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Sojan Abraham, Jang-Gi Choi, Nora M Ortega, Junli Zhang, Premlata Shankar, N Manjunath Swamy
Because endogenous interferon type I (IFN-I) produced by HIV-1 infection might complicate the analysis of therapeutically administered IFN-I, we tested different humanized mouse models for induction of IFN-I during HIV-1 infection. While HIV-1 induced high levels of IFN-α in BLT mice, IFN-I was undetectable following infection in the Hu-PBL mouse model, in which only T cells expand. We therefore tested the effect of treatment with Pegylated IFN-2 (pegasys), in Hu-PBL mice. Pegasys prevented CD4 T cell depletion and reduced the viral load for 10 days, but the effect waned thereafter...
October 6, 2016: Oncotarget
Jin Hu, Guilin Wang, Wenguo Zhao, Weiping Gao
Conjugating therapeutic proteins and peptides to poly(ethylene glycol) (PEG) can improve their pharmacokinetics and therapeutic potential. However, PEGylation suffers from non-specific conjugation, low yield and immunogenicity. Herein we report a new and general methodology to synthesize a protein-polymer conjugate with site-specificity, high yield and activity, long circulation half-life and excellent therapeutic efficacy. A phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), was grown solely from the C-terminus of interferon-alpha to form a site-specific (C-terminal) and stoichiometric (1:1) PMPC conjugate of interferon-alpha in high yield...
September 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Jin Hu, Guilin Wang, Wenguo Zhao, Xinyu Liu, Libin Zhang, Weiping Gao
Conjugating poly(ethylene glycol) (PEG), PEGylation, to therapeutic proteins is widely used as a means to improve their pharmacokinetics and therapeutic potential. One prime example is PEGylated interferon-alpha (PEGASYS). However, PEGylation usually leads to a heterogeneous mixture of positional isomers with reduced bioactivity and low yield. Herein, we report site-specific in situ growth (SIG) of a PEG-like polymer, poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA), from the C-terminus of interferon-alpha to form a site-specific (C-terminal) and stoichiometric (1:1) POEGMA conjugate of interferon-alpha in high yield...
July 2016: Biomaterials
Young Eun Chon, Dong Joon Kim, Sang Gyune Kim, In Hee Kim, Si Hyun Bae, Seong Gyu Hwang, Jeong Heo, Jeong Won Jang, Byung Seok Lee, Hyung Joon Kim, Dae Won Jun, Kang Mo Kim, Woo Jin Chung, Moon Seok Choi, Jae Young Jang, Hyung Joon Yim, Won Young Tak, Ki Tae Yoon, Jun Yong Park, Kwang-Hyub Han, Ki Tae Suk, Hyun Woong Lee, Byoung Kuk Jang, Sang Hoon Ahn
Currently, limited data are available regarding the efficacy and safety of pegylated interferon alpha-2a (PEG-IFN α-2a) in Korean patients with chronic hepatitis B (CHB), in whom hepatitis B virus (HBV) genotype C is the most common type.We collected data from 439 patients (HBeAg positive, n = 349; HBeAg negative, n = 90) with CHB who were treated with PEG-IFN α-2a as a first-line therapy from 18 institutions. Treatment responses at the end of treatment (ET) and at 6 months posttreatment (PT6) were compared between the patients who were treated for 24 weeks versus 48 weeks, and adverse events (AEs) were evaluated...
April 2016: Medicine (Baltimore)
J H C Martins, N C Santos, P Figueira, C Melo
The direct detection of reflected light from exoplanets is an excellent probe for the characterization of their atmospheres. The greatest challenge for this task is the low planet-to-star flux ratio, which even in the most favourable case is of the order of 10(-4) in the optical. This ratio decreases even more for planets in their host's habitable zone, typically lower than 10(-7). To reach the signal-to-noise level required for such detections, we propose to unleash the power of the Cross Correlation Function in combination with the collecting power of next generation observing facilities...
