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https://www.readbyqxmd.com/read/28333341/systemic-administration-of-sialorphin-attenuates-experimental-colitis-in-mice-via-interaction-with-mu-and-kappa-opioid-receptors
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
Paweł Rubiś
No abstract text is available yet for this article.
March 21, 2017: Pol Arch Intern Med
https://www.readbyqxmd.com/read/28318519/major-developments-in-the-2016-european-guidelines-for-heart-failure
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28290795/-a-breakthrough-in-the-treatment-of-patients-with-heart-failure-with-reduced-ejection-fraction-the-clinical-significance-of-the-paradigm-hf-trial
#11
Zh D Kobalava, S V Villevalde, O I Lukina
The implementation into clinical practice of new therapeutic strategies that could improve the prognosis of patients with heart failure (HF) with reduced ejection fraction (HFrEF) remains relevant. Innovative approach is to restore imbalances of neurohumoral systems by inhibiting angiotensin II receptor and neprilysin. The review presents the role of the natriuretic peptides system in the HFrEF pathophysiology, historical approaches to neurohormonal modulation, clinical pharmacology of the first in the class of angiotensin receptor and neprilysin inhibitor sakubitril/valsartan...
February 2017: Kardiologiia
https://www.readbyqxmd.com/read/28285126/expression-of-neprilysin-in-periodontitis-affected-gingival-tissues
#12
A Nezu, T Kubota, S Maruyama, M Nagata, K Nohno, T Morozumi, H Yoshie
OBJECTIVE: Although the pathogeneses of Alzheimer's disease (AD) and periodontal diseases have overlapping features, including ageing and chronic inflammation, the association between AD and periodontitis remains unclear. To explore the pathogenesis of periodontitis, a comprehensive gene expression/transcriptome analysis in periodontitis-affected gingival tissues found that the AD pathway was significantly up-regulated in periodontitis-affected gingival tissues. AD-related genes, amyloid beta precursor protein (APP), interleukin-1 beta and compliment 1QA, were significantly elevated in periodontitis...
March 6, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28285069/sacubitril-valsartan-the-newest-addition-to-the-toolbox-for-guideline-directed-medical-therapy-of-heart-failure
#13
REVIEW
Jo E Rodgers
Sacubitril/valsartan combines a neprilysin inhibitor with an angiotensin receptor blocker. As an inhibitor of neprilysin, an enzyme that degrade biologically active natriuretic peptides, this first-in-class therapy increases levels of circulating natriuretic peptides resulting in natriuretic, diuretic, and vasodilatory effects. In patients chronic New York Heart Association class II-IV heart failure with reduced ejection fraction, the PARADIGM-HF trial demonstrated that sacubitril/valsartan significantly reduced the primary endpoint of cardiovascular mortality and HF hospitalization compared to enalapril...
March 8, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28282805/humanin-specifically-interacts-with-amyloid-%C3%AE-oligomers-and-counteracts-their-in-vivo-toxicity
#14
Margherita Romeo, Matteo Stravalaci, Marten Beeg, Alessandro Rossi, Fabio Fiordaliso, Alessandro Corbelli, Mario Salmona, Marco Gobbi, Alfredo Cagnotto, Luisa Diomede
The 24-residue peptide humanin (HN) has been proposed as peptide-based inhibitors able to interact directly with amyloid-β (Aβ) oligomers and interfere with the formation and/or biological properties of toxic Aβ species. When administered exogenously HN, or its synthetic S14G-derivative (HNG), exerted multiple cytoprotective effects, counteracting the Aβ-induced toxicity. Whether these peptides interact directly with Aβ, particularly with the soluble oligomeric assemblies, remains largely unknown. We here investigated the ability of HN and HNG to interact directly with highly aggregating Aβ42, and interfere with the formation and toxicity of its oligomers...
March 6, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28282683/-indications-and-clinical-implications-of-the-use-of-the-cardiac-markers-bnp-and-nt-probnp
#15
Andreas Luchner, Stephan von Haehling, Christian Holubarsch, Till Keller, Fabian Knebel, Christian Zugck, Ulrich Laufs
B-type natriuretic peptides are markers of myocardial wall stress. BNP or NT-proBNP are used for the differential diagnosis of acute dyspnoe where normal serum concentrations make a cardiac cause unlikely. New data show their importance for risk prediction in different stages of heart failure and in primary prevention. Natriuretic peptide guided therapy improves titration of heart failure medications. Compared to BNP, NT-proBNP is better suited during therapy with the new angiotensin-rezeptor-neprilysin-inhibitor Sacubitril/Valsartan...
