Objectives: To show the evidence that constituents of the innate immunity contribute to the etiology of late-onset AD. Methods: Evaluation of the relationship between the constituents of the innate immunity and genetic risk factors for late-onset AD. Results: Complement activation and activated microglia are early neuropathogical events in AD brains. Genome-wide association studies have demonstrated gene loci that are linked to the complement system. The production capacity for inflammatory cytokines is under genetic control and the
offspring with a parental history of late-onset AD have a higher production capacity for inflammatory cytokines. Conclusion: Epidemiological and genetic data suggest that the innate immunity is involved in the etiology of late-onset AD. Copyright (C) 2012 S. Karger AG, Basel”
“Several JQ-EZ-05 studies have shown ASP2215 mouse that Purkinje cells die by apoptosis in organotypic slice cultures from postnatal 3-day-old (P3) mice. This cell death is age-dependent and has been proposed as indirect evidence for the programmed Purkinje cell death occurring in in vivo cerebellum. Here, we studied whether c-jun N-terminal kinase (JNK) and p38 kinase pathways contribute to the Purkinje cell
death observed in cerebellar slice cultures obtained from P3 mice. Slice culture treatment with D-JNKI1 or SB203580, respectively inhibitors of JNK and p38 MAP kinases, results in a better survival of Purkinje cells. Interestingly, the combined treatment with the two inhibitors potentiated single treatment effects. These results suggest that p38 and JNK pathways might be differently implicated in this Purkinje cell death. Time course experiments found p38 activation immediately
post-slicing, whereas JNK activation was detected only 2 h after the culture. We hypothesize BMS-754807 manufacturer that p38 activation might be due to the “”sliced condition,”" and JNK activation might be more specific to P3 age-dependent cell death. The study of JNK and p38 activation in cerebellar lysates from P0 slice culture confirmed JNK activation being specific for the P3 explants, whereas p38 is activated both from P0 and P3 cerebellar slice culture lysates. These results suggest that p38 is activated by the slicing, whereas JNK activation is related to developmental Purkinje cell death.”
“Advanced biotechnological techniques and new polymers have led to the development of many innovative intravitreal drug delivery systems. Some designs are still in an experimental phase while others have gained widespread acceptance and are commercially available. Since steroids are a mainstay of therapy for uveitis and macular edema, new intravitreal implants have been developed to provide continuous release of corticosteroids over prolonged spans of time with reduced systemic adverse effects.