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Pioglitazon

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https://www.readbyqxmd.com/read/28342366/discovery-of-new-dual-ppar%C3%AE-gpr40-agonists-with-robust-antidiabetic-activity-design-synthesis-and-in-combo-drug-evaluation
#1
Sergio Hidalgo-Figueroa, Gabriel Navarrete-Vázquez, Samuel Estrada-Soto, Diana Giles-Rivas, Francisco J Alarcón-Aguilar, Ismael León-Rivera, Abraham Giacoman-Martínez, Elizabeth Miranda Pérez, Julio C Almanza-Pérez
The design of compounds 1 and 2 was based on the similar scaffold of pharmacophoric groups for PPARγ and GPR40 agonists. In order to find new compounds with improved biological activity, the current manuscript describes a new dual PPARγ-GPR40 agonist. We synthesized two compounds, which were prepared following a multistep synthetic route, and the relative mRNA expression levels of PPARγ, GLUT4, and GPR40 were quantified in cell culture, as well as insulin secretion and [Ca(2+)] intracellular levels. Compound 1 showed a 7-times increase in the mRNA expression of PPARγ, which in turn enhanced the expression levels of GLUT4 respect to control and pioglitazone...
March 22, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28340451/the-role-of-drug-drug-interactions-in-prostate-cancer-treatment-focus-on-abiraterone-acetate-prednisone-and-enzalutamide
#2
REVIEW
Marzia Del Re, Stefano Fogli, Lisa Derosa, Francesco Massari, Paul De Souza, Stefania Crucitta, Sergio Bracarda, Daniele Santini, Romano Danesi
Elderly patients with cancer may have comorbidities, each requiring additional pharmacologic treatment. Therefore, the occurrence of pharmacokinetic (PK) and pharmacodynamic (PD) interactions is very likely, and the risk of adverse reactions (ADRs), due to the narrow therapeutic window of anticancer drugs, is increased. Drug-drug interactions (DDIs) may occur in prostate cancer patients due to inhibition by abiraterone of liver cytochrome P450 (CYP)-dependent enzymes CYP2C8 and 2D6, which are involved in the metabolism of approximately 25% of all drugs, and induction by enzalutamide of CYP3A4, 2C9 and 2C19, which metabolize up to 50% of medications...
March 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28337819/pai-1-in-granulosa-cells-is-suppressed-directly-by-statin-and-indirectly-by-suppressing-tgf-%C3%AE-and-tnf-%C3%AE-in-mononuclear-cells-by-insulin-sensitizing-drugs
#3
Kaori Yamada-Nomoto, Osamu Yoshino, Ikumi Akiyama, Akira Iwase, Yosuke Ono, Tomoko Nakamura, Miyuki Harada, Akitoshi Nakashima, Tomoko Shima, Akemi Ushijima, Yutaka Osuga, Russell Jeffrey Chang, Shunichi Shimasaki, Shigeru Saito
PROBLEM: Plasminogen activator inhibitor-1 (PAI-1) is elevated in women with polycystic ovary syndrome (PCOS), but the regulation in granulosa cells (GCs) is unclear. METHOD OF STUDY: PAI-1 expression in PCOS ovaries was investigated immunohistologically. PAI-1 expressions in HGrC1, a human GC cell line, were investigated at mRNA and activity levels. The expressions of TGF-β and TNF-α in peritoneal fluid mononuclear cells (PFMCs) were measured with quantitative PCR...
March 24, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28336578/quantitative-prediction-of-cyp3a4-induction-impact-of-measured-free-and-intracellular-perpetrator-concentrations-from-human-hepatocyte-induction-studies-on-drug-drug-interaction-predictions
#4
Yongkai Sun, Paresh P Chothe, Jennifer Sager, Hong Tsao, Amanda Moore, Leena Laitinen, Niresh Hariparsad
Typically, concentration-response curves are generated based upon nominal new chemical entity (NCE) concentrations for in-vitro-to-in-vivo extrapolation of CYP3A4 induction. These data are then used to determine the induction risk of an NCE employing various modeling approaches. The limitation to this practice is that it assumes the hepatocyte culture model to be a static system. In the current study, we assessed whether correcting for; 1) changes in perpetrator concentration in the induction medium during the assay incubation period, 2) perpetrator binding to proteins in the induction medium and 3) non-specific binding of perpetrator can improve the accuracy of CYP3A4 induction predictions...
March 23, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28333739/updated-review-confirms-potential-risk-of-bladder-cancer-with-pioglitazone
#5
Diane S Aschenbrenner
No abstract text is available yet for this article.
