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https://www.readbyqxmd.com/read/28340340/selective-chemical-inhibition-of-pgc-1%C3%AE-gluconeogenic-activity-ameliorates-type-2-diabetes
#1
Kfir Sharabi, Hua Lin, Clint D J Tavares, John E Dominy, Joao Paulo Camporez, Rachel J Perry, Roger Schilling, Amy K Rines, Jaemin Lee, Marc Hickey, Melissa Bennion, Michelle Palmer, Partha P Nag, Joshua A Bittker, José Perez, Mark P Jedrychowski, Umut Ozcan, Steve P Gygi, Theodore M Kamenecka, Gerald I Shulman, Stuart L Schreiber, Patrick R Griffin, Pere Puigserver
Type 2 diabetes (T2D) is a worldwide epidemic with a medical need for additional targeted therapies. Suppression of hepatic glucose production (HGP) effectively ameliorates diabetes and can be exploited for its treatment. We hypothesized that targeting PGC-1α acetylation in the liver, a chemical modification known to inhibit hepatic gluconeogenesis, could be potentially used for treatment of T2D. Thus, we designed a high-throughput chemical screen platform to quantify PGC-1α acetylation in cells and identified small molecules that increase PGC-1α acetylation, suppress gluconeogenic gene expression, and reduce glucose production in hepatocytes...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28339380/a-simplified-extemporaneously-prepared-potassium-chloride-oral-solution
#2
Elias Tannous, Yana Tal, Kamal Amarny
Although commercial preparations of oral potassium supplements are usually available, there are times when our Medical Center is faced with situations in which the oral solution of potassium chloride is not available. This solution is necessary for our pediatric outpatients who cannot swallow tablets and need an oral solution. Moreover, there are no studies available which describe an extemporaneously prepared potassium chloride oral solution on which we can rely for assigning a beyond-use date. The aim of this study was to formulate an extemporaneous pediatric oral solution of potassium chloride and to determine the physical and chemical stability of this preparation...
September 2016: International Journal of Pharmaceutical Compounding
https://www.readbyqxmd.com/read/28333279/inhibition-of-pim1-kinase-attenuates-inflammation-induced-pro-labour-mediators-in-human-fetal-membranes-in-vitro
#3
Ratana Lim, Gillian Barker, Martha Lappas
STUDY QUESTION: Does proviral integration site for Moloney murine leukemic virus (PIM)1 kinase play a role in regulating the inflammatory processes of human labour and delivery? SUMMARY ANSWER: PIM1 kinase plays a critical role in fetal membranes in regulating pro-inflammatory and pro-labour mediators. WHAT IS KNOWN ALREADY: Infection and inflammation have strong causal links to preterm delivery by stimulating pro-inflammatory cytokines and collagen degrading enzymes, which can lead to rupture of membranes...
March 9, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28330856/-my-friend-who-bought-it-for-me-she-has-had-an-abortion-before-the-influence-of-ghanaian-women-s-social-networks-in-determining-the-pathway-to-induced-abortion
#4
Sarah D Rominski, Jody R Lori, Emmanuel Sk Morhe
BACKGROUND: Even given the liberal abortion law in Ghana, abortion complications are a large contributor to maternal morbidity and mortality. This study sought to understand why young women seeking an abortion in a legally enabling environment chose to do this outside the formal healthcare system. METHODS: Women being treated for complications arising from a self-induced abortion as well as for elective abortions at three hospitals in Ghana were interviewed. Community-based focus groups were held with women as well as men, separately...
March 22, 2017: Journal of Family Planning and Reproductive Health Care
https://www.readbyqxmd.com/read/28327380/monetary-costs-of-multiple-medication-use-for-the-treatment-of-individuals-in-recovery-from-chemical-dependency
#5
Corry D Bondi, Clinton P Kassi, Erica L Loadman, Khalid M Kamal, Vincent J Giannetti
No abstract text is available yet for this article.
