We tested if ex vivo delivery of carbon monoxide (CO) to the kidney would ameliorate the renal injury of cold storage that can complicate renal transplantation. Orthotopic syngeneic kidney transplantation was performed in Lewis rats following 24 h
of cold preservation in University of Wisconsin Selleck OTX015 solution equilibrated without or with CO (soluble CO levels about 40 mu M). Ischemia/reperfusion injury in control grafts resulted in an early upregulation of inflammatory mediator mRNAs and progressive deterioration of graft function. In contrast, the grafts preserved with CO had significantly less oxidative injury and this was associated with improved recipient survival compared to the control group. Renal injury in the control group showed considerable degradation of cytochrome P450 heme proteins, active heme metabolism and increased detrimental intracellular free heme levels. Kidney grafts preserved in CO-equilibrated solution maintained their cytochrome P450 protein levels, had normal intracellular heme levels and had less lipid peroxidation. Our results show that CO-mediated suppression of click here injurious heme-derived redox reactions offers protection of kidney grafts from cold ischemia/reperfusion injury.”
“Using drugs acting on nicotinic acetylcholine receptors (nAChRs), we examined temporal-parietal and frontal cortex, hippocampus, and cerebellum to identify sites of cognition enhancement in 4- and 27-month rabbits.
First, we compared radioligand receptor binding for neuronal alpha beta heteromeric nAChRs ([(3)H] epibatidine) and alpha(7) homomeric nAChRs ([(3)H] methyllycaconitine) in rabbits and rats. In cerebellum, nAChR levels of both species are low, about at the detection limit of the radioligand binding assays. Next, we compared nAChRs in 4- and Cell press 27-month vehicle-treated rabbits trained in delay eyeblink conditioning. Older rabbits conditioned more poorly and had lower alpha beta heteromeric nAChR binding in hippocampus than young rabbits. For cognition enhancement, galantamine ( mild cholinesterase inhibitor and allosteric modulator of nAChRs) or MEM-3389 (alpha 7nAChR agonist formerly identified as AR-R 17779) was injected before
conditioning. Drugs improved learning in both age groups. In 27-month rabbits, drugs increased expression of frontal and temporal-parietal alpha beta heteromeric nAChRs and hippocampal alpha beta and alpha 7nAChRs. In 4-month rabbits, drugs increased expression of alpha 7 homomeric nAChRs in frontal and temporal-parietal cortex and hippocampus, but increased expression of alpha beta heteromeric nAChRs only occurred in temporal- parietal cortex. Increased expression of alpha beta nAChRs was more extensive in older drug-treated rabbits, whereas increased expression of alpha 7nAChRs was more prevalent in younger drug-treated rabbits, suggesting different substrates for amelioration (27-month rabbits) vs facilitation (4-month rabbits) of learning.