April 2017: American Journal of Nursing
https://www.readbyqxmd.com/read/28332144/efficacy-and-safety-of-ideglira-in-participants-with-type-2-diabetes-in-india-uncontrolled-on-oral-antidiabetic-drugs-and-basal-insulin-data-from-the-dual-clinical-trial-program
#6
Kamlesh Khunti, Viswanathan Mohan, Sunil M Jain, Trine Welløv Boesgaard, Kamilla Begtrup, Bipin Sethi
INTRODUCTION: The efficacy and safety of insulin degludec/liraglutide (IDegLira) has been evaluated in the Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes (DUAL) phase 3 clinical trial program. In this post hoc analysis, we compared the efficacy and safety of IDegLira in the Indian subpopulation with the results from the global trial population of DUAL trials. The analysis includes participants uncontrolled on oral antidiabetic drugs (OADs) in DUAL I and DUAL IV and participants uncontrolled on basal insulin and OADs in DUAL II...
March 22, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28331986/renal-function-preservation-with-pioglitazone-or-with-basal-insulin-as-an-add-on-therapy-for-patients-with-type-2-diabetes-mellitus
#7
Yu-Hung Chang, Der-Wei Hwu, Dao-Ming Chang, Ling-Wang An, Chang-Hsun Hsieh, Yau-Jiunn Lee
AIMS: Clinical outcome may differ owing to the distinct pharmacological characteristics of insulin sensitizers and insulin. This study was performed to compare the metabolic and renal function changes with add-on pioglitazone treatment versus basal insulin in patients with type 2 diabetes mellitus (DM) in whom sulfonylurea and metformin regimens failed. METHODS: Patients who were consecutively managed in the diabetes comprehensive program with add-on pioglitazone or detemir/glargine treatment for at least 2 years following sulfonylurea and metformin treatment failure were included...
March 22, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28331909/evaluating-the-effect-of-insulin-sensitizers-metformin-and-pioglitazone-alone-and-in-combination-on-women-with-polycystic-ovary-syndrome-an-rct
#8
Seyed Mojtaba Sohrevardi, Fahime Nosouhi, Saeed Hossein Khalilzade, Parichehr Kafaie, Mojgan Karimi-Zarchi, Iman Halvaei, Mehdi Mohsenzadeh
BACKGROUND: Insulin resistance and hyperinsulinemia may play a role in pathogenesis of PCOS. One of the common therapeutic methods is using insulin-sensitizing drugs such as metformin and thiazolidinediones. OBJECTIVE: The purpose was to determine the effect of metformin and pioglitazone on clinical, hormonal and metabolic parameters in women with PCOS. MATERIALS AND METHODS: Eighty four women randomly received one of the following for 3 months: metformin (n=28) (500 mg three times a day), pioglitazone (30 mg daily) (n=28) and combination of both metformin and pioglitazone (n=28) (30 mg/day pioglitazone plus 500 mg metformin three times a day)...
December 2016: International Journal of Reproductive Biomedicine (Yazd, Iran)
https://www.readbyqxmd.com/read/28324038/efficacy-of-exenatide-plus-pioglitazone-versus-basal-bolus-insulin-in-t2dm-patients-with-very-high-hba1c
#9
Muhammad Abdul-Ghani, Osama Mujahid, Ayman Mujahid, Ralph A DeFronzo, Mahmoud Zirie, Amin Jayyousi
Aim: To examine the efficacy and safety of combination therapy with exenatide plus pioglitazone versus basal-bolus insulin in poorly controlled type 2 diabetic patients with very high HbA1c (HbA1c>10%) on metformin plus sulfonylurea and long duration of disease. Research Design and Methods: 101 participants in Qatar Study with very poor glycemic control (HbA1c > 10%) and long duration of diabetes (10.9 years) on maximum/near-maximum doses of sulfonylurea plus metformin were randomized to receive: (i) pioglitazone plus weekly exenatide (Combination Therapy), or (ii) basal plus prandial insulin (Insulin Therapy) to maintain HbA1c <7...
February 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323503/add-on-dpp-4-inhibitor-alogliptin-alone-or-in-combination-with-pioglitazone-improved-%C3%AE-cell-function-and-insulin-sensitivity-in-metformin-treated-pcos
#10
Mojca Jensterle, Katja Goricar, Andrej Janez
PURPOSE: Impaired β-cell function remains unaddressed in PCOS. The aim of the study was to evaluate whether dipeptidyl peptidase-4 (DPP-4) inhibitor alogliptin (ALO) alone or in combination with pioglitazone (PIO) improves β-cell function along with insulin resistance (IR) in metformin (MET) treated obese women with PCOS with persistent IR. MATERIALS AND METHODS: In 12-week randomized study, ALO 25 mg QD (n=15) or ALO 25 mg QD and PIO 30 mg QD (n=15) was added to MET 1000 mg BID in PCOS women (aged 34...
