5,397,173 results match your criteria Drug Resistance Updates[Journal]

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Acknowledgement for Reviewers.

Authors:

Drug Res (Stuttg) 2018 Dec 11;68(12):665-668. Epub 2018 Dec 11.

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December 2018
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miR-494 Sensitizes Gastric Cancer Cells to TRAIL Treatment Through Downregulation of Survivin.

Cell Physiol Biochem 2018 7;51(5):2212-2223. Epub 2018 Dec 7.

Department of Internal Medicine, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou,

Background/aims: TNF-related apoptosis-inducing ligand (TRAIL) is a novel and low-toxic anti-tumor drug used for various cancers. However, cancer cells usually develop mechanisms to acquire the resistance against TRAIL. Among these changes, dysregulation of microRNAs (miRNAs) usually occurs in cancer cells and is responsible for induction of drug resistance. Read More

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December 2018

Stability and mean residence times for hybrid epithelial/mesenchymal phenotype.

Phys Biol 2018 Dec 11. Epub 2018 Dec 11.

Physics, Indian Institute of Science Education and Research (IISER) Kolkata, Kolkata, INDIA.

Cancer metastasis and drug resistance remain unsolved clinical challenges. A phenotypic transition that is often implicated in both these processes is Epithelial-Mesenchymal Transition (EMT) during which epithelial cells weaken their cell-cell adhesion and gain traits of migration and invasion, typical of mesenchymal cells. However, recent studies indicate that apart from these two states, cells can also exist in one or more hybrid E/M state(s) which plays an aggressive role in progression of the disease. Read More

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December 2018

Role and mechanisms of a three-dimensional bioprinted microtissue model in promoting proliferation and invasion of growth-hormone-secreting pituitary adenoma cells.

Biofabrication 2018 Dec 11. Epub 2018 Dec 11.

Department of Mechanical Engineering, Biomanufacturing Center, Tsinghua University, Beijing, CHINA.

Growth-hormone-secreting pituitary adenoma (GHSPA) is a benign tumour with a high incidence and large economic burden, which greatly affects quality of life. The aetiological factors are yet to be clarified for GHSPA. Conventional two-dimensional (2D) monolayer culture of tumour cells cannot ideally reflect the growth status of tumours in the physiological environment, and insufficiencies of in vitro models have severely restricted the progress of cancer research. Read More

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December 2018

Novel hepatoprotective role of Leonurine hydrochloride against experimental non-alcoholic steatohepatitis mediated via AMPK/SREBP1 signaling pathway.

Biomed Pharmacother 2018 Dec 7;110:571-581. Epub 2018 Dec 7.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, 210009, Nanjing, Jiangsu, China; Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, 210009, Nanjing, Jiangsu, China. Electronic address:

Background And Aims: Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome and is characterized by steatosis, inflammation, and fibrosis. We aim to characterize the hepatoprotective effects of Leonurine hydrochloride (LH) and the possible pathway in a cell and rodent model of diet-induced steatohepatitis (NASH).

Methods: For in vitro studies, Palmitic acid (PA) and free fatty acid (FFA) induced HepG2 and HL7702 steatosis cell models were used. Read More

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December 2018

The refractory epilepsy screening tool for Lennox-Gastaut syndrome (REST-LGS).

Epilepsy Behav 2018 Dec 8;90:148-153. Epub 2018 Dec 8.

Icahn School of Medicine at Mount Sinai Health Systems, 10 Union Square East, Suite 5G, New York, NY 10003, USA. Electronic address:

Background: The complex clinical presentation and progression of Lennox-Gastaut syndrome (LGS) can complicate the accurate diagnosis of this severe, lifelong, childhood-onset epilepsy, often resulting in suboptimal treatment. The Refractory Epilepsy Screening Tool for LGS (REST-LGS) was developed to improve the identification of patients with LGS.

