MedWorm: Avandia

Development and Validation of a repharsed Phase- HPLC method for simultaneous determination of rosiglitazone and glimepiride in combined dosage forms and human plasma

Chemistry Central Journal — Thu, 26 Jan 2012 05:00:00 +0100

Conclusion: The suggested method was successfully applied for the simultaneous analysis of the studied drugs in their co-formulated tablets and human plasma. The mean percentage recoveries in AvandarylTM tablets were 100.88 +/- 1.14 and 100.31+/- 1.93 for ROS and GLM respectively. Statistical comparison of the results with those of the reference method revealed good agreement and proved that there were no significant difference in the accuracy and precision between the two methods respectively. The interference likely to be introduced from some co-administered drugs such as glibenclamide, gliclazide, metformine, pioglitazone and nateglinide was investigated. (Source: Chemistry Central Journal)

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Thiazolidinedione Response in Familial Lipodystrophy Patients with LMNA Mutations: A Case Series

Hormone and Metabolic Research — Tue, 24 Jan 2012 05:00:00 +0100

Horm Metab ResDOI: 10.1055/s-0031-1301284Type 2 familial partial lipodystrophy (FPLD2) patients show impaired glucose and lipid metabolism resulting from lipodystrophic ‘lipid pressure’ and an intrinsic defect in skeletal muscle metabolism. Since mutated lamin A may interfere with peroxisome proliferator activator gamma (PPARγ) expression, we hypothesized that PPARγ stimulation improves fat distribution and metabolic abnormalities in these patients. 5 nondiabetic FPLD2 patients were treated with rosiglitazone over 12 months. We assessed body composition, body fat distribution, and skinfold thickness/subcutaneous tissue thickness. We also determined venous glucose, insulin, and free fatty acid (FFA) concentrations, and respiratory quotient (RQ) before and during oral glucose tolerance...

The Cardiovascular Effects of Peroxisome Proliferator-activated Receptor Agonists

The American Journal of Medicine — Mon, 23 Jan 2012 23:44:59 +0100

Abstract: Although peroxisome proliferator-activated receptor agonists are prescribed to improve cardiovascular risk factors, their cardiovascular safety is controversial. We therefore reviewed the literature to identify landmark randomized controlled trials evaluating the effect of peroxisome proliferator-activated receptor gamma agonists (pioglitazone and rosiglitazone), alpha agonists (fenofibrate and gemfibrozil), and pan agonists (bezafibrate, muraglitazar, ragaglitazar, tesaglitazar, and aleglitazar) on cardiovascular outcomes. Pioglitazone may modestly reduce cardiovascular events but also may increase the risk of bladder cancer. Rosiglitazone increases the risk of myocardial infarction and has been withdrawn in European and restricted in the United States. Fibrates improve cardiov...

Ibipinabant Attenuates Beta Cell Loss and Improves Insulin Sensitivity in Male ZDF Rats Independently of its Effects on Body Weight.

Diabetes, Obesity and Metabolism — Mon, 23 Jan 2012 05:00:00 +0100

Conclusions: Ibipinabant may have weight loss‐independent anti‐diabetic effects and may have the potential to attenuate beta cell loss in a model of progressive beta cell dysfunction. (Source: Diabetes, Obesity and Metabolism)

Transcriptional regulation of methionine adenosyltransferase 2A by peroxisome proliferator‐activated receptors in rat hepatic stellate cells

Hepatology — Mon, 23 Jan 2012 05:00:00 +0100

Conclusion:We have identified PPARγ as a negative regulator of MAT2A in quiescent HSCs. A switch from quiescence to activation state abolishes this control and allows PPARβ to up‐regulate MAT2A transcription. (HEPATOLOGY 2012.) (Source: Hepatology)

Tysabri: The Model For Facing A Drug Safety Crisis

Forbes.com Healthcare News — Fri, 20 Jan 2012 22:31:38 +0100

After a decade of drug safety crises where medicines have mostly either wound up yanked (Vioxx, Zelnorm) or close to it (Avandia), today's news about the multiple sclerosis drug Tysabri is positively amazing. (Source: Forbes.com Healthcare News)

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Physiological Responses to Acute Psychological Stress Are Reduced by the PPARγ Agonist Rosiglitazone.

Endocrinology — Tue, 17 Jan 2012 05:00:00 +0100

Authors: Ryan KK, Grayson BE, Jones KR, Schneider AL, Woods SC, Seeley RJ, Herman JP, Ulrich-Lai YM Abstract Physiological reactions to psychological stress are positively associated with several important chronic conditions including cardiovascular and neurodegenerative diseases and are linked to increased mortality. As such, the identification of cellular and molecular pathways that act to reduce stress responding may represent important targets for therapeutic intervention. Here we report that acute treatment with the peroxisome-proliferator activated receptor-γ (PPARγ) agonist rosiglitazone (RSG) blunts systemic responses to acute psychological stress in rats. Rats that had previously received oral RSG for 5 d exhibited a 40% reduction in the initial heart rate response to an...

The Effects of Febuxostat on the Pharmacokinetic Parameters of Rosiglitazone, A CYP2C8 Substrate

British Journal of Clinical Pharmacology — Fri, 13 Jan 2012 23:01:13 +0100

Conclusions: Co‐administration of febuxostat had no effect on rosiglitazone or N‐desmethylrosiglitazone PK parameters, suggesting that febuxostat can be safely given with drugs metabolized through CYP2C8.© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society (Source: British Journal of Clinical Pharmacology)

A naturally occurring rexinoid, honokiol, can serve as a regulator of various retinoid x receptor heterodimers.

Biological and Pharmaceutical Bulletin — Fri, 13 Jan 2012 09:48:02 +0100

In conclusion, we have demonstrated that honokiol is a rexinoid that possesses distinct properties from bexarotene, and mainly has subsidiary roles in the activation of RXR heterodimers by potentiating the activation of RXR heterodimers by agonists for the partner NRs. PMID: 22223330 [PubMed - in process] (Source: Biological and Pharmaceutical Bulletin)

Lipopolysaccharide represses the expression of ATP-binding cassette transporter G1 and scavenger receptor class B, type I in murine macrophages

Inflammation Research — Thu, 12 Jan 2012 16:44:46 +0100

Conclusion The data suggest that inflammatory insults repress ABCG1 and SR-BI expression partly dependent on PPARγ with a minimal effect on ABCA1 expression. Content Type Journal ArticleCategory Original Research PaperPages 1-8DOI 10.1007/s00011-011-0433-3Authors Youngki Park, Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USATho X. Pham, Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USAJiyoung Lee, Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA Journal Inflammation ResearchOnline ISSN 1420-908XPrint ISSN 1023-3830 (Source: Inflammation Research)

Citrate carrier promoter is target of peroxisome proliferator-activated receptor alpha and gamma in hepatocytes and adipocytes.

The International Journal of Biochemistry and Cell Biology — Tue, 10 Jan 2012 05:00:00 +0100

Authors: Damiano F, Gnoni GV, Siculella L Abstract Citrate carrier (CiC), a mitochondrial inner membrane protein, is an essential component of the shuttle system which transports acetyl-CoA from mitochondria to the cytosol where lipogenesis occurs. CiC is regulated by SREBP-1, a transcription factor that controls the expression of several lipogenic genes. CiC is also implicated in cholesterol synthesis, glycolysis and gluconeogenesis, suggesting that besides SREBP-1 other transcription factors could modulate the expression of its gene. Here, we provide evidences demonstrating that CiC expression is regulated by peroxisome proliferator-activated receptor (PPAR) alpha and gamma in hepatocytes and adipocytes, respectively. CiC expression increased in rat BRL-3A hepatocytes treated wit...

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State Medicaid Programs Did Not Make Use Of Prior Authorization To Promote Safer Prescribing After Rosiglitazone Warning [Diabetes Drug Safety]

Health Affairs — Mon, 09 Jan 2012 05:00:00 +0100

We examined the impact of the Food and Drug Administration’s May 2007 safety warning regarding rosiglitazone (Avandia), a diabetes drug found to raise the risk of heart attacks, on the drug’s availability on state Medicaid preferred drug lists and on the prescribing of diabetes medications more generally for Medicaid beneficiaries. Nearly all state Medicaid programs covered rosiglitazone as a preferred drug, requiring no prior authorization, with minimal change after the safety warning. At the same time, the safety warning was associated with a greater-than-expected decline in rosiglitazone prescribing among states providing coverage as a preferred drug. This suggests that providers reacted to the safety warning by reducing prescriptions. However, Medicaid programs that di...

Sitagliptin increases tau phosphorylation in the hippocampus of rats with type 2 diabetes and in primary neuron cultures.

Neurobiology of Disease — Sun, 08 Jan 2012 05:00:00 +0100

Authors: Kim DH, Huh JW, Jang M, Suh JH, Kim TW, Park JS, Yoon SY Abstract Increasing evidence supports an association between Alzheimer's disease (AD) and diabetes. In this context, anti-diabetic agents such as rosiglitazone and glucagon-like peptide (GLP)-1 have been reported to reduce pathologies associated with AD, including tau hyperphosphorylation, suggesting that such agents might be used to treat AD. One such anti-diabetic agent is sitagliptin, which acts through inhibition of dipeptidyl peptidase (DPP)-IV to increase GLP-1 levels. Given this action, sitagliptin would be predicted to reduce AD pathology. Accordingly, we investigated whether sitagliptin is effective in attenuating AD pathologies, focusing on tau phosphorylation in the OLETF type 2 diabetic rat model. Unexpec...

CTRP1 Activates AMPK to Enhance Fatty Acid Oxidation [Metabolism]

Journal of Biological Chemistry — Fri, 06 Jan 2012 05:00:00 +0100

We previously described the adipokine CTRP1, which has up-regulated expression following exposure to the anti-diabetic drug rosiglitazone and increased circulating levels in adiponectin-null mice (Wong, G. W., Krawczyk, S. A., Kitidis-Mitrokostas, C., Revett, T., Gimeno, R., and Lodish, H. F. (2008) Biochem. J. 416, 161–177). Although recombinant CTRP1 lowers blood glucose in mice, its physiological function, mechanisms of action, and roles in metabolic stress remain unknown. Here, we show that circulating levels of CTRP1 are strikingly reduced in diet-induced obese mice. Overexpressing CTRP1 in transgenic mice improved insulin sensitivity and decreased high-fat diet-induced weight gain. Reduced adiposity resulted from enhanced fatty acid oxidation and energy expenditure, effects mediate...

Thiazolidinedione dependent activation of sphingosine kinase 1 causes an anti‐fibrotic effect in renal mesangial cells

British Journal of Pharmacology — Thu, 05 Jan 2012 05:00:00 +0100

Conclusions and implications: These data show that TZD‐induced SK‐1 up‐regulation results in lower amounts of CTGF, demonstrating novel facets for the anti‐fibrotic effects of this class of drugs (Source: British Journal of Pharmacology)

Rosiglitazone attenuates activation of human Tenon’s fibroblasts induced by transforming growth factor -β1

Graefe's Archive for Clinical and Experimental Ophthalmology — Wed, 04 Jan 2012 06:46:50 +0100

Conclusions Rosiglitazone can effectively attenuate activation of HTFs induced by TGF-β1 without obvious toxicity. The possible mechanism might be that rosiglitazone interferes with TGF-β/Smad signaling pathway. Content Type Journal ArticleCategory GlaucomaPages 1-8DOI 10.1007/s00417-011-1903-6Authors Fang Fan, Department of Ophthalmology, People’s Hospital of Hebei Province, Hebei, Shijiazhuang 050051, People’s Republic of ChinaYuehua Li, Department of Ophthalmology, 2nd People’s Hospital of YunNan Province, Yunnan, Kunming 650000, People’s Republic of ChinaXuanchu Duan, Department of Ophthalmology, 2nd Xiangya Hospital, Central South University, Hunan, Changsha 410011, People’s Republic of ChinaTantai Zhao, Department of Ophthalmology, 2nd Xiangya Hospi...

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Regulation of leptin receptor expression in human polarized Caco-2/15 cells.

Endocrine, Metabolic and Immune Disorders Drug Targets — Mon, 02 Jan 2012 05:00:00 +0100

CONCLUSIONS/SIGNIFICANCE: Our results suggest that (i) the expression of LEPR in Caco-2/15 cell line is not constitutive; (ii) the agents present in the apical or basolateral medium have different effects on LEPR mRNA and/or protein levels; and (iii) short and long isoforms of LEPR follow different patterns of regulation. PMID: 22214336 [PubMed - as supplied by publisher] (Source: Endocrine, Metabolic and Immune Disorders Drug Targets)

AVE8134, a novel potent PPARα agonist, improves lipid profile and glucose metabolism in dyslipidemic mice and type 2 diabetic rats.

