1,418,927 results match your criteria Drugs: Education Prevention and Policy [Journal]


Scalp nerves block for surgical clipping of cerebral aneurysms in patients allergic to nonsteroidal anti-inflammatory drugs.

J Clin Anesth 2018 Dec 12;54:156. Epub 2018 Dec 12.

Department of Anesthesiology, Showa University Hospital, Tokyo, Japan.

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December 2018

Detection of norovirus epidemic genotypes in raw sewage using next generation sequencing.

Environ Int 2018 Dec 12;123:282-291. Epub 2018 Dec 12.

Laboratory of Comparative and Environmental Virology, Oswaldo Cruz Institute, Rio de Janeiro, RJ, Brazil.

Noroviruses are a leading cause of epidemic and pandemic acute gastroenteritis (AGE) worldwide, and contaminated food and water are important routes for its transmission. Raw sewage has been used for viral surveillance to monitor the emergence of new norovirus strains with the potential to cause epidemics. In this study, we investigated norovirus occurrence and norovirus RNA levels in 156 samples collected from May 2013 to May 2014, across three different stages (52 samples each) of a wastewater treatment plant (WWTP) in Rio de Janeiro, Brazil. Read More

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December 2018

Checkpoint-modulating immunotherapies in tumor treatment: Targets, drugs, and mechanisms.

Int Immunopharmacol 2018 Dec 12;67:160-175. Epub 2018 Dec 12.

Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China; Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:

Tumor immunotherapy, as a new treatment of cancer, has been developing on the basis of tumor immunology. Tumor immunotherapy stimulates and enhances the function of immune system in human bodies, in order to control and kill tumor cells. It is often used as an adjuvant therapy combined with surgery, chemotherapy, radiotherapy and other conventional methods. Read More

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December 2018

An update on Drug Repurposing: Re-written saga of the drug's fate.

Biomed Pharmacother 2018 Dec 12;110:700-716. Epub 2018 Dec 12.

Pharamacological Modelling and Simulation Centre, M.S.Ramaiah University of Applied Sciences, Bangalore, Karnataka, India; Department of Pharmacy Practice, Faculty of Pharmacy, M.S.Ramaiah University of Applied Sciences, Bangalore, Karnataka, India.

Drug repurposing is an unconventional drug discovery approach to explore new therapeutic benefits of existing, shelved and the drugs in clinical trials. This approach is currently emerging to overcome the bottleneck constraints faced during traditional drug discovery in grounds of financial support, timeline and resources. In this direction, several efforts were made for the construction of stratagems based on bioinformatics and computational tools to intensify the repurposing process off-late. Read More

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December 2018

Epidemiology of Antibiotic Resistance in Lebanese Extra-Hospital Settings: an overview.

J Glob Antimicrob Resist 2018 Dec 12. Epub 2018 Dec 12.

Laboratoire Microbiologie Santé et Environnement (LMSE), Ecole Doctorale des Sciences et de Technologie, Faculté de Santé Publique, Université Libanaise, Tripoli, Lebanon. Electronic address:

Antibiotics can truly be considered the symbol of the 20th century's miracle drugs. However, excessive and inappropriate use of antibiotics in human and veterinary medicine has led to repercussions in terms of mortality, morbidity, and financial and societal costs, especially with the lack of novel drugs to combat infections caused by resistant pathogens. Unfortunately, antimicrobial resistance (AMR) has increased significantly worldwide in the past decades, particularly in developing third-world countries. Read More

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December 2018

A convenient strategy to overcome interference in LC-MS/MS analysis: Application in a microdose absolute bioavailability study.

J Pharm Biomed Anal 2018 Dec 10;165:198-206. Epub 2018 Dec 10.

Bioanalytical Sciences, Bristol-Myers Squibb, Princeton, NJ, 08543, USA.

Stable isotope labeled (SIL) compounds have been commonly used as internal standards (IS) to ensure the accuracy and quality of liquid chromatography-mass spectrometry (LC-MS) bioanalytical assays. Recently, the application of SIL drugs and LC-MS assays to microdose absolute bioavailability (BA) studies has gained increasing attention. This approach can provide significant cost and time saving, and higher data quality compared to the accelerator mass spectrometry (AMS)-based method, since it avoids the use of radioactive drug, high-cost AMS instrumentation and complex measurement processes. Read More

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December 2018
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Recent advances in bio-affinity chromatography for screening bioactive compounds from natural products.

J Pharm Biomed Anal 2018 Dec 7;165:182-197. Epub 2018 Dec 7.

