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Virological response and resistance mutations to NS3/4A inhibitors in hepatitis c virus-human immunodeficiency virus coinfection

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World Journal of Hepatology 2015年第18期7卷 2177-2183页

作者： Alissa Naqvi Valérie Giordanengo Brigitte Dunais Francine de Salvador-Guillouet Isabelle Perbost Jacques Durant Pascal Pugliese Aline Joulié Pierre Marie Roger Eric Rosenthal Infectious Diseases Department Archet Hospital Centre Hospitalier Universitaire Virology Laboratory Archet Hospital Centre Hospitalier Universitaire Internal Medicine Department Archet Hospital Centre Hospitalier Universitaire

AIM: To evaluate virological response to telaprevir or boceprevir in combination with pegylated interferon and ribavirin and resistance mutations to NS3/4A inhibitors in hepatitis c virus-human immunodeficiency virus(HcV-HIV) coinfected patients in a real life setting. METHODS: Patients with HcV genotype 1-HIV coinfection followed in Nice University Hospital internal medicine and infectious diseases departments who initiated treatment including pegylated interferon and ribavirin(Peg IFN/RBV) + telaprevir or boceprevir, according to standard treatment protocols, between August 2011 and October 2013 entered this observational study. Patient data were extracted from an electronic database(Nadis®). Liver fibrosis was measured by elastometry(Fibroscan®) with the following cut-off values: F0-F1: < 7.1 k Pa, F2: 7.1-9.5 k Pa, F3: 9.5-14.5 k Pa, F4: ≥ 14.5 k Pa. The proportion of patients with sustained virological response(SVR) twelve weeks after completing treatment, frequency and type of adverse events, and NS3/4A protease inhibitor mutations were described. RESULTS: Forty-one patients were included: 13(31.7%) patients were HcV-treatment na?ve, 22(53.7%) had advanced liver fibrosis or cirrhosis(Fibroscan stage F3 and F4); none had decompensated cirrhosis or hepatocellular carcinoma; all were receiving antiretroviral treatment, consisting for most them(83%) in either a nucleoside reverse-transcriptase inhibitor/protease inhibitor or/integrase inhibitor combination; all patients had undetectable HIV-RNA. One patient was lost to follow-up. SVR was achieved by 52.5% of patients. Five patients experienced virological failure during treatment and four relapsed. Seven discontinued treatment due to adverse events. Main adverse events included severe anemia(88%) and rash(25%). NS3/4A protease mutations were analyzed at baseline and at the time of virological failure in the 9 patients experiencing non-response, breakthrough or relapse. No baseline resistance mutation cou

关键词： Telaprevir Boceprevir Hepatitis c virushuman immun

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Programmed death-1/programmed death-L1 signaling pathway and its blockade in hepatitis c virus immunotherapy

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World Journal of Hepatology 2015年第23期7卷 2449-2458页

作者： Mohamed L Salem Ahmed El-Badawy Center of Excellence in Cancer Research Tanta University Immunology and Biotechnology Division Zoology Department Faculty of Science Center of Excellence for Stem Cells and Regenerative Medicine Zewail City of Science and Technology

chronic hepatitis c virus(HcV) infection is a public health issue that often progresses to life-threatening complications, including liver cirrhosis, fibrosis, and hepatocellular carcinoma. Impaired immune responses to HcV are key features of chronic HcV infection. Therefore, intervention strategies usually involve enhancing the immune responses against HcV. cytotoxic cD8+ T lymphocytes(cTLs) play a critical role in the control of HcV infection. However, their cytolytic function can be impaired by the expression of co-inhibitory molecules. Programmed death-1(PD-1) receptor and its ligand PD-L1 function in a T cell co-inhibitory pathway, which either blocks the function of cTLs or the differentiation of cD8+ T cells. During chronic HcV infection, the immune inhibitory receptor PD-1 is upregulated on dysfunctional HcV-specific cD8+ T cells. As such, blockade of the PD-1/PD-L1 pathway in these cD8+ T cells might restore their functional capabilities. Indeed, clinical trials using therapies to block this pathway have shown promise in the fostering of anti-HcV immunity. Understanding how chronic HcV infection induces upregulation of PD-1 on HcV specific T cells and how the PD-1/PD-L1 interaction develops HcV specific T cell dysfunction will accelerate the development of an efficacious prophylactic and therapeutic vaccination against chronic HcV infections, which will significantly improve HcV treatments and patient survival. In this review, we discuss the relationship between PD-1 expression and clinical responses and the potential use of PD-1 blockade for anti-HcV therapy.

