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https://www.readbyqxmd.com/read/28731677/an-evaluation-of-optimal-pegylation-strategies-for-maximizing-the-lymphatic-exposure-and-antiviral-activity-of-interferon-after-subcutaneous-administration
#1
Linda J Chan, Orlagh M Feeney, Nathania J Leong, Victoria M Mcleod, Christopher J H Porter, Charlotte C Williams, Lisa M Kaminskas
Interferon α2 is an antiviral/antiproliferative protein that is currently used to treat hepatitis C infections and several forms of cancer. Two PEGylated variants of interferon α2 (containing 12 and 40 kDa PEGs) are currently marketed and display longer plasma circulation times than unmodified interferon. With increasing realization that the lymphatic system plays an important role in the extrahepatic replication of the hepatitis C virus and in the metastatic dissemination of cancers, this study sought to evaluate PEGylation strategies to optimally enhance the antiviral activity and plasma and lymphatic exposure of interferon after subcutaneous administration in rats...
July 21, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28728000/tailor-made-purified-human-platelet-lysate-concentrated-in-neurotrophins-for-treatment-of-parkinson-s-disease
#2
Ming-Li Chou, Joe-Wei Wu, Flore Gouel, Aurélie Jonneaux, Kelly Tillerman, Ting-Yi Renn, Charlotte Laloux, Hung-Ming Chang, Liang-Tzung Lin, Jean-Christophe Devedjian, David Devos, Thierry Burnouf
Human platelet lysates (PLs), which contain multiple neurotrophins, have been proposed for treating neurodegenerative disorders, including Parkinson's disease (PD). However, current PLs suspended in plasma have high protein content and contain fibrinogen/fibrin and, following activation, also proteolytic and thrombogenic enzymes. Upon brain administration, such PLs may saturate the cerebrospinal fluid and exert neurotoxicity. We assessed whether purified PLs, concentrated in neurotrophins, protected dopaminergic neurons in PD models...
July 12, 2017: Biomaterials
https://www.readbyqxmd.com/read/28726043/injection-drug-use-unemployment-and-severe-food-insecurity-among-hiv-hcv-co-infected-individuals-a-mediation-analysis
#3
Taylor McLinden, Erica E M Moodie, Anne-Marie Hamelin, Sam Harper, Sharon L Walmsley, Gilles Paradis, Wusiman Aibibula, Marina B Klein, Joseph Cox
Severe food insecurity (FI), which indicates reduced food intake, is common among HIV-hepatitis C virus (HCV) co-infected individuals. Given the importance of unemployment as a proximal risk factor for FI, this mediation analysis examines a potential mechanism through which injection drug use (IDU) is associated with severe FI. We used biannual data from the Canadian Co-infection Cohort (N = 429 with 3 study visits, 2012-2015). IDU in the past 6 months (exposure) and current unemployment (mediator) were self-reported...
July 19, 2017: AIDS and Behavior
https://www.readbyqxmd.com/read/28722244/risk-of-liver-decompensation-with-cumulative-use-of-mitochondrial-toxic-nucleoside-analogues-in-hiv-hepatitis-c-virus-coinfection
#4
Vincent Lo Re Rd, Bret Zeldow, Michael J Kallan, Janet P Tate, Dena M Carbonari, Sean Hennessy, Jay R Kostman, Joseph K Lim, Matthew Bidwell Goetz, Robert Gross, Amy C Justice, Jason A Roy
PURPOSE: Among patients dually infected with human immunodeficiency virus (HIV) and chronic hepatitis C virus (HCV), use of antiretroviral therapy (ART) containing mitochondrial toxic nucleoside reverse transcriptase inhibitors (mtNRTIs) might induce chronic hepatic injury, which could accelerate HCV-associated liver fibrosis and increase the risk of hepatic decompensation and death. METHODS: We conducted a cohort study among 1747 HIV/HCV patients initiating NRTI-containing ART within the Veterans Aging Cohort Study (2002-2009) to determine if cumulative mtNRTI use increased the risk of hepatic decompensation and death among HIV-/HCV-coinfected patients...
July 19, 2017: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/28713943/astragaloside-iv-downregulates-the-expression-of-mdr1-in-bel%C3%A2-7402-fu-human-hepatic-cancer-cells-by-inhibiting-the-jnk-c%C3%A2-jun-ap%C3%A2-1-signaling-pathway
#5
Pei-Pei Wang, Jia-Jie Luan, Wen-Ke Xu, Lin Wang, Du-Juan Xu, Chun-Yan Yang, Yan-Hong Zhu, Ya-Qin Wang
Previous studies demonstrated that astragaloside IV (ASIV) is a potential P‑glycoprotein (P‑gp)‑mediated multidrug resistance (MDR) reversal agent through mechanisms involving downregulation of the gene expression of mdr1. In order to investigate whether the c‑Jun N‑terminal kinase (JNK) signaling pathway is involved in the mechanism underlying ASIV‑induced downregulated the expression of mdr1, the present study used 5‑fluorouracil‑resistant Bel‑7402/FU human hepatic cancer cells as target cells...
