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Drug diversion

Peter D Koch, Howard R Miller, Gary Yu, John A Tallarico, Peter K Sorger, Yuan Wang, Yan Feng, Jason R Thomas, Nathan T Ross, Timothy Mitchison
We screened a library of bioactive small molecules for activators and inhibitors of innate immune signaling through IRF3 and NFkB pathways with the goals of advancing pathway understanding and discovering probes for immunology research. We used high content screening to measure the translocation from the cytoplasm to nucleus of IRF3 and NFkB in primary human macrophages; these transcription factors play a critical role in the activation of STING and other pro-inflammatory pathways. Our pathway activator screen yielded a diverse set of hits that promoted nuclear translocation of IRF3 and/or NFkB, but the majority of these compounds did not cause activation of downstream pathways...
March 19, 2018: ACS Chemical Biology
Ya-Qi Wang, Jiao-Jiao Jiao, Zhen-Feng Wu, Qin Zheng, Ming Yang
"High quality, safety and effectiveness" are the primary principles for the pharmaceutical research and development process in China. The quality of products relies not only on the inspection method, but also on the design and development, process control and standardized management. The quality depends on the process control level. In this paper, the history and current development of quality control of traditional Chinese medicine (TCM) preparations are reviewed systematically. Based on the development model of international drug quality control and the misunderstanding of quality control of TCM preparations, the reasons for impacting the homogeneity of TCM preparations are analyzed and summarized...
January 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Sameh S M Soliman, Manish N Raizada
Fungal Taxol acquired lots of attention in the last few decades mainly because of the hope that fungi could be manipulated more easily than yew trees to scale up the production level of this valuable anticancer drug. Several researchers have studied diverse factors to enhance fungal Taxol production. However, up to date fungal Taxol production has never been enhanced to the commercial level. We have hypothesized that optimization of fungal Taxol production may require clear understanding of the fungal habitat in its original host plant...
2018: Frontiers in Microbiology
Stuart Maudsley, Viswanath Devanarayan, Bronwen Martin, Hugo Geerts
Biomedical data sets are becoming increasingly larger and a plethora of high-dimensionality data sets ("Big Data") are now freely accessible for neurodegenerative diseases, such as Alzheimer's disease. It is thus important that new informatic analysis platforms are developed that allow the organization and interrogation of Big Data resources into a rational and actionable mechanism for advanced therapeutic development. This will entail the generation of systems and tools that allow the cross-platform correlation between data sets of distinct types, for example, transcriptomic, proteomic, and metabolomic...
March 15, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Brian J Piper, Dipam T Shah, Olapeju M Simoyan, Kenneth L McCall, Stephanie D Nichols
INTRODUCTION: The U.S. is experiencing an opioid epidemic which is at least partially iatrogenic and fueled by both prescription and illicit misuse. This study provides a nationwide examination of opioid distribution patterns during the last decade. METHODS: Data were obtained from the U.S. Drug Enforcement Administration's Automation of Reports and Consolidated Orders System for 2006-2016. Analyses include quantities of ten opioids legally dispensed nationwide by weight and converted to Morphine Milligram Equivalents...
March 9, 2018: American Journal of Preventive Medicine
Anna Rubio-Cosials, Eike C Schulz, Lotte Lambertsen, Georgy Smyshlyaev, Carlos Rojas-Cordova, Kristoffer Forslund, Ezgi Karaca, Aleksandra Bebel, Peer Bork, Orsolya Barabas
Conjugative transposition drives the emergence of multidrug resistance in diverse bacterial pathogens, yet the mechanisms are poorly characterized. The Tn1549 conjugative transposon propagates resistance to the antibiotic vancomycin used for severe drug-resistant infections. Here, we present four high-resolution structures of the conserved Y-transposase of Tn1549 complexed with circular transposon DNA intermediates. The structures reveal individual transposition steps and explain how specific DNA distortion and cleavage mechanisms enable DNA strand exchange with an absolute minimum homology requirement...
March 2, 2018: Cell
Stephanie Makhoul, Elena Walter, Oliver Pagel, Ulrich Walter, Albert Sickmann, Stepan Gambaryan, Albert Smolenski, René P Zahedi, Kerstin Jurk
Platelets are circulating sentinels of vascular integrity and are activated, inhibited, or modulated by multiple hormones, vasoactive substances or drugs. Endothelium- or drug-derived NO strongly inhibits platelet activation via activation of the soluble guanylate cyclase (sGC) and cGMP elevation, often in synergy with cAMP-elevation by prostacyclin. However, the molecular mechanisms and diversity of cGMP effects in platelets are poorly understood and sometimes controversial. Recently, we established the quantitative human platelet proteome, the iloprost/prostacyclin/cAMP/protein kinase A (PKA)-regulated phosphoproteome, and the interactions of the ADP- and iloprost/prostacyclin-affected phosphoproteome...
