactivity of anti-HBs MAbs with mtHBsAgs displayed different patterns. The effect of mutations on antibody binding differed depending on the amino acid involved and its location within the ''a'' determinant. Mutation at amino acids 123 and 145 resulted in either complete loss or significant reduction of binding to all anti-HBs MAbs. Our panel of mtHBsAgs is a valuable tool for assessment of the antibody response to HBV escape mutants and may have substantial implications in HBV immunological diagnostics.

  15. In vivo hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis.

    Science.gov (United States)

    Zhang, Guo-Zun; Sun, Hui-Cong; Zheng, Li-Bo; Guo, Jin-Bo; Zhang, Xiao-Lan

    2017-12-14

    To investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/cirrhosis. A CCl 4 -induced liver fibrotic/cirrhotic rat model was used to assess the effect of hUC-MSCs. Histopathology was assessed by hematoxylin and eosin (H&E), Masson trichrome and Sirius red staining. The liver biochemical profile was measured using a Beckman Coulter analyzer. Expression analysis was performed using immunofluorescent staining, immunohistochemistry, Western blot, and real-time PCR. We demonstrated that the infused hUC-MSCs could differentiate into hepatocytes in vivo . Functionally, the transplantation of hUC-MSCs to CCl 4 -treated rats improved liver transaminases and synthetic function, reduced liver histopathology and reversed hepatobiliary fibrosis. The reversal of hepatobiliary fibrosis was likely due to the reduced activation state of hepatic stellate cells, decreased collagen deposition, and enhanced extracellular matrix remodeling via the up-regulation of MMP-13 and down-regulation of TIMP-1. Transplanted hUC-MSCs could differentiate into functional hepatocytes that improved both the biochemical and histopathologic changes in a CCl 4 -induced rat liver fibrosis model. hUC-MSCs may offer therapeutic opportunities for treating hepatobiliary diseases, including cirrhosis.

  16. Differentiation between simple cyst and hepatic hemangioma utilizing T2-weighted magnetic resonance imaging with gradient-echo (b-FFE) technique

    International Nuclear Information System (INIS)

    Burim, Carolina Valente; D'Ippolito, Giuseppe; Pecci Neto, Luiz; Torlai, Fabiola Goda; Tiferes, Dario Ariel

    2008-01-01

    Objective: to establish the role of MRI T2-weighted sequences in the differentiation between simple cysts and hepatic hemangiomas. Materials and methods: a double-blinded, prospective, observational, cross sectional study evaluated 52 patients with 91 hepatic lesions (34 simple cysts and 57 hemangiomas) submitted to abdominal magnetic resonance imaging. The combined analysis of all sequences was considered as the golden-standard. TSE sequences with long echo trains and b-FFE sequences were subjectively analyzed by two independent observers for differentiating cysts from hemangiomas. The kappa test (κ) was utilized in the analysis of the methods accuracy and inter- and intra-observer agreement (p * ). Results: cysts and hemangiomas dimensions ranged respectively between 0.5 and 6.5 cm (mean 1.89 cm), and 0.8 and 11 cm (mean = 2.62 cm). The analysis of the sequences with long-TE and the golden-standard demonstrated a non-statistically significant agreement (k: 0.00-0.10). The agreement between the evaluation of the b-FFE sequence and the golden-standard ranged from substantial (κ: 0.62-0.71) to almost perfect (κ: 0.86) for both observers. The inter- and intra-observer agreement for the b-FFE sequence ranged from substantial (κ: 0.62-0.70) to almost perfect (κ: 0.85-0.91). Conclusion: T2-weighted images acquired with the b-FFE technique present a high accuracy and reproducibility in the differentiation between cysts and hepatic hemangiomas. (author)

  17. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Related Liver Disease Alpha-1 Antitrypsin Deficiency Autoimmune Hepatitis Benign Liver Tumors Biliary Atresia Cirrhosis of the ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of ...

  18. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice In Newborns ... are the common causes of cirrhosis? Hepatitis B & C Alcohol-related Liver Disease Non-alcoholic Fatty Liver ...

  19. [Viral hepatitis in travellers].

    Science.gov (United States)

    Abreu, Cândida

    2007-01-01

    Considering the geographical asymmetric distribution of viral hepatitis A, B and E, having a much higher prevalence in the less developed world, travellers from developed countries are exposed to a considerable and often underestimated risk of hepatitis infection. In fact a significant percentage of viral hepatitis occurring in developed countries is travel related. This results from globalization and increased mobility from tourism, international work, humanitarian and religious missions or other travel related activities. Several studies published in Europe and North America shown that more than 50% of reported cases of hepatitis A are travel related. On the other hand frequent outbreaks of hepatitis A and E in specific geographic areas raise the risk of infection in these restricted zones and that should be clearly identified. Selected aspects related with the distribution of hepatitis A, B and E are reviewed, particularly the situation in Portugal according to the published studies, as well as relevant clinical manifestations and differential diagnosis of viral hepatitis. Basic prevention rules considering enteric transmitted hepatitis (hepatitis A and hepatitis E) and parenteral transmitted (hepatitis B) are reviewed as well as hepatitis A and B immunoprophylaxis. Common clinical situations and daily practice "pre travel" advice issues are discussed according to WHO/CDC recommendations and the Portuguese National Vaccination Program. Implications from near future availability of a hepatitis E vaccine, a currently in phase 2 trial, are highlighted. Potential indications for travellers to endemic countries like India, Nepal and some regions of China, where up to 30% of sporadic cases of acute viral hepatitis are caused by hepatitis E virus, are considered. Continued epidemiological surveillance for viral hepatitis is essential to recognize and control possible outbreaks, but also to identify new viral hepatitis agents that may emerge as important global health

  20. Protective and recuperative effects of 3-bromopyruvate on immunological, hepatic and renal homeostasis in a murine host bearing ascitic lymphoma: Implication of niche dependent differential roles of macrophages.

    Science.gov (United States)

    Yadav, Saveg; Pandey, Shrish Kumar; Goel, Yugal; Kujur, Praveen Kumar; Maurya, Babu Nandan; Verma, Ashish; Kumar, Ajay; Singh, Rana Pratap; Singh, Sukh Mahendra

    2018-03-01

    3-bromopyruvate (3-BP) possesses promising antineoplastic potential, however, its effects on immunological homeostasis vis a vis hepatic and renal functions in a tumor bearing host remain unclear. Therefore, the effect of 3-BP administration to a murine host bearing a progressively growing tumor of thymoma origin, designated as Dalton's lymphoma (DL), on immunological, renal and hepatic homeostasis was investigated. Administration of 3-BP (4 mg/kg) to the tumor bearing host reversed tumor growth associated thymic atrophy and splenomegaly, accompanied by altered cell survival and repertoire of splenic, bone marrow and tumor associated macrophages (TAM). TAM displayed augmented phagocytic, tumoricidal activities and production of IL-1 and TNF-α. 3-BP-induced activation of TAM was of indirect nature, mediated by IFN-γ. Blood count of T lymphocytes (CD4 + & CD8 + ) and NK cells showed a rise in 3-BP administered tumor bearing mice. Moreover, 3-BP administration triggered modulation of immunomodulatory cytokines in serum along with refurbished hepatic and renal functions. The study indicates the role of altered cytokines balance, site specific differential macrophage functions and myelopoiesis in restoration of lymphoid organ homeostasis in 3-BP administered tumor bearing host. These observations will have long lasting impact in understanding of alternate mechanisms underlying the antitumor action of 3-BP accompanying appraisal of safety issues for optimizing its antineoplastic actions. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  1. Liver metastasis from neuroendocrine carcinoma after the use of the new direct-action antivirals against hepatitis C virus in a patient with past history of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    María Caldas

    Full Text Available The use of the new direct-action antivirals against hepatitis C virus provides very high viral eradication rates. However, various recently published articles recommend caution with their use after the appearance of some cases of de novo tumors (originated in hepatic and extra-hepatic locations and a possible shorter time period of recurrence of hepatocellular carcinomas previously treated with surgery or loco-regional therapies. The sudden drop of the number of natural killer cells secondary to the use of these new medicines has been suggested as one of the possible mechanisms responsible for this process. However, due to the controversy concerning this subject and the absence of long-term follow-up studies in clinical practice, caution is needed before definitive conclusions are settled. We present the case report of a patient diagnosed of chronic liver disease secondary to hepatitis C virus infection and a past history of hepatocellular carcinoma in complete remission after radiofrequency ablation. He was treated with the new direct-action antivirals reaching sustained viral response. Six months later, the patient was diagnosed with liver metastasis from a small-cell neuroendocrine tumor of unknown primary site.

  2. Retreatment of patients with treatment failure of direct-acting antivirals: Focus on hepatitis C virus genotype 1b.

    Science.gov (United States)

    Kanda, Tatsuo; Nirei, Kazushige; Matsumoto, Naoki; Higuchi, Teruhisa; Nakamura, Hitomi; Yamagami, Hiroaki; Matsuoka, Shunichi; Moriyama, Mitsuhiko

    2017-12-14

    The recent development of direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) infection could lead to higher sustained virological response (SVR) rates, with shorter treatment durations and fewer adverse events compared with regimens that include interferon. However, a relatively small proportion of patients cannot achieve SVR in the first treatment, including DAAs with or without peginterferon and/or ribavirin. Although retreatment with a combination of DAAs should be conducted for these patients, it is more difficult to achieve SVR when retreating these patients because of resistance-associated substitutions (RASs) or treatment-emergent substitutions. In Japan, HCV genotype 1b (GT1b) is founded in 70% of HCV-infected individuals. In this minireview, we summarize the retreatment regimens and their SVR rates for HCV GT1b. It is important to avoid drugs that target the regions targeted by initial drugs, but next-generation combinations of DAAs, such as sofosbuvir/velpatasvir/voxilaprevir for 12 wk or glecaprevir/pibrentasvir for 12 wk, are proposed to be potential solution for the HCV GT1b-infected patients with treatment failure, mainly on a basis of targeting distinctive regions. Clinicians should follow the new information and resources for DAAs and select the proper combination of DAAs for the retreatment of HCV GT1b-infected patients with treatment failure.

  3. On Direct Transformation Approach to Asymptotical Analytical Solutions of Perturbed Partial Differential Equation

    International Nuclear Information System (INIS)

    Liu Hongzhun; Pan Zuliang; Li Peng

    2006-01-01

    In this article, we will derive an equality, where the Taylor series expansion around ε = 0 for any asymptotical analytical solution of the perturbed partial differential equation (PDE) with perturbing parameter ε must be admitted. By making use of the equality, we may obtain a transformation, which directly map the analytical solutions of a given unperturbed PDE to the asymptotical analytical solutions of the corresponding perturbed one. The notion of Lie-Baecklund symmetries is introduced in order to obtain more transformations. Hence, we can directly create more transformations in virtue of known Lie-Baecklund symmetries and recursion operators of corresponding unperturbed equation. The perturbed Burgers equation and the perturbed Korteweg-de Vries (KdV) equation are used as examples.

  4. Direct numerical simulation and modeling of turbulent natural convection in a vertical differentially heated slot

    International Nuclear Information System (INIS)

    Boudjemadi, R.

    1996-03-01

    The main objectives of this thesis are the direct numerical simulation of natural convection in a vertical differentially heated slot and the improvements of second-order turbulence modelling. A three-dimensional direct numerical simulation code has been developed in order to gain a better understanding of turbulence properties in natural convection flows. This code has been validated in several physical configurations: non-stratified natural convection flows (conduction solution), stratified natural convection flows (double boundary layer solution), transitional and turbulent Poiseuille flows. For the conduction solution, the turbulent regime was reached at a Rayleigh number of 1*10 5 and 5.4*10 5 . A detailed analysis of these results has revealed the principal qualities of the available models but has also pointed our their shortcomings. This data base has been used in order to improve the triple correlations transport models and to select the turbulent time scales suitable for such flows. (author). 122 refs., figs., tabs., 4 appends

  5. Noninvasive Differentiation between Hepatic Steatosis and Steatohepatitis with MR Imaging Enhanced with USPIOs in Patients with Nonalcoholic Fatty Liver Disease: A Proof-of-Concept Study.

    Science.gov (United States)

    Smits, Loek P; Coolen, Bram F; Panno, Maria D; Runge, Jurgen H; Nijhof, Wouter H; Verheij, Joanne; Nieuwdorp, Max; Stoker, Jaap; Beuers, Ulrich H; Nederveen, Aart J; Stroes, Erik S

    2016-03-01

    To (a) study the optimal timing and dosing for ultrasmall superparamagnetic iron oxide particle (USPIO)-enhanced magnetic resonance (MR) imaging of the liver in nonalcoholic fatty liver disease, (b) evaluate whether hepatic USPIO uptake is decreased in nonalcoholic steatohepatitis (NASH), and (c) study the diagnostic accuracy of USPIO-enhanced MR imaging to distinguish between NASH and simple steatosis. This prospective study was approved by the local institutional review board, and informed consent was obtained from all patients. Quantitative R2* MR imaging of the liver was performed at baseline and 72 hours after USPIO administration in patients with biopsy-proven NASH (n = 13), hepatic steatosis without NASH (n = 11), and healthy control subjects (n = 9). The hepatic USPIO uptake in the liver was quantified by the difference in R2* (ΔR2*) between the contrast material-enhanced images and baseline images. Between-group differences in mean ΔR2* were tested with the Student t test, and diagnostic accuracy was tested by calculating the area under the receiver operating characteristic curve. Patients with NASH had a significantly lower ΔR2* 72 hours after USPIO administration when compared with patients who had simple steatosis and healthy control subjects (mean ± standard deviation for patients with NASH, 37.0 sec(-1) ± 16.1; patients with simple steatosis, 61.0 sec(-1) ± 17.3; and healthy control subjects, 72.2 sec(-1) ± 22.0; P = .006 for NASH vs simple steatosis; P steatosis was 0.87 (95% confidence interval: 0.72, 1.00). This proof-of-concept study provides clues that hepatic USPIO uptake in patients with NASH is decreased and that USPIO MR imaging can be used to differentiate NASH from simple steatosis.

  6. Enhanced antioxidant capacity of dental pulp-derived iPSC-differentiated hepatocytes and liver regeneration by injectable HGF-releasing hydrogel in fulminant hepatic failure.

    Science.gov (United States)

    Chiang, Chih-Hung; Wu, Wai-Wah; Li, Hsin-Yang; Chien, Yueh; Sun, Cho-Chin; Peng, Chi-Hsien; Lin, Alex Tong-Long; Huang, Chi-Shuan; Lai, Ying-Hsiu; Chiou, Shih-Hwa; Hung, Shuen-Iu; Chang, Yuh-Lih; Lan, Yuan-Tzu; Liu, Dean-Mo; Chien, Chian-Shiu; Huo, Teh-Ia; Lee, Shou-Dong; Wang, Chien-Ying

    2015-01-01

    Acute hepatic failure (AHF) is a severe liver injury leading to sustained damage and complications. Induced pluripotent stem cells (iPSCs) may be an alternative option for the treatment of AHF. In this study, we reprogrammed human dental pulp-derived fibroblasts into iPSCs, which exhibited pluripotency and the capacity to differentiate into tridermal lineages, including hepatocyte-like cells (iPSC-Heps). These iPSC-Heps resembled human embryonic stem cell-derived hepatocyte-like cells in gene signature and hepatic markers/functions. To improve iPSC-Heps engraftment, we next developed an injectable carboxymethyl-hexanoyl chitosan hydrogel (CHC) with sustained hepatocyte growth factor (HGF) release (HGF-CHC) and investigated the hepatoprotective activity of HGF-CHC-delivered iPSC-Heps in vitro and in an immunocompromised AHF mouse model induced by thioacetamide (TAA). Intrahepatic delivery of HGF-CHC-iPSC-Heps reduced the TAA-induced hepatic necrotic area and rescued liver function and recipient viability. Compared with PBS-delivered iPSC-Heps, the HGF-CHC-delivered iPSC-Heps exhibited higher antioxidant and antiapoptotic activities that reduced hepatic necrotic area. Importantly, these HGF-CHC-mediated responses could be abolished by administering anti-HGF neutralizing antibodies. In conclusion, our findings demonstrated that HGF mediated the enhancement of iPSC-Hep antioxidant/antiapoptotic capacities and hepatoprotection and that HGF-CHC is as an excellent vehicle for iPSC-Hep engraftment in iPSC-based therapy against AHF.

  7. Direct peritoneal resuscitation improves obesity-induced hepatic dysfunction after trauma.

    Science.gov (United States)

    Matheson, Paul J; Franklin, Glen A; Hurt, Ryan T; Downard, Cynthia D; Smith, Jason W; Garrison, Richard N

    2012-04-01

    The metabolic syndrome and associated fatty liver disease are thought to contribute to poor outcomes in trauma patients. Experimentally, obesity compromises liver blood flow. We sought to correlate the effect of obesity, injury severity, and liver dysfunction with trauma outcomes. We hypothesized that obesity-related liver dysfunction could be mitigated with the novel technique of adjunctive direct peritoneal resuscitation (DPR). This study has clinical and experimental arms. The clinical study was a case-controlled retrospective analysis of ICU trauma patients (n = 72 obese, n = 187 nonobese). The experimental study was a hemorrhagic shock model in obese rats to assess the effect of DPR on liver blood flow, liver function, and inflammatory mediators. In trauma patients, univariate and multivariate analyses demonstrated increasing mortality (p trauma outcomes regardless of injury severity. Obesity-related liver and renal dysfunction is aggravated by injury severity. In an obese rat model of resuscitated hemorrhagic shock, the addition of DPR abrogates trauma-induced liver, renal, and inflammatory responses. We conclude that the addition of DPR to the clinical resuscitation regimen will benefit the obese trauma patient. Published by Elsevier Inc.

  8. Design of experiments approach to engineer cell-secreted matrices for directing osteogenic differentiation.

    Science.gov (United States)

    Decaris, Martin L; Leach, J Kent

    2011-04-01

    The presentation of extracellular matrix (ECM) proteins provides an opportunity to instruct the phenotype and behavior of responsive cells. Decellularized cell-secreted matrix coatings (DM) represent a biomimetic culture surface that retains the complexity of the natural ECM. Microenvironmental culture conditions alter the composition of these matrices and ultimately the ability of DMs to direct cell fate. We employed a design of experiments (DOE) multivariable analysis approach to determine the effects and interactions of four variables (culture duration, cell seeding density, oxygen tension, and media supplementation) on the capacity of DMs to direct the osteogenic differentiation of human mesenchymal stem cells (hMSCs). DOE analysis revealed that matrices created with extended culture duration, ascorbate-2-phosphate supplementation, and in ambient oxygen tension exhibited significant correlations with enhanced hMSC differentiation. We validated the DOE model results using DMs predicted to have superior (DM1) or lesser (DM2) osteogenic potential for naïve hMSCs. Compared to cells on DM2, hMSCs cultured on DM1 expressed 2-fold higher osterix levels and deposited 3-fold more calcium over 3 weeks. Cells on DM1 coatings also exhibited greater proliferation and viability compared to DM2-coated substrates. This study demonstrates that DOE-based analysis is a powerful tool for optimizing engineered systems by identifying significant variables that have the greatest contribution to the target output.

  9. A comparison of human immunodeficiency virus, hepatitis C virus, hepatitis B virus, and human T-lymphotropic virus marker rates for directed versus volunteer blood donations to the American Red Cross during 2005 to 2010.

    Science.gov (United States)

    Dorsey, Kerri A; Moritz, Erin D; Steele, Whitney R; Eder, Anne F; Stramer, Susan L

    2013-06-01

    At most US blood centers, patients may still opt to choose specific donors to give blood for their anticipated transfusion needs. However, there is little evidence of improved safety with directed donation when compared to volunteer donation. The percentage of directed donations made to the American Red Cross (ARC) from 1995 to 2010 was determined. Infectious disease marker rates for human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV), and human T-lymphotropic virus (HTLV) were calculated for volunteer and directed donations made from 2005 to 2010. Odds ratios (ORs) were calculated to compare marker-positive rates of directed donations to volunteer donations. The percentage of donations from directed donors declined from 1.6% in 1995 to 0.12% in 2010. From 2005 to 2010, the ARC collected 38,894,782 volunteer and 69,869 directed donations. Rates of HIV, HCV, HBV, and HTLV for volunteer donations were 2.9, 32.2, 12.4, and 2.5 per 100,000 donations, respectively; for directed, the rates were 7.2, 93.0, 40.1, and 18.6 per 100,000. After demographics and first-time or repeat status were adjusted for, corresponding ORs of viral marker positivity in directed versus volunteer donations were not significant for HIV, HBV, or HTLV and significant for HCV (OR, 0.7; 95% confidence interval, 0.50-0.90). Directed donations have declined by 92% at the ARC since 1995, but have higher viral marker rates than volunteer donations. The difference can be explained in part by the effects of first-time or repeat status of the donors. Patients considering directed donation should be appropriately counseled about the potential risks. © 2012 American Association of Blood Banks.

  10. Differential profiles of direct and indirect modification of vector feeding behaviour by a plant virus.

    Science.gov (United States)

    He, Wen-Bo; Li, Jie; Liu, Shu-Sheng

    2015-01-08

    Plant viruses interact with their insect vectors directly and indirectly via host plants, and this tripartite interaction may produce fitness benefits to both the vectors and the viruses. Our previous studies show that the Middle East-Asia Minor 1 (MEAM1) species of the whitefly Bemisia tabaci complex improved its performance on tobacco plants infected by the Tomato yellow leaf curl China virus (TYLCCNV), which it transmits, although virus infection of the whitefly per se reduced its performance. Here, we use electrical penetration graph recording to investigate the direct and indirect effects of TYLCCNV on the feeding behaviour of MEAM1. When feeding on either cotton, a non-host of TYLCCNV, or uninfected tobacco, a host of TYLCCNV, virus-infection of the whiteflies impeded their feeding. Interestingly, when viruliferous whiteflies fed on virus-infected tobacco, their feeding activities were no longer negatively affected; instead, the virus promoted whitefly behaviour related to rapid and effective sap ingestion. Our findings show differential profiles of direct and indirect modification of vector feeding behaviour by a plant virus, and help to unravel the behavioural mechanisms underlying a mutualistic relationship between an insect vector and a plant virus that also has features reminiscent of an insect pathogen.

  11. Efficacy and Safety of Direct Acting Antivirals in Kidney Transplant Recipients with Chronic Hepatitis C Virus Infection.

    Science.gov (United States)

    Lin, Ming V; Sise, Meghan E; Pavlakis, Martha; Amundsen, Beth M; Chute, Donald; Rutherford, Anna E; Chung, Raymond T; Curry, Michael P; Hanifi, Jasmine M; Gabardi, Steve; Chandraker, Anil; Heher, Eliot C; Elias, Nahel; Riella, Leonardo V

    2016-01-01

    The prevalence of Hepatitis C Virus (HCV) infection is significantly higher in patients with end-stage renal disease compared to the general population and poses important clinical challenges in patients who undergo kidney transplantation. Historically, interferon-based treatment options have been limited by low rates of efficacy and significant side effects, including risk of precipitating rejection. Limited data exist on the use of all-oral, interferon-free direct-acting antiviral (DAA) therapies in kidney transplant recipients. In this study, we performed a retrospective chart review with prospective clinical follow-up of post-kidney transplant patients treated with DAA therapies at three major hospitals in Boston, MA. A total of 24 kidney recipients with HCV infection received all-oral DAA therapy post-transplant. Patients were predominantly male (79%) with a median age of 60 years (range 34-70 years), median creatinine of 1.2 mg/dL (0.66-1.76), and 42% had advanced fibrosis or cirrhosis. The majority had HCV genotype 1a infection (58%). All patients received full-dose sofosbuvir; it was paired with simeprevir (9 patients without and 3 patients with ribavirin), ledipasvir (7 patients without and 1 patient with ribavirin) or ribavirin alone (4 patients). The overall sustained virologic response (SVR12) was 91% (21 out of 23 patients). One patient achieved SVR4 but demised prior to SVR12 check point due to treatment unrelated cause. Two treatment failures were successfully retreated with alternative DAA regimens and achieved SVR. Both initials failures occurred in patients with advanced fibrosis or cirrhosis, with genotype 1a infection, and prior HCV treatment failure. Adverse events were reported in 11 patients (46%) and were managed clinically without discontinuation of therapy. Calcineurin inhibitor trough levels did not significantly change during therapy. In this multi-center series of patients, all-oral DAA therapy appears to be safe and effective in post

  12. Predicting Early Viral Control under Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus Using Pretreatment Immunological Markers

    Directory of Open Access Journals (Sweden)

    James A. Hutchinson

    2018-02-01

    Full Text Available Recent introduction of all-oral direct-acting antiviral (DAA treatment has revolutionized care of patients with chronic hepatitis C virus (HCV infection. Regrettably, the high cost of DAA treatment is burdensome for healthcare systems and may be prohibitive for some patients who would otherwise benefit. Understanding how patient-related factors influence individual responses to DAA treatment may lead to more efficient prescribing. In this observational study, patients with chronic HCV infection were comprehensively monitored by flow cytometry to identify pretreatment immunological variables that predicted HCV RNA negativity within 4 weeks of commencing DAA treatment. Twenty-three patients [genotype 1a (n = 10, 1b (n = 9, and 3 (n = 4] were treated with daclatasvir plus sofosbuvir (SOF (n = 15, ledipasvir plus SOF (n = 4, or ritonavir-boosted paritaprevir, ombitasvir, and dasabuvir (n = 4. DAA treatment most prominently altered the distribution of CD8+ memory T cell subsets. Knowing only pretreatment frequencies of CD3+ and naive CD8+ T cells allowed correct classification of 83% of patients as “fast” (HCV RNA-negative by 4 weeks or “slow” responders. In a prospective cohort, these parameters correctly classified 90% of patients. Slow responders exhibited higher frequencies of CD3+ T cells, CD8+ TEM cells, and CD5high CD27− CD57+ CD8+ chronically activated T cells, which is attributed to bystander hyperactivation of virus-non-specific CD8+ T cells. Taken together, non-specific, systemic CD8+ T cell activation predicted a longer time to viral clearance. This discovery allows pretreatment identification of individuals who may not require a full 12-week course of DAA therapy; in turn, this could lead to individualized prescribing and more efficient resource allocation.

  13. Type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases.

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    Rong Chen

    Full Text Available Many disease-susceptible SNPs exhibit significant disparity in ancestral and derived allele frequencies across worldwide populations. While previous studies have examined population differentiation of alleles at specific SNPs, global ethnic patterns of ensembles of disease risk alleles across human diseases are unexamined. To examine these patterns, we manually curated ethnic disease association data from 5,065 papers on human genetic studies representing 1,495 diseases, recording the precise risk alleles and their measured population frequencies and estimated effect sizes. We systematically compared the population frequencies of cross-ethnic risk alleles for each disease across 1,397 individuals from 11 HapMap populations, 1,064 individuals from 53 HGDP populations, and 49 individuals with whole-genome sequences from 10 populations. Type 2 diabetes (T2D demonstrated extreme directional differentiation of risk allele frequencies across human populations, compared with null distributions of European-frequency matched control genomic alleles and risk alleles for other diseases. Most T2D risk alleles share a consistent pattern of decreasing frequencies along human migration into East Asia. Furthermore, we show that these patterns contribute to disparities in predicted genetic risk across 1,397 HapMap individuals, T2D genetic risk being consistently higher for individuals in the African populations and lower in the Asian populations, irrespective of the ethnicity considered in the initial discovery of risk alleles. We observed a similar pattern in the distribution of T2D Genetic Risk Scores, which are associated with an increased risk of developing diabetes in the Diabetes Prevention Program cohort, for the same individuals. This disparity may be attributable to the promotion of energy storage and usage appropriate to environments and inconsistent energy intake. Our results indicate that the differential frequencies of T2D risk alleles may

  14. Direct Observation of Ultrafast Hole Injection from Lead Halide Perovskite by Differential Transient Transmission Spectroscopy.

    Science.gov (United States)

    Ishioka, Kunie; Barker, Bobby G; Yanagida, Masatoshi; Shirai, Yasuhiro; Miyano, Kenjiro

    2017-08-17

    Efficient charge separation at the interfaces of the perovskite with the carrier transport layers is crucial for perovskite solar cells to achieve high power conversion efficiency. We present a systematic experimental study on the hole injection dynamics from MAPbI 3 perovskite to three typical hole transport materials (HTMs). We extract the carrier dynamics directly related to the hole injection by employing a pump light with short absorption depth and comparing the transient transmission signals excited on the two sides of the sample. The differential transmission signals reveal the hole injections to PTAA and PEDOT:PSS to be complete within 1 and 2 ps, respectively, and that to NiO x to exhibit an additional slow process on a 40 ps time scale. The obtained injection dynamics are discussed in comparison with the device performance of the solar cells containing the same MAPbI 3 /HTM interfaces.

  15. Primary isolated hepatic tuberculosis

    International Nuclear Information System (INIS)

    Sheikh, A.S.F.; Qureshi, I.H.; Saba, K.; Bukhari, M.H.

    2013-01-01

    Isolated hepatic tuberculosis without pulmonary or bowel involvement is a diagnostic challenge and can cause considerable morbidity. A young lady from Lahore presented with fever, pain in right hypochondria, nausea and weight loss. CT scan of abdomen showed multiple small hypodense non-enhancing lesions and a heterogeneous texture of liver. Biopsy confirmed the diagnosis of hepatic tuberculosis. It was concluded a case of isolated hepatic tuberculosis without evidence of other primary sites involvement. It is important to consider tuberculosis in the differential diagnosis when suspecting lymphoproliferative or metastatic diseases in a patient with vague symptoms and abnormal hepatic texture on CT. (author)

  16. A population approach to disease management: hepatitis C direct-acting antiviral use in a large health care system.

    Science.gov (United States)

    Belperio, Pamela S; Backus, Lisa I; Ross, David; Neuhauser, Melinda M; Mole, Larry A

    2014-06-01

    The introduction of the first direct-acting antiviral agents (DAAs) for the treatment of hepatitis C virus (HCV), telaprevir and boceprevir, marked a unique event in which 2 disease-changing therapies received FDA approval at the same time. Comparative safety and effectiveness data in real-world populations upon which to make formulary decisions did not exist. To describe the implementation, measurement, and outcomes of an enduring population-based approach of surveillance of medication management for HCV. The foundation of the population approach to HCV medication management used by the Department of Veterans Affairs (VA) relied upon a basic framework of (a) providing data for effective regional and local management, (b) education and training, (c) real-time oversight and feedback from a higher organization level, and (d) prompt outcome sharing. These population-based processes spanned across the continuum of the direct-acting antiviral oversight process. We used the VA's HCV Clinical Case Registry-which includes pharmacy, laboratory, and diagnosis information for all HCV-infected veterans from all VA facilities-to assess DAA treatment eligibility, DAA uptake and timing, appropriate use of DAAs including HCV RNA monitoring and medication possession ratios (MPR), nonconcordance with guidance for adjunct erythropoiesis-stimulating agent (ESA) and granulocyte colony-stimulating factor (GCSF) use, hematologic adverse effects, discontinuation rates, and early and sustained virologic responses. Training impact was assessed via survey and change in pharmacist scope of practice. One year after FDA approval, DAAs had been prescribed at 120 of 130 VA facilities. Over 680 VA providers participated in live educational training programs including 380 pharmacists, and pharmacists with a scope of practice for HCV increased from 59 to 110 pharmacists (86%). HCV RNA futility testing improved such that only 1%-3% of veterans did not have appropriate testing compared with 15%-17% 6

  17. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice In Newborns Diseases of the Liver ... A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice In Newborns Diseases of the Liver ...

  18. Viral Hepatitis

    Science.gov (United States)

    ... Home A-Z Health Topics Viral hepatitis Viral hepatitis > A-Z Health Topics Viral hepatitis (PDF, 90 ... liver. Source: National Cancer Institute Learn more about hepatitis Watch a video. Learn who is at risk ...

  19. Hepatitis B

    Science.gov (United States)

    ... B Entire Lesson Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For Veterans and the Public Veterans ... in their blood (sometimes referred to as the hepatitis B viral load) and an unusually high level of a ...

  20. Hepatitis C virus eradication by direct antiviral agents improves glucose tolerance and reduces post-load insulin resistance in nondiabetic patients with genotype 1.

    Science.gov (United States)

    Salomone, Federico; Catania, Maurizio; Montineri, Arturo; Bertino, Gaetano; Godos, Justyna; Rizzo, Leonardo; Magrì, Giovanni; Li Volti, Giovanni

    2017-12-19

    Genotype 1 chronic hepatitis C is associated with an impairment of glucose homoeostasis, especially in the advanced stages of the disease. Glucose tolerance is an independent predictor of liver-related mortality in patients with cirrhosis because of chronic hepatitis C. However, no study has demonstrated so far weather hepatitis C virus clearance affects glucose tolerance. To this aim, we performed a prospective study assessing the effects of direct antiviral agents treatment in nondiabetic cirrhotic patients with genotypes 1a/1b and impaired glucose tolerance based on a 75-g oral glucose tolerance test. Impaired glucose tolerance was diagnosed by a 2-hour plasma glucose between 140 and 199 mg/dL. Insulin resistance was estimated by the oral glucose insulin sensitivity index, an oral glucose tolerance test-derived measure. After meeting the inclusion criteria, the study population included 32 outpatients (26/6 genotypes 1b/1a; age 62 ± 7.4 years; 18 males) with compensated Child-A cirrhosis. All patients achieved a sustained virological response following direct antiviral agents treatment. After viral eradication, we did not observe change in fasting plasma glucose (103.5 ± 7.1 vs 102.8 ± 7.2 mg/dL, P = .15) but 2-hour plasma glucose was reduced (165.2 ± 22.7 vs 138.5 ± 21.3 mg/dL, P Hepatitis C virus eradication led also to a significant reduction in HbA1c (6.1 ± 0.2% vs 5.7 ± 0.3%, P resistance as assessed by the oral glucose insulin sensitivity index (6.92 ± 1.56 vs 9.52 ± 1.39 mg/kg/min, P  .5). Our results indicate that hepatitis C virus eradication may early improve glucose tolerance in patients with hepatitis C virus-related cirrhosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Differentiation of direct and indirect socioeconomic effects on suicide attempts in South Korea.

    Science.gov (United States)

    Ki, Myung; Seong Sohn, Eui; An, Byungduck; Lim, Jiseun

    2017-12-01

    Despite the wide recognition of the inverse association between socioeconomic position (SEP) and suicidal behaviors, its underlying process and potential mediators are little known. This study investigated the pathway from SEP to suicide attempts with attention to potential mediators.From the Korean Health and Nutrition Examination Survey 2007-2013, which is a nationwide cross-sectional survey of the health and nutritional status, a total of 34,565 participants (≥30 years) were included in the analysis. To unfold the pathways linking SEP to suicide attempts, the direct and indirect effects of 3 SEP measures (educational attainment, household income, and occupational group) and 3 mediators (physical illness, mental health problems, and problematic drinking) were differentiated using structured equation model (SEM).Most of direct and indirect effects of educational attainment, household income, and occupational group on suicide attempts were significant; Nonemployment status had the largest total (β = 0.291, P suicide attempts, compared to mental health problem and problem drinking.Overall, experience of socioeconomic disadvantage increased suicide attempts independently of mental and physical problems. An extension of suicide prevention program is required for comprehensively targeting people with general problems such as physical illness and low SEP, complemented to narrowly targeting high risk group with, such as mental health problem. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  2. Differentiating neural systems mediating the acquisition versus expression of goal-directed and habitual behavioral control

    Science.gov (United States)

    Liljeholm, Mimi; Dunne, Simon; O'Doherty, John P.

    2015-01-01

    Considerable behavioral data indicates that operant actions can become habitual, as evidenced by insensitivity to changes in the action-outcome contingency and in subjective outcome values. Notably, although several studies have investigated the neural substrates of habits, none has clearly differentiated the areas of the human brain that support habit formation from those that implement habitual control. We scanned participants with fMRI as they learned and performed an operant task in which the conditional structure of the environment encouraged either goal-directed encoding of the consequences of actions, or a habit-like mapping of actions to antecedent cues. Participants were also scanned during a subsequent assessment of insensitivity to outcome devaluation. We identified dissociable roles of the cerebellum and ventral striatum, across learning and test performance, in behavioral insensitivity to outcome devaluation. We also show that the inferior parietal lobule – an area previously implicated in several aspects of goal-directed action selection, including the attribution of intent and awareness of agency – predicts sensitivity to outcome devaluation. Finally, we reveal a potential functional homology between the human subgenual cortex and rodent infralimbic cortex in the implementation of habitual control. In summary, our findings suggest a broad systems division, at the cortical and subcortical levels, between brain areas mediating the encoding and expression of action-outcome and stimulus-response associations. PMID:25892332

  3. Use of Direct-Acting Antivirals for the Treatment of Hepatitis C Virus-Associated Oral Lichen Planus: A Case Report

    Directory of Open Access Journals (Sweden)

    Kenji Misaka

    2016-10-01

    Full Text Available Hepatitis C virus (HCV is frequently associated with various extrahepatic manifestations such as autoimmune features and immune complex deposit diseases. Oral lichen planus (OLP is one of the representative extrahepatic manifestations of HCV infection. Direct-acting antivirals (DAA are highly effective and safe for the eradication of HCV. However, there is a lack of information regarding the association between HCV-associated OLP and interferon (IFN-free DAA therapy. Herein, we present the case of a 60-year-old female who was diagnosed with OLP during routine periodontal treatment by a dentist. The patient was referred for hepatitis C treatment using IFN-free DAA, which resulted in the improvement of the symptoms of OLP. This case represents the safety and efficacy of IFN-free DAAs in patients with HCV-associated OLP. However, long-term follow-up studies are required to elucidate the therapeutic effects of this therapy in these patients.

  4. Impact of hepatitis C virus polymorphisms on direct-acting antiviral treatment efficacy: Regulatory analyses and perspectives.

    Science.gov (United States)

    Harrington, Patrick R; Komatsu, Takashi E; Deming, Damon J; Donaldson, Eric F; O'Rear, Julian J; Naeger, Lisa K

    2018-06-01

    Several highly effective, interferon-free, direct-acting antiviral (DAA)-based regimens are available for the treatment of chronic hepatitis C virus (HCV) infection. Despite impressive efficacy overall, a small proportion of patients in registrational trials experienced treatment failure, which in some cases was associated with the detection of HCV resistance-associated substitutions (RASs) at baseline. In this article, we describe methods and key findings from independent regulatory analyses investigating the impact of baseline nonstructural (NS) 3 Q80K and NS5A RASs on the efficacy of current United States Food and Drug Administration (FDA)-approved regimens for patients with HCV genotype (GT) 1 or GT3 infection. These analyses focused on clinical trials that included patients who were previously naïve to the DAA class(es) in their investigational regimen and characterized the impact of baseline RASs that were enriched in the viral population as natural or transmitted polymorphisms (i.e., not drug-selected RASs). We used a consistent approach to optimize comparability of results across different DAA regimens and patient populations, including the use of a 15% sensitivity cutoff for next-generation sequencing results and standardized lists of NS5A RASs. These analyses confirmed that detection of NS3 Q80K or NS5A baseline RASs was associated with reduced treatment efficacy for multiple DAA regimens, but their impact was often minimized with the use of an intensified treatment regimen, such as a longer treatment duration and/or addition of ribavirin. We discuss the drug resistance-related considerations that contributed to pretreatment resistance testing and treatment recommendations in drug labeling for FDA-approved DAA regimens. Independent regulatory analyses confirmed that baseline HCV RASs can reduce the efficacy of certain DAA-based regimens in selected patient groups. However, highly effective treatment options are available for patients with or without

  5. Efficacy and Safety of Direct Acting Antivirals in Kidney Transplant Recipients with Chronic Hepatitis C Virus Infection.

    Directory of Open Access Journals (Sweden)

    Ming V Lin

    Full Text Available The prevalence of Hepatitis C Virus (HCV infection is significantly higher in patients with end-stage renal disease compared to the general population and poses important clinical challenges in patients who undergo kidney transplantation. Historically, interferon-based treatment options have been limited by low rates of efficacy and significant side effects, including risk of precipitating rejection. Limited data exist on the use of all-oral, interferon-free direct-acting antiviral (DAA therapies in kidney transplant recipients. In this study, we performed a retrospective chart review with prospective clinical follow-up of post-kidney transplant patients treated with DAA therapies at three major hospitals in Boston, MA. A total of 24 kidney recipients with HCV infection received all-oral DAA therapy post-transplant. Patients were predominantly male (79% with a median age of 60 years (range 34-70 years, median creatinine of 1.2 mg/dL (0.66-1.76, and 42% had advanced fibrosis or cirrhosis. The majority had HCV genotype 1a infection (58%. All patients received full-dose sofosbuvir; it was paired with simeprevir (9 patients without and 3 patients with ribavirin, ledipasvir (7 patients without and 1 patient with ribavirin or ribavirin alone (4 patients. The overall sustained virologic response (SVR12 was 91% (21 out of 23 patients. One patient achieved SVR4 but demised prior to SVR12 check point due to treatment unrelated cause. Two treatment failures were successfully retreated with alternative DAA regimens and achieved SVR. Both initials failures occurred in patients with advanced fibrosis or cirrhosis, with genotype 1a infection, and prior HCV treatment failure. Adverse events were reported in 11 patients (46% and were managed clinically without discontinuation of therapy. Calcineurin inhibitor trough levels did not significantly change during therapy. In this multi-center series of patients, all-oral DAA therapy appears to be safe and effective

  6. Transcriptome analysis of duck liver and identification of differentially expressed transcripts in response to duck hepatitis A virus genotype C infection.

    Science.gov (United States)

    Tang, Cheng; Lan, Daoliang; Zhang, Huanrong; Ma, Jing; Yue, Hua

    2013-01-01

    Duck is an economically important poultry and animal model for human viral hepatitis B. However, the molecular mechanisms underlying host-virus interaction remain unclear because of limited information on the duck genome. This study aims to characterize the duck normal liver transcriptome and to identify the differentially expressed transcripts at 24 h after duck hepatitis A virus genotype C (DHAV-C) infection using Illumina-Solexa sequencing. After removal of low-quality sequences and assembly, a total of 52,757 unigenes was obtained from the normal liver group. Further blast analysis showed that 18,918 unigenes successfully matched the known genes in the database. GO analysis revealed that 25,116 unigenes took part in 61 categories of biological processes, cellular components, and molecular functions. Among the 25 clusters of orthologous group categories (COG), the cluster for "General function prediction only" represented the largest group, followed by "Transcription" and "Replication, recombination, and repair." KEGG analysis showed that 17,628 unigenes were involved in 301 pathways. Through comparison of normal and infected transcriptome data, we identified 20 significantly differentially expressed unigenes, which were further confirmed by real-time polymerase chain reaction. Of the 20 unigenes, nine matched the known genes in the database, including three up-regulated genes (virus replicase polyprotein, LRRC3B, and PCK1) and six down-regulated genes (CRP, AICL-like 2, L1CAM, CYB26A1, CHAC1, and ADAM32). The remaining 11 novel unigenes that did not match any known genes in the database may provide a basis for the discovery of new transcripts associated with infection. This study provided a gene expression pattern for normal duck liver and for the previously unrecognized changes in gene transcription that are altered during DHAV-C infection. Our data revealed useful information for future studies on the duck genome and provided new insights into the molecular

  7. Differential Role of Cathepsins S and B In Hepatic APC-Mediated NKT Cell Activation and Cytokine Secretion.

    Science.gov (United States)

    de Mingo Pulido, Álvaro; de Gregorio, Estefanía; Chandra, Shilpi; Colell, Anna; Morales, Albert; Kronenberg, Mitchell; Marí, Montserrat

    2018-01-01

    Natural killer T (NKT) cells exhibit a specific tissue distribution, displaying the liver the highest NKT/conventional T cell ratio. Upon antigen stimulation, NKT cells secrete Th1 cytokines, including interferon γ (IFNγ), and Th2 cytokines, including IL-4 that recruit and activate other innate immune cells to exacerbate inflammatory responses in the liver. Cysteine cathepsins control hepatic inflammation by regulating κB-dependent gene expression. However, the contribution of cysteine cathepsins other than Cathepsin S to NKT cell activation has remained largely unexplored. Here we report that cysteine cathepsins, cathepsin B (CTSB) and cathepsin S (CTSS), regulate different aspects of NKT cell activation. Inhibition of CTSB or CTSS reduced hepatic NKT cell expansion in a mouse model after LPS challenge. By contrast, only CTSS inhibition reduced IFNγ and IL-4 secretion after in vivo α-GalCer administration. Accordingly, in vitro studies reveal that only CTSS was able to control α-GalCer-dependent loading in antigen-presenting cells (APCs), probably due to altered endolysosomal protein degradation. In summary, our study discloses the participation of cysteine cathepsins, CTSB and CTSS, in the activation of NKT cells in vivo and in vitro .

  8. Differential Role of Cathepsins S and B In Hepatic APC-Mediated NKT Cell Activation and Cytokine Secretion

    Directory of Open Access Journals (Sweden)

    Álvaro de Mingo Pulido

    2018-02-01

    Full Text Available Natural killer T (NKT cells exhibit a specific tissue distribution, displaying the liver the highest NKT/conventional T cell ratio. Upon antigen stimulation, NKT cells secrete Th1 cytokines, including interferon γ (IFNγ, and Th2 cytokines, including IL-4 that recruit and activate other innate immune cells to exacerbate inflammatory responses in the liver. Cysteine cathepsins control hepatic inflammation by regulating κB-dependent gene expression. However, the contribution of cysteine cathepsins other than Cathepsin S to NKT cell activation has remained largely unexplored. Here we report that cysteine cathepsins, cathepsin B (CTSB and cathepsin S (CTSS, regulate different aspects of NKT cell activation. Inhibition of CTSB or CTSS reduced hepatic NKT cell expansion in a mouse model after LPS challenge. By contrast, only CTSS inhibition reduced IFNγ and IL-4 secretion after in vivo α-GalCer administration. Accordingly, in vitro studies reveal that only CTSS was able to control α-GalCer-dependent loading in antigen-presenting cells (APCs, probably due to altered endolysosomal protein degradation. In summary, our study discloses the participation of cysteine cathepsins, CTSB and CTSS, in the activation of NKT cells in vivo and in vitro.

