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Sample records for pioglitazone treatment increases

  1. Pioglitazone treatment increases spontaneous growth hormone (GH) secretion and stimulated GH levels in polycystic ovary syndrome

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    Glintborg, Dorte; Støving, René Klinkby; Hagen, Claus

    2005-01-01

    and improved insulin sensitivity during pioglitazone treatment may affect GH secretion. OBJECTIVE: The objective of the study was to investigate the effect of pioglitazone on GH levels in PCOS. DESIGN: Thirty insulin-resistant PCOS patients were randomized to either 16 wk pioglitazone (30 mg/d) or placebo...... treatment. Before and after intervention, levels of fasting insulin, GH, total IGF-I, free IGF-I, IGF binding protein-1, IGF-II, free fatty acids, testosterone, and SHBG were measured. Patients underwent whole-body dual x-ray absorptiometry scans, pyridostigmine-GHRH tests, and 24-h 20-min integrated blood...... sampling for measurement of GH. RESULTS: Peak GH and area under the curve for GH in pyridostigmine-GHRH tests and 24-h mean GH concentrations and pulsatile GH secretion significantly increased after pioglitazone treatment. No significant changes were observed in GH pulse frequency, pulse duration...

  2. Reduced serum dipeptidyl peptidase-IV after metformin and pioglitazone treatments.

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    Lenhard, James M; Croom, Dallas K; Minnick, Dana T

    2004-11-05

    Dipeptidyl peptidase-IV (DPP-IV) regulates metabolism by degrading incretins involved in nutritional regulation. Metformin and pioglitazone improve insulin sensitivity whereas glyburide promotes insulin secretion. Zucker diabetic rats were treated with these antidiabetic agents for 2 weeks and DPP-IV activity and expression were determined. Serum DPP-IV activity increased whereas tissue activity decreased as the rats aged. Treatment of rats with metformin, pioglitazone, and glyburide did not alter DPP-IV mRNA expression in liver or kidney. Metformin and pioglitazone significantly (PMetformin, pioglitazone, and glyburide had no effect on serum DPP-IV activity in vitro, indicating these are not competitive DPP-IV inhibitors. We propose the in vivo inhibitory effects observed with metformin and pioglitazone on serum DPP-IV activity results from reduced DPP-IV secretion.

  3. Treatment with pioglitazone is associated with decreased preprandial ghrelin levels: a randomized clinical trial.

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    Taslimi, Shervin; Esteghamati, Alireza; Rashidi, Armin; Tavakkoli, Hosein Moin; Nakhjavani, Manouchehr; Kebriaee-Zadeh, Abbas

    2013-02-01

    The effects of metformin and pioglitazone on ghrelin, a physiologic regulator of appetite and food intake, have not been clearly established. In a randomized clinical trial, we randomly assigned 60 type 2 diabetic patients to either metformin (Group A; n=30) or pioglitazone (Group B; n=30) treatment groups. The groups were similar in their baseline characteristics. A standard fasting 75 g oral glucose tolerance test was performed at time zero before starting metformin or pioglitazone, and 3 months later. After 3 months of treatment, pioglitazone, but not metformin, was significantly associated with weight gain. Both groups experienced a significant reduction in fasting plasma glucose (ppioglitazone group had a significant reduction in preprandial ghrelin levels after treatment (ppioglitazone on ghrelin was independent of changes in body weight, body mass index, glucose control, insulin resistance, and plasma insulin. In conclusion, treatment with pioglitazone is associated with a decrease in preprandial ghrelin levels and therefore, the weight gain and increased food intake related to pioglitazone use cannot be explained by its effects on ghrelin. The effect of pioglitazone on ghrelin is independent of changes in body weight, body mass index, plasma insulin, insulin resistance, or glucose control.

  4. Effects of red mold dioscorea with pioglitazone, a potentially functional food, in the treatment of diabetes

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    Chien-Li Chen

    2015-12-01

    Full Text Available The prevalence of type 2 diabetes mellitus is increasing rapidly, and its treatment with pioglitazone is likely to induce rhabdomyolysis. We aimed to determine the effect of cotreatment with pioglitazone and red mold dioscorea (RMD produced by Monascus purpureus NTU 568 on pancreas function in streptozotocin (STZ-induced diabetic rats. In diabetic rats fed RMD, RMD with pioglitazone, and pioglitazone alone, insulin concentrations increased significantly by 18.6–40.4%, 64.0–100.0%, and 52.8%, respectively, compared with that in the diabetic group (p < 0.05. Oral glucose tolerance was impaired in the STZ-induced diabetic group within 4 weeks, however, oral glucose tolerance in rats treated with RMD or RMD with pioglitazone improved after 4 weeks, 6 weeks, and 8 weeks. Findings from this study might lend support to the use of RMD as a novel functional food for the prevention of diabetes.

  5. Plasma osteoprotegerin is associated with testosterone levels but unaffected by pioglitazone treatment in patients with polycystic ovary syndrome

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    Glintborg, D; Hermann, Pernille; Rasmussen, Lars Melholt;

    2013-01-01

    Objective Increased osteoprotegerin (OPG) levels are associated with increased cardiovascular risk and decreased bone resorption. Pioglitazone treatment reduces the inflammatory state but may decrease bone mineral density. OPG levels during pioglitazone treatment have not previously been evaluated...... in polycystic ovary syndrome (PCOS). Research design and methods Plasma OPG levels were measured in 30 PCOS patients before and after randomized treatment with 30 mg pioglitazone/placebo for 16 weeks. Fourteen age and BMI matched healthy women were included as controls. Clinical and hormonal evaluations...

  6. Pioglitazone treatment reduces adipose tissue inflammation through reduction of mast cell and macrophage number and by improving vascularity.

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    Michael Spencer

    Full Text Available Adipose tissue in insulin resistant subjects contains inflammatory cells and extracellular matrix components. This study examined adipose pathology of insulin resistant subjects who were treated with pioglitazone or fish oil.Adipose biopsies were examined from nine insulin resistant subjects before/after treatment with pioglitazone 45 mg/day for 12 weeks and also from 19 subjects who were treated with fish oil (1,860 mg EPA, 1,500 mg DHA daily. These studies were performed in a clinical research center setting.Pioglitazone treatment increased the cross-sectional area of adipocytes by 18% (p = 0.01, and also increased capillary density without affecting larger vessels. Pioglitazone treatment decreased total adipose macrophage number by 26%, with a 56% decrease in M1 macrophages and an increase in M2 macrophages. Mast cells were more abundant in obese versus lean subjects, and were decreased from 24 to 13 cells/mm(2 (p = 0.02 in patients treated with pioglitazone, but not in subjects treated with FO. Although there were no changes in total collagen protein, pioglitazone increased the amount of elastin protein in adipose by 6-fold.The PPARγ agonist pioglitazone increased adipocyte size yet improved other features of adipose, increasing capillary number and reducing mast cells and inflammatory macrophages. The increase in elastin may better permit adipocyte expansion without triggering cell necrosis and an inflammatory reaction.

  7. Effect of pioglitazone treatment in a patient with secondary multiple sclerosis

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    Pershadsingh Harrihar A

    2004-04-01

    Full Text Available Abstract Background Ligands of the peroxisome proliferator-activated receptor-gamma (PPARγ induce apoptosis in activated T-lymphocytes and exert anti-inflammatory effects in glial cells. Preclinical studies have shown that the thiazolidinedione pioglitazone, an FDA-approved PPARγ agonist used to treat type 2 diabetes, delays the onset and reduces the severity of clinical symptoms in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS. We therefore tested the safety and therapeutic potential of oral pioglitazone in a patient with secondary MS. Case presentation The rationale and risks of taking pioglitazone were carefully explained to the patient, consent was obtained, and treatment was initiated at 15 mg per day p.o. and then increased by 15 mg biweekly to 45 mg per day p.o. for the duration of the treatment. Safety was assessed by measurements of metabolic profiles, blood pressure, and edema; effects on clinical symptoms were assessed by measurement of cognition, motor function and strength, and MRI. Within 4 weeks the patient exhibited increased appetite, cognition and attention span. After 12 months treatment, body weight increased from 27.3 to 35.9 kg (32% and maintained throughout the duration of the study. Upper extremity strength and coordination improved, and increased fine coordination was noted unilaterally after 8 months and bilaterally after 15 months. After 8 months therapy, the patient demonstrated improvement in orientation, short-term memory, and attention span. MRIs carried out after 10 and 18 months of treatment showed no perceptible change in overall brain atrophy, extent of demyelination, or in Gd-enhancement. After 3.0 years on pioglitazone, the patient continues to be clinically stable, with no adverse events. Conclusions In a patient with secondary progressive MS, daily treatment with 45 mg p.o. pioglitazone for 3 years induced apparent clinical improvement without adverse events

  8. Effect of pioglitazone treatment on behavioral symptoms in autistic children

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    Edelson Stephen M

    2007-01-01

    Full Text Available Abstract Introduction Autism is complex neuro-developmental disorder which has a symptomatic diagnosis in patients characterized by disorders in language/communication, behavior, and social interactions. The exact causes for autism are largely unknown, but is has been speculated that immune and inflammatory responses, particularly those of Th2 type, may be involved. Thiazolidinediones (TZDs are agonists of the peroxisome proliferator activated receptor gamma (PPARγ, a nuclear hormone receptor which modulates insulin sensitivity, and have been shown to induce apoptosis in activated T-lymphocytes and exert anti-inflammatory effects in glial cells. The TZD pioglitazone (Actos is an FDA-approved PPARγ agonist used to treat type 2 diabetes, with a good safety profile, currently being tested in clinical trials of other neurological diseases including AD and MS. We therefore tested the safety and therapeutic potential of oral pioglitazone in a small cohort of children with diagnosed autism. Case description The rationale and risks of taking pioglitazone were explained to the parents, consent was obtained, and treatment was initiated at either 30 or 60 mg per day p.o. A total of 25 children (average age 7.9 ± 0.7 year old were enrolled. Safety was assessed by measurements of metabolic profiles and blood pressure; effects on behavioral symptoms were assessed by the Aberrant Behavior Checklist (ABC, which measures hyperactivity, inappropriate speech, irritability, lethargy, and stereotypy, done at baseline and after 3–4 months of treatment. Discussion and evaluation In a small cohort of autistic children, daily treatment with 30 or 60 mg p.o. pioglitazone for 3–4 months induced apparent clinical improvement without adverse events. There were no adverse effects noted and behavioral measurements revealed a significant decrease in 4 out of 5 subcategories (irritability, lethargy, stereotypy, and hyperactivity. Improved behaviors were inversely

  9. Effect of Chronic Pioglitazone Treatment on Hepatic Gene Expression Profile in Obese C57BL/6J Mice.

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    Jia, Chunming; Huan, Yi; Liu, Shuainan; Hou, Shaocong; Sun, Sujuan; Li, Caina; Liu, Quan; Jiang, Qian; Wang, Yue; Shen, Zhufang

    2015-05-29

    Pioglitazone, a selective ligand of peroxisome proliferator-activated receptor gamma (PPARγ), is an insulin sensitizer drug that is being used in a number of insulin-resistant conditions, including non-alcoholic fatty liver disease (NAFLD). However, there is a discrepancy between preclinical and clinical data in the literature and the benefits of pioglitazone treatment as well as the precise mechanism of action remain unclear. In the present study, we determined the effect of chronic pioglitazone treatment on hepatic gene expression profile in diet-induced obesity (DIO) C57BL/6J mice in order to understand the mechanisms of NAFLD induced by PPARγ agonists. DIO mice were treated with pioglitazone (25 mg/kg/day) for 38 days, the gene expression profile in liver was evaluated using Affymetrix Mouse GeneChip 1.0 ST array. Pioglitazone treatment resulted in exacerbated hepatic steatosis and increased hepatic triglyceride and free fatty acids concentrations, though significantly increased the glucose infusion rate in hyperinsulinemic-euglycemic clamp test. The differentially expressed genes in liver of pioglitazone treated vs. untreated mice include 260 upregulated and 86 downregulated genes. Gene Ontology based enrichment analysis suggests that inflammation response is transcriptionally downregulated, while lipid metabolism is transcriptionally upregulated. This may underlie the observed aggravating liver steatosis and ameliorated systemic insulin resistance in DIO mice.

  10. Pioglitazone increases the glycolytic efficiency of human Sertoli cells with possible implications for spermatogenesis.

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    Meneses, M J; Bernardino, R L; Sá, R; Silva, J; Barros, A; Sousa, M; Silva, B M; Oliveira, P F; Alves, M G

    2016-10-01

    Pioglitazone is a synthetic agonist for the nuclear receptor peroxisome proliferator-activated receptor γ used to treat type 2 diabetes mellitus. Recently we reported that antidiabetic drugs regulate the nutritional support of spermatogenesis by Sertoli cells. Herein, we investigate the effects of pioglitazone on human Sertoli cells metabolism. Human Sertoli cells were cultured in the presence of pioglitazone (1, 10, 100μM). Protein levels of phosphofructokinase 1, lactate dehydrogenase, hexokinase, glucose transporters (GLUT1, GLUT2, GLUT3), monocarboxylate transporter 4 and oxidative phosphorylation complexes were determined by Western blot. Lactate dehydrogenase and alanine aminotransferase activity were assessed and metabolite production and consumption determined by proton nuclear magnetic resonance. Mitochondrial membrane potential was also determined. Glucose consumption more than doubled in human Sertoli cells stimulated with pioglitazone 100μM. Mitochondrial complex II protein levels increased 50% with exposure to pioglitazone (100μM) in human Sertoli cells, though mitochondrial membrane potential was decreased by 32%. The pharmacological concentration of pioglitazone (10μM) almost doubled lactate production and established crucial correlations among key intervenient of glycolysis. Moreover, in the same concentration, alanine aminotransferase decreased more than 80%. Our results suggest that pioglitazone (10μM) increases the efficiency of the glycolytic flux and lactate production by human Sertoli cells, which is essential to sustain and preserve the spermatogenic event. Thus, pioglitazone may improve male fertility and thus, be considered a suitable antidiabetic drug for men in reproductive age.

  11. Use of pioglitazone in the treatment of diabetes: effect on cardiovascular risk.

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    Zou, Cong; Hu, Honglin

    2013-01-01

    Pioglitazone and other thiazolidinediones (TZDs) initially showed great promise as unique receptor-mediated oral therapy for type 2 diabetes, but a host of serious side effects, primarily cardiovascular, have limited their utility. It is crucial at this point to perform a risk- benefit analysis to determine what role pioglitazone should play in our current treatment of type 2 diabetes and where the future of this class of drugs is headed. This review provides a comprehensive overview of the present literature. Clinical data currently available indicate that pioglitazone is an effective and generally well-tolerated treatment option for use in patients with type 2 diabetes. Pioglitazone can still reduce adverse cardiovascular risk.

  12. Gender differences in non-glycemic responses to improved insulin sensitivity by pioglitazone treatment in patients with type 2 diabetes.

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    Arnetz, Lisa; Dorkhan, Mozhgan; Alvarsson, Michael; Brismar, Kerstin; Ekberg, Neda Rajamand

    2014-04-01

    Excess cortisol and GH induce insulin resistance, a central feature of type 2 diabetes (T2D). To study whether the insulin sensitizer pioglitazone affects basal cortisol levels and the GH-IGF-I axis in patients with T2D. Forty-eight patients with T2D (men/women = 28:20, age 61 ± 1 years, BMI 31 ± 0.6 kg/m(2)) were treated for 26 weeks with pioglitazone 30-45 mg daily in addition to their preexisting therapy. Insulin, proinsulin, HbA(1c), IGF-I, IGFBP-1, and basal cortisol were analyzed before and after treatment. Pioglitazone decreased proinsulin/insulin ratio and HbA(1c) decreased (HbA(1c) from 7.8 ± 0.2 to 6.6 ± 0.2% in men and from 7.6 ± 0.2 to 6.1 ± 0.2% in women, p pioglitazone increased IGF-I regardless of gender and in women also increased basal cortisol. Increased IGF-I may contribute to improved insulin sensitivity after treatment. There seems to be gender differences in treatment responses to pioglitazone on lipid metabolism and basal cortisol, perhaps correcting different mechanisms of insulin resistance between genders.

  13. Effect of pioglitazone on outcome following curative treatment for hepatocellular carcinoma in patients with hepatitis C virus infection: A prospective study.

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    Sumie, Shuji; Kawaguchi, Takumi; Kawaguchi, Atsushi; Kuromatsu, Ryoko; Nakano, Masahito; Satani, Manabu; Yamada, Shingo; Okamura, Shusuke; Yonezawa, Yuko; Kakuma, Tatsuyuki; Torimura, Takuji; Sata, Michio

    2015-01-01

    Pioglitazone is an insulin sensitizer used for the treatment of diabetes mellitus (DM). DM with insulin resistance is a risk factor for hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) infection. We aimed to investigate the effects of pioglitazone on HCC recurrence following treatment in HCV-infected patients. Between 2009 and 2011, 85 HCV-infected HCC patients who underwent curative treatment were enrolled in this prospective study. Among 45 patients with type 2 DM, 27 were administered pioglitazone (pioglitazone group) following treatment. The remaining 58 patients were assigned to the control group. The primary outcome was recurrence-free survival. Changes in insulin resistance and serum adiponectin levels resulting from pioglitazone treatment were also assessed. In the whole analysis (n=85), no significant difference in recurrence-free survival was observed between the pioglitazone and control groups. However, in a spline model analysis of DM patients, a decreased risk of HCC recurrence was associated with increased body weight in patients with a body mass index (BMI) ≥23; this association became significant at BMI ≥24 (hazard ratio=0.17; 95% confidence interval: 0.03-0.95). In addition, significantly decreased homeostasis model assessment for insulin resistance values (P=0.002) and significantly increased serum high-molecular-weight adiponectin levels (Ppioglitazone treatment. Although pioglitazone did not suppress HCC recurrence in the whole analysis, it inhibited HCC recurrence in overweight HCV-infected diabetic patients. Moreover, pioglitazone improved insulin resistance and adipocytokine levels. Thus, pioglitazone may suppress HCC recurrence, which is associated with glucose and fat metabolism disorders.

  14. Pioglitazone and alogliptin combination therapy in type 2 diabetes: a pathophysiologically sound treatment.

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    Triplitt, Curtis; Cersosimo, Eugenio; DeFronzo, Ralph A

    2010-09-07

    Insulin resistance and islet (beta and alpha) cell dysfunction are major pathophysiologic abnormalities in type 2 diabetes mellitus (T2DM). Pioglitazone is a potent insulin sensitizer, improves pancreatic beta cell function and has been shown in several outcome trials to lower the risk of atherosclerotic and cardiovascular events. Glucagon-like peptide-1 deficiency/resistance contributes to islet cell dysfunction by impairing insulin secretion and increasing glucagon secretion. Dipeptidyl peptidase-4 (DPP-4) inhibitors improve pancreatic islet function by augmenting glucose-dependent insulin secretion and decreasing elevated plasma glucagon levels. Alogliptin is a new DPP-4 inhibitor that reduces glycosylated hemoglobin (HbA(1c)), is weight neutral, has an excellent safety profile, and can be used in combination with oral agents and insulin. Alogliptin has a low risk of hypoglycemia, and serious adverse events are uncommon. An alogliptin-pioglitazone combination is advantageous because it addresses both insulin resistance and islet dysfunction in T2DM. HbA(1c) reductions are significantly greater than with either monotherapy. This once-daily oral combination medication does not increase the risk of hypoglycemia, and tolerability and discontinuation rates do not differ significantly from either monotherapy. Importantly, measures of beta cell function and health are improved beyond that observed with either monotherapy, potentially improving durability of HbA(1c) reduction. The alogliptin-pioglitazone combination represents a pathophysiologically sound treatment of T2DM.

  15. Plasma monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha are increased in patients with polycystic ovary syndrome (PCOS) and associated with adiposity, but unaffected by pioglitazone treatment

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    Glintborg, Dorte; Andersen, Marianne; Richelsen, Bjørn;

    2009-01-01

    OBJECTIVE: Hirsutism is most often caused by polycystic ovary syndrome (PCOS). PCOS patients are characterized by insulin resistance, abdominal obesity and low-grade inflammation. Insulin sensitizing treatment reduces the inflammatory state, but the effect on serum levels of migration inhibitor...... of adiposity in PCOS patients, but were unchanged during insulin sensitizing treatment with pioglitazone. Our data suggests a fat mass independent association between testosterone and MIF levels in PCOS and the effect of anti-androgen treatment on chemokine levels needs to be examined....

  16. Pioglitazone and cancer: angel or demon?

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    Kostapanos, Michael S; Elisaf, Moses S; Mikhailidis, Dimitri P

    2013-01-01

    After the withdrawal of troglitazone and rosiglitazone, pioglitazone remains the sole thiazolidinedione (TZD) still available. Pioglitazone is efficacious in improving glycemic control and reduce the risk of cardiovascular events. Although generally well-tolerated, pioglitazone was withdrawn by some national medicines agencies (e.g. in France and Germany) due to reports of increased incidence of bladder cancer. In this article, we review the literature on the association between pioglitazone and cancer in several sites, including the bladder. Pioglitazone, like other TZDs, increased differentiation, inhibited growth and proliferation, while provoked apoptosis in various cancer cells, including bladder cancer, in vitro and in vivo. However, a rat-specific carcinogenic effect of pioglitazone on the bladder was noted in vivo. Clinical data for the risk of various cancer sites mostly come from observational studies and are subject to bias. An increased risk for bladder cancer by pioglitazone was suggested by retrospective analyses. This risk was associated with the time of exposure and the age, by identifying 24 months and 65 years, respectively, as time 'thresholds' above which this risk becomes relevant. In contrast, no increased risk for bladder cancer was associated with pioglitazone in randomized clinical trials. Pioglitazone was associated with increased incidence of melanoma and non-Hodgkin lymphoma and decreased risk of renal cancer in one cohort study. These findings need to be re-evaluated on a prospective basis. There is no convincing evidence that pioglitazone increases or decreases the risk of cancer in other sites. In contrast, it was suggested that this drug may be useful either in the treatment of cancer complications or as an adjunct to chemotherapeutic agents. Considering the clinical benefit from the use of pioglitazone it is reasonable to wait until data from ongoing clinical trials are available before reaching definitive conclusions. Nevertheless

  17. Influence of drug transporters and stereoselectivity on the brain penetration of pioglitazone as a potential medicine against Alzheimer's disease.

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    Chang, Kai Lun; Pee, Hai Ning; Yang, Shili; Ho, Paul C

    2015-03-11

    Pioglitazone is currently undergoing clinical trials for treatment of Alzheimer's disease (AD). However, poor brain penetration remains an obstacle to development of the drug for such intended clinical uses. In this study, we demonstrate that the inhibition of P-glycoprotein (P-gp) significantly increases brain penetration of pioglitazone, whereas inhibition of breast cancer resistance protein (BCRP) has little effect. We also investigate the stereoselectivity of pioglitazone uptake in the brain. When mice were dosed with racemic pioglitazone, the concentration of (+)-pioglitazone was 46.6% higher than that of (-)-pioglitazone in brain tissue and 67.7% lower than that of (-)-pioglitazone in plasma. Dosing mice with pure (+)-pioglitazone led to a 76% increase in brain exposure levels compared to those from an equivalent dose of racemic pioglitazone. Pure (+)-pioglitazone was also shown to have comparable amyloid-lowering capabilities to the racemic pioglitazone in an in vitro AD model. These results suggest that P-gp may act as a stereoselective barrier to prevent pioglitazone entry into the brain. Dosing with (+)-pioglitazone instead of the racemic mixture may result in higher levels of brain exposure to pioglitazone, thus potentially improving the development of pioglitazone treatment of AD.

  18. Pioglitazone-induced increase in the stearoyl-CoA desaturation index and fat accumulation in rat muscles are not related to lipoprotein lipase activity.

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    Ochiai, Masaru; Matsuo, Tatsuhiro

    2013-01-01

    Muscular insulin resistance is a characteristic of obesity and type 2 diabetes, but little is known about fatty acid (FA) metabolism in insulin-resistant skeletal muscle. In this study, we investigated the effects of the repeated administration of the PPAR-γ agonist pioglitazone on fat accumulation, FA composition, and stearoyl-CoA desaturase (SCD) index in rat tissues. Seventeen 4-week-old male Wistar rats were divided into control (C, n = 9) and pioglitazone treatment (P, n = 8) groups, and all the rats were fed a high-fat and high-sucrose diet for 8 weeks. Vehicle or pioglitazone (3 mg/kg) was orally administered daily to rats in the C group and P group, respectively. In the eighth week of the test period, an oral glucose tolerance test (OGTT) was performed after 12 h fasting. At the end of the test period, serum, liver, perirenal adipose tissue, and skeletal muscles were removed after 12 h fasting. The fasting serum and plasma glucose concentrations and OGTT glucose and insulin levels were significantly lower, while the serum adiponectin concentration was significantly higher in the P group than in the C group. Pioglitazone administration increased fat accumulation in the various muscle types examined, perirenal adipose tissue, and brown adipose tissue (BAT), but decreased fat accumulation in the liver. Pioglitazone administration increased the SCD indices for the muscles, perirenal adipose tissue, and liver, but not those of BAT. The lipoprotein lipase (LPL) activity of the BAT and perirenal adipose tissue, but not the muscles, was higher in the P group than in the C group. These results indicate that pioglitazone administration improved glucose tolerance and increased fat accumulation and SCD indices in the muscles and adipose tissues of rats. The increased fat accumulation was closely correlated with LPL activity in both adipose tissues, but not in the muscles.

  19. Pioglitazone prescription increases risk of bladder cancer in patients with type 2 diabetes: an updated meta-analysis.

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    He, Shiyao; Tang, Yu-hong; Zhao, Guobin; Yang, Xiaolong; Wang, Dehou; Zhang, Ye

    2014-03-01

    Pioglitazone is widely used for glycemic control in patients with type 2 diabetes mellitus, but evidence regarding the association between pioglitazone and bladder cancer risk is confusing. A systematic search of databases was carried out, and other relevant papers were also identified. Then, the analyses were conducted according to the PRISMA and MOOSE guidelines. After quality assessment, nine datasets from 10 available studies were included on the basis of inclusion criteria. The incidence of bladder cancer among pioglitazone ever users and never users, pooled from four cohort and one randomized studies, were 84.51 and 66.68 per 100,000 person-years, respectively. Nine studies representing 2,596,856 diabetic patients were recognized as eligible for overall study; the result suggested an increased risk of bladder cancer in patients exposed to pioglitazone. A persistent significance was detected after being adjusted by age, gender, and use of other diabetes medications. Subgroup analyses indicated that the significantly increased incidence of bladder cancer was found in men, but not in women. Additionally, the analyses addressing increasing exposure to pioglitazone observed a dose-response relation between exclusive ever use of pioglitazone and bladder cancer in terms of cumulative duration of use and cumulative dosage. With some limitations, our results suggest an increased risk of bladder cancer in diabetic patients using pioglitazone, especially for men with long-term and high-dose exposure. Additional studies are needed to provide more precise evidences to support our results.

  20. Adiponectin gene polymorphism rs2241766 T/G is associated with response to pioglitazone treatment in type 2 diabetic patients from southern China.

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    Hong Yang

    Full Text Available INTRODUCTION: Insulin sensitizing drugs such as pioglitazone are not uniformly treatment effective among individual type 2 diabetic patients. Here, the relationship of pioglitazone efficacy to single nucleotide polymorphisms (SNP of the adiponectin gene, a critical gene directly regulated by the drug, was examined in a cohort of Chinese Han type 2 diabetic patients. METHODS: Eighty type 2 diabetic patients were treated with pioglitazone (15 mg/day for 12 weeks without interruption of their current therapeutic regimen. Fasting plasma glucose, fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR, and glycated hemoglobin (HbA1c% were collected both prior to and following pioglitazone treatment. Response to pioglitazone was defined as a decrease of at least 15% in HbA1c% levels. Three regions of the adiponectin gene containing SNPs (promoter, intron 2 and exon 2, and exon 3 were amplified and sequenced to determine genotype. RESULTS: Serum adiponectin levels were significantly increased (p<0.001 whereas fasting plasma glucose, fasting insulin, HOMA-IR, and HbA1c% values were significantly decreased relative to baseline measurements (p<0.001. Response of patients with TG and TT genotypes at rs2241766 (exon2; 52.9% vs. 12.7%, respectively p = 0.001 was statistically significant relative to all other patients. Amongst rs2241766 TG and TT patients, the mean decrease in HbA1c% levels was greater where the genotype was TG (1.15±0.80 vs. 0.52±0.64, p = 0.001. CONCLUSIONS: The adiponectin gene polymorphism rs2241766 T/G is associated with pioglitazone efficacy in type 2 diabetic patients, and status of the polymorphism may be an important clinical factor to consider prior to pioglitazone treatment.

  1. The Effects of Sub-Chronic Treatment with Pioglitazone on the Septic Mice Mortality in the Model of Cecal Ligation and Puncture: Involvement of Nitric Oxide Pathway

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    Hamed Shafaroodi

    2015-10-01

    Full Text Available Sepsis is a systemic inflammatory response syndrome caused by an infection and remains as a major challenge in health care. Many studies have reported that pioglitazone may display anti-inflammatory effects. This study was designed to evaluate the effect of subchronic treatment with pioglitazone on high-grade septic mice survival and nitrergic system involvement. Diffused sepsis was induced by cecal ligation and puncture (CLP surgery in male NMRI mice (20-30 g. Pioglitazone (5,10 and 20 mg/kg was administered by gavage daily for 5 days prior to surgery. Nitric oxide involvement was assessed by sub-chronic administration of a non-selective nitric oxide synthase inhibitor, L-NAME and a selective inducible nitric oxide synthase inhibitor, aminoguanidine. TNF-α  and IL-1β plasma levels were measured by ELISA. Pioglitazone (10 and 20 mg/kg significantly improved survival rate in septic mice. The chronic intraperitoneally co-administration of L-NAME (0.5 mg/kg, daily or aminoguanidine (1 mg/kg, daily with a daily dose of pioglitazone, 5 mg/kg, significantly increased the survival rate. This survival improving effect was accompanied by a significant reduction in pro-inflammatory cytokines TNF-α and IL-1β plasma levels. In conclusion, sub-chronic pioglitazone treatment can improve survival in mouse sepsis model by CLP. Inhibition of nitric oxide release, probably through inducible nitric oxide synthase at least in part is responsible for this effect. Suppression of TNF-α and IL-1β could be another mechanism in pioglitazone-induced survival improving effect in septic mice.

  2. The Effects of Sub-Chronic Treatment with Pioglitazone on the Septic Mice Mortality in the Model of Cecal Ligation and Puncture: Involvement of Nitric Oxide Pathway.

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    Shafaroodi, Hamed; Hassanipour, Mahsa; Mousavi, Zahra; Rahimi, Nastaran; Dehpour, Ahmad Reza

    2015-10-01

    Sepsis is a systemic inflammatory response syndrome caused by an infection and remains as a major challenge in health care. Many studies have reported that pioglitazone may display anti-inflammatory effects. This study was designed to evaluate the effect of subchronic treatment with pioglitazone on high-grade septic mice survival and nitrergic system involvement. Diffused sepsis was induced by cecal ligation and puncture (CLP) surgery in male NMRI mice (20-30 g). Pioglitazone (5,10 and 20 mg/kg) was administered by gavage daily for 5 days prior to surgery. Nitric oxide involvement was assessed by sub-chronic administration of a non-selective nitric oxide synthase inhibitor, L-NAME and a selective inducible nitric oxide synthase inhibitor, aminoguanidine. TNF-α  and IL-1β plasma levels were measured by ELISA. Pioglitazone (10 and 20 mg/kg) significantly improved survival rate in septic mice. The chronic intraperitoneally co-administration of L-NAME (0.5 mg/kg, daily) or aminoguanidine (1 mg/kg, daily) with a daily dose of pioglitazone, 5 mg/kg, significantly increased the survival rate. This survival improving effect was accompanied by a significant reduction in pro-inflammatory cytokines TNF-α and IL-1β plasma levels. In conclusion, sub-chronic pioglitazone treatment can improve survival in mouse sepsis model by CLP. Inhibition of nitric oxide release, probably through inducible nitric oxide synthase at least in part is responsible for this effect. Suppression of TNF-α and IL-1β could be another mechanism in pioglitazone-induced survival improving effect in septic mice.

  3. Effects of pioglitazone in familial combined hyperlipidaemia.

    NARCIS (Netherlands)

    Abbink-Zandbergen, E.J.; Graaf, J. de; Haan, J.H.A. de; Heerschap, A.; Stalenhoef, A.F.H.; Tack, C.J.J.

    2006-01-01

    OBJECTIVES: Familial combined hyperlipidaemia (FCH) is associated with insulin resistance. We hypothesized that pioglitazone treatment of FCH patients might increase insulin sensitivity, but may also improve serum lipid levels, body fat distribution, intramyocellular lipids (IMCL) and endothelial fu

  4. Pioglitazone treatment restores in vivo muscle oxidative capacity in a rat model of diabetes

    NARCIS (Netherlands)

    Wessels, B.; Ciapaite, J.; van den Broek, N. M. A.; Houten, S. M.; Nicolay, K.; Prompers, J. J.

    2015-01-01

    Aim: To determine the effect of pioglitazone treatment on in vivo and ex vivo muscle mitochondrial function in a rat model of diabetes. Methods: Both the lean, healthy rats and the obese, diabetic rats are Zucker Diabetic Fatty (ZDF) rats. The homozygous fa/fa ZDF rats are obese and diabetic. The he

  5. Free carnitine and acylcarnitines in obese patients with polycystic ovary syndrome and effects of pioglitazone treatment

    DEFF Research Database (Denmark)

    Vigerust, Natalya Filipchuk; Bohov, Pavol; Bjørndal, Bodil;

    2012-01-01

    To determine fasting and insulin-stimulated levels of carnitine precursors, total and free carnitine, and acylcarnitines, and evaluate the impact of pioglitazone treatment in obese patients with polycystic ovary syndrome (PCOS).......To determine fasting and insulin-stimulated levels of carnitine precursors, total and free carnitine, and acylcarnitines, and evaluate the impact of pioglitazone treatment in obese patients with polycystic ovary syndrome (PCOS)....

  6. Pioglitazone is an effective treatment for patients with post-stroke depression combined with type 2 diabetes mellitus.

    Science.gov (United States)

    Hu, Yaozhi; Xing, Haiyan; Dong, Xiaomeng; Lu, Wenxian; Xiao, Xinxing; Gao, Lilin; Cui, Minghu; Chen, Jinbo

    2015-09-01

    The antidepressive effects of the antidiabetic medicine, pioglitazone, were recently reported in several studies. These effects may ameliorate the depressive symptoms of patients with post-stroke depression (PSD). The present study aimed to evaluate the antidepressive effect of pioglitazone in patients with PSD combined with type 2 diabetes. A total of 118 consecutive patients with stroke who had depression were studied for an average of 3 months. The Diagnostic and Statistical Manual of Mental Disorders (fourth edition) was used to assess whether a patient was depressed or not. The severity of depression was evaluated by the Hamilton depression rating scale (HAMD). In accordance with their HAMD scores, the 118 patients were divided into a severe depression group (n=40) and a mild and moderate (MM) depression group (n=78). These subjects were then divided into pioglitazone [30 mg once daily (qd)] and metformin (0.5 g twice daily) subgroups. All patients were given fluoxetine (20 mg qd). Follow-up evaluations, which included HAMD scores, activities of daily living (ADL) scores, fasting blood glucose (FBG) levels and fasting insulin (FINS) levels, were conducted on the first and third month following the beginning of the treatment. In the MM depression group, the HAMD score in the pioglitazone subgroup was lower than that in the metformin subgroup following treatment for 1 or 3 months. In the severe depression group, the HAMD score in the pioglitazone subgroup was lower than that in the metformin subgroup following 3 months of treatment. The FINS levels of the pioglitazone subgroup gradually decreased in the 3 months of treatment. No noticeable improvement was observed in the ADL scores and FBG values. In conclusion, the results of the current study demonstrate that pioglitazone effectively decreased HAMD scores and FINS values in patients with PSD, suggesting that pioglitazone may be useful for the treatment of patients with PSD combined with type 2 diabetes.

  7. Changes in bone biological markers after treatment of Iranian diabetic patients with pioglitazone: No relation to polymorphism of PPAR-γ (Pro12Ala).

    Science.gov (United States)

    Namvaran, Fatemeh; Rahimi-Moghaddam, Parvaneh; Azarpira, Negar; Dabbaghmanesh, Mohammad Hossien; Bakhshayeshkaram, Marzieh; Namvaran, Mohamad Mahdi

    2013-04-01

    Thiazolidinediones (TZDs) improves insulin sensitivity by activating the peroxisome proliferator-activated receptor γ (PPAR-g). We aimed to study any association between variation in bone biochemical markers and single nucleotide polymorphism (SNP) in PPAR-γ (Pro12Ala) and investigate if these genetic variants affect bone turnover markers in Iranian diabetic population before and after treatment with pioglitazone. A total of 101 patients (type 2 diabetic (T2D) were treated for 12 weeks with pioglitazone (15 mg/day). Bone Biological markers, osteocalcin, and C-terminal telopeptide of type 1 collagen (CTx) were measured before and after pioglitazone therapy. We genotyped 128 nondiabetic controls and 101 T2D patients as well. Pro12Ala polymorphism in PPAR-γ was done by real-time polymerase chain reaction (RT-PCR) using TaqMan assay. There were statistically significant differences in allele frequencies of Pro12Ala while comparing the controls with T2D subjects. Ala frequency was 7 vs 3%, P = 0.036 and genotypic frequency of Pro/Ala was 5.94 vs 14.06%, P = 0.04. After treatment, the homeostasis model of assessment of insulin resistance (HOMA-IR) as a maker of insulin resistance was significantly decreased (P < 0.001). In respect of bone turnover markers, CTx values decreased and osteocalcin significantly increased. (P < 0.001). Our findings did not reveal a significant association between this polymorphism and bone turnover markers after pioglitazone treatment. The reduced insulin resistance might be the reason that CTx values decreased and osteocalcin increased significantly after short-term pioglitazone treatment. These findings suggest the need for further studies on the possible role of insulin in regulation of bone metabolism.

  8. Changes in bone biological markers after treatment of Iranian diabetic patients with pioglitazone: No relation to polymorphism of PPAR-γ (Pro12Ala

    Directory of Open Access Journals (Sweden)

    Fatemeh Namvaran

    2013-01-01

    Full Text Available Background: Thiazolidinediones (TZDs improves insulin sensitivity by activating the peroxisome proliferator-activated receptor γ (PPAR-g. We aimed to study any association between variation in bone biochemical markers and single nucleotide polymorphism (SNP in PPAR-γ (Pro12Ala and investigate if these genetic variants affect bone turnover markers in Iranian diabetic population before and after treatment with pioglitazone. Materials and Methods: A total of 101 patients (type 2 diabetic (T2D were treated for 12 weeks with pioglitazone (15 mg/day. Bone Biological markers, osteocalcin, and C-terminal telopeptide of type 1 collagen (CTx were measured before and after pioglitazone therapy. We genotyped 128 nondiabetic controls and 101 T2D patients as well. Pro12Ala polymorphism in PPAR-γ was done by real-time polymerase chain reaction (RT-PCR using TaqMan assay. Results: There were statistically significant differences in allele frequencies of Pro12Ala while comparing the controls with T2D subjects. Ala frequency was 7 vs 3%, P = 0.036 and genotypic frequency of Pro/Ala was 5.94 vs 14.06%, P = 0.04. After treatment, the homeostasis model of assessment of insulin resistance (HOMA-IR as a maker of insulin resistance was significantly decreased ( P < 0.001. In respect of bone turnover markers, CTx values decreased and osteocalcin significantly increased. ( P < 0.001. Conclusion: Our findings did not reveal a significant association between this polymorphism and bone turnover markers after pioglitazone treatment. The reduced insulin resistance might be the reason that CTx values decreased and osteocalcin increased significantly after short-term pioglitazone treatment. These findings suggest the need for further studies on the possible role of insulin in regulation of bone metabolism.

  9. Effects of long-term pioglitazone treatment on peripheral and central markers of aging.

    Directory of Open Access Journals (Sweden)

    Eric M Blalock

    Full Text Available BACKGROUND: Thiazolidinediones (TZDs activate peroxisome proliferator-activated receptor gamma (PPARgamma and are used clinically to help restore peripheral insulin sensitivity in Type 2 diabetes (T2DM. Interestingly, long-term treatment of mouse models of Alzheimer's disease (AD with TZDs also has been shown to reduce several well-established brain biomarkers of AD including inflammation, oxidative stress and Abeta accumulation. While TZD's actions in AD models help to elucidate the mechanisms underlying their potentially beneficial effects in AD patients, little is known about the functional consequences of TZDs in animal models of normal aging. Because aging is a common risk factor for both AD and T2DM, we investigated whether the TZD, pioglitazone could alter brain aging under non-pathological conditions. METHODS AND FINDINGS: We used the F344 rat model of aging, and monitored behavioral, electrophysiological, and molecular variables to assess the effects of pioglitazone (PIO-Actos(R a TZD on several peripheral (blood and liver and central (hippocampal biomarkers of aging. Starting at 3 months or 17 months of age, male rats were treated for 4-5 months with either a control or a PIO-containing diet (final dose approximately 2.3 mg/kg body weight/day. A significant reduction in the Ca(2+-dependent afterhyperpolarization was seen in the aged animals, with no significant change in long-term potentiation maintenance or learning and memory performance. Blood insulin levels were unchanged with age, but significantly reduced by PIO. Finally, a combination of microarray analyses on hippocampal tissue and serum-based multiplex cytokine assays revealed that age-dependent inflammatory increases were not reversed by PIO. CONCLUSIONS: While current research efforts continue to identify the underlying processes responsible for the progressive decline in cognitive function seen during normal aging, available medical treatments are still very limited

  10. PROactive 07: pioglitazone in the treatment of type 2 diabetes: results of the PROactive study

    Directory of Open Access Journals (Sweden)

    Erl

    2007-09-01

    Full Text Available Erland Erdmann1, John Dormandy2, Robert Wilcox3, Massimo Massi-Benedetti4, Bernard Charbonnel51University of Cologne, Cologne, Germany; 2Department of Clinical Vascular Research, St Georges Hospital, London, UK; 3Department of Cardiovascular Medicine, Queen’s Medical Centre, University Hospital, Nottingham, UK; 4University of Perugia, Medicine and Metabolic Diseases, Perugia, Italy; 5Clinique d’Endocrinologie, Hôtel Dieu, Nantes Cedex 1, FranceAbstract: Patients with type 2 diabetes face an increased risk of macrovascular disease compared to those without. Significant reductions in the risk of major cardiovascular events can be achieved with appropriate drug therapy, although patients with type 2 diabetes remain at increased risk compared with non-diabetics. The thiazolidinedione, pioglitazone, is known to offer multiple, potentially antiatherogenic, effects that may have a beneficial impact on macrovascular outcomes, including long-term improvements in insulin resistance (associated with an increased rate of atherosclerosis and improvement in the atherogenic lipid triad (low HDL-cholesterol, raised triglycerides, and a preponderance of small, dense LDL particles that is observed in patients with type 2 diabetes. The recent PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive study showed that pioglitazone can reduce the risk of secondary macrovascular events in a high-risk patient population with type 2 diabetes and established macrovascular disease. Here, we summarize the key results from the PROactive study and place them in context with other recent outcome trials in type 2 diabetes.Keywords: pioglitazone, macrovascular disease, type 2 diabetes, secondary prevention

  11. Clinical effect of addition of beraprost sodium to pioglitazone treatment on the blood glucose levels in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Chen, T; Kusunoki, M; Sato, D; Tsutsui, H; Nakamura, T; Miyata, T; Oshida, Y

    2013-11-01

    In recent years, the number of patients with type 2 diabetes mellitus caused by insulin resistance has continued to increase in Japan. Insulin resistance is considered to be closely related to the risk of cardiovascular diseases and atherosclerotic diseases, represented by arteriosclerosis obliterans (ASO). Therefore, improvement of insulin resistance is one of the important strategies in the treatment of type 2 diabetes mellitus. At present, α-glucosidase inhibitors, incretin-related drugs, and thiazolidinediones are among the most important oral hypoglycemic drugs used to improve insulin resistance. In this study, the effect of beraprost sodium, a prostaglandin I2 derivative, in the treatment of type 2 diabetes mellitus was investigated. In type 2 diabetic patients with ASO who were under treatment with pioglitazone, additional treatment with beraprost sodium exerted a significant synergistic effect in reducing the serum HbA1c levels as compared to treatment with pioglitazone alone. This result indicates that concomitant administration of pioglitazone and beraprost sodium may be useful in the treatment of diabetes -mellitus.

  12. Improved Insulin Sensitivity during Pioglitazone Treatment Is Associated with Changes in IGF-I and Cortisol Secretion in Type 2 Diabetes and Impaired Glucose Tolerance.

    Science.gov (United States)

    Arnetz, Lisa; Rajamand Ekberg, Neda; Höybye, Charlotte; Brismar, Kerstin; Alvarsson, Michael

    2013-01-01

    Background. Hypercortisolism and type 2 diabetes (T2D) share clinical characteristics. We examined pioglitazone's effects on the GH-IGF-I and HPA axes in men with varying glucose intolerance. Methods. 10 men with T2D and 10 with IGT received pioglitazone 30-45 mg for 12 weeks. OGTT with microdialysis in subcutaneous adipose tissue and 1 μg ACTH-stimulation test were performed before and after. Glucose, insulin, IGF-I, IGFBP1, and interstitial measurements were analyzed during the OGTT. Insulin sensitivity was estimated using HOMA-IR. Results. HOMA-IR improved in both groups. IGF-I was initially lower in T2D subjects (P = 0.004) and increased during treatment (-1.4 ± 0.5 to -0.5 ± 0.4 SD; P = 0.007); no change was seen in IGT (0.4 ± 39 SD before and during treatment). Fasting glycerol decreased in T2D (P = 0.038), indicating reduced lipolysis. Fasting cortisol decreased in T2D (400 ± 30 to 312 ± 25 nmol/L; P = 0.041) but increased in IGT (402 ± 21 to 461 ± 35 nmol/L; P = 0.044). Peak cortisol was lower in T2D during treatment (599 ± 32 to 511 ± 43, versus 643 ± 0.3 to 713 ± 37 nmol/L in IGT; P = 0.007). Conclusions. Pioglitazone improved adipose tissue and liver insulin sensitivity in both groups. This may explain increased IGF-I in T2D. Pioglitazone affected cortisol levels in both groups but differently, suggesting different mechanisms for improving insulin sensitivity between T2D and IGT.

  13. Alogliptin in combination with metformin and pioglitazone for the treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Holland, Daniel Q; Neumiller, Joshua J

    2014-01-01

    Alogliptin is a selective dipeptidyl peptidase-4 inhibitor recently marketed for once-daily administration in the treatment of type 2 diabetes mellitus (T2DM). Fixed-dose combinations of alogliptin with both metformin and pioglitazone are also commercially available, providing a measure of convenience in addition to an effective mode of delivering combination therapy to improve glycemic control. Alogliptin has been studied clinically as initial therapy in treatment-naïve patients with T2DM and as initial therapy or add-on in combination with other antidiabetic agents. Clinical trial data with alogliptin demonstrate clinical efficacy in terms of glycosylated hemoglobin A1c and fasting plasma glucose reductions when used both as monotherapy and as a component of two- or three-drug combination regimens for the treatment of T2DM. Extensive Phase II and Phase III clinical trial data support the use of alogliptin in combination with metformin and pioglitazone. Glycemic reduction with both combinations is similar to the sum of the respective monotherapies, with adverse event rates similar - or more moderate - than those observed with up-titration of monotherapy or the addition of other antihyperglycemic agents.

  14. Pioglitazone does not increase the risk of type II diabetes in patients with bladder cancer: A retrospective study.

    Science.gov (United States)

    Dong, Youhong; Wang, Anping

    2016-07-01

    The aim of the retrospective study was to analyze the effect of pioglitazone on the expression of tumor tissue inflammation factor interleukin (IL)-8, macrophage colony-stimulating factor (M-CSF) and vascular endothelial growth factor (VEGF) of type II diabetes in bladder cancer patients. In addition, whether there was a correlation between pioglitazone and the occurrence of male bladder cancer was also investigated. In total, 42 male cases diagnosed with type II diabetes secondary to bladder cancer were selected. Forty male cases, with simplex type II diabetes but not with bladder cancer, served as the control. Tumor biopsy specimens were collected to detect the expression levels of IL-8, M-CSF and VEGF. The results showed that the expression of IL-8, M-CSF and VEGF of the simplex diabetes group was significantly lower than that of the secondary to tumor group (Ppioglitazone, duration of diabetes, average fasting blood sugar and glycated hemoglobin levels, was not statistically significant. Multivariable logistic regression analysis revealed that the expression levels of IL-8, M-CSF and VEGF were independent risk factors for the occurrence of bladder cancer (Ppioglitazone (P>0.05). In conclusion, oral pioglitazone may not increase the risk of type II diabetes patients with bladder cancer. However, the occurrence of bladder cancer be associated with the increasing expression levels of IL-8, M-CSF and VEGF.

  15. Pioglitazone Improves Survival In Patients With Cancer: The Hypothesis

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    Banshi Saboo

    2015-12-01

    Full Text Available Pioglitazone is currently the only thiazolidinedione approved by regulatory agencies worldwide for the treatment of type 2 diabetes mellitus (T2DM. The use of pioglitazone in patients with T2DM has been limited because earlier studies showed moderate weight gain and an increased incidence of heart failure, osteoporotic fractures, and bladder cancer. However, new studies have shown that pioglitazone improves both systolic and diastolic left ventricular function and that there is no association between pioglitazone and bladder cancer. Furthermore, pioglitazone is associated with a reduced risk of all-cause mortality in patients with T2DM. Pioglitazone was also found to reduce the incidence of lung, head and neck, breast, colorectal, and hepatocellular cancer. There is tremendous preclinical evidence that links thiazolidinediones with anti-cancer effects. Three possible mechanisms of anti-proliferative effects induced by peroxisome proliferator activated receptor gamma (PPARG agonists emerge: 1 activation of PPARG and epidermal growth factor receptor, which actives several intracellular pathways involved in carcinogenesis; 2 increase in serum adiponectin levels and decrease in serum leptin levels, which are associated with lower cancer risk and more favorable outcomes in patients with cancer; 3 modulate insulin-like growth factor 1 (IGF-1 receptor signaling by decreasing IGF-1 levels and increasing the expression of IGF binding protein 1. To date, there are no prospective, placebo-controlled trials that have analyzed the efficacy of pioglitazone in chemotherapy and chemoprevention. Only one ongoing study has shown that pioglitazone has an excellent capability of eradicating quiescent leukemia stem cells in patients with chronic myeloid leukemia and achieving a complete molecular response. Current evidence supports our theory that future case-control studies examining pioglitazone as chemotherapy, or adjuvant chemotherapy, should be performed in

  16. A review of pioglitazone HCL and glimepiride in the treatment of type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Mozhgan Dorkhan

    2007-11-01

    Full Text Available Mozhgan Dorkhan, Anders FridDepartment of Clinical Sciences, Division of Diabetes and Endocrinology, Lund University, Malmö University Hospital, SwedenAbstract: Type 2 diabetes (T2D is a progressive disorder with a consistent and steady increase in glycosylated hemoglobin (HbA1c over time associated with enhanced risk of micro- and macrovascular complications and a substantial reduction in life expectancy. There are three major pathophysiologic abnormalities associated with T2D: impaired insulin secretion, excessive hepatic glucose output, and insulin resistance in skeletal muscle, liver, and adipose tissue. These defects have been treated in clinical praxis by use of oral insulin secretagogues (sulfonylureas/glinides or insulin, biguanides, and thiazolidinediones (TZDs respectively. Pioglitazone HCL is an insulin sensitizer in the TZD family and glimepiride is an insulin secretagogue in the SU family. This article reviews mechanisms of action and clinical data behind the use of these two commonly used oral hypoglycemic agents with documented efficacy and good safety profile of once-daily administration, alone or in combination with insulin or metformin, in the management of T2D in terms of glycemic and non-glycemic effects, tolerability and side effects, and impact on vascular health.Keywords: pioglitazone, glimepiride, type 2 diabetes, thiazolidinediones, sulfonylureas

  17. Metabolic and other effects of pioglitazone as an add-on therapy to metformin in the treatment of polycystic ovary syndrome (PCOS).

    Science.gov (United States)

    Valsamakis, Georgios; Lois, Kostas; Kumar, Sudhesh; Mastorakos, George

    2013-01-01

    Insulin resistance is a key pathogenic defect of the clustered metabolic disturbances seen in polycystic ovary syndrome (PCOS). Metformin is an insulin sensitizer acting in the liver and the peripheral tissues that ameliorates the metabolic and reproductive defects in PCOS. In addition, pioglitazone is an insulin sensitizer used in diabetes mellitus type 2 (T2DM), improving insulin resistance (IR) in adipose tissue and muscles. In T2DM, these drugs are also used as a combined treatment due to their "add-on effect" on insulin resistance. Although the beneficial role of troglitazone (a member of the thiazolidinediones (TZDs) family) in PCOS has been shown in the past, currently only pioglitazone is available in the market. A few small randomized controlled trials have directly compared the effectiveness of pioglitazone in women with PCOS, while there are a limited number of small studies that support the beneficial metabolic add-on effect of pioglitazone on metformin-treated PCOS women as compared to metformin or pioglitazone monotherapy. These findings suggest a potentially promising role for combined pioglitazone/metformin treatment in the management of PCOS in metformin-resistant patients. In view of recent concerns regarding pioglitazone usage and its associated health risk, we aim to compare the pros and cons of each drug regarding their metabolic and other hormonal effects in women with PCOS and to explore the possible beneficial effect of combined therapy in certain cases, taking into consideration the teratogenic effect of pioglitazone. Finally, we discuss the need for a randomized controlled trial that will evaluate the metabolic and other hormonal effects of combined metformin/pioglitazone treatment in PCOS with selective treatment targets.

  18. Effects and Potential Mechanisms of Pioglitazone on Lipid Metabolism in Obese Diabetic KKAy Mice

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    Jun Peng

    2014-01-01

    Full Text Available This study aimed to analyze the effects and potential mechanisms of pioglitazone on triglyceride and cholesterol metabolism in obese diabetic KKAy mice. Pioglitazone was orally administered to KKAy mice over 30 days. Compared to C57BL/6J mice, KKAy mice developed obvious insulin resistance, hepatic steatosis, and hyperlipidemia. Pioglitazone treatment resulted in deteriorated microvesicular steatosis and elevated hepatic triglyceride levels, though plasma triglyceride and free fatty acid levels were reduced by the treatment, compared to nontreated KKAy mice. Plasma alanine aminotransferase activities were also significantly increased. Additionally, pioglitazone increased plasma concentrations of total cholesterol, HDL-cholesterol, and LDL-cholesterol but decreased hepatic cholesterol. Gene expression profiling revealed that pioglitazone stimulated hepatic peroxisome proliferator-activated receptor gamma hyperactivity, and induced the upregulation of adipocyte-specific and lipogenesis-related genes but downregulated of genes involved in triglyceride lipolysis and fatty acid β-oxidation. Pioglitazone also regulated the genes expression of hepatic cholesterol uptake and excretion, such as low density lipoprotein receptor (LDL-R and scavenger receptor type-BI (SR-BI. These results suggested that pioglitazone could induce excessive hepatic triglyceride accumulation, thus aggravating liver steatosis and lesions in KKAy mice. Furthermore, pioglitazone may suppress the clearance of serum cholesterol from the liver predominantly through inhibition of LDL-R and SR-BI expression, thus increasing the plasma cholesterol.

  19. Impaired insulin activation and dephosphorylation of glycogen synthase in skeletal muscle of women with polycystic ovary syndrome is reversed by pioglitazone treatment

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Højlund, Kurt; Andersen, Nicoline Resen

    2008-01-01

    . No significant abnormalities in GSK-3alpha or -3beta were found in PCOS subjects. Pioglitazone treatment improved insulin-stimulated glucose metabolism and GS activity in PCOS (all P ... of GS including absent dephosphorylation at sites 2+2a contributes to insulin resistance in skeletal muscle in PCOS. The ability of pioglitazone to enhance insulin sensitivity, in part, involves improved insulin action on GS activity and dephosphorylation at NH2-terminal sites....

  20. Pioglitazone has a dubious bladder cancer risk but an undoubted cardiovascular benefit.

    Science.gov (United States)

    Ryder, R E J

    2015-03-01

    On 8 April 2014, a US jury ordered Takeda and Eli Lilly to pay $9 bn in punitive damages after finding that they had concealed the cancer risks associated with pioglitazone. By contrast, on 28 August 2014, the long-awaited outcome of the 10-year Kaiser Permanente Northern California study was announced. That study was specifically designed to investigate whether patients exposed to pioglitazone were at an increased risk of bladder cancer and found no association; thus, at last, the controversial issue has been resolved. A review, in retrospect, of the story of the proposed link between pioglitazone and bladder cancer reveals flaws at every stage. In 2012, a BMJ editorial, in keeping with some other contemporary reports, stated 'it can confidently be assumed that pioglitazone increases the risk of bladder cancer'. Examination of the information which led to such a statement shows that: 1) the pre-clinical findings of bladder cancer in male rats is not indicative of human risk; 2) there is no association between bladder cancer and pioglitazone in randomized controlled trials, once cases that could not plausibly be related to treatment are removed; and 3) the observational studies that have suggested a link have over-extrapolated from the data: pioglitazone-treated patients had more risk factors for bladder cancer than those not treated with pioglitazone. Meanwhile careful study of randomized controlled trials shows evidence of cardiovascular benefit from pioglitazone in Type 2 diabetes, a condition which results, more than anything, in premature cardiovascular death and morbidity.

  1. Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo.

    Science.gov (United States)

    Bogacka, Iwona; Xie, Hui; Bray, George A; Smith, Steven R

    2005-05-01

    Thiazolidenediones such as pioglitazone improve insulin sensitivity in diabetic patients by several mechanisms, including increased uptake and metabolism of free fatty acids in adipose tissue. The purpose of the present study was to determine the effect of pioglitazone on mitochondrial biogenesis and expression of genes involved in fatty acid oxidation in subcutaneous fat. Patients with type 2 diabetes were randomly divided into two groups and treated with placebo or pioglitazone (45 mg/day) for 12 weeks. Mitochondrial DNA copy number and expression of genes involved in mitochondrial biogenesis were quantified by real-time PCR. Pioglitazone treatment significantly increased mitochondrial copy number and expression of factors involved in mitochondrial biogenesis, including peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1alpha and mitochondrial transcription factor A. Treatment with pioglitazone stimulated the expression of genes in the fatty acid oxidation pathway, including carnitine palmitoyltransferase-1, malonyl-CoA decarboxylase, and medium-chain acyl-CoA dehydrogenase. The expression of PPAR-alpha, a transcriptional regulator of genes encoding mitochondrial enzymes involved in fatty acid oxidation, was higher after pioglitazone treatment. Finally, the increased mitochondrial copy number and the higher expression of genes involved in fatty acid oxidation in human adipocytes may contribute to the hypolipidemic effects of pioglitazone.

  2. Pioglitazone for the treatment of type 2 diabetes in patients inadequately controlled on insulin

    Directory of Open Access Journals (Sweden)

    Stanley S Schwartz

    2010-07-01

    Full Text Available Stanley S SchwartzDiabetes Disease Management at the University of Pennsylvania, Penn Presbyterian Medical Center, Philadelphia Heart Institute, Philadelphia, Pennsylvania, USAAbstract: Insulin resistance and impaired beta-cell function are primary defects that occur early in the course of development of type 2 diabetes. Insulin resistance leads to hyperinsulinemia in order to maintain normal glucose tolerance. In most cases of type 2 diabetes, beta-cell dysfunction develops subsequent to the development of insulin resistance, and it is not until such beta-cell dysfunction develops that any abnormality in glucose tolerance is seen. Insulin resistance is a primary defect in type 2 diabetes. The risk of coronary heart disease is significantly increased in patients with type 2 diabetes. Cardiovascular disease causes 80% of all diabetic mortality, and in 75% of those cases, it is a result of coronary atherosclerosis. These points provide a rationale for early and aggressive management of cardiovascular risk in patients with diabetes. Thiazolidinediones represent an effective tool for targeting some features of this increased risk as they decrease insulin resistance and can prevent and/or delay diabetes progression.Keywords: pioglitazone, type 2 diabetes, insulin

  3. Three-month treatment with pioglitazone reduces circulating C1q-binding adiponectin complex to total-adiponectin ratio, without changes in body mass index, in people with type 2 diabetes.

    Science.gov (United States)

    Nakatsuji, Hideaki; Kishida, Ken; Kobayashi, Hironori; Funahashi, Tohru; Shimomura, Iichiro

    2013-01-01

    We measured circulating C1q-binding adiponectin (C1q-APN) levels before and after 3-month treatment with pioglitazone in people with type 2 diabetes. The results indicate 3-month treatment with pioglitazone reduces circulating levels of C1q-APN/total-adiponectin ratio without changes in body mass index.

  4. Improved insulin sensitivity and adipose tissue dysregulation after short-term treatment with pioglitazone in non-diabetic, insulin-resistant subjects.

    Science.gov (United States)

    Hammarstedt, A; Sopasakis, V Rotter; Gogg, S; Jansson, P-A; Smith, U

    2005-01-01

    We examined whether short-term treatment with a thiazolidinedione improves insulin sensitivity in non-obese but insulin-resistant subjects and whether this is associated with an improvement in dysregulated adipose tissue (reduced expression of IRS-1, GLUT4, PPARgamma co-activator 1 and markers of terminal differentiation) that we have previously documented to be associated with insulin resistance. Ten non-diabetic subjects, identified as having low IRS-1 and GLUT-4 protein in adipose cells as markers of insulin resistance, underwent 3 weeks of treatment with pioglitazone. The euglycaemic-hyperinsulinaemic clamp technique was used to measure insulin sensitivity before and after treatment. Serum samples were analysed for glucose, insulin, lipids, total and high-molecular-weight (HMW) adiponectin levels. Biopsies from abdominal subcutaneous adipose tissue were taken, cell size measured, mRNA and protein extracted and quantified using real-time RT-PCR and Western blot. Insulin sensitivity was improved after 3 weeks treatment and circulating total as well as HMW adiponectin increased in all subjects, while no effect was seen on serum lipids. In the adipose cells, gene and protein expression of IRS-1 and PPARgamma co-activator 1 remained unchanged, while adiponectin, adipocyte P 2, uncoupling protein 2, GLUT4 and liver X receptor-alpha increased. Insulin-stimulated tyrosine phosphorylation and p-ser-PKB/Akt increased, while no significant effect of thiazolidinedione treatment was seen on the inflammatory status of the adipose tissue in these non-obese subjects. Short-term treatment with pioglitazone improved insulin sensitivity in the absence of any changes in circulating NEFA or lipid levels. Several markers of adipose cell differentiation, previously shown to be reduced in insulin resistance, were augmented, supporting the concept that insulin resistance in these individuals is associated with impaired terminal differentiation of the adipose cells.

  5. Beneficial effects of canagliflozin in combination with pioglitazone on insulin sensitivity in rodent models of obese type 2 diabetes.

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    Yoshinori Watanabe

    Full Text Available Despite its insulin sensitizing effects, pioglitazone may induce weight gain leading to an increased risk of development of insulin resistance. A novel sodium glucose co-transporter 2 (SGLT2 inhibitor, canagliflozin, provides not only glycemic control but also body weight reduction through an insulin-independent mechanism. The aim of this study was to investigate the combined effects of these agents on body weight control and insulin sensitivity.Effects of combination therapy with canagliflozin and pioglitazone were evaluated in established diabetic KK-Ay mice and prediabetic Zucker diabetic fatty (ZDF rats.In the KK-Ay mice, the combination therapy further improved glycemic control compared with canagliflozin or pioglitazone monotherapy. Furthermore, the combination significantly attenuated body weight and fat gain induced by pioglitazone and improved hyperinsulinemia. In the ZDF rats, early intervention with pioglitazone monotherapy almost completely prevented the progressive development of hyperglycemia, and no further improvement was observed by add-on treatment with canagliflozin. However, the combination significantly reduced pioglitazone-induced weight gain and adiposity and improved the Matsuda index, suggesting improved whole-body insulin sensitivity.Our study indicates that combination therapy with canagliflozin and pioglitazone improves insulin sensitivity partly by preventing glucotoxicity and, at least partly, by attenuating pioglitazone-induced body weight gain in two different obese diabetic animal models. This combination therapy may prove to be a valuable option for the treatment and prevention of obese type 2 diabetes.

  6. Beneficial effects of canagliflozin in combination with pioglitazone on insulin sensitivity in rodent models of obese type 2 diabetes.

    Science.gov (United States)

    Watanabe, Yoshinori; Nakayama, Keiko; Taniuchi, Nobuhiko; Horai, Yasushi; Kuriyama, Chiaki; Ueta, Kiichiro; Arakawa, Kenji; Senbonmatsu, Takaaki; Shiotani, Masaharu

    2015-01-01

    Despite its insulin sensitizing effects, pioglitazone may induce weight gain leading to an increased risk of development of insulin resistance. A novel sodium glucose co-transporter 2 (SGLT2) inhibitor, canagliflozin, provides not only glycemic control but also body weight reduction through an insulin-independent mechanism. The aim of this study was to investigate the combined effects of these agents on body weight control and insulin sensitivity. Effects of combination therapy with canagliflozin and pioglitazone were evaluated in established diabetic KK-Ay mice and prediabetic Zucker diabetic fatty (ZDF) rats. In the KK-Ay mice, the combination therapy further improved glycemic control compared with canagliflozin or pioglitazone monotherapy. Furthermore, the combination significantly attenuated body weight and fat gain induced by pioglitazone and improved hyperinsulinemia. In the ZDF rats, early intervention with pioglitazone monotherapy almost completely prevented the progressive development of hyperglycemia, and no further improvement was observed by add-on treatment with canagliflozin. However, the combination significantly reduced pioglitazone-induced weight gain and adiposity and improved the Matsuda index, suggesting improved whole-body insulin sensitivity. Our study indicates that combination therapy with canagliflozin and pioglitazone improves insulin sensitivity partly by preventing glucotoxicity and, at least partly, by attenuating pioglitazone-induced body weight gain in two different obese diabetic animal models. This combination therapy may prove to be a valuable option for the treatment and prevention of obese type 2 diabetes.

  7. Beneficial Effects of Canagliflozin in Combination with Pioglitazone on Insulin Sensitivity in Rodent Models of Obese Type 2 Diabetes

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    Watanabe, Yoshinori; Nakayama, Keiko; Taniuchi, Nobuhiko; Horai, Yasushi; Kuriyama, Chiaki; Ueta, Kiichiro; Arakawa, Kenji; Senbonmatsu, Takaaki; Shiotani, Masaharu

    2015-01-01

    Background Despite its insulin sensitizing effects, pioglitazone may induce weight gain leading to an increased risk of development of insulin resistance. A novel sodium glucose co-transporter 2 (SGLT2) inhibitor, canagliflozin, provides not only glycemic control but also body weight reduction through an insulin-independent mechanism. The aim of this study was to investigate the combined effects of these agents on body weight control and insulin sensitivity. Methods Effects of combination therapy with canagliflozin and pioglitazone were evaluated in established diabetic KK-Ay mice and prediabetic Zucker diabetic fatty (ZDF) rats. Results In the KK-Ay mice, the combination therapy further improved glycemic control compared with canagliflozin or pioglitazone monotherapy. Furthermore, the combination significantly attenuated body weight and fat gain induced by pioglitazone and improved hyperinsulinemia. In the ZDF rats, early intervention with pioglitazone monotherapy almost completely prevented the progressive development of hyperglycemia, and no further improvement was observed by add-on treatment with canagliflozin. However, the combination significantly reduced pioglitazone-induced weight gain and adiposity and improved the Matsuda index, suggesting improved whole-body insulin sensitivity. Conclusions Our study indicates that combination therapy with canagliflozin and pioglitazone improves insulin sensitivity partly by preventing glucotoxicity and, at least partly, by attenuating pioglitazone-induced body weight gain in two different obese diabetic animal models. This combination therapy may prove to be a valuable option for the treatment and prevention of obese type 2 diabetes. PMID:25615826

  8. Pioglitazone Lowers Serum Retinol Binding Protein 4 by Suppressing its Expression in Adipose Tissue of Obese Rats

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    Chaoyu Zhu

    2015-01-01

    Full Text Available Background/Aims: Pioglitazone, a peroxisome proliferator-activated receptor γ activator, is clinically used to treat insulin resistance. However, the underlying mechanism of pioglitazone's action remains unclear. We investigated whether, and how, pioglitazone modulates serum level of retinol binding protein 4 (RBP4, an adipocytokine associated with obesity and insulin resistance. Methods: Insulin sensitivity was determined by oral glucose tolerance test, and RBP4 expression was detected by RT-PCR and Western blotting. Results: Pioglitazone treatment significantly decreased serum RBP4 levels in obese rats, which was correlated with reduced body weight and increased insulin sensitivity. Moreover, pioglitazone greatly decreased RBP4 mRNA and protein levels in adipose tissue but not in the liver. Consistently, pioglitazone treatment significantly reduced RBP4 protein expression in 3T3-L1 adipocytes but not in HepG2 cells. Conclusion: These results demonstrate that pioglitazone inhibits the level of serum RPB4 by suppressing RBP4 expression in adipose tissue of obese rats, suggesting that inhibiting RBP4 expression in adipocytes may provide a mechanism by which pioglitazone improves insulin sensitivity in insulin-resistant subjects.

  9. Modification of MCF-10A cells with pioglitazone and serum-rich growth medium increases soluble factors in the conditioned medium, likely reducing BT-474 cell growth.

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    Khoo, Boon Yin; Miswan, Noorizan; Balaram, Prabha; Nadarajan, Kalpanah; Elstner, Elena

    2012-01-01

    In the present study, we aimed to preincubate MCF-10A cells with pioglitazone and/or serum-rich growth media and to determine adhesive and non-adhesive interactions of the preincubated MCF-10A cells with BT-474 cells. For this purpose, the MCF-10A cells were preincubated with pioglitazone and/or serum-rich growth media, at appropriate concentrations, for 1 week. The MCF-10A cells preincubated with pioglitazone and/or serum-rich growth media were then co-cultured adhesively and non-adhesively with BT-474 cells for another week. Co-culture of BT-474 cells with the preincubated MCF-10A cells, both adhesively and non-adhesively, reduced the growth of the cancer cells. The inhibitory effect of the preincubated MCF-10A cells against the growth of BT-474 cells was likely produced by increasing levels of soluble factors secreted by the preincubated MCF-10A cells into the conditioned medium, as immunoassayed by ELISA. However, only an elevated level of a soluble factor distinguished the conditioned medium collected from the MCF-10A cells preincubated with pioglitazone and serum-rich growth medium than that with pioglitazone alone. This finding was further confirmed by the induction of the soluble factor transcript expression in the preincubated MCF-10A cells, as determined using real-time PCR, for the above phenomenon. Furthermore, modification of the MCF-10A cells through preincubation did not change the morphology of the cells, indicating that the preincubated cells may potentially be injected into mammary fat pads to reduce cancer growth in patients or to be used for others cell-mediated therapy.

  10. The effect of pioglitazone on aldosterone and cortisol production in HAC15 human adrenocortical carcinoma cells.

    Science.gov (United States)

    Pan, Zhi-qiang; Xie, Ding; Choudhary, Vivek; Seremwe, Mutsa; Tsai, Ying-Ying; Olala, Lawrence; Chen, Xunsheng; Bollag, Wendy B

    2014-08-25

    Pioglitazone belongs to the class of drugs called thiazolidinediones (TZDs), which are widely used as insulin sensitizers in the treatment of diabetes. A major side effect of TZDs is fluid retention. The steroid hormone aldosterone also promotes sodium and fluid retention; however, the effect of pioglitazone on aldosterone production is controversial. We analyzed the effect of pioglitazone alone and in combination with angiotensin II (AngII) on the late rate-limiting step of adrenocortical steroidogenesis in human adrenocortical carcinoma HAC15 cells. Treatment with pioglitazone for 24 h significantly increased the expression of CYP11B2 and enhanced AngII-induced CYP11B2 expression. Despite the observed changes in mRNA levels, pioglitazone significantly inhibited AngII-induced aldosterone production and CYP11B2 protein levels. On the other hand, pioglitazone stimulated the expression of the unfolded protein response (UPR) marker DDIT3, with this effect occurring at early times and inhibitable by the PPARγ antagonist GW9962. The levels of DDIT3 (CHOP) and phospho-eIF2α (Ser51), a UPR-induced event that inhibits protein translation, were also increased. Thus, pioglitazone promotes CYP11B2 expression but nevertheless inhibits aldosterone production in AngII-treated HAC15 cells, likely by blocking global protein translation initiation through DDIT3 and phospho-eIF2α. In contrast, pioglitazone promoted AngII-induced CYP11B1 expression and cortisol production. Since cortisol enhances lipolysis, this result suggests the possibility that PPARs, activated by products of fatty acid oxidation, stimulate cortisol secretion to promote utilization of fatty acids during fasting. In turn, the ability of pioglitazone to stimulate cortisol production could potentially underlie the effects of this drug on fluid retention.

  11. Pioglitazone ameliorates the lowered exercise capacity and impaired mitochondrial function of the skeletal muscle in type 2 diabetic mice.

    Science.gov (United States)

    Takada, Shingo; Hirabayashi, Kagami; Kinugawa, Shintaro; Yokota, Takashi; Matsushima, Shouji; Suga, Tadashi; Kadoguchi, Tomoyasu; Fukushima, Arata; Homma, Tsuneaki; Mizushima, Wataru; Masaki, Yoshihiro; Furihata, Takaaki; Katsuyama, Ryoichi; Okita, Koichi; Tsutsui, Hiroyuki

    2014-10-05

    We have reported that exercise capacity is reduced in high fat diet (HFD)-induced diabetic mice, and that this reduction is associated with impaired mitochondrial function in skeletal muscle (SKM). However, it remains to be clarified whether the treatment of diabetes ameliorates the reduced exercise capacity. Therefore, we examined whether an insulin-sensitizing drug, pioglitazone, could improve exercise capacity in HFD mice. C57BL/6J mice were fed a normal diet (ND) or HFD, then treated with or without pioglitazone (3 mg/kg/day) to yield the following 4 groups: ND+vehicle, ND+pioglitazone, HFD+vehicle, and HFD+pioglitazone (n=10 each). After 8 weeks, body weight, plasma glucose, and insulin in the HFD+vehicle were significantly increased compared to the ND+vehicle group. Pioglitazone normalized the insulin levels in HFD-fed mice, but did not affect the body weight or plasma glucose. Exercise capacity determined by treadmill tests was significantly reduced in the HFD+vehicle, and this reduction was almost completely ameliorated in HFD+pioglitazone mice. ADP-dependent mitochondrial respiration, complex I and III activities, and citrate synthase activity were significantly decreased in the SKM of the HFD+vehicle animals, and these decreases were also attenuated by pioglitazone. NAD(P)H oxidase activity was significantly increased in the HFD+vehicle compared with the ND+vehicle, and this increase was ameliorated in HFD+pioglitazone mice. Pioglitazone improved the exercise capacity in diabetic mice, which was due to the improvement in mitochondrial function and attenuation of oxidative stress in the SKM. Our data suggest that pioglitazone may be useful as an agent for the treatment of diabetes mellitus.

  12. COMPARISON OF METFORMIN AND PIOGLITAZONE IN PCOS

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    Archana V.

    2013-04-01

    Full Text Available ABSTRACT: OBJECTIVES: To compare and evaluate the effects of metformin and pioglitazone on insulin resistance, ovulation and hyperandrogenis m in women with PCOS. METHODS: Total 180 patients were included in this double blind cont rolled trial between 18 to 30 years. These women were randomly allocated in two groups. After t aking written consent they were treated with either metformin or pioglitazone for 6 months a nd pretreatment versus post treatment clinical and biochemical variables were analysed an d compared. RESULTS: After treatment with metformin and pioglitazone around 50- 55 % women in both group achieved menstrual cycle regularity , and ovulation was restored in 44 % and 55 % in patients on metformin and pioglitazone respectively. Both group showed decline i n F-G score. Decrease in serum cholesterol was seen in both groups , but was more pr onounced with pioglitazone. Effect on insulin resistance and hyperinsulinemia was assessed by measuring pre and post treatment fasting serum insulin levels . Fall in serum insuli n level was more with pioglitazone and 48 % women became normoinsulinemic after treatment with pioglitazone as compared to 12 % with metformin. Rise in serum SHBG and fall in LH level was more remarkable with pioglitazone (p value < 0.05.

  13. Pioglitazone improves the cardio-ankle vascular index in patients with type 2 diabetes mellitus treated with metformin

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    Ohira M

    2014-07-01

    Full Text Available Masahiro Ohira,1 Takashi Yamaguchi,1 Atsuhito Saiki,1 Noriko Ban,1 Hidetoshi Kawana,1 Ayako Nagumo,1 Takeyoshi Murano,2 Kohji Shirai,3 Ichiro Tatsuno1 1Center for Diabetes, Endocrinology and Metabolism, 2Department of Clinical Laboratory Medicine, 3Department of Vascular Function, Sakura Hospital, Toho University Medical Center, Chiba, Japan Background: Type 2 diabetes is known to be associated with elevated cardiovascular mortality. Pioglitazone improves blood pressure (BP and pulse wave velocity (PWV, which is an arterial stiffness parameter. Arterial stiffness is closely associated with cardiovascular disease. However, PWV is correlated with BP. The cardio-ankle vascular index (CAVI reflects arterial stiffness independent of BP. Pioglitazone improves PWV but reduces blood pressure. The aim of this study was to re-evaluate the effect of pioglitazone on arterial stiffness with CAVI. Methods: Sixty patients with type 2 diabetes mellitus and already on 500 mg/day of metformin received add-on therapy of pioglitazone 15 mg/day or glimepiride 1 mg/day for 6 months, during which time changes in their metabolic parameters and CAVI were observed. Results: After 6 months of treatment, both pioglitazone (n=30 and glimepiride (n=30 improved fasting blood glucose and glycated hemoglobin. The changes in fasting blood glucose and glycated hemoglobin between the two groups were greater in the pioglitazone group. Systolic and diastolic BP was decreased in both groups, with no significant between-group differences. Only pioglitazone increased serum adiponectin levels, and the change in adiponectin between the pioglitazone and glimepiride groups was significantly different. CAVI was decreased significantly by pioglitazone but remained unchanged after treatment with glimepiride. The change in CAVI between the two groups was significantly different. Conclusion: These results suggest that pioglitazone improves CAVI, a BP-independent arterial stiffness parameter

  14. Pioglitazone Improves Mitochondrial Function in the Remnant Kidney and Protects against Renal Fibrosis in 5/6 Nephrectomized Rats

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    Li Sun

    2017-08-01

    Full Text Available Pioglitazone is a type of peroxisome proliferator-activated receptor γ (PPARγ agonist and has been demonstrated to be effective in chronic kidney diseases (CKD treatment. However, the underlying mechanism involved in the renoprotection of pioglitazone has not been fully revealed. In the present study, the renoprotective mechanism of pioglitazone was investigated in 5/6 nephrectomized (Nx rats and TGF-β1-exposed HK-2 cells. Pioglitazone attenuated renal injury and improved renal function, as examined by 24 h urinary protein, blood urea nitrogen and plasma creatinine in Nx rats. Renal fibrosis and enhanced expressions of profibrotic proteins TGF-β1, fibronectin and collagen I caused by Nx were significantly alleviated by pioglitazone. In addition, pioglitazone protected mitochondrial functions by stabilizing the mitochondrial membrane potential, inhibiting ROS generation, maintaining ATP production and the activities of complexes I and III, and preventing cytochrome C leakage from mitochondria. Pioglitazone also upregulated the expression levels of ATP synthase β, COX I and NDUFB8, which were downregulated in the kidney of Nx rats and TGF-β1-exposed HK-2 cells. Furthermore, pioglitazone increased fusion proteins Opa-1 and Mfn2 expressions and decreased fission protein Drp1 expression. The results imply that pioglitazone may exert the renoprotective effects through modulating mitochondrial electron transport chain and mitochondrial dynamics in CKD. Finally, these recoveries were completely or partly inhibited by GW9662, which suggests that these effects at least partly PPARγ dependent. This study provides evidence for the pharmacological mechanism of pioglitazone in the treatment of CKD.

