DNA Vaccination of the American Crow (Corvus brachyrhynchos) Provides Partial Protection Against Lethal Challenge with West Nile Virus

DTIC Science & Technology

2007-01-01

mortality but did not provide sterile immunity. RESUMEN. La vacunación del cuervo Americano (Corvus brachyrhynchos) con vacuna de ADN proporciona...casi 100% fatal en el cuervo Americano (Corvus brachyrhynchos). Evaluamos cuatro formulaciones de vacunas en cuervos Americanos, incluyendo una vacuna de...ADN, una vacuna de ADN con adyuvante, ambas aplicadas por la vı́a intramuscular, una vacuna de ADN microencapsulada aplicada por la vı́a oral, y una

Anti-hepatitis B virus activity of Boehmeria nivea leaf extracts in human HepG2.2.15 cells

PubMed Central

WEI, JINGCHEN; LIN, LIANKU; SU, XIAOJIAN; QIN, SHAOYAN; XU, QING; TANG, ZUNIAN; DENG, YAN; ZHOU, YUEHAN; HE, SONGQING

2014-01-01

Boehmeria nivea (Linn.) Gaudich of the Urticaceae family is a perennial ratoon herbal plant, the root of which is used in traditional Chinese medicine and possesses a variety of pharmacological properties. The 20% ethanol Boehmeria nivea root extract was shown to exert an anti-hepatitis B virus (HBV) effect in vitro and in vivo; however, whether the Boehmeria nivea leaf (BNL) extract possesses similar properties has not been determined. In this study, we aimed to investigate the anti-HBV effects of the BNL extract in HepG2.2.15 cells transfected with human HBV DNA. Our results demonstrated that the secretion of HBsAg and HBeAg was reduced in HepG2.2.15 cells treated with the BNL extract, without any recorded cytotoxic effects. In addition, the chloroform fraction (CF) and ethyl acetate fraction (EAF) of BNL were shown to be more potent compared to the other fractions: CF (100 mg/l) inhibited the secretion of HBsAg by 94.00±1.78% [inhibitory concentration 50 (IC50) = 20.92 mg/l] and that of HBeAg by 100.19±0.35% (IC50=19.67 mg/l) after 9 days of treatment. Similarly, EAF (200 mg/l) inhibited the secretion of HBsAg by 89.95±2.26% (IC50=39.90 mg/l) and that of HBeAg by 98.90±1.42% (IC50=36.45 mg/l). Furthermore, we observed that the content of HBV DNA in the medium secreted by the HepG2.2.15 cells was significantly decreased under CF (100 mg/l) or EAF (200 mg/l) treatment. Thus, we concluded that the BNL extracts exhibited anti-HBV activity, with CF and EAF being the most potent among the fractions. PMID:24649087

Anti-hepatitis B virus activity of Boehmeria nivea leaf extracts in human HepG2.2.15 cells.

PubMed

Wei, Jingchen; Lin, Lianku; Su, Xiaojian; Qin, Shaoyan; Xu, Qing; Tang, Zunian; Deng, Yan; Zhou, Yuehan; He, Songqing

2014-01-01

Boehmeria nivea (Linn.) Gaudich of the Urticaceae family is a perennial ratoon herbal plant, the root of which is used in traditional Chinese medicine and possesses a variety of pharmacological properties. The 20% ethanol Boehmeria nivea root extract was shown to exert an anti-hepatitis B virus (HBV) effect in vitro and in vivo ; however, whether the Boehmeria nivea leaf (BNL) extract possesses similar properties has not been determined. In this study, we aimed to investigate the anti-HBV effects of the BNL extract in HepG2.2.15 cells transfected with human HBV DNA. Our results demonstrated that the secretion of HBsAg and HBeAg was reduced in HepG2.2.15 cells treated with the BNL extract, without any recorded cytotoxic effects. In addition, the chloroform fraction (CF) and ethyl acetate fraction (EAF) of BNL were shown to be more potent compared to the other fractions: CF (100 mg/l) inhibited the secretion of HBsAg by 94.00±1.78% [inhibitory concentration 50 (IC 50 ) = 20.92 mg/l] and that of HBeAg by 100.19±0.35% (IC 50 =19.67 mg/l) after 9 days of treatment. Similarly, EAF (200 mg/l) inhibited the secretion of HBsAg by 89.95±2.26% (IC 50 =39.90 mg/l) and that of HBeAg by 98.90±1.42% (IC 50 =36.45 mg/l). Furthermore, we observed that the content of HBV DNA in the medium secreted by the HepG2.2.15 cells was significantly decreased under CF (100 mg/l) or EAF (200 mg/l) treatment. Thus, we concluded that the BNL extracts exhibited anti-HBV activity, with CF and EAF being the most potent among the fractions.

Effects of ketoconazole and rifampicin on the pharmacokinetics of GLS4, a novel anti-hepatitis B virus compound, in dogs

PubMed Central

Zhou, Xin; Gao, Zhi-wei; Meng, Jian; Chen, Xiao-yan; Zhong, Da-fang

2013-01-01

Aim: To investigate the metabolism of GLS4, a heteroaryldihydropyrimidine compound with anti-hepatitis B virus activity, in dog and human liver microsomes in vitro and evaluate the effects of ketoconazole (a potent CYP3A inhibitor) or rifampicin (a potent CYP3A inducer) on GLS4 pharmacokinetics in dogs. Methods: Dog and human liver microsomes and CYP3A4 were incubated with [14C]GLS4 for 15 min and then analyzed using a HPLC-dynamic online radio flow detection method. Two groups of beagle dogs were used for in vivo studies. Group A were orally administered a single dose of GLS4 (15 mg/kg) with or without ketoconazole pretreatment (100 mg/d for 8 consecutive days). Group B were orally administered a single dose of GLS4 (15 mg/kg) with or without rifampicin pretreatment (100 mg/d for 8 consecutive days). Plasma was sampled after GLS4 dosing. GLS4 concentrations were determined by HPLC-tandem mass spectrometry. Results: The metabolic profile of [14C]GLS4 in human and dog liver microsomes and CYP3A4 was similar. The major metabolites were morpholine N-dealkylated GLS4 and morpholine N,N-di-dealkylated GLS4. Pretreatment with ketoconazole or rifampicin significantly affected the plasma concentrations of GLS4 in dogs: ketoconazole increased the area under the concentration-time curve from 0 to infinity and peak concentration of GLS4 by 4.4 and 3.3 folds, respectively, whereas rifampicin decreased these parameters by 88.5% and 83.2%, respectively. Conclusion: GLS4 is a sensitive substrate of CYP3A. CYP3A inhibitors or inducers cause considerable change of GLS4 plasma concentrations in dogs, which should be considered in clinical practice. PMID:24056704

Effects of ketoconazole and rifampicin on the pharmacokinetics of GLS4, a novel anti-hepatitis B virus compound, in dogs.

PubMed

Zhou, Xin; Gao, Zhi-wei; Meng, Jian; Chen, Xiao-yan; Zhong, Da-fang

2013-11-01

To investigate the metabolism of GLS4, a heteroaryldihydropyrimidine compound with anti-hepatitis B virus activity, in dog and human liver microsomes in vitro and evaluate the effects of ketoconazole (a potent CYP3A inhibitor) or rifampicin (a potent CYP3A inducer) on GLS4 pharmacokinetics in dogs. Dog and human liver microsomes and CYP3A4 were incubated with [(14)C]GLS4 for 15 min and then analyzed using a HPLC-dynamic online radio flow detection method. Two groups of beagle dogs were used for in vivo studies. Group A were orally administered a single dose of GLS4 (15 mg/kg) with or without ketoconazole pretreatment (100 mg/d for 8 consecutive days). Group B were orally administered a single dose of GLS4 (15 mg/kg) with or without rifampicin pretreatment (100 mg/d for 8 consecutive days). Plasma was sampled after GLS4 dosing. GLS4 concentrations were determined by HPLC-tandem mass spectrometry. The metabolic profile of [(14)C]GLS4 in human and dog liver microsomes and CYP3A4 was similar. The major metabolites were morpholine N-dealkylated GLS4 and morpholine N,N-di-dealkylated GLS4. Pretreatment with ketoconazole or rifampicin significantly affected the plasma concentrations of GLS4 in dogs: ketoconazole increased the area under the concentration-time curve from 0 to infinity and peak concentration of GLS4 by 4.4 and 3.3 folds, respectively, whereas rifampicin decreased these parameters by 88.5% and 83.2%, respectively. GLS4 is a sensitive substrate of CYP3A. CYP3A inhibitors or inducers cause considerable change of GLS4 plasma concentrations in dogs, which should be considered in clinical practice.

Changes in the seroprevalence of IgG anti-hepatitis A virus between 2001 and 2013: experience at a single center in Korea

PubMed Central

Chung, Sung Jun; Kim, Sun Min; Roh, Min; Yu, Mi Yeon; Lee, Jung Hoon; Oh, ChangKyo; Lee, Eun Young; Lee, Seung; Jeon, Yong Cheol; Yoo, Kyo-Sang; Sohn, Joo Hyun

2014-01-01

Background/Aims The incidence of symptomatic hepatitis A reportedly increased among 20- to 40-year-old Korean during the late 2000s. Vaccination against hepatitis A was commenced in the late 1990s and was extended to children aged <10 years. In the present study we analyzed the changes in the seroprevalence of IgG anti-hepatitis A virus (HAV) over the past 13 years. Methods Overall, 4903 subjects who visited our hospital between January 2001 and December 2013 were studied. The seroprevalence of IgG anti-HAV was analyzed according to age and sex. In addition, the seroprevalence of IgG anti-HAV was compared among 12 age groups and among the following time periods: early 2000s (2001-2003), mid-to-late 2000s (2006-2008), and early 2010s (2011-2013). The chi-square test for trend was used for statistical analysis. Results The seroprevalence of IgG anti-HAV did not differ significantly between the sexes. Furthermore, compared to the seroprevalence of IgG anti-HAV in the early 2000s and mid-to-late 2000s, that in the early 2010s was markedly increased among individuals aged 1-14 years and decreased among those aged 25-44 years (P<0.01). We also found that the seroprevalence of IgG anti-HAV in individuals aged 25-44 years in the early 2010s was lower than that in the early 2000s and mid-to-late 2000s. Conclusions The number of symptomatic HAV infection cases in Korea is decreasing, but the seroprevalence of IgG anti-HAV is low in the active population. PMID:25032182

The S-acyl-2-thioethyl pronucleotide approach applied to acyclovir: part I. Synthesis and in vitro anti-hepatitis B virus activity of bis(S-acyl-2-thioethyl)phosphotriester derivatives of acyclovir.

PubMed

Périgaud, C; Gosselin, G; Girardet, J L; Korba, B E; Imbach, J L

1999-01-01

The synthesis and in vitro anti-hepatitis B virus (HBV) activity of two mononucleoside phosphotriester derivatives of acyclovir incorporating S-acyl-2-thioethyl (SATE) groups are reported. In contrast to the parent nucleoside, the described phosphotriesters emerged as potent and selective inhibitors of HBV replication in HepG2.2.15 cells. This result can be attributed to the unique cellular metabolism of the SATE pronucleotides giving rise to the delivery to acyclovir 5'-monophosphate inside the infected cells. Moreover, the in vitro anti-HBV activities of one of these bis(SATE)phosphotriesters and of (-)-beta-L-2',3'-dideoxy-3'-thiacytidine (lamivudine, 3TC) were compared alone and in combination. Analysis of the combination data indicates that 3TC and the studied SATE pronucleotide of acyclovir exhibited strong synergistic interactions. The present study provides an example where the use of a pronucleotide approach extends the antiviral spectrum of a nucleoside analogue. Given the potency of SATE pronucleotides of acyclovir against HBV in HepG2.2.15 cells, further studies including animal experiments seem warranted to evaluate the potential of these compounds as anti-HBV agents.

[Comparative Study for Anti-Hepatitis B Surface Antigen Titers Based on Two Measurement Methods: Using Monoclonal Antibodies Isolated from Hepatitis B Vaccinated Recipients].

PubMed

Oone, Kumiko; Kani, Satomi; Oohashi, Minoru; Shinkai, Noboru; Inoue, Takako; Wakimoto, Yukio; Tanaka, Yasuhito

2015-08-01

As anti-hepatitis B surface antigen (anti-HBs) titers vary depending on the measurement methods, we compared two different methods to measure anti-HBs titers in sera and HBs monoclonal antibodies. The sera from 182 HB virus-resolved patients who were negative for HBsAg but positive for antiHB core protein (HBc) and/or anti-HBs were obtained. The measurement of anti-HBs was compared using either Lumipulse G1200 or Architect i2000SR. Six different monoclonal antibody (mAbs) clones isolated from healthy individuals inoculated with hepatitis B vaccine Bimmugen (genotype C) were used. A statistically significant correlation in anti-HBs titers was found between the two methods tested (Y = 0.951X + 100.7, R = 0.813, p < 0.001), although anti-HBs titers in 72 samples (39.6%) measured by Architect were less than 50% of that by Lumipulse and 12 (6.6%) were opposite results. Measuring 2 mAbs with HBV neutralizing activity, the titers of the 116 antibody (1.0 μg/mL) were comparable (689.3 mIU/mL by Lumipulse and 440.7 mIU/mL by Architect), whereas those of the 478 antibody (1.0 μg/mL) were much lower by Architect than by Lumipulse (42.6 vs. 818.6 mIU/mL, respectively). Of four other mAbs without HBV neutralizing activity, equal titers were observed for one; two mAbs had less anti-HB titers by Architect; and one was below the cut-off index (< 5 mIU/mL). Anti-HBs titers measured by Architect are likely to be lower than by Lumipulse, and the potential ability to detect the 478 antibody with neutralizing activity is low, indicating that Architect might underestimate anti-HBs titers. Future studies should standardize the anti-HBs titer measurement system.

Core promoter mutations 3 years after anti-hepatitis B e seroconversion in patients with chronic hepatitis B or hepatitis B and C infection and cancer remission.

PubMed

Zampino, Rosa; Marrone, Aldo; Karayiannis, Peter; Cirillo, Grazia; del Giudice, Emanuele Miraglia; Rania, Giovanni; Utili, Riccardo; Ruggiero, Giuseppe

2002-09-01

In this study, we aimed to evaluate the persistence of hepatitis B virus (HBV) DNA and the role of HBV core promoter and precore region mutations in 28 young cancer survivor patients with HBV or HBV and hepatitis C virus (HCV) infections, and persistently normal ALT levels, after spontaneous or interferon (IFN)-induced anti-hepatitis B e (HBe) seroconversion. Sera from 15 patients with HBV and 13 with dual HBV-HCV infection were analyzed for the presence of HBV-DNA and HCV-RNA by polymerase chain reaction 3 yr after anti-HBe seroconversion. A total of 21 patients had seroconverted spontaneously and seven did so after IFN treatment. The core promoter and the precore regions were amplified sequenced directly. Among patients with HBV infection, HBV-DNA was detected in five of nine (55%) with spontaneous anti-HBe and in all six treated patients (p = 0.092). In the coinfected patients, four had cleared both HBV-DNA and HCV-RNA, five were HBV-DNA negative/HCV-RNA positive and four had the reverse viral pattern. Among the 15 patients with persistence of HBV-DNA, a 7-base pair nucleotide deletion in the core promoter (1757-1763) was present in seven of 10 patients with spontaneous and in one of five patients with IFN-induced seroconversion (p = 0.033). The G1896A precore stop codon mutation was never observed. HBV-DNA levels were significantly lower in patients with the core promoter deletion (p = 0.011). The 7-base pair deletion generated a truncated X protein at amino-acid position 132. A core promoter deletion after anti-HBe seroconversion was associated with low HBV-DNA levels, probably because of downregulation of pregenomic RNA production and truncation of the X protein. HBV-DNA persistence was a frequent event, even in the absence of active liver disease.

General epidemiological parameters of viral hepatitis A, B, C, and E in six regions of China: a cross-sectional study in 2007.

PubMed

Lu, Jian; Zhou, Yongdong; Lin, Xiaojing; Jiang, Yongzhen; Tian, Ruiguang; Zhang, Yonghui; Wu, Jia; Zhang, Fengwei; Zhang, Yong; Wang, Yue; Bi, Shengli

2009-12-24

Viral hepatitis is a serious health burden worldwide. To date, few reports have addressed the prevalence of hepatitis A, B, C, and E in China. Therefore, the general epidemiological parameters of viral hepatitis remain unknown. In this cross-sectional study, we performed a serological prevalence analysis of viral hepatitis A, B, C, and E in 8,762 randomly selected Chinese subjects, which represented six areas of China. The overall prevalence of anti-Hepatitis C virus antibody (anti-HCV) was 0.58%, which was much lower than was estimated by WHO. The prevalences of Hepatitis B virus surface antigen (HBsAg), anti-Hepatitis B virus surface protein antibody (HBsAb), and anti-Hepatitis B virus core protein antibody (HBcAb) were 5.84%, 41.31%, and 35.92%, respectively, whereas in the group of subjects less than 5 years old, these prevalences were 1.16%, 46.77%, and 8.69% respectively, which suggests that the Hepatitis B virus (HBV)-carrier population is decreasing, and the nationwide HBV vaccine program has contributed to the lowered HBV prevalence in the younger generation in China. Meanwhile, a large deficit remains in coverage provided by the national HBV immune program. In addition, our data suggested the possibility that HBsAb may not last long enough to protect people from HBV infection throughout life. The overall prevalence of anti-Hepatitis A virus antibody (anti-HAV) and anti-Hepatitis E virus antibody (anti-HEV) were as high as 72.87% and 17.66%, respectively. The indices increased with age, which suggests that a large proportion of Chinese adults are protected by latent infection. Furthermore, the pattern of HEV infection was significantly different among ethnic groups in China. Our study provided much important information concerning hepatitis A, B, C, and E prevalence in China and will contribute to worldwide oversight of viral hepatitis.

Immunologic Control of Diarrheal Disease Due to Enterotoxigenic Escherichia coli

DTIC Science & Technology

1984-01-01

Classical Enteropathogenic (Serotyped) Escherichia coli Strains of Proven Pathogenicity. Infect. Immun. 38:798-801, 1982. 8. Levine, M.M. Vacunas Contra...Microbiol., 18:808-815, 1983. 8 15. Levine, M.M., Lanata, C. Progresos en Vacunas Contra Diarrea Bacteriana. Adelantos Microbiol. Enferm. Inf., 2:67-117

Hepatitis B virus DNA-positive, hepatitis B surface antigen-negative blood donations intercepted by anti-hepatitis B core antigen testing: the Canadian Blood Services experience.

PubMed

O'Brien, Sheila F; Fearon, Margaret A; Yi, Qi-Long; Fan, Wenli; Scalia, Vito; Muntz, Irene R; Vamvakas, Eleftherios C

2007-10-01

The benefit of introducing anti-hepatitis B core antigen (HBc) screening for intercepting potentially infectious donations missed by hepatitis B surface antigen (HBsAg) screening in Canada was studied. Anti-HBc testing of all donations was implemented in April 2005, along with antibody to hepatitis B surface antigen (anti-HBs) and hepatitis B virus (HBV) DNA supplemental testing of anti-HBc repeat-reactive, HBsAg-negative donations. The proportion of potentially infectious donations intercepted by anti-HBc over the initial 18 months of testing was calculated based on three assumptions relating infectivity of HBV DNA-positive units to anti-HBs levels. Lookback was conducted for all DNA-positive donations. Of 493,344 donors, 5,585 (1.13%) were repeat-reactive for the presence of anti-HBc, with 29 (0.52%) being HBV DNA-positive and HBsAg-negative. The proportion of potentially infectious donations intercepted by anti-HBc screening was 1 in 17,800 if all HBV DNA-positive donations were infectious, 1 in 26,900 if infectivity was limited to donations with an anti-HBs level of not more than 100 mIU per mL, and 1 in 69,300 if only donations with undetectable anti-HBs were infectious. For 279 components in the lookback study, no traced recipients were HBsAg-positive and 7 recipients were anti-HBc-reactive in association with 4 donors, 3 of whom had an anti-HBs level of more than 100 mIU per mL and 1 of whom had a level of 61 mIU per mL. Implementation of anti-HBc screening reduced the risk of transfusing potentially infectious units by at least as much as had been expected based on the literature. The lookback did not provide proof of transfusion transmission of HBV from HBV DNA-positive, anti-HBc-reactive, HBsAg-negative donors but it did not establish lack of transmission either.

Synthesis, spectroscopic characterization, theoretical study and anti-hepatic cancer activity study of 4-(1E,3Z,6E)-3-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-5-oxohepta-1,3,6-trien-1-yl)-2-methoxyphenyl 4-nitrobenzoate, a novel curcumin congener

NASA Astrophysics Data System (ADS)

Srivastava, Sangeeta; Gupta, Preeti; Singh, Ranvijay Pratap; Jafri, Asif; Arshad, M.; Banerjee, Monisha

2017-08-01

In the present work 4-(1E,3Z,6E)-3-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-5-oxohepta-1,3,6-trien-1-yl)-2-methoxyphenyl 4-nitrobenzoate (2), a novel curcumin ester was synthesized. The molecular structure and spectroscopic analysis were performed using experimental techniques like FT-IR, 1H,13C NMR, mass and UV-visible as well as theoretical calculations. The theoretical calculations were done by DFT level of theory using B3LYP/6-31G (d,p) basis set. The vibrational wavenumbers were calculated using DFT method and assigned with the help of potential energy distribution (PED). The electronic properties such as frontier orbitals and band gap energies have been calculated using time dependent density functional theory (TD-DFT). The strength and nature of weak intramolecular interactions have been studied by AIM approach. Global and local reactivity descriptors have been computed to predict reactivity and reactive sites in the molecule. First hyperpolarizability values have been calculated to describe the nonlinear optical (NLO) property of the synthesized compounds. Molecular electrostatic potential (MEP) analysis has also been carried out. The anti-hepatic cancer activity of compound 2 was also carried out.

Antibody persistence and immune memory 4 years post-vaccination with combined hepatitis A and B vaccine in adults aged over 40 years.

PubMed

Chlibek, Roman; von Sonnenburg, Frank; Van Damme, Pierre; Smetana, Jan; Tichy, Petr; Gunapalaiah, Bhavyashree; Leyssen, Maarten; Jacquet, Jeanne-Marie

2011-01-01

Persistence of immune response was assessed in adults aged >40 years (N = 596) following primary vaccination with combined hepatitis A/B vaccine or concomitant monovalent hepatitis A and B vaccines. Anti-hepatitis A virus antibody responses persisted for at least 4 years regardless of the vaccine used, with anti-hepatitis B surface antibody responses higher and more sustained in subjects who received the combined hepatitis A/B vaccine. Response rates to an additional dose of the same vaccine(s) used for priming were high. © 2011 International Society of Travel Medicine.

Need for immunization against hepatotropic viruses in children with chronic liver disease.

PubMed

Srivastava, Anshu; Mathias, Amrita; Yachha, Surender Kumar; Agarwal, Jaya; Aggarwal, Rakesh

2014-09-01

Infection with hepatotropic viruses is a common cause of acute deterioration and adverse outcome in children with chronic liver disease (CLD). Such superimposed infections may be preventable through vaccination. The present study aimed to evaluate the exposure rates of hepatitis A, B, and E viruses in children with CLD and suggest an optimal vaccination strategy. Children with CLD were prospectively evaluated with a demographic, clinical, and investigative proforma. Hepatitis B surface antigen positive cases were labeled as hepatitis B virus-CLD, and all other etiologies as non-HBV-related CLD. Patients were tested for exposure to hepatitis A (total anti-hepatitis A virus [HAV], immunoglobulin M anti-HAV), hepatitis B (hepatitis B surface antigen, total anti-hepatitis B core, anti-hepatitis B surface), and hepatitis E (IgG anti-hepatitis E virus). A total of 142 children with CLD (age 9.1 ± 3.7 years, 83 [58.5%] boys) were enrolled. A total of 3.5% (5/142) and 38.7% (55/142) had received HAV and HBV vaccines, respectively. A total of 134 (94.4%) were total anti-HAV positive including 5 postimmunization patients, with higher positivity in those older than 5 years (19/25 vs 115/117; P = 0.001). Of the 115 patients with non-HBV-related CLD, 45 (39.1%) had exposure to HBV (40 total anti-hepatitis B core positive and 5 anti-HBs positive without immunization). Only 28 of 142 (19.7%) patients were IgG anti-HEV positive, with no difference across age. A total of 90.8%, 39.1%, and 19.7% of children with CLD from the developing world are exposed to hepatitis A, B, and E infections, respectively. Selective hepatitis A vaccination (patients younger than 5 years of age) and universal hepatitis B vaccination are required to protect children with CLD. Sanitation improvement and HEV vaccine trial are needed for prevention against HEV.

Consensus on updating immunizations in patients with primary immunodeficiencies

PubMed

2018-04-01

Las inmunodeficiencias primarias (IDP) constituyen un grupo de enfermedades hereditarias que afectan el número y/o la función de los distintos componentes del sistema inmune. Su prevalencia es de 1:1000-2000 nacimientos. Comprenden defectos de la inmunidad adaptativa, defectos de la inmunidad innata, inmunodeficiencias con fenotipos característicos, trastornos de la regulación inmune, síndromes autoinflamatorios, defectos de los fagocitos y del sistema del complemento y defectos considerados fenocopias de IDP. La vacunación con vacunas inactivadas es segura y puede ser efectiva en muchas inmunodeficiencias; las vacunas vivas atenuadas pueden no ser protectoras en ciertas IDP o presentarse como enfermedad vacunal asociada a la inmunización, lo que conlleva una alta morbimortalidad. Con el objetivo de actualizar las recomendaciones de vacunas en pacientes con IDP, el Comité Nacional de Infectología y el Grupo de Trabajo de Inmunología trabajaron sobre las vacunas que podían indicarse a estos pacientes, convivientes y el equipo de salud.

Two distinct subtypes of hepatitis B virus-related acute liver failure are separable by quantitative serum immunoglobulin M anti-hepatitis B core antibody and hepatitis B virus DNA levels.

PubMed

Dao, Doan Y; Hynan, Linda S; Yuan, He-Jun; Sanders, Corron; Balko, Jody; Attar, Nahid; Lok, Anna S F; Word, R Ann; Lee, William M

2012-03-01

Hepatitis B virus (HBV)-related acute liver failure (HBV-ALF) may occur after acute HBV infection (AHBV-ALF) or during an exacerbation of chronic HBV infection (CHBV-ALF). Clinical differentiation of the two is often difficult if a previous history of HBV is not available. Quantitative measurements of immunoglobulin M (IgM) anti-hepatitis B core antibody (anti-HBc) titers and of HBV viral loads (VLs) might allow the separation of AHBV-ALF from CHBV-ALF. Of 1,602 patients with ALF, 60 met clinical criteria for AHBV-ALF and 27 for CHBV-ALF. Sera were available on 47 and 23 patients, respectively. A quantitative immunoassay was used to determine IgM anti-HBc levels, and real-time polymerase chain reaction (rtPCR) was used to determine HBV VLs. AHBV-ALFs had much higher IgM anti-HBc titers than CHBV-ALFs (signal-to-noise [S/N] ratio median: 88.5; range, 0-1,120 versus 1.3, 0-750; P < 0.001); a cut point for a S/N ratio of 5.0 correctly identified 44 of 46 (96%) AHBV-ALFs and 16 of 23 (70%) CHBV-ALFs; the area under the receiver operator characteristic curve was 0.86 (P < 0.001). AHBV-ALF median admission VL was 3.9 (0-8.1) log10 IU/mL versus 5.2 (2.0-8.7) log10 IU/mL for CHBV-ALF (P < 0.025). Twenty percent (12 of 60) of the AHBV-ALF group had no hepatitis B surface antigen (HBsAg) detectable on admission to study, wheras no CHBV-ALF patients experienced HBsAg clearance. Rates of transplant-free survival were 33% (20 of 60) for AHBV-ALF versus 11% (3 of 27) for CHBV-ALF (P = 0.030). AHBV-ALF and CHBV-ALF differ markedly in IgM anti-HBc titers, in HBV VLs, and in prognosis, suggesting that the two forms are, indeed, different entities that might each have a unique pathogenesis. Copyright © 2011 American Association for the Study of Liver Diseases.

Solenoptera Audinet-Serville, 1832 (Coleoptera, Cerambycidae, Prioninae, Solenopterini) in Cuba, with description of a new species.

PubMed

Devesa, Sergio; Fonseca, Elier; Barro, Alejandro

2016-11-02

The genus Solenoptera Audinet-Serville in Cuba is reviewed and S. zayasi sp. nov. is described from Cuba. The following nomenclatural changes are proposed: 1) S. fraudulenta Galileo & Martins, 1993 is synonymized with S. dominicensis Gahan, 1890; 2) S. cubana (Zayas, 1975) is transferred from Prosternodes cubanus Zayas, 1975. Furthermore, S. dominicensis is removed from the Cuban fauna and new localities for S. cubana are recorded. A key to all three Solenoptera species known from Cuba, both for males and females, is included.

Characterization of anti-liver-kidney microsome antibody (anti-LKM1) from hepatitis C virus-positive and -negative sera.

PubMed

Yamamoto, A M; Cresteil, D; Homberg, J C; Alvarez, F

1993-06-01

Hepatitis C virus-related antibodies were found in sera positive for antibodies to liver/kidney microsome antibody, usually considered a marker of autoimmune hepatitis. The aim of this study was to analyze the specificity of this autoantibody in sera from patients with and without hepatitis C virus infection. Fifteen anti-hepatitis C virus- and anti-liver kidney microsome-positive sera were compared with 11 sera from patients with autoimmune hepatitis, for reactivity against rat and human liver microsomal proteins, P450IID6 recombinant proteins, and various synthetic peptides spanning the 241-429 amino acids sequence of the P450IID6. Ten of 11 sera from patients with autoimmune hepatitis bound to recombinant proteins spanning the P450IID6 region between amino acids 72 and 458. These sera bound to the 254-271 peptide, and some also recognized the 321-351, 373-389 and 410-429 peptides. Four of 15 antihepatitis C virus recognized the fusion protein coded by the full-length P450IID6 complementary DNA; 3 of them also reacted with the P450IID6 region between amino acids 72-456. Only 1 sera recognized the 321-351 peptide. P450IID6 antigenic sites recognized by anti-hepatitis C virus-positive sera were different from those recognized by sera from patients with autoimmune hepatitis.

Experiences of the Dresdner Cord Blood Bank, supported by the Deutsche Knochenmarkspenderdatei.

PubMed

Ordemann, R; Petzold, K; Hölig, K; Schaffer, B; Mauersberger, S; Ehninger, G; Ehminger, G

1999-01-01

Allogeneic bone marrow and peripheral blood stem cell transplantation is the treatment of choice for some malignant hematologic diseases, marrow failure syndromes, and severe congenital immunodeficiency states. Since Gluckman et al reported in 1988 the first successful human leukocyte antigen (HLA)-matched sibling umbilical cord blood stem cell transplantation, it has been known that cord blood is a valuable source of hematopoietic stem cells. The Cord Blood Bank at the University Hospital of Dresden was founded in 1997 and started collecting, processing, and cryoconserving umbilical cord blood in August 1997. The cord blood bank is supported by the largest German donor registry: Deutsche Knochenmarkspenderdatei (DKMS) in Tubingen, Germany. With the informed consent of the mothers, the collection is performed in collaboration with six hospitals in Dresden, Berlin, and Bautzen. We routinely perform a volume reduction by centrifuging the blood bag and expressing the leukocyte-rich supernatant. Routinely, sterility, total nucleated cells (TNC), CD34+ cell count, HLA class I and II, ABO/Rh blood group, and colony-forming units are evaluated. The maternal blood is screened for anti-immunodeficiency virus (anti-HIV), anti-hepatitis C virus (anti-HCV), anti-hepatitis B surface antigen (HBsAg), anti-hepatitis B surface (anti-HBs), anti-hepatitis B core (anti-HBc), anticytomegalovirus (anti-CMV), and toxoplasmosis and with Treponema pallidum hemagglutination assay (TPHA). More than 1,000 cord blood units could be collected. Because of the required volume and cell count and because of sterility, 50% of the collected units had to be discharged. Our results are comparable with data of other cord blood banks: mean volume 79 mL; cell count after volume reduction-TNC, 7.16 x 10(8); mononucleated cells (MNC), 3.75 x 10(8); CD34+ cells, 1.95 x 10(6); colony-forming units (CFU), 67.1 x 10(4). To increase the pool of potential umbilical cord blood units and in order to evaluate the

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koizumi, Yoshiki; Nakajim, Syo; Ohash, Hirofumi

Cell culture study combing a mathematical model and computer simulation quantifies the anti-hepatitis C virus drug efficacy at any concentrations and any combinations in preclinical settings, and can obtain rich basic evidences for selecting optimal treatments prior to costly clinical trials.

Distribution of antibody to hepatitis A antigen in a population of commerical plasma doners.

PubMed

Hall, W T; Mundon, F K; Madden, D L; DeSouza, D; Kane, J L

1977-08-01

Plasma samples from 245 regular plasma donors for Plasma Alliance, Inc. (Knoxville, Tenn.) were tested for the presence of antibody to hepatitis A antigen. Antibody was detected at an immune adherence hemagglutination titer of 1:10 or greater in 37% (91 of 245) of the donors. A statistically significant difference in the frequency of anti-hepatitis A was found between the 18- to 29-year-old group (30%) and the 30- to 49-year-old group (57%). No significant differences between whites and blacks or males afemales were observed. Eighty percent of the donors were in the age range of 18 to 29 years, whereas 48% of the higher-titered plasmas (1:1,000 or greater) were in the 30 to 49 age group. By preselection of donors, it would be possible to produce an immune serum globulin with a specific anti-hepatitis A titer.

Prevalence of hepatitis C virus infection among HIV+ men who have sex with men: a systematic review and meta-analysis.

PubMed

Jordan, Ashly E; Perlman, David C; Neurer, Joshua; Smith, Daniel J; Des Jarlais, Don C; Hagan, Holly

2017-02-01

Since 2000, an increase in hepatitis C virus infection among HIV-infected (HIV+) men who have sex with men has been observed. Evidence points to blood exposure during sex as the medium of hepatitis C virus transmission. Hepatitis C virus prevalence among HIV + MSM overall and in relation to injection drug use is poorly characterized. In this study, a systematic review and meta-analysis examining global hepatitis C virus antibody prevalence and estimating active hepatitis C virus prevalence among HIV + MSM were conducted; 42 reports provided anti-hepatitis C virus prevalence data among HIV + MSM. Pooled prevalence produced an overall anti-hepatitis C virus prevalence among HIV + MSM of 8.1%; active HCV prevalence estimate was 5.3%-7.3%. Anti-hepatitis C virus prevalence among injection drug use and non-injection drug use HIV + MSM was 40.0% and 6.7%, respectively. Among HIV + MSM, hepatitis C virus prevalence increased significantly over time among the overall and non-injection drug use groups, and decreased significantly among injection drug use HIV + MSM. We identified a moderate prevalence of hepatitis C virus among all HIV + MSM and among non-injection drug use HIV + MSM; for both, prevalence was observed to be increasing slightly. Pooled prevalence of hepatitis C virus among HIV + MSM was higher than that observed in the 1945-1965 US birth cohort. The modest but rising hepatitis C virus prevalence among HIV + MSM suggests an opportunity to control HCV among HIV + MSM; this combined with data demonstrating a rising hepatitis C virus incidence highlights the temporal urgency to do so.

Far Away from the Revolution: Understanding the Cuban Revolutionary Armed Forces Mission Changes

DTIC Science & Technology

2011-12-01

municipalities), Plan for Entrepreneurial Redesign, CIMEX (import/export, free-trade zones, tourism, transportation, digital communications equipment, car...rentals and audiovisual publicity), CUBANA-CAN (similar to CIMEX ), Citrus (agricultural and industrial processing), State Commission for

Difficulties in Diagnosing Sexual Abuse in Children with Condyloma Acuminata in Turkey

ERIC Educational Resources Information Center

Bulbul, Selda; Demirceken, Fulya; Cakir, Baris; Cakir, Elif Pinar; Unlu, Erdal; Soyer, Tutku

2010-01-01

Human papillomavirus is responsible for anogenital warts and could be regarded as an indicator of possible sexual abuse in children. A genital wart was detected during an investigation of anti-hepatitis C virus positivity in a four-year-old male patient. No pathological findings of another sexually transmitted disease were found except complete…

Coinfection of hepatitis E virus and other hepatitis virus in Colombia and its genotypic characterization.

PubMed

Peláez, Dioselina; Martínez-Vargas, Daniel; Escalante-Mora, Martha; Palacios-Vivero, Mariel; Contreras-Gómez, Lady

2015-12-04

Hepatitis E virus has emerged as a public health problem, particularly in developing countries. The four genotypes identified in mammals include the G3 found in indigenous hepatitis in countries and regions with high porcine population, and the G1, associated with maternal deaths.  To determine coinfection by hepatitis E virus and the circulating genotypes in Colombia in 1,097 samples using serological markers for hepatitis A, B and C.  Serum samples of 1,097 patients from different regions of Colombia stored at the Laboratorio de Virología of the Instituto Nacional de Salud were selected to detect IgG and IgM anti-hepatitis E virus antibodies. The viral genomes of positive samples were amplified by RT-PCR, and the products were sequenced and phylogenetically analyzed by comparing ORF2 sequences deposited in the GenBank.  IgG anti-hepatitis E virus antibodies were found in 278 samples, IgM in 62, and both markers in 64. Hepatitis E virus and hepatitis A virus coinfection determined by IgG anti-hepatitis E virus was 33.6% and 16.1% by IgM; hepatitis E virus and hepatitis B virus coinfection was 23.4% and 8.1%, and hepatitis E virus and hepatitis C virus coinfection was 35.4% and 5.83%, respectively. Among the 52 positive samples by PCR nine were sequenced and grouped within genotype 3A of the American porcine strain.  The highest seropositivity was observed for hepatitis A and E. The incidence of hepatitis E virus coinfection with other hepatotropic viruses indicated that this pathogen is more frequent than expected. The circulation of genotype 3A implies that this disease may occur in outbreaks and as zoonosis in Colombia.

Cuban Telecommunications, Computer Networking, and U.S. Policy Implications,

DTIC Science & Technology

1996-07-01

Informacion para la Prensa Federacion de Mujeres Cubanas Grupo para la Educacion sobre el SIDA Instituto Superior Latinoamericano de Ajedrez...DIR) Informacion sobre Medio Ambiente (DIR) Medicina Alternativa (DIR) Servicio Especial de la Mujer (DIR) Eventos Internacionales (DIR

Immunization Schedules for Adults

MedlinePlus

... color [2 pages] PDF black & white [2 pages] Spanish Version (en español) Vacunas recomendadas para adultos según ... easy-to-read format in English and/or Spanish on your website. See examples of how the ...

Hepatitis B Vaccine: What You Need to Know

MedlinePlus

... información sobre vacunas están disponibles en español y en muchos otros idiomas. Visite www. immunize. org/ vis 1 Why get vaccinated? Hepatitis B is a serious disease that affects the liver. ...

Long-Term Health Effects of Repeated Exposure to Multiple Vaccines

DTIC Science & Technology

2004-01-01

0.945 Hepatits B surface antigen 0.0% 0.0% NT Anti-hepatitis C antibody 0.0% 2.0% 1.000 HLA - B27 9.8% 10.6% 0.868 NT, not tested. a Tests are two-tailed...536 The distribution of markers for hepatitis A, hepatitis B, hepatitis C, and HLA B27 was similar between groups (Table 1), supporting comparability

Multicentric Evaluation of New Commercial Enzyme Immunoassays for the Detection of Immunoglobulin M and Total Antibodies against Hepatitis A Virus▿

PubMed Central

Arcangeletti, M. C.; Dussaix, E.; Ferraglia, F.; Roque-Afonso, A. M.; Graube, A.; Chezzi, C.

2011-01-01

A multicentric clinical study was conducted on representative sera from 1,738 European and U.S. subjects for the evaluation of new anti-hepatitis A virus enzyme immunoassays from Bio-Rad Laboratories. Comparison with reference DiaSorin S.p.A. tests confirmed the good performance of Bio-Rad assays (99.85% and 99.47% overall agreement in detecting total antibodies and IgM, respectively). PMID:21653739

Cuba: Issues for 111th Congress

DTIC Science & Technology

2009-04-14

Humanos y Reconciliacion Nacional, “Cuba en el año 2009: la situacíon de derechos civiles, políticos y económicos,” February 2, 2009. 13 Anita Snow...park. On April 21, 2008, ten members of the Ladies in White were 12 Comision Cubana de Derechos

Cuba: Issues for the 111th Congress

DTIC Science & Technology

2009-03-18

April 21, 2008, ten members of the Ladies in White were 12 Comision Cubana de Derechos Humanos y...Reconciliacion Nacional, “Cuba en el año 2009: la situacíon de derechos civiles, políticos y económicos,” February 2, 2009. 13 Anita Snow, “Cuban

Immunogenicity of aluminum-adsorbed hepatitis A vaccine (Havrix®) administered as a third dose after primary doses of Japanese aluminum-free hepatitis A vaccine (Aimmugen®) for Japanese travelers to endemic countries.

PubMed

Fukushima, Shinji; Kiyohara, Tomoko; Ishii, Koji; Nakano, Takashi; Hamada, Atsuo

2017-11-07

Hepatitis A vaccination is recommended for travelers to endemic countries. Several inactivated aluminum-adsorbed hepatitis A vaccines are available worldwide, but only one licensed hepatitis A vaccine is available in Japan. This vaccine is a lyophilized inactivated aluminum-free hepatitis A vaccine (Aimmugen®). The standard schedule of Aimmugen® is three doses (at 0, 2-4 weeks, and 6 months). Japanese people will go abroad after receiving 2 doses of Aimmugen®. Some long-term travelers will receive the third dose of hepatitis A vaccine at their destination, at 6-24 months after 2 doses of Aimmugen®. Aimmugen® is not available in countries other than Japan. They receive inactivated aluminum-adsorbed hepatitis A vaccine instead of a third dose of Aimmugen®. This study was undertaken to determine whether the booster vaccination with an aluminum-adsorbed hepatitis A vaccine is effective following two doses of Aimmugen®. Subjects were healthy Japanese adults aged 20 years or older who had received two doses of Aimmugen®. Subjects received a booster dose of Havrix®1440 intramuscularly as the third dose. Serology samples for hepatitis A virus antibody titers were taken 4-6 weeks later. Anti-hepatitis A virus antibody titers were measured by an inhibition enzyme-linked immunosorbent assay. Subjects were 20 healthy Japanese adults, 6 men and 14 women. The mean age ± standard deviation was 37.2 ± 13.3. The seroprotection rate (SPR, anti-hepatitis A virus antibody titer ≥10 mIU/mL) was 85% at enrollment, and increased to 100% after vaccination with Havrix®. The geometric mean anti-hepatitis A virus antibody titer increased from 39.8 mIU/mL to 2938.2 mIU/mL. The three scheduled doses consisting of two doses of Aimmugen® plus a third dose with Havrix® is more immunogenic than using only two doses of Aimmugen®. The vaccination with Havrix® could be allowed to be used instead of a third dose of Aimmugen®. (UMIN000009351). Copyright © 2017 Elsevier Ltd. All

Liver cancer risk, coffee, and hepatitis C virus infection: a nested case–control study in Japan

PubMed Central

Wakai, K; Kurozawa, Y; Shibata, A; Fujita, Y; Kotani, K; Ogimoto, I; Naito, M; Nishio, K; Suzuki, H; Yoshimura, T; Tamakoshi, A

2007-01-01

We examined hepatocellular carcinoma mortality in relation to coffee consumption and anti-hepatitis C virus (HCV) antibody seropositivity in a nested case–control study involving 96 cases. The multivariate-adjusted odds ratios (95% confidence interval) for daily coffee drinkers vs non-drinkers were 0.49 (0.25–0.96), 0.31 (0.11–0.85), and 0.75 (0.29–1.92) in all cases, in HCV-positive and in HCV-negative individuals, respectively. PMID:17637681

Pay attention to the study on active antiliver fibrosis components of Chinese herbal medicine.

PubMed

Hu, Yi-Yang

2012-08-01

In this review, the researches on Chinese herb components with anti-hepatic fibrosis activity in China in the recent 20 years were generalized. Almost thirty active herb components attracted author's attention, especially, salvianolic acid B and oxymatrine which were investigated comprehensively. Moreover, the author considered that, in view of the complex pathogenesis and the multi-pathway and multi-target superiority of Chinese medicine formula, the effective components formula investigations deserve more attention and probably prompt a potential researching direction.

Draft Genome Sequences of Two Novel Salmonella enterica subsp. enterica Strains Isolated from Low-Moisture Foods with Applications in Food Safety Research.

PubMed

Radford, Devon R; Leon-Velarde, Carlos G; Chen, Shu; Hamidi Oskouei, Amir M; Balamurugan, Sampathkumar

2018-03-29

The genomes of two strains of Salmonella enterica subsp. enterica serovar Cubana and serovar Muenchen, isolated from dry hazelnuts and chia seeds, respectively, were sequenced using the Illumina MiSeq platform, assembled de novo using the overlap-layout-consensus method, and aligned to their respective most identical sequence genome scaffolds using MUMMER and BLAST searches. Copyright © 2018 Radford et al.

Changing patterns of hepatitis A and E sero-prevalences in children after the 1999 earthquakes in Duzce, Turkey.

PubMed

Kaya, Ayse Demet; Ozturk, C Elif; Yavuz, Taner; Ozaydin, Cigdem; Bahcebasi, Talat

2008-04-01

Hepatitis A and E are enteric viral diseases that are characteristically found in developing countries. Sero-epidemiological data about both infections showed higher prevalence rates soon after the 1999 earthquakes in Duzce, Turkey. The aim of the present study was to evaluate the data 4 years after the earthquakes. The study group included 589 children (72.3% boys) who were between the ages of 6 months and 17 years (mean age 11.5 years). The children were separated into three groups: Group 1 (ages 6 months to 5.9 years), Group 2 (ages 6.0-12.9 years) and Group 3 (ages 13.0-17.0 years). Serum anti-hepatitis A virus IgG and anti-hepatitis E virus IgG were determined using commercial enzyme-linked immunosorbent assay kits. The data were tested for statistical significance with the chi(2)-test. The sero-prevalence rates of hepatitis A and E were 63.8% and 0.3%, respectively. The sero-prevalence rates of both hepatitis A and E increased with age, and there was no significant difference between the genders. Hepatitis A infection was associated with socio-economic condition, crowded living environment, and education level of the family (P < 0.01). Hepatitis A infection is still common, whereas hepatitis E infection appears to be relatively rare in paediatric age groups in Duzce, Turkey.

Hepatitis A as an etiologic agent of acute liver failure in Latin America.

PubMed

Ciocca, Mirta; Moreira-Silva, Sandra Fagundes; Alegría, Sylvia; Galoppo, Maria Cristina; Ruttiman, Ricardo; Porta, Gilda; Da Silvera, Themis Reverbel; Rubio, Pilar; Macias, Mercedes; Cervantes, Yolanda; Avila-Aguero, Maria Luisa; Clemens, Sue Anne Costa; Clemens, Ralf; Weil, John

2007-08-01

This prospective, multicenter study examined the importance of hepatitis viruses as etiological agents of acute liver failure (ALF) and the outcome of ALF cases in Latin American children and adolescents. The study was conducted for minimum 12 months in 9 centers in Argentina, Brazil, Chile, Colombia, Costa Rica, and Mexico during 2001-2002. Hospitalized patients aged 1-20 years with a suspected diagnosis of ALF were included in the study and tested for serologic markers for hepatitis A, B, and C viruses. Of the 106 patients enrolled, 88 were included in the analysis. Median age was 5 years, and 55% with ALF were aged 1-5 years. A total of 37 individuals (43%) tested positive for anti-hepatitis A virus (HAV) immunoglobulin M (IgM) as marker of acute HAV infection; one was positive for anti-hepatitis B core antigen IgM and negative for hepatitis B surface antigen. None had markers of hepatitis C virus infection. Mortality rates in the overall study cohort (45%) and for those who tested anti-HAV IgM positive (41%) were similar. Forty-one percent of all patients and 46% of those positive for anti-HAV IgM underwent transplantation. The mortality rate in those with liver transplantation was half of that in patients who were not transplanted (28% versus 57%). HAV was the main etiologic agent of ALF in the population studied.

Epidemiological study of hepatitis A, B and C in the largest Afro-Brazilian isolated community.

PubMed

Matos, Márcia A D; Reis, Nádia Rúbia S; Kozlowski, Aline G; Teles, Sheila A; Motta-Castro, Ana Rita C; Mello, Francisco C A; Gomes, Selma A; Martins, Regina M B

2009-09-01

This study was conducted to estimate the prevalence and molecular epidemiological features of viral hepatitis A, B and C in the Kalunga population, which represents the largest Afro-Brazilian isolated community. Among 878 individuals studied, the overall prevalence of anti-hepatitis A virus antibodies was 80.9%, with a significant rise from 44.8% to near 100% between the first and fourth decade of life. Rates for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc) of 1.8% and 35.4%, respectively, were found. Increasing age, male gender, illiteracy and history of multiple sexual partners were associated with hepatitis B virus (HBV) infection. An occult HBV infection rate of 1.7% (5/295) was found among anti-HBc-positive individuals. HBV genotype A (subtype Aa) was dominant in this community. Only 5/878 individuals (0.6%) were positive for anti-hepatitis C virus (HCV). HCV RNA was detected in three of them, who were infected with genotype 1 (subtype 1a). These findings point out high, intermediate and low endemicity for hepatitis A, B and C, respectively, in the Kalunga community in Brazil. Circulation of HBV genotype A (subtype Aa) in this Afro-Brazilian isolated community indicates the introduction of this virus during the slave trade from Africa to Brazil.

