Synthesis and evaluation of 6-[(18)F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine as a PET tracer for nicotinic acetylcholine receptors

Both ABT-594 ((R)-2-chloro-5-(2-azetidinylmethoxy)pyridine) and A-85380 (3-[2(S)-2-azetidinylmethoxy]pyridine), novel nicotinic agonists that possess potent non-opioid analgesic properties, have high affinity for neuronal nicotinic acetylcholine receptors (nAChR) but do not elicit the pronounced toxicity of epibatidine. 6-[(18)F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (6-[(18)F]fluoro-A-85380), a F-18 labeled analogue of these two compounds, is therefore a promising radioligand for positron emission tomography (PET) studies in humans. The use of trimethylammonium as a leaving group in nucleophilic aromatic substitution reactions has proven to be a versatile and efficient strategy, and offers several advantages over other leaving groups. Here, we report the synthetic strategy for the preparation of a precursor, as a trimethylammonium iodide salt, and its use in the radiosynthesis to 6-[(18)F]fluoro-A-85380. Preliminary compartative PET studies of 6-[(18)F]fluoro-A-85380 and 2-[(18)F]fluoro-A-85380 were carried out in baboon to examine their suitability as tracers for studying nAChR system.     

Increased chromatid-type chromosomal aberrations in mouse m5S cells exposed to power-line frequency magnetic fields

PURPOSE: To investigate the induction of chromosomal aberrations in mouse m5S cells after exposure to power-line frequency magnetic fields (extremely low frequency magnetic fields; ELFMF) at high-flux densities. MATERIAL AND METHOD: m5S cells were either untreated or pretreated during the G1 phase with mitomycin C (MMC, 1 microM) for 1 h or 3 Gy X-rays, and then exposed to ELFMF at three different flux densities (5 and 50 mT at 60 Hz, 400 mT at 50 Hz) for 40 h. Unexposed control cells were incubated for the same period in a conventional CO2 incubator. Chromosomal aberrations were analysed in the first post-treatment metaphases. Cell kinetics were assessed by DNA flow cytometry and the mitotic index. RESULTS AND CONCLUSIONS: ELFMF enhanced the formation of spontaneous and MMC- or X-ray-induced chromosomal aberrations, in a flux-density-dependent manner. Statistically significant increases in the frequency of chromosomal aberrations were observed in cells exposed to 400 mT ELFMF with respect to unexposed controls. The aberrations induced by ELFMF were mostly chromatid-type, not chromosome-type. The cells exposed to 400 mT ELFMF exhibited a three-fold higher level of chromatid-type aberrations than did the unexposed cells. Flow cytometric and mitotic index analyses revealed that the S or G2 arrest following MMC or X-irradiation was more profound in ELFMF-exposed cells than in unexposed cells. Our results suggest that ELFMF can interfere with post-replication repair, resulting in increased levels of chromatid-type chromosomal aberrations induced spontaneously and by DNA damaging agents.     

固相化细胞吸附浓集法分离污水中脊髓灰质炎病毒的实验研究

〔目的〕建立一个适用于污水中脊髓灰质炎病毒分离培养的方法。〔方法〕采用固相化的L2 0B细胞吸附法 ,浓集污水中的脊髓灰质炎病毒 ,将浓集物再用活的L2 0B细胞培养。〔结果〕能够检出 10 0 0ml水中的 0 .1～ 10TCID50 量的脊髓灰质炎病毒 ,在10 0 0ml预处理后的污水中加入 10TCID50 量的病毒 ,亦可以检出。〔结论〕本方法的有效检出限为 10TCID50 / 10 0 0ml,可用于污水中的脊髓灰质炎病毒的浓集和分离培养。     

被忽视的宝贝

小测试 Q1：你去菜场买肉的时候,是不是从不要肉皮？ Q2：清洗鱼的时候,你是不是将鱼鳞和鱼的内脏一起扔掉？ Q3：吃鱼的时候,你是不是也很随意地丢掉了鱼眼睛？ Q4：你是不是只吃过辣椒,而从没尝试过辣椒叶的味道？     

Causal influences in primate cerebral cortex during visual pattern discrimination

Anatomical studies of the visual cortex demonstrate the existence of feedforward, feedback and lateral pathways among multiple cortical areas. Yet relatively little evidence has previously been available to show the causal influences of these areas on one another during visual information processing. We simultaneously recorded event-related local field potentials (LFPs) from surface-to-depth bipolar electrodes at six sites in the ventral region of the right hemisphere visual cortex in a highly trained macaque monkey during performance of a visual pattern discrimination task. Applying a new statistical measure, the short-time directed transfer function (STDTF), to the LFP data set, we charted the changing strength and direction of causal influence between these cortical sites on a fraction-of-a-second time scale. We present results showing, for the first time, the dynamics of distinct feedforward, feedback and lateral influences in the ventral portion of the primate visual cortex during visual pattern processing.     

