Effects of PM10 Airborne Particles from Different Regions of a Megacity on In Vitro Secretion of Cytokines by a Monocyte Line during Different Seasons.

Several epidemiological studies have demonstrated that particulate matter (PM) in air pollution can be involved in the genesis or aggravation of different cardiovascular, respiratory, perinatal, and cancer diseases. This study assessed the in vitro effects of PM10 on the secretion of cytokines by a human monocytic cell line (THP-1). We compared the chemotactic, pro-inflammatory, and anti-inflammatory cytokines induced by PM10 collected for two years during three different seasons in five different Mexico City locations. MIP-1α, IP-10, MCP-1, TNF-α, and VEGF were the main secretion products after stimulation with 80 µg/mL of PM10 for 24 h. The THP-1 cells showed a differential response to PM10 obtained in the different sites of Mexico City. The PM10 from the north and the central city areas induced a higher pro-inflammatory cytokine response than those from the south. Seasonal pro-inflammatory cytokine secretion always exceeded anti-inflammatory secretion. The rainy-season-derived particles caused the lowest pro-inflammatory effects. We concluded that toxicological assessment of airborne particles provides evidence supporting their potential role in the chronic exacerbation of local or systemic inflammatory responses that may worsen the evolution of some chronic diseases.

Cervicovaginal Cytokines to Predict the Onset of Normal and Preterm Labor: a Pseudo-longitudinal Study.

Inflammatory processes associated with human parturition are still not completely understood, not only because the gap between inflammation and the onset of labor has been difficult to study but also because of the limited knowledge about the role of cervicovaginal fluid (CVF) cytokines during the sequence of labor. We aimed to determine whether CVF cytokines could predict the onset of normal and preterm labor. Chemokines and proinflammatory and anti-inflammatory cytokines in CVF were measured in a pseudo-longitudinal manner in healthy women between 12 and 41 weeks gestation with intact fetal membranes before and during the first stage of labor. Women were grouped into five stages, from the absence of uterine activity and cervical changes to regular uterine contractions with cervix dilation > 3 cm (active phase of labor). Of 144 women with spontaneous labor, 96 gave birth at term, 48 gave birth preterm, and both groups displayed similar cytokine concentrations. We found positive correlations between proinflammatory cytokines and the initial sequence of labor, using individual cytokines and score-based data by principal component analysis (IFN-γ, TNF-α, IL-1ß, IL-6) as dependent variables. The risk of labor onset increased as the concentrations of IL-6 increased (hazard ratio = 202.09, 95% confidence interval = 24.57-1662.49, P < 0.001). The IL-6 concentration predicted the onset of labor within 12 days of sampling (area under the time-dependent ROC curve = 0.785, 95% confidence interval = 0.693-0.877). Here, we showed that regardless of gestational age, the onset of labor could be predicted by the IL-6 concentration in the CVF, since the initial sequence of spontaneous labor displayed an inflammatory response expressed by the increase in proinflammatory cytokines.

Sex-differential RXRα gene methylation effects on mRNA and protein expression in umbilical cord of the offspring rat exposed to maternal obesity.

Maternal obesity (MO) induces negative consequences in the offspring development. Adiposity phenotype is associated with maternal diet at early pregnancy and DNA methylation marks in the RXRα promotor at birth. Glucocorticoids play an important role in the regulation of metabolism through the activation of nuclear hormone receptors such as the RXRα protein. The aim of the study was to analyze steroid hormone changes at the end of pregnancy in the obese mother and RXRα gene methylation in the umbilical cord. For this purpose, in a well-established MO model, female Wistar rats were fed either standard chow (controls: C) or high-fat obesogenic diet (MO) before and during pregnancy to evaluate at 19 days of gestation (19 dG): 1) maternal concentration of circulating steroid hormones in MO and C groups, 2) maternal and fetal weights, 3) analysis of correlation between hormones concentration and maternal and fetal weights, 4) DNA methylation status of a single locus of RXRα gene near the early growth response (EGR-1) protein DNA binding site, and 5) RXRα mRNA and protein expressions in umbilical cords. Our results demonstrate that at 19 dG, MO body weight before and during pregnancy was higher than C; MO progesterone and corticosterone serum concentrations were higher and estradiol lower than C. There were not differences in fetal weight between male and female per group, therefore averaged data was used; MO fetal weight was lower than C. Positive correlations were found between progesterone and corticosterone with maternal weight, and estradiol with fetal weight, while negative correlation was observed between corticosterone and fetal weight. Additionally, male umbilical cords from MO were hypermethylated in RXRα gene compared to male C group, without differences in the female groups; mRNA and protein expression of RXRα were decreased in F1 male but not in female MO compared to C. In conclusion, MO results in dysregulation of circulating steroid hormones of the obese mothers and low fetal weight in the F1, modifying DNA methylation of RXRα gene as well as RXRα mRNA and protein expression in the umbilical cord in a sex-dependent manner.