Acta Pharmacologica Sinica — Sun, 01 Jan 2012 05:00:00 +0100

Conclusion:AVE8134 improves lipid profile and glucose metabolism in dyslipidemic mice and type 2 diabetic rats. PMID: 22212431 [PubMed - in process] (Source: Acta Pharmacologica Sinica)

Effects of brown alga, Ecklonia cava on glucose and lipid metabolism in C57BL/KsJ-db/db mice, a model of type 2 diabetes mellitus.

Food and Chemical Toxicology — Fri, 30 Dec 2011 05:00:00 +0100

Authors: Lee SH, Min KH, Han JS, Lee DH, Park DB, Jung WK, Park PJ, Jeon BT, Kim SK, Jeon YJ Abstract Recently, there has been a growing interest in alternative therapies of marine algae for diabetes. Therefore, the anti-diabetic effects of brown alga, Ecklonia cava was investigated in type 2 diabetic animal. Male C57BL/KsJ-db/db (db/db) mice were divided into control, dieckol rich extract of E. cava (AG-dieckol), or rosiglitazone (RG) groups. The blood glucose, blood glycosylated hemoglobin levels, and plasma insulin levels were significantly lower in the AG-dieckol and RG groups than in the control db/db mice group, while glucose tolerance was significantly improved in the AG-dieckol group. AG-dieckol markedly lowered plasma and hepatic lipids concentration compared to the contro...

Decreased hepatic peroxisome proliferator-activated receptor-γ contributes to increased sensitivity to endotoxin in obstructive jaundice.

World Journal of Gastroenterology : WJG — Wed, 28 Dec 2011 05:00:00 +0100

CONCLUSION: Obstructive jaundice downregulates hepatic PPAR-γ expression, which in turn may contribute to hypersensitivity towards endotoxin. PMID: 22219595 [PubMed - in process] (Source: World Journal of Gastroenterology : WJG)

Pilot Study of Rosiglitazone as an in vivo Probe of Paclitaxel Exposure

British Journal of Clinical Pharmacology — Thu, 22 Dec 2011 05:00:00 +0100

Conclusions: The correlation between the exposure of rosiglitazone and paclitaxel likely reflects mutual dependence on the activity of CYP2C8. Rosiglitazone or similar agents may have value as in vivo probes of CYP2C8 activity. (Source: British Journal of Clinical Pharmacology)

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Activation of peroxisome proliferator-activated receptor-gamma by rosiglitazone improves lipid homeostasis at the adipose tissue-liver axis in ethanol-fed mice.

American Journal of Physiology. Gastrointestinal and Liver Physiology — Thu, 15 Dec 2011 05:00:00 +0100

Authors: Sun X, Tang Y, Tan X, Li Q, Zhong W, Sun X, Jia W, McClain CJ, Zhou Z Abstract The development of alcohol-induced fatty liver is associated with a reduction of white adipose tissue (WAT). Peroxisome proliferator-activated receptor (PPAR)-γ prominently distributes in the WAT and plays a crucial role in maintaining adiposity. The present study investigated the effects of PPAR-γ activation by rosiglitazone on lipid homeostasis at the adipose tissue-liver axis. Adult C57BL/6 male mice were pair-fed liquid diet containing ethanol or isocaloric maltose dextrin for 8 weeks with or without rosiglitazone supplementation to ethanol-fed mice for the last 3 weeks. Ethanol exposure down-regulated adipose PPAR-γ gene and reduced the WAT mass in association with induction of inflammat...

Peroxisome proliferator-activated receptor gamma agonists repress epithelial sodium channel expression in the kidney.

American Journal of Physiology. Renal Physiology — Wed, 14 Dec 2011 05:00:00 +0100

Authors: Borsting E, Cheng VP, Glass CK, Vallon V, Cunard R Abstract Thiazolidinediones (TZDs), known as peroxisome proliferator-activated receptor (PPAR) agonists, are used to treat type 2 diabetes. However, about 5% of patients experience the treatment-limiting side effect of edema. Studies have implicated activation of the epithelial sodium channel (ENaC) as a cause of TZD-induced fluid retention, though there have been conflicting reports. The goal of this study was to resolve the role of PPARγ in control of ENaC isoforms in the kidney. Herein, we demonstrate in mice that rosiglitazone (RGZ), a PPARγ ligand, increases body weight and abdominal fat pad fluid content and reduces hematocrit. Seven days of RGZ decreases ENaCα and ENaCβ mRNA and ENaCγ protein expression in kidn...

Pioglitazone is a Valid Alternative to Rosiglitazone

American Journal of Cardiovascular Drugs — Tue, 13 Dec 2011 02:41:06 +0100

(Source: American Journal of Cardiovascular Drugs)

Functional analysis of pig myostatin gene promoter with some adipogenesis- and myogenesis-related factors.

Molecular and Cellular Biochemistry — Sun, 11 Dec 2011 05:00:00 +0100

Authors: Deng B, Wen J, Ding Y, Gao Q, Huang H, Ran Z, Qian Y, Peng J, Jiang S Abstract Myostatin (MSTN) is primarily expressed in muscle and plays an important role in muscle and fat development in pigs. However, there is little information about the regulation of pig MSTN. In order to elucidate whether pig MSTN could be regulated by muscle- and fat-related factors, the porcine MSTN promoter was amplified and cloned into pGL3-basic vector, and transfected into cells to analyze the transcriptional activity of promoter with muscle- and fat-related factors through Dual-luciferase reporter assays. 5'-deletion expression showed that there was a negative-regulatory region located between nucleotides -1519 and -1236 bp, and there were some positive-regulatory regions located between -12...

PP5 and Adipogenesis [Signal Transduction]

Journal of Biological Chemistry — Fri, 09 Dec 2011 05:00:00 +0100

Glucocorticoid receptor-α (GRα) and peroxisome proliferator-activated receptor-γ (PPARγ) regulate adipogenesis by controlling the balance between lipolysis and lipogenesis. Here, we show that protein phosphatase 5 (PP5), a nuclear receptor co-chaperone, reciprocally modulates the lipometabolic activities of GRα and PPARγ. Wild-type and PP5-deficient (KO) mouse embryonic fibroblast cells were used to show binding of PP5 to both GRα and PPARγ. In response to adipogenic stimuli, PP5-KO mouse embryonic fibroblast cells showed almost no lipid accumulation with reduced expression of adipogenic markers (aP2, CD36, and perilipin) and low fatty-acid synthase enzymatic activity. This was completely reversed following reintroduction of PP5. Loss of PP5 increased phosphorylation of GRα at ser...

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An alternative synthetic route for an antidiabetic drug, rosiglitazone.

Bioorganic and Medicinal Chemistry Letters — Fri, 09 Dec 2011 05:00:00 +0100

Authors: Jawale DV, Pratap UR, Mane RA Abstract A convenient and scalable four-step novel route has been developed for the synthesis of rosiglitazone (8), an antidiabetic drug. This multistep route requires 4-fluoro benzaldehyde (4), 2,4-thiazolidinedione (6) and 2-chloro pyridine (1) as key reactants and gives overall better yield of rosiglitazone. In addition, some steps have been accelerated, which leads to an overall time saving of 10h. PMID: 22200596 [PubMed - as supplied by publisher] (Source: Bioorganic and Medicinal Chemistry Letters)

The PPAR{gamma} ligand rosiglitazone attenuates hypoxia-induced endothelin signaling in vitro and in vivo

AJP: Lung Cellular and Molecular Physiology — Mon, 05 Dec 2011 05:00:00 +0100

Peroxisome proliferator-activated receptor (PPAR) activation attenuates hypoxia-induced pulmonary hypertension (PH) in mice. The current study examined the hypothesis that PPAR attenuates hypoxia-induced endothelin-1 (ET-1) signaling to mediate these therapeutic effects. To test this hypothesis, human pulmonary artery endothelial cells (HPAECs) were exposed to normoxia or hypoxia (1% O2) for 72 h and treated with or without the PPAR ligand rosiglitazone (RSG, 10 μM) during the final 24 h of exposure. HPAEC proliferation was measured with MTT assays or cell counting, and mRNA and protein levels of ET-1 signaling components were determined. To explore the role of hypoxia-activated transcription factors, selected HPAECs were treated with inhibitors of hypoxia-inducible factor (HIF)-1&alpha...

Hypoxia induces downregulation of PPAR-{gamma} in isolated pulmonary arterial smooth muscle cells and in rat lung via transforming growth factor-{beta} signaling

AJP: Lung Cellular and Molecular Physiology — Mon, 05 Dec 2011 05:00:00 +0100

This study tested the hypothesis that there is a functional interaction between TGF-β/Smad signaling pathway and PPAR- in isolated pulmonary artery small muscle cells (PASMCs) under hypoxic stress. We observed that chronic hypoxia led to a dramatic decrease of PPAR- protein expression in whole lung homogenates (rat and mouse) and hypertrophied pulmonary arteries and isolated PASMCs. Using a transgenic model of mouse with inducible overexpression of a dominant-negative mutant of TGF-β receptor type II, we demonstrated that disruption of TGF-β pathway significantly attenuated chronic hypoxia-induced downregulation of PPAR- in lung. Similarly, in isolated rat PASMCs, antagonism of TGF-β signaling with either a neutralizing antibody to TGF-β or the selective TGF-β...

Association of thiazolidinediones with liver cancer and colorectal cancer in type 2 diabetes mellitus

Hepatology — Fri, 02 Dec 2011 05:00:00 +0100

Conclusion:The use of pioglitazone and rosiglitazone is associated with a decreased liver cancer incidence in diabetic patients. The effects on occurrence of specific cancer types may be different for pioglitazone and rosiglitazone. (HEPATOLOGY 2011.) (Source: Hepatology)

Self-monitoring cuts warfarin clot risk

OnMedica Latest News — Fri, 02 Dec 2011 00:47:48 +0100

Patients who self-monitor anticoagulation treatment nearly halve clot riskRelated items from OnMedicaStatin use after stroke not linked to bleedsConsider statins for patients at risk of clotRecurrent stroke more likely at very low BPPeople at low CVD risk should not take statinsRegulators suspend Avandia over safety concerns (Source: OnMedica Latest News)

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AFC Is a Differential SPPARM [Metabolism]

Journal of Biological Chemistry — Fri, 25 Nov 2011 05:00:00 +0100

In conclusion, we describe a new approach for the identification of differential SPPARMs and have identified AFC as a novel class of PPARγ ligand with both full and partial agonist activity in vitro and in vivo. (Source: Journal of Biological Chemistry)

Rosiglitazone and Fenofibrate Additive Effects on Lipids

Clinical and Developmental Immunology — Thu, 24 Nov 2011 23:55:40 +0100

Conclusion. Rosiglitazone does not appear to modulate hypertriglyceridemia in patients with elevated triglycerides independent of glucose metabolism. (Source: Clinical and Developmental Immunology)

Rosiglitazone ameliorates the histological parameters of the dorsal root ganglion and functional assessment after sciatic nerve injury in the rat

Acta Neurochirurgica — Thu, 24 Nov 2011 17:49:57 +0100

Conclusion Rosiglitazone has an ameliorative effect on the DRG and enhances the functional recovery after SNC in rats. Content Type Journal ArticleCategory Experimental researchPages 1-8DOI 10.1007/s00701-011-1236-6Authors Ali Noorafshan, Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, IranKhatoon Shariat, Department of Developmental Biology, Jahrom Islamic Azad University, Jahrom, IranSaied Karbalay-Doust, Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, IranAmene Omidi, Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Journal Acta NeurochirurgicaOnline ISSN 0942-0940Print ISSN 0001-6268 (Source: Acta Neurochirurgica)

The insulin sensitizing effects of PPAR-γ agonist are associated to changes in adiponectin index and adiponectin receptors in Zucker fatty rats.

