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https://www.readbyqxmd.com/read/28623750/lcz696-improves-cardiac-function-via-alleviating-drp1-mediated-mitochondrial-dysfunction-in-mice-with-doxorubicin-induced-dilated-cardiomyopathy
#1
Yan Xia, Zhangwei Chen, Ao Chen, Mingqiang Fu, Zhen Dong, Kai Hu, Xiangdong Yang, Yunzeng Zou, Aijun Sun, Juying Qian, Junbo Ge
AIMS: LCZ696, a novel angiotensin receptor neprilysin inhibitor, is effective in treating heart failure patients. Doxorubicin (DOX) is an effective antitumor medication but the cardiotoxicity limited its clinical use. In this study, we aimed to determine the effect of LCZ696 on DOX-induced cardiomyopathy in mice and in vitro and to explore related mechanisms focusing on fission protein dynamin-related protein 1 (Drp1). METHODS AND RESULTS: In human study, we found that myocardial fission protein Drp1 expression and its ser 616 phosphorylation were significantly increased in dilated cardiomyopathy (DCM) patients...
June 14, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28614052/safety-of-the-neprilysin-renin-angiotensin-system-inhibitor-lcz696
#2
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...
May 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28587858/rebamipide-reduces-amyloid-%C3%AE-1-42-a%C3%AE-42-production-and-ameliorates-a%C3%AE-43-lowered-cell-viability-in-cultured-sh-sy5y-human-neuroblastoma-cells
#3
Kenta Fukui, Kazuma Yachi, Hidemi Yoshida, Kunikazu Tanji, Tomoh Matsumiya, Ryo Hayakari, Kazushi Tsuruga, Hiroshi Tanaka, Tadaatsu Imaizumi
Amyloid-beta (Aβ) peptides, Aβ 1-42 (Aβ42) and Aβ43, in particular, have been implicated in the pathophysiology of neurodegenerative disease such as Alzheimer's disease (AD). Rebamipide (REB), a gastrointestinal protective drug, can cross the blood-brain barrier after oral administration; however, the effects of REB on neuronal cells have not yet been reported. In this study, we investigated the effects of REB on Aβ43-induced cytotoxicity (monomers, 10μM) in cultured SH-SY5Y human neuroblastoma cells...
June 3, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28587583/angiotensin-receptor-neprilysin-inhibition
#4
Ofer Havakuk, Uri Elkayam
The novel combination sacubitril/valsartan represents a new therapeutic approach in the management of heart failure. With the simultaneous blockage of the enzyme neprilysin (by sacubitril) and angiotensin II receptors (by valsartan), this combination reduces the degradation of natriuretic peptides and other counterregulatory peptide systems while avoiding the deleterious effect of angiotensin II receptors activation and thereby encompasses a beneficial impact of 2 important neurohormonal pathways activated in heart failure...
July 2017: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28577679/the-effects-of-sacubitril-valsartan-on-coronary-outcomes-in-paradigm-hf
#5
Ulrik M Mogensen, Lars Køber, Søren L Kristensen, Pardeep S Jhund, Jianjian Gong, Martin P Lefkowitz, Adel R Rizkala, Jean L Rouleau, Victor C Shi, Karl Swedberg, Michael R Zile, Scott D Solomon, Milton Packer, John J V McMurray
BACKGROUND: Angiotensin converting enzyme inhibitors (ACE-I), are beneficial both in heart failure with reduced ejection fraction (HF-REF) and after myocardial infarction (MI). We examined the effects of the angiotensin-receptor neprilysin inhibitor sacubitril/valsartan, compared with the ACE-I enalapril, on coronary outcomes in PARADIGM-HF. METHODS AND RESULTS: We examined the effect of sacubitril/valsartan compared with enalapril on the following outcomes: i) the primary composite endpoint of cardiovascular (CV) death or HF hospitalization, ii) a pre-defined broader composite including, in addition, MI, stroke, and resuscitated sudden death, and iii) a post hoc coronary composite of CV-death, non-fatal MI, angina hospitalization or coronary revascularization...
