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https://www.readbyqxmd.com/read/29675426/a-novel-method-for-drug-screen-to-regulate-g-protein-coupled-receptors-in-the-metabolic-network-of-alzheimer-s-disease
#1
Yang Li, Wei Zheng, Wuyun Qiqige, Shujuan Cao, Jishou Ruan, Yanping Zhang
Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder and the pathogenesis of AD is poorly understood. G protein-coupled receptors (GPCRs) are involved in numerous key AD pathways and play a key role in the pathology of AD. To fully understand the pathogenesis of AD and design novel drug therapeutics, analyzing the connection between AD and GPCRs is of great importance. In this paper, we firstly build and analyze the AD-related pathway by consulting the KEGG pathway of AD and a mass of literature and collect 25 AD-related GPCRs for drug discovery...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29673890/efficacy-and-safety-of-fixed-dose-combination-therapy-with-telmisartan-and-rosuvastatin-in-korean-patients-with-hypertension-and-dyslipidemia-telsta-yu-telmisartan-rosuvastatin-from-yuhan-a-multicenter-randomized-4-arm-double-blind-placebo-controlled-phase
#2
Gyu Chul Oh, Jung-Kyu Han, Ki Hoon Han, Min-Su Hyon, Joon Hyung Doh, Moo Hyun Kim, Jin-Ok Jeong, Jang-Ho Bae, Sang Hyun Kim, Byung-Su Yoo, Sang Hong Baek, Moo-Yong Rhee, Sang-Hyun Ihm, Jung Hoon Sung, Young Jin Choi, Soo-Joong Kim, Kyung-Soon Hong, Byoung Kwon Lee, JangHyun Cho, Eun Seok Shin, Jay Young Rhew, Hyunsu Kim, Hyo-Soo Kim
PURPOSE: Hypertension and dyslipidemia are 2 risk factors of cardiovascular disease that often present simultaneously. Traditionally, treatment of these multiple conditions required separate medications for each disease, which may result in poor compliance and thus lead to possible treatment failure. Fixed-dose combination (FDC) therapy with a single pill may be a solution in these situations. METHODS: This multicenter, 8-week, randomized, double-blind, Phase III study evaluated the efficacy and safety of FDC treatment with telmisartan (80 mg) and rosuvastatin calcium (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia...
April 16, 2018: Clinical Therapeutics
https://www.readbyqxmd.com/read/29663195/which-target-blood-pressure-in-year-2018-evidence-from-recent-clinical-trials
#3
REVIEW
Sondre Heimark, Julian E Mariampillai, Krzysztof Narkiewicz, Peter M Nilsson, Sverre E Kjeldsen
The Systolic Blood Pressure Intervention Trial (SPRINT) suggested a favourable effect of lowering blood pressure to < 120/80 mmHg in high-risk hypertensive patients; however, new American guidelines in 2017 have not followed SPRINT but lowered its recommended treatment target to < 130/80 mmHg. We aimed to review the latest research from large randomised controlled trials and observational analyses in order to investigate the evidence for new treatment targets. We assessed recent data from the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD) study, the International Verapamil-Trandolapril Study (INVEST), the Telmisartan, Ramipril or Both in Patients at High Risk for Vascular Events trial (ONTARGET)/the Telmisartan Randomised AssessmenNt Study in aCE iNtolerant participants with cardiovascular Disease (TRANSCEND) study and The Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study...
April 16, 2018: High Blood Pressure & Cardiovascular Prevention: the Official Journal of the Italian Society of Hypertension
https://www.readbyqxmd.com/read/29617054/activation-of-voltage-gated-sodium-current-and-inhibition-of-erg-mediated-potassium-current-caused-by-telmisartan-an-antagonist-of-angiotensin-ii-type-1-receptor-in-hl-1-atrial-cardiomyocytes
#4
Wei-Ting Chang, Sheng-Nan Wu
Telmisartan (TEL) is a non-peptide blocker of angiotensin II type-1 (AT1 ) receptor. However, the mechanisms through which this drug interacts directly with ion currents in hearts remain largely unclear. Herein, we aim to investigate the effects of TEL the on ionic currents and membrane potential of murine HL-1 cardiomyocytes. In whole-cell recordings, addition of TEL stimulated the peak and late components of voltage-gated Na+ currents (IN a ) with different potencies. The EC50 values required to achieve the stimulatory effect of this drug on peak and late IN a were 0...
