Thesis (M.S.)--University of Michigan, 1981.

Thesis (M.S.)--University of Toledo, 2006. / "In partial fulfillment of the requirements for the degree of Master of Science in Occupational Health." Major advisor: Sheryl Milz. Includes abstract. Document formatted into pages: iv, 66 p. Title from title page of PDF document. Title at ETD Web site: Advantages of using the ANSI/ASHRAE 110-1995 tracer gas test method versus the ANSI/AIHA Z9.5-1992 face velocity test method for chemical laboratory hood certification. Bibliography: pages 58-61.

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 88-97).

In asthma therapy, the use of theophylline to prevent bronchial spasm and glucocorticoids to decrease inflammation is widely indicated. Apart from the acute asthma attack oral theophylline is treated for chronic therapy in order to minimize inflammation and to enhance the efficiency of corticosteroids and recover steroids’ anti-inflammatory actions in COPD treatment. The preferred application route for respiratory disease treatment is by inhalation, such as dry powder inhalers (DPI) being the delivery systems of first choice. As shown recently, there is an advantageous effect if the drugs are given simultaneously which is caused by a synergistic effect at the same target cell in the lung epithelia. Therefore, it seems rational to combine both substances in one particle. This type of particle has the advantage over a combination product containing both drugs in a physical mixture which occurs rather randomly deposition leading to API segregation and non-dose-uniformity. Dry powder inhalers (DPIs) is a type of therapeutic pharmaceutical formulations usually present in the solid form. Due to the nature of the solid-state, an understanding of chemical and physical properties must be established for acquiring optimum performance of the active pharmaceutical ingredients (APIs). In recent year, generation of DPIs is a destructive procedure to meet the micron size. Such processes are inefficient and difficult to control. Moreover, according to current researches on combination APIs formulation, this type of DPIs performed a greater variability in does delivery of each active, leading to poor bioavailability and limit clinical efficient. This result suggest that combination formulations require advanced quality and functionality of particles with suitable physicochemical properties. Hence, in order to production of binary and combination DPIs products, the aim of this study was to develop the spray drying and ultrasonic process for engineering of combination drug particles that will be delivered more efficiently and independently of dose variations to the lung. Microparticles were produced by spray drying or/and ultrasonic technique. The processing parameters and addition of excipients (polymers) were optimized using a full factorial design such that microparticles were produced in a narrow size range suitable for inhalation. Employing excipients resulted in high saturation environment leading to minimized sphere particles when compared to conventional solvent. Solid state characterization of microparticles using powder x-ray diffraction and differential scanning calorimetry indicated that the particles contained crystalline but no cocrystal. The combination particles comparable to or better than micronized drug when formulated as a powder blended with lactose. It was concluded that the use of HPMC enhanced crystallinity suitable for inhalation; and combination particles improved uniform distribution on the stage of NGI.

