沙美特罗替卡松粉剂在慢性阻塞性肺疾病稳定期应用的临床观察

目的观察长期吸入沙美特罗替卡松粉剂对于稳定期中重度慢性阻塞性肺疾病（COPD）患者肺功能及生活质量的影响。方法将50例COPD稳定期患者随机分为两组。治疗组长期给予沙美特罗替卡松粉剂2次/d,每次1吸;对照组仅在急性发作期吸入沙美特罗替卡松粉剂1,年后比较两组肺功能、呼吸困难指数、急性发作次数及平均入院天数。结果①治疗组一年后FEV1及FVC较对照组有明显改善;②治疗组呼吸困难明显改善;③治疗组急性发作次数及住院天数均少于对照组。结论对于稳定期中重度COPD患者长期吸入沙美特罗替卡松粉剂可改善肺功能及生活质量。     

Ammonia metabolism,the brain and fatigue; revisiting the link

This review addresses the ammonia fatigue theory in light of new evidence from exercise and disease studies and aims to provide a view of the role of ammonia during exercise. Hyperammonemia is a condition common to pathological liver disorders and intense or exhausting exercise. In pathology, hyperammonemia is linked to impairment of normal brain function and the onset of the neurological condition, hepatic encephalopathy. Elevated blood ammonia concentrations arise due to a diminished capacity for removal via the liver and lead to increased exposure of organs, such as the brain, to the toxic effects of ammonia. High levels of brain ammonia can lead to deleterious alterations in astrocyte morphology, cerebral energy metabolism and neurotransmission, which may in turn impact on the functioning of important signalling pathways within the neuron. Such changes are believed to contribute to the disturbances in neuropsychological function, in particular the learning, memory, and motor control deficits observed in animal models of liver disease and also patients with cirrhosis. Hyperammonemia in exercise occurs as a result of an increased production by contracting muscle, through adenosine monophosphate (AMP) deamination (the purine nucleotide cycle) and branched chain amino acid (BCAA) deamination prior to oxidation. Plasma concentrations of ammonia during exercise often achieve or exceed those measured in liver disease patients, resulting in increased cerebral uptake. In this article we propose that exercise-induced hyperammonemia may lead to concomitant disturbances in brain function, potentially through similar mechanisms underpinning pathology, which may impact on performance as fatigue or reduced function, especially during extreme exercise.     

Gender differences in the expression of galanin and vasoactive intestinal peptide in oestrogen-induced prolactinomas of Fischer 344 rats

We have previously described a sexual dimorphism in oestrogen-induced anterior pituitary tumorigenesis in Fischer 344 rats, with female tumours averaging twice the size of those of males. Neonatal androgenization of female Fischer 344 rats with 100 micro g of testosterone propionate reverted that effect, causing a 'male-like' phenotype. The peptides galanin and vasoactive intestinal peptide (VIP) are possible mediators of oestrogen effects on the anterior pituitary, including hyperprolactinemia and lactotroph proliferation. To further extend our previous findings, we investigated the expression of galanin and VIP in the anterior pituitary of control and oestrogenized male, female and neonatally androgenized female Fischer 344 rats. At 3 months of age, rats were deprived of their gonads and divided into control and diethylstilbestrol (DES)-treated groups. In the anterior pituitary of control rats, galanin and VIP immunoreactive cells were absent. However, in DES-treated rats, pituitaries from normal ovariectomized females showed higher number of galanin and VIP positive cells than pituitaries from neonatally androgenized ovariectomized females and gonadectomized males. This pattern correlated with changes in anterior pituitary weight and serum prolactin. Our study suggests that sexual differences in oestrogen-induced pituitary tumorigenesis could be due to the differential expression of galanin and VIP. Furthermore, our data support the fact that neonatal exposure to androgens, as in normal males and androgenized females, may condition the response of the pituitary gland to oestrogens in adult life.     

Early onset vulvar Lichen Sclerosus in premenopausal women and oral contraceptives

OBJECTIVE: For vulvar Lichen sclerosus (LS) immunological factors, genetic predisposition, and decreased 5 alpha-reductase activity have been discussed as aetiological factors. During the last decade an increase of LS in young women has been suspected. Aim of this study was to evaluate data of premenopausal women with early onset LS to find potential risk factors focussing on the use of oral contraceptives. STUDY DESIGN: We retrospectively analyzed the data of 40 premenopausal patients with early onset LS regarding use of oral contraceptives (OCPs), and first occurrence of LS. To compare these data in a case-control study we analyzed a matched control group of 110 healthy women. RESULTS: All our LS patients were using OCPs compared to 73 women (66.4%) in the control group. OCPs with anti-androgenic activity (chlormadinone acetate, cyproterone acetate, dienogest, and drospirenone) were used by 28 (70%) of the LS patients and by 35 (47.9%) of the 73 women using OCPs in the control group. Thus, the odds ratio for early onset LS for women using anti-androgenic OCPs was 2.53 (95% CI: 1.12-5.75). CONCLUSION: Our data suggest that disturbance of the androgen dependent growth of the vulvar skin by OCPs and especially by OCPs with anti-androgenic properties might trigger the early onset of LS in a subgroup of susceptible young women.     

