丙氨瑞林对子宫内膜异位症患者骨密度的影响

目的 :探讨丙氨瑞林治疗的子宫内膜异位症患者的骨密度变化情况。方法 :选取 46例子宫内膜异位症患者作为治疗组 ,给予丙氨瑞林 15 0 μg ,sc ,疗程为 3mo。 2 8例月经周期正常的健康妇女及 18例轻度子宫膜异位症的妇女作为对照组。 结果 :治疗组与对照组骨密度均在正常范围。结论 :丙氨瑞林使用 3mo对骨密度无明显影响     

丙氨瑞林缓释微球注射剂对大鼠异位子宫内膜抑制作用

目的：观察丙氨瑞林缓释微球注射剂（LHRH-Ams）对异位内膜的抑制作用。方法：用外科自体移植术建立大鼠子宫内膜异位症动物模型,随机分组给药,同时在给药后不同时间采集血样,测定血清E₂水平。结果：LHRH-Ams作用相似于LHRH-Alp,剂量为100 μg.kg^-1.d^-1时,对大鼠异位内膜明显抑制,可达“药物性去卵巢”作用,增加剂量,作用并未相应增加。给药后1周,血清E2可降低至间情期水平,6周后开始恢复。结论：LHRH-Ams对大鼠异位子宫内膜有明显的抑制,可达“药物性去卵巢”作用,为临床应用提供实验依据。     

醋酸亮丙瑞林治疗子宫内膜异位症的临床价值

目的探讨醋酸亮丙瑞林治疗子宫内膜异位症的临床价值。方法选择我院100例2014年4月至2018年2月子宫内膜异位症术后患者。随机分组,对照组采取炔雌醇环丙孕酮片治疗,观察组则采取醋酸亮丙瑞林治疗。比较两组疾病疗效;月经复潮时间;治疗前后患者血清激素指标E_2、LH和FSH等;不良反应。结果观察组疾病疗效、月经复潮时间、血清激素指标E_2、LH和FSH等相比较对照组更好,P <0.05。观察组和对照组不良反应相似,P> 0.05。结论醋酸亮丙瑞林治疗子宫内膜异位症效果好。     

腹腔镜联合醋酸亮丙瑞林治疗子宫内膜异位症的临床观察

目的探讨腹腔镜联合醋酸亮丙瑞林治疗子宫内膜异位症的临床价值。方法选择经腹腔镜手术诊断并治疗的子宫内膜异位症患者68例,术后随机分为2组,腹腔镜术后用药组(35例)为实验组:术后第一次月经来潮第一天皮下注射醋酸亮丙瑞林3.75μg,间隔28 d注射一次,连用3~6个月;未用药组(33例)为对照组。所有患者随访12个月,观察疗效。结果术后联合用醋酸亮丙瑞林组与未用药组有效率分别为88.6%、42.4%;复发率分别为5.7%、30.3%;妊娠率分别为57.1%、21.2%。术后用药药组与未用药组比较差异具有统计学意义(P<0.05),两组均无肝脏损害。结论腹腔镜联合醋酸亮丙瑞林治疗子宫内膜异位症疗效确切,能降低复发率,提高妊娠率。     

注射用缓释醋酸亮丙瑞林治疗子宫内膜异位症临床研究

目的 对注射用缓释醋酸亮丙瑞林治疗子宫内膜异位症的临床治疗效果进行观察和分析.方法 选择45例于2012年1月~2013年10月间在本院进行子宫内膜异位症治疗的患者资料进行研究和分析,将患者分为对照组和治疗组两组,对照组20例,治疗组25例,对照组患者进行抑那通注射治疗,治疗组患者进行缓释醋酸亮丙瑞林注射治疗,对两组患者的治疗效果进行比较和分析.结果 对照组7例患者治疗显效,9例患者治疗有效,4例患者治疗无效,治疗总有效率为80%,治疗组9例显效,10例患者有效,6例无效,治疗总有效率为76%;对照组2例患者阴道出血,1例患者多汗,2例患者潮热,不良反应发生率为25%,治疗组1例阴道出血,2例多汗,1例潮热,不良反应发生率为16%,两组患者临床治疗效果、不良反应发生率差异均不具有统计学意义（P＞0.05）.结论 对注射用缓释醋酸亮丙瑞林治疗子宫内膜异位症能够取得理想的临床治疗效果.     

