Evaluation of allergenicity of genetically modified soybean protein extract in a murine model of oral allergen-specific sensitization

Background With the development of genetically modified crop plants there has been a growing interest in the approaches available to assess the potential allergenicity of novel gene products. For additional assessment of the potential allergenicity of expressed proteins, informative data can be generated using animal models. Soybean is one of the major source of protein in human and animal nutrition, and has also been well characterized as a major allergenic source. Advances in biotechnology have resulted in an increasing number of genetically engineered foods, and among these soybean is one of the most widespread. Objective To develop and characterize a murine model of IgE‐mediated soybean sensitization induced by intragastric immunization, in the presence of Cholera Toxin, with wild‐type soybean extract (wt‐SE) or with genetically modified soybean extract (gm‐SE). Methods Balb/c mice born in our animal facilities, from females fed on soy‐free food, were fed with the same soy‐free food and used in all the experiments. Mice were sensitized by gavages with soybean extracts, and allergen‐specific IgE and IgG responses were studied by direct ELISA and ELISA inhibition. Antigen‐specific cell proliferation and cytokine production were evaluated in spleen cell cultures. Results Sensitization with both soybean extracts induced high levels of antigen‐specific IgE and IgG1 and low levels of specific IgG2a. Both wt‐SE and gm‐SE were able to inhibit the binding of specific IgE from mice immunized with gm‐SE to the same antigen used for the ELISA coating. A comparable proliferative response was obtained with the homologous as well as with the heterologous extracts. Conclusion In sensitized mice, we observed a predominantly T‐helper type 2 (Th2)‐type immune response, with increased soybean‐specific IgE and IgG1 antibodies and a concomitant increase of IL‐4 and IL‐5 production. Results obtained by specific IgE ELISA inhibition and by antigen‐specific T cell proliferation demonstrated that wt‐SE and gm‐SE shared B and T epitopes. The present murine model of soybean sensitization established by the oral route should provide valuable information about risk assessment for food allergy from new proteins of genetically modified foods.     

Œdème cérébral aigu mortel chez un enfant diabétique

A case is reported of fatal acute cerebral oedema occurring in a 15-year-old child suffering diabetic ketoacidosis. He had severe gastro-enteritis, with a weight lose of 8 kg over a period of 8 days (initial weight = 50 kg). He was admitted in a stupor with pH 7.15, 129 mmol.l-1 natraemia, and 31 mmol.l-1 blood glucose concentration. Blood osmolaity was calculated to be 310 mosmol.l-1. He was rehydrated with 416 ml.h-1 normal saline and 416 ml.h-1 of 1.4% sodium bicarbonate. At the same time a total dose of 75 i.u. of ordinary insulin was given. After 2 h, the patient's condition suddenly worsened with unreactive coma, bilateral fixed mydriasis, respiratory pauses, and impairment of haemodynamic state (heart rate 150 b.min-1, blood pressure 80/50 mmHg). The diagnosis of cerebral oedema with severe intracranial hypertension was confirmed by different investigations. Despite ventilatory support and continued intensive care, the patient died a few hours later. It is concluded that some degree of subclinical brain swelling could be common occurrence during diabetic ketoacidosis, present maybe even before the start of treatment. Such cases of cerebral oedema are often reported, but the pathophysiological mechanisms remain unclear. However, unlike this case, rehydration must be moderate (less than 41.m-2.day-1), especially in case of hyponatraemia. Insulin and sodium bicarbonate must be used with care. Early rigorous clinical and biological monitoring is essential. Treatment should aim at a progressive correction of the metabolic disturbances.     

