„Steroidprofile“: diagnostische Fingerabdrücke endokriner Erkrankungen. Das neue Steroidlabor am Zentrum für Kinderheilkunde und Jugendmedizin

Im Januar 2001 hat in der Abteilung Allgemeine Pädiatrie und Neonatologie (Leiter: Prof. Dr. Ludwig Gortner) am Zentrum für Kinderheilkunde und Jugendmedizin ein neu etabliertes Labor seine Tätigkeit aufgenommen. Sein Profil bietet für die Bereiche Forschung und Entwicklung, aber auch als klinische Serviceeinrichtung eine bundesweit einzigartige endokrinologische Analytik an, nämlich die Identifizierung und Quantifizierung von Steroiden oder Steroidhormonen mittels Gaschromatographie-Massenspektrometrie

Fault Detection and Classification in Transmission Line Using Wavelet Transform and ANN

In recent years, there is an increased interest in fault classification algorithms. The reason, behind this interest is the escalating power demand and multiple interconnections of utilities in grid. This paper presents an application of wavelet transforms to detect the faults and further to perform classification by supervised learning paradigm. Different architectures of ANN are tested with the statistical attributes of a wavelet transform of a voltage signal as input features and binary digits as outputs. The proposed supervised learning module is tested on a transmission network. It is observed the Layer Recurrent Neural Network (LRNN) architecture performs satisfactorily when it is compared with the simulation results. The transmission network is simulated on Matlab. The performance indices Mean Square Error (MSE), Mean Absolute Error (MAE), Root Mean Square Error (RMSE) and Sum Square Error (SSE) are used to determine the efficacy of the neural network

Higher steroid sulfation is linked to successful weight loss in obese children

Objective: Little information is available on the steroid sulfates profile in obese children. Therefore, we examined whether sulfated steroids are linked with weight status and associated comorbidities in obese children. Methods: We analyzed 66 obese children (mean age 10.5 ± 2.5 years, 57.6% female, 53.9% prepubertal, mean BMI 27.0 ± 4.6 kg/m2, 50% with BMI-SDS reduction >0.5, 50% without BMI-SDS reduction) who participated in an outpatient 1-year intervention program based on exercise, behavior and nutrition therapy. We measured intact sulfated steroids (cholesterol sulfate (CS), pregnenolone sulfate (PregS), 17αOH pregnenolone sulfate (17OH-PregS), 16αOH dehydroepiandrosterone sulfate (16OH-DHEAS), DHEAS, androstenediol-3-sulfate, androsterone sulfate and epiandrosterone sulfate) by LC–MS/MS, and insulin resistance index HOMA, lipids, blood pressure at baseline and 1 year later. Results: All sulfated steroids except 17OH-PregS, 16OH-DHEAS, androsterone sulfate and epiandrosterone sulfate were higher in boys compared to girls. Concentrations of CS before intervention were higher in children who lost weight. After 1 year of treatment, both groups showed increased levels of DHEAS, 16OH-DHEAS and androstenediol-3-sulfate, but PregS was only increased in children with weight loss. None of the steroid sulfates was significantly related to cardiovascular risk factors or HOMA except 17OH-PregS, which was associated with systolic blood pressure both in cross-sectional (β-coefficient: 0.09 ± 0.07, P = 0.020) and longitudinal analyses (β-coefficient: 0.06 ± 0.04, P = 0.013) in multiple linear regression analyses. Conclusions: Since higher steroid sulfation capacity was associated with successful weight intervention in children disruption of sulfation may be associated with difficulties to lose weight. Future studies are necessary to prove this hypothesis

Virilization of a Young Girl Caused by Concomitant Ectopic and Intra-Adrenal Adenomas of the Adrenal Cortex

