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https://www.readbyqxmd.com/read/28918038/strategies-for-in%C3%A2-vivo-screening-and-mitigation-of-hepatotoxicity-associated-with-antisense-drugs
#1
Piotr J Kamola, Klio Maratou, Paul A Wilson, Kay Rush, Tanya Mullaney, Tom McKevitt, Paula Evans, Jim Ridings, Probash Chowdhury, Aude Roulois, Ann Fairchild, Sean McCawley, Karen Cartwright, Nigel J Gooderham, Timothy W Gant, Kitty Moores, Stephen A Hughes, Mark R Edbrooke, Kenneth Clark, Joel D Parry
Antisense oligonucleotide (ASO) gapmers downregulate gene expression by inducing enzyme-dependent degradation of targeted RNA and represent a promising therapeutic platform for addressing previously undruggable genes. Unfortunately, their therapeutic application, particularly that of the more potent chemistries (e.g., locked-nucleic-acid-containing gapmers), has been hampered by their frequent hepatoxicity, which could be driven by hybridization-mediated interactions. An early de-risking of this liability is a crucial component of developing safe, ASO-based drugs...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917534/modeling-the-modified-drug-release-from-curved-shape-drug-delivery-systems-dome-matrix-%C3%A2
#2
D Caccavo, A A Barba, M d'Amore, R De Piano, G Lamberti, A Rossi, P Colombo
The controlled drug release from hydrogel-based drug delivery systems is a topic of large interest for research in pharmacology. The mathematical modeling of the behavior of these systems is a tool of emerging relevance, since the simulations can be of use in the design of novel systems, in particular for complex shaped tablets. In this work a model, previously developed, was applied to complex-shaped oral drug delivery systems based on hydrogels (Dome Matrix®). Furthermore, the model was successfully adopted in the description of drug release from partially accessible Dome Matrix® systems (systems with some surfaces coated)...
September 13, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28917389/alternative-treatment-strategies-for-catatonia-a-systematic-review
#3
REVIEW
Scott R Beach, Federico Gomez-Bernal, Jeff C Huffman, Gregory L Fricchione
BACKGROUND: Catatonia is a commonly encountered syndrome, affecting 10-20% of various psychiatric populations and carrying significant medical co-morbidities. However, there are few established alternative treatment strategies when benzodiazepines are ineffective and electroconvulsive therapy is unavailable. OBJECTIVE: The authors systematically review evidence for alternative treatment strategies for catatonia using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines...
September 2017: General Hospital Psychiatry
https://www.readbyqxmd.com/read/28916103/controlled-synchronized-actuation-of-microdroplets-by-gravity-in-a-superhydrophobic-3d-printed-device
#4
P E Oomen, J P S H Mulder, E Verpoorte, R D Oleschuk
Droplet manipulation over open surfaces allows one to perform assays with a large degree of control and high throughput, making them appealing for applications in drug screening or (bio)analysis. However, the design, manufacturing and operation of these systems comes with high technical requirements. In this study we employ a commercial, low-friction, superhydrophobic coating, Ultra-Ever Dry(®), on a 3D-printed microfluidic device. The device features individual droplet compartments, which allow the manipulation of discrete droplets (10-50 μL) actuated by gravity alone...
October 2, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28914446/risk-factors-for-thiopurine-induced-myelosuppression-and-infections-in-inflammatory-bowel-disease-patients-with-a-normal-tpmt-genotype
#5
M M T J Broekman, M J H Coenen, G J Wanten, C J van Marrewijk, O H Klungel, A L M Verbeek, P M Hooymans, H-J Guchelaar, H Scheffer, L J J Derijks, D R Wong, D J de Jong
BACKGROUND: Leucopenia is a common side effect in patients treated with thiopurines. Variants in the thiopurine S-methyltransferase (TPMT) gene are the best-known risk factor, but only explain up to 25% of leucopenia cases. AIM: To identify the clinical risk factors for thiopurine-induced leucopenia in patients without a common TPMT variant, and explore if these patients are at increased risk for infections. METHODS: Post hoc analysis of the Thiopurine response Optimisation by Pharmacogenetic testing in Inflammatory bowel disease Clinics (TOPIC) trial...
