Probiotic-induced suppression of allergic sensitization and airway inflammation is associated with an increase of T regulatory-dependent mechanisms in a murine model of asthma

BACKGROUND: Microbial intestinal colonization in early in life is regarded to play a major role for the maturation of the immune system. Application of non-pathogenic probiotic bacteria during early infancy might protect from allergic disorders but underlying mechanisms have not been analysed so far. OBJECTIVE: The aim of the current study was to investigate the immune effects of oral application of probiotic bacteria on allergen-induced sensitization and development of airway inflammation and airway hyper-reactivity, cardinal features of bronchial asthma. METHODS: Newborn Balb/c mice received orally 10(9) CFU every second day either Lactobacillus rhamnosus GG or Bifidobacterium lactis (Bb-12) starting from birth for consecutive 8 weeks, during systemic sensitization (six intraperitoneal injections, days 29-40) and airway challenge (days 54-56) with ovalbumin. RESULTS: The administration of either Bb-12 or LGG suppressed all aspects of the asthmatic phenotype: airway reactivity, antigen-specific immunoglobulin E production and pulmonary eosinophilia (mean: 137 vs. 17 and 13 cellsx10(3)/mL, respectively). Antigen-specific recall proliferation by spleen cells and T-helper type 2 cytokine production (IL-4, IL-5 and IL-10) by mesenteric lymph node cells also showed significant reduction, while TGF production remained unchanged. Oral LGG administration particularly suppressed allergen-induced proliferative responses and was associated with an increase in numbers of TGF-beta-secreting CD4+/CD3+ T cells in mesenteric lymph nodes (6.5, 16.7%) as well as nearly 2-fold up-regulation of Foxp3-expressing cells in peribronchial lymph nodes. CONCLUSIONS: Neonatal application of probiotic bacteria inhibits subsequent allergic sensitization and airway disease in a murine model of asthma by induction of T regulatory cells associated with increased TGF-beta production.     

干部门诊就诊质量的影响因素与对策

对900例干部门诊中的就诊患者进行问卷调查分析,探讨干部门诊就诊质量的各种影响因素,提出干预措施,在提高患者就诊质量的前提下节省卫生资源.     

铁调节蛋白2基因多态性与阿尔茨海默病及血管性痴呆的相关分析

Objective To evaluate the association of 2616c/T polymorphism in iron regulatory protein 2(IRP2)gene with Alzheimer disease(AD)and Vascular dementia(VD).Methods In this study,281 patients with AD,60 with VD,and 285 normal aged were recruited.The 2616C/T polymorphism in IRP2 gene was analyzed by using polymerase chain reaction-restriction fragment length polymorphism.And the cognitive function was assessed with the Mini-Mental State Examination(MMSE).Results (1)No significant difieFences were demonstrated in IRP2 genotype or allele frequencies between AD patients and controls(χ2=2.46,P=0.292;χ2=2.17,P=0.141 respectively).However,when AD patients were stratified by disease severity.the frequency of T allele carriers in the moderate to severe AD patients was 78.0%,significantly higher than that in controls(69.8%;χ2=4.106,P＜0.05).Logistic regression analysis demonstrated that the age-,sex-and ApoE-adiusted OR of modcrate to severe AD patient with T allele was 1.62(95% CI=1.03-2.54).The frequency of T allele carriers or T allele in VD patients was higher than that of controls,but the difference was not statistically significant(P＞0.05).(2)The frequency of tit genotype or T allele in the moderate to severe AD patients was significantly higher than that in mild AD patients(25.8%vs.12.5%,χ2=5.477,P＜0.05;51.9%vs.40.3%,χ2=5.803,P＜0.05 respectively).(3)MMSE scores of the AD patients with TT genotype was significantly lower than ones with CC or CT genotype(P=0.028;P=0.014 respectively).Conclusion The 2616C/T polymorphism in the IRP2 gene is possibly associated with moderate to severe AD.but not associated with VD.And the TT genotype may be a risk factor for cognitive impairment of patients with AD in Chinese Han.     

The Van der Woude syndrome: a case report and review of the literature

The Van der Woude syndrome is a rare autosomal dominant developmental malformation usually associated with bilateral lower lip pits. These congenital lip pits appear clinically as a malformation in the vermilion border of the lip, with or without excretion. As a genetic defect has been identified as a microdeletion of chromosome bands 1q32-q41, genetic counselling of patients may be considered. A nonsense mutation in the interferon regulatory factor-6 (IRF-6) is discussed as a pathogenic relevant factor. Therapeutic intervention is generally not necessary, although surgical excision is especially indicated in patients with recurrent inflammation. Physicians should be aware of the Van der Woude syndrome because it has been reported to be associated with a variety of malformations or other congenital disorders.     

