BACKGROUND & AIMS: AIM:To evaluate the tissular expression of Androgen (A), Estrogen (E) and Progesterone (Pg) receptors, and Apolipoprotein D (ApoD), in liver tumors from resected hepatocellular carcinoma (HCC) cases in order to assess their possible relationship to prognosis. METHODS:We performed an immunohistochemical study using tissue microarrays (containing more than 260 cancer specimens, from 31 HCC patients and controls) to determine the presence of specific antibodies against AR, ER, PgR and ApoD, correlating their findings with several clinico-pathological and biological variables. The staining results were categorized using a semi-quantitative score based on their intensity, and the percentage of immunostained cells was measured. RESULTS:A total of 21 liver tumors (67.7%) were positive for AR; 16 (51.6%) for ER; 26 (83.9%) for PgR and 12 (38.7%) stained for ApoD. We have found a wide variability in the immunostaining score values for each protein, with a median (range) of 11.5 (11.5-229.5) for AR; 11.1 (8.5-65) for ER; 14.2 (4-61) for PgR; and 37.7 (13.8-81.1) for ApoD. A history of heavy ethanol consumption, correlated positively with AR and PgR and negatively with ER status. HCV chronic infection also correlated positively with AR and PgR status. However, the presence of ApoD immunostaining did not correlate with any of these variables. Tumors with a positive immuno-staining for PgR showed a better prognosis. CONCLUSION:Our results indicate a moderate clinical value of the steroid receptor status in HCC, emphasizing the need to perform further studies in order to evaluate the possible role of new hormonal-based therapies.

背景与目标：

BACKGROUND & AIMS: :Male pigs are routinely castrated at a young age to prevent the formation of androstenone, a 16-androstene testicular steroid that is a major component of boar taint. The practice of castration has been increasingly viewed as unfavorable, due to both economic considerations and animal welfare concerns. Other means of controlling boar taint, including reducing the synthesis of androstenone in the testes, would eliminate the need for castration. In this study, we determined the effects of transactivation of three nuclear receptors, the constitutive androstane receptor (CAR), pregnane X receptor (PXR), and farnesoid X receptor (FXR), on gene expression and steroid hormone metabolism in primary porcine Leydig cells. Primary cells were isolated from mature boars, and transcript expression levels were assayed using real-time PCR. The transcripts of interest included porcine orthologs of common phase I and phase II metabolic enzymes, enzymes involved in steroidogenesis, and transcripts previously shown to be differentially expressed in boars with high androstenone and boar taint levels. Transactivation of CAR, PXR, or FXR increased the expression of several genes involved in steroidogenesis, including cytochrome B5A (CYB5A) and cytochrome B5 reductase 1 (CYB5R1), as well as hydroxysteroid (17-beta) dehydrogenase 4 (HSD17B4) and retinol dehydrogenase 12 (RDH12). Treatment with (6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl)oxime (CITCO), a CAR agonist, or rifampicin (RIF), a PXR agonist, resulted in significantly (p<0.05) decreased sex steroid production and significantly (p<0.05) increased production of 16-androstene steroids. Treatment with the FXR agonist chenodeoxycholic acid (CDCA) resulted in significantly (p<0.05) decreased sex steroid production. These results indicate that transactivation of these nuclear receptors may lead to increased levels of 16-androstene steroids, likely by altering the activity of CYP17A1 through CYB5A and CYB5R1 to the andien-β synthase reaction and away from the 17α-hydroxylase and C17, 20 lyase reactions.

背景与目标： : 公猪通常在幼年时就被阉割，以防止雄烯酮的形成，雄烯酮是一种16-雄烯酮睾丸类固醇，是公猪污染的主要成分。由于经济考虑和动物福利方面的考虑，阉割的做法越来越被认为是不利的。其他控制公猪污染的方法，包括减少睾丸中雄烯酮的合成，将消除去势的需要。在这项研究中，我们确定了组成型雄激素受体 (CAR)，孕烷X受体 (PXR) 和法尼醇X受体 (FXR) 三种核受体的反式激活对原发性猪Leydig细胞的基因表达和类固醇激素代谢的影响。从成熟公猪中分离原代细胞，并使用实时PCR测定转录本表达水平。感兴趣的转录本包括常见的I期和II期代谢酶的猪直系同源物，与类固醇生成有关的酶以及先前显示在雄烯酮和公猪污染水平高的公猪中差异表达的转录本。CAR，PXR或FXR的反式激活增加了与类固醇生成有关的几个基因的表达，包括细胞色素B5A (CYB5A) 和细胞色素B5还原酶1 (CYB5R1) 以及羟基类固醇 (17-beta) 脱氢酶4 (HSD17B4) 和视黄醇脱氢酶12 (RDH12)。用 (6-(4-氯苯基) 咪唑并 [2,1-b][1,3) thiazole-5-carbaldehyde-O-(3,4-二氯苄基) 肟 (CITCO) (一种CAR激动剂) 或利福平 (RIF) (一种PXR激动剂) 治疗，导致性类固醇生成显著 (p<0.05) 减少，16-雄激素类固醇生成显著 (p<0.05) 增加。用FXR激动剂鹅去氧胆酸 (CDCA) 治疗导致性类固醇生成显著 (p<0.05) 减少。这些结果表明这些核受体的反式激活可能导致16-雄激素类固醇水平升高，可能通过将CYP17A1的活性通过CYB5A和CYB5R1改变为andien-β 合酶反应，并远离17α-羟化酶和C17，20裂解酶反应。

