Comparison of bronchial responsiveness to histamine in asthma, allergic rhinitis and allergic sensitization at the age of 7 years

BACKGROUND: Bronchial responsiveness (BR) to histamine or methacholin is a common finding in adult non-asthmatic patients with allergic rhinitis. OBJECTIVE: We tested whether BR is also present in children with a comparatively short history of allergic rhinitis in a paediatric cohort. METHODS: We performed pulmonary function tests and histamine challenges in a total of 654 children (age 7 years, participants of the German Multicenter Allergy Study) and compared PC20 FEV1 values in children with asthma, allergic rhinitis, asymptomatic allergic sensitization and non-atopic controls. RESULTS: Most pronounced BR to histamine was observed in allergic asthmatics (n = 28), irrespective of the presence or absence of allergic rhinitis. Furthermore, PC(20)FEV(1) values in non-asthmatic children with allergic rhinitis (n = 24) were not significantly different from those seen in asymptomatic atopic (n = 54) or non-atopic controls (n = 92). CONCLUSIONS: In contrast to adult study populations, 7-year-old non-asthmatic children with allergic rhinitis do not show a higher degree of BR than asymptomatic atopic or non-atopic controls. Therefore, secondary preventive measures in non-asthmatic children with allergic rhinitis (such as regular local anti-inflammatory therapy or specific immunotherapy) should be studied and applied more intensely to prevent bronchial hyper-responsiveness (BHR) and asthma in this high-risk group.     

BR提取物对小鼠S_(180)肉瘤抑制作用的研究

目的探讨BR提取物对小鼠S180肉瘤生长的抑制作用。方法将昆明种小鼠随机分为正常对照组、肿瘤对照组、试验Ⅰ组、试验Ⅱ组、试验Ⅲ组,除正常对照组外,其余4组均接种S180肉瘤肿瘤细胞悬液,正常对照组和肿瘤对照组均饮用自来水,试验Ⅰ组、试验Ⅱ组、试验Ⅲ组分别饲以4%,2%,1%的BR提取物。结果试验Ⅰ组肿瘤生长抑制率(71.81%)、生命延长率(43.24%)、小鼠体质量下降幅度明显高于试验Ⅱ组和试验Ⅲ组。结论BR提取物对小鼠S180肉瘤的生长有明显抑制作用。     

Specific forms of BAFF favor BAFF receptor-mediated epithelial cell survival

Although B cell activating factor (BAFF) and its receptor BR3 are produced and expressed by many cells, their role has been restricted to the lymphocyte lineage. Using various techniques (RT-PCR, indirect immunofluorescence, flow cytometry analysis), we observed the expression of BR3 and the production of BAFF by the human salivary gland cell line, by epithelial cells from biopsies of Sjögren's syndrome patients and their controls, but also by salivary gland epithelial cells in culture. To decipher the role of BAFF and BR3 on epithelial cells, BAFF and BR3 were neutralized by blocking antibodies or RNA specific inhibitor (siBR3) and epithelial cell survival was analyzed. Blocking BR3 promotes epithelial cell apoptosis in vitro. This apoptosis resulted in the nuclear translocation of PKCδ. BAFF neutralization by various anti-BAFF antibodies leads to different effects depending on the antibody used suggesting that only some forms of BAFF are required for epithelial cell survival. Our study demonstrates that BR3 is involved in the survival of cultured epithelial cells due to an autocrine effect of BAFF. It also suggests that epithelial cells produce different forms of BAFF and that only some of them are responsible for this effect.     

Effect of supporting substrate on the failure behavior of a polymer-infiltrated ceramic network material

Statement of problemRestorative materials are cemented on different types of substrates, such as dentin, metal, and glass-fiber posts with composite resin cores.PurposeThe purpose of this in vitro study was to evaluate the failure behavior after cycling fatigue of a polymer-infiltrated ceramic network material (PICN; VITA ENAMIC) cemented on different supporting substrates.Material and methodsPICN plates (N=80) were obtained from computer-assisted design and computer-assisted manufacturing (CAD-CAM) blocks and cemented with a resin cement to 4 different supporting substrates (n=20): (1) human dentin (PICNDen); (2) dentin analog (PICNDenAn); (3) nickel-chromium alloy (PICNNiCr); and (4) composite resin plus fiberglass post (PICNRc). For comparison, the fracture behavior of a feldspathic ceramic (FelDenAn; VITABLOCS Mark II) and an indirect composite resin (ResDenAn; Opallis LAB Resin) cemented to the DenAn substrate was investigated (n=20). Thus, specimens were composed of the restorative material layer (1-mm thick) resin cemented (0.1-mm-thick layer) to a 2-mm-thick supporting substrate. All specimens were subjected to mechanical cycling (MC) using a pneumatic cycling machine (500 000 cycles, 2 Hz, 50 N). Specimens that did not fracture during cycling were tested under compression using a universal testing machine at a cross-head speed of 0.5 mm/min until the sound of the first crack was detected using an acoustic system. Failure data were statistically evaluated using Weibull distribution. Failures were classified as radial crack, cone crack, combined, and catastrophic fracture.ResultsAll FelDenAn specimens were fractured during MC. Only 4 PICNRc specimens survived MC, so their fracture load data were not statistically analyzed. PICNNiCr showed the greatest characteristic load (L₀) value, followed by ResDenAn. Groups PICNDenAn and PICNDen showed lower and similar L₀ but statistically different Weibull modulus (m). There was a significant relationship between experimental group and failure mode (P<.001). FelDenAn and PICNRc had a higher frequency of radial cracks, whereas PICNNiCr failed from cone cracking.ConclusionsThe supporting substrate influenced the failure behavior of PICN. When the substrate had a higher elastic modulus than the restorative material, better mechanical behavior was observed.     

