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Jaime Ibarrola, Rafael Sádaba, Amaia Garcia-Peña, Vanessa Arrieta, Ernesto Martinez-Martinez, Virginia Alvarez, Amaya Fernández-Celis, Alicia Gainza, Enrique Santamaría, Joaquin Fernández-Irigoyen, Victoria Cachofeiro, Renaud Fay, Patrick Rossignol, Natalia López-Andrés
AIMS: Galectin-3 (Gal-3), a β-galactoside-binding lectin involved in cardiac inflammation and fibrosis, could regulate oxidative stress, although the mechanisms have not been elucidated. We herein investigated the changes in oxidative stress-related mediators induced by Gal-3 in human cardiac fibroblasts and in pathological animal and human models of cardiac diseases. RESULTS: Using quantitative proteomics and immunodetection approaches, we have identified that Gal-3 down-regulated fumarate hydratase (FH) in human cardiac fibroblasts...
May 1, 2018: International Journal of Cardiology
Patrick Darken, Paolo DePetrillo, Colin Reisner, Earl St Rose, Paul Dorinsky
The budesonide/glycopyrronium/formoterol fumarate dihydrate metered dose inhaler (BGF MDI) is an inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2 -agonist fixed-dose combination formulated with innovative co-suspension delivery technology that is in clinical development for the treatment of chronic obstructive pulmonary disease (COPD). This randomized, Phase I, single-dose, six-treatment, four-period, crossover study (NCT01980615) examined the pharmacokinetic (PK) and safety profile of three doses of BGF MDI (320/14...
March 12, 2018: Pulmonary Pharmacology & Therapeutics
Michela Semeraro, Sara Boenzi, Rosalba Carrozzo, Daria Diodato, Diego Martinelli, Giorgia Olivieri, Giacomo Antonetti, Elisa Sacchetti, Giulio Catesini, Cristiano Rizzo, Carlo Dionisi-Vici
Single large-scale mitochondrial DNA deletions disorders are classified into three main phenotypes with frequent clinical overlap: Pearson marrow-pancreas syndrome (PMS), Kearns-Sayre syndrome (KSS) and chronic progressive external ophtalmoplegia (PEO). So far, only few anecdotal studies have reported on the urinary organic acids profile in this disease class. In this single-center retrospective study, we performed quantitative evaluation of urinary organic acids in a series of 15 pediatric patients, 7 with PMS and 8 with KSS...
March 10, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Loraine Van Slyke, Mia Scott
HIV pre-exposure prophylaxis (PrEP) with emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) fixed-dose combination (FTC/TDF) is undergoing rapid scale-up in the United States. While FTC/TDF is typically well tolerated, to our knowledge, cranial nerve pathology associated with FTC/TDF has not been previously described. We report the case of a 35-year-old patient who began FTC/TDF PrEP and developed acute trigeminal neuralgia. The neurologic symptoms resolved after treatment discontinuation and recurred upon rechallenge, resulting in permanent discontinuation of PrEP treatment...
January 2018: Journal of the International Association of Providers of AIDS Care
Mst Ishrat Jahan, Ryuta Tobe, Hisaaki Mihara
The extI gene in Geobacter sulfurreducens encodes a putative outer membrane channel porin, which resides within a cluster of extHIJKLMNOPQS genes. This cluster is highly conserved across the Geobacteraceae and includes multiple putative c -type cytochromes. In silico analyses of the ExtI sequence, together with Western blot analysis and proteinase protection assays, showed that it is an outer membrane protein. The expression level of ExtI did not respond to changes in osmolality and phosphate starvation. An extI -deficient mutant did not show any significant impact on fumarate or Fe(III) citrate reduction or sensitivity to β-lactam antibiotics, as compared with those of the wild-type strain...
