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81.
The effect of probenecid on the pharmacokinetics of diflunisal and its glucuronide and sulphate conjugates was studied in 8 healthy volunteers. Diflunisal 250 mg b. d. was administered p. o. for 15 days and its steady state pharmacokinetics was evaluated on Day 16 after the last dose (control phase). Probenecid 500 mg b. d. was co-administered throughout the entire study period in the treatment phase of the study.The steady state plasma concentration of diflunisal was significantly higher during the probenecid treatment phase as compared to the control phase (104.0 vs. 63.1 g·ml–1). This was the result of a significant decrease in the plasma clearance of diflunisal from 5.8 (control) to 3.4 ml·min–1 (probenecid co-administration). The metabolite formation clearances of both glucuronides were significantly decreased by probenecid, -45 % and -54 % for the phenolic and acyl glucuronide, respectively. The metabolite formation clearance of the sulphate conjugate was not affected by probenecid co-administration.Steady state plasma concentrations of the sulphate and glucuronide conjugates of diflunisal were 2.5- to 3.1-fold higher during probenecid co-administration, due to a significant reduction in the renal clearance of the three diflunisal conjugates. Probenecid also reduced the plasma protein binding of diflunisal, but only to a minor extent; the unbound plasma fraction of diflunisal at steady state averaged between 5 and 30 % higher during probenecid co-administration.  相似文献   
82.
目的:探讨闭角型青光眼患者凝血指标变化与临床的关系。方法:对50例闭角型青光眼患者及43例正常对照组进行了凝血指标(PT、TT、Fbg、APTT)检测。结果:闭角型青光眼患者与对照组比较PT、TT无显著变化(P<0.05),Fbg含量升高有极显著性差异(P<0.01),APTT时间缩短有极显著性差异(P<0.01)。结论:闭角型青年眼患者体内血液是高凝状态,而这种高凝状态在闭角青光眼病的发生、发展中起着重要的作用。  相似文献   
83.
Since our major hypothesis is that prenatal protein malnutrition significantly affects hippocampal neuroplasticity, this study examined the effects of prenatal protein malnutrition on the modulation of dentate granule cell excitability in freely moving rats at 15, 30 and 90 days of age across the vigilance states of quiet waking (QW), slow-wave sleep (SWS) and rapid eye movement (REM) sleep. Using paired-pulse stimulation, the paired-pulse index (PPI), a measure of the type and degree of modulation of dentate granule cell excitability elicited by stimulation of the medial perforant path, was obtained for each vigilance state at each stage of development. Four specific measures of granule cell excitability were computed, namely, PPI using both population spike amplitude (PSA) and EPSP slope measures, absolute values of PSA(1) and EPSP(1) slope. PPI values obtained at 15, 30 and 90 days of age, however, were altered during normal ontogenetic development, but not by vigilance state. At 15 days of age, the malnourished group exhibits greater early inhibition of the PPI using the PSA measure at IPIs between 20 and 30 ms regardless of vigilance state, while at 30 days of age, the malnourished group exhibits greater facilitation at IPIs between 50 and 70 ms during QW and SWS, but not during REM sleep. In the control adult (PND90) and juvenile (PND30) animal, PSA(1) values are significantly higher during SWS than in QW or REM sleep. However, for the younger malnourished animals (PND15 and PND30), PSA(1) values were found to be significantly greater during REM sleep rather than SWS. Therefore, as the animal matures, there appears to be a shift in vigilance state dependent synaptic transmission through the hippocampal trisynaptic circuit from REM sleep to SWS in both control and malnourished animals, with the change occurring later in malnourished animals when compared to control ones. Furthermore, our findings suggests that prenatal protein malnutrition significantly alters modulation of dentate granule cell excitability (i.e., PPI values using the PSA measure) during the earlier stages of development but not in adulthood.  相似文献   
84.
对862例心血管疾病介入诊治术患者术前分别采用心理护理(n=431)和非心理护理(n=431)前后比较心理状态差别观察。结果显示:手术前所有患者均有严重焦虑心理,经采用心理宣教、心理护理后,患者焦虑程度大大降低(P<0.001),处于接受手术的最佳心理状态,保证手术顺利进行,并减少了术前、中、后并发症的发生。而未行心理宣教及心理护理的患者的焦虑程度几乎没有变化(P>0.05),有的甚至提高。通过对照观察、心理宣教及心理护理的有效实施,对消除患者的焦虑、恐惧心理有较满意的效果,并能达到仅靠操作技术难以获得的效果,起到良好的助手作用。  相似文献   
85.
Different features of visual function mature along unique timescales through infancy and early childhood. It is not clear which functions continue to mature in school age children. Functions believed to be mediated by the Magnocellular (M) and Parvocellular (P) pathways were compared in five- (n=25), eight- (n=21) and eleven-year-old children (n=21) and young adult controls (n=20). Steady-state visual evoked potentials were recorded from occipital electrodes in response to very low spatial frequency gratings, at a series of contrasts (M), and to high contrast gratings at a series of spatial frequencies (P). No evidence was found to indicate M pathway development across these age groups. However, the youngest children demonstrated elevated VEP thresholds to the high contrast gratings compared with either the adults or eleven-year-olds. This difference in threshold implies an immaturity of the high contrast, high spatial frequency stream, i.e. the putative P pathway. This revised version was published online in July 2006 with corrections to the Cover Date.  相似文献   
86.
