地塞米松抑制哮喘小鼠肺RANTES的表达

目的 研究地塞米松对哮喘小鼠调节激活正常T细胞表达和分泌细胞因子(RANTES)蛋白和mRNA表达的影响.方法 将30只雌性BALB/c小鼠随机分为3组(每组10只):对照组、哮喘组、激素干预组,收集支气管肺泡灌洗液(BALF),行白细胞和嗜酸粒细胞(EOS)计数;酶联免疫吸附法(ELISA)测定BALF和血清中RANTES含量;肺组织切片HE染色,光镜下计数细胞总数和EOS百分比;部分行免疫组化染色检测肺组织RANTES蛋白;用原位杂交法检测肺组织RANTES mRNA表达.结果 哮喘组白细胞总数、EOS百分比、RANTES浓度明显升高(P＜0.01),干预组明显低于哮喘组(P＜0.01);哮喘组肺组织RANTES蛋白及mRNA表达显著高于对照组(P＜0.01),主要表达于上皮细胞;干预组肺组织RANTES蛋白及mRNA表达显著低于哮喘组(P＜0.01).结论 地塞米松可抑制RANTES表达和活性而发挥抗EOS炎症作用,这可能是其控制哮喘发病的重要机制之一.     

Influence of dosing frequency and schedule on the response of chronic asthmatics to the aerosol steroid,budesonide

The influence of various dosing regimens on the response of asthmatic patients to aerosol steroid was investigated. Budesonide, a topically active corticosteroid like beclomethasone dipropionate, was given q.i.d. or b.i.d., in the morning or A.M./P.M., at doses of 400, 800, and 1600 μg/day. Each patient (n = 34) took every treatment combination for 2 wk. The antiasthmatic and systemic effects, measured by changes in peak expiratory flow rate (PEFR), blood eosinophils, and serum cortisol levels increased approximately linearly on log dose budesonide (p < 0.0005). Systemic effects of the drug were nonsignificant at low dosage. At high dosage, morning dosing conserved hypothalamic-pituitary-adrenal function, but at the cost of a marginal reduction in efficacy (Δ PEFR, p =0.12). Halving the dose frequency reduced the antiasthmatic potency of the drug, i.e., PEFR fell by an amount equivalent to approximately eightfold reduction in daily dosage (p = 0.002). This effect was not evident when asthma was in remission but became so with asthma in relapse. Overall, the q.i.d. A.M./P.M. regimen showed the best risk-benefit relationships. The data indicate (I) that reductions in dose frequency made with the hope of improving patient compliance and thus conserving the drug's long-term efficacy are likely to lead to the reverse effect, (2) that the clinician can conserve a better balance of risk vs benefit by titrating dosage in terms of puffs per dose rather than doses per day, and (3) that patients can increase the antiasthmatic efficacy of this aerosol steroid without any increase in drug costs (or apparent risk) by simply increasing dosing frequency. These therapeutic considerations probably apply to some or all of the other topically active steroids currently used to treat asthma.     

Application of PC-SAFT EOS for Pharmaceuticals: Solubility,Co-Crystal,and Thermodynamic Modeling

In this study, the applicability of the perturbed chain statistical associating fluid theory (PC-SAFT) was evaluated for pharmaceutical compounds. For this purpose, the parameters of the PC-SAFT equation of state (EOS) were regressed by applying the experimental solubility data of 54 pharmaceuticals in pure solvents. The reported errors for train and test data show the suitability of the PC-SAFT EOS. The applicability of the PC-SAFT EOS was explored by its prediction accuracy for the ternary system of medicine in solvent mixtures. The model errors were 23 and 26% for two ternary systems of salicylic acid and lidocaine HCl in solvent mixtures of ethanol and water, respectively. The co-crystal formation of salicylic acid-sulfamethazine in methanol was investigated by the PC-SAFT EOS. Finally, the reaction and crystallization sections for acetaminophen production from p-aminophenol were simulated by accompanying the PC-SAFT EOS and equilibrium assumption. The purification efficiencies for acetaminophen were obtained to be 93–98% for different temperatures.     

Measurement of Trabecular Bone Score of the Spine by Low-Dose Imaging System (EOS®): A Feasibility Study

Purpose/Introduction: Measurement of trabecular bone score (TBS^®) of the lumbar spine on dual energy X-ray absorptiometry (DXA) devices improves fracture risk prediction. We conducted a proof of concept study to assess the feasibility of TBS^® measured on the low-dose imaging system EOS^®. Methods: TBS was assessed on both DXA and EOS^® in 122 patients aged ≥ 50 yr, receiving no anti-osteoporotic treatment. The TBS^® was computed on full-body EOS^® images, focusing on the lumbar spine region. The patients were also scanned with a DXA bone densitometer (Hologic) and the spine and hip bone mineral density (g/cm²) were computed. Results: TBS^® measurement on EOS^® was not possible in 34 patients due to technical problems. It could be measured on both DXA and EOS^® in 88 patients (28 with severe low-trauma fracture and 60 without fracture). TBS-EOS values were significantly lower in fractured patients compared to nonfractured patients. TBS-EOS was associated with the presence of fractures as reported by an AUC of 0.70. Odds ratio of TBS-EOS for the presence of severe low-trauma fracture was 2.00 [1.24–3.25], p?=?0.005. Conclusions: This proof of concept study, based on a prototype version of the TBS-EOS, demonstrated the feasibility of the measurement of TBS^® on low-dose EOS^® imaging devices. Results show that the TBS-EOS was lower in patients with severe low-trauma fractures compared to nonfractured patients independently from bone mineral density. Some technical issues need to be solved before its eventual use in routine clinical settings. Additional prospective studies are still needed to define the actual contribution of this new technique.     

