Characterization of invasive Neisseria meningitidis from Atlantic Canada, 2009 to 2013: With special reference to the nonpolysaccharide vaccine targets (PorA,factor H binding protein,Neisseria heparin-binding antigen and Neisseria adhesin A)

BACKGROUND:Serogroup B Neisseria meningitidis (MenB) has always been a major cause of invasive meningococcal disease (IMD) in Canada. With the successful implementation of a meningitis C conjugate vaccine, the majority of IMD in Canada is now caused by MenB.OBJECTIVE:To investigate IMD case isolates in Atlantic Canada from 2009 to 2013. Data were analyzed to determine the potential coverage of the newly licensed MenB vaccine.METHODS:Serogroup, serotype and serosubtype antigens were determined from IMD case isolates. Clonal analysis was performed using multilocus sequence typing. The protein-based vaccine antigen genes were sequenced and the predicted peptides were investigated.RESULTS:The majority of the IMD isolates were MenB (82.5%, 33 of 40) and, in particular, sequence type (ST)-154 B:4:P1.4 was responsible for 47.5% (19 of 40) of all IMD case isolates in Atlantic Canada. Isolates of this clone expressed the PorA antigen P1.4 and possessed the nhba genes encoding for Neisseria heparin-binding antigen peptide 2, which together matched exactly with two of the four components of the new four-component meningococcal B vaccine. Nineteen MenB isolates had two antigenic matches, another five MenB and one meningitis Y isolate had one antigenic match. This provided 75.8% (25 of 33) potential coverage for MenB, or a 62.5% (25 of 40) overall potential coverage for IMD.CONCLUSION:From 2009 to 2013, IMD in Atlantic Canada was mainly caused by MenB and, in particular, the B:4:P1.4 ST-154 clone, which accounted for 47.5% of all IMD case isolates. The new four-component meningococcal B vaccine appeared to offer adequate coverage against MenB in Atlantic Canada.     

Mediation of platelet adhesion to fibrillar collagen in flowing blood by a proteolytic fragment of human von Willebrand factor

The effect of purified von Willebrand Factor (vWF) fragments, SpII (dimer of two 110 kd subunits) and SpIII (dimer of two 170 kd subunits) obtained with S aureus V-8 protease was tested upon platelet adhesion to collagen. Purified fibrillar human collagen coated onto cover slips was incubated with SpII, SpIII, or undigested vWF and exposed to reconstituted human blood in a parallel-plate perfusion chamber at a high shear rate. Platelet-collagen interactions were estimated using 51Cr-platelets and quantitative morphometry. When blood was reconstituted with citrated autologous plasma, SpIII and vWF strikingly enhanced platelet adhesion to collagen whereas SpII had no effect. When blood was reconstituted with human albumin and divalent cations, SpIII and vWF again promoted platelet adhesion to collagen. In conclusion, our data suggest that (1) SpIII, the N-terminal portion of vWF which binds to platelet membrane glycoprotein Ib, functionally substitutes for vWF in supporting platelet adhesion to collagen; (2) SpII, the C- terminal portion which binds to glycoprotein IIb/IIIa, has no such effect; (3) in addition to its platelet binding domain, SpIII contains another site for binding to collagen; and (4) the multimeric structure of vWF is not required for platelet adhesion to collagen.     

Radiological imaging of a massive dermoid in the male pelvis

A dermold cyst, arising from the posterior aspects of the prostate and seminal vesicles, and extending into the pelvis to masquerade as a full bladder, must be exceedingly rare. Ultrasound, computed tomography and especially magnetic resonance imaging (MRI) proved to be invaluable in making the diagnosis, and MRI in particular was very useful in providing an anatomical road map for surgery.     

Clinical Profile and Outcome of Aluminum Phosphide-Induced Esophageal Strictures

Aluminum phosphide (AlP) is a lethal solid fumigant pesticide which has been recently linked to esophageal stricture formation. This paper aims to study the clinical profile and response to treatment of AlP-induced esophageal strictures. Data on all patients of AlP-induced strictures seen between January 2004 and June 2008 were retrieved and analyzed for clinical parameters and response to endoscopic dilation. Each patient underwent barium swallow to define the site and length of stricture and then was dilated endoscopically. Twelve patients of AlP-induced esophageal stricture (seven males) with a mean age of 26.83?±?8.43 years were evaluated. They had consumed one to three AlP tablets, 4–156 weeks before reporting to us. They had onset of dysphagia within 2 to 8 weeks of ingestion of AlP. Of 14 strictures in 12 patients, seven were in upper third, two in middle third, and five in lower third of esophagus with a mean length of 1.96?±?0.75 cm. Nine patients responded to dilation requiring 5.56?±?2.65 dilations. Four patients were given intralesional steroids to augment the effect of dilation. Three patients failed and were operated upon. All patients remained symptom free over a follow-up of 3–30 (15.67?±?9.41)?months. AlP-induced esophageal strictures can be dilated endoscopically in a majority of patients; however, 25% of them require surgical intervention. AlP-induced esophageal strictures, thus, behave like caustic-induced strictures.     