March 11, 2018: International Journal of Molecular Sciences
Magali Ranchou-Peyruse, Marisol Goñi-Urriza, Marion Guignard, Marjorie Goas, Anthony Ranchou-Peyruse, Rémy Guyoneaud
The strain BerOc1T was isolated from brackish sediments contaminated with hydrocarbons and heavy metals. This strain has been used as a model strain of sulfate-reducer to study the biomethylation of mercury. The cells are vibrio-shaped, motile and not sporulated. Phylogeny and physiological traits placed this strain within the genus Pseudodesulfovibrio. Optimal growth was obtained at 30 °C, 1.5 % NaCl and pH 6.0-7.4. The estimated G+C content of the genomic DNA was 62.6 mol%. BerOc1T used lactate, pyruvate, fumarate, ethanol and hydrogen...
March 13, 2018: International Journal of Systematic and Evolutionary Microbiology
Bárbara Piñeiro, Diana R Díaz, Luis M Monsalve, Úrsula Martínez, Cathy D Meade, Lauren R Meltzer, Karen O Brandon, Marina Unrod, Thomas H Brandon, Vani N Simmons
Smoking-related illnesses are the leading causes of death among Hispanics/Latinos. Yet, there are few smoking cessation interventions targeted for this population. The goal of this study was to "transcreate" an existing, previously validated, English language self-help smoking cessation intervention, titled Forever Free® : Stop Smoking for Good, for Spanish-speaking smokers. Rather than simply translating the materials, our transcreation process involved culturally adapting the intervention to enhance acceptability and receptivity of the information...
March 13, 2018: Journal of Health Communication
Cynthuja Thilakanathan, Gabrielle Wark, Michael Maley, Scott Davison, Joseph Lawler, Aimei Lee, Nicholas Shackel, Vi Nguyen, Kathy Jackson, Anne Glass, Stephen A Locarnini, Miriam T Levy
BACKGROUND/AIMS: Anti-partum antiviral therapy in the setting of high viral load is recommended to prevent mother-to-child transmission of hepatitis B although recommended viral load cut-offs vary. Quantitative HBsAg has been proposed as an alternative screening strategy to identify high viral load in this setting. Guidelines suggest testing all infants for vaccine response and infection. We set out to re-examine viral load cut-offs; the predictive value of quantitative HBsAg and the need for follow-up infant testing in our cohort...
March 12, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
George Vavougios, Sotirios G Zarogiannis, Triantafylos Doskas
Recent research has outlined that Dimethyl Fumarate (DMF) functions as a gene regulator via multiple pathways, critical among which is the NRF2 cytoprotective cascade. PARK7/DJ-1 is a multifunctional protein that acts as a redox sensor and effector of multiple cytoprotective pathways, including NRF2. Specifically, it prevents the association of NRF2 with its inhibitor KEAP1, allowing NRF2 to enter the nucleus and mediate cytoprotective and antioxidant cascades. It is our hypothesis that while the NRF2-KEAP1 inhibitory complex is reported the main pharmacological target for DMF's NRF dependent functions, no study to date has explored the effects of DMF on DJ-1's expression, and vice-versa, the possibility of a regulatory inadequacy in the upstream, oxidant-responsive DJ-1 activator of the NRF2 cascade...
February 26, 2018: Multiple Sclerosis and related Disorders
Monica Gandhi, Rajesh T Gandhi, Andrei Stefanescu, Ronald J Bosch, Joshua C Cyktor, Howard Horng, Alexander Louie, Nhi Phung, Joseph J Eron, Evelyn Hogg, Bernard J C Macatangay, Christopher Hensel, Courtney V Fletcher, John W Mellors, Deborah K McMahon
Data on the relationship of antiretroviral exposure to measures of human immunodeficiency virus (HIV) persistence are limited. To address this gap, multiple viral, immunologic, and pharmacologic measures were analyzed from individuals with sustained virologic suppression on therapy (median 7 years) in the AIDS Clinical Trials Group A5321 cohort. Among 110 participants on tenofovir-(TFV)-disoproxil-fumarate (TDF)/emtricitabine (FTC)-containing regimens, we found no significant correlation between hair concentrations of individual antiretrovirals (ARVs) in the regimen and measures of HIV persistence (plasma HIV-1 RNA by single copy assay, cell-associated-DNA, cell-associated RNA) or soluble markers of inflammation...