Background: Adenomas of the adrenal gland are rare causes ofvirilization in childhood. Case Report: A girl aged 2 years and 4 monthspresented with pubarche, distinct clitoral hypertrophy, tall stature,and increased height velocity. Plasma testosterone anddehydroepiandrosterone were elevated. Androgens remained unchanged afteradrenocorticotropic hormone, and dexamethasone administrations.Ultrasound examination and magnetic resonance imaging indicated anextra-adrenal mass adjacent to the left adrenal gland, which was removedby endoscopic surgery. However, plasma androgens remained elevated and131 I-iodomethyl-norcholesterol scintigraphy revealed tracer enhancementin the right adrenal gland, which was consecutively removed.Virilization regressed after extirpation of the adenomas and heightvelocity normalized. Results: Histology revealed a circumscribed adenomain the right adrenal gland and an epithelial mass with adrenal corticalcells in the left-sided ectopic tumor. In the ectopic tumor,melanocortin 2 receptor expression was augmented threefold compared tothe control, indicating adrenal origin. Conclusions: In this young girl,virilization is due to concomitant ectopic and intra-adrenal adenomas ofthe adrenal cortex. By melanocortin 2 receptor expression, it wasconfirmed that the ectopic adenoma derived from the adrenal cortex.Specific scintigraphy, if available, assists in allocating the source ofandrogen hypersecretion

Differentiation of heroin and cocaine using dual-energy CT—an experimental study

Objective: To evaluate if heroin and cocaine can be distinguished using dual-energy CT. Materials and methods: Twenty samples of heroin and cocaine at different concentrations and standardized compression (SC) were scanned in dual-energy mode on a newest generation Dual Energy 64-row MDCT scanner. CT number, spectral graphs, and dual-energy index (DEI) were evaluated. Results were prospectively tested on six original samples from a body packer. Wilcoxon's test was used for statistical evaluation. Results: Values are given as median and range. Under SC, the CT number of cocaine samples (−29.87 Hounsfield unit (HU) [−125.85; 16.16HU]) was higher than the CT number of heroin samples (−184.37HU [−199.81; −159.25HU]; p < 0.01). Slope of spectral curves for cocaine was −2.36HU/keV [−7.15; −0.67HU/keV], and for heroin, 1.75HU/keV [1.28; 2.5HU/keV] (p < 0.01). DEI was 0.0352 [0.0081; 0.0528] for cocaine and significantly higher than for heroin samples (−0.0127 [−0.0097; −0.0159]; p < 0.001). While CT number was inconclusive, all six original packs were correctly classified after evaluation of the spectral curve and DEI. In contrast to the CT number, slope of the spectral curve and DEI were independent of concentration and compression. Conclusion: The slope of the spectral curve and the DEI from dual-energy CT data can be used to distinguish heroin and cocaine in vitro; these results are independent of compression and concentration in the measured range

Laser beam shape optimization: Exploring alternative profiles to Gaussian-shaped laser beams in powder bed fusion of metals

Laser-based powder bed fusion of metals (PBF-LB/M) commonly utilizes Gaussian-shaped laser beams characterized by a high intensity at the center. However, this type of profile leads to localized high temperatures and temperature gradients. When the laser power is increased beyond a certain threshold, the temperature inside the melt pool can reach the boiling point, causing excessive metal evaporation, hydrodynamic instabilities, and undesired effects such as keyholing. On the other hand, ring-shaped laser beams generate a more uniform temperature distribution but tend to produce shallower, wider, and shorter melt pools with reduced resolution compared to the Gaussian profiles. The deep, narrow, and elongated melt pools generated by the Gaussian shapes still have advantages for increased precision in the PBF-LB/M processes. This contribution uses numerical optimization to generate a new laser beam shape that also leads to a deep, narrow, and elongated melt pool, similar to a Gaussian-shaped beam, while maintaining a lower and more uniform temperature distribution inside the melt pool. The resulting optimized laser profile lowers the maximum laser intensity by 40 % without decreasing the total laser power compared to the Gaussian profile. The more uniform distribution of temperature with a peak value of just above 3 000 ◦C indicates a conduction dominated process with less hydrodynamic and minimal evaporative effects. This is expected to reduce the associated defects and improve the process stabilityMechanical Engineerin

