BACKGROUND & AIMS: :Toluene diisocyanate (TDI) and 4,4'-methylenediphenyl diisocyanate (MDI), used in the production of polyurethane foam, are well known for their irritating and sensitizing properties. Contradictory results have been obtained on their genotoxicity. We investigated the genotoxicity and protein binding of inhaled TDI and MDI in mice by examining micronucleated polychromatic erythrocytes (PCEs) in bone marrow and peripheral blood and TDI- and MDI-derived adducts in hemoglobin. Male C57Bl/6J mice (8 per group) were exposed head-only to TDI vapour (mean concentrations 1.1, 1.5, and 2.4mg/m(3); the mixture of isomers contained, on the average, 63% 2,4-TDI and 37% 2,6-TDI) or MDI aerosol (mean concentrations 10.7, 20.9 and 23.3mg/m(3)), during 1h/day for 5 consecutive days. Bone marrow and peripheral blood were collected 24h after the last exposure. Inhalation of TDI caused sensory irritation (SI) in the upper respiratory tract, and cumulative effects were observed at the highest exposure level. Inhalation of MDI produced SI and airflow limitation, and influx of inflammatory cells into the lungs. Hemoglobin adducts detected in the exposed mice resulted from direct binding to globin of 2,4- and 2,6-TDI and MDI, and dose-dependent increases were observed especially for 2,4-TDI-derived adducts. Adducts originating from the diamines of TDI (toluene diamine) or MDI (methylene dianiline) were not observed. No significant increase in the frequency of micronucleated PCEs was detected in the bone marrow or peripheral blood of the mice exposed to TDI or MDI. The ratio of PCEs and normochromatic erythrocytes (NCEs) was reduced at the highest concentration of MDI, and a slight reduction of the PCE/NCE ratio, dependent on cumulative inhaled dose, was also seen with TDI. Our results indicate that inhalation of TDI or MDI (1h/day for 5 days), at levels that induce toxic effects and formation of TDI- or MDI-specific adducts in hemoglobin, does not have detectable genotoxic effects in mice, as studied with the micronucleus assay.

背景与目标： 用于生产聚氨酯泡沫的甲苯二异氰酸酯 (TDI) 和4,4 '-亚甲基二苯基二异氰酸酯 (MDI) 因其刺激性和敏化性能而众所周知。在其遗传毒性方面获得了矛盾的结果。我们通过检查骨髓和外周血中的微核多色红细胞 (PCEs) 以及血红蛋白中TDI和MDI衍生的加合物，研究了小鼠吸入TDI和MDI的遗传毒性和蛋白质结合。雄性C57Bl/6J小鼠 (每组8只) 仅头部暴露于TDI蒸气 (平均浓度1.1、1.5和2.4 mg/m(3); 异构体混合物平均含有63% 2,4-TDI和37% 2,6-TDI) 或MDI气溶胶 (平均浓度10.7，20.9和23.3 mg/m(3))，在1h/天内连续5天。在最后一次暴露后24小时收集骨髓和外周血。吸入TDI会引起上呼吸道的感觉刺激 (SI)，并且在最高暴露水平下观察到累积效应。吸入MDI会导致SI和气流受限，并使炎症细胞流入肺部。在暴露的小鼠中检测到的血红蛋白加合物是由与2,4-和2,6-tdi和MDI的珠蛋白直接结合引起的，并且观察到剂量依赖性增加，特别是对于2,4-tdi衍生的加合物。未观察到源自TDI (甲苯二胺) 或MDI (亚甲基二胺) 的二胺的加合物。在暴露于TDI或MDI的小鼠的骨髓或外周血中未检测到微核pce的频率显着增加。在最高浓度的MDI下，PCE和常染红细胞 (NCEs) 的比率降低，并且TDI还观察到PCE/NCE的比率略有降低，这取决于累积吸入剂量。我们的结果表明，吸入TDI或MDI (1小时/天，持续5天)，其水平可诱导毒性作用并在血红蛋白中形成TDI或MDI特异性加合物，在小鼠中没有可检测到的遗传毒性作用，用微核测定法进行研究。

