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https://www.readbyqxmd.com/read/29779164/update-on-endothelin-receptor-antagonists-in-hypertension
#1
REVIEW
Michel Burnier
To review the most recent data on the development of endothelin receptor antagonists (ERAs) for the treatment of hypertension and the management of diabetic nephropathy RECENT FINDINGS: Recent reviews and meta-analyses of experimental and clinical data obtained with ERAs confirmed that endothelin receptor blockade is associated with significant decreases in blood pressure in essential hypertension but also in resistant hypertension. In addition, in patients with diabetic nephropathy, ERAs induce significant 30-40% decreases in albuminuria when administered on top of blockers of the renin-angiotensin system...
May 19, 2018: Current Hypertension Reports
https://www.readbyqxmd.com/read/29778846/efficacy-and-tolerability-of-treatment-with-lacosamide-postmarketing-experience-from-the-middle-east-region
#2
Maher Arabi, Taoufik Alsaadi, Wassim Nasreddine, Jasem Al-Hashel, Maya Dirani, Ahmad Beydoun
PURPOSE: Lacosamide (LCM) was recently introduced in the Middle East. The aim of this study was to evaluate the safety, tolerability, and efficacy of LCM in patients with focal onset seizures and determine if our results are comparable with those derived from Western countries. METHODS: This is a retrospective analysis from two medical centers on consecutive patients diagnosed as having focal onset seizures and treated with add-on LCM. The primary efficacy variables were the 50% responder and seizure-free rates, and the secondary outcome variables included the percentages of patients who achieved seizure remission during the last 6-month follow-up period and the percentages of discontinuation due to lack of efficacy or tolerability...
May 17, 2018: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29778449/mechanisms-underlying-the-relaxation-by-a484954-a-eukaryotic-elongation-factor-2-kinase-inhibitor-in-rat-isolated-mesenteric-artery
#3
Tomoko Kodama, Muneyoshi Okada, Hideyuki Yamawaki
Eukaryotic elongation factor 2 kinase (eEF2K) is a calmodulin-related protein kinase which regulates protein translation. A484954 is an inhibitor of eEF2K. In the present study, we investigated the acute effects of A484954 on contractility of isolated blood vessels. Isometric contraction of rat isolated aorta and main branch of superior mesenteric artery (MA) was measured. Expression of an inward rectifier K+ (Kir ) channel subtype mRNA and protein was examined. A484954 caused relaxation in endothelium-intact [E (+)] and -denuded [E (-)] aorta or MA precontracted with noradrenaline (NA)...
May 2, 2018: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29778281/role-of-the-water-drinking-test-in-medically-treated-primary-open-angle-glaucoma-patients
#4
H Salcedo, D Arciniega, M Mayorga, L Wu
PURPOSE: The water-drinking test (WDT) has recently re-emerged as a possible way to determine the competency of the trabecular meshwork. We performed a prospective interventional study to test the hypothesis that the WDT could be useful in assessing fluctuations in patients undergoing treatment for primary open angle glaucoma (POAG). METHODS: We included 122 patients; 62 on medical treatment for POAG (n=123 eyes) and 60 controls (n=120 eyes). The study group had been on intraocular pressures (IOP) lowering treatment continuously for at least 3months with stable IOP...
May 16, 2018: Journal Français D'ophtalmologie
https://www.readbyqxmd.com/read/29777848/effects-on-mortality-and-cardiovascular-events-of-adherence-to-guideline-recommended-therapy-4-years-after-lower-extremity-arterial-revascularization
#5
M Thiney, N Della Schiava, R Ecochard, P Feugier, P Lermusiaux, A Millon, A Long
OBJECTIVES: All patients with lower extremity peripheral arterial disease (LE-PAD) should benefit from recommended pharmacologic therapies including antiplatelet agents, angiotensin converting enzyme inhibitors (ACE) or Angiotensin receptor blockers (ARB), and HMG-CoA-reductase inhibitors (statins). In the present study, this triple therapy was defined as the best medical treatment. This study was designed to determine the current risk for cardiovascular (CV) events and mortality and also to evaluate the effect of pharmacologic treatment on patient's survival, CV events and additional vascular surgery in vascularized LE-PAD patients...