左氧氟沙星注射液致过敏性休克1例分析

患者女,42岁,于2005年4月10日,因尿频、尿急、尿痛2d就诊,查体T 37℃,BP16/9 Kpa,心率68·min-1,心肺未见异常,双下肢无水肿,双侧肾区无叩击痛,既往健康,无药物过敏史,未曾应用过左氧氟沙星。查血常规:WBC10×109L-1、N78%。尿常规,BLD()、GLU()、Pro(+)、WBC()。镜检,WBC 10×15个/HP。临床诊断为,急性泌尿系感染。医嘱给予抗生素治疗。静脉滴注0·9%生理盐水250ml+左氧氟沙星0·3g 30min后,患者感胸闷、伴有大汗、脉搏细弱。询问患者晨起后未进早餐,考虑为低血糖反应。医嘱减慢滴速,多饮水,20min后症状缓解。第二天重复上述药物…     

Expression of cytochrome p450 and other biotransformation genes in fetal and adult human nasal mucosa.

Despite recent progress in the identification and characterization of numerous nasal biotransformation enzymes in laboratory animals, the expression of biotransformation genes in human nasal mucosa remains difficult to study. Given the potential role of nasal biotransformation enzymes in the metabolism of airborne chemicals, including fragrance compounds and therapeutic agents, as well as the potential interspecies differences between laboratory animals and humans, it would be highly desirable to identify those biotransformation genes that are expressed in human nasal mucosa. In this study, a global gene expression analysis was performed to compare biotransformation enzymes expressed in human fetal and adult nasal mucosa to those expressed in liver. The identities of a list of biotransformation genes with apparently nasal mucosa-selective expression were subsequently confirmed by RNA-polymerase chain reaction (PCR) and DNA sequencing of the PCR products. Further quantitative RNA-PCR experiments indicated that, in the fetus, aldehyde dehydrogenase 6 (ALDH6), CYP1B1, CYP2F1, CYP4B1, and UDP glucuronosyltransferase 2A1 are expressed preferentially in the nasal mucosa and that ALDH7, flavin-containing monooxygenase 1, and glutathione S-transferase P1 are at least as abundant in the nasal mucosa as in the liver. The nasal mucosal expression of CYP2E1 was also detected. These findings provide a basis for further explorations of the metabolic capacity of the human nasal mucosa for xenobiotic compounds.     

中医医院急诊工作的建议

中医医院急诊工作不仅关系着中医医院综合服务功能的完善,而且也是医院可持续发展的标志之一.笔者认为,中医医院急诊工作必须注重以下几个方面.     

随机森林和决策树模型在轻型缺血性脑卒中患者复发预测中的应用分析

目的 构建轻型缺血性脑卒中（MIS）患者2年内复发的随机森林和决策树预测模型,并分析模型的临床应用价值。方法 回顾性收集2020年7月1日至12月31日于山西省心血管病医院神经内科就诊的520例MIS患者的病历资料,根据2年内是否复发将患者分为复发组和未复发组。基于缺失森林对数据进行填补,根据文献检索与专家讨论结果筛选预测变量并进行单因素分析,合成少数过采样技术-标称连续（SMOTE-NC）技术处理数据不平衡,采用贝叶斯优化十折交叉验证构建随机森林、决策树模型并与Logistic回归模型进行比较。基于受试者工作特征曲线下面积（AUC）、布里尔分数（BS）与校准曲线分别评价模型的区分度与校准度。对预测性能最好的模型采用SHAP模型解释预测结果。结果 2年内复发患者共93例（17.9%）。两组患者的年龄,吸烟、糖尿病、循环梗死部位、多发性脑梗死比例,以及舒张压、红细胞压积、血小板计数、低密度脂蛋白水平比较,差异有统计学意义（P<0.05）。Logistic回归模型、决策树模型与随机森林模型在测试集中,预测MIS患者2年内复发情况的AUC(95%CI)分别为0.764(0.691～0....