March 31, 2016: Origins of Life and Evolution of the Biosphere
Edouard Alphandéry, Pierre Grand-Dewyse, Raphael Lefèvre, Chalani Mandawala, Mickael Durand-Dubief
Several nanoformulated anti-cancer substances are currently commercialized or under development. Pre-clinical and clinical results have revealed better properties, that is, larger efficacy and lower toxicity for these substances than for conventional anti-cancer treatments. Here, we review the development of several of these substances such as Marqibo, Myocet, Doxil, DaunoXome, MM398, MM302, Mepact, Versamune, Thermodox, Depocyt, Livatag, Abraxane, Eligard, Opaxio, Zinostatin Stimalamer (SMANCS), Pegasys and PegIntron, BIND-014, CRLX-101, Oncaspar, Neulasta, Aurimmune, Auroshell, AuNPs, Nanotherm, NanoXray, Magnetosome chains, Kadcyla (T-DM1), Ontak (DAB/IL2), Gendicine and Curcumin...
2015: Expert Review of Anticancer Therapy
Jan Jacques Michiels
Prospective studies indicate that the risk of microvascular and major thrombosis in untreated thrombocythemia in various myeloproliferative neoplasms (MPN-T) is not age dependent and causally related to platelet-mediated thrombosis in early, intermediate and advanced stages of thrombocythemia in MPN-T. If left untreated both microvascular and major thrombosis frequently do occur in MPN-T, but can easily be cured and prevented by low dose aspirin as platelet counts are above 350 × 10(9)/L. The thrombotic risk stratification in the retrospective Bergamo study has been performed in 100 essential thrombocythemia (ET) patients not treated with aspirin thereby overlooking the discovery in 1985 of aspirin responsive platelet-mediated arteriolar and arterial thrombotic tendency in MPN-T disease of ET and polycythemia vera (PV) patients...
August 4, 2015: World Journal of Critical Care Medicine
Dalia El Sabaawy, Sahar El-Haggar, Hoda El-Bahrawy, Imam Waked, Hala El-Said
HCV infection presents a vast burden in the regions of high prevalence such as Egypt, where most HCV isolates are genotype 4b. Combined treatment of three variants of pegylated interferon and ribavirin is still the standard of care in Egypt. However, no conclusive data confirming their efficacy are available. Here, 60 chronic HCV patients were randomized for ribavirin plus Peg Intron (PEG-IFNα-2b), Pegasys (PEG-IFNα-2a) or Reiveron Retard (PEG-IFNα-2a). Serum interferon and antibody (Ab) levels were measured, and responses and costs were compared...
June 2015: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
Nadeem Javaid, Mohsin Raza Jafri, Zahoor Ali Khan, Nabil Alrajeh, Muhammad Imran, Athanasios Vasilakos
Appropriate network design is very significant for Underwater Wireless Sensor Networks (UWSNs). Application-oriented UWSNs are planned to achieve certain objectives. Therefore, there is always a demand for efficient data routing schemes, which can fulfill certain requirements of application-oriented UWSNs. These networks can be of any shape, i.e., rectangular, cylindrical or square. In this paper, we propose chain-based routing schemes for application-oriented cylindrical networks and also formulate mathematical models to find a global optimum path for data transmission...
2015: Sensors
B Podobnik, B Helk, V Smilović, Š Škrajnar, K Fidler, S Jevševar, A Godwin, P Williams
The covalent attachment of poly(ethylene glycol) (PEG) to therapeutic proteins is a commonly used approach for extending in vivo half-lives. A potential limitation of this PEGylation strategy is the adverse effect of PEG on conjugate viscosity. Interferon-alpha (IFN) was conjugated via its N-terminal amino group by reductive amination to α-aldehyde functional comb-shaped PolyPEG polymers (50 and 70 kDa) and to linear PEG (30 kDa). In vitro potencies of the purified PEGylated IFN conjugates were measured by reporter gene assay using a HEK293P/ISRE-SEAP cell line...
