Antiplasmodial Activity of Nitroaromatic Compounds : Correlation with Their Reduction Potential and Inhibitory Action on Plasmodium falciparum Glutathione Reductase

With the aim to clarify the mechanism(s) of action of nitroaromatic compounds against the malaria parasite Plasmodium falciparum, we examined the single-electron reduction by P. falciparum ferredoxin:NADP+ oxidoreductase (PfFNR) of a series of nitrofurans and nitrobenzenes (n = 23), and their ability to inhibit P. falciparum glutathione reductase (PfGR). The reactivity of nitroaromatics in PfFNR-catalyzed reactions increased with their single-electron reduction midpoint potential (E17). Nitroaromatic compounds acted as non- or uncompetitive inhibitors towards PfGR with respect to NADPH and glutathione substrates. Using multiparameter regression analysis, we found that the in vitro activity of these compounds against P. falciparum strain FcB1 increased with their E17 values, octanol/water distribution coefficients at pH 7.0 (log D), and their activity as PfGR inhibitors. Our data demonstrate that both factors, the ease of reductive activation and the inhibition of PfGR, are important in the antiplasmodial in vitro activity of nitroaromatics. To the best of our knowledge, this is the first quantitative demonstration of this kind of relationship. No correlation between antiplasmodial activity and ability to inhibit human erythrocyte GR was detected in tested nitroaromatics. Our data suggest that the efficacy of prooxidant antiparasitic agents may be achieved through their combined action, namely inhibition of antioxidant NADPH:disulfide reductases, and the rapid reduction by single-electron transferring dehydrogenases-electrontransferases

Chlorination Disinfection By-Products in Drinking Water and Congenital Anomalies: Review and Meta-Analyses

This study aims to review epidemiologic evidence of the association between exposure to chlorination disinfection by-products (DBPs) and congenital anomalies. All epidemiologic studies that evaluated a relationship between an index of DBP exposure and risk of congenital anomalies were analyzed. For all congenital anomalies combined, the meta-analysis gave a statistically significant excess risk for high versus low exposure to water chlorination or TTHM (17%; 95% CI, 3-34) based on a small number of studies. The meta-analysis also suggested a statistically significant excess risk for ventricular septal defects (58%; 95% CI, 21-107), but based on only three studies, and there was little evidence of an exposure-response relationship. It was observed no statistically significant relationships in the other meta-analyses and little evidence for publication bias, except for urinary tract defects and cleft lip and palate. Although some individual studies have suggested an association between chlorination disinfection by-products and congenital anomalies, meta-analyses of all currently available studies demonstrate little evidence of such association

Applying an ecosystem services framework on nature and mental health to recreational blue space visits across 18 countries

The effects of ‘nature’ on mental health and subjective well-being have yet to be consistently integrated into ecosystem service models and frameworks. To address this gap, we used data on subjective mental well-being from an 18-country survey to test a conceptual model integrating mental health with ecosystem services, initially proposed by Bratman et al. We analysed a range of individual and contextual factors in the context of 14,998 recreational visits to blue spaces, outdoor environments which prominently feature water. Consistent with the conceptual model, subjective mental well-being outcomes were dependent upon on a complex interplay of environmental type and quality, visit characteristics, and individual factors. These results have implications for public health and environmental management, as they may help identify the bluespace locations, environmental features, and key activities, that are most likely to impact well-being, but also potentially affect recreational demand on fragile aquatic ecosystems

Associations between green/blue spaces and mental health across 18 countries

Living near, recreating in, and feeling psychologically connected to, the natural world are all associated with better mental health, but many exposure-related questions remain. Using data from an 18-country survey (n= 16,307) we explored associations between multiple measures of mental health (positive well-being, mental distress, depression/anxiety medication use) and: (a) exposures (residential/recreational visits) to diferent natural settings (green/inland-blue/coastalblue spaces); and (b) nature connectedness, across season and country. People who lived in greener/ coastal neighbourhoods reported higher positive well-being, but this association largely disappeared when recreational visits were controlled for. Frequency of recreational visits to green, inland-blue, and coastal-blue spaces in the last 4 weeks were all positively associated with positive well-being and negatively associated with mental distress. Associations with green space visits were relatively consistent across seasons and countries but associations with blue space visits showed greater heterogeneity. Nature connectedness was also positively associated with positive well-being and negatively associated with mental distress and was, along with green space visits, associated with a lower likelihood of using medication for depression. By contrast inland-blue space visits were associated with a greater likelihood of using anxiety medication. Results highlight the benefts of multi-exposure, multi-response, multi-country studies in exploring complexity in nature-health associations.info:eu-repo/semantics/publishedVersio

Research note: residential distance and recreational visits to coastal and inland blue spaces in eighteen countries

Varied categorisations of residential distance to bluespace in population health studies make comparisons difficult. Using survey data from eighteen countries, we modelled relationships between residential distance to blue spaces (coasts, lakes, and rivers), and self-reported recreational visits to these environments at least weekly, with penalised regression splines. We observed exponential declines in visit probability with increasing distance to all three environments and demonstrated the utility of derived categorisations. These categories may be broadly applicable in future research where the assumed underlying mechanism between residential distance to a blue space and a health outcome is direct recreational contact.info:eu-repo/semantics/publishedVersio

Environmental risk factors of pregnancy outcomes: A summary of recent meta-analyses of epidemiological studies.

Background Various epidemiological studies have suggested associations between environmental exposures and pregnancy outcomes. Some studies have tempted to combine information from various epidemiological studies using meta-analysis. We aimed to describe the methodologies used in these recent meta-analyses of environmental exposures and pregnancy outcomes. Furthermore, we aimed to report their main findings. Methods We conducted a bibliographic search with relevant search terms. We obtained and evaluated 16 recent meta-analyses. Results The number of studies included in each reported meta-analysis varied greatly, with the largest number of studies available for environmental tobacco smoke. Only a small number of the studies reported having followed meta-analysis guidelines or having used a quality rating system. Generally they tested for heterogeneity and publication bias. Publication bias did not occur frequently. The meta-analyses found statistically significant negative associations between environmental tobacco smoke and stillbirth, birth weight and any congenital anomalies; PM2.5 and preterm birth; outdoor air pollution and some congenital anomalies; indoor air pollution from solid fuel use and stillbirth and birth weight; polychlorinated biphenyls (PCB) exposure and birth weight; disinfection by-products in water and stillbirth, small for gestational age and some congenital anomalies; occupational exposure to pesticides and solvents and some congenital anomalies; and agent orange and some congenital anomalies. Conclusions The number of meta-analyses of environmental exposures and pregnancy outcomes is small and they vary in methodology. They reported statistically significant associations between environmental exposures such as environmental tobacco smoke, air pollution and chemicals and pregnancy outcomes

Perspectives on the Trypanosoma cruzi-host cell receptor interaction

Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions. Some of the key receptors considered are those for thromboxane, bradykinin, and for the nerve growth factor TrKA. Other important receptors such as galectin-3, thrombospondin, and laminin are also discussed. Investigation into the molecular biology and cell biology of host receptors for T. cruzi may provide novel therapeutic targets