Melatonin exacerbates acute experimental autoimmune encephalomyelitis by enhancing the serum levels of lactate: A potential biomarker of multiple sclerosis progression

Melatonin has a beneficial role in adult rat models of multiple sclerosis (MS). In this study, melatonin treatment (10 mg/kg/d) was investigated in young age (5‐6 weeks old) Lewis rat model of acute experimental autoimmune encephalomyelitis (EAE) followed by assessing serum levels of lactate and melatonin. Results showed that clinical outcomes were exacerbated in melatonin‐ (neurological score = 6) vs PBS‐treated EAE rats (score = 5). Melatonin caused a significant increase in serum IFN‐γ, in comparison to PBS‐treated EAE rats whereas no considerable change in IL‐4 levels were found, although they were significantly lower than those of controls. The ratio of IFN‐γ/IL‐4, an indicator of Th‐1/Th‐2, was significantly higher in PBS‐ and melatonin‐ treated EAE rats, in comparison to controls. Moreover, results showed increased lymphocyte infiltration, activated astrocytes (GFAP+ cells) but also higher demyelinated plaques (MBP‐deficient areas) in the lumbar spinal cord of melatonin‐treated EAE rats. Finally, serum levels of lactate, but not melatonin, significantly increased in the melatonin group, compared to untreated EAE and normal rats. In conclusion, our results indicated a relationship between age and the development of EAE since a negative impact was found for melatonin on EAE recovery of young rats by enhancing IFN‐γ, the ratio of Th1/Th2 cells, and astrocyte activation, which seems to delay the remyelination process. While melatonin levels decline in MS patients, lactate might be a potential diagnostic biomarker for prediction of disease progression. Early administration of melatonin in the acute phase of MS might be harmful and needs further investigations.     

Evaluation and Treatment of Acute and Subacute Hearing Loss: A Review of Pharmacotherapy

Among various forms of hearing loss, there are acute (within 72 hrs) or subacute (weeks to months) presentations that may be reversible with early pharmacological intervention. The workup of a patient presenting with hypoacusia includes the usual history and physical examination in conjunction with an audiometric assessment in order to categorize the hearing loss as conductive, sensorineural, or mixed. Sudden sensorineural hearing loss and autoimmune inner ear disease are acute and subacute forms of sensorineural hypoacusia most likely to be reversed with prompt pharmacological intervention. Systemic or local corticosteroid therapy has the most evidence of benefit in patients with sudden sensorineural hypoacusia and is the best available first line therapy noted in clinical practice guidelines. Alternative immunosuppressant therapies have not been well studied, and many have serious toxicities that further complicate the benefit‐risk assessment. There are no randomized comparisons of corticosteroid dosing regimens that evaluated clinically important outcomes, so expert opinion must serve as the basis for dosing recommendations. Clinicians need to involve patients with hypoacusia in the shared decision‐making process, since partial or complete reversal of hearing loss can have substantial quality‐of‐life implications for affected patients.     

大黄素对自身免疫性甲状腺炎小鼠的作用机制研究*

目的 探讨大黄素治疗自身免疫性甲状腺炎（AT）小鼠的作用机制。方法 选择60只小鼠随机 分为正常组、模型组和实验组,每组20只。实验组给予75 mg/kg 大黄素灌胃,对照组和模型组灌胃等剂量 生理盐水,均1次/d,连续8周。采用酶联免疫吸附试验测定甲状腺球蛋白抗体（TGAb）和甲状腺过氧化物 酶自身抗体（TPOAb） 水平;观察甲状腺淋巴细胞浸润程度;采用流式细胞术测定T 淋巴细胞亚群变化。 结果 正常组、模型组和实验组小鼠血清TGAb 和TPOAb 水平比较,差异有统计学意义（P <0.05）;实验组 低于模型组（P <0.05）。3 组小鼠淋巴细胞浸润程度比较,差异有统计学意义（P <0.05）;实验组低于模型组 （P <0.05）。3 组小鼠CD3+CD4+和CD3+CD8+比较,差异有统计学意义（P <0.05）;实验组低于模型组 （P <0.05）。结论 大黄素可下调AT 小鼠血清TGAb 和TPOAb 水平,减轻淋巴细胞浸润程度,调节小鼠免 疫功能。     

