1,444,179 results match your criteria Drugs & aging[Journal]


Side Effects of Frequently Used Antihypertensive Drugs on Wound Healing in vitro.

Skin Pharmacol Physiol 2019 Apr 24;32(3):162-172. Epub 2019 Apr 24.

Institute for Translational Wound Research, Centre for Biomedical Education and Research (ZBAF), Witten/Herdecke University, Witten, Germany.

Background: The number of patients who has a daily intake of antihypertensive drugs is rising, due to an also rising prevalence of lifestyle diseases. Interestingly, knowledge about effects of these drugs in terms of wound healing is low.

Objective: Based on a few differing studies, the idea arose that antihypertensives may have side effects on wound healing. Read More

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http://dx.doi.org/10.1159/000499433DOI Listing
April 2019
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Inhibition of Rac1 activity alleviates PM2.5-induced pulmonary inflammation via the AKT signaling pathway.

Toxicol Lett 2019 Apr 21. Epub 2019 Apr 21.

The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China. Electronic address:

PM2.5 is the main particulate air pollutant that is capable of inducing airway injury. Previous studies have indicated that Rac1 is involved in cigarette smoke-induced lung inflammation and lipopolysaccharide-mediated pulmonary injury. Read More

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http://dx.doi.org/10.1016/j.toxlet.2019.04.017DOI Listing

Chemical composition and cytotoxic screening of Musa cavendish green peels extract: Antiproliferative activity by activation of different cellular death types.

Toxicol In Vitro 2019 Apr 21. Epub 2019 Apr 21.

Emergency Medicine Department, Medical School, University of São Paulo, Av. Dr. Arnaldo, 455 - Cerqueira César, São Paulo, São Paulo CEP 01246-903, Brazil.

Musa cavendish, commonly known as banana, is a fruit with nutritional and therapeutic properties. We investigated the chemical composition and in vitro cytotoxic effect of M. cavendish green peel extract (MHE) on cancer cells for the first time. Read More

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http://dx.doi.org/10.1016/j.tiv.2019.04.020DOI Listing

Establishment of Patient-Derived Organoids and Drug Screening for Biliary Tract Carcinoma.

Cell Rep 2019 Apr;27(4):1265-1276.e4

Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.

Biliary tract carcinomas (BTCs) are among the most aggressive malignancies and have a poor prognosis. Here, we successfully established organoid lines derived from intrahepatic cholangiocarcinoma, gallbladder cancer, and neuroendocrine carcinoma of the ampulla of Vater. These organoids derived from BTCs were cultured stably for >1 year and closely recapitulated the histopathology, gene expression, and genetic alterations evident in the primary tumors. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.088DOI Listing

The retinoic acid receptor (RAR) α-specific agonist Am80 (tamibarotene) and other RAR agonists potently inhibit hepatitis B virus transcription from cccDNA.

Antiviral Res 2019 Apr 21. Epub 2019 Apr 21.

University Hospital Heidelberg (Germany), Center for Infectious Diseases, Molecular Virology, Germany; German Center for Infection Research (DZIF), Partner Site Heidelberg, TTU Hepatitis, Germany. Electronic address:

Chronic infection with the human Hepatitis B virus (HBV) is a major global health problem. Hepatitis D virus (HDV) is a satellite of HBV that uses HBV envelope proteins for cell egress and entry. Using infection systems encoding the HBV/HDV receptor human sodium taurocholate co-transporting polypeptide (NTCP), we screened 1181 FDA-approved drugs applying markers for interference for HBV and HDV infection. Read More

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http://dx.doi.org/10.1016/j.antiviral.2019.04.009DOI Listing

Companion diagnostic tests for treatment of lung cancer patients: what are the current and future challenges?

Expert Rev Mol Diagn 2019 Apr 24. Epub 2019 Apr 24.

b Aix Marseille University , CRCM, INSERM, CNRS, AP-HM, Multidisciplinary Oncology and Therapeutic Innovations Department , Chemin des Bourrely, 13015 , Marseille , France .

Introduction: Companion diagnostic tests (CDXs) are considered mandatory for decision making for treatment with targeted therapies in thoracic oncology. The emergence of immunotherapy has also given rise to the development of CDXs. Some CDXs, in particular PD-L1 immunohistochemistry tests, have been questioned and re-examined for use with new combination therapies that are being evaluated in clinical trials. Read More

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http://dx.doi.org/10.1080/14737159.2019.1611426DOI Listing

Fenofibrate -a PPARα agonist- increases alcohol dehydrogenase levels in the liver: implications for its possible use as an ethanol-aversive drug.