BACKGROUND & AIMS: BACKGROUND:The immunopathological mechanism for occupational asthma induced by toluene diisocyanate (TDI) remains to be further clarified. There have been few reports suggesting involvement of neutrophils in inducing bronchoconstriction after TDI inhalation. OBJECTIVES:To further understand the role of neutrophils in the pathogenesis of TDI-induced asthma. MATERIALS AND METHODS:Eight TDI-induced asthmatic subjects were classified as group I, and five exposed workers who had complained of work-related symptoms and worked in the same workplace, but showed negative bronchial challenges were enrolled as controls (group II). Serum neutrophil chemotactic activity during TDI bronchial challenge test was measured by the Boyden chamber method. Induced sputum was collected before and after the TDI bronchial challenge test. The myeloperoxidase (MPO) and interleukin (IL) -8 levels in the sputum were measured using RIA and ELISA. RESULT:Serum neutrophil chemotactic activity significantly increased at 10 min (P = 0.01), then decreased at 60 min (P = 0.02) and remained unchanged for up to 420 min (P = 0.07) in group I subjects, while no significant changes were found in group II subjects (P > 0.05). MPO and IL-8 were abundantly present in the sputum of all the TDI-induced asthmatic subjects and they increased significantly at 420 min after the bronchial challenges (P = 0.02, P = 0.03, respectively), while no significant changes were noted in group II subjects (P > 0.05). CONCLUSION:These findings support the view that activated neutrophils may contribute to bronchoconstriction induced by TDI which may be associated with IL-8 release.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:An appreciable number of patients with toluene diisocyanate (TDI)-induced asthma have high serum levels of specific IgE (sIgE) antibody to TDI-human serum albumin conjugate (HSA). A recent investigation suggested a role of specific IgG (sIgG) in the development of TDI asthma. METHODS:We observed the changes in the levels of specific IgE and IgG antibodies to TDIHSA conjugate in TDI-induced asthmatic patients during seven years avoidance. RESULTS:Six subjects with high sIgE and five with high sIgG were enrolled. All of them had taken anti-asthmatic medications with complete avoidance. Serum levels of sIgE and sIgG to TDI-HSA conjugate were detected by ELISA. The level of sIgE continued to decline up to 7 years and the mean half-life was 3.9 years. The mean half-life of sIgG was 4.5 yrs. CONCLUSION:These findings suggest that both sIgE and sIgG to TDI-HSA conjugate may persist for several years after the last exposure to TDI.

背景与目标：

BACKGROUND & AIMS: :Tissue Doppler imaging (TDI) was investigated for its applicability for detecting cardiac function and early cardiotoxicity in breast cancer patients treated with anthracyclines. A total of 40 women (age range 18 to 65 years) were enrolled, who had not received anthracyclines previously and had normal systolic and diastolic cardiac function. All healthy patients in the control group were of the same age. Each patient underwent not only standard echocardiographic measurements (ventricular dimensions and wall thickness, ejection fraction, E-wave deceleration time (DT), E/A ratio), but also specific imagings (E-septum separation, pulmonary venous flow), and in addition the myocardial velocity of many segments of mitral anulus obtained with pulsed wave tissue Doppler imaging were performed during the one year of observation period. Based on the results we found that systolic left ventricular function did not change significantly - neither in the study nor in the control group. Diastolic left ventricular function was impaired in 39 patients (97.5%), and 30 (75%) of these showed clear changes by means of both the traditional E/A ratio and TDI. Diastolic dysfunction in 9 patients (22.5%), however, could be detected only with TDI. The analysis of myocardial velocity in different segments showed that diastolic dysfunction does not develop in a homogeneous way but in a different way in segments. Diastolic function was intact in the control group during the study. The detectable myocardial damage occurred in the study group of young female patients without risk factors as a result of one year anthracycline therapy was so severe that the possible outcome might be serious congestive heart failure or death. Our results confirmed our assumptions that TDI is a more precise and useful examination method than traditional ones (E/A ratio or deceleration time) to demonstrate isolated diastolic dysfunction as a result of chemotherapy. Relevant extra information might be given by TDI compared to parameters describing diastolic functions depending on several changing values. TDI may become a regularly and more widely used noninvasive method to detect subclinical cardiotoxicity emerging after chemotherapy.

背景与目标： : 研究了组织多普勒成像 (TDI) 在检测蒽环类药物治疗的乳腺癌患者的心脏功能和早期心脏毒性中的适用性。共有40名女性 (年龄在18至65岁之间) 被纳入，她们以前没有接受过蒽环类药物，并且具有正常的收缩和舒张功能。对照组中所有健康患者的年龄相同。每位患者不仅接受了标准的超声心动图测量 (心室尺寸和壁厚，射血分数，E-波减速时间 (DT)，E/A比)，而且还接受了特定的成像 (E-隔膜分离，肺静脉血流)，此外，在一年的观察期内，还通过脉冲波组织多普勒成像获得了二尖瓣环的许多段的心肌速度。根据研究结果，我们发现左心室收缩功能没有显着变化-无论是在研究还是在对照组中。39例患者 (97.5% 例) 的左心室舒张功能受损，其中30例 (75% 例) 通过传统的E/A比和TDI显示出明显的变化。然而，只有TDI才能检测到9例患者 (22.5%) 的舒张功能障碍。对不同节段心肌速度的分析表明，舒张功能障碍不是以均匀的方式发展，而是以不同的方式发展。在研究期间，对照组的舒张功能完好无损。在没有危险因素的年轻女性患者中，由于接受了一年的蒽环类药物治疗，可检测到的心肌损害非常严重，可能的结果可能是严重的充血性心力衰竭或死亡。我们的结果证实了我们的假设，即TDI是一种比传统方法 (E/a比或减速时间) 更精确，更有用的检查方法，可以证明化疗导致的孤立舒张功能障碍。与描述舒张功能的参数相比，TDI可能会提供相关的额外信息，具体取决于几个变化的值。TDI可能成为一种定期且更广泛使用的无创方法，用于检测化疗后出现的亚临床心脏毒性。