关键词： Hepatitis c virus Programmed death-1 Hepatitis c v

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Methodology to assess distribution transformer thermal capacity for uptake of low carbon technologies

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IET GENERATION TRANSMISSION & DISTRIBUTION 2017年第7期11卷 1645-1651页

作者： Gao, Yuan Patel, Beval Liu, Qiang Wang, Zhongdong Bryson, Geraldine Univ Manchester Sch Elect & Elect Engn Manchester M13 9PL Lancs England Elect North West Ltd 304 Bridgewater PlBirchwood Pk Warrington WA3 6XG Cheshire England

Low-voltage network is concerned on the penetration of low carbon technologies. Distribution transformer thermal capacity is one of the most concerned, due to the aged and capital-intensive nature of the transformer fleet. Extensive studies have been done on this topic, and most of them have applied exiting thermal models such as IEc 60076 thermal model to estimate the hot-spot temperature (HST). However, it is lack of consideration on how accurate the thermal model is or how to refine the thermal model for more accurate estimation of HST. In this study, a methodology is introduced to improve the accuracy of IEc thermal model by refining its thermal parameters based on measured temperature data during the heat run test. Verification of the methodology under one 1 MVA 6.6/0.415 kV distribution transformer shows that the accuracy of predicting the HST is improved by reducing the maximum error from 25.8 to 3.6 K under constant loads and 8.15 to 4.16 K under cyclic loads. Also, a worst-case scenario study under the penetration of electric vehicles (EVs) shows the maximum penetration level of EVs is improved by 9% by applying refined thermal parameters to estimate the HST of the distribution transformer.

关键词： power transformers distribution networks carbon thermal analysis distribution transformer thermal capacity assessment low carbon technology low-voltage network thermal models hot-spot temperature estimation IEc 60076 thermal model HST temperature data heat run test HST prediction electric vehicle penetration EVs apparent power 1 MVA voltage 6.6 kV voltage 0.415 kV temperature 8.15 K to 4.16 K c

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Limitation in growth temperature for water-assisted single wall carbon nanotube forest synthesis

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MRS ADVANcES 2018年第1-2期3卷 91-96页

作者： Sakurai, Shunsuko Yamada, Ivfaho Hata, Kenji Futaba, Don N. Natl Inst Adv Ind Sci & Technol CNT Applicat Res Ctr Cent 51-1-1 Higashi Tsukuba Ibaraki 3058565 Japan

In this study, we examined the limitations in growth temperatures for single-walled carbon nanotube (SWNT) forest synthesis using a water (H2O) growth enhancer as highlighted by a dramatic decrease in growth efficiency at high temperatures. comparative synthesis using a carbon monoxide (cO) growth enhancer demonstrated a wider temperature window for SWNT forest synthesis. We found that SWNT forests taller than 100 m could not been synthesized above 850 degrees c by using H2O, but by using cO, tall (>800 mu m) forests could be synthesized at growth temperatures exceeding 900 degrees c. The dependency of H2O concentration showed that H2O, itself, was the cause for the reduced growth efficiency observed at higher temperatures. In contrast, increased cO concentrations did not result in any drop in the carbon nanotube (cNT) yield across the entire temperature range. While a severe drop of cNT yield above 950 degrees c was observed when cO was used, the origin was found to stem from catalyst particle aggregation enhanced by diffusion on the surface rather than cO itself. Therefore, the ability to synthesize at higher growth temperatures is advantageous when using more stable carbon feedstocks, such as methane.

关键词： c chemical vapor deposition (cVD) (chemical reaction) catalytic

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Hepatocellular carcinoma: Known and Emerging Risk Factors

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Journal of cancer Therapy 2018年第5期9卷 417-437页

作者： Daniela Sciancalepore Maria Teresa Zingaro chiara Valentina Luglio carlo Sabbà Nicola Napoli Clinica Medica &quot Cesare Frugoni&quot Department of Interdisciplinary Medicine University of Bari &quot Aldo Moro&quot Bari Italy

Hepatocellular carcinoma (Hcc) is the most frequent primary liver cancer with a high mortality rate. While chronic hepatitis B virus (HBV) and hepatitis c virus (HcV) infections represent the leading risk factors worldwide, the spreading of metabolic disorders, such as diabetes, obesity and non-alcoholic fatty liver disease (NAFLD) justifies the increasing attention on their oncogenic mechanisms. This review discusses about the main pathogenic mechanisms implicated in occurrence of Hcc in presence of viral and metabolic diseases. Additionally, it points to the importance of clinical surveillance for those patients considered at risk of Hcc and highlights the strategical role of serum markers, such as alfa-fetoprotein (αFP) and Protein Induced by Vitamin K Absence or Antagonist II (PIVKA-II), which, in association to a strictly instrumental follow-up, contribute to the early detection of hepatic nodules with a better prognosis for affected patients.

