No abstract

Maternal age at first childbirth has increased in most developed countries in the past 20 years. The purpose of this study is to investigate effects of maternal age at delivery and parity on successful initiation of exclusive breastfeeding (EBF). This retrospective study investigated 1193 singleton dyads with vaginal-delivered at 37–42 gestational weeks during January and December in 2011 at one large “Baby-Friendly” certified hospital in Japan. A multivariate logistic regression model was used to evaluate individual and combined effects of maternal age and parity on successful initiation of EBF after adjusted for pre-pregnancy body mass index, gestational weight gain, pregnancy complications, mothers' underlying illness, smoking and alcohol drinking habits, gestational week at delivery, child's sex and nurturing support from grandparents. Success rates of EBF at one month after child delivery was 69.4% in primiparous aged ≥ 35 (group A: n = 284), 73.5% in multiparous aged ≥ 35 (group B: n = 268), 74.3% in primiparous aged < 35 (group C: n = 432), and 82.3% in multiparous aged < 35 (group D: n = 209). Older maternal age and primiparous became independently associated with EBF initiation. The combined effect for successful initiation of EBF was the lowest in group A referent to group D both at discharge and at one month (odds ratio (OR) 5.9, 95% confidence interval (CI): 3.0–11.9, and OR 2.2, 95% CI: 1.4–3.4, respectively). Primiparous mothers in late child-bearing aged 35 years or older are at the greatest risk of EBF initiation.

The gut microbiota were shown to play critical roles in the development of atherosclerosis, but the detailed mechanism is limited. The purpose of this study is to clarify the influence of gut microbiota on atherogenesis via lipid metabolism and systemic inflammation. Germ-free or conventionally raised (Conv) ApoE-deficient (ApoE−/−) mice were fed chow diet and euthanized at 20 weeks of age. We found that the lack of gut microbiota in ApoE−/− mice caused a significant increase in the plasma and hepatic cholesterol levels compared with Conv ApoE−/− mice. The absence of gut microbiota changed the bile acid composition in the ileum, which was associated with activation of the enterohepatic fibroblast growth factor 15, fibroblast growth factor receptor 4 axis, and reduction of cholesterol 7α-hydroxylase and hepatic bile acid synthesis, resulting in the accumulation of liver cholesterol content. However, we found that the lack of microbiota caused a significant reduction in atherosclerotic lesion formation compared with Conv ApoE−/− mice, which might be associated with the attenuation of lipopolysaccharide-mediated inflammatory responses. Our findings indicated that the gut microbiota affected both hypercholesterolemia and atherogenesis in mice.

BackgroundMetabolic syndrome has become a major worldwide public health problem. We examined the relationship between coffee consumption and the prevalence of metabolic syndrome among Japanese civil servants.MethodsThe study participants were 3284 employees (2335 men and 948 women) aged 20 to 65 years. Using data from their 2008 health checkup records, we analyzed the relationship between coffee consumption and the prevalence of metabolic syndrome. Metabolic syndrome was defined according to the Japanese criteria.ResultsMetabolic syndrome was diagnosed in 374 of the 2335 men (16.0%) and 32 of the 948 women (3.4%). In univariate and multiple logistic regression analyses, the odds ratios (ORs) among men for the presence of metabolic syndrome were 0.79 (95% CI: 0.56–1.03) and 0.61 (0.39–0.95), respectively, among moderate (≥4 cups of coffee per day) coffee drinkers as compared with non-coffee drinkers. Among all components of metabolic syndrome, high blood pressure and high triglyceride level were inversely associated with moderate coffee consumption in men, after adjusting for age, body mass index, smoking status, drinking status, and exercise. However, in women, moderate coffee consumption was not significantly associated with the prevalence of metabolic syndrome or its components.ConclusionsModerate coffee consumption was significantly associated with lower prevalence of metabolic syndrome in Japanese male civil servants.