  15. Polymorphism of adiponectin (45T/G) and adiponectin receptor-2 (795G/A) in an Iranian population: relation with insulin resistance and response to treatment with pioglitazone in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Namvaran, Fatemeh; Rahimi-Moghaddam, Parvaneh; Azarpira, Negar; Dabbaghmanesh, Mohammad Hosein

    2012-05-01

    Adiponectin, an adipose-derived plasma protein, is reduced in patients with obesity and type 2 diabetes. Thiazolidinediones can increase adiponectin levels and improve insulin sensitivity. This study investigated the associations between type 2 diabetes and two single-nucleotide polymorphisms in the adiponectin (45T/G) and adiponectin receptor-2 gene (795G/A), and investigated whether these genetic variants affect the response to pioglitazone in Iranian patients with type 2 diabetes. We genotyped 128 non-diabetic participants and 101 patients with type 2 diabetes for 45T/G and 795G/A with polymerase chain reaction-restriction fragment length polymorphism assays. Patients were treated with pioglitazone for 12 weeks, after which we compared laboratory parameters in these two groups. Fasting blood sugar differed significantly in individuals with different 795G/A genotypes after pioglitazone treatment (P = 0.009). The mean decrease in insulin/glucose ratio after treatment also differed significantly in individuals with different 45T/G genotypes (P = 0.035). The T allele frequency for 45T/G was 87.11% in controls versus 81.68% in patients (P = 0.071). The TG and GG genotypes were more frequent in patients (P = 0.032). The G allele frequency for 795G/A was 76.17% in controls versus 80.20% in patients (P = 0.179). 795G/A variants were not significantly different between patient and control group. The adiponectin gene 45T/G mutation may be an important determinant of type 2 diabetes in the Iranian population. However, adiponectin 45T/G and adiponectin receptor-2 795G/A polymorphisms were not significantly associated with the response to pioglitazone in our sample.

  16. Current clinical evidence on pioglitazone pharmacogenomics

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    Marina eKawaguchi-Suzuki

    2013-11-01

    Full Text Available Pioglitazone is the most widely used thiazolidinedione and acts as an insulin-sensitizer through activation of the Peroxisome Proliferator-Activated Receptor-γ (PPARγ. Pioglitazone is approved for use in the management of type 2 diabetes mellitus, but its use in other therapeutic areas is increasing due to pleiotropic effects. In this hypothesis article, the current clinical evidence on pioglitazone pharmacogenomics is summarized and related to variability in pioglitazone response. How genetic variation in the human genome affects the pharmacokinetics and pharmacodynamics of pioglitazone was examined. For pharmacodynamic effects, hypoglycemic and anti-atherosclerotic effects, risks of fracture or edema, and the increase in body mass index in response to pioglitazone based on genotype were examined. The genes CYP2C8 and PPARG are the most extensively studied to date and selected polymorphisms contribute to respective variability in pioglitazone pharmacokinetics and pharmacodynamics. We hypothesized that genetic variation in pioglitazone pathway genes contributes meaningfully to the clinically observed variability in drug response. To test the hypothesis that genetic variation in PPARG associates with variability in pioglitazone response, we conducted a meta-analysis to synthesize the currently available data on the PPARG p.Pro12Ala polymorphism. The results showed that PPARG 12Ala carriers had a more favorable change in fasting blood glucose from baseline as compared to patients with the wild-type Pro12Pro genotype (p=0.018. Unfortunately, findings for many other genes lack replication in independent cohorts to confirm association; further studies are needed. Also, the biological functionality of these polymorphisms is unknown. Based on current evidence, we propose that pharmacogenomics may provide an important tool to individualize pioglitazone therapy and better optimize therapy in patients with T2DM or other conditions for which pioglitazone

  17. Administration of pioglitazone alone or with alogliptin delays diabetes onset in UCD-T2DM rats.

    Science.gov (United States)

    Cummings, Bethany P; Bettaieb, Ahmed; Graham, James L; Stanhope, Kimber; Haj, Fawaz G; Havel, Peter J

    2014-04-01

    There is a need to identify strategies for type 2 diabetes prevention. Therefore, we investigated the efficacy of pioglitazone and alogliptin alone and in combination to prevent type 2 diabetes onset in UCD-T2DM rats, a model of polygenic obese type 2 diabetes. At 2 months of age, rats were divided into four groups: control, alogliptin (20 mg/kg per day), pioglitazone (2.5 mg/kg per day), and alogliptin+pioglitazone. Non-fasting blood glucose was measured weekly to determine diabetes onset. Pioglitazone alone and in combination with alogliptin lead to a 5-month delay in diabetes onset despite promoting increased food intake and body weight (BW). Alogliptin alone did not delay diabetes onset or affect food intake or BW relative to controls. Fasting plasma glucose, insulin, and lipid concentrations were lower and adiponectin concentrations were threefold higher in groups treated with pioglitazone. All treatment groups demonstrated improvements in glucose tolerance and insulin secretion during an oral glucose tolerance test with an additive improvement observed with alogliptin+pioglitazone. Islet histology revealed an improvement of islet morphology in all treatment groups compared with control. Pioglitazone treatment also resulted in increased expression of markers of mitochondrial biogenesis in brown adipose tissue and white adipose tissue, with mild elevations observed in animals treated with alogliptin alone. Pioglitazone markedly delays the onset of type 2 diabetes in UCD-T2DM rats through improvements of glucose tolerance, insulin sensitivity, islet function, and markers of adipose mitochondrial biogenesis; however, addition of alogliptin at a dose of 20 mg/kg per day to pioglitazone treatment does not enhance the prevention/delay of diabetes onset.

  18. A randomized, double blind, placebo-controlled trial of pioglitazone in combination with riluzole in amyotrophic lateral sclerosis.

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    Luc Dupuis

    Full Text Available BACKGROUND: Pioglitazone, an oral anti-diabetic that stimulates the PPAR-gamma transcription factor, increased survival of mice with amyotrophic lateral sclerosis (ALS. METHODS/PRINCIPAL FINDINGS: We performed a phase II, double blind, multicentre, placebo controlled trial of pioglitazone in ALS patients under riluzole. 219 patients were randomly assigned to receive 45 mg/day of pioglitazone or placebo (one: one allocation ratio. The primary endpoint was survival. Secondary endpoints included incidence of non-invasive ventilation and tracheotomy, and slopes of ALS-FRS, slow vital capacity, and quality of life as assessed using EUROQoL EQ-5D. The study was conducted under a two-stage group sequential test, allowing to stop for futility or superiority after interim analysis. Shortly after interim analysis, 30 patients under pioglitazone and 24 patients under placebo had died. The trial was stopped for futility; the hazard ratio for primary endpoint was 1.21 (95% CI: 0.71-2.07, p = 0.48. Secondary endpoints were not modified by pioglitazone treatment. Pioglitazone was well tolerated. CONCLUSION/SIGNIFICANCE: Pioglitazone has no beneficial effects on the survival of ALS patients as add-on therapy to riluzole. TRIAL REGISTRATION: Clinicaltrials.gov NCT00690118.

  19. Effects of pioglitazone and fenofibrate co-administration on bone biomechanics and histomorphometry in ovariectomized rats.

    Science.gov (United States)

    Smith, Susan Y; Samadfam, Rana; Chouinard, Luc; Awori, Malaika; Bénardeau, Agnes; Bauss, Frieder; Guldberg, Robert E; Sebokova, Elena; Wright, Matthew B

    2015-11-01

    Pioglitazone, the peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist is an effective therapy for type 2 diabetes, but has been associated with increased risk for bone fracture. Preclinical studies suggest that PPAR-α agonists (e.g., fenofibrate) increase bone mineral density/content, although clinical data on bone effects of fibrates are lacking. We investigated the effects of pioglitazone (10 mg/kg/day) and fenofibrate (25 mg/kg/day) on bone strength and bone histomorphometric parameters in osteopenic ovariectomized (OVX) rats. An additional group of rats received a combination of pioglitazone + fenofibrate to mimic the effects of a dual PPAR-α/γ agonist. The study consisted of a 13-week treatment phase followed by a 6-week treatment-free recovery period. Pioglitazone significantly reduced biomechanical strength at the lumbar spine and femoral neck compared with rats administered fenofibrate. Co-treatment with pioglitazone + fenofibrate had no significant effect on bone strength in comparison with OVX vehicle controls. Histomorphometric analysis of the proximal tibia revealed that pioglitazone suppressed bone formation and increased bone resorption at both cancellous and cortical bone sites relative to OVX vehicle controls. In contrast, fenofibrate did not affect bone resorption and only slightly suppressed bone formation. Discontinuation of pioglitazone treatment, both in the monotherapy and in the combination therapy arms, resulted in restoration of bone formation and resorption rates, demonstrating reversibility of effects. The above data support the concept that dual activation of PPAR-γ and PPAR-α attenuates the negative effects of PPAR-γ agonism on bone strength.

  20. Association of pioglitazone treatment with decreased bone mineral density in obese premenopausal patients with polycystic ovary syndrome: a randomized, placebo-controlled trial

    DEFF Research Database (Denmark)

    Glintborg, D.; Andersen, Mikael; Hagen, C.;

    2008-01-01

    .948-1.341) g/cm(2) (average decline 1.1%) and femoral neck 0.966 (0.767-1.217) vs. 0.952 (0.760-1.192) g/cm(2) (average decline 1.4%), both P ..., sex hormones, and body composition. CONCLUSION: Pioglitazone treatment was followed by decreased lumbar and hip BMD and decreased measures of bone turnover in a premenopausal study population relatively protected from bone mineral loss Udgivelsesdato: 2008/5...

  1. Efficacy and tolerability of pioglitazone in patients with type 2 diabetes mellitus: comparison with other oral antihyperglycaemic agents.

    Science.gov (United States)

    Derosa, Giuseppe

    2010-10-22

    Diabetes mellitus is a debilitating disease that is estimated to affect 366 million people by the year 2030. Type 2 diabetes mellitus (T2DM) is characterized by a progressive decline in pancreatic β-cell function and increased insulin resistance, and accounts for approximately 90% of people with diabetes. Oral antihyperglycaemic agents are extensively used in the treatment of T2DM. Thiazolidinediones are insulin sensitizers developed specifically for T2DM, which act via activation of peroxisome proliferator-activated receptors (PPARs). Pioglitazone is a thiazolidinedione that displays high affinity for PPARγ(1) and PPARγ(2), which are predominately expressed in adipose tissue. This review examines the published literature comparing the efficacy and tolerability of pioglitazone with other oral antihyperglycaemic agents in the treatment of patients with T2DM. Glycosylated haemoglobin, fasting glucose, insulin parameters and β-cell function are all improved with pioglitazone treatment, with efficacy similar to third-generation sulfonylureas, metformin and dipeptidyl peptidase-4 inhibitors. Pioglitazone reduces vascular risk and inflammatory markers, and improves carotid intima media thickness independent of its glycaemic effect. When compared with rosiglitazone, pioglitazone is associated with a reduction in the risk of hospitalization for acute myocardial infarction. Blood pressure is reduced and lipid profiles are favourably improved with pioglitazone; however, an increased risk for the development/exacerbation of heart failure, which is related to the increased incidence of oedema due to fluid retention, and fractures remain a concern. A low incidence of hypoglycaemia is observed with pioglitazone, especially compared with sulfonylureas. In conclusion, pioglitazone is an effective oral antihyperglycaemic agent with additional cardiovascular and lipid benefits that allows for the successful management of patients with T2DM.

  2. The neuroprotective benefit from pioglitazone (PIO) addition on the alpha lipoic acid (ALA)-based treatment in experimental diabetic rats.

    Science.gov (United States)

    Jin, Heung Yong; Lee, Kyung Ae; Wu, Jin Zu; Baek, Hong Sun; Park, Tae Sun

    2014-12-01

    In this study, we investigated the combined effect of pioglitazone (PIO) with alpha lipoic acid (ALA) on the peripheral nerves of diabetic rats. Animals were divided into 8 groups (N = 6-8) and designated according to ALA (100 mg/kg/day) and PIO (10 mg/kg/day) treatment: Normal, Normal + ALA, Normal + PIO, Normal + ALA + PIO, DM, DM + ALA, DM + PIO, and DM + ALA + PIO. After 24 weeks, current perception threshold, mechanical allodynia, oxidative stresses, intraepidermal nerve fiber density (IENFD), and axonal morphology in the sciatic nerve were compared among groups. IENFD in the DM + ALA + PIO group was significantly less reduced than in other DM groups (7.61 ± 0.52 vs. 5.62 ± 0.96, 5.56 ± 0.60, and 7.10 ± 0.70 for DM, DM + ALA, and DM + PIO, respectively P diabetes. Moreover, PIO can be preferentially considered when additional glucose-lowering agent is required in DPN patients treated with ALA.

  3. Protective Effects of Vildagliptin against Pioglitazone-Induced Bone Loss in Type 2 Diabetic Rats

    Science.gov (United States)

    Kwak, Kyung Min; Kim, Ju-Young; Yu, Seung Hee; Lee, Sihoon; Kim, Yeun Sun; Park, Ie Byung; Kim, Kwang-Won; Lee, Kiyoung

    2016-01-01

    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. We randomly divided 12-week-old male Zucker Diabetic Fatty (ZDF) rats into four groups; control, vildagliptin, pioglitazone, and vildagliptin and pioglitazone combination. Animals in each group received the respective treatments for 5 weeks. We performed an intraperitoneal glucose tolerance test (IPGTT) before and after treatment. BMD and the trabecular micro-architecture were measured by DEXA and micro CT, respectively, at the end of the treatment. The circulating levels of active GLP-1, bone turnover markers, and sclerostin were assayed. Vildagliptin treatment significantly increased BMD and trabecular bone volume. The combination therapy restored BMD, trabecular bone volume, and trabecular bone thickness that were decreased by pioglitazone. The levels of the bone formation marker, osteocalcin, decreased and that of the bone resorption marker, tartrate-resistant acid phosphatase (TRAP) 5b increased in the pioglitazone group. These biomarkers were ameliorated and the pioglitazone-induced increase in sclerostin level was lowered to control values by the addition of vildagliptin. In conclusion, our results indicate that orally administered vildagliptin demonstrated a protective effect on pioglitazone-induced bone loss in a type 2 diabetic rat model. PMID:27997588

  4. Effects of bed-time insulin versus pioglitazone on abdominal fat accumulation, inflammation and gene expression in adipose tissue in patients with type 2 diabetes.

    Science.gov (United States)

    Hartemann-Heurtier, Agnès; Halbron, Marine; Golmard, Jean-Louis; Jacqueminet, Sophie; Bastard, Jean-Philippe; Rouault, Christine; Ayed, Amine; Pieroni, Laurence; Clément, Karine; Grimaldi, André

    2009-10-01

    Intra-abdominal fat (IAF) and inflammatory markers are correlated with cardio-vascular risk. We compared the impact of bed-time insulin versus pioglitazone treatment on these parameters in type 2 diabetic (T2D) patients. Twenty-eight T2D patients poorly controlled with metformin and sulfonylurea were randomized to receive add-on therapy with pioglitazone or bed-time NPH insulin. IAF and subcutaneous fat (SCF) content, systemic low-grade inflammation level and expression of inflammation related genes in SCF, were measured before and after 24 weeks of treatment. Insulin and pioglitazone resulted in a significant decrease in HbA1c (-1.6% and -1.2%, respectively) and a significant increase in total body fat mass (1+/-2.3 and 3.3+/-2.7 kg, respectively). There was no change in IAF content after both treatments whereas significant increase in SCF content was only seen after pioglitazone treatment (pinsulin). hsCRP level decreased after pioglitazone and ferritin level decreased after insulin treatment. No change in mRNA expression of inflammation related genes was found after either treatment. This suggests that a 24-week treatment with pioglitazone or bed-time insulin has a similar impact on intra-abdominal fat mass and systemic low-grade inflammation.

  5. Effect of raw Radix Rehmanniae on the pharmacokinetics of pioglitazone in rats.

    Science.gov (United States)

    Shi, Zhan; Gao, Jingwen; Yuan, Yuemei; Zhu, Shuzhen; Yao, Meicun

    2014-05-01

    Raw Radix Rehmanniae (RRR) is a frequently used traditional Chinese medicine in the treatment of diabetes mellitus according to the statistics on all of the anti-diabetic formulas recorded in New National Traditional Chinese Medicine. Pioglitazone and RRR may be co-administrated for presumably enhanced therapeutic effects because of the common indications. Therefore, the aim of the study was to evaluate the effect of RRR on the pharmacokinetics of pioglitazone in healthy rats and type 2 diabetic rats. The pharmacokinetic effect of RRR on pioglitazone was studied in healthy rats and type 2 diabetic rats. A validated UPLC-MS/MS method was used to analyze the concentration of pioglitazone in blood samples. The pharmacokinetic parameters were calculated using non-compartmental analyses by Winnonlin 5.0.1. In healthy group, the pre-treatment of RRR significantly (Ppioglitazone; whereas in T2DM group, significant increase of C(max) and decrease of V/F and T½ were found after the rats were pre-treated with RRR. However, AUC(0-t) and CL/F remained unchanged in both healthy group and T2DM group. In conclusion, co-administration with RRR could alter the pharmacokinetic profiles of pioglitazone to statistically significant levels.

  6. Pentoxifylline and melatonin in combination with pioglitazone ameliorate experimental non-alcoholic fatty liver disease.

    Science.gov (United States)

    Zaitone, Sawsan; Hassan, Neven; El-Orabi, Naglaa; El-Awady, El-Sayed

    2011-07-15

    Insulin resistance, oxidative stress and cytokine imbalance are key pathophysiological mechanisms in non-alcoholic fatty liver disease (NAFLD). This study aimed at evaluating the effect of treatment with the insulin sensitizer, pioglitazone, the tumor necrosis factor-α inhibitor, pentoxifylline, and the antioxidant, melatonin and their combinations in rats with NAFLD. Rats were fed a high-fat diet (HFD) for eight weeks to induce NAFLD. For an additional eight weeks, rats were fed the HFD along with pioglitazone, pentoxifylline, melatonin alone or in combination. Liver index and insulin resistance index were calculated. Serum liver enzyme activities, total cholesterol, triglycerides and tumor necrosis factor-α (TNF-α) were determined. Tissue triglycerides, malondialdehyde and reduced glutathione were measured and liver injury was evaluated by histopathological examination. HFD induced severe hepatic steatosis, inflammation and fibrosis. In addition, liver index, insulin resistance index, activities of liver enzymes and serum level of total cholesterol, triglycerides and TNF-α were elevated. This was coupled with an increase in tissue triglycerides, malondialdehyde and depletion of reduced glutathione. Pioglitazone, pentoxifylline and melatonin, alone or in combination; reduced the insulin resistance index, activities of liver enzymes, hepatic malondialdehyde and increased hepatic reduced glutathione level. Pentoxifylline led to a decrease in serum TNF-α level, however, pioglitazone and melatonin reduced serum total cholesterol and triglycerides. In conclusion, data in this study indicate that pentoxifylline and melatonin can be used as promising adjuvant therapies to pioglitazone in the clinical management of NAFLD.

  7. Cardioprotective effect of pioglitazone in diabetic and non-diabetic rats subjected to acute myocardial infarction involves suppression of AGE-RAGE axis and inhibition of apoptosis.

    Science.gov (United States)

    Khodeer, Dina M; Zaitone, Sawsan A; Farag, Noha E; Moustafa, Yasser M

    2016-05-01

    Insulin resistance increases risk of cardiovascular diseases. This work investigated the protective effect of pioglitazone on myocardial infarction (MI) in non-diabetic and diabetic rats, focusing on its role on advanced glycated endproducts (AGEs) and cardiac apoptotic machinery. Male rats were divided into 2 experiments: experiment I and II (non-diabetic and diabetic rats) were assigned as saline, MI (isoproterenol, 85 mg/kg, daily), and MI+pioglitazone (5, 10, and 20 mg/kg). Injection of isoproterenol in diabetic rats produced greater ECG disturbances compared to non-diabetic rats. Treatment with pioglitazone (5 mg/kg) reduced the infarct size and improved some ECG findings. Pioglitazone (10 mg/kg) enhanced ECG findings, improved the histopathological picture and downregulated apoptosis in cardiac tissues. Whereas the higher dose of pioglitazone (20 mg/kg) did not improve most of the measured parameters but rather worsened some of them, such as proapoptotic markers. Importantly, a positive correlation was found between serum AGEs and cardiac AGE receptors (RAGEs) versus caspase 3 expression in the two experiments. Therefore, the current effect of pioglitazone was, at least in part, mediated through downregulation of AGE-RAGE axis and inhibition of apoptosis. Consequently, these data suggest that pioglitazone, at optimized doses, may have utility in protection from acute MI.

  8. Pioglitazone protects against cisplatin induced nephrotoxicity in rats and potentiates its anticancer activity against human renal adenocarcinoma cell lines.

    Science.gov (United States)

    Mahmoud, Mona F; El Shazly, Shimaa M

    2013-01-01

    Cisplatin-induced nephrotoxicity is a serious problem that limits its use in cancer treatment. The present study aimed to investigate the renal protective capacity of pioglitazone to reduce the cisplatin- induced nephrotoxicity. The underlying suggested mechanism(s) and whether this nephroprotective effect (if any) interferes with the cytotoxic effect of cisplatin on cancer cells were also investigated. Pioglitazone, Bisphenol A diglycidyl ether, BADGE, IP injected (Peroxisome proliferator- activated receptor gamma (PPAR-γ) antagonist), or their combination were administered to rats one hour before cisplatin injection. Moreover, their effects on the cell viability of human renal adenocarcinoma cell models (ACHN) were studied. The obtained results showed that pioglitazone improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-κB) genes expression in cisplatin injected rats. It increased both renal reduced glutathione (GSH) content and PPAR-γ gene expression. In contrast to the data obtained by prior administration of BADGE. Pioglitazone also potentiated the cytotoxic effect of cisplatin on human renal adenocarcinoma cells and this effect was abolished by BADGE co administration. In conclusion, these results suggested that pioglitazone protected against cisplatin- induced nephrotoxicity through its interaction with PPAR-γ receptors and antioxidant effects. Furthermore, pioglitazone did not interfere but rather potentiated the cytotoxic effects of cisplatin on human renal adenocarcinoma cells.

  9. Health and economic outcomes for exenatide once weekly, insulin, and pioglitazone therapies in the treatment of type 2 diabetes: a simulation analysis

    Directory of Open Access Journals (Sweden)

    Gaebler JA

    2012-04-01

    Full Text Available Julia A Gaebler1, Gerardo Soto-Campos2, Peter Alperin2, Marc Cohen2, Amy Blickensderfer1, Matthew Wintle1, David Maggs1, Byron Hoogwerf3, Jenny Han1, Richard Pencek1, Barbara Peskin21Amylin Pharmaceuticals, Inc, San Diego CA, 2Archimedes Inc, San Francisco CA, 3Eli Lilly and Company, Indianapolis, IN, USABackground: Patients with type 2 diabetes (T2DM are at risk of long-term vascular complications. In trials, exenatide once weekly (ExQW, a GLP-1R agonist, improved glycemia, weight, blood pressure (BP, and lipids in patients with T2DM. We simulated potential effects of ExQW on vascular complications, survival, and medical costs over 20 years versus standard therapies.Patients and methods: The Archimedes model was used to assess outcomes for ~25,000 virtual patients with T2DM (NHANES 1999–2006 [metformin ± sulfonylureas, age 57 years, body mass index 33 kg/m2, weight 94 kg, duration T2DM 9 years, hemoglobin A1c [A1C] 8.1%]. The effects of three treatment strategies were modeled and compared to moderate-adherence insulin therapy: advancement to high-adherence insulin at A1C ≥ 8% (treat to target A1C < 7% and addition of pioglitazone (PIO or ExQW from simulation start. ExQW effects on A1C, weight, BP, and lipids were modeled from clinical trial data. Costs, inflated to represent 2010 $US, were derived from Medicare data, Drugstore.com, and publications. As ExQW was investigational, we omitted ExQW, PIO, and insulin pharmacy costs.Results: By year 1, ExQW treatment decreased A1C (~1.5%, weight (~2 kg, and systolic BP (~5 mmHg. PIO and high-adherence insulin decreased A1C by ~1%, increased weight, and did not affect systolic BP. After 20 years, A1C was ~7% with all strategies. ExQW decreased rates of cardiovascular and microvascular complications more than PIO or high-adherence insulin versus moderate-adherence insulin. Over 20 years, ExQW treatment resulted in increased quality-adjusted life-years (QALYs of ~0.3 years/person and cost savings of

  10. Efficacy of Pioglitazone in Treatment of Steatohepatitis with Diabetes Mellitus%吡格列酮对糖尿病合并非酒精性脂肪肝炎的疗效观察

    Institute of Scientific and Technical Information of China (English)

    徐园园; 纪易斐

    2011-01-01

    Objective To observe the efficacy and adverse drug reactions of pioglitazone in treatment of non-alcoholic steatohepatitis (NASH) with type 2 diabetes mellitus. Methods Fifty five patients with NASH were randomly divided into two groups: pioglitazone group with pioglitazone 30 mg per day, while control group with Hypoglycemic drug except for thiazolidine dione and Biguanides, the period of treatment was 24 weeks. Fasting blood glucose,2-hour postprandial blood glucose, fasting blood insulin,glycosylated hemoglobin,insulin resistance index,alanine aminotransferase,aspartate aminotransferase blood lipid and the degree of fatty liver were measured before and after the treatment. Results Both the two groups significantly reduced fasting blood glucose,2-hour postprandial blood glucose,glycosylated hemoglobin after treatment,but there were not significant differences in two groups( P > 0.05 ). Compared with the patients in control group, Pioglitazone group had significant differences in lower fasting blood insulin and insulin resistance index,improvement liver function and blood lipid,modification the degree of fatty liver( P <0.05 ). Conclusion Pioglitazone can increase insulin sensitivity, improve the abnormalities of enzyme tests, reduce insulin resistante and improve the fatty liver.%目的 临床观察胰岛素增敏剂吡格列酮对2型糖尿病合并非酒精性脂肪肝炎患者治疗的有效性和安全性.方法 将55例2型糖尿病合并非酒精性脂肪肝炎患者随机分为两组,吡格列酮组给予吡格列酮30 mg,1次/d,对照组给予除噻唑烷二酮类以外的其他降糖药物治疗,疗程均为24周.比较两组治疗前后指标:空腹血糖、餐后2 h血糖、空腹胰岛素、糖化血红蛋白、胰岛素抵抗指数、天冬氨酸转氨酶、丙氨酸转氨酶、血脂及脂肪肝程度.结果 治疗后两组空腹血糖、餐后2 h血糖、糖化血红蛋白均有明显改善,两组比较差异无统计学意义(P>0.05),吡格

  11. A Metabolic Inhibitory Cocktail for Grave Cancers: Metformin, Pioglitazone and Lithium Combination in Treatment of Pancreatic Cancer and Glioblastoma Multiforme.

    Science.gov (United States)

    Elmaci, İlhan; Altinoz, Meric A

    2016-10-01

    Pancreatic cancer (PC) and glioblastoma multiforme (GBM) are among the human cancers with worst prognosis which require an urgent need for efficient therapies. Here, we propose to apply to treat both malignancies with a triple combination of drugs, which are already in use for different indications. Recent studies demonstrated a considerable link between risk of PC and diabetes. In experimental models, anti-diabetogenic agents suppress growth of PC, including metformin (M), pioglitazone (P) and lithium (L). L is used in psychiatric practice, yet also bears anti-diabetic potential and selectively inhibits glycogen synthase kinase-3 beta (GSK-3β). M, a biguanide class anti-diabetic agent shows anticancer activity via activating AMP-activated protein kinase (AMPK). Glitazones bind to PPAR-γ and inhibit NF-κB, triggering cell proliferation, apoptosis resistance and synthesis of inflammatory cytokines in cancer cells. Inhibition of inflammatory cytokines could simultaneously decrease tumor growth and alleviate cancer cachexia, having a major role in PC mortality. Furthermore, mutual synergistic interactions exist between PPAR-γ and GSK-3β, between AMPK and GSK-3β and between AMPK and PPAR-γ. In GBM, M blocks angiogenesis and migration in experimental models. Very noteworthy, among GBM patients with type 2 diabetes, usage of M significantly correlates with better survival while reverse is true for sulfonylureas. In experimental models, P synergies with ligands of RAR, RXR and statins in reducing growth of GBM. Further, usage of P was found to be lesser in anaplastic astrocytoma and GBM patients, indicating a protective effect of P against high-grade gliomas. L is accumulated in GBM cells faster and higher than in neuroblastoma cells, and its levels further increase with chronic exposure. Recent studies revealed anti-invasive potential of L in GBM cell lines. Here, we propose that a triple-agent regime including drugs already in clinical usage may provide a

  12. Pioglitazone in adult rats reverses immediate postnatal overfeeding-induced metabolic, hormonal, and inflammatory alterations.

    Science.gov (United States)

    Boullu-Ciocca, S; Tassistro, V; Dutour, A; Grino, M

    2015-12-01

    Immediate postnatal overfeeding in rats, obtained by reducing the litter size, results in early-onset obesity. Such experimental paradigm programs overweight, insulin resistance, dyslipidemia, increased adipose glucocorticoid metabolism [up-regulation of glucocorticoid receptor (GR) and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)], and overexpression of proinflammatory cytokines in mesenteric adipose tissue (MAT) in adulthood. We studied the effects of pioglitazone, a PPARγ agonist, treatment on the above-mentioned overfeeding-induced alterations. Nine-month-old rats normofed or overfed during the immediate postnatal period were given pioglitazone (3 mg/kg/day) for 6 weeks. Pioglitazone stimulated weight gain and induced a redistribution of adipose tissue toward epididymal location with enhanced plasma adiponectin. Treatment normalized postnatal overfeeding-induced metabolic alterations (increased fasting insulinemia and free fatty acids) and mesenteric overexpression of GR, 11β-HSD11, CD 68, and proinflammatory cytokines mRNAs, including plasminogen-activator inhibitor type 1. Mesenteric GR mRNA levels correlated positively with mesenteric proinflammatory cytokines mRNA concentrations. In vitro incubation of MAT obtained from overfed rats demonstrated that pioglitazone induced a down-regulation of GR gene expression and normalized glucocorticoid-induced stimulation of 11β-HSD1 and plasminogen-activator inhibitor type 1 mRNAs. Our data show for the first time that the metabolic, endocrine, and inflammatory alterations induced by early-onset postnatal obesity can be reversed by pioglitazone at the adulthood. They demonstrate that pioglitazone, in addition to its well-established effect on adipose tissue redistribution and adiponectin secretion, reverses programing-induced adipose GR, 11β-HSD1, and proinflammatory cytokines overexpression, possibly through a GR-dependent mechanism.

  13. A pilot double-blind placebo-controlled trial of pioglitazone as adjunctive treatment to risperidone: Effects on aberrant behavior in children with autism.

    Science.gov (United States)

    Ghaleiha, Ali; Rasa, Soudeh Mohebbi; Nikoo, Mohammadali; Farokhnia, Mehdi; Mohammadi, Mohammad-Reza; Akhondzadeh, Shahin

    2015-09-30

    To assess the safety and efficacy of pioglitazone added to risperidone in the treatment of irritability in autistic disorder (AD), we conducted this study. In a 10-week, randomized, double-blind, parallel-group, placebo-controlled clinical trial, 44 outpatients of both genders aged 4-12 years with a diagnosis of AD and a score of ≥12 on the Aberrant Behavior Checklist-Community (ABC-C) irritability subscale were included. Mean change of ABC-C irritability subscale score as primary outcome, change in other ABC-C subscale scores and partial and complete responses were compared between two groups. Twenty patients completed the trial in each group. Level of reduction and effect of time×treatment interaction in the treatment group were significant for irritability (P=0.03), lethargy/social withdrawal (P=0.04) and hyperactivity/non-compliance (P=0.03) but not for stereotypic behavior and inappropriate speech subscales compared with the placebo group. Vomiting and headache were the most frequent reported side-effects. Results of this preliminary study indicate positive effects of pioglitazone compared with placebo in improving the behavioral symptoms of AD.

  14. The impact of pioglitazone on bladder cancer and cardiovascular events.

    Science.gov (United States)

    Lee, Esther J; Marcy, Todd R

    2014-08-01

    Type 2 diabetes mellitus (T2DM) is a chronic condition with increasing prevalence and severe complications. Thiazolidinediones have been marketed since 1997 and are effective glucose-lowering drugs, but individual drugs within the class have been linked to serious adverse effects that resulted in the removal of troglitazone from the market, restrictions to rosiglitazone's use, and a warning added to pioglitazone's label. In 2007, a meta-analysis linked rosiglitazone to myocardial infarction (MI). Pioglitazone does not appear to share this risk. To the contrary, pioglitazone may reduce risk for MI. However, retrospective evaluations have increasingly linked pioglitazone to a higher risk of bladder cancer that appears to be time- and dose-dependent. Pioglitazone remains a medication appropriate for consideration in the management of T2DM; however, clinicians and patients should weigh its risks compared with alternatives, with a regular review of risks.

  15. Polymorphism of peroxisome proliferator-activated receptor γ (PPARγ) Pro12Ala in the Iranian population: relation with insulin resistance and response to treatment with pioglitazone in type 2 diabetes.

    Science.gov (United States)

    Namvaran, Fatemeh; Azarpira, Negar; Rahimi-Moghaddam, Parvaneh; Dabbaghmanesh, Mohammad Hossein

    2011-12-05

    The peroxisome proliferator-activated receptor γ (PPARγ) has important effects on insulin sensitivity, obesity and diabetes. Pioglitazone improves insulin sensitivity by activating PPARγ. In view of inter-individual variability in therapeutic response to pioglitazone, this study was designed to search for an association between type 2 diabetes mellitus and Pro12Ala single-nucleotide polymorphism (SNP) in PPARγ (SNP rs1801282) and to investigate whether these genetic variants affect pioglitazone response in an Iranian population. A total of 101 patients with type 2 diabetes were treated for 12 weeks with pioglitazone (15 mg/day). Paraclinical parameters were measured before and after therapy. We genotyped 128 control participants without diabetes and all patients with type 2 diabetes. The Pro12Ala polymorphism in PPARγ was detected with real-time PCR. The Ala allele was found in 7% of the control participants vs. 3% of those with type 2 diabetes (P=0.04). The genotypic frequencies of Pro/Ala were 14.06% in the former group vs. 5.94% in the latter (P=0.036). There were significant changes in some laboratory values and biochemical markers of insulin sensitivity after pioglitazone therapy. The Pro12Ala polymorphism was associated with significant changes in insulin-to-glucose ratio after treatment (P=0.015 and P=0.005). Our findings suggest that in carriers of the 12Ala variant, pioglitazone significantly reduced the risk of type 2 diabetes, and in diabetic patients with the Pro12Ala genotype, the therapeutic response to treatment was better than in patients with the Pro12Pro genotype, although the difference between groups did not reach statistical significance. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Additive Renoprotection by Pioglitazone and Fenofibrate against Inflammatory, Oxidative and Apoptotic Manifestations of Cisplatin Nephrotoxicity: Modulation by PPARs.

    Science.gov (United States)

    Helmy, Mai M; Helmy, Maged W; El-Mas, Mahmoud M

    2015-01-01

    Nephrotoxicity is a major side effect for the antineoplastic drug cisplatin. Here, we employed pharmacological, biochemical, and molecular studies to investigate the role of peroxisome proliferator-activated receptors (PPARs) in cisplatin nephrotoxicity. Rats were treated with a single i.p. dose of cisplatin (5 mg/kg) alone or combined with pioglitazone (PPARγ agonist), fenofibrate (PPARα agonist), pioglitazone plus fenofibrate, or thalidomide (Tumor necrosis factor-α inhibitor; TNF-α). Cisplatin nephrotoxicity was evidenced by rises in renal indices of functional (blood urea nitrogen, BUN, and creatinine), inflammatory (TNF-α, interleukin 6, IL-6), oxidative (increased malondialdehyde, MDA, and decreased superoxide dismutase, SOD and nitric oxide metabolites, NOx), apoptotic (caspase 3), and histological (glomerular atrophy, acute tubular necrosis and vacuolation) profiles. Cisplatin effects were partly abolished upon concurrent exposure to pioglitazone, fenofibrate, or thalidomide; more renoprotection was observed in rats treated with pioglitazaone plus fenofibrate. Immunostaining showed that renal expressions of PPARα and PPARγ were reduced by cisplatin and restored to vehicle-treated values after simultaneous treatment with pioglitazone or fenofibrate. Fenofibrate or pioglitazone renoprotection remained unaltered after concurrent blockade of PPARα (GW6471) and PPARγ (GW9662), respectively. To complement the rat studies, we also report that in human embryonic kidney cells (HEK293 cells), increases caused by cisplatin in inflammatory, apoptotic, and oxidative biomarkers were (i) partly improved after exposure to pioglitazone, fenofibrate, or thalidomide, and (ii) completely disappeared in cells treated with a combination of all three drugs. These data establish that the combined use of pioglitazone and fenofibrate additively improved manifestations of cisplatin nephrotoxicity through perhaps GW6471/GW9662-insensitive mechanisms.

  17. Pioglitazone:A review of analytical methods

    Institute of Scientific and Technical Information of China (English)

    N. Satheeshkumar; S. Shantikumar; R. Srinivas

    2014-01-01

    Pioglitazone is an oral anti-hyperglycemic agent. It is used for the treatment of diabetes mellitus type 2. It selectively stimulates nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-gamma). It was the tenth-best-selling drug in the U.S. in 2008. This article examines published analytical methods reported so far in the literature for the determination of pioglitazone in biological samples and pharmaceutical formulations. They include various techniques like electrochemical methods, spectrophotometry, capillary electrophoresis, high-performance liquid chromatography, liquid chromatography-electrospray ionization-tandem mass spectrometry and high-performance thin layer chromatography.

  18. Suppressive effect of pioglitazone, a PPAR gamma ligand, on azoxymethane-induced colon aberrant crypt foci in KK-Ay mice.

    Science.gov (United States)

    Ueno, Toshiya; Teraoka, Naoya; Takasu, Shinji; Nakano, Katsuya; Takahashi, Mami; Yamamoto, Masafumi; Fujii, Gen; Komiya, Masami; Yanaka, Akinori; Wakabayashi, Keiji; Mutoh, Michihiro

    2012-01-01

    Obesity is an established risk factor for colorectal cancer. Pioglitazone is a peroxisome proliferator- activated receptor γ(PPARγ) agonist that induces differentiation in adipocytes and induces growth arrest and/or apoptosis in vitro in several cancer cell lines. In the present study, we investigated the effect of pioglitazone on the development of azoxymethane-induced colon aberrant crypt foci (ACF) in KK-Ay obesity and diabetes model mice, and tried to clarify mechanisms by which the PPARγ ligand inhibits ACF development. Administration of 800 ppm pioglitazone reduced the number of colon ACF / mouse to 30% of those in untreated mice and improved hypertrophic changes of adipocytes in KK-Ay mice with significant reduction of serum triglyceride and insulin levels. Moreover, mRNA levels of adipocytokines, such as leptin, monocyte chemoattractant protein-1 and plasminogen activator inhibitor-1, in the visceral fat were decreased. PCNA immunohistochemistry revealed that pioglitazone treatment suppressed cell proliferation in the colorectal epithelium with elevation of p27 and p53 gene expression. These results suggest that pioglitazone prevented obesity-associated colon carcinogenesis through improvement of dysregulated adipocytokine levels and high serum levels of triglyceride and insulin, and increase of p27 and p53 mRNA levels in the colorectal mucosa. These data indicate that pioglitazone warrants attention as a potential chemopreventive agent against obesity-associated colorectal cancer.

  19. Effects of intensive insulin therapy alone and in combination with pioglitazone on body weight, composition, distribution and liver fat content in patients with type 2 diabetes.

    Science.gov (United States)

    Shah, P K; Mudaliar, S; Chang, A R; Aroda, V; Andre, M; Burke, P; Henry, R R

    2011-06-01

    To evaluate the effects of intensive insulin therapy alone and with added pioglitazone on body weight, fat distribution, lean body mass (LBM) and liver fat in type 2 diabetic patients. Twenty-five insulin-treated, obese patients with type 2 diabetes were randomized to addition of pioglitazone 45 mg (n = 12) or placebo (n = 13) and treated intensively for 12-16 weeks. Dual-energy X-ray absorptiometry/abdominal computed tomography scans were performed before/after treatment. LBM, visceral/subcutaneous adipose tissue (VAT/SAT) and liver/spleen (L/S) attenuation ratios were measured pre-/posttreatment (a ratio insulin alone and insulin + pioglitazone significantly improved glycaemic control (7.8 ± 0.3 to 7.2 ± 0.3% and 7.6 ± 0.3 to 7.1 ± 0.4%, respectively). Body weight gain was greater with insulin + pioglitazone (4.9 ± 4.5 kg) versus insulin therapy alone (1.7 ± 0.7 kg). SAT increased significantly with pioglitazone + insulin therapy (393.9 ± 48.5 to 443.2 ± 56.7 cm(2) , p insulin therapy alone (412.9 ± 42.5 to 420.8 ± 43.8 cm(2) ). VAT decreased non-significantly in both groups (240.3 ± 41.7 to 223.8 ± 38.1 cm(2) with insulin + pioglitazone and 266.6 ± 27.4 to 250.5 ± 22.2 cm(2) with insulin therapy). LBM increased significantly by 1.92 ± 0.74 kg with insulin + pioglitazone treatment. The L/S attenuation ratio in the placebo + insulin group decreased from 1.08 ± 0.1 to 1.04 ± 0.1 (p = ns) and increased from 1.00 ± 0.1 to 1.08 ± 0.05 (p = 0.06) in the pioglitazone + insulin group. Intensification of insulin therapy in type 2 diabetic patients causes modest weight gain and no change in body fat distribution, LBM or liver fat. In contrast, the addition of pioglitazone, at equivalent glycaemia, increases weight gain, fat mass and SAT; increases LBM and tends to decrease liver fat. These changes in fat distribution may contribute to the beneficial effects of pioglitazone, despite greater weight gain. Published 2011. This article is a US Government work

  20. Combination of Vildagliptin and Pioglitazone in Experimental Type 2 Diabetes in Male Rats.

    Science.gov (United States)

    Refaat, Rowaida; Sakr, Ahmed; Salama, Mona; El Sarha, Ashgan

    2016-09-01

    Preclinical Research The majority of studies on vildagliptin and pioglitazone have focused on their combination in glycemic control. The aim of the present study was to investigate their effects in combination on (i) hyperglycemia-induced oxidative stress and inflammation and (ii) on organs involved in the pathophysiology of diabetes, pancreas, kidney and liver. Type 2 diabetes was induced using low-dose streptozotocin in male Wistar rats. Diabetic rats were treated for 4 weeks, with vildagliptin (10 mg/kg/day), pioglitazone (10 mg/kg/day) and their combination. Diabetic rats showed elevated fasting serum glucose, fasting serum insulin, serum transaminases together with a deleterious lipid profile and elevated serum creatinine and urea concentrations. Serum levels of the inflammatory markers tumor necrosis factor-α (TNF-α) and nitrite/nitrate were also elevated compared to normal rats. Oxidative stress was manifested by lowered hepatic reduced glutathione (GSH) and increased malondialdehyde (MDA) levels. Pancreatic sections from diabetic rats showed degenerated islets with poorly maintained architecture that was prevented by drug treatment. Pioglitazone was generally more effective than vildagliptin in the studied parameters except for the lipid profile where the effect of both drugs was comparable and for the liver enzymes and renal parameters where vildagliptin was more effective. The combination of vildagliptin and pioglitazone produced superior effects than either drug alone. Drug Dev Res 77 : 251-257, 2016. © 2016 Wiley Periodicals, Inc.

  1. The peroxisome proliferator-activated receptor-γ agonist pioglitazone protects against cisplatin-induced renal damage in mice.

    Science.gov (United States)

    Jesse, Cristiano R; Bortolatto, Cristiani F; Wilhelm, Ethel A; Roman, Silvane Souza; Prigol, Marina; Nogueira, Cristina W

    2014-01-01

    Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists not only improve metabolic abnormalities of diabetes and consequent diabetic nephropathy, but they also protect against non-diabetic kidney disease in experimental models. Here, we investigated the effect of PPAR-γ agonist pioglitazone against acute renal injury on a cisplatin model in mice. Nephrotoxicity was induced by a single intraperitoneal (i.p.) injection of cisplatin (10 mg kg(-1)). Pioglitazone was administered for six consecutive days in doses of 15 or 30 mg kg(-1)  day(-1), per os (p.o.), starting 3 days before cisplatin injection. Cisplatin treatment to mice induced a marked renal failure, characterized by a significant increase in serum urea and creatinine levels and alterations in renal tissue architecture. Cisplatin exposure induced oxidative stress as indicated by decreased levels of non-enzymatic antioxidant defenses [glutathione (GSH) and ascorbic acid levels] and components of the enzymatic antioxidant defenses [superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx), glutathione reductase (GR) and and glutathione S-transferase(GST) activities)] in renal tissue. Administration of pioglitazone markedly protected against the increase in urea and creatinine levels and histological alterations in kidney induced by cisplatin treatment. Pioglitazone administration ameliorated GSH and ascorbic acid levels decreased by cisplatin exposure in mice. Pioglitazone protected against the inhibition of CAT, SOD, GPx, GR and GST activities induced by cisplatin in the kidneys of mice. These results indicated that pioglitazone has a protective effect against cisplatin-induced renal damage in mice. The protection is mediated by preventing the decline of antioxidant status. The results have implications in use of PPAR-γ agonists in human application for protecting against drugs-induced nephrotoxicity.

  2. Comparison of the Effects of Pioglitazone versus Placebo when Given in Addition to Standard Insulin Treatment in Patients with Type 2 Diabetes Mellitus Requiring Hemodialysis: Results from the PIOren Study

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    Jan Galle

    2012-05-01

    Full Text Available Background: Patients with type 2 diabetes mellitus and advanced kidney disease are usually treated with insulin. However, the prolonged pharmacokinetic insulin profile in patients with delayed renal insulin elimination impairs a successful therapy. Due to its hepatic metabolism, pioglitazone is a potential candidate for additional administration. The aim of this study was to investigate the effect of pioglitazone versus placebo on total daily insulin requirements and several pleiotropic factors in type 2 diabetes patients requiring hemodialysis. Methods: The effect of pioglitazone (30 mg versus placebo was explored in this prospective, randomized, double-blind parallel multicenter phase II study analyzing data from 36 patients with type 2 diabetes mellitus currently under hemodialysis (25 male, 11 female, aged 69.2 ± 7.9 years, baseline HbA1c 7.6 ± 0.9%. The most important efficacy parameters collected before dialysis and after an overnight fast at baseline and after 6 months were: total daily insulin dose, HbA1c, fasting blood glucose, adiponectin, HDL, LDL, triglycerides, NT-proBNP, and ultrafiltrate volume. Results: Application of pioglitazone resulted in a significant decrease of the daily insulin dose by 35% versus baseline (placebo: –10%, n.s., improvement in HbA1c (–0.60 ± 0.87%, p = 0.015; placebo: 0.21 ± 1.1%, n.s. and adiponectin (7.33 ± 4.80 mg/l, p Conclusions: Addition of pioglitazone to insulin in patients with late-stage kidney failure requiring hemodialysis is a well-tolerated treatment option that improves glycemic control with simultaneous insulin-sparing potential.

  3. Pioglitazone, a specific ligand of peroxisome proliferator-activated receptor-gamma, protects pancreas against acute cerulein-induced pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Peter C Konturek; Artur Dembinski; Zygmunt Warzecha; Grzegorz Burnat; Piotr Ceranowicz; Eckhart G Hahn; Marcin Dembinski; Romana Tomaszewska; Stanislaw J Konturek

    2005-01-01

    AIM: To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-γ (PPARγ)ligand, on the development of acute pancreatitis (AP) and on the expression of heat shock protein 70 (HSP70) in the pancreas.METHODS: AP was induced in rats by subcutaneous infusion of cerulein for 5 h. Pancreatic blood flow was measured by laser Doppler flowmetry. Plasma lipase activity, interleukin-1β (IL-1β) and IL-10 were determined.Pancreatic weight and histology were evaluated and pancreatic DNA synthesis and blood flow as well as pancreatic mRNA for IL-1β and HSP70 were assessed in rats treated with pioglitazone alone or in combination with cerulein.RESULTS: Pioglitazone administered (10-100 mg/kg I.g.)30 min before cerulein, attenuated dose-dependently the pancreatic tissue damage in cerulein-induced pancreatitis (CIP) as demonstrated by the improvement of pancreatic histology, reduction in plasma lipase activity,plasma concentration of pro-inflammatory IL-1β and its gene expression in the pancreas and attenuation of the pancreatitis-evoked fall in pancreatic blood flow. CIP increased pancreatic HSP70 mRNA and protein expression in the pancreas and this effect was enhanced by pioglitazone treatment.CONCLUSION: Pioglitazone attenuates CIP and the beneficial effect of this pioglitazone is multifactorial probably due to its anti-inflammatory activities, to the suppression of IL-1β and to the overexpression of HSP70.PPARγ ligands could represent a new therapeutic option in the treatment of AP.

  4. Pioglitazone, a specific ligand of peroxisome proliferator-activated receptor-gamma, protects pancreas against acute cerulein-induced pancreatitis

    Science.gov (United States)

    Konturek, Peter C; Dembinski, Artur; Warzecha, Zygmunt; Burnat, Grzegorz; Ceranowicz, Piotr; Hahn, Eckhart G; Dembinski, Marcin; Tomaszewska, Romana; Konturek, Stanislaw J

    2005-01-01

    AIM: To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-γ (PPARγ) ligand, on the development of acute pancreatitis (AP) and on the expression of heat shock protein 70 (HSP70) in the pancreas. METHODS: AP was induced in rats by subcutaneous infusion of cerulein for 5 h. Pancreatic blood flow was measured by laser Doppler flowmetry. Plasma lipase activity, interleukin-1β (IL-1β) and IL-10 were determined. Pancreatic weight and histology were evaluated and pancreatic DNA synthesis and blood flow as well as pancreatic mRNA for IL-1β and HSP70 were assessed in rats treated with pioglitazone alone or in combination with cerulein. RESULTS: Pioglitazone administered (10-100 mg/kg i.g.) 30 min before cerulein, attenuated dose-dependently the pancreatic tissue damage in cerulein-induced pancreatitis (CIP) as demonstrated by the improvement of pancreatic histology, reduction in plasma lipase activity, plasma concentration of pro-inflammatory IL-1β and its gene expression in the pancreas and attenuation of the pancreatitis-evoked fall in pancreatic blood flow. CIP increased pancreatic HSP70 mRNA and protein expression in the pancreas and this effect was enhanced by pioglitazone treatment. CONCLUSION: Pioglitazone attenuates CIP and the beneficial effect of this pioglitazone is multifactorial probably due to its anti-inflammatory activities, to the suppression of IL-1β and to the overexpression of HSP70. PPARγ ligands could represent a new therapeutic option in the treatment of AP. PMID:16419161

  5. Effects of pioglitazone and metformin on vascular endothelial function in patients with type 2 diabetes treated with sulfonylureas.

    Science.gov (United States)

    Naka, Katerina K; Papathanassiou, Katerina; Bechlioulis, Aris; Pappas, Konstantinos; Kazakos, Nikolaos; Kanioglou, Chryssanthi; Kostoula, Aggeliki; Vezyraki, Patra; Makriyiannis, Demetrios; Tsatsoulis, Agathocles; Michalis, Lampros K

    2012-01-01

    Pioglitazone and metformin are insulin sensitisers used for the treatment of T2DM. The effects of pioglitazone and metformin on endothelial function, assessed by FMD, in T2DM patients treated with sulfonylureas were compared. Patients were randomised to receive pioglitazone (n = 15) 30 mg once daily or metformin (n = 16) 850 mg twice daily for six months. Pioglitazone significantly decreased fasting insulin, HbA(1C) and HOMA-IR (p pioglitazone, compared with metformin, did not reach significance (p = 0.11). Treatment-induced changes in FMD were not associated with the effects of the two insulin sensitisers on glycaemic control or insulin resistance. The beneficial effects of pioglitazone and metformin on endothelial function in T2DM patients did not differ greatly. Larger studies are needed to explore whether a potentially greater benefit with pioglitazone may exist.

  6. Pioglitazone inhibits the expression of nicotinamide adenine dinucleotide phosphate oxidase and p38 mitogen-activated protein kinase in rat mesangial cells

    Institute of Scientific and Technical Information of China (English)

    WANG Shan; YE Shan-dong; SUN Wen-jia; HU Yuan-yuan

    2013-01-01

    Background Oxidative Stress and p38 mitogen-activated protein kinase (p38MAPK) play a vital role in renal fibrosis.Pioglitazone can protect kidney but the underlying mechanisms are less clear.The purpose of this study was to investigate the effect of pioglitazone on oxidative stress and whether the severity of oxidative stress was associated with the phosphorylation level of p38MAPK.Methods Rat mesangial cells were cultured and randomly assigned to control group,high glucose group and pioglitazone group.After 48-hour exposure,the supernatants and ceils were collected.The protein levels of p22phox,p47phox,phosphorylated p38MAPK,total p38MAPK were measured by Western blotting.The gene expressions of p22phox,p47phox were detected by RT-PCR.The levels of intracellular reactive oxygen species (ROS) were determined by flow cytometry.The levels of superoxide dismutase (SOD) and maleic dialdehyde (MDA) in the supernatant were determined respectively.Results Compared with the control group,the expression levels of p22phox,p47phox,phospho-p38 and ROS significantly increased,activity of SOD decreased in high glucose group,while the level of MDA greatly increased (P <0.01).Pioglitazone significantly suppressed p22phox,p47phox expressions and oxidative stress induced by high glucose.The expressions of p22phox,p47phox,phospho-p38MAPK and ROS generation were markedly reduced after pioglitazone treatment (P <0.05).The activity of SOD in the the supernatant increased (P <0.05),while the level of MDA decreased greatly by pioglitazone (P <0.05).The level of oxidative stress was associated with the phosphorylation level of p38MAPK (P <0.01).Conclusion Pioglitazone can inhibit oxidative stress through suppressing NADPH oxidase expression and p38MAPK phosphorylation.

  7. Pioglitazone ameliorates memory deficits in streptozotocin-induced diabetic mice by reducing brain β-amyloid through PPARY activation

    Institute of Scientific and Technical Information of China (English)

    Li-ping LIU; Tian-hua YAN; Li-ying JIANG; Wei HU; Meng HU; Chao WANG; Qian ZHANG

    2013-01-01

    Aim:To examine the effects of pioglitazone,a PPARY agonist,on memory performance and brain amyloidogenesis in streptozotocin (STZ)-induced diabetic mice.Methods:ICR male mice were injected with STZ (150 mg/kg,iv) to induce experimental diabetes.Pioglitazone (9 and 18 mg·kg1-d-1,po) was administered for 6 weeks.Passive avoidance and Morris water maze (MWM) tests were used to evaluate cognitive function.The blood glucose and serum insulin levels were detected using the glucose oxidase method and an ELISA assay,respectively.β-amyloid (Aβ),β-amyloid precursor protein (APP),β-amyloid precursor protein cleaving enzyme 1 (BACE1),NF-κB p65,the receptor for advanced glycation end products (RAGE) and PPARy in the brains were analyzed using Western blotting assays.Results:The STZ-induced diabetic mice characterized by hyperglycemia and hypoinsulinemia performed poorly in both the passive avoidance and MWM tests,accompanied by increased Aβ1-40/Aβ1-42,APP,BACE1,NF-κB p65 and RAGE levels and decreased PPARy level in the hippocampus and cortex.Chronic pioglitazone treatment significantly ameliorated the memory deficits of STZ-induced diabetic mice,and suppressed expression of APP,BACE1,RAGE and NF-κB p65,and activated PPARy in the hippocampus and cortex.However,pioglitazone did not significantly affect blood glucose and insulin levels.Conclusion:Pioglitazone ameliorates memory deficits in STZ-induced diabetic mice by reducing brain Aβ level via activation of PPARy,which is independent of its effects on blood glucose and insulin levels.The results suggest that pioglitazone may be used for treating the cognitive dysfunction in type 1 diabetes mellitus.

  8. Effect of pioglitazone versus insulin glargine on cardiac size, function, and measures of fluid retention in patients with type 2 diabetes

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    Groop Leif

    2009-03-01

    Full Text Available Abstract Background Both insulin and thiazolidinediones (TZDs are effective in the treatment of hyperglycaemia and amelioration of insulin resistance in type 2 diabetes but have side effects including weight gain and fluid retention. The use of TZDs has been further hampered by the risk of adverse cardiovascular events including heart failure. The present study evaluated the effect of pioglitazone or insulin glargine on cardiac function and size as well as on surrogate markers of fluid retention such as weight, haemoglobin and natriuretic peptides. Methods Thirty patients with inadequate glycaemic control on metformin and sulfonylurea were randomised to receive add-on therapy with insulin glargine or pioglitazone for 26 weeks. Echocardiographic data and blood samples were collected from the two groups before the start of the treatment and after 26 weeks. Left ventricular end-diastolic and left atrial end-systolic volumes were quantified, weight measured and blood samples analyzed. Results After 26 weeks of treatment, the changes in HbA1c, weight and haemoglobin were similar between the two groups. HDL increased significantly in the pioglitazone group. While there was an increase in natriuretic peptides in the pioglitazone group (NT-proBNP 11.4 ± 19.6 to 22.8 ± 44.0, p = 0.046, the difference between the treatment groups was not significant. Left ventricular end-diastolic volume increased by 11% and left atrial end-systolic volume by 17% in the pioglitazone group (Both, p Conclusion This randomised pilot-study showed that six-month treatment with pioglitazone induced significant increases in natriuretic peptides and alterations of cardiac size. These changes were not observed with insulin glargine, which also is known to induce fluid retention. Larger randomised trials are warranted to confirm these findings.

  9. The effect of pioglitazone and resistance training on body composition in older men and women undergoing hypocaloric weight loss.

    Science.gov (United States)

    Shea, M Kyla; Nicklas, Barbara J; Marsh, Anthony P; Houston, Denise K; Miller, Gary D; Isom, Scott; Miller, Michael E; Carr, J Jeffrey; Lyles, Mary F; Harris, Tamara B; Kritchevsky, Stephen B

    2011-08-01

    Age-related increases in ectopic fat accumulation are associated with greater risk for metabolic and cardiovascular diseases, and physical disability. Reducing skeletal muscle fat and preserving lean tissue are associated with improved physical function in older adults. PPARγ-agonist treatment decreases abdominal visceral adipose tissue (VAT) and resistance training preserves lean tissue, but their effect on ectopic fat depots in nondiabetic overweight adults is unclear. We examined the influence of pioglitazone and resistance training on body composition in older (65-79 years) nondiabetic overweight/obese men (n = 48, BMI = 32.3 ± 3.8 kg/m(2)) and women (n = 40, BMI = 33.3 ± 4.9 kg/m(2)) during weight loss. All participants underwent a 16-week hypocaloric weight-loss program and were randomized to receive pioglitazone (30 mg/day) or no pioglitazone with or without resistance training, following a 2 × 2 factorial design. Regional body composition was measured at baseline and follow-up using computed tomography (CT). Lean mass was measured using dual X-ray absorptiometry. Men lost 6.6% and women lost 6.5% of initial body mass. The percent of fat loss varied across individual compartments. Men who were given pioglitazone lost more visceral abdominal fat than men who were not given pioglitazone (-1,160 vs. -647 cm(3), P = 0.007). Women who were given pioglitazone lost less thigh subcutaneous fat (-104 vs. -298 cm(3), P = 0.002). Pioglitazone did not affect any other outcomes. Resistance training diminished thigh muscle loss in men and women (resistance training vs. no resistance training men: -43 vs. -88 cm(3), P = 0.005; women: -34 vs. -59 cm(3), P = 0.04). In overweight/obese older men undergoing weight loss, pioglitazone increased visceral fat loss and resistance training reduced skeletal muscle loss. Additional studies are needed to clarify the observed gender differences and evaluate how these changes in body composition influence functional status.

  10. Possible link of pioglitazone with bladder cancer in Japanese patients with type 2 diabetes.

    Science.gov (United States)

    Fujimoto, Kanta; Hamamoto, Yoshiyuki; Honjo, Sachiko; Kawasaki, Yukiko; Mori, Kanako; Tatsuoka, Hisato; Matsuoka, Atsuko; Wada, Yoshiharu; Ikeda, Hiroki; Fujikawa, Jun; Koshiyama, Hiroyuki

    2013-02-01

    We retrospectively examined the frequency of bladder cancer in Japanese patients with type 2 diabetes in relation to use of pioglitazone. Among a total of 663 patients identified to be taking pioglitazone, 9 had bladder cancer (1.36%). Overall the hazard ratio of 1.75 [95% CI: 0.89-3.45] for pioglitazone for bladder cancer was not significant. However the prevalence of bladder cancer was 2.10% in patients taking pioglitazone for less than 24 months which was significant increased (HR 2.73 [95% CI: 1.11-6.72]).

  11. Risk of cardiovascular disease and all-cause mortality among diabetic patients prescribed rosiglitazone or pioglitazone: a meta-analysis of retrospective cohort studies

    Institute of Scientific and Technical Information of China (English)

    CHEN Xin; YANG Li; ZHAI Suo-di

    2012-01-01

    Background The difference of cardiovascular effects between rosiglitazone and pioglitazone treatment for diabetic patients has not been thoroughly studied.We performed a meta-analysis to compare the risk of cardiovascular adverse effects in patients with type 2 diabetes treated with rosiglitazone compared to pioglitazone.Methods The Cochrane Library,PubMed,and Embase were searched to identify retrospective cohort studies assessing cardiovascular outcomes with rosiglitazone and pioglitazone.Meta-analysis of retrospective cohort studies was conducted using RevMan 5.0 software to calculate risk ratios.Results Of the 74 references identified,eight studies involving 945 286 patients fit the inclusion criteria for the analysis.The results of meta-analyses showed that,compared with pioglitazone,rosiglitazone therapy significantly increased the risk of myocardial infarction (risk ratios (RR) 1.17,95% confidence interval (CI) 1.04-1.32; P=0.01),the risk of heart failure (RR 1.18,95% CI 1.02-1.36; P=0.03),and total mortality (RR 1.13,95% CI 1.08-1.20; P <0.00001).Conclusion Compared with pioglitazone,rosiglitazone was associated with an increased risk of myocardial infarction,heart failure,and all-cause mortality in diabetic patients.

  12. Pioglitazone promotes preadipocyte proliferation by downregulating p16{sup Ink4a}

    Energy Technology Data Exchange (ETDEWEB)

    Hasan, Arif U. [Department of Cardiorenal Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan); Ohmori, Koji, E-mail: komori@med.kagawa-u.ac.jp [Department of Cardiorenal Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan); Hashimoto, Takeshi [Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan); Kamitori, Kazuyo; Hirata, Yuko [Department of Cell Physiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan); Ishihara, Yasuhiro; Okamoto, Naoko; Noma, Takahisa [Department of Cardiorenal Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan); Kosaka, Hiroaki [Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan); Tokuda, Masaaki [Department of Cell Physiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan); Kohno, Masakazu [Department of Cardiorenal Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan)

    2011-07-29

    Highlights: {yields} Mechanisms for preadipocyte hyperplasia by pioglitazone, a PPAR{gamma} agonist, are shown. {yields} Pioglitazone promotes cell-cycle of 3T3-L1 preadipocytes and increases their number. {yields} Pioglitazone downregulates a cyclin dependent kinase inhibitor, p16{sup Ink4a}. {yields} PPAR{gamma} transrepresses p16{sup Ink4a} gene in preadipocytes, which pioglitazone enhances. -- Abstract: Pioglitazone, a synthetic ligand of peroxisome proliferator-activated receptor (PPAR){gamma}, causes preadipocyte proliferation through a mechanism which still remains elusive. Here, to address the mechanism, we investigated the effects of PPAR{gamma} and pioglitazone on the kinetics of cyclin-dependent kinase inhibitors, especially with p16{sup Ink4a} (p16) centered, by employing 3T3-L1 preadipocytes. Pioglitazone promoted preadipocyte proliferation by increasing S and G{sub 2}/M cell-cycle entry, which was accompanied by decreased p16 mRNA expression. PPAR{gamma} overexpression along with the luciferase reporter assay confirmed that PPAR{gamma} was crucial for the downregulation of p16 mRNA transcription, and that the action was augmented by pioglitazone. Thus, pioglitazone exerted cell-cycle dependent promoting effect on preadipocyte proliferation, of which mechanisms include p16-downregulation through PPAR{gamma}.

  13. [Insulin sensitizer--anti-diabetic drugs, metformin and pioglitazone that can improve insulin resistance].

    Science.gov (United States)

    Korenaga, Masaaki; Kawaguchi, Koutaro; Korenaga, Keiko; Uchida, Kouichi; Sakaida, Iso

    2006-06-01

    Nonalcoholic steatohepatitis (NASH), which is considered the hepatic manifestation of the metabolic syndrome is an increasingly cause of chronic liver disease in Japan. NASH is finally lead to liver cirrhosis and hepatocellular carcinoma as viral hepatitis, therefore, medical treatment should be considered, when NASH occurs. Treatment of patients with metabolic syndrome has been focused on the management of associated conditions such as obesity, hyperlipidemia, hypertension and hyperinsulinemia. Insulin resistance, that could accelerate liver inflammation and fibrosis by up-regulation of TNFa seems to be most important factor in many cases of NASH. The insulin-sensitizing drugs, which were biguanides (metformin) and thiazolidinediones (pioglitazone) have been shown to correct not only insulin resistance but also steatosis and inflammation in the liver. Metformin and pioglitazone might be useful drugs against NASH, however further investigations were needed.

  14. Protective effect of pioglitazone on cardiomyocyte apoptosis in low-dose streptozotocin & high-fat diet-induced type-2 diabetes in rats

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    Uma Bhandari

    2015-01-01

    Full Text Available Background & objectives: Cardiomyocyte apoptosis is one of the pathologic phenomena associated with diabetes and related conditions including obesity, insulin resistance and hyperlipidaemia. In the present study, the protective effects of pioglitazone on cardiomyocyte apoptosis was evaluated in experimental diabetes induced by low dose of streptozoticin (STZ combined with high fat diet (HFD in rats. Methods: Male Wistar rats (150-200 g were injected with low-dose STZ (45 mg/kg, i.v., single dose and orally fed with a HFD (20 g/day/rat for a period of 28 days and simultaneously treated with pioglitazone (20 mg/kg/p.o. for a period of 21 days (from 8 th day to 28 th day. On 29 th day blood was collected, serum separated and used for biochemical parameters. Heart tissue was used for cardiomyocyte apoptosis measurement and also for histopathological examination. Results: Pioglitazone treatment resulted in a decrease in cardiomyocyte apoptosis as revealed by a decrease in cardiac caspase-3, lactate dehydrogenase (LDH levels and DNA fragmentation, and an increase in Na+K+ATPase levels in diabetic rats. Cardiac histology of diabetic control rats showed dense focal fatty infiltration in the myocardial cells whereas normal architecture with regular morphology and well preserved cytoplasm was observed with pioglitazone treatment. Pioglitazone treatment significantly reduced the heart rate, mean arterial blood pressure, body mass index (BMI and levels of serum glucose, leptin, insulin, HOMA-IR, total cholesterol (TC and triglycerides (TGs, apoliproprotein-B glycosylated haemoglobin (HbA1c levels and atherogenic index, and increased the levels of serum high density lipoprotein cholesterol (HDL-C and cardiac antioxidant enzymes. Interpretation & conclusions: The present study results suggest that pioglitazone possesses cardiac anti-apoptotic potential in diabetic rat model and can be further explored for its use for treatment of diabetic cardiomyopathy.

  15. Pioglitazone Upregulates Angiotensin Converting Enzyme 2 Expression in Insulin-Sensitive Tissues in Rats with High-Fat Diet-Induced Nonalcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2014-01-01

    Full Text Available Background and Aim. Thiazolidinediones (TZDs can improve hepatic steatosis in nonalcoholic steatohepatitis (NASH. Angiotensin (Ang II, the primary effector of renin-angiotensin system (RAS, plays vital roles in the development and progression of NASH. And some AngII-mediated effects can be regulated by TZDs. Angiotensin-converting enzyme (ACE 2, a new component of RAS, can degrade Ang II to attenuate its subsequent physiological actions. We aimed to evaluate the effects of TZDs on ACE2 expression in insulin-sensitive tissues in NASH rats. Methods. Forty rats were divided into the normal control, high-fat diet (HFD, pioglitazone control, and HFD plus pioglitazone groups. After 24 weeks of treatment, we evaluated changes in liver histology and tissue-specific ACE2 expression. Results. ACE2 gene and protein expression was significantly greater in liver and adipose tissue in the HFD group compared with normal control group, while was significantly reduced in skeletal muscle. Pioglitazone significantly reduced the degree of hepatic steatosis compared with the HFD group. Pioglitazone significantly increased ACE2 protein expression in liver, adipose tissue, and skeletal muscle compared with the HFD group. Conclusions. Pioglitazone improves hepatic steatosis in the rats with HFD-induced NASH and upregulates ACE2 expression in insulin-sensitive tissues.

  16. Leptin replacement improves postprandial glycemia and insulin sensitivity in human immunodeficiency virus-infected lipoatrophic men treated with pioglitazone: a pilot study.

    Science.gov (United States)

    Magkos, Faidon; Brennan, Aoife; Sweeney, Laura; Kang, Eun Seok; Doweiko, John; Karchmer, Adolf W; Mantzoros, Christos S

    2011-07-01

    Highly active antiretroviral therapy (HAART)-induced lipoatrophy is characterized by hypoleptinemia and insulin resistance. Evidence suggests that pioglitazone and recombinant methionyl human leptin (metreleptin) administration has beneficial effects in human immunodeficiency virus (HIV)-infected lipoatrophic patients. This proof-of-concept study aimed at evaluating whether the combination of metreleptin and pioglitazone has favorable effects, above and beyond pioglitazone alone, on both metabolic outcomes and peripheral lipoatrophy in HIV-infected patients on HAART. Nine HIV-positive men with at least 6 months of HAART exposure, clinical evidence of lipoatrophy, and low leptin concentrations (≤4 ng/mL) were placed on pioglitazone treatment (30 mg/d per os) and were randomized to receive either metreleptin (0.04 mg/kg subcutaneously once daily; n = 5) or placebo (n = 4) for 3 months in a double-blinded fashion. Compared with placebo, metreleptin reduced fasting serum insulin concentration, increased adiponectin concentration, reduced the homeostasis model assessment index of insulin resistance, and attenuated postprandial glycemia in response to a mixed meal (all P ≤ .02), but did not affect trunk and peripheral fat mass. HIV control was not affected, and no major adverse effects were observed. Metreleptin administration in HIV-positive, leptin-deficient patients with lipoatrophy treated with pioglitazone improves postprandial glycemia and insulin sensitivity. Results from this pilot study should be confirmed in larger clinical trials.

  17. Pioglitazone upregulates angiotensin converting enzyme 2 expression in insulin-sensitive tissues in rats with high-fat diet-induced nonalcoholic steatohepatitis.

    Science.gov (United States)

    Zhang, Wei; Xu, Yi-Zhi; Liu, Bo; Wu, Rong; Yang, Ying-Ying; Xiao, Xiao-Qiu; Zhang, Xia

    2014-01-01

    Thiazolidinediones (TZDs) can improve hepatic steatosis in nonalcoholic steatohepatitis (NASH). Angiotensin (Ang) II, the primary effector of renin-angiotensin system (RAS), plays vital roles in the development and progression of NASH. And some AngII-mediated effects can be regulated by TZDs. Angiotensin-converting enzyme (ACE) 2, a new component of RAS, can degrade Ang II to attenuate its subsequent physiological actions. We aimed to evaluate the effects of TZDs on ACE2 expression in insulin-sensitive tissues in NASH rats. Forty rats were divided into the normal control, high-fat diet (HFD), pioglitazone control, and HFD plus pioglitazone groups. After 24 weeks of treatment, we evaluated changes in liver histology and tissue-specific ACE2 expression. ACE2 gene and protein expression was significantly greater in liver and adipose tissue in the HFD group compared with normal control group, while was significantly reduced in skeletal muscle. Pioglitazone significantly reduced the degree of hepatic steatosis compared with the HFD group. Pioglitazone significantly increased ACE2 protein expression in liver, adipose tissue, and skeletal muscle compared with the HFD group. Pioglitazone improves hepatic steatosis in the rats with HFD-induced NASH and upregulates ACE2 expression in insulin-sensitive tissues.

  18. Genotype Phenotype Correlation of Genetic Polymorphism of PPAR Gamma Gene and Therapeutic Response to Pioglitazone in Type 2 Diabetes Mellitus- A Pilot Study

    Science.gov (United States)

    Sankaran, Ramalingam; Ramalingam, Sudha; Sairam, Thiagarajan; Somasundaram, LS

    2016-01-01

    Introduction Pro12Ala polymorphism is a missense mutation at codon 12 in peroxisome proliferator-activated receptor γ gene (PPARG). This polymorphism is known to be associated with increased insulin sensitivity. Pioglitazone, a thiazolidinedione, is an anti-diabetic drug which acts as an agonist at PPAR γ receptor. Aim To determine the association between Pro12Ala polymorphism of the PPARG and variation in therapeutic response to the PPARγ agonist, pioglitazone. Materials and Methods The study was done as a hospital based pilot project in 30 patients with type 2 diabetes mellitus, on treatment with sulfonylurea or metformin but without adequate glycaemic control. They were started on pioglitazone as add on therapy for a period of 12 weeks. The participants were categorized as responders and non-responders based on the change in HbA1C level after 12 weeks. Pro12Ala polymorphism was analysed by polymerase chain reaction-restriction fragment length polymorphism. Statistical Analysis Logistic regression analysis was done to evaluate the associations between age, baseline body weight, BMI, waist circumference, waist-hip ratio and Pro12Ala variants with the response to pioglitazone. The p-valuePro12Ala polymorphism and glycaemic response to pioglitazone. PMID:27042481

  19. Pioglitazone can ameliorate insulin resistance in low-dose streptozotocin and high sucrose-fat diet induced obese rats

    Institute of Scientific and Technical Information of China (English)

    Shi-ying DING; Zhu-fang SHEN; Yue-teng CHEN; Su-juan SUN; Quan Liu; Ming-zhi XIE

    2005-01-01

    Aim: To investigate the effect of the peroxisome proliferator-activator receptor (PPAR)-γ agonist, pioglitazone, on insulin resistance in low-dose streptozotocin and high sucrose-fat diet induced obese rats. Methods: Normal female Wistar rats were injected intraperitoneally with low-dose streptozotocin (STZ, 30 mg/kg) and fed with a high sucrose-fat diet for 8 weeks. Pioglitazone (20 mg/kg) was administered orally to the obese and insulin-resistant rats for 28 d. Intraperitoneal glucose tolerance tests, insulin tolerance tests and gluconeogenesis tests were carried out over the last 14 d. At the end of d 28 of the treatment, serums were collected for biochemical analysis. Glucose transporter 4 (GLUT4) and insulin receptor substrate-1 (IRS-1) protein expression in the liver and skeletal muscle were detected using Western blotting. Results: Significant insulin resistance and obesity were observed in low-dose STZ and high sucrose-fat diet induced obese rats. Pioglitazone (20 mg/kg) treatment significantly decreased serum insulin,triglyceride and free fatty acid levels, and elevated high density lipoprotein-cholesterol (HDL-C) levels. Pioglitazone also lowered the lipid contents in the liver and muscles of rats undergoing treatment. Gluconeogenesis was inhibited and insulin sensitivity was improved markedly. The IRS-1 protein contents in the liver and skeletal muscles and the GLUT4 contents in skeletal muscle were elevated significantly. Conclusion: The data suggest that treatment with pioglitazone improves insulin sensitivity in low-dose STZ and high sucrose-fat diet induced obese rats. The insulin sensitizing effect may be associated with ameliorating lipid metabolism, reducing hyperinsulinemia, inhibiting gluconeogenesis, and increasing IRS-1 and GLUT4 protein expression in insulin-sensitive tissues.

  20. Effects of pioglitazone on expressions of matrix metalloproteinases 2 and 9 in kidneys of diabetic rats

    Institute of Scientific and Technical Information of China (English)

    董凤芹; 李红; 蔡卫民; 陶君; 李群; 阮昱; 郑芬萍; 张哲

    2004-01-01

    Background The changes in matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expressions were examined in the kidneys of diabetic rats to investigate the degradative pathway of collagen type Ⅳ (C-Ⅳ) and the protective effects of pioglitazone on an experimental model of diabetic nephropathy.Methods In 54 SD rats used in our study, 18 served as normal controls. Diabetes mellitus was induced in 36 age- and weight-matched rats by intraperitoneal injection of streptozotocin (70 mg/kg); 18 of the diabetic rats were allocated at random to receive pioglitazone (20 mg*kg-1*d-1) in their drinking water and 18 served as diabetic controls. Rats were killed after 2, 4, or 8 weeks of treatment. Kidneys were examined pathomorphologically and the expressions of MMP-2, MMP-9, and C-Ⅳ were analyzed by immunohistochemistry, and the results were quantified by image analysis techniques.Results Diabetes mellitus was associated with a decrease in the expression of MMP-2 in the glomeruli (P0.05, vs control). The expression of MMP-9 did not show any change when comparing the three groups (P>0.05, vs control). STZ-diabetic rats were also associated with an increase in the expression of C-Ⅳ in the glomeruli and the interstitium (P<0.05, vs control). All diabetes-associated changes in MMP-2 expression were attenuated by pioglitazone treatment in association with reduced C-Ⅳ accumulation. Conclusions These results indicate that a decrease in MMP-2 expression in the glomeruli of diabetic rats may lead to impairment of C-Ⅳ degradation and contribute to the matrix accumulation in diabetic nephropathy. Pioglitazone treatment, which can attenuate the decrease of glomerular MMP-2 and the increase of C-Ⅳ degradation, has curative effects on diabetic nephropathy.

  1. Pioglitazone, a PPARγ agonist, provides comparable protection to angiotensin converting enzyme inhibitor ramipril against adriamycin nephropathy in rat.

    Science.gov (United States)

    Ochodnicky, Peter; Mesarosova, Lucia; Cernecka, Hana; Klimas, Jan; Krenek, Peter; Goris, Maaike; van Dokkum, Richard P E; Henning, Robert H; Kyselovic, Jan

    2014-05-05

    Peroxisome proliferator-activated receptor γ (PPARγ) agonists have been shown to ameliorate diabetic nephropathy, but much less are known about their effects in non-diabetic nephropathies. In the present study, metabolic parameters, blood pressure, aortic endothelial function along with molecular and structural markers of glomerular and tubulointerstitial renal damage, were studied in a rat model of normotensive nephropathy induced by adriamycin and treated with PPARγ agonist pioglitazone (12mg/kg, po), angiotensin converting enzyme (ACE) inhibitor ramipril (1mg/kg, po) or their combination. Pioglitazone had no effect on systolic blood pressure, marginally reduced glycemia and improved aortic endothelium-dependent relaxation. In the kidney, pioglitazone prevented the development of proteinuria and focal glomerulosclerosis to the similar extent as blood-pressure lowering ramipril. Renoprotection provided by either treatment was associated with a reduction in the cortical expression of profibrotic plasminogen activator inhibitor-1 and microvascular damage-inducing endothelin-1, and a limitation of interstitial macrophage influx. Treatment with PPARγ agonist, as well as ACE inhibitor comparably affected renal expression of the renin-angiotensin system (RAS) components, normalizing increased renal expression of ACE and enhancing the expression of Mas receptor. Interestingly, combined pioglitazone and ramipril treatment did not provide any additional renoprotection. These results demonstrate that in a nondiabetic renal disease, such as adriamycin-induced nephropathy, PPARγ agonist pioglitazone provides renoprotection to a similar extent as an ACE inhibitor by interfering with the expression of local RAS components and attenuating related profibrotic and inflammatory mechanisms. The combination of the both agents, however, does not lead to any additional renal benefit.

  2. Protective effects of fish oil and pioglitazone on pancreatic tissue in obese KK mice with type 2 diabetes.

    Science.gov (United States)

    Iizuka, Yuzuru; Kim, Hyounju; Izawa, Takuya; Sakurai, Koji; Hirako, Satoshi; Wada, Masahiro; Matsumoto, Akiyo

    2016-12-01

    n-3 Polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have protective effects against the pancreatic β-cell dysfunction through several mechanisms. Thiazolidines are insulin sensitizers and are used in treating patients with type 2 diabetes. Our previous study demonstrated that a combination of fish oil, which is rich with EPA and DHA, and pioglitazone exerts beneficial effects on obesity and diabetes through their actions on the liver and adipose tissue. However, it remains largely unknown whether such combination therapy affects the pancreas. To answer this question, KK mice, which serve as a model for obesity and type 2 diabetes, were treated for 8 weeks with fish oil and pioglitazone. The combined regimen suppressed pancreatic islet hypertrophy (mean islet area decreased by an average of 49% vs. control) compared with mice treated with fish oil or pioglitazone alone (decreased by an average of 21% and 32% vs. control, respectively). Compared with the controls, individual or combined treatment significantly increased the percentage of β-cell area in the pancreatic islets, significantly decreased endoplasmic reticulum stress, and reduced the percentage of apoptotic cell death in the pancreatic islets. These findings suggest that fish oil and/or pioglitazone prevents β-cell dysfunction by improving the insulin resistance and decreasing the ER stress.

