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Chronic inflammation and infection are major risk factors for gastric carcinogenesis in adults. As chronic gastritis is common in Mexican children, diagnosis of Helicobacter pylori and other causes of gastritis are critical for the identification of children who would benefit from closer surveillance. Antral biopsies from 82 Mexican children (mean age 8.3±4.8y) with chronic gastritis (36 H. pylori +, 46 H. pylori -) were examined for gastritis activity, atrophy, intestinal metaplasia, and immunohistochemical expression of gastric carcinogenesis biomarkers CDX2, ephrin type-B receptor 4, matrix metalloproteinase 3 (MMP3), macrophage migration inhibitory factor (MIF), p53, β-catenin, and E-cadherin. Atrophy was diagnosed in 7/82 (9%) and intestinal metaplasia in 5/82 (6%) by routine histology, while 6 (7%) additional children (3 H. pylori +) exhibited aberrant CDX2 expression without intestinal metaplasia. Significant positive correlations were seen between EphB4, MMP3, and MIF (p

Air pollution is a complex mixture of gases (e.g., ozone), particulate matter, and organic compounds present in outdoor and indoor air. Dogs exposed to severe air pollution exhibit chronic inflammation and acceleration of Alzheimer's-like pathology, suggesting that the brain is adversely affected by pollutants. We investigated whether residency in cities with high levels of air pollution is associated with human brain inflammation. Expression of cyclooxygenase-2 (COX2), an inflammatory mediator, and accumulation of the 42-amino acid form of β-amyloid (A β42), a cause of neuronal dysfunction, were measured in autopsy brain tissues of cognitively and neurologically intact lifelong residents of cities having low (n:9) or high (n:10) levels of air pollution. Genomic DNA apurinic/apyrimidinic sites, nuclear factor- κB activation and apolipoprotein E genotype were also evaluated. Residents of cities with severe air pollution had significantly higher COX2 expression in frontal cortex and hippocampus and greater neuronal and astrocytic accumulation of A β42 compared to residents in low air pollution cities. Increased COX2 expression and A β42 accumulation were also observed in the olfactory bulb. These findings suggest that exposure to severe airpollution is associated with brain inflammation and A β 42 accumulation, two causes of neuronal dysfunction that precede the appearance of neuritic plaques and neurofibrillary tangles, hallmarks of Alzheimer's disease.

Mexico City Metropolitan Area children chronically exposed to high concentrations of air pollutants exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, innate and adaptive immune responses along with accumulation of misfolded proteins observed in the early stages of Alzheimer and Parkinson's diseases. A complex modulation of serum cytokines and chemokines influences children's brain structural and gray/white matter volumetric responses to air pollution. The search for biomarkers associating systemic and CNS inflammation to brain growth and cognitive deficits in the short term and neurodegeneration in the long-term is our principal aim. We explored and compared a profile of cytokines, chemokines (Multiplexing LASER Bead Technology) and Cellular prion protein (PrP(C)) in normal cerebro-spinal-fluid (CSF) of urban children with high vs. low air pollution exposures. PrP(C) and macrophage inhibitory factor (MIF) were also measured in serum. Samples from 139 children ages 11.91 ± 4.2 years were measured. Highly exposed children exhibited significant increases in CSF MIF (p = 0.002), IL6 (p = 0.006), IL1ra (p = 0.014), IL-2 (p = 0.04), and PrP(C) (p = 0.039) vs. controls. MIF serum concentrations were higher in exposed children (p = 0.009). Our results suggest CSF as a MIF, IL6, IL1Ra, IL-2, and PrP(C) compartment that can possibly differentiate air pollution exposures in children. MIF, a key neuro-immune mediator, is a potential biomarker bridge to identify children with CNS inflammation. Fine tuning of immune-to-brain communication is crucial to neural networks appropriate functioning, thus the short and long term effects of systemic inflammation and dysregulated neural immune responses are of deep concern for millions of exposed children. Defining the linkage and the health consequences of the brain / immune system interactions in the developing brain chronically exposed to air pollutants ought to be of pressing importance for public health.

