Maternal obesogenic diet induces endometrial hyperplasia, an early hallmark of endometrial cancer, in a diethylstilbestrol mouse model.

Thirty-eight percent of US adult women are obese, meaning that more children are now born of overweight and obese mothers, leading to an increase in predisposition to several adult onset diseases. To explore this phenomenon, we developed a maternal obesity animal model by feeding mice a diet composed of high fat/ high sugar (HF/HS) and assessed both maternal diet and offspring diet on the development of endometrial cancer (ECa). We show that maternal diet by itself did not lead to ECa initiation in wildtype offspring of the C57Bl/6J mouse strain. While offspring fed a HF/HS post-weaning diet resulted in poor metabolic health and decreased uterine weight (regardless of maternal diet), it did not lead to ECa. We also investigated the effects of the maternal obesogenic diet on ECa development in a Diethylstilbestrol (DES) carcinogenesis mouse model. All mice injected with DES had reproductive tract lesions including decreased number of glands, condensed and hyalinized endometrial stroma, and fibrosis and increased collagen deposition that in some mice extended into the myometrium resulting in extensive disruption and loss of the inner and outer muscular layers. Fifty percent of DES mice that were exposed to maternal HF/HS diet developed several features indicative of the initial stages of carcinogenesis including focal glandular and atypical endometrial hyperplasia versus 0% of their Chow counterparts. There was an increase in phospho-Akt expression in DES mice exposed to maternal HF/HS diet, a regulator of persistent proliferation in the endometrium, and no difference in total Akt, phospho-PTEN and total PTEN expression. In summary, maternal HF/HS diet exposure induces endometrial hyperplasia and other precancerous phenotypes in mice treated with DES. This study suggests that maternal obesity alone is not sufficient for the development of ECa, but has an additive effect in the presence of a secondary insult such as DES

Phylogenetic and functional analysis of ADAMTS13 identifies highly conserved domains essential for allosteric regulation

The metalloprotease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats member 13) prevents microvascular thrombosis by cleaving von Willebrand factor (VWF) within platelet-rich thrombi, and cleavage depends on allosteric activation of ADAMTS13 by the substrate VWF. Human ADAMTS13 has a short propeptide, metalloprotease (M), disintegrin-like (D), thrombospondin-1 (T), Cys-rich (C), and spacer (S) domains (proximal domains), followed by 7 T and 2 CUB (complement components C1r and C1s, sea urchin protein Uegf, and bone morphogenetic protein-1) domains (distal domains). Distal domains inhibit the catalytic proximal domains; binding of distal T8-CUB domains to the VWF D4 domain relieves autoinhibition and promotes cleavage of the nearby VWF A2 domain. However, the role of specific ADAMTS13 distal domains in this allosteric mechanism is not established. Assays of plasma ADAMTS13 from 20 placental mammals, birds, and amphibians show that allosteric regulation is broadly conserved, and phylogenetic analysis of 264 vertebrates shows the long propeptide, T3, T4, T6, and T6a domains have been deleted several times in placental mammals, birds, and fish. Notably, pigeon ADAMTS13 has only 3 distal T domains but was activated normally by human VWF D4 and cleaved VWF multimers, preferentially under fluid shear stress. Human ADAMTS13 constructed to resemble pigeon ADAMTS13 retained normal allosteric regulation and shear-dependent cleavage of VWF. Thus, the T3-T6 domains of human ADAMTS13 are dispensable. Conversely, deletion of T7 or T8 abolished allosteric activation. For most species, some sequence changes in the VWF substrate can markedly increase the rate of cleavage, suggesting that ADAMTS13 and VWF have not evolved to be optimal enzyme-substrate pairs. These properties may reflect evolutionary pressure to balance the risk for VWF-dependent bleeding and thrombosis.status: publishe

Educação em saúde com trabalhadores: relato de uma experiência

Workers generally need to have, in their place of work, some moments in which they can talk and know other ones’ opinions about their helth-disease process. Enterprises that invest in this moment have a gain in their workers’ motivation, involvement and responsability, what directly reflects in their productiveness. Based on this, and from a request to us to gauge the blood pressure of workers from a car selling and maintenance enterprise, from March to September of the year 2006, we began a health educational work in this enterprise. This work is a report of the experience with these workers, with the purpose to contribute to the prevention of diseases and stimulate the promotion of workers’ health. Therefore, through a work group with five students from the seventh grade of the graduation course of the Faculdade de Enfermagem of the Universidade Federal de Juiz de Fora (FACEN/UFJF) with the supervision of a professor who is specialist in worker health subject, we managed to develop a significative experience that we believe to have contributed in an effective way in the development of a distinct attention to the worker, emphasizing and stimulating the practice of a healthy and productive work life.Os trabalhadores, de modo geral, necessitam, em seu local de trabalho, de momentos em que possam falar e trocar idéias sobre o seu processo saúde-doença. As empresas que investem neste momento ganham na motivação, no envolvimento, no compromisso de seus trabalhadores, o que irá refletir diretamente na produtividade. Baseados nisso, e a partir de um convite para irmos aferir a pressão arterial dos trabalhadores de uma empresa responsável pela venda e manutenção de automóveis, de março a setembro de 2006, iniciamos um trabalho de educação em saúde nesta empresa. Este trabalho é um relato dessa experiência com estes trabalhadores, com o objetivo de contribuir para a prevenção de doenças e estimular a promoção da saúde dos trabalhadores. Assim, através de uma equipe de trabalho composta por cinco alunas do sétimo período do curso de graduação da Faculdade de Enfermagem da Universidade Federal de Juiz de Fora (FACENF/UFJF) sob a supervisão de uma docente especialista na área de saúde do trabalhador, foi possível desenvolver uma experiência significativa que acreditamos ter contribuído de maneira efetiva na construção de uma atenção diferenciada para o trabalhador, enfatizando e estimulando o exercício de uma vida laboral saudável e produtiva

Maternal diet induces changes in phospho-Pten and phospho- Akt protein expression in DES treated mice.

<p>Immunoblot images and quantification of phospho-Pten and total Pten (<b>A</b>), phospho-Akt and total Akt (<b>B</b>), and immunoblot of Estrogen receptor α (<b>C</b>).</p

Serum hormone levels in 72 week-old F1 offspring.

<p>Estradiol (<b>A</b>), Estrone (<b>B</b>), FSH (<b>C</b>) and LH (<b>D</b>). N > 5 mice per cohort, *p<0.05, 2-way ANOVA followed by Tukey’s multiple comparison test. Same letters mean there is no significant difference between conditions, different letters represent statistically significant differences at p<0.01.</p

Histological report of 24 week old mice exposed to either maternal Chow or HF/HS diet and injected with vehicle control (VEH) or DES.

<p>Histological report of 24 week old mice exposed to either maternal Chow or HF/HS diet and injected with vehicle control (VEH) or DES.</p