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https://www.readbyqxmd.com/read/29227582/role-of-the-sodium-hydrogen-exchanger-in-mediating-the-renal-effects-of-drugs-commonly-used-in-the-treatment-of-type-2-diabetes
#1
REVIEW
Milton Packer
Diabetes is characterized by an increased activity of the sodium-hydrogen exchanger (NHE) in the glomerulus and renal tubules, which contributes importantly to the development of nephropathy. Despite the established role played by the exchanger in experimental studies, it has not been specifically targeted by those seeking to develop novel pharmacological treatments for diabetes. This review demonstrates that many existing drugs that are commonly prescribed to patients with diabetes act on the NHE1 and NHE3 isoforms in the kidney...
December 11, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29225105/interpretation-of-b-type-natriuretic-peptides-in-the-era-of-angiotensin-receptor-neprilysin-inhibitors
#2
Paulo Bettencourt, Cândida Fonseca, Fátima Franco, Aurora Andrade, Dulce Brito
Assessment of serum levels of natriuretic peptides, especially the amino-terminal portion (NT-proBNP) and the carboxy-terminal portion (BNP) of pro-B-type natriuretic peptide, has had a highly significant clinical impact on the diagnosis and prognostic stratification of patients with heart failure (HF). They are now an instrument with recognized value in this context and several studies have demonstrated their value in tailoring therapy for these patients. Following the recent advent of angiotensin receptor-neprilysin inhibitors (ARNIs), there is a need to review how these two biomarkers are interpreted in HF...
December 7, 2017: Portuguese Journal of Cardiology: An Official Journal of the Portuguese Society of Cardiology
https://www.readbyqxmd.com/read/29203527/a-novel-chemical-inducer-of-streptococcus-quorum-sensing-acts-by-inhibiting-the-pheromone-degrading-endopeptidase-pepo
#3
Tiara G Pérez Morales, Kiira Ratia, Duo-Sheng Wang, Artemis Gogos, Tom G Driver, Michael J Federle
Bacteria produce chemical signals (pheromones) to coordinate behaviors across a population in a process termed quorum sensing (QS). QS systems comprising peptide pheromones and their corresponding Rgg receptors are widespread among Firmicutes and may be useful targets for manipulating microbial behaviors, like suppressing virulence. The Rgg2/3 QS circuit of the human pathogen Streptococcus pyogenes controls genes affecting resistance to host lysozyme in response to short hydrophobic pheromones (SHPs). Considering that artificial activation of a QS pathway may be as useful in the objective of manipulating bacteria as inhibiting it, we sought to identify small-molecule inducers of the Rgg2/3 QS system...
December 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29196110/degradation-of-tropoelastin-and-skin-elastin-by-neprilysin
#4
Angela C Mora Huertas, Christian E H Schmelzer, Chiara Luise, Wolfgang Sippl, Markus Pietzsch, Wolfgang Hoehenwarter, Andrea Heinz
Neprilysin is also known as skin fibroblast-derived elastase, and its up-regulation during aging is associated with impairments of the elastic fiber network, loss of skin elasticity and wrinkle formation. However, information on its elastase activity is still limited. The aim of this study was to investigate the degradation of fibrillar skin elastin by neprilysin and the influence of the donor's age on the degradation process using mass spectrometry and bioinformatics approaches. The results showed that cleavage by neprilysin is dependent on previous damage of elastin...
November 28, 2017: Biochimie
https://www.readbyqxmd.com/read/29191928/sustained-activation-of-rho-gtpases-promotes-a-synthetic-pulmonary-artery-smooth-muscle-cell-phenotype-in-neprilysin-null-mice
#5
Vijaya Karoor, Mehdi A Fini, Zoe Loomis, Timothy Sullivan, Louis B Hersh, Evgenia Gerasimovskaya, David Irwin, Edward C Dempsey
OBJECTIVE: Pulmonary artery smooth muscle cells (PASMCs) from neprilysin (NEP) null mice exhibit a synthetic phenotype and increased activation of Rho GTPases compared with their wild-type counterparts. Although Rho GTPases are known to promote a contractile SMC phenotype, we hypothesize that their sustained activity decreases SM-protein expression in these cells. APPROACH AND RESULTS: PASMCs isolated from wild-type and NEP-/- mice were used to assess levels of SM-proteins (SM-actin, SM-myosin, SM22, and calponin) by Western blotting, and were lower in NEP-/- PASMCs compared with wild-type...