醋酸亮丙瑞林治疗子宫内膜异位症临床研究

目的 探讨醋酸亮丙瑞林治疗子宫内膜异位症临床效果;方法 收集我院妇科2015年1月~2016年1月收治的180例子宫内膜异位症的患者,随机分为观察组和对照组,每组90例,对照组给予米菲司酮片治疗,观察组给予醋酸亮丙瑞林治疗,观察两组治疗效果;结果 经治疗后,观察组与对照组的总有效率分别为91.11%(82/90)、78.89%(71/90),两组间比较差异显著(P<0.05);结论 醋酸亮丙瑞林治疗子宫内膜异位症临床效果显著,可提高女性的生活质量,用药简单,作用持久且安全,可尽快改善患者的临床症状.     

醋酸亮丙瑞林对子宫内膜异位症患者性激素水平及子宫体积的影响

目的:探究醋酸亮丙瑞林对子宫内膜异位症(EMS)患者性激素水平及子宫体积的影响.方法:选择2018年6月～2019年6月某院收治的90例EMS患者作为研究对象,采用随机数字表法分为观察组和对照组各45例,观察组采用炔雌醇环丙孕酮片联合醋酸亮丙瑞林治疗,对照组采用炔雌醇环丙孕酮片治疗,28d为1个疗程,两组均治疗6个疗程...     

水飞蓟素联用亮丙瑞林对子宫内膜异位症的疗效和安全性

目的考察水飞蓟素联用亮丙瑞林剂量减半法对于治疗子宫内膜异位症的疗效和安全性。方法 105位子宫内膜异位症患者随机分为两组,一组单用亮丙瑞林,另一组水飞蓟素联用亮丙瑞林,在治疗12,24个月后检测相关指标。结果与单用亮丙瑞林相比,联用组经12,24个月治疗,盆骨的慢性疼痛强度和频率减少相当,肝肾功能改善显著(P<0.05)。结论水飞蓟素能有效改善因长期服用亮丙瑞林引起的肝肾功能降低现象,水飞蓟素联用亮丙瑞林剂量减半法对于子宫内膜异位症的治疗具有积极意义。     

醋酸亮丙瑞林联合莉芙敏治疗子宫内膜异位症的临床研究

目的研究醋酸亮丙瑞林联合莉芙敏治疗子宫内膜异位症（EM）的疗效和安全性。方法选择2009年12月1日～2010年12月1日于阜新市第二人民医院妇科住院接受治疗的子宫内膜异位症患者60例,随机分为A、B组,每组各30例。A组患者术后月经复潮第1～2天内皮下注射醋酸亮丙瑞林3.75mg,每4周1次,连续6次,疗程24周;B组在使用醋酸亮丙瑞林的基础上配合口服莉芙敏,比较两组患者治疗前、后的血清激素、绝经症状严重程度、骨代谢生化指标及临床疗效。结果 （1）治疗后FSH、LH和E2水平均低于治疗前,差异有统计学意义;治疗后,B组的雌二醇水平高于A组,FSH及LH水平低于A组,但差异均无统计学意义（P〉0.05）。（2）A、B两组患者治疗后的Kupperman评分总平均分别为（19±5）分和（12±2）分,两组间比较,差异有统计学意义（P〈0.05）;两组间潮热出汗、失眠及肌肉关节疼痛的发生率比较,差异均有统计学意义（P〈0.05）;感觉异常的发生率两组间比较,差异均无统计学意义（P〉0.05）。（3）用药后均存在骨代谢生化指标钙、磷明显升高,与用药前差异有统计学意义;用药后B组患者各指标升高程度低于A组,差异有统计学意义;两组患者用药前后腰椎骨密度有显著差异,A组用药后与B组用药后相比也存在差异,B组用药前后无显著差异。（4）两组患者完全缓解率及部分缓解率无差异,复发率为A组略高于B组,推测可能与样本量小有关,有待于扩大样本进一步研究。结论皮下注射醋酸亮丙瑞林对于EM保守性手术后的巩固治疗疗效确切,同时配合口服莉芙敏是能减轻其不良反应,增强患者依从性,同时也是安全有效的。     