  3. Pioglitazone alleviates cardiac and vascular remodelling and improves survival in monocrotaline induced pulmonary arterial hypertension.

    Science.gov (United States)

    Behringer, Arnica; Trappiel, Manuela; Berghausen, Eva Maria; Ten Freyhaus, Henrik; Wellnhofer, Ernst; Odenthal, Margarete; Blaschke, Florian; Er, Fikret; Gassanov, Natig; Rosenkranz, Stephan; Baldus, Stephan; Kappert, Kai; Caglayan, Evren

    2016-04-01

    Pulmonary arterial hypertension (PAH) is a fatal disease with limited therapeutic options. Pathophysiological changes comprise obliterative vascular remodelling of small pulmonary arteries, elevated mean pulmonary arterial systolic pressure (PASP) due to elevated resistance of pulmonary vasculature, adverse right ventricular remodelling, and heart failure. Recent findings also indicate a role of increased inflammation and insulin resistance underlying the development of PAH. We hypothesized that treatment of this condition with the peroxisome proliferator-activated receptor-γ (PPARγ) activator pioglitazone, known to regulate the expression of different genes addressing insulin resistance, inflammatory changes, and vascular remodelling, could be a beneficial approach. PAH was induced in adult rats by a single subcutaneous injection of monocrotaline (MCT). Pioglitazone was administered for 2 weeks starting 3 weeks after MCT-injection. At day 35, hemodynamics, organ weights, and -indices were measured. We performed morphological and molecular characterization of the pulmonary vasculature, including analysis of the degree of muscularization, proliferation rates, and medial wall thickness of the small pulmonary arteries. Furthermore, markers of cardiac injury, collagen content, and cardiomyocyte size were analyzed. Survival rates were monitored throughout the experimental period. Pioglitazone treatment improved survival, reduced PASP, muscularization of small pulmonary arteries, and medial wall thickness. Further, MCT-induced right ventricular hypertrophy and fibrosis were attenuated. This was accompanied with reduced cardiac expression of brain natriuretic peptide, as well as decreased cardiomyocyte size. Finally, pulmonary macrophage content and osteopontin gene expression were attenuated. Based on the beneficial impact of pioglitazone, activation of PPARγ might be a promising treatment option in PAH.

  4. Regulation of insulin degrading enzyme activity by obesity-associated factors and pioglitazone in liver of diet-induced obese mice.

    Directory of Open Access Journals (Sweden)

    Xiuqing Wei

    Full Text Available Insulin degrading enzyme (IDE is a potential drug target in the treatment of type 2 diabetes (T2D. IDE controls circulating insulin through a degradation-dependent clearance mechanism in multiple tissues. However, there is not sufficient information about IDE regulation in obesity. In this study, we test obesity-associated factors and pioglitazone in the regulation of IDE in diet-induced obese (DIO C57BL/6 mice. The enzyme activity and protein level of IDE were increased in the liver of DIO mice. Pioglitazone (10 mg/kg/day administration for 2 months significantly enhanced the enzyme activity (75%, protein (180% and mRNA (100% of IDE in DIO mice. The pioglitazone-induced changes were coupled with 50% reduction in fasting insulin and 20% reduction in fasting blood glucose. The mechanism of IDE regulation in liver was investigated in the mouse hepatoma cell line (Hepa 1c1c7 cells, in which pioglitazone (5 µM increased IDE protein and mRNA in a time-dependent manner in an 8 h study. Free fatty acid (palmitate 300 µM induced IDE protein, but reduced the mRNA. Glucagon induced, and TNF-α decreased IDE protein. Insulin did not exhibit any activity in the same condition. In summary, pioglitazone, FFA and glucagon directly increased, but TNF-α decreased the IDE activity in hepatocytes. The results suggest that IDE activity is regulated in liver by multiple factors in obesity and pioglitazone may induce IDE activity in the control of T2D.

  5. Pioglitazone, quercetin and hydroxy citric acid effect on hepatic biomarkers in Non Alcoholic Steatohepatitis

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    Krishna Mohan Surapaneni

    2014-01-01

    Full Text Available Background: Non alcoholic steatohepatitis (NASH, severe form of diseases belonging to the spectrum of the Non alcoholic fatty liver disease (NAFLD. It is an asymptomatic disease which leads to fibrosis and finally to cirrhosis, an end stage liver disease. Objective: To study the effect of pioglitazone, quercetin and hydroxy citric acid on hepatic biomarkers and various biochemical parameters in experimentally induced non alcoholic steatohepatitis (NASH. Materials and Methods: Male Wister rats were divided into 8 groups. The activities of alkaline phosphatase (ALP, aspartate transaminase (AST, alanine transaminase (ALT, lactate dehydrogenase (LDH and γ-Glutamyl Transferase (GGT were assayed in serum. The levels of various other biochemical parameters such as serum albumin, total bilirubin, creatinine, urea, uric acid and glucose were also estimated in experimental NASH. Results: The NASH group produced severe liver injury by significantly increasing the serum levels of ALT, AST, GGT and LDH compared with that of the control. However, the experimental NASH rats treated with pioglitazone, with quercetin and with hydroxy citric acid showed an obvious decrease in ALT, AST, GGT and LDH levels when compared with that of NASH induced group. A significant increase in the levels of albumin, creatinine, urea, uric acid, glucose and total bilirubin was noticed in experimentally induced NASH group (group 2 when compared to rats in control group (group 1. Conclusion: It could be inferred from this study that, pioglitazone, quercetin and hydroxy citric acid may afford protection to the liver against NASH, as evidenced by the results of this study on the levels of various biochemical parameters such as glucose, urea, uric acid, creatinine and bilirubin. Whereas from the results of hepatic marker enzymes, it is evident that optimal protection was observed after quercetin treatment against experimental NASH whereas pioglitazone and hydroxy citric acid also

  6. A cost-effectiveness analysis of pioglitazone plus metformin compared with rosiglitazone plus metformin from a third-party payer perspective in the US.

    Science.gov (United States)

    St Charles, Meaghan; Minshall, Michael E; Pandya, Bhavik J; Baran, Robert W; Tunis, Sandra L

    2009-06-01

    . Pioglitazone plus metformin was no longer dominant with 0% discounting, with 25% reduction in its HbA(1c) effects, or with a 15% increase in its acquisition price. Under a range of assumptions and study limitations around cohorts, clinical effects, and treatment patterns, this long-term analysis showed that pioglitazone plus metformin, when compared to rosiglitazone plus metformin, was a dominant treatment strategy within the US payer setting. Results were driven by the combination of modest differences in QALYs and modest savings in total complication costs over 35 years.

  7. The peroxisome proliferator-activated receptor γ agonist pioglitazone preserves bone microarchitecture in experimental arthritis by reducing the interleukin-17-dependent osteoclastogenic pathway.

    Science.gov (United States)

    Koufany, Meriem; Chappard, Daniel; Netter, Patrick; Bastien, Claire; Weryha, Georges; Jouzeau, Jean-Yves; Moulin, David

    2013-12-01

    To investigate the effect of pioglitazone on inflammation-induced bone loss and changes in bone microarchitecture in rats with adjuvant-induced arthritis (AIA), focusing on the contribution of interleukin-17 (IL-17) and the balance of RANKL and osteoprotegerin (OPG). Male Lewis rats sensitized with Freund's complete adjuvant were treated orally for 21 days with 30 mg/kg/day of pioglitazone or vehicle. Arthritis severity was evaluated by clinical and histologic examination. Bone mineral density (BMD) was assessed by dual x-ray absorptiometry. The therapeutic effect of pioglitazone on changes of the bone architecture was determined by micro-computed tomography (micro-CT). Levels of RANKL, OPG, and IL-17 were determined by serum immunoassay and by synovial tissue immunohistochemistry. Messenger RNA for IL-17 and retinoic acid receptor-related orphan nuclear receptor γt (RORγt) was evaluated by quantitative reverse transcription-polymerase chain reaction and IL-17 promoter activity by gene-reporter assay. Micro-CT analysis revealed that pioglitazone treatment reduced arthritis severity and bone erosion scores and increased BMD in comparison to vehicle treatment. Cortical bone thickness was preserved, although the major beneficial effect of pioglitazone was on indices of the trabeculae, especially trabecular separation. Pioglitazone reduced the ratio of RANKL to OPG, in both the serum and the inflamed synovium. Circulating levels of IL-17 were significantly reduced by pioglitazone treatment, as were the percentages of IL-17-positive cells, mainly polymorphonuclear cells, in the inflamed synovium. Induction of IL-17 was strictly dependent on the binding of RORγt to IL-17 promoter, and lentiviral overexpression of peroxisome proliferator-activated receptor γ (PPARγ) reduced the expression of RORγt. Pioglitazone decreased the level of inflammatory bone destruction and protected the bone microarchitecture in rats with AIA by controlling the circulating and local

  8. Effect of method of preparation on pioglitazone HCl-β-cyclodextrin inclusion complexes

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    Beloshe Shrikant

    2010-01-01

    Full Text Available Pioglitazone HCl is an antidiabetic agent with poor aqueous solubility. Inclusion complexes of pioglitazone HCl were prepared with β-cyclodextrin using various methods (physical mixing, kneading method, co-precipitation. The main aim of the present invention is to study the effect of the method of preparation on the dissolution profiles of pioglitazone HCl-β-Cyclodextrin inclusion complexes . The phase solubility profile of pioglitazone HCl with β-cyclodextrin was classified as AL-type and stability constant with 1:1 molar ratio was 115.45, calculated from the phase solubility diagram. Formation of the inclusion complex between pioglitazone HCl and β-cyclodextrin was confirmed by the Fourier Transform Infrared (FT-IR spectroscopy. The dissolution profile of inclusion complexes were determined and compared with those of pioglitazone HCl alone and its physical mixtures. The dissolution rate of the pioglitazone HCl-β-cyclodextrin inclusion complex prepared by the co-precipitation method was six times higher when compared with the pure drug. The method of complexation of pioglitazone HCl in β-CD increased the dissolution rate of the drug in the following order: Coppt > KM > PM >Drug.

  9. Toxicological evaluation of subchronic use of pioglitazone in mice

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    Said Said Elshama

    2016-07-01

    Full Text Available Objective(s: Pioglitazone (Actos is one of the most controversial recent oral antidiabetic drugs. It was originally authorized in the European Union in 2000, and approved as an oral monotherapy for overweight second type of diabetic patients in 2002. It belongs to the thiazolidinedione group which some of its members have been withdrawn from the market due to the hepatotoxicity or cardiotoxicity effects.This studyinvestigates sub-chronic use of pioglitazone induced toxicity in mice by the assessment of renal and liver function tests, cardiac enzymes, and some hematological indices with histological changes of liver, kidney, heart, and bladder. Materials and Methods: 120 albino mice were divided into four groups; 30 in each. The first group (control received water, second (diabetic group received alloxan only, while the third and the fourth groups received alloxan with 200 and 400 mg/kg/day of pioglitazone, respectively for 90 days. Results: Prolonged use of pioglitazone induced significant abnormalities of hepatic, renal, and cardiac biomarkers and some hematological indices associated with histopathological changes in the liver, kidney, heart, and bladder that increased based on administered dose. Conclusion: Subchronic use of pioglitazone leads to hepatic, renal, cardiac, hematological, and bladder affection depending on the applied dose.

  10. Pioglitazone promotes preadipocyte proliferation by downregulating p16(Ink4a).

    Science.gov (United States)

    Hasan, Arif U; Ohmori, Koji; Hashimoto, Takeshi; Kamitori, Kazuyo; Hirata, Yuko; Ishihara, Yasuhiro; Okamoto, Naoko; Noma, Takahisa; Kosaka, Hiroaki; Tokuda, Masaaki; Kohno, Masakazu

    2011-07-29

    Pioglitazone, a synthetic ligand of peroxisome proliferator-activated receptor (PPAR)γ, causes preadipocyte proliferation through a mechanism which still remains elusive. Here, to address the mechanism, we investigated the effects of PPARγ and pioglitazone on the kinetics of cyclin-dependent kinase inhibitors, especially with p16(Ink4a) (p16) centered, by employing 3T3-L1 preadipocytes. Pioglitazone promoted preadipocyte proliferation by increasing S and G(2)/M cell-cycle entry, which was accompanied by decreased p16 mRNA expression. PPARγ overexpression along with the luciferase reporter assay confirmed that PPARγ was crucial for the downregulation of p16 mRNA transcription, and that the action was augmented by pioglitazone. Thus, pioglitazone exerted cell-cycle dependent promoting effect on preadipocyte proliferation, of which mechanisms include p16-downregulation through PPARγ. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Pioglitazone halts axonal degeneration in a mouse model of X-linked adrenoleukodystrophy.

    Science.gov (United States)

    Morató, Laia; Galino, Jorge; Ruiz, Montserrat; Calingasan, Noel Ylagan; Starkov, Anatoly A; Dumont, Magali; Naudí, Alba; Martínez, Juan José; Aubourg, Patrick; Portero-Otín, Manuel; Pamplona, Reinald; Galea, Elena; Beal, M Flint; Ferrer, Isidre; Fourcade, Stéphane; Pujol, Aurora

    2013-08-01

    X-linked adrenoleukodystrophy is a neurometabolic disorder caused by inactivation of the peroxisomal ABCD1 transporter of very long-chain fatty acids. In mice, ABCD1 loss causes late onset axonal degeneration in the spinal cord in association with locomotor disability resembling the most common phenotype in patients, adrenomyeloneuropathy. Increasing evidence indicates that oxidative stress and bioenergetic failure play major roles in the pathogenesis of X-linked adrenoleukodystrophy. In this study, we aimed to evaluate whether mitochondrial biogenesis is affected in X-linked adrenoleukodystrophy. We demonstrated that Abcd1 null mice show reduced mitochondrial DNA concomitant with downregulation of mitochondrial biogenesis pathway driven by PGC-1α/PPARγ and reduced expression of mitochondrial proteins cytochrome c, NDUFB8 and VDAC. Moreover, we show that the oral administration of pioglitazone, an agonist of PPARγ, restored mitochondrial content and expression of master regulators of biogenesis, neutralized oxidative damage to proteins and DNA, and reversed bioenergetic failure in terms of ATP levels, NAD+/NADH ratios, pyruvate kinase and glutathione reductase activities. Most importantly, the treatment halted locomotor disability and axonal damage in X-linked adrenoleukodystrophy mice. These results lend support to the use of pioglitazone in clinical trials with patients with adrenomyeloneuropathy and reveal novel molecular mechanisms of action of pioglitazone in neurodegeneration. Future studies should address the effects of this anti-diabetic drug on other axonopathies in which oxidative stress and mitochondrial dysfunction are contributing factors.

  12. Pioglitazone inhibition of lipopolysaccharide-induced nitric oxide synthase is associated with altered activity of p38 MAP kinase and PI3K/Akt

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    Hunter Randy

    2008-01-01

    Full Text Available Abstract Background Previous studies have suggested that peroxisome proliferator activated receptor-gamma (PPAR-γ-mediated neuroprotection involves inhibition of microglial activation and decreased expression and activity of inducible nitric oxide synthase (iNOS; however, the underlying molecular mechanisms have not yet been well established. In the present study we explored: (1 the effect of the PPAR-γ agonist pioglitazone on lipopolysaccharide (LPS-induced iNOS activity and nitric oxide (NO generation by microglia; (2 the differential role of p38 mitogen-activated protein kinase (p38 MAPK, c-Jun NH(2-terminal kinase (JNK, and phosphoinositide 3-kinase (PI3K on LPS-induced NO generation; and (3 the regulation of p38 MAPK, JNK, and PI3K by pioglitazone. Methods Mesencephalic neuron-microglia mixed cultures, and microglia-enriched cultures were treated with pioglitazone and/or LPS. The protein levels of iNOS, p38 MAPK, JNK, PPAR-γ, PI3K, and protein kinase B (Akt were measured by western blot. Different specific inhibitors of iNOS, p38MAPK, JNK, PI3K, and Akt were used in our experiment, and NO generation was measured using a nitrite oxide assay kit. Tyrosine hydroxylase (TH-positive neurons were counted in mesencephalic neuron-microglia mixed cultures. Results Our results showed that pioglitazone inhibits LPS-induced iNOS expression and NO generation, and inhibition of iNOS is sufficient to protect dopaminergic neurons against LPS insult. In addition, inhibition of p38 MAPK, but not JNK, prevented LPS-induced NO generation. Further, and of interest, pioglitazone inhibited LPS-induced phosphorylation of p38 MAPK. Wortmannin, a specific PI3K inhibitor, enhanced p38 MAPK phosphorylation upon LPS stimulation of microglia. Elevations of phosphorylated PPAR-γ, PI3K, and Akt levels were observed with pioglitazone treatment, and inhibition of PI3K activity enhanced LPS-induced NO production. Furthermore, wortmannin prevented the inhibitory effect of

  13. Impaired insulin-stimulated phosphorylation of Akt and AS160 in skeletal muscle of women with polycystic ovary syndrome is reversed by pioglitazone treatment

    DEFF Research Database (Denmark)

    Højlund, Kurt; Glintborg, Dorte; Andersen, Nicoline Resen

    2008-01-01

    OBJECTIVE: Insulin resistance in skeletal muscle is a major risk factor for type 2 diabetes in women with polycystic ovary syndrome (PCOS). However, the molecular mechanisms underlying skeletal muscle insulin resistance and the insulin-sensitizing effect of thiazolidinediones in PCOS in vivo...... in muscle of PCOS patients. Akt phosphorylation at Ser473 and Thr308 correlated positively with R(d) and NOGD in the insulin-stimulated state. Serum free testosterone was inversely related to insulin-stimulated R(d) and NOGD in PCOS. Importantly, the pioglitazone-mediated improvement in insulin....... CONCLUSIONS: Impaired insulin signaling through Akt and AS160 in part explains insulin resistance at the molecular level in skeletal muscle in PCOS, and the ability of pioglitazone to enhance insulin sensitivity involves improved signaling through Akt and AS160. Moreover, our data provide correlative evidence...

  14. Direct inhibitory effects of pioglitazone on hepatic fetuin-A expression.

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    Akinobu Ochi

    Full Text Available Fetuin-A, a circulating glycoprotein synthesized in the liver, is involved in insulin resistance and type 2 diabetes. However, regulation of fetuin-A synthesis has remained obscure. We previously reported that pioglitazone treatment significantly reduced serum fetuin-A levels in patients with type 2 diabetes. To clarify whether pioglitazone can directory inhibit hepatic fetuin-A synthesis, we investigated the effects of pioglitazone on fetuin-A expression both in vitro and in vivo. Pioglitazone treatment suppressed mRNA and protein expression of fetuin-A in Fao hepatoma cells. Interestingly, rosiglitazone but not metformin, also inhibited fetuin-A expression. In addition, GW 9662, an inhibitor of peroxisome proliferator-activated receptor (PPAR γ, reversed pioglitazone-induced suppression of fetuin-A, suggesting that thiazolidinedione derivatives may have common characteristics with regard to fetuin-A suppression, possibly through PPARγactivation. Finally, oral administration of pioglitazone to mice for 8 weeks resulted in suppression of hepatic fetuin-A mRNA. These findings suggest that pioglitazone may partially ameliorate insulin resistance through its direct inhibitory effects on fetuin-A expression in the liver.

  15. Direct inhibitory effects of pioglitazone on hepatic fetuin-A expression.

    Science.gov (United States)

    Ochi, Akinobu; Mori, Katsuhito; Emoto, Masanori; Nakatani, Shinya; Morioka, Tomoaki; Motoyama, Koka; Fukumoto, Shinya; Imanishi, Yasuo; Koyama, Hidenori; Ishimura, Eiji; Inaba, Masaaki

    2014-01-01

    Fetuin-A, a circulating glycoprotein synthesized in the liver, is involved in insulin resistance and type 2 diabetes. However, regulation of fetuin-A synthesis has remained obscure. We previously reported that pioglitazone treatment significantly reduced serum fetuin-A levels in patients with type 2 diabetes. To clarify whether pioglitazone can directory inhibit hepatic fetuin-A synthesis, we investigated the effects of pioglitazone on fetuin-A expression both in vitro and in vivo. Pioglitazone treatment suppressed mRNA and protein expression of fetuin-A in Fao hepatoma cells. Interestingly, rosiglitazone but not metformin, also inhibited fetuin-A expression. In addition, GW 9662, an inhibitor of peroxisome proliferator-activated receptor (PPAR) γ, reversed pioglitazone-induced suppression of fetuin-A, suggesting that thiazolidinedione derivatives may have common characteristics with regard to fetuin-A suppression, possibly through PPARγactivation. Finally, oral administration of pioglitazone to mice for 8 weeks resulted in suppression of hepatic fetuin-A mRNA. These findings suggest that pioglitazone may partially ameliorate insulin resistance through its direct inhibitory effects on fetuin-A expression in the liver.

  16. The association of pioglitazone and urinary tract disease in type 2 diabetic Taiwanese: bladder cancer and chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Mei-Yueh Lee

    Full Text Available OBJECTIVE: Although studies have shown an association between pioglitazone and bladder cancer, the associated factors have not been identified. The aim of this study was to investigate the factors that may link pioglitazone to bladder cancer. MATERIALS AND METHODS: In total, 34,970 study subjects were identified from the National Health Insurance Research Database in 2003 with follow-up from 2005 to 2009. The demographic characteristics of patients who had used and had never used pioglitazone, including age, sex, diabetes duration, urinary tract disease, nephropathy, bladder cancer, and cumulative dose and duration of pioglitazone therapy, were analyzed using the χ2 test. Cox proportional hazard regression models were used to determine the independent effects of pioglitazone on bladder cancer and newly developed chronic kidney disease. RESULTS: Among 3,497 ever users and 31,473 never users of pioglitazone, the respective incident cases of bladder cancer were 12 (0.4% and 72 (0.2%, and for newly developed chronic kidney disease 245 (8.1% and 663 (2.3%, respectively. Ever use of pioglitazone [1.59(1.32-1.91], cumulative dose of pioglitazone 10,500 mg [1.34 (1.04-1.73], and duration of therapy 12 months [1.39 (1.09-1.76] were associated with the development of chronic kidney disease. CONCLUSIONS: There was no association of pioglitazone use with bladder cancer development, however, there was an association with an increased risk of newly developed chronic kidney disease.

  17. Pioglitazone does not affect vascular or inflammatory responses after endotoxemia in humans.

    Science.gov (United States)

    Schaller, G; Kolodjaschna, J; Pleiner, J; Mittermayer, F; Kapiotis, S; Schmetterer, L; Wolzt, M

    2008-08-01

    PPARgamma agonists have been proposed to exert more than metabolic benefits, particularly by anti-inflammatory mechanisms. We hypothesized that pioglitazone might modulate inflammatory and vascular responses to lipopolysaccharide (LPS). In a placebo-controlled parallel-group study in 18 healthy male subjects, the E. coli endotoxin model of inflammation (20 IU/kg i. v.) was employed to test the effect of 60 mg pioglitazone over nine days on inflammatory cytokines. Macrovascular function and microvascular blood flow were assessed by brachial artery ultrasound and retinal blood flow parameters, respectively. Pioglitazone increased brachial artery diameter by 5.6% but had no effect on other outcome parameters under resting conditions. LPS increased cytokine levels to peak concentrations of 91.3+/-22.5 ng/ml (IL-6), 261.4+/-60.0 ng/ml (TNFalpha), and 524.5+/-15.3 ng/ml (VCAM-1). The endotoxin caused microvascular vasodilation and increased retinal white blood cell flux, while baseline brachial artery diameter remained unchanged. Pioglitazone had no effect on inflammatory cytokine or adhesion molecule release but mitigated LPS-induced hypotension (p<0.05). Neither brachial artery function nor microvascular blood flow was altered by pioglitazone. In conclusion, acute immune reactions to LPS are not affected by pioglitazone, which exerts subtle vascular effects alone and during endotoxemia. The anti-inflammatory properties of short-term pioglitazone to endotoxins in healthy subjects are therefore limited.

  18. Effect of creatine and pioglitazone on Hk-2 cell line cisplatin nephrotoxicity.

    Science.gov (United States)

    Genc, Gurkan; Kilinc, Veli; Bedir, Abdulkerim; Ozkaya, Ozan

    2014-08-01

    Cisplatin is a chemotherapeutic agent, which is used in the treatment of various solid organ cancers, and its main dose limiting side effect of cisplatin is nephrotoxicity. The aim of this study is to investigate the role of pioglitazone and creatine on cisplatin nephrotoxicity in vitro. Real-time cell analyzer system (RTCA) was used for real-time and time-dependent analysis of the cellular response of HK-2 cells following incubation with cisplatin and combination with creatine or pioglitazone hydrochloride. First, half-maximal inhibitory concentrations (IC50) of cisplatin, creatine and pioglitazone were calculated by RTCA system. Afterwards creatine and pioglitazone was administered with serial dilutions under RTCA system. IC50 dose for cisplatin was 7.69 M × 10(-5) at 24th hour and 3.93 M × 10(-6) at 48th hour. IC50 dose for pioglitazone was 1.61 M × 10(-3) at 24th hour and 2.85 M × 10(-4) at 48th hour. Although cells were treated the dose of 40,225 mM creatine, IC50 dose could not been reached. Neither pioglitazone nor creatine had additional protective effect in any dose. Consequently, beneficial effect of creatine and pioglitazone on cisplatin-induced cell death could not be found. Further studies and clinical trials are needed to evaluate the effect of different doses of these drugs in cisplatin-induced nephrotoxicity.

  19. Effects of sitagliptin or metformin added to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients.

    Science.gov (United States)

    Derosa, Giuseppe; Maffioli, Pamela; Salvadeo, Sibilla A T; Ferrari, Ilaria; Ragonesi, Pietro D; Querci, Fabrizio; Franzetti, Ivano G; Gadaleta, Gennaro; Ciccarelli, Leonardina; Piccinni, Mario N; D'Angelo, Angela; Cicero, Arrigo F G

    2010-06-01

    significant differences between the 2 groups. There was a significant correlation between HOMA-IR decrease and ADN increase, and between HOMA-IR decrease and R and TNF-alpha decrease in pioglitazone plus metformin group after the treatment. The addition of both sitagliptin or metformin to pioglitazone gave an improvement of HbA(1c), FPG, and PPG; but metformin led also to a decrease of body weight and to a faster and better improvement of insulin resistance and inflammatory state parameters, even if sitagliptin produced a better protection of beta-cell function.

  20. 吡格列酮与二甲双胍片治疗2型糖尿病的效果观察%Pioglitazone and Metformin for the Treatment of Type 2 Diabetes

    Institute of Scientific and Technical Information of China (English)

    任艳莉

    2015-01-01

    Objective To investigate the clinical efficacy of pioglitazone and metformin in patients with type 2 diabetes.Methods70 cases of type 2 diabetic patients were randomly divided into control group,observation group 35 cases,control group received metformin treatment,observation group metformin combined with pioglitazone treatment,compared to the treatment groups of patients and adverse events happening.ResultsThe two groups of patients after treatment 2 h PG,FPG,HbA1C indicators were significantly improved,but the observation group 2hPG,FPG,HbA1C and other indicators to improve the situation than the control group(P 0.05).Conclusion Pioglitazone and metformin in the treatment of type 2 diabetes in effect safe and effective,with application value.%目的:探讨吡格列酮与二甲双胍在治疗2型糖尿病中的临床效果。方法选取2型糖尿病患者70例,按随机数字表法分为对照组、观察组各35例,对照组采用二甲双胍治疗,观察组采用二甲双胍联合吡格列酮治疗,对比两组患者治疗效果及不良反应发生情况。结果两组患者治疗后2 h PG、FPG、HbA1C指标均改善,但观察组治疗后2 h PG、FPG、HbA1C等指标改善情况优于对照组(P0.05)。结论吡格列酮与二甲双胍联合应用在治疗2型糖尿病中安全有效。

  1. A Pilot Trial of Pioglitazone HCl and Tretinoin in ALS: Cerebrospinal Fluid Biomarkers to Monitor Drug Efficacy and Predict Rate of Disease Progression

    Directory of Open Access Journals (Sweden)

    Todd D. Levine

    2012-01-01

    Full Text Available Objectives. To determine if therapy with pioglitazone HCl and tretinoin could slow disease progression in patients with ALS. Levels of tau and pNFH in the cerebrospinal fluid were measured to see if they could serve as prognostic indicators. Methods. 27 subjects on stable doses of riluzole were enrolled. Subjects were randomized to receive pioglitazone 30 mg/d and tretinoin 10 mg/BID for six months or two matching placebos. ALSFRS-R scores were followed monthly. At baseline and at the final visit, lumbar punctures (LPs were performed to measure cerebrospinal fluid (CSF biomarker levels. Results. Subjects treated with tretinoin, pioglitazone, and riluzole had an average rate of decline on the ALSFRS-R scale of −1.02 points per month; subjects treated with placebo and riluzole had a rate of decline of -.86 (P=.18. Over six months of therapy, CSF tau levels decreased in subjects randomized to active treatment and increased in subjects on placebo. Further higher levels of pNF-H at baseline correlated with a faster rate of progression. Conclusion. ALS patients who were treated with tretinoin and pioglitazone demonstrated no slowing on their disease progression. Interestingly, the rate of disease progression was strongly correlated with levels of pNFH in the CSF at baseline.

  2. Pioglitazone and the risk of bladder cancer: An Indian retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Sunil Gupta

    2015-01-01

    Full Text Available Aim: To determine whether pioglitazone is associated with an increased risk of bladder cancer among Indian type 2 diabetic patients. Methods: A retrospective data analysis of 2222 type 2 diabetic patients was conducted. The study subjects were divided into two equal groups: 1111 pioglitazone users and 1111 pioglitazone non-users. The safety of pioglitazone therapy was analyzed in terms of occurrence of bladder and other types of cancers along with its efficacy in terms of glycemic control. Parameters for assessing safety were duration of disease, duration of usage and total dose of pioglitazone consumed across age groups, glycemic control, obesity and family history of any cancer. Bladder cancer prevalence was analyzed on the basis of urinary cytology, urine routine and microscopy, hematuria, urinary nuclear matrix protein 22 analysis and ultrasonography. Results: Of the 2222 cases analysed, there was no evidence of bladder cancer in any of the studied groups, (p=not significant which was also evident among 1111 patients on Pioglitazone therapy with a cumulative dose consumption of 2737 mg to 1,31,400 mg. On subgroup analysis, there was no evidence of bladder cancer amongst patients with age >60 years, duration of diabetes > 10 years and uncontrolled diabetics (HbA1c >8% with cumulative pioglitazone consumption of >28,000 mg. A significant number of patients achieved good glycemic control (HbA1c <7.5% with pioglitazone therapy. Conclusion: Pioglitazone therapy was not associated with occurrence of bladder cancer among Indian type 2 diabetic patients and demonstrated good glycemic control.

  3. A single dose of PPARγ agonist pioglitazone reduces cortical oxidative damage and microglial reaction following lateral fluid percussion brain injury in rats.

    Science.gov (United States)

    Pilipović, Kristina; Župan, Željko; Dolenec, Petra; Mršić-Pelčić, Jasenka; Župan, Gordana

    2015-06-03

    Neuroprotective actions of the peroxisome proliferator-activated receptor-γ (PPARγ) agonists have been observed in various animal models of the brain injuries. In this study we examined the effects of a single dose of pioglitazone on oxidative and inflammatory parameters as well as on neurodegeneration and the edema formation in the rat parietal cortex following traumatic brain injury (TBI) induced by the lateral fluid percussion injury (LFPI) method. Pioglitazone was administered in a dose of 1mg/kg at 10min after the brain trauma. The animals of the control group were sham-operated and injected by vehicle. The rats were decapitated 24h after LFPI and their parietal cortices were analyzed by biochemical and histological methods. Cortical edema was evaluated in rats sacrificed 48h following TBI. Brain trauma caused statistically significant oxidative damage of lipids and proteins, an increase of glutathione peroxidase (GSH-Px) activity, the cyclooxygenase-2 (COX-2) overexpression, reactive astrocytosis, the microglia activation, neurodegeneration, and edema, but it did not influence the superoxide dismutase activity and the expressions of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha in the rat parietal cortex. Pioglitazone significantly decreased the cortical lipid and protein oxidative damage, increased the GSH-Px activity and reduced microglial reaction. Although a certain degree of the TBI-induced COX-2 overexpression, neurodegeneration and edema decrease was detected in pioglitazone treated rats, it was not significant. In the injured animals, cortical reactive astrocytosis was unchanged by the tested PPARγ agonist. These findings demonstrate that pioglitazone, administered only in a single dose, early following LFPI, reduced cortical oxidative damage, increased antioxidant defense and had limited anti-inflammatory effect, suggesting the need for further studies of this drug in the treatment of TBI.

  4. 吡格列酮与厄贝沙坦联合在早期2型糖尿病肾病治 的临床应用分析%Analysis of the clinical application of Pioglitazone combined with irbesartan in treatment of early diabetic nephropathy in type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    纪月霞; 刘冬梅; 李平

    2012-01-01

    Pioglitazone combined with irbesartan in treatment of early diabetic nephropathy in type 2 diabetes mellitus can play a synergistic effect, increase the curative effect, reduce blood sugar, improve renal function, and be worthy of clinical application and discussion.

  5. 吡格列酮治疗2型糖尿病临床疗效观察%Comparision of effect of pioglitazone and metformin in treatment of type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    褚秀英

    2009-01-01

    目的 比较吡格列酮和二甲双胍在降血糖、降血脂、降血压及改善胰岛素敏感性的作用.方法 采用随机对照研究.共选择60例2型糖尿病患者,分为两组,对照组(30例)给予二甲双胍500 mg,口服,每日2次;试验组(30例)给予吡格列酮30 mg,口服,每日1次.疗程均为12周,观察两组治疗前后血糖、血脂、血压、胰岛素等指标的变化.结果 治疗后两组血糖、糖化血红蛋白均明显下降(P<0.01),组间比较差异无统计学意义(P>0.05).试验组胰岛素、C肽均明显下降(P<0.01),对照组餐后2 h胰岛素下降(P<0.05).试验组三酰甘油、游离脂肪酸明显下降,高密度脂蛋白-胆固醇较治疗前升高(P均<0.01).对照组血脂各项较治疗前明显变化(P均<0.01),两组间比较,总胆固醇和低密度脂蛋白-胆固醇变化比较差异有统计学意义(P<0.05),但两组不良反应发生率比较差异无统计学意义(P>0.05).结论 吡格列酮和二甲双胍具有相似的降血糖、调脂作用,而吡格列酮还有改善外周组织胰岛素敏感性及降血压的作用.%Objective To compare the effect of pioglitazone and metformin in dereasing blood glucose,blood fat and improving insulin sensitivity.Methods The parallel randomized control clinical trial was used.Sixty patients with type 2 diabetes mellitus were divided into treatment group and control group.The patients of control group took mefformin 500 mg,po,bid for 12 weeks.The patients of treatment group took pioglitazone 30 mg,po,qd for 12 weeks.The changes of blood glucose,blood fat and insulin before and after treatment between two groups were observed.Results The blood glucose and glycosy-lated hemoglobin (HbA1c) after treatment in two groups significantly reduced (P<0.01).Insulin and C-peptide reduced in treatment group (P<0.01).As to control group,postprandial insulin reduced (P<0.05).The triglycerides and the free fat acid reduce in treatment group

  6. Pioglitazone normalizes insulin signaling in the diabetic rat retina through reduction in tumor necrosis factor α and suppressor of cytokine signaling 3.

    Science.gov (United States)

    Jiang, Youde; Thakran, Shalini; Bheemreddy, Rajini; Ye, Eun-Ah; He, Hui; Walker, Robert J; Steinle, Jena J

    2014-09-19

    Dysfunctional insulin signaling is a key component of type 2 diabetes. Little is understood of the effects of systemic diabetes on retinal insulin signaling. A number of agents are used to treat patients with type 2 diabetes to normalize glucose levels and improve insulin signaling; however, little has been done to investigate the effects of these agents on retinal insulin signal transduction. We hypothesized that pioglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) agonist, would normalize retinal insulin signal transduction through reduced tumor necrosis factor α (TNFα) and suppressor of cytokine signaling 3 (SOCS3) activities in whole retina and retinal endothelial cells (REC) and Müller cells. To test this hypothesis, we used the BBZDR/Wor type 2 diabetic rat model, as well as REC and Müller cells cultured in normoglycemia and hyperglycemic conditions, to investigate the effects of pioglitazone on TNFα, SOCS3, and downstream insulin signal transduction proteins. We also evaluated pioglitazone's effects on retinal function using electroretinogram and markers of apoptosis. Data demonstrate that 2 months of pioglitazone significantly increased electroretinogram amplitudes in type 2 diabetic obese rats, which was associated with improved insulin receptor activation. These changes occurred in both REC and Müller cells treated with pioglitazone, suggesting that these two cell types are key to insulin resistance in the retina. Taken together, these data provide evidence of impaired insulin signaling in type 2 diabetes rats, which was improved by increasing PPARγ activity. Further investigations of PPARγ actions in the retina may provide improved treatment options.

  7. 吡格列酮联合胰岛素治疗2型糖尿病的疗效观察%Curative effect observation of pioglitazone combined with insulin in the treatment of type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    冯翠娥

    2014-01-01

    目的:观察吡格列酮联合胰岛素治疗2型糖尿病的临床效果。方法:收治经饮食控制及单用胰岛素治疗效果欠佳的2型糖尿病患者62例,加用吡格列酮治疗4周和12周后,测定空腹血糖(FPG)、餐后2小时血糖(2hPG)及糖化血红蛋白(HbA1c),观察胰岛素用量的变化、低血糖发生率以及不良反应。结果:吡格列酮联合胰岛素治疗后4周及12周后FPG、2hPG和HbAlc较治疗前明显下降(P<0.01),每日胰岛素用量由(75±7)U减至(30±3)U(P<0.01),低血糖发生率显著下降,个别患者出现下肢轻度水肿不良反应。结论:饮食控制及单用胰岛素治疗效果欠佳的2型糖尿病患者加用吡格列酮治疗,可使血糖得到持续改善,并能减少全天胰岛素用量,改善胰岛素抵抗,并且不良反应轻微。%Objective:To explore the curative effect of pioglitazone combined with insulin in the treatment of type 2 diabetes. Methods:62 patients with type 2 diabetes who had poor effect treated with diet control and insulin alone were selected,who added pioglitazone treatment.At the forth week and twelfth week after the start of treatment,we measured fasting blood glucose(FPG),2 hours postprandial blood glucose(2hPG) and glycosylated hemoglobin(HbA1c),and observed the changes of insulin dosage, incidence of hypoglycemia and adverse reaction.Results:At the forth week and twelfth week after the start of treatment with pioglitazone combined with insulin,FPG,2hPG and HbAlc were significantly lower than that before treatment(P<0.01).Daily insulin dosage was reduced from 75 ± 7U to 30 ± 3U(P<0.01).The incidence of hypoglycemia was significantly decreased. Individual patients appeared adverse reaction of mild lower limb edema.Conclusion:For the patients with type 2 diabetes who had poor effect treated with diet control and insulin alone,the application of pioglitazone can get a lasting improvement of blood sugar, reduce the insulin dosage

  8. Effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributions in drug-naive subjects with type 2 diabetes.

    Science.gov (United States)

    Bi, Yan; Zhang, Bing; Xu, Wen; Yang, Huijie; Feng, Wenhuan; Li, Cuiliu; Tong, Guoyu; Li, Ming; Wang, Xin; Shen, Shanmei; Zhu, Bin; Weng, Jianping; Zhu, Dalong

    2014-10-01

    Ectopic accumulation of lipids in nonadipose tissues plays a primary role in the pathogenesis of type 2 diabetes mellitus (T2DM). This study was to examine the effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributions in T2DM. Thirty-three drug-naive T2DM patients (age 52.7 ± 1.7 years, HbA1c 8.7 ± 0.2 %, body mass index 24.5 ± 0.5 kg/m(2)) were randomized into exenatide, insulin, or pioglitazone for 6 months. Intrahepatic fat (IHF), visceral fat (VF), and subcutaneous fat (SF) were measured using proton nuclear magnetic resonance spectroscopy. Plasma tumor necrosis factor α (TNFα) and adiponectin were assayed by ELISA. HbA1c declined significantly in all three groups. Body weight, waist, and serum triglycerides decreased with exenatide. After interventions, IHF significantly reduced with three treatments (exenatide Δ = -68 %, insulin Δ = -58 %, pioglitazone Δ = -49 %). Exenatide reduced VF (Δ = -36 %) and SF (Δ = -13 %), and pioglitazone decreased VF (Δ = -30 %) with no impact on SF, whereas insulin had no impact on VF or SF. Levels of TNFα (exenatide/insulin/pioglitazone) decreased, and levels of adiponectin (exenatide/pioglitazone) increased. Analysis showed that ΔIHF correlated with ΔHbA1c and Δweight. Besides, ΔIHF correlated with Δtriglycerides and ΔTNFα, but the correlations fell short of significance after BMI adjustment. By linear regression analysis, ΔHbA1c alone explained 41.5 % of the variance of ΔIHF, and ΔHbA1c + Δweight explained 57.6 % of the variance. Liver fat content can be significantly reduced irrespective of using exenatide, insulin, and pioglitazone. Early glycaemic control plays an important role in slowing progression of fatty liver in T2DM.

  9. Soluble CD36 and risk markers of insulin resistance and atherosclerosis are elevated in polycystic ovary syndrome and significantly reduced during pioglitazone treatment

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Højlund, Kurt; Andersen, Marianne;

    2008-01-01

    OBJECTIVE: We investigated the relation between soluble CD36 (sCD36), risk markers of atherosclerosis and body composition, and glucose and lipid metabolism in polycystic ovary syndrome (PCOS). RESEARCH DESIGN AND METHODS: Thirty PCOS patients were randomized to 30 mg/day pioglitazone or placebo ...... improving insulin-stimulated glucose metabolism, further supporting the association between sCD36 and insulin resistance in PCOS. Udgivelsesdato: 2008-Feb...... for 16 weeks. Fourteen weight-matched healthy female subjects were included as control subjects. sCD36, oxidized LDL (oxLDL), high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, euglycemic-hyperinsulinemic clamps, and whole-body dual-energy X-ray absorptiometry scans were performed. RESULTS...

  10. Regulation of Diet-Induced Adipose Tissue and Systemic Inflammation by Salicylates and Pioglitazone

    Science.gov (United States)

    Kamei, Nozomu; Shimada, Takeshi; Liu, Libin; Moore, Kristin; Woo, Ju Rang; Shoelson, Steven E.; Lee, Jongsoon

    2013-01-01

    It is increasingly accepted that chronic inflammation participates in obesity-induced insulin resistance and type 2 diabetes (T2D). Salicylates and thiazolidinediones (TZDs) both have anti-inflammatory and anti-hyperglycemic properties. The present study compared the effects of these drugs on obesity-induced inflammation in adipose tissue (AT) and AT macrophages (ATMs), as well as the metabolic and immunological phenotypes of the animal models. Both drugs improved high fat diet (HFD)-induced insulin resistance. However, salicylates did not affect AT and ATM inflammation, whereas Pioglitazone improved these parameters. Interestingly, HFD and the drug treatments all modulated systemic inflammation as assessed by changes in circulating immune cell numbers and activation states. HFD increased the numbers of circulating white blood cells, neutrophils, and a pro-inflammatory monocyte subpopulation (Ly6Chi), whereas salicylates and Pioglitazone normalized these cell numbers. The drug treatments also decreased circulating lymphocyte numbers. These data suggest that obesity induces systemic inflammation by regulating circulating immune cell phenotypes and that anti-diabetic interventions suppress systemic inflammation by normalizing circulating immune phenotypes. PMID:24376593

  11. PPARγ agonist pioglitazone improves cerebellar dysfunction at pre-Aβ deposition stage in APPswe/PS1dE9 Alzheimer's disease model mice

    Energy Technology Data Exchange (ETDEWEB)

    Toba, Junya; Nikkuni, Miyu [Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Ishizeki, Masato [Laboratory for Neurophysiology, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Yoshii, Aya; Watamura, Naoto [Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Inoue, Takafumi [Laboratory for Neurophysiology, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Ohshima, Toshio, E-mail: ohshima@waseda.jp [Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan)

    2016-05-13

    Alzheimer's disease (AD) is one of the best known neurodegenerative diseases; it causes dementia and its pathological features include accumulation of amyloid β (Aβ) and neurofibrillary tangles (NFTs) in the brain. Elevated Cdk5 activity and CRMP2 phosphorylation have been reported in the brains of AD model mice at the early stage of the disease, but the significance thereof in human AD remains unelucidated. We have recently reported that Aβ accumulation in the cerebellum of AD model APPswe/PS1dE9 (APP/PS1) mice, and cerebellar dysfunctions, such as impairment of motor coordination ability and long-term depression (LTD) induction, at the pre-Aβ accumulation stage. In the present study, we found increased phosphorylation levels of CRMP2 as well as increased p35 protein levels in the cerebellum of APP/PS1 mice. Interestingly, we show that pioglitazone, an agonist of peroxisome proliferator-activated receptor γ, normalized the p35 protein and CRMP2 phosphorylation levels in the cerebellum. Impaired motor coordination ability and LTD in APP/PS1 mice were ameliorated by pioglitazone treatment at the pre-Aβ accumulation stage. These results suggest a correlation between CRMP2 phosphorylation and AD pathophysiology, and indicate the effectiveness of pioglitazone treatment at the pre-Aβ accumulation stage in AD model mice. -- Highlights: •Phosphorylation level of CRMP2 increased in the cerebellum of APP/PS1 mice. •p35 protein levels increased in the cerebellum of APP/PS1 mice. •Pioglitazone treatment improved cerebellar dysfunction of APP/PS1 mice.

  12. Usage of pioglitazone at Medanta, the Medicity

    Directory of Open Access Journals (Sweden)

    Ambrish Mithal

    2014-01-01

    Full Text Available Pioglitazone improves glycemic control by acting as an insulin sensitizer and is used in the management of Type 2 diabetes mellitus. Pioglitazone has recently been at the center of a controversy with regards to its safety. There is no clear consensus on how, when and in what dose the drug should be used in the management of diabetes. We have summarized our strategy on pioglitazone use in Type 2 diabetes in a large private tertiary care center - Medanta, the Medicity- which may help in generating further thought about positioning of this anti-diabetic molecule. We use pioglitazone as the fourth in the pecking order of oral anti-diabetic agents. We typically use pioglitazone in a dose of 15 mg/day. We avoid using pioglitazone with insulin. We do not use pioglitazone under following situations: In the presence of significant or proven cardiac disease, in patients who are struggling with their weight or need to lose weight, in patients at high risk for osteoporotic fractures, in patients with macular edema, in patients with pre-existing bladder cancer and would discontinue in case hematuria or any other symptom of bladder cancer develops. We continue to use the drug in patients well controlled on it without any evident side-effects or contraindications.

  13. Usage of pioglitazone at Medanta, the Medicity.

    Science.gov (United States)

    Mithal, Ambrish; Kaur, Parjeet; Bansal, Beena; Mishra, Sunil Kumar; Wasir, Jasjeet S; Jevalikar, Ganesh; Mahendru, Shama

    2014-01-01

    Pioglitazone improves glycemic control by acting as an insulin sensitizer and is used in the management of Type 2 diabetes mellitus. Pioglitazone has recently been at the center of a controversy with regards to its safety. There is no clear consensus on how, when and in what dose the drug should be used in the management of diabetes. We have summarized our strategy on pioglitazone use in Type 2 diabetes in a large private tertiary care center - Medanta, the Medicity- which may help in generating further thought about positioning of this anti-diabetic molecule. We use pioglitazone as the fourth in the pecking order of oral anti-diabetic agents. We typically use pioglitazone in a dose of 15 mg/day. We avoid using pioglitazone with insulin. We do not use pioglitazone under following situations: In the presence of significant or proven cardiac disease, in patients who are struggling with their weight or need to lose weight, in patients at high risk for osteoporotic fractures, in patients with macular edema, in patients with pre-existing bladder cancer and would discontinue in case hematuria or any other symptom of bladder cancer develops. We continue to use the drug in patients well controlled on it without any evident side-effects or contraindications.

  14. Efficacy of metformin and pioglitazone in treatment of type 2 diabetes%二甲双胍联合吡格列酮治疗2型糖尿病的疗效观察

    Institute of Scientific and Technical Information of China (English)

    吴茂林

    2013-01-01

    目的:探讨二甲双胍联合吡格列酮治疗2型糖尿病的临床疗效。方法入选的70例2型糖尿病患者,其中35例患者应用二甲双胍联合吡格列酮治疗,设为观察组,余35例2型糖尿病患者行二甲双胍治疗,设为对照组,应用统计学方法对比分析两组治疗6个月后的疗效及比较两组患者治疗前后空腹血糖(FBG)、餐后2h血糖(PBG)及糖化血红蛋白(HbA1C)的变化情况,同时注意并记录治疗过程中发生的不良反应情况。结果观察组治疗后的总有效率达94.3%,明显高于对照组治疗后的总有效率77.1%(P<0.05)。观察组与对照组患者治疗6个月后的FBG、2h PBG、HbA1C均较治疗前明显降低,且观察组患者的FBG、2h PBG、HbA1C均明显低于对照组(P<0.05)。结论二甲双胍联合吡格列酮治疗可以明显改善2型糖尿病的血糖和糖化血红蛋白水平,疗效确切,值得推广和应用。%Objective To investigate the clinical efficacy of metformin and pioglitazone in treatment of type 2 diabetes. Methods 70 cases type 2 diabetes, of which 35 patients were treated with metformin pioglitazone treatment, the establishment of the observation group, another 35 cases of type 2 diabetic patients were treated with metforminas as the control group, after treatment 6 months, fasting blood glucose (FBG), 2h postprandial blood glucose (PBG) and glycosylated hemoglobin (HbA1C) changes and adverse reactions were compared between two groups. Results After treatment, the total effective rate of observation group was 94.3%, was significantly higher than the control group 77.1%(P < 0.05). The FBG, 2h PBG, HbA1C of observation group and control group treated 6 months was significantly lower than before treatment, and the observation group was significantly lower than the control group,the difference was significant (P < 0.05). Conclusion Metformin and pioglitazone can significantly improve blood sugar and

  15. Beneficial effects of pioglitazone on retardation of persistent atrial fibrillation progression in diabetes mellitus patients.

    Science.gov (United States)

    Liu, Bing; Wang, Jiancheng; Wang, Guoxing

    2014-01-01

    This study aimed to explore the effects of pioglitazone treatment on progression from persistent atrial fibrillation (AF) to permanent atrial fibrillation in diabetes mellitus (DM) patients and to investigate the possible mechanisms involved in those effects.A total of 146 diabetes mellitus (DM) patients with firstly identified persistent AF were selected. Seventy patients were randomized into the pioglitazone (30 mg/day) group and 76 into the placebo group. Pro-collagen type I carboxyterminal peptide (PICP), advanced glycation end products (AGEs), and angiotensin II were assayed and left atrial diameter (LA diameter) was measured at the first presence of persistent AF, and at 6 and 14 months of follow-up. The time point of identification of permanent AF and the incidence of permanent AF in the patients were all recorded.Thirty-seven (49%) of the 76 patients in the placebo group and 21 (30%) of the 70 patients in the pioglitazone group progressed to permanent AF (P = 0.028). No significant differences existed in the follow-up time (20.5 ± 3.97 months for pioglitazone group versus 20.9 ± 4.14 months for placebo group) between the two groups (P = 0.535). In the pioglitazone group, no significant change was found in angiotensin II level. The PICP level did not change significantly at 6-months of follow-up, but decreased significantly at 14-months of follow-up (P = 0.032). The AGE (P = 0.037 at 6-month follow-up, P pioglitazone treatment may decrease the incidence of permanent AF in DM patients with persistent AF, which may be associated with the suppressing effect of pioglitazone on AGEs.

  16. Pioglitazone Randomised Italian Study on Metabolic Syndrome (PRISMA): effect of pioglitazone with metformin on HDL-C levels in Type 2 diabetic patients.

    Science.gov (United States)

    Genovese, S; Passaro, A; Brunetti, P; Comaschi, M; Cucinotta, D; Egan, C G; Chinea, B; Bravi, F; Di Pietro, C

    2013-09-01

    Previous evidence indicates that pioglitazone may improve dyslipidemia in patients with Type 2 diabetes mellitus (T2DM). The primary objective of this study was to evaluate the effect of either pioglitazone or placebo with metformin on levels of serum HDL cholesterol (HDL-C) in patients with T2DM. A secondary objective evaluated changes in metabolic syndrome (MS)-specific parameters. This multicenter, double-blind, randomized study was performed in patients with T2DM treated with metformin and hemoglobin A1c (HbA1c) levels between 6-8%, central obesity and reduced HDL-C. MS was evaluated from global changes in parameter values and expressed as a single factorial score following multivariate analysis of each parameter. 213 patients (110 in the pioglitazone group and 103 in the placebo group) were available for intention-to-treat analysis. Pioglitazone-treated patients showed a significant increase in HDL-C compared to placebo group (6.3 mg/dl vs 3.0 mg/dl; pHDL-C and the reduction of insulin resistance and atherogenic LDL subfractions), support findings from the PROactive trial, where pioglitazone showed pleiotropic effects and reduced death, fatal myocardial infarction (MI) and non-fatal MI in T2DM patients with MS. Furthermore, medication used in this study showed good tolerability.

  17. 吡格列酮对初诊2型糖尿病患者胰岛素强化治疗长期缓解的影响%Effect of pioglitazone on long-term remission in newly diagnosed type 2 diabetic patients with intensive insulin treatment

    Institute of Scientific and Technical Information of China (English)

    胡文; 刘芳; 俞伟男

    2011-01-01

    Aim To observe the effect of pioglitazone on long-term remission in newly diagnosed type 2 diabetic patients with intensive insulin treatment. Methods 67 patients with newly diagnose type 2 diabetes were randomly divided into two groups: intensive insulin therapy group (Ins group) and insulin + pioglitazone group (Ins + PIo group) .4 months after treatment were detected and time of intensive insulin was recorded,blood glucose,blood lipids,glycated hemoglobin,insulin,C peptide levels. Serum concentrations before and after the therapy was measured by ELASA method. Results Insulin pump treatment time blood glucose for standardizing was shorter in Ins + PIo group than that in Ins grop (P < 0.05). 3 months later remission rate (61.7%) in Ins + PIo group was higher than that in Ins group. And fasting plasma glucose,glycosylated hemoglobin,HOMA-IR in Ins + Pio group remission were lower than those in Ins group remission,while HOMA-β was higher (P < 0.05). 3 months later serum Visfatin changed greatly in Ins + PIo group before and after treatment (P < 0.05). Concultion Pioglitazone can reduce the insulin pump treatment time in newly diagnosed type 2 diabetic patients and increase opportunities for long-term remission. And the effect is related to changes in Visfatin concentration.%目的 观察吡格列酮对初诊2型糖尿病患者胰岛素强化治疗长期缓解的影响.方法 选择67名初诊2型糖尿病患者随机分成2组:胰岛素强化治疗组(Ins组)和胰岛素强化+吡格列酮治疗组(Ins+Pio组).治疗4个月后:(1)记录胰岛素强化所用时间.(2)检测血糖、血脂、糖化血红蛋白、胰岛素、C肽水平.(3)ELASA法测定血清内脂素(Visfatin)的变化.结果 (1)Ins+Pio组血糖达标所需胰岛素强化治疗时间较Ins组短(P<0.05).(2)随访3月后Ins+Pio组缓解率高(P<0.05);Ins+Pio组缓解者Visfatin治疗前后变化大(P<0.05).结论 吡格列酮可以缩短初诊2型糖尿病患者胰岛素强化治疗时间,增

  18. 非诺贝特联合吡格列酮治疗青少年代谢综合征的分析%Fenofibrate combined with pioglitazone for the treatment of metabolic syndrome in adolescences at the preliminary diagnosis

    Institute of Scientific and Technical Information of China (English)

    范晓琳; 苏如婷; 韩晓骏

    2009-01-01

    目的 探讨非诺贝特联合吡格列酮在初诊青少年代谢综合征(MS)治疗中的近期及远期疗效.方法 按国际糖尿病联盟(IDF)关于MS防治建议诊断标准,选择含高血脂、高血糖组分的初诊患者42例,应用非诺贝特联合吡格列酮治疗半年,随访甘油三酯、高密度脂蛋白、空腹血糖、餐后2 h血糖、糖化血红蛋白、腰围、体重指数.结果 血脂、血糖恢复正常患者情况:治疗半年后占90%(38/42),停药半年后占83%(35/42),停药1年后占76%(32/42),漏服药率<2%.结论 肥胖和胰岛素抵抗是MS的根本危险因素,改善胰岛素敏感性是MS综合治疗措施的基础.非诺贝特联合吡格列酮治疗初诊青少年MS依从性好,近期及远期疗效好,值得推荐为初诊的初始治疗方案.%Objective To investigate the short and long term curative effect of fenofibrate combined with pioglitazone for the treatment of metabolic syndrome(MS) in adolescences at the preliminary diagnosis.Methods Forty-two patients with hyperlipemia and hyperglycemia at the preliminary diagnosis according to the diagnostic criteria of IDF.Treat with fenofibrate and pioglitazone for 6 months.Follow-up the triglyceride,high density lipoprotein,fasting plasma glucose (FPG),postchallenge plasma glucose two hours(PPG2 h),HbA1c,waist,body mass index(BMI).Results The blood fat and glucose of 90% (38/42) patients return to normal 6 months after treatment,83% (35/42) patients 6 months after drug withdrawal.76% (32/42) patients 12 months after drug withdrawal,missed dose (less than 2%).Conclusions Obesity and insulin resistance(IR) are basic risks factors of MS.Ameliorate the insulin sensitivity is the basic therapeutic measure of MS.The dependence,the short-term and long-term curative effect of fenofibrate combined with pioglitazone for the treatment of MS in adolescences at the preliminary diagnosis are fine.It is worth recommending.

  19. Protective effect of pioglitazone on kidney injury in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-Hui Peng; Pei-Yu Liang; Shan-Ji Ou; Xiong-Bing Zu

    2014-01-01

    Objective:To investigate the protective effect of pioglitazone on kidney injury in diabetic rat model and its mechanisms.Methods:Forty healthySpragueDawley rats were selected and randomly divided into five groups, with8 rats in each group.GroupA served as control group and were administered with sterile citrate buffer(i.p.) as placebo.GroupsB,C,D andE rats were injected(i.p.) with streptozotocin to induce typeⅠdiabetes.Diabetic rats inGroupB were intragastrically administered with sterile saline solution alone.GroupsC,D andE rats were intragastrically given pioglitazone hydrochloride suspension at doses of10,20,30 mg/kg per day, respectively.After eight weeks of treatment, all rats were anesthetized and blood was withdrawn from the abdominal aortic for detection of hemoglobinA1c, serum creatinine(SCr) and blood urea nitrogen(BUN) levels.Rats were then sacrificed and the left kidney was excised for calculation of kidney hypertrophy index(KHI), observation of renal pathological changes using light microscope and electron microscope.Mean glomerular cross-sectional areas(MGA), mean glomerular volume (MGV), glomerular basement membrane thickness and foot process fusion ratio were calculated. RT-PCR was employed for detection of podocalyxin(PCX) protein expression.Results:Results showed that levels of hemoglobinA1c,BUN,SCr inGroupsB,C,D andE rats were significantly higher than those inGroupA(P<0.05), whileBUN andSCr levels in rats ofGroupsC,D andE were significantly lower than those inGroupB(P<0.05).KHI,MGA andMGV levels were significantly higher inGroupsB,C,D andE rats than those inGroupA(P<0.05);KHI andMGA levels inGroup B rats were significantly higher than those inGroupsC,D andE(P<0.05) andMGV inGroups D andE was significantly lower than that inGroupsB andC(P<0.05).Histology study showed normal glomerulus structure, morphology, volume, endothelial cells and mesangial cells as well as clear glomerular capillary inGroupA rats.Renal mesangial matrix proliferation and

  20. Effect of pioglitazone on glucose metabolism and luteinizing hormone secretion in women with polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Hermann, Anne Pernille; Andersen, Marianne

    2006-01-01

    OBJECTIVE: To thoroughly examine the mechanisms for insulin resistance in polycystic ovary syndrome (PCOS) and to evaluate the effects of pioglitazone treatment on insulin resistance, beta-cell function, LH secretion, and glucose metabolism. DESIGN: Randomized, blinded, placebo-controlled study....... SETTING: Outpatient clinic, at a university hospital in Denmark. PATIENT(S): Thirty obese women with PCOS and 14 weight-matched healthy females. INTERVENTION(S): Sixteen weeks of blinded treatment with pioglitazone (30 mg/d) or placebo. MAIN OUTCOME MEASURE(S): Fasting blood samples, 24-hour 20-minute...

  1. Impact of alogliptin and pioglitazone on lipid metabolism in islets of prediabetic and diabetic Zucker Diabetic Fatty rats.

    Science.gov (United States)

    Cai, Ying; Lydic, Todd A; Turkette, Thomas; Reid, Gavin E; Olson, L Karl

    2015-05-01

    Prolonged exposure of pancreatic beta (β) cells to elevated glucose and free fatty acids (FFA) as occurs in type 2 diabetes results in loss of β cell function and survival. In Zucker Diabetic Fatty (ZDF) rats, β cell failure is associated with increased triacylglyceride (TAG) synthesis and disruption of the glycerolipid/FFA (GL/FFA) cycle, a critical arm of glucose-stimulated insulin secretion (GSIS). The aim of this study was to determine the impact of activation of PPARγ and increased incretin action via dipeptidyl-peptidase inhibition using pioglitazone and/or alogliptin, respectively, on islet lipid metabolism in prediabetic and diabetic ZDF rats. Transition of control prediabetic ZDF rats to diabetes was associated with reduced plasma insulin levels, reduced islet insulin content and GSIS, reduced stearoyl-CoA desaturase 2 (SCD 2) expression, and increased islet TAG, diacylglyceride (DAG) and ceramides species containing saturated FA. Treatment of prediabetic ZDF rats with a combination of pioglitazone and alogliptin, but not individually, prevented the transition to diabetes and was associated with marked lowering of islet TAG and DAG levels. Pioglitazone and alogliptin, however, did not restore SCD2 expression, the degree of FA saturation in TAG, DAG or ceramides, islet insulin content, or lower ceramide levels. These findings are consistent with activation of PPARγ and increased incretin action working in concert to restore GL/FFA cycle in β cells of ZDF rats. Restoration of the GL/FFA cycle without correcting islet FA desaturation, production of islet ceramides, and/or insulin sensitivity, however, may place these islets at risk for β cell failure.

  2. Pioglitazone

    Science.gov (United States)

    ... following: atorvastatin (Lipitor, in Caduet), gemfibrozil (Lopid), hormonal contraceptives (birth control pills, patches, rings, implants, and injections), insulin or other medications to treat ...

  3. Investigation of the antibacterial activity of pioglitazone

    Directory of Open Access Journals (Sweden)

    Alzoubi KH

    2011-09-01

    Full Text Available Majed M Masadeh1, Nizar M Mhaidat2, Sayer I Al-Azzam2, Karem H Alzoubi21Department of Pharmaceutical Technology; 2Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, JordanPurpose: To evaluate the antibacterial potential of pioglitazone, a member of the thiazolidinediones class of drugs, against Gram-positive (Streptococcus pneumoniae and Gram-negative (Escherichia coli and Klebsiella pneumoniae bacteria.Methods: Susceptibility testing was done using the antibiotic disk diffusion method and the minimal inhibitory concentration (MIC of pioglitazone was measured according to the broth micro incubation standard method.Results: Pioglitazone induced a dose-dependent antibacterial activity in which the optimal concentration was 80 µM. Furthermore, results indicated that while E. coli was sensitive (MIC = 31.25 ± 3.87 mg/L to pioglitazone-induced cytotoxicity, S. pneumoniae and K. pneumoniae were resistant (MIC = 62.5 ± 3.77 mg/L and MIC = 62.5 ± 4.14 mg/L, respectively. Moreover, pretreatment of bacteria with a suboptimal concentration of pioglitazone (40 µM before adding amoxicillin, cephalexin, co-trimoxazole, or ciprofloxacin enhanced the antibacterial activity of all agents except co-trimoxazole. This enhancing effect was particularly seen against K. pneumoniae.Conclusion: These results indicate the possibility of a new and potentially important pioglitazone effect and the authors’ ongoing studies aim to illustrate the mechanism(s by which this antibacterial effect is induced.Keywords: pioglitazone, susceptibility testing, antibiotics, diabetes 

  4. Low dose pioglitazone does not affect bone formation and resorption markers or bone mineral density in streptozocin-induced diabetic rats.

    Science.gov (United States)

    Tsirella, E; Mavrakanas, T; Rager, O; Tsartsalis, S; Kallaras, K; Kokkas, B; Mironidou-Tzouveleki, M

    2012-04-01

    Our study aims to investigate the effect of a low-dose pioglitazone regimen on bone mineral density and bone formation-resorption markers in control and diabetic rats. Wistar rats were divided into 4 groups: non-diabetic controls, control rats receiving pioglitazone (3 mg/kg), streptozocin-treated diabetic rats (50 mg/kg), diabetic rats treated with pioglitazone (3 mg/kg). The duration of the experiment was 8 weeks. Diabetes in our rats was associated with weight loss, increased urinary calcium excretion and reduced plasma osteocalcin levels. Diabetes mellitus did not affect bone mineral density. Pioglitazone administration had no impact on bone formation and resorption markers levels and did not modify bone mineral density in the four studied groups. Pioglitazone at the 3 mg/kg dose was not associated with significant skeletal complications in our experimental model.

  5. Randomized,double-blind,double-dummy,controlled clinical trial of pioglitazone /metformin in the treatment of type 2 diabetes%吡格列酮二甲双胍片治疗2型糖尿病的多中心随机双盲平行对照临床试验

    Institute of Scientific and Technical Information of China (English)

    胡红琳; 王长江; 张木勋; 阎胜利; 刘俊江; 朱旅云; 何勇; 高雅

    2009-01-01

    Objective To evaluate the efficacy and safety of pioglitazone /metformin hydrochloride in the treatment of type 2 diabetes mellitus patients. Methods A randomized, double-blind, metformin and pioglitazone hydrochloride-controlled, and multicenter clinical trial was conducted. A total of 240 patients with type 2 diabetes mellitus were enrolled in this study, in which 120 patients received pioglitazone/ metformin, and 120 patients received metformin and pioglitazone. Result Comparing to the baseline, the fasting blood glucose ( FBG) , 2 h postprandial blood glucose (P2hBG) and HbAlc levels in tow groups were significantly reduced after 16-week treatment ( P < 0. 01 ) . In pioglitazone/metformin group, the mean reductions of FBG, P2hBG and HbAlc levels were (1. 92 ± 1. 77 ) mmol · L~(-1), ( 2. 49 ± 3. 13 ) mmol · L~(-1), (1. 27 ± 1. 45 ) % respectively. In metformin and pioglitazone group, the mean reductions of FBG, P2hBG and HbAlc levels were (2. 24 ±2. 11) mmol · L~(-1), (2. 89 ± 3. 71) mmol · L~(-1), ( 1. 49 ± 1. 52)% respectively. The differences in reductions of FBG, P2hBG and HbAlc level between the groups were not statistically significant. The incidence of adverse drug reaction in two groups was similar (10% vs 12%). Conclusion This result provides an efficacy and safety of pioglitazone /metformin in the treatment of type 2 diabetes mellitus.%目的 以盐酸二甲双胍和盐酸吡格列酮(均降糖药)为对照,评价吡格列酮二甲双胍片治疗2型糖尿病的疗效和安全性.方法 用多中心随机双盲双模拟阳性平行对照的试验设计,观察240例2型糖尿病病人,分为吡格列酮二甲双胍片组(试验组)和盐酸二甲双胍、盐酸吡格列酮组(对照组).结果 用药16周后,与基础值相比,试验组空腹血糖(FBG)、餐后2 h血糖(P2hBG)、糖化血红蛋白(HbAlC)分别下降(1.92±1.77)mmol·L~(-1),(2.49±3.13)mmol·L~(-1),(1.27±1.45)%;对照组,FBG、PBG、HbA1c分别下降(2.24±2.11)mmol·L~(-1

  6. Coefficient of beta-cell failure in patients with type 2 diabetes treated with pioglitazone or acarbose.

    Science.gov (United States)

    Göke, B; Lübben, G; Bates, P C

    2004-02-01

    A new method of assessing the coefficient of failure of pancreatic beta-cells from any index of glycaemia has been proposed. This method of analysis has been used to assess data on HbA1c and fasting glucose concentrations from a randomised study comparing pioglitazone with acarbose. Patients were treated for 26 weeks with either pioglitazone 45 mg once daily or acarbose 300 mg/day as 3 equal doses. Plasma HbA1c concentration was measured every two months and fasting glucose was measured monthly. The coefficient of failure was determined for each patient from the slope of the least squares regression line over time. The coefficient of failure from HbA1c was - 2.65 +/- 2.13 %/year with pioglitazone and - 1.25 +/- 3.11 %/year with acarbose, indicating improved beta-cell function in each case. The coefficient of failure was improved to a significantly greater extent with pioglitazone ( P Coefficient of failure from fasting blood glucose also showed a greater improvement with pioglitazone (- 53.1 +/- 95.0 mg/dl/year) than with acarbose (- 29.9 +/- 142.5 mg/dl/year; p = 0.049). The coefficient of failure showed a significantly greater improvement of beta-cell function with pioglitazone than with acarbose during 26 weeks of treatment.

  7. Pioglitazone ameliorates nonalcoholic steatohepatitis by down-regulating hepatic nuclear factor-kappa B and cyclooxygenases-2 expression in rats

    Institute of Scientific and Technical Information of China (English)

    ZHAO Jia-sheng; ZHU Feng-shang; LIU Su; YANG Chang-qing; CHEN Xi-mei

    2012-01-01

    Background Pioglitazone is effective in nonalcoholic steatohepatitis (NASH),but the mechanisms of action are not completely understood.This study was designed to investigate the effects of pioglitazone on hepatic nuclear factor-kappa B (NF-κB) and cyclooxygenases-2 (COX-2) expression in NASH rats.Methods Thirty Sprague-Dawley male rats were randomly assigned to a control group (n=10),NASH group (n=10),and pioglitazone treatment group (n=10).Liver tissues were processed for histology by hematoxylin & eosin and Masson stained.Serum alanine aminotransferase (ALT),cholesterol,triglyceride,fasting blood glucose (FBG),fasting insulin (FINS) levels and biochemical parameters of antioxidant enzyme activities,tumor necrosis factor alpha (TNF-α),prostaglandin E2 (PGE2) levels in serum and liver were measured.The mRNA and protein expression of peroxisome proliferator-activated receptor gamma (PPARy),NF-κB and COX-2 were determined by real-time polymerase chain reaction,Westem blotting and immunohistochemistry.One-way analysis of variance (ANOVA) and Wilcoxon's signed-rank test was used for the statistical analysis.Results There were severe steatosis,moderate inflammatory cellular infiltration and fibrosis in NASH rats.After pioglitazone treatment,steatosis,inflammation and fibrosis were significantly improved compared with the NASH group(X2=20.40,P <0.001; )X2=20.17,P <0.001; X2=13.98,P=0.002).Serum ALT,cholesterol,triglyceride,FBG,FINS levelswere significantly elevated in the NASH group (P <0.05).In the NASH group,total anti-oxidation competence (T-AOC),superoxide dismutase (SOD),catalase (CAT),glutathione peroxidase (GSH-PX) and malondialdehyde (MDA) levels inserum and liver were conspicuous disordered than those parameters in the control group.Meanwhile,TNF-α and PGE2levels in serum and liver were significantly increased compared with the control group.Immunohistochemistry showedNF-KB and COX-2 expression in liver was significantly elevated.However,PPARy level

  8. Long-term rates of mitochondrial protein synthesis are increased in mouse skeletal muscle with high fat feeding regardless of insulin sensitizing treatment.

    Science.gov (United States)

    Newsom, Sean A; Miller, Benjamin F; Hamilton, Karyn L; Ehrlicher, Sarah E; Stierwalt, Harrison D; Robinson, Matthew M

    2017-07-11

    Skeletal muscle mitochondrial protein synthesis is regulated in part by insulin. The development of insulin resistance with diet-induced obesity may therefore contribute to impairments to protein synthesis and decreased mitochondrial respiration. Yet, the impact of diet-induced obesity and insulin resistance on mitochondrial energetics is controversial with reports varying from decreases to increases in mitochondrial respiration. We investigated the impact of changes in insulin sensitivity on long-term rates of mitochondrial protein synthesis as a mechanism for changes to mitochondrial respiration in skeletal muscle. Insulin resistance was induced in C57BL/6J mice using 4 weeks of high-fat compared with low-fat diet. For 8 additional weeks, diets were enriched in pioglitazone to restore insulin sensitivity as compared with non-enriched control low-fat or high-fat diet. Skeletal muscle mitochondrial protein synthesis was measured using deuterium oxide labeling during weeks 10 to 12. High-resolution respirometry was performed using palmitoyl-L-carnitine, glutamate+malate and glutamate+malate+succinate as substrates for mitochondria isolated from quadriceps. Mitochondrial protein synthesis and palmitoyl-L-carnitine oxidation were increased in mice consuming high-fat diet, regardless of differences in insulin sensitivity with pioglitazone treatment. There was no effect of diet or pioglitazone treatment on ADP-stimulated respiration or H2O2 emission using glutamate+malate or glutamate+malate+succinate. The results demonstrate no impairments to mitochondrial protein synthesis or respiration following induction of insulin resistance. Instead, mitochondrial protein synthesis was increased with high-fat diet and may contribute to remodeling of the mitochondria to increase lipid oxidation capacity. Mitochondrial adaptations with high-fat diet appear driven by nutrient availability, not intrinsic defects that contribute to insulin resistance. Copyright © 2017, American

  9. 二甲双胍与吡格列酮联合治疗2型糖尿病的临床观察%Clinical Observation of Metformin and Pioglitazone in the Treatment of Type 2 Diabetes

    Institute of Scientific and Technical Information of China (English)

    饶鼎鼎

    2016-01-01

    Objective: To explore the clinical effect of metformin and pioglitazone combination therapy in the treatment of type 2 diabetes. Methods: A total of60 cases of type 2 diabetic patients in Jinxi County TCM Hospital of Fuzhou City of Jiangxi Province accepted treatment from March 2015 to March 2016 were randomly chosen and divided into treatment group and control group, with 30 cases in each. The control group was treated with metformin, and the treatment group accepted metformin and pioglitazone. The treatment effects were compared between the two groups by body mass index (BMI), glycosylated hemoglobin (Hb A1c), glycated albumin (GSP), fasting blood glucose (FBG), postprandial 2 hours blood glucose (2h PBG), glucagon hormone like peptide-1 (GLP-1), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) to improve the situation and adverse reactions.Results: Treatment group cure rate is 80%, with the total efficiency of 93.33%; and the number of cases of adverse reactions in 2 cases. The control group cure rate is 53.33%, with 73.4% efficiency; and the number of cases of adverse reactions in 6 cases. The results showed, the clinical effects of the treatment group is superior to control group, since the body mass index, glycated hemoglobin, glycated albumin, fasting blood glucose, postprandial 2 Hour blood glucose, glucagon like peptide, triglyceride, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol significantly better than that of the control group, and adverse reaction cases was fewer than that of the control group (P<0.05).Conclusions: Metformin and pioglitazone combination therapy in patients with type 2 diabetes mellitus has good curative effect, can better improve the patient body mass index, glycated hemoglobin, glycated albumin, fasting blood glucose, 2-hour postprandial blood glucose, glucagon like peptide, triglyceride, total

  10. Double-blind, randomized, multicentre, and active comparator controlled investigation of the effect of Pioglitazone, Metformin, and the combination of both on cardiovascular risk in patients with type 2 diabetes receiving stable basal insulin therapy: the PIOCOMB study

    Directory of Open Access Journals (Sweden)

    Kleine Iris

    2011-07-01

    Full Text Available Abstract Background We analyzed specific effects of an add-on therapy with pioglitazone compared to metformin and their combination in patients with basal insulin treatment on biomarkers of CV risk. Methods In this double-blind, randomized, multicentre, active comparator controlled trial, 121 patients with type 2 diabetes were enrolled. Inclusions: treatment with basal insulin, HbA1C 6.5% - 8.5%, age 30 - 75 years. After glargine therapy over 2 weeks for titration towards FBG ≤ 7.8 mmol/L, patients received either (A bid 850 mg metformin (n = 42, (B bid 15 mg pioglitazone (n = 40, or (C 30 mg pioglitazone plus 1.7 g metformin (n = 39 over 6 months. Matrix Metal Proteinase 9 (MMP-9 was primary objective, together with biomarkers of CV risk. Results Pioglitazone (B reduced MMP-9 versus baseline by 54.1 + 187.1 ng/mL, with metformin (A it was increased by 49.6 + 336.2 ng/mL (p = 0.0345; B vs. A, and with the combination of both (C it was decreased by 67.8 + 231.4 ng/mL (A vs. C: p = 0.0416; B vs. C: p = 0.8695. After logarithmic transformation due to high variances the exploratory results showed significance for A vs. B (p = 0.0043 and for A vs. C (p = 0.0289. Insulin dosage was reduced by 7.3 units in group B (p 1C was only significantly decreased in the combination group. No significant effects were observed for NFkB and PGFα. peripheral edema were seen in 11.9% vs. 40.0% vs. 20.5%, and weight change was -0.7 kg vs. +4.3 kg vs. +2.7 kg (A vs. B vs. C. Conclusions Addition of pioglitazone but not of metformin reduces MMP-9, hs-CRP and increased insulin sensitivity and adiponectin in this study. The combination of both had no additional effect on inflammation. Pioglitazone is suggested to be a rational add-on therapy to basal insulin in patients with high CV risk.

  11. 盐酸吡格列酮治疗单用胰岛素血糖控制不佳糖尿病效果探讨%Effect Discussion on the Pioglitazone Hydrochloride in Treatment of Single-use Insulin in Poor Glycemic Control Diabetes

    Institute of Scientific and Technical Information of China (English)

    陈振领

    2015-01-01

    目的 探讨盐酸吡格列酮治疗单用胰岛素血糖控制不佳糖尿病患者临床应用效果.方法82例患者均保持原有胰岛素使用剂量不变并加用盐酸吡格列酮治疗,记录其治疗前后空腹血糖变化情况,将所得资料经专业分析后获得结论.结果 82例单用胰岛素血糖控制不佳糖尿病患者经盐酸吡格列酮治疗后,其空腹血糖较之前降低,对比结果具有统计学意义(P<0.05).结论 对单用胰岛素血糖控制不佳的糖尿病患者给予盐酸吡格列酮联合治疗后可获得满意的血糖控制效果,有利于保障其生活质量及生命安全.%Objective To explore the clinical application effect of pioglitazone hydrochloride in the treatment of insulin alone in poor glycemic control in diabetic patients. Methods 82 patients were using the same dose of insulin and treated with pioglitazone, recorded the changes of fasting blood-glucose before and after the treatment, the data obtained were given for professional analysis and then drew the Conclusion . Results 82 patients with insulin alone in poor glycemic control diabetes after treatment with pioglitazone, the fasting blood-glucose was significantly lower than before, the Results were statistically significant (P < 0.05). Conclusion If give the single-use insulin in poor glucose control diabetic patients pioglitazone hydrochloride for combined treatment , satisfactory blood glucose control effect will be obtained, and that is conducive to the protection of the quality of life and life safety.

  12. Risk of bladder cancer among patients with diabetes treated with a 15 mg pioglitazone dose in Korea: a multi-center retrospective cohort study.