Objective-Although T-cell-mediated chronic inflammation contributes to atherosclerosis development, the role of a negative regulatory molecule cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) in atherosclerosis is poorly understood. We investigated the effects of CTLA-4 overexpression on atherosclerosis in apolipoprotein E-deficient (Apoe −/− ) mice. Approach and Results-We generated CTLA-4 transgenic (CTLA-4-Tg)/Apoe −/− mice that display constitutive cell surface and intracellular expression of CTLA-4 in T cells and assessed atherosclerosis at age 16 weeks. CTLA-4 overexpression significantly reduced atherosclerotic lesion formation and intraplaque accumulation of macrophage and CD4 + T cells in the aortic root compared with controls. CTLA-4-Tg/Apoe −/− mice showed decreased numbers of effector CD4 + T cells and decreased expression of costimulatory molecules CD80 and CD86, ligands for CTLA-4, and a costimulatory molecule CD28, on CD11c + dendritic cells compared with controls. Consistent with in vivo findings, in vitro experiments revealed that CD4 + T cells from CTLA-4-Tg/Apoe −/− mice showed decreased proliferative capacity and proinflammatory cytokine production, downregulated CD80 expression on CD11c + dendritic cells, and suppressed the proliferation of other T cells by limiting the costimulatory pathway. Moreover, CD11c+ dendritic cells from CTLA-4-Tg/Apoe −/− mice showed reduced proliferative activity of T cells in vitro, suggesting the suppression of dendritic cell maturation in vivo. Correspondence to Naoto Sasaki, MD, PhD. Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. E-mail: sasakin@med.kobe-u.ac.jp 9 As a homolog of CD28, CTLA-4 binds to CD80/ CD86 and suppresses T-cell activation. CTLA-4-deficient mice die prematurely from multiorgan inflammation, indicating CTLA-4 as a potent negative regulator of T-cell immune responses. Overexpression of Cytotoxic T-Lymphocyte-Associated Antigen-4 Prevents Atherosclerosis in Mice10 Polymorphism of the CTLA-4 gene is reported to be associated with susceptibility to a variety of autoimmune diseases in humans.11 Moreover, germline heterozygous mutations in CTLA4 in humans have been shown to result in dysregulation of CD4 + Foxp3 + Tregs and hyperactivation of Teffs and B cells and cause complex immune dysregulation syndrome 12 although heterozygous Ctla4 deficiency in mice shows no autoimmune phenotype.10 CTLA-4 is important for Treg-mediated suppression of autoimmune diseases 13 and possibly atheroprotection although there is no direct evidence on its role in Treg-mediated atheroprotection. CTLA-4-Ig, a soluble fusion protein consisting of the extracellular CD80/CD86 binding portion of CTLA-4, has been shown to be beneficial for the treatment of autoimmune disease and prevention of organ rejection.14 CTLA-4-Ig might be beneficial for the prevention of atherosclerotic lesion formation in atherosclerotic mice under specific conditions, such...

Invariant natural killer T cells (iNKT cells) are unique lymphocytes with characteristic features, such as expression of an invariant T cell antigen receptor (TCR) α chain, recognition of glycolipid antigens presented by CD1d molecules, and ability to rapidly produce large amounts of cytokines, including interferon-γ (IFNγ) and interleukin 4 (IL-4) upon TCR stimulation. Many studies have demonstrated that iNKT cells participate in immune response against diverse microbes, including bacteria, fungi, protozoan parasites and viruses. Generally, these cells play protective roles in host defense against infections. However, in some contexts they play pathogenic roles, by inducing or augmenting inflammation. Recent reports show that iNKT cells recognize glycolipid antigens from pathogenic bacteria including Streptococcus pneumoniae, and they contribute to host defense against infection. iNKT cell responses to these microbial glycolipid antigens are highly conserved between rodents and humans, suggesting that iNKT cells are evolutionally conserved because their invariant TCR is useful in detecting certain pathogens. Furthermore, glycolipid-mediated iNKT cell activation during immunization has adjuvant activity, enhancing humoral and cell-mediated responses. Therefore, iNKT cell activation is an attractive target for developing new vaccines for infectious diseases.

No abstract

No abstract