Regulatory Peptides — Thu, 24 Nov 2011 05:00:00 +0100

The objective of this study is to gain further insight on the effect of the insulin sensitizing agents, PPAR-γ agonists, on the distribution of the adiponectin isoforms and the adiponectin receptors, adipoR1 and adipoR2 in an animal model of obesity and insulin resistance. To achieve the objective, Zucker fatty rats were treated with pioglitazone, rosiglitazone or placebo for six weeks. At the end of the treatment, total adiponectin, adiponectin isoforms and adiponectin receptors expression were measured. In order to see the possible relation with insulin sensitivity parameters, HOMA-IR, muscle insulin-stimulated glucose transport, muscle GLUT4 and plasma free fatty acids were also measured. The two glitazones improved insulin sensitivity and both muscle insulin-stimulated glucose transpo...

Incidence of Cardiovascular Events in Which 2 Thiazolidinediones Are Used as Add-on Treatments for Type 2 Diabetes Mellitus in a Taiwanese Population.

Clinical Therapeutics — Wed, 23 Nov 2011 05:00:00 +0100

CONCLUSIONS: Our data suggested that, as an add-on treatment for diabetic patients, rosiglitazone had significantly lower HRs for MI compared with those for pioglitazone. Diabetic hypertensive patients treated with TZD were at a high risk for angina, CHF, CVA, and MI, whereas statin use increased the risk for MI, angina, and CHF. There are some potential limitations to this study owing to the analysis methodology and retrospective design. In addition, all enrolled type 2 DM patients were treated with TZD medications, but diabetes patients treated with nonpharmacologic therapy, including lifestyle modifications, were not included. PMID: 22118894 [PubMed - as supplied by publisher] (Source: Clinical Therapeutics)

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Rosiglitazone inhibits vascular KATP channels and coronary vasodilation produced by isoprenaline

British Journal of Pharmacology — Tue, 22 Nov 2011 06:47:43 +0100

CONCLUSIONS AND IMPLICATIONS These results indicate that the vascular KATP channel is one of the targets of rosiglitazone action, through which this drug may compromise coronary responses to circulating vasodilators and perhaps also to metabolic stress. (Source: British Journal of Pharmacology)

PPARγ Agonist Improves Neuronal Insulin Receptor Function in Hippocampus and Brain Mitochondria Function in Rats with Insulin Resistance Induced by Long Term High-Fat Diets.

Endocrinology — Tue, 22 Nov 2011 05:00:00 +0100

Authors: Pipatpiboon N, Pratchayasakul W, Chattipakorn N, Chattipakorn SC Abstract We previously demonstrated that a high-fat diet (HFD) consumption can cause not only peripheral insulin resistance, but also neuronal insulin resistance. Moreover, the consumption of an HFD has been shown to cause mitochondrial dysfunction in both the skeletal muscle and liver. Rosiglitazone, a peroxizome proliferator-activated receptor-γ ligand, is a drug used to treat type 2 diabetes mellitus. Recent studies suggested that rosiglitazone can improve learning and memory in both human and animal models. However, the effects of rosiglitazone on neuronal insulin resistance and brain mitochondria after the HFD consumption have not yet been investigated. Therefore, we tested the hypothesis that rosiglita...

Rosiglitazone decreases fasting plasma peptide YY3–36 in type 2 diabetic women: a possible role in weight gain?

Acta Diabetologica — Fri, 18 Nov 2011 17:35:01 +0100

This study was designed as an open-label, randomized, controlled trial of 3-month duration. Women with newly diagnosed type 2 diabetes were studied. Twenty-eight of the 55 eligible participants were randomly assigned to receive rosiglitazone (4 mg/d). Twenty-seven patients with diabetes matched for age and body mass index served as controls on diet alone. We evaluated the effects of 3 months of rosiglitazone treatment on fasting peptide YY3–36 and ghrelin levels, and anthropometric measurements. The 3-month administration of rosiglitazone reduced fasting plasma peptide YY3–36 levels by 25%, the between-group difference was statistically significant. No effect of this thiazolidinedione compound on fasting ghrelin concentrations was observed at the end of study. The ghrel...

Rosiglitazone Leaves Retail Shelves November 17Rosiglitazone Leaves Retail Shelves November 17

Medscape Today Headlines — Thu, 17 Nov 2011 15:37:25 +0100

After November 17, diabetes drugs with rosiglitazone will be available only through certified mail-order programs. Heartwire (Source: Medscape Today Headlines)

Glimepiride/rosiglitazone: Prolonged hypoglycaemia in an elderly patient, due to contaminated dietary supplements: case report

Reactions — Wed, 16 Nov 2011 21:59:42 +0100

(Source: Reactions)

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Rosiglitazone leaves retail shelves November 17

theHeart.org — Wed, 16 Nov 2011 20:00:30 +0100

After November 17, diabetes drugs with rosiglitazone will be available only through certified mail-order programs. (Source: theHeart.org)

Postnatal Rosiglitazone Administration to Neonatal Rat Pups Does Not Alter the Young Adult Metabolic Phenotype.

Neonatology — Thu, 10 Nov 2011 05:00:00 +0100

Conclusions: Treatment with RGZ in early neonatal life does not alter later developmental metabolic programming or lead to an altered metabolic phenotype in the young adult, further re-enforcing the safety of PPARγ agonists as a novel lung-protective strategy. PMID: 22076469 [PubMed - as supplied by publisher] (Source: Neonatology)

PPAR{gamma} attenuates intimal hyperplasia by inhibiting TLR4-mediated inflammation in vascular smooth muscle cells

Cardiovascular Research — Wed, 09 Nov 2011 05:00:00 +0100

Conclusion PPAR inhibits vascular smooth muscle cell proliferation and migration by suppressing TLR4-mediated inflammation and ultimately attenuates intimal hyperplasia after carotid injury. (Source: Cardiovascular Research)

Peroxisome proliferator-activated receptor α (PPARα) activation advances locomotor activity and feeding daily rhythms in mice

International Journal of Obesity — Tue, 08 Nov 2011 05:00:00 +0100

Peroxisome proliferator-activated receptor α (PPARα) activation advances locomotor activity and feeding daily rhythms in mice International Journal of Obesity advance online publication, November 8, 2011. doi:10.1038/ijo.2011.215 Authors: R Gutman, M Barnea, L Haviv, N Chapnik & O Froy (Source: International Journal of Obesity)

Glaxo Settles Cases With U.S. for $3 Billion

NYT — Sat, 05 Nov 2011 07:00:08 +0100

The settlement was the largest yet in a wave of cases brought against pharmaceutical companies for illegal marketing of drugs. (Source: NYT)

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The anti-proliferative effect of rosiglitazone on angiotensin II-induced vascular smooth muscle cell proliferation is mediated by the mTOR pathway.

Cell Biology International — Fri, 04 Nov 2011 04:00:00 +0100

In this study, we used primary cultured rat aortic VSMCs and specific antibodies for investigating the inhibitory mechanism of rosiglitazone on Ang II-induced VSMCs proliferation. We found that rosiglitazone treatment significantly inhibited Ang II-induced rat aortic VSMC proliferation in a dose-dependent manner. Western blot analysis showed that rosiglitazone significantly lowered phosphorylated ERK 1/2, Akt, mTOR, p70S6K, and 4EBP1 levels in Ang II-treated VSMCs. In addition, PPAR-g mRNA increased significantly and connective tissue growth factor (CTGF), fibronectin (Fn), and collagen III (Col III) levels decreased significantly. The present study demonstrates that the PPAR- g activator rosiglitazone can directly inhibit the pro-atherosclerotic effect of Ang II on rat aortic VSMCs. Rosig...

Meta‐analysis: pioglitazone improves liver histology and fibrosis in patients with non‐alcoholic steatohepatitis

Alimentary Pharmacology and Therapeutics — Fri, 04 Nov 2011 04:00:00 +0100

Conclusions Thiazolidinediones significantly improve ballooning degeneration, lobular inflammation, steatosis and combined necroinflammation in patients with NASH. Pioglitazone may improve fibrosis. Larger randomised, placebo‐controlled clinical trials are needed to examine the efficacy of thiazolidinediones in improving NASH fibrosis. (Source: Alimentary Pharmacology and Therapeutics)

Glaxo Settles Cases With U.S. for $3 Billion

NYT Health — Fri, 04 Nov 2011 01:59:34 +0100

The settlement was the largest yet in a wave of cases brought against pharmaceutical companies for illegal marketing of drugs. (Source: NYT Health)

GSK agrees $3bn drug settlement

FT.com - Drugs and Healthcare — Thu, 03 Nov 2011 17:39:01 +0100

The company agrees a $3bn settlement with US authorities over sales and marketing practices of drugs such as Avandia (Source: FT.com - Drugs and Healthcare)

GSK Pays Billions to Settle Avandia Marketing Case

MedPage Today Primary Care — Thu, 03 Nov 2011 17:02:57 +0100

(MedPage Today) -- GlaxoSmithKline (GSK) has agreed to pay the government $3 billion to settle a longstanding investigation into improper sales and marketing tactics, particularly around its diabetes drug rosiglitazone (Avandia). (Source: MedPage Today Primary Care)

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GlaxoSmithKline reaches agreement in principle to resolve multiple investigations with US Government

GSK news — Thu, 03 Nov 2011 07:00:00 +0100

GSKannounced that it has reached an agreement in principle with the US Government to conclude the Company’s most significant ongoing Federal government investigations, specifically: the investigation into GSK’s sales and marketing practices begun by the US Attorney’s office of Colorado in 2004 and later taken over by the US Attorney’s Office of Massachusetts; the U.S. Department of Justice’s investigation of possible inappropriate use of the nominal price exception under the Medicaid Rebate Program; and the Department of Justice’s investigation of the development and marketing of Avandia. (Source: GSK news)

Rosiglitazone Reverses Mitomycin C Resistance in Human Gastric Cancer Cells.

The American Journal of the Medical Sciences — Wed, 02 Nov 2011 04:00:00 +0100

CONCLUSIONS:: ROS reverses MMC resistance in human gastric cancer SGC7901/VCR cells by reducing expression of MDR1, Livin and P-gp and increasing apoptosis. PMID: 22052411 [PubMed - as supplied by publisher] (Source: The American Journal of the Medical Sciences)

Rosiglitazone versus rosiglitazone and metformin versus rosiglitazone and losartan in the treatment of nonalcoholic steatohepatitis in humans: A 12‐month randomized, prospective, open‐ label trial

Hepatology — Tue, 01 Nov 2011 04:00:00 +0100

Conclusions: Forty‐eight weeks of combination therapy with rosiglitazone and metformin or rosiglitazone and losartan confers no greater benefit than rosiglitazone alone with respect to histopathology. (HEPATOLOGY 2011;) (Source: Hepatology)

Rosiglitazone and pioglitazone for the treatment of Alzheimer's disease.

The Annals of Pharmacotherapy — Tue, 01 Nov 2011 04:00:00 +0100

CONCLUSIONS: Results from clinical trials and current safety data suggest that rosiglitazone should not be used for the treatment of AD. Application of results from trials evaluating pioglitazone in the treatment of AD is limited because of major trial limitations; therefore, it should not be recommended at this time. Although these drugs are not commonly used in the treatment of AD, further pharmacoepidemiologic studies are warranted before their use can be recommended. PMID: 22028424 [PubMed - in process] (Source: The Annals of Pharmacotherapy)

Comparing the effects of insulin glargine and thiazolidinediones on plasma lipids in type 2 diabetes: a patient‐level pooled analysis

Diabetes/Metabolism Research and Reviews — Tue, 01 Nov 2011 04:00:00 +0100

ConclusionsThese findings suggest that favorable effects on plasma lipid profiles should be considered among the attributes of treatment with insulin glargine as they are for TZDs. Copyright © 2002 John Wiley & Sons, Ltd. (Source: Diabetes/Metabolism Research and Reviews)

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Rosiglitazone REMS Enrollment Deadline Is Nov. 17

Clinical Endocrinology News — Tue, 01 Nov 2011 04:00:00 +0100

Physicians who want to continue to prescribe rosiglitazone must enroll in a federal safety program by Nov. 17. The Avandia-Rosiglitazone Medicines Access Program (www.avandia.com) applies to all medicines containing rosiglitazone, including Avandia, Avandamet, and Avandaryl. After Nov. 18, these products will no longer be available through retail pharmacies and will only be available by mail order through certified pharmacies participating in the federal Risk Evaluation and Mitigation Strategy (REMS) program, the Food and Drug Administration said in a statement. (Source: Clinical Endocrinology News)

Rational therapy for Diabetes: Early recognition of adverse effects and avoidance of disruptive false alarms

Diabetes/Metabolism Research and Reviews — Tue, 01 Nov 2011 04:00:00 +0100

AbstractCorresponding to the uncontrolled diabetes pandemic, significant effort has been invested in developing new therapeutic options. Nevertheless, all medicines have possible adverse effects. Recently, a trend of 'scrutinizing' novel hypoglycemic drug side effects based on scant scientific data has emerged. With recent publications highlighting possible dangers of rosiglitazone, insulin glargine, sitagliptin, exenatide and most recently, pioglitazone, it seems that all means are valid and every data base is suitable, even if specifically defined as inadequate for the purpose of data analysis. Use of such data may lead authors to draw erroneous conclusions that may be granted unwarranted impact upon publication in leading scientific journals and eventually lead patients and misinformed ...