March 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28281174/potential-expanded-indications-for-neprilysin-inhibitors
#16
REVIEW
Elizabeth Riddell, Justin M Vader
PURPOSE OF REVIEW: The goal of this article is to review potential expanded indications for neprilysin inhibitors. This article reviews the rationale and design for ongoing and future trials of sacubitril/valsartan in cardiovascular and non-cardiovascular disease. RECENT FINDINGS: Randomized trial data are lacking for use of sacubitril/valsartan in acute heart failure and advanced heart failure. Mechanistic data from animal studies suggest a role for neprilysin inhibition in the treatment of post-myocardial infarction systolic dysfunction and heart failure with preserved ejection fraction...
April 2017: Current Heart Failure Reports
https://www.readbyqxmd.com/read/28266659/sequential-activation-of-different-pathway-networks-in-ischemia-affected-and-non-affected-myocardium-inducing-intrinsic-remote-conditioning-to-prevent-left-ventricular-remodeling
#17
Noemi Pavo, Dominika Lukovic, Katrin Zlabinger, Abelina Zimba, David Lorant, Georg Goliasch, Johannes Winkler, Dietmar Pils, Katharina Auer, Hendrik Jan Ankersmit, Zoltán Giricz, Tamas Baranyai, Márta Sárközy, András Jakab, Rita Garamvölgyi, Maximilian Y Emmert, Simon P Hoerstrup, Derek J Hausenloy, Péter Ferdinandy, Gerald Maurer, Mariann Gyöngyösi
We have analyzed the pathway networks of ischemia-affected and remote myocardial areas after repetitive ischemia/reperfusion (r-I/R) injury without ensuing myocardial infarction (MI) to elaborate a spatial- and chronologic model of cardioprotective gene networks to prevent left ventricular (LV) adverse remodeling. Domestic pigs underwent three cycles of 10/10 min r-I/R by percutaneous intracoronary balloon inflation/deflation in the mid left anterior descending artery, without consecutive MI. Sham interventions (n = 8) served as controls...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28250274/neprilysin-is-suppressed-by-dual-specificity-tyrosine-phosphorylation-regulated-kinase-1a-dyrk1a-in-down-syndrome-derived-fibroblasts
#18
Takashi Kawakubo, Ryotaro Mori, Keiro Shirotani, Nobuhisa Iwata, Masashi Asai
Amyloid-β peptide (Aβ) accumulation is a triggering event leading to the Alzheimer's disease (AD) pathological cascade. Almost all familial AD-linked gene mutations increase Aβ production and accelerate the onset of AD. The Swedish mutation of amyloid precursor protein (APP) affects β-secretase activity and increases Aβ production up to ca. 6-fold in cultured cells; the onset age is around 50. Down syndrome (DS) patients with chromosome 21 trisomy present AD-like pathologies at earlier ages (40s) compared with sporadic AD patients, because APP gene expression is 1...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28248903/is-there-a-place-for-a-dual-angiotensin-receptor-neprilysin-inhibitor-in-the-treatment-of-hypertension
#19
Michel Burnier
No abstract text is available yet for this article.
April 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28244205/what-proportion-of-patients-with-chronic-heart-failure-are-eligible-for-sacubitril-valsartan
#20
Pierpaolo Pellicori, Alessia Urbinati, Parin Shah, Alexandra MacNamara, Syed Kazmi, Riet Dierckx, Jufen Zhang, John G F Cleland, Andrew L Clark
AIMS: The PARADIGM-HF trial showed that sacubitril-valsartan, an ARB-neprilysin inhibitor, is more effective than enalapril for some patients with heart failure (HF). It is uncertain what proportion of patients with HF would be eligible for sacubitril-valsartan in clinical practice. METHODS AND RESULTS: Between 2001 and 2014, 6131 patients consecutively referred to a community HF clinic with suspected HF were assessed. The criteria required to enter the randomized phase of PARADIGM-HF, including symptoms, NT-proBNP, and current treatment with or without target doses of ACE inhibitors or ARBs, were applied to identify the proportion of patients eligible for sacubitril-valsartan...
February 27, 2017: European Journal of Heart Failure
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