Methods: Using the Modified Delphi Consensus, a group of experts developed and tested the REST-LGS Case Report Form (CRF) comprising 8 criteria (4 major, 4 minor) considered potentially indicative of LGS. Read More

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December 2018

Conformational and solution dynamics of hemoglobin (Hb) in presence of a cleavable gemini surfactant: Insights from spectroscopy, atomic force microscopy, molecular docking and density functional theory.

J Colloid Interface Sci 2018 Dec 3;538:489-498. Epub 2018 Dec 3.

Department of Chemistry, Arba Minch University, Ethiopia.

Herein, we have explored the conformational alterations of hemoglobin (Hb) in presence of a cleavable gemini surfactant (C16-C4O2-C16). The concerned surfactant was found to induce significant structural perturbations in Hb. UV-vis spectroscopy, steady-state/time-resolved fluorescence, and other utilized techniques have authenticated the complexation of Hb with the gemini surfactant. Read More

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December 2018

Molecular docking, molecular dynamics simulations and QSAR studies on some of 2-arylethenylquinoline derivatives for inhibition of Alzheimer's amyloid-beta aggregation: Insight into mechanism of interactions and parameters for design of new inhibitors.

J Mol Graph Model 2018 Dec 4;87:129-143. Epub 2018 Dec 4.

Chemistry Department, Faculty of Science, Shahid Bahonar University of Kerman, Kerman, Iran. Electronic address:

Alzheimer's disease is characterized using amyloid-beta (Aβ) aggregation. The present work was carried out to extend and design a novel quantitative structure-activity relationship (QSAR) model on inhibition efficiency of some of new 2-arylethenylquinoline derivatives against the Aβ peptide aggregation. The QSAR study, molecular docking and molecular dynamics (MD) simulations were performed to explore the influence of the structural features and investigate the molecular mechanism of ligands interactions with the Aβ peptide. Read More

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December 2018

Natural products: Potential therapeutic agents in multiple sclerosis.

Int Immunopharmacol 2018 Dec 8;67:87-97. Epub 2018 Dec 8.

Murad Research Center for Modernized Chinese Medicine, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Key Laboratory of Smart Drug Delivery, Fudan University, Ministry of Education, Shanghai 201203, China. Electronic address:

Multiple sclerosis is an autoimmune neurodegenerative disease, which usually caused by inflammation, demyelination, and axonal injury. The currently available medications for multiple sclerosis do not directly promote myelin sheath repair. Therefore, many researches have attempted to achieve better therapeutic effects through promoting remyelination. Read More

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December 2018

An LC-MS/MS method for quantification of abiraterone, its active metabolites D(4)-abiraterone (D4A) and 5α-abiraterone, and their inactive glucuronide derivatives.

J Chromatogr B Analyt Technol Biomed Life Sci 2018 Dec 4;1104:249-255. Epub 2018 Dec 4.

Pharmacogenomics Laboratory, Centre Hospitalier Universitaire (CHU) de Québec, - Université Laval Research Center and Faculty of Pharmacy, Laval University, Québec city, QC, Canada; Canada Research Chair in Pharmacogenomics, Canada. Electronic address:

Abiraterone acetate (AA) is a prodrug of abiraterone, a selective and potent steroidal cytochrome P450 17alpha- hydroxylase-17,20-lyase (CYP17A1) blocking androgen synthesis in the treatment of advanced prostate cancer. Abiraterone (Abi) is metabolized to D(4)-abiraterone (D4A) directly blocking CYP17A1 and other steroidogenic enzymes and antagonizing the androgen receptor (AR). D4A is converted by 5α-reductase to 3-keto-5α-abiraterone (5α-Abi), an AR agonist. Read More

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December 2018

A novel MUC1 aptamer-modified PLGA-epirubicin-PβAE-antimir-21 nanocomplex platform for targeted co-delivery of anticancer agents in vitro and in vivo.

Colloids Surf B Biointerfaces 2018 Dec 4;175:231-238. Epub 2018 Dec 4.

Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Conventional chemotherapy suffers from several drawbacks, including toxic side effects together with the development of resistance to the chemical agents. Therefore, exploring alternative therapeutic approaches as well as developing targeted delivery systems are in demand. Oligonucleotide-based therapy has emerged as a promising and alternative procedure for treating malignancies involving gene-related diseases. Read More

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December 2018

Synthesizing, characterizing, and toxicity evaluating of Phycocyanin-ZnO nanorod composites: A back to nature approaches.

Colloids Surf B Biointerfaces 2018 Dec 4;175:221-230. Epub 2018 Dec 4.

Division of Industrial & Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), P.O. Box 14155-6343, Tehran, Iran. Electronic address:

C-Phycocyanin pigment was purified from a native cyanobacterial strain using a novel consecutive multi-step procedure and utilized for the first time for the green synthesis of phycocyanin-zinc oxide nanorods (PHY-ZnO NRs) by a simple, low-cost and eco-friendly approach. The PHY-ZnO NRs were characterized using UV-vis spectroscopy, X-ray diffraction (XRD), zeta potential measurement, FTIR, SEM, TEM, differential scanning calorimetry (DSC), thermogravimetric (TGA), and EDX spectroscopy analysis. The UV-vis spectra showed an absorption band at 364 nm which is characteristic of ZnO nanoparticles (ZnONPs). Read More

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December 2018

Allicin enhances antimicrobial activity of macrophages during Mycobacterium tuberculosis infection.

J Ethnopharmacol 2018 Dec 8. Epub 2018 Dec 8.

Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India. Electronic address:

Ethnopharmacological Relevance: The emergence of drug-resistant Mycobacterium tuberculosis (M.tb) strains has severely hampered global efforts towards tuberculosis (TB) eradication. The internationally accepted therapy "Directly Observed Treatment Short-course (DOTS)" is lengthy, and incorporates risks for the generation of drug-resistant M. Read More

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December 2018
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Significant effect of infection and food intake on sirolimus pharmacokinetics and exposure in pediatric patients with acute lymphoblastic leukemia.

Eur J Pharm Sci 2018 Dec 8. Epub 2018 Dec 8.

Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH, USA. Electronic address:

Background: Sirolimus is increasingly investigated as a new targeted therapy in pediatric populations. To date, population pharmacokinetic (PK) studies have identified several factors that explain in part the large between-patient variability in sirolimus PK. However, within-patient variability in sirolimus PK is not well documented. Read More

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December 2018

Sex differences in the temporal neuromolecular and synaptogenic effects of the rapid-acting antidepressant drug ketamine in the mouse brain.

Neuroscience 2018 Dec 8. Epub 2018 Dec 8.

Department of Biology & Center for Tissue Regeneration and Engineering at Dayton (TREND), University of Dayton, Dayton, Ohio, USA. Electronic address:

Preclinical evidence suggests that ketamine's rapid and sustained antidepressant actions are due to the induction of synaptogenesis in the medial prefrontal cortex (mPFC) and the hippocampus (HIPP), two brain regions implicated in the pathophysiology of major depression. However, research on the neurobiological effects of ketamine has focused almost exclusively on males. Findings from our group and others indicate that female rodents are more reactive to ketamine's antidepressant effects, since they respond to lower doses in antidepressant-predictive behavioral models. Read More

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December 2018

Resistance to Epigenetic-Targeted Therapy Engenders Tumor Cell Vulnerabilities Associated with Enhancer Remodeling.

Cancer Cell 2018 Dec;34(6):922-938.e7

Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address:

Drug resistance represents a major challenge to achieving durable responses to cancer therapeutics. Resistance mechanisms to epigenetically targeted drugs remain largely unexplored. We used bromodomain and extra-terminal domain (BET) inhibition in neuroblastoma as a prototype to model resistance to chromatin modulatory therapeutics. Read More

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December 2018

Lymphocyte-Specific Chromatin Accessibility Pre-determines Glucocorticoid Resistance in Acute Lymphoblastic Leukemia.