关键词： Hepatocellular carcinoma (Hcc) Hepatitis B Virus (HBV) Hepatitis c Virus (HcV) Non-Alcoholic Fatty Liver Disease (NAFLD) Non-Alcoholic Steatohepatitis (NASH) Insulin Resistance (IR) Type 2 Diabetes Mellitus (T2DM) Intestinal Microbiota Visceral Obesity Alfa-Fetoprotein (αFP) Protein Induced by Vitamin K Absence or Antagonist II (PIVKA-II)

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Evidence-based consensus on the diagnosis, prevention and management of hepatitis c virus disease

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World Journal of Hepatology 2015年第3期7卷 616-627页

作者： Mahrukh Akbar Shaheen Muhammad Idrees Division of Molecular Virology National Centre of Excellence in Molecular Biology University of the Punjab

Hepatitis c virus(HcV) is a potent human pathogen and is one of the main causes of chronic hepatitis round the world. The present review describes the evidencebased consensus on the diagnosis, prevention and management of HcV disease. Various techniques, for the detection of anti-HcV immunoglobulin G immunoassays, detection of HcV RNA by identifying virus-specific molecules nucleic acid testings, recognition of core antigen for diagnosis of HcV, quantitative antigenassay, have been used to detect HcV RNA and core antigen. Advanced technologies such as nanoparticlebased diagnostic assays, loop-mediated isothermal amplification and aptamers and Ortho trak-c assay have also come to the front that provides best detection results with greater ease and specificity for detection of HcV. It is of immense importance to prevent this infection especially among the sexual partners, injecting drug users, mother-to-infant transmission of HcV, household contact, healthcare workers and people who get tattoos and piercing on their skin. Management of this infection is intended to eradicate it out of the body of patients. Management includes examining the treatment(efficacy and protection), assessment of hepatic condition before commencing therapy, controlling the parameters upon which dual and triple therapies work, monitoring the body after treatment and adjusting the co-factors. Examining the treatment in some special groups of people(HIV/HcV co-infected, hemodialysis patients, renal transplanted patients).

关键词： Hepatitis c virus Enzyme immunoassay Nucleic acid testing Loop-mediated isothermal amplification Sustained viral response Telaprevir Boceprevir Liver transplant

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Monoclonal antibodies:Principles and applications of immmunodiagnosis and immunotherapy for hepatitis c virus

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World Journal of Hepatology 2015年第22期7卷 2369-2383页

作者： Ashraf Tabll Aymn T Abbas Sherif El-Kafrawy Ahmed Wahid Microbial Biotechnology Department (Biomedical Technology Group) Genetic Engineering and Biotechnology DivisionNational Research Centre Biotechnology Research Laboratories Gastro--eneterology Surgery CentreMansoura University Special Infectious Agents Unit King Fahd Medical Research CenterKing Abdulaziz University National Liver Institute Menoufia University Biochemistry Department Molecular and Cellular Biology UnitFaculty of PharmacyMinia University

Hepatitis c virus(HcV) is a major health problem worldwide. Early detection of the infection will help better management of the infected cases. The monoclonal antibodies(m Ab) of mice are predominantly used for the immunodiagnosis of several viral,bacterial,and parasitic antigens. Serological detection of HcV antigens and antibodies provide simple and rapid methods of detection but lack sensitivity specially in the window phase between the infection and antibody development. Human mA b are used in the immunotherapy of several blood malignancies,such as lymphoma and leukemia,as well as for autoimmune diseases. In this review article,we will discuss methods of mouse and human monoclonal antibody production. We will demonstrate the role of mouse mA b in the detection of HcV antigens as rapid and sensitive immunodiagnostic assays for the detection of HcV,which is a major health problem throughout the world,particularly in Egypt. We will discuss the value of HcV-neutralizing antibodies and their roles in the immunotherapy of HcV infections and in HcV vaccine development. We will also discuss the different mechanisms by which the virus escape the effect of neutralizing mA b. Finally,we will discuss available and new trends to produce antibodies,such as egg yolk-based antibodies(Ig Y),production in transgenic plants,and the synthetic antibody mimics approach.

关键词： Hepatitis c virus Monoclonal antibodies Immunodiag

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Ribavirin contributes to eradicate hepatitis c virus through polarization of T helper 1/2 cell balance into T helper 1 dominance

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World Journal of Hepatology 2015年第25期7卷 2590-2596页

作者： Katsuhisa Nakatsuka Masanori Atsukawa Masumi Shimizu Hidemi Takahashi chiaki Kawamoto Division of Gastroenterology and Hepatology Department of Internal MedicineNippon Medical School Microbiology and Immunology Nippon Medical School

The mechanism of action of ribavirin(RBV) as an immunomodulatory and antiviral agent and its clinical significance in the future treatment of patients with hepatitis c virus(HcV) infection are *** up-regulates type 1 and/or 2 cytokines to modulate the T helper(Th) 1/2 cell balance to Th1 *** of co-stimulatory signaling indicated that RBV down-modulates inducible co-stimulator on Th cells,which contributes to differentiating na?ve Th cells into Th2 cells while reducing their interleukin-10 *** effects on T-regulatory(Treg) cells were also investigated,and RBV inhibited the differentiation of na?ve Th cells into adaptive Treg cells by downmodulating forkhead *** findings indicate that RBV mainly down-regulates the activity of Th2 cells,resulting in the maintenance of Th1 activity that contributes to abrogating HcV-infected *** an interferon-free treatment regimen exhibits almost the same efficacy without serious complications,regimens with RBV will be still be used because of their ability to facilitate the cellular immune response,which may contribute to reducing the development of hepatocellular carcinogenesis in patients infected with HcV.