March 18, 2015: Bioconjugate Chemistry
Olga Khokhlova, Ara Reizis, Lidya Serebrovskaya, Natalia Gerasimova, Vadim Pokrovskiy
INTRODUCTION: Depletion of cellular pool and constant activation of plasmacytoid dendritic cells (pDCs) in HIV-infected persons (HIV+) are associated with disease progression and manifestation of opportunistic infections. The influence of highly-active antiretroviral treatment (HAART) and suppressed HCV-co-infection (HIV+/HCV+) on the extent of these changes remains unknown. OBJECTIVE: To study parameters of pDCs in peripheral blood of HIV+ and HIV+/HCV+ patients on HAART...
2014: Journal of the International AIDS Society
Debbie Hartwell, Keith Cooper, Geoff K Frampton, Louise Baxter, Emma Loveman
BACKGROUND: Optimal therapy for children with chronic hepatitis C is unclear. Two treatment regimens are currently licensed in children. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of peginterferon alfa-2a (Pegasys®, Roche) and peginterferon alfa-2b [ViraferonPeg®, Merck Sharp & Dohme (MSD)] in combination with ribavirin (RBV), within their licensed indications, for the treatment of chronic hepatitis C virus (HCV) in children and young people aged 3-17 years...
October 2014: Health Technology Assessment: HTA
Bo Zhang, Mintao Hu, Lihua Huang, Yunchuan Pu, Hao Pei, Zhong Hua, Shangzhi Yao
The aim of the present study was to observe the effects of Fuzheng Huayu capsule combined with Pegasys (peginterferon α-2a) on hepatic fibrosis in rats and in the treatment of patients with genotype 1 hepatitis C and hepatic cirrhosis. A dimethylnitrosamine (DMN)-induced rat model of liver injury was established. Fuzheng Huayu capsule combined with Pegasys was administered to the rats and the DMN-induced hepatocyte apoptosis was observed. In addition, a total of 100 patients with genotype 1 hepatitis C and hepatic cirrhosis were treated by oral administration of Fuzheng Huayu capsule combined with Pegasys or with Pegasys alone...
October 2014: Experimental and Therapeutic Medicine
Xuefu Chen, Xiaoping Chen, Wenli Chen, Xiaojun Ma, Jing Huang, Ren Chen
The present study compared the efficacy of standard and extended durations of PEG-IFNα-2a monotherapy for treatment of HBeAg-negative Chinese patients with chronic hepatitis B. Patients were randomized to receive standard therapy (n = 38; 48 weeks treatment) or extended therapy (n = 42; 72 weeks treatment). Extended therapy resulted in a significantly higher HBV DNA inhibition at 24 and 48 weeks after the end of treatment, a significantly higher sustained HBV DNA inhibition at the end of treatment, and a significantly lower HBsAg level at 24 and 48 weeks after the end of treatment (P < 0...
October 2014: Journal of Medical Virology
Mohsen Vahedi, Asma Pourhoseingholi, Sara Ashtari, Mohamad Amin Pourhoseingholi, Maryam Karkhane, Bijan Moghimi-Dehkordi, Azadeh Safaee, Zahra Kimia, Seyed Moayed Alavian
AIM: This study compared PR and NB in predicting HCV patient costs. The objective of this study was to predict the direct cost of the HCV patient in Iran. BACKGROUND: Hepatitis C virus (HCV) is a common and expensive infectious disease in Iran. Cost associated with HCV and its complications has not been well characterized. Analysis of cost data is important in providing consistent information to aid budgeting decisions and certain statistical regression models need for prediction mean costs...
2012: Gastroenterology and Hepatology From Bed to Bench
Yung-Kuei Chiang, Neng-Chung Wang, Chih-Hung Hsieh
In a wireless sensor network (WSN), a great number of sensor nodes are deployed to gather sensed data. These sensor nodes are typically powered by batteries so their energy is restricted. Sensor nodes mainly consume energy consumption in data transmission, especially for a long distance. Since the location of the base station (BS) is remote, the energy consumed by each node to directly transmit its data to the BS is considerable and the node will die very soon. A well-designed routing protocol is thus essential to reduce the energy consumption...
