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Farah Tamirou, Séverine Nieuwland Husson, Damien Gruson, Frédéric Debiève, Bernard R Lauwerys, Frédéric A Houssiau
OBJECTIVE: The low-dose intravenous (IV) cyclophosphamide (CY) Euro-Lupus (EL) regimen (cumulative dose of 3 g) was developped to reduce gonadal toxicity. To address the possibility of a marginal effect on the ovarian reserve, we measured serum anti-Müllerian hormone (AMH) titers in patients suffering from systemic lupus erythematosus (SLE) treated with the EL regimen and compared them to those measured in patients treated with higher doses of IVCY or never treated with IVCY. METHODS: Serum AMH levels were measured by ELISA in a cohort of 155 premenopausal SLE patients, of whom 30 had received the EL regimen and 24 higher doses of IVCY...
February 24, 2017: Arthritis & Rheumatology
N Moore, M Moreno Gonzales, K Bonner, B Smith, W Park, M Stegall
Plasma cells (PCs) are a major source of alloantibody in transplant patients and are resistant to current therapy. Since receptor/ligand interactions in stromal microenvironments play important roles in the localization, development and survival of normal PCs, we hypothesized that interfering with CXCR4/CXCL12 interactions with plerixafor might cause PC depletion and enhance the efficacy of the proteasome inhibitor, bortezomib. PCs in mouse spleen, bone marrow and peripheral blood demonstrated CXCR4 expression...
February 24, 2017: American Journal of Transplantation
Alisa Glukhova, David M Thal, Anh T Nguyen, Elizabeth A Vecchio, Manuela Jörg, Peter J Scammells, Lauren T May, Patrick M Sexton, Arthur Christopoulos
The adenosine A1 receptor (A1-AR) is a G-protein-coupled receptor that plays a vital role in cardiac, renal, and neuronal processes but remains poorly targeted by current drugs. We determined a 3.2 Å crystal structure of the A1-AR bound to the selective covalent antagonist, DU172, and identified striking differences to the previously solved adenosine A2A receptor (A2A-AR) structure. Mutational and computational analysis of A1-AR revealed a distinct conformation of the second extracellular loop and a wider extracellular cavity with a secondary binding pocket that can accommodate orthosteric and allosteric ligands...
February 23, 2017: Cell
Rômulo Pillon Barcelos, Guilherme Bresciani, Maria José Cuevas, Susana Martínez-Flórez, Félix Antunes A Soares, Javier González-Gallego
Non-steroidal anti-inflammatory drugs, such as diclofenac, are widely used to treat inflammation and pain in several conditions, including sports injuries. This study analyzes the influence of diclofenac on the TLR-NF-kB pathway in skeletal muscle of rats submitted to acute eccentric exercise. Twenty male Wistar rats were divided into four groups: control-saline, control-diclofenac, exercise-saline and exercise-diclofenac. Diclofenac or saline were administered for 7 days prior to an acute eccentric exercise bout...
February 24, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
Mazen Zaitouna, Bayan Alsaid, Cédric Lebacle, Krystel Nyangoh Timoh, Gérard Benoît, Thomas Bessede
AIMS: Innervation of the pelvic ureter traditionally comes from the pelvic plexus. This innervation is independent: adrenergic and cholinergic. The purpose of this study was to describe more precisely the origin and nature of its innervation (adrenergic, cholinergic, nitrergic, and somatic). METHODS: Six specimens of normal human fetal pelvis (four male and two female) from 20 to 30 weeks gestation were studied. The sections of these fetuses, carried out every 5 µm without interval, were treated with Hematoxylin Eosin (HE), with Masson's trichrome (TriM), immunolabeling of smooth muscle cells with smooth anti-actin, of nerves with anti-S100 protein, anti-tyrosine hydroxylase, anti-VAChT, anti-nNOS, and with anti- peripheral myelin protein 22 (PMP 22)...
February 2017: Neurourology and Urodynamics
Jan Schjøtt, Hilde Marie Torgauten, Tormod Karlsen Bjånes
Drug shortages occur frequently and they can affect patient safety [1-3]. Shortage involves medicines used in cancer, anaesthesia and in the treatment and prevention of chronic diseases and life-threatening conditions [1-3]. The potential for medication errors increases during drug shortages due to prescribing of unfamiliar agents [4]. This problem was highlighted with digitalis glycosides in Norway 2012. This article is protected by copyright. All rights reserved.
