[pt] No litoral brasileiro, do Rio Grande do Norte até Rio de Janeiro, se encontram os mais importantes depósitos de areias monazíticas No litoral do Município de São Francisco de Itabapoana, no estado de Rio de Janeiro, encontram-se importantes jazidas de areias monazíticas, e na vila de Buena, situada neste município, se encontra uma usina de beneficiamento de areias monazíticas. Nela são obtidos concentrados de ilmenita, zirconita, rutilo e monazita utilizando separadores letrostáticos, eletromagnéticos e gravimétricos (espirais, planos inclinados e mesas vivratorias). Com o objetivo de caracterizar a exposição dos habitantes desta vila a partículas de poeira na fração respirável foram coletadas amostras de aerossóis usando impactadores em cascata, amostradores portáteis com ciclone e amostras de bioindicadores. As amostras foram analisadas pelo método PIXE (Particle Induced X ray Emission) para determinação da concentração dos metais e do MMAD (Mass Median Aerodinamic Diameter), por PDMS (Plasma Desorption Mass Spectrometry) para identificação dos compostos presentes. As amostras de aerossóis coletadas com amostradores portáteis e de bioindicadores foram analisadas para determinação da concentração dos isótopos das séries naturais do tório e urânio. Os resultados indicam que os habitantes estão expostos a partículas contendo metais na fração respirável do aerossol geradas por fontes tanto antropogênicas , quanto naturais. As amostras de bioindicadores indicam os habitantes da vila tem estado expostos a radionuclídeos das séries naturais do tório e urânio nos últimos 15 anos. / [en] The main deposit of mineral sands in Brasil occur from the Rio Grande do Norte State to Rio de Janeiro State. The main commercial deposit is located in Buena, a village at São Francisco de Itabapoana, Rio de Janeiro State. In buena there is a plant that process minerals sands to obtain ilmenite, zirconite, rutile and monazite concentrates. This plant belongs to the Industrias Nucleares Brasileiras (INB). Close to this plant there is a small village. Aerosols samples were collected using cascade impactors and cyclones in order to characterize human exposure to airborne particles in the respirable fraction. Lichens samples were also collected. The samples were analyzed by PIXE (Particle Induced X ray Emission) for determination of elemental mass concentration and MMAD (Mass Median Aerodynamic Diameter). PDMS (Plasma Desorption Mass Spectrometry) allows the identification of the chemicals compounds present in the samples. The concentrations of radionuclides from the thorium and uranium natural series were also determined. The results show that the inhabitants were espoused to airborne particles in the respirable fraction of aerosols from natural and anthropogenic sources. The lichens samples indicate that the inhabitants have been exposed to radionuclides from the thorium and uranium natural series since last 15 years.

The primary aim was to validate and implement a urinary pharmacokinetic method for terbutaline to determine the relative lung and systemic bioavailability following inhalation and to measure the in-vitro characteristics of the emitted dose by these inhalation methods. Two new robust, accurate and sensitive high performance liquid chromatography methods for the determination of terbutaline in aqueous and urine samples were validated in accordance with the FDA and ICH guidelines. Terbutaline was extracted using solid phase extraction with salbutamol and bamethane as internal standards. The accuracy, precision, lower limit of detection and recovery for both methods were within recognized limits. The in-vitro characteristics of terbutaline sulphate inhalers were measured according to standard compendial methodology as well as adaptation of this methodology to simulate routine patient use. The dose emission of terbutaline sulphate from a Bricanyl Turbuhaler was determined using an inhalation volume of 4 L at inhalation flows of 10-60 L min-1. The particle size distribution was measured using an Anderson Cascade Impactor (ACI) with a mixing inlet valve to allow measurement at different flows. A steady increase in total emitted dose (TED) and the fine particle dose (FPD) was