Moreover, the acute anticonvulsant effect of P was undiminished in fully-kindled PRKO mice. These studies suggest that P exerts disease-modifying effects in the hippocampus kindling model at doses that do not significantly affect seizure expression and motor performance, and the kindling-retarding effects

of P may occur partly through a complex PR-dependent and PR-independent mechanism. (C) 2010 Elsevier Selleck Bafilomycin A1 Ltd. All rights reserved.”
“Recent decades have witnessed the revelation of expanding roles of the vitamin D endocrine system beyond calcium and phosphorus metabolism. Along with these non-calcemic or non-classic actions of vitamin D are newly discovered therapeutic actions of vitamin D analogs in a number of pathological conditions, including kidney disease.

The kidney is the major organ involved in the synthesis of the hormonal metabolite of vitamin D, and vitamin D deficiency is a common feature of chronic kidney disease even in its early stages. Experimental data suggest that vitamin D deficiency may in turn accelerate the progression of kidney disease. Low-calcemic vitamin D analogs have exhibited selleckchem impressive therapeutic effects in various kidney disease models, with targets ranging from the NF-kappa B pathway to the renin-angiotensin system. These recent studies demonstrate that vitamin D analogs have potent renoprotective effects. The emerging experimental and clinical evidence has provided a solid foundation for the continuing exploration of vitamin D analogs in prevention and intervention in kidney disease. Kidney International (2010) 78, 134-139;doi:10.1038/ki.2009.175; published online 27 May 2009″
“The intracellular calcium overload resulting from glutamate excitotoxicity is considered major determinant for neuronal loss during cerebral ischemia. Moreover, acidosis mediated ASIC1a activation has also shown to promote intracellular calcium overload following ischemic insult. Interestingly, ASIC1a was found to be

inhibited by NSAIDs particularly flurbiprofen and ibuprofen, which could be exploited in hypoxic conditions like cerebral ischemia. This prompted us to investigate neuroprotective LGX818 effect of flurbiprofen, besides its possible downstream signaling mechanism in rodent model of focal cerebral ischemia.

The flurbiprofen treatment, 30 min prior to ischemia and 4 h post-reperfusion, afforded significant neuroprotection from ischemic injury as evidenced by reduction in cerebral infarct volume and neurobehavioral deficit. Further, an early calcium dependant rise in levels of nitrite and MDA was also found to be significantly (P < 0.01) reduced in ischemic brain regions following flurbiprofen pretreatment. It also reduced the proteolytic products (SBDPs) caused by ischemic activation of calcium dependant protease calpain.