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https://www.readbyqxmd.com/read/28819003/skeletal-muscle-signaling-metabolism-and-performance-during-sprint-exercise-in-severe-acute-hypoxia-after-the-ingestion-of-antioxidants
#1
David Morales-Alamo, Borja Guerra, Jesus Gustavo Ponce-Gonzalez, Amelia Guadalupe-Grau, Alfredo Santana, Marcos Martin-Rincon, Miriam Gelabert-Rebato, Joan Aureli Cadefau, Roser Cussó, Cecilia Dorado, Jose A L Calbet
The aim of this study was to determine reactive oxygen species (ROS) could play a role in blunting Thr(172)-AMPKα phosphorylation in human skeletal muscle after sprint exercise in hypoxia and to elucidate the potential signaling mechanisms responsible for this response. Nine volunteers performed a single 30s sprint (Wingate test) in two occasions while breathing hypoxic gas (PIO2=75 mmHg): one after the ingestion of placebo (P) and another following the intake of antioxidants (A) (α-lipoic acid, vitamin C, and vitamin E), with a randomized double-blind design...
August 17, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28818050/administration-of-two-probiotic-strains-during-early-childhood-does-not-affect-the-endogenous-gut-microbiota-composition-despite-probiotic-proliferation
#2
Martin Frederik Laursen, Rikke Pilmann Laursen, Anni Larnkjær, Kim F Michaelsen, Martin Iain Bahl, Tine Rask Licht
BACKGROUND: Probiotics are increasingly applied to prevent and treat a range of infectious, immune related and gastrointestinal diseases. Despite this, the mechanisms behind the putative effects of probiotics are poorly understood. One of the suggested modes of probiotic action is modulation of the endogenous gut microbiota, however probiotic intervention studies in adults have failed to show significant effects on gut microbiota composition. The gut microbiota of young children is known to be unstable and more responsive to external factors than that of adults...
August 17, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28816293/-effects-of-bioactive-glass-on-reducing-the-hypersensitivity-after-full-crown-preparation
#3
H Li, Y H Liu, Z Q Luo
OBJECTIVE: To evaluate the efficacy of the 45S5 bioactive glass on the reduction of hypersensitivity of teeth prepared for full coverage crowns. METHODS: In the study, 31 prepared abutment teeth with vital pulp from 18 patients satisfied the inclusion criteria and exclusion criteria. The patients were informed consent and recruited into the study. This was a before and after self-control, single blind clinical trial. The severity of tooth hypersensitivity at baseline was evaluated, after application of the placebo, which was the powder of zinc oxide, and after application of the 45S5 bioactive glass on the same tooth...
August 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28815639/safety-tolerability-and-pharmacokinetic-characteristics-of%C3%A2-a-novel-nonopioid-analgesic-vvz-149-injections-in-healthy-volunteers-a-first-in-class-first-in-human-study
#4
Jaeseong Oh, SeungHwan Lee, Anhye Kim, Jangsoo Yoon, Kyungho Jang, Doo H Lee, Sunyoung Cho, Sang Rim Lee, Kyung-Sang Yu, Jae-Yong Chung
VVZ-149, a dual antagonist of GlyT2 and 5HT2 A receptors, is an investigational analgesic with a novel mechanism of action that is currently under early-stage clinical development as an injectable agent for the treatment of postoperative pain. Here, the safety, tolerability, and pharmacokinetics of VVZ-149 injections in healthy male volunteers were explored in a randomized, double-blind, single- and multiple-ascending-dose (SAD and MAD, respectively), placebo-controlled clinical study. Subjects randomly received a 4-hour intravenous infusion of 0...
August 16, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28812048/sensorimotor-rhythm-neurofeedback-as-adjunct-therapy-for-parkinson-s-disease
#5
Ingrid H C H M Philippens, Jacqueline A Wubben, Raymond A P Vanwersch, Dave L Estevao, Peter A Tass
Neurofeedback may enhance compensatory brain mechanisms. EEG-based sensorimotor rhythm neurofeedback training was suggested to be beneficial in Parkinson's disease. In a placebo-controlled study in parkinsonian nonhuman primates we here show that sensorimotor rhythm neurofeedback training reduces MPTP-induced parkinsonian symptoms and both ON and OFF scores during classical L-DOPA treatment. Our findings encourage further development of sensorimotor rhythm neurofeedback training as adjunct therapy for Parkinson's disease which might help reduce L-DOPA-induced side effects...