关键词： Ribavirin Forkhead box-P3 T helper 1/2cell balance T-regulatory lymphocytes Inducible costimulator Interleukin-10 Hepatitis c virus infection

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A Potential Use γ-Al 2 O 3 coated cordierite Honeycomb Reinforced Ti 0.97 Pd 0.03 O 2−δ catalyst for Selective High Rates in coupling reactions

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Materials Today: Proceedings 2018年第10期5卷 22466-22472页

作者： G.O. Obaiah K.H. Shivaprasad M. Mylarappa K. Srikanth bhat Department of chemistry Vijayanagara Sri Krishna Devaraya University Ballary 583104 Karnataka India Research centre Talent development centre IISC Kudhapur Chitradurga 577501 Karnataka India Research Centre Department of Chemistry AMC Engineering College Bannerghatta Road Bangaluru-560083 Karnataka India Department of Studies and Research in Chemistry Tumkur University B.H Road Tumkur Karnataka India

The current work was mainly focused on a potential use of γ-Al 2 O 3 coated cordierite honeycomb reinforced Ti 0.97 Pd 0.03 O 2 catalyst for selective high rates in coupling reactions. The Titanium isopropoxide {Ti (Oc 3 H 7 ) 4 }, Pdcl 2 and glycine are the precursors used for the synthesis of Ti 0.97 Pd 0.03 O 2−δ . In typical coating of (3 % atom Pd on TiO 2 ), 9.7 mmol of TiO(NO 3 ) 2 solution, 0.3 mmol Pdcl 2 and 11 mmol glycine were dissolved to make a solution. The obtained sample of the monolith before and after coating and catalytic activity were studied by using PXRD, IR, and Mass spectroscopy. TEM and SEM. The surface image of the catalyst coated monolith was characterized by FEI Quanta scanning electron microscope. In the coupling reactions have been investigated in view of their potential use in the industrial passive autocatalytic recombines (PAR). The recombination reaction of hydrogen and oxygen has been monitored using Ti 0.97 Pd 0.03 O 2−δ catalyst

关键词： Ti (Oc 3 H 7 ) 4 Pdcl 2 c 2 H 5 NO 2 γ-Al 2 O 3 ceramic cordierite coated honeycomb coupling reactions catalytic applications

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Hepatitis c in hemodialysis patients

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World Journal of Hepatology 2015年第3期7卷 548-558页

作者： Smaragdi Marinaki John N Boletis Stratigoula Sakellariou Ioanna K Delladetsima Department of Nephrology and Renal Transplantation Unit Medical School University of Athens Laiko General Hospital First Department of Pathology Medical School University of Athens

Despite reduction of hepatitis c prevalence after recognition of the virus and testing of blood products, hemodialysis(HD) patients still comprise a high risk group. The natural history of hepatitis c virus(HcV) infection in dialysis is not fully understood while the clinical outcome differs from that of the general population. HD patients show a milder liver disease with lower aminotransferase and viral levels depicted bymilder histological features on liver biopsy. Furthermore, the "silent" clinical course is consistent with a slower disease progression and a lower frequency of cirrhosis and hepatocellular carcinoma. Potential explanations for the "beneficial" impact of uremia and hemodialysis on chronic HcV infection are impaired immunosurveillance leading to a less aggressive host response to the virus and intradialytic release of "hepatoprotective" cytokines such as interferon(IFN)-α and hepatocyte growth factor. However, chronic hepatitis c is associated with a higher liver disease related cardiovascular and allcause mortality of HD patients. Therapy is indicated in selected patients groups including younger patients with low comorbidity burden and especially renal transplant candidates, preferably after performance of a liver biopsy. According to current recommendations, choice of treatment is IFN or pegylated interferon with a reported sustained viral response at 30%-40% and a withdrawal rate ranging from 17% to 30%. New data regarding combination therapy with low doses of ribavirin which provide higher standard variable rates and good safety results, offer another therapeutic option. The new protease inhibitors may be the future for HcV infected HD patients, though data are still lacking.

关键词： Hemodialysis Hepatitis c infection Interferon Ribavirin Protease inhibitors

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