    Science.gov (United States)

    Jin, Sang-Man; Song, Sun Ok; Jung, Chang Hee; Chang, Jin-Sun; Suh, Sunghwan; Kang, Seung Min; Jung, Inkyung; Park, Cheol-Young; Kim, Jae Hyeon; Cho, Jae Hyoung; Lee, Byung-Wan

    2014-02-01

    It has not yet been determined whether chronic exposure to relatively low doses of pioglitazone increases risk of bladder cancer. We aimed to assess the risk of bladder cancer associated with pioglitazone in Korean patients. This was a retrospective cohort study of diabetic patients who had ≥ 2 clinic visits between November 2005 and June 2011 at one of four tertiary referral hospitals in Korea. A prevalent case-control analysis nested within the cohort was conducted to further adjust confounders. A total of 101,953 control patients and 11,240 pioglitazone-treated patients were included, in which there were 237 and 30 cases of incidental bladder cancer (64.9 and 54.9 per 100,000 person-years; age, sex-adjusted HR 1.135, 95% confidence interval [CI] 0.769-1.677), respectively. In the prevalent case-control analysis nested within the cohort, use of pioglitazone for a duration of > 6 months, but not ever use of pioglitazone, was associated with an increased rate of bladder cancer as compared to never use of pioglitazone. In conclusion, we failed to exclude the possible association between use of pioglitazone for a duration of > 6 months and bladder cancer.

  13. Comparison of metabolic profile and adiponectin level with pioglitazone versus voglibose in patients with type-2 diabetes mellitus associated with metabolic syndrome.

    Science.gov (United States)

    Fujitaka, Keisuke; Otani, Hajime; Jo, Fusakazu; Jo, Hiromi; Nomura, Emiko; Iwasaki, Masayoshi; Nishikawa, Mitsushige; Iwasaka, Toshiji

    2011-01-01

    Type 2 diabetes mellitus (T2DM) associated with metabolic syndrome (MetS) represents a high risk of cardiovascular disease. We compared the effect of early intervention with pioglitazone versus voglibose on physical and metabolic profiles and serum adiponectin level in patients with T2DM associated with MetS. Sixty patients who were diagnosed for the first time as T2DM associated with MetS were analyzed for insulin sensitivity, lipid profile, serum adiponectin and systemic inflammation. Those patients were randomly assigned to oral pioglitazone group (n = 30) or voglibose group (n = 30) in addition to conventional diet and exercise training. Body mass index and waist circumference did not change in the pioglitazone group, whereas these physical parameters significantly decreased in the voglibose group during a 6-month follow-up period. However, glycosylated hemoglobin, fasting plasma glucose, and HOMA-IR more significantly decreased in the pioglitazone group. The level of serum adiponectin especially high-molecular weight adiponectin markedly increased in the pioglitazone group. Moreover, high sensitive CRP significantly decreased only in the pioglitazone group. These results suggest that voglibose is superior in improving obesity, while pioglitazone is superior in ameliorating insulin sensitivity and increasing serum adiponectin in patients with an early stage of T2DM associated with MetS.

  14. Effects of PPARg agonist pioglitazone on rat hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Guang-Jin Yuan; Ming-Liang Zhang; Zuo-Jiong Gong

    2004-01-01

    AIM: To investigate effects of pioglitazone on rat hepatic fibrosis and to explore its mechanism.METHODS: Rat hepatic fibrosis was induced by carbon tet:achloride (CCl4). Forty Sprague-Dawley rats were divided randomly into 4 groups: control, model, and two treatment (PⅠ, PⅡ) groups. Except for rats in control group, all rats were given subcutaneous injection of 400 mL/L CCl4, twice a wk for 8 wk. Rats in PⅠ and PⅡ groups were also treated with pioglitazone of 3 mg/kg, daily via gastrogavage beginning on the 1st day and at the end of the 2nd week,administration of CCl4 respectively. Liver functions (ALT,AST), serum fibrotic markers (HA, LN, PCⅢ) and hepatic hydroxyproline (HP) concentration were determined respectively. Histochemical staining of formalin-fixed liver sections with HE, Masson-Trichrome, and immunohistochemical staining for α-smooth muscle actin (α-SMA) were performed.Modified Knodell and Chevallier semi-quantitative scoring system (SSS) was used to evaluate necroinflammatory activity and fibrosis degree.RESULTS: Compared with model group, pioglitazone significantly reduced the serum levels of ALT, AST, HA, LN and PCⅢ (P<0.05 or <0.01). The HP concentrations in PⅠ (210.90±24.07 μg/g), and PⅡ (257.36±30.55 μg/g) groups were also lower than those in model group (317.80±36.44 μg/g) (P<0.01). Histologic examination showed that PⅠ and PⅡ groups had milder hepatocellular degeneration, necrosis and infiltration of inflammatory cells, and thinner or less fibrotic septa than did model group. The scores for necroinflammation in PⅠ (2.80±1.03), and PⅡ (3.00±1.05) groups were significantly reduced as compared with model group (4.88±2.30) (P<0.05 or <0.01); the fibrosis scores in PⅠ (3.40±1.65), and PⅡ (4.60±1.35) groups were also markedly lower than those in model group (7.00±3.21)(P<0.05 or <0.01). Immunohistochemical staining showed that expression of α-SMA in PⅠ and PⅡ groups was ameliorated

  15. Comparison clinical and metabolic effects of metformin and pioglitazone in polycystic ovary syndrome

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    Karoon Shahebrahimi

    2016-01-01

    Full Text Available Introduction: Polycystic ovary syndrome (PCOS is one of the most common endocrine disorders in women. PCOS comprises a broad spectrum of anomalies, including hyperandrogenism, chronic anovulation, obesity, and infertility. Insulin resistance and its compensatory hyperinsulinemia play a key role in the pathogenicity of PCOS. This study compares the effects of 2 types of insulin sensitizer drugs, metformin and pioglitazone, on clinical, metabolic, and endocrine characteristics of women with PCOS. Methods: In this randomized clinical trial, 56 women with PCOS (ages 20–49 years were treated orally with either metformin (500 mg 3 times daily or pioglitazone (30 mg daily for 3 months. Clinical (body weight, blood pressure [BP], and body mass index and laboratory indices (fasting blood sugar [FBS], serum triglyceride [TG], cholesterol, low-density lipoprotein, high-density lipoprotein, insulin, testosterone, and dehydroepiandrosterone [DHEA] were measured before and after therapy. Data were analyzed by Chi-square and McNemar's tests. Results: Significant decreases were seen after treatment with metformin in extent of hair loss (P = 0.008, wrist circle (P = 0.011, weight (P = 0.047, diastolic BP (P = 0.023, and DHEA (P = 0.035. A significant decrease in TG was seen with pioglitazone treatment (P = 0.047. In both groups, significant decreases in acne, menstrual disturbance, FBS, and serum insulin were seen. Conclusion: There is a significant amelioration of endocrine and metabolic indices with pioglitazone in PCOS patients. Although we were not able to recommend one treatment regime over the other, pioglitazone offers a useful, alternate treatment in women with PCOS who are not able to tolerate metformin.

  16. Comparison clinical and metabolic effects of metformin and pioglitazone in polycystic ovary syndrome

    Science.gov (United States)

    Shahebrahimi, Karoon; Jalilian, Nasrin; Bazgir, Nasrin; Rezaei, Mansour

    2016-01-01

    Introduction: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. PCOS comprises a broad spectrum of anomalies, including hyperandrogenism, chronic anovulation, obesity, and infertility. Insulin resistance and its compensatory hyperinsulinemia play a key role in the pathogenicity of PCOS. This study compares the effects of 2 types of insulin sensitizer drugs, metformin and pioglitazone, on clinical, metabolic, and endocrine characteristics of women with PCOS. Methods: In this randomized clinical trial, 56 women with PCOS (ages 20–49 years) were treated orally with either metformin (500 mg 3 times daily) or pioglitazone (30 mg daily) for 3 months. Clinical (body weight, blood pressure [BP], and body mass index) and laboratory indices (fasting blood sugar [FBS], serum triglyceride [TG], cholesterol, low-density lipoprotein, high-density lipoprotein, insulin, testosterone, and dehydroepiandrosterone [DHEA]) were measured before and after therapy. Data were analyzed by Chi-square and McNemar's tests. Results: Significant decreases were seen after treatment with metformin in extent of hair loss (P = 0.008), wrist circle (P = 0.011), weight (P = 0.047), diastolic BP (P = 0.023), and DHEA (P = 0.035). A significant decrease in TG was seen with pioglitazone treatment (P = 0.047). In both groups, significant decreases in acne, menstrual disturbance, FBS, and serum insulin were seen. Conclusion: There is a significant amelioration of endocrine and metabolic indices with pioglitazone in PCOS patients. Although we were not able to recommend one treatment regime over the other, pioglitazone offers a useful, alternate treatment in women with PCOS who are not able to tolerate metformin. PMID:27867884

  17. Effect of pioglitazone on arterial baroreflex sensitivity and sympathetic nerve activity in patients with acute myocardial infarction and type 2 diabetes mellitus.

    Science.gov (United States)

    Yokoe, Hiroshi; Yuasa, Fumio; Yuyama, Reisuke; Murakawa, Kousuke; Miyasaka, Yoko; Yoshida, Susumu; Tsujimoto, Satoshi; Sugiura, Tetsuro; Iwasaka, Toshiji

    2012-06-01

    Pioglitazone has been shown to reduce the occurrence of fatal and nonfatal myocardial infarction (MI) in type 2 diabetes mellitus (DM). However, the mechanisms of such favorable effects remain speculative. The aim of this study was to investigate the effect of pioglitazone on arterial baroreflex sensitivity (BRS) and muscle sympathetic nerve activity (MSNA) in 30 DM patients with recent MI. Patients were randomly assigned to those taking pioglitazone (n = 15) and those not taking pioglitazone (n = 15) at 4 weeks after the onset of MI. BRS, MSNA, calculated homeostasis model assessment of insulin resistance index (HOMA-IR), and plasma adiponectin were measured at baseline and after 12 weeks. Pioglitazone increased plasma adiponectin (from 6.9 ± 3.3 μg/dL to 12.2 ± 7.1 μg/dL) and reduced HOMA-IR (from 4.0 ± 2.2 to 2.1 ± 0.9). In the pioglitazone group, MSNA decreased significantly (from 37 ± 7 bursts/min to 25 ± 8 bursts/min) and BRS increased significantly (from 6.7 ± 3.0 to 9.9 ± 3.2 ms/mm Hg) after 12 weeks. Furthermore, a significant relationship was found between the change in MSNA and HOMA-IR (r = 0.6, P = 0.042). Thus, pioglitazone decreased the sympathetic nerve traffic through the improvement of insulin resistance in DM patients with recent MI, which indicate that the sympathoinhibitory effects of pioglitazone may, at least in part, have contributed to the beneficial effects of pioglitazone.

  18. Enhancing pancreatic Beta-cell regeneration in vivo with pioglitazone and alogliptin.

    Directory of Open Access Journals (Sweden)

    Hao Yin

    Full Text Available AIMS/HYPOTHESIS: Pancreatic beta-cells retain limited ability to regenerate and proliferate after various physiologic triggers. Identifying therapies that are able to enhance beta-cell regeneration may therefore be useful for the treatment of both type 1 and type 2 diabetes. METHODS: In this study we investigated endogenous and transplanted beta-cell regeneration by serially quantifying changes in bioluminescence from beta-cells from transgenic mice expressing firefly luciferase under the control of the mouse insulin I promoter. We tested the ability of pioglitazone and alogliptin, two drugs developed for the treatment of type 2 diabetes, to enhance beta-cell regeneration, and also defined the effect of the immunosuppression with rapamycin and tacrolimus on transplanted islet beta mass. RESULTS: Pioglitazone is a stimulator of nuclear receptor peroxisome proliferator-activated receptor gamma while alogliptin is a selective dipeptidyl peptidase IV inhibitor. Pioglitazone alone, or in combination with alogliptin, enhanced endogenous beta-cell regeneration in streptozotocin-treated mice, while alogliptin alone had modest effects. In a model of syngeneic islet transplantation, immunosuppression with rapamycin and tacrolimus induced an early loss of beta-cell mass, while treatment with insulin implants to maintain normoglycemia and pioglitazone plus alogliptin was able to partially promote beta-cell mass recovery. CONCLUSIONS/INTERPRETATION: These data highlight the utility of bioluminescence for serially quantifying functional beta-cell mass in living mice. They also demonstrate the ability of pioglitazone, used either alone or in combination with alogliptin, to enhance regeneration of endogenous islet beta-cells as well as transplanted islets into recipients treated with rapamycin and tacrolimus.

  19. PPAR-γ agonist pioglitazone affects rat gouty arthritis by regulating cytokines.

    Science.gov (United States)

    Wang, R-C; Jiang, D-M

    2014-08-28

    The objective was to study peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone regulation effect and its mechanism of expression of cytokines on acute gouty arthritis synovial in rats. Rats with unilateral ankle were injected with artificial monosodium urate (MSU) crystals to make the acute gouty arthritis model. Taking the synovium 48 h after the injection of MSU and using RT-PCR, we assessed the effect of pioglitazone (20 mg·kg(-1)·day(-1), oral administration) on synovial expression, by detecting tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interferon-γ (IFN-γ). The pioglitazone treatment group showed synovial expression of TNF-α, and IFN-γ was significantly lower than in the control group; the inhibition rates were 78.5 and 60.4%. The IL-1 expression difference was not statistically significant between the two groups. Pioglitazone has anti-inflammatory effects on acute gouty arthritis by inhibiting the expression of TNF-α and IFN-γ.

  20. Efficacy and safety of colesevelam in combination with pioglitazone in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Rosenstock, J; Truitt, K E; Baz-Hecht, M; Ford, D M; Tao, B; Chou, H S

    2014-12-01

    Colesevelam improves glycemic control in patients with type 2 diabetes when added to existing metformin-, sulfonylurea-, or insulin-based regimens. We evaluated colesevelam's effects in subjects on stable pioglitazone-based therapy. This 24-week multicenter, double-blind, randomized, placebo-controlled study enrolled adults with type 2 diabetes who had suboptimal glycemic control [HbA1c ≥ 58 mmol/mol (7.5%) and ≤ 80 mmol/mol (9.5%)] on pioglitazone (30 or 45 mg) with or without 1-2 other oral antidiabetes medications. Subjects were randomized to colesevelam 3.8 g/day (n = 280) or placebo (n = 282) added to existing pioglitazone-based therapy. Primary efficacy variable was mean change in HbA1c from baseline to Week 24. Secondary variables included safety and tolerability, fasting plasma glucose changes, glycemic responses, and lipid profile. Tertiary variables included lipid particle profile changes by nuclear magnetic resonance. Colesevelam decreased HbA1c [least-squares mean treatment difference, - 3.5 mmol/mol (- 0.32%); p diabetes inadequately controlled with pioglitazone-based therapy, add-on colesevelam therapy improved glycemic control and lipid parameters and was well tolerated. ClinicalTrials.gov identifier: NCT00789750.

  1. Pioglitazone-induced Pulmonary Injury in a Very Elderly Patient.

    Science.gov (United States)

    Katayama, Kohta; Kumagai, Ryo; Isono, Momoko; Fujihara, Kazuya; Yagyu, Hiroaki; Ohara, Gen; Kagohashi, Katsunori; Satoh, Hiroaki

    2016-01-01

    An 85-year-old woman with diabetes mellitus was admitted to our hospital due to progressive dyspnea. Two months previously, pioglitazone had been newly prescribed for diabetes management. Bilateral ground-glass opacities and progressive respiratory deterioration suggested respiratory failure due to a drug-induced lung injury. With discontinuation of pioglitazone and the administration of a corticosteroid, an improvement in her respiratory condition was achieved, although sequelae remained in some areas of the lungs. Results of drug-induced lymphocyte stimulation tests were positive for pioglitazone. Resumption of other drugs did not reinduce the lung injury. Therefore, a diagnosis of pioglitazone-induced lung injury was made. Although pioglitazone-induced lung injury is very rare, clinicians should keep it in mind when pioglitazone is used.

  2. Evaluation of exposure to pioglitazone and risk of prostate cancer: a nested case–control study

    Science.gov (United States)

    Boxall, Naomi; Bennett, Dimitri; Hunger, Matthias; Dolin, Paul; Thompson, Paula L

    2016-01-01

    Objectives Investigate potential association between pioglitazone exposure and risk of prostate cancer. Research design and methods Nested, matched case–control study. UK primary care data (Clinical Practice Research Datalink (CPRD) GOLD) linked to inpatient (Hospital Episode Statistics (HES)) and cancer registry (National Cancer Information Network (NCIN)) data. English men aged ≥40 years diagnosed with type 2 diabetes mellitus, January 1, 2001 to January 5, 2015. Cases, with prostate cancer diagnosis, matched with up to 4 controls by age, cohort entry date and region. ORs for association of exposure to pioglitazone to incident prostate cancer, adjusted for potential confounders. Results From a cohort of 47 772 men with 243 923 person-years follow-up, 756 definite cases of prostate cancer were identified. Incidence was 309.9/100 000 person-years (95% CI 288.6 to 332.8). Pioglitazone use was not associated with prostate cancer risk; adjusted OR 0.759, 95% CI 0.502 to 1.148. Analyses showed no difference when possible cases, prostate cancer in CPRD GOLD only, included (adjusted OR 0.726, 95% CI 0.510 to 1.034). No association when adjusted for channeling bias (OR 0.778, 95% CI 0.511 to 1.184) or limited to an index date prior to July 1, 2011 (adjusted OR 0.508, 95% CI 0.294 to 0.879), despite prostate-specific antigen screening occurring more frequently among cases than controls (81.6% of 756 definite cases cf. 24.2% of 2942 controls (ppioglitazone use, increasing pioglitazone dose or increasing time since initiation. Conclusions In this real-world, nested matched case–control study, exposure to pioglitazone was not associated with increased risk of prostate cancer. PMID:28074141

  3. Effect of pioglitazone on muscle sympathetic nerve activity in type 2 diabetes mellitus with α-glucosidase inhibitor.

    Science.gov (United States)

    Kobayashi, Daisuke; Takamura, Masayuki; Murai, Hisayoshi; Usui, Soichiro; Ikeda, Tatsunori; Inomata, Jun-ichiro; Takashima, Shin-ichiro; Kato, Takeshi; Furusho, Hiroshi; Takeshita, Yumie; Ota, Tsuguhito; Takamura, Toshinari; Kaneko, Shuichi

    2010-12-08

    Activation of the sympathetic nervous system is augmented in patients with type 2 diabetes mellitus (DM). Pioglitazone, an anti-diabetic drug, improves insulin resistance, but its influence on sympathetic nerve activity is not clear. To identify the relationship between insulin resistance and sympathetic activity, we examined muscle sympathetic nerve activity (MSNA) in controlled type 2 DM patients with alpha-glucosidase inhibitor (GI). We measured MSNA and calculated homeostasis model assessment of insulin resistance index (HOMA-IR) in twelve DM patients treated with alpha-GI and thirteen age-matched healthy subjects. In DM patients with alpha-GI, all parameters were reexamined after three months of treatment with pioglitazone. MSNA and HOMA-IR were significantly greater in DM patients with alpha-GI compared to healthy subjects. Hemoglobin A1c did not differ in DM patients before and after pioglitazone. However, pioglitazone significantly decreased MSNA in DM patients compared with alpha-GI (21.7±5.2 vs. 32.0±6.8 burst/min, ppioglitazone was similar to that in healthy subjects. HOMA-IR significantly decreased after pioglitazone, and a significant relationship was found between the absolute change in MSNA and HOMA-IR (r=0.65, ppioglitazone provides an additional effect on inhibition of sympathetic nerve activity.

  4. Pioglitazone attenuates cardiac fibrosis and hypertrophy in a rat model of diabetic nephropathy.

    Science.gov (United States)

    Elrashidy, Rania A; Asker, Mervat E; Mohamed, Hoda E

    2012-09-01

    Pioglitazone has been demonstrated to have beneficial effects on cardiovascular outcomes. However, little is known about its effect on cardiac remodeling associated with diabetic nephropathy. Therefore, this study was designed to study the effects of pioglitazone on cardiac fibrosis and hypertrophy in a rat model of diabetic nephropathy. For this purpose, male Wistar albino rats were randomly assigned into 4 groups (n = 10 per group): normal (N) group, diabetic (D) group, diabetic nephropathic (DN) group received an equal amount of vehicle (0.5% carboxy methyl cellulose), and diabetic nephropathic group treated by oral administration of pioglitazone (10 mg/kg per d) for 4 weeks. Diabetic nephropathy was induced by subtotal nephrectomy plus streptozotocin (STZ) injection. The results revealed that DN rats showed excessive deposition of collagen fibers in their cardiac tissue, along with a marked myocyte hypertrophy. This was associated with a dramatic upregulation of cardiac transforming growth factor-β1 (TGF-β1) gene. Furthermore, the gene expression of matrix metalloproteinase 2 (MMP-2) decreased, while the gene expression of tissue inhibitor of metalloproteinase 2 (TIMP-2) increased in the hearts of DN rats. In addition, enhanced lipid peroxidation and myocardial injury, evidenced by a significant increase in their serum creatine kinase-MB level were observed in DN rats. All these abnormalities were ameliorated by pioglitazone administration. Our findings suggest that upregulation of cardiac TGF-β1 gene along with the imbalance between MMP-2 and TIMP-2 expressions is critically involved in cardiac fibrosis associated with diabetic nephropathy. Pioglitazone can ameliorate cardiac remodeling by suppressing the gene expression of TGF-β1 and regulating the MMP-2/TIMP-2 system.

  5. Replicate study design in bioequivalency assessment, pros and cons: bioavailabilities of the antidiabetic drugs pioglitazone and glimepiride present in a fixed-dose combination formulation.

    Science.gov (United States)

    Karim, Aziz; Zhao, Zhen; Slater, Margaret; Bradford, Dawn; Schuster, Jennifer; Laurent, Aziz

    2007-07-01

    An open-label, randomized, 2-sequence, 4-period crossover (7-day washout period between treatment), replicate design study was conducted in 37 healthy subjects to assess intersubject and intrasubject variabilities in the peak (Cmax) and total (AUC) exposures to 2 oral antidiabetic drugs, pioglitazone and glimepiride, after single doses of 30 mg pioglitazone and 4 mg glimepiride, given under fasted state, as commercial tablets coadministered or as a single fixed-dose combination tablet. Variabilities for AUC(infinity) for coadministered and fixed-dose combination treatments were similar: 16% to 19% (intra) and 23% to 25% (inter) for pioglitazone and 18% to 19% (intra) and 29% to 30% for glimepiride (inter, excluding 1 poor metabolizer). Fixed-dose combination/coadministered least squares mean ratios of >or=0.86 and the 90% confidence intervals of these ratios for pioglitazone and glimepiride of between 0.80 and 1.25 for Cmax, AUC(lqc), and AUC(infinity) met the bioequivalency standards. Gender analysis showed that women showed mean of 16% and 30% higher exposure than men for glimepiride (excluding 1 poor metabolizer) and pioglitazone, respectively. There was considerable overlapping in the AUC(infinity) values, making gender-dependent dosing unnecessary. Patients taking pioglitazone and glimepiride as cotherapy may replace their medication with a single fixed-dose combination tablet containing these 2 oral antidiabetic drugs.

  6. Pioglitazone suppresses advanced glycation end product-induced expression of plasminogen activator inhibitor-1 in vascular smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    Xiaochen Yuan; Naifeng Liu

    2011-01-01

    Advanced glycation end products (AGEs) play an important role in vascular complications of diabetes, including fibrinolytic abnormalities.Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARΥ) agonist, has recently been shown to reduce circulating plasminogen activator inhibitor-1 (PAI-1) levels in diabetes mellitus. In the present study, we investigated the effects of pioglitazone on the expression of local PAI-1 in rat vascular smooth muscle cells (VSMCs) induced by AGEs and the underlying mechanism. The result showed that AGEs could enhance the PAI-1 expression by 5.1-fold in mRNA and 2.7-fold in protein level, as evaluated by real-time RT-PCR and Western blotting,respectively. Pioglitazone was found to down-regulate the AGE-stimulated PAI-1 expression in VSMCs. However, these inhibitory effects were partially attenuated by the PPARΥ antagonist, GW9662. Furthermore, we found that AGEs induced a rapid increase in phosphorylation and activation of extracellular signal-regulated protein kinase 1/2 (ERK 1/2). The ERK kinase inhibitor, UO126, partially prevented the induction of PAI-1 by AGEs. Moreover, pioglitazone was also found to inhibit the phosphorylation of ERKi/2. Taken together, it was concluded that pioglitazone could inhibit AGE-induced PAI-1 expression, which was mediated by the ERK1/2 and PPARΥ pathways. Our findings suggestedpioglitazone had a therapeutic potential in improving fibrinolytic activity, and consequently preventing thromboembolic complications of diabetes and cardiovascular disease.

  7. Do thiazolidinediones still have a role in treatment of type 2 diabetes mellitus?

    Science.gov (United States)

    Consoli, A; Formoso, G

    2013-11-01

    Thiazolidinediones have been introduced in the treatment of type 2 diabetes mellitus (T2DM) since the late 1990s. Although troglitazone was withdrawn from the market a few years later due to liver toxicity, both rosiglitazone and pioglitazone gained widespread use for T2DM treatment. In 2010, however, due to increased risk of cardiovascular events associated with its use, the European Medicines Agency recommended suspension of rosiglitazone use and the Food and Drug Administration severely restricted its use. Thus pioglitazone is the only thiazolidinedione still significantly employed for treating T2DM and it is the only molecule of this class still listed in the American Diabetes Association-European Association for the Study of Diabetes 2012 Position Statement. However, as for the other thiazolidinediones, use of pioglitazone is itself limited by several side effects, some of them potentially dangerous. This, together with the development of novel therapeutic strategies approved in the last couple of years, has made it questionable whether or not thiazolidinediones (namely pioglitazone) should still be used in the treatment of T2DM. This article will attempt to formulate an answer to this question by critically reviewing the available data on the numerous advantages and the potentially worrying shortcomings of pioglitazone treatment in T2DM.

  8. Effects of pioglitazone on cognition function and expression of TNF-α and Aβ in hippocampal tissues of diabetic rats%吡格列酮对糖尿病大鼠认知功能及海马组织TNF-α、Aβ的影响

    Institute of Scientific and Technical Information of China (English)

    向慧; 徐寒松; 赵胜

    2011-01-01

    OBJECTIVE To observe the effects of pioglitazone on cognition function and expression of tumor necrosis factorα(TNF-α) and β-amyloid peptide (Aβ) in hippocampal tissues of diabetic rats. METHODS Forty-five Wistar rats were randomly divided into normal control group, diabetic model group, and pioglitazone treatment group. Streptozotocin-induced diabetic rat model was established. In the pioglitazone treatment group, the rats were treated with pioglitazone for 12 weeks. The cognition ability of rats was assayed with the Morris water maze test. The expression of TNF-α and Aβ was detected by ELISA. RFSULTS The Morris water maze test showed that escape latency was longer in the pioglitazone treatment group and the diabetic model group than that in the normal control group (P<0. 05), Compared with the diabetic model group, the pioglitazone treatment group showed a significant decrease in the mean time of escape latencies (P<0. 05), and an increased percentage of time spent in the central area and the more times navigating the original platform position(P<0. 05). The expression of TNF-α and Aβ in the pioglitazone treatment and the diabetic model groups was significantly higher than that in normal group (P<0. 01 ). Compared with diabetic model group, the expression of TNF-α and Aβ in pioglitazone treatment group was decreased(P<0. 05). CONCLUSION There exists impairment of cognitive function in diabetic rats, pioglitazone therapy can improve cognition function in diabetic rat. This may be related to it s effect of decreasing the expression of TNF-α and Aβ.%目的:观察吡格列酮对糖尿病大鼠认知功能及海马组织TNF-α、β-淀粉样蛋白(Aβ)的影响.方法:随机将45只Wistar大鼠分为正常对照组、糖尿病组、吡格列酮组,STZ25mg·kg-1腹腔注射建立糖尿病大鼠模型,给予吡格列酮10mg·kg-1·d-1灌胃干预12周后,采用Morris水迷宫试验测试其认知能力,ELISA法检测各组大鼠海马组织TNF-α

  9. Modulating effects of omega-3 fatty acids and pioglitazone combination on insulin resistance through toll-like receptor 4 in type 2 diabetes mellitus.

    Science.gov (United States)

    Eraky, Salma M; Abdel-Rahman, Noha; Eissa, Laila A

    2017-06-17

    Toll-like receptor 4 (TLR-4) plays important roles in innate immunity. Changes in the reduction-oxidation balance of tissues can lead to a pro-inflammatory state and insulin resistance. An action thought to be mediated by TLRs. Omega-3 fatty acids and Peroxisome Proliferator Activated Receptor gamma (PPAR-γ) agonists as pioglitazone are used for decreasing inflammation. The aim of this study is to investigate the anti-diabetic effects of combining omega -3 fatty acid with pioglitazone on type 2 diabetes, and the modifying effects on TLR-4. Type 2 diabetes was induced in male Sprague-Dawley rats by combination of high fat diet and low dose streptozotocin (35mg/kg). Diabetic rats were treated with omega-3 fatty acids (10% W/W diet), pioglitazone (20mg/kg), and their combination for 4 weeks. Omega-3 fatty acids and the combination treatment significantly decreased TLR-4 activation. Omega-3 fatty acids, pioglitazone, and their combination significantly decreased TLR-4 mRNA expression, hepatic malondialdehyde, total cholesterol and triglycerides levels, compared to diabetic group. Pioglitazone and the combination significantly decreased blood glucose levels and improved insulin resistance. In conclusion, combining omega-3 fatty acids with pioglitazone showed potential effects in lowering blood glucose levels and improving lipid profile and insulin resistance. Such effects are mediated through modulation of TLR-4. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Pioglitazone could induce remission in major depression: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Colle R

    2016-12-01

    Full Text Available Romain Colle,1,* Delphine de Larminat,1,* Samuel Rotenberg,1 Franz Hozer,1 Patrick Hardy,1 Céline Verstuyft,2 Bruno Fève,3,* Emmanuelle Corruble1,* 1Psychiatry Department, Hôpital Bicêtre, INSERM, UMR S1178, University Paris-Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France; 2Molecular Genetic, Pharmacogenetics and Hormonology Department, Hôpital Bicêtre, INSERM UMR_S1184, Centre IMVA, University Paris-Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France; 3Endocrinology Department, INSERM UMR_S938, Hôpital Saint-Antoine, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire ICAN, Sorbonne Universités, Université Pierre et Marie Curie, Assistance Publique des Hôpitaux de Paris, Paris, France *These authors contributed equally to this work Background: Pioglitazone, a selective agonist of the nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-γ, prescribed for the treatment of type 2 diabetes, could have antidepressant properties. However, its potential to induce remission of major depressive episodes, the optimal clinical target for an antidepressant drug, is a matter of concern. Indeed, only one out of four double-blind randomized controlled trials show higher remission rates with pioglitazone than with control treatments. Hence, the main aim of this study was to perform a meta-analysis of the efficacy of pioglitazone for the treatment of MDE, focusing on remission rates.Methods: Four double-blind randomized controlled trials, comprising 161 patients with an MDE, were included in this meta-analysis. Pioglitazone was studied either alone (one study or as add-on therapy to conventional treatments (antidepressant drugs or lithium salts. It was compared either to placebo (three studies or to metformin (one study. Remission was defined by a Hamilton Depression Rating Scale score <8 after treatment.Results: Pioglitazone could induce higher remission

  11. Pioglitazone enhances mitochondrial biogenesis and ribosomal protein biosynthesis in skeletal muscle in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Skov, Vibe; Glintborg, Dorte; Knudsen, Steen

    2008-01-01

    Insulin resistance is a common metabolic abnormality in women with PCOS and leads to an elevated risk of type 2 diabetes. Studies have shown that thiazolidinediones (TZDs) improve metabolic disturbances in PCOS patients. We hypothesized that the effect of TZDs in PCOS is, in part, mediated...... by changes in the transcriptional profile of muscle favoring insulin sensitivity. Using Affymetrix microarrays, we examined the effect of pioglitazone (30 mg/day for 16 weeks) on gene expression in skeletal muscle of 10 obese women with PCOS metabolically characterized by a euglycemic-hyperinsulinemic clamp....... Moreover, we explored gene expression changes between these PCOS patients before treatment and 13 healthy women. Treatment with pioglitazone improved insulin-stimulated glucose metabolism and plasma adiponectin, and reduced fasting serum insulin (all P

  12. Risk of cardiovascular events with rosiglitazone and pioglitazone treatment in over 65-year-old patients with type 2 diabetes mellitus: a meta-analysis%罗格列酮和吡格列酮对65岁以上糖尿病患者心血管事件风险的meta分析

    Institute of Scientific and Technical Information of China (English)

    陈忻; 杨丽; 翟所迪

    2011-01-01

    Objective : To systematically evaluate the risk of cardiovascular events with rosiglitazone and pioglitazone treatment in over 65-year-old patients with type 2 diabetes mellitus. Methods: A search of Cochrane Library ( 1996 to 2010) , PubMed (1966 to 2010) , Embase (1966 to 2010), CIFD (1979 to 2010), CBM (1978 to 2010) and VIP (1989 to 2010) were conducted using keywords " rosiglitazone" , " pioglitazone" , " cardiovascular events " , " cardiovascular risk " , " elderly population" , " 65 years old" , and "cohort study " . Retrospective cohort studies in comparison of cardiovascular events between rosiglitazone and pioglitazone in over 65-year-old patients with type 2 diabetes mellitus were collected. According to the inclusion criteria, the literature was selected and assessed. The meta-analysis of data was conducted using RevMan 5.0 software. The relative risk ratio (RR) and 95% confidence interval ( CI) of myocardial infarction, heart failure, and all-cause mortality due to rosiglitazone or pioglitazone treatment in over 65-year-old patients with type 2 diabetes mellitus were calculated. Results : Seventy-four related articles were obtained and, after detailed screening, three retrospective cohort studies from 2008 to 2010 were located, with a total of 295 668 patients (including 104 479 receiving rosiglitazone and 191 189 receiving pioglitazone) . The meta-analysis revealed the following results : the incidence rates of myocardial infarction, heart failure and total mortality in the patients receiving rosiglitazone were higher than those in the patients receiving pioglitazone , their RR ( 95% CI) were 1. 05 ( 0. 98-1. 13, P = 0. 17) ,1. 22 ( 1. 05-1, 40 ,P = 0. 007) and 1. 14 ( 1. 08-1. 21 ,P <0. 000 01) ,respectively. Conclusion: The risk of heart failure and all-cause mortality is higher in rosiglitazone treatment than in pioglitazone treatment in over 65-year-old patients with type 2 diabetes mellitus.%目的:系统评价

  13. Pioglitazone is equally effective for diabetes prevention in older versus younger adults with impaired glucose tolerance.

    Science.gov (United States)

    Espinoza, Sara E; Wang, Chen-Pin; Tripathy, Devjit; Clement, Stephen C; Schwenke, Dawn C; Banerji, Mary Ann; Bray, George A; Buchanan, Thomas A; Henry, Robert R; Kitabchi, Abbas E; Mudaliar, Sunder; Stentz, Frankie B; Reaven, Peter D; DeFronzo, Ralph A; Musi, Nicolas

    2016-12-01

    To determine the efficacy of pioglitazone to prevent type 2 diabetes in older compared to younger adults with pre-diabetes. Six hundred two participants with impaired glucose tolerance (IGT) were randomized in double blind fashion to placebo or pioglitazone for diabetes prevention in the ACT NOW study (NEJM 364:1104-1115, 2011). Cox proportional hazard regression was used to compare time to development of diabetes over a mean of 2 years between older (≥61 years) and younger participants. We compared effects of pioglitazone versus placebo on metabolic profiles, inflammatory markers, adipokines, β cell function (disposition index), insulin sensitivity (Matsuda index), and body composition by ANOVA. Diabetes incidence was reduced by 85 % in older and 69 % in younger subjects (p = 0.41). β cell function (disposition index) increased by 35.0 % in the older and 26.7 % in younger subjects (p = 0.83). Insulin sensitivity (Matsuda index) increased by 3.07 (5.2-fold) in older and by 2.54 (3.8-fold) in younger participants (p = 0.58). Pioglitazone more effectively increased adiponectin in older versus younger subjects (22.9 ± 3.2 μg/mL [2.7-fold] vs. 12.7 ± 1.4 μg/mL [2.2-fold], respectively; p = 0.04). Younger subjects tended to have a greater increase in whole body fat mass compared to older subjects (3.6 vs. 3.1 kg; p = 0.061). Younger and older subjects had similar decreases in bone mineral density (0.018 ± 0.0071 vs. 0.0138 ± 0.021 g/cm(2)). Younger and older pre-diabetic adults taking pioglitazone had similar reductions in conversion to diabetes and older adults had similar or greater improvements in metabolic risk factors, demonstrating that pioglitazone is useful in preventing diabetes in older adults.

  14. Cardiovascular safety of rosiglitazone and pioglitazone%罗格列酮和吡格列酮的心血管安全性

    Institute of Scientific and Technical Information of China (English)

    卢宇; 马德琳; 余学锋

    2015-01-01

    Rosiglitazone and pioglitazone belong to thiazolidinediones( TZD)insulin sensitizers, mainly used for the treatment of type 2 diabetes. Rosiglitazone was restricted to use or withdrawn from the market due to possibly increased cardiovascular events in 2010,and then was released for insufficient evidence in 2013. The large prospective clinical trial and Meta-analysis indicated that pioglitazone has cardiovascular protective effect,since the drug reduced risk of myocardial infarction/stroke/death of patients with type 2 diabetes. The different cardiovascular risk of rosiglitazone and pioglitazone maybe related to the differences in effect on lipid metabolism or in gene regulation.%罗格列酮和吡格列酮同属为噻唑烷二酮类胰岛素增敏剂,主要用于2型糖尿病的治疗。罗格列酮因可能增加心血管事件风险于2010年被限用(美国)或禁用(欧洲),2013年又因增加心血管事件风险证据不足被解禁。吡格列酮上市后的大型前瞻性临床研究和Meta分析结果显示,该药可以使2型糖尿病患者心肌梗死/中风/死亡的风险降低,从而被认为有心血管保护作用。罗格列酮和吡格列酮心血管风险的差异,可能与它们对2型糖尿病患者脂代谢影响的不同有关,也可能与其基因调控的不同有关。

  15. Taurine and pioglitazone attenuate diabetes-induced testicular damage by abrogation of oxidative stress and up-regulation of the pituitary-gonadal axis.

    Science.gov (United States)

    Abd El-Twab, Sanaa M; Mohamed, Hanaa M; Mahmoud, Ayman M

    2016-06-01

    Chronic hyperglycemia is associated with impairment of testicular function. The current study aimed to investigate the protective effects and the possible mechanisms of taurine and pioglitazone against diabetes-induced testicular dysfunction in rats. Diabetes was induced by streptozotocin injection. Both normal and diabetic rats received taurine (100 mg/kg) or pioglitazone (10 mg/kg) orally and daily for 6 weeks. Diabetic rats showed a significant (P Taurine and pioglitazone alleviated hyperglycemia, decreased pro-inflammatory cytokines, and increased circulating levels of insulin, testosterone, LH, and FSH. Gene and protein expression of LH and FSH receptors and cytochrome P450 17α-hydroxylase (CYP17) was significantly (P taurine and pioglitazone. In addition, taurine and pioglitazone significantly decreased lipid peroxidation and DNA damage, and enhanced activity of the antioxidant enzymes in testes of diabetic rats. In conclusion, taurine and pioglitazone exerted protective effects against diabetes-induced testicular damage through attenuation of hyperglycemia, inflammation, oxidative stress and DNA damage, and up-regulation of the pituitary/gonadal axis.

  16. Pioglitazone improves reversal learning and exerts mixed cerebrovascular effects in a mouse model of Alzheimer's disease with combined amyloid-β and cerebrovascular pathology.

    Directory of Open Access Journals (Sweden)

    Panayiota Papadopoulos

    Full Text Available Animal models of Alzheimer's disease (AD are invaluable in dissecting the pathogenic mechanisms and assessing the efficacy of potential new therapies. Here, we used the peroxisome proliferator-activated receptor gamma agonist pioglitazone in an attempt to rescue the pathogenic phenotype in adult (12 months and aged (>18 months bitransgenic A/T mice that overexpress a mutated human amyloid precursor protein (APPSwe,Ind and a constitutively active form of transforming growth factor-β1 (TGF-β1. A/T mice recapitulate the AD-related cognitive deficits, amyloid beta (Aβ and cerebrovascular pathologies, as well as the altered metabolic and vascular coupling responses to increased neuronal activity. Pioglitazone normalized neurometabolic and neurovascular coupling responses to sensory stimulation, and reduced cortical astroglial and hippocampal microglial activation in both age groups. Spatial learning and memory deficits in the Morris water maze were not rescued by pioglitazone, but reversal learning was improved in the adult cohort notwithstanding a progressing Aβ pathology. While pioglitazone preserved the constitutive nitric oxide synthesis in the vessel wall, it unexpectedly failed to restore cerebrovascular reactivity in A/T mice and even exacerbated the dilatory deficits. These data demonstrate pioglitazone's efficacy on selective AD hallmarks in a complex AD mouse model of comorbid amyloidosis and cerebrovascular pathology. They further suggest a potential benefit of pioglitazone in managing neuroinflammation, cerebral perfusion and glucose metabolism in AD patients devoid of cerebrovascular pathology.

  17. 二甲双胍配伍吡格列酮治疗2型糖尿病临床效果及安全性分析%Metformin Combined with Pioglitazone Treatment in Type 2 Diabetes Mellitus Clinical Efficacy and Safety Analysis

    Institute of Scientific and Technical Information of China (English)

    梁文杰

    2013-01-01

    Objective:To explore the combination of metformin pioglitazone treatment in type 2 diabetes:clinical efficacy and safety. Methods:100 cases of patients with type 2 diabetes were randomly divided into the observation group and the control group with 50 cases in each group, the observation group was treated with pioglitazone metformin treatment regimens, controls individually using metformin treatment, a total of16 weeks treatment. Treatment in the two groups were observed before and after fasting, postprandial glucose and insulin sensitivity in2h, adverse reactions and other indexes, comparing the two groups of clinical curative effect analysis of metformin, pioglitazone treatment in type 2diabetes mellitus with safety. Results: The observation group efficiency is 96%, the effective rate of control group was76%, between the two groups, the observation group was better than the control group, the difference was significant ( P0.05). Conclusion:Combined pioglitazone and metformin in treating type 2 diabetes mellitus, can effectively control FPG,2h postprandial plasma glucose, enhanced insulin sensitivity, improve insulin resistance, the effect is better than the single use of metformin, and the security is good.%  目的:探讨二甲双胍配伍吡格列酮治疗2型糖尿病临床效果及其安全性。方法:将我院100例2型糖尿病患者随机分为观察组和对照组各50例,观察组采用二甲双胍配伍吡格列酮治疗方案,对照组单独使用二甲双胍治疗,共治疗16周。观察两组治疗前后空腹、餐后2h血糖及胰岛素敏感性、不良反应等指标,对比两组临床疗效,分析二甲双胍配伍吡格列酮治疗2型糖尿病的安全性。结果:观察组有效率为96.0%,对照组有效率为76.0%,两组疗效对比,观察组明显优于对照组,差异具有显著性(P0.05)。结论:吡格列酮联合二甲双胍治疗2型糖尿病,能有效地控制FPG、餐后2h血糖水平,增强胰

  18. Formulation and Evaluation of Multilayered Tablets of Pioglitazone Hydrochloride and Metformin Hydrochloride

    Directory of Open Access Journals (Sweden)

    Y. Ankamma Chowdary

    2014-01-01

    Full Text Available In the treatment of type 2 diabetes mellitus a continuous therapy is required which is a more complex one. As in these patients there may be a defect in both insulin secretion and insulin action exists. Hence, the treatment depends on the pathophysiology and the disease state. In the present study, multilayered tablets of pioglitazone hydrochloride 15 mg and metformin hydrochloride 500 mg were prepared in an attempt for combination therapy for the treatment of type 2 diabetes mellitus. Pioglitazone HCl was formulated as immediate release layer to show immediate action by direct compression method using combination of superdisintegrants, namely, crospovidone and avicel PH 102. Crospovidone at 20% concentration showed good drug release profile at 2 hrs. Metformin HCl was formulated as controlled release layer to prolong the drug action by incorporating hydrophilic polymers such as HPMC K4M by direct compression method and guar gum by wet granulation method in order to sustain the drug release from the tablets and maintain its integrity so as to provide a suitable formulation. The multilayered tablets were prepared after carrying out the optimization of immediate release layer and were evaluated for various precompression and postcompression parameters. Formulation F13 showed 99.97% of pioglitazone release at 2 hrs in 0.1 N HCl and metformin showed 98.81% drug release at 10 hrs of dissolution in 6.8 pH phosphate buffer. The developed formulation is equivalent to innovator product in view of in vitro drug release profile. The results of all these evaluation tests are within the standards. The procedure followed for the formulation of these tablets was found to be reproducible and all the formulations were stable after accelerated stability studies. Hence, multilayered tablets of pioglitazone HCl and metformin HCl can be a better alternative way to conventional dosage forms.

  19. Pioglitazone administration alters ovarian gene expression in aging obese lethal yellow mice

    Directory of Open Access Journals (Sweden)

    Weber Mitch

    2008-03-01

    Full Text Available Abstract Background Women with polycystic ovary syndrome (PCOS are often treated with insulin-sensitizing agents, e.g. thiazolidinediones (TZD, which have been shown to reduce androgen levels and improved ovulatory function. Acting via peroxisome proliferator-activated receptor (PPAR gamma, TZD alter the expression of a large variety of genes. Lethal yellow (LY; C57BL/6J Ay/a mice, possessing a mutation (Ay in the agouti gene locus, exhibit progressive obesity, reproductive dysfunction, and altered metabolic regulation similar to women with PCOS. The current study was designed to test the hypothesis that prolonged treatment of aging LY mice with the TZD, pioglitazone, alters the ovarian expression of genes that may impact reproduction. Methods Female LY mice received daily oral doses of either 0.01 mg pioglitazone (n = 4 or an equal volume of vehicle (DMSO; n = 4 for 8 weeks. At the end of treatment, ovaries were removed and DNA microarrays were used to analyze differential gene expression. Results Twenty-seven genes showed at least a two-fold difference in ovarian expression with pioglitazone treatment. These included leptin, angiopoietin, angiopoietin-like 4, Foxa3, PGE1 receptor, resistin-like molecule-alpha (RELM, and actin-related protein 6 homolog (ARP6. For most altered genes, pioglitazone changed levels of expression to those seen in untreated C57BL/6J(a/a non-mutant lean mice. Conclusion TZD administration may influence ovarian function via numerous diverse mechanisms that may or may not be directly related to insulin/IGF signaling.

  20. Pioglitazone inhibits the expression of matrix metalloproteinase-9, a protein involved in diabetes-associated wound healing.

    Science.gov (United States)

    Zhang, Jun; Huang, Xiaoyuan; Wang, Lingfeng

    2014-08-01

    Matrix metalloproteinase-9 (MMP-9) is a protein involved in diabetes-associated wound healing. The present study aimed to determine whether pioglitazone, an agonist of peroxisome proliferator-activated receptor‑γ (PPAR-γ), inhibits the expression of MMP-9. HaCaT cells at a density of 6x105 cells/well were seeded into 6-well plates in medium and were cultured for 24 h. The cells were then treated with bovine serum albumin (BSA) only or advanced glycation end‑product (AGE)-BSA (50, 100, 200, 300 or 400 µg/ml), with or without pioglitazone (0.5 or 1 µM). The effects of AGE-BSA on cell viability were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The levels of MMP-9 secreted into the medium were detected by an enzyme-linked immunosorbent assay. The mRNA and protein levels were analyzed by quantitative polymerase chain reaction (qPCR) and western blot analysis, respectively. AGEs are able to increase the level of MMP-9 mRNA in HaCaT cells and the levels of MMP-9 protein secreted into the medium. Pioglitazone (0.5 or 1 µΜ) significantly inhibited the levels of MMP-9 in the treated HaCaT cells. Pioglitazone (0.5 or 1 µΜ) also suppressed the levels of MMP-9 in the cell culture medium. Pioglitazone at concentrations of 0.5 and 1 µΜ significantly suppressed the levels of MMP-9 mRNA to 20 or 8%, respectively. These results suggest that pioglitazone is able to effectively suppress the expression of MMP-9 via a transcriptional mechanism.

  1. Pioglitazone: a valuable component of combination therapy for type 2 diabetes mellitus.

    Science.gov (United States)

    Papanas, Nikolaos; Katsiki, Niki; Hatzitolios, Apostolos I; Maltezos, Efstratios

    2011-07-01

    Several classes of drugs have been developed to treat type 2 diabetes mellitus (T2DM). Pioglitazone is now the only thiazolidinedione approved for the treatment of T2DM and can be administered in combination with metformin, sulfonylureas, exenatide, dipeptidyl peptidase 4 (DPP-4) inhibitors or insulin. It improves glycemic control with an extremely low incidence of hypoglycemia. In addition to reducing insulin resistance, it may also improve pancreatic beta-cell secretory function. Moreover, it exhibits a variety of favorable pleiotropic effects. The latter include anti-inflammatory, antioxidant, vasoprotective, antihypertensive and hypolipidemic actions. Finally, this agent has been shown to improve experimental diabetic neuropathy and alleviate neuropathic pain, as well as decreasing urinary albumin excretion in patients with diabetes. Thus, pioglitazone emerges as a valuable hypoglycemic agent for combination therapy in T2DM. Importantly, however, patients should be appropriately selected, especially to avoid those with heart failure, in order to minimize adverse events attributable to water retention.

  2. 吡格列酮对db/db小鼠骨骼肌蛋白酪氨酸磷酸酶1B表达的影响%The Effects of Pioglitazone on Expression of Protein Tyrosine Phosphatase 1 B in Muscle of db/db Mice

    Institute of Scientific and Technical Information of China (English)

    卢斌; 顾萍; 邵加庆; 杜宏; 王坚

    2012-01-01

    目的 探讨吡格列酮对db/db小鼠骨骼肌蛋白酪氨酸磷酸酶1B( protein tyrosine phosphatase 1B,PTP1B)表达水平的影响.方法 将20只4周龄db/db小鼠随机分为两组(吡格列酮组和db/db对照组),每组10只,分别给予吡格列酮10mg/kg.d和安慰剂灌胃.另设10只同周龄db/m小鼠,给予安慰剂灌胃作为非糖尿病对照(db/m对照组).每周监测体重、血糖,4周后用蛋白印迹法检测各组小鼠骨骼肌组织中PTP1 B蛋白含量.结果 db/db组小鼠骨骼肌PTP1B表达显著高于db/m组,给予吡格列酮干预,血糖、胰岛素抵抗指数显著低于db/db组(P<0.05),骨骼肌PTP1B表达水平亦显著降低(P<0.05).结论吡格列酮改善胰岛素抵抗,可能与降低骨骼肌PTP1B蛋白表达有关.%Objective To explore the effects of pioglitazone on expression of protein tyrosine phosphatase 1B in muscle of db/db mice. Methods Twenty db/db mice aged 4 weeks were randomized to pioglitazone group ( PIO group) and db/db group, fed with 10mg/kg·d pioglitazone and placebo respectively. Ten age-matched db/misty mice were concurrently treated with placebo as non-diabetic control group (db/m group). Body weight and blood glucose were measured every week. After 4 weeks'treatment, the expression of PTP1B in muscle of mice were determined with Western blotting. Results The expression of PTP1B in muscle of db/db mice significantly increased compared with db/m( P < 0. 05 ). Pioglitazone treatment significantly decreased fasting blood glucose and HOMA-IR. The expression of PTP1B in muscle of pioglitazone-treated mice obviously decreased compared with db/db group ( P < 0.05 ). Conclusion Pioglitazone treatment could improve insulin resistance possibly by reducing the expression level of PTP1B in the muscle.

  3. Cardiac Outcomes After Ischemic Stroke or Transient Ischemic Attack: Effects of Pioglitazone in Patients With Insulin Resistance Without Diabetes Mellitus.

    Science.gov (United States)

    Young, Lawrence H; Viscoli, Catherine M; Curtis, Jeptha P; Inzucchi, Silvio E; Schwartz, Gregory G; Lovejoy, Anne M; Furie, Karen L; Gorman, Mark J; Conwit, Robin; Abbott, J Dawn; Jacoby, Daniel L; Kolansky, Daniel M; Pfau, Steven E; Ling, Frederick S; Kernan, Walter N

    2017-05-16

    Insulin resistance is highly prevalent among patients with atherosclerosis and is associated with an increased risk for myocardial infarction (MI) and stroke. The IRIS trial (Insulin Resistance Intervention after Stroke) demonstrated that pioglitazone decreased the composite risk for fatal or nonfatal stroke and MI in patients with insulin resistance without diabetes mellitus, after a recent ischemic stroke or transient ischemic attack. The type and severity of cardiac events in this population and the impact of pioglitazone on these events have not been described. We performed a secondary analysis of the effects of pioglitazone, in comparison with placebo, on acute coronary syndromes (MI and unstable angina) among IRIS participants. All potential acute coronary syndrome episodes were adjudicated in a blinded fashion by an independent clinical events committee. The study cohort was composed of 3876 IRIS participants, mean age 63 years, 65% male, 89% white race, and 12% with a history of coronary artery disease. Over a median follow-up of 4.8 years, there were 225 acute coronary syndrome events, including 141 MIs and 84 episodes of unstable angina. The MIs included 28 (19%) with ST-segment elevation. The majority of MIs were type 1 (94, 65%), followed by type 2 (45, 32%). Serum troponin was 10× to 100× upper limit of normal in 49 (35%) and >100× upper limit of normal in 39 (28%). Pioglitazone reduced the risk of acute coronary syndrome (hazard ratio, 0.71; 95% confidence interval, 0.54-0.94; P=0.02). Pioglitazone also reduced the risk of type 1 MI (hazard ratio, 0.62; 95% confidence interval, 0.40-0.96; log-rank P=0.03), but not type 2 MI (hazard ratio, 1.05; 95% confidence interval, 0.58-1.91; P=0.87). Similarly, pioglitazone reduced the risk of large MIs with serum troponin >100× upper limit of normal (hazard ratio, 0.44; 95% confidence interval, 0.22-0.87; P=0.02), but not smaller MIs. Among patients with insulin resistance without diabetes mellitus

  4. DEVELOPMENT AND EVALUATION OF MICROBALLOONS OF PIOGLITAZONE HYDROCHLORIDE USING EUDRAGIT S-100

    OpenAIRE

    Nishant S. Gandhi et al.

    2012-01-01

    ABSTRACTKeywords:Pioglitazone hydrochloride,Eudragit S-100,Solvent diffusion evaporation,Floating microspheres,Polymer: Drug ratioCorrespondence to Author:Nishant GandhiOld Power House Road, Ramnagar, Gondia, Maharashtra, IndiaVarious approaches have been used to retain the dosage form in the stomach as a way of increasing the gastric residence time (GRT), including floatation systems; high-density systems; mucoadhesive systems; magnetic systems; unfoldable, extendible, or swellable systems;...

  5. 阿卡波糖或吡格列酮+二甲双胍对单用二甲双胍控制不佳的2型糖尿病合并精神分裂症患者的疗效分析%Curative effect analysis of acarbose or pioglitazone + metformin in the treatment of type 2 diabetes mellitus complicated with schizophrenia under poor metformin monotherapy control

    Institute of Scientific and Technical Information of China (English)

    周艳兰; 陈新河; 刘艳萍; 陈钊; 严玲

    2015-01-01

    Objective To compare the curative effect and safety of acarbose or pioglitazone in the treatment of type 2 diabetes mellitus complicated with schizophrenia under poor metformin monotherapy control. Methods A total of 103 patients of type 2 diabetes mellitus complicated with schizophrenia under poor metformin monotherapy control were randomly divided into acarbose group with 52 cases and pioglitazone group with 51 cases. The acarbose group received metformin+acarbose for treatment, and the pioglitazone group received metformin+pioglitazone. Treatment lasted for 24 weeks. Blood glucose and blood lipid were detected before and after treatment in the two groups, and their body mass and blood pressure were recorded. Adverse reactions as hypoglycemia were recorded for comparison.Results After treatment, both groups had lower fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) than those before treatment (P0.05).Conclusion Implement of acarbose or pioglitazone can effectively control blood glucose with high safety in the treatment of type 2 diabetes mellitus complicated with schizophrenia under poor metformin monotherapy control. Acarbose provides better effect in reducing 2 h PG than pioglitazone, while pioglitazone’s effect in reducing FPG is better than acarbose.%目的:比较2型糖尿病合并精神分裂症患者单用二甲双胍血糖控制不佳时加用阿卡波糖或吡格列酮的疗效和安全性。方法103例单用二甲双胍血糖控制不佳的2型糖尿病合并精神分裂症患者随机分为阿卡波糖组52例和吡格列酮组51例。阿卡波糖组采用二甲双胍+阿卡波糖治疗,吡格列酮组采用二甲双胍+吡格列酮治疗,疗程均为24周。两组治疗前后检测血糖、血脂指标,测量体质量和血压,记录低血糖等不良反应情况并进行对比。结果疗程结束后,两组空腹血糖(FPG)、糖化血红蛋白(HbA1c)均低于治疗前(P0.05)。结论单用二

  6. Anti-diabetes drug pioglitazone ameliorates synaptic defects in AD transgenic mice by inhibiting cyclin-dependent kinase5 activity.

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    Jinan Chen

    Full Text Available Cyclin-dependent kinase 5 (Cdk5 is a serine/threonine kinase that is activated by the neuron specific activators p35/p39 and plays many important roles in neuronal development. However, aberrant activation of Cdk5 is believed to be associated with the pathogenesis of several neurodegenerative diseases, including Alzheimer's disease (AD and Parkinson's disease (PD. Here in the present study, enhanced Cdk5 activity was observed in mouse models of AD; whereas soluble amyloid-β oligomers (Aβ, which contribute to synaptic failures during AD pathogenesis, induced Cdk5 hyperactivation in cultured hippocampal neurons. Inhibition of Cdk5 activity by pharmacological or genetic approaches reversed dendritic spine loss caused by soluble amyloid-β oligomers (Aβ treatment. Interestingly, we found that the anti-diabetes drug pioglitazone could inhibit Cdk5 activity by decreasing p35 protein level. More importantly, pioglitazone treatment corrected long-term potentiation (LTP deficit caused by Aβ exposure in cultured slices and pioglitazone administration rescued impaired LTP and spatial memory in AD mouse models. Taken together, our study describes an unanticipated role of pioglitazone in alleviating AD and reveals a potential therapeutic drug for AD curing.

  7. Alternative Agents in Type 1 Diabetes in Addition to Insulin Therapy: Metformin, Alpha-Glucosidase Inhibitors, Pioglitazone, GLP-1 Agonists, DPP-IV Inhibitors, and SGLT-2 Inhibitors.

    Science.gov (United States)

    DeGeeter, Michelle; Williamson, Bobbie

    2016-04-01

    Insulin is the mainstay of current treatment for patients with type 1 diabetes mellitus (T1DM). Due to increasing insulin resistance, insulin doses are often continually increased, which may result in weight gain for patients. Medications currently approved for the treatment of type 2 diabetes offer varying mechanisms of action that can help to reduce insulin resistance and prevent or deter weight gain. A MEDLINE search was conducted to review literature evaluating the use of metformin, alpha-glucosidase inhibitors, pioglitazone, glucagon-like peptide 1 agonists, dipeptidyl peptidase, and sodium-dependent glucose transporter 2 inhibitors, in patients with T1DM. Varying results were found with some benefits including reductions in hemoglobin A1c, decreased insulin doses, and favorable effects on weight. Of significance, a common fear of utilizing multiple therapies for diabetes treatment is the risk of hypoglycemia, and this review displayed limited evidence of hypoglycemia with multiple agents.

  8. Improvement of cardiovascular risk markers by pioglitazone is independent from glycemic control - Results from the pioneer study

    NARCIS (Netherlands)

    Pfutzner, A; Marx, N; Lubben, G; Langenfeld, M; Walcher, D; Konrad, T; Forst, T

    2005-01-01

    OBJECTIVES This study was performed to assess whether the anti-inflammatory and antiatherogenic effects of pioglitazone suggested by animal experiments are reproducible in man and independent from improvements in metabolic control. BACKGROUND Type 2 diabetes is associated with increased cardiovascul

  9. Protective effect of pioglitazone, a PPARγ agonist against acetaminophen-induced hepatotoxicity in rats.

    Science.gov (United States)

    Gupta, Gaurav; Krishna, Gopala; Chellappan, Dinesh Kumar; Gubbiyappa, Kumar Shiva; Candasamy, Mayuren; Dua, Kamal

    2014-08-01

    Acetaminophen has a reasonable safety profile when consumed in therapeutic doses. However, it could induce hepatotoxicity and even acute liver failure when taken at an overdose. Pioglitazone, PPARγ ligand, is clinically tested and used in treatment of diabetes. PPARγ is a key nuclear hormone receptor of lipid metabolisms and regulates several gene transcriptions associated with differentiation, growth arrest, and apoptosis. The aim of our study was to evaluate the hepatoprotective activity of pioglitazone on acetaminophen-induced hepatotoxicity and to understand the relationship between the PPARγ and acetaminophen-induced hepato injury. For the experiment, Sprague-Dawley rats (160-180 g) were used and divided into four groups. Groups I and II were normal and experimental controls, respectively. Groups III and IV received the pioglitazone 20 mg/kg for 10 days. Hepatotoxicity was induced in Groups II and III on the eighth day with acetaminophen (i.p. 350 mg/kg body weight). The hepatoprotective effect was evaluated by performing an assay of the total protein, total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and α-fetoprotein as well as glutathione peroxidase, lipid peroxidation, catalase, superoxide dismutase, and glutathione transferase and liver histopathology. The assay results were presented as mean and standard error of mean for each group. The study group was compared with the control group by one-way ANOVA test. A p value of hepatotoxicity. Liver histopathological examination showed that pioglitazone administration antagonized acetaminophen -induced liver pathological damage. Various biochemical estimations of different hepatic markers and antioxidant enzymes and histopathological studies of liver tissues glimpse a support to its significant hepatoprotective activity on acetaminophen -induced hepatotoxicity.

  10. The Peroxisome Proliferator Activated Receptor‐γ Pioglitazone Improves Vascular Function and Decreases Disease Activity in Patients With Rheumatoid Arthritis

    Science.gov (United States)

    Marder, Wendy; Khalatbari, Shokoufeh; Myles, James D.; Hench, Rita; Lustig, Susan; Yalavarthi, Srilakshmi; Parameswaran, Aishwarya; Brook, Robert D.; Kaplan, Mariana J.

    2013-01-01

    Background Rheumatoid arthritis (RA) is associated with heightened mortality due to atherosclerotic cardiovascular disease (CVD). Inflammatory pathways in RA negatively affect vascular physiology and promote metabolic disturbances that contribute to CVD. We hypothesized that the peroxisome proliferator activated receptor‐γ (PPAR‐γ) pioglitazone could promote potent vasculoprotective and anti‐inflammatory effects in RA. Methods and Results One hundred forty‐three non‐diabetic adult RA patients (76.2% female, age 55.2±12.1 [mean±SD]) on stable RA standard of care treatment were enrolled in a randomized, double‐blind placebo controlled crossover trial of 45 mg daily pioglitazone versus placebo, with a 3‐month duration/arm and a 2‐month washout period. Pulse wave velocity of the aorta (PWV), brachial artery flow mediated dilatation (FMD), nitroglycerin mediated dilatation (NMD), microvascular endothelial function (reactive hyperemia index [RHI]), and circulating biomarkers of inflammation, insulin resistance, and atherosclerosis risk all were quantified. RA disease activity was assessed with the 28‐Joint Count Disease Activity Score (DAS‐28) C‐reactive protein (CRP) and the Short Form (36) Health Survey quality of life questionnaire. When added to standard of care RA treatment, pioglitazone significantly decreased pulse wave velocity (ie, aortic stiffness) (P=0.01), while FMD and RHI remained unchanged when compared to treatment with placebo. Further, pioglitazone significantly reduced RA disease activity (P=0.02) and CRP levels (P=0.001), while improving lipid profiles. The drug was well tolerated. Conclusions Addition of pioglitazone to RA standard of care significantly improves aortic elasticity and decreases inflammation and disease activity with minimal safety issues. The clinical implications of these findings remain to be established. Clinical Trial Registration URL: ClinicalTrials.gov Unique Identifier: NCT00554853. PMID:24252844

  11. Observation on the effect of Glargine combined with Metformin and/or pioglitazone in treatment for the newly diagnosed type 2 diabetes%甘精胰岛素联合二甲双胍或/和吡格列酮治疗初诊2型糖尿病疗效观察

    Institute of Scientific and Technical Information of China (English)

    全会标; 高勇义

    2012-01-01

    OBJECTIVE To compare the clinical effects and safety of treating newly diagnosed type 2diabetes patients by combining Glargine with Metformin or/and pioglitazone. METHODS 98 cases with newly diagnosed type 2 diabetes, who had poorly controlled blood glucose with Metformin at least four weeks, were randomly divided into three groups. Glargine plus Metformin were used in group A. Glargine plus pioglitazone were used in group B, and glargine plus pioglitazone and metformin were used in Group C. All three groups were given a 12-week follow-up. RESULTS FPG of patients was all up to the standard, and 2hPG and HbAlc levels were lower in the patients after treatment (P 0.05). In all three groups, no severe hypoglycemia occurred. CONCLUSION The method of combining Glargine with Metformin and pioglitazone could effectively control blood sugar of the newly diagnosed type 2 diabetes patients. Moreover, the incidence of low blood sugar was lower.lt would be the ideal method to treat newly diagnosed type 2 diabetes patients considering the general safety and effectiveness.%目的 比较甘精胰岛素联合二甲双胍或/和吡格列酮治疗初诊2型糖尿病(T2DM)的疗效及安全性.方法 初诊T2DM先单用二甲双胍(1.0 g/d)治疗4周,血糖控制不佳的98例患者随机分为3组.A组:二甲双胍+甘精胰岛素,B组:吡格列酮+甘精胰岛素,C组:二甲双胍+吡格列酮+甘精胰岛素,治疗随访12周.结果 12周后3组患者的空腹血糖(FPG)全部达标,餐后2h血糖(2hPG)、糖化血红蛋白(HbA1c)均比治疗前明显降低,A、B两组HbA1c部分达标,C组HbA1c达标(P<0.05).C组疗效优于A、B组,FPG达标所需时间最短,日胰岛素用量最少.3组低血糖发生率均<3.5%,无严重低血糖,差异无统计学意义(P>0.05).结论 甘精胰岛素联合二甲双胍或/和吡格列酮均能较好地控制血糖,低血糖发生率低,三药联合疗效优于二药联合,安全有效是初诊T2DM理想的治疗方案.

  12. Combination Therapy with Losartan and Pioglitazone Additively Reduces Renal Oxidative and Nitrative Stress Induced by Chronic High Fat, Sucrose, and Sodium Intake

    Directory of Open Access Journals (Sweden)

    Xiang Kong

    2012-01-01

    Full Text Available We recently showed that combination therapy with losartan and pioglitazone provided synergistic effects compared with monotherapy in improving lesions of renal structure and function in Sprague-Dawley rats fed with a high-fat, high-sodium diet and 20% sucrose solution. This study was designed to explore the underlying mechanisms of additive renoprotection provided by combination therapy. Losartan, pioglitazone, and their combination were orally administered for 8 weeks. The increased level of renal malondialdehyde and expression of nicotinamide adenine dinucleotide phosphate oxidase subunit p47phox and nitrotyrosine as well as the decreased total superoxide dismutase activity and copper, zinc-superoxide dismutase expression were tangible evidence for the presence of oxidative and nitrative stress in the kidney of model rats. Treatment with both drugs, individually and in combination, improved these abnormal changes. Combination therapy showed synergistic effects in reducing malondialdehyde level, p47phox, and nitrotyrosine expression to almost the normal level compared with monotherapy. All these results suggest that the additive renoprotection provided by combination therapy might be attributed to a further reduction of oxidative and nitrative stress.

  13. Effects of pioglitazone mediated activation of PPAR-γ on CIDEC and obesity related changes in mice.

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    Bilal Haider Shamsi

    Full Text Available OBJECTIVE: Obesity is a metabolic disorder that can lead to high blood pressure, increased blood cholesterol and triglycerides, insulin resistance, and diabetes mellitus. The aim was to study the effects of pioglitazone mediated sensitization of peroxisome proliferator-activated receptor gamma (PPAR-γ on the relationship of Cell death-inducing DFFA-like effector C (CIDEC with obesity related changes in mice. METHODS: Sixty C57B/L6 mice weighing 10-12g at 3 weeks of age were randomly divided into 3 groups. Mice in Group 1 were fed on normal diet (ND while Group 2 mice were given high fat diet (HFD, and Group 3 mice were given high fat diet and treated with Pioglitazone (HFD+P. Body weight, length and level of blood sugar were measured weekly. Quantitative real-time PCR, fluorescence microscopy, and ELISA were performed to analyze the expression of CIDEC and PPAR-γ in visceral adipose tissue (VAT and subcutaneous adipose tissue (SAT. RESULTS: Body weight and length of mice increased gradually with time in all groups. Blood sugar in HFD mice started to increase significantly from the mid of late phase of obesity while pioglitazone attenuated blood sugar level in HFD+P mice. The mRNA expressions and protein levels of PPAR-γ and CIDEC genes started to increase in HFD mice as compared to ND mice and decreased gradually during the late phase of obesity in VAT. Pioglitazone enhanced the expression of PPAR-γ and CIDEC genes in HFD+P mice even during the late phase of obesity. CONCLUSION: It is insinuated that VAT is associated with late phase obesity CIDEC decrease and insulin resistance, while pioglitazone enhances CIDEC through activation of PPAR-γ, increases its expression, and decreases lipolysis, hence preventing an increase of blood sugar in mice exposed to HFD.

  14. An experimental study of pioglitazone in treating vascular dementia

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To compare the therapeutic effects of different doses of pioglitazone,a kind of peroxisome proliferator-activated receptor γ(PPARγ)agonist,on vascular dementia and explore how pioglitazone affects cerebral ischemia.Methods Modified Pulsinelli's vessel ligation was used to establish a vascular dementia model in rats.Recognition,learning and memory were evaluated by Morris's water maze test.Immunoenzyme staining was used to determine the number of nerve cells.Immunofluorescence double-staining was u...

  15. Different effects of thiazolidinediones on cardiovascular risk in patients with type 2 diabetes mellitus: pioglitazone versus rosiglitazone.

    Science.gov (United States)

    Simó, R; Rodriguez, A; Caveda, E

    2010-07-02

    Cardiovascular disease remains the primary cause of mortality for patients with type 2 diabetes, which is characterized by insulin resistance. The thiazolidinediones (TZDs), also known as glitazones, are one of the pharmacological approaches to improve insulin sensitivity. At present, there are two available TZDs: pioglitazone and rosiglitazone. The common target of action for TZDs is the nuclear peroxisome proliferator-activated receptor-gamma (PPAR-gamma) that regulates the gene transcription involved in adipocyte differentiation and glucose and lipid metabolism. TZDs have shown similar effects on glycemic control, as well as on weight gain, fluid retention, increased risk of heart failure, and leg and forearm fractures. However, TZDs have differential effects on cardiovascular disease. This article will review the differential effects of pioglitazone and rosiglitazone on cardiovascular risk factors and outcomes, as well as the potential differences between them. Based upon available evidence, pioglitazone has a beneficial effect on cardiovascular disease. By contrast, it seems that rosiglitazone increases cardiovascular risk. The difference in lipid profile may be the main factor accounting for the superiority of pioglitazone in reducing cardiovascular risk.

  16. FORMULATION AND EVALUATION OF MUCOADHESIVE MICROSPHERES OF PIOGLITAZONE HYDROCHLORIDE USING A NATURAL POLYMER

    Directory of Open Access Journals (Sweden)

    Mobeen Mohd.

    2015-04-01

    Full Text Available The objective of the present investigation was to design a controlled release dosage form for a thiazolidinedione oral hypoglycemic drug i.e., pioglitazone hydrochloride employing a natural polymer. The present study was also aimed to increase the biological half-life by developing it in the form of sustained release microspheres. The present study aimed at employing a natural polymer in formulating the mucoadhesive microspheres and estimate its effect over the controlled release of the drug from the formulation. The microspheres of pioglitazone hydrochloride were prepared by employing sodium alginate as a cell forming polymer and by using a natural bio-adhesive polymer viz. goru gum in the ratios of 1:1, 1:1.5 and 1:2, by orifice ion gelation method with varying concentrations of calcium chloride. Six batches of microspheres (MS1 – MS6 were prepared. The microspheres were evaluated for various micromeritic properties and it was observed that all the batches exhibited free-flowing properties. Scanning electron microscopy results showed that the microspheres were almost spherical in shape and discrete. The FTIR results showed that there were no interactions between the drug and the excipients. The in vitro release profile indicated that all the batches of microspheres showed controlled and prolonged drug release over an extended period, with acceptable release kinetics. The work demonstrated that among all the formulations of microspheres, the microspheres of the formulation MS4 are promising candidates for the sustained release of pioglitazone hydrochloride.

  17. Pioglitazone use and the risk of bladder cancer.

    Science.gov (United States)

    Kuo, Hsin-Wei; Tiao, Mao-Meng; Ho, Shu-Chen; Yang, Chun-Yuh

    2014-02-01

    This study aimed to identify the risk association between pioglitazone exposure and bladder cancer. A nested case-control study was performed using a representative database randomly sampled from National Health Insurance enrollees. The source cohort consisted of newly diagnosed diabetic patients from 1997 to 2009. Cases were identified as those with a diagnosis of bladder cancer from 2002 to 2009. For each case, four matched control individuals were randomly selected. A multiple logistic regression model was used to estimate the relative magnitude of risk in relation to the use of pioglitazone. In total, 259 cases and 1036 controls were identified. The prevalent use of pioglitazone is similar in cases and controls (adjusted odds ratio, 1.20; 95% confidence interval, 0.58-2.49). Compared to nonusers, these values were 1.08 (0.41-2.88) for those with cumulative pioglitazone use ≤ 8268 mg and 1.35 (0.48-3.79) for those with cumulative pioglitazone use > 8268 mg. This study does not provide support for the risk association between pioglitazone exposure and bladder cancer. Further confirmation is needed due to the limitation of small case number with relatively shorter exposure duration and lower cumulative dose.

  18. The Effectiveness of Liraglutide in Nonalcoholic Fatty Liver Disease Patients with Type 2 Diabetes Mellitus Compared to Sitagliptin and Pioglitazone

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    Takamasa Ohki

    2012-01-01

    Full Text Available Background. Liraglutide leading to improve not only glycaemic control but also liver inflammation in non-alcoholic fatty liver disease (NAFLD patients. Aims. The aim of this study is to elucidate the effectiveness of liraglutide in NAFLD patients with type 2 diabetes mellitus (T2DM compared to sitagliptin and pioglitazone. Methods. We retrospectively enrolled 82 Japanese NAFLD patients with T2DM and divided into three groups (liraglutide: N = 26, sitagliptin; N = 36, pioglitazone; N = 20. We compared the baseline characteristics, changes of laboratory data and body weight. Results. At the end of follow-up, ALT, fast blood glucose, and HbA1c level significantly improved among the three groups. AST to platelet ratio significantly decreased in liraglutide group and pioglitazone group. The body weight significantly decreased in liraglutide group (81.8 kg to 78.0 kg, <0.01. On the other hands, the body weight significantly increased in pioglitazone group and did not change in sitagliptin group. Multivariate regression analysis indicated that administration of liraglutide as an independent factor of body weight reduction for more than 5% (OR 9.04; 95% CI 1.12–73.1, =0.04. Conclusions. Administration of liraglutide improved T2DM but also improvement of liver inflammation, alteration of liver fibrosis, and reduction of body weight.

  19. The effects of polysaccharides and pioglitazone on mouse model of pulmonary adenocarcinoma%植物多糖和吡格列酮对小鼠肺腺癌干预效果的研究

    Institute of Scientific and Technical Information of China (English)

    邓增华; 谢辉; 陈振岗; 王广舜; 张成岗

    2015-01-01

    Objective To provide theoretical reference for clinical therapy of pulmonary adenocarcinoma by evaluating the effects of polysaccharides and pioglitazone on mouse model of pulmonary adenocarcinoma and to explore the relationship between inflammation and pulmonary adenocarcinoma. Methods One hundred mice were averagely divided into five groups, including control group, model group, polysaccharides group, pioglitazone group, polysaccharides and pioglitazone group (unite group). Polysaccharides solution (500 mg/kg) was given to polysaccharides group, pioglitazone solution (15 mg/kg) was given to pioglitazone group, polysaccharides solution (500 mg/kg) and pioglitazone solution (15 mg/kg) were given to unite group;and the equal volume of saline (10 mL/kg) was given to control and model group (1 t/d, 5 d/w, continuously 20 w ). The pulmonary adenocarcinoma induced by urethane was evaluated in each group at different time points. The levels of NF-κB, TNF-α, IL-1β and IL-6 were measured in each group at the 12th week and the 20th week respectively. Results The body weights were increased in the control group, which were decreased in other groups during urethane-injection, but increased continuously after the injection. At the 20th week, nodules were found in lung surfaces in all mice except mice of control group. The lung index was higher in all mice except mice of control group. The levels of NF-κB, TNF-α, IL-1βand IL-6 were significantly higher at 12th week and 20th in model group, polysaccharides group, pioglitazone group, polysaccha⁃rides and pioglitazone group than those of control group. The levels of NF-κB, TNF-α, IL-1βand IL-6 were significantly lower in polysaccharides group, pioglitazone group, polysaccharides and pioglitazone group than those of model group. Con⁃clusion Sustained inflammatory response is one of the risk factors for the development of lung adenocarcinoma. Polysaccha⁃rides and pioglitazone can reduce the level of inflammation in

  20. Pioglitazone, a PPARγ agonist rescues depression associated with obesity using chronic unpredictable mild stress model in experimental mice.

    Science.gov (United States)

    Kurhe, Yeshwant; Mahesh, Radhakrishnan

    2016-06-01

    Pioglitazone, a peroxisome proliferator activated receptor gamma (PPARγ) agonist belonging to thiazolidinedione class, is mainly used in diabetes mellitus. Obese subjects are twice likely to become depressed than non-obese individuals. The biological mechanisms linking depression with obesity still remain poorly understood and there is immense need for better therapeutic intervention against such co-morbid disorders. The present study investigates the effect of pioglitazone on the chronic unpredictable mild stress (CUMS) induced depression in obese mice by using behavioral tests and biochemical estimations. Mice were fed with high fat diet (HFD) for 14 weeks and were further subjected to different stress procedures for 28 days to induce depressive behavior. Animals were administered orally with pioglitazone (30 mg/kg p.o.)/escitalopram (10 mg/kg p.o.)/vehicle (10 ml/kg p.o.) daily from day 15-28. Various behavioral paradigms such as sucrose preference test, forced swim test (FST), tail suspension test (TST) and elevated plus maze (EPM) were performed. Biochemical estimations including plasma glucose, total cholesterol, triglycerides, and total proteins were performed. The data obtained from behavioral assays and biochemical assessments indicated that obese animals exhibited severe depressive-like behavior compared to non-obese animals. Furthermore, obese animals subjected to CUMS worsen the depressive behavior compared to obese control animals. Repetitive treatment with pioglitazone reversed the CUMS induced behavioral and biochemical alterations in HFD fed obese mice which atleast in part may be mediated through improving altered plasma glucose. The study suggests that pioglitazone needs further attention with respect to molecular mechanisms that could provide a better therapeutic strategy against depression associated with obesity.

  1. Pioglitazone, a PPARγ agonist rescues depression associated with obesity using chronic unpredictable mild stress model in experimental mice

    Directory of Open Access Journals (Sweden)

    Yeshwant Kurhe

    2016-06-01

    Full Text Available Pioglitazone, a peroxisome proliferator activated receptor gamma (PPARγ agonist belonging to thiazolidinedione class, is mainly used in diabetes mellitus. Obese subjects are twice likely to become depressed than non-obese individuals. The biological mechanisms linking depression with obesity still remain poorly understood and there is immense need for better therapeutic intervention against such co-morbid disorders. The present study investigates the effect of pioglitazone on the chronic unpredictable mild stress (CUMS induced depression in obese mice by using behavioral tests and biochemical estimations. Mice were fed with high fat diet (HFD for 14 weeks and were further subjected to different stress procedures for 28 days to induce depressive behavior. Animals were administered orally with pioglitazone (30 mg/kg p.o./escitalopram (10 mg/kg p.o./vehicle (10 ml/kg p.o. daily from day 15–28. Various behavioral paradigms such as sucrose preference test, forced swim test (FST, tail suspension test (TST and elevated plus maze (EPM were performed. Biochemical estimations including plasma glucose, total cholesterol, triglycerides, and total proteins were performed. The data obtained from behavioral assays and biochemical assessments indicated that obese animals exhibited severe depressive-like behavior compared to non-obese animals. Furthermore, obese animals subjected to CUMS worsen the depressive behavior compared to obese control animals. Repetitive treatment with pioglitazone reversed the CUMS induced behavioral and biochemical alterations in HFD fed obese mice which atleast in part may be mediated through improving altered plasma glucose. The study suggests that pioglitazone needs further attention with respect to molecular mechanisms that could provide a better therapeutic strategy against depression associated with obesity.