Orientador: Paulo Sergio Patto dos Santos / Banca: Valéria Nobre Leal de Souza Oliva / Banca: Carlos Augusto Araújo Valadão / Resumo: Foram analisados os efeitos cardiorrespiratórios e as variações do índice biespectral após a administração da infusão contínua de lidocaína em bezerros anestesiados com isofluorano sob ventilação controlada. Oito bezerros receberam infusão contínua de lidocaína (GL) ou salina 0,9% (GC). Após MPA com xilazina 0,05 mg/kg/IV e indução anestésica com quetamina 2mg/kg associada com midazolam o,1mg/kg, com os bezerros em decúbito lateral procedeu-se a intubação e administrou-se isofluorano 1,3%. Subsequentemente institui-se a VPPI com PPI de 15 cmH2O e fR de 6mpm. Decorridos 40 minutos sob anestesia com isofluorano com ventilação mecânica, aplicou-se lidocaína 2mg/kg e iniciou-se infusão contínua na taxa de 100 µg/kg/minuto (GL). Anotaram-se as variações da FC, PA, fR, SpO2, BIS e TR antes da MPA (MB) e 15 minutos após a MBA (MX) antes da administração da lidocaína (M0) e em intervalos de 20 minutos após o início da infusão dos fármacos (M20, M40, M60 e M80). As demais variáveis foram mensuradas a partir de M0. Após o final da infusão e desconexão, foram avaliados o período de tempo para a adoção de decúbito esternal e posição quadrupedal. Também foi mensurada a concentração sérica da lidocaína. A infusão continua de lidocaína não alterou as variáveis ventilométricas, hemogasométricas, índice biespectral e recuperação, porém diminuiu FC e IC. Conclui-se que apesar de ter causado redução da atividade cardíaca, a infusão contínua de lidocaína pode ser empregada como técnica anestésica em bezerros / Abstract: Cardiorespiratory effects and bispectral index were analised after continuous rate infusion of lidocaine in calves isoflurane-anesthetized under controlled ventilation. Eight calves received continuous rate infusion of lidocaine (LG) or saline 0.9% (CG). After premedication with xylazine 0.05 mg kg -1 IV and induction of anesthesia with ketamine 2 mg kg -1 associated with the midazolam, 1 mg kg -1 , with the calves in lateral recumbence preceded the intubation and was administered isoflurane 1.3%. IPPV was instituted with PIP of 15 cmH2O and RR of 6 beats min -1 . After 40 minutes with isoflurane anesthesia and mechanical ventilation was applied lidocaine 2 mg kg -1 and continuous rate infusion was started at a rate of 100 mg kg -1 min -1 (LG). Were recorded variations in HR, AP, fR, SPO2, BIS and RT before administration of premedication (MB) and 15 minutes after administration (MX) before administering lidocaine (M0) and every twenty minutes after the start of the infusion of drugs (M20, M40 M60 and M80).The other variables were measured from M0. After the end of infusion and disconnection, were evaluated the time to adopt sternal recumbency and standing position. Also measured the serum concentration of lidocaine. Continuous rate infusion of lidocaine did not change the ventilometry, blood gas, bispectral index and recovery, but decreased HR and CI. We conclude that although there was a reduction in cardiac activity, the continuous infusion of lidocaine may be used as anesthesia in calves / Mestre

