Um dieser Herausforderung entgegentreten zu können, wurde „Drink Smart“, eine Active & Assisted Living- Lösung, entwickelt. Das zweite Ziel — ebenfalls unter Performanz fallend — war die ...Kommunikation des Drink Smart Systems mit einer elektronischen Pflegedokumentation bzw. das Angebot einer Stand-Alone-Lösung mithilfe einer Smartphone Applikation. Für die Evaluation der Projektziele wurden den Überkategorien Forschungsfragen zugeordnet, beispielsweise _ Welche technische Performanz erreicht das Drink Smart System im Alltag und in der Nutzung durch die Zielgruppen? _ Welche Funktionalitäten konnten bzw. konnten nicht umgesetzt werden? _ Welche technische Performanz erreicht das System in einer praxisnahen Anwendung? _ Welche Probleme können in der Gebrauchstauglichkeit während des Pre-Trails identifiziert werden? _ Welche Usability-Probleme bzw. Während der Pre-Trials fand eine heuristische Evaluation durch eine Expertin in Bezug auf die Usability sowie eine Testung auf Stabilität, Funktionalität und Einsatzsicherhit durch Projektmitarbeiter der Fachhochschule Campus Wien (FHCW) und der MIK — mobile, individuelle Krankenpflege -OG statt.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Succinate dehydrogenase (SDH) has been associated with carcinogenesis in pheochromocytoma and paraganglioma. In the present study we investigated components of the oxidative phosphorylation system in ...human neuroblastoma tissue samples.
Spectrophotometric measurements, immunohistochemical analysis and Western blot analysis were used to characterize the aerobic mitochondrial energy metabolism in neuroblastomas (NB).
Compared to mitochondrial citrate synthase, SDH activity was severely reduced in NB (n = 14) versus kidney tissue. However no pathogenic mutations could be identified in any of the four subunits of SDH. Furthermore, no genetic alterations could be identified in the two novel SDH assembly factors SDHAF1 and SDH5. Alterations in genes encoding nfs-1, frataxin and isd-11 that could lead to a diminished SDH activity have not been detected in NB.
Because downregulation of other complexes of the oxidative phosphorylation system was also observed, a more generalized reduction of mitochondrial respiration seems to be present in neuroblastoma in contrast to the single enzyme defect found in hereditary pheochromocytomas.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Warburg theory of cancer postulates that an important driver of tumorigenesis is insufficient respiration due to mitochondrial defects, and concomitant enhancement of lactate production due to ...increased aerobic glycolysis. We analysed 48 melanoma samples by immunohistochemistry and found that 38% of melanomas are characterized by areas of isolated or combined deficiencies of complexes of the oxidative phosphorylation (OXPHOS) system, whereby the incidence of OXPHOS‐deficient areas is associated with an increased Breslow index; 62% of melanomas showed high expression of all OXPHOS complexes. Expression of carbonic anhydrase IX was low, indicating that melanomas generally are well‐oxygenated. Expression of HIF‐1α and MCT4 was high, which might be a consequence of increased lactate dehydrogenase A levels in melanomas. Our data indicate that there are two types of melanomas: one that features a classic Warburg effect, whereas the other one, despite being glycolytic, maintains a high level of OXPHOS complexes.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
MYCN-amplification in high-grade Neuroblastoma (NB) tumors correlates with increased vascularization and therapy resistance. This study combines an anti-angiogenic approach with targeting NB ...metabolism for treatment.
Metronomic cyclophosphamide (MCP) monotherapy significantly inhibited NB growth and prolonged host survival. Growth inhibition was more pronounced in MYCN-amplified xenografts. Immunohistochemical evaluation of this subtype showed significant decrease in blood vessel density and intratumoral hemorrhage accompanied by blood vessel maturation and perivascular fibrosis. Up-regulation of VEGFA was not sufficient to compensate for the effects of the MCP regimen. Reduced Bcl-2 expression and increased caspase-3 cleavage were evident. In contrast non MYCN-amplified tumors developed resistance, which was accompanied by Bcl-2-up-regulation. Combining MCP with a ketogenic diet and/or calorie-restriction significantly enhanced the anti-tumor effect. Calorie-restricted ketogenic diet in combination with MCP resulted in tumor regression in all cases.
Our data show efficacy of combining an anti-angiogenic cyclophosphamide dosing regimen with dietary intervention in a preclinical NB model. These findings might open a new front in NB treatment.
The human placenta, a tissue with a lifespan limited to the period of pregnancy, is exposed to varying shear rates by maternal blood perfusion depending on the stage of development. In this study, we ...aimed to investigate the effects of fluidic shear stress on the human trophoblast transcriptome and metabolism. Based on a trophoblast cell line cultured in a fluidic flow system, changes caused by shear stress were analyzed and compared to static conditions. RNA sequencing and bioinformatics analysis revealed an altered transcriptome and enriched gene ontology terms associated with amino acid and mitochondrial metabolism. A decreased GLUT1 expression and reduced glucose uptake, together with downregulated expression of key glycolytic rate-limiting enzymes, hexokinase 2 and phosphofructokinase 1 was observed. Altered mitochondrial ATP levels and mass spectrometry data, suggested a shift in energy production from glycolysis towards mitochondrial oxidative phosphorylation. This shift in energy production could be supported by increased expression of glutamic-oxaloacetic transaminase variants in response to shear stress as well as under low glucose availability or after silencing of GLUT1. The shift towards amino acid metabolic pathways could be supported by significantly altered amino acid levels, like glutamic acid, cysteine and serine. Downregulation of GLUT1 and glycolytic rate-limiting enzymes, with concomitant upregulation of glutamic-oxaloacetic transaminase 2 was confirmed in first trimester placental explants cultured under fluidic flow. In contrast, high fluid shear stress decreased glutamic-oxaloacetic transaminase 2 expression in term placental explants when compared to low flow rates. Placental tissue from pregnancies with intrauterine growth restriction are exposed to high shear rates and showed also decreased glutamic-oxaloacetic transaminase 2, while GLUT1 was unchanged and glycolytic rate-limiting enzymes showed a trend to be upregulated. The results were generated by using qPCR, immunoblots, quantification of immunofluorescent pictures, padlock probe hybridization, mass spectrometry and FRET-based measurement. Our study suggests that onset of uteroplacental blood flow is accompanied by a shift from a predominant glycolytic- to an alternative amino acid converting metabolism in the villous trophoblast. Rheological changes with excessive fluidic shear stress at the placental surface, may disrupt this alternative amino acid pathway in the syncytiotrophoblast and could contribute to intrauterine growth restriction.
PDF