Institute of Pharmaceutical Analysis, College of Pharmacy, Jinan University, Guangzhou, 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, 510632, China. Electronic address:

Natural products are one of the most important sources of leading compounds in drug discovery. Until now, rapid screening and identification of biologically active components from natural products remain a technical challenge. Bio-affinity chromatography (BAC) based approaches hold great promise in screening potential bioactive ligands from complex samples. Read More

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December 2018

An enzyme-based electrochemical biosensor probe with sensitivity to detect astrocytic versus glioma uptake of glutamate in real time in vitro.

Biosens Bioelectron 2018 Nov 16;126:751-757. Epub 2018 Nov 16.

Biomedical Engineering, PO Box 10157, Ruston, LA 71272, USA; Center for Biomedical Engineering and Rehabilitation Sciences, Louisiana Tech University, PO Box 10157, Ruston, LA 71272, USA. Electronic address:

Glutamate, a major excitatory neurotransmitter in the central nervous system, is essential for regulation of thought, movement, memory, and other higher functions controlled by the brain. Dysregulation of glutamate signaling is associated with severe neuropathological conditions, such as epilepsy, and glioma, a form of brain cancer. Glutamate signals are currently detected by several types of neurochemical probes ranging from microdialysis-based to enzyme-based carbon fiber microsensors. Read More

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November 2018
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Molecular structure and impact of amorphization strategies on intrinsic dissolution of spray dried indomethacin.

Eur J Pharm Sci 2018 Dec 12. Epub 2018 Dec 12.

Department of Pharmacy, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. Electronic address:

Amorphous systems prepared with different strategies, such as solid dispersion with colloidal particles or soluble polymers and inclusion complex, have been used for improving solubility and dissolution of poorly water soluble drugs. The purpose of this study was to obtain a deeper understanding of the impact of three different amorphous systems prepared by spray drying with silica, polyvinylpyrrolidone (PVP) or 2-hydroxypropyl-β-cyclodextrin (HPβCD) using indomethacin (IND) as a model drug. IND was spray dried with silica, PVP or HPβCD at different mass ratios, and the obtained powders were characterized with respect to colloidal silica particle redispersion, morphology, thermal properties, solid state properties and physical stability. Read More

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December 2018

Enhancement of the apparent solubility and bioavailability of Tadalafil nanoparticles via antisolvent precipitation.

Eur J Pharm Sci 2018 Dec 12. Epub 2018 Dec 12.

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China. Electronic address:

The ability to increase the bioavailability and dissolution of poorly soluble hydrophobic drugs has been a major challenge for pharmaceutical development. This study shows that the dissolution rate, apparent solubility and oral bioavailability of tadalafil (Td) can be improved by nano-sized amorphous particles prepared by using antisolvent precipitation. Acetone and an acetone-water solution (v:v, 9:1) were selected as solvents, with deionized water as the antisolvent. Read More

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December 2018
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Revival of a Potent Therapeutic Maytansinoid Agent using a Strategy that Combines Covalent Drug Conjugation with Sequential Nanoparticle Assembly.

Int J Pharm 2018 Dec 12. Epub 2018 Dec 12.

The First Affiliated Hospital, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, School of Medicine, Zhejiang University, Hangzhou, 310003, PR China. Electronic address:

Maytansine and its related analogues are a class of highly potent anti-proliferation agents that have failed to be exploited as clinical drugs for human therapy due to unacceptable systemic toxicity. Here, we delineate a novel strategy that combines rational drug conjugation with subsequent nanoparticle assembly to systemically deliver this highly potent and toxic drug. To demonstrate this concept, we covalently coupled the thiolated maytansine derivative, the DM1 agent, to amphiphilic block co-polymers, polyethylene glycol (PEG)-block-polylactide (PLA), in varying molecular weights to generate two prodrug constructs (i. Read More

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December 2018

Automated small-scale in vitro transfer model as screening tool for the prediction of in vivo-dissolution and precipitation of poorly solubles.

Int J Pharm 2018 Dec 12. Epub 2018 Dec 12.

Institute of Pharmacy, Department of Biopharmaceutics and Pharmaceutical Technology, University of Greifswald, Felix-Hausdorff-Strasse 3, 17489 Greifswald, Germany. Electronic address:

Precipitation testing, especially for weakly basic APIs, represents a key parameter in drug substance characterization during early development stages, where the amount of API available is limited. Therefore, it was the aim of this study to develop an automated small-scale in vitro transfer model to characterize the supersaturation and precipitation behavior of two poorly water-soluble drugs. Following automation and scale-down of the standard transfer model, the developed small-scale model was used to assess the impact of gastrointestinal variability, i. Read More

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December 2018

Gelatinized core liposomes: A new Trojan horse for the development of a novel timolol maleate glaucoma medication.

