晕可宁颗粒对急、慢性梅尼埃病模型的影响

目的　探讨晕可宁颗粒的主要药效学 ,为临床提供药效学资料及治疗学基础。方法　采用三氯甲烷破坏豚鼠一侧膜迷路感受器模型 ,探讨受试药对眼震颤、摆头及旋转的影响 ;采用内淋巴囊和内淋巴管阻塞手术复制豚鼠膜迷路实验性膜迷路积水模型 ,研究内耳组织平均中阶面积 (SMA)增加率及形态学的变化。结果　抑眩宁阳性对照组、晕可宁颗粒 (8、16g/kg)模型给药组豚鼠眼球震颤次数减少 ,差异有显著意义 (P <0 .0 5 )。成功复制了不同程度膜迷路积水豚鼠模型 ,表现为前庭膜重度膨出 ,前庭阶缩小 ,膜蜗管增大 ,SMA增加率变大 ,差异有显著意义 (P <0 .0 1) ;晕可宁颗粒灌胃后可减轻豚鼠实验性膜迷路积水的程度 ,差异有显著意义 (P <0 .0 1) ;但与空白对照组比较SMA增加率差异无显著意义 (P >0 .0 5 )。结论　晕可宁颗粒可以减轻内淋巴囊积水程度 ,对梅尼埃病症状有对抗治疗作用。     

Mucosal bromodomain-containing protein 4 mediates aeroallergen-induced inflammation and remodeling

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Inhibitory Effects of Incomplete Freund's Adjuvant on Experimental Autoimmune Encephalomyelitis

Freund's incomplete adjuvant (IFA), an aqueous/oil emulsion that is widely used in combination with antigenic proteins and peptides to induce tolerance, is considered to be immunologically inert. However, sporadic reports indicate that IFA may itself have inhibitory properties on induction of adjuvant induced arthritis and spontaneous diabetes. In the current study, the effects of IFA/saline were evaluated on the induction of experimental autoimmune encephalomyelitis (EAE) in three different strains of mice. IFA/saline given i.p. in two doses of >100 &#117 &#119 l 10 &#117 days apart were found to inhibit EAE induction to varying degrees in all three strains of mice in a dose dependent fashion. The IFA/saline injections inhibited both mitogen and antigen-induced T cell proliferation, induced elevated secretion of IFN- &#110 and IL-10 by neuroantigen specific T cells, and reduced expression of cytokines, chemokines, and chemokine receptors of CNS-infiltrating mononuclear cells. These data demonstrate for the first time a direct inhibitory effect of IFA/saline on EAE, and re-emphasize the need to properly control experiments using IFA to induce antigen-specific tolerance.     

Towards improved diagnosis of von Willebrand disease: Comparative evaluations of several automated von Willebrand factor antigen and activity assays

Introduction

von Willebrand disease (VWD) is reportedly the most common bleeding disorder and arises from deficiency and/or defects of von Willebrand factor (VWF). Laboratory diagnosis and typing has important management implications and requires a wide range of tests, including VWF activity and antigen, and involves differential identification of qualitative vs quantitative defects.

Methods

We have assessed several VWF antigen and activity assays (collagen binding [VWF:CB], ristocetin cofactor [VWF:RCo] and the new Siemens INNOVANCE assay [VWF:Ac], employing latex particles and gain of function recombinant glycoprotein Ib to facilitate VWF binding and agglutination without need for ristocetin) using different instrumentation, including the new Sysmex CS-5100, with a large sample test set (n = 600). We included retrospective plus prospective study designs, and also evaluated desmopressin responsiveness plus differential sensitivity to high molecular weight VWF.

Results

VWF:Ag and VWF:RCo results from different methods were respectively largely comparable, although some notable differences were evident, including one high false normal VWF:Ag value (105 U/dL) on a type 3 VWD sample, possibly due to heterophile antibody interference in the latex-based CS-5100 methodology. VWF:Ac was largely comparable to VWF:RCo, but VWF:CB showed discrepant findings to both VWF:RCo and VWF:Ac with some patients, most notably patients with type 2M VWD.

Conclusions

(a) VWF:Ag on different platforms are largely interchangeable, as are VWF:RCo on different platforms, except for occasional (some potentially important) differences, and manufacturer recommended methods may otherwise require some assay optimization; (b) VWF:RCo and VWF:Ac are largely interchangeable, except for occasional differences that may also relate to assay design (differing optimizations); (c) VWF:CB provides an additional activity to supplement VWF:RCo or VWF:Ac activity assays, and is not interchangeable with either.     

