1,418,047 results match your criteria Drugs in R&D[Journal]


Nonalcoholic-Fatty-Liver-Disease and Nonalcoholic Steatohepatitis: Successful Development of Pharmacological Treatment Will Depend on Translational Research.

Digestion 2018 Dec 7:1-7. Epub 2018 Dec 7.

Background: Nonalcoholic-fatty-liver-disease/nonalcoholic steatohepatitis (NAFLD/NASH) is expected to become the leading liver disease worldwide. Typical liver-related complications are fibrosis, cirrhosis, and the development of hepatocellular cancer (HCC) with the need for liver transplantation. Up to now there is no approved pharmacotherapy. Read More

View Article
December 2018

Recruitment of macrophages and bone marrow stem cells to regenerating liver promoted by sodium phthalhydrazide in mice.

Biomed Pharmacother 2018 Dec 8;110:594-601. Epub 2018 Dec 8.

Institute of Immunopathology and Preventive Medicine, Povsetova ulica 29, 1000 Lublana, Slovenia. Electronic address:

Pharmacological interventions which could be hepatoprotective, depending on bioavailability, anti-inflammatory and macrophage-targeting potential of drugs, are still at early preclinical stages. Existing evidence from many animal models of liver injury, as well as from human data, indicate that pharmacological and/or phytochemical interventions have limited impact on liver recovery. Recent studies on stem cell therapies focused on different cell subsets involved in tissue repair, including monocytes/macrophages and bone marrow cells migrating to the injured liver. Read More

View Article
December 2018
1 Read

Kojic acid applications in cosmetic and pharmaceutical preparations.

Biomed Pharmacother 2018 Dec 8;110:582-593. Epub 2018 Dec 8.

Student Research Committee, Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address:

Skin color disorders can be caused by various factors, such as excessive exposure to sunlight, aging and hormonal imbalance during pregnancy, or taking some medications. Kojic acid (KA) is a natural metabolite produced by fungi that has the ability to inhibit tyrosinase activity in synthesis of melanin. The major applications of KA and its derivatives in medicine are based on their biocompatibility, antimicrobial and antiviral, antitumor, antidiabetic, anticancer, anti-speck, anti-parasitic, and pesticidal and insecticidal properties. Read More

View Article
December 2018
1 Read

Piezoelectric barium titanate nanostimulators for the treatment of glioblastoma multiforme.

J Colloid Interface Sci 2018 Dec 4;538:449-461. Epub 2018 Dec 4.

Istituto Italiano di Tecnologia, Smart Bio-Interfaces, Viale Rinaldo Piaggio 34, 56025 Pontedera, Italy; Politecnico di Torino, Department of Mechanical and Aerospace Engineering, Corso Duca degli Abruzzi 24, 10129 Torino, Italy. Electronic address:

Major obstacles to the successful treatment of gliolastoma multiforme are mostly related to the acquired resistance to chemotherapy drugs and, after surgery, to the cancer recurrence in correspondence of residual microscopic foci. As innovative anticancer approach, low-intensity electric stimulation represents a physical treatment able to reduce multidrug resistance of cancer and to induce remarkable anti-proliferative effects by interfering with Ca and K homeostasis and by affecting the organization of the mitotic spindles. However, to preserve healthy cells, it is utterly important to direct the electric stimuli only to malignant cells. Read More

View Article
December 2018

Measurements and correlations in solution-state for charge transfer products caused from the 1:2 complexation of TCNE acceptor with several important drugs.

Spectrochim Acta A Mol Biomol Spectrosc 2018 Dec 5;211:166-177. Epub 2018 Dec 5.

Department of Chemistry, Faculty of Science, Taif University, Al-Haweiah, P.O. Box 888, 21974 Taif, Saudi Arabia; Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, Egypt.

In our previous work, we highlighted the thermodynamic and spectroscopic characteristics of the 1:1 charge transfer (CT) complexation of TCNE acceptor with various medically important drugs. Continuing that work, we further examine drugs that react with the TCNE acceptor via a 1:2 interaction. The examined drugs are atenolol, quinidine, cimetidine, reserpine, and levofloxacin. Read More

View Article
December 2018

Enantioselective LC-MS/MS for anthropogenic markers of septic tank discharge.

