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https://www.readbyqxmd.com/read/28419972/neprilysin-inhibitors-a-new-hope-to-halt-the-diabetic-cardiovascular-and-renal-complications
#1
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...
April 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28417439/clinical-pharmacokinetics-of-sacubitril-valsartan-lcz696-a-novel-angiotensin-receptor-neprilysin-inhibitor
#2
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
https://www.readbyqxmd.com/read/28398362/-the-relationship-between-natriuretic-peptides-and-neprilysin-pathways-the-clinical-simplification-against-the-complexity-of-biological-systems
#3
Giuseppe Di Tano, Aldo Clerico
A large body of evidence supports the use of natriuretic peptides (brain natriuretic peptide [BNP] and N-terminal proBNP [NT-proBNP]) for the evaluation and management of patients with heart failure over time. Elevated values reflect an enhanced counterregulatory response to hemodynamic stress and are indicative of heart failure severity, thus predicting prognosis. The clinical relevance and result interpretation of natriuretic peptides for monitoring therapy are still debated, and our understanding of their complex nature is still far from being complete...
February 2017: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/28392982/comparative-venom-gland-transcriptomics-of-naja-kaouthia-monocled-cobra-from-malaysia-and-thailand-elucidating-geographical-venom-variation-and-insights-into-sequence-novelty
#4
Kae Yi Tan, Choo Hock Tan, Lawan Chanhome, Nget Hong Tan
BACKGROUND: The monocled cobra (Naja kaouthia) is a medically important venomous snake in Southeast Asia. Its venom has been shown to vary geographically in relation to venom composition and neurotoxic activity, indicating vast diversity of the toxin genes within the species. To investigate the polygenic trait of the venom and its locale-specific variation, we profiled and compared the venom gland transcriptomes of N. kaouthia from Malaysia (NK-M) and Thailand (NK-T) applying next-generation sequencing (NGS) technology...
2017: PeerJ
https://www.readbyqxmd.com/read/28378286/resetting-the-neurohormonal-balance-in-heart-failure-hf-the-relevance-of-the-natriuretic-peptide-np-system-to-the-clinical-management-of-patients-with-hf
#5
REVIEW
Speranza Rubattu, Filippos Triposkiadis
The natriuretic peptide (NP) system, which includes atrial natriuretic peptide, B-type natriuretic peptide, and C-type natriuretic peptide, has an important role in cardiovascular homeostasis, promoting a number of physiological effects including diuresis, vasodilation, and inhibition of the renin-angiotensin-aldosterone system. Heart failure (HF) is associated with defects in NP processing and synthesis, and there is a strong relationship between NP levels and disease state. NPs are useful biomarkers in HF, and their use in diagnosis and evaluation of prognosis is well established, particularly in patients with HF with reduced ejection fraction (HFrEF)...
April 5, 2017: Heart Failure Reviews
https://www.readbyqxmd.com/read/28377431/the-renal-and-cardiovascular-effects-of-natriuretic-peptides
#6
Philip Ching Yat Wong, Jun Guo, Aidong Zhang
The landmark report by de Bold et al. in 1981 signified the heart as one of the endocrine organs involved in fluid and salt balance (de Bold AJ, Borenstein HB, Veress AT, Sonnenberg H. Life Sci 28: 89-94, 1981). Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are secreted from cardiomyocytes in response to cardiac stretch as in the case of heart failure, whereas C-type natriuretic peptide (CNP) is secreted from endothelial and renal cells in response to cytokines and endothelium-dependent agonists, such as acetylcholine...
June 1, 2017: Advances in Physiology Education
https://www.readbyqxmd.com/read/28371247/ivabradine-current-and-future-treatment-of-heart-failure
#7
Lene Thorup, Ulf Simonsen, Daniela Grimm, Elise Røge Hedegaard
In heart failure (HF), the heart cannot pump blood efficiently and is therefore unable to meet the body's demands of oxygen, and/or there is increased end diastolic pressure. Current treatments for heart failure with reduced ejection fraction (HFrEF) include angiotensin-converting enzyme (ACE)-inhibitors, angiotension receptor type 1 (AT1 ) antagonists, β-adrenoceptor-antagonists, aldosterone receptor antagonists, diuretics, digoxin and a combination drug with AT1 receptor antagonist and neprilysin inhibitor...