  2. The PPAR-γ agonist pioglitazone modulates inflammation and induces neuroprotection in parkinsonian monkeys

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    Swanson Christine R

    2011-08-01

    Full Text Available Abstract Background Activation of the peroxisome proliferator-activated receptor gamma (PPAR-γ has been proposed as a possible neuroprotective strategy to slow down the progression of early Parkinson's disease (PD. Here we report preclinical data on the use of the PPAR-γ agonist pioglitazone (Actos®; Takeda Pharmaceuticals Ltd. in a paradigm resembling early PD in nonhuman primates. Methods Rhesus monkeys that were trained to perform a battery of behavioral tests received a single intracarotid arterial injection of 20 ml of saline containing 3 mg of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP. Twenty-four hours later the monkeys were assessed using a clinical rating scale, matched accordingly to disability, randomly assigned to one of three groups [placebo (n = 5, 2.5 (n = 6 or 5 (n = 5 mg/kg of pioglitazone] and their treatments started. Three months after daily oral dosing, the animals were necropsied. Results We observed significant improvements in clinical rating score (P = 0.02 in the animals treated with 5 mg/kg compared to placebo. Behavioral recovery was associated with preservation of nigrostriatal dopaminergic markers, observed as higher tyrosine hydroxylase (TH putaminal optical density (P = 0.011, higher stereological cell counts of TH-ir (P = 0.02 and vesicular monoamine transporter-2 (VMAT-2-ir nigral neurons (P = 0.006. Stereological cell counts of Nissl stained nigral neurons confirmed neuroprotection (P = 0.017. Pioglitazone-treated monkeys also showed a dose-dependent modulation of CD68-ir inflammatory cells, that was significantly decreased for 5 mg/kg treated animals compared to placebo (P = 0.018. A separate experiment to assess CSF penetration of pioglitazone revealed that 5 mg/kg p.o. induced consistently higher levels than 2.5 mg/kg and 7.5 mg/kg. p.o. Conclusions Our results indicate that oral administration of pioglitazone is neuroprotective when administered early after inducing a

  3. Efficacy of pioglitazone on glycemic control and carotid intima-media thickness in type 2 diabetes patients with inadequate insulin therapy.

    Science.gov (United States)

    Yasunari, Eisuke; Takeno, Kageumi; Funayama, Hideaki; Tomioka, Setsuko; Tamaki, Motoyuki; Fujitani, Yoshio; Kawamori, Ryuzo; Watada, Hirotaka; Hirose, Takahisa

    2011-01-24

    Aims/Introduction:  The present study was designed to determine the effects of pioglitazone on glycemic control and atherosclerosis in patients with poorly controlled type 2 diabetes on insulin therapy.   The study was a prospective, randomized controlled trial involving 48 patients with inadequately controlled type 2 diabetes treated with insulin. We assigned patients to oral pioglitazone titrated from 15-30 mg (n = 22) or no pioglitazone (n = 26), to be taken in addition to their glucose-lowering drugs and other medications. Daily insulin doses and numbers were recorded during the study period.   The adjusted mean glycosylated hemoglobin (HbA1c) values decreased significantly by 1.13 ± 1.50% and 0.55 ± 0.76% in the pioglitazone and control groups, respectively. Significant decrease of HbA1c level was observed in the pioglitazone group compared with the control group (P < 0.05). The insulin dose lowered by 0.04 ± 0.10 units/kg/day in the pioglitazone group and increased by 0.03 ± 0.10 units/kg/day in the control group (P < 0.05). The number of insulin injections decreased by 0.1 ± 0.6 times/day in the pioglitazone group and increased by 0.2 ± 0.4 times/day in the control group (P < 0.05). The carotid intima-media thickness estimated by B-mode echography was carried out in both groups and decreased significantly at the end-point only in the pioglitazone group, relative to the baseline.   These findings show that pioglitazone is useful in improving glycemic control and preventing the progression of atherosclerosis in poorly-controlled type 2 diabetics on insulin therapy. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00064.x, 2010).

  4. Anti-diabetic properties of a non-conventional radical scavenger, as compared to pioglitazone and exendin-4, in streptozotocin-nicotinamide diabetic mice.

    Science.gov (United States)

    Novelli, Michela; Canistro, Donatella; Martano, Manuela; Funel, Niccola; Sapone, Andrea; Melega, Simone; Masini, Matilde; De Tata, Vincenzo; Pippa, Anna; Vecoli, Cecilia; Campani, Daniela; De Siena, Rocco; Soleti, Antonio; Paolini, Moreno; Masiello, Pellegrino

    2014-04-15

    We previously showed that the innovative radical scavenger bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC) improves metabolic dysfunctions in a diabetic mouse model. Here, we compared the in vivo effects of IAC with those of the anti-diabetic drugs pioglitazone (PIO) and exendin-4 (EX-4). Diabetes was induced in C57Bl/6J mice by streptozotocin and nicotinamide administration. Paralleled by healthy controls, diabetic animals (D) were randomly assigned to four groups and treated daily for 7 consecutive weeks: D+saline, ip; D+IAC 30mg/kgb.w., ip; D+PIO 10mg/kgb.w. per os; and D+EX-4, 50μg/kgb.w., ip. Our results show that IAC reduced basal hyperglycemia and improved glucose tolerance better than PIO or EX-4. Interestingly, in the heart of diabetic mice, IAC treatment normalized the increased levels of GSSG/GSH ratio and thiobarbituric acid reactive substances, indexes of oxidative stress and damage, while PIO and EX-4 were less effective. As supported by immunohistochemical data, IAC markedly prevented diabetic islet β-cell reduced density, differently from PIO and EX-4 that had only a moderate effect. Interestingly, in diabetic animals, IAC treatment enhanced the activity of pancreatic-duodenal homeobox 1 (PDX-1), an oxidative stress-sensitive transcription factor essential for maintenance of β-cell function, as evaluated by quantification of its nuclear immunostaining, whereas PIO or EX-4 treatments did not. Altogether, these observations support the improvement of the general redox balance and β-cell function induced by IAC treatment in streptozotocin-nicotinamide diabetic mice. Furthermore, in this model, the correction of diabetic alterations was better obtained by treatment with the radical scavenger IAC than with pioglitazone or exendin-4.

  5. Research on the protection effect of pioglitazone for non-alcoholic fatty liver disease (NAFLD) in rats

    Institute of Scientific and Technical Information of China (English)

    XU Ping; ZHANG Xing-guo; LI You-ming; YU Chao-hui; XU Lei; XU Gen-yun

    2006-01-01

    Objective: The prevalence of non-alcoholic fatty liver disease (NAFLD) has markedly increased. Insulin resistance has been implicated in the pathogenesis of NAFLD. This study was aimed at observing the relationship between insulin resistance and NAFLD, and evaluating the role of pioglitazone (PGZ) acting as insulin-sensitizing agents in the prevention and treatment of rat fatty liver induced by high fat feeding. Methods: The rats were separated randomly into 6 groups: model group I were fed high simultaneous with high fat diet for 8 weeks after high fat feeding for 8 weeks, control group Ⅱ were fed normal food for 16 weeks.The rats were sacrificed after 8 weeks and 16 weeks respectively. Liver weight, body weight, serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), tumor necrosis factor alpha (TNL-α), fasting blood glucose (FBG), fasting plasma insulin (FINS), HOMA (homeostasis model assessment) insulin resistance index (HOMA-IR), and the liver histology of rats of all groups were assayed. Results: After 8 weeks, the liver in model group I showed typical steatosis, accompanied with mild to moderate lobular inflammatory cell infiltration, liver indexes and serum levels of ALT,AST, ALP, TNF-α were significantly increased (P<0.05) compared with control group I. Whereas, the degree of hepatic injury was attenuated in PGZ prevention group, liver indexes and serum levels of ALT, ALP were significantly decreased (P<0.05)compared with model group Ⅰ. After 16 weeks, notable steatosis, and lobular inflammation were observed in model group Ⅱ rat liver, while the degree of hepatic injury was attenuated in the PGZ treatment group. Liver index, serum levels of ALT, AST, ALP,FINS and HOMA-IR were significantly increased (P<0.05) in model group Ⅱ compared with control group Ⅱ. Whereas, in PGZ treatment group, serum levels of AST and FINS showed decreasing tendency, liver indexes, serum levels of ALT

  6. Effect of pioglitazone and metformin on visfatin in obese patients with newly diagnosed type 2 diabetes mellitus%吡格列酮与二甲双胍对初诊肥胖2型糖尿病患者血清内脏脂肪素影响的研究

    Institute of Scientific and Technical Information of China (English)

    陈育; 黄贵心; 黄家庆; 黄晓君

    2009-01-01

    Objective To research the effects of pioglitazone or metformin on visfatin in obese patients with type 2 diabetes mellitus.Methods 100 type 2 diabetic obese patients were treated for 24 weeks and randomized into two groups. The subjects in pioglitazone group received piolitazone 30 mg daily. The subjects in metformin group received metformin 500 mg twice daily.Results After treatment with pioglitazone, the fasting plasma visfatin,the insulin resistance and triglyceride were decreased(P<0.01,<0.05,<0.05 respectively), and HOMA-β was increased(P<0.05). The levels of visfatin and triglyceride in the metformin group were not changed(P>0.05). Meanwhile,in pioglitazone group, the visfatin,insulin resistance and triglyceride were decreased obviously, and the function of β-cell was somewhat improved, which did not occur in metformin group.But the body mass index was more decreased in metformin group than in pioglitazone group(P<0.05). Conclusions Both pioglitazone and metformin can decrease the fasting plasma glucose and glycosylated hemoglobin. Also, pioglitazone can decrease the blood visfatin,which shows that pioglitazone has anti-inflammatory effects and can interfere the development of type 2 diabetes mellitus.%目的 观察吡格列酮与二甲双胍对初诊肥胖T2DM患者血清内脏脂肪素(visfatin)水平的影响,探讨visfatin与T2DM发病的关系和药物的治疗机制.方法 100例初诊肥胖T2DM患者随机分为吡格列酮组50例,每日口服盐酸吡格列酮片30mg,二甲双胍组50例,每日早晚口服二甲双胍缓释片500mg,疗程24周.结果 吡格列酮组空腹血清visfatin、IR、TG较用药前明显降低,β细胞功能有改善(P<0.05或P<0.01).二甲双胍组血清visfatin、TG无统计学改变.两组治疗后比较,吡格列酮组的visfatin、IR、TG降低明显,差异有统计学意义(P<0.05或<0.01),但二甲双胍组的BMI较吡格列酮组下降更明显(P<0.05).结论 对初诊肥胖T2DM患者吡

  7. Spectrophotometric estimation of pioglitazone hydrochloride in tablet dosage form

    Directory of Open Access Journals (Sweden)

    Basniwal Pawan

    2008-01-01

    Full Text Available Two simple, rapid, and precise methods - linear regression equation (LRE and standard absorptivity - were developed and validated for the estimation of pioglitazone hydrochloride in tablet dosage form. The maximum absorbance (lmax of pioglitazone hydrochloride was found to be 269.8 nm in methanol:water:hydrochloric acid (250:250:1. Beer-Lambert law was obeyed in the concentration range of 10-50 µg/ml, and the standard absorptivity was found to be 253.97 dl/g/cm. Both the methods were validated for linearity, accuracy, precision (days, analysts, and instrument variation, and robustness (solvent composition. The numerical values for all parameters lie within the acceptable limits. Pioglitazone hydrochloride was estimated in the range of 99.58-99.97% by LRE method and 100.25-100.75% by standard absorptivity method. At 99% confidence limit, the F-test value for the methods was found to be 1.8767.

  8. Protective effects of pioglitazone and/or liraglutide on pancreatic β-cells in db/db mice: Comparison of their effects between in an early and advanced stage of diabetes.

    Science.gov (United States)

    Kimura, Tomohiko; Kaneto, Hideaki; Shimoda, Masashi; Hirukawa, Hidenori; Okauchi, Seizo; Kohara, Kenji; Hamamoto, Sumiko; Tawaramoto, Kazuhito; Hashiramoto, Mitsuru; Kaku, Kohei

    2015-01-15

    The aim was to compare the protective effects of pioglitazone (PIO) and/or liraglutide (LIRA) on β-cells with the progression of diabetes. Male db/db mice were treated with PIO and/or LIRA for 2 weeks in an early and advanced stage. In an early stage insulin biosynthesis and secretion were markedly increased by PIO and LIRA which was not observed in an advanced stage. In concomitant with such phenomena, expression levels of various β-cell-related factors were up-regulated by PIO and LIRA only in an early stage. Furthermore, β-cell mass was also increased by the treatment only in an early stage. Although there was no difference in apoptosis ratio between the two stages, β-cell proliferation was augmented by the treatment only in an early stage. In conclusion, protective effects of pioglitazone and/or liraglutide on β-cells were more powerful in an early stage of diabetes compared to an advanced stage.

  9. The Adipose Tissue Endocrine Mechanism of the Prophylactic Protective Effect of Pioglitazone in High-Fat Diet-Induced Insulin Resistance

    National Research Council Canada - National Science Library

    Gong, Y; Li, J; Li, C; Mu, Y; Xiao, Y; Tian, H; Pan, C; Liu, Y

    2012-01-01

    ...), or a high-fat diet plus treatment with pioglitazone (P group). Glucose tolerance and insulin resistance were tested at weeks 10 and 11 after starting the diet and, at week 12, adipose, liver and skeletal muscle tissue samples were taken...

  10. Effect of Pioglitazone on Plasma Levels of Phenytoin in Rats

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    Abolghasem Jouyban

    2013-10-01

    Full Text Available Introduction: Interaction between drugs represents a major clinical concern for health care professionals and their patients. Patients affected by both type 2 diabetes and epilepsy may be prescribed pioglitazone and an anti-epileptic drug such as phenytoin  concurrently. The aim of this study was to consider the interaction of pioglitazone with phenytoin in an experimental model. According to the result of this study, concurrent use of phenytoin and pioglitazone in clinic may cause therapeutic failure of phenytoin which may cause seizures and during seizures the cardiac function may be affected. Material and Methods: Two groups of rats were treated for 30 days. In group 1 (control group saline (10 ml/kg and phenytoin   (30 mg/kg were administered daily by intragastric gavage. In group 2 (test group , pioglitazone (10 mg/kg was administered daily 60 minutes before phenytoin  (30 mg/kg. Two hours after the last intragastric gavage, animals were anesthetized with ether and 2 ml of blood was drawn from the heart into a syringe containing Ethylenediaminetetraacetic (EDTA, and phenytoin  concentration in rat plasma was determined by High performance liquid chromatography (HPLC.The study consisted of 2 groups of 10 male adult Wistar rats. Results: Compared with control group, concurrent use of pioglitazone and phenytoin   was associated with significantly lower mean plasma concentrations of phenytoin : 2.08 ± 0.03  µg/ml VS 1.2 ± 0.02  µg/ml. Conclusion: Concurrent use of pioglitazone and phenytoin was associated with a significant decrease in plasma concentration of phenytoin in this experimental model. In clinic, this interaction may cause seizures and it has been shown that both cardiac and respiratory functions may affected by seizures.

  11. Hypoglycaemia with oral antidiabetic drugs: results from prescription-event monitoring cohorts of rosiglitazone, pioglitazone, nateglinide and repaglinide.

    Science.gov (United States)

    Vlckova, Veronika; Cornelius, Victoria; Kasliwal, Rachna; Wilton, Lynda; Shakir, Saad A W

    2009-01-01

    Hypoglycaemia is an acute complication associated with intensive treatment of patients with diabetes mellitus. This complication poses a major challenge in diabetes management. Furthermore, severe hypoglycaemia may be life threatening. Although hypoglycaemia is more often associated with insulin treatment, oral hypoglycaemic agents have the potential to trigger hypoglycaemia. The aim of this study was to quantify the incidence of hypoglycaemic events and to describe the pattern of these incident events during the first 9 months of treatment with four oral antidiabetic drugs, rosiglitazone, pioglitazone, nateglinide and repaglinide, prescribed in general practice in England. We used data collected for prescription-event monitoring (PEM) studies of rosiglitazone, pioglitazone, nateglinide and repaglinide. PEM is an observational, non-interventional, incept cohort study. Observation time for each patient and incidence rate (IR) per 1000 patient-years of treatment for hypoglycaemia was calculated for each drug cohort. Smoothed hazard estimates were plotted over time. Case/non-case analysis was performed to describe and compare patients who had at least one hypoglycaemic event in the first 9 months of treatment with those who did not. The total number of patients included in the analysis was 14,373, 12,768, 4,549 and 5,727 in rosiglitazone, pioglitazone, nateglinide and repaglinide cohorts, respectively. From these, 276 patients experienced at least one episode of hypoglycaemia. The IR was between 50% and 100% higher in patients receiving treatment with meglitinides compared with those treated with the thiazolidinediones (TZDs) [IR = 9.94, 9.64, 15.71 and 20.32 per 1,000 patient-years for rosiglitazone, pioglitazone, nateglinide and repaglinide, respectively]. The plot of the hazard function and the estimated shape parameter from the Weibull regression model showed that pioglitazone, nateglinide and repaglinide had non-constant (decreasing) hazards over time, whereas

  12. Peripheral Biomarkers of Parkinson's Disease Progression and Pioglitazone Effects.

    Science.gov (United States)

    Simon, David K; Simuni, Tanya; Elm, Jordan; Clark-Matott, Joanne; Graebner, Allison K; Baker, Liana; Dunlop, Susan R; Emborg, Marina; Kamp, Cornelia; Morgan, John C; Ross, G Webster; Sharma, Saloni; Ravina, Bernard

    2015-01-01

    Pioglitazone, an oral hypoglycemic agent, recently failed to show promise as a disease-modifying agent in a 44-week phase 2 placebo-controlled study in 210 Parkinson's disease (PD) subjects. We analyzed peripheral biomarkers, including leukocyte PGC-1α and target gene expression, plasma interleukin 6 (IL-6) as a marker of inflammation, and urine 8-hydroxydeoxyguanosine (8OHdG) as a marker of oxidative DNA damage. Baseline or changes from baseline in biomarker levels were not associated with the rate of progression of PD. Pioglitazone did not significantly alter biomarker levels. Other agents that more effectively target these mechanisms remain of potential interest as disease modifying therapies in PD.

  13. 盐酸吡格列酮联合格列美脲治疗肥胖2型糖尿病患者的临床效果观察%Clinical effect of pioglitazone hydrochloride combined with glimepiride treating obese type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    王乐; 赵文婷

    2016-01-01

    pioglitazone combined with glimepiride group,with 18 cases in each group.The pioglitazone group had pioglitazone hydrochloride tablets 15-30 mg/time,1 time/d,orally administered before breakfast,the drug dosage could be adjusted depends on blood glucose values;the glimepiride group had glimepiride tablets 2 mg/time,1 time/d,orally administered 30 min before breakfast,the dosage could increase to 8 mg/d;the pioglitazone combined with glimepiride group orally took pioglitazone hydrochloride tablets 15-30 mg and glimepiride tablets 1 mg with a 0.5 h interval before breakfast,the glimepiride dosage was maintained and the pioglitazone dosage could be adjusted.After 12 weeks of treatment,fasting blood glucose,postprandial 2 h blood glucose,glycosylated hemoglobin and body mass index were analyzed and complications and adverse drug reactions were observed.Results Fasting blood glucose,postprandial 2 h blood glucose,glycosylated hemoglobin and body mass index in pioglitazone combined with glimepiride group were significantly lower than those in pioglitazone group andglimepiride group[(5.70 ± 0.31) mmol/L vs (9.00 ± 1.22),(10.50 ± 1.48) mmol/L;(7.00 ± 0.12) mmol/L vs (12.80 ± 0.44),(13.80 ± 0.12) mmol/L;(6.50 ± 0.03) % vs (11.00 ± 1.93) %,(10.03 ± 1.00) %;(19.50 ± 0.55) kg/m2 vs (24.30 ± 0.78),(22.00 ± 0.65) kg/m2] (all P < 0.05).There were no acute complications and adverse drug reactions in 3 groups.Conclusion Pioglitazone hydrochloride combined with glimepiride is more effective compared to single use of pioglitazone or glimepiride in the treatment of obese type 2 diabetes.

  14. Effects of mefformin and pioglitazone on bone metabolism in male patients with type 2 diabetes%二甲双胍和吡格列酮对男性2型糖尿病患者骨代谢指标的影响

    Institute of Scientific and Technical Information of China (English)

    王运林; 罗卓章

    2011-01-01

    目的 了解二甲双胍和毗格列酮对男性2型糖尿病患者骨代谢指标的影响.方法 将口服降糖治疗的90例男性2型糖尿病患者随机分为格列吡嗪组、格列吡嗪+二甲双胍组和格列吡嗪+吡格列酮组3组,治疗1年.治疗前后检测患者的空腹血糖(FBS)、空腹胰岛素(Ins)、糖化血红蛋白(HbAlc)、骨钙素、尿吡啶酚/尿肌酐(尿PYD/Cr).采用双能X线骨密度测量仪测量腰椎、髋部骨密度.结果 二甲双胍组腰椎骨密度平均增加0.49%,髋部骨密度平均增加1.82%.而吡格列酮组腰椎、髋部骨密度分别下降1.46%和1.97%左右.治疗后二甲双胍组髋部骨密度明显高于吡格列酮组.结论 与吡格列酮组比较,二甲双胍能明显增加男性糖尿病患者髋部骨密度.%Objective To compare changes in bone mineral density(BMD) and bone biochemical indicator during 1-year mefformin treatment with pioglitazone in type 2 diabetic men.Methods 90 men with type 2 diabetic were divided into three groups( glipizide group,glipizide + metformin group,glipizide + pioglitazone group).The metformin group were treated with glipizide and metformin.Pioglitazone group with pioglitazone and glipizide.BMD at the lumbar spine and hip was measure by dual-energy X-ray absorptiometry at the beginning and end of treatment.Samples were analyzed simultaneously for serum markers of bone formation osteocalcin(BGP) and markers of bone resorption urinary pyridinoline(uPYD) and urinary creatinine (Ct).Results In diabetic men.1-year Metformin treatment was associated with increased BMD at all sites studied.including 0.49% at the lumbar spine and 1.82% at the hip.whereas men in the pioglitazone group experienced a decrease in BMD about 1.46% at the lumbar spine and 1.97% at the hip.BMD in metformin group was higher than that in pioglitazone group at lumbar and hip.Conclusions Metformin increased BMD at hip in men with type 2 diabetes combared with pioglitazone.

  15. Formulation and development of self-microemulsifying drug delivery system of pioglitazone hydrochloride

    Directory of Open Access Journals (Sweden)

    Jyotsana R. Madan

    2014-01-01

    Full Text Available Self-microemulsifying drug delivery system (SMEDDS is a promising system for the Biopharmaceutics Classification System (BCS class II drugs. The current research aimed to improve the dissolution of poorly water-soluble antidiabetic drug pioglitazone HCl by formulating it in SMEDDS. Liquid SMEDDS of pioglitazone HCl were formulated with Capmul MCM C8 and oleic acid as oil phase, Cremophor RH 40 and Tween 80 as surfactant phase, and Transcutol P as cosurfactant phase after screening various vehicles. The prepared formulations were evaluated for self-emulsifying ability and phase diagram was constructed to optimize the system. These systems were further characterized for globule size, effect of pH and robustness, zeta potential, drug content, viscosity, self-emulsification time, polydispersity index, % transmittance, thermodynamic stability, surface morphology, and drug release. The system was robust to different pH media and dilution volumes. The optimized system possessed a mean globule size of 122.2 nm, zeta potential around -22.9 mV, drug content 99.66 ± 0.47%, viscosity 0.8874 ± 0.026 cP, emulsification time 38 s, polydispersity index value of 0.5, and transmittance value of 99.3 ± 0.6%. Drug release in hydrochloric acid buffer pH 2 was found to be 99.35 ± 0.38%. More than three-fold increase in dissolution characteristics of pioglitazone HCl in SMEDDS was observed as compared to pure and marketed formulation. Liquid SMEDDS filled in hard gelatin capsule (HGC shell was found to be compatible. Stability studies show there was no sign of phase separation or precipitation and no change in drug content was observed.

  16. Local release of pioglitazone (a peroxisome proliferator-activated receptor γ agonist) accelerates proliferation and remodeling phases of wound healing.

    Science.gov (United States)

    Sakai, Shigeki; Sato, Keisuke; Tabata, Yasuhiko; Kishi, Kazuo

    2016-01-01

    Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily known for its anti-inflammatory and macrophage differentiation effects, as well as its ability to promote fat cell differentiation and reduce insulin resistance. Pioglitazone (Pio) is a PPARγ agonist used clinically as an anti-diabetic agent for improving insulin sensitivity in patients with diabetes. The objective of this study was to develop a drug delivery system (DDS) for the local release of Pio to promote wound healing. Pio of low aqueous solubility was water-solubilized by micelles formed from gelatin grafted with L-lactic acid oligomers, and incorporated into a biodegradable gelatin hydrogel. An 8-mm punch biopsy tool was used to prepare two skin wounds on either side of the midline of 8-week-old mice. Wounds were treated by the hydrogels with (Pio-hydrogel group) or without (control group) Pio, and the wound area were observed 1, 4, 7, and 14 days after treatment. In addition, a protein assay and immunohistological stain were performed to determine the effects of the Pio-hydrogel on inflammation and macrophage differentiation. The Pio-hydrogels promote wound healing. Moreover, Western blotting analysis demonstrated that treatment with Pio-hydrogels resulted in decreased levels of the cytokines MIP-2 and TGF-β, and increased levels of glucose-regulating adiponectin. It is concluded that Pio-incorporated hydrogels promote the proliferation and remodeling phases of wound healing, and may prove to be effective as wound dressings.

  17. PPAR-γ2 and PTPRD gene polymorphisms influence type 2 diabetes patients' response to pioglitazone in China

    Institute of Scientific and Technical Information of China (English)

    Qi PEI; Zhao-qian LIU; Qiong HUANG; Guo-ping YANG; Ying-chun ZHAO; Ji-ye YIN; Min SONG; Yi ZHENG; Zhao-hui MO; Hong-hao ZHOU

    2013-01-01

    Aim: To investigate the influence of peroxisome proliferator-activated receptor y2 (PPAR-Y2) gene polymorphism rs1801282 and protein tyrosine phosphatase receptor type D (PTPRD) gene polymorphism rs17584499 on the occurrence of type 2 diabetes and pioglitazone efficacy in a Chinese Han population.Methods: One hundred ninety seven type 2 diabetes patients and 212 healthy controls were enrolled.Among them,67 type 2 diabetes patients were administered pioglitazone (30 mg/d,po) for 3 months.All the subjects were genotyped for genetic variants in PPAR-γ2 and PTPRD using MALDI-TOF mass spectrometry.Fasting plasma glucose,postprandial plasma glucose,glycated hemoglobin,serum triglyceride,total cholesterol,low-density and high-density lipoprotein-cholesterol were determined.Results: The PPAR-y2 gene rs1801282 polymorphism was significantly associated with type 2 diabetes susceptibility (OR=0.515,95% CI 0.268-0.990) and the PTPRD gene rs17584499 polymorphism was also significantly associated with type 2 diabetes (OR=1.984,95% Cl 1.135-3.469) in a dominant model adjusted for age,gender and BMI.After pioglitazone treatment for 3 months,the type 2 diabetes patients with PPAR-γ2 rs1801282 CG genotypes significantly showed higher differential values of postprandial plasma glucose and serum triglyceride compared with those with rs1801282 CC genotype.The patients with PTPRD rs17584499 CT+TT genotypes showed significantly lower differential value of postprandial plasma glucose compared to those with rs17584499 CC genotype.Conclusion: Diabetes risk alleles in PPAR-y2 (rs1801282) and PTPRD (rs17584499) are associated with pioglitazone therapeutic efficacy.

  18. Common polymorphisms of the peroxisome proliferator-activated receptor-gamma (Pro12Ala) and peroxisome proliferator-activated receptor-gamma coactivator-1 (Gly482Ser) and the response to pioglitazone in Chinese patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Hsieh, Ming-Chia; Lin, Kun-Der; Tien, Kai-Jen; Tu, Shih-Te; Hsiao, Jeng-Yueh; Chang, Shun-Jen; Lin, Shiu-Ru; Shing, Shih-Jang; Chen, Hung-Chun

    2010-08-01

    We investigated the effects of the common polymorphisms in the peroxisome proliferator-activated receptor-gamma (PPAR-gamma; Pro12Ala) and in PPAR-gamma coactivator-1(PGC-1; Gly482Ser) genes on the response to pioglitazone in Chinese with type 2 diabetes mellitus. A total of 250 patients with type 2 diabetes mellitus were treated with pioglitazone (30 mg/d) for 24 weeks without a change in previous medications. All patients were genotyped for the PPAR-gamma Pro12Ala and PGC-1 Gly482Ser polymorphisms. The Ala12Ala and Pro12Ala genotypes (26.0% vs 13.5%, P = .025) and Ala allele (15.6% vs 7.3%, P = .008) were significantly more frequent in pioglitazone responders than in nonresponders. The distribution of PGC-1 genotypes and alleles was not significantly different between responders and nonresponders. The decrease in fasting glucose (50.4 +/- 52.2 vs 43.3 +/- 51.7 mg/dL, P Pro12Ala and Ala12Ala) than in those without the allele (Pro12Pro). Baseline fasting glucose and triglyceride levels were related to the response of pioglitazone. Only the PPAR-gamma Pro12Ala polymorphism was found to be associated with the response of pioglitazone by multiple logistic regression analysis. The PPAR-gamma Pro12Ala gene polymorphism is associated with the response to pioglitazone in Chinese patients with type 2 diabetes mellitus. These findings may be helpful for targeted treatment of diabetes by identifying patients who are likely to respond to pioglitazone. Copyright 2010 Elsevier Inc. All rights reserved.

  19. Development and optimization of novel controlled-release pioglitazone provesicular powders using 3² factorial design.

    Science.gov (United States)

    Shukr, Marwa H; Eltablawy, Nadia A

    2015-02-01

    This work aimed at studying a novel controlled drug delivery proniosomal formulation of pioglitazone for treatment of diabetes type-2. The effects of independent variables like type of surfactant and ratio of surfactants/cholesterol were studied using 3(2) factorial design. The provesicular powders were characterized regarding their encapsulation efficiency, vesicle size, morphology, and in vitro drug release. The revealed optimal provesicular powder was exposed to stability testing and in vivo performance evaluation. Results showed that F6 was selected as the optimal formulation, and its in vivo hypoglycemic effect on normal healthy and STZ-induced diabetic albino rats was investigated. F6 proniosomal formulation exhibited a significantly higher % decrease (56.18 % for STZ-induced diabetic albino rats) of blood glucose level (BGL) than Actos® (32. % for STZ-induced diabetic albino rats). Higher % decrease of BGL with longer t max and lower AUC0-24 confirms the development of a successful proniosomal pioglitazone formulation.

  20. Potentiation of indomethacin-induced anti-inflammatory response by pioglitazone in carrageenan-induced acute inflammation in rats: Role of PPARγ receptors.

    Science.gov (United States)

    Houshmand, Gholamreza; Mansouri, Mohammad Taghi; Naghizadeh, Bahareh; Hemmati, Ali Asghar; Hashemitabar, Mahmoud

    2016-09-01

    This study aimed to assess the interaction between anti-inflammatory effects of pioglitazone (peroxysome proliferator activated receptor-gamma (PPARγ) agonist, PGL), and indomethacin (cyclooxygenase (COX) inhibitor, IND) and to evaluate the possible underlying mechanisms. Paw edema induced by carrageenan was used to induce inflammation. Different doses of IND (0.3-10mg/kg) and PGL (1-20mg/kg) alone or in combination were administered intraperitoneally to rats. Paw tissue levels of PPARγ, COX-2, and prostaglandin E2 and serum levels of TNF-α and IL-10 were also estimated. Doses of IND and PGL showed a statistically significant anti-inflammatory effect. Combination of a non-effective dose of IND (0.3mg/kg) with increasing doses of PGL (1-10mg/kg) resulted in potentiated anti-inflammation and vise versa. IND, PGL and the combination were able to reduce the COX-2, PGE2 contents and TNF-α level. Moreover, all these treatments caused elevation in PPARγ levels and IL-10 levels. However, when the rats were pre-treated with GW-9662 (a selective PPARγ antagonist), all the anti-inflammation and alterations in the biochemical factors were antagonized. These results showed that PGL markedly enhanced the anti-inflammatory activity of IND and this effect mediated partly at least, through PPARγ. Possible mechanisms of the interaction were that PGL stimulates the PPARγ and inhibits COX-2 by those cytokines that trigger the PPARγ and also inhibit COX-2. This study suggests that combination therapy with pioglitazone and indomethacin may provide an alternative for the clinical control of inflammation especially in patients with diabetes.

  1. DEVELOPMENT AND EVALUATION OF MICROBALLOONS OF PIOGLITAZONE HYDROCHLORIDE USING EUDRAGIT S-100

    Directory of Open Access Journals (Sweden)

    Nishant S. Gandhi et al.

    2012-01-01

    Full Text Available ABSTRACTKeywords:Pioglitazone hydrochloride,Eudragit S-100,Solvent diffusion evaporation,Floating microspheres,Polymer: Drug ratioCorrespondence to Author:Nishant GandhiOld Power House Road, Ramnagar, Gondia, Maharashtra, IndiaVarious approaches have been used to retain the dosage form in the stomach as a way of increasing the gastric residence time (GRT, including floatation systems; high-density systems; mucoadhesive systems; magnetic systems; unfoldable, extendible, or swellable systems; and superporous hydrogel systems. The aim of this study was to prepare and evaluate floating microspheres of Pioglitazone hydrochloride for the prolongation of gastric residence time. The microspheres were prepared by emulsion solvent diffusion-evaporation method using Eudragit S-100. A full factorial design was applied to optimize the formulation. Preliminary studies revealed that the concentration of polymer and stirring speed significantly affected the characteristics of floating microspheres. The optimum batch of microspheres exhibited some rough surfaces with good flow and packing properties, prolonged sustained drug release, remained buoyant for more than 10 hrs, high entrapment efficiency upto 89%w/w. Scanning electron microscopy confirmed the hollow structure with particle size in the order of 270 µm. The studies revealed that decrease in particle size of the microspheres increase the drug release from the floating microspheres. The results of 32 full factorial design revealed that the Polymer: Drug (P: D ratio (X1 and stirring speed (X2 significantly affected drug entrapment efficiency, percentage release after 8 h and particle size of microspheres.

  2. 吡格列酮对早期糖尿病肾病大鼠血清一氧化氮和一氧化氮合酶的影响%Pioglitazone reduces serum nitric oxide and nitricoxide synthase in rats with early diabetic nephropathy

    Institute of Scientific and Technical Information of China (English)

    杨前勇; 聂忠; 宋宁燕

    2011-01-01

    pioglitazone at 10 mg/( kg · D). The serum NO concentration and activities of T-NOS, iNOS, cNOS were measured at the end of the tenth week. Results There were no significant differences in the NO level and T-NOS and iNOS activities between the NCT and NC groups ( P > 0. 05 ). The increased NO level and T-NOS and iNOS activities in diabetic rats were significantly attenuated by pioglitazone treatment ( P 0.05). Conclusion The serum NO level and iNOS activity are markedlyelevated in early DN rats. Pioglitazone protects the kidney by lowering the NO level and iNOS activity.

  3. Total and high molecular weight (HMW) adiponectin levels and measures of glucose and lipid metabolism following pioglitazone treatment in a randomized placebo-controlled study in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Frystyk, Jan; Højlund, Kurt;

    2008-01-01

    .89) and Delta-oxidative glucose metabolism (r = 0.71) and inversely with Delta-fasting free fatty acid (FFA) levels (r = -0.69) and Delta-lipid oxidation (r = -0.73) during insulin stimulation (all P ... and lipid metabolism during insulin stimulation than with Delta-total adiponectin. CONCLUSION: A close correlation between increased total adiponectin levels and increased insulin-stimulated glucose metabolism during pioglitzone treatment supports the hypothesis that the insulin-sensitizing effect......OBJECTIVE: Recent studies suggested that the effect of adiponectin on insulin-stimulated glucose metabolism is mediated primarily by the high molecular weight (HMW) form of adiponectin. In the present study we evaluated total and HMW adiponectin in polycystic ovary syndrome (PCOS) patients...

  4. Lobeglitazone and pioglitazone as add-ons to metformin for patients with type 2 diabetes: a 24-week, multicentre, randomized, double-blind, parallel-group, active-controlled, phase III clinical trial with a 28-week extension.

    Science.gov (United States)

    Jin, S-M; Park, C-Y; Cho, Y M; Ku, B J; Ahn, C W; Cha, B-S; Min, K W; Sung, Y A; Baik, S H; Lee, K W; Yoon, K-H; Lee, M-K; Park, S W

    2015-06-01

    We aimed to compare the efficacy and safety of lobeglitazone and pioglitazone as add-ons to metformin in patients with type 2 diabetes. Patients who were inadequately controlled by metformin were randomized and treated once daily with either lobeglitazone (0.5 mg, n = 128) or pioglitazone (15 mg, n = 125) for 24 weeks, with a 28-week extension trial of lobeglitazone treatment in patients who consented. The primary endpoint was the change in glycated haemoglobin (HbA1c) concentration from baseline to week 24. At week 24, the mean change from baseline in HbA1c was -0.74% for the lobeglitazone group and -0.74% for the pioglitazone group, with a mean difference of 0.01% [95% confidence interval (CI) of difference, -0.16 to 0.18]. The effects of lobeglitazone on lipid variables and the adverse events associated with lobeglitazone were similar to those observed with pioglitazone. Lobeglitazone was not inferior to pioglitazone as an add-on to metformin in terms of their efficacy and safety.

  5. Linagliptin and pioglitazone combination therapy versus monotherapy with linagliptin or pioglitazone: A randomised, double-blind, parallel-group, multinational clinical trial.

    Science.gov (United States)

    Nauck, Michael Albrecht; di Domenico, Maximiliano; Patel, Sanjay; Kobe, Maureen; Toorawa, Robert; Woerle, Hans-Juergen

    2016-07-01

    Linagliptin plus pioglitazone single-pill combinations were evaluated. Patients (n = 936) with insufficient glycaemic control, despite lifestyle interventions, were randomised for 30 weeks to either monotherapy with linagliptin 5 mg; pioglitazone 15, 30 or 45 mg; or single-pill combination with linagliptin 5 mg plus pioglitazone 15, 30 or 45 mg. An extension (⩽54 weeks) planned to evaluate linagliptin plus pioglitazone 30 or 45 mg single-pill combinations was not completed due to a protocol amendment. Adjusted mean (95% confidence interval) differences in HbA1c change from baseline at week 30 for linagliptin plus pioglitazone 15, 30 and 45 mg were -0.17% (-0.41, 0.07), -0.37% (-0.60, -0.14) and -0.41% (-0.64, -0.18) versus pioglitazone monotherapies, respectively, and -0.44% (-0.67, -0.20), -0.68% (-0.91, -0.44) and -0.89% (-1.12, -0.66) versus linagliptin monotherapy, respectively. Single-pill combinations were generally well tolerated. Hypoglycaemia frequency was ⩽1.5% per group. Linagliptin plus pioglitazone combinations were efficacious, with safety profiles comparable to the individual monotherapies.

  6. Increasing trend of metronidazole resistance in the treatment of ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-02-22

    Feb 22, 2010 ... Antibiotic resistance is an ever increasing problem with the treatment of ... pylori treatment posses serious public health problems and is therefore necessary that new drug ..... to add to existing global knowledge the types of.

  7. Pioglitazone improves insulin sensitivity, reduces visceral fat and stimulates lipolysis in non diabetic dialyzed patients

    Directory of Open Access Journals (Sweden)

    Anne Zanchi

    2012-06-01

    Full Text Available Insulin resistance is common in dialyzed patients and is associated with increased mortality and protein-energy wasting. The aim of this study was to investigate the effect of pioglitazone (PIO, a powerful insulin sensitizer, on insulin sensitivity, body composition and adipose tissue metabolism, in dialyzed patients. A double blind randomized cross-over study was performed in non diabetic dialysis patients. Each patient followed 2 treatment phases of 16 weeks, starting either with oral PIO 45 mg/d or placebo (PL, and then switched to the other phase. At the end of each phase, patients underwent hyperinsulinemic euglycemic clamps, dual energy X-ray absorptiometry, an abdominal CT, and extensive plasma biochemical analysis. Twelve patients including 8 HD (59.6±4.4 y and 4 PD patients (43.5±3.6 y were recruited. Nine patients completed both phases and 3 patients dropped out (renal transplantation/2 HD and peritonitis/1 PD. PIO was safe and well tolerated. Under PIO, insulin sensitivity improved, as assessed by increased total glucose disposal rate (1.98±0.24 for PIO versus 1.58±0.12 umol/kg/min for PL, p<0.05, and reduced glucose endogenous hepatic production. PIO did not affect post-dialysis body weight, total fat and lean body mass, but significantly reduced visceral adipose tissue (VAT area and the VAT/SAT (subcutaneous adipose tissue ratio. HDL-cholesterol significantly increased. PIO decreased CRP (3.96±1.44 mg/l vs 7.88±2.56, p<0.05, plasma leptin, and dramatically reduced leptin/adiponectin ratio. Glycerol turnover, circulating glycerol and non esterified fatty acids were paradoxically increased. In conclusion, the improvement in insulin sensitivity by PIO, in non diabetic dialyzed patients, was associated with favorable metabolic effects, reduction in inflammation and body fat redistribution. The stimulation of systemic lipolysis was a surprising finding which may reflect adipose tissue remodeling and/or a paradoxical lypolitic

  8. Effect of pioglitazone combined with cyproterone acetate on the reproductive hormone level and insulin resistance of patients with polycystic ovary syndrome

    Institute of Scientific and Technical Information of China (English)

    Hong-Wei Hao; Dong-Zhen Liu

    2015-01-01

    Objective: To analyze the effect of Pioglitazone combined with cyproterone acetate on the reproductive hormone level and insulin resistance of patients with polycystic ovary syndrome. Methods: 96 patients with the polycystic ovary syndrome in our hospital were randomly divided into observation group and controlgroup two groups, each of 48 cases. The control group was treated with the treatment of cyproterone acetate, observation group was treated with pioglitazone combined with cyproterone acetate treatment. The clinical efficacy of two groups were compared. The serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T) and fasting plasma glucose (FBG), fasting insulin (FINS) level before and after treatment and calculate the insulin resistance index (IR) were observed. Results: After treatment, serum FSH, LH and T levels of two groups were significantly lower than that before treatment (P0.05). FBG, FINS and IR of the patients in the observation group were significantly lower than the control group (P<0.05). Conclusion: pioglitazone combined with cyproterone acetate has significant therapeutic effect on polycystic ovary syndrome, can effectively improve the patients with insulin resistance and reproductive hormone disorder.

  9. Effect of pioglitazone on the growth of normal bladder transitional epithelial cells and bladder cancer cells%吡格列酮对膀胱正常移行上皮细胞及膀胱癌细胞生长的影响

    Institute of Scientific and Technical Information of China (English)

    王吉娇; 李春艳; 袁晓岚; 周姣姣; 严静; 初蕊; 杨丰强; 曲伸; 苏本利

    2014-01-01

    以不同浓度吡格列酮处理膀胱正常移行上皮细胞及膀胱癌J82细胞24 h 、48 h 、72 h、5 d、8 d和10d,观察细胞生长状态,MTT检测细胞生长抑制率,流式细胞仪分析细胞凋亡,实时定量PCR和Western印迹法检测周期素D1 、p53、Bcl-2、Bax的mRNA和蛋白表达.结果显示,10 μmol/L吡格列酮处理膀胱正常细胞24、48、72 h后细胞生长明显受抑制(均P<0.05),细胞凋亡增加[24 h(18.8 ±2.1对9.4±1.7)% 、48 h(29.9±1.3对10.7±1.1)、72 h(49.7±2.3对11.3±1.3)%,P<0.05],J82细胞未见明显影响 . 10 μmol/L吡格列酮处理2种细胞72 h内周期素D1 、p53、Bcl-2、Bax的mRNA和蛋白表达均无明显变化,作用8d后J82细胞周期素D1 、p53蛋白表达降低,提示吡格列酮不增加膀胱正常移行上皮细胞癌变趋势.%The normal bladder transitional cells and bladder cancer J82 cells were treated with various concentrations of pioglitazone for 24 h,48 h,72 h,8 d,and 10 d.The growth of the cells was tested by MTT.Apoptosis rate was detected by flow cytometry technology.Realtime-PCR and Western blot were used to analyze the mRNA and protein expressions of p53,cvclin D1,Bcl-2,and Bax.lhe results showed that the cell viability of normal bladder cells was decreased 24,48,and 72 h after 10 μmol/L pioglitazone treatment (all P<0.05) while the cell apoptosiswasincreased [24h(18.8±2.1 vs 9.4 ± 1.7) %,48 h (29.9 ± 1.3 vs 1 0.7 ± 1.1),72 h (49.7 ±2.3 vs11.3 ± 1.3) %,P<0.05].Pioglitazone had no effect on the growth and proliferation of J82 cells.There were no significant differences in mRNA and protein expressions of p53,cvclin D1,Bcl-2,and Bax within 72 h after pioglitazone treatment in this two kinds of cells.But,the protein expressions of cvclin D1 and p53 in J82 cells were decreased after pioglitazone treatment for 8 days.These results suggest that pioglitazone does not increase the risk of bladder cancer in normal transitional cells.

  10. 吡格列酮对非酒精性脂肪性肝病患者的氧化应激参数和炎症因子的影响%Effects of pioglitazone on oxidative stress-related parameters and inflammatory cytokines in patients with nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    方文军; 陆帅; 王娟; 胡静芳; 苏青

    2013-01-01

    Objective To investigate the effect of pioglitazone on oxidative stress-related parameters and inflammatory cytokines in patients with nonalcoholic fatty liver disease (NAFLD).Methods In this randomized,singleblind,controlled study,106 patients with NAFLD without diabetes were randomized into two groups.Fifty-two patients in the pioglitazone group received pioglitazone 30 mg/d with a course of 24 weeks,while the other 54 patients were served as controls.The levels of serum alanine aminotransferase (ALT),gamma-glutamyl transferase (GGT),free fatty acids (FFA),malondialdehyde (MDA),4-hydroxy-2-nonenal (4-HNE),interleukin (IL)-1β,IL-6,tumor necrosis factor-α (TNF-α),CT value ratio of liver and spleen,and homeostatic model assessment for insulin resistance (HOMA-IR) were measured before and after treatment.Results There were no significantly differences in baseline characteristics between two groups (P> 0.05).After 24 weeks treatment,CT value ratio of liver and spleen increased (P<0.05),and the levels of serum ALT,GGT,FFA,MDA,4-HNE,IL-1β,IL-6,TNF-α and HOMA-IR decreased in pioglitazone group (all P<0.05),and no obvious changes was observed in control group.No serious adverse reaction was observed in pioglitazone group.Conclusions Pioglitazone may decrease hepatic fat content and levels of oxidative stress-related parameters and inflammatory cytokines in patients with NAFLD.%目的:观察吡格列酮对非糖尿病非酒精性脂肪性肝病(NAFLD)患者肝脏脂肪含量及氧化应激参数和炎症因子水平的影响,探讨吡格列酮防治NAFLD的可能作用机制.方法:采用随机、单盲、对照组的研究.106例非糖尿病NAFLD患者随机分为吡格列酮组52例和对照组54例,对照组予以常规生活方式干预,吡格列酮组在常规生活方式干预的基础上予吡格列酮30 mg,1次/d,疗程均为24周.检测2组患者干预前后的肝/脾CT比值、血清丙氨酸转氨酶(ALT)、y-谷氨酰转肽酶(GGT)、游离

  11. Efficacy and safety of pioglitazone added to alogliptin in Japanese patients with type 2 diabetes mellitus: a multicentre, randomized, double-blind, parallel-group, comparative study.

    Science.gov (United States)

    Kaku, K; Katou, M; Igeta, M; Ohira, T; Sano, H

    2015-12-01

    A phase IV, multicentre, randomized, double-blind, parallel-group, comparative study was conducted in Japanese subjects with type 2 diabetes mellitus (T2DM) who had inadequate glycaemic control, despite treatment with alogliptin in addition to diet and/or exercise therapy. Subjects with glycated haemoglobin (HbA1c) concentrations of 6.9-10.5% were randomized to receive 16 weeks' double-blind treatment with pioglitazone 15 mg, 30 mg once daily or placebo added to alogliptin 25 mg once daily. The primary endpoint was the change in HbA1c from baseline at the end of treatment period (week 16). Both pioglitazone 15 and 30 mg combination therapy resulted in a significantly greater reduction in HbA1c than alogliptin monotherapy [-0.80 and -0.90% vs 0.00% (the least squares mean using analysis of covariance model); p Pioglitazone/alogliptin combination therapy was effective and generally well tolerated in Japanese subjects with T2DM and is considered to be useful in clinical settings.

  12. Effect of Pioglitazone on Renal Osteopontin Expression in Diabetic Rats%吡格列酮对糖尿病大鼠肾脏骨桥蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    张世静; 王建平

    2013-01-01

    were observed under light microscope. The expressions of OPN protein and OPN mRNA were detected by immunohisto-chemistry and reverse transcription-polymerase chain reaction ( RT-PCR) , respectively. RESULTS Treatment with 3 and 15 mg · kg-1 · d-1 pioglitazone could decrease Scr, mAlb and RKW in diabetic rats. Compared with diabetic rats, blood glucose level was lower in diabetic rats treated with 15 mg · kg ·d-1 pioglitazone; however, no significant change was observed at the 3 mg·kg-1· d-1 dose. Compared with normal control rats, the OPN protein and mRNA expressions of the whole nephritic kidney in diabetic rats were upregulated (P <0. 05). After treatment with 3 and 15 mg·kg-1 · d-1 pioglitazone, the expressions of OPN protein and mRNA reduced compared with diabetic rats ( P < 0. 05 ). CONCLUSION The OPN expression in renal tissues is increased in diabetic rats, suggesting that OPN has emerged as a potential key pathophysiologic contributor in diabetic nephropathy ( DN). Pioglitazone can reduce microalbuminuria in diabetic rats. The renal protective effect of pioglitazone in DN may involve the suppression of increased OPN.

  13. A randomized placebo-controlled study on the effects of pioglitazone on cortisol metabolism in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Hermann, Anne Pernille; Hagen, Claus

    2009-01-01

    OBJECTIVE: To investigate possible effects of insulin-sensitizing treatment on cortisol metabolism in insulin-resistant patients with polycystic ovary syndrome (PCOS). DESIGN: Randomized placebo-controlled study. SETTING: Academic tertiary care medical center. PATIENT(S): Thirty insulin-resistant......OBJECTIVE: To investigate possible effects of insulin-sensitizing treatment on cortisol metabolism in insulin-resistant patients with polycystic ovary syndrome (PCOS). DESIGN: Randomized placebo-controlled study. SETTING: Academic tertiary care medical center. PATIENT(S): Thirty insulin......-resistant PCOS patients. INTERVENTION(S): Sixteen weeks of pioglitazone (30 mg/day) or placebo treatment. MAIN OUTCOME MEASURE(S): Twenty-four-hour 20 min integrated blood sampling for measurement of cortisol and 24 h urinary excretion of steroid metabolites. Relative 5alpha-reductase activity was evaluated...... levels. Delta A/E ratio inversely correlated with Delta IGF-I and Delta peak GH during GH stimulation tests. No significant changes were measured in T, DHT, DHEA, DHEAS, 24 h mean cortisol, or urinary excretion of steroid metabolites. CONCLUSION(S): Pioglitazone decreased relative 5alpha...

  14. A COMPARATIVE STUDY OF ROSIGLITAZONE AND PIOGLITAZONE TO EVALUATE THE CARDIOVASCULAR EFFECTS IN HIGH FRUCTOSE DIET INDUCED HYPERTENSIVE RATS

    Directory of Open Access Journals (Sweden)

    Arghya Biswas et al

    2012-09-01

    Full Text Available Thiazolidinediones (TZDs were widely used for the treatment of type 2 diabetes. Recent studies have shown that TZDs have paradoxical effects on cardiovascular diseases. The objective of the present study was to investigate the effect of TZDs (Rosiglitazone and Pioglitazone in High Fructose Diet (HFD induced hypertension in rats. HFD was given for 14 weeks. After 8 weeks of hypertension induction period, treatment phase was started with Rosiglitazone (ROSI 10 and 30 mg/kg, p.o. and Pioglitazone (PIO 10 and 30 mg/kg, p.o. to the respective groups which were continued till 6 weeks. Systolic Blood Pressure (SBP was measured weekly and serum glucose, triglyceride, cholesterol and HDL-C were measured at the end of study period. In HFD fed rats hypertension was observed after 8 weeks. Treatment with the test drugs significantly reversed the changes in serum enzyme levels as well as SBP made by HFD feeding compared to the control group. The study concludes that TZDs possess antihypertensive effect as exhibited in the present experimental settings.

  15. Pioglitazone attenuates tactile allodynia and thermal hyperalgesia in mice subjected to peripheral nerve injury.

    Science.gov (United States)

    Maeda, Takehiko; Kiguchi, Norikazu; Kobayashi, Yuka; Ozaki, Masanobu; Kishioka, Shiroh

    2008-11-01

    To clarify the role of peroxisome proliferator activated receptor gamma (PPARgamma) in neuropathic pain, we examined the effect of pioglitazone, a PPARgamma agonist, on tactile allodynia and thermal hyperalgesia in a neuropathic pain model. Mice were subjected to partial sciatic nerve ligation (PSL) and given pioglitazone (1 - 25 mg/kg, p.o.) once daily. PPARgamma was distributed in the neurons of the dorsal root ganglion and the dorsal horn of the spinal cord and in the adipocytes at the epineurium of the sciatic nerve in naive mice. PSL elicited tactile allodynia and thermal hyperalgesia for two weeks. Administration of pioglitazone for the first week after PSL attenuated thermal hyperalgesia and tactile allodynia, which was dose-dependent and blocked by GW9662 (2 mg/kg, i.p.), a PPARgamma antagonist. Administration of pioglitazone for the second week also relieved tactile allodynia, but administration one week before PSL had no effect. A single administration of pioglitazone to mice on day 7 of PSL did not alter tactile allodynia and thermal hyperalgesia. PSL-induced upregulation of tumor necrosis factor-alpha and interleukin-6, which are essential for neuropathic pain, was suppressed by pioglitazone for the first week. This suggests that pioglitazone alleviates neuropathic pain through attenuation of proinflammatory cytokine upregulation by PPARgamma stimulation.

  16. The effect of pioglitazone on the high protein diet of diabetic nephropathy rats%吡格列酮干预对高蛋白饮食糖尿病大鼠肾病的影响

    Institute of Scientific and Technical Information of China (English)

    张俊峰

    2016-01-01

    Objective:To investigate the effect of pioglitazone on the high protein diet of diabetic nephropathy(DN) rats. Methods:Diabetes mellitus( DM)rats were randomly divided into 3 groups,15 rats in each group:DM group, 7. 5mg/ kg pioglitazone group and 15. 0mg/ kg pioglitazone group,15 healthy rats were collected as the control group. The control group was fed with normal diet. And the DM rats were administered high protein diet. All groups were treated for 8 weeks. Fasting blood glucose(FBG),urine albumin(UA)and urinary creatinine(UC)were collected on the beginning, 4th week and 8th week of treatment. On the 8th week,triglyceride(TG),total cholesterol(TC),serum creatinine(SCr), blood urea nitrogen(BUN),malondialdehyde(MDA),catalase(CAT)in blood were defined and ICAM-1,glomerular monocyte / macrophage infiltration and glomerular basement membrane(GBM)in kidney were defined. Results:No rat died during the experiment. FBG,UA,UC at the beginning,4th week and 8th week of treatment in DM group were higher,and TC,TG,BUN,Scr,kidney index,ICAM - 1,glomerular monocyte / macrophage infiltration,MDA and GMB were higher in DM group on the 8th week of treatment. Compared with DM group,FBG,UA,UC at the beginning,4th week and 8th week of treatment were decreased,and TC,TG,BUN,Scr,kidney index,ICAM-1,glomerular monocyte / macrophage infiltration,MDA and GMB were decreased in pioglitazone groups( P < 0. 05). Compared with 7. 5mg/ kg pioglitazone group,FBG,UA,UC at the beginning,4th week and 8th week of treatment were decreased,and TC,TG,BUN,Scr,kid-ney index,ICAM-1,glomerular monocyte / macrophage infiltration and MDA were decreased in 15. 0 mg/ kg pioglitazone group. Compared with the control group,CAT was decreased in the DM group(P < 0. 05). Compared with the DM group, CAT was increased in the pioglitazone groups,and higher in 15. 0 mg/ kg pioglitazone group(P < 0. 05). Conclusion Piogl-itazone can protect the renal function of DN by decreasing the expression of CAM-1,glomerular

  17. The efficacy of methotrexate plus pioglitazone vs. methotrexate alone in the management of patients with plaque-type psoriasis: a single-blinded randomized controlled trial.

    Science.gov (United States)

    Lajevardi, Vahide; Hallaji, Zahra; Daklan, Soroush; Abedini, Robabeh; Goodarzi, Azadeh; Abdolreza, Mona

    2015-01-01

    Recently, thiazolidinediones have shown to be efficacious with a favorable safety profile when used in the treatment of chronic plaque-type psoriasis. The aim of this study was to evaluate and compare the efficacy and safety of a combination of methotrexate plus pioglitazone and methotrexate alone in plaque-type psoriasis. A total of 44 adult patients with plaque-type psoriasis were included in the study. Patients were randomized to treatment with methotrexate alone (group A) or methotrexate plus pioglitazone (group B) for 16 weeks. The primary efficacy outcome measure was psoriasis area and severity index (PASI) score change between the study groups at week 16 relative to baseline. The secondary efficacy outcome measure was dermatology life quality index (DLQI) score change between the two groups at week 16 relative to baseline. The PASI 75 score was also measured. After 16 weeks of therapy, the percentage of reduction in the mean PASI score was 70.3% in group B and 60.2% in group A. PASI 75 was achieved in 14 patients (63.6%) in group B compared with two patients (9.1%) in group A within 16 weeks, which was significant (P methotrexate in plaque-type psoriasis, as demonstrated by a reduction in the mean PASI scores. In terms of DLQI, there was no extra benefit by the addition of pioglitazone to methotrexate therapy.

  18. Endoplasmic reticulum stress-related protective effect of pioglitazone on the myocardium with ischemia-reperfusion injury%吡格列酮对大鼠缺血再灌注诱导的内质网应激相关的心肌保护作用

    Institute of Scientific and Technical Information of China (English)

    李艳; 陈还珍; 范学秀; 王妍妍

    2013-01-01

    Objective To observe influence of pioglitazone on the expression of JNK/p-JNK and cas-pase-12 in ischemia-reperfusion in rats, and discuss the myocardial protective effect of pioglitazone to the endo-plasnnc reticulurn stress way through the JNK pathway. Methods Forty rats were randomly divided into lour groups: sham operation group (n-10). ischemia-reperfusion group (n=10). pioglitazone 10 mg treated group (n= 10), pioglitazone 10 mg treated and SP600125 group (n= 10). Left anterior descending coronary artery was ligated for 30 mm and reperfused for 2 hour to establish the model of ischemia-reperfusion. TUNEL was performed to detect apoplosis of myocardial cells, immunohistochemislry was performed to detect the expression of caspase -12, Western blot was performed to detect the expression of JNK and p-JNK, Results The apoptosis index and the expression of caspase-12 and the expression of p-JNK in ischemia-reperfusion group increased after ischemia-reper - fusion compared with sham operation group and pioglitazone treatment reduced the above index, SP600125 augmented the reducing effect. Conclusion Ischemia-reperfusion can activate INK access and induce severe ER then aggravate cell apoptosis induced by ERS. Pioglitazone could reduce the myocardial apoptosis induced by ERS, which are important protection factors are mediated by JNK.%目的 观察吡格列酮对大鼠心肌缺血再灌注损伤(MIRI)时JNK、p-JNK及caspase-12蛋白表达的影响,探讨吡格列酮通过JNK通路对内质网应激途径的心肌保护作用.方法 Wistar大鼠40只随机分为假手术组(sham组)、缺血再灌注组(I/R组)、I/R+Pio(吡格列酮)组及I/R+Pio+SP600125组各10只.制作大鼠MIRI模型;TUNEL检测心肌细胞凋亡,免疫组织化学检测各组caspase-12表达变化,western Blot法检测各组JNK、p-JNK的表达.结果 吡格列酮预处理组大鼠心肌细胞凋亡、JNK磷酸化率及caspase-12蛋白表达水平明显比I/R组降低(P<0.05),

  19. Increases in pediatric antiretroviral treatment, South Africa 2005-2010.

    Directory of Open Access Journals (Sweden)

    Sandeep D Patel

    Full Text Available BACKGROUND: In South Africa in 2010, about 340,000 children under the age of 15 were infected with HIV. We describe the increase in the treatment of South African pediatric HIV-infected patients assisted by the President's Emergency Plan for AIDS Relief (PEPFAR from 2004 to 2010. METHODS: We reviewed routine program data from PEPFAR-funded implementing partners among persons receiving antiretroviral treatment age 15 years old and less. Data quality was assessed during the reporting period by program officials through routine analysis of trends and logic checks. Based on UNAIDS estimated mortality rates of untreated HIV-infected children, we calculated the number of deaths averted and life-years gained in children under five receiving PEPFAR-assisted antiretroviral treatment. RESULTS: From October 2004 through September 2010, the number of children newly initiated on antiretroviral treatment in PEPFAR-assisted programs increased from 154 to 2,641 per month resulting in an increase from 2,412 children on antiretroviral treatment in September 2005 to 79,416 children in September 2010. Of those children who initiated antiretroviral treatment before September 2009, 0-4 year olds were 1.4 (95% CI: 1.3-1.5 times as likely to transfer out of the program or die as 5-14 year olds; males were 1.3 (95% CI: 1.0-1.7 times as likely to stop treatment as females. Approximately 27,548 years of life were added to children under-five years old from PEPFAR-assisted antiretroviral treatment. CONCLUSIONS: Pediatric antiretroviral treatment in South Africa has increased substantially. However, additional case-finding and a further acceleration in the implementation of pediatric care and treatment services is required to meet the current treatment need.

  20. Effects of the PPARγ agonist pioglitazone on coronary atherosclerotic plaque composition and plaque progression in non-diabetic patients: a double-center, randomized controlled VH-IVUS pilot-trial.

    Science.gov (United States)

    Christoph, Marian; Herold, Joerg; Berg-Holldack, Anna; Rauwolf, Thomas; Ziemssen, Tjalf; Schmeisser, Alexander; Weinert, Sönke; Ebner, Bernd; Said, Samir; Strasser, Ruth H; Braun-Dullaeus, Ruediger C

    2015-05-01

    Despite the advanced therapy with statins, antithrombotics and antihypertensive agents, the medical treatment of coronary artery disease is less than optimal. Therefore, additional therapeutic anti-atherosclerotic options are desirable. This VH-IVUS study (intravascular ultrasonography with virtual histology) was performed to assess the potential anti-atherogenic effect of the PPARγ agonist pioglitazone in non-diabetic patients. A total of 86 non-culprit atherosclerotic lesions in 54 patients with acute coronary syndrome were observed in a 9-month prospective, double-blind, and placebo-controlled IVUS study. Patients were randomized to receive either 30 mg pioglitazone (Pio) or placebo (Plac). As primary efficacy parameter, the change of relative plaque content of necrotic core was determined by serial VH-IVUS analyses. Main secondary endpoint was the change of total plaque volume. In contrast to placebo, in the pioglitazone-treated group, the relative plaque content of necrotic core decreased significantly (Pio -1.3 ± 6.9% vs. Plac +2.6 ± 6.5%, p < 0.01). In comparison to the placebo group, the plaques in pioglitazone-treated patients showed significantly greater reduction of the total plaque volume (Pio -16.1 ± 26.4 mm3 vs. Plac -1.8 ± 30.9 mm3, p = 0.02). Treatment with a PPARγ agonist in non-diabetic patients results in a coronary artery plaque stabilization on top of usual medical care.

  1. Risperidone treatment increases CB1 receptor binding in rat brain

    DEFF Research Database (Denmark)

    Secher, Anna; Husum, Henriette; Holst, Birgitte

    2010-01-01

    BACKGROUND/AIMS: Body weight gain is a common side effect of treatment with antipsychotics, but the mechanisms underlying this weight gain are unknown. Several factors may be involved in antipsychotic-induced body weight gain including the cannabinoid receptor 1 (CB(1)), the serotonin receptor 2C...... positively correlated with visceral fat mass. Risperidone treatment increased CB(1) receptor binding in the arcuate nucleus (40%), hippocampus (25-30%) and amygdala (35%) without concurrent alterations in the CB(1) receptor mRNA. Risperidone treatment increased adiponectin mRNA. CONCLUSION: The present study...... showed that risperidone treatment altered CB(1) receptor binding in the rat brain. Risperidone-induced adiposity and metabolic dysfunction in the clinic may be explained by increased CB(1) receptor density in brain regions involved in appetite and regulation of metabolic function....

  2. The role of peroxisome proliferator-activated receptor and effects of its agonist, pioglitazone, on a rat model of optic nerve crush: PPARγ in retinal neuroprotection.

    Directory of Open Access Journals (Sweden)

    Juming Zhu

    Full Text Available It has been shown that peroxisome proliferators-activated receptor gamma (PPARγ is beneficial for central nervous system injury. However its role on optic nerve injury remains unknown. In the present study, we examined the change of PPARγ expression in rat retina following optic nerve injury and investigated the effect of pioglitazone (Pio, a PPARγ agonist, on retinal ganglion cells (RGCs neuroprotection using a rat optic nerve crush (ONC model. Our results showed that PPARγ mRNA and protein levels were increased after ONC, and most of PPARγ-immunoreactive cells colocalized with Müller cells. Pio treatment significantly enhanced the number of surviving RGCs and inhibited RGCs apoptosis induced by ONC. However, when PPARγ antagonist GW9662 was used, these neuroprotective effects were abolished. In addition, pio attenuated Müller cell activation after ONC. These results indicate that PPARγ appears to protect RGCs from ONC possibly via the reduction of Müller glial activation. It provides evidence that activation of PPARγ may be a potential alternative treatment for RGCs neuroprotection.

  3. Optimal treatment increased the seed germination of Salvia verticillata L.

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    ALALEH KHAKPOOR

    2015-12-01

    Full Text Available Most seeds of the medicinal species are variable regarding their ecological compatibility with environmental conditions. Therefore, identifying the ecophysiological factors that affect dormancy and create optimal conditions for seed germination of medicinal plants is necessary for their culture and production. To evaluate the effect of different treatments on seed germination of medicinal species of Salvia verticillata, collected in the summer of 2010 in Eastern Azarbaijan, we have performed completely randomized experimental tests with 4 replications. The experimental design of treatment prior to growth included: scrape the skin with sandpaper, treatment with 500 ppm gibberellic acid for 24 and 48 h, treatment with citric acid for 10, 20 and 30 minutes, chilling for 2 and 4 weeks, treatment with warm water at 70°C and control treatment. Results showed that the effect of different treatments was significant on seed germination percent of the medicinal plant Salvia verticillata. Scrape the skin with sandpaper, citric acid treatment for 10, 20 and 30 minutes, and gibberellic acid treatment for 24 hours, increased the germination percentage compared to the control treatment. The most positive impact was observed on the dormancy breaking and germination of medicinal species Salvia verticillata.

  4. Maternal Baicalin Treatment Increases Fetal Lung Surfactant Phospholipids in Rats

    Directory of Open Access Journals (Sweden)

    Chung-Ming Chen

    2011-01-01

    Full Text Available Baicalin is a flavonoid compound purified from the medicinal plant Scutellaria baicalensis Georgi and has been reported to stimulate surfactant protein (SP-A gene expression in human lung epithelial cell lines (H441. The aims of this study were to determine whether maternal baicalin treatment could increase lung surfactant production and induce lung maturation in fetal rats. This study was performed with timed pregnant Sprague-Dawley rats. One-day baicalin group mothers were injected intraperitoneally with baicalin (5 mg/kg/day on Day 18 of gestation. Two-day baicalin group mothers were injected intraperitoneally with baicalin (5 mg/kg/day on Days 17 and 18 of gestation. Control group mothers were injected with vehicle alone on Day 18 of gestation. On Day 19 of gestation, fetuses were delivered by cesarean section. Maternal treatment with 2-day baicalin significantly increased saturated phospholipid when compared with control group and total phospholipid in fetal lung tissue when compared with control and 1-day baicalin groups. Antenatal treatment with 2-day baicalin significantly increased maternal growth hormone when compared with control group. Fetal lung SP-A mRNA expression and maternal serum corticosterone levels were comparable among the three experimental groups. Maternal baicalin treatment increases pulmonary surfactant phospholipids of fetal rat lungs and the improvement was associated with increased maternal serum growth hormone. These results suggest that antenatal baicalin treatment might accelerate fetal rat lung maturation.

  5. Neurobehavioral response to increased treatment dosage in chronic, severe aphasia

    Directory of Open Access Journals (Sweden)

    Jennifer L Mozeiko

    2014-04-01

    •\tIncreased activation in S2’s bilateral inferior frontal gyrus following the second treatment session indicates that a second Treatment Period can influence continued neuroplastic change in severe, chronic aphasia. •\tS1 appears to show the most activation following Treatment Period I. It is possible that his greater lesion volume or site did not allow for benefit from a second dose to the same degree as S2. •\tActivation changes (or lack thereof in both cases corresponded with performance on the naming task in the scanner, reflecting the effect of treatment. •\tFor S2, neuroimaging supported the behavioral results which favor a second dose of ILAT. For S1, behavioral results, particularly in his consistent increases on the BNT, are not supported by either the behavioral results in the scanner or the BOLD response.

  6. Pioglitazone-induced congestive heart failure and pulmonary edema in a patient with preserved ejection fraction.

    Science.gov (United States)

    Jearath, Vaneet; Vashisht, Rajan; Rustagi, Vipul; Raina, Sujeet; Sharma, Rajesh

    2016-01-01

    Pioglitazone-induced heart failure is known in patients with underlying heart disease, but is not well documented in patients with normal left ventricular function. Pioglitazone has been very popular as it is an insulin sensitizer and insulin resistance is prevalent among Indians. Fluid retention exacerbates pre-existing heart failure or precipitates heart failure in a patient with underlying left ventricular dysfunction. However, pathogenesis of heart failure in a patient with normal left ventricular function is not known. Probably it is due to dose-related effect on pulmonary endothelial permeability, rather than alterations in left ventricular mass or ejection fraction. We report a patient who developed congestive heart failure and pulmonary edema with normal left ventricular function within 1 year of starting pioglitazone therapy. We have to be careful in monitoring all possible side effects during followup when patients are on pioglitazone therapy.

  7. Pioglitazone-induced congestive heart failure and pulmonary edema in a patient with preserved ejection fraction

    Science.gov (United States)

    Jearath, Vaneet; Vashisht, Rajan; Rustagi, Vipul; Raina, Sujeet; Sharma, Rajesh

    2016-01-01

    Pioglitazone-induced heart failure is known in patients with underlying heart disease, but is not well documented in patients with normal left ventricular function. Pioglitazone has been very popular as it is an insulin sensitizer and insulin resistance is prevalent among Indians. Fluid retention exacerbates pre-existing heart failure or precipitates heart failure in a patient with underlying left ventricular dysfunction. However, pathogenesis of heart failure in a patient with normal left ventricular function is not known. Probably it is due to dose-related effect on pulmonary endothelial permeability, rather than alterations in left ventricular mass or ejection fraction. We report a patient who developed congestive heart failure and pulmonary edema with normal left ventricular function within 1 year of starting pioglitazone therapy. We have to be careful in monitoring all possible side effects during followup when patients are on pioglitazone therapy. PMID:27127397

  8. Pioglitazone-induced congestive heart failure and pulmonary edema in a patient with preserved ejection fraction

    Directory of Open Access Journals (Sweden)

    Vaneet Jearath

    2016-01-01

    Full Text Available Pioglitazone-induced heart failure is known in patients with underlying heart disease, but is not well documented in patients with normal left ventricular function. Pioglitazone has been very popular as it is an insulin sensitizer and insulin resistance is prevalent among Indians. Fluid retention exacerbates pre-existing heart failure or precipitates heart failure in a patient with underlying left ventricular dysfunction. However, pathogenesis of heart failure in a patient with normal left ventricular function is not known. Probably it is due to dose-related effect on pulmonary endothelial permeability, rather than alterations in left ventricular mass or ejection fraction. We report a patient who developed congestive heart failure and pulmonary edema with normal left ventricular function within 1 year of starting pioglitazone therapy. We have to be careful in monitoring all possible side effects during followup when patients are on pioglitazone therapy.

  9. Influences of pioglitazone on quantity of endothelial progenitor cells and adiponectin level in patients with unstable angina pectoris complicating diabetes%吡格列酮对不稳定型心绞痛合并糖尿病患者内皮祖细胞数量及脂联素水平的影响

    Institute of Scientific and Technical Information of China (English)

    陈立东; 肖敏; 张绪国; 朱艳霞; 梁鹏飞; 邹兆坤

    2015-01-01

    treatment and 12 w after treatment, and EPCs were localized with CD34+/KDR+double labeling. The changes of quantity of EPCs and level of serum adiponectin were compared between 2 groups before and after treatment. Results The quantity of EPCs had no statistical difference between 2 groups before treatment (P>0.05). After treatment for 12 w, the quantity of EPCs increased significantly in pioglitazone group (0.023±0.010 vs. 0.051 ±0.012, P0.05). The quantity of EPCs was higher in pioglitazone group than that in control group 12 w after treatment (P0.05). The level of serum adiponectin was higher in pioglitazone group than that in control group 12 w after treatment (P<0.05). Conclusion Pioglitazone can improve the mobilization of EPCs and level of serum adiponectin in patients with UAP complicating T2DM.

  10. Increase in body weight after pramipexole treatment in Parkinson's disease.

    Science.gov (United States)

    Kumru, Hatice; Santamaria, Joan; Valldeoriola, Francesc; Marti, Maria J; Tolosa, Eduardo

    2006-11-01

    Body weight changes occur during the clinical course of Parkinson's disease (PD) and with surgical treatment, but the effect of dopaminergic treatment on weight is unknown. Body mass index (BMI), Hamilton depression scale score (HDS), and Unified Parkinson's Disease Rating Scale III (UPRS-III) were measured before and 3 months after starting pramipexole in 28 PD patients. Pramipexole produced a significant weight increase, as well as motor and mood improvement (P weight gain in PD.

  11. Pioglitazone (Actos) and bladder cancer: Legal system triumphs over the evidence.

    Science.gov (United States)

    Davidson, Mayer B

    2016-08-01

    In preclinical studies, pioglitazone was associated with bladder cancer in male rats (but not in female rats, mice dogs or monkeys). Because of this association, the Federal Drug Administration requested a large 10year epidemiological study to evaluate whether there was an association between bladder cancer and exposure to pioglitazone in patients. A 5-year interim report published in 2011 showed no significant association between ever vs never exposure to the drug but a significant association in patients exposed to pioglitazone for >2years. Importantly, the final 10year report did not confirm the 5year interim report finding no association between bladder cancer and pioglitazone, even after >4years of exposure to the drug. However, as would be expected, following the 5-year interim report, many epidemiological studies were carried out and civil litigation lawsuits began to be filed. Of the 23 epidemiological studies that have been published to date, 18 showed no association between bladder cancer and pioglitazone (5 with a combination of rosiglitazone and pioglitazone). Of the five that did show a significant association with pioglitazone, three could not be confirmed in the same population and in one of them there were significantly more risk factors for bladder cancer in the patients exposed to pioglitazone. In the fourth one, a significant association became non-significant when patients >79years were included. In the fifth one, detection bias was a major flaw. Currently, >11,000 legal cases have been filed, many of which claim emotional distress due to the fear of bladder cancer. To limit their legal costs, the pharmaceutical company has established a 2.4 billion dollar settlement pool. So much for evidence-based medicine.

  12. Effect of Pioglitazone on Serum Uric Acid Levels in Newly Diagnosed, Drug-Naïve Patients with Type 2 Diabetes.

    Science.gov (United States)

    Kutoh, Eiji; Hori, Tadataka

    2012-12-05

    Objectives. The aim of this study was to investigate the effect of pioglitazone on serum uric acid (UA) levels and several diabetic parameters in drug-naïve subjects with type 2 diabetes mellitus (T2DM). Patients and Methods. The patients (n = 68) received 7.5-30 mg/day pioglitazone monotherapy. They were divided into three groups based on their baseline UA levels (low, medium, and high). These parameters were followed for 12 weeks. Results. At baseline, HbA1c and fasting blood glucose (FBG) levels were in negative proportion to those of UA, while homeostasis model assessment-beta (HOMA-B) levels were in proportion to those of UA. Insulin, homeostasis model assessment-R (HOMA-R), and body mass index (BMI) levels had a tendency to be in proportion to those of UA. While similar glycemic effects were observed in all the groups, UA levels significantly decreased in the high UA group while they insignificantly increased in the low UA group. Multiple regression analysis revealed that the baseline UA level and age were the significant determinants for the changes of UA levels. In the high UA group, significant decreases of insulin and HOMA-R levels were observed, and their changes (Δ) were significantly correlated with those of UA. Other parameters including insulin, HOMA-R, HOMA-B, and BMI were also differentially regulated between these groups. Conclusions. These results indicate that (1) while similar glycemic effects were observed, distinct regulations of UA and other diabetic parameters were observed with pioglitazone depending on the baseline UA levels; (2) pioglitazone downregulated hyperuricemia by possibly relieving insulin resistance; and (3) the level of UA together with other parameters might provide some diabetic characteristics of the subjects.

  13. The bioflavonoid quercetin synergises with PPAR-γ agonist pioglitazone in reducing angiotensin-II contractile effect in fructose-streptozotocin induced diabetic rats.

    Science.gov (United States)

    Kunasegaran, Thubasni; Mustafa, Mohd Rais; Murugan, Dharmani Devi; Achike, Francis I

    2016-06-01

    This study investigated the effects of combined minimal concentrations of quercetin and pioglitazone on angiotensin II-induced contraction of the aorta from fructose-streptozotocin (F-STZ)-induced type 2 diabetic rats and the possible role of superoxide anions (O2(-)) and nitric oxide (NO) in their potential therapeutic interaction. Contractile responses to Ang II of aortic rings from Sprague-Dawley (SD) and F-STZ rats were tested following pre-incubation of the tissues in the vehicle (DMSO; 0.05%), quercetin (Q, 0.1 μM), pioglitazone (P, 0.1 μM) or their combination (P + Q; 0.1 μM each). The amount of superoxide anion was evaluated by lucigenin-enhanced chemiluminescence and dihydroethidium fluorescence, and NO by assay of total nitrate/nitrite, and 4-Amino-5-Methylamino-2',7'-Difluorofluorescein (DAF-FM) diacetate. The synergistic reduction of Ang II-induced contraction of diabetic but not normal aorta with minimally effective concentrations of P + Q occurs through inhibiting O2(-) and increasing NO bioavailability. This finding opens the possibility of maximal vascular protective/antidiabetic effects with low dose pioglitazone combined with quercetin, thus minimizing the risk of adverse effects.