BACKGROUND & AIMS: Human endometrium undergoes sequential changes during the menstrual cycle and becomes receptive to implantation during a defined period in the secretory phase. We attempted to identify the genes expressed during this period by representational difference analysis (RDA). When the cDNAs of a proliferative endometrium were used as the driver and the cDNAs of a post-ovulatory day 5 endometrium were used as the tester, a number of bands were identified by RDA. DNA of the cloned RDA products revealed that the majority of the clones contained a fragment of a cDNA identical to that of a crystallin B chain. Northern blot analysis showed that the expression of the alpha crystallin B chain mRNA was absent during the proliferative phase. The expression of the mRNA of alpha crystallin B chain first appeared in the secretory phase, progressively increased during this phase and peaked in the late secretory endometria. The pattern of expression of alpha crystallin B chain mRNA in the endometrium of mature cycling baboons (Papio anubis) was similar to that seen in human endometrium. As revealed by Western blot analysis, the expression of the alpha crystallin B chain protein in human endometrium followed a pattern of expression similar to its mRNA. At the cellular level, the immunoreactive protein first appeared in the surface epithelial cells of human endometrium within the implantation window without significant immunoreactivity in the underlying glandular cells. During the mid- and late secretory phases, the intensity of staining in the epithelial cells was enhanced and an intense immunoreactivity was developed in the glandular epithelium, alpha crystallin B chain was virtually an epithelial product and no immunoreactivity for this protein was detectable in the stromal cells, endothelial cells or lymphoid cells. The expression of alpha crystallin B chain could be regulated, by medroxy progesterone acetate as well as by oestrogen withdrawal, in human endometrial carcinoma cells (EnCa-101), transplanted to nude mice. Based on the data presented here, the known function of alpha crystallin B chain and its distinct pattern of expression in human endometrium, we suggest that this protein is an important factor within the molecular repertoire that makes endometrium receptive to implantation.

背景与目标： 人子宫内膜在月经周期中经历顺序变化，并在分泌期的特定时期接受植入。我们试图通过代表性差异分析 (RDA) 来鉴定在此期间表达的基因。当将增生性子宫内膜的cdna用作驱动程序，并将排卵后第5天子宫内膜的cdna用作测试仪时，RDA鉴定出许多条带。克隆的RDA产物的DNA显示，大多数克隆包含与晶体蛋白B链相同的cDNA片段。Northern印迹分析表明，在增殖期不存在 α 晶体蛋白B链mRNA的表达。Α 晶体蛋白B链mRNA的表达首先出现在分泌期，在此期逐渐增加，并在分泌期晚期子宫内膜达到峰值。成熟循环狒狒 (Papio anubis) 子宫内膜中 α 晶体蛋白B链mRNA的表达模式与人子宫内膜中相似。如Western印迹分析所示，人子宫内膜中 α 晶体蛋白B链蛋白的表达遵循与其mRNA相似的表达模式。在细胞水平上，免疫反应蛋白首先出现在植入窗口内的人子宫内膜表面上皮细胞中，而在下层腺体细胞中没有显着的免疫反应性。在分泌期中期和晚期，上皮细胞的染色强度增强，腺上皮细胞产生了强烈的免疫反应性，α 晶体蛋白B链实际上是上皮产物，在基质细胞，内皮细胞或淋巴样细胞中没有检测到该蛋白的免疫反应性。在移植到裸鼠的人子宫内膜癌细胞 (EnCa-101) 中，醋酸甲羟孕酮和雌激素戒断可以调节 α 晶体蛋白B链的表达。根据此处提供的数据，已知的 α 晶体蛋白B链的功能及其在人子宫内膜中的独特表达模式，我们建议该蛋白是使子宫内膜易于植入的分子库中的重要因素。

