Suppression of experimental autoimmune myasthenia gravis by autologous T regulatory cells

Adoptive transfer of regulatory T (Treg) cells have been employed effectively for suppression of several animal models for autoimmune diseases. In order to employ Treg cell therapy in patients, it is necessary to generate Treg cells from the patient's own cells (autologous) that would be able to suppress effectively the disease in vivo, upon their reintroduction to the patient. Towards this objective, we report in the present study on a protocol for a successful immune-regulation of experimental autoimmune myasthenia gravis (EAMG) by ex vivo – generated autologous Treg cells. For this protocol bone marrow (BM) cells, are first cultured in the presence of GM-CSF, giving rise to a population of CD11c⁺MHCII⁺CD45RA⁺CD8^– DCs (BMDCs). Splenic CD4⁺ T cells are then co-cultured with the differentiated BM cells and expand to 90% of Foxp3⁺ Treg cells. In vitro assay exhibits a similar dose dependent manner in the suppression of T effector cells proliferation between Treg cells obtained from either healthy or sick donors. In addition, both Treg cells inhibit similarly the secretion of IFN-γ from activated splenocytes. Administration of 1 × 10⁶ ex-vivo generated Treg cells, I.V, to EAMG rats, modulates the disease following a single treatment, given 3 days or 3 weeks after disease induction. Similar disease inhibition was achieved when CD4 cells were taken from either healthy or sick donors. The disease suppression was accompanied by reduced levels of total AChR specific antibodies in the serum. Moreover, due to the polyclonality of the described Treg cell, we have examined whether this treatment approach could be also employed for the treatment of other autoimmune diseases involving Treg cells. Indeed, we demonstrated that the ex-vivo generated autologous Treg cells suppress Adjuvant Arthritis (AA) in rats.This study opens the way for the application of induced autologous Treg cell therapy for myasthenia gravis, as well as for other human autoimmune diseases involving Treg cells.     

The safety of the posterior ankle arthroscopy in management of posterior ankle impingement: A cadaveric study

BackgroundArthroscopic management of the posterior ankle impingement with the patient in supine position has the advantage of dealing with anterior ankle pathology at the same time without the need to change position of the patient. This study aims at evaluation of the safety of portal establishment and instrumentation of this technique.MethodsSixteen fresh-frozen cadaver specimens were used. The relationships of the posteromedial and posterolateral portals to the adjacent tendons and nerves and the relationship of the coaxial portal tract with the posterior ankle capsule and the flexor hallucis longus tendon were studied.ResultAngle θ₁ between the intermalleolar line and the posterior ankle coaxial portal tract averaged 1° (−10° to 22°). Angle θ₂ between the intermalleolar line and the metal rod where the neurovascular bundle started to move averaged 19° (10° to 30°). Angle θ₃ between the intermalleolar line and the metal rod where it reached the lateral border of the Achilles tendon was larger than angle θ₂ in all specimens. The angle of safety (θ_s) averaged 18° (−1° to 26°).ConclusionsInjury to the tendon, nerves or vessels is possible during establishment of the portals and resection of the os trigonum.     

妊高征肾病患者血清CysC、TGF-β1和HGF检测的临床意义

目的：探讨了妊高征肾病患者血清CysC、TGF-β1和HGF水平的变化及临床意义。方法：应用胶乳免疫增强比浊法和酶联法对38例妊高征肾病患者进行了血清CysC、TGF-β1和HGF检测,并与35名正常健康人作比较。结果：妊高征患者血清CysC、TGF-β1和HGF水平均非常显著地高于正常人组（P〈0.01）,且血清CysC水平与TGF-β1和HGF水平呈正相关（r=0.6012、0.5784,P〈0.01）。结论：检测妊高征肾病患者血清CysC、TGF-β1和HGF水平的变化对了解病情、观察疗效和预后判断均有一定的临床价值。     