Seropositive abdominal and thoracic donor organs are largely underutilized.

PubMed

Taylor, R M; Pietroski, R E; Hagan, M; Eisenbrey, A B; Fontana, R J

2010-12-01

The aim of this study was to describe the epidemiology and utilization of anti-hepatitis B core protein(+) and anti-hepatitis C virus(+) organ donor referrals in a large organ procurement organization. Between 1995 and 2006, 3,134 deceased organ donor referrals were tested for anti-HBc and anti-HCV using commercial assays. The prevalence of anti-HCV(+) organ donor referrals significantly increased from 3.4% in 1994-1996 to 8.1% in 2003-2005 (P < .001), whereas the prevalence of anti-HBc(+) organ donor referrals remained unchanged at 3%-4% (P = .20). The 112 anti-HBc(+) (3.5%) and 173 anti-HCV(+) (5.5%) organ donor referrals were significantly older and more likely to be noncaucasian than seronegative organ donor referrals (P < .02). The procurement and utilization rates of seropositive thoracic and abdominal donor organs were significantly lower compared with seronegative organ donors (P < .0001). However, liver utilization rates significantly increased from anti-HBc(+) donors over time (21% vs 46%; P = .026), whereas utilization of anti-HCV(+) liver donors remained unchanged over time (5% vs 18%; P = .303). In summary, the proportion of anti-HCV(+) organ donor referrals has significantly increased and the proportion of anti-HBc(+) organ donor referrals has remained stable. Both thoracic and abdominal organs from seropositive donors are largely underutilized. Copyright © 2010 Elsevier Inc. All rights reserved.

Recent Trends and Future Prospects of Terrorism in the United States

DTIC Science & Technology

1988-05-01

34 violence. Two Puerto Rican terror- ist groups, the Comandos Armados de Liberacion (Armed Commandos of Liberation) and the Movimiento de Independencia...Cuban Nationalist Movement, the FLNC (Frente de Liberacion Nacional Cubana, or Cuban National Liberation Front), and Omega-7. 11 12 RECENT TRENDS AND...island. Most of this activity has been carried out by either the FALN (Fuerzas Armadas de Liberacion Nacional, or Armed Forces of the National

International Terrorism: A Chronology (1974 Supplement)

DTIC Science & Technology

1976-02-01

France and BeJgium by GARI--Grupo de Acci6n Revolucionaria Internacionalista (Interna- tional Revolutionary Action Group), an anti-Franco, anarcho...Right-wing extremists calling themselves the ((Youth Action Group" and ((Group for the De - fense of Europe" claimed responsibility for a series of...extremists also increased their activities, as an organization calling itself the FLNG-Frente de Liberaci6n Nacional Cubana (Cuban National Liberation

Hepatitis B core antigen antibody as an indicator of a low grade carrier state for hepatitis B virus in a Saudi Arabian blood donor population.

PubMed

Bernvil, S S; Andrews, V; Kuhns, M C; McNamara, A L

1997-03-01

Blood donor screening for anti-hepatitis B core antigen (anti-HBc) was introduced as a surrogate marker of non-A, non-B hepatitis prior to the availability of a specific test for hepatitis C. In areas endemic for hepatitis B virus (HBV), such as Saudi Arabia, earlier studies indicated that up to 30% of blood donors might disqualify if screened for anti-HBc. The issue was readdressed in a study of 6035 consecutive first-time Saudi national blood donors in an attempt to identify a subgroup of anti-HBc positive donors who might be at high risk of being low grade carriers of HBV. An isolated anti-HBc of high titer in a donor with a low or absent anti-hepatitis B surface antigen (anti-HBsAg) was taken as an indicator of increased risk of a low grade carrier state. Using this algorithm, an additional 125 (2%) donors would disqualify. HBsAg immune complex assays and polymerase chain reaction of donor samples with an isolated anti-HBc identified two donors with immune complexes and two donors with HBV DNA. All four donor samples expressed over 90% neutralization in the anti-HBc supplementary testing, indicating high titer anti-HBc. These findings seem to support the suggested policy of donor exclusion based on the anti-HBc and anti-HBsAg serology as a means to eliminate low grade carriers of HBV in endemic areas without jeopardizing the blood supply.

A Randomized Controlled Trial to Evaluate a Potential Hepatitis B Booster Vaccination Strategy Using Combined Hepatitis A and B Vaccine.

PubMed

Li, Fangjun; Hu, Yuansheng; Zhou, Youming; Chen, Lixin; Xia, Wei; Song, Yufei; Tan, Zhengliang; Gao, Lidong; Yang, Zhong; Zeng, Gang; Han, Xing; Li, Junhua; Li, Jing

2017-05-01

Booster doses could play a major role in no responders or low responders to primary hepatitis B (HB) vaccine. Planed time point for hepatitis A vaccination in China provides a good opportunity to carry out HB booster dose by using combined hepatitis A and B vaccine. A randomized, double-blinded clinical trial was conducted to compare the immunogenicity and safety of toddlers 18-24 months of age receiving 3 different vaccination regimens: 2 doses of inactivated hepatitis A vaccine (group 1), 1 dose of inactivated hepatitis A vaccine plus 1 dose of combined hepatitis A and B vaccine (group 2) or 2 doses of combined hepatitis A and B vaccine (group 3). All 3 groups showed 100% seroprotection for antihepatitis A virus antibody after vaccination. Seroprotection rate for anti-HB antibody before vaccination ranged from 79.5% to 92.9% in the 3 groups. After second inoculation, anti-HBs seroprotection increased from 92.9% to 100% in group 2 with postvaccination geometric mean concentration (GMC) of 2258.3 mIU/mL and from 79.5% to 98.9% in group 3 with postvaccination GMC of 2055.3 mIU/mL. The adverse events were not statistically different among groups (P = 0.345). Combined hepatitis A and B vaccine could stimulate high level of both antihepatitis A virus and anti-HBs antibodies and not increase adverse events, providing a new choice for HB booster.

Immune Responses and Protection of Aotus Monkeys Immunized with Irradiated Plasmodium vivax Sporozoites

DTIC Science & Technology

2011-01-01

The experimental protocol was approved by the Animal Ethical Committee of the Universidad del Valle (Cali). Parasite and irradiation. Plasmodium...three repeats ofpll (GDRADGPA) and (ANGAGNQPG) sequences, derived from VK210 and VK247 CS variants, respectively. A non-malaria related peptide Ptt30...Universidad del Valle and Centro Internacional de Vacunas, Cali, Colombia, E-mails: alejovi@hotmail.com, anbonelo@yahoo.com, alejcaste@yahoo.com

Raltegravir Pharmacokinetics in Patients on Asunaprevir-Daclatasvir

PubMed Central

Vincent, Corine; Furlan, Valérie; Rosa, Isabelle; Rosenthal, Eric; Cheret, Antoine; Molina, Jean-Michel; Taburet, Anne-Marie; Piroth, Lionel

2015-01-01

Raltegravir pharmacokinetics was studied in 20 patients included in the ANRS HC30 QUADRIH Study before and after addition of anti-hepatitis C virus (anti-HCV) quadritherapy, including pegylated-interferon–ribavirin and asunaprevir plus daclatasvir. Raltegravir pharmacokinetic parameters remained unchanged whether administered on or off anti-HCV therapy. In addition, concentrations of raltegravir, asunaprevir, and daclatasvir were not affected by liver cirrhosis. These data suggest that in human immunodeficiency virus (HIV)-HCV-coinfected patients, whether cirrhotic or not, asunaprevir and daclatasvir could be administered safely with raltegravir. PMID:26438504

Long-term antibody response and immunologic memory in children immunized with hepatitis B vaccine at birth.

PubMed

Saffar, M J; Rezai, M S

2004-12-01

Four hundred and fifty three healthy children immunized with a course of hepatitis B vaccine beginning at birth were tested at 10-11 years of age for persistence of anti-hepatitis B-S antigen antibody (anti-HBs); and responses of children without protective antibody to different doses of hepatitis B vaccine booster were evaluated. Although nearly 42% of them were not seroprotected, but most of boosted subjects (87.3%) retained robust immunologic memory and rapidly retained a protective anti-HBs antibody titer of at least 10 IU/L after booster vaccination.

Studies to Control Endemic Typhoid Fever in Chile

DTIC Science & Technology

1982-01-29

de las colecistopatias en Chile . Rev.Med.Chile 100:1376- 1381, 1972. 8. Medina, E., Kaempffer, A.M., DeCroizet, V.A., Yrrazaval, Toporowicz, M...Epidemoologia de las colecistopatias en Chile . II. Factores de importancia en estudios de autopsia. Rev.Med.Chile 100:1382-1389, 1972. 9. Marinovio, I...necesario ef ec tuar previamente ex5menes bactereol.’gicos de inocuidad y potencia_ de la vacuna en el Instituto de Salud Priblica de

Synthesis, Anti-HCV, Antioxidant and Reduction of Intracellular Reactive Oxygen Species Generation of a Chlorogenic Acid Analogue with an Amide Bond Replacing the Ester Bond.

PubMed

Wang, Ling-Na; Wang, Wei; Hattori, Masao; Daneshtalab, Mohsen; Ma, Chao-Mei

2016-06-08

Chlorogenic acid is a well known natural product with important bioactivities. It contains an ester bond formed between the COOH of caffeic acid and the 3-OH of quinic acid. We synthesized a chlorogenic acid analogue, 3α-caffeoylquinic acid amide, using caffeic and quinic acids as starting materials. The caffeoylquinc acid amide was found to be much more stable than chlorogenic acid and showed anti-Hepatitis C virus (anti-HCV) activity with a potency similar to chlorogenic acid. The caffeoylquinc acid amide potently protected HepG2 cells against oxidative stress induced by tert-butyl hydroperoxide.

Lichen planus, liver kidney microsomal (LKM1) antibodies and hepatitis C virus antibodies.

PubMed

Divano, M C; Parodi, A; Rebora, A

1992-01-01

No anti-liver kidney microsomal (LKM1) antibodies were detected in 46 patients with LP, 16 of whom had also a chronic liver disease (CLD). In contrast, anti-hepatitis C virus (HCV) antibodies were found in 10% of patients with LP and in 50% of those with LP and CLD. Anti-HCV antibodies may be considered as a false-positive reaction in 56% of cases, especially when anti-LKM1 antibodies are present. Our findings do not support such a hypothesis, but suggest that CLD in LP patients is, at least in Italy, mostly a postviral chronic active hepatitis.

Liver transplantation from anti-hepatitis C virus-positive donors: our experience.

PubMed

Álvaro, E; Abradelo, M; Fuertes, A; Manrique, A; Colina, F; Alegre, C; Calvo, J; García, M; García-Sesma, A; Cambra, F; Sanabria, R; Moreno, E; Jimenez, C

2012-01-01

Hepatitis C (HCV) is among the most common causes of end-stage liver disease worldwide. The donor shortage leads us to consider alternative organ sources such as HCV-positive donors. The outcomes of these transplants must be evaluated thoroughly since there is universal recurrence of disease among HCV-positive liver transplant recipients. From January 2005 to April 2011, we performed 143 liver transplants (OLT) to treat end-stage liver disease secondary to HCV infection. Thirteen patients (9,1%) received livers from HCV-positive donors. A control group consisted of 130 HCV-positive patients who underwent OLT during the same period with organs from HCV-negative donors. Donor HCV status was assessed by 2 tests: HCV antibodies and viral load. Not only recipient and graft survivals were analyzed, but also frequency, timing and severity of hepatitis recurrence. Among 143 transplants performed in HCV-positive recipients during a 6-year period from January 1, 2005, to April 30, 2011, 9.1% of patients received an organ from an anti-HCV-positive donor, 72.7% of whom showed a negative viral load. The vast majority (80%) of our patients suffered hepatitis during their follow-up, 22.4% of which were severe cases. No significant difference in patient or graft survival was observed between the 2 groups. A high percentage of grafts with initial positive serology for HCV showed no viral replication. Grafts from HCV-positive donors can be considered to be a safe, effective source for liver donation. Copyright © 2012 Elsevier Inc. All rights reserved.

A public-professional web-bridge for vaccines and vaccination: user concerns about vaccine safety.

PubMed

García-Basteiro, Alberto L; Alvarez-Pasquín, María-José; Mena, Guillermo; Llupià, Anna; Aldea, Marta; Sequera, Victor-Guillermo; Sanz, Sergi; Tuells, Jose; Navarro-Alonso, José-Antonio; de Arísteguí, Javier; Bayas, José-María

2012-05-28

Vacunas.org (http://www.vacunas.org), a website founded by the Spanish Association of Vaccinology offers a personalized service called Ask the Expert, which answers any questions posed by the public or health professionals about vaccines and vaccination. The aim of this study was to analyze the factors associated with questions on vaccination safety and determine the characteristics of questioners and the type of question asked during the period 2008-2010. A total of 1341 questions were finally included in the analysis. Of those, 30% were related to vaccine safety. Questions about pregnant women had 5.01 higher odds of asking about safety (95% CI 2.82-8.93) than people not belonging to any risk group. Older questioners (>50 years) were less likely to ask about vaccine safety compared to younger questioners (OR: 0.44, 95% CI 0.25-0.76). Questions made after vaccination or related to influenza (including H1N1) or travel vaccines were also associated with a higher likelihood of asking about vaccine safety. These results identify risk groups (pregnant women), population groups (older people) and some vaccines (travel and influenza vaccines, including H1N1) where greater efforts to provide improved, more-tailored vaccine information in general and on the Internet are required. Copyright © 2011 Elsevier Ltd. All rights reserved.

The use of Chinese herbal medicines associated with reduced mortality in chronic hepatitis B patients receiving lamivudine treatment.

PubMed

Tsai, Der-Shiang; Huang, Mei-Hsuen; Chang, Yuan-Shiun; Li, Tsai-Chung; Peng, Wen-Huang

2015-11-04

Lamivudine associated mutation and resistance reduces the effect of anti-hepatitis B virus. Pharmacological studies in cell and animal model suggest that Chinese herbal medicines (CHMs) have anti-hepatitis B virus effect. Observational studies offer mixed results. The aim of this study was to evaluate the relation between the use of CHMs and outcome in patients with chronic hepatitis B receiving lamivudine treatment and further estimate the association of Jia-Wei-Xiao-Yao-Sang (JWXYS) use with mortality of those patients. We conducted a cohort study among patients age 20-90 years within a National Health Insurance Healthcare system. Information on the use of CHMs and covariates were obtained from Taiwan National Health Insurance Research Database. We used Cox proportional hazards models to estimate the hazard ratio and 95% confidence intervals (95% CI) for all-cause mortality among CHMs users compared to nonusers. Among 1037 patients studied from 2004 to 2011, median follow-up time 5.3 years and 88 deaths were identified. During the study period, 49% of patients used CHMs and the median duration of use was 2.4 years. We found that significant difference on all-cause mortality among CHMs users (aHR=0.45, 95% CI: 0.27-0.76) compared to CHMs nonusers. All-cause mortality also differed by JWXYS use (aHR=0.26, 95% CI: 0.08-0.83). This study reveals that the use of CHMs may lower the risk of death in patients with chronic hepatitis B receiving lamivudine treatment. Further randomized-controlled trials are required to validate these findings. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A new inositol triester from Taraxacum mongolicum.

PubMed

Liu, Jifeng; Zhang, Nenling; Liu, Mengqi

2014-01-01

One new inositol triester, 4,5,6-tri-O-p-hydroxyphenylacetyl-chiro-inositol (1), was isolated from the ethanolic extract of Taraxacum mongolicum, along with two known compounds, 11β,13-dihydrotaraxinic acid (2) and taraxinic acid β-d-glucopyranosyl ester (3). The isolates were tested for their anti-hepatitis B virus (HBV) activities; 11β,13-dihydrotaraxinic acid (2) exhibited an IC50 value of 0.91 mM inhibiting the secretion of the HBV surface antigen and an IC50 value of 0.34 mM inhibiting the secretion of the HBV e antigen using HBV transfected Hep G2.2.15 cell line.

The changing face of the epidemiology of type A, B, and D viral hepatitis in Italy, following the implementation of vaccination.

PubMed

Romanò, Luisa; Paladini, Sara; Tagliacarne, Catia; Zappa, Alessandra; Zanetti, Alessandro Remo

2009-05-26

The morbidity and mortality rates of viral hepatitis A, B and Delta have dramatically dropped in Italy during the last decades. Thanks to the general improvements in hygiene and sanitation, hepatitis A has shifted from a high to an intermediate/low endemicity status. Vaccination against hepatitis A is recommended to people at increased risk, including travellers to endemic areas, military personnel and individuals at occupational risk. The implementation of universal anti-hepatitis B vaccination of infants and adolescents has resulted in a dramatic decline in disease burden and in the carrier rate. An additional benefit of hepatitis B vaccination is that hepatitis Delta has also substantially declined.

Direct Acting Anti-hepatitis C Virus Drugs: Clinical Pharmacology and Future Direction

PubMed Central

Geddawy, Ayman; Ibrahim, Yasmine F.; Elbahie, Nabil M.; Ibrahim, Mohammad A.

2017-01-01

Abstract Chronic hepatitis C virus (HCV) infection is a leading cause of chronic liver disease. The introduction of direct acting antiviral agents (DAAs) for its treatment represents a major advance in terms of sustained virologic response (SVR) rates and adverse effect profiles. Mechanistically, DAAs inhibit specific HCV non-structural proteins (NS) that are vital for its replication. Boceprevir, telaprevir, simeprevir, asunaprevir, grazoprevir and paritaprevir are NS3/4A inhibitors. Ombitasvir, ledipasvir, daclatasvir, elbasvir and velpatasvir are NS5A inhibitors. Sofosbuvir and dasabuvir are NS5B inhibitors. Currently, a combination of two or more DAAs is the corner stone for the treatment of HCV infection. However, the success of DAA therapy is facing several challenges, including the potential of drug-drug interactions and resistant variance. Moreover, the shortage of relevant clinical pharmacological data and drug interaction regarding DAA is a clinical concern. The present review discusses the clinical pharmacology of DAAs with special emphasis on drug-drug interaction. PMID:28680834

Seroprevalence of anti-hepatitis E virus antibodies in domestic pigs in Mexico.

PubMed

García-Hernández, Montserrat Elemi; Cruz-Rivera, Mayra; Sánchez-Betancourt, José Iván; Rico-Chávez, Oscar; Vergara-Castañeda, Arely; Trujillo, María E; Sarmiento-Silva, Rosa Elena

2017-09-21

Hepatitis E virus (HEV) infection is one of the most common causes of acute liver diseases in humans worldwide. In developing countries, HEV is commonly associated with waterborne outbreaks. Conversely, in industrialized countries, HEV infection is often associated with travel to endemic regions or ingestion of contaminated animal products. Limited information on both, human and animal HEV infection in Mexico is available. As a consequence, the distribution of the virus in the country is largely unknown. Here, we assessed the seroprevalence of HEV among swine in different geographical regions in Mexico. Seroprevalence of anti-HEV antibodies in swine herds in Mexico was evaluated in a representative sample including 945 pig serum specimens from different regions of the country using a commercial enzyme-linked immunosorbent assay (ELISA). The overall prevalence of anti-HEV antibodies in swine was 59.4%. The northern region of Mexico exhibited the highest seroprevalence in the country (86.6%), while the central and southern regions in Mexico showed lower seroprevalence, 42.7% and 51.5%, respectively. In Mexico, HEV seroprevalence in swine is high. Importantly, northern Mexico showed the highest seroprevalence in the country. Thus, further studies are required to identify the risk factors contributing to HEV transmission among pigs in the country. Assessment of HEV human infection in the context of viral transmission in swine is required to better understand the epidemiology of hepatitis E in Mexico.

Routine screening of blood donations at Qingdao central blood bank, China, for hepatitis B virus (HBV) DNA with a real-time, multiplex nucleic acid test for HBV, hepatitis C virus, and human immunodeficiency virus Types 1 and 2.

PubMed

Yang, Zhongsi; Xu, Lei; Liu, Li; Feng, Qiuxia; Zhang, Longmu; Ma, Weijuan; Saldanha, John; Wang, Mingmin; Zhao, Lin

2013-10-01

The Roche cobas TaqScreen MPX test was used to evaluate the rate of hepatitis B surface antigen (HBsAg)-negative donations that were hepatitis B virus (HBV) DNA reactive from June 2010 to January 2011 in Qingdao, China. HBsAg-negative samples from 65,800 voluntary blood donors were tested with the cobas TaqScreen MPX test in pools of 6 on the Roche cobas s 201 blood screening platform. Samples positive for HBV DNA and negative for HBsAg were quantitated with the Roche COBAS AmpliPrep/COBAS TaqMan HBV test. In addition, serologic tests for HBsAg, hepatitis B surface antibody, anti-hepatitis B core antigen (anti-HBc), anti-hepatitis B e antigen (anti-HBe), and hepatitis B e antigen (HBe) were done using the Roche electrochemiluminescence immunoassay. A total of 80 nucleic acid amplification technology (NAT) test-reactive pools were identified and 59 pools (74%) resolved to a reactive sample. All samples were HBV DNA reactive and the viral load in each sample was quantitated. The viral loads of the samples ranged from less than 20 to 34,600 IU/mL; 13 samples (22%) had viral loads of more than 20 IU/mL, 27 samples (45.8%) had viral loads of less than 20 IU/mL, and 19 samples (32.2%) had undetectable viral loads. Of the 59 NAT-reactive samples, 40 (67.8%) were anti-HBc positive. Fifteen of the 59 samples could not be confirmed as NAT reactive either by an alternative NAT test or by serology. The HBV NAT yield in blood donors in Qingdao is 0.06% (38/65,800). This study confirmed the value of NAT for interdicting HBV-positive donations and preventing transfusion-transmitted HBV infections. © 2013 American Association of Blood Banks.

Hepatitis E virus and hepatitis A virus exposures in an apparently healthy high-risk population in Italy.

PubMed

Rapicetta, M; Monarca, R; Kondili, L A; Chionne, P; Madonna, E; Madeddu, G; Soddu, A; Candido, A; Carbonara, S; Mura, M S; Starnini, G; Babudieri, S

2013-02-01

The prevalence of anti-hepatitis E virus (HEV) and anti-hepatitis A virus (HAV), as well as the possible links with socio-demographic and other viral risks factors, were evaluated in an inmates population. The study population consisted of 973 consecutively recruited inmates of eight Italian prisons. The anti-HEV prevalence was 11.6 % (113/973). It increased significantly by age (χ(2) for linear trend: p = 0.001) and was significantly higher among non-Italian compared to Italian inmates (15.3 vs. 10.7 %, respectively). Age >40 years [odds ratio (OR) 2.1; 95 % confidence interval (CI) 1.4-3.1], non-Italian citizenship (OR 1.8; 95 % CI 1.1-2.9) and anti-HIV seropositivity (OR 2.2; 95 % CI 1.2-4.2) were the only factors independently associated to anti-HEV positivity by logistic regression analysis. The overall anti-HAV prevalence was 86.4 %, and was significantly higher in non-Italian compared to Italian prisoners (92.6 vs. 84.9 %, respectively; p = 0.02). Age older than 40 years (OR 3.6; 95 % CI 2.2-5.9), <5 years formal education (OR 2.1; 95 % CI 1.3-3.2) and non-Italian nationality (OR 2.7; 95 % CI 1.5-4.8) were factors independently associated to anti-HAV positivity by the logistic regression analysis. Compared to the general population, significantly higher anti-HEV and anti-HAV prevalences were observed in an inmates population in Italy. Old age and non-Italian nationality were factors independently related to both HEV and HAV exposures. This data suggest the important role of low socio-economic factors in the transmission of both infections in high-risk populations. The possible epidemiological and/or pathogenetic links between HEV and HIV exposures need to be studied further.

Seroprevalence of antibodies and antigens against hepatitis A-E viruses in refugees and asylum seekers in Germany in 2015.

PubMed

Jablonka, Alexandra; Solbach, Philipp; Wöbse, Michael; Manns, Michael P; Schmidt, Reinhold E; Wedemeyer, Heiner; Cornberg, Markus; Behrens, Georg M N; Hardtke, Svenja

2017-08-01

Migration because of miscellaneous political crises in countries in the Middle East and Africa is a global challenge for whole Europe from an economic, social, and public health view. There is an urgent need to generate comprehensive, evidence-based data to expedite further screening and vaccination strategies. A total of 604 individuals ranging in age from 2 to 68 years who enrolled at a single reception center were tested for the prevalence of serologic markers for hepatitis virus types A, B, C, D, and E (HAV, HBV, HCV, HDV, HEV), respectively. Anti-HAV antibody prevalence was 91.2 and 70.3% in children younger than 18 years of age. The prevalence of anti-HEV antibodies was 20.1% among the individuals. 3.0% were positive for hepatitis B surface antigen, whereas 15.2% tested positive for anti-hepatitis B core antigen. None of the refugees tested positive for anti-HDV. 14.1% of refugees were vaccinated against hepatitis B and had a protective anti-hepatitis B surface level of at least 10 mIU/ml. Significant differences in vaccination status were found between the regions (Eastern Mediterranean Region with 77/482 (16.0%; 95% confidence interval=12.7-19.3%) versus African Region with 1/55 (1.8%; 95% confidence interval=0-5.0%). The prevalence of anti-HCV antibodies was 1.2% (n=7), with 0.7% HCV RNA positivity; 16.7% of hepatitis B surface antigen-positive individuals were HCV coinfected (n=3). The prevalence of refugees with previous exposure to hepatitis viruses was higher than that in the general German population, but lower than in other migrant populations in Germany. The vaccination status against hepatitis B was poor.

Microbial carbonylation and hydroxylation of 20(R)-panaxadiol by Aspergillus niger.

PubMed

Yan, Bin; Chen, Zhihua; Zhai, Xuguang; Yin, Guibo; Ai, Yafei; Chen, Guangtong

2018-04-01

20(R)-panaxadiol (PD) was metabolised by the fungus Aspergillus niger AS 3.3926 to its C-3 carbonylated metabolite and five other hydroxylated metabolites (1-6). Their structures were elucidated as 3-oxo-20(R)-panaxadiol (1), 3-oxo-7β-hydroxyl- 20(R)-panaxadiol (2), 3-oxo-7β,23α-dihydroxyl-20(R)-panaxadiol (3), 3,12-dioxo- 7β,23β-dihydroxyl-20(R)-panaxadiol (4), 3-oxo-1α,7β-dihydroxyl-20(R)-panaxadiol (5) and 3-oxo-7β,15β-dihydroxyl-20(R)-panaxadiol (6) by spectroscopic analysis. Among them, compounds 2-6 were new compounds. Pharmacological studies revealed that compound 6 exhibited significant anti-hepatic fibrosis activity.

Hemin potentiates the anti-hepatitis C virus activity of the antimalarial drug artemisinin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paeshuyse, Jan; Coelmont, Lotte; Vliegen, Inge

2006-09-15

We report that the antimalarial drug artemisinin inhibits hepatitis C virus (HCV) replicon replication in a dose-dependent manner in two replicon constructs at concentrations that have no effect on the proliferation of the exponentially growing host cells. The 50% effective concentration (EC{sub 5}) for inhibition of HCV subgenomic replicon replication in Huh 5-2 cells (luciferase assay) by artemisinin was 78 {+-} 21 {mu}M. Hemin, an iron donor, was recently reported to inhibit HCV replicon replication [mediated by inhibition of the viral polymerase (C. Fillebeen, A.M. Rivas-Estilla, M. Bisaillon, P. Ponka, M. Muckenthaler, M.W. Hentze, A.E. Koromilas, K. Pantopoulos, Iron inactivatesmore » the RNA polymerase NS5B and suppresses subgenomic replication of hepatitis C virus, J. Biol. Chem. 280 (2005) 9049-9057.)] at a concentration that had no adverse effect on the host cells. When combined, artemisinin and hemin resulted, over a broad concentration range, in a pronounced synergistic antiviral activity. Also at a concentration (2 {mu}M) that alone had no effect on HCV replication, hemin still potentiated the anti-HCV activity of artemisinin.« less

Antioxidant and Anti-Hepatitis C Viral Activities of Commercial Milk Thistle Food Supplements

PubMed Central

Anthony, Kevin; Subramanya, Gitanjali; Uprichard, Susan; Hammouda, Faiza; Saleh, Mahmoud

2013-01-01

Milk thistle dietary supplements that contain silymarin are widely marketed and used in the USA and other countries for liver enhancement and recovery. More recently, silymarin has also been identified as a possible antiviral for the treatment of hepatitis C virus (HCV) infection. To assess different brands of commercially sold silymarin, 45 products were collected from local stores and analyzed for their silymarin content, antioxidant activities, and antiviral activity against HCV. Antioxidant activity was measured as radical scavenging activity using DPPH and by estimating their antioxidant capacity as trolox equivalent. Anti-HCV activity was measured in an HCV genotype 1b replication inhibition assay. Samples were found to vary widely in their silymarin content, with some samples having none or very low concentrations while silymarin represented higher than 80% of other samples. Both antioxidant and anti-HCV activity correlated with the overall level of silymarin. PMID:26787620

[Anti-hepatitis B surface antigen titres in vaccinated dentistry students at Damascus University].

PubMed

Srour, I H; Mashlah, A

2012-06-01

Dental practice carries considerable danger for acquiring bloodborne pathogens such as hepatitis B virus (HBV). Vaccination against this virus is an important approach to reducing the infection. Post-vaccination test to confirm the seroconversion is important also. Over the period 1 March-31 May 2010, we assessed the efficacy of HBV vaccination among 91 fourth-year dental students at Damascus University, who were vaccinated under the mandatory Faculty of Dentistry programme. Anti-HBsAg antibody titres were determined in the blood samples using an enzyme immunoassay to measure; > or = 10 IU/mm was considered an adequate response titer. Seven of the 91 dentistry students (7.7%) had anti-HBs antibody titre < 10 mlU/mL. The frequency of unresponsiveness was significantly higherwith smoking (P = 0.012) and alcohol consumption (P = 0.014). Anti-HBs test should be included in routine immunization services of the School of Dentistry at Damascus University.

In vivo antiviral activity and pharmacokinetics of (-)-cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine in woodchuck hepatitis virus-infected woodchucks.

PubMed Central

Cullen, J M; Smith, S L; Davis, M G; Dunn, S E; Botteron, C; Cecchi, A; Linsey, D; Linzey, D; Frick, L; Paff, M T; Goulding, A; Biron, K

1997-01-01

The (-) enantiomer of cis-5-fluoro-1l-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine [(-)-FTC)], a substituted oxathiolane compound with anti-hepatitis B virus activity in vitro, was assessed for its efficacy in woodchucks with naturally acquired woodchuck hepatitis virus (WHV) infection. Pharmacokinetics and in vitro anabolism were also determined. (-)-FTC was anabolized to the 5'-triphosphate in a dose-related fashion, reaching a maximum concentration at about 24 h in cultured woodchuck hepatocytes. Following administration of a dose of 10 mg/kg of body weight intraperitoneally (i.p.), the clearance of (-)-FTC from plasma was monoexponential, the terminal half-life was 3.76 +/- 1.4 h, and the systemic clearance was 0.12 +/- 0.06 liters/h/kg. The antiviral efficacy of (-)-FTC in the woodchuck model was assessed by quantitation of serum WHV DNA levels and by WHV particle-associated DNA polymerase activity at two dosages, 30 and 20 mg/kg given i.p. twice daily (b.i.d.), respectively. The level of WHV DNA in serum was reduced 20- to 150-fold (average, 56-fold) in the 30-mg/kg-b.i.d. treatment group and 6- to 49-fold (average, 27-fold) in the 20-mg/kg-b.i.d. treatment group. Viral DNA polymerase levels diminished accordingly. One week after treatment was discontinued, WHV levels returned to pretreatment levels in both studies. These animals were biopsied before and following treatment with 30 mg of (-)-FTC per kg. Their livers were characterized by a mild increase in cytoplasmic lipid levels, but this change was not associated with altered liver enzyme levels. Serum chemistry and hematology results were within the normal ranges for all treated animals. We conclude that (-)-FTC is a potent antihepadnaviral agent and that it has no detectable toxic effects in woodchucks when given for up to 25 days. Further development of (-)-FTC as an anti-hepatitis B virus therapy for patients is warranted. PMID:9333028

Acute liver failure caused by hepatitis E virus genotype 3 and 4: A systematic review and pooled analysis.

PubMed

Haffar, Samir; Shalimar; Kaur, Ravinder J; Wang, Zhen; Prokop, Larry J; Murad, Mohammad H; Bazerbachi, Fateh

2018-04-19

Acute liver failure caused by hepatitis E virus genotype 3 and 4 has been rarely described. Because of the presence of a short golden therapeutic window in patients with viral acute liver failure from other causes, it is possible that early recognition and treatment might reduce the morbidity and mortality. We performed a systematic review and pooled analysis of acute liver failure caused by hepatitis E virus genotype 3 and 4. Two reviewers appraised studies after searching multiple databases on June 12th, 2017. Appropriate tests were used to compare hepatitis E virus genotype 3 vs 4, suspected vs confirmed genotypes, hepatitis E virus-RNA positive vs negative, and to discern important mortality risk factors. We identified 65 patients, with median age 58 years (range: 3-79), and a male to female ratio of 1.2:1. The median bilirubin, ALT, AST and alkaline phosphatase (expressed by multiplication of the upper limit of normal) levels were 14.8, 45.3, 34.8 and 1.63 respectively. Antihepatitis E virus IgG, antihepatitis E virus IgM and hepatitis E virus-RNA were positive in 84%, 91% and 86% of patients respectively. The median interval from symptoms onset to acute liver failure was 23 days, and 16 patients underwent liver transplantation. Final outcome was reported in 58 patients and mortality was 46%. Age was a predictor of poor prognosis in multivariate analysis. No important differences were found between patients infected with genotype 3 vs 4, patients with confirmed vs suspected genotypes, or patients with positive vs negative RNA. Acute liver failure caused by hepatitis E virus genotype 3 and 4 is rare, similar between genotypes, occurs commonly in middle-aged/elderly patients and has a very high mortality. Age is predictive of poor prognosis in multivariate analysis. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hepatitis E seroprevalence in the Americas: A systematic review and meta-analysis.

PubMed

Horvatits, Thomas; Ozga, Ann-Kathrin; Westhölter, Dirk; Hartl, Johannes; Manthey, Carolin F; Lütgehetmann, Marc; Rauch, Geraldine; Kriston, Levente; Lohse, Ansgar W; Bendall, Richard; Wedemeyer, Heiner; Dalton, Harry R; Pischke, Sven

2018-04-16

While hepatitis E virus infections are a relevant topic in Europe, knowledge about epidemiology of hepatitis E virus infections in the USA and Latin America is still limited. Aim of this study was to estimate anti-hepatitis E virus IgG seroprevalence in the Americas and to assess whether low socioeconomic status is associated with hepatitis E virus exposure. We performed a systematic review and meta-analysis. Literature search was performed in PubMed for articles published 01/1994-12/2016. Prevalence was estimated using a mixed-effects model and reported in line with PRISMA reporting guidelines. Seroprevalence was significantly higher in the USA than in Latin America, independently of assay, patient cohort, methodological quality or study year (OR: 1.82 (1.06-3.08), P = .03). Patients in the USA had a more than doubled estimated seroprevalence (up to 9%, confidence interval 5%-15.6%) than those in Brazil (up to 4.2%, confidence interval 2.4%-7.1%; OR: 2.27 (1.25-4.13); P = .007) and Mixed Caribbean (up to 1%, OR: 8.33 (1.15-81.61); P = .04). A comparison with published data from Europe demonstrated that anti-hepatitis E virus seroprevalence in the USA and Europe did not differ significantly (OR: 1.33 (0.81-2.19), P = .25), while rate in South America was significantly lower than that in Europe (OR: 0.67 (0.45-0.98), P = .04). Hepatitis E virus is common in the USA. Surprisingly, the risk of hepatitis E virus exposure was low in many South American countries. Seroprevalence did not differ significantly between Europe and the USA. Hence, hepatitis E virus is not limited to countries with low sanitary standards, and a higher socioeconomic status does not protect populations from hepatitis E virus exposure. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Spanish human papillomavirus vaccine consensus group: a working model.

PubMed

Cortés-Bordoy, Javier; Martinón-Torres, Federico

2010-08-01

Successful implementation of Human Papillomavirus (HPV) vaccine in each country can only be achieved from a complementary and synergistic perspective, integrating all the different points of view of the diverse related professionals. It is this context where the Spanish HPV Vaccine Consensus Group (Grupo Español de Consenso sobre la Vacuna VPH, GEC-VPH) was created. GEC-VPH philosophy, objectives and experience are reported in this article, with particular attention to the management of negative publicity and anti-vaccine groups. Initiatives as GEC-VPH--adapted to each country's particular idiosyncrasies--might help to overcome the existing barriers and to achieve wide and early implementation of HPV vaccination.

The effect of prior transfusion history on blood donor anti-hepatitis C virus antibody.

PubMed

Mazda, T; Nakata, K; Ota, K; Kaminuma, Y; Katayama, T

1993-01-01

In Japan, the major transfusion-associated disease is non-A, non-B hepatitis. We studied the relationship between transfusion history and blood donor antibodies to hepatitis C virus (HCV). The positive rate of antibodies to the HCV nonstructural protein (c100-3) depended on age and the time elapsed since transfusion. The anti-c100-3 ratio for subjects with transfusions made prior to 20 years ago was high. One quarter century ago, a change occurred in national blood policy from paid to non-paid voluntary donations. We also have studied the anti-HCV positive rate among donors with prior transfusion using a second generation HCV test kit which includes anti-HCV core antibody detection. The anti-HCV positive rate for the second generation test was higher than that for the anti-c100-3 test. Introduction of the second generation test is therefore more useful in screening than the anti-c100-3 test for blood programs.

[Infinite metamorphosis: witches, spirits and apuntes in Havana].

PubMed

Cunha, Olívia Maria Gomes da

2015-01-01

This article offers an alternative reading of Hampa afro-cubana: los negros brujos, by the Cuban Fernando Ortiz y Fernandes, and discusses the need to make the different ideas expounded by the author more complex. For this reason, it disputes the interpretations of some commentators influenced by his work. The article suggests some clues with regard to what Ortiz y Fernandes understood as forces capable of acting and manifesting themselves in the "bodies" of persons affected by the activities of those accused of being involved with magical practices and objects. It examines the creation of witches - as described by Ortiz y Fernandes - as an epistemic phenomenon and discusses the arguments and the practices and knowledge required for this purpose.

An anti-HBV anthraquinone from aciduric fungus Penicillium sp. OUCMDZ-4736 under low pH stress.

PubMed

Jin, Yanzheng; Qin, Shidong; Gao, Hai; Zhu, Guoliang; Wang, Wei; Zhu, Weiming; Wang, Yi

2018-01-01

To obtain new bioactive natural products, the effect of acidic stress on the metabolites of an aciduric fungus was investigated. This fungus, Penicillium sp. OUCMDZ-4736, which was isolated from the sediment around roots of mangrove (Acanthus ilicifolius), produced different compounds and higher yields under pH 2.5 than under neutral conditions. Using spectroscopic analyses and calculations, three new anthraquinone derivatives (1-3) were isolated and identified from the acidic fermentation broth (pH 2.5) of OUCMDZ-4736. Compound 1 showed much stronger anti-hepatitis B virus activity than that of the positive control, lamivudine, strongly inhibiting HBsAg and HBeAg secretion from HepG2.2.15 cells. These results show that extremophiles are a valuable resource of bioactive compounds, and that pH regulation is an effective strategy to induce metabolite production in aciduric fungi.

Antimicrobial susceptibilities and capsular types of invasive Streptococcus pneumoniae isolated in children in Mexico City.

PubMed

Echániz-Aviles, G; Velázquez-Meza, M E; Carnalla-Barajas, M N; Soto-Noguerón, A; Solórzano-Santos, F; Pérez Miravete, A; Gatica-Marquina, R; di Fabio, J L

1997-01-01

As part of the Sistema Regional de Vacunas (SIREVA) initiative, we conducted a surveillance study to determine the relative prevalence of capsular types of Streptococcus pneumoniae and antimicrobial susceptibility of invasive isolates in children less than 5 years old. We collected 220 isolates and found 33 of the 90 known types, with type 23F as the most common followed by types 6A+B, 14, 19F, and 19A. High penicillin resistance was found in 49 strains (22.2%), 31 belonging to type 23F. Twenty-nine (13.1%) were resistant to erythromycin, 95 (43.1%) were resistant to chloramphenicol, and 24 (10.9%) were resistant to cefotaxime. No strains were resistant to vancomycin.

Viral hepatitis as an occupational disease in Poland.

PubMed

Bilski, Bartosz

2011-07-01

involved in reducing the number of cases of occupational viral hepatitis. Socioeconomic and financial factors affected the epidemiological data on cases of hepatitis certified as an occupational disease in Poland. An additional problem associated with the diagnosis of occupational diseases is the lack of obligatory testing for anti-hepatitis C virus (HCV) and anti-hepatitis B surface antigen (HBsAg) antibodies and examinations to ensure the efficacy of HBV vaccination among medical staff before and during employment.

Biochemical Characterization of Human Anti-Hepatitis B Monoclonal Antibody Produced in the Microalgae Phaeodactylum tricornutum.

PubMed

Vanier, Gaëtan; Hempel, Franziska; Chan, Philippe; Rodamer, Michael; Vaudry, David; Maier, Uwe G; Lerouge, Patrice; Bardor, Muriel

2015-01-01

Monoclonal antibodies (mAbs) represent actually the major class of biopharmaceuticals. They are produced recombinantly using living cells as biofactories. Among the different expression systems currently available, microalgae represent an emerging alternative which displays several biotechnological advantages. Indeed, microalgae are classified as generally recognized as safe organisms and can be grown easily in bioreactors with high growth rates similarly to CHO cells. Moreover, microalgae exhibit a phototrophic lifestyle involving low production costs as protein expression is fueled by photosynthesis. However, questions remain to be solved before any industrial production of algae-made biopharmaceuticals. Among them, protein heterogeneity as well as protein post-translational modifications need to be evaluated. Especially, N-glycosylation acquired by the secreted recombinant proteins is of major concern since most of the biopharmaceuticals including mAbs are N-glycosylated and it is well recognized that glycosylation represent one of their critical quality attribute. In this paper, we assess the quality of the first recombinant algae-made mAbs produced in the diatom, Phaeodactylum tricornutum. We are focusing on the characterization of their C- and N-terminal extremities, their signal peptide cleavage and their post-translational modifications including N-glycosylation macro- and microheterogeneity. This study brings understanding on diatom cellular biology, especially secretion and intracellular trafficking of proteins. Overall, it reinforces the positioning of P. tricornutum as an emerging host for the production of biopharmaceuticals and prove that P. tricornutum is suitable for producing recombinant proteins bearing high mannose-type N-glycans.

Anti-hepatitis C virus activity and toxicity of type III phosphatidylinositol-4-kinase beta inhibitors.

PubMed

Lamarche, M J; Borawski, J; Bose, A; Capacci-Daniel, C; Colvin, R; Dennehy, M; Ding, J; Dobler, M; Drumm, J; Gaither, L A; Gao, J; Jiang, X; Lin, K; McKeever, U; Puyang, X; Raman, P; Thohan, S; Tommasi, R; Wagner, K; Xiong, X; Zabawa, T; Zhu, S; Wiedmann, B

2012-10-01

Type III phosphatidylinositol-4-kinase beta (PI4KIIIβ) was previously implicated in hepatitis C virus (HCV) replication by small interfering RNA (siRNA) depletion and was therefore proposed as a novel cellular target for the treatment of hepatitis C. Medicinal chemistry efforts identified highly selective PI4KIIIβ inhibitors that potently inhibited the replication of genotype 1a and 1b HCV replicons and genotype 2a virus in vitro. Replicon cells required more than 5 weeks to reach low levels of 3- to 5-fold resistance, suggesting a high resistance barrier to these cellular targets. Extensive in vitro profiling of the compounds revealed a role of PI4KIIIβ in lymphocyte proliferation. Previously proposed functions of PI4KIIIβ in insulin secretion and the regulation of several ion channels were not perturbed with these inhibitors. Moreover, PI4KIIIβ inhibitors were not generally cytotoxic as demonstrated across hundreds of cell lines and primary cells. However, an unexpected antiproliferative effect in lymphocytes precluded their further development for the treatment of hepatitis C.

Anti-Hepatitis C Virus Activity and Toxicity of Type III Phosphatidylinositol-4-Kinase Beta Inhibitors

PubMed Central

LaMarche, M. J.; Borawski, J.; Bose, A.; Capacci-Daniel, C.; Colvin, R.; Dennehy, M.; Ding, J.; Dobler, M.; Drumm, J.; Gaither, L. A.; Gao, J.; Jiang, X.; Lin, K.; McKeever, U.; Puyang, X.; Raman, P.; Thohan, S.; Tommasi, R.; Wagner, K.; Xiong, X.; Zabawa, T.; Zhu, S.

2012-01-01

Type III phosphatidylinositol-4-kinase beta (PI4KIIIβ) was previously implicated in hepatitis C virus (HCV) replication by small interfering RNA (siRNA) depletion and was therefore proposed as a novel cellular target for the treatment of hepatitis C. Medicinal chemistry efforts identified highly selective PI4KIIIβ inhibitors that potently inhibited the replication of genotype 1a and 1b HCV replicons and genotype 2a virus in vitro. Replicon cells required more than 5 weeks to reach low levels of 3- to 5-fold resistance, suggesting a high resistance barrier to these cellular targets. Extensive in vitro profiling of the compounds revealed a role of PI4KIIIβ in lymphocyte proliferation. Previously proposed functions of PI4KIIIβ in insulin secretion and the regulation of several ion channels were not perturbed with these inhibitors. Moreover, PI4KIIIβ inhibitors were not generally cytotoxic as demonstrated across hundreds of cell lines and primary cells. However, an unexpected antiproliferative effect in lymphocytes precluded their further development for the treatment of hepatitis C. PMID:22825118

Cynaropicrin: A Comprehensive Research Review and Therapeutic Potential As an Anti-Hepatitis C Virus Agent

PubMed Central

Elsebai, Mahmoud F.; Mocan, Andrei; Atanasov, Atanas G.

2016-01-01

The different pharmacologic properties of plants-containing cynaropicrin, especially artichokes, have been known for many centuries. More recently, cynaropicrin exhibited a potential activity against all genotypes of hepatitis C virus (HCV). Cynaropicrin has also shown a wide range of other pharmacologic properties such as anti-hyperlipidemic, anti-trypanosomal, anti-malarial, antifeedant, antispasmodic, anti-photoaging, and anti-tumor action, as well as activation of bitter sensory receptors, and anti-inflammatory properties (e.g., associated with the suppression of the key pro-inflammatory NF-κB pathway). These pharmacological effects are very supportive factors to its outstanding activity against HCV. Structurally, cynaropicrin might be considered as a potential drug candidate, since it has no violations for the rule of five and its water-solubility could allow formulation as therapeutic injections. Moreover, cynaropicrin is a small molecule that can be easily synthesized and as the major constituent of the edible plant artichoke, which has a history of safe dietary use. In summary, cynaropicrin is a promising bioactive natural product that, with minor hit-to-lead optimization, might be developed as a drug for HCV. PMID:28008316

Anti-hepatitis C virus seroprevalence in the working age population in Poland, 2004 to 2014

PubMed Central

Walewska-Zielecka, Bożena; Religioni, Urszula; Juszczyk, Grzegorz; Wawrzyniak, Zbigniew M; Czerw, Aleksandra; Soszyński, Piotr; Fronczak, Adam

2017-01-01

Hepatitis C virus (HCV) infection is considered by the World Health Organization (WHO) to be a serious public health concern and one of the major public health priorities. In 2005, it was estimated that there are 185 million anti-HCV positive people in the world, which constitutes 2.8% of the global population. Our study estimates the anti-HCV seroprevalence in the working age population (15–64 years-old), mostly urban and suburban residents, in Poland from 2004 to 2014. The studied group consisted of 61,805 working-age population representatives whose data were obtained from electronic medical records of an outpatient clinic network operating on a countrywide level. Positive anti-HCV test results were obtained in 957 patients, representing 1.5% of the whole population studied throughout the analysed period. The average age of all anti-HCV positive patients was 36.8 years. Analysis of the data suggests that the proportion of anti-HCV positive patients decreased over the study period (mean positive anti-HCV = -0.0017 × year + 3.3715; R2 = 0.7558). In 2004, positive results were noted among 3.2% of patients undergoing HCV antibody tests, but in 2014, the percentage of patients with a positive result stood at 1.1%. The apparent decrease affected men and women similarly. Our study also provides evidence that screening people born before 1965 could be beneficial. PMID:28106526

Evaluation of an immunochromatographic assay for the detection of anti-hepatitis A virus IgM

PubMed Central

2010-01-01

Background Hepatitis A virus (HAV) is a causative agent of acute hepatitis, which is transmitted by person-to-person contact and via the faecal-oral route. Acute HAV infection is usually confirmed by anti-HAV IgM detection. In order to detect anti-HAV IgM in the serum of patients infected with HAV, we developed a rapid assay based on immunochromatography (ICA) and evaluated the sensitivity of this assay by comparing it with a commercial microparticle enzyme immunoassay (MEIA) that is widely used for serological diagnosis. Results The newly developed ICA showed 100% sensitivity and specificity when used to test 150 anti-HAV IgM-positive sera collected from infected patients and 75 negative sera from healthy subjects. Also, the sensitivity of ICA is about 10 times higher than MEIA used in this study by determining end point to detect independent on infected genotype of HAV. In addition, the ICA was able to detect 1 positive sample from among 50 sera from acute hepatitis patients that had tested negative for anti-HAV IgM using the MEIA. Conclusion Conclusively, ICA for the detection of anti-HAV IgM will be very effective for rapid assay to apply clinical diagnosis and epidemiological investigation on epidemics due to the simplicity, rapidity and specificity. PMID:20637129

Long term persistence of anti-HBs protective levels in young patients with type 1 diabetes after recombinant hepatitis B vaccine.