Chemosphere 2018 Dec 3;219:191-201. Epub 2018 Dec 3.

School of Pharmacy and Life Sciences, Robert Gordon University, Aberdeen, AB10 7GJ, UK. Electronic address:

Households in rural locations utilize septic tanks for wastewater treatment and can cause surface water contamination. A new methodology was developed to help investigate the role septic tanks play in the dissemination of prescription and over-the-counter drugs, personal care products and stimulants in the aqueous environment. Simultaneous analysis of 16 chiral and achiral anthropogenic markers was achieved using a Chirobiotic V2 enantioselective column in polar ionic mode. Read More

View Article
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

View Article
December 2018
1 Read

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

View Article
December 2018

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

View Article
December 2018

Chemical composition, antioxidant activities of polysaccharide from Pine needle (Pinus massoniana) and hypolipidemic effect in high-fat diet-induced mice.

Int J Biol Macromol 2018 Dec 8. Epub 2018 Dec 8.

Jiangxi Key Laboratory of Natural Product and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang 330045, China. Electronic address:

The aim of this study is to investigate hypolipidemic and antioxidant effects of Pine needle polysaccharide (PNP) from Pinus massoniana in high-fat diet (HFD)-induced mice. PNP could significantly improve the serum lipid levels (total cholesterol, triacylglycerols, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol), enhance the antioxidant enzymes levels (total antioxidant capability, superoxide dismutase, glutathione peroxidase, catalase), and decrease malondialdehyde (MDA) content in HFD-induced mice. PNP exhibited distinct antioxidant ability on the superoxide anions, 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and ferric ion reducing antioxidant power (FRAP) in vitro. Read More

View Article
December 2018

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

View Article
December 2018

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

View Article
December 2018

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

View Article
December 2018

Adalimumab efficacy for venous thrombosis in typical sites in Behçet's syndrome.

Arthritis Rheumatol 2018 Dec 7. Epub 2018 Dec 7.

Department of Neurosciences, Psychology, Pharmacology and Child Health (NEUROFARBA), University of Firenze, Italy.

In our work entitled "Adalimumab-based treatment versus DMARDs for venous thrombosis in Behçet syndrome. A retrospective study of 70 patients with vascular involvement" , we showed that Adalimumab (ADA)-based regimen is more effective and rapid than disease modifying anti-rheumatic drugs (DMARDs) in inducing resolution of venous thrombosis in patients with Behçet syndrome (BS), also allowing significant reduction of steroid exposure. This article is protected by copyright. Read More

View Article
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

View Article
December 2018

Oleoylethanolamide: A novel pharmaceutical agent in the management of obesity-an updated review.

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

Department of Nutrition, Nutrition Research Center, Faculty of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran.

Obesity as a multifactorial disorder has been shown a dramatically growing trend recently. Besides genetic and environmental factors, dysregulation of the endocannabinoid system tone is involved in the pathogenesis of obesity. This study reviewed the potential efficacy of Oleoylethanolamide (OEA) as an endocannabinoid-like compound in the energy homeostasis and appetite control in people with obesity. Read More

View Article
December 2018
1 Read

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

View Article
December 2018

Effects of inhibitors of the renin-angiotensin system on reducing blood pressure and expression of inflammatory factors in CHD patients: A network meta-analysis.

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

First Cadres Ward, The First Affiliated Hospital of PLA General Hospital, Beijing, China.

The renin-angiotensin system (RAS) is an ever-evolving endocrine system with considerable checks and balances on the production and catabolism of angiotensin peptides most likely due to the manifold effects of angiotensins. We aimed to explore the effects of different inhibitors of RAS on blood pressure and expression of inflammatory factors in patients with coronary heart disease (CHD). We initially searched PubMed, EMBASE and Cochrane Library electronic databases with nine eligible randomized controlled trials enrolled. Read More

View Article
December 2018
1 Read

Synthesis and characterization of novel substituted thiophene derivatives and discovery of their carbonic anhydrase and acetylcholinesterase inhibition effects.

J Biochem Mol Toxicol 2018 Dec 10:e22261. Epub 2018 Dec 10.

