Dexamethasone potentiates in vitro blood-brain barrier recovery after primary blast injury by glucocorticoid receptor-mediated upregulation of ZO-1 tight junction protein

Owing to the frequent incidence of blast-induced traumatic brain injury (bTBI) in recent military conflicts, there is an urgent need to develop effective therapies for bTBI-related pathologies. Blood-brain barrier (BBB) breakdown has been reported to occur after primary blast exposure, making restoration of BBB function and integrity a promising therapeutic target. We tested the hypothesis that treatment with dexamethasone (DEX) after primary blast injury potentiates recovery of an in vitro BBB model consisting of mouse brain endothelial cells (bEnd.3). DEX treatment resulted in complete recovery of transendothelial electrical resistance and hydraulic conductivity 1 day after injury, compared with 3 days for vehicle-treated injured cultures. Administration of RU486 (mifepristone) inhibited effects of DEX, confirming that barrier restoration was mediated by glucocorticoid receptor signaling. Potentiated recovery with DEX treatment was accompanied by stronger zonula occludens (ZO)-1 tight junction immunostaining and expression, suggesting that increased ZO-1 expression was a structural correlate to BBB recovery after blast. Interestingly, augmented ZO-1 protein expression was associated with specific upregulation of the α⁺ isoform but not the α⁻ isoform. This is the first study to provide a mechanistic basis for potentiated functional recovery of an in vitro BBB model because of glucocorticoid treatment after primary blast injury.     

Key benefits of dexamethasone and antibody treatment in COVID-19 hamster models revealed by single-cell transcriptomics

1. Download : Download high-res image (199KB)
2. Download : Download full-size image

     

Dexamethasone as an adjuvant for peripheral nerve blockade: a randomised,triple-blinded crossover study in volunteers

Background

The efficacy of dexamethasone in extending the duration of local anaesthetic block is uncertain. In a randomised controlled triple blind crossover study in volunteers, we tested the hypothesis that neither i.v. nor perineurally administered dexamethasone prolongs the sensory block achieved with ropivacaine.

地塞米松促胎儿肺成熟的三种用药方式对母体糖代谢的影响

【目的】探讨地塞米松的用药方式对孕妇糖代谢的影响。【方法】对 1999年 9月至 2 0 0 1年 1月在本院住院的15 0名不同用药方式使用地塞米松促胎儿肺成熟的孕妇进行研究 ,在用药前及用药后 18～ 2 4h抽取肘前静脉血查空腹血糖、血浆C肽 ,糖负荷后 2h血糖、血浆C肽。【结果】使用地塞米松后 ,空腹血糖值、糖负荷后 2h血糖值、空腹C肽及糖负荷后 2hC肽值较用药前高 ;用药方式对母体空腹血糖值和空腹C肽值的影响差异无统计学意义 (P >0 0 5 ) ,对母体糖负荷后 2h血糖值和糖负荷后 2hC肽值的影响差异有统计学意义 (P <0 0 5 ) ;不同糖代谢状态的受试者使用地塞米松后 ,空腹C肽值、糖负荷后 2hC肽值的改变差异有统计学意义 (P <0 0 5 )。【结论】孕妇使用地塞米松促胎儿肺成熟对母体的糖代谢均有一定程度的影响 ,用药过程中和用药后需严密监测母体血糖和胎儿宫内状况     

Cosolvency of Dimethyl Isosorbide for Steroid Solubility

Dimethyl isosorbide (DMI), which is currently under investigation for its potential use as a pharmaceutical vehicle and drug permeation enhancer, is a water-miscible liquid with relatively low viscosity. The solubilization behavior of DMI as a cosolvent for nonpolar drugs was characterized via dielectric constant measurements of binary solvent systems containing DMI and either water, propylene glycol (PG), or polyethylene glycol (PEG). Evidence from the dielectric constant profiles and NMR studies suggest that DMI undergoes complexation with water and PG, but not with PEG, through hydrogen bonding interactions. The solvent complexation exhibited a major effect on the solubilities of prednisone, dexamethasone, and prednisolone in the mixed solvent systems. Maximum solubility of each drug was found to occur near a DMI/water or DMI/PG concentration ratio of 1:2. In the DMI–PEG mixed system, while there is no apparent interaction between DMI and PEG molecules, the solubility of prednisone was found to increase with decreasing dielectric constant.     

UPLC-MS/PDA检测中药制剂中醋酸泼尼松和醋酸地塞米松的研究

 目的建立快速、准确、高灵敏度的测定中药平喘制剂中醋酸泼尼松和醋酸地塞米松检测的方法。方法采用UPLC-MS/PDA法,以甲醇-0.01mol·L^-1醋酸铵(0.1%甲酸)缓冲溶液梯度洗脱,流速0.2mL·min^-1,离子源为ESI源,正离子检测,对中药制剂中非法添加醋酸泼尼松和醋酸地塞米松进行定性定量分析,并对其裂解途径进行解析。结果6批受试制剂中有2批分别检测到有醋酸泼尼松和醋酸地塞米松。结论此方法选择性强、灵敏度高,可作为分析中药制剂中醋酸泼尼松和醋酸地塞米松的有效检测方法。     

微量地塞米松与抗病毒药物合用对抗单疱病毒作用的影响

报告在组织培养中地塞米松对单纯疱疹病毒(HSV)的生长繁殖无影响,对无环鸟苷(ACV)和环胞苷(CC)的抗病毒作用亦无干扰。在动物实验中,微量地塞米松[0.001%,常用浓度(0.1%)的百分之一]并不恶化上皮型HSV角膜炎。同时证明有效抗病毒药物的合用,微量地塞米松仍保留有良好的消炎作用,能促进上皮型和实质层型单疱角膜炎的痊愈过程。     

地塞米松在大鼠缺血随意皮瓣中的作用

目的：研究局部使用地塞米松对大鼠缺血随意皮瓣的作用。方法：建立大鼠背部缺血随意皮瓣的动物模型，随机分为2组，实验组术后皮瓣下一次给予地塞米松5mg(用生理盐水稀释至3ml)，对照组术后皮瓣下一次给予0．9％生理盐水3ml。均于术后7d取材，测定皮瓣坏死率和组织中丙二醛含量，观察大体及病理切片。结果：实验组皮瓣坏死率和丙二醛含量较对照组显著降低(P＜0．01)。光镜下，实验组的炎性反应较对照组明显减轻。结论：地塞米松能提高缺血随意皮瓣的成活率，大剂量一次性给药的方法是可行的。     

Adrenocortical responsiveness in neonates weaned from the ventilator with dexamethasone

Adrenocortical responsiveness was assessed in eight very low birthweight neonates who had bronchopulmonary dysplasia and had been weaned from mechanical ventilation using dexamethasone. Three of the eight infants did not respond to ACTH stimulation during the first week after cessation of dexamethasone, but all three responded normally when retested at least 1 month later. The present authors have thus demonstrated that some infants have at least temporary adrenocortical unresponsiveness after prolonged courses of glucocorticoid therapy, and suggest that adrenocortical function should be assessed in all infants who are weaned from mechanical ventilation using dexamethasone.