PubMed

Marseglia, G; Alibrandi, A; d'Annunzio, G; Gulminetti, R; Avanzini, M A; Marconi, M; Tinelli, C; Lorini, R

2000-11-22

The aim of the present study was to evaluate the persistence of anti-hepatitis B protective levels in young patients with type 1 diabetes, successfully immunised with a recombinant hepatitis B vaccine. We re-evaluated, after a 4 year follow-up, 54 patients and 70 age and sex-matched healthy subjects. Protective antibodies levels were found in 50/54 (92%) patients and in 67/70 (96%) controls. Moreover, anti-HBs levels were similar in diabetic patients and controls (means of log-titre and (sd); 1.95 (0.88) and 2.18 (0.64) patients and controls, respectively; P=0.11). No cases of clinical hepatitis were reported and all patients and controls remained HBc negative. These data demonstrate the persistence of anti-HBs levels in children, adolescents and young patients with type 1 diabetes after recombinant hepatitis B vaccine showing evidence of longterm immunogenity and protective effect.

Design of a sedimentation hole in a microfluidic channel to remove blood cells from diluted whole blood

NASA Astrophysics Data System (ADS)

Kuroda, Chiaki; Ohki, Yoshimichi; Ashiba, Hiroki; Fujimaki, Makoto; Awazu, Koichi; Makishima, Makoto

2017-03-01

With the aim of developing a sensor for rapidly detecting viruses in a drop of blood, in this study, we analyze the shape of a hole in a microfluidic channel in relation to the efficiency of sedimentation of blood cells. The efficiency of sedimentation is examined on the basis of our calculation and experimental results for two types of sedimentation hole, cylindrical and truncated conical holes, focusing on the Boycott effect, which can promote the sedimentation of blood cells from a downward-facing wall. As a result, we demonstrated that blood cells can be eliminated with an efficiency of 99% or higher by retaining a diluted blood sample of about 30 µL in the conical hole for only 2 min. Moreover, we succeeded in detecting the anti-hepatitis B surface antigen antibody in blood using a waveguide-mode sensor equipped with a microfluidic channel having the conical sedimentation hole.

Silent killers: Transfusion Transmissible Infections-TTI, among asymptomatic population of Pakistan.

PubMed

Saeed, Muhammad; Hussain, Shahida; Rasheed, Farhan; Ahmad, Maqsood; Arif, Mizna; Hamid Rahmani, Muhammad Tariq

2017-03-01

To analyse transfusion transmissible infections in asymptomatic population. This study was conducted at the Allama Iqbal Medical College and Jinnah Hospital, Lahore, Pakistan, from December 2014 to November 2015, and comprised healthy asymptomatic blood donors.Every sample was screened for the presence of antibodies/antigens of hepatitis C virus, human immunodeficiency virus, treponemapallidum, hepatitis B virus and malaria parasite through rapid immunochromatographic technique. Of the 18,274 blood donors, 17,276(94.53%) were found healthy and 998(5.46%) were infected. Besides, 71(0.38%) had multiple infections. The overall frequency of anti-hepatitis C virus, treponemapallidum (syphilis), hepatitis B surface antigen, malaria parasite and anti-human immunodeficiency virus was 480(2.62%), 284(1.55%), 210(1.10%), 20(0.10%) and 4(0.02%), respectively. Blood transfusion was found to be a significant but preventable mode of spread of transfusion transmissible infections.

Salmonella Fecal Shedding and Immune Responses are Dose- and Serotype- Dependent in Pigs

PubMed Central

Ivanek, Renata; Österberg, Julia; Gautam, Raju; Sternberg Lewerin, Susanna

2012-01-01

Despite the public health importance of Salmonella infection in pigs, little is known about the associated dynamics of fecal shedding and immunity. In this study, we investigated the transitions of pigs through the states of Salmonella fecal shedding and immune response post-Salmonella inoculation as affected by the challenge dose and serotype. Continuous-time multistate Markov models were developed using published experimental data. The model for shedding had four transient states, of which two were shedding (continuous and intermittent shedding) and two non-shedding (latency and intermittent non-shedding), and one absorbing state representing permanent cessation of shedding. The immune response model had two transient states representing responses below and above the seroconversion level. The effects of two doses [low (0.65×106 CFU/pig) and high (0.65×109 CFU/pig)] and four serotypes (Salmonella Yoruba, Salmonella Cubana, Salmonella Typhimurium, and Salmonella Derby) on the models' transition intensities were evaluated using a proportional intensities model. Results indicated statistically significant effects of the challenge dose and serotype on the dynamics of shedding and immune response. The time spent in the specific states was also estimated. Continuous shedding was on average 10–26 days longer, while intermittent non-shedding was 2–4 days shorter, in pigs challenged with the high compared to low dose. Interestingly, among pigs challenged with the high dose, the continuous and intermittent shedding states were on average up to 10–17 and 3–4 days longer, respectively, in pigs infected with S. Cubana compared to the other three serotypes. Pigs challenged with the high dose of S. Typhimurium or S. Derby seroconverted on average up to 8–11 days faster compared to the low dose. These findings highlight that Salmonella fecal shedding and immune response following Salmonella challenge are dose- and serotype-dependent and that the detection of specific

An outbreak of hepatitis A associated with a bakery, New York, 1994: the 1968 "West Branch, Michigan' outbreak repeated.

PubMed Central

Weltman, A. C.; Bennett, N. M.; Ackman, D. A.; Misage, J. H.; Campana, J. J.; Fine, L. S.; Doniger, A. S.; Balzano, G. J.; Birkhead, G. S.

1996-01-01

In a community hepatitis A outbreak in the Rochester, New York area, 64 of 79 (81%) people with anti-hepatitis A IgM-antibodies and onset of symptoms from 9 April-31 May 1994, recalled eating food obtained from a retail buyer's club. Eleven (65%) of 17 households with cases contained club members compared with 7 (21%) of 34 neighbourhood-matched control-households (matched odds ratio 8.5; 95% CI 1.7-41.6). Club employees who ate sugar-glazed baked goods were at fourfold increased risk for hepatitis. The source of infection was an IgM-positive baker who contaminated baked goods while applying sugar glaze. Computer-generated purchase lists implicated 11-12 March and 21-24 March as the most likely dates when contamination occurred. This investigation demonstrates the importance of food workers adhering to established hygiene practices. Computer-generated commercial datasets can be useful in epidemiologic investigations. PMID:8870631

Exploring the concurrent presence of hepatitis A virus genome in serum, stool, saliva, and urine samples of hepatitis A patients.

PubMed

Joshi, Madhuri S; Bhalla, Shilpa; Kalrao, Vijay R; Dhongade, Ramchandra K; Chitambar, Shobha D

2014-04-01

The use of saliva and urine as an alternative to serum samples for detection of anti-hepatitis A virus (HAV) IgM antibodies has been documented. However, these samples remain underreported or unexplored for shedding of HAV. To address this issue, paired serum, stool, saliva, and urine samples collected from hepatitis A patients were screened by reverse transcription polymerase chain reaction for detection of HAV RNA. HAV RNA was detected in 67.6% (44/65), 52.3% (34/65), 8.7% (5/57), and 12.3% (8/65) of the serum, stool, saliva, and urine samples, respectively. Phylogenetic analysis of nucleotide sequences obtained for partial RNA polymerase region grouped HAV strains from all of the clinical samples of the study in subgenotype IIIA. Low frequency of HAV nucleic acid in saliva and urine samples indicates limited utility of these samples in genomic studies on HAV but suggests its potential for transmission and infection of hepatitis A. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed

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

2015-08-28

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

First evaluation of the serum level of anti-hepatitis B surface antigen after vaccination in Libya.

PubMed

Madour, A; Alkout, A; Vanin, S

2013-12-01

The hepatitis B virus (HBV) vaccination schedule in Libya follows international recommendations (1st dose at birth, 2nd after 1 month and 3rd after 6 months). This research aimed to evaluate the long-term protection of the HBV immunization programme in Tripoli and to determine the best age to administer booster doses. Serum levels of hepatitis B surface antigen were determined in 277 randomly selected children aged 1-12 years. The response to HBV vaccine in 1-3-year-olds was 93.2%, but this declined with age and at 7-9 years after initial vaccination only 53.1% of children had protective titres (> or = 10 mIU/mL). No significant differences between males and females in antibody persistence or response to vaccine were observed. We recommend continuing the HBV vaccination programme and that a booster dose be given to 6-year-old children to ensure maximum protection during the period of school entry and beyond.

Identification of cellular and viral factors related to anti-hepatitis C virus activity of cyclophilin inhibitor.

PubMed

Goto, Kaku; Watashi, Koichi; Inoue, Daisuke; Hijikata, Makoto; Shimotohno, Kunitada

2009-10-01

We have so far reported that an immunosuppressant cyclosporin A (CsA), a well-known cyclophilin (CyP) inhibitor (CPI), strongly suppressed hepatitis C virus (HCV) replication in cell culture, and that CyPB was a cellular cofactor for viral replication. To further investigate antiviral mechanisms of CPI, we here developed cells carrying CsA-resistant HCV replicons, by culturing the HCV subgenomic replicon cells for 4 weeks in the presence of CsA with G418. Transfection of total RNA from the isolated CsA-resistant cells to naïve Huh7 cells conferred CsA resistance, suggesting that the replicon RNA itself was responsible for the resistant phenotype. Of the identified amino acid mutations, D320E in NS5A conferred the CsA resistance. The replicon carrying the D320E mutation was sensitive to interferon-alpha, but was resistant to CsA and other CPIs including NIM811 and sanglifehrin A. Knockdown of individual CyP subtypes revealed CyP40, in addition to CyPA and CyPB, contributed to viral replication, and CsA-resistant replicons acquired independence from CyPA for efficient replication. These data provide important evidence on the mechanisms underlying the regulation of HCV replication by CyP and for designing novel and specific anti-HCV strategies with CPIs.

Single-Genome Sequencing of Hepatitis C Virus in Donor-Recipient Pairs Distinguishes Modes and Models of Virus Transmission and Early Diversification.

PubMed

Li, Hui; Stoddard, Mark B; Wang, Shuyi; Giorgi, Elena E; Blair, Lily M; Learn, Gerald H; Hahn, Beatrice H; Alter, Harvey J; Busch, Michael P; Fierer, Daniel S; Ribeiro, Ruy M; Perelson, Alan S; Bhattacharya, Tanmoy; Shaw, George M

2016-01-01

Despite the recent development of highly effective anti-hepatitis C virus (HCV) drugs, the global burden of this pathogen remains immense. Control or eradication of HCV will likely require the broad application of antiviral drugs and development of an effective vaccine. A precise molecular identification of transmitted/founder (T/F) HCV genomes that lead to productive clinical infection could play a critical role in vaccine research, as it has for HIV-1. However, the replication schema of these two RNA viruses differ substantially, as do viral responses to innate and adaptive host defenses. These differences raise questions as to the certainty of T/F HCV genome inferences, particularly in cases where multiple closely related sequence lineages have been observed. To clarify these issues and distinguish between competing models of early HCV diversification, we examined seven cases of acute HCV infection in humans and chimpanzees, including three examples of virus transmission between linked donors and recipients. Using single-genome sequencing (SGS) of plasma vRNA, we found that inferred T/F sequences in recipients were identical to viral sequences in their respective donors. Early in infection, HCV genomes generally evolved according to a simple model of random evolution where the coalescent corresponded to the T/F sequence. Closely related sequence lineages could be explained by high multiplicity infection from a donor whose viral sequences had undergone a pretransmission bottleneck due to treatment, immune selection, or recent infection. These findings validate SGS, together with mathematical modeling and phylogenetic analysis, as a novel strategy to infer T/F HCV genome sequences. Despite the recent development of highly effective, interferon-sparing anti-hepatitis C virus (HCV) drugs, the global burden of this pathogen remains immense. Control or eradication of HCV will likely require the broad application of antiviral drugs and the development of an effective

Rethinking the old antiviral drug moroxydine: Discovery of novel analogues as anti-hepatitis C virus (HCV) agents.

PubMed

Magri, Andrea; Reilly, Roisin; Scalacci, Nicolò; Radi, Marco; Hunter, Michael; Ripoll, Manon; Patel, Arvind H; Castagnolo, Daniele

2015-11-15

The discovery of a novel class of HCV inhibitors is described. The new amidinourea compounds were designed as isosteric analogues of the antiviral drug moroxydine. The two derivatives 11g and 11h showed excellent HCV inhibition activity and viability and proved to inhibit a step(s) of the RNA replication. The new compounds have been synthesized in only three synthetic steps from cheap building blocks and in high yields, thus turning to be promising drug candidates in the development of cheaper HCV treatments. Copyright © 2015 Elsevier Ltd. All rights reserved.

Immunizations with chimeric hepatitis B virus-like particles to induce potential anti-hepatitis C virus neutralizing antibodies.

PubMed

Vietheer, Patricia T K; Boo, Irene; Drummer, Heidi E; Netter, Hans-Jürgen

2007-01-01

Virus-like particles (VLPs) are highly immunogenic and proven to induce protective immunity. The small surface antigen (HBsAg-S) of hepatitis B virus (HBV) self-assembles into VLPs and its use as a vaccine results in protective antiviral immunity against HBV infections. Chimeric HBsAg-S proteins carrying foreign epitopes allow particle formation and have the ability to induce anti-foreign humoral and cellular immune responses. The insertion of the hypervariable region 1 (HVR1) sequence derived from the envelope protein 2 (E2) of hepatitis C virus (HCV) into the major antigenic site of HBsAg-S ('a'-determinant) resulted in the formation of highly immunogenic VLPs that retained the antigenicity of the inserted HVR1 sequence. BALB/c mice were immunized with chimeric VLPs, which resulted in antisera with anti-HCV activity. The antisera were able to immunoprecipitate native HCV envelope complexes (E1E2) containing homologous or heterologous HVR1 sequences. HCV E1E2 pseudotyped HIV-1 particles (HCVpp) were used to measure entry into HuH-7 target cells in the presence or absence of antisera that were raised against chimeric VLPs. Anti-HVR1 VLP sera interfered with entry of entry-competent HCVpps containing either homologous or heterologous HVR1 sequences. Also, immunizations with chimeric VLPs induced antisurface antigen (HBsAg) antibodies, indicating that HBV-specific antigenicity and immunogenicity of the 'a'-determinant region is retained. A multivalent vaccine against different pathogens based on the HBsAg delivery platform should be possible. We hypothesize that custom design of VLPs with an appropriate set of HCV-neutralizing epitopes will induce antibodies that would serve to decrease the viral load at the initial infecting inoculum.

Dimeric Matrine-Type Alkaloids from the Roots of Sophora flavescens and Their Anti-Hepatitis B Virus Activities.

PubMed

Zhang, Yu-Bo; Zhan, Li-Qin; Li, Guo-Qiang; Wang, Feng; Wang, Ying; Li, Yao-Lan; Ye, Wen-Cai; Wang, Guo-Cai

2016-08-05

Six unusual matrine-type alkaloid dimers, flavesines A-F (1-6, respectively), together with three proposed biosynthetic intermediates (7-9) were isolated from the roots of Sophora flavescens. Compounds 1-5 were the first natural matrine-type alkaloid dimers, and compound 6 represented an unprecedented dimerization pattern constructed by matrine and (-)-cytisine. Their structures were elucidated by NMR, MS, single-crystal X-ray diffraction, and a chemical method. The hypothetical biogenetic pathways of 1-6 were also proposed. Compounds 1-9 exhibited inhibitory activities against hepatitis B virus.

Physics Studies at the University of Havana

NASA Astrophysics Data System (ADS)

de Melo Pereira, Osvaldo; Sánchez Colina, María

The licenciatura en física degree course was created as part of the 1962 University Reform. It started at the Physics School within the Science Faculty of the University of Havana, also including the Schools of Mathematics, Chemistry, Biological Sciences, Geography and Psychology (Henriques Rodríguez, Daisy, R, Revista Cubana de Educación Superior XXI(8), 2001). The degree of licenciado had replaced that of baciller since 1880, but only the physico-mathematical sciences and physico-chemical sciences degree courses existed prior to the 1962 university reform. In this paper, we will analyze some data concerning the undergraduate and graduate studies during the 46 years elapsed since the creation of the physics degree course at the University of Havana. Several related issues, such as the development of scientific research and the influence of international collaboration, are dealt with in other contributions to this volume.

Helicobacter cinaedi bacteremia with cellulitis after ABO-incompatible living-donor liver transplantation: Case report.

PubMed

Mishima, Kohei; Obara, Hideaki; Sugita, Kayoko; Shinoda, Masahiro; Kitago, Minoru; Abe, Yuta; Hibi, Taizo; Yagi, Hiroshi; Matsubara, Kentaro; Mori, Takehiko; Takano, Yaoko; Fujiwara, Hiroshi; Itano, Osamu; Hasegawa, Naoki; Iwata, Satoshi; Kitagawa, Yuko

2015-07-07

Helicobacter cinaedi (H. cinaedi), a Gram-negative spiral-shaped bacterium, is an enterohepatic non-Helicobacter pylori Helicobacter species. We report the first case of H. cinaedi bacteremia with cellulitis after liver transplantation. A 48-year-old male, who had been a dog breeder for 15 years, underwent ABO-incompatible living-donor liver transplantation for hepatitis C virus-induced decompensated cirrhosis using an anti-hepatitis B core antibody-positive graft. The patient was preoperatively administered rituximab and underwent plasma exchange twice to overcome blood type incompatibility. After discharge, he had been doing well with immunosuppression therapy comprising cyclosporine, mycophenolate mofetil, and steroid according to the ABO-incompatible protocol of our institution. However, 7 mo after transplantation, he was admitted to our hospital with a diagnosis of recurrent cellulitis on the left lower extremity, and H. cinaedi was detected by both blood culture and polymerase chain reaction analysis. Antibiotics improved his symptoms, and he was discharged at day 30 after admission. Clinicians should be more aware of H. cinaedi in immunocompromised patients, such as ABO-incompatible transplant recipients.

Prevalence of human immunodeficiency virus, syphilis, hepatitis B and C in blood donations in Namibia.

PubMed

Mavenyengwa, Rooyen T; Mukesi, Munyaradzi; Chipare, Israel; Shoombe, Esra

2014-05-05

Transfusion Transmissible Infections (TTIs) such as Human Immunodeficiency Virus (HIV), syphilis, hepatitis B virus (HBV) and hepatitis C virus (HCV) are infections which are common in some communities in Southern Africa. It is important to screen blood donations for these infections. This is a retrospective study which involved reviewing of previous blood donation records for the year 2012 in Namibia. The records were analyzed to determine the prevalence of HIV, syphilis, Hepatitis B and C among blood donations with regard to gender, age and geographical region of the donors. The findings indicated a significantly low prevalence of HIV, syphilis, HBsAg and anti-Hepatitis C among the blood donations. A low infection rate of 1.3% by any of the four tested TTIs was found among the blood donations given by the donor population in Namibia in 2012. The blood donations given by the donor population in Namibia has a low infection rate with the HIV, syphilis, HBsAg and anti-HCV. A strict screening regime must continue to be used as the infections are still present albeit in small numbers.

[Research activities in Kobe-Indonesia Collaborative Research Centers].

PubMed

Utsumi, Takako; Hayashi, Yoshitake; Hotta, Hak

2013-01-01

Kobe-Indonesia Collaborative Research Center was established in Institute of Tropical Disease (ITD), Airlangga University, Surabaya, Indonesia in 2007 under the program of ''Founding Research Centers for Emerging and Reemerging Infectious Diseases'' supported by the Ministry of Education, Culture, Sports, Science and Technology, Japan, and then it has been under the Japan Initiative for Global Research Network on Infectious Diseases (J-GRID) since 2010. Japanese researchers have been stationed at ITD, conducting joint researches on influenza, viral hepatitis, dengue and infectious diarrhea. Also, another Japanese researcher has been stationed at Faculty of Medicine, University of Indonesia, Jakarta, carrying out joint researches on'' Identification of anti-hepatitis C virus (HCV) substances and development of HCV and dengue vaccines'' in collaboration with University of Indonesia and Airlangga University through the Science and Technology Research Partnership for Sustainable Development (SATREPS) supported by the Japan Science and Technology Agency (JST) and Japan International Cooperation Agency (JICA) since 2009. In this article, we briefly introduce the background history of Kobe University Research Center in Indonesia, and discuss the research themes and outcomes of J-GRID and SATREPS activities.

Anti-HCV effect of Lentinula edodes mycelia solid culture extracts and low-molecular-weight lignin.

PubMed

Matsuhisa, Koji; Yamane, Seiji; Okamoto, Toru; Watari, Akihiro; Kondoh, Masuo; Matsuura, Yoshiharu; Yagi, Kiyohito

2015-06-19

Lentinula edodes mycelia solid culture extract (MSCE) contains several bioactive molecules, including some polyphenolic compounds, which exert immunomodulatory, antitumor, and hepatoprotective effects. In this study, we examined the anti-hepatitis C virus (HCV) activity of MSCE and low-molecular-weight lignin (LM-lignin), which is the active component responsible for the hepatoprotective effect of MSCE. Both MSCE and LM-lignin inhibited the entry of two HCV pseudovirus (HCVpv) types into Huh7.5.1 cells. LM-lignin inhibited HCVpv entry at a lower concentration than MSCE and inhibited the entry of HCV particles in cell culture (HCVcc). MSCE also inhibited HCV subgenome replication. LM-lignin had no effect on HCV replication, suggesting that MSCE contains additional active substances. We demonstrate here for the first time the anti-HCV effects of plant-derived LM-lignin and MSCE. The hepatoprotective effect of LM-lignin suggests that lignin derivatives, which can be produced in abundance from existing plant resources, may be effective in the treatment of HCV-related diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

[Vaccination against viral hepatitis A and B in adults aged over 40 years--antibody persistence and immune memory].

PubMed

Chlibek, R; Smetana, J; Bostíková, V; Splino, M

2011-09-01

Primary vaccination with combined vaccine against viral hepatitis A (VHA) and viral hepatitis B (VHB) induces higher anti-hepatitis B surface (anti-HBs) antibody responses and similar anti-hepatitis A virus (anti-HAV) antibody responses in adults aged over 40 years in comparison with concomitant monovalent vaccines against VHA and VHB. Th e objectives were to assess, in a clinical study, persistence of anti-HAV and anti-HBs antibodies in adults aged over 40 years four years after primary VHA/VHB vaccination and antibody response following a booster dose of the vaccine. Five hundred and ninety-six subjects aged > 40 years were vaccinated with three doses of the combined VHA/VHB vaccine at Months 0, 1, 6 (HAB group) or with concomitant VHA and VHB vaccines at Months 0, 6 and 0, 1, 6 (ENG+HAV and HBVX+VAQ, respectively). Blood samples were collected one month following primary vaccination (Month 7) and then at one-year intervals for four years after the booster dose with the same vaccine as used for the primary vaccination. The anti-HBs and anti-HAV antibody levels were determined prior to the booster dose and at days 14 and 30 after the booster dose. At Month 7, > 97% of study subjects were seropositive for anti-HAV antibodies in all groups analyzed. Four years after primary vaccination, anti-HAV antibody seropositivity persisted in > 93% of study subjects, increasing to > 99% after the booster dose. At Month 7, the highest proportion of study subjects with anti-HBs antibody levels > or = 10 mIU/ml was found in the HAB group (91.7% versus 79.7% in the ENG+HAV group versus 71.0% in the HBVX+VAQ group). Four years after vaccination, anti-HBs antibody levels of 10 mIU/ml persisted in 57.1% of the HAB study subjects in comparison with 40.1% and 26.6% of the study subjects in the ENG+HAV and HBVX+VAQ groups, respectively. One month after the booster dose, anti-HBs antibody levels increased and antibody levels > or = 10 mIU/ml was achived in 95.2% of study subjects in the

The anti-hepatitis drug use effect and inventory management optimization from the perspective of hospital drug supply chain.

PubMed

Liu, Zhanyu

2017-09-01

By analyzing the current hospital anti hepatitis drug use, dosage, indications and drug resistance, this article studied the drug inventory management and cost optimization. The author used drug utilization evaluation method, analyzed the amount and kind distribution of anti hepatitis drugs and made dynamic monitoring of inventory. At the same time, the author puts forward an effective scheme of drug classification management, uses the ABC classification method to classify the drugs according to the average daily dose of drugs, and implements the automatic replenishment plan. The design of pharmaceutical services supply chain includes drug procurement platform, warehouse management system and connect to the hospital system through data exchange. Through the statistical analysis of drug inventory, we put forward the countermeasures of drug logistics optimization. The results showed that drug replenishment plan can effectively improve drugs inventory efficiency.

Role of occult hepatitis B virus infection in chronic hepatitis C

PubMed Central

Coppola, Nicola; Onorato, Lorenzo; Pisaturo, Mariantonietta; Macera, Margherita; Sagnelli, Caterina; Martini, Salvatore; Sagnelli, Evangelista

2015-01-01

The development of sensitive assays to detect small amounts of hepatitis B virus (HBV) DNA has favored the identification of occult hepatitis B infection (OBI), a virological condition characterized by a low level of HBV replication with detectable levels of HBV DNA in liver tissue but an absence of detectable surface antigen of HBV (HBsAg) in serum. The gold standard to diagnose OBI is the detection of HBV DNA in the hepatocytes by highly sensitive and specific techniques, a diagnostic procedure requiring liver tissue to be tested and the use of non-standardized non-commercially available techniques. Consequently, in everyday clinical practice, the detection of anti-hepatitis B core antibody (anti-HBc) in serum of HBsAg-negative subjects is used as a surrogate marker to identify patients with OBI. In patients with chronic hepatitis C (CHC), OBI has been identified in nearly one-third of these cases. Considerable data suggest that OBI favors the increase of liver damage and the development of hepatocellular carcinoma (HCC) in patients with CHC. The data from other studies, however, indicate no influence of OBI on the natural history of CHC, particularly regarding the risk of developing HCC. PMID:26576082

Prevalence of human immunodeficiency virus, syphilis, hepatitis B and C in blood donations in Namibia

PubMed Central

2014-01-01

Background Transfusion Transmissible Infections (TTIs) such as Human Immunodeficiency Virus (HIV), syphilis, hepatitis B virus (HBV) and hepatitis C virus (HCV) are infections which are common in some communities in Southern Africa. It is important to screen blood donations for these infections. Methods This is a retrospective study which involved reviewing of previous blood donation records for the year 2012 in Namibia. The records were analyzed to determine the prevalence of HIV, syphilis, Hepatitis B and C among blood donations with regard to gender, age and geographical region of the donors. Results The findings indicated a significantly low prevalence of HIV, syphilis, HBsAg and anti-Hepatitis C among the blood donations. A low infection rate of 1.3% by any of the four tested TTIs was found among the blood donations given by the donor population in Namibia in 2012. Conclusion The blood donations given by the donor population in Namibia has a low infection rate with the HIV, syphilis, HBsAg and anti-HCV. A strict screening regime must continue to be used as the infections are still present albeit in small numbers. PMID:24884633

Saponin Inhibits Hepatitis C Virus Propagation by Up-regulating Suppressor of Cytokine Signaling 2

PubMed Central

Kang, Sang-Min; Min, Saehong; Son, Kidong; Lee, Han Sol; Park, Eun Mee; Ngo, Huong T. T.; Tran, Huong T. L.; Lim, Yun-Sook; Hwang, Soon B.

2012-01-01

Saponins are a group of naturally occurring plant glycosides which possess a wide range of pharmacological properties, including anti-tumorigenic and antiviral activities. To investigate whether saponin has anti-hepatitis C virus (HCV) activity, we examined the effect of saponin on HCV replication. HCV replication was efficiently inhibited at a concentration of 10 µg/ml of saponin in cell culture grown HCV (HCVcc)-infected cells. Inhibitory effect of saponin on HCV replication was verified by quantitative real-time PCR, reporter assay, and immunoblot analysis. In addition, saponin potentiated IFN-α-induced anti-HCV activity. Moreover, saponin exerted antiviral activity even in IFN-α resistant mutant HCVcc-infected cells. To investigate how cellular genes were regulated by saponin, we performed microarray analysis using HCVcc-infected cells. We demonstrated that suppressor of cytokine signaling 2 (SOCS2) protein level was distinctively increased by saponin, which in turn resulted in inhibition of HCV replication. We further showed that silencing of SOCS2 resurrected HCV replication and overexpression of SOCS2 suppressed HCV replication. These data imply that saponin inhibits HCV replication via SOCS2 signaling pathway. These findings suggest that saponin may be a potent therapeutic agent for HCV patients. PMID:22745742

Simplification of antiretroviral therapy: a necessary step in the public health response to HIV/AIDS in resource-limited settings.

PubMed

Vitoria, Marco; Ford, Nathan; Doherty, Meg; Flexner, Charles

2014-01-01

The global scale-up of antiretroviral therapy (ART) over the past decade represents one of the great public health and human rights achievements of recent times. Moving from an individualized treatment approach to a simplified and standardized public health approach has been critical to ART scale-up, simplifying both prescribing practices and supply chain management. In terms of the latter, the risk of stock-outs can be reduced and simplified prescribing practices support task shifting of care to nursing and other non-physician clinicians; this strategy is critical to increase access to ART care in settings where physicians are limited in number. In order to support such simplification, successive World Health Organization guidelines for ART in resource-limited settings have aimed to reduce the number of recommended options for first-line ART in such settings. Future drug and regimen choices for resource-limited settings will likely be guided by the same principles that have led to the recommendation of a single preferred regimen and will favour drugs that have the following characteristics: minimal risk of failure, efficacy and tolerability, robustness and forgiveness, no overlapping resistance in treatment sequencing, convenience, affordability, and compatibility with anti-TB and anti-hepatitis treatments.

Acute hepatitis C in an HIV-infected patient: a case report and review of literature.

PubMed

Driver, Todd H; Terrault, Norah; Saxena, Varun

2013-05-01

With the decrease in transmission via transfusions and injection drug use, acute symptomatic hepatitis C is infrequently seen in developed countries. We report a case of a human immunodeficiency virus (HIV)-infected adult who presented with abdominal pain. His alanine aminotransferase was greater than sixty times the upper limit of normal without any evidence on examination of fulminant hepatic failure. His workup revealed an elevated hepatitis C viral level with a negative hepatitis C antibody. He was discharged once his liver function tests improved. As an outpatient, he had a recurrent bout of symptoms with an elevation of his alanine aminotransferase and hepatitis C viral levels that promoted anti-hepatitis C virus treatment. This case illustrates the importance of considering acute hepatitis C as a cause of acute hepatitis in HIV-infected men who have sex with men. While patients with acute symptomatic hepatitis C generally have a higher rate of spontaneous viral clearance compared to those with an insidious acute infection, most still progress to chronic hepatitis C infection, and patients with HIV coinfection carry a higher risk of progression to chronic disease.

Oxymatrine lightened the inflammatory response of LPS-induced mastitis in mice through affecting NF-κB and MAPKs signaling pathways.

PubMed

Yang, Zhengtao; Yin, Ronglan; Cong, Yunfeng; Yang, Zhanqing; Zhou, Ershun; Wei, Zhengkai; Liu, Zhicheng; Cao, Yongguo; Zhang, Naisheng

2014-12-01

Mastitis, an inflammatory reaction of the mammary gland, is recognized as one of the most costly diseases in dairy cattle. Oxymatrine, one of the alkaloids extracted from Chinese herb Sophora flavescens Ait, has been reported to have many biological activities, such as anti-inflammatory, anti-virus, and anti-hepatic fibrosis properties. The aim of this study was to investigate the protective effect and the anti-inflammatory mechanism of oxymatrine on lipopolysaccharide (LPS)-induced mastitis in mice. The mouse mastitis was induced by 10 μg of LPS for 24 h. Oxymatrine was intraperitoneally administered with the dose of 30, 60, and 120 mg/kg 1 h before and 12 h after LPS induction. The results showed that oxymatrine significantly attenuated the damage of the mammary gland induced by LPS. Oxymatrine inhibited the phosphorylation of NF-κB p65 and IκB in NF-κB signal pathway and reduced the phosphorylation of p38, ERK, and JNK in mitogen-activated protein kinase (MAPKs) signal pathway. The results showed that oxymatrine had a protective effect on LPS-induced mastitis, and the anti-inflammatory mechanism of oxymatrine was related to the inhibition of NF-κB and MAPKs signal pathways.

Hospital-based allogenic bone bank--10-year experience.

PubMed

Hou, C-H; Yang, R-S; Hou, S-M

2005-01-01

Bone banking in a hospital provides resources of allogenic bone grafts. However, they may transmit infection from donor to recipient. We found few reports discussing the infection rate and monitoring processes associated with bone banks. The discard rate using the screening test was 18.5% (309/1674) in this series. The leading cause was hepatitis B antigen (HBsAg) positive donor serum (67%), followed by Venereal Disease Research Laboratory (VDRL) positive donor serum (15%), and anti-hepatitis C virus (HCV) positive donor serum (12%). The overall infection rate in the recipients was 1.3% (17/1365). Among 1353 implanted allografts, 22 cases (1.6%) had a positive swab culture result after thawing. Only four out of these 22 cases (18.2%) developed infection. However, the wound cultures of the infected recipients were different from the swab culture of thawing allografts except in one case. Among the 1331 recipients with sterile allograft bones, 13 (1%) were found to have infection. In conclusion, our bone bank operates under a strict monitoring system which results in a low infection rate. The recipient's status, the aseptic technique and environment during operation is likely to be more critical in prevention of allograft-related infection.

Modern perspectives on the health benefits of kefir in next generation sequencing era: Improvement of the host gut microbiota.

PubMed

Kim, Dong-Hyeon; Jeong, Dana; Kim, Hyunsook; Seo, Kun-Ho

2018-01-16

Kefir is a natural complex fermented milk product containing more than 50 species of probiotic bacteria and yeast, and has been demonstrated to have multiple properties conferring health benefits, including antiobesity, anti-hepatic steatosis, antioxidative, antiallergenic, antitumor, anti-inflammatory, cholesterol-lowering, constipation-alleviating, and antimicrobial properties. To better understand the underlying mechanisms of these benefits, we here review research on the effect of kefir (and kefir microorganisms) consumption to modulate the host gut microbiota. Owing to its excellent gastrointestinal resistance and colonization ability and wide ranges of microbial interaction, kefir has shown significant and wide-spectrum modulatory effects on the host gut microbiota. In particular, as a bacteria- and yeast-containing food, kefir can modulate both the gut microbiota and mycobiota. Since the association of this modulation with health benefit has only been addressed in a small number of recent studies thus far, further studies are needed to determine the precise mechanisms of the beneficial effects of kefir in relation to the modulation of the gut microbiota and mycobiota. Gaining this insight will surely help to take full advantage of this unique probiotic food.

Hepatitis B virus surface antigen and anti-hepatitis C virus rapid tests underestimate hepatitis prevalence among HIV-infected patients.

PubMed

Hønge, Bl; Jespersen, S; Medina, C; Té, Ds; da Silva, Zj; Ostergaard, L; Laursen, Al; Wejse, C; Krarup, H; Erikstrup, C

2014-10-01

In the case of coinfection with HIV and hepatitis B virus (HBV) and/or hepatitis C virus (HCV), hepatic disease progression is often accelerated, with higher rates of liver cirrhosis and liver-related mortality. We aimed to evaluate the performance of the rapid tests used routinely to detect HBV surface antigen (HBsAg) and anti-HCV among HIV-infected patients in Guinea-Bissau. Blood samples from HIV-infected patients in Guinea-Bissau were stored after testing for HBsAg and anti-HCV with rapid tests. Samples were subsequently re-tested for HBsAg and anti-HCV in Denmark. Two rapid tests were used in Guinea-Bissau: HBsAg Strip Ref 2034 (VEDA.LAB, Alençon, France; sensitivity 62.3%; specificity 99.2%) and HEPA-SCAN (Bhat Bio-Tech, Bangalore, India; sensitivity 57.1%; specificity 99.7%). In the two tests the ability to obtain the correct outcome depended on the antigen and antibody concentrations, respectively. Sex, age, CD4 cell count and antiretroviral therapy status did not differ between false negative and true positive samples in either of the tests. The study is limited by a low number of anti-HCV positive samples. New diagnostic rapid tests should always be evaluated in the setting in which they will be used before implementation. © 2014 British HIV Association.

Anti-hepatitis C virus activity and synergistic effect of Nymphaea alba extracts and bioactive constituents in liver infected cells.

PubMed

Rehman, Sidra; Ashfaq, Usman Ali; Ijaz, Bushra; Riazuddin, Sheikh

2018-05-28

Without an effective vaccine, hepatitis C virus (HCV) remains a global threat, inflicting 170-300 million carriers worldwide at risk of cirrhosis and hepatocellular carcinoma (HCC). Though various direct acting antivirals have been redeemed the hepatitis C treatment, a few restraints persist including possible side effects, viral resistance emergence, excessive cost which restricts its availability to a common person. There is no preventive HCV vaccine available today so the discovery of potent antiviral natural flora and their bioactive constituents may help to develop preventive cures against HCV infection. In current study, we aim to clarify anti-HCV activity of methanol and acetone extracts along with the purified fractions of Pakistani local plant, Nymphaea alba L (N. alba) using Huh-7 cell line as transfection model. Synergistic study of purified fractions with interferon was performed using MDBK cell line (expressing interferon receptors) as transfection model. Recent study by our research group has observed potent anti-HCV NS3 protease activity of methanol and acetone extracts of N. alba. Effect of N. alba extracts, its fractions precisely, the N1 and N8 fractions on HCV replication was demonstrated by analyzing viral gene expression using in vitro transfection model. Considering NS3 protease as a dynamic drug target, fourteen phytochemicals of N. alba were selected as ligands for interaction with NS3 protein using Molecular Operating Environment (MOE) software. Boceprevir, FDA approved NS3 protease inhibitor, was used as standard for comparative study in docking screening. Herein we report 84% and 94% reduction of 3a genotype of HCV NS3/4A gene expression at mRNA level at non-toxic concentration. Specifically, two fractions 'N1' & 'N8' isolated from acetone extract suppressed HCV NS3 gene expression in transfected target cells with an EC 50 value of 37 ± 0.03 μg/ml and 20 ± 0.02 μg/ml respectively. Similarly, viral genotype 1a replication is strongly suppressed in target cells by N. alba flower extracts and purified fractions. Moreover, combination of fractions with standard antiviral drug displayed synergistic effects for inhibition of HCV replication. Phytochemicals including Isoquercetin, Hyperoside, Quercetin, Reynoutrin, Apigenin and Isokaempferide displayed minimum binding energies as compared to standard protease inhibitor. N. alba and its purified phytochemicals with new scaffolds might significantly serve as valuable and alternative regimen against HCV either alone or in combination with other potential anti-HCV agents. Copyright © 2018 Elsevier Ltd. All rights reserved.

Bioactivity-guided isolation of anti-hepatitis B virus active sesquiterpenoids from the traditional Chinese medicine: Rhizomes of Cyperus rotundus.

PubMed

Xu, Hong-Bo; Ma, Yun-Bao; Huang, Xiao-Yan; Geng, Chang-An; Wang, Hao; Zhao, Yong; Yang, Tong-Hua; Chen, Xing-Long; Yang, Cai-Yan; Zhang, Xue-Mei; Chen, Ji-Jun

2015-08-02

The rhizome of Cyperus rotundus (C. rotundus) is a well-known traditional Chinese medicine to cure hepatitis in many formulae, but the active components responsible for hepatitis have not been elucidated. According to our bioassay on HepG2.2.15 cell line in vitro, the ethanol extract of C. rotundus demonstrated potent anti-HBV activity. This current study was designed to isolate and identify the anti-HBV active constituents from the rhizomes of C. rotundus. Bioactivity and LC-MS guided fractionation on the extract of C. rotundus using various chromatographic techniques including open-column, Sephadex LH-20 and semi-preparative high performance liquid chromatography led to the isolation and identification of thirty-seven sesquiterpenoids. Structural elucidation of the isolates was carried out by extensive spectroscopic analyses (UV, IR, HRMS, 1D- and 2D -NMR). The anti-HBV activity and cytotoxicity were evaluated on the HBV-transfected HepG2.2.15 cell line in vitro. The cytotoxicity effects of the isolates were assessed by a MTT assay. The secretions of HBsAg and HBeAg in the culture medium were detected by ELISA method, and the load of HBV DNA was quantified by real-time fluorescent PCR technique. Five new patchoulane-type sesquiterpenoids, namely cyperene-3, 8-dione (1), 14-hydroxy cyperotundone (2), 14-acetoxy cyperotundone (3), 3β-hydroxycyperenoic acid (4) and sugetriol-3, 9-diacetate (5), along with 32 known sesquiterpenoids were isolated from the active fractions of C. rotundus. Compounds 2 and 3 were the first cyperotundone-type sesquiterpenoids with a hydroxyl group at C-14 position. Nine eudesmane-type sesquiterpenoids (15-21 and 23-24) significantly inhibited the HBV DNA replication with IC50 values of 42.7±5.9, 22.5±1.9, 13.2±1.2, 10.1±0.7, 14.1±1.1, 15.3±2.7, 13.8±0.9, 19.7±2.1 and 11.9±0.6 μM, respectively, of which, compounds 17, 21, 23 and 24 possessed high SI values of 250.4, 125.5,>259.6 and 127.5, respectively. Two patchoulane-type sesquiterpenoids (4 and 7) effectively suppressed the secretion of HBsAg in a dose-dependent manner with IC50 values of 46.6±14.3 (SI=31.0) and 77.2±13.0 (SI=1.7) μM, respectively. Compounds 2, 8, 12, 15, 17 and 25 possessed moderate activities against HBeAg secretion with IC50 values of 162.5±18.9 (SI=13.3), 399.2±90.0 (SI=10.6), 274.7±70.8 (SI=5.2), 313.9±87.5 (SI=7.2), 334.0±70.4 (SI=9.9) and 285.3±20.9 (SI=15.5) μM, respectively. This is the first study to reveal the anti-HBV constituents of C. rotundus, demonstrating that the eudesmane-type sesquiterpenoids might contribute to the anti-HBV activity of the rhizomes of C. rotundus. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Prevalence of hepatitis D virus infection in sub-Saharan Africa: a systematic review and meta-analysis.

PubMed

Stockdale, Alexander J; Chaponda, Mas; Beloukas, Apostolos; Phillips, Richard Odame; Matthews, Philippa C; Papadimitropoulos, Athanasios; King, Simon; Bonnett, Laura; Geretti, Anna Maria

2017-10-01

Hepatitis D virus (also known as hepatitis delta virus) can establish a persistent infection in people with chronic hepatitis B, leading to accelerated progression of liver disease. In sub-Saharan Africa, where HBsAg prevalence is higher than 8%, hepatitis D virus might represent an important additive cause of chronic liver disease. We aimed to establish the prevalence of hepatitis D virus among HBsAg-positive populations in sub-Saharan Africa. We systematically reviewed studies of hepatitis D virus prevalence among HBsAg-positive populations in sub-Saharan Africa. We searched PubMed, Embase, and Scopus for papers published between Jan 1, 1995, and Aug 30, 2016, in which patient selection criteria and geographical setting were described. Search strings included sub-Saharan Africa, the countries therein, and permutations of hepatitis D virus. Cohort data were also added from HIV-positive populations in Malawi and Ghana. Populations undergoing assessment in liver disease clinics and those sampled from other populations (defined as general populations) were analysed. We did a meta-analysis with a DerSimonian-Laird random-effects model to calculate a pooled estimate of hepatitis D virus seroprevalence. Of 374 studies identified by our search, 30 were included in our study, only eight of which included detection of hepatitis D virus RNA among anti-hepatitis D virus seropositive participants. In west Africa, the pooled seroprevalence of hepatitis D virus was 7·33% (95% CI 3·55-12·20) in general populations and 9·57% (2·31-20·43) in liver-disease populations. In central Africa, seroprevalence was 25·64% (12·09-42·00) in general populations and 37·77% (12·13-67·54) in liver-disease populations. In east and southern Africa, seroprevalence was 0·05% (0·00-1·78) in general populations. The odds ratio for anti-hepatitis D virus detection among HBsAg-positive patients with liver fibrosis or hepatocellular carcinoma was 5·24 (95% CI 2·74-10·01; p<0·0001

Targeting Phosphatidylinositol 4-Kinase IIIα for Radiosensitization: A Potential Model of Drug Repositioning Using an Anti-Hepatitis C Viral Agent

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwon, Jeanny; Kim, Dan Hyo; Park, Ji Min

Purpose: To investigate which isotype of phosphatidylinositol 4-kinase (PI4K) may affect radiosensitivity and examine whether anti–hepatitis C viral (HCV) agents, some of which have been shown to inhibit PI4K IIIα activity, could be repositioned as a radiosensitizer in human cancer cells. Methods and Materials: U251, BT474, and HepG2 cell lines and normal human astrocyte were used. Ribonucleic acid interference, clonogenic assays, Western blotting, immunofluorescence, annexin V assay, lysotracker staining, and β-galactosidase assay were performed. Results: Of the 4 PI4K isotypes, specific inhibition of IIIα increased radiosensitivity. For pharmacologic inhibition of PI4K IIIα, we screened 9 anti-HCV agents by half-maximal inhibitorymore » concentration assay. Simeprevir was selected, and its inhibition of PI4K IIIα activity was confirmed. Combination of simeprevir treatment and radiation significantly attenuated expression of phospho-phospho-PKC and phospho-Akt and increased radiation-induced cell death in tested cell lines. Pretreatment with simeprevir prolonged γH2AX foci formation and down-regulation of phospho-DNA-PKcs, indicating impairment of nonhomologous end-joining repair. Cells pretreated with simeprevir exhibited mixed modes of cell death, including apoptosis and autophagy. Conclusion: These data demonstrate that targeting PI4K IIIα using an anti-HCV agent is a viable approach to enhance the therapeutic efficacy of radiation therapy in various human cancers, such as glioma, breast, and hepatocellular carcinoma.« less

The infective causes of hepatitis and jaundice amongst hospitalised patients in Vientiane, Laos

PubMed Central

Syhavong, Bounkong; Rasachack, Bouachanh; Smythe, Lee; Rolain, Jean-Marc; Roque-Afonso, Anne-Marie; Jenjaroen, Kemajittra; Soukkhaserm, Vimone; Phongmany, Simmaly; Phetsouvanh, Rattanaphone; Soukkhaserm, Sune; Thammavong, Te; Mayxay, Mayfong; Blacksell, Stuart D.; Barnes, Eleanor; Parola, Philippe; Dussaix, Elisabeth; Raoult, Didier; Humphreys, Isla; Klenerman, Paul; White, Nicholas J.; Newton, Paul N.

2010-01-01

Summary There is little information on the diverse infectious causes of jaundice and hepatitis in the Asiatic tropics. Serology (hepatitis A, B, C and E, leptospirosis, dengue, rickettsia), antigen tests (dengue), PCR assays (hepatitis A, C and E) and blood cultures (septicaemia) were performed on samples from 392 patients admitted with jaundice or raised transaminases (≥ × 3) to Mahosot Hospital, Vientiane, Laos over 3 years. Conservative definitions suggested diagnoses of dengue (8.4%), rickettsioses (7.3%), leptospirosis (6.8%), hepatitis B (4.9%), hepatitis C (4.9%), community-acquired septicaemia (3.3%) and hepatitis E (1.6%). Although anti-hepatitis A virus (HAV) IgM antibody results suggested that 35.8% of patients had acute HAV infections, anti-HAV IgG antibody avidity and HAV PCR suggested that 82% had polyclonal activation and not acute HAV infections. Scrub typhus, murine typhus or leptospirosis were present in 12.8% of patients and were associated with meningism and relatively low AST and ALT elevation. These patients would be expected to respond to empirical doxycycline therapy which, in the absence of virological diagnosis and treatment, may be an appropriate cost-effective intervention in Lao patients with jaundice/hepatitis. PMID:20378138

A network pharmacology approach to discover active compounds and action mechanisms of San-Cao Granule for treatment of liver fibrosis.