Int J Pharm 2018 Dec 12. Epub 2018 Dec 12.

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , Ain Shams University, African Union Street Authority Street, Abbassia, 11566 Cairo, Egypt.

Glaucoma treatment with ocular medications requires overcoming the corneal barrier to drug penetration. Liposomes have a great corneal penetration ability and affinity while suffering from poor stability and low entrapment of hydrophilic drugs accompanied by rapid drug release. This work aims to develop a new, effective and stable glaucoma medication with sustained drug release properties; Timolol maleate gelatinized core liposomes. Read More

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December 2018

Effects of cellular differentiation in human primary bronchial epithelial cells: Metabolism of 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone.

Toxicol In Vitro 2018 Dec 12. Epub 2018 Dec 12.

Division of Genetic and Molecular Toxicology, Division of Biochemical Toxicology, National Center for Toxicological Research, U.S Food and Drug Administration, Jefferson, AR 72079, United States. Electronic address:

Many of the toxicants in tobacco smoke undergo biotransformation in the lungs of smokers, both to reactive and to detoxified derivatives. Human air-liquid-interface (ALI) airway tissue models have emerged as an advanced in vitro model for evaluating the toxicity of inhaled substances; however, the metabolic potential of these cultures has not been evaluated extensively. In this study, we compared the metabolic activities of an ALI tissue model to the undifferentiated normal human primary bronchial epithelial (NHBE) cells from which it was derived. Read More

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December 2018
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FH535 inhibits proliferation and migration of colorectal cancer cells by regulating CyclinA2 and Claudin1 gene expression.

Gene 2018 Dec 12. Epub 2018 Dec 12.

Wenzhou Medical University School of Laboratory Medicine and Life Sciences, Wenzhou 325000, China. Electronic address:

Wnt signaling pathway plays a major role in the progression of colorectal cancer (CRC). Small molecules which can cut off this signal transduction can be promising anti-cancer drugs for CRC therapy. Therefore, we aimed to investigate the mechanisms of FH535, an inhibitor of the Wnt signaling pathway, on inhibiting proliferation and migration of colorectal cancer cells DLD-1 and SW620. Read More

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December 2018
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Protocol for evaluation of topical ophthalmic drug products in different compartments of fresh eye tissues in a rabbit model.

J Pharmacol Toxicol Methods 2018 Dec 12. Epub 2018 Dec 12.

Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, U.S. Food and Drug Administration, Center for Drug Evaluation and Research, White Oak Federal Research Center, 10903 New Hampshire Ave, Silver Spring, MD 20993, USA. Electronic address:

Topical ophthalmic drugs are the most commonly used dosage form to treat diseases of the anterior segment of the eye. Although this dosage form has the advantages of ease of application, small volume dose, and rapid action and is largely devoid of systemic adverse effects, the bioavailability is low due to pre-corneal anatomical barriers and the nature of the drug formulation itself. Some complex generic formulations (suspensions, ointments, gels) for topical ophthalmic products face impediments to rapid regulatory approval because of the complex nature of the formulations and difficulties in determining bioequivalence with the innovator product. Read More

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December 2018

Non-covalent hitchhiking on endogenous carriers as a protraction mechanism for antiviral macromolecular prodrugs.

J Control Release 2018 Dec 12. Epub 2018 Dec 12.

Department of Chemistry, Aarhus University, 8000 Aarhus C, Denmark. Electronic address:

Albumin is a highly successful tool of drug delivery providing drastically extended body and blood residence time for the associated cargo, but it only traffics single drug copies at a time. In turn, macromolecular prodrugs (MP) are advantaged in carrying a high drug payload but offering only a modest extension of residence time to the conjugated drugs. In this work, we engineer MP to contain terminal groups that bind to albumin via non-covalent association and reveal that this facile measure affords a significant protraction for the associated polymers. Read More

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December 2018

Preparation and drug release property of tanshinone IIA loaded chitosan-montmorillonite microspheres.

Int J Biol Macromol 2018 Dec 12. Epub 2018 Dec 12.

