5,480,351 results match your criteria Drug metabolism and disposition: the biological fate of chemicals[Journal]

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MiR-16-1-3p and miR-16-2-3p possess strong tumor suppressive and anti-metastatic properties in osteosarcoma.

Int J Cancer 2019 Apr 24. Epub 2019 Apr 24.

The Lautenberg Center for General and Tumor Immunology, Department of Immunology and Cancer Research-IMRIC, The Hebrew University-Hadassah Medical School at Ein-Kerem, Jerusalem, Israel.

Osteosarcoma (OS) is an aggressive malignancy affecting mostly children and adolescents. MicroRNAs (miRNAs) play important roles in OS development and progression. Here we found that miR-16-1-3p and miR-16-2-3p "passenger" strands as well as the "lead" miR-16-5p strand are frequently downregulated and possess strong tumor suppressive functions in human OS. Read More

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http://dx.doi.org/10.1002/ijc.32368DOI Listing

Systemic Treatment Options for Carcinoid Syndrome: A Systematic Review.

Oncology 2019 Apr 24:1-17. Epub 2019 Apr 24.

Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA.

Background: Carcinoid syndrome symptoms significantly reduce quality of life in patients with neuroendocrine tumors. Evidence supporting the use of somatostatin analogues in carcinoid syndrome symptom control dates back 30 years. The introduction of new treatment options for carcinoid syndrome, such as telotristat ethyl in 2017, highlights the need for a review of high-level evidence of new and established systemic treatments. Read More

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http://dx.doi.org/10.1159/000499049DOI Listing

No Difference in Prevalence of Transmitted Drug Resistance between Injection Drug Users and Non-Injection Drug Users: A Cross-Sectional Study among Antiretroviral Treatment-Naïve HIV Patients.

Intervirology 2019 Apr 24:1-11. Epub 2019 Apr 24.

Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, China,

Objectives: The epidemiological evidence is inconsistent about whether HIV-positive injection drug users (IDUs) are at higher risk of developing antiretroviral resistance than any other HIV-positive populations. This study aims to investigate and compare transmitted drug resistance (TDR) between IDUs and non-IDUs in Lingshan County, an HIV-hit region in Guangxi, China, where IDU and heterosexual transmission were the two dominant transmission routes and roughly equally contributed to the local HIV transmission.

Methods: A cross-sectional study was conducted among newly diagnosed and antiretroviral-treatment (ART)-naïve HIV-1 patients from Lingshan County. Read More

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https://www.karger.com/Article/FullText/499367
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http://dx.doi.org/10.1159/000499367DOI Listing
April 2019
5 Reads

Schiff-base reaction induced selective sensing of trace dopamine based on Pt41Rh59 alloy/ZIF-90 nanocomposite.

Nanotechnology 2019 Apr 24. Epub 2019 Apr 24.

Department of Physics, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, HONG KONG.

Zeolitic imidazole frameworks (ZIFs) are a new class of functional porous materials with attractive characters, such as gas storage, selective separation, catalysis, and drug delivery. We report herein using nanoscale ZIF-90 crystals with free aldehyde group of imidazole-2-carboxaldehyde (ICA) ligand for the selective electrochemical detection of dopamine. The averaged adsorption enthalpy ΔH (i. Read More

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http://dx.doi.org/10.1088/1361-6528/ab1bfbDOI Listing

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

Analgesic and anti-inflammatory effects and molecular mechanisms of Kadsura heteroclita stems, an anti-arthritic Chinese Tujia ethnomedicinal herb.

J Ethnopharmacol 2019 Apr 21:111902. Epub 2019 Apr 21.

TCM and Ethnomedicine Innovation & Development International Laboratory, Innovative Materia Medica Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, PR China. Electronic address:

Ethnopharmacological Relevance: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by failure of spontaneous resolution of inflammation. The stem of Kadsura heteroclite (KHS) is a well-known anti-arthritic Tujia ethnomedicinal plant, which named Xuetong in folk, has long been used for the prevention and treatment of rheumatic and arthritic diseases.

Aim Of The Study: The analgesic and anti-inflammatory effects and the potential mechanisms behind such effects of KHS would be investigated by using different animal models. Read More

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http://dx.doi.org/10.1016/j.jep.2019.111902DOI Listing

Single-Cell Transcriptomics Analyses of Neural Stem Cell Heterogeneity and Contextual Plasticity in a Zebrafish Brain Model of Amyloid Toxicity.

