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https://www.readbyqxmd.com/read/28346841/rapid-and-reliable-genotyping-of-hla-b-57-01-in-four-chinese-populations-using-a-single-tube-duplex-real-time-polymerase-chain-reaction-assay
#1
Min Han, Xing Kang, Zhengbin Liu, Tingting Zhang, Yanwei Li, Chao Chen, Huijuan Wang
HLA-B*57:01 is strongly associated with severe adverse drug reaction induced by the anti-HIV drug abacavir (ABC) and antibiotic flucloxacillin. This study was dedicated to establishing a new method for HLA-B*57:01 genotyping and investigating the HLA-B*57:01 distribution pattern in four Chinese populations. A single-tube duplex real-time polymerase chain reaction (PCR) system was established by combining the amplification refractory mutation system and TaqMan probe. The reliability of this assay was validated by comparing the genotyping results with those by sequence-based typing...
March 27, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28346810/an-automated-multiplexed-hepatotoxicity-and-cyp-induction-assay-using-heparg-cells-in-2d-and-3d
#2
Lindsey M Ott, Karthik Ramachandran, Lisa Stehno-Bittel
Drug-induced liver injury (DILI) and drug-drug interactions (DDIs) are concerns when developing safe and efficacious compounds. We have developed an automated multiplex assay to detect hepatotoxicity (i.e., ATP depletion) and metabolism (i.e., cytochrome P450 1A [CYP1A] and cytochrome P450 3A4 [CYP3A4] enzyme activity) in two-dimensional (2D) and three-dimensional (3D) cell cultures. HepaRG cells were cultured in our proprietary micromold plates and produced spheroids. HepaRG cells, in 2D or 3D, expressed liver-specific proteins throughout the culture period, although 3D cultures consistently exhibited higher albumin secretion and CYP1A/CYP3A4 enzyme activity than 2D cultures...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346693/using-a-novel-nqo1-bioactivatable-drug-beta-lapachone-arq761-to-enhance-chemotherapeutic-effects-by-metabolic-modulation-in-pancreatic-cancer
#3
Muhammad Shaalan Beg, Xiumei Huang, Molly A Silvers, David E Gerber, Joyce Bolluyt, Venetia Sarode, Farjana Fattah, Ralph J Deberardinis, Matthew E Merritt, Xian-Jin Xie, Richard Leff, Daniel Laheru, David A Boothman
Novel, tumor-selective therapies are needed to increase the survival rate of pancreatic cancer patients. K-Ras-mutant-driven NAD(P)H:quinone oxidoreductase 1 (NQO1) is over-expressed in pancreatic tumor versus associated normal tissue, while catalase expression is lowered compared to levels in associated normal pancreas tissue. ARQ761 undergoes a robust, futile redox cycle in NQO1+ cancer cells, producing massive hydrogen peroxide (H2 O2 ) levels; normal tissues are spared by low NQO1 and high catalase expression...
March 27, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28346645/facial-trauma-caused-by-electronic-cigarette-explosion
#4
Brian Vaught, Joseph Spellman, Anil Shah, Alexander Stewart, David Mullin
Electronic cigarettes are increasingly popular as a supposed safer alternative to tobacco cigarettes or a smoking cessation tool. Research and debate have focused primarily on possible adverse effects caused by the inhaled aerosol produced by electronic cigarettes and on smoking cessation efficacy. Few reports in the medical literature describe injuries secondary to device malfunction. We present a case of electronic cigarette explosion, with a projectile fracturing the patient's right naso-orbital-ethmoid complex and anterior and posterior frontal sinus tables, with frontal sinus outflow tract involvement...
March 2017: Ear, Nose, & Throat Journal
https://www.readbyqxmd.com/read/28346597/association-of-risk-of-viremia-immunosuppression-serious-clinical-events-and-mortality-with-increasing-age-in-perinatally-human-immunodeficiency-virus-infected-youth
#5
Anne M Neilan, Brad Karalius, Kunjal Patel, Russell B Van Dyke, Mark J Abzug, Allison L Agwu, Paige L Williams, Murli Purswani, Deborah Kacanek, James M Oleske, Sandra K Burchett, Andrew Wiznia, Miriam Chernoff, George R Seage, Andrea L Ciaranello
Importance: As perinatally human immunodeficiency virus-infected youth (PHIVY) in the United States grow older and more treatment experienced, clinicians need updated information about the association of age, CD4 cell count, viral load (VL), and antiretroviral (ARV) drug use with risk of opportunistic infections, key clinical events, and mortality to understand patient risks and improve care. Objective: To examine the incidence or first occurrence during follow-up of key clinical events (including Centers for Disease Control and Prevention stage B [CDC-B] and stage C [CDC-C] events) and mortality among PHIVY stratified by age, CD4 cell count, and VL and ARV status...