June 2017: American Heart Journal
https://www.readbyqxmd.com/read/28559246/neprilysin-is-required-for-angiotensin-1-7-s-ability-to-enhance-insulin-secretion-via-its-proteolytic-activity-to-generate-angiotensin-1-2
#6
Gurkirat S Brar, Breanne M Barrow, Matthew Watson, Ryan Griesbach, Edwina Choung, Andrew Welch, Bela Ruzsicska, Daniel P Raleigh, Sakeneh Zraika
Recent work has renewed interest in therapies targeting the renin-angiotensin system (RAS) to improve β-cell function in type 2 diabetes. Studies show that generation of angiotensin-(1-7) by angiotensin converting enzyme 2 (ACE2) and its binding to the Mas receptor (MasR) improves glucose homeostasis, partly by enhancing glucose-stimulated insulin secretion (GSIS). Thus, islet ACE2 upregulation is viewed as a desirable therapeutic goal. Here, we show that although endogenous islet ACE2 expression is sparse, its inhibition abrogates angiotensin-(1-7)-mediated GSIS...
May 30, 2017: Diabetes
https://www.readbyqxmd.com/read/28553432/hiv-1-transactivator-protein-induces-zo-1-and-neprilysin-dysfunction-in-brain-endothelial-cells-via-the-ras-signaling-pathway
#7
Wenlin Jiang, Wen Huang, Yanlan Chen, Min Zou, Dingyue Peng, Debing Chen
Amyloid beta (Aβ) deposition is increased in human immunodeficiency virus-1- (HIV-1-) infected brain, but the mechanisms are not fully understood. The aim of the present study was to evaluate the role of Ras signaling in HIV-1 transactivator protein- (Tat-) induced Aβ accumulation in human cerebral microvascular endothelial cells (HBEC-5i). Cell viability assay showed that 1 μg/mL Tat and 20 μmol/L of the Ras inhibitor farnesylthiosalicylic acid (FTS) had no significant effect on HBEC-5i cell viability after 24 h exposure...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28552863/atrial-natriuretic-peptide%C3%A3-old-but-new-therapeutic-in-cardiovascular-diseases
#8
Tomoko Ichiki, John C Burnett
With the discovery of atrial natriuretic peptide (ANP), the heart as an endocrine organ was established. Basic science revealed that ANP, through the particulate guanylyl cyclase A receptor and cGMP, plays a fundamental role in cardiorenal biology. This work has led to the development of ANP as a therapeutic, especially in heart failure (HF). Human genomics has strengthened our understanding of ANP, revealing specific ANP gene variants that may be associated with biological dysfunction, but also may mediate protective properties, including in metabolic syndrome...
May 27, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28545475/urinary-neprilysin-in-the-critically-ill-patient
#9
Sahra Pajenda, Karl Mechtler, Ludwig Wagner
BACKGROUND: Critically ill patients in intensive care face hazardous conditions. Among these, acute kidney injury (AKI) is frequently seen as a result of sepsis. Early diagnosis of kidney injury is of the utmost importance in the guidance of interventions or avoidance of treatment-induced kidney injury. On these grounds, we searched for markers that could indicate proximal tubular cell injury. METHODS: Urine samples of 90 patients admitted to the intensive or intermediate care unit were collected over 2 to 5 days...
May 25, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28527109/erratum-to-clinical-pharmacokinetics-of-sacubitril-valsartan-lcz696-a-novel-angiotensin-receptor-neprilysin-inhibitor
#10
Surya Ayalasomayajula, Thomas Langenickel, Parasar Pal, Sreedevi Boggarapu, Gangadhar Sunkara
Sacubitril/valsartan (LCZ696) is indicated for the treatment of heart failure with reduced ejection fraction. Absorption of sacubitril/valsartan and conversion of sacubitril (prodrug) to sacubitrilat (neprilysin inhibitor) was rapid with maximum plasma concentrations of sacubitril, sacubitrilat, and valsartan (angiotensin receptor blocker) reaching within 0.5, 1.5-2.0, and 2.0-3.0 h, respectively. With a twofold increase in dose, an increase in the area under the plasma concentration-time curve was proportional for sacubitril, ~1...
