The application of a hollow waveguide (HW) was investigated as a gas cell for analytical infrared analysis. The analysis was the measurement of carbon monoxide (CO) and nitric oxide (NO) in sidestream cigarette smoke. An FT-IR analysis system was setup with a 3m multi-pass gas cell and a 55cm by 2mm i.d. Ag/AgI coated HW in tandem with individual CO and NO gas analyzers. The HW demonstrated response times an order of magnitude less than the larger volume multi-pass gas cell and slightly faster than the single analyte gas analyzer. Furthermore, it has been demonstrated that the HW provides up to approx. 60% greater sensitivity on a per meter optical path basis than the multi-pass gas cell of the analytes investigated due to increased optical efficiency maximizing the light concentration within the gaseous sample volume. Simulations in 3-D showed the sensitivity could theoretically improve by more than an order of magnitude if the IR beam was coupled more efficiently into the waveguide. Both FT-IR configurations gave statistically equivalent results for CO to the independent analyzers. With the HW increased temporal resolution, inter-puff measurements comparable to the gas analyzer were achieved at a lower spectral resolution. The HW optical configuration was modeled for ray tracing in MATLAB. Simulations in 2-D and 3-D were accomplished. The simulations show a major drawback to HW optimization is the coupling of the infrared beam into the waveguide. As demonstrated in a 3-D simulation, approximately 97% of the rays are rejected when an off-axis parabolic mirror with 25.4mm focal length is used to focus the IR beam into the 2mm i.d. waveguide. Repeating the simulation with longer focal length mirrors showed improved in IR coupling into the waveguide from 3% to 85%. Simulations applying a compound parabolic concentrator show comparable performance to the traditional design of two OAP mirrors to collect rays from the HW and focus onto the detector, but in a much smaller configuration. The simulation routines can be used to further improve the design of this and other optical sensing systems and enhanced by incorporating a spectral component to the simulation.

Thesis (Ph. D.)--Illinois State University, 1980. / Title from title page screen, viewed Feb. 17, 2005. Dissertation Committee: Herman Brockman (chair), Arlan Richardson, David Weber, Alan Katz, Brian Wilkinson. Includes bibliographical references (leaves 150-166) and abstract. Also available in print.

A gripe é causada pelo vírus Influenza e é um problema de saúde pública mundial, que pode levar a problemas sérios em idosos e crianças. O Brasil implantou a vacinação anual contra influenza a partir de 1999, como ação preventiva contra a doença. A vacina é produzida pelo Instituto Butantan e contém três cepas diferentes do vírus Influenza fragmentado para induzir resposta imune adaptativa, com produção de anticorpos específicos e neutralizantes. A literatura tem mostrado que a exposição à xenobióticos com potencial imunossupressor pode comprometer a eficácia de imunizações ativas, como a imunização contra a gripe. Nosso grupo de pesquisa tem mostrado que a exposição à hidroquinona (HQ), um composto tóxico presente em altas concentrações na fumaça do cigarro, prejudica a resposta imune inata e adquirida. Assim, este trabalho avaliou o efeito da exposição à HQ sobre a resposta imune à vacinação contra influenza. Camundongos machos da linhagem C57BL/6 foram diariamente expostos à HQ (2500 ppm) ou PBS, por 1 hora, por nebulização, por um período de 8 semanas. Durante este período, foram imunizados nas semanas 6 e 8 do início das exposições, pela injeção i.m. de 100µL da vacina. Os parâmetros tóxicos e imunológicos foram avaliados 7, 35 e 70 dias após a segunda dose da vacina. A exposição à HQ não alterou o peso corpóreo dos animais e nem causou alterações morfológicas no pulmão, fígado e rins (histologia por H&E); reduziu a frequência de hemácias (11%), hematócrito (14%), hemoglobina (14%) e volume celular (4%); causou estresse oxidativo no baço (citometria de fluxo); aumentou a área dos folículos de células B no baço e linfonodomegalia (histologia por H&E). Em conjunto, os dados aqui obtidos mostram que a exposição à HQ afetou mecanismos envolvidos na gênese da imunidade ativa contra influenza. Assim, os dados deste trabalho mostram mecanismos tóxicos ainda não descritos para a HQ, e ressalta a HQ como um poluente ambiental que deve ser considerado nas avaliações de risco. / The flu is a health problem worldwide which is caused by the Influenza virus and may result in severe illness in infants and the elderly. The annually vaccination against influenza was implemented in Brazil in 1999 as a preventive measure. The vaccine is produced by Butantan Institute and contains three different strains of the inactivated Influenza virus which induce the adaptive immune response along with production of specific and neutralizing antibodies. The literature has shown that exposure to immunosuppressive xenobiotics may compromise the efficacy of active immunizations, such as influenza. Our research group has shown that exposure to hydroquinone (HQ), a toxic constituent of cigarette smoke, impairs both innate and adaptive immune response. Thus, the aim of this work was to evaluate the effects of HQ on the immune response induced by the influenza vaccine. Male C57BL/6 mice were daily exposed to HQ (2500 ppm) or PBS by nebulization, for 1 hour, for 8 weeks. During the exposure period, the animals were vaccinated on weeks 6 and 8 with 100µL of the vaccine. Toxicologic and immunological parameters were assessed 7, 35 and 70 days after boost administration. HQ exposure did not alter body weight and did not cause morphological alterations in the lungs, liver and kidneys (H&E staining); reduced the frequency of erythrocytes (11%), hematocrit (14%), hemoglobin (14%) and cellular volume (4%) and caused oxidative stress on the spleen (Flow Cytometry); increased the area of B cell follicles in the spleen and increased the size of draining lymph nodes (H&E staining). Altogether, these data show that HQ exposure affected mechanisms involved in the genesis of the adaptive immune response. Thus, the data presented in this work show toxic mechanisms of HQ that have not yet been described, and it also points out HQ as an environmental pollutant which should be considered on risk assessments.

