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Elena S Don, Alexandra G Emelyanova, Natalia N Yakovleva, Nataliia V Petrova, Marina V Nikiforova, Evgeniy A Gorbunov, Sergey A Tarasov, Sergey G Morozov, Oleg I Epstein
The assessment of dose-response is an essential part of drug development in terms of the determination of a drug's effective dose, finding the safety endpoint, estimation of the pharmacokinetic profile and even validation of drug activity, especially for therapeutic agents with a principally novel mechanism of action. Drugs based on released-active forms of antibodies are a good example of such a target. In this study, the efficacy of the antiviral drug Anaferon for children (released-active form of antibodies to interferon-gamma) was tested in a dose-dependent manner (at doses of 0...
October 21, 2016: Journal of Medical Virology
Rania R Abdelaziz, Wagdi F Elkashef, Eman Said
Silicosis is a crippling respiratory disorder characterized by massive lung inflammation and fibrosis. The current study provides evidence on the protective potential of tadalafil; a specific phosphodiesterase-5 (PDE-5) inhibitor against experimentally-induced pulmonary silicosis in rats. Silicosis was induced by intranasal instillation of crystalline silica (50mg/rat). Halofuginone hydrobromide; a standard collagen-1 synthesis inhibitor was selected as a reference anti-fibrotic. Daily oral administration of tadalafil (1mg/kg) for 8weeks significantly ameliorated silica-induced pulmonary damage...
October 18, 2016: International Immunopharmacology
Jing Qiu, Min Wang, Jun Zhang, Qing Cai, Dan Lu, Yansong Li, Yushu Dong, Tianzhi Zhao, Huisheng Chen
Neuroinflammation remains the primary cause of morbidity and mortality in stroke-induced secondary brain injury. The NOD-like receptor pyrin 3 (NLRP3) inflammasome is involved in diverse inflammatory diseases, including cerebral ischemia, and is thus considered an effective therapeutic target. In the present study, we investigated the neuroprotection of Sinomenine (SINO), a potent natural anti-apoptotic and anti-inflammatory molecule, against cerebral ischemia in a mouse model of middle cerebral artery occlusion (MCAO) in vivo and in an oxygen glucose deprivation (OGD)-treated astrocytes/microglia model in vitro...
October 18, 2016: International Immunopharmacology
Young-Min Kim, Thrimoorthy Potta, Keun-Hong Park, Soo-Chang Song
An injectable hydrogel showing temperature-dependent chemical crosslinking was developed to combine injectabilities of physical hydrogels with dense structures of chemical hydrogels for applications in stem cell delivery-mediated tissue regeneration systems showing easy administration and maintenance of well-dispersed cells within the hydrogel. Hydrophobic methacryl groups were applied to thermosensitive poly(organophosphazenes) to induce temperature mediated hydrophobic interaction and chemical crosslinking...
October 13, 2016: Biomaterials
Yi Wang, Yao-Xin Lin, Sheng-Lin Qiao, Hong-Wei An, Yang Ma, Zeng-Ying Qiao, R P Yeshan J Rajapaksha, Hao Wang
Immunotherapy has shown a promising effect for a variety of cancers. However, the immune treatment efficiency of solid tumor is limited due to barely infiltration of immune cells in solid tumor. Researchers realized conversion of tumor supportive macrophages to tumor against ones was an effective method to induce the functional reverse of macrophage and contributed to the subsequent antitumor response. The current challenge in the field is that while making use of cytokines usually coupled with poor-distribution and systemic side effects...
October 4, 2016: Biomaterials
Ning Jia, Qinru Sun, Qian Su, Shaokang Dang, Guomin Chen
Substantial evidence has shown that the oxidative damage to hippocampal neurons is associated with the cognitive impairment induced by adverse stimuli during gestation named prenatal stress (PS). Taurine, a conditionally essential amino acid, possesses multiple roles in the brain as a neuromodulator or antioxidant. In this study, to explore the roles of taurine in PS-induced learning and memory impairment, prenatal restraint stress was set up and Morris water maze (MWM) was employed for testing the cognitive function in the one-month-old rat offspring...
October 13, 2016: Redox Biology
Marco A Ferraz Nogueira Filho, Cody J Peer, Jeffers Nguyen, Amy McCalla, Lee Helman, William D Figg
The Aurora kinase family facilitates cell division through various processes and is overexpressed in a wide variety of human cancers, leading to aneuploidy. For that reason, these enzymes are currently targets of a rising class of anticancer drugs, with some molecules already in therapeutic use. In this study, a new UHPLC-MS/MS method was developed and validated to quantitate a new pan Aurora kinase inhibitor still in preclinical development, SCH-1473759. This bioanalytical method employed a liquid-liquid extraction from plasma using ethyl acetate before evaporation...
