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https://www.readbyqxmd.com/read/28647917/novel-endpoints-for-heart-failure-clinical-trials
#1
REVIEW
Carine E Hamo, Mihai Gheorghiade, Javed Butler
PURPOSE OF REVIEW: With the growing prevalence of heart failure, there is a particular need to develop new pharmacologic treatments that can improve outcomes. While there are several approved therapies for heart failure with reduced ejection fraction, there is currently no approved agent for those with preserved ejection fraction. The current review aimed to explore the utility of alternate endpoints to mortality and hospitalization. RECENT FINDINGS: There is increased interest in the use of alternative endpoints such as functional status and quality of life for heart failure drug development to focus on patients feeling better in addition to improving outcomes...
June 24, 2017: Current Heart Failure Reports
https://www.readbyqxmd.com/read/28647517/proteomics-to-study-macrophage-response-to-viral-infection
#2
Tuula A Nyman, Sampsa Matikainen
Viral infections are a major burden to human and animal health. Immune response against viruses consists of innate and adaptive immunity which are both critical for the eradication of the viral infection. The innate immune system is the first line of defense against viral infections. Proper innate immune response is required for the activation of adaptive, humoral and cell-mediated immunity. Macrophages are innate immune cells which have a central role in detecting viral infections including influenza A and human immunodeficiency viruses...
June 21, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28647489/a-high-throughput-assay-to-identify-substrate-selective-inhibitors-of-the-erk-protein-kinases
#3
Chad J Miller, Yagmur Muftuoglu, Benjamin E Turk
Extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylate a variety of substrates important for survival and proliferation, and their activity is frequently deregulated in tumors. ERK pathway inhibitors have shown clinical efficacy as anti-cancer drugs, but most patients eventually relapse due to reactivation of the pathway. One factor limiting the efficacy of current therapeutics is the difficulty in reaching clinically effective inhibition of the ERK pathway in the absence of on-target toxicities...
June 21, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28647378/leishmaniasis-drug-discovery-recent-progress-and-challenges-in-assay-development
#4
REVIEW
Bilal Zulfiqar, Todd B Shelper, Vicky M Avery
Leishmaniasis, caused by the trypanosomatid protozoan Leishmania, is endemic in 98 countries worldwide, with morbidity and mortality increasing daily. Despite available drugs, leishmaniasis faces the challenge of emerging resistance and toxicity concerns for current drug regimes. Identification of anti-leishmanial compounds representing new chemistry and novel mechanisms of action is essential to populate the drug discovery pipeline. The in vitro assays currently available have shown poor translational outcomes, with high compound attrition rates...
June 21, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28647315/safety-and-efficacy-of-new-biodegradable-polymer-based-sirolimus-eluting-stents-in-a-preclinical-model
#5
Armando Pérez de Prado, Claudia Pérez Martínez, Carlos Cuellas Ramón, Marta Regueiro Purriños, María López Benito, José Manuel Gonzalo Orden, José Antonio Rodríguez Altónaga, Rodrigo Estévez Loureiro, Tomás Benito González, David Viñuela Baragaño, María Molina Crisol, Marc Amorós Aguilar, Isabel Pérez Serranos, Arnau Vidal Parreu, Ana Benavides Montegordo, Luis Duocastella Codina, Felipe Fernández Vázquez
INTRODUCTION AND OBJECTIVES: New drug-eluting stents (DES) designed to overcome the limitations of existing devices should initially be tested in preclinical studies. Our objective was to analyze the safety and efficacy of new biodegradable polymer-based DES compared with bare-metal stents (BMS) and commercially available DES in a model of normal porcine coronary arteries. METHODS: We randomly implanted 101 stents (BMS and biodegradable polymer-based sirolimus-eluting stents: 3 test stent iterations [BD1, BD2, and BD3], Orsiro, Biomime and Biomatrix) in the coronary arteries of 34 domestic pigs...