May 19, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28523441/progress-in-the-presence-of-failure-updates-in-chronic-systolic-heart-failure-management
#11
REVIEW
Katie M Murphy, Julie L Rosenthal
The therapeutic heart failure armamentarium has evolved from drugs to transplantation to devices through further understanding of its complex pathophysiology and pathogenesis. Current medications capitalize on our evolving understanding of the sympathetic and renin-angiotensin-aldosterone systems that subsequently promote both beneficial and maladaptive responses that ultimately yield a decrease in cardiac function. Despite these advancements, the prevalence of heart failure continues to rise and carries a significant burden on our patients and health care system...
July 2017: Current Treatment Options in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28512738/first-in-class-composite-angiotensin-receptor-neprilysin-inhibitors-arni-in-practice
#12
REVIEW
M H Barghash, A S Desai
Sacubitril/valsartan, a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI) inhibits angiotensin II and neprilysin, enhancing circulating vasoactive peptides. It is recommended in heart failure with reduced ejection fraction (HFrEF) as a result of the PARADIGM-HF trial.(1) This review discusses the rationale for neprilysin inhibition, data supporting efficacy, and practical tips for patient selection and utilization.
May 16, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28492561/-sacubitril-valsartan-a-new-and-effective-treatment-for-heart-failure-with-reduced-ejection-fraction
#13
Michele Senni, Bruno Trimarco, Michele Emdin, Luciano De Biase
Despite significant therapeutic advances, patients with chronic heart failure and reduced ejection fraction (HFrEF) remain at high risk for heart failure progression and death. The PARADIGM-HF study, the largest outcome trial in HFrEF, has shown improved cardiovascular outcomes with sacubitril/valsartan (Entresto®, Novartis), previously known as LCZ696, compared with angiotensin-converting enzyme (ACE) inhibitor therapy, possibly leading us to a new era for heart failure treatment. Sacubitril/valsartan represents a first-in-class drug acting through inhibition of angiotensin receptor and neprilysin, thus modulating the renin-angiotensin-aldosterone system and vasoactive substances such as natriuretic peptides...
January 2017: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/28489317/pharmacogenomics-of-angiotensin-receptor-neprilysin-inhibitor-and-its-long-term-side-effects
#14
REVIEW
Chayakrit Krittanawong, Takeshi Kitai
The development of the promising agent sacubitril/valsartan, known as an angiotensin receptor blocker-neprilysin inhibitor (ARNI), to improve heart failure (HF) management, may benefit morbidity, mortality, and readmission rates in patients with HF. The PARADIGM-HF trial demonstrated that the ARNI can reduce morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), while ongoing PARAMOUNT and PARAGON-HF trials determined whether the ARNI has morbidity and mortality benefits in patients with heart failure with preserved ejection fraction (HFpEF)...
May 10, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28483314/cardiovascular-and-diabetic-medications-that-cause-bradykinin-mediated-angioedema
#15
Stephanie N Hudey, Emma Westermann-Clark, Richard F Lockey
Medication-induced angioedema is a bradykinin-mediated process that results from increased production or decreased degradation of bradykinin. These reactions are documented for several cardiac medications including blockers of the renin-angiotensin-aldosterone system (RAAS). Other cardiovascular and diabetes medications further increase the risk of medication-induced angioedema, particularly with concomitant use of RAAS inhibitors. Dipeptidyl peptidase IV inhibitors are a class of oral diabetic agents that affect bradykinin and substance P degradation and therefore can lead to angioedema...
