Antral atrophy, intestinal metaplasia, and preneoplastic markers in Mexican children with Helicobacter pylori-positive and Helicobacter pylori-negative gastritis.

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 ± 4.8 years) with chronic gastritis (36 H pylori+, 46 H pylori-) were examined for gastritis activity, atrophy, intestinal metaplasia (IM), and immunohistochemical expression of gastric carcinogenesis biomarkers caudal type homeobox 2 (CDX2), ephrin type-B receptor 4 (EphB4), matrix metalloproteinase 3 (MMP3), macrophage migration inhibitory factor (MIF), p53, ß-catenin, and E-cadherin. Atrophy was diagnosed in 7 (9%) of 82, and IM, in 5 (6%) of 82 by routine histology, whereas 6 additional children (7%) (3 H pylori+) exhibited aberrant CDX2 expression without IM. Significant positive correlations were seen between EphB4, MMP3, and MIF (P<.0001). Atrophy and follicular pathology were more frequent in H pylori+ biopsies (P<.0001), whereas IM and CDX2 expression showed no significant correlation with H pylori status. Antral biopsies demonstrating atrophy, IM, and/or aberrant CDX2 expression were seen in 21.95% (18/82) of the children, potentially identifying those who would benefit from closer surveillance and preventive dietary strategies. Biomarkers CDX2, EphB4, MMP3, and MIF may be useful in the workup of pediatric gastritis.

Up-regulation of mRNA ventricular PRNP prion protein gene expression in air pollution highly exposed young urbanites: endoplasmic reticulum stress, glucose regulated protein 78, and nanosized particles.

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.

Brain immune interactions and air pollution: macrophage inhibitory factor (MIF), prion cellular protein (PrP(C)), Interleukin-6 (IL-6), interleukin 1 receptor antagonist (IL-1Ra), and interleukin-2 (IL-2) in cerebrospinal fluid and MIF in serum differentiate urban children exposed to severe vs. low air pollution.

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.

Flavonol-rich dark cocoa significantly decreases plasma endothelin-1 and improves cognition in urban children.

Air pollution exposures are linked to systemic inflammation, cardiovascular and respiratory morbidity and mortality, neuroinflammation and neuropathology in young urbanites. In particular, most Mexico City Metropolitan Area (MCMA) children exhibit subtle cognitive deficits, and neuropathology studies show 40% of them exhibiting frontal tau hyperphosphorylation and 51% amyloid-ß diffuse plaques (compared to 0% in low pollution control children). We assessed whether a short cocoa intervention can be effective in decreasing plasma endothelin 1 (ET-1) and/or inflammatory mediators in MCMA children. Thirty gram of dark cocoa with 680 mg of total flavonols were given daily for 10.11 ± 3.4 days (range 9-24 days) to 18 children (10.55 years, SD = 1.45; 11F/7M). Key metabolite ratios in frontal white matter and in hippocampus pre and during cocoa intervention were quantified by magnetic resonance spectroscopy. ET-1 significantly decreased after cocoa treatment (p = 0.0002). Fifteen children (83%) showed a marginally significant individual improvement in one or both of the applied simple short memory tasks. Endothelial dysfunction is a key feature of exposure to particulate matter (PM) and decreased endothelin-1 bioavailability is likely useful for brain function in the context of air pollution. Our findings suggest that cocoa interventions may be critical for early implementation of neuroprotection of highly exposed urban children. Multi-domain nutraceutical interventions could limit the risk for endothelial dysfunction, cerebral hypoperfusion, neuroinflammation, cognitive deficits, structural volumetric detrimental brain effects, and the early development of the neuropathological hallmarks of Alzheimer's and Parkinson's diseases.

Brain inflammation and Alzheimer's-like pathology in individuals exposed to severe air pollution.

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 beta-amyloid (Abeta42), 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-kappaB 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 Abeta42 compared to residents in low air pollution cities. Increased COX2 expression and Abeta42 accumulation were also observed in the olfactory bulb. These findings suggest that exposure to severe air pollution is associated with brain inflammation and Abeta42 accumulation, two causes of neuronal dysfunction that precede the appearance of neuritic plaques and neurofibrillary tangles, hallmarks of Alzheimer's disease.

