Effect of plant sterols and exercise training on cholesterol absorption and synthesis in previously sedentary hypercholesterolemic subjects

Plant sterols combined with exercise beneficially alter lipid profiles in hypercholesterolemic adults. Although the mechanism by which plant sterols favorably modulate lipid levels is well established, no trial to date has examined the effect of exercise, alone or combined with plant sterols, on cholesterol kinetics. Thus, the current objective was to examine the effects of exercise, plant sterols, and the combination of exercise and plant sterols on cholesterol absorption and synthesis. In an 8-week, parallel-arm trial, 84 subjects were randomized to 1 of 4 interventions: plant sterols combined with exercise, plant sterols, exercise, or control. Diets were not controlled. Total cholesterol and triglyceride levels decreased (P<0.01) by 7.7% and 11.8%, respectively, whereas high-density lipoprotein (HDL) cholesterol levels increased (P<0.01) by 7.5% in the combination group. Mean posttreatment low-density lipoprotein (LDL) cholesterol levels decreased (P<0.01) by 0.30 mmol/L in the combination group. Cholesterol absorption was 16% lower (P<0.01) in the combination group and 18% lower (P<0.01) in the plant sterol group, when compared with control. Exercise had no effect on cholesterol absorption. Nonsignificant increases in cholesterol synthesis rates of 63% (0.084+/-0.014 pools/day), 59% (0.075+/-0.013 pools/day), and 57% (0.072+/-0.011 pools/day) were observed in the combination, exercise, and plant sterol groups, respectively, relative to the control group (0.031+/-0.019 pools/day). LDL cholesterol levels correlated with cholesterol absorption, as represented by the area under the deuterium enrichment curve (r=0.23, P=0.05), and with percent absorption relative to control (r=0.25, P=0.03). These findings suggest that exercise does not modulate lipid levels by altering to cholesterol absorption or synthesis, whereas plant sterols favorably alter levels of LDL cholesterol by suppressing intestinal absorption.     

The impact of langerin (CD207)+ dendritic cells and FOXP3+ Treg cells in the small bowel mucosa of children with celiac disease and atopic dermatitis in comparison to children with functional gastrointestinal disorders

In the present study we aimed to evaluate the impact of langerin (CD207)+ dendritic cells (DCs) and FOXP3+ Treg cells in the intestinal mucosa of children with celiac disease (CD) and atopic dermatitis (AD) in comparison to children with functional gastrointestinal disorders (FGD). Seventy‐five children (37 male, mean age 8.4 ± 4.8 years), who randomly underwent small bowel biopsy, were studied. The CD was diagnosed in 14 children, including five persons with concomitant AD (all positive for anti‐tissue transglutaminase IgA antibodies and with small bowel atrophy). Normal small bowel mucosa was found in eight patients with AD and in 53 patients with FGD. The sera of all patients were tested for total and specific IgE antibodies to food allergen panels. Staining for CD11c+, langerin (CD207+) DCs, CD4+, and FOXP3+ Treg cells was performed on paraffin‐embedded sections of bioptates using immunohistochemistry. The density of CD11c+ DCs, CD4+, and FOXP3+ Treg cells was higher in the CD patients compared to the AD and FGD patients (p = 0.02; p = 0.001). In AD, significantly higher density of CD11c+ DCs was detected in patients positive for specific IgE to food allergen panels (p = 0.02). The FGD patients with elevated total IgE had increased density of langerin (CD207)+ DCs compared to the patients with normal total IgE levels (p = 0.01). The increased density of FOXP3+ Treg cells, CD4+, cells and CD11c+ DCs was associated with CD but not with AD. The elevated level of total IgE or specific IgE to food allergens was associated with more pronounced expression of DCs, indicating a possible link between the presence of these cells in small bowel mucosa with elevated level of serum IgE.     

Metabolic and phenotypic characteristics of human skeletal muscle fibers as predictors of glycogen utilization during electrical stimulation

Characteristics of skeletal muscle such as fiber type composition and activities of key metabolic enzymes have been purported to affect glycogen utilization. However, the relative importance individual factors may have in predicting glycogen utilization of individual muscle fibers has not been addressed. Thus, we sought to determine the relative importance that metabolic characteristics and phenotypic expression of individual fibers have in predicting fiber specific glycogen utilization during neuromuscular electrical stimulation (NMES) exercise. Biopsies were taken from the m, vastus lateralis (VL) of eight recreationally active males before and immediately after 30 min of non-fatiguing NMES and analyzed for type (I, IIa and IIx), succinate dehydrogenase activity (SDH), glycerol-phosphate dehydrogenase activity (GPDH), quantitative-actomyosin adenosine triphosphatase activity (qATPase), and glycogen content. Our results demonstrate that a ratio of enzyme activities representing pathways for energy supply and energy demand (SDH: qATPase) accounted for more of the variance in glycogen utilization (y=0.2091 e^−0.0329x , R ²=0.622, P≤ 0.0001) than SDH (R ²=0.321) or qATPase (R ²=0.365) alone. Fiber phenotype was also a significant predictor of glycogen utilization, but to a lesser extent than the other variables studied (R ²=0.201). A ratio of the activities of enzymes representing pathways of energy supply and energy demand, represented by SDH:qATPase, is a better predictor of glycogen utilization than either of its components independently while fiber phenotype, although a statistically significant predictor of glycogen utilization, may not be the most appropriate determinate of the functional characteristics of an individual fiber.     