May 16, 2018: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/29777285/insufficient-left-ventricular-unloading-after-extracorporeal-membrane-oxygenation-a-case-series-observational-study
#6
W Hu, J Zhou, L Chen, J Huang, W Hu, Y Zhu, T Yuan
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a method widely used to support circulation in patients with fulminant myocarditis (FM). However, a common complication associated with ECMO is left ventricular (LV) overload. METHODS: This case series observed the effects of intra-aortic balloon pump (IABP) and beta-blockers for the treatment of LV overload after ECMO. The cases of eight patients with FM who underwent ECMO from September 2009 to July 2016 were reviewed...
May 18, 2018: Herz
https://www.readbyqxmd.com/read/29777284/current-drug-therapy-for-heart-failure-with-reduced-ejection-fraction
#7
D Berliner, M Hallbaum, J Bauersachs
The prevalence of heart failure has been steadily increasing during the past few years, with a further increase predicted in the years to come. Without treatment, the syndrome of heart failure has a very poor prognosis. Advances in drug treatments and the consequent implementation of a guideline-recommended drug therapy have significantly improved the prognosis in heart failure with reduced ejection fraction (HFrEF). Besides angiotensin-converting enzyme (ACE) inhibitors (ACEi) or angiotensin receptor blockers, beta-blockers and diuretics treatment with mineralocorticoid receptor antagonists and ivabradine have become standard in the therapy of symptomatic patients with HFrEF...
May 18, 2018: Herz
https://www.readbyqxmd.com/read/29775659/%C3%AE-2-receptors-in-the-lateral-parabrachial-nucleus-generates-the-pressor-response-of-the-cardiovascular-chemoreflex-effects-of-gaba-a-receptor
#8
Nafiseh Mirzaei Damabi, Gholam Reza Namvar, Fahimeh Yeganeh, Masoumeh Hatam
The lateral parabrachial nucleus (LPBN) is a pontine area involved in cardiovascular chemoreflex. This study was performed to find the effects of reversible synaptic blockade of the LPBN on the chemoreflex responses, and to find the roles of GABAA receptor and α2 -adenoreceptor (α2 -AR) in chemoreflex. It also aimed to seek possible interaction between GABA and noradrenergic systems of the LPBN in urethane-anesthetized male rats. Cardiovascular chemoreflex was activated by intravenous injection of potassium cyanide (KCN, 80 μg/kg)...
May 15, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29775303/simultaneous-targeting-of-rgd-integrins-and-dual-murine-double-minute-proteins-in-glioblastoma-multiforme
#9
Francesco Merlino, Simona Daniele, Valeria La Pietra, Salvatore Di Maro, Francesco Saverio Di Leva, Diego Brancaccio, Stefano Tomassi, Stefano Giuntini, Linda Cerofolini, Marco Fragai, Claudio Luchinat, Florian Reichart, Chiara Cavallini, Barbara Costa, Rebecca Piccarducci, Sabrina Taliani, Federico Da Settimo, Claudia Martini, Horst Kessler, Ettore Novellino, Luciana Marinelli
In the fight against Glioblastoma Multiforme, recent literature data have highlighted that integrin α5β1 and p53 are part of convergent pathways in the control of glioma apoptosis. This observation prompted us to seek a molecule able to simultaneously modulate both target families. Analyzing the results of a previous virtual screening against murine double minute 2 protein (MDM2), we envisaged that Arg-Gly-Asp (RGD)-mimetic molecules could be inhibitors of MDM2/4. Herein we present the discovery of compound 7, which inhibits both MDM2/4 and α5β1/αvβ3 integrins...
May 18, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29774881/-effect-of-down-regulation-of-iks-repolarization-reserve-on-ventricular-arrhythmogenesis-in-a-guinea-pig-model-of-cardiac-hypertrophy
#10
Hegui Wang, Ting Huang, Zheng Wang, Nannan Ge, Yongsheng Ke
To observe the changes of rapidly activated delayed rectifier potassium channel (IKr) and slowly activated delayed rectifier potassium channel (IKs) in cardiac hypertrophy and to evaluate the effects of IKr and IKs blocker on the incidence of ventricular arrhythmias in guinea pigs with left ventricular hypertrophy (LVH).