  14. 吡格列酮对2型糖尿病患者血清脂联素、内脂素水平的影响%Effects of Pioglitazone on Serum Adiponectin and Visfatin Levels in Patients with Type 2 Diabetes Mellitus

    Institute of Scientific and Technical Information of China (English)

    汤佳珍; 杨治芳; 甘华侠; 刘建英; 章燕

    2011-01-01

    Objective To investigate the effects of pioglitazone on fasting serum adiponectin and visfatin levels in patients with type 2 diabetes mellitus(T2DM).Methods A case-control and a self-controlled study were conducted in 49 patients with newly diagnosed T2DM (T2DM group) and 50 healthy subjects (normal control group).Fasting serum adiponectin and visfatin levels were compared between the two groups,and the changes in the levels were measured after treatment with pioglitazone for 12 weeks.Results Compared with normal control group,pioglitazone induced a decrease in fasting serum levels of adiponectin and an increase in levels of visfatin [(12.3±2.8)mg · L-1 vs (6.4±l.1)mg· L-1]and [(13.5±9.2)μg · L-1 vs (36.2±10.6) μg · L-1], (P<0.01).Compared with the levels before treatment, adiponectin levels markedly increased 12 weeks after treatment with pioglitazone [(9.1 ±1.4)mg · L-1 vs (6.4±1.1)mg · L-1 , P<0.05], but no changes in visfatin levels were observed [(34.5 ±11.4)μg · L-1 vs (36.2±10.6)μg · L-1 ,P>0.05].Conclusion Pioglitazone can improve the decrease in serum adiponectin levels, but has no impact on the levels of serum visfatin in patients with T2DM.%目的 观察吡格列酮对2型糖尿病(T2DM)患者血清脂联素、内脂素的影响.方法 对新诊断的49例T2DM患者(T2DM组)和50例健康体检者(对照组)采用病例对照及治疗前后自身对照的方法,比较2组治疗前及T2DM组经吡格列酮治疗12周后空腹血清脂联素、内脂素的水平.结果 T2DM组治疗前与对照组相比,脂联素水平下降[(6.4±1.1)mg·L-1 vs (12.3±2.8)mg·L-1,P<0.01],内脂素水平升高[(36.2±10.6)μg·L-1 vs (13.5±9.2)μg·L-1,P<0.01];治疗后T2DM组与治疗前比较,脂联素明显升高[(9.1±1.4)mg·L-1 vs (6.4±1.1)mg·L-1,P<0.05],而内脂素无明显变化[(34.5 ±11.4)μg·L-1 vs (36.2±10.6)μg·L-1,fquP>0.05].结论 吡格列酮治疗可改善T2DM所导致的脂联素水平改变,而对内脂素水平无明显影响.

  15. Long-term pioglitazone therapy improves arterial stiffness in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Harashima, Keiichiro; Hayashi, Junichi; Miwa, Takashi; Tsunoda, Tooru

    2009-06-01

    Pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, not only improves insulin resistance and glycemic control, but may also have additional beneficial vascular effects in patients with type 2 diabetes mellitus. We investigated whether pioglitazone had an influence on arterial stiffness, which is an independent predictor of cardiovascular events, in 204 patients with type 2 diabetes mellitus. A prospective, nonrandomized, open-label trial was performed that involved 41 patients treated with pioglitazone, 46 patients receiving sulfonylureas, 67 patients on insulin, and 50 patients on diet/exercise only. The follow-up period was 56 +/- 3 months. Arterial stiffness was evaluated by using the arterial stiffness index (ASI), which was based on analysis of the pulse wave amplitude pattern obtained during automated blood pressure measurement in the upper limb. The 4 groups had a similar baseline ASI, which was greater than the reference range in each group. Although antidiabetic therapies improved hemoglobin A(1c) and low-density lipoprotein cholesterol, ASI only decreased significantly in the pioglitazone group. Thus, pioglitazone improved abnormal arterial stiffness in patients with type 2 diabetes mellitus via a mechanism beyond the metabolic improvement. These findings may have important clinical implications in the use of pioglitazone in patients with type 2 diabetes mellitus.

  16. Increases in body mass index following initiation of methadone treatment.

    Science.gov (United States)

    Fenn, Jennifer M; Laurent, Jennifer S; Sigmon, Stacey C

    2015-04-01

    Despite the clear efficacy of methadone for opioid dependence, one less desirable phenomenon associated with methadone may be weight gain. We examined changes in body mass index (BMI) among patients entering methadone treatment. A retrospective chart review was conducted for 96 patients enrolled in an outpatient methadone clinic for ≥ 6 months. The primary outcome of BMI was assessed at intake and a subsequent physical examination approximately 1.8 ± 0.95 years later. Demographic, drug use and treatment characteristics were also examined. There was a significant increase in BMI following intake (pmethadone treatment enrollment was associated with clinically significant weight gain, particularly among female patients. This study highlights the importance of efforts to help patients mitigate weight gain during treatment, particularly considering the significant health and economic consequences of obesity for individuals and society more generally.

  17. Randomized controlled study on efficacy of pioglitazone and metformin in treatment of patients with diabetes mellitus%吡格列酮与二甲双胍治疗糖尿病患者的疗效随机对照研究

    Institute of Scientific and Technical Information of China (English)

    吴艳萍

    2015-01-01

    Objective:To explore the therapeutic effect and safety of pioglitazone and metformin therapy in patients with type 2 diabetes.Methods:200 patients with diabetes were selected from January 2012 to December 2013.They were randomly divided into the observation group and the control group with 100 cases in each group.The observation group was treated with metformin,and the control group was treated with pioglitazone.We compared the level of blood glucose control,adverse reaction and complication rate to evaluate the therapeutic effect of two groups of patients.Results:There were statistically significant group differences in observation group and control group(F=13.60,P<0.01);the differences of blood glucose measurement time and group interaction were statistically significant(F=838.62,P<0.01);the hypoglycemic effect of pioglitazone was better than metformin;in the observation group, the incidence of adverse reaction was 1% ,which was significantly lower than the control group of 9% ,the difference was statistically significant( χ 2=5.70,P<0.05);in the observation group,the complication rate was 1% ,which was significantly lower than the control group of 9% ,the difference was statistically significant( χ 2=5.67,P<0.05).Conclusion:Glycemic control of metformin was obviously better than that of pioglitazone,and its adverse reaction and complication rate was low,curative effect was obviously better than pioglitazone,and it was worth the clinical promotion and application.%目的:探讨吡格列酮与二甲双胍治疗2型糖尿病患者的治疗效果及安全性.方法:2012年1月-2013年12月收治糖尿病患者200例,并随机分入观察组和对照组,各100例.观察组采用二甲双胍进行治疗,对照组采用吡格列酮进行治疗.观察比较两组患者血糖控制水平、不良反应及并发症发生率以评价两组患者的治疗效果.结果:观察组与对照组患者组别差异有统计学意义(F=13.60,P<0.01),

  18. 吡格列酮对高脂血症大鼠主动脉内皮细胞凋亡的作用%Effect of pioglitazone on aortic endothelial cell apoptosis in hyperlipidemic rats

    Institute of Scientific and Technical Information of China (English)

    李蓉; 董晓蕾; 赵凌杰; 蔡辉; 袁爱红

    2012-01-01

    than in control group. Serum levels of TG and TC were significantly decreased in pioglitazone treatment group than in model group (P = 0.000). ( 2) Compared with control group,the expression of Bax protein on aorta was significantly increased (P =0. 003) and the Bcl-2 protein and ratio of Bcl-2/Bax were markedly decreased in model group (P = 0.001 and 0.000,respectively). The expression of Bax protein was significantly lower and Bcl-2 protein and ratio of Bcl-2/Bax were significantly higher in pioglitazone treatment group than in model group,and apoptotic index of aortic intima was significantly lower than in model group [ ( 17.5633 ± 7.0584) vs. (6. 0475 ± 2. 2370),P = 0. 000 ] . Conclusions Pioglitazone can regulate the expression of apoptosis protein Bax and Bcl-2 in aorta and reduce aortic endothelial cell apoptosis in hyperlipidemia rats.

  19. Waiting Time Increases Risk of Attrition in Gambling Disorder Treatment

    DEFF Research Database (Denmark)

    Linnet, Jakob; Pedersen, Anders Sune

    2014-01-01

    completion in gambling disorder. We compared 48 gambling disorder sufferers with a 56% completion rate (21 non-completers and 27 completers). Binomial logistic regression analysis showed that waiting time from initial contact to the first session with a therapist was a significant predictor of risk...... of attrition: longer waiting times were associated with increased risk of attrition. Age, gender, or comorbidity was not associated with an increased risk of attrition. These data suggest that gambling disorder sufferers benefit from fast access to treatment, and that longer waiting time increases the risk...

  20. Steam treatment of digested biofibers for increasing biogas production.

    Science.gov (United States)

    Bruni, Emiliano; Jensen, Anders Peter; Angelidaki, Irini

    2010-10-01

    The aim of this study was to elucidate the effect of steam pretreatment on the biomethane potential of biofibers from digested manure. These biofibers were treated for 15 min with steam in a pressure vessel. The effect of steam treatment temperature, solids content, catalyst concentration and time of pre-soaking on the methane potential of the biofibers was determined. The highest increase of methane production from steam-treated biofibers compared to untreated biofibers was 67% and was achieved at 155 degrees C with addition of 2.1% w/w H2SO4. Also higher treatment temperatures (180 degrees C without addition of acid) improved the methane production, but only by 29% compared to untreated biofibers. Long pre-soaking treatment (24 h) and high acid concentration increased the risk of inhibition of the biogas process. The energy from the increased methane production after steam treatment was between 15 and 121 kW h (t WW)(-1) (wet weight of untreated biofibers).

  1. Peroxisome-proliferator-activated receptors gamma and peroxisome-proliferator-activated receptors beta/delta and the regulation of interleukin 1 receptor antagonist expression by pioglitazone in ischaemic brain.

    Science.gov (United States)

    Glatz, Torben; Stöck, Ivonne; Nguyen-Ngoc, Miriam; Gohlke, Peter; Herdegen, Thomas; Culman, Juraj; Zhao, Yi

    2010-07-01

    The imbalance between the production and release of interleukin-1 (IL-1) ligands, IL-1alpha, IL-1beta and IL-1 receptor antagonist (IL-1ra) in ischaemic brain exaggerates inflammatory responses and contributes to neuronal death. Cerebral ischaemia also upregulates the peroxisome-proliferator-activated receptor (PPAR) gamma. We studied in rats the effects of the PPARgamma agonist, pioglitazone, on the regulation of IL-1beta, IL-1ra and IL-1 receptor I (IL-1RI) expression in ischaemic brain after occlusion of the middle cerebral artery for 90 min. Pioglitazone or vehicle was infused intracerebroventricularly over a 5-day period before, during and 24 or 48 h after middle cerebral artery occlusion. The expression of IL-1beta, IL-1ra and IL-1RI in the peri-infarct cortex was investigated by immunohistochemistry, Western blotting and immunofluorescence staining. The mechanisms of the IL-1ra regulation by pioglitazone and the neuroprotection under excitotoxic neuronal injury were studied in primary cortical neurones expressing PPARgamma and PPAR beta/delta. Cerebral ischaemia increased the expression of IL-1beta, IL-1RI and IL-1ra in the ischaemic cortex. Pioglitazone reduced IL-1beta, but upregulated IL-1ra and increased the number of IL-1ra immunoreactive cells. In primary cortical neurones, pioglitazone stimulated the IL-1ra production via activation of the PPARbeta/delta, but prevented excitotoxic neuronal injury and death by a PPARgamma-dependent mechanism. Our data demonstrate that activation of PPARgamma and PPAR beta/delta by proglitazone in neurones triggers diverse neuroprotective mechanisms. The restoration of the equilibrium between I1-1beta and IL-1ra in ischaemic brain tissue limits IL-1beta signalling, reduces inflammatory responses and is an important mechanism by which thiazolidinediones improve the recovery from ischaemic stroke.

  2. Pioglitazone, a Peroxisome Proliferator-Activated Receptor γ Agonist, Suppresses Rat Prostate Carcinogenesis

    Science.gov (United States)

    Suzuki, Shugo; Mori, Yukiko; Nagano, Aya; Naiki-Ito, Aya; Kato, Hiroyuki; Nagayasu, Yuko; Kobayashi, Mizuho; Kuno, Toshiya; Takahashi, Satoru

    2016-01-01

    Pioglitazone (PGZ), a peroxisome proliferator-activated receptor γ agonist, which is known as a type 2 diabetes drug, inhibits cell proliferation in various cancer cell lines, including prostate carcinomas. This study focused on the effect of PGZ on prostate carcinogenesis using a transgenic rat for an adenocarcinoma of prostate (TRAP) model. Adenocarcinoma lesions as a percentage of overall lesions in the ventral prostate were significantly reduced by PGZ treatment in a dose-dependent manner. The number of adenocarcinomas per given area in the ventral prostate was also significantly reduced by PGZ treatment. The Ki67 labeling index in the ventral prostate was also significantly reduced by PGZ. Decreased cyclin D1 expression in addition to the inactivation of both p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)κB were detected in PGZ-treated TRAP rat groups. In LNCaP, a human androgen-dependent prostate cancer cell line, PGZ also inhibited cyclin D1 expression and the activation of both p38 MAPK and NFκB. The suppression of cultured cell growth was mainly regulated by the NFκB pathway as detected using specific inhibitors in both LNCaP and PC3, a human androgen-independent prostate cancer cell line. These data suggest that PGZ possesses a chemopreventive potential for prostate cancer. PMID:27973395

  3. INCREASING OF FALL RYE CORN FEEDING VALUE BY HYDROBARATHERNAL TREATMENT

    OpenAIRE

    2015-01-01

    The results of production experience on hydrobarathernal treatment fall rye grain feeding are presented in the article. It is determined that ater high temperature and pressure impact on fall rye grain in aqueous media dextrinization of starch specifically amylopectin occurs to monosugar in the form of glucose, therewith, sugar content increases more than in twice in comparison with parent grain. It is revealed that replacement of milled corn grain mixture to fall rye grain hydrolyzate in rat...

  4. Effect of low dose pioglitazone on glycemic control and insulin resistance in Type 2 diabetes: A randomized, double blind, clinical trial.

    Science.gov (United States)

    Rajagopalan, Sujit; Dutta, Pinaki; Hota, Debasish; Bhansali, Anil; Srinivasan, Anand; Chakrabarti, Amitava

    2015-09-01

    This study shows that pioglitazone 7.5 mg/day as an add-on therapy in Southeast Asian patients with Type 2 diabetes is safer and equally efficacious as the 15- and 30-mg doses of pioglitazone. Hence it is prudent to start pioglitazone therapy at a lower dose of 7.5 mg/day.

  5. Pharmacokinetics of pioglitazone, a thiazolidinedione derivative, in male Naeini (Iranian fat-tailed) sheep

    DEFF Research Database (Denmark)

    Ghoreishi, Sayed Mehdi; Rajaian, H.; Sheykhzade, Majid

    2012-01-01

    Pioglitazone (PGT) belongs to thiazolidinedione (TZD) family or insulin sensitizers that are potent ligands for peroxisome proliferator activated receptor gamma and are used in the treatment of type 2 diabetes mellitus. It has been shown that injection of TZD in cattle has some useful effects....../kg) was administered to five male sheep. Blood samples were collected at various time intervals, and PGT concentration was measured by a validated high-performance liquid chromatography method. The data obtained were best fitted into a two-compartment model for the IV route, and non-compartmental approach for oral...... route. The bioavailability of PGT was obtained to be approximately 62%. After IV injection of PGT, the elimination half-life (t 1/2ß), the volume of distribution at steady-state (V ss) and the elimination rate constant (k el) were obtained to be 4.04±0.88 h, 0.30±0.06 L/kg and 0.47±0.09 h-1...

  6. Pioglitazone Suppresses CXCR7 Expression To Inhibit Human Macrophage Chemotaxis through Peroxisome Proliferator-Activated Receptor γ.

    Science.gov (United States)

    Zhao, Duo; Zhu, Zhicheng; Li, Dan; Xu, Rihao; Wang, Tiance; Liu, Kexiang

    2015-11-17

    Cardiovascular disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Pioglitazone, the widely used thiazolidinedione, is shown to be efficient in the prevention of cardiovascular complications of T2DM. In this study, we report that pioglitazone inhibits CXCR7 expression and thus blocks chemotaxis in differentiated macrophage without perturbing cell viability or macrophage differentiation. In addition, pioglitazone-mediated CXCR7 suppression and chemotaxis inhibition occur via activating peroxisome proliferator-activated receptor γ (PPARγ) but not PPARα in differentiated macrophage. More importantly, pioglitazone therapy-induced PPARγ activation suppresses CXCR7 expression in human carotid atherosclerotic lesions. Collectively, our data demonstrate that pioglitazone suppresses CXCR7 expression to inhibit human macrophage chemotaxis through PPARγ.

  7. Prevention of diabetes with pioglitazone in ACT NOW: physiologic correlates.

    Science.gov (United States)

    Defronzo, Ralph A; Tripathy, Devjit; Schwenke, Dawn C; Banerji, Maryann; Bray, George A; Buchanan, Thomas A; Clement, Stephen C; Gastaldelli, Amalia; Henry, Robert R; Kitabchi, Abbas E; Mudaliar, Sunder; Ratner, Robert E; Stentz, Frankie B; Musi, Nicolas; Reaven, Peter D

    2013-11-01

    We examined the metabolic characteristics that attend the development of type 2 diabetes (T2DM) in 441 impaired glucose tolerance (IGT) subjects who participated in the ACT NOW Study and had complete end-of-study metabolic measurements. Subjects were randomized to receive pioglitazone (PGZ; 45 mg/day) or placebo and were observed for a median of 2.4 years. Indices of insulin sensitivity (Matsuda index [MI]), insulin secretion (IS)/insulin resistance (IR; ΔI0-120/ΔG0-120, ΔIS rate [ISR]0-120/ΔG0-120), and β-cell function (ΔI/ΔG × MI and ΔISR/ΔG × MI) were calculated from plasma glucose, insulin, and C-peptide concentrations during oral glucose tolerance tests at baseline and study end. Diabetes developed in 45 placebo-treated vs. 15 PGZ-treated subjects (odds ratio [OR] 0.28 [95% CI 0.15-0.49]; P IGT > T2DM) was associated with improvements in insulin sensitivity (OR 0.61 [95% CI 0.54-0.80]), IS (OR 0.61 [95% CI 0.50-0.75]), and β-cell function (ln IS/IR index and ln ISR/IR index) (OR 0.26 [95% CI 0.19-0.37]; all P < 0.0001). Of the factors measured, improved β-cell function was most closely associated with final glucose tolerance status.

  8. Clinical efficacy of glimepiride combined with pioglitazone on glycemic control in type 2 diabetes patients%格列美脲片联合吡格列酮治疗2型糖尿病患者的临床研究

    Institute of Scientific and Technical Information of China (English)

    哈斯; 孟帮柱; 巴图德力根

    2016-01-01

    Objective To evaluate the clinical efficacy of pioglitazone combined with glimepiride in treatment of type 2 diabetes mellitus.Methods A total of 100 patients with type 2 diabetes mellitus were ran-domly divided into treatment group( n=60) and control group( n=40).Patients in control group were treated with pioglitazone 15 mg per day be-fore breakfast.Patients in treatment group were treated with pioglitazone 15 mg, and glimepiride 1 mg per day before breakfast, if the blood glu-cose not controlled after 14 d, increase the dose to 2 mg.The blood glu-cose levels and adverse drug reactions of patients were recorded.The treatment lasted 28 d.Fasting plasma glucose, 2 h postprandial blood glucose, hemoglobin A1c(HbA1c) , fasting insulin and body mass index were determined and compared before and after treatment.Results The HbA1c, fasting glucose and fasting insulin were lower than those before treatment(P<0.05).The fasting insulin ,fasting glucose levels of treat-ment group were obviously lower than those of control group( P<0.05).Conclusion There was a good therapeutic effect for type 2 diabetes mellitus with pioglitazone combined with glimepiride, which can control blood sugar of patients fastly, safely and effectively.%目的:观察格列美脲和吡格列酮对2型糖尿病患者的临床疗效。方法100例血糖控制欠佳的2型糖尿病患者随机分为试验组60例和对照组40例。对照组早餐前口服吡格列酮片15 mg,每天1次;试验组早餐前口服吡格列酮片15 mg和格列美脲片,每天1次,格列美脲片始剂量为1 mg,14 d后若血糖控制不满意则剂量增至2 mg,随访观察28 d。比较2组患者治疗前后的空腹血糖、餐后2h血糖、糖化血红蛋白、空腹胰岛素、体重指数、肝功能及不良反应发生情况。结果治疗后,2组患者空腹血糖、糖化血红蛋白、空腹胰岛素均较疗前明显降低( P <0.05);试验组的空腹胰岛素和空腹

  9. Azithromycin (AZM) treatment increases survival of high risk corneal allotransplants

    Science.gov (United States)

    Medina, Carlos A.; Rowe, Alexander M.; Yun, Hongmin; Knickelbein, Jared E.; Lathrop, Kira L.; Hendricks, Robert L.

    2012-01-01

    Purpose To test the therapeutic efficacy of AZM, a macrolide antibiotic for prolonging murine “high risk” corneal allograft survival. Methods Fully MHC mismatched corneas were transplanted from C57BL/6 donors to BALB/c recipients with suture-induced vascularized “high risk” corneal beds. Recipient mice were either not treated or treated with topical AZM, oral AZM, or both. Evaluation of graft vascularization and clarity was performed in masked fashion. Lymph nodes were excised and analyzed for CD4, FoxP3, and CD44 by flow cytometry; and for T cell priming by proliferation and cytokine production in mixed lymphocyte cultures. Corneal whole mounts were evaluated by confocal microscopy. Results The incidence of graft rejection in the control group (81.8%) was significantly reduced by AZM treatment (18.2% topical, 21.7% oral, 33.3% topical + oral), although corneal vascularization was not affected by treatment. The frequency of corneas that retained complete clarity following transplantation was higher in the AZM treated groups. Reduced graft rejection in the AZM treated groups was not associated with a reduced allospecific T cell response or increased frequency of T regulatory cells. Conclusions AZM is effective in prolonging survival of “high risk” corneal allografts by an as yet undefined mechanism that does not appear to involve modulation of corneal neovascularization or allo-specific T cell priming. PMID:23407315

  10. Effects of pioglitazone on serum leptin and adiponectin in polycystic ovary syndrome patients with insulin resistance

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To investigate the effects of pioglitazone on serum leptin and adiponectin in polycystic ovary syndrome(PCOS)patients with insulin resistance(IR).Methods Thirty-five PCOS patients with IR were treated with pioglitazone 15mg/d for 12 weeks.The results of ovulation induction were observed.The changes of fasting plasma glucose(FPG),fasting serum insulin(FINS),serum levels of leptin,adiponectin,follicle-stimulating hormone(FSH),luteinizing hormone(LH),testosterone(T)and blood fat were examined at the ...

  11. Chronic fluoxetine treatment increases daytime melatonin synthesis in the rodent

    Directory of Open Access Journals (Sweden)

    Gillian W Reierson

    2009-09-01

    Full Text Available Gillian W Reierson, Claudio A Mastronardi, Julio Licinio, Ma-Li WongCenter on Pharmacogenomics, Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USAAbstract: Circadian rhythm disturbances can occur as part of the clinical symptoms of major depressive disorder and have been found to resolve with antidepressant therapy. The pineal gland is relevant to circadian rhythms as it secretes the hormone melatonin following activation of the cyclic adenosine monophosphate (cAMP signaling cascade and of arylalkylamine N-acetyltransferase (AA-NAT, the rate-limiting enzyme for its synthesis. Cyclic AMP is synthesized by adenylate cyclases (AC and degraded by phosphodiesterases (PDEs. Little is known about the contribution of the PDE system to antidepressant-induced alterations in pineal cAMP signaling and melatonin synthesis. In the present study we used enzyme immunoassay to measure plasma melatonin levels and pineal cAMP levels and as well as quantitative real-time polymerase chain reaction to measure pineal expression of PDE, AC, and AA-NAT genes in rats chronically treated with the prototypic antidepressant fluoxetine. We found elevated melatonin synthesis with increased pineal AA-NAT gene expression and daytime plasma melatonin levels and downregulated cAMP signaling with increased PDE and unchanged AC pineal gene expression, and decreased content of pineal cAMP. We conclude that chronic fluoxetine treatment increases daytime plasma melatonin and pineal AA-NAT gene expression despite downregulated pineal cAMP signaling in the rodent.Keywords: antidepressant, melatonin, pineal, nucleotides, cyclic, phosphodiesterase, rat

  12. Different skeletal effects of the peroxisome proliferator activated receptor (PPAR)alpha agonist fenofibrate and the PPARgamma agonist pioglitazone.

    Science.gov (United States)

    Syversen, Unni; Stunes, Astrid K; Gustafsson, Björn I; Obrant, Karl J; Nordsletten, Lars; Berge, Rolf; Thommesen, Liv; Reseland, Janne E

    2009-03-30

    All the peroxisome proliferator activated receptors (PPARs) are found to be expressed in bone cells. The PPARgamma agonist rosiglitazone has been shown to decrease bone mass in mice and thiazolidinediones (TZDs) have recently been found to increase bone loss and fracture risk in humans treated for type 2 diabetes mellitus. The aim of the study was to examine the effect of the PPARalpha agonist fenofibrate (FENO) and the PPARgamma agonist pioglitazone (PIO) on bone in intact female rats. Rats were given methylcellulose (vehicle), fenofibrate or pioglitazone (35 mg/kg body weight/day) by gavage for 4 months. BMC, BMD, and body composition were measured by DXA. Histomorphometry and biomechanical testing of excised femurs were performed. Effects of the compounds on bone cells were studied. The FENO group had higher femoral BMD and smaller medullary area at the distal femur; while trabecular bone volume was similar to controls. Whole body BMD, BMC, and trabecular bone volume were lower, while medullary area was increased in PIO rats compared to controls. Ultimate bending moment and energy absorption of the femoral shafts were reduced in the PIO group, while similar to controls in the FENO group. Plasma osteocalcin was higher in the FENO group than in the other groups. FENO stimulated proliferation and differentiation of, and OPG release from, the preosteoblast cell line MC3T3-E1. We show opposite skeletal effects of PPARalpha and gamma agonists in intact female rats. FENO resulted in significantly higher femoral BMD and lower medullary area, while PIO induced bone loss and impairment of the mechanical strength. This represents a novel effect of PPARalpha activation.

  13. Different skeletal effects of the peroxisome proliferator activated receptor (PPARα agonist fenofibrate and the PPARγ agonist pioglitazone

    Directory of Open Access Journals (Sweden)

    Nordsletten Lars

    2009-03-01

    Full Text Available Abstract Background All the peroxisome proliferator activated receptors (PPARs are found to be expressed in bone cells. The PPARγ agonist rosiglitazone has been shown to decrease bone mass in mice and thiazolidinediones (TZDs have recently been found to increase bone loss and fracture risk in humans treated for type 2 diabetes mellitus. The aim of the study was to examine the effect of the PPARα agonist fenofibrate (FENO and the PPARγ agonist pioglitazone (PIO on bone in intact female rats. Methods Rats were given methylcellulose (vehicle, fenofibrate or pioglitazone (35 mg/kg body weight/day by gavage for 4 months. BMC, BMD, and body composition were measured by DXA. Histomorphometry and biomechanical testing of excised femurs were performed. Effects of the compounds on bone cells were studied. Results The FENO group had higher femoral BMD and smaller medullary area at the distal femur; while trabecular bone volume was similar to controls. Whole body BMD, BMC, and trabecular bone volume were lower, while medullary area was increased in PIO rats compared to controls. Ultimate bending moment and energy absorption of the femoral shafts were reduced in the PIO group, while similar to controls in the FENO group. Plasma osteocalcin was higher in the FENO group than in the other groups. FENO stimulated proliferation and differentiation of, and OPG release from, the preosteoblast cell line MC3T3-E1. Conclusion We show opposite skeletal effects of PPARα and γ agonists in intact female rats. FENO resulted in significantly higher femoral BMD and lower medullary area, while PIO induced bone loss and impairment of the mechanical strength. This represents a novel effect of PPARα activation.

  14. Pioglitazone attenuates the severity of sodium taurocholate-induced severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Ping Xu; Xiao-Jiang Zhou; Ling-Quan Chen; Jiang Chen; Yong Xie; Long-Hua Lv; Xiao-Hua Hou

    2007-01-01

    AIM: To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-γ (PPARγ)ligand, on development of severe acute pancreatitis (SAP) and expression of nuclear factor-kappa B (NF-κB)and intercellular adhesion molecule-1 (ICAM-1) in the pancreas.METHODS: Male Sprague-Dawley (SD) rats (160-200 g)were randomly allocated into three groups (n = 18in each group): severe acute pancreatitis group,pioglitazone group, sham group. SAP was induced by retrograde infusion of 1 mL/kg body weight 5% sodium taurocholate (STC) into the biliopancreatic duct of male SD rats. Pioglitazone was injected intraperitoneally two hours piror to STC infusion. Blood and ascites were obtained for detecting amylase and ascitic capacity. Pancreatic wet/dry weight ratio, expression of NF-κB and ICAM-1 in pancreatic tissues were detected by immunohistochemical staining. Pancreatic tissue samples were stained with hematoxylin and eosin (HE)for routine optic microscopy.RESULTS: Sham group displayed normal pancreatic structure. SAP group showed diffuse hemorrhage,necrosis and severe edema in focal areas of pancreas.There was obvious adipo-saponification in abdominal cavity. Characteristics such as pancreatic hemorrhage,necrosis, severe edema and adipo-saponification were found in pioglitazone group, but the levels of those injuries were lower in pioglitazone group than those in SAP group. The wet/dry pancreatic weight ratio,ascetic capacity, serum and ascitic activities of anylase in the SAP group were significantly higher than those in the sham group and pioglitazone group respectively (6969.50 ± 1368.99 vs 2104.67 ± 377.16, 3.99 ± 1.22 vs 2.48 ± 0.74, P < 0.01 or P < 0.05). According to Kusske criteria, the pancreatic histologic score showed that interstitial edema, inflammatory infiltration,parenchyma necrosis and parenchyma hommorrhage in SAP group significantly differed from those in the sham group and pioglitazone group (7.17 ± 1.83 vs 0.50 ±0.55, 7

  15. No improvement of high-density lipoprotein (HDL) vasorelaxant effect despite increase in HDL cholesterol concentration in type 2 diabetic patients treated with glitazones.

    Science.gov (United States)

    Perségol, Laurence; Duvillard, Laurence; Monier, Serge; Brindisi, Marie-Claude; Bouillet, Benjamin; Petit, Jean-Michel; Vergès, Bruno

    2014-10-01

    High-density lipoproteins (HDLs) from type 2 diabetic patients are unable to counteract the inhibitory effect of oxidized low-density lipoproteins (ox-LDLs) on vasorelaxation. We hypothesized that glitazones, which improve glycemic control and dyslipidemia, could correct this abnormality. We compared the ability of HDL from controls (n = 12) and from type 2 diabetic patients before and after 6 months of treatment with either rosiglitazone (n = 11) or pioglitazone (n = 8) to counteract the inhibitory effect of ox-LDL on vasodilatation of rabbit aorta rings. Rosiglitazone induced a decrease in hemoglobin A1c (7.7% ± 1.1% vs 9.8% ± 1.0%, P = .003) and an increase in HDL cholesterol (1.14 ± 0.32 vs 0.98 ± 0.24 mmol/L, P = .033). Pioglitazone induced a decrease in hemoglobin A1c (8.3% ± 2.5% vs 9.5% ± 3.2%, P = .068) and serum triglycerides (1.58 ± 0.89 vs 2.03 ± 0.70 mmol/L, P = .069) and an increase in HDL cholesterol (1.39 ± 0.22 vs 1.14 ± 0.22 mmol/L, P = .018). The triglyceride content of HDL was unchanged by rosiglitazone and was decreased by 25% (P = .068) by pioglitazone. HDL from controls counteracted the inhibitory effect of ox-LDL on vasodilatation (maximal relaxation [Emax] = 74.4% ± 3.5% vs 51.9% ± 3.3%, P = .0029), whereas HDL from type 2 diabetic patients did not (Emax = 51.7% ± 5.8% vs 52.3% ± 4.6% [P = .66] and 52.7% ± 5.5% vs 51.9% ± 4.5% [P = .78] for the rosiglitazone and pioglitazone group, respectively). Rosiglitazone or pioglitazone did not improve Emax (58.6% ± 5.9% vs 52.3% ± 4.6% [P = .15] and 49.3% ± 6.5% vs 51.9% ± 4.5% [P = .48], respectively). Glitazones increased the concentration of HDL cholesterol without restoring the ability of HDL particles to protect the endothelium from oxidative stress-induced dysfunction, meaning that HDL remained dysfunctional with impaired antiatherogenic properties.

  16. Comparative evaluation of effects of combined oral anti-diabetic drugs (sulfonylurea plus pioglitazone and sulfonylurea plus metformin over lipid parameters in type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    Sukanta Sen

    2013-06-01

    Full Text Available Background: Type 2 diabetes is associated with significant cardiovascular morbidity and mortality. Dyslipidemia, which affects almost 50% of patients with type 2 diabetes, is a cardiovascular risk factor characterized by elevated triglyceride levels, low high-density lipoprotein (HDL cholesterol levels, and a preponderance of small, dense, low-density lipoprotein (LDL particles. In addition to their glucose-lowering properties, oral anti-diabetic agents may have effects on lipid levels, especially triglycerides (TGs, HDL-C, LDL-C and total cholesterol levels. Methods: A prospective, open-labeled, randomized, parallel-group study was carried out in sizable number of patients (n=40 of established type 2 diabetes on combined oral anti-diabetic drugs, to investigate the effects of combined oral anti-diabetic on lipid parameters who was not receiving any hypolipidemic agent in addition. Results: Statistically significant mean reduction of triglycerides (TGs of 25.1mg/dl (a 15.30% reduction from baseline value and by 13.5 mg/dl (a 8.94% reduction from baseline value in the SU (sulfonylurea plus PIO (pioglitazone and SU plus MET (metformin group respectively. Present study also shows improvement in HDL cholesterol with SU plus PIO group by 13.18% which is almost twice that observed in SU plus MET group (8.06%. Present study also shows increase in LDL cholesterol with SU plus PIO group by 2.10%, is just opposite to SU plus MET group (4.92 % decrease. With SU plus PIO group, a statistically significant mean reduction of total cholesterol (TC of 8.33mg/dl (5.14 % decrease and by 7.62 mg/dl (4.28% decrease in the SU plus MET group. Conclusions: Pioglitazone, a thiazolidinedione, has been shown to improve the lipid profile in patients with type 2 diabetes by increasing HDL-C levels and by decreasing triglyceride and total cholesterol levels in monotherapy or combination regimens with sulfonylurea. Metformin also has been shown to reduce LDL-C, TC, and TG

  17. Pleiotropic effects of thiazolidinediones: implications for the treatment of patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Defronzo, Ralph A; Mehta, Rucha J; Schnure, Joel J

    2013-04-01

    similar effects on glycemic control, pioglitazone and rosiglitazone appear to have different effects on cardiovascular outcomes. Rosiglitazone has been associated with an increased risk of myocardial infarction, and its use in the United States is restricted because of cardiovascular safety concerns.

  18. Does carbon reduction increase sustainability? A study in wastewater treatment.

    Science.gov (United States)

    Sweetapple, Christine; Fu, Guangtao; Butler, David

    2015-12-15

    This study investigates the relationships between carbon reduction and sustainability in the context of wastewater treatment, focussing on the impacts of control adjustments, and demonstrates that reducing energy use and/or increasing energy recovery to reduce net energy can be detrimental to sustainability. Factorial sampling is used to derive 315 control options, containing two different control strategies and a range of sludge wastage flow rates and dissolved oxygen setpoints, for evaluation. For each, sustainability indicators including operational costs, net energy and multiple environmental performance measures are calculated. This enables identification of trade-offs between different components of sustainability which must be considered before implementing energy reduction measures. In particular, it is found that the impacts of energy reduction measures on sludge production and nitrogen removal must be considered, as these are worsened in the lowest energy solutions. It also demonstrates that a sufficiently large range of indicators need to be assessed to capture trade-offs present within the environmental component of sustainability. This is because no solutions provided a move towards sustainability with respect to every indicator. Lastly, it is highlighted that improving the energy balance (as may be considered an approach to achieving carbon reduction) is not a reliable means of reducing total greenhouse gas emissions.

  19. Treatment of essential telangiectasia: effects of increasing concentrations of polidocanol.

    Science.gov (United States)

    Norris, M J; Carlin, M C; Ratz, J L

    1989-04-01

    A double-blind, double-paired comparison study was performed to evaluate the effects of increasing concentrations of polidocanol in the sclerotherapy of essential telangiectasias of the legs. Polidocanol 0.25%, 0.50%, 0.75%, and 1.0% were compared with regard to clinical effectiveness, safety, and patient acceptance. All dosages were well tolerated by the patients. There were no allergic reactions to polidocanol and no cases of superficial ulceration nor necrosis. Among those whose veins cleared, there was little difference in time to clearing for the four concentrations, which averaged three to four treatment sessions. No statistically significant differences existed among the four dosages with respect to level of improvement, itching, or neovascularization. Polidocanol 0.75% and 1.0%, however, caused more side effects noted by patients and induced more hyperpigmentation than did the lower concentrations. Polidocanol 0.25% yielded the lowest percentage of patients whose veins cleared. The 0.50% solution was the most effective concentration for total overall clearing of the types of vessels treated in this study. From this information it appears that 0.50% polidocanol may be the sclerosing agent of choice.

  20. A comparison of glycemic control, water retention, and musculoskeletal effects of balaglitazone and pioglitazone in diet-induced obese rats

    DEFF Research Database (Denmark)

    Henriksen, Kim; Byrjalsen, Inger; Nielsen, Rasmus H

    2009-01-01

    : vehicle, pioglitazone 10 mg/kg, pioglitazone 30 mg/kg, balaglitazone 5 mg/kg, balaglitazone 10 mg/kg. At day -7, 21 and 42 fasting serum samples were collected and whole body tissue composition was evaluated by MR scanning. Food intake and bodyweights were monitored during the study period. At day 42...... of equipotent glucose lowering concentrations of the partial PPARgamma agonist balaglitazone and the full agonist pioglitazone in male diet-induced obese rats, to investigate effects on bone formation, fluid retention and fat accumulation. Sixty male dio induced obese rats were divided into five categories...

  1. Effects of pioglitazone on the expression of AdipoR mRNA of aorta in hyperlipidemia rats%吡格列酮对高脂血症大鼠主动脉脂联素受体mRNA表达的影响

    Institute of Scientific and Technical Information of China (English)

    徐玉顺; 沈思钰; 蔡辉

    2012-01-01

    ), and the serum APN in Pio group was obviously increased (P<0. 05). Treatment with pioglitazone enhanced the mRNA expression of both AdipoRl and AdipoR2(P<0. 05 or P<0. 01). Conclusions Decreased expression of AdipoR may involve in vascular impairment in rats with high-fat diet induced hyperlipidemia. Pioglitazone may exerte a significant vascular protective effect in hyperlipidemia rats, which may relate to increased serum APN and expression of AdipoR in vascular wall and contribute to their anti-atherosclerosis effect.

  2. Effect of pioglitazone on the abrogated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart

    Directory of Open Access Journals (Sweden)

    Dhiraj Mittal

    2016-01-01

    Conclusion: Cardioprotective effect of IPC gets lost in hyperlipidemic rat heart. The results suggest that perfusion of pioglitazone restored the cardioprotective effect of IPC in hyperlipidemic rat heart, an effect that may be via PI3K and mTOR.

  3. Pioglitazone, an anti-diabetic drug requires sustained MAPK activation for its anti-tumor activity in MCF7 breast cancer cells, independent of PPAR-γ pathway.

    Science.gov (United States)

    Kole, Labanyamoy; Sarkar, Mrinmoy; Deb, Anwesha; Giri, Biplab

    2016-02-01

    The thiazolidinedione (TZD) class of peroxisome proliferator-activated receptor gamma (PPAR-γ) ligands are known for their ability to induce adipocyte differentiation, to increase insulin sensitivity including anticancer properties. But, whether or not upstream events like MAPK activation or PPAR-γ signaling are involved or associated with this anticancer activity is not well understood in breast cancer cells. The role of MAPK and PPAR pathways during the pioglitazone (Pio) induced PPAR-γ independent anticancer activity in MCF7 cells has been focused here. The anticancer activity of Pio has been investigated in breast cancer cells in vitro. Anti-tumor effects were assessed by alamar blue assay, Western blot analysis, cell cycle analysis, and annexin V-FITC/PI binding assay by flow cytometry, Hoechst staining and luciferase assay. The anticancer activity of Pio is found to be correlating with the up regulation of CDKIs (p21/p27) and down regulation of CDK-4. This study demonstrates that the induction of CDKIs by Pio is due to the sustained activation of MAPK. The Pio-mediated activation of MAPK is transmitted to activate ELK-1 and the related anti-proliferation is blocked by MEK inhibitor (PD-184352). Pio suppresses the proliferation of MCF7 cells, at least partly by a PPAR-γ-independent mechanism involving the induction of p21 which in turn requires sustained activation of MAPK. These findings implicate the utility of Pio in the treatment of PPAR positive or negative human cancers and the development of a new class of compounds to enhance the effectiveness of Pio. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  4. A study on the short-term effect of cafeteria diet and pioglitazone on insulin resistance and serum levels of adiponectin and ghrelin.

    Science.gov (United States)

    Colombo, G; Bazzo, M L; Nogueira, C L; Colombo, M D H P; Schiavon, L L; d'Acampora, A J

    2012-10-01

    The interaction between ghrelin and adiponectin is still controversial. We investigated the effect of cafeteria diet and pioglitazone on body weight, insulin resistance, and adiponectin/ghrelin levels in an experimental study on male Wistar rats. The animals were divided into four groups of 6 rats each, and received balanced chow with saline (CHOW-O) or pioglitazone (CHOW-P), or a cafeteria diet with saline (CAFE-O) or pioglitazone (CAFE-P). The chow/cafeteria diets were administered for 35 days, and saline/pioglitazone (10 mg · kg body weight(-1) · day(-1)) was added in the last 14 days prior to euthanasia. CAFE-O animals had a higher mean final weight (372.5 ± 21.01 g) than CHOW-O (317.66 ± 25.11 g, P = 0.017) and CHOW-P (322.66 ± 28.42 g, P = 0.035) animals. Serum adiponectin levels were significantly higher in CHOW-P (55.91 ± 20.62 ng/mL) than in CHOW-O (30.52 ± 6.97 ng/mL, P = 0.014) and CAFE-O (32.54 ± 9.03 ng/mL, P = 0.027) but not in CAFE-P. Higher total serum ghrelin levels were observed in CAFE-P compared to CHOW-P animals (1.65 ± 0.69 vs 0.65 ± 0.36 ng/mL, P = 0.006). Likewise, acylated ghrelin levels were higher in CAFE-P (471.52 ± 195.09 pg/mL) than in CHOW-P (193.01 ± 87.61 pg/mL, P = 0.009) and CAFE-O (259.44 ± 86.36 pg/mL, P = 0.047) animals. In conclusion, a cafeteria diet can lead to a significant weight gain. Although CAFE-P animals exhibited higher ghrelin levels, this was probably related to food deprivation rather than to a direct pharmacological effect, possibly attenuating the increase in adiponectin levels.

  5. Seroma indicates increased risk of lymphedema following breast cancer treatment

    DEFF Research Database (Denmark)

    Toyserkani, Navid Mohamadpour; Jørgensen, Mads Gustaf; Haugaard, Karen

    2017-01-01

    Introduction Lymphedema is one of the most serious complications following breast cancer treatment. While many risk factors are well described the role of seroma formation has recently produced mixed results. Therefore, we aimed to evaluate if seroma is a risk factor for development of lymphedema...... in one of the largest retrospective cohort studies. Material and methods We included all patients with unilateral breast cancer treated in the period of 2008-2014. Data regarding treatment and breast cancer characteristics were retrieved from the national breast cancer registry. Data regarding lymphedema...... treatment and seroma aspirations were retrieved from local treatment codes. Results In total 1822 patients were included of which 291 developed lymphedema. Multivariate cox regression analysis showed that seroma was an independent risk factor (HR 1.92 CI 1.30-2.85, p= 0.001). Other independent risk factors...

  6. Early postnatal dexamethasone treatment and increased incidence of cerebral palsy

    National Research Council Canada - National Science Library

    Shinwell, E S; Karplus, M; Reich, D; Weintraub, Z; Blazer, S; Bader, D; Yurman, S; Dolfin, T; Kogan, A; Dollberg, S; Arbel, E; Goldberg, M; Gur, I; Naor, N; Sirota, L; Mogilner, S; Zaritsky, A; Barak, M; Gottfried, E

    2000-01-01

    To study the long term neurodevelopmental outcome of children who participated in a randomised, double blind, placebo controlled study of early postnatal dexamethasone treatment for prevention of chronic lung disease...

  7. Toll-like Receptor 4 Signaling Pathway in the Protective Effect of Pioglitazone on Experimental Immunoglobulin A Nephropathy

    Directory of Open Access Journals (Sweden)

    Jia-Nan Zou

    2017-01-01

    Conclusions: Our study proves that inflammation mediated by TLR4 signaling pathway is involved in the progression of IgAN in rat models. Moreover, pioglitazone can inhibit the expression of TLR4 in IgAN.

  8. 吡格列酮和非诺贝特对高脂饮食大鼠胰岛细胞内信号分子的影响%Effects of fenofibrate and pioglitazone on expressions of intracellular signaling molecules in pancreatic islet of high-fat diet-fed rats

    Institute of Scientific and Technical Information of China (English)

    冯婷; 杨波; 田浩明

    2008-01-01

    Objective To observe the effects of fenofibrate and pioglitazone on the expressions of PPAR- α, PPAR-γ, and intracellular signaling molecules in pancreatic islets of obese rats induced by high-fat diets. Methods SD obese rat models were established with high-fat diet, and 40 male rats were assigned to 4 groups including high-fat diet (HF group), high-fat diet with fenofibrate (FF group), pioglitazone (FP group) treatment, and control rats with normal diet (NC group). After 8 weeks intervention, immunohistochemistry was performed to evaluate the expressions of various proteins in islets; At the same time, islets mass were scored in tissue slides. Results Islets mass enlarged in HF group. The compositions of islet cells were the same as the control. The expression of insulin was lower in HF group than the control, but after using pioglitazone, less islets mass and more insulin expression were found in FP group. Compared with the control group, expressions of PPAR-α, PPAR-γ protein were reduced in HF group, and the expression of PPAR-α protein increased in FF group, and the expression of PPAR-γ protein was increased in FP group. The levels of NF-кB, p38 mitogen-activated protein kinase (MAPK), ERK1 proteins increased significantly in HF group, the expressions of NF-кB, p38 MAPK decreased in FF and FP groups, and the level of ERK1 decreased only in FP group, the protein level of I-кB showed no difference among control, HF group, and FF groups. Conclusion Fenofibrate and pioglitazone may partially protect islet cells function and improve survival by correcting the disturbance of intracellular signaling molecules.%目的 观察吡格列酮和非诺贝特对高脂饮食大鼠胰岛内PPAR-α、-γ和细胞内信号分子的影响.方法 40只雄性SD大鼠随机分为4组:空白对照组(NC)、单纯高脂饮食组(HF)、高脂+非诺贝特组(FF)、高脂+吡格列酮组(FP).HE染色测定胰岛面积;免疫组织化学方法检测胰岛

  9. 吡格列酮对小鼠皮下、内脏脂肪棕色化的差异作用%The different roles of Pioglitazone in fat browning

    Institute of Scientific and Technical Information of China (English)

    李玉洁; 刘娟; 毕建华; 丁国宪

    2013-01-01

    目的:探讨吡格列酮对小鼠皮下、内脏脂肪棕色化不同作用及其机制.方法:取C57BL/5J小鼠皮下及内脏前脂肪细胞原代培养,诱导分化同时加吡格列酮刺激直至分化成熟后,RT-PCR检测棕色脂肪相关功能基因的mRNA表达水平.结果:在皮下脂肪中吡格列酮组较对照组棕色脂肪功能基因均明显表达上调(P< 0.05),而内脏脂肪对照组和吡格列酮组差异无统计学意义(P>0.05).结论:吡格列酮可促进小鼠皮下脂肪棕色化改变,但对内脏脂肪无作用.%Objective:To explore the role of Pioglitazone in the browning of both subcutaneous and visceral adipose tissue.Methods:Primary subcutaneous and visceral adipocytes were isolated from C57BL/5J mice and induced for differentiation.The primary cells were stimulated with 2.5 μmol/L Pioglitazone or vehicle throughout the whole induction period.Then the expression of either white fat or brown fat relative genes were observed by RT-PCR.Results:Pioglitazone could cause a significant increase of brown fat marker genes in the subcutaneous adipose tissue instead of the visceral adipose.Conclusion:Pioglitazone can promote a "white to brown" change in the subcutaneous adipose tissue instead of the visceral adipose.

  10. The influence of nicotine on pioglitazone encapsulation into carbon nanotube: the investigation of molecular dynamic and density functional theory.

    Science.gov (United States)

    Zaboli, Maryam; Raissi, Heidar

    2017-02-01

    In this work, molecular dynamics simulations of the insertion of pioglitazone into the nanotube with chirality (10, 10) at 400 K and 1 bar in the presence and absence of nicotine molecules and in different drug concentrations have been studied. The main aim is consideration of the effect of nicotine in the drug encapsulation process. The results indicate that encapsulation of pioglitazone could be attributed to the water flow via van der Waals and hydrophilic interactions. Because of the existence of the partial π-π interactions between aromatic rings of pioglitazone and the conjugated aromatic rings of nanotube, pioglitazone molecule can enter inside the nanotube. Some physical properties such as hydrogen bonding, number of contacts, also, the diffusion coefficient of the pioglitazone and water molecules, and variation of the center of mass have been calculated during the simulation. Furthermore, computing the electronic structure has also been done on model systems for quantitative determination of the adsorption energy (Eads). The B3LYP/6-31G* level calculations on four different configurations of pioglitazone/carbon nanotube (CNT) and nicotine/CNT show that the interaction of drug with the inside of the nanotube is stronger than the other forms.

  11. Smoking increases the risk of relapse after successful tuberculosis treatment

    Science.gov (United States)

    d’Arc Lyra Batista, Joanna; de Fátima Pessoa Militão de Albuquerque, Maria; de Alencar Ximenes, Ricardo Arraes; Rodrigues, Laura Cunha

    2008-01-01

    Background Recent tobacco smoking has been identified as a risk factor for developing tuberculosis, and two studies which have investigated its association with relapse of tuberculosis after completion of treatment had conflicting results (and did not control for confounding). The objective of this study was to investigate risk factors for tuberculosis relapse, with emphasis on smoking. Methods A cohort of newly diagnosed TB cases was followed up from their discharge after completion of treatment (in 2001–2003) until October 2006 and relapses of tuberculosis ascertained during that period. A case of relapse was defined as a patient who started a second treatment during the follow up. Results Smoking (OR 2.53, 95% CI 1.23–5.21) and living in an area where the family health program was not implemented (OR 3.61, 95% CI 1.46–8.93) were found to be independently associated with relapse of tuberculosis. Conclusions Our results establish that smoking is associated with relapse of tuberculosis even after adjustment for the socioeconomic variables. Smoking cessation support should be incorporated in the strategies to improve effectiveness of Tuberculosis Control Programs. PMID:18556729

  12. 吡格列酮联合放射治疗对小鼠结肠癌的抑制作用%Effects of pioglitazone combined with radiotherapy on colon carcinoma xenograft in mice

    Institute of Scientific and Technical Information of China (English)

    马卫平; 李金利

    2012-01-01

    combined with pioglitazone treated group could decrease the volume of tumor (P =0.008,P =0.001,P =0.001).Compared with pioglitazone treated group,the effect of radiotherapy group or radiotherapy combined with pioglitazone treated group was more evident (P =0.026,P =0.018).Contrasted with radiotherapy group,radiotherapy combined with pioglitazone treated group had no significant difference (P =0.335).The tumor inhibition rates of pioglitazone treated group,radiotherapy group and radiotherapy combined with pioglitazone treated group were 46.30 %,68.60 % and 70.01%.The pathological varieties of tumor were obvious.Conclusion Pioglitazone,radiotherapy and radiotherapy combined with pioglitazone could inhibit the growth of tumor.PPARγ is a new target for tumor treatment.

  13. Effects of increasing age, dosage, and duration of PTH treatment on BMD increase--a meta-analysis

    DEFF Research Database (Denmark)

    Schwarz, Peter; Jorgensen, Niklas Rye; Mosekilde, Leif;

    2012-01-01

    We studied the effects of increasing age, dosage, and duration of parathyroid hormone (PTH) treatment on changes in bone mineral density (BMD). Randomized placebo controlled trials on PTH treatment in men or women were retrieved from PubMed (1951 to present), Web of Science (1945 to present...

  14. Patients at increased fracture risk: identification and pharmacological treatment

    NARCIS (Netherlands)

    Klop, C.

    2016-01-01

    Fragility fractures are common and are associated with a substantial burden for patients and the healthcare system. Hip fractures in particular are associated with increased morbidity, institutionalisation, and even mortality with a mortality rate between 20-30% in the first year. This burden is inc

  15. Pioglitazone and bladder cancer in human studies: is it diabetes itself, diabetes drugs, flawed analyses or different ethnicities?

    Science.gov (United States)

    Tseng, Chin-Hsiao

    2012-03-01

    This article reviews human observations on pioglitazone and bladder cancer risk. The PROspective pioglitAzone Clinical Trial In macroVascular Events trial showed an imbalance in bladder cancer between users of pioglitazone and placebo (14 versus six cases, p = 0.069). However, after excluding bladder cancer probably ascribed to other etiology, a blind assessment concluded that the imbalance might not be related to pioglitazone. Epidemiologic studies conducted in the United States and France using insurance databases independently suggested that pioglitazone use for >2 years might confer a 20%-40% higher risk. Another study evaluating bladder cancer risk in diabetic patients using the National Health Insurance in Taiwan did not find any incident bladder cancer case among 422 pioglitazone users for a follow-up of up to 3 years. Because observational studies may suffer from selection and information bias, and inadequate adjustment for confounders may inflate the estimated risk, causal inference from these studies should be interpreted with caution. While investigating cancer risk associated with a medication, indication bias should also be attended, especially when the medication is used at a late stage of the disease. Because pioglitazone is usually a second or third line antidiabetic agent, the users are always characterized by older age, longer diabetes duration, poorer glycemic control, and higher rates of complications and comorbidities. Biased estimates will also result if these differences are not appropriately addressed in the analyses. Current evidence neither concludes nor excludes a causal role of pioglitazone on bladder cancer. Clinical trials aiming at evaluating the risk of cancer associated with a medication is not ethical and may not be expected to provide an answer on the issue of pioglitazone-related bladder cancer. However, a meta-analysis using all available clinical trials to compare the bladder cancer risk between pioglitazone and comparators

  16. Geraniol, alone and in combination with pioglitazone, ameliorates fructose-induced metabolic syndrome in rats via the modulation of both inflammatory and oxidative stress status.

    Directory of Open Access Journals (Sweden)

    Sherehan M Ibrahim

    Full Text Available Geraniol (GO potent antitumor and chemopreventive effects are attributed to its antioxidant and anti-inflammatory properties. In the current study, the potential efficacy of GO (250 mg/kg in ameliorating metabolic syndrome (MetS induced by fructose in drinking water was elucidated. Moreover, the effect of pioglitazone (5 and 10 mg/kg; PIO and the possible interaction of the co-treatment of GO with PIO5 were studied in the MetS model. After 4 weeks of treatment, GO and/or PIO reduced the fasting blood glucose and the glycemic excursion in the intraperitoneal glucose tolerance test. GO and PIO5/10 restrained visceral adiposity and partly the body weight gain. The decreased level of peroxisome proliferator activated receptor (PPAR-γ transcriptional activity in the visceral adipose tissue of MetS rats was increased by single treatment regimens. Though GO did not affect MetS-induced hyperinsulinemia, PIO5/10 lowered it. Additionally, GO and PIO5/10 suppressed glycated hemoglobin and the receptor for advanced glycated end products (RAGE. These single regimens also ameliorated hyperuricemia, the disrupted lipid profile, and the elevated systolic blood pressure evoked by MetS. The rise in serum transaminases, interleukin-1β, and tumor necrosis factor-α, as well as hepatic lipid peroxides and nitric oxide (NO was lowered by the single treatments to different extents. Moreover, hepatic non-protein thiols, as well as serum NO and adiponectin were enhanced by single regimens. Similar effects were reached by the combination of GO with PIO5; however, a potentiative interaction was noted on fasting serum insulin level, while synergistic effects were reflected as improved insulin sensitivity, as well as reduced RAGE and triglycerides. Therefore, GO via the transcriptional activation of PPAR-γ reduces inflammation and free radical injury produced by MetS. Thereby, these effects provide novel mechanistic insights on GO management of MetS associated critical

  17. Insulin treatment increases myocardial ceramide accumulation and disrupts cardiometabolic function

    OpenAIRE

    2015-01-01

    Background States of hyperinsulinemia, particularly insulin resistance and type 2 diabetes mellitus, are becoming remarkably common, with roughly half a billion people likely to suffer from the disorder within the next 15 years. Along with this rise has been an associated increased burden of cardiovascular disease. Considering type 2 diabetics treated with insulin are more likely to suffer from heart complications, we sought to determine the specific effect of insulin on ceramide-dependent ca...

  18. RP-HPLC METHOD FOR SIMULTANEOUS ESTIMATION OF SEXAGLIPTIN AND PIOGLITAZONE IN TABLETS

    Directory of Open Access Journals (Sweden)

    M.Sarat

    2012-05-01

    Full Text Available A simple, selective, accurate high Performance Liquid Chromatographic (HPLC method was developed and validated for the analysis of Sexagliptin and Pioglitazone. Chromatographic separation achieved isocratically on a C18 column [Use Inertsil C18, 5m , 150 mm x 4.6 mm] utilizing a mobile phase of acetonitrile/phosphate buffer (60:40, v/v, pH 7.0 at a flow rate of 0.8 ml/min with UV detection at 260nm.Aceclofenac was used as an internal standard. The retention time of Sexagliptin, pioglitazone and aceclofenac was 2.48, 4.45 and 6.34 min respectively. The developed method was validated in terms of accuracy, precision, linearity, limit of detection, limit of quantitation.This study aimed at developing and validating an HPLC method, being simple, accurate and selective, and the proposed method can be used for the estimation of these drugs in combined dosage forms.

  19. Efficacy and safety of the partial PPARγ agonist balaglitazone compared with pioglitazone and placebo: A phase III, randomised, parallel-group study in patients with type 2 diabetes on stable insulin therapy

    DEFF Research Database (Denmark)

    Henriksen, Kim; Byrjalsen, Inger; Qvist, Per

    2011-01-01

    Treatment of patients with full PPARγ agonists is associated with weight gain, heart failure, peripheral oedema and bone loss. However, the safety of partial PPARγ agonists has not been established in a clinical trial. The BALLET trial aimed to establish the glucose-lowering effects and safety...... parameters of the partial PPARγ agonist balaglitazone in diabetic patients on stable insulin therapy. 409 subjects from 3 countries with type 2 diabetes on stable insulin therapy were randomised to 26 weeks of double-blind treatment with once daily doses of 10 or 20mg balaglitazone, 45 mg pioglitazone...

  20. EFFECT OF PIOGLITAZONE ON HEPATIC ULTRA-STRUCTURE AND METABOLIC CHANGES INDUCED BY A HIGH SUCROSE DIET IN RATS

    Directory of Open Access Journals (Sweden)

    Mohamed D. Morsy

    2014-01-01

    Full Text Available Pioglitazone (Pio is a PPAR-γ agonist insulin sensitizer has anti-inflammatory activity. Our novel aspect was to investigate its hepatic anti-inflammatory activity at the level of ultra-structure and enzymatic changes in a high sucrose diet animal model. Forty male Sprague Dawley rats were divided into four equal groups: Control; control Pio; high sucrose diet; high sucrose diet Rio treated groups. Fourteen weeks later, serum glucose, insulin, lipogram, gamma glutamyle transferase, alanine transaminase, aspartate transaminase, alkaline phosphatase, fetuin-A and adiponectin levels were measured. Hepatic tissue homogenate levels of tumor necrosis factor-α, interleukin-6 and myeloperoxidase activity were determined. Microscopic and ultra-structure hepatic changes were conducted in all animal groups. Administration of Pio in HS+Pio group reduced significantly the hepatic inflammatory markers and the hepatic enzymes compared with HS group. Both light and electron microscopic examination revealed a great improvement of the hepatic tissue with Pio treatment. This study suggested that Pio treatment in obesity; in addition to insulin sensitizing activity; could protect the liver from the development of hepatic inflammation induced by a high sucrose diet not only at the enzymatic but also at ultra-structure levels.

  1. Safety profiling of pioglitazone and telmisartan combination by sub-chronic toxicity study in rat.

    Science.gov (United States)

    Sengupta, Pinaki; Das, Arindam; Ibrahim, Fuzianna; Mandal, Uttam Kumar; Chatterjee, Bappaditya; Mahmood, Syed; Das, Sreemoy Kanti; Kifayatullah, Muhammad

    2016-11-01

    It has been reported that the major cause of mortality in diabetes is cardiovascular diseases and contribution of hypertension is significant in this context. Pioglitazone, a thiazolidinedione class of therapeutic agent is used to treat type 2 diabetes mellitus. Telmisartan, an angiotensin receptor blocker antihypertensive has been reported to have beneficial effect if co-administered with pioglitazone for the management of diabetes complications. The present research work aims to evaluate the safety/toxicity profile of this combination in rat model. The investigation was carried out after co-administering the drugs to the rats for 28 days at three dose levels of 50, 100 and 150 mg/kg covering low to high dose ranges. Various hematological and biochemical parameters were studied in addition to the histopathology of the major organs in order to evaluate the toxicity profile of the combination. Absence of mortality and histopathological changes as well as unaltered hematological and biochemical parameters was observed. This preliminary investigation concludes that the combination of pioglitazone and telmisartan can primarily be stated as safe in animals, even at the dose level which is several folds higher than the intended human dose. Thus, this combination can be explored in future to develop a rational therapy regimen to treat hypertensive diabetic patients.

  2. 吡格列酮对2型糖尿病肾病患者骨桥蛋白和尿微量白蛋白的影响%Effects of pioglitazone on serum osteopontin and urinary microalbuminuria in type 2 diabetic patients with diabetic nephropathy

    Institute of Scientific and Technical Information of China (English)

    张筠; 王建平; 臧丽; 张世静

    2012-01-01

    Objective To investigate the effect of pioglitazone on serum OPN and UMA/Cr in type 2 diabetic patients with diabetic nephropathy. Methods Ninety type 2 diabetes patients were divided into two groups randomly according to UMA/Cr of Standards of Medical Care in Diabetes of 2009,diabetes mellitus (DM, UMA/Cr < 30 μg/mg, n = 30) and diabetic nephropathy ( DN,UMA/Cr: 30-299μg/mg,n = 60). Meanwhile, thirty healthy cases were selected for the Normal control (NC,n = 30). Then DN were randomly divided into two groups; placebo group (placebo combined with Insulin therapy, n = 30) and pioglitazone group (Pioglitazone combined with Insulin therapy, n = 30). In all of the objectives, levels of glucose, lipid, renal function, CRP, OPN and UMA/Cr were examined and analyzed. Results After 3-month treatment, compared with placebo group, the levels of UMA/ Cr [ (35.02 ±6.38) vs (86.30 ± 12.21 )p.g/mg, P<0.01], OPN [(394.24 ± 19.43) vs (457.00+ 15.21) ng/mL, P < 0.01 ] and HbAlc , TG, CRP in pioglitazone group were significanct decreased, the difference was significance. In the pioglitazone group the levels of A UMA/Cr (△: the difference between before and after treatment) were correlated positively with AOPN (r = 0.673 ,P = 0.000). Conclusions The level of OPN is significant increase in type 2 diabetic patients with diabetic nephropathy Pioglitazone can reduce level of UMA/Cr, may be achieve partly by reduce the level of serum OPN.%目的:探讨吡格列酮对2型糖尿病(T2DM)早期肾病患者血清骨桥蛋白(OPN)及尿微量白蛋白/尿肌酐比值(UMA/Cr)的影响.方法:90例T2DM患者按照2009年ADA糖尿病指南以UMA/Cr分为单纯糖尿病组(DM,UMA/Cr< 30 μg/mg)30例、糖尿病肾病组(DN,UMA/Cr:30 ~ 299 μg/mg)60例,同时选择30名体检正常者为正常对照组.再将DN组随机分为吡格列酮组30例(吡格列酮30 mg/d+胰岛素,n=30)和安慰剂组30例(安慰剂+胰岛素,n=30),随访治疗3个月.所有对象均测定血糖、血

  3. 吡格列酮对大鼠脑出血后脑组织细胞凋亡及自由基水平的影响%Effects of Pioglitazone on Cell Apoptosis and Free Radical Levels in Brain Tissue of Rats withIntracerebral Hemorrhage

    Institute of Scientific and Technical Information of China (English)

    韩宁; 吴丹红; 黄菲菲; 孙姬

    2012-01-01

    Aim: To investigate the protective effect of pioglitazone on intracerebral hemorrhage in rats and its possible mechanism. Methods: A total of 72 male SD rats were divided randomly into six groups. Intervention group 1 (n=12): Pioglitazone peroxisome proliferator-activated receptor gamma(PPAR7 activator) were gastrically administrated 6 h before modeling, and the original dosages were maintained after modeling. Intervention group 2 (n=12): Pioglitazone were gastrically administrated 6 h before modeling, and were withdrawn after modeling. Intervention group 3 (n=12): The drugs were not given before modeling, and were gastrically administrated after modeling. Model group 4 (n=12): The drags were not given before and after modeling. Sham operation group (n=12): The rats were performed with needling insertion without injection. Normal group (n=12) was set up. The dose of gastrically administrated pioglitazone was 15 mg·kg-1d-1. Rats in each group were sacrificed at 72 h after operation. Biochemical detection of the superoxide dismutase (SOD) and malondialdehyde (MDA) concentration of brain tissue were performed. The Western blot was used to determine the PPARy and caspase-3 protein expression in brain tissue. HE and TUNEL staining were used to observe the brain edema and apoptosis respectively. Results: PPARy activator pioglitazone could significantly reduce the extent of brain edema and inflammatory cell infiltration of the brain tissue in rats at 72 h after cerebral hemorrhage, as well as reduce the number of apoptotic cells in brain tissue, and enhance the SOD activity and increase the expression of PPARy, and caspase-3 protein in brain tissue, and inhibit the MDA levels. The effect of prophylactic administration of piogiitazone before cerebral hemorrhage was better than that of the treatment after hemorrhage. Conclusion: PPARy activator pioglitazone can relieve the hemorrhagic brain injury in the rat brain, and protect the brain, possibly by increasing the PPARy

  4. The effects of the PPAR-gamma gonist pioglitazone on plasma concentrations of circulating vasoactive factors in type II diabetes mellitus

    NARCIS (Netherlands)

    de Boer, R. A.; Martens, F. M. A. C.; Kuipers, I.; Boomsma, F.; Visseren, F. L. J.

    2010-01-01

    The use of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist pioglitazone, which is registered as an oral antidiabetic drug, has consistently been associated with a decrease in blood pressure (BP) of about 3-5 mm Hg. The present study evaluates the effects of pioglitazone tre

  5. Treatment of nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Juergen Siebler; Peter R Galle

    2006-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause for elevated liver enzymes in the developed nations. Beyond prevention programs which are of particular interest because of the increasing number of overweight children, treatment should be focussed on the most important risk factors, obesity and insulin resistance. As a consequence of elucidating the pathomechanisms of NAFLD, the number of potential therapeutic options increased. However, many studies investigating the therapeutic effect show shortcomings in at least one of the following points: lack of a serial liver biopsy, short term of treatment and limited number of included patients. The second generation insulin sensitizer pioglitazone and rosiglitazone show the most promising improvements in NAFLD, but weight gain and potential hepatotoxicity calls for attention. In conclusion,a general recommendation for the application of specific drugs cannot be given. Besides controlled clinical trials,weight reduction and physical activity to improve insulin sensitivity in obese patients should be the priority objective.

  6. Imaging of a glucose analog, calcium and NADH in neurons and astrocytes: dynamic responses to depolarization and sensitivity to pioglitazone.

    Science.gov (United States)

    Pancani, Tristano; Anderson, Katie L; Porter, Nada M; Thibault, Olivier

    2011-12-01

    Neuronal Ca(2+) dyshomeostasis associated with cognitive impairment and mediated by changes in several Ca(2+) sources has been seen in animal models of both aging and diabetes. In the periphery, dysregulation of intracellular Ca(2+) signals may contribute to the development of insulin resistance. In the brain, while it is well-established that type 2 diabetes mellitus is a risk factor for the development of dementia in the elderly, it is not clear whether Ca(2+) dysregulation might also affect insulin sensitivity and glucose utilization. Here we present a combination of imaging techniques testing the disappearance of the fluorescent glucose analog 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) as an indication of glycolytic activity in neurons and astrocytes. Our work shows that glucose utilization at rest is greater in neurons compared to astrocytes, and ceases upon activation in neurons with little change in astrocytes. Pretreatment of hippocampal cultures with pioglitazone, a drug used in the treatment of type 2 diabetes, significantly reduced glycolytic activity in neurons and enhanced it in astrocytes. This series of experiments, including Fura-2 and NADH imaging, provides results that are consistent with the idea that Ca(2+) levels may rapidly alter glycolytic activity, and that downstream events beyond Ca(2+) dysregulation with aging, may alter cellular metabolism in the brain.

  7. MitoNEET Is a Uniquely Folded 2Fe-2S Outer Mitochondrial Membrane Protein Stabilized By Pioglitazone

    Energy Technology Data Exchange (ETDEWEB)

    Paddock, M.L.; Wiley, S.E.; Axelrod, H.L.; Cohen, A.E.; Roy, M.; Abresch, E.C.; Capraro, D.; Murphy, A.N.; Nechushtai, R.; Dixon, J.E.; Jennings, P.A.; /UC, San Diego /SLAC, SSRL /Hebrew U.

    2007-10-19

    Iron-sulfur (Fe-S) proteins are key players in vital processes involving energy homeostasis and metabolism from the simplest to most complex organisms. We report a 1.5 Angstrom x-ray crystal structure of the first identified outer mitochondrial membrane Fe-S protein, mitoNEET. Two protomers intertwine to form a unique dimeric structure that constitutes a new fold to not only the {approx}650 reported Fe-S protein structures but also to all known proteins. We name this motif the NEET fold. The protomers form a two-domain structure: a {beta}-cap domain and a cluster-binding domain that coordinates two acid-labile 2Fe-2S clusters. Binding of pioglitazone, an insulin-sensitizing thiazolidinedione used in the treatment of type 2 diabetes, stabilizes the protein against 2Fe-2S cluster release. The biophysical properties of mitoNEET suggest that it may participate in a redox-sensitive signaling and/or in Fe-S cluster transfer.

  8. Lithium, phenserine, memantine and pioglitazone reverse memory deficit and restore phospho-GSK3β decreased in hippocampus in intracerebroventricular streptozotocin induced memory deficit model.

    Science.gov (United States)

    Ponce-Lopez, Teresa; Liy-Salmeron, Gustavo; Hong, Enrique; Meneses, Alfredo

    2011-12-02

    Intracerebroventricular (ICV) streptozotocin (STZ) treated rat has been described as a suitable model for sporadic Alzheimer's disease (AD). Central application of STZ has demonstrated behavioral and neurochemical features that resembled those found in human AD. Chronic treatments with antioxidants, acetylcholinesterase (AChE) inhibitors, or improving glucose utilization drugs have reported a beneficial effect in ICV STZ-treated rats. In the present study the post-training administration of a glycogen synthase kinase (GSK3) inhibitor, lithium; antidementia drugs: phenserine and memantine, and insulin sensitizer, pioglitazone on memory function of ICV STZ-rats was assessed. In these same animals the phosphorylated GSK3β (p-GSK3β) and total GSK3β levels were determined, and importantly GSK3β regulates the tau phosphorylation responsible for neurofibrillary tangle formation in AD. Wistar rats received ICV STZ application (3mg/kg twice) and 2 weeks later short- (STM) and long-term memories (LTM) were assessed in an autoshaping learning task. Animals were sacrificed immediately following the last autoshaping session, their brains removed and dissected. The enzymes were measured in the hippocampus and prefrontal cortex (PFC) by western blot. ICV STZ-treated rats showed a memory deficit and significantly decreased p-GSK3β levels, while total GSK3β did not change, in both the hippocampus and PFC. Memory impairment was reversed by lithium (100mg/kg), phenserine (1mg/kg), memantine (5mg/kg) and pioglitazone (30 mg/kg). The p-GSK3β levels were restored by lithium, phenserine and pioglitazone in the hippocampus, and restored by lithium in the PFC. Memantine produced no changes in p-GSK3β levels in neither the hippocampus nor PFC. Total GSK3β levels did not change with either drug. Altogether these results show the beneficial effects of drugs with different mechanisms of actions on memory impairment induced by ICV STZ, and restored p-GSK3β levels, a kinase key of

  9. A Multicenter, Prospective, Randomized, Double-blind Study to Evaluate the Safety and Efficacy of Saroglitazar 2 and 4 mg Compared to Pioglitazone 45 mg in Diabetic Dyslipidemia (PRESS V).

    Science.gov (United States)

    Pai, Vikas; Paneerselvam, A; Mukhopadhyay, Satinath; Bhansali, Anil; Kamath, Dinesh; Shankar, V; Gambhire, Dhiraj; Jani, Rajendrakumar H; Joshi, Shashank; Patel, Pankaj

    2014-01-01

    Dual PPARα/γ can improve both metabolic effects and minimized the side effects caused by either PPARα or PPARγ agonist. The PRESS V study was aimed to evaluate the safety, tolerability, and efficacy of saroglitazar 2 mg and 4 mg capsules (Lipaglyn™; Zydus Code: ZYH1) as compared to high dose pioglitazone in patients with diabetic dyslipidemia. In this 26-week double-blind, parallel arm, phase 3 study patients with hypertriglyceridemia with type 2 diabetes mellitus (BMI > 23 kg/m(2); hypertriglyceridemia: TG > 200 to 400 mg/dL; glycosylated hemoglobin [HbA1c] >7 to 9%) were enrolled from 14 sites in India. After 2 weeks of lifestyle modification, 122 patients were randomized double-blind to 24-week treatment with the study drugs (saroglitazar 2 mg or 4 mg or pioglitazone 45 mg once daily) in a 1:1:1 ratio. The primary end point was change in plasma triglyceride level at week 24. The secondary end points were change in lipid profile and fasting plasma glucose at week 24. Patients who received study medication and had undergone at least 1 postbaseline efficacy evaluation were included in the efficacy analysis. All randomized patients who received at least a single dose were included for safety evaluation. The efficacy analysis included 109 patients (n = 37 in saroglitazar 2 mg; n = 39 in saroglitazar 4 mg; n = 33 in pioglitazone). Saroglitazar 2 mg and 4 mg significantly reduced (P pioglitazone -15.5% (absolute change ± SD: -33.3 ± 162.41 mg/dL) at week 24. Saroglitazar 4 mg treatment also demonstrated marked decrease in low-density lipoprotein (5%), very-low-density lipoprotein (45.5%), total cholesterol (7.7%), and apolipoprotein-B (10.9%). Saroglitazar treatment was generally safe and well tolerated. No serious adverse events were reported in saroglitazar treatment arm and no persistent change in laboratory parameters. Saroglitazar appeared to be an effective and safe therapeutic option for improving hypertriglyceridemia in patients with type 2 diabetes

  10. Anti-pruritic activity of pioglitazone on serotonin-induced scratching in mice: possible involvement of PPAR-gamma receptor and nitric oxide.

    Science.gov (United States)

    Shafizadeh, Milad; Rajaba, Armin; Imran khan, Muhammad; Ostadhadi, Sattar; Rastegar, Hosein; Dehpour, Ahmadreza

    2014-12-05

    Pioglitazone is a member of peroxisome proliferator-activated receptor gamma (PPARγ) agonists, particularly used in management of type II diabetes. However it also has effects in some dermatological disorders. The current study was designed to investigate the effects of oral administration of pioglitazone and the association of nitric oxide, in serotonin-induced scratching in mice. In order to produce the scratching activity, serotonin (141 nm/site) was administered intradermally in the nape of the neck. Pioglitazone in concentrations of 10, 20, 40 and 80 mg/kg, was peroral administered (p.o) as a single dose, 4 h before the serotonin injection. PPAR-γ antagonist, GW9662 (2 mg/kg, i.p); a non-specific nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 1 mg/kg, i.p); or a nitric oxide precursor, L-arginine (100 mg/kg, i.p.); adminstrated 15 min before pioglitazone were analyzed for anti-scratching activity. Results obtained showed that pioglitazone (40 and 80 mg/kg, p.o) reduced the scratching in a dose-dependent manner. GW9662 inverted the anti-scratching effect of pioglitazone (80 mg/kg). Acute dose of L-NAME (1 mg/kg, i.p) also prevented the anti-scratching property of pioglitazone (80 mg/kg, p.o); although L-arginine was used in sub-effective dose (100 mg/kg, i.p), however it potentiated the anti-scratching behavior when co-injected with pioglitazone (20 mg/kg, p.o). The results indicate that acute pioglitazone has an anti-scratching effect on serotonin-induced scratching in mice. It is concluded that anti-scratching outcome of acute pioglitazone is initiated via activation of PPAR-γ receptor and to some extent by the NO pathway.

  11. Elimination of African onchocerciasis: modeling the impact of increasing the frequency of ivermectin mass treatment.

    Directory of Open Access Journals (Sweden)

    Luc E Coffeng

    Full Text Available The African Programme for Onchocerciasis Control (APOC is currently shifting its focus from morbidity control to elimination of infection. To enhance the likelihood of elimination and speed up its achievement, programs may consider to increase the frequency of ivermectin mass treatment from annual to 6-monthly or even higher. In a computer simulation study, we examined the potential impact of increasing the mass treatment frequency for different settings. With the ONCHOSIM model, we simulated 92,610 scenarios pertaining to different assumptions about transmission conditions, history of mass treatment, the future mass treatment strategy, and ivermectin efficacy. Simulation results were used to determine the minimum remaining program duration and number of treatment rounds required to achieve 99% probability of elimination. Doubling the frequency of treatment from yearly to 6-monthly or 3-monthly was predicted to reduce remaining program duration by about 40% or 60%, respectively. These reductions come at a cost of additional treatment rounds, especially in case of 3-monthly mass treatment. Also, aforementioned reductions are highly dependent on maintained coverage, and could be completely nullified if coverage of mass treatment were to fall in the future. In low coverage settings, increasing treatment coverage is almost just as effective as increasing treatment frequency. We conclude that 6-monthly mass treatment may only be worth the effort in situations where annual treatment is expected to take a long time to achieve elimination in spite of good treatment coverage, e.g. because of unfavorable transmission conditions or because mass treatment started recently.

  12. HPLC-DAD Method for the Pharmacokinetic Interaction Study of Atorvastatin with Pioglitazone and Cholestyramine in Wistar Rats.

    Science.gov (United States)

    Sharma, Ritesh N; Pancholi, Shyam S

    2014-01-01

    Carotid intima-media thickness is used as a surrogate marker for cardiovascular complications in diabetes mellitus. The combination of atorvastatin and pioglitazone was found to be effective in reducing the thickness of the carotid intima-media layer. The method of RP-HPLC coupled with a diode array detector (DAD) was developed for the pharmacokinetic interaction study of atorvastatin with pioglitazone and cholestyramine, respectively, in Wistar rats. Atorvastatin (ATR) and pioglitazone (PIO) were resolved on a C18 column with a mobile phase composed of 48% methanol, 19% acetonitrile, and 33% 10 mM ammonium formate (v/v/v; pH 3.5±0.3, by formic acid) and a 260 nm detection wavelength on the diode array detector. The method was validated according to international standards with good reproducibility and linear response; mean (r) 0.9987 and 0.9972 to ATR and PIO, respectively. The coefficients of variation of intra- and interassay precision ranged between 4.95-8.12 and 7.29-9.67, respectively. Pharmacokinetic parameters were determined in rats following an oral administration of atorvastatin in the presence and absence of pioglitazone and also with cholestyramine. Compared with the control given atorvastatin alone, the Cmax and AUC of atorvastatin were merely unchanged in rats with the co-administration of pioglitazone, while they decreased by nearly 21 and 15%, respectively, with the concurrent use of cholestyramine. There were no significant changes in Tmax and the plasma half-life (T1/2 ) of atorvastatin in both cases. The performed experiment demonstrated that the presented method was suitable for the estimation and pharmacokinetic interaction study of atorvastatin with pioglitazone and cholestyramine in Wistar rat plasma.