Bacterial characteristics in relation to clinical source of Escherichia coli isolates from women with acute cystitis or pyelonephritis and uninfected women

Characteristics differentiating Escherichia coli strains that cause cystitis or pyelonephritis from fecal E. coli remain incompletely defined, particularly among adult women in the United States. Accordingly, phylogenetic group, O antigens, and virulence factors (VFs) were analyzed among 329 E. coli isolates from the mid-to-late 1990s from women in the United States with acute pyelonephritis (n = 170), cystitis (n = 83), or no infection (fecal; n = 76). Compared with fecal and cystitis isolates, pyelonephritis isolates exhibited a greater prevalence of phylogenetic group B2, most virulence-associated O antigens, and most VFs and had higher VF scores. In contrast, cystitis and fecal isolates differed minimally. By stepwise multivariable logistic regression, significant (P < or = 0.015) predictors of cystitis and/or pyelonephritis (versus fecal) included afa/dra (Dr-binding adhesins), ibeA (invasion of brain endothelium), iha (putative adhesin-siderophore), malX (pathogenicity island marker), the O75 antigen, papEF (P fimbriae), papG allele II (P adhesin variant), group B2, and sfa/foc (S and F1C fimbriae). However, virulence profiles overlapped considerably among source groups and varied greatly within each group. E. coli "clonal group A" (CGA) and the O2:K5/K7:H1 and O75:K+ clonal groups were significantly associated with cystitis and/or pyelonephritis. These findings identify potential vaccine targets, suggest that urovirulence is multiply determined, and confirm the urovirulence of specific E. coli clonal groups, including recently recognized CGA.     

Rapid and specific detection of Escherichia coli clonal group A by gene-specific PCR

PCR primers specific for the recently described antimicrobial resistance-associated Escherichia coli clonal group A (CGA), a widespread cause of drug-resistant urinary tract infections in the United States, were devised on the basis of a novel single-nucleotide polymorphism identified within the housekeeping gene fumC, i.e., C288T. In comparison with two reference PCR-based fingerprinting methods, ERIC2 PCR and random amplified polymorphic DNA (RAPD) analysis, a PCR assay incorporating the new primers provided 100% sensitivity and 100% specificity for the detection of CGA among 138 diverse clinical and reference E. coli isolates. E. coli reference (ECOR) strain 47 was shown to be a member or a close relative of CGA (by ERIC2 PCR and RAPD analysis, respectively) and yielded a positive assay result. The new CGA-specific PCR assay, which exhibited interlaboratory reproducibility and stability under various experimental conditions, should allow the rapid and specific detection of CGA by any laboratory equipped for diagnostic PCR.     

Double- and monofunctional CD4⁺ and CD8⁺ T-cell responses to Mycobacterium tuberculosis DosR antigens and peptides in long-term latently infected individuals

More than 2 billion individuals are latently infected with Mycobacterium tuberculosis (Mtb). Knowledge of the key Mtb antigens and responding T-cell subsets mediating protection against Mtb is critical for developing improved tuberculosis (TB) vaccines. We previously reported that Mtb DosR-regulon-encoded antigens are recognized well by human T cells in association with control of Mtb infection. The characteristics of the responding T-cell subsets, however, remained unidentified. We have therefore studied the cytokine production and memory phenotypes of Mtb DosR-regulon-encoded antigen-specific T cells from individuals who had been infected with Mtb decades ago, yet never developed TB (long-term latent Mtb-infected individuals). Using multi-parameter flow cytometry and intracellular cytokine staining for IFN-γ, TNF-α and IL-2, we found double and single cytokine-producing CD4(+) as well as CD8(+) T cells to be the most prominent subsets, particularly IFN-γ(+) TNF-α(+) CD8(+) T cells. The majority of these T cells comprised effector memory and effector T cells. Furthermore, CFSE labeling revealed strong CD4(+) and CD8(+) T-cell proliferative responses induced by several "immunodominant" Mtb DosR antigens and their specific peptide epitopes. These findings demonstrate the prominent presence of double- and monofunctional CD4(+) and CD8(+) T-cell responses in naturally protected individuals and support the possibility of designing Mtb DosR antigen-based TB vaccines.