Adicciones 2019 Mar 29;0(0):1226. Epub 2019 Mar 29.

Instituto de Ciencias Biomédicas Facultad de Ciencias de la Salud.

After ethanol consumption, disulfiram increases blood-acetaldehyde levels, generating an aversive reaction that deters alcohol drinking. Given the major secondary effects of disulfiram, finding other effective drugs to reduce alcohol consumption in individuals with alcohol-use-disorder is highly desirable. It has been reported that administering fenofibrate to high-drinking rats increases hepatic catalase levels and blood acetaldehyde after administering ethanol and a 60-70% inhibition of voluntary alcohol intake. Read More

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http://dx.doi.org/10.20882/adicciones.1226DOI Listing

Alcohol use and risk factors for self-harm behavior in Spanish adolescents.

Adicciones 2019 Mar 29;0(0):1239. Epub 2019 Mar 29.

Universidad de Oviedo.

Self-harm behaviors in children and adolescents constitute an important public health problem with prevalence figures in the clinical population between 40 and 80%. The objectives of the study were to analyze and compare the Spanish sub-samples of two studies, SEYLE and WE-STAY to determine prevalence, self-harm patterns and factors associated with self-harm behaviors, notably the use of alcohol or drugs. The questionnaires used in both studies were the Global School Health Survey (GSHS), the Beck Depression Inventory (BDI-II), the Strengths and Difficulties Questionnaire (SDQ). Read More

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http://dx.doi.org/10.20882/adicciones.1239DOI Listing

Cell-autonomous and non-autonomous roles of in muscle function and mitochondrial capacity in aging .

Aging (Albany NY) 2019 Apr 24. Epub 2019 Apr 24.

Division of Geriatrics, Gerontology, and Palliative Medicine, Department of Medicine, UTHSCSA, San Antonio, TX 78229, USA.

Sarcopenia, defined as the loss of skeletal muscle mass and strength, contributes to disability and health-related conditions with aging. In vitro studies indicate that age-related mitochondrial dysfunction could play a central role in the development and progression of sarcopenia, but because of limitations in the methods employed, how aging affects muscle mitochondrial function in vivo is not fully understood. We use muscle-targeted fluorescent proteins and the ratiometric ATP reporter, ATeam, to examine changes in muscle mitochondrial mass and morphology, and intracellular ATP levels in . Read More

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http://dx.doi.org/10.18632/aging.101914DOI Listing

The Impact of New Drug Launches on Hospitalization in 2015 for 67 Medical Conditions in 15 OECD Countries: A Two-Way Fixed-Effects Analysis.

Forum Health Econ Policy 2019 Apr 24. Epub 2019 Apr 24.

Columbia University, New York, NY, USA.

There are two types of prescription drug cost offsets. The first type of cost offset - from prescription drug use - is primarily about the effect of changes in drug quantity (e.g. Read More

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http://dx.doi.org/10.1515/fhep-2018-0009DOI Listing

Identification of Novel Phospholipid Transfer Protein Inhibitors by High-Throughput Screening.

SLAS Discov 2019 Apr 24:2472555219842210. Epub 2019 Apr 24.

1 Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Takatsuki, Osaka, Japan.

Atherogenesis has been recognized as a risk factor for lethal cardiovascular diseases. Plasma low-density lipoprotein levels are correlated to the occurrence of atherosclerosis, and their control is critical for both the prevention and treatment of these diseases. Phospholipid transfer protein (PLTP) is one of the key regulators of lipoprotein metabolism; PLTP-deficient mice exhibit decreased apolipoprotein B (apoB)-containing lipoprotein secretion and atherosclerosis, indicating the validity of PLTP as a promising therapeutic target. Read More

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http://dx.doi.org/10.1177/2472555219842210DOI Listing

Polymeric Emulsion Technology Applied to Tretinoin

J Drugs Dermatol 2019 Apr;18(4):s148-154

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Tretinoin Formulation: From Microsponges to Polymeric Emulsion

Authors:
Leon H. Kircik

J Drugs Dermatol 2019 Apr;18(4):s147

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Laser Treatment of Skin of Color for Medical and Aesthetic Uses With a New 650-Microsecond Nd:YAG 1064nm Laser

J Drugs Dermatol 2019 Apr;18(4):s135-137

Individuals with skin of color are a rapidly growing portion of the cosmetic procedures market. There are unique challenges to treating skin conditions in skin of color patients. This article and roundtable discussion focus on the use of energy-based modalities, particularly a 650-microsecond 1064nm laser that delivers energy in a collimated beam. Read More

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Investigation of the effect of P14 promoter aberrant methylation on the biological function of human lung cancer cells.

