Aldosterone receptor sites on plasma membrane of human vascular endothelium detected by a mechanical nanosensor

The mineralocorticoid hormone aldosterone acts on target cells of kidney, colon, and the cardiovascular system through genomic and nongenomic pathways. Although the classical intracellular mineralocorticoid receptor plays a key role in mediating both pathways, it is unclear whether there are specific aldosterone receptors located on the cell surface. To search for such sites in vascular endothelium, we used an atomic force microscope (AFM) which measures unbinding forces based on single molecular recognition between an aldosterone-loaded AFM tip and the cell membrane. Aldosterone was tethered covalently via linker molecules to an AFM tip. Human endothelial cells (EA.hy926) were grown in culture and studied in buffer at 37°C. Using the aldosterone-functionalized AFM tip as a mechanical nanoscale indenter, unbinding forces could be measured at randomly chosen sites of the plasma membrane. Sites with strong interactions between AFM tip and cell surface could be identified exhibiting unbinding forces of about 65 pN. The binding probability between the aldosterone-loaded tip and the cell surface at selected membrane sites was 53 ± 7.2%. Addition of an excess supply of aldosterone to the bath solution blocked the binding of the aldosterone-loaded tip to the cell surface. The binding probability was reduced to 8.0 ± 1.8% when an excess supply of aldosterone was added to the bath. However, it was not influenced by the addition of spironolactone or dexamethasone. We conclude that aldosterone receptor sites exist on the cell surface of vascular endothelial cells distinct from the classical mineralocorticoid receptors and insensitive to glucocorticoids. Binding of aldosterone to these receptors initiates an intracellular signaling cascade that precedes the classical genomic response and most likely participates in the control of vascular resistance.     

糖皮质激素对甲醛致炎大鼠c-fos表达的影响

目的为糖皮质激素(GCS)对神经细胞的作用提供形态学资料。方法30只SD大鼠随机分为:对照组、单纯甲醛组、地塞米松预处理组、RU486预处理组、RU486+地塞米松预处理组,甲醛刺激后采用动物行为学方法、免疫组织化学法、神经细胞染色和形态计量学方法进行观察。结果在大鼠后爪掌面皮下注射稀释甲醛20μl可造成注射处急性持续性炎症。1h后,同侧脊髓腰膨大背角浅层。双侧中缝大核、丘脑、大脑皮层Fos免疫阳性神经元(FLI)总数明显上升,对侧脊髓内少量散在分布。用地塞米松预处理2h后可使相应部位FLI神经元数明显降低,具有剂量依赖性。外周水肿。疼痛表现与同侧背角浅层FLI细胞数呈正相关。用糖皮质激素受体阻断剂RU486可部分反转GCS的效应。结论伤害性刺激可引起中枢神经系统c-fos广泛表达。GCS可降低脊髓后角神经元的兴奋性。     

地塞米松麻黄素混合液滴鼻预防高压氧治疗突发性聋继发的中耳气压伤

目的探讨地塞米松麻黄素混合液滴鼻预防高压氧治疗突发性聋继发中耳气压伤的应用价值。方法回顾性分析2016年1月~2019年12月确诊为突发性聋并接受高压氧治疗的368例(392耳)患者的临床资料,其中190例(204耳)为观察组,高压氧治疗前给予地塞米松麻黄素混合液滴鼻联合山楂、陈皮咀嚼;178例(188耳)为对照组,治疗前不给予地塞米松麻黄素滴鼻,比较两组患者治疗效果、继发中耳气压伤情况。结果治疗后两组纯音听阈均较治疗前改善,差异有统计学意义(均为P<0.05),但观察组与对照组间总有效率(分别为91.18%和88.30%)差异无统计学意义(P>0.05)。两组共38例(42耳)发生中耳气压伤,观察组中耳气压伤发生率(6.8%,14/204)和损伤程度均低于对照组(14.8%,28/188),差异有统计学意义(P<0.05)。38例继发中耳气伤病例中,32例(84.21%,32/38)存在鼻腔鼻咽部或/和咽后壁不同程度病变(下鼻甲肥大、鼻息肉、鼻咽部淋巴组织增生等),28例(73.68%,28/38)(30耳)有中耳功能异常(鼓室导抗图As型8耳,Ad型6耳,B型6耳,C型10耳)。结论地塞米松麻黄素混合液滴鼻联合山楂陈皮咀嚼可有效降低突发性聋患者高压氧治疗继发中耳气压伤的发生率及损伤程度。     