平喘合剂对哮喘患儿EOS及sICAM-1的影响及机理探讨

目的:观察平喘合剂对哮喘患儿外周血嗜酸性粒细胞(EOS)计数、血清可溶性细胞间粘附分子(sICAM一1)水平的影响,探讨其作用机制.方法:将120例哮喘患儿随机分为治疗组60例、中药对照组30例、西药对照组30例.治疗组予口服自制平喘合剂,中药对照组予口服京制咳嗽痰喘丸,西药对照组予硫酸特布他林(商品名:博利康尼).7...     

Dysconnectivity in schizophrenia: where are we now?

The disconnection hypothesis suggests that the core symptoms of schizophrenia (SZ) are related to aberrant, or ‘dys-’, connectivity between distinct brain regions. A proliferation of functional and structural neuroimaging studies have been conducted to investigate this hypothesis, across the full course of the disorder; from people at Ultra-High-Risk of developing psychosis to patients with chronic SZ. However the results of these studies have not always been consistent, and to date, there have been no attempts to summarise the results of both methodologies in conjunction. In this article, we systematically review both the structural and functional connectivity literature in SZ. The main trends to emerge are that schizophrenia is associated with connectivity reductions, as opposed to increases, relative to healthy controls, and that this is particularly evident in the connections involving the frontal lobe. These two trends appear to apply across all stages of the disorder, and to be independent of the neuroimaging methodology employed. We discuss the potential implications of these trends, and identify possible future investigative directions.     

Three-dimensional reconstructions for asymptomatic and cerebral palsy children's lower limbs using a biplanar X-ray system: A feasibility study

The aim of this study is to explore the feasibility of 3D subject-specific skeletal reconstructions of lower limb in children using stereoradiography, and to assess uncertainty of clinical and anatomical parameters for children with cerebral palsy and for healthy children. The stereoradiography technique, using the EOS^® system (Eos-imaging^®), is based on the acquisition of two simultaneous digital anteroposterior and lateral X-rays, from head to feet in standing position and at low radiation dose. This technique allows subject-specific skeletal 3D reconstructions. Five children with cerebral palsy (CP) and 5 typically developing children (TD) were included in the study. Two operators performed the lower limb reconstructions twice. Tridimensional reconstructions were feasible for children over the age of 5 years. The study of reproducibility of anatomical parameters defining skeletal alignment showed uncertainties under 3° for the neck shaft angle, the femoral mechanical angle, and for the femoral and tibial torsions. The maximum degree of uncertainty was obtained for the femoral tibial rotation (4° for healthy children and 3.5° for children with CP).     

血清sIgE、总IgE、EOS与慢性鼻-鼻窦炎伴鼻息肉发生的相关性分析

目的：探讨血清sIgE、总IgE浓度梯度、嗜酸粒细胞（EOS）与慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）发生的危险因素以及临床指标的筛选。方法：将152例慢性鼻-鼻窦炎患者分为慢性鼻-鼻窦炎不伴鼻息肉（CRSs—NP）组和CRSwNP组,行体外20种过敏原筛查,测定血清sIgE、总IgE、EOS百分比。结果：①CRSsNP患者血清总IgE浓度主要集中在1级,而CRSwNP患者血清总IgE浓度主要集中在2、3级（Z=0．906,P〉0．05）。分别比较两组患者血清sIgE分级．差异无统计学意义（P〉0．05）。②CRSwNP患者EOS百分比明显高于CRSsNP患者（F=4．337,P=0．039;t=3．315,P〈0．01）。且CRSwNP患者E0s百分比95％可信区间为3．90％～5．26％,5％TM值为4．3％,高于CRSsNP组及正常值。CRSwNP组患者EOS百分比,按sIgE值分梯度（分级）后,CRSwNP各组（级）之间比较差异均无统计学意义（P〉0．05）。③CRSwNP患者变应原多为混合型变应原,并且随着变应原浓度梯度的升高,混合型变应原过敏的CRSwNP组患者比例高于CRSsNP患者（χ2=8．595,P〈20．05）。结论：CRSwNP的发牛与EOS、混合变应原的存存有关。且当EOS百分比在3．90％～5．26％范围内CRSwNP更易发生。而血清总IgE、sIgE浓度不能单独作为CRswNP的发生因素。利用过敏原筛查结果结合临床症状,能更早地了解并远离过敏原,利于慢性鼻鼻窦炎围手术期治疗方案的制定。     

通窍止鼽汤对变应，陡鼻炎SD大鼠的EOS、IgE和组胺的影响

目的：研究通窍止鼽汤对变应性鼻炎sD大鼠鼻黏膜及外周血中EOS数量、血清IgE和组胺含量的影响,探讨其治疗变应性鼻炎的作用机制。方法：选取成年SD大鼠60只,随机分为空白纽、模型组、对照纽和通窍止鼽汤低、中、高剂量组共6组,每组10只。采用卵清蛋白和热灭活百日咳杆菌为致敏原,对大鼠进行实验性变应性鼻炎造模。造模成功后,空白组和模型组灌服生理盐水2mL／只;对照组灌服辛芩颗粒6g／kg;通窍止鼽汤低、中、高剂量组分别灌服中药液8．75g／kg、17．5g／kg、35g／kg;以上用药均1次／d,共14d。测定大鼠鼻黏膜和外血中EOS数量、血清IgE水平和组胺含量。结果：通窍止鼽汤各剂量组和对照组均能减少EOS数量;降低血清IgE水平和组胺含量,以高剂量组效果最佳。结论：通窍止鼽汤能有效抑制EOS活化,减少IgE合成与组胺释放,减轻鼻黏膜炎症浸润,从而达到治疗变应性鼻炎的目的。