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https://www.readbyqxmd.com/read/29772435/aliskiren-preclinical-evidence-for-the-treatment-of-hyperproliferative-skin-disorders
#1
Priscila Lúcia Pawloski, Camila Guimarães Moreira, Cintia Delai Silva Horinouchi, Daniel Fernandes, Luiz Renato Olchanheski, Willian Machado, Daniela Almeida Cabrini, Michele Dietrich, Kátia Paludo, Michel Fleith Otuki
Psoriasis is a complex inflammatory and hyperproliferative skin disease. The pathogenesis and mechanisms involved are not completely understood, which makes treatment a difficult issue. Angiotensin II, the most active peptide of the renin-angiotensin system, seems to be involved in processes related to psoriasis pathogenesis, such as inflammation and cell proliferation. The aim of this study was to investigate the influence of renin inhibition on inflammation parameters and keratinocyte proliferation in a mouse model of chronic skin inflammation induced by croton oil...
May 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29754833/discovery-of-benzimidazole-derivatives-as-orally-active-renin-inhibitors-optimization-of-3-5-disubstituted-piperidine-to-improve-pharmacokinetic-profile
#2
Hidekazu Tokuhara, Yasuhiro Imaeda, Yoshiyuki Fukase, Koichi Iwanaga, Naohiro Taya, Koji Watanabe, Ray Kanagawa, Keisuke Matsuda, Yumiko Kajimoto, Keiji Kusumoto, Mitsuyo Kondo, Gyorgy Snell, Craig A Behnke, Takanobu Kuroita
We previously identified 2-tert-butyl-4-[(3-methoxypropyl)amino]-N-(2-methylpropyl)-N-[(3S,5R)-5-(morpholin-4-ylcarbonyl)piperidin-3-yl]pyrimidine-5-carboxamide 3 as a potent renin inhibitor. Since 3 showed unacceptably low bioavailability (BA) in rats, structural modification, using SBDD and focused on physicochemical properties was conducted to improve its PK profile while maintaining renin inhibitory activity. Conversion of the amino group attached at the 4-position of pyrimidine to methylene group improved PK profile and decreased renin inhibitory activity...
April 27, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29715294/correction-treatment-combining-aliskiren-with-paricalcitol-is-effective-against-progressive-renal-tubulointerstitial-fibrosis-via-dual-blockade-of-intrarenal-renin
#3
Sungjin Chung, Soojeong Kim, Minyoung Kim, Eun Sil Koh, Seok Joon Shin, Cheol Whee Park, Yoon Sik Chang, Ho-Shik Kim
[This corrects the article DOI: 10.1371/journal.pone.0181757.].
2018: PloS One
https://www.readbyqxmd.com/read/29703387/food-drug-interactions-precipitated-by-fruit-juices-other-than-grapefruit-juice-an-update-review
#4
REVIEW
Meng Chen, Shu-Yi Zhou, Erlinda Fabriaga, Pian-Hong Zhang, Quan Zhou
This review addressed drug interactions precipitated by fruit juices other than grapefruit juice based on randomized controlled trials (RCTs). Literature was identified by searching PubMed, Cochrane Library, Scopus and Web of Science till December 30 2017. Among 46 finally included RCTs, six RCTs simply addressed pharmacodynamic interactions and 33 RCTs studied pharmacokinetic interactions, whereas seven RCTs investigated both pharmacokinetic and pharmacodynamic interactions. Twenty-two juice-drug combinations showed potential clinical relevance...
April 2018: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/29645283/sympathoexcitation-following-intermittent-hypoxia-in-rat-is-mediated-by-circulating-angiotensin-ii-acting-at-the-carotid-body-and-subfornical-organ
#5
Seung Jae Kim, Angelina Y Fong, Paul M Pilowsky, Stephen B G Abbott
Circulating angiotensin II (AngII) is vital for arterial pressure elevation following intermittent hypoxia in rats, but its importance in the induction of sympathetic changes is unclear. We tested the contribution of the RAS to the effects of acute intermittent hypoxia (AIH) in anaesthetized ventilated adult rats. AIH caused a 33.7 ± 2.9% increase in sympathetic nerve activity (SNA), and a one-fold increase in sympathetic peripheral chemoreflex sensitivity and central sympathetic-respiratory coupling. The sympathetic effects of AIH were prevented by blocking angiotensin type 1 receptors with systemic losartan and intermittent systemic injections of AngII (Int...
