Our aim was to analyze the incidence of mutations in BRCA1 and BRCA2 genes in 54 families with breast/ovarian cancer. Families were selected from three Institutions following the standard criteria for hereditary breast/ovarian cancer. PCR amplification of all exons was performed, followed by SSCP, heteroduplex, PTT and sequencing analysis. We identified eight truncation mutations, three in the BRCA1 gene and five in the BRCA2 gene. Three of these mutations have not been reported previously by other groups: 308insA in one family, 3936 C>T in two families, for BRCA1, and 4970insTG in one family for BRCA2. In addition two families having Ashkenazi Jewish ancestors present the well known mutations 185delAG and 6174delT. Interestingly, 5 out of 11 families have mutations recurrent in Spanish families. Among the 54 families selected, seven have breast and ovary cancer cases, and only two presented a mutation in BRCA1 or BRCA2 genes. Other cancers as prostate and stomach are frequent among relatives carrying the mutation. Five cases of very early onset (<31 years old) breast cancer were detected. The frequencies of BRCA1 (0.074) and BRCA2 (0.13) mutations in our families is low but similar to the incidence found in other populations, like in Spain. Since is widely known that risk factors that modulate the development of breast cancer such as lifestyle risk factors, geographic location, country of origin and socioeconomic status, besides a familial history of breast cancer our findings suggest that the history of colonization and immigrations is very relevant when studying hereditary factors associated to breast cancer.

Acarbose avoided postprandial hypoglycaemia following RYGBP by decreasing the hyperinsulinemic response. This was associated with a decrease in early GLP-1 secretion, in contrast to that observed in non-surgical subjects. This finding could be explained by the reduction of glucose load in the jejunum produced by the α-glucosidase inhibition, which is the main stimulus for GLP-1 secretion.

With about 350 million people chronically infected around the world hepatitis B is a major health problem. Template for progeny HBV synthesis is the viral genome, organized as a minichromosome (cccDNA) inside the hepatocyte nucleus. How viral cccDNA gene expression is regulated by its chromatin structure; more importantly, how the modulation of this structure impacts on viral gene expression remains elusive. Here, we found that the enzyme SetDB1 contributes to setting up a repressed cccDNA chromatin state. This repressive state is activated by the histone lysine demethylase-1 (LSD1). Consistently, inhibiting or reducing LSD1 levels led to repression of viral gene expression. This correlates with the transcriptionally repressive mark H3K9 methylation and reduction on the activating marks H3 acetylation and H3K4 methylation on viral promoters. Investigating the importance of viral proteins we found that LSD1 recruitment to viral promoters was dependent on the viral transactivator protein HBx. Moreover, the histone methyltransferase Set1A and HBx are simultaneously bound to the core promoter, and Set1A expression correlates with cccDNA H3K4 methylation. Our results shed light on the mechanisms of HBV regulation mediated by the cccDNA chromatin structure, offering new therapeutic targets to develop drugs for the treatment of chronically infected HBV patients.

Newborn of altricial species maintain functional gustatory communication with the mother because the neural substrate and the capacity to discriminate and promote gustofacial responses are already operating. Because little is known about the effects of perinatal food restriction upon gustatory neuronal brain stem structures, we characterized neuronal Golgi-Cox alterations of the solitary tract rostral portion (NSTr) where gustatory information is known to convey in neonatal Wistar rats. Pre-and neonatally undernourished rats exhibited a general reduction in the number and extension of distal dendrites particularly in small neurons but little effect upon perikarya measurements of the NSTr neuronal population. By contrast, in nutritional and sensory rehabilitated rats the number of distal dendrites increased, although the dendritic extensions were less affected compared to perinatally underfed and control subjects. The data indicate that perinatal food restriction interferes with the NSTr dendritic arbor organization, while nutritional and sensorial rehabilitation given by normally lactating dams induced plastic changes presumably modifying the integrative processes underlying early taste discriminative capabilities. Moreover, since perinatal food restriction is a powerful stressor influence and the NST forms a part of a complex system underlying adaptive stress responses, the neuronal alterations observed here may be partly due to this noxious perinatal influence.

Weight loss by medical or surgical treatment improved insulin sensitivity. However, only MED corrected the hyperinsulinemic postprandial state associated to obesity. Postprandial GLP-1 levels increased significantly after SG without duodenal exclusion, which may explain why insulin secretion did not decrease following this surgery.