Purpose. A QSAR study based on electrotopological state (E-state) indices was conducted for a series of flavone HIV-1 integrase inhibitors to guide drug design. Methods. E-state indices formulated to encode electronic and topological information for each skeletal atom in a molecule (Kier and Hall Pharm. Res. 7:801–807 (1990)) were calculated using the Molconn-X program, and partial least squares (PLS) multivariate regression was used to derive QSAR models. Results. Predictive models with correlation coefficients (r2) of 0.98 (3 PLS components) and 0.99 (5 PLS components) and corresponding cross-validated correlation coefficients (c.v. r2) of 0.51 and 0.73, were obtained for inhibition of cleavage and integration, respectively, with one molecule omitted from the analysis. Conclusions. E-state indices at C6, C3, C5, C5, and O4 were found to be more important for prediction of activity than those for any of the other 12 flavone skeletal atoms that are common to the molecules in the data set.  相似文献   
87.
The refractive state of the eye of the South American opossum Didelphis marsupialis aurita was investigated with electrophysiological techniques. Using adult specimens, trapped from the wild, averaged cortical evoked responses were recorded from the region of projection of the central visual field. Stimuli consisted of a phase reversal of a square wave grating generated on a CRO screen, with luminance of 2.4 cd/m2 and contrast 0.84. The refractive state of the eye was altered by means of trial lenses and the amplitude of the cortical responses thus obtained compared to those obtained with no lens (control values). Refraction "tuning curves" were determined for each animal. The average refractive state was found to be -2.27 D indicating that this species when raised in its habitat shows, at low ambient luminosity, some degree of myopia. Determination of the Contrast Sensitivity Function indicate that induced ametropias lead to a reduction of the cut-off value of the spatial frequency and a loss of contrast sensitivity.  相似文献   
88.
Effect on electroencephalogram of chewing flavored gum   总被引:3,自引:0,他引:3  
The objective of the present study was to evaluate the effect on the electroencephalogram (EEG) of a chewing gum with and without our prepared new flavor. Electroencephalograms were obtained after the following three tests: chewing pure gumbase with sucrose (standard gumbase), chewing flavored standard gum and the inhalation of flavored aromatic oil. As the control, we used the pre-stimulus control EEG record without a stimulus. We examined the relationship between the pre-stimulus control record and the post-stimulus record using the changes of power in four bands. Chewing the standard gumbase led to an increase in the alpha wave and a decrease in the beta wave. Chewing the flavored standard gum and inhaling the flavored aromatic oil each increased the alpha and beta waves. In addition, chewing the flavored standard gum led to a change in the ratio of theta wave in the frontal area. The difference in the theta, alpha and beta bands in chewing gum with and without the added flavor suggested that the flavor as well as chewing could induce concentration with a harmonious high arousal state in brain function.  相似文献   
89.
Objective assessment of auditory thresholds in noise‐induced hearing loss using steady‐state evoked potentials The purpose of this study is to evaluate whether steady‐state evoked potential (SSEP) can be used for objective estimation of auditory thresholds in patients with noise‐induced hearing loss (NIHL). Eleven subjects (22 ears) with a characteristic audiometric notch between 3000 and 6000 Hz participated in this study. Both pure‐tone thresholds and SSEP thresholds were obtained for each ear of all subjects. The correlation of SSEP thresholds and pure‐tone thresholds was assessed. The results show that SSEP thresholds predicted pure‐tone thresholds with correlation coefficients (r) of 0.86, 0.92, 0.94 and 0.95 at 500, 1000, 2000 and 4000 Hz respectively. Typically, the SSEP thresholds overestimate the pure‐tone thresholds by 10–20 dB, but they closely reflect the configuration of the audiogram. The strength of the relationship between SSEP and pure‐tone thresholds increased with increasing frequency and increasing degree of hearing loss. In conclusion, SSEP can be used as a reliable and objective tool to assess auditory thresholds in patients with noise‐induced hearing loss with high‐frequency dips.  相似文献   
90.
Abstract: Botulinum neurotoxin (BoNT) metalloproteases and related proteases are the most selective proteases known. X‐ray crystal structures suggest that the active sites of the native enzymes exist in catalytically incompetent forms that must be activated by substrate binding. In order to characterize the postulated substrate‐induced conformational changes for enzyme activation, we synthesized a series of transition‐state analog inhibitors in which the dipeptide cleavage site is replaced by tetrahedral intermediate analogs within the minimal substrate peptide sequence. In this paper, we report our efforts to design inhibitors of BoNT/A metalloprotease. We confirm that an effective substrate sequence for BoNT/A metalloprotease is a 17‐mer peptide corresponding to residues 187–203 of SNAP‐25. A more stable substrate, Nle202SNAP‐25 [187–203] was synthesized in order to develop an assay for proteolytic activity of BoNT/A metalloprotease that can be used to monitor time‐dependent inhibition. α‐Thiol amide analogs of Gln‐197 were incorporated via solid‐phase peptide synthesis into both 17‐mer minimal peptide substrate sequences. The synthesis, characterization and inhibition kinetics for the α‐thiol amide analogs of holotoxin A substrate are described. These substrate‐derived inhibitors were shown to be submicromolar inhibitors of BoNT/A catalytic activity.  相似文献   
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