College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, China. Electronic address:

In this study, a biocompatible chitosan/montmorillonite (CS/MMT) composite microsphere was developed as a carrier for loading and sustained-release of the hydrophobic drug of tanshinone IIA. Though the compatibility between hydrophobic drugs and hydrophilic matrix was fairly poor, tanshinone IIA was successfully loaded on the microsphere by the solvent exchange process during chitosan matrix dehydration. The microstructure of the resulting microspheres was characterized with several techniques, such as X-ray diffraction (XRD), thermo-gravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscope (SEM). Read More

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December 2018

LeishInDB: a web-accessible resource for small molecule inhibitors against Leishmania sp.

Acta Trop 2018 Dec 12. Epub 2018 Dec 12.

Department of Molecular Biology/Bioinformatics Centre, Rajendra Memorial Research Institute of Medical Science, Indian Council for Medical Research, Agamkuan, Patna, Bihar 800007. India.

Despite the availability of drugs to treat Leishmaniasis, various other factors including drug resistance and adverse side effects encourage the researchers to search for new strategies and alternatives for treating Leishmaniasis. Repurposing and devising combination therapy with the existing small molecules would serve as an alternative strategy to address the issue, especially the drug resistance. Hence, here we report LeishInDB, a web-accessible resource of small molecule inhibitors having a varying degree of activity towards Leishmania sp. Read More

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December 2018

First report of two consecutive respiratory syncytial virus outbreaks by the novel genotypes ON-1 and NA-2 in a neonatal intensive care unit.

J Pediatr (Rio J) 2018 Dec 12. Epub 2018 Dec 12.

Santa Casa de São Paulo, Unidade de Doenças Infecciosas Pediátricas, São Paulo, SP, Brazil.

Objective: Respiratory syncytial virus is a pathogen frequently involved in nosocomial outbreaks. Although several studies have reported nosocomial outbreaks in neonatal intensive care units, molecular epidemiology data are scarce. Here, the authors describe two consecutive respiratory syncytial virus outbreaks caused by genotypes ON-1 and NA-2 in a neonatal intensive care unit in São Paulo, Brazil. Read More

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December 2018

Effects of proton pump inhibitors on severe haematotoxicity induced after first course of pemetrexed/carboplatin combination chemotherapy.

J Clin Pharm Ther 2018 Dec 15. Epub 2018 Dec 15.

Laboratory of Applied Therapeutics, Center for Education & Research on Clinical Pharmacy, Showa Pharmaceutical University, Tokyo, Japan.

What Is Known And Objective: Pemetrexed/carboplatin combination chemotherapy has shown efficacy as a first-line treatment for advanced non-small-cell lung cancer. However, severe haematotoxicity is often observed during this combination chemotherapy. Some studies have suggested that concomitant drugs may be the risk factors for severe adverse events. Read More

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December 2018

Anatomy of Risk Evaluation and Mitigation Strategies (REMS).

Cancer Treat Res 2019 ;171:93-105

Center for Pharmacoepidemiology and Pharmacoeconomic Research, College of Pharmacy, University of Illinois, Chicago, Illinois, USA.

This Chapter provides an introduction and overview of the U.S. FDA REMS program and applicable regulatory aspects. Read More

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January 2019

The Drug Shortage Crisis in the United States: Impact on Cancer Pharmaceutical Safety.

Cancer Treat Res 2019 ;171:75-92

University of Colorado Denver, Denver, CO, USA.

Drug shortages pose a significant public health concern in the United States, and cancer drugs are among those most affected. Shortages present serious safety risks for patients and substantial burden on providers and the healthcare system. Multifaceted drivers of this complex problem include manufacturing disruptions, raw material shortages, regulatory issues, market dynamics, and limited financial incentives that reward quality and production of off-patent drugs. Read More

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January 2019

The Role of Real-World Evidence in UK Reimbursement: Case Study of Lenalidomide in Myelodysplastic Syndrome Deletion 5q.

Pharmacoecon Open 2018 Dec 14. Epub 2018 Dec 14.

King's College Hospital National Health Service Foundation Trust, London, UK.

Background: Uncertainty within cost-effectiveness analysis, often driven by lack of mature data from large clinical trials, plays a key role in decisions made by the National Institute for Health and Care Excellence (NICE), particularly for early access medicines and orphan drugs.

Objectives: In this case study, we used real-world evidence to address the uncertainty in the cost-effectiveness case for lenalidomide in transfusion-dependent low- and intermediate-1-risk myelodysplastic syndrome (MDS) deletion 5q [del(5q)], affecting a small but unique subpopulation with an orphan disease.