April 4, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29589977/a-meta-analysis-of-antihypertensive-effect-of-telmisartan-versus-candesartan-in-patients-with-essential-hypertension
#5
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
https://www.readbyqxmd.com/read/29579636/determination-of-dexmedetomidine-by-uhplc-ms-ms-and-its-application-to-evaluate-the-effect-of-dexmedetomidine-concentration-on-the-target-controlled-infusion-concentration-of-propofol
#6
Zhuoling Zheng, Shuyu Zhang, Wudi Ma, Lingyi Zhang, Ling Huang, Wenqi Huang, Min Huang, Zhongxing Wang, Jiali Li
The combination of dexmedetomidine (DEX) and propofol (PPF) is extensively used in the field of anaesthesiology. This study aimed to develop and validate a rapid, simple and sensitive ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination of DEX in human plasma. The method was applied to evaluate the effect of DEX concentration on the target-controlled infusion (TCI) concentration of PPF. Analytes were separated on a Waters XTERRA® MS C18 column with a mobile phase of acetonitrile-methanol-water containing 0...
May 30, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29570771/the-non-biphenyl-tetrazole-at1-receptor-blocker-eprosartan-is-a-unique-and-robust-inverse-agonist-of-the-active-state-of-at1-receptor
#7
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
https://www.readbyqxmd.com/read/29559771/pharmacokinetic-and-bioequivalence-study-of-a-telmisartan-s-amlodipine-fixed-dose-combination-ckd-828-formulation-and-coadministered-telmisartan-and-s-amlodipine-in-healthy-subjects
#8
Woo Youl Kang, Sook Jin Seong, Boram Ohk, Mi-Ri Gwon, Bo Kyung Kim, Sookie La, Hyun-Ju Kim, Seungil Cho, Young-Ran Yoon, Dong Heon Yang, Hae Won Lee
Purpose: A new fixed-dose combination (FDC) formulation of telmisartan 80 mg and S-amlodipine 5 mg (CKD-828) has been developed to increase convenience (as only one tablet is required per day) and improve treatment compliance. Methods: The pharmacokinetic characteristics and tolerability of an FDC of telmisartan and S-amlodipine were compared to those after coadministration of the individual agents in this randomized, open-label, single-dose, two-way, four-period, crossover study...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29557807/telmisartan-improves-insulin-resistance-a-meta-analysis
#9
Yan Wang, Shun Qiao, De-Wu Han, Xin-Ren Rong, Yi-Xiao Wang, Jing-Jing Xue, Jing Yang
BACKGROUND: Diabetes mellitus, metabolic syndrome, and other obesity-related diseases are characterized by insulin resistance (IR) as a common pathophysiological change and are closely related to cardiovascular disease, which seriously threaten human health. Telmisartan belongs to a group of drugs called angiotensin II receptor antagonists (ARBs) and it can partially activate peroxisome proliferator-activated receptors. Animal experiments have confirmed that telmisartan can regulate glucose and lipid metabolism, and improve IR...
March 16, 2018: American Journal of Therapeutics
https://www.readbyqxmd.com/read/29552215/telmisartan-inhibits-nsclc-a549-cell-proliferation-and-migration-by-regulating-the-pi3k-akt-signaling-pathway
#10
Suolin Zhang, Yayan Wang
Expression of angiotensin II (Ang II), a key biological peptide in the renin-angiotensin system, is closely associated with the occurrence and development of cancer. Ang II binds two receptor subtypes, the Ang II type 1 receptor (AT1R) and the AT2R, to mediate a series of biological effects. Telmisartan, a specific AT1R blocker, has been reported to have potential as an anticancer drug for treating renal cancer. In the present study, whether telmisartan had an effect on non-small cell lung cancer (NSCLC) cell proliferation and migration was investigated...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29515275/telmisartan-and-esculetin-combination-ameliorates-type-2-diabetic-cardiomyopathy-by-reversal-of-h3-h2a-and-h2b-histone-modifications
#11
Almesh Kadakol, Vajir Malek, Santosh Kumar Goru, Anuradha Pandey, Anil Bhanudas Gaikwad
OBJECTIVES: Although cardioprotective effects of telmisartan are well explored, its effects on epigenetic alterations associated with type 2 diabetic (T2D) cardiomyopathy remain unmapped. Thus, the present study was designed to evaluate the potential of esculetin and telmisartan combination to reverse histone posttranslational modifications (PTMs) in curbing T2D cardiomyopathy. MATERIALS AND METHODS: T2D was induced by high-fat diet feeding along with low dose of streptozotocin (35 mg/kg, I...