Adulteration of herbal antidiabetic products with undeclared pharmaceuticals: a case series in Hong Kong

British Journal of Clinical Pharmacology — Mon, 31 Oct 2011 04:20:31 +0100

Conclusions Adulteration of herbal antidiabetic products with undeclared pharmaceuticals is a significant yet under‐recognized problem. Patients taking these illicit products could be at risk of potentially fatal adverse effects. It is important to educate the public to avoid taking pCMs of dubious source. Effective regulatory measures should be put in place to address the problem. (Source: British Journal of Clinical Pharmacology)

Why do anti-inflammatory therapies fail to improve insulin sensitivity?

Acta Pharmacologica Sinica — Mon, 31 Oct 2011 04:00:00 +0100

Authors: Gao ZG, Ye JP Abstract Chronic inflammation occurs in obese conditions in both humans and animals. It also contributes to the pathogenesis of type 2 diabetes (T2D) through insulin resistance, a status in which the body loses its ability to respond to insulin. Inflammation impairs insulin signaling through the functional inhibition of IRS-1 and PPARγ. Insulin sensitizers (such as rosiglitazone and pioglitazone) inhibit inflammation while improving insulin sensitivity. Therefore, anti-inflammatory agents have been suggested as a treatment strategy for insulin resistance. This strategy has been tested in laboratory studies and clinical trials for more than 10 years; however, no significant progress has been made in any of the model systems. This status has led us to re-evalu...

Design, history and results of the Thiazolidinedione Intervention with vitamin D Evaluation (TIDE) randomised controlled trial

Diabetologia — Sat, 29 Oct 2011 05:43:28 +0100

Conclusions/interpretation Uncertainty persists regarding the clinically relevant risks and benefits of TZDs and vitamin D because of the early cancellation of this comprehensive trial. Trial registration: ClinicalTrials.gov NCT00879970 Funding: The study was funded by GlaxoSmithKline. Content Type Journal ArticleCategory ArticlePages 1-10DOI 10.1007/s00125-011-2357-4Authors The TIDE Trial Investigators, c/o Z. Punthakee, Population Health Research Institute, McMaster University, 237 Barton St E., Hamilton, ON, Canada L8L 2X2 Journal DiabetologiaOnline ISSN 1432-0428Print ISSN 0012-186X (Source: Diabetologia)

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Rosiglitazone does not improve vascular function in subjects with chronic kidney disease

Nephrology Dialysis Transplantation — Fri, 28 Oct 2011 04:00:00 +0100

Conclusion. Short-term RSG therapy reduced insulin resistance, in vivo markers of inflammation and abnormal endothelial function but had no effect on arterial function and stiffness in patients with CKD. (Source: Nephrology Dialysis Transplantation)

PPAR{gamma} Inhibits Endothelial N-Glycans [Cell Biology]

Journal of Biological Chemistry — Fri, 28 Oct 2011 04:00:00 +0100

Endothelial-monocyte interactions are regulated by adhesion molecules and key in the development of vascular inflammatory disease. Peroxisome proliferator-activated receptor (PPAR) γ activation in endothelial cells is recognized to mediate anti-inflammatory effects that inhibit monocyte rolling and adhesion. Herein, evidence is provided for a novel mechanism for the anti-inflammatory effects of PPARγ ligand action that involves inhibition of proinflammatory cytokine-dependent up-regulation of endothelial N-glycans. TNFα treatment of human umbilical vein endothelial cells increased surface expression of high mannose/hybrid N-glycans. A role for these sugars in mediating THP-1 or primary human monocyte rolling and adhesion was indicated by competition studies in which addition of α-methy...

Not only accumulation, but also saturation status of intramuscular lipids is significantly affected by PPARγ activation

Acta Physiologica — Fri, 28 Oct 2011 03:11:32 +0100

Conclusion: These findings support the conclusion that not only the change in total lipid content (DAG and TAG), but also FA composition is affected by rosiglitazone in an animal model of high fat diet induced insulin resistance. (Source: Acta Physiologica)

Metabolic stress‐induced inflammation plays a major role in the development of osteoarthritis in mice

Arthritis and Rheumatism — Thu, 27 Oct 2011 04:00:00 +0100

Conclusion:HFD‐induced OA in mice is due to low grade inflammation and not mechanical overload, since no relation between body weight and OA grade was observed. Moreover, the OA process inhibited to a great extent by treatment with two drugs with anti‐inflammatory properties. The inflammatory response to a metabolic high fat challenge may predict the individual susceptibility to develop OA later in life. The use of statins or PPAR? agonists (e.g. rosiglitazone) could be a strategy to interfere in the progression of OA. (Source: Arthritis and Rheumatism)

Erratum to: Sex dimorphic actions of rosiglitazone in generalised peroxisome proliferator-activated receptor-γ (PPAR-γ)-deficient mice

Diabetologia — Tue, 18 Oct 2011 15:58:31 +0100

Content Type Journal ArticleCategory ErratumPages 1-2DOI 10.1007/s00125-011-2337-8Authors S. Z. Duan, Department of Internal Medicine, Nephrology Division, University of Michigan Medical School, Ann Arbor, MI, USAM. G. Usher, Department of Molecular and Integrative Physiology, University of Michigan Medical School, 7641 Med. Sci. II, 1150W. Med. Ctr. Dr, Ann Arbor, MI 48109-5622, USAE. L. Foley, Department of Molecular and Integrative Physiology, University of Michigan Medical School, 7641 Med. Sci. II, 1150W. Med. Ctr. Dr, Ann Arbor, MI 48109-5622, USAD. S. Milstone, Vascular Research Division, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USAF. C. Brosius, Department of Internal Medicine, Nephrology Division, University of Michigan Medic...

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AVANDAMET (Rosiglitazone Maleate And Metformin Hydrochloride) Tablet, Film Coated [GlaxoSmithKline LLC]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Tue, 18 Oct 2011 05:00:00 +0100

Updated Date: Oct 18, 2011 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

AVANDIA (Rosiglitazone Maleate) Tablet, Film Coated [GlaxoSmithKline LLC]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Tue, 18 Oct 2011 05:00:00 +0100

Updated Date: Oct 18, 2011 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

Rosiglitazone Induces Mitochondrial Biogenesis in Differentiated Murine 3T3-L1 and C3H/10T1/2 Adipocytes

Journal of Cancer Epidemiology — Sun, 16 Oct 2011 06:52:48 +0100

Growing evidence indicates that PPARγ agonists, including rosiglitazone (RSG), induce adipose mitochondrial biogenesis. By systematically analyzing mitochondrial gene expression in two common murine adipocyte models, the current study aimed to further establish the direct role of RSG and capture temporal changes in gene transcription. Microarray profiling revealed that in fully differentiated 3T3-L1 and C3H/10T1/2 adipocytes treated with RSG or DMSO vehicle for 1, 2, 4, 7, 24, and 48 hrs, RSG overwhelmingly increased mitochondrial gene transcripts time dependently. The timing of the increases was consistent with the cascade of organelle biogenesis, that is, initiated by induction of transcription factor(s), followed by increases in the biosynthesis machinery, and then by incre...

Rosiglitazone reverses increased duodenal inhibitory response in spontaneously hypertensive rats

Neurogastroenterology and Motility — Sat, 15 Oct 2011 08:46:07 +0100

Conclusions & Inferences Chronic ROSI treatment reverses increased SHR duodenal inhibitory response acting on CO and NO components. (Source: Neurogastroenterology and Motility)

Chemical constituents of Kigelia pinnata twig and their GLUT4 translocation modulatory effect in skeletal muscle cells.

Fitoterapia — Sat, 15 Oct 2011 04:00:00 +0100

Authors: Khan MF, Dixit P, Jaiswal N, Tamrakar AK, Srivastava AK, Maurya R Abstract Phytochemical investigation of the ethanolic extract of twig of Kigelia pinnata DC. afforded one new iridoid 7-hydroxy eucommiol (1), and nine known compounds (2-10). The structure of compounds was elucidated by extensive spectroscopic methods, including 1D, 2D NMR experiments and MS analysis. All these compounds were evaluated for GLUT4 translocation modulatory effect in skeletal muscle cells. Four of the tested compounds 1, 5, 6 and 7 showed significant stimulation of GLUT4 translocation to cell surface in skeletal muscle cells without any adverse effect on cell viability. Effect of these four compounds was concentration-dependent and comparable to standard drug rosiglitazone. These findings indic...

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Anti-Diabetic Effects of TongGuanWan, a Chinese Traditional Herbal Formula, in C57BL/KsJ-db/db Mice

Planta Medica — Fri, 14 Oct 2011 04:00:00 +0100

Planta MedDOI: 10.1055/s-0031-1280268AbstractIn the present study, the anti-diabetic effects of a traditional Chinese medicinal formula extract, TongGuanWan, were investigated in type 2 diabetic animals. It was orally administered to C57BL/KsJ-db/db mice once a day for 4 weeks at the doses of 62, 125, and 250 mg/kg body weight. TongGuanWan significantly lowered the blood glucose and glycosylated haemoglobin levels as well as improved the glucose tolerance in db/db mice. The serum triglyceride levels in the db/db mice were significantly decreased, whereas the high-density lipoprotein cholesterol levels were significantly increased, after treatment with this herbal formula. TongGuanWan also markedly decreased the animals' body weights compared to those of the control db/db group but did no...

AVANDARYL (Rosiglitazone Maleate And Glimepiride) Tablet, Film Coated [GlaxoSmithKline LLC]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Thu, 13 Oct 2011 05:00:00 +0100

Updated Date: Oct 13, 2011 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

AVANDAMET (Rosiglitazone Maleate And Metformin Hydrochloride) Tablet, Film Coated [GlaxoSmithKline LLC]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Thu, 13 Oct 2011 05:00:00 +0100

Updated Date: Oct 13, 2011 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

AVANDIA (Rosiglitazone Maleate) Tablet, Film Coated [GlaxoSmithKline LLC]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Thu, 13 Oct 2011 05:00:00 +0100

Updated Date: Oct 13, 2011 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

Intermittent fasting up-regulates Fsp27/Cidec gene expression in white adipose tissue

Nutrition — Thu, 13 Oct 2011 04:00:00 +0100

Conclusion: Our study demonstrates that the transcription of the Fsp27 gene in adipose tissue may be induced in response to nutritional stimuli. Furthermore, PPARγ2, C/EBPα, and insulin may be involved in the nutritional regulation of FSP27. Thus intermittent fasting, despite lower caloric intake, may promote triacylglycerol deposition in WAT by increasing the expression of genes involved in lipid storage, such as Fsp27. (Source: Nutrition)

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The Effect of Rosiglitazone on Bone Quality in a Rat Model of Insulin Resistance and Osteoporosis.

Diabetes — Wed, 12 Oct 2011 04:00:00 +0100

CONCLUSIONSRSG decreases bone quality. An unusual finding was an increase in cortical bone porosity induced by RSG, consistent with its effect on long bones of women. ALN, an inhibitor of bone resorption, enhanced mechanical strength and may provide an approach to partially counter the deleterious skeletal effects of RSG. PMID: 21998400 [PubMed - as supplied by publisher] (Source: Diabetes)

AVANDAMET (Rosiglitazone Maleate And Metformin Hydrochloride) Tablet, Film Coated [GlaxoSmithKline LLC]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Tue, 11 Oct 2011 05:00:00 +0100

Updated Date: Oct 11, 2011 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

Glucagon-like peptide analogues for type 2 diabetes mellitus.

