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https://www.readbyqxmd.com/read/28528469/multiple-sclerosis-treatment-with-fingolimod-profile-of-non-cardiologic-adverse-events
#1
REVIEW
Yara Dadalti Fragoso
Fingolimod was the first oral medication approved for management of multiple sclerosis and is currently used by tens of thousands patients worldwide. Fingolimod acts via the sphingosine 1-phosphate (S1P) receptor, maintaining peripheral lymphocytes entrapped in the lymph nodes. In consequence, there is a reduction in the infiltration of aggressive lymphocytes into the central nervous system. The drug is safe and effective, and its first hours of use are associated with related to S1P receptors in the heart...
May 20, 2017: Acta Neurologica Belgica
https://www.readbyqxmd.com/read/28528366/cdk5-mediated-phosphorylation-dependent-ubiquitination-and-degradation-of-e3-ubiquitin-ligases-gp78-accelerates-neuronal-death-in-parkinson-s-disease
#2
Qingzhi Wang, Fengjuan Jiao, Pei Zhang, Jianguo Yan, Zheng Zhang, Feng He, Qian Zhang, Zexi Lv, Xiang Peng, Hongwei Cai, Bo Tian
The molecular mechanisms responsible for the loss of dopaminergic neurons in Parkinson's disease (PD) remain obscure. Loss of function of E3 ubiquitin ligases is associated with mitochondria dysfunction, dysfunction of protein degradation, and α-synuclein aggregation, which are major contributors to neurodegeneration in PD. Recent research has thus focused on E3 ubiquitin ligase glycoprotein 78 (GP78); however, the role of GP78 in PD pathogenesis remains unclear. Notably, cyclin-dependent kinase 5 (CDK5) controls multiple cellular events in postmitotic neurons, and CDK5 activity has been implicated in the pathogenesis of PD...
May 20, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28528303/discovery-of-a-potent-dual-alk-and-egfr-t790m-inhibitor
#3
Jaebong Jang, Jung Beom Son, Ciric To, Magda Bahcall, So Young Kim, Seock Yong Kang, Mierzhati Mushajiang, Younho Lee, Pasi A Jänne, Hwan Geun Choi, Nathanael S Gray
The mutational activations of anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) are validated oncogenic events and the targets of approved drugs to treat non-small cell lung cancer (NSCLC). Here we report highly potent dual small molecule inhibitors of both ALK and EGFR, particularly the T790M mutant which confers resistance to first generation EGFR inhibitors. Dual ALK/EGFR inhibitors may provide an efficient approach to prevent resistance that arises as a consequence of clinically reported reciprocal activation mechanisms...
May 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28528236/-management-of-the-bleeding-risk-associated-with-antiplatelet-agents
#4
A-C Martin, S Houssany-Pissot, D Zlotnik, G Taylor, A Godier
Like all antithrombotic drugs, antiplatelet agents expose to a risk of bleeding complications. Clinical research has extensively focused on the efficacy of these drugs to reduce ischemic events. The bleeding risk associated with them was solely considered as an inevitable and acceptable complication. When two new potent P2Y12-receptor inhibitors, prasugrel and ticagrelor, were marketed, the risk of major bleeding increased. These new agents have modified the balance between the absolute risk reduction in ischemic events and the absolute risk increase in bleeding events...
May 17, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28527782/protective-roles-of-bioactive-peptides-during-ischemia-reperfusion-injury-from-bench-to-bedside
#5
REVIEW
Dongdong Wu, Jun Wang, Honggang Wang, Ailing Ji, Yanzhang Li
Ischemia-reperfusion (I/R) is a well-known pathological condition which may lead to disability and mortality. I/R injury remains an unresolved and complicated situation in a number of clinical conditions, such as cardiac arrest with successful reanimation, as well as ischemic events in brain and heart. Peptides have many attractive advantages which make them suitable candidate drugs in treating I/R injury, such as low toxicity and immunogenicity, good solubility property, distinct tissue distribution pattern, and favorable pharmacokinetic profile...
