Age-related changes of apoptotic cell death in human lymphocytes

Apoptosis seems to be involved in immunosenescence associated with aging. Moreover, in lymphocytes (PBL) of patients with Alzheimer's disease, an increased susceptibility to the apoptotic pathway has been described possibly due to impaired protection of oxidative stress. Accordingly, it seemed to be of particular interest to investigate the contribution of normal aging to the susceptibility from human lymphocytes to programmed cell death. We could show that PBL from elderly individuals (>60 years) accumulate apoptosing cells to a significant higher extent in spontaneous and activation-induced cell death compared to younger controls (<35 years). Treatment with the oxidative stressor 2-deoxy-D-ribose or with agonistic-CD95-antibody pronounced this effect even more implicating a higher sensitivity to reactive oxygen species and a higher functional CD95 expression, respectively. In addition, expression of the activation markers HLA-DR and CD95 was significantly increased in CD3+-cells of aged subjects, while expression of CD25 did not seem to be affected by age. Expression of Bcl-2 was increased in aging and correlated with the number of apoptotic cells

Age-related increase of oxidative stress-induced apoptosis in mice prevention by Ginkgo biloba extract (EGb761)

Enhanced apoptosis and elevated levels of reactive oxygen species (ROS) play a major role in aging. In addition, several neurodegenerative diseases are associated with increased oxidative stress and apoptosis in neuronal tissue. Antioxidative treatment has neuro-protective effects. The aim of the present study was to evaluate changes of susceptibility to apoptotic cell death by oxidative stress in aging and its inhibition by the antioxidant Ginkgo biloba extract EGb761. We investigated basal and ROS-induced levels of apoptotic lymphocytes derived from the spleen in young (3 months) and old (24 months) mice. ROS were induced by 2-deoxy-D-ribose (dRib) that depletes the intracellular pool of reduced glutathione. Lymphocytes from aged mice accumulate apoptotic cells to a significantly higher extent under basal conditions compared to cells from young mice. Treatment with dRib enhanced this difference, implicating a higher sensitivity to ROS in aging. Apoptosis can be reduced in vitro by treatment with EGb761. In addition, mice were treated daily with 100mg/kg EGb761 per os over a period of two weeks. ROS-induced apoptosis was significantly reduced in the EGb761 group. Interestingly, this effect seemed to be more pronounced in old mice

Der Einsatz von Lernstrategien in einer konkreten Lernsituation bei Schülern unterschiedlicher Jahrgangsstufen

Der Beitrag ist darauf ausgelegt, jeweils einen Ansatzpunkt zur Optimierung von Erziehungsanstrengungen zu benennen und die Wirksamkeit der vorgeschlagenen Maßnahmen empirisch zu belegen ... . Die Autoren untersuchen die Verwendung selbstregulatorischer Lernstrategien in unterschiedlichen Jahrgangsstufen. Dabei legen sie ihren Schwerpunkt zunächst auf die Analyse der Veränderung des Lernstrategieeinsatzes im Zeitverlauf und die Beziehungen zwischen Lernerfolg und Strategieeinsatz. (DIPF/Orig.

Effects of EGb 761® Ginkgo biloba extract on mitochondrial function and oxidative stress

As major sources of reactive oxygen species (ROS), mitochondrial structures are exposed to high concentrations of ROS and may therefore be particularly susceptible to oxidative damage. Mitochondrial damage could play a pivotal role in the cell death decision. A decrease in mitochondrial energy charge and redox state, loss of transmembrane potential (depolarization), mitochondrial respiratory chain impairment, and release of substances such as calcium and cytochrome c all contribute to apoptosis. These mitochondrial abnormalities may constitute a part of the spectrum of chronic oxidative stress in Alzheimer's disease. Accumulation of amyloid beta (Abeta) in form of senile plaques is also thought to play a central role in the pathogenesis of Alzheimer's disease mediated by oxidative stress. In addition, increasing evidence shows that Abeta generates free radicals in vitro, which mediate the toxicity of this peptide. In our study, PC12 cells were used to examine the protective features of EGb 761(definition see editorial) on mitochondria stressed with hydrogen peroxide and antimycin, an inhibitor of complex III. In addition, we investigated the efficacy of EGb 761 in Abeta-induced MTT reduction in PC12 cells. Moreover, we examined the effects of EGb 761 on ROS levels and ROS-induced apoptosis in lymphocytes from aged mice after in vivo administration. Here, we will report that EGb 761 was able to protect mitochondria from the attack of hydrogen peroxide, antimycin and Abeta. Furthermore, EGb 761 reduced ROS levels and ROS-induced apoptosis in lymphocytes from aged mice treated orally with EGb 761 for 2 weeks. Our data further emphasize neuroprotective properties of EGb 761, such as protection against Abeta-toxicity, and antiapoptotic properties, which are probably due to its preventive effects on mitochondria

