氮卓斯汀对哮喘豚鼠炎症细胞粘附功能的影响

目的研究组胺H1 受体拮抗剂氮卓斯汀(Azelastine ,AZT)对哮喘豚鼠炎症细胞粘附功能的影响,探讨氮卓斯汀拮抗哮喘气道炎症的可能机制。方法以卵白蛋白致敏豚鼠制备哮喘模型。采用密度梯度离心法分离并计数支气管肺泡灌洗液(BALF)中嗜酸性粒细胞(EOS)和淋巴细胞(LC)的数量;采用ELISA法检测血浆和BALF中可溶性细胞间粘附分子 1(sICAM 1)和可溶性P选择素(sP S)的含量。通过荧光酶标记法在pharmaciaCAPSystem中测定血清和BALF中嗜酸性粒细胞阳离子蛋白(ECP)的水平。结果氮卓斯汀能显著降低哮喘豚鼠BALF中Eos和LC的数量;在氮卓斯汀治疗组,哮喘豚鼠血浆和BALF中sICAM 1和sP S的含量均显著降低,血清和BALF中ECP的含量也显著降低,与模型组相比均有显著性差异。结论氮卓斯汀能降低哮喘豚鼠sICAM 1、sP S和ECP的水平,抑制Eos和LC的粘附,减少其在气道的浸润。这可能是组胺H1 受体拮抗剂氮卓斯汀拮抗哮喘气道炎症的重要机制之一。     

哮喘小鼠下呼吸道流感嗜血杆菌定植的研究

目的：建立哮喘合并下呼吸道流感嗜血杆菌定植小鼠模型,并进行评价。方法：将80只小鼠按随机数字表法分为正常组、正常注菌（流感嗜血杆菌）组 、哮喘组 、哮喘注菌（流感嗜血杆菌）组。哮喘组、哮喘注菌组用卵清蛋白（ovalbumin, OVA）致敏和激发小鼠制作哮喘模型,正常注菌组、哮喘注菌组小鼠气管内滴注琼脂包被的流感嗜血杆菌,每组各取一半小鼠分别在气道滴注之后的第7天和第21天处死,取肺组织进行病理观察,行气管细菌培养,测定肺泡灌洗液（broncheoalveolar lavage fluid,BALF）的细胞计数,检测血清和BALF中肿瘤坏死因子α（tumor necrosis factor α,TNF-α）水平。结果：与正常注菌组及哮喘组（未注菌）相比,哮喘注菌组小鼠有明显的哮喘和感染表现;病理学结果显示其气道管壁增厚、黏膜水肿,管腔内有黏液分泌,且有大量炎症细胞浸润;气道形态学参数分析显示,其气管壁及气管平滑肌增厚;BALF中白细胞总数和中性粒细胞计数增多;血清和BALF中TNF-α水平升高;注菌后第7天和第21天气管细菌培养可见流感嗜血杆菌。结论：用OVA制备哮喘动物模型,并在气道内注入琼脂包被的流感嗜血杆菌,可以建立哮喘合并呼吸道流感嗜血杆菌定植的动物模型,造成肺部气道重塑和炎症反应。     

孟鲁司特、地塞米松对哮喘小鼠气道重构及血清VEGF水平的干预作用

目的支气管哮喘是以嗜酸粒细胞、淋巴细胞及肥大细胞浸润为主的气道慢性变态反应性炎症。哮喘患者气道组织慢性炎症的同时常伴气道重构，它以杯状细胞、平滑肌细胞增生、基底膜变厚、上皮下纤维化和粘膜下血管增生为特征；且气道重构与多种生长因子有关。方法本实验选择慢性哮喘小鼠模型，初步研究孟鲁司特(Montelukast，MK)和地塞米松(dexamethasone，DXM)对小鼠血清VEGF和气道重构的影响。分别观察经管喂孟鲁司特和腹腔注射地塞米松后的哮喘小鼠肺组织切片的病理改变；用EIA法检测哮喘小鼠血清中VEGF水平。结论MK和DXM能明显降低哮喘小鼠血清中VEGF水平，两者均有助于改善哮喘小鼠的气道重构。     