Cell Rep 2019 Apr;27(4):1307-1318.e3

Kizil Lab, German Center for Neurodegenerative Diseases (DZNE) Dresden, Helmholtz Association, Tatzberg 41, 01307 Dresden, Germany; Kizil Lab, Technische Universität Dresden, Center for Regenerative Therapies Dresden (CRTD), Fetscherstr. 105, 01307 Dresden, Germany. Electronic address:

The neural stem cell (NSC) reservoir can be harnessed for stem cell-based regenerative therapies. Zebrafish remarkably regenerate their brain by inducing NSC plasticity in a Amyloid-β-42 (Aβ42)-induced experimental Alzheimer's disease (AD) model. Interleukin-4 (IL-4) is also critical for AD-induced NSC proliferation. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.090DOI 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

Development of a Cx46 Targeting Strategy for Cancer Stem Cells.

Cell Rep 2019 Apr;27(4):1062-1072.e5

Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address:

Gap-junction-mediated cell-cell communication enables tumor cells to synchronize complex processes. We previously found that glioblastoma cancer stem cells (CSCs) express higher levels of the gap junction protein Cx46 compared to non-stem tumor cells (non-CSCs) and that this was necessary and sufficient for CSC maintenance. To understand the mechanism underlying this requirement, we use point mutants to disrupt specific functions of Cx46 and find that Cx46-mediated gap-junction coupling is critical for CSCs. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22111247193041
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http://dx.doi.org/10.1016/j.celrep.2019.03.079DOI Listing
April 2019
1 Read

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

Gold Cube-in-Cube Based Oxygen Nanogenerator: A Theranostic Nanoplatform for Modulating Tumor Microenvironment for Precise Chemo-Phototherapy and Multimodal Imaging.

ACS Nano 2019 Apr 24. Epub 2019 Apr 24.

Engineering a versatile oncotherapy nanoplatform integrating both diagnostic and therapeutic functions has always been an intractable challenge in targeted cancer treatment. Herein, to actualize the theme of precise medicine, a nanoplatform is developed by anchoring Mn-Cdots to doxorubicin (DOX)-loaded mesoporous silica-coated gold cube-in-cubes core/shell nanocomposites and further conjugating them to a Arg-Gly-Asp (RGD) peptide (denoted as RGD-CCmMC/DOX) to achieve active-targeting effect. Under a 635 nm irradiation, the nanoplatform acts as oxygen nanogenerator that produces O2 in situ and amplifies the content of singlet oxygen (1O2) in the hypoxic tumor microenvironment (TME), which has been demonstrated to attenuate tumor hypoxia and synchronously enhance photodynamic efficacy. Read More

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http://dx.doi.org/10.1021/acsnano.8b09786DOI Listing
April 2019
3 Reads

Stomaching Drug Delivery.

N Engl J Med 2019 04;380(17):1671-1673

From the School of Veterinary Medicine and Conway Institute of Biotechnology, University College Dublin, Dublin.

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http://dx.doi.org/10.1056/NEJMcibr1901766DOI Listing

Mesenchymal Stem Cell Capping on ECM-Anchored Caspase Inhibitor-Loaded PLGA Microspheres for Intraperitoneal Injection in DSS-Induced Murine Colitis.

Small 2019 Apr 24:e1901269. Epub 2019 Apr 24.

College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk, 38541, Republic of Korea.

Mesenchymal stem cells (MSCs) are considered as a promising alternative for the treatment of various inflammatory disorders. However, poor viability and engraftment of MSCs after transplantation are major hurdles in mesenchymal stem cell therapy. Extracellular matrix (ECM)-coated scaffolds provide better cell attachment and mechanical support for MSCs after transplantation. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.2019012
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http://dx.doi.org/10.1002/smll.201901269DOI Listing
April 2019
1 Read

Bioinspired Multivalent Peptide Nanotubes for Sialic Acid Targeting and Imaging-Guided Treatment of Metastatic Melanoma.

Small 2019 Apr 24:e1900157. Epub 2019 Apr 24.

School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200241, China.

Tumor metastasis is considered a major cause of cancer-related human mortalities. However, it still remains a formidable challenge in clinics. Herein, a bioinspired multivalent nanoplatform for the highly effective treatment of the metastatic melanoma is reported. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.2019001
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http://dx.doi.org/10.1002/smll.201900157DOI Listing
April 2019
1 Read

A Diene-Containing Noncanonical Amino Acid Enables Dual Functionality in Proteins: Rapid Diels-Alder Reaction with Maleimide or Proximity-Based Dimerization.

