Alzheimer's disease (AD) is characterized by the extracellular deposition of beta-amyloid fibrils within the brain and the subsequent association and phenotypic activation of microglial cells associated with the amyloid plaque. The activated microglia mount a complex local proinflammatory response with the secretion of a diverse range of inflammatory products. Nonsteroidal anti-inflammatory drugs (NSAIDs) are efficacious in reducing the incidence and risk of AD and significantly delaying disease progression. A recently appreciated target of NSAIDs is the ligand-activated nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma). PPARgamma is a DNA-binding transcription factor whose transcriptional regulatory actions are activated after agonist binding. We report that NSAIDs, drugs of the thiazolidinedione class, and the natural ligand prostaglandin J2 act as agonists for PPARgamma and inhibit the beta-amyloid-stimulated secretion of proinflammatory products by microglia and monocytes responsible for neurotoxicity and astrocyte activation. The activation of PPARgamma also arrested the differentiation of monocytes into activated macrophages. PPARgamma agonists were shown to inhibit the beta-amyloid-stimulated expression of the cytokine genes interleukin-6 and tumor necrosis factor alpha. Furthermore, PPARgamma agonists inhibited the expression of cyclooxygenase-2. These data provide direct evidence that PPARgamma plays a critical role in regulating the inflammatory responses of microglia and monocytes to beta-amyloid. We argue that the efficacy of NSAIDs in the treatment of AD may be a consequence of their actions on PPARgamma rather than on their canonical targets the cyclooxygenases. Importantly, the efficacy of these agents in inhibiting a broad range of inflammatory responses suggests PPARgamma agonists may provide a novel therapeutic approach to AD.
The majority of patients with WG are referred to otolaryngology because of involvement of the sinonasal tract. Noncosmetic functional sinonasal procedures are indicated in a minority of patients. Sinonasal morbidity remains significant even after surgery. It is greatest for orbital pseudotumor, but also common for CRS and nasolacrimal duct obstruction.
This new staging system for IP provides information about prognosis (as operationally defined by RR) for IP managed by advanced endoscopic techniques. In contrast, other staging systems for IP reflect surgeon's judgment rather than outcomes data. This new classification for IP provides important objective data for preoperative planning and patient counseling.
This study evaluated clinical factors and postoperative complications to determine which ones were associated with 30-day unplanned hospital readmission among patients undergoing surgery for malignant tumors of the head and neck. Further understanding of which complications are associated with unplanned readmission after head and neck surgery will allow for improved risk stratification and development of postoperative care protocols to reduce unplanned hospital readmission.
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