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https://www.readbyqxmd.com/read/28432573/clinical-outcomes-in-trials-evaluating-lipid-lowering-drugs
#1
REVIEW
Julie Butters, Alex Brown, Liddy Griffith, Susan Kim, Stephen J Nicholls
While statins have formed the cornerstone of strategies for cardiovascular prevention, the residual risk related to low-density lipoprotein cholesterol (LDL-C) and other lipoprotein factors provides a landscape for development of new therapies. However, a number of lipid-modifying therapies have failed to reduce cardiovascular event rates in contemporary clinical trials of statin-treated patients. The factors considered in outcome measure selection for clinical trials of novel lipid-lowering therapies are reviewed...
April 21, 2017: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
https://www.readbyqxmd.com/read/28432048/solithromycin-a-novel-ketolide-antibiotic
#2
Michael J Buege, Jack E Brown, Samuel L Aitken
PURPOSE: The pharmacology, pharmacokinetics, pharmacodynamics, antimicrobial activity, clinical safety, and current regulatory status of solithromycin are reviewed. SUMMARY: Solithromycin is a novel ketolide antibiotic developed for the treatment of community-acquired bacterial pneumonia (CABP). Its pharmacologic, pharmacokinetic, and pharmacodynamic properties provide activity against a broad range of intracellular organisms, including retained activity against pathogens displaying various mechanisms of macrolide resistance...
April 21, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28432031/membrane-lipid-replacement-for-chronic-illnesses-aging-and-cancer-using-oral-glycerolphospholipid-formulations-with-fructooligosaccharides-to-restore-phospholipid-function-in-cellular-membranes-organelles-cells-and-tissues
#3
REVIEW
Garth L Nicolson, Michael E Ash
Membrane Lipid Replacement is the use of functional, oral supplements containing mixtures of cell membrane glycerolphospholipids, plus fructooligosaccharides (for protection against oxidative, bile acid and enzymatic damage) and antioxidants, in order to safely replace damaged, oxidized, membrane phospholipids and restore membrane, organelle, cellular and organ function. Defects in cellular and intracellular membranes are characteristic of all chronic medical conditions, including cancer, and normal processes, such as aging...
April 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28431671/where-are-we-now-a-clinicians-guide-to-the-use-of-follow-on-insulin-for-patients-with-diabetes
#4
Steven V Edelman, Priscilla A Hollander, Eugene E Wright
Insulin has been used as a standard treatment for patients with diabetes for almost 100 years. Over time, advances in insulin development have improved its pharmacologic properties. (Online access: http://courses.elseviercme.com/t2dm/666). Most recently, the US Food and Drug Administration approved a novel, follow-on basal insulin agent, with more expected to be commercially available in the near future. With the imminent availability of follow-on basal insulin agents, clinicians need to be aware of the potential benefits and concerns in order to facilitate informed decision making and to provide the best possible advice and guidance to their patients with diabetes...
May 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28430919/non-coding-rnas-in-cardiovascular-diseases-diagnostic-and-therapeutic-perspectives
#5
Wolfgang Poller, Stefanie Dimmeler, Stephane Heymans, Tanja Zeller, Jan Haas, Mahir Karakas, David-Manuel Leistner, Philipp Jakob, Shinichi Nakagawa, Stefan Blankenberg, Stefan Engelhardt, Thomas Thum, Christian Weber, Benjamin Meder, Roger Hajjar, Ulf Landmesser
Recent research has demonstrated that the non-coding genome plays a key role in genetic programming and gene regulation during development as well as in health and cardiovascular disease. About 99% of the human genome do not encode proteins, but are transcriptionally active representing a broad spectrum of non-coding RNAs (ncRNAs) with important regulatory and structural functions. Non-coding RNAs have been identified as critical novel regulators of cardiovascular risk factors and cell functions and are thus important candidates to improve diagnostics and prognosis assessment...
April 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28430857/repurposed-drugs-targeting-eif2%C3%AE-p-mediated-translational-repression-prevent-neurodegeneration-in-mice
#6
Mark Halliday, Helois Radford, Karlijn A M Zents, Collin Molloy, Julie A Moreno, Nicholas C Verity, Ewan Smith, Catharine A Ortori, David A Barrett, Martin Bushell, Giovanna R Mallucci
Signalling through the PERK/eIF2α-P branch of the unfolded protein response plays a critical role in controlling protein synthesis rates in cells. This pathway is overactivated in brains of patients with Alzheimer's disease and related disorders and has recently emerged as a promising therapeutic target for these currently untreatable conditions. Thus, in mouse models of neurodegenerative disease, prolonged overactivation of PERK/eIF2α-P signalling causes sustained attenuation of protein synthesis, leading to memory impairment and neuronal loss...