April 2, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28359417/early-adoption-of-sacubitril-valsartan-for-patients-with-heart-failure-with-reduced-ejection-fraction-insights-from-get-with-the-guidelines-heart-failure-gwtg-hf
#8
Nancy Luo, Gregg C Fonarow, Steven J Lippmann, Xiaojuan Mi, Paul A Heidenreich, Clyde W Yancy, Melissa A Greiner, Bradley G Hammill, N Chantelle Hardy, Stuart J Turner, Warren K Laskey, Lesley H Curtis, Adrian F Hernandez, Robert J Mentz, Emily C O'Brien
OBJECTIVES: The aim of this study was to assess the prevalence and variation in angiotensin receptor/neprilysin inhibitor (ARNI) prescription among a real-world population with heart failure with reduced ejection fraction (HFrEF). BACKGROUND: The U.S. Food and Drug Administration approved sacubitril/valsartan for patients with HFrEF in July 2015. Little is known about the early patterns of use of this novel therapy. METHODS: The study included patients discharged alive from hospitals in Get With the Guidelines-Heart Failure (GWTG-HF), a registry of hospitalized patients with heart failure, between July 2015 and June 2016 who had documentation of whether ARNIs were prescribed at discharge...
April 2017: JACC. Heart Failure
https://www.readbyqxmd.com/read/28358228/current-and-emerging-pharmacologic-options-for-the-management-of-patients-with-chronic-and-acute-decompensated-heart-failure
#9
Justyna Krzysztofik, Piotr Ponikowski
For many years heart failure (HF) was known as a fatal disease with an ominous prognosis. In the last decades better understanding of the pathophysiological mechanisms underlying HF has resulted in major breakthrough in the management and improvement in the natural history of this clinical syndrome. Areas covered: The review is focused on current and upcoming pharmacological therapies in patients with chronic and acute HF, starting with brief overview of drugs which improve the outcomes in patients with chronic HF with reduced ejection fraction (EF) including neurohormonal antagonists, angiotensin receptor neprilysin inhibitor and If- channel inhibitor, then presenting the summary of symptomatic treatment, the pharmacotherapy in chronic HF with preserved and mid-range EF and in acute HF...
May 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28338503/efficacy-and-safety-of-crystalline-valsartan-sacubitril-lcz696-compared-to-placebo-and-combinations-of-free-valsartan-and-sacubitril-in-patients-with-systolic-hypertension-the-ratio-study
#10
Joseph L Izzo, Dion H Zappe, Yan Jia, Kudsia Hafeez, Jack Zhang
We compared the systolic blood pressure-lowering efficacy and safety of crystalline valsartan/sacubitril (LCZ696, an angiotensin receptor blocker-neprilysin inhibitor) 400 mg daily against valsartan (320 mg once daily) alone or co-administered with placebo or increasing doses of free sacubitril (50, 100, 200, or 400 mg once daily) in order to identify the optimal antihypertensive combination dose. This multicenter, double-blinded, 7-arm parallel-group study recruited patients with mild-to-moderate systolic hypertension (office systolic BP 150-179 mmHg)...
March 23, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28333341/systemic-administration-of-sialorphin-attenuates-experimental-colitis-in-mice-via-interaction-with-mu-and-kappa-opioid-receptors
#11
M Salaga, A Mokrowiecka, D Jacenik, A I Cygankiewicz, E Malecka-Panas, R Kordek, W M Krajewska, M K Sobocinska, E Kamysz, J Fichna
Background and Aims: Pharmacological treatment and/or maintenance of remission in inflammatory bowel disease (IBD) is currently one of the biggest challenges in the field of gastroenterology. Here we aimed to assess the anti-inflammatory effect and the mechanism of action of sialorphin, the natural blocker of the endogenous opioid peptide-degrading enzymes neprilysin (NEP) and aminopeptidase N (APN), in the mouse models of IBD and the changes in the expression of these enzymes in IBD patients...
