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https://www.readbyqxmd.com/read/28188358/protective-effect-of-valproic-acid-in-streptozotocin-induced-sporadic-alzheimer-s-disease-mouse-model-possible-involvement-of-the-cholinergic-system
#1
Mirna Ezzat Sorial, Nesrine Salah El Dine El Sayed
Sporadic Alzheimer's disease (SAD) is a slowly progressive neurological disorder that is the most common form of dementia. Cholinergic system dysfunction and amyloid beta formation are the two main underlying pathological mechanisms for the disease development. In recent studies, insulin receptor desensitization and disturbances in the downstream effects of insulin receptor signaling were observed in the brains of Alzheimer's patients. Currently, intracereberoventricular (ICV) injection of streptozotocin (STZ) is found to induce behavioral, neurochemical, and structural alterations in animals resembling those found in SAD patients...
February 10, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28186506/epigenetic-regulation-of-hdac1-sumoylation-as-an-endogenous-neuroprotection-against-a%C3%AE-toxicity-in-a-mouse-model-of-alzheimer-s-disease
#2
Chih Chieh Tao, Wei Lun Hsu, Yun Li Ma, Sin Jhong Cheng, Eminy Hy Lee
Amyloid-β (Aβ) produces neurotoxicity in the brain and causes neuronal death, but the endogenous defense mechanism that is activated on Aβ insult is less well known. Here we found that acute Aβ increases the expression of PIAS1 and Mcl-1 via activation of MAPK/ERK, and Aβ induction of PIAS1 enhances HDAC1 SUMOylation in rat hippocampus. Knockdown of PIAS1 decreases endogenous HDAC1 SUMOylation and blocks Aβ induction of Mcl-1. Sumoylated HDAC1 reduces it association with CREB, increases CREB binding to the Mcl-1 promoter and mediates Aβ induction of Mcl-1 expression...
February 10, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28185171/neprilysin-inhibitors-in-cardiovascular-disease
#3
REVIEW
Guson Kang, Dipanjan Banerjee
Mortality from heart failure remains high despite advances in medical therapy over the last three decades. Angiotensin receptor-neprilysin inhibitor (ARNI) combinations are the latest addition to the heart failure medical armamentarium, which is built on the cornerstone regimen of beta blockers, angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers, and aldosterone antagonists. Recent trial data have shown a significant mortality benefit from ARNIs, which, as of May 2016, have now received a class I recommendation for use in patients with heart failure and reduced ejection fraction from the major American and European cardiology societies...
February 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28178694/resolution-of-cheyne-stokes-respiration-after-treatment-of-heart-failure-with-sacubitril-valsartan-a-first-case-report
#4
Henrik Fox, Thomas Bitter, Dieter Horstkotte, Olaf Oldenburg
Sleep-disordered breathing (SDB) is highly prevalent in patients with heart failure (HF), and is known to be associated with a worse prognosis. The severity of central sleep apnea is thought to mirror cardiac dysfunction. The novel angiotensin receptor-neprilysin inhibitor (ARNi) sacubitril has been shown to improve HF, but a relationship between treatment with ARNi and the severity of SDB has not yet been investigated. We report the case of a 71-year-old male with HF and SDB. Treatment with sacubitril/valsartan was associated with improved cardiac function, as shown by a reduction in the level of N-terminal prohormone of brain natriuretic peptide from 3,249 to 1,720 pg/mL, and an improvement in left-ventricular ejection fraction from 30 to 35%...
February 9, 2017: Cardiology
https://www.readbyqxmd.com/read/28176630/novel-drugs-for-hypertension-and-heart-failure-struggling-for-a-place-under-the-sun
#5
Charles Faselis, Chrysoula Boutari, Michael Doumas, Konstantinos Imprialos, Konstantinos Stavropoulos, Peter Kokkinos
BACKGOUND: Current drug therapy for the management of arterial hypertension and heart failure has provided substantial benefits but has also some limitations. LCZ696, a dual inhibitor of angiotensin receptor blockers and neprilysin, and finerenone, a non-steroidal mineralocorticoid receptor antagonist, are two recently developed novel agents for the management of these conditions. METHODS: This review aims to present the pathophysiological basis for the use of these two novel drugs, critically discuss available clinical data, and provide future perspectives...
