Maximal and submaximal treadmill tests in a young adult with fragile-X syndrome.

Fragile X syndrome is associated with expansion of a CGG triplet repeat in the FMR1 gene, which abolishes production of the FMRP protein. This abnormality is expressed as a number of neuro-endocrine disorders (the adrenal axis, macroorchidism) and the emergence of significant behavioural stress. Here, we report on the hormonal status of a young adult with fragile X syndrome, with a focus on catecholamine and cortisol changes during a submaximal treadmill test. The patient showed abnormally high epinephrine and norepinephrine concentrations. During a submaximal incremental test, cortisol levels were higher than the laboratory reference range. Although the submaximal incremental test has a significant "stressful" effect, this young adult was able to complete the entire protocol without any maladaptive behaviour or withdrawal.

Are hormonal responses to exercise in young men with Down's syndrome related to reduced endurance performance?

The aim of the present study was to analyse whether hormonal responses could explain an exercise limitation in Down's syndrome (DS). Fourteen young men with DS (mean age 22.5 +/- 0.7 years) and 15 controls (CONT, mean age 22.5 +/- 0.3 years) participated in the study. During a treadmill submaximal incremental test, blood samples were collected for determination of hormonal and metabolic variables. Compared to CONT, DS individuals showed lower VO(2max) (P < 0.05), and lower duration of submaximal incremental exercise (P < 0.001). At rest, DS individuals showed greater catecholamines, insulin and leptin values (P < 0.05), but lower testosteronemia and cortisolemia (P < 0.05), compared to CONT. During submaximal incremental tests, catecholamines and cortisol were not increased, whereas the insulin concentration of DS individuals was significantly higher (P < 0.01) compared to CONT. Glycaemia increased significantly at the end of submaximal incremental test for CONT but not for DS individuals (P < 0.01). Maximal fat oxidation was lower (P < 0.01), whereas non-esterified fatty acids concentrations rose significantly during submaximal exercise in DS individuals. These results indicate an altered hormonal response to exercise in DS individuals. This endocrine profile at rest and during exercise may limit endurance performance in DS individuals.

Is secondary lymphoid-organ chemokine (SLC/CCL21) much more than a constitutive chemokine?

Chemokines are a superfamily of small cytokines with activities ranging from leukocyte traffick to hematopoiesis, angiogenesis, and tissue organogenesis. Secondary lymphoid-organ chemokine (SLC/CCL21) was originally reported as a chemokine constitutively expressed by stromal cells and high endothelial venules in secondary lymphoid tissues and endothelium of afferent lymphatics, directing CCR7+ cells. More recently, others and we have demonstrated that SLC/CCL21 is up-regulated in different skin inflammatory conditions. Thereafter, this molecule is much more than a constitutive chemokine, which could play a role in effector and regulatory immune functions.

La "entrada y salida" de las células inmunitarias durante la inflamación de la piel: lecciones provenientes de las dermatitis alérgica e irritativa por contacto / The "in and out" of immune cells from the skin during inflammation: lessons from allergic and irritant contact dermatitis

El daño a nivel cutáneo puede tomar diversas formas entre las que se destacan la Dermatitis Alérgica por Contacto (DAC) y la Dermatitis Irritativa por Contacto (DIC). DAC es una enfermedad mediada por linfocitos Th1/ Tc1 y ha sido muy investigada debido a la disponibilidad de un modelo excelente en ratón y la facilidad para reproducir las lesiones en seres humanos. El término DIC es utilizado para describir cambios cutáneos no inmunológicos causados por contacto con sustancias del medio ambiente. En ambas enfermedades, keratinocitos, fibroblastos, células endoteliales y leucocitos infiltrantes interaccionan entre ellos bajo el control de una compleja red de citocinas y mediadores lipídicos. En esta revisión describiremos los mas recientes hallazgos respecto al rol que tienen los vasos sanguíneos y linfáticos en el desarrollo de DAC y DIC (AU)

Expression of CS-1 fibronectin precedes monocyte chemoattractant protein-1 production during elicitation of allergic contact dermatitis.

