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Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that belongs to the secretin/glucagon/vasoactive intestinal polypeptide superfamily. The PACAPergic system is actively expressed in the developing cerebellum of mammals. In particular, PACAP receptors are expressed by granule cell precursors suggesting a role of the peptide in neurogenesis of this cell type. Consistent with this hypothesis, several studies reported antiapoptotic effects of PACAP in the developing cerebellum. On the other hand, the sphingomyelin metabolites ceramides are recognized as important signaling molecules that play pivotal roles during neuronal development. Ceramides, which production can be induced by death factors such as FasL or TNFalpha, are involved in the control of cell survival during brain development through activation of caspase-dependent mechanisms. The present review focuses on the interactions between PACAP and ceramides in the control of granule cell survival and on the transduction mechanisms associated with the anti- and proapoptotic effects of PACAP and ceramides, respectively. [ABSTRACT FROM AUTHOR]

Transplantation of neuronal precursor cells (NPCs) into the central nervous system could represent a powerful therapeutical tool against neurodegenerative diseases. Unfortunately, numerous NPCs die shortly after transplantation, predominantly due to caspase-dependent apoptosis. Using a culture of cerebellar neuronal precursors, we have previously demonstrated protective effect of the neuropeptide PACAP, which suppresses ceramide-induced apoptosis by blockade of the mitochondrial apoptotic pathway. The main objective of this study was to determine whether Bax repression can promote survival of NPCs allotransplanted into a host animal. In vivo and ex vivo experiments revealed that C2-ceramide increases Bax expression, while PACAP reverses this effect. In vitro tests using cerebellar NPCs demonstrated that the Bax-specific small interfering RNA (siRNA) could reduce their death and caspase-3 cleavage within the first 24 h. BrdU-labelled NPCs were subjected to transfection procedure with or without siRNA introduction before using for in vivo transplantation. Twenty-four hours after, the allografted NPCs containing siRNA showed significantly reduced level of caspase-3 cleavage, and the volume of their implants was almost twofold higher than in the case of empty-transfected precursors. These data evidence an important role of Bax in life/death decision of grafted NPCs and suggest that RNA interference strategy may be applicable for maintaining NPCs survival within the critical first hours after their transplantation.Cell Death and Differentiation (2008) 15, 1042–1053; doi:10.1038/cdd.2008.29; published online 7 March 2008 [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to compare the operative outcome in children undergoing open vs thoracoscopic resection of bronchogenic cysts.Methods: The medical records of children who underwent the resection of bronchogenic cysts from 1990 through 2000 were reviewed. Four cyst resections were performed by the open technique and five using a thoracoscopic procedure. The age of the patients, length of hospital stay, duration of drainage, operating time, and outcome were investigated.Results: The mean age of patients undergoing the open procedure was 3 years and 3 months; the mean age for thoracoscopy patients was 7 years and 10 months (p < 0.05). The operating time for the open procedure was 70 +/- 25 min; for the laparoscopic procedure, it was 78 +/- 6 min (p, NS), except in one case with a main bronchial tail that required conversion (320 min). Duration of surgical drainage was 6.5 +/- 3 days for the open procedure and 2.5 +/- 1 days for the thoracoscopic one (p < 0.05). Hospital stay for open patients was 12 days +/- 0 days; it was 6 +/- 1.6 days for thoracoscopic patients (p < 0.01). There were no deaths. The thoracoscopic procedure failed once due to a main bronchial tail and had to be converted to an open procedure. Other early complications included a bronchopulmonary infection after an open cyst excision and an atelectasis after a thoracoscopic cyst excision. Late complications included one reoperation for incomplete excision in each of the two groups.Conclusion: Bronchogenic cyst resection can be performed safely. For complete treatment of these patients, total excision of the wall cyst is needed. In selected patients, the thoracoscopic procedure may decrease the duration of surgical drainage and length of hospital stay without increasing the operating time or MSK for complications. [ABSTRACT FROM AUTHOR]