Saliva DHEA and cortisol responses following short-term corticosteroid intake.

BACKGROUND: Given the high correlation between the serum and saliva hormone values demonstrated at rest, saliva provides a convenient non-invasive way to determine dehydroepiandrosterone (DHEA) and cortisol concentrations. However, to our knowledge, pituitary adrenal recovery following short-term suppression with corticosteroids has never been investigated in saliva. The aim of this study was therefore to examine how steroid hormone concentrations in saliva are influenced by short-term corticosteroid administration. MATERIALS AND METHODS: We studied saliva DHEA and cortisol concentrations before, during (day 1-day 7) and following (day 8-day 16) the administration of oral therapeutic doses of prednisone (50 mg daily for 1 week) in 11 healthy recreationally trained women. RESULTS: Mean saliva DHEA and cortisol concentrations decreased immediately after the start of prednisone treatment (P < 0.05). Three days after concluding prednisone administration, both saliva DHEA and cortisol had returned to pretreatment levels. CONCLUSIONS: These data are consistent with previous studies on blood samples and suggest that non-invasive saliva samples may offer a practical approach to assessing pituitary-adrenal function continuously during and after short-term corticosteroid therapy.

Salbutamol intake and substrate oxidation during submaximal exercise.

In order to test the hypothesis that salbutamol would change substrate oxidation during submaximal exercise, eight recreationally trained men twice performed 1 h at 60% VO(2) peak after ingestion of placebo or 4 mg of salbutamol. Gas exchange was monitored and blood samples were collected during exercise for GH, ACTH, insulin, and blood glucose and lactate determination. With salbutamol versus placebo, there was no significant difference in total energy expenditure and substrate oxidation, but the substrate oxidation balance was significantly modified after 40 min of exercise. ACTH was significantly decreased with salbutamol during the last 10 min of exercise, whereas no difference was found between the two treatments in the other hormonal and metabolic parameters. The theory that the ergogenic effect of salbutamol results from a change in substrate oxidation has little support during relatively short term endurance exercise, but it is conceivable that longer exercise duration can generate positive findings.

Effects of short-term corticoid ingestion on food intake and adipokines in healthy recreationally trained men.

In order to test the hypothesis that short-term corticoid intake alters food intake, body composition and adipokines secretion in healthy volunteers with regular sport practice, nutrient intake was assessed in eight male athletes with and without prednisolone (PRED, 60 mg/day for 1 week) ingestion in a random, double blind, crossover design. Body weight, body composition, adipokines (i.e., leptin, adiponectin and TNF-alpha), insulin and blood glucose were determined before and at the end of each treatment. PRED did not induce any significant change in body weight, body composition or food intake. Insulin and TNF-alpha were not significantly altered with PRED compared to placebo but blood glucose, leptin and adiponectin concentrations at rest appear significantly increased after PRED treatment (P < 0.05). Our data show that 1 week glucocorticoid treatment does not promote obesity in recreationally trained men but further studies are necessary to understand its effects on the metabolically active hormones, leptin and adiponectin.

Short-term glucocorticoid intake combined with intense training on performance and hormonal responses.