Cochrane Database of Systematic Reviews — Tue, 11 Oct 2011 01:20:04 +0100

CONCLUSIONS: GLP-1 agonists are effective in improving glycaemic control. PMID: 21975753 [PubMed - in process] (Source: Cochrane Database of Systematic Reviews)

Rosiglitazone, a PPAR-γ agonist, inhibits VEGF secretion by peripheral blood mononuclear cells and ROS production by human leukocytes

Inflammation Research — Mon, 10 Oct 2011 15:02:34 +0100

Conclusion The results support the involvement of PKC as a direct, and/or NADPH-oxidase as an indirect, target for the action of rosiglitazone on VEGF secretion by PBMCs and ROS production in human leukocytes. Content Type Journal ArticleCategory Original Research PaperPages 1-5DOI 10.1007/s00011-011-0386-6Authors R. T. Mattos, Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, Av. Francisco Sales 1111, Santa Efigênia, Belo Horizonte-MG, 30150-220 BrazilA. A. Bosco, Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, Av. Francisco Sales 1111, Santa Efigênia, Belo Horizonte-MG, 30150-220 BrazilJ. A. Nogueira-Machado, Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, Av. Francisco Sales 1111, Santa Efigênia, Belo Horizonte-MG, ...

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Elevated circulating vaspin levels were decreased by rosiglitazone therapy in T2DM patients with poor glycemic control on metformin alone.

Cytokine — Sat, 08 Oct 2011 21:46:33 +0100

In conclusion, plasma vaspin level is higher in T2DM patients with poor glycemic control. And rosiglitazone therapy decreased plasma vaspin levels through glucose and insulin sensitivity regulation. PMID: 21802961 [PubMed - in process] (Source: Cytokine)

Long-term Effects of Pioglitazone and Rosiglitazone on LFTsLong-term Effects of Pioglitazone and Rosiglitazone on LFTs

Medscape Today Headlines — Fri, 07 Oct 2011 12:02:21 +0100

Do LFTs improve over time with thiazolidinedione therapy? The British Journal of Diabetes and Vascular Disease (Source: Medscape Today Headlines)

AVANDIA (Rosiglitazone Maleate) Tablet, Film Coated [Cardinal Health]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Fri, 07 Oct 2011 05:00:00 +0100

Updated Date: Oct 7, 2011 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

Two Thiophenes Compounds Are Partial Peroxisome Proliferator-Activated Receptor α/γ Dual Agonists.

Biological and Pharmaceutical Bulletin — Wed, 05 Oct 2011 16:55:03 +0100

Authors: Zheng Z, Yang Y, Shao H, Liu Z, Lu X, Xu Y, He X, Jiang W, Jiang Q, Zhao B, Zhang H, Li Z, Si S Abstract In our previous study, two synthetic thiophenes such as IMB-05 and IMB-15 were found as peroxisome proliferator-activated receptor gamma (PPARγ) agonists and exhibited beneficial effects on glucose tolerance of diabetic mice in vivo. In the present study, their effect on the transactivity of other nuclear receptors was further investigated. IMB-05 and IMB-15 could not only activated PPARγ but also efficiently activate PPARα in GAL4-hPPARα/γ (ligand binding domain (LBD)) chimeric receptor assay and PPAR response element (PPRE)-luc reporter gene assay with EC(50) values of 1.8-5.2 µM, whereas no activity was observed in other nuclear receptor assays. In addition, th...

A Novel Series of (S)-2,7-Substituted-1,2,3,4-tetrahydroisoquinoline-3-carboxylic Acids: Peroxisome Proliferator-Activated Receptor α/γ Dual Agonists with Protein-Tyrosine Phosphatase 1B Inhibitory Activity.

Chemical and Pharmaceutical Bulletin — Wed, 05 Oct 2011 12:10:02 +0100

In conclusion, 14c is a promising candidate for an efficacious and safe anti-diabetic drug with triple actions as a PPARα/γ dual agonist with PTP-1B inhibitory activity. PMID: 21963632 [PubMed - in process] (Source: Chemical and Pharmaceutical Bulletin)

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Rosiglitazone enhances learning, place cell activity, and synaptic plasticity in middle-aged rats.

Neurobiology of Aging — Mon, 03 Oct 2011 04:00:00 +0100

Authors: Wang BW, Hok V, Della-Chiesa A, Callaghan C, Barlow S, Tsanov M, Bechara R, Irving E, Virley DJ, Upton N, O'Mara SM Abstract As an antidiabetic agent, rosiglitazone (ROSI) binds and activates peroxisome proliferator-activator receptor gamma (PPARγ), altering the expression of genes involved in glucose uptake and disposal, ultimately affecting glucose regulation. ROSI might therefore be a potential treatment to ameliorate age-related decline in cognitive function, particularly on an insulin-resistant background, where improvements in peripheral insulin sensitivity and central nervous system (CNS) glucose utilization may facilitate recovery of cognitive function. We therefore examined the amelioration potential of ROSI for neurocognitive deficits resulting from aging in an ...

Reactivity of the aorta and mesenteric resistance arteries from the obese spontaneously hypertensive rat: effects of glitazones.

American Journal of Physiology. Heart and Circulatory Physiology — Sat, 01 Oct 2011 04:00:00 +0100

Authors: Mendizábal Y, Llorens S, Nava E Abstract The obese spontaneously hypertensive rat (SHROB) is a model of metabolic syndrome in which, to our knowledge, vascular function has never been studied. The actions of insulin sensitizers (glitazones) on vascular function have not been analyzed either. Our purpose was to characterize microvascular and macrovascular responses of the SHROB and to study the effects of glitazones on these responses. The reactivity of mesenteric resistance arteries (MRAs) and the aorta from SHROBs and control rats to cumulative concentrations of phenylephrine, ACh, and sodium nitroprusside (SNP) was myographically analyzed. Some animals were orally treated with rosiglitazone (3 mg·kg(-1)·day(-1), 3 wk), and myography was performed. Phenylephrine, ACh, ...

Activated AMPK inhibits PPAR-{alpha} and PPAR-{gamma} transcriptional activity in hepatoma cells.

American Journal of Physiology. Gastrointestinal and Liver Physiology — Sat, 01 Oct 2011 04:00:00 +0100

We examined whether the activities of these molecules were coordinately regulated. H4IIEC3 cells were transfected with PPAR-α and PPAR-γ expression plasmids and a peroxisome-proliferator-response element (PPRE) luciferase reporter plasmid. The cells were treated with PPAR agonists (WY-14,643 and rosiglitazone), AMPK activators 5-aminoimidazole-4-carboxamide riboside (AICAR) and metformin, and the AMPK inhibitor compound C. Both AICAR and metformin decreased basal and WY-14,643-stimulated PPAR-α activity; compound C increased agonist-stimulated reporter activity and partially reversed the effect of the AMPK activators. Similar effects on PPAR-γ were seen, with both AICAR and metformin inhibiting PPRE reporter activity. Compound C increased basal PPAR-γ activity and rosiglitazone-stimul...

[Effects of Chinese herbal medicine Yiqi Zengmin Formula on expression of glucose transporter 4 in skeletal muscle in type 2 diabetic rats].

Zhong xi yi jie he xue bao : Journal of Chinese Integrative Medicine. — Sat, 01 Oct 2011 04:00:00 +0100

Conclusion: YQZM formula can enhance GLUT4 translocation from the cytoplasm to the plasma membrane in skeletal muscle tissues, and displays the insulin sensitization characteristic of rosiglitazone. PMID: 22015196 [PubMed - in process] (Source: Zhong xi yi jie he xue bao : Journal of Chinese Integrative Medicine.)

Fixed dose combination diabetes medicines - usage in the Australian veteran population.

Australian Family Physician — Sat, 01 Oct 2011 04:00:00 +0100

We examined overall trends in the utilisation and proportion of patients who had been previously dispensed both, one, or none of the individual ingredient products before initiating combination products. Results Of metformin-glibenclamide initiations, 9% involved a switch from metformin and glibenclamide as separate products, while 22% had used neither metformin nor a sulfonylurea. Thirty percent of metformin-rosiglitazone initiations involved a switch from both individual products, while in 10% neither metformin nor thiazolidinedione had been dispensed. Discussion A minority of veterans started taking the combination products after being stabilised on the individual products; many had no prior history of oral hypoglycaemic use. This prescribing may lead to wastage if combination medicatio...

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Rosiglitazone and Other Bitter Pills -- poems by doctors [Extras]

The British Journal of Psychiatry — Fri, 30 Sep 2011 04:00:00 +0100

(Source: The British Journal of Psychiatry)

Med Sci Monit 2011; 17(10):BR282-289 "Rosiglitazone protects against severe hemorrhagic shock-induced organ damage in rats"

Medical Science Monitor — Thu, 29 Sep 2011 23:33:02 +0100

Conclusions: Treatment with rosiglitazone suppresses the release of serum TNF-alpha, IL-6 and MCP-1, and ameliorates HS-induced organ damage in rats. (Source: Medical Science Monitor)

A randomized, parallel group, double‐blind, multicentre study comparing the efficacy and safety of Avandamet (rosiglitazone/metformin) and metformin on long‐term glycaemic control and bone mineral density after 80 weeks of treatment in drug‐naïve type 2 diabetes mellitus patients

Diabetes, Obesity and Metabolism — Thu, 29 Sep 2011 06:56:19 +0100

Conclusion: Superior glycaemic control was achieved with AVM compared with MET monotherapy. The superior glycaemic effects were shown to be durable over 18 months of treatment. AVM was associated with a significantly reduced BMD in comparison with MET at week 80 in the lumbar spine and total hip. (Source: Diabetes, Obesity and Metabolism)

Reactivity of the aorta and mesenteric resistance arteries from the obese spontaneously hypertensive rat: effects of glitazones

AJP: Heart and Circulatory Physiology — Wed, 28 Sep 2011 04:00:00 +0100

The obese spontaneously hypertensive rat (SHROB) is a model of metabolic syndrome in which, to our knowledge, vascular function has never been studied. The actions of insulin sensitizers (glitazones) on vascular function have not been analyzed either. Our purpose was to characterize microvascular and macrovascular responses of the SHROB and to study the effects of glitazones on these responses. The reactivity of mesenteric resistance arteries (MRAs) and the aorta from SHROBs and control rats to cumulative concentrations of phenylephrine, ACh, and sodium nitroprusside (SNP) was myographically analyzed. Some animals were orally treated with rosiglitazone (3 mg·kg–1·day–1, 3 wk), and myography was performed. Phenylephrine, ACh, and SNP dose-response curves were impai...

Effects of combining simvastatin with rosiglitazone on inflammation, oxidant stress and ambulatory blood pressure in patients with the metabolic syndrome: The SIROCO study

Diabetes, Obesity and Metabolism — Wed, 28 Sep 2011 04:00:00 +0100

Conclusion: Our data demonstrate that patients with the metabolic syndrome given a statin/TZD combination manifest greater reductions in markers of vascular inflammation and oxidant stress, 24‐hour ambulatory blood pressure and increases in adiponectin as well as improved glycemic indices. (Source: Diabetes, Obesity and Metabolism)

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Fibroblasts Expressing the Thyrotropin Receptor Overarch Thyroid and Orbit in Graves' Disease.

The Journal of Clinical Endocrinology and Metabolism — Wed, 28 Sep 2011 04:00:00 +0100

Conclusions:ColI(+)CXCR4(+)TSHR(+) thyroid fibroblasts resemble orbital fibroblasts and circulating fibrocytes. CD34(+) fibrocytes appear to infiltrate both tissues in GD. Thyroid fibroblasts lose CD34 display in culture, unlike orbital fibroblasts and circulating fibrocytes. Fibrocytes and their fibroblast derivatives may participate in the pathogenesis of thyroid autoimmunity after TSHR activation. They could represent a therapeutic target for these diseases. PMID: 21956421 [PubMed - as supplied by publisher] (Source: The Journal of Clinical Endocrinology and Metabolism)

Activated AMPK inhibits PPAR-{alpha} and PPAR-{gamma} transcriptional activity in hepatoma cells

AJP: Gastrointestinal and Liver Physiology — Tue, 27 Sep 2011 04:00:00 +0100

We examined whether the activities of these molecules were coordinately regulated. H4IIEC3 cells were transfected with PPAR-α and PPAR- expression plasmids and a peroxisome-proliferator-response element (PPRE) luciferase reporter plasmid. The cells were treated with PPAR agonists (WY-14,643 and rosiglitazone), AMPK activators 5-aminoimidazole-4-carboxamide riboside (AICAR) and metformin, and the AMPK inhibitor compound C. Both AICAR and metformin decreased basal and WY-14,643-stimulated PPAR-α activity; compound C increased agonist-stimulated reporter activity and partially reversed the effect of the AMPK activators. Similar effects on PPAR- were seen, with both AICAR and metformin inhibiting PPRE reporter activity. Compound C increased basal PPAR- activity and rosiglitazone-st...