  9. The Australasian Hepatology Association consensus guidelines for the provision of adherence support to patients with hepatitis C on direct acting antivirals

    Directory of Open Access Journals (Sweden)

    Richmond JA

    2016-12-01

    Full Text Available Jacqueline A Richmond,1,2 Suzanne Sheppard-Law,3,4 Susan Mason,5 Sherryne L Warner6,7 1Australian Research Centre in Sex, Health and Society, La Trobe University, 2Victorian Infectious Diseases Service, The Royal Melbourne Hospital, Melbourne, VIC, 3Faculty of Health, University of Technology, 4Sydney Children’s Hospital Network, 5AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, 6Department of Gastroenterology, Monash Health, 7Department of Medicine, Monash University, Melbourne, VIC, Australia Background: Hepatitis C is a blood-borne virus primarily spread through sharing of drug-injecting equipment. Approximately 150 million people worldwide and 230,000 Australians are living with chronic hepatitis C infection. In March 2016, the Australian government began subsidizing direct acting antivirals (DAAs for the treatment of hepatitis C, which are highly effective (95% cure rate and have few side effects. However, there is limited evidence to inform the provision of adherence support to people with hepatitis C on DAAs including the level of medication adherence required to achieve a cure. Methodology: In February 2016, a steering committee comprising four authors convened an expert panel consisting of six hepatology nurses, a hepatologist, a pharmacist, a consumer with hepatitis C and treatment experience, and a consumer advocate. The expert panel focused on the following criteria: barriers and enablers to DAA adherence; assessment and monitoring of DAA adherence; components of a patient-centered approach to DAA adherence; patients that may require additional adherence support; and interventions to support DAA adherence. The resultant guidelines underwent three rounds of consultation with the expert panel, Australasian Hepatology Association (AHA members (n=12, and key stakeholders (n=7 in June 2016. Feedback was considered by the steering committee and incorporated if consensus was achieved. Results

  10. Cell-Penetrating Peptide as a Means of Directing the Differentiation of Induced-Pluripotent Stem Cells.

    Science.gov (United States)

    Kaitsuka, Taku; Tomizawa, Kazuhito

    2015-11-06

    Protein transduction using cell-penetrating peptides (CPPs) is useful for the delivery of large protein molecules, including some transcription factors. This method is safer than gene transfection methods with a viral vector because there is no risk of genomic integration of the exogenous DNA. Recently, this method was reported as a means for the induction of induced pluripotent stem (iPS) cells, directing the differentiation into specific cell types and supporting gene editing/correction. Furthermore, we developed a direct differentiation method to obtain a pancreatic lineage from mouse and human pluripotent stem cells via the protein transduction of three transcription factors, Pdx1, NeuroD, and MafA. Here, we discuss the possibility of using CPPs as a means of directing the differentiation of iPS cells and other stem cell technologies.

  11. Cell-Penetrating Peptide as a Means of Directing the Differentiation of Induced-Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Taku Kaitsuka

    2015-11-01

    Full Text Available Protein transduction using cell-penetrating peptides (CPPs is useful for the delivery of large protein molecules, including some transcription factors. This method is safer than gene transfection methods with a viral vector because there is no risk of genomic integration of the exogenous DNA. Recently, this method was reported as a means for the induction of induced pluripotent stem (iPS cells, directing the differentiation into specific cell types and supporting gene editing/correction. Furthermore, we developed a direct differentiation method to obtain a pancreatic lineage from mouse and human pluripotent stem cells via the protein transduction of three transcription factors, Pdx1, NeuroD, and MafA. Here, we discuss the possibility of using CPPs as a means of directing the differentiation of iPS cells and other stem cell technologies.

  12. Magnetic resonance imaging in chronic liver disease evaluated in relation to hepatic fibrosis

    International Nuclear Information System (INIS)

    Ohno, Akihiko; Ohta, Yasuhiko; Ohtomo, Kuni

    1990-01-01

    In 21 patients with chronic liver disease, the ratio of liver to muscle signal intensity on T 1 -weighted images was negatively correlated with the progression of hepatic fibrosis defined according to findings by laparoscopy and liver biopsy, and differentiated six patients with early chronic hepatitis from eight with liver cirrhosis. On T 2 -weighted images, the number of low intensity nodules comparable in size to regenerating nodules surrounded by connective tissues showed a positive correlation with stage. When hepatic fibrosis with no necrosis or fat infiltration was induced in rats, T 2 values were positively correlated with hepatic hydroxyproline content, though there was no such correlation for T 1 values. These results suggest that MR imaging may be useful for determining the progression of hepatic fibrosis in chronic liver disease. T 2 values may directly reflect hepatic fibrosis. (author)

  13. Differential and directional estrogenic signaling pathways induced by enterolignans and their precursors.

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    Yun Zhu

    Full Text Available Mammalian lignans or enterolignans are metabolites of plant lignans, an important category of phytochemicals. Although they are known to be associated with estrogenic activity, cell signaling pathways leading to specific cell functions, and especially the differences among lignans, have not been explored. We examined the estrogenic activity of enterolignans and their precursor plant lignans and cell signaling pathways for some cell functions, cell cycle and chemokine secretion. We used DNA microarray-based gene expression profiling in human breast cancer MCF-7 cells to examine the similarities, as well as the differences, among enterolignans, enterolactone and enterodiol, and their precursors, matairesinol, pinoresinol and sesamin. The profiles showed moderate to high levels of correlation (R values: 0.44 to 0.81 with that of estrogen (17β-estradiol or E2. Significant correlations were observed among lignans (R values: 0.77 to 0.97, and the correlations were higher for cell functions related to enzymes, signaling, proliferation and transport. All the enterolignans/precursors examined showed activation of the Erk1/2 and PI3K/Akt pathways, indicating the involvement of rapid signaling through the non-genomic estrogen signaling pathway. However, when their effects on specific cell functions, cell cycle progression and chemokine (MCP-1 secretion were examined, positive effects were observed only for enterolactone, suggesting that signals are given in certain directions at a position closer to cell functions. We hypothesized that, while estrogen signaling is initiated by the enterolignans/precursors examined, their signals are differentially and directionally modulated later in the pathways, resulting in the differences at the cell function level.

  14. H → γγ search and direct photon pair production differential cross section

    International Nuclear Information System (INIS)

    Bu, Xuebing

    2010-01-01

    At a hadron collider, diphoton (γγ) production allows detailed studies of the Standard Model (SM), as well as as searches for new phenomena, such as new heavy resonances, extra spatial dimensions or cascade decays of heavy new particles. Within the SM, continuum γγ+X production is characterized by a steeply-falling γγ mass spectrum, on top of which a heavy resonance decaying into γγ can potentially be observed. In particular, this is considered one of the most promising discovery channels for a SM Higgs boson at the LHC, despite the small branching ratio of BR (H → γγ) ∼ 0.2% for 110 Higgs -1 of the D0 Run II data, collected at the Fermilab Tevatron collider from April 2002 to December 2008. Good agreement between the data and the SM background prediction is observed. Since there is no evidence for new physics, we set 95% C.L. limits on the production cross section times the branching ratio (σ x BR(H → γγ)) relative to the SM-like Higgs prediction for different assumed Higgs masses. The observed limits (σ(limit)/σ(SM)) range from 11.9 to 35.2 for Higgs masses from 100 to 150 GeV, while the expected limits range from 17.5 to 32.0. This search is also interpreted in the context of the particular fermiophobic Higgs model. The corresponding results have reached the same sensitivity as a single LEP experiement, setting a lower limit on the fermiophobic Higgs of M h# sub f# > 102.5 GeV (M h# sub f# > 107.5 GeV expected). We are slightly below the combined LEP limit (M h# sub f# > 109.7 GeV). We also provide access to the M h# sub f# > 125 GeV region which was inaccessible at LEP. During the study, we found the major and irreducible background direct γγ (DPP) production is not well modelled by the current theoretical predictions: RESBOS, DIPHOX or PYTHIA. There is ∼20% theoretical uncertainty for the predicted values. Thus, for our Higgs search, we use the side-band fitting method to estimate DPP contribution directly from the data events

  15. Efficient Generation of Human Embryonic Stem Cell-Derived Corneal Endothelial Cells by Directed Differentiation.

    Directory of Open Access Journals (Sweden)

    Kathryn L McCabe

    Full Text Available To generate human embryonic stem cell derived corneal endothelial cells (hESC-CECs for transplantation in patients with corneal endothelial dystrophies.Feeder-free hESC-CECs were generated by a directed differentiation protocol. hESC-CECs were characterized by morphology, expression of corneal endothelial markers, and microarray analysis of gene expression.hESC-CECs were nearly identical morphologically to primary human corneal endothelial cells, expressed Zona Occludens 1 (ZO-1 and Na+/K+ATPaseα1 (ATPA1 on the apical surface in monolayer culture, and produced the key proteins of Descemet's membrane, Collagen VIIIα1 and VIIIα2 (COL8A1 and 8A2. Quantitative PCR analysis revealed expression of all corneal endothelial pump transcripts. hESC-CECs were 96% similar to primary human adult CECs by microarray analysis.hESC-CECs are morphologically similar, express corneal endothelial cell markers and express a nearly identical complement of genes compared to human adult corneal endothelial cells. hESC-CECs may be a suitable alternative to donor-derived corneal endothelium.

  16. Magnetic resonance direct thrombus imaging differentiates acute recurrent ipsilateral deep vein thrombosis from residual thrombosis.

    Science.gov (United States)

    Tan, Melanie; Mol, Gerben C; van Rooden, Cornelis J; Klok, Frederikus A; Westerbeek, Robin E; Iglesias Del Sol, Antonio; van de Ree, Marcel A; de Roos, Albert; Huisman, Menno V

    2014-07-24

    Accurate diagnostic assessment of suspected ipsilateral recurrent deep vein thrombosis (DVT) is a major clinical challenge because differentiating between acute recurrent thrombosis and residual thrombosis is difficult with compression ultrasonography (CUS). We evaluated noninvasive magnetic resonance direct thrombus imaging (MRDTI) in a prospective study of 39 patients with symptomatic recurrent ipsilateral DVT (incompressibility of a different proximal venous segment than at the prior DVT) and 42 asymptomatic patients with at least 6-month-old chronic residual thrombi and normal D-dimer levels. All patients were subjected to MRDTI. MRDTI images were judged by 2 independent radiologists blinded for the presence of acute DVT and a third in case of disagreement. The sensitivity, specificity, and interobserver reliability of MRDTI were determined. MRDTI demonstrated acute recurrent ipsilateral DVT in 37 of 39 patients and was normal in all 42 patients without symptomatic recurrent disease for a sensitivity of 95% (95% CI, 83% to 99%) and a specificity of 100% (95% CI, 92% to 100%). Interobserver agreement was excellent (κ = 0.98). MRDTI images were adequate for interpretation in 95% of the cases. MRDTI is a sensitive and reproducible method for distinguishing acute ipsilateral recurrent DVT from 6-month-old chronic residual thrombi in the leg veins. © 2014 by The American Society of Hematology.

  17. Change of direction ability test differentiates higher level and lower level soccer referees

    Science.gov (United States)

    Los, Arcos A; Grande, I; Casajús, JA

    2016-01-01

    This report examines the agility and level of acceleration capacity of Spanish soccer referees and investigates the possible differences between field referees of different categories. The speed test consisted of 3 maximum acceleration stretches of 15 metres. The change of direction ability (CODA) test used in this study was a modification of the Modified Agility Test (MAT). The study included a sample of 41 Spanish soccer field referees from the Navarre Committee of Soccer Referees divided into two groups: i) the higher level group (G1, n = 20): 2ndA, 2ndB and 3rd division referees from the Spanish National Soccer League (28.43 ± 1.39 years); and ii) the lower level group (G2, n = 21): Navarre Provincial League soccer referees (29.54 ± 1.87 years). Significant differences were found with respect to the CODA between G1 (5.72 ± 0.13 s) and G2 (6.06 ± 0.30 s), while no differences were encountered between groups in acceleration ability. No significant correlations were obtained in G1 between agility and the capacity to accelerate. Significant correlations were found between sprint and agility times in the G2 and in the total group. The results of this study showed that agility can be used as a discriminating factor for differentiating between national and regional field referees; however, no observable differences were found over the 5 and 15 m sprint tests. PMID:27274111

  18. Hepatic encephalopathy associated with hepatic lipidosis in llamas (Lama glama).

    Science.gov (United States)

    Pillitteri, C A; Craig, L E

    2013-01-01

    Hepatic encephalopathy has been listed as a differential for llamas displaying neurologic signs, but it has not been histopathologically described. This report details the neurologic histopathologic findings associated with 3 cases of hepatic lipidosis with concurrent neurologic signs and compares them to 3 cases of hepatic lipidosis in the absence of neurologic signs and 3 cases without hepatic lipidosis. Brain from all 3 llamas displaying neurologic signs contained Alzheimer type II cells, which were not detected in either subset of llamas without neurologic signs. Astrocytic immunohistochemical staining intensity for glial fibrillary acid protein was decreased in llamas with neurologic signs as compared to 2 of 3 llamas with hepatic lipidosis and without neurologic signs and to 2 of 3 llamas without hepatic lipidosis. Immunohistochemical staining for S100 did not vary between groups. These findings suggest that hepatic encephalopathy may be associated with hepatic lipidosis in llamas.

  19. Assessment of triple-phase CT findings for the differentiation of fat-deficient hepatic angiomyolipoma from hepatocellular carcinoma in non-cirrhotic liver

    International Nuclear Information System (INIS)

    Jeon, Tae Yeon; Kim, Seong Hyun; Lim, Hyo K.; Lee, Won Jae

    2010-01-01

    Background: To evaluate the triple-phase CT findings for the differentiation of fat-deficient angiomyolipoma from hepatocellular carcinoma in non-cirrhotic liver. Methods: We retrospectively reviewed contrast-enhanced triple-phase CT images of 10 patients with fat-deficient hepatic angiomyolipoma and 28 patients with 29 hepatocellular carcinomas in non-cirrhotic liver proved on histologic examination. The CT findings for the two types of tumors were compared using Fisher's exact test. Results: Early draining vein depicted on arterial or portal phases was seen in eight (80%) angiomyolipomas and two hepatocellular carcinomas (7%) (p < 0.001), in which the early draining vein was connected with tumoral vessels. The tumoral vessels in the angiomyolipoma were more prominent and ectatic, were distributed both centrally and peripherally, and were seen in smaller tumors than in the hepatocellular carcinoma. Tumor capsule enhancement was absent in all angiomyolipomas as compared with two (7%) hepatocellular carcinomas with no tumor capsule (p < 0.001). The other CT findings were not significantly different for the two different types of tumors. Conclusions: The presence of early draining vein connecting with prominent tumoral vessels and absent tumor capsule were useful CT findings for the differentiation of fat-deficient angiomyolipoma from hepatocellular carcinoma in non-cirrhotic liver.

  20. Effect of HCV Core Antigen and RNA Clearance during Therapy with Direct Acting Antivirals on Hepatic Stiffness Measured with Shear Wave Elastography in Patients with Chronic Viral Hepatitis C

    Directory of Open Access Journals (Sweden)

    Mariusz Łucejko

    2018-01-01

    Full Text Available To assess a combination of novel measures of therapeutic success in the treatment of chronic hepatitis C (CHC infection, we evaluated liver stiffness (LS with shear wave elastography and hepatitis C virus core antigen (HCVcAg concentrations. We followed 34 patients during and after treatment with direct acting antivirals. All patients achieved a sustained virologic and serologic response and a significant increase of albumin levels. Decreases of alanine aminotransferase (ALT activity and alpha-fetoprotein (AFP level were observed during the treatment and follow-up period. A significant decrease in LS was observed between baseline, end of treatment (EOT, and at 24- and 96-week post-treatment follow-up. LS decline between EOT and 96-week follow-up (FU96 was observed in 79% of patients. Significant LS changes were seen in patients with advanced fibrosis, particularly in cirrhotics and in patients with ALT exceeding 100 IU/mL. There was a positive correlation between ALT activity and LS changes at the baseline versus FU96. A negative correlation was demonstrated between individual HCVcAg baseline concentrations and reduction of LS at the baseline versus FU96. In conclusion, we observed that LS significantly declined during and after antiviral treatment. It was accompanied by improvement in some liver function measures, and disappearance of both HCVcAg and HCV ribonucleic acid (HCV RNA.

  1. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice ... diseases. What are the common causes of cirrhosis? Hepatitis B & C Alcohol-related Liver Disease Non-alcoholic Fatty ...

  2. Prevalence of hepatitis C virus-resistant association substitutions to direct-acting antiviral agents in treatment-naïve hepatitis C genotype 1b-infected patients in western China

    Directory of Open Access Journals (Sweden)

    Li Z

    2017-10-01

    Full Text Available Zhao Li,* Zhi-wei Chen,* Hu Li, Hong Ren, Peng Hu Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China *These authors contributed equally to this work. Background: Direct-acting antivirals (DAAs against hepatitis C virus (HCV are potent and highly efficacious. However, resistance-associated substitutions (RASs relevant to DAAs can impair treatment effectiveness even at baseline. Moreover, the prevalence of baseline RASs in HCV genotype 1b-infected patients in western China is still unclear. Materials and methods: Direct sequencing of the HCV NS3, NS5A, and NS5B regions was performed in baseline serum samples of 70 DAAs treatment-naïve HCV 1b-infected patients in western China. The sequences were analyzed with MEGA version 5.05 software. Evolutionary patterns of RASs and amino-acid covariance patterns in the NS3, NS5A, and NS5B genes were analyzed by MEGA and Cytoscape (version 3.2.1, respectively.Results: The presence of at least one RAS in the NS3 region (C16S, T54S, Q80R/L, A87T, R117H, S122G, V132I, V170I was observed in 85.48% (53 of 62 of patients, RASs in the NS5A region (L28M, R30Q, Q54H, P58S/T, Q62H/R, Y93H were observed in 42.42% (28 of 66 of patients, and RASs in the NS5B region (N142S, A300T, C316N, A338V, S365A, L392I, M414L, I424V, A442T, V499A, S556G were observed in 100% (44 of 44 of patients. Evolutionary patterns of RASs and amino-acid covariance patterns for the NS3, NS5A, and NS5B genes are reported.Conclusion: The prevalence of RASs relevant to DAAs detected in the NS3, NS5A, and NS5B regions of HCV 1b from DAA treatment-naïve patients is high. Therefore, more attention should be paid to RASs associated with DAAs in the upcoming DAA-treatment era in China. Keywords: hepatitis C virus, unstructured proteins, resistance

  3. A Direct Test of the Differentiation Mechanism: REM, BCDMEM, and the Strength-Based Mirror Effect in Recognition Memory

    Science.gov (United States)

    Starns, Jeffrey J.; White, Corey N.; Ratcliff, Roger

    2010-01-01

    We explore competing explanations for the reduction in false alarm rate observed when studied items are strengthened. Some models, such as Retrieving Effectively from Memory (REM; Shiffrin & Steyvers, 1997), attribute the false alarm rate reduction to differentiation, a process in which strengthening memory traces at study directly reduces the…

  4. Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch

    NARCIS (Netherlands)

    Amsen, Derk; Antov, Andrey; Jankovic, Dragana; Sher, Alan; Radtke, Freddy; Souabni, Abdallah; Busslinger, Meinrad; McCright, Brent; Gridley, Thomas; Flavell, Richard A.

    2007-01-01

    CD4(+) T helper cells differentiate into T helper 1 (Th1) or Th2 effector lineages, which orchestrate immunity to different types of microbes. Both Th1 and Th2 differentiation can be induced by Notch, but what dictates which of these programs is activated in response to Notch is not known. By using

  5. Speed-variable Switched Differential Pump System for Direct Operation of Hydraulic Cylinders

    DEFF Research Database (Denmark)

    Schmidt, Lasse; Roemer, Daniel Beck; Pedersen, Henrik Clemmensen

    2015-01-01

    differential cylinders. The main idea was here to utilize an electric rotary drive, with the shaft interconnected to two antiparallel fixed displacement gear pumps, to actuate a differential cylinder. With the design carried out such that the area ratio of the cylinder matches the displacement ratio of the two...

  6. Dynamic computed tomography in various hepatic diseases. Particular reference to detection and differential diagnosis of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Takemoto, Kazumasa

    1985-03-01

    Studied were 140 cases of hepatoma, 40 of metastatic liver tumor, 18 of hemangioma, 9 of liver cirrhosis, 10 of chronic hepatitis and 10 patients with no liver disease. The dynamic CT was obtained before, 10, 30 and 50 seconds after an intravenous bolus injection of 50 ml of 65 % meglumine diatrizoate. Normal liver parenchyma and portal vein were slightly enhanced on the arterial phase and moderately enhanced on the portal phase of the dynamic CT. There was no significant change in case of chronic hepatitis, but in case of liver cirrhosis, the liver parenchyma was less enhanced than the normal liver on the portal phase. Tumor enhancement on the arterial phase was classified into 6 patterns, namely, A : homogeneous, B : inhomogeneous, C : patchy, D : ring, E : peripheral and F : no enhancement, while time-density-change was classified into 4 types, namely, type I : the tumor was most enhanced on the arterial phase, type II : the tumor was most enhanced on the portal phase, type III : tumor enhancement increased with time, type IV : there were no significant changes with time. Hepatoma was characterized by patterns A, B and C tumor enhancement and type I time-density-change, while metastatic liver tumor featured patterns D and F tumor enhancement and hemangioma was characteristic in indicating pattern E tumor enhancement and type III time-density-change. The rate of accurate diagnosis was 92 %. Small hepatoma (less than 5 cm in diameter) could be detected by conventional CT only in 38 out of 50 cases (76 %), while dynamic CT revealed an additional 8 cases. Out of 21 cases of portal vein thrombosis, 14 cases (66.7 %) were detected by the conventional CT but dynamic CT improved the rate of detection to 92.0 %. Dynamic CT also revealed 6 cases of arterioportal shunt which could not be detected at all by conventional CT. Thus dynamic CT provides useful information and should be considered as one of the routine tests in CT examination of the liver. (J.P.N.).

  7. Differential impact of hyponatremia and hepatic encephalopathy on health-related quality of life and brain metabolite abnormalities in cirrhosis.

    Science.gov (United States)

    Ahluwalia, Vishwadeep; Wade, James B; Thacker, Leroy; Kraft, Kenneth A; Sterling, Richard K; Stravitz, R Todd; Fuchs, Michael; Bouneva, Iliana; Puri, Puneet; Luketic, Velimir; Sanyal, Arun J; Gilles, Hochong; Heuman, Douglas M; Bajaj, Jasmohan S

    2013-09-01

    Hyponatremia (HN) and hepatic encephalopathy (HE) together can impair health-related quality of life (HRQOL) and cognition in cirrhosis. We aimed at studying the effect of hyponatremia on cognition, HRQOL, and brain MR spectroscopy (MRS) independent of HE. Four cirrhotic groups (no HE/HN, HE alone, HN alone (sodium <130 mEq/L), HE+HN) underwent cognitive testing, HRQOL using Sickness Impact Profile (SIP: higher score is worse; has psychosocial and physical sub-scores) and brain MRS (myoinositol (mI) and glutamate+glutamine (Glx)), which were compared across groups. A subset underwent HRQOL testing before/after diuretic withdrawal. 82 cirrhotics (30 no HE/HN, 25 HE, 17 HE+HN, and 10 HN, MELD 12, 63% hepatitis C) were included. Cirrhotics with HN alone and without HE/HN had better cognition compared to HE groups (median abnormal tests no-HE/HN: 3, HN: 3.5, HE: 6.5, HE+HN: 7, p=0.008). Despite better cognition, HN only patients had worse HRQOL in total and psychosocial SIP while both HN groups (with/without HE) had a significantly worse physical SIP (p<0.0001, all comparisons). Brain MRS showed the lowest Glx in HN and the highest in HE groups (p<0.02). mI levels were comparably decreased in the three affected (HE, HE+HN, and HN) groups compared to no HE/HN and were associated with poor HRQOL. Six HE+HN cirrhotics underwent diuretic withdrawal which improved serum sodium and total/psychosocial SIP scores. Hyponatremic cirrhotics without HE have poor HRQOL despite better cognition than those with concomitant HE. Glx levels were lowest in HN without HE but mI was similar across affected groups. HRQOL improved after diuretic withdrawal. Hyponatremia has a complex, non-linear relationship with brain Glx and mI, cognition and HRQOL. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  8. Keratin 8/18 regulation of glucose metabolism in normal versus cancerous hepatic cells through differential modulation of hexokinase status and insulin signaling

    Energy Technology Data Exchange (ETDEWEB)

    Mathew, Jasmin; Loranger, Anne; Gilbert, Stéphane [Centre de recherche en cancérologie de l' Université Laval and Centre de recherche du CHUQ (L' Hôtel-Dieu de Québec), 9 McMahon, Québec, Qc, Canada G1R 2J6 (Canada); Faure, Robert [Département de Pédiatrie, Université Laval and Centre de recherche du CHUQ (Centre Mère-Enfant), Québec, Qc, Canada G1V 4G2 (Canada); Marceau, Normand, E-mail: normand.marceau@crhdq.ulaval.ca [Centre de recherche en cancérologie de l' Université Laval and Centre de recherche du CHUQ (L' Hôtel-Dieu de Québec), 9 McMahon, Québec, Qc, Canada G1R 2J6 (Canada)

    2013-02-15

    As differentiated cells, hepatocytes primarily metabolize glucose for ATP production through oxidative phosphorylation of glycolytic pyruvate, whereas proliferative hepatocellular carcinoma (HCC) cells undergo a metabolic shift to aerobic glycolysis despite oxygen availability. Keratins, the intermediate filament (IF) proteins of epithelial cells, are expressed as pairs in a lineage/differentiation manner. Hepatocyte and HCC (hepatoma) cell IFs are made solely of keratins 8/18 (K8/K18), thus providing models of choice to address K8/K18 IF functions in normal and cancerous epithelial cells. Here, we demonstrate distinctive increases in glucose uptake, glucose-6-phosphate formation, lactate release, and glycogen formation in K8/K18 IF-lacking hepatocytes and/or hepatoma cells versus their respective IF-containing counterparts. We also show that the K8/K18-dependent glucose uptake/G6P formation is linked to alterations in hexokinase I/II/IV content and localization at mitochondria, with little effect on GLUT1 status. In addition, we find that the insulin-stimulated glycogen formation in normal hepatocytes involves the main PI-3 kinase-dependent signaling pathway and that the K8/K18 IF loss makes them more efficient glycogen producers. In comparison, the higher insulin-dependent glycogen formation in K8/K18 IF-lacking hepatoma cells is associated with a signaling occurring through a mTOR-dependent pathway, along with an augmentation in cell proliferative activity. Together, the results uncover a key K8/K18 regulation of glucose metabolism in normal and cancerous hepatic cells through differential modulations of mitochondrial HK status and insulin-mediated signaling.

  9. Early development of de novo hepatocellular carcinoma after direct-acting agent therapy: Comparison with pegylated interferon-based therapy in chronic hepatitis C patients.

    Science.gov (United States)

    Yoo, S H; Kwon, J H; Nam, S W; Kim, H Y; Kim, C W; You, C R; Choi, S W; Cho, S H; Han, J-Y; Song, D S; Chang, U I; Yang, J M; Lee, H L; Lee, S W; Han, N I; Kim, S-H; Song, M J; Hwang, S; Sung, P S; Jang, J W; Bae, S H; Choi, J Y; Yoon, S K

    2018-04-16

    Patients with chronic hepatitis C who achieve a sustained viral response after pegylated interferon therapy have a reduced risk of hepatocellular carcinoma, but the risk after treatment with direct-acting antivirals is unclear. We compared the rates of early development of hepatocellular carcinoma after direct-acting antivirals and after pegylated interferon therapy. We retrospectively analysed 785 patients with chronic hepatitis C who had no history of hepatocellular carcinoma (211 treated with pegylated interferon, 574 with direct-acting antivirals) and were followed up for at least 24 weeks after antiviral treatment. De novo hepatocellular carcinoma developed in 6 of 574 patients receiving direct-acting antivirals and in 1 of 211 patients receiving pegylated interferon. The cumulative incidence of early hepatocellular carcinoma development did not differ between the treatment groups either for the whole cohort (1.05% vs 0.47%, P = .298) or for those patients with Child-Pugh Class A cirrhosis (3.73% vs 2.94%, P = .827). Multivariate analysis indicated that alpha-fetoprotein level >9.5 ng/mL at the time of end-of-treatment response was the only independent risk factor for early development of hepatocellular carcinoma in all patients (P hepatocellular carcinoma did not differ between patients treated with pegylated interferon and those treated with direct-acting antivirals and was associated with the serum alpha-fetoprotein level at the time of end-of-treatment response. © 2018 John Wiley & Sons Ltd.

  10. Differential expression of viral PAMP receptors mRNA in peripheral blood of patients with chronic hepatitis C infection

    Directory of Open Access Journals (Sweden)

    Riñón Marta

    2007-11-01

    Full Text Available Abstract Background Pathogen-associated molecular patterns (PAMP receptors play a key role in the early host response to viruses. In this work, we determined mRNA levels of two members of the Toll-like Receptors family, (TLR3 and TLR7 and the helicase RIG-I, all of three recognizing viral RNA products, in peripheral blood of healthy donors and hepatitis C virus (HCV patients, to observe if their transcripts are altered in this disease. Methods IFN-α, TLR3, TLR7 and RIG-I levels in peripheral blood from healthy controls (n = 18 and chronic HCV patients (n = 18 were quantified by real-time polymerase chain reaction. Results Our results show that IFN-α, TLR3, TLR7 and RIG-I mRNA levels are significantly down-regulated in patients with chronic HCV infection when compared with healthy controls. We also found that the measured levels of TLR3 and TLR7, but not RIG-I, correlated significantly with those of IFN-α Conclusion Monitoring the expression of RNA-sensing receptors like TLR3, TLR7 and RIG-I during the different clinical stages of infection could bring a new source of data about the prognosis of disease.

  11. Hypervariable region 1 differentially impacts viability of hepatitis C virus strains of genotypes 1 to 6 and impairs virus neutralization

    DEFF Research Database (Denmark)

    Prentoe, Jannick; Jensen, Tanja B; Meuleman, Philip

    2011-01-01

    Hypervariable region 1 (HVR1) of hepatitis C virus (HCV) E2 envelope glycoprotein has been implicated in virus neutralization and persistence. We deleted HVR1 from JFH1-based HCV recombinants expressing Core/E1/E2/p7/NS2 of genotypes 1 to 6, previously found to grow efficiently in human hepatoma...... genetics studies revealed adaptive envelope mutations that rescued the infectivity of 1a(ΔHVR1), 1b(ΔHVR1), 2b(ΔHVR1), and 3a(ΔHVR1) recombinants. Thus, HVR1 might have distinct functional roles for different HCV isolates. Ultracentrifugation studies showed that deletion of HVR1 did not alter HCV RNA...... density distribution, whereas infectious particle density changed from a range of 1.0 to 1.1 g/ml to a single peak at ∼1.1 g/ml, suggesting that HVR1 was critical for low-density HCV particle infectivity. Using chronic-phase HCV patient sera, we found three distinct neutralization profiles...

  12. Hypervariable region 1 differentially impacts viability of hepatitis C virus strains of genotypes 1 to 6 and impairs virus neutralization

    DEFF Research Database (Denmark)

    Prentø, Jannick Cornelius; Jensen, Tanja Bertelsen; Meuleman, Philip

    2011-01-01

    Hypervariable region 1 (HVR1) of hepatitis C virus (HCV) E2 envelope glycoprotein has been implicated in virus neutralization and persistence. We deleted HVR1 from JFH1-based HCV recombinants expressing Core/E1/E2/p7/NS2 of genotypes 1 to 6, previously found to grow efficiently in human hepatoma...... genetics studies revealed adaptive envelope mutations that rescued the infectivity of 1a(¿HVR1), 1b(¿HVR1), 2b(¿HVR1), and 3a(¿HVR1) recombinants. Thus, HVR1 might have distinct functional roles for different HCV isolates. Ultracentrifugation studies showed that deletion of HVR1 did not alter HCV RNA...... density distribution, whereas infectious particle density changed from a range of 1.0 to 1.1 g/ml to a single peak at ~1.1 g/ml, suggesting that HVR1 was critical for low-density HCV particle infectivity. Using chronic-phase HCV patient sera, we found three distinct neutralization profiles...

  13. Impact of liver fat on the differential partitioning of hepatic triacylglycerol into VLDL subclasses on high and low sugar diets.

    Science.gov (United States)

    Umpleby, A Margot; Shojaee-Moradie, Fariba; Fielding, Barbara; Li, Xuefei; Marino, Andrea; Alsini, Najlaa; Isherwood, Cheryl; Jackson, Nicola; Ahmad, Aryati; Stolinski, Michael; Lovegrove, Julie A; Johnsen, Sigurd; Jeewaka R Mendis, A S; Wright, John; Wilinska, Malgorzata E; Hovorka, Roman; Bell, Jimmy D; Thomas, E Louise; Frost, Gary S; Griffin, Bruce A

    2017-11-01

    Dietary sugars are linked to the development of non-alcoholic fatty liver disease (NAFLD) and dyslipidaemia, but it is unknown if NAFLD itself influences the effects of sugars on plasma lipoproteins. To study this further, men with NAFLD ( n = 11) and low liver fat 'controls' ( n = 14) were fed two iso-energetic diets, high or low in sugars (26% or 6% total energy) for 12 weeks, in a randomised, cross-over design. Fasting plasma lipid and lipoprotein kinetics were measured after each diet by stable isotope trace-labelling.There were significant differences in the production and catabolic rates of VLDL subclasses between men with NAFLD and controls, in response to the high and low sugar diets. Men with NAFLD had higher plasma concentrations of VLDL 1 -triacylglycerol (TAG) after the high ( P sugar ( P diets, a lower VLDL 1 -TAG fractional catabolic rate after the high sugar diet ( P sugar diet ( P sugar diet, was to channel hepatic TAG into a higher production of VLDL 1 -TAG ( P sugars. © 2017 The Author(s).

  14. Isocaloric high-fat feeding directs hepatic metabolism to handling of nutrient imbalance promoting liver fat deposition

    KAUST Repository

    Diaz Rua, Ruben; Van Schothorst, E. M.; Keijer, J.; Palou, A.; Oliver, P.

    2016-01-01

    Background/Objectives: Consumption of fat-rich foods is associated with obesity and related alterations. However, there is a group of individuals, the metabolically obese normal-weight (MONW) subjects, who present normal body weight but have metabolic features characteristic of the obese status, including fat deposition in critical tissues such as liver, recognized as a major cause for the promotion of metabolic diseases. Our aim was to better understand metabolic alterations present in liver of MONW rats applying whole genome transcriptome analysis. Methods: Wistar rats were chronically fed a high-fat diet isocaloric relative to Control animals to avoid the hyperphagia and overweight and to mimic MONW features. Liver transcriptome analysis of both groups was performed. Results: Sustained intake of an isocaloric high-fat diet had a deep impact on the liver transcriptome, mainly affecting lipid metabolism. Although serum cholesterol levels were not affected, circulating triacylglycerols were lower, and metabolic adaptations at gene expression level indicated adaptation toward handling the increased fat content of the diet, an increased triacylglycerol and cholesterol deposition in liver of MONW rats was observed. Moreover, gene expression pointed to increased risk of liver injury. One of the top upregulated genes in this tissue was Krt23, a marker of hepatic disease in humans that was also increased at the protein level.Conclusion:Long-term intake of a high-fat diet, even in the absence of overweight/obesity or increase in classical blood risk biomarkers, promotes a molecular environment leading to hepatic lipid accumulation and increasing the risk of suffering from hepatic diseases.

  15. Isocaloric high-fat feeding directs hepatic metabolism to handling of nutrient imbalance promoting liver fat deposition

    KAUST Repository

    Diaz Rua, Ruben

    2016-03-22

    Background/Objectives: Consumption of fat-rich foods is associated with obesity and related alterations. However, there is a group of individuals, the metabolically obese normal-weight (MONW) subjects, who present normal body weight but have metabolic features characteristic of the obese status, including fat deposition in critical tissues such as liver, recognized as a major cause for the promotion of metabolic diseases. Our aim was to better understand metabolic alterations present in liver of MONW rats applying whole genome transcriptome analysis. Methods: Wistar rats were chronically fed a high-fat diet isocaloric relative to Control animals to avoid the hyperphagia and overweight and to mimic MONW features. Liver transcriptome analysis of both groups was performed. Results: Sustained intake of an isocaloric high-fat diet had a deep impact on the liver transcriptome, mainly affecting lipid metabolism. Although serum cholesterol levels were not affected, circulating triacylglycerols were lower, and metabolic adaptations at gene expression level indicated adaptation toward handling the increased fat content of the diet, an increased triacylglycerol and cholesterol deposition in liver of MONW rats was observed. Moreover, gene expression pointed to increased risk of liver injury. One of the top upregulated genes in this tissue was Krt23, a marker of hepatic disease in humans that was also increased at the protein level.Conclusion:Long-term intake of a high-fat diet, even in the absence of overweight/obesity or increase in classical blood risk biomarkers, promotes a molecular environment leading to hepatic lipid accumulation and increasing the risk of suffering from hepatic diseases.

  16. Hepatitis Vaccines

    OpenAIRE

    Ogholikhan, Sina; Schwarz, Kathleen B.

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B ...

  17. {sup 18}F-FDG uptake at the surgical margin after hepatic resection: Patterns of uptake and differential diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Peungjesada, Silanath [University New Mexico, Department of Radiology, Albuquerque, NM (United States); Aloia, Thomas A. [University of Texas MD Anderson Cancer Center, Department of Surgical Oncology, Unit 444, Houston, TX (United States); Fox, Patricia [University of Texas MD Anderson Cancer Center, Department of Biostatistics, Unit 1411, Houston, TX (United States); Chasen, Beth [University of Texas MD Anderson Cancer Center, Department of Nuclear Medicine, Unit 1483, Houston, TX (United States); Shin, Sooyoung; Loyer, Evelyne M. [University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Unit 1473, Houston, TX (United States); Baiomy, Ali [Cairo University, National Cancer Center, Cairo (Egypt)

    2015-08-15

    To evaluate the patterns of {sup 18}F-FDG uptake at the surgical margin after hepatectomy to identify features that may differentiate benign and malignant uptake. Patients who had undergone a PET/CT after hepatectomy were identified. Delay between resection and PET/CT, presence of uptake at the surgical margin, pattern of uptake, and maximal standardized value were recorded. The PET/CT findings were correlated with contrast-enhanced CT or MRI. There were 26 patients with increased 18F-FDG uptake; uptake was diffuse in seven and focal in 19. Diffuse uptake was due to inflammation in all cases. Focal uptake was due to recurrence in 12 and inflammation in seven cases. Defining a focal pattern only as a positive for malignancy yielded 100 % sensitivity, 87 % specificity, 37 % false positive rate. As expected, SUV{sub max} was significantly higher for recurrence than inflammation, but did overlap. Contrast-enhanced CT allowed differentiation between malignant and benign uptake in all cases. F-FDG uptake after hepatectomy does not equate to recurrence and yields a high false positive rate. Diffuse uptake did not require additional evaluation in our sample. Focal uptake, however, may be due to recurrence; differentiating benign and malignant nodular uptake relies on optimal contrast-enhanced CT or MRI. (orig.)

  18. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Donate Today Enroll in 123 What is Hepatic Encephalopathy? Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy or PSE, is a condition that causes temporary ...

  19. Torsed pedunculated hepatic hamartoma

    International Nuclear Information System (INIS)

    Vazquez-Lima, Ignacio; Vazquez, Jose L.; Gallego, Marta; Fernandez, Rebeca; Fernandez, Pilar

    2009-01-01

    We report a 9-year-old boy with a 6-h history of acute abdominal pain due to torsion of a pedunculated hepatic mesenchymal hamartoma. The lesion was seen, on US and CT, to connect to the liver through a pedicle. Mesenchymal hepatic hamartomas are unusual tumours that may be pedunculated, and this is a unique case complicated by torsion. The radiological and pathological findings, differential diagnosis, and clinical course are discussed. (orig.)

  20. An engineered cell-imprinted substrate directs osteogenic differentiation in stem cells

    DEFF Research Database (Denmark)

    Kamguyan, Khorshid; Katbab, Ali Asghar; Mahmoudi, Morteza

    2018-01-01

    A cell-imprinted poly(dimethylsiloxane)/hydroxyapatite nanocomposite substrate was fabricated to engage topographical, mechanical, and chemical signals to stimulate and boost stem cell osteogenic differentiation. The physicochemical properties of the fabricated substrates, with nanoscale resolution...

  1. Magnetic Resonance Elastography: Measurement of Hepatic Stiffness Using Different Direct Inverse Problem Reconstruction Methods in Healthy Volunteers and Patients with Liver Disease.

    Science.gov (United States)

    Saito, Shigeyoshi; Tanaka, Keiko; Hashido, Takashi

    2016-02-01

    The purpose of this study was to compare the mean hepatic stiffness values obtained by the application of two different direct inverse problem reconstruction methods to magnetic resonance elastography (MRE). Thirteen healthy men (23.2±2.1 years) and 16 patients with liver diseases (78.9±4.3 years; 12 men and 4 women) were examined for this study using a 3.0 T-MRI. The healthy volunteers underwent three consecutive scans, two 70-Hz waveform and a 50-Hz waveform scans. On the other hand, the patients with liver disease underwent scanning using the 70-Hz waveform only. The MRE data for each subject was processed twice for calculation of the mean hepatic stiffness (Pa), once using the multiscale direct inversion (MSDI) and once using the multimodel direct inversion (MMDI). There were no significant differences in the mean stiffness values among the scans obtained with two 70-Hz and different waveforms. However, the mean stiffness values obtained with the MSDI technique (with mask: 2895.3±255.8 Pa, without mask: 2940.6±265.4 Pa) were larger than those obtained with the MMDI technique (with mask: 2614.0±242.1 Pa, without mask: 2699.2±273.5 Pa). The reproducibility of measurements obtained using the two techniques was high for both the healthy volunteers [intraclass correlation coefficients (ICCs): 0.840-0.953] and the patients (ICC: 0.830-0.995). These results suggest that knowledge of the characteristics of different direct inversion algorithms is important for longitudinal liver stiffness assessments such as the comparison of different scanners and evaluation of the response to fibrosis therapy.

  2. Introduction of the second-generation direct-acting antivirals (DAAs) in chronic hepatitis C: a register-based study in Sweden.

    Science.gov (United States)

    Frisk, P; Aggefors, K; Cars, T; Feltelius, N; Loov, S A; Wettermark, B; Weiland, O

    2018-07-01

    Introduction of the direct-acting antivirals (DAAs) for treatment of chronic hepatitis C (CHC) infection has been challenging in all health systems. In Sweden, a national protocol for managed introduction was developed. It was optional, but all county councils agreed to implement and follow it. The purpose of this study was to study (a) cure rates among all patients initiated on treatment in 2014-2015, (b) prescribers' adherence to the drug recommendations and treatment eligibility criteria in the protocol, and (c) introduction rate in the six Swedish healthcare regions. A cross-sectional study where national data from the Prescribed Drug Register and the quality register InfCare Hepatitis defined the study population, and clinical data from the Patient Register and InfCare Hepatitis were used to monitor outcomes. Descriptive statistics were used. A total of 3447 patients were initiated on treatment during 2014-2015. The overall cure rate, based on data from 85% of the cohort, was 96%, with variation between genotypes. Adherence to drug recommendations increased over time and varied between 43.2 and 94.2%. Adherence to the treatment eligibility criteria was initially 80% and increased to 87% when treatment restrictions were widened. The introduction rate differed initially between the regions and reached stable levels 15-18 months after the launch of the first DAA. The estimated overall cure rate was 96%, with some variations between genotypes. A high level of adherence to the introduction protocol as well as similar introduction rates in the health care regions indicate that the introduction protocol, alongside with other measures taken, contributed considerably to a rapid uptake and equal distribution of DAAs in Sweden.

  3. Research priorities to achieve universal access to hepatitis C prevention, management and direct-acting antiviral treatment among people who inject drugs.

    Science.gov (United States)

    Grebely, Jason; Bruneau, Julie; Lazarus, Jeffrey V; Dalgard, Olav; Bruggmann, Philip; Treloar, Carla; Hickman, Matthew; Hellard, Margaret; Roberts, Teri; Crooks, Levinia; Midgard, Håvard; Larney, Sarah; Degenhardt, Louisa; Alho, Hannu; Byrne, Jude; Dillon, John F; Feld, Jordan J; Foster, Graham; Goldberg, David; Lloyd, Andrew R; Reimer, Jens; Robaeys, Geert; Torrens, Marta; Wright, Nat; Maremmani, Icro; Norton, Brianna L; Litwin, Alain H; Dore, Gregory J

    2017-09-01

    Globally, it is estimated that 71.1 million people have chronic hepatitis C virus (HCV) infection, including an estimated 7.5 million people who have recently injected drugs (PWID). There is an additional large, but unquantified, burden among those PWID who have ceased injecting. The incidence of HCV infection among current PWID also remains high in many settings. Morbidity and mortality due to liver disease among PWID with HCV infection continues to increase, despite the advent of well-tolerated, simple interferon-free direct-acting antiviral (DAA) HCV regimens with cure rates >95%. As a result of this important clinical breakthrough, there is potential to reverse the rising burden of advanced liver disease with increased treatment and strive for HCV elimination among PWID. Unfortunately, there are many gaps in knowledge that represent barriers to effective prevention and management of HCV among PWID. The Kirby Institute, UNSW Sydney and the International Network on Hepatitis in Substance Users (INHSU) established an expert round table panel to assess current research gaps and establish future research priorities for the prevention and management of HCV among PWID. This round table consisted of a one-day workshop held on 6 September, 2016, in Oslo, Norway, prior to the International Symposium on Hepatitis in Substance Users (INHSU 2016). International experts in drug and alcohol, infectious diseases, and hepatology were brought together to discuss the available scientific evidence, gaps in research, and develop research priorities. Topics for discussion included the epidemiology of injecting drug use, HCV, and HIV among PWID, HCV prevention, HCV testing, linkage to HCV care and treatment, DAA treatment for HCV infection, and reinfection following successful treatment. This paper highlights the outcomes of the roundtable discussion focused on future research priorities for enhancing HCV prevention, testing, linkage to care and DAA treatment for PWID as we strive

  4. Autoimmune hepatitis.

    Science.gov (United States)

    Vergani, D; Mieli-Vergani, G

    2004-06-01

    Autoimmune hepatitis (AIH) is characterised histologically by interface hepatitis, and serologically by the presence of non-organ and liver specific autoantibodies and increased levels of immunoglobulin G. Its onset is often ill-defined, frequently mimicing acute hepatitis. AIH usually responds to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Two types of AIH are recognized according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1 AIH) or liver kidney microsomal type 1 antibody (LKM1, type 2 AIH). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age and commonly have immunoglobulin A deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in the 2 groups. Susceptibility to AIH type 1 is conferred by possession of HLA DR3 and DR4, while to AIH type 2 by possession of HLA DR7. Liver damage is likely to derive from an immune reaction to liver cell antigens, possibly triggered by a mechanism of molecular mimicry, where immune responses to external pathogens, e.g. viruses, become directed towards structurally similar self-components. In AIH this process would be perpetuated by impairment in immune regulation.