April 12, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29618841/greater-reductions-in-plasma-aldosterone-with-aliskiren-in-hypertensive-patients-with-higher-soluble-pro-renin-receptor-level
#6
Kanako Bokuda, Satoshi Morimoto, Yasufumi Seki, Midori Yatabe, Daisuke Watanabe, Junichi Yatabe, Takashi Ando, Satoru Shimizu, Hiroshi Itoh, Atsuhiro Ichihara
The (pro)renin receptor is important in the regulation of the tissue renin-angiotensin-aldosterone system. The benefits and safety of single-aliskiren treatment without other renin-angiotensin-aldosterone system inhibitors remain unclear. The serum level of the soluble form of the (pro)renin receptor is thought to be a biomarker reflecting the activity of the tissue renin-angiotensin-aldosterone system. We investigated the effects of single renin-angiotensin-aldosterone system blockade with aliskiren on renal and vascular functions and determined if serum level of the soluble (pro)renin receptor was a predictor of aliskiren efficacy in hypertensive patients with chronic kidney disease...
April 4, 2018: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/29560109/trpm8-and-raas-mediated-hypertension-is-critical-for-cold-induced-immunosuppression-in-mice
#7
Hao Chan, Hsuan-Shun Huang, Der-Shan Sun, Chung-Jen Lee, Te-Sheng Lien, Hsin-Hou Chang
Mechanisms underlying cold-induced immunosuppression remain unclear. Here we found that cold exposure leads to transient receptor potential melastatin 8 (TRPM8)-dependent, renin-angiotensin-aldosterone system (RAAS)-mediated hypertension, which subsequently induces small molecule and fluid extravasation, increases plasma Ig levels, and elicits immunosuppression. An effect is similar to the clinically-used immunosuppressive treatments of intravenous immunoglobulin (IVIg) against various inflammatory diseases, such as immune thrombocytopenia (ITP)...
February 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29470612/efficacy-of-aliskiren-supplementation-for-heart-failure-a-meta-analysis-of-randomized-controlled-trials
#8
REVIEW
Y Luo, Q Chen
BACKGROUND: Aliskiren might be beneficial for heart failure. However, the results of various studies are controversial. We conducted a systematic review and meta-analysis to explore the efficacy of aliskiren supplementation for heart failure. METHODS: PubMed, Embase, Web of Science, EBSCO, and the Cochrane Library databases were systematically searched. Randomized controlled trials (RCTs) assessing the efficacy of aliskiren for heart failure were included. Two investigators independently searched for articles, extracted data, and assessed the quality of included studies...
February 22, 2018: Herz
https://www.readbyqxmd.com/read/29465717/correction-aliskiren-therapy-in-hypertension-and-cardiovascular-disease-a-systematic-review-and-a-meta-analysis
#9
Shufang Fu, Xin Wen, Fei Han, Yin Long, Gaosi Xu
[This corrects the article DOI: 10.18632/oncotarget.19382.].
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29397816/-effects-of-four-renin-angiotensin-system-s-regulators-on-the-human-leukemia-hel-cell-growth
#10
Yi-Zhi Xu, Yun Wang, Dai-Ying He, Liang Zhang
OBJECTIVE: To investigate the effects of 4 renin-angiotensin system's(RAS) regulators (losartan, telmisartan, aliskiren and angiotenisin) on the human leukemia HEL cell growth. METHODS: The HEL cells were treated with losartan, telmisartan, aliskiren and Angiotensin-(1-7) (Ang-(1-7)) for 12 days, respectively. The cell proliferation was measured by CCK-8 kit, the cell cycle and apoptosis were measured by flow cytometry. RESULTS: The 10-7 mol/L Ang-(1-7) markedly inhibited the growth of HEL cells, blocked cells at G0 /G1 phase and markedly increased the late apoptotic cells (P< 0...
February 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29358184/curcumin-as-an-in-vivo-selective-intestinal-breast-cancer-resistance-protein-inhibitor-in-cynomolgus-monkeys
#11
Tsuyoshi Karibe, Tomoki Imaoka, Koji Abe, Osamu Ando
To estimate the clinical impact of pharmacokinetic modulation via breast cancer resistance protein (BCRP), in vivo approaches in nonclinical settings are desired in drug development. Clinical observation has identified curcumin as a promising candidate for in vivo selective BCRP inhibition, in addition to several well known inhibitors, such as lapatinib and pantoprazole. This study aimed to confirm the inhibitory efficacy of curcumin on gastrointestinal BCRP function in cynomolgus monkeys and to perform comparisons with lapatinib and pantoprazole...