Sera from women with different metabolic and menopause states differentially regulate cell viability and Akt activation in a breast cancer in-vitro model.

Obesity is associated with an increased incidence and aggressiveness of breast cancer and is estimated to increment the development of this tumor by 50 to 86%. These associations are driven, in part, by changes in the serum molecules. Epidemiological studies have reported that Metformin reduces the incidence of obesity-associated cancer, probably by regulating the metabolic state. In this study, we evaluated in a breast cancer in-vitro model the activation of the IR-ß/Akt/p70S6K pathway by exposure to human sera with different metabolic and hormonal characteristics. Furthermore, we evaluated the effect of brief Metformin treatment on sera of obese postmenopausal women and its impact on Akt and NF-κB activation. We demonstrated that MCF-7 cells represent a robust cellular model to differentiate Akt pathway activation influenced by the stimulation with sera from obese women, resulting in increased cell viability rates compared to cells stimulated with sera from normal-weight women. In particular, stimulation with sera from postmenopausal obese women showed an increase in the phosphorylation of IR-ß and Akt proteins. These effects were reversed after exposure of MCF-7 cells to sera from postmenopausal obese women with insulin resistance with Metformin treatment. Whereas sera from women without insulin resistance affected NF-κB regulation. We further demonstrated that sera from post-Metformin obese women induced an increase in p38 phosphorylation, independent of insulin resistance. Our results suggest a possible mechanism in which obesity-mediated serum molecules could enhance the development of luminal A-breast cancer by increasing Akt activation. Further, we provided evidence that the phenomenon was reversed by Metformin treatment in a subgroup of women.

ELABELA plasma concentrations are increased in women with late-onset preeclampsia.

Objective: ELABELA is a newly discovered peptide hormone that appears to be implicated in the mechanisms leading to preeclampsia, independently of angiogenic factors. The aim of the current study was to investigate whether women with early- or late-onset preeclampsia have altered ELABELA plasma concentrations compared to gestational-age-matched normal pregnant women.Methods: This retrospective cross-sectional study focused on the maternal plasma samples collected from 232 women with a singleton pregnancy who were allocated into the following groups: (1) early-onset preeclampsia (<34 weeks of gestation, N = 56); (2) late-onset preeclampsia (≥34 weeks of gestation, N = 57); and (3) gestational-age-matched controls with a normal pregnancy [(<34 weeks of gestation, N = 59); (≥34 weeks of gestation, N = 60)]. ELABELA plasma concentrations were determined using a validated enzyme immunoassay.Results: (1) ELABELA plasma concentrations are higher in patients with late-onset preeclampsia compared with those from gestational-age-matched controls with a normal pregnancy [median: 7.99 ng/mL (IQR, 5.3-13.95 ng/mL) versus median: 4.17 ng/mL (IQR, 3-11.19 ng/mL), p =.001]; (2) ELABELA plasma concentrations in patients with early-onset preeclampsia do not differ from those of normal pregnant women [median: 6.09 ng/mL (IQR, 2.8-10.66 ng/mL) versus median: 4.02 ng/mL (IQR, 3.26-7.49), p = .32]; and (3) ELABELA plasma concentrations are higher in patients with late-onset preeclampsia compared to those with early-onset preeclampsia [median: 7.99 ng/mL (IQR, 5.3-13.95 ng/mL) versus median: 6.09 ng/mL (IQR, 2.8-10.66 ng/mL), p = .01].Conclusion: ELABELA plasma concentrations are higher in patients with late-onset preeclampsia than in those with a normal pregnancy. However, women with early-onset preeclampsia have similar ELABELA plasma concentrations to those with a normal pregnancy. These findings provide insight into the ELABELA axis during the human syndrome of preeclampsia. In addition, these data support the concept that different pathophysiologic mechanisms are implicated in early- and late-onset preeclampsia.