May 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/28527773/prevalence-management-and-long-term-6-year-outcomes-of-atrial%C3%A2-fibrillation-among-patients-receiving-drug-eluting-coronary-stents
#6
Hyo-In Choi, Jung-Min Ahn, Se Hun Kang, Pil Hyung Lee, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park, Duk-Woo Park, Seung-Jung Park
OBJECTIVES: This study sought to investigate the incidence, management, and clinical relevance of atrial fibrillation (AF) during and after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and evaluate outcomes of different antithrombotic strategies. BACKGROUND: Uncertainty exists regarding the optimal antithrombotic strategy in patients with AF who are undergoing PCI with DES. METHODS: Using a consecutive series of 10,027 patients who underwent DES implantation between 2003 and 2011, we evaluated the overall prevalence and clinical impact of AF...
May 11, 2017: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/28527704/anti-madcam-antibody-pf-00547659-for-ulcerative-colitis-turandot-a-phase-2-randomised-double-blind-placebo-controlled-trial
#7
Séverine Vermeire, William J Sandborn, Silvio Danese, Xavier Hébuterne, Bruce A Salzberg, Maria Klopocka, Dino Tarabar, Tomas Vanasek, Miloš Greguš, Paul A Hellstern, Joo Sung Kim, Miles P Sparrow, Kenneth J Gorelick, Michelle Hinz, Alaa Ahmad, Vivek Pradhan, Mina Hassan-Zahraee, Robert Clare, Fabio Cataldi, Walter Reinisch
BACKGROUND: PF-00547659 is a fully human monoclonal antibody that binds to human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) to selectively reduce lymphocyte homing to the intestinal tract. We aimed to assess the efficacy and safety of PF-00547659 in patients with moderate to severe ulcerative colitis. METHODS: This phase 2, randomised, double-blind, placebo-controlled clinical trial recruited patients aged 18-65 years from 105 centres in 21 countries, with a history (≥3 months) of active ulcerative colitis extending more than 15 cm beyond the anal verge (with a total Mayo score ≥6 and a Mayo endoscopic subscore ≥2) who had failed or were intolerant to at least one conventional therapy...
May 17, 2017: Lancet
https://www.readbyqxmd.com/read/28527149/characterisation-of-drug-related-problems-and-associated-factors-at-a-clinical-pharmacist-service-na%C3%A3-ve-hospital-in-northern-sweden
#8
Cecilia Peterson, Maria Gustafsson
BACKGROUND: Polypharmacy and increased sensitivity to side effects cause adverse drug events, drug-drug interactions and medication errors in the elderly. OBJECTIVE: The objective of this study was to investigate the prevalence and type of drug-related problems and associated factors among patients admitted to a clinical pharmacist service-naïve medical ward in an inland hospital in northern Sweden. METHODS: During September-November 2015 and February-April 2016, clinical pharmacists working as part of a ward team on the medical ward conducted 103 medication reviews...
May 19, 2017: Drugs—Real World Outcomes
https://www.readbyqxmd.com/read/28527133/a-phase-ii-study-of-antibody-drug-conjugate-tak-264-mln0264-in-previously-treated-patients-with-advanced-or-metastatic-pancreatic-adenocarcinoma-expressing-guanylyl-cyclase-c
#9
Khaldoun Almhanna, David Wright, Teresa Macarulla Mercade, Jean-Luc Van Laethem, Antonio Cubillo Gracian, Carmen Guillen-Ponce, Jason Faris, Carolina Muriel Lopez, Richard A Hubner, Johanna Bendell, Alain Bols, Jaime Feliu, Naureen Starling, Peter Enzinger, Devalingham Mahalingham, Wells Messersmith, Huyuan Yang, Adedigbo Fasanmade, Hadi Danaee, Thea Kalebic
Background This phase II open-label, multicenter study evaluated the efficacy, safety, and tolerability of TAK-264 in previously treated patients with advanced or metastatic pancreatic adenocarcinoma expressing guanylyl cyclase C (GCC). Methods Patients with advanced or metastatic pancreatic adenocarcinoma expressing GCC (H-score ≥ 10) received TAK-264 1.8 mg/kg on day 1 of a 21-day cycle as a 30-min intravenous infusion for up to 1 year or until disease progression or unacceptable toxicity. The primary objective was overall response rate (ORR [complete response + partial response (PR)])...
May 19, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28527083/shared-mechanisms-of-epilepsy-migraine-and-affective-disorders
#10
Davide Zarcone, Simona Corbetta
Since the nineteenth century several clinical features have been observed in common between migraine and epilepsy (such as episodic attacks, triggering factors, presence of aura, frequent familiarity), but only in recent years researchers have really engaged in finding a common pathogenic mechanism. From studies of disease incidence, we understand how either migraine among patients with epilepsy or epilepsy among migraine patients are more frequent than in the general population. This association may result from a direct causality, by the same environmental risk factors and/or by a common genetic susceptibility...
