PubMed · 14935060
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
E F EVERITT. 1952. Vinyl ether.. https://doi.org/10.1093/bja%2F24.3.201
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
"Free Zn2+" (rapidly exchangeable Zn2+) is stored along with glutamate in the presynaptic terminals of specific specialized (gluzinergic) cerebrocortical neurons. This synaptically releasable Zn2+ has been recognized as a potent modulator of glutamatergic transmission and as a key toxin in excitotoxic neuronal injury. Surprisingly (despite abundant work on bound zinc), neither the baseline concentration of free Zn2+ in the brain nor the presumed co-release of free Zn2+ and glutamate has ever been directly observed in the intact brain in vivo. Here, we show for the first time in dialysates of rat and rabbit brain and human CSF samples from lumbar punctures that: (i) the resting or "tonic" level of free Zn2+ signal in the extracellular fluid of the rat, rabbit and human being is approximately 19 nM (95% range: 5-25 nM). This concentration is 15,000-fold lower than the "300 microM" concentration which is often used as the "physiological" concentration of free zinc for stimulating neural tissue. (ii) During ischemia and reperfusion in the rabbit, free zinc and glutamate are (as has often been presumed) released together into the extracellular fluid. (iii) Unexpectedly, Zn2+ is also released alone (without glutamate) at a variable concentration for several hours during the reperfusion aftermath following ischemia. The source(s) of this latter prolonged release of Zn2+ is/are presumed to be non-synaptic and is/are now under investigation. We conclude that both Zn2+ and glutamate signaling occur in excitotoxicity, perhaps by two (or more) different release mechanisms.
L-glutamate (Glu) is the predominant excitatory neurotransmitter in the mammalian central nervous system. It plays major roles in normal neurophysiology and many brain disorders by binding to membrane-bound Glu receptors. To overcome the spatial and temporal limitations encountered in previous in vivo extracellular Glu studies, we employed enzyme-coated microelectrode arrays to measure both basal and potassium-evoked release of Glu in the anesthetized rat brain. We also addressed the question of signal identity, which is the predominant criticism of these recording technologies. In vivo self-referencing recordings demonstrated that our Glu signals were both enzyme- and voltage-dependent, supporting the identity of L-glutamate. In addition, basal Glu was actively regulated, tetrodotoxin (TTX)-dependent, and measured in the low micromolar range (approximately 2 microm) using multiple self-referencing subtraction approaches for identification of Glu. Moreover, potassium-evoked Glu release exhibited fast kinetics that were concentration-dependent and reproducible. These data support the hypothesis that Glu release is highly regulated, requiring detection technologies that must be very close to the synapse and measure on a second-by-second basis to best characterize the dynamics of the Glu system.
To assess the genotoxicity of 14 chemical agents used as locally applied agents in dental practice, the ability of these agents to elicit chromosome aberrations was examined using Syrian hamster embryo (SHE) cells. Chromosome aberrations in SHE cells were induced by treatment with three of eight chemical agents used as endodontic medicaments, i.e. ethylenediaminetetraacetic acid (EDTA), formocresol (a mixture of formalin and tricresol), and sodium arsenite. The other five chemical agents, i.e. chloramphenicol, p-chlorophenol, p-phenolsulfonic acid, sodium hypochlorite, and tetracycline hydrochloride exhibited a negative response for chromosome aberrations. Assessment of three dyes used for disclosing dental plaque showed chromosome aberrations induced by basic fuchsin but not by acid fuchsin and erythrosine B. Three local anesthetics, lidocaine hydrochloride, prilocaine hydrochloride, and procaine hydrochloride, were negative for chromosome aberrations. Among the ten chemical agents that exhibited a negative response in the assay, p-chlorophenol, sodium hypochlorite, and erythrosine B induced chromosome aberrations in SHE cells when treated in the presence of exogenous metabolic activation. The percentages of cells with polyploidy or endoreduplication were enhanced by formocresol, sodium arsenite, p-chlorophenol, p-phenolsulfonic acid, sodium hypochlorite, erythrosine B, prilocaine hydrochloride, and procaine hydrochloride in the absence or presence of exogenous metabolic activation. Our results indicate that the chemical agents that had a positive response in the present study are potentially genotoxic to mammalian cells.