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https://www.readbyqxmd.com/read/28090800/similar-familial-risk-in-multiple-sclerosis-subgroups
#1
Jie Song, Virginija Karrenbauer, Ali Manouchehrinia, Catarina Almqvist, Jan Hillert, Helga Westerlind
BACKGROUND: A subgroup of patients diagnosed with multiple sclerosis (MS) present with no oligoclonal bands (OCB) in the cerebrospinal fluid (CSF). Several studies report different clinical characteristics and genetic associations between the two groups. OBJECTIVE: To investigate whether the OCB negative subgroup has a distinct etiology from band positive MS. METHODS: Using nationwide registers to estimate familial risks, which reflect the genetic contribution of a disease...
January 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28089787/antituberculosis-drugs-reducing-efflux-increasing-activity
#2
REVIEW
Liliana Rodrigues, Tanya Parish, Meenakshi Balganesh, José A Ainsa
In mycobacteria, it was assumed that efflux pumps only had a marginal role in drug resistance. In recent years, owing to the need to find novel drugs against multidrug-resistant tuberculosis, it has become clear that efflux should not be ignored. Although efflux inhibitors have been very useful for characterizing in vitro the properties of efflux pumps, their usefulness in vivo is limited because of their toxicity. Alternatively, programs aimed at discovering novel drugs for treating tuberculosis should implement strategies to characterize efflux liability of candidate drugs...
January 12, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28088333/mitochondrial-uncoupling-in-cancer-cells-liabilities-and-opportunities
#3
REVIEW
Gyorgy Baffy
Acquisition of the endosymbiotic ancestor of mitochondria was a critical event in eukaryote evolution. Mitochondria offered an unparalleled source of metabolic energy through oxidative phosphorylation and allowed the development of multicellular life. However, as molecular oxygen had become the terminal electron acceptor in most eukaryotic cells, the electron transport chain proved to be the largest intracellular source of superoxide, contributing to macromolecular injury, aging, and cancer. Hence, the 'contract of endosymbiosis' represents a compromise between the possibilities and perils of multicellular life...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28088032/oral-cannabidiol-does-not-produce-a-signal-for-abuse-liability-in-frequent-marijuana-smokers
#4
Shanna Babalonis, Margaret Haney, Robert J Malcolm, Michelle R Lofwall, Victoria R Votaw, Steven Sparenborg, Sharon L Walsh
BACKGROUND: Cannabidiol (CBD) is a naturally occurring constituent of the marijuana plant. In the past few years, there has been great interest in the therapeutic effects of isolated CBD and it is currently being explored for numerous disease conditions (e.g., pain, epilepsy, cancer, various drug dependencies). However, CBD remains a Schedule I drug on the U.S. Controlled Substances Act (CSA). Despite its status, there are no well-controlled data available regarding its abuse liability...
December 14, 2016: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28079578/the-liability-of-a-glowing-reference
#5
Victoria I Smith, Sophia T Cisler, Ronald S Litman
No abstract text is available yet for this article.
January 11, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28078468/surgery-of-the-hallux-valgus-in-an-ambulatory-setting-a-liability-risk
#6
L Galois, J-M Serwier, A D Arashvand
INTRODUCTION: The primary objective of the study is to make an inventory of malpractice in hallux valgus surgery in an ambulatory setting and to identify the patient characteristics for a higher risk of malpractice. The secondary objective is creating a methodology for analyzing the medicolegal aspects of a surgery in day case comparing with hospitalization. MATERIALS AND METHODS: The database of the Branchet insurance company was used. A total of 11,000 claims for a period of 11 years (2002-2013) have been investigated...
January 11, 2017: European Journal of Orthopaedic Surgery & Traumatology: Orthopédie Traumatologie
https://www.readbyqxmd.com/read/28078403/-chief-surgeon-surgery-only-with-a-chief-surgeon-liability-in-cases-of-inadmissible-representation
#7
L Kuball, R Sailer, A Wienke
No abstract text is available yet for this article.
January 11, 2017: HNO
https://www.readbyqxmd.com/read/28077575/effector-attenuating-substitutions-that-maintain-antibody-stability-and-reduce-toxicity-in-mice
#8
Megan Lo, Hok Seon Kim, Raymond K Tong, Travis W Bainbridge, Jean-Michel Vernes, Yin Zhang, Yuwen Linda Lin, Shan Chung, Mark S Dennis, Y Joy Yu Zuchero, Ryan J Watts, Jessica A Couch, Y Gloria Meng, Jasvinder K Atwal, Randall J Brezski, Christoph Spiess, James A Ernst
The antibody Fc region regulates antibody cytotoxic activities and serum half-life. In a therapeutic context however, the cytotoxic effector function of an antibody is often not desirable and can create safety liabilities by activating native host immune defenses against cells expressing the receptor-antigens. Several amino acid changes in the Fc region have been reported to silence or reduce the effector function of antibodies. These earlier studies focused primarily on the interaction of human antibodies with human Fc-Gamma; receptors, and it remains largely unknown how such changes to the Fc might translate in the context of a murine antibody...
