Steroid concentrations in atopic dermatitis patients: Reduced plasma DHEAS and increased cortisone levels.

Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease, which is characterized by a disrupted epidermal barrier function present both in affected skin and in non-affected skin. Mainly glucocorticosteroids were used in topical and systemic atopy treatments because of their potent anti-inflammatory effects, unfortunately with strong side effects. In this study we determined that 2 out of 16 steroids were significantly different in healthy volunteers vs AD-patients. Cortisone, which is higher in AD-patients plasma, is a direct precursor of the bioactive corticosteroid cortisol, which just displays a higher tendency and is known for its potent anti-inflammatory effects. In addition a tendency of reduced levels of the anti-inflammatory ER ligand estrone was found in AD-patients. DHEA is a precursor of testosterone, its levels just display a lower tendency in male AD-patients, while its sulfonation metabolite DHEAS is lower in male and female AD-patients. We found and conclude that altered steroid levels in the plasma of AD-patients indicate altered vitamin D signaling (based on reduced DHEA sulfonation) and increased feedback for anti-inflammatory signaling (increased levels of cortisone) present in AD-patients. This article is protected by copyright. All rights reserved

DJ-1 Null Dopaminergic Neuronal Cells Exhibit Defects in Mitochondrial Function and Structure: Involvement of Mitochondrial Complex I Assembly

DJ-1 is a Parkinson's disease-associated gene whose protein product has a protective role in cellular homeostasis by removing cytosolic reactive oxygen species and maintaining mitochondrial function. However, it is not clear how DJ-1 regulates mitochondrial function and why mitochondrial dysfunction is induced by DJ-1 deficiency. In a previous study we showed that DJ-1 null dopaminergic neuronal cells exhibit defective mitochondrial respiratory chain complex I activity. In the present article we investigated the role of DJ-1 in complex I formation by using blue native-polyacrylamide gel electrophoresis and 2-dimensional gel analysis to assess native complex status. On the basis of these experiments, we concluded that DJ-1 null cells have a defect in the assembly of complex I. Concomitant with abnormal complex I formation, DJ-1 null cells show defective supercomplex formation. It is known that aberrant formation of the supercomplex impairs the flow of electrons through the channels between respiratory chain complexes, resulting in mitochondrial dysfunction. We took two approaches to study these mitochondrial defects. The first approach assessed the structural defect by using both confocal microscopy with MitoTracker staining and electron microscopy. The second approach assessed the functional defect by measuring ATP production, O2 consumption, and mitochondrial membrane potential. Finally, we showed that the assembly defect as well as the structural and functional abnormalities in DJ-1 null cells could be reversed by adenovirus-mediated overexpression of DJ-1, demonstrating the specificity of DJ-1 on these mitochondrial properties. These mitochondrial defects induced by DJ-1mutation may be a pathological mechanism for the degeneration of dopaminergic neurons in Parkinson's disease

Metabolic profiles during an oral glucose tolerance test in pregnant women with and without gestational diabetes.

Background/Aim: Gestational diabetes (GDM) is a complex metabolic condition associated with hyperpglycemia that is diagnosed in an oral glucose tolerance test (OGTT) during pregnancy. For a deeper understanding of the pathology of the disease, further investigations during pregnancy are required, ideally under metabolic challenging conditions. Methods: We performed targeted metabolomics in a group of 24 well-matched women during an oral glucose tolerance test (OGTT). 231 plasma metabolites were profiled and compared to conventional clinical diagnostics. Results: A pattern of 8 metabolites differed between GDM and healthy controls as early as 30min in an OGTT (AUC 0.9770.008), and an increase in acylcarnitine C18:0, decreased concentrations of diacyl phosphatidylcholines (PC aa) C34:4, PC aa C36:4, PC aa C38:5, Lyso PC C20:4 and arachidonic acid were associated with insulin resistance. Conclusion: Our data suggest an additional value of metabolite pattern in the diagnosis of GDM and describe altered pathways that might be subjected to a more precise diagnosis and individualized therapy