Conjugated linoleic acid modifies transcriptional cytokine profile and induces early specific secretory IgA response in Giardia lamblia infected mice.

Objectives: Adaptive immunity is crucial in controlling Giardia lamblia infection in the intestinal mucosa, and some dietary lipids may improve mucosal immune function. The aim of this study was to evaluate conjugated linoleic acid (CLA) on the Th17/Treg response and secretory IgA production in a model of giardiasis infection. Materials and Methods: C3H/HeN male mice were infected with 5×106 G. lamblia trophozoites (GS/M-83-H7, ATCC collection). Mice were assigned randomly to experimental and control groups. CLA was administered to the experimental group and phosphate-buffered saline (PBS) was given to the control group. Parasite load kinetics was determined. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate IgA and cytokines. Nuclear transcription factors and cytokines were measured by RT-qPCR, and histology of small bowel cells was evaluated. Results: CLA administration reduced the parasite load (P<0.05) and increased early Giardia-specific secretory IgA production. CLA also increased the expression of interleukin-10, transforming growth factor (TGF)-ß, and inducible nitric oxide synthase (iNOS) (P<0.05), while infection elevated the expression of Foxp3, with a peak at 40 days post-infection (P<0.05). There were no pathological changes in the colonic mucosa due to infection or treatment. Thus, CLA stimulated mucosal immunity and enhanced the humoral response against G. lamblia, not only for early infection control but also to promote regulatory cytokine production at 40 dpi, restoring the intestinal balance after parasite elimination. Conclusion: Our findings reveal novel anti-parasitic effects through the immune-modulatory activity of CLA against the intestinal parasite G. lamblia.

Central obesity and body fat, but not body mass index, are associated with the Pro12Ala polymorphism in the peroxisome proliferator-activated receptor γ gene in a population with a high consumption of saturated and trans-fatty acids.

The relationship of the Pro12Ala polymorphism in the peroxisome proliferator-activated receptor γ (PPARγ) gene with obesity and its modulation by dietary fat has been proposed, but the few studies addressing this issue have yielded controversial results. In a Mexican population characterized by high-fat consumption, we hypothesized that the Pro12Ala PPARγ genotype is related to obesity and this relationship is modulated by intake of saturated fatty acids (SFAs) and trans-fatty acids (TFAs). We recruited 69 adults for this cross-sectional study. The Pro12Ala PPARγ polymorphism was determined from blood genomic DNA by using real-time polymerase chain reaction. Univariate and multivariate logistic regression analyses were performed. Pro12Ala showed a positive association with central obesity (adjusted odds ratio, 7.38; 95% confidence interval, 1.19-45.77; P = .032) and percentage of body fat (%BF; adjusted odds ratio, 1.08; 95% confidence interval, 1.00-1.17; P = .048), suggesting that Pro12Ala carriers are more likely to have central obesity and a higher %BF than Pro12Pro carriers. A modifying effect was observed for the SFAs strata: we found a significant association between the Pro12Ala polymorphism and %BF in the high-SFA-intake stratum (P < .04), but not in the low-intake stratum (P > .7). No modifying effect was observed for the TFAs strata. In addition, the impact of total energy intake on obesity in Pro12Ala carriers seemed to be stronger than that in the wild-type genotype carriers. As hypothesized, our data demonstrated a relationship between the Pro12Ala PPARγ polymorphism and the presence of obesity, which is modulated by SFA intake but not TFA intake.

Production of interferon α and ß, pro-inflammatory cytokines and the expression of suppressor of cytokine signaling (SOCS) in obese subjects infected with influenza A/H1N1.

BACKGROUND & AIMS: Obesity was recognized as an independent risk factor for morbidity and mortality during last influenza A/H1N1 pandemic. Mechanisms involved in the high mortality risk from obesity during influenza A virus include reduced type I interferon production and delayed pro-inflammatory response, which lead to a higher rate of morbidity and mortality in murine models. In this study, we evaluated the production of type I interferons, pro-inflammatory and anti-inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) from obese and lean subjects with and without confirmed infection of influenza A/H1N1. The expression levels of the suppressor of cytokine signaling-1 (SOCS1), SOCS3 and nuclear factor-kB were also evaluated. METHODS: Cytokines were measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and/or by ELISA in PBMCs stimulated with toll like receptor-3 (TLR-3) and TLR-7 ligands. The mRNA expression of SOCS1 and SOCS3 were evaluated by qRT-PCR. RESULTS: The obese volunteers infected with influenza A/H1N1 showed a diminished ability to produce type I interferon in response to TLR-3 ligand. Interestingly, the pro-inflammatory response was also affected in TLR-3 stimulated PBMCs. Obese influenza-free volunteers showed an increased basal expression of SOCS3, but not SOCS1. During influenza infection, SOCS1 and SOCS3 expression was higher in the lean infected volunteers in contrast to those who were obese infected. CONCLUSIONS: These data suggest that obesity is related to TLR-3 impairment and explain, at least in part, the inadequate immune response of obese individuals during infection with influenza A/H1N1 virus.

