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https://www.readbyqxmd.com/read/28523719/cardiovascular-events-associated-with-second-line-anti-diabetes-treatments-analysis-of-real-world-korean-data
#1
K H Ha, B Kim, H Choi, D J Kim, H C Kim
AIM: To compare the risks of cardiovascular disease (CVD) and all-cause mortality associated with sulfonylurea (SU), dipeptidyl peptidase-4 inhibitor (DPP4i) and thiazolidinedione (TZD) as add-on medications to metformin (MET) therapy in people with Type 2 diabetes. METHODS: We identified 40 263 individuals who used SU (n = 11 582), DPP4i (n = 26 623) or TZD (n = 2058) in addition to MET between January 2013 and June 2015 from the database of the Korean National Health Insurance, the single-payer healthcare system in South Korea...
May 19, 2017: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/28506609/ageing-kinetics-and-strength-of-airborne-particle-abraded-3y-tzp-ceramics
#2
Jasna Cotič, Peter Jevnikar, Andraž Kocjan
OBJECTIVE: The combined effects of alumina airborne-particle abrasion and prolonged in vitro ageing on the flexural strength of 3Y-TZP ceramic have been studied. The aim was to identify the different effects on the surface and subsurface regions that govern the performance of this popular bioceramic known for its susceptibility to low-temperature degradation (LTD). METHODS: As-sintered or airborne-particle abraded 3Y-TZP discs were subjected to ageing at 134°C for up to 480h...
May 12, 2017: Dental Materials: Official Publication of the Academy of Dental Materials
https://www.readbyqxmd.com/read/28499821/x-ray-crystal-structure-of-rivoglitazone-bound-to-ppar%C3%AE-and-ppar-subtype-selectivity-of-tzds
#3
Harinda Rajapaksha, Harpreet Bhatia, Kate Wegener, Nikolai Petrovsky, John B Bruning
Thiazolidinedione (TZD) compounds targeting the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR) demonstrate unique benefits for the treatment of insulin resistance and type II diabetes. TZDs include rosiglitazone, pioglitazone and rivoglitazone, with the latter being the most potent. The TZDs are only marginally selective for the therapeutic target PPARγ as they also activate PPARα and PPARδ homologues to varying degrees, causing off-target effects. While crystal structures for TZD compounds in complex with PPARγ are available, minimal structural information is available for TZDs bound to PPARα and PPARδ...
May 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28469599/the-role-of-thyrotropin-receptor-activation-in-adipogenesis-and-modulation-of-fat-phenotype
#4
Mohd Shazli Draman, Michael Stechman, David Scott-Coombes, Colin M Dayan, Dafydd Aled Rees, Marian Ludgate, Lei Zhang
Evidence from clinical and experimental data suggests that thyrotropin receptor (TSHR) signaling is involved in energy expenditure through its impact on white adipose tissue (WAT) and brown adipose tissue (BAT). TSHR expression increases during mesenchymal stem cell (MSC) differentiation into fat. We hypothesize that TSHR activation [TSHR*, elevated thyroid-stimulating hormone, thyroid-stimulating antibodies (TSAB), or activating mutation] influences MSC differentiation, which contributes to body composition changes seen in hypothyroidism or Graves' disease (GD)...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28438542/identification-of-low-micromolar-dual-inhibitors-for-aldose-reductase-alr2-and-poly-adp-ribose-polymerase-parp-1-using-structure-based-design-approach
#5
Navriti Chadha, Om Silakari
Clinical studies have revealed that diabetic retinopathy is a multifactorial disorder. Moreover, studies also suggest that ALR2 and PARP-1 co-occur in retinal cells, making them appropriate targets for the treatment of diabetic retinopathy. To find the dual inhibitors of ALR2 and PARP-1, the structure based design was carried out in parallel for both the target proteins. A series of novel thiazolidine-2,4-dione (TZD) derivatives were therefore rationally designed, synthesized and their in vitro inhibitory activities against ALR2 and PARP-1 were evaluated...