observed as the inhalation flow increased thereby highlighting the flow dependent dose emission characteristics of the Turbuhaler. The in-vitro dose emission characteristics of terbutaline sulphate from Bricanyl MDIs were measured according to the standard compendial methodology at a flow of 28.3 L min-1 using a 4 L inhalation volume. The TED and particle size distribution of terbutaline sulphate from the Bricanyl MDI were determined alone and with different spacers [AeroChamber Max (AMAX), AeroChamber Plus (APLUS), Fisonair and Nebuhaler]. The TED from the MDI alone was significantly higher than all MDI+spacers (p<0.001). The MDI with APLUS resulted in the smallest mass median aerodynamic diameter (MMAD) and the highest fine particle fraction (FPF). The MDI with AMAX resulted in the highest FPD. The in-vitro characteristics of terbutaline sulphate from Bricanyl respules using the Aeroneb Pro (vibrating mesh) and Sidestream jet nebulisers were determined by the CEN methodology and the Next Generation Impactor (NGI) methodology. The Aeroneb Pro was found to have significantly better aerodynamic properties than the Sidestream. The results from the NGI method were significantly different from the CEN method suggesting further evaluation of both methods. Cooling the NGI decreased the evaporation effect. Twelve healthy volunteers (6 females) completed in-vivo urinary terbutaline pharmacokinetic studies to determine the relative bioavailability following inhalation. The differences between the amounts excreted 0.5, 1, 2, 4, 6 and 24 hour post inhalation from a Bricanyl MDI (I) and oral (O) dosing of 500 µg terbutaline sulphate and with the co-administration of oral charcoal (IC and OC, respectively) were studied. No terbutaline was found in OC samples. The amount of terbutaline excreted 30 minutes post I and IC were significantly (p<0.001) higher than post O suggesting that the amount of terbutaline excreted 30 minutes post dosing can be used as an index of the lung deposition. The amount of terbutaline excreted 24 hour post I was significantly (p<0.01) higher than post O suggesting that the amount of terbutaline excreted 24 hour post dosing can be used as an index of the relative systemic bioavailability. The dose response relationships and the low inter and intra-subject variability studies confirm the feasibility of this method. To demonstrate the application of the method the effect of inhalation technique on the lung and systemic bioavailability following inhalation from a dry powder inhaler was evaluated. The effect of different spacers on the dose emitted from the Bricanyl MDI and the effect of different nebulisers on the dose emitted were also studied using twelve healthy volunteers (6 females) for each study. A fast inhalation flow using the Bricanyl Turbuhaler resulted in significantly higher amounts of terbutaline excreted 0.5 and 24 hour post dosing (2 doses of 500µg terbutaline sulphate from Bricanyl Turbuhaler) than slow inhalation flow (p<0.001). The Bricanyl MDI alone resulted in a significantly higher amount of terbutaline excreted 24 hour post dosing (2 doses of 250µg terbutaline sulphate from Bricanyl MDI) and significantly lower amounts excreted 30 minutes post dosing than the MDI+Spacers. The AMAX provided a greater amount of urinary terbutaline excreted 30 minutes post dosing than the APLUS and Nebuhaler. The Aeroneb Pro resulted in significantly higher amounts of terbutaline excreted 0.5 and 24 hour post dosing (1 dose of 5mg/2ml terbutaline sulphate from Bricanyl respule) than a Sidestream Jet nebuliser (p<0.001). Further application of the method was demonstrated by 12 (6 female) COPD non-invasive mechanically ventilated patients. One dose of 2mg in 0.8ml terbutaline sulphate respiratory solution from Aeroneb Pro and one dose of 5mg in 2ml terbutaline sulphate respiratory solution from Sidestream jet nebuliser resulted in a similar amounts of urinary terbutaline excreted 0.5 and 24 hour post dosing. The results were consistent with the results of the ex-vivo study performed on the same patients. The thesis highlights extension of the urinary pharmacokinetic method following inhalation to terbutaline and its application in volunteer and patient studies.

