RESUMEN
Maternal exposure to stress during pregnancy is associated with an increased risk of psychiatric disorders in the offspring in later life. The mechanisms through which the effects of maternal stress are transmitted to the fetus are unclear, however the placenta, as the interface between mother and fetus, is likely to play a key role. Using a rat model, we investigated a role for placental oxidative stress in conveying the effects of maternal social stress to the fetus and the potential for treatment using a nanoparticle-bound antioxidant to prevent adverse outcomes in the offspring. Maternal psychosocial stress increased circulating corticosterone in the mother, but not in the fetuses. Maternal stress also induced oxidative stress in the placenta, but not in the fetal brain. Blocking oxidative stress using an antioxidant prevented the prenatal stress-induced anxiety phenotype in the male offspring, and prevented sex-specific neurobiological changes, specifically a reduction in dendrite lengths in the hippocampus, as well as reductions in the number of parvalbumin-positive neurons and GABA receptor subunits in the hippocampus and basolateral amygdala of the male offspring. Importantly, many of these effects were mimicked in neuronal cultures by application of placental-conditioned medium or fetal plasma from stressed pregnancies, indicating molecules released from the placenta may mediate the effects of prenatal stress on the fetal brain. Indeed, both placenta-conditioned medium and fetal plasma contained differentially abundant microRNAs following maternal stress, and their predicted targets were enriched for genes relevant to nervous system development and psychiatric disorders. The results highlight placental oxidative stress as a key mediator in transmitting the maternal social stress effects on the offspring's brain and behavior, and offer a potential intervention to prevent stress-induced fetal programming of affective disorders.
RESUMEN
The aim of this investigation was to evaluate the prognostic factors in patients with differentiated thyroid carcinoma treated and followed for a long period of time. Patients and Method: The following prognostic variables: gender, age at diagnosis, goiter characteristics, histology, differentiation grades, tumor anatomical extension, lymph node and distant initial metastasis and post treatment evolution were studied in a historical cohort of thyroid carcinoma. Surgical treatment was subtotal and total thyroidectomy plus lymphatic cervical selective neck dissection. Radioiodine was employed en 59.2 percent and thyroid hormone replacement was used indefinitely. Kaplan Meyer analisis was employed to plot survival curves, log Rank test was used to establish the significance of each variable and square chi to determine differences among groups. Cox model was used to identify prognostic variables. Results: A group of 477 patients with differentiated thyroid carcinoma treated at the Hospital San Juan de Dios, from 1948 to 1992, were studied. Median survival rate was 87 percent at the end of observation period. Univariate analysis showed significant differences for age, tumor anatomical extension and histological grade on survival, for the entire serie. According to Cox model method, initial distant metastasis, age > 40 years, anatomical extension, tumor size > 10 mm, were determinant for unfavorable prognosis for the papillary cancer; distant metastasis, anatomical extension and age at the time of diagnosis were determinant for unfavorable prognosis for the follicular cancer. Conclusion: Overall survival was 87 percent. Distant metastasis at the time of diagnosis: age older than 40 years, anatomical extension and the size of the tumor were determinant of survival prognosis.
El objetivo de esta investigación fue estudiar la supervivencia y los factores del pronóstico del cáncer diferenciado del tiroides tratado y seguido por un período de observación prolongado. Pacientes y Método: En una cohorte histórica prospectiva de cáncer de tiroides diagnosticada por biopsia quirúrgica, se analizó las variables: género, edad en el momento del diagnóstico, semiología del bocio, histología, grado de diferenciación, extensión anatómica del tumor, la presencia de metástasis linfáticas y a distancia iniciales y la evolución post tratamiento como factores pronosticadores de la sobrevida de los pacientes. La cirugía practicada consistió en tiroidectomía sub total y total más disección linfática cervical selectiva. El método de Kaplan y Meier se usó para diseñar curvas de supervivencia, log Rank test para la significación de cada variable y chi cuadrado para definir la diferencias entre los grupos. El método de Cox se utilizó para identificar las variables del pronóstico. Resultados: 477 pacientes con cáncer diferenciado del tiroides tratados en el Hospital San Juan de Dios desde 1948 hasta 1992. El 59,2 por ciento recibió yodo 131, todos con tratamiento hormonal de frenación indefinidamente. La supervivencia media fue de 87 por ciento al final del período de observación. El análisis univariable demostró diferencias significativas para la edad, extensión anatómica y grado histológico. Determinan un pronóstico desfavorable para el cáncer papilar: las metástasis a distancia iniciales (p < 0,0001), la edad > de 40 años (p < 0,0018) y la extensión anatómica; en el cáncer folicular fueron las metástasis a distancia, extensión anatómica y la edad en el momento del diagnóstico. Conclusión: La supervivencia fue de 87 por ciento. Las variables metástasis a distancia en el momento del diagnóstico, edad mayor de 40 años, extensión anatómica y el tamaño del tumor fueron determinantes del pronóstico en la supervivencia de los pacientes.