June 21, 2017: Revista Española de Cardiología
https://www.readbyqxmd.com/read/28647107/-justification-of-off-label-antibiotics-uses-in-hospitalized-children
#6
Christelle Berthod, Behrouz Kassaï, Remy Boussageon, Léopold Adelaide, Matthias Jacquet-Lagrèze, Audrey Lajoinie
Unlicensed and off-label (UL/OL) drugs are commonly used in pediatrics wards, especially the antibiotics. It remains unclear if this strategy is justified by randomized controlled trials of good quality? OBJECTIVE: The aim of this study was to compare the level of evidence of UL/OL antibiotics prescription in hospitalized children. The initial hypothesis was that the UL/OL antibiotics prescriptions had a lower level of evidence than licensed antibiotics. METHOD: This observational study assessed the antibiotics prescription in the children mother and women hospital of Lyon...
May 26, 2017: Thérapie
https://www.readbyqxmd.com/read/28647089/reverse-phase-protein-arrays-elucidate-mechanisms-of-action-and-phenotypic-response-in-2d-and-3d-models
#7
REVIEW
Michael Pawlak, Neil O Carragher
The development of new 2D and 3D phenotypic screening assays combined with high-throughput genomic and proteomic technologies are well placed to advance a new era of molecular pathway informed Phenotypic Drug Discovery. We describe the application of Reverse Phase Protein Array (RPPA) technology to elucidate the mechanism-of-action of small molecules at the post-translational pathway level. We propose that profiling of phenotypic hits and lead molecules in increasingly more complex 3D in vitro and ex vivo models at the post-translational pathway network level represents an effective strategy to both triage and progress the preclinical development of phenotypic screening hits...
March 2017: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/28647085/in-vivo-phenotypic-screening-clinical-proof-of-concept-for-a-drug-repositioning-approach
#8
REVIEW
John R Ciallella, Andrew G Reaume
In vivo phenotypic screening and drug repositioning are strategies developed as alternatives to underperforming hypothesis-driven molecular target based drug discovery efforts. This article reviews examples of drugs identified by phenotypic observations and describes the use of the theraTRACE(®)in vivo screening platform for finding and developing new indications for discontinued clinical compounds. Clinical proof-of-concept for the platform is exemplified by MLR-1023, a repositioned compound that has recently shown significant clinical efficacy in Type 2 diabetes patients...
March 2017: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/28647083/the-production-of-3d-tumor-spheroids-for-cancer-drug-discovery
#9
REVIEW
Shilpa Sant, Paul A Johnston
New cancer drug approval rates are ≤5% despite significant investments in cancer research, drug discovery and development. One strategy to improve the rate of success of new cancer drugs transitioning into the clinic would be to more closely align the cellular models used in the early lead discovery with pre-clinical animal models and patient tumors. For solid tumors, this would mandate the development and implementation of three dimensional (3D) in vitro tumor models that more accurately recapitulate human solid tumor architecture and biology...
March 2017: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/28647082/targeting-neuronal-function-for-cns-drug-discovery
#10
REVIEW
Chris M Hempel, Christopher A Werley, Graham T Dempsey, David J Gerber
There is a pressing need for new and more effective treatments for central nervous system (CNS) disorders. A large body of evidence now suggests that alterations in synaptic transmission and neuronal excitability represent underlying factors for many neurological and psychiatric diseases. However, it has been challenging to target these complex functional domains for therapeutic discovery using traditional neuronal assay methods. Here we review advances in neuronal screening technologies and cellular model systems that enable phenotypic screening of neuronal function as a basis for novel CNS drug discovery approaches...
March 2017: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/28646952/drug-resistant-tuberculosis-primary-transmission-and-management
#11
Alexander C Outhred, Philip N Britton, Ben J Marais
The DOTS strategy assisted global tuberculosis (TB) control, but was unable to prevent the emergence and spread of drug-resistant strains. Genomic evidence confirms the transmission of drug-resistant Mycobacterium tuberculosis strains in many different settings, indicative of epidemic spread. These findings emphasise the need for enhanced infection control measures in health care and congregate settings. Young children in TB endemic areas are particularly vulnerable. Although advances in TB drug and vaccine development are urgently needed, improved access to currently available preventive therapy and treatment for drug resistant TB could reduce the disease burden and adverse outcomes experienced by children...