Photoacoustic imaging of the uterine cervix to assess collagen and water content changes in murine pregnancy.

The uterine cervix plays a central role in the maintenance of pregnancy and in the process of parturition. Cervical remodeling involves dramatic changes in extracellular matrix composition and, in particular, of collagen and water content during cervical ripening (a term that describes the anatomical, biochemical, and physiologic changes in preparation for labor). Untimely cervical ripening in early gestation predisposes to preterm labor and delivery, the leading cause of infant death worldwide. Inadequate ripening of the cervix is associated with failure of induction or prolonged labor. The current approach to evaluate the state of the cervix relies on digital examination and sonographic examination. Herein, we present a novel imaging method that combines ultrasound (US) and photoacoustic (PA) techniques to evaluate cervical remodeling by assessing the relative collagen and water content of this organ. The method was tested in vitro in extracted collagen phantoms and ex vivo in murine cervical tissues that were collected in mid-pregnancy and at term. We report, for the first time, that our imaging approach provides information about the molecular changes in the cervix at different gestational ages. There was a strong correlation between the results of PA imaging and the histological assessment of the uterine cervix over the course of gestation. These findings suggest that PA imaging is a powerful method to assess the biochemical composition of the cervix and open avenues to non-invasively investigate the composition of this organ, which is essential for reproductive success.

Effect of interscalene nerve block on the inflammatory response in shoulder surgery: a randomized trial.

BACKGROUND: Comparing techniques of general anesthesia and regional anesthesia in arthroscopic shoulder surgery, some studies have shown differences in the intensity of immediate postoperative pain and neuroendocrine response, but the inflammatory response when using balanced general anesthesia (BGA) vs. an ultrasound-guided (USG) single-dose interscalene block (SDIB) has not been compared. MATERIALS AND METHODS: In a single-center, prospective, randomized clinical trial, the inflammatory response of 2 groups of 10 patients scheduled to undergo arthroscopic shoulder surgery was evaluated through measurement of a panel of cytokines that act on cells of the adaptive immune response to promote or inhibit inflammation, chemokines involved in chemotaxis, the erythrocyte sedimentation rate (ESR), the high-sensitivity C-reactive protein (CRP) level, and the white blood cell (WBC) count in 3 blood samples (before anesthesia, immediately postoperatively, and 24 hours postoperatively) with 2 types of anesthesia (BGA vs. USG SDIB). Postoperative pain intensity (immediately, at 12 hours, and at 24 hours) was also assessed. RESULTS: The ESR and CRP level increased significantly at 24 hours after surgery; however, the increase in ESR (P < .0001) and CRP level (P < .0001) was lower in the USG SDIB group. Significant increases in the levels of soluble interleukin 2 receptor α (P = .022) and interleukin 12p40 (P = .016) occurred in the immediate postoperative period in the USG SDIB group. Immediate postoperative pain showed a significant increase (P < .001) in the BGA group. CONCLUSIONS: In arthroscopic shoulder surgery, the use of a USG SDIB compared with the use of BGA is possibly associated with improved pain control in the immediate postoperative period and lower immunosuppression, even at 24 hours after surgery.

Effect of soluble factors derived from ZR 75.30 breast cancer cells on endothelial activation.

In this study, we analyzed soluble factors secreted by two Estrogen Receptor Positive (ER-α) human breast cancer cell lines, ZR 75.30 (luminal B) and MCF7 (luminal A), and evaluated their effect on endothelial activation. The composition of tumoral soluble factors (TSFs) was analyzed by ELISA (Bio-Plex). TSFs from ZR 75.30 cells expressed higher levels of TNF, IFN-γ, IL-6, and IL-8 compared to TSFs from MCF-7 cells. TSFs from ZR 75.30 cells induced a pro-adhesive phenotype in human umbilical vein endothelial cells (HUVECs), as characterized by increased monocytic cell adhesion, adhesion molecule expression and NF-κB activation and decreased IκB-α expression. Conversely, TSFs from MCF-7 cells exerted none of these effects on HUVECs. We then added TNF, IFN-γ, IL-6 or IL-8 alone or in combination with TSFs from MCF-7 cells to HUVECs. Only the combinations that included TNF induced endothelial activation. A neutralizing antibody against IL-1ß (this cytokine was not measured in the ELISA) had a modest blocking effect on cellular adhesion or the expression of adhesion molecules induced by TSFs from ZR 75.30 cells in HUVECs. However neutralizing antibodies against TNF, IFN-γ, IL-6 or IL-8 had no effect. Our results suggest that although TNF is an inducer of endothelial cell activation, it is not the only molecule that is responsible for this effect in TSFs from ZR 75.30 cells.