BACKGROUND & AIMS: :One of the many commercial technologies for genotyping single nucleotide polymorphisms (SNPs) is template direct dye-terminator incorporation with fluorescence-polarization (TDI-FP assay). It is a single-base extension assay followed by reading the fluorescence polarization values in an appropriate instrument. We have evaluated the suitability of the TDI-FP technique to detect haploid uniparentally inherited DNA polymorphisms on the nonrecombining portion of the Y chromosome. A sample of 47 individuals has been genotyped for 8 Y chromosome biallelic markers. The SNP typing was blindly duplicated by the denaturing high-performance liquid chromatography (DHPLC) technique for comparison. In the cases under examination the TDI-FP assay was able to resolve an allelic state fully. Such a result showed 100% concordance indicating how efficiently the TDI assay can be used to genotype Y chromosome DNA SNPs. However, a percentage of indeterminate genotypes remained unresolved by simple visual inspection: it varied from 0% to 11% depending on the SNP locus and on the success of amplification. This is consistent with previous findings. A maximum likelihood classificatory analysis allowed some of the indeterminate genotypes to be assigned and some potentially misclassified samples to be identified. Their percentage remains relatively high despite retyping and therefore alternative techniques for these noncompliant situations are required.

背景与目标： : 用于单核苷酸多态性 (snp) 基因分型的许多商业技术之一是模板直接染料-终止剂与荧光偏振结合 (tdi-fp测定)。这是一种单碱基延伸测定法，然后在适当的仪器中读取荧光偏振值。我们已经评估了tdi-fp技术在Y染色体非重组部分上检测单倍体单亲遗传DNA多态性的适用性。已对47个个体的样本进行了8个Y染色体双等位基因标记的基因分型。通过变性高效液相色谱 (DHPLC) 技术盲目复制SNP分型，以进行比较。在接受检查的情况下，tdi-fp测定能够完全解析等位基因状态。这样的结果显示出100% 一致性，表明TDI测定可有效地用于基因型Y染色体DNA snp。然而，通过简单的目视检查，不确定基因型的百分比仍未解决: 取决于SNP基因座和扩增的成功程度，从0% 到11% 不等。这与以前的发现是一致的。最大似然分类分析允许分配一些不确定的基因型，并识别一些可能错误分类的样本。尽管重新键入，但它们的百分比仍然相对较高，因此需要针对这些不合规情况的替代技术。

BACKGROUND & AIMS: :We estimate trends and geographical differences in the heroin epidemic in the European Union plus Croatia and Turkey by analyzing aggregated data on first heroin treatment admissions (cases) during 2000-2009. In 2005-2009 the proportion of drug injectors was higher in Central and Eastern European countries (CEECs) than in Western European countries (WECs), whereas the opposite occurred with mean age at first heroin use and first treatment. During this period, the number of cases, cases per center, and proportion of injectors in WECs declined, whereas mean age at first treatment and first heroin use increased. The opposite occurred in Turkey, except for proportion of injectors, while trends were less clear in the other CEECs. In the 7 WECs with data, trends in 2000-2005 and 2005-2009 were similar. This suggests that the number of recent-onset heroin users and heroin injectors may have declined some years before the study period, especially in WECs.

背景与目标： : 我们通过分析2000-2009年首次海洛因治疗入院 (病例) 的汇总数据，估计了欧盟以及克罗地亚和土耳其海洛因流行的趋势和地理差异。在2005-2009年，中欧和东欧国家 (ceec) 的吸毒者比例高于西欧国家 (WECs)，而首次使用海洛因和首次治疗的平均年龄则相反。在此期间，WECs的病例数，每个中心的病例数以及注射器的比例有所下降，而首次治疗和首次使用海洛因的平均年龄却有所增加。相反的情况发生在土耳其，除了注射器的比例，而其他ceec的趋势不太清楚。在有数据的7个wec中，2000-2005和2005-2009的趋势相似。这表明，在研究期之前的几年中，最近发作的海洛因使用者和海洛因注射器的数量可能已经下降，尤其是在wec中。