瘦素在肥胖哮喘小鼠气道重构中的作用

目的探讨脂肪因子瘦素在支气管哮喘气道重构中的作用。方法高脂饮食制造肥胖模型,经腹腔注射与雾化吸入卵蛋白(OVA)制作慢性哮喘模型。45只雌性C57/6J小鼠随机分为对照组,单纯哮喘组,肥胖哮喘组,每组15只,于末次激发48 h内处死小鼠;计数支气管肺泡灌洗液(BALF)中细胞总数及分类,肺组织HE观察各组小鼠肺组织病理变化及ELISA法测定血清中瘦素水平。结果肥胖哮喘组小鼠BALF中白细胞总数及嗜酸性粒细胞比例以及气道管壁厚度和气道平滑肌厚度均较单纯哮喘组和对照组显著增加(P0.05)。对照组血清瘦素为(1 438.54±208.14)pg/mL,明显低于单纯哮喘和肥胖哮喘组[(1 677.75±214.36)pg/mL,(2 114.20±189.15)pg/mL,P0.05)],血清瘦素水平与气管壁厚度和气道平滑肌厚度呈正相关(P0.05)。结论肥胖通过瘦素参与了哮喘气道重构过程,纠正瘦素失衡有望成为肥胖哮喘患者治疗的新方向。     

miR-200介导的IL-33表达参与支气管哮喘 发展过程的临床和小鼠实验研究

目的探讨miR-200对支气管哮喘发病过程的影响及潜在机制。方法选取22例为哮喘患者为哮喘组,14例正常人为正常组,检测两组支气管肺泡灌洗液(BALF)中miR-200a、miR-200b、miR-200c和血清中IL-33表达,分析IL-33与miR-200a、miR-200b、miR-200c的相关性。选取40只健康雄性BALB/c小鼠随机分为4组:对照组、卵清蛋白(OVA)组、OVA+miR-200b组、OVA+miR-200c组,每组各10只。采用OVA建立实验性哮喘小鼠模型,之后用miR-200b或miR-200c寡核苷酸通过鼻腔给药干预OVA小鼠,对照组小鼠用生理盐水代替。检测各组小鼠对不同浓度醋甲胆碱的气道阻力,及血清、BALF及肺组织中IL-33的含量,肺组织中miR-200b、miR-200c、IL-4、IL-5、IL-13的水平。结果与正常组比较,哮喘组患者BALF中miR-200b和miR-200c的表达显著降低(P 0. 05),miR-200a的表达无显著变化(P0. 05),此外哮喘组患者血清IL-33的含量显著增加(P 0. 05)。哮喘组患者血清IL-33的含量与BALF中miR-200b和miR-200c的表达呈显著负相关(P 0. 05)。与对照组比较,OVA组小鼠肺组织中miR-200b和miR-200c的表达显著降低(P 0. 05),血清、BALF及肺组织中IL-33的含量显著增加(P 0. 05),肺组织中炎症因子IL-4、IL-5和IL-13含量显著增加(P 0. 05),对8 mg/ml、12 mg/ml和16 mg/ml的醋甲胆碱的气道阻力显著增加(P0. 05)。与OVA组比较,OVA+miR-200b组和OVA+miR-200c组小鼠上述指标均逆转(P 0. 05)。结论 miR-200b/c表达降低与支气管哮喘的发展有密切关系,其可通过调节IL-33信号通路,可作为哮喘治疗的靶点之一。     