Malformación arteriovenosa uterina congénita. Presentación de un caso con hemorragia uterina masiva / Congenital uterine arteriovenous malformation. A case of massive uterine hemorrhage

Resumen Antecedentes Las malformaciones arteriovenosas uterinas son raras y un diagnóstico diferencial poco considerado. Caso clínico Paciente de 27 años que acudió a urgencias debido a hemorragia uterina abundante y abrupta, con alteración del estado hemodinámico. Antecedentes personales: malformaciones en el sistema vascular. Con base en estudios de imagen se diagnosticó una malformación arteriovenosa uterina que, por sus antecedentes, se consideró congénita. Con el propósito de disminuir los riesgos de la histerectomía y conservar la fertilidad se indicó tratamiento conservador con embolización arterial transcatéter del sistema arteriovenoso uterino afectado, con gelfoam. Conclusiones La malformación arteriovenosa uterina es una posible causa de hemorragia uterina masiva; por tanto, debe considerarse en casos con antecedentes relevantes. Hay opciones de tratamiento que detienen la hemorragia y preservan la capacidad reproductiva. Para esto es preciso contar con un equipo multidisciplinario que identifique el sitio del defecto y aplique, de forma dirigida, la embolización arterial transcatéter de los vasos uterinos.

Abstract BACKGROUND Uterine arteriovenous malformations are a rare condition, and the differential diagnosis is often not considered when massive uterine hemorrhage occurs. Clinical case A case of massive uterine hemorrhage is presented in a 27- year-old woman with medical history of vascular malformations. Imaging studies diagnosed uterine arteriovenous malformation (AVM), which by her medical history was considered congenital. The patient was treated with Gelfoam uterine arterial transcatheter vascular embolization (TAE), with the purpose of reducing the risks of hysterectomy and preserving fertility. Conclusions The uterine arteriovenous malformation is a possible cause of massive uterine hemorrhage; therefore, it should be consid ered in cases with a relevant background. There are treatment options that stop the hemorrhage and preserve the reproductive capacity. For this, it is necessary to have a multidisciplinary team that identifies the site of the defect and applies, in a targeted manner, transcatheter arterial embolization of the uterine vessels.

Improvement of cardiometabolic markers after fish oil intervention in young Mexican adults and the role of PPARα L162V and PPARγ2 P12A.

Polyunsaturated fatty acids (PUFA) contained in fish oil (FO) are ligands for peroxisome proliferator-activated receptors (PPAR) that may induce changes in cardiometabolic markers. Variation in PPAR genes may influence the beneficial responses linked to FO supplementation in young adults. The study aimed to analyze the effect of FO supplementation on glucose metabolism, circulating lipids and inflammation according to PPARα L162V and PPARγ2 P12A genotypes in young Mexican adults. 191 young, non-smoking subjects between 18 and 40 years were included in a one-arm study. Participants were supplemented with 2.7 g/day of EPA+DHA, during six weeks. Dietary analysis, body composition measurements and indicators for glucose metabolism, circulating lipids, and markers for inflammation were analyzed before and after intervention. An overall decrease in triglycerides (TG) and an increase in HS-ω3 index were observed in all subjects [-4.1 mg/dL, (SD:±51.7), P=.02 and 2.6%, (SD:±1.2), P<.001 respectively]. Mean fasting insulin and glycated hemoglobin (HbA1c%) were significantly decreased in all subjects [-0.547mlU/L, (SD:±10.29), P=.034 and-0.07%, (SD:±0.3), P<.001 respectively], whereas there was no change in body composition, fasting glucose, adiponectin and inflammatory markers. Subjects carrying the minor alleles of PPARα L162V and PPARγ2 P12A had higher responses in reduction of TG and fasting insulin respectively. Interestingly, doses below 2.7 g/day (1.8 g/day) were sufficient to induce a significant reduction in fasting insulin and HbA1c% from baseline (P=.019 and P<.001). The observed responses in triglycerides and fasting insulin in the Mexican population give further evidence of the importance of FO supplementation in young people as an early step towards the prevention of cardiometabolic disease.

