Overtrained horses alter their resting pulsatile growth hormone secretion.

The influence of intensified and reduced training on nocturnal growth hormone (GH) secretion and elimination dynamics was studied in young (1.5 yr) Standardbred geldings to detect potential markers indicative for early overtraining. Ten horses trained on a treadmill for 32 wk in age-, breed-, and gender-matched fixed pairs. Training was divided into four phases (4, 18, 6, and 4 wk, respectively): 1) habituation to high-speed treadmill trotting, 2) normal training, in which speed and duration of training sessions were gradually increased, 3) in this phase, the horses were divided into 2 groups: control (C) and intensified trained (IT) group. In IT, training intensity, duration, and frequency were further increased, whereas in control these remained unaltered, and 4) reduced training (RT). At the end of phases 2, 3, and 4, blood was sampled overnight every 5 min for 8 h for assessment of GH secretory dynamics using pulse detection, deconvolution analysis, and approximate entropy (ApEn). Intensified training induced overtraining (performance decreased by 19% compared with C), which was associated with an increase in concentration peaks number (3.6 vs. 2.0, respectively), a smaller peak secretion pattern with a prolonged half-life (15.2 vs. 7.3 min, respectively), and an increased ApEn (0.89 vs. 0.49, respectively). RT did not lead to full recovery for the overtrained horses. The increased irregularity of nocturnal GH pulsatility pattern is indicative of a loss of coordinated control of GH regulation. Longer phases of somatostatin withdrawal are hypothesized to be the underlying mechanism for the observed changes in GH pulsatility pattern.

Dissociable hormonal, cognitive and mood responses to neuroendocrine challenge: evidence for receptor-specific serotonergic dysregulation in depressed mood.

Fifteen patients with major depression, dysthymia, or anxiety disorder with depressed mood (DSM-IV diagnoses) and 16 controls received single oral doses of 0.5mg/kg metachlorophenylpiperazine (m-CPP), a 5-HT(2C) agonist, and 10 mg ipsapirone, a 5-HT(1A) agonist, according to double-blind, placebo-controlled, cross-over design. The groups' levels of cortisol, adrenocorticotrophic hormone (ACTH) and prolactin did not differ at baseline. Both 5-HT agonists significantly elevated cortisol, ACTH, and prolactin. The cortisol response to ipsapirone was significantly blunted in major depression and dysthymia patients. Neuroendocrine responses to m-CPP did not differ between groups, but m-CPP selectively increased profile of mood states (POMS) depression and tenseness scores in patients. No effects of ipsapirone on mood were found. However, ipsapirone impaired memory performance in controls, but tended to improve memory performance in patients. The results support the evidence for both hypothalamic and possibly hippocampal 5-HT(1A) receptor desensitisation and non-hypothalamic, 5-HT(2C) receptor sensitisation, probably fronto-cortical, in patients with major depression and dysthymia.

Thyroid function, depressed mood, and cognitive performance in older individuals: the Maastricht Aging Study.

The hypothesis was tested that thyroid function, as indicated by serum thyroid-stimulating hormone (TSH) level, is associated with cognitive performance in a healthy aging population. In a random sample of 120 participants recruited from the Maastricht Aging Study (MAAS), aged between 49 and 71 years, we assessed TSH level, mood state (Symptom Check List, subscale depression), and three domains of cognitive function: verbal memory, general sensorimotor speed, and complex flexibility. After correction for age, sex, and educational level, a negative association between TSH and memory function was apparent: higher levels of TSH predicted lower levels of memory performance. Exclusion of individuals with TSH levels suspect for thyroid disorder (n=2) or who were on thyroid replacement (n=3) attenuated this association. Furthermore, additional control for mood status reduced the association below the significance level. No interaction between age and TSH on cognition was found, which indicated that the TSH-memory association was independent of age group level. We conclude that the association between TSH level and memory performance was small and dependent on mood status and the presence of (possible) thyroid disease in this relatively healthy population based sample. Prospective studies are needed to address the role of thyroid function in age-related cognitive decline.

