Effect of exercise on the reproductive outcome and fetal development of diabetic rats

The aim of this study was to evaluate the effect of exercise on pregnancy outcome in streptozotocin-induced diabetic Wistar rats (n = 11 animals/group). These animals were randomly assigned to sedentary (G1) and exercised groups, beginning from day 0 (G2) or 7 (G3) to day 20 of pregnancy. The moderate exercise was a swimming programme. At day 21 of pregnancy, all rats were anaesthetized and killed to obtain pregnancy outcome data. All rats presented glycaemia higher than 300 mg/dl, regardless of the exercise training. The G3 group showed higher live fetus number per implantation site and lower resorption number per implantation site compared with the G1 group. The fetal and placental mean weights per litter and the total number of ossification sites were significantly lower in the exercised groups (P < 0.05). Placental index was lower in the G2 and G3 groups compared with the G1 group. The occurrence of skeletal anomalies indicated that exercise increased the number of altered fetuses. Thus, moderate exercise achieved better outcomes by increasing the number of live births and decreasing resorption. However, exercise increased skeletal anomalies and decreased fetal and placental weights.     

Pneumococcal vaccine efficacy for mucosal pneumococcal infections depends on Fcgamma receptor IIa polymorphism

IgG2 antibodies are the main antibody subclass produced after pneumococcal polysaccharide vaccination. For these antibodies to be effective, interaction with FcgammaIIa receptors on phagocytic cells is necessary. FcgammaRIIa displays a functional polymorphism with either a histidine (H) or arginine (R) at position 131. Interaction of IgG2 antibodies depends on the H131 allele, whereas this interaction is low to absent with the R131 allele. We tested the clinical efficacy of combined pneumococcal conjugate and pneumococcal polysaccharide vaccination according to FcgammaIIa-H/R131 genotype in a randomized double blind placebo controlled vaccination trial in children with a history of acute otitis media. We found a decisive role for the FcgammaIIa-H/R131 polymorphism on the clinical vaccine efficacy of combined pneumococcal conjugate and polysaccharide vaccinations. RR homozygotes showed a significant increase in recurrence of acute otitis media after pneumococcal vaccinations. This cannot be explained by differences in the pneumococcal specific antibody response or differences in nasopharyngeal pneumococcal carriage, but may be explained by less efficient interaction of FcgammaRIIa with polysaccharide-induced IgG2 anti-pneumococcal antibodies in RR homozygotes. Our data show that the genetic make-up of individuals or populations under study should be considered while evaluating vaccine efficacy trials.     

Lack of isoprenoid products raises ex vivo interleukin-1beta secretion in hyperimmunoglobulinemia D and periodic fever syndrome

OBJECTIVE: To investigate whether the increased interleukin-1beta (IL-1beta) secretion in hyperimmunoglobulinemia D and periodic fever syndrome is due to the accumulation of mevalonate kinase (MK), the substrate of the deficient enzyme, or the lack of its products, the isoprenoid compounds. METHODS: The effects of lovastatin and farnesol (FOH), geranylgeraniol (GGOH), and mevalonate on peripheral blood mononuclear cells (PBMCs) from 8 patients with MK deficiency and from 13 controls were studied. Lovastatin inhibits isoprenoid biosynthesis by reducing the production of mevalonate. FOH and GGOH restore isoprenoid biosynthesis downstream from MK. Culture supernatants were collected for cytokine analysis 48 hours after stimulation with monoclonal antibodies against CD2 + CD28. RESULTS: Lovastatin induced a 15-fold rise in IL-1beta secretion by normal anti-CD2 + CD28-stimulated cells (P < 0.001). This effect could be countered by mevalonate and, to a lesser extent, by FOH and GGOH. In the absence of lovastatin, mevalonate did not change IL-1beta secretion. Stimulated MK-deficient cells secreted 9-fold more IL-1beta than control PBMCs (P < 0.005), rising 2.4-fold in the presence of lovastatin. The effect of lovastatin on IL-1beta secretion was reduced by mevalonate, FOH, and GGOH. Isoprenoid biosynthesis in PBMCs from patients was impaired due to the endogenous MK deficiency. Bypassing this defect with FOH, in the absence of lovastatin, led to a 62% reduction (P < 0.02) in IL-1beta secretion by these cells. CONCLUSION: In this model, shortage of isoprenoid end products contributes to increased IL-1beta secretion by MK-deficient PBMCs, whereas excess mevalonate does not.     

