Elevated fetal steroidogenic activity in autism.

Autism affects males more than females, giving rise to the idea that the influence of steroid hormones on early fetal brain development may be one important early biological risk factor. Utilizing the Danish Historic Birth Cohort and Danish Psychiatric Central Register, we identified all amniotic fluid samples of males born between 1993 and 1999 who later received ICD-10 (International Classification of Diseases, 10th Revision) diagnoses of autism, Asperger syndrome or PDD-NOS (pervasive developmental disorder not otherwise specified) (n=128) compared with matched typically developing controls. Concentration levels of Δ4 sex steroids (progesterone, 17α-hydroxy-progesterone, androstenedione and testosterone) and cortisol were measured with liquid chromatography tandem mass spectrometry. All hormones were positively associated with each other and principal component analysis confirmed that one generalized latent steroidogenic factor was driving much of the variation in the data. The autism group showed elevations across all hormones on this latent generalized steroidogenic factor (Cohen's d=0.37, P=0.0009) and this elevation was uniform across ICD-10 diagnostic label. These results provide the first direct evidence of elevated fetal steroidogenic activity in autism. Such elevations may be important as epigenetic fetal programming mechanisms and may interact with other important pathophysiological factors in autism.

Citrulline concentration in routinely collected neonatal dried blood spots cannot be used to predict necrotising enterocolitis.

AIM: Low citrulline concentration is a marker of low functional enterocyte mass, which may predispose neonates to necrotising enterocolitis (NEC). We hypothesised that citrulline could be used to assess the NEC risk that could not be accounted for by gestational age and birthweight. This study investigated whether citrulline concentrations routinely measured in neonatal dried blood spots (DBS) could predict NEC. METHODS: We used national Danish registries to retrospectively identify all 361 babies born between 2003 and 2009 who were diagnosed with NEC and had a valid citrulline concentration measured from a DBS sample. The control group comprised 1083 healthy newborns, with three controls for every newborn with NEC, matched for birthweight and gestational age. RESULTS: Neonatal dried blood spots were collected between 2 and 21 days of life, with a median of 8 days. The results showed that NEC was not associated with low citrulline concentration, either in a direct comparison between the NEC and control groups or in a multivariate logistic regression (p = 0.73). CONCLUSION: The findings of this study show that the citrulline concentrations found in routine DBS samples between 2003 and 2009 did not predict NEC in newborn babies.

Retrodialysis: a review of experimental and clinical applications of reverse microdialysis in the skin.

Microdialysis is a method that has been used for decades to recover endogenous mediators, metabolites and drugs from the interstitial space in several tissues of both animals and humans. The principle of microdialysis is the flux of compounds across a semipermeable membrane. The application of microdialysis as a method of drug delivery is a process referred to as retrodialysis, i.e. the introduction of a substance into the extracellular space via a microdialysis probe. Thus, microdialysis also offers opportunities to deliver mediators and drugs to target tissues by adding solutes to the perfusion medium. In this context, retrodialysis combines a method for minimally invasive delivery with a sampling method to study biological processes in health and disease. The aim of this review is to give insight into the use of retrodialysis by outlining examples of retrodialysis studies focusing on applications in skin in animal studies, human experimental investigations and clinical settings.