Recent advances in understanding Cushing disease: resistance to glucocorticoid negative feedback and somatic USP8 mutations

Cushing’s disease is a rare disease with a characteristic phenotype due to significant hypercortisolism driven by over-secretion of adrenocorticotropic hormone and to high morbidity and mortality if untreated. It is caused by a corticotroph adenoma of the pituitary, but the exact mechanisms leading to tumorigenesis are not clear. Recent advances in molecular biology such as the discovery of somatic mutations of the ubiquitin-specific peptidase 8 (USP8) gene allow new insights into the pathogenesis, which could be translated into exciting and much-needed therapeutic applications

Milkfish culture in brackishwater ponds

The manual is intended as a guide for operation in milkfish farming. It is presented under the following major sections: 1) Handling of fry - counting, storage and transport; 2) Pond layout and construction - selection of farm site, layout, construction, plan and specification; 3) Pond operation, culture and management - nursery pond management and rearing pond operation; 4) Harvest and post-harvest - harvest, post harvest, and processing; and 5) Economics and costing - cost of construction, cost of operation, and production/yield

Assessment of glycemic control in nursing home residents with diabetes

International audienceObjective: To describe glycemic control in nursing home residents with diabetes and to evaluate the relevance of HbA1c in the detection of hypoglycemia risk.Design and methods: Diabetes treatment, geriatric assessment, blood capillary glucose (n= 24,682), and HbA1c were collected from medical charts of 236 southern France nursing home residents during a 4-month period. Glycemic control was divided into four categories: tight, fair, and moderate or severe chronic hyperglycemia using the High Blood Glucose Index or the analysis of blood glucose frequency distribution. Hypoglycemia episodes were identified by medical or biological records.Results: Glucose control was tight in 59.3 % and fair in 19.1 % of the residents. Chronic exposure to hyperglycemia was observed in 21.6 % of the residents (severe in 9.7 % and moderate in 11.9 %). Hypoglycemia was noticed in 42/236 (17.8%), in all categories of glycemic control. Relative hypoglycemia risk was significantly (P = 0.0095) higher in residents with moderate chronic hyperglycemia compared with those with tight control. The majority of residents with hypoglycemia (39/42) or chronic hyperglycemia (45/51) were insulin-treated. The relative risk of hypoglycemia was not significantly associated with HbA1c values.Conclusion: Hypoglycemia risk in nursing home residents is observed in all categories of glycemic control. In tight control, the potency of antidiabetic treatment should be reduced. In chronic hyperglycemia, diet and treatment should be reevaluated in order to reduce glucose variability. HbA1c is not sufficient for hypoglycemia risk detection; capillary blood glucose monitoring is warranted for nursing homes residents with diabetes

Pioglitazone in adult rats reverses immediate postnatal overfeeding-induced metabolic, hormonal, and inflammatory alterations

International audienceImmediate postnatal overfeeding in rats, obtained by reducing the litter size, results in early-onset obesity. Such experimental paradigm programs overweight, insulin resistance, dyslipidemia, increased adipose glucocorticoid metabolism [up-regulation of glucocorticoid receptor (GR) and 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1)], and overexpression of proinflammatory cytokines in mesenteric adipose tissue (MAT) in adulthood. We studied the effects of pioglitazone, a PPAR gamma agonist, treatment on the above-mentioned overfeeding-induced alterations. Nine-month-old rats normofed or overfed during the immediate postnatal period were given pioglitazone (3 mg/kg/day) for 6 weeks. Pioglitazone stimulated weight gain and induced a redistribution of adipose tissue toward epididymal location with enhanced plasma adiponectin. Treatment normalized postnatal overfeeding-induced metabolic alterations (increased fasting insulinemia and free fatty acids) and mesenteric overexpression of GR, 11 beta-HSD11, CD 68, and proinflammatory cytokines mRNAs, including plasminogen-activator inhibitor type 1. MesentericGRmRNAlevels correlated positively with mesenteric proinflammatory cytokinesmRNAconcentrations. In vitro incubation of MAT obtained from overfed rats demonstrated that pioglitazone induced a down-regulation of GR gene expression and normalized glucocorticoid-induced stimulation of 11 beta-HSD1 and plasminogen-activator inhibitor type 1 mRNAs. Our data show for the first time that the metabolic, endocrine, and inflammatory alterations induced by early-onset postnatal obesity can be reversed by pioglitazone at the adulthood. They demonstrate that pioglitazone, in addition to its well-established effect on adipose tissue redistribution and adiponectin secretion, reverses programing-induced adipose GR, 11 beta-HSD1, and proinflammatory cytokines overexpression, possibly through a GR-dependent mechanism

Conditions for Existence of Equilibria of Systems With Constant Power Loads

International audienceIn this paper we investigate the sine qua non condition of existence of equilibria for electrical systems with external (AC or DC) sources furnishing constant power to the loads, which is a scenario encountered in modern applications. Two general cases are considered, when the system is i) linear time-invariant or ii) nonlinear, with dynamic behavior described by a port-Hamiltonian model with constant dissipation and switching interconnection matrix. The latter class includes the practically important case of power converters. For both cases necessary and sufficient conditions for existence of equilibria are given, which give an upper bound on the power dissipated in steady-state that should exceed the extracted constant power. The existence of the equilibrium is ensured if and only if the inequality is satisfied