[Successful treatment and pregnancy in a women with the non-classic form of congenital adrenal hyperplasia]. / Succesvolle behandeling en zwangerschap bij een vrouw met de niet-klassieke vorm van het adrenogenitaal syndroom.

In an 18-year-old woman non-classic 21-hydroxylase deficiency was diagnosed and dexamethasone treatment was instituted. Ten years later, she became pregnant for the first time; at 37 weeks unexpected intrauterine foetal death was found to have occurred. A second pregnancy ended with a spontaneous abortion following a 12-week period of amenorrhoea. At the third pregnancy, the medication was replaced with hydrocortisone as it was suspected that the use of dexamethasone may have played a role in the intrauterine foetal death and the spontaneous abortion. The patient gave birth to a healthy, but dysmature, daughter. Female patients with non-classic congenital adrenal hyperplasia present with signs of androgen excess. Treatment with glucocorticoids reduces the symptoms and restores the menstrual cycle and fertility. Preconceptional advice by a clinical geneticist is recommended, because of the risk of an affected child. If there is no risk of having a child with congenital adrenal hyperplasia, hydrocortisone or prednisone is the treatment of choice during pregnancy as neither cross the placenta.

Effect of different head and neck positions on behaviour, heart rate variability and cortisol levels in lunged Royal Dutch Sport horses.

Different head-and-neck positions (HNPs) are discussed in relation to potential welfare issues. To evaluate the effect on welfare, seven Royal Dutch Sport horses were studied in five predetermined HNPs: (1) unrestrained (HNP1); (2) neck raised, bridge of nose around the vertical (HNP2); (3) neck lowered and considerably flexed, bridge of nose pointing towards the chest (HNP4); (4) neck raised and extended, bridge of nose in front of the vertical (HNP5), and (5) neck lowered and flexed, bridge of nose pointing towards the carpus (HNP7). A standardised exercise test (SET) of 34 min consisted of trot, canter and walk. Behaviour was recorded with a pre-defined ethogram and R-R intervals measured using telemetry. Cortisol concentrations were taken at the start, 5 and 30 min after the SET. Behaviour around the SET was scored separately. Conflict behaviours increased significantly during HNP2 when compared with HNP1, HNP4 and HNP7 during the SET, and there was significant negative anticipation before HNP2 and HNP7. The heart rate variability (HRV) frequency domain for HNP2 showed a significantly increased low frequency peak (LFpeak) compared with other HNPs, and there was a decrease in very low frequency (VLF%) compared with HNP1. HNP4 showed a significant increase in LF% and decrease in VLF% compared with HNP1. Saliva cortisol concentrations were significantly increased in HNP2 at 5 and 30 min after exercise. Increased conflict behaviour was mostly observed in HNP2, but there was a raised HRV suggesting a sympathetic shift in HNP2 and HNP4, and increased cortisol concentrations during HNP2 indicated a stress response.

Gonadal function in male and female patients with classic galactosemia.

BACKGROUND: Hypergonadotropic hypoestrogenic infertility is the most burdensome complication for females suffering from classic galactosemia. In contrast, male gonadal function seems less affected. The underlying mechanism is not understood and several pathogenic mechanisms have been proposed. Timing of the lesion, prenatal or chronic post-natal, or a combination of both are not yet clear. METHODS: This review focuses on gonadal function in males and females, ovarian imaging and histology in this disease. It is based on the literature known to the authors and a Pubmed search using the keywords galactosemia, GALT deficiency, (premature) ovarian failure/insufficiency/dysfunction, testicular function, gonadotrophins, FSH, LH (published between January 1971 and April 2009). RESULTS: Male gonads are less affected, boys spontaneously reach puberty, although onset can be delayed. Semen quality has not been extensively studied. Several affected males are known to have fathered a child. Female gonads are invariably affected, although to a varied extent (hypergonadotropic hypoestrogenic ovarian dysfunction). Intriguingly, FSH is often already increased in infancy. Imaging usually shows hypoplastic and streak-like ovaries. Histological findings in some cases reveal the presence of morphologically normal but decreased numbers of primordial follicles, with the absence of intermediate and Graafian follicles. CONCLUSION: Gonads in males seem less affected than in females who exhibit hypergonadotropic hypoestrogenic subfertility. FSH can be elevated in infancy, and ovarian histology sometimes shows the presence of normal primordial follicles with absence of intermediate and Graafian follicles. These findings are similar to other genetic diseases primarily affecting the ovary.

