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991.
Victor W. Pike Christer Halldin Julie A. McCarron Camilla Lundkvist Ella Hirani Hans Olsson Susan P. Hume Per Karlsson Safiye Osman Carl-Gunnar Swahn Håkan Hall Håkan Wikström Marguerite Mensonidas Keith G. Poole Lars Farde 《European journal of nuclear medicine and molecular imaging》1998,25(4):338-346
[carbonyl-11C]Desmethyl-WAY-100635 (DWAY) is possibly a low-level metabolite appearing in plasma after intravenous administration of [carbonyl-11C]WAY-100635 to human subjects for positron emission tomographic (PET) imaging of brain 5-HT1A receptors. In this study we set out to assess the ability of DWAY to enter brain in vivo and to elucidate its possible interaction
with 5-HT1A receptors. Desmethyl-WAY-100635 was labelled efficiently with carbon-11 (t
1/2 = 20.4 min) in high specific radioactivity by reaction of its descyclohexanecarbonyl analogue with [carbonyl-11C]cyclohexanecarbonyl chloride. The product was separated in high radiochemical purity by high-performance liquid chromatography
(HPLC) and formulated for intravenous injection. Rats were injected intravenously with DWAY, sacrificed at known times and
dissected to establish radioactivity content in brain tissues. At 60 min after injection, the ratios of radioactivity concentration
in each brain region to that in cerebellum correlated with previous in vitro and in vivo measures of 5-HT1A receptor density. The highest ratio was about 22 in hippocampus. Radioactivity cleared rapidly from plasma; HPLC analysis
revealed that DWAY represented 55% of the radioactivity in plasma at 5 min and 33% at 30 min. Only polar radioactive metabolites
were detected. Subsequently, a cynomolgus monkey was injected intravenously with DWAY and examined by PET. Maximal whole brain
uptake of radioactivity was 5.7% of the administered dose at 5 min after injection. The image acquired between 9 and 90 min
showed high radioactivity uptake in brain regions rich in 5-HT1A receptors (e.g. frontal cortex and neocortex), moderate uptake in raphe nuclei and low uptake in cerebellum. A transient
equilibrium was achieved in cortical regions at about 60 min, when the ratio of radioactivity concentration in frontal cortex
to that in cerebellum reached 6. The corresponding ratio for raphe nuclei was about 3. Radioactive metabolites appeared rapidly
in plasma, but these were all more polar than DWAY, which represented 52% of the radioactivity in plasma at 4 min and 20%
at 55 min. In a second PET experiment, in which a cynomolgus monkey was pretreated with the selective 5-HT1A receptor antagonist, WAY-100635, at 25 min before DWAY injection, radioactivity in all brain regions was reduced to that
in cerebellum. Autoradiography of post mortem human brain cryosections after incubation with DWAY successfully delineated
5-HT1A receptor distribution. Receptor-specific binding was eliminated in the presence of the selective 5-HT1A receptor agonist, 8-OH-DPAT [(±)-8-hydroxy-2-dipropylaminotetralin]. These findings show that: (a) intravenously administered
DWAY is well able to penetrate brain in rat and monkey, (b) DWAY is a highly effective radioligand for brain 5-HT1A receptors in rat and monkey in vivo and for human brain in vitro, and (c) the metabolism and kinetics of DWAY appear favourable
to successful biomathematical modelling of acquired PET data. Thus, DWAY warrants further evaluation as a radioligand for
PET studies of 5-HT1A receptors in human brain.
Received 1 October and in revised form 12 December 1997 相似文献
992.
993.
Step-down heating (SDH) was investigated in mouse testis by giving an initial treatment of 3 min at 43.0 degrees C followed immediately by a treatment in the temperature range 38.0-42.0 degrees C. The dose-response curves for testis weight loss as a function of duration of hyperthermia were compared with those obtained using single-temperature treatments. In all cases the curves were linear, allowing the use of Arrhenius analysis. For single-temperature treatments the Arrhenius relationship showed an inflection at approximately 41 degrees C with a small, but significant, increase in activation energy for hyperthermal temperatures below the transition. SDH increased the thermal sensitivity in this lower range, by approximately 1 degree C, but the activation energy was not significantly altered. The results support the view that in vivo thermosensitization by SDH is not due solely to inhibition of development of thermotolerance. 相似文献
994.
Reassessment of changes in leucocyte and serum ascorbic acid after acute myocardial infarction.
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After an acute myocardial infarction, there is an apparent acute fall in leucocyte ascorbic acid associated with an acute rise in white blood cells and serum cortisol. The apparent fall in leucocyte ascorbic acid is the result of the granulocytosis which occurs after the infarction. Estimations of ascorbic acid disclose that the granulocyte contains approximately half the ascorbic acid of the lymphocyte. When the granulocytosis subsides, the new population of white blood cells is depleted of ascorbic acid for at least 56 days, reflecting tissue desaturation which can be corrected by ascorbic acid supplements. Tissue desaturation is also reflected in subnormal serum ascorbic acid levels which persist also unless ascorbic acid supplements are given. Observations on normal subjects given infusions of tetracosactrin (Synacthen) show that adrenal stimulation can produce a similar rise in white blood cells and an apparent fall in leucocyte ascorbic acid concentration with the exception that the serum ascorbic acid remains unaltered. Therefore, while adrenal stimulation can mimic 'stress' with regard to the changes in the white blood cells, tissue depletion of ascorbic acid as reflected in the white blood cells and serum after a myocardial infarction requires a focus of damaged tissue. 相似文献
995.
996.
997.
William J. Hume 《Journal of dentistry》1975,3(1):25-43
A review of geographic stomatitis and an assessment of the opinions and clinical records which have been published concerning this common and often ignored condition are presented. 相似文献
998.
999.
Expected hemotherapy in elective surgery. A follow-up. 总被引:1,自引:0,他引:1
Preoperative cross match guidelines were developed from a review of elective surgical hemotherapy. Six elective surgical procedures were studied prospectively to determine the effectiveness of the recommendations. All six procedures demonstrated a substantial reduction in preoperative cross match ordering during the study period, although for only one procedure was the guidelines' recommendation followed strictly. For those procedures that rarely required hemotherapy, an ABO-Rh typing and an antibody detection test were recommended as a preoperative study without a cross match. Through education of the clinical staff, successful establishment of these guidelines can lead to substantial monetary savings, reduced blood outdating, and a decreased blood bank workload with a more appropriate allocation of the technologists' time and effort. 相似文献
1000.
Seventeen male patients with chronic obstructive airways disease in remission were separated into two groups according to arterial carbon dioxide tensions. Hypercapnia was associated significantly with hypoxia and increased red cell volume whereas normocapnia was not. Normocapnic patients were significantly lighter than those with hypercapnia. Total body potassium (TBK) measured by the whole body monitor was significantly low in two of the patients studied (P less than 0.005). The mean value for TBK for the normocapnic group as a whole was significantly low (P less than 0.005), but the mean value for the hypercapnic group was not. Serum potassium and erythrocyte potassium concentrations were normal even when TBK was low, and diuretics had no apparent influence on these potassium values. Of four patients (two in the series and two others) who had TBK measured after a recent episode of cor pulmonale, three had significantly low values. The only previous studies using a whole body monitor to measure TBK in chronic obstructive airways disease found no such low values, though other workers estimating exchangeable potassium by isotope dilution techniques had found evidence of gross potassium depletion. It is concluded that low TBK does indeed occur in patients with chronic obstructive airways disease and that gross depletion is more likely to follow an episode of cor pulmonale. 相似文献