BACKGROUND & AIMS: :Isocyanate-induced asthma, the most commonly reported cause of occupational asthma, has been difficult to diagnose and control, in part, because the biological mechanisms responsible for the disease and the determinants of exposure have been difficult to define. Appropriate animals models of isocyanate asthma will be instrumental to further our understanding of this disease. Previous studies have demonstrated that dermal exposure to isocyanates in mice results in systemic sensitization that leads to eosinophilic airways inflammation upon subsequent airway challenge. We hypothesized that inhalation of vapor phase toluene diisocyante (TDI) will lead to immunologic sensitization in mice and that subsequent challenge will induce pathology and immune system alterations indicative of asthma found in humans. To determine the impact of exposure dose as well as the involvement of immune (allergic) or nonimmune mechanisms, a murine model of TDI asthma was established and characterized following either low-level subchronic or high-dose acute inhalation TDI exposure. C57BL/6 J mice were exposed to TDI by inhalation either subchronically for 6 weeks (20 ppb, 4 h/day, 5 days/week) or by a 2-h acute exposure at 500 ppb. Both groups were challenged 14 days later via inhalation with 20 ppb TDI for 1 h. Mice that underwent the subchronic exposure regimen demonstrated a marked allergic response evidenced by increases in airway inflammation, eosinophilia, goblet cell metaplasia, epithelial cell alterations, airway hyperreponsiveness (AHR), T(H)1/T(H)2 cytokine expression in the lung, elevated levels of serum IgE, and TDI-specific IgG antibodies, as well as the ability to transfer these pathologies to naive mice with lymphocytes or sera from TDI exposed mice. In contrast, mice that received acute TDI exposure demonstrated increased AHR, specific IgG antibodies, and pathology in the lung consistent with asthma, but without the presence of elevated serum IgE, lung eosionophilia, or increased expression of T(H) cytokines. These results describe mouse models for TDI asthma consistent with that found in workers with occupational asthma and indicate that the pulmonary pathology associated with TDI can vary depending upon the exposure paradigm.

背景与目标： 异氰酸酯引起的哮喘是职业性哮喘的最常见原因，很难诊断和控制，部分原因是难以确定导致该疾病的生物学机制和暴露的决定因素。适当的异氰酸酯哮喘动物模型将有助于我们进一步了解这种疾病。先前的研究表明，小鼠的皮肤暴露于异氰酸酯会导致全身性致敏，从而在随后的气道攻击后导致嗜酸性气道炎症。我们假设吸入气相甲苯二异氰酸酯 (TDI) 将导致小鼠的免疫敏化，随后的挑战将诱导病理和免疫系统改变，表明在人类中发现哮喘。为了确定暴露剂量的影响以及免疫 (过敏) 或非免疫机制的参与，建立了TDI哮喘的小鼠模型，并在低水平亚慢性或高剂量急性吸入TDI暴露后进行了表征。C57BL/6 j小鼠通过亚时吸入6周 (20 ppb，4小时/天，5天/周) 或通过2小时急性暴露于500 ppb暴露于TDI。两组在14天后通过吸入20 ppb TDI攻击1小时。接受亚慢性暴露方案的小鼠表现出明显的过敏反应，表现为气道炎症，嗜酸性粒细胞增多，杯状细胞化生，上皮细胞改变，气道高反应性 (AHR)，T(H)1/T(H)2细胞因子表达增加。肺，血清IgE水平升高，和TDI特异性IgG抗体，以及将这些病理转移到具有TDI暴露小鼠的淋巴细胞或血清的幼稚小鼠的能力。相反，接受急性TDI暴露的小鼠表现出与哮喘一致的AHR，特异性IgG抗体和肺部病理升高，但没有血清IgE升高，肺嗜酸性粒细胞或T(H) 细胞因子表达增加。这些结果描述了TDI哮喘的小鼠模型，与职业性哮喘工人的模型一致，并表明与TDI相关的肺部病理可以根据暴露范例而变化。

BACKGROUND & AIMS: :Toluene diisocyanate (TDI) induces respiratory allergy in mammals. Using immunohistochemistry and in situ hybridization histochemistry, the present study examined effects of nasal mucosa sensitization by TDI on the immunoreactivity for substance P (SP) and calcitonin gene-related peptide (CGRP) and on the expression of their mRNAs in guinea pig trigeminal ganglion and their terminals. Single intranasal application of TDI (acute experiment) did not induce nasal allergy-like behaviours and failed to cause changes of SP and CGRP immunoreactivity and in the expression of preprotachykinin A (PPTA) mRNA and preproCGRP mRNA coding for SP and CGRP respectively in the trigeminal ganglion neurons. However, repeated application of TDI (chronic experiment) caused a dramatic increase of SP and CGRP immunoreactivity in peripheral neurites of sensory nerves in the nasal mucosa but a slight increase in the spinal trigeminal nucleus, a decrease of the same immunoreactivities in the cell bodies of the trigeminal ganglion neurons, and an increase of the expression of PPTA and preproCGRP mRNA in the same neurons. These findings suggest that chronic exposure of the nasal mucosa to TDI apparently causes enhancement of both the biosynthesis of SP and CGRP and their axonal transport in the trigeminal system.