BACKGROUND & AIMS: :Acute graft-versus-host disease (aGvHD) reduces the efficiency and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In recent years, attempts have been made to transplant fecal microbiota from healthy donors to treat intestinal GvHD. This study presented two cases of patients undergoing allo-HSCT who were later selected for fecal microbiota transplantation (FMT). In the first patient, FMT resulted in the complete resolution of symptoms, whereas therapeutic efficacy was not achieved in the second patient. FMT eliminated drug-resistant pathogens, namely very drug-resistant Enterococcus spp., but not multidrug-resistant Acinetobacter baumannii or Candida spp. Further research is needed, particularly on the safety of FMT in patients with intestinal steroid-resistant GvHD and on the distant impact of transplanted microflora on the outcomes of allo-HSCT. FMT appears promising for the treatment of patients with steroid-resistant GvHD.

背景与目标： 急性移植物抗宿主病 (aGvHD) 降低异基因造血干细胞移植 (allo-HSCT) 的效率和安全性。近年来，人们尝试移植来自健康供体的粪便微生物群来治疗肠道GvHD。这项研究介绍了两例接受allo-HSCT的患者，这些患者后来被选为粪便微生物群移植 (FMT)。在第一例患者中，FMT导致症状完全缓解，而在第二例患者中未达到治疗效果。FMT消除了耐药病原体，即非常耐药的肠球菌属，但没有多药耐药的鲍曼不动杆菌或念珠菌属。需要进一步的研究，尤其是关于FMT在肠道类固醇耐药GvHD患者中的安全性以及移植菌群对allo-HSCT结局的远距离影响。FMT对于类固醇耐药GvHD患者的治疗似乎很有希望。

BACKGROUND & AIMS: :Neurosteroids are powerful modulators of brain function and behavior, yet their dynamics in the brain have remained elusive. Using in vivo microdialysis in male zebra finches, we found that local estradiol levels increased rapidly in the forebrain during social interactions with females. Furthermore, when males were exposed to other males' songs, local estradiol levels also increased and testosterone levels dropped in a cortical/pallial auditory region that is analogous to mammalian auditory cortex. We also found that local estradiol and testosterone levels were differentially regulated in this same region by the conventional neurotransmitters glutamate and GABA, respectively. This study provides direct evidence that forebrain steroid levels are acutely and differentially regulated during social behavior in a region-specific manner and in a rapid time course similar to that of traditional neuromodulators.

背景与目标： : 神经类固醇是大脑功能和行为的强大调节剂，但它们在大脑中的动态仍然难以捉摸。在雄性斑马雀中使用体内微透析，我们发现在与雌性的社交互动中，前脑中的局部雌二醇水平迅速增加。此外，当男性暴露于其他男性的歌曲时，类似于哺乳动物听觉皮层的皮质/苍白质听觉区域的局部雌二醇水平也会升高，睾丸激素水平也会下降。我们还发现，在同一区域，常规神经递质谷氨酸和GABA分别对局部雌二醇和睾丸激素水平进行了差异调节。这项研究提供了直接证据，表明前脑类固醇水平在社交行为中以特定区域的方式和与传统神经调节剂相似的快速时间过程受到急性和差异调节。

BACKGROUND & AIMS: :The outcomes of the treatment of thrombotic thrombocytopenic purpura (TTP) have been shown to be improved by the administration of plasma exchange. However, treatment options are currently limited for cases refractory to plasma exchange. The autoantibodies that block the activity of ADAMTS13 have been demonstrated to play a role in the pathogenesis of TTP; therefore, high-dose immunoglobulin, which can neutralize these autoantibodies, may be useful for refractory TTP. However, successful treatment with high-dose immunoglobulin for TTP refractory to plasma exchange and corticosteroids has yet to be reported in Korea. Herein, we describe a refractory case which was treated successfully with high-dose immunoglobulin. A 29-year-old male diagnosed with TTP failed to improve after plasma exchange coupled with additional high-dose corticosteroid therapy. As a salvage treatment, we initiated a 7-day regimen of high-dose immunoglobulin (400 mg/kg) infusions, which resulted in a complete remission, lasting up to the last follow-up at 18 months. High-dose immunoglobulin may prove to be a useful treatment for patients refractory to plasma exchange; it may also facilitate recovery and reduce the need for plasma exchange.

