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11.
抗孕激素RU486和ZK98734对双池培养的颗粒细胞和内泡膜细胞分泌功能的影响 总被引:1,自引:0,他引:1
本文观察了RU486和ZK98734对培养在羊膜双池培养系统中的猪卵巢颗粒细胞和内泡膜细胞在甾体激素生成过程中的影响。生长在羊膜两书侧的颗粒细胞和内泡膜细胞在加入或不加FSH、LH及不同浓度RU486或ZK98734的条件下培养48h。用RIA测定内、外池培养液中的孕酮(P)和雌二醇(E2)的浓度并与单独培养的结果相比较,同时亦与大鼠颗粒细胞的结果作比较。结果表明:1.有FSH刺激时,两种抗孕激素均明显抑制双池培养中颗粒细胞的P和E2产量;2.不论有或无LH刺激,两种抗孕激素均显著抑制双池培养中内泡膜细胞的P产量;3.双池培养系统模拟了两种卵巢细胞在体内的旁分泌调节关系,比单独培养更加合理;4与大鼠相比,猪卵巢细胞体外培养是研究避孕药对卵巢功能影响的适合模型。 相似文献
12.
米非司酮对子宫肌层异位内膜组织细胞凋亡的影响 总被引:2,自引:0,他引:2
目的 :通过观察米非司酮对子宫肌层异位内膜组织细胞凋亡的影响 ,探讨子宫腺肌病的发病机制。方法 :确诊后的 5 0例患者 ,分成两组 ,实验组 2 5例 ,用药前行卵功、肝肾功能检查 ,结果回报正常后 ,给予口服 RU4 86 2 5 mg/ d,每日一次 ,连服 2 w。另外 2 5例为对照组。 5 0例患者均选择在月经增生期 ,月经后 3~ 7d,实验组开始服药 ,停药后立即手术 ;对照组住院后立即手术 ,手术切除子宫 ,取少许子宫异位内膜组织蜡块包埋待检。切除的子宫全部送病理。将 5 0块包埋的蜡块经处理后 ,采用原位末端酶标记技术检测细胞凋亡数 ,计算出凋亡指数 ,免疫组化法检测抗凋亡基因 Bcl- 2及促凋亡基因 Fas的表达水平。结果 :服米非司酮的实验组细胞凋亡指数平均为 11%± 9% ,而对照组细胞凋亡指数平均为 0± 0 .4 % ,两组比较有显著差异 ,P<0 .0 1。RU4 86可以下调 Bcl- 2基因 ,使其在子宫腺肌病患者子宫肌层的内膜中表达减低 ,Fas基因表达增强。结论 :米非司酮使子宫肌层异位内膜组织细胞凋亡指数增加 ,Bcl- 2表达降低 ,Fas表达增强。从而证实 ,米非司酮可诱导异位内膜组织细胞凋亡 ,抑制异位细胞生长 ,控制子宫腺肌病的发展 ,为保守治疗子宫腺肌病提供一条新的可靠的途径 相似文献
13.
《Journal of labelled compounds & radiopharmaceuticals》2005,48(9):657-668
We demonstrated the synthesis of carbon‐11 labeled 17‐α‐hydroxy‐11‐β‐/4‐/[methyl]‐[1‐methylethyl]‐aminophenyl/‐17α‐[prop‐1‐ynyl]esta‐4‐9‐diene‐3‐one (RU40555), a selective glucocorticoid receptor (GR) antagonist, and examined the in vivo profile of [11C]RU40555. [11C]RU40555 was synthesized by direct N‐methylation with [11C]CH3OTf at 60°C for 5 min and an injectable solution of [11C]RU40555 was obtained in 31 min at the end of bombardment. The decay‐corrected radiochemical yield was 19%, the specific radioactivity was 57.5±14.0 GBq/µmol, and the radiochemical purity was more than 99% as determined by HPLC. In rat experiments, the effects of adrenalectomy (ADX) on brain accumulation of [11C]RU40555 were examined. ADX significantly decreased plasma corticosterone levels, and significantly increased brain accumulation of [11C]RU40555. We succeeded in developing a rapid automated synthesis method for [11C]RU40555, a GR antagonist, and showed [11C]RU40555 had a potential as a PET tracer for mapping GR. Copyright © 2005 John Wiley & Sons, Ltd. 相似文献
14.