October 5, 2016: Journal of Pharmaceutical and Biomedical Analysis
Laura de Diego-García, Mercedes Ramírez-Escudero, Álvaro Sebastián-Serrano, Juan Ignacio Diaz-Hernández, Jesús Pintor Just, José J Lucas, Miguel Díaz-Hernández
The Ubiquitin-Proteasome System (UPS) is essential for the regulation of the cellular proteostasis. Indeed, it has been postulated that an UPS dysregulation is the common mechanism that underlies several neurological disorders. Considering that extracellular nucleotides, through their selective P2Y2 receptor (P2Y2R), play a neuroprotective role in various neurological disorders that course with an UPS impairment, we wonder if this neuroprotective capacity resulted from their ability to modulate the UPS. Using a cellular model expressing two different UPS reporters, we found that the stimulation of P2Y2R by its selective agonist Up4U induced a significant reduction of UPS reporter levels...
October 18, 2016: Biochimica et Biophysica Acta
Tomohiro Yamashita, Shota Yamamoto, Jiaming Zhang, Miho Kometani, Daisuke Tomiyama, Keita Kohno, Hidetoshi Tozaki-Saitoh, Kazuhide Inoue, Makoto Tsuda
P2X4 receptors (P2X4R) are a family of ATP-gated non-selective cation channels. We previously demonstrated that activation of P2X4R in spinal microglia is crucial for neuropathic pain, a highly debilitating chronic pain condition, suggesting that P2X4R is a potential therapeutic target for treating neuropathic pain. Thus, the identification of a compound that has a potent inhibitory effect on P2X4R is an important clinical challenge. In the present study, we screened a chemical library of clinically approved drugs and show for the first time that duloxetine, a serotonin and noradrenaline reuptake inhibitor, has an inhibitory effect on rodent and human P2X4R...
2016: PloS One
Wang Wei, Zhang Wei-Sheng, Alayi Ahan, Yan Ci, Zhang Wei-Wen, Cao Ming-Qin
OBJECTIVE: This study was aimed to find out epidemiologic characteristic of tuberculosis (TB) cases, and Human Immunodeficiency Virus (HIV) positive cases among TB patients (TB/HIV co-infection) through demographic, temporal, and spatial study in Urumqi. METHODS: Descriptive statistics and multivariate logistic regression were applied to identify the epidemiologic characteristics and risk factors of TB epidemic and TB/HIV co-infection epidemic. All addresses of each TB case, TB/HIV co-infection case, and administrative street were transformed into geographical coordinate...
2016: PloS One
Aaron S Kesselheim, Wesley Eddings, Tara Raj, Eric G Campbell, Jessica M Franklin, Kathryn M Ross, Lisa A Fulchino, Jerry Avorn, Joshua J Gagne
BACKGROUND: Generic drugs are cost-effective versions of brand-name drugs approved by the Food and Drug Administration (FDA) following proof of pharmaceutical equivalence and bioequivalence. Generic drugs are widely prescribed by physicians, although there is disagreement over the clinical comparability of generic drugs to brand-name drugs within the physician community. The objective of this survey was to assess physicians' perceptions of generic drugs and the generic drug approval process...
2016: PloS One
Tonya L K Miller, Raymond Park, Lena S Sun
On April 16 and 17, 2016, the Pediatric Anesthesia and Neurodevelopment Assessment (PANDA) study held its fifth biennial symposium at the Morgan Stanley Children's Hospital of New York. The PANDA symposium has served as a key forum for clinicians, researchers, and other major stakeholders to gather and review the current state of preclinical and clinical research related to anesthetic neurotoxicity in children. Goals of the meeting included assessing how current knowledge has translated and impacted clinical care of patients who may be at risk, and future directions for research and policy...
October 2016: Journal of Neurosurgical Anesthesiology
Caterina Magnani, Diana Giannarelli, Giuseppe Casale
OBJECTIVES: To assess the prevalence of breakthrough pain (BTP) provoked by 6 common procedures in patients with advanced disease. METHODS: A prospective, cross-sectional, multicenter, national study was performed in 23 palliative care units in Italy. Patients were recruited if they were undergoing one of the following procedures as part of normal care: turning, personal hygiene care, transfer from bed to chair, bladder catheterization, pressure ulcer care, and subcutaneous drug administration...