July 5, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28708100/airborne-pm2-5-induced-hepatic-insulin-resistance-by-nrf2-jnk-mediated-signaling-pathway
#6
Jinxia Xu, Wei Zhang, Zhongbing Lu, Fang Zhang, Wenjun Ding
Animal and epidemiological studies have suggested that exposure to airborne particulate matter (PM) with an aerodynamic diameter less than 2.5 μm (PM2.5) is associated with the risk of developing type 2 diabetes. However, the mechanism underlying this risk is poorly understood. In the present study, we investigated the effects of PM2.5 exposure on glucose homeostasis and related signaling pathways in mice. Wild-type and nuclear factor erythroid 2-related factor 2 (Nrf2) knockout (Nrf2(-)(/)(-)) C57BL/6 male mice were exposed to either ambient concentrated PM2...
July 14, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28707373/biomarker-responses-and-pah-ratios-in-fish-inhabiting-an-estuarine-urban-waterway
#7
Rafael Mendonça Duarte, Helen Sadauskas-Henrique, Vera Maria Fonseca de Almeida-Val, Adalberto Luis Val, Helen Elizabeth Nice, Marthe Monique Gagnon
Many cities worldwide are established adjacent to estuaries and their catchments resulting in estuarine contamination due to intense anthropogenic activities. The aim of this study was to evaluate if fish living in an estuarine urban waterway were affected by contamination, via the measurement of a suite of biomarkers of fish health. Black bream (Acanthopagrus butcheri) were sampled in a small urban embayment and a suite of biomarkers of fish health measured. These were condition factor (CF), liver somatic index (LSI), gonadosomatic index (GSI), hepatic EROD activity, polycyclic aromatic hydrocarbon (PAH) biliary metabolites, serum sorbitol dehydrogenase (s-SDH) and branchial enzymes cytochrome C oxidase (CCO), and lactate dehydrogenase (LDH) activities...
July 14, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28705429/disinfection-of-tonometers-a-report-by-the-american-academy-of-ophthalmology
#8
Anna K Junk, Philip P Chen, Shan C Lin, Kouros Nouri-Mahdavi, Sunita Radhakrishnan, Kuldev Singh, Teresa C Chen
OBJECTIVE: To examine the efficacy of various disinfection methods for reusable tonometer prisms in eye care and to highlight how disinfectants can damage tonometer tips and cause subsequent patient harm. METHODS: Literature searches were conducted last in October 2016 in the PubMed and the Cochrane Library databases for original research investigations. Reviews, non-English language articles, nonophthalmology articles, surveys, and case reports were excluded. RESULTS: The searches initially yielded 64 unique citations...
July 11, 2017: Ophthalmology
https://www.readbyqxmd.com/read/28703924/chronic-kidney-disease-in-australian-hiv-infected-patients-analysis-of-the-australian-hiv-observational-database
#9
Jason Cheung, Rainer Puhr, Kathy Petoumenos, David A Cooper, Ian Woolley, Manoji Gunathilake, Nigel Raymond, Rick Varma, Catherine C O'Connor, David M Gracey
AIM: To examine data from the Australian HIV Observational Database (AHOD) to, firstly, describe the incidence of chronic kidney disease (CKD) and rate of loss of renal function in HIV-infected individuals living in Australia, and then to examine the risk factors contributing to CKD in this population. METHODS: AHOD patients over 18 years of age were eligible if they had at least two serum creatinine measurements from 1 April 2008 until 31 March 2016 and an initial estimated glomerular filtration rate (eGFR) greater than 60 mL/min/1...
July 13, 2017: Nephrology
https://www.readbyqxmd.com/read/28700530/retrospective-study-of-patients-on-etanercept-therapy-for-rheumatic-diseases-in-patients-with-chronic-hepatitis-c-virus
#10
Nisarg P Gandhi, Augustine M Manadan, Joel A Block
OBJECTIVE: Treatment of rheumatic diseases with concurrent hepatitis C virus (HCV) infection is a therapeutic challenge. Etanercept has no known hepatotoxicity; however there is a concern for worsening of HCV infection-related liver disease due to immunosuppressive action of the drug. Here, we retrospectively assessed the safety of etanercept in rheumatologic disease in patients with chronic HCV. METHODS: A retrospective review was conducted in patients with chronic HCV infection who received etanercept for diagnosis of rheumatoid arthritis and psoriatic arthritis...