Angew Chem Int Ed Engl 2019 Apr 24. Epub 2019 Apr 24.

AstraZeneca, Antibody Discovery and Protein Engineering, 1 MedImmune Way, 20878, Gaithersburg, UNITED STATES.

Here, we describe a diene-containing noncanonical amino acid (ncAA) capable of undergoing fast and selective normal electron-demand Diels-Alder (DA) reactions following its incorporation into antibodies. A cyclopentadiene derivative of lysine (CpHK) served as the reactive handle for DA transformations and the substrate for genetic incorporation. CpHK incorporated into antibodies with high efficiency and was available for maleimide conjugation or self-reaction depending on position in the amino acid sequence. Read More

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http://dx.doi.org/10.1002/anie.201903494DOI Listing

What to do when drivers test positive for methadone in roadside drug tests? The Spanish Experience.

Adicciones 2019 Mar 27;0(0):1249. Epub 2019 Mar 27.

Universidad de Valladolid. Hospital Virgen de la Concha, Zamora..

Letter to the editor. Read More

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http://dx.doi.org/10.20882/adicciones.1249DOI 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

The negative allosteric modulator of mGluR5, MPEP, potentiates the rewarding properties of cocaine in priming-induced reinstatement of CPP.

Adicciones 2019 Mar 28;0(0):1156. Epub 2019 Mar 28.

Universitat de València.

Cocaine addiction is a chronic disorder with high relapse rates; therefore, understanding the neuronal mechanisms underlying drug-seeking during relapse is a priority to develop targeted pharmacotherapy. The metabotropic glutamate receptor 5 (mGluR5) seems to be involved in the reinstatement induced by cocaine-associated cues. The main objective of the study was to evaluate the efficacy of MPEP, a negative allosteric modulator of mGluR5, in attenuating or potentiating the reinstatement induced by priming doses of cocaine in the CPP paradigm, ultimately to further knowledge regarding the role of the mGluR5 in relapse into cocaine abuse. Read More

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http://dx.doi.org/10.20882/adicciones.1156DOI Listing

A context-based ABC model for literature-based discovery.

PLoS One 2019 24;14(4):e0215313. Epub 2019 Apr 24.

Department of Library and Information Science, Yonsei University, Seoul, Korea.

Background: In the literature-based discovery, considerable research has been done based on the ABC model developed by Swanson. ABC model hypothesizes that there is a meaningful relation between entity A extracted from document set 1 and entity C extracted from document set 2 through B entities that appear commonly in both document sets. The results of ABC model are relations among entity A, B, and C, which is referred as paths. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215313PLOS
April 2019
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Methanol stem bark extract of Adansonia digitata ameliorates chronic unpredictable mild stress-induced depression-like behavior: Involvement of the HPA axis, BDNF, and stress biomarkers pathways.

J Basic Clin Physiol Pharmacol 2019 Apr 24. Epub 2019 Apr 24.

Department of Pharmacognosy and Drug Development, Ahmadu Bello University, Zaria, Nigeria.

Background Adansonia digitata L. (Malvaceae) is used locally in the management of depressive illnesses, and its antidepressant-like effect has been previously reported. The present study was aimed at determining the effect of the methanol extract of the stem bark of A. Read More

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http://dx.doi.org/10.1515/jbcpp-2018-0153DOI 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

Increase in Drug Spending in Canada Due to Extension of Data Protection for Biologics: A Descriptive Study.

Authors:
Joel Lexchin

Healthc Policy 2019 Feb;14(3):10-18

Professor Emeritus, School of Health Policy and Management, York University, Emergency Physician, University Health Network, Associate Professor, Faculty of Medicine, University of Toronto, Toronto, ON.

Introduction: Biologics are currently protected from competition by eight years of data protection. The renegotiated North American Free Trade Agreement (NAFTA) increases data protection from 8 to 10 years. This study investigates the effect of such an extension on drug spending in Canada. Read More

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http://dx.doi.org/10.12927/hcpol.2019.25796DOI Listing
February 2019

Transfer of Cyclobenzaprine into Human Milk and Subsequent Infant Exposure.

J Hum Lact 2019 Apr 24:890334419843307. Epub 2019 Apr 24.