September 15, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28913747/primary-sj%C3%A3-gren-s-syndrome-extraglandular-manifestations-and-hydroxychloroquine-therapy
#6
J Demarchi, S Papasidero, M A Medina, D Klajn, R Chaparro Del Moral, O Rillo, V Martiré, G Crespo, A Secco, A Catalan Pellet, C Amitrano, C Crow, C Asnal, P Pucci, F Caeiro, N Benzanquen, J P Pirola, M Mayer, F Zazzetti, S Velez, J Barreira, N Tamborenea, L Santiago, L Raiti
The use of hydroxychloroquine (HCQ) in Primary Sjögren's Syndrome (pSS) has been assessed in different studies over the last years, with conflicting results regarding its efficacy in sicca syndrome and extraglandular manifestations (EGM). The goal of this study was to compare the incidence rate of EGM in pSS patients with and without HCQ therapy.We performed a multicenter retrospective study, including patients with pSS (European classification criteria) with at least 1 year of follow-up. Subjects with concomitant fibromyalgia, autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis were excluded...
September 14, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28912477/brain-barriers-and-functional-interfaces-with-sequential-appearance-of-abc-efflux-transporters-during-human-development
#7
Kjeld Møllgård, Katarzyna M Dziegielewska, Camilla B Holst, Mark D Habgood, Norman R Saunders
Adult brain is protected from entry of drugs and toxins by specific mechanisms such as ABC (ATP-binding Cassette) efflux transporters. Little is known when these appear in human brain during development. Cellular distribution of three main ABC transporters (ABCC1, ABCG2, ABCB1) was determined at blood-brain barriers and interfaces in human embryos and fetuses in first half of gestation. Antibodies against claudin-5 and -11 and antibodies to α-fetoprotein were used to describe morphological and functional aspects of brain barriers...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912242/fabrication-of-fillable-microparticles-and-other-complex-3d-microstructures
#8
Kevin J McHugh, Thanh D Nguyen, Allison R Linehan, David Yang, Adam M Behrens, Sviatlana Rose, Zachary L Tochka, Stephany Y Tzeng, James J Norman, Aaron C Anselmo, Xian Xu, Stephanie Tomasic, Matthew A Taylor, Jennifer Lu, Rohiverth Guarecuco, Robert Langer, Ana Jaklenec
Three-dimensional (3D) microstructures created by microfabrication and additive manufacturing have demonstrated value across a number of fields, ranging from biomedicine to microelectronics. However, the techniques used to create these devices each have their own characteristic set of advantages and limitations with regards to resolution, material compatibility, and geometrical constraints that determine the types of microstructures that can be formed. We describe a microfabrication method, termed StampEd Assembly of polymer Layers (SEAL), and create injectable pulsatile drug-delivery microparticles, pH sensors, and 3D microfluidic devices that we could not produce using traditional 3D printing...
September 15, 2017: Science
https://www.readbyqxmd.com/read/28911730/management-of-tyrosine-kinase-inhibitors-tki-side-effects-in-differentiated-and-medullary-thyroid-cancer-patients
#9
REVIEW
C Resteghini, S Cavalieri, D Galbiati, R Granata, S Alfieri, C Bergamini, P Bossi, L Licitra, L D Locati
Four tyrosine kinase inhibitors (TKIs) have been recently licensed in thyroid cancer (TC), sorafenib and lenvatinib for differentiated TC, vandetanib and cabozantinib for medullary TC. Others TKIs such as axitinib, pazopanib, sunitinib, have been tested within phase II trials. The toxicity burden associated to TKIs is not negligible. Drug reductions and interruptions are common, definitive drug withdrawals have also been reported as well as toxic deaths in more rare cases. In this context, the prevention of toxicities is mandatory to allow patients to stay on treatment as long as possible without dose and schedule modifications...
June 2017: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/28911362/assessment-of-the-quality-of-anti-tuberculosis-medicines-in-almaty-kazakhstan-2014
#10
D Nabirova, G Schmid, R Yusupova, M Kantarbayeva, S I Ismailov, D Moffett, R W O Jähnke, J P Nuorti
SETTING: In 2009, the World Health Organization (WHO) conducted a survey of the quality of four anti-tuberculosis drugs in the former Soviet Union countries. Kazakhstan had the highest proportion of substandard drugs. OBJECTIVE: To assess the quality of anti-tuberculosis drugs used in Kazakhstan in 2014. DESIGN: Fourteen anti-tuberculosis drugs from the Almaty Interdistrict TB Dispensary were randomly selected and screened for quality using Global Pharma Health Fund Minilab™ testing...