Decreased interferon-α and interferon-ß production in obesity and expression of suppressor of cytokine signaling.

OBJECTIVE: We analyzed the interferon-α (IFN-α), IFN-ß, and proinflammatory responses induced by Toll-like receptor (TLR) ligands in peripheral blood mononuclear cells (PBMCs) from obese subjects and their association with suppressor of cytokine signaling-1 (SOCS1) and SOCS3 expression. METHODS: The IFN responses were measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay in PBMCs stimulated with TLR-3 and TLR-7 ligands from 30 non-obese (body mass index ≤ 25 kg/m(2)) and 30 obese (body mass index ≥ 30 kg/m(2)) volunteers. The mRNA expression of nuclear factor-κB, SOCS1, and SOCS3 also was evaluated by qRT-PCR. Proinflammatory cytokine responses were measured by enzyme-linked immunosorbent assay. RESULTS: Obese subjects showed a decreased ability to produce IFN-α and IFN-ß in response to TLR ligands; this response was associated with increased basal levels of SOCS3 but not SOCS1. However, after stimulation, the expression of SOCS3 and SOCS1 mRNA was significantly lower in PBMCs from obese compared with non-obese subjects. The PBMCs from obese subjects also showed higher basal levels of interleukin-6 and a decreased response of proinflammatory cytokines interleukin-6 and interleukin-1ß after stimulation with the TLR-3 ligand compared with PBMCs from non-obese participants. CONCLUSION: These data suggest that obesity is related to impaired IFN-α and IFN-ß responses and increased SOCS3 basal mRNA expression and that a signaling pathway by TLR-3 may be involved. These results could explain, at least in part, the inadequate response of obese people against viral infections, such as influenza.

Estimación de la masa grasa por DXA y el modelo de cuatro compartimentos en púberes mexicanos de 9 a 14 años / Estimation of body fat by DXA and the four compartment model in Mexican youth

Se evaluó la precisión y exactitud en la estimación de la grasa corporal (%) por absorciometría dual de rayos X (DXA Lunar-DPX-MD) comparado con el modelo de cuatro compartimentos (4C) en 32 púberes (F=16) de 9 a 14 años. El sesgo entre la DXA y el modelo de 4C fue de -3.5% de grasa (r=0.25; p=0.171) con un intervalo de confianza de -1.9 a -5.1 (p=0.050). Los límites de concordancia al 95% fueron de +5% a -12% de grasa. El coeficiente de correlación de concordancia fue de pc=0.85. La prueba de exactitud por análisis de regresión mostró que el intercepto y la pendiente de las estimaciones de grasa corporal por DXA fueron diferentes al modelo de 4C (p>0.05). La precisión evaluada con el valor de R2 mostró que la DXA explicó el 83% de la varianza de la grasa corporal por el modelo de 4C con un error de 4.1%. El error total como medida de exactitud fue de 5.6%. La exactitud grupal evaluada por análisis de varianza no mostró interacción entre el método (DXA-4C) y el análisis por separado del sexo, el estado puberal y la presencia de sobrepeso. No obstante, hubo efecto del método (p=0.043) en presencia de sobrepeso (p<0.001). En conclusión, los resultados muestran que el uso de la DXA comparado con el modelo de 4C no es equivalente en púberes mexicanos. Sin embargo, estos datos no limitan el uso de la DXA en estudios de composición corporal y su relación con anormalidades metabólicas.

The objective of this study was to validate the estimation of body fat (%BF) by DXA (Dual-Energy X-Ray AbsorciomDPX-MD) against the four compartment model (4C) of body composition in 32 Mexican pubertal girls and boys (aged 9 - 14y; F=16). The mean of the difference between DXA and 4C model was -3.5 %BF (p=0.171). The limits of agreement (95% ± 2 SD) were +5% to -12%BF. The precision of estimated limits of y the confidence intervals were -1.9% to -5.1%BF (P=0.050). The concordance correlation coefficient was pc= 0.85. The test of accuracy for coincidence of slop intercepts between DXA and the 4C model showed no coincidence (p< 0.05). The precision by R2 explained 83% of the variance (SEE, 4.1 %). The individual accuracy assess by the total error was 5.6%. The group mean accuracy by two way analysis of variance of body fat did not show interaction between method (DXA-4C model) and separate analysis of gender and overweight. However, there was an effect of method (p=0.043) in the presence of overweight (p<0.001). In conclusion, the estimation of percent of body fat by DXA was not precise and accurate in a group of Mexican children. However, results do not limit the utility of DXA for the measurements of body composition and its relation with health outcomes, especially in follow up studies.