OBJECTIVE: To investigate the effects of short-term prednisolone ingestion combined with intense training on exercise performance, hormonal (adrenocorticotrophic hormone (ACTH), prolactin, luteinising hormone (LH), growth hormone (GH), thyroid-stimulating hormone (TSH), dehydroepiandrosterone (DHEA), testosterone, insulin) and metabolic parameters (blood glucose, lactate, bicarbonate, pH). METHODS: Eight male recreational athletes completed four cycling trials at 70-75% peak O(2) consumption until exhaustion just before (1) and after (2) either oral placebo or prednisolone (60 mg/day for 1 week) treatment coupled with standardised physical training (2 hours/day), according to a double-blind and randomised protocol. Blood samples were collected at rest, during exercise and passive recovery for the hormonal and metabolic determinations. RESULTS: Time of cycling was not significantly changed after placebo but significantly increased (p<0.05) after prednisolone administration (50.4 (6.2) min for placebo 1, 64.0 (9.1) min for placebo 2, 56.1 (9.1) min for prednisolone 1 and 107.0 (20.7) min for prednisolone 2). There was no significant difference in any measured parameters after the week of training with placebo but a decrease in ACTH, DHEA, PRL, GH, TSH and testosterone was seen with prednisolone treatment during the experiment (p<0.05). No significant change in basal, exercise or recovery LH, insulin, lactate, pH or bicarbonate was found between the two treatment, but blood glucose was significantly higher under prednisolone (p<0.05) at all time points. CONCLUSION: Short-term glucocorticoid administration induced a marked improvement in endurance performance. Further studies are needed to determine whether these results obtained in recreational male athletes maintaining a rigorous training schedule are gender-dependent and applicable to elite athletes.

Effects of acute prednisolone administration on exercise endurance and metabolism.

OBJECTIVE: To examine whether acute glucocorticoid (GC) intake alters performance and selected hormonal and metabolic variables during submaximal exercise. METHODS: In total, 14 recreational male athletes completed two cycling trials at 70-75% maximum O(2) uptake starting 3 h after an ingestion of either a lactose placebo or oral GC (20 mg of prednisolone) and continuing until exhaustion, according to a double-blind randomised protocol. Blood samples were collected at rest, after 10, 20, 30 minutes, and at exhaustion and recovery for measurement of growth hormone (GH), adrenocorticotropic hormone (ACTH), dehydroepiandrosterone (DHEA), prolactin, insulin, blood glucose, lactate and interleukin (IL)-6 determination. RESULTS: Cycling duration was not significantly changed after GC or placebo administration (55.9 (5.2) v 48.8 (2.9) minutes, respectively). A decrease in ACTH and DHEA (p<0.01) was observed with GC during all of the experiments and in IL-6 after exhaustion (p<0.05). No change in basal, exercise or recovery GH, prolactin, insulin or lactate was found between the two treatments but blood glucose was significantly higher with GC (p<0.05) at any time point. CONCLUSION: From these data, acute systemic GC administration does seem to alter some metabolic markers but did not influence performance during submaximal exercise.

Short term salbutamol ingestion and supramaximal exercise in healthy women.

OBJECTIVE: To test the hypothesis that chronic salbutamol intake improves performance during supramaximal exercise and to estimate the effects of this treatment on body composition, bone mass, and metabolic indices in healthy women. METHODS: Fourteen female volunteers (seven sedentary and seven recreationally trained) performed a 30 second Wingate test with and without salbutamol ingestion (12 mg/day for four weeks) in a random, double blind, crossover design. Blood samples were collected at rest, at the end of the test, and during passive recovery for lactate measurement. Body composition and bone mass were determined by dual energy x ray absorptiometry. RESULTS: Peak power appeared significantly earlier and was significantly (p<0.05) increased after salbutamol intake in all subjects. There was no difference in total work performed and fatigue indices with salbutamol compared with placebo. No significant alterations in lean or fat body mass and bone variables were observed with salbutamol treatment in either trained or untrained subjects during the trial. In contrast, blood lactate was significantly (p<0.05) increased during the recovery period after salbutamol ingestion compared with placebo. CONCLUSION: As in men, chronic administration of therapeutic concentrations of salbutamol did not induce an anabolic effect in women but increased maximal anaerobic power. Further studies are necessary to clarify the mechanisms involved.

Cardiorespiratory dynamics to hypoxia at the onset of cycling exercise in male endurance subjects.