 Methods: Guinea pigs were divided into a sham operation group and a left ventricular hypertrophy (LVH) group. LVH model was prepared. Whole cell patch-clamp technique was used to record IKr and IKs tail currents in a guinea pig model with LVH...
April 28, 2018: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29774464/eculizumab-in-stec-hus-need-for-a-proper-randomized-controlled-trial
#11
Sebastian Loos, Jun Oh, Markus J Kemper
Hemolytic uremic syndrome caused by Shiga toxin-producing E. coli (STEC-HUS) is often associated with a severe morbidity including neurological involvement and a mortality of 1-5%. Although STEC-HUS is often self-limited, improvement of treatment strategies is needed for cases with complications and, among others, plasma exchange/plasmapheresis and use of antibiotics have been advocated. With the availability of the complement blocker eculizumab, now a standard treatment of atypical HUS, several series have addressed its use in STEC-HUS, with variable response; randomized controlled trials are lacking...
May 17, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29774407/beta-blockers-and-chronic-heart-failure-patients-prognostic-impact-of-a-dose-targeted-beta-blocker-therapy-vs-heart-rate-targeted-strategy
#12
Anna Corletto, Hanna Fröhlich, Tobias Täger, Matthias Hochadel, Ralf Zahn, Caroline Kilkowski, Ralph Winkler, Jochen Senges, Hugo A Katus, Lutz Frankenstein
BACKGROUND: Beta blockers improve survival in patients with chronic systolic heart failure (CHF). Whether physicians should aim for target dose, target heart rate (HR), or both is still under debate. METHODS AND RESULTS: We identified 1,669 patients with systolic CHF due to ischemic heart disease or idiopathic dilated cardiomyopathy from the University Hospital Heidelberg and the Clinic of Ludwigshafen, Germany. All patients were treated with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker and had a history of CHF known for at least 6 months...
May 17, 2018: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://www.readbyqxmd.com/read/29774303/myotonia-permanens-with-nav1-4-g1306e-displays-varied-phenotypes-during-course-of-life
#13
Frank Lehmann-Horn, Adele D'Amico, Enrico Bertini, Mauro Lomonaco, Luciano Merlini, Kevin R Nelson, Heike Philippi, Gabriele Siciliano, Frank Spaans, Karin Jurkat-Rott
Introduction: Myotonia permanens due to Nav1.4-G1306E is a rare sodium channelopathy with potentially life-threatening respiratory complications. Our goal was to study phenotypic variability throughout life. Methods: Clinical neurophysiology and genetic analysis were performed. Using existing functional expression data we determined the sodium window by integration. Results: In 10 unrelated patients who were believed to have epilepsy, respiratory disease or Schwartz-Jampel syndrome, we made the same prima facie diagnosis and detected the same heterologous Nav1...
September 2017: Acta Myologica: Myopathies and Cardiomyopathies: Official Journal of the Mediterranean Society of Myology
https://www.readbyqxmd.com/read/29773910/the-l-type-calcium-channel-blocker-isradipine-attenuates-cue-induced-cocaine-seeking-by-enhancing-dopaminergic-activity-in-the-ventral-tegmental-area-to-nucleus-accumbens-pathway
#14
Nii A Addy, Eric J Nunes, Shannon M Hughley, Keri M Small, Sarah J Baracz, Joshua L Haight, Anjali M Rajadhyaksha
Previous preclinical and clinical investigations have focused on the L-type calcium channel (LTCC) as a potential therapeutic target for substance abuse. While some clinical studies have examined the ability of LTCC blockers to alter cocaine's subjective effects, very few LTCC studies have examined cocaine relapse. Here, we examined whether ventral tegmental area (VTA)-specific or systemic administration of the LTCC inhibitor, isradipine, altered cocaine-seeking behavior in a rat model. Male Sprague-Dawley rats first received 10 days of cocaine self-administration training (2 h sessions), where active lever depression resulted in delivery of a ∼0...
