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Pioglitazone

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https://www.readbyqxmd.com/read/28528664/enhanced-lc-ms-ms-analysis-of-alogliptin-and-pioglitazone-in-human-plasma-applied-to-a-preliminary-pharmacokinetic-study
#1
Maha F Abdel-Ghany, Miriam F Ayad, Mariam M Tadros
A new fast LC-MS/MS method was developed for determination of alogliptin and pioglitazone in human plasma. Linearity ranges of 10-400ngmL(-1) for alogliptin and 25-2000ngmL(-1) for pioglitazone, were found to be suitable for their bioanalysis covering the Cmin and Cmax values of the drugs. Direct precipitation technique was used for simultaneous extraction of the drugs successfully from human plasma samples. Chromatographic separation was achieved on a BEH C18 column (50mm×2.1mm, 1.7μm) with 0.1% aqueous formic acid: acetonitrile (40:60, v/v) at a flow rate of 0...
April 26, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28528456/pharmacologic-treatment-of-dyslipidemia-in-diabetes-a-case-for-therapies-in-addition-to-statins
#2
REVIEW
Abeer Anabtawi, Patrick M Moriarty, John M Miles
PURPOSE OF REVIEW: The purpose of the study is to review the use of statins and the role of both non-statin lipid-lowering agents and diabetes-specific medications in the treatment of diabetic dyslipidemia. RECENT FINDINGS: Statins have a primary role in the treatment of dyslipidemia in people with type 2 diabetes, defined as triglyceride levels >200 mg/dl and HDL cholesterol levels <40 mg/dL. A number of clinical trials suggest that treatment with a fibrate may reduce cardiovascular events...
July 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28526834/the-transcription-factor-irf6-co-represses-ppar%C3%AE-mediated-cytoprotection-in-ischemic-cerebrovascular-endothelial-cells
#3
Rongzhong Huang, Zicheng Hu, Yuxing Feng, Lehua Yu, Xingsheng Li
Activation of peroxisome proliferator-activated receptor gamma (PPARγ) in the cerebrovascular endothelium is a key suppressor of post-stroke brain damage. However, the role of PPARγ's co-regulators during cerebral ischemia remains largely unknown. Here, we show that the transcription factor IRF6 is a novel PPARγ co-regulator that directly binds to and suppresses PPARγ activity in murine cerebrovascular endothelial cells. Moreover, IRF6 was also revealed to be a transcriptional target of PPARγ suppression, with PPARγ silencing significantly promoting IRF6 expression in cerebrovascular endothelial cells...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526426/the-effects-of-troglitazone-on-ampk-in-hepg2-cells
#4
Katherine M Allen, Kimberly A Coughlan, Fabliha N Mahmood, Rudy J Valentine, Neil B Ruderman, Asish K Saha
AMP-activated protein kinase (AMPK) is an enzyme crucial in cellular metabolism found to be inhibited in many metabolic diseases including type 2 diabetes. Thiazolidinediones (TZDs) are a class of anti-diabetic drug known to activate AMPK through increased phosphorylation at Thr(172), however there has been no research to date on whether they have any effect on inhibition of AMPK's lesser known site of inhibition, Ser(485/491). HepG2 cells were treated with troglitazone and phosphorylation of AMPK was found to increase at both Thr(172) and Ser(485) in a dose- and time-dependent manner...
May 16, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28526186/cardiovascular-protection-in-the-treatment-of-type-2-diabetes-a-review-of-clinical-trial-results-across-drug-classes
#5
Francesco Paneni, Thomas F Lüscher
Patients with type 2 diabetes (T2DM) have a significantly higher risk of developing cardiovascular disease (CVD)-namely myocardial infarction, heart failure, and stroke. Despite clear advances in the prevention and treatment of CVD, the impact of T2DM on CVD outcome remains high and continues to escalate. Available evidence indicates that the risk of macrovascular complications increases with the severity of hyperglycemia, thus suggesting that the relation between metabolic disturbances and vascular damage is approximately linear...