  5. Limited value of fluorine-18-fluorodeoxyglucose PET for the differential diagnosis of focal liver lesions in patients with chronic hepatitis C virus infection

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, O. [Frankfurt Univ. (Germany). Dept. of Nuclear Medicine]|[Frankfurt Univ. (Germany). 2. Dept. of Internal Medicine; Trojan, J.; Zeuzem, S. [Frankfurt Univ. (Germany). 2. Dept. of Internal Medicine; Baum, R.P. [Frankfurt Univ. (Germany). Dept. of Nuclear Medicine

    1998-12-31

    Aim: The differentiation of HCC from liver metastasis or benign disorders by imaging studies based upon morphological aspects may be difficult. Method: In order to evaluate the role of tumour metabolism, we performed FDG-PET (whole-body PET and transmission-corrected regional scans of the liver as well as the SUV determined 60 min after injection of FDG) in ten consecutive patients with HCV-associated focal liver lesions. Definite diagnosis was established after ultrasound-guided liver biopsy followed by histopathological examination. These results were compared with ultrasound, computed tomography, serum anti-p53, and p53 protein expression. Results: The histologic examination revealed a HCC in five patients, regenerative nodules in three patients, and liver metastasis (primary malignancy: One adenocarcinoma and one neuroendocrine tumour) in the remaining two patients. Three of ten lesions were detectable by FDG-PET: two HCCs and one metastatic adenocarcinoma. Seven lesions were not distinguishable by FDG-PET (three HCCs, three regeneration nodules and one metastatic neuroendocrine tumour). In each patient hepatic lesions were visible either by ultrasound or CT. Both tumours (metatatic adenocarcinoma, moderately well-differentiated HCC) with the strongest expression of p53 also presented with highly increased FDG uptake. Conclusions: FDG-PET is not superior to ultrasound or CT and therefore does not allow the non-invasive differentiation of HCV-associated focal liver lesions. Tissue-diagnosis by means of liver-biopsy followed by histopathological examination remains the gold-standard for the differentiation of HCV-related liver lesions. The finding of the relationship of p53 protein overexpression with the SUV needs further confirmation. (orig.) [Deutsch] Ziel: Eine Differenzierung des hepatozellulaeren Karzinoms (HCC) gegenueber Lebermetastasen oder benignen Erkrankungen ist durch Einsatz morphologischer bildgebender Verfahren nicht immer moeglich. Untersuchungen

  6. Direct-acting antiviral-based triple therapy on alpha-fetoprotein level in chronic hepatitis C patients.

    Science.gov (United States)

    Takayama, Koji; Furusyo, Norihiro; Ogawa, Eiichi; Ikezaki, Hiroaki; Shimizu, Motohiro; Murata, Masayuki; Hayashi, Jun

    2015-04-21

    To investigate the impact of telaprevir-based triple therapy on the serum alpha-fetoprotein (AFP) level of chronic hepatitis C patients. A total of 210 patients with chronic hepatitis C genotype 1 of high viral load (baseline serum hepatitis C virus RNA > 5.0 log10 IU/mL) were divided into two groups by type of treatment: triple therapy with telaprevir, pegylated-interferon-α (PEG-IFNα), and ribavirin (RBV) for 24 wk (n = 88), or dual therapy with PEG-IFNα and RBV for 48 wk (n = 122). The relationship between virological response and the change in the serum AFP level from baseline to 24 wk after the end of treatment was examined. No significant difference in mean baseline AFP level was found between the triple and dual therapy groups (8.8 ng/mL vs 7.8 ng/mL). Triple therapy produced significant declines in the AFP level in sustained virological response (SVR) and non-SVR patients (7.8 ng/mL at baseline to 3.5 ng/mL at 24 wk after the end of treatment, P < 0.001 and 14.3 ng/mL to 9.5 ng/mL, P = 0.004, respectively). In contrast, dual therapy resulted in a significant decline in AFP level only in SVR patients (4.7 ng/mL to 2.8 ng/mL, P < 0.001), but not in non-SVR patients (10.2 ng/mL to 10.1 ng/mL). Among patients with a high-baseline AFP level (≥ 10 ng/mL), the decline in the AFP level was significantly higher in the triple therapy than in the dual therapy group (15.9 ng/mL vs 1.6 ng/mL, P = 0.037). Regardless of virological response, telaprevir-based triple therapy reduced the serum AFP level.

  7. Differential functions of C- and N-terminal hepatitis B x protein in liver cells treated with doxorubicin in normoxic or hypoxic condition.

    Directory of Open Access Journals (Sweden)

    Davor Kin-Fan Chau

    Full Text Available Hepatitis viral B x protein (HBx, a hepatocarcinogen, is frequently mutated. Hypoxia influences the growth of HCC and also the sensitivity of tumor cells to treatments. We aimed to test the role of HBx and acute hypoxia in the efficacy of chemotherapy. In this study, we established 4 Chang liver cell lines with the full-length HBx (HBx, the first 50 amino acids of N-terminal HBx (HBx/50, the last 104 amino acids of C-terminal HBx (HBx/51 and empty vector (CL, respectively. MTT and TNUEL assays were used to assess cell viability and apoptosis respectively. Western blot was used to determine the expression of relevant proteins. Results showed that among 4 cell lines, doxorubicin was most effective in decreasing the viability and enhancing apoptosis in HBx/51 cells, while HBx/50 cells were most resistant to the treatment. Cells in hypoxia were more susceptible to doxorubicin than cells in normoxia. Hypoxia facilitated the Bid cleavage especially in HBx/51 cells via phosphorylating p38 MAPK. p38 MAPK inhibitor significantly reduced the tBid level and increased cell viability. In conclusion, N-terminal HBx and C-terminal HBx function differentially in their ability to regulate cell growth, with the former being promotive but the latter being inhibitory. The acute hypoxia may overcome the HBx-induced resistance and facilitate the chemotherapy.

  8. Chronic hepatitis C virus infection triggers spontaneous differential expression of biosignatures associated with T cell exhaustion and apoptosis signaling in peripheral blood mononucleocytes.

    Science.gov (United States)

    Barathan, Muttiah; Gopal, Kaliappan; Mohamed, Rosmawati; Ellegård, Rada; Saeidi, Alireza; Vadivelu, Jamuna; Ansari, Abdul W; Rothan, Hussin A; Ravishankar Ram, M; Zandi, Keivan; Chang, Li Y; Vignesh, Ramachandran; Che, Karlhans F; Kamarulzaman, Adeeba; Velu, Vijayakumar; Larsson, Marie; Kamarul, Tunku; Shankar, Esaki M

    2015-04-01

    Persistent hepatitis C virus (HCV) infection appears to trigger the onset of immune exhaustion to potentially assist viral persistence in the host, eventually leading to hepatocellular carcinoma. The role of HCV on the spontaneous expression of markers suggestive of immune exhaustion and spontaneous apoptosis in immune cells of chronic HCV (CHC) disease largely remain elusive. We investigated the peripheral blood mononuclear cells of CHC patients to determine the spontaneous recruitment of cellular reactive oxygen species (cROS), immunoregulatory and exhaustion markers relative to healthy controls. Using a commercial QuantiGenePlex(®) 2.0 assay, we determined the spontaneous expression profile of 80 different pro- and anti-apoptotic genes in persistent HCV disease. Onset of spontaneous apoptosis significantly correlated with the up-regulation of cROS, indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2/prostaglandin H synthase (COX-2/PGHS), Foxp3, Dtx1, Blimp1, Lag3 and Cd160. Besides, spontaneous differential surface protein expression suggestive of T cell inhibition viz., TRAIL, TIM-3, PD-1 and BTLA on CD4+ and CD8+ T cells, and CTLA-4 on CD4+ T cells was also evident. Increased up-regulation of Tnf, Tp73, Casp14, Tnfrsf11b, Bik and Birc8 was observed, whereas FasLG, Fas, Ripk2, Casp3, Dapk1, Tnfrsf21, and Cflar were moderately up-regulated in HCV-infected subjects. Our observation suggests the spontaneous onset of apoptosis signaling and T cell exhaustion in chronic HCV disease.

  9. The hepatitis C virus Core protein is a potent nucleic acid chaperone that directs dimerization of the viral (+) strand RNA in vitro.

    Science.gov (United States)

    Cristofari, Gaël; Ivanyi-Nagy, Roland; Gabus, Caroline; Boulant, Steeve; Lavergne, Jean-Pierre; Penin, François; Darlix, Jean-Luc

    2004-01-01

    The hepatitis C virus (HCV) is an important human pathogen causing chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV is an enveloped virus with a positive-sense, single-stranded RNA genome encoding a single polyprotein that is processed to generate viral proteins. Several hundred molecules of the structural Core protein are thought to coat the genome in the viral particle, as do nucleocapsid (NC) protein molecules in Retroviruses, another class of enveloped viruses containing a positive-sense RNA genome. Retroviral NC proteins also possess nucleic acid chaperone properties that play critical roles in the structural remodelling of the genome during retrovirus replication. This analogy between HCV Core and retroviral NC proteins prompted us to investigate the putative nucleic acid chaperoning properties of the HCV Core protein. Here we report that Core protein chaperones the annealing of complementary DNA and RNA sequences and the formation of the most stable duplex by strand exchange. These results show that the HCV Core is a nucleic acid chaperone similar to retroviral NC proteins. We also find that the Core protein directs dimerization of HCV (+) RNA 3' untranslated region which is promoted by a conserved palindromic sequence possibly involved at several stages of virus replication.

  10. A new index for differential diagnosis between mild hepatic lesions associated with chronic alcoholism (steatosis, steatofibrosis) and severe alcoholic liver disease (cirrhosis) by a combination of an aminopyrine breath test and a colloid hepatosplenic scintigraphy

    International Nuclear Information System (INIS)

    Urbain, D.; Jeghers, O.; Lenaers, A.; Wanet, P.; Abramovici, J.; Preux, C.

    1984-01-01

    The severity of liver disease is related not only to the degree of hepatocellular lesions but also to the hemodynamic changes created by extensive fibrosis. Theoretically, the combination of two tests providing information on these two aspects should allow a better identification of patients with severe alcoholic liver disease. In the present work our new functional index clearly improves the ability in differentiating mild alcoholic hepatic lesions from alcoholic cirrhosis. (orig.)

  11. Cost-effectiveness analysis of two treatment strategies for chronic hepatitis C before and after access to direct-acting antivirals in Spain.

    Science.gov (United States)

    Turnes, Juan; Domínguez-Hernández, Raquel; Casado, Miguel Ángel

    To evaluate the cost-effectiveness of a strategy based on direct-acting antivirals (DAAs) following the marketing of simeprevir and sofosbuvir (post-DAA) versus a pre-direct-acting antiviral strategy (pre-DAA) in patients with chronic hepatitis C, from the perspective of the Spanish National Health System. A decision tree combined with a Markov model was used to estimate the direct health costs (€, 2016) and health outcomes (quality-adjusted life years, QALYs) throughout the patient's life, with an annual discount rate of 3%. The sustained virological response, percentage of patients treated or not treated in each strategy, clinical characteristics of the patients, annual likelihood of transition, costs of treating and managing the disease, and utilities were obtained from the literature. The cost-effectiveness analysis was expressed as an incremental cost-effectiveness ratio (incremental cost per QALY gained). A deterministic sensitivity analysis and a probabilistic sensitivity analysis were performed. The post-DAA strategy showed higher health costs per patient (€30,944 vs. €23,707) than the pre-DAA strategy. However, it was associated with an increase of QALYs gained (15.79 vs. 12.83), showing an incremental cost-effectiveness ratio of €2,439 per QALY. The deterministic sensitivity analysis and the probabilistic sensitivity analysis showed the robustness of the results, with the post-DAA strategy being cost-effective in 99% of cases compared to the pre-DAA strategy. Compared to the pre-DAA strategy, the post-DAA strategy is efficient for the treatment of chronic hepatitis C in Spain, resulting in a much lower cost per QALY than the efficiency threshold used in Spain (€30,000 per QALY). Copyright © 2017 Elsevier España, S.L.U., AEEH y AEG. All rights reserved.

  12. Cell population structure prior to bifurcation predicts efficiency of directed differentiation in human induced pluripotent cells.

    Science.gov (United States)

    Bargaje, Rhishikesh; Trachana, Kalliopi; Shelton, Martin N; McGinnis, Christopher S; Zhou, Joseph X; Chadick, Cora; Cook, Savannah; Cavanaugh, Christopher; Huang, Sui; Hood, Leroy

    2017-02-28

    Steering the differentiation of induced pluripotent stem cells (iPSCs) toward specific cell types is crucial for patient-specific disease modeling and drug testing. This effort requires the capacity to predict and control when and how multipotent progenitor cells commit to the desired cell fate. Cell fate commitment represents a critical state transition or "tipping point" at which complex systems undergo a sudden qualitative shift. To characterize such transitions during iPSC to cardiomyocyte differentiation, we analyzed the gene expression patterns of 96 developmental genes at single-cell resolution. We identified a bifurcation event early in the trajectory when a primitive streak-like cell population segregated into the mesodermal and endodermal lineages. Before this branching point, we could detect the signature of an imminent critical transition: increase in cell heterogeneity and coordination of gene expression. Correlation analysis of gene expression profiles at the tipping point indicates transcription factors that drive the state transition toward each alternative cell fate and their relationships with specific phenotypic readouts. The latter helps us to facilitate small molecule screening for differentiation efficiency. To this end, we set up an analysis of cell population structure at the tipping point after systematic variation of the protocol to bias the differentiation toward mesodermal or endodermal cell lineage. We were able to predict the proportion of cardiomyocytes many days before cells manifest the differentiated phenotype. The analysis of cell populations undergoing a critical state transition thus affords a tool to forecast cell fate outcomes and can be used to optimize differentiation protocols to obtain desired cell populations.

  13. Nitazoxanide for chronic hepatitis C

    DEFF Research Database (Denmark)

    Nikolova, Kristiana; Gluud, Christian; Grevstad, Berit

    2014-01-01

    BACKGROUND: Hepatitis C infection is a disease of the liver caused by the hepatitis C virus. The estimated number of chronically infected people with hepatitis C virus worldwide is about 150 million people. Every year, another three to four million people acquire the infection. Chronic hepatitis C......) and ribavirin was the approved standard treatment for chronic hepatitis C. In 2011, first-generation direct-acting antivirals (DAAs) have been licensed, for use in combination with peginterferon and ribavirin for treating hepatitis C virus genotype 1 infection. Nitazoxanide is another antiviral drug with broad...... antiviral activity and may have potential as an effective alternative, or an addition to standard treatment for the treatment of the hepatitis C virus. OBJECTIVES: To assess the benefits and harms of nitazoxanide in people with chronic hepatitis C virus infection. SEARCH METHODS: We searched The Cochrane...

  14. A direct indication of plasma potential diagnostic with fast time response and high accuracy based on a differential emissive probe

    International Nuclear Information System (INIS)

    Yao, W.E.; Hershkowitz; Intrator, T.

    1985-01-01

    The floating potential of the emissive probe has been used to directly measure the plasma potential. The authors have recently presented another method for directly indicating the plasma potential with a differential emissive probe. In this paper they describe the effects of probe size, plasma density and plasma potential fluctuation on plasma potential measurements and give methods for reducing errors. A control system with fast time response (α 20 μs) and high accuracy (the order of the probe temperature T/sub w//e) for maintaining a differential emissive probe at plasma potential has been developed. It can be operated in pulsed discharge plasma to measure plasma potential dynamic characteristics. A solid state optical coupler is employed to improve circuit performance. This system was tested experimentally by measuring the plasma potential in an argon plasma device an on the Phaedrus tandem mirror

  15. A direct indication of plasma potential diagnostic with fast time response and high accuracy based on a differential emissive probe

    International Nuclear Information System (INIS)

    Yao, W.E.; Hershkowitz, N.; Intrator, T.

    1985-01-01

    The floating potential of the emissive probe has been used to directly measure the plasma potential. The authors have recently presented another method for directly indicating the plasma potential with a differential emissive probe. In this paper they describe the effects of probe size, plasma density and plasma potential fluctuation on plasma potential measurements and give methods for reducing errors. A control system with fast time response (≅ 20 μs) and high accuracy (the order of the probe temperature T/sub w//e) for maintaining a differential emissive probe at plasma potential has been developed. It can be operated in pulsed discharge plasma to measure plasma potential dynamic characteristics. A solid state optical coupler is employed to improve circuit performance. This system was tested experimentally by measuring the plasma potential in an argon plasma device and on the Phaedrus tandem mirror

  16. Hepatitis C: Managing Pain

    Science.gov (United States)

    ... Pain: Entire Lesson Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For Veterans and the Public Veterans and the Public Home Hepatitis A Hepatitis B Hepatitis C Hepatitis C Home Getting ...

  17. Mycobacterium tuberculosis directs T helper 2 cell differentiation by inducing interleukin-1β production in dendritic cells.

    Science.gov (United States)

    Dwivedi, Ved Prakash; Bhattacharya, Debapriya; Chatterjee, Samit; Prasad, Durbaka Vijay Raghva; Chattopadhyay, Debprasad; Van Kaer, Luc; Bishai, William R; Das, Gobardhan

    2012-09-28

    Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), resides and replicates within phagocytes and persists in susceptible hosts by modulating protective innate immune responses. Furthermore, M. tuberculosis promotes T helper 2 (Th2) immune responses by altering the balance of T cell polarizing cytokines in infected cells. However, cytokines that regulate Th2 cell differentiation during TB infection remain unknown. Here we show that IL-1β, produced by phagocytes infected by virulent M. tuberculosis strain H37Rv, directs Th2 cell differentiation. In sharp contrast, the vaccine strain bacille Calmette-Guérin as well as RD-1 and ESAT-6 mutants of H37Rv failed to induce IL-1β and promote Th2 cell differentiation. Furthermore, ESAT-6 induced IL-1β production in dendritic cells (DCs), and CD4(+) T cells co-cultured with infected DCs differentiated into Th2 cells. Taken together, our findings indicate that IL-1β induced by RD-1/ESAT-6 plays an important role in the differentiation of Th2 cells, which in turn facilitates progression of TB by inhibiting host protective Th1 responses.

  18. Small-Molecule-Directed Hepatocyte-Like Cell Differentiation of Human Pluripotent Stem Cells.

    Science.gov (United States)

    Mathapati, Santosh; Siller, Richard; Impellizzeri, Agata A R; Lycke, Max; Vegheim, Karianne; Almaas, Runar; Sullivan, Gareth J

    2016-08-17

    Hepatocyte-like cells (HLCs) generated in vitro from human pluripotent stem cells (hPSCs) provide an invaluable resource for basic research, regenerative medicine, drug screening, toxicology, and modeling of liver disease and development. This unit describes a small-molecule-driven protocol for in vitro differentiation of hPSCs into HLCs without the use of growth factors. hPSCs are coaxed through a developmentally relevant route via the primitive streak to definitive endoderm (DE) using the small molecule CHIR99021 (a Wnt agonist), replacing the conventional growth factors Wnt3A and activin A. The small-molecule-derived DE is then differentiated to hepatoblast-like cells in the presence of dimethyl sulfoxide. The resulting hepatoblasts are then differentiated to HLCs with N-hexanoic-Tyr, Ile-6 aminohexanoic amide (Dihexa, a hepatocyte growth factor agonist) and dexamethasone. The protocol provides an efficient and reproducible procedure for differentiation of hPSCs into HLCs utilizing small molecules. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

  19. Predominance of hepatitis C virus Q80K among NS3 baseline-resistance-associated amino acid variants in direct-antiviral-agent-naïve patients with chronic hepatitis: single-centre experience.

    Science.gov (United States)

    Ruggiero, Tina; Proietti, Alex; Boglione, Lucio; Milia, Maria Grazia; Allice, Tiziano; Burdino, Elisa; Orofino, Giancarlo; Bonora, Stefano; Di Perri, Giovanni; Ghisetti, Valeria

    2015-11-01

    In the era of direct-acting antiviral agents (DAAs), hepatitis C virus (HCV) genotyping tests at baseline are controversial. The HCV NS3-Q80K polymorphism is associated with resistance to the recently approved NS3 inhibitor simeprevir (SMV) when combined with PEG-interferon and ribavirin (PEG-IFN/RBV) and alternative therapy should be considered for patients with baseline Q80K. The aim of this study was to provide an estimate of Q80K prevalence at baseline in a study group of 205 DAA-naïve patients (21% of them with HIV coinfection) using NS3 full-population direct sequencing to detect resistance-associated amino acid variants (RAVs). NS3 RAVs were identified in 56 patients (27.3%). Q80K was the most frequently reported one (41%), in both HIV/HCV-coinfected and HCV-monoinfected patients, but it was only detectable in cases of HCV-subtype 1a infection. Therefore, in clinical practice, an NS3-Q80K genotyping test prior to simeprevir plus PEG-IFN/RBV treatment is highly recommended.

  20. MicroRNA-24 promotes 3T3-L1 adipocyte differentiation by directly targeting the MAPK7 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Min, E-mail: min_jin@zju.edu.cn [Division of Reproductive Medicine & Infertility, The Second Affiliated Hospital, School of Medicine, Zhejiang University, 88#, Jiefang Rd., Hangzhou, Zhejiang, 310009 (China); Wu, Yutao; Wang, Jing [School of Medicine, Zhejiang University, 288# Yuhangtang Rd, Hangzhou, Zhejiang, 310003 (China); Chen, Jian; Huang, Yiting; Rao, Jinpeng; Feng, Chun [Division of Reproductive Medicine & Infertility, The Second Affiliated Hospital, School of Medicine, Zhejiang University, 88#, Jiefang Rd., Hangzhou, Zhejiang, 310009 (China)

    2016-05-20

    Over the past years, MicroRNAs (miRNAs) act as a vital role in harmony with gene regulation and maintaining cellular homeostasis. It is well testified that miRNAshave been involved in numerous physiological and pathological processes, including embryogenesis, cell fate decision, and cellular differentiation. Adipogenesis is an organized process of cellular differentiation by which pre-adipocytes differentiate towards mature adipocytes, and it is tightly modulated by a series of transcription factors such as peroxisome proliferator-activated receptor γ (PPAR-γ) and sterol regulatory-element binding proteins 1 (SREBP1). However, the molecular mechanisms underlying the connection between miRNAs and adipogenesis-related transcription factors remain obscure. In this study, we unveiled that miR- 24 was remarkably upregulated during 3T3-L1 adipogenesis. Overexpression of miR-24 significantly promoted 3T3-L1 adipogenesis, as evidenced by its ability to increase the expression of PPAR-γ and SREBP1, lipid droplet formation and triglyceride (TG) accumulation. Furthermore, we found that neither ectopic expression of miR-24nor miR-24 inhibitor affect cell proliferation and cell cycle progression. Finally, we demonstrated that miR-24 plays the modulational role by directly repressing MAPK7, a key number in the MAPK signaling pathway. These data indicate that miR-24 is a novel positive regulator of adipocyte differentiation by targeting MAPK7, which provides new insights into the molecular mechanism of miRNA-mediated cellular differentiation. -- Highlights: •We firstly found miR-24 was upregulated in 3T3-L1 pre-adipocytes differentiation. •miR-24 promoted 3T3-L1 pre-adipocytes differentiation while silencing the expression of miR-24 had an opposite function. •miR-24 regulated 3T3-L1 differentiation by directly targeting MAPK7 signaling pathway. •miR-24did not affect 3T3-L1 pre-adipocytes cellular proliferation.

  1. Hepatic MR imaging for in vivo differentiation of steatosis, iron deposition and combined storage disorder: Single-ratio in/opposed phase analysis vs. dual-ratio Dixon discrimination

    International Nuclear Information System (INIS)

    Bashir, Mustafa R.; Merkle, Elmar M.; Smith, Alastair D.; Boll, Daniel T.

    2012-01-01

    Objective: To assess whether in vivo dual-ratio Dixon discrimination can improve detection of diffuse liver disease, specifically steatosis, iron deposition and combined disease over traditional single-ratio in/opposed phase analysis. Methods: Seventy-one patients with biopsy-proven (17.7 ± 17.0 days) hepatic steatosis (n = 16), iron deposition (n = 11), combined deposition (n = 3) and neither disease (n = 41) underwent MR examinations. Dual-echo in/opposed-phase MR with Dixon water/fat reconstructions were acquired. Analysis consisted of: (a) single-ratio hepatic region-of-interest (ROI)-based assessment of in/opposed ratios; (b) dual-ratio hepatic ROI assessment of in/opposed and fat/water ratios; (c) computer-aided dual-ratio assessment evaluating all hepatic voxels. Disease-specific thresholds were determined; statistical analyses assessed disease-dependent voxel ratios, based on single-ratio (a) and dual-ratio (b and c) techniques. Results: Single-ratio discrimination succeeded in identifying iron deposition (I/O Ironthreshold Fatthreshold>1.15 ) from normal parenchyma, sensitivity 70.0%; it failed to detect combined disease. Dual-ratio discrimination succeeded in identifying abnormal hepatic parenchyma (F/W Normalthreshold > 0.05), sensitivity 96.7%; logarithmic functions for iron deposition (I/O Iron d iscriminator (0.01−F/W Iron )/0.48 ) and for steatosis (I/O Fatdiscriminator > e (F/W Fat −0.01)/0.48 ) differentiated combined from isolated diseases, sensitivity 100.0%; computer-aided dual-ratio analysis was comparably sensitive but less specific, 90.2% vs. 97.6%. Conclusion: MR two-point-Dixon imaging using dual-ratio post-processing based on in/opposed and fat/water ratios improved in vivo detection of hepatic steatosis, iron deposition, and combined storage disease beyond traditional in/opposed analysis.

  2. Living biointerfaces based on non-pathogenic bacteria to direct cell differentiation

    Science.gov (United States)

    Rodrigo-Navarro, Aleixandre; Rico, Patricia; Saadeddin, Anas; Garcia, Andres J.; Salmeron-Sanchez, Manuel

    2014-07-01

    Genetically modified Lactococcus lactis, non-pathogenic bacteria expressing the FNIII7-10 fibronectin fragment as a protein membrane have been used to create a living biointerface between synthetic materials and mammalian cells. This FNIII7-10 fragment comprises the RGD and PHSRN sequences of fibronectin to bind α5β1 integrins and triggers signalling for cell adhesion, spreading and differentiation. We used L. lactis strain to colonize material surfaces and produce stable biofilms presenting the FNIII7-10 fragment readily available to cells. Biofilm density is easily tunable and remains stable for several days. Murine C2C12 myoblasts seeded over mature biofilms undergo bipolar alignment and form differentiated myotubes, a process triggered by the FNIII7-10 fragment. This biointerface based on living bacteria can be further modified to express any desired biochemical signal, establishing a new paradigm in biomaterial surface functionalisation for biomedical applications.

  3. Detecting consistent patterns of directional adaptation using differential selection codon models.

    Science.gov (United States)

    Parto, Sahar; Lartillot, Nicolas

    2017-06-23

    Phylogenetic codon models are often used to characterize the selective regimes acting on protein-coding sequences. Recent methodological developments have led to models explicitly accounting for the interplay between mutation and selection, by modeling the amino acid fitness landscape along the sequence. However, thus far, most of these models have assumed that the fitness landscape is constant over time. Fluctuations of the fitness landscape may often be random or depend on complex and unknown factors. However, some organisms may be subject to systematic changes in selective pressure, resulting in reproducible molecular adaptations across independent lineages subject to similar conditions. Here, we introduce a codon-based differential selection model, which aims to detect and quantify the fine-grained consistent patterns of adaptation at the protein-coding level, as a function of external conditions experienced by the organism under investigation. The model parameterizes the global mutational pressure, as well as the site- and condition-specific amino acid selective preferences. This phylogenetic model is implemented in a Bayesian MCMC framework. After validation with simulations, we applied our method to a dataset of HIV sequences from patients with known HLA genetic background. Our differential selection model detects and characterizes differentially selected coding positions specifically associated with two different HLA alleles. Our differential selection model is able to identify consistent molecular adaptations as a function of repeated changes in the environment of the organism. These models can be applied to many other problems, ranging from viral adaptation to evolution of life-history strategies in plants or animals.

  4. Adult subependymal neural precursors, but not differentiated cells, undergo rapid cathodal migration in the presence of direct current electric fields.

    Directory of Open Access Journals (Sweden)

    Robart Babona-Pilipos

    Full Text Available BACKGROUND: The existence of neural stem and progenitor cells (together termed neural precursor cells in the adult mammalian brain has sparked great interest in utilizing these cells for regenerative medicine strategies. Endogenous neural precursors within the adult forebrain subependyma can be activated following injury, resulting in their proliferation and migration toward lesion sites where they differentiate into neural cells. The administration of growth factors and immunomodulatory agents following injury augments this activation and has been shown to result in behavioural functional recovery following stroke. METHODS AND FINDINGS: With the goal of enhancing neural precursor migration to facilitate the repair process we report that externally applied direct current electric fields induce rapid and directed cathodal migration of pure populations of undifferentiated adult subependyma-derived neural precursors. Using time-lapse imaging microscopy in vitro we performed an extensive single-cell kinematic analysis demonstrating that this galvanotactic phenomenon is a feature of undifferentiated precursors, and not differentiated phenotypes. Moreover, we have shown that the migratory response of the neural precursors is a direct effect of the electric field and not due to chemotactic gradients. We also identified that epidermal growth factor receptor (EGFR signaling plays a role in the galvanotactic response as blocking EGFR significantly attenuates the migratory behaviour. CONCLUSIONS: These findings suggest direct current electric fields may be implemented in endogenous repair paradigms to promote migration and tissue repair following neurotrauma.

  5. 25 Gbit/s differential phase-shift-keying signal generation using directly modulated quantum-dot semiconductor optical amplifiers

    International Nuclear Information System (INIS)

    Zeghuzi, A.; Schmeckebier, H.; Stubenrauch, M.; Bimberg, D.; Meuer, C.; Schubert, C.; Bunge, C.-A.

    2015-01-01

    Error-free generation of 25-Gbit/s differential phase-shift keying (DPSK) signals via direct modulation of InAs quantum-dot (QD) based semiconductor optical amplifiers (SOAs) is experimentally demonstrated with an input power level of −5 dBm. The QD SOAs emit in the 1.3-μm wavelength range and provide a small-signal fiber-to-fiber gain of 8 dB. Furthermore, error-free DPSK modulation is achieved for constant optical input power levels from 3 dBm down to only −11 dBm for a bit rate of 20 Gbit/s. Direct phase modulation of QD SOAs via current changes is thus demonstrated to be much faster than direct gain modulation

  6. Identification of p63+ keratinocyte progenitor cells in circulation and their matrix-directed differentiation to epithelial cells.

    Science.gov (United States)

    Nair, Renjith P; Krishnan, Lissy K

    2013-04-11

    dermal fibroblast monolayer or fibrin supported cell proliferation and showed typical hexagonal morphology of keratinocytes within 15 days. Circulating KPCs were identified with p63, which differentiated into keratinocytes with expression of the cytokeratins, involucrin and filaggrin. Components of the specifically designed matrix favored KPC attachment, directed differentiation, and may turn out to be a potential vehicle for cell transplantation.

  7. Annexin A10 optimally differentiates between intrahepatic cholangiocarcinoma and hepatic metastases of pancreatic ductal adenocarcinoma: a comparative study of immunohistochemical markers and panels.

    Science.gov (United States)

    Kälsch, Julia; Padden, Juliet; Bertram, Stefanie; Pott, Leona L; Reis, Henning; Westerwick, Daniela; Schaefer, Christoph M; Sowa, Jan-P; Möllmann, Dorothe; Fingas, Christian; Dechȇne, Alexander; Sitek, Barbara; Eisenacher, Martin; Canbay, Ali; Ahrens, Maike; Baba, Hideo A

    2017-05-01

    Discriminating intrahepatic cholangiocarcinoma (ICC) from hepatic metastases of pancreatic ductal adenocarcinoma (mPDAC) can be challenging. While pathologists might depend on clinical information regarding a primary tumor, their diagnosis will lead the patient either to potentially curative surgery (for ICC) or to palliation (for mPDAC). Beyond the validation of recently published potential biomarkers for PDAC (primary or metastatic) in a large cohort, we assessed diagnostic performance of the most promising candidates in the challenging task of discriminating metastatic PDAC (mPDAC) from ICC. In a training set of 87 ICC and 88 pPDAC, our previously identified biomarkers Annexin A1 (ANXA1), ANXA10, and ANXA13 were tested and compared with 11 published biomarkers or panels (MUCIN 1, Agrin, S100P, MUC5 AC, Laminin, VHL, CK 17, N-Cadherin, ELAC2, PODXL and HSPG2). Biomarkers with best results were further tested in an independent series of biopsies of 27 ICC and 36 mPDAC. Highest AUC values (between 0.72 and 0.84) for the discrimination between ICC and pPDAC were found in the training set for Annexin A1, Annexin A10, MUC5 AC, CK17, and N-Cadherin. These markers were further tested on an independent series of liver biopsies containing ICC or mPDAC. Diagnostic characteristics were evaluated for individual markers as well as for 3× panels. ANXA 10 showed the highest diagnostic potential of all single markers, correctly classifying 75% of mPDAC and 85% of ICC. Our results suggest that ANXA10 may be useful to differentiate between ICC and mPDAC, when only a tissue specimen is available.

  8. Circulating regulatory Tfh cells are enriched in patients with chronic hepatitis B infection and induce the differentiation of regulatory B cells.

    Science.gov (United States)

    Wang, Rongxin; Xie, Ruiling; Song, Zongchang

    2018-04-15

    Chronic hepatitis B virus (HBV) infection is a complex disease with dysregulations in the immune system. Follicular helper T (Tfh) cells are professional B helper cells that are crucial to the development of antibody responses and are involved in a variety of diseases. In this study, we examined the circulating Tfh cells in patients with chronic HBV infection. We observed that CD3 + CD4 + CXCR5 + circulating Tfh cells contained a CD25 + Foxp3 + Treg-like subset that was significantly enriched in patients with chronic HBV infections. The CD25 + Tfh subset presented distinctive cytokine secretion profile, such as lower interferon (IFN)-γ and interleukin (IL)-17, and higher transforming growth factor (TGF)-β secretion, compared to the CD25 - Tfh subset. When incubated with autologous naive CD10 - CD27 - CD19 + B cells, the CD25 + Tfh subset was less capable of mediating CD20 -/lo CD38 + plasmablast differentiation than the CD25 - Tfh subset. In terms of Ig production, CD25 + Tfh cells were more potent at inducing IgM but less potent at inducing IgG and IgA than CD25 - Tfh cells. Interestingly, B cells following incubation with CD25 + Tfh cells presented elevated regulatory function, with higher production of IL-10 and enhanced capacity of suppressing autologous CD8 + T cell inflammation. In the chronic HBV-infected patients, the frequency of IL-10 + B cells and the HBV viral load were positively correlated with the frequency of CD25 + Foxp3 + CD4 + CXCR5 + Tfh cells. Together, this study presented that CD25 + Foxp3 + Treg-like Tfh cells were enriched in chronic HBV-infected patients and could promote regulatory B cell functions. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Ring-Like Enhancement of Hepatocellular Carcinoma in Gadoxetic Acid-Enhanced Multiphasic Hepatic Arterial Phase Imaging With Differential Subsampling With Cartesian Ordering.

    Science.gov (United States)

    Ichikawa, Shintaro; Motosugi, Utaroh; Oishi, Naoki; Shimizu, Tatsuya; Wakayama, Tetsuya; Enomoto, Nobuyuki; Matsuda, Masanori; Onishi, Hiroshi

    2018-04-01

    The aim of this study was to evaluate the efficacy of multiphasic hepatic arterial phase (HAP) imaging using DISCO (differential subsampling with Cartesian ordering) in increasing the confidence of diagnosis of hepatocellular carcinoma (HCC). This retrospective study was approved by the institutional review board, and the requirement for informed patient consent was waived. Consecutive patients (from 2 study periods) with malignant liver nodules were examined by gadoxetic acid-enhanced magnetic resonance imaging using either multiphasic (6 phases; n = 135) or single (n = 230) HAP imaging, which revealed 519 liver nodules other than benign ones (HCC, 497; cholangiocarcinoma, 11; metastases, 10; and malignant lymphoma, 1). All nodules were scored in accordance with the Liver Imaging Reporting and Data System (LI-RADS v2014), with or without consideration of ring-like enhancement in multiphasic HAP images as a major feature. In the multiphasic HAP group, 178 of 191 HCCs were scored as LR-3 to LR-5 (3 [1.69%], 85 [47.8%], and 90 [50.6%], respectively). Upon considering ring-like enhancement in multiphasic HAP images as a major feature, 5 more HCCs were scored as LR-5 (95 [53.4%]), which was a significantly more confident diagnosis than that with single HAP images (295 of 306 HCCs scored as LR-3 to LR-5: 13 [4.41%], 147 [49.8%], and 135 [45.8%], respectively; P = 0.0296). There was no significant difference in false-positive or false-negative diagnoses between the multiphasic and single HAP groups (P = 0.8400 and 0.1043, respectively). Multiphasic HAP imaging can improve the confidence of diagnosis of HCCs in gadoxetic acid-enhanced magnetic resonance imaging.

  10. Differential sensitivity of 5'UTR-NS5A recombinants of hepatitis C virus genotypes 1-6 to protease and NS5A inhibitors

    DEFF Research Database (Denmark)

    Li, Yi-Ping; Ramirez, Santseharay; Humes, Daryl

    2014-01-01

    BACKGROUND & AIMS: Hepatitis C virus (HCV) therapy will benefit from the preclinical evaluation of direct-acting antiviral (DAA) agents in infectious culture systems that test the effects on different virus genotypes. We developed HCV recombinants comprising the 5' untranslated region-NS5A (5-5A...... daclatasvir. The 1a(TN) 5-5A and JFH1-independent full-length viruses had similar levels of sensitivity to the DAA agents, validating the 5-5A recombinants as surrogates for full-length viruses in DAA testing. Compared with the 1a(TN) full-length virus, the 3a(S52) 5-5A recombinant was highly resistant to all...... protease inhibitors, and the 4a(ED43) recombinant was highly resistant to telaprevir and boceprevir, but most sensitive to other protease inhibitors. Compared with other protease inhibitors, MK-5172 had exceptional potency against all HCV genotypes. The NS5A inhibitor daclatasvir had the highest potency...

  11. The Faceted Discrete Growth and Phase Differentiation During the Directional Solidification of 20SiMnMo5 Steel

    Science.gov (United States)

    Ma, Xiaoping; Li, Dianzhong

    2018-03-01

    The microstructures, segregation and cooling curve were investigated in the directional solidification of 20SiMnMo5 steel. The typical characteristic of faceted growth is identified. The microstructures within the single cellular and within the single dendritic arm, together with the contradictive segregation distribution against the cooling curve, verify the discrete crystal growth in multi-scales. Not only the single cellular/dendritic arm but also the single martensite zone within the single cellular/dendritic arm is produced by the discrete growth. In the viewpoint of segregation, the basic domain following continuous growth has not been revealed. Along with the multi-scale faceted discrete growth, the phase differentiation happens for both the solid and liquid. The differentiated liquid phases appear and evolve with different sizes, positions, compositions and durations. The physical mechanism for the faceted discrete growth is qualitatively established based on the nucleation of new faceted steps induced by the composition gradient and temperature gradient.

  12. The Faceted Discrete Growth and Phase Differentiation During the Directional Solidification of 20SiMnMo5 Steel

    Science.gov (United States)

    Ma, Xiaoping; Li, Dianzhong

    2018-07-01

    The microstructures, segregation and cooling curve were investigated in the directional solidification of 20SiMnMo5 steel. The typical characteristic of faceted growth is identified. The microstructures within the single cellular and within the single dendritic arm, together with the contradictive segregation distribution against the cooling curve, verify the discrete crystal growth in multi-scales. Not only the single cellular/dendritic arm but also the single martensite zone within the single cellular/dendritic arm is produced by the discrete growth. In the viewpoint of segregation, the basic domain following continuous growth has not been revealed. Along with the multi-scale faceted discrete growth, the phase differentiation happens for both the solid and liquid. The differentiated liquid phases appear and evolve with different sizes, positions, compositions and durations. The physical mechanism for the faceted discrete growth is qualitatively established based on the nucleation of new faceted steps induced by the composition gradient and temperature gradient.

  13. Differential contribution of visual and auditory information to accurately predict the direction and rotational motion of a visual stimulus.

    Science.gov (United States)

    Park, Seoung Hoon; Kim, Seonjin; Kwon, MinHyuk; Christou, Evangelos A

    2016-03-01

    Vision and auditory information are critical for perception and to enhance the ability of an individual to respond accurately to a stimulus. However, it is unknown whether visual and auditory information contribute differentially to identify the direction and rotational motion of the stimulus. The purpose of this study was to determine the ability of an individual to accurately predict the direction and rotational motion of the stimulus based on visual and auditory information. In this study, we recruited 9 expert table-tennis players and used table-tennis service as our experimental model. Participants watched recorded services with different levels of visual and auditory information. The goal was to anticipate the direction of the service (left or right) and the rotational motion of service (topspin, sidespin, or cut). We recorded their responses and quantified the following outcomes: (i) directional accuracy and (ii) rotational motion accuracy. The response accuracy was the accurate predictions relative to the total number of trials. The ability of the participants to predict the direction of the service accurately increased with additional visual information but not with auditory information. In contrast, the ability of the participants to predict the rotational motion of the service accurately increased with the addition of auditory information to visual information but not with additional visual information alone. In conclusion, this finding demonstrates that visual information enhances the ability of an individual to accurately predict the direction of the stimulus, whereas additional auditory information enhances the ability of an individual to accurately predict the rotational motion of stimulus.

  14. Directed Differentiation of Human-Induced Pluripotent Stem Cells to Mesenchymal Stem Cells.

    Science.gov (United States)

    Lian, Qizhou; Zhang, Yuelin; Liang, Xiaoting; Gao, Fei; Tse, Hung-Fat

    2016-01-01

    Multipotent stromal cells, also known as mesenchymal stem cells (MSCs), possess great potential to generate a wide range of cell types including endothelial cells, smooth muscle cells, bone, cartilage, and lipid cells. This protocol describes in detail how to perform highly efficient, lineage-specific differentiation of human-induced pluripotent stem cells (iPSCs) with an MSCs fate. The approach uses a clinically compliant protocol with chemically defined media, feeder-free conditions, and a CD105 positive and CD24 negative selection to achieve a single cell-based MSCs derivation from differentiating human pluripotent cells in approximately 20 days. Cells generated with this protocol express typical MSCs surface markers and undergo adipogenesis, osteogenesis, and chondrogenesis similar to adult bone marrow-derived MSCs (BM-MSCs). Nonetheless, compared with adult BM-MSCs, iPSC-MSCs display a higher proliferative capacity, up to 120 passages, without obvious loss of self-renewal potential and constitutively express MSCs surface antigens. MSCs generated with this protocol have numerous applications, including expansion to large scale cell numbers for tissue engineering and the development of cellular therapeutics. This approach has been used to rescue limb ischemia, allergic disorders, and cigarette smoke-induced lung damage and to model mesenchymal and vascular disorders of Hutchinson-Gilford progeria syndrome (HGPS).

  15. SHP1 Regulates Bone Mass by Directing Mesenchymal Stem Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Menghui Jiang

    2016-07-01

    Full Text Available Osteoblasts and adipocytes are derived from a common precursor, mesenchymal stem cells (MSCs. Alterations in the normal fate of differentiating MSCs are involved in the development of obesity and osteoporosis. Here, we report that viable motheaten (mev mice, which are deficient in the SH2-domain-containing phosphatase-1 (SHP1, develop osteoporosis spontaneously. Consistently, MSCs from mev/mev mice exhibit significantly reduced osteogenic potential and greatly increased adipogenic potential. When MSCs were transplanted into nude mice, SHP1-deficient MSCs resulted in diminished bone formation compared with wild-type MSCs. SHP1 was found to bind to GSK3β and suppress its kinase activity by dephosphorylating pY216, thus resulting in β-catenin stabilization. Mice, in which SHP1 was deleted in MSCs using SHP1fl/flDermo1-cre, displayed significantly decreased bone mass and increased adipose tissue. Taken together, these results suggest a possible role for SHP1 in controlling tissue homeostasis through modulation of MSC differentiation via Wnt signaling regulation.

  16. The relative contribution of paracine effect versus direct differentiation on adipose-derived stem cell transplantation mediated cardiac repair.

    Directory of Open Access Journals (Sweden)

    Dezhong Yang

    Full Text Available BACKGROUND: Recent studies have demonstrated that transplantation of adipose-derived stem cell (ADSC can improve cardiac function in animal models of myocardial infarction (MI. However, the mechanisms underlying the beneficial effect are not fully understood. In this study, we characterized the paracrine effect of transplanted ADSC and investigated its relative importance versus direct differentiation in ADSC transplantation mediated cardiac repair. METHODOLOGY/PRINCIPAL FINDINGS: MI was experimentally induced in mice by ligation of the left anterior descending coronary artery. Either human ADSC, conditioned medium (CM collected from the same amount of ADSC or control medium was injected into the peri-infarct region immediately after MI. Compared with the control group, both ADSC and ADSC-CM significantly reduced myocardial infarct size and improved cardiac function. The therapeutic efficacy of ADSC was moderately superior to ADSC-CM. ADSC-CM significantly reduced cardiomyocyte apoptosis in the infarct border zone, to a similar degree with ADSC treatment. ADSC enhanced angiogenesis in the infarct border zone, but to a stronger degree than that seen in the ADSC-CM treatment. ADSC was able to differentiate to endothelial cell and smooth muscle cell in post-MI heart; these ADSC-derived vascular cells amount to about 9% of the enhanced angiogenesis. No cardiomyocyte differentiated from ADSC was found. CONCLUSIONS: ADSC-CM is sufficient to improve cardiac function of infarcted hearts. The therapeutic function of ADSC transplantation is mainly induced by paracrine-mediated cardioprotection and angiogenesis, while ADSC differentiation contributes a minor benefit by being involved in angiogenesis. Highlights 1 ADSC-CM is sufficient to exert a therapeutic potential. 2. ADSC was able to differentiate to vascular cells but not cardiomyocyte. 3. ADSC derived vascular cells amount to about 9% of the enhanced angiogenesis. 4. Paracrine effect is the major

  17. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA.

    Science.gov (United States)

    Warren, Luigi; Manos, Philip D; Ahfeldt, Tim; Loh, Yuin-Han; Li, Hu; Lau, Frank; Ebina, Wataru; Mandal, Pankaj K; Smith, Zachary D; Meissner, Alexander; Daley, George Q; Brack, Andrew S; Collins, James J; Cowan, Chad; Schlaeger, Thorsten M; Rossi, Derrick J

    2010-11-05

    Clinical application of induced pluripotent stem cells (iPSCs) is limited by the low efficiency of iPSC derivation and the fact that most protocols modify the genome to effect cellular reprogramming. Moreover, safe and effective means of directing the fate of patient-specific iPSCs toward clinically useful cell types are lacking. Here we describe a simple, nonintegrating strategy for reprogramming cell fate based on administration of synthetic mRNA modified to overcome innate antiviral responses. We show that this approach can reprogram multiple human cell types to pluripotency with efficiencies that greatly surpass established protocols. We further show that the same technology can be used to efficiently direct the differentiation of RNA-induced pluripotent stem cells (RiPSCs) into terminally differentiated myogenic cells. This technology represents a safe, efficient strategy for somatic cell reprogramming and directing cell fate that has broad applicability for basic research, disease modeling, and regenerative medicine. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Value and innovation of direct-acting antivirals: long-term health outcomes of the strategic plan for the management of hepatitis C in Spain.

