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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
#1
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
#2
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
#3
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
#4
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...
July 28, 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
#5
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
#6
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
#7
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 14, 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
#8
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...
June 28, 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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28597936/the-beneficial-metabolic-effects-of-insulin-sensitizers-are-not-attenuated-by-mitochondrial-pyruvate-carrier-2-hypomorphism
#15
Patrick A Vigueira, Kyle S McCommis, Wesley T Hodges, George G Schweitzer, Serena L Cole, Lalita Oonthonpan, Eric B Taylor, William G McDonald, Rolf F Kletzien, Jerry R Colca, Brian N Finck
What is the central question of this study? The antidiabetic effects of thiazolidinedione (TZD) drugs may be mediated in part by a molecular interaction with the constituent proteins of the mitochondrial pyruvate carrier complex (MPC1 and MPC2). We examined the ability of a mutant mouse strain expressing an N-terminal truncation of MPC2 (Mpc2Δ16 mice) to respond to TZD treatment. What is the main finding and its importance? The response of Mpc2Δ16 mice to TZD treatment was not significantly different from that of wild-type C57BL6/J control animals, suggesting that the 16 N-terminal amino acids of MPC2 are dispensable for the effects of TZD treatment...
June 9, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28589493/a-randomized-placebo-controlled-trial-evaluating-the-safety-and-efficacy-of-adding-omarigliptin-to-antihyperglycemic-therapies-in-japanese-patients-with-type-2-diabetes-and-inadequate-glycemic-control
#16
Ira Gantz, Taro Okamoto, Yuka Ito, Asako Sato, Kotoba Okuyama, Edward A O'Neill, Samuel S Engel, Eseng Lai
INTRODUCTION: Daily dipeptidyl peptidase-4 (DPP-4) inhibitors are commonly used with other orally administered antihyperglycemic agents (AHA), as combination therapy, to treat Japanese patients with type 2 diabetes. When combination therapy is indicated, use of a once-weekly (q.w.) orally administered DPP-4 inhibitor might be an appropriate therapeutic option for some patients. METHODS: A 52-week trial was conducted to assess the safety and tolerability (primary objectives) and glycemic efficacy (secondary objectives) of the q...
August 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28548941/withdrawn-prognostic-role-of-anti-diabetic-drugs-in-pancreatic-cancer-a-systematic-review-and-meta-analysis
#17
Lei Zheng, Shinan Yin, Fenghua Yao, Hua Bai, Danqing Jing
Ahead of Print article withdrawn by publisher.
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28542373/comparative-effectiveness-of-oral-antidiabetic-drugs-in-preventing-cardiovascular-mortality-and-morbidity-a-network-meta-analysis
#18
Gyeongsil Lee, Seung-Won Oh, Seung-Sik Hwang, Ji Won Yoon, Sungchan Kang, Hee-Kyung Joh, Hyuktae Kwon, Jeehyun Kim, Danbee Park
In the Guidance for Industry from the Food and Drug Administration in 2008, excess cardiovascular risk should be ruled out in trials of all new antidiabetic drugs; however, relatively few studies have focused on cardiovascular safety with antidiabetic drug use. We aimed to examine mortality and cardiovascular risk using a network meta-analysis. We searched the Medline, Embase, Cochrane, and ClinicalTrials.gov registry databases in March 2016 to identify randomized controlled trials reporting cardiovascular risk with the following oral antidiabetic drugs: metformin, sulfonylureas, thiazolidinedione (TZD), dipeptidyl peptidase-4 (DPP4) inhibitors, and sodium-glucose co-transporter-2 (SGLT2) inhibitors...
2017: PloS One
https://www.readbyqxmd.com/read/28539218/switching-subtype-selectivity-fragment-replacement-strategy-affords-novel-class-of-peroxisome-proliferator-activated-receptor-%C3%AE-%C3%AE-ppar%C3%AE-%C3%AE-dual-agonists
#19
Ryuta Shioi, Shogo Okazaki, Tomomi Noguchi-Yachide, Minoru Ishikawa, Makoto Makishima, Yuichi Hashimoto, Takao Yamaguchi
Peroxisome proliferator-activated receptors (PPARs) are important drug targets for treatment of dyslipidemia, type 2 diabetes, cardiovascular disease, nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, and great efforts have been made to develop novel PPAR ligands. However, most existing PPAR ligands contain a carboxylic acid (CA) or thiazolidinedione (TZD) structure (acidic head group) that is essential for activity. We recently discovered non-CA/TZD class PPARα/δ partial agonists, which contain an acetamide moiety and adjacent methyl group, linked to a 1,2,4-oxadiazole ring ("fragment a")...
May 13, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28523719/cardiovascular-events-associated-with-second-line-anti-diabetes-treatments-analysis-of-real-world-korean-data
#20
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...
September 2017: Diabetic Medicine: a Journal of the British Diabetic Association
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