定坤丹联合炔诺酮治疗月经不调的临床研究

目的探讨定坤丹联合炔诺酮治疗月经不调的临床疗效。方法选取2017年3月—2019年3月在开封市人民医院治疗的月经不调患者92例,根据用药的差别分为对照组(46例)和治疗组(46例)。对照组口服炔诺酮片,2.5mg/次,4次/d;治疗组在对照组基础上口服定坤丹,7 g/次,2次/d。两组患者均经过3个月经周期治疗。观察两组患者临床疗效,同时比较治疗前后两组患者临床症候积分、性激素水平、月经失血图(PBAC)、中华生存质量量表(Ch QOL)、高温相评分(HPS)、匹茨堡睡眠质量指数量表(PSQI)评分以及血清细胞因子水平。结果治疗后,对照组临床有效率为82.61%,显著低于治疗组的97.83%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者症候积分明显下降(P0.05),且治疗组临床症候积分明显低于对照组(P0.05)。治疗后,两组血清孕酮(P)、雌二醇(E2)水平显著升高(P0.05),黄体生成激素(LH)、促卵泡成熟激素(FSH)水平显著下降(P0.05),且治疗组E2、P、LH和FSH水平明显好于对照组(P0.05)。治疗后,两组PBAC和PSQI评分显著下降(P0.05),Ch QOL和HPS评分显著升高(P0.05),且治疗组PBAC、PSQI、Ch QOL和HPS评分明显好于对照组(P0.05)。治疗后,两组患者血清表皮生长因子(EGF)、血管内皮生长因子(VEGF)水平均明显升高(P0.05),且治疗组EGF和VEGF水平明显高于对照组(P0.05)。结论定坤丹联合炔诺酮片治疗月经不调可有效改善患者临床症状,改善机体性激素水平,提高患者睡眠和生活质量。     

The correlation of serum protein association and cellular uptake with lipophilicity and polarity of the backbone substituents of the technetium‐99m‐amine‐oxime chelates

Detection of tumor hypoxia is of importance because hypoxic cancer cells can resist radiation therapy and also induce molecules to help them surviving and metastasizing. Our previous study has reported the development of technetium‐99m labeled amine‐oxime compounds containing 2‐nitroimidazoles to target hypoxic cells. In order to develop new generation of ^99mTc, ⁶⁴Cu, and ⁶⁷Cu based amine‐oxime chelates with improved selectivity on tumor hypoxia in the future, it is important to understand the correlation of some structural parameters such as lipophilicity and polarity of the backbone ‐constituents of a radiochelate with its serum protein binding potential and cellular‐uptake‐level. The correlation is investigated in this work by using five ^99mTc‐amine‐oxime chelates containing 2‐NI group and another five containing aniline group (as control). The results indicate that the level of protein‐and cellular‐binding of a radiochelate increased with their lipophilicity which generally correlates with the lengthening of the alkyl chains on the backbone of the radiochelates. The greater lipophilicity of a radiochelate, the higher percentage it bound to serum proteins and cellular membrane. Our study also indicates that, in addition to lipophilicity, polarity of the constituents is also an important factor of determining the levels of serum protein binding and cellular accumulation of a radiochelate. Copyright © 2007 John Wiley & Sons, Ltd.     

三苯氧胺或炔诺酮合用前列腺素抗早孕效果观察

本文比较三苯氧胺(TMX)或炔诺酮(NET)配伍dl-15-甲基前列晾素F_(2α)(15-m-PGF_(2α))的抗早孕效果。共123例早孕妇女,分成四组,Ⅰ组:单纯用TMX;Ⅱ组:TMX合用15-m-PGF_(2α)海绵栓;Ⅲ组TMX合用15-m-PGF_(2α)注射剂;Ⅵ纽NET合用15-m-PGF_(2α)注射剂。抗早孕效果以Ⅳ组最佳,完全流产率达95%(与其它三组比较P<0.05),不全流产率3.3%,其余依次Ⅲ组完全流产率85%,不全流产率15%;Ⅱ组完全流产率50%,不全流产率30%;Ⅰ组完全流产率8.7%。NET与15-m-PGF_(2α)配伍的抗早孕效果优于TMX,且价格便宜,建议临床可推广使用。     

复方庚炔诺酮对小鼠骨髓细胞及胎肝血微核率的影响

本文用微核试验测定了复方庚炔诺酮对小鼠骨髓细胞及胎肝血微核率的影响。复方庚炔诺酮1,5,10及100mg/kg组小鼠骨髓多染性红细胞的微核率分别为2.4,2,2.2及2.8‰;复方庚炔诺酮10,50及100mg/kg组胎肝血微核率分别为2.7,3.3及4‰。溶剂对照组小鼠骨髓多染性红细胞及胎肝血微核率为1.8～3‰,复方庚炔诺酮与对照组之间微核率并无显著差异(P>0.06)。阳性对照药物环磷酰胺组微核率为49～64.3‰。结果提示复方庚炔诺酮似不具有明显的遗传毒性效应。     

Norethisterone is bioconverted to oestrogenic compounds that activate both the oestrogen receptor alpha and oestrogen receptor beta in vitro