July 11, 2017: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
https://www.readbyqxmd.com/read/28699096/hepatitis-c-cascade-of-care-among-pregnant-women-on-opioid-agonist-pharmacotherapy-attending-a-comprehensive-prenatal-program
#11
Kimberly Page, Lawrence Leeman, Steven Bishop, Sandra Cano, Ludmila N Bakhireva
Background Given the large increases in opioid use among pregnant women and associations with hepatitis C virus (HCV) infection, screening pregnant women who are on (opioid agonist) pharmacotherapy for HCV infection has potential to inform medical care for these mothers as well as their newborns. We investigated the HCV testing cascade among pregnant women on pharmacotherapy in order to describe exposure and infection rates and to identify opportunities that would improve care. Methods Secondary analyses of laboratory results were performed for HCV testing, including anti-HCV, viremia (RNA) and genotype...
July 11, 2017: Maternal and Child Health Journal
https://www.readbyqxmd.com/read/28698279/zika-virus-persistently-infects-and-is-basolaterally-released-from-primary-human-brain-microvascular-endothelial-cells
#12
Megan C Mladinich, John Schwedes, Erich R Mackow
Zika virus (ZIKV) is a mosquito-borne Flavivirus that has emerged as the cause of encephalitis and fetal microencephaly in the Americas. ZIKV uniquely persists in human bodily fluids for up to 6 months, is sexually transmitted, and traverses the placenta and the blood-brain barrier (BBB) to damage neurons. Cells that support persistent ZIKV replication and mechanisms by which ZIKV establishes persistence remain enigmatic but central to ZIKV entry into protected neuronal compartments. The endothelial cell (EC) lining of capillaries normally constrains transplacental transmission and forms the BBB, which selectively restricts access of blood constituents to neurons...
July 11, 2017: MBio
https://www.readbyqxmd.com/read/28692470/is-annual-volume-enough-the-role-of-experience-and-specialization-on-inpatient-mortality-after-hepatectomy
#13
Daniel A Hashimoto, Yanik J Bababekov, Winta T Mehtsun, Sahael M Stapleton, Andrew L Warshaw, Keith D Lillemoe, David C Chang, Parsia A Vagefi
OBJECTIVE: To investigate the effect of subspecialty practice and experience on the relationship between annual volume and inpatient mortality after hepatic resection. BACKGROUND: The impact of annual surgical volume on postoperative outcomes has been extensively examined. However, the impact of cumulative surgeon experience and specialty training on this relationship warrants investigation. METHODS: The New York Statewide Planning and Research Cooperative System inpatient database was queried for patients' ≥18 years who underwent wedge hepatectomy or lobectomy from 2000 to 2014...
July 7, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28690615/impact-of-early-life-exposures-to-infections-antibiotics-and-vaccines-on-perinatal-and-long-term-health-and-disease
#14
REVIEW
Steven L Raymond, Jaimar C Rincon, James L Wynn, Lyle L Moldawer, Shawn D Larson
Essentially, all neonates are exposed to infections, antibiotics, or vaccines early in their lives. This is especially true for those neonates born underweight or premature. In contrast to septic adults and children who are at an increased risk for subsequent infections, exposure to infection during the neonatal period is not associated with an increased risk of subsequent infection and may be paradoxically associated with reductions in late-onset sepsis (LOS) in the most premature infants. Perinatal inflammation is also associated with a decreased incidence of asthma and atopy later in life...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28689442/drug-interactions-in-hiv-infected-patients-treated-for-hepatitis-c
#15
Vicente Soriano, Pablo Labarga, José V Fernandez-Montero, Carmen de Mendoza, Laura Benítez-Gutiérrez, José M Peña, Pablo Barreiro
The introduction of direct-acting antivirals (DAA) has revolutionized the hepatitis C field. Most hepatitis C patients can now be cured, including those coinfected with HIV. However, drug-drug interactions (DDI) between DAA and antiretrovirals (ARV) should be known to prevent either toxicity due to drug overexposure or treatment failures due to low drug concentrations. Areas covered: Clinically significant DDI may be classified as major (when co-administration should be contraindicated) or minor (when they require close monitoring, changes in drug dosage or in timing)...