January 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28073688/state-legal-innovations-to-encourage-naloxone-dispensing
#9
Corey Davis, Derek Carr
OBJECTIVES: The opioid overdose epidemic continues to claim the lives of tens of thousands of Americans every year. Increased access to the opioid antagonist naloxone can reduce opioid-related morbidity and mortality. In this commentary, we describe several recent legal innovations designed to encourage pharmacists to ensure that naloxone is available when and where it is needed, and dispel some common misconceptions regarding potential legal risks associated with pharmacy naloxone dispensing...
January 7, 2017: Journal of the American Pharmacists Association: JAPhA
https://www.readbyqxmd.com/read/28070788/developmental-markers-of-genetic-liability-to-autism-in-parents-a-longitudinal-multigenerational-study
#10
Molly Losh, Gary E Martin, Michelle Lee, Jessica Klusek, John Sideris, Sheila Barron, Thomas Wassink
Genetic liability to autism spectrum disorder (ASD) can be expressed in unaffected relatives through subclinical, genetically meaningful traits, or endophenotypes. This study aimed to identify developmental endophenotypes in parents of individuals with ASD by examining parents' childhood academic development over the school-age period. A cohort of 139 parents of individuals with ASD were studied, along with their children with ASD and 28 controls. Parents' childhood records in the domains of language, reading, and math were studied from grades K-12...
January 9, 2017: Journal of Autism and Developmental Disorders
https://www.readbyqxmd.com/read/28070621/behavioral-evidence-for-the-abuse-potential-of-the-novel-synthetic-cathinone-alpha-pyrrolidinopentiothiophenone-pvt-in-rodents
#11
Jae Hoon Cheong, Mee Jung Choi, Choon-Gon Jang, Yong Sup Lee, Sooyeun Lee, Hee Jin Kim, Joung-Wook Seo, Seong Shoon Yoon
RATIONALE: Synthetic cathinones are chemical derivatives of cathinone that are pharmacologically similar to cocaine and methamphetamine. Recently, abuse of synthetic cathinones among young people has increased. OBJECTIVES: The present study aimed to characterize the behavioral effects of alpha-pyrrolidinopentiothiophenone (PVT), an analog of alpha-pyrrolidinovalerophenone and second-generation synthetic cathinone, as well as to evaluate its abuse potential, using conditioned place preference, intravenous self-administration (SA), and drug discrimination paradigms in rodent models...
January 9, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28069985/high-throughput-imaging-of-cardiac-microtissues-for-the-assessment-of-cardiac-contraction-during-drug-discovery
#12
Amy Pointon, James Pilling, Thierry Dorval, Yinhai Wang, Caroline Archer, Christopher Pollard
Cardiotoxicity is a common cause of attrition in preclinical and clinical drug development. Current in vitro approaches have two main limitations, they either are limited to low throughput methods not amendable to drug discovery or lack the physiological responses to allow an integrated risk assessment. A human 3D cardiac microtissue containing human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), cardiac endothelial cells and cardiac fibroblast were used to assess their suitability to detect drug induced changes in cardiomyocyte contraction...
November 15, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28066147/prediction-of-pharmacokinetics-and-drug-drug-interaction-potential-using-physiologically-based-pharmacokinetic-pbpk-modeling-approach-a-case-study-of-caffeine-and-ciprofloxacin
#13
Min-Ho Park, Seok-Ho Shin, Jin-Ju Byeon, Gwan-Ho Lee, Byung-Yong Yu, Young G Shin
Over the last decade, physiologically based pharmacokinetics (PBPK) application has been extended significantly not only to predicting preclinical/human PK but also to evaluating the drug-drug interaction (DDI) liability at the drug discovery or development stage. Herein, we describe a case study to illustrate the use of PBPK approach in predicting human PK as well as DDI using in silico, in vivo and in vitro derived parameters. This case was composed of five steps such as: simulation, verification, understanding of parameter sensitivity, optimization of the parameter and final evaluation...
January 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28062532/lipid-synthesis-is-a-metabolic-liability-of-non-small-cell-lung-cancer
#14
Robert U Svensson, Reuben J Shaw
The renaissance in the study of cancer metabolism has refocused efforts to identify and target metabolic dependencies of tumors as an approach for cancer therapy. One of the unique metabolic requirements that cancer cells possess to sustain their biosynthetic growth demands is altered fatty acid metabolism, in particular the synthesis of de novo fatty acids that are required as cellular building blocks to support cell division. Enhanced fatty acid synthesis that is observed in many tumor types has been postulated to open a therapeutic window for cancer therapy and, correspondingly, efforts to pharmacologically inhibit key enzymes of fatty acid synthesis are being pursued...