O anestésico local é o medicamento mais utilizado na Odontologia e sua associação com vasoconstrictores aumenta a duração da anestesia, diminuindo seus efeitos sistêmicos. A hipertensão e o tabagismo são freqüentes na população, sendo responsáveis por complicações sistêmicas. A felipressina, por não interferir com receptores simpáticos, poderia ser um vasoconstrictor indicado para pacientes hipertensos. O objetivo deste trabalho foi estudar a reatividade cardiovascular de animais simultaneamente hipertensos e fumantes passivos aos agentes vasoconstritores associados aos anestésicos locais, verificando também o efeito do tratamento com atenolol. Foram utilizados ratos Wistar machos, divididos em 5 grupos: 1) normotensos não fumantes; 2) normotensos fumantes passivos; 3) hipertensos não fumantes; 4) hipertensos fumantes passivos; 5) hipertensos fumantes passivos tratados com atenolol. A hipertensão renal foi induzida pela remoção do rim direito e instalação de clip de prata (abertura 0,25mm) na artéria renal esquerda, após anestesia com quetamina e xilazina. Os ratos fumantes passivos foram colocados diariamente por 10 minutos, durante 28 dias, em caixa de madeira de 30cmX25cmX15cm dividida em dois compartimentos. Em um deles, eram acesos 10 cigarros e no outro ficavam os animais. A tampa da caixa era fechada e um sistema de ventilação lançava fumaça dos cigarros para o compartimento dos ratos, num fluxo de 10l/min. Após medida indireta da pressão arterial, 14 dias após a cirurgia, o grupo tratado com atenolol foi medicado durante 14 dias seguintes (90 mg/Kg) por gavage. No 28o dia, todos receberam catéter de polietileno na artéria carótida esquerda (para medida de pressão) e outro na veia jugular direita (para injeção de drogas). Para os 5 grupos foram utilizadas: adrenalina (80, 160, 320, 640 e 1280ng) e felipressina (0,125, 0,25, 0,5, 1, 2 e 3 x 10-3UI). O catéter arterial era conectado a transdutor de pressão e o registro realizado por software específico. Foram analisadas: menor resposta hipotensora, maior resposta hipertensora e duração de resposta para cada dose. Os dados foram analisados por análise de variância de medidas repetidas, seguida do teste de Tuckey ou Holm-Sidack, com nível de significância de 5%. Os resultados mostraram que o fumo passivo reduziu significativamente a resposta vasodilatadora produzida pela adrenalina, em animais normotensos e hipertensos, potencializou suas respostas hipertensoras e aumentou a duração das respostas à adrenalina, ampliadas ainda mais pelo tratamento com atenolol. O tratamento com atenolol promoveu aumento adicional das respostas hipertensoras à adrenalina nos hipertensos-fumantes. A felipressina não apresentou ações vasodilatadoras e suas ações hipertensoras foram potencializadas pelo fumo passivo, em amplitude e duração. O atenolol não promoveu aumento adicional da amplitude das respostas à felipressina. Nos animais hipertensos, o tratamento com atenolol associado ao fumo passivo teve efeito expressivo, aumentando significativamente a duração total das respostas à felipressina. A felipressina, quando comparada à adrenalina, não apresentou efeitos hipotensores diretos, a resposta hipertensora máxima foi nitidamente inferior e a duração das respostas à felipressina foi o dobro da adrenalina. Dessa forma, a felipressina se torna uma droga interessante na hipertensão, devido a sua capacidade de promover vasoconstrição prolongada, sem potencializar a atividade simpática sistêmica. / The local anesthetic is the most common drug in dentistry and the associated vasoconstrictors increase the duration of anesthesia, decreasing its systemic effects. Hypertension and smoking are problems commonly found in the general population, being responsible for systemic complications. Felypressin, a vasoconstrictor that does not interact with sympathetic receptors, could be indicated to hypertensive patients. This study investigated the cardiovascular reactivity of hypertensive and passive smoker animals under atenolol treatment to epinephrine and felypressin. Male wistar rats were divided into five groups: 1) normotensive and non-smokers, 2) normotensive and passive smokers, 3) hypertensive and non-smokers, 4) hypertensive and passive smokers; 5) hypertensive, passive smokers and treated with atenolol. Renal hypertension was induced by removal of the right kidney and installation of a silver clip (with 0.25-mm opening) in the left renal artery, after anesthesia with ketamine and xylazine. The passive smoker rats were placed, 10 minutes per day, during 28 days in a 30cmX25cmX15cm wood box divided into two compartments. Ten cigarettes were lit in one compartment, and the rats were placed in the other. The box lid was closed and a ventilation system threw the cigarette smoke to the rat compartment. After indirect measurement of blood pressure, 14 days after the surgery, the group of rats treated with atenolol was medicated during the following fourteen days (90 mg/kg) by gavage. On the 28th day, a polyethylene catheter was inserted into the left carotid artery (for direct blood pressure measurements) and into the right jugular vein (for drug injection). The groups received epinephrine (80, 160, 320, 640 and 1280ng) or felypressin (0.125, 0.25, 0.5, 1, 2 and 3 x 10-3UI). The arterial catheter was connected to a pressure transducer and recording was made by a specific computer software. The following parameters were analyzed for all groups: lower hypotensive response, higher hypertensive response and duration of response for each dose. Data were statistically analyzed by repeated measures analysis of variance, followed by Tukey test or Holm-Sidack test, at a significance level of 5%. The results showed that passive smoking significantly decreased the vasodilator response produced by epinephrine in normotensive and hypertensive animals, increasing their hypertensive responses and increased the duration of response to epinephrine, that was further increased by atenolol treatment. Atenolol treatment increased the hypertensive responses in hypertensive-smokers rats. The felypressin did not show vasodilator responses and its hypertensive responses were increased by passive smoking. The atenolol did not cause additional increase in felypressin responses. In hypertensive animals, the atenolol treatment associated with passive smoking had expressive effects, significantly increasing the total duration of response to felypressin. Felypressin, when compared with epinephrine, did not show direct hypotensive effects, the higher hypertensive responses were smaller and the duration of response to felypressin was twice the epinephrine time. Then, felypressin becomes an interesting drug to hypertensive patients, due to its capacity to promote prolonged vasoconstrictor effect without increasing the sympathetic nerve activity.