The endocrine system in treated patients with classical galactosemia.

Endocrine abnormalities in classical galactosemia, female hypergonadotropic hypogonadism and low thyroxin in neonates, have been reported. Galactosemia is a secondary glycosylation disorder and hypoglycosylation of glycoproteins has a role in this dysfunction. Hypoglycosylation, improves but does not completely disappear with dietary treatment. Our aim was to evaluate the endocrine system in treated patients (n = 37, 25 females, 12 males, age 5-19 years). Endocrine determinations were compared to age and gender matched reference ranges. Sample t-test (to test differences with reference population) and linear regression analysis between hGH (growth hormone), IGF-1 (insulin-like growth factor), IGFBP-3 (insulin growth factor binding protein), FSH (follicle stimulating hormone), LH (luteinizing hormone) and GALT activity, and soy intake, was carried out. Mean IGF-1 Z-score was -0.98 +/- 0.84 (range -2.59 to 1.21) (P < 0.001) in females and 0.03 +/- 0.55 (range -1.0 to 0.89) (P = 0.84) in males. Mean IGFBP-3 Z-score was -0.98 +/- 1.3 (range -3.0 to 2.0) (P < 0.001) in females and 0.26 +/- 0.93 (range -0.94 to 2.0) (P = 0.35) in males. IGF-1 and IGFBP-3 were positively correlated (P < 0.001). IGF-1 or IGFBP-3 Z-scores and age, hGH, estradiol, GALT activity or soy intake were not correlated. FSH was elevated in females, other axes were normal. Besides the hypergonadotropic hypogonadism in females, IGF-1 and IGFBP-3 are in the low to normal ranges in girls. Hypoglycosylation in galactosemia is diet dependent and could worsen when galactose intake increases either because of poor compliance or diet liberalization.

Prediction of post-traumatic complaints after mild traumatic brain injury: early symptoms and biochemical markers.

OBJECTIVES: To identify parameters at first presentation after mild traumatic brain injury (MTBI) that are predictive of the severity of post-traumatic complaints (PTC) after six months. Early recognition of patients with MTBI who are at risk of developing PTC would be useful because early follow up at the outpatient clinic may help to reduce the severity of these complaints in the long run. METHODS: The presence of symptoms in the emergency room (ER) (headache, dizziness, nausea, vomiting, and neck pain) and biochemical markers (neurone specific enolase and S-100B) in serum were assessed as possible predictive variables for the severity of PTC. Outcome variables were the severity of 16 PTC six months after the trauma. RESULT: After six months, the severity of most complaints had declined to pretrauma levels but medians for headache, dizziness, and drowsiness were still increased. In a series of 79 patients, 22 (28%) reported one or more PTC after six months. After adjustment for baseline variables, an at least twofold increased severity of all PTC subgroups was reported by those patients reporting headache, dizziness, or nausea in the ER. A twofold increased severity of "cognitive" and "vegetative" PTC was also found in those with increased concentrations of biochemical serum markers at first presentation. The prevalence of full recovery after six months increased from 50% in patients with three symptoms to 78% in those with no symptoms in the ER. Inclusion of biochemical markers showed that all 10 patients with no symptoms in the ER and normal markers recovered fully. CONCLUSIONS: The presence of headache, dizziness, or nausea in the ER after MTBI is strongly associated with the severity of most PTC after six months. Identifying MTBI patients in the ER without headache, dizziness, nausea, or increased serum marker concentrations may be a promising strategy for predicting a good outcome.

