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SM Vieira HP Lemos R Grespan MH Napimoga D Dal-Secco A Freitas TM Cunha WA Verri Jr DA Souza-Junior MC Jamur KS Fernandes C Oliver JS Silva MM Teixeira FQ Cunha 《British journal of pharmacology》2009,158(3):779-789
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. 相似文献64.
Iriemenam NC Khirelsied AH Nasr A ElGhazali G Giha HA Elhassan A-Elgadir TM Agab-Aldour AA Montgomery SM Anders RF Theisen M Troye-Blomberg M Elbashir MI Berzins K 《Vaccine》2009,27(1):62-71
Despite many intervention programmes aimed at curtailing the scourge, malaria remains a formidable problem of human health. Immunity to asexual blood-stage of Plasmodium falciparum malaria is thought to be associated with protective antibodies of certain immunoglobulin classes and subclasses. We have analysed immunoglobulin G profiles to six leading blood-stage antigens in relation to clinical malaria outcome in a hospital-based study in Sudan. Our results revealed a linear association with anti-AMA-1-IgG1 antibodies in children <5 years and reduced risk of severe malaria, while the responses of the IgG3 antibodies against MSP-2, MSP-3, GLURP in individuals above 5 years were bi-modal. A dominance of IgG3 antibodies in >5 years was also observed. In the final combined model, the highest levels of IgG1 antibodies to AMA-1, GLURP-R0, and the highest levels of IgG3 antibodies to 3D7 MSP-2 were independently associated with protection from clinical malaria. The study provides further support for the potential importance of the studied merozoite vaccine candidate antigens as targets for parasite neutralizing antibody responses of the IgG1 and IgG3 subclasses. 相似文献
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Background Negative surgical margins minimize the risk of local recurrence after breast-conserving surgery. Intraoperative frozen section
analysis (FSA) is one method for margin evaluation. We retrospectively analyzed records of patients who received breast-conserving
therapy with intraoperative FSA of the lumpectomy cavity to assess re-excision rates and local control.
Methods Records were retrospectively reviewed for individuals who underwent breast-conserving surgery for ductal carcinoma in situ
(DCIS) or invasive carcinoma between 1993 and 2003. Inclusion criteria were a minimum of 2 years follow-up and intact tumor
at the time of operation. The major outcome measure was local recurrence. The Kaplan-Meier test was used to evaluate local
recurrence rates between groups.
Results 290 subjects with an average age of 57.2 years (range 27–89) underwent 292 lumpectomies with FSA. 11.3% had DCIS, 73.3% had
infiltrating ductal, 5.8% had infiltrating lobular, and 9.6% exhibited other forms of invasive carcinoma. 70 subjects underwent
additional resection at the time of breast surgery, 16 underwent subsequent re-excision, and 17 underwent subsequent mastectomy.
At a median follow-up of 53.4 months (range 5.8–137.8), there were six local recurrences (2.74%) in patients who had breast-conserving
procedures and two local recurrences in patients who underwent mastectomy. There were no statistically significant associations
among local recurrence rate, tumor size, nodal status, or overall stage. Local recurrences were higher in patients with DCIS
compared with invasive carcinoma, and tumors >2cm.
Conclusions Intraoperative FSA allows resection of suspicious or positive margins at the time of lumpectomy and results in low rates of
local recurrence and re-excision. The low local recurrence rate reported here is comparable to those reported with other margin
assessment techniques. 相似文献
67.
一阶导数差示脉冲极谱法的建立及在药物分析中的应用 总被引:11,自引:0,他引:11
本文研究了一阶导数差示脉冲极谱法,并将其运用于扑尔敏、氟哌啶醇、维生素B6及其制剂的定量分析中。方法简便、快速、灵敏、结果准确。 相似文献
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A randomized prospective comparison of oral versus intraperitoneal ofloxacin as the primary treatment of CAPD peritonitis 总被引:1,自引:0,他引:1
Ignatius KP CHENG SL LUI GX FANG PY CHAU SW CHENG Frances H CHIU TM CHAN WK LO BY CHOY CY LO 《Nephrology (Carlton, Vic.)》1997,3(6):431-435
Summary: Oral ofloxacin has been successfully used in our centres for the primary treatment of peritonitis complicating continous ambulatory peritoneal dialysis (CAPD). In view of the progressive rise in the resistance rate to ofloxacin among peritoneal bacterial isolates, a study was conducted to determine if oral ofloxacin remains a viable first line treatment for CAPD peritonitis in our centres and if the result can be improved by changing from an oral to an intraperitoneal (i.p.) route. In patients on three 2 L daily CAPD exchanges, ofloxacin given at the i.p. dosage of 200 mg loading followed by 25 mg/L of peritoneal dialysate achieved overnight trough peritoneal levels which are at least four times the minimal 90% inhibitory concentration (MIC90) of most bacterial pathogens without significant accumulation in the systemic circulation. This i.p. dosage was therefore chosen for the clinical study and the result was compared to that using ofloxacin given in the oral dosage of 400 mg loading followed by 300 mg once daily as maintenance. of all the recruited episodes, 35 were eligible for analysis. the overall primary cure rate including primary failures and relapses was 55.6% (10/18) in the oral treatment group and 70.6% (12/17) in the i.p. treatment group. the corresponding figures for gram positive bacterial (g +) infections were 36.4% and 50%, for gram negative bacterial (g -) infections were 66.7 and 80% and for culture negative infections were 75 and 80%. In culture positive cases, all treatment failures were due to resistant infections which were observed in 42.3% of all bacterial isolates, 47.1% of g + isolates and 33.3% of g - isolates. Due to the high background level of bacterial resistance among our CAPD population, ofloxacin monotherapy given either by the oral or the i.p. route can no longer be recommended for the primary treatment of CAPD peritonitis. 相似文献