An intervention to promote physical activity in Mexican elementary school students: building public policy to prevent noncommunicable diseases.

Physical activity is an important component of strategies for health promotion and prevention of noncommunicable diseases. It is also associated with decreased risk for cardiovascular disease in overweight and obese adults and children. This article addresses the initial description of a physical activity intervention for children attending public elementary schools in Mexico. The objective was to develop a replicable model based on a strategic public, private, academic, and social partnership that would have a short-term impact on the metabolic health of children and be useful for building effective public policy. Forty-nine schools (20 000 students) participated, and 5 schools were selected for evaluation. The intervention included a 30-minute supervised middle-effort interchangeable routine, 5 days a week for a complete school year, adapted for different school conditions and students of different ages. Evaluation included anthropometric measurements and biochemical markers. Actual prevalence of combined overweight and obesity in these children was 31.9%. The intervention was successfully implemented in all schools. No change in body mass index, waist circumference, or other anthropometric indicators was found. However, changes in biochemical markers showed a significant decrease in blood glucose, total cholesterol, and cholesterol-low-density lipoproteins, reflecting a positive effect on cardiovascular health indicators.

TNFα and IL-6 Responses to Particulate Matter in Vitro: Variation According to PM Size, Season, and Polycyclic Aromatic Hydrocarbon and Soil Content.

BACKGROUND: Observed seasonal differences in particulate matter (PM) associations with human health may be due to their composition and to toxicity-related seasonal interactions. OBJECTIVES: We assessed seasonality in PM composition and in vitro PM pro-inflammatory potential using multiple PM samples. METHODS: We collected 90 weekly PM10 and PM2.5 samples during the rainy-warm and dry-cold seasons in five urban areas with different pollution sources. The elements, polycyclic aromatic hydrocarbons (PAHs), and endotoxins identified in the samples were subjected to principal component analysis (PCA). We tested the potential of the PM to induce tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6) secretion in cultured human monocytes (THP-1), and we modeled pro-inflammatory responses using the component scores. RESULTS: PM composition varied by size and by season. PCA identified two main components that varied by season. Combustion-related constituents (e.g., vanadium, benzo[a]pyrene, benzo[a]anthracene) mainly comprised component 1 (C1). Soil-related constituents (e.g., endotoxins, silicon, aluminum) mainly comprised component 2 (C2). PM from the rainy-warm season was high in C2. PM (particularly PM2.5) from the dry-cold season was rich in C1. Elevated levels of cytokine production were associated with PM10 and C2 (rainy-warm season), whereas reduced levels of cytokine production were associated with PM2.5 and C1 (dry-cold season). TNFα secretion was increased following exposure to PM with high (vs. low) C2 content, but TNFα secretion in response to PM was decreased following exposure to samples containing ≥ 0.1% of C1-related PAHs, regardless of C2 content. The results of the IL-6 assays suggested more complex interactions between PM components and particle size. CONCLUSIONS: Variations in PM soil and PAH content underlie seasonal and PM size-related patterns in TNFα secretion. These results suggest that the mixture of components in PM explains some seasonal differences in associations between health outcomes and PM in epidemiologic studies. CITATION: Manzano-León N, Serrano-Lomelin J, Sánchez BN, Quintana-Belmares R, Vega E, Vázquez-López I, Rojas-Bracho L, López-Villegas MT, Vadillo-Ortega F, De Vizcaya-Ruiz A, Rosas Perez I, O'Neill MS, Osornio-Vargas AR. 2016. TNFα and IL-6 responses to particulate matter in vitro: variation according to PM size, season, and polycyclic aromatic hydrocarbon and soil content. Environ Health Perspect 124:406-412; http://dx.doi.org/10.1289/ehp.1409287.

The potential role of prolactin as a modulator of the secretion of proinflammatory mediators in chorioamniotic membranes in term human gestation.