A combination of misoprostol and estradiol for preoperative cervical ripening in postmenopausal women: a randomised controlled trial

Objective  To compare the impact of 1000 μg of self-administered vaginal misoprostol versus self-administered vaginal placebo on preoperative cervical ripening after 2 weeks of pretreatment with estradiol vaginal tablets in postmenopausal women prior to day-care operative hysteroscopy.
Design  Randomised, double-blind, placebo-controlled sequential trial.
Setting  Norwegian university teaching hospital.
Population  Sixty-seven postmenopausal women referred for day-care operative hysteroscopy.
Methods  The women were randomised to receive either 1000 μg of self-administered vaginal misoprostol or self-administered vaginal placebo on the evening before day-care operative hysteroscopy. All women had administered a 25-μg vaginal estradiol tablet daily for 14 days prior to the operation.
Main outcome measures  Primary outcome: preoperative cervical dilatation at hysteroscopy. Secondary outcomes: difference in dilatation at recruitment and before hysteroscopy, number of women who achieved a preoperative cervical dilatation of 5 mm or more, acceptability, complications and adverse effects.
Results  The mean cervical dilatation was 5.7 mm (SD, 1.6 mm) in the misoprostol group and 4.7 mm (SD, 1.5 mm) in the placebo group, the mean difference in cervical dilatation being 1.0 mm (95% CI, 0.2–1.7 mm). Self-administered vaginal misoprostol of 1000 μg at home on the evening before day-care hysteroscopy is safe and highly acceptable, although a small proportion of women experienced lower abdominal pain.
Conclusions  One thousand micrograms of self-administered vaginal misoprostol, 12 hours prior to day-care hysteroscopy, after 14 days of pretreatment with vaginal estradiol, has a significant cervical ripening effect compared with placebo in postmenopausal women.     

转录因子T-bet与哮喘大鼠气道炎症及川芎嗪的干预效应

目的:转录因子T-bet在支气管哮喘的发病中起重要作用,川芎嗪治疗哮喘有效。实验拟观察川芎嗪对哮喘大鼠气道炎症的影响和转录因子T-bet的调控作用。方法:实验于2005-11/2006-06在南京医科大学完成。①实验材料及分组:72只SPF级SD大鼠随机分为正常对照组、哮喘模型组、川芎嗪小剂量组(20mg/kg)、川芎嗪中剂量组(40mg/kg)、川芎嗪大剂量组(80mg/kg)和地塞米松组,每组12只。实验用磷酸川芎嗪注射液为丽珠集团利民制药厂生产)。②实验过程及评估:以卵蛋白腹腔注射并雾化吸入制备大鼠哮喘模型,末次雾化后24h内麻醉后处死大鼠。观察6组大鼠肺组织形态学变化;测定支气管壁厚度、支气管平滑肌厚度、嗜酸粒细胞和淋巴细胞数。采用免疫组织化学半定量法测定肺组织T-bet蛋白的表达;进行转录因子T-bet蛋白表达量与气道炎症的相关性分析。实验过程中对动物处置符合动物伦理学标准。结果:①哮喘模型组嗜酸粒细胞、淋巴细胞、支气管壁厚度和支气管平滑肌厚度,明显高于正常对照组相应指标(P均<0.01);与哮喘模型组比较,川芎嗪小、中、大剂量组和地塞米松组上述4项指标均减少(P均<0.01)。②哮喘模型组、川芎嗪小、中、大剂量组和地塞米松组的T-bet表达量低于正常对照组(P均<0.01);与哮喘模型组比较,川芎嗪小、中、大剂量组T-bet表达量增加(P均<0.01);随着川芎嗪剂量增加,T-bet表达量亦相应增加,川芎嗪小、中、大剂量组之间两两比较,差异均有统计学意义(P均<0.01)。③相关分析显示哮喘模型组T-bet蛋白表达量与嗜酸性粒细胞和淋巴细胞浸润数呈负相关(r=-0.81,-0.85,P<0.01),与支气管管壁厚度和支气管平滑肌厚度呈负相关(r=-0.77,-0.79,P<0.01)。结论:支气管哮喘大鼠存在T-bet低表达;川芎嗪可抑制气道炎症,增加转录因子T-bet蛋白的表达,纠正Th1/Th2失衡,从而治疗支气管哮喘。     