May 3, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29773754/a-critical-neurodevelopmental-role-for-l-type-voltage-gated-calcium-channels-in-neurite-extension-and-radial-migration
#15
Satoshi Kamijo, Yuichiro Ishii, Shin-Ichiro Horigane, Kanzo Suzuki, Masamichi Ohkura, Junichi Nakai, Hajime Fujii, Sayaka Takemoto-Kimura, Haruhiko Bito
In spite of many association studies linking gene polymorphisms and mutations of L-type Voltage-Gated Ca2+ Channels (VGCC) in neurodevelopmental disorders, such as autism and schizophrenia, specific L-type VGCC roles during brain development remain unclear. Yet, calcium signaling has been shown to be essential for neurodevelopmental processes such as sculpting of neurites, functional wiring and fine tuning of growing networks. To bridge this gap, we performed submembraneous calcium imaging using a membrane-tethered genetically-encoded calcium indicator (GECI) Lck-G-CaMP7...
May 17, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29773231/biologics-in-sapho-syndrome-a-systematic-review
#16
REVIEW
Dimitrios Daoussis, Georgia Konstantopoulou, Pantelis Kraniotis, Lazaros Sakkas, Stamatis-Nick Liossis
BACKGROUND: The SAPHO syndrome is a relatively rare clinical entity characterized by a wide range of dermatological and musculoskeletal manifestations. Biologics have been used in cases refractory to conventional treatment. METHODS: We present herein a patient with refractory to treatment SAPHO syndrome who exhibited a dramatic and fast response to IL-17 blockade. Additionally, we performed a systematic review of all cases of patients with SAPHO syndrome treated with biologics to date...
April 17, 2018: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/29773156/beta-blockers-for-primary-prevention-of-anthracycline-cardiotoxicity-not-quite-ready-for-prime-time
#17
EDITORIAL
Aarti Asnani
No abstract text is available yet for this article.
May 22, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29772901/the-catch-22-of-predicting-herg-blockade-using-publicly-accessible-bioactivity-data
#18
Vishal Babu Siramshetty, Qiaofeng Chen, Prashanth Devarakonda, Robert Preissner
Drug-induced inhibition of the human Ether-à-go-go-Related Gene (hERG) encoded potassium ion (K+) channels can lead to fatal cardiotoxicity. Several marketed drugs and promising drug candidates were recalled due to this concern. Diverse modeling methods ranging from molecular similarity assessment to quantitative structure activity relationship analysis employing machine learning techniques have been applied to datasets of varying size and composition (number of blockers and non-blockers). In this study, we highlight the challenges involved in development of a robust classifier for predicting the hERG endpoint using bioactivity data extracted from the public domain...
May 17, 2018: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29772211/synthesis-folding-structure-and-activity-of-a-predicted-peptide-from-the-sea-anemone-oulactis-sp-with-an-shkt-fold
#19
Bankala Krishnarjuna, Jessica Villegas-Moreno, Michela L Mitchell, Agota Csoti, Steve Peigneur, Carlos Amero, Michael W Pennington, Jan Tytgat, Gyorgy Panyi, Raymond S Norton
Sea anemone venom is rich in bioactive compounds, including peptides containing multiple disulfide bridges. In a transcriptomic study on Oulactis sp., we identified the putative 36-residue peptide, OspTx2b, which is an isoform of the KV channel blocker OspTx2a (Sunanda P et al. (2018) Identification, chemical synthesis, structure and function of a new KV 1 channel blocking peptide from Oulactis sp. Peptide Science, in press). As OspTx2b contains a ShK/BgK-like cysteine framework, with high amino acid sequence similarity to BgK, we were interested to investigate its structure and function...
May 14, 2018: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29771735/re-beta-blockers-and-improved-progression-free-survival-in-patients-with-advanced-her2-negative-breast-cancer
#20
Gitte Vrelits Sørensen, Deirdre P Cronin-Fenton, Henrik Toft Sørensen, Per Damkier, Bent Ejlertsen, Peer M Christiansen, Timothy L Lash, Thomas P Ahern
No abstract text is available yet for this article.
May 16, 2018: Epidemiology
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