May 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29331564/direct-renin-inhibition-is-not-enough-to-prevent-reactive-oxygen-species-generation-and-vascular-dysfunction-in-renovascular-hypertension
#12
Alisson Martins-Oliveira, Danielle A Guimaraes, Carla S Ceron, Elen Rizzi, Diogo M M Oliveira, Carlos R Tirapelli, Dulce E Casarini, Fernanda B Fernandes, Lucas C Pinheiro, Jose E Tanus-Santos
Renin-angiotensin system activation promotes oxidative stress and endothelial dysfunction. However, no previous study has examined the effects of the renin inhibitor aliskiren, either alone or combined with angiotensin II type 1 antagonists on alterations induced by two-kidney, one-clip (2K1C) hypertension. We compared the vascular effects of aliskiren (50mg/kg/day), losartan (10mg/kg/day), or both by gavage for 4 weeks in 2K1C and control rats. Treatment with losartan, aliskiren, or both exerted similar antihypertensive effects...
February 15, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29295576/intracellular-renin-inhibits-mitochondrial-permeability-transition-pore-via-activated-mitochondrial-extracellular-signal-regulated-kinase-erk-1-2-during-ischemia-in-diabetic-hearts
#13
Terumori Satoh, Masao Saotome, Hideki Katoh, Daishi Nonaka, Prottoy Hasan, Hideharu Hayashi, Yuichiro Maekawa
Although beneficial effects of non-secreting intracellular renin (ns-renin) against ischemia have been reported, the precise mechanism remains unclear. In this study, we investigated the roles of ns-renin and mitochondrial extracellular signal-related kinase (ERK) 1/2 on mitochondrial permeability transition pore (mPTP) opening during ischemia in diabetes mellitus (DM) hearts. When isolated hearts from Wistar rats (non-DM hearts) and Goto-Kakizaki rats (DM hearts) were subjected to ischemia for 70 min by left anterior descending coronary artery ligation, DM hearts exhibited higher left ventricular (LV) developed pressure and lower LV end-diastolic pressure than non-DM hearts, suggesting ischemic resistance...
December 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29230587/arterial-wall-hypertrophy-is-ameliorated-by-%C3%AE-2-adrenergic-receptor-antagonist-or-aliskiren-in-kidneys-of-angiotensinogen-knockout-mice
#14
Haruka Nakamori, Shin-Ichiro Yoshida, Hiroaki Ishiguro, Shota Suzuki, Hiroaki Yasuzaki, Tatsuo Hashimoto, Tomoaki Ishigami, Nobuhito Hirawa, Yoshiyuki Toya, Satoshi Umemura, Kouichi Tamura
BACKGROUND: Arterial hypertrophy and interstitial fibrosis are important characteristics in kidneys of angiotensinogen-knockout (Atg-/- ) mice. In these mice, which exhibit polyuria and hypotension, sympathetic nerve signaling is estimated to be compensatorily hyperactive. Furthermore, transforming growth factor (TGF)-β1 is overexpressed in mice kidneys. To determine whether sympathetic nerve signaling and TGF-β1 exacerbate arterial hypertrophy and interstitial fibrosis, intervention studies of such signaling are required...
December 11, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/29198406/comparison-of-the-effect-of-aliskiren-versus-negative-controls-on-aortic-stiffness-in-patients-with-marfan-syndrome-under-treatment-with-atenolol
#15
Ji-Won Hwang, Eun Kyoung Kim, Shin Yi Jang, Tae-Young Chung, Chang-Seok Ki, Kiick Sung, Sung Mok Kim, Joonghyun Ahn, Keumhee Carriere, Yeon Hyeon Choe, Sung-A Chang, Duk-Kyung Kim
INTRODUCTION AND OBJECTIVES: The aim of this study was to evaluate the effect of aliskiren on aortic stiffness in patients with Marfan syndrome (MS). METHODS: Twenty-eight MS patients (mean age ± standard deviation: 32.6 ± 10.6 years) were recruited from November 2009 to October 2014. All patients were receiving atenolol as standard beta-blocker therapy. A prospective randomization process was performed to assign participants to either aliskiren treatment (150-300mg orally per day) or no aliskiren treatment (negative control) in an open-label design...
