Like native LXs, o-[9,12]-benzo-omega 6-epi-LXA(4), o-[9,12]-benzo-deoxy-LXA(4), m-[9,12]-benzo-omega 6-epi-LXA(4) and [9,14]-benzo-omega 6-(R/S)-LXA(4) demonstrated potent time-dependent reduction, at nanogram dosages, of PMN infiltration and pro-inflammatory cytokine generation in vivo in murine peritonitis and were organ protective in hind limb ischemia-reperfusion injury of the lung. The o-[9,12]-benzo-omega 6-epi-LXA(4) and m-[9,12]-benzo-omega 6-epi-LXA(4) were most potent in nanogram doses; both decreased PMN infiltration by similar to 32%, while o-[9,12]-benzo-deoxy-LXA(4) and [9,15]-omega 6-(R/S)-LXA(4) were less potent. The [9,12]-benzo-omega 6-epi-LXA(4) also activated a lipoxin A(4)
check details GPCR and increased macrophage phagocytic
activity. Taken together, these findings demonstrate a new generation of LXA(4) stable analogs that are easy to synthesize and anti-inflammatory. These benzo-LXA(4) analogs are promising tools for new therapeutic approaches as well as assessing endogenous mechanisms in anti-inflammation and resolution. (C) 2009 Elsevier Ltd. All rights reserved.”
“Cytisine (CYT), one of the principal bioactive components derived from the seeds of Cytisus laborinum L, has been widely used for central nervous system (CNS) diseases treatment. The present study investigated the protective effect of CYT on cultured cortical neural injury induced by N-methyl-D-aspartate (NMDA). Our data showed that CYT conferred protective effect against loss of cellular viability induced by brief exposure to 200 mu M NMDA in a concentration-dependent manner. CYT significantly inhibited the neuronal apoptosis see more induced by NMDA exposure by reversing intracellular Ca2+ overload and balancing Bcl-2 and Bax expression levels. Furthermore, CYT significantly reversed the up-regulation of GluN2B-containing NMDA receptors by exposure to NMDA, but it did not affect the level of GluN2A-containing NMDA receptors. These findings suggest that CYT protects cortical neurons, at least partially, by inhibiting the level of GluN2B-containing NMDA receptors and regulating Bcl-2 family. (C) 2012 Elsevier Inc. All rights reserved.”
“To
identify informal primary caregiver characteristics associated with care transitions of community-dwelling older persons with impairments VX-809 concentration in daily living activities.
Data for this study were pooled to observe transitions from Wave 1-Wave 2 and Wave 2-Wave 3 of the Second Longitudinal Survey on Aging (LSOA II). The sample includes respondents with at least one impairment in daily living activities and with an informal caregiver at baseline of each transition period (n = 2,990). Primary caregiver transitions to another informal caregiver, to formal care, to a nursing home, or to no care were modeled using multinomial logistic regression.
More than half (54%) of the surviving respondents experienced a care transition for a period of 2 years.