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https://www.readbyqxmd.com/read/29029087/the-effect-of-sacubitril-valsartan-compared-to-olmesartan-on-cardiovascular-remodelling-in-subjects-with-essential-hypertension-the-results-of-a-randomized-double-blind-active-controlled-study
#1
Roland E Schmieder, Frank Wagner, Michael Mayr, Christian Delles, Christian Ott, Christian Keicher, Maja Hrabak-Paar, Tobias Heye, Solveig Aichner, Yasser Khder, Denise Yates, Diego Albrecht, Thomas Langenickel, Patrick Freyhardt, Rolf Janka, Jens Bremerich
Aims: Progressive aortic stiffening eventually leads to left ventricular (LV) hypertrophy and heart failure if left untreated. Anti-hypertensive agents have been shown to reverse this to some extent. The effects of sacubitril/valsartan (LCZ696), a dual-action angiotensin receptor blocker (ARB), and neprilysin inhibitor, on arterial stiffness and LV remodelling have not been investigated. Methods and results: This was a randomized, multi-centre, double-blind, double-dummy, active-controlled, parallel group, study to compare the effects on cardiovascular remodelling of sacubitril/valsartan with those of olmesartan in patients with hypertension and elevated pulse pressure...
September 27, 2017: European Heart Journal
https://www.readbyqxmd.com/read/29021382/sustained-activation-of-guanylate-cyclase-a-with-tdt-a-natriuretic-peptide-derivative-exhibits-cardiorenal-protection-in-dahl-salt-sensitive-hypertensive-rats
#2
Shohei Oishi, Naoko Suzuki, Yuri Hasui, Tsuyoshi Homma, Masanori Obana, Takahiro Nagayama, Yasushi Fujio
Heart failure often presents with prognosis-relevant impaired renal function. To investigate whether the chronic activation of guanylate cyclase-A (GC-A) protects both heart and kidney, we examined the effects of TDT, a neprilysin (NEP)-resistant natriuretic peptide (NP) derivative, on cardiac and renal dysfunction in Dahl salt-sensitive hypertensive rats (DS rats). Pretreatment with NEP or NEP inhibitor did not influence GC-A activation by TDT both in vitro and in vivo, resulting in a long-acting profile of TDT compared to native human atrial NP (hANP)...
October 11, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29018938/heart-failure-with-preserved-ejection-fraction-current-management-and-future-strategies-expert-opinion-on-the-behalf-of-the-nucleus-of-the-heart-failure-working-group-of-the-german-society-of-cardiology-dkg
#3
REVIEW
Carsten Tschöpe, Christoph Birner, Michael Böhm, Oliver Bruder, Stefan Frantz, Andreas Luchner, Lars Maier, Stefan Störk, Behrouz Kherad, Ulrich Laufs
About 50% of all patients suffering from heart failure (HF) exhibit a reduced ejection fraction (EF ≤ 40%), termed HFrEF. The others may be classified into HF with midrange EF (HFmrEF 40-50%) or preserved ejection fraction (HFpEF, EF ≥ 50%). Presentation and pathophysiology of HFpEF is heterogeneous and its management remains a challenge since evidence of therapeutic benefits on outcome is scarce. Up to now, there are no therapies improving survival in patients with HFpEF. Thus, the treatment targets symptom relief, quality of life and reduction of cardiac decompensations by controlling fluid retention and managing risk factors and comorbidities...
October 10, 2017: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://www.readbyqxmd.com/read/28992296/efficacy-and-safety-of-sacubitril-valsartan-lcz696-compared-with-olmesartan-in-elderly-asian-patients-%C3%A2-65-years-with-systolic-hypertension
#4
Ouppatham Supasyndh, Jian'an Wang, Kudsia Hafeez, Ying Zhang, Jack Zhang, Hiromi Rakugi
OBJECTIVE: Systolic hypertension is common in elderly patients and remains a challenge to treat effectively. The efficacy and safety of sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, vs. olmesartan was evaluated in elderly Asian patients (≥65 years) with systolic hypertension. METHODS: In this randomized, double-blind, 14-week study, patients initially received once-daily sacubitril/valsartan 100 mg or olmesartan 10 mg, increased to sacubitril/valsartan 200 mg or olmesartan 20 mg at week 4...