Made available in DSpace on 2014-06-11T19:23:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-09-12Bitstream added on 2014-06-13T20:28:05Z : No. of bitstreams: 1 sa_pa_me_botfmvz.pdf: 312992 bytes, checksum: b7e2461b0b5749453a7647e0f5532c22 (MD5) / Em eqüinos, mudanças de decúbito durante anestesias prolongadas podem contribuir para a redução da oxigenação sanguínea; uma vez que o lobo pulmonar não dependente (funcional) é repentinamente comprimido. Hipotetizou-se que a mudança de decúbito durante a anestesia reduziria significativamente a oxigenação sanguínea (PaO2) e que a instituição da ventilação controlada seria capaz de prevenir a diminuição da PaO2 após a mudança de decúbito. Foram utilizados 16 eqüinos adultos hígidos, sem raça definida, com peso corpóreo de 444,3 ± 42,5 Kg, provenientes do Regimento de Cavalaria “Dragões da Independência”. Os animais foram submetidos a procedimentos cirúrgicos onde fosse necessária a mudança de decúbito. Mediante jejum alimentar de 12 horas e hídrico de 4 horas, os animais foram premedicados com acepromazina (0,05 mg/kg, IM) e após 30 minutos, com xilazina (0,5 mg/kg, IV). A anestesia foi induzida com diazepam (0,1 mg/kg, IV) e cetamina (2,2 mg/kg, IV) e mantida com halotano diluído em O2. A dobutamina foi empregada para manter a pressão arterial média acima de 70 mm Hg durante todo o procedimento. Os animais foram equitativamente divididos em 2 grupos, sendo que no grupo VE a anestesia foi mantida sob ventilação espontânea, enquanto no grupo VC a anestesia foi mantida sob ventilação controlada (frequência respiratória: 6 mov/min, relação inspiração/expiração: 1/3, volume corrente: 15 mL/kg e pressão de pico inspiratório entre 25 a 30 cm H2O). Os procedimentos cirúrgicos foram iniciados em decúbito lateral esquerdo (DLE) e, após 75 minutos, os animais foram reposicionados em decúbito lateral direito (DLD) até o término da cirurgia. Análises hemogasométricas do sangue arterial foram realizadas após 30 e 75 minutos de posicionamento em cada decúbito (M1 e M2 no DLE e M3 e M4 no DLD, respectivamente). Durante a VE, observou-se... / In horses, changes in body position during anesthesia may contribute to a reduction in arterial oxygenation because the non-dependent lung (functional) is suddenly compressed. It was hypothesized that the change in recumbency during anesthesia would significantly reduce the arterial oxygenation (PaO2) and the institution of controlled ventilation would prevent the descrease in PaO2 after the change in body position. A total of 16 healthy adult mixed breed horses horses of the Cavalry Regiment “Dragões da Independência”, weighting 444,3 ± 42,5 Kg, were used. All animals underwent procedures in which a change in body position would be necessary to perform surgery. Food and water were withheld for 12 and 4 hours respectively. All animals received acepromazine (0.05 mg/kg, IM), followed 30 minutes later by xylazine (0.5 mg/kg, IV). Anesthesia was induced with diazepam (0.1 mg/kg, IV) and ketamine (2.2 mg/kg, IV) and maintained with halothane in oxygen. Dobutamine was used to maintain mean arterial blood pressure above 70 mmHg throughout the procedure. The animals were equally divided into 2 groups: in the SV group anesthesia was maintaned under spontaneous ventilation whereas in the CV group anesthesia was maintained under controlled ventilation (respiratory rate: 6 breaths/min, inspiration-to-expiration ratio: 1/3, tidal volume: 15 ml/kg, and peak inspiratory pressure between 20 and 30 cmH2O). All surgical procedures were commenced in left lateral recumbency (LLR) and 75 minutes later the animals were repositioned in right lateral recumbency (RLR). Arterial blood gas analysis was performed at 30 and 75 minutes after the animals were placed in left recumbency (M1 and M2, respectively), and at 30 and 75 minutes after the animals were repositioned in right lateral recumbency (M3 and M4, respectively). Hypercapnia (PaCO2 > 45 mm Hg) and respiratory acidosis (pH < 7.35)... (Complete abstract click electronic access below)

