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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/28647801/prognostic-factors-of-atrial-fibrillation-following-coronary-artery-bypass-graft-surgery
#2
Mantas Kievišas, Vytenis Keturakis, Egidijus Vaitiekūnas, Lukas Dambrauskas, Loreta Jankauskienė, Šarūnas Kinduris
OBJECTIVE: Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery. To prevent this complication, routine pharmacological prophylactic drugs could be administered. Our study aimed to analyze the various perioperative factors associated with the development of POAF after coronary artery bypass graft (CABG) surgery. METHODS: This prospective study included 617 patients, who received CABG surgery in the year 2014. RESULTS: There were 429 (69...
June 24, 2017: General Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28647791/premonitory-symptoms-of-migraine-in-childhood-and-adolescence
#3
REVIEW
N Karsan, P Prabhakar, P J Goadsby
PURPOSE OF REVIEW: Premonitory symptoms in migraine; symptoms occurring before the onset of migraine pain or aura, are an increasingly recognised area of interest within headache research. It has been recently documented in the literature that these symptoms also occur in children and adolescents, with a comparable phenotype to adults. This review discusses the wide presentation of premonitory symptoms in migraine in children and adolescents, and the importance of understanding how these early symptoms are mediated in order to ensure that targeted abortive therapies are developed in the future...
July 2017: Current Pain and Headache Reports
https://www.readbyqxmd.com/read/28647672/therapeutic-targeting-of-nuclear-export-inhibition-in-lung-cancer
#4
Arjun Gupta, Jessica M Saltarski, Michael A White, Pier P Scaglioni, David E Gerber
Intracellular compartmentalization and trafficking of molecules plays a critical role in complex and essential cellular processes. In lung cancer and other malignancies, aberrant nucleocytoplasmic transport of tumor suppressor proteins and cell cycle regulators results in tumorigenesis and inactivation of apoptosis. Pharmacologic targeting of this process, termed selective inhibition of nuclear export (SINE), has demonstrated anti-tumor efficacy in preclinical models and human clinical trials. Exportin-1 (XPO1)-which serves as the sole exporter of several tumor suppressor proteins and cell cycle regulators, including retinoblastoma (Rb), adenomatous polyposis coli (APC), p53, p73, p21, p27, FOXO, STAT3, IKB, topoisomerase II and PAR-4-is the principal focus of SINE drug development...
June 21, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28647665/comparative-metabolism-of-ddao-benzoate-in-liver-microsomes-from-various-species
#5
Hong-Ying Ma, Jia-Da Yang, Jie Hou, Li-Wei Zou, Qiang Jin, Da-Cheng Hao, Jing Ning, Guang-Bo Ge, Ling Yang
DDAB (6,8-dichloro-9,9-dimethyl-7-oxo-7,9-dihydroacridin-2-yl benzoate) is a newly developed near-infrared fluorescent probe for human carboxylesterase 2 (hCE2), exhibiting high specificity and good reactivity for real-time monitoring the enzymatic activities of hCE2 in complex biological systems. In order to explore the applicability of DDAB in commonly used animal species, the interspecies difference in DDAB hydrolysis was carefully investigated by using liver microsomes from human and five experimental animals including mouse, rat, dog, minipig and monkey...
June 21, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28647590/differences-in-the-coronal-proteome-acquired-by-particles-depositing-in-the-lungs-of-asthmatic-versus-healthy-humans
#6
Abhinav Kumar, Elif Melis Bicer, Paul Pfeffer, Marco P Monopoli, Kenneth A Dawson, Jonny Eriksson, Katarina Edwards, Steven Lynham, Matthew Arno, Annelie F Behndig, Anders Blomberg, Graham Somers, Dave Hassall, Lea Ann Dailey, Ben Forbes, Ian Mudway
Most inhaled nanomedicines in development are for the treatment of lung disease, yet little is known about their interaction with the respiratory tract lining fluids (RTLF). Here we combined the use of nano-silica, as a protein concentrator, with label-free snapshot proteomics (LC-MS/MS; key findings confirmed by ELISA) to generate a quantitative profile of the RTLF proteome and provided insight into the evolved corona; information that may be used in future to improve drug targeting to the lungs by inhaled medicines...