February 6, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28176581/correction
#6
(no author information available yet)
There was an error in our CPD article Chronic heart failure part 2: treatment and management (11 January). On page 55, the first sentence in the angiotensin receptor neprilysin inhibitor section should read: Valsartan with sacubitril is an angiotensin receptor neprilysin inhibitor that has recently been approved for use as a replacement for ACE inhibitors, to further reduce the risk of hospitalisation and death in ambulatory patients with heart failure and an ejection fraction ≤35% who remain symptomatic despite optimal treatment with an ACE inhibitor, a beta-blocker and an aldersterone antagonist (Ponikowski et al 2016)...
February 8, 2017: Nursing Standard
https://www.readbyqxmd.com/read/28133468/changing-the-treatment-of-heart-failure-with-reduced-ejection-fraction-clinical-use-of-sacubitril-valsartan-combination
#7
REVIEW
Edgardo Kaplinsky
Despite significant therapeutic advances, patients with chronic heart failure (HF) remain at high risk of morbidity and mortality. Sacubitril valsartan (previously known as LCZ696) is a new oral agent approved for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. It is described as the first in class angiotensin receptor neprilysin inhibitor (ARNI) since it incorporates the neprilysin inhibitor, sacubitril and the angiotensin II receptor antagonist, valsartan. Neprilysin is an endopeptidase that breaks down several vasoactive peptides including natriuretic peptides (NPs), bradykinin, endothelin and angiotensin II (Ang-II)...
November 2016: Journal of Geriatric Cardiology: JGC
https://www.readbyqxmd.com/read/28129699/advances-in-the-pharmacotherapy-of-chronic-heart-failure-with-preserved-ejection-fraction-an-ideal-opportunity-for-precision-medicine
#8
Vincenzo B Polsinelli, Sanjiv J Shah
Heart failure with preserved ejection fraction (HFpEF), which comprises approximately 50% of all heart failure patients, is a challenging and complex clinical syndrome that is often thought to lack effective treatments. Areas covered: Despite the common mantra that HFpEF has no effective treatments, closer inspection of HFpEF clinical trials reveals that several of the drugs tested are associated with benefits in exercise capacity and quality of life, and reduction in heart failure hospitalization. Here we review major randomized controlled trials in HFpEF, focusing on renin-angiotensin-aldosterone system antagonists, organic nitrates, digoxin, beta-blockers, and phosphodiesterase-5 inhibitors...
January 27, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28123645/dynamic-alteration-of-neprilysin-and-endothelin-converting-enzyme-in-age-dependent-appswe-ps1de9-mouse-model-of-alzheimer-s-disease
#9
Li Zhou, Jianxu Liu, Dong Dong, Chunsheng Wei, Rui Wang
Imbalance of Aβ production and Aβ removal leads to Aβ accumulation. Aβ degrading enzyme (including neprilysin-NEP, endothelin converting enzyme-ECE) as a therapeutic strategy for lowering brain Aβ deposition has attracted increasing attention. In this study, we investigated alteration of age and region-dependent in APP/PS1 double transgenic mice (3, 6, 9, 12 months) and their age-matched wild type mice including the ability of spatial memory, Aβ deposits, the protein expression, location and activity of NEP and ECE...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28120597/paramount-importance-of-angiotensin-receptor-neprilysin-inhibitor-in-heart-failure-management
#10
Hilman Zulkifli Amin, Lukman Zulkifli Amin, Firman Zulkifli Amin
No abstract text is available yet for this article.