March 18, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28331987/hypertension-up-to-date-sprint-to-spyral
#12
REVIEW
Saarraaken Kulenthiran, Sebastian Ewen, Michael Böhm, Felix Mahfoud
Hypertension is the most common chronic cardiovascular condition with increasing prevalence all over the world. Treatment of patients at risk requires a multimodal therapeutic concept to adjust blood pressure, including systematic identification of secondary causes of hypertension or pseudo-resistance, lifestyle modification, polypharmacy, and as well as accompanying risk factors and comorbidities. The present review discusses recent studies on patients with increased cardiovascular risk potentially influencing future treatment strategies...
March 22, 2017: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://www.readbyqxmd.com/read/28330649/effect-of-sacubitril-valsartan-versus-enalapril-on-glycaemic-control-in-patients-with-heart-failure-and-diabetes-a-post-hoc-analysis-from-the-paradigm-hf-trial
#13
Jelena P Seferovic, Brian Claggett, Sara B Seidelmann, Ellen W Seely, Milton Packer, Michael R Zile, Jean L Rouleau, Karl Swedberg, Martin Lefkowitz, Victor C Shi, Akshay S Desai, John J V McMurray, Scott D Solomon
BACKGROUND: Diabetes is an independent risk factor for heart failure progression. Sacubitril/valsartan, a combination angiotensin receptor-neprilysin inhibitor, improves morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), compared with the angiotensin-converting enzyme inhibitor enalapril, and improves peripheral insulin sensitivity in obese hypertensive patients. We aimed to investigate the effect of sacubitril/valsartan versus enalapril on HbA1c and time to first-time initiation of insulin or oral antihyperglycaemic drugs in patients with diabetes and HFrEF...
March 17, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28326725/-analysis-of-salivary-protease-spectrum-in-chronic-periodontitis
#14
Li Qian, Zhou Xuedong, Fan Yaping, Yang Tengyu, Wu Songtao, Yu Yu, Chen Jiao, Zhang Ping, Feng Yun
OBJECTIVE: This study aimed to investigate the difference in salivary protease expression in patients with chronic periodontitis and normal individuals. METHODS: The stimulating saliva in patients with chronic periodontitis and normal individuals were collected. Protein chip technology was adapted to analyze salivary protease spectrum. RESULTS: Among the 34 proteases in the chip, disintegrin and metalloproteinase (ADAM)8, matrix metalloproteinase (MMP)-8, MMP-12, neprilysin/CD10, and uridylyl phosphate adenosine/urokinase showed a significantly increased concentration in the saliva of chronic periodontitis patients compared with those in the saliva of normal individuals (P<0...
February 1, 2017: Hua Xi Kou Qiang Yi Xue za Zhi, Huaxi Kouqiang Yixue Zazhi, West China Journal of Stomatology
https://www.readbyqxmd.com/read/28326642/neprilysin-inhibition-in-heart-failure-mechanisms-and-substrates-beyond-modulating-natriuretic-peptides
#15
REVIEW
Emilia D'Elia, Attilio Iacovoni, Muthiah Vaduganathan, Ferdinando L Lorini, Stefano Perlini, Michele Senni
The autonomic nervous system, the renin-angiotensin-aldosterone system, and the natriuretic peptide system represent critical regulatory pathways in heart failure and as such have been the major targets of pharmacological development. The introduction and approval of angiotensin receptor neprilysin inhibitors (ARNi) have broadened the available drug treatments of patients with chronic heart failure with reduced ejection fraction. Neprilysin catalyses the degradation of a number of vasodilator peptides, including the natriuretic peptides, bradykinin, substance P, and adrenomedullin, as well as vasoconstrictor peptides, including endothelin-1 and angiotensin I and II...