  13. Increasing Treatment Seeking Among At-Risk Service Members Returning from Warzones

    Science.gov (United States)

    2017-03-01

    1 Award Number: W81XWH-13-2-0032 TITLE: Increasing Treatment Seeking Among At- Risk Service Members Returning from Warzones PRINCIPAL...4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-13-2-0032 Increasing Treatment Seeking Among At- Risk Service Members Returning from Warzones 5b...include area code) Nothing listed 15 USAMRMC 2 Abstract Increasing Treatment Seeking Among At- Risk Service Members Returning from Warzones PI

  14. Cost-effectiveness analysis of sitagliptin and pioglitazone in poorly controlled type 2 diabetes mellitus patients with oral metformin%二甲双胍控制不佳的2型糖尿病患者联合应用磷酸西格列汀的成本-效果分析

    Institute of Scientific and Technical Information of China (English)

    梁菁菁; 邹大进

    2013-01-01

    Objective To compare cost-effectiveness and short-term clinical outcome of sitagliptin and pioglitazone in poorly controlled type 2 diabetes mellitus (T2DM) patients with oral metformin.Methods The clinical data of 152 T2DM patients were retrospectively analyzed.The efficacy and cost-effectiveness was compared between oral mefformin combined with sitagliptin and pioglitazone for the treatment of T2DM.Results Compared with baseline,the body weight of the patients treated with metformin plus pioglitazone was significantly increased (P<0.05),whereas it was significantly decreased in the patients with metformin plus sitagliptin (P<0.05).Fasting plasma glucose (FPG),glycosylated hemoglobin (HbA1c),total cholesterol (TC),triglyceride (TG),high-density lipoprotein cholesterol (HDL-C),and low-density lipoprotein cholesterol (LDL-C) were significantly reduced in all patients after treatment (P<0.05).The body weight of the patients with metformin plus sitagliptin was significantly lower than that of the patients treated with metformin plus pioglitazone after treatment (P<0.05).There were no significant differences in total effective rates (FPG and HbA1c control) or incidence rates of adverse effect between the two groups (all P>0.05).The total cost was 2 064.3 yuan in the pioglitazone group and 1 577.1 yuan in the sitagliptin group.Cost-effectiveness analysis showed that in the control of FPG the ratio of cost to effectiveness (C/E) was 25.0 and 21.0 in the pioglitazone group and sitagliptin group,respectively (△C△E was 65.0) ; C/E in the control of HbA1c was 22.9 and 18.9 in the two groups,respectively (△C△E was 72.7).Sensitivity test showed that the total cost was 1 930.5 yuan and 1 492.1 yuan in the pioglitazone group and sitagliptin group after adjustment; C/E in the control of FPG was 23.4 and 22.7 in the two groups (△C△E was58.5) ; C/E in the control of HbA1c was 21.5 and 17.9 (△C/△E was 65.4).Conclusion Additional use of sitagliptin in poorly

  15. Inhibitory effect of pioglitazone on the expression of the inflammatory cytokines after traumatic brain injury in rats%吡格列酮对大鼠创份性脑损伤后炎症因子抑制作用的研究

    Institute of Scientific and Technical Information of China (English)

    黄昭; 王思荣; 刘继云; 林材元

    2009-01-01

    Objective To observe the effects of peroxisome proliferator activated receptor-γ (PPAR-γ) and its activator pioglitazone on the expression of the inflammatory cytokines after traumatic brain injury (TBI) in rats and explore its mechanism. Methods Adult SD rats were randomized into normal control (n=10), sham-operated (n=10), TBI model (n=12) and pioglitazone treatment (n=12) groups. Impact brain injury was induced in the later two groups and 18 h after the injury, normal saline and pioglitazone at the daily dose of 20 mg/kg were given, respectively. The rats in the sham-operated group received identical treatment to the model group but without TBI. Seven days later, the brain tissue was collected and the cerebral water contents were measured. RT-PCR and Western blot were performed to detect the mRNA and protein expressions of PPAR-γ, regulated upon activation normal T cell expressed and secreted (RANTES) and macrophage migration inhibitory factor (MIF). Results Cerebral water content of the TBI model group was markedly increased as compared with that of the control and sham-operated groups (P<0.05). The expressions of PPAR-γ, RANTES and MIF significantly increased after TBI, and pioglitazone treatment resulted in further activation of PPAR-γ but markedly down-regulated RANTES and MIF expressions (P<0.05). Conclusion Pioglitazone offers protective effect against sustained brain edema and inflammation after TBI possibly by lowering the expressions of such inflammatory cytokines as RANTES and MIF in the brain tissue.%目的 探讨过氧化物酶体增殖物激活受体-γ(PPAR-γ)及其激活剂噻唑烷二酮类药物--吡格列酮对创伤性脑损伤(TBI)大鼠模型脑组织中正常T细胞活化后表达和分泌的调节蛋白(RANTES)、巨噬细胞移动抑制因子(MIF)表达的影响. 方法成年SD大鼠按照随机数字表法分为正常对照组(10只)、假手术组(10只)、TBI模型组(12只)及吡格列酮治疗组(12只).后两组采用改进

  16. Effects of Pioglitazone on Cardiovascular System in Type 2 Diabetes%吡格列酮对2型糖尿病患者心血管系统的影响

    Institute of Scientific and Technical Information of China (English)

    董璇

    2011-01-01

    糖尿病是最常见的慢性病之一.糖尿病亦被视为血管性疾患,因而防治心血管疾病成为糖尿病治疗的主要靶标.吡格列酮是一种噻唑烷二酮类药物,作用机制是通过活化靶组织中的过氧化物酶增殖物激活受体发挥作用.吡格列酮除了改善胰岛素抵抗和降低血糖外,还具有抑制平滑肌细胞增殖、保护血管内皮细胞、降压、抑制炎性细胞产生、降低血脂、抗氧化、抑制动脉血管硬化等多种保护作用.现就吡格列酮在2型糖尿病患者心血管系统中的作用进行综述.%Diabetes is the one of the most common chronic diseases,which is also regarded as vascular disease, thus preventing cardiovascular diseases is the main target of diabetes treatment.Pioglitazone is a thiazolidinediones drug,which plays a hypoglycemic role through acting on peroxisome proliferator-activated receptor.Recent studies have found that pioglitazone can inhibit vascular smooth muscle cell proliferation, lower blood pressure,regulate blood lilpids, inhibit inflammatory cell production, anti-oxidant, protect vascular endothelial cells, and inhibit atherosclerosis, playing an protective role on cardiovascular system.Here is to present a systematic review of some published literatures on the effectiveness of pioglitazone.

  17. Effect of pioglitazone on in-stent restenosis after coronary drug-eluting stent implantation: a meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Ming-duo Zhang

    Full Text Available In-stent restenosis (ISR remains a common life-threatening complication and some studies have shown that pioglitazone can reduce the incidence of ISR in patients with drug-eluting stents (DES implantation. We conducted a meta-analysis to assess the effect of pioglitazone in preventing ISR after DES implantation.Randomized controlled trials (RCTs investigating the effects of pioglitazone for ISR after DES implantation were identified by systematic searches of multiple online databases and manual searches of related reference lists of identified trials through May 2014. The primary endpoint was the rate of ISR. Secondary endpoints included minimum lumen diameter, percentage stenosis of stented vessels, late loss, in-stent neointimal volume, target vessel revascularization (TVR, target lesion revascularization, myocardial infarction, stent thrombosis and death.Five studies, comprising 255 pioglitazone-treated patients and 245 controls, were identified in the current meta-analysis. Pioglitazone did not significantly reduce the rate of ISR (P = 0.20 with low heterogeneity (I2 = 13.3%, P = 0.32. For the secondary outcomes, pioglitazone did not substantially affect the pooled estimates of these endpoints except late loss (P = 0.01 and TVR (P = 0.04.The limited evidence indicates that pioglitazone does not demonstrate markedly beneficial effect in patients subjected to coronary DES implantation. However, the results should be interpreted with care given the small sample size. Further large-scale RCTs are needed.

  18. 吡格列酮对2型糖尿病患者血清脂联素与胰岛素抵抗的影响%Effects of pioglitazone on serum adiponectin levels and insulin resistance in patients with type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    代芳; 王长江; 章秋; 贾敬华; 胡红琳; 何勇; 左春林

    2009-01-01

    Aim To discuss the effects of pioglitazone on serum adiponectin levels and insulin resistance in patients with type 2 diabetes mellitus.Methods Forty-five subjects with type 2 diabetes mellitus which were matched with age and gender were assigned to either pioglitazone group or placebo group according to randomized,double-blind method (22 and 23 subjects respectively).Comparison of serum adiponectin,free fatty acid levels at baseline and after 12 weeks,together the levels of blood glucose,blood pressure,blood lipids,height,weight,waist circumference,hip circumference,body mass index (BMI),waist-hip ratio (WHR) and insulin sensitivity index (ISI),islet β-cell function (HOMA-IR) were evaluated.Results Compared with placebo group,there was no significant difference between serum adiponectin and serum free fatty acid levels before treatment .After 12 weeks′treatment with pioglitazone,blood glucose and insulin resistance improved significantly(P0.05).结论 吡格列酮除改善血糖及胰岛素抵抗外,还可使血清脂联素水平升高,FFA水平降低,提示吡格列酮可能通过降低FFA、升高脂联素水平改善2型糖尿病患者胰岛素抵抗.

  19. Increasing spelling achievement: an analysis of treatment procedures utilizing an alternating treatments design.

    OpenAIRE

    Ollendick, T. H.; Matson, J L; Esveldt-Dawson, K; Shapiro, E S

    1980-01-01

    Two studies which examine the effectiveness of spelling remediation procedures are reported. In both studies, an alternating treatment design was employed. In the first study, positive practice overcorrection plus positive reinforcement was compared to positive practice alone and a no-remediation control condition. In the second study, positive practice plus positive reinforcement was compared to a traditional corrective procedure plus positive reinforcement and a traditional procedure when u...

  20. The effectiveness of liraglutide in nonalcoholic fatty liver disease patients with type 2 diabetes mellitus compared to sitagliptin and pioglitazone.

    Science.gov (United States)

    Ohki, Takamasa; Isogawa, Akihiro; Iwamoto, Masahiko; Ohsugi, Mitsuru; Yoshida, Haruhiko; Toda, Nobuo; Tagawa, Kazumi; Omata, Masao; Koike, Kazuhiko

    2012-01-01

    BACKGROUND. Liraglutide leading to improve not only glycaemic control but also liver inflammation in non-alcoholic fatty liver disease (NAFLD) patients. AIMS. The aim of this study is to elucidate the effectiveness of liraglutide in NAFLD patients with type 2 diabetes mellitus (T2DM) compared to sitagliptin and pioglitazone. METHODS. We retrospectively enrolled 82 Japanese NAFLD patients with T2DM and divided into three groups (liraglutide: N = 26, sitagliptin; N = 36, pioglitazone; N = 20). We compared the baseline characteristics, changes of laboratory data and body weight. RESULTS. At the end of follow-up, ALT, fast blood glucose, and HbA1c level significantly improved among the three groups. AST to platelet ratio significantly decreased in liraglutide group and pioglitazone group. The body weight significantly decreased in liraglutide group (81.8 kg to 78.0 kg, P pioglitazone group and did not change in sitagliptin group. Multivariate regression analysis indicated that administration of liraglutide as an independent factor of body weight reduction for more than 5% (OR 9.04; 95% CI 1.12-73.1, P = 0.04). CONCLUSIONS. Administration of liraglutide improved T2DM but also improvement of liver inflammation, alteration of liver fibrosis, and reduction of body weight.

  1. Revitalization of pioglitazone: the optimum agent to be combined with a sodium-glucose co-transporter-2 inhibitor.

    Science.gov (United States)

    DeFronzo, R A; Chilton, R; Norton, L; Clarke, G; Ryder, R E J; Abdul-Ghani, M

    2016-05-01

    The recently completed EMPA-REG study showed that empagliflozin significantly decreased the major adverse cardiac events (MACE) endpoint, which comprised cardiovascular death, non-fatal myocardial infarction (MI) and stroke, in patients with high-risk type 2 diabetes (T2DM), primarily through a reduction in cardiovascular death, without a significant decrease in either MI or stroke. In the PROactive study, pioglitazone decreased the MACE endpoint by a similar degree to that observed in the EMPA-REG study, through a marked reduction in both recurrent MI and stroke and a modest reduction in cardiovascular death. These observations suggest that pioglitazone might be an ideal agent to combine with empagliflozin to further reduce cardiovascular events in patients with high-risk diabetes as empagliflozin also promotes salt/water loss and would be expected to offset any fluid retention associated with pioglitazone therapy. In the present paper, we provide an overview of the potential benefits of combined pioglitazone/empagliflozin therapy to prevent cardiovascular events in patients with T2DM.

  2. Liquid Chromatographic Determination of Pioglitazone in Pharmaceuticals, Serum and Urine Samples

    Directory of Open Access Journals (Sweden)

    Shahnaz Perveen

    2011-12-01

    Full Text Available A rapid and reliable analytical method based on high-performance liquid chromatography (HPLC with UV detection (221nm has been developed for the determination of the anti-hyperglycemic agent Pioglitazone in pharmaceutical formulations and biological fluids (serum and urine after clean-up with solid-phase extraction. Chromatographic separation was achieved with a Chromolith® Performance RP-18e (100×4.6mm column using mobile phase composition of acetonitrile: mixed phosphate buffer (pH 2.5; 10mM (30:70, v/v with a flow rate of 2.0mL/min. The total run time was 2 min. under optimized conditions. The calibration curve was found to be linear in the range of 1-10 µg mL-1 with regression coefficient of 0.9996, and the lower limit of detection 72 ng/20µL injection. The method has been validated for the system suitability, linearity, precision and accuracy, limits of detection, specificity, stability and robustness. The %recovery of Pioglitazone in pharmaceutical formulations was found to be 104.7%. The assay has been applied successfully to the pharmaceutical Tablet samples and biological fluids (serum and urine of healthy volunteers.

  3. Pioglitazone--do we really need it to manage type 2 diabetes?

    Science.gov (United States)

    Sinha, Binayak; Ghosal, Samit

    2013-01-01

    Over the last few years a number of important drugs like rofecoxib, rosiglitazone, gatifloxacin (in diabetics) have lost their position in disease management. The newest controversy revolves around Pioglitazone, a thiozolidindione, which improves insulin sensitivity and is reputed to have cardioprotective actions, but is riddled with several controversies related to weight gain, distal fractures of long bones, recent reports of bladder cancer and others. There are now new groups of drugs, which have been introduced with stringent FDA approval. These include DPP-4 inhibitors, GLP-1 analogues and bromocriptine (old wine in a new bottle). Early in 2013 we are also looking at the launch of another new agent - SGLT-2 inhibitors. These newer agents are associated with not only a significant glucose lowering effect but also positive extra-glycaemic benefits principally in the areas of hypoglycaemia and weight gain. This raises a very important question - do we really need such a controversial agent when such a plethora of agents are available to us with possibly better metabolic profile than pioglitazone? This review addresses this highly contentious area dissecting the pros and cons as we see it.

  4. A Validated Adsorptive Stripping Voltammetric Determination of Antidiabetic Agent Pioglitazone HCl in Tablets and Biological Fluids

    Science.gov (United States)

    Al-Arfaj, Nawal Ahmad; Al-Abdulkareem, Eman Abdullah; Aly, Fatma Ahmad

    2008-01-01

    Square-wave adsorptive cathodic stripping voltammetry was used to determine pioglitazone HCl in Britton Robinson buffer of pH5. The adsorptive cathodic peak was observed at -1.5 V vs. Ag/AgCl. The peak response was characterized with respect to pH, supporting electrolyte, frequency, scan increment, pulse-amplitude, accumulation potential and pre-concentration time. Under optimal conditions, the peak current is proportional to the concentration of pioglitazone HCl, and a linear calibration graphs were obtained within the concentration levels of 10-8 and 10-4 M following different accumulation time periods (0-300 s). The obtained results were analyzed and the statistical parameters were calculated. The detection limit is 8.08 × 10-9 M (3.17 ng ml-1) using 300 s pre-concentration time, whereas the quantitative limit is 2.45 × 10-8 M (9.63 ng ml-1). The proposed method was applied to assay the drug in pharmaceutical formulations and biological fluids. The pharmacokinetic parameters of drug in human plasma were estimated as: Cmax=785.8 ng ml-1, tmax=1.5 h, Ke=0.125 h-1 and t1/2=8 h which are favorably compared with those reported in literature. PMID:23675103

  5. Effect of pioglitazone on serum adiponectin in patients with type 2 diabetic nephropathy%吡格列酮对2型糖尿病肾病血清脂联素水平的影响

    Institute of Scientific and Technical Information of China (English)

    陈小盼; 郑海龙; 朱洪; 宋钦华; 孙胜花

    2012-01-01

    OBJECTIVE To observe the change of pioglitazone on serum adiponeclin in patients with type 2 diabetic nephropa-thy. METHODS We chose 52 patients with type 2 diabetic nephropathy and divided them into two groups: diabetic nephropa-thy control group (DN group, n=29) and pioglitazone treatment group (pioglitazone group, n=23). All patients were treated with oral hypoglycemic agents or insulin to control blood sugar level. After blood sugar level remained stable for one week, the DN group continued to maintain the original treatment, and the pioglitazone group was additional oral pioglitazone tablet for 8 weeks (30mg/day). Fasting plasma glucose (FPG), glycosylated hemoglobin (HbAlc), 24 hour urinary albumin quantitative (24h UA), high-sensitivity C-reactive protein (hs-CRP) and adiponectin levels were measured before and after treatment in each group. RESULTS ①There was no significant difference in FPG, HbAlc, 24h UA, hs-CRP and adiponectin level between the DN group and the pioglitazone group before treatment (P> 0.05). ②Although there was no significant change in 24h UA, hs-CRP and adiponectin level before and after treatment in the DN group, all of them significantly decreased in the pioglitazone goup after treatment with pioglitazone for 8 weeks (P < 0.05). CONCLUSION Thiazolidinediones can decrease adiponectin level, alleviate damage on kidney and reduce urinary albumin filtration in the patients with type 2 diabetic nephropathy.%目的 观察噻唑烷二酮衍生物吡格列酮对2型糖尿病肾病患者血清脂联素水平的影响,并探讨其临床意义.方法 临床选择研究2型糖尿病肾病52例,分为糖尿病肾病对照组(29例)和吡格列酮治疗组(23例).所有患者均给予口服降糖药或胰岛素控制血糖常规治疗,待血糖稳定1周后,对照组继续维持原治疗,吡格列酮治疗组加用吡格列酮片口服8周(30 mg/日).各组治疗前后均测定空腹血糖(FPG)、糖化血红蛋白(HbA1c)、24 h

  6. Telomere length as a predictor of response to Pioglitazone in patients with unremitted depression: a preliminary study

    Science.gov (United States)

    Rasgon, N; Lin, K W; Lin, J; Epel, E; Blackburn, E

    2016-01-01

    We studied peripheral leukocyte telomere length (LTL) as a predictor of antidepressant response to PPAR-γ agonist in patients with unremitted depression. In addition we examined correlation between LTL and the insulin resistance (IR) status in these subjects. Forty-two medically stable men and women ages 23–71 with non-remitted depression participated in double-blind placebo-controlled add-on of Pioglitazone to treatment-as-usual. Oral glucose tolerance tests were administered at baseline and at 12 weeks. Diagnostic evaluation of psychiatric disorders was performed at baseline and mood severity was followed weekly throughout the duration of the trial. At baseline, no differences in LTL were detected by depression severity, duration or chronicity. LTL was also not significantly different between insulin-resistant and insulin-sensitive subjects at baseline. Subjects with longer telomeres exhibited greater declines in depression severity in the active arm, but not in a placebo arm, P=0.005, r=−0.63, 95% confidence interval (95% CI)=(−0.84,−0.21). In addition, LTL predicted improvement in insulin sensitivity in the group overall and did not differ between intervention arms, P=0.036, r=−0.44, 95% CI=(−0.74,0.02) for the active arm, and P=0.026, r=−0.50, 95% CI=(−0.78,−0.03) for the placebo arm. LTL may emerge as a viable predictor of antidepressant response. An association between insulin sensitization and LTL regardless of the baseline IR status points to potential role of LTL as a non-specific moderator of metabolic improvement in these patients. PMID:26731446

  7. Stress-induced increases in brainstem amino acid levels are prevented by chronic sodium hydrosulfide treatment.

    Science.gov (United States)

    Warenycia, M W; Kombian, S B; Reiffenstein, R J

    1990-01-01

    Neurotransmitter amino acid levels were measured in select brain regions of rats and mice after chronic treatment with sublethal doses of sodium hydrosulfide (NaHS). Brainstem aspartate, glutamate, glutamine, taurine and GABA levels increased in chronically but not acutely saline-treated rats. These increases may have been due to stress from frequent handling, and were prevented by chronic NaHS treatment (7.5 mg/kg ip every 8 hr for 3 consecutive days). In contrast, aspartate, glutamate and glutamine increased in female but not in male ICR mouse brainstems after once daily treatment with 7.0 mg/kg NaHS for 5 consecutive days. These effects of NaHS may indicate chronic low level H2S neurotoxicity. Differences between chronic and acute treatments, female and male responses, and treatment paradigms may complicate interpretations of such toxicity studies.

  8. No Increased Risk of Cancer after Coal Tar Treatment in Patients with Psoriasis or Eczema

    NARCIS (Netherlands)

    Roelofzen, Judith H. J.; Aben, Katja K. H.; Oldenhof, Ursula T. H.; Coenraads, Pieter-Jan; Alkemade, Hans A.; van de Kerkhof, Peter C. M.; van der Valk, Pieter G. M.; Kiemeney, Lambertus A. L. M.

    Coal tar is an effective treatment for psoriasis and eczema, but it contains several carcinogenic compounds. Occupational and animal studies have shown an increased risk of cancer after exposure to coal tar. Many dermatologists have abandoned this treatment for safety reasons, although the risk of

  9. Studies on linearty and assay using RP-HPLC and UV-visible spectroscopy for the drugs oxcarbazepine and pioglitazone before and after expiry period

    National Research Council Canada - National Science Library

    Suganya, S; Bright, A; Devi, T.S. Renuga

    2012-01-01

    .... In the present investigation RP-HPLC and UV-Visible spectroscopic methods are employed for estimation of drugs oxcarbazepine and pioglitazone in tablet dosage form before expiry period and 10-12 months after its expiry...

  10. HPLC method development, validation and its application to investigate in vitro effect of pioglitazone on the availability of H1 receptor antagonists

    Directory of Open Access Journals (Sweden)

    Agha Zeeshan Mirza

    2017-02-01

    Full Text Available The method has been developed and validated for the simultaneous determination of pioglitazone and H1-receptor antagonists (fexofenadine, cetirizine and levocetirizine in formulations and human serum. Utilizing HPLC techniques, an assay was designed to determine the in vitro effects of pioglitazone on H1-receptor antagonists. Obtained results were verified using the UV spectrophotometric technique. First-derivative values versus concentrations were used to plot calibration curves of these drugs and were found to similar with the HPLC data. The availability of pioglitazone remained unchanged in absence or presence of fexofenadine, cetirizine and levocetirizine. This in vitro analysis confirms the harmless co-administration of pioglitazone and H1-receptor antagonists, and can serve as the foundation for designing further in vivo studies.

  11. Targeting renal glucose reabsorption for the treatment of type 2 diabetes mellitus using the SGLT2 inhibitor dapagliflozin.

    Science.gov (United States)

    Jabbour, Serge A; Whaley, Jean M; Tirmenstein, Mark; Poucher, Simon M; Reilly, Timothy P; Boulton, David W; Saye, Joanne; List, James F; Parikh, Shamik

    2012-07-01

    Sodium-glucose co-transporter 2 (SGLT2) plays a key role in glucose homeostasis as the key transporter responsible for most renal glucose reabsorption in the proximal tubules of the kidney. Dapagliflozin is a potent, selective, and reversible inhibitor of SGLT2 that lowers blood glucose levels in an insulin-independent fashion. This novel agent has been studied extensively in patients with type 2 diabetes mellitus (T2DM). In these clinical trials, dapagliflozin significantly decreased glycated hemoglobin and fasting plasma glucose levels when administered alone or as add-on treatment in patients who were already receiving metformin, a sulfonylurea (glimepiride), pioglitazone, or insulin. Moreover, dapagliflozin decreased body weight when taken as monotherapy or in combination with metformin, a sulfonylurea, or insulin, and mitigated weight gain in patients receiving pioglitazone. Consistent with preclinical toxicology studies, dapagliflozin has a manageable adverse event profile that is largely predictable from its mechanism of action. While there are no clinically significant negative effects on renal function or electrolytes, dapagliflozin treatment is associated with increased frequencies of urinary tract infections and vulvovaginitis/balanitis. With a mechanism of action that is distinct from and complementary to that of existing antihyperglycemic therapies, dapagliflozin is an effective antihyperglycemic agent that is well tolerated and may enhance weight loss. As such, dapagliflozin promises to become an important adjunctive therapy for comprehensive treatment of T2DM.

  12. Combined ultrasonication and thermal pre-treatment of sewage sludge for increasing methane production.

    Science.gov (United States)

    Trzcinski, Antoine Prandota; Tian, Xinbo; Wang, Chong; Lin, Li Leonard; Ng, Wun Jern

    2015-01-01

    This article focuses on the combination of ultrasonic and thermal treatment of sewage sludge (SS). The combination involved ultrasonicating a fraction of the sludge and thermal treatment at various temperatures and this resulted in solubilization of proteins and carbohydrates, and so contributing to increased COD solubilization. During the treatment, SCOD, soluble proteins and carbohydrates increased from 760 mg L(-1) to 10,200 mg L(-1), 110 mg L(-1) to 2,900 mg L(-1) and 60 mg L(-1) to 630 mg L(-1), respectively. It was found ultrasonication of only a fraction of the sludge (>20%) followed by thermal treatment led to significant improvement compared to thermal and ULS treatments applied on their own. At 65°C, the kinetic of solubilization was improved and the hyper-thermophilic treatment time could be reduced to a few hours when ultrasonication was used first. A linear correlation (R(2) = 95%) was found between the SCOD obtained after ultrasonication pre-treatment and anaerobic biodegradability. The combined treatment resulted in 20% increase in biogas production during the anaerobic digestion of the pre-treated sludge.

  13. Appropriate insulin initiation dosage for insulin-naive type 2 diabetes outpatients receiving insulin monotherapy or in combination with metformin and/or pioglitazone

    Institute of Scientific and Technical Information of China (English)

    LIAO Lin; YANG Ming; QIU Lu-lu; MOU Ya-ru; ZHAO Jia-jun; DONG Jian-jun

    2010-01-01

    Background Few studies have given suggestions on appropriate initiation insulin dosage when combined with oral antidiabetic drugs (OADs). This research was to investigate appropriate initiation insulin doses for insulin-naive type 2diabetes patients with different combinations and the relationship between insulin dosage and relevant factors.Methods This was a randomized, open-label, treat to target study. The target was 20% decrease of both fasting plasma glucose (FPG) and 2 hours post-breakfast blood glucose (P2hBG). One hundred and forty-seven insulin-naive Chinese patients recruited were randomiy assigned to 3 groups: group A, patients received insulin monotherapy; group B, received insulin plus metformin (0.5 g, tid) and group C, received insulin plus metformin (0.5 g, tid) and pioglitazone (15 mg, qd).Results Both the time of getting 20% reduction of FPG and P2hBG showed significant differences among the three groups. The time was shortest in Group C. The insulin doses needed to achieve glucose reduction of 20% in three treatment groups were (0.40±0.04) U·kg-1·d-1 for Group A, (0.37±0.04) U·kg-1·d-1 for Group B, and (0.35±0.03) U·kg-1·d-1 for Group C, respectively. Multiple linear stepwise regression analysis showed that insulin doses correlated with body weight, FPG, diabetes duration, age and history of sulfonylurea treatment. The standardized regression coefficients were 0.871, 0.322, 0.089, 0.067 and 0.063 (with all P <0.05).Conclusions To achieve blood glucose's reduction of 20% within safety context, initial insulin doses were recommended as the following: 0.40 U·kg-1·d-1 for insulin mono-therapy, 0.37 U·kg-1·d-1 for insulin plus metformin treatment, and 0.35 U·kg-1.d-1 for insulin plus metformin and pioglitazone treatment in Chinese type 2 diabetes outpatients. Body weight is found the most closely related factor to the insulin dosage.

  14. Enzymatic Pre-Treatment Increases the Protein Bioaccessibility and Extractability in Dulse (Palmaria palmata

    Directory of Open Access Journals (Sweden)

    Hanne K. Mæhre

    2016-10-01

    Full Text Available Several common protein extraction protocols have been applied on seaweeds, but extraction yields have been limited. The aims of this study were to further develop and optimize existing extraction protocols and to examine the effect of enzymatic pre-treatment on bioaccessibility and extractability of seaweed proteins. Enzymatic pre-treatment of seaweed samples resulted in a three-fold increase in amino acids available for extraction. Combining enzymatic pre-treatment with alkaline extraction resulted in a 1.6-fold increase in the protein extraction yield compared to a standard alkaline extraction protocol. A simulated in vitro gastrointestinal digestion model showed that enzymatic pre-treatment of seaweed increased the amount of amino acids available for intestinal absorption 3.2-fold. In conclusion, enzymatic pre-treatment of seaweeds is effective for increasing the amount of amino acids available for utilization and may thus be an effective means for increasing the utilization potential of seaweed proteins. However, both the enzymatic pre-treatment protocol and the protein extraction protocol need further optimization in order to obtain optimal cost-benefit and results from the in vitro gastrointestinal digestion model need to be confirmed in clinical models.

  15. Generalized intense pruritus during canagliflozin treatment: Is it an adverse drug reaction?

    Science.gov (United States)

    Vasapollo, Piero; Cione, Erika; Luciani, Filippo; Gallelli, Luca

    2016-04-05

    Selective agents able to locate and identify unique targets represent a crucial aspect of modern pharmacology. The exclusive location of sodium-glucose co-transporter-2 (SGLUT2) on kidneys prompt companies to develop SGLT2 inhibitors that today are the latest class of drugs for diabetes treatment. In particular, canagliflozin blocks the re-absorption of glucose in the kidney lowering blood glucose levels by increasing glucose excretion. We report a 61-year old woman who developed an intense and severe pruritus during the treatment with canagliflozin. Clinical and laboratory findings excluded the presence of systemic or skin diseases able to induce pruritus. The discontinuation of canagliflozin and the treatment with pioglitazone/metformin fixed combination induced a remission of pruritus. This case emphasizes the need to consider pruritus as a differential diagnosis during the treatment with canagliflozin.

  16. Comparison of the efficacy of cardamom (Elettaria cardamomum with pioglitazone on dexamethasone-induced hepatic steatosis, dyslipidemia, and hyperglycemia in albino rats

    Directory of Open Access Journals (Sweden)

    G M Nitasha Bhat

    2015-01-01

    Full Text Available To evaluate the efficacy of cardamom with pioglitazone on dexamethasone-induced hepatic steatosis, dyslipidemia, and hyperglycemia in albino rats. There were four groups of 6 rats each. First group received dexamethasone alone in a dose of 8 mg/kg intraperitoneally for 6 days to induce metabolic changes and considered as dexamethasone control. Second group received cardamom suspension 1 g/kg/10 mL of 2% gum acacia orally 6 days before dexamethasone and 6 days during dexamethasone administration. Third group received pioglitazone 45 mg/kg orally 6 days before dexamethasone and 6 days during dexamethasone administration. Fourth group did not receive any medication and was considered as normal control. Fasting blood sugar, lipid profile, blood sugar 2 h after glucose load, liver weight, liver volume were recorded, and histopathological analysis was done. The effects of cardamom were compared with that of pioglitazone. Dexamethasone caused hepatomegaly, dyslipidemia and hyperglycemia. Both pioglitazone and cardamom significantly reduced hepatomegaly, dyslipidemia, and hyperglycemia (P < 0.01. Reduction of blood sugar levels after glucose load was significant with pioglitazone in comparison to cardamom (P < 0.01. Cardamom has comparable efficacy to pioglitazone in preventing dexamethasone-induced hepatomegaly, dyslipidemia, and fasting hyperglycemia.

  17. Long-term effects of pioglitazone on first attack of ischemic cerebrovascular disease in older people with type 2 diabetes: A case-control study in Taiwan.

    Science.gov (United States)

    Lai, Shih-Wei; Lin, Hsien-Feng; Lin, Cheng-Li; Liao, Kuan-Fu

    2016-08-01

    Long-term studies demonstrating the effect of pioglitazone use on primary prevention of ischemic cerebrovascular disease in older people with type 2 diabetes mellitus are lacking. This study investigated the relationship between pioglitazone use and first attack of ischemic cerebrovascular disease in Taiwan.We conducted a case-control study using the database of the Taiwan National Health Insurance Program. There were 2359 type 2 diabetic subjects aged ≥65 years with newly diagnosed ischemic cerebrovascular disease from 2005 to 2011 as the case group and 4592 sex- and age-matched, randomly selected type 2 diabetic subjects aged ≥65 years without ischemic cerebrovascular disease as the control group. The odds ratio (OR) with 95% confidence interval (CI) of ischemic cerebrovascular disease associated with pioglitazone use was measured by the multivariable unconditional logistic regression model.After adjustment for confounding factors, the multivariable logistic regression analysis disclosed that the adjusted ORs of first attack of ischemic cerebrovascular disease associated with cumulative duration of using pioglitazone were 3.34 for pioglitazone use does not have a protective effect on primary prevention for ischemic cerebrovascular disease among older people with type 2 diabetes mellitus during the first 3 years of use. Whether using pioglitazone for >3 years would have primary prevention for ischemic cerebrovascular disease needs a long-term research to prove.

  18. HPV16 and increased risk of recurrence after treatment for CIN.

    Science.gov (United States)

    Gök, Murat; Coupé, Veerle M H; Berkhof, Johannes; Verheijen, René H M; Helmerhorst, Theo J M; Hogewoning, Cornelis J A; Snijders, Peter J F; Meijer, Chris J L M

    2007-02-01

    Addition of high-risk human papillomavirus (hrHPV) testing to post-treatment monitoring policies of women treated for high-grade cervical intraepithelial neoplasia (CIN) may improve the effectiveness of detecting recurrent/residual disease. Recent studies have shown that HPV type 16 confers an increased risk of high-grade CIN and cervical cancer. This study aimed to find out whether the post-treatment CIN3 rate is increased in HPV16-positive women treated for CIN3. We included 229 hrHPV-positive women treated for CIN3. HPV typing was performed by GP5+/6+-PCR followed by reverse line blotting on a cervical scrape taken before treatment. HPV typing data were related to the occurrence of post-treatment CIN3 within a median follow-up time of 20.1 months (range 3-85.4 months) following treatment. Twenty nine of the 151 (19%) HPV16-positive women versus 6 of the 78 (8%) women with other hrHPV types had recurrent/residual CIN3. Post-treatment CIN3 rate was significantly increased in women with HPV16 compared to those harboring other hrHPV types (p=0.03). None of the other hrHPV types were associated with higher post-treatment CIN3 rates. Women treated for HPV16 containing CIN3 should be monitored more intensively because of their increased risk of post-treatment CIN3. Thus, the HPV genotype should be considered in post-treatment monitoring policies.

  19. Characterization of pioglitazone cyclodextrin complexes: Molecular modeling to in vivo evaluation

    Science.gov (United States)

    Bramhane, Dinesh M.; Kulkarni, Preethi A.; Martis, Elvis A. F.; Pissurlenkar, Raghuvir R. S.; Coutinho, Evans C.; Nagarsenker, Mangal S.

    2016-01-01

    Aims: The objective of present study was to study the influence of different β-cyclodextrin derivatives and different methods of complexation on aqueous solubility and consequent translation in in vivo performance of Pioglitazone (PE). Material and Methods: Three cyclodextrins: β-cyclodextrin (BCD), hydroxypropyl-β-cyclodextrin (HPBCD) and Sulfobutylether-7-β-cyclodextrin (SBEBCD) were employed in preparation of 1:1 Pioglitazone complexes by three methods viz. co-grinding, kneading and co-evaporation. Complexation was confirmed by phase solubility, proton NMR, Fourier Transform Infrared spectroscopy, Differential Scanning Calorimetry (DSC) and X-Ray diffraction (XRD). Mode of complexation was investigated by molecular dynamic studies. Pharmacodynamic study of blood glucose lowering activity of PE complexes was performed in Alloxan induced diabetic rat model. Results: Aqueous solubility of PE was significantly improved in presence of cyclodextrin. Apparent solubility constants were observed to be 254.33 M–1 for BCD-PE, 737.48 M–1 for HPBCD-PE and 5959.06 M–1 for SBEBCD-PE. The in silico predictions of mode of inclusion were in close agreement with the experimental proton NMR observation. DSC and XRD demonstrated complete amorphization of crystalline PE upon inclusion. All complexes exhibited >95% dissolution within 10 min compared to drug powder that showed <40% at the same time. Marked lowering of blood glucose was recorded for all complexes. Conclusion: Complexation of PE with different BCD significantly influenced its aqueous solubility, improved in vitro dissolution and consequently translated into enhanced pharmacodynamic activity in rats PMID:27134470

  20. Characterization of pioglitazone cyclodextrin complexes: Molecular modeling to in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Dinesh M Bramhane

    2016-01-01

    Full Text Available Aims: The objective of present study was to study the influence of different β-cyclodextrin derivatives and different methods of complexation on aqueous solubility and consequent translation in in vivo performance of Pioglitazone (PE. Material and Methods: Three cyclodextrins: β-cyclodextrin (BCD, hydroxypropyl-β-cyclodextrin (HPBCD and Sulfobutylether-7-β-cyclodextrin (SBEBCD were employed in preparation of 1:1 Pioglitazone complexes by three methods viz. co-grinding, kneading and co-evaporation. Complexation was confirmed by phase solubility, proton NMR, Fourier Transform Infrared spectroscopy, Differential Scanning Calorimetry (DSC and X-Ray diffraction (XRD. Mode of complexation was investigated by molecular dynamic studies. Pharmacodynamic study of blood glucose lowering activity of PE complexes was performed in Alloxan induced diabetic rat model. Results: Aqueous solubility of PE was significantly improved in presence of cyclodextrin. Apparent solubility constants were observed to be 254.33 M–1 for BCD-PE, 737.48 M–1 for HPBCD-PE and 5959.06 M–1 for SBEBCD-PE. The in silico predictions of mode of inclusion were in close agreement with the experimental proton NMR observation. DSC and XRD demonstrated complete amorphization of crystalline PE upon inclusion. All complexes exhibited >95% dissolution within 10 min compared to drug powder that showed <40% at the same time. Marked lowering of blood glucose was recorded for all complexes. Conclusion: Complexation of PE with different BCD significantly influenced its aqueous solubility, improved in vitro dissolution and consequently translated into enhanced pharmacodynamic activity in rats

  1. Increased Mental Health Treatment Financing, Community-Based Organization's Treatment Programs, and Latino-White Children's Financing Disparities.

    Science.gov (United States)

    Snowden, Lonnie R; Wallace, Neal; Cordell, Kate; Graaf, Genevieve

    2017-09-01

    Latino child populations are large and growing, and they present considerable unmet need for mental health treatment. Poverty, lack of health insurance, limited English proficiency, stigma, undocumented status, and inhospitable programming are among many factors that contribute to Latino-White mental health treatment disparities. Lower treatment expenditures serve as an important marker of Latino children's low rates of mental health treatment and limited participation once enrolled in services. We investigated whether total Latino-White expenditure disparities declined when autonomous, county-level mental health plans receive funds free of customary cost-sharing charges, especially when they capitalized on cultural and language-sensitive mental health treatment programs as vehicles to receive and spend treatment funds. Using Whites as benchmark, we considered expenditure pattern disparities favoring Whites over Latinos and, in a smaller number of counties, Latinos over Whites. Using segmented regression for interrupted time series on county level treatment systems observed over 64 quarters, we analyzed Medi-Cal paid claims for per-user total expenditures for mental health services delivered to children and youth (under 18 years of age) during a study period covering July 1, 1991 through June 30, 2007. Settlement-mandated Medicaid's Early Periodic Screening, Diagnosis and Treatment (EPSDT) expenditure increases began in the third quarter of 1995. Terms were introduced to assess immediate and long term inequality reduction as well as the role of culture and language-sensitive community-based programs. Settlement-mandated increased EPSDT treatment funding was associated with more spending on Whites relative to Latinos unless plans arranged for cultural and language-sensitive mental health treatment programs. However, having programs served more to prevent expenditure disparities from growing than to reduce disparities. EPSDT expanded funding increased proportional

  2. Increased Oil Recovery from Mature Oil Fields Using Gelled Polymer Treatments

    Energy Technology Data Exchange (ETDEWEB)

    Willhite, G.P.; Green, D.W.; McCool, S.

    2001-03-28

    Gelled polymer treatments were applied to oil reservoirs to increase oil production and to reduce water production by altering the fluid movement within the reservoir. This report is aimed at reducing barriers to the widespread use of these treatments by developing methods to predict gel behavior during placement in matrix rock and fractures, determining the persistence of permeability reduction after gel placement, and by developing methods to design production well treatments to control water production. Procedures were developed to determine the weight-average molecular weight and average size of polyacrylamide samples in aqueous solutions. Sample preparation techniques were key to achieving reproducible results.

  3. Patient education in groups increases knowledge of osteoporosis and adherence to treatment

    DEFF Research Database (Denmark)

    Nielsen, Dorthe; Ryg, Jesper; Nielsen, Winnie

    2010-01-01

    OBJECTIVE: Non-adherence to pharmacological treatment in osteoporosis is a well-recognized problem. We hypothesized that a group-based educational programme would increase patients' knowledge and level of adherence with medical treatment. METHODS: A total of 300 patients (32 men aged 65 ± 9 years...... empowerment. Patients' knowledge about osteoporosis and adherence to treatment was assessed with self-completed questionnaires at baseline and after 3, 12, and 24 months. RESULTS: There were no significant differences at baseline between the two groups with respect to knowledge score or level of adherence...

  4. Co-treatment of Salinomycin Sensitizes AZD5363-treated Cancer Cells Through Increased Apoptosis.

    Science.gov (United States)

    Choi, Ae-Ran; Jung, Myung-Ji; Kim, Ju-Hwa; Yoon, Sungpil

    2015-09-01

    AZD5363, an inhibitor of protein kinase B (AKT), is currently in clinical trials assessing the potential of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. The purpose of the present study was to identify conditions that increase the sensitivity of cancer cells to AZD5363. Microscopic examination revealed that treatment of cancer cells with a low concentration of salinomycin reduced cellular growth of AZD5363-treated breast cancer cells. Furthermore, fluorescence-activated cell sorting (FACS) analysis, Hoechst staining, and annexin V staining revealed that co-treatment with salinomycin sensitizes AZD5363-treated cancer cells via increased apoptosis with S-phase arrest. These results suggest that salinomycin can be applied to increase treatment efficacy for AZD5363-treated cancer cells. Our findings may contribute to improving the efficacy of the development of AZD5363-based sensitization therapies for patients with cancer.

  5. Increased Drinking in a Trial of Treatments for Marijuana Dependence: Substance Substitution?

    OpenAIRE

    Kadden, Ronald M.; Litt, Mark D.; Kabela-Cormier, Elise; Petry, Nancy M.

    2009-01-01

    This report examines whether participants in a study of treatments for marijuana dependence may have increased their use of alcohol when they reduced or ceased marijuana use. Participants were randomly assigned to one of four psychosocial treatments and followed at 3-month intervals for one-year. Findings are from 207 cases with data at posttreatment and at least one other follow-up. 73% of cases reported an increase of at least 10% in drinking days over their level at intake, and 65% reporte...

  6. Pre- and Peri-/Post-Compaction Follistatin Treatment Increases In Vitro Production of Cattle Embryos.

    Science.gov (United States)

    Zhenhua, Guo; Rajput, Sandeep K; Folger, Joseph K; Di, Liu; Knott, Jason G; Smith, George W

    2017-01-01

    Our previous studies demonstrated that maternal (oocyte derived) follistatin (FST) expression is positively associated with bovine oocyte competence and exogenous follistatin treatment during the pre-compaction period of development (d 1-3 post insemination) is stimulatory to bovine early embryogenesis in vitro [blastocyst rates and cell numbers/allocation to trophectoderm (TE)]. In the present study, bovine embryos were treated with exogenous follistatin during d 1-3, d 4-7 and d 1-7 post insemination to test the hypothesis that embryotropic effects of exogenous follistatin are specific to the pre-compaction period (d 1-3) of early embryogenesis. Follistatin treatment during d 4-7 (peri-/post-compaction period) of embryo culture increased proportion of embryos reaching blastocyst and expanded blastocyst stage and total cell numbers compared to controls, but blastocyst rates and total cell numbers were lower than observed following d 1-3 (pre-compaction) follistatin treatment. Follistatin supplementation during d 1-7 of embryo culture increased development to blastocyst and expanded blastocyst stages and blastocyst total cell numbers compared to d 1-3 and d 4-7 follistatin treatment and untreated controls. A similar increase in blastocyst CDX2 mRNA and protein (TE cell marker) was observed in response to d 1-3, d 4-7 and d 1-7 follistatin treatment. However, an elevation in blastocyst BMP4 protein (TE cell regulator) was observed in response to d 1-3 and d 1-7, but not d 4-7 (peri-/post-compaction) follistatin treatment. In summary, our study revealed the potential utility of follistatin treatment for increasing the success rate of in vitro embryo production in cattle. Such results also expand our understanding of the embryotropic actions of follistatin and demonstrate that follistatin actions on blastocyst development and cell allocation to the TE layer are not specific to the pre-compaction period.

  7. Treatment of acromegaly increases BMD but reduces trabecular bone score: a longitudinal study.

    Science.gov (United States)

    Godang, Kristin; Olarescu, Nicoleta Cristina; Bollerslev, Jens; Heck, Ansgar

    2016-08-01

    Bone turnover is increased in acromegaly. Despite normalization of bone turnover after treatment, the risk for vertebral fractures remains increased. Gonadal status, but not BMD, is correlated with vertebral fractures. Trabecular bone score (TBS) is related to bone microarchitecture. The aim of this study is to assess the longitudinal change in TBS and BMD following treatment for acromegaly. DESIGN, SETTING, PATIENTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: This longitudinal study included 48 patients with acromegaly between 2005 and 2015. BMD, TBS, and markers for bone turnover (P1NP and CTX-1) were measured at baseline and following treatment. Following treatment, the mean TBS decreased by 3.0 (±7.0) %, whereas the BMD at the lumbar spine (LS) increased by 3.2 (±4.9) % (both Pacromegaly affects TBS and BMD at LS in different manners. The reduction of bone turnover markers predicts the increase in BMD but not the decrease in TBS. The DXA changes were more pronounced in men. Alterations in trabecular bone architecture may explain the persistent fracture risk despite the increase in BMD after disease control. © 2016 European Society of Endocrinology.

  8. Increased Mindfulness Skills as Predictors of Reduced Trauma-Related Guilt in Treatment-Seeking Veterans.

    Science.gov (United States)

    Held, Philip; Owens, Gina P; Monroe, J Richard; Chard, Kathleen M

    2017-08-01

    The present study examined the predictive role of increased self-reported mindfulness skills on reduced trauma-related guilt in a sample of veterans over the course of residential treatment for posttraumatic stress disorder (PTSD; N = 128). The residential treatment consisted of seven weeks of intensive cognitive processing therapy (CPT) for PTSD, as well as additional psychoeducational groups, including seven sessions on mindfulness skills. Increased mindfulness skills describing, acting with awareness, and accepting without judgment were significantly associated with reductions in trauma-related guilt over the course of treatment. Increases in the ability to act with awareness and accept without judgment were significantly associated with reductions in global guilt, R(2) = .26, guilt distress, R(2) = .23, guilt cognitions, R(2) = .23, and lack of justification, R(2) = .11. An increase in the ability to accept without judgment was the only self-reported mindfulness skill that was associated with reductions in hindsight bias, β = -.34 and wrongdoing, β = -.44. Increases in self-reported mindfulness skills explained 15.1 to 24.1% of the variance in reductions in trauma-related guilt, suggesting that mindfulness skills may play a key role in reducing the experience of trauma-related guilt during psychotherapy. Our results provide preliminary support for the use of mindfulness groups as an adjunct to traditional evidence-based treatments aimed at reducing trauma-related guilt, though this claim needs to be tested further using experimental designs. Copyright © 2017 International Society for Traumatic Stress Studies.

  9. Increasing the sludge energy potential of wastewater treatment plants by introducing fine mesh sieves for primary treatment.

    Science.gov (United States)

    Paulsrud, Bjarne; Rusten, Bjørn; Aas, Bjørn

    2014-01-01

    The objective of this study was to compare some basic characteristics of sludge from fine mesh sieves (sieve sludge) with sludge from primary clarifiers (primary sludge) regarding their energy potential with a focus on anaerobic digestion and/or incineration. Nineteen samples of sludge from fine mesh sieve plants (most of them without fine screens and grit chambers as pre-treatment) and 10 samples of primary sludge were analysed for the content of dry solids (DS), volatile solids (VS), chemical oxygen demand (COD), calorific value and methane potential. The results demonstrated that the sieve sludges have significantly higher VS content and higher methane potential than primary sludges, clearly indicating an increased sludge energy potential if fine mesh sieves are used for primary treatment instead of primary clarifiers at wastewater treatment plants with anaerobic digesters. If the sludges from primary treatment are to be incinerated or used as fuel in cement kilns, there is no significant difference in energy potential (given as calorific values) for the two types of primary treatment.

  10. Increasing dependency of older people in nursing homes is associated with need for dental treatments

    Directory of Open Access Journals (Sweden)

    Zenthöfer A

    2014-12-01

    Full Text Available Andreas Zenthöfer, Peter Rammelsberg, Tomas Cabrera, Alexander Jochen Hassel Department of Prosthodontics, Dental School, University of Heidelberg, Heidelberg, Germany Abstract: To determine relationships between the need for dental treatments of institutionalized elderly people and cognitive impairment and the general level of care needed. Two hundred and sixty-eight residents of long-term care facilities in Germany were included in this study. Age, sex, diseases, number of frequently taken drugs, and location of the long-term care facility of the participants were recorded. For each participant, the need for care was assessed by use of the Barthel index (BI. Cognitive impairment was evaluated by use of the mini-mental state examination (MMSE. To assess dental treatment needs, the revised oral assessment guide (ROAG was applied for different oral health conditions, which were rated “healthy” or “treatment needed”. Spearman correlations were performed to evaluate associations between BI and MMSE and dental treatment needs. Statistical analysis revealed significant associations of BI (P<0.001 and MMSE (P=0.015 with the ROAG score. Increasing dependency and decreasing cognitive ability worsen oral health and increase the need for dental treatment. Keywords: elderly, dependency, Barthel index, treatment needs, oral health

  11. Improvement of district hospital service system to increase treatment adherence among tuberculosis patients in Pakistan.

    Science.gov (United States)

    Khan, Muhammad Shafiq; Suwannapong, Nawarat; Howteerakul, Nopporn; Pacheun, Oranut; Rajatanun, Titipat

    2011-05-01

    Adherence to medication regimen is essential for tuberculosis (TB) treatment success. We carried out quasi-experimental, single group intervention study at Rawalpindi District Hospital to improve TB patient treatment adherence using a Chronic Care Model (CCM). Ninety-nine newly diagnosed TB patients at the TB Clinic, Rawalpindi District Hospital, during February-March 2009, were included in the study. A set of four quality indicators were determined based on current scientific evidence: quality of service system, patient satisfaction, treatment adherence and cure rate. Care quality changes over time were analyzed by paired t-test. Significant improvements in service quality were seen post-intervention. Overall, the hospital service system quality improved to "good" (from 1.0% to 28.3%), and patient satisfaction increased to "good" (10.2% to 54.1%). Treatment adherence increased (from 23.2% to 56.1%). The quarterly cure rate increased notably (5.3% to 17.2%). The overall mean scores for hospital service system quality, patient satisfaction, and TB patient treatment adherence, improved significantly 6 month post-intervention (p<0.001).

  12. Natalizumab treatment leads to an increase in circulating CXCR3-expressing B cells

    Science.gov (United States)

    Penttilä, Tarja-Leena; Airas, Laura

    2016-01-01

    Objective: To study the effects of natalizumab treatment on subgroups of circulating peripheral blood B cell populations. Methods: We studied the proportions and absolute numbers of CD19+CD20+, CD10+, and CD5+ B cell populations, and determined very late activation antigen-4 and chemokine receptor CXCR3, CCR5, and CCR6 expression on B cells in the peripheral blood of 14 natalizumab-treated patients with relapsing-remitting multiple sclerosis. Five blood samples per patient were obtained longitudinally before and during the first year of treatment. Blood samples were analyzed by 6-color flow cytometry. Results: Proportions of B cells and CD10+ pre–B cells were significantly increased, and very late activation antigen-4 expression on the B cell surface was significantly decreased already after 1 week of natalizumab treatment. Natalizumab-induced sustained increase in the proportion and absolute number of CXCR3-expressing B cells was statistically significant after 1 month of treatment. There were no changes in the proportions of CCR5- or CCR6-expressing B cells. Conclusions: The rapid and persistent increase in circulating CXCR3-expressing B cells in response to natalizumab treatment possibly reflects the relevance of this chemokine receptor in controlling migration of B cells into the CNS in humans in vivo. PMID:27800533

  13. Pioglitazone utilization, efficacy & safety in Indian type 2 diabetic patients: A systematic review & comparison with European Medicines Agency Assessment Report

    Directory of Open Access Journals (Sweden)

    Sarayu A Pai

    2016-01-01

    Interpretation & conclusions: In India, probably due to lower dose, lower background incidence of bladder cancer and smaller sample size in epidemiological studies, association of bladder cancer with pioglitazone was not found to be significant. Reporting of CTs and adverse drug reactions to Clinical Trials Registry of India and Pharmacovigilance Programme of India, respectively, along with compliance studies with warning given in package insert and epidemiological studies with larger sample size are needed.

  14. Increasing Treatment Integrity through Negative Reinforcement: Effects on Teacher and Student Behavior

    Science.gov (United States)

    DiGennaro, Florence D.; Martens, Brian K.; McIntyre, Laura Lee

    2005-01-01

    The current study examined the extent to which treatment integrity was increased and maintained for 4 teachers in their regular classroom settings as a result of performance feedback and negative reinforcement. Teachers received daily written feedback about their accuracy in implementing an intervention and were able to avoid meeting with a…

  15. Treatment of human muscle cells with popular dietary supplements increase mitochondrial function and metabolic rate

    Directory of Open Access Journals (Sweden)

    Vaughan Roger A

    2012-11-01

    Full Text Available Abstract Background Obesity is a common pathology with increasing incidence, and is associated with increased mortality and healthcare costs. Several treatment options for obesity are currently available ranging from behavioral modifications to pharmaceutical agents. Many popular dietary supplements claim to enhance weight loss by acting as metabolic stimulators, however direct tests of their effect on metabolism have not been performed. Purpose This work identified the effects popular dietary supplements on metabolic rate and mitochondrial biosynthesis in human skeletal muscle cells. Methods Human rhabdomyosarcoma cells were treated with popular dietary supplements at varied doses for 24 hours. Peroxisome proliferator-activated receptor coactivator 1 alpha (PGC-1α, an important stimulator of mitochondrial biosynthesis, was quantified using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR. Mitochondrial content was measured using flow cytometry confirmed with confocal microscopy. Glycolytic metabolism was quantified by measuring extracellular acidification rate (ECAR and oxidative metabolism was quantified by measuring oxygen consumption rate (OCR. Total relative metabolism was quantified using WST-1 end point assay. Results Treatment of human rhabdomyosarcoma cells with dietary supplements OxyElite Pro (OEP or Cellucore HD (CHD induced PGC-1α leading to significantly increased mitochondrial content. Glycolytic and oxidative capacities were also significantly increased following treatment with OEP or CHD. Conclusion This is the first work to identify metabolic adaptations in muscle cells following treatment with popular dietary supplements including enhanced mitochondrial biosynthesis, and glycolytic, oxidative and total metabolism.

  16. Interventions to Increase Treatment Adherence in Pediatric Atopic Dermatitis: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Alexandria M. Bass

    2015-01-01

    Full Text Available Poor adherence to treatment is a major factor limiting treatment outcomes in patients with atopic dermatitis. The purpose of our systematic review is to identify techniques that have been tested to increase treatment adherence in atopic dermatitis. A MEDLINE search was performed for clinical trials focusing on interventions used to increase adherence in atopic dermatitis. Four articles were retrieved. References of these studies were analyzed yielding three more trials. The seven results were evaluated by comparing the intervention used to improve adherence, how adherence was assessed, and the outcome of the intervention tested. Different approaches to increase adherence such as written eczema action plans, educational workshops, extra office visits, and use of an atopic dermatitis educator were evaluated. All interventions increased adherence rates or decreased severity in patients, except for two. The MEDLINE search yielded limited results due to a lack of studies conducted specifically for atopic dermatitis and adherence was measured using different methods making the studies difficult to compare. Interventions including patient education, eczema action plans, and a quick return for a follow-up visit improve adherence, but based on the lack of clinical trials, developing new techniques to improve adherence could be as valuable as developing new treatments.

  17. Morphine treatment during juvenile isolation increases social activity and opioid peptides release in the adult rat.

    Science.gov (United States)

    Van den Berg, C L; Kitchen, I; Gerrits, M A; Spruijt, B M; Van Ree, J M

    1999-05-29

    The consequences of juvenile isolation and morphine treatment on general activity, social activity and endogenous opioid release during a social interaction test were investigated in the adult rat. Rats were either isolated or socially housed during weeks 4 and 5 of age and treated daily during this isolation period subcutaneously with either saline or morphine. Directly after a social interaction test at 10 weeks of age, rats were injected with [3H]-diprenorphine and subsequently prepared for in vivo autoradiography. The autoradiographic technique was used to visualise neuroanatomical changes in opioid receptor occupancy, probably reflecting changes in opioid peptide release, as a result of social activity. Juvenile isolation increased general activity during the social interaction test, an effect which was accompanied by a reduction of opioid receptor occupancy in many brain areas, suggesting an increased opioid peptide release as a consequence of socially-induced general activity. Morphine treatment in isolated rats caused an increase in adult social activity and enhanced opioid peptide release in some cortical regions and the ventral tegmental area as compared to saline treated rats. Both social activity and opioid receptor occupancy were unaffected by morphine treatment in non-isolated rats. The present study underscores the role of opioid systems in adult social behaviors as a consequence of juvenile isolation. The results suggest a relationship between social activity and opioid peptide release during social contact. Increased social activity seems to be accompanied by elevated opioid peptide release in distinct brain areas after morphine treatment during juvenile isolation.

  18. The Accelerated Intake: A Method for Increasing Initial Attendance to Outpatient Cocaine Treatment.

    Science.gov (United States)

    Festinger, David S.; And Others

    1996-01-01

    The effectiveness of offering same day appointments at an outpatient cocaine treatment program to increase intake attendance was examined. Seventy-eight clients were given standard or accelerated intake appointments. Significantly more clients who were given accelerated appointments attended the program. An accelerated intake procedure appears to…

  19. Itraconazole treatment reduces Batrachochytrium dendrobatidis prevalence and increases overwinter field survival in juvenile Cascades frogs.

    Science.gov (United States)

    Hardy, Bennett M; Pope, Karen L; Piovia-Scott, Jonah; Brown, Richard N; Foley, Janet E

    2015-01-15

    The global spread of the fungal pathogen Batrachochytrium dendrobatidis (Bd) has led to widespread extirpation of amphibian populations. During an intervention aimed at stabilizing at-risk populations, we treated wild-caught Cascades frogs Rana cascadae with the antifungal drug itraconazole. In fall 2012, we collected 60 recently metamorphosed R. cascadae from 1 of the 11 remnant populations in the Cascades Mountains (CA, USA). Of these, 30 randomly selected frogs were treated with itraconazole and the other 30 frogs served as experimental controls; all were released at the capture site. Bd prevalence was low at the time of treatment and did not differ between treated frogs and controls immediately following treatment. Following release, Bd prevalence gradually increased in controls but not in treated frogs, with noticeable (but still non-significant) differences 3 wk after treatment (27% [4/15] vs. 0% [0/13]) and strong differences 5 wk after treatment (67% [8/12] vs. 13% [1/8]). We did not detect any differences in Bd prevalence and load between experimental controls and untreated wild frogs during this time period. In spring 2013, we recaptured 7 treated frogs but none of the experimental control frogs, suggesting that over-winter survival was higher for treated frogs. The itraconazole treatment did appear to reduce growth rates: treated frogs weighed 22% less than control frogs 3 wk after treatment (0.7 vs. 0.9 g) and were 9% shorter than control frogs 5 wk after treatment (18.4 vs. 20.2 mm). However, for critically small populations, increased survival of the most at-risk life stage could prevent or delay extinction. Our results show that itraconazole treatment can be effective against Bd infection in wild amphibians, and therefore the beneficial effects on survivorship may outweigh the detrimental effects on growth.

  20. Expression of REST4 in human gliomas in vivo and influence of pioglitazone on REST in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Huan [Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008 (China); Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078 (China); Gao, Zhangfeng [Department of Neurosurgery, Second Xiangya Hospital of Central South University, Changsha 410008 (China); Wu, Nayiyuan; Zeng, Liu; Tang, Xinyue; Chen, Xiaoping; Liu, Zhaoqian; Zhang, Wei; Wang, Liansheng [Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008 (China); Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078 (China); Li, Zhi, E-mail: lizhi489@163.com [Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008 (China); Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078 (China)

    2015-08-07

    The repressor element-1 (RE1) silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) has an irreplaceable role during the differentiation of neurons. REST has multiple splice variants which link to various types of cancer. Previous work had highlighted the role of REST in glioma, where the expression of REST is enhanced. But whether alternative splicing of REST is expressed in glioma has not been described. Here, we show that a specific isoform REST4 is expressed in glioma specimens, and will influence the mRNA level of REST in vivo. Peroxisome proliferator-activated receptor-γ (PPARγ) agonists have a role of antineoplastic in various tumor cells, which including glioma cells. Moreover, study indicated that PPARγ agonist pioglitazone can promote alternative splicing of REST pre-mRNA. In this study, we selected pioglitazone as a tool drug to explore whether the role of pioglitazone in anti-glioma is mediated by regulating REST expression or promoting alternative splicing of REST in glioma cells. Results show that pioglitazone can inhibit proliferation and induce apoptosis of glioma cell in vitro, which may be mediated by down-regulating REST mRNA level but not by inducing alternative splicing of REST pre-mRNA. Our study firstly reports the expression of REST4 in glioma tissue samples. And we recommend that pioglitazone, which can reduce the expression level of REST, represents a promising drug for therapy of glioma. - Highlights: • A specific isoform REST4 is expressed in glioma specimens in vivo. • REST4 will influence the mRNA level of REST in vivo. • Pioglitazone can inhibit proliferation and induce apoptosis of glioma cells. • The role of pioglitazone in anti-glioma may be mediated by down-regulating REST.

  1. Formulation and evaluation of sustained release matrix tablets of pioglitazone hydrochloride using processed Aloe vera mucilage as release modifier

    Directory of Open Access Journals (Sweden)

    Manoj Choudhary

    2015-01-01

    Full Text Available Background: Natural gums and mucilage which hydrates and swells on contact with aqueous media are used as additives in the formulation of hydrophilic drug delivery system. Aim: The purpose of this study was to develop a new monolithic matrix system for complete delivery of Pioglitazone hydrochloride (HCl, in a zero-order manner over an extended time period using processed Aloe vera gel mucilage (PAG as a release modifier. Materials and Methods: The matrices were prepared by dry blending of selected ratios of polymer and ingredients using direct compression technique. Physicochemical properties of dried powdered mucilage of A. vera were studied. Various formulations of pioglitazone HCl and A. vera mucilage were prepared using different drug: Polymer ratios viz., 1:1, 1:2, 1:3, 1:4, 1:5 for PAG by direct compression technique. Results: The formulated matrix tablets were found to have better uniformity of weight and drug content with low statistical deviation. The swelling behavior and in vitro release rate characteristics were also studied. Conclusion: The study proved that the dried A. vera mucilage can be used as a matrix forming material for controlled release of Pioglitazone HCl matrix tablets.

  2. Influence of choroidal perfusion on retinal temperature increase during retinal laser treatments

    Science.gov (United States)

    Herrmann, Katharina; Flöhr, Christian; Stalljohann, Jens; Apiou-Sbirlea, Gabriela; Kandulla, Jochen; Birngruber, Reginald; Brinkmann, Ralf

    2007-07-01

    In most retinal laser treatments the therapeutic effect is initiated by a transient temperature increase at and around the retinal pigment epithelium (RPE). Especially in long exposure time treatments like Transpupillary Thermotherapy (TTT) choroidal perfusion has a strong influence on the realized temperature at the fundus. The fundus blood circulation and therefore the heat dissipation is influenced by the intraocular pressure (IOP), which is investigated in the study presented here. In order to reduce the choroidal perfusion, the IOP is increased by injection of physiological saline solution into the eye of anaesthetized rabbits. The fundus is irradiated with 3.64 W/cm2 by means of a TTT-laser (λ = 810 nm) for t = 20 s causing a retinal temperature increase. Realtime temperature determination at the irradiated spot is achieved by a non invasive optoacoustic technique. Perfusion can be reduced by increasing IOP, which leads to different temperature increases when irradiating the retina. This should be considered for long time laser treatments.

  3. Effect of price increase of adrenocorticotropic hormone on treatment practices of infantile spasms.

    Science.gov (United States)

    Wray, Carter D; Benke, Timothy A

    2010-09-01

    Intramuscular adrenocorticotropic hormone putatively constitutes the most efficacious treatment for infantile spasms. Adrenocorticotropic hormone in the United States is an "orphan drug," made by a single manufacturer. The price of adrenocorticotropic hormone increased almost 14-fold on August 27, 2007. We sought to evaluate the impact of this price increase on treatment practices at our institution, using a retrospective chart review of all children with infantile spasms treated during 2007-2009. We identified 97 patients whose spasms were treated using antiepileptic drugs, and we determined the length of stay for those hospitalized to initiate adrenocorticotropic hormone. Patients before the price increase were more likely to have been treated with adrenocorticotropic hormone as first medication, and were hospitalized 2.2 +/- 0.5 S.D. days for initiation. Patients after the price increase were more likely to have been treated initially with oral antiepileptic drugs rather than adrenocorticotropic hormone (P price increase were hospitalized significantly longer (5.1 +/- 0.6 days S.D., P < 0.001). Treatment choices need to be evidence-based, but other factors often influence them. Copyright 2010 Elsevier Inc. All rights reserved.

  4. 吡格列酮降低非糖尿病患者冠状动脉药物洗脱支架再狭窄的研究%Study of pioglitazone reducing in-stent restenosis on non-diabetic patients with drug-eluting stents

    Institute of Scientific and Technical Information of China (English)

    魏广和; 刘立新; 王铁成; 王建军; 高荣华; 张韶辉

    2012-01-01

    Objective:To investigate the effects and mechanisms of pioglitazone on in-stent restenosis after coronary stenting in nondiabetic patients with coronary artery disease. Method:One hundred and twenty-eight nondia-betic patients after rapamycin eluting stent implantation were randomly assigned to pioglitazone (pioglitazone group, h=71, 30 mg/d) or placebo (control group, n = 57) treatment in addition to standard therapy. Selective coronary angiography was performed at 6 —8 months follow-up. Fasting blood glucose, fasting insulin, leptin, adiponectin as well as lipid parameters were measured at study entry and 6 — 8 months follow-up. In addition, the homeostasis model assessment of insulin resistance index (HOMA-IR) of patients were calculated. Result: The incidence of in-stent restenosis in pioglitazone group was significantly lower than the control group (2.82% vs 12. 28% , P = 0. 037). After 6 — 8 months follow-up, there was no significant difference of serum lipids and fasting blood glucose in 2 group. However, HOMA-IR, adiponectin and A/L in pioglitazone group were significantly different from the control group. Conclusion: Pioglitazone can reduce the restenosis of non-diabetic patients with drug-eluting stents. Improving insulin resistance and endothelial dysfunction is probably the important mechanisms of pioglitazone preventing in-stent restenosis.%目的:探讨吡格列酮对非糖尿病患者冠状动脉(冠脉)支架内再狭窄的影响及其可能机制.方法:选择置入雷帕霉素洗脱支架的非糖尿病患者128例,并排除糖耐量异常者,随机分成吡格列酮组(71例)和对照组(57例),吡格列酮组在对照组常规治疗的基础上加用吡格列酮(30mg,qd);冠脉支架置入术后6~8个月行选择性冠脉造影术,于治疗前及随访6~8个月复查时先后分别测定血脂、空腹血糖、空腹胰岛素、血清瘦素及血清脂联素,并计算胰岛素抵抗指数(HOMA-IR).结果:吡格列酮组支架内再

  5. Low dose of corticosterone treatment with exercise increases hippocampal cell proliferation, and improves cognition

    Institute of Scientific and Technical Information of China (English)

    Suk-Yu Yau; Jada Chia-Di Lee; Benson Wui-Man Lau; Tatia M.C. Lee; Yick-Pang Ching; Siu-Wa Tang; Kwok-Fai So

    2011-01-01

    Intermediate level of stress is beneficial for brain functions, whereas extreme low level or high level of stress is deleterious. We have previously shown that chronic exposure to high doses of corticosterone (CORT) suppressed hippocampal plasticity and physical exercise in terms of running counteracted the detrimental effects of CORT treatment. We aimed to study whether a mild stress, that mimicked by a treatment with low CORT dose, improved hippocampal plasticity in terms of hippocampal cell proliferation and dendritic remodeling, and to examine whether running with CORT treatment showed an additive effect on improving hippocampal plasticity. The rats were treated with 20 mg/kg CORT for 14 days with or without running, followed by Morris water maze test or forced swim test. The hippocampal proliferating cells was labeled by intraperitoneal injection of 5-bromo-2'-deoxyuridine. The dendritic morphology was analyzed using Golgi staining method. Treatment with 20 mg/kg CORT alone yielded a higher number of hippocampal cell proliferation and significantly increased dendritic branching compared to vehicle-treated non-runners, but had no behavioral effects. In contrast, CORT treatment with running showed an additive increase in hippocampal cell proliferation and dendritic remodeling that was associated with improved spatial learning and decreased depression-like behavior; however, there was no additive improvement in behavior compared to vehicle-treated runners. These findings suggest that mild stress does not always cause detrimental effect on the brain, and combining mild stress with running could promote hippocampal plasticity via inducing cell proliferation and dendritic remodeling.

  6. Chronic pramipexole treatment increases tolerance for sucrose in normal and ventral tegmental lesioned rats.

    Directory of Open Access Journals (Sweden)

    David eDARDOU

    2015-01-01

    Full Text Available The loss of dopamine neurons observed in Parkinson’s disease (PD elicits severe motor control deficits which are reduced by the use of dopamine agonists. However, recent works have indicated that D3-preferential agonists such as pramipexole can induce impulse control disorders such as food craving or compulsive eating. In the present study, we performed an intermittent daily feeding experiment to assess the effect of chronic treatment by pramipexole and VTA bilateral lesion on tolerance for sucrose solution. The impact of such chronic treatment on spontaneous locomotion and spatial memory was also examined. Changes in sucrose tolerance could indicate the potential development of a change in food compulsion or addiction related to the action of pramipexole. Neither the bilateral lesion of the VTA nor chronic treatment with pramipexole altered the spontaneous locomotion or spatial memory in rats. Rats without pramipexole treatment quickly developed a stable intake of sucrose solution in the 12h access phase. On the contrary, when under daily pramipexole treatment, rats developed a stronger and ongoing escalation of their sucrose solution intakes. In addition, we noted that the change in sucrose consumption was sustained by an increase of the expression of the dopamine 3 receptor in the core and the shell regions of the nucleus accumbens. The present results may suggest that long term stimulation of the dopamine 3 receptor in animals induces a strong increase in sucrose consumption, indicating an effect of this receptor on certain pathological aspects of food eating.

  7. Chronic pramipexole treatment increases tolerance for sucrose in normal and ventral tegmental lesioned rats.

    Science.gov (United States)

    Dardou, David; Chassain, Carine; Durif, Franck

    2014-01-01

    The loss of dopamine neurons observed in Parkinson's disease (PD) elicits severe motor control deficits which are reduced by the use of dopamine agonists. However, recent works have indicated that D3-preferential agonists such as pramipexole can induce impulse control disorders (ICDs) such as food craving or compulsive eating. In the present study, we performed an intermittent daily feeding experiment to assess the effect of chronic treatment by pramipexole and VTA bilateral lesion on tolerance for sucrose solution. The impact of such chronic treatment on spontaneous locomotion and spatial memory was also examined. Changes in sucrose tolerance could indicate the potential development of a change in food compulsion or addiction related to the action of pramipexole. Neither the bilateral lesion of the VTA nor chronic treatment with pramipexole altered the spontaneous locomotion or spatial memory in rats. Rats without pramipexole treatment quickly developed a stable intake of sucrose solution in the 12 h access phase. On the contrary, when under daily pramipexole treatment, rats developed a stronger and ongoing escalation of their sucrose solution intakes. In addition, we noted that the change in sucrose consumption was sustained by an increase of the expression of the Dopamine D3 receptor in the core and the shell regions of the nucleus accumbens. The present results may suggest that long-term stimulation of the Dopamine D3 receptor in animals induces a strong increase in sucrose consumption, indicating an effect of this receptor on certain pathological aspects of food eating.

  8. Glioblastoma Treatment: Bypassing the Toxicity of Platinum Compounds by Using Liposomal Formulation and Increasing Treatment Efficiency With Concomitant Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Charest, Gabriel; Sanche, Leon [Center for Research in Radiotherapy, Department of Nuclear Medicine and Radiobiology, Universite de Sherbrooke, Sherbrooke, Quebec (Canada); Fortin, David; Mathieu, David [Department of Surgery, Division of Neurosurgery, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec (Canada); Paquette, Benoit, E-mail: Benoit.Paquette@USherbrooke.ca [Center for Research in Radiotherapy, Department of Nuclear Medicine and Radiobiology, Universite de Sherbrooke, Sherbrooke, Quebec (Canada)

    2012-09-01

    Purpose: Treatments of glioblastoma with cisplatin or oxaliplatin only marginally improve the overall survival of patients and cause important side effects. To prevent adverse effects, improve delivery, and optimize the tumor response to treatment in combination with radiotherapy, a potential approach consists of incorporating the platinum agent in a liposome. Methods and Materials: In this study, cisplatin, oxaliplatin, carboplatin, Lipoplatin (the liposomal formulation of cisplatin), and Lipoxal (the liposomal formulation of oxaliplatin) were tested on F98 glioma orthotopically implanted in Fischer rats. The platinum compounds were administered by intracarotid infusion and were assessed for the ability to reduce toxicity, improve cancer cell uptake, and increase survival of animals when combined or not combined with radiotherapy. Results: The tumor uptake was 2.4-fold more important for Lipoxal than the liposome-free oxaliplatin. Lipoxal also improved the specificity of oxaliplatin as shown by a higher ratio of tumor to right hemisphere uptake. Surprisingly, Lipoplatin led to lower tumor uptake compared with cisplatin. However, Lipoplatin had the advantage of largely reducing the toxicity of cisplatin and allowed us to capitalize on the anticancer activity of this agent. Conclusion: Among the five platinum compounds tested, carboplatin showed the best increase in survival when combined with radiation for treatment of glioma implanted in Fischer rats.

  9. Combined cisplatin and aurora inhibitor treatment increase neuroblastoma cell death but surviving cells overproduce BDNF.

    Science.gov (United States)

    Polacchini, Alessio; Albani, Clara; Baj, Gabriele; Colliva, Andrea; Carpinelli, Patrizia; Tongiorgi, Enrico

    2016-07-15

    Drug-resistance to chemotherapics in aggressive neuroblastoma (NB) is characterized by enhanced cell survival mediated by TrkB and its ligand, brain-derived neurotrophic factor (BDNF); thus reduction in BDNF levels represent a promising strategy to overcome drug-resistance, but how chemotherapics regulate BDNF is unknown. Here, cisplatin treatment in SK-N-BE neuroblastoma upregulated multiple BDNF transcripts, except exons 5 and 8 variants. Cisplatin increased BDNF mRNA and protein, and enhanced translation of a firefly reporter gene flanked by BDNF 5'UTR exons 1, 2c, 4 or 6 and 3'UTR-long. To block BDNF translation we focused on aurora kinases inhibitors which are proposed as new chemotherapeutics. NB cell survival after 24 h treatment was 43% with cisplatin, and 22% by cisplatin+aurora kinase inhibitor PHA-680632, while the aurora kinases inhibitor alone was less effective; however the combined treatment induced a paradoxical increase of BDNF in surviving cells with strong translational activation of exon6-3'UTR-long transcript, while translation of BDNF transcripts 1, 2C and 4 was suppressed. In conclusion, combined cisplatin and aurora kinase inhibitor treatment increases cell death, but induces BDNF overproduction in surviving cells through an aurora kinase-independent mechanism.

  10. Do hypertension and diuretic treatment in pregnancy increase the risk of schizophrenia in offspring?

    DEFF Research Database (Denmark)

    Sørensen, Holger J; Mortensen, Erik L; Reinisch, June M

    2003-01-01

    OBJECTIVE: Diuretics prescribed after the first trimester for treatment of hypertension in pregnant women may interfere with normal plasma volume expansion and cause volume depletion. The authors hypothesized that prenatal exposure to diuretics and maternal hypertension might disrupt fetal...... neurodevelopment and increase the risk of schizophrenia in offspring. METHOD: Using data from the Copenhagen Perinatal Cohort of individuals born between 1959 and 1961, the authors studied the relationship of maternal hypertension and diuretic treatment during pregnancy with the risk of schizophrenia (ICD-8 code...... 295) in the offspring. Prenatal medical information was linked to the Danish National Psychiatric Register. The effects of maternal hypertension and diuretic treatment were adjusted for the maternal history of schizophrenia, social status of the family breadwinner, mother's age, and concomitant drug...

  11. Trigger Finger Appearing as Gradually Increasing Digital Nerve Disorder after Surgical Treatment

    Directory of Open Access Journals (Sweden)

    Hiroyuki Tsuchie

    2013-01-01

    Full Text Available Trigger finger is a common disease, and operative treatments are often applied for it. Digital nerve injury is one of the complications of this surgical treatment, and paresthesia and sensory disturbance occur early after the operation. This paper presents a case of trigger finger appearing gradually as increasing digital nerve disorder after surgical treatment. In the second surgery, scar tissue covered the palmar MP joint where the A1 pulley had existed before, and palmar digital neurovascular tissue of the ulnar side was found on the inside of the scar. The ulnar digital nerve showed swelling like a neuroma, and bilateral digital nerves existed nearer to the center of the flexor pollicis longus tendon than normal digital nerves. Even when we operate on trigger finger by open release, we should create an appropriate surgical space for observation and be careful of digital nerve injury.

  12. New treatment options for infections caused by increasingly antimicrobial-resistant Neisseria gonorrhoeae.

    Science.gov (United States)

    Lee, Hyukmin; Lee, Kyungwon; Chong, Yunsop

    2016-01-01

    The emergence of high-level resistance to ceftriaxone is giving rise to serious concern about absence of effective treatment options to cure gonococcal infections. Increasing the dosage regimen can be applied to ceftriaxone and azithromycin, but the emergence of high-level resistance has already been reported. Spectinomycin is another active drug but has low efficacy in the treatment of pharyngeal gonorrhoea. Conventional antibiotics could be introduced for gonococcal treatment, but they have some limitations, such as the absence of clinical trials and breakpoint. Combining antibiotics is another promising method to cure patients and to prevent the emergence of resistance. The most important strategy to maintain the efficacy of antibiotics is rapid detection and dissemination control of novel resistant isolate.

  13. Do hypertension and diuretic treatment in pregnancy increase the risk of schizophrenia in offspring?

    DEFF Research Database (Denmark)

    Sørensen, Holger J; Mortensen, Erik Lykke; Reinisch, June M;

    2003-01-01

    295) in the offspring. Prenatal medical information was linked to the Danish National Psychiatric Register. The effects of maternal hypertension and diuretic treatment were adjusted for the maternal history of schizophrenia, social status of the family breadwinner, mother's age, and concomitant drug......OBJECTIVE: Diuretics prescribed after the first trimester for treatment of hypertension in pregnant women may interfere with normal plasma volume expansion and cause volume depletion. The authors hypothesized that prenatal exposure to diuretics and maternal hypertension might disrupt fetal...... neurodevelopment and increase the risk of schizophrenia in offspring. METHOD: Using data from the Copenhagen Perinatal Cohort of individuals born between 1959 and 1961, the authors studied the relationship of maternal hypertension and diuretic treatment during pregnancy with the risk of schizophrenia (ICD-8 code...

  14. Warming rather than increased precipitation increases soil recalcitrant organic carbon in a semiarid grassland after 6 years of treatments.

