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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...
February 19, 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. The rats' arterial pressure was measured by telemetry...
February 13, 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...
January 30, 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...
February 1, 2018: Clinical and Experimental Hypertension: CHE
Joanna A Phipps, Kirstan A Vessey, Alice Brandli, Nupur Nag, Mai X Tran, Andrew I Jobling, Erica L Fletcher
Purpose: This study explored whether the proangiogenic factor Angiotensin II (AngII) had a direct effect on the activation state of microglia via the Angiotensin type 1 receptor (AT1-R). Methods: Microglial dynamic activity was investigated in live retinal flatmounts from adult Cx3Cr1+/GFP mice under control, AngII (5 μM) or AngII (5 μM) + candesartan (0.227 μM) conditions. The effects of intravitreal administration of AngII (10 mM) were also investigated at 24 hours, with retinae processed for immunocytochemistry, flow cytometry, or inflammatory quantitative PCR arrays...
January 1, 2018: Investigative Ophthalmology & Visual Science
Nofar Torika, Keren Asraf, Ron N Apte, Sigal Fleisher-Berkovich
AIMS: Alzheimer's disease (AD) pathology is associated with brain inflammation involving microglia and astrocytes. The renin-angiotensin system contributes to brain inflammation associated with AD pathology. This study aimed to investigate the role of candesartan, an angiotensin II type 1 receptor blocker, in modulation of glial functions associated with AD. METHODS: Focusing on the role of candesartan in glial inflammation, we evaluated inflammatory mediators' levels, secreted by lipopolysaccharide-induced microglia following candesartan treatment...
January 24, 2018: CNS Neuroscience & Therapeutics
Juliana Munari Oliveira Pinto, Aline Franciane Leão, Manoela Klüppel Riekes, Maria Terezinha França, Hellen Karine Stulzer
Among the strategies to improve the biopharmaceutic properties of poorly soluble drugs, Supersaturating Drug Delivery Systems like polymer-based amorphous solid dispersions (SD) have been successfully applied. The screening of appropriate polymeric carriers to compose SD is a crucial point on their development. In this study, hydroxypropylmethylcellulose (HPMC), hydroxypropylmethylcellulose acetate succinate (HPMCAS) types L, M and H and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOL) were evaluated by in vitro supersaturation studies regarding their anti-precipitant ability on the poorly soluble drug candesartan cilexetil (CC) under two different media, including biorelevant conditions...
March 15, 2018: Carbohydrate Polymers
Canser Yilmaz Demir, Muhammet Eren Ersoz, Remzi Erten, Omer Faruk Kocak, Yilmaz Sultanoglu, Yildiray Basbugan
BACKGROUND: The purpose of this study was to compare the effects of oral enalapril, an angiotensin-converting enzyme inhibitor (ACE-I), oral candesartan, an angiotensin receptor blocker (ARB), and intralesional corticosteroid treatments in reducing scar formation. METHODS: Twenty male rabbits were divided into five study groups: A (sham), B (control), C (ACE-I), D (ARB) and E (intralesional corticosteroid). The rabbit ear hypertrophic scar model was used. The hypertrophic scars were photographed and analyzed with the program ImageJ quantitatively to determine the degree of collagen fibers...
April 2018: Aesthetic Plastic Surgery
Emil Trofimiuk, Przemysław Wielgat, Jan J Braszko
BACKGROUND: Candesartan is one of the standard antihypertensive drug belonging to AT1R angiotensin receptor blockers (ARBs) group. Beneficial effects of this drug in the treatment of hypertension are well recognized. In this study we tested a hypothesis that candesartan could alleviate age-related memory decline. METHODS: Aged and young rats have been treated with candesartan (0.1 mg kg-1) for 21 days and then underwent a battery of behavioral tests: for assessment of long-term memory (Passive avoidance test - PA), recognition memory (Object recognition test - OR), locomotor functions (Open field - OF) and anxiety behavior (Elevated plus maze - EPM)...