March 14, 2018: Nitric Oxide: Biology and Chemistry
Deepti Singh, Shwetha Narayanamoorthy, Sunita Gamre, Ananda Guha Majumdar, Manish Goswami, Umesh Gami, Susan Cherian, Mahesh Subramanian
Antibiotic resistance is a global problem and there is an urgent need to augment the arsenal against pathogenic bacteria. The emergence of different drug resistant bacteria is threatening human lives to be pushed towards the pre-antibiotic era. Botanical sources remain a vital source of diverse organic molecules that possess antibacterial property as well as augment existing antibacterial molecules. Piper betle, a climber, is widely used in south and south-east Asia whose leaves and nuts are consumed regularly...
March 14, 2018: Free Radical Biology & Medicine
Jenna L McCauley, Renata S Leite, Valeria V Gordan, Roger B Fillingim, Gregg H Gilbert, Cyril Meyerowitz, David Cochran, D Brad Rindal, Kathleen T Brady
BACKGROUND: Minimal information exists regarding the consistency and correlates of dentists' implementation of risk mitigation strategies when prescribing opioids, including risk screening, prescription drug monitoring program (PDMP) use, and patient education. METHODS: The authors conducted a Web-based, cross-sectional survey among practicing dentist members of The National Dental Practice-Based Research Network. The authors used the survey to assess pain management prescribing practices and risk mitigation implementation...
March 14, 2018: Journal of the American Dental Association
Ahmed Ma'mun, Mohamed K Abd El-Rahman, Mohamed Abd El-Kawy
In recent years, the whole field of ion-selective electrodes(ISEs) in pharmaceutical sciences has expanded far beyond its original roots. The diverse range of opportunities offered by ISEs was broadly used in a number of pharmaceutical applications, with topics presented ranging from bioanalysis of drugs and metabolites, to protein binding studies, green analytical chemistry, impurity profiling, and drug dissolution in biorelevant media. Inspired from these advances and with the aim of extending the functional capabilities of ISEs, the primary focus of the present paper is the utilization of ISE as a tool in personalized medicine...
February 7, 2018: Journal of Pharmaceutical and Biomedical Analysis
Zihao Wang, Yifan Ma, YanXiang Wang, Yutong Liu, Kai Chen, Zihan Wu, Shuang Yu, Yuan Yuan, Changsheng Liu
Poly (glycerol sebacate) (PGS), a tough elastomer, has been widely explored in tissue engineering due to the desirable mechanical properties and biocompatibility. However, the complex curing procedure (high temperature and vacuum) and limited hydrophilicity (∼90° of wetting angle) greatly impede its functionalities. To address these challenges, a urethane-based low-temperature setting, PEGylated PGS bioelastomer was developed with and without solvent. By simultaneously tailoring PEG and hexamethylene diisocyanate (HDI) contents, the elastomers X-P-mUs (X referred to the PEG content and m referred to HDI content) with a broad ranging mechanical properties and customized hydrophilicity were constructed...
March 13, 2018: Acta Biomaterialia
Shaoxin Feng, Nathaniel D Catron, Alan Donghua Zhu, John M Lipari, Jianwei Wu, Yi Gao, Geoff G Z Zhang
Micellar solubilization is an important concept in the delivery of poorly water-soluble drugs. The rational selection of the type and the amount of surfactant to be incorporated in a formulation require comprehensive solubility studies. These studies are time and material demanding, both of which are scarce, especially during late discovery and early development stages. We hypothesized that, if the solubilization mechanism or molecular interaction is similar, the solubilization capacity ratio (SCR, a newly defined parameter) is dictated by micellar structures, independent of drugs...
March 13, 2018: Journal of Pharmaceutical Sciences
Noam Zilberman, Gal Yadid, Yaniv Efrati, Yehuda Neumark, Yuri Rassovsky
Substance-related and behavioral addictions are extremely prevalent and represent a major public health concern. In the ongoing attempt to understand the addictive personality, contradictory results have arisen from studies that have explored personality traits in different addiction populations. The diversity across addiction types suggests that some of these inconsistencies stem from distinct personalities underlying each addiction. The present study compares the personality profiles of several addictions, representing both substance (drugs and alcohol) and behavioral (gambling and sex) subtypes...
March 6, 2018: Addictive Behaviors
Andrew McDowell, Neeraj Raizada, Sunil D Khaparde, Raghuram Rao, Sanjay Sarin, Aakshi Kalra, Virender Singh Salhotra, Sreenivas Achuthan Nair, Catharina Boehme, Claudia M Denkinger
BACKGROUND: Diagnosing tuberculosis (TB) in children presents considerable challenges. Upfront testing on Xpert® MTB/RIF ('Xpert')-a rapid molecular assay with high sensitivity and specificity-for pediatric presumptive TB patients, as recommended by India's Revised National Tuberculosis Control Program (RNTCP), can pave the way for early TB diagnosis. As part of an ongoing project implemented by Foundation for Innovative New Diagnostics (FIND) dedicated to providing upfront free-of-cost (FOC) Xpert testing to children seeking care in the public and private sectors, a qualitative assessment was designed to understand how national guidelines on TB diagnosis and Xpert technology have been integrated into the pediatric TB care practices of different health providers...