August 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28810844/effect-of-tolvaptan-on-renal-handling-of-water-and-sodium-gfr-and-central-hemodynamics-in-autosomal-dominant-polycystic-kidney-disease-during-inhibition-of-the-nitric-oxide-system-a-randomized-placebo-controlled-double-blind-crossover-study
#6
Safa Al Therwani, My Emma Sofie Malmberg, Jeppe Bakkestroem Rosenbaek, Jesper Noergaard Bech, Erling Bjerregaard Pedersen
BACKGROUND: Tolvaptan slows progression of autosomal dominant polycystic kidney disease (ADPKD) by antagonizing the vasopressin-cAMP axis. Nitric oxide (NO) stimulates natriuresis and diuresis, but its role is unknown during tolvaptan treatment in ADPKD. METHODS: Eighteen patients with ADPKD received tolvaptan 60 mg or placebo in a randomized, placebo-controlled, double blind, crossover study. L-NMMA (L-NG-monomethyl-arginine) was given as a bolus followed by continuous infusion during 60 min...
August 15, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28809926/impact-of-fortified-versus-unfortified-lipid-based-supplements-on-morbidity-and-nutritional-status-a-randomised-double-blind-placebo-controlled-trial-in-ill-gambian-children
#7
Stefan A Unger, Saikou Drammeh, Jahid Hasan, Kabiru Ceesay, Edrisa Sinjanka, Sainey Beyai, Bakary Sonko, Bai Lamin Dondeh, Anthony J Fulford, Sophie E Moore, Andrew M Prentice
BACKGROUND: Multiple micronutrients (MMN) are commonly prescribed in pediatric primary healthcare in sub-Saharan Africa to improve nutritional status and appetite without evidence for their effectiveness or international clinical guidelines. Community-wide MMN supplementation has shown limited and heterogeneous impact on growth and morbidity. Short-term ready-to-use therapeutic foods in acutely sick children in a hospital setting also had limited efficacy regarding subsequent growth. The effectiveness of MMN in improving morbidity or growth in sick children presenting for primary care has not been assessed...
August 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28807037/selepressin-a-novel-selective-vasopressin-v1a-agonist-is-an-effective-substitute-for-norepinephrine-in-a-phase-iia-randomized-placebo-controlled-trial-in-septic-shock-patients
#8
James A Russell, Jean-Louis Vincent, Anne Louise Kjølbye, Håkan Olsson, Allan Blemings, Herbert Spapen, Peder Carl, Pierre-Francois Laterre, Lars Grundemar
BACKGROUND: Vasopressin is widely used for vasopressor support in septic shock patients, but experimental evidence suggests that selective V1A agonists are superior. The initial pharmacodynamic effects, pharmacokinetics, and safety of selepressin, a novel V1A-selective vasopressin analogue, was examined in a phase IIa trial in septic shock patients. METHODS: This was a randomized, double-blind, placebo-controlled multicenter trial in 53 patients in early septic shock (aged ≥18 years, fluid resuscitation, requiring vasopressor support) who received selepressin 1...
August 15, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28806532/the-impact-of-an-acute-oral-phosphate-load-on-endothelium-dependent-and-independent-brachial-artery-vasodilation-in-healthy-males
#9
Brendan M Levac, Michael A Adams, Kyra E Pyke
Serum phosphate levels are associated with cardiovascular morbidity and mortality in the general population and endothelial dysfunction may be mechanistically involved. The purpose of this study was to investigate the effects of acute phosphate supplementation on endothelial-dependent (Flow mediated dilation (FMD)) and -independent (Glyceryl trinitrate (GTN)) vasodilation in young, healthy males. 17 healthy male participants (23±3 years old) were exposed to an oral load of phosphate (PHOS; (liquid supplement containing 1200 mg of phosphorous) and placebo (PLAC) over two experimental days...
August 14, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28806211/the-opiorphin-analog-str-324-decreases-sensory-hypersensitivity-in-a-rat-model-of-neuropathic-pain
#10
Alain Van Elstraete, Philippe Sitbon, Leila Hamdi, Victor Juarez-Perez, Jean-Xavier Mazoit, Dan Benhamou, Catherine Rougeot
BACKGROUND: Neuropathic pain represents a therapeutic challenge, and treatments with increased efficacy and tolerability still need to be developed. Opiorphin protects endogenous enkephalins from degradation, potentiating enkephalin-dependent analgesia via the activation of opioid pathways. Enkephalins are natural ligands of opioid receptors, with strong affinity for δ-opioid receptors. Expression of functional δ-opioid receptors increases in sensory neurons after peripheral nerve injury in neuropathic pain models...
