Aggressive penetration of nanomaterials in different spheres of our life from novel technologies to a plethora of consumer products, raises concerns about their possible adverse effects on public health. Several studies report that nanotubes cause lung toxicity. With increase in day-to-day applications of carbon nanotubes, particulate exposure either under occupational or environmental settings is inevitable. In the classic inflammatory response to nanotubes, emigration of neutrophils (PMNs) followed by macrophages into sites of particle deposition has been observed. The major role of the cells is to phagocytoze and promotes particulate clearance and the clearance might be essentially dependent on effective recognition. Carbon nanotubes are not effectively recognized by professional phagocytes and delayed clearance of particles within the lung parenchyma can thus be majorly attributed to impaired phagocytosis or deficiency in components involving their effective degradation. We in our research coated nanotubes with biomolecules to promote recognition, uptake and biodegradation by professional phagocytes. Coating nanotubes with eat-me-phospholipid signal, phosphatidylserine proved to be an effective strategy for targeting particles to professional phagocytes, specifically macrophages both in vitro and in vivo. However, opsonization of nanotubes made them competent for both macrophages and neutrophils. This targeting also enhanced the biodegradation in neutrophils and to a lesser extent in macrophages via action of myeloperoxidase and its potent oxidants whose critical role in biodegradation was delineated in cell free based in vitro studies. Further, in vivo experiments using wild type and myeloperoxidase null mice showed a significantly lower degree of biodegradation and particle elimination in latter animal type, underscoring the role of neutrophil peroxidase in biodegrading carbon nanotubes. Using contemporary techniques- confocal, transmission and scanning electron microscopy, Vis-NIR and Raman spectroscopy, we evaluated the hypothesis. Taken together, the results from the doctoral work suggest that targeting of nanotubes to professional phagocytes can be achieved by coating with certain biomolecules and this targeting can reduce the biopersistence and inflammation associated due to the presence of otherwise relatively biodurable nanotubes in biological ambience. The dissertation also foresees functionalization of nanotubes as a strategy to combat potential toxic effects of nanotubes which pose potential risk to the public health.

The Greater Pittsburgh Area is famous for its three rivers: the Allegheny, Monongahela, and Ohio Rivers. These rivers have a history of being polluted by decades of mine runoff and chemicals released by industrial sites. New problems, such as pollution from endocrine disrupting compounds and xenoestrogens, have recently been discovered in this well known aquatic environment and are suspected to be caused by the failing sewer system. Personal care products, pharmaceuticals and plasticizers all have the potential to enter the water supply though both treated and untreated sewage. Many of these compounds are known or suspected endocrine disruptors. Estrogenic potential of fish extracts from flesh/fat tissue captured from Freeport and Ford City was studied via the E-Screen Assay on MCF-7, T47D and BT-20 human breast cancer cell lines. Results showed weak estrogenic responses in both MCF-7 and T47D cell lines, with no significant differences for fish gender, weight, or sample location. Estrogenic potential of extracts from fish brain tissue was tested via Bromodeoxyuridine MCF-7 Analysis and paired with High Performance Liquid Chromatography-Mass Spectrometry to investigate the presence of specific xenoestrogens in the fish extracts. Fifty eight fish were sampled from rivers in the Greater Pittsburgh Area. All samples were non-detectable for methyl, ethyl, propyl and butyl parabens. Bisphenol A (BPA) was detected in 44 of the 58 samples, with a range from non-detectable to 120 pg/gram. The Harmarville sample location had higher results for all analyses when compared to all other sample sites. In summary, this dissertation supported all previous available literature leading to the conclusion that parabens are safe to remain on the market and are not a significant environmental concern. In particular, there does not seem to be any need for concern over paraben levels detected in the Greater Pittsburgh Area river system and water supply. The BPA portion of this research was in agreement with previous literature as to its bioconcentration tendencies; however, new implications regarding the public health significance of the effects from BPA in brain tissue may require some re-evaluation of concerns about BPA transport and fate in the environment around Pittsburgh and elsewhere.

Mitochondrial dysfunction, particularly in relation to electron transport chain (ETC) derived oxidative stress, is widely held to be important in numerous pathologies. However, mitochondrial levels of the bioenergetically critical small inorganic molecules are still debatable or unknown. Nevertheless, investigation of the behavior of the ETC components, individually and collectively, in response to varying the levels of these species is still of considerable importance. This dissertation investigated the reaction of the reduced forms of isolated bovine complex III, cytochrome c and complex IV with peroxynitrite in the presence and absence of CO2. The presence of CO2 significantly modulates the mechanisms and extent of the cofactor oxidations. The characteristics of peroxynitrite-modified ferricytochrome c, prepared in the presence and absence of CO2, was examined by a variety of spectroscopic methods. In the absence of CO2, oxidation of the methionine 80 axial heme ligand to methionine sulfoxide results. During complex IV turnover by native ferrocytochrome c at low ionic strength increased rates were observed when the peroxynitrite modified cytochrome c is added - indicating preferential binding of the modified cytochrome to a high affinity/low activity electron-entry site on the enzyme, directing native ferrocytochrome c to bind to a lower affinity/higher activity site. It is unclear that formation of small quantities of either peroxynitrite-modified cytochrome c is proapoptotic. Since the limiting reagent in the reaction of superoxide with nitric oxide is peroxynitrite, the amount of superoxide formed biologically is critical information. The commonly employed molecular probes for superoxide, hydroethidine, and its mitochondrially-targeted derivative, MitoSoxTM, were shown to undergo reactions with components of the mitochondrial ETC including reduction of complex IV and partial reduction of complex III. The reaction with complex IV accounts for an oxygen (and hence superoxide), independent fluorescent response of MitoSox™ in cultured endothelial cells. However, the cationic ethidium species formed during oxidation of the probes by the ETC enzymes inhibit the normal turnover of complex IV by blocking transfer of electrons from ferrocytochrome c to the oxidase. In the case of oxidized MitoSox™, the observed inhibition under typical assay conditions was substantial at inhibitor levels comparable to the concentration of substrate cytochrome c. Therefore, this work has special public health relevance since it not only reviews the possible mechanisms for oxidative stress in mitochondria but also reassesses the use of MitoSox™ as it is a net generator of superoxide.