    Science.gov (United States)

    Turnes, Juan; Domínguez-Hernández, Raquel; Casado, Miguel Ángel

    2017-12-01

    To assess the long-term healthcare costs and health outcomes in association with the access to new direct-acting antivirals (DAAs), during the first year of the National Strategic Plan for Chronic Hepatitis C (SPCHC) in patients with chronic hepatitis C (CHC) in Spain. A decision tree and a lifetime Markov model were developed to simulate the natural history, morbidity, and mortality of a cohort of 51,900 patients with CHC before (pre-DAA strategy) and after (post-DAA strategy) access to DAAs, following SPCHC approval. The percentage of patients treated, transition probabilities, disease management costs, health state utility values, sustained virologic response rates and treatment costs were obtained from the literature and published data from Spain. The results were expressed in terms of costs (€, 2016), quality-adjusted life years (QALYs) and prevention of clinical events, with an annual discount rate of 3%. The post-DAA strategy would prevent 8,667 cases of decompensated cirrhosis, 5,471 cases of hepatocellular carcinoma, 1,137 liver transplants and 9,608 liver-related deaths. The cohort of 51,900 patients would require investments of 1,606 and 1,230 million euros with the post-DAA and pre-DAA strategies, respectively. This would produce 819,674 and 665,703 QALYs. The use of new DAA-based treatments in CHC patients during the first year after the implementation of the SPCHC significantly reduced long-term morbidity and mortality and increased quality of life; demonstrating that this plan is an efficient use of public health resources.

  19. Differential diagnosis and management of human-directed aggression in cats.

    Science.gov (United States)

    Frank, Diane; Dehasse, Joel

    2003-03-01

    Human-directed aggression in cats should be evaluated as a multifactorial problem. It results from the combined actions of heredity, environment, learning, human social requirements (or needs), client interactions, lack of understanding of normal feline behavior, unrealistic client expectations, and lack of meeting the cat's basic ethologic needs. Managing human-directed aggression in cats encompasses the use of environmental modification, therapies, and, when and if needed, regulatory drugs so as to increase learning capabilities and adaptation and decrease danger to the human victims.

  20. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... friend, spouse, life partner, parent, sibling or other family member. What is HE? Hepatic Encephalopathy, sometimes referred ... disease is. It’s important for you and your family to become familiar with the signs of Hepatic ...

  1. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Your Story Spread the Word Give While You Shop Contact Us Donate Now Hepatic Encephalopathy Back Hepatic ... Your Story Spread the Word Give While You Shop Contact Us Donate Now Help ALF Improve This ...

  2. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Now Hepatic Encephalopathy Back Hepatic Encephalopathy is a brain disorder that develops in some individuals with liver ... is a condition that causes temporary worsening of brain function in people with advanced liver disease. When ...

  3. Alcohol and Hepatitis

    Science.gov (United States)

    ... Home » Living with Hepatitis » Daily Living: Alcohol Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... heavy drinking, most heavy drinkers have developed cirrhosis. Hepatitis C and cirrhosis In general, someone with hepatitis ...

  4. Hepatitis C: Treatment

    Science.gov (United States)

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

  5. 2015 Philip S. Portoghese Medicinal Chemistry Lectureship. Curing Hepatitis C Virus Infection with Direct-Acting Antiviral Agents: The Arc of a Medicinal Chemistry Triumph.

    Science.gov (United States)

    Meanwell, Nicholas A

    2016-08-25

    The development of direct-acting antiviral agents that can cure a chronic hepatitis C virus (HCV) infection after 8-12 weeks of daily, well-tolerated therapy has revolutionized the treatment of this insidious disease. In this article, three of Bristol-Myers Squibb's HCV programs are summarized, each of which produced a clinical candidate: the NS3 protease inhibitor asunaprevir (64), marketed as Sunvepra, the NS5A replication complex inhibitor daclatasvir (117), marketed as Daklinza, and the allosteric NS5B polymerase inhibitor beclabuvir (142), which is in late stage clinical studies. A clinical study with 64 and 117 established for the first time that a chronic HCV infection could be cured by treatment with direct-acting antiviral agents alone in the absence of interferon. The development of small molecule HCV therapeutics, designed by medicinal chemists, has been hailed as "the arc of a medical triumph" but may equally well be described as "the arc of a medicinal chemistry triumph".

  6. A cross-sectional study of hepatitis E virus infection in healthy people directly exposed and unexposed to pigs in a rural community in northern Thailand.

    Science.gov (United States)

    Hinjoy, S; Nelson, K E; Gibbons, R V; Jarman, R G; Mongkolsirichaikul, D; Smithsuwan, P; Fernandez, S; Labrique, A B; Patchanee, P

    2013-12-01

    A cross-sectional study of the association between occupational pig exposure and hepatitis E virus (HEV) infection in adult pig farmers and the general population who were not directly exposed to pigs was conducted in Nan Province, Thailand, from November 2010 to April 2011. All participants were interviewed to provide information on their job history, eating habits and other potential confounders. The prevalence of anti-HEV immunoglobulin G antibodies (IgG) among 513 subjects was 23.0%. Hand washing with water and soap was associated with a lower seroprevalence of HEV infection, whereas living in an area with frequent flooding (OR 1.64, 95% CI: 1.00-2.68) and consuming internal pig organs more than twice per week (OR 3.23, 95%CI: 1.15-9.01) were both associated with a higher seroprevalence of anti-HEV IgG. There was no association between HEV seroprevalence and frequent, direct occupational pig contact. © 2012 Blackwell Verlag GmbH.

  7. Differential and directional effects of perfusion on electrical and thermal conductivities in liver.

    Science.gov (United States)

    Podhajsky, Ronald J; Yi, Ming; Mahajan, Roop L

    2009-01-01

    Two different measurement probes--an electrical probe and a thermal conductivity probe--were designed, fabricated, calibrated, and used in experimental studies on a pig liver model that was designed to control perfusion rates. These probes were fabricated by photolithography and mounted in 1.5-mm diameter catheters. We measured the local impedance and thermal conductivity, respectively, of the artificially perfused liver at different flow rates and, by rotating the probes, in different directions. The results show that both the local electrical conductivity and the thermal conductivity varied location to location, that thermal conductivity increased with decreased distance to large blood vessels, and that significant directional differences exist in both electrical and thermal conductivities. Measurements at different perfusion rates demonstrated that both the local electrical and local thermal conductivities increased linearly with the square root of perfusion rate. These correlations may be of great value to many energy-based biomedical applications.

  8. Hepatitis C

    Science.gov (United States)

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

  9. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Caregiver Support Caregiver Stories Home › What is Hepatic Encephalopathy? Why Your Liver is Important The Connection Between HE and Liver ... Why it’s Important to Treat HE Symptoms of Liver Failure Glossary of terms ... is Hepatic Encephalopathy? Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy ...

  10. Hepatic Encephalopathy

    Science.gov (United States)

    ... Caregiver Support Caregiver Stories Home › What is Hepatic Encephalopathy? Why Your Liver is Important The Connection Between HE and Liver ... Why it’s Important to Treat HE Symptoms of Liver Failure Glossary of terms ... is Hepatic Encephalopathy? Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy ...

  11. Hepatitis A

    Science.gov (United States)

    ... is an inflammation of the liver. One type, hepatitis A, is caused by the hepatitis A virus (HAV). The disease spreads through contact with ... suggest medicines to help relieve your symptoms. The hepatitis A vaccine can prevent HAV. Good hygiene can also ...

  12. Differential plasma microRNA profiles in HBeAg positive and HBeAg negative children with chronic hepatitis B

    DEFF Research Database (Denmark)

    Winther, Thilde Nordmann; Bang-Berthelsen, Claus Heiner; Heiberg, Ida Louise

    2013-01-01

    Children chronically infected with hepatitis B virus (HBV) are at high risk of progressive liver disease. However, no treatment is available that is consistently effective in curing chronic hepatitis B (CHB) in children. Improved understanding of the natural course of disease is warranted....... Identification of specific microRNA (miRNA) profiles in children chronically infected with HBV may provide insight into the pathogenesis of CHB and lead to advances in the management of children with CHB....

  13. Expression of Hepcidin and Growth Differentiation Factor 15 (GDF-15 Levels in Thalassemia Patients with Iron Overload and Positive Anti Hepatitis C Virus

    Directory of Open Access Journals (Sweden)

    Nuri Dyah Indrasari

    2016-09-01

    Full Text Available Background: Thalassemia patients who undergo life-long recurrent blood transfusion will experience iron overload in various organs including the liver and possibly suffer from chronic hepatitis C infection which may lead to liver impairment. The liver produces hepcidin, a hormone which plays role in the regulation of iron level in the blood. Various factors may influence hepcidin level in the blood. Chronic hepatitis C causes iron overload and liver impairment. Liver impairment and haemolytic anaemia due to haemoglobinopathy will suppress hepcidin production. Anaemia stimulates growth differentiation factor 15 (GDF-15 to increase erythropoiesis and suppress hepcidin production. Iron overload causes increase in hepcidin level. Presence of factors which decrease or increase hepcidin production will express various levels of hepcidin. This study aimed to identify the expression of hepcidin and GDF-15 levels in thalassemia patients with iron overload and positive anti-HCV. Information on hepcidin and GDF-15 levels are beneficial in the management of iron overload in thalassemia with positive anti-HCV. Method: This study was a descriptive analytic study in thalassemia patients who had received recurrent blood transfusion ≥ 12 times, suffered from iron overload (transferrin saturation > 55% and ferritin > 1,000 ng/mL, which consisted of 31 individuals with positive anti-HCV and 27 individuals with negative anti-HCV. This study was performed in Thalassemia Centre Department of Child Health and Department of Clinical Pathology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, in October 2011–January 2012. Serum hepcidin and GDF-15 examinations were performed using enzyme-linked immunosorbent assay (ELISA method. Aspartate aminotransferase (AST and alanine aminotransferase (ALT examinations were performed using colorimetry method. Data on ferritin and transferrin saturation were obtained from medical records in the last 3

  14. A Tat-conjugated Peptide Nucleic Acid Tat-PNA-DR Inhibits Hepatitis B Virus Replication In Vitro and In Vivo by Targeting LTR Direct Repeats of HBV RNA

    Science.gov (United States)

    Zeng, Zhengyang; Han, Shisong; Hong, Wei; Lang, Yange; Li, Fangfang; Liu, Yongxiang; Li, Zeyong; Wu, Yingliang; Li, Wenxin; Zhang, Xianzheng; Cao, Zhijian

    2016-01-01

    Hepatitis B virus (HBV) infection is a major cause of chronic active hepatitis, cirrhosis, and primary hepatocellular carcinoma, all of which are severe threats to human health. However, current clinical therapies for HBV are limited by potential side effects, toxicity, and drug-resistance. In this study, a cell-penetrating peptide-conjugated peptide nucleic acid (PNA), Tat-PNA-DR, was designed to target the direct repeat (DR) sequences of HBV. Tat-PNA-DR effectively inhibited HBV replication in HepG2.2.15 cells. Its anti-HBV effect relied on the binding of Tat-PNA-DR to the DR, whereby it suppressed the translation of hepatitis B e antigen (HBeAg), HBsAg, HBV core, hepatitis B virus x protein, and HBV reverse transcriptase (RT) and the reverse transcription of the HBV genome. Furthermore, Tat-PNA-DR administered by intravenous injection efficiently cleared HBeAg and HBsAg in an acute hepatitis B mouse model. Importantly, it induced an 80% decline in HBV DNA in mouse serum, which was similar to the effect of the widely used clinical drug Lamivudine (3TC). Additionally, a long-term hydrodynamics HBV mouse model also demonstrated Tat-PNA-DR's antiviral effect. Interestingly, Tat-PNA-DR displayed low cytotoxicity, low mouse acute toxicity, low immunogenicity, and high serum stability. These data indicate that Tat-PNA-DR is a unique PNA and a promising drug candidate against HBV. PMID:26978579

  15. A Tat-conjugated Peptide Nucleic Acid Tat-PNA-DR Inhibits Hepatitis B Virus Replication In Vitro and In Vivo by Targeting LTR Direct Repeats of HBV RNA

    Directory of Open Access Journals (Sweden)

    Zhengyang Zeng

    2016-01-01

    Full Text Available Hepatitis B virus (HBV infection is a major cause of chronic active hepatitis, cirrhosis, and primary hepatocellular carcinoma, all of which are severe threats to human health. However, current clinical therapies for HBV are limited by potential side effects, toxicity, and drug-resistance. In this study, a cell-penetrating peptide-conjugated peptide nucleic acid (PNA, Tat-PNA-DR, was designed to target the direct repeat (DR sequences of HBV. Tat-PNA-DR effectively inhibited HBV replication in HepG2.2.15 cells. Its anti-HBV effect relied on the binding of Tat-PNA-DR to the DR, whereby it suppressed the translation of hepatitis B e antigen (HBeAg, HBsAg, HBV core, hepatitis B virus x protein, and HBV reverse transcriptase (RT and the reverse transcription of the HBV genome. Furthermore, Tat-PNA-DR administered by intravenous injection efficiently cleared HBeAg and HBsAg in an acute hepatitis B mouse model. Importantly, it induced an 80% decline in HBV DNA in mouse serum, which was similar to the effect of the widely used clinical drug Lamivudine (3TC. Additionally, a long-term hydrodynamics HBV mouse model also demonstrated Tat-PNA-DR's antiviral effect. Interestingly, Tat-PNA-DR displayed low cytotoxicity, low mouse acute toxicity, low immunogenicity, and high serum stability. These data indicate that Tat-PNA-DR is a unique PNA and a promising drug candidate against HBV.

  16. MASTR directs MyoD-dependent satellite cell differentiation during skeletal muscle regeneration

    Science.gov (United States)

    Mokalled, Mayssa H.; Johnson, Aaron N.; Creemers, Esther E.; Olson, Eric N.

    2012-01-01

    In response to skeletal muscle injury, satellite cells, which function as a myogenic stem cell population, become activated, expand through proliferation, and ultimately fuse with each other and with damaged myofibers to promote muscle regeneration. Here, we show that members of the Myocardin family of transcriptional coactivators, MASTR and MRTF-A, are up-regulated in satellite cells in response to skeletal muscle injury and muscular dystrophy. Global and satellite cell-specific deletion of MASTR in mice impairs skeletal muscle regeneration. This impairment is substantially greater when MRTF-A is also deleted and is due to aberrant differentiation and excessive proliferation of satellite cells. These abnormalities mimic those associated with genetic deletion of MyoD, a master regulator of myogenesis, which is down-regulated in the absence of MASTR and MRTF-A. Consistent with an essential role of MASTR in transcriptional regulation of MyoD expression, MASTR activates a muscle-specific postnatal MyoD enhancer through associations with MEF2 and members of the Myocardin family. Our results provide new insights into the genetic circuitry of muscle regeneration and identify MASTR as a central regulator of this process. PMID:22279050

  17. Specific Intensity Direct Current (DC) Electric Field Improves Neural Stem Cell Migration and Enhances Differentiation towards βIII-Tubulin+ Neurons

    Science.gov (United States)

    Zhao, Huiping; Steiger, Amanda; Nohner, Mitch; Ye, Hui

    2015-01-01

    Control of stem cell migration and differentiation is vital for efficient stem cell therapy. Literature reporting electric field–guided migration and differentiation is emerging. However, it is unknown if a field that causes cell migration is also capable of guiding cell differentiation—and the mechanisms for these processes remain unclear. Here, we report that a 115 V/m direct current (DC) electric field can induce directional migration of neural precursor cells (NPCs). Whole cell patching revealed that the cell membrane depolarized in the electric field, and buffering of extracellular calcium via EGTA prevented cell migration under these conditions. Immunocytochemical staining indicated that the same electric intensity could also be used to enhance differentiation and increase the percentage of cell differentiation into neurons, but not astrocytes and oligodendrocytes. The results indicate that DC electric field of this specific intensity is capable of promoting cell directional migration and orchestrating functional differentiation, suggestively mediated by calcium influx during DC field exposure. PMID:26068466

  18. Experimental approaches for distribution and behavior of water in PEMFC under flow direction and differential pressure using neutron imaging technique

    International Nuclear Information System (INIS)

    Kim, TaeJoo; Kim, JongRok; Sim, CheulMuu; Lee, SeungWook; Kaviany, Massound; Son, SangYoung; Kim, MooHwan

    2009-01-01

    In this investigation, we prepared a 3-parallel serpentine single PEMFC which has an active area of 25 cm 2 and a flow channel cross section of 1x1 mm. Distribution and transport of water in an operating PEMFC were observed by varying the flow directions (co-current and counter-current) in each channel and the differential pressures (100, 200, 300 kPa) applied between the anode and cathode channels. This investigation was performed at the neutron imaging facility at the NIST of which the collimation ratio and neutron fluence rate are 600, 7.2x10 6 n/s/cm 2 , respectively. Neutron image was continuously recorded by an amorphous silicon flat panel detector every 1 s during the operation of the fuel cell. It has been observed that the differential pressure affects the total amount of water produced while the flow direction affects the spatial distribution of water when the neutron images were analyzed for several different operating conditions. More specifically, the amount of water production in the fuel cell increased as the partial pressure increases at a given current density and the water production was more uniform for the counter current than the co-current case. It is shown that the neutron imaging technique is a powerful tool to visualize the PEMFC. The information on the water distribution and behavior at an operating PEMFC helps improve the efficiency of PEMFC.

  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. Differential Timing of Spider Mite-Induced Direct and Indirect Defenses in Tomato Plants1[w

    Science.gov (United States)

    Kant, Merijn R.; Ament, Kai; Sabelis, Maurice W.; Haring, Michel A.; Schuurink, Robert C.

    2004-01-01

    Through a combined metabolomics and transcriptomics approach we analyzed the events that took place during the first 5 d of infesting intact tomato (Lycopersicon esculentum) plants with spider mites (Tetranychus urticae). Although the spider mites had caused little visible damage to the leaves after 1 d, they had already induced direct defense responses. For example, proteinase inhibitor activity had doubled and the transcription of genes involved in jasmonate-, salicylate-, and ethylene-regulated defenses had been activated. On day four, proteinase inhibitor activity and particularly transcript levels of salicylate-regulated genes were still maintained. In addition, genes involved in phospholipid metabolism were up-regulated on day one and those in the secondary metabolism on day four. Although transcriptional up-regulation of the enzymes involved in the biosynthesis of monoterpenes and diterpenes already occurred on day one, a significant increase in the emission of volatile terpenoids was delayed until day four. This increase in volatile production coincided with the increased olfactory preference of predatory mites (Phytoseiulus persimilis) for infested plants. Our results indicate that tomato activates its indirect defenses (volatile production) to complement the direct defense response against spider mites. PMID:15122016

  1. Differential coding of reward and movement information in the dorsomedial striatal direct and indirect pathways.

    Science.gov (United States)

    Shin, Jung Hwan; Kim, Dohoung; Jung, Min Whan

    2018-01-26

    The direct and indirect pathways of the basal ganglia have long been thought to mediate behavioral promotion and inhibition, respectively. However, this classic dichotomous model has been recently challenged. To better understand neural processes underlying reward-based learning and movement control, we recorded from direct (dSPNs) and indirect (iSPNs) pathway spiny projection neurons in the dorsomedial striatum of D1-Cre and D2-Cre mice performing a probabilistic Pavlovian conditioning task. dSPNs tend to increase activity while iSPNs decrease activity as a function of reward value, suggesting the striatum represents value in the relative activity levels of dSPNs versus iSPNs. Lick offset-related activity increase is largely dSPN selective, suggesting dSPN involvement in suppressing ongoing licking behavior. Rapid responses to negative outcome and previous reward-related responses are more frequent among iSPNs than dSPNs, suggesting stronger contributions of iSPNs to outcome-dependent behavioral adjustment. These findings provide new insights into striatal neural circuit operations.

  2. A simple bedside blood test (Fibrofast; FIB-5) is superior to FIB-4 index for the differentiation between non-significant and significant fibrosis in patients with chronic hepatitis C.

    Science.gov (United States)

    Shiha, G; Seif, S; Eldesoky, A; Elbasiony, M; Soliman, R; Metwally, A; Zalata, K; Mikhail, N

    2017-05-01

    A simple non-invasive score (Fibrofast, FIB-5) was developed using five routine laboratory tests (ALT, AST, alkaline phosphatase, albumin and platelets count) for the detection of significant hepatic fibrosis in patients with chronic hepatitis C. The FIB-4 index is a non-invasive test for the assessment of liver fibrosis, and a score of ≤1.45 enables the correct identification of patients who have non-significant (F0-1) from significant fibrosis (F2-4), and could avoid liver biopsy. The aim of this study was to compare the performance characteristics of FIB-5 and FIB-4 to differentiate between non-significant and significant fibrosis. A cross-sectional study included 604 chronic HCV patients. All liver biopsies were scored using the METAVIR system. Both FIB-5 and FIB-4 scores were measured and the performance characteristics were calculated using the ROC curve. The performance characteristics of FIB-5 at ≥7.5 and FIB-4 at ≤1.45 for the differentiation between non-significant fibrosis and significant fibrosis were: specificity 94.4%, PPV 85.7%, and specificity 54.9%, PPV 55.7% respectively. FIB-5 score at the new cutoff is superior to FIB-4 index for the differentiation between non-significant and significant fibrosis.

  3. Bioreactor systems for tissue engineering II. Strategies for the expansion and directed differentiation of stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Kasper, Cornelia [Hannover Univ. (Germany). Inst. fuer Technische Chemie; Griensven, Martijn van [Ludwig Boltzmann Institut fuer Klinische und Experimentelle Traumatologie, Wien (Austria); Poertner, Ralf (eds.) [Technische Univ. Hamburg-Harburg (Germany). Inst. Biotechnologie und Verfahrenstechnik

    2010-07-01

    Alternative Sources of Adult Stem Cells: Human Amniotic Membrane, by S. Wolbank, M. van Griensven, R. Grillari-Voglauer, and A. Peterbauer-Scherb; - Mesenchymal Stromal Cells Derived from Human Umbilical Cord Tissues: Primitive Cells with Potential for Clinical and Tissue Engineering Applications, by P. Moretti, T. Hatlapatka, D. Marten, A. Lavrentieva, I. Majore, R. Hass and C. Kasper; - Isolation, Characterization, Differentiation, and Application of Adipose-Derived Stem Cells, by J. W. Kuhbier, B. Weyand, C. Radtke, P. M. Vogt, C. Kasper and K. Reimers; - Induced Pluripotent Stem Cells: Characteristics and Perspectives, by T. Cantz and U. Martin; - Induced Pluripotent Stem Cell Technology in Regenerative Medicine and Biology, by D. Pei, J. Xu, Q. Zhuang, H.-F. Tse and M. A. Esteban; - Production Process for Stem Cell Based Therapeutic Implants: Expansion of the Production Cell Line and Cultivation of Encapsulated Cells, by C. Weber, S. Pohl, R. Poertner, P. Pino-Grace, D. Freimark, C. Wallrapp, P. Geigle and P. Czermak; - Cartilage Engineering from Mesenchymal Stem Cells, by C. Goepfert, A. Slobodianski, A.F. Schilling, P. Adamietz and R. Poertner; - Outgrowth Endothelial Cells: Sources, Characteristics and Potential Applications in Tissue Engineering and Regenerative Medicine, by S. Fuchs, E. Dohle, M. Kolbe, C. J. Kirkpatrick; - Basic Science and Clinical Application of Stem Cells in Veterinary Medicine, by I. Ribitsch, J. Burk, U. Delling, C. Geissler, C. Gittel, H. Juelke, W. Brehm; - Bone Marrow Stem Cells in Clinical Application: Harnessing Paracrine Roles and Niche Mechanisms, by R. M. El Backly, R. Cancedda; - Clinical Application of Stem Cells in the Cardiovascular System, C. Stamm, K. Klose, Y.-H. Choi. (orig.)

  4. Longitudinal bone growth is impaired by direct involvement of caffeine with chondrocyte differentiation in the growth plate.

    Science.gov (United States)

    Choi, Hyeonhae; Choi, Yuri; Kim, Jisook; Bae, Jaeman; Roh, Jaesook

    2017-01-01

    We showed previously that caffeine adversely affects longitudinal bone growth and disrupts the histomorphometry of the growth plate during the pubertal growth spurt. However, little attention has been paid to the direct effects of caffeine on chondrocytes. Here, we investigated the direct effects of caffeine on chondrocytes of the growth plate in vivo and in vitro using a rapidly growing young rat model, and determined whether they were related to the adenosine receptor signaling pathway. A total of 15 male rats (21 days old) were divided randomly into three groups: a control group and two groups fed caffeine via gavage with 120 and 180 mg kg -1  day -1 for 4 weeks. After sacrifice, the tibia processed for the analysis of the long bone growth and proliferation of chondrocytes using tetracycline and BrdU incorporation, respectively. Caffeine-fed animals showed decreases in matrix mineralization and proliferation rate of growth plate chondrocytes compared with the control. To evaluate whether caffeine directly affects chondrocyte proliferation and chondrogenic differentiation, primary rat chondrocytes were isolated from the growth plates and cultured in either the presence or absence of caffeine at concentrations of 0.1-1 mm, followed by determination of the cellular proliferation or expression profiles of cellular differentiation markers. Caffeine caused significant decreases in extracellular matrix production, mineralization, and alkaline phosphatase activity, accompanied with decreases in gene expression of the cartilage-specific matrix proteins such as aggrecan, type II collagen and type X. Our results clearly demonstrate that caffeine is capable of interfering with cartilage induction by directly inhibiting the synthetic activity and orderly expression of marker genes relevant to chondrocyte maturation. In addition, we found that the adenosine type 1 receptor signaling pathway may be partly involved in the detrimental effects of caffeine on chondrogenic

  5. Nonalcoholic fatty liver disease and hepatic cirrhosis: Comparison with viral hepatitis-associated steatosis.

    Science.gov (United States)

    Haga, Yuki; Kanda, Tatsuo; Sasaki, Reina; Nakamura, Masato; Nakamoto, Shingo; Yokosuka, Osamu

    2015-12-14

    Nonalcoholic fatty liver disease (NAFLD) including nonalcoholic steatohepatitis (NASH) is globally increasing and has become a world-wide health problem. Chronic infection with hepatitis B virus or hepatitis C virus (HCV) is associated with hepatic steatosis. Viral hepatitis-associated hepatic steatosis is often caused by metabolic syndrome including obesity, type 2 diabetes mellitus and/or dyslipidemia. It has been reported that HCV genotype 3 exerts direct metabolic effects that lead to hepatic steatosis. In this review, the differences between NAFLD/NASH and viral hepatitis-associated steatosis are discussed.

  6. Differential involvement of IL-6 in the early and late phase of 1-methylnicotinamide (MNA) release in Concanavalin A-induced hepatitis.

    Science.gov (United States)

    Sternak, Magdalena; Jakubowski, Andrzej; Czarnowska, Elzbieta; Slominska, Ewa M; Smolenski, Ryszard T; Szafarz, Malgorzata; Walczak, Maria; Sitek, Barbara; Wojcik, Tomasz; Jasztal, Agnieszka; Kaminski, Karol; Chlopicki, Stefan

    2015-09-01

    Exogenous 1-methylnicotinamide (MNA) displays anti-inflammatory activity. The aim of this work was to characterize the profile of release of endogenous MNA during the initiation and progression of murine hepatitis induced by Concanavalin A (ConA). In particular we aimed to clarify the role of interleukin-6 (IL-6) as well as the energy state of hepatocytes in MNA release in early and late phases of ConA-induced hepatitis in mice. Hepatitis was induced by ConA in IL-6(+/+) and IL-6(-/-) mice, and various parameters of liver inflammation and injury, as well as the energy state of hepatocytes, were analysed in relation to MNA release. The decrease in ATP/ADP and NADH/NAD ratios, cytokine release (IL-6, IFN-ɤ), acute phase response (e.g. haptoglobin) and liver injury (alanine aminotransaminase, ALT) were all blunted in ConA-induced hepatitis in IL-6(-/-) mice as compared to IL-6(+/+) mice. The release of MNA in response to Con A was also significantly blunted in IL-6(-/-) mice as compared to IL-6(+/+) mice in the early stage of ConA-induced hepatitis. In turn, nicotinamide N-methyltransferase (NNMT) and aldehyde oxidase (AO) activities were blunted in the liver and MNA plasma concentration was elevated to similar degree in the late stage after Concanavalin A in IL-6(+/+) and IL-6(-/-) mice. In conclusion, we demonstrated that in ConA-induced hepatitis, early, but not late MNA release was IL-6-dependent. Our results suggest that in the initiation and early hepatitis, MNA release is linked to the energy deficit/impaired redox status in hepatocytes, while in a later phase, MNA release is rather linked to the systemic inflammation. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Differential presentation of endogenous and exogenous hepatitis B surface antigens influences priming of CD8(+) T cells in an epitope-specific manner.

    Science.gov (United States)

    Riedl, Petra; Reiser, Michael; Stifter, Katja; Krieger, Jana; Schirmbeck, Reinhold

    2014-07-01

    Little is known about whether presentation of endogenous and exogenous hepatitis B virus (HBV) surface antigens on APCs targeted by vaccination and/or virus-harboring hepatocytes influences de novo priming of CD8(+) T cells. We showed that surface antigen-expressing transfectants exclusively display a K(b) /S190 epitope, whereas cells pulsed with recombinant surface particles (rSPs) exclusively present a K(b) /S208 epitope to CD8(+) T cells. The differential presentation of these epitopes largely reflects the selective, but not exclusive, priming of K(b) /S190- and K(b) /S208-specific T cells in C57BL/6 mice by endogenous/DNA- or exogenous/protein-based vaccines, respectively. Silencing the K(b) /S190 epitope (K(b) /S190V194F ) in antigen-expressing vectors rescued the presentation of the K(b) /S208 epitope in stable transfectants and significantly enhanced priming of K(b) /S208-specific T cells in C57BL/6 mice. A K(b) /S190-mediated immunodominance operating in surface antigen-expressing cells, but not in rSP-pulsed cells, led to an efficient suppression in the presentation of the K(b) /S208 epitope and a consequent decrease in the priming of K(b) /S208-specific T cells. This K(b) /S190-mediated immunodominance also operated in 1.4HBV-S(mut) transgenic (tg) hepatocytes selectively expressing endogenous surface antigens and allowed priming of K(b) /S208- but not K(b) /S190-specific T cells in 1.4HBV-S(mut) tg mice. However, IFN-γ(+) K(b) /S208-specific T cells could not inhibit HBV replication in the liver of 1.4HBV-S(mut) tg mice. These results have practical implications for the design of T-cell-stimulating therapeutic vaccines. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Ethanol metabolism by alcohol dehydrogenase or cytochrome P450 2E1 differentially impairs hepatic protein trafficking and growth hormone signaling.

    Science.gov (United States)

    Doody, Erin E; Groebner, Jennifer L; Walker, Jetta R; Frizol, Brittnee M; Tuma, Dean J; Fernandez, David J; Tuma, Pamela L

    2017-12-01

    The liver metabolizes alcohol using alcohol dehydrogenase (ADH) and cytochrome P 450 2E1 (CYP2E1). Both enzymes metabolize ethanol into acetaldehyde, but CYP2E1 activity also results in the production of reactive oxygen species (ROS) that promote oxidative stress. We have previously shown that microtubules are hyperacetylated in ethanol-treated polarized, hepatic WIF-B cells and livers from ethanol-fed rats. We have also shown that enhanced protein acetylation correlates with impaired clathrin-mediated endocytosis, constitutive secretion, and nuclear translocation and that the defects are likely mediated by acetaldehyde. However, the roles of CYP2E1-generated metabolites and ROS in microtubule acetylation and these alcohol-induced impairments have not been examined. To determine if CYP2E1-mediated alcohol metabolism is required for enhanced acetylation and the trafficking defects, we coincubated cells with ethanol and diallyl sulfide (DAS; a CYP2E1 inhibitor) or N -acetyl cysteine (NAC; an antioxidant). Both agents failed to prevent microtubule hyperacetylation in ethanol-treated cells and also failed to prevent impaired secretion or clathrin-mediated endocytosis. Somewhat surprisingly, both DAS and NAC prevented impaired STAT5B nuclear translocation. Further examination of microtubule-independent steps of the pathway revealed that Jak2/STAT5B activation by growth hormone was prevented by DAS and NAC. These results were confirmed in ethanol-exposed HepG2 cells expressing only ADH or CYP2E1. Using quantitative RT-PCR, we further determined that ethanol exposure led to blunted growth hormone-mediated gene expression. In conclusion, we determined that alcohol-induced microtubule acetylation and associated defects in microtubule-dependent trafficking are mediated by ADH metabolism whereas impaired microtubule-independent Jak2/STAT5B activation is mediated by CYP2E1 activity. NEW & NOTEWORTHY Impaired growth hormone-mediated signaling is observed in ethanol

  9. Covalent growth factor tethering to direct neural stem cell differentiation and self-organization.

    Science.gov (United States)

    Ham, Trevor R; Farrag, Mahmoud; Leipzig, Nic D

    2017-04-15

    Tethered growth factors offer exciting new possibilities for guiding stem cell behavior. However, many of the current methods present substantial drawbacks which can limit their application and confound results. In this work, we developed a new method for the site-specific covalent immobilization of azide-tagged growth factors and investigated its utility in a model system for guiding neural stem cell (NSC) behavior. An engineered interferon-γ (IFN-γ) fusion protein was tagged with an N-terminal azide group, and immobilized to two different dibenzocyclooctyne-functionalized biomimetic polysaccharides (chitosan and hyaluronan). We successfully immobilized azide-tagged IFN-γ under a wide variety of reaction conditions, both in solution and to bulk hydrogels. To understand the interplay between surface chemistry and protein immobilization, we cultured primary rat NSCs on both materials and showed pronounced biological effects. Expectedly, immobilized IFN-γ increased neuronal differentiation on both materials. Expression of other lineage markers varied depending on the material, suggesting that the interplay of surface chemistry and protein immobilization plays a large role in nuanced cell behavior. We also investigated the bioactivity of immobilized IFN-γ in a 3D environment in vivo and found that it sparked the robust formation of neural tube-like structures from encapsulated NSCs. These findings support a wide range of potential uses for this approach and provide further evidence that adult NSCs are capable of self-organization when exposed to the proper microenvironment. For stem cells to be used effectively in regenerative medicine applications, they must be provided with the appropriate cues and microenvironment so that they integrate with existing tissue. This study explores a new method for guiding stem cell behavior: covalent growth factor tethering. We found that adding an N-terminal azide-tag to interferon-γ enabled stable and robust Cu-free 'click

  10. Hepatitis A through E (Viral Hepatitis)

    Science.gov (United States)

    ... Treatment Eating, Diet, & Nutrition Clinical Trials Wilson Disease Hepatitis (Viral) View or Print All Sections What is Viral Hepatitis? Viral hepatitis is an infection that causes liver inflammation ...

  11. Using geometric morphometric visualizations of directional selection gradients to investigate morphological differentiation.

    Science.gov (United States)

    Weaver, Timothy D; Gunz, Philipp

    2018-04-01

    Researchers studying extant and extinct taxa are often interested in identifying the evolutionary processes that have lead to the morphological differences among the taxa. Ideally, one could distinguish the influences of neutral evolutionary processes (genetic drift, mutation) from natural selection, and in situations for which selection is implicated, identify the targets of selection. The directional selection gradient is an effective tool for investigating evolutionary process, because it can relate form (size and shape) differences between taxa to the variation and covariation found within taxa. However, although most modern morphometric analyses use the tools of geometric morphometrics (GM) to analyze landmark data, to date, selection gradients have mainly been calculated from linear measurements. To address this methodological gap, here we present a GM approach for visualizing and comparing between-taxon selection gradients with each other, associated difference vectors, and "selection" gradients from neutral simulations. To exemplify our approach, we use a dataset of 347 three-dimensional landmarks and semilandmarks recorded on the crania of 260 primate specimens (112 humans, 67 common chimpanzees, 36 bonobos, 45 gorillas). Results on this example dataset show how incorporating geometric information can provide important insights into the evolution of the human braincase, and serve to demonstrate the utility of our approach for understanding morphological evolution. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

  12. The challenge of treating hepatitis C virus-associated cryoglobulinemic vasculitis in the era of anti-CD20 monoclonal antibodies and direct antiviral agents.

    Science.gov (United States)

    Roccatello, Dario; Sciascia, Savino; Rossi, Daniela; Solfietti, Laura; Fenoglio, Roberta; Menegatti, Elisa; Baldovino, Simone

    2017-06-20

    Mixed cryoglobulinemia syndrome (MC) is a systemic vasculitis involving kidneys, joints, skin, and peripheral nerves. While many autoimmune, lymphoproliferative, and neoplastic disorders have been associated with this disorder, hepatitis C virus (HCV) is known to be the etiologic agent in the majority of patients. Therefore, clinical research has focused on anti-viral drugs and, more recently, on the new, highly potent Direct-acting Antiviral Agents (DAAs). These drugs assure sustained virologic response (SVR) rates >90%. Nevertheless, data on their efficacy in patients with HCV-associated cryoglobulinemic vasculitis are disappointing, possibly due to the inability of the drugs to suppress the immune-mediated process once it has been triggered.Despite the potential risk of exacerbation of the infection, immunosuppression has traditionally been regarded as the first-line intervention in cryoglobulinemic vasculitis, especially if renal involvement is severe. Biologic agents have raised hopes for more manageable therapeutic approaches, and Rituximab (RTX), an anti CD20 monoclonal antibody, is the most widely used biologic drug. It has proved to be safer than conventional immunosuppressants, thus substantially changing the natural history of HCV-associated cryoglobulinemic vasculitis by providing long-term remission, especially with intensive regimens.The present review focuses on the new therapeutic opportunities offered by the combination of biological drugs, mainly Rituximab, with DAAs.

  13. State of the Art, Unresolved Issues, and Future Research Directions in the Fight against Hepatitis C Virus: Perspectives for Screening, Diagnostics of Resistances, and Immunization

    Directory of Open Access Journals (Sweden)

    Cecilia Trucchi

    2016-01-01

    Full Text Available Hepatitis C virus (HCV still represents a major public health threat, with a dramatic burden from both epidemiological and clinical points of view. New generation of direct-acting antiviral agents (DAAs has been recently introduced in clinical practice promising to cure HCV and to overcome the issues related to the interferon-based therapies. However, the emergence of drug resistance and the suboptimal activity of DAAs therapies against diverse HCV genotypes have been observed, determining treatment failure and hampering an effective control of HCV spread worldwide. Moreover, these treatments remain poorly accessible, particularly in low-income countries. Finally, effective screening strategy is crucial to early identifying and treating all HCV chronically infected patients. For all these reasons, even though new drugs may contribute to impacting HCV spread worldwide a preventive HCV vaccine remains a cornerstone in the road to significantly reduce the HCV spread globally, with the ultimate goal of its eradication. Advances in molecular vaccinology, together with a strong financial, political, and societal support, will enable reaching this fundamental success in the coming years. In this comprehensive review, the state of the art about these major topics in the fight against HCV and the future of research in these fields are discussed.

  14. Predictors Associated with Increase in Skeletal Muscle Mass after Sustained Virological Response in Chronic Hepatitis C Treated with Direct Acting Antivirals

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    Kazunori Yoh

    2017-10-01

    Full Text Available Aims: We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC patients undergoing interferon (IFN-free direct acting antivirals (DAAs therapy who achieved sustained virological response (SVR. Patients and methods: A total of 69 CHC patients treated with DAAs were analyzed. We compared the changes in skeletal muscle index (SMI using bio-impedance analysis at baseline and SMI at SVR. SMI was calculated as the sum of skeletal muscle mass in upper and lower extremities divided by height squared (cm2/m2. Further, we identified pretreatment parameters contributing to the increased SMI at SVR. Results: SMI in males at baseline ranged from 6.73 to 9.08 cm2/m2 (median, 7.65 cm2/m2, while that in females ranged from 4.45 to 7.27 cm2/m2 (median, 5.81 cm2/m2. At SVR, 36 patients (52.2% had increased SMI as compared with baseline. In the univariate analysis, age (p = 0.0392, hyaluronic acid (p = 0.0143, and branched-chain amino acid to tyrosine ratio (BTR (p = 0.0024 were significant pretreatment factors linked to increased SMI at SVR. In the multivariate analysis, only BTR was an independent predictor linked to the increased SMI at SVR (p = 0.0488. Conclusion: Pretreatment BTR level can be helpful for predicting increased SMI after SVR in CHC patients undergoing IFN-free DAAs therapy.

  15. Direct-acting antiviral agent efficacy and safety in renal transplant recipients with chronic hepatitis C virus infection: A PRISMA-compliant study.

    Science.gov (United States)

    Chen, Keliang; Lu, Pei; Song, Rijin; Zhang, Jiexiu; Tao, Rongzhen; Wang, Zijie; Zhang, Wei; Gu, Min

    2017-07-01

    The efficacy and safety of direct-acting antivirals (DAAs) for treating hepatitis C virus (HCV)-infected renal transplant recipients (RTRs) has not been determined. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials and assessed the quality of eligible studies using the Joanna Briggs Institute scale. DAA efficacy and safety were assessed using standard mean difference (SMD) with 95% confidence intervals (95%CIs). Six studies (360 RTRs) were included. Two hundred thirty six RTRs (98.3%) achieved sustained virological response within 12 weeks; HCV infection was cleared in 239 RTRs after 24-week treatment. Liver function differed significantly pre- and posttreatment (alanine aminotransferase, SMD: 0.96, 95%CIs: 0.65, 1.26; aspartate aminotransferase, SMD: 0.89, 95%CIs: 0.60, 1.18); allograft function pre- and posttreatment was not statistically different (serum creatinine, SMD: -0.13, 95%CIs: -0.38, 0.12; estimated glomerular filtration rate, SMD: 0.20, 95%CIs: -0.11, 0.51). General symptoms (fatigue nausea dizziness or headache) were the most common adverse events (AEs) (39.3%). Severe AEs, that is, anemia, portal vein thrombosis, and streptococcus bacteraemia and pneumonia, were present in 1.1%, 0.6%, and 1.1% of RTRs, respectively. Our findings suggest that DAAs are highly efficacious and safe for treating HCV-infected RTRs and without significant AE.

  16. Diagnostic value of liver scintigraphy in fulminant hepatitis and severe acute hepatitis

    International Nuclear Information System (INIS)

    Shiomi, Susumu; Ikeoka, Naoko; Minowa, Takami; Kuroki, Tetsuo; Harihara, Shigeyoshi; Yamamoto, Sukeo; Ochi, Hironobu; Monna, Takeyuki

    1985-01-01

    Liver scintigraphy was performed in 12 cases with fulminant hepatitis, in 8 cases with severe acute hepatitis and in 44 cases with acute hepatitis. Scintiphotoes of severe hepatitis showed reduction of liver size, marked visualization of the bone marrow and the spleen, so this pattern was useful to differentiate from acute hepatitis. Relative size of the liver calculated by A.L.I. (anterior liver index) showed significant reduction in severe hepatitis compared with that of acute hepatitis. Three of five patients with died of severe hepatitis showed high uptake in the lung and ribs, but none of fifteen patients with severe hepatitis who recovered showed the abnormal accumulation in the lung and in the ribs. (author)

  17. Chemometric brand differentiation of commercial spices using direct analysis in real time mass spectrometry.

    Science.gov (United States)

    Pavlovich, Matthew J; Dunn, Emily E; Hall, Adam B

    2016-05-15

    Commercial spices represent an emerging class of fuels for improvised explosives. Being able to classify such spices not only by type but also by brand would represent an important step in developing methods to analytically investigate these explosive compositions. Therefore, a combined ambient mass spectrometric/chemometric approach was developed to quickly and accurately classify commercial spices by brand. Direct analysis in real time mass spectrometry (DART-MS) was used to generate mass spectra for samples of black pepper, cayenne pepper, and turmeric, along with four different brands of cinnamon, all dissolved in methanol. Unsupervised learning techniques showed that the cinnamon samples clustered according to brand. Then, we used supervised machine learning algorithms to build chemometric models with a known training set and classified the brands of an unknown testing set of cinnamon samples. Ten independent runs of five-fold cross-validation showed that the training set error for the best-performing models (i.e., the linear discriminant and neural network models) was lower than 2%. The false-positive percentages for these models were 3% or lower, and the false-negative percentages were lower than 10%. In particular, the linear discriminant model perfectly classified the testing set with 0% error. Repeated iterations of training and testing gave similar results, demonstrating the reproducibility of these models. Chemometric models were able to classify the DART mass spectra of commercial cinnamon samples according to brand, with high specificity and low classification error. This method could easily be generalized to other classes of spices, and it could be applied to authenticating questioned commercial samples of spices or to examining evidence from improvised explosives. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Hepatitis Vaccines

    Directory of Open Access Journals (Sweden)

    Sina Ogholikhan

    2016-03-01

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

  19. Hepatitis Vaccines

    Science.gov (United States)

    Ogholikhan, Sina; Schwarz, Kathleen B.

    2016-01-01

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

  20. Direct-acting Antivirals in Kidney Transplant Patients: Successful Hepatitis C Treatment and Short Term Reduction in Urinary Protein/Creatinine Ratios

    Directory of Open Access Journals (Sweden)

    Michael R. Goetsch

    2017-09-01

    Full Text Available Introduction: The role of Hepatitis C Virus (HCV clearance in long-term kidney graft survival is unknown. In this study, we examined short-term trends of urinary protein/creatinine (P/C ratios in a cohort of HCV-infected kidney transplant recipients with stable graft function and treated with direct-acting antivirals (DAAs. Methods: We conducted a retrospective study of 19 kidney transplant patients with chronic HCV infection treated with DAAs at the University of Alabama at Birmingham 1917 Viral Hepatitis Clinic between January 2013 and June 2016. Markers of glomerular damage were assessed using average protein/creatinine (P/C ratios measured pre- and post-treatment. We also described treatment efficacy using sustained virologic response at 12 weeks post-HCV treatment (SVR12. Results: The median age of the 19 patients included was 59 years (Q1=58, Q3=64 at completion of treatment. Of these patients, 68% were African American, 32% were White and 63% were male. The median time between kidney transplant and initiation of DAA therapy was 2.25 years (Q1=0.79, Q3=3.79. Post-treatment P/C ratios (median=0.127, Q1=0.090, Q3=0.220 were significantly lower (p=0.01 than pre-treatment ratios (median=0.168, Q1=0.118, Q3=0.385. P/C ratios decreased in 14 of 19 patients (74% with median change of -0.072 (median percent change= -40%. Post-treatment eGFRs (median=58.9, Q1=48.9, Q3=72.3 were not significantly different (p=0.82 than the pre-treatment values (median=57.0, Q1=48.8, Q3=67.8. Conclusions: In this preliminary study, there was a statistically significant decrease in P/C ratios associated with HCV clearance, suggesting a potential role for DAAs in improving kidney graft survival. Larger cohort studies will be needed to assess the clinical and long-term benefits of DAAs in this special population of HCV infected patients.

  1. The angiographic demonstration of hepatic vein obstruction

    International Nuclear Information System (INIS)

    Zu Maoheng; Xu Hao; Li Guojun; Gu Yuming; Wei Ning; Wang Cheng; Xu Wei

    2004-01-01

    Objective: To evaluate the angiographic feature of hepatic vein obstruction. Methods Forty-five patients (male 23, female 22, age 9-54 years) suffered from hepatic vein obstruction. The inferior vena cavography and the hepatic venography were performed in all cases. Results: IVC was free in 37 patients with hepatic vein obstruction, both IVC and HV were obstructed in 8 patients. The local or long stenosis of IVC was found in 31 inferior vena cavography. The diameter of IVC was normal in 12 patients. The sign of membranous dome was found in hepatic vein orifice in 5 cases and in accessory hepatic vein orifice in 4 cases. Intrahepatic venous collaterals were found in 45 cases. Conclusion: Hepatic vein obstruction can be reproached primarily in inferior vena cavography, the membranous dome is a direct sign of membranous obstruction of HV and AHV in inferior vena cavography. The selected hepatic venography can provide reliable evidence to diagnose hepatic vein obstruction

  2. Differential modulation of corticospinal excitability by different current densities of anodal transcranial direct current stimulation.