OBJECTIVE: To test the effect of prolactin (PRL) on expression of proinflammatory cytokines and matrix metallopeptidase 9 (MMP-9) in vitro. STUDY DESIGN: Tissue explants were incubated from 4 to 48 hours alone or in the presence of 500 ng/mL PRL, and mRNA expression in tissues and secretion of interleukin (IL)-1ß, tumor necrosis factor alpha (TNF-α), MMP-2, and MMP-9 was quantified. RESULTS: Fetal membranes secreted IL-1ß, TNF-α, and MMP-9 in culture with consistent low concentration during the first 24 hours and then increased progressively. The presence of PRL during explant incubation significantly decreased the patterns of IL-1ß, TNF-α and MMP-9 secretion along culture (P < .001). MMP-2 secretion was unaffected by PRL. The relative basal expression of IL-1ß mRNA (1.2 ± 0.87) was reduced by 80% in the presence of PRL after 32 hours of incubation of the membranes (P = .001). The expression of the TNF-α mRNA was not modified by the presence of PRL (0.06 ± 0.01) compared with the basal expression levels (0.05 ± 0.01). MMP-9 mRNA basal expression (0.018 ± 0.008) was significantly reduced (P = .001) in the presence of PRL after 32 hours (0.002 ± 0.0005). CONCLUSION: PRL may be a potential candidate as a key signal controlling the expression of signals related to the proinflammatory reaction associated with human labor.

[Association between adiposity, inflammation and cardiovascular risk factors in school-aged Mexican children]. / Asociación entre adiposidad, inflamación y factores de riesgo cardiovascular en un grupo de escolares mexicanos.

OBJECTIVE: To evaluate the differences in inflammation markers and cardiovascular risk factors in a group of school-aged children with and without excessive adiposity. To examine the relationship between adiposity, inflammation, and cardiovascular risk factors. METHODS: Cross-sectional study of 285 school children (8-12 years old). Adiposity (body mass index, BMI, total body fat, TBF, and waist circumference), inflammatory markers (C-reactive protein [CRP], interleukin 1ß [IL-1ß], interleukin 6 [IL-6], and tumor necrosis factor-a [TNF-α]) and cardiovascular risk factors were analyzed. Mean differences were calculated and multiple regression models were made. RESULTS: Obese children had higher concentrations of CRP and IL-1ß; children with abdominal obesity also had higher CRP levels. A higher BMI was associated with higher blood pressure, and higher total cholesterol, triglycerides-TAG, and insulin concentrations, and with lower HDL-cholesterol. The CRP and IL-1ß concentrations correlated significantly with the three adiposity indices. The IL-6 concentrations were associated with TAG, and IL-1ß with HDL-cholesterol concentration, after adjustment by BMI. DISCUSSION: In a group of school-aged Mexican children, obesity increases cardiovascular risk and inflammation. Both IL-6 and IL-1ß appear to be factors involved in lipid alterations in these children. More research is needed in order to explore the role of subclinical inflammation in the development of cardiovascular alterations that have already been described in Mexican children with obesity.

Variation in the composition and in vitro proinflammatory effect of urban particulate matter from different sites.

Spatial variation in particulate matter-related health and toxicological outcomes is partly due to its composition. We studied spatial variability in particle composition and induced cellular responses in Mexico City to complement an ongoing epidemiologic study. We measured elements, endotoxins, and polycyclic aromatic hydrocarbons in two particle size fractions collected in five sites. We compared the in vitro proinflammatory response of J774A.1 and THP-1 cells after exposure to particles, measuring subsequent TNFα and IL-6 secretion. Particle composition varied by site and size. Particle constituents were subjected to principal component analysis, identifying three components: C(1) (Si, Sr, Mg, Ca, Al, Fe, Mn, endotoxin), C(2) (polycyclic aromatic hydrocarbons), and C(3) (Zn, S, Sb, Ni, Cu, Pb). Induced TNFα levels were higher and more heterogeneous than IL-6 levels. Cytokines produced by both cell lines only correlated with C(1) , suggesting that constituents associated with soil induced the inflammatory response and explain observed spatial differences.

Specific inflammatory microenvironments in the zones of the fetal membranes at term delivery.

