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Masahiko Gosho
Hypoglycemia is the most important complication of antidiabetic medications. Most patients with diabetes mellitus take multiple medications. In this study, we explored clinical drug-drug interactions that result in hypoglycemia by analyzing the Japanese Adverse Drug Event Report (JADER) database. The primary outcome was the report of hypoglycemia. The Norén and Gosho methods, which quantitatively measure the discrepancy between the observed and expected number of adverse events under the combination of 2 drugs, were used as the criteria for detecting drug-drug interactions...
May 15, 2018: Journal of Clinical Pharmacology
Jinliang Liu, Shinji Yasuno, Koji Oba, Manako Konda, Chikako Ichihara, Hiromi Kitao, Yoshihiro Kuwabara, Kenji Ueshima
OBJECTIVE: During the Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial, patients with hypertension who received amlodipine had similar cardiovascular risks as those who received candesartan. We conducted a post-trial study, the Candesartan Antihypertensive Survival Evaluation in Japan 10-year follow-up (CASE-J 10). This study aimed to confirm the long-term cardiovascular effects of candesartan and amlodipine. METHODS: Case report forms were sent to CASE-J investigators who agreed to participate in the CASE-J 10...
May 9, 2018: Journal of Hypertension
Abdel Naser Zaid, Asma Radwan, Nidal Jaradat, Ayman Mousa, Nadia Ghazal, Rana Bustami
In this study, the in vitro and in vivo interchangeability between generic candesartan 16 mg and the branded formulation was assessed. The in vitro release of these products was conducted in 3 pH media (1.2, 5.0, and 6.8), and similarity factors (f2 ) were calculated. This bioequivalence study was a randomized, 2-period crossover study that included 42 healthy adult male subjects under fasting conditions with a 9-day washout. The pharmacokinetic (PK) parameters AUC0-last , AUC0-∞ , and Cmax , tmax , and the elimination half-life time were assessed based on the plasma concentrations of candesartan, using a newly developed and validated liquid chromatography-tandem mass spectrometry bioanalytical method with acceptable degrees of linearity, sensitivity, precision, and accuracy...
May 10, 2018: Clinical Pharmacology in Drug Development
Simon de Denus, Marie-Pierre Dubé, René Fouodjio, Thao Huynh, Marie-Hélène LeBlanc, Serge Lepage, Richard Sheppard, Nadia Giannetti, Joël Lavoie, Asmaa Mansour, Sylvie Provost, Valérie Normand, Ian Mongrain, Mathieu Langlois, Eileen O'Meara, Anique Ducharme, Normand Racine, Marie-Claude Guertin, Jacques Turgeon, Michael S Phillips, Jean-Lucien Rouleau, Jean-Claude Tardif, Michel White
AIM: To evaluate the impact of AGTR1 A1166C (rs5186) on the response to candesartan in patients with heart failure. MATERIALS & METHODS: Prospective, multicentre, open-label study. We studied 299 symptomatic patients with heart failure presenting a left ventricular ejection fraction ≤40%. RESULTS: Reductions in the primary end points of natriuretic peptides were not significantly associated with AGTR1 A1166C. Nevertheless, carrying the 1166C allele was associated with a greater compensatory increase in renin activity (p = 0...
April 27, 2018: Pharmacogenomics
A Maruschak, E Shorikov, I Timofiichuk, I Davydenko, K Slobodyan
Choosing a method of treating arterial hypertension remains an urgent problem today. For effective therapy, it is necessary to select hypotensive drugs that not only effectively reduce the pressure, but also contribute to the restoration of the structure of tissues sensitive to oscillations of arterial pressure. The purpose of this study was to conduct a comparative analysis of the effect of angiotensin 2-candesartan receptor antagonist and angiotensin converting factor ramipril on pathomorphological changes in the myocardium, kidney, and liver in SHR lines that received treatment for 7 days (short) and 21 days (prolonged therapy ) The study was conducted on 20 spontaneously hypertensive rats with a mass of 248...
March 2018: Georgian Medical News
Mohammad Rasheduzzaman, Sang-Youel Park
Angiotensin II type 1 receptor blockers (ARBs) are widely used as antihypertensive drugs. Candesartan is an ARB that has also been known for its anticancer effects but the exact molecular mechanism is remaining elusive. In this research, we showed for the first time that candesartan treatment significantly sensitized human lung adenocarcinoma cells to Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis by targeting TRAIL-DR5. TRAIL selectively kills cancer cells by binding to death receptors on the cell membrane, beyond the levels causing minimal toxicity in normal cells...
April 22, 2018: Experimental Cell Research
Kristy L Jackson, Francine Z Marques, Kyungjoon Lim, Pamela J Davern, Geoffrey A Head
Objective: Genetically hypertensive BPH/2J mice are recognized as a neurogenic model of hypertension, primarily based on sympathetic overactivity and greater neuronal activity in cardiovascular regulatory brain regions. Greater activity of the central renin angiotensin system (RAS) and reactive oxygen species (ROS) reportedly contribute to other models of hypertension. Importantly the peripheral RAS contributes to the hypertension in BPH/2J mice, predominantly during the dark period of the 24 h light cycle...