Department of Chemistry, Faculty of Science, Ataturk University, Erzurum, Turkey.

Novel substituted thiophene derivatives (1, 2a-e, 3, and 4) were synthesized and their structures were characterized by infrared radiation, nuclear magnetic resonance, and mass analysis. These novel substituted thiophene derivatives were effective inhibitor compounds of the carbonic anhydrase I and II isozymes (hCA I and II), and acetylcholinesterase (AChE) enzyme with K values in the range of 447.28 to 1004. Read More

View Article
December 2018
1.925 Impact Factor

Significant antitumor effect of an antibody against TMEM180, a new colorectal cancer-specific molecule.

Cancer Sci 2018 Dec 8. Epub 2018 Dec 8.

Division of Developmental Therapeutics, Exploratory Oncology Research & Clinical Trial Centre, National Cancer Centre, Kashiwa, Chiba, 277-8577, Japan.

The present state of therapy for colorectal cancer (CRC) is far from satisfactory, highlighting the need for new targets for this disease. We identified a new colorectal cancer (CRC)-specific molecule, TMEM180, a predicted eleven-pass transmembrane protein that apparently functions as a cation symporter. We developed the anti-TMEM180 monoclonal antibody (mAb) and then succeeded in humanizing the mAb. Read More

View Article
December 2018
1 Read

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

View Article
December 2018
1 Read

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

View Article
December 2018

Detection of Brodifacoum and other Rodenticides in Drug Mixtures using Thermal Desorption Direct Analysis in Real Time Mass Spectrometry (TD-DART-MS).

J Forensic Sci 2018 Dec 10. Epub 2018 Dec 10.

National Institute of Standards and Technology, 100 Bureau Drive, MS 8371, Gaithersburg, MD, 20899.

In recent months, there has been increased reporting of seized drug and toxicology cases containing rodenticides, the active ingredient in rat poisons. Seeing as rodenticides are not scheduled substances, they are not commonly screened for in seized drug analysis. This work investigates the use of TD-DART-MS for the simultaneous detection of rodenticides and drugs. Read More

View Article
December 2018

Therapeutic potential of nvp-bkm120 in human osteosarcomas cells.

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

Department of Biomedical Sciences, University of Bologna, Bologna, Italy.

Osteosarcoma (OS) is the most common pediatric malignant neoplasia of the skeletal system. It is characterized by a high degree of malignancy and a severe tendency to metastasize. In the past decade, many studies have provided evidence that the phosphoinositide 3-kinase (PI3K) signaling pathway is one of the most frequently altered pathways in human cancer, and has a critical role in driving tumor initiation and progression. Read More

View Article
December 2018

The effects of incretin-based therapies on beta-cell function and insulin resistance in type 2 diabetes: a systematic review and network meta-analysis combining 360 trials.

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

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.

Aim: To evaluate the comparative effects of incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 inhibitors (DPP-4Is), on beta-cell function and insulin resistance in patients with type 2 diabetes mellitus (T2DM).

Materials And Methods: Medline, Embase, the Cochrane Library and www.clinicaltrials. Read More

View Article
December 2018

Diacylglycerol kinase α-selective inhibitors induce apoptosis and reduce viability of melanoma and several other cancer cell lines.

J Cell Biochem 2018 Dec 9. Epub 2018 Dec 9.

Department of Chemistry, Graduate School of Science, Chiba University, Chiba, Japan.

Diacylglycerol (DG) kinase (DGK), which phosphorylates DG to generate phosphatidic acid (PA), consists of ten isozymes (α-к). Recently, we identified a novel small molecule inhibitor, CU-3, that selectively inhibits the activity of the α isozyme. In addition, we newly obtained Compound A, which selectively and strongly inhibits type I DGKs (α, β, and γ). Read More

View Article
December 2018

Protective effects of plant-derived natural products on renal complications.

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

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

Diabetic nephropathy is the leading cause of renal failure worldwide. This debilitating disorder has several underlying pathophysiologic mechanisms, and therefore a variety of pharmacologic agents have been developed to prevent or treat diabetic nephropathy; however, synthetic drugs may possess unfavorable side effects. In response to this, the global use of herbal-based pharmacologic agents is increasing among diabetic patients. Read More

View Article
December 2018

Single-Dose Pharmacokinetic Properties and Relative Bioavailability of Different Formulations of Posaconazole Oral Suspension in Healthy Volunteers.

