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https://www.readbyqxmd.com/read/28527109/erratum-to-clinical-pharmacokinetics-of-sacubitril-valsartan-lcz696-a-novel-angiotensin-receptor-neprilysin-inhibitor
#1
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/28525892/rasal1-is-a-potent-regulator-of-hepatic-stellate-cell-activity-and-liver-fibrosis
#2
Akemi Takata, Motoyuki Otsuka, Takahiro Kishikawa, Mari Yamagami, Rei Ishibashi, Kazuma Sekiba, Tatsunori Suzuki, Motoko Ohno, Yui Yamashita, Takaya Abe, Ryota Masuzaki, Tsuneo Ikenoue, Kazuhiko Koike
Liver fibrosis, leading to cirrhosis and liver failure, can occur after chronic liver injury. The transition of hepatic stellate cells (HSCs) from quiescent cells into proliferative and fibrogenic cells is a central event in liver fibrosis. Here, we show that RAS protein activator like-1 (RASAL1), a RAS-GTPase-activating protein, which switches off RAS activity, is significantly decreased during HSC activation, and that HSC activation can be antagonized by forced expression of the RASAL1 protein. We demonstrate that RASAL1 suppresses HSC proliferation by regulating the Ras-MAPK pathway, and that RASAL1 suppresses HSC fibrogenic activity by regulating the PKA-LKB1-AMPK-SRF pathway by interacting with angiotensin II receptor, type 1...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28509128/a-case-of-rapid-amelioration-of-hepatitis-c-virus-associated-cryoglobulinemic-membranoproliferative-glomerulonephritis-treated-by-interferon-free-directly-acting-antivirals-for-hcv-in-the-absence-of-immunosuppressant
#3
Fumiaki Obata, Taichi Murakami, Junko Miyagi, Sayo Ueda, Taizo Inagaki, Masanori Minato, Hiroyuki Ono, Kenji Nishimura, Eriko Shibata, Masanori Tamaki, Sakiya Yoshimoto, Fumi Kishi, Seiji Kishi, Motokazu Matsuura, Kojiro Nagai, Hideharu Abe, Toshio Doi
Mixed cryoglobulinemic syndrome, which is a systemic vasculitis characterized by the immune complex deposition in small- and medium-sized arteries and most often due to chronic hepatitis C virus (HCV) infection, sometimes clinically manifests as refractory glomerulonephritis or nephritic syndrome. Patients with mixed cryoglobulinemic nephropathy who have a rapidly progressive glomerulonephritis should receive immunosuppressive therapy. After disease stabilization, patients should receive concurrent therapy for the underlying HCV infection...
May 2017: CEN Case Reports
https://www.readbyqxmd.com/read/28505074/nafld-and-atherosclerosis-are-prevented-by-a-natural-dietary-supplement-containing-curcumin-silymarin-guggul-chlorogenic-acid-and-inulin-in-mice-fed-a-high-fat-diet
#4
Antonella Amato, Gaetano-Felice Caldara, Domenico Nuzzo, Sara Baldassano, Pasquale Picone, Manfredi Rizzo, Flavia Mulè, Marta Di Carlo
Non-alcoholic fatty liver disease (NAFLD) confers an increased risk of cardiovascular diseases. NAFDL is associated with atherogenic dyslipidemia, inflammation and renin-angiotensin system (RAS) imbalance, which in turn lead to atherosclerotic lesions. In the present study, the impact of a natural dietary supplement (NDS) containing Curcuma longa, silymarin, guggul, chlorogenic acid and inulin on NAFLD and atherosclerosis was evaluated, and the mechanism of action was examined. C57BL/6 mice were fed an HFD for 16 weeks; half of the mice were simultaneously treated with a daily oral administration (os) of the NDS...