小鼠过敏性哮喘模型肺组织中Th9细胞相关因子的变化及意义

目的分析小鼠过敏性哮喘模型肺组织中各细胞因子表达水平的变化,探讨它们在过敏性支气管哮喘气道炎症中的调节机制。方法选取雌性BALB/c小鼠,复制小鼠过敏性哮喘模型,提取小鼠肺组织RNA,采用荧光定量PCR检测IL-9、IL-9R和PU.1 mRNA表达水平;收集支气管灌洗液,ELISA法检测灌洗液上清中各细胞因子(IL-4、INF-γ、IL-9和OVA特异IgE)的含量,并进一步分析这些分子间的相关关系。结果两组小鼠的Penh%随Mch剂量的增加都有升高的趋势,但是模型组小鼠上升的更快;与对照组相比,模型组小鼠BALF上清液中IL-4、IL-9、OVA特异抗体IgE水平显著升高(P0.05),INF-γ水平则显著下降(P0.05);模型组小鼠肺组织中IL-9、IL-9R及PU.1 m RNA相对表达水平与对照组相比均增高;除INF-γ与IL-9呈负相关关系,其他因子间均呈显著的正相关系。结论小鼠过敏性哮喘模型肺组织中Th9细胞相关因子(IL-9、IL-9R和PU.1)表达水平显著升高,可能在哮喘气道炎症进程中起到重要的免疫调节作用,是过敏性哮喘诊断与治疗的潜在靶点。     

白三烯受体拮抗剂和激素对哮喘小鼠精氨酸酶-Ⅰ转录水平影响的研究

目的观察哮喘小鼠模型的病理特点及精氨酸酶-I在哮喘小鼠中的转录水平及白三烯受体拮抗剂和激素干预对精氨酸酶-I转录水平的影响。方法建立小鼠哮喘模型;实验分为对照组、哮喘组、孟鲁司特(MK)干预组、地塞米松(DXM)干预组;图像分析肺内支气管平滑肌厚度;阿尔新兰染色,观察粘液分泌情况;半定量PCR检测精氨酸酶-I mRNA水平。结果哮喘组出现管壁增厚、平滑肌增生、粘液分泌增加、炎症细胞浸润等特征,精氨酸酶-I mRNA水平明显增高;MK组、DXM组与哮喘组比较,炎症反应轻微,平滑肌增生、粘液分泌不明显;DXM组精氨酸酶-mRNA水平降低,与哮喘组比较差异有显著性。结论少量、多次变应原吸入可导致气道炎症和重构,精氨酸酶-I在哮喘小鼠中的表达水平升高,DXM干预可降低精氨酸酶-I mRNA水平,一定程度上延缓气道重构的发生。     

哮喘小鼠气道炎症与活化T细胞核因子c1的相关性及尼卡地平对其的干预作用

目的:探讨活化T细胞核因子c1(nuclear factor of activated T cells c1,NFATc1)与气道炎症的相关性,观察尼卡地平对哮喘小鼠气道炎症以及NFATc1蛋白表达的影响.方法:建立哮喘小鼠模型并收集支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF),ELISA法测定BALF中细胞因子IL-4、IL-5和IFN-γ的水平,免疫组化法测定气道周围淋巴细胞中NFATc1蛋白的表达.结果:IL-4、IL-5的水平与NFATc1阳性率有线性正相关(P<0.05).哮喘小鼠IL-4、IL-5水平以及NFATc1蛋白表达较正常组升高,差异有统计学意义(P<0.05):尼卡地平干预组IL-4、IL-5水平和NFATc1表达较哮喘组降低,差异有统计学意义(P<0.05).结论:NFATc1的激活可上调IL-4和IL-5的表达,促进哮喘的气道炎症;尼卡地平可抑制NFATc1的表达,降低细胞因子IL-4、IL-5的水平,减轻哮喘气道炎症.     

