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Qing Gao, Zhou Ou, Teng Jiang, You-Yong Tian, Jun-Shan Zhou, Liang Wu, Jian-Quan Shi, Ying-Dong Zhang
Loss of dopaminergic neurons within the substantia nigra (SN) is a pathological hallmark of Parkinson's disease (PD), which leads to the onset of motor symptoms. Previously, our in vitro studies revealed that Angiotensin II (Ang II) induced apoptosis of dopaminergic neurons through its type 1 receptor (AT1R), but these findings needed to be confirmed via animal experiments. Here, using a rotenone-induced rat model of PD, we observed an overactivation of Ang II/AT1R axis in the SN, since Ang II level and AT1R expression were markedly increased...
April 11, 2017: Oncotarget
Marie Harthøj Hjermitslev, Daniela Grimm, Markus Wehland, Ulf Simonsen, Marcus Krüger
Azilsartan medoxomil was approved by the United States Food and Drug Administration in 2011 for the treatment of hypertension and has shown promising results both in blood pressure (BP) reduction and in tolerability, but has not yet been taken into practice to the same extent as other angiotensin-II receptor blockers (ARBs) that have been on the market for a longer period. This article is protected by copyright. All rights reserved.
April 26, 2017: Basic & Clinical Pharmacology & Toxicology
Yun-Wei Li, Yan-Ming Li, Yan Hon, Qi-Lin Wan, Rui-Li He, Zhi-Zhong Wang, Cui-Hua Zhao
BACKGROUND AND OBJECTIVES: Ischemic post-conditioning (PostC) has been demonstrated as a novel strategy to harness nature's protection against myocardial ischemia-reperfusion (I/R). Hypercholesterolemia (HC) has been reported to block the effect of PostC on the heart. Angiotensin II type-1 (AT1) modulators have shown benefits in myocardial ischemia. The present study investigates the effect of a novel inhibitor of AT1, azilsartan in PostC of the heart of normocholesterolemic (NC) and HC rats...
March 2017: Korean Circulation Journal
V V Skibitskiy, A V Fendrikova, D V Sirotenko, A V Skibitskiy
OBJECTIVE: Determination of the effectiveness and safety of different dosing regimens during the day (in the morning or at bedtime) combination therapy including azilsartan medoxomil in patients with essential hypertension and metabolic syndrome (MS). DESIGN AND METHODS: The study included 60 patients with uncontrolled hypertension and MS (age median - 59 (54-65) years). Patients were randomized in two groups: group 1 (n=30) received azilsartan medoxomil 40 mg/day, and indapamide retard 1,5 mg/day in the morning; group 2 (n=30)- azilsartan medoxomoil 40 mg at bedtime and indapamide retard 1,5 mg in the morning...
October 2016: Kardiologiia
Y A Vasyuk, E Y Shupenina, V V Nesvetov, E A Nesterova, E I Golubkova
Arterial hypertension (AH) is one of the most common cardiovascular disease. Angiotensin II (AT II), the hormone of renin-angiotensin-aldosterone system, realizes its negative effects through AT 1 receptors - application point of angiotensin receptor blockers (ARB). Due to different dissociation AT 1 receptors properties some ARBs are more effective than others. Multiply multicenter randomized and observational studies approve the effectiveness and safety of azilsartan medoxomil in patients with AH 1-2 grade...
December 2016: Kardiologiia
Yuki Kakio, Haruhito A Uchida, Ryoko Umebayashi, Hidemi Takeuchi, Yuka Okuyama, Yoshihisa Hanayama, Jun Wada
BACKGROUND: Olmesartan and azilsartan, angiotensin II receptor blockers (ARBs), are expected to decrease blood pressure more than the other ARBs. We conducted randomized-controlled trials to compare the practical efficacy of olmesartan with azilsartan. METHODS: Eighty-four patients treated with the conventional ARBs for more than 3 months were assigned randomly to receive either 20 mg of olmesartan (olmesartan medoxomil, OL group) or 20 mg of azilsartan (azilsartan, not azilsartan medoxomil, AZ group) once daily for 16 weeks...
April 2017: Blood Pressure Monitoring
Jin Guan, Jie Min, Feng Yan, Wen-Ya Xu, Shuang Shi, Si-Lin Wang
A new gas chromatographic method for the simultaneous determination of six organic residual solvents (acetonitrile, tetrahydrofuran, ethanol, acetone, 2-propanol and ethyl acetate) in azilsartan bulk drug is described. The chromatographic determination was achieved on an OV-624 capillary column employing programmed temperature within 21 min. The validation was carried out according to International Conference on Harmonization validation guidelines. The method was shown to be specific (no interference in the blank solution), sensitive (Limit of detection can achieve 1...