    Directory of Open Access Journals (Sweden)

    Xiaoqi Zhou

    Full Text Available Improved understanding of changes in soil recalcitrant organic carbon (C in response to global warming is critical for predicting changes in soil organic C (SOC storage. Here, we took advantage of a long-term field experiment with increased temperature and precipitation to investigate the effects of warming, increased precipitation and their interactions on SOC fraction in a semiarid Inner Mongolian grassland of northern China since April 2005. We quantified labile SOC, recalcitrant SOC and stable SOC at 0-10 and 10-20 cm depths. Results showed that neither warming nor increased precipitation affected total SOC and stable SOC at either depth. Increased precipitation significantly increased labile SOC at the 0-10 cm depth. Warming decreased labile SOC (P = 0.038 and marginally but significantly increased recalcitrant SOC at the 10-20 cm depth (P = 0.082. In addition, there were significant interactive effects of warming and increased precipitation on labile SOC and recalcitrant SOC at the 0-10 cm depth (both P<0.05, indicating that that results from single factor experiments should be treated with caution because of multi-factor interactions. Given that the absolute increase of SOC in the recalcitrant SOC pool was much greater than the decrease in labile SOC, and that the mean residence time of recalcitrant SOC is much greater, our results suggest that soil C storage at 10-20 cm depth may increase with increasing temperature in this semiarid grassland.

  15. Free ammonia pre-treatment of secondary sludge significantly increases anaerobic methane production.

    Science.gov (United States)

    Wei, Wei; Zhou, Xu; Wang, Dongbo; Sun, Jing; Wang, Qilin

    2017-07-01

    Energy recovery in the form of methane from sludge/wastewater is restricted by the poor and slow biodegradability of secondary sludge. An innovative pre-treatment technology using free ammonia (FA, i.e. NH3) was proposed in this study to increase anaerobic methane production. The solubilisation of secondary sludge was significantly increased after FA pre-treatment at up to 680 mg NH3-N/L for 1 day, under which the solubilisation (i.e. 0.4 mg SCOD/mg VS; SCOD: soluble chemical oxygen demand; VS: volatile solids) was >10 times higher than that without FA pre-treatment (i.e. 0.03 mg SCOD/mg VS). Biochemical methane potential assays showed that FA pre-treatment at above 250 mg NH3-N/L is effective in improving anaerobic methane production. The highest improvement in biochemical methane potential (B0) and hydrolysis rate (k) was achieved at FA concentrations of 420-680 mg NH3-N/L, and was determined as approximately 22% (from 160 to 195 L CH4/kg VS added) and 140% (from 0.22 to 0.53 d(-1)) compared to the secondary sludge without pre-treatment. More analysis revealed that the FA induced improvement in B0 and k could be attributed to the rapidly biodegradable substances rather than the slowly biodegradable substances. Economic and environmental analyses showed that the FA-based technology is economically favourable and environmentally friendly. Since this FA technology aims to use the wastewater treatment plants (WWTPs) waste (i.e. anaerobic digestion liquor) to enhance methane production from the WWTPs, it will set an example for the paradigm shift of the WWTPs from 'linear economy' to 'circular economy'. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Exogenous methyl jasmonate treatment increases glucosinolate biosynthesis and quinone reductase activity in kale leaf tissue.

    Science.gov (United States)

    Ku, Kang-Mo; Jeffery, Elizabeth H; Juvik, John A

    2014-01-01

    Methyl jasmonate (MeJA) spray treatments were applied to the kale varieties 'Dwarf Blue Curled Vates' and 'Red Winter' in replicated field plantings in 2010 and 2011 to investigate alteration of glucosinolate (GS) composition in harvested leaf tissue. Aqueous solutions of 250 µM MeJA were sprayed to saturation on aerial plant tissues four days prior to harvest at commercial maturity. The MeJA treatment significantly increased gluconasturtiin (56%), glucobrassicin (98%), and neoglucobrassicin (150%) concentrations in the apical leaf tissue of these genotypes over two seasons. Induction of quinone reductase (QR) activity, a biomarker for anti-carcinogenesis, was significantly increased by the extracts from the leaf tissue of these two cultivars. Extracts of apical leaf tissues had greater MeJA mediated increases in phenolics, glucosinolate concentrations, GS hydrolysis products, and QR activity than extracts from basal leaf tissue samples. The concentration of the hydrolysis product of glucoraphanin, sulforphane was significantly increased in apical leaf tissue of the cultivar 'Red Winter' in both 2010 and 2011. There was interaction between exogenous MeJA treatment and environmental conditions to induce endogenous JA. Correlation analysis revealed that indole-3-carbanol (I3C) generated from the hydrolysis of glucobrassicin significantly correlated with QR activity (r = 0.800, Pkale leaf tissues of both cultivars in 2011. Correlation analysis of these results indicated that sulforaphane, NI3C, neoascorbigen, I3C, and diindolylmethane were all significantly correlated with QR activity. Thus, increased QR activity may be due to combined increases in phenolics (quercetin and kaempferol) and GS hydrolysis product concentrations rather than by individual products alone.

  17. High-dose thalidomide increases the risk of peripheral neuropathy in the treatment of ankylosing spondylitis

    Directory of Open Access Journals (Sweden)

    Hong-xia Xue

    2015-01-01

    Full Text Available Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among ankylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treatments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the < 6 months medication and ≥ 6 months medication groups. There were no differences in the mean age, gender, or daily dose between the two groups. The incidence of peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclusion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide.

  18. Increasing Treatment Seeking Among at-Risk Service Members Returning from Warzones

    Science.gov (United States)

    2016-03-01

    stakeholders place on developing and implementing a comprehensive program to reduce suicide among U.S. service members and Veterans. Rates of suicide ...SUPPLEMENTARY NOTES 14. ABSTRACT We propose a randomized controlled clinical trial of 1,200 military service members who are at increased risk for suicide but...by phone, and has been shown to promote treatment-seeking including in a preliminary study of OEF/OIF Veterans with elevated posttraumatic stress

  19. Statin treatment increases lifespan and improves cardiac health in Drosophila by decreasing specific protein prenylation.

    Directory of Open Access Journals (Sweden)

    Stephen R Spindler

    Full Text Available Statins such as simvastatin are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase inhibitors and standard therapy for the prevention and treatment of cardiovascular diseases in mammals. Here we show that simvastatin significantly increased the mean and maximum lifespan of Drosophila melanogaster (Drosophila and enhanced cardiac function in aging flies by significantly reducing heart arrhythmias and increasing the contraction proportion of the contraction/relaxation cycle. These results appeared independent of internal changes in ubiquinone or juvenile hormone levels. Rather, they appeared to involve decreased protein prenylation. Simvastatin decreased the membrane association (prenylation of specific small Ras GTPases in mice. Both farnesyl (L744832 and type 1 geranylgeranyl transferase (GGTI-298 inhibitors increased Drosophila lifespan. These data are the most direct evidence to date that decreased protein prenylation can increase cardiac health and lifespan in any metazoan species, and may explain the pleiotropic (non-cholesterol related health effects of statins.

  20. Treatment with insulin analog X10 and IGF-1 increases growth of colon cancer allografts.

    Directory of Open Access Journals (Sweden)

    Henning Hvid

    Full Text Available Obesity and type 2 diabetes are associated with an increased risk for development of certain forms of cancer, including colon cancer. The publication of highly controversial epidemiological studies in 2009 raised the possibility that use of the insulin analog glargine increases this risk further. However, it is not clear how mitogenic effects of insulin and insulin analogs measured in vitro correlate with tumor growth-promoting effects in vivo. The aim of this study was to examine possible growth-promoting effects of native human insulin, insulin X10 and IGF-1, which are considered positive controls in vitro, in a short-term animal model of an obesity- and diabetes-relevant cancer. We characterized insulin and IGF-1 receptor expression and the response to treatment with insulin, X10 and IGF-1 in the murine colon cancer cell line (MC38 cells in vitro and in vivo. Furthermore, we examined pharmacokinetics and pharmacodynamics and monitored growth of MC38 cell allografts in mice with diet-induced obesity treated with human insulin, X10 and IGF-1. Treatment with X10 and IGF-1 significantly increased growth of MC38 cell allografts in mice with diet-induced obesity and we can therefore conclude that supra-pharmacological doses of the insulin analog X10, which is super-mitogenic in vitro and increased the incidence of mammary tumors in female rats in a 12-month toxicity study, also increase growth of tumor allografts in a short-term animal model.

  1. Increased Oocyte Production after Acupuncture Treatment during Superovulation Process in Mice

    Institute of Scientific and Technical Information of China (English)

    Chun-lan JIN; Kazuo Tohya; Koichi Kuribayashi; Michio Kimura; Yuki-hisa Hirao

    2009-01-01

    Objective To investigate whether acupuncture treatment during superovulation process improves ovarian response and increases egg production. Methods ICR female mice aged 12-15 weeks were divided into control group, anaesthesia group and acupuncture group. Female mice were injected intraperitoneally with pregnant mare's serum gonadotropin (PMSG), followed by human chorionic gonadotropin (hCG) injection 56 h later. Anaesthesia group and acupuncture group were anaesthetized three times by injecting 10% nembutal solution according to 7.5-10.0 μl/g weight. Acupuncture group was treated three times with puncture Sanyinjiao Points(SP6) under anaesthesia. After 17 h of hCG injection, eggs were recovered and ovaries were isolated. Matured eggs were counted, ovarian histology and expression of follicle stimulating hormone receptor(FSH-R) in ovary were analyzed.Results Acupuncture treatment statistically increased the number of ovulated eggs. Histological section showed that some matured follicles left in the ovaries of control and anaesthesia groups after ovulation. On the contrary, all matured follicles ruptured and converted into corpus lutea in Acupuncture group. Expression of FSH-R in ovary was decreased in acupuncture group compared with those of the two others.Conclusion Acupuncture treatment during superovulation process improves ovarianresponse so as to increase egg production. The positive effect of acupuncture may beassociated with regulated FSH-R expression.

  2. Effects of Pioglitazone on the Proliferation and Apoptosis of Human Gastric Cancer Cell Line SGC7901%吡格列酮对人胃癌 SGC7901细胞增殖和凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    陈静波; 陈巧; 郑建萍; 崔同建; 林俊锦; 刘振华; 李德育; 张桂枫; 蒋桂成; 陈峥

    2015-01-01

    Objectives To research the effects of pioglitazone on SGC7901 human gastric cancer cell line. Methods After induced by 5 ng·mL-1 TGF-β1, the SGC7901 human gastric cancer cell line in the research groups were treated by pioglitazone with different concentrations (5, 10, 20, 25 μmol·L-1) for different times (0, 12, 24, 48, 72 h). The control group had no medicament of pioglitazone. Then the proliferation and apoptosis of gastric cancer cells was detected respectively by MTT and flow cytometry method. The real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was applied to detect the gene expression level of peroxisome proliferator-activated receptorγ (PPARγ). Results Within the concentration range of 5~40 μmol·L-1, pioglitazone inhibited the growth of 5 ng·ml-1 TGF-β1 induced SGC7901 cells in a dose and time dependent manner (P<0.05). After treated by 10 μmol·L-1 of pioglitazone for 12 h, the apoptosis rate of TGF-β1 induced SGC7901 cell was increased significantly as compared with the con-trol group, and it was increased gradually along with the increase of the dose and time and reached the highest at 72 h (P<0.01). The PPARγmRNA expression level was also gradually upregulated along with the increase of the concentration of pioglitazone and treat-ing time, and difference had statistical significance (P<0.05). Conclusion Pioglitazone could inhibit the growth and promote the ap-optosis of TGF-β1 induced gastric cancer SGC7901 cells in a dose and time dependent manner through upregulating the expression of the PPARγ.%目的:研究吡格列酮对人胃癌 SGC7901细胞株体外生长的影响。方法采用5 ng·mL-1 TGF-β1诱导胃癌SGC7901细胞24 h 后,给予不同浓度(0、5、10、20、40μmol·L-1)吡格列酮处理不同时间(0、12、24、48、72 h),分别采用MTT 法和流式细胞术检测细胞增殖和细胞凋亡情况,同时采用实时荧光定量聚合酶链反应技术

  3. Oral treatment with ACCUTANE does not increase measures of anhedonia or depression in rats.

    Science.gov (United States)

    Ferguson, Sherry A; Cisneros, F Javier; Hanig, Joseph P; Berry, Kimberly J

    2007-01-01

    Reports of depression and/or suicide with ACCUTANE (13-cis-retinoic acid (13-cis-RA)) use prompted studies in a rodent model to ascertain its potential effects. Previously, there were no effects on measures of anhedonia (intake of a saccharin-flavored solution) and depression (forced swim test (FST) behaviors) in rats treated with 7.5 or 22.5 mg/kg 13-cis-RA [S.A. Ferguson, F.J. Cisneros, B. Gough, J.P. Hanig, K.J. Berry, Chronic oral treatment with 13-cis-retinoic acid (isotretinoin) or all-trans-retinoic acid does not alter depression-like behaviors in rats, Toxicol. Sci. 87 (2005) 451-459.]. Here, dose and temporal thresholds were investigated by increasing the maximum 13-cis-RA dose to 30 mg/kg, extending treatment duration, and measuring behaviors repeatedly. Beginning on post-natal day 59, male and female Sprague-Dawley rats were gavaged with soybean oil, 7.5 or 30 mg/kg/day of 13-cis-RA for approximately 19 weeks. FST behaviors were measured after 24, 82, and 131 treatment days and saccharin intake (0.03% solution) was measured at baseline and after 14, 35, 56, and 112 treatment days. Body weight and food intake were not altered by treatment. FST durations of swim, climb/struggle, and immobility were unaffected by 13-cis-RA at any time during treatment. More males than females required "rescue" in the FST but there was no treatment effect on number of rats requiring early removal. 13-cis-RA treatment had no effects on saccharin intake at any time. Given that the 7.5 mg/kg dose produces serum levels which parallel those of humans [S.A. Ferguson, P.H. Siitonen, F.J. Cisneros, B. Gough, J.F. Young, Steady state pharmacokinetics of oral treatment with 13-cis-retinoic acid or all-trans-retinoic acid in male and female adult rats, Basic Clin. Pharmacol. Toxicol 98 (2006) 582-587.], these results are quite relevant. Combined with previous results, these results provide further evidence that 13-cis-RA does not produce behavioral alterations indicative of depression

  4. Chronic lithium treatment increased intracellular S100ß levels in rat primary neuronal culture.

    Directory of Open Access Journals (Sweden)

    Masoumeh Emamghoreishi

    2015-02-01

    Full Text Available S100ß a neurotrophic factor mainly released by astrocytes, has been implicated in the pathogenesis of bipolar disorder. Thus, lithium may exert its neuroprotective effects to some extent through S100ß. Furthermore, the possible effects of lithium on astrocytes as well as on interactions between neurons and astrocytes as a part of its mechanisms of actions are unknown. This study was undertaken to determine the effect of lithium on S100β in neurons, astrocytes and a mixture of neurons and astrocytes. Rat primary astrocyte, neuronal and mixed neuro-astroglia cultures were prepared from cortices of 18-day's embryos. Cell cultures were exposed to lithium (1mM or vehicle for 1day (acute or 7 days (chronic. RT-PCR and ELISA determined S100β mRNA and intra- and extracellular protein levels. Chronic lithium treatment significantly increased intracellular S100β in neuronal and neuro-astroglia cultures in comparison to control cultures (P<0.05. Acute and chronic lithium treatments exerted no significant effects on intracellular S100β protein levels in astrocytes, and extracellular S100β protein levels in three studied cultures as compared to control cultures. Acute and chronic lithium treatments did not significantly alter S100β mRNA levels in three studied cultures, compared to control cultures. Chronic lithium treatment increased intracellular S100ß protein levels in a cell-type specific manner which may favor its neuroprotective action. The findings of this study suggest that lithium may exert its neuroprotective action, at least partly, by increasing neuronal S100ß level, with no effect on astrocytes or interaction between neurons and astrocytes.

  5. FOXO1 Content Is Reduced in Cystic Fibrosis and Increases with IGF-I Treatment

    Directory of Open Access Journals (Sweden)

    Arianna Smerieri

    2014-10-01

    Full Text Available Cystic fibrosis-related diabetes is to date the most frequent complication in cystic fibrosis (CF. The mechanisms underlying this condition are not well understood, and a possible role of insulin resistance is debated. We investigated insulin signal transduction in CF. Total insulin receptor, IRS1, p85 PI3K, and AKT contents were substantially normal in CF cells (CFBE41o-, whereas winged helix forkhead (FOXO1 contents were reduced both in baseline conditions and after insulin stimulation. In addition, CF cells showed increased ERK1/2, and reduced β2 arrestin contents. No significant change in SOCS2 was observed. By using a CFTR inhibitor and siRNA, changes in FOXO1 were related to CFTR loss of function. In a CF-affected mouse model, FOXO1 content was reduced in the muscle while no significant difference was observed in liver and adipose tissue compared with wild-type. Insulin-like growth factor 1 (IGF-I increased FOXO1 content in vitro and in vivo in muscle and adipose tissue. In conclusion; we present the first description of reduced FOXO1 content in CF, which is compatible with reduced gluconeogenesis and increased adipogenesis, both features of insulin insensitivity. IGF-I treatment was effective in increasing FOXO1, thereby suggesting that it could be considered as a potential treatment in CF patients possibly to prevent and treat cystic fibrosis-related diabetes.

  6. INCREASED OIL RECOVERY FROM MATURE OIL FIELDS USING GELLED POLYMER TREATMENTS

    Energy Technology Data Exchange (ETDEWEB)

    G.P. Willhite; D.W. Green; C.S. McCool

    2003-05-01

    Gelled polymer treatments are applied to oil reservoirs to increase oil production and to reduce water production by altering the fluid movement within the reservoir. This report describes the results of a three-year research program aimed at reducing barriers to the widespread use of gelled polymer treatments by (1) developing methods to predict gel behavior during placement in matrix rock and fractures, (2) determining the persistence of permeability reduction after gel placement, and (3) developing methods to design production well treatments to control water production. The work focused on the gel system composed of polyacrylamide and chromium acetate. The molar mass of the polymer was about six million. Chromium(III) acetate reacted and formed crosslinks between polymer molecules. The crosslinked polymer molecules, or pre-gel aggregates, combine and grow to eventually form a 3-dimensional gel. A fundamental study to characterize the formation and growth of pre-gel aggregates was conducted. Two methods, flow field-flow fractionation (FFFF) and multi-angle laser light scattering (MALLS) were used. Studies using FFFF were inconclusive. Data taken using MALLS showed that at the gel time the average molar mass of gel aggregates increased by a factor of about three while the average size increase was approximately 50%. Increased acetate concentration in the gelant increases the gel time. The in situ performance of an added-acetate system was investigated to determine the applicability for in-depth treatments. Increased acetate concentrations delayed the development of increased flow resistance during gelant injection in short sandpacks. The development of increased flow resistance (in situ gelation) was extended from 2 to 34 days by increasing the acetate-to-chromium ratio from 38 to 153. In situ gelation occurred at a time that was approximately 22% of the bulk gelation time. When carbonate rocks are treated with gel, chromium retention in the rock may limit in

  7. Increased trends in the use of treatment-limiting decisions in a regional neurosurgical unit.

    Science.gov (United States)

    Wilson, William T; McMillan, Tristan; Young, Adam M H; White, Mark A J

    2017-04-01

    Treatment-limiting decisions (TLDs) are employed to actively withhold treatment from patients whom clinicians feel would derive no benefit or suffer detrimental effects from further intervention. The use of such decisions has been heavily discussed in the media and clinicians in the past have been reluctant to institute them, even though it is in the best interests of the patients. Their use is influenced by several ethical, religious and social factors all of which have changed significantly over time. This study reports the trends in use of TLDs in a regional neurosurgical unit over 23 years. Patient archives were reviewed to identify the number of admissions and procedures performed at the Institute of Neurological Sciences, Glasgow, in the years 1988, 1997 and 2011. Death certificate records were used to identify mortality in the unit in the year 2011. Patient records were used to obtain details of diagnosis, time from admission to death, and the presence and timing of a TLD. The results show an increase in the use of TLDs, with decisions made for 89% of those who died in 2011, compared to 68% in 1997 and 51% in 1988. The number of admissions has increased substantially since 1988 as has the percentage of patients undergoing surgery (46, 67 and 72% in 1988, 1997 and 2011, respectively). There is a trending increase in the number of patients who have a TLD in our regional neurosurgical unit. This demonstrates an increased willingness of clinicians to recognise poor prognosis and to withdraw or withhold treatment in these cases. Continued appropriate use of the TLD is recommended but it is to only ever reflect the best interests of the patient.

  8. Antiretroviral treatment reduces increased CSF neurofilament protein (NFL) in HIV-1 infection.

    Science.gov (United States)

    Mellgren, A; Price, R W; Hagberg, L; Rosengren, L; Brew, B J; Gisslén, M

    2007-10-09

    Increased levels of the light-chain neurofilament protein (NFL) in CSF provide a marker of CNS injury in several neurodegenerative disorders and have been reported in the AIDS dementia complex (ADC). We examined the effects of highly active antiretroviral treatment (HAART) on CSF NFL in HIV-1-infected subjects with and without ADC who underwent repeated lumbar punctures (LPs). NFL was measured by ELISA (normal reference value NFL at baseline, with a median level of 780 ng/L and an intraquartile range (IQR) of 480 to 7300. After 3 months of treatment, NFL concentrations had fallen to normal in 48% (10/21), and the median decreased to 340 ng/L (IQR NFL levels. Thirty-two subjects had normal NFL at baseline, and all but one remained normal at follow-up. These effects on CSF NFL were seen in association with clinical improvement in ADC patients, decreases in plasma and CSF HIV-1 RNA and CSF neopterin, and increases in blood CD4 T cell counts. HAART seems to halt the neurodegenerative process(es) caused by HIV-1, as shown by the significant decrease in CSF NFL after treatment initiation. CSF NFL may serve as a useful marker in monitoring CNS injury in HIV-1 infection and in evaluating CNS efficacy of antiretroviral therapy.

  9. Increased incidence of liver cancer after successful DAA treatment of chronic hepatitis C: Fact or fiction?

    Science.gov (United States)

    Alberti, Alfredo; Piovesan, Sara

    2017-06-01

    Therapy of hepatitis C has been revolutionized by Direct Antiviral Agents. These drugs are safe and efficacious in all infected patients, including those with advanced, or decompensated cirrhosis, and are currently largely used in such cases in clinical practice worldwide. It was therefore cause of great concern the publication of two reports suggesting that treatment with DAAs could increase the risk of hepatocellular carcinoma in cirrhotic patients, particularly in those receiving antiviral therapy after having been cured for an HCC. These reports have generated a great and controversial debate and have been followed by a series of other publications not confirming such increased risk. This article summarizes published studies assessing the relation between DAA therapy and HCC in two different clinical setting: HCC recurrence in patients with an history of cured HCC and "de novo" HCC occurrence in patients without previous HCC. Rates of HCC recurrence after DAAs were extremely variable in different studies, reflecting great heterogeneity of this clinical setting. Data on "de novo" HCC incidence were more homogeneous and suggest that treatment with DAAs is not modifying the risk of developing HCC in the first 6-12 months. The possibility that treatment with DAAs may favour tumour growth and spread in individual patients with active HCC foci is suggested by some observations but remains unproven. There is clearly a need for prospective studies designed to better define these issues. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Conductive Gel Increases the Small Tumor Treatment With Electrochemotherapy Using Needle Electrodes.

    Science.gov (United States)

    Suzuki, Daniela O H; Marques, Claudia M G; Rangel, Marcelo M M

    2016-07-01

    The combination of chemotherapy drugs and high electric field treatment in local cancer is named electrochemotherapy. The European Standard Operation Procedure of Electrochemotherapy (ESOPE) provides guidelines for treatment of cutaneous and subcutaneous tumors. The electrochemotherapy of numerous tumors varying in sizes is more convenient using needle electrodes. However, ESOPE recommends that needle electrodes are applied to deeper tumors. The application of needle electrodes to treatment of superficial small tumors seems to be practical in electrochemotherapy. Plate electrodes and gel improve the electrochemotherapy efficacy. This technique provides electric field homogeneity in irregularly shaped tissue structures (bulk tumors). We propose an investigation of needle electrode and gel in electrochemotherapy of superficial tumors. In vivo experiment with squamous cell carcinoma (SCC) spontaneous nodules in dog was used to validate the mathematical tissue model. The numerical model considers the tissue conductivity dependent on local electric field. Our studies demonstrated that conductive gel is important for effective treatment of superficial tumors with needle electrodes. The needle electrodes and gel presented reduction of medium current, increased the tumor-free margin, and improved the practical application in relation to plate electrode.

  11. Fluoxetine increases suicide ideation less than placebo during treatment of adults with minor depressive disorder.

    Science.gov (United States)

    Garlow, Steven J; Kinkead, Becky; Thase, Michael E; Judd, Lewis L; Rush, A John; Yonkers, Kimberly A; Kupfer, David J; Frank, Ellen; Schettler, Pamela J; Rapaport, Mark Hyman

    2013-09-01

    Some reports suggest an increase in suicide ideations and behaviors in patients treated with antidepressants. This is an analysis of the impact of fluoxetine on suicide ideations in outpatients with minor depressive disorder. Research subjects were adult outpatients with minor depressive disorder (N = 162), who received fluoxetine or placebo in a prospective, 12-week, double-blind randomized trial. The research participants were evaluated weekly with standard rating scales that included four suicide-related items: item 3 of the Hamilton Rating Scale for Depression (HRSD), item 18 of Inventory of Depressive Symptomatology (IDS-C), and items 15 and 59 of the Hopkins Symptom Checklist (SCL-90). Clinically significant intensification of suicide ideation was defined as an increase of ≥2 points on any of these items. Overall 60/162 subjects (37%) had an increase of ≥1 point during treatment and 17/162 (10.5%) of ≥2 points on at least one suicide item, with 12/81 (14.8%) placebo and 5/81 (6.2%) fluoxetine-treated subjects having a ≥2 point gain. Of the study participants with baseline suicide ideation, 9/22 (40.9%) placebo and 3/24 (12.5%) fluoxetine treated had ≥2 point increase (p = 0.04). Survival analysis revealed that subjects on placebo were significantly more likely (p = 0.050) to experience a ≥2 point increase on one or more item, a difference that emerged early and continued throughout the 12-week trial. Compared to placebo, fluoxetine was not associated with a clinically significant increase in suicide ideation among adults with minor depressive disorder during 12 weeks of treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Formulation and evaluation of bilayer tablet by using melt granulation technique for treatment of diabetes mellitus.

    Science.gov (United States)

    Patel, Dhruvita; Patel, Ankita; Solanki, Trupti

    2012-03-01

    The objective of present study was to prepare and characterize Bilayer tablet formulation containing Metformin HCl in extended release matrix form and Pioglitazone HCl in immediate release form for the treatment of diabetes mellitus. Different formulations containing Metformin HCl were manufactured using 3(2) factorial designs. Influence of hydrophilic carrier, hydrophobic polymer on drug release was studied. Immediate release layer of Pioglitazone was optimized using different super disintegrants. All formulations were evaluated for percentage drug release. Optimization results indicated that release rate of Metformin is directly proportional to the levels of Eudragit S 100 and PEG 6000. Results confirmed that Bilayer tablet formulation containing extended release of Metformin HCl and immediate release of Pioglitazone HCl could be developed by using melt granulation technique.

  13. Pre-sowing magnetic treatments of tomato seeds increase the growth and yield of plants.

    Science.gov (United States)

    De Souza, A; Garcí, D; Sueiro, L; Gilart, F; Porras, E; Licea, L

    2006-05-01

    The effects of pre-sowing magnetic treatments on growth and yield of tomato (cv Campbell-28) were investigated under field conditions. Tomato seeds were exposed to full-wave rectified sinusoidal non-uniform magnetic fields (MFs) induced by an electromagnet at 100 mT (rms) for 10 min and at 170 mT (rms) for 3 min. Non-treated seeds were considered as controls. Plants were grown in experimental plots (30.2 m(2)) and were cultivated according to standard agricultural practices. During the vegetative and generative growth stages, samples were collected at regular intervals for growth rate analyses, and the resistance of plants to geminivirus and early blight was evaluated. At physiological maturity, the plants were harvested from each plot and the yield and yield parameters were determined. In the vegetative stage, the treatments led to a significant increase in leaf area, leaf dry weight, and specific leaf area (SLA) per plant. Also, the leaf, stem, and root relative growth rates of plants derived from magnetically treated seeds were greater than those shown by the control plants. In the generative stage, leaf area per plant and relative growth rates of fruits from plants from magnetically exposed seeds were greater than those of the control plant fruits. At fruit maturity stage, all magnetic treatments increased significantly (P magnetically treated seeds than that of the controls. A significant delay in the appearance of first symptoms of geminivirus and early blight and a reduced infection rate of early blight were observed in the plants from exposed seeds to MFs. Pre-sowing magnetic treatments would enhance the growth and yield of tomato crop.

  14. Short-term nutritional treatments grazing legumes or feeding concentrates increase prolificacy in Corriedale ewes.

    Science.gov (United States)

    Viñoles, C; Meikle, A; Martin, G B

    2009-07-01

    We tested whether short periods of increased nutrition will improve ovulation rate and prolificacy, irrespective of the method used to synchronise the cycles of the ewes. In Experiment 1, we used 138 Corriedale ewes to evaluate two factors: synchronization treatment (sponges versus a single injection of prostaglandin) and type of pasture (native versus improved with Lotus corniculatus). Ewes were mated at the end of the grazing period and prolificacy was evaluated at lambing. Grazing Lotus corniculatus for 12 days tended to increase the number of twin lambs born (P=0.09). The percentage of ewes showing oestrus during a 9-day period was similar among synchronization treatments. Animals in Experiments 2 (n=282) and 3 (n=288) were allocated to a control group or a group fed a supplement of corn grain and soybean meal for 7 days. Ewes received 2 prostaglandin injections and the supplement was fed from Days 11 to 17 after the second prostaglandin. Ovulation rate was measured in 65 (Experiment 2) and 61 (Experiment 3) ewes that were confirmed to have consumed the supplement and showed oestrus in a 4-day period. The supplement increased ovulation rate by 14% in both experiments (PLotus corniculatus and in ovulation rate to 7 days feeding with a supplement rich in energy and protein. Moreover, in these studies, prostaglandin was as effective as sponges for synchronising oestrus, an important factor in future decisions about hormonal management of fertility.

  15. Bladder catheterization increases susceptibility to infection that can be prevented by prophylactic antibiotic treatment

    Science.gov (United States)

    Rousseau, Matthieu; Goh, H.M. Sharon; Holec, Sarah; Albert, Matthew L.; Williams, Rohan B.H.; Ingersoll, Molly A.; Kline, Kimberly A.

    2016-01-01

    Catheter-associated urinary tract infections (CAUTI) are the most common hospital-associated infections. Here, we report that bladder catheterization initiated a persistent sterile inflammatory reaction within minutes of catheter implantation. Catheterization resulted in increased expression of genes associated with defense responses and cellular migration, with ensuing rapid and sustained innate immune cell infiltration into the bladder. Catheterization also resulted in hypersensitivity to Enterococcus faecalis and uropathogenic Escherichia coli (UPEC) infection, in which colonization was achieved using an inoculum 100-fold lower than the ID90 for infection of an undamaged urothelium with the same uropathogens. As the time of catheterization increased, however, colonization by the Gram-positive uropathogen E. faecalis was reduced, whereas catheterization created a sustained window of vulnerability to infection for Gram-negative UPEC over time. As CAUTI contributes to poorer patient outcomes and increased health care expenditures, we tested whether a single prophylactic antibiotic treatment, concurrent with catheterization, would prevent infection. We observed that antibiotic treatment protected against UPEC and E. faecalis bladder and catheter colonization as late as 6 hours after implantation. Thus, our study has revealed a simple, safe, and immediately employable intervention, with the potential to decrease one of the most costly hospital-incurred infections, thereby improving patient and health care economic outcome. PMID:27699248

  16. Increased vertical dimension of occlusion: signs, symptoms, diagnosis, treatment and options.

    Science.gov (United States)

    Discacciati, José Augusto César; Lemos de Souza, Eduardo; Vasconcellos, Walison Arthuso; Costa, Sérgio Carvalho; Barros, Vinícius de Magalhães

    2013-01-01

    During the planning of oral rehabilitation, the vertical dimension of occlusion (VDO) is one of the first parameters to be measured since its improper restoration can lead to the failure of any prosthetic rehabilitation. A decreased VDO can lead to the appearance of lesions, such as angular cheilitis, facial disharmony, and temporomandibular disorders; meanwhile, an increased VDO may lead to the onset of joint and muscle pain, tension in functional speech, difficulty in swallowing, impaired chewing, tooth sensitivity due to traumatogenic forces, pathologic bone resorption, abnormal wearing of teeth, the appearance of an elongated face, and a facial expression of fatigue. Most scientific articles deal with methods and techniques for re-establishing VDO in edentulous patients or those who have lost their tooth reference due to prosthetic preparations. However, patients with increased VDO are also found in everyday practice. One treatment option for these patients is occlusal adjustment by selective tooth wear; it is still possible to perform orthodontic intrusion and/or orthognathic surgery in severe cases. The aim of this study was to discuss signs, symptoms, diagnosis, and treatment, and to report a clinical case of a patient with increased VDO.

  17. Treatment of Arabidopsis thaliana seeds with an HSP90 inhibitor increases plant resistance

    Science.gov (United States)

    Kozeko, Liudmyla

    2016-07-01

    Resistance of plants to unfavourable conditions is an important feature to use them as an autotrophic link of Life Support Systems in space exploration missions. It significantly depends on basic and stress-induced levels of heat shock proteins (HSP) in cells. It is known that HSP90 can bind and maintain heat shock transcription factors (HSF) as a monomer that lacks DNA binding activity and thereby regulate HSP expression. Modulation of activity of the HSP synthesis and resistance by HSP90 in plants is not well investigated. The objective of this study was to determine how treatment of seeds with an HSP90 inhibitor affects environmental responsiveness in Arabidopsis thaliana. Seed treatment with geldanamycin (GDA) was used to reduce HSP90 function. The affect of space flight stressors was simulated by gamma-irradiation and thermal upshift. Two series of experiments were carried out: 1) exposure of dry seeds to gamma-irradiation (1 kGy, ^{60}Co); 2) heat shock of seedlings. It was shown that GDA treatment of seeds stimulated the seedling growth after seed irradiation. It also increased both the basic thermotolerance (45°C for 45 min) and induced thermotolerance (45°C for 1,5-2,5 h after pretreatment at 37°C for 2 h) in seedlings. In addition, seed treatment with GDA had a prolonged effect on the HSP70 production in seedlings under normal and stressful conditions. It shows that the stimulatory effects of GDA may be caused by induction of HSP70 synthesis. The obtained data demonstrate that pre-treatment of seeds with GDA before planting allows inducing the stress resistance at least at early growth stages of plants.

  18. Acute Stimulant Treatment and Reinforcement Increase the Speed of Information Accumulation in Children with ADHD.

    Science.gov (United States)

    Fosco, Whitney D; White, Corey N; Hawk, Larry W

    2016-10-27

    The current studies utilized drift diffusion modeling (DDM) to examine how reinforcement and stimulant medication affect cognitive task performance in children with ADHD. In Study 1, children with (n = 25; 88 % male) and without ADHD (n = 33; 82 % male) completed a 2-choice discrimination task at baseline (100 trials) and again a week later under alternating reinforcement and no-reinforcement contingencies (400 trials total). In Study 2, participants with ADHD (n = 29; 72 % male) completed a double-blind, placebo-controlled trial of 0.3 and 0.6 mg/kg methylphenidate and completed the same task utilized in Study 1 at baseline (100 trials). Children with ADHD accumulated information at a much slower rate than controls, as evidenced by a lower drift rate. Groups were similar in nondecision time and boundary separation. Both reinforcement and stimulant medication markedly improved drift rate in children with ADHD (ds = 0.70 and 0.95 for reinforcement and methylphenidate, respectively); both treatments also reduced boundary separation (ds = 0.70 and 0.39). Reinforcement, which emphasized speeded accuracy, reduced nondecision time (d = 0.37), whereas stimulant medication increased nondecision time (d = 0.38). These studies provide initial evidence that frontline treatments for ADHD primarily impact cognitive performance in youth with ADHD by improving the speed/efficiency of information accumulation. Treatment effects on other DDM parameters may vary between treatments or interact with task parameters (number of trials, task difficulty). DDM, in conjunction with other approaches, may be helpful in clarifying the specific cognitive processes that are disrupted in ADHD, as well as the basic mechanisms that underlie the efficacy of ADHD treatments.

  19. Glycine treatment decreases proinflammatory cytokines and increases interferon-gamma in patients with type 2 diabetes.

    Science.gov (United States)

    Cruz, M; Maldonado-Bernal, C; Mondragón-Gonzalez, R; Sanchez-Barrera, R; Wacher, N H; Carvajal-Sandoval, G; Kumate, J

    2008-08-01

    Amino acids have been shown to stimulate insulin secretion and decrease glycated hemoglobin (A1C) in patients with Type 2 diabetes. In vitro, glycine reduces tumor necrosis factor (TNF)-alpha secretion and increases interleukin-10 secretion in human monocytes stimulated with lipopolysaccharide. The aim of this study was to determine whether glycine modifies the proinflammatory profiles of patients with Type 2 diabetes. Seventy-four patients, with Type 2 diabetes were enrolled in the study. The mean age was 58.5 yr, average age of diagnosis was 5 yr, the mean body mass index was 28.5 kg/m2, the mean fasting glucose level was 175.5 mg/dl and the mean A1C level was 8%. They were allocated to one of two treatments, 5 g/d glycine or 5 g/d placebo, po tid, for 3 months. A1C levels of patients given glycine were significantly lower after 3 months of treatment than those of the placebo group. A significant reduction in TNF-receptor I levels was observed in patients given glycine compared with placebo. There was a decrease of 38% in the interferon (IFN)-gamma level of the group treated with placebo, whereas that of the group treated with glycine increased up to 43%. These data showed that patients treated with glycine had a significant decrease in A1C and in proinflammatory cytokines and also an important increase of IFN-gamma. Treatment with glycine is likely to have a beneficial effect on innate and adaptive immune responses and may help prevent tissue damage caused by chronic inflammation in patients with Type 2 diabetes.

  20. Chronic SIV and morphine treatment increases heat shock protein 5 expression at the synapse.

    Science.gov (United States)

    Pendyala, Gurudutt; Periyasamy, Palsamy; Callen, Shannon; Fox, Howard S; Lisco, Steven J; Buch, Shilpa J

    2015-10-01

    The abuse of opiates such as morphine in synergy with HIV infection accelerates neurocognitive impairments and neuropathology in the CNS of HIV-infected subjects, collectively referred to as HAND. To identify potential pathogenic markers associated with HIV and morphine in perturbing the synaptic architecture, we performed quantitative mass spectrometry proteomics on purified synaptosomes isolated from the caudate of two groups of rhesus macaques chronically infected with SIV differing by one regimen-morphine treatment. The upregulation of heat shock 70-kDa protein 5 in the SIV + morphine group points to increased cellular stress during SIV/morphine interaction thus leading to CNS dysfunction.

  1. Complementary acupuncture treatment increases cerebral metabolism in patients with Parkinson's disease.

    Science.gov (United States)

    Huang, Yong; Jiang, Xuemei; Zhuo, Ying; Tang, Anwu; Wik, Gustav

    2009-01-01

    We used positron emission tomography (PET) and the 18-flourodeoxyglucose tracer to study cerebral effects of complementary acupuncture in Parkinson's disease. Five patients received scalp-acupuncture and Madopa, while the other five had Madopa only. PET scans before and after 5 weeks of complementary acupuncture treatment show increased glucose metabolisms in parietal, temporal, occipital lobes, the thalamus, and the cerebellum in the light-diseased hemisphere, and in parietal and occipital lobes of the severe-diseased hemisphere. No changes were observed in the Madopa-only group. Acupuncture in combination with Madopa may improve cerebral glucose metabolism in Parkinson's disease.

  2. Increased incidence of infertility treatment among women working in the plastics industry

    DEFF Research Database (Denmark)

    Hougaard, K.S.; Hannerz, H.; Feveile, H.

    2009-01-01

    Several plastic chemicals adversely affect reproductive ability. This study examined the possible association between employment in the plastics industry and infertility. Dynamic cohorts of economically active women and men were followed for hospital contacts due to infertility in the Danish...... infertility were observed among female plastic workers, as opposed to an expected 87.15 cases, i.e. relative risk was 1.23 (95% CI: 1.01-1.48). For male workers the numbers were 41 respectively 49.9 cases, with relative risk being 0.82 (95% CI: 0.59-1.11). The increased incidence of infertility treatment...

  3. Chronic SIV and Morphine treatment increases heat shock protein 5 expression at the synapse

    Science.gov (United States)

    Pendyala, Gurudutt; Periyasamy, Palsamy; Callen, Shannon; Fox, Howard S.; Lisco, Steven J.; Buch, Shilpa J.

    2015-01-01

    The abuse of opiates such as morphine in synergy with HIV infection accelerates neurocognitive impairments and neuropathology in the CNS of HIV infected subjects, collectively referred to as HAND. To identify potential pathogenic markers associated with HIV and morphine in perturbing the synaptic architecture, we performed quantitative mass spectrometry proteomics on purified synaptosomes isolated from the caudate of two groups of rhesus macaques chronically infected with SIV differing by one regimen- morphine treatment. The up regulation of heat shock 70 kDa protein 5 in the SIV+morphine group points to increased cellular stress during SIV/Morphine interaction thus leading to CNS dysfunction. PMID:26037114

  4. Increase in natural killer cell activity during diethylcarbamazine treatment of patients with filariasis

    DEFF Research Database (Denmark)

    Pedersen, B K; Bygbjerg, Ib Christian; Svenson, M

    1987-01-01

    Two patients, one with Bancroftian filariasis and the other with onchocerciasis, and two healthy controls were treated with diethylcarbamazine (DEC). The natural killer (NK) cell activity of the two patients increased during DEC treatment to 2.5 and 2.8 times, respectively, while...... that of the controls remained unchanged. We conclude that the augmentation of baseline NK cell activity, as well as interferon- and interleukin-2-enhanced NK cell activity seen in the patients, is not a direct effect of DEC, but is related to the reaction to DEC in lymphatic filariasis and onchocerciasis....

  5. Increase in natural killer cell activity during diethylcarbamazine treatment of patients with filariasis.

    Science.gov (United States)

    Pedersen, B K; Bygbjerg, I C; Svenson, M

    1987-09-01

    Two patients, one with Bancroftian filariasis and the other with onchocerciasis, and two healthy controls were treated with diethylcarbamazine (DEC). The natural killer (NK) cell activity of the two patients increased during DEC treatment to 2.5 and 2.8 times, respectively, while that of the controls remained unchanged. We conclude that the augmentation of baseline NK cell activity, as well as interferon- and interleukin-2-enhanced NK cell activity seen in the patients, is not a direct effect of DEC, but is related to the reaction to DEC in lymphatic filariasis and onchocerciasis.

  6. Analysis of Case Reports of Pioglitazone's Adverse Drug Reaction%吡格列酮的不良反应病例报告分析

    Institute of Scientific and Technical Information of China (English)

    曾艳; 李晓玲; 王育琴

    2011-01-01

    Objective:To review and analyze the case reports of pioglitazone' s adverse drug reactions to provide reference for rational and safe use of pioglitazone. Method: Reactions Weekly was searched for case reports with the key word ' pioglitazone' , types of ADRs of the case reports were classified and the patients' clinical characteristics, types and outcome of ADRs were analyzed. Result:41 case reports of ADRs associated with pioglitazone were found. 41 patients consisted of 21 males, 19 females and 1 unidentified, and were aged 30 -82 years with a pioglitazone' s dosage 15 -45 mg per day and its duration from 1 week to 2 years. Their ADRs were involved in many systems such as cardiovascular system, respiratory system and biliary system. Except for 1 patient with unaquired outcome, 8 patients died, the rest recovered after pioglitazone' s discontinuation with or without therapy. Conclusion: Pioglitazone could induce severe adverse reactions such as heart failure and liver failure. The medical staff should monitor ADR as they used piolitazone.%目的:对吡格列酮药品不良反应(ADR)病例报告进行回顾分析,为临床合理安全使用提供参考.方法:以"pioglitazone"为检索词检索Reactions Weekly,将检索到的ADR病例报告分类,分别提取患者的临床特征及ADR类型、转归等信息,进行统计分析.结果:检索到与吡格列酮相关ADR病例报告41份.41名患者中男21例,女19例,1名性别不明.年龄30-82岁,吡格列酮剂量15-45 mg·d-1,疗程1周-2年.发生ADR分别涉及心血管系统、呼吸系统、肝胆系统等多个系统/器官.41名患者中1名转归不明,8名死亡,其余患者停药后或停药经治疗后好转或痊愈.结论:吡格列酮引起的心衰、肝衰竭等ADR会给患者带来较大危害,甚至危及到生命.医务人员在使用吡格列酮的同时,要关注其ADR.

  7. Long-term IGF-I treatment of children with Laron syndrome increases adiposity.

    Science.gov (United States)

    Laron, Zvi; Ginsberg, Shira; Lilos, Pnina; Arbiv, Mira; Vaisman, Nahum

    2006-02-01

    Laron syndrome (LS) is an autosomal recessive disease caused by deletions or mutations in the GH receptor gene leading to an inability of insulin-like growth factor I (IGF-I) generation. Among the major resulting body changes are dwarfism and obesity. The only effective treatment is daily administration of biosynthetic IGF-I. Body composition determination by DEXA (dual energy X-ray absorptiometry) of three girls with LS treated by IGF-I for 1, 3 and 11 1/2 years, respectively, revealed that concomitantly with the increase in growth there was a significant increase in body adipose tissue to double or triple the normal values. Due to the underdevelopment of the muscular and skeletal systems body mass index (BMI) did not accurately reflect the degree of obesity. In conclusion, IGF-I similar to insulin, exerts an adipogenic effect.

  8. The potential use of genetics to increase the effectiveness of treatment programs for criminal offenders.

    Science.gov (United States)

    Beaver, Kevin M; Jackson, Dylan B; Flesher, Dillon

    2014-01-01

    During the past couple of decades, the amount of research examining the genetic underpinnings to antisocial behaviors, including crime, has exploded. Findings from this body of work have generated a great deal of information linking genetics to criminal involvement. As a partial result, there is now a considerable amount of interest in how these findings should be integrated into the criminal justice system. In the current paper, we outline the potential ways that genetic information can be used to increase the effectiveness of treatment programs designed to reduce recidivism among offenders. We conclude by drawing attention to how genetic information can be used by rehabilitation programs to increase program effectiveness, reduce offender recidivism rates, and enhance public safety.

  9. [Comparative study of the increase in acid solubility resistance of enamel using different fluoride treatments].

    Science.gov (United States)

    Rodríguez Miro, M J; Gallego Rodríguez, J; Elías Avila, L; Albuerne Dihigo, R; Alfonso Laguárdia, D

    1988-01-01

    This investigation was performed to evaluate, comparatively, the effect of topical application of Duraphat, Flulak, Fluor-Protector, Bifluorid 12, Profilac, Fluoro-gel-P and Fluocal-gel. Colorimetric technique was used for such purposes. It was found that 67.5% of 283 children treated with those different treatments increased their enamel resistance to acid dissolution, although notable differences were found in the use of these products. Average of increase ranged between 10.7 and 23.5%. Lacs and varnishes provide best results than gels with regard to acid dissolution rate of enamel. Behave of the two national products evaluated (Flulak and Profilac) was similar to the rest of lacs and varnishes, justifying their use at national level for the prevention of caries, avoiding in that way unnecessary importations.

  10. Arsenic treatment increase Aurora-A overexpression through E2F1 activation in bladder cells.

    Science.gov (United States)

    Kao, Yu-Ting; Wu, Chin-Han; Wu, Shan-Ying; Lan, Sheng-Hui; Liu, Hsiao-Sheng; Tseng, Ya-Shih

    2017-04-18

    Arsenic is a widely distributed metalloid compound that has biphasic effects on cultured cells. In large doses, arsenic can be toxic enough to trigger cell death. In smaller amounts, non-toxic doses may promote cell proliferation and induces carcinogenesis. Aberration of chromosome is frequently detected in epithelial cells and lymphocytes of individuals from arsenic contaminated areas. Overexpression of Aurora-A, a mitotic kinase, results in chromosomal instability and cell transformation. We have reported that low concentration (≦1 μM) of arsenic treatment increases Aurora-A expression in immortalized bladder urothelial E7 cells. However, how arsenic induces carcinogenesis through Aurora-A activation remaining unclear. Bromodeoxyuridine (BrdU) staining, MTT assay, and flow cytometry assay were conducted to determine cell proliferation. Messenger RNA and protein expression levels of Aurora-A were detected by reverse transcriptional-PCR and Western blotting, respectively. Centrosome of cells was observed by immunofluorescent staining. The transcription factor of Aurora-A was investigated by promoter activity, chromosome immunoprecipitation (ChIP), and small interfering RNA (shRNA) assays. Mouse model was utilized to confirm the relationship between arsenic and Aurora-A. We reveal that low dosage of arsenic treatment increased cell proliferation is associated with accumulated cell population at S phase. We also detected increased Aurora-A expression at mRNA and protein levels in immortalized bladder urothelial E7 cells exposed to low doses of arsenic. Arsenic-treated cells displayed increased multiple centrosome which is resulted from overexpressed Aurora-A. Furthermore, the transcription factor, E2F1, is responsible for Aurora-A overexpression after arsenic treatment. We further disclosed that Aurora-A expression and cell proliferation were increased in bladder and uterus tissues of the BALB/c mice after long-term arsenic (1 mg/L) exposure for 2 months. We

  11. Calorie control increased vaspin levels of serum and periepididymal adipose tissue in diet-induced obese rats in association with serum free fatty acid and tumor necrosis factor alpha

    Institute of Scientific and Technical Information of China (English)

    WANG You-min; WANG Wen-ping; WANG Li-ping; L(U) Qi-huan; ZHOU Xiao-hui

    2010-01-01

    Background Vaspin was recently identified as a novel adipokine that is predominantly secreted from adipose tissue and exerts insulin-sensitizing effects. This study was undertaken to elucidate the regulative effects of calorie control on the expression of vaspin and its potential mechanism.Methods Diet-induced obese Sprague Dawley (SD) rats were adopted as experimental models and accepted interventions of various ingestions and pioglitazone. Various differentiated stages of cultured 3T3-L1 cells were dealt with pioglitazone or TNFα in vitro for 48 hours to further verify findings in animal experiments.Results The rats were successfully induced into an obese experimental model with hyperinsulinemia, hyperlipidemia, and increased serum free fatty acid and TNFa by 12-week high-fat diet. It was found that depending on whether the rats were fed by a high-fat diet or a basal diet, there was extremely higher vaspin in the periepididymal fat pad than in subcutaneous adipose tissues by 16 weeks. Vaspin in sera and the periepididymal fat pad was much lower in rats with a high-fat diet than those with a basal diet (all P <0.05), but vaspin in subcutaneous fat tissues was prone to increase in rats with a high-fat diet. A 4-week calorie restriction or pioglitazone on the obese rats resulted in a partial recovery of vaspin levels in sera and periepididymal adipose tissues, especially the latter revealed a more obvious superiority and increased vaspin levels of subcutaneous adipose. Surprisingly, the treatment of 4-week high-fat diet on non-obese rats did not significantly depress vaspin of sera and periepididymal adipose tissues. However, it is unknown if re-feeding generated the effect on vaspin levels of obese and non-obese rats on sera or adipose tissues. The correlation analysis showed that vaspin levels of serum and periepididymal fat tissues were negatively correlated with serum FFA, TNFα and insulin; meanwhile, there was a positive correlation between serum vaspin and

  12. The learning curve of laparoscopic treatment of rectal cancer does not increase morbidity.

    Science.gov (United States)

    Luján, Juan; Gonzalez, Antonio; Abrisqueta, Jesús; Hernandez, Quiteria; Valero, Graciela; Abellán, Israel; Frutos, María Dolores; Parrilla, Pascual

    2014-01-01

    The treatment of rectal cancer via laparoscopy is controversial due to its technical complexity. Several randomized prospective studies have demonstrated clear advantages for the patient with similar oncological results to those of open surgery, although during the learning of this surgical technique there may be an increase in complications and a worse prognosis. Our aim is to analyze how the learning curve for rectal cancer via laparoscopy influences intra- and postoperative results and oncological markers. A retrospective review was conducted of the first 120 patients undergoing laparoscopic surgery for rectal neoplasia. The operations were performed by the same surgical team with a wide experience in the treatment of open colorectal cancer and qualified to perform advanced laparoscopic surgery. We analyzed sex, ASA, tumour location, neoadjuvant treatment, surgical technique, operating time, conversion, postoperative complications, length of hospital stay, number of lymph nodes, stage and involvement of margins. Significant differences were observed with regard to surgical time (224 min in the first group, 204 min in the second group), with a higher rate of conversion in the first group (22.5%) than in the second (11.3%). No significant differences were noted for rate of conservative sphincter surgery, length of hospital stay, post-surgical complications, number of affected/isolated lymph nodes or affected circumferential and distal margins. It is possible to learn this complex surgical technique without compromising the patient's safety and oncological outcome. Copyright © 2013 AEC. Published by Elsevier Espana. All rights reserved.

  13. [Increasing number of teenagers with alcohol intoxication admitted to hospital: result of successful treatment approach rather than an increasing problem].

    Science.gov (United States)

    Lemmens, Paul

    2012-01-01

    Admissions of adolescents with acute alcohol intoxication to Dutch hospitals have been increasing since 2003. This trend has been attributed mainly to changes in drinking practices of adolescents. However, research shows a declining trend in binge drinking among Dutch teenagers. It is argued that the rise in admissions is primarily the result of a successful intervention initiated around 2003 by the Dutch Paediatric Surveillance Centre (NSCK), which has raised awareness of the problems related to underage drinking and has led the public to call for medical attention for a comatose youngster more rapidly. The rhetorical presentation of adolescent drinking as a growing problem runs the risk of inflating this problem, with moral antecedents, not uncommon when professionals deal with behaviour-related health issues. Rather than blaming the problematic drinker, the positive effects of this innovative approach should be emphasized.

  14. Hydrogel increases localized transport regions and skin permeability during low frequency ultrasound treatment

    Science.gov (United States)

    Pereira, Tatiana Aparecida; Ramos, Danielle Nishida; Lopez, Renata F. V.

    2017-01-01

    Low frequency ultrasound (LFU) enhances skin permeability via the formation of heterogeneous localized transport regions (LTRs). In this work, hydrogels with different zeta potentials were used as the coupling medium for LFU to investigate their contribution to LTR patterns and to the skin penetration of two model drugs, calcein and doxorubicin (DOX). When hydrogels were used, LTRs covering at least a 3-fold greater skin area were observed compared to those resulting from traditional LFU treatment and sodium lauryl sulfate. More LTRs resulted in an enhancement of calcein skin permeation. The zeta potential of the hydrogels affected the skin penetration of the positively charged DOX; the cationic coupling medium decreased the DOX recovered from the viable epidermis by 2.8-fold, whereas the anionic coupling medium increased the DOX accumulation in the stratum corneum by 4.4-fold. Therefore, LFU/hydrogel treatment increases LTRs areas and can target ionized drugs to specific skin layers depending on the zeta potential of the coupling medium. PMID:28287146

  15. Increasing complexity: which drug class to choose for treatment of hypertension in the elderly?

    Directory of Open Access Journals (Sweden)

    Kaiser EA

    2014-03-01

    Full Text Available Edelgard Anna Kaiser,1 Ulrich Lotze,2 Hans Hendrik Schäfer1,31Roche Diagnostics International AG, Rotkreuz, Switzerland; 2Department of Internal Medicine, DRK-Manniske-Krankenhaus Bad Frankenhausen, Bad Frankenhausen, Germany; 3Institute of Anatomy II, University Hospital Jena, Friedrich-Schiller University, Jena, GermanyAbstract: Treatment of hypertension in the elderly is expected to become more complex in the coming decades. Based on the current landscape of clinical trials, guideline recommendations remain inconclusive. The present review discusses the latest evidence derived from studies available in 2013 and investigates optimal blood pressure (BP and preferred treatment substances. Three common archetypes are discussed that hamper the treatment of hypertension in the very elderly. In addition, this paper presents the current recommendations of the NICE 2011, JNC7 2013-update, ESH/ESC 2013, CHEP 2013, JNC8 and ASH/ISH guidelines for elderly patients. Advantages of the six main substance classes, namely diuretics, beta-blockers (BBs, calcium channel blockers (CCBs, angiotensin-converting enzyme inhibitors (ACEIs, angiotensin receptor blockers (ARBs, and direct renin inhibitors (DRIs are discussed. Medical and economic implications of drug administration in the very elderly are presented. Avoidance of treatment-related adverse effects has become increasingly relevant. Current substance classes are equally effective, with similar effects on cardiovascular outcomes. Selection of substances should therefore also be based on collateral advantages of drugs that extend beyond BP reduction. The combination of ACEIs and diuretics appears to be favorable in managing systolic/diastolic hypertension. Diuretics are a preferred and cheap combination drug, and the combination with CCBs is recommended for patients with isolated systolic hypertension. ACEIs and CCBs are favorable for patients with dementia, while CCBs and ARBs imply substantial cost

  16. Evaluation of medical treatments to increase survival of ebullism in guinea pigs

    Science.gov (United States)

    Stegmann, Barbara J.; Pilmanis, Andrew A.; Wolf, E. G.; Derion, Toniann; Fanton, J. W.; Davis, H.; Kemper, G. B.; Scoggins, Terrell E.

    1993-01-01

    Spaceflight carriers run a constant risk of exposure to vacuum. Above 63,000 ft (47 mmHg), the ambient pressure falls below the vapor pressure of water at 37 C, and tissue vaporization (ebullism) begins. Little is know about appropriate resuscitative protocols after such an ebullism exposure. This study identified injury patterns and mortality rates associated with ebullism while verifying effectiveness of traditional pulmonary resuscitative techniques. Male Hartley guinea pigs were exposed to 87,000 ft for periods of 40 to 115 sec. After descent, those animals that did not breathe spontaneously were given artificial ventilation by bag and mask for up to 15 minutes. Those animals surviving were randomly assigned to one of three treatment groups--hyperbaric oxygen (HBO), ground-level oxygen (GLO2), and ground-level air (GLAIR). The HBO group was treated on a standard treatment table 6A while the GLO2 animals received O2 for an equivalent length of time. Those animals in the GLAIR group were observed only. All surviving animals were humanely sacrified at 48 hours. Inflation of the animal's lungs after the exposure was found to be difficult and, at times, impossible. This may be due to surfactant disruption at the alveolar lining. Electron microscopy identified a disruption of the surfactant layer in animals that did not survive initial exposure. Mortality was found to increase with exposure time: 40 sec--0 percent; 60 sec--6 percent; 70 sec--40 percent; 80 sec--13 percent; 100 sec--38 percent; 110 sec--40 percent; and 115 sec--100 percent. There was no difference in the delayed mortality among the treatment groups (HBO--15 percent, GLO2--11 percent, GLAIR--11 percent). However, since resuscitation was ineffective, the effectiveness of any post-exposure treatment was severely limited. Preliminary results indicate that reuscitation of guinea pigs following ebullism exposure is difficult, and that current techniques (such as traditional CPR) may not be appropriate.

  17. 吡格列酮对非酒精性脂肪性肝病大鼠血小板源生长因子-B和基质金属蛋白酶抑制因子-2表达的影响%Effect of Pioglitazone on expression of PDGB-B and TIMP-2 in rats with non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    杨志宏; 孔令亭; 于传亭

    2012-01-01

    administration from the beginning of the eighth week. All the rats were sacrificed at the 20th week. The expression levels of PDGF-B and TIMP-2 were assayed by immunohistological chemistry. Results; ①Hepatic tissue pathological change: there were obvious steatosis in model group and the Pioglitazone group, and steato-sis in model group was significantly more serious. Inflammatory reaction was common in the livers of model group, but were seldom seen in normol group. Although some inflammatory cell and cellular necrosis were seen in Pioglitazone group, the severity were more lighter than in model group. ②Expression character of TIMP-2 in the normal group, model group and Pioglitazone group, dye index were 1. 22 ±0. 31, 4.52 ±0. 61, 1. 89 ±0.45, the expression of PDGF-B were (0.82 ±0. 13) , (3. 79 ± 0.32), (0.91 ±0.27) μm2, there was statistical significance in the normal group and model group (P<0.05) . The expression of TIMP-2 and PDGF-B remarkably decreased in Pioglitazone group than those of the model group (P<0. 05) . Conclusion; PDGF-B and TIMP-2 are increased in steatosis model animals. Pioglitazone not only can decrease levels of serum lipid, but also decrease the expression of liver TIMP-2 and PDGF-B. Pioglitazone not only can improve steatosis, but also delay or/and blocked the development from NASH to liver fibrosis. Perhaps, improved TIMP-2 and PDGF-B level is one of the main mechanism of TZDs protection effect. Pioglitazone can improve NAFLD not only by improve insulin resistance but also anti-inflammatory, antifibrosis.

  18. Bed rest and increased diuretic treatment in chronic congestive heart failure

    DEFF Research Database (Denmark)

    Abildgaard, U; Aldershvile, J; Ring-Larsen, H

    1985-01-01

    To elucidate the effect of bed rest used as an adjunct to increased diuretic treatment, twelve patients with chronic congestive heart failure (CHF) had a 50% increase in loop diuretic dosage and were allocated to either continuous bed rest or bed rest during nights only. The 24-hour bed rest group...... reduced their weight significantly (mean +/- SEM: 2.00 +/- 0.79 kg, P less than 0.001), whereas the night bed rest group had no significant weight reduction (1.10 +/- 0.37 kg, 0.1 less than P less than 0.2) during three days of observation. Furthermore, the 24-hour bed rest group had a significantly...... increased diuresis (P less than 0.05) during the first day of the study and a tendency towards increased natriuresis. The cumulated diuresis for the two groups (24-hour bed rest versus night bed rest) during the three days of study were 7773 +/- 700 ml and 5861 +/- 909 ml (0.05 less than P less than 0...

  19. Salicylic Acid Treatment Increases the Levels of Triterpene Glycosides in Black Cohosh (Actaea Racemosa) Rhizomes.

    Science.gov (United States)

    De Capite, Annette; Lancaster, Tyler; Puthoff, David

    2016-01-01

    Black cohosh (Actaea racemosa) serves as the host plant for the Appalachian azure butterfly, Celastrina neglectamajor. Overharvesting of Black cohosh for the dietary supplement industry may result in its extirpation, and may also cause the elimination of the dependent butterfly. One way to increase or maintain the number of host plants in forested environments would be to reduce the number harvested, for example by increasing the levels of the desired metabolites in Black cohosh rhizomes. The secondary metabolites actein and deoxyactein are triterpene glycosides and are among the compounds associated with the putative activity of Black cohosh extracts. Acetein and deoxyacetein are used to standardize Black cohosh supplements. To gain an understanding of mechanisms that may control actein and deoxyactein accumulation, Black cohosh rhizomes were treated with exogenous salicylic acid, jasmonic acid, or ethylene, or were mechanically wounded. Salicylic acid treatment significantly increased the levels of actein and deoxyactein in the rhizome of Black cohosh, suggesting that the synthesis of triterpene glycosides is controlled in part by salicylic acid. Using salicylic acid or related chemicals to increase the levels of actein and deoxyactein in rhizomes may help supply the supplement industry and, simultaneously, help conserve Black cohosh and species dependent upon it.

  20. 吡格列酮对2型糖尿病患者护骨素和骨密度的影响%Effects of pioglitazone on the osteoprotegrin and bone mineral density in patients with type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    吴玉洁; 邢学农; 陈若平; 陈超; 陈燕; 任安; 叶山东

    2009-01-01

    Objective To investigate the effects of pioglitazone on the osteoprotegrin (OPG) and bone mineral density (BMD) in the patients with type 2 diabetes mellitus.Methods Fifty-seven patients with T2DM were randomly divided into control group (24 cases) and experimental group (33 cases),with thirty people as normal control group.In addition to the basement therapy of blood sugar control,the experimental group received pioglitazone (30 mg/day) for three months.BMD and OPG levels were measured and compared between before and after treatment.Results ① OPG level of T2DM was higher than that of normal control (P0.05).③ Hip and lumbar spine BMD of T2DM experimental group decreased after pioglitazone treatment.Conclusions Adverse effects of pioglitazone on bone metabolism might surpass the favorable factors.%目的 探讨噻唑烷二酮类药物吡格列酮对2型糖尿病(T2DM)患者护骨素和骨密度的影响.方法 57例T2DM患者,随机分为T2DM对照组24例,T2DM实验组33例,实验组降糖方案中联合吡格列酮(30 mg/d),疗程3个月;正常对照30例.治疗前后分别测定糖尿病患者和健康对照组骨密度、血清护骨素(OPG)水平,并进行比较.结果 ①T2DM血清护骨素(OPG)水平高于健康对照组(P0.05),T2DM对照组治疗前后OPG无显著变化; ③T2DM实验组经吡格列酮治疗后髋部及腰椎BMD均有所下降,而T2DM对照组治疗前后髋部及腰椎BMD无显著变化.结论 吡格列酮可对2型糖尿病患者骨代谢的不利影响因素可能超过有利因素.

  1. Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone

    OpenAIRE

    Forst, T; Guthrie, R.; Goldenberg, R; Yee, J.; Vijapurkar, U; Meininger, G; Stein, P.

    2014-01-01

    Aim The efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, was evaluated in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and pioglitazone. Methods In this randomized, double-blind, phase 3 study, patients (N = 342) received canagliflozin 100 or 300 mg during a 26-week, placebo-controlled, core period and a 26-week, active-controlled extension in which placebo-treated patients were switched to sitagliptin 100 mg. Efficacy ...

  2. Repetitive hyperbaric oxygen treatment increases insulin sensitivity in diabetes patients with acute intracerebral hemorrhage

    Science.gov (United States)

    Xu, Qian; Wei, Yi-ting; Fan, Shuang-bo; Wang, Liang; Zhou, Xiao-ping

    2017-01-01

    Aim The role of hyperbaric oxygen therapy (HBOT) in the treatment of acute ischemic stroke is controversial. This study aims to investigate whether the peripheral insulin sensitivity of type 2 diabetes patients suffering from intracerebral hemorrhage can be increased after HBOT. Methods Fifty-two type 2 diabetes participants were recruited after being diagnosed with intracerebral hemorrhage in our hospital. Insulin sensitivity was measured by the glucose infusion rate during a hyperinsulinemic euglycemic clamp (80 mU m−2 min−1) at baseline and 10 and 30 days after HBOT sessions. Serum insulin, fasting glucose, and hemoglobin A1C were measured in fasting serum at baseline and after HBOT sessions. In addition, early (∼10 days after onset) and late (1 month after onset) outcomes (National Institutes of Health Stroke Scale, NIHSS scores) and efficacy (changes of NIHSS scores) of HBOT were evaluated. Results In response to HBOT, the glucose infusion rate was increased by 37.8%±5.76% at 1 month after onset compared with baseline. Reduced serum insulin, fasting glucose, and hemoglobin A1C were observed after HBOT. Both early and late outcomes of the HBOT group were improved compared with baseline (P<0.001). In the control group, there was significant difference only in the late outcome (P<0.05). In the assessment of efficacy, there were statistically significant differences between the groups when comparing changes in NIHSS scores at 10 days and 1 month after onset (P<0.05). Conclusion Peripheral insulin sensitivity was increased following HBOT in type 2 diabetes patients with intracerebral hemorrhage. The HBOT used in this study may be effective for diabetes patients with acute stroke and is a safe and harmless adjunctive treatment. PMID:28228657

  3. Physical-chemical pretreatment as an option for increased sustainability of municipal wastewater treatment plants.

    NARCIS (Netherlands)

    Mels, A.R.

    2001-01-01

    Keywords : municipal wastewater treatment, physical-chemical pretreatment, chemically enhanced primary treatment, organic polymers, environmental sustainabilityMost of the currently applied municipal wastewater treatment plants in The Netherlands are based on the activated sludge process and include

  4. Antiretroviral treatment is associated with increased attentional load-dependent brain activation in HIV patients.

    Science.gov (United States)

    Chang, L; Yakupov, R; Nakama, H; Stokes, B; Ernst, T

    2008-06-01

    The purpose of this paper was to determine whether antiretroviral medications, especially the nucleoside analogue reverse transcriptase inhibitors, lead to altered brain activation due to their potential neurotoxic effects in patients with human immunodeficiency virus (HIV) infection. Forty-two right-handed men were enrolled in three groups: seronegative controls (SN, n = 18), HIV subjects treated with antiretroviral medications (HIV+ARV, n = 12), or not treated with antiretroviral medications (HIV+NARV, n = 12). Each subject performed a set of visual attention tasks with increasing difficulty or load (tracking two, three or four balls) during functional magnetic resonance imaging. HIV subjects, both groups combined, showed greater load-dependent increases in brain activation in the right frontal regions compared to SN (p-corrected = 0.006). HIV+ARV additionally showed greater load-dependent increases in activation compared to SN in bilateral superior frontal regions (p-corrected = 0.032) and a lower percent accuracy on the performance of the most difficult task (tracking four balls). Region of interest analyses further demonstrated that SN showed load-dependent decreases (with repeated trials despite increasing difficulty), while HIV subjects showed load-dependent increases in activation with the more difficult tasks, especially those on ARVs. These findings suggest that chronic ARV treatments may lead to greater requirement of the attentional network reserve and hence less efficient usage of the network and less practice effects in these HIV patients. As the brain has a limited reserve capacity, exhausting the reserve capacity in HIV+ARV would lead to declined performance with more difficult tasks that require more attention.

  5. Does IMRT increase the peripheral radiation dose? A comparison of treatment plans 2000 and 2010

    Energy Technology Data Exchange (ETDEWEB)

    Salz, Henning; Eichner, Regina; Wiezorek, Tilo [Jena Univ. (Germany). Dept. of Radiation Oncology

    2012-07-01

    It has been reported in several papers and textbooks that IMRT treatments increase the peripheral dose in comparison with non-IMRT fields. But in clinical practice not only open fields have been used in the pre-IMRT era, but also fields with physical wedges or composed fields. The aim of this work is to test the hypothesis of increased peripheral dose when IMRT is used compared to standard conformal radiotherapy. Furthermore, the importance of the measured dose differences in clinical practice is discussed and compared with other new technologies for the cases where an increase of the peripheral dose was observed. For cancers of the head and neck, the cervix, the rectum and for the brain irradiation due to acute leukaemia, one to four plans have been calculated with IMRT or conformal standard technique (non-IMRT). In an anthropomorphic phantom the dose at a distance of 30 cm in cranio-caudal direction from the target edge was measured with TLDs using a linear accelerator Oncor {sup registered} (Siemens) for both techniques. IMRT was performed using step-and-shoot technique (7 to 11 beams), non-IMRT plans with different techniques. The results depended on the site of irradiation. For head and neck cancers IMRT resulted in an increase of 0.05 - 0.09% of the prescribed total dose (Dptv) or 40 - 70 mGy (Dptv = 65 Gy), compared to non-IMRT technique without wedges or a decrease of 0.16% (approx. 100 mGy) of the prescribed total dose compared to non-IMRT techniques with wedges. For the cervical cancer IMRT resulted in an increased dose in the periphery (+ 0.07% - 0.15% of Dptv or 30 - 70 mGy at Dptv = 45 Gy), for the rectal cancer in a dose reduction (0.21 - 0.26% of Dptv or 100 - 130 mGy at Dptv = 50 Gy) and for the brain irradiation in an increase dose (+ 0.05% of Dptv = 18 Gy or 9 mSv). In summary IMRT does not uniformly cause increased radiation dose in the periphery in the model used. It can be stated that these dose values are smaller than reported in earlier

  6. Kinetic assay shows that increasing red cell volume could be a treatment for sickle cell disease

    Science.gov (United States)

    Li, Quan; Henry, Eric R.; Hofrichter, James; Smith, Jeffrey F.; Cellmer, Troy; Dunkelberger, Emily B.; Metaferia, Belhu B.; Jones-Straehle, Stacy; Boutom, Sarah; Christoph, Garrott W.; Wakefield, Terri H.; Link, Mary E.; Staton, Dwayne; Vass, Erica R.; Miller, Jeffery L.; Hsieh, Matthew M.; Tisdale, John F.; Eaton, William A.

    2017-01-01

    Although it has been known for more than 60 years that the cause of sickle cell disease is polymerization of a hemoglobin mutant, hydroxyurea is the only drug approved for treatment by the US Food and Drug Administration. This drug, however, is only partially successful, and the discovery of additional drugs that inhibit fiber formation has been hampered by the lack of a sensitive and quantitative cellular assay. Here, we describe such a method in a 96-well plate format that is based on laser-induced polymerization in sickle trait cells and robust, automated image analysis to detect the precise time at which fibers distort (“sickle”) the cells. With this kinetic method, we show that small increases in cell volume to reduce the hemoglobin concentration can result in therapeutic increases in the delay time prior to fiber formation. We also show that, of the two drugs (AES103 and GBT440) in clinical trials that inhibit polymerization by increasing oxygen affinity, one of them (GBT440) also inhibits sickling in the absence of oxygen by two additional mechanisms. PMID:28096387

  7. Increased plasma malondialdehyde and ffuctosamine in anemic H pylori infected patients: Effect of treatment

    Institute of Scientific and Technical Information of China (English)

    G Vijayan; RC Sundaram; Zachariah Bobby; Abdoul Hamide; N Selvaraj; N Rattina Dasse

    2007-01-01

    AIM: To unravel the possible association of malondialdehyde (MDA) and fructosamine in anemic H pylori infected patients and to observe the alteration in MDA and fructosamine levels in these patients after treatment for one month.METHODS: Fructosamine, MDA and glucose were estimated in 22 anemic H pylori infected patients and 16 healthy controls. Hematological parameters were also evaluated in both the groups using Sysmex-K-100 automated cell counter. The H pylori infected patients were randomly divided into two groups. H pylori infected patients in Group Ⅰ received both iron supplementation and anti-H pylori therapy, while patients in Group Ⅱ received only iron supplementation. All the biochemical and hematological parameters were estimated after one month of treatment.RESULTS: In anemic H pylori infected patients, while MDA (5.41 ± 2.16 vs 2.26 ± 0.50; P < 0.05) and fructosamine (2.64 ± 0.93 vs 1.60 ± 0.35; P < 0.05)were significantly increased, iron (32.72 ± 14.93 vs 110.25 ± 26.58; P < 0.05), hemoglobin (6.9 ± 2.6 vs 12.66 ± 0.74; P < 0.05) and ferritin (28.82 ± 16.27vs 140.43 ± 30.72; P < 0.05) levels were significantly decreased compared with the controls. With partial correlation analysis, fructosamine was found to have a significant positive correlation with MDA. In Group Ⅰ,while MDA level decreased significantly (3.11 ± 1.73 vs 5.50 ± 2.46; P < 0.05), there was a significant increase in iron (84.09 ± 29.51 vs 36.09 ± 17.81; P < 0.05),hemoglobin (10.40 ± 1.11 vs 7.42 ± 1.90; P < 0.05)and ferritin (116.91 ± 63.34 vs 30.46 ± 17.81; P < 0.05)levels after one month. There was no significant change in the levels of fructosamine in group Ⅰ after treatment.Similarly, no significant alterations were noted in the levels of MDA, fructosamine, hemoglobin or ferritin in Group Ⅱ patients after one month of treatment.CONCLUSION: An increased level of fructosamine and MDA was found in anemic H pylori infected patients

  8. Increased plasma malondialdehyde and fructosamine in anemic H pylori infected patients: Effect of treatment

    Science.gov (United States)

    Vijayan, G; Sundaram, RC; Bobby, Zachariah; Hamide, Abdoul; Selvaraj, N; Rattina Dasse, N

    2007-01-01

    AIM: To unravel the possible association of malon-dialdehyde (MDA) and fructosamine in anemic H pylori infected patients and to observe the alteration in MDA and fructosamine levels in these patients after treatment for one month. METHODS: Fructosamine, MDA and glucose were estimated in 22 anemic H pylori infected patients and 16 healthy controls. Hematological parameters were also evaluated in both the groups using Sysmex-K-100 automated cell counter. The H pylori infected patients were randomly divided into two groups. H pylori infected patients in GroupIreceived both iron supplementation and anti-H pylori therapy, while patients in Group II received only iron supplementation. All the biochemical and hematological parameters were estimated after one month of treatment. RESULTS: In anemic H pylori infected patients, while MDA (5.41 ± 2.16 vs 2.26 ± 0.50; P < 0.05) and fructosamine (2.64 ± 0.93 vs 1.60 ± 0.35; P < 0.05) were significantly increased, iron (32.72 ± 14.93 vs 110.25 ± 26.58; P < 0.05), hemoglobin (6.9 ± 2.6 vs 12.66 ± 0.74; P < 0.05) and ferritin (28.82 ± 16.27 vs 140.43 ± 30.72; P < 0.05) levels were significantly decreased compared with the controls. With partial correlation analysis, fructosamine was found to have a significant positive correlation with MDA. In GroupI, while MDA level decreased significantly (3.11 ± 1.73 vs 5.50 ± 2.46; P < 0.05), there was a significant increase in iron (84.09 ± 29.51 vs 36.09 ± 17.81; P < 0.05), hemoglobin (10.40 ± 1.11 vs 7.42 ± 1.90; P < 0.05) and ferritin (116.91 ± 63.34 vs 30.46 ± 17.81; P < 0.05) levels after one month. There was no significant change in the levels of fructosamine in groupIafter treatment. Similarly, no significant alterations were noted in the levels of MDA, fructosamine, hemoglobin or ferritin in Group II patients after one month of treatment. CONCLUSION: An increased level of fructosamine and MDA was found in anemic H pylori infected patients. Present data supports the

  9. Effects of pioglitazone on ambulatory pulse pressure index in patients with elderly essential hypertension and impaired glucose tolerance%吡格列酮对老年原发性高血压伴糖耐量异常患者动态脉压指数的影响

    Institute of Scientific and Technical Information of China (English)

    吴艳霞; 吴婷玉; 李秀娟; 王巍; 张琼; 熊华玲; 叶红

    2013-01-01

    (HbA1c),total cholesterol (TC),triglyceride (TG),low density lipoprotein (LDL),high density lipoprotein (HDL),NT-proBNP before and after treatmentwere measured.All patients underwent ambulatory blood pressure monitoring,24 h mean pulse pressure,PPI,AASI were count.Result:Incidence of diabetes in pioglitazone group showed significant reduction compared with control group (5.9 % ∶ 15.2 %,P<0.01).After oral treatment of pioglitazone for six months,FPG,2 h PG,TC,TG,LDL and HbA1c in pioglitazone group showed significantly decreased compared with those in control group,while HDL and NT-proBNP were not significant difference in two groups. The levels of 24 h SBP,24 h PP,PPI and AASI were decreased significantly between before and after treatment in pioglitazone group,while the level of 24 h DB P was not significant difference.Conclusion:Pioglitazone treatment could improve artery vessel function and regulate lipid and glucose metabolism in patients with elder EH and IGT,at the same time it does not affect cardiac function.

  10. Increasing use of artemisinin-based combination therapy for treatment of malaria infection in Nigerian hospitals.

    Science.gov (United States)

    Igboeli, Nneka U; Ukwe, Chinwe V; Ekwunife, Obinna I

    2010-10-01

    This study aimed at describing the pattern of outpatient antimalarial drug prescribing in a secondary and a tertiary hospital, and to assess adherence to the National Antimalarial Treatment Guideline (ATG). An audit of antimalarial prescription files from the two health facilities for a period of six months in 2008 was conducted. Semi structured questionnaires were used to collect information from the doctors and pharmacists on their awareness and knowledge of the National Antimalarial Treatment Guideline. Artemisinin-based combination therapies (ACTs) were the most prescribed antimalarials. Overall, 81.4% of the total prescriptions contained ACTs, out of which 56.8% were artemetherlumefantrine. However, adherence to the drugs indicated by national guideline within the DU90% was 38.5% for the tertiary and 66.7 % for the secondary hospital. The standard practice of prescribing with generic name was still not adhered to as evidenced in the understudied hospitals. The percentage of health care providers that were aware of the ATG was 88.2% for doctors and 85.1% for pharmacists. However, 13.3% and 52.2% of doctors and pharmacists respectively could not properly list the drugs specified in the guideline. Amodiaquine was the most commonly preferred option for managing children aged 0 - 3 months with malaria infection against the indicated oral quinine. This study showed an increased use of artemisinin-based combination therapy for the treatment of uncomplicated malaria compared previous reports in Nigeria. This study also highlights the need for periodic in-service quality assurance among health professionals with monitoring of adherence to and assessment of knowledge of clinical