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Record Count: 6
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header (Title, Principal Investigator, Institution, City, ST, Award Code, or
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DESCRIPTION (provided by applicant): Malaria transmission is one of the most important environmental and occupational hazards faced by impoverished African populations today. Malaria transmission intensity is predominantly dependent on environmental factors because mosquitoes and humans ultimately rely on the same fundamental resources: land and water. The impact of natural resource utilization choices on malaria risk and health equity is poorly understood but malaria prevalence and incidence reductions of 30% or more have been achieved through agricultural development strategies which optimize economic, societal and health service development. A number of participatory approaches are emerging which might facilitate the development and dissemination of innovative environmental management interventions: land use planning, farmer field schools, producers' cooperatives or associations, and fair trading initiatives. The Kilombero Valley in Southern Tanzania is an ideal setting for developing district-based schemes for participatory natural resource management that can be scaled up to mitigate health inequities throughout Tanzania and elsewhere in Africa. Kilombero has diverse ecology, demography and natural resource utilization patterns, driven by the seasonal inundation of its extensive wetlands. The fringes of the inundation zone constitute a focus for conflict over shared resources between farmers and pastoralists where malaria transmission is seasonally intense and highly heterogeneous. Conflicts, inequities and risks arising from this complex mosaic of interactions of humans with their environment have been prioritized for mitigation by the residents, local government, national government and supporting research institutions. Local government in Kilombero is piloting farmer field schools, farmers' associations and participatory land-use planning to address these problems. We propose to develop a model district-level platform that enables ethnically diverse communities to participate fully in managing their own natural resources and environmental health, focusing particularly on malaria. Our long- term goal is to mitigate health inequities that arise from ongoing pressures, conflicts, limitations and inequities arising from use of land and water in Africa. Farmer-pastoralist conflicts are common all across tropical Africa so the results of this project will be useful to many other African countries and communities faced with similar challenges.
DESCRIPTION (provided by applicant)
Global environmental health concerns can only be addressed through the cooperative actions of multiple countries and institutions, but this requires effective leadership and coordination. The International Programme on Chemical Safety (IPCS) was established in 1980 as the lead international coordinating body to provide science-based assessments of the potential health risks posed by environmental contaminants. IPCS is managed by the World Health Organization (WHO) but involves many other United Nations, regional, international, national, and non-governmental organizations. IPCS accomplishes most of its work through the efforts of a broad diverse network of internationally recognized scientific experts. The National Institute of Health (NIH)/National Institute of Environmental Health Sciences (NIEHS) played a key role in the formation of IPCS, and NIEHS (intramural and extramural) continues to play a significant leadership role for many IPCS activities. A WHO/IPCS Interregional Research Unit (IRRU) is located on the NIEHS campus to implement the activities supported by the NIEHS-WHO Cooperative Agreement, which addresses the following global cross-cutting environmental health issues: 1) children's health and the environment; 2) toxicogenomics/gene-environment interactions/biomarkers; 3) persistent toxic substances and endocrine disruptors; 4) improved risk assessment methodologies; and 5) development of an integrated risk assessment approach with an emphasis on mixtures. A prototype, step-wise implementation strategy, shown to work very effectively has been developed to implement these aims. This strategy combines a regional approach with a flexible, modular process that allows for uncertainties of unforeseen scientific opportunities, generates unique scientific knowledge, and ultimately leads to the collaboration of research among scientists in developing and developed countries. In addition, this strategy has served as a catalyst for additional multi-partner support and collaborative actions. The activities supported by the Cooperative Agreement result in numerous publications, training of scientists and health care professionals, collaborative research opportunities, generation of unique scientific information and initiation of data collection archives, education, awareness raising, and information dissemination. Countries use these products to put in place evidence based public health, prevention, and remediation policies at the national and regional level.
DESCRIPTION (provided by applicant): The precise mechanism by which LH accelerates the transport of the substrate cholesterol from the cytosol to the inner mitochondrial membrane, the rate-determining step in steroidogenesis, is unknown. The mitochondrial high affinity cholesterol binding protein peripheral-type benzodiazepine receptor (PBR) and the hormone-induced cytosolic steroidogenic acute regulatory protein (StAR) were found to function in a coordinated manner to transfer cholesterol into mitochondria. We recently demonstrated that in Leydig cells the StAR-induced cholesterol import into mitochondria is mediated by PBR. Based on these findings we hypothesize that changes in the structure and levels of PBR determine the amount of StAR-mobilized cholesterol available for testosterone synthesis. We will test this hypothesis with 3 Specific Aims. In Aim 1, we will determine how changes in PBR structure affect cholesterol transport. Using biophysical techniques coupled with studies of in vitro reconstituted wild-type and mutant PBR, we will investigate the sequence of molecular events involved in the transfer of cholesterol mobilized by StAR to the cytochrome P450scc via PBR. In Aim 2, we will investigate the impact of PBR and StAR inactivation on cholesterol transport and steroidogenesis. PBR and StAR structure-based drug design identified lead compounds that target the cholesterol-binding domains of these proteins and inhibit steroidogenesis. The specificity of these in vitro effects and the in vivo effect of these compounds on steroid synthesis will be investigated. In Aim 3, we will test the hypothesis that the steroidogenic potential of Leydig cells is dictated by PBR protein levels, which in turn, are primarily regulated by PBR gene transcription. In search of molecules inhibiting PBR gene expression and steroidogenesis, we identified peroxisome proliferators (PPs), environmental agents known to exert testis-specific toxic effects. In vitro gene transcription and in vivo studies using transgenic mice showing restricted Leydig cell expression of the PBR gene promoter will be used to understand PBR expression and steroidogenesis in normal testes and testes exposed to the toxic effects of PPs. These studies should provide detailed understanding of the role of PBR and PBR-StAR interaction in cholesterol transport and steroidogenesis, and lead to better understanding of how environmental toxicants might function to elicit male reproductive pathologies as well as to therapies for such pathologies.