Clin Pharmacol Drug Dev 2018 Dec 10. Epub 2018 Dec 10.

University of Zagreb, Faculty of Pharmacy and Biochemistry, Department of Pharmaceutical Technology, Zagreb, Croatia.

The rate and extent of absorption of drugs belonging to Biopharmaceutics Classification System class II are rate-limited by dissolution and highly dependent on the performance of the formulated product. The purpose of the present study was to investigate the potential impact of a surfactant and the particle size of the active substance on the in vitro drug dissolution profiles and in vivo pharmacokinetics of the poorly soluble drug posaconazole. A comparative physicochemical evaluation was conducted, and 3 formulations of posaconazole oral suspension were tested in various dissolution media compared with the reference product. Read More

View Article
December 2018

Quality, bioactivity study, and preclinical acute toxicity, safety pharmacology evaluation of PEGylated recombinant human endostatin (M ES).

J Biochem Mol Toxicol 2018 Dec 10:e22257. Epub 2018 Dec 10.

National Engineering Laboratory for Anti-Tumor Protein Therapeutics, School of Life Sciences, Tsinghua University, Beijing, China.

Endostar, a potent endogenous antiangiogenic factor, is wildly used in clinics. However, it was easily degraded by enzymes and rapidly cleared by the kidneys. To overcome these shortcomings, PEGylated recombinant human endostatin was developed. Read More

View Article
December 2018

A chemogenetic approach for treating experimental Parkinson's disease.

Mov Disord 2018 Dec 10. Epub 2018 Dec 10.

The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

Background: PD is a common neurodegenerative disease primarily affecting the cortico-basal ganglia loop.

Objective: To investigate whether chemogenetic-mediated neuromodulation of various nuclei and pathways can counterbalance basal ganglia network abnormalities and improve motor disability in experimental PD.

Methods: Experimental PD was induced by stereotactic injection of 6-OHDA to the medial forebrain bundle. Read More

View Article
December 2018

Strategies toward rheumatoid arthritis therapy; the old and the new.

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

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Currently, medications used to treat rheumatoid arthritis (RA) are glucocorticoids (GCs) and nonsteroidal anti-inflammatory drugs (NSAIDs), predominantly used for controlling the pain and inflammation, disease-modifying antirheumatic drugs (DMARDs), administered as first-line medication for newly diagnosed RA cases, and biological therapies, used to target and inhibit specific molecules of the immune and inflammatory responses. NSAIDs and other GCs are effective in alleviating the pain, inflammation, and stiffness due to RA. DMARDs that are used for RA therapy are hydroxychloroquine, methotrexate, leflunomide, and sulfasalazine. Read More

View Article
December 2018
1 Read

Ultra high performance liquid chromatography with tandem mass spectrometry method for determination of four compounds in rat plasma after oral administration of Xanthii fructus and stir-fried Xanthii fructus extracts.

Biomed Chromatogr 2018 Dec 9:e4464. Epub 2018 Dec 9.

Engineering Center of State Ministry of Education for Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing, China.

Xanthii fructus (XF), the fruit of Xanthium sibiricum Patr. is a traditional Chinese materia medica commonly used to treat allergic rhinitis (AR) and other rhinitis diseases. To uncover the mechanism of stir frying process and its effect on pharmacokinetic behavior of active compounds in model rats, four active compounds including chlorogenic acid, 4-caffeoylquinic acid, 1,5-O-dicaffeoylquinic acid and apigenin were selected based on previous spectrum-effect experiments. Read More

View Article
December 2018

Near IR Photochemistry for Biology: Exploiting the Optical Window of Tissue.

Photochem Photobiol 2018 Dec 7. Epub 2018 Dec 7.

Department of Chemistry, Massachusetts Institute of Technology.