August 10, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28803772/perioperative-statins-do-not-prevent-acute-kidney-injury-after-cardiac-surgery-a-meta-analysis-of-randomized-controlled-trials
#11
Bing-Cheng Zhao, Pu Shen, Ke-Xuan Liu
OBJECTIVES: To evaluate whether perioperative statins reduce the risk of acute kidney injury (AKI) after cardiac surgery. DESIGN: Systematic review and meta-analysis of randomized trials. SETTING: Perioperative management in hospitals that perform cardiac surgery. PARTICIPANTS: Adult patients undergoing cardiac surgery. INTERVENTIONS: PubMed, EMBASE, and the Cochrane Library databases were searched for randomized trials...
April 21, 2017: Journal of Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/28803660/multiple-sclerosis-skin-induced-antigen-specific-immune-tolerance
#12
REVIEW
Paula Wildner, Krzysztof W Selmaj
Multiple sclerosis (MS) is a highly prevalent demyelinating disorder, presumed to be driven by an autoimmune response toward the central nervous system (CNS) components. All currently available treatments modulate the immune system globally and besides the reduction of disease activity, they may also impose considerable disturbances on the immune protective mechanisms. Thus, induction of antigen-specific immune tolerance remains the ultimate goal of MS therapy. Such approach carries promising therapeutic perspectives and, above all, a desirable safety profile...
August 2, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28801400/protein-misfolding-amyotrophic-lateral-sclerosis-and-guanabenz-protocol-for-a-phase-ii-rct-with-futility-design-promise-trial
#13
Eleonora Dalla Bella, Irene Tramacere, Giovanni Antonini, Giuseppe Borghero, Margherita Capasso, Claudia Caponnetto, Adriano Chiò, Massimo Corbo, Roberto Eleopra, Massimiliano Filosto, Fabio Giannini, Enrico Granieri, Vincenzo La Bella, Christian Lunetta, Jessica Mandrioli, Letizia Mazzini, Sonia Messina, Maria Rosaria Monsurrò, Gabriele Mora, Nilo Riva, Romana Rizzi, Gabriele Siciliano, Vincenzo Silani, Isabella Simone, Gianni Sorarù, Paolo Volanti, Giuseppe Lauria
INTRODUCTION: Recent studies suggest that endoplasmic reticulum stress may play a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) through an altered regulation of the proteostasis, the cellular pathway-balancing protein synthesis and degradation. A key mechanism is thought to be the dephosphorylation of eIF2α, a factor involved in the initiation of protein translation. Guanabenz is an alpha-2-adrenergic receptor agonist safely used in past to treat mild hypertension and is now an orphan drug...
August 11, 2017: BMJ Open
https://www.readbyqxmd.com/read/28801176/caffeine-use-in-the-neonatal-intensive-care-unit
#14
REVIEW
Jalal M Abu-Shaweesh, Richard J Martin
Caffeine is the most frequently used medication in the neonatal intensive care unit. It is used for the prevention and treatment of apnea, although this has been associated with lower incidence of bronchopulmonary dysplasia (BPD) and patent ductus arteriosus as well as intact survival at 18-21 months of life. Although neurodevelopmental advantage was no longer statistically significant at age 5 years, caffeine was associated with sustained improvement in co-ordination and less gross motor impairment than placebo...
August 8, 2017: Seminars in Fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28798505/an-enactive-account-of-placebo-effects
#15
Giulio Ongaro, Dave Ward
Placebos are commonly defined as ineffective treatments. They are treatments that lack a known mechanism linking their properties to the properties of the condition on which treatment aims to intervene. Given this, the fact that placebos can have substantial therapeutic effects looks puzzling. The puzzle, we argue, arises from the relationship placebos present between culturally meaningful entities (such as treatments or therapies), our intentional relationship to the environment (such as implicit or explicit beliefs about a treatment's healing powers) and bodily effects (placebo responses)...
2017: Biology & Philosophy
https://www.readbyqxmd.com/read/28796316/effects-of-tocilizumab-on-neutrophil-function-and-kinetics
#16
Laurence S C Lok, Neda Farahi, Jatinder K Juss, Chrystalla Loutsios, Chandra K Solanki, A Michael Peters, Francis Donaldson, Benjamin Porter-Brown, Edwin R Chilvers
BACKGROUND: Decreases in circulating neutrophils (polymorphonuclear leukocytes, PMNs) have been reported in patients treated with the anti-interleukin-6 receptor (IL-6R) antibody tocilizumab (TCZ); the mechanism for this is unclear. We hypothesize that TCZ reduces circulating neutrophils by affecting margination and / or bone marrow trafficking without affecting neutrophil function or apoptosis. MATERIALS AND METHODS: 18 healthy subjects were randomized to single intravenous dose of TCZ 8 mg/kg (n = 12) or placebo (n = 6) on day 0...
