Efficacy of Fumaric Acid Esters in the R6/2 and YAC128 Models of Huntington's Disease

Huntington's disease (HD) is an autosomal dominantly inherited progressive neurodegenerative disease. The exact sequel of events finally resulting in neurodegeneration is only partially understood and there is no established protective treatment so far. Some lines of evidence speak for the contribution of oxidative stress to neuronal tissue damage. The fumaric acid ester dimethylfumarate (DMF) is a new disease modifying therapy currently in phase III studies for relapsing-remitting multiple sclerosis. DMF potentially exerts neuroprotective effects via induction of the transcription factor “nuclear factor E2-related factor 2” (Nrf2) and detoxification pathways. Thus, we investigated here the therapeutic efficacy of DMF in R6/2 and YAC128 HD transgenic mice which mimic many aspects of HD and are characterized by an enhanced generation of free radicals in neurons. Treatment with DMF significantly prevented weight loss in R6/2 mice between postnatal days 80–90. At the same time, DMF treatment led to an attenuated motor impairment as measured by the clasping score. Average survival in the DMF group was 100.5 days vs. 94.0 days in the placebo group. In the histological analysis on day 80, DMF treatment resulted in a significant preservation of morphologically intact neurons in the striatum as well as in the motor cortex. DMF treatment resulted in an increased Nrf2 immunoreactivity in neuronal subpopulations, but not in astrocytes. These beneficial effects were corroborated in YAC128 mice which, after one year of DMF treatment, also displayed reduced dyskinesia as well as a preservation of neurons. In conclusion, DMF may exert beneficial effects in mouse models of HD. Given its excellent side effect profile, further studies with DMF as new therapeutic approach in HD and other neurodegenerative diseases are warranted

Targeting Huntington’s disease through histone deacetylases

Huntington’s disease (HD) is a debilitating neurodegenerative condition with significant burdens on both patient and healthcare costs. Despite extensive research, treatment options for patients with this condition remain limited. Aberrant post-translational modification (PTM) of proteins is emerging as an important element in the pathogenesis of HD. These PTMs include acetylation, phosphorylation, methylation, sumoylation and ubiquitination. Several families of proteins are involved with the regulation of these PTMs. In this review, I discuss the current evidence linking aberrant PTMs and/or aberrant regulation of the cellular machinery regulating these PTMs to HD pathogenesis. Finally, I discuss the evidence suggesting that pharmacologically targeting one of these protein families the histone deacetylases may be of potential therapeutic benefit in the treatment of HD

Milieuhygienische kwaliteit van primaire en secundaire bouwmaterialen in relatie tot hergebruik en bodem- en oppervlaktewaterenbescherming

To support the General Administrative Order on Construction Materials (Soil and Surface Waters Protection) this document supplies information on: 1) the quantification of the standard values for the application of construction materials ; 2) the environmental quality (characterization) of construction materials ; ; 3) the consequenses for use and re-use of construction materials.Ter ondersteuning van het Bouwstoffenbesluit (Bodem en Oppervlaktewateren Bescherming) levert dit rapport de volgende informatie: 1) de bepaling van de normwaarden voor het gebruik van bouwmaterialen ; 2) de milieukwaliteit (karakterisering) van de bouwmaterialen ; 3) het resultaat voor het gebruik en het hergebruik van bouwmaterialen

[Environmental quality of primary and secondary building materials in relation to re-use, soil protection and surface waters protection. Appendix A, B en C]

Tevens RIZA rapportnr. 93.042.<br>Ter ondersteuning van het Bouwstoffenbesluit (Bodem en Oppervlaktewateren Bescherming) levert dit rapport de volgende informatie: 1) de bepaling van de normwaarden voor het gebruik van bouwmaterialen ; 2) de milieukwaliteit (karakterisering) van de bouwmaterialen ; 3) het resultaat voor het gebruik en het hergebruik van bouwmaterialen.This report supports the General Administrative Order on Building Materials (Soil- and Surface Waters Protection). The report supplies information on: - The quantification of the standard values for the application of building materials. - The environmental quality (characterization) of building materials. - The consequences for use and re-use of building materials.DGM/B

Milieuhygienische kwaliteit van primaire en secundaire bouwmaterialen in relatie tot hergebruik en bodem- en oppervlaktewaterenbescherming

Ter ondersteuning van het Bouwstoffenbesluit (Bodem en Oppervlaktewateren Bescherming) levert dit rapport de volgende informatie: 1) de bepaling van de normwaarden voor het gebruik van bouwmaterialen ; 2) de milieukwaliteit (karakterisering) van de bouwmaterialen ; 3) het resultaat voor het gebruik en het hergebruik van bouwmaterialen.To support the General Administrative Order on Construction Materials (Soil and Surface Waters Protection) this document supplies information on: 1) the quantification of the standard values for the application of construction materials ; 2) the environmental quality (characterization) of construction materials ; ; 3) the consequenses for use and re-use of construction materials.DGM/B

[Environmental quality of primary and secondary building materials in relation to re-use, soil protection and surface waters protection.]

This report supports the General Administrative Order on Building Materials (Soil- and Surface Waters Protection). The report supplies information on: - The quantification of the standard values for the application of building materials. - The environmental quality (characterization) of building materials. - The consequences for use and re-use of building materials.Ter ondersteuning van het Bouwstoffenbesluit (Bodem en Oppervlaktewateren Bescherming) levert dit rapport de volgende informatie: 1) de bepaling van de normwaarden voor het gebruik van bouwmaterialen ; 2) de milieukwaliteit (karakterisering) van de bouwmaterialen ; 3) het resultaat voor het gebruik en het hergebruik van bouwmaterialen

Environmental quality of primary and secundary construction materials in relation to re-use and protection of soil and surface water

Ter ondersteuning van het Bouwstoffenbesluit (Bodem en Oppervlaktewateren Bescherming) levert dit rapport de volgende informatie: 1) de bepaling van de normwaarden voor het gebruik van bouwmaterialen ; 2) de milieukwaliteit (karakterisering) van de bouwmaterialen ; 3) het resultaat voor het gebruik en het hergebruik van bouwmaterialen.<br

Life cycle assessment of pyrolysis-gasification as an emerging municipal solid waste treatment technology

Waste-to-energy technologies are considered as one of the key waste treatment technologies due to their energy and heat recovery efficiencies from the waste. A number of research studies were accomplished to understand the potential environmental burdens from emerging waste treatment technologies such as pyrolysis-gasification (PG). The aim of this study was to examine the PG of municipal solid waste (MSW) treatment process through a life cycle assessment (LCA) method. The study also includes a comparative LCA model of PG and incineration to identify the potential environmental burdens from the existing (incineration) and emerging (PG) waste treatment technologies. This study focused on ten environmental impact categories under two different scenarios, namely: (a) LCA model of PG and (b) comparative LCA model of PG and incineration. The scenario (a) showed that PG had significant environmental burdens in the aquatic eco-toxicity and the global warming potential impact categories. The comparative scenario (b) of PG and incineration of MSW showed that PG had comparatively lower potential environmental burdens in acidification, eutrophication, and aquatic eco-toxicity. Both LCA models showed that the environmental burdens were mainly caused by the volume of the thermal gas (emissions) produced from these two technologies and the final residue to disposal. Therefore, the results indicate that the efficiency and environmental burdens of the emerging technologies are dependent on the emissions and the production of final residue to the landfill