PubMed

Wei, Shizhang; Niu, Ming; Wang, Jian; Wang, Jiabo; Su, Haibin; Luo, Shengqiang; Zhang, Xiaomei; Guo, Yanlei; Liu, Liping; Liu, Fengqun; Zhao, Qingguo; Chen, Hongge; Xiao, Xiaohe; Zhao, Pan; Zhao, Yanling

2016-01-01

San-Cao Granule (SCG) has been used in patients with liver fibrosis for many years and has shown good effect. However, its mechanism of therapeutic action is not clear because of its complex chemical system. The purpose of our study is to establish a comprehensive and systemic method that can predict the mechanism of action of SCG in antihepatic fibrosis. In this study, a "compound-target-disease" network was constructed by combining the SCG-specific and liver fibrosis-specific target proteins with protein-protein interactions, and network pharmacology was used to screen out the underlying targets and mechanisms of SCG for treatment of liver fibrosis. Then, some key molecules of the enriched pathway were chosen to verify the effects of SCG on liver fibrosis induced by thioacetamide (TAA). This systematic approach had successfully revealed that 16 targets related to 11 SCG compounds were closely associated with liver fibrosis therapy. The pathway-enrichment analysis of them showed that the TGF-β1/Smad signaling pathway is relatively important. Animal experiments also proved that SCG could significantly ameliorate liver fibrosis by inhibiting the TGF-β1/Smad pathway. SCG could alleviate liver fibrosis through the molecular mechanisms predicted by network pharmacology. Furthermore, network pharmacology could provide deep insight into the pharmacological mechanisms of Chinese herbal formulas.

Sedum mexicanum Britt. Induces Apoptosis of Primary Rat Activated Hepatic Stellate Cells.

PubMed

Lee, Shou-Lun; Chin, Ting-Yu; Lai, Ching-Long; Wang, Wen-Han

2015-01-01

Background. Liver fibrosis is a significant liver disease in Asian countries. Sedum mexicanum Britt. (SM) has been claimed to have antihepatitis efficacy. In traditional folk medicine, a solution of boiling water-extracted SM (SME) is consumed to prevent and treat hepatitis. However, its efficacy has not yet been verified. The purpose of this study was to investigate the in vitro effect of SME on hepatoprotection. Methods. Hepatic stellate cells (HSCs) and hepatocytes (HCs) were isolated from the livers of the rats by enzymatic digestion and density gradient centrifugation. Results. Treating the HCs and aHSCs with SME caused a dose-dependent decrease in the viability of aHSCs but not that of HCs. In addition, treatment with SME resulted in apoptosis of aHSCs, as determined by DAPI analysis and flow cytometry. SME also increased the amount of cleaved caspase-3, cleaved caspase-9, and cleaved poly ADP-ribose polymerase (PARP) in aHSCs. Furthermore, SME treatment induced a dose-dependent reduction in Bcl-2 expression and increased the expression of Bax in aHSCs. Conclusions. SME did not cause cytotoxicity in HCs, but it induced apoptosis in aHSCs through the mitochondria-dependent caspase-3 pathway. Therefore, SME may possess therapeutic potential for liver fibrosis.

Sedum mexicanum Britt. Induces Apoptosis of Primary Rat Activated Hepatic Stellate Cells

PubMed Central

Lee, Shou-Lun; Chin, Ting-Yu; Lai, Ching-Long; Wang, Wen-Han

2015-01-01

Background. Liver fibrosis is a significant liver disease in Asian countries. Sedum mexicanum Britt. (SM) has been claimed to have antihepatitis efficacy. In traditional folk medicine, a solution of boiling water-extracted SM (SME) is consumed to prevent and treat hepatitis. However, its efficacy has not yet been verified. The purpose of this study was to investigate the in vitro effect of SME on hepatoprotection. Methods. Hepatic stellate cells (HSCs) and hepatocytes (HCs) were isolated from the livers of the rats by enzymatic digestion and density gradient centrifugation. Results. Treating the HCs and aHSCs with SME caused a dose-dependent decrease in the viability of aHSCs but not that of HCs. In addition, treatment with SME resulted in apoptosis of aHSCs, as determined by DAPI analysis and flow cytometry. SME also increased the amount of cleaved caspase-3, cleaved caspase-9, and cleaved poly ADP-ribose polymerase (PARP) in aHSCs. Furthermore, SME treatment induced a dose-dependent reduction in Bcl-2 expression and increased the expression of Bax in aHSCs. Conclusions. SME did not cause cytotoxicity in HCs, but it induced apoptosis in aHSCs through the mitochondria-dependent caspase-3 pathway. Therefore, SME may possess therapeutic potential for liver fibrosis. PMID:26078767

The British HIV Association national audit on the management of subjects co-infected with HIV and hepatitis B/C.

PubMed

Garvey, L; Curtis, H; Brook, G

2011-03-01

The aim of this work was to survey current service provision and adherence to the British HIV Association (BHIVA) guidelines for the management of HIV and hepatitis B/C co-infected patients in the UK. Sites were invited to complete a survey of local care arrangements for co-infected patients. A case-note audit of all co-infected attendees during a six-month period in 2009 was performed. Data including demographics, clinical parameters, hepatitis disease status, antiretroviral and hepatitis B/C therapy were collected. Using BHIVA guidelines as audit standards, the proportion of sites and subjects meeting each standard was calculated. One-hundred and forty sites (75%) responded and data from 973 eligible co-infected patients were submitted. Approximately a third of sites reported not re-checking hepatitis serology or vaccination titres annually. Of all co-infected patients, 122 (13%) were neither vaccinated nor immune to hepatitis A and 26 (5%) of patients with hepatitis C were neither vaccinated nor naturally immune to hepatitis B. Of HBsAg-positive subjects, 25 (6%) were receiving lamivudine as the sole drug with antihepatitis B activity. In the UK, the management of HIV and hepatitis B/C co-infection remains highly variable. Optimizing the care of this high-risk patient group is a priority.

Identification of BMS-200475 as a potent and selective inhibitor of hepatitis B virus.

PubMed Central

Innaimo, S F; Seifer, M; Bisacchi, G S; Standring, D N; Zahler, R; Colonno, R J

1997-01-01

BMS-200475 is a novel carbocyclic 2'-deoxyguanosine analog found to possess potent and selective anti-hepatitis B virus (anti-HBV) activity. BMS-200475 is distinguished from guanosine by replacement of the natural furanose oxygen on the sugar moiety with an exo carbon-carbon double bond. In the HepG2 stably transfected cell line 2.2.15, BMS-200475 had a 50% effective concentration (EC50) of 3.75 nM against HBV, as determined by analysis of secreted HBV DNA. Structurally related compounds with adenine, iodouracil, or thymine base substitutions were significantly less potent or were inactive. Direct comparison of the antiviral activities of BMS-200475 with those of a variety of other nucleoside analogs, including lamivudine (EC50 = 116.26 nM), demonstrated the clearly superior in vitro potency of BMS-200475 in 2.2.15 cells. Intracellular HBV replicative intermediates were uniformly reduced when cells were treated with BMS-200475, but rebounded after treatment was terminated. The concentration of BMS-200475 causing 50% cytotoxicity in 2.2.15 cell cultures was 30 microM, approximately 8,000-fold greater than the concentration required to inhibit HBV replication in the same cell line. Treatment with BMS-200475 resulted in no apparent inhibitory effects on mitochondrial DNA content. PMID:9210663

Autoimmune hepatitis: a manifestation of immune reconstitution inflammatory syndrome in HIV infected patients?

PubMed

Murunga, Eric; Andersson, Monique; Rensburg, Christo van

2016-07-01

To describe a case series of patients presenting with autoimmune hepatitis after initiation of antiretroviral therapy. The demographics, clinical and laboratory features, and therapeutic response of HIV-infected patients on antiretroviral therapy presenting to our Division between November 2011 and November 2014 with elevated liver enzymes, were analysed. Nine patients with elevated liver enzymes, immunoglobulin G and autoimmune markers in keeping with autoimmune hepatitis were identified. All were anti-hepatitis C virus negative. One patient was hepatitis B surface antigen positive but his hepatitis B viral load was undetectable. All patients denied using any traditional herbal remedies. Liver histology was consistent with autoimmune hepatitis showing interface hepatitis and infiltrates of lymphocytes and plasma cells. Diagnosis was made according to the Autoimmune Hepatitis Group Scoring Systems. All patients were started on 15-20 mg of oral prednisone with clinical and biochemical improvement after 1-6 weeks. Immune reconstitution related autoimmune hepatitis should be considered in the differential diagnosis of hepatitis in the HIV-infected patient on antiretroviral therapy. Liver biopsy should be performed and the diagnosis confirmed using scoring systems developed by the Autoimmune Hepatitis Group. Timely treatment with prednisone and other agents for autoimmune hepatitis is indicated, and can be lifesaving in acute liver failure.

Oxymatrine induces human pancreatic cancer PANC-1 cells apoptosis via regulating expression of Bcl-2 and IAP families, and releasing of cytochrome c

PubMed Central

2011-01-01

Background Oxymatrine, an isolated extract from traditional Chinese herb Sophora Flavescens Ait, has been traditionally used for therapy of anti-hepatitis B virus, anti-inflammation and anti-anaphylaxis. The present study was to investigate the anti-cancer effect of oxymatrine on human pancreatic cancer PANC-1 cells, and its possible molecular mechanism. Methods The effect of oxymatrine on the viability and apoptosis was examined by methyl thiazolyl tetrazolium and flow cytometry analysis. The expression of Bax, Bcl-2, Bcl-x (L/S), Bid, Bad, HIAP-1, HIAP-2, XIAP, NAIP, Livin and Survivin genes was accessed by RT-PCR. The levels of cytochrome c and caspase 3 protein were assessed by Western blotting. Results Oxymatrine inhibited cell viability and induced apoptosis of PANC-1 cells in a time- and dose-dependent manner. This was accompanied by down-regulated expression of Livin and Survivin genes while the Bax/Bcl-2 ratio was upregulated. Furthermore, oxymatrine treatment led to the release of cytochrome c and activation of caspase-3 proteins. Conclusion Oxymatrine can induce apoptotic cell death of human pancreatic cancer, which might be attributed to the regulation of Bcl-2 and IAP families, release of mitochondrial cytochrome c and activation of caspase-3. PMID:21714853

Prevalence of hepatitis A viral RNA and antibodies among Chinese blood donors.

PubMed

Sun, P; Su, N; Lin, F Z; Ma, L; Wang, H J; Rong, X; Dai, Y D; Li, J; Jian, Z W; Tang, L H; Xiao, W; Li, C Q

2015-12-09

Like other developing countries, China was reported to have a relatively high seroprevalence of anti-hepatitis A antibodies (anti-HAV). However, no studies have evaluated the prevalence of anti-HAV and HAV RNA among voluntary blood donors with or without elevated serum alanine transaminase (ALT) levels. Anti-HAV antibodies were detected using an enzyme-linked immunosorbent assay, and reverse transcription quantitative polymerase chain reaction was carried out for detection of HAV RNA. In the current study, we analyzed a total of 450 serum samples with elevated ALT levels (≥40 U/L) and 278 serum samples with non-elevated ALT levels. Seroprevalence rates of anti-HAV were 51.6% in donors with elevated ALT and 41.4% in donors with non-elevated ALT; however, none of the samples was positive for HAV RNA. The results of our study showed lower seroprevalence rates of anti-HAV in blood donors (irrespective of ALT levels) than those in published data on Chinese populations. Although donors with elevated ALT had statistically higher prevalence rates of anti- HAV than did those with non-elevated ALT, none of the serum samples had detectable levels of the active virus. In conclusion, our results demonstrate that the transmission of hepatitis A by blood transfusion will occur rarely.

Synthesis and anti-HBV activity of α-stereoisomer of aristeromycin based analogs.

PubMed

Kasula, Mohan; Toyama, Masaaki; Samunuri, Ramakrishnamraju; Rozy, Farhana; Yadav, Monika; Bal, Chandralata; Jha, Ashok Kumar; Baba, Masanori; Sharon, Ashoke

2016-08-15

The potential antiviral activity of aristeromycin type of derivatives (I) is limited by associated toxicity due to its possible 5'-O-phosphorylation and S-adenosyl-l-homocysteine hydrolase (SAHase) inhibitory activity. Aristeromycin structure has major pharmacophoric motif as 5'-OH and adenosine base, which may have significant role in enzyme binding followed by activity and or toxicity. Thus, the structural optimization to alter this major motif by replacing with its bioisostere and changing the 5'-O conformation through stereochemistry reversal was of interest. Thus, the inverted stereochemistry at 4'-position coupled with bioisostere of adenosine base in the target compounds (6-7) to access antiviral potential. The stereoselective formation of a key stereoisomer (2a) was achieved exclusively from neplanocin sugar (1a) by reduction in a single step. The novel target molecules (6-7) were synthesized in 4 steps with 55-62% yield. Compound 6 was analyzed by single crystal X-ray diffraction, which confirms the stereoselective formation of α-analogs with highly puckered cyclopentane ring and 2'-endo conformation. The compound 6 shown significant anti-hepatitis B virus activity of 6.5μM with CC50>100μM and yielded a promising lead with novel structural feature. Copyright © 2016 Elsevier Ltd. All rights reserved.

An extra priming dose of hepatitis A vaccine to adult patients with rheumatoid arthritis and drug induced immunosuppression - A prospective, open-label, multi-center study.

PubMed

Rosdahl, Anja; Herzog, Christian; Frösner, Gert; Norén, Torbjörn; Rombo, Lars; Askling, Helena H

Previous studies have indicated that a pre-travel single dose of hepatitis A vaccine is not sufficient as protection against hepatitis A in immunocompromised travelers. We evaluated if an extra dose of hepatitis A vaccine given shortly prior to traveling ensures seroconversion. Patients with rheumatoid arthritis (n = 69, median age = 55 years) treated with Tumor Necrosis Factor inhibitor(TNFi) and/or Methotrexate (MTX) were immunized with two doses of hepatitis A vaccine, either as double dose or four weeks apart, followed by a booster dose at six months. Furthermore, 48 healthy individuals, median age = 60 years were immunized with two doses, six months apart. Anti-hepatitis A antibodies were measured at 0, 1, 2, 6, 7 and 12 months. Two months after the initial vaccination, 84% of the RA patients had protective antibodies, compared to 85% of the healthy individuals. There was no significant difference between the two vaccine schedules. At twelve months, 99% of RA patients and 100% of healthy individuals had seroprotective antibodies. An extra priming dos of hepatitis A vaccine prior to traveling offered an acceptable protection in individuals treated with TNFi and/or MTX. This constitutes an attractive pre-travel solution to this vulnerable group of patients. Copyright © 2017. Published by Elsevier Ltd.

Use of PCR in resolving diagnostic difficulties potentially caused by genetic variation of hepatitis B virus.

PubMed Central

van Deursen, F J; Hino, K; Wyatt, D; Molyneaux, P; Yates, P; Wallace, L A; Dow, B C; Carman, W F

1998-01-01

AIMS: To assess the relevance of genetic variants of hepatitis B virus (HBV) and to demonstrate the usefulness of the polymerase chain reaction (PCR) in cases of HBV diagnostic difficulty. METHODS: Five serum samples from patients that presented diagnostic difficulty in routine laboratories were sent to a research laboratory for PCR, and if appropriate, S gene sequencing, in vitro expression, and antigenic analysis. RESULTS: The demonstration of HBV in serum by PCR allowed a definitive diagnosis of current infection. One serum sample with poor reactivity in a diagnostic assay had a minor hepatitis B surface antigen (HBsAg) variant and another with very poor reactivity had multiple variants of HBsAg. Transient HBsAg reactivity was observed in a recently vaccinated patient. A hepatitis Be antigen (HBeAg) false positive reaction was noted in a patient from a well defined risk group for HBV. One patient who was strongly HBsAg/HBeAg positive, but anti-hepatitis B core antibody negative, was viraemic. CONCLUSIONS: PCR may become the gold standard for the diagnosis of current HBV infection. HBV variants are responsible for a proportion of diagnostically difficult cases. Modification of commercial assays is necessary to increase the sensitivity of detection of such variants. PMID:9602690

Inhibition of alpha interferon (IFN-α)-induced microRNA-122 negatively affects the anti-hepatitis B virus efficiency of IFN-α.

PubMed

Hao, Junli; Jin, Wensong; Li, Xinghui; Wang, Saifeng; Zhang, Xiaojun; Fan, Hongxia; Li, Changfei; Chen, Lizhao; Gao, Bin; Liu, Guangze; Meng, Songdong

2013-01-01

Alpha interferon (IFN-α)-based therapy can effectively treat chronic hepatitis B virus (HBV) infection, which causes life-threatening complications. Responses to IFN-α therapy vary greatly in chronic hepatitis B (CHB) patients, but underlying mechanisms are almost unknown. In this study, we found that IFN-α treatment induced a marked decrease of microRNA-122 (miR-122) expression in hepatocytes. We next showed that IFN-α-induced miR-122 downregulation was only partly due to transcriptional suppression. One IFN-stimulated gene (ISG), NT5C3, which was identified as a miR-122 target, efficiently inhibited miR-122 by binding and sequestering miR-122 with its mRNA 3'-untranslated region (3'-UTR), indicating that this ISG is involved in IFN-α-mediated miR-122 suppression. Notably, the inhibitory effect of IFN-α on miR-122 was completely abolished by blocking IFN-α-induced upregulation of NT5C3 mRNA expression by RNA interference (RNAi). Meanwhile, we observed that miR-122 dramatically inhibited HBV expression and replication. Finally, we showed that IFN-α-mediated HBV-inhibitory effects could be enhanced significantly by blocking IFN-α-induced downregulation of miR-122. We therefore concluded that IFN-α-induced inhibition of miR-122 may negatively affect the anti-HBV function of IFN-α. These data provide valuable insights for a better understanding of the antiviral mechanism of IFN-α and raise further potential interest in enhancing its anti-HBV efficacy.

Inhibition of Alpha Interferon (IFN-α)-Induced MicroRNA-122 Negatively Affects the Anti-Hepatitis B Virus Efficiency of IFN-α

PubMed Central

Hao, Junli; Jin, Wensong; Li, Xinghui; Wang, Saifeng; Zhang, Xiaojun; Fan, Hongxia; Li, Changfei; Chen, Lizhao; Gao, Bin

2013-01-01

Alpha interferon (IFN-α)-based therapy can effectively treat chronic hepatitis B virus (HBV) infection, which causes life-threatening complications. Responses to IFN-α therapy vary greatly in chronic hepatitis B (CHB) patients, but underlying mechanisms are almost unknown. In this study, we found that IFN-α treatment induced a marked decrease of microRNA-122 (miR-122) expression in hepatocytes. We next showed that IFN-α-induced miR-122 downregulation was only partly due to transcriptional suppression. One IFN-stimulated gene (ISG), NT5C3, which was identified as a miR-122 target, efficiently inhibited miR-122 by binding and sequestering miR-122 with its mRNA 3′-untranslated region (3′-UTR), indicating that this ISG is involved in IFN-α-mediated miR-122 suppression. Notably, the inhibitory effect of IFN-α on miR-122 was completely abolished by blocking IFN-α-induced upregulation of NT5C3 mRNA expression by RNA interference (RNAi). Meanwhile, we observed that miR-122 dramatically inhibited HBV expression and replication. Finally, we showed that IFN-α-mediated HBV-inhibitory effects could be enhanced significantly by blocking IFN-α-induced downregulation of miR-122. We therefore concluded that IFN-α-induced inhibition of miR-122 may negatively affect the anti-HBV function of IFN-α. These data provide valuable insights for a better understanding of the antiviral mechanism of IFN-α and raise further potential interest in enhancing its anti-HBV efficacy. PMID:23055569

Pre-Steady State Kinetic Investigation of the Incorporation of Anti-Hepatitis B Nucleotide Analogs Catalyzed by Non-Canonical Human DNA Polymerases

PubMed Central

Brown, Jessica A.; Pack, Lindsey R.; Fowler, Jason D.; Suo, Zucai

2011-01-01

Antiviral nucleoside analogs have been developed to inhibit the enzymatic activities of the hepatitis B virus (HBV) polymerase, thereby preventing the replication and production of HBV. However, the usage of these analogs can be limited by drug toxicity because the 5′-triphosphates of these nucleoside analogs (nucleotide analogs) are potential substrates for human DNA polymerases to incorporate into host DNA. Although they are poor substrates for human replicative DNA polymerases, it remains to be established whether these nucleotide analogs are substrates for the recently discovered human X- and Y-family DNA polymerases. Using pre-steady state kinetic techniques, we have measured the substrate specificity values for human DNA polymerases β, λ, η, ι, κ, and Rev1 incorporating the active forms of the following anti-HBV nucleoside analogs approved for clinical use: adefovir, tenofovir, lamivudine, telbivudine, and entecavir. Compared to the incorporation of a natural nucleotide, most of the nucleotide analogs were incorporated less efficiently (2 to >122,000) by the six human DNA polymerases. In addition, the potential for entecavir and telbivudine, two drugs which possess a 3′-hydroxyl, to become embedded into human DNA was examined by primer extension and DNA ligation assays. These results suggested that telbivudine functions as a chain terminator while entecavir was efficiently extended by the six enzymes and was a substrate for human DNA ligase I. Our findings suggested that incorporation of anti-HBV nucleotide analogs catalyzed by human X- and Y-family polymerases may contribute to clinical toxicity. PMID:22132702

Standardized Prevalence Ratios for Chronic Hepatitis C Virus Infection Among Adult Japanese Hemodialysis Patients

PubMed Central

Ohsawa, Masaki; Kato, Karen; Itai, Kazuyoshi; Tanno, Kozo; Fujishima, Yosuke; Konda, Ryuichiro; Okayama, Akira; Abe, Koichi; Suzuki, Kazuyuki; Nakamura, Motoyuki; Onoda, Toshiyuki; Kawamura, Kazuko; Sakata, Kiyomi; Akiba, Takashi; Fujioka, Tomoaki

2010-01-01

Background Many studies have estimated the prevalence of anti-hepatitis C virus (HCV) antibody among hemodialysis (HD) patients; however, the prevalence of HCV core antigen—which indicates the presence of chronic HCV infection—is not known. Methods Standardized prevalence ratios (SPRs) for anti-HCV antibody and HCV core antigen among HD patients (n = 1214) were calculated on the basis of data from the general population (n = 22 472) living in the same area. Results The prevalences of anti-HCV antibody and HCV core antigen were 12.5% and 7.8%, respectively, in male hemodialysis patients, and 8.5% and 4.1% in female hemodialysis patients. The SPRs (95% confidence interval) for anti-HCV antibody and HCV core antigen were 8.39 (6.72–10.1) and 12.9 (9.66–16.1), respectively, in males, and 5.42 (3.67–7.17) and 8.77 (4.72–12.8) in females. Conclusions The prevalences of chronic HCV infection among male and female HD patients were 13-fold and 9-fold, respectively, those of the population-based controls. Further studies should therefore be conducted to determine the extent of chronic HCV infection among HD patients in other populations and to determine whether chronic HCV infection contributes to increased mortality in HD patients. PMID:19881229

HD-03/ES: A Herbal Medicine Inhibits Hepatitis B Surface Antigen Secretion in Transfected Human Hepatocarcinoma PLC/PRF/5 Cells.

PubMed

Varma, Sandeep R; Sundaram, R; Gopumadhavan, S; Vidyashankar, Satyakumar; Patki, Pralhad S

2013-01-01

HD-03/ES is a herbal formulation used for the treatment of hepatitis B. However, the molecular mechanism involved in the antihepatitis B (HBV) activity of this drug has not been studied using in vitro models. The effect of HD-03/ES on hepatitis B surface antigen (HBsAg) secretion and its gene expression was studied in transfected human hepatocarcinoma PLC/PRF/5 cells. The anti-HBV activity was tested based on the inhibition of HBsAg secretion into the culture media, as detected by HBsAg-specific antibody-mediated enzyme assay (ELISA) at concentrations ranging from 125 to 1000  μ g/mL. The effect of HD-03/ES on HBsAg gene expression was analyzed using semiquantitative multiplex RT-PCR by employing specific primers. The results showed that HD-03/ES suppressed HBsAg production with an IC50 of 380  μ g/mL in PLC/PRF/5 cells for a period of 24 h. HD-03/ES downregulated HBsAg gene expression in PLC/PRF/5 cells. In conclusion, HD-03/ES exhibits strong anti-HBV properties by inhibiting the secretion of hepatitis B surface antigen in PLC/PRF/5 cells, and this action is targeted at the transcription level. Thus, HD-03/ES could be beneficial in the treatment of acute and chronic hepatitis B infections.

The Prevalence and Risk Factors for Hepatitis B Surface Ag Positivity in Pregnant Women in Eastern Region of Ghana

PubMed Central

Cho, Younmo; Bonsu, George; Akoto-Ampaw, Arko; Nkrumah-Mills, Grace; Nimo, Julia J.A.; Park, Jin Kyung

2012-01-01

Background/Aims The aim of this study was to evaluate the prevalence and risk factors for hepatitis B surface antigen (HBsAg) positivity in pregnant Ghanaian women. Methods We surveyed 1,500 pregnant women in Eastern region of Ghana. Direct interviews were performed by trained nurses using standardized questionnaires. Pregnant women were screened for human immunodeficiency virus (HIV) and hepatitis B infections, hemoglobin levels and sickle cell anemia as part of the antenatal check-up. Results The overall HBsAg positive rate was 10.6%, which varied among districts (13.8% for Kwahu West, 12.4% for Upper Manya, and 2.2% for Yilo Krobo). HBsAg positivity was significantly higher in women with depression (odds ratio [OR], 3.74; 95% confidence interval [CI], 2.13 to 6.57) and HIV (OR, 2.03; 95% CI, 1.06 to 3.89). Age, education, and gravidity were not related to HBsAg positivity. Anti-hepatitis B immunoglobulin for newborns of HBsAg-positive mothers is not provided at birth in public health facilities in Ghana. However, hepatitis B vaccination is provided as part of a routine vaccination schedule starting at 6 weeks of age. Conclusions To prevent mother-to-child transmission of hepatitis B, screening tests for HBsAg in pregnant women and hepatitis B vaccination of newborns immediately after birth need to be performed in this region. PMID:22570754

Simultaneous quantitation of two direct acting hepatitis C antivirals (sofosbuvir and daclatasvir) by an HPLC-UV method designated for their pharmacokinetic study in rabbits.

PubMed

Atia, Noha N; El-Shaboury, Salwa R; El-Gizawy, Samia M; Abo-Zeid, Mohammad Nabil

2018-05-22

Sofosbuvir (SOF) and daclatasvir (DCS) are novel, recently developed direct acting antiviral agents characterized by potent anti-hepatitis C virus action. A fast and efficient HPLC-UV method was developed, validated and applied for simultaneous determination of SOF and DCS in pharmaceutical formulations and biological fluids based on coupling liquid-liquid extraction with ultrasound and dual wavelength detection at λ max ; 260 and 313 nm for SOF and DCS, respectively. This approach provided simple, sensitive, specific and cost-effective determination of the SOF-DCS mixture with good recoveries of the analytes from plasma. Analytes were separated within 7 min on C 18 analytical column with acetonitrile-10 mM acetate buffer of pH 5.0 at a flow rate of 1.0 mL min -1 . The linear ranges were 1-20 μg mL -1 for SOF and 0.6-6 μg mL -1 for DCS with correlation coefficients ≥0.9995. The detection limits in spiked rabbit plasma were 0.20 and 0.19 μg mL -1 for SOF and DCS, respectively. The method was validated according to ICH and US-FDA guidelines. Finally, the method was successfully applied for simultaneous pharmacokinetic studies of SOF and DCS in rabbits using rofecoxib as internal standard. Copyright © 2018 Elsevier B.V. All rights reserved.

HIV and Hepatitis B Virus Coinfection: Approach to Management

PubMed Central

Chasan, Rachel; Reese, Lindsey; Fishbein, Dawn

2010-01-01

Objective To review diagnosis and treatment in patients with HIV and hepatitis B virus (HBV) coinfection. Methods Review of the literature in the context of a clinical case. Results All patients with HIV should be screened for the presence of coinfection with HBV. Following diagnosis with HBV infection, the level of HBV activity should be assessed with testing for HBeAg, HBV DNA, and potentially a biopsy for staging the degree of fibrosis present. Based on the results of this workup, a decision regarding the role of anti-hepatitis treatment should be made. According to the latest chronic hepatitis B and HIV treatment guidelines, coinfected patients who require treatment for chronic hepatitis B should be started on a regimen that is fully active against both HIV and HBV. A first-line regimen for coinfected patients is generally composed of tenofovir and emtricitabine, plus one other agent active against HIV. In coinfected patients, durable responses are rare, and therefore patients are usually required to remain on therapy indefinitely. Conclusion Intensification of surveillance techniques and education programs should be developed to help prevent transmission of infection and integrate coinfected patients into the health care system. Once engaged in care, coinfected patients should receive treatment for both HIV and chronic hepatitis B with the goal of a decrease in liver failure, cirrhosis, hepatocellular carcinoma, and chronic hepatitis B–related mortality. PMID:23761953

Long-Term Effectiveness of Accelerated Hepatitis B Vaccination Schedule in Drug Users

PubMed Central

Shah, Dimpy P.; Grimes, Carolyn Z.; Nguyen, Anh T.; Lai, Dejian

2015-01-01

Objectives. We demonstrated the effectiveness of an accelerated hepatitis B vaccination schedule in drug users. Methods. We compared the long-term effectiveness of accelerated (0–1–2 months) and standard (0–1–6 months) hepatitis B vaccination schedules in preventing hepatitis B virus (HBV) infections and anti-hepatitis B (anti-HBs) antibody loss during 2-year follow-up in 707 drug users (HIV and HBV negative at enrollment and completed 3 vaccine doses) from February 2004 to October 2009. Results. Drug users in the accelerated schedule group had significantly lower HBV infection rates, but had a similar rate of anti-HBs antibody loss compared with the standard schedule group over 2 years of follow-up. No chronic HBV infections were observed. Hepatitis C positivity at enrollment and age younger than 40 years were independent risk factors for HBV infection and antibody loss, respectively. Conclusions. An accelerated vaccination schedule was more preferable than a standard vaccination schedule in preventing HBV infections in drug users. To overcome the disadvantages of a standard vaccination schedule, an accelerated vaccination schedule should be considered in drug users with low adherence. Our study should be repeated in different cohorts to validate our findings and establish the role of an accelerated schedule in hepatitis B vaccination guidelines for drug users. PMID:25880946

Hepatocellular carcinoma developed in a living donor after left lobe donation: a case for caution.

PubMed

Ikegami, Toru; Yoshizumi, Tomoharu; Kawasaki, Junji; Shimagaki, Tomonari; Uchiyama, Hideaki; Soejima, Yuji; Maehara, Yoshihiko

2017-06-01

Although it has been recognized that those who are positive for anti-hepatitis B core antibody (anti-HBcAb) and negative for hepatitis B surface antigen (HBsAg) with normal liver function could be donors for living donor liver transplantation under appropriate prophylaxis, the negative impact of positive HBcAb on such donors themselves has not been reported. We present a case of a living donor with positive HBcAb, who donated his left lobe for his sister with unresectable giant hepatic hemangioma, and the donor himself developed a de novo hepatocellular carcinoma (HCC) 10 years after donation. He had been lost from the follow-up program since 1 year after donation. Imaging studies showed a heterogeneously enhanced mass compatible with HCC, which was 9 cm in size with portal invasion into the anterior portal vein of the remnant liver. Re-laparotomy for hepatectomy with the removal of the tumor thrombus in the anterior portal vein of the remnant liver was carried out, and he is free from recurrence 6 months after surgery on prophylactic sorafenib. At our institute, 58 (9.6%) donors among the 603 living donors were anti-HBcAb positive and anti-HBsAg negative, and we started regular HCC surveillance using sonogram every 6 months for these patients. © 2016 The Japan Society of Hepatology.

Phyllanthus Suppresses Prostate Cancer Cell, PC-3, Proliferation and Induces Apoptosis through Multiple Signalling Pathways (MAPKs, PI3K/Akt, NFκB, and Hypoxia).

PubMed

Tang, Yin-Quan; Jaganath, Indubala; Manikam, Rishya; Sekaran, Shamala Devi

2013-01-01

Phyllanthus is a traditional medicinal plant that has been found to have antihepatitis, antibacterial, and anticancer properties. The present studies were to investigate the in vitro molecular mechanisms of anticancer effects of Phyllanthus (P. amarus, P. niruri, P. urinaria, and P. watsonii) plant extracts in human prostate adenocarcinoma. The cancer ten-pathway reporter array was performed and revealed that the expression of six pathway reporters were significantly decreased (Wnt, NFκB, Myc/Max, hypoxia, MAPK/ERK, and MAPK/JNK) in PC-3 cells after treatment with Phyllanthus extracts. Western blot was conducted and identified several signalling molecules that were affected in the signalling pathways including pan-Ras, c-Raf, RSK, Elk1, c-Jun, JNK1/2, p38 MAPK, c-myc, DSH, β-catenin, Akt, HIF-1α, GSK3β, NFκB p50 and p52, Bcl-2, Bax, and VEGF, in treated PC-3 cells. A proteomics-based approach, 2D gel electrophoresis, was performed, and mass spectrometry (MS/MS) results revealed that there were 72 differentially expressed proteins identified in treated PC-3 cells and were involved in tumour cell adhesion, apoptosis, glycogenesis and glycolysis, metastasis, angiogenesis, and protein synthesis and energy metabolism. Overall, these findings suggest that Phyllanthus can interfere with multiple signalling cascades involved in tumorigenesis and be used as a potential therapeutic candidate for treatment of cancer.

A new strategy to identify hepatitis B virus entry inhibitors by AlphaScreen technology targeting the envelope-receptor interaction.

PubMed

Saso, Wakana; Tsukuda, Senko; Ohashi, Hirofumi; Fukano, Kento; Morishita, Ryo; Matsunaga, Satoko; Ohki, Mio; Ryo, Akihide; Park, Sam-Yong; Suzuki, Ryosuke; Aizaki, Hideki; Muramatsu, Masamichi; Sureau, Camille; Wakita, Takaji; Matano, Tetsuro; Watashi, Koichi

2018-06-22

Current anti-hepatitis B virus (HBV) agents have limited effect in curing HBV infection, and thus novel anti-HBV agents with different modes of action are in demand. In this study, we applied AlphaScreen assay to high-throughput screening of small molecules inhibiting the interaction between HBV large surface antigen (LHBs) and the HBV entry receptor, sodium taurocholate cotransporting polypeptide (NTCP). From the chemical screening, we identified that rapamycin, an immunosuppressant, strongly inhibited the LHBs-NTCP interaction. Rapamycin inhibited hepatocyte infection with HBV without significant cytotoxicity. This activity was due to impaired attachment of the LHBs preS1 domain to cell surface. Pretreatment of target cells with rapamycin remarkably reduced their susceptibility to preS1 attachment, while rapamycin pretreatment to preS1 did not affect its attachment activity, suggesting that rapamycin targets the host side. In support of this, a surface plasmon resonance analysis showed a direct interaction of rapamycin with NTCP. Consistently, rapamycin also prevented hepatitis D virus infection, whose entry into cells is also mediated by NTCP. We also identified two rapamycin derivatives, everolimus and temsirolimus, which possessed higher anti-HBV potencies than rapamycin. Thus, this is the first report for application of AlphaScreen technology that monitors a viral envelope-receptor interaction to identify viral entry inhibitors. Copyright © 2018 Elsevier Inc. All rights reserved.

In vitro and in vivo protein release and anti-ischemia/reperfusion injury properties of bone morphogenetic protein-2-loaded glycyrrhetinic acid-poly(ethylene glycol)-b-poly(l-lysine) nanoparticles

PubMed Central

Shan, Fang; Liu, YuJuan; Jiang, Haiying; Tong, Fei

2017-01-01

Here, we describe a bone morphogenetic protein-2 (BMP-2) nanocarrier based on glycyrrhetinic acid (GA)-poly(ethylene glycol) (PEG)-b-poly(l-lysine) (PLL). A protein nanocarrier was synthesized, characterized and evaluated as a BMP-2 delivery system. The designed nanocarrier was synthesized based on the ring-opening polymerization of amino acid N-carboxyanhydride. The final product was measured with 1H nuclear magnetic resonance. GA-PEG-b-PLL nanocarrier could combine with BMP-2 through electrostatic interaction to form polyion complex (PIC) micelles. BMP-2 could be rapidly and efficiently encapsulated through the GA-PEG-b-PLL nanocarrier under physiological conditions, exhibiting efficient encapsulation and sustained release. In addition, the GA-PEG-b-PLL-mediated BMP-2 delivery system could target the liver against hepatic diseases as it has GA-binding receptors. The anti-hepatic ischemia/reperfusion injury (anti-HI/RI) effect of BMP-2/GA-PEG-b-PLL PIC micelles was investigated in rats using free BMP-2 and BMP-2/PEG-b-PLL PIC micelles as controls, and the results showed that BMP-2/GA-PEG-b-PLL PIC micelles indicated significantly enhanced anti-HI/RI property compared to BMP-2 and BMP-2/PEG-b-PLL. All results suggested that GA-PEG-b-PLL could be used as a potential BMP-2 nanocarrier. PMID:29089759

A network pharmacology approach to discover active compounds and action mechanisms of San-Cao Granule for treatment of liver fibrosis

PubMed Central

Wei, Shizhang; Niu, Ming; Wang, Jian; Wang, Jiabo; Su, Haibin; Luo, Shengqiang; Zhang, Xiaomei; Guo, Yanlei; Liu, Liping; Liu, Fengqun; Zhao, Qingguo; Chen, Hongge; Xiao, Xiaohe; Zhao, Pan; Zhao, Yanling

2016-01-01

Ethnopharmacological relevance San-Cao Granule (SCG) has been used in patients with liver fibrosis for many years and has shown good effect. However, its mechanism of therapeutic action is not clear because of its complex chemical system. The purpose of our study is to establish a comprehensive and systemic method that can predict the mechanism of action of SCG in antihepatic fibrosis. Materials and methods In this study, a “compound–target–disease” network was constructed by combining the SCG-specific and liver fibrosis–specific target proteins with protein–protein interactions, and network pharmacology was used to screen out the underlying targets and mechanisms of SCG for treatment of liver fibrosis. Then, some key molecules of the enriched pathway were chosen to verify the effects of SCG on liver fibrosis induced by thioacetamide (TAA). Results This systematic approach had successfully revealed that 16 targets related to 11 SCG compounds were closely associated with liver fibrosis therapy. The pathway-enrichment analysis of them showed that the TGF-β1/Smad signaling pathway is relatively important. Animal experiments also proved that SCG could significantly ameliorate liver fibrosis by inhibiting the TGF-β1/Smad pathway. Conclusion SCG could alleviate liver fibrosis through the molecular mechanisms predicted by network pharmacology. Furthermore, network pharmacology could provide deep insight into the pharmacological mechanisms of Chinese herbal formulas. PMID:26929602

TALEN/CRISPR-mediated engineering of a promoterless anti-viral RNAi hairpin into an endogenous miRNA locus

PubMed Central

Senís, Elena; Mockenhaupt, Stefan; Rupp, Daniel; Bauer, Tobias; Paramasivam, Nagarajan; Knapp, Bettina; Gronych, Jan; Grosse, Stefanie; Windisch, Marc P.; Schmidt, Florian; Theis, Fabian J.; Eils, Roland; Lichter, Peter; Schlesner, Matthias; Bartenschlager, Ralf; Grimm, Dirk

2017-01-01

Successful RNAi applications depend on strategies allowing robust and persistent expression of minimal gene silencing triggers without perturbing endogenous gene expression. Here, we propose a novel avenue which is integration of a promoterless shmiRNA, i.e. a shRNA embedded in a micro-RNA (miRNA) scaffold, into an engineered genomic miRNA locus. For proof-of-concept, we used TALE or CRISPR/Cas9 nucleases to site-specifically integrate an anti-hepatitis C virus (HCV) shmiRNA into the liver-specific miR-122/hcr locus in hepatoma cells, with the aim to obtain cellular clones that are genetically protected against HCV infection. Using reporter assays, Northern blotting and qRT-PCR, we confirmed anti-HCV shmiRNA expression as well as miR-122 integrity and functionality in selected cellular progeny. Moreover, we employed a comprehensive battery of PCR, cDNA/miRNA profiling and whole genome sequencing analyses to validate targeted integration of a single shmiRNA molecule at the expected position, and to rule out deleterious effects on the genomes or transcriptomes of the engineered cells. Importantly, a subgenomic HCV replicon and a full-length reporter virus, but not a Dengue virus control, were significantly impaired in the modified cells. Our original combination of DNA engineering and RNAi expression technologies benefits numerous applications, from miRNA, genome and transgenesis research, to human gene therapy. PMID:27614072

Ursolic acid activates the apoptosis of prostate cancer via ROCK/PTEN mediated mitochondrial translocation of cofilin-1

PubMed Central

Mu, Dawei; Zhou, Gaobiao; Li, Jianye; Su, Bin; Guo, Heqing

2018-01-01

Ursolic acid has various pharmacological activities, and can reduce blood fat as well as having antihepatic, antitumoral, anti-inflammatory and antiviral properties. However, the pro-apoptotic mechanism by which ursolic acid influences human prostate cancer requires additional study. The aim of the present study was to assess whether ursolic acid activates the apoptosis of prostate cancer and to investigate the mechanism by which the Rho-associated protein kinase 1 (ROCK1)/phosphatase and tensin homolog (PTEN) signaling pathway performs a role in ursolic acid-mediated cofilin-1 to induce apoptosis in human prostate cancer. Firstly, the present study determined the pro-apoptotic mechanism by which ursolic acid influences the cell proliferation and apoptosis of human prostate LNCaP cancer cells. Caspase-3/9 activities and ROCK1, PTEN, Cofilin-1 and cytochrome c protein expression levels were also analyzed. In the present study, it is reported that the pro-apoptotic mechanism of ursolic acid potently suppressed the cell proliferation of human prostate LNCaP cancer cells. The present study revealed that the mediation of ROCK1/PTEN-cofilin-1/cytochrome c protein expression activates caspase-3/9 activities which subsequently induced the apoptosis of human prostate cancer cells. In conclusion, these findings demonstrated that ursolic acid activates the apoptosis of prostate cancer via ROCK/PTEN mediated cofilin-1/cytochrome c which mediated caspase-3/9 activities. PMID:29435058

Autologous blood donor screening indicated a lower prevalence of viral hepatitis in East vs West Germany: epidemiological benefit from established health resources.

PubMed

Wiegand, J; Luz, B; Mengelkamp, A-K; Moog, R; Koscielny, J; Halm-Heinrich, I; Susemihl, C; Bentzien, F; Diekmann, J; Wernet, D; Karger, R; Angert, K; Schmitt-Thomssen, A; Kiefel, V; Lutter, K; Hesse, R; Kätzel, R; Opitz, A; Luhm, J; Barz, D; Leib, U; Matthes, G; Tillmann, H L

2009-10-01

Prevalence data concerning viral hepatitis and human immunodeficiency virus (HIV) in the general population are usually scarce. We aimed for a large cohort representative of the general population that required little funding. Autologous blood donors are relatively representative of the general population, and are tested for viral hepatitis and HIV in many countries. However, frequently these data are not captured for epidemiologic purposes. We analysed data from well over 35,000 autologous blood donors as recorded in 21 different transfusion centres for anti-hepatitis C virus (HCV), HBsAg and anti-HIV, as well as TPHA if available. We found a lower prevalence of hepatitis B virus and HCV in East vs West Germany, 0.2%vs 0.32% and 0.16%vs 0.32% respectively, which confirms earlier data in smaller cohorts, thus supporting the value of our approach. HIV was too rare to disclose significant differences, 0.01%vs 0.02%. TPHA was higher in East (0.34%) vs West Germany (0.29%) without significant differences. HCV was more frequent in women vs men. Transfusion institutes managing autologous blood donations should be used as a resource for epidemiological data relating to viral hepatitis and HIV, if such testing is performed routinely. This approach generates data relating to the general population with special emphasis on undiagnosed cases.

Moderate Sustained Virologic Response Rates With 6-Week Combination Directly Acting Anti-Hepatitis C Virus Therapy in Patients With Advanced Liver Disease.

PubMed

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.

Biochemical Characterization of the Active Anti-Hepatitis C Virus Metabolites of 2,6-Diaminopurine Ribonucleoside Prodrug Compared to Sofosbuvir and BMS-986094

PubMed Central

Ehteshami, Maryam; Tao, Sijia; Ozturk, Tugba; Zhou, Longhu; Cho, Jong Hyun; Zhang, Hongwang; Amiralaei, Sheida; Shelton, Jadd R.; Lu, Xiao; Khalil, Ahmed; Domaoal, Robert A.; Stanton, Richard A.; Suesserman, Justin E.; Lin, Biing; Lee, Sam S.; Amblard, Franck; Whitaker, Tony; Coats, Steven J.

2016-01-01

Ribonucleoside analog inhibitors (rNAI) target the hepatitis C virus (HCV) RNA-dependent RNA polymerase nonstructural protein 5B (NS5B) and cause RNA chain termination. Here, we expand our studies on β-d-2′-C-methyl-2,6-diaminopurine-ribonucleotide (DAPN) phosphoramidate prodrug 1 (PD1) as a novel investigational inhibitor of HCV. DAPN-PD1 is metabolized intracellularly into two distinct bioactive nucleoside triphosphate (TP) analogs. The first metabolite, 2′-C-methyl-GTP, is a well-characterized inhibitor of NS5B polymerase, whereas the second metabolite, 2′-C-methyl-DAPN-TP, behaves as an adenosine base analog. In vitro assays suggest that both metabolites are inhibitors of NS5B-mediated RNA polymerization. Additional factors, such as rNAI-TP incorporation efficiencies, intracellular rNAI-TP levels, and competition with natural ribonucleotides, were examined in order to further characterize the potential role of each nucleotide metabolite in vivo. Finally, we found that although both 2′-C-methyl-GTP and 2′-C-methyl-DAPN-TP were weak substrates for human mitochondrial RNA (mtRNA) polymerase (POLRMT) in vitro, DAPN-PD1 did not cause off-target inhibition of mtRNA transcription in Huh-7 cells. In contrast, administration of BMS-986094, which also generates 2′-C-methyl-GTP and previously has been associated with toxicity in humans, caused detectable inhibition of mtRNA transcription. Metabolism of BMS-986094 in Huh-7 cells leads to 87-fold higher levels of intracellular 2′-C-methyl-GTP than DAPN-PD1. Collectively, our data characterize DAPN-PD1 as a novel and potent antiviral agent that combines the delivery of two active metabolites. PMID:27216050

Anti-hepatitis B virus (HBV) response of imiquimod based toll like receptor 7 ligand in hbv-positive human hepatocelluar carcinoma cell line.

PubMed

Das, Dipanwita; Sengupta, Isha; Sarkar, Neelakshi; Pal, Ananya; Saha, Debraj; Bandopadhyay, Manikankana; Das, Chandrima; Narayan, Jimmy; Singh, Shivaram Prasad; Chakrabarti, Sekhar; Chakravarty, Runu

2017-01-14

Toll like receptors (TLRs) play an important role in innate immunity and various studies suggest that TLRs play a crucial role in pathogenesis of hepatitis B virus (HBV) infection. The present study aims in looking into the status of crucial host and viral gene expression on inciting TLR7. The transcription of TLR7 pathway signaling molecules and HBV DNA viral load were quantified by Real Time-PCR after stimulation of TLR7 with its imiquimod based ligand, R837. Cell cycle analysis was performed using flow-cytometry. Expression of TLR7 and chief cell cycle regulator governing G1/S transition, p53 was also seen in liver biopsysss samples of CHB patients. HBV induced alteration in histone modifications in HepG2 cells and its restoration on TLR7 activation was determined using western blot. The TLR7 expression remains downregulated in HepG2.2.15 cells and in liver biopsy samples from CHB patients. Interestingly HBV DNA viral load showed an inverse relationship with the TLR7 expression in the biopsy samples. We also evaluated the anti-viral activity of R837, an agonist of TLR7. It was observed that there was a suppression of HBV replication and viral protein production upon TLR7 stimulation. R837 triggers the anti-viral action probably through the Jun N-terminal Kinase (JNK) pathway. We also observed a downregulation of histone H3K9Me3 repression mark upon R837 treatment in HBV replicating HepG2.2.15 cells, mimicking that of un-infected HepG2 cells. Additionally, the G1/S cell cycle arrest introduced by HBV in HepG2.2.15 cells was released upon ligand treatment. The study thus holds a close insight into the changes in hepatocyte micro-environment on TLR7 stimulation in HBV infection.

Immunogenicity of transgenic plant-derived hepatitis B surface antigen.

