Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis.

Background: Neurosurgical resection is the standard treatment for subependymal giant-cell astrocytomas in patients with the tuberous sclerosis complex. An alternative may be the use of everolimus, which inhibits the mammalian target of rapamycin, a protein regulated by gene products involved in the tuberous sclerosis complex.

Methods: Patients 3 years of age or older with serial growth of subependymal giant-cell astrocytomas were eligible for this open-label study.

Ciglitazone, a novel inhibitor of lung apoptosis following hemorrhagic shock.

Apoptosis or programmed cell death has been demonstrated to play a role in the development of lung injury following hemorrhagic shock. A major pathway modulating the apoptotic response is the phosphatidylinositol 3-kinase/serine/threonine kinase (PI3K/Akt) pathway. Ciglitazone, a peroxisome proliferator-activated receptor-y (PPARy) ligand has previously been shown to attenuate lung inflammation following hemorrhagic shock.

Ciglitazone ameliorates lung inflammation by modulating the inhibitor kappaB protein kinase/nuclear factor-kappaB pathway after hemorrhagic shock.

Objective: Peroxisome proliferator-activated receptor-gamma is a ligand-activated transcription factor. Ciglitazone, a peroxisome proliferator-activated receptor-gamma ligand, has been shown to provide beneficial effects in experimental models of sepsis and ischemia/reperfusion injury. We investigated the effects of ciglitazone on lung inflammation after severe hemorrhage.

Peroxisome proliferator activated receptor gamma is not necessary for the development of LPS-induced tolerance in macrophages.

Peroxisome proliferator activated receptor-gamma (PPARgamma) has been reported to exert anti-inflammatory properties in endotoxic shock and sepsis. One phenomenon that alters the inflammatory response to endotoxin [lipopolysaccharide (LPS)] is endotoxin tolerance, which is caused by previous exposure to endotoxin. Here, we investigate whether changes in endogenous PPARgamma function regulate this phenomenon using three different models of LPS-induced tolerance in macrophages.

Therapeutic effect of epigallocatechin-3-gallate in a mouse model of colitis.

Epigallocatechin-3-gallate (EGCG), a green tea catechin, has been shown to inhibit signaling pathways involved in inflammation, including nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1), which are important inducers of pro-inflammatory mediators. Aim of our study was to evaluate the therapeutic efficacy of EGCG in experimental colitis, which was induced by rectal administration of trinitrobenzenesulfonic acid (TNBS) in C57/BL6 mice. Mice were treated twice daily with vehicle or with EGCG (10 mg/kg) intraperitoneally, and sacrificed on days 1, 3, and 7 after TNBS administration.

Diverse cardioprotective signaling mechanisms of peroxisome proliferator-activated receptor-gamma ligands, 15-deoxy-Delta12,14-prostaglandin J2 and ciglitazone, in reperfusion injury: role of nuclear factor-kappaB, heat shock factor 1, and Akt.

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a nuclear receptor that regulates diverse biological functions including inflammation. The PPARgamma ligands have been reported to exert cardioprotective effects and attenuate myocardial reperfusion injury. Here, we examined the molecular mechanisms of their anti-inflammatory effects.

Proinsulin c-peptide exerts beneficial effects in endotoxic shock in mice.

Objective: Insulin connecting peptide (c-peptide) aids the folding of proinsulin and has been considered to have little biological activity. Recently, c-peptide has been shown to improve diabetic neuropathy and nephropathy as well as vascular inflammation. In vitro studies have reported that c-peptide may activate peroxisome proliferator-activated receptor-gamma, a nuclear transcription factor that plays a regulatory role in inflammation.