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Pingping Xia, Yundan Pan, Fan Zhang, Na Wang, E Wang, Qulian Guo, Zhi Ye
BACKGROUND/AIMS: Recent researches highlighted the protective potential of pioglitazone, a PPAR-γ agonist, in the progression of cerebral ischemia-reperfusion injury. However, there has been no study on the application of pioglitazone in treating ischemic stroke through mechanisms involving pyroptosis. METHODS: The cerebral injury was established by middle cerebral artery occlusion (MCAO). in vitro ischemia in primary cultured astrocytes was induced by the oxygen-glucose deprivation (OGD)...
March 13, 2018: Cellular Physiology and Biochemistry
Chunmei Xu, Junyu Zhao, Xiaojun Zhou, Rui Zhang, Tianyue Xie, Zhiwei Zou, Lin Liao, Jianjun Dong
Background: Liver enzyme abnormalities are common in patients with type 2 diabetes. Currently, the inverse relationship between elevated liver enzymes and antidiabetics intake may be explained by rigorous treatment and good control. However, few studies have directly explored the influence of antidiabetics on abnormal liver function, especially the comparison between two insulin sensitizers-thiazolidinediones and metformin. Materials And Methods: Databases, including PubMed, Cochrane, CNKI, Wanfang and VIP were searched...
February 23, 2018: Oncotarget
Stephen Caltabiano, Kelly M Mahar, Karyn Lister, David Tenero, Ramiya Ravindranath, Borut Cizman, Alexander R Cobitz
This study was conducted to evaluate the likelihood of daprodustat to act as a perpetrator in drug-drug interactions (DDI) with the CYP2C8 enzyme and OATP1B1 transporter using the probe substrates pioglitazone and rosuvastatin as potential victims, respectively. Additionally, this study assessed the effect of a weak CYP2C8 inhibitor, trimethoprim, as a perpetrator of a DDI with daprodustat. This was a two-part study: Part A assessed the effect of coadministration of daprodustat on the pharmacokinetics of pioglitazone and rosuvastatin in 20 subjects; Part B assessed the coadministration of trimethoprim on the pharmacokinetics of daprodustat in 20 subjects...
April 2018: Pharmacology Research & Perspectives
Xin Qian, Hui Wang, Gangyi Yang, Zhengnan Gao, Yong Luo, Aimei Dong, Fang Zhang, Mingtong Xu, Shiping Liu, Xin Yang, Yanyan Chen, Guangwei Li
INTRODUCTION: To investigate the effects of pioglitazone (PIO) on insulin resistance and first phase insulin secretion among obese and lean Chinese people with type 2 diabetes mellitus (T2DM). METHODS: Sixty-eight drug-naïve patients with T2DM were treated with PIO for 16 weeks. Before and after the treatment, insulin sensitivity was evaluated by the euglycemic hyperinsulinemic clamp test. Plasma insulin levels at 0, 3, 5, 7, and 10 min during intravenous glucose tolerance test were determined to calculate the first phase insulin secretion and pancreatic β-cell function...
March 13, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Ji-Quan Zhang, Shu-Min Li, Xiao Ma, Gang Zhong, Rui Chen, Xiao-Shuang Li, Gao-Feng Zhu, Bo Zhou, Bing Guo, Hao-Shu Wu, Lei Tang
A series of tetrahydrocarbazole derivatives was designed and synthesized on the basis of the AMP-activated protein kinase activator GY3. All the synthesized compounds were screened in HepG2 cell lines for glucose consumption activity and several of them showed potent glucose decreasing activity. In vivo evaluation of the hypoglycemic and hypolipemic effects indicated that 7a exhibited comparable activity with pioglitazone, but with a weaker body-weight increasing effect. The pharmacokinetic profiles of 7a were also investigated...
February 24, 2018: European Journal of Medicinal Chemistry
Jacki L Coburn, Toby B Cole, Khoi T Dao, Lucio G Costa
Adult neurogenesis is the process by which neural stem cells give rise to new functional neurons in specific regions of the adult brain, a process that occurs throughout life. Significantly, neurodegenerative and psychiatric disorders present suppressed neurogenesis, activated microglia, and neuroinflammation. Traffic-related air pollution has been shown to adversely affect the central nervous system. As the cardinal effects of air pollution exposure are microglial activation, and ensuing oxidative stress and neuroinflammation, we investigated whether acute exposures to diesel exhaust (DE) would inhibit adult neurogenesis in mice...
