Increase of interferon-γ inducible α chemokine (C-X-C motif) ligand (CXCL)9 and CXCL11 serum levels in patients with active Graves' disease, and modulation by methimazole therapy.

Background: Chemokine (C-X-C motif) ligand (CXCL)9 and CXCL11 play an important role in the initial phases of autoimmune thyroiditis (AT); however their serum levels in patients with Graves'disease (GD) have never been evaluated in relation to thyroid function and treatment. Methods: To evaluate CXCL9 and CXCL11 serum levels in GD, to relate these parameters to the clinical phenotype, we measured CXCL9 and CXCL11 serum levels in 91 GD patients, 91 AT, 34 non-toxic multinodular goiters (MNG), 31 toxic nodular goiters (TNG) and 91 healthy controls (age- and sex-matched). Results: Mean CXCL9, or CXCL11, levels were higher in GD, in comparison with controls, or euthyroid AT, or MNG, or TNG (*p < 0.05, ANOVA; CXCL9: 274±265, *76±33, *132±78, *87±48, *112±56 pg/mL; CXCL11: 140±92, *64±20, 108±48, *76±33, *91±41 pg/mL; respectively). Hyperthyroid GD had significantly higher CXCL9 or CXCL11 than euthyroid or hypothyroid GD. GD with untreated hyperthyroidism had higher CXCL9 or CXCL11 than hyperthyroid or euthyroid GD under methimazole (MMI) treatment. Comparable CXCL9 and CXCL11 levels were observed in newly diagnosed untreated hyperthyroid GD vs. untreated patients with relapse of hyperthyroidism after a previous MMI course. Conclusions: Serum CXCL9, and CXCL11, levels are associated with the active phase of GD both in newly diagnosed and relapsing hyperthyroid patients. The reduction of serum CXCL9 and CXCL11 levels in treated patients with GD may be related to the immunomodulatory effects of MMI

Effect of a fatty meal on inflammatory markers in healthy volunteers with a family history of type 2 diabetes

A family history of type 2 diabetes (T2D) confers a high risk of developing the disease, independent of that due to other common risk factors. Postprandial state is a pro-inflammatory condition associated with a transiently impaired endothelial function; an increased oxidative stress is considered as a mediator of such effects in T2D. We evaluated the short-term effect of a lipid meal on markers of early vascular damage in subjects at risk of developing T2D. A total of thirty-two healthy volunteers, divided according to the presence (FHD+) or absence (FHD - ) of a family history of T2D, underwent a fatty meal test. We measured the monocyte mRNA expressions of IL-6, IL-8 and IL-1β, and IL-6, soluble CD40 ligand (sCD40L), vascular cellular adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1) and nitrotyrosine plasma concentrations at baseline and in the post-meal phase, relating them to the lipid profile and other biochemical parameters. The basal expression of the cytokines did not differ in FHD - and FHD+ subjects; neither was it modified by the meal ingestion. IL-6 and sCD40L plasma levels, similar in the two groups in the fasting state, did not vary after the meal. VCAM-1 and ICAM-1 increased in FHD+ subjects but not in FHD - subjects. Nitrotyrosine, similar between the FHD - and FHD+ subjects at baseline, increased more in FHD+ subjects than in FHD - subjects after the meal. In conclusion, the presence of a familial history of T2D confers an abnormal endothelial activation after an oral lipid meal, coupled with an increased oxidative stress, supporting the hypothesis of an early endothelial dysfunction already present in healthy individuals prone to develop T2D

Extra-ocular muscle cells from patients with Graves' ophthalmopathy secrete α (CXCL10) and β (CCL2) chemokines under the influence of cytokines that are modulated by PPARγ