    Directory of Open Access Journals (Sweden)

    Andisheh Bastani

    Full Text Available BACKGROUND: Novel non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS have been developed in recent years. TDCS-induced corticospinal excitability changes depend on two important factors current intensity and stimulation duration. Despite clinical success with existing tDCS parameters, optimal protocols are still not entirely set. OBJECTIVE/HYPOTHESIS: The current study aimed to investigate the effects of four different anodal tDCS (a-tDCS current densities on corticospinal excitability. METHODS: Four current intensities of 0.3, 0.7, 1.4 and 2 mA resulting in current densities (CDs of 0.013, 0.029, 0.058 and 0.083 mA/cm(2 were applied on twelve right-handed (mean age 34.5±10.32 yrs healthy individuals in different sessions at least 48 hours apart. a-tDCS was applied continuously for 10 minute, with constant active and reference electrode sizes of 24 and 35 cm(2 respectively. The corticospinal excitability of the extensor carpi radialis muscle (ECR was measured before and immediately after the intervention and at 10, 20 and 30 minutes thereafter. RESULTS: Post hoc comparisons showed significant differences in corticospinal excitability changes for CDs of 0.013 mA/cm(2 and 0.029 mA/cm(2 (P = 0.003. There were no significant differences between excitability changes for the 0.013 mA/cm(2 and 0.058 mA/cm(2 (P = 0.080 or 0.013 mA/cm(2 and 0.083 mA/cm(2 (P = 0.484 conditions. CONCLUSION: This study found that a-tDCS with a current density of 0.013 mA/cm(2 induces significantly larger corticospinal excitability changes than CDs of 0.029 mA/cm(2. The implication is that might help to avoid applying unwanted amount of current to the cortical areas.

  3. Long-Term Follow-Up of Resistance-Associated Substitutions in Hepatitis C Virus in Patients in Which Direct Acting Antiviral-Based Therapy Failed.

    Science.gov (United States)

    Yoshida, Kanako; Hai, Hoang; Tamori, Akihiro; Teranishi, Yuga; Kozuka, Ritsuzo; Motoyama, Hiroyuki; Kawamura, Etsushi; Hagihara, Atsushi; Uchida-Kobayashi, Sawako; Morikawa, Hiroyasu; Enomoto, Masaru; Murakami, Yoshiki; Kawada, Norifumi

    2017-05-03

    We evaluated the transition of dominant resistance-associated substitutions (RASs) in hepatitis C virus during long-term follow-up after the failure of DAAs (direct acting antivirals)-based therapy. RASs in non-structure (NS)3/4A, NS5A, NS5B, and deletions in NS5A from 20 patients who failed simeprevir/pegylated-interferon/ribavirin (SMV/PEG-IFN/RBV) and 25 patients who failed daclatasvir/asunaprevir (DCV/ASV) treatment were examined by direct sequencing. With respect to SMV/PEG-IFN/RBV treatment, RAS was detected at D168 in NS3/4A but not detected in NS5A and NS5B at treatment failure in 16 of 20 patients. During the median follow-up period of 64 weeks, the RAS at D168 became less dominant in 9 of 16 patients. Among 25 DCV/ASV failures, RASs at D168, L31, and Y93 were found in 57.1%, 72.2%, and 76.9%, respectively. NS5A deletions were detected in 3 of 10 patients treated previously with SMV/PEG-IFN/RBV. The number of RASs in the breakthrough patients exceeded that in relapsers (mean 3.9 vs. 2.7, p < 0.05). RAS at D168 in NS3/4A became less dominant in 6 of 15 patients within 80 weeks. Y93H emerged at the time of relapse, then decreased gradually by 99% at 130 weeks post-treatment. Emerged RASs were associated with the clinical course of treatment and could not be detected during longer follow-up.

  4. A translational study of resistance emergence using sequential direct-acting antiviral agents for hepatitis C using ultra-deep sequencing.

    Science.gov (United States)

    Abe, Hiromi; Hayes, C Nelson; Hiraga, Nobuhiko; Imamura, Michio; Tsuge, Masataka; Miki, Daiki; Takahashi, Shoichi; Ochi, Hidenori; Chayama, Kazuaki

    2013-09-01

    Direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) have recently been developed and are ultimately hoped to replace interferon-based therapy. However, DAA monotherapy results in rapid emergence of resistant strains and DAAs must be used in combinations that present a high genetic barrier to resistance, although viral kinetics of multidrug-resistant strains remain poorly characterized. The aim of this study is to track the emergence and fitness of resistance using combinations of telaprevir and NS5A or NS5B inhibitors with genotype 1b clones. HCV-infected chimeric mice were treated with DAAs, and resistance was monitored using direct and ultra-deep sequencing. Combination therapy with telaprevir and BMS-788329 (NS5A inhibitor) reduced serum HCV RNA to undetectable levels. The presence of an NS3-V36A telaprevir resistance mutation resulted in poor response to telaprevir monotherapy but showed significant HCV reduction when telaprevir was combined with BMS-788329. However, a BMS-788329-resistant strain emerged at low frequency. Infection with a BMS-788329-resistant NS5A-L31V mutation rapidly resulted in gain of an additional NS5A-Y93A mutation that conferred telaprevir resistance during combination therapy. Infection with dual NS5AL31V/NS5AY93H mutations resulted in poor response to combination therapy and development of telaprevir resistance. Although HCV RNA became undetectable soon after the beginning of combination therapy with BMS-788329 and BMS-821095 (NS5B inhibitor), rebound with emergence of resistance against all three drugs occurred. Triple resistance also occurred following infection with the NS3V36A/NS5AL31V/NS5AY93H triple mutation. Resistant strains easily develop from cloned virus strains. Sequential use of DAAs should be avoided to prevent emergence of multidrug-resistant strains.

  5. A rare case of perforated "sub-hepatic appendicitis" - a challenging differential diagnosis of acute abdomen based on the combination of appendicitis and maldescent of the caecum.

    Science.gov (United States)

    Chiapponi, Costanza; Jannasch, Olof; Petersen, Manuela; Lessel, Wiebke; Bruns, Christiane; Meyer, Frank

    2017-01-01

    Unusual locations of the appendix vermiformis can result in delay in appropriate diagnosis and treatment of appendicitis. So an inflamed appendix in a sub-hepatic caecum caused by caecal maldescent for example can mimic cholecystitis, the pain being localized in the right upper quadrant. Here, we present a case of perforated sub-hepatic appendicitis with peritonitis, requiring open ileocaecal resection. Review of the existing literature has demonstrated that this pathology is uncommon, yet not so rare as one might presume. In conclusion, surgeons should be aware of this possibility in the diagnostic and therapeutic management of acute abdomen. Copyright © 2016. Published by Elsevier GmbH.

  6. Computed tomography scans of metastatic hepatic tumors

    Energy Technology Data Exchange (ETDEWEB)

    Takemoto, Kazumasa; Fukuda, Haruyuki; Nemoto, Yutaka [Osaka City Univ. (Japan). Faculty of Medicine

    1984-01-01

    Computed tomography scans of 114 metastatic hepatic tumors were reviewed. Central low density was found in 82 cases (71.9%) and seems to be characteristic to metastatic hepatic tumors. Dynamic CT was performed on 34 cases, and 21 (61.8%) of these had ring enhancement at the arterial phase. Most of metastatic hepatic tumors could be differentiated from hepatocellular carcinoma. However, metastatic hepatic tumors from renal cell carcinoma, renal rhabdomyosarcoma, malignant melanoma and leiomyosarcoma could not be differentiated from hepatocellular carcinoma, even with use of dynamic study.

  7. Copeptin in the differential diagnosis of the polydipsia-polyuria syndrome--revisiting the direct and indirect water deprivation tests.

    Science.gov (United States)

    Fenske, Wiebke; Quinkler, Marcus; Lorenz, Daniela; Zopf, Kathrin; Haagen, Ulrike; Papassotiriou, Jana; Pfeiffer, Andreas F H; Fassnacht, Martin; Störk, Stefan; Allolio, Bruno

    2011-05-01

    The water deprivation test (WDT) with direct or indirect measurement of plasma arginine vasopressin (AVP) is the method of choice for the differential diagnosis of the polydipsia-polyuria syndrome. In theory, direct measurement of AVP is highly attractive but is hampered by technical difficulties. The aim of the study was to evaluate the utility of copeptin, a surrogate of AVP secretion, in the diagnostic work-up of the polyuria-polydipsia syndrome and to compare its performance with the current diagnostic standard. In two tertiary referral centers, 20 healthy subjects and 50 patients with polydipsia-polyuria syndrome underwent WDT with measurements of both plasma AVP and copeptin levels. The reference diagnosis was based on clinical information and treatment response. Twenty-two patients (44%) were diagnosed with primary polydipsia, 17 (34%) with partial central diabetes insipidus (DI), nine (18%) with complete central DI, and two (4%) with nephrogenic DI. The indirect WDT led to a correct diagnosis in 35 of 50 patients (70%). The direct WDT with AVP or copeptin measurement correctly diagnosed 23 patients (46%) or 36 patients (72%), respectively. Baseline copeptin values greater than 20 pmol/liter identified patients with nephrogenic DI, and concentrations below 2.6 pmol/liter indicated complete central DI. The ratio between Δ copeptin (0800 to 1600 h) and serum sodium concentration at 1600 h yielded optimal diagnostic accuracy, allowing us to also discern partial central DI from primary polydipsia (sensitivity 86%, and specificity 100%). Copeptin holds promise as a diagnostic tool in the polyuria-polydipsia syndrome, improving significantly the diagnostic accuracy of the direct WDT.

  8. Feature Hepatitis: Hepatitis Can Strike Anyone

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues Feature Hepatitis Hepatitis Can Strike Anyone Past Issues / Spring 2009 Table ... from all walks of life are affected by hepatitis, especially hepatitis C, the most common form of ...

  9. Hepatic Encephalopathy

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    Full Text Available ... Plan Long-Term Considerations Patient Support Finding Support Services Peer Support Groups Financial Assistance Support for My ... is Hepatic Encephalopathy? Why Your Liver is ...

  10. Travelers' Health: Hepatitis C

    Science.gov (United States)

    ... Chapter 3 - Hepatitis B Chapter 3 - Hepatitis E Hepatitis C Deborah Holtzman INFECTIOUS AGENT Hepatitis C virus ( ... mother to child. Map 3-05. Prevalence of hepatitis C virus infection 1 PDF Version (printable) 1 ...

  11. Travelers' Health: Hepatitis A

    Science.gov (United States)

    ... 3 - Helminths, Soil-Transmitted Chapter 3 - Hepatitis B Hepatitis A Noele P. Nelson INFECTIOUS AGENT Hepatitis A ... hepatitis/HAV Table 3-02. Vaccines to prevent hepatitis A VACCINE TRADE NAME (MANUFACTURER) AGE (Y) DOSE ...

  12. Hepatitis (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Hepatitis KidsHealth / For Parents / Hepatitis Print en español Hepatitis What Is Hepatitis? Hepatitis is an inflammation of the liver. The ...

  13. Travelers' Health: Hepatitis B

    Science.gov (United States)

    ... Chapter 3 - Hepatitis A Chapter 3 - Hepatitis C Hepatitis B Francisco Averhoff INFECTIOUS AGENT Hepatitis B virus ( ... progression of disease. Map 3-04. Prevalence of hepatitis B virus infection 1 PDF Version (printable) 1 ...

  14. Hepatitis C: Clinical Trials

    Science.gov (United States)

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

  15. Hepatitis C: Mental Health

    Science.gov (United States)

    ... the Public Home Hepatitis A Hepatitis B Hepatitis C Hepatitis C Home Getting Tested Just Diagnosed Treatment Choice Program ... Pain Mental Health Sex and Sexuality (for Hepatitis C) Success Stories FAQs For Health Care Providers Provider ...

  16. A novel technique for optimal integration of active steering and differential braking with estimation to improve vehicle directional stability.

    Science.gov (United States)

    Mirzaeinejad, Hossein; Mirzaei, Mehdi; Rafatnia, Sadra

    2018-06-11

    This study deals with the enhancement of directional stability of vehicle which turns with high speeds on various road conditions using integrated active steering and differential braking systems. In this respect, the minimum usage of intentional asymmetric braking force to compensate the drawbacks of active steering control with small reduction of vehicle longitudinal speed is desired. To this aim, a new optimal multivariable controller is analytically developed for integrated steering and braking systems based on the prediction of vehicle nonlinear responses. A fuzzy programming extracted from the nonlinear phase plane analysis is also used for managing the two control inputs in various driving conditions. With the proposed fuzzy programming, the weight factors of the control inputs are automatically tuned and softly changed. In order to simulate a real-world control system, some required information about the system states and parameters which cannot be directly measured, are estimated using the Unscented Kalman Filter (UKF). Finally, simulations studies are carried out using a validated vehicle model to show the effectiveness of the proposed integrated control system in the presence of model uncertainties and estimation errors. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

  17. Neuroplastic effects of transcranial direct current stimulation on painful symptoms reduction in chronic Hepatitis C: a phase II randomized, double blind, sham controlled trial

    Directory of Open Access Journals (Sweden)

    Aline Patricia Brietzke

    2016-01-01

    Full Text Available Introduction: Pegylated Interferon Alpha (Peg-IFN in combination with other drugs is the standard treatment for chronic hepatitis C infection (HCV and is related to severe painful symptoms. The aim of this study was access the efficacy of transcranial direct current stimulation (tDCS in controlling the painful symptoms related to Peg-IFN side effects. Material and Methods: In this phase II double-blind trial, twenty eight (n=28 HCV subjects were randomized to receive either five consecutive days of active tDCS (n=14 or sham (n=14 during five consecutive days with anodal stimulation over the primary motor cortex region using 2 mA for 20 minutes. The primary outcomes were visual analogue scale (VAS pain and brain-derived neurotrophic factor (BDNF serum levels. Secondary outcomes were the pressure-pain threshold (PPT, the Brazilian Profile of Chronic Pain: Screen (B-PCP:S and drug analgesics use. Results: tDCS reduced the VAS scores (P<0.003, with a mean pain drop of 56% (p<0.001. Furthermore, tDCS was able to enhance BDNF levels (p<0.01. The mean increase was 37.48% in the active group. Finally, tDCS raised PPT (p<0.001 and reduced the B-PCP:S scores and analgesic use (p<0.05. Conclusions: Five sessions of tDCS were effective in reducing the painful symptoms in HCV patients undergoing Peg-IFN treatment. These findings support the efficacy of tDCS as a promising therapeutic tool to improve the tolerance of the side effects related to the use of Peg-IFN. Future larger studies (phase III and IV trials are needed to confirm the clinical use of the therapeutic effects of tDCS in such condition. Trial registration: Brazilian Human Health Regulator for Research with the approval number CAAE 07802012.0.0000.5327

  18. Effectiveness of direct-acting antiviral therapy for hepatitis C in difficult-to-treat patients in a safety-net health system: a retrospective cohort study.

    Science.gov (United States)

    Yek, Christina; de la Flor, Carolina; Marshall, John; Zoellner, Cindy; Thompson, Grace; Quirk, Lisa; Mayorga, Christian; Turner, Barbara J; Singal, Amit G; Jain, Mamta K

    2017-11-20

    Direct-acting antivirals (DAAs) have revolutionized chronic hepatitis C (HCV) treatment, but real-world effectiveness among vulnerable populations, including uninsured patients, is lacking. This study was conducted to characterize the effectiveness of DAAs in a socioeconomically disadvantaged and underinsured patient cohort. This retrospective observational study included all patients undergoing HCV treatment with DAA-based therapy between April 2014 and June 2016 at a large urban safety-net health system (Parkland Health and Hospital System, Dallas, TX, USA). The primary outcome was sustained virologic response (SVR), with secondary outcomes including treatment discontinuation, treatment relapse, and loss to follow-up. DAA-based therapy was initiated in 512 patients. The cohort was socioeconomically disadvantaged (56% uninsured and 13% Medicaid), with high historic rates of alcohol (41%) and substance (50%) use, and mental health disorders (38%). SVR was achieved in 90% of patients (n = 459); 26 patients (5%) were lost to follow-up. SVR was significantly lower in patients with decompensated cirrhosis (82% SVR; OR 0.37, 95% CI 0.16-0.85) but did not differ by insurance status (P = 0.98) or alcohol/substance use (P = 0.34). Reasons for treatment failure included loss to follow-up (n = 26, 5%), viral relapse (n = 16, 3%), non-treatment-related death (n = 7, 1%), and treatment discontinuation (n = 4, 1%). Of patients with viral relapse, 6 reported non-compliance and have not been retreated, 5 have been retreated and achieved SVR, 4 have undergone resistance testing but not yet initiated retreatment, and 1 was lost to follow-up. Effective outcomes with DAA-based therapy can be achieved in difficult-to-treat underinsured populations followed in resource-constrained safety-net health systems.

  19. Moderate Sustained Virologic Response Rates With 6-Week Combination Directly Acting Anti-Hepatitis C Virus Therapy in Patients With Advanced Liver Disease.

    Science.gov (United States)

    Kattakuzhy, Sarah; Wilson, Eleanor; Sidharthan, Sreetha; Sims, Zayani; McLaughlin, Mary; Price, Angie; Silk, Rachel; Gross, Chloe; Akoth, Elizabeth; McManus, Maryellen; Emmanuel, Benjamin; Shrivastava, Shikha; Tang, Lydia; Nelson, Amy; Teferi, Gebeyehu; Chavez, Jose; Lam, Brian; Mo, Hongmei; Osinusi, Anuoluwapo; Polis, Michael A; Masur, Henry; Kohli, Anita; Kottilil, Shyamasundaran

    2016-02-15

    Treatment of genotype 1 hepatitis C virus (HCV) infection with combination directly acting antivirals (DAA) for 8-24 weeks is associated with high rates of sustained virologic response (SVR). We previously demonstrated that adding a third DAA to ledipasvir and sofosbuvir (LDV/SOF) can result in high SVR rates in patients without cirrhosis. In this study, we investigated whether a similar regimen would yield equivalent rates of cure in patients with advanced liver fibrosis. Fifty patients were enrolled at the Clinical Research Center of the National Institutes of Health and associated healthcare centers. Enrollment and follow-up data from April 2014 to June 2015 are reported here. Eligible participants were aged ≥18 years, had chronic HCV genotype 1 infection (serum HCV RNA ≥2000 IU/mL), and stage 3-4 liver fibrosis. HCV RNA was measured using a reverse-transcription polymerase chain reaction assay. Of patients treated with LDV, SOF, and the NS3/4A protease inhibitor GS-9451 for 6 weeks, 76% (38 of 50; 95% confidence interval, 60%-85%) had SVR achieved 12 weeks after the end of treatment. There was no statistically significant difference in treatment efficacy between treatment-naive patients (72%, 18 of 25) and those with treatment experience (80%; 20 of 25) (P = .51). Overall, 11 patients (22%) experienced virologic relapse, and 1 (2%) was lost to follow-up at 4 weeks after treatment. No serious adverse events, discontinuations, or deaths were associated with this regimen. Adding a third DAA to LDV/SOF may result in a moderate SVR rate, lower than that observed in patients without cirrhosis. Significant liver fibrosis remains an impediment to achieving SVR with short-duration DAA therapy. CT01805882. Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  20. Pros and Cons: Usage of organs from donors infected with hepatitis C virus - Revision in the direct-acting antiviral era.

    Science.gov (United States)

    Coilly, Audrey; Samuel, Didier

    2016-01-01

    Should organs from hepatitis C antibody positive donors (HCVD+) be used for transplantation? Organ shortage forces transplant teams to use donors with extended criteria. The decision to transplant a HCVD+ graft is a balance between the risk of transmission of a virus that could lead to end-stage liver diseases and the benefit of access to transplantation, specifically in patients with life-threatening disease. The other issue is the impact of HCV-related liver fibrosis in the donor graft on the long-term outcome in the recipient. Thus, the use of HCVD+ demonstrated a shorter meantime on the waiting list in kidney transplantation. When a HCVD+ graft is transplanted, the risk of HCV transmission depends on; 1) the quality of screening of the donor; 2) the presence of viral replication in the donor at the time of transplantation and the ability to detect it; and 3) the HCV status of the recipient but also the type of transplanted organ. In liver transplantation, the use of HCVD+ graft is usually restricted to recipients with a chronic HCV infection. Several reports showed some competition between HCV donor and recipient strain without deleterious impact on graft and patient survival. Controversies are still pending regarding the quality of the graft and the progression of fibrosis. The recent approval of direct-acting antiviral agents (DAA) dramatically changes the landscape of HCV infection treatment. After transplantation, combinations of DAA show high efficacy and good safety profile. In the near future, extensive use of DAA should reduce the number of HCVD+ with a positive HCV RNA, limiting the risk of transmission but also the number of patients on waiting lists for a disease related to HCV. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  1. Naturally Occurring Resistance-Associated Variants to Hepatitis C Virus Direct-Acting Antiviral Agents in Treatment-Naive HCV Genotype 6a-Infected Patients

    Directory of Open Access Journals (Sweden)

    Zhanyi Li

    2017-01-01

    Full Text Available Background and Objective. The direct-acting antiviral agents (DAAs antiviral therapy has drastically improved the prognosis of hepatitis C virus (HCV patients. However, the viral drug resistance-associated variants (RAVs can limit the efficacy of DAAs. For the HCV-6a is not the predominant prevalent genotype; the data on the prevalence of naturally occurring RAVs in it is scarce. Our study aims to assess the prevalence of RAVs in treatment-naive HCV-6a patients. Methods. Nested PCR assays were performed on 95 HCV-6a patients to amplify HCV viral regions of NS3, NS5A, and NS5B. Results. In NS3/4A region, we detected Q80K in 95.5% isolates (84/88 and D168E in 2.3% isolates (2/88. In NS5A region, we detected Q30R in 93.2% isolates (82/88, L31M in 4.6% isolates (4/88, and H58P in 6.8% isolates (6/88. In NS5B region, we detected A15G in 2.3% isolates (2/88, S96T in 1.1% isolates (1/88, and S282T in 20.7% isolates (17/88 and we detected I482L in 100% isolates (4/4, V494A in 50% isolates (2/4, and V499A in 100% isolates (4/4. Conclusions. RAVs to DAAs preexist in treatment-naive HCV-6a patients. Further studies should address the issue of the impact of RAVs in response to DAA therapies for HCV-6a patients.

  2. Micro-costing analysis of guideline-based treatment by direct-acting agents: the real-life case of hepatitis C management in Brazil.

    Science.gov (United States)

    Perazzo, Hugo; Jorge, Marcelino Jose; Silva, Julio Castro; Avellar, Alexandre Monken; Silva, Patrícia Santos; Romero, Carmen; Veloso, Valdilea Gonçalves; Mujica-Mota, Ruben; Anderson, Rob; Hyde, Chris; Castro, Rodolfo

    2017-11-23

    Eradication of hepatitis C virus (HCV) using direct-acting agents (DAA) has been associated with a financial burden to health authorities worldwide. We aimed to evaluate the guideline-based treatment costs by DAAs from the perspective of the Brazilian Ministry of Health (BMoH). The activity based costing method was used to estimate the cost for monitoring/treatment of genotype-1 (GT1) HCV patients by the following strategies: peg-interferon (PEG-IFN)/ribavirin (RBV) for 48 weeks, PEG-IFN/RBV plus boceprevir (BOC) or telaprevir (TEL) for 48 weeks, and sofosbuvir (SOF) plus daclastavir (DCV) or simeprevir (SIM) for 12 weeks. Costs were reported in United States Dollars without (US$) and with adjustment for purchasing power parity (PPP$). Drug costs were collected at the National Database of Health Prices and an overview of the literature was performed to assess effectiveness of SOF/DCV and SOF/SIM regimens in real-world cohorts. Treatment costs of GT1-HCV patients were PPP$ 43,176.28 (US$ 24,020.16) for PEG-IFN/RBV, PPP$ 71,196.03 (US$ 39,578.23) for PEG-IFN/RBV/BOC and PPP$ 86,250.33 (US$ 47,946.92) for PEG-IFN/RBV/TEL. Treatment by all-oral interferon-free regimens were the less expensive approach: PPP$ 19,761.72 (US$ 10,985.90) for SOF/DCV and PPP$ 21,590.91 (US$ 12,002.75) for SOF/SIM. The overview reported HCV eradication in up to 98% for SOF/DCV and 96% for SOF/SIM. Strategies with all oral interferon-free might lead to lower costs for management of GT1-HCV patients compared to IFN-based regimens in Brazil. This occurred mainly because of high discounts over international DAA prices due to negotiation between BMoH and pharmaceutical industries.

  3. Modelling how reversal of immune exhaustion elicits cure of chronic hepatitis C after the end of treatment with direct-acting antiviral agents.

    Science.gov (United States)

    Baral, Subhasish; Roy, Rahul; Dixit, Narendra M

    2018-05-09

    A fraction of chronic hepatitis C patients treated with direct-acting antivirals (DAAs) achieved sustained virological responses (SVR), or cure, despite having detectable viremia at the end of treatment (EOT). This observation, termed EOT + /SVR, remains puzzling and precludes rational optimization of treatment durations. One hypothesis to explain EOT + /SVR, the immunologic hypothesis, argues that the viral decline induced by DAAs during treatment reverses the exhaustion of cytotoxic T lymphocytes (CTLs), which then clear the infection after treatment. Whether the hypothesis is consistent with data of viral load changes in patients who experienced EOT + /SVR is unknown. Here, we constructed a mathematical model of viral kinetics incorporating the immunologic hypothesis and compared its predictions with patient data. We found the predictions to be in quantitative agreement with patient data. Using the model, we unraveled an underlying bistability that gives rise to EOT + /SVR and presents a new avenue to optimize treatment durations. Infected cells trigger both activation and exhaustion of CTLs. CTLs in turn kill infected cells. Due to these competing interactions, two stable steady states, chronic infection and viral clearance, emerge, separated by an unstable steady state with intermediate viremia. When treatment during chronic infection drives viremia sufficiently below the unstable state, spontaneous viral clearance results post-treatment, marking EOT + /SVR. The duration to achieve this desired reduction in viremia defines the minimum treatment duration required for ensuring SVR, which our model can quantify. Estimating parameters defining the CTL response of individuals to HCV infection would enable the application of our model to personalize treatment durations. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  4. Improvement of liver stiffness in patients with hepatitis C virus infection who received direct-acting antiviral therapy and achieved sustained virological response.

    Science.gov (United States)

    Tada, Toshifumi; Kumada, Takashi; Toyoda, Hidenori; Mizuno, Kazuyuki; Sone, Yasuhiro; Kataoka, Saki; Hashinokuchi, Shinichi

    2017-12-01

    There is insufficient research on whether direct-acting antiviral (DAA) therapy can improve liver fibrosis in patients with chronic hepatitis C virus (HCV). We evaluated sequential changes in liver stiffness using shear wave elastography in patients with HCV who received DAA therapy. A total of 210 patients with HCV who received daclatasvir and asunaprevir therapy and achieved sustained virological response (SVR) were analyzed. Liver stiffness, as evaluated by shear wave elastography, and laboratory data were assessed before treatment (baseline), at end of treatment (EOT), and at 24 weeks after EOT (SVR24). Alanine aminotransferase levels (ALT) decreased over time, and there were significant differences between baseline and EOT and between EOT and SVR24. Although platelet counts did not significantly differ between baseline and EOT, they increased significantly from EOT to SVR24. The median (interquartile range) liver stiffness values at baseline, EOT, and SVR24 were 10.2 (7.7-14.7), 8.8 (7.1-12.1), and 7.6 (6.3-10.3) kPa, respectively (P liver) and Fibrosis-4 index > 2.0 (n = 75), the liver stiffness values at baseline, EOT, and SVR24 were 9.6 (7.7-15.2), 9.2 (7.3-12.1), and 7.7 (6.3-10.1) kPa, respectively (P liver stiffness starts during the administration of DAAs in patients who achieve SVR, and this effect is particularly pronounced in patients with progressive liver fibrosis. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  5. Alcoholic Hepatitis

    Science.gov (United States)

    ... yellow color. Confusion, drowsiness and slurred speech (hepatic encephalopathy). A damaged liver has trouble removing toxins from your body. The ... of toxins can damage your brain. Severe hepatic encephalopathy can result in ... of the liver frequently leads to liver failure. Kidney failure. A ...

  6. Lycopene and Apo-10′-lycopenoic Acid Have Differential Mechanisms of Protection against Hepatic Steatosis in β-Carotene-9′,10′-oxygenase Knockout Male Mice123

    Science.gov (United States)

    Ip, Blanche C; Liu, Chun; Lichtenstein, Alice H; von Lintig, Johannes; Wang, Xiang-Dong

    2015-01-01

    Background: Nonalcoholic fatty liver disease is positively associated with obesity and cardiovascular disease risk. Apo-10′-lycopenoic acid (APO10LA), a potential oxidation product of apo-10′-lycopenal that is generated endogenously by β-carotene-9′,10′-oxygenase (BCO2) cleavage of lycopene, inhibited hepatic steatosis in BCO2-expressing mice. Objective: The present study evaluated lycopene and APO10LA effects on hepatic steatosis in mice without BCO2 expression. Methods: Male and female BCO2-knockout (BCO2-KO) mice were fed a high saturated fat diet (HSFD) with or without APO10LA (10 mg/kg diet) or lycopene (100 mg/kg diet) for 12 wk. Results: Lycopene or APO10LA supplementation reduced hepatic steatosis incidence (78% and 72%, respectively) and severity in BCO2-KO male mice. Female mice did not develop steatosis, had greater hepatic total cholesterol (3.06 vs. 2.31 mg/g tissue) and cholesteryl ester (1.58 vs. 0.86 mg/g tissue), but had lower plasma triglyceride (TG) (229 vs. 282 mg/dL) and cholesterol (97.1 vs. 119 mg/dL) than male mice. APO10LA-mitigated steatosis in males was associated with reduced hepatic total cholesterol (18%) and activated sirtuin 1 signaling, which resulted in reduced fatty acids (FAs) and TG synthesis markers [stearoyl-coenzyme A (CoA) desaturase protein, 71%; acetyl-CoA carboxylase phosphorylation, 79%; AMP-activated protein kinase phosphorylation, 67%], and elevated cholesterol efflux genes (cytochrome P450 family 7A1, 65%; ATP-binding cassette transporter G5/8, 11%). These APO10LA-mediated effects were not mimicked by lycopene supplementation. Intriguingly, steatosis inhibition by lycopene induced peroxisome proliferator–activated receptor (PPAR)α- and PPARγ-related genes in mesenteric adipose tissue (MAT) that increases mitochondrial uncoupling [cell death–inducing DNA fragmentation factor, α subunit-like effector a, 55%; PR domain-containing 16, 47%; uncoupling protein 3 (Ucp3), 55%], FA β-oxidation (PPARα, 53

  7. Parvovirus B19 associated acute cholestatic hepatitis

    Directory of Open Access Journals (Sweden)

    S. Perrini

    2014-12-01

    Full Text Available There are few reports in the literature of hepatitis as a manifestation of Parvovirus B19 infection. We describe a case of Parvovirus B19 associated acute cholestatic hepatitis diagnosed based on a positive serologic test (IgM and molecular detection of parvovirus B19 DNA in peripheral blood. Parvovirus B19 infection should be considered in the differential diagnosis of patient presenting with acute hepatitis of unknown etiology.

  8. Neonatal Persistent Exposure to 6-Propyl-2-thiouracil, a Thyroid-Disrupting Chemical, Differentially Modulates Expression of Hepatic Catalase and C/EBP-β in Adult Rats.

    Science.gov (United States)

    Bunker, Suresh Kumar; Dandapat, Jagneshwar; Sahoo, Sunil Kumar; Roy, Anita; Chainy, Gagan B N

    2016-02-01

    Persistent exposure of rats to 6-propyl-2-thiouracil (PTU) from birth resulted in decreases in plasma thyroid hormone (TH) levels and hepatic expression of catalase and CCAAT enhancer binding protein β (C/EBP-β). Catalase promoter region (-185 to +52) that contains binding sites for C/EBP-β showed an augmentation in the methylation level along with a change in methylation pattern of CpG islands in response to PTU treatment. PTU withdrawal on 30 days of birth restored TH levels and C/EBP-β to control rats in adulthood. Although catalase expression was restored to some extent in adult rats in response to PTU withdrawal, a permanent change in its promoter CpG methylation pattern was recorded. The results suggest that downregulation of adult hepatic catalase gene in response to persistent neonatal PTU exposure may not solely be attributed to thyroid-disrupting properties of PTU. It is possible that besides thyroid-disrupting behavior, PTU may impair expression of hepatic catalase by altering methylation pattern of its promoter. © 2015 Wiley Periodicals, Inc.

  9. Liver scintigraphy of fulminant hepatitis

    International Nuclear Information System (INIS)

    Tamaki, Nagara; Ishihara, Takashi; Mori, Toru

    1980-01-01

    The liver scintigraphies of five patients with fulminant hepatitis were examined. Scintiphotos using sup(99m)Tc-phytate were taken within two weeks after the onset. Scintiphotos of 12 normal subjects, 11 cases with acute hepatitis, 17 cases with liver cirrhosis were served as control. Their scintiphotos showed reduction of the size, well-maintained uptake, mostly homogenous RI distribution, and no left lobe enlargement, which could differentiate them from the chronic liver dysfunction. In one of the cases chronological changes in liver scintigraphy were observed. The size of the liver was reduced progressively until the 16th day and re-enlarged at the 30th day and thereafter. Three indices [S/W, (R + L)/W, and L/R] were calculated. S: area of liver, R or L: longitudinal length of the right or left lobe, W: body width. Relative size of the liver expressed by S/W or (R + L)/W showed significant reduction in fulminant hepatitis compared with acute hepatitis. However, they were not different significantly from those of normal subjects. Except for liver cirrhosis, L/R (left lobe swelling index) did not show significant differences among fulminant hepatitis, normal subjects, and acute hepatitis. These indices were also useful in follow-up study of the liver scintigraphy. The liver scintigraphy in the early phase of fulminant hepatitis seems to reflect the degree of massive hepatic necrosis. It is also useful to differentiate chronic hepatic failure. Apparant reduction in scintigraphical liver size seems to suggest poor prognosis, however, it should also kept in mind that the size of the liver in this condition might change quite rapidly and greatly. (author)

  10. Differential behavioral and physiological effects of anodal transcranial direct current stimulation in healthy adults of younger and older age

    Science.gov (United States)

    Heise, Kirstin-Friederike; Niehoff, Martina; Feldheim, J.-F.; Liuzzi, Gianpiero; Gerloff, Christian; Hummel, Friedhelm C.

    2014-01-01

    Changes in γ-aminobutyric acid (GABA) mediated synaptic transmission have been associated with age-related motor and cognitive functional decline. Since anodal transcranial direct current stimulation (atDCS) has been suggested to target cortical GABAergic inhibitory interneurons, its potential for the treatment of deficient inhibitory activity and functional decline is being increasingly discussed. Therefore, after-effects of a single session of atDCS on resting-state and event-related short-interval intracortical inhibition (SICI) as evaluated with double-pulse TMS and dexterous manual performance were examined using a sham-controlled cross-over design in a sample of older and younger participants. The atDCS effect on resting-state inhibition differed in direction, magnitude, and timing, i.e., late relative release of inhibition in the younger and early relative increase in inhibition in the older. More pronounced release of event-related inhibition after atDCS was exclusively seen in the older. Event-related modulation of inhibition prior to stimulation predicted the magnitude of atDCS-induced effects on resting-state inhibition. Specifically, older participants with high modulatory capacity showed a disinhibitory effect comparable to the younger. Beneficial effects on behavior were mainly seen in the older and in tasks requiring higher dexterity, no clear association with physiological changes was found. Differential effects of atDCS on SICI, discussed to reflect GABAergic inhibition at the level of the primary motor cortex, might be distinct in older and younger participants depending on the functional integrity of the underlying neural network. Older participants with preserved modulatory capacity, i.e., a physiologically “young” motor network, were more likely to show a disinhibitory effect of atDCS. These results favor individually tailored application of tDCS with respect to specific target groups. PMID:25071555

  11. Differential effects of bihemispheric and unihemispheric transcranial direct current stimulation in young and elderly adults in verbal learning.

    Science.gov (United States)

    Fiori, Valentina; Nitsche, Michael; Iasevoli, Luigi; Cucuzza, Gabriella; Caltagirone, Carlo; Marangolo, Paola

    2017-03-15

    For the past few years, the potential of transcranial direct current stimulation (tDCS) for the treatment of several pathologies has been investigated. In the language domain, several studies, in healthy and brain-damaged populations, have already shown that tDCS is effective in enhancing naming, repetition and semantic word generation. In those studies, different tDCS electrode configurations have been tested, however, a direct comparison between different montages in verbal learning has never been conducted. In this study, we aimed to explore the impact of bihemispheric and unihemispheric tDCS on verbal learning task performance in two groups (young vs. elderly). Fifteen healthy volunteers participated per group. Each participant received three stimulation conditions: unihemispheric anodal tDCS over the left temporal area, bihemispheric tDCS over the left (anodal) and right (cathodal) temporal areas and a sham condition. During active stimulation, tDCS (20min, 2mA) was applied while each participant learned twenty pseudowords (arbitrarily assigned to corresponding pictures). No significant differences were found between the three conditions for the young group with regard to accuracy and vocal reaction times. In contrast, in the elderly group, real stimulation improved performance compared to sham but bihemispheric tDCS was more efficient than unilateral stimulation. These results suggest that bihemispheric stimulation is more effective in improving language learning but this effect is age-dependent. The hypothesis is advanced that cortical changes in the course of aging might differentially impact on tDCS efficacy on behavioral performance. These data may also have implications for treatment of stroke patients with language impairment. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Airborne Measurements of CO2 Column Absorption and Range Using a Pulsed Direct-Detection Integrated Path Differential Absorption Lidar

    Science.gov (United States)

    Abshire, James B.; Riris, Haris; Weaver, Clark J.; Mao, Jianping; Allan, Graham R.; Hasselbrack, William E.; Browell, Edward V.

    2013-01-01

    We report on airborne CO2 column absorption measurements made in 2009 with a pulsed direct-detection lidar operating at 1572.33 nm and utilizing the integrated path differential absorption technique. We demonstrated these at different altitudes from an aircraft in July and August in flights over four locations in the central and eastern United States. The results show clear CO2 line shape and absorption signals, which follow the expected changes with aircraft altitude from 3 to 13 km. The lidar measurement statistics were also calculated for each flight as a function of altitude. The optical depth varied nearly linearly with altitude, consistent with calculations based on atmospheric models. The scatter in the optical depth measurements varied with aircraft altitude as expected, and the median measurement precisions for the column varied from 0.9 to 1.2 ppm. The altitude range with the lowest scatter was 810 km, and the majority of measurements for the column within it had precisions between 0.2 and 0.9 ppm.

  13. Direct differentiation of the quasi-incompressible fluid formulation of fluid-structure interaction using the PFEM

    Science.gov (United States)

    Zhu, Minjie; Scott, Michael H.

    2017-07-01

    Accurate and efficient response sensitivities for fluid-structure interaction (FSI) simulations are important for assessing the uncertain response of coastal and off-shore structures to hydrodynamic loading. To compute gradients efficiently via the direct differentiation method (DDM) for the fully incompressible fluid formulation, approximations of the sensitivity equations are necessary, leading to inaccuracies of the computed gradients when the geometry of the fluid mesh changes rapidly between successive time steps or the fluid viscosity is nonzero. To maintain accuracy of the sensitivity computations, a quasi-incompressible fluid is assumed for the response analysis of FSI using the particle finite element method and DDM is applied to this formulation, resulting in linearized equations for the response sensitivity that are consistent with those used to compute the response. Both the response and the response sensitivity can be solved using the same unified fractional step method. FSI simulations show that although the response using the quasi-incompressible and incompressible fluid formulations is similar, only the quasi-incompressible approach gives accurate response sensitivity for viscous, turbulent flows regardless of time step size.

  14. Myostatin is a direct regulator of osteoclast differentiation and its inhibition reduces inflammatory joint destruction in mice.

    Science.gov (United States)

    Dankbar, Berno; Fennen, Michelle; Brunert, Daniela; Hayer, Silvia; Frank, Svetlana; Wehmeyer, Corinna; Beckmann, Denise; Paruzel, Peter; Bertrand, Jessica; Redlich, Kurt; Koers-Wunrau, Christina; Stratis, Athanasios; Korb-Pap, Adelheid; Pap, Thomas

    2015-09-01

    Myostatin (also known as growth and differentiation factor 8) is a secreted member of the transforming growth factor-β (TGF-β) family that is mainly expressed in skeletal muscle, which is also its primary target tissue. Deletion of the myostatin gene (Mstn) in mice leads to muscle hypertrophy, and animal studies support the concept that myostatin is a negative regulator of muscle growth and regeneration. However, myostatin deficiency also increases bone formation, mainly through loading-associated effects on bone. Here we report a previously unknown direct role for myostatin in osteoclastogenesis and in the progressive loss of articular bone in rheumatoid arthritis (RA). We demonstrate that myostatin is highly expressed in the synovial tissues of RA subjects and of human tumor necrosis factor (TNF)-α transgenic (hTNFtg) mice, a model for human RA. Myostatin strongly accelerates receptor activator of nuclear factor κB ligand (RANKL)-mediated osteoclast formation in vitro through transcription factor SMAD2-dependent regulation of nuclear factor of activated T-cells (NFATC1). Myostatin deficiency or antibody-mediated inhibition leads to an amelioration of arthritis severity in hTNFtg mice, chiefly reflected by less bone destruction. Consistent with these effects in hTNFtg mice, the lack of myostatin leads to increased grip strength and less bone erosion in the K/BxN serum-induced arthritis model in mice. The results strongly suggest that myostatin is a potent therapeutic target for interfering with osteoclast formation and joint destruction in RA.

  15. Differentiation and sarcomere formation in skeletal myocytes directly prepared from human induced pluripotent stem cells using a sphere-based culture.

    Science.gov (United States)

    Jiwlawat, Saowanee; Lynch, Eileen; Glaser, Jennifer; Smit-Oistad, Ivy; Jeffrey, Jeremy; Van Dyke, Jonathan M; Suzuki, Masatoshi

    Human induced-pluripotent stem cells (iPSCs) are a promising resource for propagation of myogenic progenitors. Our group recently reported a unique protocol for the derivation of myogenic progenitors directly (without genetic modification) from human pluripotent cells using free-floating spherical culture. Here we expand our previous efforts and attempt to determine how differentiation duration, culture surface coatings, and nutrient supplements in the medium influence progenitor differentiation and formation of skeletal myotubes containing sarcomeric structures. A long differentiation period (over 6 weeks) promoted the differentiation of iPSC-derived myogenic progenitors and subsequent myotube formation. These iPSC-derived myotubes contained representative sarcomeric structures, consisting of organized myosin and actin filaments, and could spontaneously contract. We also found that a bioengineering approach using three-dimensional (3D) artificial muscle constructs could facilitate the formation of elongated myotubes. Lastly, we determined how culture surface coating matrices and different supplements would influence terminal differentiation. While both Matrigel and laminin coatings showed comparable effects on muscle differentiation, B27 serum-free supplement in the differentiation medium significantly enhanced myogenesis compared to horse serum. Our findings support the possibility to create an in vitro model of contractile sarcomeric myofibrils for disease modeling and drug screening to study neuromuscular diseases. Copyright © 2017 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  16. Hepatic angiography: Portal hypertension

    International Nuclear Information System (INIS)

    Oliver, T.W. Jr.; Sones, P.J. Jr.

    1985-01-01

    Portal hypertension is usually a manifestation of underlying hepatic parenchymal disease, although it may be secondary to portal or hepatic venous thrombosis and rarely to hyperdynamic portal states. Portal hypertension may present as encephalopathy, ascites, jaundice, hepatic failure, or catastrophic upper gastrointestinal hemorrhage. Radiologic investigation should include indirect or direct measurements of portal pressure, assessment of portal venous perfusion, visualization of collaterals, and demonstration of arterial and venous anatomy for potential shunt procedure. Following survival of initial variceal bleeding, the most effective procedure to prevent recurrent hemorrhage is a shunt to decompress the varices. The decision whether to intervene medically or surgically during the acute hemorrhagic episode as well as the type of shunt used to prevent future hemorrhage is the subject of continuing controversy

  17. Intrauterine growth restriction and differential patterns of hepatic growth and expression of IGF1, PCK2, and HSDL1 mRNA in the sheep fetus in late gestation.

    Science.gov (United States)

    Gentili, Sheridan; Morrison, Janna L; McMillen, I Caroline

    2009-06-01

    Fetal adaptations to periods of substrate deprivation can result in the programming of glucose intolerance, insulin resistance, and metabolic dysfunction in later life. Placental insufficiency can be associated with either sparing or sacrifice of fetal liver growth, and these different responses may have different metabolic consequences. It is unclear what intrahepatic mechanisms determine the differential responses of the fetal liver to substrate restriction. We investigated the effects of placental restriction (PR) on liver growth and the hepatic expression of SLC2A1, IGF1, IGF2, IGF1R, IGF2R, PPARGC1A, PPARA, PRKAA1, PRKAA2, PCK2, and HSDL1 mRNA in fetal sheep at 140-145 days of gestation. A mean gestational arterial partial pressure of oxygen less than 17 mmHg was defined as hypoxic, and a relative liver of weight more than 2 SD below the mean liver weight of controls was defined as reduced liver growth. Fetuses therefore were defined as control-normoxic (C-N; n = 9), PR-normoxic (PR-N; n = 7), PR-hypoxic (PR-H; n = 8), or PR-hypoxic reduced liver growth (PR-H RLG; n = 4). Hepatic SLC2A1 mRNA expression was highest (P fetal substrate restriction may exist that protect the liver from decreased growth and, potentially, from a decreased responsiveness to the actions of insulin in postnatal life.

  18. SOX9 governs differentiation stage-specific gene expression in growth plate chondrocytes via direct concomitant transactivation and repression.