April 19, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28429653/clinical-development-of-fenretinide-as-an-antineoplastic-drug-pharmacology-perspectives
#7
Jason P Cooper, C Patrick Reynolds, Hwangeui Cho, Min H Kang
Fenretinide (4-HPR) is a synthetic retinoid that has cytotoxic activity against cancer cells. Despite substantial in vitro cytotoxicity, response rates in early clinical trials with 4-HPR have been less than anticipated, likely due to the low bioavailability of the initial oral capsule formulation. Several clinical studies have shown that the oral capsule formulation at maximum tolerated dose (MTD) achieved <10 µmol/L concentrations in patients. To improve bioavailability of 4-HPR, new oral powder (LYM-X-SORB®, LXS) and intravenous lipid emulsion (ILE) formulations are being tested in early-phase clinical trials...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28428753/a-clinical-perspective-of-anti-fibrotic-therapies-for-cardiovascular-disease
#8
REVIEW
Lu Fang, Andrew J Murphy, Anthony M Dart
Cardiac fibrosis are central to various cardiovascular diseases. Research on the mechanisms and therapeutic targets for cardiac fibrosis has advanced greatly in recent years. However, while many anti-fibrotic treatments have been studied in animal models and seem promising, translation of experimental findings into human patients has been rather limited. Thus, several potential new treatments which have shown to reduce cardiac fibrosis in animal models have either not been tested in humans or proved to be disappointing in clinical trials...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28427321/in-silico-assessment-of-biomedical-products-the-conundrum-of-rare-but-not-so-rare-events-in-two-case-studies
#9
Marco Viceconti, Claudio Cobelli, Tarek Haddad, Adam Himes, Boris Kovatchev, Mark Palmer
In silico clinical trials, defined as "The use of individualized computer simulation in the development or regulatory evaluation of a medicinal product, medical device, or medical intervention," have been proposed as a possible strategy to reduce the regulatory costs of innovation and the time to market for biomedical products. We review some of the the literature on this topic, focusing in particular on those applications where the current practice is recognized as inadequate, as for example, the detection of unexpected severe adverse events too rare to be detected in a clinical trial, but still likely enough to be of concern...
May 2017: Proceedings of the Institution of Mechanical Engineers. Part H, Journal of Engineering in Medicine
https://www.readbyqxmd.com/read/28426554/barking-up-the-right-tree-advancing-our-understanding-and-treatment-of-lymphoma-with-a-spontaneous-canine-model
#10
Dania Villarnovo, Angela L McCleary-Wheeler, Kristy L Richards
PURPOSE OF REVIEW: Spontaneous lymphoma in pet dogs is increasingly recognized as an ideal model for studying the disease in humans and for developing new targeted therapeutics for patients. Increasing interest by funding agencies, the private sector, and multidisciplinary academic collaborations between different disciplines and sectors now enables large knowledge gaps to be addressed and provides additional proof-of-concept examples to showcase the significance of the canine model. RECENT FINDINGS: The current review addresses the rationale for a canine lymphoma model including the valuable role it can play in drug development, serving as a link between mouse xenograft models and human clinical trials and the infrastructure that is now in place to facilitate these studies...
April 19, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28426519/toward-a-universal-antiretroviral-regimen-special-considerations-of-pregnancy-and-breast-feeding
#11
Amy L Slogrove, Polly Clayden, Elaine J Abrams
PURPOSE OF REVIEW: As optimized antiretroviral therapy (ART) regimens are prepared for introduction in low-income and middle-income countries (LMIC), we consider the current evidence related to dosing, efficacy and safety during pregnancy and breastfeeding of next-generation first-line and second-line ART regimens proposed for imminent introduction in the global marketplace. RECENT FINDINGS: Pregnancy pharmacokinetic considerations include potentially insufficient efavirenz exposure if dosed at 400 mg/day, the need for twice daily darunavir dosing and the paucity of data related to tenofovir alafenamide and dolutegravir dosing, safety and efficacy...