(-)-Epigallocatechin-3-gallate inhibition of ultraviolet B-induced AP-1 activity

Green tea polyphenols have been shown to inhibit cancer in a variety of tumor models, including ultraviolet B (UVB)-induced non-melanoma skin cancer. In green tea extracts, the major dry mass constituent is the family of catechins, of which (-)-epigallocatechin-(3)-gallate (EGCG) is considered to be important for the chemopreventive activity. EGCG has been shown to have antioxidant properties, but there has been little progress toward identifying the specific targets and mechanisms of its action. Using cultured human keratinocytes, we show that UVB- induced AP-1 activity is inhibited by EGCG in a dose range of 5.45 nM to 54.5 microM. EGCG is effective at inhibiting AP-1 activity when applied before, after or both before and after UVB irradiation. EGCG also inhibits AP-1 activity in the epidermis of a transgenic mouse model. This work begins to define a mechanism by which EGCG could be acting to inhibit UVB-induced tumor formation.      

Phenotypical and functional analysis of B lymphocytes of two siblings with combined immunodeficiency and defective expression of major histocompatibility complex (MHC) class II antigens on mononuclear cells

Phenotypic and functional analysis of B lymphocytes in two siblings with combined immunodeficiency associated with defective expression of class I and class II major histocompatibility complex (MHC) antigens on mononuclear cells is described. The results of the analysis of the membrane phenotype of the B cells performed at the age of 1 and 5 years, respectively, by the use of monoclonal antibodies against class I (HLA-A, -B, -C) and class II (HLA-DR, -DP, -DQ) MHC antigens showed a decreased expression of class I antigens and a complete lack of class II antigens. Class I antigen expression consistently remained of the same magnitude during follow-up. Class II antigen expression remarkably had been positive early in life on B cells and activated T cells, whereas monocytes were negative for class II from birth onward. B lymphocytes of both patients respondedin vitro to polyclonal activation withStaphylococcus aureus Cowan I staphylococci (SAC) with the production of IgM-type immunoglobulins only. This neonatal type of response was in agreement with the membrane immunoglobulin phenotype of the B cells since a high sIgM/sIgD ratio characteristic of neonatal B cells was present. However, the expression of the FMC7 antigen on B cells of both patients was comparable to that on B cells of normal adults. We hypothesized that the lack of MHC antigen expression may impose a resting state on the lymphocytes in these patients due to ineffective cellular interactions. In this view the high sIgM/sIgD ratio reflects the activation state of the B cells rather than the maturational state of the cells. Furthermore, the B cells of these patients did not produce antipolysaccharide antibodies upon simultaneous stimulation with SAC and pokeweed mitogen (PWM). In the youngest child (age 1 year) this may reflect the unresponsiveness to polysaccharide antigens usually observed in children less than 2 years old. In the eldest child the nonresponsiveness might reflect a more general B-cell defect as a result of waning B-cell function increasing with age and imposed by lack of effectivein vivo activation.     

Comparison of the anti-inflammatory effects of extra-fine hydrofluoroalkane-beclomethasone vs fluticasone dry powder inhaler on exhaled inflammatory markers in childhood asthma.

