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https://www.readbyqxmd.com/read/28809748/new-issues-on-measurement-of-b-type-natriuretic-peptides
#1
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
#2
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
#3
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
#4
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
https://www.readbyqxmd.com/read/28765411/heart-failure-what-s-new-and-what-s-changed
#5
Paul D Callan, Andrew L Clark
Physicians responsible for the care of patients with heart failure due to left ventricular systolic dysfunction have access to a broad range of evidence-based treatments that prolong life and reduce symptoms. In spite of the significant progress made over the last four decades, there is an ongoing need for novel therapies to treat a condition that is associated with stubbornly high morbidity and mortality. In this article, we discuss the findings of SERVE-HF, a randomised controlled trial of adaptive servo-ventilation in patients with left ventricular systolic dysfunction, as well as EMPA-REG, a study of the effects of a novel diabetic agent that may be of greater interest to heart failure specialists than diabetologists...
July 2017: Clinical Medicine: Journal of the Royal College of Physicians of London
https://www.readbyqxmd.com/read/28743230/cart-modulates-beta-amyloid-metabolism-associated-enzymes-and-attenuates-memory-deficits-in-app-ps1-mice
#6
Kailin Yin, Jiali Jin, Xiaolei Zhu, Linjie Yu, Sulei Wang, Lai Qian, Lijuan Han, Yun Xu
INTRODUCTION: Cocaine- and amphetamine-regulated transcript (CART) peptide has been demonstrated to exert neuroprotective effects in stroke and some neurodegeneration diseases. In current study, we investigated the protective effects and underlying mechanisms of CART in APP/PS1 mice. METHODS: The protein levels of CART, soluble Aβ1-40 and Aβ1-42 were measured in the hippocampus of APP/PS1 mice by enzyme-linked immunosorbent assay. We determined the mRNA and protein levels of Aβ metabolism-associated enzymes including neprilysin (NEP), insulin-degrading enzyme (IDE), receptor for advanced glycation end products (RAGE), and low-density lipoprotein receptor-related protein 1 (LRP-1) in the hippocampus of APP/PS1 mice using real-time PCR and western blotting...
July 25, 2017: Neurological Research
https://www.readbyqxmd.com/read/28735360/navigating-the-future-of-cardiovascular-drug-development-leveraging-novel-approaches-to-drive-innovation-and-drug-discovery-summary-of-findings-from-the-novel-cardiovascular-therapeutics-conference
#7
REVIEW
Thomas J Povsic, Rob Scott, Kenneth W Mahaffey, Robert Blaustein, Jay M Edelberg, Martin P Lefkowitz, Scott D Solomon, Jonathan C Fox, Kevin E Healy, Aarif Y Khakoo, Douglas W Losordo, Fady I Malik, Brett P Monia, Rusty L Montgomery, Jeffrey Riesmeyer, Gregory G Schwartz, Steven L Zelenkofske, Joseph C Wu, Scott M Wasserman, Matthew T Roe
PURPOSE: The need for novel approaches to cardiovascular drug development served as the impetus to convene an open meeting of experts from the pharmaceutical industry and academia to assess the challenges and develop solutions for drug discovery in cardiovascular disease. METHODS: The Novel Cardiovascular Therapeutics Summit first reviewed recent examples of ongoing or recently completed programs translating basic science observations to targeted drug development, highlighting successes (protein convertase sutilisin/kexin type 9 [PCSK9] and neprilysin inhibition) and targets still under evaluation (cholesteryl ester transfer protein [CETP] inhibition), with the hope of gleaning key lessons to successful drug development in the current era...
July 22, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28720639/angioedema-spotlight-a-closer-examination-of-sacubitril-valsartan-safety-results
#8
Ryan E Owens, Carrie S Oliphant
Incorporation of neprilysin inhibition into heart failure pharmacotherapy regimens has recently been recommended by U.S. guidelines, based on results from the PARADIGM-HF trial comparing sacubitril/valsartan to enalapril. While most of the discussion has focused on efficacy, a closer examination of the safety results, particularly the incidence of angioedema during the run-in and double-blind periods, is also warranted. Although no major safety concerns were identified, an angioedema risk comparable to enalapril was found, primarily in the black population...
July 2017: Journal of the American Board of Family Medicine: JABFM
https://www.readbyqxmd.com/read/28719622/characterization-of-plasma-metal-profiles-in-alzheimer-s-disease-using-multivariate-statistical-analysis
#9
Chunmei Guan, Rui Dang, Yu Cui, Liyan Liu, Xiaobei Chen, Xiaoyu Wang, Jingli Zhu, Donggang Li, Junwei Li, Decai Wang
The exact cause of Alzheimer's disease (AD) and the role of metals in its etiology remain unclear. We have used an analytical approach, based on inductively coupled plasma mass spectrometry coupled with multivariate statistical analysis, to study the profiles of a wide range of metals in AD patients and healthy controls. AD cannot be cured and the lack of sensitive biomarkers that can be used in the early stages of the disease may contribute to this treatment failure. In the present study, we measured plasma levels of amyloid-β1-42(0...