March 10, 2018: Archives of Toxicology
Petar M Seferović, Mark C Petrie, Gerasimos S Filippatos, Stefan D Anker, Giuseppe Rosano, Johann Bauersachs, Walter J Paulus, Michel Komajda, Francesco Cosentino, Rudolf A de Boer, Dimitrios Farmakis, Wolfram Doehner, Ekaterini Lambrinou, Yuri Lopatin, Massimo F Piepoli, Michael J Theodorakis, Henrik Wiggers, John Lekakis, Alexandre Mebazaa, Mamas A Mamas, Carsten Tschöpe, Arno W Hoes, Jelena P Seferović, Jennifer Logue, Theresa McDonagh, Jillian P Riley, Ivan Milinković, Marija Polovina, Dirk J van Veldhuisen, Mitja Lainscak, Aldo P Maggioni, Frank Ruschitzka, John J V McMurray
The coexistence of type 2 diabetes mellitus (T2DM) and heart failure (HF), either with reduced (HFrEF) or preserved ejection fraction (HFpEF), is frequent (30-40% of patients) and associated with a higher risk of HF hospitalization, all-cause and cardiovascular (CV) mortality. The most important causes of HF in T2DM are coronary artery disease, arterial hypertension and a direct detrimental effect of T2DM on the myocardium. T2DM is often unrecognized in HF patients, and vice versa, which emphasizes the importance of an active search for both disorders in the clinical practice...
March 8, 2018: European Journal of Heart Failure
Anne Pernille Ofstad, Dan Atar, Lars Gullestad, Gisle Langslet, Odd Erik Johansen
Diabetes and heart failure (HF) are both global epidemics with tremendous costs on society with increased rates of HF hospitalizations and worsened prognosis when co-existing, making it a significant "deadly duo." The evidence for pharmacological treatment of HF in patients with type 2 diabetes mellitus (T2DM) stems typically from either subgroup analyses of patients that were recruited to randomized controlled trials of HF interventions, usually in patients with reduced ejection fraction (EF), or from subgroup analyses of HF patients recruited to cardiovascular (CV) outcome trials (CVOT) of glucose lowering agents involving patients with T2DM...
March 8, 2018: Heart Failure Reviews
Hiroshi Tobita, Shuichi Sato, Tomotaka Yazaki, Tsuyoshi Mishiro, Norihisa Ishimura, Shunnji Ishihara, Yoshikazu Kinoshita
Pioglitazone (PIO) has been reported to be effective for nonalcoholic fatty liver disease (NAFLD) and alogliptin (ALO) may have efficacy against NAFLD progression in patients with type 2 diabetes mellitus (T2DM). The present study examined the effectiveness of ALO in a rodent model of NAFLD and diabetes mellitus. KK‑Ay mice were used to produce an NAFLD model via administration of a choline‑deficient (CD) diet. To examine the effects of alogliptin, KK‑Ay mice were provided with a CD diet with 0.03% ALO and/or 0...
March 1, 2018: Molecular Medicine Reports
Amir M Abdelhamid, Rania Ramadan Abdelaziz, Hatem A Salem
Type I diabetes (TID) is generally assumed to be caused by an immune associated, if not directly immune-mediated, destruction of pancreatic β-cells. In patients with long-term diabetes, the pancreas lacks insulin-producing cells and the residual β-cells are unable to regenerate. Patients with TID are subjected to a lifelong insulin therapy which shows risks of hypoglycemia, suboptimal control and ketosis. In this study, we investigated the potential role of Vildagliptin (Vilda) alone or in combination with Pioglitazone (Pio), as treatment regimens for TID using Streptozotocin (STZ) induced TID model in rats...
March 6, 2018: Canadian Journal of Physiology and Pharmacology
Kamlesh Khunti, Sudesna Chatterjee, Hertzel C Gerstein, Sophia Zoungas, Melanie J Davies
Sulphonylureas have been commercially available since the 1950s, but their use continues to be associated with controversy. Although adverse cardiovascular outcomes in some observational studies have raised concerns about sulphonylureas, findings from relatively recent, robust, and high-quality systematic reviews have indicated no increased risk of all-cause mortality associated with sulphonylureas compared with other active treatments. Results from large, multicentre, randomised controlled trials such as the UK Prospective Diabetes Study and ADVANCE have confirmed the microvascular benefits of sulphonylureas, a reduction in the incidence or worsening of nephropathy and retinopathy, and no increase in all-cause mortality, although whether these benefits were due to sulphonylurea therapy and not an overall glucose-lowering effect could not be confirmed...
February 28, 2018: Lancet Diabetes & Endocrinology
Brian Mac Grory, Shadi Yaghi
In this article, we discuss major advances in the treatment and prevention of ischemic stroke that have taken placed in the past 3 years. The most important advance in acute stroke treatment is the validation and widespread adoption of intra-arterial therapies for the treatment of acute ischemic stroke. Five clinical trials spanning multiple continents were published in early 2015 that proved that intra-arterial treatment - both with and without tPA - is beneficial in improving functional recovery after stroke...