December 2016: Acta Medica Iranica
https://www.readbyqxmd.com/read/28103595/identification-of-small-peptides-in-human-cerebrospinal-fluid-upon-amyloid-%C3%AE-degradation
#11
Naoki Mizuta, Kanta Yanagida, Takashi Kodama, Takeshi Tomonaga, Mako Takami, Hiroshi Oyama, Takashi Kudo, Manabu Ikeda, Masatoshi Takeda, Shinji Tagami, Masayasu Okochi
BACKGROUND: Amyloid-β (Aβ) degradation in brains of Alzheimer disease patients is a crucial focus for the clarification of disease pathogenesis. Nevertheless, the mechanisms underlying Aβ degradation in the human brain remain unclear. OBJECTIVE: This study aimed to quantify the levels of small C-terminal Aβ fragments generated upon Aβ degradation in human cerebrospinal fluid (CSF). METHODS: A fraction containing small peptides was isolated and purified from human CSF by high-pressure liquid chromatography...
2017: Neuro-degenerative Diseases
https://www.readbyqxmd.com/read/28093466/effects-of-sacubitril-valsartan-versus-olmesartan-on-central-hemodynamics-in-the-elderly-with-systolic-hypertension-the-parameter-study
#12
Bryan Williams, John R Cockcroft, Kazuomi Kario, Dion H Zappe, Patrick C Brunel, Qian Wang, Weinong Guo
Effective treatment of systolic hypertension in elderly patients remains a major therapeutic challenge. A multicenter, double-blind, randomized controlled trial with sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, was conducted to determine its effects versus olmesartan (angiotensin receptor blocker) on central aortic pressures, in elderly patients (aged ≥60 years) with systolic hypertension and pulse pressure >60 mm Hg, indicative of arterial stiffness. Patients (n=454; mean age, 67...
March 2017: Hypertension
https://www.readbyqxmd.com/read/28087688/thirty-years-of-evidence-on-the-efficacy-of-drug-treatments-for-chronic-heart-failure-with-reduced-ejection-fraction-a-network-meta-analysis
#13
Heather Burnett, Amy Earley, Adriaan A Voors, Michele Senni, John J V McMurray, Celine Deschaseaux, Shannon Cope
BACKGROUND: Treatments that reduce mortality and morbidity in patients with heart failure with reduced ejection fraction, including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), β-blockers (BB), mineralocorticoid receptor antagonists (MRA), and angiotensin receptor-neprilysin inhibitors (ARNI), have not been studied in a head-to-head fashion. This network meta-analysis aimed to compare the efficacy of these drugs and their combinations regarding all-cause mortality in patients with heart failure with reduced ejection fraction...
January 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28078611/hyperbaric-oxygen-prevents-cognitive-impairments-in-mice-induced-by-d-galactose-by-improving-cholinergic-and-anti-apoptotic-functions
#14
Chunxia Chen, Luying Huang, Zhihuan Nong, Yaoxuan Li, Wan Chen, Jianping Huang, Xiaorong Pan, Guangwei Wu, Yingzhong Lin
Our previous study demonstrated that hyperbaric oxygen (HBO) improved cognitive impairments mainly by regulating oxidative stress, inflammatory responses and aging-related gene expression. However, a method for preventing cognitive dysfunction has yet to be developed. In the present study, we explored the protective effects of HBO on the cholinergic system and apoptosis in D-galactose (D-gal)-treated mice. A model of aging was established via systemic intraperitoneal injection of D-gal daily for 8 weeks. HBO was administered during the last 2 weeks of D-gal injection...
January 11, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28076404/combined-inhibition-of-the-renin-angiotensin-system-and-neprilysin-positively-influences-complex-mitochondrial-adaptations-in-progressive-experimental-heart-failure
#15
Laura Grois, Julian Hupf, Jörg Reinders, Josef Schröder, Alexander Dietl, Peter M Schmid, Carsten Jungbauer, Markus Resch, Lars S Maier, Andreas Luchner, Christoph Birner
BACKGROUND: Inhibitors of the renin angiotensin system and neprilysin (RAS-/NEP-inhibitors) proved to be extraordinarily beneficial in systolic heart failure. Furthermore, compelling evidence exists that impaired mitochondrial pathways are causatively involved in progressive left ventricular (LV) dysfunction. Consequently, we aimed to assess whether RAS-/NEP-inhibition can attenuate mitochondrial adaptations in experimental heart failure (HF). METHODS AND RESULTS: By progressive right ventricular pacing, distinct HF stages were induced in 15 rabbits, and 6 animals served as controls (CTRL)...
