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https://www.readbyqxmd.com/read/28928054/effect-of-the-antidiabetic-agent-pioglitazone-on-bone-metabolism-in-rats
#1
Junkichi Kanda, Nobuo Izumo, Yoshiko Kobayashi, Kenji Onodera, Taketoshi Shimakura, Noriaki Yamamoto, Hideaki E Takahashi, Hiroyuki Wakabayashi
Thiazolidinediones (TZDs) are synthetic peroxisome proliferator-activated receptor gamma (PPARγ) agonists used as therapy for type 2 diabetes. However, clinical studies reported that the therapeutic modulation of PPARγ activity using TZDs may induce negative effects on bone metabolism. This study aimed to evaluate the effect of the TZD pioglitazone on bone metabolism in rats. Male Wistar rats were treated orally with pioglitazone 5 or 20 mg/kg daily for 24 weeks. Bone strength was evaluated using a 3-point bending method, and bone histomorphometry was analyzed...
August 26, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28920418/myogenic-satellite-cells-differentiation-with-linolenic-and-retinoic-and-thiazolidenediones-from-prepubertal-korean-black-goat
#2
Sugathan Subi, Sungjin Lee, Supriya Shiwani, Naresh Kumar Singh
Objective: Myogenic satellite cells were isolated from semitendinosus muscle of prepubertal Korean black goat to observe the differential effect of linolenic and retinoic acid in thepresence of thiazolidinediones and also to observe the production insulin sensitive preadipocyte. Methods: Cells were characterized for its stemness with CD 34, CD 13, CD 106, CD44, Vimentin surface markers using flow cytometry. Cells characterized themselves to possess significant (p<0...
September 18, 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/28872778/effects-of-thiazolidinedione-in-patients-with-active-bladder-cancer
#3
Roger Li, Michael J Metcalfe, J E Ferguson Rd, Sharada Mokkapati, Graciela M Nogueras González, Colin P Dinney, Neema Navai, David J McConkey, Sunil K Sahai, Ashish M Kamat
OBJECTIVE: To examine the influence of perioperative thiazolidinedione (TZD) on cancer-specific outcomes in patients undergoing radical cystectomy (RC) for urothelial carcinoma (UC). DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort of 173 diabetic patients undergoing RC from 2005 to 2010 was identified. Of those, 53 were on TZD treatment at the time of surgery, with 33 patients taking pioglitazone. Baseline clincopathologic characteristics, as well as cancer specific survival (CSS), recurrence free survival (RFS), and overall survival (OS) were compared between the patients on and off of TZD at the time of RC...
September 5, 2017: BJU International
https://www.readbyqxmd.com/read/28854981/rosiglitazone-increases-endothelial-cell-migration-and-vascular-permeability-through-akt-phosphorylation
#4
Yun Hyi Ku, Bong-Jun Cho, Min Joo Kim, Soo Lim, Young Joo Park, Hak C Jang, Sung Hee Choi
BACKGROUND: Thiazolidinediones (TZDs), peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists, exhibit anti-inflammatory and antioxidant properties and inhibit endothelial inflammation and dysfunction, which is anti-atherogenic. However, fluid retention, which may lead to congestive heart failure and peripheral edema, is also a concern, which may result from endothelial cell leakage. In the current study, we examined the effects of PPAR-γ agonists on vascular endothelial cell migration and permeability in order to determine its underlying mechanisms...
August 30, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28853334/identification-of-novel-ppar%C3%AE-%C3%AE-dual-agonists-by-virtual-screening-admet-prediction-and-molecular-dynamics-simulations
#5
Xin Liu, Zhi Jing, Wen-Qing Jia, Shu-Qing Wang, Ying Ma, Wei-Ren Xu, Xian-Chao Cheng
PPARα and PPARγ have been the most widely studied Peroxisome Proliferator-Activated Receptor (PPAR) subtypes due to their important roles in regulating glucose, lipids and cholesterol metabolism. By combining the lowering serum triglyceride levels benefit of PPARα agonists (such as fibrates) with the glycemic advantages of the PPARγ agonists (such as TZD), the dual PPAR agonists approach can both improve the metabolic effects and minimize the side effects caused by either agent alone, and hence has become a promising strategy for designing effective drugs against type-2 diabetes...