Central mineralocorticoid receptors are indispensable for corticosterone-induced impairment of memory retrieval in rats 总被引:1,自引:0,他引:1
Previous studies indicated that stress levels of glucocorticoid hormones (cortisol in humans, and corticosterone in rodents) induce impairment of long-term memory retrieval, but the underlying mechanisms (genomic or nongenomic) are not clear. To clarify this issue, we investigated the involvement of brain corticosteroid receptors and protein synthesis in the corticosterone-induced impairment of memory retrieval. Young rats were trained in the water maze task with six trials per day for 6 consecutive days. Retention of the spatial training was assessed 24 h after the last training session with a 60-s probe trial. Experiments included intraventricular injections of anisomycin, a specific protein synthesis inhibitor or specific antagonists for both types of corticocosteroid receptors (mineralocorticoid receptor, MR, and glucocorticoids receptor, GR) before corticosterone administration shortly before retention testing. The results showed that administration of anisomycin did not change the corticosterone response. Administration of the MR, but not GR, antagonist blocked the corticosterone-induced response dose dependently. These findings provide evidence for the view that glucocorticoids impair memory retrieval through nongenomic mechanisms involving an interaction with central MRs. 相似文献
15.
High throughput ranking of recombinant avian scFv antibody fragments from crude lysates using the Biacore A100 总被引:1,自引:0,他引:1
Leonard P Säfsten P Hearty S McDonnell B Finlay W O'Kennedy R 《Journal of immunological methods》2007,323(2):172-179
Advances in molecular evolution strategies have made it possible to identify antibodies with exquisite specificities and also to fine-tune their biophysical properties for practically any specified application. Depending on the desired function, antibody/antigen interactions can be long-lived or short-lived and, therefore, particular attention is needed when seeking to identify antibodies with specific reaction-rate and affinity properties. Surface plasmon resonance (SPR) biosensors routinely generate sensitive and reliable kinetic data from antibody/antigen interactions for both therapeutic and diagnostic applications. However, many kinetic-based screening assays require rigorous sample preparation and purification prior to analysis. To ameliorate this problem, we developed a rapid and reliable assay for characterising recombinant scFv antibody fragments, directly from crude bacterial lysates. Ninety-six scFv antibodies derived from chickens immunised with C-reactive protein (CRP) were selected by phage display and evaluated using the Biacore A100 protein interaction array system. Antibodies were captured from crude bacterial extracts on the sensor chip surface and ranked based on the percentage of the complex left (% left) after dissociation in buffer. Kinetic rate constants (k(a) and k(d)) and affinity (K(D)) data were obtained for six clones that bound monomeric CRP across a broad affinity range (2.54 x 10(-8) to 3.53 x 10(-10) M). Using this assay format the A100 biosensor yielded high quality kinetic data, permitting the screening of nearly 400 antibody clones per day. 相似文献
16.
BACKGROUND: Diabetes is associated with an excess risk of cardiac events, and one risk factor for infarction is an elevated level of plasminogen activator inhibitor-1 (PAI-1). OBJECTIVES AND METHODS: To evaluate whether the glucocorticoid hormones are involved in the diabetes-induced PAI-1 production, we examined expression profiles of PAI-1 mRNA in adrenalectomized (ADX) mice with streptozotocin (STZ)-induced diabetes. RESULTS: The diabetes-induced augmentation of plasma PAI-1 levels and PAI-1 mRNA expression in the heart and lungs was completely normalized in diabetic ADX mice. The glucocorticoid receptor antagonist RU486 significantly, but only partly suppressed PAI-1 induction in STZ-induced diabetic mice, suggesting that factors other than glucocorticoids are also involved in PAI-1 induction provoked by diabetes. CONCLUSION: Our results suggested that the adrenal gland plays a critical role in the progression of thrombosis in diabetic patients by inducing expression of the PAI-1 gene. 相似文献
17.