Thorac Cancer 2019 Apr 24. Epub 2019 Apr 24.

Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.

Background: This study was conducted to investigate the effect of P14 promoter aberrant methylation on the biological function of human lung adenocarcinoma cells.

Methods: We used nested methylation-specific PCR (NMSP) to detect the methylation status of the p14ARF promoter region in SPCA1 and BEAS2B cell lines. The experimental groups were treated with 5-aza-2'-deoxycytidine (5-Aza). Read More

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http://dx.doi.org/10.1111/1759-7714.13082DOI Listing

Simultaneous Analysis of Multiclass Contaminants of Emerging Concern in Sediments by Liquid Chromatography with Tandem Quadrupole Mass Spectrometry.

Environ Toxicol Chem 2019 Apr 24. Epub 2019 Apr 24.

CAS Key Laboratory of Urban Pollutant Conversion, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, China.

A QuEChERS based extraction and simultaneous dispersive solid phase extraction (dSPE) cleanup method was developed for contaminants of emerging concerns (CECs) in sediment samples. Hydration with phosphate buffer (pH 2.0) and salting out with NaCl and MgSO facilitated the extraction and liquid-liquid portioning of the aqueous and organic phases. Read More

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http://dx.doi.org/10.1002/etc.4450DOI Listing
April 2019
3.225 Impact Factor

The effect of diabetes mellitus on pharmacokinetics, pharmacodynamics and adverse drug reactions of anticancer drugs.

J Cell Physiol 2019 Apr 24. Epub 2019 Apr 24.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Diabetes mellitus (DM) and cancer are global problems carrying huge human, social, and economic impact. Type 2 diabetes (T2DM) is associated with an increased risk for a number of cancers, including breast, pancreatic, and liver cancer. Moreover, adverse drug reactions are higher in paitents with cancer with T2DM compared to cancer patients without T2DM. Read More

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http://dx.doi.org/10.1002/jcp.28644DOI Listing

Nevirapine in HIV maintenance therapy - can "old drugs" survive in current HIV management?

Swiss Med Wkly 2019 Apr 24;149:w20053. Epub 2019 Apr 24.

Cantonal Hospital St.Gallen, Department of Infectious Diseases and Hospital Epidemiology, St. Gallen, Switzerland / Children's Hospital of Eastern Switzerland, Department of Infectious Diseases and Hospital Epidemiology, St. Gallen, Switzerland.

Aims Of The Study: Nevirapine has an exceptional record for long-term tolerability with few side effects in human immunodeficiency virus (HIV) combined antiretroviral therapy (cART). Owing to relatively frequent hypersensitivity reactions (HSR) (15–25%) in the first 3 months after treatment initiation (especially in patients with a high CD4 count (>250/µl in women, >400/µl in men)), it is being used less and less. However, the rate of adverse events is lower when patients are already under suppressive cART. Read More

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http://dx.doi.org/10.4414/smw.2019.20053DOI Listing

Childhood epilepsy with a small number of seizures may be left untreated: an international prospective study.

Epileptic Disord 2019 Apr;21(2):141-153

Department of Paediatrics, Dalhousie University and the IWK Health Centre, Halifax, Nova Scotia, Canada.

It is unknown whether treatment with antiepileptic drugs in children with epilepsy with a presumed good prognosis is always necessary. We aimed to study the course of newly diagnosed epilepsy in children with a presumed good prognosis who are managed without AED treatment. A total of 151 children (one month to 12 years of age) with two to five lifetime unprovoked seizures (excluding febrile convulsions), were followed for three years. Read More

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http://dx.doi.org/10.1684/epd.2019.1040DOI Listing

Drug use beyond the licence in palliative care: A systematic review and narrative synthesis.

Palliat Med 2019 Apr 24:269216319840602. Epub 2019 Apr 24.

Department of Palliative Medicine, Ludwig-Maximilians-University Munich, Munich, Germany.