背景与目标： : 血栓性血小板减少性紫癜 (TTP) 的治疗结果已通过血浆置换得到改善。但是，对于难治性血浆置换的病例，目前的治疗选择有限。已证明阻断ADAMTS13活性的自身抗体在TTP的发病机理中起作用; 因此，可以中和这些自身抗体的大剂量免疫球蛋白可能对难治性TTP有用。然而，韩国尚未报道大剂量免疫球蛋白对血浆置换和皮质类固醇难治性TTP的成功治疗。在本文中，我们描述了用高剂量免疫球蛋白成功治疗的难治性病例。一名29岁的男性被诊断为TTP，在血浆置换联合其他大剂量皮质类固醇治疗后未能改善。作为挽救性治疗，我们开始了为期7天的大剂量免疫球蛋白 (400 mg/kg) 输注方案，从而完全缓解，持续到最后一次随访18个月。大剂量免疫球蛋白可能被证明是难治性血浆置换患者的有用治疗方法; 它还可以促进恢复并减少对血浆置换的需求。

BACKGROUND & AIMS: :Uptake of organic solutes and xenobiotics by mammalian cells is mediated by ATP-independent transporters, and four families of transporters have now been identified. To search for novel organic solute transporters, a liver cDNA library from an evolutionarily primitive marine vertebrate, the little skate Raja erinacea, was screened for taurocholate transport activity by using Xenopus laevis oocytes. In contrast to the organic anion transporters identified to date, a transport activity was identified in this library that required the coexpression of two distinct gene products, termed organic solute transporter alpha and beta (Ostalpha, Ostbeta). Ostalpha cDNA encodes for a protein of 352 aa and seven putative transmembrane (TM) domains. Ostbeta contains 182 aa and has at least one and perhaps two TM domains. There is no significant sequence identity between Ostalpha and Ostbeta, and only low identity with sequences in the databases; however, Ostalpha bears a resemblance to some G protein-coupled receptors, and Ostbeta exhibits 22% amino acid identity with the C-terminal TM and intracellular domains of protocadherin-gamma, a cell surface glycoprotein. Xenopus oocytes injected with the cRNA for both Ostalpha and Ostbeta, but not each separately, were able to take up taurocholate, estrone sulfate, digoxin, and prostaglandin E(2), but not p-aminohippurate or S-dinitrophenyl glutathione. Transport was sodium-independent, saturable, and inhibited by organic anions and steroids, including the major skate bile salt, scymnol sulfate. These results identify an organic anion transporter composed of a putative seven-helix TM protein and an ancillary membrane polypeptide.

背景与目标： : 哺乳动物细胞对有机溶质和异种生物的吸收是由ATP非依赖性转运蛋白介导的，现在已经确定了四个转运蛋白家族。为了寻找新的有机溶质转运蛋白，使用非洲爪蟾卵母细胞筛选了来自进化原始海洋脊椎动物小溜冰鞋Raja erinacea的肝脏cDNA文库的牛磺胆酸盐转运活性。与迄今为止鉴定的有机阴离子转运蛋白相反，在该文库中鉴定出一种转运活性，该转运活性需要两种不同基因产物的共表达，称为有机溶质转运蛋白 α 和 β (Ostalpha，Ostbeta)。Ostalpha cDNA编码352 aa和七个推定的跨膜 (TM) 结构域的蛋白质。Ostbeta包含182 aa并且具有至少一个和可能两个TM结构域。Ostalpha和Ostbeta之间没有显着的序列同一性，仅与数据库中的序列低同一性; 但是，Ostalpha与某些g蛋白偶联受体相似，Ostalpha与原钙粘蛋白-γ 的C末端TM和细胞内结构域具有22% 的氨基酸同一性，一种细胞表面糖蛋白。注射了用于Ostalpha和Ostbeta的cRNA的非洲爪蟾卵母细胞 (但不是分别) 能够吸收牛磺胆酸盐，硫酸雌酮，地高辛和前列腺素E(2)，但不能吸收对氨基马尿酸盐或S-二硝基苯基谷胱甘肽。转运是钠非依赖性的，可饱和的，并受到有机阴离子和类固醇的抑制，包括主要的冰鞋胆盐，硫酸scymnol。这些结果确定了由推定的七螺旋TM蛋白和辅助膜多肽组成的有机阴离子转运蛋白。

BACKGROUND & AIMS: :The aim of this study was to investigate the effect of oxandrolone on body composition in boys with constitutional delay of growth and puberty. In 14 prepubertal boys, height, weight, triceps and subscapular skinfolds and upper arm circumference were measured. Body mass index, the ratio of subscapular to triceps skinfolds and the upper muscle area were also determined. The difference of the various measurements and indices, 3 to 6 months before and after commencement of oxandrolone treatment, were calculated, while the boys remained prepubertal. We observed a marked increase in body mass index, a decrease of triceps and subscapular skinfolds, an increase in the ratio of subscapular to triceps skinfolds and also an increase in upper muscle area after the onset of oxandrolone treatment. These results suggest that low dose oxandrolone administration in prepubertal boys with constitutional growth delay causes a disproportionate increase of weight to height which is largely due to increased body muscle.