April 1, 2017: Journal of Chromatographic Science
Kota Motozato, Shin-Ichiro Miura, Yuhei Shiga, Takaaki Kusumoto, Keijiro Saku
BACKGROUND: Guidelines for the management of hypertension recommend the use of drugs with different mechanisms of action in antihypertensive regimens that include single-pill fixed-dose combinations of medications. There is some controversy regarding which single-pill fixed-dose combinations of angiotensin II type 1 receptor blockers (ARBs) and calcium channel blockers (CCBs) are effective at reducing blood pressure (BP). METHODS: Forty hypertensive patients who were receiving a single-pill fixed-dose combination of valsartan 80 mg/day and amlodipine 5 mg/day or irbesartan 100 mg/day and amlodipine 5 mg/day were enrolled...
December 2016: Journal of Clinical Medicine Research
Joji Inamasu, Shunsuke Nakae, Kazuhide Adachi, Yuichi Hirose
BACKGROUND AND OBJECTIVE: In patients with hypertensive intracerebral hemorrhage (HICH), intravenous nicardipine is primarily used to lower blood pressure (BP). However, there are few studies investigating the role of oral antihypertensives administered after intravenous nicardipine to prevent BP from rising. Angiotensin II receptor blockers (ARBs) may be beneficial in HICH patients not only as antihypertensives but also by lowering plasma catecholamine levels. A prospective randomized study was conducted between January 2015 and March 2016 to comparatively evaluate the efficacy of two ARBs (azilsartan vs...
February 2017: Blood Pressure Monitoring
Ramesh R Dargad, Jai D Parekh, Rohit R Dargad, Shweta Kukrety
OBJECTIVE: To describe the efficacy and safety profile of the new angiotensin receptor blocker (ARB), "Azilsartan Medoxomil", reviewing data available from both clinical and pre-clinical studies. MATERIAL: We completed a review of the English literature from PubMed using the keywords- azilsartan medoxomil, angiotensin receptor blockers (ARB), angiotensin converting enzyme inhibitors (ACEi) and hypertension. DATA EVALUATION: Many clinical trials have been conducted comparing the efficacy of azilsartan with other ARB's and also with the ACEi ramipril...
March 2016: Journal of the Association of Physicians of India
Sen Adachi, Shin-Ichiro Miura, Yuhei Shiga, Tadaaki Arimura, Takashi Kuwano, Ken Kitajima, Amane Ike, Makoto Sugihara, Atsushi Iwata, Hiroaki Nishikawa, Natsumi Morito, Keijiro Saku
BACKGROUND: We compared the efficacy and safety of azilsartan to those of olmesartan in a prospective, randomized clinical trial. METHODS: Forty-four hypertensive patients who had coronary artery disease (CAD) were enrolled. We randomly assigned patients to changeover from their prior angiotensin II receptor blockers (ARBs) to either azilsartan or olmesartan, and followed the patients for 12 weeks. RESULTS: Office systolic blood pressure (SBP) in the azilsartan group was significantly decreased after 12 weeks...
October 2016: Journal of Clinical Medicine Research
Alfonso Perez, Charlie Cao
In this phase 2, multicenter, parallel-group, double-blind, dose-ranging study, hypertensive adults (n=449) were randomized to receive one of five doses of a capsule formulation of azilsartan medoxomil (AZL-M; 5, 10, 20, 40, 80 mg), olmesartan medoxomil (OLM) 20 mg, or placebo once daily. The primary endpoint was change in trough clinic diastolic blood pressure (DBP) at week 8. AZL-M provided rapid statistically and clinically significant reductions in DBP and systolic blood pressure (SBP) vs placebo at all doses except 5 mg...
March 2017: Journal of Clinical Hypertension
Georgios Georgiopoulos, Vasiliki Katsi, Dimitrios Oikonomou, Georgia Vamvakou, Evangelia Koutli, Aggeliki Laina, Constantinos Tsioufis, Petros Nihoyannopoulos, Dimitrios Tousoulis
BACKGROUND: Hypertension related cardiovascular (CV) complications could be amplified by the presence of metabolic co-morbidities. Azilsartan medoxomil (AZL-M) is the eighth approved member of angiotensin II receptor blockers (ARBs), a drug class of high priority in the management of hypertensive subjects with diabetes mellitus type II (DMII). METHODS: Under this prism, we performed a systematic review of the literature for all relevant articles in order to evaluate the efficacy, safety, and possible clinical role of AZL-M in hypertensive diabetic patients...
2016: Frontiers in Pharmacology
Yuichi Hayashi, Shohei Nishida, Akira Takekoshi, Muneharu Murakami, Megumi Yamada, Akio Kimura, Akio Suzuki, Takashi Inuzuka
Lithium carbonate is considered to be a first-line treatment for bipolar disorder; however, this drug has a narrow therapeutic window, and lithium intoxication is commonly induced by various drugs interaction and situations. We herein report a case of lithium intoxication induced by the administration of an antihypertensive agent targeting the angiotensin 1 (AT1) subtype of the angiotensin II receptor in a 65-year-old woman with a 40-year history of bipolar disorder type 1, and 1-year history of essential hypertension...