July 11, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28984670/neprilysin-inhibition-and-the-treatment-of-heart-failure-recent-steps-in-the-right-direction
#5
Nicholas Bartell, William H Frishman
Numerous investigators have attempted to target the natriuretic peptide system in the treatment of heart failure since it was first described over 30 years ago. The history of neprilysin inhibition as a treatment for heart failure has been characterized by numerous setbacks. Recently, the PARADIGM-HF trial has shown favorable results, which may bring neprilysin inhibition into the mainstream of clinical practice. This article will review the history of the natriuretic peptide system and the investigations into it as a target for heart failure treatment, culminating in the positive results of the PARADIGM-HF trial, as well as planned and potential future directions for research...
November 2017: Cardiology in Review
https://www.readbyqxmd.com/read/28963831/-neprilysin-inhibition-and-chronic-kidney-disease
#6
REVIEW
Luca Di Lullo, Claudio Ronco, Antonio Bellasi, Mario Cozzolino, Fulvio Floccari, Vincenzo Barbera, Simone Verdesca, Rodolfo Rivera, Antonio De Pascalis, Anna Mudoni, Antonio Santoro
Patients with chronic kidney disease (CKD) have a higher incidence of cardiovascular (acute and chronic) events, which in turn have an increased risk of progression to end-stage renal disease (ESRD) Inhibition of neprilysin, in addition to offering a new therapeutic target in patients with heart failure, could represent a potential improvement strategy in cardiovascular and renal outcome of patients with CKD. Inhibition of neprilysin by inhibiting the breakdown of natriuretic peptides, increases their bioavailability resulting in an increase in diuresis and sodium excretion and, in addition to exerting an inhibition of the renin-angiotensin-aldosterone (RAAS) system...
September 28, 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28944989/the-combination-of-valsartan-and-sacubitril-in-the-treatment-of-hypertension-and-heart-failure-an-update
#7
REVIEW
Peter Munch Nielsen, Daniela Grimm, Markus Wehland, Ulf Simonsen, Marcus Krüger
A novel antihypertensive drug, LCZ696 (Entresto®), has recently been introduced, which combines the action of an antagonist of the renin-angiotensin-aldosterone system (RAAS), effectively decreasing the blood pressure, with an inhibition of neprilysin, which is responsible for metabolizing natriuretic peptides exerting antihypertensive and antifibrotic effects. In this MiniReview, we describe the pharmacokinetics and pharmacodynamics, efficacy and side effects of the combined angiotensin receptor antagonist and neprilysin inhibitor LCZ696...
September 25, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28931572/drosophila-neprilysin-1-rescues-memory-deficits-caused-by-amyloid-%C3%AE-peptide
#8
Oriane Turrel, Valérie Goguel, Thomas Preat
Neprilysins are type-II metalloproteinases known to degrade and inactivate a number of small peptides, in particular the mammalian amyloid-β peptide (Aβ). In Drosophila, several neprilysins expressed in the brain are required for middle-term (MTM) and long-term memory (LTM) in the dorsal paired medial (DPM) neurons, a pair of large neurons that broadly innervate the mushroom bodies (MB), the center of olfactory memory. These data indicate that one or several peptides need to be degraded for MTM and LTM. We have previously shown that the fly amyloid precursor protein (APPL) is required for memory in the MB...
September 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28879633/the-initial-evaluation-and-management-of-a-patient-with-heart-failure
#9
REVIEW
Jamael Hoosain, Jabar Whittier, Farhan Hasni, Shelley Hankins
PURPOSE OF REVIEW: The goal of this review is to summarize and discuss a thorough and effective manner in the evaluation of the patient with heart failure. RECENT FINDINGS: Heart failure is a prevalent disease worldwide and while the diagnosis of heart failure has remained relatively unchanged via a careful history and physical examination, identification of the etiology of the heart failure and treatment has made significant advances. Mechanical circulatory support (MCS), neprilysin inhibitors, and chronic resynchronization therapy (CRT) are just some of the relatively recent therapies afforded to assist heart failure patients...
September 6, 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28871373/-acute-and-chronic-heart-failure
#10
K-P Kresoja, G Schmidt, B Kherad, F Krackhardt, F Spillmann, C Tschöpe
The initial therapy of chronic heart failure is still based on diuretics, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers and in specific cases mineralocorticoid receptor antagonists. The new European Society of Cardiology (ESC) guidelines published in 2016 introduced angiotensin-receptor-neprilysin inhibitors, such as sacubitril/valsartan (LCZ 696) as new therapeutic agents in patients with chronic and progressive heart failure. New subgroup analyses for LCZ 696 have been published showing a beneficial effect in the context of various comorbidities, such as renal insufficiency, diabetes and hypotension...