June 21, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28647589/mannose-conjugated-layered-double-hydroxide-nanocomposite-for-targeted-sirna-delivery-to-enhanced-cancer-therapy
#7
Li Li, Run Zhang, Wenyi Gu, Zhi Ping Xu
Sheet-like layered double hydroxide nanoparticles (LDH NPs) have showed great potentials in biomedical applications such as nanocarriers for drug and gene delivery, biosensors and imaging agents. However, target delivery of drugs and genes using LDH NPs to the desired tumor sites is a major challenge in cancer therapy. The aim of this study is to develop a functional LDH-based nanocomposite for target delivery of siRNA to cancer cells. Mannose as a targeting moiety was firstly conjugated onto SiO2-coated LDH nanocomposite...
June 21, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28647567/stearoyl-coa-desaturase-regulates-sorafenib-resistance-via-modulation-of-er-stress-induced-differentiation
#8
Mark Kin Fai Ma, Eunice Yuen Ting Lau, Doris Hoi Wing Leung, Jessica Lo, Nicole Pui Yu Ho, Lily Kwan Wai Cheng, Stephanie Ma, Chi Ho Lin, John A Copland, Jin Ding, Regina Cheuk Lam Lo, Irene Oi Lin Ng, Terence Kin Wah Lee
We investigated the functional role and clinical significance of Stearoyl CoA desaturase-1 (SCD1) mediated endoplasmic reticulum (ER) stress in regulation of liver tumor-initiating cells (T-ICs) and sorafenib resistance, aiming to develop a novel therapeutic strategy against hepatocellular carcinomas (HCCs) METHODS We evaluated the clinic-pathological relevance of SCD1 and its correlation with sorafenib resistance in large cohorts of HCC clinical samples by qPCR and immunohistochemical analyses. Lentiviral-based overexpression and knockdown approaches were performed to characterize functional roles of SCD1 in regulation of liver T-ICs and sorafenib resistance...
June 21, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28647539/chemical-addressability-of-potato-virus-x-for-its-applications-in-bio-nanotechnology
#9
Duc H T Le, He Hu, Ulrich Commandeur, Nicole F Steinmetz
Potato virus X (PVX), a type member of the plant virus potexvirus group, offers a unique nanotechnology platform based on its high aspect ratio, flexible filamentous shape. The PVX platform has already been engineered and studied for its uses in imaging, drug delivery, and immunotherapies. While genetic engineering procedures are well established for PVX, there is limited information about chemical conjugation strategies for functionalizing PVX, partly due to the lack of structural information of PVX at high resolution...
June 21, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/28647517/proteomics-to-study-macrophage-response-to-viral-infection
#10
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/28647441/prevention-of-epilepsy-should-we-be-avoiding-clinical-trials
#11
REVIEW
Pavel Klein, Ivana Tyrlikova
Epilepsy prevention is one of the great unmet needs in epilepsy. Approximately 15% of all epilepsy is caused by an acute acquired CNS insult such as traumatic brain injury (TBI), stroke or encephalitis. There is a latent period between the insult and epilepsy onset that presents an opportunity to intervene with preventive treatment that is unique in neurology. Yet no phase 3 epilepsy prevention studies, and only 2 phase 2 studies have been initiated in the last 16years. Current prevailing opinion is that the research community is not ready for clinical preventive epilepsy studies, and that animal models should first be refined and biomarkers of epileptogenesis and of epilepsy discovered before clinical studies are embarked upon...