AIM: It is well established that altering O2 delivering to contracting skeletal muscle affects human performance. In this respect, a reduced O2 supply (e.g., hypoxia) increases the rate of muscle fatigue. This study aimed to determine the effects of moderate hypoxia and exercise intensity on oxygen uptake (VO2) and cardiac output (CO) kinetics during moderate [below the ventilatory threshold (VT)] and heavy (above VT) constant work rate cycling exercises. METHODS: Eight trained males (age, mean+/-SD, 22+/-3 years; height 182+/-5 cm; body mass 71+/-12 kg) performed at the same relative intensity in normoxic (FIO2=0.21) and hypoxic (FIO2=0.13) conditions moderate and heavy exercises during which pulmonary gas exchange was determined breath-by-breath and CO was monitored beat-by-beat with Doppler echocardiography. RESULTS: The rate of increase (t63%, corresponding to time constant and time delay of a monoexponential response) in CO was significantly faster than that of VO2 in 3 out of 4 experimental conditions (p<0.05). Moreover VO2 kinetics were significantly slowed by hypoxia and speeded by exercise intensity, while CO responses were unaffected by such conditions. A slowed CO response was apparent in hypoxia compared to normoxia (p>0.05) in heavy exercise. CONCLUSIONS: These results suggest an absence of coupling between CO and VO2 kinetics, and that cardiorespiratory O2 delivery is likely different at exercise onset as a function of exercise intensity and FIO2.

[Hypopituitarism following traumatic brain injury: diagnostic and therapeutic issues]. / Déficit hypophysaire post-traumatique: enjeux diagnostiques et thérapeutiques.

Traumatic Brain Injury (TBI) is a well-known public health problem worldwide and is a leading cause of death and disability, particularly in young adults. Besides neurological and psychiatric issues, pituitary dysfunction can also occur after TBI, in the acute or chronic phase. The exact prevalence of post-traumatic hypopituitarism is difficult to assess due to the wide heterogeneity of published studies and bias in interpretation of hormonal test results in this specific population. Predictive factors for hypopituitarism have been proposed and are helpful for the screening. The pathophysiology of pituitary dysfunction after TBI is not well understood but the vascular hypothesis is privileged. Activation of pituitary stem/progenitor cells is probably involved in the recovery of pituitary functions. Those cells also play a role in the induction of pituitary tumors, highlighting their crucial place in pituitary conditions. This review updates the current data related to anterior pituitary dysfunction after TBI and discusses the bias and difficulties encountered in its diagnosis.

Concentration of 14 steroid hormones in human amniotic fluid of midpregnancy.

Amniotic fluid (AF) levels of all steroids leading from pregnenolone (delta 5Preg) to androgens and estrogens of both the delta 5 and the delta 4 pathways and those of cortisol and cortisone have been determined in 63 normal pregnancies (12-19 weeks gestation). The 12 unconjugated steroids [delta 5Preg, 17 alpha-hydroxypregnenolone, progesterone, 17 alpha-hydroxyprogesterone, dehydroepiandrosterone (DHA), delta 4-androstenedione, delta 5-androstene-3 beta,17 beta-diol (delta 5Adiol), testosterone (T), estrone, 17 beta-estradiol (E2), cortisol, and cortisone] were measured by specific RIAs after appropriate purification by Celite or LH-20 column chromatography, while the sulfates of DHA and delta 5Preg were assayed directly on diluted samples. There were distinct sex differences; T and delta 4-androstenedione levels were higher (P < 0.001) in males than in females, while AF levels of delta 5Preg, 17 alpha-hydroxypregnenolone, 17-hydroxyprogesterone, DHA, and delta 5Adiol were higher (P < 0.05) in females than in males. AF levels of E2 were significantly higher in females only between 15 and 19 weeks gestation. There was no difference between sexes in AF levels of progesterone, estrone, cortisone, and cortisol. AF levels of T, delta 4-androstenedione, and E2 decreased with age in males, and AF levels of DHA increased in females during the period examined. These observed sex differences suggest that T and delta 4-androstenedione may reflect fetal testicular activity, while E2 and 17-hydroxyprogesterone might reflect fetal ovarian activity. Determination of AF levels of T would appear to be a valuable screening test for antenatal diagnosis of sex (predictive error, less than or equal to 15%), but not in the presence of steroidogenic enzyme defects. Elevated levels of 17-hydroxyprogesterone were found in the AF of two fetuses with either a 17-20 desmolase defect or 21-hydroxylase deficiency; AF levels of androgens were low in the former and high in the latter.

