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https://www.readbyqxmd.com/read/30557903/pharmacokinetics-and-important-drug-drug-interactions-to-remember-when-treating-advanced-chronic-kidney-disease-patients-with-hepatitis-c-direct-acting-anti-viral-therapy
#1
Elizabeth Cohen, AnnMarie Liapakis
Hepatitis C direct acting antiviral (DAA) therapy has evolved so that infected patients with advanced chronic kidney disease (CKD) can now anticipate the opportunity for sustained virologic response equivalent to that of the broader population of patients with hepatitis C. This has revolutionized the field of transplantation as it relates to renal transplant candidates with hepatitis C and the use of grafts from hepatitis C virus (HCV) viremic donors. In treating this population of patients, special consideration must be given to the timing of anti-viral therapy and drug-drug interactions...
December 17, 2018: Seminars in Dialysis
https://www.readbyqxmd.com/read/30557576/metal-chelators-for-the-inhibition-of-the-lymphocytic-choriomeningitis-virus-endonuclease-domain
#2
Magali Saez-Ayala, Elsie Laban Yekwa, Clémence Mondielli, Loic Roux, Sergio Hernández, Fabrice Bailly, Philippe Cotelle, Dominga Rogolino, Bruno Canard, François Ferron, Karine Alvarez
Arenaviridae is a viral family whose members are associated with rodent-transmitted infections to humans responsible of severe diseases. The current lack of a vaccine and limited therapeutic options make the development of efficacious drugs of high priority. The cap-snatching mechanism of transcription of Arenavirus performed by the endonuclease domain of the L-protein is unique and essential, so we developed a drug design program targeting the endonuclease activity of the prototypic Lymphocytic ChorioMeningitis Virus...
December 14, 2018: Antiviral Research
https://www.readbyqxmd.com/read/30557324/hepatitis-e-virus-seroprevalence-and-determinants-in-various-study-populations-in-the-netherlands
#3
C J Alberts, M F Schim van der Loeff, S Sadik, F R Zuure, E J A J Beune, M Prins, M B Snijder, S M Bruisten
BACKGROUND: The epidemiology of hepatitis E virus (HEV) is not fully understood. In this study, we assessed putative risk factors for HEV seropositivity in various study populations in the Netherlands. METHODS: Data and samples from five different study populations were analysed: (A) blood donors (n = 5,239), (B) adults reporting a vegetarian life style since the age of 12 years (n = 231), (C) residents of Amsterdam, the Netherlands, with different ethnic backgrounds (n = 1,198), (D) men who have sex with men (MSM) (HIV positive and HIV negative) (n = 197), and (E) persons who use drugs (PWUD) (HIV positive and HIV negative) (n = 200)...
2018: PloS One
https://www.readbyqxmd.com/read/30554131/synthesis-structure-activity-relationship-and-in-vitro-anti-influenza-virus-activity-of-novel-polyphenol-pentacyclic-triterpene-conjugates
#4
Haiwei Li, Man Li, Renyang Xu, Shouxin Wang, Yongmin Zhang, Lihe Zhang, Demin Zhou, Sulong Xiao
It is urgently necessary to develop more effective anti-influenza agents due to the continuous emergence of drug-resistant strains of influenza virus. Our earlier studies have identified that certain pentacyclic triterpene derivatives are effective inhibitors of influenza virus infection. In the present study, a series of C-28 modified pentacyclic triterpene derivatives via conjugation with a series of polyphenols were synthesized, and their antiviral activities against influenza A/WSN/33 (H1N1) virus in MDCK (Madin-Darby canine kidney) cells were evaluated...
December 7, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/30552954/non-covalent-hitchhiking-on-endogenous-carriers-as-a-protraction-mechanism-for-antiviral-macromolecular-prodrugs
#5
Camilla Kaas Frich, Franziska Krüger, Raoul Walther, Cecilie Domar, Anna H F Andersen, Anne Tvilum, Frederik Dagnæs-Hansen, Paul W Denton, Martin Tolstrup, Søren R Paludan, Jan Münch, Alexander N Zelikin
Albumin is a highly successful tool of drug delivery providing drastically extended body and blood residence time for the associated cargo, but it only traffics single drug copies at a time. In turn, macromolecular prodrugs (MP) are advantaged in carrying a high drug payload but offering only a modest extension of residence time to the conjugated drugs. In this work, we engineer MP to contain terminal groups that bind to albumin via non-covalent association and reveal that this facile measure affords a significant protraction for the associated polymers...