2018: Frontiers in Physiology
Tomoko Kakio, Hitomi Nagase, Takashi Takaoka, Naoko Yoshida, Junichi Hirakawa, Susan Macha, Takashi Hiroshima, Yukihiro Ikeda, Hirohito Tsuboi, Kazuko Kimura
The World Health Organization has warned that substandard and falsified medical products (SFs) can harm patients and fail to treat the diseases for which they were intended, and they affect every region of the world, leading to loss of confidence in medicines, health-care providers, and health systems. Therefore, development of analytical procedures to detect SFs is extremely important. In this study, we investigated the quality of pharmaceutical tablets containing the antihypertensive candesartan cilexetil, collected in China, Indonesia, Japan, and Myanmar, using the Japanese pharmacopeial analytical procedures for quality control, together with principal component analysis (PCA) of Raman spectrum obtained with handheld Raman spectrometer...
April 2, 2018: American Journal of Tropical Medicine and Hygiene
Di Zhao, Hui Liu, Pingshuan Dong
OBJECTIVE: The comparison of antihypertensive effects between telmisartan and candesartan in patients with essential hypertension has been investigated in several small studies. The results were not consistent. We performed this meta-analysis determining the antihypertensive effect of telmisartan versus candesartan in these patients. METHODS: We searched Pubmed, Web of Science, and Cochrane Central for all published studies comparing the antihypertensive effects between telmisartan and candesartan in patients with essential hypertension...
March 28, 2018: Clinical and Experimental Hypertension: CHE
Hua Jin, Yiping Wang, Dong Wang, Lei Zhang
Background . The activation of NF-kappa B (NF/kB) signaling pathway plays an important role in the process of epithelial-mesenchymal transition (EMT) and renal interstitial fibrosis (RIF) in renal tubules. The process of oxidative stress reaction in kidney is via excessive reactive oxygen species (ROS) production to activate NF/kB signaling pathway. Qingshen Granule (QSG) is an effective Chinese formula utilized to treat chronic renal failure. Previous studies confirmed that QSG could inhibit RIF in unilateral ureteral obstruction (UUO) rats...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Takanobu Takezako, Hamiyet Unal, Sadashiva S Karnik, Koichi Node
BACKGROUND AND PURPOSE: Diseases such as hypertension and renal-allograft rejection are accompanied by chronic agonist-independent signaling by the angiotensin II (Ang II) type 1 receptor (AT1R). The current treatment paradigm for these diseases embraces the preferred use of inverse agonist AT1R blockers (ARBs). However, variability in the inverse agonist activities of common biphenyl-tetrazole ARBs for the active state of AT1R often leads to treatment failure. Therefore, characterization of robust inverse agonist ARBs for the active state of AT1R is necessary...
March 23, 2018: British Journal of Pharmacology
Pablo Garrido-Gil, Antonio Dominguez-Meijide, Rosario Moratalla, Maria J Guerra, Jose L Labandeira-Garcia
Gastrointestinal dysfunction is a common problem in the elderly. Aging-related changes in interactions between local dopaminergic and renin-angiotensin systems (RAS) have been observed in the brain, renal and vascular tissues. However, it is not known if these interactions also occur in the gut, and are dysregulated with aging. We showed a mutual regulation between the colonic dopaminergic system and RAS using young and aged mice deficient for major angiotensin and dopamine receptors. Aged rats showed a marked decrease in colonic dopamine D2 receptor expression, together with an increase in angiotensin type 1 (AT1) receptor expression, a decrease in angiotensin type 2 (AT2) receptor expression (i...
February 16, 2018: Oncotarget
Peter Bramlage, Stefanie Schmidt, Helen Sims
Fixed-dose combinations (FDC) have been developed to reduce the pill burden for hypertensive patients. Data on fixed-dose or free-dose (freeDC) ramipril/amlodipine (R/A) or candesartan/amlodipine (C/A) combination treatment initiation were assessed. 71 463 patients were prescribed R/A and 10 495 C/A. For both R/A and C/A, FDC patients were younger (both P < .001) and less comorbid. Prior MI (OR: 0.61 and 0.60), prior stroke (OR: 0.68 and 0.70) and CHD (OR: 0.68 and 0.64) were negatively associated with FDC use, whereas hyperlipidemia was positively associated (OR: 1...
