Embryonic exposures of lithium and homocysteine and folate protection affect lipid metabolism during mouse cardiogenesis and placentation.

Embryonic exposures can increase the risk of congenital cardiac birth defects and adult disease. The present study identifies the predominant pathways modulated by an acute embryonic mouse exposure during gastrulation to lithium or homocysteine that induces cardiac defects. High dose periconceptional folate supplementation normalized development. Microarray bioinformatic analysis of gene expression demonstrated that primarily lipid metabolism is altered after the acute exposures. The lipid-related modulation demonstrated a gender bias with male embryos showing greater number of lipid-related Gene Ontology biological processes altered than in female embryos. RT-PCR analysis demonstrated significant change of the fatty acid oxidation gene Acadm with homocysteine exposure primarily in male embryos than in female. The perturbations resulting from the exposures resulted in growth-restricted placentas with disorganized cellular lipid droplet distribution indicating lipids have a critical role in cardiac-placental abnormal development. High folate supplementation protected normal heart-placental function, gene expression and lipid localization.

Organizing a dermatology service mission.

BACKGROUND: There are few published guidelines that describe the forethought and logistical considerations needed to create a dermatology-specific medical mission. OBJECTIVE: To report the experience of planning and executing a successful medical mission to an underserved community in Puerto Rico. METHODS: We identified an area of need and projected the volume of patients and diseases to be treated. After recruiting medical staff, pharmaceutical and surgical supplies were collected. Important concerns included establishing the scope of medical and educational services to be rendered, advertising the clinic, arranging for biopsy processing, ensuring follow-up, and selecting a method for medical documentation. We tracked the number of patients seen, diagnoses made, and materials used to prepare for future missions. RESULTS: We recruited 12 physicians and 25 ancillary (i.e. nonlicensed physician) staff members, including: six dermatologists, four internists, one pathologist, one psychiatrist, 23 medical students, and two medical assistants. We secured 12 examination rooms in an existing medical facility. Two pharmaceutical companies and two pathology companies provided the medications and surgical supplies with the remainder coming from the volunteer physicians' offices. Three thousand dollars were raised and used toward purchasing additional supplies. Advertising via public announcements resulted in the attendance of 166 patients during the 1-day clinic. A total of 41 procedures were performed, including 14 biopsies, five excisions, three incisions and drainage, and 19 electrodessications and curettage. CONCLUSION: Proper planning is critical in creating a successful dermatology mission. Documenting the care given and supplies used helps to identify needs and optimize limited resources for future missions. The goal of a self-sustaining public health service starts with patient education and coordination with the local healthcare providers.

Folate rescues lithium-, homocysteine- and Wnt3A-induced vertebrate cardiac anomalies.

Elevated plasma homocysteine (HCy), which results from folate (folic acid, FA) deficiency, and the mood-stabilizing drug lithium (Li) are both linked to the induction of human congenital heart and neural tube defects. We demonstrated previously that acute administration of Li to pregnant mice on embryonic day (E)6.75 induced cardiac valve defects by potentiating Wnt-beta-catenin signaling. We hypothesized that HCy may similarly induce cardiac defects during gastrulation by targeting the Wnt-beta-catenin pathway. Because dietary FA supplementation protects from neural tube defects, we sought to determine whether FA also protects the embryonic heart from Li- or HCy-induced birth defects and whether the protection occurs by impacting Wnt signaling. Maternal elevation of HCy or Li on E6.75 induced defective heart and placental function on E15.5, as identified non-invasively using echocardiography. This functional analysis of HCy-exposed mouse hearts revealed defects in tricuspid and semilunar valves, together with altered myocardial thickness. A smaller embryo and placental size was observed in the treated groups. FA supplementation ameliorates the observed developmental errors in the Li- or HCy-exposed mouse embryos and normalized heart function. Molecular analysis of gene expression within the avian cardiogenic crescent determined that Li, HCy or Wnt3A suppress Wnt-modulated Hex (also known as Hhex) and Islet-1 (also known as Isl1) expression, and that FA protects from the gene misexpression that is induced by all three factors. Furthermore, myoinositol with FA synergistically enhances the protective effect. Although the specific molecular epigenetic control mechanisms remain to be defined, it appears that Li or HCy induction and FA protection of cardiac defects involve intimate control of the canonical Wnt pathway at a crucial time preceding, and during, early heart organogenesis.