Mexico City Metropolitan Area children and young adults exposed to high concentrations of air pollutants including fine and ultrafine particulate matter (PM) vs. clean air controls, exhibit myocardial inflammation and inflammasome activation with a differential right and left ventricular expression of key inflammatory genes and inflammasomes. We investigated the mRNA expression levels of the prion protein gene PRNP, which plays an important role in the protection against oxidative stress and metal toxicity, and the glucose regulated protein 78, a key protein in endoplasmic reticulum (ER) stress signaling, in ventricular autopsy samples from 30 children and young adults age 19.97 ± 6.8 years with a lifetime of low (n:4) vs. high (n:26) air pollution exposures. Light microscopy and transmission electron microscopy studies were carried out in human ventricles, and electron microscopy studies were also done in 5 young, highly exposed Mexico City dogs. There was significant left ventricular PRNP and bi-ventricular GRP78 mRNA up-regulation in Mexico City young urbanites vs. controls. PRNP up-regulation in the left ventricle was significantly different from the right, p < 0.0001, and there was a strong left ventricular PRNP and GRP78 correlation (p = 0.0005). Marked abnormalities in capillary endothelial cells, numerous nanosized particles in myocardial ER and in abnormal mitochondria characterized the highly exposed ventricles. Early and sustained cardiac ER stress could result in detrimental irreversible consequences in urban children, and while highly complex systems maintain myocardial homeostasis, failure to compensate for chronic myocardial inflammation, oxidative and ER stress, and particles damaging myocardial organelles may prime the development of pathophysiological cardiovascular states in young urbanites. Nanosized PM could play a key cardiac myocyte toxicity role.

ResumenIntroducciónEl cáncer es la tercera causa de muerte en México; es la segunda causa de mortalidad por tumores malignos y su incidencia no ha disminuido en las últimas décadas.Material y métodoEntre el 1 de mayo de 2011 y el 2 de marzo de 2015, se incluyeron pacientes quienes, por sospecha clínica de lesión tumoral primaria, gástrica, fueron estudiados por endoscopia y TC con cualquier protocolo, obteniéndose el diagnóstico histopatológico tanto del gástrico primario como otros diagnósticos alternos.ResultadosParticiparon 45 pacientes, 28 masculinos (62%), 17 femeninos (38%). Las edades fluctuaron entre los 32 y los 86 años. El motivo clínico más frecuente correspondió a síndrome consuntivo solo o asociado a otros datos clínicos en 18 pacientes (40%); en 30 (66%) se corroboró cáncer gástrico por histopatología, en 16 (53%) la actividad tumoral se detectó en forma tardía, con carcitomatosis peritoneal en 13 (43%), 3 de ellos con metástasis hepáticas y uno de ellos con trombosis venosa; 2 con metástasis hepáticas y uno de ellos con trombosis venosa. En 12 pacientes (27%), se realizó la gastro-TC con o sin inclusión de tórax contrastado. El hallazgo de engrosamiento de pliegues gástricos se detectó en el 20%, con engrosamiento gástrico concéntrico en el 48% y asociado a lesión ulcerada, carcitomatosis peritoneal, metástasis hepáticas y trombosis venosa en un 32%. Ningún paciente fue detectado en forma temprana.ConclusionesLa distensión gástrica es crítica, y la gastro-TC representa la técnica ideal para la estadificación del cáncer gástrico. La asociación entre el síndrome consuntivo y el cáncer gástrico alcanzó un porcentaje elevado, siendo recomendable el abordaje diagnóstico con gastro-TC.AbstractIntroductionCancer is the third cause of death in Mexico, and is the second cause of malignant tumour-related mortality, with an incidence that has not declined over the last decades.Material and MethodsThe study included patients who were studied by endoscopy and CT using any protocol due to clinical suspicion of primary gastric tumour lesion in the period from 1 May 2011 to 2 March 2015. Primary gastric tumour diagnosis, as well as other alternative diagnoses, was established by histopathology.ResultsThe study included 45 patients, of whom, 28 were male (62%) and 17 were female (38%). Ages ranged from 32 to 86 years. The most common clinical reason was constitutional syndrome, either alone or associated with other clinical symptoms in 18 patients (40%). The gastric cancer was histopathologically confirmed in 30 patients (66%), with 16 (53%) being detected late, with peritoneal carcinomatosis (PC) in 13 (43%), 3 of them with liver metastasis (LM), 1 with venous thrombosis (VT), 2 with LM, and 1 with VT. The gastric CT protocol, with and without contrast-enhanced thoracic images, was performed in 12 patients (27%). Gastric folds thickening was detected in 20%, with concentric gastric thickening in 48% and associated with an ulcerated lesion, PC, LM and VT in 32%. No patients were detected early.ConclusionsGastric distension is critical in abdominal imaging and gastric CT represents the ideal imaging technique for gastric cancer staging and classification. The association between constitutional syndrome and gastric cancer reached an elevated rate, with gastric CT being recommendable for the diagnostic approach.