醋酸丙氨瑞林对人子宫内膜癌裸鼠皮下移植瘤生长的影响

目的探讨不同剂量醋酸丙氨瑞林(alarelin acetate)对人子宫内膜癌裸鼠皮下移植瘤生长的影响及作用机制。方法建立裸鼠移植瘤模型,将荷瘤裸鼠随机分为4组:实验对照组,醋酸丙氨瑞林低、中、高剂量组(0、20、40、80μg/kg)。治疗期间定期测量肿瘤大小,观察裸鼠全身状况。治疗4周后,将移植瘤完整取出,称取瘤质量,计算抑瘤率。利用免疫组织化学法检测移植瘤组织中livin蛋白的表达。结果醋酸丙氨瑞林低、中、高剂量组的抑瘤率分别为17.8%、26.5%和43.6%,与对照组比较,醋酸丙氨瑞林各治疗组肿瘤生长缓慢,差异有统计学意义(P<0.05)。免疫组织化学结果:与对照组相比,醋酸丙氨瑞林各治疗组livin蛋白的表达水平明显降低,且各治疗组间差异有统计学意义(P<0.05)。结论不同剂量的醋酸丙氨瑞林均能抑制人子宫内膜癌裸鼠移植瘤的生长,且呈剂量依赖关系,其作用机制可能与下调livin蛋白表达有关。     

丙氨瑞林对大鼠,兔异位内膜的抑制作用

采用异位内膜模型大鼠和兔，以那法瑞林、达那唑、双侧卵巢切除（ＯＶＸ）作为阳性对照，观察了丙氨瑞林（１）对异位内膜的抑制作用。结果表明皮下或肌肉注射１１０～１００μｇ／ｋｇ有明显抑制作用，且具一定的剂量相关性。该作用较达那唑强，可达ＯＶＸ水平。但较那法瑞林为弱。这一作用是１的药物性去势作用的结果。     

丙氨瑞林对下丘脑-垂体-性腺轴作用的研究

采用多种实验动物观察表明ＬＨＲＨ类似物丙氨瑞林（１）对下丘脑－垂体－性腺轴具有正向和异向作用，二者与给药剂量、持续时间有关。低剂量１单次或短期给药可诱发兔排卵、大鼠血清促性腺激素ＬＨ水平升高、成年雌猴血清雌二醇水平增高、幼小白鼠子宫重量增加。后者与１长期给药使雌性大鼠子宫组织萎缩的作用恰好相反。１长期给药也使大鼠单侧卵巢切除诱发的对侧卵巢代偿性肥大反应受抑。成年雌猴连续给药１１个月，诱导血清雌二醇和孕酮升高的反应均较首次注射时的诱导作用为低。     

Effect of chronic treatment with nafarelin on estradiol receptor content within eutopic and ectopic endometrium in rabbits

本实验旨在研究那法瑞林（Ｎａｆ）对兔正位和异位子宫内膜组织内雌激素受体（ＥＲ）含量的影响．以手术方法制备兔异位内膜模型后,将兔分为对照组,Ｎａｆ１,３,１０μｇ·ｋｇ－１·ｄ－１,ｓｃ治疗组以及手术切除双侧卵巢（ＯＶｘ）组．６周后发现,经Ｎａｆ和ＯＶｘ治疗的兔,其子宫的重量及其内膜组织内的ＥＲ数量明显减少．但对异位子宫内膜组织内ＥＲ的免疫组织化学分析结果表明,Ｎａｆ长期应用并未引起异位内膜ＥＲ数量的明显改变．结果提示Ｎａｆ对兔子宫的抑制作用可能通过ＥＲ介导,而其对异位子宫内膜的抑制作用则可能与ＥＲ无关．     

去氧孕烯炔雌醇联合维生素B6治疗原发性痛经疗效观察

目的观察去氧孕烯炔雌醇联合维生素B6治疗原发性痛经的临床效果。方法将62例原发性痛经患者随机分为观察组和对照组各31例。观察组采用去氧孕烯炔雌醇联合维生素B6治疗;对照组仅予维生素B6治疗。治疗后比较2组临床疗效。结果观察组总有效率为93.5%高于对照组的74.2%,差异有统计学意义(P<0.05)。结论去氧孕烯炔雌醇联合维生素B6治疗原发性痛经安全有效。     

Amodiaquine, its desethylated metabolite, or both, inhibit the metabolism of debrisoquine (CYP2D6) and losartan (CYP2C9) in vivo