May 13, 2017: Nutrients
https://www.readbyqxmd.com/read/28484393/the-role-of-the-apelin-apj-system-in-the-regulation-of-liver-disease
#5
REVIEW
Xinrui Lv, Jing Kong, Wei-Dong Chen, Yan-Dong Wang
Apelin is an endogenous peptide that is a ligand for the APJ receptor (angiotensin II receptor like-1, AT-1). The apelin/APJ system is distributed in diverse periphery organ tissues. It has been shown that the apelin/APJ system plays various roles in physiology and pathophysiology of many organs. It regulates cardiovascular development or cardiac disease, glycometabolism and fat metabolism as well as metabolic disease. The apelin/APJ system participates in various cell activities such as proliferation, migration, apoptosis or inflammation...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28467442/the-transcriptional-regulation-of-the-human-angiotensinogen-gene-after-high-fat-diet-is-haplotype-dependent-novel-insights-into-the-gene-regulatory-networks-and-implications-for-human-hypertension
#6
Anita Rana, Sudhir Jain, Nitin Puri, Meenakshi Kaw, Natalie Sirianni, Deniz Eren, Brahma Raju Mopidevi, Ashok Kumar
Single nucleotide polymorphisms (SNPs) in the human angiotensinogen (hAGT) gene may modulate its transcription and affect the regulation of blood pressure via activation of the renin-angiotensin aldosterone system (RAAS). In this regard, we have identified polymorphisms in the 2.5 Kb promoter of the hAGT gene that form two haplotype (Hap) blocks: -6A/G (-1670A/G, -1562C/T, -1561T/C) and -217A/G (-532T/C, -793A/G, -1074T/C & -1178G/A). hAGT gene with Hap -6A/-217A (Hap I) is associated with increased blood pressure whereas, Hap -6G/-217G (Hap II) is associated with normal blood pressure in human subjects...
2017: PloS One
https://www.readbyqxmd.com/read/28438644/long-term-effects-of-angiotensin-1-7-on-lipid-metabolism-in-the-adipose-tissue-and-liver
#7
Carolina Campos Lima Moreira, Fabíola Cesário Lourenço, Érica Guilhen Mario, Robson Augusto Souza Santos, Leida Maria Botion, Valéria Ernestânia Chaves
The angiotensin (Ang) converting enzyme 2/Ang-(1-7)/Mas axis has been described to have a beneficial role on metabolic disorders. In the present study, the use of a transgenic rat model that chronically overexpresses Ang-(1-7) enabled us to investigate the chronic effects of this peptide on lipid accumulation in the liver and adipose tissue. The transgenic group showed a marked tendency toward increased expression of peroxisome proliferator-activated receptor-γ (PPARγ) and decreased lipoprotein lipase (LPL) expression and activity in epididymal adipose tissue...
April 22, 2017: Peptides
https://www.readbyqxmd.com/read/28437842/autoimmune-like-chronic-hepatitis-induced-by-olmesartan
#8
Sandrine Barge, Marianne Ziol, Jean-Charles Nault
Drug liver-induced injury (DILI) due to minocyclin, alpha methyldopa or nitrofurantoin may be responsible for chronic liver damage that mimic the biological and/or histological features of chronic autoimmune hepatitis and, in rare cases, progresses to cirrhosis(1). Olmesartan medoxomil is an antihypertensive drug that acts by blocking the angiotensin II receptor and is metabolized into its pharmacologically active form, olmesartan, in the intestine and in the liver before being released into the systemic circulation...
April 24, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28421320/hepatocyte-specific-depletion-of-ubiquitin-regulatory-x-domain-containing-protein-8-accelerates-fibrosis-in-a-mouse-non-alcoholic-steatohepatitis-model
#9
Norihiro Imai, Michitaka Suzuki, Yoji Ishizu, Teiji Kuzuya, Takashi Honda, Kazuhiko Hayashi, Masatoshi Ishigami, Yoshiki Hirooka, Tetsuya Ishikawa, Hidemi Goto, Toyoshi Fujimoto
Ubiquitin regulatory X domain-containing protein 8 (UBXD8) is engaged in the degradation of lipidated apolipoprotein B in hepatocytes. We previously showed that hepatocyte-specific UBXD8-deficient mice (U8-HKO) fed a moderately high-fat diet (31 kcal % fat) showed periportal macrovesicular steatosis along with a decrease in very low-density lipoprotein secretion, but did not develop fibrosis. In the present study, we examined whether U8-HKO mice show NASH-like phenotypes when fed a very high-fat diet (60 kcal % fat)...