Photoactive molecules enable much of modern biology and biochemistry - a vast library of fluorescent chromophores is used to track and label cellular structures and macromolecules. However, photochemistry is better-known to the synthetic or physical organic chemist as a "light switch" that turns on unusual excited-state reactivity, isomerization, or dynamic adjustment of structure. This review details a rapidly growing approach to bio-photochemistry that uses low-energy near-IR wavelengths not only for imaging, but for close spatial control over chemical switching events in biosystems. Read More

View Article
December 2018

Relevance of Polypharmacy for Clinical Outcome in Patients Receiving Vitamin K Antagonists.

J Am Geriatr Soc 2018 Dec 11. Epub 2018 Dec 11.

Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Background: Although polypharmacy is associated with a negative clinical outcome in various settings and commonly observed in patients receiving oral anticoagulation therapy, evidence on the relevance for the clinical outcome of anticoagulated patients is currently limited. The aim of the study was to investigate the effect of polypharmacy on the clinical outcomes among patients taking phenprocoumon.

Design: Prospective cohort study. Read More

View Article
December 2018
2 Reads

The Role of the Phosphorus Atom in Drug Design.

ChemMedChem 2018 Dec 11. Epub 2018 Dec 11.

Universidad de Buenos Aires, Química Orgánica, Pab 2, Piso 3, Ciudad Universitaria, C1428EHA, Buenos Aires, ARGENTINA.

Although the phosphorus atom is found in a variety of oxidation states, most of the phosphorus-containing molecules of pharmacological important possess this phosphorus atom as a phosphonate or a phosphinate functional moiety or, in a major oxidation state, as a phosphate group. The major occurrence of phosphorus in drugs is either in prodrugs or in molecules where the phosphorus atom has a role in its biological action such as: in modified nucleotides, in metabolically stable analogues of metabolites bearing phosphate groups, as bioisosteric analogues of carboxyl groups, etc. Read More

View Article
December 2018

Ethics codes and use of new and innovative drugs.

Br J Clin Pharmacol 2018 Dec 9. Epub 2018 Dec 9.

Department of Clinical Immunology, Medical University of Warsaw, Nowogrodzka Str. 59, 02-006, Warsaw, Poland.

Treatment with new and/or innovative drugs with uncertain safety and efficacy profile is associated with substantial ethical concerns. The main objective of this paper is to present guidance on the use of such drugs contained in: 1) major international codes and guidelines pertaining to medical ethics and biomedical research; 2) national codes of medical ethics and professional conduct of the US, Canada, Australia, New Zealand, the UK, Ireland, France and Germany. Out of the four international codes and guidelines analyzed, only the Declaration of Helsinki addresses the question of the use of unproven drugs. Read More

View Article
December 2018

Simvastatin and the Rho-kinase inhibitor Y-27632 prevent myofibroblast transformation in Peyronie's disease-derived fibroblasts via inhibition of YAP/TAZ nuclear translocation.

BJU Int 2018 Dec 9. Epub 2018 Dec 9.

Laboratory of Experimental Urology, Department of Development and Regeneration, KU, Leuven, Belgium.

Objectives: To uncover the anti-myofibroblast (MFB) properties of Rho-kinase inhibitor (compound Y-27632) and simvastatin in an in vitro model of Peyronie's disease (PD). PD is a sexual debilitating disease caused by an irreversible fibrotic plaque in the penile tunica albuginea (TA). Treatment is limited to surgically restoring anatomical shape. Read More

View Article
December 2018

Synthesis and biological evaluation of substituted indole and its analogs as influenza A virus inhibitors.

Chem Biodivers 2018 Dec 9. Epub 2018 Dec 9.

: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China, CHINA.

Influenza A virus (IAV), a highly pathogenic virus to human beings, is most susceptible to mutation and thus causes rapid, severe global pandemics resulting in millions of fatalities worldwide. Since resistance to the existing anti-influenza drugs is developing, innovative inhibitors with a different mode of action are urgently needed. The lead compound 6092B-E5 has proven to be an effective antiviral reagent in our previous work. Read More

View Article
December 2018

Hypoxia-inducible factor-2α directly promotes BCRP expression and mediates the resistance of ovarian cancer stem cells to adriamycin.

Mol Oncol 2018 Dec 10. Epub 2018 Dec 10.

Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning Province, China.