Aflatoxin, produced by the fungi Aspergillus flavus and A. parasiticus, is the most potent naturally occurring human hepatocarcinogen. Food crops colonized by these fungi, especially maize and groundnut, are the major sources of dietary aflatoxin exposure. Aflatoxin and chronic hepatitis B virus (HBV) infection, two liver cancer risk factors that synergize with each other, are prominent in sub-Saharan Africa and certain parts of Asia. Furthermore, increasing evidence from epidemiological studies suggests that aflatoxin may cause child growth impairment, which can increase risks of premature deaths. A broad range of aflatoxin control strategies, developed to reduce aflatoxin exposure or its toxicity, include preharvest, postharvest, and dietary interventions; as well as the HBV vaccine, which does not reduce aflatoxin exposure but reduces the risk of aflatoxin-induced liver cancer. We compared the efficacy and the cost-effectiveness of four aflatoxin risk-reduction strategies: HBV vaccine, biocontrol (preharvest), a postharvest intervention package, and NovaSil clay (dietary) in preventing liver cancer and stunting in Nigeria. Aflatoxin and chronic HBV infection are attributable for 8-27%, and 59-62%, respectively, of total liver cancers in Nigeria. We found that the HBV vaccine provides the greatest health-based efficacy and the lowest cost to avert one disability-adjusted life year (DALY) in Nigeria, compared with the selected aflatoxin control interventions. The prospective burden of aflatoxin-related stunting in Nigeria varies depending on aflatoxin exposure levels, which can vary substantially by year and location. At higher levels of aflatoxin exposure, the burden of aflatoxin-associated stunting is significant. Preventing stunting by any of these interventions would greatly reduce the cost per DALY and turn these interventions from non-cost-effective to very cost-effective. Our technical feasibility assessments of these four interventions suggest some advantages and disadvantages of each intervention over the others. These data are crucial components in a decision making process to effectively allocate public health resources, and to position interventions for further development of public health interventions to prevent some aflatoxin-related public health problems, especially in high risk populations.

This study examines three process measures of diabetic care and their association with four complications of diabetes - Coronary Artery Disease (CAD), Heart Failure (HF), Stroke and Renal Disease (RD) - in a cohort comprised of hourly and salaried employees of a single large manufacturing company at geographically diverse regions in the United States. Quality of care was measured by adherence to consensus standards for A1C and lipid testing and screening for microalbuminuria. A retrospective cohort study was conducted from January 1, 2003 to December 31, 2009 of 1,797 diabetic employees of a US manufacturer who were enrolled in the same health insurance plan. Diabetics who received all three QOCM in the baseline year were compared to diabetics who received less than three QOCM in the baseline year and were analyzed to address their association with the four complications. Cox proportional hazard regression models were used to assess potential associations between diabetes QOCM and time to complication. Potential confounding risk factors included sex, age, ethnicity, income, marital status, education, smoking, diabetes severity and health comorbidity risk scores. The overall health benefits for diabetics who received all three QOCM at baseline were noteworthy; they experienced reduced risk for HF (HR 0.39, CI [.19 - .81], p = 0.0117) and RD (HR 0.48, CI [.24 - .95] p = 0.0339) compared to the people who received less than three QOCM. Results suggest that diabetics who received all three QOCM experienced lower complications and is associated with reduced complication risk - regardless of access to care and other factors. These results suggest that any improvement in screening is likely to reduce the risk of diabetes complications. This study contributes to the literature by examining adherence to recommended processes of care and patient complications together. The public health implications of this study can be used to inform the design or revision of disease management programs and process of care measures.

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Occupational health surveillance programs are designed to evaluate and reduce injury, illness, and deaths related to workplace hazards. In the state of Florida, there are numerous industries where workers are potentially exposed to airborne hazards from gases, vapors and dusts. Airborne occupational exposures to irritants, vesicants, and fibrogens have the potential to cause pulmonary function impairment if exposures are not properly controlled for high-level acute exposure as well as chronic exposure. For occupations that demand workers be exposed to substances known to be associated with pulmonary function impairment, respirators may be a principal method for exposure control. OSHA requires pulmonary function testing for specific substances and it is a best practice that is utilized in a majority of occupational settings and is typically included in an organizations respiratory protection program. A literature review identified that boat manufacturing, utilities, and first responders in the State of Florida have the potential for increased pulmonary impairment amongst workers. This research demonstrated the feasibility of using pulmonary function data collected for the purposes of compliance and/or best practices for workers who use respiratory protection because they are potentially exposed to pulmonary toxicants in the workplace. This research did not identify any pulmonary function deficits in the target occupational populations and it demonstrated that in most cases, the study populations had modestly superior pulmonary function compared to a baseline population.

Diss. (sammanfattning) Uppsala : Univ., 2001. / Härtill 4 uppsatser.

Thesis (M.P.H.)--University of Michigan, 1944.

Thesis (M.S.P.H.)--University of Michigan, 1939.