Homogeneidad genética en mujeres con cáncer de mama en el noreste de México

Propósito y Método de Estudio: El cáncer de mama (CM) es la segunda neoplasia maligna más frecuente en México y es la primera causa de muerte por neoplasia en mujeres de Nuevo León. Aunque existen estudios en el Noreste de México que han probado homogeneidad genética en población aleatoria con el estudio de grupos sanguíneos, DNAmt y marcadores polimórficos del tipo de D1S80 y HLA-DQAl, es muy importante determinar si existe homogeneidad genética no solo en la población general, sino también en la población con cáncer. En este trabajo se determinó si existe homogeneidad genética en mujeres con cáncer de mama en una muestra de 115 mujeres con CM y 143 individuos de población general. Se utilizaron tres marcadores polimórficos del tipo STRs y se comparó la estructura genética de estas poblaciones seleccionadas versus la estructura genética de un estudio previo en población aleatoria en el Noreste de México. Para la realización de este trabajo se montó y estandarizó la técnica para obtención de DNA, amplificación de los STRs y detección de los polimorfismos mediante electroforesis en gel de poliacrilamida y revelado con plata. Contribuciones y conclusiones: Las frecuencias génicas de los tres STRs para las poblaciones con y sin CM estuvieron en equilibrio de Hardy-Weinberg. Para los 3 STRs (D16S539, D7S820 y D13S317): 1) las heterocigocidades observadas (esperadas) fueron 0.77 (0.78), 0.77 (0.77) y 0.80 (0.80) para CM y 0.76 (0.77), 0.78 (0.78) y 0.81 (0.81) para la población general, 2) las PDs fueron 0.90, 0.91 y 0.92 para CM y 0.89, 0.91 y 0.93 para la población general y 3) las PEs fueron 0.56, 0.55 y 0.61 para CM y 0.55, 0.57 y 0.63 para la población general. Las comparaciones de las frecuencias alélicas y genotípicas entre las poblaciones con y sin CM no fueron significativas. Las contribuciones caucásicas, indígena y africana para la población: 1) CM: 32%, 59% y 9%, 2) General: 45%, 54% y 1%, 3) Hispanos: 44%, 55% y 1% y 4) Honduras: 24%, 59% y 17%. Las comparaciones entre CM, población general e Hispanos no mostraron diferencias significativas entre ellas pero si con la población de Honduras al aplicarse la prueba de Rao. El análisis de componentes principales explicó un 98% de la variabilidad ubicando a las poblaciones en un plano similar, e intermedio a las poblaciones ancestrales caucásicas e indígenas y mínimamente a la africana.. Estos resultados apoyan la hipótesis propuesta en el presente estudio. La demostración de homogeneidad genética en esta población seleccionada con CM indica que esta población es adecuada para 1) realizar estudios de marcadores genéticos asociados con la enfermedad en la búsqueda de genes candidatos y 2) de farmacogenómica. Abstract Purpose and Study Methods : Breast cancer (BC) is the second most frequent Malignant neoplasia in Mexico and the first neoplastic cause of death in women at Nuevo Leon. Although there are studies in the Northeast Mexico that had proved genetic homogeneity in aleatory population using blood groups, DNAmt and polymorphic markers such as D1S80 and HLA-DQA1, it is very important to establish if there is genetic homogeneity not only in general population, but also in cancer population. In this work we determined if there was genetic homogeneity in women with breast cancer in a sample of 115 women with BC and 143 healthy individuals. Three polymorphic STR type markers were used and the genetic structure of the selected population was compared with one of a previous study in aleatory population in Northeast Mexico. The techniques employed included DNA obtainment, STRs amplification, and detection of polymorphisms with polyacrilamide gel electrophoresis and silver staining. Contributions and conclusions: The genetic frequencies of the three STRs for the populations with and without BC were in equilibrium of Hardy-Weinberg. For the 3 STRs (D16S539, D7S820 y D13S317): 1) Observed heterocigocity (expected) were 0.77 (0.78), 0.77 (0.77) and 0.80 (0.80) for BC and 0.76 (0.77), 0.78 (0.78) and 0.81 (0.81) for the general population, 2) The DPs were 0.90, 0.91 and 0.92 for BC and 0.89, 0.91 and 0.93 for general population 3) The EPs were 0.56, 0.55 and 0.61 for BC and 0.55, 0.57 and 0.63 for general population. The comparison of allelic and genotypic frequencies between populations with and without BC was not significant. The Caucasian, Indian and African contributions for the population, were: 1) BC: 32%, 59% y 9%, 2) General: 45%, 54% y 1%, 3) Hispanics: 44%, 55% y 1% y 4) Honduras: 24%, 59% y 17%. Comparisons between BC, general populations and Hispanics did not show significative differences among them, but were evident with the Honduras population with the Rao test. The component analysis explained 98% of the variability, locating the populations in a similar plane, and in the middle way respecting to the Caucasian and Indian ancestries and in minor degree with the African one. These results support the proposed hypothesis in this study. The demonstration of genetic homogeneity in this selected BC population indicates that this population is adequate for: 1) Search BC candidate genes and 2) Research in pharmacogenomics