September 2017: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/29513155/evaluation-of-orally-administered-telmisartan-for-the-reduction-of-indirect-systolic-arterial-blood-pressure-in-awake-clinically-normal-cats
#12
Amanda E Coleman, Scott A Brown, Marcus Stark, Lawrence Bryson, Alicia Zimmerman, Tanja Zimmering, Anne M Traas
Objectives The aim of this study was to compare the effects of multiple once- or twice-daily oral dosage rates of the angiotensin II, type-1 receptor blocker, telmisartan (TEL), or placebo (PLA) on indirect systolic arterial blood pressure (SBP) in awake, clinically normal cats. Methods Utilizing an incomplete crossover design and following a 14 day acclimation period, 28 healthy laboratory cats were randomized to undergo treatment with three of the following 14 day treatment protocols, each separated by a 1 week washout period: oral PLA q24h, oral TEL at a dosage of 1, 1...
March 1, 2018: Journal of Feline Medicine and Surgery
https://www.readbyqxmd.com/read/29470359/cd44-deficiency-in-mice-protects-the-heart-against-angiotensin-ii-induced-cardiac-fibrosis
#13
Li-Wang Yang, Dong-Ze Qin, Erskine James, Robert J McKallip, Ning-Ping Wang, Wei-Wei Zhang, Rong-Hua Zheng, Qing-Hua Han, Zhi-Qing Zhao
This study tested the hypothesis that CD44 is involved in development of cardiac fibrosis via angiotensin II (Ang II) AT1 receptor stimulated TNFα/NFκB/IκB signaling pathways. Study was conducted in C57BL/6 wild type and CD44 knockout mice subjected to Ang II infusion (1000 ng/kg/min) using osmotic minipumps up to 4 weeks or with gastric gavage administration of the AT1 receptor blocker, telmisartan at a dose of 10 mg/kg/day. Results indicated that Ang II enhances expression of the AT1 receptor, TNFα, NFκB and CD44 as well as downregulates IκB...
February 21, 2018: Shock
https://www.readbyqxmd.com/read/29468289/effect-of-cryopreservation-on-enzyme-and-transporter-activities-in-suspended-and-sandwich-cultured-rat-hepatocytes
#14
Janneke Keemink, Neel Deferm, Tom De Bruyn, Patrick Augustijns, Thomas Bouillon, Pieter Annaert
Freshly-isolated rat hepatocytes are commonly used as tools for hepatic drug disposition. From an ethical point of view, it is important to maximize the use of isolated hepatocytes by cryopreservation. The present study compared overall hepatocyte functionality as well as activity of the organic anion transporting polypeptide (Oatp), multidrug resistance-associated protein 2 (Mrp2), and UDP-glucuronosyltransferase 1 (Ugt1), in in vitro models established with cryopreserved and freshly-isolated hepatocytes. A similar culture time-dependent decline in cellular functionality, as assessed by urea production, was observed in sandwich-cultured hepatocytes (SCH) obtained from freshly-isolated and cryopreserved cells...
February 21, 2018: AAPS Journal
https://www.readbyqxmd.com/read/29466880/telmisartan-reverses-antiretroviral-induced-adipocyte-toxicity-and-insulin-resistance-in-vitro
#15
Sudeep P Pushpakom, Antonysunil Adaikalakoteswari, Andrew Owen, David J Back, Gyanendra Tripathi, Sudhesh Kumar, Philip McTernan, Munir Pirmohamed
BACKGROUND: Antiretroviral therapy in HIV-positive patients leads to insulin resistance which is central to the pathogenesis of various metabolic abnormalities and cardiovascular disease seen in this patient group. We have investigated the dose-response relationship of telmisartan, an antihypertensive, on adipocytes in vitro in order to determine whether it may have metabolic beneficial effects. METHODS: Using in vitro chronic toxicity models (3T3-F442A murine and primary human adipocytes), we evaluated the effects of different concentrations of telmisartan on adipocyte differentiation and adipogenic gene expression using lipid accumulation assays and real-time polymerase chain reaction, respectively...