Cancer Cell 2018 Dec;34(6):906-921.e8

Children's Cancer Institute, Lowy Cancer Research Centre, UNSW, Sydney, NSW 2052, Australia. Electronic address:

Glucocorticoids play a critical role in the treatment of lymphoid malignancies. While glucocorticoid efficacy can be largely attributed to lymphocyte-specific apoptosis, its molecular basis remains elusive. Here, we studied genome-wide lymphocyte-specific open chromatin domains (LSOs), and integrated LSOs with glucocorticoid-induced RNA transcription and chromatin modulation using an in vivo patient-derived xenograft model of acute lymphoblastic leukemia (ALL). Read More

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December 2018

Loss of the FAT1 Tumor Suppressor Promotes Resistance to CDK4/6 Inhibitors via the Hippo Pathway.

Cancer Cell 2018 Dec;34(6):893-905.e8

Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA; Breast Medicine Service, Department of Medicine, MSKCC, New York, NY 10065, USA; Weill-Cornell Medical College, New York, NY 10065, USA. Electronic address:

Cyclin dependent kinase 4/6 (CDK4/6) inhibitors (CDK4/6i) are effective in breast cancer; however, drug resistance is frequently encountered and poorly understood. We conducted a genomic analysis of 348 estrogen receptor-positive (ER) breast cancers treated with CDK4/6i and identified loss-of-function mutations affecting FAT1 and RB1 linked to drug resistance. FAT1 loss led to marked elevations in CDK6, the suppression of which restored sensitivity to CDK4/6i. Read More

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December 2018
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BH3-Mimetic Drugs: Blazing the Trail for New Cancer Medicines.

Cancer Cell 2018 Dec;34(6):879-891

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia. Electronic address:

Defects in apoptotic cell death can promote cancer and impair responses of malignant cells to anti-cancer therapy. Pro-survival BCL-2 proteins prevent apoptosis by keeping the cell death effectors, BAX and BAK, in check. The BH3-only proteins initiate apoptosis by neutralizing the pro-survival BCL-2 proteins. Read More

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December 2018

Further Evidence Regarding the Important Role of Chlorine Atoms of Aripiprazole on Binding to the Site II Area of Human Albumin.

J Pharm Sci 2018 Dec 8. Epub 2018 Dec 8.

Faculty of Pharmaceutical Sciences, Sojo University; DDS Research Institute, Ikeda 4-22-Nishi-ku, Kumamoto 860-0082, Japan. Electronic address:

Previously, we reported on the high affinity binding of aripiprazole (ARP), an antipsychotic drug, to human albumin and the role of the chlorine atom of ARP on this binding. In this study, we investigated the binding mode of ARP to human albumin in detail using ARP derivatives and several animal-derived albumins. ARP bound strongly to human and dog albumin. Read More

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December 2018

A new human pyridinium metabolite of furosemide, inhibitor of mitochondrial complex I, is a candidate inducer of neurodegeneration.

Biochem Pharmacol 2018 Dec 8. Epub 2018 Dec 8.

Université Paris-Est, Laboratoire CRRET ERL-CNRS 9215, UPEC, F-94010, Créteil, France. Electronic address:

Pharmaceuticals and their by-products are increasingly a matter of concern, because of their unknown impacts on human health and ecosystems. The lack of information on these transformation products, which toxicity may exceed that of their parent molecules, makes their detection and toxicological evaluation impossible. Recently we characterized the Pyridinium of furosemide (PoF), a new transformation product of furosemide, the most widely used diuretic and an emerging pollutant. Read More

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December 2018

Literature review of apheresis procedures performed perioperatively in cardiac surgery for ASFA category indications.

J Clin Apher 2018 Dec 8. Epub 2018 Dec 8.

Department of Clinical Hematology - Blood Bank and Hemostasis, Onassis Cardiac Surgery Center, Kallithea, Greece.

Background: Perioperative therapeutic plasma exchange in patients with cardiovascular diseases poses several challenges, including alterations in intravascular volume, serum electrolytes, the coagulation cascade, and drug pharmacokinetics.