March 27, 2017: JAMA Pediatrics
https://www.readbyqxmd.com/read/28346428/autophagy-is-required-for-cell-survival-under-l-asparaginase-induced-metabolic-stress-in-acute-lymphoblastic-leukemia-cells
#6
H Takahashi, J Inoue, K Sakaguchi, M Takagi, S Mizutani, J Inazawa
L-asparaginase has been used for more than three decades in acute lymphoblastic leukemia (ALL) patients and remains an essential drug in the treatment of ALL. Poor response to L-asparaginase is associated with increased risk of therapeutic failure in ALL. However, both the metabolic perturbation and molecular context of L-asparaginase-treated ALL cells has not been fully elucidated. Here we identify that treatment with L-asparaginase results in metabolic shutdown via the reduction of both glycolysis and oxidative phosphorylation, accompanied by mitochondrial damage and activation of autophagy...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28346390/the-effect-and-mechanism-of-transdermal-penetration-enhancement-of-fu-s-cupping-therapy-new-physical-penetration-technology-for-transdermal-administration-with-traditional-chinese-medicine-tcm-characteristics
#7
Wei-Jie Xie, Yong-Ping Zhang, Jian Xu, Xiao-Bo Sun, Fang-Fang Yang
BACKGROUND: In this paper, a new type of physical penetration technology for transdermal administration with traditional Chinese medicine (TCM) characteristics is presented. Fu's cupping therapy (FCT), was established and studied using in vitro and in vivo experiments and the penetration effect and mechanism of FCT physical penetration technology was preliminarily discussed. METHODS: With 1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-ylacetic acid (indomethacin, IM) as a model drug, the establishment of high, medium, and low references was completed for the chemical permeation system via in vitro transdermal tests...
March 27, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28346347/biosynthesis-of-%C3%AE-glucosidase-inhibitors-by-a-newly-isolated-bacterium-paenibacillus-sp-tku042-and-its-effect-on-reducing-plasma-glucose-in-a-mouse-model
#8
Van Bon Nguyen, Anh Dzung Nguyen, Yao-Haur Kuo, San-Lang Wang
Paenibacillus sp. TKU042, a bacterium isolated from Taiwanese soil, produced α-glucosidase inhibitors (aGIs) in the culture supernatant when commercial nutrient broth (NB) was used as the medium for fermentation. The supernatant of fermented NB (FNB) showed stronger inhibitory activities than acarbose, a commercial anti-diabetic drug. The IC50 and maximum α-glucosidase inhibitory activities (aGIA) of FNB and acarbose against α-glucosidase were 81 μg/mL, 92% and 1395 μg/mL, 63%, respectively. FNB was found to be strongly thermostable, retaining 95% of its relative activity, even after heating at 100 °C for 30 min...
March 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28346238/management-of-hypertension-in-2017-targets-and-therapies
#9
Monica Ahluwalia, Sripal Bangalore
PURPOSE OF REVIEW: Approximately one-fourth of the adult population is diagnosed with hypertension, which has been associated with increased cardiovascular morbidity and mortality including cardiovascular death, myocardial infarction, heart failure and stroke. Early detection and treatment is a key and can lead to a significant reduction in cardiovascular morbidity and mortality. RECENT FINDINGS: In this review, we discuss the management and treatment strategies in patients with hypertension in the current era...