December 12, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30552635/recent-progress-on-functional-genomics-research-of-enterovirus-71
#6
REVIEW
Huiqiang Wang, Yuhuan Li
Enterovirus 71 (EV71) is one of the main pathogens that causes hand-foot-and-mouth disease (HFMD). HFMD caused by EV71 infection is mostly self-limited; however, some infections can cause severe neurological diseases, such as aseptic meningitis, brain stem encephalitis, and even death. There are still no effective clinical drugs used for the prevention and treatment of HFMD. Studying EV71 protein function is essential for elucidating the EV71 replication process and developing anti-EV71 drugs and vaccines. In this review, we summarized the recent progress in the studies of EV71 non-coding regions (5' UTR and 3' UTR) and all structural and nonstructural proteins, especially the key motifs involving in viral infection, replication, and immune regulation...
December 14, 2018: Virologica Sinica
https://www.readbyqxmd.com/read/30552141/ribavirin-induced-downregulation-of-ccaat-enhancer-binding-protein-%C3%AE-leads-to-suppression-of-lipogenesis
#7
Shinya Satoh, Daichi Onomura, Youki Ueda, Hiromichi Dansako, Masao Honda, Shuichi Kaneko, Nobuyuki Kato
Recently we demonstrated that the anti-viral drug ribavirin (RBV) had the ability to suppress lipogenesis through downregulation of retinoid X receptor α (RXRα) under control of the intracellular GTP-level and AMP-activated protein kinase-related kinases, especially microtubule affinity regulating kinase 4 (MARK4). RXRα-overexpression attenuated but did not abolish lipogenesis suppression by RBV, implying that additional factor(s) were involved in this suppressive effect. In this study, we found that the protein level, but not the mRNA level, of CCAAT/enhancer-binding protein α (C/EBPα) was downregulated by RBV in hepatic cells...
December 14, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/30550348/pulmonary-hypertension-in-patients-with-a-history-of-intravenous-drug-use
#8
Michael McGee, Nicholas Whitehead, Scott Twadell, Nicholas Collins
OBJECTIVE: Pulmonary hypertension may be a consequence of intrinsic elevation in pulmonary vasculature resistance or complicate numerous other conditions affecting the cardiac and respiratory systems. In this review we sought to explore the relationship between pulmonary hypertension and intravenous drug use. METHODS: A narrative review was conducted using PubMed MeSH search with further papers were identified using a standard PubMed search with relevant key terms and various synonyms...
December 14, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/30548320/editorial-comorbidities-concomitant-medications-and-potential-drug-drug-interactions-with-interferon-free-direct-acting-anti-viral-agents-in-chronic-hepatitis-c-authors-reply
#9
EDITORIAL
Chen-Hua Liu, Jia-Horng Kao
No abstract text is available yet for this article.
January 2019: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30548317/editorial-comorbidities-concomitant-medications-and-potential-drug-drug-interactions-with-interferon-free-direct-acting-anti-viral-agents-in-chronic-hepatitis-c
#10
EDITORIAL
Naoto Kawabe, Senju Hashimoto, Kentaro Yoshioka
No abstract text is available yet for this article.
January 2019: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30541831/verdinexor-kpt-335-a-selective-inhibitor-of-nuclear-export-reduces-rsv-replication-in-vitro
#11
Patricia A Jorquera, Cynthia Mathew, Jennifer Pickens, Colin Williams, Jasmina M Luczo, Sharon Tamir, Reena Ghildyal, Ralph A Tripp
Respiratory syncytial virus (RSV) is a leading cause of hospitalization of infants and young children causing considerable respiratory disease and repeat infections that may lead to chronic respiratory conditions such as asthma, wheezing, and bronchitis. RSV causes ∼34 million new episodes of lower respiratory tract illness (LTRI) in children younger than 5 years of age with >3 million hospitalizations due to severe RSV-associated LRTI. The standard of care is limited to symptomatic relief as there are no approved vaccines and few effective antiviral drugs, thus a safe and efficacious RSV therapeutic is needed...