March 21, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28323997/degradation-paradigm-of-the-gut-hormone-pancreatic-polypeptide-by-hepatic-and-renal-peptidases
#16
Joyceline Cuenco, James Minnion, Tricia Tan, Rebecca Scott, Natacha Germain, Yiin Ling, Rong Chen, Mohammad Ghatei, Stephen Bloom
Pancreatic polypeptide (PP) is a gut hormone that acts on Y4 receptors to reduce appetite. Obese humans display a reduced postprandial rise in PP and remain fully sensitive to the anorectic effects of exogenous PP. The utility of PP as an antiobesity treatment is limited by its short circulating half-life. Insight into the mechanisms by which PP is degraded may aid design of long-acting PP analogues.We aimed to investigate the role of peptidases in PP degradation with a view to determining whether inhibition of these enzymes enhanced PP plasma levels and bioactivity in vivo...
March 9, 2017: Endocrinology
https://www.readbyqxmd.com/read/28322217/angiotensin-receptor-neprilysin-inhibitor-treatment-is-safe-and-potentially-efficacious-in-end%C3%A2-stage-hypertrophic-cardiomyopathy
#17
Paweł Rubiś
No abstract text is available yet for this article.
March 21, 2017: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/28318519/major-developments-in-the-2016-european-guidelines-for-heart-failure
#18
J C Trullàs, Á González-Franco
The European Society of Cardiology has recently published new guidelines on the diagnosis and treatment of acute and chronic heart failure (HF). This article aims to review these recommendations and their level of scientific evidence and to present the most innovative aspects. The most significant deviations from the 2012 edition are: 1) the introduction of the concept of HF with midrange LVEF (40-49%); 2) a new diagnostic algorithm for chronic HF, initially considering the clinical probability; 3) recommendations on preventing or delaying the apparition of HF; 4) indications for the use of the new sacubitril-valsartan compound, the first angiotensin receptor blocker and neprilysin inhibitor; 5) modification of indications for cardiac resynchronisation therapy; and 6) a new algorithm for a combined diagnostic and treatment strategy for acute HF based on the presence or absence of congestion and hypoperfusion...
March 15, 2017: Revista Clínica Española
https://www.readbyqxmd.com/read/28315356/the-effect-of-angiotensin-receptor-neprilysin-inhibitor-sacubitril-valsartan-on-central-nervous-system-amyloid-%C3%AE-concentrations-and-clearance-in-the-cynomolgus-monkey
#19
Heidi A Schoenfeld, Tim West, Philip B Verghese, Mary Holubasch, Neeta Shenoy, David Kagan, Chiara Buono, Wei Zhou, Marc DeCristofaro, Julie Douville, Geoffrey G Goodrich, Keith Mansfield, Chandra Saravanan, Frederic Cumin, Randy L Webb, Randall J Bateman
Sacubitril/valsartan (LCZ696) is the first angiotensin receptor neprilysin inhibitor approved to reduce cardiovascular mortality and hospitalization in patients with heart failure with reduced ejection fraction. As neprilysin (NEP) is one of several enzymes known to degrade amyloid-β (Aβ), there is a theoretical risk of Aβ accumulation following long-term NEP inhibition. The primary objective of this study was to evaluate the potential effects of sacubitril/valsartan on central nervous system clearance of Aβ isoforms in cynomolgus monkeys using the sensitive Stable Isotope Labeling Kinetics (SILK™)-Aβ methodology...
March 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28294061/the-association-of-mme-microrna-binding-site-polymorphism-with-risk-of-late-onset-alzheimer-s-disease-in-northern-han-chinese
#20
Chun-Xia Liu, Lin Tan, Fu-Rong Sun, Wei Zhang, Dan Miao, Meng-Shan Tan, Yu Wan, Chen-Chen Tan, Jin-Tai Yu, Lan Tan
Background Although amyloid β (Aβ) degradation has been normally implicated in the pathogenesis of late onset Alzheimer's disease (LOAD) through cellular biological studies, genetic studies linking Aβ degradation and LOAD are still not deeply investigated. Neprilysin (NEP), as one of the most crucial Aβ-degrading enzymes in AD, is the metalloendopeptidases which particularly participates in the monomeric Aβ species degradation. MicroRNAs (miRNAs) exert posttranscriptional dysregulation and their target sequence on the 3' untranslated regions (3'UTR) may be regulated by single nucleotide polymorphisms (SNPs)...
March 13, 2017: Current Neurovascular Research
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