Made available in DSpace on 2014-06-11T19:30:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-12-24Bitstream added on 2014-06-13T19:25:38Z : No. of bitstreams: 1 floriano_bp_me_araca.pdf: 900216 bytes, checksum: 5e9055fdcd50dd5a0e5c2ee686686c68 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Objetivou-se com este estudo avaliar os efeitos do isofluorano e tempo de anestesia com o mesmo sobre a perfusão tecidual de cães sob duas diferentes concentrações. Oito cães da raça Beagle foram anestesiados em múltiplos de CAM correspondentes a 1,5 (G1,5) e 2,0 (G2,0) CAM por duas horas, sendo mensuradas a cada 20 minutos as variáveis frequência cardíaca (FC), pressão sistólica (PAS), média (PAM) e diastólica (PAD), pressão da artéria pulmonar média (PAPm), pressão capilar pulmonar média (PCPm), pressão venosa central (PVC), índice cardíaco (IC), índice sistólico (IS), índice de trabalho ventricular esquerdo (ITVE), índice de resistência periférica total (IRPT), índice de resistência vascular pulmonar (IRVP), índice de oferta de oxigênio (IDO2), índice de consumo de oxigênio (IVO2), taxa de extração de oxigênio (TeO2), saturação venosa mista de oxigênio (SvO2) e lactato sanguíneo arterial. As médias de PAM, IC, IS e ITVE, diferiram significativamente entre os grupos, o que não foi observado nas variáveis IRPT e IRVP, as quais apresentaram diferença somente entre momentos de um mesmo grupo. Da mesma forma, houve diminuição progressiva da IRPT em G1,5, mas não em G2,0. Houve redução de IDO2 em G2,0 quando comparada a G1,5, mas não de IVO2. O lactato apresentou valores acima dos limites de referência, não diferindo entre grupos e reduzindo-se ao longo do tempo, enquanto que SvO2 foi menor em G2,0, acompanhada de maior TeO2 neste grupo. Concluiu-se que a perfusão global é prejudicada por concentrações maiores de isofluorano, ao passo que a perfusão periférica é mantida. Existe um limite para o grau de vasodilatação periférica causada pelo isofluorano em cães e o tempo de exposição ao anestésico interfere com a dinâmica cardiovascular tanto quanto sua concentração / The aim of this study was to evaluate the effects of isoflurane and anesthetic time period on tissue perfusion of dogs under two different concentrations. Eight beagle dogs were anesthetized in MAC multiples correspondent to 1.5 (G1.5) e 2.0 (G2.0) MAC for two hours, being the following variables collected every 20 minutes: heart rate (HR), arterial systolic (SAP), mean (MAP) and diastolic (DAP) pressures, pulmonary artery mean pressure (PAPm), pulmonary artery wedge pressure (PAWP), central venous pressure (CVP), cardiac index (CI), systolic index (SI), left ventricle work index (LVWI), total peripheral resistance index (TPRI), pulmonary vascular resistance index (PVRI), oxygen delivery index (IDO2), oxygen consumption index (IVO2), oxygen extraction (TeO2), mixed venous oxygen saturation (SvO2) and arterial blood lactate. Mean values of MAP, CI, SI and LVWI were different between groups, and such differences were not observed in TPRI and PVRI, which differences were only significant between time points in each group. In addition, there was progressive reduction of TPRI in G1.5, but not G2.0. There was a reduction of IDO2 in G2.0 when compared to G1.5, but not IVO2. Lactate levels were above reference limits, with no difference between groups and decreasing over time, whereas SvO2 was lower in G2.0, accompanied by higher TeO2 in that group. We conclude that global perfusion is impaired by higher concentrations of isoflurane, while peripheral perfusion is maintained. There is a limit to the degree of vasodilation caused by isoflurane in dogs and the time of exposure to the anesthetic interferes with cardiovascular dynamics as much as its concentrations

Class of 2017 Abstract / Objectives: Milk protein allergy is estimated to affect 1.2% to as much as 17% of people of all ages. Advair® Diskus® (FP/SX) utilizes lactose as an excipient which limits the utility of this product for this population. Furthermore, Advair® Diskus® is formulated as an interactive physical mixture via a micronization process. Alternatively, spray dried engineering achieves narrow particle size distribution, allowing greater deposition in the targeted respiratory bronchioles. The purpose of this dry powder inhaler (DPI) study was to conduct an in vitro comparative analysis of the aerodynamic performance of a co-spray dried lactose-free formulation of FP/SX with a mannitol excipient as a molecular mixture versus the Advair® Diskus® 250/50 (FP/SX) interactive physical mixture product. Methods: Utilizing mannitol as an excipient, a co-spray dried FP/SX powder was prepared using the Buchi Mini-Spray Dryer B-290 under closed system configuration. The resulting feed solution was spray dried at pump rates of 25%, 50%, and 100% with all other parameters remaining constant (aspiration, atomization rate, nitrogen gas rate). The primary outcome measure, aerodynamic performance, was assessed using the Copley Next-Generation Impactor (NGI). NGI data for the DPIs was used to calculate mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD), and fine particle fraction (FPF) of each powder, including the Advair® Diskus®. Residual water content was quantified by Karl Fischer titration. Particle characteristics were visualized by scanning electron microscopy. Results: FPF, MMAD, and GSD were calculated from NGI data; Wolfram Alpha software was used to calculate MMAD and GSD. T-test regression was used for comparative analysis of spray-dried and Advair® Diskus® powders. MMAD for each spray dried sample was analyzed using a t-test regression against the MMAD values from the Advair® Diskus®. Using aerodynamic analysis studies triplicated for each powder, there was no significant difference between the spray dried powder and Advair® Diskus® for MMAD and GSD (p-values >0.05). The 50% and 100% pump rate samples had similar FPF to the Advair® Diskus® (p-values >0.05). However, the 25% pump rate sample had a significantly improved FPF compared to the Advair® Diskus® (p <0.01). Conclusions: A co-spray-dried lactose-free formulation of FP/SX with a mannitol excipient demonstrated similar aerodynamic performance to the Advair® Diskus® which consists of a physical mixture of two drugs with lactose. Of significance, 25% pump rate spray-dry conditions demonstrated an improved FPF compared to the Advair® Diskus®.