结核分枝杆菌感染合并自身免疫性疾病的研究进展

结核病和自身免疫性疾病,临床表现多有重叠、相似且容易合并发生,造成鉴别诊断及评估困难,容易造成误诊、漏诊及延误诊断,影响治疗。两者合并常常累及全身多系统、器官,病情较重,治疗复杂,预后欠佳,亟需临床关注。结核病是结核分枝杆菌感染诱发的免疫性疾病,基于对两者流行病学和免疫学机制的探索,认为结核分枝杆菌感染和自身免疫性疾病互为危险因素,在彼此疾病进展过程当中都有不可忽视的作用。本文从结核病合并自身免疫性疾病的流行病学、发病机制和临床诊治、管理等方面进行综述。     

1,25二羟基维生素D3缓解急性实验性自身免疫性:脑脊髓炎的机制

目的 探讨1,25二羟基维生素D3迅速减轻实验性自身免疫性脑脊髓炎(EAE)的机制.方法 建立Lewis大鼠急性EAE模型;预防组及治疗组分别于致敏日及症状出现日投给1,25二羟基维生素D3.致敏后第13天处死,观察中枢神经系统病理改变,TUNEL法检测凋亡细胞,免疫组化法检测iNOS、FasL及TGF-β1的表达,并测定外周血单个核细胞(MNC)培养上清液中亚硝酸盐的含量.结果 1,25二羟基维生素D3干预的预防组及治疗组与其相应对照组比较,临床评分及病理评分均降低(均P<0.01),凋亡细胞数增加(均P<0.01),半定量iNOS阳性细胞数减少,但TGF-β1、FasL阳性细胞数无明显变化.1,25二羟基维生素D3干预后,EAE大鼠外周血单个核细胞培养上清中业硝酸盐含量有增加趋势,但与对照组的差异无统计学意义.结论 1,25二羟基维生素D3通过增加炎性细胞凋亡迅速缓解EAE症状,其原因可能与改变中枢神经系统的内环境有关.     

NG及HT合并甲状腺乳头状癌的临床病理分析

目的探讨结节性甲状腺肿(nodular goiter,NG)、桥本氏甲状腺炎(Hashimoto's thyroiditis,HT)合并甲状腺乳头状癌(papillary thyroid carcinoma,PTC)的临床病理特征。方法回顾性分析270例甲状腺乳头状癌患者,筛选NG合并PTC(68例)、HT合并PTC(60例)及单纯PTC(104例)患者将其分成三组,分析其相关临床特征。结果与单纯PTC组比较,NG合并PTC患者中男性比率低、肿瘤直径小、多灶率低、双侧癌比率低、淋巴结转移率低、TGAb表达高和TPOAb表达低等,HT合并PTC患者中男性比率低、肿瘤直径小、多灶率高、双侧癌比率高、淋巴结转移率低、TGAb及TPOAb表达高等临床特征,差异均有统计学意义(均P<0.05)。结论 NG及HT合并甲状腺癌中男性患者较少,肿瘤直径小,淋巴结转移率低,HT合并PTC患者癌灶多灶率高和双侧癌比率较高。     

Rituximab in the treatment of autoimmune haematological disorders

Current treatment regimens for haematological autoimmune diseases are relatively non-selective and are often associated with considerable toxicity. Recently, it has become clear that B cells play a key role in both the development and perpetuation of autoimmunity, suggesting that B-cell depletion could be a valuable treatment approach for patients with autoimmune diseases. This article reviews data supporting the use of rituximab – an anti-CD20 monoclonal antibody that specifically depletes B cells – in four key autoimmune haematological disorders: idiopathic thrombocytopenic purpura (ITP); autoimmune haemolytic anaemia (AIHA); acquired haemophilia; and thrombotic thrombocytopenic purpura (TTP). Although treatment of ITP, AIHA, acquired haemophilia and TTP with rituximab is still relatively uncommon, results from case series and small phase II trials indicate that patients of all ages can respond to rituximab, irrespective of the number or type of prior treatments that they have received. Moreover, patients with these diseases receiving rituximab experienced predominantly mild adverse events, with only a few serious adverse events reported. These data suggest that rituximab provides an effective and well-tolerated alternative treatment option for patients with ITP, AIHA, acquired haemophilia and TTP, many of whom have limited treatment choices.     

Gene expression and pathway analysis of immune thrombocytopenic purpura

A global expression profile of peripheral blood from patients with immune thrombocytopenic purpura (ITP) was performed that identified an ITP-specific signature, which also included interferon (IFN)-induced genes. Several genes correlated with ITP have been shown to be associated with expression signatures in systemic lupus erythematosis and rheumatoid arthritis, indicating an overlap with other autoimmune disorders. Pathway analysis demonstrated that IFN signalling, death receptor and protein ubiquitination pathways were associated with ITP. These results provide the first glimpse of the genes and pathways consistently aberrant in ITP, identifying new targets for investigations of pathogenesis and treatment of ITP.