Terapia combinada interferón alfa 2b-ribavirina en pacientes con hepatitis crónica por virus C. Informe de 15 casos / Combined therapy interferon alpha 2b plus ribavirin in patients with chronic hepatitis C. A 15 cases report

Antecedentes. La hepatitis C crónica cuya prevalencia mundial es de 0.4 a 13 por ciento, evolucionará en 80 a 85 por ciento de los casos a cronicidad con riesgo de 20-50 por ciento de cirrosis a 20 años e incidencia acumulada para cáncer hepático de 40 por ciento a siete años.El tratamiento con interferón alfa por seis meses tiene respuesta de 15 a 20 por ciento. Combinando interferón más ribavirina la respuesta aumenta tres veces.Objetivo. Conocer la respuesta al tratamiento combinando interferón alfa 2b más ribavirina por seis meses y seguimiento a un año en pacientes con hepatitis C crónica.Método. Durante el periodo de mayo 1999 a mayo del 2000 se estudiaron 15 pacientes con diagnóstico clínico e histológico de hepatitis crónica por virus C con índice histológico Knodell 4 a 6, elevación de transaminasas arriba de 1.5 veces el valor normal, antiVHC positivo por técnica de ELISA de segunda generación y PCR/carga viral positiva de virus C. Recibieron interferón alfa 2b 5 millones de unidades internacionales (UI) diarias por dos semanas, posteriormente interferón alfa tres millones UI tres veces por semana más rivabirina 15 mg/kg/seis meses. Se llevó a cabo evaluación de control al inicio, a los tres meses y a los seis meses. Pruebas de función hepática y biometría hemática al año.Resultados. Recibieron tratamiento 13 mujeres y dos hombres con edad promedio de 46 años, antecedente de hemotransfusión en 13 (87 por ciento) y contacto esporádico en dos (13 por ciento). En cinco (36 por ciento) se obtuvo desaparición de la carga viral, normalización de transaminasas y cambio histológico con índice Knodell de 0 a 2 al finalizar el tratamiento.El resto de los pacientes persistió con carga viral entre 1.3 x 10 genomas/mL a 2.9 x 10 genomas/mL e índice histológico Knodell 4.Los efectos colaterales en el 100 por ciento fueron alopecia parcial y depresión.Ningún paciente abandonó el tratamiento.El seguimiento a un año mostró carga viral en tres de los cinco pacientes con respuesta inicial al tratamiento, uno mostró elevación de carga viral y el último abandonó el seguimiento, el resto de los pacientes reinició tratamiento seis meses más con abandono del mismo de dos.Conclusión.El tratamiento combinado tuvo respuesta bioquímica, histológica y virológica en seis meses de 36 por ciento al presentarse alopecia parcial y labilidad emocional como efectos colaterales comunes que no propiciaron abandono del tratamiento.Las cifras de hemoglobina se mantuvieron normales.

Mujer de 58 años con diabetes, hipertensión y hemiparesia izquierda de inicio repentino / 58 years old woman with diabetes mellitus, hypertension and sudden left hemiplegia

Sesión clinicopatológica del 12 de mayo del 2001. Mujer de 58 años, con antecedentes de diabetes mellitus, hipertensión arterial, en el último año con depresión y abuso de alcohol posterior al fallecimiento de su esposo. Ingresó al hospital con hemiparesia izquierda y disartria de inicio repentino. El estudio de tomografía axial demostró hemorragia talámica derecha extendida a la región parahipocampal derecha y diseminación al sistema ventricular, con desplazamiento leve de la línea media a la izquierda, y evidencia de infartos lacunares pontinos antiguos. La paciente se hospitalizó en la unidad de cuidados intensivos y presentó deterioro progresivo de sus constantes hemodinámicas, así como de su condición neurológica. Evolucionó al estado de choque con edema pulmonar falleciendo finalmente. El estudio posmortem demostró la hemorragia cerebral y los infartos lacunares observados en la tomografía de cráneo, arteriosclerosis generalizada grado III-A con infarto cardiaco antiguo con hipertrofia del ventrículo izquierdo, trombos sépticos en la aurícula derecha, tromboembolia pulmonar como causa directa de la muerte, bronconeumonía y edema pulmonar, pielonefritis crónica, hígado graso secundario a alcoholismo, infiltración adiposa del páncreas, y un adenoma paratiroideo como hallazgo incidental. Se trata de un caso típico de complicaciones de enfermedades crónicas comunes

Recién nacido de tres días con tumor del muslo izquierdo / A three days old newborn with a tumor in his left thigh

Se presenta el caso discutido en la sesión clinicopatológica del 14 de julio de 2001 en el Hospital Central Militar. Se presentó el caso de un paciente recién nacido de tres días de edad con una lesión tumoral del muslo izquierdo; las radiografías iniciales mostraban una lesión lítica, destructiva, extracompartamental del fémur izquierdo, de características malignas. El diagnóstico se hizo mediante biopsia incisional, su manejo fue multidisciplinario mediante quimioterapia y cirugía. Se trata de un caso sumamente raro, de los cuales sólo se han informado 300 en la literatura mundial.