May 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28526884/combined-use-of-metformin-and-atorvastatin-attenuates-atherosclerosis-in-rabbits-fed-a-high-cholesterol-diet
#11
Fei Luo, Yuan Guo, Gui-Yun Ruan, Jun-Ke Long, Xi-Long Zheng, Qin Xia, Shui-Ping Zhao, Dao-Quan Peng, Zhen-Fei Fang, Xiang-Ping Li
Statins are widely used to reduce cardiovascular risk. Unfortunately, some patients still experience cardiovascular events though prescribed with high-intensity statins. Metformin, an anti-diabetic drug, was reported to possess anti-atherosclerotic effects. Therefore, the experiments were designed to evaluate whether combined use of metformin and atorvastatin can achieve additional benefits. In rabbits fed a high-cholesterol diet, we evaluated the effects of the combination therapy on atherosclerotic plaques, lipid profiles, blood glucose levels, liver and kidney functions...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526719/management-of-treatment-related-adverse-events-with-agents-targeting-the-mapk-pathway-in-patients-with-metastatic-melanoma
#12
Adil Daud, Katy Tsai
Tremendous progress has been made in the clinical landscape of advanced-stage BRAF V600-mutant melanoma treatment over the past 5 years. Targeted therapies that inhibit specific steps of the mitogen-activated protein kinase pathway have been shown to provide significant overall treatment benefit in patients with this difficult-to-treat disease. Combination therapy with BRAF and MEK inhibitors (dabrafenib plus trametinib or vemurafenib plus cobimetinib, respectively) has become standard of care. These agents are administered until disease progression or unacceptable toxicity occurs; thus, some patients may remain on maintenance therapy for an extended period of time, while toxicities may result in early discontinuation in other patients...
May 18, 2017: Oncologist
https://www.readbyqxmd.com/read/28526565/efficacy-of-indefinite-chronic-oral-antimicrobial-suppression-for-prosthetic-joint-infection-in-the-elderly-a-comparative-study
#13
V Prendki, P Sergent, A Barrelet, E Oziol, E Beretti, M Berlioz-Thibal, F Bouchand, F Dauchy, E Forestier, G Gavazzi, C Ronde-Oustau, J Stirnemann, A Dinh
OBJECTIVES: During prosthetic joint infection (PJI), surgical management is sometimes impossible, indefinite chronic oral antimicrobial suppression (ICOAS) may sometimes be the only option. We evaluated the outcome of elderly patients who benefited from ICOAS for a strictly palliative goal METHODS: We performed a national retrospective cohort study in France of patients aged >75years old with PJI, and managed with ICOAS planned for life long from 2009 to 2014, and compared the population with an event versus the population free of event...
May 16, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28526540/sodium-dependent-glucose-transporters-sglt-in-human-ischemic-heart-a-new-potential-pharmacological-target
#14
Alessandra Di Franco, Giulia Cantini, Alessia Tani, Raffaele Coppini, Sandra Zecchi-Orlandini, Laura Raimondi, Michaela Luconi, Edoardo Mannucci
BACKGROUND: Empagliflozin is reported to reduce cardiovascular mortality and the rate of hospitalization for heart failure in type 2 diabetic patients with prior cardiovascular events. The mechanisms underlying the cardiac effects of this sodium/glucose transporter 2 (SGT2) inhibitor have not yet been clarified, though a direct action of the drug on the cardiomyocytes could be hypothesized. The aim of the present study is to assess the relative expression of SGLT2 and SGLT1, the two most relevant members of the SGLT family being potentially responsive to empagliflozin, in normal, ischemic and hypertrophic human hearts...
May 9, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28526536/trastuzumab-emtansine-versus-capecitabine-plus-lapatinib-in-patients-with-previously-treated-her2-positive-advanced-breast-cancer-emilia-a-descriptive-analysis-of-final-overall-survival-results-from-a-randomised-open-label-phase-3-trial
#15
Véronique Diéras, David Miles, Sunil Verma, Mark Pegram, Manfred Welslau, José Baselga, Ian E Krop, Kim Blackwell, Silke Hoersch, Jin Xu, Marjorie Green, Luca Gianni
BACKGROUND: The antibody-drug conjugate trastuzumab emtansine is indicated for the treatment of patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. Approval of this drug was based on progression-free survival and interim overall survival data from the phase 3 EMILIA study. In this report, we present a descriptive analysis of the final overall survival data from that trial. METHODS: EMILIA was a randomised, international, open-label, phase 3 study of men and women aged 18 years or older with HER2-positive unresectable, locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane...