Methods: As part of a submission to NICE, we developed a cost-effectiveness model for lenalidomide, resulting in eventual recommendation. Read More

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December 2018

Recent Progress on Functional Genomics Research of Enterovirus 71.

Virol Sin 2018 Dec 14. Epub 2018 Dec 14.

Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.

Enterovirus 71 (EV71) is one of the main pathogens that causes hand-foot-and-mouth disease (HFMD). HFMD caused by EV71 infection is mostly self-limited; however, some infections can cause severe neurological diseases, such as aseptic meningitis, brain stem encephalitis, and even death. There are still no effective clinical drugs used for the prevention and treatment of HFMD. Read More

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December 2018

Sensitivity of physiological and biochemical endpoints in early ontogenetic stages of crops under diclofenac and paracetamol treatments.

Environ Sci Pollut Res Int 2018 Dec 14. Epub 2018 Dec 14.

Laboratory of Metabolomics and Isotope Analyses, Global Change Research Institute, Czech Academy of Sciences, Bělidla 986/4a, 603 00, Brno, Czech Republic.

Early stages of ontogenesis determining subsequent growth, development, and productivity of crops can be affected by wastewater and sludge contaminated with pharmaceuticals. Diclofenac (DCF) and paracetamol (PCT; both 0.0001 to 10 mg/L) did not affect seed germination and primary root length of onion, lettuce, pea, and tomato. Read More

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December 2018

A nationwide survey of adherence to analgesic drugs among cancer patients in Taiwan: prevalence, determinants, and impact on quality of life.

Support Care Cancer 2018 Dec 14. Epub 2018 Dec 14.

Division of Hematology-Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan.

Purpose: Poor adherence to analgesic drugs is one of the most common barriers to adequate pain management. This prospective, cross-sectional, patient-oriented observational study aimed to explore the adherence rate, clinical factors, and impact of adherence to analgesic drugs on the quality of life (QoL) among cancer outpatients in Taiwan.

Methods: Eight hundred ninety-seven consecutive adult outpatients with cancer who had reported tumor pain and received regular analgesic drug treatment were enrolled from 16 medical centers across Taiwan. Read More

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December 2018

Five-year outcome of children with idiopathic nephrotic syndrome: the NEPHROVIR population-based cohort study.

Pediatr Nephrol 2018 Dec 14. Epub 2018 Dec 14.

Department of Pediatric Nephrology, Hôpital Robert-Debré, APHP, 48 Bd Serurier, 75019, Paris, France.

Background: The optimal therapeutic regimen for children at onset of idiopathic nephrotic syndrome (INS) is still under debate. A better knowledge of the disease's course is necessary to design more appropriate and/or personalized treatment protocols.

Methods: We report the 5-year outcome of patients included from December 2007 to May 2010 in the prospective multicentric and multiethnic population-based NEPHROVIR study. Read More

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December 2018
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Suvorexant (Belsomra Tablets 10, 15, and 20 mg): Japanese Drug-Use Results Survey.

Drugs R D 2018 Dec 14. Epub 2018 Dec 14.

Pharmacovigilance, MSD K.K., Tokyo, Japan.

Background: We report on the results of a Japanese postmarketing drug-use survey of suvorexant (Belsomra) tablets.

Methods: A survey with a ≤ 6-month observation period after the start of administration was conducted, targeting insomnia patients who were treated with suvorexant for the first time in Japan. Information on the safety and efficacy of the drug product was collected. Read More

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December 2018

Variance based global sensitivity analysis of physiologically based pharmacokinetic absorption models for BCS I-IV drugs.

J Pharmacokinet Pharmacodyn 2018 Dec 14. Epub 2018 Dec 14.

Centre for Applied Pharmacokinetic Research, Division of Pharmacy & Optometry, The University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK.

Regulatory agencies have a strong interest in sensitivity analysis for the evaluation of physiologically-based pharmacokinetic (PBPK) models used in pharmaceutical research and drug development and regulatory submissions. One of the applications of PBPK is the prediction of fraction absorbed and bioavailability for drugs following oral administration. In this context, we performed a variance based global sensitivity analysis (GSA) on in-house PBPK models for drug absorption, with the aim of identifying key parameters that influence the predictions of the fraction absorbed and the bioavailability for neutral, acidic and basic compounds. Read More

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December 2018

Radiologic types of Mycobacterium xenopi pulmonary disease: different patients with similar short-term outcomes.

Eur J Clin Microbiol Infect Dis 2018 Dec 14. Epub 2018 Dec 14.

Division of Respirology, Department of Medicine, University of Toronto, Toronto, ON, Canada.