Objective To study the extent of in vivo inhibition by the antimalarial drug amodiaquine, its active metabolite N-desethylamodiaquine, or both, of the metabolism of four probe drugs of the enzymes CYP2D6, CYP2C19, CYP2C9 and CYP1A2.Methods Twelve healthy Swedish volunteers received a cocktail of four probe drugs (debrisoquine, omeprazole, losartan and caffeine) to determine their baseline metabolic capacities. After a washout period, they received a 600 mg oral dose of amodiaquine hydrochloride; and 2–3 h later the cocktail was administered again. One week after the intake of amodiaquine, the subjects received the cocktail a third time. The levels of probe drugs and their metabolites as well as amodiaquine and its metabolite were determined by HPLC.Results Plasma levels of amodiaquine and N-desethylamodiaquine could be followed in all subjects for 6 h and 28 days, respectively. Among the 12 subjects, a 3-fold variation in amodiaquine AUC and a 2-fold variation in N-desethylamodiaquine AUC, were observed. The CYP2D6 and CYP2C9 activities of the subjects were measured by debrisoquine and losartan phenotyping tests, respectively. There were significant mean increases in debrisoquine metabolic ratio (MR) between baseline and the second cocktail [MR_{2 h}−MR_baseline 1.426 (95% confidence interval 1.159, 1.755), P=0.002; ANOVA, Fisher LSD test] and in mean losartan MR between baseline and the second cocktail [MR_{2 h}−MR_baseline 1.724 (95% confidence interval 1.076, 2.762), P=0.026; ANOVA, Fisher LSD test]. The effects on CYP2D6 and CYP2C9 activities subsided within a week after intake of amodiaquine as tested by the phenotyping cocktail. The changes in omeprazole MRs and caffeine MRs were not statistically significant between any of the study phases.Conclusion A single dose of amodiaquine decreased CYP2D6 and CYP2C9 activities significantly compared to baseline values. Amodiaquine has the potential to cause drug-drug interactions and should be further investigated in malarial patients treated with drug combinations containing amodiaquine.     

2-(3, 6, 7-三甲氧基菲-9-基-甲基)-2, 5-二氢吡咯的合成

目的 制备具有多种生物活性的菲并吲哚里西定类生物碱的关键中间体2-(3, 6, 7-三甲氧基菲-9-基-甲基)-2, 5-二氢吡咯。方法 以2, 2, 2-三氯-N-[1-(3, 6, 7-三甲氧基菲-9-基甲基)-丁-2-烯基]乙酰胺为起始原料,经水解、Boc保护、N-烯丙基化、关环复分解反应及脱保护基等5步反应得到目标化合物。结果与结论 合成了2- (3, 6, 7-三甲氧基菲-9-基甲基)-2, 5-二氢吡咯,其结构经¹H-NMR谱确证总收率为45.3%。     

Modulation of constitutive androstane receptor (CAR) and pregnane X receptor (PXR) by 6-arylpyrrolo[2,1-d][1,5]benzothiazepine derivatives, ligands of peripheral benzodiazepine receptor (PBR)

Constitutive androstane receptor (CAR) and pregnane X receptor (PXR) regulate xenobiotic sensing and metabolism through interactions with multiple exogenous and endogenous chemicals. Compounds that activate CAR are often ligands of PXR; attention is therefore given to discovery of new, receptor-specific chemical entities that may be exploited for therapeutic and basic research purposes. Recently, ligands of the peripheral benzodiazepine receptor (PBR), PK11195 and FGIN-1-27, were shown to modulate both CAR and PXR. PBR is a mitochondrial transport protein responsible for multiple regulatory functions, including heme biosynthesis, a major component in cytochrome P450 (CYP) enzymes. To investigate possible new roles for PBR involvement in metabolic regulation, expression of the CAR and PXR target genes, CYP2B6 and CYP3A4, was measured in human hepatocytes following treatment with a targeted PBR ligand set. Luciferase reporter assays with transiently expressed wild-type CAR (CAR1), splice variant CAR3, or PXR in HuH-7 cells were used to further study activation of these receptors. Four structurally related PBR ligands (benzothiazepines) differentially modulate CAR1, CAR3 and PXR activity. Benzothiazepine NF49 is an agonist ligand of CAR3, a partial agonist of PXR, exhibits greater inverse agonist activity on CAR1 than does PK11195, and is a new tool for studying these closely related nuclear receptors.     

