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.     

腹腔镜胆囊切除术对胆道结石合并糖尿病患者肠屏障功能的影响

目的观察胆道结石合并糖尿病患者腹腔镜胆囊切除术(LC)后肠屏障功能的变化。方法将择期行LC的126例患者分为糖尿病组41例和非糖尿病组85例。术前及术后第1、3天,采用高效液相色谱法检测尿乳果糖与甘露醇比值(L/M),并采用酶联免疫吸附法(ELISA)检测尿脂肪酸结合蛋白(IFABP)及血清D-乳酸水平。结果2组患者均成功完成手术,无中转开放手术者。糖尿病组术后肛门排气时间长于非糖尿病组,差异有统计学意义(P<0.05)。糖尿病组术后第1、3天尿L/M、血清D-乳酸、尿IFABP均高于术前及非糖尿病组,差异均有统计学意义(P<0.05)。结论合并糖尿病的胆道结石患者行LC后会加重肠屏障功能障碍程度,术前控制好血糖水平或可降低肠道功能损伤的严重程度。     

Resveratrol attenuates high-fat diet-induced non-alcoholic steatohepatitis by maintaining gut barrier integrity and inhibiting gut inflammation through regulation of the endocannabinoid system

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1‐(2‐Hydroxyethyl)‐2‐imidazolidinone,a heparanase and matrix metalloproteinase inhibitor,improves epidermal basement membrane structure and epidermal barrier function

Daily exposure to sunlight is known to affect the structure and function of the epidermal basement membrane (BM), as well as epidermal differentiation and epidermal barrier function. The aim of this study is to clarify whether the inhibition of BM‐degrading enzymes such as heparanase and matrix metalloproteinase 9 (MMP‐9) can improve the epidermal barrier function of facial skin, which is exposed to the sun on a daily basis. 1‐(2‐hydroxyethyl)‐2‐imidazolidinone (HEI) was synthesized as an inhibitor of both heparanase and MMP‐9. HEI inhibited not only the BM damage at the DEJ but also epidermal proliferation, differentiation, water contents and transepidermal water loss abnormalities resulting from ultraviolet B (UVB). This was determined in this study by the use of UVB‐induced human cultured skins as compared with the control without HEI. Moreover, topical application of HEI improved epidermal barrier function by increasing water content and decreasing transepidermal water loss in daily sun‐exposed facial skin as compared with non‐treated skins. These results suggest that the inhibition of both heparanase and MMP‐9 is an effective way to care for regularly sun‐exposed facial skin by protecting the BM from damage.     

Myelopathy due to human T-cell leukemia virus type-1 from the donor after ABO-incompatible liver transplantation

We report the case of a 53-year-old-man who developed human T-cell leukemia virus type-1-associated myelopathy (HAM) after ABO-incompatible liver transplantation for alcoholic liver cirrhosis. The living donor was seropositive for human T-cell leukemia virus type-1 (HTLV-1) and the recipient was seronegative for HTLV-1 before transplantation. After transplantation, the recipient developed steroid-resistant acute cellular rejection, which was successfully treated using anti-thymocyte globulin, and he was eventually discharged. He underwent spinal surgery twice after the transplantation for the treatment of cervical spondylosis that had been present for a period of 9 months before the transplantation. The surgery improved his gait impairment temporarily. However, his gait impairment progressed, and magnetic resonance imaging revealed multiple sites of myelopathy. He was diagnosed with HAM 16 months after the transplantation. Pulse steroid therapy (1000 mg) was administered over a period of 3 days, and his limb paresis improved. Presently, steroid therapy is being continued, with a plan to eventually taper the dose, and he is being carefully followed up at our institution. Our case suggests that liver transplantation involving an HTLV-1-positive living donor carries the risk of virus transmission and short-term development of HAM after transplantation.     

芪地固肾方治疗特发性膜性肾病的临床分析

目的:回顾性分析芪地固肾方治疗特发性膜性肾病(IMN)的临床疗效与安全性。方法:选取2014年1月至2017年6月陕西中医药大学附属医院肾病科门诊及住院IMN患者141例,根据用药方案分为西药组(西药标准疗法)、中西药结合组(芪地固肾方+西药标准疗法)和中药组(芪地固肾方)3组各47例,观察3组患者治疗后临床疗效、复发率及不良反应等。结果:治疗6个月后,中西药结合组和西药组总有效率72.34%、68.09%高于中药组,治疗12个月时3组有效率比较差异无统计学意义,治疗18个月后中药组和中西药结合组总有效率75.76%、78.72%高于西药组。中药组和中西药结合组在治疗12个月和18个月后较西药组在提高中医证候疗效、减少中医证候积分上更具优势。中药组和中西药结合组复发率更低,3组均未出现严重不良反应。结论:芪地固肾方能提高IMN缓解率,在提高中医证候疗效、降低复发率上更具优势,远期疗效可观,值得进一步推广应用。