March 9, 2017: Addictive Behaviors
https://www.readbyqxmd.com/read/28319221/fluorescent-chemical-probes-for-accurate-tumor-diagnosis-and-targeting-therapy
#6
REVIEW
Min Gao, Fabiao Yu, Changjun Lv, Jaebum Choo, Lingxin Chen
Surgical resection of solid tumors is currently the gold standard and preferred therapeutic strategy for cancer. Chemotherapy drugs also make a significant contribution by inhibiting the rapid growth of tumor cells and these two approaches are often combined to enhance treatment efficacy. However, surgery and chemotherapy inevitably lead to severe side effects and high systemic toxicity, which in turn results in poor prognosis. Precision medicine has promoted the development of treatment modalities that are developed to specifically target and kill tumor cells...
March 20, 2017: Chemical Society Reviews
https://www.readbyqxmd.com/read/28317922/optical-imaging-of-localized-chemical-events-using-programmable-diamond-quantum-nanosensors
#7
Torsten Rendler, Jitka Neburkova, Ondrej Zemek, Jan Kotek, Andrea Zappe, Zhiqin Chu, Petr Cigler, Jörg Wrachtrup
Development of multifunctional nanoscale sensors working under physiological conditions enables monitoring of intracellular processes that are important for various biological and medical applications. By attaching paramagnetic gadolinium complexes to nanodiamonds (NDs) with nitrogen-vacancy (NV) centres through surface engineering, we developed a hybrid nanoscale sensor that can be adjusted to directly monitor physiological species through a proposed sensing scheme based on NV spin relaxometry. We adopt a single-step method to measure spin relaxation rates enabling time-dependent measurements on changes in pH or redox potential at a submicrometre-length scale in a microfluidic channel that mimics cellular environments...
March 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28316788/chemical-pleurodesis-using-mistletoe-extracts-via-spray-catheter-during-medical-thoracoscopy-for-management-of-malignant-pleural-effusion
#8
Jung Seop Eom, Tae Hwa Kim, Geewon Lee, Hyo Yeong Ahn, Jeong Ha Mok, Min Ki Lee
We present three cases of successful chemical pleurodesis with a liquid solution of mistletoe extract using a spray catheter during medical thoracoscopy. The medical thoracoscopy was performed in all presented cases to remove pleural effusion and conduct chemical pleurodesis to manage symptomatic malignant pleural effusion. A spray catheter was used to instil the mistletoe extract evenly into the pleural cavity, and there were no pleurodesis-related complications. Respiratory symptoms caused by pleural effusion improved after pleurodesis, and successful pleurodesis was maintained for more than 3 months after medical thoracoscopy in all three patients...
May 2017: Respirology Case Reports
https://www.readbyqxmd.com/read/28315126/screening-for-main-components-associated-with-the-idiosyncratic-hepatotoxicity-of-a-tonic-herb-polygonum-multiflorum
#9
Chunyu Li, Ming Niu, Zhaofang Bai, Congen Zhang, Yanling Zhao, Ruiyu Li, Can Tu, Huifang Li, Jing Jing, Yakun Meng, Zhijie Ma, Wuwen Feng, Jinfa Tang, Yun Zhu, Jinjie Li, Xiaoya Shang, Zhengsheng Zou, Xiaohe Xiao, Jiabo Wang
The main constituents of a typical medicinal herb, Polygonum multiflorum (Heshouwu in Chinese), that induces idiosyncratic liver injury remain unclear. Our previous work has shown that cotreatment with a nontoxic dose of lipopolysaccharide (LPS) and therapeutic dose of Heshouwu can induce liver injury in rats, whereas the solo treatment cannot induce observable injury. In the present work, using the constituent "knock-out" and "knock-in" strategy, we found that the ethyl acetate (EA) extract of Heshouwu displayed comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats...
March 17, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28315072/direct-myosin-activation-by-omecamtiv-mecarbil-for-heart-failure-with-reduced-ejection-fraction
#10
Mitchell A Psotka, John R Teerlink
Myosin is the indispensable molecular motor that utilizes chemical energy to produce force for contraction within the cardiac myocyte. Myosin activity is gated by intracellular calcium levels which are regulated by multiple upstream signaling cascades that can be altered for clinical utility using inotropic medications. In contrast to clinically available cardiac inotropes, omecamtiv mecarbil is a novel direct myosin activator developed to augment left ventricular systolic function without the undesirable secondary effects of altered calcium homeostasis...