Sunitinib Inhibits Cell Proliferation and Alters Steroidogenesis by Down-Regulation of HSD3B2 in Adrenocortical Carcinoma Cells

The multi-tyrosine kinase inhibitor sunitinib is used in the treatment of several solid tumors. Animal experiments pointed to an adrenotoxic effect of sunitinib. Therefore, we evaluated the expression of key targets of sunitinib in human adrenocortical carcinoma (ACC) tumor samples and investigated its in vitro effects in ACC cell lines. We carried out immunohistochemistry for vascular endothelial growth factor (VEGF) and its receptor (VEGF-R2) in 157 ACC samples and nine normal adrenal glands. VEGF and VEGF-R2 protein were expressed in 72 and 99% of ACC samples, respectively. Using NCI-H295 and SW13 ACC cell lines, we investigated the effects of sunitinib on cell proliferation. Sunitinib reduced dose-dependently cell viability of both NCI-H295 and SW13 cells (SW13: 0.1 μM 96 ± 7%, 1 μM 90 ± 9%*, 5 μM 62 ± 6%*, controls 100 ± 9%; *p < 0.05). To determine sunitinib effects on steroidogenesis, we measured steroid hormones in cell culture supernatant by gas chromatography–mass spectrometry. We observed a pronounced decrease of cortisol secretion (1 μM 90.1 ± 1.5%*, 5 μM 57.2 ± 0.3%*, controls 100 ± 2.4%) and a concomitant increase in the DHEA/4-androstenedione and 17-hydroxypregnenolone/17-hydroxyprogesterone ratios, indicating specific inhibition of 3β-hydroxysteroid dehydrogenase (HSD3B2). In yeast microsomes transformed with HSD3B2, no direct inhibition of HSD3B2 by sunitinib was detected. Sunitinib induced down-regulation of HSD3B2 mRNA and protein in ACC cell lines (mRNA: 1 μM 44 ± 16%*; 5 μM 22 ± 2%*; 10 μM 19 ± 4%*; protein: 1 μM 82 ± 8%; 5 μM 63 ± 8%*; 10 μM 55 ± 9%*). CYP11B1 was down-regulated at mRNA but not at protein level and CYP11A1 remained unchanged. In conclusion, target molecules of sunitinib are expressed in the vast majority of ACC samples. Sunitinib exhibits anti-proliferative effects in vitro, and appears to specifically block adrenal steroidogenesis by down-regulation of HSD3B2, rendering it a promising option for treatment of ACC

17α-hydroxylase deficiency diagnosed in early infancy caused by a novel mutation of the CYP17A1 Gene

Mutations of the CYP17A1 gene cause 17α-hydroxylase deficiency (17OHD) resulting in 46,XY disorder of sex development, hypertension, hypokalemia and absent pubertal development. It is a rare, autosomal recessive form of congenital adrenal hyperplasia (CAH).We report on a neonate with prenatally determined 46,XY karyotype. At 20 weeks of gestation, lack of development of male external genitalia was noticed. A phenotypically female child was born at 41 weeks of gestation.Postnatal ultrasound revealed testes in both labia majora, an absence of uterus and normal adrenal glands. Steroid hormone analysis in serum revealed low basal levels of cortisol, testosterone and androstenedione in the presence of massively elevated corticosterone at the age of 2 weeks. The urinary steroid profile from spot urine showed excessive excretion of 17-desoxysteroids, decreased glucocorticoid metabolites and absent C19 steroids, thus proving 17OHD. Molecular analysis identified a novel mutation of the CYP17A1 gene: c.896T>A (p.I299N) in exon 5. Substitution with hydrocortisone was started. The child is raised as a girl and is developing well so far.Herein, we report the unusually early diagnosis of a newborn with the rare CAH form of 17OHD allowing an early start of treatment