November 29, 2017: Revista Española de Cardiología
https://www.readbyqxmd.com/read/29191768/interactions-of-aliskiren-a-direct-renin-inhibitor-with-antiepileptic-drugs-in-the-test-of-maximal-electroshock-in-mice
#16
Krzysztof Łukawski, Grzegorz Raszewski, Stanisław J Czuczwar
Experimental studies showed that certain angiotensin-converting enzyme inhibitors and angiotensin AT1 receptor antagonists can decrease seizure severity in rodents. Additionally, some of these blockers of the renin-angiotensin system have been documented to enhance the anticonvulsant activity of antiepileptic drugs against maximal electroshock-induced seizures. The aim of the current study was to investigate the effect of aliskiren, a direct renin inhibitor and a novel antihypertensive drug, on the protective action of numerous antiepileptic drugs (carbamazepine, valproate, clonazepam, phenobarbital, oxcarbazepine, lamotrigine, topiramate and pregabalin) in the test of maximal electroshock in mice...
January 15, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29184499/aliskiren-improves-ischemia-and-oxygen-glucose-deprivation-induced-cardiac-injury-through-activation-of-autophagy-and-amp-activated-protein-kinase
#17
Ming-Hsien Chiang, Chan-Jung Liang, Chen-Wei Liu, Bo-Jhih Pan, Wen-Ping Chen, Yi-Fan Yang, I-Ta Lee, Jaw-Shiun Tsai, Chiang-Wen Lee, Yuh-Lien Chen
Aliskiren is a direct renin inhibitor that has been effective in anti-hypertension. We investigated whether aliskiren could improve the ischemia-induced cardiac injury and whether the autophagy was involved in this effect. A myocardial infarction (MI) model was created by the ligation of the left anterior coronary artery in C57J/BL6 mice. They were treated for 1, 3, 7, and 14 days with vehicle or aliskiren (25 mg/kg/day via subcutaneous injection). In vivo , the MI mice exhibited worse cardiac function by echocardiographic assessment and showed larger myocardial scarring by light microscopy, whereas aliskiren treatment reversed these effects, which were also associated with the changes in caspase-3 and Bcl-2 expression as well as in the number of apoptotic cells...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29179525/aliskiren-therapy-in-hypertension-and-cardiovascular-disease-a-systematic-review-and-a-meta-analysis
#18
REVIEW
Shufang Fu, Xin Wen, Fei Han, Yin Long, Gaosi Xu
The efficacy and safety of aliskiren combination therapy with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in patients with hypertension and cardiovascular disease remains attractive attention. We searched the Cochrane Central Register, the Clinical Trials Registry, EMBASE, MEDLINE and PubMed for relevant literatures up to January 2017. A total of 13 randomized controlled trials (RCTs) with 12222 patients were included in this study, and the combined results indicated that aliskiren in combination therapy with ACEIs or ARBs had remarkable effects in reducing systolic blood pressure (SBP) [weighted mean differences (WMD), -4...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29172824/aliskiren-and-valsartan-in-combination-is-a-promising-therapy-for-hypertensive-renal-injury-in-rats
#19
Hala Salah Abdel Kawy
Neither ACEI nor ARBs completely repress the RAAS. Aliskiren is a newer agent that inhibits renin. However, it increases the biosynthesis and secretion of renin and prorenin, that might induce renal tissue damage. This study was conducted to investigate the renoprotective effects of aliskiren and valsartan the ARB, either alone or in combination, on hypertensive nephropathy induced by L-NAME. Aliskiren (50 mg/kg/daily i.p.), valsartan (10 mg/kg daily i.p.) alone or in half dose combination were administered with L-NAME (30-40 mg daily in drinking water) for 8 weeks...
November 27, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29152151/aliskiren-for-heart-failure-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#20
Hongzhi Liu, Hongxing Luo, Suqin Wang, Cong Zhang, Jialiang Hao, Chuanyu Gao
Objective: To systematically review and synthesize the currently available evidence of aliskiren for the treatment of heart failure. Materials and Methods: We systematically searched the Cochrane, Embase and PubMed databases to identify the randomized controlled trials (RCT) on the effects of aliskiren on heart failure. Data were synthesized with random effects model and presented in forest plot. Publication bias was evaluated with funnel plot. Heterogeneity was evaluated with Begg's test and Egger's test...
October 20, 2017: Oncotarget
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