Avandia MDL Judge Denies Avandia Statute of Limitations Motion to Dismiss

Drugs.com - Pharma News — Fri, 23 Sep 2011 12:02:38 +0100

From PR Web (September 23, 2011) U.S. District Judge Cynthia M. Rufe, the presiding judge on the federal Avandia litigation cases, denied GlaxoSmithKline's Statute of Limitations Motion to Dismiss. GlaxoSmithKline (GSK), the manufacturer of Avandia,... (Source: Drugs.com - Pharma News)

Prevention and treatment of Schistosoma mansoni-induced liver fibrosis in mice

Inflammopharmacology — Fri, 23 Sep 2011 05:55:41 +0100

Abstract The present study was designed to examine the potential preventive and curative effects of curcumin, resveratrol, imatinib, rosiglitazone, losartan and bosentan (BOS) on Schistosoma mansoni-induced liver fibrosis in mice. Induction of liver fibrosis was produced in male Swiss mice by subcutaneous injection of S. mansoni cercariae per mouse. Mice were left for 28 days before starting the experiment then mice were divided into two main groups. The first group was further subdivided into experimental groups and started drug treatment at day 28 after infection and continued for 2 weeks in order to evaluate the potential preventive effects of the mentioned drugs on S. mansoni-induced liver fibrosis. The second group of mice were left for 2 weeks and then t...

Millions “wasted” on synthetic insulins, study reveals

OnMedica Latest News — Thu, 22 Sep 2011 04:00:00 +0100

NHS has spent £625m too much on synthetic insulins in a decadeRelated items from OnMedicaCaution urged over intensive glucose controlRegulators suspend Avandia over safety concernsNICE takes U-turn on dementia drugsUse pioglitazone only in selected patients, says EMA guidanceStatin use after stroke not linked to bleeds (Source: OnMedica Latest News)

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Pharmacogenetics of oral antidiabetic treatment.

Atherosclerosis — Tue, 20 Sep 2011 07:24:03 +0100

Authors: Schroner Z, Javorsky M, Kozarova M, Tkac I Abstract In the majority of patients with type 2 diabetes (T2D), oral antidiabetic drug (OAD) treatment is the first line treatment after lifestyle measures fail. Two major groups of OAD are used in clinical practice--insulin secretagogues and insulin sensitisers. Sulphonyluea (SU) derivatives are insulin secretagogues and stimulate insulin secretion by inhibiting ATP-sensitive potassium channels. Genes KCNJ11 and ABCC8 encode potassium channel proteins. KCNJ11 gene Glu23Lys polymorphism was associated with an increased risk of SU secondary failure, while Ser1369Ala polymorphism of ABCC8 gene had influence antidiabetic efficacy of SU drug gliclazide. In addition, the polymorphism of TCF7L2 gene, which has the strongest association...

Vascular smooth muscle cell-derived adiponectin: A paracrine regulator of contractile phenotype

Journal of Molecular and Cellular Cardiology — Mon, 19 Sep 2011 04:00:00 +0100

This article is part of a Special Issue entitled “Local Signaling in Myocytes”.Graphical abstract: Highlights: ► Vascular smooth muscle cells synthesize and secrete adiponectin. ► VSMC-derived adiponectin is upregulated by PPARγ agonists. ► VSMC-derived adiponectin is required for contractile protein expression. ► VSMC-derived adiponectin acts in an autocrine and paracrine fashion. (Source: Journal of Molecular and Cellular Cardiology)

The PPAR{gamma} Ligand, Rosiglitazone, Attenuates Hypoxia-Induced Endothelin Signaling In Vitro and In Vivo.

American Journal of Physiology. Lung Cellular and Molecular Physiology — Fri, 16 Sep 2011 04:00:00 +0100

Authors: Kang BY, Kleinhenz JM, Murphy TC, Hart CM Abstract PPARγ activation attenuated hypoxia-induced pulmonary hypertension (PH) in mice although the mechanisms for these effects remain to be completely defined. We hypothesized that PPARγ attenuates hypoxia-induced endothelin-1 (ET-1) signaling. Human pulmonary artery endothelial cells (HPAECs) were exposed to hypoxia (1% O(2)) or normoxia for 72 h and treated ± the PPARγ ligand, rosiglitazone (RSG, 10 μM), during the last 24 h. Selected HPAECs were treated with chetomin (HIF-1α inhibitor, 25 nM) or with caffeic acid phenethyl ester (CAPE, NF-kB inhibitor, 20 μM) for 3 h. HPAEC proliferation was measured with MTT assays or cell counting. Male C57BL/6 mice were exposed to hypoxia (10% O(2)) or normoxia (21% O(2)) for 3 wk ...

Hypoxia Induces Downregulation of PPAR{gamma} in Isolated Pulmonary Arterial Smooth Muscle Cells and in Rat Lung via Transforming Growth Factor-{beta} Signaling.

American Journal of Physiology. Lung Cellular and Molecular Physiology — Fri, 16 Sep 2011 04:00:00 +0100

This study tested the hypothesis that there is functional interaction between TGF-β/Smad signaling pathway and PPARγ in isolated pulmonary artery small muscle cells (PASMCs) under hypoxic stress. We observed that chronic hypoxic led to a dramatic decrease of PPARγ protein expression in whole lung homogenates (rat and mouse) and hypertrophied pulmonary arteries and isolated PASMCs. Using a transgenic model of mouse with inducible overexpression of a dominant negative mutant of TGF-β receptor type II, we demonstrated that disruption of TGF-β pathway significantly attenuated chronic hypoxia-induced downregulation of PPARγ in lung. Similarly, in isolated rat PASMCs, antagonism of TGF-β signaling with either a neutralizing antibody to TGF-β or the selective TGF-β receptor type I inhibi...

Glyceollin-containing fermented soybeans improve glucose homeostasis in diabetic mice

Nutrition — Thu, 15 Sep 2011 04:00:00 +0100

Conclusion: Glyceollin-containing FSG improves glucose homeostasis, partly by enhancing hepatic insulin sensitivity in type 2 diabetic mice. (Source: Nutrition)

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Cardiovascular Safety of Diabetes Drugs: The Way ForwardCardiovascular Safety of Diabetes Drugs: The Way Forward

Medscape Today Headlines — Wed, 14 Sep 2011 21:15:58 +0100

The long shadow cast by the rosiglitazone controversy, as well as newer cancer concerns with pioglitazone, exenatide, and sitagliptin, are prompting calls for a revised approach to "signal detection" as well as to the conduct and reporting of clinical trials. Heartwire (Source: Medscape Today Headlines)

Cardiovascular safety of diabetes drugs: The way forward

theHeart.org — Wed, 14 Sep 2011 14:15:31 +0100

The PPARγ agonist rosiglitazone prevents cognitive impairment by inhibiting astrocyte activation and oxidative stress following pilocarpine-induced status epilepticus

Neurological Sciences — Tue, 13 Sep 2011 15:45:42 +0100

Abstract Epilepsy is commonly associated with cognitive impairment. Astrocyte activation and oxidative stress occur following seizures, and play a role in the pathological injury of epilepsy with cognitive impairment. The peroxisome proliferator-activated receptor gamma (PPARγ) has been shown to exhibit neuroprotective and antioxidative effects in CNS diseases. Thus, we hypothesized that rosiglitazone, a PPARγ agonist, would prevent cognitive impairment by inhibiting astrocyte activation and regulating glutathione (GSH) homeostasis after status epilepticus (SE). Using a lithium pilocarpine-induced SE model, we found that rosiglitazone significantly prevented cognitive impairment induced by SE, and potently inhibited astrocyte activation with maintenance of GSH homeostasi...

Luciferin IPA-Based Higher Throughput Human Hepatocyte Screening Assays for CYP3A4 Inhibition and Induction

Journal of Biomolecular Screening — Fri, 09 Sep 2011 04:00:00 +0100

The authors report here higher throughput screening (HTS) assays for the evaluation of CYP3A4 inhibition and CYP3A4 induction in human hepatocytes using a novel CYP3A4 substrate, luciferin IPA (LIPA). Using human recombinant CYP450 isoforms, LIPA was found to be metabolized extensively by CYP3A4 but not by CYP1A2, CYP2C9, CYP2C19, CYP2D6, or CYP2E1. In the 384-well plate CYP3A4 inhibition assay, the known inhibitors 1-aminobenzotriazole, erythromycin, ketoconazole, and verapamil were found to cause extensive (maximum inhibition of >80%), dose-dependent, statistically significant inhibition of LIPA metabolism. The non-CYP3A4 inhibitors diethyldithiocarbamate, quercetin, quinidine, sulfaphenazole, ticlopidine, and tranylcypromine were found to have substantially lower (maximum inhibition ...

New Class Of Anti-Diabetic Compound Established By Scripps Research Scientists

Health News from Medical News Today — Tue, 06 Sep 2011 08:00:00 +0100

In a joint study, scientists from The Scripps Research Institute and Harvard University's Dana-Farber Cancer Institute have established a new class of anti-diabetic compound that targets a unique molecular switch. The finding paves the way for the development of anti-diabetic therapeutics with minimal adverse side effects plaguing currently available drugs such as Avandia (rosiglitazone), scheduled to be removed from pharmacy shelves this fall due to concerns about increased risk of heart attack. The new study, led by Patrick R... (Source: Health News from Medical News Today)

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Determination of bioactive markers in Cleome droserifolia using cell-based bioassays for antidiabetic activity and isolation of two novel active compounds

Phytomedicine — Mon, 05 Sep 2011 04:00:00 +0100

Abstract: The antidiabetic activities of the aqueous (AqEx) and ethanolic (AlEx) extracts of Cleome droserifolia (Forssk.) Del., were tested in cultured C2C12 skeletal muscle cells and 3T3-L1 adipocytes. An 18-h treatment with the AqEx increased basal glucose uptake by 33% [insulin equivalent (IE)=1.3±0.04] in muscle cells comparable to a 25.5% increase caused by 100nM insulin (IE=1±0.03). Fractionation of the tested AqEx yielded hexane (HxFr), chloroform (ClFr) and ethyl acetate (EtFr) fractions which exerted 38, 52 and 35% increase in the glucose uptake corresponding to an IE of 1.5±0.06, 2.0±0.04 and 1.4±0.04, respectively. Only the ClFr and EtFr accelerated the triglyceride accumulation [rosiglitazone equivalent (RE) was 0.9±0.13 and 0.63±0.12, respectively] in pre-adipocytes un...

The potential effects of anti-diabetic medications on myocardial ischemia–reperfusion injury

Basic Research in Cardiology — Sun, 04 Sep 2011 10:54:26 +0100

Abstract Heart disease and stroke account for 65% of the deaths in people with diabetes mellitus (DM). DM and hyperglycemia cause systemic inflammation, endothelial dysfunction, a hypercoagulable state with impaired fibrinolysis and increased platelet degranulation, and reduced coronary collateral blood flow. DM also interferes with myocardial protection afforded by preconditioning and postconditioning. Newer anti-diabetic agents should not only reduce serum glucose and HbA1c levels, but also improve cardiovascular outcomes. The older sulfonylurea agent, glyburide, abolishes the benefits of ischemic and pharmacologic preconditioning, but newer sulfonylurea agents, such as glimepiride, may not interfere with preconditioning. GLP-1 analogs and sitagliptin, an oral dipeptidyl...

Antidiabetic actions of a non-agonist PPARγ ligand blocking Cdk5-mediated phosphorylation

Nature — Sun, 04 Sep 2011 04:00:00 +0100

Antidiabetic actions of a non-agonist PPARγ ligand blocking Cdk5-mediated phosphorylation Nature 477, 7365 (2011). doi:10.1038/nature10383 Authors: Jang Hyun Choi, Alexander S. Banks, Theodore M. Kamenecka, Scott A. Busby, Michael J. Chalmers, Naresh Kumar, Dana S. Kuruvilla, Youseung Shin, Yuanjun He, John B. Bruning, David P. Marciano, Michael D. Cameron, Dina Laznik, Michael J. Jurczak, Stephan C. Schürer, Dušica Vidović, Gerald I. Shulman, Bruce M. Spiegelman & Patrick R. Griffin PPARγ is the functioning receptor for the thiazolidinedione (TZD) class of antidiabetes drugs including rosiglitazone and pioglitazone. These drugs are full classical agonists for this nuclear receptor, but recent data have shown that many PPARγ-base...

