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https://www.readbyqxmd.com/read/29930330/lysyl-oxidase-like-2-inhibition-ameliorates-glomerulosclerosis-and-albuminuria-in-diabetic-nephropathy
#1
Stefanie Stangenberg, Sonia Saad, Heidi C Schilter, Amgad Zaky, Anthony Gill, Carol A Pollock, Muh Geot Wong
Diabetic nephropathy is characterised by the excessive amount of extracellular matrix in glomeruli and tubulointerstitial space. Lysyl oxidase-like 2 (LOXL2) is elevated in renal fibrosis and known to play key roles in ECM stabilisation by facilitating collagen cross-links, epithelial to mesenchymal transition and myofibroblast activation. Thus, targeting LOXL2 may prove to be a useful strategy to prevent diabetic nephropathy. We explored the renoprotective effect of a selective small molecule LOXL2 inhibitor (PXS-S2B) in a streptozotocin-induced diabetes model...
June 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29929000/telmisartan-generates-ros-dependent-upregulation-of-death-receptor-5-to-sensitize-trail-in-lung-cancer-via-inhibition-of-autophagy-flux
#2
Mohammad Rasheduzzaman, Ji-Hong Moon, Ju-Hee Lee, Uddin Md Nazim, Sang-Youel Park
Telmisartan broadly used for the treatment of hypertension that is also known for its anticancer properties. TRAIL has the potential to kill tumor cells with minimal toxicity in normal cells by binding to death receptors, DR4 and DR5. Unfortunately, these TRAIL-death receptors have failed as most human cancers are resistant to TRAIL-mediated apoptosis. In this study, we evaluated telmisartan as a novel TRAIL-DR5-targeting agent with the aim of rendering TRAIL-based cancer therapies more active. Herein, we demonstrated that telmisartan could sensitize TRAIL and enhance NSCLC tumor cell death...
June 18, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29925421/s-amlodipine-plus-chlorthalidone-vs-s-amlodipine-plus-telmisartan-in-hypertensive-patients-unresponsive-to-amlodipine-monotherapy-study-protocol-for-a-randomized-controlled-trial
#3
Sang-Ho Jo, Sung-Ji Park, Eung Ju Kim, Soo-Joong Kim, Hyun-Jae Cho, Jong-Min Song, Jinho Shin, Jin Joo Park, Joon-Han Shin, Kyoo-Rok Han, Dong-Ju Choi
BACKGROUND: The efficacy of a combination of a calcium channel blocker (CCB) plus chlorthalidone (diuretic) versus a CCB plus an angiotensin receptor blocker (ARB) in patients not responding to CCB monotherapy has not been evaluated previously. We plan to compare the efficacy and safety of S-amlodipine (CCB) plus chlorthalidone versus S-amlodipine plus telmisartan (ARB) combinations among hypertension patients unresponsive to amlodipine monotherapy. METHODS/DESIGN: This study is a prospective, randomized, double-blind, multicenter, parallel, non-inferiority phase 4 study...
June 20, 2018: Trials
https://www.readbyqxmd.com/read/29910501/severe-angioedema-of-laryngeal-inlet-in-a-woman-receiving-telmisartan-therapy-undergoing-breast-conservation-surgery
#4
Bikram Kishore Behera, Satyajeet Misra, Madhabananda Kar
No abstract text is available yet for this article.
May 2018: Indian Journal of Anaesthesia
https://www.readbyqxmd.com/read/29909460/modulation-of-brain-ace-and-ace2-may-be-a-promising-protective-strategy-against-cerebral-ischemia-reperfusion-injury-an-experimental-trial-in-rats
#5
Maha Mohammed Abdel-Fattah, Basim Anwar Shehata Messiha, Ahmed Mohamed Mansour
The brain renin-angiotensin system (RAS) is considered a crucial regulator for physiological homeostasis and disease progression. We evaluated the protective effects of the angiotensin receptor blocker (ARB) telmisartan and the angiotensin-converting enzyme 2 (ACE2) activator xanthenone on experimental cerebral ischemia/reperfusion (I/R) injury. Rats were divided into a sham control, a cerebral I/R control, a standard treatment (nimodipine, 10 mg/kg/day, 15 days, p.o.), three telmisartan treatments (1, 3, and 10 mg/kg/day, 15 days, p...