OBJECTIVE: The purpose of this study was to examine the histologic and immunologic differences between fetal membrane zones after membrane rupture at term delivery. STUDY DESIGN: Fetal membrane explants from postrupture zones (periplacental, middle, rupture) were obtained from women following spontaneous vaginal delivery at term (n = 5). Tissues for histology, protein extracts, and RNA were isolated. RESULTS: The collagen distribution decreased and the leukocyte density increased from the periplacental zone to the rupture zone. T cells were mainly present in the rupture zone and granulocytes in the middle zone. CXCL10, CXCR1, ICAM-1, -2, PSEL, tumor necrosis factor alpha, and matrix metalloproteinase-9 levels were higher in the middle zone than in the rupture zone and periplacental zone (P < .021). Interleukin-1beta and CXCL8 levels were higher in the rupture zone than in the middle zone and periplacental zone (P = .018 and P < .0001). CONCLUSION: During labor specific immunologic microenvironments are created in the zones of the fetal membrane that may be involved in their rupture at the end of gestation.

Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial.

OBJECTIVE: To test the hypothesis that a relative deficiency in L-arginine, the substrate for synthesis of the vasodilatory gas nitric oxide, may be associated with the development of pre-eclampsia in a population at high risk. DESIGN: Randomised, blinded, placebo controlled clinical trial. SETTING: Tertiary public hospital in Mexico City. PARTICIPANTS: Pregnant women with a history of a previous pregnancy complicated by pre-eclampsia, or pre-eclampsia in a first degree relative, and deemed to be at increased risk of recurrence of the disease were studied from week 14-32 of gestation and followed until delivery. INTERVENTIONS: Supplementation with a medical food-bars containing L-arginine plus antioxidant vitamins, antioxidant vitamins alone, or placebo-during pregnancy. MAIN OUTCOME MEASURE: Development of pre-eclampsia/eclampsia. RESULTS: 222 women were allocated to the placebo group, 228 received L-arginine plus antioxidant vitamins, and 222 received antioxidant vitamins alone. Women had 4-8 prenatal visits while receiving the bars. The incidence of pre-eclampsia was reduced significantly (χ(2) = 19.41; P < 0.001) in women randomised to L-arginine plus antioxidant vitamins compared with placebo (absolute risk reduction 0.17 (95% confidence interval 0.12 to 0.21). Antioxidant vitamins alone showed an observed benefit, but this effect was not statistically significant compared with placebo (χ(2) = 3.76; P = 0.052; absolute risk reduction 0.07, 0.005 to 0.15). L-arginine plus antioxidant vitamins compared with antioxidant vitamins alone resulted in a significant effect (P = 0.004; absolute risk reduction 0.09, 0.05 to 0.14). CONCLUSIONS: Supplementation during pregnancy with a medical food containing L-arginine and antioxidant vitamins reduced the incidence of pre-eclampsia in a population at high risk of the condition. Antioxidant vitamins alone did not have a protective effect for prevention of pre-eclampsia. Supplementation with L-arginine plus antioxidant vitamins needs to be evaluated in a low risk population to determine the generalisability of the protective effect, and the relative contributions of L-arginine and antioxidant vitamins to the observed effects of the combined treatment need to be determined. Trial registration Clinical trials NCT00469846.

The effect of exercise on cardiovascular risk markers in Mexican school-aged children: comparison between two structured group routines / Efecto del ejercicio sobre marcadores de riesgo cardiovascular en escolares mexicanos: comparación entre dos rutinas grupales

Objective. To assess the effects of two groups of exercise routines on cardiovascular disease risk markers. Material and Methods. An intervention study was conducted with 319 Mexican school-aged children in which routines were implemented Monday through Friday for 12 weeks. Routine A was the reference group, with 20 min of less intense activity and routine B was the new group with 40 min of aerobic exercises. Body mass index (BMI), waist circumference, fat mass percentage (FM percent), systolic and diastolic blood pressure, lipids, lipoproteins, glucose and insulin were measured before and after the intervention. Results. Routine A had an effect on diastolic pressure, while routine B had an effect on BMI, FM percent, blood pressure and triglycerides. Routine B had a greater effect on blood pressure than routine A. The prevalence of obesity, high blood pressure and hypertriglyceridemia decreased in both groups. Conclusion. Aerobic exercise is an effective health promotion strategy to reduce some cardiovascular disease risk markers.