Methods: This review article summarizes different indications of plasma exchange for patients requiring cardiac surgery based on reported case reports and case series.

Results: The most common reported indication is plasma exchange for the management of allosensitized cardiac transplant candidate patients in combination with immunosuppressive regimens, which increases the likelihood of obtaining a cross-match-negative allograft, improving post-transplant clinical outcome. Read More

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December 2018

Ciprofloxacin resistance among Campylobacter jejuni isolates obtained from shelter dogs in Texas.

Zoonoses Public Health 2018 Dec 9. Epub 2018 Dec 9.

Texas A&M University, College Station, Texas.

There are few epidemiologic studies on the shedding of Campylobacter among dogs in the United States, despite the potential public health implications. Our objectives were to estimate the prevalence of faecal Campylobacter shedding among Texas shelter dogs as detected by culture methods and to characterize the isolates by species and antimicrobial susceptibility. Using a cross-sectional study design, faecal samples were collected from 185 dogs in six animal shelters throughout Texas between May and December 2014. Read More

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December 2018
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Major bleeding with antithrombotic agents: a 2012-2015 study using the French nationwide Health Insurance Database (SNIIRAM) linked to emergency departments records within five areas. Rationale and design of SACHA study.

Fundam Clin Pharmacol 2018 Dec 10. Epub 2018 Dec 10.

CHU de Brest, F-29200, France.

Bleeding represents the most recognised and feared complications of antithrombotic drugs including oral anticoagulants. Previous studies showed inconsistent results on the safety profile. Among explanations, bleeding definition could vary and classification bias exist related to the lack of medical evaluation. Read More

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December 2018

Management of common femoral artery occlusive disease: A review of endovascular treatment strategies and outcomes.

Catheter Cardiovasc Interv 2018 Dec 7. Epub 2018 Dec 7.

Department of Cardiovascular Medicine, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts.

Isolated atherosclerotic lesions of the common femoral artery (CFA) are rare but can produce significant claudication and critical limb ischemia. To date, the "gold standard" treatment for this entity has been common femoral endarterectomy (CFE) with or without patch angioplasty. However, surgery does have significant early postoperative complications, with a 15% combined mortality/morbidity. Read More

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December 2018
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Treating tumors at low drug doses using an aptamer-peptide synergistic drug conjugate.

Angew Chem Int Ed Engl 2018 Dec 11. Epub 2018 Dec 11.

Harvard University John A Paulson School of Engineering and Applied Sciences, 29 Oxford Street, 02138, Cambridge, UNITED STATES.

Combination chemotherapy must strike a difficult balance between safety and efficacy. Current regimens suffer from poor therapeutic impact because drugs are given at their maximum tolerated dose (MTD), which compounds the toxicity risk and exposes tumors to non-optimal drug ratios. We developed a modular framework that selectively delivers drug combinations at synergistic ratios via tumor-targeting aptamers for effective low-dose treatment. Read More

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December 2018

An in vitro assessment for evaluating the efficiency of β-d-mannuronic acid (M2000) in myelodysplastic syndrome.

J Cell Physiol 2018 Dec 10. Epub 2018 Dec 10.

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

β-d-Mannuronic acid (M2000), a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive properties, has been previously shown to exhibit potential therapeutic effects on autoimmune diseases. Immunosuppression therapy has been a standard approach for myelodysplastic syndrome (MDS) for many years. We evaluated the effect of M2000 on isolated peripheral blood mononuclear cells (PBMCs) from patients with MDS. Read More

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December 2018

Whole-genome sequencing for combatting antibiotic resistance.

Authors:
David Gurwitz

Drug Dev Res 2018 Dec 10. Epub 2018 Dec 10.

Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

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December 2018

Spectrofluorimetric determination of eptifibatide in human plasma and dosage form.

Luminescence 2018 Dec 11. Epub 2018 Dec 11.

Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El- Aini Street, Cairo, Egypt.