2 Department of Pediatrics, Texas Tech University Health Sciences Center, Amarillo, TX, USA.

Background: Cyclobenzaprine is a skeletal muscle relaxant primarily used in the treatment of pain. Its use during lactation is a matter of concern as its level of exposure to infants through human milk is still unknown.

Research Aim: The aim of this study was to determine cyclobenzaprine concentrations in the milk samples collected from two lactating mothers. Read More

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http://dx.doi.org/10.1177/0890334419843307DOI Listing

A General TR-FRET Assay Platform for High-Throughput Screening and Characterizing Inhibitors of Methyl-Lysine Reader Proteins.

SLAS Discov 2019 Apr 24:2472555219844569. Epub 2019 Apr 24.

2 Center for Integrative Chemical Biology and Drug Discovery, Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Chromatin regulatory complexes localize to specific sites via recognition of posttranslational modifications (PTMs) on N-terminal tails of histone proteins (e.g., methylation, acetylation, and phosphorylation). Read More

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http://dx.doi.org/10.1177/2472555219844569DOI Listing

Comprehensive Study of the Proteome and Transcriptome of the Venom of the Most Venomous European Viper: Discovery of a New Subclass of Ancestral Snake Venom Metalloproteinase Precursor-Derived Proteins.

J Proteome Res 2019 Apr 24. Epub 2019 Apr 24.

Department of Molecular and Biomedical Sciences , Jožef Stefan Institute , Jamova cesta 39 , SI-1000 Ljubljana , Slovenia.

The nose-horned viper, its nominotypical subspecies Vipera ammodytes ammodytes ( Vaa), in particular, is, medically, one of the most relevant snakes in Europe. The local and systemic clinical manifestations of poisoning by the venom of this snake are the result of the pathophysiological effects inflicted by enzymatic and nonenzymatic venom components acting, most prominently, on the blood, cardiovascular, and nerve systems. This venom is a very complex mixture of pharmacologically active proteins and peptides. Read More

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http://dx.doi.org/10.1021/acs.jproteome.9b00120DOI Listing

The Mosaic of Rottlerin: The Sequel.

J Nat Prod 2019 Apr 24. Epub 2019 Apr 24.

School of Chemistry , UNSW Australia , Sydney , NSW 2052 , Australia.

Rottlerin (1) is a potent protein kinase C δ inhibitor that possesses a wide range of biological activities. However, the potential of this molecule to be developed as a drug has been restricted by its limited availability. We report herein a gram scale quantity synthesis of rottlerin in a five-step synthetic route that can be completed within 2 days. Read More

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http://dx.doi.org/10.1021/acs.jnatprod.8b00917DOI Listing
April 2019
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A NIR-activated Polymeric Nanoplatform with Upper Critical Solution Temperature for Image-guided Synergistic Photothermal and Chemotherapy.

Biomacromolecules 2019 Apr 24. Epub 2019 Apr 24.

Premature and uncomplete drug release are the typical bottlenecks of drug release in traditional chemotherapy. Synergistic therapies are high desirable in medicine and biology since they can compensate for the drawbacks of single therapy and significantly enhance the therapeutic efficacy. Herein, a novel NIR-activated polymeric nanoplatform with upper critical solution temperature (UCST) was constructed for image-guided synergistic photothermal and chemotherapy. Read More

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http://dx.doi.org/10.1021/acs.biomac.9b00321DOI Listing

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

Development and radiosynthesis of the first F-labeled inhibitor of monocarboxylate transporters (MCTs).

J Labelled Comp Radiopharm 2019 Apr 24. Epub 2019 Apr 24.

Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, Leipzig, Germany.

Monocarboxylate transporters 1 and 4 (MCT1 and MCT4) are involved in tumor development and progression. Their expression levels are related to clinical disease prognosis. Accordingly, both MCTs are promising drug targets for treatment of a variety of human cancers. Read More

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http://dx.doi.org/10.1002/jlcr.3739DOI Listing

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

National Cancer Institute (NCI) state of the science: Targeted radiosensitizers in colorectal cancer.

Cancer 2019 Apr 24. Epub 2019 Apr 24.

Clinical Radiation Oncology Branch, Radiation Research Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Colorectal cancer (CRC) represents a major public health problem as the second leading cause of cancer-related mortality in the United States. Of an estimated 140,000 newly diagnosed CRC cases in 2018, roughly one-third of these patients will have a primary tumor located in the distal large bowel or rectum. The current standard-of-care approach includes curative-intent surgery, often after preoperative (neoadjuvant) radiotherapy (RT), to increase rates of tumor down-staging, clinical and pathologic response, as well as improving surgical resection quality. Read More

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http://dx.doi.org/10.1002/cncr.32150DOI 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

Estimation of the Required Lipoprotein(a)-Lowering Therapeutic Effect Size for Reduction in Coronary Heart Disease Outcomes: A Mendelian Randomization Analysis.