背景与目标： : 这项研究的目的是研究奥沙洛尔酮对发育和青春期体质延迟的男孩身体成分的影响。在14个青春期前男孩中，测量了身高，体重，三头肌和肩胛下皮褶和上臂围。还确定了体重指数，肩cap下与肱三头肌皮褶的比率以及上肌面积。计算了开始奥沙酮治疗前后3至6个月的各种测量和指标的差异，而男孩仍处于青春期前。我们观察到在开始oxandrolone治疗后，体重指数显着增加，肱三头肌和肩胛下皮褶减少，肩胛下与肱三头肌皮褶的比例增加以及上肌面积增加。这些结果表明，在具有体质生长延迟的青春期前男孩中，低剂量的oxandrolone给药会导致体重与身高不成比例的增加，这在很大程度上是由于身体肌肉的增加。

BACKGROUND & AIMS: :The aim of the present study was to describe the normal cellular distribution of progesterone receptors in the canine ovary at different stages of the oestrous cycle. Samples of both ovaries were obtained from 75 healthy adult bitches of various breeds and ages, including five pregnant bitches and three bitches that had just delivered. The presence of progesterone receptors was visualized by immunohistochemistry on paraffin wax sections using a monoclonal antibody. Nuclear staining for progesterone receptors was observed in the surface epithelium, cortical tubules, rete ovarii, follicle cells, thecal cells, luteal cells, granulosa cell cords and ovarian stroma. The staining intensity for progesterone receptors in the follicle cells increased with the stage of follicle development, indicating an intrafollicular role of progesterone in the mechanism of ovulation and luteinization. The stronger staining intensities for progesterone receptors in thecal cells compared with follicle cells may be explained by the fact that thecal cells mediate some effects of steroid hormones on the follicle cells in secondary and tertiary follicles. Little correlation was found between the expression of progesterone receptors in follicle cells and oestradiol, progesterone or testosterone concentrations. This finding indicates a different regulating mechanism for progesterone receptors in canine ovarian follicles compared with other tissues of the genital tract. During pregnancy all groups of ovarian cells had lower staining intensity scores than during the oestrous cycle, although the sex steroid hormone concentrations in pregnant bitches were similar to those in non-pregnant bitches during the luteal phase of the oestrous cycle. The lower expression of progesterone receptors during pregnancy may be due to higher tissue concentrations of progesterone that are not reflected in the serum because of haemodilution and increased metabolism and clearance during pregnancy.

背景与目标： : 本研究的目的是描述在发情周期的不同阶段，犬卵巢中孕酮受体的正常细胞分布。两个卵巢的样本都是从75个不同品种和年龄的健康成年母狗中获得的，其中包括五个怀孕的母狗和三个刚分娩的母狗。使用单克隆抗体通过石蜡切片上的免疫组织化学观察孕酮受体的存在。在表面上皮，皮质小管，卵巢，卵泡细胞，鞘细胞，黄体细胞，颗粒细胞索和卵巢基质中观察到孕激素受体的核染色。卵泡细胞中孕激素受体的染色强度随着卵泡发育阶段的增加而增加，表明孕激素在排卵和黄体化机制中的卵泡内作用。与卵泡细胞相比，卵泡细胞中孕酮受体的染色强度更强，这可以解释为卵泡细胞介导了类固醇激素对次级和三级卵泡中卵泡细胞的某些作用。卵泡细胞中孕酮受体的表达与雌二醇，孕酮或睾丸激素浓度之间几乎没有相关性。这一发现表明，与生殖道其他组织相比，犬卵巢卵泡中孕酮受体的调节机制不同。在怀孕期间，所有卵巢细胞组的染色强度评分均低于发情周期，尽管在发情周期的黄体期，怀孕母狗中的性类固醇激素浓度与未怀孕母狗中的性类固醇激素浓度相似。孕酮受体在怀孕期间的表达较低，可能是由于孕酮的组织浓度较高，而由于血液稀释和妊娠期间的新陈代谢和清除率增加而未在血清中反映出来。