August 30, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28816105/thiazolidinedione-drugs-in-the-treatment-of-type-2-diabetes-mellitus-past-present-and-future
#6
Melissa A Davidson, Donald R Mattison, Laurent Azoulay, Daniel Krewski
Thiazolidinedione (TZD) drugs used in the treatment of type 2 diabetes mellitus (T2DM) have proven effective in improving insulin sensitivity, hyperglycemia, and lipid metabolism. Though well tolerated by some patients, their mechanism of action as ligands of peroxisome proliferator-activated receptors (PPARs) results in the activation of several pathways in addition to those responsible for glycemic control and lipid homeostasis. These pathways, which include those related to inflammation, bone formation, and cell proliferation, may lead to adverse health outcomes...
August 17, 2017: Critical Reviews in Toxicology
https://www.readbyqxmd.com/read/28781774/level-of-dietary-energy-and-2-4-thiazolidinedione-alter-molecular-and-systemic-biomarkers-of-inflammation-and-liver-function-in-holstein-cows
#7
Afshin Hosseini, Mustafa Salman, Zheng Zhou, James K Drackley, Erminio Trevisi, Juan J Loor
BACKGROUND: The objective of the study was to evaluate the effect of overfeeding a moderate energy diet and a 2,4-thiazolidinedione (TZD) injection on blood and hepatic tissue biomarkers of lipid metabolism, oxidative stress, and inflammation as it relates to insulin sensitivity. RESULTS: Fourteen dry non-pregnant cows were fed a control (CON) diet to meet 100% of NRC requirements for 3 wk, after which half of the cows were assigned to a moderate-energy diet (OVE) and half of the cows continued on CON for 6 wk...
2017: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/28780749/testing-the-ability-of-rhodanine-and-2-4-thiazolidinedione-to-interact-with-the-human-pancreatic-alpha-amylase-electron-density-descriptors-complement-molecular-docking-qm-and-qm-mm-dynamics-calculations
#8
Rajendran Niranjana Devi, Maria G Khrenova, Samuel Israel, Chellam Anzline, Andrey A Astakhov, Vladimir G Tsirelson
A combined molecular docking, QM, and QM/MM dynamics modeling complemented with electron-density based descriptors computed at the B3LYP/6-311G++(d,p) level of theory have been carried out in order to understand the ability of the drugs rhodanine (RD) and 2,4-thiazolidinedione (TZD) in the effective treatment of type 2 diabetes mellitus. The global HOMO/LUMO descriptors provided just a very rough estimate of the chemical reactivity of both molecules, while the features of electron density studied in terms of its Laplacian and electrostatic potential allowed identifying the local electron rich/poor sites which were associated with the regions of electrophilic/nucleophilic attacks in RD and TZD...
September 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28769000/a-novel-bongkrekic-acid-analog-mediated-modulation-of-the-size-of-lipid-droplets-evidence-for-the-appearance-of-smaller-adipocytes
#9
Hiroyuki Okazaki, Shuso Takeda, Hiroyuki Ishii, Yukimi Takemoto, Satoshi Fujita, Masaki Suyama, Kenji Matsumoto, Mitsuru Shindo, Hironori Aramaki
Thiazolidinediones (TZDs) are known as peroxisome proliferator-activated receptor γ (PPARγ) activators, and are used in the treatment of diabetes. Although the usefulness of TZDs has been demonstrated, some of their side effects are becoming an obstacle to their clinical applicability; edema is known to be evoked by the "structural characteristics" of TZD, but not by the PPARγ activation. Thus, novel therapeutic modalities (i.e., non-TZD-type PPARγ activators) having different structures to those of TZDs are desired...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28757415/study-of-the-interactions-between-edaglitazone-and-ciglitazone-with-ppar%C3%AE-and-their-antiplatelet-profile
#10
Camila Muñoz-Gutiérrez, Cesar Sepúlveda, Julio Caballero, Iván Palomo, Eduardo Fuentes
Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcription factor with an important role in lipid metabolism, inflammation and cardiovascular diseases. PPARγ ligands have inhibitory effects on platelet aggregation via the cAMP pathway, which may confer them a protective cardioprotective role. Edaglitazone and Ciglitazone are two chemically-similar thiazolidinedione (TZD) drugs that have been described as potent PPARγ agonists; however, Edaglitazone is over 100 times more potent than Ciglitazone...