May 16, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28526489/intravitreous-injection-of-aav2-sflt01-in-patients-with-advanced-neovascular-age-related-macular-degeneration-a-phase-1-open-label-trial
#16
Jeffrey S Heier, Saleema Kherani, Shilpa Desai, Pravin Dugel, Shalesh Kaushal, Seng H Cheng, Cheryl Delacono, Annie Purvis, Susan Richards, Annaig Le-Halpere, John Connelly, Samuel C Wadsworth, Rafael Varona, Ronald Buggage, Abraham Scaria, Peter A Campochiaro
BACKGROUND: Long-term intraocular injections of vascular endothelial growth factor (VEGF)-neutralising proteins can preserve central vision in many patients with neovascular age-related macular degeneration. We tested the safety and tolerability of a single intravitreous injection of an AAV2 vector expressing the VEGF-neutralising protein sFLT01 in patients with advanced neovascular age-related macular degeneration. METHODS: This was a phase 1, open-label, dose-escalating study done at four outpatient retina clinics in the USA...
May 16, 2017: Lancet
https://www.readbyqxmd.com/read/28526416/treatment-strategy-for-type-2-diabetes-with-obesity-focus-on-glucagon-like-peptide-1-receptor-agonists
#17
REVIEW
Qiuhe Ji
PURPOSE: The progressive nature of type 2 diabetes mellitus (T2DM) calls for step-wise intensification of therapy for maintaining normal glycemic levels and lowering cardiovascular (CV) risk. Because obesity is a prominent risk factor and comorbidity of T2DM, it further elevates the CV risk in T2DM. Therefore, it is vital to manage weight, obesity, and glycemic parameters for effective T2DM management. Few oral antidiabetic drugs (sulfonylureas and thiazolidinediones) and insulin are not suitable for obese patients with T2DM because these drugs cause weight gain...
May 16, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28526186/cardiovascular-protection-in-the-treatment-of-type-2-diabetes-a-review-of-clinical-trial-results-across-drug-classes
#18
Francesco Paneni, Thomas F Lüscher
Patients with type 2 diabetes (T2DM) have a significantly higher risk of developing cardiovascular disease (CVD)-namely myocardial infarction, heart failure, and stroke. Despite clear advances in the prevention and treatment of CVD, the impact of T2DM on CVD outcome remains high and continues to escalate. Available evidence indicates that the risk of macrovascular complications increases with the severity of hyperglycemia, thus suggesting that the relation between metabolic disturbances and vascular damage is approximately linear...
May 15, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28526181/empa-reg-outcome-the-cardiologist-s-point-of%C3%A2-view
#19
Son V Pham, Robert Chilton
Cardiologists could view empagliflozin as a cardiovascular drug that also has a beneficial effect on reducing hyperglycemia in patients with type 2 diabetes mellitus (T2DM). The effects of empagliflozin in lowering the risk of cardiovascular death and hospitalization for heart failure in T2DM patients with high cardiovascular risk during the recent Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME) trial may be explained principally in terms of changes to cardiovascular physiology; namely, by the potential ability of empagliflozin to reduce cardiac workload and myocardial oxygen consumption by lowering blood pressure, improving aortic compliance, and improving ventricular arterial coupling...
May 15, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28526091/a-pre-therapeutic-coating-for-medical-devices-that-prevents-the-attachment-of-candida-albicans
#20
Diego Vargas-Blanco, Aung Lynn, Jonah Rosch, Rony Noreldin, Anthony Salerni, Christopher Lambert, Reeta P Rao
BACKGROUND: Hospital acquired fungal infections are defined as "never events"-medical errors that should never have happened. Systemic Candida albicans infections results in 30-50% mortality rates. Typically, adhesion to abiotic medical devices and implants initiates such infections. Efficient adhesion initiates formation of aggressive biofilms that are difficult to treat. Therefore, inhibitors of adhesion are important for drug development and likely to have a broad spectrum efficacy against many fungal pathogens...
May 19, 2017: Annals of Clinical Microbiology and Antimicrobials
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