Neuronal D-serine and glycine release via the Asc-1 transporter regulates NMDA receptor-dependent synaptic activity.

D-Serine and glycine are coagonists of NMDA receptors (NMDARs), but their relative contributions for several NMDAR-dependent processes are unclear. We now report that the alanine-serine-cysteine transporter-1 (Asc-1) mediates release of both D-serine and glycine from neurons, and, in turn, this modulates NMDAR synaptic activity. Asc-1 antiporter activity is enhanced by D-isoleucine (D-Ile), which releases D-serine and glycine from Asc-1-transfected cells, primary neuronal cultures, and hippocampal slices. D-Ile has no effect on astrocytes, which do not express Asc-1. We show that D-Ile enhances the long-term potentiation (LTP) in rat and mouse hippocampal CA1 by stimulating Asc-1-mediated endogenous D-serine release. D-Ile effects on synaptic plasticity are abolished by enzymatically depleting D-serine or by using serine racemase knock-out (SR-KO) mice, confirming its specificity and supporting the notion that LTP depends mostly on D-serine release. Conversely, our data also disclose a role of glycine in activating synaptic NMDARs. Although acute enzymatic depletion of D-serine also drastically decreases the isolated NMDAR synaptic potentials, these responses are still enhanced by D-Ile. Furthermore, NMDAR synaptic potentials are preserved in SR-KO mice and are also enhanced by D-Ile, indicating that glycine overlaps with D-serine binding at synaptic NMDARs. Altogether, our results disclose a novel role of Asc-1 in regulating NMDAR-dependent synaptic activity by mediating concurrent non-vesicular release of D-serine and glycine. Our data also highlight an important role of neuron-derived D-serine and glycine, indicating that astrocytic D-serine is not solely responsible for activating synaptic NMDARs.

Epidural anesthesia as a novel anesthetic technique for anterior lumbar interbody fusion.

STUDY OBJECTIVE: To determine if epidural anesthesia is a reasonable technique for anterior lumbar interbody fusion. DESIGN: Retrospective chart review. SETTING: Academic university hospital. MEASUREMENTS: The charts of patients who underwent an anterior lumbar interbody fusion between January 1, 2001 and November 1, 2008 were reviewed. A total of 102 consecutive patients, of whom 19 received an epidural and 83 underwent general anesthesia, met inclusion criteria. Postoperative pain, nausea, opioid administration, operating room time, anesthesia time, Postanesthesia Care Unit (PACU) time, and total hospital time were compared. MAIN RESULTS: In the PACU, patients receiving epidural anesthesia showed reductions in median immediate [numerical rating scale (NRS) 0 vs 7; P < 0.001] and peak (NRS 4 vs 8; P = 0.001) postoperative pain scores, and postoperative mean arterial pressure (69.7 vs 90.3; P < 0.001). Epidural anesthesia patients also needed significantly less intravenous morphine-equivalent medication both intraoperatively (5 vs 29; P < 0.001) and postoperatively (3.34 vs 10; P = 0.021). CONCLUSIONS: Epidural anesthesia for anterior lumbar interbody fusion is potentially beneficial compared with general anesthesia, showing improved perioperative pain control.

Renal dialysis in Barbados - part 1: cost of dialysis provision at the Queen Elizabeth Hospital

OBJECTIVE: The purpose of this study was to assess the health service cost of haemodialysis delivered by the Queen Elizabeth Hospital, Barbados. DESIGN AND METHODS: A cost analysis was performed from the viewpoint of the study hospital using the treatment protocols based on current practice. These incorporated procedures to establish dialysis access sites (surgical set up) and dialysis maintenance. Cost and patient data were collected for the period April 1, 1998 to March 31, 1999. Sixty-four patients were studied. Analyzed costs included personnel, drug expenditure, supplies (dialysis and non-dialysis related), inpatient costs, laboratory and other ancillary services, and indirect or overhead costs such as plant, housekeeping, laundry and administration. RESULTS: The final cost per patient year was $37,930.04 in the first year of dialysis and included surgical set-up, and $34,059.08 in the subsequent years (excluding inpatient admissions and treatments for complications). The total cost of dialysis provision for the year excluding surgical set up was $2,178,561.09. The cost per visit was estimated to be $286.95. Direct costs (determined by patient utilization and physician and nurse directives) amounted to 81.8 percent of total cost. The main expenditure sections were dialysis-related supplies, labour and overheads. Cost savings incurred as a result of strict modification of treatment guidelines were estimated. By altering the number of dialysis visits per week and introducing other cost saving measures, such as dialyzer re-use, a savings of $852,176.32 was observed with a full potential savings of $902,218.63. An incremental cost analysis of a service expansion (scenario 1) indicated that the cost savings would be sufficient to provide an additional 3,328 dialysis treatments or visits per year, incorporating 4 additional dialysis machines. CONCLUSIONS: These findings are important in the light of constrained economic resources. However, the outcomes associated with the observed costs must be explored in order to assess the "true value" or cost effectiveness of the current dialysis practice. Therefore, this analysis is but one component of an overall study to review the renal dialysis services in Barbados for the purpose of informing plans for expansion and optimization of services.(Au)