April 13, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28384299/in-depth-study-of-dna-binding-of-cys2his2-finger-domains-in-testis-zinc-finger-protein
#6
Chun-Chi Chou, Shu-Yi Wei, Yuan-Chao Lou, Chinpan Chen
Previously, we identified that both fingers 1 and 2 in the three Cys2His2 zinc-finger domains (TZD) of testis zinc-finger protein specifically bind to its cognate DNA; however, finger 3 is non-sequence-specific. To gain insights into the interaction mechanism, here we further investigated the DNA-binding characteristics of TZD bound to non-specific DNAs and its finger segments bound to cognate DNA. TZD in non-specific DNA binding showed smaller chemical shift perturbations, as expected. However, the direction of shift perturbation, change of DNA imino-proton NMR signal, and dynamics on the 15N backbone atom significantly differed between specific and non-specific binding...
2017: PloS One
https://www.readbyqxmd.com/read/28383181/effects-of-silica-coating-by-physical-vapor-deposition-and-repeated-firing-on-the-low-temperature-degradation-and-flexural-strength-of-a-zirconia-ceramic
#7
Tutku Cakir-Omur, Rifat Gozneli, Yasemin Ozkan
PURPOSE: To examine the application of physical vapor deposition (PVD) silica coating as an approach to retard low temperature degradation (LTD) for dental applications. Accelerated aging characteristics of heat- and surface-treated zirconia material were also investigated by exposing specimens to hydrothermal treatment. MATERIALS AND METHODS: The specimens (90 disc-shaped specimens [15 mm ×1.2 mm]) were divided into 9 groups (n = 10) according to the test protocol: Ctrl, control (no surface treatment); Ag, autoclave aging; GrAg, grinding + aging; SiAg, silica coating + aging; GrSiAg, grinding + silica coating + aging; 3FAg, 3-time firing + aging; Gr3FAg, grinding + 3-time firing + aging; 5FAg, 5-time firing + aging; Gr5FAg, grinding + 5-time firing + aging...
April 6, 2017: Journal of Prosthodontics: Official Journal of the American College of Prosthodontists
https://www.readbyqxmd.com/read/28381265/thiazolidinedione-use-and-atrial-fibrillation-in-diabetic-patients-a-meta-analysis
#8
Zhiwei Zhang, Xiaowei Zhang, Panagiotis Korantzopoulos, Konstantinos P Letsas, Gary Tse, Mengqi Gong, Lei Meng, Guangping Li, Tong Liu
BACKGROUND: Accumulating evidence suggests that thiazolidinediones (TZDs) may exert protective effects in atrial fibrillation (AF). The present meta-analysis investigated the association between TZD use and the incidence of AF in diabetic patients. METHODS: Electronic databases were searched until December 2016. Of the 346 initially identified records, 3 randomized clinical trials (RCTs) and 4 observational studies with 130,854 diabetic patients were included in the final analysis...
April 5, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28348577/deciphering-the-roles-of-thiazolidinediones-and-ppar%C3%AE-in-bladder-cancer
#9
REVIEW
Melody Chiu, Lucien McBeth, Puneet Sindhwani, Terry D Hinds
The use of thiazolidinedione (TZD) therapy in type II diabetic patients has proven useful in the lowering of blood glucose levels. However, recent investigations have shown that there may be potential health concerns associated, including the risk of developing bladder cancer as well as complications in the cardiovasculature. TZDs are ligands for the nuclear receptor PPARγ, and activation causes lipid uptake and insulin sensitization, both of which are critical processes for diabetic patients whose bodies are unable to utilize insulin effectively...
2017: PPAR Research
https://www.readbyqxmd.com/read/28314484/impact-of-health-policy-and-practice-on-finding-the-best-fit-for-patients-with-type-2-diabetes-after-metformin-failure-croatian-pilot-study
#10
Maja Cigrovski Berković, Davorka Herman Mahečić, Marina Gradišer, Ines Bilić-Ćurčić
AIM: We assessed the impact of clinical practice and health policy on the choice and efficacy of different second-line therapies for the treatment of type 2 diabetes (T2DM) after failure of metformin. METHODS: This retrospective database analysis included 200 patients with a follow-up period of 6 months. The primary end-point was achievement of HbA1c <7% and fasting (FBG) and postprandial glucose levels (PPG) <7.2mmol/L and <10mmol/L, respectively after three and six months of different add-on treatments...