Background: COPD is characterised by increased neutrophilic inflammation which further increases during exacerbations. Corticosteroids are currently one of the mainstays of treatment but they have limited effectiveness; there is a great need to develop new anti-inflammatory pharmacotherapies for use in COPD. Inhaled LPS has been used as a model of increased neutrophilic inflammation in healthy patients, smokers and asthmatics. Its use in patients with COPD as a model of exacerbations has not yet been evaluated. PI3 kinase is a vital intracellular enzyme, which upon activation leads to a number of cellular processes; the γ and δ isoforms of the enzyme are of particular importance in leucocyte migration, development and activation. There is increasing evidence for upregulation of this pathway in COPD.Aims: (1) To test the safety of the use of inhaled LPS in patients with COPD for use as a model of exacerbation and to investigate the systemic and airway inflammatory response in vivo. (2) To investigate the action of PI3 kinase enzyme inhibitors and dexamethasone in vitro on neutrophilic inflammation in COPD patients during the stable state and exacerbations. Methods: (1) 12 patients with mild to moderate COPD inhaled 5µg LPS; safety measurements and airway and systemic biomarkers were collected up to 24 hours post inhalation. (2) The effect of PI3 kinase enzyme inhibitors and dexamethasone on MMP-9 and ROS release from peripheral and airway neutrophils from stable COPD and exacerbations was examined in vitro. The effect of PI3 kinase enzyme inhibitors and dexamethasone on cytokine release from peripheral neutrophils from stable COPD patients was also investigated. Results: (1) Inhaled LPS (5µg) caused a significant fall in FEV1 and increase in sputum neutrophil numbers. There was an associated increase in systemic IL-6, CRP and CC-16, all with differing temporal patterns. No patients reported any significant symptoms. (2) PI3 kinase enzyme inhibitors significantly reduced MMP-9 and ROS release from airway and peripheral neutrophils from COPD patients in the stable state and during exacerbations; dexamethasone had minimal effect. Cytokine release from peripheral neutrophils from COPD patients in the stable state was also significantly inhibited by PI3 kinase enzyme inhibitors and dexamethasone. Conclusions: (1) Inhaled LPS in patients with COPD is a safe model to induce acute on chronic neutrophilic inflammation and therefore could be used as a model to study COPD exacerbations. (2) PI3 kinase enzyme inhibitors reduce COPD neutrophil MMP-9, ROS and cytokine release in vitro and are therefore are a promising new anti-inflammatory pharmacotherapy.

Outside to the wide range of potential benefits, the use of nanomaterials can endanger human health and the environment. This diploma thesis presents the results of pilot measurements, where the exposure of nanoparticles was monitored. Based on a literature research a suitable method for measurement was the three-stage OECD model. Based on this model, measurements were performed in three welding workplaces, where nanoparticles are produced incidentally. The measurement consisted of collecting information and measuring the concentration of nanoparticles in the workplace, where data collection was focused only on inhalation exposure. During welding, 0.3 m size particles are produced and their concentration is strongly influenced by the welding material, type of welding and suction. The particles are amorphous in terms of morphology and contain manganese, iron and silicon, which can cause neurodegenerative diseases. Furthermore, the results indicate the importance of monitoring oral exposure.