JAMA Cardiol 2019 Apr 24. Epub 2019 Apr 24.

Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.

Importance: Genetic and epidemiologic data suggest that lipoprotein(a) (Lp[a]) is one of the strongest genetically determined risk factors for coronary heart disease (CHD). Specific therapies to lower Lp(a) are on the horizon, but the required reduction of Lp(a) to translate into clinically relevant lowering of CHD outcomes is a matter of debate.

Objective: To estimate the required Lp(a)-lowering effect size that may be associated with a reduction of CHD outcomes compared with the effect size of low-density lipoprotein cholesterol (LDL-C)-lowering therapies. Read More

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http://dx.doi.org/10.1001/jamacardio.2019.1041DOI 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

Mining novel biosynthetic machineries of secondary metabolites from actinobacteria.

Authors:
Yohei Katsuyama

Biosci Biotechnol Biochem 2019 Apr 24:1-10. Epub 2019 Apr 24.

a Department of Biotechnology, Graduate School of Agriculture and Life Sciences , The University of Tokyo , Bunkyo-ku , Japan.

Secondary metabolites produced by actinobacteria have diverse structures and important biological activities, making them a useful source of drug development. Diversity of the secondary metabolites indicates that the actinobacteria exploit various chemical reactions to construct a structural diversity. Thus, studying the biosynthetic machinery of these metabolites should result in discovery of various enzymes catalyzing interesting and useful reactions. Read More

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http://dx.doi.org/10.1080/09168451.2019.1606700DOI Listing

Lizard Tail Extracts Exert Protective Effect Against Oxidative Stress-Induced Cellular Senescence in Human Fibroblasts.

J Med Food 2019 Apr 24. Epub 2019 Apr 24.

1 Department of Biological Science, Dong-A University, Busan, Korea.

Lizards are the evolutionary closest animals to humans among the self-renewable species. Recent reports show that lizard tail extracts (LTE) inhibit the proliferation and angiogenesis of cancer cells but do not show any toxicity against human fibroblast cells. Nevertheless, few scientific studies investigated the effects of LTE on the treatment of skin diseases, especially oxidative stress aging. Read More

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http://dx.doi.org/10.1089/jmf.2018.4369DOI Listing

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

Genotoxicity Evaluation of the Soybean Isoflavone Genistein in Human Papillary Thyroid Cancer Cells. Study of Its Potential Use in Thyroid Cancer Therapy.

Nutr Cancer 2019 Apr 24:1-10. Epub 2019 Apr 24.

b Department of Clinical and Experimental Medicine - Section of Applied Biology and Genetics , University of Pisa , Pisa , Italy.

Genistein is one of the several known isoflavonic phytoestrogens found in a number of plants, with soybeans and soy products being the primary food source. The aim of the study is to evaluate if genistein is able to exert antineoplastic action in primary human papillary thyroid cancer (PTC) cells. Thyroid tissues were treated with genistein (1-10-50-100 µM). Read More

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http://dx.doi.org/10.1080/01635581.2019.1604004DOI Listing

Stiripentol for the treatment of seizures in Dravet syndrome.

Expert Rev Clin Pharmacol 2019 Apr 24:1-10. Epub 2019 Apr 24.

a University of Colorado Denver Anschutz School of Medicine , Children's Hospital Colorado , Aurora , CO , USA.

Introduction: Dravet syndrome is an early childhood-onset epilepsy syndrome characterized by drug-resistant seizures, frequent episodes of status epilepticus, and the development of neurocognitive impairment. Seizure freedom in this condition is rare and there is a higher rate of sudden unexplained death in epilepsy patients (SUDEP) than other epilepsy syndromes. Stiripentol is a recently approved medication with an indication specifically for the treatment of seizures in children with Dravet syndrome. Read More

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http://dx.doi.org/10.1080/17512433.2019.1605904DOI Listing

Anti-miRNA21 and resveratrol-loaded polysaccharide-based mesoporous silica nanoparticle for synergistic activity in gastric carcinoma.