March 18, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28314746/protocol-for-a-cluster-randomised-stepped-wedge-trial-assessing-the-impact-of-a-community-level-hygiene-intervention-and-a-water-intervention-using-riverbank-filtration-technology-on-diarrhoeal-prevalence-in-india
#11
Sarah L McGuinness, Joanne E O'Toole, Thomas B Boving, Andrew B Forbes, Martha Sinclair, Sumit K Gautam, Karin Leder
INTRODUCTION: Diarrhoea is a leading cause of death globally, mostly occurring as a result of insufficient or unsafe water supplies, inadequate sanitation and poor hygiene. Our study aims to investigate the impact of a community-level hygiene education program and a water quality intervention using riverbank filtration (RBF) technology on diarrhoeal prevalence. METHODS AND ANALYSIS: We have designed a stepped wedge cluster randomised trial to estimate the health impacts of our intervention in 4 rural villages in Karnataka, India...
March 17, 2017: BMJ Open
https://www.readbyqxmd.com/read/28314413/recent-progress-in-the-discovery-and-development-of-trpa1-modulators
#12
S Skerratt
TRPA1 is a well-validated therapeutic target in areas of high unmet medical need that include pain and respiratory disorders. The human genetic rationale for TRPA1 as a pain target is provided by a study describing a rare gain-of-function mutation in TRPA1, causing familial episodic pain syndrome. There is a growing interest in the TRPA1 field, with many pharmaceutical companies reporting the discovery of TRPA1 chemical matter; however, GRC 17536 remains to date the only TRPA1 antagonist to have completed Phase IIa studies...
2017: Progress in Medicinal Chemistry
https://www.readbyqxmd.com/read/28306345/a-retrospective-study-on-non-drug-related-poisoning-in-the-community-among-children-from-south-india
#13
Debasis Das Adhikari, Saibal Das, Blessed Winston A, Kaysina Vazhudhi, Aniket Kumar, Margaret Shanthi Fx, Indira Agarwal
OBJECTIVES: This retrospective study was performed to determine the incidence, demographic distribution, types and outcomes across various non-drug related poisonings among children attending a tertiary care center in south India. METHODS: All children from 0-16 years who presented to the Paediatric Emergency Department, Christian Medical College, Vellore with non-drug related poisoning from October 2004 to September 2013 were included. RESULTS: Out of the total 997 cases of poisoning, 629 (63...
March 17, 2017: Hospital Practice (Minneapolis)
https://www.readbyqxmd.com/read/28303498/validation-of-a-preclinical-drug-screening-platform-for-pharmacoresistant-epilepsy
#14
Melissa L Barker-Haliski, Kristina Johnson, Peggy Billingsley, Jennifer Huff, Laura J Handy, Rizvana Khaleel, Zhenmei Lu, Matthew J Mau, Timothy H Pruess, Carlos Rueda, Gerald Saunders, Tristan K Underwood, Fabiola Vanegas, Misty D Smith, Peter J West, Karen S Wilcox
The successful identification of promising investigational therapies for the treatment of epilepsy can be credited to the use of numerous animal models of seizure and epilepsy for over 80 years. In this time, the maximal electroshock test in mice and rats, the subcutaneous pentylenetetrazol test in mice and rats, and more recently the 6 Hz assay in mice, have been utilized as primary models of electrically or chemically-evoked seizures in neurologically intact rodents. In addition, rodent kindling models, in which chronic network hyperexcitability has developed, have been used to identify new agents...
March 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28303218/the-modification-of-natural-products-for-medical-use
#15
REVIEW
Zongru Guo
Drug innovation is characterized by painstaking molecular-level syntheses and modifications as the basic components of research and development. Similarly, natural products are chemically tailored and modified based upon their structural and biological properties. To some extent, the modification of natural products is quite different from de novo structure-based drug discovery. This review describes the general strategies and principles for the modification of natural products to drugs, as illustrated by several successful medicines that originated from natural products...