背景与目标： 甲苯二异氰酸酯 (TDI) 诱发哺乳动物的呼吸道过敏。本研究使用免疫组织化学和原位杂交组织化学方法，研究了TDI对p物质 (SP) 和降钙素基因相关肽 (CGRP) 的免疫反应性及其在豚鼠三叉神经节及其末端的mrna表达的影响。TDI (急性实验) 的单次鼻内应用不会引起鼻过敏样行为，并且未能引起SP和CGRP免疫反应性的变化以及三叉神经节神经元中分别编码SP和CGRP的protachykinin A (PPTA) mRNA和preproCGRP mRNA的表达。然而，反复应用TDI (慢性实验) 导致鼻粘膜感觉神经末梢神经突中SP和CGRP免疫反应性急剧增加，但脊髓三叉神经核略有增加，三叉神经节神经元细胞体中相同的免疫反应性降低，在相同的神经元中，PPTA和preproCGRP mRNA的表达增加。这些发现表明，鼻粘膜长期暴露于TDI显然会导致SP和CGRP的生物合成及其在三叉神经系统中的轴突转运的增强。

BACKGROUND & AIMS: :Thirty factory workers whose annual exposure to TDI amounted to 280 hours were examined. Seven of them had been removed from their jobs for presenting respiratory symptomatology and a further five were removed for presenting bronchial asthma. Their medical histories were consulted and further measures were taken such as a radiological thorax study, total IgE, TDI, MDI and HDI RAST, a basal spirometric study and finally a provocation test. The Rast proved negative in every case. In the spirometric study carried out on the provocation test, four cases showed a significant decrease in the FEV1 over 20% and over 40% in the FMEF and PEFR. There was no connection between the four patients who presented an elevated total IgE and the four who presented a positive provocation test. The provocation test proved negative in five of the seven patients removed from their places of work. Two of the four workers who responded positively to the provocation test remained in their places of work during the TDI foam test without showing any symptoms. The patients who presented symptoms did not appear to present bronchial obstruction during the provocation test. Nonetheless, patients who seemingly had not shown any symptoms presented what appeared to be bronchial obstruction.

背景与目标： : 检查了30名工厂工人，他们每年接触TDI达280小时。其中有7人因出现呼吸症状而被撤职，另有5人因出现支气管哮喘而被撤职。查阅了他们的病史，并采取了进一步的措施，例如放射学胸部研究，总IgE，TDI，MDI和HDI RAST，基础肺活量研究，最后是激发试验。Rast在每种情况下都被证明是否定的。在对激发试验进行的肺活量测定研究中，有4例显示FEV1随20% 和FMEF和PEFR随40% 而显着降低。总IgE升高的四名患者与激发试验阳性的四名患者之间没有联系。在离开工作场所的七名患者中，有五名被证明是阴性的。对挑衅测试做出积极反应的四名工人中有两名在TDI泡沫测试期间仍留在工作地点，没有出现任何症状。在激发试验中出现症状的患者似乎没有出现支气管阻塞。尽管如此，似乎没有表现出任何症状的患者似乎出现了支气管阻塞。

BACKGROUND & AIMS: :We have recently introduced a novel MRI methodology, so-called super resolution track-density imaging (TDI), which produces high-quality white matter images, with high spatial resolution and exquisite anatomical contrast not available from other MRI modalities. This method achieves super resolution by utilising the long-range information contained in the diffusion MRI fibre tracks. In this study, we validate the super resolution property of the TDI method by using in vivo diffusion MRI data acquired at ultra-high magnetic field strength (7 T), and in silico diffusion MRI data from a well-characterised numerical phantom. Furthermore, an alternative version of the TDI technique is described, which mitigates the track length weighting of the TDI map intensity. For the in vivo data, high-resolution diffusion images were down-sampled to simulate low-resolution data, for which the high-resolution images serve as a gold standard. For the in silico data, the gold standard is given by the known simulated structures of the numerical phantom. Both the in vivo and in silico data show that the structures that could be identified in the TDI maps only after using super resolution were consistent with the corresponding structures identified in the reference maps. This supports the claim that the structures identified by the super resolution step are accurate, thus providing further evidence for the important potential role of the super resolution TDI methodology in neuroscience.