Objetivo. Evaluar el efecto de dos rutinas grupales de ejercicio sobre marcadores de riesgo cardiovascular. Material y métodos. Intervención en 319 escolares mexicanos. Las rutinas fueron implementadas por 12 semanas (rutina A (referencia): 20 min con ejercicios menos intensos vs rutina B (nueva): 40 min con ejercicios aeróbicos). Se midieron al inicio y al final el índice de masa corporal (IMC), masa grasa ( por cientoMG), presión arterial sistólica y diastólica, lípidos, lipoproteínas, glucosa e insulina. Resultados. La rutina A tuvo efecto sobre la presión diastólica; la B tuvo efecto sobre el IMC, por cientoMG, presión arterial y triglicéridos. La rutina B tuvo mayores efectos en la presión arterial que la rutina A. Las prevalencias de obesidad, hipertensión arterial e hipertrigliceridemia disminuyeron en ambos grupos. Conclusiones. El ejercicio aeróbico es una estrategia de promoción exitosa para reducir algunos marcadores de riesgo cardiovascular.

Interaction between pathogenic bacteria and intrauterine leukocytes triggers alternative molecular signaling cascades leading to labor in women.

Increased risk of preterm labor has been linked to cervicovaginal infection with Ureaplasma urealyticum and group B streptococci. Although various experimental models have been developed to study the role of amniochorion infection in preterm labor, they typically exclude the initial interaction between intrauterine leukocytes (recruited from decidual vessels into the avascular fetal membranes) and infecting bacteria. In this work, we ascertained whether inflammatory molecules secreted by bacterium-activated intrauterine leukocytes stimulate the amniochorion production of mediators involved in human labor. Using a two-step process beginning with placental circulating leukocytes as a proxy for intrauterine leukocytes, we found that coincubation of amniochorion explants with plasma from placental whole blood preincubated with group B streptococci resulted in a significant increase in tumor necrosis factor alpha (TNF-α) and matrix metalloproteinase 9 (MMP-9) levels in tissue. Extensive changes in the connective tissue arrangement and a decrease in collagen content demonstrated the degradation of the extracellular matrix following this treatment. In contrast, plasma from blood preconditioned with U. urealyticum induced a highly significant secretion of interleukin-1ß (IL-1ß) and prostaglandin E(2) (PGE(2)) by the amniochorion without changes in the extracellular matrix organization or content. These data demonstrate that group B streptococci induce degradation of the amniochorion as a result of MMP-9 production, probably via TNF-α, whereas U. urealyticum stimulates the secretion of PGE(2), probably via IL-1ß, potentially stimulating myometrial contraction. Our study provides novel evidence that the immunological cells circulating within the uterine microenvironment respond differentially to an infectious agent, triggering alternative molecular signaling pathways leading to human labor.

Placental blood leukocytes are functional and phenotypically different than peripheral leukocytes during human labor.

Rupture of the fetal membranes during human labor is associated with an inflammatory process localized to the maternal-fetal interface. There is evidence that specific leukocytes subsets are attracted to the choriodecidua, and that after homing they condition a local inflammatory microenvironment, possibly being directly involved in rupture of the membranes. In this study our aim was to compare the phenotypes and function of leukocytes located in the placental intervillous blood with peripheral leukocytes obtained before or after labor, including expression of modulators of inflammation in these cells. Flow cytometry revealed that the proportion of CD14(+) cells is increased in intervillous blood, suggesting the participation of monocytes/macrophages during labor. Real time qRT-PCR showed that at term gestation and particularly during labor, placental blood leukocytes adopt a different expression pattern of pro-inflammatory cytokines than leukocytes in peripheral blood, including IL-1beta and IL-1RA. During labor, both placental and peripheral leukocytes increase their secretion of matrix metalloproteinase-9. Moreover, we showed that placental leukocytes respond differently than peripheral leukocytes to bacterial lipopolysaccharide, secreting differential amounts of TNF-alpha, IL-1beta and IL-6. Finally, a preliminary proteomic characterization of placental leukocytes revealed a significantly higher number of individual proteins than in peripheral leukocytes. Our results support the existence of selective subsets of leukocytes recruited to the maternal-fetal interface that may participate in the triggering of parturition.