高压氧治疗对脑梗死患者血清基质金属蛋白酶-9的影响

目的探讨高压氧（HBO）治疗后急性脑梗死患者血清基质金属蛋白酶-9（MMP-9）水平的动态变化及其与临床疗效的关系。方法选取首次发病的24h以内的颈内动脉系统急性脑梗死患者76例，分为高压氧治疗组（HBO组，36例）和常规治疗组（常规组，40例）。常规组仅给予常规治疗，HBO组在常规治疗基础上加用HBO治疗。30例年龄、性别与脑梗死患者相匹配的健康人为健康对照组（正常对照组）。采用酶联免疫吸附双抗体夹心法测定脑梗死患者入院时、发病后第3、5、10天以及正常对照组血清MMP-9。所有患者于入院时和治疗后10d、1个月进行神经功能缺损评分，评价HBO组和常规组之间的疗效差异。结果（1）与正常对照组比较，HBO组和常规组入院时血清MMP-9的浓度均明显增高，差异有统计学意义（P〈0.01），但后二者之间差异无统计学意义（P〉0.05）。与治疗前相比，常规组和HBO组血清MMP-9水平均呈现先增高后降低的动态变化趋势，3d时达高峰，在治疗后3、5d时HBO组血清MMP-9浓度低于同期常规组（P〈0．05）。（2）治疗1个月后，神经功能缺失评分HBO组明显低于常规组；HBO组疗效优于常规组（P〈0．05）。（3）脑梗死患者神经功能缺损评分减少值与患者发病后第3天之血清MMP-9水平呈显著负相关。结论HBO治疗能降低脑梗死患者升高的血清MMP-9浓度，减轻神经功能缺失程度，其临床疗效可能与降低患者血清MMP-9的浓度有关。     

Deep brain stimulation for Parkinson''s disease: electropermeabilization and activation

Deep brain stimulation, DBS, is an accepted technique for the treatment of Parkinson's disease. DBS affects the electrical functions of neurons, but exactly how it alters those functions is not clearly explained. An electrical model is determined to simulate treatment with DBS of the sub thalamic nucleus. This model shows the difference in electrical fields between the inside and the outside the neurons. The generated electrical field near the electrodes is high enough to perform an electropermeabilization of the cell membranes, which most likely blockade normal nerve pulses or reduce the nerve impulse speed. Further away from the electrodes activation of large axons is performed.     

2型糖尿病患者血清CA19-9水平分析

目的 分析2型糖尿病患者血清CA19-9水平.方法 测定60例2型糖尿病患者和60例健康人血清CA19-9浓度,进行对比分析.结果 在控制了年龄、性别、空腹血糖和HbAlc之后,CA19-9水平与2型糖尿病存在显著相关关系.结论 我们建议在区分糖尿病患者良恶性胰腺肿瘤时应该采用更高的参考值.     

缺氧缺血性脑损伤大鼠Caspase-9的表达及高压氧干预疗效

目的:探讨高压氧(HBO)对缺氧缺血新生大鼠模型神经细胞凋亡的影响,以及Caspase-9在该过程中的作用。方法:建立缺氧缺血(HIBD)大鼠模型,观察HBO对缺氧缺血性脑损伤的改善情况,并用免疫组化的方法检测Caspase-9表达在缺氧缺血脑组织中的动态变化。结果:HIBD模型组大鼠造模后18h、24h、48h、96h不同时间段患侧海马区及皮层区Caspase-9活性蛋白的表达均明显高于假手术组(P值均<0.05);HBO干预组大鼠海马区和皮层区各相应时间点Caspase-9活性蛋白表达均低于HIBD模型组大鼠(P值均<0.05),部分时间点接近假手术组基线水平。结论:HBO可以减轻新生大鼠HIBD模型神经细胞的凋亡;不同时程HBO干预治疗可降低HIBD模型大鼠皮层、海马神经细胞Caspase-9的表达活性。     

Common human Toll-like receptor 9 polymorphisms and haplotypes: association with atopy and functional relevance