PubMed Central

Thanavala, Y; Yang, Y F; Lyons, P; Mason, H S; Arntzen, C

1995-01-01

The focus of the Children's Vaccine Initiative is to encourage the discovery of technology that will make vaccines more readily available to developing countries. Our strategy has been to genetically engineer plants so that they can be used as inexpensive alternatives to fermentation systems for production of subunit antigens. In this paper we report on the immunological response elicited in vivo by using recombinant hepatitis B surface antigen (rHBsAg) purified from transgenic tobacco leaves. The anti-hepatitis B response to the tobacco-derived rHBsAg was qualitatively similar to that obtained by immunizing mice with yeast-derived rHBsAg (commercial vaccine). Additionally, T cells obtained from mice primed with the tobacco-derived rHBsAg could be stimulated in vitro by the tobacco-derived rHBsAg, yeast-derived rHBsAg, and by a synthetic peptide that represents part of the a determinant located in the S region (139-147) of HBsAg. Further support for the integrity of the T-cell epitope of the tobacco-derived rHBsAg was obtained by testing the ability of the primed T cells to proliferate in vitro after stimulation with a monoclonal anti-idiotype and an anti-idiotype-derived peptide, both of which mimic the group-specific a determinant of HBsAg. In total, we have conclusively demonstrated that both B- and T-cell epitopes of HBsAg are preserved when the antigen is expressed in a transgenic plant. PMID:7724566

Effects and mechanisms of caffeine to improve immunological and metabolic abnormalities in diet-induced obese rats.

PubMed

Liu, Chih-Wei; Tsai, Hung-Cheng; Huang, Chia-Chang; Tsai, Chang-Youh; Su, Yen-Bo; Lin, Ming-Wei; Lee, Kuei-Chuan; Hsieh, Yun-Cheng; Li, Tzu-Hao; Huang, Shiang-Fen; Yang, Ying-Ying; Hou, Ming-Chih; Lin, Han-Chieh; Lee, Fa-Yauh; Lee, Shou-Dong

2018-05-01

In obesity, there are no effective therapies for parallel immune and metabolic abnormalities, including systemic/tissue insulin-resistance/inflammation, adiposity and hepatic steatosis. Caffeine has anti-inflammation, antihepatic steatosis, and anti-insulin resistance effects. In this study, we evaluated the effects and molecular mechanisms of 6 wk of caffeine treatment (HFD-caf) on immunological and metabolic abnormalities of high-fat diet (HFD)-induced obese rats. Compared with HFD vehicle (HFD-V) rats, in HFD-caf rats the suppressed circulating immune cell inflammatory [TNFα, MCP-1, IL-6, intercellular adhesion molecule 1 (ICAM-1), and nitrite] profiles were accompanied by decreased liver, white adipose tissue (WAT), and muscle macrophages and their intracellular cytokine levels. Metabolically, the increase in metabolic rates reduced lipid accumulation in various tissues, resulting in reduced adiposity, lower fat mass, decreased body weight, amelioration of hepatic steatosis, and improved systemic/muscle insulin resistance. Further mechanistic approaches revealed an upregulation of tissue lipogenic [(SREBP1c, fatty acid synthase, acetyl-CoA carboxylase)/insulin-sensitizing (GLUT4 and p-IRS1)] markers in HFD-caf rats. Significantly, ex vivo experiments revealed that the cytokine release by the cocultured peripheral blood mononuclear cell (monocyte) and WAT (adipocyte), which are known to stimulate macrophage migration and hepatocyte lipogenesis, were lower in HFD-V groups than HFD-caf groups. Caffeine treatment simultaneously ameliorates immune and metabolic pathogenic signals present in tissue to normalize immunolgical and metabolic abnormalities found in HFD-induced obese rats.

Hepatitis B vaccine booster dose: low-dose recombinant hepatitis B vaccines as a booster dose.

PubMed

Bryan, J P; MacArthy, P; Rudock, A; Fogarty, J P; Dowd, H; Legters, L J; Perine, P L

1997-06-01

The timing and best regimen for a booster dose of hepatitis B vaccine have not been determined. Two studies were conducted to determine the response to a booster dose of 5 micrograms recombinant hepatitis B vaccine. In the first study, a 5 micrograms (0.5 ml) dose of Recombivax HB was administered intramuscularly 38 months after the initial dose to 71 volunteers. In a second study, we offered a 5 micrograms dose recombinant hepatitis B vaccine, either Recombivax HB (0.5 ml) or Engerix B (0.25 ml), to students who had previously been immunized with three doses of vaccine. In the first study, among the 44 persons for whom postbooster sera were available, the geometric mean concentration of anti-hepatitis B surface antigens increased from 42 to 2090 mIU/ml after the 5 micrograms (0.5 ml) dose of Recombivax. In the second study, after a 5 micrograms (0.5 ml) dose of Recombivax, the geometric mean concentration increased from 43 to 990 mIU/ml (n = 48), and in the group that received a 5 micrograms (0.25 ml) dose of Engerix B, the concentration increased from 83 to 2337 mIU/ml (n = 45) (p = 0.18 for postdose concentrations). A 5 micrograms dose of recombinant vaccine results in an excellent booster response at a cost one fourth to one half that of a full 1 ml dose of vaccine.

Novel LAMP2 mutations in Chinese patients with Danon disease cause varying degrees of clinical severity.

PubMed

Luo, Su-shan; Xi, Jian-ying; Cai, Shuang; Zhao, Chong-bo; Lu, Jia-hong; Zhu, Wen-hua; Lin, Jie; Qiao, Kai; Wang, Yin; Ye, Zhu-rong

2014-01-01

Danon disease is an Xlinked dominant lysosomal glycogen storage disorder characterized by cardiomyopathy, skeletal myopathy, and mental retardation. This study described two Chinese cases of Danon disease in order to broaden the phenotypic and genetic spectrum. Clinical data were collected and LAMP2 mutations were analyzed. Patient A had fluctuating limb weakness during 6 months follow-up and was diagnosed with drug-induced myopathy due to anti-hepatitis B therapy with lamivudine. However, the first muscle biopsy with large cytoplasmic vacuoles confused the diagnosis and led to the second biopsy that allowed for the final diagnosis. Patient B had severe cardiac disturbances leading to sudden death. Molecularly, patient A harbored a synonymous mutation adjacent to the exon 6-intron 6 junction; mRNA analysis provided evidence that totally abolished the donor site and caused skipping of exon 6. Patient B harbored a frame-shift deletion mutation in exon 3 (c.396delA) leading to a truncated protein. To our knowledge, this is the first report of Danon disease caused by a synonymous exon mutation that affected mRNA splicing, which indicates that a synonymous substitution may not be silent when it is in the exon sequences close to the splice sites. It is also the first description of Danon disease clinically presenting as druginduced myopathy at onset; the pathological changes might be the key point for making a differential diagnosis. *These two authors contributed equally to this work.

Prevalence and associated factors of hepatitis C virus infection among renal disease patients on maintenance hemodialysis in three health centers in Aden, Yemen: a cross sectional study.

PubMed

Aman, Khadija; Al-Dubai, Sami AbdoRadman; Aman, Reema; Hawash, Aamenah; Alshagga, Mustafa; Kassim, Saba

2015-03-01

We aimed to assess the prevalence and factors associated with positive anti-hepatitis C virus (HCV) antibodies among patients on maintenance hemodialysis (HD) in three centers in Aden, Yemen. The data from 219 patients and their records over the period between 2000-2013, was extracted and analyzed. The mean ± SD age of the patients was 47.08 ± 13.9 years; 74.4% of them were married and 14.6% were employed. The prevalence of validated anti-HCV-positive cases was 40.2% (95%CI 33.64%-46.73%). The mean ± SD duration on HD of all the patients was 35.09 ± 38 months. On bivariate analysis, the duration on HD and attending more than one center for HD associated significantly with anti-HCV positivity (P <0.05). On multivariate fully adjusted Poisson regression modelling, controlled for age, Patients attending more than one center and those who underwent HD for longer durations were more likely to be positive for anti- HCV antibodies [P = 0.004, adjusted prevalence rate ratio (APRR) = 1.87, 95% confidence interval (CI): 1.22-2.88; P = 0.0005, APRR = 1.01, 95% CI: 1.00-1.02. In this study sample, the prevalence of HCV was significant. Patients attending more than one center and those who underwent HD for longer durations were found to be more likely to contract HCV. Enhancing existing infection control measures and allocating more resources to HD centers therefore warrants consideration.

Efficient HPTLC-dual wavelength spectrodensitometric method for simultaneous determination of sofosbuvir and daclatasvir: Biological and pharmaceutical analysis.

PubMed

Abo-Zeid, Mohammad Nabil; El-Gizawy, Samia M; Atia, Noha N; El-Shaboury, Salwa R

2018-05-01

Sofosbuvir (SOF) and daclatasvir (DCS) are newly discovered anti-hepatitis C drugs that have direct antiviral activity. A novel and simple high-performance thin-layer chromatography (HPTLC) method was designed for simultaneous determination of SOF and DCS in miscellaneous matrices. The method adopts coupling HPTLC with dual wavelength spectrodensitometry. Consequently, this enabled sensitive, specific and cost-effective determination of the SOF-DCS mixture. The developed HPTLC procedure is based on a simple liquid-liquid extraction, enrichment of the analytes and subsequent chromatographic separation with UV detection. Separations were performed on HPTLC silica gel 60 F 254 aluminum plates with a mobile phase consisting of ethyl acetate-isopropanol (85:15, v/v). Dual wavelength scanning was carried out in the absorbance mode at 265 and 311 nm for SOF and DCS, respectively. The linear ranges were 40-640 and 20-320 ng band -1 for SOF and DCS, respectively with correlation coefficients of ≥0.9997. The detection limits were 11.3 and 6.5 ng band -1 for SOF and DCS, respectively indicating high sensitivity of the proposed method. Consequently, this permits in vitro and in vivo application of the proposed method in human plasma with good percentage recovery (94.1-103.5%). Validation parameters were assessed according to ICH guidelines and US-FDA guidelines. Furthermore, the application was extended to analysis of SOF and DCS in their pharmaceutical formulations. Copyright © 2018 Elsevier B.V. All rights reserved.

Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Reveal Bradycardiac Effects Caused by Co-Administration of Sofosbuvir and Amiodarone.

PubMed

Yu, Yankun; Liu, Feng; He, Liuming; Ramakrishna, Seeram; Zheng, Monica; Bu, Lei; Xu, Ying

2018-05-30

Co-administration of sofosbuvir, an anti-hepatitis C virus medication, and antiarrhythmic amiodarone causes symptomatic severe bradycardia in patients and animal models. However, in a few in vitro studies, the combination of sofosbuvir and amiodarone resulted in tachycardiac effects in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). This discrepancy may be attributable to the use of immature hiPSC-CMs in the in vitro studies. To address this, we evaluated the ability of our in-house hiPSC-CMs to assess the interactions between sofosbuvir and amiodarone in vitro. We performed whole-cell patch recordings on hiPSC-CMs to examine the cardiac effect of sofosbuvir and amiodarone, alone or in combination. We found that sofosbuvir and amiodarone caused bradycardiac effects (the beating rate decreased to 75% of the vehicle control, P < 0.001) on our hiPSC-CMs when applied in combination, but they had no significant effect when applied alone. Furthermore, the bradycardiac effect was membrane potential dependent: it increased with depolarization. This raised the possibility that the bradycardiac effects in vivo may originate in nodal cells, which have a more depolarized resting membrane potential compared with ventricular cells. The bradycardiac effects of sofosbuvir plus amiodarone in vitro are consistent with the clinical phenotype and suggest that our hiPSC-CMs may serve as a useful tool in assessing cardiac safety during drug discovery and development process.

Discovery and structure-activity relationships study of thieno[2,3-b]pyridine analogues as hepatic gluconeogenesis inhibitors.

PubMed

Ma, Fei; Liu, Jian; Zhou, Tingting; Lei, Min; Chen, Jing; Wang, Xiachang; Zhang, Yinan; Shen, Xu; Hu, Lihong

2018-05-25

Type 2 diabetes mellitus (T2DM) is a chronic, complex and multifactorial metabolic disorder, and targeting gluconeogenesis inhibition is a promising strategy for anti-diabetic drug discovery. This study discovered a new class of thieno[2,3-b]pyridine derivatives as hepatic gluconeogenesis inhibitors. First, a hit compound (DMT: IC 50  = 33.8 μM) characterized by a thienopyridine core was identified in a cell-based screening of our privileged small molecule library. Structure activity relationships (SARs) study showed that replaced the CF 3 in the thienopyridine core could improve the potency and led to the discovery of 8e (IC 50  = 16.8 μM) and 9d (IC 50  = 12.3 μM) with potent inhibition of hepatic glucose production and good drug-like properties. Furthermore, the mechanism of 8e for the inhibition of hepatic glucose production was also identified, which could be effective through the reductive expression of the mRNA transcription level of gluconeogenic genes, including glucose-6-phosphatase (G6Pase) and hepatic phosphoenolpyruvate carboxykinase (PEPCK). Additionally, 8e could also reduce the fasting blood glucose and improve the oral glucose tolerance and pyruvate tolerance in db/db mice. The optimization of this class of derivatives had provided us a start point to develop new anti-hepatic gluconeogenesis agents. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Reappraisal of the Immunogenicity and Safety of Three Hepatitis A Vaccines in Adolescents.

PubMed

Yoon, Seo Hee; Kim, Han Wool; Ahn, Jong Gyun; Kim, In Tae; Kim, Jong-Hyun; Kong, Kyoung Ae; Kim, Kyung-Hyo

2016-01-01

Although the overall incidence of hepatitis A in Korea has been decreasing, adolescents remain highly vulnerable to its outbreaks. This study was conducted to compare the immunogenicity and safety of three hepatitis A vaccines in Korean adolescents. Healthy anti-hepatitis A virus seronegative subjects aged 13 to 19 yr were randomized in three equal groups to receive two doses of Avaxim™, Epaxal®, or Havrix®, 6 to 12 months apart. Seroconversion rates one month after the first dose were 98%, 95%, and 93% for Avaxim™, Epaxal®, and Havrix®, respectively. Seroconversion rates reached 100% for all vaccine groups one month after the second dose. Anti-HAV geometric mean concentrations (GMCs) were 7,207.7 mIU/mL (95% CI, 6023.1-8684.7), 1,750.5 mIU/mL (95% CI, 1362.9-2248.3), and 1,953.5 mIU/mL (95% CI, 1459.4-2614.7) after two doses of Avaxim™, Epaxal®, and Havrix® respectively. Avaxim™ was significantly more immunogenic than Epaxal® and Havrix®, whereas there were no significant differences in antibody responses between Epaxal® and Havrix®. Local and systemic solicited adverse events (AEs) were mostly of mild-to-moderate intensity and resolved within 5 days. No serious AEs were reported. In conclusion, all three vaccines are highly immunogenic and well-tolerated in Korean adolescents. (Clinical Trial Registry NCT00483470).

Quantitative hepatitis B core antibody levels in the natural history of hepatitis B virus infection.

PubMed

Song, L-W; Liu, P-G; Liu, C-J; Zhang, T-Y; Cheng, X-D; Wu, H-L; Yang, H-C; Hao, X-K; Yuan, Q; Zhang, J; Kao, J-H; Chen, D-S; Chen, P-J; Xia, N-S

2015-02-01

We previously demonstrated that pretreatment quantitative anti-hepatitis B core protein (qAnti-HBc) levels can predict the treatment response for both interferon and nucleoside analogue therapy, but the characteristics of qAnti-HBc during chronic hepatitis B virus (HBV) infection remain poorly understood. To understand this issue, the qAnti-HBc levels were evaluated in individuals with past HBV infection, occult HBV infection and chronic HBV infection in the immune tolerance phase, immune clearance phase, low-replicative phase and hepatitis B e antigen (HBeAg)-negative hepatitis phase. Individuals with hepatitis B surface antigen (n = 598, 3.74 ± 0.90 log10 IU/mL) had significantly higher (p < 0.001, approximately 1000-fold) serum qAnti-HBc levels than those who had occult HBV, and serum qAnti-HBc levels were significantly higher in the occult HBV group than in the past HBV infection group (p < 0.001). qAnti-HBc levels were positively correlated with alanine aminotransferase levels (R = 0.663, p < 0.001), and subjects with an abnormal alanine aminotransferase level had a higher qAnti-HBc level (p < 0.001). Serum qAnti-HBc level varied in different phases of HBV infection, as determined by host immune status. Serum qAnti-HBc level is strongly associated with hepatitis activity in subjects with chronic HBV infection. Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Study on four polymorphs of bifendate based on X-ray crystallography.

PubMed

Nie, Jinju; Yang, Dezhi; Hu, Kun; Lu, Yang

2016-05-01

Bifendate, a synthetic anti-hepatitis drug, exhibits polycrystalline mode phenomena with 2 polymorphs reported (forms A and B). Single crystals of the known crystalline form B and 3 new crystallosolvates involving bifendate solvated with tetrahydrofuran (C), dioxane (D), and pyridine (E) in a stoichiometric ratio of 1:1 were obtained and characterized by X-ray crystallography, thermal analysis, and Fourier transform infrared (FT-IR) spectroscopy. The differences in molecular conformation, intermolecular interaction and crystal packing arrangement for the four polymorphs were determined and the basis for the polymorphisms was investigated. The rotation of single bonds resulted in different orientations for the biphenyl, methyl ester and methoxyl groups. All guest solvent molecules interacted with the host molecule via an interesting intercalative mode along the [1 0 0] direction in the channel formed by the host molecules through weak aromatic stacking interactions or non-classical hydrogen bonds, of which the volume and planarity played an important role in the intercalation of the host with the guest. The incorporation of solvent-augmented rotation of the C-C bond of the biphenyl group had a striking effect on the host molecular conformation and contributed to the formation of bifendate polymorphs. Moreover, the simulated powder X-ray diffraction (PXRD) patterns for each form were calculated on the basis of the single-crystal data and proved to be unique. The single-crystal structures of the four crystalline forms are reported in this paper.

Establishment of hepatitis A detection antibodies set BRR batch 3 for antigen content determination by ELISA.

PubMed

Morgeaux, S; Manniam, I; Variot, P; Daas, A; Costanzo, A

2015-01-01

The current batch of the European Pharmacopoeia (Ph. Eur.) Biological Reference Reagents (BRRs) used for the in vitro potency assay of hepatitis A vaccines (HAV) by ELISA (enzymelinked immunosorbent assay) was established in 2012 for use in conjunction with Ph. Eur. general chapter 2.7.14 Assay of hepatitis A vaccine. It is composed of a coating reagent and a set of detection antibodies. As stocks of the latter are running low, the European Directorate for the Quality of Medicines & HealthCare (EDQM) organised a collaborative study to qualify replacement batches. The candidate BRR antibodies (primary monoclonal antibody and labelled secondary antibody) were prepared under appropriate conditions from starting materials similar to those used for the current batches. The new batches of antibodies were tested alongside previous batches of BRRs to ensure continuity, and the results confirmed that they were suitable for use in the potency assay of hepatitis A vaccines by ELISA using the standard method referenced in Ph. Eur. general chapter 2.7.14 at the same final concentrations as the previous batches, i.e. 1:500 for the primary monoclonal antibody and 1:400 for the secondary conjugated antibody. The outcome of the study allowed their establishment by the Ph. Eur. Commission in March 2015 as anti-hepatitis A virus primary detection antibody BRR batch 3 and conjugated secondary detection antibody BRR batch 3 respectively. They are available from the EDQM as hepatitis A vaccine ELISA detection antibodies set BRR batch 3.

A taxonomic revision of the subfamily Tillinae Leach sensu lato (Coleoptera, Cleridae) in the New World

PubMed Central

Burke, Alan; Zolnerowich, Gregory

2017-01-01

Abstract The subfamily Tillinae Leach is represented by 12 genera in the New World. In this study, eight of these genera are revised. A diagnosis and redescription of the species of Araeodontia Barr, Barrotillus Rifkind, Bogcia Barr, Cylidrus Latreille, Cymatoderella Barr, Lecontella Wolcott & Chapin, Monophylla Spinola, and Onychotillus Chapin are presented. Bogcia oaxacae Barr is designated as a junior synonym of Bogcia disjuncta Barr. One species, Cymatodera striatopunctata Chevrolat, is transferred to Lecontella. The following species are redescribed: Araeodontia isabellae (Wolcott), A. marginalis Barr, A. peninsularis (Schaeffer), Barrotillus kropotkini Rifkind, Bogcia disjuncta Barr, Cylidrus abdominalis Klug, Cymatoderella collaris (Spinola), C. morula Rifkind, C. patagoniae (Knull), Lecontella brunnea (Spinola), L. gnara Wolcott, L. striatopunctata (Chevrolat), Monophylla californica (Fall), M. pallipes Schaeffer, M. terminata (Say), Onychotillus vittatus Chapin, and O. cubana De Zayas. Transcriptions of the original descriptions of Araeodontia picipennis Barr, Bostrichoclerus bicornis Van Dyke and Monophylla cinctipennis (Chevrolat) are given. Cymatodera Gray, with approximately 130 described species, is excluded from this study due to the number of species involved. The genera Neocallotillus Burke and Callotillus Wolcott are also excluded here since these groups have been recently revised elsewhere. Collection data are provided for all species revised. Updated distribution maps are presented. Keys to New World genera and species are given and taxonomic characters of relevant importance are provided and discussed. PMID:29290697

Performance evaluation of four dominant anti-hepatitis B core antigen (HBcAb) kits in Japan for preventing de novo hepatitis B virus (HBV) infection.

PubMed

Kobayashi, Eiji; Deguchi, Matsuo; Kagita, Masanori; Yoshioka, Nori; Kita, Mifumi; Asari, Seishi; Suehisa, Etsuji; Hidaka, Yoh; Iwatani, Yoshinori

2015-01-01

The determination of antibody to hepatitis B core antigen (HBcAb) has become an important means of evaluating the risk factors of de novo hepatitis B virus (HBV) infection before starting intensive immunosuppressive drug therapies. Four dominant HBcAb determination reagents used in Japan were evaluated with HBcIgM, HBsAg, HBsAb, HBeAb, and HBV DNA reagents in order to study their clinical utility. Four kinds of HBcAb reagent kits (HBcAb Total and HBcAb-IgG reagent) were evaluated with 526 clinical specimens, including 344 negative specimens, at Osaka University Hospital. The dynamic range of each kit was evaluated by testing serially diluted serum from pooled sera with high HBcAb concentration. The reagent that showed the largest dynamic range was the Lumipulse HBcAb-N (HBcAb-IgG reagent). Regarding clinical sensitivity and specificity, Centaur HBcAb (HBcAb Total reagent) gave several "doubtful negative" results and ARCHITECT HBcII (HBcAb Total reagent) had the most discrepant positive results. By comparing the cut-off-index distribution of negative specimens using a parameter of "distance from the mean to the cut-off divided by the SD", Centaur was determined to be the best (distance/SD = 12.65), with Lumipulse and Elecsys Anti-HBc (HBcAb Total reagent) in the second group (8.13 and 7.00, respectively), and ARCHITECT rated as the worst (3.25). In this evaluation, Elecsys and Lumipulse HBcAb kits showed good clinical sensitivity and specificity and were considered to be suitable for evaluating the risk factors of de novo HBV infection.

Betulinic acid exerts anti-hepatitis C virus activity via the suppression of NF-κB- and MAPK-ERK1/2-mediated COX-2 expression.

PubMed

Lin, Chun-Kuang; Tseng, Chin-Kai; Chen, Kai-Hsun; Wu, Shih-Hsiung; Liaw, Chih-Chuang; Lee, Jin-Ching

2015-06-23

This study was designed to evaluate the effect of betulinic acid (BA), extracted from Avicennia marina, on the replication of hepatitis C virus (HCV) and to investigate the mechanism of this BA-mediated anti-HCV activity. HCV replicon and infectious systems were used to evaluate the anti-HCV activity of BA. Exogenous COX-2 or knock-down of COX-2 expression was used to investigate the role of COX-2 in the anti-HCV activity of BA. The effects of BA on the phosphorylation of NF-κB and on kinases in the MAPK signalling pathway were determined. The anti-HCV activity of BA in combination with other HCV inhibitors was also determined to assess its use as an anti-HCV supplement. BA inhibited HCV replication in both Ava5 replicon cells and in a cell culture-derived infectious HCV particle system. Treatment with a combination of BA and IFN-α, the protease inhibitor telaprevir or the NS5B polymerase inhibitor sofosbuvir resulted in the synergistic suppression of HCV RNA replication. Exogenous overexpression of COX-2 gradually attenuated the inhibitory effect of BA on HCV replication, suggesting that BA reduces HCV replication by suppressing the expression of COX-2. In particular, BA down-regulated HCV-induced COX-2 expression by reducing the phosphorylation of NF-κB and ERK1/2 of the MAPK signalling pathway. BA inhibits HCV replication by suppressing the NF-κB- and ERK1/2-mediated COX-2 pathway and may serve as a promising compound for drug development or as a potential supplement for use in the treatment of HCV-infected patients. © 2015 The British Pharmacological Society.

Hepatitis C Testing

PubMed Central

Rochlani, Maya; Lewis, Jessica H.; Ramsey, Glenn E.; Bontempo, Franklin A.; Shah, Gunjan; Bowman, Rebecca A.; van Thiel, David H.; Starzl, Thomas E.

2010-01-01

Plasma samples from 1,182 patients undergoing primary liver transplantation were tested for anti-hepatitis C (HCV) virus by two methods: Ortho HCV ELISA Test System (EIA) and Chiron RIBA HCV Test System (RIBA II). The EIA results, 0 or +, were recorded first, followed by RIBA results, N = negative, P = positive, or I = indeterminate. Concordant results—0N, + P, + I—were found in 1,076 (91%), and discordant results were found in 106 (9%). The EIA optical density did not relate to concordant or discordant results. Band patterns were described by stating the band position (1, 2, 3, or 4) and insetting a dash (−) if no band was visualized. Most + P samples fell into two patterns: 47% showed all four bands, pattern 1234, and 15% showed the two-band pattern, 34. When the EIA was negative, 0P, the opposite was seen: 8% showed the 1234 pattern and 81% showed the 34 pattern. There were 226 samples that formed bands (+ P, 149; 0P, 31; + I, 15; 0I, 31). The frequency of bands was as follows: 4, 32%; 3, 31%; 2, 19%; and 1, 18%. Band 2 and the EIA test detected antibodies to the same c100-3 fragment and showed 74% concordance. No explanation is apparent for the lower concordance rate here than that between the EIA test and bands 3 = 96% or 4 = 88%. The EIA and RIBA II tests, together with positive liver function tests and abnormal tissue pathologic findings, provide a basis for the diagnosis of HCV. PMID:1377442

Combined 3D-QSAR, molecular docking, molecular dynamics simulation, and binding free energy calculation studies on the 5-hydroxy-2H-pyridazin-3-one derivatives as HCV NS5B polymerase inhibitors.

PubMed

Yu, Haijing; Fang, Yu; Lu, Xia; Liu, Yongjuan; Zhang, Huabei

2014-01-01

The NS5B RNA-dependent RNA polymerase (RdRP) is a promising therapeutic target for developing novel anti-hepatitis C virus (HCV) drugs. In this work, a combined molecular modeling study was performed on a series of 193 5-hydroxy-2H-pyridazin-3-one derivatives as inhibitors of HCV NS5B Polymerase. The best 3D-QSAR models, including CoMFA and CoMSIA, are based on receptor (or docking). Furthermore, a 40-ns molecular dynamics (MD) simulation and binding free energy calculations using docked structures of NS5B with ten compounds, which have diverse structures and pIC50 values, were employed to determine the detailed binding process and to compare the binding modes of the inhibitors with different activities. On one side, the stability and rationality of molecular docking and 3D-QSAR results were validated by MD simulation. The binding free energies calculated by the MM-PBSA method gave a good correlation with the experimental biological activity. On the other side, by analyzing some differences between the molecular docking and the MD simulation results, we can find that the MD simulation could also remedy the defects of molecular docking. The analyses of the combined molecular modeling results have identified that Tyr448, Ser556, and Asp318 are the key amino acid residues in the NS5B binding pocket. The results from this study can provide some insights into the development of novel potent NS5B inhibitors. © 2013 John Wiley & Sons A/S.

Restorative effects of hydroxysafflor yellow A on hepatic function in an experimental regression model of hepatic fibrosis induced by carbon tetrachloride

PubMed Central

Li, Yanuo; Shi, Yan; Sun, Yan; Liu, Luying; Bai, Xianyong; Wang, Dong; Li, Hongxing

2017-01-01

Hepatic fibrosis is a reversible pathological process, in which fibrotic tissue is excessively deposited in the liver during the repair process that follows hepatic injury. Early prevention or treatment of hepatic fibrosis has great significance on the treatment of chronic hepatic diseases. Hydroxysafflor yellow A (HSYA) is a water-soluble monomer extracted from safflower, which serves numerous pharmacological roles. However, it remains to be elucidated how HSYA regulates hepatic fibrogenesis. The aim of the present study was to reveal the possible mechanisms underlying the effects of HSYA on the prevention and treatment of hepatic fibrosis. A rat model of hepatic fibrosis was established in the present study, and the rats were administered various doses of HSYA. The effects of HSYA on pathological alterations of the liver tissue in rats with hepatic fibrosis were observed using hematoxylin-eosin staining and Masson staining. In order to explore the anti-hepatic fibrosis effects and underlying mechanisms of HSYA, serum levels, and hepatic function and hepatic fibrosis indices were evaluated. The results demonstrated that HSYA can improve the general condition of rats with hepatic fibrosis and relieve cellular swelling of the liver, fatty degeneration, necrosis, inflammatory cell infiltration and fibroplastic proliferation. Subsequent to administration of HSYA, globulin was increased during hepatic fibrosis caused by tetrachloromethane. However, total cholesterol, triglyceride, alanine aminotransferase, aspartate aminotransferase and levels of hyaluronic acid, laminin, procollagen III N-terminal peptide, collagen type IV and hydroxyproline were significantly reduced. The results additionally demonstrated that HSYA could enhance superoxide dismutase activity and reduce malondialdehyde levels, inhibiting lipid peroxidation caused by free radicals. PMID:27909717

Detecting hepatitis B virus in surgical smoke emitted during laparoscopic surgery.

PubMed

Kwak, Han Deok; Kim, Seon-Hahn; Seo, Yeon Seok; Song, Ki-Joon

2016-12-01

Hepatitis B virus (HBV) transmission is known to occur through direct contact with infected blood. There has been some suspicion that the virus can also be detected in aerosol form. However, this has never been directly shown. The purpose of this study was to sample and analyse surgical smoke from laparoscopic surgeries on patients with hepatitis B to determine whether HBV is present. A total of 11 patients who underwent laparoscopic or robotic abdominal surgeries between October 2014 and February 2015 at Korea University Anam Hospital were included in this study. A high efficiency collector was used to obtain surgical smoke in the form of hydrosol. The smoke was analysed by using nested PCR. Robotic or laparoscopic colorectal resections were performed in 5 cases, laparoscopic gastrectomies in 3 cases and laparoscopic hepatic wedge resections in another 3 cases. Preoperatively, all of the patients had positive hepatitis B surface antigen (HBsAg). 2 patients had detectable HBsAb, and 2 were positive for hepatitis B e antigen. 3 patients were taking antihepatitis B viral medications at the time of the study. The viral load measured in the patients' blood was undetectable to 1.7×10 8  IU/mL. HBV was detected in surgical smoke in 10 of the 11 cases. HBV is detectable in surgical smoke. This study provides preliminary data in the investigation of airborne HBV infection. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Serological Tests Do Not Predict Residual Fibrosis in Hepatitis C Cirrhotics with a Sustained Virological Response to Interferon.

PubMed

D'Ambrosio, Roberta; Degasperi, Elisabetta; Aghemo, Alessio; Fraquelli, Mirella; Lampertico, Pietro; Rumi, Maria Grazia; Facchetti, Floriana; Grassi, Eleonora; Casazza, Giovanni; Rosenberg, William; Bedossa, Pierre; Colombo, Massimo

2016-01-01

Liver biopsy (LB) has lost popularity to stage liver fibrosis in the era of highly effective anti-hepatitis C virus (HCV) therapy, yet diagnosis of persistent cirrhosis may have important implications following HCV eradication. As performance of serological non-invasive tests (NITs) to predict residual fibrosis in non-viremic HCV patients is unknown, we investigated accuracy of NITs to predict residual fibrosis in cirrhotics after a sustained virological response (SVR) to interferon (IFN). Thirty-eight patients with a pre-treatment histological diagnosis of cirrhosis and a 48-104 months post-SVR LB were tested with APRI, CDS, FIB-4, FibroQ, Forns Score, GUCI Index, King Score, Lok Index, PLF, ELF. In 23 (61%) patients, cirrhosis had histologically regressed. All NITs values declined after SVR without any significant difference between regressors and non-regressors (AUROC 0.52-0.75). Using viremic cut-offs, PPV ranged from 34% to 100%, with lower NPV (63% - 68%). NITs performance did not improve using derived cut-offs (PPV: 40% - 80%; NPV: 66% - 100%). PLF, which combines several NITs with transient elastography, had the best diagnostic performance (AUROC 0.75, Sn 61%, Sp 90%, PPV 80%, NPV 78%). After treatment, none of the NITs resulted significantly associated with any of the histological features (activity grade, fibrosis stage, area of fibrosis). The diagnostic estimates obtained using both viremic and derived cut-off values of NITs were suboptimal, indicating that none of these tests helps predicting residual fibrosis and that LB remains the gold standard for this purpose.

[The Clinical Significance of Serum Alpha-fetoprotein in Diagnosing Hepatocellular Carcinoma in a Health Screening Population].

PubMed

Ko, Young Sun; Bae, Joo Hwan; Sinn, Dong Hyun; Gwak, Geum Youn; Kang, Wonseok; Paik, Yong Han; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon

2017-04-25

Serum alpha-fetoprotein (AFP) measurement is commonly included in a health check-up program in Korea. However, its benefits remain uncertain. We analyzed whether AFP measurement should be included in a general health check-up program to screen for hepatocellular carcinoma (HCC). A total of 36,552 adults aged 18 years or older-who participated in a routine health examination including AFP determination between January 2009 and December 2009 at the Health Promotion Center, Samsung Medical Center, South Korea-were analyzed. High risk of HCC was defined as positivity for hepatitis B surface antigen, anti-hepatitis C virus antibody or having liver cirrhosis. AFP level >10 ng/mL was observed in 27 participants (0.1%) and primary liver cancer was diagnosed in 9 patients (6 HCC and 3 cholangiocarcinoma). Among 1,619 participants with high risk factors of HCC, AFP level >10 ng/mL was observed in 16 participants, of which, 4 diagnoses were made. Sensitivity, specificity, positive predictive value, and negative predictive value of AFP for HCC was 0.66, 0.99, 0.25 and 0.99, respectively, for high risk participants. Among 34,933 participants without risk factors for HCC, 11 patients (<0.1%) showed elevated AFP levels above 10 ng/mL, and no case was diagnosed with primary liver cancer during a median follow-up period of 36 months (range: 0-48 months). AFP elevation was rare in participants without risk factors for HCC, and was unable to screen for HCC in this population. We discourage routine AFP measurements for asymptomatic adults without risk factors of HCC.

Introgression of Swertia mussotii gene into Bupleurum scorzonerifolium via somatic hybridization

PubMed Central

2011-01-01

Background The wild herb Swertia mussotii is a source of the anti-hepatitis compounds swertiamarin, mangiferin and gentiopicroside. Its over-exploitation has raised the priority of producing these compounds heterologously. Somatic hybridization represents a novel approach for introgressing Swertia mussotii genes into a less endangered species. Results Protoplasts derived from calli of Bupleurum scorzonerifolium and S. mussotii were fused to produce 194 putative hybrid cell lines, of which three (all derived from fusions where the S. mussotii protoplasts were pre-treated for 30 s with UV light) later differentiated into green plants. The hybridity of the calli was confirmed by a combination of isozyme, RAPD and chromosomal analysis. The hybrid calli genomes were predominantly B. scorzonerifolium. GISH analysis of mitotic chromosomes confirmed that the irradiation of donor protoplasts increased the frequency of chromosome elimination and fragmentation. RFLP analysis of organellar DNA revealed that mitochondrial and chloroplast DNA of both parents coexisted and recombined in some hybrid cell lines. Some of the hybrid calli contained SmG10H from donor, and produced swertiamarin, mangiferin and certain volatile compounds characteristic of S. mussotii. The expression of SmG10H (geraniol 10-hydroxylase) was associated with the heterologous accumulation of swertiamarin. Conclusions Somatic hybrids between B. scorzonerifolium and S. mussotii were obtained, hybrids selected all contained introgressed nuclear and cytoplasmic DNA from S. mussotii; and some produced more mangiferin than the donor itself. The introgression of SmG10H was necessary for the accumulation of swertiamarin. PMID:21513581

Risk factors for hospitalisation and associated costs among patients with hepatitis A associated with imported pomegranate arils, United States, 2013.

PubMed

Epson, E E; Cronquist, A; Lamba, K; Kimura, A C; Hassan, R; Selvage, D; McNeil, C S; Varan, A K; Silvaggio, J L; Fan, L; Tong, X; Spradling, P R

2016-07-01

To assess hospitalisation risk factors and economic effects associated with a multistate hepatitis A outbreak in 2013. Retrospective case series. Eligible outbreak-related cases confirmed by September 1, 2013, were defined as acute hepatitis symptoms and positive IgM anti-hepatitis A during March 15-August 12 among patients who consumed the food vehicle or had the outbreak genotype. We reviewed medical records, comparing demographic and clinical characteristics among hospitalized and non-hospitalized patients; we used logistic regression analysis to identify factors associated with hospitalization. We interviewed patients regarding symptom duration and healthcare usage and estimated per-patient and total costs. Health departments reported outbreak-related personnel hours. Medical records were reviewed for 147/159 (92%) eligible patients; median age was 48 (range: 1-84) years, and 64 (44%) patients were hospitalized. Having any chronic medical condition was independently associated with hospitalisation (odds ratio, 3.80; 95% confidence interval, 1.68-8.62). Interviews were completed for 114 (72%) eligible patients; estimated per-patient cost of healthcare and productivity loss was $13,467 for hospitalized and $2138 for non-hospitalized patients and $1,304,648 for all 165 outbreak-related cases. State and local public health personnel expenditures included 82 h and $3221/outbreak-related case. Hospitalisations in this outbreak were associated with chronic medical conditions and resulted in substantial healthcare usage and lost productivity. These data can be used to inform future evaluation of expansion of hepatitis A vaccination recommendations to include adults with chronic medical conditions. Published by Elsevier Ltd.

[The use of chest X-rays for surveillance of bacterial pneumonias in children in Latin America].

PubMed

Lagos, Rosanna; di Fabio, José Luis; Moënne, Karla; Muñoz M, Alma; Wasserman, Steven; de Quadros, Ciro

2003-05-01

The Division of Vaccines and Immunization of the Pan American Health Organization (PAHO) is promoting epidemiological surveillance of bacterial pneumonias in children in Latin America in order to generate scientific evidence to support future decisions concerning using vaccines to control such pneumonias in the countries of the Region of the Americas. The diagnosis of these diseases rarely includes bacteriological documentation of the causative agent. Therefore, studies of this type that are carried out around the world accept radiological images of alveolar consolidation as a confirmatory criterion for a presumptively bacterial pneumonia. This piece examines the theoretical rationale and requirements for using thorax radiology as an instrument for epidemiological surveillance of bacterial pneumonias. The piece also summarizes the activities carried out during 2 years of joint efforts between the Center for Vaccine Development (Centro para Vacunas en Desarrollo) of Chile and PAHO's Division of Vaccines and Immunization. During those 2 years, the two groups encouraged the epidemiological study of bacterial pneumonias in Latin American children, using internationally accepted criteria and definitions as well as tools and practical solutions adapted to the reality of the Region of the America. The activities carried out so far show both the need for and the feasibility of standardizing the interpretation of chest radiographs so that they can be used in epidemiological studies.

Decrease in seroprevalence of hepatitis A after the implementation of nationwide disposable tableware use in Taiwan.

PubMed

Su, Shih-Bin; Lin, Ching-Yih; Sheu, Ming-Jen; Kan, Wei-Chih; Wang, Hsien-Yi; Guo, How-Ran

2010-11-23

Taiwan is an endemic area of viral hepatitis, including hepatitis A, which is transmitted mainly from the fecal-oral route. In order to reduce the transmission through food intake, the government implemented a policy of nationwide disposal tableware use in public eating places in 1982. We conducted a study to estimate the seroprevalence of Hepatitis A in a group of workers in Taiwan in 2005, determine the risk factors, and compare seroprevalence to published estimates in Taiwan to evaluate changes in the seroprevalence after the implementation of the nationwide disposal tableware use. We recruited workers of an industrial park during their annual health examinations in 2005 and measured their anti-hepatitis A virus IgG titer using microparticle enzyme immunoassay. We compared the seroprevalence across different birth cohorts within the study population and also analyzed data from previous studies. The overall sero-positive rate was 22.0% in the 11,777 participants. The rate was much lower among those who were covered by the program since birth (born after 1982) in comparison with those who were not (2.7% vs. 25.3%, p < 0.001). From the analyses of data from previous studies, we found the age-specific rates were similar in cohorts born in or after 1982 across studies conducted in different time periods but decreased with the calendar year in cohorts born before 1982. In particular, the age-specific seroprevalence dropped to less than one third in a three-year period among those who were born around 1982. Data from both the current and previous studies in different time periods supported the effectiveness of disposal tableware in preventing the transmission of hepatitis A.

Serologic assessment of type 1 and type 2 immunity in healthy Japanese adults.

PubMed

Birmann, Brenda M; Mueller, Nancy; Okayama, Akihiko; Hsieh, Chung-Cheng; Tachibana, Nobuyoshi; Tsubouchi, Hirohito; Lennette, Evelyne T; Harn, Donald; Stuver, Sherri

2004-08-01

We assessed the informativeness of several serologic biomarkers of immune function using serum specimens collected in the Miyazaki Cohort Study from subjects who were seronegative for anti-human T-cell lymphotrophic virus I and anti-hepatitis C virus. To broadly characterize type 1 immune status, we measured EBV antibody titers, because titer profiles associated with cellular immune suppression are well described. We also tested for three type 2 biomarkers: total serum IgE, soluble CD23, and soluble CD30. Nonreactivity to a tuberculin purified protein derivative (PPD) skin test is indicative of diminished delayed-type hypersensitivity (type 1) responsiveness in the study population due to a history of tuberculosis exposure or Bacillus Calmette-Guérin vaccination. We therefore evaluated the serologic markers as predictors of PPD nonreactivity using logistic regression. Subjects whose EBV antibody profiles were consistent with deficient type 1 immunity were more than thrice as likely to be PPD nonreactive as persons with "normal" antibody titers. Elevated total IgE was also strongly associated with PPD nonreactivity (odds ratio 3.4, 95% confidence interval 1.2-9.9); elevated soluble CD23 had a weaker, but positive, odds ratio, whereas soluble CD30 levels were not predictive of PPD status. Therefore, PPD nonreactivity is associated, in this population, with a pattern of serum biomarkers that is indicative of diminished type 1 and elevated type 2 immunity. We conclude that, with the exception of soluble CD30, the serologic markers are informative for the characterization of type 1/type 2 immune status using archived sera from study populations of healthy adults.

Antiviral Activity of Glycyrrhizin against Hepatitis C Virus In Vitro

PubMed Central

Matsumoto, Yoshihiro; Matsuura, Tomokazu; Aoyagi, Haruyo; Matsuda, Mami; Hmwe, Su Su; Date, Tomoko; Watanabe, Noriyuki; Watashi, Koichi; Suzuki, Ryosuke; Ichinose, Shizuko; Wake, Kenjiro; Suzuki, Tetsuro; Miyamura, Tatsuo; Wakita, Takaji; Aizaki, Hideki

2013-01-01

Glycyrrhizin (GL) has been used in Japan to treat patients with chronic viral hepatitis, as an anti-inflammatory drug to reduce serum alanine aminotransferase levels. GL is also known to exhibit various biological activities, including anti-viral effects, but the anti-hepatitis C virus (HCV) effect of GL remains to be clarified. In this study, we demonstrated that GL treatment of HCV-infected Huh7 cells caused a reduction of infectious HCV production using cell culture-produced HCV (HCVcc). To determine the target step in the HCV lifecycle of GL, we used HCV pseudoparticles (HCVpp), replicon, and HCVcc systems. Significant suppressions of viral entry and replication steps were not observed. Interestingly, extracellular infectivity was decreased, and intracellular infectivity was increased. By immunofluorescence and electron microscopic analysis of GL treated cells, HCV core antigens and electron-dense particles had accumulated on endoplasmic reticulum attached to lipid droplet (LD), respectively, which is thought to act as platforms for HCV assembly. Furthermore, the amount of HCV core antigen in LD fraction increased. Taken together, these results suggest that GL inhibits release of infectious HCV particles. GL is known to have an inhibitory effect on phospholipase A2 (PLA2). We found that group 1B PLA2 (PLA2G1B) inhibitor also decreased HCV release, suggesting that suppression of virus release by GL treatment may be due to its inhibitory effect on PLA2G1B. Finally, we demonstrated that combination treatment with GL augmented IFN-induced reduction of virus in the HCVcc system. GL is identified as a novel anti-HCV agent that targets infectious virus particle release. PMID:23874843

The Correlation between Different Risk Factors of Hepatitis C and Different Genotypes

PubMed Central

Mokhtari, Mozhgan; Basirkazeruni, Hanieh; Rostami, Mojtaba

2017-01-01

Background: Hepatitis C infection is one of the health problems in the world. Several known risk factors are responsible in transmission of this infection. We are going to study the prevalence of these risk factors for different genotypes of hepatitis C and if possible, specify probable relations between each risk factor and transmission of each genotype. Materials and Methods: This is a cross-sectional study done on 270 people who had positive anti-hepatitis C virus (HCV) antibody and HCV RNA. Demographic specificity and possible risk factors were collected using a questionnaire, and statistical analysis was done by SPSS software (version 20). Chi-square test used to estimate the prevalence and relation between each qualitative risk factor and HCV genotype transmitted. Analysis of variance was used for studying the prevalence and relation between quantitative risk factors and HCV genotypes. Results: The sample size was 270 persons. Of these, 217 (80.4%) were men and 185 (68.5%) were infected with genotype Type III. Most people were in age range of 31–40 years old 92 (34%). Single people were 126 (46.7%) and 169 (62.6%) were high school and university graduated. Tattooing as a risk factor had a meaningful relation with hepatitis C genotype (P < 0.001). Conclusions: According to the findings, most people in central provinces of Iran with hepatitis C are carrying genotype III, with most prevalent risk factors such as intravenous drug use and unsafe sexual activity. Besides, tattooing had a significant association with hepatitis C genotype, so that in these groups of people, genotype I was more frequent isolated virus. PMID:28503500

[Prevalence of and risk factors for hepatitis C in blood donors].

PubMed

Ladrón-de Guevara, Laura; Gómez, Nicolás; Vázquez-Cantarell, Mariana; García-Méndez, Sergio; Di Silvio, Mauricio

2002-01-01

Determine hepatitis C prevalence and risk factors in blood donors from the Blood Bank at the Centro Médico Nacional 20 de Noviembre ISSSTE, in Mexico City. A total of 41,957 blood donors were included in the study was done from January 1996 to August 2000. To study risk factors, a case-control study cases were defined as blood donors with repeatedly positive anti-hepatitis C virus (HCV) ELISA test. Controls were defined as blood donors with negative anti-HCV ELISA test. All cases were interviewed a second time on HCV infection-associated risk factors. Odd ratio (OR) and confidence interval 95% (CI 95%) were calculated for each risk factoring in a univariate analysis. Multivariate analysis was performed subsequents to determine the independent contribution or each risk factor. HCV crude total prevalence was 0.84%. Risk factors were found in 36.16% anti-HCV-positive blood donors. During the second interview, 30% of sero-positive blood donors recalled one or more risk factors they previously denied. The most important risk factors, found were as follows sexual relations with prostitutes (OR 7.48, CI 95% 1.43-38.92) transfusion (OR 6, CI 95% 2.62-13.72); nasal cocaine use (OR 8.89, CI 95%, 1.01-86.89); dental surgery (OR 8.89, CI 95% 1.01-86.89) and contact with hepatitis-infected subject (OR 3.01, CI 95% 1.17-7.70). Other risk factors did not show a significant association. In this study, we found a crude total prevalence of 0.84%, very close to the prevalence reported in Mexican population by the National Center for Blood Transfusion.

Occult hepatitis B virus infection of hemodialysis patients: a cross-sectional study in a hepatitis B virus-endemic region.