Three-dimensional structure of cyclohexapeptides containing a phosphinic bond in aqueous solution: a template for zinc metalloprotease inhibitors. A NMR and restrained molecular dynamics study.

The 3D structures of two phosphinic cyclic hexapeptide inhibitors of bacterial collagenase, cyclo-(Gly1-Pro2-Phe3 psi[PO2-CH2]Gly4-Pro5-Nle6) (compound I) and cyclo(Gly1-Pro2-D-Phe3 psi[PO2-CH2]-Gly4-Pro5-Nle6) (compound II), in aqueous solution, as derived from NMR spectroscopy and molecular dynamics simulations, are described. The general structures of these cyclic hexapeptides closely resemble the "canonic" two-reverse-turn structure, with the proline occupying the (i + 1) position of the turns and the glycine the connecting positions. The phosphinic bond is located between the (i + 2) and (i + 3) positions of one of these turns. However, a striking feature of the backbone structure of these peptides is the presence of double type VIII-turns in compound I, and in compound II of type VIII- and tentatively named type IX-turns. The comparison of the 3D structures of these two cyclic hexapeptides shows that the stereochemistry of the phenylalanylphosphinyl residue influences not only the local conformation but also the global topology of the peptide macrocycle. The differences in the 3D structure of these compounds are discussed in relation to their inhibitory potencies and with the view of using these constrained cyclic peptides as a scaffold for the development of rigid metalloproteases inhibitors.

Cyclic peptides with a phosphinic bond as potent inhibitors of a zinc bacterial collagenase.

A series of cyclic peptides containing a phosphinic bond were synthesized and evaluated as inhibitors of a zinc bacterial collagenase from Corynebacterium rathaii. Among this series of pseudopeptides of different sizes of cycles, only two molecules Ia (cyclo[Gly-Pro-Phe psi(PO2CH2)-Gly-Pro-Ahx]) and Va (cyclo[beta Ala-Pro-Phe psi (PO2CH2)Gly-Pro-Ahx]) were found to be rather potent inhibitors of this protease, with Ki values of 120 and 90 nM, respectively. Besides the influence of the peptide ring size, this study suggests that both the stereochemical and the conformational properties of the pseudophenylalanine residue in these cyclic peptides may determine their potency. Interestingly, the kinetic analysis for the binding of the cyclic peptide inhibitors Ia and Va to the collagenase, as compared to a linear parent compound, reveals that the lower potency of the cyclic peptides is mostly the consequence of a lower rate constant for association to the enzyme. To our knowledge, this is the first report on cyclic phosphinic peptides and on their activities as inhibitors of a zinc protease.

Controlled comparison of nefazodone and amitriptyline in major depressive inpatients.

Nefazodone, a phenylpiperazine antidepressant, exhibits novel dual activity on serotonin (5-HT) neurons; it binds to 5-HT2 receptors and inhibits 5-HT reuptake. Flexible doses of nefazodone (100-400 mg/day) and amitriptyline (50-200 mg/day) were compared in 106 major depressive inpatients in a 6-week double-blind study. Results showed significant superiority of amitriptyline over nefazodone on all rating instruments: Montgomery and Asberg depression rating scale (P < 0.0001), Hamilton depression scale (P < 0.0006), Clinical Global Impressions (P < 0.0001) and Patient Global Assessment (P < 0.01). A total of 65% of patients under amitriptyline and 56% of patients under nefazodone reported adverse events during the study, with significantly more dry mouth in the amitriptyline group (39% versus 11%, P = 0.001). Modal daily doses within the last treatment week reached 242 mg with nefazodone and 124 mg with amitriptyline. The lower efficacy of nefazodone, which contradicts comparative trials with imipramine in US patients, is discussed with regard to the dose of nefazodone, probably below the optimal therapeutic range for melancholic patients, and to the clinical differences between the patient samples.