不同诱导因子对 MT-5细胞表达 HBsAg 的影响

对经 HBV-DNA 转染的 MT-5细胞的培养条件进行观察。发现重金属离子Zn 和 Cd 对 MT-5细胞表达 HBsAg 有诱导作用,而咖啡因、地塞米松、氢化可的松、丙酸睾丸酮、苯丙酸诺龙对 MT-5细胞的 HBsAg 均无诱导作用。     

沙美特罗/丙酸氟替卡松干粉剂吸入治疗成人支气管哮喘60例疗效观察

目的:探讨沙美特罗/丙酸氟替卡松干粉剂(商品名:舒利迭,葛兰素史克公司出品)吸入治疗支气管哮喘的疗效。方法:90例患者随机分为2组,治疗组采用沙美特罗/丙酸氟替卡松干粉剂50/250"g每日2次吸入,对照组采用丙酸氟替卡松气雾剂(商品名:辅舒酮,葛兰素史克公司出品)250"g每日2次吸入,治疗第4、8周两次评价患者哮喘症状和疗效。结果:在治疗第4、8周,治疗组哮喘症状和对照组相比明显减轻。结论:舒利迭为沙美特罗/丙酸氟替卡松混合吸入剂,是控制哮喘的一个良好选择。     

沙美特罗替卡松在哮喘治疗中的控制作用

目的研究沙美特罗替卡松粉吸入剂治疗支气管哮喘的临床安全性及疗效。方法选择2009年2～10月笔者所在医院110例支气管哮喘患者,随机分成治疗组和对照组,每组各55例。治疗组患者选择沙美特罗替卡松粉吸入剂治疗;对照组患者只选择丙酸氟替卡松进行治疗,观察两组患者药物反应和症状改善情况,比较两组患者咳嗽、喘息及呼吸困难消失时间。结果治疗组患者咳嗽、喘息及呼吸困难消失时间都比对照组患者短,差异有统计学意义（P〈0.05）;治疗组用药后各项肺功能改变率与对照组比较,差异有统计学意义（P〈0.05）。结论应用沙美特罗替卡松粉吸入剂治疗哮喘,不但治疗效果好而且使用安全,值得临床上推广应用。     

从运动神经元的TDP-43蛋白表达和ADAR2活性探讨肌萎缩侧索硬化症的发病机制

肌萎缩性侧索硬化症(ALS)是以上下两级运动神经元进行性丢失为特征的神经系统变性疾病,是运动神经元病(MND)中最常见的类型。运动神经元中的病理性TDP-43是ALS的病理特征。此外,散发性ALS运动神经元中作用于RNA的次黄嘌呤腺苷脱氢酶(ADAR2)减少、具有未经编辑Q/R位点的谷氨酸受体2(GluR2)表达增加,α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体(AMPAR)属性受影响,Ca2+通透性增加,Ca2+流入胞质增加导致神经元死亡。ALS运动神经元死亡包含病理性TDP-43和ADAR2活性下降,两种病理变化可能在细胞死亡中存在一定联系。ADAR2 mRNA是TDP-43蛋白的靶RNA,TDP-43蛋白在ADAR2的表达中起调节作用。近年来,研究者探讨ALS的基因治疗可能性:动物实验结果提示,外周静脉给予9型腺相关病毒载体(AAV9),可上调鼠运动神经元ADAR2,引发外源性ADAR2在中枢神经元表达,从而有效防治运动功能障碍。运动神经元的获救可能与TDP-43基因的正常表达有关。AAV9介导的ADAR2基因植入可能为ALS的基因治疗提供新的前景。     

Topical hydrocortisone,clobetasol propionate,and calcipotriol do not increase photocarcinogenesis induced by simulated solar irradiation in hairless mice

Please cite this paper as: Topical hydrocortisone, clobetasol propionate, and calcipotriol do not increase photocarcinogenesis induced by simulated solar irradiation in hairless mice. Experimental Dermatology 2010; 19 : 973–979. Abstract: Topical corticosteroids such as hydrocortisone‐17‐butyrate (HCB) and clobetasol‐17‐propionate (CP) and vitamin D₃ derivatives such as calcipotriol (CAL) are widely used to treat psoriasis. The immunosuppressive effects of corticosteroids make their topical use a concern for skin carcinogenicity. Few studies have assessed the effect of topical corticosteroids and topical vitamin D₃ derivatives on photocarcinogenesis induced by ultraviolet radiation. We investigated whether HCB, CP, or CAL can accelerate photocarcinogenesis using simulated solar radiation (SSR). HCB, CP, or CAL was applied topically to the backs of hairless, female, C3.Cg/TifBomTac‐immunocompetent mice in 16 groups of 25 mice each. The drugs were applied three times weekly followed by 0, 2, 4, or 6 standard erythema doses (SED) of SSR for 365 days or until death. No change was observed in the time required for tumor development in mice treated with HCB and 2 SED (HCB‐2SED) and HCB‐6SED. However, the time required for tumor development increased with HCB‐4SED treatment. Treatment with CP‐2SED did not change the time to onset of the first and second tumor, but all other CP treatments in combination with SSR increased the time. CAL‐2SED decreased the time to onset of the first tumor but not of the second and third tumor. CAL‐4SED and CAL‐6 SED did not change or increased the time to tumor development. Our data indicated that topical administration of HCB and CAL did not alter the photocarcinogenesis of SSR and that topical CP administration had a photoprotective effect. Thus, HCB, CP, and CAL do not increase photocarcinogenesis induced by SSR.     

高效液相色谱法测定复方丙睾软膏中丙酸睾丸素含量

目的测定复方丙睾软膏中丙酸睾丸素含量。方法色谱柱为C18(250 mm×4.6 mm,5μm),流动相为甲醇-水(80∶20),流速为1.0 mL.min-1,检测波长241 nm。结果丙酸睾丸素在1~100μg.mL-1中线性关系良好(r=0.999 9),回收率大于95%,Rsd小于1%。结论该法灵敏、简便、准确,可作为本品的定量分析方法。