PubMed

Kim, So Mi; Kim, Hyun Woo; Lee, Ji Eun; Lee, Eun Kyoung; Shin, Hyun Deok; Song, Il Han

2015-01-01

Occult hepatitis B virus (HBV) infection is defined as the presence of HBV DNA in the liver tissue and/or serum of subjects seronegative for hepatitis B surface antigen (HBsAg). Occult HBV infection of hemodialysis (HD) patients is informative in terms of virus transmission, reactivation after kidney transplantation, and the progression of liver disease. However, there is little detailed information about occult HBV infection in the context of virus endemicity. We tried to investigate the seroprevalence and clinical features of occult HBV infection in HD patients in HBV-endemic regions. We enrolled a total of 159 HD patients and 121 apparently healthy subjects at Dankook University Hospital and Jeju National University Hospital in Korea. HBsAg, anti-HBs, anti-HBc, and anti-hepatitis C virus (HCV) antibody levels were measured by radioimmunoassay. Serum levels of HBV DNA were measured by real-time polymerase chain reaction. The seroprevalence of occult HBV infection was 1.3% in HD patients and 2.5% in the healthy controls. This difference was not significant. The HBV load in all subjects with occult infection was <116 copies/mL, and all were positive for IgG anti-HBc, regardless of the presence of anti-HBs. None of the occult HBV-infected subjects were co-infected with HCV. One of the 2 HD patients with occult HBV infection had no history of blood transfusion. In this HBV-endemic region, the seroprevalence of occult HBV infection in HD patients with a very low viral load was not significantly different from that in apparently healthy subjects. © 2014 International Society for Hemodialysis.

Evaluation of the VIDAS Anti-HCV Assay for Detection of Hepatitis C Virus Infection.

PubMed

Hyun, Jungwon; Ko, Dae Hyun; Kang, Hee Jung; Whang, Dong Hee; Cha, Young Joo; Kim, Hyun Soo

2016-11-01

Anti-hepatitis C virus antibody (anti-HCV) assays are recommended for screening HCV-infected persons. The VIDAS Anti-HCV Assay (bioMérieux, France), based on the enzyme-linked fluorescence test principle, was recently introduced in Korea. We evaluated the clinical performance of the VIDAS assay. One hundred HCV-positive and 1,002 HCV-negative blood samples confirmed by Architect anti-HCV (Abbott Laboratories, USA) and COBAS TaqMan HCV real-time PCR (Roche Diagnostics, USA) or the Procleix Ultrio Plus Assay (Gen-Probe Incorporated, USA) were obtained from the Human Serum Bank (HSB) and tested by VIDAS. In case of discrepant results, we conducted a recombinant immunoblot assay (RIBA). The agreement rates for known HCV-positive and HCV-negative samples between the VIDAS assay and the HSB testing were 100% (95% confidence interval [CI]: 96.4-100%) and 99.5% (95% CI: 98.8-99.8%), respectively. One of the five discrepant samples was positive for Core 2+ and NS3-2 2+ reactivity, two samples were negative, and the other two were indeterminate regarding NS4 2+ reactivity in RIBA. We observed a significant but weak positive correlation between the titers of VIDAS and Architect assays (r=0.315, P<0.001). The VIDAS anti-HCV assay, developed on the VIDAS automated immunoassay platform based on the ready-to-use, single-sample test concept may be useful in small-to-medium-sized laboratories. It showed good agreement with Architect anti-HCV and COBAS PCR assays and is therefore useful for detection of HCV infection. Weakly test-positive (ambiguous) samples require additional testing by another anti-HCV, RIBA, or HCV RNA assay.

Evaluation of the VIDAS Anti-HCV Assay for Detection of Hepatitis C Virus Infection

PubMed Central

Hyun, Jungwon; Ko, Dae-Hyun; Kang, Hee Jung; Whang, Dong Hee

2016-01-01

Background Anti-hepatitis C virus antibody (anti-HCV) assays are recommended for screening HCV-infected persons. The VIDAS Anti-HCV Assay (bioMérieux, France), based on the enzyme-linked fluorescence test principle, was recently introduced in Korea. We evaluated the clinical performance of the VIDAS assay. Methods One hundred HCV-positive and 1,002 HCV-negative blood samples confirmed by Architect anti-HCV (Abbott Laboratories, USA) and COBAS TaqMan HCV real-time PCR (Roche Diagnostics, USA) or the Procleix Ultrio Plus Assay (Gen-Probe Incorporated, USA) were obtained from the Human Serum Bank (HSB) and tested by VIDAS. In case of discrepant results, we conducted a recombinant immunoblot assay (RIBA). Results The agreement rates for known HCV-positive and HCV-negative samples between the VIDAS assay and the HSB testing were 100% (95% confidence interval [CI]: 96.4-100%) and 99.5% (95% CI: 98.8-99.8%), respectively. One of the five discrepant samples was positive for Core 2+ and NS3-2 2+ reactivity, two samples were negative, and the other two were indeterminate regarding NS4 2+ reactivity in RIBA. We observed a significant but weak positive correlation between the titers of VIDAS and Architect assays (r=0.315, P<0.001). Conclusions The VIDAS anti-HCV assay, developed on the VIDAS automated immunoassay platform based on the ready-to-use, single-sample test concept may be useful in small-to-medium-sized laboratories. It showed good agreement with Architect anti-HCV and COBAS PCR assays and is therefore useful for detection of HCV infection. Weakly test-positive (ambiguous) samples require additional testing by another anti-HCV, RIBA, or HCV RNA assay. PMID:27578508

Retrospective investigation of patients exposed to possible transmission of hepatitis C virus by a capillary blood glucose meter.

PubMed

Kadi, Z; Saint-Laurent, P; Cadranel, J F; Joly, C; Dumouchel, P; Jeanne, S; Thiers, V; Ciurana, O; Astagneau, P

2006-05-01

A 75-year-old female with no known risk factors for hepatitis C virus (HCV) infection was hospitalized and a diagnosis of HCV seroconversion was established (HCV immunoblot and a positive quantitative viral load). An epidemiological investigation revealed that, during a previous hospitalization resulting in a diagnosis of diabetes, she had shared a Glucotrend capillary blood glucose meter (CBGM; Roche Diagnostics, France) with a known HCV-positive diabetic patient. Poor hygiene practices were observed when using this device. Since the Glucotrend CBGM had been purchased, the suspected source patient had been hospitalized eight times and another 19 diabetic patients with known anti-HCV antibodies also regularly attended the same hospital. Consequently, 35 diabetic patients who had been hospitalized at the same time as the suspected source patient and 1305 patients who had used the Glucotrend CBGM were invited to undergo serum anti-hepatitis B virus, anti-HCV and anti-human immunodeficiency virus testing. Among the 35 diabetic patients, none of the 24 subjects tested were positive. Among the 1305 other patients, 995 were tested and 19 (2%) were anti-HCV positive. Although this prevalence is higher than that reported in the general French population, this excess risk cannot be attributed to use of the CBGM. Furthermore, molecular analysis showed that the two HCV strains isolated did not belong to the same phylogenetic cluster. However, as a result of this incident, measures were taken to minimize the transmission of bloodborne viruses in the hospital concerned. Other French hospitals were informed by a national alert message from the French Agency for the Safety of Health Products.

Clinicopathological features of liver injury in patients with type 2 diabetes mellitus and comparative study of histologically proven nonalcoholic fatty liver diseases with or without type 2 diabetes mellitus.

PubMed

Shima, Toshihide; Uto, Hirofumi; Ueki, Kohjiro; Takamura, Toshinari; Kohgo, Yutaka; Kawata, Sumio; Yasui, Kohichiroh; Park, Hyohun; Nakamura, Naoto; Nakatou, Tatsuaki; Tanaka, Nobuyoshi; Umemura, Atsushi; Mizuno, Masayuki; Tanaka, Junko; Okanoue, Takeshi

2013-04-01

The Japan Society of Diabetes Mellitus reported that the leading cause of death in patients with diabetes mellitus (DM) was chronic liver disease; however, there are limited studies investigating the cause of liver injury in these patients. Our study aimed to clarify the clinicopathological features of liver injury and the characteristics of nonalcoholic fatty liver disease (NAFLD) in DM patients. In total, 5,642 DM patients and 365 histologically proven NAFLD patients were enrolled. Clinical and laboratory parameters and liver biopsy results were, respectively, recorded and analyzed for the two sets of patients. Positivity rates for Hepatitis B surface antigens (HBsAg) and anti-hepatitis C virus antibodies (anti-HCV Ab) were 1.7 and 5.1 %, respectively. The proportion of drinkers consuming 20-59 g and ≥60 g alcohol daily was 14.9 and 4.3 %, respectively. The percentage of DM patients with elevated serum alanine aminotransferase (ALT) levels (≥31 IU/L) was 28.6 %. Alcohol consumption had no significant effect on serum ALT levels. Seventy-two percent of HBsAg-positive patients were serum hepatitis B virus (HBV)-DNA negative, whereas 10 % exhibited high levels of the same (>4.0 log copies/ml). Thirty-eight percent of anti-HCV Ab-positive patients were serum HCV-RNA negative. Among the NAFLD patients, the frequencies of NASH and advanced stage NASH were significantly higher in male DM patients than in male patients without DM. Although HBsAg- and anti-HCV Ab-positivity rates were high in our Japanese DM patients, a majority of liver injuries could be associated with NAFLD/nonalcoholic steatohepatitis.

Low incidence of hepatitis B virus reactivation and subsequent hepatitis in patients with chronic hepatitis C receiving direct-acting antiviral therapy.

PubMed

Tamori, A; Abiru, S; Enomoto, H; Kioka, K; Korenaga, M; Tani, J; Enomoto, M; Sugiyama, M; Masaki, T; Kawada, N; Yatsuhashi, H; Nishiguchi, S; Mizokami, M

2018-05-01

To determine the clinical characteristics of hepatitis B virus (HBV) reactivation in patients undergoing interferon-free antihepatitis C virus (HCV) therapy, we examined HBV DNA in 25 HBV co-infected patients and 765 patients with resolved HBV infection during and after treatment with direct-acting antiviral agents (DAAs). Among those with HCV genotype 1, asunaprevir plus daclatasvir was administered to 160 patients, sofosbuvir (SOF) plus ledipasvir to 438 patients and paritaprevir plus ombitasvir and ritonavir to 25 patients. In total, 167 patients with genotype 2 were treated with SOF plus ribavirin. Three patients with an HBV DNA level ≥2000 IU/mL were treated with entecavir before anti-HCV therapy, without reactivation of HBV. In 3 of 22 (12%) HBV surface antigen (HBsAg)-positive patients with an HBV DNA level <2000 IU/mL, the viral load increased during treatment. However, hepatitis flare did not occur in these patients. There was no significant difference in clinical history between patients with and without HBV reactivation. Among 765 patients with resolved HBV infection, HBV reactivation occurred in 1 (0.1%) patient after initial resolution, whose HBV DNA level spontaneously decreased after DAA therapy. We compared anti-HBs titres at baseline with those at post-DAA therapy in 123 patients without HBsAg. There was no significant difference in anti-HBs levels between the two points (P = .79). In conclusion, HBV reactivation was rare in HBsAg-negative patients treated with DAA therapy. Additionally, hepatitis did not occur in HBV-reactivated patients with a baseline HBV DNA level <2000 IU/mL before DAA therapy. © 2017 John Wiley & Sons Ltd.

Distinct features in natural history and outcomes of acute hepatitis C.

PubMed

Bunchorntavakul, Chalermrat; Jones, Lisa M; Kikuchi, Masahiro; Valiga, Mary E; Kaplan, David E; Nunes, Frederick A; Aytaman, Ayse; Reddy, K Rajender; Chang, Kyong-Mi

2015-04-01

Acute hepatitis C (AHCV) provides a diagnostic challenge with diverse clinical presentations. This study was aimed to examine the clinical and demographic features as well as outcomes in AHCV patients identified from inpatient and outpatient hospital settings. Patients with suspected AHCV were recruited from Philadelphia VA Medical Center, Hospital of University of Pennsylvania and Brooklyn VA Medical Center between 2000 and 2010. AHCV was diagnosed by acute serum alanine aminotransferase elevation with anti-hepatitis C virus (HCV) seroconversion, HCV-RNA fluctuations above 1 log, and/or recent high-risk exposure without prior HCV infection, excluding those with human immunodeficiency virus infection. Clinical and therapeutic outcomes were monitored for at least 6 months. A total of 40 AHCV patients were enrolled with a median follow-up of 129 weeks. They were mostly men (68%) and whites (73%) with median age of 43 years, diverse risk factors (33% injection drugs, 20% health care-associated, 3% sexual, and 45% unknown), and wide variations in peak alanine aminotransferase (143 to 3435 U/L) and total bilirubin levels (0.4 to 19.3 mg/dL). Viremia resolved spontaneously in 23% and persisted without therapy in 27%, whereas 50% received interferon α-based therapy with 90% cure (18/20). Distinct clinical scenarios included: (1) wide viremic fluctuations >1 log (65%) and intermittent HCV-RNA negativity; (2) autoantibodies (25% antinuclear antibodies, 69% antismooth muscle antibodies) or autoimmune features; (3) delayed spontaneous viral clearance in 2 patients; (4) rapid cirrhosis progression in 2 patients. AHCV is a heterogenous disease that requires careful monitoring. The lack of apparent risk factor in high proportion of patients and its diverse presentations warrant diagnostic vigilance.

Hepatitis C virus and the immunological response to hepatitis B virus vaccine in dialysis patients: meta-analysis of clinical studies.

PubMed

Fabrizi, F; Dixit, V; Martin, P; Messa, P

2011-12-01

It is well known that the seroconversion rate of patients following hepatitis B virus (HBV) vaccination is lower in uraemic than healthy subjects. A variety of inherited or acquired factors have been implicated in this diminished response, and the high prevalence of hepatitis C virus (HCV) infection among patients on maintenance dialysis has been suggested to play a role. However, the impact of HCV on the immune response to HB vaccine in patients receiving long-term dialysis is not entirely understood. Here, we evaluate the influence of HCV infection on the immunological response to HBV vaccine in dialysis population by performing a systematic review of the literature with a meta-analysis of clinical studies.We used the random-effects model of DerSimonian and Laird with heterogeneity and sensitivity analyses. The end-point of interest was the rate of patients showing seroprotective anti-hepatitis B titres at completion of HBV vaccine schedule among HCV-positive versus HCV-negative patients on chronic dialysis. We identified eight studies involving 520 unique patients on long-term dialysis. Aggregation of study results did not show a significant decrease in response rates among HCV-infected versus noninfected patients [pooled odds ratio = 0.621 (95% CI, 0.285; 1.353)]. The P-value was 0.007 for our test of study heterogeneity. Stratified analysis in various subgroups of interest did not meaningfully change our results. Our meta-analysis showed no association between immunological response to hepatitis B vaccine and HCV infection in individuals on long-term dialysis. These results support the use of recombinant vaccine against hepatitis B in patients on regular dialysis with HCV infection. © 2011 Blackwell Publishing Ltd.

The important role of early diagnosis and preventive management during a large-scale outbreak of hepatitis A in Thailand

PubMed Central

Poovorawan, Kittiyod; Chattakul, Paiboon; Chattakul, Sirirat; Thongmee, Thanunrat; Theamboonlers, Apiradee; Komolmit, Piyawat; Poovorawan, Yong

2013-01-01

Introduction Acute hepatitis A is a worldwide public health problem especially in developing countries. Recently, a large, community-wide outbreak of hepatitis A occurred in the northeast part of Thailand. Methods Demographic and clinical data as well as blood samples were collected and analyzed from patients with acute hepatitis who attended the Buengkan Provincial Hospital from June to September 2012. About 1619 patients with clinical symptoms of hepatitis A visited the hospital during the outbreak which manifested in three waves. Blood samples were collected from 205 patients. Results One hundred and seventy eight patients had hepatitis A confirmed by the presence of anti-hepatitis A virus (HAV) IgM and/or HAV-RNA. The sensitivities for anti-HAV IgM and HAV-RNA were 95.5% (170/178) and 61.8% (110/178), respectively. When HAV-RNA was combined with anti-HAV IgM test, this increased the diagnostic yield by 7.2% (8/111) in the early phase of the acute infection (less than 5 days). Investigation of the molecular structure of the detected viruses indicated that all of the infections were caused by HAV genotype IA. There were no fatalities from this outbreak. Rapid detection, health education, sanitation campaigns, and vaccination offered on a voluntary basis have steadily reduced the number of infected patients and stopped the outbreak. Conclusion Occasionally a large-scale outbreak of HAV genotype IA can occur. A combination of HAV-RNA and anti-HAV IgM tests can increase the diagnostic yield during the early phase of the acute infection. Early diagnosis and preventive management campaigns can slow down and stop the outbreak. PMID:24392680

CD4+ T-cell recovery with suppressive ART-induced rapid sequence evolution in hepatitis C virus envelope but not NS3.

PubMed

Liu, Lin; Nardo, David; Li, Eric; Wang, Gary P

2016-03-13

CD4 T-cell depletion from HIV infection leads to a global decline in anti-hepatitis C virus (HCV) envelope neutralizing antibody (nAb) response, which may play a role in accelerating liver fibrosis. An increase in anti-HCV nAb titers has been reported during antiretroviral therapy (ART) but its impact on HCV remains poorly understood. The objective of this study is to determine the effects of ART on long-term HCV evolution. We examined HCV quasispecies structure and long-term evolution in HIV/HCV coinfected patients with ART-induced CD4 T-cell recovery, and compared with patients with CD4 T-cell depletion from delayed ART. We applied a single-variant sequencing (SVS) method to construct authentic viral quasispecies and compared sequence evolution in HCV envelope, the primary target for humoral immune responses, and NS3, a target for cellular immunity, between the two cohorts. The SVS method corrected biases known to skew the proportions of viral variants, revealing authentic HCV quasispeices structures. We observed higher rates of HCV envelope sequence evolution in patients with ART-induced CD4 T-cell recovery, compared with patients with CD4 T-cell depletion from delayed ART (P = 0.03). Evolutionary rates for NS3 were considerably lower than the rates for envelope (P < 0.01), with no significant difference observed between the two groups. ART-induced CD4 T-cell recovery results in rapid sequence evolution in HCV envelope, but not in NS3. These results suggest that suppressive ART disproportionally enhances HCV-specific humoral responses more than cellular responses, resulting in rapid sequence evolution in HCV envelope but not NS3.

How to improve the quality of a disease management program for HIV-infected patients using a computerized data system. The Saint-Antoine Orchestra program.

PubMed

Fonquernie, F; Lacombe, K; Vincensini, J P; Boccara, F; Clozel, S; Ayouch Boda, A; Bollens, D; Campa, P; Pacanowski, J; Meynard, J L; Meyohas, M C; Girard, P M

2010-05-01

The emergence of non-AIDS-related events in the HIV-infected population experiencing a longer life expectancy implies the implementation of a comprehensive approach of HIV clinical management through better access to care, prevention, and early diagnosis of co-morbidities. The Orchestra program is a computer-assisted HIV care and support tool implemented since December 2004 in the outpatient clinic of a University Hospital set in Paris, France. The intervention aims at improving access to HIV information care and support specifically targeted five areas of actions: cardiovascular risk factors; gynecological follow-up; anti-hepatitis B virus (HBV) vaccine coverage; sexuality and prevention of sexually transmitted infections; and compliance to antiretrovirals. The impact of this program was examined prospectively on a "before-after" basis after a two-year implementation. In the two-year period, 1717 patients were regularly followed. The level of the database information significantly increased in time (low density lipoprotein (LDL) cholesterol and glycemia were informed in 74% of patients at inclusion versus 95% at two years, and 83% versus 97%, p < 0.001, respectively). The number of targeted interventions was also higher. For eligible women, papanicolaou smears and mammography were prescribed in 52% of cases after intervention, versus 44% at inclusion, p0.04 and 83% versus 50%, p < 0.001, respectively. Indicators of care eventually improved significantly. Initially 72% non-adherent patients declared to be adherent after the intervention ( p < 0.001) and 67% of patients with initial LDL-hypercholesterolemia normalized their LDL level within two years ( p < 0.001). The Orchestra program has provided a unique opportunity to assess and improve prevention and management of co-morbidities in HIV patients.

Essentials from the 2015 European AIDS Clinical Society (EACS) guidelines for the treatment of adult HIV-positive persons.

PubMed

Ryom, L; Boesecke, C; Gisler, V; Manzardo, C; Rockstroh, J K; Puoti, M; Furrer, H; Miro, J M; Gatell, J M; Pozniak, A; Behrens, G; Battegay, M; Lundgren, J D

2016-02-01

The European AIDS Clinical Society (EACS) guidelines are intended for all clinicians involved in the care of HIV-positive persons, and are available in print, online, and as a free App for download for iPhone and Android. The 2015 version of the EACS guidelines contains major revisions in all sections; antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Among the key revisions is the recommendation of ART for all HIV-positive persons, irrespectively of CD4 count, based on the Strategic Timing of AntiRetroviral Treatment (START) study results. The recommendations for the preferred and the alternative ART options have also been revised, and a new section on the use of pre-exposure prophylaxis (PrEP) has been added. A number of new antiretroviral drugs/drug combinations have been added to the updated tables on drug-drug interactions, adverse drug effects, dose adjustment for renal/liver insufficiency and for ART administration in persons with swallowing difficulties. The revisions of the coinfection section reflect the major advances in anti-hepatitis C virus (HCV) treatment with direct-acting antivirals with earlier start of treatment in individuals at increased risk of liver disease progression, and a phasing out of interferon-containing treatment regimens. The section on opportunistic diseases has been restructured according to individual pathogens/diseases and a new overview table has been added on CD4 count thresholds for different primary prophylaxes. The diagnosis and management of HIV infection and related coinfections, opportunistic diseases and comorbidities continue to require a multidisciplinary effort for which the 2015 version of the EACS guidelines provides an easily accessable and updated overview. © 2015 British HIV Association.

[Health information on the Internet and trust marks as quality indicators: vaccines case study].

PubMed

Mayer, Miguel Angel; Leis, Angela; Sanz, Ferran

2009-10-01

To find out the prevalence of quality trust marks present in websites and to analyse the quality of these websites displaying trust marks compared with those that do not display them, in order to put forward these trust marks as a quality indicator. Cross-sectional study. Internet. Websites on vaccines. Using "vacunas OR vaccines" as key words, the features of 40 web pages were analysed. These web pages were selected from the page results of two search engines, Google and Yahoo! Based on a total of 9 criteria, the average score of criteria fulfilled was 7 (95% CI 3.96-10.04) points for the web pages offered by Yahoo! and 7.3 (95% CI 3.86-10.74) offered by Google. Amongst web pages offered by Yahoo!, there were three with clearly inaccurate information, while there were four in the pages offered by Google. Trust marks were displayed in 20% and 30% medical web pages, respectively, and their presence reached statistical significance (P=0.033) when fulfilling the quality criteria compared with web pages where trust marks were not displayed. A wide variety of web pages was obtained by search engines and a large number of them with useless information. Although the websites analysed had a good quality, between 15% and 20% showed inaccurate information. Websites where trust marks were displayed had more quality than those that did not display one and none of them were included amongst those where inaccurate information was found.

Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II).

PubMed

Zeuzem, S; Flisiak, R; Vierling, J M; Mazur, W; Mazzella, G; Thongsawat, S; Abdurakhmanov, D; Van Kính, N; Calistru, P; Heo, J; Stanciu, C; Gould, M; Makara, M; Hsu, S-J; Buggisch, P; Samuel, D; Mutimer, D; Nault, B; Merz, M; Bao, W; Griffel, L H; Brass, C; Naoumov, N V

2015-10-01

Alisporivir (ALV) is an oral, host-targeting agent with pangenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance. To evaluate efficacy and safety of ALV plus peginterferon-α2a and ribavirin (PR) in treatment-naïve patients with chronic HCV genotype 1 infection. Double-blind, randomised, placebo-controlled, Phase 3 study evaluating ALV 600 mg once daily [response-guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received ≥12 weeks and 20% had received ≥24 weeks of ALV/PR triple therapy. A total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose-dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension. Alisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment-naïve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon-free combination regimens. © 2015 John Wiley & Sons Ltd.

Inhibitory effects of quercetin on the progression of liver fibrosis through the regulation of NF-кB/IкBα, p38 MAPK, and Bcl-2/Bax signaling.

PubMed

Wang, Rong; Zhang, Hai; Wang, Yuanyuan; Song, Fuxing; Yuan, Yongfang

2017-06-01

Quercetin, a natural flavonoid, has been used as a nutritional supplement for its anti-inflammatory and antioxidative properties. Quercetin was reported to exhibit a wide range of pharmacological properties, including its effect on anti-hepatic fibrosis. However, the anti-fibrotic mechanisms of quercetin have not been well-characterized to date. This study aimed to investigate the protective effects of quercetin on carbon tetrachloride (CCl 4 )-induced liver fibrosis in rats and to clarify its anti-hepatofibrotic mechanisms. We demonstrated that quercetin exhibited in-vivo hepatoprotective and anti-fibrogenic effects against CCl 4 -induced liver injury by improving the pathological manifestations, thereby reducing the activities of serum total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and decreasing the serum levels of hyaluronic acid (HA), laminin (LN), type IV collagen (IV-C) and procollagen III peptide (PIIIP). Furthermore, treatment with quercetin 5-15mg/kg inhibited the activation of NF-κB in a dose-dependent manner via inhibition of IкBα degradation and decreased the expression of p38 MAPK by inhibiting its phosphorylation. Additionally, in a dose-dependent manner, quercetin down-regulated Bax, up-regulated Bcl-2, and subsequently inhibited caspase-3 activation. Moreover, quercetin regulated inflammation factors and hepatic stellate cells (HSCs)-activation markers, such as TNF-α, IL-6, IL-1β, Cox-2, TGF-β, α-SMA, Colla1, Colla2, TIMP-1, MMP-1, and desmin. Taken together, quercetin prevented the progression of liver fibrosis in SD rats. The anti-fibrotic mechanisms of quercetin might be associated with its ability to regulate NF-кB/IкBα, p38 MAPK anti-inflammation signaling pathways to inhibit inflammation, and regulate Bcl-2/Bax anti-apoptosis signaling pathway to prevent liver cell apoptosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Genetic Diversity of the Hepatitis B Virus Strains in Cuba: Absence of West-African Genotypes despite the Transatlantic Slave Trade

PubMed Central

Rodríguez Lay, Licel A.; Corredor, Marité B.; Villalba, Maria C.; Frómeta, Susel S.; Wong, Meilin S.; Valdes, Lidunka; Samada, Marcia; Sausy, Aurélie; Hübschen, Judith M.; Muller, Claude P.

2015-01-01

Cuba is an HBsAg low-prevalence country with a high coverage of anti-hepatitis B vaccine. Its population is essentially the result of the population mix of Spanish descendants and former African slaves. Information about genetic characteristics of hepatitis B virus (HBV) strains circulating in the country is scarce. The HBV genotypes/subgenotypes, serotypes, mixed infections, and S gene mutations of 172 Cuban HBsAg and HBV-DNA positive patients were determined by direct sequencing and phylogenetic analysis. Phylogenetic analysis of HBV S gene sequences showed a predominance of genotype A (92.4%), subgenotype A2 (84.9%) and A1 (7.6%). Genotype D (7.0%) and subgenotype C1 (0.6%) were also detected but typical (sub)genotypes of contemporary West-Africa (E, A3) were conspicuously absent. All genotype A, D, and C strains exhibited sequence characteristics of the adw2, ayw2, and adrq serotypes, respectively. Thirty-three (19.1%) patients showed single, double, or multiple point mutations inside the Major Hydrophilic domain associated with vaccine escape; eighteen (10.5%) patients had mutations in the T-cell epitope (amino acids 28-51), and there were another 111 point mutations downstream of the S gene. One patient had an HBV A1/A2 mixed infection. This first genetic study of Cuban HBV viruses revealed only strains that were interspersed with strains from particularly Europe, America, and Asia. The absence of genotype E supports previous hypotheses about an only recent introduction of this genotype into the general population in Africa. The presence of well-known vaccine escape (3.5%) and viral resistance mutants (2.9%) warrants strain surveillance to guide vaccination and treatment strategies. PMID:25978398

Association of human leukocyte antigen polymorphism with outcomes of hepatitis B virus infection.

PubMed

Ramezani, Amitis; Hasanjani Roshan, Mohammad Reza; Kalantar, Ebrahim; Eslamifar, Ali; Banifazl, Mohammad; Taeb, Jaleh; Aghakhani, Arezoo; Gachkar, Latif; Velayati, Ali Akbar

2008-11-01

Host genetic and environmental factors are viewed as a common basis of the different outcomes of hepatitis B virus (HBV) infection. Human leukocyte antigen (HLA) plays an important role in immunological reaction to HBV infection. In this study, we aimed to determine the association between HBV infection and HLA-A, B, and DRB1 alleles in northern Iran. HLA-A, B, and DRB1 alleles in 33 patients with chronic hepatitis B (CHB) and 31 healthy carriers as the persistent group, and 30 subjects who had spontaneously recovered from HBV infection were analyzed by using the polymerase chain reaction (PCR)-sequence-specific primer (PCR-SSP) technique. The frequency of the HLA-A*33 allele was higher in the persistent group than in the recovered group (10.16% vs 0%, P < 0.008); the frequency of the DRB1*13 allele was lower in the persistent group than in the recovered group (3.13% vs 11.67%, P < 0.03). The frequency of the B*52 allele was higher in CHB patients than healthy carriers (7.58% vs 0%, P < 0.05). The logistic regression model showed that the presence of the HLA-DRB1*13 allele was the significant factor associated with protection against the persistency of HBV. There were significant differences between the HBV recovered group, CHB patients, and healthy carriers regarding age, hepatitis B e antigen, and anti-hepatitis B e positivity. HLA-A*33 was closely related with susceptibility to persisting hepatitis B infection, and HLA-DRB1*13 was closely related with protection against persisting hepatitis B in an Iranian population. These findings emphasized that the host HLA polymorphism is an important factor in determining the outcome of HBV infection.

A new subtype (subgenotype) Ac (A3) of hepatitis B virus and recombination between genotypes A and E in Cameroon.

PubMed

Kurbanov, Fuat; Tanaka, Yasuhito; Fujiwara, Kei; Sugauchi, Fuminaka; Mbanya, Dora; Zekeng, Leopold; Ndembi, Nicaise; Ngansop, Charlotte; Kaptue, Lazare; Miura, Tomoyuki; Ido, Eiji; Hayami, Masanori; Ichimura, Hiroshi; Mizokami, Masashi

2005-07-01

Blood samples (n=544) from two different populations (Pygmies and Bantus) in Cameroon, West Africa, were analysed. Serological tests indicated that the anti-hepatitis C virus (HCV) prevalence in Bantus (20.3 %) was higher than that in Pygmies (2.3 %, P<0.0001), whereas the distribution of hepatitis B virus (HBV) serological markers was equally high in both populations: in total, 9.4, 17.3 and 86.8 % for HBsAg, anti-HBs and anti-HBc, respectively. HBV genotype A (HBV/A) and HBV/E were predominant (43.5 % each) in both populations, and HBV/D was found in a minority (13 %). The preS/S region was sequenced in nine cases (five HBV/A and four HBV/E) and the complete genome in six cases (four HBV/A and two HBV/E). Subsequent phylogenetic analysis revealed that the HBV/A strains were distinct from the subtypes (subgenotypes) described previously, Ae (A2) and Aa (A1), and in the preS/S region they clustered with previously reported sequences from Cameroon. Based on the nucleotide difference from Aa (A1) and Ae (A2), more than 4 % in the complete genome, the Cameroonian strains were suggested to represent a new subtype (subgenotype), designated HBV/Ac (A3). A high (3.9 %) nucleotide divergence in HBV/Ac (A3) strains suggested that the subtype (subgenotype) has a long natural history in the population of Cameroon. One of the HBV/Ac (A3) strains was found to be a recombinant with an HBV/E-specific sequence in the polymerase reverse transcriptase domain. Further cohort studies will be required to assess detailed epidemiological, virological and clinical characteristics of HBV/Ac (A3), as well as its recombinant form.

Prevalence, risk factors, and impact of isolated antibody to hepatitis B core antigen and occult hepatitis B virus infection in HIV-1-infected pregnant women.

PubMed

Khamduang, Woottichai; Ngo-Giang-Huong, Nicole; Gaudy-Graffin, Catherine; Jourdain, Gonzague; Suwankornsakul, Weerapong; Jarupanich, Tapnarong; Chalermpolprapa, Veeradate; Nanta, Sirisak; Puarattana-Aroonkorn, Noossara; Tonmat, Sakchai; Lallemant, Marc; Goudeau, Alain; Sirirungsi, Wasna

2013-06-01

Prevalence and risk factors for isolated antibody to hepatitis B core antigen (anti-HBc) and occult hepatitis B virus (HBV) infection are not well known in human immunodeficiency virus type 1 (HIV-1)-infected pregnant women. It is unclear if women with occult infections are at risk of transmitting HBV to their infants. HIV-1-infected and HBV surface antigen (HBsAg)-negative pregnant women were tested for antibody to HBsAg (anti-HBs) and anti-HBc using enzyme immunoassay. Women with isolated anti-HBc were assessed for occult HBV infection, defined as HBV DNA levels >15 IU/mL, using the Abbott RealTime HBV DNA assay. Infants born to women with isolated anti-HBc and detectable HBV DNA were tested at 4 months of age for HBV DNA. Logistic regression analysis was used to identify factors associated with isolated anti-HBc and occult HBV infection. Among 1812 HIV-infected pregnant women, 1682 were HBsAg negative. Fourteen percent (95% confidence interval [CI], 12%-15%) of HBsAg-negative women had an isolated anti-HBc that was independently associated with low CD4 count, age >35 years, birth in northern Thailand, and positive anti-hepatitis C virus serology. Occult HBV infection was identified in 24% (95% CI, 18%-30%) of women with isolated anti-HBc, representing 2.6% (95% CI, 1.9%-3.5%) of HIV-1-infected pregnant women, and was inversely associated with HIV RNA levels. None of the women with isolated anti-HBc and occult HBV infection transmitted HBV to their infants. HIV-1-infected pregnant women with isolated anti-HBc and occult HBV infection have very low HBV DNA levels and are thus at very low risk to transmit HBV to their infants.

A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients.

PubMed

Davis, Gary L; Nelson, David R; Terrault, Norah; Pruett, Timothy L; Schiano, Thomas D; Fletcher, Courtney V; Sapan, Christine V; Riser, Laura N; Li, Yufeng; Whitley, Richard J; Gnann, John W

2005-08-01

Chronic hepatitis C is the most common indication for liver transplantation, but viral recurrence is universal and progressive graft injury occurs in most recipients. Our aim was to assess the safety, pharmacokinetics (PK), and antiviral effects of high doses of a human hepatitis C antibody enriched immune globulin product (HCIG) in patients undergoing liver transplantation for chronic hepatitis C. This was a multicenter, randomized, open-label, controlled trial conducted at 4 transplant centers in the United States. A total of 18 patients with chronic hepatitis C, who underwent liver transplantation, were randomized to receive low-dose HCIG (75 mg/kg) or high-dose HCIG (200 mg/kg), or no treatment. A total of 17 infusions of HCIG were administered in each treated patient over 14 weeks using a time-dependent dosing strategy based on the PK of anti-hepatitis B immune globulin in liver transplant recipients. Hepatitis C virus levels, liver enzymes, and liver biopsies were obtained serially throughout the study period. PK profiles of HCV antibodies were determined on days 4, 10, and 98. HCIG infusions were safe and tolerated. The infusion rate could not be maximized because of symptoms for 18% to 30% of the doses. The half-life of HCIG was extremely short immediately after transplantation but was gradually prolonged. In the high-dose group, serum alanine aminotransferase (ALT) levels normalized in most subjects and no patient developed hepatic fibrosis. However, serum HCV RNA levels were not suppressed at either dose. In conclusion, HCIG, an anti-HCV enriched immune globulin product, appears to be safe in patients with chronic hepatitis C undergoing liver transplantation. Further studies are required to determine whether the drug has beneficial effects in this group of patients.

Decrease in seroprevalence of Hepatitis A after the implementation of nationwide disposable tableware use in Taiwan

PubMed Central

2010-01-01

Background Taiwan is an endemic area of viral hepatitis, including hepatitis A, which is transmitted mainly from the fecal-oral route. In order to reduce the transmission through food intake, the government implemented a policy of nationwide disposal tableware use in public eating places in 1982. We conducted a study to estimate the seroprevalence of Hepatitis A in a group of workers in Taiwan in 2005, determine the risk factors, and compare seroprevalence to published estimates in Taiwan to evaluate changes in the seroprevalence after the implementation of the nationwide disposal tableware use. Methods We recruited workers of an industrial park during their annual health examinations in 2005 and measured their anti-hepatitis A virus IgG titer using microparticle enzyme immunoassay. We compared the seroprevalence across different birth cohorts within the study population and also analyzed data from previous studies. Results The overall sero-positive rate was 22.0% in the 11,777 participants. The rate was much lower among those who were covered by the program since birth (born after 1982) in comparison with those who were not (2.7% vs. 25.3%, p < 0.001). From the analyses of data from pervious studies, we found the age-specific rates were similar in cohorts born in or after 1982 across studies conducted in different time periods but decreased with the calendar year in cohorts born before 1982. In particular, the age-specific seroprevalence dropped to less than one third in a three-year period among those who were born around 1982. Conclusions Data from both the current and previous studies in different time periods supported the effectiveness of disposal tableware in preventing the transmission of hepatitis A. PMID:21092247

[Construction of a plant effective expression vector containing the gene of hepatitis B virus surface antigen].

PubMed

Lin, Bing-Ying; Jin, Zhi-Qiang; Li, Mei

2006-11-01

To construct a plant effective expression vector driven by a fruit specific promoter for the expression of hepatitis B virus surface antigen (HBsAg), to further improve the expression of exogenous gene in plant, and to prepare for the development of an effective anti-hepatitis vaccine. Tomato fruit-specific promoters' gene 2A12 and E8 were respectively introduced to pBPFOmega7 to form pB2A12 and pBE8. The DNA fragment containing HBsAg-s gene from plasmid YEP-HBs was inserted respectively into pB2A12 and pBE8 to form pB2A12-HBs and pBE8-HBs. The fragment containing "p35S+2A12+Omega+HBsAg-s+Tnos" of the pB2A12-HBs was sub-cloned into plasmid pCAMBIA1301 to yield the reconstructed plant binary expression plasmid pCAM2A12-HBs, and the fragment containing "p35S+E8+Omega+HBsAg-s+Tnos" of the pBE8-HBs was sub-cloned into plasmid pCAMBIA1301 to yield the plasmid pCAME8-HBs. The inserted gene HBsAg and fruit-specific promoters in the reconstructed plant binary expression vectors were confirmed by sequencing. Then, pCAM2A12-HBs and pCAME8-HBs were directly introduced into Agrobacterium tumefaciens strain EHA105. Digestion with restriction enzymes proved that all recombinant vectors had the inserts with expected length of the target fragments, and the sequencing results were confirmed correct. In this study, plant expression vector containing HBsAg gene driven by fruit specific promoter and CaMV35s promoter was successfully constructed.

Update on occult hepatitis B virus infection

PubMed Central

Makvandi, Manoochehr

2016-01-01

The event of mutations in the surface antigen gene of hepatitis B virus (HBV) results in undetectable hepatitis B surface antigen with positive/negative anti-hepatitis B core (anti-HBc) antibody status in serum and this phenomenon is named occult hepatitis B infection (OBI). The presence of anti-HBc antibody in serum is an important key for OBI tracking, although about 20% of OBI cases are negative for anti-HBc antibody. The diagnosis of OBI is mainly based on polymerase chain reaction (PCR) and real-time PCR assays. However, real-time PCR is a more reliable method than PCR. OBI is a great issue for the public health problem and a challenge for the clinical entity worldwide. The persistence of OBI may lead to the development of cirrhosis and hepatocellular carcinoma. With regard to OBI complications, the screening of HBV DNA by the highly sensitive molecular means should be implemented for: (1) patients with a previous history of chronic or acute HBV infection; (2) patients co-infected with hepatitis C virus/human immunodeficiency virus; (3) patients undergoing chemotherapy or anti-CD20 therapy; (4) recipients of organ transplant; (5) blood donors; (6) organ transplant donors; (7) thalassemia and hemophilia patients; (8) health care workers; (9) patients with liver related disease (cryptogenic); (10) hemodialysis patients; (11) patients undergoing lamivudine or interferon therapy; and (12) children in time of HBV vaccination especially in highly endemic areas of HBV. Active HBV vaccination should be implemented for the close relatives of patients who are negative for OBI markers. Thus, the goal of this review is to evaluate the rate of OBI with a focus on status of high risk groups in different regions of the world. PMID:27818588

High Prevalence and Diversity of Hepatitis Viruses in Suspected Cases of Yellow Fever in the Democratic Republic of Congo

PubMed Central

Le Gal, Frédéric; Ngwaka-Matsung, Nadine; Ahuka-Mundeke, Steve; Onanga, Richard; Pukuta-Simbu, Elisabeth; Gerber, Athenaïs; Abbate, Jessica L.; Mwamba, Dieudonné; Berthet, Nicolas; Leroy, Eric Maurice; Muyembe-Tamfum, Jean-Jacques

2017-01-01

ABSTRACT The majority of patients with acute febrile jaundice (>95%) identified through a yellow fever surveillance program in the Democratic Republic of Congo (DRC) test negative for antibodies against yellow fever virus. However, no etiological investigation has ever been carried out on these patients. Here, we tested for hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV), hepatitis D (HDV), and hepatitis E (HEV) viruses, all of which can cause acute febrile jaundice, in patients included in the yellow fever surveillance program in the DRC. On a total of 498 serum samples collected from suspected cases of yellow fever from January 2003 to January 2012, enzyme-linked immunosorbent assay (ELISA) techniques were used to screen for antibodies against HAV (IgM) and HEV (IgM) and for antigens and antibodies against HBV (HBsAg and anti-hepatitis B core protein [HBc] IgM, respectively), HCV, and HDV. Viral loads and genotypes were determined for HBV and HVD. Viral hepatitis serological markers were diagnosed in 218 (43.7%) patients. The seroprevalences were 16.7% for HAV, 24.6% for HBV, 2.3% for HCV, and 10.4% for HEV, and 26.1% of HBV-positive patients were also infected with HDV. Median viral loads were 4.19 × 105 IU/ml for HBV (range, 769 to 9.82 × 109 IU/ml) and 1.4 × 106 IU/ml for HDV (range, 3.1 × 102 to 2.9 × 108 IU/ml). Genotypes A, E, and D of HBV and genotype 1 of HDV were detected. These high hepatitis prevalence rates highlight the necessity to include screening for hepatitis viruses in the yellow fever surveillance program in the DRC. PMID:28202798

High Prevalence and Diversity of Hepatitis Viruses in Suspected Cases of Yellow Fever in the Democratic Republic of Congo.

PubMed

Makiala-Mandanda, Sheila; Le Gal, Frédéric; Ngwaka-Matsung, Nadine; Ahuka-Mundeke, Steve; Onanga, Richard; Bivigou-Mboumba, Berthold; Pukuta-Simbu, Elisabeth; Gerber, Athenaïs; Abbate, Jessica L; Mwamba, Dieudonné; Berthet, Nicolas; Leroy, Eric Maurice; Muyembe-Tamfum, Jean-Jacques; Becquart, Pierre

2017-05-01

The majority of patients with acute febrile jaundice (>95%) identified through a yellow fever surveillance program in the Democratic Republic of Congo (DRC) test negative for antibodies against yellow fever virus. However, no etiological investigation has ever been carried out on these patients. Here, we tested for hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV), hepatitis D (HDV), and hepatitis E (HEV) viruses, all of which can cause acute febrile jaundice, in patients included in the yellow fever surveillance program in the DRC. On a total of 498 serum samples collected from suspected cases of yellow fever from January 2003 to January 2012, enzyme-linked immunosorbent assay (ELISA) techniques were used to screen for antibodies against HAV (IgM) and HEV (IgM) and for antigens and antibodies against HBV (HBsAg and anti-hepatitis B core protein [HBc] IgM, respectively), HCV, and HDV. Viral loads and genotypes were determined for HBV and HVD. Viral hepatitis serological markers were diagnosed in 218 (43.7%) patients. The seroprevalences were 16.7% for HAV, 24.6% for HBV, 2.3% for HCV, and 10.4% for HEV, and 26.1% of HBV-positive patients were also infected with HDV. Median viral loads were 4.19 × 10 5 IU/ml for HBV (range, 769 to 9.82 × 10 9 IU/ml) and 1.4 × 10 6 IU/ml for HDV (range, 3.1 × 10 2 to 2.9 × 10 8 IU/ml). Genotypes A, E, and D of HBV and genotype 1 of HDV were detected. These high hepatitis prevalence rates highlight the necessity to include screening for hepatitis viruses in the yellow fever surveillance program in the DRC. Copyright © 2017 Makiala-Mandanda et al.

Induction of a dwarf phenotype with IBH1 may enable increased production of plant-made pharmaceuticals in plant factory conditions.

PubMed

Nagatoshi, Yukari; Ikeda, Miho; Kishi, Hiroyuki; Hiratsu, Keiichiro; Muraguchi, Atsushi; Ohme-Takagi, Masaru

2016-03-01

Year-round production in a contained, environmentally controlled 'plant factory' may provide a cost-effective method to produce pharmaceuticals and other high-value products. However, cost-effective production may require substantial modification of the host plant phenotype; for example, using dwarf plants can enable the growth of more plants in a given volume by allowing more plants per shelf and enabling more shelves to be stacked vertically. We show here that the expression of the chimeric repressor for Arabidopsis AtIBH1 (P35S:AtIBH1SRDX) in transgenic tobacco plants (Nicotiana tabacum) induces a dwarf phenotype, with reduced cell size. We estimate that, in a given volume of cultivation space, we can grow five times more AtIBH1SRDX plants than wild-type plants. Although, the AtIBH1SRDX plants also showed reduced biomass compared with wild-type plants, they produced about four times more biomass per unit of cultivation volume. To test whether the dwarf phenotype affects the production of recombinant proteins, we expressed the genes for anti-hepatitis B virus antibodies (anti-HBs) in tobacco plants and found that the production of anti-HBs per unit fresh weight did not significantly differ between wild-type and AtIBH1SRDX plants. These data indicate that P35S:AtIBH1SRDX plants produced about fourfold more antibody per unit of cultivation volume, compared with wild type. Our results indicate that AtIBH1SRDX provides a useful tool for the modification of plant phenotype for cost-effective production of high-value products by stably transformed plants in plant factory conditions. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Modeling the long-term persistence of hepatitis A antibody after a two-dose vaccination schedule in Argentinean children.

PubMed

López, Eduardo L; Contrini, María Marta; Mistchenko, Alicia; Kieffer, Alexia; Baggaley, Rebecca F; Di Tanna, Gian Luca; Desai, Kamal; Rasuli, Anvar; Armoni, Judith

2015-04-01

Long-term seroprotection data are essential for decision-making on the need and timing of vaccine boosters. Based on data from longitudinal serological studies, modeling can provide estimates on long-term antibody persistence and inform such decision-making. We examined long-term anti-hepatitis A virus (anti-HAV) antibody persistence in Argentinean children ≤15 years after the initial study where they completed a 2-dose course of inactivated hepatitis A vaccine (Avaxim 80U Pediatric, Sanofi Pasteur, Lyon, France). Blood serum samples were taken at baseline, 2 weeks (post first dose), 6 months (pre-booster), 6.5 months (post-booster), 10 years and 14-15 years after first vaccine dose. We fitted 8 statistical model types, predominantly mixed effects models, to anti-HAV persistence data, to identify the most appropriate and best fitting models for our data set and to predict individuals' anti-HAV levels and seroprotection rates up to 30 years post vaccination. Fifty-four children (mean age at enrollment 30.4 months) were enrolled up to 15 years post first vaccine dose. There were 3 distinct periods of antibody concentration: rapid rise up to peak concentration post-booster, rapid decay from post-booster to 10 years, followed by slower decay. A 3-segmented linear mixed effects model was the most appropriate for the data set. Extrapolating based on the available 14-15-year follow-up, the analysis predicted that 88% of individuals anti-HAV seronegative prior to vaccination would remain seroprotected at 30 years post vaccination and lifelong seroprotection for vaccinees seropositive prior to vaccination. Currently available data demonstrate that Avaxim 80U Pediatric confers to most vaccinees a high level of seroprotection against hepatitis A infection for at least 20-30 years.

Association of the Interleukin-27 Gene Expression and Hepatitis B Virus Infection in Liver Transplanted Patients.

PubMed

Zare, Abdolhossein; Karimi, Mohammad Hossein; Rashki, Ahmad; Geramizadeh, Bita; Afshari, Afsoon; Miri, Hamid Reza; Yaghobi, Ramin

2017-10-01

Hepatitis B viral infection is among the most common causes of cirrhosis and hepatocellular carcinoma and a frequent viral indication for liver transplant. Cytokine-mediated immunity plays a critical role in introducing and promoting hepatitis B virus outcomes and in graft microenvironment. Interleukin 27 is a heterodimeric cytokine and a member of interleukin-6/interleukin-12 family. Interleukin-27 shows a broad range of pro- and antiinflammatory properties and plays a determining role during immune responses in combating hepatitis B virus. Therefore, in this study, the possible association between expressions of interleukin-27 gene with hepatitis B virus infection was evaluated in liver transplant patients. In a cross-sectional study from liver transplant patients with the risk of hepatitis B virus infection who admitted to Namazi Hospital affiliated to Shiraz University of Medical Sciences, 50 patients were selected and subgrouped to 25 hepatitis B virus-infected and 25 noninfected ones between years 2011 and 2013. The 25 healthy controls also were enrolled in this study. The presence of hepatitis B virus infection was assessed using polymerase chain reaction and enzyme-linked immunosorbent assay protocols in liver transplant patients. In addition, the interleukin-27 gene expression level was analyzed using an in-house-SYBER Green real time polymerase chain reaction method. The rate of interleukin-27 gene expression level was statistically analyzed in studied patient groups and controls using the Livak (2-▵▵CT) method. The expression level of interleukin-27 gene was increased 10.27- and 2.36-fold in hepatitis B virus-infected and uninfected liver transplanted patients compared with healthy controls. Hepatitis B virus infection can lead to overexpression of interleukin-27 gene in liver transplant patients compared with uninfected ones and controls. However, further studies are needed to characterize the effective antihepatitis B virus effects of interleukin

In vitro evaluation of novel antiviral activities of 60 medicinal plants extracts against hepatitis B virus.