June 2017: Journal of Infection
https://www.readbyqxmd.com/read/28646810/synergistic-anti-breast-cancer-effects-of-combined-treatment-with-oleuropein-and-doxorubicin-in-vivo
#12
Maha H Elamin, Abdelsalam B Elmahi, Maha H Daghestani, Ebtesam M Al-Olayan, Reem A Al-Ajmi, Afrah F Alkhuriji, Sherifa S Hamed, Manal F Elkhadragy
Context • Breast cancer is a leading cause of cancer fatalities among women worldwide. Of the more than 80% of patients who receive adjuvant chemotherapy, approximately 40% relapse. The majority of these patients die of disseminated metastatic disease, which emphasizes the need for new therapeutic strategies Objective • The study intended to investigate the anticancer effects of oleuropein (OL) and doxorubicin (DOX) individually and in combination on breast tumor xenografts and also to evaluate the molecular pathways involved...
June 23, 2017: Alternative Therapies in Health and Medicine
https://www.readbyqxmd.com/read/28646789/data-mining-for-detecting-signals-of-adverse-drug-reactions-of-fluoxetine-using-the-korea-adverse-event-reporting-system-kaers-database
#13
Seonji Kim, Kyounghoon Park, Mi-Sook Kim, Bo Ram Yang, Hyun Jin Choi, Byung-Joo Park
Selective serotonin reuptake inhibitors (SSRIs) have become one of the most broadly used medications in psychiatry. Fluoxetine is the first representative antidepressant SSRI drug approved by the Food and Drug Administration (FDA) in 1987. Safety information on fluoxetine use alone was less reported than its combined use with other drugs. There were no published papers on adverse drug reactions (ADRs) of fluoxetine analyzing spontaneous adverse events reports. We detected signals of the adverse drug reactions of fluoxetine by data mining using the Korea Adverse Events Reporting System (KAERS) database...
June 13, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28646755/bio-fabrication-of-catalytic-platinum-nanoparticles-and-their-in-vitro-efficacy-against-lungs-cancer-cells-line-a549
#14
Sadeeq Ullah, Aftab Ahmad, Aoke Wang, Muslim Raza, Amin Ullah Jan, Kamran Tahir, Aziz Ur Rahman, Yuan Qipeng
Platinum based drugs are considered as effective agents against various types of carcinoma; however, the severe toxicity associated with the chemically prepared platinum complexes limit their practical applications. Similarly, water pollution caused by various organic moieties is another serious health problem worldwide. Hence, an intense need exists to develop new, effective and biocompatible materials with catalytic and biomedical applications. In the present contribution, we prepared platinum nanoparticles (PtNPs) by a green route using phytochemicals as a source of reducing and stabilizing agents...
June 16, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28646742/image-analysis-for-tsh-mrna-in-situ-hybridization-in-pituitary-glands-from-rats-with-thyroid-follicular-cell-hypertrophy-after-treatment-with-three-different-test-compounds
#15
Juergen Funk, Martin Ebeling, Thomas Singer, Christian Landes
The goal of this in situ hybridization and image analysis technique is to study the effects of new pharmacological/chemical entities on the thyroid and pituitary gland in rats, reveal the pathogenesis of thyroid follicular cell hypertrophy and to retrospectively exclude the risk of thyroid tumor development in humans. In the present study, we describe the increase of thyroid-stimulating hormone- (TSH-) beta subunit mRNA in the pars distalis of the pituitary gland and the quantitative measurement of TSH mRNA positive cells from rats of three 4-week toxicity studies treated with three different test compounds inducing thyroid follicular cell and hepatocellular hypertrophy in rats...
