Indeed, mTOR inhibitors appear to possess antiepileptogenic properties in animal models of acquired epilepsy
as well. Thus, mTOR dysregulation may represent a final common pathway in epilepsies of various causes. Therefore, mTOR inhibition is an exciting potential antiepileptogenic strategy with broad applications for epilepsy and could be involved in a number of treatment modalities, including the ketogenic diet. Further research is necessary to determine the clinical utility of rapamycin and other mTOR inhibitors for antiepileptogenesis, Raf inhibitor and to devise new therapeutic targets by further elucidating the signaling molecules involved in epileptogenesis. (C) 2011 Elsevier Ireland Ltd. All rights reserved.”
“Background: Although the recommended target blood pressure for patients with chronic kidney disease is < 130/80 mm Hg, this is difficult to achieve by treatment with an angiotensin BGJ398 receptor blocker alone. Addition of either a calcium channel blocker or a diuretic is suggested as second-line medication; however, which combination is most beneficial for target-organ
protection remains unknown. Methods: SHR/NDmcr-cp rats were administered no medications ( control) or low-dose olmesartan for 2 weeks and then either olmesartan at an increased dose, azelnidipine, or the hydrochlorothiazide for 3 weeks. We
assessed oxidative stress in the kidney and aorta, and endothelial function. Results: Urinary protein excretion was lower in all treated rats than in control BMS345541 cell line rats. Oxidative stress caused by activation of NAD(P)H oxidase was observed in the glomeruli and aorta of control rats and was significantly suppressed in the olmesartan/azelnidipine (Olm/Azl) groups. Combination therapy with olmesartan and hydrochlorothiazide (Olm/HCTZ) however failed to suppress oxidative stress. The Olm/Azl groups maintained the endothelial surface layer in the glomeruli and protected endothelial function in the aorta. Conclusion: In an animal model of metabolic syndrome, a combination of Olm/Azl is superior to a combination of Olm/HCTZ in terms of prevention of glomerular and vascular injuries. Copyright (C) 2011 S. Karger AG, Basel”
“Relatively little is known about the time course of the development of spontaneous recurrent seizures (i.e., epileptogenesis) after brain injury in human patients, or even in animal models. This time course is determined, at least in part, by the underlying molecular and cellular mechanisms responsible for acquired epilepsy. An understanding of the critical mechanistic features of acquired epilepsy will be useful, if not essential, for developing strategies to block or suppress epileptogenesis.