A spectrofluorimetric method for the determination of eptifibatide is presented based on its native fluorescence. The type of solvent and the wavelength of maximum excitation and emission were carefully selected to optimize the experimental conditions. Under the specified experimental conditions, the linearities obtained between the emission intensity and the corresponding concentrations of eptifibatide were in the range 0. Read More

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December 2018
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A New Drug Delivery System based on Tauroursodeoxycholic Acid and PEDOT.

Chemistry 2018 Dec 11. Epub 2018 Dec 11.

ITALY.

Localized drug delivery represents one of the most challenging uses of systems based on conductive polymer films. Typically, anionic drugs are incorporated within conductive polymers through the electrostatic interaction with the positively charged polymer. Following this approach, the synthetic glucocorticoid Dexamethasone-phosphate is often delivered from neural probes to reduce the inflammation of the surrounding tissue. Read More

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December 2018

How Representative are the Patients Included in the CV outcome Trials with SGLT2 Inhibitors of a General Type 2 Diabetes Population? A Large European Observational study.

Diabetes Obes Metab 2018 Dec 9. Epub 2018 Dec 9.

University Medical Center Groningen and Bethesda Diabetes Research Center, The Netherlands.

Aims: Enrollment criteria vary substantially between the cardiovascular outcome trials (CVOTs) of sodium-glucose cotransporter-2 inhibitors (SGLT-2is), impacting how representative a trial population is to the general type 2 diabetes (T2D) population. The aim was to evaluate the representativeness of four SGLT-2i CVOTs to a general T2D population.

Methods: T2D patients were included from Germany, the Netherlands, Norway, and Sweden. Read More

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December 2018

Early outcome of magnesium bioresorbable scaffold implantation in acute coronary syndrome-the initial report from the Magmaris-ACS registry.

Catheter Cardiovasc Interv 2018 Dec 10. Epub 2018 Dec 10.

Department of Cardiology, Poznan University of Medical Sciences, Poland.

Objectives: The Magmaris-ACS Registry is the first assessment of the Magmaris implantation in the acute coronary syndrome (ACS) population.

Background: Bioresorbable vascular scaffolds (BRS), the newest coronary stent technology, was developed to overcome the limitations of the metallic drug-eluting stents (DES). Current promising data of the Magmaris in patients with stable angina have encouraged to validate the second generation BRS in ACS indications. Read More

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December 2018

Medication dosing for heart failure with reduced ejection fraction - opportunities and challenges.

Eur J Heart Fail 2018 Dec 10. Epub 2018 Dec 10.

Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.

Multiple drug classes have shown incremental benefits in heart failure with reduced ejection fraction. Most of these trials were designed to achieve specific doses of the investigational agent. Clinical practice guidelines recommend using the same target dosing of therapies, as tolerated. Read More

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December 2018

Case of purpuric drug eruption probably induced by panitumumab.

J Dermatol 2018 Dec 7. Epub 2018 Dec 7.

Department of Dermatology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.

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December 2018

microRNAs in cancer stem cells: Biology, pathways, and therapeutic opportunities.

J Cell Physiol 2018 Dec 7. Epub 2018 Dec 7.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Cancer stem cells (CSCs) are a small subpopulation of tumor cells that have been identified in most types of cancer. Features that distinguish them from the bulk of tumor cells include their pluripotency, self-renewal capacity, low proliferation rate, and tumor-initiating ability. CSCs are highly malignant, as they confer drug resistance and facilitate tumor progression, relapse, and metastasis. Read More

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December 2018
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A high-throughput glutathione trapping assay with combined high sensitivity and specificity in high resolution mass spectrometry by applying product ion extraction and data-dependent neutral loss.

J Mass Spectrom 2018 Dec 10. Epub 2018 Dec 10.

Department of Drug Metabolism and Pharmacokinetics, Sanofi, 153 2nd Avenue, Waltham, MA, 02451, USA.

