Rosen CJ.The rosiglitazone story-lessons from an FDA Advisory Committee meeting. N Engl J Med 357:844-846

Maine Center for Osteoporosis, St. Joseph Hospital, Bangor, USA.
New England Journal of Medicine (Impact Factor: 55.87). 09/2007; 357(9):844-6. DOI: 10.1056/NEJMp078167
Source: PubMed
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    • "Consistently, mutations of the PPARγ gene have been implicated in lipodystrophy as well as other metabolic diseases such as hypertension and insulin resistance in humans [11-13]. Antidiabetic insulin-sensitizing drug thiazolidinediones (TZDs) such as Rosiglitasone have been identified as potent and selective ligands of PPARγ [14] but these drugs have undesirable side effects [15]. "
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    ABSTRACT: The nuclear receptor PPARγ is a master regulator of adipogenesis. PPARγ is highly expressed in adipose tissues and its expression is markedly induced during adipogenesis. In this review, we describe the current knowledge, as well as future directions, on transcriptional and epigenetic regulation of PPARγ expression during adipogenesis. Investigating the molecular mechanisms that control PPARγ expression during adipogenesis is critical for understanding the development of white and brown adipose tissues, as well as pathological conditions such as obesity and diabetes. The robust induction of PPARγ expression during adipogenesis also serves as an excellent model system for studying transcriptional and epigenetic regulation of cell-type-specific gene expression.
    Cell and Bioscience 05/2014; 4(1):29. DOI:10.1186/2045-3701-4-29 · 3.63 Impact Factor
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    • "Antidiabetic drugs like thiazides also cause bone loss.40 Many studies in humans as well as in animals have shown that bone loss is accelerated by thiazoles.41–43 Rosiglitazone decreases bone quality by increasing porosity.40 "
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    ABSTRACT: Men undergo gradual bone loss with aging, resulting in fragile bones. It is estimated that one in five men will suffer an osteoporotic fracture during their lifetime. The prognosis for men after a hip fracture is very grim. A major cause is reduction of free testosterone. Many other factors result in secondary osteoporosis, including treatment for other diseases such as cancer and diabetes. Patients should be screened not only for bone density but also assessed for their nutritional status, physical activity, and drug intake. Therapy should be chosen based on the type of osteoporosis. Available therapies include testosterone replacement, bisphosphonates, and nutritional supplementation with calcium, vitamin D, fatty acids, and isoflavones, as well as certain specific antibodies, like denosumab and odanacatib, and inhibitors of certain proteins.
    Drug Design, Development and Therapy 08/2013; 7:849-860. DOI:10.2147/DDDT.S46101 · 3.03 Impact Factor
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    • "Synthetic thiazolidinedione PPARγ ligands, including rosiglitazone and pioglitazone, enhance insulin sensitivity and have been employed in the treatment of type 2 diabetes(Yki-Jarvinen, 2004). Although the long-term use of rosiglitazone in diabetic patients has been associated with adverse outcomes (Home et al., 2007, Nissen and Wolski, 2007, Rosen, 2007), it is not clear if similar adverse effects would be observed in short-term applications of this drug in nondiabetic subjects. Further, pioglitazone was not associated with adverse cardiovascular outcomes in diabetic subjects (Dormandy et al., 2005, Erdmann et al., 2007, Lincoff et al., 2007, Wilcox et al., 2007). "
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    ABSTRACT: Chronic alcohol ingestion increases the incidence and severity of the acute respiratory distress syndrome (ARDS), where reactive species contribute to alveolar-capillary barrier dysfunction and noncardiogenic pulmonary edema. Previous studies demonstrated that chronic alcohol ingestion increased lung NADPH oxidase and endothelial nitric oxide synthase (eNOS) expression and that ligands for the peroxisome proliferator-activated receptor gamma (PPARγ) reduced NADPH oxidase expression. Therefore, we hypothesized that the PPARγ ligand, rosiglitazone, would attenuate alcohol-induced NADPH oxidase expression and pulmonary barrier dysfunction. C57Bl/6 mice were treated ± alcohol in drinking water (20% w/v) for 12 weeks. During the final week of alcohol treatment, mice were gavaged with rosiglitazone (10 mg/kg/d) or vehicle. Selected animals were treated twice with lipopolysaccharide (LPS, 2 mg/kg IP) prior to sacrifice. Pulmonary barrier dysfunction was estimated from protein content of bronchoalveolar lavage (BAL) fluid. LPS treatment increased BAL protein in alcohol-fed but not control mice, and rosiglitazone attenuated LPS and alcohol-induced pulmonary barrier dysfunction. Alcohol- and LPS-induced increases in lung eNOS, Nox1, and Nox4 expression were attenuated by rosiglitazone. In vitro, alcohol (0.10% w/v) increased H(2)O(2) production, barrier dysfunction, eNOS, Nox1, and Nox4 expression in human umbilical vein endothelial cell (HUVEC) monolayers, effects also attenuated by rosiglitazone (10 μM). Alcohol-induced HUVEC barrier dysfunction was attenuated by inhibition of NOS or addition of the eNOS cofactor, tetrahydrobiopterin. 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.
    Alcoholism Clinical and Experimental Research 07/2011; 36(2):197-206. DOI:10.1111/j.1530-0277.2011.01599.x · 3.21 Impact Factor
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