July 13, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28689333/the-ribavirin-pregnancy-registry-an-interim-analysis-of-potential-teratogenicity-at-the-mid-point-of-enrollment
#16
Susan M Sinclair, Judith K Jones, Richard K Miller, Michael F Greene, Paul Y Kwo, Willis C Maddrey
INTRODUCTION: Significant teratogenic effects have been demonstrated in all animal species exposed to ribavirin. Ribavirin is prescribed for chronic hepatitis C and is contraindicated in women who are pregnant and in the male sexual partners of women who are pregnant. Both sexes are advised to avoid pregnancy for 6 months after exposure. The Ribavirin Pregnancy Registry was established in 2003 to monitor pregnancy exposures to ribavirin for signals of possible human teratogenicity. METHODS: This voluntary registry enrolls pregnant women with prenatal exposure to ribavirin...
July 8, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/28688807/modulation-of-hepatic-glutathione-transferases-isoenzymes-in-three-bivalve-species-exposed-to-purified-microcystin-lr-and-microcystis-extracts
#17
M Carneiro, P Antas, B Reis, J Azevedo, H Osório, A Campos, V Vasconcelos, J C Martins
This study compares the role of hepatic cytosolic glutathione transferases (cGST) isoforms of three different bivalve species to a Microcystis aeruginosa extract and purified MC-LR exposure (both at 150 μg MC-LR L(-1)) for 24 h. Characterization and alterations of the cytosolic GST activities in Mytilus galloprovincialis, Ruditapes philippinarum and Corbicula fluminea were measured using four class-specific substrates and changes in individual GST isoforms expression were achieved by a subsequent two-dimensional electrophoresis analysis...
July 5, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28688001/pharmacokinetic-interactions-and-safety-of-coadministration-of-glecaprevir-and-pibrentasvir-in-healthy-volunteers
#18
Chih-Wei Lin, Sandeep Dutta, Weihan Zhao, Armen Asatryan, Andrew Campbell, Wei Liu
BACKGROUND AND OBJECTIVE: Glecaprevir and pibrentasvir are pangenotypic direct-acting antiviral agents for the treatment of chronic hepatitis C virus infection. The aim of the present study was to evaluate the drug-drug interaction and safety of glecaprevir and pibrentasvir coadministration in healthy volunteers. METHODS: In this open-label, randomized, multiple-dose, Phase 1 study in 72 subjects, glecaprevir (100-1200 mg once daily) and pibrentasvir (40-200 mg once daily) were administered alone for 7 days and then in combination for another 7 days...
July 7, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28687643/cancer-incidence-attributable-to-lifestyle-and-environmental-factors-in-alberta-in-2012-summary-of-results
#19
Anne Grundy, Abbey E Poirier, Farah Khandwala, Xin Grevers, Christine M Friedenreich, Darren R Brenner
BACKGROUND: Estimates of the proportion of cancer cases that can be attributed to modifiable risk factors are not available for Canada and, more specifically, Alberta. The purpose of this study was to estimate the total proportion of cancer cases in Alberta in 2012 that could be attributed to a set of 24 modifiable lifestyle and environmental risk factors. METHODS: We estimated summary population attributable risk estimates for 24 risk factors (smoking [both passive and active], overweight and obesity, inadequate physical activity, diet [inadequate fruit and vegetable consumption, inadequate fibre intake, excess red and processed meat consumption, salt consumption, inadequate calcium and vitamin D intake], alcohol, hormones [oral contraceptives and hormone therapy], infections [Epstein-Barr virus, hepatitis B and C viruses, human papillomavirus, Helicobacter pylori], air pollution, natural and artificial ultraviolet radiation, radon and water disinfection by-products) by combining population attributable risk estimates for each of the 24 factors that had been previously estimated...
July 7, 2017: CMAJ Open
https://www.readbyqxmd.com/read/28686624/adverse-effects-of-chronic-exposure-to-nonylphenol-on-non-alcoholic-fatty-liver-disease-in-male-rats
#20
Jie Yu, Xuesong Yang, Ya Luo, Xuefeng Yang, Mengxue Yang, Jin Yang, Jie Zhou, Feng Gao, Liting He, Jie Xu
Endocrine-disrupting chemical (EDC) has been thought to play a role in non-alcoholic fatty liver disease (NAFLD). However, the toxic effects of Nonylphenol (NP), an EDC, on non-alcoholic fatty liver disease have never been elaborated. This study aimed to investigate whether exposure to NP could induce NAFDL, a promoting effect of high-sucrose-high-fat diet (HSHFD) on the adverse effects caused by NP was evaluated. Fourth eight male rats were assigned to four groups and each group was treated with a specific testing sample: normal-diet (ND) control group (C-ND); normal diet plus NP (180mg/kg/day) group (NP-ND); high-sucrose-high-fat-diet control group (C-HSHFD); HSHFD plus NP (180mg/kg/day) group (NP-HSHFD)...
2017: PloS One
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