BACKGROUND & AIMS: BACKGROUND:Treatment of adults with steroid-dependent minimal change nephrotic syndrome (SD-MCNS) can be a significant challenge. Cyclophosphamide (CYC) and cyclosporin (CYA) are often effective steroid-sparing agents. Tacrolimus (TAC) may be another treatment option. METHODS:This open, prospective cohort study enrolled Chinese adults with SD-MCNS. At the start of the study, we administered TAC or intravenous CYC together with prednisone (0.5 mg/kg/day), the dose of which was tapered off throughout the study. The TAC cohort received oral TAC (target trough blood level of 4-8 ng/ml) for 24 weeks and the CYC cohort received intravenous CYC (750 mg/m(2) body surface) once every 4 weeks for 24 weeks. RESULTS:Twenty-six patients met the criteria for enrollment (14 patients in the CYC group and 12 patients in the TAC group). One patient from each group discontinued treatment because of a drug-related side effect. Complete remission (CR) after the 24-week therapeutic period was 76.9% (10/13) in the CYC group and 90.9% (10/11) in the TAC group. The mean time required for CR in the TAC group was significantly less than in the CYC group (P = 0.031). Eight of 13 (61.5%) patients in the CYC group and 8 of 11 (72.7%) patients in the TAC group successfully stopped steroids and changed their status from steroid dependence. Sixty percent (6/10) of the CYC patients and 50% (5/10) of the TAC patients who achieved CR maintained remission during the follow-up period of 23.0 +/- 10.1 months. Four (40%) CYC patients and five (50%) TAC patients experienced relapses, and two CYC patients experienced frequent relapses. CONCLUSION:A 24-week course of TAC is a favorable steroid-sparing agent for treatment of Chinese adults with SD-MCNS. Therapy with TAC accompanied by a tapering dose of prednisolone appears to yield quicker remission than treatment with CYC together with prednisone.

背景与目标：

BACKGROUND & AIMS: :Enzyme labeling of steroids by the p-nitrophenyl ester method was investigated in comparison with the N-succinimidyl ester method. The active ester of a testosterone or 11-deoxycortisol derivative was treated with beta-galactosidase and horseradish peroxidase to give labeled antigens. Various molar ratios of steroid to enzyme and pH conditions were tested. Satisfactory immunoreactivities with an anti-steroid antibody in each enzyme immunoassay system were obtained with the labeled antigens prepared at pH 8.5 by the use of molar ratios higher than 30. The enzyme labeling method should be useful in the case of polar steroids or drugs, since the p-nitrophenyl ester is relatively stable when compared with the N-succinimidyl ester.

背景与目标： : 与N-琥珀酰亚胺酯法相比，研究了对硝基苯酯法对类固醇的酶标记。用 β-半乳糖苷酶和辣根过氧化物酶处理睾丸激素或11-脱氧皮质醇衍生物的活性酯，得到标记的抗原。测试了类固醇与酶的各种摩尔比以及pH条件。通过使用高于30的摩尔比，在pH 8.5下制备的标记抗原，在每个酶免疫测定系统中获得与抗类固醇抗体的令人满意的免疫反应性。酶标记方法在极性类固醇或药物的情况下应该是有用的，因为与N-琥珀酰亚胺酯相比，对硝基苯酯相对稳定。

BACKGROUND & AIMS: :The steroid sulfatase or steryl sulfatase is a microsomal enzyme widely distributed in human tissues that catalyzes the hydrolysis of sulfated 3-hydroxy steroids to the corresponding free active 3-hydroxy steroids. Since androgens and estrogens may be synthesized inside the cancerous cells starting from dehydroepiandrosterone sulfate (DHEAS) and estrone sulfate (E(1)S) available in blood circulation, the use of therapeutic agents that inhibit steroid sulfatase activity may be a rewarding approach to the treatment of androgeno-sensitive and estrogeno-sensitive diseases. In the present study, we report the chemical synthesis and biological evaluation of a new family of steroid sulfatase inhibitors. The inhibitors were designed by adding an alkyl, a phenyl, a benzyl, or a benzyl substituted at position 17alpha of estradiol (E(2)), a C18-steroid, and enzymatic assays were performed using the steroid sulfatase of homogenized JEG-3 cells or transfected in HEK-293 cells. We observed that a hydrophobic substituent induces powerful inhibition of steroid sulfatase while a hydrophilic one was weak. Although a hydrophobic group at the 17alpha-position increased the inhibitory activity, the steric factors contribute to the opposite effect. As exemplified by 17alpha-decyl-E(2) and 17alpha-dodecyl-E(2), a long flexible side chain prevents adequate fitting into the enzyme catalytic site, thus decreasing capacity to inhibit the steroid sulfatase activity. In the alkyl series, the best compromise between hydrophobicity and steric hindrance was obtained with the octyl group (IC(50) = 440 nM), but judicious branching of side chain could improve this further. Benzyl substituted derivatives of estradiol were better inhibitors than alkyl analogues. Among the series of 17alpha-(benzyl substituted)-E(2) derivatives studied, the 3'-bromobenzyl, 4'-tert-butylbenzyl, 4'-butylbenzyl, and 4'-benzyloxybenzyl groups provided the most potent inhibition of steroid sulfatase transformation of E(1)S into E(1) (IC(50) = 24, 28, 25, and 22 nM, respectively). As an example, the tert-butylbenzyl group increases the ability of the E(2) nucleus to inhibit the steroid sulfatase by 3000-fold, and it also inhibits similarly the steroid sulfatase transformations of both natural substrates, E(1)S and DHEAS. Interestingly, the newly reported family of steroid sulfatase inhibitors acts by a reversible mechanism of action that is different from the irreversible mechanism of the known inhibitor estrone sulfamate (EMATE).