PubMed

Arbab, Ahmed Hassan; Parvez, Mohammad Khalid; Al-Dosari, Mohammed Salem; Al-Rehaily, Adnan Jathlan

2017-07-01

Currently, >35 Saudi Arabian medicinal plants are traditionally used for various liver disorders without a scientific rationale. This is the first experimental evaluation of the anti-hepatitis B virus (HBV) potential of the total ethanolic and sequential organic extracts of 60 candidate medicinal plants. The extracts were tested for toxicity on HepG2.2.15 cells and cytotoxicity concentration (CC 50 ) values were determined. The extracts were further investigated on HepG2.2.15 cells for anti-HBV activities by analyzing the inhibition of HBsAg and HBeAg production in the culture supernatants, and their half maximal inhibitory concentration (IC 50 ) and therapeutic index (TI) values were determined. Of the screened plants, Guiera senegalensis (dichloromethane extract, IC 50 =10.65), Pulicaria crispa (ethyl acetate extract, IC 50 =14.45), Coccinea grandis (total ethanol extract, IC 50 =31.57), Fumaria parviflora (hexane extract, IC 50 =35.44), Capparis decidua (aqueous extract, IC 50 =66.82), Corallocarpus epigeus (total ethanol extract, IC 50 =71.9), Indigofera caerulea (methanol extract, IC 50 =73.21), Abutilon figarianum (dichloromethane extract, IC 50 =99.76) and Acacia oerfota (total ethanol extract, IC 50 =101.46) demonstrated novel anti-HBV activities in a time- and dose-dependent manner. Further qualitative phytochemical analysis of the active extracts revealed the presence of alkaloids, tannins, flavonoids and saponins, which are attributed to antiviral efficacies. In conclusion, P. crispa, G. senegalensis and F. parviflora had the most promising anti-HBV potentials, including those of C. decidua , C. epigeus, A. figarianum , A. oerfota and I. caerulea with marked activities. However, a detailed phytochemical study of these extracts is essential to isolate the active principle(s) responsible for their novel anti-HBV potential.

Semen Brassicae ameliorates hepatic fibrosis by regulating transforming growth factor-β1/Smad, nuclear factor-κB, and AKT signaling pathways in rats.

PubMed

Cao, Si; Zheng, Baoping; Chen, Tao; Chang, Xinfeng; Yin, Bao; Huang, Zhihua; Shuai, Ping; Han, Limin

2018-01-01

There is no effective treatment for liver fibrosis, which is a common phase during the progression of many chronic liver diseases to cirrhosis. Previous studies found that Semen Brassicae therapy can effectively improve the clinical symptoms of patients with asthma, allergic rhinitis, and chronic lung diseases; however, its effects on liver fibrosis in rats and its possible mechanisms of action remain unclear. Rats were injected intraperitoneally with 4% thioacetamide aqueous solution (5 mL·kg -1 ) at a dose of 200 mg·kg -1 twice a week for 8 consecutive weeks to establish the liver fibrosis model and were then treated with different concentrations of Semen Brassicae extract. After Semen Brassicae treatment, the morphology of the liver tissue was analyzed using hematoxylin and eosin and Masson's trichrome staining, and liver index and liver fibrosis grade were calculated. Thereafter, the levels of collagen-I, collagen-III, α-SMA, transforming growth factor (TGF)-β1, p-Smad 2/3, Smad 2/3, Smad4, NF-κB-p65, p-NF-κB-p65, IL-1β, IL-6, AKT, and p-AKT were determined using Western blotting. Compared with the untreated model group, the Semen Brassicae-treated group showed significantly decreased liver function indices; expression levels of collagen-I, collagen-III, and α-SMA; and hepatic fibrosis. Further studies also showed that the expression of TGF-β1, Smad4, p-Smad 2/3/Smad 2/3, p-NF-κB-p65/NF-κB-p65, IL-1β, IL-6, and p-AKT/AKT significantly decreased after the treatment. These results indicate that Semen Brassicae exhibits an anti-hepatic fibrosis effect, and the underlying mechanism of action may be related to the regulation of TGF-β1/Smad, NF-κB, and AKT signaling pathways and the reduction of extracellular matrix deposition.

Low accuracy of the national reporting system of acute hepatitis C infection in Taiwan, 1995-2004.

PubMed

Kee, Kwong-Ming; Hung, Chi-Ming; Wang, Jing-Houng; Hung, Chao-Hung; Chen, Pao-Fei; Lin, Kuo-Sin; Lu, Sheng-Nan

2010-07-01

This study attempted to clarify accuracy of acute hepatitis C (AHC) and its clinical characteristics. We reviewed 632 reported cases from national surveillance data of the Taiwan Center for Disease Control between 1995 and 2004, and reclassified diagnoses. A definite case was defined as alanine aminotransferase (ALT) > 10 x the upper limit of normal (ULN) with seroconversion of anti-hepatitis C virus antibody (anti-HCV). A probable case was defined as (i) seroconversion of anti-HCV and/or elevated ALT levels; or (ii) anti-HCV(+) but titers increased (from < 40 S/CO to >or= 40 S/CO) and ALT > 10 x the ULN. A suspected case was defined as initial anti-HCV(+) and ALT level > 10 x the ULN and/or jaundice. Excluded cases were defined as ALT levels less than 10 x ULN with initial positive anti-HCV Ab. A total of 310 (49%) cases were confirmed as AHC; these included 95 (15%) definite and 215 (34%) probable cases. Higher incidence rates and accuracy of AHC were demonstrated in the southern area significantly if compared with northern, eastern and central areas, respectively (all P < 0.05). On comparison between blood centers and hospitals, more AHC cases were found in Southern Taiwan than in other areas (157/73 vs 24/40, P < 0.001), younger mean age (33.3 +/- 11.1 vs 49.3 +/- 16.4, P < 0.001), lower ALT levels (263.1 +/- 200.9 vs 1264.2 +/- 706.8, P < 0.001) and male predominance (191/39 vs 46/18, P = 0.046). This study showed our reporting system over-estimated the AHC diagnosis, which is also a common issue worldwide. Greater efforts are needed to establish appropriate reporting systems, as well as more supplemental methods to distinguish between prevalent and incident cases.

Assessment of hepatitis B virus antibody titers in childhood cancer survivors.

PubMed

Fayea, Najwa Yahya; Kandil, Shaimaa Mohamed; Boujettif, Khadijah; Fouda, Ashraf Elsayed

2017-09-01

Pediatric patients suffering from cancer are at risk of hepatitis B virus (HBV) infection and its related complications even though it is considered a vaccine preventable disease. Little is known of the effects of chemotherapy, and even less is known regarding the impact of HBV booster on HBV antibody titers. It is the purpose of this study to investigate and measure the prevalence of the antihepatitis B surface antibodies (HBsAb) in childhood cancer survivors after completion of their chemotherapy treatment and to further evaluate survivors' response to a single booster dose of HBV vaccine. This observational, cross-sectional retrospective study included 43 patients, of which 37 (86%) were found to be seronegative (HBsAb titer <10 mIU/ml). The notable result was that, of the seronegative patients who received a booster dose of HBV vaccine, 90% of the tested cases exhibited a successful raising of HBsAb titers >10 mIU/ml. Childhood cancer survivors have high seronegative rates for HBV and the majority of the patients achieved HBsAb titer > 10mIU/ml with a single booster dose of HBV vaccine, which is worth further investigation and research. This study suggests revaccination against HBV post-chemotherapy treatment, as the recommended advice, especially in countries with a high prevalence of HBV infection. What is Known: • There is a variable prevalence of low HBsAb titers measured after the end of chemotherapy in childhood cancer survivors. • There are no universal guidelines for revaccination of these patients. What is New: • This research identified that 86% of childhood cancer survivors treated with standard chemotherapy were seronegative for HBV infection. • A single booster dose HBV vaccine was successful for the majority of patients (90%) to achieve HBsAb titers >10 mIU/ml.

Prevalence and presentation of hepatitis B and C virus (HBV and HCV) infection in Vietnamese Americans via serial community serologic testing.

PubMed

Nguyen, Kelvin; Van Nguyen, Thai; Shen, Duke; Xia, Victor; Tran, Diep; Banh, Khanh; Ruan, Victor; Hu, Ke-Qin

2015-02-01

The prevalence of hepatitis B virus (HBV) infection is reportedly high in Vietnamese Americans (VAs), but most previous studies did not assess full HBV serology, and not the prevalence of HBV and hepatitis C virus (HCV) infection simultaneously. The aim of the study is to assess the prevalence of different HBV serologies and HCV infection in VAs. This study was based on the data collected by testing for Hepatitis B surface antigen (HBsAg), anti-hepatitis B core antibody (HBcAb IgG), anti-HBs antibody (HBsAb), and anti-HCV antibody (anti-HCV) in a series of community screening in VAs in Orange County, California. In 1,405 VA participants, the mean age was 51 (17-87) years, 45.1% were males; 68.2%, married; 97.2%, born in Vietnam. Most of the participants were non-US born with their primary language being non-English and with limited access to health care. Of the 1,405 cases, 124 (8.8%) were confirmed HBV infection by HBsAg+; 81 (5.8%), HCV infection by anti-HCV+; including four (0.3%) with HBV/HCV coinfection. Twelve percent of the participants with confirmed HBV infection thought they were previously tested negative, while 29.7% of the participants with confirmed HCV infection thought they were previously tested negative. In this cohort, 15.4% were HBsAg-/HBsAb-/HBcAb IgG-, i.e. being susceptible to HBV infection. In HCV infected participants, 65.4% were born between 1945 and 1965. This large serial survey and screening in the Vietnamese American community confirmed the rates of HBV and HCV infection to be as high as 8.8% and 5.8%, respectively. We have also identified factors related to HBV and HCV infection in this high-risk population.

Development of models to predict early post-transplant recurrence of hepatocellular carcinoma that also integrate the quality and characteristics of the liver graft: A national registry study in China.

PubMed

Ling, Qi; Liu, Jimin; Zhuo, Jianyong; Zhuang, Runzhou; Huang, Haitao; He, Xiangxiang; Xu, Xiao; Zheng, Shusen

2018-04-27

Donor characteristics and graft quality were recently reported to play an important role in the recurrence of hepatocellular carcinoma after liver transplantation. Our aim was to establish a prognostic model by using both donor and recipient variables. Data of 1,010 adult patients (training/validation: 2/1) undergoing primary liver transplantation for hepatocellular carcinoma were extracted from the China Liver Transplant Registry database and analyzed retrospectively. A multivariate competing risk regression model was developed and used to generate a nomogram predicting the likelihood of post-transplant hepatocellular carcinoma recurrence. Of 673 patients in the training cohort, 70 (10.4%) had hepatocellular carcinoma recurrence with a median recurrence time of 6 months (interquartile range: 4-25 months). Cold ischemia time was the only independent donor prognostic factor for predicting hepatocellular carcinoma recurrence (hazard ratio = 2.234, P = .007). The optimal cutoff value was 12 hours when patients were grouped according to cold ischemia time at 2-hour intervals. Integrating cold ischemia time into the Milan criteria (liver transplantation candidate selection criteria) improved the accuracy for predicting hepatocellular carcinoma recurrence in both training and validation sets (P < .05). A nomogram composed of cold ischemia time, tumor burden, differentiation, and α-fetoprotein level proved to be accurate and reliable in predicting the likelihood of 1-year hepatocellular carcinoma recurrence after liver transplantation. Additionally, donor anti-hepatitis B core antibody positivity, prolonged cold ischemia time, and anhepatic time were linked to the intrahepatic recurrence, whereas older donor age, prolonged donor warm ischemia time, cold ischemia time, and ABO incompatibility were relevant to the extrahepatic recurrence. The graft quality integrated models exhibited considerable predictive accuracy in early hepatocellular carcinoma recurrence risk

Lasting immune memory against hepatitis B in 12-13-year-old adolescents previously vaccinated with 4 doses of hexavalent DTPa-HBV-IPV/Hib vaccine in infancy.

PubMed

Behre, Ulrich; Van Der Meeren, Olivier; Crasta, Priya; Hanssens, Linda; Mesaros, Narcisa

2016-11-01

Vaccinating infants against hepatitis B virus (HBV) is the most effective way of preventing the disease. However, since HBV exposure can increase during adolescence, it is essential that antibody persistence is maintained. We evaluated the antibody persistence and immune memory against hepatitis B, in 12-13 y olds who had received complete primary + booster vaccination with diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus/Haemophilus influenza type b (DTPa-HBV-IPV/Hib) vaccine in infancy. Open phase-IV study conducted at 12 centers in Germany [NCT02052661]. Adolescents aged 12-13 y, vaccinated with 4 doses of DTPa-HBV-IPV/Hib (Infanrix hexa™, GSK Vaccines) in infancy, received a single challenge dose of monovalent pediatric hepatitis B vaccine (Engerix™-B Kinder; GSK Vaccines). Blood samples were taken before and 1-month post-challenge to measure anti-hepatitis B (anti-HBs) antibodies using a chemiluminescence immunoassay (seroprotection cut-off: ≥10 mIU/ml). Post-challenge adverse events (AEs) were monitored. 300 subjects were vaccinated; of 293 subjects in the ATP immunogenicity cohort, 60.5% had pre-challenge anti-HBs antibodies ≥10 mIU/ml, which rose to 97.6% post-challenge (≥100 mIU/ml in 94.1%). An anamnestic response was seen in 96.5% subjects. A 150-fold increase in antibody geometric mean concentrations was observed (22.4 to 3502.6 mIU/ml). Pain (44%) and fatigue (24.3%) were the most frequent solicited local and general AEs, respectively; 14.7% subjects reported unsolicited symptoms during the 31-day post-vaccination period. Two vaccine-unrelated serious AEs occurred. Vaccination with DTPa-HBV-IPV/Hib in infancy induces sustained seroprotection and immune memory against HBV, as shown by the strong anamnestic response to the hepatitis B vaccine challenge in 12-13 year-old adolescents.

Hepatitis E virus: Western Cape, South Africa

PubMed Central

Madden, Richie G; Wallace, Sebastian; Sonderup, Mark; Korsman, Stephen; Chivese, Tawanda; Gavine, Bronwyn; Edem, Aniefiok; Govender, Roxy; English, Nathan; Kaiyamo, Christy; Lutchman, Odelia; van der Eijk, Annemiek A; Pas, Suzan D; Webb, Glynn W; Palmer, Joanne; Goddard, Elizabeth; Wasserman, Sean; Dalton, Harry R; Spearman, C Wendy

2016-01-01

AIM To conduct a prospective assessment of anti-hepatitis E virus (HEV) IgG seroprevalence in the Western Cape Province of South Africa in conjunction with evaluating risk factors for exposure. METHODS Consenting participants attending clinics and wards of Groote Schuur, Red Cross Children’s Hospital and their affiliated teaching hospitals in Cape Town, South Africa, were sampled. Healthy adults attending blood donor clinics were also recruited. Patients with known liver disease were excluded and all major ethnic/race groups were included to broadly represent local demographics. Relevant demographic data was captured at the time of sampling using an interviewer-administered confidential questionnaire. Human immunodeficiency virus (HIV) status was self-disclosed. HEV IgG testing was performed using the Wantai® assay. RESULTS HEV is endemic in the region with a seroprevalence of 27.9% (n = 324/1161) 95%CI: 25.3%-30.5% (21.9% when age-adjusted) with no significant differences between ethnic groups or HIV status. Seroprevalence in children is low but rapidly increases in early adulthood. With univariate analysis, age ≥ 30 years old, pork and bacon/ham consumption suggested risk. In the multivariate analysis, the highest risk factor for HEV IgG seropositivity (OR = 7.679, 95%CI: 5.38-10.96, P < 0.001) was being 30 years or older followed by pork consumption (OR = 2.052, 95%CI: 1.39-3.03, P < 0.001). A recent clinical case demonstrates that HEV genotype 3 may be currently circulating in the Western Cape. CONCLUSION Hepatitis E seroprevalence was considerably higher than previously thought suggesting that hepatitis E warrants consideration in any patient presenting with an unexplained hepatitis in the Western Cape, irrespective of travel history, age or ethnicity. PMID:27956810

Prevalence of antibodies against transfusion-transmissible infections (TTI) in blood donors from the Colombian eastern region.

PubMed

Gómez, Lina Andrea; Peñuela, Oscar; Higuera, Fernando

2014-01-01

The main purpose of this study was to establish the prevalence of antibodies against five transfusion-transmissible infections (TTIs) in blood donors from one of the most important blood banks in Colombia. A cross-sectional, descriptive and case control study was performed from a database of Higuera-Escalante blood bank, for a period of a year. Serum was used for donor screening. Surface antigens for hepatitis B (HbsAg), anti-hepatitis C antibodies, Chagas disease, syphilis, and HIV were identified. Chemiluminescent Microparticle Immunoassay (CMIA, Abbott Diagnostics) was performed. From 41,575 total donors analyzed, 1,226 were reactive for any of the infectious markers (total prevalence of 2.95%). The prevalence of specific infections was: Chagas disease 0.49%, HbsAg 0.21%, HCV 0.45%, HIV 0.12%, and syphilis 1.68%. Reactivity was more frequent in men (n = 785, 64%) with a mean age of 36.35 years. HIV was present in the youngest donors with a mean age of 26.5 years (IC 95%: 23.6 - 27.6); on the other hand, Chagas disease was found in the oldest donor population, with a mean age of 40 years (IC 95%: 39.1 - 41.3). Identifying the prevalence of circulating antibodies against transfusion transmissible infections allows us to establish an epidemiological profile of donors inhabiting the geographic catchment area of our blood bank. Total prevalence in this study was 2.95% for any of the five markers. Syphilis prevalence demonstrates its high distribution within the blood donor population of our country, although this result could be influenced by the high rate of false-reactive test. Chagas disease is endemic in Santander, Colombia, which correlates with the results obtained in this study.

Current state of and needs for hepatitis B screening: results of a large screening study in a low-prevalent, metropolitan region.

PubMed

Bottero, Julie; Boyd, Anders; Lemoine, Maud; Carrat, Fabrice; Gozlan, Joel; Collignon, Anne; Boo, Nicolas; Dhotte, Philippe; Varsat, Brigitte; Muller, Gerard; Cha, Olivier; Valin, Nadia; Nau, Jean; Campa, Pauline; Silbermann, Benjamin; Bary, Marc; Girard, Pierre-Marie; Lacombe, Karine

2014-01-01

In low hepatitis B virus (HBV)-prevalent countries, most HBV-infected persons are unaware of their status. We aimed to evaluate whether (i) previous HBV-testing, (ii) physicians decision to screen, and (iii) CDC's recommendations identified infected individuals and which risk-factor groups needing testing. During a mass, multi-center HBV-screening study from September 2010-August 2011, 3929 participants were screened for hepatitis B surface antigen (HBsAg), anti-HBs and anti-Hepatitis B core antibodies (anti-HBcAb). Questions on HBV risk-factors and testing practices were asked to participants, while participants' eligibility for HBV-testing was asked to study medical professionals. 85 (2.2%) participants were HBsAg-positive, while 659 (16.8%) had either resolved HBV infection or isolated anti-HBcAb. When comparing practices, HBV-testing was more likely to occur in HBV-infected participants if Centers for Disease Control and Prevention (CDC) recommendations were used (Sensitivity = 100%, 95%CI: 95.8-100) than physicians' discretion (Sensitivity = 87.1%, 95%CI: 78.0-93.4) or previous HBV-test (Sensitivity = 36.5%, 95%CI: 26.3-47.6) (p<0.0001). Nevertheless, many non-infected individuals would still have been screened using CDC-recommendations (Specificity = 31.1%, 95%CI: 29.6-32.6). Using multivariable logistic regression, HBsAg-positive status was significantly associated with the following: males, originating from high HBV-endemic region, contact with HBV-infected individual, without national healthcare, and intravenous-drug user (IDU). Of these risk-factors, physician's discretion for testing HBV was not significantly associated with participants' geographical origin or IDU. Missed opportunities of HBV-screening are largely due to underestimating country of origin as a risk-factor. Applying CDC-recommendations could improve HBV-screening, but with the disadvantage of many tests. Further development of HBV-testing strategies is necessary

Distribution of capsular types and antimicrobial susceptibility of invasive isolates of Streptococcus pneumoniae in Colombian children. Pneumococcal Study Group in Colombia.

PubMed

Castañeda, E; Leal, A L; Castillo, O; De La Hoz, F; Vela, M C; Arango, M; Trujillo, H; Levy, A; Gama, M E; Calle, M; Valencia, M L; Parra, W; Agudelo, N; Mejía, G I; Jaramillo, S; Montoya, F; Porras, H; Sánchez, A; Saa, D; Di Fabio, J L; Homma, A

1997-01-01

Streptococcus pneumoniae is the leading bacterial cause of childhood pneumonia in the developing world. This study describes the type distribution and antimicrobial susceptibility of invasive pneumococcal isolates from Colombian children and is part of the Sistema Regional de Vacunas (SIREVA), a PAHO regional initiative designed to determine the ideal serotype composition of a protein polysaccharide pneumococcal conjugate vaccine for use in children less than 5 years old in Latin America. In Colombia, during the study period, centres in Bogota, Medellin, and Cali collected 324 S. pneumoniae isolates from invasive diseases, 238 (73.5%) from children under the age of 2. Pneumonia was the clinical diagnosis in 41.3% cases, meningitis in 41%, and sepsis in 11.2%. The seven most frequent types included 14(21.9%), 5(10.5%), 23F(9.6%), 1(9%), 6B(9%), 19F(7.1%), and 6A(6.2%). The frequency of diminished susceptibility to penicillin (DSP) was 12%, with 8.9% of isolates showing intermediate level resistance and 3.1% showing high level resistance. Among DSP isolates, 23% were also resistant to cefotaxime, 33.3% to erythromycin, 48.7% to chloramphenicol, and 74.3% to trimethoprim/sulfamethoxazole. Multiple resistance was detected in 59% of the isolates that have DSP. Penicillin resistance was associated with types 23F (53.8%) and 14 (25.6%). These data provides information on capsular types prevalent in Colombia that will not only allow the formulation of an ideal vaccine for the region but also reinforce the need for ongoing regional surveillance.

Impact of the timing of hepatitis B virus identification and anti-hepatitis B virus therapy initiation on the risk of adverse liver outcomes for patients receiving cancer therapy.

PubMed

Hwang, Jessica P; Suarez-Almazor, Maria E; Cantor, Scott B; Barbo, Andrea; Lin, Heather Y; Ahmed, Sairah; Chavez-MacGregor, Mariana; Donato-Santana, Christian; Eng, Cathy; Ferrajoli, Alessandra; Fisch, Michael J; McLaughlin, Peter; Simon, George R; Rondon, Gabriela; Shpall, Elizabeth J; Lok, Anna S

2017-09-01

Data on the incidence of adverse liver outcomes are limited for cancer patients with chronic (hepatitis B surface antigen [HBsAg]-positive/hepatitis B core antibody [anti-HBc]-positive) or past (HBsAg-negative/anti-HBc-positive) hepatitis B virus (HBV) after chemotherapy. This study was aimed at determining the impact of test timing and anti-HBV therapy on adverse liver outcomes in these patients. Patients with solid or hematologic malignancies who received chemotherapy between 2004 and 2011 were retrospectively studied. HBV testing and anti-HBV therapy were defined as early at the initiation of cancer therapy and as late after initiation. Outcomes included hepatitis flares, hepatic impairment, liver failure, and death. Time-to-event analysis was used to determine incidence, and multivariate hazard models were used to determine predictors of outcomes. There were 18,688 study patients (80.4% with solid tumors). The prevalence of chronic HBV was 1.1% (52 of 4905), and the prevalence of past HBV was 7.1% (350 of 4905). Among patients with solid tumors, late identification of chronic HBV was associated with a higher risk of hepatitis flare (hazard ratio [HR], 4.02; 95% confidence interval [CI], 1.26-12.86), hepatic impairment (HR, 8.48; 95% CI, 1.86-38.66), liver failure (HR, 9.38; 95% CI, 1.50-58.86), and death (HR, 3.90; 95% CI, 1.19-12.83) in comparison with early identification. Among patients with hematologic malignancies and chronic HBV, the risk of death was 7.8 (95% CI, 1.73-35.27) times higher for persons with late initiation of anti-HBV therapy versus early initiation. Patients with late identification of chronic HBV had late or no anti-HBV therapy. Chronic HBV predicted liver failure in patients with solid or hematologic malignancies, whereas male sex and late identification were predictors for patients with solid tumors. Early identification correlates with early anti-HBV therapy and reduces the risk of liver failure and death in chronic HBV patients receiving chemotherapy. Cancer 2017;123:3367-76. © 2017 American Cancer Society. © 2017 American Cancer Society.

Investigation of anti-Hepatitis C virus, sofosbuvir and daclatasvir, in pure form, human plasma and human urine using micellar monolithic HPLC-UV method and application to pharmacokinetic study.

PubMed

Zidan, Dalia W; Hassan, Wafaa S; Elmasry, Manal S; Shalaby, Abdalla A

2018-06-01

Simultaneous determination of sofosbuvir (SOF), and daclatasvir (DAC) in their dosage forms, human urine and human plasma using simple and rapid micellar high performance liquid chromatographic method coupled with UV detection (HPLC-UV) had been developed and validated. These drugs are described as co-administered for treatment of Hepatitis C virus (HCV). HCV is the cause of Hepatitis C and some cancers such as liver cancer (hepatocellular carcinoma) and lymphomas in humans. Separation and quantitation were carried out on anonyx™ C 8 monolithic (100 × 4.6 mm (i.d.) analytical column maintained at 25 °C. The mobile phase consisted of 0.1 M sodium dodecyl sulfate (SDS) solution containing 20% (V/V) n-propanolol and 0.3% (V/V) triethylamine and pH was adjusted to 6.5 using 0.02 M phosphoric acid, respectively. The retention times of SOF and DAC were 4.8 min, and 6.5 min, respectively. Measurements were made at flow rate of 0.5 mL/min with injection volume of 20 μL and ultraviolet (UV) detection at 226 nm. Linearity of SOF and DAC was obtained over concentration ranges of 50-400, and 40-400 ng/mL, respectively in pure form, 60-300 and 50-300 ng/mL, respectively for human plasma and over 50-400, and 40-400 ng/mL, respectively for human urine with correlation coefficient >0.999. The proposed method demonstrated excellent intra- and inter-day precision and accuracy. The suggested method was applied for determination of the drugs in pure, dosage form, and in real human plasma, real human urine and drug-dissolution test of their tablets. The obtained results have been statistically compared to reported method to give a conclusion that there is no significant differences. Copyright © 2018 Elsevier B.V. All rights reserved.

A comparative study of cultural methods for the detection of Salmonella in feed and feed ingredients

PubMed Central

Koyuncu, Sevinc; Haggblom, Per

2009-01-01

Background Animal feed as a source of infection to food producing animals is much debated. In order to increase our present knowledge about possible feed transmission it is important to know that the present isolation methods for Salmonella are reliable also for feed materials. In a comparative study the ability of the standard method used for isolation of Salmonella in feed in the Nordic countries, the NMKL71 method (Nordic Committee on Food Analysis) was compared to the Modified Semisolid Rappaport Vassiliadis method (MSRV) and the international standard method (EN ISO 6579:2002). Five different feed materials were investigated, namely wheat grain, soybean meal, rape seed meal, palm kernel meal, pellets of pig feed and also scrapings from a feed mill elevator. Four different levels of the Salmonella serotypes S. Typhimurium, S. Cubana and S. Yoruba were added to each feed material, respectively. For all methods pre-enrichment in Buffered Peptone Water (BPW) were carried out followed by enrichments in the different selective media and finally plating on selective agar media. Results The results obtained with all three methods showed no differences in detection levels, with an accuracy and sensitivity of 65% and 56%, respectively. However, Müller-Kauffmann tetrathionate-novobiocin broth (MKTTn), performed less well due to many false-negative results on Brilliant Green agar (BGA) plates. Compared to other feed materials palm kernel meal showed a higher detection level with all serotypes and methods tested. Conclusion The results of this study showed that the accuracy, sensitivity and specificity of the investigated cultural methods were equivalent. However, the detection levels for different feed and feed ingredients varied considerably. PMID:19192298

Growth dynamics of Salmonella enterica strains on alfalfa sprouts and in waste seed irrigation water.

PubMed

Howard, Michael B; Hutcheson, Steven W

2003-01-01

Alfalfa sprouts and other seed sprouts have been implicated in numerous outbreaks of salmonellosis. The source of these epidemics appears to have been low-level contamination of seeds by Salmonella bacteria that developed into clinically significant populations during the seed germination process. To test the possibility that Salmonella enterica strains carry host range determinants that allow them to grow on alfalfa, strains isolated from alfalfa or other sources were surveyed for their ability to grow on germinating alfalfa seeds. An S. enterica serovar Cubana strain originally isolated from contaminated alfalfa sprouts multiplied most rapidly during the initial 24 h of the seed germination process. Germinating alfalfa seeds supported the multiplication of S. enterica cells prior to the emergence of the root radicle at 72 h. Thereafter, much lower rates of multiplication were apparent. The ability of S. enterica to grow on germinating alfalfa seeds was independent of the serovar, isolation source, or virulence of the strain. Isolates obtained from alfalfa attained population levels similar to those observed for strains isolated from contaminated meat products or stools. Each of the strains could be detected in the waste irrigation water, with populations being strongly correlated with those detected on the germinating alfalfa seeds. The S. enterica strains were capable of utilizing the waste irrigation water as a sole carbon and nitrogen source. S. enterica strains thus appear to grow saprophytically on soluble organics released from seeds during early phases of germination. The ability to detect S. enterica in the waste irrigation water early in the germination process indicates that this method may be used as a simple way to monitor the contamination of sprouts during commercial operations.

High performance liquid chromatography time of flight electrospray ionization mass spectrometry for quantification of sesquiterpenes in Chrysanthemi indici Flos active extract

PubMed Central

Fu, Ling; Wang, Pan; Sun, Yiqun; Wang, Yangyang; Zhao, Jing; Ye, Yuting; Zhang, Yanbin; Bi, Yuefeng

2015-01-01

Background: Chrysanthemi indici Flos, a traditional herbal medicine is used to clearing heat–toxicity, removing the liver fire, and improving eyesight. In our preliminary work, an active extract of CTC in C. An indici Flos with anti-hepatitis B virus and liver protective activity was found by HepG2.2.1.5 test and experiment of protein synthesis in mice's injured liver. In this work, we aimed to study the active faction CTC further by qualitative and quantitative analysis method. Materials and Methods: High performance liquid chromatography time of flight electrospray ionization mass spectrometry (HPLC TOF ESI-MS) analysis method of the CTC was established. Cumambrin A and angeloylcumambrin B in CTC were analyzed by high performance liquid chromatography-ultraviolet-evaporative light scattering detector (HPLC-UV-ELSD) analysis methods. A binary gradient elution program was conducted for chromatographic separation with acetonitrile (A) and ultrapure water (B) as follows: 0–10 min, 42–46% A; 10–20 min, 46–55% A; 20–25 min, 55–60% A; and 25–35 min, 60–75% A. The column temperature and UV wavelength were set at 30°C and 205 nm. Result: Ten constituents including (3R, 5R, 6S, 7S, 10R)-7-(2-hydroxy-2-propyl)-10-methyl-4-methyleneperhy, dronaphthal-ene-3, 5, 6-triol acetone solvate; (+)-edusmance-4, (14)-ene-11, 13-diol; linarin; luteolin; apigenin; tricin; 5, 3’,4’- trimethyl-6,7-dimethoxy flavones; cumambrin A; acacetin; and angeloylcumambrin B in CTC were identified by HPLC TOF ESI-MS. The contents of sesquiterpenes in CTC were decreased by storing years. Conclusions: The results showed that both UV and ELSD methods were feasible, accurate, and the determination results were in good consistency. The contents of two sesquiterpenes decreased with storing years. Two sesquiterpenes could be used as quality control for C. indici flos CTC. PMID:26600718

Vaccination and autoimmunity-'vaccinosis': a dangerous liaison?

PubMed

Shoenfeld, Y; Aron-Maor, A

2000-02-01

The question of a connection between vaccination and autoimmune illness (or phenomena) is surrounded by controversy. A heated debate is going on regarding the causality between vaccines, such as measles and anti-hepatitis B virus (HBV), and multiple sclerosis (MS). Brain antibodies as well as clinical symptoms have been found in patients vaccinated against those diseases. Other autoimmune illnesses have been associated with vaccinations. Tetanus toxoid, influenza vaccines, polio vaccine, and others, have been related to phenomena ranging from autoantibodies production to full-blown illness (such as rheumatoid arthritis (RA)). Conflicting data exists regarding also the connection between autism and vaccination with measles vaccine. So far only one controlled study of an experimental animal model has been published, in which the possible causal relation between vaccines and autoimmune findings has been examined: in healthy puppies immunized with a variety of commonly given vaccines, a variety of autoantibodies have been documented but no frank autoimmune illness was recorded. The findings could also represent a polyclonal activation (adjuvant reaction). The mechanism (or mechanisms) of autoimmune reactions following immunization has not yet been elucidated. One of the possibilities is molecular mimicry; when a structural similarity exists between some viral antigen (or other component of the vaccine) and a self-antigen. This similarity may be the trigger to the autoimmune reaction. Other possible mechanisms are discussed. Even though the data regarding the relation between vaccination and autoimmune disease is conflicting, it seems that some autoimmune phenomena are clearly related to immunization (e.g. Guillain-Barre syndrome). The issue of the risk of vaccination remains a philosophical one, since to date the advantages of this policy have not been refuted, while the risk for autoimmune disease has not been irrevocably proved. We discuss the pros and cons of this

Microbial and chemical transformation studies of the bioactive marine sesquiterpenes (S)-(+)-curcuphenol and -curcudiol isolated from a deep reef collection of the Jamaican sponge Didiscus oxeata.

PubMed

El Sayed, Khalid A; Yousaf, Muhammad; Hamann, Mark T; Avery, Mitchell A; Kelly, Michelle; Wipf, Peter

2002-11-01

.I. >2.6) and 2900 (S.I. >1.6) ng/mL, respectively. Compound 14 shows anti-hepatitis B virus activity with an EC(50) of 61 microg/mL.

Current State of and Needs for Hepatitis B Screening: Results of a Large Screening Study in a Low-Prevalent, Metropolitan Region

PubMed Central

Bottero, Julie; Boyd, Anders; Lemoine, Maud; Carrat, Fabrice; Gozlan, Joel; Collignon, Anne; Boo, Nicolas; Dhotte, Philippe; Varsat, Brigitte; Muller, Gerard; Cha, Olivier; Valin, Nadia; Nau, Jean; Campa, Pauline; Silbermann, Benjamin; Bary, Marc; Girard, Pierre-Marie; Lacombe, Karine

2014-01-01

Background In low hepatitis B virus (HBV)-prevalent countries, most HBV-infected persons are unaware of their status. We aimed to evaluate whether (i) previous HBV-testing, (ii) physicians decision to screen, and (iii) CDC's recommendations identified infected individuals and which risk-factor groups needing testing. Methods During a mass, multi-center HBV-screening study from September 2010-August 2011, 3929 participants were screened for hepatitis B surface antigen (HBsAg), anti-HBs and anti-Hepatitis B core antibodies (anti-HBcAb). Questions on HBV risk-factors and testing practices were asked to participants, while participants' eligibility for HBV-testing was asked to study medical professionals. Results 85 (2.2%) participants were HBsAg-positive, while 659 (16.8%) had either resolved HBV infection or isolated anti-HBcAb. When comparing practices, HBV-testing was more likely to occur in HBV-infected participants if Centers for Disease Control and Prevention (CDC) recommendations were used (Sensitivity = 100%, 95%CI: 95.8–100) than physicians' discretion (Sensitivity = 87.1%, 95%CI: 78.0–93.4) or previous HBV-test (Sensitivity = 36.5%, 95%CI: 26.3–47.6) (p<0.0001). Nevertheless, many non-infected individuals would still have been screened using CDC-recommendations (Specificity = 31.1%, 95%CI: 29.6–32.6). Using multivariable logistic regression, HBsAg-positive status was significantly associated with the following: males, originating from high HBV-endemic region, contact with HBV-infected individual, without national healthcare, and intravenous-drug user (IDU). Of these risk-factors, physician's discretion for testing HBV was not significantly associated with participants' geographical origin or IDU. Conclusions Missed opportunities of HBV-screening are largely due to underestimating country of origin as a risk-factor. Applying CDC-recommendations could improve HBV-screening, but with the disadvantage of many tests. Further development of

[Preliminary analysis on relationship between traditional efficacy of Chinese medicine and modern pharmacological action].

PubMed

Ren, Jun-Guo; Wang, Dong-Zhi; Lei, Lei; Kang, Li; Liu, Jian-Xun

2017-05-01

To find the relationship between traditional efficacy of Chinese medicine and modern pharmacological action by using data mining, and provide information and reference for further research and development for the pharmacology research of traditional Chinese medicine.The information of 547 kinds of traditional Chinese medicines, 335 kinds of Chinese medicine effects and 86 kinds of pharmacological actions were collected and processed in Clinical Guide to the Chinese Pharmacopoeia published in 2010; Access and Excel software were used to analyze the frequence and frequency of single effect, pharmacological action, and both. In addition, the relationship between efficacy and pharmacology was analyzed with the clearing heat and antibacterial effects as the example. The analysis results showed that 547 kinds of Chinese medicines involved 335 kinds of Chinese medicine effects and 86 kinds of pharmacological actions. Among them, the most frequent Chinese medicine effect was"clearing heat", whose frequence was 130 and the frequency was 0.24; the most frequent pharmacological action was "anti-inflammatory action" whose frequence was 191 and the frequency was 0.35. The most common efficacy-pharmacological action group was "clearing heat" and "anti-bacterial action", whose frequence was 75 and the frequency was 0.26. The couple of "purgation" and "cathartic effect" had the largest frequency of 0.30, but they just appeared together for 3 times. There were 52 kinds of pharmacological actions that occurred together with clearing heat, of which, the top 10 were anti-bacterial action, anti-inflammatory action, antineoplastic action, anti-hepatic injury action, immunoregulation action, antipyretic action, antiviralaction, hypoglycemic action, antioxidant action and analgesic action. There were 161 kinds of Chinese medicine effects that occurred together with anti-bacterial action, of which, the top 10 were clearing heat, detoxification, detumescence, analgesia, resolving dampness

Molecular characterization of hepatitis A virus strains in a tertiary care health set up in north western India

PubMed Central

Singh, Mini Pritam; Majumdar, Manasi; Thapa, Babu Ram; Gupta, Puneet Kumar; Khurana, Jasmine; Budhathoki, Bimal; Ratho, Radha Kanta

2015-01-01

Background & objectives: Hepatitis A virus usually causes acute viral hepatitis (AVH) in the paediatric age group with a recent shift in age distribution and disease manifestations like acute liver failure (ALF). This has been attributed to mutations in 5’non-translated region (5’NTR) which affects the viral multiplication. The present study was aimed to carry out the molecular detection and phylogenetic analysis of hepatitis A virus strains circulating in north western India. Methods: Serum samples from in patients and those attending out patient department of Pediatric Gastroenterology in a tertiary care hospital in north India during 2007-2011 with clinically suspected AVH were tested for anti-hepatitis A virus (HAV) IgM antibodies. Acute phase serum samples were subjected to nested PCR targeting the 5’NTR region followed by sequencing of the representative strains. Results: A total of 1334 samples were tested, 290 (21.7%) were positive for anti-HAV IgM antibody. Of these, 78 serum samples (< 7 days old) were subjected to PCR and 47.4% (37/78) samples showed the presence of HAV RNA. Children < 15 yr of age accounted for majority (94%) of cases with highest seropositivity during rainy season. Sequencing of 15 representative strains was carried out and the circulating genotype was found to be III A. The nucleotide sequences showed high homology among the strains with a variation ranging from 0.1-1 per cent over the years. An important substitution of G to A at 324 position was shown by both AVH and ALF strains. The cumulative substitution in AVH strains Vs ALF strains as compared to GBM, Indian and prototype strain in the 200-500 region of 5’ NTR was comparable. Interpretation & conclusion: Our results showed hepatitis A still a disease of children with III A as a circulating genotype in this region. The mutations at 5’NTR region warrant further analysis as these affect the structure of internal ribosomal entry site which is important for viral

Molecular characterization of hepatitis A virus strains in a tertiary care health set up in north western India.

PubMed

Singh, Mini Pritam; Majumdar, Manasi; Thapa, Babu Ram; Gupta, Puneet Kumar; Khurana, Jasmine; Budhathoki, Bimal; Ratho, Radha Kanta

2015-02-01

Hepatitis A virus usually causes acute viral hepatitis (AVH) in the paediatric age group with a recent shift in age distribution and disease manifestations like acute liver failure (ALF). This has been attributed to mutations in 5'non-translated region (5'NTR) which affects the viral multiplication. The present study was aimed to carry out the molecular detection and phylogenetic analysis of hepatitis A virus strains circulating in north western India. Serum samples from in patients and those attending out patient department of Pediatric Gastroenterology in a tertiary care hospital in north India during 2007-2011 with clinically suspected AVH were tested for anti-hepatitis A virus (HAV) IgM antibodies. Acute phase serum samples were subjected to nested PCR targeting the 5'NTR region followed by sequencing of the representative strains. A total of 1334 samples were tested, 290 (21.7%) were positive for anti-HAV IgM antibody. Of these, 78 serum samples (< 7 days old) were subjected to PCR and 47.4% (37/78) samples showed the presence of HAV RNA. Children < 15 yr of age accounted for majority (94%) of cases with highest seropositivity during rainy season. Sequencing of 15 representative strains was carried out and the circulating genotype was found to be III A. The nucleotide sequences showed high homology among the strains with a variation ranging from 0.1-1 per cent over the years. An important substitution of G to A at 324 position was shown by both AVH and ALF strains. The cumulative substitution in AVH strains Vs ALF strains as compared to GBM, Indian and prototype strain in the 200-500 region of 5' NTR was comparable. Our results showed hepatitis A still a disease of children with III A as a circulating genotype in this region. The mutations at 5'NTR region warrant further analysis as these affect the structure of internal ribosomal entry site which is important for viral replication.

Epidemic and sporadic hepatitis E virus transmission in West Kalimantan (Borneo), Indonesia.

PubMed

Corwin, A; Putri, M P; Winarno, J; Lubis, I; Suparmanto, S; Sumardiati, A; Laras, K; Tan, R; Master, J; Warner, G; Wignall, F S; Graham, R; Hyams, K C

1997-07-01

A cross-sectional survey was conducted in West Kalimantan (Borneo), Indonesia to geographically profile hepatitis E virus (HEV) prevalence in the riverine areas recognized as the foci of epidemic HEV transmission in 1987. Additionally, a contiguous, although distinct, population with no identifiable historical exposure to epidemic HEV was surveyed downstream for comparative purposes. Eight hundred eighty-five sera were assayed by enzyme immunoabsorbent assay for anti-HEV IgG and anti-hepatitis A virus (HAV) IgG markers. A very high percent (90%) of both the outbreak and comparison populations was anti-HAV IgG positive by the age of nine years. In contrast, the prevalence of anti-HEV IgG in the outbreak area (50%) was significantly higher than in the comparison area (23%) (P < 0.0001). In both the outbreak and comparison areas, anti-HEV IgG prevalence increased with age ( < 0.0001), except for the group > or = 50 years of age. The prevalence (53%) of antibody to HEV in the population > or = seven years of age from the outbreak area (alive during the actual 1987 outbreak) was significantly (P < 0.0001) greater than among the children < seven years of age (born after the outbreak) (15%). However, anti-HEV IgG prevalence among the population from the comparison area did not differ significantly between the > or = seven- (23%) and < seven- (20%) year-old age groups. The percentage of anti-HEV IgG-positive individuals among males (47%) from the outbreak area was lower (P < 0.05) compared with females (55%). While overall usage of river water for drinking purposes was not universal, dependence on river water as a primary source was significantly higher (P < 0.001) in households from the outbreak area (60%) compared with the comparison area (30%). This study indicates persistence of an anti-HEV IgG response in a large percentage of the population seven years after an epidemic of HEV infections. Also, the relatively high prevalence (15%) of anti-HEV in children < seven

Persistence of antibodies 20 y after vaccination with a combined hepatitis A and B vaccine

PubMed Central

Van Damme, Pierre; Leroux-Roels, Geert; Suryakiran, P.; Folschweiller, Nicolas; Van Der Meeren, Olivier

2017-01-01

ABSTRACT Vaccination is the most effective and well-tolerated method of conferring long-term protection against hepatitis A and B viruses (HAV; HBV). Long-term studies are required to characterize the duration of protection and need for boosters. Following primary immunization of 150 and 157 healthy adults with 3-doses of combined hepatitis A/hepatitis B vaccine (HAB; Twinrix™, GSK Vaccines, Belgium) at 0-1-6 months in 2 separate studies, we measured vaccine-induced antibody persistence against HAV and HBV annually for 20 y (Study A: NCT01000324; Study B: NCT01037114). Subjects with circulating anti-HAV antibodies < 15 mIU/mL or with anti-hepatitis B surface antigen < 10 mIU/mL were offered an additional monovalent hepatitis A and/or B vaccine dose (Havrix™/Engerix™-B, GSK Vaccines, Belgium). Applying the immunogenicity results from these studies, mathematical modeling predicted long-term persistence. After 20 y, 18 and 25 subjects in studies A and B, respectively, comprised the long-term according-to-protocol cohort for immunogenicity; 100% and 96.0% retained anti-HAV antibodies ≥ 15 mIU/mL, respectively; 94.4% and 92.0% had anti-HBs antibodies ≥ 10 mIU/mL, respectively. Between Years 16–20, 4 subjects who received a challenge dose of monovalent hepatitis A vaccine (N = 2) or hepatitis B vaccine (N = 2), all mounted a strong anamnestic response suggestive of immune memory despite low antibody levels. Mathematical modeling predicts that 40 y after vaccination ≥ 97% vaccinees will maintain anti-HAV ≥ 15 mIU/mL and ≥ 50% vaccinees will retain anti-HBs ≥ 10 mIU/mL. Immunogenicity data confirm that primary immunization with 3-doses of HAB induces persisting anti-HAV and anti-HBs specific antibodies in most adults for up to 20 y; mathematical modeling predicts even longer-term protection. PMID:28281907

Persistence of antibodies 20 y after vaccination with a combined hepatitis A and B vaccine.

PubMed

Van Damme, Pierre; Leroux-Roels, Geert; Suryakiran, P; Folschweiller, Nicolas; Van Der Meeren, Olivier

2017-05-04

Vaccination is the most effective and well-tolerated method of conferring long-term protection against hepatitis A and B viruses (HAV; HBV). Long-term studies are required to characterize the duration of protection and need for boosters. Following primary immunization of 150 and 157 healthy adults with 3-doses of combined hepatitis A/hepatitis B vaccine (HAB; Twinrix™, GSK Vaccines, Belgium) at 0-1-6 months in 2 separate studies, we measured vaccine-induced antibody persistence against HAV and HBV annually for 20 y (Study A: NCT01000324; Study B: NCT01037114). Subjects with circulating anti-HAV antibodies < 15 mIU/mL or with anti-hepatitis B surface antigen < 10 mIU/mL were offered an additional monovalent hepatitis A and/or B vaccine dose (Havrix™/Engerix™-B, GSK Vaccines, Belgium). Applying the immunogenicity results from these studies, mathematical modeling predicted long-term persistence. After 20 y, 18 and 25 subjects in studies A and B, respectively, comprised the long-term according-to-protocol cohort for immunogenicity; 100% and 96.0% retained anti-HAV antibodies ≥ 15 mIU/mL, respectively; 94.4% and 92.0% had anti-HBs antibodies ≥ 10 mIU/mL, respectively. Between Years 16-20, 4 subjects who received a challenge dose of monovalent hepatitis A vaccine (N = 2) or hepatitis B vaccine (N = 2), all mounted a strong anamnestic response suggestive of immune memory despite low antibody levels. Mathematical modeling predicts that 40 y after vaccination ≥ 97% vaccinees will maintain anti-HAV ≥ 15 mIU/mL and ≥ 50% vaccinees will retain anti-HBs ≥ 10 mIU/mL. Immunogenicity data confirm that primary immunization with 3-doses of HAB induces persisting anti-HAV and anti-HBs specific antibodies in most adults for up to 20 y; mathematical modeling predicts even longer-term protection.