Lifestyle intervention in primary care settings improves obesity parameters among Mexican youth.

Intervention studies in youth with obesity that can be translated into primary care are limited. We compared a lifestyle intervention to a brief intervention applied by primary care physicians (control group) for treating pediatric obesity in the primary care setting. Seventy-six youth with obesity (body mass index [BMI] >95th percentile or >90th percentile plus waist circumference >90th percentile, aged 9 to 17 years) participated in a 12-month, randomized, controlled trial, conducted at a primary care unit in Northern México from June 2006 through October 2007. Participants randomized to lifestyle intervention attended a family-centered program consisting of 12 sessions of behavioral curriculum, dietary advice from a registered dietitian (weekly for the first 3 months and monthly thereafter), and monthly consultations with a primary care physician. Control group participants attended monthly consultations with a primary care physician who received a brief training on obesity. Forty-three (57%) participants completed the 12 months of study. After 12 months, mean changes (95% confidence interval) in body weight for the lifestyle group and the control group were -0.8 kg (-3.2, 1.5) vs +5.6 kg (3, 8.2; P<0.001) and mean changes in BMI were -1.8 (-2.6, -0.9) vs +0.4 (-0.5, 1.3; P<0.001), respectively. Intention-to-treat analysis at 12 months confirmed significant differences in primary outcomes (weight -3.5 kg, P=0.02; BMI -1.2, P=0.03) in favor of the lifestyle group. This study provides preliminary evidence that primary care physicians supported by a registered dietitian and a behavioral curriculum can be a successful strategy for treating pediatric obesity in the primary care setting.

[Estimation of body fat by DXA and the four compartment model in Mexican youth]. / Estimación de la masa grasa por DXA y el modelo de cuatro compartimentos en púiberes mexicanos de 9 a 14 años.

The objective of this study was to validate the estimation of body fat (%BF) by DXA (Dual-Energy X-Ray AbsorciomDPX-MD) against the four compartment model (4C) of body composition in 32 Mexican pubertal girls and boys (aged 9-14 y; F=16). The mean of the difference between DXA and 4C model was -3.5 %BF (p=0.171). The limits of agreement (95% = 2 SD) were +5% to -12%BF. The precision of estimated limits of y the confidence intervals were -1.9% to -5.1%BF (P = 0.050). The concordance correlation coefficient was p = 0.85. The test of accuracy for coincidence of slop intercepts between DXA and the 4C model showed no coincidence (p < 0.05). The precision by R2 explained 83% of the variance (SEE, 4.1%). The individual accuracy assess by the total error was 5.6%. The group mean accuracy by two way analysis of variance of body fat did not show interaction between method (DXA-4C model) and separate analysis of gender and overweight. However, there was an effect of method (p = 0.043) in the presence of overweight (p < 0.001). In conclusion, the estimation of percent of body fat by DXA was not precise and accurate in a group of Mexican children. However, results do not limit the utility of DXA for the measurements of body composition and its relation with health outcomes, especially in follow up studies.

In vitro effect of vitamin E on lectin-stimulated porcine peripheral blood mononuclear cells.

In order to analyze the effect of vitamin E on Th1 and Th2 cytokine production, porcine peripheral blood mononuclear cells (PBMC) were isolated from healthy pigs (n=8) and cultured with either 0, 10, 50, or 100muM of vitamin E (alpha-tocopherol). PBMC were stimulated with PHA for either, 24h to determine: (a) the concentration of tocopherol incorporated into the cell membrane, (b) cytokine production and (c) Th1 and Th2 regulators gene expression; or 72h to determine the proliferation of PBMC. Vitamin E was incorporated into the PBMC in a dose dependent manner, giving as a result a high proliferation of cells irrespective of the dose of vitamin E used. Regarding cytokine production, vitamin E consistently decreases the mRNA expression and the percentage of cells producing IL-10. Vitamin E did not influence the production of IFN-gamma but the lowest level of vitamin E (10muM) was sufficient to maximally increase the proportion of cells producing IL-2, to diminish IL-4, and discreetly increase the mRNA expression of TBX21 vs. GATA3. In conclusion, our results revealed that vitamin E is able to suppress IL-10 production and to influence the production of IL-2, IL-4, and maybe TBX21. Vitamin E clearly has immunomodulatory effects, though further work in vivo to determine the physiological nature of these effects is warranted.