流行性腮腺炎病毒性脑膜炎短程高效治疗临床观察

目的：探讨流行性肋腺炎病毒性脑膜炎（肋脑）短程高效的治疗方法。方法：以临床和实验室确诊的155例肋脑患者为观察组，采用地塞米松一次性鞘内注射治疗方法，并与同期入院的常规对症治疗组对照。结果：观察组退热时间、头痛和脑膜刺激症状消失时间及治愈时间分别是32h、15h、12h、3．1d，明显优于对照组的58h、24h、32h、6.5d，且差异有非常显著性或差异有显著性（P＜0．01或0．05）。结论：地塞米松一次性鞘内注射疗法治疗肋脑短程、高效，安全。     

Dexamethasone loaded bioresorbable films used in medical support devices: structure, degradation, crystallinity and drug release

Bioresorbable polymer films containing dexamethasone (DM) were prepared using a solution processing technique. Investigation of the films focused on cumulative DM release as affected by film morphology (drug location/dispersion in the film) and degradation processes. Two film structures were studied: A-type, a polymer film with large drug crystals located on the film’s surface, and B-type, a polymer film with small drug particles and crystals distributed within the bulk. The effect of the polymer’s degree of crystallinity on the drug release profile was also studied. Prototypical applications of these films are biodegradable medical support devices which combine mechanical support with drug release. In most of our studied systems the drug release profile from the film is determined mainly by both drug location/dispersion in the film and the polymer’s weight loss rate. All release profiles from A-type films exhibited a burst effect of approximately 30%, accompanied by a second release phase at a constant rate, whereas the release profiles from B-type films were determined mainly by the degradation profile of the host polymer, and did not exhibit any burst effect. A high degree of crystallinity is important for the current application, since good mechanical properties are required. This contributes to slower drug release rates, mainly at relatively low weight losses, whereas at high weight losses, where a porous structure is created, the crystallinity almost does not affect the rate of drug release. The shape of the porous structure that develops with degradation also affects the drug release profile from the B-type films.     

急性肺血栓栓塞症兔TNF-α、IL-8、IL-10水平及地塞米松的影响

目的:探讨兔急性肺血栓栓塞症(PTE)时血浆及支气管肺泡灌洗液(BALF)中TNF-α,IL-8、IL-10的水平和地塞米松(Dex)的影响。方法:采用自体血栓回输法建立兔急性PTF模型。36只兔随机分为对照组、Dex治疗组和PTE模型组。用ELISA方法检测上述细胞因子(CK)水平,术毕肺组织行病理观察。结果:栓塞后上述CK均有升高,治疗后TNF-α、IL-8均有下降,IL-10变化不明显。组织病理学可见栓塞后肺动脉内血栓形成,肺组织萎缩、出血、炎性反应明显,Dex治疗后肺组织病理改变明显减轻。结论:PTE后促炎性CK在引起肺部炎性反应和肺组织及肺动脉病损中起了重要作用,抗炎治疗可以明显减轻CK引起的这种损伤。抗炎治疗能降低PTE急性期病死率,改善远期预后,CK可能起了很重要的作用。     