Associations between Dietary Patterns and Cardiometabolic Risk Factors—A Longitudinal Analysis among High-Risk Individuals for Diabetes in Kerala,India

The association between dietary patterns and cardiometabolic risk factors is not well understood among adults in India, particularly among those at high risk for diabetes. For this study, we analyzed the data of 1007 participants (age 30–60 years) from baseline and year one and two follow-ups from the Kerala Diabetes Prevention Program using multi-level mixed effects modelling. Dietary intake was measured using a quantitative food frequency questionnaire, and dietary patterns were identified using principal component analysis. Two dietary patterns were identified: a “snack-fruit” pattern (highly loaded with fats and oils, snacks, and fruits) and a “rice-meat-refined wheat” pattern (highly loaded with meat, rice, and refined wheat). The “snack-fruit” pattern was associated with increased triglycerides (mg/dL) (β = 6.76, 95% CI 2.63–10.89), while the “rice-meat-refined wheat” pattern was associated with elevated Hb1Ac (percentage) (β = 0.04, 95% CI 0.01, 0.07) and central obesity (OR 1.16, 95% CI 1.01, 1.34). These findings may help inform designing dietary interventions for the prevention of diabetes and improving cardiometabolic risk factors in high-diabetes-risk individuals in the Indian setting.     

艾灸神阙穴对不同程度力竭运动大鼠海马区单胺类神经递质的影响

目的:探讨艾灸神阙穴对不同程度力竭运动大鼠海马区单胺类神经递质的影响。方法:将72只SD雄性大鼠按随机数字表法分为正常组8只、模型组和艾灸组各32只,根据造模或治疗时间将模型组和艾灸组随机分为1、4、7、10次亚组,每亚组8只,采用游泳实验建立力竭模型。艾灸各亚组大鼠造模后即刻温和灸神阙穴15min,隔日1次,各亚组大鼠完成相应力竭运动后24 h检测海马组织5-HT、DA、NE的含量。结果:与正常组比较,模型各亚组5-HT含量均明显升高,模型1、4、7次亚组NE含量均明显升高,模型1次亚组DA含量明显升高,模型10次亚组却明显降低。与相应模型亚组比较,艾灸4次亚组NE含量明显升高,艾灸7、10次亚组5-HT含量显著降低,DA、NE含量明显升高。结论:艾灸神阙穴可以通过调节反复力竭运动大鼠海马区神经递质,促进神经细胞的功能恢复,改善机体疲劳状态,为今后临床应用提供一定的实验基础。     

Progestin-inducible EDD E3 ubiquitin ligase binds to α4 phosphoprotein to regulate ubiquitination and degradation of protein phosphatase PP2Ac

Mammalian α4 phosphoprotein binds to the protein phosphatase 2A catalytic subunit (PP2Ac) to regulate PP2A activity, and to poly(A)-binding protein (PABP) and progestin-inducible EDD E3 ubiquitin ligase. This study showed induction of the EDD protein by progesterone, 17β-estradiol and prolactin in breast cancer cells. Co-immunoprecipitation analyses, using lysates of COS-1 cells transfected with α4-deletion constructs, showed the α4 N-terminus binding to endogenous PP2Ac and PABP, and the C-terminus to EDD. Monoubiquitinated α4 in MCF-7 cells was unaffected by EDD-targeting siRNA (siEDD) nor by non-targetting siNT, thus, EDD does not ubiquitinate α4. PP2Ac is polyubiquitinated, and 36-kDa PP2Ac only was detected in siEDD- or siNT-transfected cells. However, treatment with proteasomal inhibitor MG132 showed polyubiquitinated-PP2Ac molecules (∼65–250 kDa) abundantly in siNT controls but low in siEDD-transfectants, implicating PP2Ac as an EDD substrate. Finally, progesterone induction of EDD in MCF-7 cells correlated with decreased PP2Ac levels, further implicating hormone-inducible EDD in PP2Ac turnover.     

卡介菌多糖核酸治疗小儿咳嗽变异性哮喘

目的：观察卡介菌多糖核酸注射液在小儿咳嗽变异性哮喘治疗应用的疗效。方法：将本科40例咳嗽变异性哮喘患儿，随机分为治疗组和对照组（各20例）。治疗组给予BCG—PSN＋必可酮气雾剂，对照组：给予单用必可酮气雾剂吸入，连续吸入6周，观察疗效，并进行统计学处理。结果：治疗组总有效率为95％，对照组总有效率为70％，统计学处理总有效率有显著差异（P〈O．01）。结论：卡介菌多糖核酸（polysaccharide nucleic acidfraction of BCG，BCG—PSN）能有效地控制咳嗽变异性哮喘（CVA）的呼吸道的反复感染，提高免疫功能；与必可酮配合，能有效地控制CVA的复发。