Mycobacterium xenopi pulmonary disease (Mxe-PD) is common among nontuberculous mycobacterial infections in Europe and Canada. Associations between radiological pattern and clinical features and outcomes are inadequately studied in Mxe-PD. We sought to investigate clinical characteristics and outcomes according to the dominant radiological pattern among patients with Mxe-PD. Read More

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December 2018

Niacin, alkaloids and (poly)phenolic compounds in the most widespread Italian capsule-brewed coffees.

Sci Rep 2018 Dec 14;8(1):17874. Epub 2018 Dec 14.

Human Nutrition Unit, Department of Food and Drugs, University of Parma, Parma, Italy.

Coffee is one of the most popular beverages worldwide and, nowadays, one of the most practical way for its preparation is by prepacked capsules. The aim of this study was comparing the content in caffeine, trigonelline, N-methylpyridinium (NMP), niacin, and chlorogenic acids of 65 different capsule-brewed coffees, commercialised by 5 of the most representative brands in Italy. Coffees were prepared from capsules following manufacturer's instructions and analysed with an optimized UHPLC-MS/MS method able to assess all these phytochemicals in one single run. Read More

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December 2018

Development of a highly sensitive enzyme-linked immunosorbent assay (ELISA) through use of poly-protein G-expressing cell-based microplates.

Sci Rep 2018 Dec 14;8(1):17868. Epub 2018 Dec 14.

Ph.D. Program in Clinical Drug Development of Chinese Herbal Medicine, Taipei Medical University, Taipei, Taiwan.

The sensitivity of traditional enzyme-linked immunosorbent assays (ELISAs) is limited by the low binding avidity and heterogeneous orientation of capture antibodies coated on polystyrene-based microplates. Here, we developed a highly sensitive ELISA strategy by fixing poly-protein G-expressing cells on microplates to improve the coating amount and displayed orientation of capture antibodies. One or eight repeated fragment crystallisable (Fc) binding domains of protein G are stably expressed on the surface of BALB/c 3T3 cells (termed 1pG cells or 8pG cells), which then act as highly antibody-trapping microparticles. Read More

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December 2018

Implication for alphavirus host-cell entry and assembly indicated by a 3.5Å resolution cryo-EM structure.

Nat Commun 2018 Dec 14;9(1):5326. Epub 2018 Dec 14.

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, People's Republic of China.

Alphaviruses are enveloped RNA viruses that contain several human pathogens. Due to intrinsic heterogeneity of alphavirus particles, a high resolution structure of the virion is currently lacking. Here we provide a 3. Read More

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December 2018

Drug and disease signature integration identifies synergistic combinations in glioblastoma.

Nat Commun 2018 Dec 14;9(1):5315. Epub 2018 Dec 14.

Center for Therapeutic Innovation, Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, 1120 NW 14th St, Miami, FL, 33136, USA.

Glioblastoma (GBM) is the most common primary adult brain tumor. Despite extensive efforts, the median survival for GBM patients is approximately 14 months. GBM therapy could benefit greatly from patient-specific targeted therapies that maximize treatment efficacy. Read More

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December 2018

Variable gender-dependent platelet responses to combined antiplatelet therapy in patients with stable coronary-artery disease.

J Physiol Pharmacol 2018 Aug 9;69(4). Epub 2018 Dec 9.

Department of Laboratory Diagnostics, Pomeranian Medical University, Szczecin, Poland.

Antiplatelet therapy is considered as a standard procedure against atherosclerotic cardiovscular disease but this therapy has limited effect if resistance to acetylsalicylic acid or clopidogrel is present. Important factors associated with resistance are gender; or inflammation possibly associated with membrane microparticles (MP). It was decided to challenge the hypothesis that differential responses to dual antiplatelet therapy are conditioned by gender and/or proinflammatory status. Read More

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Synthetic cannabinoid hydroxypentyl metabolites retain efficacy at human cannabinoid receptors.

J Pharmacol Exp Ther 2018 Dec 14. Epub 2018 Dec 14.

RTI International;

Synthetic cannabinoids (SCs) are novel psychoactive substances that are easily acquired, widely abused as a substitute for cannabis, and associated with cardiotoxicity and seizures. While the structures of these compounds are based upon scaffolds with known affinity and efficacy at the human cannabinoid type-1 receptor (hCB), upon ingestion or inhalation they can be metabolized to multiple chemical entities of unknown pharmacological activity. A large proportion of these metabolites are hydroxylated on the pentyl chain, a key substituent that determines receptor affinity and selectivity. Read More

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December 2018

Supersaturated silica-lipid hybrid (super-SLH) oral drug delivery systems: Balancing drug loading and in vivo performance.