Self-regulated learning as self-regulation of learning strategies - A training experiment on leaming from texts

Insgesamt 69 Berufstätige nahmen an vier Tagen an einem aus vier Modulen bestehenden computer-basierten Training zum selbstregulierten Lernen aus Texten teil. Gegenstand der Trainingsmodule waren Lernstrategien zur Erfüllung der vier Klauer\u27schen Lehrfunktionen Motivation, Information, Informationsverarbeitung sowie Steuerung und Kontrolle. Je nach Zugehörigkeit zur experimentell variierten Trainingsbedingung erhielten die Versuchspersonen bei jedem Modul (1) kein spezifisches Training, (2) nur ein Training der Lernstrategie oder (3) ein kombiniertes Training der Lernstrategie und darauf bezogener Selbstregulation. Zur Erfassung der anfänglichen Lesekompetenz bearbeiteten die Versuchspersonen vor Beginn des Trainings einen Lehrtext sowie einen zugehörigen lehrzielorientierten Test. Nach jedem Trainingsmodul bearbeiteten sie zur Anwendung der Trainingsinhalte ebenfalls einen Lehrtext, und es wurde ebenfalls anhand eines lehrzielorientierten Tests erhoben, wie viel Wissen sie aus der Bearbeitung des Textes gewonnen hatten. Die Teilnehmer des kombinierten Trainings schnitten im Vortest-Nachtest-Vergleich deutlich besser ab als die Teilnehmer des Lernstrategietrainings und als die Teilnehmer der Kontrollbedingung ohne Training. Die im Rahmen dieses Trainingsansatzes erzielten Ergebnisse entsprechen aktuellen Theorien des Trainings von Lernstrategien, die davon ausgehen, dass es sinnvoll ist, neben der Vermittlung von Wissen über einzelne Lernstrategien auch den zielführenden Einsatz der jeweiligen Lernstrategie mit zu trainieren. (ZPID

Reduced antioxidant enzyme activity in brains of mice transgenic for human presenilin-1 with single or multiple mutations

Alzheimer's disease-related mutations in the presenilin-1 gene (PS1) are leading to an elevated production of neurotoxic beta-amyloid 1-42 and may additionally enhance oxidative stress. Here, we provide in vivo evidence indicating that brains of transgenic mice expressing different human Alzheimer-linked PS1 mutations exhibit a reduced activity of two antioxidant enzymes. For this purpose, mice transgenic for human PS1 and for single and multiple PS1 mutations were generated. Mice with multiple PS1 mutations showed a significantly decreased activity of the antioxidant enzymes Cu/Zn superoxide dismutase and glutathione reductase already at an age of 3-4 months. As expected, this effect was less pronounced for the mice with a single PS1 mutation. By contrast, animals bearing normal human PS1 showed significantly elevated enzyme activities relative to non-transgenic littermate controls

Pathology of disappearing bone disease: a case report with immunohistochemical study.

A case of disappearing bone disease of the proximal femur is reported with histopathological and immunohistochemical studies. There was a densely packed cellular tissue, positive to endothelial antibodies, in areas of massive bone destruction. A more differentiated vascular tissue was present where trabecular cancellous or cortical bone was preserved with only focal zones of accelerated bone remodelling. The self-limited course correlates well with two phases of evolution of the histopathological lesions with neoplastic-like proliferation of endothelial cells corresponding to the rapid and massive bone destruction, and a later differentiation of the cells in mature vascular structures, but still with accelerated bone resorption which is partly compensated by appositional activity