June 17, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29888284/observations-of-the-effects-of-angiotensin-ii-receptor-blocker-on-angiotensin-ii-induced-morphological-and-mechanical-changes-in-renal-tubular-epithelial-cells-using-atomic-force-microscopy
#6
Jin Sug Kim, Gi-Ja Lee, Tae Won Lee, Chun Gyoo Ihm, Yu Ho Lee, Yang Gyun Kim, Ju-Young Moon, Sang Ho Lee, Ji-Hye Kim, Sung-Wook Kang, Su-Jin Chae, Hun-Kuk Park, Kyung Hwan Jeong
Objective: Angiotensin II (Ang II) plays a profibrotic role in the kidneys. Although many pathways of Ang II have been discovered, the morphological and mechanical aspects have not been well investigated. We observed the changes in tubular epithelial cells (TECs) after Ang II treatment with or without Ang II receptor blockers (ARBs) using atomic force microscopy (AFM). Methods: TECs were stimulated with Ang II with or without telmisartan, PD123319, and blebbistatin...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29886423/upward-shift-and-steepening-of-the-blood-pressure-response-to-exercise-in-hypertensive-subjects-at-high-altitude
#7
Sergio Caravita, Andrea Faini, Claudia Baratto, Grzegorz Bilo, Josè Luis Macarlupu, Morin Lang, Miriam Revera, Carolina Lombardi, Francisco C Villafuerte, Piergiuseppe Agostoni, Gianfranco Parati
BACKGROUND: Acute exposure to high-altitude hypobaric hypoxia induces a blood pressure rise in hypertensive humans, both at rest and during exercise. It is unclear whether this phenomenon reflects specific blood pressure hyperreactivity or rather an upward shift of blood pressure levels. We aimed at evaluating the extent and rate of blood pressure rise during exercise in hypertensive subjects acutely exposed to high altitude, and how these alterations can be counterbalanced by antihypertensive treatment...
June 9, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29879670/analysis-of-pharmaceutical-biodegradation-of-wwtp-sludge-using-composting-and-identification-of-certain-microorganisms-involved-in-the-process
#8
María Iranzo, Miguel Gamón, Rafael Boluda, Salvador Mormeneo
Pharmaceuticals (PhCs) are organic contaminants that have been detected in wastewater, surface water, and soils throughout the world. The presence of 10 commonly used PhCs in Spain (azithromycin, benzylpenicillin, citalopram, fluconazole, fluoxetine, ibuprofen, irbesartan, olanzapine, telmisartan, and venlafaxine) was analysed at four wastewater treatment plants, and the changes in their concentrations during treatment were assessed. Although certain some PhCs were degraded in the treated water, their presence in sewage sludge increased in all cases...
June 4, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29873709/achieved-diastolic-blood-pressure-and-pulse-pressure-at-target-systolic-blood-pressure-120-140-mmhg-and-cardiovascular-outcomes-in-high-risk-patients-results-from-ontarget-and-transcend-trials
#9
Michael Böhm, Helmut Schumacher, Koon K Teo, Eva Lonn, Felix Mahfoud, Johannes F E Mann, Giuseppe Mancia, Josep Redon, Roland Schmieder, Michael Weber, Karen Sliwa, Bryan Williams, Salim Yusuf
Aims: Current guidelines of hypertensive management recommend upper limits for systolic (SBP) and diastolic blood pressure (DBP). J-curve associations of BP with risk exist for some outcomes suggesting that lower limits of DBP goals may also apply. We examined the association between mean attained DBP and cardiovascular (CV) outcomes in patients who achieved an on-treatment SBP in the range of 120 to <140 mmHg in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) and Telmisartan Randomized AssessmeNt Study in ACE iNtolerant participants with cardiovascular Disease (TRANSCEND) trials on patients with high CV risk...
June 4, 2018: European Heart Journal
https://www.readbyqxmd.com/read/29867471/pharmacogenetic-aspects-of-the-interaction-of-at1-receptor-antagonists-with-atp-binding-cassette-transporter-abcg2
#10
Anne Ripperger, Anna Krischer, Dina Robaa, Wolfgang Sippl, Ralf A Benndorf
The ATP-binding cassette transporter ABCG2 (BCRP and MXR) is involved in the absorption, distribution, and elimination of numerous drugs. Thus, drugs that are able to reduce the activity of ABCG2, e.g., antihypertensive AT1 receptor antagonists (ARBs), may cause drug-drug interactions and compromise drug safety and efficacy. In addition, genetic variability within the ABCG2 gene may influence the ability of the transporter to interact with ARBs. Thus, the aim of this study was to characterize the ARB-ABCG2 interaction in the light of naturally occurring variations (F489L, R482G) or amino acid substitutions with in silico -predicted relevance for the ARB-ABCG2 interaction (Y469A; M483F; Y570A)...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29851104/development-and-validation-of-rapid-and-sensitive-lc-methods-with-pda-and-fluorescence-detection-for-determination-of-piribedil-in-rat-plasma-and-brain-tissues-and-their-pharmacokinetic-application
#11
Chandra Teja Uppuluri, Avantika V Dalvi, B Ekta Prasanthi, Punna Rao Ravi
Simple, selective and sensitive high-performance liquid chromatographic (HPLC) bioanalytical methods using fluorescence (FL) and photodiode array (PDA) detectors were developed and validated for determination of Piribedil (PBD), an anti-Parkinson's drug, in rat plasma and brain samples, with Telmisartan as internal standard (IS). Protein precipitation technique was used to extract PBD from both the biological matrices. Chromatographic separation was achieved on a Phenomenex Kinetex C18 end-capped column (250 × 4...