In the present study, we used [3H]norethisterone to explore the bioconversion of this compound to A-ring reduced metabolites in African Green Monkey Kidney CV-1 cells and breast cancer T-47D cells. Additionally, we analyzed the capability of each norethisterone tetrahydro-reduced compound to bind the human oestrogen receptors alpha and beta and transactivate an oestrogen-sensitive reporter gene. The results showed that norethisterone is mainly metabolized to 3 alpha,5 alpha-norethisterone (>85% of total [3H]norethisterone added) by CV-1 and T-47D cells, and that both A-ring tetrahydro-reduced metabolites exhibit different capabilities to displace [3H]17beta-oestradiol from the oestrogen receptor alpha and beta, being 3 alpha,5 alpha-norethisterone the weakest competitor. We also found that 3 alpha,5 alpha-norethisterone and 3beta,5 alpha-norethisterone activate both oestrogen receptors at nanomolar concentrations and that the transactivation induced by the oestrogen receptor alpha was generally higher (1.7- to 4.0-fold) than that provoked by the beta receptor isoform. In oestrogen receptor alpha-transfected CV-1 and T-47 D cells, the oestrogenic-like potency of the 3beta,5 alpha-tetrahydro-reduced form was similar to that exhibited by 17beta-oestradiol and 2.5- to 4.0-fold higher than that shown by the 3 alpha,5 alpha-reduced compound; conversely, in the oestrogen receptor beta system the potency of the natural ligand was higher than that presented by the 3beta,5 alpha-tetrahydro-reduced metabolite. In CV-1 cells expressing the oestrogen receptor beta, the transactivation potency of 3beta,5 alpha-norethisterone was approximately 2-fold higher than that exhibited by its 3 alpha,5 alpha-tetrahydro-reduced isomer, whereas in T-47D cells the potency of the 3 alpha,5 alpha-tetrahydro-reduced compound was slightly higher than that shown by the 3beta,5 alpha A-ring reduced norethisterone metabolite. These results demonstrate that CV-1 and T-47D cells possess the enzymatic machinery to bioconvert norethisterone into the 5 alpha-reduced, 3 alpha-hydroxylated form and that neither 3 alpha,5 alpha- or 3beta,5 alpha-norethisterone exhibit preference or selectivity towards a particular oestrogen receptor isoform to induce a particular oestrogenic effect in these cell lines.     

咪唑肟醚类衍生物的合成及其抗真菌活性

按文献报道采用立体选择性合成方法,合成了新抗真菌药物——Oxiconazole(奥昔康唑,4a),并对其合成中间体N-(2,4-二氯苯甲酰甲基)咪唑(2)的制备方法进行了改进。为通过结构改造获得抗真菌活性更强的化合物,我们合成了7个咪唑肟醚类衍生物(4b-g,7),其中6个系首次报道。合成产物经元素分析证明结构。体外抑菌试验表明化合物4a-g和7对多数菌株的抗菌活性强于克霉唑,且化合物4c具有抗曲霉菌活性,而Oxiconazole等其它眯唑肟醚类化合物则无此作用。化合物4a的结构经UV、IR、~1H-NMR、MS确证,并首次提供了其粉末X射线衍射图及数据。此化合物已用于临床试验,其对股癣的2周治愈率达94.10％,明显高于益康唑(84.24％,P<0.01)。     

Synthesis and biological activity of conformationally controlled 2-PAM derivatives

A series of conformationally controlled 2-PAM derivatives were prepared from 2-acetylpyridine and 2,3-pyrido[b]cycloalkenones in two steps and their reactivities towards parathion poisoned AChE were evaluated. The most planar 2,3-pyrido[b]cyclohexanone oxime methiodide showed an activity comparable to 2-PAM implying E-syn is that the most active conformation of 2-PAM in the biological system.     

Assessment of changes in regional cerebral blood flow in patients with major depression using the 99mTc-HMPAO single photon emission tomography method

Regional cerebral blood flow was investigated in 14 patients with major depression diagnosed according to the DSM-III-R criteria (six patients with single and eight patients with recurrent episodes) and in ten healthy volunteers. The mean ages of the patients and the controls were 33.5 ± 2.7 and 31.6 ± 2.6 years, respectively. The severity of the depression was assessed using the 17-item Hamilton Depression Scale (mean: 23.2 ± 1.5). None of the patients was under medication. After administration of 500 MBq technetium-99m hexamethylpropylene amine oxime, a single photon emission tomography study was performed and then transaxial, sagittal and coronal slices were obtained. For the semiquantitative analysis of the data, the ratios of the mean counts/pixel to the whole slice were calculated for 24 regions on three consecutive transaxial slices in the orbitomeatal plane. Additionally, left/right and frontal/occipital ratios were calculated. Both sides of the temporal region had a significantly decreased cerebral blood flow (CBF) when compared to the controls. The left/right ratio of the prefrontal region was also significantly lower in the patients than in the controls. The Hamilton score had a negative correlation with blood flow in the anterofrontal and left prefrontal regions. According to our results, regional CBF seems to be decreased in the left prefrontal and in both temporal regions in major depression. The severity of depression is correlated with the reduction in CBF in the regions of the anterofrontal and left prefrontal cortex.