    Directory of Open Access Journals (Sweden)

    Victor Y L Leung

    2011-11-01

    Full Text Available Cartilage and endochondral bone development require SOX9 activity to regulate chondrogenesis, chondrocyte proliferation, and transition to a non-mitotic hypertrophic state. The restricted and reciprocal expression of the collagen X gene, Col10a1, in hypertrophic chondrocytes and Sox9 in immature chondrocytes epitomise the precise spatiotemporal control of gene expression as chondrocytes progress through phases of differentiation, but how this is achieved is not clear. Here, we have identified a regulatory element upstream of Col10a1 that enhances its expression in hypertrophic chondrocytes in vivo. In immature chondrocytes, where Col10a1 is not expressed, SOX9 interacts with a conserved sequence within this element that is analogous to that within the intronic enhancer of the collagen II gene Col2a1, the known transactivation target of SOX9. By analysing a series of Col10a1 reporter genes in transgenic mice, we show that the SOX9 binding consensus in this element is required to repress expression of the transgene in non-hypertrophic chondrocytes. Forced ectopic Sox9 expression in hypertrophic chondrocytes in vitro and in mice resulted in down-regulation of Col10a1. Mutation of a binding consensus motif for GLI transcription factors, which are the effectors of Indian hedgehog signaling, close to the SOX9 site in the Col10a1 regulatory element, also derepressed transgene expression in non-hypertrophic chondrocytes. GLI2 and GLI3 bound to the Col10a1 regulatory element but not to the enhancer of Col2a1. In addition to Col10a1, paired SOX9-GLI binding motifs are present in the conserved non-coding regions of several genes that are preferentially expressed in hypertrophic chondrocytes and the occurrence of pairing is unlikely to be by chance. We propose a regulatory paradigm whereby direct concomitant positive and negative transcriptional control by SOX9 ensures differentiation phase-specific gene expression in chondrocytes. Discrimination between

  19. Karyotype differentiation in Chromaphyosemion killifishes (Cyprinodontiformes, Nothobranchiidae)II: Cytogenetic and mitochondrial DNA analyses demostrate karyotype differentiation and its evolutionary direction in C. riggenbachi

    Czech Academy of Sciences Publication Activity Database

    Völker, M.; Sonnenberg, R.; Ráb, Petr; Kullmann, H.

    2006-01-01

    Roč. 115, 1 (2006), s. 70-83 ISSN 1424-8581 Grant - others:DFG Ku-1469/2-1; DFG Mi-649/2-1; DAAD D/03/44465 Institutional research plan: CEZ:AV0Z50450515 Keywords : karyotype differentiation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.993, year: 2006

  20. miR-122 promotes hepatic antioxidant defense of genetically improved farmed tilapia (GIFT, Oreochromis niloticus) exposed to cadmium by directly targeting a metallothionein gene

    International Nuclear Information System (INIS)

    Qiang, Jun; Tao, Yi-Fan; He, Jie; Xu, Pao; Bao, Jin-Wen; Sun, Yi-Lan

    2017-01-01

    Highlights: • MiR-122 regulated tilapia MT by directly targeting MT 3′UTR. • MiR-122 level was negatively related to MT level under Cd stress. • MiR-122 silencing caused up-regulation of MT expression. • MiR-122 loss relieved liver stress and stimulated antioxidant enzymes. - Abastract: MicroRNAs (miRNAs) are small, non-coding RNAs that regulate target gene expression by binding to the 3′untranslated region (3′UTR) of the target mRNA. MiRNAs regulate a large variety of genes, including those involved in liver homeostasis and energy metabolism. Down-regulated levels of hepatic miR-122 were found in genetically improved farmed tilapia (GIFT, Oreochromis niloticus) exposed to cadmium (Cd) stress. Here, we report for the first time that reduction of miR-122 post-transcriptionally increased metallothionein (MT) mRNA levels by binding to its 3′UTR, as shown by a 3′ UTR luciferase reporter assay. The expression levels of miR-122 were negatively related to MT levels in GIFT under Cd stress. We performed in vivo functional analysis of miR-122 by injecting the fish with a miR-122 antagomir. Inhibition of miR-122 levels in GIFT liver caused a significant increase in MT expression, affected white blood cell and red blood cell counts, and serum alanine and aspartate aminotransferase activities, and glucose levels, all of which may help to relieve Cd stress-related liver stress. miR-122 silencing modulated oxidative stress and stimulated the activity of antioxidant enzymes. Our findings indicate that miR-122 regulated MT levels by binding to the 3′UTR of MT mRNA, and this interaction affected Cd stress induction and the resistance response in GIFT. We concluded that miR-122 plays an important role in regulating the stress response in GIFT liver. Our findings may contribute to understanding the mechanisms of miRNA-mediated gene regulation in tilapia in response to environmental stresses.

  1. Genetic Diversity and Selective Pressure in Hepatitis C Virus Genotypes 1-6: Significance for Direct-Acting Antiviral Treatment and Drug Resistance.

    Science.gov (United States)

    Cuypers, Lize; Li, Guangdi; Libin, Pieter; Piampongsant, Supinya; Vandamme, Anne-Mieke; Theys, Kristof

    2015-09-16

    Treatment with pan-genotypic direct-acting antivirals, targeting different viral proteins, is the best option for clearing hepatitis C virus (HCV) infection in chronically infected patients. However, the diversity of the HCV genome is a major obstacle for the development of antiviral drugs, vaccines, and genotyping assays. In this large-scale analysis, genome-wide diversity and selective pressure was mapped, focusing on positions important for treatment, drug resistance, and resistance testing. A dataset of 1415 full-genome sequences, including genotypes 1-6 from the Los Alamos database, was analyzed. In 44% of all full-genome positions, the consensus amino acid was different for at least one genotype. Focusing on positions sharing the same consensus amino acid in all genotypes revealed that only 15% was defined as pan-genotypic highly conserved (≥99% amino acid identity) and an additional 24% as pan-genotypic conserved (≥95%). Despite its large genetic diversity, across all genotypes, codon positions were rarely identified to be positively selected (0.23%-0.46%) and predominantly found to be under negative selective pressure, suggesting mainly neutral evolution. For NS3, NS5A, and NS5B, respectively, 40% (6/15), 33% (3/9), and 14% (2/14) of the resistance-related positions harbored as consensus the amino acid variant related to resistance, potentially impeding treatment. For example, the NS3 variant 80K, conferring resistance to simeprevir used for treatment of HCV1 infected patients, was present in 39.3% of the HCV1a strains and 0.25% of HCV1b strains. Both NS5A variants 28M and 30S, known to be associated with resistance to the pan-genotypic drug daclatasvir, were found in a significant proportion of HCV4 strains (10.7%). NS5B variant 556G, known to confer resistance to non-nucleoside inhibitor dasabuvir, was observed in 8.4% of the HCV1b strains. Given the large HCV genetic diversity, sequencing efforts for resistance testing purposes may need to be

  2. Real-world outcomes of unrestricted direct-acting antiviral treatment for hepatitis C in Australia: The South Australian statewide experience.

    Science.gov (United States)

    Haridy, James; Wigg, Alan; Muller, Kate; Ramachandran, Jeyamani; Tilley, Emma; Waddell, Victoria; Gordon, David; Shaw, David; Huynh, Dep; Stewart, Jeffrey; Nelson, Renjy; Warner, Morgyn; Boyd, Mark; Chinnaratha, Mohamed A; Harding, Damian; Ralton, Lucy; Colman, Anton; Liew, Danny; Iyngkaran, Guru; Tse, Edmund

    2018-06-11

    In March 2016, the Australian government offered unrestricted access to direct-acting antiviral (DAA) therapy for chronic hepatitis C (HCV) to the entire population. This included prescription by any medical practitioner in consultation with specialists until sufficient experience was attained. We sought to determine the outcomes and experience over the first twelve-months for the entire state of South Australia. We performed a prospective, observational study following outcomes of all treatments associated with the state's four main tertiary centres. 1909 subjects initiating DAA therapy were included, representing an estimated 90% of all treatments in the state. Overall, SVR12 was 80.4% in all subjects intended for treatment and 95.7% in those completing treatment and follow-up. 14.2% were lost to follow-up (LTFU) and did not complete SVR12 testing. LTFU was independently associated with community treatment via remote consultation (OR 1.50, 95% CI 1.04-2.18, p=0.03), prison-based treatment (OR 2.02, 95% CI 1.08-3.79, p=0.03) and younger age (OR 0.98, 95% CI 0.97-0.99, p=0.05). Of the 1534 subjects completing treatment and follow-up, decreased likelihood of SVR12 was associated with genotype 2 (OR 0.23,95% CI 0.07-0.74, p=0.01) and genotype 3 (OR 0.23 95% CI 0.12-0.43, p=<0.01). A significant decrease in treatment initiation was observed over the twelve-month period in conjunction with a shift from hospital to community-based treatment. Our findings support the high responses observed in clinical trials, however a significant gap exists in SVR12 in our real-world cohort due to LTFU. A declining treatment initiation rate and shift to community-based treatment highlights the need to explore additional strategies to identify, treat and follow-up remaining patients in order to achieve elimination targets. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  3. Cost-effectiveness of treating chronic hepatitis C virus with direct-acting antivirals in people who inject drugs in Australia.

    Science.gov (United States)

    Scott, Nick; Iser, David M; Thompson, Alexander J; Doyle, Joseph S; Hellard, Margaret E

    2016-04-01

    Reducing the burden of hepatitis C virus (HCV) related liver disease will require treating people who inject drugs (PWID), the group at most risk of infection and transmission. We determine the cost-effectiveness of treating PWID with interferon-free direct-acting antiviral therapy in Australia. Using a deterministic model of HCV treatment and liver disease progression, including a fixed rate of re-infection, the expected healthcare costs and quality-adjusted life years (QALYs) of a cohort of newly HCV-infected PWID were calculated for: no treatment; treatment after initial infection ("early-treatment"); and treatment prior to developing compensated cirrhosis ("late-treatment"). Incremental cost-effectiveness ratios (ICERs) were used to compare scenarios. Late-treatment was cost-effective compared to no treatment, with a discounted average gain of 2.98 (95%confidence interval 2.88-5.22) QALYs per person for an additional cost of $15,132 ($11,246-18,922), giving an ICER of $5078 ($2847-5295) per QALY gained. Compared to late-treatment, early-treatment gained a further discounted average of 2.27 (0.58-4.80) QALYs per person for $38,794 ($34,789-41,367), giving an ICER of $17,090 ($2847-63,282), which was cost-effective in approximately 90% of Monte-Carlo uncertainty simulations. For every 100 newly HCV-infected PWID, there were an estimated 40 (39-56) eventual liver-related deaths without treatment, compared to 7 (6-11) and 8 (7-13) with early-treatment and late-treatment available respectively. Treating HCV-infected PWID with new therapies is cost-effective and could prevent a significant number of liver-related deaths. Although late-treatment was the most cost-effective option, the cost per QALY gained for early-treatment compared to late-treatment is likely to be below unofficial Australian willingness to pay thresholds. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  4. miR-122 promotes hepatic antioxidant defense of genetically improved farmed tilapia (GIFT, Oreochromis niloticus) exposed to cadmium by directly targeting a metallothionein gene

    Energy Technology Data Exchange (ETDEWEB)

    Qiang, Jun, E-mail: Qiangj@ffrc.cn [Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, Jiangsu (China); Tao, Yi-Fan [Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081 (China); He, Jie [Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, Jiangsu (China); Xu, Pao, E-mail: Xup@ffrc.cn [Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, Jiangsu (China); Bao, Jin-Wen [Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081 (China); Sun, Yi-Lan [Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, Jiangsu (China)

    2017-01-15

    Highlights: • MiR-122 regulated tilapia MT by directly targeting MT 3′UTR. • MiR-122 level was negatively related to MT level under Cd stress. • MiR-122 silencing caused up-regulation of MT expression. • MiR-122 loss relieved liver stress and stimulated antioxidant enzymes. - Abastract: MicroRNAs (miRNAs) are small, non-coding RNAs that regulate target gene expression by binding to the 3′untranslated region (3′UTR) of the target mRNA. MiRNAs regulate a large variety of genes, including those involved in liver homeostasis and energy metabolism. Down-regulated levels of hepatic miR-122 were found in genetically improved farmed tilapia (GIFT, Oreochromis niloticus) exposed to cadmium (Cd) stress. Here, we report for the first time that reduction of miR-122 post-transcriptionally increased metallothionein (MT) mRNA levels by binding to its 3′UTR, as shown by a 3′ UTR luciferase reporter assay. The expression levels of miR-122 were negatively related to MT levels in GIFT under Cd stress. We performed in vivo functional analysis of miR-122 by injecting the fish with a miR-122 antagomir. Inhibition of miR-122 levels in GIFT liver caused a significant increase in MT expression, affected white blood cell and red blood cell counts, and serum alanine and aspartate aminotransferase activities, and glucose levels, all of which may help to relieve Cd stress-related liver stress. miR-122 silencing modulated oxidative stress and stimulated the activity of antioxidant enzymes. Our findings indicate that miR-122 regulated MT levels by binding to the 3′UTR of MT mRNA, and this interaction affected Cd stress induction and the resistance response in GIFT. We concluded that miR-122 plays an important role in regulating the stress response in GIFT liver. Our findings may contribute to understanding the mechanisms of miRNA-mediated gene regulation in tilapia in response to environmental stresses.

  5. Raft-mediated trafficking of apical resident proteins occurs in both direct and transcytotic pathways in polarized hepatic cells : Role of distinct lipid microdomains

    NARCIS (Netherlands)

    Slimane, TA; Trugnan, G; van Ijzendoorn, SCD; Hoekstra, D

    In polarized hepatic cells, pathways and molecular principles mediating the flow of resident apical bile canalicular proteins have not yet been resolved. Herein, we have investigated apical trafficking of a glycosylphosphatidylinositol-linked and two single transmembrane domain proteins on the one

  6. Hepatic Encephalopathy

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    Full Text Available ... to continue to work to my full capacity? Will I be able to drive? Patient Stories Angie M. Caregiver for Brother Charles DiAngelo Hepatic Encephalopathy Jason Dedmon Alcohol-related Cirrhosis ...

  7. Hepatic Encephalopathy

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    Full Text Available ... your body when your liver isn’t working well, it may affect your brain and cause HE. ... it apparent that the liver is not doing well. These could be the symptoms of Hepatic Encephalopathy ( ...

  8. Hepatic Encephalopathy

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    Full Text Available ... bad. It sends the good things – such as vitamins and nutrients – into your bloodstream for your body ... for Wife Joyce O. Caregiver for Mother Lynette K. Hepatic Encephalopathy Samantha W. Caregiver for Husband Stan ...

  9. Hepatic Encephalopathy

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    Full Text Available ... Get Worse? How is HE Diagnosed? Prior to Treatment Who treats HE? Preparing for your Medical Appointment Hepatic Encephalopathy Treatment Options Treatment Basics Treatment Medications Importance of Adhering ...

  10. Hepatic Encephalopathy

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    Full Text Available ... become familiar with the signs of Hepatic Encephalopathy so you can tell your doctor right away if ... with continuous treatment, HE can usually be controlled. So it’s important to tell your doctor about any ...

  11. Hepatic Encephalopathy

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    Full Text Available ... build-up and painful swelling of the legs (edema) and abdomen (ascites) or hepatic encephalopathy. For more ... build up and painful swelling of the legs (edema) and abdomen (ascites) Bruising and bleeding easily Enlarged ...

  12. Hepatic Encephalopathy

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    Full Text Available ... to Treatment Who treats HE? Preparing for your Medical Appointment Hepatic Encephalopathy Treatment Options Treatment Basics Treatment ... treatment. Being a fully-informed participant in your medical care is an important factor in staying as ...

  13. Hepatic Encephalopathy

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    Full Text Available ... Hepatic Encephalopathy so you can tell your doctor right away if you think you may have it. ... American Liver Foundation © 2018 American Liver Foundation. All rights reserved. Funding for the HE123 - Diagnosis, Treatment and ...

  14. Hepatic Encephalopathy

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    Full Text Available ... important for you and your family to become familiar with the signs of Hepatic Encephalopathy so you ... team evaluates the person’s overall physical and mental health, plan to pay for transplant related medical expenses, ...

  15. Hepatic Encephalopathy

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    Full Text Available ... Symptoms to look for Caregiver Support Caregiver Stories Home › What is Hepatic Encephalopathy? Why Your Liver is ... questions about HE, one step at a time. Home About Us Ways to Give Contact Us Privacy ...

  16. Hepatic Encephalopathy

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    Full Text Available ... responsible for the daily needs of another person. Caregivers can be a friend, spouse, life partner, parent, sibling or other family member. What is HE? Hepatic Encephalopathy, sometimes referred to as ...

  17. Hepatitis C

    Science.gov (United States)

    ... viral load (the amount of HCV in your blood), imaging tests, and biopsy results. Treatment is especially important for people who are showing signs liver fibrosis or scarring. Medicines used to treat hepatitis C ...

  18. Hepatic Encephalopathy

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    Full Text Available ... that can be corrected . It may also occur as part of a chronic problem from liver disease ... worse over time. Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy or PSE, is a condition that ...

  19. Hepatitis A

    Science.gov (United States)

    ... Acute liver failure requires a stay in the hospital for monitoring and treatment. Some people with acute liver failure may need a liver transplant. Prevention The hepatitis A vaccine can prevent infection with the virus. The vaccine is typically given ...

  20. Hepatic Encephalopathy

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    Full Text Available ... OVERVIEW Donate Now Join an Event Volunteer Your Time The Legacy Society Make Gifts of Stock Donate ... problem from liver disease that gets worse over time. Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy ...

  1. Hepatic Encephalopathy

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    Full Text Available ... Patient Advisory Council Media Center Careers How You Can Help OVERVIEW Donate Now Join an Event Volunteer ... Hepatic Encephalopathy is a short-term problem that can be corrected . It may also occur as part ...

  2. Hepatic Encephalopathy

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    Full Text Available ... People ALF Near You Events ALF Blogs Financial Information Policies Advocacy Patient Advisory Council Media Center Careers ... and abdomen (ascites) or hepatic encephalopathy. For more information about cirrhosis of the liver and symptoms, call ...

  3. Hepatic Encephalopathy

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    Full Text Available ... Disease (NAFLD) & Non-alcoholic Steatohepatitis (NASH) Autoimmune Hepatitis Bile duct disease such as Primary Biliary Cirrhosis (PBC) ... spleen (splenomegaly) Stone-like particles in gallbladder and bile duct (gallstones) Liver cancer (hepatocellular carcinoma) Chronic liver ...

  4. Autoimmune Hepatitis

    Science.gov (United States)

    ... hepatitis is the most common form in North America. Type 1 can occur at any age; however, ... eastern time, M-F Follow Us NIH… Turning Discovery Into Health ® Research & Funding Current Funding Opportunities Research ...

  5. Hepatic Encephalopathy

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    Full Text Available ... Hepatic Encephalopathy Treatment Options Treatment Basics Treatment Medications Importance of Adhering to Your Treatment Plan Long-Term Considerations Patient Support Finding Support Services Peer Support Groups Financial Assistance Support for My Loved Ones Resources Find ...

  6. Hepatic Encephalopathy

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    Full Text Available ... Hepatic Encephalopathy so you can tell your doctor right away if you think you may have it. ... Site Map © COPYRIGHT 2017 AMERICAN LIVER FOUNDATION. ALL RIGHTS RESERVED. Your Liver Overview

    The Faces ...

  7. Hepatic Encephalopathy

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    Full Text Available ... is a condition that causes temporary worsening of brain function in people with advanced liver disease. When ... travel through your body until they reach your brain, causing mental and physical symptoms of HE. Hepatic ...

  8. Diagnostic value of CT on hepatic tuberculosis

    International Nuclear Information System (INIS)

    Zhang Fan; Zhang Xuelin; Qiu Shijun; Zhang Yuzhong; Wen Ge; Zhong Qun

    2006-01-01

    Objective: To assess CT manifestations and diagnostic value in patients with hepatic tuberculosis. Methods: Ten cases of hepatic tuberculosis proved by hepatic biopsy or surgical specimens were analyzed retrospectively. Results: This group of hepatic tuberculosis included three types. (1) Five cases of miliary hepatic tuberculosis demonstrated that the liver swelled diffusely associated with multiple miliary low attenuations, and showed no enhancement after contrast agents administration. (2) Three cases of tubercle hepatic tuberculosis depicted multiple hypodensity areas or mixed density regions in the liver. The extension of lesions reduced in arterial phase, and a ring-like enhancement was displayed in the portal phase. (3) One case of hepatic tuberculoma illustrated solitary space occupying lesion accompanied with central necrosis. The envelope was thin and smooth which enhanced slightly after injecting Gd-DTPA. Another one was hepatic abscess and depicted fluid-fluid level inside the lesion. Conclusions: The CT manifestations of miliary hepatic tuberculosis lack of characteristics, it is hard to make the diagnosis clear-cut unless integrating the medical history and lab test. The 'powder calcification' findings of tubercle hepatic tuberculosis is propitious to draw a qualitative diagnosis. And the feature of hepatic tuberculomas with fluid- fluid level is in favor of making a differential diagnosis against parallel tumors. (authors)

  9. Direct Detection and Differentiation of Pathogenic Leptospira Species Using a Multi-Gene Targeted Real Time PCR Approach

    Science.gov (United States)

    Ferreira, Ana Sofia; Costa, Pedro; Rocha, Teresa; Amaro, Ana; Vieira, Maria Luísa; Ahmed, Ahmed; Thompson, Gertrude; Hartskeerl, Rudy A.; Inácio, João

    2014-01-01

    Leptospirosis is a growing public and veterinary health concern caused by pathogenic species of Leptospira. Rapid and reliable laboratory tests for the direct detection of leptospiral infections in animals are in high demand not only to improve diagnosis but also for understanding the epidemiology of the disease. In this work we describe a novel and simple TaqMan-based multi-gene targeted real-time PCR approach able to detect and differentiate Leptospira interrogans, L. kirschneri, L. borgpeteresenii and L. noguchii, which constitute the veterinary most relevant pathogenic species of Leptospira. The method uses sets of species-specific probes, and respective flanking primers, designed from ompL1 and secY gene sequences. To monitor the presence of inhibitors, a duplex amplification assay targeting both the mammal β-actin and the leptospiral lipL32 genes was implemented. The analytical sensitivity of all primer and probe sets was estimated to be <10 genome equivalents (GE) in the reaction mixture. Application of the amplification reactions on genomic DNA from a variety of pathogenic and non-pathogenic Leptospira strains and other non-related bacteria revealed a 100% analytical specificity. Additionally, pathogenic leptospires were successfully detected in five out of 29 tissue samples from animals (Mus spp., Rattus spp., Dolichotis patagonum and Sus domesticus). Two samples were infected with L. borgpetersenii, two with L. interrogans and one with L. kirschneri. The possibility to detect and identify these pathogenic agents to the species level in domestic and wildlife animals reinforces the diagnostic information and will enhance our understanding of the epidemiology of leptopirosis. PMID:25398140

  10. The management of metastatic radioiodine-refractory differentiated thyroid cancer requires an integrated approach including both directed and systemic therapies.

    Science.gov (United States)

    Cooray, Shamil D; Topliss, Duncan J

    2017-01-01

    A 58-year-old man with metastatic radioiodine-refractory differentiated thyroid cancer (DTC) presented with left thigh and right flank numbness. He had known progressive and widespread bony metastases, for which he received palliative radiotherapy, and multiple bilateral asymptomatic pulmonary metastases. CT scan and MRI of the spine revealed metastases at right T10-L1 vertebrae with extension into the central canal and epidural disease at T10 and T11 causing cord displacement and canal stenosis but retention of spinal cord signal. Spinal surgery was followed by palliative radiotherapy resulting in symptom resolution. Two months later, sorafenib received approval for use in Australia and was commenced and up-titrated with symptomatic management of mild adverse effects. Follow-up CT scan three months after commencement of sorafenib revealed regression of pulmonary metastases but no evident change in most bone metastases except for an advancing lesion eroding into the right acetabulum. The patient underwent a right total hip replacement, intra-lesional curettage and cementing. After six months of sorafenib therapy, CT scanning showed enlarging liver lesions with marked elevation of serum thyroglobulin. Lenvatinib was commenced and sorafenib was ceased. He now has stable disease with a falling thyroglobulin more than 5 years after metastatic radioiodine-refractory DTC was diagnosed. In DTC, 5% of distant metastases become radioiodine-refractory, resulting in a median overall survival of 2.5-3.5 years. Tyrosine kinase inhibitor (TKI) therapy has recently been demonstrated to increase progression-free survival in these patients but poses some unique management issues and is best used as part of an integrated approach with directed therapy. Directed therapies may have greater potential to control localised disease and related symptoms when compared to systemic therapies.Consider TKI therapy in progressive disease where benefits outweigh risks.Active surveillance and

  11. Hepatitis B Foundation

    Science.gov (United States)

    ... worldwide 2 Billion People have been infected with Hepatitis B Worldwide The Hepatitis B Foundation is working ... of people living with hepatitis B. Learn About Hepatitis B in 11 Other Languages . Resource Video See ...

  12. What Is Hepatitis?

    Science.gov (United States)

    ... Navigation Alt+1 Content Alt+2 What is hepatitis? Online Q&A Reviewed July 2016 Q: What ... Question and answer archives Submit a question World Hepatitis Day Posters: Eliminate hepatitis World Hepatitis Day 2017 ...

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

    Science.gov (United States)

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

  14. Auto-immune hepatitis following delivery.

    Science.gov (United States)

    Saini, Vandana; Gupta, Mamta; Mishra, S K

    2013-05-01

    Auto-immune hepatitis first presenting in the early postpartum period is rare. Immunosuppressive effects of pregnancy result in delayed manifestation of auto-immune hepatitis, and in established cases, the spontaneous improvements are there. Auto-immune hepatitis should be considered in the differential diagnosis of liver dysfunction first presenting in the early postpartum period. A case of postpartum hepatitis of auto-immune aetiology is being presented here. It is disease of unknown aetiology, characterised by inflammation of liver (as evidenced by raised serum transaminases, presence of interface hepatitis on histological examination), hypergammaglobulinaemia (> 1.5 times normal), presence of auto-antibodies [(antinuclear antibodies (ANA)], smooth muscle antibody (SMA) and antibody to liver-kidney microsome type 1 (LKM1) in the absence of viral markers ie, hepatitis B (HBsAg) and C (AntiHCV) and excellent response to corticosteroid therapy.

  15. Cell Adhesion Minimization by a Novel Mesh Culture Method Mechanically Directs Trophoblast Differentiation and Self-Assembly Organization of Human Pluripotent Stem Cells.

    Science.gov (United States)

    Okeyo, Kennedy Omondi; Kurosawa, Osamu; Yamazaki, Satoshi; Oana, Hidehiro; Kotera, Hidetoshi; Nakauchi, Hiromitsu; Washizu, Masao

    2015-10-01

    Mechanical methods for inducing differentiation and directing lineage specification will be instrumental in the application of pluripotent stem cells. Here, we demonstrate that minimization of cell-substrate adhesion can initiate and direct the differentiation of human pluripotent stem cells (hiPSCs) into cyst-forming trophoblast lineage cells (TLCs) without stimulation with cytokines or small molecules. To precisely control cell-substrate adhesion area, we developed a novel culture method where cells are cultured on microstructured mesh sheets suspended in a culture medium such that cells on mesh are completely out of contact with the culture dish. We used microfabricated mesh sheets that consisted of open meshes (100∼200 μm in pitch) with narrow mesh strands (3-5 μm in width) to provide support for initial cell attachment and growth. We demonstrate that minimization of cell adhesion area achieved by this culture method can trigger a sequence of morphogenetic transformations that begin with individual hiPSCs attached on the mesh strands proliferating to form cell sheets by self-assembly organization and ultimately differentiating after 10-15 days of mesh culture to generate spherical cysts that secreted human chorionic gonadotropin (hCG) hormone and expressed caudal-related homeobox 2 factor (CDX2), a specific marker of trophoblast lineage. Thus, this study demonstrates a simple and direct mechanical approach to induce trophoblast differentiation and generate cysts for application in the study of early human embryogenesis and drug development and screening.

  16. Effect of praziquantel on the differential expression of mouse hepatic genes and parasite ATP binding cassette transporter gene family members during Schistosoma mansoni infection.

    Directory of Open Access Journals (Sweden)

    Melissa C Sanchez

    2017-06-01

    Full Text Available Schistosomiasis is a chronic parasitic disease caused by sexually dimorphic blood flukes of the genus Schistosoma. Praziquantel (PZQ is the only drug widely available to treat the disease but does not kill juvenile parasites. Here we report the use of next generation sequencing to study the transcriptional effect of PZQ on murine hepatic inflammatory, immune and fibrotic responses to Schistosoma mansoni worms and eggs. An initial T helper cell 1 (Th1 response is induced against schistosomes in mice treated with drug vehicle (Vh around the time egg laying begins, followed by a T helper cell 2 (Th2 response and the induction of genes whose action leads to granuloma formation and fibrosis. When PZQ is administered at this time, there is a significant reduction in egg burden yet the hepatic Th1, Th2 and fibrotic responses are still observed in the absence of granuloma formation suggesting some degree of gene regulation may be induced by antigens released from the dying adult worms. Quantitative real-time PCR was used to examine the relative expression of 16 juvenile and adult S. mansoni genes during infection and their response to Vh and PZQ treatment in vivo. While the response of stress genes in adult parasites suggests the worms were alive immediately following exposure to PZQ, they were unable to induce transcription of any of the 9 genes encoding ATP-binding cassette (ABC transporters tested. In contrast, juvenile schistosomes were able to significantly induce the activities of ABCB, C and G family members, underscoring the possibility that these efflux systems play a major role in drug resistance.

  17. Liver Cancer and Hepatitis B

    Science.gov (United States)

    ... Clinical Trials Physician Directory HBV Meeting What Is Hepatitis B? What Is Hepatitis B? The ABCs of Viral Hepatitis Liver Cancer and Hepatitis B Hepatitis Delta Coinfection Hepatitis C Coinfection HIV/AIDS ...

  18. Hepatitis C: Sex and Sexuality

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

  19. Hepatitis C: Diet and Nutrition

    Science.gov (United States)

    ... with Hepatitis » Daily Living: Diet and Nutrition Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... have high cholesterol and have fatty liver. How hepatitis C affects diet If you have hepatitis, you ...

  20. Hepatitis B & C and HIV

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    ... Find Services HIV SERVICES LOCATOR Locator Search Search Hepatitis B & C Topics Hepatitis B Hepatitis C Hepatitis ... Infections Sexually Transmitted Diseases Smoking Women's Health Issues Hepatitis B Virus and Hepatitis C Virus Infection People ...

  1. Value of FibroScan in diagnosis of hepatic fibrosis in patients with HBeAg-negative chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    LUO Junhua

    2014-07-01

    Full Text Available ObjectiveTo evaluate the value of transient elastography (FibroScan, FS in predicting hepatic fibrosis in patients with HBeAg-negative chronic hepatitis B (CHB. MethodsOne hundred and four patients with HBeAg-negative CHB, who were diagnosed and treated in Hubei Hospital of Traditional Chinese Medicine from June 2011 to May 2013, were enrolled in this study. All patients underwent FS for liver stiffness measurement before liver biopsy. Statistical analysis was applied to compare liver stiffness (kPa with fibrosis stage (determined by liver biopsy. The receiver operating characteristic (ROC curve of FS was constructed, and the area under the ROC curve (AUROC was calculated to analyze the accuracy of live stiffness in predicting significant fibrosis and cirrhosis. Comparison between groups was made by Kruskal-Wallis H test, followed by Mann-Whitney U test for multiple comparisons. The correlation between two variables was analyzed by Spearman rank and Pearson correlation test. ResultsLiver stiffness gradually rose as the degree of hepatic fibrosis increased, with significant differences between groups (P<0.01 or P<0.05. Liver stiffness was positively correlated with the stage of hepatic fibrosis (r=0.810, P<0.01. The AUROC of liver stiffness for detecting liver cirrhosis was 0.956; the cut-off value for diagnosing liver cirrhosis was 13.1 kPa; the sensitivity was 92.7%, and the specificity was 80%. ConclusionFS is a promising noninvasive method for the assessment of hepatic fibrosis in patients with HBeAg-negative CHB; particularly, it has high accuracy in the diagnosis of liver cirrhosis. FS combined with direct or indirect markers may play an important role in differential diagnosis and efficacy evaluation in patients with hepatic fibrosis.

  2. [Autoimmune hepatitis].

    Science.gov (United States)

    Färkkilä, Martti

    2013-01-01

    Autoimmune hepatitis is chronic liver disease with two subtypes, type 1 with anti nuclear or smooth muscle antibodies and type 2 with LKM1 or LC1 antibodies, and both with hypergammaglobulinemia and typical histology. Prevalence of AIH is between 10 to 17 per 100000 in Europe. Up to 20-40 % of cases present with acute hepatitis. Budesonide can be used as a first line induction therapy in non-cirrhotic patients, and tiopurines, mercaptopurine or mycophenolic acid as maintenance therapies. Patients not responding to conventional therapy can be treated with ciclosporin, tacrolimus or rituximab or finally with liver transplantation.

  3. Hepatic steatosis does not cause insulin resistance in people with familial hypobetalipoproteinaemia

    NARCIS (Netherlands)

    Visser, M. E.; Lammers, N. M.; Nederveen, A. J.; van der Graaf, M.; Heerschap, A.; Ackermans, M. T.; Sauerwein, H. P.; Stroes, E. S.; Serlie, M. J.

    2011-01-01

    Hepatic steatosis is strongly associated with hepatic and whole-body insulin resistance. It has proved difficult to determine whether hepatic steatosis itself is a direct cause of insulin resistance. In patients with familial hypobetalipoproteinaemia (FHBL), hepatic steatosis is a direct consequence

  4. MicroRNA, miR-374b, directly targets Myf6 and negatively regulates C2C12 myoblasts differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Zhiyuan; Sun, Xiaorui; Xu, Dequan; Xiong, Yuanzhu; Zuo, Bo, E-mail: zuobo@mail.hzau.edu.cn

    2015-11-27

    Myogenesis is a complex process including myoblast proliferation, differentiation and myotube formation and is controlled by myogenic regulatory factors (MRFs), MyoD, MyoG, Myf5 and Myf6 (also known as MRF4). MicroRNA is a kind of ∼22 nt-long non-coding small RNAs, and act as key transcriptional or post-transcriptional regulators of gene expression. Identification of miRNAs involved in the regulation of muscle genes could improve our understanding of myogenesis process. In this study, we investigated the regulation of Myf6 gene by miRNAs. We showed that miR-374b specifically bound to the 3'untranslated region (UTR) of Myf6 and down-regulated the expression of Myf6 gene at both mRNA and protein level. Furthermore, miR-374b is ubiquitously expressed in the tissues of adult C57BL6 mouse, and the mRNA abundance increases first and then decreases during C2C12 myoblasts differentiation. Over-expression of miR-374b impaired C2C12 cell differentiation, while inhibiting miR-374b expression by 2′-O-methyl antisense oligonucleotides promoted C2C12 cell differentiation. Taken together, our findings identified miR-374b directly targets Myf6 and negatively regulates myogenesis. - Highlights: • MiR-374b directly targets 3′UTR of Myf6. • MiR-374b negatively regulates Myf6 in C2C12 cells. • MiR-374b abundance significiently changes during C2C12 cells differentiation. • MiR-374b negatively regulates C2C12 cells differentiation.

  5. Research priorities to achieve universal access to hepatitis C prevention, management and direct-acting antiviral treatment among people who inject drugs

    DEFF Research Database (Denmark)

    Grebely, Jason; Bruneau, Julie; Lazarus, Jeffrey V

    2017-01-01

    of HCV among PWID. The Kirby Institute, UNSW Sydney and the International Network on Hepatitis in Substance Users (INHSU) established an expert round table panel to assess current research gaps and establish future research priorities for the prevention and management of HCV among PWID. This round table......, gaps in research, and develop research priorities. Topics for discussion included the epidemiology of injecting drug use, HCV, and HIV among PWID, HCV prevention, HCV testing, linkage to HCV care and treatment, DAA treatment for HCV infection, and reinfection following successful treatment. This paper...

  6. Abnormal positioning of multiple abdominal organs with anomalous direct drainage of hepatic vein into the right atrium in a post operative omphalocele patient: A case report

    International Nuclear Information System (INIS)

    Hyun, Su Jeong; Cho, Bum Sang; Kim, Sung Jin; Lee, Seung Young; Kang, Min Ho; Yi, Kyung Sik

    2012-01-01

    An omphalocele is a rare congenital anomaly in which the infant's intestines protrude through the navel. Additional anomalies that are associated with omphalocele remain present in as many as 50% of cases, and these anomalies vary greatly from patient to patient. However, the persistent anomalies or abnormal position of the abdominal organs in post operative omphalocele patients have not reported previously. Herein, we report the case of an omphalocele patient with abnormal positioning of the liver, spleen and both kidneys, as well as abnormal drainage of the hepatic vein into the right atrium, which was found during a routine, postoperative follow-up computed tomography scan

  7. Hepatitis E

    Science.gov (United States)

    ... room/fact-sheets/detail/hepatitis-e","@context":"http://schema.org","@type":"Article"}; العربية 中文 français русский español ... E: recognition, investigation and control”. The manual gives information about the epidemiology, clinical manifestations of the disease, ...

  8. Hepatic haemangioma

    African Journals Online (AJOL)

    Hp 630 Dual Core

    successful usage of transhepatic compression sutures using polytetrafluoroethylene (PTFE) pledgets and selective ligation of large feeding vessels from right hepatic artery. Surgical resection may not be technically safe or possible in certain cases due to the massive or diffuse nature of the lesion, proximity to vascular ...

  9. Hepatitis B

    Science.gov (United States)

    ... which can lower your chances of developing serious health problems. Your doctor may recommend screening for hepatitis B if you ... see a doctor who specializes in liver diseases. Doctors can treat the health problems related to cirrhosis with medicines, surgery, and other ...

  10. Chronic hepatitis

    African Journals Online (AJOL)

    infection by four diagnostic systems: first generation and second generation. ELlSA, second generation recombinant immunoblot assay and nested polymerase chain reaction analysis. HepatoJogy 1992; 16: 300-305. 14. Van der Poel CL, ... Alpha-1-antitrypsin deficiency. Alcoholic hepatitis. Non-alcoholic steatohepatitis.

  11. Radiogenic hepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Rey, G; Woellgens, P; Haase, W [Katharinenhospital, Stuttgart (F.R. Germany). Strahlenklinik

    1976-08-01

    The article is about a patient who developed hepatitis after post-operative radiotherapy of a hypernephroma on the right side with /sup 60/Co ..gamma.. radiation. The scintigraph showed a normal-sized liver with parenchymal defects. Therapy consisted of anti-emetics and vitamin preparations.

  12. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Lipase Deficiency Liver Cancer Liver Cysts Non-Alcoholic Fatty Liver Disease Primary Biliary Cholangitis Primary Sclerosing Cholangitis What ... B & C Alcohol-related Liver Disease Non-alcoholic Fatty Liver Disease (NAFLD) & Non-alcoholic Steatohepatitis (NASH) Autoimmune Hepatitis ...

  13. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... of brain function in people with advanced liver disease. When your liver is damaged it can no longer remove toxic substances from your blood. These toxins build up and can travel through your body until they reach your brain, causing mental and physical symptoms of HE. Hepatic Encephalopathy often ...

  14. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... damages your liver over many years – such as long-term alcohol abuse or chronic hepatitis – can cause ... treated. It’s important to continue treatment for as long as necessary to keep HE from coming back. ...

  15. Gene expression profiling and secretome analysis differentiate adult-derived human liver stem/progenitor cells and human hepatic stellate cells.

    Directory of Open Access Journals (Sweden)

    Silvia Berardis

    Full Text Available Adult-derived human liver stem/progenitor cells (ADHLSC are obtained after primary culture of the liver parenchymal fraction. The cells are of fibroblastic morphology and exhibit a hepato-mesenchymal phenotype. Hepatic stellate cells (HSC derived from the liver non-parenchymal fraction, present a comparable morphology as ADHLSC. Because both ADHLSC and HSC are described as liver stem/progenitor cells, we strived to extensively compare both cell populations at different levels and to propose tools demonstrating their singularity. ADHLSC and HSC were isolated from the liver of four different donors, expanded in vitro and followed from passage 5 until passage 11. Cell characterization was performed using immunocytochemistry, western blotting, flow cytometry, and gene microarray analyses. The secretion profile of the cells was evaluated using Elisa and multiplex Luminex assays. Both cell types expressed α-smooth muscle actin, vimentin, fibronectin, CD73 and CD90 in accordance with their mesenchymal origin. Microarray analysis revealed significant differences in gene expression profiles. HSC present high expression levels of neuronal markers as well as cytokeratins. Such differences were confirmed using immunocytochemistry and western blotting assays. Furthermore, both cell types displayed distinct secretion profiles as ADHLSC highly secreted cytokines of therapeutic and immuno-modulatory importance, like HGF, interferon-γ and IL-10. Our study demonstrates that ADHLSC and HSC are distinct liver fibroblastic cell populations exhibiting significant different expression and secretion profiles.

  16. Hepatic progenitor cell resistance to TGF-β1's proliferative and apoptotic effects

    International Nuclear Information System (INIS)

    Clark, J. Brian; Rice, Lisa; Sadiq, Tim; Brittain, Evan; Song, Lujun; Wang Jian; Gerber, David A.

    2005-01-01

    The success of hepatocellular therapies using stem or progenitor cell populations is dependent upon multiple factors including the donor cell, microenvironment, and etiology of the liver injury. The following experiments investigated the impact of TGF-β1 on a previously described population of hepatic progenitor cells (HPC). The majority of the hepatic progenitor cells were resistant to endogenously produced TGF-β1's proapoptotic and anti-proliferative effects unlike more well-differentiated cellular populations (e.g., mature hepatocytes). Surprisingly, in vitro TGF-β1 supplementation significantly inhibited de novo hepatic progenitor cell colony formation possibly via an indirect mechanism(s). Therefore despite the HPC's direct resistance to supplemental TGF-β1, this cytokine's inhibitory effect on colony formation could have a potential negative impact on the use of these cells as a therapy for patients with liver disease

  17. Aging Reduces an ERRalpha-Directed Mitochondrial Glutaminase Expression Suppressing Glutamine Anaplerosis and Osteogenic Differentiation of Mesenchymal Stem Cells.

    Science.gov (United States)

    Huang, Tongling; Liu, Renzhong; Fu, Xuekun; Yao, Dongsheng; Yang, Meng; Liu, Qingli; Lu, William W; Wu, Chuanyue; Guan, Min

    2017-02-01

    Aging deteriorates osteogenic capacity of mesenchymal stem/stromal cells (MSCs), contributing to imbalanced bone remodeling and osteoporosis. Glutaminase (Gls) catabolizes glutamine into glutamate at the first step of mitochondrial glutamine (Gln)-dependent anaplerosis which is essential for MSCs upon osteogenic differentiation. Estrogen-related receptor α (ERRα) regulates genes required for mitochondrial function. Here, we found that ERRα and Gls are upregulated by osteogenic induction in human MSCs (hMSCs). In contrast, osteogenic differentiation capacity and glutamine consumption of MSCs, as well as ERRα, Gls and osteogenic marker genes are significantly reduced with age. We demonstrated that ERRα binds to response elements on Gls promoter and affects glutamine anaplerosis through transcriptional induction of Gls. Conversely, mTOR inhibitor rapamycin, ERRα inverse agonist compound 29 or Gls inhibitor BPTES leads to reduced Gln anaplerosis and deteriorated osteogenic differentiation of hMSCs. Importantly, overexpression of ERRα or Gls restored impairment by these inhibitors. Finally, we proved that compensated ERRα or Gls expression indeed potentiated Gln anaplerosis and osteogenic capability of elderly mice MSCs in vitro. Together, we establish that Gls is a novel ERRα target gene and ERRα/Gls signaling pathway plays an important role in osteogenic differentiation of MSCs, providing new sights into novel regenerative therapeutics development. Our findings suggest that restoring age-related mitochondrial Gln-dependent anaplerosis may be beneficial for degenerative bone disorders such as osteoporosis. Stem Cells 2017;35:411-424. © 2016 AlphaMed Press.

  18. Micro-/Nano- sized hydroxyapatite directs differentiation of rat bone marrow derived mesenchymal stem cells towards an osteoblast lineage

    Science.gov (United States)

    Huang, Yan; Zhou, Gang; Zheng, Lisha; Liu, Haifeng; Niu, Xufeng; Fan, Yubo

    2012-03-01

    Regenerative medicine consisting of cells and materials provides a new way for the repair and regeneration of tissues and organs. Nano-biomaterials are highlighted due to their advantageous features compared with conventional micro-materials. The aim of this study is to investigate the effects of micro-/nano- sized hydroxyapatite (μ/n-HA) on the osteogenic differentiation of rat bone marrow derived mesenchymal stem cells (rBMSCs). μ/n-HA were prepared by a microwave synthesizer and precipitation method, respectively. Different sizes of μ/n-HA were characterized by IR, XRD, SEM, TEM and co-cultured with rBMSCs. It was shown that rBMSCs expressed higher levels of osteoblast-related markers by n-HA than μ-HA stimulation. The size of HA is an important factor for affecting the osteogenic differentiation of rBMSCs. This provides a new avenue for mechanistic studies of stem cell differentiation and a new approach to obtain more committed differentiated cells.