May 31, 2018: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/29805801/hypertension-treatment-in-patients-with-metabolic-syndrome-and-or-type-2-diabetes-mellitus-analysis-of-the-therapy-effectivity-and-the-therapeutic-inertia-in-outpatient-study
#12
Štefan Farský, Andrea Strišková, Marián Borčin
We have analysed the database of 1,595 consecutive patients visiting our department of cardiology and internal medicine clinic in 2005-2014. The analysis included 13,990 visit records, and the average number of visits per patient was 8.5 ± 7.0. Our goals were to evaluate the effectivity of hypertension treatment as for drug choice, decrease of sBP and dBP associated with a certain drug, a drug combination, and therapeutic inertia in patients with metabolic syndrome and/or diabetes mellitus. The final number of patients for analysis who fulfilled the inclusion criteria for interpenetration of both diagnostic circles was 570...
2018: Cardiology Research and Practice
https://www.readbyqxmd.com/read/29800852/trace-organic-chemical-pollutants-from-the-lake-waters-of-san-pablo-city-philippines-by-targeted-and-non-targeted-analysis
#13
Ian Ken D Dimzon, Ann Selma Morata, Janine Müller, Roy Kristian Yanela, Stephan Lebertz, Heike Weil, Teresita R Perez, Jutta Müller, Fabian M Dayrit, Thomas P Knepper
More than half of the freshwater lakes in the Philippines are small with surface areas of <2 km2 . The dynamics in these lakes are different from those in the bigger lakes. This study was conducted to determine the organic pollutants and their sources in three of the seven lakes of San Pablo City in Laguna, Philippines: lakes Palakpakin, Sampaloc, and Pandin. Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography - Tandem Mass Spectrometry (LC-MS/MS) were used in the targeted and non-targeted analysis of the lake water samples...
May 22, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29785143/pilot-study-of-the-antifibrotic-effects-of-the-multikinase-inhibitor-pacritinib-in-a-mouse-model-of-liver-fibrosis
#14
Suliman Al-Fayoumi, Taishi Hashiguchi, Yuka Shirakata, John Mascarenhas, Jack W Singer
Background: Fibrotic diseases result from an exuberant response to chronic inflammation. Myelofibrosis is the end result of inflammation in bone, caused by an inflammatory process triggered by production of abnormal myeloid cells driven by mutations affecting the JAK-STAT pathway. Inflammatory cytokine overproduction leads to increased mesenchymal cell proliferation, culminating in fibrosis. Although JAK2 inhibitors, such as the JAK1/2 inhibitor ruxolitinib and the JAK2/FLT3/CSF1R/IRAK1 inhibitor pacritinib suppress abnormal clone expansion in myelofibrosis, ruxolitinib does not appear to prevent or reverse bone-marrow fibrosis in most patients...
2018: Journal of Experimental Pharmacology
https://www.readbyqxmd.com/read/29759885/terfenadone-is-a-strong-inhibitor-of-cyp2j2-present-in-the-human-liver-and-intestinal-microsomes
#15
Eunyoung Lee, Ju-Hyun Kim, Jong Cheol Shon, Zhexue Wu, Hyun Ji Kim, Minsik Gim, Taeho Lee, Kwang-Hyeon Liu
Cytochrome P450 2J2 (CYP2J2) is involved in the metabolism of drugs, including albendazole, astemizole, ebastine, and endogenous substrates. In a previous study, we used recombinant CYP2J2 and determined whether danazol, hydroxyebastine, telmisartan, and terfenadone inhibited CYP2J2 by using four representative CYP2J2 substrates, namely albendazole, astemizole, ebastine, and terfenadine. In this study, we evaluated the inhibitory potential of these four chemicals on human liver and intestinal microsomes, which are commonly used in a reaction phenotyping study...