November 30, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29190943/neuroprotective-effects-of-bajijiasu-against-cognitive-impairment-induced-by-amyloid-%C3%AE-in-app-ps1-mice
#6
Haobin Cai, Yijie Wang, Jiayang He, Tiantian Cai, Jun Wu, Jiansong Fang, Rong Zhang, Zhouke Guo, Li Guan, Qinkai Zhan, Li Lin, Yao Xiao, Huafeng Pan, Qi Wang
Alzheimer's disease (AD) is a progressive neurological degenerative disease. The main clinical manifestations of AD include progressive cognitive impairment and alteration of personality. Senile plaques, neuroinflammation, and destruction of synapse structure stability are the main pathological features of AD. Bajijiasu(BJJS) is extracted from Morinda Officinalis, a Chinese herb. In this study, we explored the effect of BJJS on AD from many aspects in APPswe/PSEN1ΔE9 (APP/PS1) double transgenic mice. The Morris water maze and novel object recognition tests results showed that BJJS could significantly improve the learning and memory abilities in APP/PS1 mice...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29187381/crrl269-a-novel-designer-and-renal-enhancing-pgc-a-peptide-activator
#7
Yang Chen, Gail J Harty, Brenda K Huntley, Seethalakshmi R Iyer, Denise M Heublein, Gerald E Harders, Laura M G Meems, Shuchong Pan, S Jeson Sangaralingham, Tomoko Ichiki, John C Burnett
AIMS: The natriuretic peptides (NPs) b-type NP (BNP) and urodilatin (URO) exert renal protective properties via the particulate guanylyl cyclase A receptor (pGC-A). As a potential renal enhancing strategy, we engineered a novel designer peptide that we call CRRL269. CRRL269 was investigated in human cell lines and in normal canines to define potential cardiorenal enhancing actions. The mechanism of its cardiorenal selective properties was also investigated. METHODS AND RESULTS: In vitro NP receptor activity was quantified with 3', 5' cyclic guanosine monophosphate (cGMP) generation...
November 29, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29180454/effect-of-sacubitril-valsartan-on-exercise-induced-lipid-metabolism-in-patients-with-obesity-and-hypertension
#8
Stefan Engeli, Rudi Stinkens, Tim Heise, Marcus May, Gijs H Goossens, Ellen E Blaak, Bas Havekes, Thomas Jax, Diego Albrecht, Parasar Pal, Uwe Tegtbur, Sven Haufe, Thomas H Langenickel, Jens Jordan
Sacubitril/valsartan (LCZ696), a novel angiotensin receptor-neprilysin inhibitor, was recently approved for the treatment of heart failure with reduced ejection fraction. Neprilysin degrades several peptides that modulate lipid metabolism, including natriuretic peptides. In this study, we investigated the effects of 8 weeks' treatment with sacubitril/valsartan on whole-body and adipose tissue lipolysis and lipid oxidation during defined physical exercise compared with the metabolically neutral comparator amlodipine...
November 27, 2017: Hypertension
https://www.readbyqxmd.com/read/29161341/distinct-spatiotemporal-accumulation-of-n-truncated-and-full-length-amyloid-%C3%AE-42-in-alzheimer-s-disease
#9
Mitsuru Shinohara, Shunsuke Koga, Takuya Konno, Jeremy Nix, Motoko Shinohara, Naoya Aoki, Pritam Das, Joseph E Parisi, Ronald C Petersen, Terrone L Rosenberry, Dennis W Dickson, Guojun Bu
Accumulation of amyloid-β peptides is a dominant feature in the pathogenesis of Alzheimer's disease; however, it is not clear how individual amyloid-β species accumulate and affect other neuropathological and clinical features in the disease. Thus, we compared the accumulation of N-terminally truncated amyloid-β and full-length amyloid-β, depending on disease stage as well as brain area, and determined how these amyloid-β species respectively correlate with clinicopathological features of Alzheimer's disease...
November 17, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29153212/-new-treatments-for-heart-failure
#10
Clément Venner, Olivier Huttin, Christine Selton-Suty, Yves Juillière
New direct oral anticoagulants are recommended as first-line therapy in case of atrial fibrillation within a heart failure. In the absence of atrial fibrillation, the role for new direct oral anticoagulants would have to be confirmed in the next years. Sacubitril/valsartan, angiotansin II receptor neprilysin inhibitor, presents with an efficacy superior to that of angiotensin converting enzyme inhibitors. It is now recommended in the treatment of heart failure as a third-line therapy. Modalities of prescription are strict, and safety is good...