背景与目标： : 我们最近推出了一种新颖的MRI方法，即所谓的超分辨率轨迹密度成像 (TDI)，该方法可产生高质量的白质图像，具有其他MRI方式无法提供的高空间分辨率和精美的解剖对比度。该方法通过利用扩散MRI光纤轨迹中包含的远程信息来实现超分辨率。在这项研究中，我们通过使用在超高磁场强度 (7 T) 下获得的体内扩散MRI数据以及来自特征良好的数值模型的计算机扩散MRI数据来验证TDI方法的超分辨率。此外，描述了TDI技术的替代版本，该技术减轻了TDI地图强度的轨道长度加权。对于体内数据，对高分辨率扩散图像进行下采样以模拟低分辨率数据，其中高分辨率图像作为金标准。对于计算机数据，金标准由数值体模的已知模拟结构给出。体内和计算机数据均表明，仅在使用超分辨率后才能在TDI图中识别出的结构与参考图中识别出的相应结构一致。这支持了通过超分辨率步骤确定的结构是准确的说法，从而为超分辨率TDI方法论在神经科学中的重要潜在作用提供了进一步的证据。

BACKGROUND & AIMS: BACKGROUND:The therapeutic use of Kampo medicine, Sho-seiryu-to (SST) in allergic disorders is well known. As histamine plays a central role in allergic diseases, it is possible that SST affects the allergy-related histamine signaling. In this study, we investigated the effect of SST on allergy-related histamine signaling in the nasal mucosa of toluene 2, 4-diisocyanate (TDI)-sensitized nasal allergy model rats. METHODS:Six-week-old male, Brown Norway rats were sensitized for 2 weeks with 10 microl of 10% TDI, and after a 1 week interval, provocation was initiated with the same amount of TDI. SST (0.6g/rat) was given orally 1 hour before TDI treatment began for a period of 3 weeks. Nasal symptoms were scored for 10 minutes immediately after TDI-provocation. The genes expression in nasal mucosa was determined using real-time quantitative RT-PCR. RESULTS:SST significantly suppressed TDI-induced nasal allergy-like symptoms. TDI provocation showed a significant up-regulation of histamine H(1) receptor (H1R) and histidine decarboxylase (HDC) gene expressions. Prolonged pre-treatment of SST significantly suppressed the mRNA levels of H1R and HDC that was up-regulated by TDI. SST also suppressed TDI-induced interleukin (IL)-4 and IL-5 mRNA elevation. However, SST showed no significant effect for TDI-induced mRNA elevation of IL-13. CONCLUSIONS:These results demonstrate that SST alleviates nasal symptoms by the inhibition of histamine signaling through suppression of TDI-induced H1R and HDC gene up-regulation. SST also suppresses cytokine signaling through suppression of IL-4 and IL-5 gene expression. Suppression of histamine signaling may be a novel mechanism of SST in preventing allergic diseases.

背景与目标：

BACKGROUND & AIMS: :Polyurethanes (PU) are polymers made with diisocyanates such as MDI (4,4'-methylene diphenyl diisocyanate) and TDI (2,4-toluene diisocyanate and 2,6-toluene diisocyanate). Investigations have been undertaken with MDI and TDI to assess dermal uptake and resulting systemic exposure. Absorption, distribution and excretion of MDI was studied in rats using a single dermal administration of (14)C-MDI dissolved in acetone at nominal 165 mg/kg body weight and 15 mg/kg bw (4.0 and 0.4 mg/cm(2)) and intradermal injection of (14)C-MDI dissolved in corn oil at nominal 1.4 mg/kg bw. Dermal absorption of (14)C-MDI (at both doses) was low; at or below 1% of the applied dose. Considerable amounts of the applied radioactivity were found at the application site which could not be washed off. By intradermal administration of (14)C-MDI approximately 66% of applied radioactivity remained at the application site with approximately 26% recovered in excreta, cage wash, tissues and carcass. The absorption, distribution and excretion of 2,4-TDI was studied in rats following a single dermal administration of radiolabelled (14)C-2,4-TDI at nominal 350 mg/kg body weight (12 mg/cm(2)). Dermal absorption of (14)C-2,4-TDI was at or below 1% of the applied dose. Considerable amounts of the applied radioactivity were found at the application site which could not be washed off. In summary the results show that dermal uptake of MDI and TDI is very low. Due to the chemical reactivity of isocyanates it can be expected that small amounts which might be absorbed will react with tissue constituents directly at the exposed skin area, or will be converted to adducts with biomacromolecules or to biologically inactive oligoureas. Overall it is concluded that, following dermal exposure to MDI and TDI, systemic exposures and resulting toxicity, other than the known sensitization, can be expected to be very low. In addition studies were performed with dermal application of unlabelled 2,4 and 2,6 TDI to check the availability and fate of this chemical on rat skin surface and to assess possible tissue damage. These experiments showed that unchanged test material can be detected on rat skin for up to 8h if not washed off. Dermal treatment with 2,4 or 2,6 TDI was associated with irritation with increased severity over a 48 h period after washing with a decontaminant solution.