March 21, 2017: Endocrine Research
https://www.readbyqxmd.com/read/28321087/myelodysplastic-syndrome-diagnosed-on-the-occasion-of-fournier-s-gangrene
#11
Masaaki Adachi, Kimiyoshi Mitsuhashi, Hiroyuki Matsuda, Junko Watanabe, Katsuya Nakanishi
Fournier's gangrene (FG) is a fulminant infective necrotizing fasciitis, which includes the genital, perineal, and perianal regions. A 77-year-old man had previously been diagnosed as having diabetes mellitus (DM) and was treated with pioglitazone (15 mg) and miglitol (150 mg). He developed sudden perineal discomfort, fever with painful penile, and scrotal edema, subsequently leading to urinary retention. According to physical examination and CT scan results for the swollen penis and scrotum, he was diagnosed with FG...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28303056/fixed-dose-combination-of-alogliptin-pioglitazone-improves-glycemic-control-in-japanese-patients-with-type-2-diabetes-mellitus-independent-of-body-mass-index
#12
Chie Aoki, Kunihiro Suzuki, Hisamoto Kuroda, Masaaki Sagara, Masanori Shimizu, Kikuo Kasai, Yoshimasa Aso
This study investigated the effects of switching from combination therapy with either alogliptin (Alo) or pioglitazone (Pio) to fixed-dose combination therapy (FDCT) with alogliptin and pioglitazone (Alo-Pio FDCT). The usefulness and efficacy of Alo-Pio FDCT were investigated. A total of 50 outpatients with type 2 diabetes mellitus (T2DM) treated with Alo and 47 outpatients with T2DM treated with Pio were switched to Alo-Pio FDCT, and its efficacy and usefulness were evaluated. Significant improvements were observed in hemoglobinA1c (HbA1c), alanine transaminase (ALT), and γ-glutamyl transpeptidase (GGT) levels after switching to Alo-Pio FDCT for 16 weeks in both groups...
February 2017: Nagoya Journal of Medical Science
https://www.readbyqxmd.com/read/28294376/influence-of-the-pharmacokinetic-profile-on-the-plasma-glucose-lowering-effect-of-ppar%C3%AE-agonist-pioglitazone-in-wistar-fatty-rats
#13
Akihiko Goto, Yoshihiko Tagawa, Yoshiaki Kimura, Akifumi Kogame, Yuu Moriya, Nobuyuki Amano
Although the mechanism of action for peroxisome proliferator-activated receptor gamma (PPARγ) agonists has been extensively explored, the impact of the pharmacokinetic (PK) profile on the pharmacodynamic (PD) effects of PPARγ agonists has not been elucidated in detail. We evaluated the importance of the PK profile of PPARγ agonist for its PD effect based on population PK/PD analysis. Pioglitazone hydrochloride, the PPARγ agonist, was administered orally to Wistar fatty rats once a day (qd) or once every other day (q2d) as double the amount for the qd treatment...
March 11, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28292575/the-treatment-of-type-2-diabetes-mellitus-in-patients-with-chronic-kidney-disease-what-to-expect-from-new-oral-hypoglycemic-agents
#14
REVIEW
Luca Di Lullo, Michela Mangano, Claudio Ronco, Vincenzo Barbera, Antonio De Pascalis, Antonio Bellasi, Domenico Russo, Biagio Di Iorio, Mario Cozzolino
Worldwide, an estimated 200 million people have chronic kidney disease (CKD), whose most common causes include hypertension, arteriosclerosis, and diabetes. About 40% of patients with diabetes develop CKD and intensive blood glucose control through pharmacological intervention can delay CKD progression. Standard therapies for the treatment of type 2 diabetes mellitus include metformin, sulfonylureas, meglitinides, thiazolidinediones, and insulin. While these drugs have an important role in the management of type 2 diabetes, only the thiazolidinedione pioglitazone can be used across the spectrum of CKD (stages 2-5) and without dose adjustment...