Reactive metabolites are thought to play a pivotal role in the pathogenesis of some drug induced liver injury (DILI) and idiosyncratic adverse drug reactions (IADRs), which is of concern to patient safety and has been a cause of drugs being withdrawn from the market place. To identify drugs with a lower propensity for causing DILI and /or IADRs, high-throughput assays to capture reactive metabolites are required in pharmaceutical industry for early drug discovery risk assessment. We describe the development of an assay to detect glutathione adducts with combined high sensitivity, enhanced specificity and rapid data analysis. Read More

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December 2018

Neuroactive steroid levels and cocaine use chronicity in men and women with cocaine use disorder receiving progesterone or placebo.

Am J Addict 2018 Dec 11. Epub 2018 Dec 11.

The Yale Stress Center, Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.

Background And Objectives: Neuroactive steroids (NAS) may play a role in addiction, with observed increases in response to acute stress and drug use, but decreases with chronic substance use, suggesting that NAS neuroadaptations may occur with chronic substance use. However, levels of NAS in addicted individuals have not been systematically examined. Here, we evaluated a panel of NAS in men and women with cocaine use disorder (CUD) who participated in a clinical laboratory study of progesterone. Read More

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December 2018

Differential regulation of intestinal and hepatic CYP3A by 1α,25-dihydroxyvitamin D : Effects on in vivo oral absorption and disposition of buspirone in rats.

Drug Dev Res 2018 Dec 10. Epub 2018 Dec 10.

Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan, South Korea.

1α,25-Dihydroxyvitamin D (also called 1,25(OH) D or calcitriol) is the biologically active form of vitamin D, which functions as a ligand to the vitamin D receptor (VDR). It was previously reported that intestinal cytochrome P450 3A (CYP3A) expression was altered by 1,25(OH) D -mediated VDR activation. However, to clarify whether the change in CYP3A subfamily expression by VDR activation can affect metabolic function, further evidence is needed to prove the effect of 1,25(OH) D treatment on CYP3A-mediated drug metabolism and pharmacokinetics. Read More

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December 2018
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Propensity-score-based priors for Bayesian augmented control design.

Pharm Stat 2018 Dec 9. Epub 2018 Dec 9.

Division of Biostatistics, Center for Devices and Radiological Health, Food, and Drug Administration, Silver Spring, Maryland, USA.

Drug developers are required to demonstrate substantial evidence of effectiveness through the conduct of adequate and well-controlled (A&WC) studies to obtain marketing approval of their medicine. What constitutes A&WC is interpreted as the conduct of randomized controlled trials (RCTs). However, these trials are sometimes unfeasible because of their size, duration, and cost. Read More

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December 2018
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What role does pyroptosis play in microbial infection?

J Cell Physiol 2018 Dec 7. Epub 2018 Dec 7.

College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, China.

Pyroptosis, a type of programmed cell death mediated by gasdermin, is characterized by the swelling and rupture of cells, release of cellular contents and a strong inflammatory response, which is critical for controlling microbial infection. Pattern recognition receptors recognize the intracellular and extracellular pathogenic microbial components and stimulate the organism's inflammatory response by activating the pyroptosis signaling pathway and releasing interleukin-1β (IL-1β), IL-18, and other inflammatory factors to promote pathogen clearance and prevent infection. In the process of continuous evolution, pathogens have developed multiple strategies to modulate the occurrence of pyroptosis and thus enhance their ability to induce disease; that is, the competition between host cells and pathogens controls the occurrence of pyroptosis. Read More

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December 2018

Transforming Weakness into Strength: Photothermal-Therapy-Induced Inflammation Enhanced Cytopharmaceutical Chemotherapy as a Combination Anticancer Treatment.

Adv Mater 2018 Dec 9:e1805936. Epub 2018 Dec 9.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing, 210009, China.

A new synergistic treatment that combines photothermal therapy (PTT) and inflammation-mediated active targeting (IMAT) chemotherapy based on cytopharmaceuticals is developed. During PTT, the photothermal tumor ablation is accompanied by an inflammatory effect and upregulation of inflammatory factors at the tumor site, which may accelerate tumor regeneration. Moreover, PTT-induced inflammation can also recruit neutrophils (NEs) to the tumor site. Read More

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December 2018

Regulation of melanocyte stem cells in the pigmentation of skin and its appendages: Biological patterning and therapeutic potentials.