June 2017: Primary Care Diabetes
https://www.readbyqxmd.com/read/28302016/validation-of-tzd-scaffold-as-potential-aris-pharmacophore-modelling-atom-based-3d-qsar-and-docking-studies
#11
Lalita Dahiya, Manoj Kumar Mahapatra, Ramandeep Kaur, Vipin Kumar, Manoj Kumar
Metabolic disorders associated with diabetic patients are a serious concern. Aldose reductase (ALR2) has been identified as first rate-limiting enzyme in the polyol pathway which catalyzes the reduction of glucose to sorbitol. It represents one of the validated targets to develop potential new chemical entities for the prevention and subsequent progression of microvascular diabetic complications. In order to further understand the intricate structural prerequisites of molecules to act as ALR2 inhibitors, ligand-based pharmacophore model, atom-based 3D-QSAR and structure based drug design studies have been performed on a series of 2,4-thiazolidinedione derivatives with ALR2 inhibitory activity...
March 15, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28248890/effect-of-contraindicated-drugs-for-heart-failure-on-hospitalization-among-seniors-with-heart-failure-a-nested-case-control-study
#12
Catherine Girouard, Jean-Pierre Grégoire, Paul Poirier, Jocelyne Moisan
Little is known about the effect of nonsteroidal anti-inflammatory drugs (NSAIDs), thiazolidinediones (TZDs), nifedipine and nondihydropyridine calcium channel blockers (CCBs) usage on the risk of all-cause hospitalization among seniors with heart failure (HF). We assessed the risk of all-cause hospitalization associated with exposure to each of these drug classes, in a population of seniors with HF.Using the Quebec provincial databases, we conducted a nested case-control study in a population of individuals aged ≥65 with a first HF diagnosis between 2000 and 2009...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28202347/in-silico-design-chemical-synthesis-and-toxicological-evaluation-of-1-3-thiazolidine-2-4-dione-derivatives-as-ppar%C3%AE-agonists
#13
Diana Alemán-González-Duhart, Feliciano Tamay-Cach, José Correa-Basurto, Itzia Irene Padilla-Martínez, Samuel Álvarez-Almazán, Jessica Elena Mendieta-Wejebe
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors involved in the metabolism of lipids and carbohydrates. The exogenous ligands of these receptors are thiazolidinediones (TZDs), which are used to treat type 2 diabetes mellitus (DM2). However, drugs from this group produce adverse effects such as hepatic steatosis. Hence, the aim of this work was to design a set of small molecules that can activate the γ isoform of PPARs while minimizing the adverse effects. The derivatives were designed containing the polar head of TZD and an aromatic body, serving simultaneously as the body and tail...
February 12, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28195389/no-increased-risk-of-cardiovascular-events-in-older-adults-initiating-dipeptidyl-peptidase-4-inhibitors-vs-therapeutic-alternatives
#14
Mugdha Gokhale, John B Buse, Michele Jonsson Funk, Jennifer Lund, Virginia Pate, Ross J Simpson, Til Stürmer
AIM: To compare the cardiovascular (CV) risk associated with dipeptidyl peptidase-4 (DPP-4) inhibitors relative to sulphonylureas (SUs) and thiazolidinediones (TZDs). METHODS: During 2007 to 2013, using Medicare data for beneficiaries aged >65 years, we identified the following 2 cohorts of new-users, who had not been exposed to the drugs being compared in the 6 months before initiation: (1) DPP-4 inhibitor vs SU initiators and (2) DPP-4 inhibitor vs TZD initiators...
February 14, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28193552/rational-design-and-synthesis-of-some-ppar-%C3%AE-agonists-substituted-benzylideneamino-benzylidene-thiazolidine-2-4-diones
#15
Santosh S Chhajed, Shital Chaskar, Sanjay K Kshirsagar, G M Animeshchandra Haldar, Debarshi Kar Mahapatra
The peroxisome proliferator activator receptor-γ (PPAR-γ) remained the most successful target for management of diabetes mellitus. The present work endeavors rational designing of some novel PPAR-γ agonists bearing benzylideneamino-benzylidene-thiazolidine-2,4-dione scaffold. The research involved virtual screening of 37 different molecules by molecular docking studies performed by Molecular Design Suite (MDS) into the ligand binding domain of PPAR-γ receptor to explore the binding affinity and conformations of the molecules...