Effects of human chorionic gonadotropin, androgens, adrenocorticotropin hormone, dexamethasone and hyperprolactinemia on plasma sex steroid-binding protein.

This presentation reports the effects of androgens, glucocorticoids and some pituitary hormones on plasma sex steroid-binding protein (SBP). The latter was measured by a solid phase method after desteroidation of the plasma. An hCG test (1500 I.U. every other day X 7) was given to 60 boys. In the children with a normal testosterone (T) rise, plasma SBP decreased (% of basal values) either significantly (38.3 +/- 9.3%, group A; n = 29), or moderately (13.4 +/- 4.4%, group B; n = 9) or did not change (-1.6 +/- 6.4%, group C; n = 10). In the 3 infants tested at an age when SBP normally rise sharply, hCG partially prevented this rise. The administration of either fluoxymesterone (10 mg/m2 for 10 days) or depot-T (4 I.M. injections of 100 mg/m2 every 2 weeks) induced a significant drop (about 2-fold) in plasma SBP in a control group of infants or children, but did not change SBP in 3 infants with the androgen insensitivity syndrome. A single injection of 0.25 mg of ACTH did not significantly alter SBP levels. In contrast, at the end of a 3-day ACTH test (0.5 mg/m2 12 hourly X 6) SBP levels had significantly decreased (mean 35% fall) with no age or sex differences, and with no correlation with the cortisol levels reached. However, the lowering effect of ACTH on SBP levels is likely mediated by glucocorticoids, since its effect was reproduced by high doses (8 mg/day for 3 days) of dexamethasone given at once or after 3 days of treatment at lower dose (20 micrograms/kg BW). It would appear that the depressive effect of ACTH and/or dexamethasone is observed for a threshold dose of glucocorticoids (greater than 5-fold physiological levels) and a certain time (greater than or equal to 3 days) of exposure. The mechanism by which androgens and glucocorticoids lower SBP levels in vivo is not yet understood. From recent experiments, showing that both stimulate the secretion of SBP in hepatoma cells in vitro, it would appear that both hormones may alter SBP metabolism. In a selected population of hyperprolactinemic women, with normal weight and no hirsutism, plasma SBP levels were found in the normal female range. The discrepancy with previous studies in the literature may be explained by differences in the degree of hyperprolactinemia and/or associated hyperandrogenim. This study further documents the multifactorial and intricated hormonal influences involved in the regulation of plasma SBP in vivo.

[Study of the reproducibility of cardiac output measurement during exercise in pre-pubertal children by doppler echocardiography and CO2 inhalation]. / Etude de la reproductibilité de la mesure du débit cardiaque à l'exercice chez l'enfant prépubère par échocardiographie doppler et par réinhalation de CO2.

Non-invasive measurement of the cardiac output is essential in investigations of healthy children. However, the data concerning the reproducibility of the measurements are very limited. The aim of this study was to assess the reproducibility of the measurement of cardiac output during exercise by Doppler echocardiography and reinhalation of CO2 (extrapolation method). Fourteen pre-pubertal children underwent two similar tests at increasingly intense levels of exercise. The cardiac output was measured at rest and during the last minute of each stepwise increment of exercise. The results show no difference between the cardiac outputs of the two tests, whichever method was used and at all levels of exercise. They also demonstrate a better reproducibility of cardiac output measurement by Doppler echocardiography (coefficient of variation: 7.5% at rest and 5.2% at maximal effort) compared with reinhalation of CO2 (coefficient of variation: 16.8% at rest and 11.7% at maximal effort). Both methods showed better reproducibility on exercise, resulting from smaller variations in heart rate and stroke volume on effort than at rest. The authors conclude that Doppler echocardiography is very accurate and its simplicity makes it the method of choice in pre-pubertal children for measuring cardiac output during exercise.