Hydrogen peroxide inhibits gap junctional intercellular communication in glutathione sufficient but not glutathione deficient cells

Cell to cell communication via gap junctions is essential in the maintenance of the homeostatic balance of multicellular organisms. Aberrant intercellular gap junctional communication (GJIC) has been implicated in tumor promotion, neuropathy and teratogenesis. Oxidative stress has also been implicated in similar pathologies such as cancer. We report a potential link between oxidative stress and GJIC. Hydrogen peroxide, a known tumor promoter, inhibited GJIC in WB-F344 rat liver epithelial cells with an I50 value of 200 microM. Inhibition of GJIC by H2O2 was reversible as indicated by the complete recovery of GJIC with the removal of H2O2 via a change of fresh media. Free radical scavengers, such as t-butyl alcohol, propylgallate, and Trolox, did not prevent the inhibition of GJIC by H2O2, which indicated that the effects of H2O2 on GJIC was probably not a consequence of aqueous free radical damage. The depletion of intracellular GSH reversed the inhibitory effect of H2O2 on GJIC. The treatment of glutathione- sufficient cells with H2O2 resulted in the hyperphosphorylation of connexin43, which is the basic subunit of the hexameric gap junction protein, as determined by Western blot analysis. TPA, a well-known tumor promoter, also inhibits GJIC via hyperphosphorylation of GJIC, which is a result of protein kinase-C activation. However, H2O2 also induced hyperphosphorylation in GSH-deficient cells that had normal rates of GJIC. Therefore, the mechanism of GJIC inhibition must be different from the TPA-pathway and involves GSH.      

A crucial role for TNF-α in mediating neutrophil influx induced by endogenously generated or exogenous chemokines,KC/CXCL1 and LIX/CXCL5

Background and purpose:

Chemokines orchestrate neutrophil recruitment to inflammatory foci. In the present study, we evaluated the participation of three chemokines, KC/CXCL1, MIP-2/CXCL2 and LIX/CXCL5, which are ligands for chemokine receptor 2 (CXCR2), in mediating neutrophil recruitment in immune inflammation induced by antigen in immunized mice.

Experimental approach:

Neutrophil recruitment was assessed in immunized mice challenged with methylated bovine serum albumin, KC/CXCL1, LIX/CXCL5 or tumour necrosis factor (TNF)-α. Cytokine and chemokine levels were determined in peritoneal exudates and in supernatants of macrophages and mast cells by elisa. CXCR2 and intercellular adhesion molecule 1 (ICAM-1) expression was determined using immunohistochemistry and confocal microscopy.

Key results:

Antigen challenge induced dose- and time-dependent neutrophil recruitment and production of KC/CXCL1, LIX/CXCL5 and TNF-α, but not MIP-2/CXCL2, in peritoneal exudates. Neutrophil recruitment was inhibited by treatment with reparixin (CXCR1/2 antagonist), anti-KC/CXCL1, anti-LIX/CXCL5 or anti-TNF-α antibodies and in tumour necrosis factor receptor 1-deficient mice. Intraperitoneal injection of KC/CXCL1 and LIX/CXCL5 induced dose- and time-dependent neutrophil recruitment and TNF-α production, which were inhibited by reparixin or anti-TNF-α treatment. Macrophages and mast cells expressed CXCR2 receptors. Increased macrophage numbers enhanced, while cromolyn sodium (mast cell stabilizer) diminished, LIX/CXCL5-induced neutrophil recruitment. Macrophages and mast cells from immunized mice produced TNF-α upon LIX/CXCL5 stimulation. Methylated bovine serum albumin induced expression of ICAM-1 on mesenteric vascular endothelium, which was inhibited by anti-TNF-α or anti-LIX/CXCL5.

Conclusion and implications:

Following antigen challenge, CXCR2 ligands are produced and act on macrophages and mast cells triggering the production of TNF-α, which synergistically contribute to neutrophil recruitment through induction of the expression of ICAM-1.