April 19, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28424564/new-developments-in-the-management-of-narcolepsy
#12
REVIEW
Vivien C Abad, Christian Guilleminault
Narcolepsy is a life-long, underrecognized sleep disorder that affects 0.02%-0.18% of the US and Western European populations. Genetic predisposition is suspected because of narcolepsy's strong association with HLA DQB1*06-02, and genome-wide association studies have identified polymorphisms in T-cell receptor loci. Narcolepsy pathophysiology is linked to loss of signaling by hypocretin-producing neurons; an autoimmune etiology possibly triggered by some environmental agent may precipitate hypocretin neuronal loss...
2017: Nature and Science of Sleep
https://www.readbyqxmd.com/read/28424538/metal-complexes-in-cancer-therapy-an-update-from-drug-design-perspective
#13
REVIEW
Umar Ndagi, Ndumiso Mhlongo, Mahmoud E Soliman
In the past, metal-based compounds were widely used in the treatment of disease conditions, but the lack of clear distinction between the therapeutic and toxic doses was a major challenge. With the discovery of cisplatin by Barnett Rosenberg in 1960, a milestone in the history of metal-based compounds used in the treatment of cancers was witnessed. This forms the foundation for the modern era of the metal-based anticancer drugs. Platinum drugs, such as cisplatin, carboplatin and oxaliplatin, are the mainstay of the metal-based compounds in the treatment of cancer, but the delay in the therapeutic accomplishment of other metal-based compounds hampered the progress of research in this field...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28424071/imatinib-treatment-of-poor-prognosis-mesenchymal-type-primary-colon-cancer-a-proof-of-concept-study-in-the-preoperative-window-period-impacct
#14
I Ubink, H J Bloemendal, S G Elias, M A Brink, M P Schwartz, Y C W Holierhoek, P M Verheijen, A W Boerman, R H J Mathijssen, W W J de Leng, R A de Weger, W M U van Grevenstein, M Koopman, M P Lolkema, O Kranenburg, I H M Borel Rinkes
BACKGROUND: The identification of four Consensus Molecular Subtypes (CMS1-4) of colorectal cancer forms a new paradigm for the design and evaluation of subtype-directed therapeutic strategies. The most aggressive subtype - CMS4 - has the highest chance of disease recurrence. Novel adjuvant therapies for patients with CMS4 tumours are therefore urgently needed. CMS4 tumours are characterized by expression of mesenchymal and stem-like genes. Previous pre-clinical work has shown that targeting Platelet-Derived Growth Factor Receptors (PDGFRs) and the related KIT receptor with imatinib is potentially effective against mesenchymal-type colon cancer...
April 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28423702/experience-with-precision-genomics-and-tumor-board-indicates-frequent-target-identification-but-barriers-to-delivery
#15
Alan H Bryce, Jan B Egan, Mitesh J Borad, A Keith Stewart, Grzegorz S Nowakowski, Asher Chanan-Khan, Mrinal M Patnaik, Stephen M Ansell, Michaela S Banck, Steven I Robinson, Aaron S Mansfield, Eric W Klee, Gavin R Oliver, Jennifer B McCormick, Norine E Huneke, Colleen M Tagtow, Robert B Jenkins, Kandelaria M Rumilla, Sarah E Kerr, Jean-Pierre A Kocher, Scott A Beck, Martin E Fernandez-Zapico, Gianrico Farrugia, Konstantinos N Lazaridis, Robert R McWilliams
BACKGROUND: The ability to analyze the genomics of malignancies has opened up new possibilities for off-label targeted therapy in cancers that are refractory to standard therapy. At Mayo Clinic these efforts are organized through the Center for Individualized Medicine (CIM). RESULTS: Prior to GTB, datasets were analyzed and integrated by a team of bioinformaticians and cancer biologists. Therapeutically actionable mutations were identified in 65% (92/141) of the patients tested with 32% (29/92) receiving genomically targeted therapy with FDA approved drugs or in an independent clinical trial with 45% (13/29) responding...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423651/succinate-dehydrogenase-b-deficient-cancer-cells-are-highly-sensitive-to-bromodomain-and-extra-terminal-inhibitors
#16
Satoshi Kitazawa, Shunsuke Ebara, Ayumi Ando, Yuji Baba, Yoshinori Satomi, Tomoyoshi Soga, Takahito Hara