J Pharmacol Exp Ther 2018 Dec 14. Epub 2018 Dec 14.

University of South Australia;

Supersaturated silica-lipid hybrid (super-SLH) drug carriers are a recent strategy to improve the drug loading of oral solid lipid based formulations, however they are yet to be studied This study investigates the pharmacokinetics (PK) of super-SLH containing ibuprofen (IBU) as a model drug, analysing the influence of supersaturated drug loading on oral bioavailability and assessing correlation (IVIVC). In addition, super-SLH was directly compared to spray dried SLH and Nurofen, to explore its potential advantages over the well-established and commercial formulations. Fasted male Sprague-Dawley rats were administered formulation suspensions (10 mg/kg IBU) via oral gavage and blood samples were acquired and analysed for drug content over 24 hours. Read More

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December 2018

In vivo Preclinical Molecular Imaging of repeated exposure to an NMDA antagonist and a glutaminase inhibitor as potential glutamatergic modulators.

J Pharmacol Exp Ther 2018 Dec 14. Epub 2018 Dec 14.

Molecular Imaging Center Antwerp;

Glutamate is the principal excitatory neurotransmitter in the brain and at the base of a wide variety of neuropathologies, including epilepsy, autism, Fragile X and obsessive compulsive disorder. Glutamate has so become the target for novel drugs in treatment and in fundamental research settings. However, much remains unknown on the working mechanisms of these drugs and the effects of chronic administration on the glutamatergic system. Read More

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December 2018

Clinical effectiveness of pharmacy-led versus conventionally delivered antiviral treatment for hepatitis C in patients receiving opioid substitution therapy: a study protocol for a pragmatic cluster randomised trial.

BMJ Open 2018 Dec 14;8(12):e021443. Epub 2018 Dec 14.

Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.

Introduction: Hepatitis C virus (HCV) infection affects 0.7% of the general population, and up to 40% of people prescribed opioid substitution therapy (OST) in Scotland. In conventional care, less than 10% of OST users are tested for HCV and less than 25% of these initiate treatment. Read More

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December 2018

The antitumor drugs trabectedin and lurbinectedin induce transcription-dependent replication stress and genome instability.

Mol Cancer Res 2018 Dec 14. Epub 2018 Dec 14.

Centro Andaluz de Biología Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla

R-loops are a major source of replication stress, DNA damage and genome instability, which are major hallmarks of cancer cells. Accordingly, growing evidence suggests that R-loops may also be related to cancer. Here we show that R-loops play an important role in the cellular response to trabectedin (ET743), an anticancer drug from marine origin and its derivative lurbinectedin (PM01183). Read More

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December 2018

Combinations of Tyrosine Kinase Inhibitor and ERAD Inhibitor Promote Oxidative Stress-Induced Apoptosis through ATF4 and KLF9 in Medullary Thyroid Cancer.

Mol Cancer Res 2018 Dec 14. Epub 2018 Dec 14.

Department of Endocrine Neoplasia and Hormonal Disorders, MD Anderson Cancer Center.

Medullary thyroid carcinoma (MTC) originates from the C cells of the thyroid gland, which secrete calcitonin. Lymph node and distant metastases are frequently present at diagnosis. Activating mutations of RET, a driver oncogene in MTC that encodes a tyrosine kinase receptor, prevents apoptosis through inhibition of ATF4, a key transcriptional regulator of endoplasmic reticulum (ER) stress. Read More

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December 2018

Genetic variation at the glycosaminoglycan metabolism pathway contributes to the risk of psoriatic arthritis but not psoriasis.

Ann Rheum Dis 2018 Dec 14. Epub 2018 Dec 14.

Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain

Objective: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA. Read More

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December 2018

RGS9-2 rescues dopamine D2 receptor levels and signaling in dystonia mouse models.

EMBO Mol Med 2018 Dec 14. Epub 2018 Dec 14.

Laboratory of Neurophysiology and Plasticity, IRCCS Fondazione Santa Lucia, Rome, Italy

Dopamine D2 receptor signaling is central for striatal function and movement, while abnormal activity is associated with neurological disorders including the severe early-onset dystonia. Nevertheless, the mechanisms that regulate D2 receptor signaling in health and disease remain poorly understood. Here, we identify a reduced D2 receptor binding, paralleled by an abrupt reduction in receptor protein level, in the striatum of juvenile mice. Read More

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December 2018

Catecholaminergic modulation of indices of cognitive flexibility: A pharmaco-tDCS study.