September 4, 2017: Herz
https://www.readbyqxmd.com/read/28862951/serum-neprilysin-and-recurrent-admissions-in-patients-with-heart-failure
#11
Julio Núñez, Eduardo Núñez, Jaume Barallat, Vicent Bodí, Gema Miñana, M Cruz Pastor, Juan Sanchis, Josep Lupón, Antoni Bayes-Genis
BACKGROUND: Our aim was to evaluate the association between the soluble form of neprilysin (sNEP) levels and long-term all-cause, cardiovascular, and acute heart failure (AHF) recurrent admissions in an ambulatory cohort of patients with heart failure. sNEP has emerged as a new biomarker with promising implications for prognosis and therapy in patients with heart failure. Reducing the recurrent admission rate of heart failure patients has become an important target of public health planning strategies...
August 18, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28855494/charcot-marie-tooth-disease-type-2-caused-by-homozygous-mme-gene-mutation-superimposed-by-chronic-inflammatory-demyelinating-polyneuropathy
#12
Miwako Fujisawa, Yasuteru Sano, Masatoshi Omoto, Jyun-Ichi Ogasawara, Michiaki Koga, Hiroshi Takashima, Takashi Kanda
We report a 59-year-old Japanese male who developed gradually worsening weakness and numbness of distal four extremities since age 50. His parents were first cousins, and blood and cerebral spinal examinations were unremarkable. Homozygous mutation of MME gene was detected and thus he was diagnosed as autosomal-recessive Charcot-Marie-Tooth disease 2T (AR-CMT2T); however, electrophysiological examinations revealed scattered demyelinative changes including elongated terminal latency in several peripheral nerve trunks...
September 30, 2017: Rinshō Shinkeigaku, Clinical Neurology
https://www.readbyqxmd.com/read/28844335/sacubitril-valsartan-an-important-piece-in-the-therapeutic-puzzle-of-heart-failure
#13
REVIEW
Pedro Marques da Silva, Carlos Aguiar
Sacubitril/valsartan (LCZ696), a supramolecular sodium salt complex of the neprilysin inhibitor prodrug sacubitril and the angiotensin receptor blocker (ARB) valsartan, was recently approved in the EU and the USA for the treatment of chronic heart failure (HF) with reduced ejection fraction (HFrEF) (NYHA class II-IV). Inhibition of chronically activated neurohormonal pathways (the renin-angiotensin-aldosterone system [RAAS] and sympathetic nervous system [SNS]) is central to the treatment of chronic HFrEF. Furthermore, enhancement of the natriuretic peptide (NP) system, with favorable cardiovascular (CV) and renal effects in HF, is a desirable therapeutic goal to complement RAAS and SNS blockade...
August 23, 2017: Portuguese Journal of Cardiology: An Official Journal of the Portuguese Society of Cardiology
https://www.readbyqxmd.com/read/28844104/co-administration-of-tio2-nanowired-mesenchymal-stem-cells-with-cerebrolysin-potentiates-neprilysin-level-and-reduces-brain-pathology-in-alzheimer-s-disease
#14
Hari Shanker Sharma, Dafin Fior Muresanu, José Vicente Lafuente, Ranjana Patnaik, Z Ryan Tian, Asya Ozkizilcik, Rudy J Castellani, Herbert Mössler, Aruna Sharma
Neprilysin (NPL), the rate-limiting enzyme for amyloid beta peptide (AβP), appears to play a crucial role in the pathogenesis of Alzheimer's disease (AD). Since mesenchymal stem cells (MSCs) and/or cerebrolysin (CBL, a combination of neurotrophic factors and active peptide fragments) have neuroprotective effects in various CNS disorders, we examined nanowired delivery of MSCs and CBL on NPL content and brain pathology in AD using a rat model. AD-like symptoms were produced by intraventricular (i.c.v.) administration of AβP (1-40) in the left lateral ventricle (250 ng/10 μl, once daily) for 4 weeks...
August 26, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28844000/epigallocatechin-gallate-induces-extracellular-degradation-of-amyloid-%C3%AE-protein-by-increasing-neprilysin-secretion-from-astrocytes-through-activation-of-erk-and-pi3k-pathways
#15
Naoki Yamamoto, Mari Shibata, Ryo Ishikuro, Mamoru Tanida, Yuina Taniguchi, Yuri Ikeda-Matsuo, Kazuya Sobue
Amyloid-β (Aβ) production and clearance in the brain is a crucial focus of investigations into the pathogenesis of Alzheimer disease. Imbalance between production and clearance leads to accumulation of Aβ. The important Aβ-degrading enzymes in the brain are neprilysin (NEP) and insulin-degrading enzyme (IDE), and defective enzyme expression may facilitate Aβ deposition in sporadic late-onset AD patients. It has been suggested that epigallocatechin gallate (EGCG), a member of the catechin family, might be an effective treatment for AD, because it has been shown to elevate NEP expression...