To our knowledge, no study has evaluated the involvement of T helper (Th)1- and Th2-chemokines in extra-ocular muscle (EOM) myopathy in "patients with thyroid-associated ophthalmopathy" (TAO-p). We tested the effects of interferon (IFN)γ and tumor necrosis factor (TNF)α stimulation, and of increasing concentrations of peroxisome proliferator-activated receptor (PPAR)γ agonists (pioglitazone or rosiglitazone; 0.1μM-20μM), on Th1-chemokine [C-X-C motif ligand (CXCL)10] and Th2-chemokine [C-C motif ligand (CCL)2] secretion in primary EOM cultures from TAO-p vs. control myoblasts. Moreover, we evaluated serum CXCL10 and CCL2 in active TAO-p with prevalent EOM involvement (EOM-p) vs. those with prevalent orbital fat expansion (OF-p). Serum CXCL10 was higher in OF-p and EOM-p vs. controls, while serum CCL2 was not significantly different in controls, or in OF-p and EOM-p. We showed the expression of PPARγ in EOM cells. In primary EOM cultures from TAO-p: a) CXCL10 was undetectable in the supernatant, IFNγ dose-dependently induced it, whereas TNFα did not; b) EOM produced basally low amounts of CCL2, TNFα dose-dependently induced it, whereas IFNγ did not; c) the combination of TNFα and IFNγ had a significant synergistic effect on CXCL10 and CCL2 secretion; and d) PPARγ agonists have an inhibitory role on the modulation of CXCL10, while they stimulate CCL2 secretion. EOM participates in the self-perpetuation of inflammation by releasing both Th1 (CXCL10) and Th2 (CCL2) chemokines under the influence of cytokines, in TAO. PPARγ agonist activation plays an inhibitory role on CXCL10, but stimulates the release of CCL2

Long-term effects of bariatric surgery on meal disposal and beta-cell function in diabetic and nondiabetic patients.

Gastric bypass surgery leads to marked improvements in glucose tolerance and insulin sensitivity in obese type 2 diabetes; the impact on glucose fluxes in response to a physiological stimulus - such as a mixed meal (MTT) - has not been determined. We administered an MTT to 12 obese type 2 diabetic patients (T2D) and 15 obese nondiabetic subjects (ND) before and one year after surgery (10 T2D and 11 ND) using the double-tracer technique and modeling of ß-cell function. In both groups postsurgery, tracer-derived appearance of oral glucose was biphasic, a rapid increase followed by a sharp drop, a pattern that was mirrored by postprandial glucose levels and insulin secretion. In diabetic patients, surgery lowered fasting and postprandial glucose levels; peripheral insulin sensitivity increased in proportion to weight loss (∼30%), ß-cell glucose sensitivity doubled but did not normalize (viz. 21 nonsurgical obese and lean controls). Endogenous glucose production, however, was less suppressed during the MMT as the combined result of a relative hyperglucagonemia and the rapid fall in plasma glucose and insulin levels.We conclude that, in type 2 diabetes bypass surgery changes the postprandial response to a dumping-like pattern, improves glucose tolerance, ß-cell function, and peripheral insulin sensitivity but worsens endogenous glucose output in response to a physiological stimulus

Fiesta y trabajo: la oposición entre conquistadores y conquistados. Parte II

Segunda parte del trabajo en el que se aborda la relación fiesta-trabajo en la cultura rarámuri como oposición a la cultura occidental. En este bloque se habla del trabajo como la religión del hombre blanco, considerada actividad fundamental para la subsistencia e instrumento único para la humanización de la sociedad. Desde esta perspectiva, el trabajo es planteado como camino único hacia la liberación de la necesidad traducida generalmente en términos de fiesta o supresión del trabajo. Se habla de los resultados y consecuencias del proyecto occidental del trabajo en comparación con la concepción de esta actividad en otros grupos humanos

Physiology of glucose homeostasis and insulin therapy in type 1 and type 2 diabetes.

An input-output schematization of plasma glucose homeostasis provides quantitative information on glucose fluxes and their control by insulin. Insulin action is dependent on the target tissue, the route of delivery, and the kinetics of insulin activation and deactivation, which are different for glucose production and disposal and are a function of insulin resistance. Under normal conditions, the closed-loop control of minute-by-minute insulin release by arterial glucose levels protects against both hyperglycemia and hypoglycemia. Open-loop insulin therapy faces the complexities of insulin pharmacokinetics and pharmacodynamics. Insulin therapy thus remains defiantly empiric