2018: PloS One
Caterina Musolino, Giacomo Oteri, Alessandro Allegra, Manuela Mania, Angela D'Ascola, Angela Avenoso, Vanessa Innao, Andrea Gaetano Allegra, Salvatore Campo
Bisphosphonates are formidable inhibitors of osteoclast-mediated bone resorption employed for therapy of multiple myeloma (MM) subjects with osteolytic lesions. Osteonecrosis of the jaw (ONJ) is an uncommon drug-induced adverse event of these agents. MicroRNAs (miRNAs) are a group of small, noncoding RNAs nucleotides, which are essential post-transcriptional controllers of gene expression. They have a central role in the normal bone development. The goal of our study was to investigate 18 miRNAs, whose targets were previously validated and described in MM subjects without ONJ, in peripheral lymphocytes of MM subjects with bisphosphonate-induced ONJ...
March 15, 2018: Annals of Hematology
Matthew V Helliwell, Yihong Zhang, Aziza El Harchi, Chunyun Du, Jules C Hancox, Christopher E Dempsey
Cardiac potassium channels encoded by human Ether-à-go-go Related Gene (hERG) are major targets for structurally diverse drugs associated with acquired long QT syndrome. This study characterized hERG channel inhibition by a minimally structured high affinity hERG inhibitor, Cavalli-2, composed of three phenyl groups linked by polymethylene spacers around a central amino group, chosen to probe the spatial arrangement of side chain groups in the high-affinity drug binding site of the hERG pore. hERG current (IhERG ) recorded at physiological temperature from HEK 293 cells was inhibited with an IC50 of 35...
March 15, 2018: Journal of Biological Chemistry
Daniel E O'Brien, Douglas M Shaw, Hyekyung P Cho, Alan J Cross, Steven S Wesolowski, Andrew S Felts, Jonas Bergare, Charles S Elmore, Craig W Lindsley, Colleen M Niswender, P Jeffrey Conn
Allosteric modulation of metabotropic glutamate receptor 2 (mGlu2) has demonstrated efficacy in preclinical rodent models of several brain disorders, leading to industry and academic drug discovery efforts. Although the pharmacology and binding sites of some mGlu2 allosteric modulators have been characterized previously, questions remain about the nature of the allosteric mechanism of cooperativity with glutamate and whether structurally diverse allosteric modulators bind in an identical manner to specific allosteric sites...
March 15, 2018: Molecular Pharmacology
Christopher J Lambert, Briana C Freshner, Arlen Chung, Tamara J Stevenson, D Miranda Bowles, Raheel Samuel, Bruce K Gale, Joshua L Bonkowsky
Zebrafish are a valuable model organism in biomedical research. Their rapid development, ability to model human diseases, utility for testing genetic variants identified from next-generation sequencing, amenity to CRISPR mutagenesis, and potential for therapeutic compound screening, has led to their wide-spread adoption in diverse fields of study. However, their power for large-scale screens is limited by the absence of automated genotyping tools for live animals. This constrains potential drug screen options, limits analysis of embryonic and larval phenotypes, and requires raising additional animals to adulthood to ensure obtaining an animal of the desired genotype...
2018: PloS One
Daniela Munro-Rojas, Esdras Fernandez-Morales, José Zarrabal-Meza, Ma Teresa Martínez-Cazares, Aurora Parissi-Crivelli, Javier Fuentes-Domínguez, Marie Nancy Séraphin, Michael Lauzardo, Jorge Alberto González-Y-Merchand, Sandra Rivera-Gutierrez, Roberto Zenteno-Cuevas
BACKGROUND: Mexico is one of the most important contributors of drug and multidrug-resistant tuberculosis in Latin America; however, knowledge of the genetic diversity of drug-resistant tuberculosis isolates is limited. METHODS: In this study, the genetic structure of 112 Mycobacterium tuberculosis strains from the southeastern Mexico was determined by spoligotyping and 24-loci MIRU-VNTRs. FINDINGS: The results show eight major lineages, the most of which was T1 (24%), followed by LAM (16%) and H (15%)...
2018: PloS One
Mehmet F Aydın, Emre Adıgüzel, Hakan Güzel
To determine the knowledge, attitudes, practices, and awareness for risk factors associated with cystic echinococcosis (CE) among animal breeders, nurses, nursing students, dietitians, food professionals and other public groups in Turkey. Methods: Questionnaire forms were prepared in compliance with the individuals' diversity, and a survey was created about agents, transmission modes, epidemiology, treatment, and risk factors for CE. The descriptive survey was performed between May 2015 and May 2016 by face-to-face communication...
March 2018: Saudi Medical Journal
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