October 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28911309/formulation-quality-control-and-safety-issues-of-nanocarriers-used-for-cancer-treatment
#11
Ismael D Bianco, Marcelo R Ceballos, Cristian Casado, Viviana G Dabbene, Carolina Rizzi, R Kiyomi Mizutamari
Cancer is becoming a leading cause of death in the last years. Although we have seen great advances, most human cancers remain incurable because many patients either do not respond or relapse to treatment. Several lines of research are disclosing new therapeutic targets which lead to new active drugs. However, there are still unsolved problems related to stabilization of the pharmaceutical ingredient in aqueous and biological media, pharmacokinetic and pharmacodynamic profiles and cellular uptake to name just a few...
June 7, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28910350/phylogeographic-genomic-and-meropenem-susceptibility-analysis-of-burkholderia-ubonensis
#12
Erin P Price, Derek S Sarovich, Jessica R Webb, Carina M Hall, Sierra A Jaramillo, Jason W Sahl, Mirjam Kaestli, Mark Mayo, Glenda Harrington, Anthony L Baker, Lindsay C Sidak-Loftis, Erik W Settles, Madeline Lummis, James M Schupp, John D Gillece, Apichai Tuanyok, Jeffrey Warner, Joseph D Busch, Paul Keim, Bart J Currie, David M Wagner
The bacterium Burkholderia ubonensis is commonly co-isolated from environmental specimens harbouring the melioidosis pathogen, Burkholderia pseudomallei. B. ubonensis has been reported in northern Australia and Thailand but not North America, suggesting similar geographic distribution to B. pseudomallei. Unlike most other Burkholderia cepacia complex (Bcc) species, B. ubonensis is considered non-pathogenic, although its virulence potential has not been tested. Antibiotic resistance in B. ubonensis, particularly towards drugs used to treat the most severe B...
September 14, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28910186/applying-the-problem-behavior-theory-to-adolescent-drug-use-among-a-cross-sectional-sample-of-boys-participating-in-a-community-based-youth-organization
#13
Adam C Alexander, Christopher O Obong'o, Prachi Chavan, Mark W Vander Weg, Kenneth D Ward
BACKGROUND: Drug use remains an important public health concern in the United States, and understanding drug use among young adolescents is vital towards improving the health of the population. OBJECTIVE: This study applied the Problem Behavior Theory (PBT) to lifetime drug use among a cross-sectional sample of Boy Scouts (N = 770). The PBT provides a conceptual framework for identifying risk and protective factors for adolescent problem behaviors, including drug use...
September 14, 2017: Substance Use & Misuse
https://www.readbyqxmd.com/read/28906150/safety-and-efficacy-of-a-ttr-specific-antisense-oligonucleotide-in-patients-with-transthyretin-amyloid-cardiomyopathy
#14
Merrill D Benson, Noel R Dasgupta, Stacy M Rissing, Jessica Smith, Harvey Feigenbaum
OBJECTIVES: Cardiomyopathy is a major cause of death in both the hereditary form of transthyretin (TTR) amyloidosis and the sporadic late-age-onset transthyretin amyloidosis (ATTR wild-type (ATTRwt)). Clinically disease progression from time of diagnosis to death is usually quoted as 5- to 15-years. In prior studies, significant progression of cardiac parameters in patients with moderate to severe cardiomyopathy has been noted within a 12-month time span. METHODS: The present study was designed to prospectively monitor changes in cardiac parameters, both structural and functional, in patients with ATTR cardiomyopathy while treated with a TTR specific antisense oligonucleotide (ASO; IONIS-TTR℞) designed to lower blood levels of the amyloid fibril precursor protein...
September 14, 2017: Amyloid: the International Journal of Experimental and Clinical Investigation
https://www.readbyqxmd.com/read/28905282/comparison-of-reporting-phase-i-trial-results-in-clinicaltrials-gov-and-matched-publications
#15
REVIEW
D Shepshelovich, H Goldvaser, L Wang, A R Abdul Razak, P L Bedard
Background Data on completeness of reporting of phase I cancer clinical trials in publications are lacking. Methods The ClinicalTrials.gov database was searched for completed adult phase I cancer trials with reported results. PubMed was searched for matching primary publications published prior to November 1, 2016. Reporting in primary publications was compared with the ClinicalTrials.gov database using a 28-point score (2=complete; 1=partial; 0=no reporting) for 14 items related to study design, outcome measures and safety profile...