August 24, 2017: Neuroscience
https://www.readbyqxmd.com/read/28837568/progranulin-gene-delivery-reduces-plaque-burden-and-synaptic-atrophy-in-a-mouse-model-of-alzheimer-s-disease
#16
Jackalina M Van Kampen, Denis G Kay
Progranulin (PGRN) is a multifunctional protein that is widely expressed throughout the brain, where it has been shown to act as a critical regulator of CNS inflammation and also functions as an autocrine neuronal growth factor, important for long-term neuronal survival. PGRN has been shown to activate cell signaling pathways regulating excitoxicity, oxidative stress, and synaptogenesis, as well as amyloidogenesis. Together, these critical roles in the CNS suggest that PGRN has the potential to be an important therapeutic target for the treatment of various neurodegenerative disorders, particularly Alzheimer's disease (AD)...
2017: PloS One
https://www.readbyqxmd.com/read/28809748/new-issues-on-measurement-of-b-type-natriuretic-peptides
#17
Aldo Clerico, Martina Zaninotto, Claudio Passino, Mario Plebani
The measurement of the active hormone of B-type natriuretic peptide (BNP) system actually has several analytical limitations and difficulties in clinical interpretations compared to that of inactive peptide N-terminal proBNP (NT-proBNP) because of the different biochemical and pathophysiological characteristics of two peptides and quality specifications of commercial immunoassay methods used for their measurement. Because of the better analytical characteristics of NT-proBNP immunoassays and the easier pathophysiological and clinical interpretations of variations of NT-proBNP levels in patients with heart failure (HF), some authors claimed to measure the inactive peptide NT-proBNP instead of the active hormone BNP for management of HF patients...
August 15, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28805977/prevention-against-renal-damage-in-rats-with-subtotal-nephrectomy-by-sacubitril-valsartan-lcz696-a-dual-acting-angiotensin-receptor-neprilysin-inhibitor
#18
Kentaro Ushijima, Hitoshi Ando, Yusuke Arakawa, Kenichi Aizawa, Chisato Suzuki, Ken Shimada, Shu-Ichi Tsuruoka, Akio Fujimura
Although patients with chronic kidney disease (CKD) are at increased risk for end-stage renal disease and cardiovascular events, adequate drug therapies for preventing the deterioration of these conditions are still not established. This study was undertaken to evaluate a preventive effect of an angiotensin receptor-neprilysin inhibitor sacubitril/valsartan (LCZ696), which is converted to sacubitril and valsartan in the body, against the progression of renal disease in rats with subtotal nephrectomy, an animal model of human CKD...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28793821/the-effects-of-lcz696-in-patients-with-hypertension-compared-with-angiotensin-receptor-blockers-a-meta-analysis-of-randomized-controlled-trials
#19
Yang Zhao, Heng Yu, Xu Zhao, Ruixin Ma, Ningyin Li, Jing Yu
LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, has been demonstrated to have greater advantages in the treatment of heart failure compared with angiotensin-converting enzyme inhibitors, enalapril, or angiotensin receptor blockers (ARBs). However, studies that compared the efficacy and safety of LCZ696 against valsartan in patients with hypertension are limited. To provide further evidence for the benefits of LCZ696 and to make this assessment, a meta-analysis of randomized controlled trials (RCTs) was performed...
September 2017: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28791183/alterations-in-gene-expression-of-components-of-the-renin-angiotensin-system-and-its-related-enzymes-in-lung-cancer
#20
Benjamin Goldstein, Malav Trivedi, Robert C Speth
OBJECTIVES: The study assessed the existence and significance of associations between the expression of fifteen renin-angiotensin system component genes and lung adenocarcinoma. MATERIALS AND METHODS: NCBI's built-in statistical tool, GEO2R, was used to calculate Student's t-tests for the associations found in a DNA expression study of adenocarcinoma and matched healthy lung tissue samples. The raw data was processed with GeneSpring™ and then used to generate figures with and without Sidak's multiple comparison correction...
2017: Lung Cancer International
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