Lack of influence of the COX inhibitors metamizol and diclofenac on platelet GPIIb/IIIa and P-selectin expression in vitro

BACKGROUND: The effect of non-steroidal anti-inflammatory drugs (NSAIDs) for reduced platelet aggregation and thromboxane A(2 )synthesis has been well documented. However, the influence on platelet function is not fully explained. Aim of this study was to examine the influence of the COX-1 inhibiting NSAIDs, diclofenac and metamizol on platelet activation and leukocyte-platelet complexes, in vitro. Surface expression of GPIIb/IIIa and P-selectin on platelets, and the percentage of platelet-leukocyte complexes were investigated. METHODS: Whole blood was incubated with three different concentrations of diclofenac and metamizol for 5 and 30 minutes, followed by activation with TRAP-6 and ADP. Rates of GPIIb/IIIa and P-selectin expression, and the percentage of platelet-leukocyte complexes were analyzed by a flow-cytometric assay. RESULTS: There were no significant differences in the expression of GPIIb/IIIa and P-selectin, and in the formation of platelet-leukocyte complexes after activation with ADP and TRAP-6, regarding both the time of incubation and the concentrations of diclofenac and metamizol. CONCLUSIONS: Accordingly, the inhibitory effect of diclofenac and metamizol on platelet aggregation is not related to a reduced surface expression of P-selectin and GPIIb/IIIa on platelets

Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and susceptibility to pediatric acute lymphoblastic leukemia in a German study population

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) has a major impact on the regulation of the folic acid pathway due to conversion of 5,10-methylenetetrahydrofolate (methylene-THF) to 5-methyl-THF. Two common polymorphisms (677C>T and 1298A>C) in the gene coding for MTHFR have been shown to reduce MTHFR enzyme activity and were associated with the susceptibility to different disorders, including vascular disease, neural tube defects and lymphoid malignancies. Studies on the role of these polymorphisms in the susceptibility to acute lymphoblastic leukemia (ALL) led to discrepant results. METHODS: We retrospectively evaluated the association of the MTHFR 677C>T and 1298A>C polymorphisms with pediatric ALL by genotyping a study sample of 443 ALL patients consecutively enrolled onto the German multicenter trial ALL-BFM 2000 and 379 healthy controls. We calculated odds ratios of MTHFR genotypes based on the MTHFR 677C>T and 1298A>C polymorphisms to examine if one or both of these polymorphisms are associated with pediatric ALL. RESULTS: No significant associations between specific MTHFR variants or combinations of variants and risk of ALL were observed neither in the total patient group nor in analyses stratified by gender, age at diagnosis, DNA index, immunophenotype, or TEL/AML1 rearrangement. CONCLUSION: Our findings suggest that the MTHFR 677C>T and 1298A>C gene variants do not have a major influence on the susceptibility to pediatric ALL in the German population

Seasonal and inter-annual climate forecasting: The new tool for increasing preparedness to climate variability and change in agricultural planning and operations

Climate variability and change affects individuals and societies. Within agricultural systems, seasonal climate forecasting can increase preparedness and lead to better social, economic and environmental outcomes. However, climate forecasting is not the panacea to all our problems in agriculture. Instead, it is one of many risk management tools that sometimes play an important role in decision-making. Understanding when, where and how to use this tool is a complex and multi-dimensional problem. To do this effectively, we suggest a participatory, cross-disciplinary research approach that brings together institutions (partnerships), disciplines (e.g., climate science, agricultural systems science, rural sociology and many other disciplines) and people (scientist, policy makers and direct beneficiaries) as equal partners to reap the benefits from climate knowledge. Climate science can provide insights into climatic processes, agricultural systems science can translate these insights into management options and rural sociology can help determine the options that are most feasible or desirable from a socio-economic perspective. Any scientific breakthroughs in climate forecasting capabilities are much more likely to have an immediate and positive impact if they are conducted and delivered within such a framework. While knowledge and understanding of the socio-economic circumstances is important and must be taken into account, the general approach of integrated systems science is generic and applicable in developed as well as in developing countries. Examples of decisions aided by simulation output ranges from tactical crop management options, commodity marketing to policy decisions about future land use. We also highlight the need to better understand temporal- and spatial-scale variability and argue that only a probabilistic approach to outcome dissemination should be considered. We demonstrated how knowledge of climatic variability (CV), can lead to better decisions in agriculture, regardless of geographical location and socio-economic conditions