May 15, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28522196/impact-of-glucose-lowering-therapies-on-risk-of-stroke-in-type-2-diabetes
#6
REVIEW
F Bonnet, A J Scheen
Patients with type 2 diabetes (T2D) have an increased risk of stroke compared with people without diabetes. However, the effects of glucose-lowering drugs on risk of ischaemic stroke in T2D have been less extensively investigated than in coronary heart disease. Some evidence, including the UKPDS, has suggested a reduced risk of stroke with metformin, although the number of studies is limited. Inhibition of the KATP channels increases ischaemic brain lesions in animals. This is in agreement with a recent meta-analysis showing an increased risk of stroke with sulphonylureas vs...
May 15, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28521870/the-use-of-statins-alone-or-in-combination-with-pioglitazone-and-other-drugs-for-the-treatment-of-non-alcoholic-fatty-liver-disease-non-alcoholic-steatohepatitis-and-related-cardiovascular-risk-an-expert-panel-statement
#7
REVIEW
Vasilios G Athyros, Theodore K Alexandrides, Helen Bilianou, Evangelos Cholongitas, Michael Doumas, Emmanuel S Ganotakis, John Goudevenos, Moses S Elisaf, Georgios Germanidis, Olga Giouleme, Asterios Karagiannis, Charalambos Karvounis, Niki Katsiki, Vasilios Kotsis, Jannis Kountouras, Evangelos Liberopoulos, Christos Pitsavos, Stergios Polyzos, Loukianos S Rallidis, Dimitrios Richter, Apostolos G Tsapas, Alexandros D Tselepis, Konstantinos Tsioufis, Konstantinos Tziomalos, Themistoklis Tzotzas, Themistoklis G Vasiliadis, Charalambos Vlachopoulos, Dimitri P Mikhailidis, Christos Mantzoros
Non-alcoholic fatty liver disease (NAFLD), the most common liver disease, is characterized by accumulation of fat (>5% of the liver tissue), in the absence of alcohol abuse or other chronic liver diseases. It is closely related to the epidemic of obesity, metabolic syndrome or type 2 diabetes mellitus (T2DM). NAFLD can cause liver inflammation and progress to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis or hepatocellular cancer (HCC). Nevertheless, cardiovascular disease (CVD) is the most common cause of death in NAFLD/NASH patients...
June 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28514232/ppar%C3%AE-agonists-attenuate-trigeminal-neuropathic-pain
#8
Danielle N Lyons, Liping Zhang, Robert J Danaher, Craig S Miller, Karin N Westlund
The aim of this study is to investigate the role of peroxisome proliferator-activated receptor-gamma isoform (PPARγ), in trigeminal neuropathic pain utilizing a novel mouse trigeminal inflammatory compression (TIC) injury model. The study determined that the PPARγ nuclear receptor plays a significant role in trigeminal nociception transmission, evidenced by: (1) Intense PPARγ immunoreactivity is expressed 3 weeks after TIC nerve injury in the spinal trigeminal caudalis, the termination site of trigeminal nociceptive nerve fibers...
May 16, 2017: Clinical Journal of Pain
https://www.readbyqxmd.com/read/28509380/amyloid-is-essential-but-insufficient-for-alzheimer-causation-addition-of-subcellular-cofactors-is-required-for-dementia
#9
REVIEW
Jeffrey Fessel
OBJECTIVE: The aim of this study is to examine the hypotheses stating the importance of amyloid or of its oligomers in the pathogenesis of Alzheimer's disease (AD). METHODS: Published studies were examined. RESULTS: The importance of amyloid in the pathogenesis of AD is well established, yet accepting it as the main cause for AD is problematic, because amyloid-centric treatments have provided no clinical benefit and about one-third of cognitively normal, older persons have cerebral amyloid plaques...
May 16, 2017: International Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28507248/new-hope-for-people-with-dysglycemia-and-cardiovascular-disease-manifestations-reduction-of-acute-coronary-events-with-pioglitazone
#10
EDITORIAL
Lars Rydén, Linda Mellbin
No abstract text is available yet for this article.