Introduction. The adverse health effects of cigarette smoking are well established, including the direct effects of nicotine on human endothelial cells and fibroblasts. However, the direct effects of nicotine in the nasal cavity remain uninvestigated. The study aim was to ascertain the direct effect of chemical components in cigarette smoke on the microbial flora or microbiota of the nasal cavity. Methods. We enrolled 40 participants from the Benson Idahosa University’s Health clinics to conduct this study. Information on demographic characteristics including age, sex, and smoking duration was obtained at baseline. We collected nasal swabs of 20 smokers and 20 non-smokers. The wool content of the swap stick was immediately stored in mac Cathy bottles containing 9 ml of normal saline and transported to the laboratory in less than 45 minutes after collection for microbiological analysis under aseptic condition. The enumeration of the microorganisms was carried out using the streak and pours plate method on Nutrient agar, Blood agar, Chocolate agar, Mac coney agar and Potato Dextrose agar (PDA). A two-sample t-test was used to determine differences in enumeration of microorganisms and isolates between smokers and non-smokers. Results. Total bacterial counts for the smokers ranged from 177 - 307 x 102 cfu/ml and 223 - 551 x 102 cfu/ml for non-smokers with (p = 0.046 Nutrient agar, and p = 0.011 PDA). The bacteria isolates were identified as Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, Proteus vulgaris and Streptococcus pneumonia, and the fungi isolates were identified as Aspergillus niger, Rhizopus stolonifer, Tricoderma viridae, respectively. The mean of nutrient agar in smokers is significantly lower (12.10) than that in nonsmokers (19.35), and the mean of PDA in smokers is significantly higher in smokers (5.75) than in nonsmokers (2.35). Higher percentages of gram-negative rods including Klebsiella pneumoniae (20%), Escherichia coli (20%) and Proteus vulgaris (20%) were identified in the smokers, which is in contrast to higher percentage of gram-positive cocci including Staphylococcus aureus and Streptococcus pneumonia identified in non-smokers. The most commonly isolated fungus in smokers was Aspergillus niger (45%) and nonsmokers was Rhizopus stolonifer (60%). Conclusions. Study findings demonstrated increased bacterial count and isolates in nasal cavity of smokers than non-smokers. Future studies should be warranted to understand the mechanistic role of nicotine in influencing microbiota of the nasal cavity.