Postoperative Outcomes for Patients with Non-B Non-C Hepatocellular Carcinoma: A Subgroup Analysis of Patients with a History of Hepatitis B Infection.

PubMed

Omichi, Kiyohiko; Shindoh, Junichi; Yamamoto, Satoshi; Matsuyama, Yutaka; Akamatsu, Nobuhisa; Arita, Junichi; Kaneko, Junichi; Sakamoto, Yoshihiro; Hasegawa, Kiyoshi; Kokudo, Norihiro

2015-12-01

Hepatocellular carcinoma (HCC) not associated with active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, termed non-B non-C HCC (nBnC-HCC), is reportedly correlated with better survival outcomes than HBV- or HCV-related HCC. However, the nBnC-HCC population includes patients with a history of HBV infection possessing anti-hepatitis B core antibodies (HBcAb), and the oncologic significance of this finding remains unclear. A retrospective review of the data for 562 patients who underwent curative resection for primary HCC was performed. The clinical outcomes were compared among the following four groups: HBV group (HBsAg-positive), HCV group (HCVAb-positive), HBcAb-positive nBnC-HCC group, and pure nBnC-HCC group (negative for these viral markers). The HBcAb-positive nBnC-HCC group showed better overall survival (OS) and recurrence-free survival (RFS) rates than the HBV, HCV, and pure nBnC-HCC groups (5-year OS 89.4 vs 68.4, 62.0, and 66.2 %; P = 0.003; 5-year RFS 53.8 vs 31.4, 28.1, and 33.6 %; P = 0.01). A multivariate analysis confirmed that a history of HBV is associated with a lower risk of OS (hazard ratio [HR] 0.23; 95 % confidence interval [CI] 0.09-0.56; P = 0.001) and RFS (HR 0.45; 95 % CI 0.27-0.73; P = 0.001). The HBcAb-positive nBnC-HCC group was associated with a higher incidence of well-differentiated HCC (33 vs 15 %; P = 0.03) and lower plasma des-gamma-carboxyprothrombin concentration (72 vs 357 mAu/mL; P = 0.047) than the pure nBnC group. The subgroup of patients with a history of HBV infection may have better survival outcomes after resection of HCC than the HBV/HCV-related or pure nBnC-HCC patients.

Changing trends in serotypes of S. pneumoniae isolates causing invasive and non-invasive diseases in unvaccinated population in Mexico (2000-2014).

PubMed

Carnalla-Barajas, María Noemí; Soto-Noguerón, Araceli; Sánchez-Alemán, Miguel Angel; Solórzano-Santos, Fortino; Velazquez-Meza, María Elena; Echániz-Aviles, Gabriela

2017-05-01

Introduction of pneumococcal conjugate vaccines (PCV) targeted against a limited number of serotypes substantially decreased invasive (IPD) and non-invasive pneumococcal diseases (NIPD) but it was accompanied by non-vaccine type replacement disease. After 9 years of introduction of PCV in Mexico, we analyze the evidence of the indirect effects on IPD and NIPD serotype distribution among groups not targeted to receive the vaccine. From January 2000 to December 2014, pneumococcal strains isolated from IPD and NIPD cases from patients ≥5 years of age from participant hospitals of the SIREVA II (Sistema Regional de Vacunas) network were serotyped. A regression analysis was performed considering year and proportion of serotypes included in the different vaccine formulations (PCV7, PCV10 and PCV13). The slope was obtained for each regression line and their correspondent p-value. The proportion of each serotype in the pre-PCV7 and post-PCV7 periods was evaluated by χ2 test. From a total of 1147 pneumococcal strains recovered, 570 corresponded to the pre-PCV7 and 577 to the post-PCV7 periods. The proportion of vaccine serotypes included in the three PCV formulations decreased by 2.4, 2.6 and 1.3%, respectively per year during the study period. A significant increase of serotype 19A was observed in the post-vaccine period in all age groups. A percentage of annual decline of serotypes causing IPD and NIPD included in PCV was detected among groups not targeted to receive the vaccine, probably due to herd effect. Considering pneumococcal serotype distribution is a dynamic process, we highlight the importance of surveillance programs. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Seroprevalence of hepatitis B and C viruses among medical waste handlers at Gondar town Health institutions, Northwest Ethiopia

PubMed Central

2012-01-01

Background Viral hepatitis is an inflammation of the liver due to viral infections and there are groups of viruses that affects the liver of which hepatitis B and C viruses are the causative agents of sever form of liver disease with high rate of mortality. Medical waste handlers who undergo collection, transportation, and disposal of medical wastes in the health institutions are at risk of exposure to acquire those infections which transmit mainly as a result of contaminated blood and other body fluids including injury with sharp instruments, splash to the eye or mucous membrane. This study aimed to determine the prevalence of hepatitis B and/or C viruses and associated risk factors among medical waste handlers. Results A cross-sectional study was conducted from April, 2011 to June, 2011 in government health institutions at Gondar town. Socio-demographic and possible risk factors data from medical waste handlers were collected using pre-tested and well structured questionnaires. Venous bloods were collected and the serums were tested for hepatitis B surface antigen and anti-hepatitis C antibody using rapid Immunochromatography assay. Data was entered and analyzed using SPSS software package (version16). Chi-square and Fisher exact tests were used to assess risk of association. A p-value of < 0.05 was considered statistical significance. A total of 100 medical waste handlers and 100 non-clinical waste handlers were examined for HBV and HCV viruses. HBV was detected in 6 (6.0%) and 1 (1.0%) and HCV in 1 (1.0%) and 0 (0.0%) of medical waste handlers and non-clinical waste handlers, respectively. Significant differences were observed in the detection rates of HBV (OR = 6.3; X2 = 4.1; P = 0.04) and overall infection rate (HBV + HCV) (OR = 7.5; X2 = 5.2; P: 0.02) in medical waste handlers when compared with non-clinical waste handlers. It was found that none of the observed risk factors significantly associated with rate of hepatitis infection compared to others

A randomized trial of alternative two- and three-dose hepatitis B vaccination regimens in adolescents: antibody responses, safety, and immunologic memory.

PubMed

Cassidy, W M; Watson, B; Ioli, V A; Williams, K; Bird, S; West, D J

2001-04-01

Hoping to increase hepatitis B (HB) vaccination of adolescents, we did the following: 1) studied if modified regimens of the recombinant HB vaccine, Recombivax HB (2 or 3 doses of 5 or 10 microg given over 4 or 6 months), induce protective anti-hepatitis B surface antibody [anti-HBsAb] levels (>/=10 mIU/mL) comparable to the recommended regimen (5 microg at 0 and 1, and 6 months); 2) measured early antibody response after a single dose; and 3) assessed immunologic memory after 2- and 3-dose regimens. One thousand twenty-six adolescents were randomized to 1 of 5 treatment groups (10 microg at 0 and 4 or 0 and 6 months; 5 microg at 0 and 6 or 0, 2, and 4 or 0, 1, and 6 months) in an open trial. Anti-HBsAb was measured in all participants just before and 1 month after the last dose, and at several other times in a subset of vaccinees. Anti-HBsAb response to a booster dose 2 years later was examined to assess immunologic memory in participants vaccinated with 5 microg at 0 and 6 or 0, 1, and 6 months. All regimens induced >/=10 mIU/mL of anti-HBs in >/=95% of vaccinees. Geometric mean titers ranged from 674.8 to 3049.4 mIU/mL. Geometric mean titers were higher with regimens using the following: 1) 10 versus 5 microg; 2) 3 versus 2 doses; and 3) vaccination intervals of 6 versus 4 months. After 6 months, 63.8% of vaccinees given one 10-microg dose had >/=10 mIU/mL of anti-HBsAb versus 41.6% after one 5-microg dose. Participants vaccinated with either two or three 5-microg doses retained robust immunologic memory. . The results of this study show that a 2-dose regimen of Recombivax HB is as immunogenic and induces immunologic memory as effectively as the recommended 3-dose regimen. A regimen of two 10-microg doses may be of significant benefit for vaccinees who are poorly compliant or deviate from the intended vaccination schedule.

Using UHPLC and UV-vis Fingerprint Method to Evaluate Substitutes for Swertia mileensis: An Endangered Medicinal Plant.

PubMed

Li, Jie; Zhang, Ji; Jin, Hang; Wang, Yuan-Zhong; Huang, Heng-Yu

2017-01-01

exist are in leaves of S. davidii with the highest content.The obvious diversity in four plants was displayed from comprehensive point of view though similarity assay and PCA analysis.The UV fingerprint method offsets the defect that the UHPLC fingerprint reflected messages of secoiridoid glycosides only. Abbreviation used: UHPLC: Ultra high performance liquid chromatography, UV-vis: Ultraviolet-vis, HBV: Anti-hepatitis virus, DNA: Deoxyribonucleic acid, PCA: Principal component analysis, D-GaIN: D-Galactosamine, BCG: Bacille Calmette-Guerin, LPS: Lipopolysaccharide.

Differences in capabilities of different enzyme immunoassays to detect anti-hepatitis E virus immunoglobulin G in pigs infected experimentally with hepatitis E virus genotype 3 or 4 and in pigs with unknown exposure.

PubMed

Zhang, H; Mohn, U; Prickett, J R; Schalk, S; Motz, M; Halbur, P G; Feagins, A R; Meng, X J; Opriessnig, T

2011-08-01

Hepatitis E virus (HEV), a major cause of acute viral hepatitis in humans in many developing countries, is highly prevalent in the pig population worldwide. The objective of this study was to assess the capability of three porcine prototypes of a human enzyme-linked immunosorbent assay (ELISA), an in-house ELISA and a line-immunoassay (LIA) to detect anti-HEV antibodies in pigs infected experimentally with HEV (n = 57), known to be negative for HEV infection (n = 27), or with unknown exposure to HEV infection (field samples, n = 90). All 27 samples from non-infected pigs were negative with all five assays. The earliest detection of anti-HEV antibodies occurred at 14 days post-inoculation (dpi) with four of five assays. From 42 dpi, all samples from infected pigs were detected correctly as anti-HEV positive. Kappa analysis demonstrated substantial agreement among tests (0.62-1.00) at 14 dpi and complete agreement (1.00) at 56 dpi. The overall area under the curve for all quantitative tests as determined by receiver operator characteristic analysis ranged from 0.794 to 0.831 indicating moderate accuracy. The results showed that all five assays can detect anti-HEV IgG antibodies accurately in pigs infected experimentally with HEV. In field samples, a higher prevalence of anti-HEV IgG was found in breeding herds than in growing pigs (100% versus 66.7-93.9%). These serological assays should be very useful in veterinary diagnostic labs for HEV diagnosis in swine. Copyright © 2011 Elsevier B.V. All rights reserved.

Anti-hepatitis B core antigen testing with detection and characterization of occult hepatitis B virus by an in-house nucleic acid testing among blood donors in Behrampur, Ganjam, Orissa in southeastern India: implications for transfusion

PubMed Central

2010-01-01

Background Occult hepatitis B virus (HBV) infection might transmit viremic units into the public blood supply if only hepatitis B surface antigen (HBsAg) testing is used for donor screening. Our aim was to evaluate the prevalence of occult HBV infection among the HBsAg negative/antiHBc positive donations from a highly HIV prevalent region of India. Methods A total of 729 HBsAg negative donor units were included in this study. Surface gene and precore region were amplified by in house nucleic acid test (NAT) for detection of occult HBV infection and surface gene was analyzed after direct sequencing. Results A total of 220 (30.1%) HBsAg negative donors were antiHBc positive, of them 66 (30%) were HBV DNA positive by NAT. HBV DNA positivity among 164 antiHBc only group, was 27.1% and among 40 antiHBs positive group was 30.0%. HBV/D (93.3%) was predominant and prevalence of both HBV/C and HBV/A was 3.3%. Single or multiple amino acids substitutions were found in 95% samples. Conclusion Thus, a considerable number of HBV infected donors remain undiagnosed, if only HBsAg is used for screening. Addition of antiHBc testing for donor screening, although will lead to rejection of a large number of donor units, will definitely eliminate HBV infected donations and help in reducing HBV transmission with its potential consequences, especially among the immunocompromised population. The HBV genetic diversity found in this donor population are in accordance with other parts of India. PMID:20799931

Anti-hepatitis B core antigen testing with detection and characterization of occult hepatitis B virus by an in-house nucleic acid testing among blood donors in Behrampur, Ganjam, Orissa in southeastern India: implications for transfusion.

PubMed

Panigrahi, Rajesh; Biswas, Avik; Datta, Sibnarayan; Banerjee, Arup; Chandra, Partha K; Mahapatra, Pradip K; Patnaik, Bharat; Chakrabarti, Sekhar; Chakravarty, Runu

2010-08-27

Occult hepatitis B virus (HBV) infection might transmit viremic units into the public blood supply if only hepatitis B surface antigen (HBsAg) testing is used for donor screening. Our aim was to evaluate the prevalence of occult HBV infection among the HBsAg negative/antiHBc positive donations from a highly HIV prevalent region of India. A total of 729 HBsAg negative donor units were included in this study. Surface gene and precore region were amplified by in house nucleic acid test (NAT) for detection of occult HBV infection and surface gene was analyzed after direct sequencing. A total of 220 (30.1%) HBsAg negative donors were antiHBc positive, of them 66 (30%) were HBV DNA positive by NAT. HBV DNA positivity among 164 antiHBc only group, was 27.1% and among 40 antiHBs positive group was 30.0%. HBV/D (93.3%) was predominant and prevalence of both HBV/C and HBV/A was 3.3%. Single or multiple amino acids substitutions were found in 95% samples. Thus, a considerable number of HBV infected donors remain undiagnosed, if only HBsAg is used for screening. Addition of antiHBc testing for donor screening, although will lead to rejection of a large number of donor units, will definitely eliminate HBV infected donations and help in reducing HBV transmission with its potential consequences, especially among the immunocompromised population. The HBV genetic diversity found in this donor population are in accordance with other parts of India.

[Low-molecular-weight regulators of biogenic polyamine metabolism affect cytokine production and expression of hepatitis С virus proteins in Huh7.5 human hepatocarcinoma cells].

PubMed

Masalova, O V; Lesnova, E I; Samokhvalov, E I; Permyakova, K Yu; Ivanov, A V; Kochetkov, S N; Kushch, A A

2017-01-01

to a lesser extent. Incubation with DFMO led to a 28-32% decrease in the number of cells expressing NS5B or NS5A, both of which are key components of the HCV replication complex. The results obtained in the work indicate that a further detailed study of the antiviral activity of DFMO is required in order to assess its potential as an anti-hepatitis C therapeutic agent.

Hepatitis C in pregnancy: screening, treatment, and management.

PubMed

Hughes, Brenna L; Page, Charlotte M; Kuller, Jeffrey A

2017-11-01

In the United States, 1-2.5% of pregnant women are infected with hepatitis C virus, which carries an approximately 5% risk of transmission from mother to infant. Hepatitis C virus can be transmitted to the infant in utero or during the peripartum period, and infection during pregnancy is associated with increased risk of adverse fetal outcomes, including fetal growth restriction and low birthweight. The purpose of this document is to discuss the current evidence regarding hepatitis C virus in pregnancy and to provide recommendations on screening, treatment, and management of this disease during pregnancy. The following are Society for Maternal-Fetal Medicine recommendations: (1) We recommend that obstetric care providers screen women who are at increased risk for hepatitis C infection by testing for anti-hepatitis C virus antibodies at their first prenatal visit. If initial results are negative, hepatitis C screening should be repeated later in pregnancy in women with persistent or new risk factors for hepatitis C infection (eg, new or ongoing use of injected or intranasal illicit drugs) (GRADE 1B). (2) We recommend that obstetric care providers screen hepatitis C virus-positive pregnant women for other sexually transmitted diseases, including HIV, syphilis, gonorrhea, chlamydia, and hepatitis B virus (GRADE 1B). (3) We suggest that patients with hepatitis C virus, including pregnant women, be counseled to abstain from alcohol (Best Practice). (4) We recommend that direct-acting antiviral regimens only be used in the setting of a clinical trial or that antiviral treatment be deferred to the postpartum period as direct-acting antiviral regimens are not currently approved for use in pregnancy (GRADE 1C). (5) We suggest that if invasive prenatal diagnostic testing is requested, women be counseled that data on the risk of vertical transmission are reassuring but limited; amniocentesis is recommended over chorionic villus sampling given the lack of data on the

Pharmacokinetics and food interaction of a novel prodrug of tenofovir, tenofovir dipivoxil fumarate, in healthy volunteers.

PubMed

Lu, C; Jia, Y; Chen, L; Ding, Y; Yang, J; Chen, M; Song, Y; Sun, X; Wen, A

2013-04-01

Tenofovir dipivoxil fumarate is a novel ester prodrug of tenofovir, a specific anti-hepatitis B virus (HBV) drug candidate. The pharmacokinetic properties and the effects of food intake on tenofovir dipivoxil have not yet been reported in healthy adults. The aim of this study was to evaluate the pharmacokinetic properties and food interaction of tenofovir dipivoxil in healthy Chinese volunteers. Pharmacokinetic studies included an ascending single dose of 150, 300, 600 mg and multiple doses of 300 mg. Food interaction was evaluated following a single oral dose of tenofovir dipivoxil fumarate 300 mg administered with a high-fat and high-energy standard breakfast or after a 12-h fast. Pharmacokinetic parameters of tenofovir given in each treatment period were calculated using non-compartmental analysis. After a single dose of 150, 300 and 600 mg, the main pharmacokinetic parameters for tenofovir were as follows: Cmax 209·6, 456·7, 989·8 ng/mL; AUClast 1744·9, 2663·5, 6010·2 ng h/mL, respectively. After multiple doses of 300 mg, the main pharmacokinetic parameters for tenofovir were Cmax 523·4 ng/mL, AUClast 4152·4 ng h/mL. After a single dose of 300 mg with a high-fat and high-energy standard breakfast, the main pharmacokinetic parameters for tenofovir were Cmax 448·5 ng/mL, AUClast 3286·8 ng h/mL. The plasma Cmax and AUC of tenofovir showed significance difference between a single dose of 300 mg and the accordingly multiple doses (P < 0·05). A standard high-fat meal enhanced mean AUClast values of tenofovir (relative AUClast  = 125·8%; 90% CI 114·5, 136·2); however, food did not show any significant on Cmax (relative Cmax  = 103·4%; 90% CI 94·6, 112·6). Oral tenofovir dipivoxil fumarate produced predictable and dose-proportional plasma tenofovir pharmacokinetics. The accumulation ratio was 1·51, suggesting tenofovir dipivoxil fumarate displayed accumulation after repeated administration. The bioavailability of tenofovir

Using UHPLC and UV-vis Fingerprint Method to Evaluate Substitutes for Swertia mileensis: An Endangered Medicinal Plant

PubMed Central

Li, Jie; Zhang, Ji; Jin, Hang; Wang, Yuan-Zhong; Huang, Heng-Yu

2017-01-01

Swertia.Swertiamarin is the unique common compounds for four plants, which exist are in leaves of S. davidii with the highest content.The obvious diversity in four plants was displayed from comprehensive point of view though similarity assay and PCA analysis.The UV fingerprint method offsets the defect that the UHPLC fingerprint reflected messages of secoiridoid glycosides only. Abbreviation used: UHPLC: Ultra high performance liquid chromatography, UV-vis: Ultraviolet-vis, HBV: Anti-hepatitis virus, DNA: Deoxyribonucleic acid, PCA: Principal component analysis, D-GaIN: D-Galactosamine, BCG: Bacille Calmette-Guerin, LPS: Lipopolysaccharide PMID:28216877

Vaccine-Induced Anti-HBs Level in 5-6 Year-Old Malnourished Children.

PubMed

Karimi, Mehran; Raee, Ali; Baghianimoghadam, Behnam; Fallahzadeh, Mohammad Hossein

2013-02-01

Malnutrition is the most common cause of immune deficiency. It results in reduced secretion of T-cells and B-cell-stimulating factors leading to declining of special immunoglobulins. On the other hand, hepatitis B, as a major world health problem, can be prevented effectively by vaccination. Three doses of hepatitis B virus (HBV) vaccine induce protective levels of anti-hepatitis B surface (anti-HBs) in 95% of healthy children. This level decreases gradually over time. The goal of this study was to assess anti-HBs in malnourished children, who confronted to some degrees of immune deficiency. This is a cross-sectional study conducted during May to August 2010 in therapeutic clinics of Yazd, Iran. Samples were selected simply and consecutively among 5-6 year-old children with a history of three doses of HBV vaccine in infancy. On the basis of World Health Organization's definition on malnutrition, which considers anthropometric measurements, malnourished children entered the study. Totally 83 cases (37 boys and 46 girls) were gathered and classified into three groups of mild, moderate, and severe malnutrition. One milliliter of venous blood was taken and anti-HBs were tested by enzyme linked immunosorbant assay (ELISA). Overall, seroprotection rate and geometric mean titer (GMT) of anti-HBs were 60.2% and 15.47 ± 10.92 mIU/mL, respectively. Seroprotection rate was 71.4%, 55.2%, and 72.7% in mild, moderate, and severe malnourished children, respectively. GMT was 30.78 mIU/mL, 12.15 mIU/mL, and 22.95 mIU/mL in these groups, respectively. None of these two indices were significant in these groups (P = 0.471, P = 0.364). Seroprotection rate and GMT were 54.1% and 13.26 ± 11.59 mIU/mL in boys, and 65.2% and 17.5 ± 10.59 mIU/mL in girls, respectively, showing no significant relationship with gender (P = 0.302, P = 0.602). Lowest seroprotection rate was in stunted cases (47.1%) and highest in wasted children (77.8%). This difference also was not significant (P = 0

Plant-Microbe and Abiotic Factors Influencing Salmonella Survival and Growth on Alfalfa Sprouts and Swiss Chard Microgreens

PubMed Central

Reed, Elizabeth; Ferreira, Christina M.; Bell, Rebecca; Brown, Eric W.

2018-01-01

ABSTRACT Microgreens, like sprouts, are relatively fast-growing products and are generally consumed raw. Moreover, as observed for sprouts, microbial contamination from preharvest sources may also be present in the production of microgreens. In this study, two Salmonella enterica serovars (Hartford and Cubana), applied at multiple inoculation levels, were evaluated for survival and growth on alfalfa sprouts and Swiss chard microgreens by using the most-probable-number (MPN) method. Various abiotic factors were also examined for their effects on Salmonella survival and growth on sprouts and microgreens. Community-level physiological profiles (CLPPs) of sprout/microgreen rhizospheres with different levels of S. enterica inoculation at different growth stages were characterized by use of Biolog EcoPlates. In the seed contamination group, the ability of S. enterica to grow on sprouting alfalfa seeds was affected by both seed storage time and inoculation level but not by serovar. However, the growth of S. enterica on Swiss chard microgreens was affected by serovar and inoculation level. Seed storage time had little effect on the average level of Salmonella populations in microgreens. In the irrigation water contamination group, the growth of Salmonella on both alfalfa sprouts and microgreens was largely affected by inoculation level. Surprisingly, the growth medium was found to play an important role in Salmonella survival and growth on microgreens. CLPP analysis showed significant changes in the microbial community metabolic diversity during sprouting for alfalfa sprouts, but few temporal changes were seen with microgreens. The data suggest that the change in rhizosphere bacterial functional diversity was dependent on the host but independent of Salmonella contamination. IMPORTANCE Sprouts and microgreens are considered “functional foods,” i.e., foods containing health-promoting or disease-preventing properties in addition to normal nutritional values. However, the

Plant-Microbe and Abiotic Factors Influencing Salmonella Survival and Growth on Alfalfa Sprouts and Swiss Chard Microgreens.

PubMed

Reed, Elizabeth; Ferreira, Christina M; Bell, Rebecca; Brown, Eric W; Zheng, Jie

2018-05-01

Microgreens, like sprouts, are relatively fast-growing products and are generally consumed raw. Moreover, as observed for sprouts, microbial contamination from preharvest sources may also be present in the production of microgreens. In this study, two Salmonella enterica serovars (Hartford and Cubana), applied at multiple inoculation levels, were evaluated for survival and growth on alfalfa sprouts and Swiss chard microgreens by using the most-probable-number (MPN) method. Various abiotic factors were also examined for their effects on Salmonella survival and growth on sprouts and microgreens. Community-level physiological profiles (CLPPs) of sprout/microgreen rhizospheres with different levels of S. enterica inoculation at different growth stages were characterized by use of Biolog EcoPlates. In the seed contamination group, the ability of S. enterica to grow on sprouting alfalfa seeds was affected by both seed storage time and inoculation level but not by serovar. However, the growth of S. enterica on Swiss chard microgreens was affected by serovar and inoculation level. Seed storage time had little effect on the average level of Salmonella populations in microgreens. In the irrigation water contamination group, the growth of Salmonella on both alfalfa sprouts and microgreens was largely affected by inoculation level. Surprisingly, the growth medium was found to play an important role in Salmonella survival and growth on microgreens. CLPP analysis showed significant changes in the microbial community metabolic diversity during sprouting for alfalfa sprouts, but few temporal changes were seen with microgreens. The data suggest that the change in rhizosphere bacterial functional diversity was dependent on the host but independent of Salmonella contamination. IMPORTANCE Sprouts and microgreens are considered "functional foods," i.e., foods containing health-promoting or disease-preventing properties in addition to normal nutritional values. However, the microbial

Estimación de la Relación Costo-Efectividad de las Vacunas Neumocócicas Conjugadas Prevenar-13 y Synflorix®, Utilizadas en Los Programas de Vacunación de Población Infantil Mexicana.

PubMed

Gómez, Jorge A; Villaseñor-Sierra, Alberto; Aguilar, Gerardo Martínez; Manjarrez, Roberto Carreño; Cervantes-Apolinar, María Y

2016-12-01

To estimate the cost effectiveness associated with the use of pneumococcal conjugated vaccines, Prevenar-13 and Synflorix®, in the Mexican pediatric population. The cost-effectiveness ratio of instrumenting vaccination programs based upon the use of Prevenar-13 and Synflorix® in the Mexican pediatric population was estimated by using a Markov's simulation model. The robustness of the conclusions reached on cost-effectiveness for both vaccines was assayed through an univariate and probabilistic sensitivity analysis that included all of the parameters considered by the model. Synflorix® was dominant over Prevenar-13 in the cost-utility analysis; the former generated more quality-adjusted life years at a lower cost and with a lower incremental cost-utility ratio. Based on the cost-effective analysis, Prevenar-13 generated more life years gained but at a higher cost. The use of Prevenar-13 originated a higher incremental cost-effectiveness ratio and, therefore, it was not cost-effective as compared with Synflorix®. Even though the simulations for Prevenar-13 and Synflorix® revealed both of them to be cost-effective when used to instrument pediatric vaccination campaigns in Mexico, Synflorix® had a better cost-utility/effectiveness profile. In addition, although Prevenar-13 and Synflorix® produced equivalent health outcomes, the overall analysis predicted that Synflorix® would save 360 million Mexican pesos, as compared with Prevenar-13. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Vaccine-Induced Anti-HBs Level in 5-6 Year-Old Malnourished Children

PubMed Central

Karimi, Mehran; Raee, Ali; Baghianimoghadam, Behnam; Fallahzadeh, Mohammad Hossein

2013-01-01

Background Malnutrition is the most common cause of immune deficiency. It results in reduced secretion of T-cells and B-cell-stimulating factors leading to declining of special immunoglobulins. On the other hand, hepatitis B, as a major world health problem, can be prevented effectively by vaccination. Three doses of hepatitis B virus (HBV) vaccine induce protective levels of anti-hepatitis B surface (anti-HBs) in 95% of healthy children. This level decreases gradually over time. Objectives The goal of this study was to assess anti-HBs in malnourished children, who confronted to some degrees of immune deficiency. Patients and Methods This is a cross-sectional study conducted during May to August 2010 in therapeutic clinics of Yazd, Iran. Samples were selected simply and consecutively among 5-6 year-old children with a history of three doses of HBV vaccine in infancy. On the basis of World Health Organization’s definition on malnutrition, which considers anthropometric measurements, malnourished children entered the study. Totally 83 cases (37 boys and 46 girls) were gathered and classified into three groups of mild, moderate, and severe malnutrition. One milliliter of venous blood was taken and anti-HBs were tested by enzyme linked immunosorbant assay (ELISA). Results Overall, seroprotection rate and geometric mean titer (GMT) of anti-HBs were 60.2% and 15.47 ± 10.92 mIU/mL, respectively. Seroprotection rate was 71.4%, 55.2%, and 72.7% in mild, moderate, and severe malnourished children, respectively. GMT was 30.78 mIU/mL, 12.15 mIU/mL, and 22.95 mIU/mL in these groups, respectively. None of these two indices were significant in these groups (P = 0.471, P = 0.364). Seroprotection rate and GMT were 54.1% and 13.26 ± 11.59 mIU/mL in boys, and 65.2% and 17.5 ± 10.59 mIU/mL in girls, respectively, showing no significant relationship with gender (P = 0.302, P = 0.602). Lowest seroprotection rate was in stunted cases (47.1%) and highest in wasted children (77

Recommendations for screening, monitoring, prevention, prophylaxis and therapy of hepatitis B virus reactivation in patients with haematologic malignancies and patients who underwent haematologic stem cell transplantation-a position paper.

PubMed

Sarmati, L; Andreoni, M; Antonelli, G; Arcese, W; Bruno, R; Coppola, N; Gaeta, G B; Galli, M; Girmenia, C; Mikulska, M; Pane, F; Perno, C F; Picardi, M; Puoti, M; Rambaldi, A; Svicher, V; Taliani, G; Gentile, G

2017-12-01

-generation anti-HBV drugs be preferred to first- or second-generation antiviral drugs in the treatment of HBV reactivation with or without hepatitis flare in haematologic patients? (f) Immunization against HBV in patients with haematologic malignancies and/or patients who underwent HSCT: Should these patients be vaccinated? Which HBV vaccination schedule should be adopted? Haematologic patients should be screened for hepatitis B surface antigen (HBsAg) plus anti-hepatitis B core protein (HBc), and HBV DNA before chemotherapy. HBV DNA levels should be monitored monthly in all HBV-positive patients who do not receive prophylaxis. HBsAg-positive haematologic patients and those undergoing HSCT should receive third-generation antiviral therapy as prophylaxis. Anti-HBc-positive lymphoma patients and those receiving HSCT should receive antiviral prophylaxis. All HBV-negative haematologic patients should be vaccinated for HBV. The acquisition of data from well-designed studies is desirable in the near future. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Clinical features and predictors of outcome in acute hepatitis A and hepatitis E virus hepatitis on cirrhosis.

PubMed

Radha Krishna, Yellapu; Saraswat, Vivek Anand; Das, Khaunish; Himanshu, Goel; Yachha, Surender Kumar; Aggarwal, Rakesh; Choudhuri, Gour

2009-03-01

Acute hepatitis A and E are recognized triggers of hepatic decompensation in patients with cirrhosis, particularly from the Indian subcontinent. However, the resulting acute-on-chronic liver failure (ACLF) has not been well characterized and no large studies are available. Our study aimed to evaluate the clinical profile and predictors of 3-month mortality in patients with this distinctive form of liver failure. ACLF was diagnosed in patients with acute hepatitis A or E [abrupt rise in serum bilirubin and/or alanine aminotransferase with positive immunoglobulin M anti-hepatitis A virus (HAV)/anti-hepatitis E virus (HEV)] presenting with clinical evidence of liver failure (significant ascites and/or hepatic encephalopathy) and clinical, biochemical, endoscopic (oesophageal varices at least grade II in size), ultrasonographical (presence of nodular irregular liver with porto-systemic collaterals) or histological evidence of cirrhosis. Clinical and laboratory profile were evaluated, predictors of 3-month mortality were determined using univariate and multivariate logistic regression and a prognostic model was constructed. Receiver-operating curves were plotted to measure performance of the present prognostic model, model for end-stage liver disease (MELD) score and Child-Turcotte-Pugh (CTP) score. ACLF occurred in 121 (3.75%) of 3220 patients (mean age 36.3+/-18.0 years; M:F 85:36) with liver cirrhosis admitted from January 2000 to June 2006. It was due to HEV in 80 (61.1%), HAV in 33 (27.2%) and both in 8 (6.1%). The underlying liver cirrhosis was due to HBV (37), alcohol (17), Wilson's disease (8), HCV (5), autoimmune (6), Budd-Chiari syndrome (2), haemochromatosis (2) and was cryptogenic in the rest (42). Common presentations were jaundice (100%), ascites (78%) and hepatic encephalopathy (55%). Mean (SD) CTP score was 11.4+/-1.6 and mean MELD score was 28.6+/-9.06. Three-month mortality was 54 (44.6%). Complications seen were sepsis in 42 (31.8%), renal failure in

Payment for whole blood donations in Lithuania: the risk for infectious disease markers.

PubMed

Kalibatas, V

2008-04-01

In Lithuania, remuneration for whole blood donations still prevails, with the government covering payment for the donors. The payment per donation in cash is equal to 40 litas (euro11.6); it is offered to all blood donors and accepted by the majority of them. Donors who gave blood and received the payment are treated as remunerated donors; those who gave blood and did not take the payment are treated as non-remunerated ones. The purpose of this study was to assess the risk of payment for whole blood donations and to analyse the prevalence of infectious diseases markers per 100 remunerated and non-remunerated, first-time and regular whole blood donations, and to compare the risk ratios of infectious disease markers of remunerated and non-remunerated whole blood donations in 2005 and 2006 at the National Blood Center in Lithuania. Whole blood donors were categorized as follows: (i) first-time donor, remunerated; (ii) first-time donor, non-remunerated; (iii) regular donor, remunerated; and (iv) regular donor, non-remunerated. The blood donations were analysed for the presence or absence of the following infectious disease markers: anti-hepatitis C virus (anti-HCV), hepatitis B surface antigen (HBsAg), anti-human immunodeficiency virus (anti-HIV (1)/(2)) and syphilis. Only confirmed infectious disease markers were classified. To assess the risk of payment for whole blood donations, the prevalence of infectious disease markers per 100 donations in the different donor groups and the risk ratios between the remunerated and non-remunerated donations were determined. The prevalence per 100 first-time remunerated donations was: for anti-HCV 1.84 (2005) and 2.98 (2006); for HBsAg 1.73 (2005) and 2.03 (2006); for syphilis 0.67 (2005) and 1.03 (2006). The prevalence per 100 first-time non-remunerated donations was: for anti-HCV 0.93 (2005) and 0.98 (2006); for HBsAg 1.57 (2005) and 1.33 (2006); for syphilis 0.29 (2005) and 0.47 (2006). The first-time donors who were remunerated

Predictive factors for anti-HBs status after 1 booster dose of hepatitis B vaccine.

PubMed

Lu, I-Cheng; Jean, Mei-Chu Yen; Lin, Chi-Wei; Chen, Wei-Hung; Perng, Daw-Shyong; Lin, Chih-Wen; Chuang, Hung-Yi

2016-09-01

In Taiwan, infants need to receive 3 doses of hepatitis B virus (HBV) vaccine under the public health policy from the government. However, there are many young adults who even though received complete HBV vaccination in their childhood would lose the positive response of anti-hepatitis B surface antibody (HBs) and need the booster dose of HBV vaccine. The aim of our study is to determine the powerful predictive factor for screening the candidates who need only 1 booster dose of HB vaccine then they can regain positive postbooster anti-HBs status (≧10 mIU/mL) or protective postbooster anti-HBs status (≧100 mIU/mL).We recruited 103 university freshmen who were born after July 1986 with complete HBV vaccination in childhood, but displayed negative results for hepatitis B surface antigen and anti-HBs levels at their health examinations upon university entry. They received 1 booster dose of HB vaccine, and their anti-HBs titers were rechecked 4 weeks after the booster administration. Multivariate analysis logistic regression for positive postbooster anti-HBs status (≧10 mIU/mL, model 1) and protective postbooster anti-HBs status (≧100 mIU/mL, model 2) was done with predictive factors of prebooster anti-HBs level, body mass index, serum glutamate pyruvate transaminase level, and sex.Twenty-four students got positive postbooster anti-HBs status (10-100 mIU/mL) and 50 students got protective postbooster anti-HBs status (≧100 mIU/mL). In the model of multivariate analysis logistic regression for positive postbooster anti-HBs status (≧10 mIU/mL), prebooster anti-HBs level was the strongest predictive factor. The odds ratio was 218.645 and the P value was 0.001. Even in the model of multivariate analysis logistic regression for protective postbooster anti-HBs status (≧100 mIU/mL), prebooster anti-HBs level was still the strongest predictive factor, but the odds ratio of a protective booster effect was 2.143, with 95% confidence interval between 1

Expression of microRNA let-7a positively correlates with hepatitis B virus replication in hepatocellular carcinoma tissues

PubMed Central

Chen, Jian; Liu, Jie; Luo, Zhongguang; Jiang, Weiru; Huang, Jianping; Qiu, Zhibing; Yue, Wenjie; Wu, Lijun

2017-01-01

Let-7a miRNA is downregulated in various cancers. However, in hepatocellular carcinoma (HCC) patients infected with hepatitis B virus (HBV), the relationship between let-7a and HBV replication has not been fully elucidated. Liver specimens were collected from 23 HCC patients with chronically active HBV. The serum levels of the HBV antigens hepatitis B surface antigen (HBsAg) and hepatitis B virus e antigen (HBeAg), and the HBV antibodies, anti-HBs, anti-HBe and anti-hepatitis B core antigen (anti-HBc) were measured using the microparticle enzyme immunoassay. Let-7a levels and HBV DNA copy numbers were measured by quantitative real-time PCR (qRT-PCR) and analyzed statistically. A let-7a specific antisense oligonucleotide was introduced to the HBV-producing cell line HepG2.2.15 and a change in HBV DNA copy numbers was assessed by qRT-PCR. HCC patients with highly active HBV replication (>106 DNA copies/mL) showed higher levels of serum HBsAg and anti-HBc than patients with less active HBV replication (<103 DNA copies/mL). The level of let-7a was lower in malignant tissues than in adjacent normal tissues. However, patients with highly active HBV replication demonstrated a significantly higher level of let-7a in hepatocarcinoma tissue than patients with less active HBV replication (P < 0.05). A higher level of let-7a was observed in the HBV-producing cell line HepG2.2.15 than in HepG2 cells (P < 0.05), and let-7a down-regulation by antisense oligonucleotides led to a reduction in HBV DNA copy numbers (P < 0.05), indicating a correlation between the let-7a level and HBV replication. Down-regulation of let-7a reduces HBV replication and could prevent the development of HCC, suggesting it could be an effective therapeutic treatment for HBV infection. Impact statement Although interferon and nucleic acid analogues effectively suppress HBV replication in HBV patients, there is no treatment which eradicates the virus. Moreover, the therapeutic effect can be

Genetic polymorphisms of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 and liver cirrhosis, chronic calcific pancreatitis, diabetes mellitus, and hypertension among Japanese alcoholic men.

PubMed

Yokoyama, Akira; Mizukami, Takeshi; Matsui, Toshifumi; Yokoyama, Tetsuji; Kimura, Mitsuru; Matsushita, Sachio; Higuchi, Susumu; Maruyama, Katsuya

2013-08-01

The presence of the less-active form of alcohol dehydrogenase-1B encoded by ADH1B*1/*1 (vs. *2 allele) and active form of aldehyde dehydrogenase-2 (ALDH2) encoded by ALDH2*1/*1 (vs. *2 allele) increases the risk of alcoholism in East Asians. The subjects in this cross-sectional survey were 1,902 Japanese alcoholic men (≥40 years) who underwent ADH1B/ALDH2 genotyping. Age-adjusted daily alcohol consumption did not differ according to the ADH1B/ALDH2 genotypes. The age-adjusted odds ratios (AORs; 95% confidence interval) for liver cirrhosis (LC; n = 359, 1.58 [1.19 to 2.09]), chronic calcific pancreatitis (CP; n = 80, 2.24 [1.20 to 4.20]), and diabetes mellitus (DM; n = 383, 1.51 [1.15 to 1.99]) were higher in the ADH1B*2 allele carriers than in the ADH1B*1/*1 carriers. The AORs for LC (1.43 [1.01 to 2.02]), CP (1.68 [0.80 to 3.53]), DM (1.63 [1.15 to 2.30]), and hypertension (HT; n = 495, 1.52 [1.11 to 2.07]) were higher in the ALDH2*1/*1 carriers than in the ALDH2*1/*2 carriers. The ADH1B*2-associated AOR for LC was 2.08 (1.46 to 2.94) among those aged 40 to 59 years, but 0.89 (0.56 to 1.43) among those aged 60 years or over, and the interaction between ADH1B genotype and age on the LC risk was significant (p = 0.009). When the group with non-LC and no/mild fibrosis was used as controls, the ADH1B*2-associated AORs increased according to the severity of their liver disease: 1.67 (1.32 to 2.11) for the group with non-LC and serum type IV collagen values ≥200 ng/ml, 1.81 (1.24 to 2.63) for the group of Child-Pugh class A LC, and 3.17 (1.98 to 5.07) for the group with Child-Pugh class B/C LC. Anti-hepatitis C virus (HCV) antibody was positive in 103 patients, and the groups with a high anti-HCV antibody titer and either the ADH1B*2/*2 genotype or the ALDH2*1/*1 genotype had the highest AORs (8.83 and 4.90, respectively). The population attributable fraction (PAF) due to the ADH1B*2 allele was 29% for LC, 47% for CP, and 27% for DM, and the PAF due to the ALDH2

The warm chain.

PubMed

Bowers, J Z

1985-01-01

1 series of events carried smallpox vaccination on an eastward odyssey; a 2nd path led westward from Spain to Spanish America, to the Philippines, and to China. Francisco Xavier Balmis (1753-1819), a Spanish physician, sailed around the world in 3 years, establishing vaccination boards in South America, the Philippines, and China. He led the "Real Expedicion Martima de la Vacuna," sponsored by the Bourbon King Charles IV; its success derived from arm-to-arm passage of the virus using orphan boys on the long voyages across the Atlantic and Pacific oceans. Venezuela was the 1st country to which Balmis introduced vaccine. He divided the expedition with his deputy, Slavany, who was to lead 1 group through the Spanish colonies in the Vice-Royalty of Peru; Balmis would lead the other group across the Vice-Royalty of New Spain to the far-distant colony in the Philippines. The establishment of central boards to regulate vaccination became one of Balmis's principal preoccupations. The board he created in Venezuela served as the model for those that he and Salvany were to establish later. Balmis sailed to Havana from La Guaira on May 8, 1804; Salvany led his team to Bogota. Balmis's singular success in Caracas, and Salvany's in Bogota, where Salvany also created a Central Vaccination Board, were attributable in large measure to the total support they received from church and civil authorites. The Portuguese throne had a comparable interest in its prize colony, Brazil. In 1804, Felisberto Calderia Brant Pontes sent a group of slave children from Bahia to Lisbon so that arm-to-arm transfer could be made on the return voyage. His effort was successful, and 1335 persons had been vaccinated in Bahia by June 1, 1804. In a decree of September 3, 1803 Charles IV directed that the Balmis expedition should continue to the Philippines. The advancement of health in the Philippines was a major commitment of the Spaniards. The Philippine vaccination expedition, headed by Balmis, sailed

Aerofractures in Confined Granular Media

NASA Astrophysics Data System (ADS)

Eriksen, Fredrik K.; Turkaya, Semih; Toussaint, Renaud; Måløy, Knut J.; Flekkøy, Eirik G.

2015-04-01

processing techniques, we segment out and study the aerofractures over time looking at growth dynamics, fractal dimension and characteristics such as average finger thickness as function of depth into the solid. Also, by performing image correlation on two subsequent frames we estimate displacement fields and investigate the surrounding stress and strain fields in the solid around the fractures. Several experiments are performed with various overpressures and packing densities, and we compare the results. In a directly related project, acoustic emissions are recorded on a cell plate during experiments, and one of our goals is to correlate acoustic events and observations. We will also compare the dependence of the patterns on the saturation of the initial deformable porous material, by comparing experiments performed by air injection in air saturated granular media, to some in liquid saturated granular media. References: MJ Niebling, R Toussaint, EG Flekkøy, KJ Måløy, 2012, Dynamic aerofracture of dense granular packings, 2012, Physical Review E 86 (6), 061315 M Niebling, R Toussaint, EG Flekkøy, KJ Måløy, 2012, Numerical studies of aerofractures in porous media, Revista Cubana de Fisica 29 (1E), pp. 1E66-1E70

Effects of extracts and isolated compounds from safflower on some index of promoting blood circulation and regulating menstruation.

PubMed

Yao, Dong; Wang, Zheng; Miao, Li; Wang, Linyan

2016-09-15

Carthamus tinctorius is used as one of the Traditional Chinese Medicine (TCM) materials in prescriptions and composite to promote blood circulation to remove blood stasis, regulate menstruation and alleviate pain for over 2500 years. Modern pharmacological experiments have demonstrated that safflower has wide-reaching biological activities, including dilating coronary artery, modulating immune system, improving myocardial ischemia, anticoagulation and thromboprophylaxis, antioxidation, antihypoxic, antiaging, antifatigue, antiinflammation, anti-hepatic fibrosis, antitumor, analgesia, etc. Platelet aggregation of safflower extract and main constituents in safflower were determined by PAF-induced or ADP-induced platelet aggregation in vitro. Anticoagulation activity was measured by clotting assay of thrombin time (TT), prothrombin time (PT) and activated partial thromboplastin time (APTT) according to the methods provided by the biological reagents provider (Sun Biochemical). Antioxidant effects of safflower were assessed using DPPH radical-scavenging activity test, ABTS radical-scavenging activity test and ferric reducing antioxidant power test. In addition, rats ovary granulosa cell proliferation activity was used for the bio-activity index on regulate menstruation of safflower. Safflower extract at the concentration of 0.7g/mL (P<0.001) and 0.5g/mL (P<0.01) had significantly antagonistic effect on PAF-induced platelet aggregation, compared with negative control. And the anti-platelet aggregation of 0.7g/mL safflower extract was significantly stronger than that of positive control (P<0.001). 0.7g/mL of hydroxysafflor yellow A (P<0.01), anhydrosafflor yellow B (P<0.05), 6-hydroxykaempferol-3-O-rutinoside (P<0.05), keampferol-3-O-β-rutinoside (P<0.01) had significant effect on platelet aggregation compared with negative control. Safflower extract at the concentration of 0.5g/mL (P<0.001) and 0.125g/mL (P<0.01) could significantly inhibit ADP-induced platelet

[Tuberculin reactivity among ninth-grade schoolchildren in the city of Havana, Cuba].

PubMed

Borroto Gutiérrez, Susana M; González Ochoa, Edilberto; Armas Pérez, Luisa; Urbino López-Chávez, Amelia; Martínez, Ana Maribel; Llanes, María Josefa; Sevy Court, José; Carreras Corzo, Libertad

2003-09-01

infección tuberculosa en escolares de 14 años de Ciudad de La Habana, Cuba. Métodos. Mediante un muestreo monoetápico por conglomerados se aplicaron 1 936 pruebas de Mantoux (tuberculina) a estudiantes de noveno grado del curso escolar 1999-2000 (cohorte de los nacidos en 1985) de 20 escuelas secundarias básicas seleccionadas aleatoriamente en Ciudad de La Habana, Cuba. Las pruebas se realizaron según la técnica estándar recomendada por la Organización Mundial de la Salud y se evaluaron a las 72 horas. Se calcularon los porcentajes de reactividad y el diámetro medio de las induraciones cutáneas en la cohorte y según el sexo. Las comparaciones de medias y porcentajes se realizaron mediante la prueba de ji al cuadrado con 95% de confiabilidad. Se usó el programa Epi Info v. 6.0. Resultados. Noventa y seis por ciento de las pruebas leídas fueron negativas (0-4 mm), 2,5% fueron dudosas (5-9 mm) y 1,5% resultaron positivas ( >/= 10 mm). El porcentaje de reactividad disminuyó a 0,1% cuando se utilizó un valor de corte de 15 mm. El diámetro medio de las induraciones fue de 0,41 mm y no se detectó ninguna diferencia estadísticamente significativa en función del sexo. Conclusiones. La proporción de personas que reaccionaron a la tuberculina, usando como punto de corte un diámetro de induración cutánea de 10 mm, fue muy baja (1,5%) en este estudio y mucho más baja (0,1%) cuando se utilizó 15 mm como punto de corte. Si se toma en cuenta la baja frecuencia de tuberculosis bacilífera en Cuba y que hay una relación inversa entre el tiempo transcurrido desde la aplicación de la vacuna a base del bacilo de Calmette-Guérin (BCG) y la intensidad de la respuesta a la tuberculina, las reacciones cutáneas con un diámetro de induración >/= 10 mm podrían ser la expresión de una infección natural, por lo que, en ese caso, la prevalencia puntual de infección tuberculosa en este grupo de escolares sería de 1,5%.

China's efforts to shed its title of "Leader in liver disease".

PubMed

Li, X; Xu, W F

2007-10-01

, researchers are endeavoring to develop novel anti-hepatitis virus drugs pursuant to the "Guideline for Prevention and Treatment of Chronic Hepatitis B" enacted at the end of 2004. As Health Minister Chen Zhu said, "China must cast its title of 'Leader in liver disease' into the Pacific Ocean because," he added, "we already have an extremely effective vaccine against HBV."