February 26, 2018: Journal of Infectious Diseases
Muge Cevik, Chloe Orkin
PURPOSE OF REVIEW: In an era when virological efficacy approaches 100%, novel antiretroviral (ARV) therapies must deliver better tolerability, safety, and convenient coformulated regimens. We review the phase II and III clinical data on the fixed dose combination (FDC) darunavir (DRV) 800mg / cobicistat (COBI/C) 150 mg / emtricitabine (F/FTC) 200 mg / tenofovir alafenamide fumarate (TAF) 10mg (D/C/F/TAF) for the treatment of HIV-1 infection. RECENT FINDINGS: In an exploratory phase II study, D/C/F/TAF FDC demonstrated similar virological efficacy to darunavir/cobicistat FDC + F /tenofovir disoproxil fumarate (TDF) FDC in treatment-naive HIV-1-infected individuals with favorable bone and renal outcomes...
March 9, 2018: Current Opinion in HIV and AIDS
Gunjan Gupta, Rahul Sudan, Sabha Mushtaq
Cutaneous leiomyomas (CLs) are uncommon benign smooth muscle tumours characterised by solitary or multiple painful nodules. Based on origin, three types are recognised, namely piloleiomyoma, dartoic leiomyoma, and angioleiomyoma, with piloleiomyomas being the commonest one. Reed's syndrome also known as multiple cutaneous and uterine leiomyomatosis (MCULs) is characterised by CLs in men and CLs and uterine fibroids in women. Association of Reed's syndrome with renal cell carcinoma is labelled as hereditary leiomyomatosis and renal cell carcinoma (HLRCC)...
January 2018: Indian Journal of Dermatology
Yeji Sung, Konstantina Spagou, Marina Kafeza, Michael Kyriakides, Brahman Dharmarajah, Joseph Shalhoub, Jose A Diaz, Thomas W Wakefield, Elaine Holmes, Alun H Davies
OBJECTIVES: Deep vein thrombosis (DVT) is a major health problem, responsible for significant morbidity and mortality. The identification of a simple and effective diagnostic biomarker of DVT remains a challenge. Metabolomics have recently emerged as a new powerful scientific tool to characterise metabolic phenotypes of complex diseases and investigate small molecules in biofluids. The aim of the study was to identify the blood and vein wall metabolomic signature of DVT in a murine experimental model...
March 8, 2018: European Journal of Vascular and Endovascular Surgery
Sara Shahbazi, Ali Zamanian, Mohammad Pazouki, Yaser Jafari
A new total biomimetic technique based on both the water uptake and degradation processes is introduced in this study to provide an interesting procedure to fabricate a bioactive and biodegradable synthetic scaffold, which has a good mechanical and structural properties. The optimization of effective parameters to scaffold fabrication was done by response surface methodology/central composite design (CCD). With this method, a synthetic scaffold was fabricated which has a uniform and open-interconnected porous structure with the largest pore size of 100-200μm...
May 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
Stanley L Cohan, Harold Moses, Jonathan Calkwood, Carlo Tornatore, Chris LaGanke, Kyle E Smoot, Venkata Meka, Macaulay Okwuokenye, Christophe Hotermans, Jason P Mendoza, Monica K Mann, Leslie A Meltzer
BACKGROUND: Delayed-release dimethyl fumarate (DMF) may be a therapeutic option for patients with relapsing-remitting multiple sclerosis (RRMS) who are treated with natalizumab and require a change in therapy. However, there is limited information regarding predictors of favorable treatment outcomes in patients switching from natalizumab to DMF. Clinical practices and sequencing protocols vary. Herein, we present the clinical results, including annualized relapse rate (ARR) and risk of relapse, of a phase 4 retrospective observational study of patients with RRMS who switched from natalizumab to DMF in a community practice setting (STRATEGY)...