August 10, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28780512/repeated-administration-of-dapirolizumab-pegol-in-a-randomised-phase-i-study-is-well-tolerated-and-accompanied-by-improvements-in-several-composite-measures-of-systemic-lupus-erythematosus-disease-activity-and-changes-in-whole-blood-transcriptomic-profiles
#17
Chris Chamberlain, Peter J Colman, Ann M Ranger, Linda C Burkly, Geoffrey I Johnston, Christian Otoul, Christian Stach, Miren Zamacona, Thomas Dörner, Murray Urowitz, Falk Hiepe
OBJECTIVES: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease associated with diffuse immune cell dysfunction. CD40-CD40 ligand (CD40L) interaction activates B cells, antigen-presenting cells and platelets. CD40L blockade might provide an innovative treatment for systemic autoimmune disorders. We investigated the safety and clinical activity of dapirolizumab pegol, a polyethylene glycol conjugated anti-CD40L Fab' fragment, in patients with SLE. METHODS: This 32-week randomised, double-blind, multicentre study (NCT01764594) evaluated repeated intravenous administration of dapirolizumab pegol in patients with SLE who were positive for/had history of antidouble stranded DNA/antinuclear antibodies and were on stable doses of immunomodulatory therapies (if applicable)...
August 5, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28778047/metformin-treatment-significantly-enhances-intestinal-glucose-uptake-in-patients-with-type-2-diabetes-results-from-a-randomized-clinical-trial
#18
Jukka P Koffert, Kirsi Mikkola, Kirsi A Virtanen, Anna-Maria D Andersson, Linda Faxius, Kirsti Hällsten, Mikael Heglind, Letizia Guiducci, Tam Pham, Johanna M U Silvola, Jenni Virta, Olof Eriksson, Saila P Kauhanen, Antti Saraste, Sven Enerbäck, Patricia Iozzo, Riitta Parkkola, Maria F Gomez, Pirjo Nuutila
AIMS: Metformin therapy is associated with diffuse intestinal (18)F-fluoro-deoxyglucose (FDG) accumulation in clinical diagnostics using routine FDG-PET imaging. We aimed to study whether metformin induced glucose uptake in intestine is associated with the improved glycaemic control in patients with type 2 diabetes. Therefore, we compared the effects of metformin and rosiglitazone on intestinal glucose metabolism in patients with type 2 diabetes in a randomized placebo controlled clinical trial, and further, to understand the underlying mechanism, evaluated the effect of metformin in rats...
July 20, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28777756/long-term-effects-of-safinamide-on-mood-fluctuations-in-parkinson-s-disease
#19
Carlo Cattaneo, Thomas Müller, Erminio Bonizzoni, Gabriele Lazzeri, Ioannis Kottakis, Charlotte Keywood
BACKGROUND: Mood disorders are very frequent in Parkinson's Disease (PD), and their effective treatment is still a major unresolved issue: growing evidence suggests that glutamatergic system dysfunction is directly involved. Safinamide is a drug with an innovative mechanism of action, dopaminergic and non-dopaminergic, that includes the reversible inhibition of the monoamine oxidase-B (MAO-B) enzyme and the modulation of excessive glutamate release through the use- and state-dependent blockade of the sodium channels...
August 4, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28771393/single-dose-testosterone-administration-impairs-cognitive-reflection-in-men
#20
Gideon Nave, Amos Nadler, David Zava, Colin Camerer
In nonhumans, the sex steroid testosterone regulates reproductive behaviors such as fighting between males and mating. In humans, correlational studies have linked testosterone with aggression and disorders associated with poor impulse control, but the neuropsychological processes at work are poorly understood. Building on a dual-process framework, we propose a mechanism underlying testosterone's behavioral effects in humans: reduction in cognitive reflection. In the largest study of behavioral effects of testosterone administration to date, 243 men received either testosterone or placebo and took the Cognitive Reflection Test (CRT), which estimates the capacity to override incorrect intuitive judgments with deliberate correct responses...
August 1, 2017: Psychological Science
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