Päivi Kankkunen Elina Välimäki Johanna Rintahaka Jaana Palomäki Tuula Nyman Harri Alenius Henrik Wolff Sampsa Matikainen 《Human immunology》2014
Inflammasome is an intracellular molecular platform of the innate immunity that is a key mediator of inflammation. The inflammasome complex detects pathogens and different danger signals, and triggers cysteine protease caspase-1-dependent processing of pro-inflammatory cytokines IL-1β, and IL-18 in dendritic cells and macrophages. Previously, we have shown that water-damaged building associated trichothecene mycotoxins, including roridin A, trigger IL-1β and IL-18 secretion in human macrophages. However, the molecular basis as well as mechanism behind this trichothecene-induced cytokine secretion has remained uncharacterized. Here, we show that the trichothecene-induced IL-1β secretion is dependent on NLRP3 inflammasome in human primary macrophages. Pharmacological inhibition and small interfering RNA approach showed that the trichothecene-induced NLRP3 inflammasome activation is mediated through ATP-gated P2X7 receptor. Moreover, we show that trichothecene-triggered NLRP3 inflammasome activation is dependent on Src tyrosine kinase activity. In addition, gene silencing of c-Cbl, a negative autophagy-related regulator of c-Src, resulted in enhanced secretion of IL-1β and IL-18 in response to trichothecene mycotoxin stimulation in human macrophages. In conclusion, our results suggest that roridin A, a fungal trichothecene mycotoxin, acts as microbial danger signals that trigger activation of NLRP3 inflammasome through P2X7R and Src tyrosine kinase signaling dependent pathway in human primary macrophages. 相似文献
18.
米非司酮和PG联用终止早孕的宫内超声图象及临床处理 总被引:5,自引:0,他引:5
本文通过对68例年龄22~35岁,停经84~54天,应用米非司酮和PG终止妊娠的妇女,因用药后未见妊娠囊排出或因出血较多而作的子宫B超检查,概括并描述了药流后继续妊娠、妊娠囊及蜕膜组织官腔内滞留的超声图象,并提出了相应的处理原则。我们认为,在米非司酮和PG联合终止早孕的临床中应用B超监护,对减少并发症具有重要意义。 相似文献
19.
国产半合成米非司酮临床药代动力学 总被引:6,自引:1,他引:6
24例早孕妇女分别口服不同剂量的国产半合成米非司酮(RU486),以HPLC测定其血清母药及其代谢产物(RU42633,RU42848和RU42698)浓度,并以免疫火箭电泳测定α-酸糖蛋白(AAG)血清水平。结果显示米非司酮吸收和代谢均很迅速,口服20min后可测得母药.2h以后RU42633水平开始超过母药水平。母药峰浓度(CMAX)与剂量不成比例。按二室开放模型和非空模型计算,母药消除半衰期均随剂量而变化。但在600mg组,CMAX与0、24和48h的AAG平均水平呈显著正相关(r=0.9299,P<0.01),结果提示米非司酮在人体内代谢里非线性过程,AAG在一定程度上影响该化合物血清浓度与代谢过程。 相似文献
20.
孕妇及非孕妇口服不同剂量RU 486后的药物动力学研究 总被引:7,自引:3,他引:7
非孕妇(n=9)及早孕妇(n=36)口服不同剂量RU 486后,以HPLC测定服药后RU486及其代谢产物RU 42633、RU 42848和RU 42698的血浆浓度,结果显示不论妊娠与否,药物的吸收及代谢都很迅速;服药后20 min 即可测得血浆中的RU 486及其代谢产物;母药达峰时间Tmax 均为1~2h,其峰浓度Cmax 对数与剂量对数之间呈显著正相关。服相同剂量后,非孕组药-时曲线水平及药时曲线下面积AUC 大于早孕组,但两组间并无显著性差异(P>0.05)。无论非孕组及早孕组,口服25 mg、100 mg 和200 mg后,RU 486代谢符合二室开放模型,口服400 mg 和600mg 后则呈非线性动力学过程。 相似文献