April 2018: Journal of Clinical Hypertension
Antônio da Silva Novaes, Rosemara Silva Ribeiro, Luciana Guilhermino Pereira, Fernanda Teixeira Borges, Mirian Aparecida Boim
Biological effects of angiotensin II (AngII) such as regulation of AngII target genes may be triggered by interaction of AngII with intracellular AngII receptor types 1 and 2 (AT1 and AT2 ), defined as intracrine response. The aim of this study was to examine the presence of AT1 and AT2 receptors in nuclear membrane of human mesangial cells (HMCs) and evaluate the possible biological effects mediated by intracellular AT1 through an intracrine mechanism. Subcellular distribution of AT1 and AT2 was evaluated by immunofluorescence and by western blot in isolated nuclear extract...
February 17, 2018: Molecular and Cellular Biochemistry
Xiaojin Gong, Qian Zhao, Mu Song, Feng Xue
In our study, we report on the design and characterization of a combined angiogenesis therapy for breast cancer based on well-formed amine-functionalized silica nanoparticles (SLNs). The aminefunctionalized SLNs was employed to simultaneously deliver angiostatin (ANG) plasmid and candesartan (CD) to the same cancer cell. The well-formed ANG/CD/SLNs exhibited small particle size, reasonable positive charges, excellent loading of drug and gene in vitro. Moreover, aminefunctionalized SLNs were almost no cytotoxicity...
April 1, 2018: Journal of Nanoscience and Nanotechnology
Olga Gawryś, Iwona Baranowska, Katarzyna Gawarecka, Ewa Świeżewska, Jolanta Dyniewicz, Krzysztof H Olszyński, Marek Masnyk, Marek Chmielewski, Elżbieta Kompanowska-Jezierska
Novel lipid-based carriers, composed of cationic derivatives of polyisoprenoid alcohols (amino-prenols, APrens) and 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE), were designed. The carriers, which were previously shown to be nontoxic to living organisms, were now tested if suitable for administration of candesartan, an antihypertensive drug. Spontaneously hypertensive rats (SHR) received injections of candesartan (0.1 mg/kg body weight per day; s.c.) in freshly prepared carriers for two weeks...
April 2018: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Lars H Lund, Brian Claggett, Jiankang Liu, Carolyn S Lam, Pardeep S Jhund, Giuseppe M Rosano, Karl Swedberg, Salim Yusuf, Christopher B Granger, Marc A Pfeffer, John J V McMurray, Scott D Solomon
AIMS: We tested the hypothesis that candesartan improves outcomes in heart failure (HF) with mid-range ejection fraction [HFmrEF; ejection fraction (EF) 40-49%]. METHODS AND RESULTS: In 7598 patients enrolled in the CHARM Programme (HF across the spectrum of EF), we assessed characteristics, outcomes and treatment effect of candesartan according to EF. Patients with HFmrEF (n = 1322, 17%) were similar to those with HF with reduced EF (HFrEF; n = 4323, 57%) with respect to some characteristics, and intermediate between HFrEF and HF with preserved EF (HFpEF; n = 1953, 26%) with respect to others...
February 12, 2018: European Journal of Heart Failure
Rui-Juan Zhuang, Wei-Dong Jin, Xiao-Yan Wang, Xue-Ming Wu
Olmesartan (OL) is the pharmacologically active metabolite of Olmesartan medoxomil (OM), an FDA-approved angiotensin II receptor antagonist for administrating cardiovascular diseases. The drug has been found to have potential effects on diverse protein kinase signaling involved in the pathogenesis of atherosclerosis, either by directly inhibiting the hub kinases or by indirectly modulating marginal members in the signaling pathways. In the present study, we computationally model the kinase-chemical Interaction Profile between six OL-related chemicals (i...
March 2018: Journal of Molecular Graphics & Modelling
Amel Chaabane, Najeh Ben Fadhel, Zohra Chadli, Haifa Ben Romdhane, Nadia Ben Fredj, Naceur A Boughattas, Karim Aouam
PURPOSE: To assess delayed-type cutaneous reactions (DTCRs) related to drugs, using a case-control approach to qualify drug risks. METHODS: The study used the Tunisian pharmacovigilance database of Monastir. The association between drugs and DTCRs was assessed using a case/non-case method. Drugs were grouped according to the ATC Classification System. Patients were defined as "cases" if they have developed DTCRs regardless of the causality assessment. All other reports were "non-cases"...
February 3, 2018: European Journal of Internal Medicine
Hui Li, Jun-Ling Zhao, Yuan-Ming Zhang, Su-Xia Han
BACKGROUND AND AIM: Increasing evidence confirms that potassium channels are essential for lymphocyte activation, suggesting an involvement in the development of hypertension. Moreover, chronic inflammation is regarded as a direct or indirect manifestation of hypertension, highlighting the theoretical mechanisms. In this study, we investigated changes in KCa3.1 potassium channel expression in the blood of hypertensive and healthy Kazakh people in north-west China. METHODS: Flow cytometry technology was used for T-lymphocyte subtype analysis...
2018: Clinical and Experimental Hypertension: CHE
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