February 24, 2017: Basic & Clinical Pharmacology & Toxicology
Cory M Vela, Todd C Knepper, Nancy K Gillis, Christine M Walko, Howard L McLeod, J Kevin Hicks
INTRODUCTION: Moffitt Cancer Center's Personalized Medicine Clinical Service (PMCS) reviews somatic next-generation sequencing (NGS) assay results, provides interpretations, and identifies potential therapeutic options. The number of individuals reviewed by our clinical service who are eligible for on-label or off-label drug therapy based on genetic test results has previously not been quantitated. Herein, we determined the number of patients harboring an actionable mutation that would qualify a patient for an on-label drug or consideration for off-label drug treatment...
February 24, 2017: Pharmacotherapy
Jun Yin, Jian Zhao, Weimin Hu, Guangping Yang, Hui Yu, Ruihao Wang, Linjing Wang, Guoqian Zhang, Wenfan Fu, Lu Dai, Wanzhen Li, Boyu Liao, Shuxu Zhang
Radio- and chemo-resistance represent major obstacles in the therapy of non-small-cell lung cancer (NSCLC) and the underlying molecular mechanisms are not known. In the present study, during induction of radio- or chemo-resistance in NSCLC cells, dynamic analyses revealed that decreased expression of let-7 induced by irradiation or cisplatin resulted in increased expression of its target gene LIN28, and increased expression of LIN28 then contributed to further decreased expression of let-7 by inhibiting its maturation and biogenesis...
2017: PloS One
Paul S Stadem, Megan V Hilgers, Derrick Bengo, Sarah E Cusick, Susan Ndidde, Tina M Slusher, Troy C Lund
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disorder that affects as many as 400 million people worldwide, making it the most common enzymatic defect. Subjects with G6PD deficiency are more likely to develop neonatal hyperbilirubinemia potentially leading to kernicterus and are at increased risk for acute hemolytic anemia when exposed to pro-oxidant compounds such as anti-malarial drugs. We collected umbilical cord blood from 300 males born in Uganda to assess for novel markers of systemic oxidative stress...
2017: PloS One
Maureen J Kimulwo, Javan Okendo, Rashid A Aman, Bernhards R Ogutu, Gilbert O Kokwaro, Dorothy J Ochieng, Anne W T Muigai, Florence A Oloo, Washingtone Ochieng
Treatment failure is a key challenge in the management of HIV-1 infection. We conducted a mixed-model survey of plasma nevirapine (NVP) concentrations (cNVP) and viral load in order to examine associations with treatment and adherence outcomes among Kenyan patients on prolonged antiretroviral therapy (ART). Blood plasma was collected at 1, 4 and 24 hours post-ART dosing from 58 subjects receiving NVP-containing ART and used to determine cNVP and viral load (VL). Median duration of treatment was 42 (range, 12-156) months, and 25 (43...
2017: PloS One
Johannes P Mouton, Ushma Mehta, Dawn P Rossiter, Gary Maartens, Karen Cohen
INTRODUCTION: A new method to assess causality of suspected adverse drug reactions, the Liverpool Adverse Drug Reaction Causality Assessment Tool (LCAT), showed high interrater agreement when used by its developers. Our aim was to compare the interrater agreement achieved by LCAT to that achieved by another causality assessment method, the World Health Organization-Uppsala Monitoring Centre system for standardised case causality assessment (WHO-UMC system), in our setting. METHODS: Four raters independently assessed adverse drug reaction causality of 48 drug-event pairs, identified during a hospital-based survey...
2017: PloS One
Godfather Dickson Kimaro, Sayoki Mfinanga, Victoria Simms, Sokoine Kivuyo, Christian Bottomley, Neil Hawkins, Thomas S Harrison, Shabbar Jaffar, Lorna Guinness
BACKGROUND: Understanding the costs associated with health care delivery strategies is essential for planning. There are few data on health service resources used by patients and their associated costs within antiretroviral (ART) programmes in Africa. MATERIAL AND METHODS: The study was nested within a large trial, which evaluated screening for cryptococcal meningitis and tuberculosis and a short initial period of home-based adherence support for patients initiating ART with advanced HIV disease in Tanzania and Zambia...
2017: PloS One
Miłosz Parczewski, Magdalena Leszczyszyn-Pynka, Magdalena Witak-Jędra, Bartosz Szetela, Jacek Gąsiorowski, Brygida Knysz, Monika Bociąga-Jasik, Paweł Skwara, Anna Grzeszczuk, Maria Jankowska, Grażyna Barałkiewicz, Iwona Mozer-Lisewska, Władysław Łojewski, Katarzyna Kozieł, Edyta Grąbczewska, Elżbieta Jabłonowska, Anna Urbańska
INTRODUCTION: Reconstruction of HIV transmission links allows to trace the spread and dynamics of infection and guide epidemiological interventions. The aim of this study was to characterize transmission networks among subtype B infected patients from Poland. MATERIAL AND METHODS: Maximum likelihood phylogenenetic trees were inferred from 966 HIV-1 subtype B protease/reverse transcriptase sequences from patients followed up in nine Polish HIV centers. Monophyletic clusters were identified using 3% within-cluster distance and 0...