Brain Stimul 2018 Dec 7. Epub 2018 Dec 7.

Department of Psychology, Sociology and Politics, Sheffield Hallam University, Sheffield, UK. Electronic address:

Background: Dopaminergic activity within the dorsolateral prefrontal cortex (dlPFC) has been implicated in the control of cognitive flexibility. Much of the evidence for a causative relationship between cognitive flexibility and dopamine has come from animal studies, whilst human data have largely been correlational.

Objective/hypothesis: The current study examines whether changes in dopamine levels through tyrosine administration and suppression of dlPFC activity via cathodal tDCS could be causally related to cognitive flexibility as measured by task switching and reversal learning. Read More

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December 2018

Complaints addressed by regulatory authorities in drug advertising targeted at consumers: Cases across three, different countries.

Res Social Adm Pharm 2018 Dec 7. Epub 2018 Dec 7.

Department of Health, Social and Clinical Pharmacy, Chung-Ang University College of Pharmacy, Seoul, South Korea; The Graduate School of Pharmaceutical Industry Management, Chung-Ang University, Seoul, South Korea. Electronic address:

Background: Misleading advertisements can affect behavior of both consumers and prescribers and may lead to inappropriate use of medications.

Objective: To analyze the complaints upheld by regulatory authorities in the United Kingdom, Canada, and Australia regarding pharmaceutical advertising directed at consumers.

Methods: Complaints addressed between January 2014 and June 2017 were retrieved from the websites of regulatory authorities. Read More

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December 2018

Comparing patients' prescribed, self-reported, and actual intake of supplemental eicosapentaenoic acid + docosahexaenoic acid.

J Clin Lipidol 2018 Nov 15. Epub 2018 Nov 15.

Atherosclerosis and LDL-Apheresis Center, University of Kansas Medical Center, Kansas City, KS, USA; Division of Clinical Pharmacology, Department of Medicine, University of Kansas Medical Center, Kansas City, KS, USA.

Background: Dietary fish oil supplements containing the omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are frequently used for cardiovascular benefit. However, several factors may limit the intake of prescribed doses.

Objective: The objective of this study is to compare the prescribed, patient self-reported, and actual intake of supplemental EPA + DHA doses in a lipid-specialty clinic and identify common barriers and influences to therapy. Read More

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November 2018

Pro Re Nata Drug Use in Nursing Home Residents: A Systematic Review.

J Am Med Dir Assoc 2018 Dec 11. Epub 2018 Dec 11.

Carl von Ossietzky University Oldenburg, Department of Health Services Research, Oldenburg, Germany.

Objectives: In addition to routinely administered long-term medication, complex drug regimens of nursing home residents often include as needed or pro re nata (PRN) medication. However, there has been no systematic evaluation of the frequency and concomitants of PRN medication in nursing homes. The main objective of this systematic review was to provide a current assessment of PRN drug use in nursing homes. Read More

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December 2018

Identification of novel triazole inhibitors of Wnt/β-catenin signaling based on the Niclosamide chemotype.

Bioorg Med Chem Lett 2018 Nov 12. Epub 2018 Nov 12.

Department of Medicine, Duke University Medical Center, Durham, NC 27710, United States. Electronic address:

Dysregulation of the Wnt signaling pathway is an underlying mechanism in multiple diseases, particularly in cancer. Until recently, identifying agents that target this pathway has been difficult and as a result, no approved drugs exist that specifically target this pathway. We reported previously that the anthelmintic drug Niclosamide inhibits the Wnt/β-catenin signaling pathway and suppresses colorectal cancer cell growth in vitro and in vivo. Read More

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November 2018

Healing the hurt amid the drug war: Narratives of young urban poor Filipinos in recovering families with parental drug use.

Int J Drug Policy 2018 Dec 11. Epub 2018 Dec 11.

Ateneo de Manila University, Philippines. Electronic address:

Background: This qualitative study explores the stories of young urban poor Filipino family members living with recovering parental drug users who turn themselves in to local authorities and completed theKatatagan Kontra Droga sa Komunidad (KKDK). This is a community-based rehabilitation program during the Philippine government's anti-illegal drugs campaign.

Methods: Young urban poor family members living with parental drug use were interviewed (n = 13) and asked to narrate their experiences of parental drug use, surrender, and recovery. Read More

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December 2018
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