March 15, 2018: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29759229/evaluation-of-polar-organic-chemical-integrative-and-hollow-fibre-samplers-for-the-determination-of-a-wide-variety-of-organic-polar-compounds-in-seawater
#16
Leire Mijangos, Haizea Ziarrusta, Ailette Prieto, Oihane Zugazua, Olatz Zuloaga, Maitane Olivares, Aresatz Usobiaga, Albrecht Paschke, Nestor Etxebarria
The calibration of two passive samplers for the determination of 20 emerging organic compounds in seawater is described in this work: i) a new version of polar organic chemical integrative sampler (POCIS) containing 100 mg of mixed-mode anion exchanger (Strata X-AW) and 100 mg of polymeric HLB (Plexa) sorbent materials and using a highly porous Nylon membrane (30-μm pore size) and ii) polyethersulfone (PES) hollow fibre. Among the studied contaminants, herbicides, hormones, life style products (stimulants and artificial sweeteners), industrial chemicals (corrosion inhibitor and fluorinated compounds), personal care products and several pharmaceuticals were included...
August 1, 2018: Talanta
https://www.readbyqxmd.com/read/29746136/relative-activity-factor-raf-based-scaling-of-uptake-clearance-mediated-by-organic-anion-transporting-polypeptide-oatp-1b1-and-oatp1b3-in-human-hepatocytes
#17
Saki Izumi, Yoshitane Nozaki, Hiroyuki Kusuhara, Koichiro Hotta, Toshiki Mochizuki, Takafumi Komori, Kazuya Maeda, Yuichi Sugiyama
In vitro-in vivo extrapolation based on uptake clearance determined in human hepatocytes has been used to predict in vivo hepatic clearance of organic anion transporting polypeptide (OATP) substrates. This study evaluated the relative activity factor (RAF) approach to extrapolate active uptake clearance in transporter-transfected cell systems (CLuptake ) to that in human hepatocyte suspensions (PSinf,act ). RAF values for OATP1B1 and OATP1B3 were determined in two batches of cryopreserved human hepatocytes using estrone-3-sulfate and cholecystokinin octapeptide as reference substrates, respectively...
May 10, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29746133/in-vitro-dissolution-as-a-tool-for-formulation-selection-telmisartan-two-step-ivivc
#18
Alejandro Ruiz-Picazo, Mª Teresa Martinez-Martinez, Sarin Colon-Useche, Ramon Iriarte, Barbara Sanchez-Dengra, Marta Gonzalez-Alvarez, Alfredo Garcia-Arieta, Isabel Gonzalez Alvarez, Marival Bermejo
The main objective of this investigation was to develop an exploratory two-step level A IVIVC for three Telmisartan oral immediate release formulations, the reference product Micardis and two generic formulations (X1 and X2). Correlation was validated with a third test formulation Y1. Experimental solubility and permeability data was obtained to confirm that Telmisartan is a class II compound under the Biopharmaceutic Classification System. BE studies plasma profiles were combined using a previously published reference scaling procedure...
May 10, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29731445/synthesis-characterization-and-antihypertensive-activity-of-2-phenyl-substituted-benzimidazoles
#19
Muhammad Tariq Khan, Muhammad Tahir Razi, Syed Umer Jan, Muhammad Mukhtiar, Rahman Gul, - IzharUllah, Abid Hussain, Asif Mehmood Hashmi, Muhammad Taufiq Ahmad, Nisar Ahmed Shahwani, Imran Rabbani
Hypertension is one of cardiovascular disease that is not sufficiently prevented and controlled at both hospital and community levels. Hypertension resulted in significant morbidity and mortality. The benz-imidazole ring is very important pharmacophore in modern drug discovery. The substituted benzimidazoles are the important for medicinal research. Researchers have reported that substituted Benzimidazoles are the structural isosteres of nucleotides, and easily allow them to interact with the different biopolymers, possess pharmacological activity especially antihypertensive activity...
May 2018: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29721772/telmisartan-attenuates-hydrogen-peroxide-induced-apoptosis-in-differentiated-pc12-cells
#20
Guan Tao Du, Xuan Ke, Guo Liang Meng, Guang Jun Liu, Hui Ying Wu, Jin Hong Gong, Xiao Dan Qian, Jin Luo Cheng, Hao Hong
The present study investigated the protective actions of telmisartan, an angiotensin II type 1 receptor blocker (ARBs), against the cell apoptosis induced by exposure to hydrogen peroxide (H2 O2 ) in differentiated PC12 cells. Preincubation of PC12 cells with telmisartan prevented H2 O2 -induced cytotoxicity as indicated by increased MTT (3,(4,5-dimethylthiazole-2-yl)2,5-diphenyl-tetrazolium bromide) reduction, decreased lactate dehydrogenase (LDH) release, and improved morphological changes. Hoechst 33,258 staining showed that telmisartan markedly reduced shrunken nuclei of the cells, and Western blot analysis indicated that telmisartan significantly attenuated caspase-3 activity, as indicated by decreased ratio of cleaved Caspase-3 to its precursor and increased ratio of Bcl-2/Bax...
May 3, 2018: Metabolic Brain Disease
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