This thesis dissertation assessed workers who work in poultry barns and their occupational environment in relation to the type of bird housing in which they were exposed (cage-housed birds (CH) or floor-housed birds (FH)) and examined the environmental variables including dust and endotoxin and potential relationships to respiratory symptoms of workers. <p>A cross sectional study was undertaken to assess the environmental exposure levels and respiratory health effects of workers who worked in CH and FH poultry operations. The respiratory results suggested an asthma-like syndrome in these workers. Workers who worked in CH facilities reported greater current and chronic respiratory symptoms and significantly greater current and chronic phlegm as compared to workers from FH facilities. Workers from CH poultry facilities were exposed to greater endotoxin load than workers from FH facilities, but workers from FH operations were exposed to greater levels of total dust. It was found that endotoxin load (EU/mg) was a significant predictor of chronic phlegm for all poultry workers.<p>The effects on dust and endotoxin measurements when utilizing a Marple impactor with greased or ungreased impaction surfaces when sampling in an agricultural environment were unknown, and the potential for effects was tested. There were no significant differences in the aerosol mass median aerodynamic diameters between the greased and ungreased Marple impactors. Endotoxin analysis results appeared to be influenced by impaction grease particularly when very low amounts of endotoxin were present. <p>Size fractioning the dust and endotoxin using Marple impactors in CH and FH poultry operations showed that endotoxin load (EU/mg) was significantly higher in the respirable fraction of area samples in CH poultry operations as compared to FH operations. There were no differences in endotoxin load in the non-respirable size fractions for area samples between CH and FH operations. FH poultry operations had significantly greater dust mass and dust concentration in both respirable and non-respirable fractions for FH operations. There was significantly greater endotoxin load (EU/mg) in the 3.5-6.0 micron size fraction for the CH poultry operations as compared to the FH operations.

This thesis dissertation assessed workers who work in poultry barns and their occupational environment in relation to the type of bird housing in which they were exposed (cage-housed birds (CH) or floor-housed birds (FH)) and examined the environmental variables including dust and endotoxin and potential relationships to respiratory symptoms of workers. <p>A cross sectional study was undertaken to assess the environmental exposure levels and respiratory health effects of workers who worked in CH and FH poultry operations. The respiratory results suggested an asthma-like syndrome in these workers. Workers who worked in CH facilities reported greater current and chronic respiratory symptoms and significantly greater current and chronic phlegm as compared to workers from FH facilities. Workers from CH poultry facilities were exposed to greater endotoxin load than workers from FH facilities, but workers from FH operations were exposed to greater levels of total dust. It was found that endotoxin load (EU/mg) was a significant predictor of chronic phlegm for all poultry workers.<p>The effects on dust and endotoxin measurements when utilizing a Marple impactor with greased or ungreased impaction surfaces when sampling in an agricultural environment were unknown, and the potential for effects was tested. There were no significant differences in the aerosol mass median aerodynamic diameters between the greased and ungreased Marple impactors. Endotoxin analysis results appeared to be influenced by impaction grease particularly when very low amounts of endotoxin were present. <p>Size fractioning the dust and endotoxin using Marple impactors in CH and FH poultry operations showed that endotoxin load (EU/mg) was significantly higher in the respirable fraction of area samples in CH poultry operations as compared to FH operations. There were no differences in endotoxin load in the non-respirable size fractions for area samples between CH and FH operations. FH poultry operations had significantly greater dust mass and dust concentration in both respirable and non-respirable fractions for FH operations. There was significantly greater endotoxin load (EU/mg) in the 3.5-6.0 micron size fraction for the CH poultry operations as compared to the FH operations.