February 26, 2018: Multiple Sclerosis and related Disorders
Mariko Kita, Robert J Fox, Ralf Gold, Gavin Giovannoni, J Theodore Phillips, Sujata P Sarda, Jessica Kong, Vissia Viglietta, Sarah I Sheikh, Macaulay Okwuokenye, Ludwig Kappos
No abstract text is available yet for this article.
March 7, 2018: Clinical Therapeutics
Erik Mogalian, Luisa M Stamm, Anu Osinusi, Diana M Brainard, Gong Shen, Kah Hiing John Ling, Anita Mathias
Background: Combining antiviral regimens in the HCV/HIV coinfected population can be complex as they share overlapping mechanisms for elimination that may result in potential drug interactions. The pharmacokinetics, safety, and tolerability of concomitantly administered sofosbuvir/velpatasvir (SOF/VEL) with multiple commonly prescribed antiretroviral (ARV) regimens were evaluated. Methods: Healthy volunteers were enrolled into two phase 1, open-label, randomized, multiple-dose, cross-over studies...
March 7, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Oliver Ciclet, Denis Barron, Steve Bajic, Jean-Luc Veuthey, Davy Guillarme, Alexandre Grand-Guillaume Perrenoud
The MS hyphenation performance of UniSpray®, a new design of atmospheric pressure ionization source was evaluated in both SFC and RPLC modes. Sensitivity, stability, versatility and matrix effects offered by the UniSpray were assessed in positive and negative ionization modes and systematically compared to an electrospray source (ESI) using 120 natural compounds covering an extended chemical space. In a first instance, a multivariate approach was used to screen and optimize the UniSpray source settings to maximize detection sensitivity...
March 5, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Cheng-Ju Kuo, Sin-Tian Wang, Chia-Mei Lin, Hao-Chieh Chiu, Cheng-Rung Huang, Der-Yen Lee, Geen-Dong Chang, Ting-Chen Chou, Jenn-Wei Chen, Chang-Shi Chen
The enteric pathogen enterohemorrhagic Escherichia coli (EHEC) is responsible for outbreaks of bloody diarrhea and hemolytic uremic syndrome (HUS) worldwide. Several molecular mechanisms have been described for the pathogenicity of EHEC; however, the role of bacterial metabolism in the virulence of EHEC during infection in vivo remains unclear. Here we show that aerobic metabolism plays an important role in the regulation of EHEC virulence in Caenorhabditis elegans. Our functional genomic analyses showed that disruption of the genes encoding the succinate dehydrogenase complex (Sdh) of EHEC, including the sdhA gene, attenuated its toxicity toward C...
March 7, 2018: Cell Death & Disease
Caiyun Fan, Di Su, He Tian, Xiaojiao Li, Yu Li, Lei Ran, Ruiting Hu, Jianbo Cheng
Objective: The objective of the present study was to elucidate the mechanism underlying liver metabolic perturbations in dairy cows exposed to heat stress (HS). Method: Liquid chromatography mass spectrometry (LC-MS) was used to analyze metabolic differences in livers of 20 dairy cows, with and without exposure to HS. Results: The results revealed 33 potential metabolite candidate biomarkers for the detection of HS in dairy cows. Fifteen of these metabolites (glucose, lactate, pyruvate, acetoacetate, β-hydroxybutyrate (BHBA), fumaric acid, citric acid, choline, glycine, proline, isoleucine, leucine, urea, creatinine, and orotic acid) were previously found to be potential biomarkers of HS in plasma or milk, discriminating dairy cows with and without HS...
March 2, 2018: Asian-Australasian Journal of Animal Sciences
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