Background: Drug use beyond the licence (off-label use, off-label drug use) is a common practice in palliative care and respective recommendations can often be identified in the literature. It is both risky and offers opportunities at the same time and, therefore, requires special attention in clinical practice.

Aim: To determine the prevalence of off-label drug use in palliative care and to identify, evaluate and critically appraise studies describing the clinical practice, healthcare professionals' awareness, knowledge and attitudes towards off-label-use and management strategies. Read More

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http://dx.doi.org/10.1177/0269216319840602DOI Listing

Quantification of 1D, a novel derivative of curcumin with potential antitumor activity, in rat plasma by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study in rats.

Pharm Biol 2019 Dec;57(1):287-294

a Department of Pharmacy , the Affiliated Hospital of Qingdao University , Qingdao , PR China.

Context: 1 D is a novel derivative of curcumin and shows very promising antitumor activities in various cancer cell lines.

Objective: To characterize its preclinical pharmacokinetic profiles, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of 1 D in rat plasma.

Materials And Methods: An aliquot of 50 μL plasma sample was processed by protein precipitation with methanol. Read More

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http://dx.doi.org/10.1080/13880209.2019.1603243DOI Listing
December 2019

Does choice of antiretroviral drugs matter for inflammation?

Expert Rev Clin Pharmacol 2019 Apr 24:1-8. Epub 2019 Apr 24.

a HIV Infection Unit, Infectious Diseases Department , Hospital de la Santa Creu i Sant Pau Institut de Recerca del Hospital de la Santa Creu i Sant Pau , Barcelona , Spain.

Introduction: The massive implementation of combination antiretroviral therapy (cART) has forever changed the landscape of HIV infection. This unprecedented success has turned HIV infection into a manageable chronic disease. The increased survival of people living with HIV is, however, shadowed by a high burden of aging-related comorbidities. Read More

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http://dx.doi.org/10.1080/17512433.2019.1605902DOI Listing

Discovery, X-ray Crystallography and Antiviral Activity of Allosteric Inhibitors of Flavivirus NS2B-NS3 Protease.

J Am Chem Soc 2019 Apr 23. Epub 2019 Apr 23.

Flaviviruses, including dengue, West Nile and recently emerged Zika virus, are important human pathogens, but there are no drugs to prevent or treat these viral infections. The highly conserved Flavivirus NS2B-NS3 protease is essential for viral replication and therefore a drug target. Compound screening followed by medicinal chemistry yielded a series of drug-like, broadly active inhibitors of Flavivirus proteases with IC as low as 120 nM. Read More

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http://dx.doi.org/10.1021/jacs.9b02505DOI Listing

Successful Treatment of Refractory Plaque-Type Psoriasis and Psoriatic Arthritis With Guselkumab and Adalimumab Combination Therapy: A Case Report

J Drugs Dermatol 2019 Apr;18(4):394-396

Copy: A number of biologics have been approved for use in plaque-type psoriasis. They act by either blocking the action of a specific type of cell or protein in the immune system. Case presentation: Herein, we report a case of a 46-year-old woman with a 12-year history of severe plaque psoriasis and psoriatic arthritis who was treated successfully with guselkumab and adalimumab after failure of prior topical corticosteroids, cyclosporine and narrow-band ultraviolet B (NBUVB) phototherapy. Read More

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Effective delivery of mitomycin-C and meloxicam by double-layer electrospun membranes for the prevention of epidural adhesions.

J Biomed Mater Res B Appl Biomater 2019 Apr 24. Epub 2019 Apr 24.

Beijing Laboratory of Biomedical Materials, State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing, China.

Epidural adhesion between the spinal dura and the surrounding fibrous tissue often occurs post-laminectomy, resulting in clinical symptoms such as nerve compression and severe pain. In this study, we report a drug-loaded double-layered electrospun nanofiber membrane to prevent the occurrence of epidural adhesion. The nanofibers in both layers are made of a mixture of polycaprolactone (PCL) and chitosan (CS) but at different weight ratios. Read More

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http://dx.doi.org/10.1002/jbm.b.34394DOI Listing

Side chain rotameric changes and backbone dynamics enable specific cladosporin binding in Plasmodium falciparum lysyl-tRNA synthetase.

Proteins 2019 Apr 24. Epub 2019 Apr 24.

Structural Parasitology, Molecular Medicine Group, International Center for Genetic Engineering and Biotechnology, New Delhi, India.