June 11, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28646703/comparison-of-type-2-diabetes-prevalence-in-chinese-migrants-vs-caucasians-and-new-perspectives-for-screening-of-cerebrovascular-disease-in-chinese-a-proof-of-concept-study
#16
Pietro A Modesti, Sergio Castellani, Maria Calabrese, Danilo Malandrino, Dong Zhao
AIMS: Type 2 diabetes (T2DM) is a recognized risk factor for intracranial stenosis (ICS) in China where ischemic stroke is a health priority. In Europe little information is available on T2DM prevalence among Chinese minority groups and vascular screening is commonly limited to extracranial vessels. Feasibility of community-based T2DM screening, differences in T2DM prevalence between Chinese migrants and Italians, and prevalence of ICS among Chinese patients with newly diagnosed T2DM were investigated...
June 13, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28646658/investigation-and-structural-elucidation-of-a-new-impurity-in-bulk-drug-of-cilostazol-by-lc-ms-ms-ft-ir-and-nmr
#17
Zhaoxia Hu, Sanguo Gao, Jue Gao
A new impurity was detected in bulk cilostazol (CIL) crude during routine analysis. The impurity (∼4%, the specification for unknown impurity in crude is not more than 0.20%) has a relative retention time of 1.46. Based on MS, NMR and IR spectral data, the impurity was identified as 6,6'-bis(4-(1-cyclohexyl-1H-tetrazol-5-yl) butoxy)-3,3',4,4'-tetrahydro-[7,7'-biquinoline]-2,2'(1H,1'H)-dione(CIL-dimer). The precursor of CIL-dimer is an oxidative product of starting material 6-Hydroxy-3,4-dyhydro-1H-quinolin-2-one(6-HQ), CIL-dimer was formed in the following reaction with 5-(3-Chloro-propyl)-1-cyclohexyl-1H-tetrazol(CHCBT)...
June 15, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28646446/innovations-in-the-endovascular-management-of-critical-limb-ischemia-retrograde-tibiopedal-access-and-advanced-percutaneous-techniques
#18
REVIEW
Jihad A Mustapha, Larry J Diaz-Sandoval, Fadi Saab
PURPOSE OF REVIEW: Retrograde tibiopedal access and interventions have contributed to advance of endovascular techniques to treat critical limb ischemia (CLI) patients. This review encompasses the spectrum from advanced diagnostic imaging and technical therapeutic approaches for infrapopliteal occlusions, to a discussion of current standards and future directions. RECENT FINDINGS: Contemporary studies of infrapopliteal angioplasty show suboptimal short-term and 1-year clinical outcomes...
August 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28646254/cytoprotective-effects-of-diallyl-trisulfide-against-valproate-induced-hepatotoxicity-new-anticonvulsant-strategy
#19
Ahmed A Shaaban, Dina S El-Agamy
Sodium valproate (VP) is an important antiepileptic drug, although it can produce deleterious hepatotoxic reactions. Diallyl trisulfide (DATS) is the principle component of garlic oil that possesses antioxidant properties. This study explored the potential hepatoprotective activity of DATS against VP-induced hepatic damage and its underlying mechanisms. In addition, the study assessed the effect of DATS on VP antiepileptic activity. Rats were given DATS once daily at two different doses along with VP for 2 weeks...
June 23, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28646180/sustained-release-from-a-metal-analgesics-entrapped-within-biocidal-silver
#20
Barak Menagen, Rami Pedahzur, David Avnir
Matrices for sustained release of drugs have been based on polymers, biomaterials and oxides. The use of the major family of metals as matrices for sustained release is, to the best of our knowledge, unknown. In this context we describe a new family of bio-composites for sustained release of drugs, namely analgesic drugs entrapped within metallic silver. Synthetic methodologies were developed for the preparation of ibuprofen@Ag, naproxen@Ag, tramadol@Ag and bupivacaine@Ag composites. Detailed kinetic analysis of the release of the drugs from within the metal, is provided, demonstrating that metals can indeed serve as reservoirs for drug release...
June 23, 2017: Scientific Reports
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