J Drug Target 2019 Apr 24:1-31. Epub 2019 Apr 24.

b Department of Endoscopy Center , China-Japan Union Hospital of Jilin University , Changchun , Jilin , China , 130033.

Anti-miR21 and resveratrol (RSV)-loaded mesoporous silica nanoparticles conjugated with hyaluronic acid (HA) were developed to enhance therapeutic efficacy in gastric carcinoma. The surface conjugation of HA, which acts as a targeting ligand to the overexpressed CD44 receptor on gastric cancer cells, was clearly identified by the presence of a greyish shell on the dark mesoporous silica nanoparticles. Confocal laser-scanning microscopy and flow cytometry analysis showed higher cellular internalization of HA/RSVmirNP compared to RSVmirNP. Read More

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http://dx.doi.org/10.1080/1061186X.2019.1610766DOI 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

The Role of Surface Chemistry in Mediating the Uptake of Ultrasmall Iron Oxide Nanoparticles by Cancer Cells.

ACS Appl Mater Interfaces 2019 Apr 24. Epub 2019 Apr 24.

Ultrasmall iron oxide nanoparticles (USIONPs) (< 4 nm) have recently attracted significant attention because of their potential as positive T1 magnetic resonance imaging (MRI) contrast agent contrary to larger superparamagnetic iron oxide nanoparticles (> 6 nm) which act as negative T2 MRI contrast agent. However, studies on the cellular uptake behavior of these nanoparticles are very limited compared to their counterpart, larger sized superparamagnetic iron oxide nanoparticles. In particular, the effects of specific nanoparticle parameters on the cellular uptake behavior of USIONPs by various cancer cells are not available. Read More

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http://dx.doi.org/10.1021/acsami.9b00606DOI Listing

HSP90 inhibitor, NVP-AUY922, improves myelination in vitro and supports the maintenance of myelinated axons in neuropathic mice.

ACS Chem Neurosci 2019 Apr 24. Epub 2019 Apr 24.

Hereditary demyelinating neuropathies linked to peripheral myelin protein 22 (PMP22) involve the disruption of normal protein trafficking and are therefore relevant targets for chaperone therapy. Using a small molecule HSP90 inhibitor, EC137, in cell culture models, we previously validated the chaperone pathway as a viable target for therapy development. Here, we tested five commercially available inhibitors of HSP90 and identified, BIIB021 and AUY922, to support Schwann cell viability and enhance chaperone expression. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00105DOI Listing

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

Secondary prevention after stroke/transient ischemic attack, a randomized audit&feedback trial.

Acta Neurol Scand 2019 Apr 24. Epub 2019 Apr 24.

Karolinska Institutet Stroke Research Network at Södersjukhuset, Sweden.

Objectives: The clinical benefits of use of secondary preventive pharmacotherapy in ischemic stroke/TIA have been previously demonstrated. A potential target for facilitating use of recommended medication is primary care physicians. Therefore, we carried out an audit&feedback intervention aimed at primary care centers. Read More

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http://dx.doi.org/10.1111/ane.13109DOI Listing

[Epilepsy surgery for refractory neurocysticercosis-related epilepsy].

Rev Neurol 2019 May;68(9):384-388

Western University, London, Ontario, Canada.

Introduction: Neurocysticercosis is one of the most frequent causes of epilepsy worldwide, with some cases going into refractoriness. For that reason, surgical treatment should be considered, particularly lesionectomy, with or without temporal lobectomy.

Case Reports: From our series of patients with drug-resistant epilepsy from 2008 to 2018, we selected all cases with one or more lesions suggestive of neurocysticercosis who underwent epilepsy surgery. Read More

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http://dx.doi.org/10.33588/rn.6809.2018354DOI Listing

Cocaine relapse and health-related quality of life: a 23 weeks study.

Actas Esp Psiquiatr 2019 Mar 1;47(2):37-44. Epub 2019 Mar 1.

Sección de Adicciones y Patología Dual, Hospital Universitario Vall Hebron-Agencia de Salud Pública de Barcelona (ASPB). Barcelona (España) Servicio de Psiquiatría, Hospital Universitario Vall Hebron. Universidad Autónoma de Barcelona. CIBERSAM (Spain).

Introduction: Cocaine dependence is a disorder where relapses are frequently presented and many factors are involved. Furthermore, cocaine dependence is associated with poor health-related quality of life (HRQoL) outcomes. This study aims to explore perceived HRQoL as an indicator of drug relapse in cocaine-dependent patients (CDP). Read More

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