Cladosporin (CLD) is a fungal metabolite that kills malaria parasite via inhibiting its cytoplasmic lysyl-tRNA synthetase (KRS) and abrogating protein translation. Here we provide structural and drug selectivity analyses on CLD interacting residues in apo and holo KRSs from Plasmodium falciparum, Homo sapiens, Cryptosporidium parvum and Mycobacterium ulcerans. We show that both gross and subtle alterations in protein backbone and sidechains drive the active site structural plasticity that allows integration of CLD in KRSs. Read More

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http://dx.doi.org/10.1002/prot.25699DOI Listing

Brca1 is involved in tolerance to adefovir dipivoxil‑induced DNA damage.

Int J Mol Med 2019 Jun 11;43(6):2491-2498. Epub 2019 Apr 11.

Department of Pharmacology, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, P.R. China.

Nucleos(t)ide analogues (NAs) are currently the most important anti‑viral treatment option for patients with chronic hepatitis B (CHB). Adefovir dipivoxil (ADV), a diester pro‑drug of adefovir, has been widely used for the clinical therapy of hepatitis B virus infection. It has been previously reported that adefovir induced chromosomal aberrations (CAs) in the in vitro human peripheral blood lymphocyte assay, while the genotoxic mechanism remains elusive. Read More

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http://dx.doi.org/10.3892/ijmm.2019.4164DOI Listing

A Framework for Aiding the Translation of Scientific Evidence into Policy: The Experience of a Hospital-Based Technology Assessment Unit.

Int J Technol Assess Health Care 2019 Apr 24:1-8. Epub 2019 Apr 24.

Technology Assessment Unit,McGill University Health Centre,Montreal,Canada.

Objectives: Very few practical frameworks exist to guide the formulation of recommendations at hospital-based health technology assessment (HTA) units. The objectives of our study were: (i) to identify decision criteria specific to the context of hospital-based health technologies and interventions, (ii) to estimate the extent to which the expert community agrees on the importance of the identified criteria, (iii) to incorporate the identified criteria into a decision-aid tool, and (iv) to illustrate the application of a prototype decision-aid tool.

Methods: Relevant decision criteria were identified using existing frameworks for HTA recommendations, our past experience, a literature search, and feedback from a survey of diverse stakeholders. Read More

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http://dx.doi.org/10.1017/S0266462319000254DOI Listing

A critical review of HPLC-based analytical methods for quantification of Linezolid.

Crit Rev Anal Chem 2019 Apr 24:1-16. Epub 2019 Apr 24.

a Institute of Chemistry, São Paulo State University , Araraquara , Brazil.

Linezolid is a synthetic antimicrobial agent belonging to the oxazolidinone class. Since its approval in the year 2000 until now, linezolid remains the main representative drug for the oxazolidinone class of drugs, which is used in therapy due to its unique mode of action, which involves inhibition of protein synthesis. As linezolid holds great importance in antimicrobial therapy, it is necessary to compile the various analytical methods that have been reported in the literature for its analysis. Read More

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http://dx.doi.org/10.1080/10408347.2019.1605876DOI Listing

[Progress and challenges of global malaria elimination].

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi 2019 Mar;31(1):19-22

WHO Collaborating Center for Research and Training on Malaria Elimination, Key Laboratory of National Health Commission on Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi 214064, China.

Recently, the global malaria control has achieved remarkable results, and the epidemic map of malaria has gradually shrinked. However, in the past two years, the number of malaria deaths remained at a high level, and the incidence of malaria has even risen, leading to the stagnant of malaria elimination. The main reasons include lacking of the well monitoring and response system, sensitivity declining of antimalarial drugs, the spread of insecticide resistance, and the reduction of financial support. Read More

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http://dx.doi.org/10.16250/j.32.1374.2019006DOI Listing

Analysis of Global Drug Development Pathways and Postmarketing Safety in Japan: Local Studies May Reduce Drug-Related Deaths.

Clin Transl Sci 2019 Apr 23. Epub 2019 Apr 23.

Laboratory of Pharmaceutical Regulatory Science, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.

