Zinc enhances hippocampal long-term potentiation at CA1 synapses through NR2B containing NMDA receptors.

The role of zinc (Zn2+), a modulator of N-methyl-D-aspartate (NMDA) receptors, in regulating long-term synaptic plasticity at hippocampal CA1 synapses is poorly understood. The effects of exogenous application of Zn2+ and of chelation of endogenous Zn2+ were examined on long-term potentiation (LTP) of stimulus-evoked synaptic transmission at Schaffer collateral (SCH) synapses in field CA1 of mouse hippocampal slices using whole-cell patch clamp and field recordings. Low micromolar concentrations of exogenous Zn2+ enhanced the induction of LTP, and this effect required activation of NMDA receptors containing NR2B subunits. Zn2+ elicited a selective increase in NMDA/NR2B fEPSPs, and removal of endogenous Zn2+ with high-affinity Zn2+ chelators robustly reduced the magnitude of stimulus-evoked LTP. Taken together, our data show that Zn2+ at physiological concentrations enhances activation of NMDA receptors containing NR2B subunits, and that this effect enhances the magnitude of LTP.

On-site pharmacists in the ED improve medical errors.

OBJECTIVE: The objective of the study was to compare errors in the emergency department (ED) with pharmacists present (PPs) for resuscitations and traumas vs with pharmacists absent (PAs). Our hypothesis was that errors would be significantly fewer during PP than PA times. We also hypothesized that times with PP would affect patients greater when disposition was to more critical areas (intensive care unit, or ICUs). METHODS: The study was conducted during a 3-month period in 2009 in a level 1 trauma center with an emergency medicine residency. This was a cross-sectional cohort study comparing a prospective analysis of patients during the time (10 hour/day) with PP and a retrospective review of the time on the same days (14 hours/day) with PA. Demographics of age, race, and sex were recorded. Patient disposition was either ICU, operating room, non-ICU wards, observation unit, or discharge. Main outcome was errors recorded including medications given but not ordered, medication ordered but not given, and time delays for medications. For demographics and prevalence, descriptive statistics and percentages were used. Percent differences and 95% confidence intervals (CIs) and χ2 were derived. Logistic regression used predictor variables of age, race, sex, disposition, and presence or absence of pharmacists. An a priori power analysis was performed. The study was powered at 80% with 186 subjects per group (PP vs PA), to find a difference of 20% between the 2 groups in percent of medical errors. RESULTS: There were 694 patients included in the 3-month period. A total of 242 presented during PP times and 452 during PA times. There were 383 (55%) male, 301 (43%) female, and 10 (2%) unknown sex. Mean age was 45±18 years in PP group and 48±20 years in PA group (P, nonsignificant). There was no difference in ethnicity between groups. There were 6 (3%) patients with errors recorded during PP times and 137 (30%) with errors recorded during PA times (difference, 27%; 95% CI, 23-32). Controlling for age, race, sex, and disposition, medical errors were 13.5 times more likely during PA than during PP times (adjusted odds ratio, 13.5; 95% CI, 5.7-31.9). CONCLUSION: With pharmacists absent, over 13 times more errors are recorded in our ED than with pharmacists present. An on-site pharmacist in the ED may be helpful in reducing medical errors.

Delirium in the course of cancer treatment.

Delirium is a frequent complication of cancer treatment and is associated with a high incidence of morbidity and mortality. This article summarizes recent literature on the epidemiology, mechanisms, and treatment of delirium in the patient with cancer. As data continue to emerge on risk factors and pathophysiological mechanisms, recognition of the distinctive features of delirium in specific cancer populations could contribute to a better understanding of consciousness, cognition, perception, and behavior during medical illness.

Behavioral and neurochemical effects of 5-(4-[4-(5-Cyano-3-indolyl)-butyl)-butyl]-1-piperazinyl)-benzofuran-2-carboxamide (EMD 68843): a combined selective inhibitor of serotonin reuptake and 5-hydroxytryptamine(1A) receptor partial agonist.

5-(4-[4-(5-Cyano-3-indolyl)-butyl)-butyl]-1-piperazinyl)-benzofuran-2-carboxamide (EMD 68843; vilazodone) is a novel compound with combined high affinity and selectivity for the 5-hydroxytryptamine (5-HT) transporter and 5-HT(1A) receptors. EMD 68843 was tested as a prototype compound, which benefits from dual pharmacological effects that could increase extracellular 5-HT to levels higher than those produced by conventional selective serotonin reuptake inhibitors (SSRIs). In Sf9 cells, EMD 68843 increased guanosine 5'-O-(3-[(35)S]thiotriphosphate) binding to 69% of the magnitude of the full 5-HT(1A) receptor agonist R-(1)-trans-8-hydroxy-2-[N-n-propyl-N-(39-iodo-29-propenyl)] aminotetralin (8-OH-PIPAT), indicating that it is a partial agonist at 5-HT(1A) receptors. Acute, systemic administration of EMD 68843 produced a larger maximal increase of extracellular 5-HT than the SSRI fluoxetine in both the ventral hippocampus (HPv) (558 versus 274%) and the frontal cortex (FC) (527 versus 165%). Regional differences in the response to the two drugs were also observed. These effects may be attributed to the differential regulation of 5-HT release in the HPv and FC by 5-HT(1A) autoreceptors. When challenged with the 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), EMD 68843-induced increases in extracellular 5-HT were greatly reduced in the HPv but to a lesser extent in the FC. In behavioral studies, EMD 68843 produced antidepressant-like effects in the forced swimming test in both rats and mice but only within a narrow dosage range. Like fluoxetine, EMD 68843 did not produce the symptoms of the 5-HT behavioral syndrome in rats but, unlike fluoxetine, pretreatment with EMD 68843 blocked expression of the 5-HT behavioral syndrome induced by 8-OH-DPAT. Taken together, the results show that EMD 68843 augments extracellular 5-HT levels in forebrain regions to a greater extent than fluoxetine. At higher doses, however, weak efficacy of EMD 68843 at postsynaptic 5-HT(1A) receptors may inhibit the expression of rodent antidepressant-like behaviors.