May 16, 2017: Circulation
https://www.readbyqxmd.com/read/28499821/x-ray-crystal-structure-of-rivoglitazone-bound-to-ppar%C3%AE-and-ppar-subtype-selectivity-of-tzds
#11
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/28498501/ppar-gamma-agonist-pioglitazone-modifies-craving-intensity-and-brain-white-matter-integrity-in-patients-with-primary-cocaine-use-disorder-a-double-blind-randomized-controlled-pilot-trial
#12
Joy M Schmitz, Charles E Green, Khader M Hasan, Jessica Vincent, Robert Suchting, Michael F Weaver, F Gerard Moeller, Ponnada A Narayana, Kathryn A Cunningham, Kelly T Dineley, Scott D Lane
BACKGROUND AND AIMS: Pioglitazone (PIO), a potent agonist of PPAR-gamma, is a promising candidate treatment for cocaine use disorder (CUD). We tested the effects of PIO on targeted mechanisms relevant to CUD: cocaine craving and brain white matter (WM) integrity. Feasibility, medication compliance, and tolerability were evaluated. DESIGN: Two-arm double-blind randomized controlled proof-of-concept pilot trial of PIO or placebo (PLC). SETTING: Single-site outpatient treatment research clinic in Houston, Texas, USA...
May 12, 2017: Addiction
https://www.readbyqxmd.com/read/28494529/nash-therapy-omega-3-supplementation-vitamin-e-insulin-sensitizers-and-statin-drugs
#13
Stephen Caldwell
Non-alcoholic steatohepatitis (NASH) is the more aggressive form of non-alcoholic fatty liver disease (NAFLD). NASH can progress to hepatic fibrosis, cirrhosis, portal hypertension and primary liver cancer. Therapy is evolving with a substantial number of trials of promising new agents now in progress. In this article however, we will examine data for several older forms of therapy which have been fairly extensively studied over the years: Polyunsaturated Fatty Acid (PUFA) supplements, vitamin E, insulin sensitizing agents with a focus on pioglitazone and statin agents...
May 10, 2017: Clinical and Molecular Hepatology
https://www.readbyqxmd.com/read/28488008/ameliorating-the-effect-of-pioglitazone-on-lps-induced-inflammation-of-human-oligodendrocyte-progenitor-cells
#14
Maryam Peymani, Kamran Ghaedi, Motahare-Sadat Hashemi, Ali Ghoochani, Abbas Kiani-Esfahani, Mohammad Hossein Nasr-Esfahani, Hossein Baharvand
Oligodendrocyte progenitor cells (OPCs) are appropriate model cells for studying the progress of neurodegenerative disorders and evaluation of pharmacological efficacies of small molecules for treatment of these disorders. Here, we focused on the therapeutic role of Pioglitazone, which is a selective agonist of peroxisome proliferator-activated receptor gamma (PPARγ), a respective nuclear receptor in inflammatory responses. Human embryonic stem cell-derived OPCs were pretreated by Pioglitazone at differing concentrations...
May 9, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28486596/troglitazone-inhibits-bile-acid-amidation-a-possible-risk-factor-for-liver-injury
#15
Eiichiro Ogimura, Tetsuya Nakagawa, Jiro Deguchi, Shuichi Sekine, Kousei Ito, Kiyoko Bando
Troglitazone and pioglitazone were developed as thiazolidinedione-type anti-diabetes drugs, but only troglitazone was withdrawn from the markets due to severe liver injury. As both troglitazone and its sulfate metabolite are strong inhibitors of the bile salt export pump (BSEP), troglitazone-induced bile acid (BA) retention is thought to be one of the underlying mechanisms of liver injury. However, pioglitazone is also a strong BSEP inhibitor, indicating other mechanisms may also be involved in troglitazone-induced BA retention...
May 9, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28482342/pioglitazone-attenuates-injury-induced-neointima-formation-in-mouse-femoral-artery-partially-through-the-activation-of-amp-activated-protein-kinase
#16
Islam Osman, Arwa Fairaq, Lakshman Segar
BACKGROUND/AIMS: Pioglitazone (PIO), an antidiabetic drug, has been shown to attenuate vascular smooth muscle cell (VSMC) proliferation, which is a major event in atherosclerosis and restenosis after angioplasty. Till date, the likely contributory role of AMP-activated protein kinase (AMPK) toward PIO inhibition of VSMC proliferation has not been examined in vivo. This study is aimed at determining whether pharmacological inhibition of AMPK would prevent the inhibitory effect of PIO on neointima formation in a mouse model of arterial injury...