丁二磺酸腺苷蛋氨酸联合地塞米松对妊娠期肝内胆汁淤积症患者免疫功能及疗效的影响

目的：探讨丁二磺酸腺苷蛋氨酸联合地塞米松对妊娠期肝内胆汁淤积症（ＩＣＰ）患者免疫功能及疗效的影响。方法：选取2013年9月—2015年9月住院的ICP患者78例,将所有研究对象分为观察组与对照组,各39例,对照组采用丁二磺酸腺苷蛋氨酸治疗,观察组采用丁二磺酸腺苷蛋氨酸联用地塞米松联合治疗。比较2组治疗前后血清总胆汁酸（TBA）、总胆红素（TBIL）、直接胆红素（DBIL）、谷丙转氨酶（ALT）、谷草转氨酶（AST）、白细胞介素12（IL-12）及肿瘤坏死因子α（TNF-α）水平,比较2组产后胎盘组织中TNF-α的表达水平及治疗效果。结果：观察组的治疗效果优于对照组,妊娠结局与围生儿状况同样优于对照组（P＜0.05）。2组患者治疗后TBA、TBIL、ALT、AST及IL-12水平均明显下降（P＜0.05）,且观察组较对照组下降更明显（P＜0.05）。观察组DBIL、TNF-α及产后胎盘TNF-α水平均低于对照组,观察组各指标治疗前后差值均高于对照组（P＜0.05）。结论：丁二磺酸腺苷蛋氨酸联合地塞米松治疗ICP,在缓解患者临床体征、降低血胆汁酸及改善肝功能等方面有显著的临床效果,并可改善患者的免疫功能状态、妊娠结局及围生儿状况。     

地塞米松鼓室注射对突发性聋患者的影响

目的探讨地塞米松鼓室注射后对突发性聋患者内耳微循环的影响。方法研究组34例（35耳）突发性聋患者采用地塞米松静脉给药基础上加用鼓室内注射地塞米松治疗;对照组34例（34耳）仅采用地塞米松静脉给药治疗。结果研究组痊愈12耳,显效10耳,好转10耳,无效3耳。对照组痊愈7耳,显效8耳,好转10耳,无效9耳。治疗组有效率为91．4％。对照组有效率为71．4％。经统计学处理两组有差异（P〈0．05）。结论地塞米松鼓室注射后可明显改善突发性聋患者内耳微循环。     

地塞米松诱导红系细胞凋亡的观察

以ＦＶＡ病毒诱导ＢＡＬＢ／ｃ小鼠脾细胞形成的红系细胞（ｅｒｙｔｈｒｏｉｄｃｅｌ）为研究对象，在红系细胞凋亡抑制剂——红细胞生成素（ＥＰＯ）存在情况下，观察了地塞米松（Ｄｅｘ）对上述细胞凋亡的诱导作用。结果表明，在一定浓度范围内，随着Ｄｅｘ作用时间的延长，细胞逐步凋亡并出现特有的ＤＮＡ梯形（ＤＮＡｌａｄｄｅｒ），而且其ＤＮＡ断裂程度与Ｄｅｘ的作用浓度呈正相关。透射电镜的结果证实，经最适浓度（５×１０－５ｍｏｌ／Ｌ）Ｄｅｘ处理后，红系细胞出现核固缩，染色质凝聚，核周隙扩大，核破裂，胞浆近膜处出现空泡以及细胞破碎等程度不同的细胞凋亡特征。说明Ｄｅｘ可拮抗ＥＰＯ的作用，有效地诱导红系细胞凋亡     

ACTH-producing cells of 21-day-old rat fetuses after maternal dexamethasone exposure

Adrenocorticotrophic hormone (ACTH) is essential for developmental maturation of numerous organ systems during the fetal period and for adaptation to environmental challenges. Immunocytochemical and stereological methods were used in the present study to examine the effects of dexamethasone (Dx) administration during pregnancy on fetal rat pituitary ACTH-producing cells. Doses of 0.5, 0.5 and 1.0 mg Dx/kg body weight/day were given to the dams on 3 consecutive days starting on day 16 of gestation. Morphometric analysis of the ACTH-producing cells of fetuses at 21 days of gestation revealed significant inhibition by 24% and 27%, respectively, of cell volume and cell number after maternal Dx administration, whereas the volume of cell nuclei and volume density of ACTH-stained cells were insignificantly decreased. Immunocytochemical analysis showed reduced numbers, sizes and immunopositivity of ACTH cells of 21-day-old fetuses from Dx-treated dams as compared with the control group. Maternal Dx treatment in the period of intense differentiation of the hypothalamo-hypophyseal-adrenal system had an inhibitory effect on fetal function and proliferative activity of ACTH-producing cells at 21 days of gestation. Thus, inhibition of activity of fetal ACTH-producing cells may lead to adrenal suppression, modified activity of the hypothalamo-pituitary-adrenal axis and reduced body weight possibly causing lasting functional abnormalities.