Phenotypic and genetic analyses of T-cell-mediated immunoregulation in patients with Type 1 diabetes.

AIMS: To investigate the contribution of regulatory T cells and co-stimulatory molecules in CD4(+) T cells to the development of Type 1 diabetes (T1D). METHODS: Twelve patients with T1D, nine patients with systemic lupus erythematosus (SLE), and 12 age-matched healthy control subjects participated. We analysed the proportions of CD25(+)CD4(+) T cells and natural killer T cells (NKT cells), and the expression levels of Foxp3, CTLA-4, CD28, ICOS, PD-1 and BTLA in peripheral blood mononuclear cells and purified CD4(+) T cells. RESULTS: There were no significant differences in the proportions of CD25(+) CD4(+) T cells or NKT cells among the three groups. PD-1 expression levels of peripheral CD4(+) T cells from T1D patients were significantly lower than those from healthy control subjects (P = 0.00066). In contrast, PD-1 expression levels were similar in SLE patients and healthy control subjects. The expression levels of Foxp3, CTLA-4, CD28, ICOS and BTLA were similar in the three groups. CONCLUSIONS: Decreased expression of the PD-1 gene in CD4(+) T cells may contribute to the development and/or maintenance of autoimmune T1D. As the population studied was small and heterogeneous, further studies are required to confirm the findings.     

Intranasal treatment with ovalbumin but not the major T cell epitope ovalbumin 323–339 generates interleukin-10 secreting T cells and results in the induction of allergen systemic tolerance

BACKGROUND: Nasal administration of major peptide T cell epitopes gives contradictory data on the induction of peripheral tolerance. OBJECTIVE: To compare the prophylactic effect of intranasal treatment (INT) on the development of an allergic response, using either ovalbumin (OVA) or its major T cell epitope OVA 323-339 (OVAp). METHODS: BALB/c mice were treated intranasally with OVA or OVAp and subsequently immunized s.c. with OVA. Anti-OVA-specific antibody, T cell proliferation and cytokine responses were analysed. In an adoptive transfer model using OVAp specific TCR transgenic (Tg) T cells from D011.10 mice, in vivo tracking and characterization of transferred T cells in the cervical, inguinal and bronchial lymph nodes (BLN) and in the spleen were determined by FACS analysis. RESULTS: Prophylactic INT with OVA induced T cell tolerance towards subsequent OVA s.c. immunizations, inhibiting OVA specific T cell proliferation, IgE and IgG1 production, in contrast to INT with OVAp, which was unable to induce tolerance. In vivo analysis of transferred OVA-specific TCR Tg T cells showed that INT with OVA induced a preferential activation of T cells in BLN, as opposed to a broad, systemic activation with OVAp. In vivo, OVAp INT led to faster and more sustained cell division cycles than OVA INT. Ex vivo, tolerance to OVA was associated with the generation of IL-10 secreting CD4(+) T cells in BLN of OVA-treated mice only. CONCLUSION: INT with OVA but not with OVAp led to regional (as opposed to systemic) T cell activation and the induction of IL-10 secreting CD4(+) T cells in BLN, potentially critical steps in the induction of T cell-specific tolerance via the nasal route.     

对药品市场营销中代理环节监督管理的思考

随着我国药品分销市场的对外放开,传统的批发零售经营方式发生了根本变化,代理配送制将成为医药流通的主要方式.药监工作人员要准确掌握药品分销市场的现状及发展趋势,抓好药品市场营销中代理环节的监督管理.     

Following Anti-CD25 Treatment, A Functional CD4+CD25+ Regulatory T-Cell Pool Is Present in Renal Transplant Recipients

Daclizumab, a humanized antibody directed against the alpha-chain of the interleukin-2 receptor (CD25), has shown efficacy in the prevention of acute rejection following organ transplantation. However, anti-CD25 therapy can be expected to affect not only alloreactive effector T cells, but also CD4(+)CD25(+) regulatory T (Treg) cells that are shown to play an important role in the induction of transplantation tolerance. Therefore, the size and function of the Treg pool in human renal allograft recipients after single-dose daclizumab administration was investigated in this study. Approximately 8 weeks after administration, daclizumab was cleared from the circulation and the Treg population then present appeared not different from that observed before transplantation. Functional analysis revealed that the Treg possessed a normal capacity to suppress mixed lymphocyte reactions in vitro. These data indicate that after daclizumab therapy a Treg population, normal in number and function, is present in the peripheral blood of renal transplant recipients.