  19. Hepatic amebiasis

    Directory of Open Access Journals (Sweden)

    Salles José Maria

    2003-01-01

    Full Text Available Amebiasis can be considered the most aggressive disease of the human intestine, responsible in its invasive form for clinical syndromes, ranging from the classic dysentery of acute colitis to extra-intestinal disease, with emphasis on hepatic amebiasis, unsuitably named amebic liver abscess. Found worldwide, with a high incidence in India, tropical regions of Africa, Mexico and other areas of Central America, it has been frequently reported in Amazonia. The trophozoite reaches the liver through the portal system, provoking enzymatic focal necrosis of hepatocytes and multiple micro-abscesses that coalesce to develop a single lesion whose central cavity contains a homogeneous thick liquid, with typically reddish brown and yellow color similar to "anchovy paste". Right upper quadrant pain, fever and hepatomegaly are the predominant symptoms of hepatic amebiasis. Jaundice is reported in cases with multiple lesions or a very large abscess, and it affects the prognosis adversely. Besides chest radiography, ultrasonography and computerized tomography have brought remarkable contributions to the diagnosis of hepatic abscesses. The conclusive diagnosis is made however by the finding of Entamoeba histolytica trophozoites in the pus and by the detection of serum antibodies to the amoeba. During the evolution of hepatic amebiasis, in spite of the availability of highly effective drugs, some important complications may occur with regularity and are a result of local perforation with extension into the pleural and pericardium cavities, causing pulmonary abscesses and purulent pericarditis, respectively The ruptures into the abdominal cavity may lead to subphrenic abscesses and peritonitis. The treatment of hepatic amebiasis is made by medical therapy, with metronidazole as the initial drug, followed by a luminal amebicide. In patients with large abscesses, showing signs of imminent rupture, and especially those who do not respond to medical treatment, a

  20. Hepatic amebiasis

    Directory of Open Access Journals (Sweden)

    José Maria Salles

    Full Text Available Amebiasis can be considered the most aggressive disease of the human intestine, responsible in its invasive form for clinical syndromes, ranging from the classic dysentery of acute colitis to extra-intestinal disease, with emphasis on hepatic amebiasis, unsuitably named amebic liver abscess. Found worldwide, with a high incidence in India, tropical regions of Africa, Mexico and other areas of Central America, it has been frequently reported in Amazonia. The trophozoite reaches the liver through the portal system, provoking enzymatic focal necrosis of hepatocytes and multiple micro-abscesses that coalesce to develop a single lesion whose central cavity contains a homogeneous thick liquid, with typically reddish brown and yellow color similar to "anchovy paste". Right upper quadrant pain, fever and hepatomegaly are the predominant symptoms of hepatic amebiasis. Jaundice is reported in cases with multiple lesions or a very large abscess, and it affects the prognosis adversely. Besides chest radiography, ultrasonography and computerized tomography have brought remarkable contributions to the diagnosis of hepatic abscesses. The conclusive diagnosis is made however by the finding of Entamoeba histolytica trophozoites in the pus and by the detection of serum antibodies to the amoeba. During the evolution of hepatic amebiasis, in spite of the availability of highly effective drugs, some important complications may occur with regularity and are a result of local perforation with extension into the pleural and pericardium cavities, causing pulmonary abscesses and purulent pericarditis, respectively The ruptures into the abdominal cavity may lead to subphrenic abscesses and peritonitis. The treatment of hepatic amebiasis is made by medical therapy, with metronidazole as the initial drug, followed by a luminal amebicide. In patients with large abscesses, showing signs of imminent rupture, and especially those who do not respond to medical treatment, a

  1. PKR is a novel functional direct player that coordinates skeletal muscle differentiation via p38MAPK/AKT pathways.

    Science.gov (United States)

    Alisi, A; Spaziani, A; Anticoli, S; Ghidinelli, M; Balsano, C

    2008-03-01

    Myogenic differentiation is a highly orchestrated multistep process controlled by extracellular growth factors that modulate largely unknown signals into the cell affecting the muscle-transcription program. P38MAPK-dependent signalling, as well as PI3K/Akt pathway, has a key role in the control of muscle gene expression at different stages during the myogenic process. P38MAPK affects the activities of transcription factors, such as MyoD and myogenin, and contributes, together with PI3K/Akt pathway, to control the early and late steps of myogenic differentiation. The aim of our work was to better define the role of PKR, a dsRNA-activated protein kinase, as potential component in the differentiation program of C2C12 murine myogenic cells and to correlate its activity with p38MAPK and PI3K/Akt myogenic regulatory pathways. Here, we demonstrate that PKR is an essential component of the muscle development machinery and forms a functional complex with p38MAPK and/or Akt, contributing to muscle differentiation of committed myogenic cells in vitro. Inhibition of endogenous PKR activity by a specific (si)RNA and a PKR dominant-negative interferes with the myogenic program of C2C12 cells, causing a delay in activation of myogenic specific genes and inducing the formation of thinner myofibers. In addition, the construction of three PKR mutants allowed us to demonstrate that both N and C-terminal regions of PKR are critical for the interaction with p38MAPK and Akt. The novel discovered complex permits PKR to timely regulate the inhibition/activation of p38MAPK and Akt, controlling in this way the different steps characterizing skeletal muscle differentiation.

  2. Counter-attack on viral hepatitis. [Hepatitis A; Hepatitis B

    Energy Technology Data Exchange (ETDEWEB)

    Prozesky, O W [Pretoria Univ. (South Africa). Dept. of Medical Virology; Jupp, P G; Joubert, J J; Taylor, M B; Grabow, W O.K.

    1985-07-01

    The most highly developed radioimmunoassay test system in medical virology is proving of exceptional value in research aimed at controlling and eventually eradicating the scourge of human hepatitis. The use of radioimmunoassay in detecting hepatitis A (HAV) and hepatitis B (HBV) viruses is discussed. The hepatitis A virus is an enterovirus which infects the gastrointestinal tract and is usually transmitted by contaminated food, milk or water. Hepatitis B spreads mainly by the parenteral rate. Bedbugs and ticks are considered as possible transmitters of HBV. Another important contribution of radioimmunoassay is the ability to monitor the immune response of persons at risk who are vaccinated against hepatitis B.

  3. Cytokine-free directed differentiation of human pluripotent stem cells efficiently produces hemogenic endothelium with lymphoid potential.

    Science.gov (United States)

    Galat, Yekaterina; Dambaeva, Svetlana; Elcheva, Irina; Khanolkar, Aaruni; Beaman, Kenneth; Iannaccone, Philip M; Galat, Vasiliy

    2017-03-17

    The robust generation of human hematopoietic progenitor cells from induced or embryonic pluripotent stem cells would be beneficial for multiple areas of research, including mechanistic studies of hematopoiesis, the development of cellular therapies for autoimmune diseases, induced transplant tolerance, anticancer immunotherapies, disease modeling, and drug/toxicity screening. Over the past years, significant progress has been made in identifying effective protocols for hematopoietic differentiation from pluripotent stem cells and understanding stages of mesodermal, endothelial, and hematopoietic specification. Thus, it has been shown that variations in cytokine and inhibitory molecule treatments in the first few days of hematopoietic differentiation define primitive versus definitive potential of produced hematopoietic progenitor cells. The majority of current feeder-free, defined systems for hematopoietic induction from pluripotent stem cells include prolonged incubations with various cytokines that make the differentiation process complex and time consuming. We established that the application of Wnt agonist CHIR99021 efficiently promotes differentiation of human pluripotent stem cells in the absence of any hematopoietic cytokines to the stage of hemogenic endothelium capable of definitive hematopoiesis. The hemogenic endothelium differentiation was accomplished in an adherent, serum-free culture system by applying CHIR99021. Hemogenic endothelium progenitor cells were isolated on day 5 of differentiation and evaluated for their endothelial, myeloid, and lymphoid potential. Monolayer induction based on GSK3 inhibition, described here, yielded a large number of CD31 + CD34 + hemogenic endothelium cells. When isolated and propagated in adherent conditions, these progenitors gave rise to mature endothelium. When further cocultured with OP9 mouse stromal cells, these progenitors gave rise to various cells of myeloid lineages as well as natural killer lymphoid, T

  4. Hepatitis B (HBV)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Hepatitis B KidsHealth / For Teens / Hepatitis B What's in ... Prevented? Print en español Hepatitis B What Is Hepatitis B? Hepatitis B is an infection of the ...

  5. Hepatitis A Vaccine

    Science.gov (United States)

    Twinrix® (as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... Why get vaccinated against hepatitis A?Hepatitis A is a serious liver disease. It is caused by the hepatitis A virus (HAV). HAV is spread from ...

  6. Directed Differentiation of Human Embryonic Stem Cells into Prostate Organoids In Vitro and its Perturbation by Low-Dose Bisphenol A Exposure.

    Directory of Open Access Journals (Sweden)

    Esther L Calderon-Gierszal

    Full Text Available Studies using rodent and adult human prostate stem-progenitor cell models suggest that developmental exposure to the endocrine disruptor Bisphenol-A (BPA can predispose to prostate carcinogenesis with aging. Unknown at present is whether the embryonic human prostate is equally susceptible to BPA during its natural developmental window. To address this unmet need, we herein report the construction of a pioneer in vitro human prostate developmental model to study the effects of BPA. The directed differentiation of human embryonic stem cells (hESC into prostatic organoids in a spatial system was accomplished with precise temporal control of growth factors and steroids. Activin-induced definitive endoderm was driven to prostate specification by combined exposure to WNT10B and FGF10. Matrigel culture for 20-30 days in medium containing R-Spondin-1, Noggin, EGF, retinoic acid and testosterone was sufficient for mature prostate organoid development. Immunofluorescence and gene expression analysis confirmed that organoids exhibited cytodifferentiation and functional properties of the human prostate. Exposure to 1 nM or 10 nM BPA throughout differentiation culture disturbed early morphogenesis in a dose-dependent manner with 1 nM BPA increasing and 10 nM BPA reducing the number of branched structures formed. While differentiation of branched structures to mature organoids seemed largely unaffected by BPA exposure, the stem-like cell population increased, appearing as focal stem cell nests that have not properly entered lineage commitment rather than the rare isolated stem cells found in normally differentiated structures. These findings provide the first direct evidence that low-dose BPA exposure targets hESC and perturbs morphogenesis as the embryonic cells differentiate towards human prostate organoids, suggesting that the developing human prostate may be susceptible to disruption by in utero BPA exposures.

  7. Identification of ERdj3 and OBF-1/BOB-1/OCA-B as direct targets of XBP-1 during plasma cell differentiation.

    Science.gov (United States)

    Shen, Ying; Hendershot, Linda M

    2007-09-01

    Plasma cell differentiation is accompanied by a modified unfolded protein response (UPR), which involves activation of the Ire1 and activating transcription factor 6 branches, but not the PKR-like endoplasmic reticulum kinase branch. Ire1-mediated splicing of XBP-1 (XBP-1(S)) is required for terminal differentiation, although the direct targets of XBP-1(S) in this process have not been identified. We demonstrate that XBP-1(S) binds to the promoter of ERdj3 in plasmacytoma cells and in LPS-stimulated primary splenic B cells, which corresponds to increased expression of ERdj3 transcripts in both cases. When small hairpin RNA was used to decrease XBP-1 expression in plasmacytoma lines, ERdj3 transcripts were concomitantly reduced. The accumulation of Ig gamma H chain protein was also diminished, but unexpectedly this occurred at the transcriptional level as opposed to effects on H chain stability. The decrease in H chain transcripts correlated with a reduction in mRNA encoding the H chain transcription factor, OBF-1/BOB-1/OCA-B. Chromatin immunoprecipitation experiments revealed that XBP-1(S) binds to the OBF-1/BOB-1/OCA-B promoter in the plasmacytoma line and in primary B cells not only during plasma cell differentiation, but also in response to classical UPR activation. Gel shift assays suggest that XBP-1(S) binding occurs through a UPR element conserved in both murine and human OBF-1/BOB-1/OCA-B promoters as opposed to endoplasmic reticulum stress response elements. Our studies are the first to identify direct downstream targets of XBP-1(S) during either plasma cell differentiation or the UPR. In addition, our data further define the XBP-1(S)-binding sequence and provide yet another role for this protein as a master regulator of plasma cell differentiation.

  8. Persistent Rule-Following in the Face of Reversed Reinforcement Contingencies: The Differential Impact of Direct Versus Derived Rules.

    Science.gov (United States)

    Harte, Colin; Barnes-Holmes, Yvonne; Barnes-Holmes, Dermot; McEnteggart, Ciara

    2017-11-01

    Rule-governed behavior and its role in generating insensitivity to direct contingencies of reinforcement have been implicated in human psychological suffering. In addition, the human capacity to engage in derived relational responding has also been used to explain specific human maladaptive behaviors, such as irrational fears. To date, however, very little research has attempted to integrate research on contingency insensitivity and derived relations. The current work sought to fill this gap. Across two experiments, participants received either a direct rule (Direct Rule Condition) or a rule that involved a novel derived relational response (Derived Rule Condition). Provision of a direct rule resulted in more persistent rule-following in the face of competing contingencies, but only when the opportunity to follow the reinforced rule beforehand was relatively protracted. Furthermore, only in the Direct Rule Condition were there significant correlations between rule-compliance and stress. A post hoc interpretation of the findings is provided.

  9. Matrix-directed differentiation of human adipose-derived mesenchymal stem cells to dermal-like fibroblasts that produce extracellular matrix.

    Science.gov (United States)

    Sivan, Unnikrishnan; Jayakumar, K; Krishnan, Lissy K

    2016-10-01

    Commercially available skin substitutes lack essential non-immune cells for adequate tissue regeneration of non-healing wounds. A tissue-engineered, patient-specific, dermal substitute could be an attractive option for regenerating chronic wounds, for which adipose-derived mesenchymal stem cells (ADMSCs) could become an autologous source. However, ADMSCs are multipotent in nature and may differentiate into adipocytes, osteocytes and chondrocytes in vitro, and may develop into undesirable tissues upon transplantation. Therefore, ADMSCs committed to the fibroblast lineage could be a better option for in vitro or in vivo skin tissue engineering. The objective of this study was to standardize in vitro culture conditions for ADMSCs differentiation into dermal-like fibroblasts which can synthesize extracellular matrix (ECM) proteins. Biomimetic matrix composite, deposited on tissue culture polystyrene (TCPS), and differentiation medium (DM), supplemented with fibroblast-conditioned medium and growth factors, were used as a fibroblast-specific niche (FSN) for cell culture. For controls, ADMSCs were cultured on bare TCPS with either DM or basal medium (BM). Culture of ADMSCs on FSN upregulated the expression of differentiation markers such as fibroblast-specific protein-1 (FSP-1) and a panel of ECM molecules specific to the dermis, such as fibrillin-1, collagen I, collagen IV and elastin. Immunostaining showed the deposition of dermal-specific ECM, which was significantly higher in FSN compared to control. Fibroblasts derived from ADMSCs can synthesize elastin, which is an added advantage for successful skin tissue engineering as compared to fibroblasts from skin biopsy. To obtain rapid differentiation of ADMSCs to dermal-like fibroblasts for regenerative medicine, a matrix-directed differentiation strategy may be employed. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

  10. Development and molecular composition of the hepatic progenitor cell niche.

    Science.gov (United States)

    Vestentoft, Peter Siig

    2013-05-01

    , we examined several genes upregulated in a global gene expression array conducted on one of these models, in which progenitor cells are activated. The protein expression patterns were evaluated in our collections of human embryonic and fetal livers, human liver diseases, and rodent hepatic injury models. When analyzing standard histological liver sections underlying connections and tissue architecture are not immediately evident. We therefore developed models for digitally reconstructing not only protein expression in serially cut tissue sections, but also vessels of the portal area. Article I constituted our earliest attempts to create 3D reconstructions of biological material. Human embryonic stem cell cultures were previously thought to consist of homogenously undifferentiated cells. The protocols for 3D reconstructions developed in this study demonstrated micro heterogeneity in expression of differentiation markers and provided the basis for later reconstructions of hepatic tissues. In article II we examined the expression patterns of chosen proteins seen upregulated in the gene array as well as classical hepatocytic and cholangiocytic markers in human liver disease and during prenatal development. Previous studies had indicated direct connections between activated progenitor cells apparently isolated in the parenchyma and the intrahepatic biliary tree. Our developed protocols for 3D reconstructions visually demonstrated direct connections between these entities. Analysis of protein expression in prenatal liver revealed the formation of the intrahepatic tree to occur through a special form of asymmetric tubulogenesis, only recently described in mice. In order to describe the composition of the hepatic progenitor cell niche and the localization of cell surface proteins in article III, the expression patterns of certain genes upregulated in the gene array analysis were analyzed in different models of rodent liver regeneration. We observed that the extracellular

  11. Neural patterning of human induced pluripotent stem cells in 3-D cultures for studying biomolecule-directed differential cellular responses.

    Science.gov (United States)

    Yan, Yuanwei; Bejoy, Julie; Xia, Junfei; Guan, Jingjiao; Zhou, Yi; Li, Yan

    2016-09-15

    Appropriate neural patterning of human induced pluripotent stem cells (hiPSCs) is critical to generate specific neural cells/tissues and even mini-brains that are physiologically relevant to model neurological diseases. However, the capacity of signaling factors that regulate 3-D neural tissue patterning in vitro and differential responses of the resulting neural populations to various biomolecules have not yet been fully understood. By tuning neural patterning of hiPSCs with small molecules targeting sonic hedgehog (SHH) signaling, this study generated different 3-D neuronal cultures that were mainly comprised of either cortical glutamatergic neurons or motor neurons. Abundant glutamatergic neurons were observed following the treatment with an antagonist of SHH signaling, cyclopamine, while Islet-1 and HB9-expressing motor neurons were enriched by an SHH agonist, purmorphamine. In neurons derived with different neural patterning factors, whole-cell patch clamp recordings showed similar voltage-gated Na(+)/K(+) currents, depolarization-evoked action potentials and spontaneous excitatory post-synaptic currents. Moreover, these different neuronal populations exhibited differential responses to three classes of biomolecules, including (1) matrix metalloproteinase inhibitors that affect extracellular matrix remodeling; (2) N-methyl-d-aspartate that induces general neurotoxicity; and (3) amyloid β (1-42) oligomers that cause neuronal subtype-specific neurotoxicity. This study should advance our understanding of hiPSC self-organization and neural tissue development and provide a transformative approach to establish 3-D models for neurological disease modeling and drug discovery. Appropriate neural patterning of human induced pluripotent stem cells (hiPSCs) is critical to generate specific neural cells, tissues and even mini-brains that are physiologically relevant to model neurological diseases. However, the capability of sonic hedgehog-related small molecules to tune

  12. AUTOIMMUNE HEPATITIS

    Directory of Open Access Journals (Sweden)

    Yusri Dianne Jurnalis

    2010-05-01

    Full Text Available AbstrakHepatitis autoimun merupakan penyakit inflamasi hati yang berat dengan penyebab pasti yang tidak diketahui yang mengakibatkan morbiditas dan mortalitas yang tinggi. Semua usia dan jenis kelamin dapat dikenai dengan insiden tertinggi pada anak perempuan usia prepubertas, meskipun dapat didiagnosis pada usia 6 bulan. Hepatitis autoimun dapat diklasifikasikan menjadi 2 bagian berdasarkan adanya antibodi spesifik: Smooth Muscle Antibody (SMA dengan anti-actin specificity dan/atau Anti Nuclear Antibody (ANA pada tipe 1 dan Liver-Kidney Microsome antibody (LKM1 dan/atau anti-liver cytosol pada tipe 2. Gambaran histologisnya berupa “interface hepatitis”, dengan infiltrasi sel mononuklear pada saluran portal, berbagai tingkat nekrosis, dan fibrosis yang progresf. Penyakit berjalan secara kronik tetapi keadaan yang berat biasanya menjadi sirosis dan gagal hati.Tipe onset yang paling sering sama dengan hepatitis virus akut dengan gagal hati akut pada beberapa pasien; sekitar sepertiga pasien dengan onset tersembunyi dengan kelemahan dan ikterik progresif ketika 10-15% asimptomatik dan mendadak ditemukan hepatomegali dan/atau peningkatan kadar aminotransferase serum. Adanya predominasi perempuan pada kedua tipe. Pasien LKM1 positif menunjukkan keadaan lebih akut, pada usia yang lebih muda, dan biasanya dengan defisiensi Immunoglobulin A (IgA, dengan durasi gejala sebelum diagnosis, tanda klinis, riwayat penyakit autoimun pada keluarga, adanya kaitan dengan gangguan autoimun, respon pengobatan dan prognosis jangka panjang sama pada kedua tipe.Kortikosteroid yang digunakan secara tunggal atau kombinasi azathioprine merupakan terapi pilihan yang dapat menimbulkan remisi pada lebih dari 90% kasus. Strategi terapi alternatif adalah cyclosporine. Penurunan imunosupresi dikaitkan dengan tingginya relap. Transplantasi hati dianjurkan pada penyakit hati dekom-pensata yang tidak respon dengan pengobatan medis lainnya.Kata kunci : hepatitis Autoimmune

  13. Improved differentiation between hepatic hemangioma and metastases on diffusion-weighted MRI by measurement of standard deviation of apparent diffusion coefficient.

    Science.gov (United States)

    Hardie, Andrew D; Egbert, Robert E; Rissing, Michael S

    2015-01-01

    Diffusion-weighted magnetic resonance imaging (DW-MR) can be useful in the differentiation of hemangiomata from liver metastasis, but improved methods other than by mean apparent diffusion coefficient (mADC) are needed. A retrospective review identified 109 metastatic liver lesions and 86 hemangiomata in 128 patients who had undergone DW-MR. For each lesion, mADC and the standard deviation of the mean ADC (sdADC) were recorded and compared by receiver operating characteristic analysis. Mean mADC was higher in benign hemangiomata (1.52±0.12 mm(2)/s) than in liver metastases (1.33±0.18 mm(2)/s), but there was significant overlap in values. The mean sdADC was lower in hemangiomata (101±17 mm(2)/s) than metastases (245±25 mm(2)/s) and demonstrated no overlap in values, which was significantly different (P<.0001). Hemangiomata may be better able to be differentiated from liver metastases on the basis of sdADC than by mADC, although further studies are needed. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Differential expression of candidate virus receptors in human T lymphocytes prone or resistant to infection with patient-derived hepatitis C virus.

    Directory of Open Access Journals (Sweden)

    Mohammed A Sarhan

    Full Text Available Accumulated evidence implies that hepatitis C virus (HCV infects not only the liver but also the immune system. A lymphocyte-specific CD5 molecule was recently identified as essential for infection of T cells with native, patient-derived HCV. To assess whether the proposed hepatocyte receptors may also contribute to HCV lymphotropism, expression of scavenger receptor-class B type 1 (SR-B1, claudin-1 (CLDN-1, claudin-6 (CLDN-6, occludin (OCLN, CD5 and CD81 was examined by real-time RT-PCR and the respective proteins quantified by immunoblotting in HCV-prone and resistant T cell lines, peripheral blood mononuclear cells (PBMC, primary T cells and their subsets, and compared to hepatoma Huh7.5 and HepG2 cells. SR-B1 protein was found in T and hepatoma cell lines but not in PBMC or primary T lymphocytes, CLDN-1 in HCV-resistant PM1 T cell line and hepatoma cells only, while CLDN-6 equally in the cells investigated. OCLN protein occurred in HCV-susceptible Molt4 and Jurkat T cells and its traces in primary T cells, but not in PBMC. CD5 was displayed by HCV-prone T cell lines, primary T cells and PBMC, but not by non-susceptible T and hepatoma cell lines, while CD81 in all cell types except HepG2. Knocking-down OCLN in virus-prone T cell line inhibited HCV infection, while de novo infection downregulated OCLN and CD81, and upregulated CD5 without modifying SR-B1 expression. Overall, while no association between SR-B1, CLDN-1 or CLDN-6 and the susceptibility to HCV was found, CD5 and CD81 expression coincided with virus lymphotropism and that of OCLN with permissiveness of T cell lines but unlikely primary T cells. This study narrowed the range of factors potentially utilized by HCV to infect T lymphocytes amongst those uncovered using laboratory HCV and Huh7.5 cells. Together with the demonstrated role for CD5 in HCV lymphotropism, the findings indicate that virus utilizes different molecules to enter hepatocytes and lymphocytes.

  15. Hepatic (Liver) Function Panel

    Science.gov (United States)

    ... Educators Search English Español Blood Test: Hepatic (Liver) Function Panel KidsHealth / For Parents / Blood Test: Hepatic (Liver) ... kidneys ) is working. What Is a Hepatic (Liver) Function Panel? A liver function panel is a blood ...

  16. Hepatitis C and Incarceration

    Science.gov (United States)

    ... Hepatitis Cdo to take care of their liver? People with Hepatitis C should not use alcohol or street drugs, as these can hurt the liver. Some other products can also hurt people with Hepatitis C, even if they appear to ...

  17. Hepatitis B virus (image)

    Science.gov (United States)

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

  18. Hepatitis Risk Assessment

    Science.gov (United States)

    ... please visit this page: About CDC.gov . Hepatitis Risk Assessment Recommend on Facebook Tweet Share Compartir Viral Hepatitis. Are you at risk? Take this 5 minute Hepatitis Risk Assessment developed ...

  19. Nonmuscle myosin IIA and IIB differentially contribute to intrinsic and directed migration of human embryonic lung fibroblasts.

    Science.gov (United States)

    Kuragano, Masahiro; Murakami, Yota; Takahashi, Masayuki

    2018-03-25

    Nonmuscle myosin II (NMII) plays an essential role in directional cell migration. In this study, we investigated the roles of NMII isoforms (NMIIA and NMIIB) in the migration of human embryonic lung fibroblasts, which exhibit directionally persistent migration in an intrinsic manner. NMIIA-knockdown (KD) cells migrated unsteadily, but their direction of migration was approximately maintained. By contrast, NMIIB-KD cells occasionally reversed their direction of migration. Lamellipodium-like protrusions formed in the posterior region of NMIIB-KD cells prior to reversal of the migration direction. Moreover, NMIIB KD led to elongation of the posterior region in migrating cells, probably due to the lack of load-bearing stress fibers in this area. These results suggest that NMIIA plays a role in steering migration by maintaining stable protrusions in the anterior region, whereas NMIIB plays a role in maintenance of front-rear polarity by preventing aberrant protrusion formation in the posterior region. These distinct functions of NMIIA and NMIIB might promote intrinsic and directed migration of normal human fibroblasts. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Activation of protein kinase A and exchange protein directly activated by cAMP promotes adipocyte differentiation of human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Jia, Bingbing; Madsen, Lise; Petersen, Rasmus Koefoed

    2012-01-01

    ) and exchange protein directly activated by cAMP (Epac) in adipocyte conversion of human mesenchymal stem cells derived from adipose tissue (hMADS). We show that cAMP signaling involving the simultaneous activation of both PKA- and Epac-dependent signaling is critical for this process even in the presence......Human mesenchymal stem cells are primary multipotent cells capable of differentiating into several cell types including adipocytes when cultured under defined in vitro conditions. In the present study we investigated the role of cAMP signaling and its downstream effectors, protein kinase A (PKA...... results emphasize the need for cAMP signaling in concert with treatment with a PPARγ or PPARδ agonist to secure efficient adipocyte differentiation of human hMADS mesenchymal stem cells....

  1. Hepatitis B Vaccine

    Science.gov (United States)

    ... a combination product containing Haemophilus influenzae type b, Hepatitis B Vaccine) ... combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis, Hepatitis B, Polio Vaccine)

  2. The excretory-secretory products of Echinococcus granulosus protoscoleces directly regulate the differentiation of B10, B17 and Th17 cells.

    Science.gov (United States)

    Pan, Wei; Hao, Wen-Ting; Shen, Yu-Juan; Li, Xiang-Yang; Wang, Yan-Juan; Sun, Fen-Fen; Yin, Jian-Hai; Zhang, Jing; Tang, Ren-Xian; Cao, Jian-Ping; Zheng, Kui-Yang

    2017-07-21

    Excretory-secretory products (ESPs) released by helminths are well-known to regulate T cell responses in the host. However, their direct influence in the differentiation of naïve T cells, and especially B cells, remains largely unknown. This study investigated the effects of Echinococcus granulosus protoscoleces ESPs (EgPSC-ESPs) on the differentiation of IL-10-producing B cells (B10), IL-17A-producing B cells (B17) and Th17 cells. BALB/c mice injected with EgPSC were used to evaluate the in vivo profiles of B10, B17 and Th17 cells. In vitro purified CD19 + B and naïve CD4 + T cells were cultured in the presence of native, heat-inactivated or periodate-treated EgPSC-ESPs, and the differentiation of these cell subsets were compared. In contrast to the control group, infected mice showed higher frequencies of B10, B17 and Th17 cells, and higher levels of IL-10 and IL-17A in the sera. Interestingly, B17 cells were first identified to express CD19 + CD1d high . In vitro, B cells cultured with native ESPs exhibited a higher percentage of B10 cells but lower percentage of B17 and Th17 cells compared to the PBS group. Moreover, the relative expression of IL-10 and IL-17A mRNA were consistent with the altered frequencies. However, ESPs subjected to heat-inactivation or periodate treatment exhibited an inverse effect on the induction of these cell subsets. Our findings indicate that ESPs released by EgPSC can directly regulate the differentiation of B10, B17 and Th17 cells, which appear to be heat-labile and carbohydrate-dependent.

  3. Topographical cues of direct metal laser sintering titanium surfaces facilitate osteogenic differentiation of bone marrow mesenchymal stem cells through epigenetic regulation.

    Science.gov (United States)

    Zheng, Guoying; Guan, Binbin; Hu, Penghui; Qi, Xingying; Wang, Pingting; Kong, Yu; Liu, Zihao; Gao, Ping; Li, Rui; Zhang, Xu; Wu, Xudong; Sui, Lei

    2018-04-27

    To investigate the role of hierarchical micro/nanoscale topography of direct metal laser sintering (DMLS) titanium surfaces in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), as well as the possible underlying epigenetic mechanism. Three groups of titanium specimens were prepared, including DMLS group, sandblasted, large-grit, acid-etched (SLA) group and smooth titanium (Ti) group. BMSCs were cultured on discs followed by surface characterization. Cell adhesion and proliferation were examined by SEM and CCK-8 assay, while osteogenic-related gene expression was detected by real-time RT-PCR. Immunofluorescence, western blotting and in vivo study were also performed to evaluate the potential for osteogenic induction of materials. In addition, to investigate the underlying epigenetic mechanisms, immunofluorescence and western blotting were performed to evaluate the global level of H3K4me3 during osteogenesis. The H3K4me3 and H3K27me3 levels at the promoter area of the osteogenic gene Runx2 were detected by ChIP assay. The DMLS surface exhibits greater protein adsorption ability and shows better cell adhesion performance than SLA and Ti surfaces. Moreover, both in vitro and in vivo studies demonstrated that the DMLS surface is more favourable for the osteogenic differentiation of BMSCs than SLA and Ti surfaces. Accordingly, osteogenesis-associated gene expression in BMSCs is efficiently induced by a rapid H3K27 demethylation and increase in H3K4me3 levels at gene promoters upon osteogenic differentiation on DMLS titanium surface. Topographical cues of DMLS surfaces have greater potential for the induction of osteogenic differentiation of BMSCs than SLA and Ti surfaces both in vitro and in vivo. A potential epigenetic mechanism is that the appropriate topography allows rapid H3K27 demethylation and an increased H3K4me3 level at the promoter region of osteogenesis-associated genes during the osteogenic differentiation of BMSCs. © 2018 John Wiley

  4. Direct effects of casein phosphopeptides on growth and differentiation of in vitro cultured osteoblastic cells (MC3T3-E1).

    Science.gov (United States)

    Tulipano, Giovanni; Bulgari, Omar; Chessa, Stefania; Nardone, Alessandro; Cocchi, Daniela; Caroli, Anna

    2010-02-25

    Casein phosphopeptides (CPPs) obtained by enzymatic hydrolysis in vitro of caseins, have been shown to enhance calcium solubility and to increase the calcification of embryonic rat bones in their diaphyseal area. Little is known about the direct effects of CPPs on cultured osteoblastic cells. Calcium in the microenvironment surrounding bone cells is not only important for the mineralization of the extracellular matrix, but it is believed to provide preosteblasts with a signal that modulates their proliferation and differentiation. The aim of the present study was to investigate the direct effects of four selected casein phosphopeptides on osteoblastic cell (MC3T3-E1 cells) viability and differentiation. The selected peptides have been obtained by chemical synthesis and differed in the number of phosphorylated sites and in the amino acid spacing out two phosphorylated sites, in order to further characterize the relationship between structure and function. The results obtained in this work demonstrated that CPPs may directly affect osteoblast-like cell growth, calcium uptake and ultimately calcium deposition in the extracellular matrix. The effects exerted by distinct CPPs on osteogenesis in vitro can be either stimulatory or inhibitory. Differential short amino acid sequences in their molecules, like the -SpEE- and the -SpTSpEE-motifs, are likely the molecular determinants for their biological activities on osteoblastic cells. Moreover, two genetic variants of CPPs showing one amino acid change in their sequence may profoundly differ in their biological activities. Finally, our data may also suggest important clues about the role of intrinsic phosphorylated peptides derived from endogenous phosphorylated proteins in bone metabolism, apart from extrinsic CPPs. Copyright 2009 Elsevier B.V. All rights reserved.

  5. Differential loggerhead by-catch and direct mortality due to surface longlines according to boat strata and gear type

    Directory of Open Access Journals (Sweden)

    Juan A. Camiñas

    2006-12-01

    Full Text Available Surface longline gears are used to fish different species, mainly albacore Thunnus alalunga (Bonnaterre, 1788, bluefin tuna Thunnus thynnus (Linnaeus, 1758, and swordfish Xiphias gladius Linnaeus, 1758, and are considered highly dangerous for threatened marine turtles. Loggerheads Caretta caretta (Linnaeus, 1758 can be incidentally captured by surface longlines. A number of captured individuals die during the fishing operation, which we consider direct mortality due to fishing. We analysed the relative loggerhead by-catch and direct mortality associated with each type of boat and gear from April to December during the period 1999-2004 in the Spanish surface longline fleet that fishes in the western Mediterranean Sea, an important fishing area for this fleet. We used different indices to compute the catch per unit effort (CPUE according to the number of hooks and to the number of fishing operations for each type of boat and gear. Both by-catch and direct mortality differed significantly according to the type of boat and gear. With respect to the number of hooks, boats longer than 12 m not using a roller and targeting bluefin tuna captured the highest number of loggerheads, whereas boats longer than 12 m with a roller that targeted swordfish caused the highest direct mortality. With respect to the number of fishing operations, boats longer than 12 m without a roller that targeted albacore captured the highest number of loggerheads; the highest direct mortality was caused by this type of boat and by boats longer than 12 m using a roller and targeting swordfish.

  6. Cell culture-adaptive mutations of NS5A affect replication of hepatitis C virus differentially depending on the viral genotypes.

    Science.gov (United States)

    Chung, Aeri; Jin, Bora; Han, Kwang-Hyub; Ahn, Sang Hoon; Kim, Seungtaek

    2017-01-01

    Most of HCV RNAs require cell culture-adaptive mutations for efficient replication in cell culture and a number of such mutations have been described including a well-known S2204I substitution mutation in NS5A protein. In contrast, the replication of genotype 2a JFH1 RNA in cell culture does not require any cell culture-adaptive mutation. Rather, the presence of S2204I mutation impaired the JFH1 RNA replication. In this study, we examined the effect of reversions and substitutions of NS5A cell culture-adaptive mutations on virus replication in different genotypic backgrounds after either placing genotype 1a NS5A in the genotype 2a JFH1 or vice versa. The results from this investigation suggest that the S2204I mutation affects HCV RNA replication differentially depending on the viral genotypes but that the effect was not simply explained by the genotypic background. Perhaps, the effect of the S2204I mutation on HCV replication reflects both intra- and intergenic interactions of NS5A protein. J. Med. Virol. 89:146-152, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Direct and indirect methods for the determination of vitamin K3 using differential pulse polarography and application to pharmaceuticals.

    Science.gov (United States)

    Somer, Güler; Doğan, Mehmet

    2008-11-01

    Two methods for the determination of vitamin K(3) have been developed. Vitamin K(3) in its oxidized form is determined by direct and indirect methods. Its standard solution was prepared by the indirect method using Ti(III) as reducing agent. For this purpose vitamin K(3) (menadion) in a clinical injection solution, which is in its hydroquinone form in the presence of sulfite, is oxidized with oxygen. In 0.2 M HAc and 0.02 M HCl electrolyte vitamin K(3) and Ti(IV) have reduction peaks at -0.58 V at -0.82 V respectively. The reaction between Ti(III) and vitamin takes place quantitatively in a medium of 0.2 M HAc and 0.002 M HCl. After the reduction, the reaction product Ti(IV) is followed from its polarographic peak at about -0.82 V. The most important result in this work is that, with this method vitamin K(3) can be standardized and after standardization this solution can be used for the direct determination in routine analysis with a very simple and fast method, using only the peak at -0.71 V in 0.2 M HAc medium. Both direct and indirect methods have been used for the determination of Vitamin K(3) in a clinical injection solution. The limit of quantification (LOQ) was 1.5x10(-6) M and in both methods the detection limit found was 7x10(-7) M.

  8. Hematopoietic stem cell capture and directional differentiation into vascular endothelial cells for metal stent-coated chitosan/hyaluronic acid loading CD133 antibody.

    Science.gov (United States)

    Zhang, Shixuan; Zhang, Fan; Feng, Bo; Fan, Qingyu; Yang, Feng; Shang, Debin; Sui, Jinghan; Zhao, Hong

    2015-03-01

    A series of metal stents coated with chitosan/hyaluronic acid (CS/HA) loading antibodies by electrostatic self-assembled method were prepared, and the types of cells captured by antibodies and their differentiation in vascular endothelial cells (ECs) evaluated by molecular biology and scanning electron microscope. The results showed that CD133 stent can selectively capture hematopoietic stem cells (HSC),which directionally differentiate into vascular ECs in peripheral blood by (CS/HA) induction, and simultaneously inhibit migration and proliferation of immune cells and vascular smooth muscle cells (MCs). CD34 stent can capture HSC, hematopoietic progenitor cells that differentiate into vascular ECs and immune cells, promoting smooth MCs growth, leading to thrombosis, inflammation, and rejection. CD133 stent can be implanted into miniature pig heart coronary and can repair vascular damage by capturing own HSC, thus contributing to the rapid natural vascular repair, avoiding inflammation and rejection, thrombosis and restenosis. These studies demonstrated that CD133 stent of HSC capture will be an ideal coated metal stent providing a new therapeutic approach for cardiovascular and cerebrovascular disease.

  9. A direct method for numerical solution of a class of nonlinear Volterra integro-differential equations and its application to the nonlinear fission and fusion reactor kinetics

    International Nuclear Information System (INIS)

    Nakahara, Yasuaki; Ise, Takeharu; Kobayashi, Kensuke; Itoh, Yasuyuki

    1975-12-01

    A new method has been developed for numerical solution of a class of nonlinear Volterra integro-differential equations with quadratic nonlinearity. After dividing the domain of the variable into subintervals, piecewise approximations are applied in the subintervals. The equation is first integrated over a subinterval to obtain the piecewise equation, to which six approximate treatments are applied, i.e. fully explicit, fully implicit, Crank-Nicolson, linear interpolation, quadratic and cubic spline. The numerical solution at each time step is obtained directly as a positive root of the resulting algebraic quadratic equation. The point reactor kinetics with a ramp reactivity insertion, linear temperature feedback and delayed neutrons can be described by one of this type of nonlinear Volterra integro-differential equations. The algorithm is applied to the Argonne benchmark problem and a model problem for a fast reactor without delayed neutrons. The fully implicit method has been found to be unconditionally stable in the sense that it always gives the positive real roots. The cubic spline method is divergent, and the other four methods are intermediate in between. From the estimation of the stability, convergency, accuracy and CPU time, it is concluded that the Crank-Nicolson method is best, then the linear interpolation method comes closely next to it. Discussions are also made on the possibility of applying the algorithm to the fusion reactor kinetics in the form of a nonlinear partial differential equation. (auth.)

  10. Atomic force microscopy reveals a morphological differentiation of chromobacterium violaceum cells associated with biofilm development and directed by N-hexanoyl-L-homoserine lactone.

    Directory of Open Access Journals (Sweden)

    Anara A Kamaeva

    Full Text Available Chromobacterium violaceum abounds in soil and water ecosystems in tropical and subtropical regions and occasionally causes severe and often fatal human and animal infections. The quorum sensing (QS system and biofilm formation are essential for C. violaceum's adaptability and pathogenicity, however, their interrelation is still unknown. C. violaceum's cell and biofilm morphology were examined by atomic force microscopy (AFM in comparison with growth rates, QS-dependent violacein biosynthesis and biofilm biomass quantification. To evaluate QS regulation of these processes, the wild-type strain C. violaceum ATCC 31532 and its mini-Tn5 mutant C. violaceum NCTC 13274, cultivated with and without the QS autoinducer N-hexanoyl-L-homoserine lactone (C6-HSL, were used. We report for the first time the unusual morphological differentiation of C. violaceum cells, associated with biofilm development and directed by the QS autoinducer. AFM revealed numerous invaginations of the external cytoplasmic membrane of wild-type cells, which were repressed in the mutant strain and restored by exogenous C6-HSL. With increasing bacterial growth, polymer matrix extrusions formed in place of invaginations, whereas mutant cells were covered with a diffusely distributed extracellular substance. Thus, quorum sensing in C. violaceum involves a morphological differentiation that organises biofilm formation and leads to a highly differentiated matrix structure.

  11. Atomic force microscopy reveals a morphological differentiation of chromobacterium violaceum cells associated with biofilm development and directed by N-hexanoyl-L-homoserine lactone.

    Science.gov (United States)

    Kamaeva, Anara A; Vasilchenko, Alexey S; Deryabin, Dmitry G

    2014-01-01

    Chromobacterium violaceum abounds in soil and water ecosystems in tropical and subtropical regions and occasionally causes severe and often fatal human and animal infections. The quorum sensing (QS) system and biofilm formation are essential for C. violaceum's adaptability and pathogenicity, however, their interrelation is still unknown. C. violaceum's cell and biofilm morphology were examined by atomic force microscopy (AFM) in comparison with growth rates, QS-dependent violacein biosynthesis and biofilm biomass quantification. To evaluate QS regulation of these processes, the wild-type strain C. violaceum ATCC 31532 and its mini-Tn5 mutant C. violaceum NCTC 13274, cultivated with and without the QS autoinducer N-hexanoyl-L-homoserine lactone (C6-HSL), were used. We report for the first time the unusual morphological differentiation of C. violaceum cells, associated with biofilm development and directed by the QS autoinducer. AFM revealed numerous invaginations of the external cytoplasmic membrane of wild-type cells, which were repressed in the mutant strain and restored by exogenous C6-HSL. With increasing bacterial growth, polymer matrix extrusions formed in place of invaginations, whereas mutant cells were covered with a diffusely distributed extracellular substance. Thus, quorum sensing in C. violaceum involves a morphological differentiation that organises biofilm formation and leads to a highly differentiated matrix structure.

  12. Directing chondrogenic differentiation of mesenchymal stem cells with a solid-supported chitosan thermogel for cartilage tissue engineering

    International Nuclear Information System (INIS)

    Huang, Hongjie; Zhang, Xin; Hu, Xiaoqing; Dai, Linghui; Zhu, Jingxian; Man, Zhentao; Ao, Yingfang; Chen, Haifeng; Zhou, Chunyan

    2014-01-01

    Hydrogels are attractive for cartilage tissue engineering because of their high plasticity and similarity with the native cartilage matrix. However, one critical drawback of hydrogels for osteochondral repair is their inadequate mechanical strength. To address this limitation, we constructed a solid-supported thermogel comprising a chitosan hydrogel system and demineralized bone matrix. Scanning electron microscopy, the equilibrium scanning ratio, the biodegradation rate, biomechanical tests, biochemical assays, metabolic activity tests, immunostaining and cartilage-specific gene expression analysis were used to evaluate the solid-supported thermogel. Compared with pure hydrogel or demineralized matrix, the hybrid biomaterial showed superior porosity, equilibrium swelling and degradation rate. The hybrid scaffolds exhibited an increased mechanical strength: 75% and 30% higher compared with pure hydrogels and demineralized matrix, respectively. After three days culture, bone-derived mesenchymal stem cells (BMSCs) maintained viability above 90% in all three materials; however, the cell retention of the hybrid scaffolds was more efficient and uniform than the other materials. Matrix production and chondrogenic differentiation of BMSCs in the hybrid scaffolds were superior to its precursors, based on glycosaminoglycan quantification and hyaline cartilage marker expression after three weeks in culture. Its easy preparation, favourable biophysical properties and chondrogenic capacity indicated that this solid-supported thermogel could be an attractive biomaterial framework for cartilage tissue engineering. (paper)

  13. Comparison between traditional and goal directed perfusion in cardiopulmonary by-pass. Adaptation of a differential cost analysis

    Directory of Open Access Journals (Sweden)

    Massimiliano Povero

    2015-10-01

    Full Text Available BACKGROUND: A previous patient-level discrete event simulation (DES model was developed to perform an economic evaluation of GDP strategy with respect to TP in US. Aim of this supplement is provide results of the adaptations of the differential cost analysis to Belgium, Canada, France, Germany, Italy, and UK. METHODS: A Discrete Event Simulation model was developed to compare TP and GDP strategy in patients undergoing CPB. National perspective was adopted to calculate costs associated to each event while GDP strategy was exploited the introduction of Sorin Heartlink (HL Card/GDP Card and Sorin Connect (electronic data management system. RESULTS: GDP reduces the total cost with respect to traditional perfusion; furthermore the cost of GDP strategy (Sorin GDPTM Monitor and Sorin ConnectTM is completely offset by the saving in hospital stay. CONCLUSION: GDP seems to improve significantly the main outcomes related to CPB surgery, when compared to TP techniques. Additional costs due to perform GDP strategy have no impact on the total cost since completely offset by the savings in hospital cost.

  14. Application of Serum Hepatic Fibrosis Indices in the Diagnosis of Hepatic Disease

    International Nuclear Information System (INIS)

    Lu Yanting; Wang Taisong; Gu Xin

    2010-01-01

    To investigate the significance of combined detection of laminin (LN), collagen type IV (CIV), hyaluronic acid (HA) and precollagen type III (PCIII) in the diagnosis of hepatic fibrosis. The serum levels of LN, CIV, HA and PCIII in 143 patients with hepatic disease and 41 healthy controls were measured by radioimmunoassay (RIA). The results showed that the serum levels of LN, CIV, HA and PCIII in patients with hepatic disease were significantly higher than those of the control group (P<0.01), and the serum levels of those markers were related to the severity of the chronic hepatic disease. The highest serum levels were found in serious chronic hepatitis group and hepatic fibrosis group,and the increase of serum HA and PCIII was most remarkable. Combined detection of LN, CIV, HA and PCIII is a sensitive and reliable method in the diagnosis of hepatic fibrosis, but the four serum indices can not be used in differentiating serious chronic hepatitis and hepatic fibrosis. (authors)

  15. Action of DTPA on hepatic plutonium. III. Evidence for a direct chelation mechanism for DTPA-induced excretion of monomeric plutonium into rat bile

    International Nuclear Information System (INIS)

    Bhattacharyya, M.H.; Peterson, D.P.

    1979-01-01

    Trisodium calcium diethylenetriaminepenta[2- 14 C]acetic acid ([ 14 C]DTPA, 0.25 nmole/kg, 0.210 mCi/mmole) was administered via the jugular vein to three rats whose bile ducts and urinary bladders were cannulated. Bile and urine were collected for 24 h after injection, and tissues and excreta were then analyzed for 14 C content. [ 14 C]DTPA was identified in the bile samples by cochromatography with unlabeled DTPA on an anion-exchange column system. Data from this experiment demonstrated the existence of a minor excretion pathway for DTPA into rat bile, accounting for 0.12% of the injected dose by 24 h after administration. Bile was collected for 24 h following the administration of unlabeled Na 3 [CaDTPA] (0.25 mmole/kg, iv) to a rat which had received 239 Pu(IV)-citrate (5.7 μCi/kg, iv) 24 h prior to DTPA. Bile samples containing Pu were analyzed using anion-exchange column chromatography. Eighty to ninety percent of the Pu present in bile chromatographed as a single peak in the position of the Pu-DTPA complex. Cochromatograhy of the 0- to 6-h bile sample with a 239 Pu-[ 14 C]DTPA complex revealed that the Pu appearing in bile following DTPA treatment comigrated with the 239 Pu-[ 14 C]DTPA complex. These data provide strong evidence that, in the rat, DTPA acts to remove hepatic deposits of monomeric Pu by formation of the Pu-DTPA complex followed by excretion of the complex into bile

  16. miR-122 promotes hepatic antioxidant defense of genetically improved farmed tilapia (GIFT, Oreochromis niloticus) exposed to cadmium by directly targeting a metallothionein gene.