背景与目标： 聚氨酯 (PU) 是用二异氰酸酯如MDI (4,4 '-亚甲基二苯基二异氰酸酯) 和TDI (2,4-甲苯二异氰酸酯和2,6-甲苯二异氰酸酯) 制备的聚合物。已经对MDI和TDI进行了调查，以评估皮肤摄取和由此产生的全身暴露。吸收，在大鼠中研究了MDI的分布和排泄，使用 (14)C-MDI溶解在丙酮中的名义165 mg/kg体重和15 mg/kg体重 (4.0和0.4 mg/cm(2)) 和皮内注射 (14)C-MDI溶解在名义1.4 mg/kg bw的玉米油中。(14)C-MDI (在两种剂量下) 的皮肤吸收低; 处于或低于所施加剂量的1%。在施用部位发现了大量的放射性，无法洗掉。通过皮内施用 (14)C-MDI，大约66% 施加的放射性留在施用部位，大约26% 在排泄物、笼洗、组织和胴体中回收。在大鼠中以标称350 mg/kg体重 (12 mg/cm(2)) 单次皮肤施用放射性标记的 (14)C-2，4-TDI后，研究了2,4-tdi的吸收，分布和排泄。(14)C-2，4-TDI的皮肤吸收处于或低于施加剂量的1%。在施用部位发现了大量的放射性，无法洗掉。总而言之，结果表明，MDI和TDI的皮肤吸收非常低。由于异氰酸酯的化学反应性，可以预期可能被吸收的少量将直接与暴露的皮肤区域的组织成分反应，或者将转化为具有生物大分子的加合物或转化为具有生物活性的寡聚体。总体而言，得出的结论是，在皮肤暴露于MDI和TDI之后，除已知的致敏作用外，全身暴露和由此产生的毒性可望非常低。此外，还进行了皮肤应用未标记2,4和2,6 TDI的研究，以检查这种化学物质在大鼠皮肤表面的可用性和命运，并评估可能的组织损伤。这些实验表明，如果不洗掉，可以在大鼠皮肤上检测到未改变的测试材料长达8小时。在用去污溶液洗涤后的48小时内，用2,4或2,6 TDI进行的皮肤治疗与刺激有关，其严重程度增加。

BACKGROUND & AIMS: AIM:To detect whether there is Helicobacter pylori (H pylori) colonization in the pharynx mucous membrane of healthy people and whether chronic pharyngitis is related to H pylori infection. METHODS:Fifty cases of chronic pharyngitis refractory over three months were prospectively studied from March 2004 to August 2004 in the otolaryngology outpatient department of the Second Hospital of Xi'an Jiaotong University. Template-directed dye-terminator incorporated with fluorescence polarization detection (TDI-FP) and modified Giemsa stain were used to examine pharynx mucous membrane tissue for H pylori colonization in the patients with chronic pharyngitis and the healthy people as a control group. RESULTS:In the control group, no people were detected to have H pylori in the pharynx. In contrast, in 50 cases with chronic pharyngitis, 19 (38.0%) cases were H pylori positive with a TDI-FP assay and 4 (8%) cases were TDI-FP positive with Giemsa staining in the pharynx. Sixteen of the 50 pharyngitis cases had stomach ailment history, 11 cases (68.8%) of these 16 patients were determined to be H pylori positive in the pharynx with the TDI-FP assay. c2 test showed that this infection rate was remarkably higher (P=0.0007) than that in the cases without stomach ailment history. Giemsa staining showed that 3 cases (18.8%) of the patients with stomach ailment history were infected with H pylori in the pharynx, which was remarkably higher (P=0.042) than that in the patients without stomach ailment history (1 case, which was 2.9%). CONCLUSION:H pylori may not be detected in the pharynx of healthy people. Chronic pharyngitis may be related to H pylori infection. The infection rate with H pylori in the pharynx is higher in patients with stomach ailment histories than in patients without stomach ailment histories, suggesting that chronic pharyngitis may be related to stomach ailment history.

背景与目标：

BACKGROUND & AIMS: :Toluene diisocyanate (TDI), a highly reactive industrial chemical is one of the leading causes of occupation-related asthma in industrialized countries. The pathophysiology of TDI-induced asthma, however, remains poorly understood, in part due to a lack of appropriate animal models. In this study, four models of TDI-sensitised mice were investigated. In model number 1, the mice were sensitised for 4 h/day on four consecutive days to 3 ppm inhaled TDI and challenged twice for 4 h each time with 0.3 ppm inhaled TDI. In model number 2, the sensitising condition was similar to that of model 1, but the challenge conditions involved an initial inhalation of 2 ppmTDI for 4h and then tracheal instillation with 50 microg/mouse albumin-TDI. In model number 3, the mice were sensitised first to 25% TDI (sc) and then three times for 4 h each time to 1 ppm inhaled TDI and challenged twice for 4h each time with 0.1 ppm inhalated TDI. In model number 4, the mice were first sensitised to 1% TDI by skin application and then with 0.2% TDI by tracheal instillation and challenged tree times by tracheal instillation of 0.1% TDI. In model number 4, skin application followed by tracheal instillations of TDI led to local and systemic Th2-dominated immune responses that were characterized: (1) in the lung-associated lymph nodes by a decrease in Th1 cytokine (IFN-gamma) production associated with an increase in Th2 cytokine (IL-4, IL-5, IL-3) production; (2) in the lungs by an allergic inflammation throughout the conducting airways: goblet cell proliferation and eosinophil influx and; (3) in the serums by increased total and specific IgE levels, 17.5- and 3.5-fold higher than that of the controls, respectively. The conditions used for sensitisation in the other models, i.e. inhalation or subcutaneous administration plus inhalation, failed to induce a strong Th2 response like that observed in model number 4. The findings indicate that TDI can induce a Th2-dominated response in mice when administered by topical application plus tracheal instillation for sensitisation and by intra-tracheal instillation for challenge (model number 4). This mouse Th2 model of TDI-induced airway allergy can, in several aspects, mimic occupational TDI asthma in humans and may prove to be useful in determining the mechanistic basis behind this disease.