Use of electronic cigarettes (e-cigarettes) is rapidly growing around the world. E-cigarettes are commonly used as an alternative nicotine delivery system, and have been advocated as generating lower levels of harmful chemicals compared to conventional cigarettes. Cigarette smoke-like aerosols are generated when e-cigarettes heat e-liquids. The main components of e-cigarette liquids are propylene glycol (PG) and glycerol (GL) in a varying ratio, plus nicotine and flavor chemicals. Both PG and GL are considered safe to ingest in foods and beverages, but the toxicity of these chemicals in aerosols is unknown. Current studies of e-cigarettes have mainly focused on dehydration and oxidation products of PG and GL. In this study, the other degradation products that can be generated during the vaping process are discussed. In addition, the gas/particle partitioning of chemicals in vaping aerosols is determined. This work finds that the formation of benzene in electronic cigarettes depends on the wattage, types of coils, and devices. To simulate commerical e-cigarette liquids, mixtures containing equal parts of PG and GL by volume were made with the following added components: benzoic acid (BA), benzoic acid with nicotine (Nic), benzaldehyde (BZ), band enzaldehyde with nicotine. PG only, GL only, and PG and GL mixtures were also made for comparison. The data presented here demonstrate that more benzene is generated as the wattage of a device increases. The results also seem to support the importance of ventilation in the generation of benzene. More benzene is generated from the mixtures containing benzoic acid when using the EVOD device with a smaller vent. However, benzaldehyde yields more benzene when using the Subtank Nano device with a larger vent. Findings also indicate that more benzene is produced from GL rather than PG. This thesis also addresses the chemical formation pathways of degradation compounds found in the aerosols formed from isotopically labeled e-cigarette liquids. Mixtures of both 13C-labeled and unlabeled PG as well as GL were made. The mixtures were vaped and gas-phase samples were collected to determine which chemicals were in the gas-phase portion of the aerosols. With the use of GC/MS methods, these isotopic labeling experiments provided evidence that the majority of the benzene, acetaldehyde, 2,3-butanedione, toluene, xylene, acrolein, and furan found in e-cigarette aerosols originates from GL in the PG plus GL mixtures. It was also shown that the majority of propanal is derived from PG: while hydroxyacetone can be formed from both PG and GL. Possible mechanisms for the formation of acetaldehyde, benzene, 2,3-butanedione, toluene, and xylene formation are proposed. Last, this study investigated the gas/particle partitioning of nicotine and flavor-related chemicals in e-cigarette fluids. The gas/particle partitioning behavior of chemicals in e-cigarettes fluids is highly dependent on the chemical volatility. A total of 37 compounds were examined. The target compounds were divided into 3 groups based on their vapor pressures: high, medium, and low. Headspace gas samples were collected and analyzed to determine the concentration of a compound in equilibrium with the liquid phase. The gas and liquid concentrations were used to calculate the gas/particle partitioning constant (Kp) for each compound. In an e-cigarette aerosol, volatile compounds have smaller Kp values and tend to be found in greater proportion in the gas-phase, whereas the less volatile compounds are likely to stay in the particle phase. General agreement with theory was found for compounds with known activity coefficients in PG and GL, indicating that theory can be used to predict Kp values for other compounds.