March 24, 2017: Current Opinion in Cardiology
https://www.readbyqxmd.com/read/28346229/clinical-efficacy-of-gene-modified-stem-cells-in-adenosine-deaminase-deficient-immunodeficiency
#10
Kit L Shaw, Elizabeth Garabedian, Suparna Mishra, Provaboti Barman, Alejandra Davila, Denise Carbonaro, Sally Shupien, Christopher Silvin, Sabine Geiger, Barbara Nowicki, E Monika Smogorzewska, Berkley Brown, Xiaoyan Wang, Satiro de Oliveira, Yeong Choi, Alan Ikeda, Dayna Terrazas, Pei-Yu Fu, Allen Yu, Beatriz Campo Fernandez, Aaron R Cooper, Barbara Engel, Greg Podsakoff, Arumugam Balamurugan, Stacie Anderson, Linda Muul, G Jayashree Jagadeesh, Neena Kapoor, John Tse, Theodore B Moore, Ken Purdy, Radha Rishi, Kathey Mohan, Suzanne Skoda-Smith, David Buchbinder, Roshini S Abraham, Andrew Scharenberg, Otto O Yang, Kenneth Cornetta, David Gjertson, Michael Hershfield, Rob Sokolic, Fabio Candotti, Donald B Kohn
BACKGROUND: Autologous hematopoietic stem cell transplantation (HSCT) of gene-modified cells is an alternative to enzyme replacement therapy (ERT) and allogeneic HSCT that has shown clinical benefit for adenosine deaminase-deficient (ADA-deficient) SCID when combined with reduced intensity conditioning (RIC) and ERT cessation. Clinical safety and therapeutic efficacy were evaluated in a phase II study. METHODS: Ten subjects with confirmed ADA-deficient SCID and no available matched sibling or family donor were enrolled between 2009 and 2012 and received transplantation with autologous hematopoietic CD34+ cells that were modified with the human ADA cDNA (MND-ADA) γ-retroviral vector after conditioning with busulfan (90 mg/m2) and ERT cessation...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28346213/development-and-application-of-a-high-performance-liquid-chromatography-stability-indicating-assay-for-beyond-use-date-determination-of-compounded-topical-gels-containing-multiple-active-drugs
#11
Gregory Gorman, Simara Sokom, Lori Coward, John J Arnold
Topical gels compounded by pharmacists are important clinical tools for the management of pain. Nevertheless, there is often a dearth of information about the chemical stability of drugs included in these topical formulations, complicating the assignment of beyond-use dating. The purpose of this study was to develop a high-performance liquid chromatography photodiode array-based stability-indicating assay that could simultaneously resolve six drugs (amitriptyline, baclofen, clonidine, gabapentin, ketoprofen, lidocaine) commonly included in topical gels for pain management and their potential degradation products...
March 2017: International Journal of Pharmaceutical Compounding
https://www.readbyqxmd.com/read/28346200/compatibility-and-stability-of-rolapitrant-injectable-emulsion-admixed-with-intravenous-palonsetron-hydrochloride
#12
George Wu, Stanley Yeung, Frank Chen
Neurokinin-1 receptor antagonist, 5-hydroxytryptamine-3 RA, and dexamethasone combination therapy is standard of care for the prevention of chemotherapy-induced nausea and vomiting. Herein we describe the physical and chemical stability of rolapitant injectable emulsion 166.5 mg in 92.5 mL (185 mg hydrochloride salt) admixed with palonosetron injection 0.25 mg in 5 mL (0.28 mg hydrochloride salt). Admixtures were prepared and stored in two types of container closures (110-mL Crystal Zenith plastic and glass bottles) and four types of intravenous administration sets (or intravenous tubing sets)...
January 2017: International Journal of Pharmaceutical Compounding
https://www.readbyqxmd.com/read/28346199/compatibility-and-stability-of-rolapitant-injectable-emulsion-admixed-with-dexamethasone-sodium-phosphate
#13
George Wu, Stanley Yeung, Frank Chen
Neurokinin-1 receptor antagonist, 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone combination therapy is the standard of care for the prevention of chemotherapy-induced nausea and vomiting. Herein, we describe the physical and chemical stability of an injectable emulsion of the Neurokinin-1 receptor antagonist rolapitant 185 mg in 92.5 mL (free base, 166.5 mg in 92.5 mL) admixed with either 2.5 mL of dexamethasone sodium phosphate (10 mg) or 5 mL of dexamethasone sodium phosphate (20 mg). Admixtures were prepared and stored in two types of container closures (glass and Crystal Zenith plastic bottles) and four types of intravenous administration tubing sets (or intravenous tubing sets)...