2017: PloS One
Arwa Kurabi, Kerry A Beasley, Lisa Chang, James McCann, Kwang Pak, Allen F Ryan
Otitis media (OM) is the most common infectious disease of children under six, causing more antibiotic prescriptions and surgical procedures than any other pediatric condition. By screening a bacteriophage (phage) library genetically engineered to express random peptides on their surfaces, we discovered unique peptides that actively transport phage particles across the intact tympanic membrane (TM) and into the middle ear (ME). Herein our goals were to characterize the physiochemical peptide features that may underlie trans-TM phage transport; assess morphological and functional effects of phage peptides on the ME and inner ear (IE); and determine whether peptide-bearing phage transmigrate from the ME into the IE...
2017: PloS One
Yuko Yamada, Masakatsu Takanashi, Katsuko Sudo, Shinobu Ueda, Shin-Ichiro Ohno, Masahiko Kuroda
MicroRNA 29b (miR-29b) replacement therapy is effective for suppressing fibrosis in a mouse model. However, to develop clinical applications for miRNA mimics, the side effects of nucleic acid drugs have to be addressed. In this study, we focused on miRNA mimics in order to develop therapies for idiopathic pulmonary fibrosis. We developed a single-stranded RNA, termed "miR-29b Psh-match," that has a unique structure to avoid problems associated with the therapeutic uses of miRNAs. A comparison of miR-29b Psh-match and double-stranded one, termed "miR-29b mimic" indicated that the single-stranded form was significantly effective towards fibrosis according to both in vivo and in vitro experiments...
2017: PloS One
Stéphane Bermon
PURPOSE OF REVIEW: During the last decades androgens have been used illicitly by athletes of both genders. Because of some obvious ethical limitations, mechanisms underlying the performance-enhancing effects of these hormone or drugs, as well as the magnitude of their effects, have been poorly addressed. This review aims to combine findings from field and from the laboratory to provide new insights into the ergogenic properties of endogenous or exogenous androgens on female athletes. RECENT FINDINGS: Results obtained from recent neuropsychological studies indicated that testosterone, and not the sex chromosomes, is responsible for the sexual differentiation of visuospatial neural activation...
February 23, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
Hunter B Moore, Robert D Winfield, Mayuki Aibiki, Matthew D Neal
Coagulopathy is a common and vexing clinical problem in critically ill patients. Recently, major advances focused on the treatment of coagulopathy in trauma and sepsis have emerged. However, the targeting of coagulopathy with blood product transfusion and drugs directed at attenuating the physiologic response to these conditions have major potential risk to the patient. Therefore, the identification of coagulopathy as a clinical target is an area of uncertainty and controversy. In order to analyze the state of the science regarding coagulopathy in critical illness, a symposium addressing the problem was organized at the 39 annual meeting of the Shock Society in the summer of 2016...
February 23, 2017: Shock
Harshvardhan Rao, Neeraj Gaur, Dnyanesh Tipre
Diabetic neuropathies (DNs) are nerve-damaging disorders associated with diabetes. They are commonly attributed to peripheral nerves and primarily affect the limbs of the patient. They cause altered sensitivity to external stimuli along with loss in balance and reflexes of the affected patient. DNs are associated with a variety of clinical manifestations including autonomic failure and are caused by poor management of blood sugar levels. Imaging modalities provide vital information about early physiological changes in DNs...
February 23, 2017: Nuclear Medicine Communications
Eric G Meissner
PURPOSE OF REVIEW: Availability of direct acting antivirals (DAAs) that demonstrate remarkable clinical efficacy and safety has revolutionized the ability to treat chronic infection with hepatitis C virus (HCV). An equal measure of clinical success has now been achieved in persons coinfected with HCV and the HIV, a historically harder to cure cohort with interferon-based therapy. Global goals include identifying all HIV-HCV-infected persons, gaining access to DAA therapy, preventing de novo and reinfection, and managing the sequelae of chronic infection...
February 23, 2017: Current Opinion in Gastroenterology
Deliana Kostova, Jared Fox
BACKGROUND: Prescription drug copayments and cost-sharing have been linked to reductions in prescription drug use and expenditures. However, little is known about their effect on specific health outcomes. OBJECTIVE: To evaluate the association between prescription drug copayments and uncontrolled hypertension, uncontrolled hypercholesterolemia, and prescription drug utilization among Medicaid beneficiaries with these conditions. SUBJECTS: Select adults aged 20-64 from NHANES 1999-2012 in 18 states...
February 23, 2017: Medical Care
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