December 12, 2018: Journal of Virology
https://www.readbyqxmd.com/read/30536875/human-anti-nkp46-antibody-for-studies-of-nkp46-dependent-nk-cell-function-and-its-applications-for-type-1-diabetes-and-cancer-research
#12
Orit Berhani, Ariella Glasner, Shira Kahlon, Alexandra Duev-Cohen, Rachel Yamin, Elad Horwitz, Jonatan Enk, Ofra Moshel, Alexandar Varvak, Angel Porgador, Stipan Jonjic, Ofer Mandelboim
Natural Killer (NK) cells are innate lymphocytes that efficiently eliminate cancerous and infected cells. NKp46 is an important NK activating receptor shown to participate in recognition and activation of NK cells against pathogens, tumor cells, virally infected cells, and self-cells in autoimmune conditions, including type I and II diabetes. However, some of the NKp46 ligands are unknown and therefore investigating human NKp46 activity and its critical role in NK cell biology is problematic. We developed a unique anti-human NKp46 monocloncal antibody, denoted hNKp46...
December 7, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/30535524/anti-trichomonas-vaginalis-activity-of-chalcone-and-amino-analogues
#13
Márcia Rodrigues Trein, Lígia Rodrigues E Oliveira, Graziela Vargas Rigo, Mayara Aparecida Rocha Garcia, Brenda Petro-Silveira, Danielle da Silva Trentin, Alexandre José Macedo, Luis Octávio Regasini, Tiana Tasca
Trichomoniasis is the most common non-viral sexually transmitted disease worldwide and can lead to serious consequences in reproductive health, cancer, and HIV acquisition. The current approved treatment present adverse effects and drug resistance data on this neglected parasitic infection is underestimated. Chalcones are a family of molecules that present biological applications, such as activity against many pathogenic organisms including protozoan pathogens. Chalcone (1) and three amino-analogues (2-4) were synthesized by Claisen-Schmidt condensation reaction and had their activity evaluated against the parasitic protozoan Trichomonas vaginalis...
December 7, 2018: Parasitology Research
https://www.readbyqxmd.com/read/30530622/anti-claudin-antibodies-as-a-concept-for-development-of-claudin-directed-drugs
#14
Yosuke Hashimoto, Yoshiaki Okada, Keisuke Shirakura, Keisuke Tachibana, Makoto Sawada, Kiyohito Yagi, Takefumi Doi, Masuo Kondoh
Claudin (CLDN) proteins, a tetra-transmembrane family containing over 20 members, have been identified as a key structural and functional component of intercellular seals, tight junctions (TJs). CLDNs are involved in the barrier and fence functions of TJs. Loosening the TJ barrier is one strategy for increasing drug absorption and delivery to the brain. Due to aberrant CLDN expression, the TJ fence function is frequently dysregulated in carcinogenesis. In addition, CLDN-1 is a co-receptor for the hepatitis C virus...
December 7, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/30530599/endonuclease-activity-inhibition-of-the-ns1-protein-of-parvovirus-b19-as-a-novel-target-for-antiviral-drug-development
#15
Peng Xu, Safder S Ganaie, Xiaomei Wang, Zekun Wang, Steve Kleiboeker, Nancy C Horton, Richard F Heier, Marvin J Meyers, John E Tavis, Jianming Qiu
Human parvovirus B19 (B19V), a member of the genus Erythroparvovirus of the family Parvoviridae , is a small non-enveloped virus that has a single-stranded DNA (ssDNA) genome of 5.6 kilobases with two inverted terminal repeats (ITRs). B19V infection often results in severe hematological disorders and fetal death in humans. B19V replication follows a model of rolling hairpin-dependent DNA replication, in which the large non-structural protein NS1 introduces a site-specific single strand nick in the viral DNA replication origins, which locate at the ITRs...
