Hi Tech Rec: Are We Losing the Real Pleasures of Life?

In this paper, the impact of advanced technology on the future and basic philosophy of leisure is analyzed from a quantitative and qualitative point of view. The marriage of science, technology, and leisure is examined in its present state and the implied conditions of the future. The inferences of newly emerging man-machine systems in the leisure industry are explored

Neue Inhibitoren der Amyloid-Aggregation als potentielle Therapeutika der Alzheimerschen Erkrankung

Statins are classically used in the treatment and prevention of hypercholesterolaemia due to their ability to inhibit the biosynthesis of cholesterol by blocking HMG-CoA-reductase, which is the rate limiting enzyme in cholesterol biosynthesis. Meanwhile, some studies have suggested the possible use of statins as potential therapeutics in the treatment of Alzheimer’s disease. Different pathways apart from their inhibitory activity on HMG-CoA-reductase have been explored. It has been shown that statins influence the release of β-amyloid, which aggregates to senile plaques, a pathological hallmark of AD. Although the mechanism has still not been fully discerned, it has been attributed to decreased cholesterol levels as well as decreased isoprenoid biosynthesis, which directly influences APP processing. NO-releasing substances have also been advocated to be of potential use in antidementive therapy due to their anti-inflammatory effect and their ability to improve the blood circulation. Notion behind this work was to determine the potential inhibitory effect of statins on β-amyloid-aggregation, as another possible pathway of their mode of action. Another goal was to prepare nitrate-statin-hybrid molecules in order to assess the extent to which the combination of these two promising pharmacophores would lead to a synergistic effect. Furthermore, some selected compounds were tested for their cholesterol-lowering and vasodilatory potencies to determine the influence of the structural modification on the biological activity. A novel nitratoacylated-stimvastatin derivative was obtained by cleaving the ester-side-chain, followed by selective protection of the lactonic alcohol and introduction of the nitrated-side-chain by acylation. Introduction of an organic nitrate to the simvastatin-scaffold resulted in only a slight decrease in the HMG-CoA-reductase inhibitory potency. In contrast, modification of the lactonic OH-group, which is crucial for inhibitory activity, either through acylation or elimination resulted in almost a complete loss of inhibitory potency. As expected all tested nitratoacylated compounds showed a vasodilatory effect. Since all tested derivatives encompass the same carrier molecule, the relaxation potency of the organic nitrates correlated with the number of nitrate groups in the molecule. In conclusion, the introduction of the bulky organic statin-scaffold did not result in a decrease of the vasodilatory potencies. A cell-free Aβ40-aggregation assay was successfully established, to investigate the possible direct effect of statin derivatives on β-amyloid-aggregation. For this purpose, the inhibitory activity of statins on Aβ40-aggregation was assessed as a function of the fluorescence of thioflavin T. The inhibitory activity, which was observed by the decrease of the measured fluorescence intensities, was further confirmed by electron microscopy

Management of elderly patients with acute promyelocytic leukemia: progress and problems

Despite substantial progress in the management and outcome of acute promyelocytic leukemia (APL) during the last decades, older age remains a prominent negative prognostic factor. The improvement of long-term stabilization and cure of older APL patients is therefore a particular challenge. Data of unselected population-based studies suggest a high rate of exclusion from clinical trials in older age. The comparison of registry and study data indicates that study patients represent a positive selection. Older APL patients seem as sensitive to therapy as younger patients. With conventional therapy, based on all-trans retinoic acid (ATRA) and chemotherapy, over 50 % of older APL patients can probably be cured. Special problems of advanced age are the high rate of early death before or during induction therapy and the high frequency of death in remission with negative influence on the outcome. Both may be related in part to a higher vulnerability against the common treatment with ATRA and chemotherapy. Alternative less toxic approaches including arsenic trioxide (ATO) with or without ATRA and combinations with gemtuzumab ozogamicin or with reduced chemotherapy can induce long-lasting remission in all stages of APL. Considering the high curative potential and the excellent tolerance of ATO in newly diagnosed and relapsed APL, older patients are probably a particular target group for a chemotherapy-free approach with ATO

Outcome of older (≥70 years) APL patients frontline treated with or without arsenic trioxide-an International Collaborative Study

Data on outcome in older (≥70 years) patients with acute promyelocytic leukemia after treatment with arsenic trioxide (ATO) compared with standard chemotherapy (CTX) is scarce. We evaluated 433 patients (median age, 73.4 years) treated either with ATO+ all-trans retinoic acid (ATO/ATRA; n = 26), CTX/ATRA + ATO during consolidation (CTX/ATRA/ATO; n = 148), or with CTX/ATRA (n = 259). Median follow-up for overall survival (OS) was 4.8 years. Complete remissions (CR) were achieved in 92% with ATO/ATRA and 82% with CTX/ATRA; induction death rates were 8% and 18%, respectively. For analysis of postremission outcomes we combined the ATO/ATRA and CTX/ATRA/ATO groups (ATO/ATRA ± CTX). Cumulative incidence of relapse (CIR) was significantly lower after ATO/ATRA ± CTX compared with CTX/ATRA (P 10 × 10 9 /l) white blood cell (WBC) counts at diagnosis were associated with higher CIR (P < 0.001) compared with lower WBC in the CTX/ATRA group, but not in the ATO/ATRA ± CTX group (P = 0.48). ATO, when added to ATRA or CTX/ATRA is feasible and effective in elderly patients for remission induction and consolidation, particularly in patients with high WBC at diagnosis

The treatment of polycythaemia vera: an update in the JAK2 era

The clinical course of polycythaemia vera is marked by a high incidence of thrombotic complications, which represent the main cause of morbidity and mortality. Major predictors of vascular events are increasing age and previous thrombosis. Myelosuppressive drugs can reduce the rate of thrombosis, but there is concern that their use raises the risk of transformation into acute leukaemia. To tackle this dilemma, a risk-oriented management strategy is recommended. Low-risk patients should be treated with phlebotomy and low-dose aspirin. Cytotoxic therapy is indicated in high-risk patients, with the drug of choice being hydroxyurea because its leukaemogenicity is low. The recent discovery of JAK2 V617F mutation in the vast majority of polycythaemia vera patients opens new avenues for the treatment of this disease. Novel therapeutic options theoretically devoid of leukaemic risk, such as alpha-interferon and imatinib, affect JAK2 expression in some patients. Nevertheless, these drugs require further clinical experience and, for the time being, should be reserved for selected cases