May 9, 2017: Pharmacology
https://www.readbyqxmd.com/read/28471499/efficacy-and-safety-of-single-drug-or-double-drug-antidiabetic-regimens-in-the-treatment-of-type-2-diabetes-mellitus-a-network-meta-analysis
#17
Xi-Ling Yang, Mi-Ma Duo-Ji, Zi-Wen Long
A network meta-analysis was performed in order compare the efficacy and safety of single-drug or double-drug antidiabetic regimens in the treatment of type 2 diabetes mellitus (T2DM). PubMed and Cochrane Library searches were conducted since inception to February 2017. Randomized controlled trials (RCTs) of different antidiabetic regimens in the treatment of T2DM were included in this study. Direct and indirect evidences were combined to calculate the odds ratio (OR) or weighted mean difference (WMD) and its 95% confidence interval (95% CI), and in order to draw the surface under the cumulative ranking curves (SUCRA)...
May 4, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28470881/concentration-dependent-response-to-pioglitazone-in-nonalcoholic-steatohepatitis
#18
M Kawaguchi-Suzuki, F Bril, S Kalavalapalli, K Cusi, R F Frye
BACKGROUND: Pioglitazone is a safe and effective option to manage patients with type 2 diabetes and nonalcoholic steatohepatitis (NASH). However, there is marked variability in treatment response. AIM: To evaluate the relationship between concentrations of pioglitazone and its active metabolites and treatment outcomes in patients with NASH. METHODS: Pioglitazone concentrations were measured in patients with NASH treated with pioglitazone 45 mg/day for 18 months; liver biopsy samples were obtained at baseline and after treatment...
May 3, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28467929/ppar%C3%AE-links-bmp2-and-tgf%C3%AE-1-pathways-in-vascular-smooth-muscle-cells-regulating-cell-proliferation-and-glucose-metabolism
#19
Laurent Calvier, Philippe Chouvarine, Ekaterina Legchenko, Nadine Hoffmann, Jonas Geldner, Paul Borchert, Danny Jonigk, Miklos M Mozes, Georg Hansmann
BMP2 and TGFβ1 are functional antagonists of pathological remodeling in the arteries, heart, and lung; however, the mechanisms in VSMCs, and their disturbance in pulmonary arterial hypertension (PAH), are unclear. We found a pro-proliferative TGFβ1-Stat3-FoxO1 axis in VSMCs, and PPARγ as inhibitory regulator of TGFβ1-Stat3-FoxO1 and TGFβ1-Smad3/4, by physically interacting with Stat3 and Smad3. TGFβ1 induces fibrosis-related genes and miR-130a/301b, suppressing PPARγ. Conversely, PPARγ inhibits TGFβ1-induced mitochondrial activation and VSMC proliferation, and regulates two glucose metabolism-related enzymes, platelet isoform of phosphofructokinase (PFKP, a PPARγ target, via miR-331-5p) and protein phosphatase 1 regulatory subunit 3G (PPP1R3G, a Smad3 target)...
May 2, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28465099/structure-activity-relationships-of-rosiglitazone-for-peroxisome-proliferator-activated-receptor-gamma-transrepression
#20
Yosuke Toyota, Sayaka Nomura, Makoto Makishima, Yuichi Hashimoto, Minoru Ishikawa
Anti-inflammatory effects of peroxisome proliferator-activated receptor gamma (PPRAγ) ligands are thought to be largely due to PPARγ-mediated transrepression. Thus, transrepression-selective PPARγ ligands without agonistic activity or with only partial agonistic activity should exhibit anti-inflammatory properties with reduced side effects. Here, we investigated the structure-activity relationships (SARs) of PPARγ agonist rosiglitazone, focusing on transrepression activity. Alkenic analogs showed slightly more potent transrepression with reduced efficacy of transactivating agonistic activity...
April 20, 2017: Bioorganic & Medicinal Chemistry Letters
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