2017: PloS One
https://www.readbyqxmd.com/read/28714615/-arni-new-abbreviation-for-a-new-class-of-treatment-of-heart-failure
#10
Soran Karimzadeh, Hazrije Mustafić, Tomoe Stampfli Andres
ARNI (Angiontensin Receptor Neprilysin Inhibitor) are a new class of drug : the angiotensin and neprilysin inhibitors. This combined effect allows an optimisation of the heart failure treatment by acting on both pathways of the renin-angiotensin-aldosterone and of the natriuretic peptides. LCZ696 is a combined molecule of valsartan and sacubitril and is currently the only one on the market. Its efficacy has been shown in a large randomised trial in 2014, and LCZ696 is now part of the last 2016 European Society of Cardiology guidelines for the management of heart failure...
March 1, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28697571/psd-93-attenuates-amyloid-%C3%AE-mediated-cognitive-dysfunction-by-promoting-the-catabolism-of-amyloid-%C3%AE
#11
Linjie Yu, Yi Liu, Hui Yang, Xiaolei Zhu, Xiang Cao, Jun Gao, Hui Zhao, Yun Xu
Amyloid-β (Aβ) is a key neuropathological hallmark of Alzheimer's disease (AD). Postsynaptic density protein 93 (PSD-93) is a key scaffolding protein enriched at postsynaptic sites. The aim of the present study was to examine whether PSD-93 overexpression could alleviate Aβ-induced cognitive dysfunction in APPswe/PS1dE9 (APP/PS1) mice by reducing Aβ levels in the brain. The level of PSD-93 was significantly decreased in the hippocampus of 6-month-old APP/PS1 mice compared with that in wild-type mice. Following lentivirus-mediated PSD-93 overexpression, cognitive function, synaptic function, and amyloid burden were investigated...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28689178/sacubitril-valsartan-beyond-natriuretic-peptides
#12
REVIEW
Jagdeep S S Singh, Louise M Burrell, Myriam Cherif, Iain B Squire, Andrew L Clark, Chim C Lang
Natriuretic peptides, especially B-type natriuretic peptide (BNP), have primarily been regarded as biomarkers in heart failure (HF). However, they are also possible therapeutic agents due to their potentially beneficial physiological effects. The angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan, simultaneously augments the natriuretic peptide system (NPS) by inhibiting the enzyme neprilysin (NEP) and inhibits the renin-angiotensin-aldosterone system (RAAS) by blocking the angiotensin II receptor...
July 8, 2017: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/28685579/synthetic-modification-within-the-rprl-region-of-apelin-peptides-impact-on-cardiovascular-activity-and-stability-to-neprilysin-and-plasma-degradation
#13
Shaun M K McKinnie, Wang Wang, Conrad Fischer, Tyler McDonald, Kevin R Kalin, Xavier Iturrioz, Catherine Llorens-Cortes, Gavin Y Oudit, John C Vederas
Apelin is an important mammalian peptide hormone with a range of physiological roles, especially in the cardiovascular system. The apelinergic system is a promising target for treatment of disease, but this remains to be realized due to rapid proteolysis of apelin-derived peptides by proteases, including neprilysin (NEP). The synthetic analogues modified within the NEP degradation site ("RPRL" motif) showed improved in vitro proteolytic stability while maintaining receptor-binding affinities, with three candidate peptides retaining full cardiovascular activities for potential therapeutic application...
July 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28676269/substituted-%C3%AE-mercaptoketones-new-types-of-specific-neprilysin-inhibitors
#14
Hervé Poras, Rémi Patouret, Simon Leiris, Tanja Ouimet, Marie-Claude Fournié-Zaluski, Bernard P Roques
New neprilysin inhibitors containing an α-mercaptoketone HSC(R(1)R(2))CO group, as zinc ligand were designed. Two parameters were explored for potency optimization: the size of the inhibitor which could interact with the S1, S1' or S2' domain of the enzyme and the nature of the substituents R(1), R(2) of the mercaptoketone group. Introduction of a cyclohexyl chain in R(1), R(2) position and a (3-thiophen)benzyl group in position R(3) (compound 12n) yielded to the most potent inhibitor of this series with a Ki value of 2±0...
June 21, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28676030/heart-failure-with-preserved-ejection-fraction-a-dilemma-in-treatment-options
#15
Taylor Bramblett, Mohamed Teleb, Aymen Albaghdadi, Harsh Agrawal, Debabrata Mukherjee
Heart failure with preserved ejection fraction (HFpEF) makes up half of diagnosed heart failure cases and has similar outcomes compared to heart failure with reduced ejection fraction (HFrEF) but a discrepancy in knowledge and approach to treatment. HFpEF is diagnosed using the following criteria: symptoms, preserved ejection fraction (greater than 50%), and evidence of abnormal left ventricular filling or relaxation, or diastolic distensibility or stiffness. Studies conducted to examine the efficacy of angiotensin receptor blockers (irbesartan and candesartan), thiazide diuretics (chlorthalidone), and angiotensin converting enzyme inhibitors (perindopril) in the treatment of HFpEF, showed moderate efficacy but no clear benefit...
