18F-FCWAY (18F-trans-4-fluoro-N-(2-[4-(2-methoxyphenyl) piperazin-1-yl)ethyl]-N-(2-pyridyl)cyclohexanecarboxamide) is useful in clinical research with PET for measuring serotonin 1A (5-HT1A) receptor densities in brain regions of human subjects but has significant bone uptake of radioactivity due to defluorination. The uptake of radioactivity in skull compromises the accuracy of measurements of 5-HT1A receptor densities in adjacent areas of brain because of spillover of radioactivity through the partial-volume effect. Our aim was to demonstrate with a rat model that defluorination of 18F-FCWAY may be inhibited in vivo to improve its applicability to measuring brain regional 5-HT1A receptor densities. METHODS: PET of rat head after administration of 18F-FCWAY was used to confirm that the distribution of radioactivity measured in brain is dominated by binding to 5-HT1A receptors and to reveal the extent of defluorination of 18F-FCWAY in vivo as represented by radioactivity (18F-fluoride ion) uptake in skull. Cimetidine, diclofenac, and miconazole, known inhibitors of CYP450 2EI, were tested for the ability to inhibit defluorination of 18F-FCWAY in rat liver microsomes in vitro. The effects of miconazole treatment of rats on skull radioactivity uptake and, in turn, its spillover on brain 5-HT1A receptor imaging were assessed by PET with venous blood analysis. RESULTS: PET confirmed the potential of 18F-FCWAY to act as a radioligand for 5-HT1A receptors in rat brain and also revealed extensive defluorination. In rat liver microsomes in vitro, defluorination of 18F-FCWAY was almost completely inhibited by miconazole and, to a less extent, by diclofenac. In PET experiments, treatment of rats with miconazole nitrate (60 mg/kg intravenously) over the 45-min period before administration of 18F-FCWAY almost obliterated defluorination and bone uptake of radioactivity. Also, brain radioactivity almost doubled while the ratio of radioactivity in receptor-rich ventral hippocampus to that in receptor-poor cerebellum almost tripled to 14. The plasma half-life of radioligand was also extended by miconazole treatment. CONCLUSION: Miconazole treatment, by eliminating defluorination of 18F-FCWAY, results in effective imaging of brain 5-HT1A receptors in rat. 18F-FCWAY PET in miconazole-treated rats can serve as an effective platform for investigating 5-HT1A receptors in rodent models of neuropsychiatric conditions or drug action. 相似文献
This paper reports the prevalence of chronic esophagitis and nutritional status among 538 young persons aged 15 to 26 years from the high risk area for esophageal cancer. Of these subjects, 166 were from households with history of esophageal cancer and 372 were from households without history of esophageal cancer. The Incidences of chronic esophagltis among male and female adolescents were 37. 6% and 36% respectively, which was significantly higher than those in the low risk area (17%). The frequency of chronic esophagltis in the adolescents in the households with history of esophageal cancer was aiso higher than in those In the households without history of esophageal cancer. The deficiencies of vitamins, especially of riboflavin and ascorbate, are prevalent and severe among these adolescents. Ascorbate deficiency Is correlated with the severity of the chronic esophagltis. These results indicate that chronic esophagltis may be involved in the natural history of esophageal carclnogenesis. Nutrient defic 相似文献
The primary goal of this study was to identify secondary functional changes in the peripheral motor units of the paretic upper extremity (UE) in patients with severe ischemic stroke and to determine how these changes develop during the first weeks after stroke. An inception cohort of 27 consecutive patients with an acute ischemic supratentorial stroke and an initial UE paralysis was compared with 10 healthy control subjects. The ulnar nerve was electrically stimulated proximal to the wrist and electromyographic recordings were obtained from the abductor digiti minimi muscle. Hemiparetic side mean values of the compound muscle action potential (CMAP) 1 and 3 weeks after stroke were compared with the nonparetic side and with CMAP values obtained from healthy control subjects. The mean CMAP amplitude in patients was significantly lower on the paretic side compared with the nonparetic side and with control subjects. Decrease in CMAP amplitude was observed in more than half of the stroke patients, sometimes as early as 4 days after stroke, and persisted in most cases. Whenever present, it was accompanied by absence of motor recovery at that specific time after stroke. Decreased CMAP amplitude in the abductor digiti minimi muscle can be seen already in the very acute phases after stroke unrelated to peripheral neuropathy, radiculopathy, or plexopathy, and it is accompanied by absence of UMN recovery. This knowledge is important for interpreting electrophysiological data in stroke patients. 相似文献
Background: Inhibition of intestinal peristalsis is a major side effect of drugs used for anesthesia or for analgesia and sedation of patients in the intensive care unit. This in vitro study examined the effect of clonidine and dexmedetomidine on intestinal peristalsis and analyzed some of their mechanisms of action.
Methods: In isolated segments of the guinea pig small intestine, peristalsis was triggered by a perfusion-induced rise of the intraluminal pressure. The peristaltic pressure threshold to elicit a peristaltic wave was used to quantify drug effects on peristalsis. Vehicle (Tyrode's solution), clonidine (10 nm-100 [mu]m), or dexmedetomidine (0.1-100 nm) were added extraserosally to the organ bath. In other series of experiments, clonidine or dexmedetomidine was administered after pretreatment with yohimbine, prazosin, apamin, naloxone, or vehicle. Clonidine was also tested after blockade of NO synthase with l-NAME and in the presence of the inactive enantiomer d-NAME.
Results: Clonidine and dexmedetomidine concentration-dependently increased peristaltic pressure threshold and inhibited peristalsis (clonidine: EC50 = 19.6 [mu]m; dexmedetomidine: EC50 = 12.0 nm). The inhibition caused by clonidine could be prevented by pretreatment with yohimbine, naloxone, and apamin, but not by prazosin, l-NAME, or d-NAME. Inhibition caused by dexmedetomidine was prevented by yohimbine only. 相似文献