May 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28474543/neuroprotective-effects-of-citrus-fruit-derived-flavonoids-nobiletin-and-tangeretin-in-alzheimer-s-and-parkinson-s-disease
#16
Nady Braidy, Sahar Behzad, Solomon Habtemariam, Touqeer Ahmed, Maria Daglia, Seyed Mohammad Nabavi, Eduardo Sobarzo-Sanchez, Seyed Fazel Nabavi
Neurodegenerative diseases, namely Alzheimer`s disease and Parkinson's disease represent a deleterious impact worldwide. Despite extensive preclinical and clinical research in neurodegenerative disorders, therapeutic strategies aimed at the prevention and chronic treatment of neurodegenerative conditions have not been successfully translated to the clinic. Therefore, the identification of novel pharmacological intervention derived from natural products is warranted. Nobiletin and tangeretin are important citrus flavonoids derived from the peel and other parts of Citrus L...
March 27, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28466999/sarsasapogenin-aa13-ameliorates-a%C3%AE-induced-cognitive-deficits-via-improving-neuroglial-capacity-on-a%C3%AE-clearance-and-antiinflammation
#17
Cui Huang, Dong Dong, Qian Jiao, Hui Pan, Lei Ma, Rui Wang
AIMS: Sarsasapogenin has been reported to improve dementia symptoms somehow, probably through modulating the function of cholinergic system, suppressing neurofibrillary tangles, and inhibiting inflammation. However, the role of sarsasapogenin in response to beta-amyloid (Aβ) remains to be delineated. This study aimed to determine the therapeutic effect of sarsasapogenin-13 (AA13, a sarsasapogenin derivative) on learning and memory impairments in Aβ-injected mice, as well as the role of AA13 in neuroglia-mediated antiinflammation and Aβ clearance...
June 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28460827/heart-failure
#18
REVIEW
Marco Metra, John R Teerlink
Heart failure is common in adults, accounting for substantial morbidity and mortality worldwide. Its prevalence is increasing because of ageing of the population and improved treatment of acute cardiovascular events, despite the efficacy of many therapies for patients with heart failure with reduced ejection fraction, such as angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), β blockers, and mineralocorticoid receptor antagonists, and advanced device therapies. Combined angiotensin receptor blocker neprilysin inhibitors (ARNIs) have been associated with improvements in hospital admissions and mortality from heart failure compared with enalapril, and guidelines now recommend substitution of ACE inhibitors or ARBs with ARNIs in appropriate patients...
April 28, 2017: Lancet
https://www.readbyqxmd.com/read/28419972/neprilysin-inhibitors-a-new-hope-to-halt-the-diabetic-cardiovascular-and-renal-complications
#19
REVIEW
Vajir Malek, Anil Bhanudas Gaikwad
Diabetes is an enormous and ever-growing calamity and a global public health threat of the 21st century. Besides insulin and oral hypoglycaemic drugs, blockage of the renin-angiotensin system (RAS) denotes a key pharmacotherapy for the management of cardiovascular (CVD) and chronic kidney diseases (CKD), which are the leading causes of disability and death among diabetic patients. Neprilysin (NEP) inhibition, auxiliary to RAS blockage increases the bioavailability of natriuretic peptides and benefits the cardio-renal system...
June 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28417439/clinical-pharmacokinetics-of-sacubitril-valsartan-lcz696-a-novel-angiotensin-receptor-neprilysin-inhibitor
#20
REVIEW
Surya Ayalasomayajula, Thomas Langenickel, Parasar Pal, Sreedevi Boggarapu, Gangadhar Sunkara
Sacubitril/valsartan (LCZ696) is indicated for the treatment of heart failure with reduced ejection fraction. Absorption of sacubitril/valsartan and conversion of sacubitril (prodrug) to sacubitrilat (neprilysin inhibitor) was rapid with maximum plasma concentrations of sacubitril, sacubitrilat, and valsartan (angiotensin receptor blocker) reaching within 0.5, 1.5-2.0, and 2.0-3.0 h, respectively. With a two-fold increase in dose, an increase in the area under the plasma concentration-time curve was proportional for sacubitril, ~1...
April 17, 2017: Clinical Pharmacokinetics
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