Sauerstoffverbrauch und Alterung in Langzeitkulturen von Linsenepithel

Zusammenfassung Mit Hilfe der beschriebenen Technik gelang es, Linsenepithelien über 40 Passagen zu züchten; zugleich fanden morphologische Alterungsveränderungen und Sauerstoffverbrauch der Zellen im Warburg-Apparat Beachtung. Vergleichbare Untersuchungen sind derzeit nicht bekannt. Morphologisch überwogen Alterationen wie Vergrößerung des Zelleibes neben bekannten Degenerationszeichen. Der Sauerstoffverbrauch von 2 l pro Stunde pro 10⁵ Zellen zeigte sich in konstanter Höhe bis zur 39. Passage und sank dann abrupt auf etwa ein Viertel. Nachdem die Zellen ohne ersichtlichen Grund danach plötzlich starben, liegt die Folgerung nahe, daß der aerobe Stoffwechsel der Linsenepithelien unabhängig von ihrem Alter und ohne sich signifikant abzeichnenden Tagesrhythmus mit ihrem Überleben verbunden erscheint.

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Oxygen consumption and aging in longterm cultures of lens epithelia

By means of the described technique lens epithelia were cultured in 40 subcultures; at the same time, both the morphological aging processes and oxygen consumption of the cells, were observed using the Warburg respirometer. To date comparable studies are not available. Morphologically, cell enlargement took place in conjunction with signs of degeneration. Oxygen consumption of 2 l per hour per 10⁵ cells ±0.8 remained at a constant level without any significant diurnal rhythm up to subculture 39 and then suddenly fell to about one-fourth of the initial value. As the cells died of an unknown cause, it was concluded that the aerobic metabolism of lens epithelia seemed to be linked to survival without being age related.

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Herrn Prof. Dr. E. Schreck, dem damaligen Direktor der Klinik, in Dankbarkeit zum 70. Geburtstag     

Circulating growth factor levels are associated with tumorigenesis in neurofibromatosis type 1.

PURPOSE: Neurofibromatosis type 1 (NF1) is characterized by systemic development of neurofibromas. Early clinical diagnosis can be ambiguous, and genetic diagnosis can be prohibitively difficult. Dysregulation of a number of growth factors has been suggested to be a mechanism of pathogenesis. This study was performed to assess the contribution of circulating growth factors for diffuse tumorigenesis and the diagnostic value of circulating growth factor identification in serum. EXPERIMENTAL DESIGN: The growth stimulation of neurofibroma-derived cells by serum from NF1 patients was tested, and serum growth factor levels in a cohort of NF1 patients (n = 39) between the ages of 7 and 70 years were analyzed. RESULTS: Concentrations of midkine (MK) and stem cell factor, but not epidermal growth factor, were substantially increased in serum of NF1 patients when compared with healthy controls. Within the NF1 group, MK levels increased dramatically at puberty from an average of 0.79 ng/mL in patients <18 years to 1.18 ng/mL in patients >18 years old. Stem cell factor and MK concentrations above a defined threshold in serum of NF1 patients are of diagnostic benefit for 96% of patients in the cohort tested. Furthermore, serum from NF1 patients enhanced proliferation of human neurofibroma-derived primary Schwann cells and endothelial cells substantially better than normal serum. CONCLUSIONS: Enhanced circulating growth factor levels contribute to diffuse tumorigenesis in NF1 and may provide the basis for molecular diagnosis.     

Analysis of concerted expression of angiogenic growth factors in acute myeloid leukemia: expression of angiopoietin-2 represents an independent prognostic factor for overall survival.

PURPOSE: Bone marrow neoangiogenesis plays an important pathogenetic and possible prognostic role in acute myeloid leukemia (AML). Members of the vascular endothelial growth factor (VEGF) and angiopoietin family represent the most specific inducers of angiogenesis secreted by AML blasts. We therefore correlated expression of angiogenic factors with clinical variables. PATIENTS AND METHODS: We investigated the expression of VEGF-A, VEGF-C, angiopoietin-1 (Ang1), angiopoietin-2 (Ang2), and the receptor Tie2 by quantitative polymerase chain reaction in a cohort of 90 patients younger than 61 years with de novo AML entered into the German AML Süddeutsche H?moblastose Gruppe Hannover 95 trial. Uni- and multivariate analyses were performed using clinical and gene expression variables. RESULTS: Univariate analysis of overall survival indicated the following variables as prognostic factors: good response on a day-15 bone marrow examination after initiation of induction chemotherapy, karyotype, and high Ang2 expression. In multivariate analysis, only bad response and log Ang2 expression remained of statistical significance, with a hazard ratio of 3.51 (95% CI, 1.91 to 6.47) and 0.75 (95% CI, 0.61 to 0.91), respectively. Subgroup analysis suggested that the prognostic impact of Ang2 expression was especially evident in cohorts with low VEGF-C and Ang1 mRNA levels. CONCLUSION: These results show that expression of Ang2 represents an independent prognostic factor in AML. Additional research into interactions of angiogenic cytokines in the pathogenesis of bone marrow angiogenesis in AML is warranted.     

Is prevention of atopic eczema with hydrolyzed formulas cost-effective? A health economic evaluation from Germany

To cite this article: Mertens J, Stock S, Lüngen M, Berg AV, Kr?mer U, Filipiak-Pittroff B, Heinrich J, Koletzko S, Grübl A, Wichmann H-E, Bauer C-P, Reinhardt D, Berdel D, Gerber A. Is Prevention of Atopic Eczema with Hydrolyzed Formulas Cost-Effective? A Health Economic Evaluation from Germany. Pediatr Allergy Immunol 2012: 23: 597-604. ABSTRACT: Objective: The German Infant Nutritional Intervention (GINI) trial, a prospective, randomized, double-blind intervention, enrolled children with a hereditary risk for atopy. When fed with certain hydrolyzed formulas for the first 4?months of life, the risk was reduced by 26-45% in PP and 8-29% in intention-to-treat (ITT) analyses compared with children fed with regular cow's milk at age 6. The objective was to assess the cost-effectiveness of feeding hydrolyzed formulas. Patients and Methods: Cost-effectiveness was assessed with a decision tree model programmed in TreeAge. Costs and effects over a 6-yr period were analyzed from the perspective of the German statutory health insurance (SHI) and a societal perspective at a 3% effective discount rate followed by sensitivity analyses. Results: The extensively hydrolyzed casein formula would be the most cost-saving strategy with savings of 478?€ per child treated in the ITT analysis (CI95%: 12?€; 852?€) and 979?€ in the PP analysis (95%CI: 355?€; 1455?€) from a societal perspective. If prevented cases are considered, the partially whey hydrolyzed formula is cost-saving (ITT -5404?€, PP -6358?€). From an SHI perspective, the partially whey hydrolyzed formula is cost-effective, but may also be cost-saving depending on the scenario. An extensively hydrolyzed whey formula also included into the analysis was dominated in all analyses. Conclusions: For the prevention of AE, two formulas can be cost-effective or even cost-saving. We recommend that SHI should reimburse formula feeding or at least the difference between costs for cow's milk formula and the most cost-effective formula.