NEW DEVELOPMENTS IN ALERT LEPROSY CONTROL PROGRAMME AND THE ISSUES OF INTEGRATION

ABSTRACTIntroduction of Multidrug Therapy (MDT), as recommended by the WHO in 1982, started in Shoa Administrative Region in the beginning of 1983. From the results of introduction of the new regimens in two districts in the north-eastern part of the region, it can be concluded that implementation of MDT for paucibacillary patients has proven to be successful and feasible. Implementation of MDT in Addis Ababa and two surrounding districts, which started in March 1984, gives so far very promising results. Essential requirements for successful implementation of MDT are discussed. Reasons are given for a continuously high workload, at least during the .first years after the majority of the patients have been released from chemotherapy. Integration of leprosy control with the general medical services should definitely be aimed at; however, integration should be carefully planned and timed. Implementation of MDT requires reorganization and upgrading of virtually all aspects of leprosy control. This asks for specialization as regard planning, organization and evaluation. Another aspect of integration is the combination of tuberculosis and leprosy. The leprosy control services could strengthen the tuberculosis services at the time laboratory services have been established and the initial phase of intensive treatment has been secured

Ageing Better in the Netherlands

The Dutch National Care for the Elderly Programme was an initiative organized by the Netherlands Organisation for Health Research and Development (ZonMw) between 2008 and 2016. The aim of the programme was to collect knowledge about frail elderly, to assess their needs and to provide person-centred and integrated care better suited to their needs. The budget of EUR 88 million was provided by the Dutch Ministry of Health, Welfare and Sports. Putting the needs of elderly people at the heart of the programme and ensuring their active participation were key to the programme’s success. The programme outcomes included the establishment of eight geriatric networks around the medical universities with 650 organisations and the completion of 218 projects. These projects, involving 43,000 elderly people and 8500 central caregivers, resulted in the completion of 45 PhD theses and the publication of more than 400 articles and the development of 300 practice toolkits, one database and a website, www.beteroud.nl. The Dutch National Care for the Elderly Programme has since developed into a movement and continues under the consortium Ageing Better, made up of eight organisations. Through the use of ambassadors, Ageing Better promotes the message that ageing is not a disease but a new phase of life

Resensitization of HTLV-1 infected T cells towards apoptosis by rocaglamide involves inhibition of protein translation

Human T cell Leukemia Virus Type 1 (HTLV-1) is a retrovirus, associated with several diseases including Adult T-cell Leukemia/Lymphoma (ATL). Because of apoptosis resistance treatment provides only limited benefits for ATL. CD95/CD95L-mediated apoptosis is an important mechanism of T cell homeostasis. We have previously shown that HTLV-1 infected T cells are more resistant to CD95L-induced apoptosis as compared to non HTLV-1 infected T cells. In this study we showed that HTLV-1 infected T cells are also resistant towards TRAIL, which suggests a general mechanism of resistance towards death receptor-mediated apoptosis. The basis of apoptotic resistance in HTLV-1 infected T cells was suggested to be due to the elevated expression of several anti-apoptotic proteins involved in modulation of the intrinsic cell death pathway. Recently our group further found that apoptosis is also blocked within the extrinsic cell death pathway by high c-FLIP expression. C-FLIP is an anti-apoptotic protein that blocks death receptor-mediated apoptosis at the DISC level. To overcome resistance, we have treated HTLV-1 infected T cells with CD95L or TRAIL in combination with an herbal compound, Rocaglamide, derived from a Traditional Chinese Medicinal plant (TCM). We showed that one of the Rocaglamide derivatives tested, Roc-AR, sensitizes HTLV-1 infected T cells towards CD95L- and TRAIL-mediated apoptosis via down-regulation of c-FLIP expression at the translational level. Further investigation of the molecular mechanisms by which Roc-AR suppresses c-FLIP translation, revealed a mechanism different from other known translation inhibitors. Roc-AR strongly inhibits the Ras pathway leading to the inhibition of Mnk-1, a protein kinase essential for the activation of the translation initiation factor 4E (eIF4E). Thus, blocking activation of eIF4E by Roc-AR leads to inhibition of cap-dependent eukaryotic translation at the initiation stage. Most importantly, Roc-AR does not sensitize normal peripheral blood T cells to CD95L-and TRAIL-induced apoptosis. Our study raises the possibility to develop Roc-AR as CD95L or TRAIL adjuvant for treatment of ATL and other types of T-cell tumors

Biologische Veehouderij en Management

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