Búsqueda de las mutaciones mas frecuentes del Gen Brca 1 en pacientes con cáncer de mama, en el Noreste de México

Tesis (Maestría en Ciencias con Especialidad en Biología Molecular e Ingeniería Genética) UANLUANLhttp://www.uanl.mx

Air pollution, a rising environmental risk factor for cognition, neuroinflammation and neurodegeneration: The clinical impact on children and beyond

International audienceAir pollution (indoors and outdoors) is a major issue in public health as epidemiological studies have highlighted its numerous detrimental health consequences (notably, respiratory and cardiovascular pathological conditions). Over the past 15 years, air pollution has also been considered a potent environmental risk factor for neurological diseases and neuropathology. This review examines the impact of air pollution on children's brain development and the clinical, cognitive, brain structural and metabolic consequences. Long-term potential consequences for adults’ brains and the effects on multiple sclerosis (MS) are also discussed. One challenge is to assess the effects of lifetime exposures to outdoor and indoor environmental pollutants, including occupational exposures: how much, for how long and what type. Diffuse neuroinflammation, damage to the neurovascular unit, and the production of autoantibodies to neural and tight-junction proteins are worrisome findings in children chronically exposed to concentrations above the current standards for ozone and fine particulate matter (PM2.5), and may constitute significant risk factors for the development of Alzheimer's disease later in life. Finally, data supporting the role of air pollution as a risk factor for MS are reviewed, focusing on the effects of PM10 and nitrogen oxide

Combustion-Derived Nanoparticles, the Neuroenteric System, Cervical Vagus, Hyperphosphorylated Alpha Synuclein and Tau in Young Mexico City Residents

Mexico City (MC) young residents are exposed to high levels of fine particulate matter (PM2.5), have high frontal concentrations of combustion-derived nanoparticles (CDNPs), accumulation of hyperphosphorylated aggregated α-synuclein (α-Syn) and early Parkinson\u27s disease (PD). Swallowed CDNPs have easy access to epithelium and submucosa, damaging gastrointestinal (GI) barrier integrity and accessing the enteric nervous system (ENS). This study is focused on the ENS, vagus nerves and GI barrier in young MC v clean air controls. Electron microscopy of epithelial, endothelial and neural cells and immunoreactivity of stomach and vagus to phosphorylated ɑ-synuclein Ser129 and Hyperphosphorylated-Tau (Htau) were evaluated and CDNPs measured in ENS. CDNPs were abundant in erythrocytes, unmyelinated submucosal, perivascular and intramuscular nerve fibers, ganglionic neurons and vagus nerves and associated with organelle pathology. ɑSyn and Htau were present in 25/27 MC gastric,15/26 vagus and 18/27 gastric and 2/26 vagus samples respectively. We strongly suggest CDNPs are penetrating and damaging the GI barrier and reaching preganglionic parasympathetic fibers and the vagus nerve. This work highlights the potential role of CDNPs in the neuroenteric hyperphosphorylated ɑ-Syn and tau pathology as seen in Parkinson and Alzheimer\u27s diseases. Highly oxidative, ubiquitous CDNPs constitute a biologically plausible path into Parkinson\u27s and Alzheimer\u27s pathogenesis

