OBJECTIVE: A systematic review of the literature
on the effects of dexamethasone on the brain from in vivo Selleckchem U0126 studies in humans.
METHODS: A MEDLINE database search (via the PubMed interface) and an EMBASE database search (via the Dialog interface) of the past 35 years was performed. Every article relating to human use reported in English was included. In addition, references of all eligible articles were searched to identify other possible sources.
RESULTS: Twenty-four articles matched the eligibility criteria. There were disparate methodologies and conflicting results, although they tended to indicate a decrease in blood-tumor barrier permeability, decreased tumoral perfusion, decreased tumoral diffusivity, and selleck the possibility of decreased perfusion in contralateral normal-appearing brain tissue.
CONCLUSION: Treatment with dexamethasone may alter imaging parameters from cerebral perfusion studies used in the management of brain tumors. In adequately powered studies, it may be possible to assess the longer term effects of dexamethasone on normal
brain tissue to help optimize use with longer term survivors that are emerging as improvements in glioma treatment are made.”
“Models of growth hormone (GH) rhythmogenesis which we and others have presented suggest that the GH pulses in the circulation are generated by a GH-releasing hormone (GHRH) oscillator with a 1 h periodicity. Here we examine the possibility that this is an intrinsic neuronal rhythm resulting from enzymatic reactions occurring in the axon terminals. A “”Baselator”" feedback reaction sequence can generate an hourly chemical burst of a primer (presumably
a low molecular weight peptide) regulating Ca(2+)-triggered exocytosis of CHAN-loaded vesicles. Accordingly we propose that the priming species is largely immobilized by binding within the terminals. Free unbound primer is able to diffuse and is alternately phosphorylated and dephosphorylated by a kinase and a phosphatase (or undergoes a similar pair of complementary reactions). Under appropriate conditions involving feedback control IPI-549 of one or other of the enzymes the levels of both unreacted and reacted free primer peak sharply at hourly intervals.
It is self-evident that synchronization between the packed terminals of the GHRH neurons at the median eminence is necessary to generate highly ordered in vivo pulses of GH release. Gap junctions provide a means of interterminal communication for the primer. Simulations of clusters of 4 adjacent axon terminals in a linear array were performed to assess whether and when synchrony can occur. With gap junctions closed the axons were set to be 90 degrees out of phase, i.e. their chemical bursts were separated by 15 min. Opening the gap junctions, assuming either that only the unphosphorylated species permeates, or that both species permeate, resulted in rapid overall synchronization.