November 2017: Soins; la Revue de Référence Infirmière
https://www.readbyqxmd.com/read/29153198/n-terminal-b-type-natriuretic-peptide-in-heart-failure
#11
REVIEW
Arthur Mark Richards
Plasma amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is a guideline-mandated biomarker in heart failure (HF). Used as an inclusion criterion for therapeutic trials, NT-proBNP enriches trial populations and is a valid surrogate endpoint. Its diagnostic performance is best validated in acute decompensated HF (ADHF). NT-proBNP offers prognostic information independent of standard clinical predictors and refines risk stratification. With the advent of combined angiotensin 2 type 1 receptor blockade and neprilysin inhibition (ARNI) NT-proBNP retains its relationship to cardiac status and is the marker of choice in assessment of possible ADHF and in serial monitoring of HF patients receiving ARNI treatment...
January 2018: Heart Failure Clinics
https://www.readbyqxmd.com/read/29146274/effects-of-angiotensin-neprilysin-inhibition-as-compared-to-angiotensin-inhibition-on-ventricular-arrhythmias-in-reduced-ejection-fraction-patients-under-continuous-remote-monitoring-of-implantable-defibrillator-devices
#12
Carlos de Diego, Luis González-Torres, José María Núñez, Raúl Centurión Inda, David A Martin-Langerwerf, Antonio D Sangio, Piotr Chochowski, Pilar Casasnovas, Julio C Blazquéz, Jesús Almendral
BACKGROUND: Angiotensin-neprilysin inhibition as compared to angiotensin inhibition decreased sudden cardiac death in reduced ejection fraction heart failure (rEFHF). The precise mechanism remains unclear. OBJECTIVE: To explore the effect of angiotensin-neprilysin inhibition on ventricular arrhythmias as compared to angiotensin inhibition in rEFHF patients with an implantable cardiac defibrillator (ICD) and remote monitoring. METHODS: We prospectively included 120 patients with ICD and: 1) New York Heart Association functional class≥ II, 2) left ventricular ejection fraction (LVEF) ≤40%, 3) remote monitoring...
November 13, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/29137346/safety-of-the-neprilysin-renin-angiotensin-system-inhibitor-lcz696
#13
REVIEW
Bo Li, Yunhe Zhao, Bo Yin, Mengfei Helian, Xinmei Wang, Feng Chen, Hongxia Zhang, Hui Sun, Bin Meng, Fengshuang An
Objectives: The combined neprilysin/rennin-angiotensin system inhibitor sacubitril/valsartan (LCZ696) has shown its superiority over ACEI/ARB therapy. In view of the existing concern of its adverse effects, we aimed to provide evidence of the safety of the new drug. Results: A total of 6 randomized trials with 11,821 subjects were included in this analysis. No significant differences were found in any adverse effects between LCZ696 and ACEI/ARB or placebo groups...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29129252/design-for-the-sacubitril-valsartan-lcz696-compared-with-enalapril-study-of-pediatric-patients-with-heart-failure-due-to-systemic-left-ventricle-systolic-dysfunction-panorama-hf-study
#14
RANDOMIZED CONTROLLED TRIAL
Robert Shaddy, Charles Canter, Nancy Halnon, Lazaros Kochilas, Joseph Rossano, Damien Bonnet, Christopher Bush, Ziqiang Zhao, Paul Kantor, Michael Burch, Fabian Chen
BACKGROUND: Sacubitril/valsartan (LCZ696) is an angiotensin receptor neprilysin inhibitor approved for the treatment of adult heart failure (HF); however, the benefit of sacubitril/valsartan in pediatric HF patients is unknown. STUDY DESIGN: This global multi-center study will use an adaptive, seamless two-part design. Part 1 will assess the pharmacokinetics/pharmacodynamics of single ascending doses of sacubitril/valsartan in pediatric (1 month to <18 years) HF patients with systemic left ventricle and reduced left ventricular systolic function stratified into 3 age groups (Group 1: 6 to <18 years; Group 2: 1 to <6 years; Group 3: 1 month to <1 year)...