Early Alzheimer\u27s and Parkinson\u27s Disease Pathology in Urban Children: Friend versus Foe Responses—It Is Time to Face the Evidence

Chronic exposure to particulate matter air pollution is known to cause inflammation leading to respiratory- and cardiovascularrelated sickness and death. Mexico City Metropolitan Area children exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, and innate and adaptive immune responses. Early dysregulated neuroinflammation, brain microvascular damage, production of potent vasoconstrictors, and perturbations in the integrity of the neurovascular unit likely contribute to progressive neurodegenerative processes. The accumulation of misfolded proteins coincides with the anatomical distribution observed in the early stages of both Alzheimer\u27s and Parkinson\u27s diseases. We contend misfolding of hyperphosphorylated tau (HPrc), alpha-synuclein, and beta-amyloid could represent a compensatory early protective response to the sustained systemic and brain inflammation. However, we favor the view that the chronic systemic and brain dysregulated inflammation and the diffuse vascular damage contribute to the establishment of neurodegenerative processes with childhood clinical manifestations. Friend turns Foe early; therefore, implementation of neuroprotective measures to ameliorate or stop the inflammatory and neurodegenerative processes is warranted in exposed children. Epidemiological, cognitive, structural, and functional neuroimaging and mechanistic studies into the association between air pollution exposures and the development of neuroinflammation and neurodegeneration in children are of pressing importance for public health

PERFIL BIO-PSICO-SOCIAL DE ADOLESCENTES CON CONDUCTA DELICTIVA EN EL ESTADO DE NUEVO LEON, MEXICO

Comparar el perfil bio-psico-social  de dos grupos de  adolescentes con conducta agresiva delictiva. Se incluyeron el grupo de menores que cometieron homicidio (n = 42) y una muestra aleatoria (n = 42) de los que cometieron robo en un lapso de 4 años en el estado de Nuevo León. Se analizaron 24 variables. El análisis estadístico consistió en X2, razón de momios y regresión logística múltiple. La comparación entre los dos grupos reveló preponderancia en el tabaquismo (p= 0.008, RM 2.96), ingesta de  bebidas alcohólicas (p = 0.01, RM 4.11), disfunción familiar (p= 0.015, RM 3.4), enfermedad cerebral (p = 0.046, RM 2.45) entre los adolescentes que cometieron homicidio. El modelo más explicativo incluyó las tres primeras variables mencionadas  (X2= 19.69, R2= 0.16, p=  0.0002). Los homicidios ocurrieron predominantemente durante la noche (p=  0.001, RM 3.6) y estos adolescentes  presentaron deprivación crónica parcial de sueño nocturno. Conclusiones: Los hábitos personales y la dinámica familiar son importantes en estos grupos y revelan un área de oportunidad que debe ser atendida por las Instituciones correspondientes y por la Sociedad; mientras tanto, el respetar los períodos fisiológicos de sueño puede emerger como medida preventiva contra la máxima expresión de agresividad en adolescentes. Abstract To  compare the biophycosocial profile of adolescents with aggressive offending behavior. The group of adolescents (n= 42) who committed homicide and a random sample (n = 42) of robbery cases  during a 4 years period in Nuevo Leon state were included. 24 variables were studied. X2, odd ratios and logistic regression analysis were performed. Comparison  between groups reveled preponderance in tobacco habit (p= 0.008, OR 2.96), alcoholic beverage consumption (p = 0.01, OR 4.11), family dysfunction  (p= 0.015, OR 3.4), and cerebral disease (p = 0.046, OR 2.45) among adolescents who committed homicide. The most explicative model included the first three variables  (X2= 19.69, R2= 0.16, p=  0.0002). Homicides were predominantly during the night (p=  0.001, OR 3.6) and these adolescents showed chronic partial nocturnal sleep deprivation. Conclusions: Personal habits and family functionality are important in these groups and reveal an opportunity area that  should be attended by the correspondent Institutions and by Society. In the mean time, the accomplishment of the physiological sleep periods may emerge as a preventive effort against the maximal expression of aggressive behavior. Palabras clave: Adolescentes,  agresividad, perfil,  deprivación de sueño, sleep deprivation