Olfactory function after mild traumatic brain injury.

OBJECTIVE: The aim of this study was to determine the incidence of olfactory dysfunction after mild traumatic brain injury (MTBI). Damage to the olfactory bulbs or frontal cortex has been reported in MTBI, but olfactory dysfunction after MTBI has not been studied in a prospective way before. DESIGN: Patients with first-time MTBI were included. Patients' olfactory threshold values (Hyposmia Utility Kit by Olfacto-Labs) were measured 2 weeks after the trauma. Associations between olfactory threshold values and individual symptoms and S-100B and NSE concentrations were examined, using multiple linear regression analysis, adjusting for the influence of age. RESULTS: Twenty-two per cent of 111 included patients had hyposmia and 4% had anosmia. Thresholds at 2 weeks showed no significant associations with the presence of symptoms at the ER, nor with early concentrations of S-100B or NSE. CONCLUSIONS: Although a high prevalence of olfactory dysfunction was found, no correlation was found between olfactory dysfunction and acute parameters of MTBI.

Decreased plasma orexin-A levels in obese individuals.

Orexin-A and -B stimulate appetite and food intake in rats. Orexins and orexin receptors are present in the hypothalamus as well as the enteric nervous system, the pancreas and the gut. The presence of orexins in peripheral blood, however, has not yet been reported. To determine whether orexin-A is present in human plasma and is related to body weight, we measured plasma orexin-A and leptin levels in a population with a body mass index (BMI) range from 19.8 to 59 kg/m(2). Plasma orexin-A levels correlated negatively and plasma leptin levels correlated positively with BMI. In obese and morbidly obese individuals, orexin-A levels were significantly lower and leptin levels were significantly higher when compared to normal. Our results support previous data suggesting that orexin-A acts also in a peripheral manner. The fact that lower levels of plasma orexin-A are present in obese individuals suggests that it is involved in the regulation of human energy metabolism.

Determinants of neonatal IgE level: parity, maternal age, birth season and perinatal essential fatty acid status in infants of atopic mothers.

OBJECTIVE: The hygiene hypothesis suggests that the protective 'siblings effect' against atopic diseases such as atopic dermatitis, allergic asthma and hay fever is a result of recurrent infections during early childhood. A recent study and review have indicated that this protective effect may already arise in utero. Lower n-3 essential fatty acid (EFA) status is associated with increased parity, and EFA status has also been related to atopy. The present study confirms the negative association between parity and neonatal immunoglobulin E (IgE) levels and further unravel the role of perinatal EFA status. METHODOLOGY: In a prospective cohort study in 184 atopic mothers and their neonates, we simultaneously measured serum total IgE and EFA levels in plasma phospholipids, both in the mother at 34-36 weeks of gestation and in the neonate at the age of 1 week. Linear regression analysis was used to estimate the effect of parity on maternal and neonatal IgE and EFA status, and the independent effects of parity and EFA status on IgE, controlling for confounding factors such as maternal age and birth season. RESULTS: Parity was associated with lower neonatal IgE level (P < 0.01), as well as with lower docosahexanoic acid (DHA, 22:6n-3) status of the mother (P = 0.01) but not of the neonate (P > 0.69). In the multivariate analysis, higher parity, higher maternal IgE, lower maternal age and birth in the first 3 months of the year were independently associated with neonatal IgE level. No association was detected between maternal or neonatal EFA status and neonatal IgE. CONCLUSIONS: As neonatal total serum IgE is predictive of later atopy, our results support the hypothesis that the sibling effect in atopy is already being programmed in utero. Our data also confirm earlier findings that DHA status is lower in multiparous women, but this did not confound the relation between parity and neonatal IgE.