Correlation between plasma and saliva adrenocortical hormones in response to submaximal exercise.

This study examined the relationships between plasma and saliva adrenocortical hormones in response to long-duration submaximal exercise. In nine healthy, physically active, female volunteers, blood and saliva samples were taken at rest and every 30 min during a 120-min cycling trial at 50-55% VO(2max) for cortisol and dehydroepiandrosterone (DHEA) analysis. Correlation analysis revealed a moderate but significant relationship between plasma and saliva cortisol (r = 0.35, P < 0.02) and plasma and saliva DHEA (r = 0.47, P < 0.001) during the submaximal exercise. When expressed in percent of resting values, the correlations between the plasma and saliva concentrations were higher for both hormones during the exercise (cortisol: r = 0.72; DHEA: r = 0.68, P < 0.001). The results thus suggest that, even under prolonged exercise conditions, non-invasive saliva samples may offer a practical approach to assessing pituitary-adrenal function, especially when compared with individual basal values.

Effects of acute prednisolone intake on substrate utilization during submaximal exercise.

We examined the hypothesis that acute therapeutic glucocorticoid intake could change the contribution of fat and carbohydrate (CHO) in energy production during exercise. Nine healthy recreationally-trained male subjects twice performed submaximal exercise (60 min at 60 % VO2max) after ingestion of placebo (Pla) or 20 mg of prednisolone (Pred), according to a double blind and randomized protocol. Respiratory exchange was monitored during exercise and blood samples were collected at rest, every 10 min during exercise and after 5, 10, and 20 min of passive recovery. Pred intake significantly increased total energy expenditure during exercise, but CHO oxidation was lower and fat oxidation higher after Pred vs. Pla. ACTH and IL-6 concentrations were significantly decreased with Pred during exercise, whereas no variations were found in GH, insulin, blood glucose, and lactate between the 2 treatments. In conclusion, it appears that acute prednisolone systemic administration does reduce total carbohydrate oxidation during submaximal exercise. Further studies are necessary to clarify the mechanisms involved and to determine whether this modification in the substrate oxidation balance under glucocorticoid administration in recreationally-trained male subjects could result in a competitive advantage in elite athletes.

Effects of acute prednisolone intake during intense submaximal exercise.

To study the effects of a therapeutical dose of corticosteroid alone or associated with beta-2 agonist on performance and substrate response during intense submaximal exercise, seven healthy moderately trained male volunteers participated in the double-blind randomized cross-over study. An intense endurance exercise test to exhaustion was performed after ingestion of placebo (Pla), 20 mg prednisolone (Pred), and 20 mg prednisolone plus 4 mg salbutamol (Pred-Sal). Blood samples were collected at rest, after 5, 10 min of exercise, at exhaustion, and after 5 (r5), 10 (r10), and 20 (r20) min of passive recovery for ACTH, growth hormone, insulin, blood glucose, and lactate measurements. There were no significant differences in exercise time to exhaustion between the three treatments (Pla: 21.5 +/- 2.9; Pred: 22.0 +/- 2.5; Pred-Sal: 24.2 +/- 2.8 min). ACTH was significantly lowered after Pred and Pred-Sal vs. Pla from the start of exercise to the end of the experiment (p < 0.05). Pred and Pred-Sal increased resting and recovery (r10 and r20) significantly but not exercise blood glucose values. There were no significant differences in growth hormone concentrations between the three treatments whereas insulin was significantly higher at rest, during exercise, and at r20 after Pred-Sal administration vs. Pred and Pla (p < 0.05). Pred and Pred-Sal showed no significant effect on blood lactate compared with Pla treatment. These preliminary results do not support the hypothesis that acute oral therapeutic corticosteroid intake alone or associated with beta-2 mimetic improves performance during intense submaximal exercise, but further studies are necessary with tests of longer duration.