April 18, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28417439/clinical-pharmacokinetics-of-sacubitril-valsartan-lcz696-a-novel-angiotensin-receptor-neprilysin-inhibitor
#10
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/28414295/high-salt-intake-reprioritizes-osmolyte-and-energy-metabolism-for-body-fluid-conservation
#11
Kento Kitada, Steffen Daub, Yahua Zhang, Janet D Klein, Daisuke Nakano, Tetyana Pedchenko, Louise Lantier, Lauren M LaRocque, Adriana Marton, Patrick Neubert, Agnes Schröder, Natalia Rakova, Jonathan Jantsch, Anna E Dikalova, Sergey I Dikalov, David G Harrison, Dominik N Müller, Akira Nishiyama, Manfred Rauh, Raymond C Harris, Friedrich C Luft, David H Wassermann, Jeff M Sands, Jens Titze
Natriuretic regulation of extracellular fluid volume homeostasis includes suppression of the renin-angiotensin-aldosterone system, pressure natriuresis, and reduced renal nerve activity, actions that concomitantly increase urinary Na+ excretion and lead to increased urine volume. The resulting natriuresis-driven diuretic water loss is assumed to control the extracellular volume. Here, we have demonstrated that urine concentration, and therefore regulation of water conservation, is an important control system for urine formation and extracellular volume homeostasis in mice and humans across various levels of salt intake...
May 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28356040/the-relevance-of-dietary-polyphenols-in-cardiovascular-protection
#12
Ana Gabriela Murillo, Maria Luz Fernandez
The chemical structure of polyphenols consisting of aromatic rings, capable of quenching free radicals, makes them ideal candidates to protect against oxidation. Polyphenols are present in a variety of foods including grapes, berries, dark chocolate, coffee and tea to mention a few. A number of studies have shown that dietary polyphenols exert a protective effect against hypertension, dyslipidemias, inflammation, endothelial function and atherosclerosis, conditions associated with increased risk for cardiovascular disease...
March 29, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28330766/water-metabolism-dysfunction-via-renin-angiotensin-system-activation-caused-by-liver-damage-in-mice-treated-with-microcystin-rr
#13
Qing Zhong, Feng Sun, Weiguang Wang, Wenqing Xiao, Xiaoni Zhao, Kangding Gu
Microcystins (MCs) are a group of monocyclic heptapeptide toxins that have been shown to act as potent hepatotoxins. However, the observed symptoms of water metabolism disruption induced by microcystin-RR (MC-RR) or MCs have rarely been reported, and a relatively clear mechanism has not been identified. In the present study, male mice were divided into 4 groups (A: 140μg/kg, B: 70μg/kg,C: 35μg/kg, and D: 0μg/kg) and administered MC-RR daily for a month. On day 8 of treatment, an increase in water intake and urine output was observed in the high-dose group compared with the control, and the symptoms worsened with the repeated administration of the toxin until day 30...
May 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28290069/significance-of-genetic-polymorphisms-in-patients-with-nonalcoholic-fatty-liver-disease
#14
REVIEW
Hisamitsu Miyaaki, Kazuhiko Nakao
Because of recent advances in genetic research such as genome-wide association studies, the underlying genetic mechanisms of nonalcoholic fatty liver disease (NAFLD) pathophysiology have been elucidated. Here, we present a review of the current literature on the impact of genetic polymorphisms in patients with NAFLD. These genetic polymorphisms, which regulate lipid metabolism, glucose metabolism, and the renin-angiotensin system, are involved in NAFLD onset, steatosis, inflammation, fibrosis, and hepatocellular carcinoma (HCC)...
June 2017: Clinical Journal of Gastroenterology
https://www.readbyqxmd.com/read/28285069/sacubitril-valsartan-the-newest-addition-to-the-toolbox-for-guideline-directed-medical-therapy-of-heart-failure
#15
REVIEW
Jo E Rodgers
Sacubitril/valsartan combines a neprilysin inhibitor with an angiotensin receptor blocker. As an inhibitor of neprilysin, an enzyme that degrades biologically active natriuretic peptides, this first-in-class therapy increases levels of circulating natriuretic peptides, resulting in natriuretic, diuretic, and vasodilatory effects. In patients with 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 heart failure hospitalization, compared with enalapril...