2014: Sensors
Tai-Chung Tseng, Jia-Horng Kao, Ding-Shinn Chen
INTRODUCTION: Hepatitis B virus (HBV) infection is a global health problem. Peginterferon α (PEG-IFN), which includes PEG-IFN α-2a (Pegasys) and PEG-IFN α-2b (Peg-Intron), can be used to treat patients with chronic hepatitis B (CHB) infection. A finite duration of PEG-IFN therapy may lead to long-term viral suppression. Clinically, it is important to identify super-responders and null-responders to PEG-IFN due to its substantial side effects. AREAS COVERED: From the literature review, it is known that PEG-IFN is more effective for hepatitis B e antigen (HBeAg)-positive patients who have high pre-treatment alanine aminotransferase level, lower HBV DNA level and genotype A (vs genotype D), as well as those with more favourable viral predictors, such as precore stop codon or basal core promoter mutants infections in Asian patients and wild-type virus in Caucasian patients...
July 2014: Expert Opinion on Biological Therapy
Yun-Song Qian, Ling Li
OBJECTIVE: To observe the therapeutic effects of Pegasys (pegylated interferon alpha-2a) in chronic hepatitis B (CHB) patients with low-level alanine transaminase (ALT) < 2 x upper limit of normal (ULN). METHODS: One hundred and seven CHB patients were randomized enrolled including 52 with ALT < 2 x ULN and liver tissues inflammation activity > or = G2 as observational group and 55 with ALT > 2 x ULN as control group. All the enrolled patients received pegasys treatment for 48 weeks and the responses between two groups were compared...
June 2013: Chinese Journal of Experimental and Clinical Virology
Stuart K Roberts, Joanne Mitchell, Reynold Leung, David Booth, Steven Bollipo, George Ostapowicz, Andrew Sloss, Geoffrey W McCaughan, Gregory J Dore, Alexander Thompson, Darrell Hg Crawford, William Sievert, Martin Weltman, Wendy Cheng, Jacob George
BACKGROUND AND AIMS: The aim of this study was to examine the distribution of interferon lambda-3 (IFN-λ3) gene polymorphisms in previously untreated Australian patients with genotype 1 (Gt1) chronic hepatitis C (CHC) and to compare the IFN-λ3 genotype frequency among the different ethnic populations. METHODS: This was a prospective, multicenter, observational study undertaken by the Australian Liver Association Clinical Research Network. Eligible subjects had Gt1 CHC and were being considered for and/or undergoing treatment...
January 2014: Journal of Gastroenterology and Hepatology
Anthony T Tan, Long Truong Hoang, Daniel Chin, Erik Rasmussen, Uri Lopatin, Stefan Hart, Hans Bitter, Tom Chu, Lore Gruenbaum, Palani Ravindran, Hua Zhong, Ed Gane, Seng Gee Lim, Wan Cheng Chow, Pei-Jer Chen, Rosemary Petric, Antonio Bertoletti, Martin Lloyd Hibberd
BACKGROUND & AIMS: The interaction between HBV replication and immune modulatory effects mediated by IFNα therapy is not well understood. We characterized the impact of HBV DNA replication on the early IFNα-induced immunomodulatory mechanisms. METHODS: We interrogated the transcriptional, serum cytokine/chemokine and cellular immune profiles of 28 patients with HBeAg+ chronic HBV infection (CHB) randomly assigned to one of 4 treatment cohorts (untreated n=5, weekly dosing of 360 μg Pegasys [PegIFNα] n=11, daily dose of 300 mg Viread [tenofovir disoproxil fumarate, TDF] n=6, or a combination of both n=6)...
January 2014: Journal of Hepatology
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