The primary aim was to validate and implement a urinary pharmacokinetic method for terbutaline to determine the relative lung and systemic bioavailability following inhalation and to measure the in-vitro characteristics of the emitted dose by these inhalation methods. Two new robust, accurate and sensitive high performance liquid chromatography methods for the determination of terbutaline in aqueous and urine samples were validated in accordance with the FDA and ICH guidelines. Terbutaline was extracted using solid phase extraction with salbutamol and bamethane as internal standards. The accuracy, precision, lower limit of detection and recovery for both methods were within recognized limits. The in-vitro characteristics of terbutaline sulphate inhalers were measured according to standard compendial methodology as well as adaptation of this methodology to simulate routine patient use. The dose emission of terbutaline sulphate from a Bricanyl Turbuhaler was determined using an inhalation volume of 4 L at inhalation flows of 10-60 L min-1. The particle size distribution was measured using an Anderson Cascade Impactor (ACI) with a mixing inlet valve to allow measurement at different flows. A steady increase in total emitted dose (TED) and the fine particle dose (FPD) was observed as the inhalation flow increased thereby highlighting the flow dependent dose emission characteristics of the Turbuhaler. The in-vitro dose emission characteristics of terbutaline sulphate from Bricanyl MDIs were measured according to the standard compendial methodology at a flow of 28.3 L min-1 using a 4 L inhalation volume. The TED and particle size distribution of terbutaline sulphate from the Bricanyl MDI were determined alone and with different spacers [AeroChamber Max (AMAX), AeroChamber Plus (APLUS), Fisonair and Nebuhaler]. The TED from the MDI alone was significantly higher than all MDI+spacers (p<0.001). The MDI with APLUS resulted in the smallest mass median aerodynamic diameter (MMAD) and the highest fine particle fraction (FPF). The MDI with AMAX resulted in the highest FPD. The in-vitro characteristics of terbutaline sulphate from Bricanyl respules using the Aeroneb Pro (vibrating mesh) and Sidestream jet nebulisers were determined by the CEN methodology and the Next Generation Impactor (NGI) methodology. The Aeroneb Pro was found to have significantly better aerodynamic properties than the Sidestream. The results from the NGI method were significantly different from the CEN method suggesting further evaluation of both methods. Cooling the NGI decreased the evaporation effect. Twelve healthy volunteers (6 females) completed in-vivo urinary terbutaline pharmacokinetic studies to determine the relative bioavailability following inhalation. The differences between the amounts excreted 0.5, 1, 2, 4, 6 and 24 hour post inhalation from a Bricanyl MDI (I) and oral (O) dosing of 500 µg terbutaline sulphate and with the co-administration of oral charcoal (IC and OC, respectively) were studied. No terbutaline was found in OC samples. The amount of terbutaline excreted 30 minutes post I and IC were significantly (p<0.001) higher than post O suggesting that the amount of terbutaline excreted 30 minutes post dosing can be used as an index of the lung deposition. The amount of terbutaline excreted 24 hour post I was significantly (p<0.01) higher than post O suggesting that the amount of terbutaline excreted 24 hour post dosing can be used as an index of the relative systemic bioavailability. The dose response relationships and the low inter and intra-subject variability studies confirm the feasibility of this method. To demonstrate the application of the method the effect of inhalation technique on the lung and systemic bioavailability following inhalation from a dry powder inhaler was evaluated. The effect of different spacers on the dose emitted from the Bricanyl MDI and the effect of different nebulisers on the dose emitted were also studied using twelve healthy volunteers (6 females) for each study. A fast inhalation flow using the Bricanyl Turbuhaler resulted in significantly higher amounts of terbutaline excreted 0.5 and 24 hour post dosing (2 doses of 500µg terbutaline sulphate from Bricanyl Turbuhaler) than slow inhalation flow (p<0.001). The Bricanyl MDI alone resulted in a significantly higher amount of terbutaline excreted 24 hour post dosing (2 doses of 250µg terbutaline sulphate from Bricanyl MDI) and significantly lower amounts excreted 30 minutes post dosing than the MDI+Spacers. The AMAX provided a greater amount of urinary terbutaline excreted 30 minutes post dosing than the APLUS and Nebuhaler. The Aeroneb Pro resulted in significantly higher amounts of terbutaline excreted 0.5 and 24 hour post dosing (1 dose of 5mg/2ml terbutaline sulphate from Bricanyl respule) than a Sidestream Jet nebuliser (p<0.001). Further application of the method was demonstrated by 12 (6 female) COPD non-invasive mechanically ventilated patients. One dose of 2mg in 0.8ml terbutaline sulphate respiratory solution from Aeroneb Pro and one dose of 5mg in 2ml terbutaline sulphate respiratory solution from Sidestream jet nebuliser resulted in a similar amounts of urinary terbutaline excreted 0.5 and 24 hour post dosing. The results were consistent with the results of the ex-vivo study performed on the same patients. The thesis highlights extension of the urinary pharmacokinetic method following inhalation to terbutaline and its application in volunteer and patient studies. / Egyptian Culture Office in UK, Missions Department in Egypt