March 6, 2017: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/28286124/pharmacological-evidence-for-systemic-and-peripheral-antinociceptive-activities-of-pioglitazone-in-the-rat-formalin-test-role-of-ppar%C3%AE-and-nitric-oxide
#15
Mohammad Taghi Mansouri, Bahareh Naghizadeh, Behnam Ghorbanzadeh, Hossein Rajabi, Marzieh Pashmforoush
Nitric oxide (NO) is involved in numerous physiological processes of the central and peripheral nervous system. This study aimed to evaluate the involvement of PPARγ and NO pathway in the systemic and peripheral antinociceptive effect pioglitazone (Pio) using formalin test in rats. After allocation, rats were injected with 2.5% formalin solution and the flinching behaviors were recorded for 5min (phase 1) and 15-60min (phase 2). pioglitazone was administered intraperitoneally (i.p.) at doses (10-50mg/kg) and intraplantarly (i...
March 9, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28285649/pioglitazone-induced-improvements-in-insulin-sensitivity-occur-without-concomitant-changes-in-muscle-mitochondrial-function
#16
Sudip Bajpeyi, Magdalena Pasarica, Kevin E Conley, Bradley R Newcomer, Sharon A Jubrias, Cecilia Gamboa, Kori Murray, Olga Sereda, Lauren M Sparks, Steven R Smith
AIMS: Pioglitazone (Pio) is known to improve insulin sensitivity in skeletal muscle. However, the role of Pio in skeletal muscle lipid metabolism and skeletal muscle oxidative capacity is not clear. The aim of this study was to determine the effects of chronic Pio treatment on skeletal muscle mitochondrial activity in individuals with type 2 diabetes (T2D). MATERIALS AND METHODS: Twenty-four participants with T2D (13M/11F 53.38±2.1years; BMI 36.47±1.1kg/m(2)) were randomized to either a placebo (CON, n=8) or a pioglitazone (PIO, n=16) group...
April 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28276821/current-and-future-treatment-options-in-non-alcoholic-steatohepatitis-nash
#17
Nikos Lazaridis, Emmanuel Tsochatzis
Non-alcoholic steatohepatitis (NASH) is a chronic liver disease that can progress to cirrhosis and hepatocellular carcinoma. Diagnosis of NASH requires a liver biopsy and is defined as presence of hepatic steatosis, ballooning and lobular inflammation with or without fibrosis. Although NASH is the most common cause of liver disease in the west world and among the top three indications for liver transplantation, there are no universally accepted pharmacological therapies and therapeutic advances have been slow...
April 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28276774/pharmacological-management-of-nonalcoholic-fatty-liver-disease-in-type-2-diabetes
#18
Simona Cernea, Avivit Cahn, Itamar Raz
The prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes (T2D) is high and it is associated with poor prognosis. Hepatic steatosis results as a consequence of excessive hepatic lipid accumulation which correlates with insulin resistance and lipotoxicity, with subsequent oxidative stress, inflammation, apoptosis and fibrosis. Areas covered: This article presents the main pathophysiologic mechanisms and currently available drugs evaluated for their therapeutic effects on NAFLD/nonalcoholic steatohepatitis (NASH) and drugs under development that target relevant pathogenetic pathways...
March 6, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28272773/comparative-rna-seq-transcriptome-analyses-reveal-distinct-metabolic-pathways-in-diabetic-nerve-and-kidney-disease
#19
Lucy M Hinder, Meeyoung Park, Amy E Rumora, Junguk Hur, Felix Eichinger, Subramaniam Pennathur, Matthias Kretzler, Frank C Brosius, Eva L Feldman
Treating insulin resistance with pioglitazone normalizes renal function and improves small nerve fibre function and architecture; however, it does not affect large myelinated nerve fibre function in mouse models of type 2 diabetes (T2DM), indicating that pioglitazone affects the body in a tissue-specific manner. To identify distinct molecular pathways regulating diabetic peripheral neuropathy (DPN) and nephropathy (DN), as well those affected by pioglitazone, we assessed DPN and DN gene transcript expression in control and diabetic mice with or without pioglitazone treatment...
March 8, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28270062/antidiabetic-drugs-and-the-kidney
#20
Moses Elisaf, Eleftheria Tzavela, Nikolaos Karanatsis, Vasilis Tsimichodimos
OBJECTIVE: Nephropathy is among the most common and most devastating complications of diabetes mellitus. Recent data suggest that there is a multifaceted interaction between the kidney and antidiabetic drugs. Thus, the deterioration of renal function may result in important changes in the pharmacokinetic and pharmacodynamic properties of glucose-lowering compounds. Additionally, drugs that exert their antidiabetic properties through the inhibition of proximal glucose reabsorption are now available whereas accumulating evidence suggests that some of these drugs may exert renoprotective properties that are independent of their effect on carbohydrate metabolism...
March 6, 2017: Current Pharmaceutical Design
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