紫草羟基萘醌对大鼠肝微粒体CYP2D6的影响

目的研究紫草羟基萘醌（HNA）对大鼠肝微粒体CYP2D6的影响。方法 Wistar大鼠,♂,口服给予不同剂量的HNA（5,60 mg.kg-1.d-1）或等量的空白溶媒,连续给药2周后制备肝微粒体。以体外探针药物右美沙芬的代谢物右啡烷的生成速率来反映CYP2D6的活性,通过比较给药组与空白溶媒组酶活性的差异来评价HNA对大鼠肝微粒体CYP2D6的影响。结果建立了一种以右美沙芬为探针底物评价大鼠肝微粒体CYP2D6活性的方法。口服给予HNA两周后,两个剂量组大鼠的肝微粒体蛋白含量、细胞色素P450总量、b5含量以及CYP2D6的活性与空白溶媒组相比差异均无统计学意义。结论 5 mg.kg-1.d-1和60 mg.kg-1.d-1剂量的紫草羟基萘醌口服2周对Wistar大鼠肝微粒体CYP2D6的活性均无显著影响,没有明显的诱导或抑制作用。     

维拉帕米对HeLa细胞12C6+离子辐射敏感性的影响

利用重离子加速器国家重点实验室提供的12C6+束流照射人宫颈瘤(HeLa)细胞,测量辐射结束后细胞克隆率绘制细胞存活曲线。使用10μg/mL的维拉帕米处理细胞作为一组对照,检测维拉帕米对于HeLa细胞辐射敏感性的影响。利用Fluo-3 AM钙离子荧光探针配合流式细胞仪检测重离子照射后的胞内游离钙(IECa2+)水平。实验结果表明0～5 Gy范围内重离子辐射剂量与HeLa细胞存活率负相关,照射结束后胞质游离钙浓度有一定程度的上升。而维拉帕米能显著降低HeLa细胞经重离子辐射后的存活及增殖能力,且胞质游离钙浓度处于较低水平。造成这种现象的原因可能是维拉帕米能降低细胞对非致死性DNA损伤的修复能力。     

Effects of bis(6-mercaptopurine-9-beta-D-ribofuranoside)-5',5"-phosphate and its butyryl derivative on mouse leukaemia L1210 and a 6-mercaptopurine-resistant subline in culture

Bis(6-mercaptppurine-9-β-d-ribofuranoside)-5′-5″′-monophosphate (bis(MPR)P) and its butyryl derivative, bis(O²,$\text{O}{}^3\text{-}\text{dibutyryl}\text{-6-}\text{mercaptopurine}\text{-9-β-}\text{d}\text{-}\text{ribofuranoside}$)-5′,5″′-monophosphate (bis(dibutyrylMPR)P) were synthesized from 6-mercaptopurine-9-β-d-ribofuranoside (MPR). Bis(MPR)P (ec₅₀ = 0.014 μM) and MPR (ec₅₀ = 0.022 μM) were essentially equivalent in their growth inhibitory activities against L1210/0 cell cultures, whilst bis(dibutyrylMPR)P (ec₅₀ = 1.1 μM) was considerably less effective. L1210/MPR cells grew normally in the presence of 1 mM MPR but were inhibited by bis(MPR)P (ec₅₀ = 580 μM) and (bis(dibutyrylMPR)P (ec₅₀ = 42 μM). Bis(dibutyrylMPR)P was less readily broken down to MPR by enzymes in the serum component of the culture medium than was bis(MPR)P, and leukaemia cells did not contribute to the extracellular degradation of the acylated derivative. The delayed cytotoxic effects of bis(MPR)P and bis(dibutyrylMPR)P on L1210/0 cells were those of the MPR breakdown product. Exposure to bis(MPR)P resulted in delayed cytotoxicity in L1210/MPR cultures whilst bis(dibutyrylMPR)P produced only acute growth inhibition and no delayed effect on the MPR-resistant subline. MPR was incorporated into DNA of L1210/0 cells as 6-thioguanine deoxyribonucleotide whilst bis(MPR)P was not incorporated into L1210/MPR cell DNA. These results suggested that the ultimate mechanisms of action of bis(MPR)P and bis(dibutyrylMPR)P in L1210/ MPR cells may have been different from that of MPR in sensitive L1210/0 cells and therefore might not represent true circumvention of resistance to MPR.