January 2017: International Journal of Pharmaceutical Compounding
https://www.readbyqxmd.com/read/28346097/an-optimized-3d-coculture-assay-for-preclinical-testing-of-pro-and-antiangiogenic-drugs
#14
Daniela Unterleuthner, Nina Kramer, Karoline Pudelko, Alexandra Burian, Markus Hengstschläger, Helmut Dolznig
Angiogenesis is a promising target for anticancer therapies, but also for treating other diseases with pathologic vessel development. Targeting the vascular endothelial growth factor (VEGF) pathway did not proof as effective as expected due to emerging intrinsic resistance mechanisms, as well as stromal contributions leading to drug insensitivity. Therefore, alternative strategies affecting the interaction of endothelial cells (ECs) with other stromal cells seem to be more promising. Human preclinical in vitro angiogenesis models successfully recapitulating these interactions are rare, and two-dimensional (2D) cell cultures cannot mimic tissue architecture in vivo...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346096/a-novel-multiparametric-drug-scoring-method-for-high-throughput-screening-of-3d-multicellular-tumor-spheroids-using-the-celigo-image-cytometer
#15
Scott Cribbes, Sarah Kessel, Scott McMenemy, Jean Qiu, Leo Li-Ying Chan
Three-dimensional (3D) tumor models have been increasingly used to investigate and characterize cancer drug compounds. The ability to perform high-throughput screening of 3D multicellular tumor spheroids (MCTS) can highly improve the efficiency and cost-effectiveness of discovering potential cancer drug candidates. Previously, the Celigo Image Cytometer has demonstrated a novel method for high-throughput screening of 3D multicellular tumor spheroids. In this work, we employed the Celigo Image Cytometer to examine the effects of 14 cancer drug compounds on 3D MCTS of the glioblastoma cell line U87MG in 384-well plates...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346090/identifying-inhibitors-of-the-hsp90-aha1-protein-complex-a-potential-target-to-drug-cystic-fibrosis-by-alpha-technology
#16
Verena Ihrig, Wolfgang M J Obermann
Deletion of a single phenylalanine residue at position 508 of the protein CFTR (cystic fibrosis transmembrane conductance regulator), a chloride channel in lung epithelium, is the most common cause for cystic fibrosis. As a consequence, folding of the CFTRΔF508 protein and delivery to the cell surface are compromised, resulting in degradation of the polypeptide. Accordingly, decreased surface presence of CFTRΔF508 causes impaired chloride ion conductivity and is associated with mucus accumulation, a hallmark of cystic fibrosis...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346039/comparison-between-urinalysis-results-and-self-reported-heroin-use-among-patients-undergoing-methadone-maintenance-treatment-in-china
#17
Li Li, Li-Jung Liang, Chunqing Lin, Nan Feng, Zunyou Wu
BACKGROUND: The validity and concordance of two main measures of drug use behavior, self-report and urinalysis, has long been discussed. More understanding is needed about the underlying factors associated with discordance between these two methods. OBJECTIVES: Describe the pattern and associated factors of discordance between self-reported heroin use and the urinalysis results of opiate use among methadone maintenance therapy (MMT) patients in China. METHODS: A total of 2,448 MMT patients from 68 clinics in five provinces of China participated in a survey, which collected information on demographics, drug use and MMT-related factors, depressive symptoms, and drug avoidance self-efficacy...
March 27, 2017: Substance Use & Misuse
https://www.readbyqxmd.com/read/28346018/antiretroviral-treatment-in-hiv-infected-children-who-require-a-rifamycin-containing-regimen-for-tuberculosis
#18
Helena Rabie, Eric H Decloedt, Anthony J Garcia-Prats, Mark F Cotton, Lisa Frigati, Marc Lallemant, Anneke Hesseling, H Simon Schaaf
In high prevalence settings, tuberculosis and HIV dual infection and co-treatment is frequent. Rifamycins, especially rifampicin, in combination with isoniazid, ethambutol and pyrazinamide are key components of short-course antituberculosis therapy. Areas covered: We reviewed available data, for which articles were identified by a Pubmed search, on rifamycin-antiretroviral interactions in HIV-infected children. Rifamycins have potent inducing effects on phase I and II drug metabolising enzymes and transporters...
March 27, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28346011/various-plus-unique-viral-protein-u-as-a-plurifunctional-protein-for-hiv-1-replication
#19
Andrew Soper, Guillermo Juarez-Fernandez, Hirofumi Aso, Miyu Moriwaki, Eri Yamada, Yusuke Nakano, Yoshio Koyanagi, Kei Sato
Human immunodeficiency virus type 1 (HIV-1), the causative agent of acquired immunodeficiency syndrome, encodes four accessory genes, one of which is viral protein U (Vpu). Recently, the study of Vpu has been of great interest. For instance, various cellular proteins are degraded (e.g. CD4) and down-modulated (e.g. tetherin) by Vpu. Vpu also antagonizes the function of tetherin and inhibits NF-κB. Moreover, Vpu is a viroporin forming ion channels and may represent a promising target for anti-HIV-1 drugs. In this review, we summarize the domains/residues that are responsible for Vpu's functions, describe the current understanding of the role of Vpu in HIV-1-infected cells, and review the effect of Vpu on HIV-1 in replication and pathogenesis...
April 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28345746/an-analysis-of-errors-discrepancies-and-variation-in-opioid-prescriptions-for-adult-outpatients-at-a-teaching-hospital
#20
Mark C Bicket, Deepa Kattail, Myron Yaster, Christopher L Wu, Peter Pronovost
OBJECTIVE: To determine opioid-prescribing patterns and rate of three types of errors, discrepancies, and variation from ideal practice. DESIGN: Retrospective review of opioid prescriptions processed at an outpatient pharmacy. SETTING: Tertiary institutional medical center. PATIENTS: We examined 510 consecutive opioid medication prescriptions for adult patients processed at an institutional outpatient pharmacy in June 2016 for patient, provider, and prescription characteristics...
January 2017: Journal of Opioid Management
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