June 21, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28647378/leishmaniasis-drug-discovery-recent-progress-and-challenges-in-assay-development
#12
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/28647364/crystal-structures-of-the-isochorismatase-domains-from-vibrio-anguillarum
#13
Jiansen Du, Tian Deng, Qingjun Ma
Antibiotic resistance is becoming a global threat and overuse of antibiotics in aquaculture disease control worsens the situation. To reduce the risk of drug resistance developed in aquaculture, safer biocontrol programs are needed. Antivirulence therapy, with less chance for developing drug resistance, is a promising approach. To facilitate antivirulence inhibitor design against Vibrio anguillarum, a serious aquaculture pathogen, we present crystal structures for isochorismatase domains of AngB and VabB, which are required to synthesize siderophore, a critical virulence factor...
June 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28647277/risk-factors-for-nosocomial-infections-in-patients-receiving-extracorporeal-membrane-oxygenation-supportive-therapy
#14
Geqin Sun, Binfei Li, Haili Lan, Juan Wang, Lanfei Lu, Xueqin Feng, Xihua Luo, Haizhong Yan, Yuejing Mu
BACKGROUND AND OBJECTIVE: The aim of this study was to analyze risk factors for nosocomial infection (NI) in patients receiving extracorporeal membrane oxygenation (ECMO) support. PATIENTS AND METHODS: Clinical NI data were collected from patients who received ECMO support therapy, and analyzed retrospectively. RESULTS: Among 75 ECMO patients, 20 were found to have developed NI (infection rate 26.7%); a total of 58 pathogens were isolated, including 43 strains of gram-negative bacteria (74...
June 21, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28647214/development-and-in-vivo-evaluation-of-functionalized-ritonavir-proliposomes-for-lymphatic-targeting
#15
Vasif Ahammed, Reema Narayan, John Paul, Yogendra Nayak, Bisakha Roy, Gopal V Shavi, Usha Y Nayak
AIMS: The aim of the present work was to prepare, characterize, and evaluate proliposomes containing lipophilic prodrug ritonavir for targeting towards CD4+ T cells in the lymphatic system. MATERIALS AND METHODS: The liposomes were prepared by lipid thin film hydration method and lyophilized in the presence of cryoprotectant mannitol to obtain proliposomes. The optimized proliposomes by Central Composite Design, were surface modified with biotin. The proliposomes were evaluated for particle size, zeta potential, polydispersity index (PDI), entrapment efficiency, in vitro drug release, in vivo pharmacokinetics and biodistribution studies...
June 21, 2017: Life Sciences
https://www.readbyqxmd.com/read/28647094/long-term-prognosis-of-hematogenous-vertebral-osteomyelitis-mortality-quality-of-life-and-pain
#16
Terufumi Kokabu, Masahiko Takahata, Nobuhisa Ishiguro, Norimasa Iwasaki
BACKGROUND: Hematogenous vertebral osteomyelitis (HVO) has a generally favorable prognosis if appropriate treatment is initiated in its early phase; however, some intractable cases with HVO can develop neurological impairment as well as spinal deformity during the course of treatment and these sequelae may lead to impaired quality of life (QOL). In this study, we aimed to evaluate the long-term relapse rate, mortality, and QOL of patients with HVO. METHODS: In this retrospective case series study, medical records of 60 patients with HVO with a mean follow-up period of 8 years (5-23 years) were reviewed to assess demographic data, details of infection, and clinical course...
June 21, 2017: Journal of Orthopaedic Science: Official Journal of the Japanese Orthopaedic Association
https://www.readbyqxmd.com/read/28647089/reverse-phase-protein-arrays-elucidate-mechanisms-of-action-and-phenotypic-response-in-2d-and-3d-models
#17
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/28647086/phenotypic-chemical-biology-for-predicting-safety-and-efficacy
#18
REVIEW
Ellen L Berg
Phenotypic assays using in vitro cell cultures to forecast compound effects in people are transforming pharmaceutical research and contribute to alternative methods for chemical safety testing. How these assays are validated for human disease relevance is a critical factor for developing more predictive assays. Chemical biology, using drugs as well as target-selective chemical probes, is a direct and efficient approach for establishing disease relevance. Chemical probes can connect information across assays and associate targets to clinical effects...
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
#19
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
#20
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
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