雾化吸入细辛脑对哮喘小鼠中白细胞介素25水平的影响

目的观察细辛脑对哮喘小鼠血清、肺泡灌洗液和肺组织中IL-25浓度的影响,初步探讨细辛脑在哮喘小鼠治疗中的作用。方法取40只6~8周龄的雌性BALB/c小鼠,随机分为对照组、哮喘组、细辛脑组、地塞米松组,每组10只,采用鸡卵白蛋白(chicken ovalbumin)致敏和激发小鼠建立哮喘模型,对照组均以生理盐水代替;HE染色观察小鼠肺组织病理变化;光学显微镜下计数小鼠外周血中嗜酸粒细胞及白细胞总数;用酶联免疫吸附法(ELISA)测定小鼠血清及支气管肺泡灌洗液(BALF)中白细胞介素-25(IL-25)浓度;用免疫荧光实时定量方法(RT-PCR)检测小鼠肺组织中IL-25 m RNA的表达水平。结果 HE染色可见哮喘组小鼠肺组织炎性浸润,细辛脑及地塞米松组炎性浸润程度较哮喘组轻;哮喘组中嗜酸粒细胞总数高于对照组(P<0.05),而细辛脑组及地塞米松组中嗜酸粒细胞总数均低于哮喘组,且具有统计学差异(P<0.05);哮喘组血清及BALF中IL-25的浓度较对照明显增高(P<0.05),细辛脑组及地塞米松组中IL-25的浓度比哮喘组明显降低(P<0.05);哮喘组小鼠肺组织IL-25 m RNA相对表达量明显高于对照组(P<0.05),而细辛脑组及地塞米松组均低于哮喘组(P<0.05)。结论细辛脑能减少嗜酸粒细胞及IL-25的生成,从而抑制气道炎症,减轻气道炎性反应,对治疗哮喘有一定的作用。     

血小板活化因子与支气管哮喘

血小板活化因子(platelet-activating factor,PAF)是一种内源性具有生物活性的胆碱磷脂,具有强大的致炎作用.支气管哮喘是气道慢性炎症性病变,其病理特征可概括为活性炎症细胞尤其是嗜酸性粒细胞(Eos)的浸润、气道的高反应性(AHR)以及支气管壁的重构,这三者互为因果[1-2].     

Guns and Knives in New Mexico: Patterns of Penetrating Trauma, 1978–1993

Objective: To identify patterns of nonfatal and fatal penetrating trauma among children and adults in New Mexico using ED and medical examiner data.
Methods: The authors retrospectively sampled in 5-year intervals all victims of penetrating trauma who presented to either the state Level-1 trauma center or the state medical examiner from a 16-year period (1978–1993). Rates of nonfatal and fatal firearm and stabbing injury were compared for children and adults.
Results: Rates of nonfatal injury were similar (firearm, 34.3 per 100,000 person-years; stabbing, 35.1). However, rates of fatal injury were significantly different (firearm, 21.9; stabbing, 2.7; relative risk: 8.2; 95% confidence interval: 5.4, 12.5). From 1978 to 1993, nonfatal injury rates increased for children (p = 0.0043) and adults (p < 0.0001), while fatal penetrating injury remained constant. The increase in nonfatal injury in children resulted from increased firearm injury rates. In adults, both stabbing and firearm nonfatal injury rates increased.
Conclusions: Nonfatal injury data suggest that nonfatal violence has increased; fatal injury data suggest that violent death rates have remained constant. Injury patterns vary by age, mechanism of trauma, and data source. These results suggest that ED and medical examiner data differ and that both are needed to guide injury prevention programs.     

Dissociable correlates of two classes of retrieval processing in prefrontal cortex

Although substantial evidence suggests that the prefrontal cortex (PFC) implements processes that are critical for accurate episodic memory judgments, the specific roles of different PFC subregions remain unclear. Here, we used event-related functional magnetic resonance imaging to distinguish between prefrontal activity related to operations that (1) influence processing of retrieval cues based on current task demands, or (2) are involved in monitoring the outputs of retrieval. Fourteen participants studied auditory words spoken by a male or female speaker and completed memory tests in which the stimuli were unstudied foil words and studied words spoken by either the same speaker at study, or the alternate speaker. On "general" test trials, participants were to determine whether each word was studied, regardless of the voice of the speaker, whereas on "specific" test trials, participants were to additionally distinguish between studied words that were spoken in the same voice or a different voice at study. Thus, on specific test trials, participants were explicitly required to attend to voice information in order to evaluate each test item. Anterior (right BA 10), dorsolateral prefrontal (right BA 46), and inferior frontal (bilateral BA 47/12) regions were more active during specific than during general trials. Activation in anterior and dorsolateral PFC was enhanced during specific test trials even in response to unstudied items, suggesting that activation in these regions was related to the differential processing of retrieval cues in the two tasks. In contrast, differences between specific and general test trials in inferior frontal regions (bilateral BA 47/12) were seen only for studied items, suggesting a role for these regions in post-retrieval monitoring processes. Results from this study are consistent with the idea that different PFC subregions implement distinct, but complementary processes that collectively support accurate episodic memory judgments.     