March 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28302088/a-systematic-review-including-meta-analysis-of-work-environment-and-burnout-symptoms
#16
Gunnar Aronsson, Töres Theorell, Tom Grape, Anne Hammarström, Christer Hogstedt, Ina Marteinsdottir, Ingmar Skoog, Lil Träskman-Bendz, Charlotte Hall
BACKGROUND: Practitioners and decision makers in the medical and insurance systems need knowledge on the relationship between work exposures and burnout. Many burnout studies - original as well as reviews - restricted their analyses to emotional exhaustion or did not report results on cynicism, personal accomplishment or global burnout. To meet this need we carried out this review and meta-analyses with the aim to provide systematically graded evidence for associations between working conditions and near-future development of burnout symptoms...
March 16, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28295128/medically-unexplained-physical-symptoms-mups-among-adults-in-canada-comorbidity-health-care-use-and-employment
#17
Jungwee Park, Heather Gilmour
Based on data from the 2014 Canadian Community Health Survey and the 2012 Canadian Community Health Survey-Mental Health, this study provides estimates of the prevalence of medically unexplained physical symptoms (MUPS) in the household population aged 25 or older. MUPS are examined in relation to sociodemographic characteristics, physical and mental comorbidity, health care use and unmet needs, labour force participation and productivity. In 2014, 5.5% of Canadian adults-an estimated 1.3 million - reported having chronic fatigue syndrome (1...
March 15, 2017: Health Reports
https://www.readbyqxmd.com/read/28293633/combined-ligand-structure-based-virtual-screening-and-molecular-dynamics-simulations-of-steroidal-androgen-receptor-antagonists
#18
Yuwei Wang, Rui Han, Huimin Zhang, Hongli Liu, Jiazhong Li, Huanxiang Liu, Paola Gramatica
The antiandrogens, such as bicalutamide, targeting the androgen receptor (AR), are the main endocrine therapies for prostate cancer (PCa). But as drug resistance to antiandrogens emerges in advanced PCa, there presents a high medical need for exploitation of novel AR antagonists. In this work, the relationships between the molecular structures and antiandrogenic activities of a series of 7α-substituted dihydrotestosterone derivatives were investigated. The proposed MLR model obtained high predictive ability...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28291347/production-of-odd-carbon-dicarboxylic-acids-in-escherichia-coli-using-an-engineered-biotin-fatty-acid-biosynthetic-pathway
#19
Robert W Haushalter, Ryan M Phelan, Kristina M Hoh, Cindy Su, George Wang, Edward E K Baidoo, Jay D Keasling
Dicarboxylic acids are commodity chemicals used in the production of plastics, polyesters, nylons, fragrances, and medications. Bio-based routes to dicarboxylic acids are gaining attention due to environmental concerns about petroleum-based production of these compounds. Some industrial applications require dicarboxylic acids with specific carbon chain lengths, including odd-carbon species. Biosynthetic pathways involving cytochrome P450-catalyzed oxidation of fatty acids in yeast and bacteria have been reported, but these systems produce almost exclusively even-carbon species...
March 21, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28291335/effect-of-chemical-and-physical-properties-on-the-in-vitro-degradation-of-3d-printed-high-resolution-poly-propylene-fumarate-scaffolds
#20
Jason M Walker, Emily Bodamer, Olivia Krebs, YuanYuan Luo, Alex P Kleinfehn, Matthew L Becker, David Dean
Two distinct molecular masses of poly(propylene fumarate) (PPF) are combined with an additive manufacturing process to fabricate highly complex scaffolds possessing controlled chemical properties and porous architecture. Scaffolds were manufactured with two polymer molecular masses and two architecture styles. Degradation was assessed in an accelerated in vitro environment. The purpose of the degradation study is not to model or mimic in vivo degradation, but to efficiently compare the effect of modulating scaffold properties...
March 14, 2017: Biomacromolecules
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