January 6, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28062017/non-invasive-prenatal-testing-and-the-unveiling-of-an-impaired-translation-process
#15
Blake Murdoch, Vardit Ravitsky, Ubaka Ogbogu, Sarah Ali-Khan, Gabrielle Bertier, Stanislav Birko, Tania Bubela, Jeremy De Beer, Charles Dupras, Meika Ellis, Palmira Granados Moreno, Yann Joly, Kalina Kamenova, Zubin Master, Alessandro Marcon, Mike Paulden, François Rousseau, Timothy Caulfield
Non-invasive prenatal testing (NIPT) is an exciting technology with the potential to provide a variety of clinical benefits, including a reduction in miscarriages, via a decline in invasive testing. However, there is also concern that the economic and near-future clinical benefits of NIPT have been overstated and the potential limitations and harms underplayed. NIPT, therefore, presents an opportunity to explore the ways in which a range of social pressures and policies can influence the translation, implementation, and use of a health care innovation...
January 2017: Journal of Obstetrics and Gynaecology Canada: JOGC, Journal D'obstétrique et Gynécologie du Canada: JOGC
https://www.readbyqxmd.com/read/28059434/assessment-of-abuse-liability-of-tramadol-among-experienced-drug-users-double-blind-crossover-randomized-controlled-trial
#16
Mrinmay Das, Raka Jain, Anju Dhawan, Amandeep Kaur
BACKGROUND: Tramadol is a widely used opioid analgesic. Different preclinical, clinical, and postmarketing surveillance studies show conflicting results regarding abuse potential of this drug. METHODS: A randomized double-blind complete crossover study was conducted at National Drug Dependence Treatment Centre, All India Institute of Medical Sciences, New Delhi. Total subjects were 10, comprising total 120 observations (each subject assessed at baseline, 5, 45, and 240 minutes)...
November 2016: Journal of Opioid Management
https://www.readbyqxmd.com/read/28057524/involvement-of-presynaptic-5-ht1a-receptors-in-the-low-propensity-of-brexpiprazole-to-induce-extrapyramidal-side-effects-in-rats
#17
Cedric Mombereau, Jørn Arnt, Arne Mørk
Previous studies have shown that partial and full 5-HT1A receptor agonists reduce antipsychotic-induced catalepsy. Consequently, some antipsychotics combining balanced efficacy between dopamine (DA) D2 antagonism or partial agonism and 5-HT1A receptor agonism have a low propensity to induce extrapyramidal side effects (EPS), as reflected by low cataleptogenic activity in rodents. In the present experiments, we attempted to explore the importance of pre- and postsynaptic 5-HT1A agonistic properties of brexpiprazole and aripiprazole in the context of neurological side-effect liabilities...
January 3, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28057475/motivation-emotion-regulation-and-the-latent-structure-of-psychopathology-an-integrative-and-convergent-historical-perspective
#18
Theodore P Beauchaine, Aimee Zisner
Motivational models of psychopathology have long been advanced by psychophysiologists, and have provided key insights into neurobiological mechanisms of a wide range of psychiatric disorders. These accounts emphasize individual differences in activity and reactivity of bottom-up, subcortical neural systems of approach and avoidance in affecting behavior. Largely independent literatures emphasize the roles of top-down, cortical deficits in emotion regulation and executive function in conferring vulnerability to psychopathology...
January 3, 2017: International Journal of Psychophysiology
https://www.readbyqxmd.com/read/28057325/design-synthesis-and-biological-screening-of-some-novel-celecoxib-and-etoricoxib-analogs-with-promising-cox-2-selectivity-anti-inflammatory-activity-and-gastric-safety-profile
#19
Shahinda S R Alsayed, Heba A H Elshemy, Mohamed A Abdelgawad, Mahmoud S Abdel-Latif, Khaled R A Abdellatif
Two new series of 4,6-diaryl-3-cyanopyridine 4a-r and 1,3,5-triaryl-2-pyrazolines 6a-f and were prepared. The new compounds were evaluated for their in vitro COX-2 selectivity and in vivo anti-inflammatory activity. Compounds 4o,r and 6d,f had moderate to high selectivity index (S.I.) compared to celecoxib (selectivity indexes of 4.5, 3.14, 4.79 and 3.21, respectively) and also, showed in vivo anti-inflammatory activity approximately equal to or higher than celecoxib (edema inhibition %=60.5, 64.5, 59.3 and 59...
December 26, 2016: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28053157/blockade-of-protease-activated-receptor-4-par4-provides-robust-antithrombotic-activity-with-low-bleeding
#20
Pancras C Wong, Dietmar Seiffert, J Eileen Bird, Carol A Watson, Jeffrey S Bostwick, Mary Giancarli, Nick Allegretto, Ji Hua, David Harden, Jocelyne Guay, Mario Callejo, Michael M Miller, R Michael Lawrence, Jacques Banville, Julia Guy, Brad D Maxwell, E Scott Priestley, Anne Marinier, Ruth R Wexler, Michel Bouvier, David A Gordon, William A Schumacher, Jing Yang
Antiplatelet agents are proven efficacious treatments for cardiovascular and cerebrovascular diseases. However, the existing drugs are compromised by unwanted and sometimes life-threatening bleeding that limits drug usage or dosage. There is a substantial unmet medical need for an antiplatelet drug with strong efficacy and low bleeding risk. Thrombin is a potent platelet agonist that directly induces platelet activation via the G protein (heterotrimeric guanine nucleotide-binding protein)-coupled protease-activated receptors PAR1 and PAR4...
January 4, 2017: Science Translational Medicine
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