July 3, 2017: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/28674290/elucidating-pathogenic-mechanisms-of-early-onset-alzheimer-s-disease-in-down-syndrome-patients
#16
Masashi Asai, Takashi Kawakubo, Ryotaro Mori, Nobuhisa Iwata
 Down syndrome (DS) patients demonstrate the neuropathology of Alzheimer's disease (AD) characterized by the formation of senile plaques and neurofibrillary tangles by age 40-50 years. It has been considered for a number of years that 1.5-fold expression of the gene for the amyloid precursor protein (APP) located on chromosome 21 leading to overproduction of amyloid-β peptide (Aβ) results in the early onset of AD in adults with DS. However, the mean age of onset of familial AD with the Swedish mutation on APP which has high affinity for β-secretase associated with a dramatic increase in Aβ production is about 55 years...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28662936/angiotensin-receptor-neprilysin-inhibition%C3%A2-in-heart-failure-with-preserved%C3%A2-ejection-fraction-rationale-and-design-of-the-paragon-hf-trial
#17
REVIEW
Scott D Solomon, Adel R Rizkala, Jianjian Gong, Wenyan Wang, Inder S Anand, Junbo Ge, Carolyn S P Lam, Aldo P Maggioni, Felipe Martinez, Milton Packer, Marc A Pfeffer, Burkert Pieske, Margaret M Redfield, Jean L Rouleau, Dirk J Van Veldhuisen, Faiez Zannad, Michael R Zile, Akshay S Desai, Victor C Shi, Martin P Lefkowitz, John J V McMurray
OBJECTIVES: The PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction) trial is designed to determine the efficacy and safety of the angiotensin receptor neprilysin inhibitor sacubitril/valsartan compared with valsartan in patients with chronic heart failure and preserved ejection fraction (HFpEF). BACKGROUND: HFpEF is highly prevalent, associated with substantial morbidity and mortality, and in need of effective therapies that improve outcomes...
July 2017: JACC. Heart Failure
https://www.readbyqxmd.com/read/28656517/treatment-of-hyperkalemia-in-heart-failure
#18
REVIEW
Ersilia M DeFilippis, Akshay S Desai
PURPOSE OF REVIEW: The aim of this paper is to discuss strategies for prevention and management of hyperkalemia in patients with heart failure, including the role of novel therapies. RECENT FINDINGS: Renin-angiotensin-aldosterone system (RAAS) antagonists, including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), and mineralocorticoid receptor antagonists (MRA) decrease mortality and morbidity in heart failure but increase the risk of hyperkalemia, especially when used in combination...
August 2017: Current Heart Failure Reports
https://www.readbyqxmd.com/read/28653148/-new-pharmacologic-therapies-for-chronic-heart-failure
#19
REVIEW
T Kempf, U Bavendiek, J Bauersachs
Heart failure is a disease with a high prevalence and incidence. New therapeutic approaches are needed to prevent the onset of heart failure and to reduce the high morbidity and mortality associated with this disease. An optimized therapy of arterial hypertension in patients with risk factors and the use of the SGLT2 inhibitor empagliflozin in type 2 diabetics are proven strategies to prevent heart failure. The therapeutic options in heart failure with preserved ejection fraction are still insufficient. In heart failure with reduced ejection fraction sacubitril/valsartan, the first approved angiotensin receptor-neprilysin inhibitor, is superior to an angiotensin converting enzyme (ACE) inhibitor...
June 26, 2017: Der Internist
https://www.readbyqxmd.com/read/28652105/pharmacokinetic-pharmacodynamic-and-antihypertensive-effects-of-the-neprilysin-inhibitor-lcz-696-sacubitril-valsartan
#20
REVIEW
Steven G Chrysant
LCZ-696, sacubitril/valsartan, is a dual-acting molecule consisting of the angiotensin II (Ang II) receptor blocker valsartan and the neprilysin (neutral endopeptidase) inhibitor AHU-377 with significant beneficial effects in patients with hypertension and heart failure (HF). Several recent studies have demonstrated a higher effectiveness of LCZ-696 compared to valsartan in the treatment of hypertension and HF. The rationale for the development and the Food and Drug Administration approval of LCZ-696 was based on the concept of an additive effect of the Ang II receptor blocker valsartan and the neutral endopeptidase (neprilysin) inhibitor AHU-377 for the treatment of hypertension and HF...
July 2017: Journal of the American Society of Hypertension: JASH
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