Recent International Conference on Harmonization (ICH) guidelines provide pharmaceutical companies with regulatory justifications to pursue various global drug-development pathways, in some of which "local" dose-ranging and/or pivotal phase III studies are skipped. We examined the association between the clinical development pathway and postmarketing safety in Japan for 177 new molecular entities approved between 2004 and 2013 focusing on dose setting histories for each drug. The risk of drug-related deaths was higher when companies did not conduct local (i. Read More

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http://dx.doi.org/10.1111/cts.12631DOI Listing

Molecular characterization of clinical responses to PD-1/PD-L1 inhibitors in non-small cell lung cancer: Predictive value of multidimensional immunomarker detection for the efficacy of PD-1 inhibitors in Chinese patients.

Thorac Cancer 2019 Apr 23. Epub 2019 Apr 23.

Department of Respiratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China.

According to multiple studies, the objective response rate of PD-1/PD-L1 inhibitors in the second-line treatment of unscreened non-small cell lung cancer (NSCLC) is only approximately 20%. Predictive biomarkers of treatment efficacies are still under investigation. In selected NSCLC patients with PD-L1 expression ≥ 50%, the response rate of pembrolizumab in first-line treatment can reach 44. Read More

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http://dx.doi.org/10.1111/1759-7714.13078DOI Listing

Health effects from unintentional occupational exposure to opioids among law enforcement officers: Two case investigations.

Am J Ind Med 2019 Apr 23. Epub 2019 Apr 23.

National Institute for Occupational Safety and Health, Office of the Director, Washington, District of Columbia.

Recent increases in the rate of drug overdose-related deaths, the emergence of potent opioids such as carfentanil, and media reports of incidents have raised concerns about the potential for work-related exposure to a variety of illicit drugs among law enforcement officers (LEOs), other emergency responders, and other workers in the United States. To characterize the risk associated with unintentional occupational exposure to drugs, we retrospectively investigated two incidents that occurred in 2017 and 2018 where LEOs were exposed to opioid and stimulant drugs and experienced health effects. We interviewed five affected LEOs and others. Read More

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http://dx.doi.org/10.1002/ajim.22967DOI Listing

Enantioseparation of N-acetyl-glutamine enantiomers by LC-MS/MS and its application to plasma protein binding study.

Biomed Chromatogr 2019 Apr 24:e4559. Epub 2019 Apr 24.

Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), China Pharmaceutical University, Nanjing, China.

A novel chiral method was developed and validated to determine N-acetyl-glutamine (NAG) enantiomers by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Enantioseparation was achieved on a CHIRALPAK QD-AX column (150 mm × 4.6 mm ID, 5 μm) using methanol-water (50 mM ammonium formate, pH=4. Read More

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http://dx.doi.org/10.1002/bmc.4559DOI Listing

Effect of Warfarin on Ischemic Stroke, Bleeding, and Mortality in Patients with Atrial Fibrillation Receiving Peritoneal Dialysis.

Am J Cardiovasc Drugs 2019 Apr 23. Epub 2019 Apr 23.

Division of Cardiology, Kaiser Permanente Los Angeles Medical Center, 1526 North Edgemont Street, 2nd Floor, Los Angeles, CA, 90027, USA.

Background: There is limited information on the risks and benefits of anticoagulation in patients with atrial fibrillation receiving peritoneal dialysis.

Objective: The aim was to determine the risk of mortality, ischemic stroke, and bleeding associated with warfarin use in patients with atrial fibrillation receiving peritoneal dialysis.

Patients And Methods: This is a retrospective observational study of a multi-ethnic cohort of patients with atrial fibrillation receiving peritoneal dialysis in the United States. Read More

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http://dx.doi.org/10.1007/s40256-019-00347-3DOI Listing

Carnosic Acid Pretreatment Attenuates Mitochondrial Dysfunction in SH-SY5Y Cells in an Experimental Model of Glutamate-Induced Excitotoxicity.

Neurotox Res 2019 Apr 23. Epub 2019 Apr 23.

Grupo de Estudos em Neuroquímica e Neurobiologia de Moléculas Bioativas, Universidade Federal de Mato Grosso (UFMT), Av. Fernando Corrêa da Costa, 2367, Cuiaba, MT, 78060-900, Brazil.

Mitochondria are the major site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, mitochondria produce most of the reactive oxygen species (ROS) in nucleated cells. Redox and bioenergetic abnormalities have been seen in mitochondria during the onset and progression of neurodegenerative diseases. Read More

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http://dx.doi.org/10.1007/s12640-019-00044-8DOI Listing

Anti-inflammatory Activity of Ursolic Acid in MPTP-Induced Parkinsonian Mouse Model.

Neurotox Res 2019 Apr 23. Epub 2019 Apr 23.

Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, 221005, India.

Neuroinflammation plays an important role in the progression of Parkinson's disease (PD) and hence may represent a target for treatment. The drugs used currently for PD only provide symptomatic relief and have adverse effects in addition to their inability in preventing degeneration of neurons. Flavonoids show potent antioxidant and anti-inflammatory activities which is very valuable for the health of human beings. Read More

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http://dx.doi.org/10.1007/s12640-019-00038-6DOI Listing

Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib.

Clin Pharmacokinet 2019 Apr 23. Epub 2019 Apr 23.

Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, 88397, Biberach an der Riss, Germany.

Nintedanib is an oral, small-molecule tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis and patients with advanced non-small cell cancer of adenocarcinoma tumour histology. Nintedanib competitively binds to the kinase domains of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF). Studies in healthy volunteers and in patients with advanced cancer have shown that nintedanib has time-independent pharmacokinetic characteristics. Read More

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http://dx.doi.org/10.1007/s40262-019-00766-0DOI Listing

Setup and Use of HepaRG Cells in Cholestasis Research.

Methods Mol Biol 2019 ;1981:291-312

INSERM U1241, NuMeCan, Université de Rennes 1, Rennes, France.

Since HepaRG cells can differentiate into well-polarized mature hepatocyte-like cells that synthesize, conjugate, and secrete bile acids, they represent an appropriate surrogate to primary human hepatocytes for investigations on drug-induced cholestasis mechanisms. In this chapter, culture conditions for obtaining HepaRG hepatocytes and the main methods used to detect cholestatic potential of drugs are described. Assays for evaluation of bile canaliculi dynamics and morphology are mainly based on time-lapse and phase-contrast microscopy analysis. Read More

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http://dx.doi.org/10.1007/978-1-4939-9420-5_19DOI Listing
January 2019

Transcriptomic Analysis of Cholestatic Compounds In Vitro.

Methods Mol Biol 2019 ;1981:175-186

KaLy-Cell, Plobsheim, France.

Drug-induced cholestasis is one of the most severe manifestations of drug-induced liver injury. Drug-induced cholestasis is characterized by an accumulation of endogenous metabolites normally excreted in the bile such as bile salts, cholesterol, bilirubin, or drug metabolites. The possibility to determine early in the drug development process whether a compound presents a risk of inducing drug-induced cholestasis is key information. Read More

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http://dx.doi.org/10.1007/978-1-4939-9420-5_12DOI Listing
January 2019

Measuring Apoptosis and Necrosis in Cholestatic Liver Injury.

Methods Mol Biol 2019 ;1981:133-147

Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA.

Cholestasis can be induced by obstruction of bile ducts or intrahepatic toxicity of drugs and chemicals. However, the mode of cell death during cholestasis, i.e. Read More

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http://dx.doi.org/10.1007/978-1-4939-9420-5_9DOI Listing
January 2019

In Vivo Measurement of Hepatic Drug Transporter Inhibition with Radiolabeled Bile Acids.

Methods Mol Biol 2019 ;1981:87-98

Faculty of Pharmaceutical Sciences, Laboratory of Radiopharmacy, Ghent University, Ghent, Belgium.

Drug-induced liver injury, and more specifically drug-induced cholestasis, is responsible for a large amount of hospitalizations and attrition of new drug candidates in preclinical drug development. Drug-induced cholestasis can be triggered by drugs that are inhibitors of the hepatic bile acid transporters. Therefore, it is of considerable interest in preclinical drug development to detect whether new candidate drugs can cause interference with the hepatic bile acid transporters. Read More

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http://dx.doi.org/10.1007/978-1-4939-9420-5_6DOI Listing
January 2019

The C-DILI™ Assay: An Integrated In Vitro Approach to Predict Cholestatic Hepatotoxicity.

Methods Mol Biol 2019 ;1981:75-85

ADME-TOX Division, BioIVT, Durham, NC, USA.

Drug-induced liver injury is an important reason for drug candidate failure. Alterations in the hepatobiliary disposition of bile acids are a proposed mechanism of cholestatic hepatotoxicity. Bile acids are synthesized in the hepatocyte, and excreted into the bile primarily by the bile salt export pump. Read More

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http://dx.doi.org/10.1007/978-1-4939-9420-5_5DOI Listing
January 2019

Mechanisms of Drug-Induced Cholestasis.