Ovarian cancer stem cells (OCSCs) are sources of tumor chemoresistance and recurrence. A hypoxic microenvironment contributes to the chemoresistance of cancer stem cells (CSCs), but the underlying mechanism is not fully understood yet. Here, we show that increased HIF-2α expression is associated with enhanced stemness of OCSCs and poor outcomes in ovarian cancer patients. Read More

View Article
December 2018

The K 7 channel activator retigabine suppresses mouse urinary bladder afferent nerve activity without affecting detrusor smooth muscle K channel currents.

J Physiol 2018 Dec 7. Epub 2018 Dec 7.

Department of Pharmacology, University of Vermont, Burlington, VT, 05405.

Key Points Summary: K 7 channels are a family of voltage-dependent K channels expressed in many cell types, which open in response to membrane depolarization to regulate cell excitability. Drugs that target K 7 channels are used clinically to treat epilepsy. Interestingly, these drugs also cause urinary retention, but it was unclear how. Read More

View Article
December 2018

Palladium- and Rhodium-Catalyzed Dynamic Kinetic Resolution of Racemic Internal Allenes Towards Chiral Pyrazoles.

Angew Chem Int Ed Engl 2018 Dec 10. Epub 2018 Dec 10.

GERMANY.

A complementing Pd- and Rh-catalyzed dynamic kinetic resolution (DKR) of racemic allenes leading to N-allylated pyrazoles is described. Such compounds are of enormous interest in medicinal chemistry as certified drugs and potential drug candidates. The new methods feature high chemo-, regio- and enantioselectivities aside from displaying a broad substrate scope and functional group compatibility. Read More

View Article
December 2018

Antiresorptive Agents' Bone-protective and Adjuvant Effects in Postmenopausal Women with Early Breast Cancer.

Br J Clin Pharmacol 2018 Dec 11. Epub 2018 Dec 11.

Endocrinology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.

Potent antiresorptive drugs (bisphosphonate and denosumab) are often used to protect bone health in postmenopausal breast cancer patients. In addition, clinical trials have shown that these drugs increase disease-free survival, though the mechanism of adjuvant benefit is largely unknown. Here we review the bone health and adjuvant data for both classes of antiresorptive drugs and highlight differences in their pharmacology. Read More

View Article
December 2018

The American Headache Society Position Statement On Integrating New Migraine Treatments Into Clinical Practice.

Authors:

Headache 2018 Dec 10. Epub 2018 Dec 10.

Objective: To provide healthcare professionals with updated guidance in the use of novel preventive and acute treatments for migraine in adults.

Background: The principles of preventive and acute pharmacotherapy for patients with migraine have been outlined previously, but the emergence of new technologies and treatments, as well as new formulations of previously established treatments, has created a need for an updated guidance on the preventive and acute treatment of migraine.

Methods: This statement is based on a review of existing guidelines and principles for preventive and acute treatment of migraine, as well as the results of recent clinical trials of drugs and devices for these indications. Read More

View Article
December 2018

[Pathophysiology of the glutamate and the glycine transporters: new therapeutic targets].

Rev Neurol 2018 Dec;67(12):491-504

Centro de Biologia Molecular Severo Ochoa. Universidad Autonoma de Madrid, Madrid, Espana.

Introduction: The amino acids glutamate and glycine, apart from their role in protein synthesis, are two fundamental neurotransmitters in the central nervous system of mammals. The first one is ubiquitous and is involved in excitatory pathways of the neocortex, the retina and the cerebellum, and the second is involved in inhibitory pathways of brain caudal areas. However, both share their way of acting by integrating into the functioning of glutamate receptors of the NMDA type fundamentals in the regulation of motor, sensory and cognitive systems. Read More

View Article
December 2018
1 Read

Risk of cancer after assisted reproduction: a review of the available evidences and guidance to fertility counselors.

Eur Rev Med Pharmacol Sci 2018 Nov;22(22):8042-8059

Gynecological Oncology, National Cancer Institute, Aviano, Italy.

Objective: Infertile women requiring ovarian stimulation and assisted reproduction techniques (ART) are faced with difficult issues. The fear that using hormones could increase their risk of cancer is the most significant. One of the main challenges for assessing cancer risk after ART is the difficulty to separate it from the underlying condition of infertility per se. Read More

View Article
November 2018
  • Page 1 of 28361