背景与目标： 类固醇硫酸酯酶或甾基硫酸酯酶是一种广泛分布在人体组织中的微粒体酶，可催化硫酸化的3-羟基类固醇水解为相应的游离活性3-羟基类固醇。由于雄激素和雌激素可以从血液循环中可用的硫酸脱氢表雄酮 (DHEAS) 和硫酸雌酮 (E(1)S) 开始在癌细胞内部合成，使用抑制类固醇硫酸酯酶活性的治疗剂可能是治疗雄激素敏感和雌激素敏感疾病的有益方法。在本研究中，我们报告了一个新的类固醇硫酸酯酶抑制剂家族的化学合成和生物学评估。通过添加在雌二醇 (E(2)) 的17α 位被取代的烷基、苯基、苄基或苄基来设计抑制剂，C18-steroid，并且使用均质化JEG-3细胞或在HEK-293细胞中转染的类固醇硫酸酯酶进行酶促测定。我们观察到疏水取代基会强烈抑制类固醇硫酸酯酶，而亲水取代基则较弱。尽管17α 位的疏水基团增加了抑制活性，但空间因子却产生了相反的作用。如17α-癸基-e (2) 和17α-十二烷基-e (2) 所示，长的柔性侧链阻止了对酶催化位点的充分拟合，从而降低了抑制类固醇硫酸酯酶活性的能力。在烷基系列中，辛基基团 (IC(50) = 440 nM) 获得了疏水性和空间位阻之间的最佳折衷，但是侧链的明智支化可以进一步改善这一点。雌二醇的苄基取代衍生物比烷基类似物更好。在研究的17种 α-(苄基取代)-E(2) 衍生物系列中，3 '-溴苄基，4'-叔丁基苄基，4 '-丁基苄基，和4'-苄氧基苄基对类固醇硫酸酯酶将E(1)S转化为E(1) 提供最有效的抑制作用 (IC(50) 分别为24、28、25和22 nM)。例如，叔丁基苄基将E(2) 核抑制类固醇硫酸酯酶的能力提高了3000倍，并且它也类似地抑制了天然底物E(1) 和DHEAS的类固醇硫酸酯酶转化。有趣的是，新报道的类固醇硫酸酯酶抑制剂家族通过可逆的作用机制起作用，该作用机制不同于已知抑制剂氨基磺酸盐雌酮 (EMATE) 的不可逆机制。

BACKGROUND & AIMS: :This study investigated in vitro endocrine disrupting effects of three mixtures of POPs: 'Marine mix' extracted from Atlantic cod liver, and two mixtures extracted from burbot liver, 'Mjøsa mix' and 'Losna mix'. The POP mixtures were chemically characterized. Co-culture of theca and granulosa cells, were exposed for 48h with different doses of 'Marine mix', 'Mjøsa mix' or 'Losna mix'. As an end point cell viability was determinated by LDH test, steroid analysis by EIA and caspase-3 by colorimetric substrate. Chemical characterization of the mixtures demonstrated that the 'Marine mix' contained high levels of DDTs and PCBs. In the 'Mjøsa mix', the dominant pollutants were BDEs and HBCD. The concentrations of POPs measured in the 'Losna mix' were considerably lower. All mixtures used in the present study had a stimulatory effect on testosterone and estradiol secretion with 'Marine mix'>'Mjøsa mix'>'Losna mix'. These results show that even a mixture containing background concentrations of POPs significantly affected steroid secretion. A higher steroidogenic response in low dose ranges, compared with high dose ranges indicated xenobiotic-conditioning hormesis. This could complicate predictions of effects in risk assessments.