March 9, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28283858/combination-therapy-with-lamivudine-and-angiotensin-converting-enzyme-inhibitor-angiotensin-receptor-blocker-for-hepatitis-b-virus-associated-glomerulonephritis-with-mild-to-moderate-proteinuria-a-clinical-review-of-38-cases
#16
Li-Jing Sun, Jian-Ping Shan, Ruo-Lan Cui, Wei-Jie Yuan, Geng-Ru Jiang
PURPOSE: The treatment of HBV-associated glomerulonephritis (HBV-GN) is still a challenge in clinical practice now. The objective of this study was to report the pathological characteristics of HBV-GN presenting with mild to moderate proteinuria and to evaluate the therapeutic efficacy of lamivudine (LAM) in combination with angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) as compared to ACEI/ARB monotherapy. METHODS: We conducted a retrospective observational study in HBV-GN patients between 2005 and 2014...
March 10, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28263289/establishment-of-a-mouse-model-of-enalapril-induced-liver-injury-and-investigation-of-the-pathogenesis
#17
Yuji Shirai, Shingo Oda, Sayaka Makino, Koichi Tsuneyama, Tsuyoshi Yokoi
Drug-induced liver injury (DILI) is a major concern in drug development and clinical drug therapy. Since the underlying mechanisms of DILI have not been fully understood in most cases, elucidation of the hepatotoxic mechanisms of drugs is expected. Although enalapril (ELP), an angiotensin-converting enzyme inhibitor, has been reported to cause liver injuries with a low incidence in humans, the precise mechanisms by which ELP causes liver injury remains unknown. In this study, we established a mouse model of ELP-induced liver injury and analyzed the mechanisms of its hepatotoxicity...
March 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28207324/is-serum-angiotensin-converting-enzyme-level-useful-for-determining-necroinflammatory-activity-in-chronic-hepatitis-b-infection
#18
Ahmet Tay, Fatih Albayrak, Sevilay Ozmen, Ayse Albayrak, Kemalettin Ozden
AIM: The purpose of this study was to investigate the relationship between the findings from liver biopsy and the serum angiotensin-converting enzyme (ACE) level to determine whether ACE might serve as a potential noninvasive sign of necroinflammatory activity in patients with Chronic Hepatitis B (CHB) infection. METHODS: A total of 54 CHB patients referred for liver biopsy were enrolled in the study. Serum ACE levels were determined photometrically with a kinetic test...
February 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28164519/angiotensin-converting-enzyme-inhibitors-influence-on-antiplatelet-therapy-of-clopidogrel-in-acs
#19
Shuo Yang, Chanjuan Cui, Jie Zhang, Rui Qiao
BACKGROUND: Clopidogrel is a prodrug, the minority of which is converted to an active metabolite by hepatic cytochrome P450 (CYP2C19), however, most of it is metabolized to inactive substance by hepatic carboxylesterase1 (CES1). Meanwhile angiotensin-converting enzyme inhibitors (ACEIs) are mostly metabolized by CES1. We aimed to assess the impact of ACEIs on platelet inhibition by clopidogrel. METHODS: We genotyped variants CES1, CYP2C19*2 and *3 in 502 patients with acute coronary syndrome (ACS) receiving clopidogrel therapy, and analyzed the effects of ACEIs on responsiveness to clopidogrel by the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay and ADP-stimulated impedance whole blood platelet aggregation assay...
October 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28144388/hepatic-structural-enhancement-and-insulin-resistance-amelioration-due-to-at1-receptor-blockade
#20
EDITORIAL
Vanessa Souza-Mello
Over the last decade, the role of renin-angiotensin system (RAS) on the development of obesity and its comorbidities has been extensively addressed. Both circulating and local RAS components are up-regulated in obesity and involved in non-alcoholic fatty liver disease onset. Pharmacological manipulations of RAS are viable strategies to tackle metabolic impairments caused by the excessive body fat mass. Renin inhibitors rescue insulin resistance, but do not have marked effects on hepatic steatosis. However, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ARB) yield beneficial hepatic remodeling...
January 18, 2017: World Journal of Hepatology
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