July 21, 2017: Pharmacological Reports: PR
Marta Kuczeriszka, Elzbieta Kompanowska-Jezierska, Janusz Sadowski, Minolfa Prieto, L Gabriel Navar
Background: Indirect evidence suggests that angiotensin 1-7 (Ang1-7) may counterbalance prohypertensive actions of angiotensin II (AngII), via activation of vascular and/or renal tubular receptors to cause vasodilation and natriuresis/diuresis. We examined if Ang1-7 would attenuate the development of hypertension, renal vasoconstriction and decreased natriuresis in AngII-infused rats and evaluated the mechanisms involved. Methods: AngII, alone or with Ang1-7, was infused to conscious Sprague-Dawley rats for 13 days and systolic blood pressure (SBP) and renal excretion were repeatedly determined...
January 10, 2018: American Journal of Hypertension
V I Podzolkov, N A Dragomiretskaya
We present in this paper modern views on components, physiological and pathophysiological effects of the renin-angiotensin system, pathways of its hyperactivation at various stages of the cardiovascular continuum. Special emphasis is made on angiotensin receptor blockers (sartans). Basing on results of analysis of randomized clinical trials of these agents we have outlined clinical situations in which prescription of one or another drug from this group is preferable. For patients with multiple risk factors of cardiovascular complications preferable agent is telmisartan, for patients with nephropathy - irbesartan, for survivors of acute myocardial infarction - valsartan, while for patients with clinical signs of chronic heart failure with low ejection fraction 3 agents can be designated as preferrable - losartan, valsartan, and candesartan...
October 2017: Kardiologiia
Philip Joseph, Eva Lonn, Jackie Bosch, Patricio Lopez, Jun Zhu, Matyas Keltai, Anthony Dans, Christopher Reid, Kamlesh Khunti, William Toff, Leopoldo Piegas, Jae-Hyung Kim, Balakumar Swaminathan, Michael Bohm, Salim Yusuf
BACKGROUND: It is unclear whether modifying cholesterol, blood pressure, or both affect erectile dysfunction. Also, there are concerns that erectile dysfunction is worsened by common medications used to treat these risk factors. In this study, we evaluated the effect of: (1) cholesterol-lowering with a statin; (2) pharmacologic blood pressure reduction; and (3) their combination, on erectile function. METHODS: A priori, this was a secondary analysis of the Heart Outcomes Prevention Evaluation-3 (HOPE-3) randomized controlled trial...
January 2018: Canadian Journal of Cardiology
Marta de Diego, Ricardo Godoy, Sigrid Mennickent, Carola Vergara, Daniel Miranda, Pía Navarro
Development, validation and comparison of two stability-indicating LC methods, one with photodiode array detector (DAD) and the other with evaporative light scattering detector (ELSD), were performed for simultaneous determination of candesartan cilexetil (CANC) and hydrochlorothiazide (HCTZ), in pharmaceutical samples. A RP-18 column (125 mm × 4 mm, 5 μm) was used for separation of CANC, HCTZ and its major degradation products, using acetonitrile and phosphate buffer (pH 6.0) for DAD method and acetonitrile and water with acetic acid and triethylamine (pH 4...
December 11, 2017: Journal of Chromatographic Science
Michael J Haas, Marilu Jurado-Flores, Ramadan Hammoud, Victoria Feng, Krista Gonzales, Luisa Onstead-Haas, Arshag D Mooradian
BACKGROUND: Endothelial cell dysfunction in diabetes is involved in the pathogenesis and progression of premature atherosclerosis. High-dextrose has been shown to induce both oxidative stress and endoplasmic reticulum stress in cultured human coronary artery endothelial cells (HCAEC). STUDY QUESTION: To determine whether or not several classes of cardioprotective drugs inhibit proinflammatory cytokine expression by HCAEC. MEASURES AND OUTCOMES: To determine the effects of high dextrose on expression of proinflammatory cytokines by HCAEC, cells were treated with either 5...
November 27, 2017: American Journal of Therapeutics
Heba A Ahmed, Tauheed Ishrat, Bindu Pillai, Kristopher M Bunting, Ashni Patel, Almira Vazdarjanova, Jennifer L Waller, Ali S Arbab, Adviye Ergul, Susan C Fagan
Growing evidence suggests that renin angiotensin system (RAS) modulators support cognitive function in various animal models. However, little is known about their long-term effects on the brain structure in aged hypertensive animals with chronic cerebral hypoperfusion as well as which specific domains of cognition are most affected. Therefore, in the current study we examined the effects of Candesartan and Compound 21 (C21) (RAS modulators) on aspects of cognition known to diminish with advanced age and accelerate with hypertension and vascular disease...
December 8, 2017: Behavioural Brain Research
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