Early Atheroma-Derived Agonists of Peroxisome Proliferator-Activated Receptor-{gamma} Trigger Intramedial Angiogenesis in a Smooth Muscle Cell-Dependent Manner.

Circulation Research — Wed, 31 Aug 2011 23:00:00 +0100

Conclusions:We show that VEGF-A production is upregulated in medial SMCs of human atheromatous aortas and that peroxisome proliferator-activated receptor-γ agonists derived from early intimal lesions are likely to contribute to this phenotypic change. Our findings suggest that medial SMCs are central organizers of an angiogenic response initiated by the subendothelial accumulation of atherogenic lipids. PMID: 21885829 [PubMed - as supplied by publisher] (Source: Circulation Research)

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Acute rosiglitazone treatment is cardioprotective against ischemia-reperfusion injury by modulating AMPK, Akt, and JNK signaling in nondiabetic mice

AJP: Heart and Circulatory Physiology — Mon, 29 Aug 2011 23:00:00 +0100

In this study, we tested the hypothesis that acute RGZ treatment is beneficial during I/R by modulating cardioprotective signaling pathways in a nondiabetic mouse model. RGZ (1 µg/g) was injected intravenously via the tail vein 5 min before reperfusion. Myocardial infarction was significantly reduced in mice treated with RGZ compared with vehicle controls (8.7% ± 1.1% vs. 20.2% ± 2.5%, P < 0.05). Moreover, isolated hearts were subjected to 20 min of global, no-flow ischemia in an ex vivo heart perfusion system. Postischemic recovery was significantly improved with RGZ treatment administered at the onset of reperfusion compared with vehicle (P < 0.001). Immunoblot analysis data revealed that the levels of both phospho-AMP-activated protein kinase (Thr172) and phosp...

Peroxisome proliferation–associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesity

Nature Medicine — Sun, 28 Aug 2011 04:00:00 +0100

Peroxisome proliferation–associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesity Nature Medicine 17, 1121 (2011). doi:10.1038/nm.2421 Authors: Sabrina Diano, Zhong-Wu Liu, Jin Kwon Jeong, Marcelo O Dietrich, Hai-Bin Ruan, Esther Kim, Shigetomo Suyama, Kaitlin Kelly, Erika Gyengesi, Jack L Arbiser, Denise D Belsham, David A Sarruf, Michael W Schwartz, Anton M Bennett, Marya Shanabrough, Charles V Mobbs, Xiaoyong Yang, Xiao-Bing Gao & Tamas L Horvath Previous studies have proposed roles for hypothalamic reactive oxygen species (ROS) in the modulation of circuit activity of the melanocortin system. Here we show that suppression of ROS diminishes pro-opiomelanocortin (POMC) cell activation and promotes the activity of neuropep...

Achieving a clinically relevant composite outcome of an HbA1c of

Diabetes, Obesity and Metabolism — Sat, 27 Aug 2011 15:43:05 +0100

Conclusions: As assessed by the composite outcome of HbA1c <7%, no hypoglycaemia and no weight gain, liraglutide was clearly superior to the other commonly used therapies. However, the long‐term clinical impact of this observation remains to be demonstrated. (Source: Diabetes, Obesity and Metabolism)

PPARgamma rescue of the mitochondrial dysfunction in Huntington's disease.

Neurobiology of Disease — Thu, 25 Aug 2011 04:00:00 +0100

We report here that the transcript level of PPARγ was markedly downregulated in the cortex of a transgenic mouse model of HD (R6/2). Treatment of R6/2 mice with an agonist of PPARγ (thiazolidinedione, TZD) resulted in a beneficial effect on PPARγ. By reducing Htt aggregates and thereby ameliorating the recruitment of PPARγ into Htt aggregates, TZD treatment also elevated the availability of PPARγ level and subsequently normalized the expression of downstream genes (including PGC-1α and several mitochondrial genes) in the cortex. The above protective effects appeared to be exerted by a direct activation of the PPARγ agonist (rosiglitazone) because rosiglitazone protected a neuroblastoma cell line (N2A) from mHtt-evoked mitochondrial deficiency. Our results reveal that TZD and rosigli...

Rosiglitazone protects the dorsal root ganglion cells and sciatic nerve after crush in rat.

Folia Neuropathologica — Mon, 22 Aug 2011 23:16:03 +0100

Authors: Noorafshan A, Shariat K, Karbalay-Doust S, Omidi A Abstract The aim of this study was to investigate the histological changes in the dorsal root ganglion (DRG) and the sciatic nerve in rats after sciatic nerve crush (SNC) and treatment with rosiglitazone. The rats were divided into four groups, each including seven animals, and underwent the following intervention. Group I: control animals which received carboxy methyl cellulose (0.5 w/v, p.o.). Group II: sham operated animals whose skin of the posterior thigh was opened, closed and the animals received the vehicle (carboxy methyl cellulose). Group III: SNC animals; the animals received the vehicle. Group IV: SNC with rosiglitazone (5 mg/kg body weight/day) dissolved in the vehicle. On the 28th day the fifth lumbar DRG and...

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Decreased STAMP2 Expression in Association with Visceral Adipose Tissue Dysfunction.

The Journal of Clinical Endocrinology and Metabolism — Tue, 16 Aug 2011 23:00:00 +0100

Conclusions: Decreased STAMP2 expression (mRNA and protein) might reflect visceral adipose dysfunction in subjects with obesity and type 2 diabetes. PMID: 21849520 [PubMed - as supplied by publisher] (Source: The Journal of Clinical Endocrinology and Metabolism)

Review: Rosiglitazone increases risk for cardiovascular outcomes and mortality compared with pioglitazone in type 2 diabetes.

Annals of Internal Medicine — Mon, 15 Aug 2011 23:00:00 +0100

Authors: PMID: 21844545 [PubMed - in process] (Source: Annals of Internal Medicine)

Danger warning for herbal slimming products

OnMedica Latest News — Thu, 11 Aug 2011 23:00:00 +0100

UK medicines watchdog issues stroke and heart attack alertRelated items from OnMedicaExperts predict rapid growth of remote diagnosis for patientsFake medicine warning hits cinemasRisk/benefit balance of alteplase shifts quicklyNew warning on epilepsy drugs in pregnancyRegulators suspend Avandia over safety concerns (Source: OnMedica Latest News)

Zebrafish obesogenic test: a tool for screening molecules that target adiposity [Methods]

The Journal of Lipid Research — Thu, 11 Aug 2011 23:00:00 +0100

We describe a short-term assay method, the zebrafish obesogenic (ZO) test, for examining the effects of diet, drugs, and environmental contaminants, singly or in combination, on white adipose tissue (WAT) dynamics in live larvae. The ZO test is an intermediate step in obesity research, between in vitro and rodent assays, and may be also used to study the effect of environmental toxicants on the adiposity of aquatic species. The procedure, using Nile Red (NR) fluorescent probe to reveal adipocyte lipid droplets, is suitable for pharmaceutical or toxicological screening. Larvae treated at an environmentally-relevant concentration of tributyltin chloride (TBT), an environmental obesogen, exhibited a remarkable increase in adiposity, irrespective of the lipid composition of the background diet...

Avandia Lawyers: PLG Law Group Opens Up Services For Those Who Wish To...

PRWeb: Medical Pharmaceuticals — Thu, 11 Aug 2011 07:17:43 +0100

PLG Law Group is a Los Angeles based firm that has helped a number of families in regards to injuries allegedly caused by the drug Avandia....(PRWeb August 08, 2011)Read the full story at http://www.prweb.com/releases/2011/8/prweb8680891.htm (Source: PRWeb: Medical Pharmaceuticals)

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Organotins Are Potent Activators of PPAR{gamma} and Adipocyte Differentiation in Bone Marrow Multipotent Mesenchymal Stromal Cells

Toxicological Sciences — Wed, 10 Aug 2011 23:00:00 +0100

Adipocyte differentiation in bone marrow is potentially deleterious to both bone integrity and lymphopoiesis. Here, we examine the hypothesis that organotins, common environmental contaminants that are dual ligands for peroxisome proliferator–activated receptor (PPAR) and its heterodimerization partner retinoid X receptor (RXR), are potent activators of bone marrow adipogenesis. A C57Bl/6-derived bone marrow multipotent mesenchymal stromal cell (MSC) line, BMS2, was treated with rosiglitazone, a PPAR agonist, bexarotene, an RXR agonist, or a series of organotins. Rosiglitazone and bexarotene potently activated adipocyte differentiation; however, bexarotene had a maximal efficacy of only 20% of that induced by rosiglitazone. Organotins (tributyltin [TBT], triphenyltin, and dibutyltin)...

Neuroprotection by rosiglitazone in transient focal cerebral ischemia might not be mediated by glutamate transporter‐1#

Journal of Neuroscience Research — Tue, 09 Aug 2011 14:19:55 +0100

AbstractGlutamate transport represents a key mechanism for maintaining low level of glutamate in the extracellular milieu to restrict the excitotoxic action of glutamate released during ischemia/reperfusion (I/R) injury. Recently, it has been reported that glutamate transporter‐1 (GLT‐1) is a novel target for peroxisome proliferator‐activated receptor‐γ (PPARγ) agonist, which shows neuroprotection following oxygen glucose deprivation (OGD) in neuronal–astrocytic cocultures. Hence, the present study was undertaken to investigate the role of rosiglitazone in neuroprotection mediated by GLT‐1 following focal cerebral I/R injury in rat. We found that rosiglitazone (2 mg/kg i.p) administered pre‐ or post‐I/R injury significantly improved behavioral outcome and decreased cerebr...

Managing Risk in Developing Transplant Immunosuppressive Agents: The New Regulatory Environment

American Journal of Transplantation — Mon, 08 Aug 2011 23:00:00 +0100

This article outlines the objectives and limitations of REMS and PMRs, with a focus on how these regulatory measures may impact the clinical specialty of transplantation. The article also briefly describes efforts to address aspects of drug safety less amenable to management through REMS and PMRs. (Source: American Journal of Transplantation)

Metabolic effects of benzylidene thiazolidinedione derivatives in high-fat fed mice

Medicinal Chemistry Research — Mon, 08 Aug 2011 19:50:05 +0100

This study suggests that these BTZDs derivatives not only reduce insulin resistance in high-fat fed mice, but also ameliorate associated hyperinsulinemia, hyperglycemia, and hyperlipidemia. Additionally, none of the derivatives exerted any major adverse effect on liver transaminases or body weight. Content Type Journal ArticlePages 1-7DOI 10.1007/s00044-011-9764-4Authors Tiago Gomes Araújo, Departamento de Bioquímica, CCB, UFPE, Universidade Federal de Pernambuco, Av. Prof. Moraes Rego, S/N, Cidade Universitária, 50670-901 Recife, PE, BrazilBruno Melo Carvalho, Departamento de Bioquímica, CCB, UFPE, Universidade Federal de Pernambuco, Av. Prof. Moraes Rego, S/N, Cidade Universitária, 50670-901 Recife, PE, BrazilCaíque Silveira Martins da Fonseca, Departamento de Bioquímica,...

Rosiglitazone risks outweigh benefits in PCOS

Modern Medicine — Thu, 04 Aug 2011 23:00:00 +0100

NEW YORK (Reuters Health) - The new anti-diabetic drug rosiglitazone is somewhat helpful in polycystic ovarian syndrome (PCOS), but at too high a price, Chinese researchers say. (Source: Modern Medicine)

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Metformin prevents anti-osteogenic in vivo and ex vivo effects of rosiglitazone in rats.

European Journal of Pharmacology — Thu, 04 Aug 2011 23:00:00 +0100

In conclusion, in rodent models metformin not only induces direct osteogenic in vivo and ex vivo actions, but when it is administered orally in combination with rosiglitazone it can prevent several of the adverse effects that this thiazolidenedione shows on bone tissue. PMID: 21839072 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)

Discordant Effects on Central Obesity, Hepatic Insulin Resistance, and Alanine Aminotransferase of Low‐dose Metformin and Thiazolidinedione Combination Therapy in Patients with Impaired Glucose Tolerance

Diabetes, Obesity and Metabolism — Tue, 02 Aug 2011 23:00:00 +0100

Alanine aminotransferase (ALT) predicts incident type 2 diabetes (T2DM), possibly reflecting early fatty liver and hepatic insulin resistance. Thiazolidinediones and metformin can improve fatty liver and hepatic insulin resistance, respectively. In the Canadian Normoglycemia Outcome Evaluation trial, rosiglitazone/metformin (Rosi/Met)(4/1000mg) reduced incident T2DM by 66% in subjects with impaired glucose tolerance. For insight on the hepatic effects of this therapy in relation to T2DM, we evaluated the temporal changes in waist, hepatic insulin sensitivity (1/HOMA‐IR), and ALT in the Rosi/Met (n=103) and placebo (n=104) arms over median 3.9‐years. Waist did not differ between the arms. Hepatic insulin sensitivity improved in the Rosi/Met arm in Year 1, but deteriorated thereafter as ...

