高压氧联合地塞米松治疗突发性耳聋的疗效及相关影响因素分析

目的 分析高压氧联合地塞米松治疗突发性耳聋（SD）的疗效及相关影响因素。方法 回顾性分析 2014年 1 月—2016 年 12 月我院 200 例采用高压氧联合地塞米松治疗的 SD 患者的临床资料，根据疗效分为有效组（n=182 例）与无效组（n=18 例），比较 2 组性别、年龄、发病至就诊时间、耳别、听力损失、听力曲线类型、伴眩晕情况、伴耳鸣情况、合并疾病（高血压或糖尿病）、血浆黏度及血清 C 反应蛋白（CRP）等指标，并采用 Logistic 回归筛选影响SD 疗效的危险因素。结果 200 例患者经治疗后，总有效 182 例（91.00%），无效 18 例(9.00%）。有效组年龄>50岁、发病至就诊时间>7 d、听力损失≥60 dB、听力曲线类型为高频型或全聋型、伴眩晕、合并高血压、合并糖尿病、血浆黏度≥2 mPa·s、血清 CRP≥20 μmol/L 的比例明显低于无效组（P＜0.05）。Logistic 回归分析显示，年龄（>50 岁）、发病 至就诊时间（>7 d）、听力损失（≥60 dB）、听力曲线类型为高频型或全聋型、伴眩晕、合并高血压、合并糖尿病、血浆黏度（≥2 mPa·s）、血浆 CRP（≥20 μmol/L）为影响 SD 疗效的危险因素（P＜0.05）。结论 高压氧联合地塞米松是治疗SD 的有效方案，但影响其疗效的因素众多，临床治疗时有必要考虑患者临床与病理特征。     

Proteasome inhibition in hematologic malignancies

Hematologic malignancies, including multiple myeloma (MM), will account for more than 100,000 new cases of cancer and over 57,000 deaths in the United States in 2003. Treatment of MM is a serious challenge, because despite a variety of available therapies, median survival is short. A new therapeutic area focuses on inhibiting the activity of the proteasome, a 26S protease complex involved in cell cycle regulation, cell adhesion, inflammation, and protein turnover. The novel proteasome inhibitor, bortezomib (Velcade®), was recently approved for use in patients with refractory and relapsed MM and to date is the only proteasome inhibitor to have entered clinical trials. Bortezomib has demonstrated activity with manageable toxicity in a variety of hematologic malignancies in addition to MM, including leukemia and non‐Hodgkin's lymphoma. This article reviews clinical information on bortezomib in hematologic malignancies both as monotherapy and in combination with dexamethasone. Preliminary reports of bortezomib in combination with Doxil (pegylated liposomal doxorubicin), melphalan, and thalidomide are discussed, and current trials are described. Available data suggest that bortezomib will be useful in the treatment of a variety of hematologic malignancies.     

Separation of Hemoglobin a and F by Cation Exchange Dextran Gels

Two new cation exchange gels, SE-Sephadex C-50 and CM-Sephadex C-50, have been used to separate fetal and adult hemoglobins.

The separation obtained with CM-Sephadex was complete in spite of the relatively high flow rates used.     

The use of intraocular corticosteroids

Background: Diabetic macular edema (DME), cystoid macular edema (CME), age-related macular degeneration (AMD), retinal vascular occlusion (RVO) and uveitis are responsible for severe visual impairment worldwide. In some patients with these conditions, treatment with intraocular corticosteroids may be beneficial. Although off-label use of these agents has occurred for many years, novel agents including preservative-free and sustained-release intravitreal implants are currently being studied in clinical trials (CTs). Objective: To review the use of intraocular corticosteroids. Methods: Literature review. Results: Used alone, intravitreal corticosteroids may benefit disorders such as DME, RVO and uveitis compared with standard therapy or observation. Patients with AMD may benefit more from combination treatment with photodynamic therapy, intravitreal corticosteroid and intravitreal anti-VEGF injections. Intraoperative use of these agents may assist in visualization and manipulation of fine retinal structures. Sustained-release intraocular implants have been approved for severe posterior uveitis, and have shown benefits in ongoing CTs. Conclusion: Although intraocular corticosteroid injections have a limited duration of action requiring frequent re-treatment, and significant side effects including cataract and glaucoma development, intraocular injections may be of benefit in certain ocular disorders. Corticosteroid implants are emerging as potential treatments for macular edema due to uveitis, DME or RVO.     

Pharmacotherapy for treatment of retinal vein occlusion

Introduction: Retinal vein occlusion (RVO) is a common vascular condition, which may cause blindness and impaired vision as a result of the development of macular oedema. The management of macular oedema due to RVO is complex and a multidisciplinary approach is required in order to limit disease progression and achieve a better clinical outcome.

Areas covered: An update and a brief review on the current treatment strategies were provided in patients with macular oedema following RVOs. Evidence available from prospective, multicentre clinical studies evaluating the use of VEGF inhibitors and steroids and from a selective literature search is reported.

Expert opinion: For many years, laser photocoagulation has been considered the standard of care for the treatment of branch RVO. However, new treatment modalities have been evaluated through randomised controlled trials. Recently, anti-VEGF agents and corticosteroids have been shown to be efficacious options in the treatment of RVO.     

Dexamethasone-induced apoptosis in PC12 cells

Abstract

This study aims to evaluate the cytotoxicity and damage of dexamethasone (DEX) on rat pheochromocytoma (PC12) cells by determining cell viability, Hoechst 33342 staining, mitochondrial depolarization assays, opened mitochondrial permeability transition pores (MPTPs) detection, and measurement of Caspase-3 and Bcl-2 activities. The results show that DEX inhibits PC12 cell growth and decreases their viability in a remarkable dose-dependent manner. Our results also reveal that DEX exposure causes morphologic changes, opening of MPTPs and mitochondrial depolarization, upregulates Caspase-3 expression, and suppresses Bcl-2 expression in PC12 cells. These results suggest that DEX-induced apoptosis may be mediated through mitochondrial dysfunction.     

Dexamethasone for ocular inflammation

Introduction: Corticosteroids, administered systemically and periocularly, have long been used to treat intermediate and posterior segment noninfectious uveitis. In addition to systemic immunosuppressive medications, these therapies are used to reduce inflammation, prevent structural complications and prevent long-term visual loss in patients with uveitis. While systemic immunosuppressive therapies carry their own set of side effects, treatment with local steroids is associated with the risk of development of cataract and glaucoma.

Areas covered: Intravitreal delivery of fluocinolone acetonide via a sustained-release implant (Retisert) was approved by the FDA in 2005 for the treatment of noninfectious intermediate and posterior uveitis. Recently, the FDA also approved the biodegradable dexamethasone implant (Ozurdex) for the treatment of noninfectious uveitis involving the posterior segment.

Expert opinion: The single injection, 26-week data indicate that the implant is well tolerated and produces meaningful improvements in intraocular inflammation and visual acuity that persist through 6 months. The available 6-month data also indicate that this implant confers much less of a risk of ocular hypertension than other forms of intraocular steroid therapy. However, future longer-term trials are needed to evaluate the efficacy and safety data in patients who receive multiple injections. The newly approved dexamethasone implant, Ozurdex, is a useful addition to our local armamentarium in the treatment of noninfectious intermediate and posterior uveitis given its efficacy, safety, and ease of use in the outpatient setting.     

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.