November 2017: American Heart Journal
https://www.readbyqxmd.com/read/29091918/software-aided-approach-to-investigate-peptide-structure-and-metabolic-susceptibility-of-amide-bonds-in-peptide-drugs-based-on-high-resolution-mass-spectrometry
#15
Tatiana Radchenko, Andreas Brink, Yves Siegrist, Christopher Kochansky, Alison Bateman, Fabien Fontaine, Luca Morettoni, Ismael Zamora
Interest in using peptide molecules as therapeutic agents due to high selectivity and efficacy is increasing within the pharmaceutical industry. However, most peptide-derived drugs cannot be administered orally because of low bioavailability and instability in the gastrointestinal tract due to protease activity. Therefore, structural modifications peptides are required to improve their stability. For this purpose, several in-silico software tools have been developed such as PeptideCutter or PoPS, which aim to predict peptide cleavage sites for different proteases...
2017: PloS One
https://www.readbyqxmd.com/read/29084021/what-will-be-the-impact-of-sacubitril-valsartan-in-clinical-practice
#16
Marco Metra
: The Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial has shown a reduction in the risk of death and heart failure hospitalizations with sacubitril/valsartan, compared with enalapril, in patients with heart failure and reduced ejection fraction. Guidelines now recommend the substitution of angiotensin-converting enzyme inhibitor or AT1 blockers with sacubitril/valsartan in the patients who remain symptomatic despite ongoing optimal treatment...
October 27, 2017: Journal of Cardiovascular Medicine
https://www.readbyqxmd.com/read/29050563/neprilysin-and-heart-failure-a-sympathetic-relationship
#17
EDITORIAL
Domingo A Pascual-Figal
No abstract text is available yet for this article.
October 24, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29050562/renal-sympathetic-denervation-protects%C3%A2-the-failing-heart-via-inhibition-of%C3%A2-neprilysin%C3%A2-activity-in-the-kidney
#18
David J Polhemus, Rishi K Trivedi, Juan Gao, Zhen Li, Amy L Scarborough, Traci T Goodchild, Kurt J Varner, Huijing Xia, Frank W Smart, Daniel R Kapusta, David J Lefer
BACKGROUND: Sustained sympathetic activation contributes to the progression of myocardial cell injury, cardiac fibrosis, and left ventricular (LV) dysfunction in heart failure (HF). OBJECTIVES: This study investigated the effects of radiofrequency renal nerve denervation (RF-RDN) on the pathobiology of HF and the interaction between the renal sympathetic nerves and natriuretic peptide (NP) metabolism. METHODS: Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were subjected to 45 min of coronary artery ligation and reperfusion for 12 weeks...
October 24, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29042791/profile-of-sacubitril-valsartan-in-the-treatment-of-heart-failure-patient-selection-and-perspectives
#19
REVIEW
Srikanth Yandrapalli, Gabriela Andries, Medha Biswas, Sahil Khera
With an estimated prevalence of 5.8 million in the USA and over 23 million people worldwide, heart failure (HF) is growing in epidemic proportions. Despite the use of guideline-directed medical therapies such as angiotensin-converting enzyme inhibitors, beta-adrenergic blockers, angiotensin receptor blockers, and mineralocorticoid receptor antagonists for chronic systolic HF for almost two decades, HF remains a leading cause of morbidity, mortality, and health care expenditures. The Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial provided compelling evidence for the cardiovascular and mortality benefit of sacubitril/valsartan when compared to enalapril in patients with heart failure and reduced ejection fraction (HFrEF)...
2017: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/29042424/angiotensin-ii-receptor-neprilysin-inhibitor-sacubitril-valsartan-improves-endothelial-dysfunction-in-spontaneously-hypertensive-rats
#20
Takunori Seki, Kenichi Goto, Yasuo Kansui, Toshio Ohtsubo, Kiyoshi Matsumura, Takanari Kitazono
BACKGROUND: We have previously demonstrated that antihypertensive treatment with renin-angiotensin system inhibitors restores the impaired endothelium-dependent hyperpolarization (EDH)-mediated responses in spontaneously hypertensive rats (SHRs). Herein, we investigated whether the angiotensin II receptor-neprilysin inhibitor sacubitril/valsartan (LCZ696) would improve reduced EDH-mediated responses and whether LCZ696 would exert additional effects on endothelium-dependent and endothelium-independent vasorelaxation compared with an angiotensin II type 1 receptor blocker alone during hypertension...
October 17, 2017: Journal of the American Heart Association
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