2017: PloS One
https://www.readbyqxmd.com/read/28075105/heart-failure-due-to-reduced-ejection-fraction-medical-management
#16
William E Chavey, Robrt V Hogikyan, R Van Harrison, John M Nicklas
Heart failure is an increasingly common condition resulting in high rates of morbidity and mortality. For patients who have heart failure and reduced ejection fraction, randomized clinical trials demonstrate consistent mortality benefit from angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, direct-acting vasodilators, beta blockers, and aldosterone antagonists. Additionally, some data show benefits from two new classes of drugs: angiotensin receptor blocker/neprilysin inhibitor and sinus node modulator...
January 1, 2017: American Family Physician
https://www.readbyqxmd.com/read/28062615/biochemistry-therapeutics-and-biomarker-implications-of-neprilysin-in-cardiorenal-disease
#17
REVIEW
Yang Chen, John C Burnett
BACKGROUND: Neprilysin (NEP) is a membrane-bound neutral endopeptidase that degrades a variety of bioactive peptides. The substrates include natriuretic peptides (NPs), which are important regulating mediators for cardiovascular and renal biology. Inhibition of NEP activity and exogenous NP administration thus have emerged as potential therapeutic strategies for treating cardiorenal diseases. More recently, B-type natriuretic peptide (BNP) or N-terminal-proBNP (NT-proBNP), 3'-5' cyclic guanosine monophosphate (cGMP), and soluble NEP as biomarkers have also been investigated in heart failure (HF) trials and their predictive value are beginning to be recognized...
January 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28060547/the-safety-of-sacubitril-valsartan-for-the-treatment-of-chronic-heart-failure
#18
Jeffrey M Tyler, John R Teerlink
Sacubitril-valsartan is a combination drug that contains the neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan. In 2015, the US Food and Drug Administration approved sacubitril-valsartan for treatment of heart failure patients with reduced ejection fraction and New York Heart Association class II-IV symptoms following a large, Phase III clinical trial (PARADIGM-HF) that demonstrated a 20% reduction in the combined primary end-point of death from cardiovascular cause or hospitalization for heart failure compared to enalapril...
January 6, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28040864/glp-1-receptor-independent-pathways-emerging-beneficial-effects-of-glp-1-breakdown-products
#19
REVIEW
Valeria Guglielmi, Paolo Sbraccia
The glucagon-like peptide-1 (GLP-1) axis has emerged as a major therapeutic target for the treatment of type 2 diabetes and, recently, of obesity. The insulinotropic activity of the native incretin hormone GLP-1(7-36)amide, which is mainly exerted through a unique G protein-coupled receptor (GLP-1R), is terminated via enzymatic cleavage by dipeptidyl peptidase-IV that generates a C-terminal GLP-1 metabolite GLP-1(9-36)amide, the major circulating form in plasma. GLP-1(28-36)amide and GLP-1(32-36)amide are further cleavage products derived from GLP-1(7-36)amide and GLP-1(9-36)amide by the action of a neutral endopeptidase known as neprilysin...
December 31, 2016: Eating and Weight Disorders: EWD
https://www.readbyqxmd.com/read/28030431/efficacy-and-safety-of-sacubitril-valsartan-lcz696-add-on-to-amlodipine-in-asian-patients-with-systolic-hypertension-uncontrolled-with-amlodipine-monotherapy
#20
Ji-Guang Wang, Kimihiko Yukisada, Antonio Sibulo, Kudsia Hafeez, Yan Jia, Jack Zhang
OBJECTIVE: The objective of this study is to evaluate the efficacy and safety of sacubitril/valsartan (LCZ696, an angiotensin receptor and neprilysin inhibitor) add-on to amlodipine compared with amlodipine monotherapy in Asian patients with systolic hypertension uncontrolled with amlodipine. METHODS: Patients with mean clinic SBP at least 145 mmHg and less than 180 mmHg after a 4-week treatment with amlodipine 5 mg/day were randomized to receive LCZ696/amlodipine (200/5 mg/day) or amlodipine 5 mg/day for 8 weeks...
December 24, 2016: Journal of Hypertension
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