April 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28165718/modification-of-the-orthosteric-ppar%C3%AE-covalent-antagonist-scaffold-yields-an-improved-dual-site-allosteric-inhibitor
#16
Richard Brust, Hua Lin, Jakob Fuhrmann, Alice Asteian, Theodore M Kamenecka, Douglas J Kojetin
GW9662 and T0070907 are widely used commercially available irreversible antagonists of peroxisome proliferator-activated receptor gamma (PPARγ). These antagonists covalently modify Cys285 located in an orthosteric ligand-binding pocket embedded in the PPARγ ligand-binding domain and are used to block binding of other ligands. However, we recently identified an alternate/allosteric ligand-binding site in the PPARγ LBD to which ligand binding is not inhibited by these orthosteric covalent antagonists. Here, we developed a series of analogs based on the orthosteric covalent antagonist scaffold with the goal of inhibiting both orthosteric and allosteric cellular activation of PPARγ by MRL20, an orthosteric agonist that also binds to an allosteric site...
February 16, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28128331/identification-of-a-novel-selective-ppar%C3%AE-ligand-with-a-unique-binding-mode-and-improved-therapeutic-profile-in-vitro
#17
Wei Yi, Jingjing Shi, Guanguan Zhao, X Edward Zhou, Kelly Suino-Powell, Karsten Melcher, H Eric Xu
Thiazolidinediones (TZD) function as potent anti-diabetic drugs through their direct action on the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ), but their therapeutic benefits are compromised by severe side effects. To address this concern, here we developed a potent "hit" compound, VSP-51, which is a novel selective PPARγ-modulating ligand with improved therapeutic profiles in vitro compared to the multi-billion dollar TZD drug rosiglitazone (Rosi). Unlike Rosi, VSP-51 is a partial agonist of PPARγ with improved insulin sensitivity due to its ability to bind PPARγ with high affinity without stimulating adipocyte differentiation and the expression of adipogenesis-related genes...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28028073/thiazolidinediones-are-associated-with-a-decreased-risk-of-atrial-fibrillation-compared-with-other-antidiabetic-treatment-a-nationwide-cohort-study
#18
Jannik Langtved Pallisgaard, Tommi Bo Lindhardt, Laila Staerk, Jonas Bjerring Olesen, Christian Torp-Pedersen, Morten Lock Hansen, Gunnar Hilmar Gislason
AIM: The aim of this study was to investigate the association between thiazolidinediones (TZDs) vs. other antidiabetic drugs and risk of atrial fibrillation (AF) in diabetic patients. METHOD AND RESULTS: Diabetes mellitus (diabetes) increases the risk of AF by approximately 34%. TZD is an insulin sensitizer that also has anti-inflammatory effects, which might decrease the risk of AF compared with other antidiabetic drugs. We used data from the Danish nationwide registries to study 108 624 patients with diabetes and without prior AF who were treated with metformin or sulfonylurea as first-line drugs...
November 8, 2016: European Heart Journal. Cardiovascular Pharmacotherapy
https://www.readbyqxmd.com/read/27997588/protective-effects-of-vildagliptin-against-pioglitazone-induced-bone-loss-in-type-2-diabetic-rats
#19
Young Sil Eom, A-Ryeong Gwon, Kyung Min Kwak, Ju-Young Kim, Seung Hee Yu, Sihoon Lee, Yeun Sun Kim, Ie Byung Park, Kwang-Won Kim, Kiyoung Lee, Byung-Joon Kim
Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model...
2016: PloS One
https://www.readbyqxmd.com/read/27995594/liraglutide-versus-sglt-2-inhibitors-in-people-with-type-2-diabetes-a-network-meta-analysis
#20
Maria Lorenzi, Uffe Jon Ploug, Jakob Langer, Rasmus Skovgaard, Michael Zoratti, Jeroen Jansen
INTRODUCTION: For people with type 2 diabetes (T2DM) inadequately controlled with oral antidiabetic drugs (OADs), evidence from both randomized controlled trials (RCTs) and real-world studies has demonstrated that treatment intensification with liraglutide offers effective glycemic control, weight reduction, and a lower risk of hypoglycemia compared to treatment intensification with insulin or additional OADs. Sodium glucose cotransporter 2 (SGLT-2) inhibitors are a new class of OADs that have also been shown to be effective in T2DM patients inadequately controlled with OADs...
February 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
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