PPARs are transcription factors that reside in the nucleus and become activated by ligands such as thiazolidinediones. Thiazolidinediones enter the cell, bind to the nuclear receptors, and alter the expression of genes. The several PPARs include PPARα, PPARβ/δ, and PPARγ. Thiazolidinediones bind to PPARγ. PPARs are expressed in fat cells, cells of the liver, muscle, heart, and inner wall (endothelium) and smooth muscle of blood vessels. PPARγ is expressed mainly in fat tissue, where it regulates genes involved in fat cell (adipocyte) differentiation, fatty acid uptake and storage, and glucose uptake. It is also found in pancreatic beta cells, vascular endothelium, and macrophages Rosiglitazone is a selective ligand of PPARγ and has no PPARα-binding action. Other drugs bind to PPARα. Rosiglitazone also appears to have an anti-inflammatory effect in addition to its effect on insulin resistance. Nuclear factor kappa-B (NF-κB), a signaling molecule, stimulates the inflammatory pathways. NF-κB inhibitor (IκB) downregulates the inflammatory pathways. When patients take rosiglitazone, NF-κB levels fall and IκB levels increase. History
Rosiglitazone was approved by the US FDA in 1999 and by the EMA in 2000;  the EMA however required two postmarketing studies on longterm adverse effects, one for chronic heart failure and the other for cardiovascular effects. Society and culture
Sales
US sales of the drug were of $2.2 billion in 2006. Sales in 2Q 2007 down 22% compared to 2006. 4Q 2007 sales down to $252 million.Though sales have gone down since 2007 due to safety concerns, Avandia sales for 2009 totalled $1.2 billion worldwide.
Regarding chronic subdural hematoma (CSDH) surgery, a postoperative volume of pneumocephalus greater than 15mL puts a patient at increased risk of CSDH recurrence; in fact, for every milliliter of air entering the cranial cavity after CSDH evacuation, the recurrence risk increases by 4%. Efforts are made by neurosurgeons to reduce pneumocephalus volume during surgery, and thus, subsequent brain shift. Additional images
Footnotes


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