October 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28740504/2-4-thiazolidinedione-treatment-improves-the-innate-immune-response-in-dairy-goats-with-induced-subclinical-mastitis
#11
Fernanda Rosa, Johan S Osorio, Erminio Trevisi, Francisco Yanqui-Rivera, Charles T Estill, Massimo Bionaz
Mastitis is a major disease in dairy cows resulting in significant economic losses. In vitro works suggest that ruminants peroxisome proliferator-activated receptor gamma (PPARγ) can aid in improving the response to mastitis and can control milk fat synthesis. The objectives of the present experiment were to test if treatment with the putative PPARγ agonist 2,4-thiazolidinedione (TZD) improves (1) the response to subclinical mastitis and (2) milk fat production. Lactating goats received daily injections of 8 mg/kg BW of TZD or saline for 3 weeks...
2017: PPAR Research
https://www.readbyqxmd.com/read/28730750/improving-type-2-diabetes-mellitus-glycaemic-outcomes-is-possible-without-spending-more-on-medication-lessons-from-the-uk-national-diabetes-audit
#12
Adrian H Heald, Mark Livingston, Nagaraj Malipatil, Michal Becher, Joyce Craig, Mike Stedman, Anthony A Fryer
OBJECTIVES: There is continuing discussion globally about how to optimise outcomes for type 2 diabetes (T2DM) patients. In the UK, national (NICE) guidance was updated in 2016 (NG28). We aimed to determine the factors at a GP practice level that relate to glycaemic control outcome. METHODS: Data was accessed from 4,050 GP practices (GPP) (50% of total) covering 1.6 million T2DM patients in the UK National Diabetes Audit 2013-14 and 2014-15. This reported T2DM population characteristics, services and outcomes, including % total glycaemic control (TGC) (at 67...
July 20, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28716729/study-of-new-interactions-of-glitazone-s-stereoisomers-and-the-endogenous-ligand-15d-pgj2-on-six-different-ppar-gamma-proteins
#13
Samuel Álvarez-Almazán, Martiniano Bello, Feliciano Tamay-Cach, Marlet Martínez-Archundia, Diana Alemán-González-Duhart, José Correa-Basurto, Jessica Elena Mendieta-Wejebe
Diabetes mellitus is a chronic disease characterized by hyperglycemia, insulin resistance and hyperlipidemia. Glitazones or thiazolidinediones (TZD) are drugs that act as insulin-sensitizing agents whose molecular target is the peroxisome proliferator-activated receptor gamma (PPARγ). The euglycemic action of TZD has been linked with the induction of type 4 glucose transporter. However, it has been shown that the effect of TZD depends on the specific stereoisomer that interacts with PPARγ. Therefore, this work is focused on exploring the interactions and geometry adopted by glitazone's stereoisomers and one endogenous ligand on different conformations of the six crystals of the PPARγ protein using molecular docking and molecular dynamics (MD) simulations accompanied by the MMGBSA approach...
July 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28705641/design-synthesis-biological-evaluation-and-molecular-modelling-studies-of-novel-diaryl-substituted-pyrazolyl-thiazolidinediones-as-potent-pancreatic-lipase-inhibitors
#14
Sridhar S N C, Deendyal Bhurta, Dharmvir Kantiwal, Ginson George, Vikramdeep Monga, Atish T Paul
A series of novel diaryl substituted pyrazolyl 2,4-thiazolidinediones were synthesized via reaction of appropriate pyrazolecarboxaldehydes with 2,4-thiazolidinedione (TZD) and nitrobenzyl substituted 2,4-thiazolidinedione. The resulting compounds were screened in vitro for pancreatic lipase (PL) inhibitory activity. Two assay protocols were performed viz., methods A and B using p-nitrophenyl butyrate and tributyrin as substrates, respectively. Compound 11e exhibited potent PL inhibitory activity (IC50=4.81µM and Xi50=10...
August 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28685995/meta-analysis-and-critical-review-on-the-efficacy-and-safety-of-alpha-glucosidase-inhibitors-in-asian-and-non-asian-populations
#15
Xueying Gao, Xiaoling Cai, Wenjia Yang, Yifei Chen, Xueyao Han, Linong Ji
AIMS: To evaluate the efficacy and safety of alpha glucosidase inhibitors (AGI) in Asian and non-Asian type 2 diabetic patients. MATERIALS AND METHODS: Studies were identified through a literature search of MEDLINE, EMBASE, and other databases until December 2016. All statistical analyses were conducted in Review Manager statistical software by computing the weighted mean difference (WMD) or odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of 67 studies were included...
