Cytokine-induced cell death in immortalized Schwann cells: roles of nitric oxide and cyclic AMP

Tumor necrosis factor-alpha and interferon-gamma are pleiotropic cytokines that regulate Schwann cell responses during injury and inflammatory demyelination. We have previously shown that cyclic AMP (cAMP)-elevating agents decrease the demyelination and Wallerian degeneration in experimental allergic neuritis. In this study, we examined the role of cAMP in cytokine-mediated signaling in a spontaneously immortal Schwann cell clone (iSC). We found that tumor necrosis factor-alpha and interferon-gamma exert synergistic inhibitory action on Schwann cell viability via the production of nitric oxide (NO) and ceramide (cer). Furthermore, we found that: (i) NO synthase inhibitors attenuate the cytokine-induced cer accumulation and cell death indicating that NO acts upstream of cer; and (ii) cytokine-induced cell death is decreased in iSCs pretreated continuously for 48-72 h with forskolin, an activator of adenylate cyclase. Although forskolin modulates the phosphorylation of ERKs and Akt, it decreases the susceptibility of iSC to cytokines via a separate mechanism operating after NO induction and before cer accumulation. We propose that the protective effect of cAMP-elevating agents in experimental allergic neuritis may be mediated in part via modulation of Schwann cell responses to cytokines.     

Congenital Postero-Lateral Diaphragmatic Hernia in Children

Congenital diaphragmatic hernia must be seriously considered in the differential diagnosis of acute respiratory distress in neonates as well as in older infants who present with chronic progressive gastrointestinal and respiratory symptoms. An x-ray film of the chest is mandatory and is almost always diagnostic. Immediate nasogastric decompression of the stomach, with simultaneous fluid and electrolyte replacement and prompt surgical intervention offers the patient the best chance of survival.