Background: Sevoflurane undergoes Baralyme- or soda lime-catalyzed degradation in the anesthesia circuit to yield compound A (2-[fluoromethoxy]-1,1,3,3,3-pentafluoro-1-propene), which is nephrotoxic in rats and undergoes metabolism via the cysteine conjugate beta-lyase pathway in those animals. The objective of these experiments was to test the hypothesis that compound A undergoes beta-lyase-dependent metabolism in humans.
Methods: Human volunteers were anesthetized with sevoflurane (1.25 minimum alveolar concentration, 3%, 2 l/min, 8 h) and thereby exposed to compound A. Urine was collected at 24-h intervals for 72 h after anesthesia. Rats, which served as a positive control, were given compound A intraperitoneally, and urine was collected for 24 h afterward. Human and rat urine samples were analyzed by19 F nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry for the presence of compound A metabolites.
Results: Analysis of human and rat urine showed the presence of the compound A metabolites [S-[2-(fluoromethoxy)-1,1,3,3,3-pentafluoropropyl]-N-acetyl-L-cysteine, (E)- and (Z)-S-[2-(fluoromethoxy)-1,3,3,3-tetrafluoro-1-propenyl]-N-acetyl-L-cyst eine, 2-(fluoromethoxy)-3,3,3-trifluoropropanoic acid, 3,3,3-trifluorolactic acid, and inorganic fluoride. The presence of 2-(fluoromethoxy)-3,3,3-trifluoropropanoic acid and 3,3,3-trifluorolactic acid in human urine was confirmed by gas chromatography-mass spectrometry. 相似文献
Primary sensory neurons can generate irregular burst firings in which the existence of significant deterministic behaviors of chaotic dynamics has been proved with nonlinear time series analysis. But how well the deterministic characteristics and neural information of presynaptic chaotic spike trains were transmitted into postsynaptic spike trains is still an open question. Here we investigated the synaptic transmission of chaotic spike trains between primary Adelta afferent fiber and spinal dorsal horn neuron. Two kinds of basic stimulus unit, brief burst and single pulse, were employed by us to comprise chaotic stimulus trains. For time series analysis, we defined "events" as the longest sequences of spikes with all interspike intervals less than or equal to a certain threshold and extracted the interevent intervals (IEIs) from spike trains. Return map analysis of the IEI series showed that the main temporal structure of chaotic input trains could be detected in postsynaptic output trains, especially under brief-burst stimulation. Using correlation dimension and nonlinear prediction methods, we found that synaptic transmission could influence the nonlinear characteristics of chaotic trains, such as fractal dimension and short-term predictability, with greater influence made under single-pulse stimulation. By calculating the mutual information between input and output trains, we found the information carried by presynaptic spike trains could not be completely transmitted at primary afferent synapses, and that brief bursts could more reliably transmit the information carried by chaotic input trains across synapses. These results indicate that although unreliability exists during synaptic transmission, the main deterministic characteristics of chaotic burst trains can be transmitted across primary afferent synapses. Moreover, brief bursts that come from the periphery can more reliably transmit neural information between primary afferent fibers and spinal dorsal horn neurons. 相似文献
The dominant cone-rod dystrophy gene CORD6 has previously been mapped to
within an 8 cM interval on chromosome 17p12-p13. The retinal- specific
guanylate cyclase gene (RETGC-1), which maps to within this genetic
interval and previously was implicated in Leber's congenital amaurosis, was
screened for mutations within this family and in a panel of small families
and individuals with various cone and cone- rod dystrophy phenotypes. A
missense mutation (E837D) was identified in affected members of the CORD6
family, as well as a second missense mutation (R838C) in three other
families with dominant cone-rod dystrophy. RETGC-1 is only the fourth gene
to be implicated in cone-rod dystrophy and this is the first report of
dominant mutations in this gene.
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