July 7, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28659972/discovery-of-novel-insulin-sensitizers-promising-approaches-and-targets
#16
REVIEW
Yadan Chen, Haiming Ma, Dasheng Zhu, Guowei Zhao, Lili Wang, Xiujuan Fu, Wei Chen
Insulin resistance is the undisputed root cause of type 2 diabetes mellitus (T2DM). There is currently an unmet demand for safe and effective insulin sensitizers, owing to the restricted prescription or removal from market of certain approved insulin sensitizers, such as thiazolidinediones (TZDs), because of safety concerns. Effective insulin sensitizers without TZD-like side effects will therefore be invaluable to diabetic patients. The specific focus on peroxisome proliferator-activated receptor γ- (PPARγ-) based agents in the past decades may have impeded the search for novel and safer insulin sensitizers...
2017: PPAR Research
https://www.readbyqxmd.com/read/28645575/prediction-of-drug-induced-immune-mediated-hepatotoxicity-using-hepatocyte-like-cells-derived-from-human-embryonic-stem-cells
#17
Dong Eon Kim, Mi-Jin Jang, Young Ran Kim, Joo-Young Lee, Eun Byul Cho, Eunha Kim, Yeji Kim, Mi Young Kim, Won-Il Jeong, Seyun Kim, Yong-Mahn Han, Seung-Hyo Lee
Drug-induced liver injury (DILI) is a leading cause of liver disease and a key safety factor during drug development. In addition to the initiation events of drug-specific hepatotoxicity, dysregulated immune responses have been proposed as major pathological events of DILI. Thus, there is a need for a reliable cell culture model with which to assess drug-induced immune reactions to predict hepatotoxicity for drug development. To this end, stem cell-derived hepatocytes have shown great potentials. Here we report that hepatocyte-like cells derived from human embryonic stem cells (hES-HLCs) can be used to evaluate drug-induced hepatotoxic immunological events...
July 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28636360/proneurogenic-effects-of-trazodone-in-murine-and-human-neural-progenitor-cells
#18
Valeria Bortolotto, Francesca Mancini, Giorgina Mangano, Rita Salem, Er Xia, Erika Del Grosso, Michele Bianchi, Pier Luigi Canonico, Lorenzo Polenzani, Mariagrazia Grilli
Several antidepressants increase adult hippocampal neurogenesis (ahNG) in rodents, primates, and, potentially, humans. This effect may at least partially account for their therapeutic activity. The availability of antidepressants whose mechanism of action involves different neurotransmitter receptors represents an opportunity for increasing our knowledge on their distinctive peculiarities and for dissecting the contribution of receptor subtypes in ahNG modulation. The aim of this study was to evaluate, in vitro, the effects of the antidepressant trazodone (TZD) on ahNG by using primary cultures of murine adult hippocampal neural progenitor cells (ahNPCs) and human induced pluripotent stem cell (iPSC)-derived NPCs...
July 3, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28618987/synthesis-of-new-thiazolyl-coupled-pyrazoles-bearing-2-4-thiazolidinedionyl-pharmacophore-and-their-anti-inflammatory-and-antibacterial-evaluation
#19
Lalit Khillare, Manisha Bhosle, Mahendra Bhalerao, Kiran Kharat, Ramrao Mane
BACKGROUND: 2, 4-Thiazolidinedione (TZD), pyrazole and thiazole heterocyclic rings exhibit wide range of pharmacological activities. Medicinal chemists use these heterocyclic moieties as scaffolds in drug designing and discovery. The existing medicaments, celecoxib and meloxicam, used for treating inflammation and pain are having, pyrazole and thiazole, respectively as a key scaffolds. Pyrazoles coupled with 2, 4-thiazolidinediones may display enhanced anti inflammatory activity. With this hope the title work was carried...
June 16, 2017: Anti-inflammatory & Anti-allergy Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28611274/meta-analysis-of-randomized-controlled-trials-of-pharmacologic-agents-in-non-alcoholic-steatohepatitis
#20
Adnan Said, Ahmed Akhter
BACKGROUND: Currently, there is no standardized treatment regimen for non-alcoholic steatohepatitis. AIM: We performed a metaanalysis of high quality randomized controlled trials that evaluated treatment response to metformin, thiazolidinediones (TZDs), and vitamin E in adult patients with non-alcoholic steatohepatitis. Outcome measures were improvement in liver histology, biochemical, and anthropometric measures. MATERIAL AND METHODS: Nine trials met inclusion criteria (3 with TZD, 3 with Metformin, 2 with Vitamin E and 1 with both TZD and Vitamin E...
August 1, 2017: Annals of Hepatology
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