February 1, 2018: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/29464572/brain-renin-angiotensin-system-blockade-attenuates-methamphetamine-induced-hyperlocomotion-and-neurotoxicity
#16
Linhong Jiang, Ruiming Zhu, Qian Bu, Yan Li, Xue Shao, Hui Gu, Jueying Kong, Li Luo, Hailei Long, Wei Guo, Jingwei Tian, Yinglan Zhao, Xiaobo Cen
Methamphetamine (METH) abuse has become a major public health concern worldwide without approved pharmacotherapies. The brain renin-angiotensin system (RAS) is involved in the regulation of neuronal function as well as neurological disorders. Angiotensin II (Ang II), which interacts with Ang II type 1 receptor (AT1 -R) in the brain, plays an important role as a neuromodulator in dopaminergic transmission. However, the role of brain RAS in METH-induced behavior is largely unknown. Here, we revealed that repeated METH administration significantly upregulated the expression of AT1 -R in the striatum of mice, but downregulated dopamine D3 receptor (D3R) expression...
February 20, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29421561/inhibition-of-tumor-promoting-stroma-to-enforce-subsequently-targeting-at1r-on-tumor-cells-by-pathological-inspired-micelles
#17
Yun Zhu, Lijuan Wen, Shihong Shao, Yanan Tan, Tingting Meng, Xiqin Yang, Yupeng Liu, Xuan Liu, Hong Yuan, Fuqiang Hu
Cancer associated fibroblasts (CAFs) are the most abundant, genetically stable stroma cells and localize near blood vessels within "finger-like" collagen-rich stroma, which lead to restrained drug transport in dense stroma instead of tumor cells inside tumor mass, especially for targeting micelles. Meanwhile, the bioactive cytokines secreted by stroma cells result in microenvironment mediated drug resistance (TMDR). Hence, a biologically inspired Telmisartan (Tel) grafting glycolipid micelles (Tel-CSOSA) are constructed, which can sequentially target angiotensin II type I receptor (AT1R) overexpressed on both CAFs and tumor cells...
January 18, 2018: Biomaterials
https://www.readbyqxmd.com/read/29414040/identification-and-characterization-of-the-druggable-kinase-targets-of-olmesartan-and-its-analogues-from-a-systematic-kinase-chemical-interaction-profile-in-atherosclerosis
#18
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
https://www.readbyqxmd.com/read/29404063/development-and-validation-of-a-high-throughput-lc-ms-ms-method-for-simultaneous-quantitation-of-pioglitazone-and-telmisartan-in-rat-plasma-and%C3%A2-its%C3%A2-application-to-a-pharmacokinetic-study
#19
Pinaki Sengupta, Bappaditya Chatterjee, Uttam Kumar Mandal, Bapi Gorain, Tapan Kumar Pal
Management of cardiovascular risk factors in diabetes demands special attention due to their co-existence. Pioglitazone (PIO) and telmisartan (TLM) combination can be beneficial in effective control of cardiovascular complication in diabetes. In this research, we developed and validated a high throughput LC-MS/MS method for simultaneous quantitation of PIO and TLM in rat plasma. This developed method is more sensitive and can quantitate the analytes in relatively shorter period of time compared to the previously reported methods for their individual quantification...
December 2017: Journal of Pharmaceutical Analysis
https://www.readbyqxmd.com/read/29401318/telmisartan-does-not-improve-lymph-node-or-adipose-tissue-fibrosis-more-than-continued-art-alone
#20
Netanya S Utay, Douglas W Kitch, Eunice Yeh, Carl J Fichtenbaum, Michael M Lederman, Jacob D Estes, Claire Deleage, Clara Magyar, Scott D Nelson, Karen L Klingman, Barbara Bastow, Amneris E Luque, Grace A McComsey, Daniel C Douek, Judith S Currier, Jordan E Lake
Background: Fibrosis in lymph nodes may limit CD4+ T-cell recovery and lymph node and adipose tissue fibrosis may contribute to inflammation and comorbidities despite antiretroviral therapy (ART). We hypothesized that the angiotensin receptor blocker and PPAR-γ agonist telmisartan would decrease lymph node or adipose tissue fibrosis in treated HIV-1 infection. Methods: In this 48-week, randomized-controlled trial, adults continued suppressive ART and received telmisartan or no drug...
February 1, 2018: Journal of Infectious Diseases
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