The lowest VE/VCO2 ratio best identifies chronic thromboembolic pulmonary hypertension

Introduction

The natural history of acute pulmonary embolism (PE) under treatment is about a gradual resolution of the thrombi, and uncommonly, the development of chronic thromboembolic pulmonary hypertension (CTEPH). We hypothesized that ventilatory efficiency parameters during cardiopulmonary exercise testing (CPET) may be able to monitor the process and predict CTEPH.

Methods

15 patients rehabilitated from acute PE (total resolution of thrombi), 44 patients with chronic PE (with residual thrombi), 66 patients with CTEPH, and 36 sedentary healthy controls performed incremental CPET.

Results

The lowest VE/VCO₂ was higher in CTEPH patients than that in chronic PE and rehabilitated patients (43.4 L/min vs 29.9 L/min vs 27.1 L/min, p < 0.005). The VE/VCO₂ slope (48.4 L/min/L/min vs 29.9 L/min/L/min vs 28.0 L/min/L/min, p < 0.005) and oxygen uptake efficiency plateau (OUEP) (37.1 L/min vs 27.0 L/min vs 25.2 L/min, p < 0.005) had the similar changes. In logistic regression analysis, the lowest VE/VCO₂ ≥ 34.35 L/min was the best predictor of CTEPH (OR 159.0, 95% CI 36.0-702.3, p < 0.001). The lowest VE/VCO₂ was higher in chronic PE patients compared with the controls (29.9 L/min vs 26.5 L/min, p < 0.05), but there was no difference between the rehabilitated patients and the controls. In multiple linear regression analysis, the percentage of vascular obstruction by ventilation-perfusion lung scanning (PVO) was the most significant independent predictor for indices of ventilatory efficiency in chronic PE and rehabilitated patients.

Conclusions

CTEPH is associated with weakened ventilatory efficiency. The lowest VE/VCO2 ratio has the best capability to predict CTEPH. Ventilatory inefficiency improves along with recovery of acute PE.     

In vivo evidence of methamphetamine induced attenuation of brain tissue oxygenation as measured by EPR oximetry

Abuse of methamphetamine (METH) is a major and significant societal problem in the US, as a number of studies have suggested that METH is associated with increased cerebrovascular events, hemorrhage or vasospasm. Although cellular and molecular mechanisms involved in METH-induced toxicity are not completely understood, changes in brain O₂ may play an important role and contribute to METH-induced neurotoxicity including dopaminergic receptor degradation. Given that O₂ is the terminal electron acceptor for many enzymes that are important in brain function, the impact of METH on brain tissue pO₂in vivo remains largely uncharacterized. This study investigated striatal tissue pO₂ changes in male C57BL/6 mice (16–20 g) following METH administration using EPR oximetry, a highly sensitive modality to measure pO₂in vivo, in situ and in real time. We demonstrate that 20 min after a single injection of METH (8 mg/kg i.v.), the striatal pO₂ was reduced to 81% of the pretreatment level and exposure to METH for 3 consecutive days further attenuated striatal pO₂ to 64%. More importantly, pO₂ did not recover fully to control levels even 24 h after administration of a single dose of METH and continual exposure to METH exacerbates the condition. We also show a reduction in cerebral blood flow associated with a decreased brain pO₂ indicating an ischemic condition. Our findings suggests that administration of METH can attenuate brain tissue pO₂, which may lead to hypoxic insult, thus a risk factor for METH-induced brain injury and the development of stroke in young adults.     

人TACI-linker-BR3双受体融合基因真核表达载体构建及其在COS-7细胞中的表达

目的:构建人双受体融合基因真核表达载体--pcDNA3.1( )-TACI-linker-BR3-IgGFc,观察其在COS-7细胞中的表达.方法:应用基因工程技术构建重组载体,脂质体转染COS-7细胞,通过Western印迹、ELISA以及免疫组化方法,检测目的蛋白的表达及其与BAFF、APRIL蛋白相互作用情况.结果:融合基因在瞬时转染的真核细胞中获得表达,并分泌至上清,转染效率能达到48%,融合蛋白能与BAFF、APRIL蛋白有效结合而且融合蛋白中分子标签IgGFc未影响双受体融合蛋白的结构及其生物学活性.结论:人TACI-linker-BR3双受体基因与IgGFc融合基因载体构建成功,表达的融合蛋白具有生物学活性,为进一步探讨SLE等自身免疫疾病的发病机制和生物学治疗方法奠定了基础.