October 20, 2016: Clinical Journal of Pain
J Ellison, C Nagamuthu, S Vanderloo, B McRae, C Waters
INTRODUCTION: Chronic disease rates are produced from the Public Health Agency of Canada's Canadian Chronic Disease Surveillance System (CCDSS) using administrative health data from provincial/territorial health ministries. Denominators for these rates are based on estimates of populations derived from health insurance files. However, these data may not be accessible to all researchers. Another source for population size estimates is the Statistics Canada census. The purpose of our study was to calculate the major differences between the CCDSS and Statistics Canada's population denominators and to identify the sources or reasons for the potential differences between these data sources...
October 2016: Health Promotion and Chronic Disease Prevention in Canada
Marybeth Grant-Beuttler, Jenifer Jennings, Christina McCauley, Robert Dulay, Katlyn Grossnickle, Kerri Kill, John Hay
PURPOSE: To develop an electronic version of the Children's Self-Perceptions of Adequacy in and Predilection for Physical Activity (eCSAPPA), which would allow individual administration to children younger than nine years of age. METHODS: Fifty-four, four - nine-year-old children completed the eCSAPPA and the Test of Gross Motor Development-2 (TGMD-2). Parental measures of physical activity, and body mass index were obtained. Twenty-one participants additionally completed the paper version of the CSAPPA...
October 21, 2016: Pediatric Exercise Science
Matthijs T W Veltmeijer, Dineke Veeneman, Coen C C W Bongers, Mihai G Netea, Jos W van der Meer, Thijs M H Eijsvogels, Maria T E Hopman
PURPOSE: Exercise increases core body temperature (TC) due to metabolic heat production. However, the exercise-induced release of inflammatory cytokines including interleukin-6 may also contribute to the rise in TC by increasing the hypothalamic temperature setpoint. We aimed to investigate whether the exercise-induced increase in TC is partly caused by an altered hypothalamic temperature setpoint. METHODS: 15 healthy, active male subjects aged 36±14 years were recruited...
September 26, 2016: International Journal of Sports Physiology and Performance
(no author information available yet)
This document provides the final text of regulations governing employee protection (retaliation or whistleblower) claims under section 1558 of the Affordable Care Act, which added section 18C to the Fair Labor Standards Act to provide protections to employees who may have been subject to retaliation for seeking assistance under certain affordability assistance provisions (for example, health insurance premium tax credits) or for reporting potential violations of the Affordable Care Act's consumer protections (for example, the prohibition on rescissions)...
October 13, 2016: Federal Register
Olga Tursunov, Nathan I Cherny, Freda DeKeyser Ganz
PURPOSE/OBJECTIVES: To describe the experience of family members of patients receiving palliative sedation at the initiation of treatment and after the patient has died and to compare these experiences over time.
. DESIGN: Descriptive comparative study.
. SETTING: Oncology ward at Shaare Zedek Medical Center in Jerusalem, Israel.
. SAMPLE: A convenience sample of 34 family members of dying patients receiving palliative sedation...
November 1, 2016: Oncology Nursing Forum
Alexander N Zelikin, Carsten Ehrhardt, Anne Marie Healy
Biological drugs generated via recombinant techniques are uniquely positioned due to their high potency and high selectivity of action. The major drawback of this class of therapeutics, however, is their poor stability upon oral administration and during subsequent circulation. As a result, biological drugs have very low bioavailability and short therapeutic half-lives. Fortunately, tools of chemistry and biotechnology have been developed into an elaborate arsenal, which can be applied to improve the pharmacokinetics of biological drugs...
October 21, 2016: Nature Chemistry
Dennis Chan, Laura Marie Gallaher, Kuven Moodley, Ludovico Minati, Neil Burgess, Tom Hartley
This protocol describes the administration of the 4 Mountains Test (4MT), a short test of spatial memory, in which memory for the topographical layout of four mountains within a computer-generated landscape is tested using a delayed match-to-sample paradigm. Allocentric spatial memory is assessed by altering the viewpoint, colors and textures between the initially presented and target images. Allocentric spatial memory is a key function of the hippocampus, one of the earliest brain regions to be affected in Alzheimer's disease (AD) and impairment of hippocampal function predates the onset of dementia...
October 13, 2016: Journal of Visualized Experiments: JoVE
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