Methods Mol Biol 2019 ;1981:1-14

Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Brussels, Belgium.

Cholestasis can be defined as any situation of impaired bile secretion with concomitant accumulation of bile acids in the liver or in the systemic circulation. A variety of factors may evoke cholestasis, including genetic disorders, metabolic pathologies, infectious diseases, immunogenic stimuli, and drugs. Drug-induced cholestasis is a mechanistically complex process. Read More

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http://dx.doi.org/10.1007/978-1-4939-9420-5_1DOI Listing
January 2019
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Role of Probiotics in Eradication Therapy for Helicobacter pylori Infection.

Adv Exp Med Biol 2019 Apr 24. Epub 2019 Apr 24.

Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan.

Probiotics are defined as, "Live microorganisms that, when administered in adequate amounts, confer a health benefit on the host", and have various effects including inhibitory capabilities on pathogens, stimulation of organ functions and activation of immune responses in the human. Probiotics were reported to inhibit Helicobacter pylori not only in vitro, but also in vivo studies. The mechanisms by which probiotics inhibit H. Read More

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http://dx.doi.org/10.1007/5584_2019_369DOI Listing

Safety, Pharmacokinetics, and Pharmacogenetics of Single-Dose Teriflunomide Sodium and Leflunomide in Healthy Chinese Subjects.

Clin Drug Investig 2019 Apr 23. Epub 2019 Apr 23.

Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100032, China.

Background: Teriflunomide sodium, a novel derivative of leflunomide, was developed to treat systemic lupus erythematosus.

Objective: The objectives of this trial were to study the safety, pharmacokinetics, and pharmacogenetics of teriflunomide sodium in healthy Chinese subjects in order to support its accelerated development.

Methods: A clinical study was designed as a single-dose, randomized, parallel, open-label study. Read More

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http://dx.doi.org/10.1007/s40261-019-00786-5DOI Listing

Changing rate of serious infections in biologic-exposed rheumatoid arthritis patients. Data from South American registries BIOBADABRASIL and BIOBADASAR.

Clin Rheumatol 2019 Apr 17. Epub 2019 Apr 17.

Santiago University Clinical Hospital Institute of Medical Research, Santiago de Compostela, Spain.

Objective: Most reports on serious infections (SI) in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) are from the USA and Western Europe. Data from other regions are largely missing. We report data from South American countries with different backgrounds and health-care systems but similar registries. Read More

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http://dx.doi.org/10.1007/s10067-019-04516-2DOI Listing

A Global Phase I Clinical Study Comparing the Safety and Pharmacokinetics of Proposed Biosimilar BAT1706 and Bevacizumab (Avastin) in Healthy Male Subjects.

BioDrugs 2019 Apr 23. Epub 2019 Apr 23.

Bio-Thera Solutions, Ltd., Guangzhou, China.

Objective: BAT1706 is a proposed biosimilar of bevacizumab (BEV). The objective of this phase I clinical trial was to establish pairwise similarity between BAT1706, US-sourced BEV (US-BEV), and EU-sourced BEV (EU-BEV) after a single intravenous (IV) infusion in healthy male subjects.

Methods: This phase I clinical trial was a randomized, double-blinded, three-arm study in 128 healthy adult male subjects. Read More

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http://dx.doi.org/10.1007/s40259-019-00352-7DOI Listing

Efficacy of different analgesic or sedative drug therapies in pediatric patients with congenital heart disease undergoing surgery: a network meta-analysis.

World J Pediatr 2019 Apr 23. Epub 2019 Apr 23.

Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun 130000, China.

Background: Surgery is an effective therapy for congenital heart disease (CHD) and the management after surgery poses challenges for the clinical workers. We performed this network meta-analysis to enhance the corresponding evidence with respect to the relative efficacy of different drug treatments applied after the CHD surgery.

Methods: Embase and PubMed were systematically retrieved to identify all published controlled trials investigating the effectiveness of drugs for patients up to 25 August, 2018. Read More

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http://dx.doi.org/10.1007/s12519-019-00252-4DOI Listing

Real World Evidence: Can We Really Expect It to Have Much Influence?

Authors:
Keith Evans

Drugs Real World Outcomes 2019 Apr 23. Epub 2019 Apr 23.

Global Health Outcomes, InScience Communications, Springer Healthcare Ltd., Chester, UK.

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http://dx.doi.org/10.1007/s40801-019-0155-3DOI Listing
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