Interprofessional approaches to creating safe,high quality health care

Three supplementary perspectives are presented arguing that interprofessional collaboration is both necessary and desirable. Nonetheless, there are often too many serious intra-professional barriers and obstacles to interprofessional collaboration to make it successful. Some of these barriers, it is argued and illustrated, are found in the multiple ways in which professional identity is tacitly acquired and embodied in the practitioners' habitual, everyday practice. The paper then explores ways in which reflection, especially Second order reflection, can help to elucidate and overcome these obstacles, as well as increasing professional adaptability and competence.     

Systematic Reviews Published in the January 2011 Issue of The Cochrane Library

ABSTRACT

The Cochrane Library of Systematic Reviews is published quarterly as a DVD and monthly online. The January 2011 issue (first quarterly DVD for 2011) contains 4515 complete reviews, 1985 protocols for reviews in production, and 13,521 one-page summaries of systematic reviews published in the general medical literature. In addition, there are citations of 641,000 randomized controlled trials, and 14,018 cited papers in the Cochrane methodology register. The health technology assessment database contains over 9300 citations. One hundred and seven new reviews have been published in the last 3 months, of which five have potential relevance for practitioners in pain and palliative medicine.     

Modified micro-superior percutaneously-assisted total hip: early experiences & case reports

Because of the extensile nature and familiarity of the standard posterior-lateral approach to the hip, a family of "micro-posterior" approaches has been developed. This family includes the Percutaneously-Assisted Total Hip (PATH) approach, the Supercapsular (SuperCap) approach and a newer hybrid approach, the Supercapsular Percutaneously-Assisted Total Hip (SuperPATH) approach. Such approaches should ideally provide a continuum for the surgeon: from a "micro" (external rotator sparing) posterior approach, to a "mini" (external rotator sacrificing) posterior approach, to a standard posterior approach. This could keep a surgeon within his comfort zone during the learning curve of the procedure, while leaving options for complicated reconstructions for the more practiced micro-posterior surgeons. This paper details one author's experiences utilizing this combined approach, as well as permutations of this entire micro-posterior family of approaches as applied to more complex hip reconstructions.     

Determination of creatine kinase isoenzyme MB activity in serum using immunological inhibition of creatine kinase M subunit activity. Activity kinetics and diagnostic significance in myocardial infarction.

This is a new method for the determination of creatine kinase isoenzyme MB activity in serum. The method uses direct activity measurement of creatine kinase B subunit activity after blocking of CK-M subunit activity by inhibiting antibodies. The test takes no longer than 15 min. The method yields an intra-serial C.V. of 2.0-12.9%, and a C.V. from day to day of 5.5%. The detection limit is 3.4 U/l creatine kinase MB. In the 95 cases with proven myocardial infarction several types of creatine kinase MB activity kinetics could be determined. The percentage of creatine kinase MB of peak CK-total is 6-25%, with a mean of 11.1%. The amount of creatine kinase MB with respect to total CK activity after reinfarction is higher than the amount after initial infarction.     

Structure and function of "metalloantibiotics"

Although most antibiotics do not need metal ions for their biological activities, there are a number of antibiotics that require metal ions to function properly, such as bleomycin (BLM), streptonigrin (SN), and bacitracin. The coordinated metal ions in these antibiotics play an important role in maintaining proper structure and/or function of these antibiotics. Removal of the metal ions from these antibiotics can cause changes in structure and/or function of these antibiotics. Similar to the case of "metalloproteins," these antibiotics are dubbed "metalloantibiotics" which are the title subjects of this review. Metalloantibiotics can interact with several different kinds of biomolecules, including DNA, RNA, proteins, receptors, and lipids, rendering their unique and specific bioactivities. In addition to the microbial-originated metalloantibiotics, many metalloantibiotic derivatives and metal complexes of synthetic ligands also show antibacterial, antiviral, and anti-neoplastic activities which are also briefly discussed to provide a broad sense of the term "metalloantibiotics."