背景与目标： : 这项研究调查了三种持久性有机污染物混合物的体外内分泌干扰作用: 从大西洋鳕鱼肝中提取的 “海洋混合物”，以及从burbot肝脏中提取的两种混合物 “mj ø samix” 和 “losna mix”。POP混合物经过化学表征。用不同剂量的 “海洋混合物”，“mj ø samix” 或 “losna混合物” 暴露卵泡膜和颗粒细胞的共培养48小时。作为终点，通过LDH测试，通过EIA进行类固醇分析并通过比色底物caspase-3测定细胞活力。混合物的化学特征表明，“海洋混合物” 中含有高水平的滴滴涕和多氯联苯。在 “mj ø samix” 中，主要污染物是溴二苯醚和六溴环十二烷。在 “losna混合物” 中测得的POPs浓度要低得多。本研究中使用的所有混合物均通过 “海洋混合物”> “mj ø samix”> “losna混合物” 对睾丸激素和雌二醇的分泌具有刺激作用。这些结果表明，即使是含有背景浓度的持久性有机污染物的混合物也会显着影响类固醇的分泌。与高剂量范围相比，低剂量范围内较高的类固醇生成反应表明异源生物调节功能。这可能会使风险评估中影响的预测复杂化。

BACKGROUND & AIMS: BACKGROUND:Transforaminal epidural steroid injection (TFESI) is a useful treatment modality for pain management. Most complications of TFESI are minor and transient. However, there is a risk of serious complications such as nerve injury, spinal cord infarct, or paraplegia. Some of the risks are related to direct injury to the vessel or intravascular injection of the particulate steroid. We prospectively tested the hypothesis that the intravascular injection rate of the Whitacre needle is lower than that of the Quincke needle during TFESI. METHODS:This study was a randomized trial of 1376 TFESIs at the S1 level. We collected data of age, gender, height, weight, laterality (right/left), history of lumbosacral spine operation, history of appropriate interval discontinuation of anticoagulation medicines, and underlying disease. During the S1 TFESI, intrasacral bone contact, a blood aspiration test, and real-time fluoroscopy of the intravascular injection using contrast media were investigated. RESULTS:There were no significant differences in the intravascular injection rate with respect to age, gender, height, weight, hypertension, diabetes mellitus, laterality, history of lumbosacral spine operation, or history of appropriate interval discontinuation of anticoagulation medicines. Intravascular injection was significantly associated with a blood aspiration test (P < 0.001), needle tip type (P = 0.002), intrasacral bone contact (P < 0.001), and physicians (some P < 0.05). The use of Quincke needles and intrasacral bone contact increased the rate of intravascular injection. CONCLUSIONS:To reduce the risk of intravascular injection, the use of Whitacre needles without intrasacral bone contact may be a safer and more effective approach.

背景与目标：

BACKGROUND & AIMS: Objective:Response to lumbar epidural steroid injection in lumbar radicular pain varies. The purpose of this study is to characterize the changes in quantitative sensory testing (QST) phenotypes of subjects and compare the QST characteristics in patients who do respond to treatment of radicular pain with a lumbar epidural steroid injection (ESI). Design:Prospective, observational pilot study. Setting:Outpatient pain center. Methods:Twenty subjects with a lower extremity (LE) radicular pain who were scheduled to have an ESI were recruited. At the visit prior to and four weeks following an ESI, subjects underwent QST measurements of both the affected LE and the contralateral unaffected UE. Results:Following an ESI, nine subjects reported a greater than 30% reduction in radicular pain and 11 reported a less than 30% reduction in radicular pain. Subjects who had less than 30% pain reduction response (nonresponders) to an ESI had increased pre-injection warm sensation threshold (37.30 °C, SD = 2.51 vs 40.39, SD = 3.36, P = 0.03) and heat pain threshold (47.22 °C, SD = 1.38, vs 48.83 °C, SD = 2.10, P = 0.04). Further, the nonresponders also showed increased pre-injection warm sensation threshold as measured in the difference of warm sensation detection threshold difference in the affected limb and the unaffected arm (2.68 °C, SD = 2.92 vs 5.67 °C, SD = 3.22, P  = 0.045). Other QST parameters were not affected. Conclusions:The results show that the nonresponders to ESIs have increased detection threshold to heat pain and warm sensation, suggesting that a preexisting dysfunction in the C fibers in this group of subjects who can be detected by QST. Such altered QST characteristics may prognosticate the response to ESIs.

背景与目标：