背景与目标： 甲苯二异氰酸酯 (TDI) 是一种高反应性的工业化学品，是工业化国家与职业相关的哮喘的主要原因之一。然而，TDI诱导的哮喘的病理生理学仍然知之甚少，部分原因是缺乏合适的动物模型。在这项研究中，研究了四种TDI致敏小鼠模型。在模型1中，小鼠连续4天对3 ppm吸入的TDI致敏4小时/天，并用0.3 ppm吸入的TDI攻击两次，每次4小时。在模型2中，致敏条件与模型1相似，但是攻击条件包括最初吸入2 ppmTDI 4小时，然后气管滴注50 microg/小鼠白蛋白-TDI。在模型3中，首先使小鼠致敏以25% TDI (sc)，然后三次，每次4小时，以lppm吸入TDI，并且用0.1 ppm吸入TDI攻击两次，每次4小时。在模型4中，首先通过皮肤施用使小鼠对1% TDI敏感，然后通过气管滴注0.2% TDI，并通过气管滴注0.1% TDI来激发树时间。在4号模型中，皮肤应用，然后气管滴注TDI导致局部和全身Th2-dominated免疫反应，其特征是 :( 1) 在肺相关淋巴结中，Th1细胞因子 (IFN-γ) 的产生减少，Th2细胞因子的增加 (IL-4，IL-5，IL-3) 产生; (2) 在肺部通过整个传导气道的过敏性炎症: 杯状细胞增殖和嗜酸性粒细胞流入; (3) 在血清中通过增加总IgE水平和特异性IgE水平，分别比对照组高17.5倍和3.5倍。在其他模型中用于致敏的条件，即吸入或皮下给药加吸入，未能像在模型4中观察到的那样引起强烈的Th2反应。研究结果表明，当通过局部应用加气管滴注致敏和气管内滴注致敏 (模型4) 给药时，TDI可以在小鼠中诱导Th2-dominated反应。这种TDI诱导的气道过敏的小鼠Th2模型可以在几个方面模仿人类的职业性TDI哮喘，并且可能被证明可用于确定该疾病背后的机制基础。

BACKGROUND & AIMS: OBJECTIVE:Superior global cardiac performance (ie stroke volume) is classically reported after training in children. Current knowledge of the impact of exercise training on myocardial relaxation, a major component of left ventricular (LV) filling and subsequently stroke volume, is, however, limited in the paediatric population. This study aimed to investigate the effect of aerobic training on LV wall motion velocities by tissue Doppler imaging (TDI) in healthy children. METHODS:25 children (11 girls, 14 boys) were enrolled in a 2 month high-intensity aerobic training programme and 25 (12 girls and 13 boys) served as controls. The children (9-11 years old) performed a graded maximal exercise test on a treadmill to evaluate maximal oxygen uptake. Standard Doppler echocardiography and TDI measurements were performed at baseline and end of the study. Tissue Doppler systolic, early and late myocardial velocities were obtained at the mitral annulus in the septal, lateral, inferior and posterior walls. RESULTS:Maximal oxygen uptake increased by 6.5% (before: 51.6 (SD 4.2), after: 55.0 (4.5) ml/min/kg p<0.001) after training. A modest but significant increase in left ventricular end-diastolic diameter was also noticed (before: 46.1 (3.4), after: 48.3 (4.3) mm.BSA(-1/2), p<0.001), whereas left ventricular wall thickness and mass were unchanged. Neither transmitral inflow velocities nor early and late wall motion (Em: before = 18.4 (2.7), after = 18.0 (2.3) cm/s, Am: before = 6.8 (1.2), after = 6.7 (1.3) cm/s) were affected by training. Shortening fraction and regional systolic function (Sm: before = 10.1 (1.6), after = 10.2 (1.4) cm/s) by TDI were also unchanged. CONCLUSION:High-intensity aerobic sessions repeated over a 2 month period failed to improve regional diastolic function assessed by TDI in healthy young children.

背景与目标：