BACKGROUND: Leucocyte migration within inflammatory skin compartments in allergic contact dermatitis (ACD) is the result of a sophisticated multi-step event where multiple molecules are involved. OBJECTIVE: Since non-antigen-specific mechanisms have been described as an early participant in elicitation of ACD, we investigated the kinetics of the expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) and the type of infiltrating cells. We compared the time course production of MCP-1/CCL2 with connecting segment-1 (CS-1) fibronectin and thymus and activation-regulated chemokine (TARC/ CCL17) expression. METHODS: Biopsies from 10 individuals challenged in their back with the antigen responsible for their contact dermatitis and an irrelevant antigen were taken at different times and histology, immunohistochemistry for CS-1 fibronectin, TARC/CCL17, CD3, CD68, CXCR3, CCR4 and in situ hybridization for MCP-1/CCL2 were performed. RESULTS: At positive antigen stimulated sites expression of MCP-1/CCL2 by basal keratinocytes and isolated cells in dermis started at 10 h. CS-1 fibronectin and TARC/CCL17 expression by blood endothelial cells was found at 2 and 10 h, respectively. This was followed by dermal accumulation of mononuclear cells with a significant increase of CD3+ and CD68+cells. At 48 h, approximately 58% of infiltrating cells were CXCR3+, and 35% CCR4+. CONCLUSIONS: We showed evidence of the fact that CS-1 fibronectin expression precedes the production of MCP-1/CCL2 and TARC/CCL17 in the skin of patients with ACD, suggesting that these molecules participate in the early complex process of migrating mononuclear cells during elicitation of ACD.

[Changes in plasma lipoproteins in adolescents with trisomy 21 in response to a physical endurance test]. / Variations des lipoprotéines plasmatiques chez des adolescents trisomiques 21 en réponse à un test d'endurance physique.

In a previous study, the authors recorded a free fatty acids (FFA) concentration decrease in 11 Down's Syndrome (DS) subjects after an incremental maximal exercise until exhaustion. The aim of this study was to determine if lipid metabolism parameters in a group of DS subjects could be changed after an endurance training period prior to a sustained physical exercise test. After an "adapted" exercise programme, 6 healthy DS subjects, 4 boys and 2 girls aged from 16 to 22 years, performed a sustained exercise lasting 40 minutes on an cycle ergometer. They also compared their values with those taken from the data of laboratory for similarly aged normal subjects. The results of this trial indicate: (a) at rest: (i) a lipid metabolism that included normal level of triglycerides (Trig), but low level of total cholesterol (TC), (ii) a pathological pattern of lipoproteins: low level in high density lipoprotein (HDL), and high level in pré beta very low density lipoprotein (VLDL); (b) after an "adapted" exercise programme period concluding with a final test: (i) an approximate adjustment to normal lipid profiles: rise in HDL and fall in VLDL (ii) a rise of free fatty acids (FFA) between the start and the end of the test. It is noted that physical activity of an endurance type appears to have a favourable long term effect on some manifestations of this genetic disease and that, consequently, such endurance training may be promoted.

Biochemical changes and catecholamine responses in Down's syndrome adolescents in relation to incremental maximal exercise.

The aim of this study was to determine biological responses in Down's syndrome subjects for an incremental exercise lasting 10 min. After a training programme specially adapted for children and adolescents with mental handicaps, 11 healthy Down's syndrome subjects, seven boys and four girls aged from 15 to 20 years, performed a progressive exercise until exhaustion on an ergometric bicycle. The results were compared with those taken from the literature for similar aged normal subjects. The results in our series of Down's syndrome subjects showed: (a) no differences in haematologic parameters, except for a high concentration of uric acid at rest which did not increase after the test; (b) a lower blood lactate level than in maximal exercise for this age range; (c) a late mobilization of FFA; and (d) a slightly lower maximal value of catecholamines. These results may suggest a reduced sympathetic response to maximal exercise.

Physical aptitudes to exertion in children with Down's syndrome.

The individual with Down's syndrome is characterized by apathy towards physical exercise. Ten untrained subjects with Down's syndrome and a control group have been tested at rest and after exercise on a bicycle ergometer. In subjects with Down's syndrome, the authors have observed: (a) a lower orthostatic index at rest; (b) a lower indirect maximal oxygen consumption; (c) a shorter performance time and a lower maximal workload; (d) a higher urinary catecholamines excretion; (e) a blood pressure which did not rise regularly with the workload increment. It is concluded that, in subjects with Down's syndrome, the low level of physical fitness is not only explained by lack of motivation but also by physiological impairments.