March 1, 2018: Rhode Island Medical Journal
Atsushi Tanaka, Sho Komukai, Yoshisato Shibata, Hiroyoshi Yokoi, Yoshihiro Iwasaki, Tomohiro Kawasaki, Kenji Horiuchi, Koichi Nakao, Takafumi Ueno, Hitoshi Nakashima, Masahiro Tamashiro, Yutaka Hikichi, Mitsuhiro Shimomura, Motoko Tago, Shigeru Toyoda, Teruo Inoue, Atsushi Kawaguchi, Koichi Node
Pioglitazone has superior antiatherosclerotic effects compared with other classes of antidiabetic agents, and there is substantial evidence that pioglitazone improves cardiovascular (CV) outcomes. However, there is also a potential risk of worsening heart failure (HF). Therefore, it is clinically important to determine whether pioglitazone is safe in patients with type 2 diabetes mellitus (T2DM) who require treatment for secondary prevention of CV disease, since they have an intrinsically higher risk of HF...
February 27, 2018: Heart and Vessels
Fu-Sun Lo, Reha S Erzurumlu
Background: Met receptor tyrosine kinase regulates neurogenesis, differentiation, migration, connectivity, and synaptic plasticity. The human Met gene has been identified as a prominent risk factor for autism spectrum disorder (ASD). Met gene-altered mice serve as useful models for mechanistic studies of ASD. Inactivation of Met in excitatory cortical neurons in mice ( Emx1 cre /Met flox mice) yields a phenotype in which significantly decreased GABAA receptor-mediated inhibition shifts the excitation/inhibition (E/I) balance toward excitation in the somatosensory cortex...
2018: Molecular Autism
Shao-Ling Yang, Ji-Jiao Wang, Ming Chen, Lu Xu, Nan Li, Yi-Li Luo, Le Bu, Man-Na Zhang, Hong Li, Ben-Li Su
Aims: Whether pioglitazone (PIO), a peroxisome proliferator-activated receptor-gamma agonist, increases the risk of developing bladder cancer has been debated for several years. The aim of this study was to investigate the in vitro effects of PIO on normal urothelial transitional epithelium (NUTE) cells and bladder cancer (J82) cells to further evaluate the risk. Methods: NUTE cells were obtained from Sprague-Dawley rats. NUTE and J82 cells were treated with different concentrations of PIO for various time periods...
2018: International Journal of Medical Sciences
John Lally, Aonghus O' Loughlin, Brendon Stubbs, Allys Guerandel, Donal O'Shea, Fiona Gaughran
The increased prevalence of Type 2 diabetes mellitus (T2DM) in severe mental illness (SMI) contributes to increased cardiovascular morbidity and reduced life expectancy for people with SMI. Areas covered: In the present clinical review, we summarize the efficacy, safety and tolerability of selected diabetic pharmacotherapy options in SMI and discuss the quality and strength of evidence. Expert commentary: General principles for treating T2DM in SMI involve identifying treatments which promote weight loss and which have low or no risk of hypoglycemia...
February 26, 2018: Expert Review of Clinical Pharmacology
Huilin Tang, Weilong Shi, Shuangshuang Fu, Tiansheng Wang, Suodi Zhai, Yiqing Song, Jiali Han
Current evidence about the association between pioglitazone and bladder cancer risk remains conflict. We aimed to assess the risk of bladder cancer associated with the use of pioglitazone and identify modifiers that affect the results. We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials from inception to 25 August 2016 for randomized controlled trials (RCTs) and observational studies that evaluated the association between pioglitazone and bladder cancer risk. Conventional and cumulative meta-analyses were used to calculate the odds ratio (OR) with 95% confidence interval (CI)...
February 24, 2018: Cancer Medicine
Negin Jamali Emam Gheise, Ahmad Riasi, Pietro Celi, Ahmad Zare Shahneh
No abstract text is available yet for this article.
February 2018: Journal of Dairy Research
Isabel Quesada, Jimena Cejas, Rodrigo García, Beatriz Cannizzo, Analía Redondo, Claudia Castro
AIM: Perivascular adipose tissue (PVAT) is in intimate contact with the vessel wall and extravascular PVAT-derived inflammatory mediators may adversely influence atherosclerotic plaque formation and stability through outside-to-inside signalling. We sought to investigate the role of PVAT on the atheroma development in an experimental animal model of Metabolic Syndrome (MS) associated with oxidative stress and low-grade inflammatory state. We also studied the effect of Pioglitazone an insulin sensitizer, on the aortic wall and its surrounding PVAT, considering a bi-directional communication between both layers...
February 21, 2018: Cardiovascular Therapeutics
Zhao-Jun Wang, Hai-Bin Zhang, Cheng Chen, Hao Huang, Jian-Xia Liang
Accumulation of advanced glycation end products (AGEs) in articular cartilage is thought to represent a major risk factor for osteoarthritis development. In this study we aimed to probe the role of AGEs in human chondrocytes and to determine the impact of the peroxisome proliferator-activated receptor-γ (PPARG) on AGEs-induced cell autophagy. Cell viability was measured after human chondrocytes were treated with different concentrations of AGEs with or without the PPARG inhibitor, T0070907, or agonist, pioglitazone...
February 17, 2018: Cell Biology International
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