BACKGROUND: Toll-like receptor 9 (TLR9) is a pattern-recognition receptor that detects unmethylated CpG motifs prevalent in bacterial and viral DNA. TLR9 stimulation is a key event after bacterial infection, triggering innate immunity and T-helper type 1 skewed adaptive immunity. Synthetic CpG-oligodeoxynucleotides (CpG-ODNs) represent a promising and novel class of immune adjuvants for allergy treatment, vaccination, and cancer therapy. However, common functional TLR9 gene variants could interfere with the clinical utilization of CpG-ODN in immunotherapy. Recently, a possible association of TLR9 polymorphism C-1237T with asthma has been reported. OBJECTIVE: The aim of the present study was to investigate whether TLR9 polymorphisms or haplotypes have functional relevance and are associated with atopy. METHODS: We genotyped five common TLR9 single-nucleotide polymorphisms (SNPs) in promoter, exon, and intron regions of the gene in 527 healthy blood donors, and estimated four common haplotypes. The total IgE and specific IgE levels against the most common aeroallergens were measured (n=303). IFN-alpha production by plasmacytoid dendritic cells (pDCs) was analysed after stimulation with TLR9 ligand CpG-ODN (n=220). RESULTS: No significant influence of common TLR9 polymorphisms and haplotypes on the total and specific IgE levels was found. Functional analysis of CpG-ODN-induced IFN-alpha did not indicate a significant role for common TLR9 gene polymorphisms in TLR9 function. CONCLUSION: We conclude that common genetic differences in the TLR9 gene exert no major influence on allergy susceptibility, and are unlikely to have on impact on clinical application of CpG-ODNs.     

MRP1/CD9蛋白在人肝细胞癌中的表达及其意义

目的　探讨MRP1 /CD9蛋白在人肝细胞癌 (HCC)中的表达及其与癌侵袭转移的关系。方法　构建肝癌组织芯片。样本包括肝细胞癌及癌旁肝组织 1 5 2例,癌栓 2 2例,肝内转移癌 4例,肝外转移癌 1 7例。正常对照肝组织 5例。应用免疫组织化学 (免疫组化 )方法检测肝癌组织芯片中样本MRP1 /CD9蛋白的表达。结果　 2 7% ( 4 1 /1 5 2 )肝细胞癌原发灶表达MRP1 /CD9蛋白。伴癌栓形成HCC中MRP1 /CD9蛋白表达率低于无癌栓形成者 (分别为 2 1. 8 2%和 4 0. 4 8% ; P < 0. 0 5 )。巨块型肝癌中MRP1 /CD9 蛋白表达率亦低于直径在 1 0cm以下者 (分别为 5%和 3 4. 8 2% ; P <0. 01 )。MRP1 /CD9蛋白表达尚与HCC病理分级及血清AFP水平有关:病理分级 2级的阳性表达率高于 3 ~ 4级 (分别为 3 9. 0 2%和 2 2. 5 2% ; P = 0. 0 4 3 ),血清AFP≤ 2 0μg/L者阳性表达率高于 >2 0μg/L者 (分别为 4 1. 9 4%和 2 2. 5 0% ; P = 0. 0 2 9 )。结论　肝细胞癌MRP1 /CD9蛋白表达水平低下可能与癌组织侵袭转移有关。     

大学生篮球运动员集训期间部分淋巴细胞亚群和Th1/Th2细胞因子mRNA表达变化分析

目的:探讨大负荷体能训练对大学生篮球运动员细胞免疫功能的影响。方法:14名男子大学生篮球运动员进行为期16周的集训,在训练期间分次对运动员外周血淋巴细胞亚群(CD3+、CD4+/CD8+淋巴细胞比值、NK细胞比例)和Th1/Th2细胞因子 mRNA表达进行检测。结果:在两次分别持续了6周的训练期后,运动员外周血CD3+淋巴细胞数于增加后出现显著下降,从第7周的峰值(59.74±7.18)下降至第16周的最低值(52.02±7.92)(P<0.001);CD8+细胞数第16周(31.15±6.25)与第3周(37.98±7.05)相比显著下降(P<0.05);NK细胞数从第7周的最高值(19.62±5.21)下降至第14周的最低值(14.41±7.93)(P<0.05);IL-4 mRNA表达训练后与基础值(6.56±0.71)相比显著增加,从第7周的7.04±0.35和第14周的7.30±0.25,直至第16周达到最大值7.36±0.45(P<0.05),其他指标的变化不具有统计学意义。结果提示,大负荷训练使运动员细胞免疫功能削弱,Th1/Th2平衡向Th2方向漂移。