Arriazu Navarro, Riánsares

Childhood obesity is associated with metabolic and cardiovascular comorbidities. The development of these alterations may have its origin in early life stages such as the lactation period through metabolic programming. Insulin resistance is a common complication in obese patients and may be responsible for the cardiovascular alterations associated with this condition. This study analyzed the development of cardiovascular insulin resistance in a rat model of childhood overweight induced by overfeeding during the lactation period. On birth day, litters were divided into twelve (L12) or three pups per mother (L3). Overfed rats showed a lower increase in myocardial contractility in response to insulin perfusion and a reduced insulin-induced vasodilation, suggesting a state of cardiovascular insulin resistance. Vascular insulin resistance was due to decreased activation of phosphoinositide 3-kinase (PI3K)/Akt pathway, whereas cardiac insulin resistance was associated with mitogen-activated protein kinase (MAPK) hyperactivity. Early overfeeding was also associated with a proinflammatory and pro-oxidant state; endothelial dysfunction; decreased release of nitrites and nitrates; and decreased gene expression of insulin receptor (IR), glucose transporter-4 (GLUT-4), and endothelial nitric oxide synthase (eNOS) in response to insulin. In conclusion, overweight induced by lactational overnutrition in rat pups is associated with cardiovascular insulin resistance that could be related to the cardiovascular alterations associated with this condition.

The aim of this work was to study if early overnutrition in rats is associated with cardiovascular insulin resistance in adulthood. For that purpose we used the experimental model of litter reduction. At birth, rats were organized either in litters of 12 pups/mother (L12-controls) or in litters of 3 pups/mother (L3-Overfed). After weaning rats were fed ad libitum with a standard chow and sacrificed at the age of 6 months. After sacrifice, hearts were set into a Langendorff system whereby increasing insulin doses were administered and coronary perfusion pressure, heart rate and heart contractility were recorded. Likewise, 2mm rings of aorta were mounted in an organ bath whereby changes in vascular tension in response to increasing insulin concentrations were recorded. To assess the activation of the two main pathways involved in insulin intracellular signalling, total proteins were obtained from myocardial and arterial tissues and the MAPK/Akt expression and activation in response to insulin were analyzed. Myocardial contractility in response to insulin was significantly decreased in hearts from overfed rats due to a decreased activation of the PI3K/Akt. On the contrary, in the vascular reactivity experiments insulin induced a higher vasodilation in aorta segments from L3 rats that was not mediated by the activation of the PI3K/Akt pathway and the subsequent release of nitric oxide. In conclusion, overfeeding during lactation in rats induces alterations in vascular function in response to circulating hormones like insulin. This fact could be related with the cardiovascular alterations reported in this experimental mode,

El cadmio es un potente agente tóxico carcinogénico para el ser humano que se utiliza en multitud de procesos industriales. Algunos estudios epidemiológicos han asociado la exposición al cadmio con el cáncer de próstata humano. El trabajo realizado pretende determinar la potencia real del cadmio para inducir tumores, así como estudiar, caracterizar y correlacionar los patrones morfológicos, estereológicos e inmunohistoquímicos de las lesiones inducidas en la próstata ventral de la rata, tras la administración de cloruro de cadmio vía oral. Asimismo, se trata de correlacionar lo antes expuesto con el comportamiento biológico de las lesiones, con el fin de detectar asociación entre los cambios de expresión de diversos marcadores y una mayor agresividad de las lesiones detectadas. De igual manera, se trata de determinar si el zinc en administración conjunta con el cadmio, modifica la incidencia de displasias en la próstata. Los marcadores utilizados para caracterizar las lesiones displásicas son: PCNA, Apoptosis, Ubiquitina, CerbB2, GSTP1,Receptores de Andrógenos, Bcl-2 y TGFß1. También se determinó la densidad numérica de células epiteliales y el contenido de ADN. se concluye que la administración crónica, vía oral, de cloruro de cadmio origina lesiones intraepiteliales en la próstata ventral de la rata, tanto cuando se administra solo como asociado a cloruro de zinc, que se caracterizan por modificaciones en la expresión de diferentes marcadores (aumento de proliferación celular, Bcl-2 y GSTP1, disminución de apoptosis.