Pituitary stalk interruption syndrome: diagnostic delay and sensitivity of the auxological criteria of the growth hormone research society

Objectives

To study the diagnostic delay for pituitary stalk interruption syndrome (PSIS) with growth hormone deficiency (GHD) and the sensitivity of the auxological criteria of the Growth Hormone Research Society (GHRS) consensus guidelines.

Methods

A single-center retrospective case-cohort study covering records from January 2000 through December 2007 evaluated the performance of each GHRS auxological criterion for patients with GHD and PSIS. Diagnostic delay was calculated as the difference between the age at which the earliest GHRS criterion could have been observed and the age at diagnosis of PSIS with GHD. A diagnostic delay exceeding one year was defined as late diagnosis.

Results

The study included 21 patients, 16 (76%) of whom had isolated GHD and 5 (24%) multiple pituitary hormone deficiencies. The median age at diagnosis was 3.6 years (interquartile range, IQR, 2.6–5.5). The median diagnostic delay was 2.3 years (range 0–12.6; IQR 1.5–3.6), with late diagnosis for 17 patients (81%). Height more than 1.5 SDS below target height was the most effective criterion: 90% of the patients met the criterion before diagnosis at a median age of 1 year, and it was the first criterion to be fulfilled for 84%.

Conclusion

In our cohort, the delay for diagnosis of PSIS with GHD was long and could have been reduced by using the GHRS criteria, in particular, height more than 1.5 SDS below the target height. The specificity of such a strategy needs to be tested in healthy populations.     

TRP-2 specifically decreases WM35 cell sensitivity to oxidative stress

TRP-2 (dopachrome tautomerase) is a melanogenic enzyme whose expression was recently reported to modulate melanocyte response to different cytotoxic events. Here we studied a possible role of TRP-2 in the oxidative stress response in the amelanotic WM35 melanoma cell line. Cell viability assays showed that TRP-2 overexpression in WM35 cells reduced their sensitivity to oxidative stress. Comet assays linked TRP-2 expression to DNA damage protection, and high-performance liquid chromotography-tandem mass spectrometry experiments showed an increase in intracellular glutathione in TRP-2-overexpressing cells. These effects were specifically reversed when TRP-2 was silenced by RNA interference. Nevertheless, these properties appeared to depend on a particular cell environment because expression of TRP-2 failed to rescue HEK epithelial cells exposed to similar treatments.     

Steroid metabolism and profile of steroidogenic gene expression in Episkin: high similarity with human epidermis

The skin is a well-recognized site of steroid formation and metabolism. Episkin is a cultured human epidermis. In this report, we investigate whether Episkin possesses a steroidogenic machinery able to metabolize adrenal steroid precursors into active steroids. Episkin was incubated with [14C]-dehydroepiandrosterone (DHEA) and 4-androstenedione (4-dione) and their metabolites were analyzed by liquid chromatography/mass spectrometry (LC/MS/MS). The results show that the major product of DHEA metabolism in Episkin is DHEA sulfate (DHEAS) (88% of the metabolites) while the other metabolites are 7alpha-OH-DHEA (8.2%), 4-dione (1.3%), 5-androstenediol (1.3%), dihydrotestosterone (DHT) (1.4%) and androsterone (ADT) (2.3%). When 4-dione is used as substrate, much higher levels of C19-steroids are produced with ADT representing 77% of the metabolites. These data indicate that 5alpha-reductase, 17beta-hydroxysteroid dehydrogenase (17beta-HSD) and 3alpha-hydroxysteroid dehdyrogenase (3alpha-HSD) activities are present at moderate levels in Episkin, while 3beta-HSD activity is low and represents a rate-limiting step in the conversion of DHEA into C19-steroids. Using realtime PCR, we have measured the level of mRNAs encoding the steroidogenic enzymes in Episkin. A good agreement is found between the mRNAs expression in Episkin and the metabolic profile. High expression levels of steroid sulfotransferase SULT2B1B and type 3 3alpha-HSD (AKR1C2) correspond to the high levels of DHEA sulfate (DHEAS) and ADT formed from DHEA and 4-dione, respectively. 3beta-HSD is almost undetectable while the other enzymes such as type 1 5alpha-reductase, types 2, 4, 5, 7, 8, and 10 17beta-HSD and 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) (AKR1C1) are highly expressed. Except for UGT-glucuronosyl transferase, similar mRNA expression profiles between Episkin and human epidermis are observed.     

Acid-base balance during repeated cycling sprints in boys and men.

The aim of this study was to investigate the acid-base balance during repeated cycling sprints in children and adults. Eleven boys (9.6 +/- 0.7 yr) and ten men (20.4 +/- 0.8 yr) performed ten 10-s sprints on a cycle ergometer separated by 30-s passive recovery intervals. To measure the time course of lactate ([La]), hydrogen ions ([H(+)]), bicarbonate ions ([HCO(3)(-)]), and base excess concentrations and the arterial partial pressure of CO(2), capillary blood samples were collected at rest and after each sprint. Ventilation and CO(2) output were continuously measured. After the 10th sprint, concentrations of boys vs. men were as follows: [La], 8.5 +/- 2.1 vs. 15.4 +/- 2.0 mmol/l; [H(+)], 43.8 +/- 1.3 vs. 66.9 +/- 9.9 nmol/l (P < 0.001). Significant correlations showed that, for a given [La], [H(+)] was lower in the boys compared with the men (P < 0.001). Significant relationships also indicated that, for a given [La], [HCO(3)(-)] and base excess concentration were similar in the boys compared with the men. Moreover, significant relationships revealed that, for a given [H(+)] or [HCO(3)(-)], arterial partial pressure of CO(2) was lower in the boys compared with the men (P < 0.001). The ventilation-to-CO(2) output ratio was higher in the boys during the first five rest intervals and was then higher in the men during the last five sprints. To conclude, during repeated sprints, the ventilatory regulation related to the change in acid-base balance induced by lactic acidosis was more important during the first rest intervals in the boys compared with the men.     

Milk-Derived Antimicrobial Peptides: Overview,Applications, and Future Perspectives

Probiotics and Antimicrobial Proteins - The growing consumer awareness towards healthy and safe food has reformed food processing strategies. Nowadays, food processors are aiming at natural,...