Immune function in Trachemys scripta following exposure to a predominant brevetoxin congener,PbTx-3, as a model for potential health impacts for sea turtles naturally exposed to brevetoxins

Ecotoxicology - Many species of marine life in southwestern Florida, including sea turtles, are impacted by blooms of the toxic dinoflagellate, Karenia brevis. Sublethal exposure to toxins produced...     

The effect of gonadal and adrenal steroid therapy on skeletal health in adolescents and young women with anorexia nervosa

Anorexia nervosa (AN) is characterized by subnormal estrogen and dehydroepiandrosterone (DHEA) levels. We sought to determine whether the combination of DHEA + estrogen/progestin is superior to placebo in preserving skeletal health over 18 months in AN. Females with AN, aged 13 to 27 years, were recruited for participation in this double-blind, placebo-controlled, randomized trial. Ninety-four subjects were randomized, of whom 80 completed baseline assessments and received either study drug (oral micronized DHEA 50 mg + 20 μg ethinyl estradiol/0.1 mg levonorgestrel combined oral contraceptive pill [COC] daily; n = 43) or placebo (n = 37). Serial measurements of areal bone mineral density (aBMD), bone turnover markers, and serum hormone concentrations were obtained. Sixty subjects completed the 18-month trial. Spinal and whole-body aBMD z scores were preserved in the DHEA + COC group, but decreased in the placebo group (comparing trends, P = .008 and P = .001, respectively). Bone turnover markers initially declined in subjects receiving DHEA + COC and then returned to baseline. No differences in body composition, adverse effects of therapy, or alterations in biochemical safety parameters were observed. Combined therapy with DHEA + COC appears to be safe and effective for preventing bone loss in young women with AN, whereas placebo led to decreases in aBMD. Dehydroepiandrosterone + COC may be safely used to preserve bone mass as efforts to reverse the nutritional, psychological, and other hormonal components of AN are implemented.     

Pancreatic Islet Vasculature Adapts to Insulin Resistance Through Dilation and Not Angiogenesis

Pancreatic islets adapt to insulin resistance through a complex set of changes, including β-cell hyperplasia and hypertrophy. To determine if islet vascularization changes in response to insulin resistance, we investigated three independent models of insulin resistance: ob/ob, GLUT4^+/−, and mice with high-fat diet–induced obesity. Intravital blood vessel labeling and immunocytochemistry revealed a vascular plasticity in which islet vessel area was significantly increased, but intraislet vessel density was decreased as the result of insulin resistance. These vascular changes were independent of islet size and were only observed within the β-cell core but not in the islet periphery. Intraislet endothelial cell fenestration, proliferation, and islet angiogenic factor/receptor expression were unchanged in insulin-resistant compared with control mice, indicating that islet capillary expansion is mediated by dilation of preexisting vessels and not by angiogenesis. We propose that the islet capillary dilation is modulated by endothelial nitric oxide synthase via complementary signals derived from β-cells, parasympathetic nerves, and increased islet blood flow. These compensatory changes in islet vascularization may influence whether β-cells can adequately respond to insulin resistance and prevent the development of diabetes.Pancreatic islets are highly vascularized, and this feature is critical for β-cells to rapidly sense the blood glucose and secrete insulin into the systemic circulation (1,2). Islet vascularization begins early in pancreas development and is maintained in adulthood as a consequence of islet cell production of angiogenic factors such as vascular endothelial growth factor-A (VEGF-A) and angiopoietin-1 (Ang-1) (3–6). These factors recruit endothelial cells (ECs), stimulate blood vessel growth and maturation, and in the case of VEGF-A, promote formation of EC fenestrations (5,6). In addition, ECs adjacent to pancreatic epithelium reciprocally influence islet cell differentiation and development (7,8).β-Cells have a remarkable ability to respond to changes in an organism’s metabolic state, such as changes in the blood glucose or increased insulin requirements. For example, when insulin resistance develops, β-cells of the pancreatic islet can dramatically increase insulin production and secretion with an increase of β-cell mass, thus maintaining normoglycemia (9,10). In this way, mouse models with marked insulin resistance and humans with obesity-related insulin resistance are hyperinsulinemic but not hyperglycemic. The mechanisms underlying this β-cell adaptation to insulin resistance and their subsequent failure in some individuals who develop type 2 diabetes are incompletely understood.Because of the highly vascularized state of pancreatic islets and the marked changes in β-cell size and number in the setting of insulin resistance, we hypothesized that the islet vasculature must adapt to these changes in β-cell mass and insulin requirements. We envisioned that a hyperplastic islet, like a growing tumor mass, would increase production of angiogenic factors to increase its vascular supply with expanding β-cell mass (11). To test this hypothesis, we examined islet vascularization in three mouse models of insulin resistance and found, unexpectedly, that islet vessel density was decreased, not increased, and that the intraislet vasculature became markedly dilated whereas vessels in the exocrine tissue were unchanged. The dilation of intraislet capillaries was independent of islet size, suggesting the vascular adaptation may primarily support increased β-cell insulin secretory demand rather than β-cell mass expansion. Moreover, these vascular changes were accompanied by an increase in islet parasympathetic innervation. Our results indicate that the metabolic state influences islet angioarchitecture and innervation, suggesting that islet neurovascular remodeling may influence whether β-cells can adequately respond to insulin resistance and maintain normoglycemia.