ABSTRACT Background: Asthma is a chronic lung disease that inflames and narrows the airways. This results in recurrent episodes of coughing, wheezing, shortness of breath, and chest tightness. Although the causes of asthma are poorly understood, genetic and environmental factors have been implicated in the development and exacerbation of the disease. Among environmental risk factors, cigarette smoke is a well-known risk factor to trigger asthma symptoms. Exposure to secondhand smoke irritates the airways and may trigger an attack in adults with asthma. Smoke-free laws and regulations in the United States differ by state. The enforcement of smoke-free legislation has been related to asthma rates as it has been shown that they lead to a sustained drop in emergency hospital admission for asthma among adults. These laws and regulations are also necessary in reducing smoking rate and secondhand smoke exposure. Objective: The purpose of this thesis is to examine the association between tobacco smoke rates and asthma status among adults at the national and state levels and to evaluate the effects of state smoke-free laws and regulations on tobacco smoking rate among adults with asthma. Methods: The Centers for Disease Control and Prevention’s 2009–2010 Behavioral Risk Factor Surveillance System data was used for the analyses. SAS-callable SUDAAN (version 10.0.0, RTI International, NC) was utilized to account for the complex sampling design of the BRFSS, and sample weights were used to produce estimates that were generalizable to the state and U.S. adult population. In addition to calculating descriptive statistics, chi-square tests and multivariate logistic regression were used to test for group differences and association between variables of interest. State level smoking rates were ranked to identify states that are in the lower and upper 20th percentiles and compare them with states’ smoke-free laws and regulation status. Results were considered significantly different if 95% confidence intervals (CIs) did not overlap or if statistical testing at p<0.05 was applicable. Results: Asthma prevalence rates are higher among adults that smoke cigarettes (10.5%, [aPR] =1.2) compared to non-smokers (7.8%, [aPR] =1.0). Of the 869,519 adult respondents in the survey, 8.5% reported having asthma. Nearly one-fifth (17.2%) of adults without asthma smoked cigarettes, while (21.7 %) of adults with asthma smoked. Females (10.5%) had higher asthma prevalence rates than males (6.4%). Black persons (10.0%), persons of American Indian (13.0%) descent had higher, and those of Hispanic (6.7%) descent had lower asthma rates than white persons (8.6%). Adults with a high school education or less (9.1%) had higher asthma rates than those with an education level that was equivalent to a 4 year college or more (7.3%) , and those with low income (<$15,000) had higher rates (13.3%) than those with high income (6.8%). Percentage of male (23.4%) and females (20.7%) with asthma who smoke are higher than those that do not smoke (19.3% and 15.1%, respectively). Asthma prevalence rates and smoking rates vary by geographic location. Smoking rates among adults with asthma was highest in the South (LA, AL, SC, TN, OK, MS, AR, WV, KY) and a couple of Midwest states (OH, IN,). Evaluating the association between the 2008 State of Tobacco Control Report and smoking rate among adults with asthma by state showed a statistically significant relationship between smoking rate among adults with asthma and smoke-free policy and regulation at the state and national level. On average, states with the lowest smoking rate among persons with asthma (smoking rates less than 20th percentile) had significantly higher smoke-free policy grades (mean grade [sd]=7.2 [1.99]) than states with a high smoking rate (smoking rate of 80th percentile or more) (mean grade [sd]=2.0 [2.00]) (p-value < 0.00001). Conclusion: Although most U.S. state smoke-free policies and regulations are relatively new, it is evident that these laws are effective in promoting cessation among adults and reducing nonsmokers’ exposure to secondhand smoke. The study found that smoke-free laws may improve health by lowering asthma prevalence and smoking rates among adult smokers. Also, these policies in turn protect non-smokers from the harmful health effects of secondhand smoke.

published_or_final_version / abstract / toc / Pharmacology / Doctoral / Doctor of Philosophy

published_or_final_version / Pharmacology / Doctoral / Doctor of Philosophy

Thesis (M.S.)--West Virginia University, 1999. / Title from document title page. Document formatted into pages; contains xi, 107 p. : ill. (some col.) Includes abstract. Includes bibliographical references (p. 98-107).