Mutations in succinate dehydrogenase B (SDHB) gene are frequently observed in several tumors and associated with poor prognosis in these tumors. Therefore, drugs effective for SDHB-deficient tumors could fulfill an unmet medical need. In addition, such drugs would have an advantage in that selection of patients with SDHB-mutant cancer could increase the probability of success in clinical trials. Currently, however, the characteristics of SDHB-deficient cancers are not completely understood. Here, we established SDHB knockout cancer cell lines from human colon cancer HCT116 cells using the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 knockout system, and clarified its metabolic characteristics...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419972/neprilysin-inhibitors-a-new-hope-to-halt-the-diabetic-cardiovascular-and-renal-complications
#17
REVIEW
Vajir Malek, Anil Bhanudas Gaikwad
Diabetes is an enormous and ever-growing calamity and a global public health threat of the 21st century. Besides insulin and oral hypoglycaemic drugs, blockage of the renin-angiotensin system (RAS) denotes a key pharmacotherapy for the management of cardiovascular (CVD) and chronic kidney diseases (CKD), which are the leading causes of disability and death among diabetic patients. Neprilysin (NEP) inhibition, auxiliary to RAS blockage increases the bioavailability of natriuretic peptides and benefits the cardio-renal system...
April 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28419657/a-new-approach-to-clinical-research-integrating-clinical-care-quality-reporting-and-research-using-a-wound-care-network-based-learning-healthcare-system
#18
Thomas E Serena, Caroline E Fife, Kristen A Eckert, Raphael A Yaakov, Marissa J Carter
The disparity between ideal evidence from randomized controlled trials and real-world evidence in medical research has prompted the United States Food and Drug Administration to consider the use of real-world data to better understand safety and effectiveness of new devices for a broader patient population and to prioritize real-world data in regulatory decision making. As the healthcare system transitions from volume- to value-based care, there is a growing need to harness the power of real-world data to change the paradigm for wound care clinical research and enable more generalizable clinical trials...
April 17, 2017: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/28419192/efficacy-and-safety-of-a-novel-acetylcholinesterase-inhibitor-octohydroaminoacridine-in-mild-to-moderate-alzheimer-s-disease-a-phase-ii-multicenter-randomised-controlled-trial
#19
Shifu Xiao, Tao Wang, Xiuqiang Ma, Yingyi Qin, Xia Li, Zhongxin Zhao, Xueyuan Liu, Xiaoping Wang, Hengge Xie, Qinpu Jiang, Li Sun, Benyan Luo, Lan Shang, Weixian Chen, Yan Bai, Muni Tang, Maolin He, Lan Wu, Qilin Ma, Deren Hou, Jia He
Background: inhibition of acetylcholinesterase (AChE) has been a effective treatment for Alzheimer's disease (AD). Octohydroaminoacridine, a new AChE inhibitor, is a potential treatment for AD. Method: we conducted a multicenter, randomised, double blind, placebo-controlled, parallel-group Phase II clinical trial to investigate the effects of octohydroaminoacridine in patients with mild-to-moderate AD. Patients were randomised to receive placebo thrice daily, octohydroaminoacridine 1 mg/thrice daily (TID) (low-dose group), 2 mg/TID (middle-dose group) or 4 mg/TID (high-dose group)...
April 17, 2017: Age and Ageing
https://www.readbyqxmd.com/read/28417858/-18-f-fdg-pet-ct-imaging-of-thoracic-and-extrathoracic-tuberculosis-in-children
#20
REVIEW
Matthieu Pelletier-Galarneau, Patrick Martineau, Lionel S Zuckier, Xuan Pham, Raymond Lambert, Sophie Turpin
Tuberculosis (TB) remains a major health problem, affecting approximately one-third of the world׳s population. The tubercle bacillus can affect virtually any organ of the human body and if left untreated can lead to severe morbidity and death. Diagnosis of active TB is challenging, especially in children. As a "great imitator," the disease can mimic numerous other pathologies, both clinically and at imaging. Although recognition of active TB is crucial to initiate adequate treatment in a timely fashion, thereby preventing transmission of disease, differentiation of active and quiescent disease is not always straightforward...
May 2017: Seminars in Nuclear Medicine
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