2016: Nihon Ronen Igakkai Zasshi. Japanese Journal of Geriatrics
Caroline Dudkowski, Aziz Karim, Melvin Munsaka
Azilsartan medoxomil is a long-acting angiotensin II receptor blocker used to treat hypertension as monotherapy or in fixed-dose combination (FDC) with chlorthalidone. This study assessed the effects of food intake on the plasma pharmacokinetics of the active moiety, azilsartan, and of chlorthalidone when administered as separate tablets or in FDC. Cohort 1 (n = 24) received azilsartan medoxomil (80 mg) and chlorthalidone (25 mg) once in a fasted condition and once 30 minutes after the initiation of a high-fat meal (fed)...
September 2016: Clinical Pharmacology in Drug Development
Tomohito Kamada, Mutsuharu Hayashi, Wakaya Fujiwara, Daiji Yoshikawa, Daisuke Mukaide, Yoshinori Sugishita, Masataka Yoshinaga, Takehiro Itoh, Hiroatsu Yokoi, Junichi Ishii, Eiichi Watanabe, Yukio Ozaki, Hideo Izawa
OBJECTIVES: The number of elderly patients with hypertension has been steadily increasing. However, there are limited data on the safety and efficacy of the new angiotensin type 1 receptor blocker (ARB) azilsartan in elderly patients with hypertension. We investigated the clinical efficacy and safety of azilsartan in this population. METHODS: The study population comprised 56 ambulatory patients with essential hypertension. We evaluated the reduction in blood pressure and safety after 12 weeks of treatment with azilsartan in 29 hypertensive patients ≥65 years of age (aged group) in comparison with the findings in 27 patients <65 years of age (non-aged group)...
January 2017: Drug and Chemical Toxicology
Alfonso Perez, Charlie Cao
This was a phase 2, multicenter, randomized, parallel-group, double-blind dose-ranging study. Hypertensive adults (n=555) received one of five doses of azilsartan (AZL; 2.5, 5, 10, 20, 40 mg), olmesartan medoxomil (OLM) 20 mg, or placebo once daily. The primary endpoint was change in trough clinic diastolic blood pressure (DBP) at week 8. Compared with placebo, all AZL doses (except 2.5 mg) provided statistically and clinically significant reductions in DBP and systolic blood pressure (SBP) based on both clinic blood pressure (BP) and 24-hour ambulatory BP monitoring (ABPM)...
July 15, 2016: Journal of Clinical Hypertension
Manami Kaneko, Tomoko Satomi, Shuji Fujiwara, Hidefumi Uchiyama, Keiji Kusumoto, Tomoyuki Nishimoto
Our study measured circulating microRNA (miRNA) levels in the plasma of calsequestrin (CSQ)-tg mouse, a severe heart failure model, and evaluated whether treatment with angiotensin II type 1 receptor blocker, azilsartan medoxomil (AZL-M) influenced their levels using miRNA array analysis. MiR-146a, miR-149, miR-150, and miR-342-3p were reproducibly reduced in the plasma of CSQ-tg mice. Among them, miR-146a and miR-342-3p were significantly restored by AZL-M, which were associated with improvement of survival rate and reduction of congestion...
May 2017: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
Luke J Laffin, Colleen Majewski, Chuanhong Liao, George L Bakris
Increased abdominal obesity is associated with increased cardiovascular risk, especially in African American women. The adipocyte is documented to produce a number of inflammatory factors including the hormone aldosterone. There are very few data documenting aldosterone production from adipocytes of postmenopausal women as well as data demonstrating the effects of angiotensin receptor blockade (ARB) on its production in predominately African American women. The authors hypothesize that increased central adipocyte mass in obese postmenopausal women contributes to increased production of aldosterone that is suppressed with the ARB azilsartan medoxomil...
December 2016: Journal of Clinical Hypertension
Ruirui Yang, Zhiqiang Luo, Yang Liu, Mohan Sun, Ling Zheng, Yingying Chen, Yanping Li, Hao Wang, Lingzhu Chen, Ming Wu, Huihui Zhao
BACKGROUND: Angiotensin receptor blockers (ARBs) are the most recent class of agents for the treatment of hypertension. However, ARBs may cause a low incidence of headache, upper respiratory infection, back pain, muscle cramps, fatigue, dizziness, and many other side effects. In some cases, such toxicity is associated with pharmacokinetic alterations. METHODS: The cytochrome P450 (CYP) enzyme system plays an important role in a lot of clinically important pharmacokinetic drug interactions...
2016: Current Drug Metabolism
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