BACKGROUND: Extra-fine hydrofluoroalkane-beclomethasone differs from other inhaled corticosteroids by its fine aerosol characteristics. Therefore, extra-fine hydrofluoroalkane-beclomethasone may be particularly useful for treating peripheral airway inflammation in asthma. OBJECTIVE: To analyze the anti-inflammatory effects of extra-fine hydrofluoroalkane-beclomethasone vs fluticasone dry powder inhaler (DPI) in asthmatic children by measuring bronchial and alveolar nitric oxide (NO) and inflammatory markers in exhaled breath condensate (EBC). METHODS: In a 6-month crossover study, 33 children aged 6 to 12 years with moderate persistent asthma were randomly treated with extra-fine hydrofluoroalkane-beclomethasone (200 microg daily via an Autohaler) and fluticasone DPI (200 microg daily via a Diskus). The primary outcome variables were alveolar NO concentration and bronchial NO flux. The secondary outcome variables were levels of inflammatory markers in EBC, lung function indices, symptoms, exacerbations, and adverse effects. All the variables were recorded at baseline and after each treatment period. RESULTS: Mean +/- SE alveolar NO concentration and bronchial NO flux were comparable after treatment with hydrofluoroalkane-beclomethasone vs fluticasone DPI (4.7 +/- 0.5 vs 4.3 +/- 0.5 ppb, P = .55, and 1,124.3 +/- 253.6 vs 1,029.1 +/- 195.5 pL/s, P = .70, respectively). In addition, levels of inflammatory markers in EBC, lung function indices, and symptoms did not differ between treatments. Patients used fewer beta2-agonists during the last 2 weeks of hydrofluoroalkane-beclomethasone treatment. CONCLUSION: The anti-inflammatory effects of hydrofluoroalkane-beclomethasone are similar to those of fluticasone DPI in children with moderate persistent asthma.     

The spontaneous remission of juvenile idiopathic arthritis is characterized by CD30+ T cells directed to human heat‐shock protein 60 capable of producing the regulatory cytokine interleukin‐10

Objective

To test the hypothesis that T cell reactivity to self heat‐shock protein 60 (Hsp60) in patients with remitting juvenile idiopathic arthritis (JIA) is part of an antiinflammatory, regulatory mechanism.

Methods

Using peripheral blood–derived mononuclear cells (PBMCs) and synovial fluid–derived mononuclear cells (SFMCs) obtained from patients with JIA, we analyzed the expression of CD30 and the induction of regulatory cytokines in response to human and mycobacterial Hsp60.

Results

In oligoarticular JIA patients, in vitro activation of PBMCs and SFMCs with Hsp60 induced a high expression of CD30 on CD4+, activated (HLA–DR–positive), memory (CD45RO+) T cells. The expression of CD30 induced by human Hsp60 was much higher than that induced by mycobacterial Hsp60. In oligoarticular JIA patients with active disease, the expression of CD30 in response to human Hsp60 was paralleled by a high interleukin‐10 (IL‐10):interferon‐γ (IFNγ) ratio. In addition, restimulated human Hsp60–specific T cell lines from oligoarticular JIA patients showed a high production of IL‐10 and a low production of IFNγ. In contrast, PBMCs and SFMCs from polyarticular JIA patients responded to human Hsp60 with virtually no expression of CD30 and a low IL‐10:IFNγ ratio.

Conclusion

The results show that T cells responding to human Hsp60 in oligoarticular JIA patients express CD30, and during active phases of the disease, these T cells have a cytokine profile with a high IL‐10:IFNγ ratio. These findings suggest that in oligoarticular JIA patients, human Hsp60–specific CD4+ cells have a regulatory function and contribute to disease remission.

     

去甲斑蝥酸钠白蛋白微球的研究

选择去甲斑蝥酸钠为模型药物,对含药白蛋白微球的制备、载药性能、形态、表面状态、大小及分布、体外释药、冷冻干燥、⁶⁰Co辐照灭菌和稳定性等进行了研究。结果表明,去甲斑蝥酸钠微球的平均大小为0.43±0.12μm,药物含量为20.34～26.75μg/ml,包入率21.9～26.4%,体外释药符合Higuchi方程,冷冻干燥和⁶⁰Co辐照对微球无影响且能达到无菌要求,放置3个月后微球的稳定性良好。     

Evidence that FMC7 is a human B cell differentiation antigen.

FMC7 is a 105-kDa B cell restricted antigen which is expressed on about 50% of adult human peripheral blood B cells. Seven to ten days following booster immunization with tetanus toxoid, peripheral blood contains a small population of B cell blasts with an increased density of FMC7. The majority of anti-tetanus toxoid antibody secreting cells (both IgM and IgG) are however found in FMC7- B cells. These data indicate that upon in vivo B cell activation FMC7 expression initially increases. B cells involved in antibody secretion have lost the FMC7 determinant.