Elevated Plasma Endothelin-1 and Pulmonary Arterial Pressure in Children Exposed to Air Pollution

BackgroundControlled exposures of animals and humans to particulate matter (PM) or ozone air pollution cause an increase in plasma levels of endothelin-1, a potent vasoconstrictor that regulates pulmonary arterial pressure.ObjectivesThe primary objective of this field study was to determine whether Mexico City children, who are chronically exposed to levels of PM and O3 that exceed the United States air quality standards, have elevated plasma endothelin-1 levels and pulmonary arterial pressures.MethodsWe conducted a study of 81 children, 7.9 ± 1.3 years of age, lifelong residents of either northeast (n = 19) or southwest (n = 40) Mexico City or Polotitlán (n = 22), a control city with PM and O3 levels below the U.S. air quality standards. Clinical histories, physical examinations, and complete blood counts were done. Plasma endothelin-1 concentrations were determined by immunoassay, and pulmonary arterial pressures were measured by Doppler echocardiography.ResultsMexico City children had higher plasma endothelin-1 concentrations compared with controls (p < 0.001). Mean pulmonary arterial pressure was elevated in children from both northeast (p < 0.001) and southwest (p < 0.05) Mexico City compared with controls. Endothelin-1 levels in Mexico City children were positively correlated with daily outdoor hours (p = 0.012), and 7-day cumulative levels of PM air pollution < 2.5 μm in aerodynamic diameter (PM2.5) before endothelin-1 measurement (p = 0.03).ConclusionsChronic exposure of children to PM2.5 is associated with increased levels of circulating endothelin-1 and elevated mean pulmonary arterial pressure

Translocation and potential neurological effects of fine and ultrafine particles a critical update

ABSTRACT: Particulate air pollution has been associated with respiratory and cardiovascular disease. Evidence for cardiovascular and neurodegenerative effects of ambient particles was reviewed as part of a workshop. The purpose of this critical update is to summarize the evidence presented for the mechanisms involved in the translocation of particles from the lung to other organs and to highlight the potential of particles to cause neurodegenerative effects.Fine and ultrafine particles, after deposition on the surfactant film at the air-liquid interface, are displaced by surface forces exerted on them by surfactant film and may then interact with primary target cells upon this displacement. Ultrafine and fine particles can then penetrate through the different tissue compartments of the lungs and eventually reach the capillaries and circulating cells or constituents, e.g. erythrocytes. These particles are then translocated by the circulation to other organs including the liver, the spleen, the kidneys, the heart and the brain, where they may be deposited. It remains to be shown by which mechanisms ultrafine particles penetrate through pulmonary tissue and enter capillaries. In addition to translocation of ultrafine particles through the tissue, fine and coarse particles may be phagocytized by macrophages and dendritic cells which may carry the particles to lymph nodes in the lung or to those closely associated with the lungs. There is the potential for neurodegenerative consequence of particle entry to the brain. Histological evidence of neurodegeneration has been reported in both canine and human brains exposed to high ambient PM levels, suggesting the potential for neurotoxic consequences of PM-CNS entry. PM mediated damage may be caused by the oxidative stress pathway. Thus, oxidative stress due to nutrition, age, genetics among others may increase the susceptibility for neurodegenerative diseases. The relationship between PM exposure and CNS degeneration can also be detected under controlled experimental conditions. Transgenic mice (Apo E -/-), known to have high base line levels of oxidative stress, were exposed by inhalation to well characterized, concentrated ambient air pollution. Morphometric analysis of the CNS indicated unequivocally that the brain is a critical target for PM exposure and implicated oxidative stress as a predisposing factor that links PM exposure and susceptibility to neurodegeneration.Together, these data present evidence for potential translocation of ambient particles on organs distant from the lung and the neurodegenerative consequences of exposure to air pollutants