September 14, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28905092/drug-induced-oral-lichenoid-reactions-a-real-clinical-entity-a-systematic-review
#16
REVIEW
Giulio Fortuna, Massimo Aria, Julie H Schiavo
PURPOSE: Drug-induced oral lichenoid reactions (DIOLRs) have been extensively reported in the literature, but the validity of the causality relationship between any drug and the oral lichenoid lesions (OLLs) still remains questionable. We sought to determine whether this causality relationship really exists, whether a resolution of the oral lesions upon withdrawal occurs, and what the most common alleged offending medications are. METHODS: Nine electronic databases from January 1966 to December 2016 were systematically searched to identify all relevant studies selected with specific inclusion criteria (a clinical and histopathological diagnosis of DIOLRs, and clearly statement on the systemic offending medication)...
September 13, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28904428/collapsing-glomerulopathy-a-troublemaker-for-the-renal-allograft-lessons-learnt
#17
K V Kanodia, A V Vanikar, L K Nigam, R D Patel, K S Suthar, H V Patel, H L Trivedi
Collapsing glomerulopathy (CG) is a well-recognized distinct morphological pattern of proliferative parenchymal injury leading to rapid graft failure. We conducted a single-center retrospective study to evaluate the prevalence, clinicopathological features, and prognosis of CG in renal transplant recepient. We analyzed 2518 renal allograft biopsies performed from 2007 to 2015 and correlated their clinicopathological features. The prevalence of CG was 0.83% (21 out of 2518) of allograft biopsies with a higher prevalence of 1...
September 2017: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/28903507/cd4-cd8-ratio-and-cd8-count-as-prognostic-markers-for-mortality-in-human-immunodeficiency-virus-infected-patients-on-antiretroviral-therapy-the-antiretroviral-therapy-cohort-collaboration-art-cc
#18
Adam Trickey, Margaret T May, Philipp Schommers, Jan Tate, Suzanne M Ingle, Jodie L Guest, M John Gill, Robert Zangerle, Mike Saag, Peter Reiss, Antonella d'Arminio Monforte, Margaret Johnson, Viviane D Lima, Tim R Sterling, Matthias Cavassini, Linda Wittkop, Dominique Costagliola, Jonathan A C Sterne
Background: We investigated whether CD4:CD8 ratio and CD8 count were prognostic for all-cause, AIDS, and non-AIDS mortality in virologically suppressed patients with high CD4 count. Methods: We used data from 13 European and North American cohorts of human immunodeficiency virus-infected, antiretroviral therapy (ART)-naive adults who started ART during 1996-2010, who were followed from the date they had CD4 count ≥350 cells/μL and were virologically suppressed (baseline)...
September 15, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28901476/dadle-improves-hepatic-ischemia-reperfusion-injury-in-mice-via-activation-of-the-nrf2-ho%C3%A2-1-pathway
#19
Yi Zhou, Jing Zhang, Biao Lei, Wenjin Liang, Jianhua Gong, Chuanxiang Zhao, Jidong Yu, Xuan Li, Bo Tang, Shengguang Yuan
Hepatic ischemia/reperfusion (I/R) injury is a common pathophysiological process that occurs following liver surgery, which is associated with oxidative stress, and can cause acute liver injury and lead to liver failure. Recently, the development of drugs for the prevention of hepatic I/R injury has garnered interest in the field of liver protection research. Previous studies have demonstrated that [D‑Ala2, D‑Leu5]‑Enkephalin (DADLE) exerts protective effects against hepatic I/R injury. To further clarify the specific mechanism underlying the effects of DADLE on hepatic I/R injury, the present study aimed to observe the effects of various doses of DADLE on hepatic I/R injury in mice...
August 29, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28900315/efficacy-and-safety-of-deferasirox-in-pediatric-patients-of-thalassemia-at-a-tertiary-care-teaching-hospital
#20
Dhaval R Thakor, Chetna K Desai, Jigar D Kapadia, Ram K Dikshit, K M Mehariya
OBJECTIVE: To evaluate efficacy, safety and utilization pattern of deferasirox in paediatric patients of transfusion dependant β Thalassemia Major at a tertiary care teaching hospital in Gujarat. MATERIALS AND METHODS: This observational, prospective-retrospective, single centre, continuous study was conducted in a tertiary care teaching hospital among paediatric patients of transfusion dependent β Thalassemia Major. Patients treated with deferasirox for not more than 12 weeks were enrolled...
April 2017: Indian Journal of Medical and Paediatric Oncology
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