振幅整合脑电图在颅内出血早产儿中应用研究

目的探讨颅内出血早产儿生后早期振幅整合脑电图(aEEG)的变化,及其早期诊断颅内出血的临床价值。方法选择2010年10月至2011年7月入住南京医科大学附属南京儿童医院新生儿医疗中心,胎龄小于37周,均经头颅B超确诊颅内出血的早产儿44例,并根据Papile分级为Ⅰ、Ⅱ、Ⅲ、Ⅳ级。生后5d内采用脑功能监护仪CFM6000描记患儿振幅整合脑电图,根据aEEG轨迹背景类型将脑电图结果分为正常aEEG波形、轻度异常aEEG波形和重度异常aEEG波形。结果 44例颅内出血早产儿中,aEEG正常14例(31.8%),轻度异常17例(38.6%),重度异常13例(29.5%)。44例患儿中,Ⅰ级颅内出血11例(25.0%),Ⅱ级颅内出血22例(50.0%),Ⅲ级颅内出血8例(18.2%),Ⅳ级颅内出血3例(6.8%)。异常aEEG预测Ⅲ、Ⅳ级颅内出血的敏感性为42.4%,特异性为100%,阳性预测值为100%,阴性预测值为36.7%。aEEG重度异常预测Ⅲ、Ⅳ级颅内出血的敏感性为87.9%,特异性为81.8%,阳性预测值为93.5%,阴性预测值为69.2%。结论对早产儿生后aEEG监测能早期预测颅内出血轻重程度。     

膜相关性鸟苷酸激酶与脑缺血

膜相关性鸟苷酸激酶（membrane associated guanylate kinase,MAGUK）是一类突触后致密蛋白（postsynaptic density,PSD）,定位于突触后膜的突触后致密区,包括PSD-95、SAP-102、PSD-93和SAP-97.MAGUK家族成员含有多个蛋白结合位点,这些特殊的结合位点负责介导多种信号的转导.MAGUK参与中枢神经系统疾病发生和发展机制,已成为神经科学研究的热点.文章简要综述了MAGUK在缺血性脑损伤中的作用.     

2012年全球上市新药

对2012年全球上市新药的基本信息，包括通用名、商品名、结构式、CAS号、研发公司、上市国家和主要适应证进行汇总，为新药研发工作者提供参考。     

Performance of EAST in diagnosing inhalant allergens in children with allergic rhinitis

The performance of enzyme linked immunosorbent assays (EAST) for identifying six indoor allergens was evaluated using skin prick test (SPT) as reference tests in 154 children with allergic rhinitis. Sensitivity of EAST ranged from 9% (cat) to 54% (HDM) with specificity of 74%(cockroach) to 100% (cat) with an agreement ranged from 58 to 86%. Cut off values ?> ?0.35 kU/L showed best sensitivity and specificity. Our findings agree with extant literature which suggests that the ability of EAST to determine the precipitating allergen is moderate. Assays for definitively identifying the inhalant allergen are currently not available.     

Successful treatment of linezolid-induced severe lactic acidosis with continuous venovenous hemodiafiltration: A case report

Linezolid is an oxazolidinone antibiotic. Linezolid-associated lactic acidosis has been reported in 6.8% of linezolid-treated patients. Lactic acidosis is associated with poor clinical outcomes, with high blood lactate levels resulting in organ dysfunction and mortality. This case report describes the development of lactic acidosis in a 64-year-old Chinese woman who had received 33 days of treatment with antituberculosis drugs and 28 days of treatment with oral linezolid for tuberculous meningitis. Severe lactic acidosis was reversed by withdrawing antituberculosis drugs and using continuous venovenous hemodiafiltration (CVVH). When the patient's condition was stable, she was transferred to the infectious disease department, and antituberculosis drugs, with the exception of linezolid, were reintroduced. This did not result in recurrence of lactic acidosis. The causal relationship between lactic acidosis and linezolid was categorized as ‘probable’ on the Adverse Drug Reaction Probability Scale. This case demonstrates that CVVH has potential as an alternative to discontinuation of linezolid alone for rapid reversal of linezolid-associated severe lactic acidosis.