Big Shift Seen in Prescribing Patterns for Type 2

Clinical Endocrinology News — Sun, 31 Jul 2011 23:00:00 +0100

Major Finding: The relative proportion of prescriptions for rosiglitazone, pioglitazone, and other medications was 44%, 50%, and 6% in 2005 and 2%, 18%, and 80% in 2010. (Source: Clinical Endocrinology News)

How doctors practice evidence‐based medicine

Journal of Evaluation in Clinical Practice — Sun, 31 Jul 2011 23:00:00 +0100

Conclusions Our study suggested that EBM was still not well practised, using rosiglitazone prescription as a study case. Further education and encouragement to strengthen physicians' EBM practice remain urgently needed within the medical community. (Source: Journal of Evaluation in Clinical Practice)

Rosiglitazone Investigated for Neuropathic PainRosiglitazone Investigated for Neuropathic Pain

Medscape Today Headlines — Fri, 29 Jul 2011 21:11:22 +0100

The controversial diabetes drug is now being explored as a pain medication. Medscape Medical News (Source: Medscape Today Headlines)

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Anecdotes are great – if they convey data accurately | Ben Goldacre

Guardian Unlimited Science — Fri, 29 Jul 2011 18:01:00 +0100

Channel 4 reported that a study in the Lancet showed a new drug had reduced the symptoms of Duchenne's muscular dystrophy. Unfortunately, the study shows no such thingOn Channel 4 News, scientists have found a new treatment for Duchenne's muscular dystrophy. "A study in the Lancet today shows a drug injected weekly for three months appears to have reduced the symptoms" they say. "While it's not a cure, it does appear to reduce the symptoms."Unfortunately, the study shows no such thing. The gene for making a muscle protein called dystrophin is damaged in patients with DMD. The Lancet paper shows a new treatment led to some restoration of dystrophin production in some children in a small unblinded study.That's not the same as symptoms improving. But Channel 4 reiterates its ca...

AVANDAMET (Rosiglitazone Maleate And Metformin Hydrochloride) Tablet, Film Coated [Physicians Total Care, Inc.]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Fri, 29 Jul 2011 05:00:00 +0100

Updated Date: Jul 29, 2011 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

Opposing actions of rosiglitazone and resveratrol on mineralization in human vascular smooth muscle cells

Journal of Molecular and Cellular Cardiology — Fri, 29 Jul 2011 04:00:00 +0100

In conclusion, this study reveals novel insights into the relationship of rosiglitazone and cardiovascular events by providing a model that links rosiglitazone-induced osteoblast-like differentiation, oxidative stress and apoptosis with mineralization in VSMCs. In addition, we position resveratrol in this model acting to reduce rosiglitazone-induced oxidative stress, osteoblast-like VSMC differentiation and mineralization.Highlights: ► We study the regulation of vascular mineralization using a human VSMC in vitro model. ► Rosiglitazone stimulates mineralization partly via caspase-dependent apoptosis. ► Rosiglitazone-induced oxidative stress correlates with osteoblast-like differentiation phenotype. ► Resveratrol reduces osteoblast-like differentiation. ► Resveratrol counteracts t...

Selenium Up-regulates H-PGDS [Metabolism]

Journal of Biological Chemistry — Thu, 28 Jul 2011 23:00:00 +0100

The plasticity of macrophages is evident from their dual role in inflammation and resolution of inflammation that are accompanied by changes in the transcriptome and metabolome. Along these lines, we have previously demonstrated that the micronutrient selenium increases macrophage production of arachidonic acid (AA)-derived anti-inflammatory 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and decreases the proinflammatory PGE2. Here, we hypothesized that selenium modulated the metabolism of AA by a differential regulation of various prostaglandin (PG) synthases favoring the production of PGD2 metabolites, Δ12-PGJ2 and 15d-PGJ2. A dose-dependent increase in the expression of hematopoietic-PGD2 synthase (H-PGDS) by selenium and a corresponding increase in Δ12-PGJ2 and 15d-PGJ2 in RAW264.7 mac...

Trans-10, cis-12 conjugated linoleic acid and the PPAR-γ agonist rosiglitazone attenuate lipopolysaccharide-induced TNF-α production by bovine immune cells

Domestic Animal Endocrinology — Thu, 28 Jul 2011 23:00:00 +0100

The objective of this study was to examine the effect of exogenous conjugated linoleic acid (CLA) and PPAR-γ agonist, rosiglitazone, on LPS-induced tumor necrosis factor α (TNF-α) production by cultured whole blood from prepubertal Holstein heifers (mean age, 5.5 mo). Compared with unstimulated cells, addition of LPS (10 μg/mL) to the culture medium increased (P < 0.03) peripheral blood mononuclear cell proliferation ≤2.5-fold. Coincubation with interferon γ (5 ng/mL) further stimulated (P < 0.01) the lymphoproliferative response to LPS. Lipopolysaccharide increased (P < 0.01) TNF-α concentration in cultured whole blood in a dose- and time-dependent manner. The greatest TNF-α stimulation occurred after 12 h of exposure to 1 μg/mL LPS. Coincubation with trans-10, cis-12 CLA isomer...

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11-Hydroxy-β-steroid dehydrogenase gene expression in canine adipose tissue and adipocytes: Stimulation by lipopolysaccharide and tumor necrosis factor α

Domestic Animal Endocrinology — Thu, 28 Jul 2011 23:00:00 +0100

Abstract: The enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD-1) is expressed in a number of tissues in rodents and humans and is responsible for the reactivation of inert cortisone into cortisol. Its gene expression and activity are increased in white adipose tissue (WAT) from obese humans and may contribute to the adverse metabolic consequences of obesity and the metabolic syndrome. The extent to which 11β-HSD-1 contributes to adipose tissue function in dogs is unknown; the aim of the present study was to examine 11β-HSD-1 gene expression and its regulation by proinflammatory and anti-inflammatory agents in canine adipocytes. Real-time PCR was used to examine the expression of 11β-HSD-1 in canine adipose tissue and canine adipocytes differentiated in culture. The mRNA encoding 11...

Selective Glucocorticoid Receptor (GR-II) Antagonist Reduces Body Weight Gain in Mice

Interdisciplinary Perspectives on Infectious Diseases — Thu, 28 Jul 2011 13:57:28 +0100

Previous research has shown that mifepristone can prevent and reverse weight gain in animals and human subjects taking antipsychotic medications. This proof-of-concept study tested whether a more potent and selective glucocorticoid receptor antagonist could block dietary-induced weight gain and increase insulin sensitivity in mice. Ten-week-old, male, C57BL/6J mice were fed a diet containing 60% fat calories and water supplemented with 11% sucrose for 4 weeks. Groups (n=8) received one of the following: CORT 108297 (80 mg/kg QD), CORT 108297 (40 mg/kg BID), mifepristone (30 mg/kg BID), rosiglitazone (10 mg/kg QD), or vehicle. Compared to mice receiving a high-fat, high-sugar diet plus vehicle, mice receiving a high-fat, high-sugar diet plus either mifepristone o...

Use pioglitazone only in selected patients, says EMA guidance

OnMedica Latest News — Wed, 27 Jul 2011 23:00:00 +0100

Avoid drug in haematuria or bladder cancer, and monitor regularlyRelated items from OnMedicaRegulators suspend Avandia over safety concernsThyroid patients need better monitoringBreast cancer rate falls with decline in HRT useHigher breast cancer risk with HRTProstate cancer therapy raises colorectal cancer risk (Source: OnMedica Latest News)

Avandia May Help Prevent Neuropathic Pain

Health News from Medical News Today — Tue, 26 Jul 2011 07:00:00 +0100

The diabetes drug rosiglitazone (Avandia) can control inflammation leading to nerve damage and abnormal pain responses, suggests a paper in the August issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS). Rosiglitazone works by blocking a specific pathway called PPAR-gamma which appears to play a critical role in the development of disabling neuropathic pain... (Source: Health News from Medical News Today)

Reactivity of aorta and mesenteric resistance arteries from the obese spontaneously hypertensive rat. Effects of glitazones.

American Journal of Physiology. Heart and Circulatory Physiology — Thu, 21 Jul 2011 23:00:00 +0100

Authors: Mendizabal Y, Llorens S, Nava E The obese spontaneously hypertensive rat (SHROB) is a model of metabolic syndrome in which, to our knowledge, vascular function has never been studied. The actions of the insulin sensitizers, glitazones, on vascular function have not been analyzed either. Our purpose is to characterize micro- and macrovascular responses of SHROB and to study the effects of glitazones on these responses. Reactivity of mesenteric resistance arteries (MRA) and aorta from SHROB and control rats to cumulative concentrations of phenylephrine, acetylcholine and (SNP) was myographically analyzed. Some animals were orally treated with rosiglitazone (3 mg kg(-1) day(-1), 3 weeks) and myography performed. Phenylephrine, acetylcholine and sodium nitroprusside (SNP) dose-res...

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Can the Electrophysiological Action of Rosiglitazone Explain its Cardiac Side Effects?

Current Medicinal Chemistry — Wed, 20 Jul 2011 23:00:00 +0100

Authors: Szebeni A, Szentandrássy N, Pacher P, Simkó J, Nánási PP, Kecskeméti V Recent large clinical trials found an association between the antidiabetic drug rosiglitazone therapy and increased risk of cardiovascular adverse events. The aim of this report is to elucidate the cardiac electrophysiological properties of rosiglitazone (R) on isolated rat and murine ventricular papillary muscle cells and canine ventricular myocytes using conventional microelectrode, whole cell voltage clamp, and action potential (AP) voltage clamp techniques. In histidine-decarboxylase knockout mice as well as in their wild types R (1-30 µM) shortened AP duration at 90% level of repolarization (APD90) and increased the AP amplitude (APA) in a concentration-dependent manner. In rat ventricular papill...

Bone marrow fat has brown adipose tissue characteristics, which are attenuated with aging and diabetes

Bone — Mon, 18 Jul 2011 04:00:00 +0100

In conclusion, the metabolic phenotype of marrow fat combines both BAT and WAT characteristics. Decrease in BAT-like characteristics with aging and diabetes may contribute to the negative changes in the marrow environment supporting bone remodeling and hematopoiesis.This article is part of a Special Issue entitled: Interactions Between Bone, Adipose Tissue and Metabolism.Highlights: ► In this study we examined phenotype of marrow fat by analysis of gene expression. ► The analysis included the expression of white fat and brown fat gene markers. ► Our studies show that marrow fat possesses brown adipocyte tissue characteristics. ► Brown phenotype of marrow fat is attenuated with aging and diabetes. (Source: Bone)

PPARγ Ligands Regulate NADPH Oxidase, eNOS, and Barrier Function in the Lung Following Chronic Alcohol Ingestion

Alcoholism: Clinical and Experimental Research — Sun, 17 Jul 2011 23:00:00 +0100

Conclusions: These results indicate that PPARγ activation reduced expression of eNOS, Nox1, Nox4, the production of reactive species, and barrier dysfunction caused by chronic alcohol ingestion and suggest that PPARγ represents a novel therapeutic target for strategies designed to reduce the risk of lung injury in patients with a history of chronic alcohol ingestion. (Source: Alcoholism: Clinical and Experimental Research)

PPARγ Ligands Regulate NADPH Oxidase, eNOS, and Barrier Function in the Lung Following Chronic Alcohol Ingestion.

Alcoholism, Clinical and Experimental Research — Sun, 17 Jul 2011 23:00:00 +0100

Conclusions: These results indicate that PPARγ activation reduced expression of eNOS, Nox1, Nox4, the production of reactive species, and barrier dysfunction caused by chronic alcohol ingestion and suggest that PPARγ represents a novel therapeutic target for strategies designed to reduce the risk of lung injury in patients with a history of chronic alcohol ingestion. PMID: 21762184 [PubMed - as supplied by publisher] (Source: Alcoholism, Clinical and Experimental Research)