Exp Dermatol 2018 Dec 11. Epub 2018 Dec 11.

Integrative Stem Cell Center, China Medical University Hospital, China Medical University, Taichung, 40402, Taiwan.

Skin evolves essential appendages and indispensable types of cells that synergistically insulate the body from environmental insults. Residing in the specific regions in the skin such as epidermis, dermis and hair follicle, melanocytes perform an array of vital functions including defending the ultraviolet radiation and diversifying animal appearance. As one of the adult stem cells, melanocyte stem cells in the hair follicle bulge niche can proliferate, differentiate, and keep quiescence to control and coordinate tissue homeostasis, repair, and regeneration. Read More

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December 2018
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Efficient Cholera Toxin B Subunit-Based Nanoparticles with MRI Capability for Drug Delivery to the Brain Following Intranasal Administration.

Macromol Biosci 2018 Dec 7:e1800340. Epub 2018 Dec 7.

State Key Laboratory of Chemical Resource Engineering, Key Laboratory of Carbon Fiber and Functional Polymers (Ministry of Education), Beijing Laboratory of Biomedical Materials, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, China.

Alzheimer's disease (AD) is an incurable neurodegenerative brain disorder that exhibits clear pathologic changes in the hippocampus. Traditional drug delivery systems are ineffective due to the existence of the blood-brain barrier (BBB). In this study, an efficient, stable, and easily constructed nanosystem (CB-Gd-Cy5. Read More

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December 2018

Food Effect Study Design With Oral Drugs: Lessons Learned From Recently Approved Drugs in Oncology.

J Clin Pharmacol 2018 Dec 10. Epub 2018 Dec 10.

Quantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Waltham, MA, USA.

Evaluation of the effect of food on the pharmacokinetics of oral oncology drugs is critical to drug development, as food can mitigate or exacerbate toxicities and alter systemic exposure. Our aim is to expand on current US Food and Drug Administration (FDA) guidance and provide data-driven food-effect study design recommendations specific to the oncology therapeutic area. Data for recently approved small-molecule oncology drugs was extracted from the clinical pharmacology review in the sponsor's FDA submission package. Read More

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December 2018
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Angioplasty versus stenting for infrapopliteal arterial lesions in chronic limb-threatening ischaemia.

Cochrane Database Syst Rev 2018 Dec 8;12:CD009195. Epub 2018 Dec 8.

Department of Medical Imaging, Gold Coast University Hospital, 1 Hospital Blvd, Southport, Queensland, Australia, 4215.

Background: Chronic limb-threatening ischaemia (CLTI) is a manifestation of peripheral arterial disease (PAD) that includes chronic ischaemic rest pain or ischaemic skin lesions, ulcers, or gangrene for longer than two weeks. The severity of the disease depends on the extent of arterial stenosis and the availability of collateral circulation. Treatment for CLTI aims to relieve ischaemic pain, heal ischaemic ulcers, prevent limb loss, improve quality of life, and prolong survival. Read More

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December 2018
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Thermo-sensitive nanogel-laden bicontinuous microemulsion drug-eluting contact lenses.

J Biomed Mater Res B Appl Biomater 2018 Dec 7. Epub 2018 Dec 7.

Department of Biomedical Engineering, School of Medicine, Catholic University of Daegu, Daegu, 42472, South Korea.

The bicontinuous microemulsion contact lens (BMCL) has nanoporous biphasic structures (100-250 nm) that are interconnected via multiple nano-channels, providing suitable retention of various drugs for glaucoma. Timolol maleate (TM)-carried thermosensitive poly(N-isopropylacrylamide) (PNIPAM) nanogel (30-50 nm) was incorporated into BMCLs by soaking or by centrifuging plus soaking. Here, we present drug-loading and release in silicon- or polyethylene oxide-microemulsion BMCLs under various conditions. Read More

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December 2018
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