Helicobacter pylori is not associated with anaemia in Latin America: results from Argentina, Brazil, Bolivia, Cuba, Mexico and Venezuela.

OBJECTIVE: To investigate the association between Helicobacter pylori infection and anaemia. DESIGN: Six cross-sectional studies. H. pylori infection was assessed by the [13C]urea breath test using MS or IR analysis. Hb was measured for all countries. Ferritin and transferrin receptors were measured for Argentina, Bolivia, Mexico, and Venezuela. SETTING: Health services in Argentina, Brazil and Mexico or public schools in Bolivia, Cuba and Venezuela. SUBJECTS: In Argentina, 307 children aged 4-17 years referred to a gastroenterology unit; in Bolivia, 424 randomly selected schoolchildren aged 5-8 years; in Brazil, 1007 adults (157 men, 850 women) aged 18-45 years attending thirty-one primary health-care units; in Cuba, 996 randomly selected schoolchildren aged 6-14 years; in Mexico, seventy-one pregnant women in their first trimester attending public health clinics; in Venezuela, 418 children aged 4-13 years attending public schools. RESULTS: The lowest prevalence of H. pylori found was among children in Argentina (25.1%) and the highest in Bolivia (74.0%). In Bolivia, Cuba and Venezuela children showed similar prevalence of H. pylori infection as in Brazilian and Mexican adults (range 47.5% to 81.8%). Overall anaemia prevalence was 11.3% in Argentina, 15.4% in Bolivia, 20.6% in Brazil, 10.5% in Cuba and 8.9% in Venezuela. Adjusted analyses allowing for confounding variables showed no association between H. pylori colonization and anaemia in any study. Hb, ferritin and transferrin receptor levels were also not associated with H. pylori infection in any country. CONCLUSIONS: The present study showed no evidence to support the hypothesis that H. pylori contributes to anaemia in children, adolescents, adults or pregnant women in six Latin American countries.

Four-compartment model and validation of deuterium dilution technique to estimate fat-free mass in Mexican youth.

OBJECTIVE: To validate the measurement of fat-free mass (FFM) with the deuterium oxide (D(2)O) dilution technique (2C) against the four-compartment (4C) model in Mexican children. METHODS: This was designed as a cross-sectional, non-probabilistic study. Sixty subjects (30 male and 30 female) 6-14 y of age were recruited and completed the study during 5 mo. Total body water was measured using the D(2)O dilution technique and FFM was calculated using Fomon's (6-10 y) and Lohman's (11-14 y) hydration constants. Body composition using the 4C model was calculated with Lohman's equation. RESULTS: Group mean accuracy showed no differences in FFM determined by D(2)O dilution and the 4C model (1.24 kg, P > 0.4), by gender (2.1 kg, P > 0.2), or by method-by-gender interaction (P > 0.7). FFMs were 26.9 and 25.7 kg by the 4C and 2C models, respectively. The test for coincidence of slopes and intercepts between the 2C and 4C models and the line of identity were not different (P > 0.05). Precision by R(2) explained 98% of the variance (standard error of the estimate 1.2 kg). Bias for the difference in FFM was not significant (-1.27, 95% confidence interval -1.5 to -0.9) and no association between the mean of the differences and the magnitude of the measurements was found (P > 0.05). Mean bias was -1.27 kg for FFM (P > 0.05), and limits of agreement were -3.1 to 0.8 kg. CONCLUSION: The D(2)O dilution technique used with these hydration constants was accurate, precise, and free of bias in Mexican children and adolescents compared with the 4C model.

Effects of asymptomatic Giardia intestinalis infection on carbohydrate absorption in well-nourished Mexican children.

The aim of this study was to evaluate carbohydrate absorption in well-nourished children with asymptomatic giardiasis. Two groups were selected based on results of stool examination of 211 children attending pre-school centers in Hermosillo, Sonora, Mexico: a control group of six non-infected children, and an infected group of seven children harboring Giardia intestinalis, without gastrointestinal symptoms of disease. Carbohydrate absorption was determined in the control group, before and after drug therapy in the infected group by the hydrogen breath test. Hydrogen production after lactose ingestion was higher in children with giardiasis compared with control group and after anti-parasite treatment; however, hydrogen production was not high enough to classify children as lactose malabsorbers by the cut-off criteria. Similar results were obtained for xylose absorption. None of the children had hydrogen increments high enough to be considered xylose malabsorbers. In conclusion, children asymptomatically infected with G. intestinalis showed significantly higher hydrogen production. However, the biological relevance is questionable since they did not exceed cut-off criteria to classify them as carbohydrate malabsorbers.