December 10, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/30529191/effects-of-inorganic-nanoparticles-on-liver-fibrosis-optimizing-a-double-edged-sword-for-therapeutics
#16
REVIEW
Jie Kai Tee, Fei Peng, Han Kiat Ho
Liver fibrosis is a condition of sustained wound healing in response to chronic liver injury caused by various factors such as viral, cholestatic and inflammatory diseases. Despite significant advances in the understanding of the mechanistic details of fibrosis, therapeutic intervention with the use of anti-fibrotic drugs achieved only marginal efficacy. Among which, pharmacokinetics profile of agents leading to off-targeting and suboptimal distribution are the principal limiting factors. Concurrently, inorganic nanoparticles (NPs) have gained significant recognition in biomedicine, owning to their unique physicochemical properties...
December 6, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/30516045/contemporary-anti-ebola-drug-discovery-approaches-and-platforms
#17
Elena K Schneider-Futschik, Daniel Hoyer, Alex Khromykh, Jonathan B Baell, Glenn Marsh, Mark A Baker, Jian Li, Tony Velkov
The Ebola virus has a grave potential to destabilise civil society as we know it. The past few deadly Ebola outbreaks were unprecedented in size: the virus spread from the epicentres of Guinea, Sierra Leone, Nigeria and Liberia. The 2014-15 Ebola West Africa outbreak was associated with almost 30,000 suspected or confirmed cases and over 11,000 documented deaths. There is a general acceptance within the World Health Organisation (WHO) and the Ebola outbreak response community that future outbreaks will become increasingly more frequent and more likely to involve inter-continental transmission...
December 5, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/30514402/preclinical-pharmacokinetic-evaluation-to-facilitate-repurposing-of-tyrosine-kinase-inhibitors-nilotinib-and-imatinib-as-antiviral-agents
#18
Hari Krishna Ananthula, Scott Parker, Erin Touchette, R Mark Buller, Gopi Patel, Daniel Kalman, Johanna S Salzer, Nadia Gallardo-Romero, Victoria Olson, Inger K Damon, Tessa Moir-Savitz, Larry Sallans, Milton H Werner, Catherine M Sherwin, Pankaj B Desai
BACKGROUND: Several tyrosine kinase inhibitors (TKIs) developed as anti-cancer drugs, also have anti-viral activity due to their ability to disrupt productive replication and dissemination in infected cells. Consequently, such drugs are attractive candidates for "repurposing" as anti-viral agents. However, clinical evaluation of therapeutics against infectious agents associated with high mortality, but low or infrequent incidence, is often unfeasible. The United States Food and Drug Administration formulated the "Animal Rule" to facilitate use of validated animal models for conducting anti-viral efficacy studies...
December 4, 2018: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/30514185/discovery-of-dengue-virus-inhibitors
#19
Adib Afandi Abdullah, Yean Kee Lee, Sek Peng Chin, See Khai Lim, Vannajan Lee, Rozana Othman, Shatrah Othman, Noorsaadah Abdul Rahman, Rohana Yusof, Choon Han Heh
To date, there is still no approved anti-dengue agent to treat dengue infection in the market. Although the only licensed dengue vaccine, Dengvaxia is available, its protective efficacy against serotypes 1 and 2 of dengue virus was reported to be lower than serotypes 3 and 4. Moreover, according to WHO, the risk of being hospitalized and having severe dengue increased in seronegative individuals after they received Dengvaxia vaccination. Nevertheless, various studies had been carried out in search of dengue virus inhibitors...
December 4, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/30504327/novel-insights-and-therapeutic-approaches-in-idiopathic-multicentric-castleman-disease
#20
REVIEW
David C Fajgenbaum
Castleman disease (CD) describes a heterogeneous group of hematologic disorders that share characteristic lymph node histopathology. Patients of all ages present with either a solitary enlarged lymph node (unicentric CD) or multicentric lymphadenopathy (MCD) with systemic inflammation, cytopenias, and life-threatening multiple organ dysfunction resulting from a cytokine storm often driven by interleukin 6 (IL-6). Uncontrolled human herpesvirus-8 (HHV-8) infection causes approximately 50% of MCD cases, whereas the etiology is unknown in the remaining HHV-8-negative/idiopathic MCD cases (iMCD)...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
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