DESCRIPTION (provided by applicant): Particulate matter (PM2.5) has been linked to a range of serious respiratory and cardiovascular health problems. The nitroPAHs found in the (PM2.5) are formed during combustion processes or by either chemical or photochemical reactions of polycyclic aromatic hydrocarbon in polluted atmospheres. NitroPAHs have been identified in extracts of respirable particles collected from polluted urban air, diesel exhaust particles, automobile exhaust, coal fly ash and wood smoke. The nitroPAHs are typically less abundant in ambient air than PAHs and are found at concentrations in the range of pg/m3 to ng/m3. Nonetheless, some of them could be more mutagenic or carcinogenic in laboratory bioassays than the parent PAH. Thus, it is of great significance to understand their sources and transformations in the atmosphere in assessing environmental exposure and risks. Specifically, their transformations at the solid/air interface or in the liquid-like environment of the organic fraction of the combustion derived aerosols can have a significant impact on controlling their residence time in the environment. It is important to study the photochemistry in these two environments because their photodegradation can proceed by entirely different mechanisms depending on the reaction medium.
We are proposing to utilize techniques, already developed in our laboratory, to study the photochemical transformation mechanisms of nitroPAHs adsorbed or absorbed into models of atmospheric particulate matter in order to provide some understanding of the fate of these contaminants in the atmosphere. As we have found with PAHs, that phototransformations at the solid/air interface can have a significant impact in controlling their residence time in the environment, and are thus important in the evaluation of the potential risks of these contaminants, as well as in the possible design of systems for their removal. The working hypothesis is that the physical and chemical properties of the particulate matter are determining factors in the reactivity of the excited states and intermediates participating in the photochemical transformations of these pollutants in that environment. In order to understand the phototransformation mechanism of adsorbed or absorbed nitroPAHs we will: (1) isolate/and characterize the principal stable photoproducts and determine their quantum yields and the effect of the nature of the solvent (polar, non polar, polar aprotic, hydrogen abstraction easiness), and of organic compounds found in the atmospheric aerosols on the product yields, (2) isolate and characterize the principal stable photoproducts produced on adsorbents that mimic the atmospheric particle matter such as inorganic oxides, and sulfate salts, and determine the effect of the physical and chemical properties of the surfaces of these solids (such as composition average pore diameter, surface coverage) on the products relative yields, and to compare their relative yields and distribution with those obtained in the different solvents. The effect of coadsorbed water and oxygen on the yields will also be examined and (3) identify and characterize the participating excited states and reactive intermediates in the phototransformation process occurring in solution and on the surfaces. Related to this aim is the determination of the effect of organic cosolutes encountered in the atmospheric aerosol on the reaction kinetics of the intermediates. The physical properties of the participating excited states and reactive intermediates will be supported by quantum mechanical calculations.
DESCRIPTION (provided by applicant): The main objective of this research is to evaluate exposures associated with allergy, asthma and lung function among nurses. The research will involve analysis of data from the European Community Respiratory Health Survey (ECRHS), a follow-up study of a general population sample of approximately 7000 young adults in Europe, Australia and the US. The first specific aim is to evaluate workplace exposure to respiratory irritants and sensitizers among professional nurses employed in a range of industries and medical settings, including hospitals, clinics, and private health care offices. The second specific aim is to assess whether such exposures contribute to the incidence of respiratory symptoms and lung function decline. Analyses will examine the frequency and severity of new onset asthma and allergy symptoms, exacerbation of symptoms in previously symptomatic individuals, sensitization of previously asymptomatic individuals, and behavioral consequences of the frequent and/or severe symptoms. In addition, this research will also engage the postdoctoral fellow in other asthma studies within the ECRHS, including assessing potential occupational exposures in other non industrial workplaces, such as office buildings and schools, and assessing gene-environment interactions.
Crisp Terms/Key Words: postdoctoral investigator, environmental exposure, clinical research, gene environment interaction, human data, lung, respiratory function, respiratory disorder epidemiology, pollution related respiratory disorder, health survey, longitudinal human study, occupational disease /disorder, nurse, asthma, human subject, irritation /irritant, disinfectant
DESCRIPTION (provided by applicant): The main objective of this research is to evaluate exposures associated with allergy, asthma and lung function among nurses. The research will involve analysis of data from the European Community Respiratory Health Survey (ECRHS), a follow-up study of a general population sample of approximately 7000 young adults in Europe, Australia and the US. The first specific aim is to evaluate workplace exposure to respiratory irritants and sensitizers among professional nurses employed in a range of industries and medical settings, including hospitals, clinics, and private health care offices. The second specific aim is to assess whether such exposures contribute to the incidence of respiratory symptoms and lung function decline. Analyses will examine the frequency and severity of new onset asthma and allergy symptoms, exacerbation of symptoms in previously symptomatic individuals, sensitization of previously asymptomatic individuals, and behavioral consequences of the frequent and/or severe symptoms. In addition, this research will also engage the postdoctoral fellow in other asthma studies within the ECRHS, including assessing potential occupational exposures in other non industrial workplaces, such as office buildings and schools, and assessing gene-environment interactions.
Crisp Terms/Key Words: postdoctoral investigator, environmental exposure, clinical research, gene environment interaction, human data, lung, respiratory function, respiratory disorder epidemiology, pollution related respiratory disorder, health survey, longitudinal human study, occupational disease /disorder, nurse, asthma, human subject, irritation /irritant, disinfectant
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