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Morphine-6-Glucuronide Isomers-Synthesis and Biological Evaluation
Jixia Yang,Guanyi Lu,Gongzheng Zhang,Xiaodi Wang,Hongliang Wen,Cipan Huang,Jiazhen Yin,Jin Li 대한화학회 2020 Bulletin of the Korean Chemical Society Vol.41 No.11
Morphine-6?-D-glucuronide (M6?G), an active metabolite of morphine, and its isomer morphine-6α-D-glucuronide (M6αG) were synthesized from 3-O-protected morphinethrough glycosylation and alkaline hydrolysis. All structures were determined by spectroscopic analysis, and especially it is the first time to report the single crystal of compound M6αG. In vitro binding assay showed that M6?G bound to mu opioid receptor (MOR), kappa opioid receptor (KOR), and delta opioid receptor (DOR) with nanomolar affinity (Ki = 28.03, 116.88, and 375.13?nM) and M6αG bound to them with similar affinity (Ki = 1070.13, 20?637.93, and 677.36?nM). The selectivity of M6αG toward KOR is much higher. Hot-plate test showed that the analgesic effect of M6?G is better than that of M6αG, that is maybe because the mechanism of M6αG is different.
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Yang Xu,Lu Xia,Liu Jun,Kan Ying,Wang Wei,Zhang Shuxin,Liu Lei,Li Jixia,Yang Jigang 대한영상의학회 2022 Korean Journal of Radiology Vol.23 No.4
Objective: 18F-fluorodeoxyglucose (FDG) PET/CT is often used for detecting malignancy in patients with newly diagnosed hemophagocytic lymphohistiocytosis (HLH), with acceptable sensitivity but relatively low specificity. The aim of this study was to improve the diagnostic ability of 18F-FDG PET/CT in identifying malignancy in patients with HLH by combining 18F-FDG PET/CT and clinical parameters. Materials and Methods: Ninety-seven patients (age ≥ 14 years) with secondary HLH were retrospectively reviewed and divided into the derivation (n = 71) and validation (n = 26) cohorts according to admission time. In the derivation cohort, 22 patients had malignancy-associated HLH (M-HLH) and 49 patients had non-malignancy-associated HLH (NM-HLH). Data on pretreatment 18F-FDG PET/CT and laboratory results were collected. The variables were analyzed using the Mann-Whitney U test or Pearson’s chi-square test, and a nomogram for predicting M-HLH was constructed using multivariable binary logistic regression. The predictors were also ranked using decision-tree analysis. The nomogram and decision tree were validated in the validation cohort (10 patients with M-HLH and 16 patients with NM-HLH). Results: The ratio of the maximal standardized uptake value (SUVmax) of the lymph nodes to that of the mediastinum, the ratio of the SUVmax of bone lesions or bone marrow to that of the mediastinum, and age were selected for constructing the model. The nomogram showed good performance in predicting M-HLH in the validation cohort, with an area under the receiver operating characteristic curve of 0.875 (95% confidence interval, 0.686–0.971). At an appropriate cutoff value, the sensitivity and specificity for identifying M-HLH were 90% (9/10) and 68.8% (11/16), respectively. The decision tree integrating the same variables showed 70% (7/10) sensitivity and 93.8% (15/16) specificity for identifying M-HLH. In comparison, visual analysis of 18F-FDG PET/CT images demonstrated 100% (10/10) sensitivity and 12.5% (2/16) specificity. Conclusion: 18F-FDG PET/CT may be a practical technique for identifying M-HLH. The model constructed using 18F-FDG PET/CT features and age was able to detect malignancy with better accuracy than visual analysis of 18F-FDG PET/CT images.
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