Editorial comment

Building small things for small patients is tough, and sometimesexpensive, but it really needs to be done. I was pleased tosee the paper by Thierry Scohy et al., the Rotterdam PediatricCardiology, Anesthesiology and Surgery group, in a paper publishedin this issue of the European Journal of Echocardiography, asuitable venue for this report, since so much of the developmentof this device has been European. In this paper, the group reportstheir experience using a micromultiplane transesophageal probe     

Calcium mobilization and entry by thapsigargin in neuronal tumor cell line, SK-N-SH.

Using fura-2 loaded neural tumour cells, SK-N-SH, we demonstrate that receptor-mediated activation of phosphoinositide hydrolysis not only causes the release of Ca2+ from intracellular stores but also causes a concomitant influx of extracellular Ca2+. Thapsigargin (TG), a sesquiterpene lactone, causes a sustained elevation of intracellular Ca2+ and depletion of the inositol 1, 4, 5-trisphosphate-sensitive intracellular Ca2+ stores. In the absence of extracellular Ca2+, the increase in intracellular Ca2+ concentration ([Ca2+]i) was transient, suggesting that thapsigargin activates both intracellular mobilization and the influx of Ca2+ from extracellular space. These results are consistent with the proposal that the depletion of the inositol 1, 4, 5-trisphosphate-sensitive intracellular Ca2+ pool serves as a signal for Ca2+ influx.     

The metabolism of dopamine in the median eminence reflects the activity of tuberoinfundibular neurons

The purpose of the present study was to characterize the metabolism of dopamine (DA) in tuberoinfundibular (TI) neurons terminating in the median eminence and to examine the effects of procedures that alter the synthesis and turnover of DA in these neurons on the concentrations of dihydroxyphenylacetic acid (DOPAC) in the median eminence. The DA uptake inhibitor nomifensine (25 mg/kg, i.p.; 30 min) failed to alter median eminence DOPAC concentrations indicating that very little released DA is recaptured and metabolized by TIDA neurons. Within 5 min following the administration of the monoamine oxidase inhibitor pargyline (50 mg/kg, i.v.) median eminence DOPAC concentrations declined to 15% of control demonstrating that this metabolite has a high turnover rate and is rapidly removed from the median eminence. Median eminence DOPAC concentrations in diestrous female rats, whose TIDA neuronal activity is higher than in the male, were two-fold greater than in male rats. Prolactin (10 micrograms/rat, i.c.v.; 12 h), which increases TIDA neuronal activity, produced a corresponding increase in median eminence DOPAC concentrations in male rats. Restraint stress (30 min), which decreases TIDA neuronal activity, produced a corresponding decrease in median eminence DOPAC concentrations in diestrous female rats. The results from the present study suggest that DOPAC concentrations in the median eminence can be used as an index of TIDA neuronal activity.     

Diminished susceptibility to daptomycin accompanied by clinical failure in a patient with methicillin-resistant Staphylococcus aureus bacteremia.

We cared for a patient with methicillin-resistant Staphylococcus aureus bacteremia who experienced clinical failure with daptomycin. The failure was accompanied by progressive elevation of the daptomycin minimum inhibitory concentration during treatment. DNA fingerprinting confirmed that the minimum inhibitory concentration elevation occurred within the same strain of methicillin-resistant Staphylococcus aureus. This observation provides important new information to clinicians who adopt this promising drug for treatment of serious infections caused by methicillin-resistant Staphylococcus aureus.     

In vitro cytotoxicity of a remineralizing resin-based calcium phosphate cement.

Recently, a resin-based calcium phosphate cement (RCPC) has been reported as a remineralizing pulp-capping or lining cement. RCPC consists mainly of tetracalcium and dicalcium phosphates, ethoxylated bisphenol A dimethacrylate and pyromellitic glycerol dimethacrylate monomers and photo- and chemical initiators. OBJECTIVES: Here, the cytotoxic effects of RCPC were evaluated. The hypothesis was that RCPC induced only minor cytotoxic response in immortalized murine odontoblast and pulp cells, comparable to that produced by similar dimethacrylates due to unpolymerized dimethacrylate monomer present after curing. METHODS: Cytotoxicity was determined following the changes in cell succinate dehydrogenase activity after 24 h exposure to the cement components and after a 24 h recovery period. A fourfold range of concentrations was tested of the monomers, the eluate of cured RCPC leached in Dulbecco's modified Eagle's medium, and crushed cured cement in dimethyl sulfoxide. RESULTS: The monomers themselves had cytotoxicities similar to those reported for other dimethacrylates, although they are significantly less toxic than Bis-GMA. Differential cell sensitivity was demonstrated, with the pulp cells having greater sensitivity to the unpolymerized monomer than the odontoblast-like cells. The leached components have cytotoxicity similar to that of the free monomers. The crushed material demonstrated no apparent cytotoxicity at the dilutions tested. SIGNIFICANCE: These data demonstrate that RCPC has an in vitro cytotoxicity that is comparable to other materials containing dimethacrylate monomers and suggest that the material may be suitable for use in dental restorations. The data also indicate that the pulp cells appear more sensitive to dimethacrylates than the odontoblasts.     

Glutamate acts at NMDA receptors on fresh bovine and on cultured human retinal pigment epithelial cells to trigger release of ATP

Efficient vesicle membrane recycling at presynaptic terminals is pivotal for preventing depletion and maintaining high firing rates in neuronal networks. We used a new approach, based on the combination of spectrally different optical probes, to investigate how stimulation determines the fate of synaptic vesicles after endocytosis. We found that in the small central synapses of rat hippocampal neurones low frequency stimulation (40 action potentials at 2 Hz) targets vesicles preferentially to vesicle pools that were kinetically faster. Vesicles taken up during endocytosis triggered by high frequency stimulation (400 action potentials, 20 Hz) were also placed in the back of the release queue. We performed a spatial analysis of the recycled vesicles in living hippocampal boutons using two spectrally different FM-dyes (FM1-43 and FM5-95). By using these consecutively, vesicles endocytosed by either stimulation protocol were labelled with a different colour. This revealed that the kinetic arrangement was also reflected in the spatial organization of vesicles within the bouton. Next, we identified the postsynaptic site of the active zone by transfecting the neurones with postsynaptic density protein PSD-95-CFP. The data from these triple colour experiments suggest that retrieval after low frequency stimulation keeps vesicles in a more confined region closer to the active zone as identified by PSD-95-CFP expression at the postsynaptic site.