    Science.gov (United States)

    Qiang, Jun; Tao, Yi-Fan; He, Jie; Xu, Pao; Bao, Jin-Wen; Sun, Yi-Lan

    2017-01-01

    MicroRNAs (miRNAs) are small, non-coding RNAs that regulate target gene expression by binding to the 3'untranslated region (3'UTR) of the target mRNA. MiRNAs regulate a large variety of genes, including those involved in liver homeostasis and energy metabolism. Down-regulated levels of hepatic miR-122 were found in genetically improved farmed tilapia (GIFT, Oreochromis niloticus) exposed to cadmium (Cd) stress. Here, we report for the first time that reduction of miR-122 post-transcriptionally increased metallothionein (MT) mRNA levels by binding to its 3'UTR, as shown by a 3' UTR luciferase reporter assay. The expression levels of miR-122 were negatively related to MT levels in GIFT under Cd stress. We performed in vivo functional analysis of miR-122 by injecting the fish with a miR-122 antagomir. Inhibition of miR-122 levels in GIFT liver caused a significant increase in MT expression, affected white blood cell and red blood cell counts, and serum alanine and aspartate aminotransferase activities, and glucose levels, all of which may help to relieve Cd stress-related liver stress. miR-122 silencing modulated oxidative stress and stimulated the activity of antioxidant enzymes. Our findings indicate that miR-122 regulated MT levels by binding to the 3'UTR of MT mRNA, and this interaction affected Cd stress induction and the resistance response in GIFT. We concluded that miR-122 plays an important role in regulating the stress response in GIFT liver. Our findings may contribute to understanding the mechanisms of miRNA-mediated gene regulation in tilapia in response to environmental stresses. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. The Potential Impact of a Hepatitis C Vaccine for People Who Inject Drugs: Is a Vaccine Needed in the Age of Direct-Acting Antivirals?

    Directory of Open Access Journals (Sweden)

    Jack Stone

    Full Text Available The advent of highly effective hepatitis C (HCV treatments has questioned the need for a vaccine to control HCV amongst people who inject drugs (PWID. However, high treatment costs and ongoing reinfection risk suggest it could still play a role. We compared the impact of HCV vaccination amongst PWID against providing HCV treatment.Dynamic HCV vaccination and treatment models among PWID were used to determine the vaccination and treatment rates required to reduce chronic HCV prevalence or incidence in the UK over 20 or 40 years. Projections considered a low (50% protection for 5 years, moderate (70% protection for 10 years or high (90% protection for 20 years efficacy vaccine. Sensitivities to various parameters were examined.To halve chronic HCV prevalence over 40 years, the low, moderate and high efficacy vaccines required annual vaccination rates (coverage after 20 years of 162 (72%, 77 (56% and 44 (38% per 1000 PWID, respectively. These vaccination rates were 16, 7.6 and 4.4 times greater than corresponding treatment rates. To halve prevalence over 20 years nearly doubled these vaccination rates (moderate and high efficacy vaccines only and the vaccination-to-treatment ratio increased by 20%. For all scenarios considered, required annual vaccination rates and vaccination-to-treatment ratios were at least a third lower to reduce incidence than prevalence. Baseline HCV prevalence had little effect on the vaccine's impact on prevalence or incidence, but substantially affected the vaccination-to-treatment ratios. Behavioural risk heterogeneity only had an effect if we assumed no transitions between high and low risk states and vaccinations were targeted or if PWID were high risk for their first year.Achievable coverage levels of a low efficacy prophylactic HCV vaccine could greatly reduce HCV transmission amongst PWID. Current high treatment costs ensure vaccination could still be an important intervention option.

  18. Highly efficient reprogramming to pluripotency and directed differentiation of human cells using synthetic modified mRNA

    OpenAIRE

    Warren, Luigi; Manos, Philip D.; Ahfeldt, Tim; Loh, Yuin-Han; Li, Hu; Lau, Frank; Ebina, Wataru; Mandal, Pankaj; Smith, Zachary D.; Meissner, Alexander; Daley, George Q.; Brack, Andrew S.; Collins, James J.; Cowan, Chad; Schlaeger, Thorsten M.

    2010-01-01

    Clinical application of induced pluripotent stem (iPS) cells is limited by the low efficiency of iPS derivation and the fact that most protocols modify the genome to effect cellular reprogramming. Moreover, safe and effective means of directing the fate of patient-specific iPS cells towards clinically useful cell types are lacking. Here we describe a simple, non-integrating strategy for reprogramming cell fate based on administration of synthetic mRNA modified to overcome innate anti-viral re...

  19. HIV and Viral Hepatitis

    Science.gov (United States)

    ... common causes of viral hepatitis are hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV). HBV and HCV are common ... gov/ mmwr/ preview/ mmwrhtml/ rr5516a1. htm? s_ cid= rr5516a1_ e. The Numbers • • Of people with HIV in the ...

  20. Object-directed imitation in autism spectrum disorder is differentially influenced by motoric task complexity, but not social contextual cues.

    Science.gov (United States)

    Chetcuti, Lacey; Hudry, Kristelle; Grant, Megan; Vivanti, Giacomo

    2017-11-01

    We examined the role of social motivation and motor execution factors in object-directed imitation difficulties in autism spectrum disorder. A series of to-be-imitated actions was presented to 35 children with autism spectrum disorder and 20 typically developing children on an Apple ® iPad ® by a socially responsive or aloof model, under conditions of low and high motor demand. There were no differences in imitation performance (i.e. the number of actions reproduced within a fixed sequence), for either group, in response to a model who acted socially responsive or aloof. Children with autism spectrum disorder imitated the high motor demand task more poorly than the low motor demand task, while imitation performance for typically developing children was equivalent across the low and high motor demand conditions. Furthermore, imitative performance in the autism spectrum disorder group was unrelated to social reciprocity, though positively associated with fine motor coordination. These results suggest that difficulties in object-directed imitation in autism spectrum disorder are the result of motor execution difficulties, not reduced social motivation.

  1. Differential Effects of Systemic Cholinergic Receptor Blockade on Pavlovian Incentive Motivation and Goal-Directed Action Selection

    Science.gov (United States)

    Ostlund, Sean B; Kosheleff, Alisa R; Maidment, Nigel T

    2014-01-01

    Reward-seeking actions can be guided by external cues that signal reward availability. For instance, when confronted with a stimulus that signals sugar, rats will prefer an action that produces sugar over a second action that produces grain pellets. Action selection is also sensitive to changes in the incentive value of potential rewards. Thus, rats that have been prefed a large meal of sucrose will prefer a grain-seeking action to a sucrose-seeking action. The current study investigated the dependence of these different aspects of action selection on cholinergic transmission. Hungry rats were given differential training with two unique stimulus-outcome (S1-O1 and S2-O2) and action-outcome (A1-O1 and A2-O2) contingencies during separate training phases. Rats were then given a series of Pavlovian-to-instrumental transfer tests, an assay of cue-triggered responding. Before each test, rats were injected with scopolamine (0, 0.03, or 0.1 mg/kg, intraperitoneally), a muscarinic receptor antagonist, or mecamylamine (0, 0.75, or 2.25 mg/kg, intraperitoneally), a nicotinic receptor antagonist. Although the reward-paired cues were capable of biasing action selection when rats were tested off-drug, both anticholinergic treatments were effective in disrupting this effect. During a subsequent round of outcome devaluation testing—used to assess the sensitivity of action selection to a change in reward value—we found no effect of either scopolamine or mecamylamine. These results reveal that cholinergic signaling at both muscarinic and nicotinic receptors mediates action selection based on Pavlovian reward expectations, but is not critical for flexibly selecting actions using current reward values. PMID:24370780

  2. Evaluation of the biomarker candidate MFAP4 for non-invasive assessment of hepatic fibrosis in hepatitis C patients.

    Science.gov (United States)

    Bracht, Thilo; Mölleken, Christian; Ahrens, Maike; Poschmann, Gereon; Schlosser, Anders; Eisenacher, Martin; Stühler, Kai; Meyer, Helmut E; Schmiegel, Wolff H; Holmskov, Uffe; Sorensen, Grith L; Sitek, Barbara

    2016-07-04

    The human microfibrillar-associated protein 4 (MFAP4) is located to extracellular matrix fibers and plays a role in disease-related tissue remodeling. Previously, we identified MFAP4 as a serum biomarker candidate for hepatic fibrosis and cirrhosis in hepatitis C patients. The aim of the present study was to elucidate the potential of MFAP4 as biomarker for hepatic fibrosis with a focus on the differentiation of no to moderate (F0-F2) and severe fibrosis stages and cirrhosis (F3 and F4, Desmet-Scheuer scoring system). MFAP4 levels were measured using an AlphaLISA immunoassay in a retrospective study including n = 542 hepatitis C patients. We applied a univariate logistic regression model based on MFAP4 serum levels and furthermore derived a multivariate model including also age and gender. Youden-optimal cutoffs for binary classification were determined for both models without restrictions and considering a lower limit of 80 % sensitivity (correct classification of F3 and F4), respectively. To assess the generalization error, leave-one-out cross validation (LOOCV) was performed. MFAP4 levels were shown to differ between no to moderate fibrosis stages F0-F2 and severe stages (F3 and F4) with high statistical significance (t test on log scale, p value <2.2·10(-16)). In the LOOCV, the univariate classification resulted in 85.8 % sensitivity and 54.9 % specificity while the multivariate model yielded 81.3 % sensitivity and 61.5 % specificity (restricted approaches). We confirmed the applicability of MFAP4 as a novel serum biomarker for assessment of hepatic fibrosis and identification of high-risk patients with severe fibrosis stages in hepatitis C. The combination of MFAP4 with existing tests might lead to a more accurate non-invasive diagnosis of hepatic fibrosis and allow a cost-effective disease management in the era of new direct acting antivirals.

  3. Bullous pemphigoid associated with chronic hepatitis C virus infection in a hepatitis B virus endemic area: A case report.

    Science.gov (United States)

    Jang, Hyunil; Jin, Young-Joo; Yoon, Chang Hwi; Kim, Cheol-Woo; Kim, Lucia

    2018-04-01

    Bullous pemphigoid is a type of acute or chronic autoimmune disease that involves subepidermal skin lesions with bulla formation. Although viral infections, such as, human herpes virus (HHV), human immunodeficiency virus, cytomegalovirus, Epstein-Barr virus, HHV-6, hepatitis B virus (HBV), and hepatitis C virus (HCV), are known factors of bullous pemphigoid, HCV infection has only been rarely associated factor, especially in HBV endemic area. A 78-year-old man was admitted to our hospital due to erythematous bulla of onset 3 months before presentation affecting his entire body. Pathologic findings, that is, subepidermal bullae containing eosinophils and neutrophils with superficial perivascular lymphocytic and eosinophilic infiltration, were consistent with bullous pemphigoid. Anti-HCV was positive and HCV quantitative real-time polymerase chain reaction (PCR) was 1.25 x 10 IU/mL. HCV genotype was 2a. After a diagnosis of bullous pemphigoid associated with chronic HCV infection was reached, he was treated with oral methylprednisolone for bullous pemphigoid, and his skin lesions improved. Oral direct-acting antiviral agents (sofosbuvir plus ribavirin) were prescribed for chronic hepatitis C, and sustained viral response was achieved. The authors report a rare case of bullous pemphigoid associated with chronic HCV infection in a HBV endemic area and advise that HCV should be considered in the differential diagnosis of factors precipitating bullous pemphigoid, even in HBV endemic areas.

  4. Hepatic radiography

    International Nuclear Information System (INIS)

    Bernardino, M.E.; Sones, P.J.

    1985-01-01

    The past several years have seen significant advances in diagnostic and interventional radiology. These advances have been particularly rewarding for the study of liver disease. Improved imaging and therapeutic procedures in oncology have generated changes in treatment protocols and in evaluating the results of therapy for hepatic malignancies. The enriched understanding of the anatomic and hemodynamic aspects of the portal system has greatly benefited patients with portal hypertension. Now physicians are confidently more aggressive in the therapeutic approach to the variceal bleeder, and they have modified their approach to the preservation of portal flow following shunt. All of the diagnostic modalities used to evaluate the liver are represented in this book. In its structure and organization this volume goes beyond a historical overview of imaging to present greater insight into the current state of the art, as well as possible future developments. Each chapter is designed to elucidate the advantages and weaknesses of the various diagnostic modalities

  5. Parvovirus B19 Associated Hepatitis

    Science.gov (United States)

    Bihari, Chhagan; Rastogi, Archana; Saxena, Priyanka; Rangegowda, Devraj; Chowdhury, Ashok; Gupta, Nalini; Sarin, Shiv Kumar

    2013-01-01

    Parvovirus B19 infection can present with myriads of clinical diseases and syndromes; liver manifestations and hepatitis are examples of them. Parvovirus B19 hepatitis associated aplastic anemia and its coinfection with other hepatotropic viruses are relatively underrecognized, and there is sufficient evidence in the literature suggesting that B19 infections can cause a spectrum of liver diseases from elevation of transaminases to acute hepatitis to fulminant liver failure and even chronic hepatitis. It can also cause fatal macrophage activation syndrome and fibrosing cholestatic hepatitis. Parvovirus B19 is an erythrovirus that can only be replicate in pronormoblasts and hepatocytes, and other cells which have globosides and glycosphingolipids in their membrane can also be affected by direct virus injury due to nonstructural protein 1 persistence and indirectly by immune mediated injury. The virus infection is suspected in bone marrow aspiration in cases with sudden drop of hemoglobin and onset of transient aplastic anemia in immunosuppressed or immunocompetent patients and is confirmed either by IgM and IgG positive serology, PCR analysis, and in situ hybridization in biopsy specimens or by application of both. There is no specific treatment for parvovirus B19 related liver diseases, but triple therapy regimen may be effective consisting of immunoglobulin, dehydrohydrocortisone, and cyclosporine. PMID:24232179

  6. Determinants of DHA levels in early infancy: differential effects of breast milk and direct fish oil supplementation.

    Science.gov (United States)

    Meldrum, S J; D'Vaz, N; Casadio, Y; Dunstan, J A; Niels Krogsgaard-Larsen, N; Simmer, K; Prescott, S L

    2012-06-01

    Although omega (n)-3 long-chain polyunsaturated fatty acids (LCPUFA), particularly docosahexaenoic acid (DHA), intakes are important during infancy, the optimal method of increasing infant status remains unclear. We hypothesized that high-dose infant fish oil supplementation would have greater relative effects upon n-3 LCPUFA status at six months of age than breast milk fatty acids. Infants (n=420) were supplemented daily from birth to six months with fish oil or placebo. In a subset of infants, LCPUFA levels were measured in cord blood, breast milk and in infant blood at 6 months. DHA levels increased in the fish oil group relative to placebo (p<05). Breast milk DHA was the strongest predictor of infant erythrocyte DHA levels (p=<001). This remained significant after adjustment for cord blood DHA, supplementation group and adherence. In this cohort, breast milk DHA was a greater determinant of infant erythrocyte n-3 LCPUFA status, than direct supplementation with fish oil. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Differential sensory cortical involvement in auditory and visual sensorimotor temporal recalibration: Evidence from transcranial direct current stimulation (tDCS).

    Science.gov (United States)

    Aytemür, Ali; Almeida, Nathalia; Lee, Kwang-Hyuk

    2017-02-01

    Adaptation to delayed sensory feedback following an action produces a subjective time compression between the action and the feedback (temporal recalibration effect, TRE). TRE is important for sensory delay compensation to maintain a relationship between causally related events. It is unclear whether TRE is a sensory modality-specific phenomenon. In 3 experiments employing a sensorimotor synchronization task, we investigated this question using cathodal transcranial direct-current stimulation (tDCS). We found that cathodal tDCS over the visual cortex, and to a lesser extent over the auditory cortex, produced decreased visual TRE. However, both auditory and visual cortex tDCS did not produce any measurable effects on auditory TRE. Our study revealed different nature of TRE in auditory and visual domains. Visual-motor TRE, which is more variable than auditory TRE, is a sensory modality-specific phenomenon, modulated by the auditory cortex. The robustness of auditory-motor TRE, unaffected by tDCS, suggests the dominance of the auditory system in temporal processing, by providing a frame of reference in the realignment of sensorimotor timing signals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Differential effects of bifrontal and occipital nerve stimulation on pain and fatigue using transcranial direct current stimulation in fibromyalgia patients.

    Science.gov (United States)

    To, Wing Ting; James, Evan; Ost, Jan; Hart, John; De Ridder, Dirk; Vanneste, Sven

    2017-07-01

    Fibromyalgia is a disorder characterized by widespread musculoskeletal pain frequently accompanied by other symptoms such as fatigue. Moderate improvement from pharmacological and non-pharmacological treatments have proposed non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) to the occipital nerve (more specifically the C2 area) or to the dorsolateral prefrontal cortex (DLPFC) as potential treatments. We aimed to explore the effectiveness of repeated sessions of tDCS (eight sessions) targeting the C2 area and DLPFC in reducing fibromyalgia symptoms, more specifically pain and fatigue. Forty-two fibromyalgia patients received either C2 tDCS, DLPFC tDCS or sham procedure (15 C2 tDCS-11 DLPFC tDCS-16 sham). All groups were treated with eight sessions (two times a week for 4 weeks). Our results show that repeated sessions of C2 tDCS significantly improved pain, but not fatigue, in fibromyalgia patients, whereas repeated sessions of DLPFC tDCS significantly improved pain as well as fatigue. This study shows that eight sessions of tDCS targeting the DLPFC have a more general relief in fibromyalgia patients than when targeting the C2 area, suggesting that stimulating different targets with eight sessions of tDCS can lead to benefits on different symptom dimensions of fibromyalgia.

  9. Epigenetic regulation of the transcription factor Foxa2 directs differential elafin expression in melanocytes and melanoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Kyung Sook [Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Jo, Ji Yoon; Kim, Su Jin [Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Department of Functional Genomics, University of Science and Technology, Daejeon 305-333 (Korea, Republic of); Lee, Yangsoon [Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Bae, Jong Hwan [NeoPharm Co. Ltd., Daejeon 305-510 (Korea, Republic of); Chung, Young-Hwa [Department of Cogno-Mechatronics Engineering, BK21 Nanofusion Technology Team, Pusan National University, Busan 609-736 (Korea, Republic of); Koh, Sang Seok, E-mail: sskoh@kribb.re.kr [Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Department of Functional Genomics, University of Science and Technology, Daejeon 305-333 (Korea, Republic of)

    2011-04-29

    Highlights: {yields} Elafin expression is epigenetically silenced in human melanoma cells. {yields} Foxa2 expression in melanoma cells is silenced by promoter hypermethylation. {yields} Foxa2 directs activation of the elafin promoter in vivo. {yields} Foxa2 expression induces apoptosis of melanoma cells via elafin re-expression. -- Abstract: Elafin, a serine protease inhibitor, induces the intrinsic apoptotic pathway in human melanoma cells, where its expression is transcriptionally silenced. However, it remains unknown how the elafin gene is repressed in melanoma cells. We here demonstrate that elafin expression is modulated via epigenetically regulated expression of the transcription factor Foxa2. Treatment of melanoma cells with a DNA methyltransferase inhibitor induced elafin expression, which was specifically responsible for reduced proliferation and increased apoptosis. Suppression of Foxa2 transcription, mediated by DNA hypermethylation in its promoter region, was released in melanoma cells upon treatment with the demethylating agent. Luciferase reporter assays indicated that the Foxa2 binding site in the elafin promoter was critical for the activation of the promoter. Chromatin immunoprecipitation assays further showed that Foxa2 bound to the elafin promoter in vivo. Analyses of melanoma cells with varied levels of Foxa2 revealed a correlated expression between Foxa2 and elafin and the ability of Foxa2 to induce apoptosis. Our results collectively suggest that, in melanoma cells, Foxa2 expression is silenced and therefore elafin is maintained unexpressed to facilitate cell proliferation in the disease melanoma.

  10. Differentiation of human-induced pluripotent stem cell under flow conditions to mature hepatocytes for liver tissue engineering

    DEFF Research Database (Denmark)

    Starokozhko, Viktoriia; Hemmingsen, Mette; Larsen, Layla

    2018-01-01

    and to perform functional comparisons with fresh human precision-cut liver slices (hPCLS), an excellent benchmark for the human liver in vivo. The majority of the mRNA expression of CYP isoenzymes and transporters and the tested CYP activities, Phase II metabolism, and albumin, urea, and bile acid synthesis...... in the hiPSC-derived cells reached values that overlap those of hPCLS, which indicates a higher degree of hepatic differentiation than observed until now. Differentiation under flow compared with static conditions had a strong inducing effect on Phase II metabolism and suppressed AFP expression but resulted...... in slightly lower activity of some of the Phase I metabolism enzymes. Gene expression data indicate that hiPSCs differentiated into both hepatic and biliary directions. In conclusion, the hiPSC differentiated under flow conditions towards hepatocytes express a wide spectrum of liver functions at levels...

  11. Transcranial direct current stimulation facilitates cognitive multi-task performance differentially depending on anode location and subtask.

    Directory of Open Access Journals (Sweden)

    Melissa eScheldrup

    2014-09-01

    Full Text Available There is a need to facilitate acquisition of real world cognitive multi-tasks that require long periods of training (e.g., air traffic control, intelligence analysis, medicine. Non-invasive brain stimulation – specifically transcranial Direct Current Stimulation (tDCS – has promise as a method to speed multi-task training. We hypothesized that during acquisition of the complex multi-task Space Fortress, subtasks that require focused attention on ship control would benefit from tDCS aimed at the dorsal attention network while subtasks that require redirection of attention would benefit from tDCS aimed at the right hemisphere ventral attention network. We compared effects of 30 min prefrontal and parietal stimulation to right and left hemispheres on subtask performance during the first 45 min of training. The strongest effects both overall and for ship flying (control and velocity subtasks were seen with a right parietal (C4 to left shoulder montage, shown by modeling to induce an electric field that includes nodes in both dorsal and ventral attention networks. This is consistent with the re-orienting hypothesis that the ventral attention network is activated along with the dorsal attention network if a new, task-relevant event occurs while visuospatial attention is focused (Corbetta et al., 2008. No effects were seen with anodes over sites that stimulated only dorsal (C3 or only ventral (F10 attention networks. The speed subtask (update memory for symbols benefited from an F9 anode over left prefrontal cortex. These results argue for development of tDCS as a training aid in real world settings where multi-tasking is critical.

  12. Transcranial direct current stimulation facilitates cognitive multi-task performance differentially depending on anode location and subtask.

    Science.gov (United States)

    Scheldrup, Melissa; Greenwood, Pamela M; McKendrick, Ryan; Strohl, Jon; Bikson, Marom; Alam, Mahtab; McKinley, R Andy; Parasuraman, Raja

    2014-01-01

    There is a need to facilitate acquisition of real world cognitive multi-tasks that require long periods of training (e.g., air traffic control, intelligence analysis, medicine). Non-invasive brain stimulation-specifically transcranial Direct Current Stimulation (tDCS)-has promise as a method to speed multi-task training. We hypothesized that during acquisition of the complex multi-task Space Fortress, subtasks that require focused attention on ship control would benefit from tDCS aimed at the dorsal attention network while subtasks that require redirection of attention would benefit from tDCS aimed at the right hemisphere ventral attention network. We compared effects of 30 min prefrontal and parietal stimulation to right and left hemispheres on subtask performance during the first 45 min of training. The strongest effects both overall and for ship flying (control and velocity subtasks) were seen with a right parietal (C4, reference to left shoulder) montage, shown by modeling to induce an electric field that includes nodes in both dorsal and ventral attention networks. This is consistent with the re-orienting hypothesis that the ventral attention network is activated along with the dorsal attention network if a new, task-relevant event occurs while visuospatial attention is focused (Corbetta et al., 2008). No effects were seen with anodes over sites that stimulated only dorsal (C3) or only ventral (F10) attention networks. The speed subtask (update memory for symbols) benefited from an F9 anode over left prefrontal cortex. These results argue for development of tDCS as a training aid in real world settings where multi-tasking is critical.

  13. Imaging of hepatic steatosis and fatty sparing

    Energy Technology Data Exchange (ETDEWEB)

    Karcaaltincaba, Musturay [Department of Radiology, Hacettepe University School of Medicine, Ankara 06100 (Turkey)]. E-mail: musturayk@yahoo.com; Akhan, Okan [Department of Radiology, Hacettepe University School of Medicine, Ankara 06100 (Turkey)

    2007-01-15

    Radiology has gained importance in the non-invasive diagnosis of hepatic steatosis. Ultrasonography is usually the first imaging modality for the evaluation of hepatic steatosis. Unenhanced CT with or without dual kVp measurement and MRI with in and out of phase sequence can allow objective evaluation of hepatic steatosis. However, none of the imaging modalities can differentiate non-alcoholic steatohepatitis/fatty liver disease from simple steatosis. Evaluation of hepatic steatosis is important in donor evaluation before orthotopic liver transplantation and hepatic surgery. Recently, one-stop shop evaluation of potential liver donors has become possible by CT and MRI integrating vascular, parenchymal, volume and steatosis evaluation. Moreover hepatic steatosis (diffuse, multinodular, focal, subcortical, perilesional, intralesional, periportal and perivenular), hypersteatosis and sparing (geographic, nodular and perilesional or peritumoral) can cause diagnostic problems as a pseudotumor particularly in the evaluation of oncology patients. Liver MRI is used as a problem-solving tool in these patients. In this review, we discuss the current role of radiology in diagnosing, quantifying hepatic steatosis and solutions for diagnostic problems associated with fatty infiltration and sparing.

  14. Imaging of hepatic steatosis and fatty sparing

    International Nuclear Information System (INIS)

    Karcaaltincaba, Musturay; Akhan, Okan

    2007-01-01

    Radiology has gained importance in the non-invasive diagnosis of hepatic steatosis. Ultrasonography is usually the first imaging modality for the evaluation of hepatic steatosis. Unenhanced CT with or without dual kVp measurement and MRI with in and out of phase sequence can allow objective evaluation of hepatic steatosis. However, none of the imaging modalities can differentiate non-alcoholic steatohepatitis/fatty liver disease from simple steatosis. Evaluation of hepatic steatosis is important in donor evaluation before orthotopic liver transplantation and hepatic surgery. Recently, one-stop shop evaluation of potential liver donors has become possible by CT and MRI integrating vascular, parenchymal, volume and steatosis evaluation. Moreover hepatic steatosis (diffuse, multinodular, focal, subcortical, perilesional, intralesional, periportal and perivenular), hypersteatosis and sparing (geographic, nodular and perilesional or peritumoral) can cause diagnostic problems as a pseudotumor particularly in the evaluation of oncology patients. Liver MRI is used as a problem-solving tool in these patients. In this review, we discuss the current role of radiology in diagnosing, quantifying hepatic steatosis and solutions for diagnostic problems associated with fatty infiltration and sparing

  15. The role of MR imaging in detection of hepatic iron overload in patients with cirrhosis of different origins.

    Science.gov (United States)

    Szurowska, Edyta; Sikorska, Katarzyna; Izycka-Swieszewska, E; Nowicki, Tomasz; Romanowski, Tomasz; Bielawski, Krzysztof P; Studniarek, Michał

    2010-01-27

    There are many pathological conditions with hepatic iron overload. Classical definite diagnostic methods of these disorders are invasive and based on a direct tissue biopsy material. For the last years the role of MR imaging in liver diagnostics has been increasing. MRI shows changes of liver intensity in patients with hepatic iron overload. Changes in MR signal are an indirect consequence of change of relaxation times T2 and T2*, that can be directly measured. The purpose of the study was to evaluate usefulness of MR imaging in the detection of hepatic iron overload in patients with cirrhosis of different origins. MR imaging at 1.5T was prospectively performed in 44 patients with liver cirrhosis who had undergone liver biopsy with histopathological assessment of hepatic iron deposits. In all patients the following sequences were used: SE, Express, GRE in T2 and T1-weighted images. Signal intensity (SI) was measured on images obtained with each T2 weighted sequence by means of regions of interest, placed in the liver and paraspinal muscles. The correlation between iron overload, histopathological score, serum ferritin and SI ratio was analyzed. In 20 patients with iron overload confirmed by the biopsy, the liver parenchyma demonstrated lower signal intensity than that of paraspinal muscles. This effect was visible only in 8 patients with hepatic iron overload in Express T2-weighted images. Higher signal intensity of liver than that of skeletal muscles on GRE - T2 weighted images was noted in 24 patients with cirrhosis and without elevated hepatic iron concentration. We observed a correlation between low and high iron concentration and liver to muscle SI ratio. MR imaging is a useful and fast noninvasive diagnostic tool for the detection of liver iron overload in patients with cirrhosis of different origins.Liver to muscle SI ratio in GRE-T2-weighted sequence facilitates to differentiate patients with low and high degree of hepatic iron overload, which correlates

  16. SEIR model simulation for Hepatitis B

    Science.gov (United States)

    Side, Syafruddin; Irwan, Mulbar, Usman; Sanusi, Wahidah

    2017-09-01

    Mathematical modelling and simulation for Hepatitis B discuss in this paper. Population devided by four variables, namely: Susceptible, Exposed, Infected and Recovered (SEIR). Several factors affect the population in this model is vaccination, immigration and emigration that occurred in the population. SEIR Model obtained Ordinary Differential Equation (ODE) non-linear System 4-D which then reduces to 3-D. SEIR model simulation undertaken to predict the number of Hepatitis B cases. The results of the simulation indicates the number of Hepatitis B cases will increase and then decrease for several months. The result of simulation using the number of case in Makassar also found the basic reproduction number less than one, that means, Makassar city is not an endemic area of Hepatitis B.

  17. Isolated hepatic actinomycosis: a case report

    Directory of Open Access Journals (Sweden)

    Shehab Thomas M

    2010-02-01

    Full Text Available Abstract Introduction Actinomyces are slow growing, non-spore forming, gram-positive, branching bacilli that thrive in anaerobic and microareophilic conditions. Actinomyces are more commonly associated with oral and cervicofacial infections. Hepatic involvement in infections of the abdomen (known as isolated hepatic actinomycosis is rare, accounting for only 5% of all cases of actinomycosis. Case presentation We present the case of a 75-year-old Caucasian woman with a 3-month history of night sweats, fever, chills, abdominal bloating, anorexia, weight-loss, and early satiety. The patient was found to have isolated hepatic actinomycosis infection after undergoing a laparotomy with a biopsy of the liver. The patient has now recovered. Conclusion Isolated hepatic actinomycosis is a rare and often overlooked etiology for a liver mass. Given its subacute presentation and nondescript symptomatology, physicians should be aware of this differential and the potential pitfalls in diagnosis and management.

  18. "Hepatitis" - Prevention and management in dental practice.

    Science.gov (United States)

    Dahiya, Parveen; Kamal, Reet; Sharma, Varun; Kaur, Saravpreet

    2015-01-01

    Today, viral hepatitis has become a silent epidemic worldwide. It is the major cause of liver cirrhosis and liver carcinoma. In a dental office, infections can be expedited through several routes, including direct or indirect contact with blood, oral fluids, droplet splatter, aerosols, etc. The aim of the present review is to increase the awareness among dental practitioners, so as to reduce the burden of hepatitis in their community. Electronic databases like PubMed, Medline, ProQuest, etc. were searched using the keywords hepatitis, dentist, liver disease, and infection control. Manual search of various journals and books was also carried out. Only highly relevant articles from English literature were considered for the present review. The results revealed that the dentists were among the high-risk groups for hepatitis, and they have little information on the factors associated with adherence to hepatitis B vaccination. A dentist can play a major role in the prevention of hepatitis by considering each and every patient as a potential carrier of hepatitis. Proper infection control, sterilization, and prophylactic vaccination protocols should be followed in order to reduce the risk of hepatitis.

  19. Permanent magnetic field, direct electric field, and infrared to reduce blood glucose level and hepatic function in mus musculus with diabetic mellitus

    Science.gov (United States)

    Suhariningsih; Basuki Notobroto, Hari; Winarni, Dwi; Achmad Hussein, Saikhu; Anggono Prijo, Tri

    2017-05-01

    Blood contains several electrolytes with positive (cation) and negative (anion) ion load. Both electrolytes deliver impulse synergistically adjusting body needs. Those electrolytes give specific effect to external disturbance such as electric, magnetic, even infrared field. A study has been conducted to reduce blood glucose level and liver function, in type 2 Diabetes Mellitus patients, using Biophysics concept which uses combination therapy of permanent magnetic field, electric field, and infrared. This study used 48 healthy mice (mus musculus), male, age 3-4 weeks, with approximately 25-30 g in weight. Mice was fed with lard as high fat diet orally, before Streptozotocin (STZ) induction become diabetic mice. Therapy was conducted by putting mice in a chamber that emits the combination of permanent magnetic field, electric field, and infrared, every day for 1 hour for 28 days. There were 4 combinations of therapy/treatment, namely: (1) permanent magnetic field, direct electric field, and infrared; (2) permanent magnetic field, direct electric field, without infrared; (3) permanent magnetic field, alternating electric field, and infrared; and (4) permanent magnetic field, alternating electric field, without infrared. The results of therapy show that every combination is able to reduce blood glucose level, AST, and ALT. However, the best result is by using combination of permanent magnetic field, direct electric field, and infrared.

  20. Permanent magnetic field, direct electric field, and infrared to reduce blood glucose level and hepatic function in mus musculus with diabetic mellitus

    International Nuclear Information System (INIS)

    Suhariningsih; Prijo, Tri Anggono; Notobroto, Hari Basuki; Winarni, Dwi; Hussein, Saikhu Achmad

    2017-01-01

    Blood contains several electrolytes with positive (cation) and negative (anion) ion load. Both electrolytes deliver impulse synergistically adjusting body needs. Those electrolytes give specific effect to external disturbance such as electric, magnetic, even infrared field. A study has been conducted to reduce blood glucose level and liver function, in type 2 Diabetes Mellitus patients, using Biophysics concept which uses combination therapy of permanent magnetic field, electric field, and infrared. This study used 48 healthy mice ( mus musculus ), male, age 3-4 weeks, with approximately 25-30 g in weight. Mice was fed with lard as high fat diet orally, before Streptozotocin (STZ) induction become diabetic mice. Therapy was conducted by putting mice in a chamber that emits the combination of permanent magnetic field, electric field, and infrared, every day for 1 hour for 28 days. There were 4 combinations of therapy/treatment, namely: (1) permanent magnetic field, direct electric field, and infrared; (2) permanent magnetic field, direct electric field, without infrared; (3) permanent magnetic field, alternating electric field, and infrared; and (4) permanent magnetic field, alternating electric field, without infrared. The results of therapy show that every combination is able to reduce blood glucose level, AST, and ALT. However, the best result is by using combination of permanent magnetic field, direct electric field, and infrared. (paper)

  1. Rapid and efficient CRISPR/Cas9 gene inactivation in human neurons during human pluripotent stem cell differentiation and direct reprogramming.

    Science.gov (United States)

    Rubio, Alicia; Luoni, Mirko; Giannelli, Serena G; Radice, Isabella; Iannielli, Angelo; Cancellieri, Cinzia; Di Berardino, Claudia; Regalia, Giulia; Lazzari, Giovanna; Menegon, Andrea; Taverna, Stefano; Broccoli, Vania

    2016-11-18

    The CRISPR/Cas9 system is a rapid and customizable tool for gene editing in mammalian cells. In particular, this approach has widely opened new opportunities for genetic studies in neurological disease. Human neurons can be differentiated in vitro from hPSC (human Pluripotent Stem Cells), hNPCs (human Neural Precursor Cells) or even directly reprogrammed from fibroblasts. Here, we described a new platform which enables, rapid and efficient CRISPR/Cas9-mediated genome targeting simultaneously with three different paradigms for in vitro generation of neurons. This system was employed to inactivate two genes associated with neurological disorder (TSC2 and KCNQ2) and achieved up to 85% efficiency of gene targeting in the differentiated cells. In particular, we devised a protocol that, combining the expression of the CRISPR components with neurogenic factors, generated functional human neurons highly enriched for the desired genome modification in only 5 weeks. This new approach is easy, fast and that does not require the generation of stable isogenic clones, practice that is time consuming and for some genes not feasible.

  2. A Comparison of Tissue Spray and Lipid Extract Direct Injection Electrospray Ionization Mass Spectrometry for the Differentiation of Eutopic and Ectopic Endometrial Tissues

    Science.gov (United States)

    Chagovets, Vitaliy; Wang, Zhihao; Kononikhin, Alexey; Starodubtseva, Natalia; Borisova, Anna; Salimova, Dinara; Popov, Igor; Kozachenko, Andrey; Chingin, Konstantin; Chen, Huanwen; Frankevich, Vladimir; Adamyan, Leila; Sukhikh, Gennady

    2018-02-01

    Recent research revealed that tissue spray mass spectrometry enables rapid molecular profiling of biological tissues, which is of great importance for the search of disease biomarkers as well as for online surgery control. However, the payback for the high speed of analysis in tissue spray analysis is the generally lower chemical sensitivity compared with the traditional approach based on the offline chemical extraction and electrospray ionization mass spectrometry detection. In this study, high resolution mass spectrometry analysis of endometrium tissues of different localizations obtained using direct tissue spray mass spectrometry in positive ion mode is compared with the results of electrospray ionization analysis of lipid extracts. Identified features in both cases belong to three lipid classes: phosphatidylcholines, phosphoethanolamines, and sphingomyelins. Lipids coverage is validated by hydrophilic interaction liquid chromatography with mass spectrometry of lipid extracts. Multivariate analysis of data from both methods reveals satisfactory differentiation of eutopic and ectopic endometrium tissues. Overall, our results indicate that the chemical information provided by tissue spray ionization is sufficient to allow differentiation of endometrial tissues by localization with similar reliability but higher speed than in the traditional approach relying on offline extraction.

  3. A fast direct method for block triangular Toeplitz-like with tri-diagonal block systems from time-fractional partial differential equations

    Science.gov (United States)

    Ke, Rihuan; Ng, Michael K.; Sun, Hai-Wei

    2015-12-01

    In this paper, we study the block lower triangular Toeplitz-like with tri-diagonal blocks system which arises from the time-fractional partial differential equation. Existing fast numerical solver (e.g., fast approximate inversion method) cannot handle such linear system as the main diagonal blocks are different. The main contribution of this paper is to propose a fast direct method for solving this linear system, and to illustrate that the proposed method is much faster than the classical block forward substitution method for solving this linear system. Our idea is based on the divide-and-conquer strategy and together with the fast Fourier transforms for calculating Toeplitz matrix-vector multiplication. The complexity needs O (MNlog2 ⁡ M) arithmetic operations, where M is the number of blocks (the number of time steps) in the system and N is the size (number of spatial grid points) of each block. Numerical examples from the finite difference discretization of time-fractional partial differential equations are also given to demonstrate the efficiency of the proposed method.

  4. Vasa promotes Drosophila germline stem cell differentiation by activating mei-P26 translation by directly interacting with a (U)-rich motif in its 3' UTR.

    Science.gov (United States)

    Liu, Niankun; Han, Hong; Lasko, Paul

    2009-12-01

    Vasa (Vas) is a DEAD-box RNA-binding protein required in Drosophila at several steps of oogenesis and for primordial germ cell (PGC) specification. Vas associates with eukaryotic initiation factor 5B (eIF5B), and this interaction has been implicated in translational activation of gurken mRNA in the oocyte. Vas is expressed in all ovarian germline cells, and aspects of the vas-null phenotype suggest a function in regulating the balance between germline stem cells (GSCs) and their fate-restricted descendants. We used a biochemical approach to recover Vas-associated mRNAs and obtained mei-P26, whose product represses microRNA activity and promotes GSC differentiation. We found that vas and mei-P26 mutants interact, and that mei-P26 translation is substantially reduced in vas mutant cells. In vitro, Vas protein bound specifically to a (U)-rich motif in the mei-P26 3' untranslated region (UTR), and Vas-dependent regulation of GFP-mei-P26 transgenes in vivo was dependent on the same (U)-rich 3' UTR domain. The ability of Vas to activate mei-P26 expression in vivo was abrogated by a mutation that greatly reduces its interaction with eIF5B. Taken together, our data support the conclusion that Vas promotes germ cell differentiation by directly activating mei-P26 translation in early-stage committed cells.

  5. [Differential expression of IGF-I and its mRNA in mandibular condylar cartilage of rat--direct evidence for servosystem theory of facial growth].

    Science.gov (United States)

    Zhou, Z; Luo, S

    1998-05-01

    It was studied the expression of IGF-I and its mRNA in the condylar cartilage of 10 7-week-old SD male rats by using in situ hybridization and immunohisto-chemistry technique. The results showed both IGF-I and its gene expressed in growing rat condyle. IGF-I peptide was abundant in germinal zone, and positive reaction of its mRNA was strongest in transitional and maturational zones. These indicate that condylar cartilage has the capability of local production and secretion of IGF-I, mediating the command effect of STH, and differential expression of IGF-I and its mRNA might establish the local feedback loop, which supply a direct evidence for servosystem theory of facial growth.

  6. A Case of Typhoid Fever with Hepatic Granulomas and Enteritis

    Directory of Open Access Journals (Sweden)

    Shraddha Narechania

    2015-01-01

    Full Text Available The common histopathologic hepatic manifestations in patients infected with Salmonella include cloudy swelling and balloon degeneration with vacuolation of the hepatocytes and steatosis. Hepatic granulomas are a very rare finding, so far reported in very few cases. We report a 64-year-old patient with Salmonella enteritis who was found to have multiple 1.4 to 1.6 cm hypoechoic liver masses on ultrasound of the abdomen which on biopsy revealed hepatic granulomas. This case highlights the importance of keeping the differential diagnosis of Salmonella typhi (S. typhi in mind in a patient with hepatic granulomas.

  7. The Differential Effect of Two Types of Direct Written Corrective Feedback on Noticing and Uptake: Reformulation vs. Error Correction

    Directory of Open Access Journals (Sweden)

    Rosa M. Manchón

    2010-06-01

    Full Text Available Framed in a cognitively-oriented strand of research on corrective feedback (CF in SLA, the controlled three- stage (composition/comparison-noticing/revision study reported in this paper investigated the effects of two forms of direct CF (error correction and reformulation on noticing and uptake, as evidenced in the written output produced by a group of 8 secondary school EFL learners. Noticing was operationalized as the amount of corrections noticed in the comparison stage of the writing task, whereas uptake was operationally defined as the type and amount of accurate revisions incorporated in the participants’ revised versions of their original texts. Results support previous research findings on the positive effects of written CF on noticing and uptake, with a clear advantage of error correction over reformulation as far as uptake was concerned. Data also point to the existence of individual differences in the way EFL learners process and make use of CF in their writing. These findings are discussed from the perspective of the light they shed on the learning potential of CF in instructed SLA, and suggestions for future research are put forward.Enmarcado en la investigación de orden cognitivo sobre la corrección (“corrective feedback”, en este trabajo se investigó la incidencia de dos tipos de corrección escrita (corrección de errores y reformulación en los procesos de detección (noticing e incorporación (“uptake”. Ocho alumnos de inglés de Educción Secundaria participaron en un experimento que constó de tres etapas: redacción, comparación-detección y revisión. La detección se definió operacionalmente en términos del número de correcciones registradas por los alumnos durante la etapa de detección-comparación, mientras que la operacionalización del proceso de incorporación fue el tipo y cantidad de revisiones llevadas a cabo en la última etapa del experimento. Nuestros resultados confirman los hallazgos de la

  8. Diabetes and Hepatitis B Vaccination

    Science.gov (United States)

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

  9. Hepatitis Information for the Public

    Science.gov (United States)

    ... Hepatitis Contact Us Anonymous Feedback Quick Links to Hepatitis … A | B | C | D | E Viral Hepatitis Home ... Local Partners & Grantees Policy and Programs Resource Center Hepatitis Information for the Public Recommend on Facebook Tweet ...

  10. Immunoglobulins for preventing hepatitis A

    DEFF Research Database (Denmark)

    Liu, Jian Ping; Nikolova, Dimitrinka; Fei, Yutong

    2009-01-01

    Hepatitis A (infectious hepatitis) is a common epidemic disease. Immunoglobulins for passive immunisation are used as prevention.......Hepatitis A (infectious hepatitis) is a common epidemic disease. Immunoglobulins for passive immunisation are used as prevention....

  11. 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...

  12. Axitinib for preoperative downstaging of renal cell carcinoma with sarcomatoid differentiation and direct invasion of the duodenum and inferior vena cava: a case report

    Directory of Open Access Journals (Sweden)

    Yuki H

    2014-02-01

    Full Text Available Hideo Yuki,1,* Takao Kamai,1,* Keiichi Kubota,2 Hideyuki Abe,1 Daisaku Nishihara,1 Tomoya Mizuno,1 Akinori Masuda,1 Hironori Betsunoh,1 Masahiro Yashi,1 Yoshitatsu Fukabori,1 Ken-Ichiro Yoshida1 1Department of Urology, 2Department of Gastroenterological Surgery, Dokkyo Medical University, Mibu, Tochigi, Japan *These authors contributed equally to this manuscript Background: Renal cell carcinoma (RCC with sarcomatoid differentiation is invasive, refractory to treatment, and has a higher mortality. Therefore, systemic therapy is still challenging, and the curative resection of localized or locally advanced RCC with sarcomatoid differentiation is very important. Axitinib is a potent and selective second-generation vascular endothelial growth factor receptor tyrosine kinase inhibitor with improved safety and tolerability. Axitinib is generally recommended as second-line therapy for advanced RCC because the phase III axitinib versus sorafenib in advanced RCC (AXIS trial demonstrated that it achieved longer progression-free survival than sorafenib in patients with metastatic RCC after failure of an approved first-line regimen. Methods: We present a 73-year-old man who had a large (13 cm in diameter right RCC with sarcomatoid differentiation that directly invaded the duodenum and inferior vena cava. The patient presented with gastrointestinal bleeding, was unable to eat solid food, and had become emaciated. Thus, his classification was poor risk with anemia, hypercalcemia, and poor performance status, according to the Memorial Sloan-Kettering Cancer Center criteria. He seemed unlikely to survive if radical nephrectomy, cavotomy with thrombectomy, and pancreatoduodenectomy were performed. To reduce the tumor burden and potential operative complications, we administered axitinib as first-line neoadjuvant therapy. Results: Six weeks of treatment reduced the tumor burden without causing severe toxicities. Subsequently, radical right nephrectomy, cavotomy

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

    Science.gov (United States)

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

    2015-08-28

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

  14. Effects of glucose ingestion on hepatic hemodynamics in patients with liver disease by per-rectal portal scintigraphy using 99mTcO4- (direct intramural administration of radioisotope method)

    International Nuclear Information System (INIS)

    Tetsuka, Isando; Ohe, Takashi; Harada, Takashi

    1992-01-01

    Effect of glucose (225 ml, 300 kcal) ingestion on hepatic hemodynamics was studied in ten patients with liver cirrhosis and eight patients with non cirrhotic liver disease by per-rectal portal scintigraphy using 99m TcO 4 - (direct intramural administration of radioisotope method). Initial portal blood flow index (IP) and collateral index (CI) were calculated from the time activity curve of heart and liver. The value of IP was not significantly changed between before and after glucose ingestion in cases of liver cirrhosis (before: 0.0160±0.0016, after: 0.0204±0.0106). In cases of non cirrhotic liver disease, the value of IP was significantly increased after glucose ingestion (before: 0.0381±0.0145, after: 0.0544±0.0194, p<0.02). These findings suggested increase in portal blood flow via inferior mesenteric vein to the cardiac blood flow. The value of CI before glucose ingestion was significantly increased in cases of liver cirrhosis (0.751±0.156) compared with that in cases of non cirrhotic liver disease (0.517±0.122), but no significant difference in values after glucose ingestion was found between these two groups. (author)

  15. Proteomic analysis of stipe explants reveals differentially</